Progress in Physical Organic Chemistry, Volume 10

Progress in Physical Organic Chemistry, Volume 10 Editors Andrew Streitwieser, Jr. Robert W. Taft JOHN WILEY & SONS P...

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Progress in Physical Organic Chemistry, Volume 10

Editors Andrew Streitwieser, Jr. Robert W. Taft JOHN WILEY & SONS

Progress in

PHYSICAL ORGANIC CHEMISTRY VOLUME 10

Progress in

PHYSICAL ORGANIC

CHEMISTRY VOLUME 10

Editors

ANDREW STREITWIESER JR.,

Department of Chemistry University of California, Berkeley, California

ROBERT W. TAFT, Department of Chemistry University of GIifornia, frvine, California

1973 A N INTE RSCIEN CE@ P U B L I C ~ T I ON

JOHN WILEY &SONS,

New York

London

*

Sydney

Toronto

An Interscience@ Publication Copyright 0 1973, by John Wiley & Sons, Inc. All rights reserved. Published simultaneously in Canada.

No part of this book may be reproduced by any means, nor transmitted, nor translated into a machine language without t k written permission of the publisher.

Library of Congress Catalog Card Number: 63-19364 ISBN 0-471-83356-8 Printed in the United States of America 1 0 9 8 7 6 5 4 3 2 1

Introduction to the Series

Physical organic chemistry is a relatively modern field with deep roots in chemistry. The subject is concerned with investigations of organic chemistry by quantitative and mathematical methods. The wedding of physical and organic chemistry has provided a remarkable source of inspiration for both of these classical areas of chemical endeavor. Further, the potential for new developments resulting from this union appears to be still greater. A closening of ties with all aspects of molecular structure and spectroscopy is clearly anticipated. The field provides the proving ground for the development of basic tools for investigations in the areas of molecular biology and biophysics. The subject has an inherent association with phenomena in the condensed phase and thereby with the theories of this state of matter. The chief directions of the field are: (a) the effects of structure and environment on reaction rates and equilibria; (b) mechanism of reactions; and (c) applications of statistical and quantum mechanics to organic compounds and reactions. Taken broadly, of course, much of chemistry lies within these confines. The dominant theme that characterizes this field is the emphasis on interpretation and understanding which permits the effective practice of organic chemistry. The field gains its momentum from the application of basic theories and methods of physical chemistry to the broad areas of knowledge of organic reactions and organic structural theory. The nearly inexhaustible diversity of organic structures permits detailed and systematic investigations which have no peer. The reactions of complex natural products have contributed to the development of theories of physical organic chemistry, and, in turn, these theories have ultimately provided great aid to the elucidation of structures of natural products. Fundamental advances are offered by the knowledge of energy states and their electronic distributions in organic compounds and the relationship of these to reaction mechanisms. The development, for example, of even an empirical and approximate general scheme for the estimation of activation energies would indeed be most notable. The complexity of even the simplest organic compounds in terms of physical theory well endows the field of physical organic chemistry with the frustrations of approximations. The quantitative correlations employed in this field vary from purely empirical operational formulations to the approach of applying physical principles to a workable model. The most common procedures V

vi

INTRODUCTION TO THE S1:RIHS

have involved the application of approximate theories to approximate models. Critical assessment of the scope and limitations of these approximate applications of theory leads to further development and understanding. Although he may wish t o be a disclaimer, the physical organic chemist attempts to compensate his lack of physical rigor by the vigor of this efforts. There has indeed been recently a great outpouring of work in this field. We believe that a forum for exchange of views and for critical and authoritative reviews of topics is an essential need of this field. It is our hope that the projected periodical series of volumes under this title will help serve this need. The general organization and character of the scholarly presentations of our series will correspond to that of the several prototypes, e.g., Advances in Enzymology, Advances in Chemical Physics, and Progress in Inorganic Chemistry. We have encouraged the authors to review topics in a style that is not only somewhat more speculative in character but which is also more detailed than presentations normally found in textbooks. Appropriate to this quantitative aspect of organic chemistry, authors have also been encouraged in the citation of numerical data. It is intended that these volumes will find wide use among graduate students as well as practicing organic chemists who are not necessarily expert in the field of these special topics. Aside from these rather obvious considerations, the emphasis in each chapter is the personal ideas of the author. We wish to express our gratitude to the authors for the excellence of their individual presentations. We greatly welcome comments and suggestions on any aspect of these volumes. ANDREWSTREITWIESER, JR. ROBERTW. TAFT

Contents

A Generalized Treatment of Substituent Effects in Benzene Series. A Statistical Analysis by the Dual Substituent Parameter Equation. BY S. EHR E N SO N , Department of Chemistrv, Brookhaven National Laboratory, Upton, Long Island, New York; R. T. C. BROWNLEE, Department of Chemistry, La Trobe University, Bundowa, Victoria, Australia; R. W. TAFT,Department of Chemistry, University of California, Irvine, California . . . . . . . . . . . . 1 Substituent Effects in Nonaromatic Unsaturated Systems. BY M. C H A R T O N , Department of Chemistry, Pratt Institute, Brooklyn, NewYork . . . . . . . . . . . . . . . . . 81 Vinyl and Allenyl Cations. BY P. J. S T A N G , Department of Chemistry, . . . . . 205 The University o f Utah, Salt Lake City, Utah Physical Properties and Reactivity of Radicals. BY R. Z A HR A D N I K A N D P. C A R S K Y , Institute of Physical Chemistry, Czechoslovak . . . . . 327 Academy of Sciences, Prague, Czechoslavakia Probing the Active Sites of Enzymes with Conformationally Restricted Substrate Analogs. BY G. L. K E N Y O NA N D J. A. FEE, Department of Chemistry, University o,f California, Berkeley, California . 381 The Enthalpy-Enthropy Relationship. BY 0. E X N E R , J. Heyrovsky Institute of Polarography, Czechslovak Academy of Sciences, Prague, . . . . . . . . . . . . . . . 41 1 Czechoslovakia Author Index

. . . . . . . . . . . . . . . . . 483

Subject Index

. . . . . . . . . . . . . . . . . 501

Cumulative Index,Volumes 1-10

. . . . . . . . . . 505

vii

Progress in

PHYSICAL ORGANIC CHEMISTRY VOLUME 10

A Generalized Treatment of Substituent Effects in the Benzene Series. A Statistical Analysis by the Dual Substituent Parameter Equation ( 1 ) By S . Ehrenson. R . T . C . Brownlee. and R . W . Taft Contribution from the Brookhaven National Laboratory. Upton. N e w York. 11973. and the Department of Chemistry. University of California. Irvine. California. 92664

CONTENTS

I.

I1.

I11.

IV.

Introduction . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . A . U R (BA type) Values . . . . . . . . . . . B. ak (A type) Values . . . . . . . . . . . . C. &Values . . . . . . . . . . . . . . D . rn-Substituent Effects . . . . . . . . . . . E . uk Values . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . A . Regarding Fittings by Equation ( I ) . . . . . . . B . Pi Delocalization Parameters and their Interpretations . . 1. The u& Scale . . . . . . . . . . . . 2. The OR(BA) Scale . . . . . . . . . . . 3 . The u k Scale . . . . . . . . . . . . . 4. T h e o k Scale . . . . . . . . . . . . . C. ConcerningoR TypeandValuesofthepR Parameter . . D . Concerning the Separation of I and R Effects . . . . E . Variables Affecting h . . . . . . . . . . . F . Ionization of Phenols in Water . . . . . . . . G. Regarding Independent Generation of or and uR Parameters H . “Secondary” OR Values . . . . . . . . . . I . Additional Applications . . . . . . . . . . J . Solvent Effects on pinand pfin Benzoic Acid Ionization . K . Ortho Substituent Effects . . . . . . . . . . Summary . . . . . . . . . . . . . . Acknowledgement . . . . . . . . . . . . References . . . . . . . . . . . . . .

I

. . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . .

.

. . . . . . . . . . .

.

. .

. . . . .

. . . . .

. . . . . . . . . .

. . . . .

2 4 4 13 20 28 31 35 35 39 42 42 43 43 44 47 48 50 53 53 55 59 59 64 78 78

2

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

I. INTRODUCTION In this chapter, we report the results of a critical statistical reexamination of substituent effects in the benzene series (2). This investigation has uncovered new basic facts in support of both traditional and new insights. Of particular importance is the demonstration that a practical means of correlation may be achieved for data of a very broad scope with retention of relatively high precision. The treatment is presented in full and applications and their significances are discussed. The thrust of the argument is based upon the fact that no classes of substituents have been arbitrarily neglected: i.e., conclusions are drawn from data sets containing a full range of substituent electronic properties. The analysis of substituent effects in the naphthalene series was carried out along similar lines (2p) and served to prompt this reexamination of the benzene series data. The dual substituent parameter treatment attributes substituent effects to an additive blend of polar (Z) and pi delocalization ( R ) effects, each of which may be represented as a up product (3): log(k/k&, or other substituent property,P=Ii+Ri=urd+oRpk.

(1)

4

The susceptibility or mixing coefficients, and pk, depend upon the position of the substituent (indicated by the index, i) with respect to the reaction (or detector) center, the nature of the measurement at this center, and the conditions of solvent and temperature. It has been held that the qscale of polar effects has wide general applicability (4), holding for substituents bonded to an sp2 or sp3 carbon atom ( 5 ) and, perhaps, to other elements (6). The UR scale, however, has been thought to be more narrowly defined (7), holding with precision only for systems of analogous pi electronic frameworks (i.e., having a dependence on reaction type and conditions, as well as on position of substitution). The limits of eq. (1) may be represented as follows:

P' urpi, -+

as x

-+

O

and

P

-+

u R p i , as X

-+

w,

where X

pR/pI

Several approximately characterized values of single substituent parameter treatments are defined by finite values of A: i.e.,

u(,,,) -tP/pi, as A

-+

.4

U -( P~) o ~ + - + P /ap s hi ,- + 1.0

Swain and Lupton (2q) have recently presented a modified form of the dual substituent parameter treatment. In this treatment, the ur parameters were

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

3

adopted but placed on a readjusted scale. A single universal scale of resonance or pi delocalization parameter ( R ) was proposed which is claimed t o have equal or nearly equal precision of fit when applied generally. This latter proposal runs contrary to earlier thought (2e, f ) and, indeed, clearly is not supported by the present critical analysis. Specifically, statistical evidence is presented herein which supports the basis for at least four distinct scales of pi delocalization effects (u:, O R ,u; , and u i ) , each of which gives excellent precision within “limited generality.” The utility of these scales in discriminating between reaction types, transition-state structures, and reaction conditions is demonstrated and applications are discussed in this and in subsequent papers of the series. Experience has shown that correlations of good precision are those for which SD/RMS = f Q . l , where SD is the root mean square of the deviations and Rh4S is the root mean square of the data P i s . SD is a measure equal to, or approaching in the limit, the standard deviation in parameter predetermined statistics, where a large number of data points determine a small number of parameters. In a few series, RMS is so small that even though SD appears acceptable, f values do exceed . l . Such sets are of little significance pro or can. Evidence has been presented (2p) that this simple f measure of statistical precision is more trustworthy in measuring the precision of structure-reactivity correlations than is the more conventional correlation coefficient. When comparisons are to be drawn among scales derived with different criteria of physical validity, we believe this point to be especially appropriate. The SD is the explicit variable in the least-squares procedure, after all, while the correlation coefficient is a deriva!ive providing at best a non linear acceptability scale, with good and bad correlations often crowded in the range .9-1.0. The present work further provides strong confirmation of this conclusion. A valid UR scale (by our criteria) is one that on application of eq. (1) meets the condition f Q .I in a generalized manner not realized by other scales. A factor of two or greater in the SD for a reaction series (for f values greater than .03)is considered a particularly significant difference. Both the numbers and kinds of substituent data within a series are especially critical. For defining OR scales, we have considered only series data for which at a given position (ortho, meta, or para) the following substituents are available: N(CH&, NH2, or OCH3 (any two of these); any two t R substituents (CF3, C02R, CH3C0, CN, NO2); H and CH3 (both); any two halogens (but not both C1 and Br). This minimal basis set is required to minimize real or accidental correlations between substituent q and UR values. Such a minimal basis set offers substantial assurance of a critical analysis by eq. (1). Application of eq. (1) to series data containing less than the minimal basis set can be subject to uncertainty, if indeed not totally misleading results, depending upon the adequacy of the substituents included. We believe this important limitation has not been adequately recognized in previous treatments.

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

4

11. RESULTS

A. OR (BA type) Values The ionization of benzoic acids in water at 25" was used by Hammett as the standard reaction for the original crp treatment (2a). This reaction and several analogous reactions, e.g., ionization and ester saponification rates of benzoic acids, cinnamic acids, and phenylpropiolic acids, gives up correlations of relatively high precision. Taft and Lewis classified such reactions in an A category (20. Reexamination of these A reactions, as well as additional analogous data which have become available subsequently, provided eight reaction series of data of apparently comparable reliability. In the para position, each of these sets of data meets the necessary condition of a minimal basis set TABLE I Values of

UI

UI

and UR(BA) aR (BA)

n

- .83

6 8 6 8 2 3 8

~

-N(CH 3 ) 2 -NH, -NHCOCH, -OCH, -OC,H, -SCH, -CH -C€.H, -F -c1 -Br -1

-H -Si(CH J, -SOCH, -scF', -SOU -SF,

-CF, -SO,CH -CO,R -CN -NO, -COCH,

.06 .12 .26 .21 .38 .23 -.04 .10

.so .46 .44 .39

.oo -.lo

-.82 -.36 -.61

-.55a -.32 -.11 -.11 -.45 -.23 -.19 -.16

.oo .06

SO

.oo

.42 .64

.04 .08 .06 .08 .I 2 .14 .13 .15 .16

.51

.45 .59 .30 .56 .65 .28

a Value defined by reaction 8 only, cj: discussion

4 1 8 1 6 8 3 3 1 1 1

3 4 6 8 8 5

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

5

(temperature variation alone has not been considered a sufficient condition for distinguishing separate reaction series). The para substituent effect data for these eight reactions were best fitted to eq. (1) by full least-squares methods (21) to generate the “best” OR values for the benzoic acid (BA) type. The statistical methods described previously (21) have been used throughout this study. In addition to eq. (l), the following conditions were imposed upon these data: (a) the q s e t given in Table I (8); (b) the standard (classical) reaction conditions pf’ = pfi = 1.OOO for reaction 1 , the ionization of benzoic acids in water at 25” (note that h = 1.OOO was not imposed on any reaction series other than 1). With these constraints, a set of UR(BA) parameters was obtained for optimum fits to the eight basis sets of data (SD = .039 or 5% of RMS = .73 for 116 data points). It was found, however, that there was no serious loss in precision if certain UR(BA) parameters were modified by .01 to .03 units in order to keep invariance of parameters, if possible, among all of the OR scales of Table V. This modified set of UR ( B A ) was adopted as listed in Table I. The eight basis sets are fitted with the parameters of Table I to SD = .043, or 6% of RMS. Table I1 lists the values of pf, p i , hp = /&, n, SD, and f obtained with Table I parameters for each of the eight reactions. All neutral substituents were treated for which a urvalue was available from at least one aliphatic series reaction and a log (KP/Ko)value for one of the basis set reaction series. The final figure given in Table I1 is the p value obtained from the Hammett u values listed by Richie and Sager (2m) (from the single substituent parameter treatment). The maximum uncertainty in the UR values of Table I is estimated to be k.02 from the ratio of the SD of fit to the RMS of PR values of Table 11. Data for other p-substituted benzene side-chain reactions are fitted by eq. (1) using the UI and OR values of Table I with widely varying precision measures. However, precision of fit comparable to that achieved for the eight basis set reactions of Table I1 is obtained (only) with recognizable analogs of the para BA type. Other reaction types are fitted generally with values of f=SD/RMS greater by factors of two or more than the -6% level achieved by the para BA type (cf. subsequent Tables VII, IX, XII, XIV). In Table 111 are shown values of p f , p$ , hP, n, SD, f and Hammett p values obtained for additional para BA type reaction series which contain data for sufficient numbers ( n ) and kinds of substituents to provide a reasonably critical analysis. We d o not believe, however, that the analysis is as critical for sets which d o not meet the minimal requirements for a basis set. The reaction series are segregated according to type of measurement: equilibrium, rate, and fluorine nmr (F-nmr) shift. Any data set in Table I11 and in all tables hereafter (other than designated basis sets) which meets our minimal basis set criterion is indicated by an asterisk.

PI

OI

Reaction

1.355

1.976 2.222

.84

1.440

1.717

2.539

.75

1.311

1.750

.87

.69 16

9

14

14

10

.87

.947

1.084

14

20 19

n

.79

1.213

1.536

I .O1 .8 I

AP

1.003 1.272

P!4

,997 1.564

P';

.O 3

.04

.032

.047

,073

.052

.04 .06

.058

.03

2.364

I .798

1.589

1.503

1.045

1.359

.038

.02

P

1.002 1.407

P . I 19 .064

.05 .05

SD

1. (a) McDaniel, D. H., and H. C. Brown, J. Org. Chem., 23, 420 (1958); (b) Fischer, A,, B. R. Mann, and J. Vaughan,J. Chem. SOC.,1093 (1961). 2. (a) Roberts, J. D., et al., J. Am. Chem. SOC., 71, 2923 (1949); 72, 408, 628 (1950); 73, 2181 (1951); 75, 2267 (1953);(b) Bordwell, F. C., et ol., J. Am. Chem. SOC., 74, 1058 (1952); 78, 854 (1956); 79, 717 (1957); (c) Fawcett, F. S., and W. A. Sheppard,J. Am. Chem. Soc., 87, 4341 (1965); (d) Sheppard, W. A., J. Am. Chem. Soc., 84,3072 (1962); 85, 1314 (1963); 87, 2410 (1965);(e) Exner, O., and J. Lakomy, Coll. Czech. Chem. Commun., 35, 137 (1970). 3. Wepster, B. M., private communication. 4. Wepster, B. M., private communication. 5. Wepster, B. M.,private communication. 6. (a) Simon, W.,A. Morihofer, and E. Heilbronner, Helv. Chim. Act., 40, 1918 (1957); (b) Exner, O., and I. Jonas, Coll. Czech. Chem. Commun.,27, 2296 (1962); (c) Exner, O., Coll. Czech. Chem. Commun., 31, 65 (1966); (d) Kolfus, K., M. Vecera, and 0. Exner, Coll. Czech. Chem. Commun., 35, 1195 (1970); (e) Exner, O., and I. Lakomy, Coll. Czech. Chem. Commun.,35, 1371 (1970). 7. Davis, M.M., and H. B. Hetzer, J. Res. Natl. Bur. Standards, 60, 569 (1958). 8. (a) cf. Jaffk, H. H., Chem. Revs., 53, 198 (1953); (b) Berliner, E., M. C. Beckett, E. A. Bloomers, and B. Newmm, J. Am. Chem. Soc., 74, 4940 (1952).

I . Ionization, ArCO,H, H,O, 25" 2. Ionization, ArCO,H, 50% aq. EtOH, 25" (R) 3. Ionization, ArCO,H, 50% aq. EtOH, 25" (W) 4. Ionization, ArCO,H, 10%aq. EtOH, 25" 5. Ionization, ArCO,H, 75% aq. EtOH, 25" 6. Ionization, ArCO,H, 80% aq. Me cellosolve, 25" 7. Ion-pair formation, ArC0,H with 1,3-DPG,benzene 25" 8. Rate, saponification, ArC0,Et 60% aq. acetone, 25"

No.

Basis Sets for UR(BA type) Values

TABLE 11

rl

Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization, Ionization,

\

26. Saponification, ArCO,Et, 88% aq. EtOH, 30" 27. Esterification, ArCO,C,,H,,, (-OMe), MeOH, 40"

AI-N-N

N, ethylene glycol,

I//

I

Reaction

ArCO,H, 43.5% dioxane -H,O, 25" ArCO,H, 73.5% dioxane -H,O, 25" ArCO,H, ethylene glycol, 25" ArCO,H, MeOH, 25" ArCO,H, EtOH, 25" ArCO,H, n-PrOH, 25" ArCO,H, n-BuOH, 25" ArSO,NH,, H,O, 20" ArSO,NHC,H,, H,O, 20" ArAs(OH),O; H,O, 22" ArSe(OH),, H,O, 25" A r c s - C O , H , 50% aq. EtOH, 25" A r M - C O , H , 35% aq. dioxane, 25" trans-ArCH=CHCO,H, H,O, 25" cis-ArCH=CHCO,H, 50%aq. EtOH, 25" 2-MeArCO2H, 50% aq. EtOH, 25" H,N-C=N

25. Rearrangement, 194O

9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

No.

2.602 2.578

1.371

1.426 1.525 1.247 1.358 1.535 1SO5 1.486 1.078 1.140 .898 1.068 .694 .721 .450 .810 1.656

Pf)

2.307 2.212

Rates

1.178

1.153 1.241 1.044 1.139 1.182 1.227 1.217 .872 .943 .683 .812 .664 .687 .439 .643 1.594

Equilibria

P%

.89 .86

.86

.8 1 .81 .84 .84 .77 .82 .82 .81 .83 .76 .76 .96 .95 .97 .79 .96

AP

.04 .06 .03 .07

5 7 4 5 4 5 5

11 6

5

.05

5

.06 .02

.03

.05

.02

.05

.02 .02 .02 .03 .02 .03 .01 .03

SD

7 7 8 8 8 7 7 6

n

Benzoic Acid Type Series. Fits to Eq. (1) with Use of UR(BA) Values

TABLE 111

,072 .013

.041

,030 .050 .027 .075 .087 .lo6 .I54 .08 1 .217 .258 .05 8 .059

.050

.040 .04 1 .044

J'

2.593 2.608

1.310

I .453 1.556 1.269 1.382 1.545 1.531 1.514 .997 1.062 .827 .961 .712 .731 .470 .794 1.702

P

Reaction 0

, 15% aq. EtOH,

-2.710 16.811 4.400 -3.315 -5.651

F-nrnr Shifts

1.06 1.81 1.40 1.03 1.32

.94 .45 .89 1.04 -.37 .93 .74

2.925 ,112 -2.302 -2.404 .I94 243 .296

3.107 ,250 -2.576 -2.316 - .527 .902 .403

-2.549 9.297 3.148 -3.225 -4.279

.96

1.10

hP

1.268

1.931

Pa

1.317

1.761

4

.03 .03

9 7 4 8 5

.065 .070

.I 10 .035

.07 .35 .15

.18 .07

.059

.157

.169 .064

.05

6 10 6

5 5

.021 ,274 .055 .030

.03 .03 .06 .03 4 7

.065

f

.076

.06

SD

.04

8

8

n

-2.605 1 1.28 3.892 -3.370 -4.446

3.177 . I 84 -2.61 8 -2.441 - .396 ,912 .327

1.361

1.942

P

9. Elliott, J. H., and M. Kilpatrick, J. Phys. Chem., 45, 485 (1941). 10. (a) Elliott, J. H., and M. Kilpatrick, J. Phys. Chem., 45, 485 (1941); (b) Kilpatrick, M., Chem. Revs.,30, 159 (1942). 11. (a) Elliott, J. H., and M . Kilpatrick,J. Phys. Chem., 45, 472 (1941); (b) Kilpatrick, M., and R. D. Eanes,J. Am. Chem. Soc., 65, 589 (1943); (c) Kilpatrick, M., Chem. Revs., 30, 159 (1942). 12. (a) Elliott, J. H., and M. Kilpatrick, J. Phys. Chem., 45, 454 (1941); (b) References (b) and (c) for set no. 1 1 .

*37. ArCOC,H,F@), CH2C1,, 25" 38. ArCH,F, CCI, 39. ArSF, (apex), CC1, 40. ArC,H,F@), benzene or DMF 41. ArSC,H,F@), CH,C12 ,25"

CH 29. Saponification, trans-ArCH=CHCO,Et, 88% aq. EtOH, 30" 30. Hydrolysis, (ArCO),CO, 75% aq. dioxane, 58" 31. Thermal decomposition, ArCO,Et, 515" 32. Solvolysis, ArSCH,CI, 50% aq. dioxane, 35" 33. Decomposition, ArCONOCOC,H;K+, H,O, 30" 34. Esterification, ArCO,H, (HCl), MeOH, 25" 35. Reaction, ArCO,H, DPDM, EtOH, 30" 36. Reaction, rrans-ArCH=CHCO,H, DPDM, EtOH, 35"

28. Saponification, X25"

No.

TABLE 111 (continued)

W

13. (a) Elliott, J. H., and M. Kilpatrick, J. Phys. Chem., 45, 466 (1941); (b) References (b) and (c) for set no. 1I . 14. (a) Elliott, J. H., J. Phys. Chem., 46, 221 ( I 942); (b) Reference (c) for set no. 11. 15. References (a) and (c) for set no. 1 1 . 16. Willi, A. V., Helv. Chim. Acta, 3 9 , 4 6 (1956). 17. Reference for set no. 16. 18. Pressman, D., and D. H. Brown, J. Am. Chem. SOC., 65, 540 (1943). 19. Gould, E. D., and J. D. McUllough,J. Am. Chem. SOC.,71, 674 (1949); 73, 1109 (1951). 20. Benghist, I., and E. I. Becker,J. Org. Chem., 23, 885 (1958). 21. (a) Newman, M. S., and S. H. Merrill, J. Am. Chem. SOC.,77, 5552 (1955); (b) Soioman, I. J., and R. Filler,J. Am. Chem. SOC.,85, 3492 (1963). 22. Dippy, J. G., and J. E. Page,J. Chem. SOC.,357 (1938). 23. Fuchs, R., and J. J. Bloomfield, J. Org. Chem., 31, 3423 (1966). 24. Roberts, J. D., and J. A. Yancey,J. Am. Chem. SOC., 73, 1012 (1951). 25. Henry, R. A., W. G. Finnegan, and E. Leibler, J. Am. Chem. SOC.,76, 88 (1954). 26. (a) cf. JaffB, H. H., Chem. Revs., 53, 198 (1953); (b) Berliner, E., M. C. Beckett, E. A. Bloomers, and B. Newman, J. Am. Chem. SOC., 74, 4940 (1952). 27. Taft, R. W., M. S. Newman, and F. H. Verhoek,J. A m . Chem. SOC.,72, 451 1 (1950). 28. Tirouflet, J., Bull. Soc. Sci Bretagne Spec., 26,89 (1951); CA, 47,8694 (1953). 29. Kindler, K., Ann., 452, 90 (1927);Ber.. 69B, 2792 (1936). 30. Berliner, E., and H. Altschal,J. A m . Chem. SOC.,74, 41 10 (1952). 31. Smith, G. G., D. A. K. Jones, and D. F. Brown, J. Org.Chem., 28,403 (1963). 32. Bordwell, F. G., G. D. Cooper, and H. Moirta,J. Am. Chem. SOC., 79, 376 (1957). 33. Bright, R. D., and C. R. Hauser,J. A m . Chem. SOC.,61, 618 (1939). 34. (a) Hartman, R. J., and A. M. Borders, J. Am. Chem. SOC.,59, 2107 (1937); (b) Hartman, R. J., and A. B. Gassman,J. Am. Chem. SOC.,62, 1559 (1940). 35. (a) Roberts, J. D., et al., J. Am. Chem. SOC.,73, 2181 (1951); 72, 628 (1956); 71, 2923 (1949); 72, 408 (1950); (b) Benkeser, R. A., ef al., J. Am. Chem. Soc., 78, 682 (1956); (c) Chapman, N. B.,J. Chem. SOC.,1824 (1962). 36. Ritter, J. D. S., and S. I. Miller, J. A m . Chem. SOC.,86, 1507 (1964). 37. Pews, R. G., Y. Tsuno, and R. W. Taft, J. A m . Chem. SOC.,89, 2391 (1967). 38. Bkguin, C., Bull. SOC.Chim.fiance, 4214 (1967). 39. Eaton, D. A,, and W. A. Sheppard, J. Am. Chem. SOC.,85, 1310 (1 963). 40. Dewar, M. J. S., and A. P. Marchand,J. Am. Chem. SOC.,88, 3318 (1966). 41. Unpublished results of R. G. Pews, P. Heffley, and R. W. Taft.

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TABLE 1V

IEZ' P60' ZEP' 28 I' 6PI' P I I' 9s I' ILLE9" LE 1LEI' ZSI' ESI'

89 I' ESZ' 69 I' PZZ' 190' ZLI' SE I'

s 10.

e801' PLO' eLZI' eE I I' 6P0 eP80' 9960' eL 10'

0

*

r

c

.I72 .138 .I54 .207 .072

.20 .74 .33 .33 .14

.064 .157

.059 .065 .070 .I10 .035

.07 .35 .I5 .18 .07

37 38 39 40 41

.I69

.030

55 1.56 .73 .56 .29

.144 .146 .245 .239

.474 .290 .339 .329 .143

F-nmr Shifts

.358 .I56 .288 .393 .I72 .384 .230 .241 .204 .292 .257

Other Rates

.32 .I9 .28 .22 .24 .04 .24 .24 .06 .I2 .04

.20 .I5

.05

.03

.15 .69 .32 .25 .17

.05 .05

.05

.05

.lo5 .07 .I 3 .05 .11 .03 .07

.06 .05 .I0 .08

.I21 .I29 .I52 .I53 .086

.157 .056 .I46 .097 .076 .269 .062 .048 .I80 .I21 .289

.274 .I54 .I23 .124

.12 .36 .09 .27 .I3

.06 .04 .01

.09 .05

.I1 .04 .08 .06 .04 .03

.05 .02 .05 .04

.064

.170

.I 24a .066 .043

.120 .037 .088 .111 .031 .296 .081 .047 .202 .099 .058

.221 .066 .056 .061

.I4 2.49 .48 .28 .35

.05

.09 .09 .23 .04

.05

.ll .07 .I2 .06 .05

.05

.05

.05 .05

.I21 .462 .225 .I76 .173

.I 17 .059 .I34 .111 .037 .564 .088 .087 347 .097 .316

.225 .147 .057 .085

*

Datum for NMe, not included, no R value listed. bData for NMe,, SCF, and SOCF, not included, no R values listed. Results including datum for NMe, and corrected datum for NHCOMe, which were not available at time UR(BA) values of Table I were defined. Results including data for NMe,, NHCOMe and CO,R, which were not available at time UR(BA) values of Table I were defined.

a

.195 .069 .I74 .237 .070 .334 .I18 .110 .194 .I77 .080

.17 .08 .I6 .I3 .I0 .03 .I3 .ll .05 .07 .01

.072 .013 .065 .076 .021 .274

.06 .02 .06 .04 .03 .03 .06 .03 .05 .03 .03

26 27 28 29 30 31 32 33 34 35 36

.055

.168 .069 .I10 .I14

.04 .02 .09 .07

.258 .058 .059 .041

.05 .02 .05 .03

22 23 24 25

12

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

Table IV lists comparative SD and f values for fittings of all of the reactions of Table 11 and 111 with each of the UR scales derived in this paper. The comparison includes figures for fittings with F and R valu,es of Swain and Lupton (S & L) and fitting with the Hammett equation. We believe the results given in Table IV provide a clear confirmation of the uniqueness and limited generality of the UR(BA) scale. Very consistently, the fit achieved by the UR (BA) scale is shown in Table IV to be superior by significant factors to that achieved by any of the other scales or by the simple up treatment. This fact is clearly reflected in the overall f values and the similarly weighted root-mean-square f values, F 3 dlCnifiZ/N, sum taken over all reactions. The value of F is .067 for the basis sets of Table I1 (compare with overall f of .058). The comparable F values are .140 for u i , .088 for S & L, and .155 for I?(,,) with the data differences as explained in Table IV. For all sets of Table IV, the corresponding , .097 for S & L, and .209 for a@). figures are .073 for uR(BA), .143 for The OR values of Table I show notable similarities to the previously proposed values. The small differences, of course, result from the influence of the seven other reactions, besides reaction 1, which were used to define the results in Table 1. Three substituents may be singled out as having appreciably modified values: namely, SMe, OC6H5, and NHCOMe. These three substituents give deviations twice as large as for any other substituents in the fitting of reaction 1 and are largely responsible for the substantially greater fvalue for this reaction than for the other seven basis sets. Either experimental errors or specific hydration effects are probably involved with these substituents in reaction 1. For example, the larger -UR value for OC6HS than OCH3 derived from log ( K / K o ) values for reaction 1 is unreasonable (and not observed in any other reaction series). The UR value of -.55 for OC6Hs-defined by the data of reaction 8 is probably a more reasonable value than the -.58 value based upon the data of both reactions 1 and 8. Swain and Lupton neglected without comment the above point regarding the OC6H5 substituent (giving -R for OC6H5 > -R for OMe). Much more serious in its consequences is the fact that Swain and Lupton, again without comment, have neglected the available reliable data for the NMez substituent. Because the NMez substituent is a highly important one with regard to data sets covering a full range of CJR electronic effects, the fittings achieved by neglect of this substituent should be taken less seriously (even though statistically we have attempted to account for the omission in the fvalues through the RMS values). A brief discussion of the systematics of solvent effects on the pi, p~ , and h values of Tables I1 and I11 is presented in the discussion section. However, it is worthy of note here that sets 7, 37, 38, 39, 40, and 41, which involve nonhydroxylic solvents, are fitted with comparable precision to that for reaction series in aqueous or mixed aqueous organic solvents. The present analysis does not support the previous assignment (7b) of ion-pair formation of benzoic acids

I?;

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

13

with 1,3-diphenylguanidine (DPG) in benzene (reaction 7) as a sigma zero type, but instead supports assignment as a BA type (with relatively small Xp = .69) in accord with structural considerations.

B. ur; (A type) Values The ionization of anilinium ion in water at 25" was adopted as the basis set for this type. This choice was dictated by the fact that extensive reliable data for both m- and p-substituents are available which meet the minimal substituent requirement in both series. Two methods were found which give essentially the same set of ur; parameters. First, the UR(BA) parameters for the substituents CH3, F, C1, and Br were assumed to apply to the data for m-and p-substituted anilinium ions. This constraint was sufficient to give a or; set essentially equivalent to the values given in Table V. Second, the data include results for the TABLE V Pi Delocalization Parameters Substituent - -

U B

uR(BA)

OR(A)

-.83 -.82 -.36 -.61 -.58 -.32

-.34 -.48 -.45 -.I4 -.I I .04 -.45 -.23 -.I9 -.I1

Uii

~

-N(CH,)a -NH, -NHCOCH, -OCH, -OC,Hs -SCH, -CH, -C& -F -c1 -Br -I -H -SOCH, -SCF, -Si(CH,), -SF, -SOCF, -CF , -SO,CH, -CN -COaR -NO, -COCH,

(.06)a -.52 (.12) -.48 (.26) -.25 (.27) -.45 (.38) -.34 (.23) -.20 (-.04) -.I1 (.lo) -.11 ( S O ) -.34 (.46) -.23 (.44) -.19 (.39) -.I6

(.OO) (50) (.42) (-.lo) (57) (.64) (.45) (S9) (-56) (.30) (.65) (.28)

.oo .oo

.04 .06 .06 .08 .08 .I2 .I3 .14 .I5 .16

a U I values are given in parentheses. b cf. discussion.

-.11 -.I 1

-.45 -.23 -.19 -.16

.oo .oo .04 .06 .06 .08 .08 .12 .I 3 .14 .I5 .16

.oo

.I4 .14 .20 .17 .38 .33 .34 .46 .4 7

-1.75 -1.61 -.86 -1.02 -.87 b

-.25 -.30 -.57 -.36 -.30 -.25

.oo .oo .04 .06

.06 .08 .08 .12 .I 3 .14 .15

.16

14

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

m-and P - N ( C F ~ )substituent ~ (9). This substituent by the very sensitive F-nmr shift method (10) is found to have OR = .OO 5 .01. Consequently, in the anilinium ion ionization equilibria, it is a useful and presumably valid assumption to take R Z.00 for m- and p-N(CF3)*. This assumption gives log (KP/Ko)/log ( K m l K o ) = P I P = pp/$ = 1.46/1.31 = 1 .I 1. Because p y is obtained as 2.9 . I (this value is essentially independent of the OR scale used in eq. (1): see subsequent discussion of meta reaction types), we have pf = 3.2 k .l. The generation of the u i (A) basis set is then completed (using the p-substituent data only) by the assignment of p$ = 3.50, which gives a 0% value of -.11 for the CH3 substituent. Because both methods give essentially equivalent results, the results given in Table V were adopted. Interestingly, slightly better precision of fit of the u ~ ( A )scale is achieved if the identity of uR(BA) and aEcA)scales is not extended to the I substituent (i.e., for I , o ~ ; ( A )= -.11 and UR(BA) = -.16). For all other substituents, ugcA, and uR(BA) values differ very significantly (Table V) as do the statistics of fitting of data for various reaction types b y use of these two scales (Tables IV, VII, IX, XII, XIV). Table VI lists values of &, pg , Ap, n, SD, andfobtained for twenty-four reaction series and one proton nmr set of the a i type, each of which contain data for sufficient numbers (n) and kinds of para substituents to provide a reasonably critical analysis. Also given in Table VI is the p value obtained with the single substituent parameter a@)., as listed by Ritchie and Sager (2m). It is immediately apparent from the reaction descriptions that the C J ~ ; (scale ~ ) applies to rate and equilibrium ionization of a proton from the functional groups -CH3, - N G , -N(CH3),Ht, -NH2, -SH,-OH, etc. There is, however, the important restriction (as discussed fully subsequently) that the ionization of p-substituted phenols in certain hydroxylic solvents may not be included. In Table VII are shown the comparative SD and f values for fittings of these reactions with the various substituent parameter scales. These results, we believe, provide a dramatic confirmation of the uniqueness and “limited” generality of the scale. In all but three of the twenty-five sets, there is significantly better fitting by eq. (1) with values than by the single substituent parameter treatment, pa@). In contrast, the single substituent parameter treatment gives fits better by significant factors than the Swain treatment (in spite of the additional substituent parameter in the latter) in 50% of the sets of Table VII. In only four cases does the Swain treatment give better fit than P O ( , ) by significant factors, and in three of these the absence of an R value for the NMe, substituent precludes complete coverage of the data by the Swain parameters. The F value is .194 for pa@, and .212 for the R and F treatment. In n o case does the Swain treatment give better fit than eq. (1) with ~ j i ( ~values ) (F = .080). In fact, in many sets, the SD and fvalues in the Swain treatment (also with UR(BA) and a;) are so large that the fittings are meaningless. In spite of this poor quality of fit, the applicability of the R and f +_

VI

c

20.

19.

18.

8. 9. 10. *11. 12. 13. 14. 15. 16. 17.

1. 2. 3. 4. 5. 6. 7.

No.

Aminolysis, ArNH, with HCO,H, aq. pyridine 100" Substitution, ArNH, with 2,4-diNO,C6H,Cl, EtOH, 100" T-H Exchange, ArCH, + RNHLi

4.502

-2.516

-2.624 3.764

-1.862

Rates

6.545 3.439 1.958 2.1 10 2.407 2.494 5.084 5.875 4.989 12.159

3.476 3.486 3.890 4.5 94 3.962 4.075 4.5 38

P%

-1.562

5.697 3.485 1.816 2.628 2.971 3.187 5.499 6.575 5.085 9.306

3.088 3.204 4.198 4.708 3.944 3.753 4.506

Ionization, ArNH:, H,O, 25" Ionization, ArNH:, 50% aq. EtOH, 25" Ionization, ArNH:, MeOH, 25" Ionization, ArNHi, EtOH, 25" Ionization, ArNMe,H+, H,O, 20" Ionization, ArNMe,H+, H,O, 25" Ionization, ArNMe,H*, 45% dioxane -H,O, 25" Ionization, ArNH,, NH,(l) Ionization, ArNH,C,H:, 20% aq. EtOH Ionization, ArNHSO,C,H,, H,O, 20" Ionization, ArSH, 48% aq. EtOH, 25" Ionization, ArSH, 95% aq. EtOH, 22" Ionization, ArOH, 95% aq. EtOH, 22" Ionization, ArOH, acetone Ionization, 2,6-diMe phenol, acetone Ionization, ArNHC,H,, DMSO, 25" Oxidation, [Ar(C,H,)C,H,F@)] -,DMSO, 25"

Equilibria

P4

Reaction

1.20

.96

1.19

1.15 .99 1.08 .80 .81 .78 .92 .89 .98 1.31

1.13 1.09 .93 .98 1.oo 1.09 1.01

xp

.14

7

.08 .07

4

.04 6

5

5

6 10 7 8 10 7 6

5

.12 .06 .03 .08 .10 .10 .28 .36 .7 1 .44

.10

5

4

.03 .03 .04 .09 .14

SD

18 6 4 4 6

n

Anilinium Ion Type Series. Fits t o Eq. (1) with Use of C T ~ ( AValues )

TABLE VI

'

,056

.084

.049

.043 .026 .030 .058 .069 .063 .093 .092 .217 .078

.018 .015 .034 .072 .039 .05 8

.015

f

3.1 11

-2.208

-1.50,3

5.835 3.127 1.576 1.966 2.428 2.581 4.870 5.700 4.313 7.953

2.862 3.006 3.673 4.195 2.864 3.593 3.917

P

m

-

H,)C, H, %)I-,

DMSO,25" -10.37

-13.11

.776

6.436

6.103

5.031

-22.80

' nmr Shifts

1.579

-12.80

F-nmr Shifts

N'

1.45 3

pg

.879

H-nmr Shift _____

.932

5.572

5.648

5.855

,499

PP

1.23

1.74

1.09

.83

1.16

1.08

.86

1.76

kP

7

7

15

6

6

6

12

5

n

.36

.71

.I1

.01

.25

.19

.I5

.03

SD

.063

.090

.I33

.030

.072

.065

.054

.077

f

-8.54

-15.04

1.280

.752

5.322

4.905

4.792

.605

P

1. (a) Bigs, A. I., and R. A. Robinson, J. Chem. SOC.,388 (1961); (b) Bordwell, F. G., and P. J. Boutan,J. Am. Chem. Soc., 78, 87, 854 (1956); 79, 717 (1957); (c) Bordwell, F.G., and G. D. Cooper, J. Am. Chem. SOC., 74, 1058 (1952); (d) Benkeser, R . A . , and H. R. Krysick, J. Am. Chem. SOC., 75, 2421 (1953); (e) Vandenbelt, J., C. Henrick, and S. Vandenberg, Anal. Chem., 25, 726 (1954); ( f ) Robinson, R. A., and A. 1. Biggs, Aust. J. Chem., 10. 128 (1957); (g) Willi, A. V., and W. Meier,HeZv. Chim. Act., 39, 318 (1956); (h) Fickling, M. M., A. Fischer, B. R. Mann, J. Packer, and J. Vaughan, J. Am. Chem. Soc., 81, 4226 (1959); (i) Fawcett, F. S., and W. A. Sheppard, J. Am. Chem. SOC.,87, 4341 (1955); 0 ) Sheppard, W. A., J. Am. Chem. SOC.,84, 3072 (1962); 85, 1314 (1963); (k) Kuhn, R., and A. Wassermann,HeZv. Chim. Act., 11, 3 (1928); (I) Kieffer, F., and P. Rumpf, Compt. Rend., 238, 360 (1954); (m) Sager, E. E., e l aZ., J. Rex NatZ. Bur. Stand., 35, 521 (1945).

28.

[ ArC(C,

ArNH, , DMSO, 25"

a

27.

25.

24.

23.

ArOH, DMSO, 25"

ArOH + H,SO,,

*26.

-.+

Substitution, C1- Q -X with SC,H;, MeOH, 35" NO* Substitution, F-X with OC,H;, EtOH, 49.6" Cleavage of ArCH,SiMe,, OH-, 39% aq. MeOH, 49.7" Deprotonation, ArCH(NO,)CH, with O H - , H,O, 25"

NO*

Hydrolysis, ArOS0,H H,O, 49"

Reaction

*22.

21.

No.

TABLE VI (continued)

c. 4

2. Baddeley, G., J. Chadwick, and H. T. Taylor,J. Chem. SOC.,2405 (1954). 3. Kilpatrick, M., and C. A. Arenberg, J. Am. Chem. Soc., 75, 3812 (1953). 4. Reference for set no. 3. 5. Willi, A. V.,Helv. Chim. Act., 40, 2019 (1957). 6. Fickling, M. M., A. Fischer, B. R. Mann, J. Packer, and J. Vaughan,J. Am. Chem. Soc., 81, 4226 (1959). 7. Sheppard, W. A., J. Am. Chem. Soc., 87, 2410 (1965). 8. Birchall, T., and W. L. Jolly, J. Am. Chem. Soc., 88, 5439 (1966). 9. Dolman, D., and R. Stewart, Can. J. Chem., 45,903 (1967). 10. Willi, A. V., Helv. Chim. Act., 3 9 , 4 6 (1956). 11. (a) Schwarzenbach, G., and H. A. Egli, Helv. Chim. A c t , 17, 1176 (1934); (b) Schwarzenbach, G., and E. Rudin,Helv. Chim. Act., 22, 360 (1939); (c) Bordwell, F. G., and H. M. Andersen, J. Am. Chem. Soc., 75, 6019 (1953); (d) Bordwell, F. G., and P. J. Boutan,J. Am. Chem. SOC.,78, 856 (1956). 12. Reference (b) for set no. 10. 13. (a) Schwarzenbach, G., and H.Egli,Helv. Chim. Act., 17, 1 176, 1183 (1934); (b) Reference (b) for set no. 10. 14. Fischer, A., G. J. Leary, R. D. Topsom, and J. Vaughan,J. Chem. Soc., (B), 846 (1967). 15. Reference for set no. 13. 16. Dolman, D., and R. Stewart, Can. J. Chem., 45, 9 I I ( I 967). 17. McKeever, L. D., and R. W. Taft, J. Am. Chem. SOC.,88, 4544 (1966). 18. Davis, 0. C. M., and F. W. Rixon,J. Chem. SOC.,107, 728 (1915). 19. Van Opstall, H. J.,Rec. Dm.Chim., 52, 901 (1933). 20. Streitwieser, A., Jr., and H. F. Koch, J. Am. Chem. Soc., 86, 404 (1964). 21. Burkhardt, G. N., C. Horeux, and D. I. Jenkins,J. Chem. Soc., 1649 (1936). 22. Porto, A. M., L. Altieri, A. J. Castro, and J. A. Brieax,J. Chem. Soc., (B), 963 (1966). 23. Bevan, J.,Bull. Chim. SOC.Fr.,1551 (1959). 24. Eaborn, C., and S. H. Parker, J. Chem. SOC., 126 (1955); Bott, R. W., C. Eaborn, and B. M. Rushton,J. Orgunometallic Chem., 3, 448 (1965). 25. Bordwell, F. G., and W. J. Boyle, Jr.,J. Am. Chern. Soc., in press. 26. Tribble, M. T., and J. G. Traynham,J. Am. Chem. SOC.,91, 379 (1969). 27. Axenrod, T., P. S. Pregosin, M. J. Wieder, E. D. Becker, R. D. Bradley, and G. W. A. Milne, J. Am Chem. Soc., 93,6536 (1971). 28. Dayal, S. K., S. Ehrenson, and R. W. Taft, J. Am. Chem. SOC.,94,9113 (1972).

m

c

.lo

9.

8.

11.

12.

.I4 .12 .06 .03 .OX .10

6. 7.

5.

.015 .018

.03 .03 .04 .09 .I4

1.c 2. 3. 4.

.043 .026 .030 .058 .069

.058

.015 .034 .072 .039

f

OR(A)

SD

10.

No.

.40 .38 .17 .34 .28 .36 .25

.75

.44 .16 .18 .30

SD

f

.060 .144 .252 .251 .167

.155

.380 .I57

.111

.078

.I00

.244

OR(BA)

.I8

.15 .26

.58 .30 .29 .34 .23

.31 .16 .22 .27

SD

4

.123 .097 .141 .184 .122

.117

.092 .lo0 .293 .117

.lo0

.I74

f' .28 .38 .49 .88 .47 .47 .53 .42 .35 .44 .32

.60

SD

4 .323 .172 .I64 .183 .446 .186 .I93 .193 .I78 .319 .310 .218

f'

SD/RMS for Para A Series

TABLE VII

Values of SD andf

.18 .I6

.44 .34 .38 .29 .30 .25

.42 .22 .24 .36

SD

f

.128 .231 .123b .lo7

.lo5

.239a .I38 .lo2 .I33 .210b .135 .I59

S&L

.24 .I I .I 3 .09 .74 .09 .21 .29 .13 .I4 .42 .30

SD

f

.033 .375 .036 .086 .106 .056 .128 ,293 .202

.056

.i33 .107

06)

.71 .36

.ll

.10 .28 .36 .71 .44 .04 .08 .07 .03 .15 .19 .25 .01

.063 .093 .092 .217 .078 .049 .084 .056 .077 .054 .065 .072 .030 .133 .070 .063

.32 .52 .70 .96 2.12 .17 .43 .24 .09 .65 1.03 .60 .07 .19 2.74 1.97

.I98 .173 .178 .294 .373 .195 ,463 .191 .215 .228 .349 .174 .143 .240 .335 .344 .62 .60 .06 .15 2.02 1.50

.51

.24 .46 .62 .81 1.70 .ll .48 .22 .07

I

a Data for SCF, and SF, not included, no R value listed. Datum for NMe, not included, no R value listed. Basis set

13. 14. 15. 16. 17. 18. 19. 20. 21. *22. 23. 24. 25. 26. 27. '28.

.150 .151 .158 .249 .299 .123 .513 .I77 .163 .I79 .210 .I74 .121 .186 .254 .262 .43 .12 .88 1.32 .87 .10 .26 3.55 2.60

.54

.40 .77 .97 1.08 2.85 .22

.250 .256 .247 .329 SO2 .252 .579 .342 .280 .308 .444 .253 .214 .322 .446 .456 .06 .19 2.43 1.26

.55

.96 .9 8 .16 .31 .I 8 .07 .62 1.oo

.55

.22 .44 .139 .146 .139 .294 .1 60b .175 .329 .143 .155 .216 .337 .160 .I19 .234b .306 .213b

.32 .40 .46 .84 1.68 .04 .23 .19 .07 .65 56 .34 .06 .19 2.38 1.44

.loo

.135 .239 .299 .252

.199 ,133 .117 .256 .296 ,048 .247 .152 .170 .226 .190

20

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

parameters to reactions such as those of Table VI was clearly implied by Swain. The explanation lies in the fact that not a single reaction from Table V1 was considered, nor was any consideration given t o the omission. Swain included the ionization of phenols in water at 25" as the only 06, example, and we have found (as noted above and discussed subsequently) this single set to be notably exceptional. In Table V, the u i ( * ) value given for the p-NMe2 substituent is a secondary value derived from the fittings from among the other reactions of Table VI. The neglect of the NMe, substituent in Swain's treatment was critical in view of the large and variable UR values for this substituent shown in Table V.

C. ;a Values Series for which neither tR nor -R substituent effects from the para position are enhanced or retarded by quinoidal resonance effects have been proposed (2e, 7b) as constituting a unique class. Reactions in which a methylene group is interposed between the side-chain reaction center and the benzene ring were considered especially appropriate for this sigma zero (SO) class (7b). However, data of this type were meager, and substituents effects in such reaction series are relatively small compared to small specific solvent effects or to experimental errors. The F-nmr shielding effects of p-substituents in fluorobenzenes clearly do not suffer from the latter disadvantage, and these substituent effects appeared to be well correlated by ;0 values obtained from the available reaction series data (7b). Consequently, the F-nmr shifts were given a strong weighting in defining the originally proposed ug scale. A number of apparently appropriate reaction series data have become available in recent years. Using essentially the above structural considerations, we have found 14 reaction series which we believe are appropriate for the SO classification. These reactions are listed in Table VIII. Unfortunately, only reaction 1 meets the minimal substituent requirements for a basis set. The other reactions contain sufficient numbers and kinds of substituents to be considered only partially adequate. In view of this shortcoming and the problems which arise from the relatively small R effect contribution to sigma zero substituent effects, the following procedure was adopted. The F-nmr shielding effects for three sets were added to the fourteen sets of reaction data: the p-FC6H4X, cyclohexane; p-FC6H4X, methanol; p-FC6H40C6H4X,benzene. It should be noted here that the units of the F-nmr shifts compared to the log (k/k,) values are such that sets 15, 16 and 17 are very highly weighted in the determination of the u$ scale. In the statistical sense, this weighting is justified by the relatively high precision of the F-nmr shifts. In the physical sense, however, it is not clear that the high weighting is justified. Although F is the weakest pi electron donor of the united-atom-like first-row pair donor

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

21

substituents, it has a definitely finite UR value in any of the scales of Table V. Consequently, enhanced or retarded effects on the F-nmr shifts associated with para quinoidal type pi delocalization of the fluorine atom probe may be expected to contribute to some extent (1 1). In the absence of data which are truly ideal in the physical sense, the fluorobenzene and fluorodiphenyl ether shifts have been utilized as described below. The comparable precision of fit found upon putting the F-nmr shifts and reactivity sets together in the generating of the u i scale provides some support for this procedure. The u i values presented in Table V were obtained from best fitting the seventeen adopted basis sets as follows: first, the 01 values of Table I and the UR(BA) values of TableV for NOz, C1, Br, and I were used. For these substituents, values and the original u i values did not differ significafitly. The set of u$ values so generated was compared with the u R ( ~ and ~ ) ui(A) sets. If differences of a few hundredths of a unit existed, it was assumed and subsequently verified that adjustment to a common value could be accommodated with no significant loss of precision of fitting. In this manner, for example, the values of uR(BA) and ;u for all +R substituents could be set equal. The first generated ug value for the CH3 substituent was -.16. However, this value is considered to be an artifact of the F-nmr shielding data for p-FC6H4X. All of the data for this substituent is satisfactorily fitted by the value of -.I1 given in Table V. Table VIII lists values of p f , p g , hp, n, SD,f; and Hamrnett p obtained for the seventeen sigma zero type basis sets with the u i values of Table V. Also listed are these results for 10 additional data sets. The comparative values of SD and f obtained with the various substituent parameters are given in Table IX. At first glance, it appears that the 14 basis set reaction series do not discriminate nearly as well between the various scales of OR as did the data of the previous sections. Seven of the fourteen sets are best fitted by a$ ; four sets are best fitted by Swain and Lupton parameters; two sets are best fitted by u ~ ( A ) parameters, and one set best fitted by UR(BA). A more complete examination reveals that in only three of the reactions (nos. 2, 9 , 13) not best fitted by the ug scale is the fitting by the competing scale better by a significant factor of two to three. Further, for all 14 sets, fits with cr; fall within the range o f f values of .022 to .126, with an overall value of .096. (The root-mean-square value, F, is .091.) Other parameters give overall fits which are notably poorer. For example, the root-mean-square F values for all 27 sets of Table VIII are us, .095;0R(,A), .159;S & L, . 1 8 8 ; ~ j j ( ~ .251;and ), u;, .257. The three F-nmr shielding sets (nos. 15, 16, 17) are fitted with uniquely better precision by the u i scale. The SD for each of these sets is smaller by factors of two to three times than that achieved with any other parameters (Table VIII). This result is consistent with the fact that these sets have much larger h values (1.5 t o 4.2) than do the reaction series (.7 to 1.0) and

2

*15. *16. 17.

F-nmr Shift, ArF, MeOH, 25" F-nmr Shift, ArF, cyclohexane, 25" F-nmr Shift, ArOC,H,F(,), benzene, 25"

Saponification, ArCH,O,CMe, 60% aq. acetone, 25" Saponification, ArCH,CO,Et, 60% aq. acetone, 25" Saponification, ArCH,CO,Et, 88%aq. EtOH, 30" Saponification, ArCH,CO,Et, 60% aq. acetone, 25" Saponification, Ar(CH,),CO,Et, 88% aq. EtOH, 30" Saponification, I-Ar-cyclopropyl CO,Et, aq. Decomposition, (ArO),CO(,), 363"

8. 9. 10 11. 12. 13. 14.

6. 7.

5.

Ionization, ArCH,CO,H, 50% aq. EtOH, 25" Ionization, ArCH,CO,H, 10% aq. EtOH. 25' Ionization, ArCH,CO,H, H,O, 25" Ionization, ArCH,NH:, 50% aq. EtOH, 25" Ionization, ArCH,NH:, H 2 0 , 25" Ionization, ArPO,(OH)-, H,O, 25" Ionization, f-Arcyclopropyl CO,H, 50% aq. EtOH, 25"

Reaction

*l. 2. 3. 4.

No.

-9.021 -7.033 -3.210

F-nmr Shifts

.7 14 1.066 1.173 1.044 .641 .857 ,182

Rates

.755 .556 ,484 1.282 1.082 1.082 S72

Equilibria

A. Basis sets

-31.17 -30.58 -4.854

.775 .159

.520

.718 .795 .790 .869

.646 .470 ,433 1.269 1.057 1.142 .501

BR

3.46 4.35 1.51

1.01 .75 .67 .83 .81 .90 .87

.86 .85 .90 .99 .98 1.06 .88

hP

Sigma Zero Sets. Fits to Eq. (1) with Use of &Values

TABLE VIII

5

22

21

7

5

8 7

5

8 7

11 9 7 8 8 7 5

n

.56 .56 .05

.03 .04 -05 .02 .02 .02 .01

.02 .02 .01 .05 .05 .04 <.01

SD

.072 .076 ,027

.086 .095 ,121 .063 .lo4 ,049 ,126

.060 ,087 .067 ,114 .119 ,099 .022

f

-14.99 -1 3.30 - 3.446

,732 ,985 .813 .981 .404 .835 .142

.562 .555 .481 1.097 .908 .937 ,553

P

E

Methanolysis 4-X, 2,6-diNOZchlorobenzene, MeOin MeOH, 0" Piperidine with 4-X, 2-NO, chlorobenzene, benzene, 45" Acetolysis. 6-X-syn-9-Arnorbornenol brosylates, HOAc, 77.6"

-1.851

5.369

5.96 1

-1.530

7.069

8.242

.83

1.32

1.38

4

11

7

.03

.25

.19

-1.73

5.436

.loo .033

5.545

.094

1. Wepster, B. M., private communication. 2. Reference for set no. 1. 3. (a) Dippy, F. J., el al., J. Chem. Soc., 161, 1888 (1934); 343 (1935); 644 (1936); 355, 1774 (1937); (b) Fischer, A., B. R. Mann, and J. Vaughan,J. Chern. Soc.,1093 (1961). 4. Reference for set no. I . 5. Reference for set no. 1. 6. Jaffb, H. H., et al., J. Am. Chem. SOC.,75, 2209 (1953). 7. Fuchs, R., C. A. Kaplan, J. J. Bloomfield, and L. F. Hatch, J. Org. Chem., 27, 733 (1962). 8. Tommila, E . , A n n Acad. Sci. Fennicue, 59A, 3 (1942). 9. Norman, R. 0. C., et al., J. Chem. SOC.,3247 (1961). 10. Kindler, K.,Ann., 452, 90 (1927). 1I . Yukawa, Y., Y. Tsuno, and M. Sawada,Bull. Chem. SOC.Japan, 39,2274 (1966). 12. Fuchs, R., and J. J. Bloomfield,J. Org. Chem., 28, 910 (1963); Fuchs, R., and J. A. Caputo,J. Org. Chem., 31, 1524 (1966). 13. Fuchs, R., and J. J. Bloomfield,J. Am. Chem. Soc., 81, 3158 (1959);J. Org. Chem., 28,910 (1963). 14. Smith, G. G., D. A. K. Jones, and R. Taylor,J. Org. Chem., 28, 3547 (1963). 15. Taft, R. W.,etal., J. Am. Chem. Soc., 85, 3146 (1963). 16. Reference for set no. 15. 17. Unpublished data of R. G. Pews and R. W. Taft. 18. Miller, J.,Aust. J. Chem., 9, 61 (1956). 19. Greizerstein, W., R. A. Bonelli, and J. A. Brieux, J. Am. Chem. Soc., 84, 1030 (1962). 20. Tanida, H., Y. Hata, S. Ikegami, and H. Ishitoba, J. Am. Chem. Soc., 89, 2928 (1967).

20.

*19.

18.

Rates

B. Other sets

N

-9.035 -1.676 -1.31 I -5.47 -1.33

nmr Shifts

4.2 10.1

pfl

-29.45 -1.537 -1.175 -21.19 -21.20

-133.2 -170.4

ir Intensities -~

4

3.26 .92 .90 3.87 15.9

-31.7 -16.8

hP

6

7 7 6 11

20 9

n

.6 .9

.29 .07 .03

4.7 4.6

SD

.044 .I06 .079 ,096 ,133

.140 ,128

f

-13.00 -1.426 -.goo -10.89 -9.66

-41.76 -38.10

P

Ray, G. J., R. J. Kurland, and A. K. Colter, Tetrahedron, 27, 735 (1971).

Brownlee, R. T. C., A. R. Katritzky, and R. D. Topsom,J. Am. Chem. SOC.,87, 3261 (1965). Katritzky, A. R.,R. F. Pinzelli, M.V. Sinnott, and R. D. Topsom,J. Am. Chem. SOC.,in press. Illuminati, G., R. W. Taft, unpublished data. Dayal, S., S. Ehrenson, and R. W. Taft,J. Am. Chem. Soc., 94,9113 (1972). Reference for set no. 24. (a) Maciel, G. E., and J. J. Natherstad,J. Chem. Phys., 42, 2427 (1965); (b) Khami, K. S., and J. B. Stothers, Can. J. Chem., 45, 233

F-nmr Shift, 4-X, 3,5-diMefluorobenzene, cyclohexane F-nmr shift, 4'-X, 4-F diphenylmethanols, CH, C1, F-nmr Shift, 4'-X 4-F diphenylmethanes, CH,CI, C-13 nmr Shift, XC,H, (para position) C-13 nmr Shift, Ar,COH (para position), THF.

23. *24. 25. *26. 27.

21. 22. 23. 24. 25. 26. (1967). 27.

(A-100)'/2 1600 cm-' band, X-C,H, (A-80)'/*, 1640 cm-' band, XCH=CH,

Reaction

*21. 22.

No.

B. Other sets

TABLE VIII (continued)

VI

h)

a

.02 .02 .02 .o 1 .56 .62 .05 .19 .25 .03 4.7 4.6 .29 .05 .03 .58 .9

.05

<.01 .03 .04

.04

.02 .02 .01 .05 .05

SD

0 i

f

.033 .140 .128 .044 .072 .017 .096 .133

.loo

.060 ,087 .067 .114 .I19 .099 .022 .086 .095 .121 .063 ,104 .049 .I26 .072 .083 .027 .094 .04 .02 .03 .04 .03 .04 .04 .01 .01 1.49 1.29 .15 .35 .36 .04 7.7 8.6 1.60 .07 .06 .81 1 .o

.08

.04 .03 .02 .05

SD

OR

f

.115 .203 .lo5 .084 .lo2 ,096 .075 .096 ,165 .035 .153 .193 .174 ,081 .176 .146 .048 .228 .235 .243 .091 .146 .134 .138

.131 .125 .lo5

(BA)

.05 .01 .01 .09 .04 .10 .02 .04 .05 .08 .04 .04 .05 .01 2.83 3.00 .30 51 .35 .08 12.4 9.2 1.52 .19 .08 2.61 332

SD

0R(A)

datum for NMe, not included, no R value listed. data for NMe, and SF, not included, no R values listed.

*l. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. *15. *16. 17. 18. *19. 20. '21. 22. 23. * 24. 25. *26. 27.

No.

TABLE IX

f SD

f SD

~~

~

.220 .04 .226 .02 .173 .01 .222 .06 .303 .08 .170 .06 .123 .01 .118 .02 ,158 .02 .05 .122 .170 .02 .262 .03 .076 .01 .250 .01 .323 2.03 .289 1.98 ,144 .19 .291 .35 .227 .34 .089 .02 .348 10.2 .347 10.1 .366 1.23 .208 .05 ,268 .01 .262 .86 .211 .7

S&L

f .152a .082 .079 .134 .201 ,140 ,052 .079 .041 .lo2 .044 .123a .020 .179 .282b .285' .I02 .179 .137 .031 .315d .279 .187 .063a .030a .169a .127a

.ll .05 .04 .13 .13 .09 .04 .04 .I2 .20 .09 .ll .05 .02 3.99 4.30 .19 .39 .34 .16 29.3 35.8 4.3 .21 .16 3.19 5.10

SD

f .395 .226 .234 .289 .339 .211 .179 .134 ,295 .452 .242 .468 .151 ,380 .502 .557 .102 .196 .139 .200 .824 .938 .649 .287 .375 .529 .731

data for NMe,, SCF,, SF, and SOCF, not included, no R value listed. data for NMe,, SF, and SCF, not included, no R values listed.

.181 .06 .031 .05 .072 .03 .199 .10 .093 .12 ,217 .07 .090 .03 .149 .03 ,112 .06 .177 .05 .116 .06 .188 .06 .146 .03 .186 .02 .355 2.53 .395 2.18 ,163 .27 .259 .57 .141 .56 .097 .07 .379 11.7 .252 12.4 .231 2.41 .15 .252 .196 .ll .433 1.58 .455 1.5

0;

Values of SD and f for 0; Sets

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

26

consequently are much more discriminating between the resonance effect scales. However, for the reasons noted above, further evidence for the uniqueness of the u$ scale (in reaction rates and equilibria, in particular) is desirable. Accordingly, additional reactivities and physical property sets have been sought and analyzed to provide more critical evidence in support of the uniqueness of the u$ on a "limited generality" basis. The reactivity sets include the acetolysis of 6-substituted anti- and syn-9-benzonorbornenol brosylates (1 2), and six basis sets from substituent effects in the naphthalene series (2p). The physical property sets include the integrated intensities of the skeletal stretching vibrations of substituted benzenes and ethylenes, the Cl3-nmr shifts at the para carbon position of substituted benzenes and the F-nmr shielding effects of 4'-substituted 4-fluorodiphenylmethanols and 4'-substituted 4-fluorodiphenylme thanes. In the brosylate acetolysis sets, conjugative stabilization of the transition state is geometrically excluded in the syn form, but is anticipated in the anti form (13). That is, on structural grounds, u i is expected to be the parameter of choice for the syn set and u& for the anti set. The available data (for the OMe, Me, C1 and NO2 substituents) do indeed conform to this expectation: 6-Subst.-Syn-9-Ar Norbornenol Brosylate Set (RMS = .77)

4

SD

f

-

.03 .033

OR (RA)

.04

.048

o i -

.07

.089

S&L .02 .031

07@) -

.16 .200

6-Subst.-Aizti-9-Ar Norbornenol Brosylate Set (RMS = 1.34) SD

f

4 -

.06 .045

u~ (BA)

.11 .130

4 -

.28 .208

S&L -

.14 .lo4

"ip,

__

.Ol .05 1

The previous analysis by the dual substituent parameter equation of substituent effects in the naphthalene series provided support for the ug scale, especially for sets involving nonconjugating positions (2p). The available data yield six basis sets which presumably give a critical analysis and, in particular, provide distinctions between conjugative (three sets) and iionconjugative positions (three sets). The results (using the earlier symbolism (2p)) are given in Table X. We regard these results as generally supportive of the expectation that the nonconjugative positions are best fitted by the 0; scale, while the conjugative positions are best fitted by the uK(BA) scale. The few apparent ambiguities which seem to blur this distinction involve sets of relatively low A and RMS values. Katritzky, Topsom, and co-workers (14) have reported correlation of the integrated intensities of the 1600 cm-' benzene skeletal vibration of substituted

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

27

TABLE X Analysis of Naphthalene Series Basis Sets Non-conjugating positions *A.4p. Ionization 4-Substituted-2-Naphthoic Acids (RMS = .505)

SD

f

43 -

O~(A)

OR(BA)

01; -

S&L

32

.04 ,077

.04 .076

.07 .147

.09 .186

.09 .182

.24 .484

*A.7p. Ionization 7-Substituted-2-Naphthoic Acids (RMS = .313, except S & L, .323)

SD

f

.04 ,111

.06 .205

.03 .082

.04 .140

.03 .077

.16 .5 18

*F.6a.Ionization 6-Substituted Quinolinium Ions (RMS = .994, except S & L, 1.052)

SD

f

.06 ,058

.16 .156

.08 .084

.17 .173

.10 .099

.44 .445

Conjugating positions *A.6p. Ionization 6-Substituted-2-Naphthoic Acids (RMS = .361, except S & L, .349) O~(BA)

SD

f

.02 .058

4

.04 .lo5

OR(A)

.10 .285

4

S&L

.06 .172

.02 .063

-

u(P) -

.09 ,251

*C.6p. Rate of Saponification 6-Substituted Methyl-2-Naphthoates (RMS = .832, except S & L, .813)

SD

f

.06 .075

.06 .077

.23 .271

.16 .196

.04 .044

.19 .226

*F.7a. Ionization 7-Substituted Quinolinium Ions (RMS = 1.465)

SD

f

.05 .036

.24 .162

.42 ,289

.12 .082

.06 .042

.28 .193

benzenes and of the 1640cm-' mode of substituted ethylenes with the u i parameter (no u1 dependence). The fittings obtained with this ir data are listed as sets 21 and 22 in Tables VIlI and IX. The fitting achieved by the CJ; scale for both ir data sets is approximately a factor of two better than that obtained for any other parameters. While the fitting with u i is slightly outside of thef'Q .I0 criterion, it seems probable that

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

28

this is associated with the relatively large uncertainties in the data for the weakly interacting substituents. The fittings support Katritzky's conclusions that the U I ~ Iterm is negligibly small ( A = -31.7 for the benzenes; -16.8 for the ethylenes: i.e., -X + -). The notion was also tested that the ir data for benzenes should be used to generate u i parameters which would be more suitable to 14 reactions of Table VIII than the values obtained from the 17 basis sets (Table V). Such a procedure, however, was found to give poorer fits than that achieved by the Table V parameter set. This result suggests again the incursion of the experimental difficulties in the ir data noted above. It is clear, however, that the independent test provided by the ir results does offer further support for a unique u i scale. The C13 shifts at the para carbon position for substituted benzenes (and for fris-p-substituted triphenylmethanols) also support the u i scale as shown by the fitting results of sets 26 (and 27). Set 23 of Tables VIII and 1X gives the fitting results for the F-nmr shifts of 4-substituted-3,5-dimethylfluorobenzenes.Because steric twisting is clearly anticipated for some substituents, e.g., NO2, SMe, and NMe2, only the effects of small or symmetric substituents are considered in the set (specifically, F, Cl, Br, I, Me, CN and NH2). The data of this set are best fitted by ug values by factors in the f parameter of from four to eight. Finally, the fittings achieved with the and methanes (sets 24 F-nmr shifts for 4'-substituted-4-fluorodiphenylmethanols and 25), which involve the p-fluorophenyl tag substituted at fully saturated carbon, also provide critical evidence supporting the ug scale. It may be noted that the results for all available F-nmr shifts of p-fluorophenyl tagged systems are best fitted in accord with the following structural expectations (as presented and discussed in detail subsequently): ug type : diphenylmethanes, diphenyl carbinols, diphenyl ethers UR(BA)

type: benzophenones, biphenyls, diphenylsulfides

u; type: benzophenone adducts of H', BF3, BC13 and BBr3, tripheny!methyl cations. u i type: triphenylmethyl anions

D. rn-Substituent Effects According to earlier considerations, the effects of m-substituents have been considered generally to be of the sigma zero type. Swain and Lupton have questioned this conclusion. We have proceeded in the following manner to obtain evidence on the issue. From all the known data, 1 1 sets of meta substituent reaction series data were found which meet the minimum substituent criterion for basis sets. These reactions are listed in Table XI, with the p y ,p g ,

M

Equilibria

2. cf. Lit. references for Table 11, set 3.

1. cf. Lit. references for Table 11, set 1.

Rate, saponification, ArCO,Et, 60% aq. acetone, 25"

2.367

Rates

.992 Ionization, ArCO,H, H,O, 25" Ionization, ArCO,H, 50% aq. EtOH, 25" 1.454 1.688 Ionization, ArCO,H, 75% aq. EtOH, 25" 1.658 Ionization, ArCO,H, 80%aq. Me cellosolve, 25" 2.360 Ionization, ArOH, H,O, 25" Ionization, ArSH, 48% aq. EtOH, 25" 2.739 2.966 Ionization, ArNHi, H,O, 25" Ionization, 3-X Pyridinium ions, H,O, 25" 6.041 Ionization, 4-X-ZNaphthoicacids, 5O%aq. EtOH, 25" 1.255 Ion-pair formation, ArC0,H-DPG, benzene, 25" 2.175

Reaction

1.129

.403 .620 .726 .827 .440 .839 1.026 2.626 .732 1.031

4

'

.48

.19 .31 .35 .43 .5 8 .47

SO

.4 1 .43 .43

am

Meta Basis Set Reactions. Fits to Eq. (1) with Use of ukValues

14

20 14 14 11 20 9 18 14 8 10

n

.07

.03 .06 .06 .06 .09 .07 .10 .16 .04 .06

SD

.077

.093 .111 .097 .087 ,101 .067 .084 .076 .077 .073

f

2.359

.998 1.413 1.643 1.708 2.307 2.665 2.989 5.936 1.238 2.166

P

3. cf. Lit. references for Table 11, set 5 . 4. cf. Lit. references for Table 11, set 6. 5. (a) Biggs, A. I., and R. A. Robinson, J. Chem. Soc., 388 (1 961); (b) Bordwell, F. G., and G. D. Cooper, J. Am. Chem. Soc., 74, 1058 (1952); Bordwell, F. G., and P. J. Boutan, J. Am. Chem. Soc., 78, 87, 854 (1956); 79, 717 (1957); (c) Kieffer, F., and P. Rumpf, Compt. Rend., 238, 360 (1954); (d) Sager, E. E., et aZ., J. Res. Natl. Bur. Stand., 35, 521 (1945); (e) Kuhn, R., and A. Wasserman, Helv. Chim. Act., 11, 3 (1928); (f) Benkeser, R. A., and H. R. Krysiak, J. Am. Chem. Soc., 75, 2421 (1953); (g) Fickling, M. M., A. Fischer, B. R. Mann, J. Packer, and J. Vaughan, J. Am. Chem. Soc., 81, 4226 (1959); (h) Sheppard, W. A.,J. Am. Chem. Soc., 84, 3072 (1962);85, 1314 (1963); (i) Liotta, C. L., Chem. Comm.,7, 416 (1968). 6. cf. Lit. references for Table VI, set 10. 7. cf. Lit. references for Table VI, set 1. 8. cf. reference 2p. 9. cf. reference 2p. 10. cf. Lit. references for Table 11, set 7. 11. cf. Lit. references for Table XI, set 8.

11.

6. 7. 8. 9. 10.

5.

2. 3. 4.

1.

No.

~

TABLE XI

.03 .06 .06 .06 .09 .07 .10 .16 .04 .06 .07

SD

4

.ll .ll

.04

.147 .059 .lo6

.050

Data for NMe,, SCF, and SF, not included, no R values listed. Data for SCF, and SF, not included, no R values listed.

.10 .05 .20 .17 .15 .25 .12 .06 .12

.09 .03 .ll .11 .13 .24 .09 .05 .13

.174 .046 ,122 .113 .123 .068 .186 .111 .143

.150a .043 .123b .094= .1 1gC .114 .182 .056a .132a

.01 .09

.Olla .160a <.01 .08

.111 .195

.04 .10 .10 .03 .ll .12 .15 .15 .09 .09 -13

.126 .110 .lo0 .135 .081 .082 .050 .I 34 .076 .135 .127

.05 .06 .06 .10 .07 .09 .06 .29

.085 .155 .130 .042 .I09 .090 .098

.03 .08 .08 .03 .10 .10 .12 .ll .07 .05 .10

.093 .111 .097 .087 .lo1 .067 .084 .076 .077 .073 .077

SD

f

S&L SD

f

0;

SD

f

OR(A)

SD

f

OR(BA)

SD

f

a Datum for NMe, not included, no R value listed.

5. 6. 7. 8. 9. 10. 11.

4.

1. 2. 3.

No.

Values of SD and f = SD/RMS for Meta Basis Sets

TABLE XI1

u(m )

.168 .070 ,220 .154 .127 .119 .231 .079 .127

.037 .181

f

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

31

An, n, SD, f values obtained for each on fittings with the u i values of Table V. In Table XII, the comparative values of SD and SD/RMS are given for each of these reactions for fittings to all of the various substituent parameters. As expected from the fact that Am values are small (-.3-.5), the meta data are not discriminating. Three of the eleven meta basis sets are best fit by the u i values (Table XII); two sets are essentially equally well fit by u i and ; two sets are best fit by two sets are best fit by u ~ (; and ~ two ~ )sets are best fitted by the Swain and Lupton parameters. All fits are near the 10% level. Interestingly, the only F value below .I00 is that from the u i fitting. One must conclude from these results that whle the assignment of meta substituent effects to the sigma zero type is not inconsistent, the available meta data provide no sound basis of support for the unique applicability of the u; scale to meta series. Indeed, a scale derived from the 11 meta basis sets does not fit the meta sets significantly better.

E. u i Values Brown and Okamoto have defined u+ based upon the rates of solvolysis of p-substituted t-cumyl chlorides and demonstrated their applicability to a number of “electrophilic type” reaction rates and equilibria (2c, 15). The parameters have also been used by Yukawa and Tsuno in their dual substituent parameter treatment of such reactivities (2g, 16). Unfortunately, however, the t-cumyl chloride solvolysis series does not meet the requirements for a minimal basis set. Only one existing reaction set was found which satisfies this requirement, Eaborn’s protonolysis rates of p-substituted phenyl trimethylsilanes (1 7). Through use of Eaborn’s series, it was found that widely varying sets of u i were generated with very similar precision by use of various assumed constraining conditions, including values of A p . In the absence of independent evidence on the correct value of AP and, in the light of the moderate to poor fits achieved with most of the generated u i sets when applied to other reactions, an alternate procedure has been utilized to obtain the basis u i parameters. The pT values are well defined for both the Brown and Eaborn sets. In view of the approximate but general relationship, p y p y , obtained for other types of reactivities, a similar relationship was assumed. It was then noted that if uI; value were calculated by the relationship p y = p f s p g , or u1; = [log (I?/ k 0 ) / @ ] - of,the results were consistently (irrespective of the value of uf)20% smaller for Eaborn’s set than for Brown’s set. That is, if for Brown’s set APE 1 .OO, then for Eaborn’s set h p Z 30. Using these constraints, averaged ug values were obtained from the two data basis sets. The results were compared with u g , uR(BA)and values. Differences of a few hundredths of a unit found for most +R substituents between .I;, uR(BA)and u i sets were then averaged out (giving the results in Table V) with n o significant loss of precision

t 4

W

17.

15. 16.

14.

13.

10. 11. 12.

6. 7. 8. 9.

5.

II

Arc-CHN; + OAc- + C,H,COCH,OCOMe, HOAc, 40"

+

Protonolysis ArSiMe,, aq. MeOH-HClO,, SO" Solvolysis, ArCMe,Cl, 90% aq. acetone, 25" Solvolysis, Ar(C,H,),CCl, 60% Et,O -40% EtOH, 60" Acetolysis, 2-Ar-2-Me Propanol Brosylates, HOAc, 75" Acetolysis, 6-Subst.anti-9-ArNorbornenol Brosylates, HOAc, 77.6" Decomposition ArN: ArOH, H,O, 29" Coupling ArN; + 2,6-Naphthylamine Sulfonic Acid, H,O, 20" 0

Ionization, Ar,COH, aq. H,SO,, 25" Ionization, Ar,C(C,H,)OH, aq. H,SO,, 25" Ionization, ArC(C,H,),OH, aq. H2S0,, 25" Ionization, ArCHOH*, aq. H,SO,, 25" Ionization, ArC(OH)Me', aq. H,SO,, 25" Ionization, 4-Subst. Pyridinium Ions, H,O, 25" Ionization, ArCO,H, H,O, 25' Equilibrium, A r g + 2 0 H - + ArN, 0-, H,0,25" Ionization Potentials, ArCH,(g), eV.

1.

2. 3. 4.

Reaction

No

-2.317 2.722 2.522

-2.407 -4.086 3.994

-.666

-2.948

-3.902

-.841

-4.498 -4.657 -2.432

-9.793 -7.896 -5.557 1.999 1.981 2.688 .474 5.342 1.082

-5.474 -4.639 -2.718

Rates

-11.100 -8.085 -4.521 1.733 2.260 5.153 .627 6.566 1.045

Equilibria

.79

-.67 .63

.96

.76

.82 1.oo .89

.88 .98 1.23 1.15 .88 .5 2 .76 .81 1.04

Sigma R Plus Series. Fits to Eq. (1) with Use of uiValues

TABLE XI11

.I2 .07 .I4 .02 .25 .I0

6

4

5

4

6

11 12 7

5

6 13 5 8

.042

-.713

.986 2.892

,081 .023 .20 .04

.01

-2.31 8

-3.427

-4.462 -4.714 -2.504

1.909 2.037 2.993 .5 05 6.555 1.115

-5.204

-9.861 -7.844

P

.045

,031

.070 .075 .119

,059 .032 .170 .lo8 .067 ,060 .074 .094 .196

3'

.06

.06

.2 1 .15 .I 3

.75

7 4

5

.55 .23

SD

7

n

W

W

Decomposition ArCON,, Toluene, 65.2" -.140 Rearrangement Ar(Me)C = NOH, 1,4dichlorobutane, -4.440 70" Cannizaro Reaction, ArCHO, 50% aq. MeOH, 100" 4.426 Bromination, Subst. Durenes, MeNO,, 30" -7.839

2.1 27 -7.523

+.134 -3.361 .48 .96

-.96 .76

7

5

5 9 .I4 .27

.o 1 .14 .060 .087

.062 .088 2.249 -7.072

.046 -3.701

1. (a) Deno, N. C., and A. Schriesheim, J. Am. Chem. SOC., 77, 3051 (1955); Deno, N. C., H. E. Berkheimer, W. L. Evans, and H. J. Peterson, J. Am. Chem. SOC.,81, 2344 (1959); (b) Arnett, E. M.,and R. D. Bushick, J. Am. Chem. SOC.,86, 1564 (1964); (c) White, W. N., and C. A. Stout, J. Org. Chem., 27, 2915 (1962); (d) Schuster, I. I., A. K. Colter, and R. J. Kurland, J. Am. Chem. SOC., 90, 4679 (1968); (e) Knuteson, G., and R. W. Taft, unpublished data. 2. References (a), (b), (c), (d) and (e) for set 1. 3. References (a), (b), (c), (d) and (e) for set 1; Diffenbach, R. A., K. Sano, and R. W. Taft, J. Am. Chem. SOC.,88, 4747 (1966). 4. Yates, K., and R. Stewart, Can. J. Chem., 37, 644 (1959). 5 . Stewart, R., and K. Yates,J. Am. Chem. SOC.,80, 6355 (1958). 6. cf. Wells, P. R., S. Ehrenson, and R. W. Taft,Prog. Phys. Org. Chem., 6, 147 (1968). 7. Goodman, J. F., P. Robson, and E. R. Wilson, Trans. Faraday SOC.,58. 1846 (1962). 8. Lewis, E. S., and H. Suhr, Chem. Ber., 91, 2350 (1958). 9. Harrison, A. G., P. Kebarle, and F. P. Losing, J. Am. Chem. SOC.,83, 777 (1961). 10. Eaborn, C., J. Chem. SOC., 4858 (1956); Dean, E. B., and C. Eaborn, J. Chem. Soc., 2299 (1959); Eaborn, C., private communication. 11. Brown, H. C., and Y. Okamoto, J. Am. Chem. SOC.,79, 1913 (1957);80,4964 (1958). 12. Nixon, A. C., and G. E. K. Branch, J. Am. Chem. SOC.,58,492 (1936). 13. Heck, R., and S. Winstein, J. Am. Chem. SOC.,79, 3422 (1957). 14. Tanida., H.., T. Tsuii. - . and H. Ishitobi, J. Am. Chem. SOC..86. 4904 (1964). 15. Crossley, M. L., R. H. Kienle, and C. H. Benbrook,J. Am. Chem. SOC 62, 1400 (1940). 16. Zollinger, H., Helv. Chim. Act., 36, 1730 (1953). 17. Tsuno, Y.,T. Ibata, and Y . Yukawa, Bull. Chem. SOC.Japan, 32, 960 1959). 18. Yukawa, Y., and Y. Tsuno, J. Am. Chem. SOC.,79, 5530 (1957). 19. Husigen, R., J. Witte, H. Walz, and W. lira, Ann., 604, 191 (1957). 20. Tommila, E., Ann. Acad. Sci. Fennicue, A59, 3 (1942). 21. Illuminati, G . , J. Am. Chem. SOC., 80, 4941,4945 (1958); 78, 4975 ( 956).

20. 21.

18. 19.

P

w

-1.53 -3.79

-.612

-1.827 -.569

- .45 1

Pg

-6.247 -7.231 -7.441 -7.914 -1 1.283

-19.43 -8.41

C"-nmr Shifts

-6.419 -7.862 -7.869 -7.913 - 10.746

F-nmr Shifts

-.438

-1.792 -.272

-.680

p4)

12.7 2.22

.97 .92 .95 1.00 1.05

1.40

1.02 2.10

.66

AP

6 6

6 6 5 7 7

11

1.62 .79

.19 .21 .06 .36 .83

.04

.096 .112

.068 -065 .018 .089 .096

.097

.083 .053

.08 .03

8 10

.034

.01

5

f

SD

n

-8.09

-18.36

-6.056 -6.973 -7.249 -8.086 -11.36

-.610

-1.801 -.554

-.640

P

Jones, B.,J. Chern. SOC.,1854 (1936). Smirnov, Y. D., S. K. Smirnov, and A. P. Tomilov, Zh. Org. Khim., 4(2), 216 (1968). Goering, H. L., and R. R. Jacobsen,J. Am. Chem. Soc., 80,3285 (1958). White, W. N., D. Gwyn, R. Schlitt, C. Gerard, and W. Fife,J. Am. Chem. SOC.,80, 3271 (1958). Pews, R. G., Y. Tsuno, and R. W. Taft, J. Am. Chem. Soc., 89, 2391 (1967). Reference for set 26. Reference for set 26. Reference for set 26. Taft, R. W., and L. D. McKeever, J. Am. Chem. Soc., 87, 2489 (1965); McKeever, L. D., Ph.D. thesis, Univ. of Calif., Irvine, 1966. Ray, G. J., R. J. Kurland, and A. K. Colter, Tetrahedron, 27, 735 (1971). Reference for set 31.

Ar,C', H,SO,-H,O, 37" (C of C+center) Ar,C', H,SO,-H,O, 37" (C para t o substituent)

31. 32.

22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.

Arb-FC,H,)CO-BF, Adduct, CH,CI,, 25" Ar@-FC,H,)CO-BC13 Adduct, CH,CI,, 25" Ar@-FC,H,)CO-BBr, Adduct, CH,CI,, 25" Ar@-FC,H,)COH', H,SO,, 25" Are-FC,H,)CC,H:, CH,CN, 25"

O,

26. 27. 28. 29. 30.

25.

--f

Chlorination, ArCOC,H,OMe(-p), 99% aq. HOAc, 20" Cleavage, ArHgBr + HCI ArH, DMF, 17" O-Claissen Rearrangement, ArOCH,CH=CH,, 184.9", (C,H,),O OClaissen Rearrangement, ArOCH,CH=CH,, 181 carbitol

22.

23. 24.

Reaction

No.

TABLE XI11 (continued)

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

35

of fitting. For all -R type substituents, u i are significantly enhanced compared ~ ~ Any ) averaging of these values between to corresponding u i and u ~ ( values. sets is found to be accompanied by significant loss of precision (compare, for example, fittings summarized in Tables IV, VII, IX, and XIV) and consequently is not done in arriving at u i values for -R substituents. The u i values of Table V obtained in the manner described above are found to fit uniquely a substantial number of data sets within the criteria f < .lo. Indeed, the variation of XP and p y values permitted by these correlations is highly remarkable (XP varies from -.96 to 12.0, p y varies from -1 1.10 to -.140 and from t.627 to +6.566). Table XI11 lists values of p y , p$ , XP, n, SD, and f obtained for sets of the u i type, each of which contains data for sufficient numbers and kinds of p-substituents to provide a reasonably critical analysis. Table XIV lists comparative SD and f values for fittings of all the sets of Table XI11 with each of the U, scales of Table V, the F and R values of Swain, and with the single substituent parameter treatment, PO&). These statistics, coupled with structural considerations, we believe support the usefulness and uniqueness of a u i scale of “limited generality.” In general, the f values of Table XIV for the uI; scale are smaller than those of the other scales by factors of from 2 to 10. The root-mean-square F values for the other scales are from 2.25 to 3 to 4 ( S & L, u i , a&,,) times that for u;(. Because this analysis has demonstrated that Swain’s F and R are generally inferior for the discriminating data for all four types, there appears little to encourage proliferation of these parameters.

-

111. DISCUSSION

A. Regarding Fittings by Equation (1)

The fact that our analysis yields essentially the same precision of fit for reaction rates, reaction equilibria, and F-nmr shift data we believe is highly significant. That is, substituent behavior is indicated to be generalizable to a precision of SD/RMS=f = .05 to .lo. This result is in keeping with the basic idea that the substituent effects may, be described by parameters characteristic of the substituent group. To these three types of measurements may be added the C-13 and proton nmr shifts and the ir intensity measurements, for which fittings are generally only slightly less precise. Because the experimental errors in these latter measurements generally appear to be somewhat greater, the generality of the treatment of substituent electronic effects according to eq. (1) is not apparently damaged, but is in fact supported by the broad range of measurements involved.

m

W

SD

.55 .23 .75 .I2 .07 .14 .02 .25 .10 .21 .I5 .I3 .06

No.

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

n i '

.059 .032 .I70 ,108 .067 .060 .074 .094 .I96 .070 .075 .I19 .031

f

f' .loo .206 .337 .196 .142 .I23 .I32 .I68 .339 .I86 .242 .241 .053

SD .88 1.48 1.41 .22 .I4 .28 .04 .45 .I8 .54 .5 1 .27 .I0

OR(BA)

TABLE XIV

1.94 2.23 1.87 .28 .18 .6 1 .04 .49 .21 .9 1 .68 .35 .21

SD

4 .220 .309 .447 .251 .I88 .263 .I48 .I83 .402 .318 .322 .317 .I08

2'

.43

.55

4.59 4.59 3.06 .45 .36 1.19 .09 .77 .30 1.86 1.08

SD

.510 .487 .221

.648

.519 ,637 ,733 .402 .371 .497 .323 .288 .573

f

u s Sets

,JR(A)

Values of SD and f = SD/RMS for

.84 .66 .53 .16 .I3 .41 .03 .51 .19 .55 .69 .32 .I4

SD

.I58 .046 .232 .113 .152 .383 .268 .179 .I38 .I56 .047

.I55 .208

1.40 .33 .97 .12 .15 .89 .07 .48 .07 .47 .lo

.17 .41

.I 1 6a .153a .260a .I47 .131 .195a .I19 .I91 .358 .280a .325 .284 .074

I' SD

"

6 I'

S&L

4

W

14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32.

.045 .081 .023 .042 .064 ,088 .060 .087 .034 .083 .05 3 .097 .068 .065 .018 . I 23 .096 .096 ,107 1.34 2.52 4.40 .79

.48

.21 .08 .06 .31 .34

.02

.03 .o 1 .31 .24 .61

.I3

.I7 .36

.I30 .I45 .071 .090 .I01 .I93 ,107 .I96 .070 .223 .I68 .147 . I 1I .I04 .I45 .312 .293 .259 .I12 .28 .39 .22 .05 .01 .34 .46 .87 .02 .29 .I6 .I 1 .54 .71 .56 1.57 3.10 5.98 1.48

a Datum for NMe, not included, no R value listed.

.06 .20 .04 .01 .01 .I4 .I4 .27 .o1 .08 .03 .04 .I9 .21 .06 .52 .83 1.62 .76 .366 .360 .353 .210

.I71

.208 .I59 .I22 .I56 .I28 .211 .205 .280 .078 .311 .332 .281 .I92 .220

.47 .69 .43 . I3 .03 .66 1.04 1.47 .03 .37 .28 .20 1.05 1.26 1.37 2.36 5.67 11.22 3.95 .355 .281 .244 .370 .231 .408 .461 472 .121 .403 .598 .503 .387 .399 .415 .534 .627 .661 .559 .14 .24 .09 .03 .O1 .34 .04 .86 .01 .38 .09 .08 .7 3 .83 .50 2.07 3.23 2.45 .7 1 .481 .608a .242a .151a

.I51

.I04 .097 .05 1 .089 .05 1 .210 .019a .277 .048 .399 .229a .I98 .259 .257 .07 2.41 .6 1 .07 .I 1 .45 .89 .67 .08 .39 .I2 .I4 .23 .31 .20 .74 1.oo 7.15 1.97

.05 1 .978 .345 .200 .976 .275 .398 .217 .306 .418 .256 .343 .081 ,096 .062 .I 84 .I 17 .421 .278

38

S . EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

The physical property measurements pertain to a specific state of chemical identity, whereas the rate and equilibrium measures pertain to a change between such states. Consequently, eq. (1) is shown t o apply to either situation with essentially equal precision. The data sets with V ’ E p : /py values appreciably different from unity give such large deviations with the single substituent parameter equation (cf. Tables IV, VII, IX, and XIV) that the statistical best-fit parameters are essentially meaningless. However, the data sets with XP values which are either large positive numbers or negative numbers are treated by eq. (1) no differently from those more usual sets (with near unit W values) with respect to both statistics of fitting and of the appropriate structural classification of the type of OR scale giving best fit (cf. discussion of next section). This result provides critical evidence of the general applicability of eq. (1) with the four uR scales. It is important to note that the fitting according to eq. (1) requires zero .OO). While we intercept behavior: i.e., P‘ = .OO for H (for which uI uR recognize that the data for the unsubstituted (H) member of a set may be as subject to experimental error as any other member, such error is generally relatively small for a set of reliable data. Any constant error from this source will be distributed among all of the substituents in such a manner as to achieve “best fit.” Any loss in precision of fitting of the set which may result by such a procedure we believe is a small price to pay compared to the “violence” done by introduction in eq. (1) of a completely variable “constant” parameter. The latter procedure has been utilized by other authors both in treatments by the simple Hammett equation and by the dual substituent parameter equation. We specifically reject the inclusion of a third parameter as a constant intercept in eq. (I), even though the rejection does result in loss of precision fit. Our reasons are as follows. The third parameter gives unwarranted freedom in the fitting of the data. In a data set, the point P=O for the H substituent is a highly critical and valuable one in locating the scale origins. The hydrogen data point cannot influence the rho values (all sigmas are constrained to zero), and accordingly, the hydrogen data point is not explicitly counted in the statistics. Furthermore, the H atom has unique structure (perhaps the most different) among those of all the substituents (10). To in effect throw away this point in a data set (by introducing a third parameter) we believe is to render to the noise level one of nature’s most revealing signals. Many of the significant results of this analysis, which are discussed in the following sections, would have been lost had we not adhered strictly to eq. ( 1 ) . A note regarding the weighting of data by the least-square analysis by eq. (1) is in order. By not explicitly assigning weights to individual points or data sets, we have implicitly weighted the points by the size of the Pi value, or for the individual data set, by its RMS of P‘. This weighting is done because (a) we feel that a larger P is probably generally known more accurately than a smaller one

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

39

(we recognize that there are exceptions, of course) because the P"s are really differences (log k i - log Pi, or Pi - 8)and (b) we have no other knowledge of how to weight points without introducing bias. Consequently, even though our fittings are explicitly weightless, we must make adjustment for our implicit weightings. This adjustment is done by examining the fit parameter, .FSD/RMS: that is, by comparing f values for a given data set as obtained with the various (previously defined) sigma constants. We note here also that the comparison off values among basis sets used to define a particular OR scale is not profitable, because the fitting minimizes the overall SD for all points in all sets considered. Yukawa and Tsuno have discussed (16, 18) a dual substituent parameter treatment having greater freedom than eq. (1). In this treatment, they utilize one universal pi delocalization parameter, 71, and allow p n values for a given data set (one p n value for substituents in the +R class, and the second pn for substituents in the -R class). While this treatment has the potential to correlate data on a very broad basis, it suffers the important disadvantage that it cannot critically distinguish significant separations of polar and pi delocalization effects from nonsignificant or coincidental fittings. That is, eq. (l), as we have applied it, makes the separation of I and R effects by utilizing the noncorrelation between UI and U, values over the full range of electronic effects from extreme -R to extreme +R (in the plot of a, versus any of the OR parameters of Table V, points for a minimal basis set fall in a generally random fashion among three of the four quadrants). With the freedom introduced by the Yukawa-Tsuno treatment, the separation of I-R effects is based upon the noncorrelation between polar and pi delocalization parameters withm each class, -R or +R (i.e., generally within only one quadrant). Because of well established correlations between these parameters for certain common structural features within the -R or the +R classes (lo,), we believe that this treatment at the present level of knowledge does not rest upon very sound ground. (A similar objection applies to the Exner are required for treatment (20).) The present finding that four scales of precise description of p-substituent effects clearly does not appear to support the basic postulate of the Yukawa-Tsuno treatment: namely that a single generalized scale of pi delocalization parameters is applicable within either -R or tR classes.

B. Pi Delocalization Parameters and their Interpretations The UR parameters of Table V show many of the trends previously recognized (24 4, 10, 19). The substituents (-R) having a first row element with an unshared electron pair as first atom (F, OCbH5, OMz, NHCOMe, NHZ and NMez) show enhanced pi delocalization across the scales: i.e., -u: < -uR(BA) < - u i . The increment of the scales is greater between -UR(BA) and - u i than between -ug and -uR(BA), although this trend

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

40

increases sharply in the sequence of substituents given above. For the weaker pi but donor substituents (Me, C6H5, C1, Br, and I) -UR(BA) < - u i -uR(BA) = -ug . For unsaturated substituents containing electronegative atoms (+R), ui(A, > ug Z uR(BA)Z u i is a completely consistent pattern, extending from the weak pseudo-unsaturated substituents, e.g., SCFJ, SiMea, SF5 and CF3, to the relatively strong unsaturated acceptor substituents, e.g., CN, CO1 R, NOz and CH3C0. More specific orders are found in specific instances. Thus N

-oi(A) =

-4< -oR(BA)

for NH2 and OMe, but for F - u ~ ( A ) = -uR(BA)

> -0; .

This special propensity of F for pi donor action in electron-rich systems has been previously discussed (20). For the substituents Me, C1, and Br, -u;;(~, E - u ~ ( -= ~ -~a0R) , but -u: >

for SMe and I. The latter feature has been ascribed t o the presence of unoccupied acceptor orbitals (probably d ) (14). The same relationship may apply for C1 and Br, but the effects are too small to be significant in the definition of the scales. The C6H5 substituent has been considered as having the ~ u) i, values are capacity of either a donor or sink. In accord, u i , u ~ ( ~and negative for C6H5, but u ~ ( A )is positive. Aside from the OH substituent, which was specifically not considered in this analysis becausi of the evidence of marked and specific hydrogen-bonding effects (2b, lo), the only substituent which does not appear to behave acceptably according to eq. (1) is SMe. The behavior of this substituent appears acceptable in all but the u i sets. (The behavior of this substituent in the a; TABLE XV Calculated u i Values for SMe

Reaction

PR

1 3 6 10 11 21 21 28

-9.79 -5.56 2.69 -4.50

-4.66 -7.52 -7.91 -11.28

-.55 -.48 -.66 -.69 -.81 -.64 -.98 -.95

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

41

scale cannot be regarded as well tested, however.) The inadequacy of a fixed u i parameter for the SMe is illustrated in Table XV, which gives values calculated according to eq. (1) for each available set. The inability of a single u i value to describe the behavior of the SMe substituent may be the consequence of two pi interaction mechanisms at sulfur (14,21): e S + - M e

and

+O

E - M e .

However, the iodo-substituent, which might be expected to show similar behavior, is well behaved. The behavior of the substituents MeSO, SCF3, and CF3S0 would be instructive in this connection, but no data exists for these substituents in any of the u i sets. The substituents NHCOMe and OC6H5, which involve competing conjugative interaction mechanisms, as well as coplanarity problems, are only moderately well behaved in the u i sets. Calculated values of c i vary from -.74 to -.86 for the former and -.74 to -.92 for the latter. There is, however, a considerable presumption in the case of the NHCOMe substituent that this behavior is solvent related. The value -.74 (reaction 6 ) is obtained in water solvent at 25", and the value -.86 (reaction 23) is obtained in dimethylformamide solvent at 17". The UR(BA) values calculated for the NHCOMe substituent show similar trends with solvent, as shown in Table XVI. Evidence has been presented from F-nmr shielding effects in m- and p-substituted fluorobenzenes (10) that solvent interaction modifies the uz values of a number of the substituents of Table V (specifically NMez, NH2, NHCOMe, OMe, CH,SO, SF3, CF,SO, CF,, S03ME, CN, COzR, NOz and MeCO). The indicated changes in uI between hydrocarbon and weakly protonic solvents are TABLE XVI Calculated UR(BA) Values for NHCOMe

Reaction

Solvent

PR

u~ ( BA)

1

H,O, 25" H,O, 25" 10%aq. EtOH, 25" 15%aq. EtOH, 25" 50%aq. EtOH, 25" 50%aq. EtOH, 25" dimethylformamide 75%aq. EtOH, 25" 80%aq. Me cellosolve

1 .oo .87 .95 1.93 1.21 1.21 -3.32 1.31 1.44

-.26 -.34 -.33 -.34 -.39 -.39 -.41 - .44 - .46

16 4 28 2 3 40 5 6

S . EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

42

Q.05. In the statistical fittings of reactions, we did not find significant

improvements in correlations utilizing these indicated solvent-effect variations in sigma constants. Consequently, we have utilized throughout this analysis the constants for weak protonic solvents and have allowed any solvent-substituent influences to be reflected in the PI and p R values. This procedure unquestionably oversimplifies the treatment of substituent-solvent interactions (as is indicated by the results for NHCOMe in Table XVI), but when the effects of these interactions are relatively small, the statistical results indicate that the treatment is permissible to the precision we have discussed. For the fittings of p-substituted fluorobenzene F-nmr shifts, the p values do reflect the generally expected effects of methanol-substituent interaction (10) (in cyclohexane, pf = -7.30 and p g = -30.8; in methanol, pf = -9.02 and ppR = -31.2). Additional discussion of solvent effects on p values is given in a subsequent section. In this paper, we have not concerned ourselves with the differing behavior of various alkyl groups, but have instead for the present considered the methyl substituent as roughly representative of the behavior of most alkyl group substituent effects. The present results make possible (through use of pIand pR values) analysis of reported substituent effects of various alkyl groups. Such an analysis is beyond the scope of this paper, however. We infer from the results of our statistical analysis that the four UR scales of Table V are definitive and characteristic of the substituent interacting within a given pi framework. The pi interaction frameworks suggested are as follows (2P, 22):

1. The G: Scale X

o

Y

' X O -Y ,

+-.-.-+

or

-

I (X is a general substituent, Y is a detector or reaction center.) The inclusion of p-substituted fluorobenzene F-nmr shifts in the u i basis sets suggests that weakly interacting Y pi electron donor groups are also permitted.

2. The uR(BA) Scale X

G

Y

- 0.+x-- __._.

Y is a weak to moderate pi electron acceptor group. Examples of Y groups from Table IV include, in addition to carboxylic acid and derivative groups, S02NHR, Se(OH), , As(OH)~, As(OH)~O-, COC6H4F@), S F S , C6H4F@), SC6H4F@), and CH2F. The groups apparently all possess weak pi electron acceptor orbitals. The CH2F group can presumably act as a weak acceptor

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

43

through the contribution of the hyperconjugative form: \----I

-

3. The 0; Scale +

X -O

Y

Y is a strong interacting pi electron acceptor. In addition to carbonium and oxocarbonium ion centers, examples of Y groups from Table XI11 include N l and several electrophilic substitution transition states (cf. sets 10, 21 and 23) of the type

The pyridium ion interaction is also included, although the low hP value (S2) for this ionization (set 6) is in accord with a lesser stabilization of forms, e.g.,

than the corresponding trans quinoidal forms (above), cf. subsequent discussion.

4. The u;i Scale

Y is a strongly pi electron donor group. As previously noted in the results section, examples of Y from Table VI include centers of high pi electron charge density at carbon, sulfur, nitrogen, and oxygen. Also included in Table VI are examples of nucleophilic substitution transition states (cf. reactions 21 and 22) of the type

-.a;, -

It is interesting to note in the latter connection that nucleophilic substitution transition states in which there apparently is not strong delocalization of pi electron density into the substituent tend to fall into the ug type (cf. reactions 18 and 19 of Table VIII). In set 18, there are two ortho nitro groups which apparently take up much of the pi charge (thus it is unavailable to X), whereas in set 19, the positive piperidinium center may cause (perhaps with assistance from the 'NH hydrogen bonding permitted by the aprotic solvent) the

44

S. EHRENSON, R. T.C. BROWNLEE, AND R. W. TAFT

single ortho nitro group to exert a similar influence. Another interesting example of a nucleophilic substitution transition state for which the data clearly discriminates in favor of the u i rather than the UGCA) type is in the methoxydechlorination of cata-substituted 4-chloroquinolines. Evidently, the transition-state interaction structure MeO.. $1

is substantially more important than the structure

as seems reasonable on other grounds. (Compare, for example, pR values for the F-nmr shielding effects of 4-substituted 1-fluoronaphthalenes with 7-substituted lp-fluoronaphthalenes (2p). The fitting results for this rate data set (X-NMe2, OMe, SMe, Me, F, C1, Br, and NO2) are as follows:

4 SD

fa a

.09

.on

~R(A)

.34 .286

UR(BA)

.14 .I20

0;

.31 .260

RMS = 1.20 for all parameters.

It is apparent from these examples (and the previous ones) that the dual substituent parameter treatment appears to provide an important potential means of characterization of aromatic substitution (and other) transition states. C. Concerning OR Type and Values of the p R Parameter

In rate or equilibrium state changes, we presume that generally one state is dominant in determining the OR type (for example, in the ionization of ArNH;, the dominant state is ArNH2, or, in the ionization of ArJCOH, the dominant state is Ar3C+). Because p R values for reaction rates or equilibria are thought to be related to the change in pi electron demand at the reaction center (2,23), there is no necessary relationship between the magnitude of the p~ value and the uR type. Tables 11, 111, VI, VIII, and XI11 show that wide variation in p~ values (and indeed of sign and magnitude of K values) are permitted within each type of OR scale. As noted in the results section, all of the F-nmr shift sets for p-fluorophenyl tagged systems are well behaved in both precision of fit and in

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

45

the structural relationships to the type of UR scale giving best fit. This fact indicates that the measurements of F-nmr shifts in both states corresponding to a reaction equilibrium will provide a revealing probe of the composite equilibrium substituent effect. For the formation of the BC13 Lewis acid adduct of p-fluoro-p'-substituted benzophenones in CH2C12 solution at 25",

substituent effect shifts have been obtained for the adduct state and the uncomplexed ketone state (23). From these, one obtains the substituent effect, f R A, on the state change corresponding to complex formation. These shifts are summarized in Table XVII.

TABLE XVII Substituent Effect F-nmr Shifts for BCI, Adduct Formation with p-Fluoro-p'-Substituted Benzophenones, CH,CI,, 25"

p'-Substituent Me0 C,H,O Me C,H, F

c1

CF, NO2

Uncomplexed ketone, ppm

BCI, adduct, ppm

Complex formation I R A , PPm

.91 .45 .45 .02 -.19 -.52 -1.32 -2.01

5.05 3.66 1.88 I .25 .18a -1.05 -4.25 -6.19a

4.14 3.21 1.43 1.23 .31 -.53 -2.93 -4.1 8

a Calculated shift, using

eq. (1).

The dominant state in the adduct formation is clearly the adduct. Further, the shifts for the uncomplexed ketone are best fitted by the UR(BA), whereas those for the adduct state are best fitted by u i , in accord with structural expectations. Because the adduct state is dominant in the complex formation equilibrium, the I R A values are also best fitted by the u i scale. The PR values for the individual states (summarized in Table XVIII) for this reaction (as well as other similar examples for BF3, BBr3 and H' adducts) are consistent with the idea that increasing pi electron demand at the reaction center increases the -PR

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

46

TABLE XVIII Fitting Results for Lewis Acid Complex Formation (a) Best fit parameter

4

4

Uncomplexed ketonea -2.71

-2.55

1.06

-7.23

-7.86

.92

-5.58

-5.28

1.06

BCI, Adductb IRA ~~~

Best fit parameter

kp

U ~ B A ) 01; 01;

~

(b) Fittings for I R A values ~R(BA)

U i

.22 2.68 .081

SD RMS

f a

.49 2.68 .I82

L

S

UR(A)

;0

.72 2.68 .269

.62 2.68 .233

1.22 2.60 .470

cf. Table 111, set 37 cf. Table XIII. set 25

value. While values for the F-nmr sets generally reflect a similar pattern, there is as yet no satisfactory theoretical model for these terms (2p). An additional example of this kind is also instructive: i.e., the following hypothetical oxidation “reaction”:

As noted previously, the shifts for the methane state (NO. 25 of Table VIII) are best fitted by u i and for the ketone state by UR(BA) TABLE XIX Fitting Results for

SD RMS

f a

--

Values for Oxidation “Reaction”

Ul;b

S&L

.07 .83 .08 1

.06 .52a .121

0

u

~

(

.18 .83 .212

Datum for NMe, not included, no R value. For best fit = -1 .I 62 and p; = - 1.025.

~7

~

~O R )

UR(A)

.27 .83 .324

.5 1 .83 .617

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

47

(Table XVIII). However, the $RA values corresponding to the oxidation reaction state change are best fitted by u i (cf. Table XIX). Thus we see that composite substituent effects for state changes may be complex, with neither state achieving clear dominance. That is, the c r i fitting is apparently characteristic of this particular state change, rather than an individual dominant state.

D. Concerning the Separation of Z and R Effects Data sets for which & /&=X p is very large can potentially provide an indication of whether UR parameters have been correctly defined (i.e., with no, or very little, I effect components). For example, any data sets for which I s 0 for all substituents would give rise to an apparent F’ value of finite value (rather than infinite) if the appropriate type uR parameter were incorrectly defined. In fact, for several such sets of data, the apparent V’ values would be essentially a finite constant. Table XX summarizes the hp values for all data sets having large V values. The results provide no evidence for incorrectly defined u i or u i parameters, because P’ values of Table XX are variable both in magnitude and sign. In the data sets for w h c h h 2 10, there is a considerable presumption that the pr terms may be largely artifacts. That is, for most practical purposes these sets may be regarded as sets with h p + w . One data set from the benzene series has been noted which represents the opposite limit: i.e., AP+ 0. This is the data set of Exner and Jonas (25) for the ionization of X-CH? - @-C02H in 50% aq. EtOH, 25’. There is essentially n o , with discrimination between the precision of fits to the U: , u ~ ( ~or ~u; ) scales TABLE XX kp Values for Data Sets Displaying Large Values

Set No.

AP ui

*15 *16 *21 22 *26 27

PP

p%

Type (cf. Table VIII)

3.46 4.22 -16.8 -31.7 3.9 15.9

-9.02 -7.30 10.1 4.2 -5.5 -1.3

-31.17 -30.82 -1 70. -1 33. -21.2 -21.2

u i T y p e (cf. Table XIII) 29 30

12.0 2.2

-1.63 -3.83

-19.54 -8.46

48

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

t h s data set, and hp values of -.02, -.01, and +.01, respectively, are obtained. The value of py is.903 k .010 with SD= .03 and f =.082 ( X = OMe, C1, Br, I, C6H5, CN, OC6HS, and NHCOMe). This result indicates that the interposed CH2 moiety does eliminate conjugation of the substituent, X, with the ring system (but not necessarily that of the CH2 group).

E. Variables Affecting h The data sets (above) with the large values of X p are physical property measurements which presumably involve predominantly the pi electrons. For example, the F19- and C”-nmr shifts are dominated by paramagnetic contributions resulting from unbalanced pi orbitals (24). Ionization equilibria, on the other hand, are characterized by a much higher blend of polar effects (a blend w h c h traditionally has been defined as hp = 1.00 for the ionization of benzoic acid, H 2 0 , 25’). h values clearly reflect the poorer transmission of pi delocalization effects from the meta than para position. For the select meta sets of Table XI, for example, Am is typically about .4, whereas for corresponding reactions, hp is around unity. Evidence is meager with respect to the ortho position, but it appears that in accord with the classical ideas of pi electron transmission in the benzene ring, generally X p > ho > Am for corresponding reactions (cf. subsequen t discussion). An important feature of eq. (1) is that it allows for the possibility that and PR may be of opposite sign (A = negative quantity). A basic question may be asked: Are I effects transmitted through bonds in such a manner (via direct pi electron transmission or indirect pi-sigma electron interactions) that the I and R effects of any substituent must always necessarily be directly related? The data sets having hP values which are finite negative quantities provide a definite answer of no t o this question. These data sets provide critical evidence that I and R effects may have a high degree of independence. A set with a negative hp is one in which, for example, a substituent with positive values of both urand uR has polar and pi delocalization effects which are opposed: i.e., are opposite in direction. Three reaction rate sets (no. 34 of Table 111 and nos. 15 and 18 of Table XIII) have been found which show this relationship, and the behavior appears quite rational (26). These reactions are such that in going from reactant to transition state, positive charge is moved closer to the substituent (therefore negative values of p y are expected, as observed). These reactions are further characterized by a loss of reactant state para quinoidal resonance stabilization on achieving the reaction transition states. Therefore, because direct resonance effects predominate over indirect or resonance polar effects, positive ppR values are expected, as observed. We have found no data reported for a chemical equilibrium series having

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

49

X p negative. However, there appears to be no reason to expect that such sets should not exist. That is, the absence of such sets is attributable to the lack of imaginative equilibrium studies rather than to any fundamental behavior of nature which prohibits such possibilities (except for u i type p-substituent effect equilibria and meta substituent effects generally, for which positive X values are evidently required). While certain types of structural changes at the reaction center appear to permit AP to take on a high degree of variability, other types of structural change lead to little or no change in X p . Thus, extending the chain of conjugation between the substituted phenyl ring and the reaction center for a given type of reaction with CH=CH or - G C - bonds has little effect on X p (compare the results for corresponding reactions of benzoates, cinnamates, or phenyl propiolates, Tables I1 and 111). Also, the F-nmr shifts for p-fluorophenyl tagged systems are sets with X p 1.0,irrespective of the moiety (a bond, C=O, C=OH+, CH2, CHOH, etc.) interposed between the p-FC61-L, and p'-XC6H4 rings. This result is in marked contrast to the fluorobenzene shifts in which both the F detector and the substituent are placed in the same ring. (Both the Am and X p values are then notably unique (lo).) There is a considerable presumption that steric twisting from coplanarity, which diminishes effective transmittal of pi-electron effects, has appreciable effect on X p . For example, the X p = 1.I0 for the phthalide saponification rate (no. 28 of Table 111) compared with X = .89 for the corresponding benzoate saponification rate is probably a reflection of the rigid coplanarity conditions imposed in the former structure. However, the reactions were carried out in differing compositions of H20-EtOH solvent, so that a solvent effect may also be involved. The ionization of benzoic acids shows a regular trend among basis sets, in decreasing X p values with decreasing water content of the solvent (cf. Table XXI). The decreasing X p values may apparently be ascribed to the decreasing importance of para quinoidal resonance interaction in solvents of decreasing polarity (10,27). However, it is clear from the p y and p g values (both o f which tend overall to increase with decreasing solvent polarity) that additional factors contribute to the solvent effects on these parameters. Additional examples in general agreement with this trend in Ap values for benzoic acid ionizations are found in Table 111. Further evidence supporting this suggested interpretation of the X p values of Table XXI is obtained in the lack of solvent dependence of Xp values for ionization equilibria which involve little or no para quinoidal resonance interaction of the type I -

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

50

TABLE XXI Basis Set Ap Values for Benzoic Acid Ionization Reaction No. Solvent

AP 0%

4

7

1

4

2&3

6

H,O

10%aq. EtOH

50%of EtOH

80%aq. Me cellosolve

75%aq. EtOH

benzene

.87 .95 1.08

.80 1.24 1.55

.84 1.44 1.72

.I5 1.31 1.75

.69 1.36 1.98

~

1.01 (1.00) (1.00)

-

5

-

-

For example, in Table VIII, K values for ionization of ArCH2COzH are .87 k .02 in HzO, 10% aq. EtOH, and 50% aq. EtOH; for ionization of ArCHzNH;, Ap = .99 f .01 in HzO and 50% aq. EtOH. Also, in TableVI, Ap = .80 f .01 for the ionization of ArSH in 48% aq. EtOH and 95% aq. EtOH. Incidentally, the nonunity values for many X p noted throughout all of the correlations of reaction rates and equilibria by eq. (1) may be taken as evidence for the reasonable expectation that various changes in electron demand at the reaction center need not require equal responses of the polar and pi delocalization effects. instead, the nature of the functional group and its chemical change does influence the blend of ZP and RP effects. It is of course probable that in some of the data sets, especially those not fully represented by I OR values, contain experimental substituents with a broad spectrum of Uand errors or small specific effects which have given rise to fortuitous rather than well defined X p values. Clarification can be expected only from more rigorous experimental results for these series.

F. Ionization of Phenols in Water This reaction has been regarded by previous authors as the prototype of ureactions (2,28). It also figured heavily in the definition of the u" parameters of Wepster for -R para substituents (2e). However, we find that the data set for this reaction series is not fitted with acceptable precision by eq. (1) and u ~ ( A ) parameters (SD = .17, f = .130). Nor are the data fitted even as well by other parameters (for uR(BA), SD= .43, f = .329; for S & L parameters, SD = .38, f = .287). Thus, the data for this set appear truly exceptional. The largest deviations for individual substituents in the fitting with u ~ ( A )parameters are found among both -R (NMe2, NHz , F) and +R (NOz and MeCO) substituents. Because the data sets for both m-and p - substituents meet the minimal basis set requirements, we have utilized these in a manner similar to that described for the definition of ug(*) partfmeters to obtain a comparative set of uk(p) parameters.

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

51

TABLE XXII Comparison of u ~ ( and ~ )u&

Substituent NMe, NHZ OMe SMe Me

c1 Br I MeSO SCF SiMe, SF, CF, SO Me CN CO, R NO, MeCO

Parameters

UR(A)

O R (P)

-.34 -.48 -.45 -.I4 -.I I .04 -.45 -.23 -.I9 -.I 1

-.i6 -.25 -.36 -.04 -.06

-

.I4 .14 .20 .11 .38 .33 .34 .46 .41

.04

-.45 -.23 -.19 -.I I .17 .10 .17

.06 .08 .29 .24 .26 .46 .41

We stress that the latter parameter set serves only as a basis of comparison (cf. Table XXII), for we have found no evidence to claim any (even limited) generality for uj;(p) parameters. Table XXIII compares the fits with u i ( p ) and parameters for data sets of Table VI having six or more points. It is to be noted in Table XXII that u ~ ( A )= ui(p) (k.03) only for the halogens, C6H5,%Me3, NOz, and MeCO. It is evident that the uicp) values are appreciably more positive than the corresponding u ~ ( A )for all the other -R substituents (NMe2, NH2, OMe, SMe, and Me). Where differences exist between these two scales for tR substituents, a&) parameters are less positive, however. A clearly anomalous result is the sequence of - u i ( p ) values NH2, NMe2 < OMe < F. There appears to be no ready single explanation of this behavior, especially because the ionizations of phenols in nonaqueous media are satisfactorily (and generally better) fitted by u ~ ( A )parameters (cf. nos. 12, 13, and 14 of Tables VI and VII). It seems likely that concomitant with the strong pi donor action of the 0- reaction center, the protonic H 2 0 solvent may hydrogen bond to substituents, e.g., NMez and OMe, resulting in some twisting of these substituents from ring coplanarity. Such concomitant action would give rise to

52

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

TABLE XXIII Comparison of Fits with u&

and u I Z ( ~ )Parameters

%(P)

UR(A)

NO.^,^

SD

f

SD

I 2 5 7 10

.24 .07 .11 .26 .18 .16 .17 .I5 .31 .35 .62 .10 .38 .41 .23 .04 .19

,133 .042

.03 .03 .14 .14 .03

11

12 13 14 15 16 19 22 23 24 25 26 a

.084

. I 04 .I65 .111 .I 11 ,092 -.I04 .089 .I91 .lo6 . I 33 .158 .068 .094 .223

.08

.10 .10 .28 .36 .7 1 .08 .I 5 .19 .25 .o 1 .I 1

f .o I 5 .018

.072 .058 ,030 ,058 .069 .063 .093 .092 .217 .084 .054

.065 .072 .030 .133

Set no. refers to designation given in Table VI. n is 6 or more for each set, cf. Table VI.

the diminished values of -OR(,,). A limited set of data (n = 7 , and not including either NMez or NH2) for ionization of phenols in 49% aq. EtOH (cf. no. 2 of Table XXIX) is somewhat better fitted by the u;i(p) (f= .044) than by u ~ ( A ) cf= .056)parameters. It is clear that more investigation is required to obtain a better understanding of these interesting differences in substituent effect behaviors. It should also be noted that the ionization of ArNHC6H5 in DMSO (no. 15 of Tables VI and VII) is poorly fitted by the u ~ ( A )treatment cf= .217). This result might be taken 'as an indication of the limitations of u ~ ( A ) parameters in strongly enriched pi electron systems. However, in view of the other successes given in Table VI, we have investigated other alternatives. In the fitting of this data set by the uiCA)parameter treatment, individual substituent deviations of k1.2 log units are obtained for the NOz and SOzMe substituents. Accordingly, fittings were attempted with either the NOz or the SOzMe data point omitted. The results are compared in Table XXIV. It is clear that the data points for both NOz and SOzMe are incompatible with the treatment by eq. (l), as without one or the other, the precision is

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

53

TABLE XXIV Fitting Results for Reaction no. 15 of Table VI with uR(*) Parameters

SD All substituentsincluded ( n = 6) .71 NO, point omitted .I9 S0,Me point omitted .28

f .217 .lo1 .087

5.09 3.83 6.09

4.99 4.04 5.64

.98 I .06 .92

improved to an acceptable level. It appears most likely that the SOzMe substituent shows anomalous behavior. Until this matter is clarified, the fitting parameters (py, p c and h p ) for this reaction obviously must be regarded as highly uncertain.

G. Regarding Independent Generation of uIand OR Parameters It was desirable t o test for possible inadequacy of the uI values for certain substituents. This testing has been done with data for several reaction rate and equilibrium series for which both the p and m- sets meet the minimal basis set requirements. The PR and PI values for the m- and p- positions obtained in preliminary fittings were held as constraints in the data, with the result that both q and UR values were generated from best fitting. These sets of substituent parameters are dependent upon the q values of Table I in one respect only: namely, in the pI and p R values generated by the preliminary fittings as the constraints. This procedure then allows for the detection of any clearly errant substituent parameters. For example, the finite uR values for the CF3 substituent have been questioned (29) on the basis of an errant (too small) value of uI. However, the substituent parameters generated from individual reaction series by this procedure (cf. Table XXV) are in good accord with the values of Table I. Accordingly, the results of this treatment provide no evidence of inadequate or errant u~values. H. “Secondary” uR Values

From the p$ and py values of Tables 11, VI, and VIII, data for additional substituents may be used to obtain the various uR parameters. A number of “secondary” substituent parameters so derived are summarized in Table XXVI. The OR values are rounded values obtained from the indicated data. The uI parameters are based upon m-FC6H4X F-nmr shifts. The results in Table I1 are “untested,” of course, and should be used with due caution.

4

NO,

MeCO CO,R I Br CF, CI F CN

OMe

a

.56 .65

1 .ooo ,286

I .ooo 1.009

.I 2 .09 .04 .I 8 .29 .28 .33 .33 .4 1 .45 .38 .42 .45 .51 .67

.06 .I0 .I2 .23 .26 .27 .38 .30 .39 .44 .45 .46

.so

.oo

-.03

BA. I b

.oo

-.04

OF

1.990 2.167 1.377 .707

2.523 2.302 2.238 .7 30

.45 .44 .5 7 .67

1.781 1.709 1.478 .637

.4 1 .42 .67 .70

.4 3

Constraints

.34 .38

.4 3

.46 .4 1 .45 .48 .53 .65

.26

.25

.40

.08

.oo .I 3 .I 1 .I 7 .22 .26 .24

-.07

.oo

BA. 8b

-.01

BA. 7b

.14

.oo

-.11

BA.6b

Values Generated From Some Basis Sets

rn- andp- basis sets for ionization ArOH, H,O, 25".

Basis sets from Table VI.

From Table I. Basis sets from Table 11.

NH, SMe NHCOMe

C.85

Me H me*

Substituent

UI

TABLE XXV

2.990 2.720 3.100 .710

.27 .23 .27 .39 .42 .47 .47 .40 59 .65

.I8 .I 1 .26

.oo

-.01

A. 1'

2.676 2.426 2.000 .565

.48 .5 1 .52 .67

.23 .20 .31 .42 .46

.I 0

-.01

.oo

-.07

A. l I c

.oo

2.499 2.249 2.526 .468

.21 .24 .22 .45 .4 8 .45 .44 .43 .56 .61

.08 .I 1 .10 .25

-.02

P. I d

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

55

TABLE XXVI "Secondary" Substituent Parameters Substituent OCF, CH,CF, N(CF,), C(OH)(CF,), CF(CF,), SO,NH, CH=CHNO SO,F SO,CF, CH=C(CN), C(CN)=C(CN),

4 -.2Ia -.04e .0oe

.0oe .02e .05' .I 3a

u

~

-.31b (-.04)f

.0Ob coot .02 .0Sh -

~";(A)

~

-.2Ic -.04g

uI

--.21d

.55 .14 .48 .35 .48 .44 .24 .82 .84 .43 .6 1

-

.oog

-

.07' .I 2c -

.5 3d .3Sd .4ld

-

.49g .57! .68! .94'

k

~ O R (P) )

-

-

a Obtained from data of sets 15 and 16 of Table VIII.

Obtained from data of set 2 of Table 11. Obtained from data of sets 1 and 7 of Table VI. Obtained from data for ionization of ArOH, H,O, 25". Obtained from data for set 16 of Table VIII. Suggested value only. Obtained from data of set 1 of Table VI. h Obtained from data of set 1 of Table 11. ' Obtained from data of set 15 of Table VIII. j Obtained from data of set 7 of Table VI. Calculated from meta F-nmr shift relationship: = -7.10 or+ .6 (cf. reference 10). H

7

I. Additional Applications Eq. (1) has potential application t o other types of measurements of substituent effects besides those specifically considered in this paper: e.g., nmr coupling constants and shifts for other nuclei, ir and uv spectral shifts and intensities. We caution (with emphasis) in these applications the needed use of data sets of high quality, both with respect to the precision of the measurement and substituents considered (i.e., a full complement of substituent UI and UR properties must be encompassed for a meaningful correlation to be obtained). There is, of course, no requirement that all data sets will be uniquely fitted by eq. (1) using one of the four OR scales of Table V. For example, the data for the ionization of the conjugate acids of pyridine-N-oxides (30), HzO,25" is found to fit equally well the UR(BA) or ;u scales (SD=.14; f = .072). The data (31) for the rates of alkaline (-OMe) cleavage of ArSnMeJ are not fitted to acceptable precision cfs > .23) by any of the uR parameters. This data set is nevertheless indicated

vI

QI

0.5

Y

-'.O

-0.5

'-.& o;-.

.do

io o;.

/"

Me

= 1.976

.io S'O

PR 10.69 1.355

p,

J

Figure 1. Ion-Pair Formation, ArCO, H + (C, H, NH), C = NH, Benzene 25" ordinate (both figures): log (K/K, 1. abscissa: (upper figure, ub);lower figure, C from UR(BA) scale.

0

- 0.0

zY m0 . 5 1

I.o

"i

-1.0

-0.5

-g 0.0

Y

Y

0

I

-it .o [:

-A0

I

-20

00

.OO .20 40

I

/ I

I

I

1.00

.20

P,;:

PI = 9.30

.60 .80

CN

/..

.40

I

I

Figure 2. Fluorine Nuclear Magnetic Resonance Shifts, ArCH, F, C a , ordinate (bothfigures): &- x, ppm. abscissa: upper figure, u b ) ;lower figure, d from OR(BA) scale.

-0.0

-4*o-/

-4.0

i, 0.0

-

O.ol

.

-.60 "

.60

y

OMe

-20 .OO

O

Me

3 8

N

.20

I

-0.4

.40

I

aoo

2.628

,

.60 .80 1.00

I

x I

I

1.2

a8

p,=2.110 =0.80

PI

0.4

u-

I

0

O U

A u0

1

,

1.8

ub),

Figure 3 . Ionization, ArSH, 48%aq. ETOH, 25" ordinate (both figures): log (KIK,). abscissa: upper figure, a@), uG); lower figure, d from crR(A) scale.

0

Y

\

2.401 I .80

S0,Me

Y

ub),

-.2

-8

1

I

.4

I

.2

.4

1

0

0

-.4

I

.6

I

.8

I

I

.8

I

I

1.6

= 5.855 = 5.03I = 0.06

1.2

Figure 4. Rate, Displacement of CL- by-SC, H, in MeOH, 35" ordinate (both figures): log (klk,). abscissa: upper figure, u@), ub);lower figure, 6 from uR(A) scale.

6.0

58

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

O’O -1.0

1

H.

Me.

Not

CI

-4.0

OMe

1

180

1.0

0.0

2 -1.0 t -3A

I

I

-.a-.40

I

-.20

a

I

I

.40

0.00 .20

/

1

.60

.00

/ &t

OMe

3

-.a-.40

P, ~4.086 p, ‘9.722 *-.66

I

-.20 .OO

.20

I

.40 .60

Figure 5. Rate, Decomposition ArN,’, H,O,29” ordinate (both figures): log (k/k,). abscissa: upper figure, uIip);lower figure, G from u i scale.

to be interesting in that the fittings give values of X p ranging from .27 for the aj&) scale to .01 for the a; scale. The possibility is suggested that this data may reflect unique phenyl anion type pi delocalization effects (3 1). Unique resonance effects of meta substituents in radical cations have been indicated (32). It also seems reasonable that radical reactivities may be treated by a unique set (or sets) of pi delocalization parameters of “limited generality.” The UR parameter scales of Table V appear to be applicable to substituent effects at the ortho and meta positions. For the latter position, however, the data generally are not capable of discriminating between OR scales (cf. earlier results and discussion). For the ortho position, the great difficulty is in obtaining a data set covering the full range of electronic properties without the incursion of substantial proximity effect (2a) contributions. In a following section are reported some of the results of treatment of ortho data sets by eq. (1). Comparative plots are illustrated in Figures 1 through 5 with various

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

59

“ordinary” sigma values and with “synthetic” sigma values (6) obtained (2p) from the best fit to the DSP eq. (1). J. Solvent Effects on p y and

4 in Benzoic Acid Ionization 4

Through use of URR(BA)parameters for benzoic acid ionization, the p y and values given in Table XXVII have been obtained. Two important generalizations are found. For all pure organic solvents (e.g., benzene, n-BuOH, MeOH) p? /py r K 7 2 1.08. In mixed aqueous organic solvents (with the organic component greater than 15%by volume), K? 2 .95 (in H 2 0 and 10%or 15% aq. EtOH, KF = 1.OO). These generalizations hold without exception for all the solvents of sets nos. 2, 3, 5, 6, and 7 of Table I1 and for sets nos. 9, 10, 11, 12, 13, 14, and 15 of Table 111. The same generalizations hold for rates of esterification, ester saponification, and carboxylic acid reactions with diphenyldiazomethane (DPDM): i.e., sets no. 8 of Table I1 and nos. 26,27,34, and 35 of Table 111. It is of interest that set no. 34 involves a novel Ap value (-.37). The greater than unit value of KF in pure solvents is the result expected by the field effect model (33) on a distance basis. The lower than unit value ofK,“ in the mixed aqueous organic solvents appears to be related t o preferential hydration of the reaction center, which results in an increased effective dielectric constant from,the m- compared to the p position. The fact that KY values fall into two separate categories for pure organic and mixed aqueous organic solvents does not support the treatments of Exner (20) or Yukawa and Tsuno (16).

K. Ortho Substituent Effects No properly constituted data sets for reaction rates were found for which eq. (1) is followed with acceptable precision (34). This result may be attributed to the incursion of proximity effect contributions. However, certain benzoic acid type ionization equilibria data sets do appear to follow eq. (1) satisfactorily, although none of the sets qualifies as a minimal basis set. Table XXVII summarizes the results for the fittings with UR‘R(BA)parameters, which for every discriminating set provides the best fit (35). For sets nos. 1, 2, and 3 of Table XXVII, eq. (1) appears to hold for ionization of ortho substituted benzoic acids cf= .048 - .05S), with K; = &/pf = 1.6 .l. This result is reasonable for field effects transmitted only through the molecular cavity: i.e., the lines of force do not pass through appreciable solvent of high dielectric constant (the solvent is presumably excluded by the close proximity of the C02H center and the substituent) (36). It is further of interest that eq. (1) fails for the ionization of ortho substituted benzoic acids in solvents of high OH content (sets nos.4, 5, and 6 of Table XXVII).

*

0" .25 .43 .82

3. Ionization ArCO,H, 73.5% aq. dioxane, 25" 1S O .05 .057 OMe, Me,CI, Br, 1, H, NO, .97 .02 .025 Me, F, C1, Br, I, H, NO, .81 (1 .OO) .02 .041 OMe, Me, F,C1, Br, I, H, NO,

.66 .68 1.22

1.04 .60 1.24

1.03 .62 1.15

2.63 1.51 1.49

f.29 1.48 1.53

2.47 I .34 I .43

mP-

0-

mP-

0-

mP-

0-

P-

m-

.42 .46 .8 I

.45 .41

.07 .05 .04

.060 .059 .047

4. Ionization ArCO,H, 43.5% aq. dioxane, 25" 1.73 .I0 .I 10 OMe, Me, Cl, Br, I, H, NO, .94 .01 ,027 Me, F, C1, Br, I, H, NO, .02 ,040 OMe, Me, F,Cl, Br, I, H, NO, (1 .OO)

P

Me, F,C1, Br, I, H, NO, NMe,, NH,, OMe, Me, F , C1, Br, I, H, CN, NO, NH,, OMe, Me, F, C1, Br, I, H,CN, NO,

2. Ionization ArCO,H, n-BuOH, 25" 1 .I9 .09 .089 OMe, Me, F, C1, Br, I, H, NO, 1.05 .04 .066 Me, F , C1, Br, I, H, NO, (1 .OO) .o 1 .027 OMe, Me, F, C1, Br, I, H, NO,

I .48 1.09 (I .OO)

1. Ion-Pair Formation ArCO,H, -1, 3 DPG, Benzene, 25" .69 .33 .69

Substituents

2.03 .70 1.36

f

2.92 2.15 1.98

SD

0-

KI

PR

PI

Position h

Fitting Results for Benzoic Acid Type Ionization with ffR(BA) Parameters

TABLE XXVll

+

m

.18 .I 1 .44

.4 7 .4 3 .45

.4 3 .03 .03

,239 .051 ,050

.05

.30 .03

,261 .086 .I 10

25" OMe, Me, F, C1, Br, H, NO, OMe, Me, C1, H, NO, OMe, Me, C1, H, NO,

OMe, Me, F , C1, Br, I,C,H,, H, NO, (n = 19) (n = 20)

OMe, Me, F, CI, Br, I, H, NO, Me, F, CI, Br, I, H,CN, NO, OMe, Me, F,CI, Br, I, H , C N , NO,

35% aq. dioxane, 25" .I 98 OMe, F, C1, H, CF,, NO, .220 OMe, F, C1, H, CF,, NO, OMe, F, C1, H, CF,, NO, .217

7. Ionization trans-ArCH=CHCO,H, H,O, 1.02 .03 .I 77 .95 .03 .I44 ( I .OO) .05 .258

1.oo ( I .OO)

I

6. Ionization ArCO,H, H,O, 25"

1.09 (1 .OO)

5. Ionization ArCO,H, MeOH, 25"

8. Ionization Arc<-CO,H, .78 .68 .04 .4 2 35 .06 .95 (I .OO) .07

.38 .26 .9 7

.28 .28 1.01

.28 .84

.oo

0-, rn-, and p-

of set no. 7 for Table 11. reference of set no. 11 for Table 111. 0-, rn-, and p- reference of set no. 10 for Table 111. 0-, rn-, and p- reference for set no. 3 of this table. 0-, rn-, andp- reference of set no. 12 for Table 111. 0-,Kortum, G., W. Vogel, and K. Andrussoco, Pure Appl. Chern., I, 190 (1961). rn- and p , references of set no. 1 for Table 11. 0-, reference for set no. 6 of this table. m-and p , reference of set no. 22 for Table 111. 0-, rn-, and p reference of set no. 21 for Table 111.

0-, rn-, and p- reference

1. 2. 3. 4. 5. 6. 7. 8.

rnP-

.49 .61 .72

0-

rnP

0-

.38 .25 .69

I .oo

1.oo

rnP-

1.oo

.87 .28

3.09

0-

P-

rn-

.01 .42 1.14

4.02 1.48 1.36

0-

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

62

The trans cinnamic acid and phenyl propiolic acid data involve fits of essentially the same precision at a-, m-, and p positions (SD= .05 .02). However, the RMS of these sets is quite low, and consequently, f values of -200 prevail. The interpretation of these results is therefore uncertain. To the extent that the results of Table VII are meaningful, it is of particular interest that KY =p:/pf = .68 for the phenyl propiolic acid, whereas for the trans cinnamic acids, KY = 1.02. These results suggest that in contrast to the ortho substituted benzoic acids, the lines of field forces in the ortho substituted phenyl propiolic acids do (partly at least) penetrate regions of high dielectric solvent. The results for the trans cinnamic acids would then indicate some (but not complete) exclusion of solvent resulting from the presence of the vinyl hydrogens. These interesting results from the application of eq. (1) clearly need to be confirmed by additional studies. ~ values The pi delocalization parameters of Table XXVII show X z p /PI which generally follow the classical sequence hp > hu > Am. There are several exceptions to this trend for A" values, however (sets 1 and 2 of Table XXVII). It is not clear whether these exceptions are significant, or whether they instead merely reflect the difficulty of obtaining ortho data sets which are sufficiently free of incurring proximity effect contributions. The pattern Kf < KF < KY and X p > hu > Am is also clearly shown in the correlation of the proton nmr shifts of substituted phenols in DMSO solution. The 0- and p- substituent effects are best fitted by the parameters (cf. para set no. 24 of Table VI), whereas the rn- substituent effects are best fitted by UR((BA) parameters. The following fitting parameters are obtained from these fits:

*

position

PI

PR

A

KI

SD

f

0-

2.36 1.64 1.45

1.68 .I8

.I1 .47

1.58

1.09

1.63 1.13 1 .oo

.IS .04 .11

.I82 ,056 .I 33

mP-

These correlations are of generally poorer precision than those for reactivity and F-nmr shift data, and in the case of the ortho data set they required rejection of data for the substituents C H 3 C 0 , NOz, and COzR (which give large deviations if included). The latter deviations may be associated with ortho chelation effects. In any case, the K I and h patterns, as noted above, appear essentially as expected. Additional ionization equilibria involving ortho substituents have been reported by Charton (34) to follow eq. (1). The results of our analysis of the data for aqueous ionization of 2-substituted pyridinium ions, o-substituted anilinium ions, and o-substituted phenols are given in Table XXVIII. Comparison with the corresponding meta and para data set results is also included.

W

m

or;

faio;)

0-

mP-

I"(";)

m-

a

"R

3. Ionization Phenols, H,O, 25" 4.06(3.66)b 1.62(1.28)b 2.36 .44 2.48 2.1 8

SD

.17

20

.09(.20)b

.09 20

7

.28 .10 .03

.16 .14

.5 1

4. Partial Rate Factors H-D Exchange Monosubstituted Benzenes, NH,(l) .04 11.52 .48 7 .35 .4 1 7.78 3.22 I .36 7.60 .60 4.55 I .15

.40(.35)b .19 .84

7 18 18

2. Ionization Anilinium Ions, H,O, 25" 5.54 2.76 2.97 1.03 3.09 3.48

.5 0 .35 1.13

n 11 14 13

PR

1. Ionization Pyridinium Ions, H,O, 25" 10.60 1.39 6.02 2.63 5.15 2.69

PI

.I 3 .4 3 .52

A

Fits are indiscriminate; results are obtained with the indicated U R scale Results using the a ~ s c a l e .

mP-

Ia(oR)

OR(BA)

0-

0-

OR

P-

OR

Iaioh)

m-

P-

OR

0-

0 ;

Best fit type

Position

Fitting Results for Other Ionization Equilibria Including the Ortho Position

TABLE XXVIII

.175 .155

.104

.057(.129)b .101 .I 30

.121 .084 .015

.i42 .076 .060

f

S. EHRENSON, R. T. C. BROWNLEE, AND R. W. TAFT

64

While the ortho ionization data are generally fitted with notably poorer precision than for the m- and p positions, there appear t o be characteristic trends indicative of predominant contributions from polar and resonance effects. Thus, for ionization from the ring position (pyridinium ions), XP > Am S ho, whereas for ionization from the side-chain position (anilinium ions and phenols), hp > A" > A". The p I sequence for the former is similar to that for the latter (and for the benzoic acid ionizations of Table XXVII), but the p~ sequence is not. Comparing ionizations from nitrogen, we note

In spite of ionization at a greater distance for the ortho and para positions of the side-chain reaction centers, p~ is greater at these positions for ArNH: than for pyr H". Only at the meta position does p~ reflect ionization at a greater distance in ArNHS than pyr H'. This behavior provides evidence for the much smaller importance of direct quinoidal interaction within the ring than across it: i.e.,

Y'

- X -~

y -_...

+

,

____

- 2 -xQ, x ~

-.a -

In these terms, Shatenshtein's partial rate factors (37) for the H-D exchange of monosubstituted benzenes in liquid ammonia are not anomalous (2m). The analysis of this rate data is included in Table XXVIII. Even though the data are not precise enough to meet the desired standard of precision of fits, the p'; are clearly evident in the results. sequences Ap > Am $=Ao and P:% p;" Consequently, this data set (which is of the u i type) may be taken as providing supporting evidence with the pyridinium ionization (which is of the u i type) for unique h blends for the positions 0- and p - to ionization from the ring position as compared with the X blends for side-chain ionization.

L. Summary A thorough statistical analysis shows that substituent effects (rate, equilibrium, and nmr shifts) in the benzene series cannot be adequately described by either a single or a dual substituent parameter treatment with universal sets of substituent parameters. However, four sets of substituent pi delocalization parameters have been defined utilizing a generalized dual substituent parameter treatment with U I polar effect parameters (eq. 1). These UR parameter sets have been rigorously defended by supporting statistics. Both structural considerations and statistics are shown to support very generally the separation of polar and pi delocalization effects achieved by the use of eq. (1). It is shown, however, that substituent effect sets covering a full compliment of substituent UI and UR properties are critically needed in distinguishing coincidental from significant data fittings by eq. (1).

1. NMe, 2. NH, 3. NHCOMe 4. OMe 5.OC6H, 6. SMe 7. Me 8. C,H5 9. F 10. c1 11.Br 12. I 13. SiMe, 14. MeSO 15. SCF, 16. CF, SO 17. SF, 18. CF, 19. S0,Me 20. CO,R 21. CN 22. NO, 23. MeCO

2

-.83 -1.03 -.79 -.66 .00 -.09 -.32 -.30 -.32 .oo -.01 -.16 -.I7 -.01 .06 .23 .44 .23 .40 .18 -.07 -.lo .49 .70 .73 1.01 1.O1 .54 .81 .72 1.07 .45 .68 I .05 .66 1.29 .78 so .65

1

3a

4a

-.23 -

-.20 -

I .27 1.54

1.82 I .73 1.92

-

-

-

-

-.68 -.25 -.15 -.40 -.03 .31 .61 .68 .63 - .09 1.30 -

-

-1.67 -1.52

-

-

-

-

.9 1 1.14 .67 1.11 1.34

-

-

-

.48

.5 3

so

.26

.35 .56 .60 .59 -

-

-

-.34

-1.05 -1.07 -.21 -.37

-.81

1.10

.22 .38 .38 .38

-.22

-.32

1.18

.25 .39 .4 3 .38

-.21

-.36

(a) Benzoic Acid Type (cf. Tables I1 and 111) Sa 6 7 8 9 10

Data Summary

TABLE XXlX

.82 .96

.17 .30 .37 .36

-.17

-.32

11

.91 1.02

.18 .34 .42 .39

-.18

-.36

12

1.oo 1.17

.23 .42 .47 .45

-.I8

-.32

13

1.14

.21 .39 .43 .45

-.21

-.36

14

1.14

.22 .39 .42 .40

-.19

-.36

15

mw.1 1 Y

d y!

W

I

I

d m ? Y .-.w o

ION

c?

P-9

y!?

e r - 4

I-

N

I

N

?

9

-

r-

1

N

-f

m

I

I

I

z

W

I

I

9 N

I

I

-0

m

I

I

N

w m N 9 I

m

9 I

m

9

c? IO

N

r-

?

0

v

m-m N1" m m

N

NN

I

I

?

m

0

m

d

1 N

-

m

1 3

9?

I

d

c?

mr-

0

N

c?

9 00

-

E:

m

c?

c?

Y

I

m

I

IO

l-

? I

66

rm y!

m

m 09

m "!

W

1

I

m

09

15. SCF, 16.CF,SO 11. SF, 18.CF, 19.S0,Me 20.CO,R 21.CN 22.NO, 23.MeCO

14.MeSO

2.48

.I I

-.46

-.92

-.53 -.56

.lo7 -.60 .096 -.80 .I20

.I52 -1.99 -1.85

4

.42

-.35

-.41 -.23 -.20

.O1

.84 -.27

.40

.013

-.028

.72

.64 .70

.42

.oo

.09 .22 .26 .23

-1.32

7.69 8.10

.34 .45 -2.95 .02 -.19 -2.83 -.52 .49 .99

.34 -2.01

.05 .10

-.I4 -.05

38

.91 -1.19

-.I0

5.0C6H, 6.SMe 7.Me 8. C6H, 9.F 10. c1 1 1 . Br 12.I 13. SiMe,

2.19

-.60

-.I8

-.066

1 . NMe,

35

2.NH, 3.NHCOMe 4.OMe

34 2.34 .5 3

40

-1.26

-3.09 -2.86

42b

-2.33

.36 -.64

1.96 2.49

1.20

.43

.93 - S O

41

-1.02 -2.24 2.85 -2.14 -3.64

-.go

-.I4 .45 .30 -.78

-3.15

39

(a) Benzoic Acid Type (cf. Tables I1 and 111)-conr.

33

37

32

36

30

31

TABLE XXIX-COH~.

m

9 I

“dv)

9999

s

W

u!

I

W

9 I

b,

I

m

9

m m 71

Y

z

m w ?.?

e 9

09

v)

COP-

I

W

I

9

?-.

I

s

vlm 6‘0

I

t-

10

9

t

I

w

9

w m m m

9-11

0,

1

QI

1. NMe, 2. NH, 3. NHCOMe 4. OMe 5.0C6H, 6. SMe 7. Me 8. C,H, 9. F 1o.a 11. Br 12. I 13. SiMe, 14. MeSO 15. SCF, 16. CF,SO 17. SF, 18. CF, 19. S0,Me 20. CO,R 21. CN 22. NO, 23. MeCO

-6.35 -5.90 -8.85 -7.15 -10.25 -10.35 -7.65

-

15.05 14.05 5.15 11.45 7.25 4.50 5.55 2.80 6.40 2.70 2.10 1.35 -.65 -4.80 -

15

18

2.02 -3.29

17

-3.00

-

71.6 40.8

-

-

-14.7 -9.2 -14.2 -20.6 -21.8 -1 1.3 -23.1 -29.0 -25.8

.O

18.4 40.4 34.8 .O -1 7.2 .O -

56.8 48.2 33.1 13.2 12.7 45.3 28.8 30.7 29.4

-

70.7 62.0

-8.95

5.57 2.29 1.83 1.45

4.15

12.84

(b) Sigma Zero Type (cf. Table VIH-cont. 19 20 21 22 23

.21 11.70 1.25 -2.26 -1.60 7.45 4.40 -.82 .20 .63 -.97 5.40 .32 .10 3.00 6.80 .79 -.52 3.10 .9 3 2.60 .98 1.06 1.08 1.70 -SO -3.00 -4.12 -7.50 -5.35 2.72 -5.05 -1.85 -8.00 2.96 2.86 -5.90 3.77 -8.80 4.61 -1.43 -9.01 -2.79 -6.10

15.90 14.40

16

TABLE XXIX-cont.

- 1.44

-.78

-.69

-.23 -.37

.12

.1 I -.23 -.43

.19

.5 3

25

.23

.65

24

-6.0 -4.2

-4.4 -3.0

6.0 3.6

3.9

2.8 4.4 2.0 1.o .4

8.8

11.9

27

8.1

11.8 9.5

26

r-

m

I

I

c! d

W

I

I

t 3

I

d

? I

?

m

r-

I

I

c?

\q

'?

c?

m

m

I

I

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72

1. NMe,

3. NHCOMe 4. OMe 5.OC6H, 6. SMe 7. Me 8. C,H, 9. F 10. c1 11. Br 12. I 13. SiMe, 14. MeSO 15. SCF, 16. CF,SO 17. SF, 18. CF, 19. S0,Me 20. CO,R 21. CN 22. NO, 23. MeCO

2. NH,

-.17

-.04

-.11

-.11

-.07

.20 .09

-.14 -.15

-.66

18

.45

17

-3.62

-1.56

.96 .62 -.40 -.82 -.87 -.67

2.20

19

3.34

1.03

-.62

-.90

-3.45

20

-5.51

.66 -.84 -1.21 -1.10

2.99 2.73

5.21

21

-.51

-.07 -.16 -.17

.13

-1.34

-.82

-.42 -.22

.56

1.10 1.44 .90

-.13 -.22 -.23 -.18

.02

.05

.14

.48

.98 .92

-.36 -.40 -.21

-.28

.01 .02

.24 .16

.92 .35 .55

(d) oh Type (cf. Table XII)-conr. 22 23 24 25

TABLE XXIX-conf.

-3.60

-.54

1.79 1.12

4.38 3.26

26

-4.25

-1.05

1.88 1.25

3.66

5.05

27

-4.20

-.85

2.21 1.48

5.41

28

-6.78

-3.80

.52

.83 -.45

-4.85

-.50

8.82 4.25 8.30 3.02

19.85

30

6.10 3.30 5.75 2.38

29

-2.1

7.9 6.9

7.1

18.6

34.9

31

-4.9

3.3 2.5

2.7

7.8

13.8

32

21 P

1. NMe, 2. NH, 3. NHCOMe 4. OMe S.OC,H, 6. SMe I. Me 8. C, H, 9. F 10. c1 11. Br 12. I 13. SiMe, 14 MeSO 15 SCF, 16. CF,SO 17. SF, 18. CF, 19. S0,Me 20. CO, R 21. CN 22. NO, 23. MeCO

.4 3 .60 -37 .56 .72 .38

-.15 -.16 .21 .I2 .25 .15 -.07 .06 .34 .37 .39 .35 -.04 .5 2

1

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-.13 .02 .44 .4 7 .5 1 .4 4

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.60 55

.58

-.19 -.12 .23 .10

-.14 -.08 .23 .I1

3

2

.98 1.19

.78 1.02

.56 .64 .66 .58

1.74 1.36 1.93 1.04 1.86 2.14 1.03 1.86 .85

1.88

-.02

.99

1.42 1.05 1.58 .66 1.38 1.62 .79

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1.26

1.02 -99 .94

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.34

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.I0 .11

(e) Meta Sets (cf. Table XI) 5 6 7

-.33

4

TABLE XXIX-cont.

2.12 3.86 4.03 1.99

.90 -.46 .4 1 2.24 2.40 2.36 1.92

-33 .75 .40

8

.86 .92

.40 .38 .34

1.30 1.56

.68 .SO .80 .79

1.66

1.55

1.56

.72 .80 .79 .71 -.36 1.26

.21 -.23

.13 .12 -.02

-.13

-.36 -.24

-.37 -.33 -.13

-.13

11

10

9

3

3

c!

c!

d

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'

a Unpublished data sets of A. S. Hoefnagel, M. A. Hoefnagel, R. H. de Vos, and B. M. Wepster. Ionization of Pyridine N-Oxide Conjugate Acids, H,O, 25". Ionization ArCO, H, n-BuOH (cf. reaction 15 of Table 111). Ionization ArCO, H, 73.5% aq. dioxane (cf. reaction 10 of Table 111). Ionization ArCO, H, 43.5%aq. dioxane (cf. reaction 9 of Table 111). Ionization ArCO, H, MeOH (cf. reaction 12 of Table 111). g Ionization ArCH=CHCO, H, H, 0 (cf. reaction 22 of Table 111). H, 35% aq. dioxane (cf. reaction 21 of Table 111). Ionization Arc=-CO, f Ionization &OH, H, 0,25". J Ionization ArOH, 49% aq. CTOH, 22". Rates of methoxide cleavage of ArSiMe,, 50". P-nmr shifts for ortho substituted phenol (OH) in DMSO. Ionization 2-subst. C, H, N@, H, 0, 25". Ionization o-subst. C, H, N q ,H,0, 25". Ionization o-subst. C, H, OH,H, 0, 25". p Ortho log. partial rate factor D substitution in C, H, X,NH, (1). Same as p meta position. r Same as p para position.

78

S. EHRENSON, R T. C. BROWNLEE, AND R. W. TAFT

Evidence is provided by this analysis that (a) structural considerations discriminate among at least four practical classes of pi delocalization behavior, each of which has “limited generality”; (b) the blend of polar and pi delocalization effect contributions to the observed effect of a substituent is widely variable among different reaction or data sets (the contributions may be opposite as well as alike in direction), depending upon structural considerations and the nature of the measurement; (c) solvent may play an important role in determination of the observed blend of effects; (d) it is the first three conditions which lead to the deterioration of the single substituent parameter treatment as a means of general and relatively precise description of observed electronic substituent effects in the benzene series. The potential of eq. (1) in the elucidation of transition-state structure is discussed briefly. Also, a number of additional applications of the method which require further study of the preliminary conclusions or suggestions are pointed out.

Acknowledgment We are greatly indebted to Prof. B. M. Wepster for making available to us his unpublished data (cf. sets 3 , 4 , 5 of Table 11, and sets I , 4 , 5 of Table VIII).

References 1. This work was supported in part by the National Science Foundation (UCI) and the U.S. Atomic Energy Commission (Brookhaven). 2. For previous treatments, cf. the following: (a) Hammett, L. P. Chem. Rev., 17, 125 (1935); (b) Jaff6, H. H., Chem. Rev., 53, 191 (1953); (c) Brown, H. C., and Y.Okamoto, J. Am. Chem. Soc., 79,1913 (1957); (d) McDaniel, D. H., and H. C. Brown, J. Org. Chem., 23, 425 (1958); (e) van Bekkum, H., P. E. Verkade, and B. M. Wepster, Rec. Truv. Chim., 78,815 (1959); (4Taft, R . W., and I. C. Lewis, J. Am. Chem. SOC.,81,5343 (1959); (g) Yukawa, Y., and Y. Tsuno, Bull. Chem. SOC.Japan, 32, 965,971 (1959); (h) Roberts, J. L., and H. H. Jaffk, J. Am. Chem. SOC.,81, 1635 (1959); (i) Taft, R. W., J. Phys. Chem., 64, 1805 (1960); (j) Palm, V., Russ. Chem. Rev., 31, 471 (1961); (k) Wells, P.R., Chem. Rev., 63, 1 7 1 (1963); (1) Ehrenson, S.,Prog. Phys. Org. Chem., 2, 195 (1964); (m)Ritchie,C. D., and W. F. Sager, Bog. Phys. Org. Chem., 2, 323 (1964); (n) Charton, M., J. Am. Chem. SOC., 86, 2033 (1964); (0) Exner, O., Collection Czech. Chem. Commun., 31, 65 (1966); (p) Wells, P. R., S. Ehrenson, and R. W. Taft, Prog. Phys. Org. Chem., 6, 147 (1968); (4)Swain, C.G., and E.C. Lupton, Jr., J. Am. Chem. SOC., 90,4328 (1968); (r) Hammett, L. P., Physical Organic Chemistry, McCraw-Hill, 2nd ed., 1970, Chap. 11. 3. (a) Taft, R. W . , J. Am. Chem. SOC.,79, 1045 (I 957); (b) cf. also references 2(1), p. 244 and 2(p),,p. 19 1 , for background discussions. 4 . Taft, R. W., in N. S . Newman, Steric Effects in Organic Chemistry, Wiley, New York, 1956, Ch. 13; cf. reference (3a), footnote (4), for clarification of symbolism.

SUBSTITUENT EFFECTS IN THE BENZENE SERIES

79

5. cf. references 2(fl and 2(h); E. D. Schmid, et aL, Spectrochim. Acta, 22, 1615, 1621, 1633,1645,1659 (1966). 6. Rakshys, J. W., R. W. Taft, and W. A. Sheppard, J. Am. Chem. Soc., 90, 5236 (1968). 7. (a) References 2(a), 2(c), 2(e), and 2(f); (b) R. W. Taft, S. Ehrenson, I. C. Lewis, and R. E. Glick,J. Am. Chem. SOC.,81, 5352 (1959). 8. The u, values of Table I represent slightly modified values from those given previously. Modifications were based upon examination of more recent data for ionization equilibria involving substituents at saturated carbon: (a) Ionization of XCH,CO,H, H,O, 25", XSF,, Ray, N. H., J. Chem. SOC., 1440 (1963); X=SCF, and CF,SO, Orda, V. V., L. M. Yogupolskii, V. F. Bystrov, and A. U. Stepanyants, J. Gen. Chem., 35, 1631 (1965); (b) Ionization of 4-substituted [ 2.2.2.1 octane-] carboxylic acids, 4-substituted bicyclo [ 2.2.2.1 octa-2-ene-1-carboxylic acids and dibenzobicyclo [ 2.2.2.1 octa2,5-diene-l-carboxylic acids, 50% aq. EtOH, 25", Baker, F. W., R. C. Parish, and L. M. Stock, J. Am. Chem. SOC.,89, 5677 (1967); (c) Ionization of 4-substituted bicyclo [ 2.2.2.1 octane-I-ca~boxylicacids and 4-substituted bicyclo [2.2.1] heptane-1-carboxylic acids in 50% aq. MeOH, 25", Wilcox, C. F., and C. Leung,J. Am. Chem. SOC.,90,336 (1968). 9. Fawcett, F. S., and W. A. Sheppard,J. Am. Chem. SOC.,87, 4341 (1955). 10. Taft, R. W., E. Price, I. R. Fox, I. C. Lewis, K. K. Andersen, and G. T. Davis, J. Am. Chem. SOC.,85, 709, 3146 (1963). 11. Angelelti, J. M., R. T. C. Brownlee, A. R. Katritzky, R. D. Topsom, and L. Yakhontov, J. Am. Chem. SOC.,91,4500 (1969). 12. We are indebted to Dr. Douglas Blagdon for drawing our attention to these data. 13. Tanida, H., Y. Hata, S. Ikegami, and H. Ishitobi, J. Am. Chem. Soc., 89, 2928 (1967). 14. (a) Brownlee, R. T. C., A. R. Katritzky, and R. D. Topsom, J. Am. Chem. SOC.,87, 3261 (1965); (b) Katritzky, A. R., R. F. Pinzelli, M. V. Sinnott, and R. D. Topsom, J. Am. Chem. SOC.,in press. IS. Brown, H. C., and Y. Okamoto, J. Am. Chem. SOC.,80, 4980 (1958). 16. Yukawa, Y., Y. Tsuno, and M. Sawada, Bull. Chem. SOC.Japan, 39, 2274 (1966). 17. (a) Eaborn, C., J. Chem. SOC., 4858 (1956); (b) Dean, E. B., and C. Eaborn, J. Chem. Soc., 2299 (1959); (c) Private communication from Professor Eaborn. 18. Presentation of Professor Y. Yukawa at Second Linear Free Energy Conference, Irvine, California, March 1968. 19. (a) Brownlee, R. T. C., and R. W . Taft, J. Am. Chem. SOC.,90, 6537 (1968); J. Am. Chem. SOC., 92, 7007 (1970); (b) Taft, R. W., N. C. Deno, and P. S. Skell, Ann. Rev. Phys. Chem., 9, 287 (1958). 20. (a) Streitwieser, A., Jr., and H. F. Koch, J. Am. Chem. SOC.,86, 404 (1964); (b) McKeever, L. D., and R. W. Taft,J. Am. Chem. SOC.,88,4544 (1966). 21. (a) Craig, D. P., J. Chem. SOC., 997 (1959); (b) Bordwell, F. G., and P. J. Boutan, J. Am. Chem. SOC., 78, 87 (1956). 22. Taft, R. W.,and J. W. Rakshys, Jr., J. Am. Chem. SOC.,87, 4387 (1965). 23. Pews, R. G., Y. Tsuno, and R. W. Taft,J. Am. Chem. SOC.,89, 2391 (1967). 24. (a) Ramsey, N. F., Php. Rev., 78, 699 (1950); (b) Pople, J. A., and M. Karplus, J. Chem. Phys., 38, 2803 (1963). 25. Exner, O., and J. Jonas, CON.Czech. Chem. Commun., 27, 2296 (1962). 26. (a) Bunnett, 3. F., and E. Zahler, Chem. Revs., 49, 273 (1951); (b) Lewis, E. S., and E. B. Miller, J. Am. Chem. SOC., 75, 429 (1953); (c) Dickson, J. D., and C. Eaborn, J. Chem. SOC., 3036 (1959). These authors first point out that the rates of aqueous

80

27. 28. 29. 30. 31. 32. 33. 34.

35. 36.

37.

S. EHRENSON, R. T.C. BROWNLEE, AND R. W. TAFT decomposition of p and m-substituted phenyldiazonium salts could be described by an equation of the form of eq. (1). Gutbezahl, B., and E. Grunwald, J. Am. Chem. SOC.,75, 559 (1953). cf., however, reference 20. Holtz, D.,Prog. Phys. Org. Chem., 8, 55 (1971). Nelson, J. H., R. G. Harvey, and R. D. Ragsdale,J. HeFero. Chem., 4, 591 (1967). Eaborn, C., H. L. Hornfeld, and D. R. M. Walton, J. Chem. SOC.(B), 1036 (1967). Latta, B. M., and R. W. Taft, J. Am. Chem. SOC.,89, 5172 (1967). Kirkwood, J. G., and F. H. Westheimer, J. Chem. Phys., 6 , 5 0 6 , 5 13 (1938). Charton, M., Prog. Phys. Org. Chem., 8, 235 (1971) has reported extensively on correlations of rate data for ortho substituted benzene derivatives using the dual substituent parameter treatment in the form with an additional (intercept) parameter, and in our opinion, too limited substituent data sets. For these and related reasons which we have discussed, we question the significance of many of Charton’s correlations. M. Charton has summarized his earlier correlations of these data in reference 35. Our results are dissimilar to those of Charton for the reasons indicated. (a) Charton, M., and B. I. Charton, J. Org. Chem., 33, 3872 (1968); (b) Bowden, K., N. B. Chapman, and J. Shorter,J. Chem. SOC.,5239 (1963); (c) Bowden, K., M. Hardy, and D. C. Parkin, Can. J. Chem., 46, 2929 (1968). Shatenshtein, A. I.,Adv. Phys. Org. Chem., I , 155 (1963).

Substituent Effects in Nonaromatic Unsaturated Systems By Marvin Charton Department of Chemistry. Pratt Institute. Brooklyn. New York 11205

CONTENTS

I . Introduction . . . . . . . . . . . . . . . . . . I1. Substituents on Carbon-Carbon Double Bonds . . . . . . .

A . Substituted Vinyl Sets . . . . . . . . . 1. DipoleMoments . . . . . . . . . 2. Ionization Potentials . . . . . . . . B . VinylideneSets . . . . . . . . . . . 1. Equilibria . . . . . . . . . . . 2 . Reaction Rates . . . . . . . . . . 3 . Physical Properties . . . . . . . . . c. trans-Vinylene Sets . . . . . . . . . 1. Equilibria . . . . . . . . . . . 2. Reaction Rates . . . . . . . . . . 3. Physical Properties . . . . . . . . . D . cis-Vinylene Sets . . . . . . . . . . 1. Equilibria . . . . . . . . . . . 2 . Reaction Rates . . . . . . . . . . 3 . Physical Properties . . . . . . . . . E. Reactions of Carboncarbon Double Bonds . . . 1. Charge Transfer Complexes . . . . . . 2. Addition Reactions . . . . . . . . . a. Electrophilic Addition . . . . . . . b . Nucleophilic Addition . . . . . . . c . Radical Addition . . . . . . . . d . Carbene Addition . . . . . . . . e. Diels-Alder Cycloaddition . . . . . . f . 1,3.Dipolar Cycloaddition . . . . . . I11. SubstituentsonCarbon-Heteroatom DoubleBonds . A . Substituted Heterovinyl Sets . . . . . . . B. Heterovinylidene Sets . . . . . . . . . C. Heterovinylene Setswith Heteroatom Reactionsites D . trans-Heterovinylene Sets . . . . . . . . E . cis-Heterovinylene Sets . . . . . . . . . F . Amidines and Carboxylic Acids . . . . . . 1. Amidines . . . . . . . . . . . . 2. Carboxylic Acids . . . . . . . . . . . . . . . . . . . a. Equilibria b . Reaction Rates . . . . . . . . . 81

. . . . . . .

. . . . . . .

. . . . . . .

. . . . . . .

. . . .

. . . .

. . . .

. . . .

. . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . .

. . . . . . . . .

. . . . . . . . .

. . . . .

.

. . . . . . . . . .

. .

. . .

. . . . . .

. . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . .

82 86 86 86 90 90 90 93 93 94 94 94 97 97 99 105 106 107 108 108 108 120 121 126 126 132 132 133 135 137 144 146 146 146 146 149 151

82

MARVIN CHARTON

IV . Substituents on Carbon-Carbon Triple Bonds . . . . . . . . A . Substituted Acetylene Sets . . . . . . . . . . . . B Ethynylene Sets . . . . . . . . . . . . . . . . 1. Properties of the Ethynyl Proton . . . . . . . . . . 2. Other Ethynylene Sets . . . . . . . . . . . . . C. Reactions of Carbon-Carbon Triple Bonds . . . . . . . . V . Substituentson Carbon-HeteroatomTripleBonds . . . . . . . A. Substituted Nitriles . . . . . . . . . . . . . . . B . Heteroethynylene Sets . . . . . . . . . . . . . . VI . Substituents on Cyclopropane Rings . . . . . . . . . . . A. Substituted Cyclopropane Sets . . . . . . . . . . . B . Cyclopropylidene Sets . . . . . . . . . . . . . . C. trans-Cyclopropylene Sets . . . . . . . . . . . . . D. cis-Cyclopropylene Sets . . . . . . . . . . . . . E. Reactions of Cyclopropane Rings . . . . . . . . . . . VII . Substituents on Heterocyclopropane Rings . . . . . . . . . A. Substituted Heterocyclopropyl Sets . . . . . . . . . . B . Heterocyclopropylidene Sets . . . . . . . . . . . . C. Heterocyclopropylene Sets . . . . . . . . . . . . . D . Heterocyclopropanes with Heteroatom Reaction Sites . . . . . VIII Substituents on Other Unsaturated Systems . . . . . . . . . . . . . . . . . . . . . . . . . . A . Pyridones B . Quinones . . . . . . . . . . . . . . . . . . C. Multiple Substitution at Nonequivalent Sites . . . . . . . D. Conjugated Dienes and Polyenes . . . . . . . . . . . E . Allenes and Cumulenes . . . . . . . . . . . . . . IX . Conclusions . . . . . . . . . . . . . . . . . . A . Transmission of the Electrical Effect . . . . . . . . . . B . Composition of the Electrical Effect . . . . . . . . . . C. Other Conclusions . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . Appendix 1. Substituent Constants from Sources Other than Reference 23 and Reference 29 . . . . . . . . . . . . . . Appendix 2 . Data Used in Correlations . . . . . . . . . . . .

.

.

. .

. . . . .

. . . . .

. .

. .

. .

. . . . . . . .

. . . . . . . .

. . . . . . . .

. . . .

. . . . . . . .

. .

. . . .

.

. .

. .

151 151 154 154 156 156 156 157 157 160 160 163 163 164 164 164 164 164 164 165 166 166 166

173 174 175 175 175 181 181 182 189 192

I . INTRODUCTION Linear free energy relationships (1-9) have been of great utility in the quantitative study of reactivity and of physical properties as a function of structure . In the study of carbon compounds. attention was first directed to mand p-substituted benzene sets (1.2.4) . The application of linear free energy relationships to compounds bearing the substitutent on an sp3 hybridized carbon atom has been reviewed (3) . Reviews have appeared on the application of the Hammett equation to ortho-substituted benzenes (10). naphthalenes (1 1). and heteroarenes (12) . No systematic review of the application of linear free energy relationships to nonaromatic unsaturated systems has appeared as yet. although these compounds comprise a large fraction of the known organic

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

83

compounds. It is the objective of this work to provide a critical survey of this field. The first mention in the literature of the application of the Hammett equation to a nonaromatic unsaturated system seems to be a private communication from Carter to Evans and DeHeer (13) reporting a linear relationship between the Hammett up constants and the Eo values of substituted quinones. No details were given. Jaffi (2) had suggested that rigid molecules might be treated by means of the Hammett equation. In accord with the proposal, Harnsberger, Cochran, and Szmant (14) attempted the extension of the Hammett equation to pKa data for X'X2C=NNH2, where X was methyl, phenyl, or substituted phenyl. The first clear-cut example of the application of the Hammett equation to nonaromatic unsaturated systems is the work of Charton and Meislich (15), who reported the correlation of pKa data for trans-3substituted acrylic acids, trans-3-substituted-2-methylacrylic acids, and trans-3substituted-2-carboxyacrylic acids with the Hammett equation by means of the up constants. This work was followed by that of Hine and Bailey (16, 17), who reported a correlation of the rates of reaction of trans-3-substituted acrylic acids with diphenyldiazornethane by means of the up constants. This effort was followed by a report by Charton (18) that pKa data for substituted acetylenic acids were correlated by the up constants. Charton (19) has also reported correlations of data for substituted cyclopropanes and substituted cyclopropane carboxylic acids with the Hammett equation. Since 1964, a number of other papers have appeared demonstrating the applicability of both the simple Hammett equation

Qx =pox + h

(1)

and the extended Hammett equation

Q = ~ U I , X+P%,x + h

(2)

to various sets of data for nonaromatic unsaturated systems. Of the two equations, the extended Hammett equation, first proposed by Taft and Lewis (20),is the more widely useful, because it accommodates the complete range of substituent effect composition. The simple Hammett equation can be adapted to substituent effect composition only in a crude manner by the proper choice of substituent constant. To clarify this point, we must consider what is meant by the composition of the electrical effect. Taft (21) has suggested that the electrical effect of a substituent is composed of localized (inductive and/or field) aqd delocalized (resonance) factors. Thus we may write the substituent constant of the group X as OX = hUI,X

&uR,X

(3)

MARVIN CHARTON

84

We had previously described the composition of the electrical effect by means of E , where

E = SIX

(4)

Substitution of eq. (3) into eq. (1) gives

equivalent to eq. (2) with a = pX, 0 = pS. Then

E = PIa We believe that a more useful measure of the composition of the electrical effect may be defined as

where

PR

is the percent resonance effect. Furthermore,

The quantities E and PR are related to each other by the expression

E . 100 pR=E+1

(9)

Values of pR for the substituent constants commonly used with eq. (1) are given in Table I. When correlations are made with eq. (l), the substituent constant used determines the composition of the electrical effect.

TABLE I Composition of the Electrical Effect in Substituent Constants Substituent Constants "I am 0 ;

"P "P

"P "R

PR

0 25 40

50 62 60 100

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

85

As the extended Hammett equation is capable of accommodating the complete range of electrical effect composition, it will be used in this work. The question then arises of what substituent constants to choose for the localized and delocalized effects. Recently, Swain and Lupton (22) have proposed a new separation of electrical effects into localized and delocalized factors. Although they have proposed new localized effect substituent constants, they agree with most other workers in the field that the UI constants are a valid measure of the localized effect. They have, however, proposed a new set of delocalized (resonance) effect parameters, and they have suggested that the UR values are not pure resonance effect parameters. In our opinion, the Swain-Lupton treatment is invalid for the following reasons: (a) The separation proposed by Swain and Lupton depends upon values of u, and up for Me3" which are reported by McDaniel and Brown (23). These authors have reported probable errors of +.2 for these substituent constants. It seems to us that parameters based on values so much in doubt are of little use. (b) The separation of Swain and Lupton is based on the assumption that the trimethylammonio group is independent of resonance interaction: that is, the resonance effect of this substituent is zero. The trimethylammonio group is isoelectronic with the tertiary butyl group, which has been firmly established as an electron donor by resonance. We would therefore expect that the trimethylammonio group should also be an electron donor by resonance. In accord with this expectation, a value of ut of -.15 obtained from infrared spectra of para-disubstituted benzenes has been reported for the trimethylammonio group by English, Katritzky, Tidwell, and Topsom (24). This result is supported by values of -.11 for U R obtained from pKa measurements (25) and of -.08 for ug obtained from "F-nmr data for p-fluorotrimethylanilinium chloride (26). A value of -.12 for OR can be calculated from pKa values of substituted phenols (24,27). These results are in value determined for the trimethylammonio group (4). agreement with the Additional support for an electron don& delocalized effect by the trimethylammonio group comes from the observation of the effect of NR; groups on benzenoid chemical shifts (28). It was suggested that the results indicate a somewhat higher electron density at the position para to the NR', group than at the meta position. In view of the above arguments, we have continued to use the substituent constants as a delocalized effect parameter. Correlations in this paper have been made therefore with 01 and OR constants. The UI values were generally taken from the compilation of Charton (29), and UR values were obtained from the equation OR = Op-UI (10)

ui

where use was made of the up values reported by McDaniel and Brown (23). Other substituent constants used will be reported in Appendix 1. The correlations were carried out by means of multiple linear regression analysis (30).

86

MARVIN CHARTON

11. SUBSTITUENTS ON CARBON-CARBON DOUBLE BONDS

Foremost among the classes of the nonaromatic unsaturated systems is that of compounds in w h c h the substituent is bonded to a carbon-carbon double bond. It is convenient to divide the data sets for carbon-carbon double bonds into five categories: vinyl, vinylidene, trans-vinylene, cis-vinylene, and reactions of carbon-carbon double-bond sets.

A. Substituted Vinyl Sets Certain physical properties of substituted ethylenes may be correlated with the extended Hammett equation. Included in this category are dipole moments and ionization potentials.

1 . Dipole Moments The first recorded correlation of dipole moments with substituent constants was observed by Taft (3), who reported results for alkyl cyanides, chlorides, iodides, and tertiary amines. Kross and Fassel (31) have reported the correlations of dipole moments for 4-substituted nitrobenzenes with the simple Hammett equation. Rao, Wohl, and Williams (32) have studied the correlation of dipole moments of &substituted benzenes with eq. (1) and of monosubstituted benzenes with the equation PX = Pb,,xl

(1 1)

Van Beek (33) proposed the equation

C)

log - =pox for the correlation of dipole moments. This equation has been criticized by Exner (34), who points out that it fails for px = 0. Exner has himself proposed the equation -+---+

PX = P I ~ I , X U I , X+ P R ~ R , x % , x *+Po

(13)

for the correlation of dipole moments. In this relationship, 4 is the distance between charges due to the inductive (localized) effect and dR the distance between charges due to “polar conjugation”; ug signifies the use of u& for electron donor substituents and u< for electron acceptor substituents. This equation is based on the resolution of p into localized (PA) and delocalized ( p s ) components, a concept inherent in the mesomeric moments defined by Sutton (35) as (14) &n = pArX - PAlkX

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

87

Sharp and Walker (36) have reported “good linear plots” of px - p~ for 3- and 4-substituted pyridines, pyridine-N-oxides and nitrobenzenes against the appropriate substituent constants. Charton (37) has reported correlations of dipole moments for substituted ethylenes and related compounds with eq. (1) using the UI, urn and up constants. Best results were generally obtained with up. Only those substituents which are symmetric with respect to the substituent-to-carbon bond are included in the sets studied. In this manner, the problem of the conformation of the substrate was avoided. All of the sets studied may be written in the form XGZ, where X is the substituent, Z is a constant substituent, and G is the skeletal group to which Xpand Z are bonded (in this case, the carbon-carbon double bond). For the trans-vinylene sets, members of the set for which up,x> up,z were considered positive, whereas members for which up,x < up,z were considered negative. For the vinylidene sets, members of the set for which luP,xl> luP,zl were considered to have the sign of uP,x, whereas members of the set for which luP,xl < luP,zl were considered to have the same sign as that of up,z. The quantity which is really of interest in the correlation of sets bearing a constant Z substituent is the moment of the X group, px. This quantity is given by the expression pX

= p Z - Ebbs

(15)

where k b s is the observed dipole moment and pz the group moment of the constant Z substituent, which is equal to the moment of the compound ViZ. Applying eq. (2) to eq. (15) and solving for Ebbs gives Ebbs

= - c r ~ ~ X - P ~ R , X - h + ( l l ~ I , Z + P ~ R+, hZ

(16)

or as Z is constaot, /Jobs = a‘U1,X +P’OR,X

+h’

(17)

equivalent to eq. (2). Thus, correlations have been carried out directly with observed dipole moments through use of eq. (2). The quantity of interest in the case of the vinylidene sets is again px. From the law of cosines, we obtain px = -pz

COS

8 f d & b S - SinZ8 p i .

(18)

For vinylidene sets, 8 is approximately 120°, and p X = 0 . 5 pz *d/&s-O.75p&.

(19)

For Z with small values of pz@z < S), pX zEbbs

As for the vinylidene sets studied here, pz is small. These correlations were carried out with the Ebbs values. The sets studied are given in Table 11. Results of the correlations are set forth in Table 111.

MARVIN CHARTON

88

TABLE I1 Vinyl Sets ~

Q

Set 2-1 2-2 2-3 24 2-5 26 2-1 2-8 2-9 2-10 2-1 1 a

Substrate

Substituted ethylenes trans-2-Substituted styrenes trans-3-Substitutedpropenes Ir 2-Substituted-1-bromoethylenes Ir 2-Substituted-1-chloroethylenes P 3-Substituted acrylonitriles P 2-Substituted propenes Ir 1-Substituted styrenes Ir 2-Substituted 1,3-butadienes Substituted ethylenes I trans-3-Substitutedpropenes Dipole moment. Ionization potential. Ira

Ir

’fh

Reference 31 31 31 31 31 31 31 31 31 41 41

The significance of r is <90% CL unless otherwise noted. The confidence levels for the significance of regression are reported as superscripts on F values. Confidence levels for the significance of a,0, and h are reported as superscripts on the values of s,, sp, and Sh. Of the nine sets correlated with eq. (2), seven gave significant correlations. The other two sets each had only four members. Undoubtedly, had more data been available, significant results would have been obtained for ali sets. The composition of the electrical effect in these sets is reported in the form of the pR values in Table IV. Most of the sets studied show a value of pR of 42, which corresponds roughly to that of the up” substituent constants. It has been shown (38) that for correlations with the simple Hammett equation (eq. 1) of sets having a constant substituent Z, PZ = P l 2 u Z + P H (20) where pz is the value of p for the set bearing the constant substituent, PH is the value for the set which bears n o constant substituent (the set for which the constant substituent Z = H) and p l z is the coefficient of the interaction term (39). In the case of the extended Hammett equation [eq. (2)], the equations analogous to eq. (20) are

The results obtained for the correlation of a and 0 values of sets 2-1 through 2-4 are not significant. Thus, eqs. (21) and (22) are not obeyed in the case of dipole moment data.

4.64 4.62 5.58 5.07 6.21 3.75 1.27 1.32 .6 11 .769

5.50

4.70 6.06

LY

3.34 4.68 3.93 3.33 3.31 6.13 3.55 4.72 1.13 1.66 2.51 2.29 1.70

P

7.O7tlg 42.08e 4.611' 45.95'

11

99.5%CL. 99.0% CL. 98.0% CL. 97.5%CL.

d

.36Se .982g .786g .370g 1.30rn .472e .997rn .120g .491g .273e .38On .112'

.550e

SLY

80.0% CL. 50.0%CL. O 20.0% CL. p <20.0% CL. Number of points in set.

*rn <90%CL.

90.0%CL.

' 95.0%.CL.

.038

.057

.482 .267 .613 .260 .0975 .398 .293 .233 .0378 .452 .218 .194 .0554

.I25 ,013 .314 .781. .891J .788 ,328 319 ,823 .051 .156

40.48e 176.2e 16.139 29.32' 196.9e 41.75' 58.78f 34.19'

.949 .993 .930 .975 .996 .994 .983 .993 .9995 .674 .936 .869 .989

.0930 .0473 .414 -1.29 -1.39 -3.80 .344 .198 -.0309 9.75 9.85 9.46 9.33

d

Sest

re

Fb

Ra

h

a Multiple correlation coefficient. F test for significance of regression. Partial correlation coefficient of 01 on OR. Standard errors of the estimate, a,p, and h. 99.9% confidence level (CL).

2-1 2-2 2-3 2-4 2-5 2-6 2-7 2-8 2-9 2-10 2-10A 2-11 2-11A

Set

TABLE III Results of Correlations with Vinyl Sets

3.92" .717g 2.39". .196J .580h .361e .861k .266'

.fillJ

.863g .521e 1.48J 2.1Sg,

spd

.227' ,166' .376" 2.15" .060Se .387k .184m .223' ,0287" .160e .0922e .Ille .0387e

sg

7 4 5 20 15 6 5

4

12 8 8 6 6

nq

MARVIN CHARTON

90

TABLE IV Composition of the Electrical Effect-Vinyl Sets Set

PR

Set

pR

Set

PR

Set

PR

2-1 2-2 2-3

42 44 42

2-4 2-5 2-6

42

2-1

'

2-10A 2-llA

66 69

a

2-8 2-9

23

In this set, 01 = f(UR). Correlation for this set was not significant.

2. Ionization Potentials

A number of correlations of ionization potentials for substituted benzenes (40-42), benzyl (43), phenoxy (44), and alkyl (45) radicals and substituted pyridines (46)with the simple Hammett equation have been reported. Charton (47) has studied the application of the extended Hammett equation to substituted ethylenes and carbonyl compounds. The sets studied here are reported in Table I1 (sets 2-10 and 2-1 1). Results of the correlations are set forth in Table 111. The results obtained are much improved by the exclusion of the values for X = Cz H3, Ac, F, H and OAc from set 2-10 (set 2-10A) and the value for X = H from set 2-11 (set 2-11A). The composition of the electrical effect corresponds to that found for the ui constants as is shown by the PR values reported in Table IV. B. Vinylidene Sets We have classified the available vinylidene sets into three categories: equilibria, rates, and physical properties. 1 . Equilibria

Charton (48) has examined the correlation of pKa values for 2-substituted acrylic acids with the Hammett equation. This work was extended by Sandris (49). Data exist for nine sets of 2-substituted acrylic acids. In eight of these sets, the substrate bears constant substituents. These data have been correlated with eq. (2): the sets studied are set forth in Table V. The results of the correlations are reported in Table VI. Seven of the nine sets studied gave significant correlations, and only two of these sets gave significant values of 0. Unfortunately, of those sets which gave significant correlation with eq. (2), only set 5-1 contains an electron acceptor substituent. Thus, with regard to the composition of the electrical effect, only the pR value of set 1 is meaningful.

”

a

5-5 5-6 5-1 5-8 5-9 5-10 5-11 5-12 5-13 5-14 5-15 5-16 5-17 5-18 5-19 5-20 5-21 5-22

54 ”

I,

91

trans

,.

,,

,,

1,

”

7,

11

9,

2-Substituted acrylic acids a-Substituted-cis-cinnamic acids

Substrate

trans-1-Substituted-2-chloroethylenes ” 1 ” 2-bromoethylenes ” 2’ ” styrenes ” 1 ” propenes ” 1 ” ” 3 ” methylacrylates ” 1 ” lbutene-3-ones

MeAc 2 : 3 EtOH-H2O

H,O

H2O 50% V/V EtOH-H2O

50% V/V EtOH-H20

H2O

Solvent

Parameters for the calculation of chemical shift in nmr spectra. Chemical shifts in nmr spectra. Frequencies, nmr spectra.

SH 6H

YC

6H 6H

6H 6~ 6H

VC

6H

”

a ” ” crotonic ” 2 ” -3,34imethylacrylic acids kr 2 ” ally1 chlorides 103kr 2 ” vinyldielthylphosphates 2; Substituted ethylenes

’

pKa

5-1

5 -2

5-3

Q

Set

Vinylidene Sets

TABLE V

KI H,Ot

Reagent

20 85

51 56 56

56 56 56

56

55 56

53

48 48 50 49 48 50 49 48 51 51 52 54

25 25 25 25 25 25 25 25

25

Ref.

T“C

h)

W

5-6 5-7 5-8 5-9 5-10 5-11 5-12 5-13 5-14 5-15 5-16 5-17 5-18 5-19 5-20 5-21 5-22

5-5

5-1 5-2 5-3 54

Set

P h

a

For footnotes, see Table 111.

-4.14 -.873 4.31 -3.39 1.89 3.90 -2.22 3.03 5.36 -3.00 1.53 5.06 -4.25 -2.92 4.47 -3.81 -1.22 5.77 -3.85 -1.40 5.60 -3.55 -.925 4.66 -3.56 2.16 4.72 -.845 -1.23 -.656 3.31 -7.82 -.0518 ,583 1.24 -.166 -.189 1.38k -.417 43.4 -78.1 338.0 .421 -1.08 -.487 .814 -.920 -.527 -1.01 .789 -.833 -.663 -.278 -.933 -1.27 -.312 -.lo7 -21.4 119. -203. -1.01 1.37 -1.40 8.48 -4.15 -.707

a

.994 ,974 .992 .991 .966 .9995 .998 .999 ,924 .968 317 ,489 .601 .716 .458 ,615 .615 .321 .559 .932 .697 .992

Ra 174.0e, 27.34' 31.351 56.60' 28.06' 527.3' 288.4: 262.2' 5.858' 7.511' 1.005' 3.142k 1.414' 3.148' .798' .609' .6 10' ,460' 1.823' 3.322' 2.362' 30.19'

Fb

.256 ,781 .859 .778 .760k .859 .778 329 ,792 .859 .785 .214 .215 .014 .198 ,174 .lo5 ,250 ,250 .177 .039 .773

rc

d

sa

sb

:234e .353k .144 .283 ,855' 2.33" .814h 2.08h ,203 .166 .519' 1.38" .643g 1.07k ,248 .0511 .206' ,525" .0735 .229' .610m .0591 .251j ,566" .449 1.42m 3.88O .0624 .251m .640" .648 3.49'. 5.60" .408 .494' .332O .473 .74gp .877m 21.4 42.9" 34.2k .590 .853" 1.31' 1.02O 1.76O ,448 .452 1.04" 1.85O ,550 ,793" 1.13p SO2 .724m 1.03' 11.7 24.4' 46.9" .690" .821m .383 .125 .65Sk 1.09k

d Sest

Results of Correlations with Vinylidene Sets

TABLE VI

.353k .234e .202' .144e .15ge .05 1og .063Se .0467g .311g .0622' .582' .168g .300" 18.3e .336" .282" .289m .307h .281° 12.9' .224g .113m

d Sh

11 11 4 8 4

5

9 5

9

7 4 5 4 5 4 4 23 8

5

7 6 4

nq

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

93

Values of pR are given in Table VII. The mi value obtained for set 5-1 seems to show that the substituent effect in the vinylidene position is predominantly a localized effect. Further data are necessary to firmly establish the composition of the electrical effect. TABLE VII Composition of the Electrical Effect-Vinylidene Sets Set

pR

Set

pR

Set

5-1 5-2 5-3 5-4 5-5

17

5-6 5-7 5-8 5-9 5-10

a

5-11 5-12 5-13 5-14 5-15

a a

41

a

a

pR

a

Set

5-16 5-17 5-18 5-19 5-20

pR

Set

pR

5-21 5-22

b

a p was not significant for this set.

Correlation was not significant for this set.

2. Reaction Rates Only two sets of rate data are available for vinylidene substitution, and each set is minimal, consisting of only four points. It is not surprising then that significant correlations were not obtained for these sets. The problem of vinylidene rate data has received very little attention. Further investigation in this area would be very welcome. 3. Physical Properties The only physical property which has been studied for substituted vinylidene sets is the nmr chemical shift of the vinylidene proton in substituted ethylenes and in frans-l,2-disubstituted ethylenes. The first attfmpt at correlating chemical shift data for substituted ethylenes with the Hammett equation appears to be the work of Banwell and Sheppard (53), who reported a correlation of A, values with the CJRconstants, the A2 values being defined by the equation

where 6 ~ 6, ~ and , 6~ are the chemical shifts of the vinylidene, trans-vinylene, and cis-vinylene protons respectively. Eleven sets of chemical shift data were correlated with eq. (2). The sets studied are shown in Table V, and the results of the correlations are reported in Table VI. Only in one set were the results significant (set 5-12), and even in this set, correlation was very poor. It seems certain that no meaningful relationship

94

MARVIN CHARTON

exists between substituent constants and the chemical shifts of vinylidene protons. Unfortunately, no data are extant on any other physical property of vinylidene compounds, such as infrared spectra. This area is again one which would repay investigation.

C. trans-Vinylene Sets We shall again classify the available data into the categories of equilibria, rates, and physical properties. 1. Equilibria The work of Charton and Meislich (15) has already been referred to. Hogeveen (58) has reported a correlation of pKa values for trans-3-substituted acrylic acids. Hogeveen (50) and Sandris (49) have studied the pKa values of p-substituted cinnamic acids. Bowden (59) has also studied pKa values of trans-3-substituted acrylic acids. Data for 10 sets of pK values have been correlated with eq. (2). The sets studied are set forth in Table VIII: the results of the correlations are given in Table IX. Of the ten sets studied, eight gave significant results. Particularly important is the excellent correlation obtained for the trans-3-substituted acrylic acids in water. This large set (16 members) includes a wide range of substituent type. The composition of the electrical effect, as indicated by the values of pR reported in Table X, is 48%. This value is comparable to the composition of the electrical effect in the ionization of 4-substituted benzoic acids. The value of pR for the sets bearing constant substituents will be expected to differ somewhat from this value if eqs.(21) and (22) are obeyed. The sets available are insufficient to test eqs. (21) and (22) by correlation. It would be interesting to study an extensive series of pKa values for trans-3-substituted acrylic acids in various solvents to determine whether pR is independent of the medium, as is the case for the 4-substituted benzoic acids. 2. Reaction Rates

As was noted previously, Hine and Bailey (16, 17) have obtained correlation of rate data for the reaction of trans-3-substituted acrylic acids and diphenyldiazomethane with the Hammett equation. Bowden has reported correlation of rate data for the reaction of trans-3-substituted acrylic acids with diphenyldiazomethane (59) and the alkaline hydrolysis of trans-3-substituted methyl acrylates (69) with the Hammett equation. Sufficient data are available for nine sets of rate studies. The sets studied are reported in Table VIII. The results of the correlations are given in Table IX. Of the nine sets studied, seven gave

8-11 8-12 8-13 8-14 8-15 8-16 8-17 8-18 8-19 8-20 8-21 8-22 8-23

8-3 84 8-5 8-6 8-7 8-8 8-9 8-10

8-1 8-2

Set

a

”

P

”

”

” ”

”

methacrylic cis-crotonic ,,
9,

”

”

7,

”

”

..

”

”

4 ” vinylacetic ” 3 ” l-aza-[2,2,2] -bicycle2-octenes ” 3 ” ethylacrylates ” 3 ” ” ” 3 ” acrylicacids ” 3 ” ” ” ” 3 ” ” ” ” 3 ” ” ” ” 3 ” ” ” ” 1 ” 3chloropropenes ” 1 ” 3 ” 1 ” methylacrylates Substituted ethylenes

”

P

”

>> 39

”

P

”

$

”

”

”

”

3 3

t-BuOH EtOAc EtOH 50%EtOH-H,O CCl,

EtOH

OHOHMeOH Ph,CN,

25 18.8 35 30 30 30 30 25 25

25 25 25 25 25 25 25 25

25 25

55

70 69 69 16 59 59 59 71 71 69 54 53

50,58,62 60 63-6 50 50 49 62,64,67 68

59,60 61

Reagent T”C Ref.

Chemical shifts. Frequencies, nmr spectra.

70% v/v dioxane-H,O MeOH EtOH

50% v/v EtOH-H,O

HZO

HZO 80% Methyl cellosolve-H,O 50%v/v EtOH-H,O

tmns-3-Substituted acrylic acids ,, ” 3 ” 7.

Solvent

Substrate

Infrared spectra frequencies. Parameters for the calculation of chemical shift in nmr spectra.

Q

trans-Vinylene Sets

TABLE VIII

8-6 8-7 8-8 8-9 8-10 8-11 8-12 8-13 8-14 8-15 8-16 8-17 8-18 8-19 8-20 8-2 1 8-22 8-23

8-5

a

-2.26 -2.59 -1.44 -2.58 -2.84 -2.94 -3.44 -2.95 -1.18

8-1 8-2 8-3 8-4

P 4.35 6.65 5.22 4.63 4.56 4.10 5.37 5.3 1 4.33 11.02 -1.14 1.43 1.11 .00757 .0808 -.364 -.691 .438 .793 1735. .0556 -.0416 339.

h

For footnotes. see Table 111.

-2.09 -3.34 -4.27 -2.65 -3.43 -4.09 -4.90 -3.76. -1.47 -5.75 2.33 4.88 2.83 3.85 3.59 .22O -.954 1.16 1.63 1.62 1.60 2.18 2.09 3.03 2.97 -5.19 -8.80 -7.81 -14.5 15.9 48.9 .892 2.11 -1.35 -3.38 51.8 188.

a

Set .997 .9995 .962 .991 .994 .851 .997 .970 .982 .998 .9997 .986 ,857 .973 .998 .992 .994 .637 .559 .977 .874 .873 .829

Ra 1148e 485.9 24.60g 83.20f 172.9e 2.632' 96.1 gk 16.OOk 40.31g 261.5: 841.7' 51.66f 5.512k 36.10f 462.3e. 64.30: 79.23' .341' .228' 31.34g 32.49e. 8.00lJ 6.607'

Fb

.017 .065 .5 39 .038 .324 .896 .859 .7 78 .525 .657 .116 .374 .122 .205 .122 .778 .778 .819 .819 .374 .214 .215 .014

rc

.0553 .0442 .262 ,116 .0896 .291 .0717 .185 .0498 .lo2 .0391° .187 .I78 .138 .0452 .0694 .0894 1.50 2.71 2.28 .361 .470 33.1

.058l: .O12OJ .52d .245g .159e 1.51m .288k .5 78' .131g .30lg .l08' .394g .288' .230g .0730e .216h .27gg 6.41' 11.6' 4.81' .437k .744m 66.3"

d SLY

d Sest

Results of Correlations with trans-Vinylene Sets

TABLE IX

Sh

.0762e .0190e .159' .0227g 1.09h .178e .0706e .377g .318e .0515e 3.39" .245g .736k .O71Sg 1.54m .160e .276h .036Se .763k .0789e .178' .0209h .137g .508g .3540 .129g .367' .088p .0326k .0897e .0599' .576k .0773h .742' 15.4O 1.43p 27.8O 2.59p 1.66e 6.19g .148O .294e .872h .298p 52.8h 28.3e

$

4 6 7 7 7 5 5 4 4 6 23 8 9

5

4 5 6

5

16 4 7 6 7

nq

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

97

TABLE X Composition of the Electrical Effect-trans-Vinylene Sets Set ~

pR

Set

48 56 75 51 55

8-8 8-9 8-10 8-11 8-12 8-13 8-14

pR

Set

pR

Set

pR

8-15 8-16 8-17 8-18 8-19 8-20 8-21

50 51 51

8-22 8-23

78

~~

8-1 8-2 8-3 8-4 8-5 8-6 8-7

a

59

55

63 52 42

a a

75 70

CQrrelation was not significant for this set. p was not significant for this set. a and p differ in sign: therefore, correlation was not significant. (Y was not significant for this set. a

significant correlations. The two sets which did not give meaningful results involve the solvolysis of trans-1 -substituted-3-chloropropenes.As the solvolysis of benzyl chlorides is frequently not correlated by the Hammett equation, these results are certainly not surprising. The value of pR for these data in general is about 50,as is shown by the values in Table X. It is interesting t o note that the value of pR observed for the reaction of the trans-3-substituted acrylic acids with diphenyldiazomethane in EtOH, t-BuOH, and EtOAc is independent of the solvent, according to Bowden’s data. The comparatively high value of pR for the alkaline hydrolysis of the trans-3-substituted ethyl acrylates probably results from the small size of the set (four points). The composition of the electrical effect is in general comparable to that of the analogous 4-substituted benzene sets. 3. Physical Properties The infrared absorption frequencies of trans-3-substituted methyl acrylates gave a significant correlation with eq. (2). The value of pR obtained is 75, which indicates predominance of the resonance effect. Three sets of nmr chemical shifts also were studied. All three sets gave significant correlation with eq. ( 2 ) . The values of pR obtained in two of the three sets were 70 and 78. Again, the resonance effect appears to-predominate.

D. cis-Vinylene Sets There is an obvious structural analogy between cis-vinylene sets, 1 , and ortho-substituted benzene sets, 2. The possible existence of proximity effects in

MARVIN CHARTON

98

a: 2

1

ortho-substituted benzenes was proposed long ago and continues to be of interest (10). Such proximity effects can also conceivably exist in cis-vinylene sets. According to Charton (lo), the proximity effect can be pictured in terms of three possible major factors: (a) electrical effects; (b) steric effects; (c) intramolecular secondary bonding. As proximity electrical effects are a function of the UI and OR constants, and secondary bonding interactions when present may be a function of the uI constants; the effect of an ortho- or a cis-vinylene substituent may be represented by an equation including electrical and steric terms. The presence or absence of a steric effect may be ascertained in the following manner (72). There are four major cases of interest. (a) The steric effect obeys a linear free energy relationship. Then we may write the equation QX=CWOI,X+@R,X

+

$Vx + h

(24)

where u is the steric parameter. We may define u by the equation

ux

5

rv,x - r V , H = rv,x - 1.20

(25)

where rv,x is the Van der Wads radius of the X group and W,H is the Van der Wads radius of the H atom. Values of ux are reported in Table XI. (b) The steric effect does not obey a linear free energy relationship. Then for any given member of the set, we may write

QX=W,X+POR,X+S[ + h (26) where SX is the steric effect of the substituent. (c) The steric effect is constant. Then Qx = ~

, + @xR , x + ~ ’

(27)

where h‘ = h + Sx. (d) The steric effect is negligible or nonexistent. Then

% =aoI,X ‘@R,X+h

(2)

The data to be examined are correlated with eq. (24). Successful correlation with eq. (24) is a necessary but not sufficient condition for the existence of case (a). Strong evidence for case (a) is provided by a confidence level of J, greater than or equal to 90.0. The confidence level of J, is obtained by means of a “student t” test of J,. If J, is not significant, then this fact implies either the existence of cases (b), (c), or (d), or the use of an incorrect steric parameter. The data are now correlated with eq. (2). If the correlations with

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

99

TABLE XI Values of v

X

U

F NO2 t-Bu H

.27 .35 1.24

0 a

X CI O=C-Za OZ C,H,

u

.55

SO .32 .57

x

Br Ph NZ'Z' S0,Z

u

x

U

.65 .57 .35 .99

I Me SZ Me$

.78 .52 .60 1.40

X CN CH,Z CF,

v

.40 .52 .91

z i s any atom or group of atoms.

eq. (24) and (2) are both unsuccessful, either case (a) exists and the choice of steric parameter is incorrect, or case (b) exists. Although it is impossible to distinguish between these alternatives at the present time, the second is the more likely. If the data give significant correlation with eq: (2), then cases (a) and (b) may be excluded, as in those cases the data must include a variable steric term which is not accounted for by eq. (2). Then a nonsignificant value of $ obtained in a correlation with eq. (24) coupled with a successful correlation with eq. (2) indicates the existence of case (c) or case (d). A comparison of the experimentally observed values of h (that data point for which X = H) with the calculated value of h obtained from the correlation serves to distinguish case (c) from case (d). In case (c), h&s st halowhereas in case (d), hobs = hCde Once again, the data have been divided into three categories: equilibria, rates, and physical properties. 1. Equilibria Ionization constants of cis-3-substituted acrylic acids have been correlated with the Hammett equation by Hogeveen (58) and by Charton (60). Charton has correlated ionization constants for a number of other cis-vinylene sets with the Hammett equation (60). Charton and Charton have correlated some cis-vinylene sets with the extended Hammett equation [eq. (2)] (73). Sufficient data are available for twelve sets of cis-vinylene equilibria, of which four sets represent ionization constants of hydroxy compounds (sets 12-1 to 12-4) and eight sets represent ionization constants of carboxylic acids (sets 12-5 to 12-12). All sets have been correlated with eq. (24) and eq. (2). Sets studied are reported in Table XI. Results of the correlations are reported in Table XIII. Sets designated A were correlated with eq. (24), sets designated B were correlated with eq. (2). In the case of the second ionization constant of 2,3,5,6-tetrahydroxy-l,4benzoquinone (set 12-3), it is uncertain which hydroxyl group ionizes: therefore, the value for X = OH was excluded from the correlation. All of the sets 12-1 to 12-4 gave significant correlations with both eq. (24) and eq. (2),

12-1 12-2 12-3 124 12-5 12-6 12-7 12-8 12-9 12-10 12-11 12-12 12-13 12-14 12-15 12-16

Set

Q

1’

I.

Solvent

I,

a-Substituted tetronic acids H Z 0 3,6-Disubstituted-2,5dihydroxy-l,4-benzoquinones 3,6” 2,5 ” 1,4 3-Substituted-2-hydroxy-1,4-naphthoquinones cis-3-Substituted acrylic acids ,, ” 3 ” 50% v/v EtOH-H,O ” 3 ” methacrylic ” H*O trons-3Chloro-cis-3-substituted acrylic acids p-Substituted trans cinnamic acids p” 50% V/V EtOH-H,O pp” ” crotonic ” H2O cis-3-Substituted acrylic acids MeOH ” 3 ” methylacrylates 70% v/v dioxane-H,O ” 3 ” acrylicacids EtOH ,, ” 3 ” t-BuOH

Substrate

cis-Vinylene Sets

TABLE XI1

”

MeOH OHPh,CN,

25 25 25 26-33 25 25 25 25 25 25 25 25 35 18.8 30 30

Reagent T“C

60 60 60 60 59,60 58 60 60 60,74 50 49 60 69 69 59 59

Ref.

12-17 12-18 12-19 12-20 12-21 12-22 12-23 12-24 12-25 12-26 12-27 12-28 12-29 12-30

d ” ”

3 1

”

”

methylacrylates -1-butene-3-ones

propenes

2-Substituted-l,4-naphthoquinones

” ”

”

’I

1 1

rruns-1 -Substituted-2-bromoethylenes ” 1 ” 2-chloroethylenes ” 2 ” styrenes

1,

,, 3 ” 3 ” methyl acrylates Substituted ethylenes

”

”

a ir spectra frequencies. Parameters for the calculation of chemical shifts in nmr spectra. Chemical shifts. Frequencies, nmr s p e c ~ a .

vd

6 6

6 6 6

6 6

5

va Zb

kr

THF

cc1,

EtOAc ”

”

30 30

80

59 69 54 53 55 56 56 56 56 56 57 56 56

TABLE Results of Correlations ~

Set

12-1A 12-1B 12-2A 12-2B 12-3A 12-3B 12-4A 12-4B 12-5A 12-5B 12-6A 12-6B 12-7A 12-7B 12-8B 12-9A 12-9B 12-10B 12-llA 12-llB 12-12A 12-12B 12-13A 12-13B 12-14A 12-14B 12-15A 12-15B 12-16A 12-16B 12-17A 12-17B 12-18A 12-18B 12-19A 12-19B 12-20A 12-20B 12-21A 12-21B 12-22A 12-22B 12-23A 12-23B

&

-3.51 -3.71 -8.22 -7.83 -8.41 -7.72 -5.67 -3.23 -2.28 -2.41 -1.08 -1.85 -3.75 -1.80 -1.03 -2.12 -2.25 -3.02 -3.23 -3.34 -3.14 -3.14 .0325 -.405 2.81 2.30 1.98 1.90 2.37 2.30 3.30 3.21 30.5 28.2 1.06 1.22 -.775 -1.02 31.7 78.5 -1.14 - 1.26 -1.72 -1.92

P

tL

-2.16 -1.71 -6.37 -6.48 -4.82 -5.04 -3.99 -6.30 -1.71 -1.56 -4.94 -4.62 -5.16 3.11 -3.44 -.929 -.463 -2.13 -3.74 -3.20 -2.67 -2.55 -.403 1.83 1.90 4.53 1.97 2.37 2.41 2.81 3.52 3.98 12.4 24.6 2.14 2.21 -2.86 -2.89 170. 169. -1.65 -1.41 -3.71 -3.38

-.739 .608 1.10 .952 -.274 -.588 -2.01 -.313

-.345 -.0625 -1.43 - 1.68

-.253 -.250 -.295 -7.81 .520 -1.17 73.4 -.476 -.362

102

h

RB

.967 3.93 .960 3.63 .998 2.78 2.82 .997 5.18 .9996 .994 5.26 .9991 4.01 .995 4.12 .987 4.22 .981 4.12 .990 5.42 .983 5.33 .982 4.66 .939 4.54 .960 3.43 .910 4.46 .900 4.39 ,994 5.76 5.55 .998 .992 5.48 4.70 .996 4.69 .996 1.29 .983 1.oo .661 .99996 1.61 1.27 .734 .114 .987 .0621 .976 .988 -.358 - .409 .981 -.648 .992 -.708 .986 1.000 1735. .962 1733. -.0476 .913 .906 .171 ,915 .269 ,850 -.148 .968 311. .905 327. .0762 3 9 5 -.0972 .879 -1.15 .962 -1.25 ,955

Fb

33.28e 46.61e 178.2g 285.2e 4 105.5' 89.21' 381.1f 138.3f 48.40f 64.02e 16.741 29.19' 9.167' 7.4501 5.903' 1.596' 4.284' 40.57' 93.92k 64.16' 82.43f 178.2e 9.435' .777' 3917.' 1.166' 13.04' 20.24j 13.65: 25.0d 19.951 35.94' 143.ak 12.56k 3 1.60e 45.81e 6.903k 6.525' 24.94f 13.64g. 6.677' 10.23' 4.111' 10.2gk

-

XI11 with cis-Vinylene Sets

.198 ,198 ,085

.252 .395 ,631 .154

.085

.163 .163 .786 .786 .385 .385 .493 .493 .800

.639 .281 .275 .295 .520 .431 .819 .241 .297 .760

300

.773 .737 .737 .859 .778 .778 .762 .762 .778 ,778 .778 .778 .778 .778 .778 .778 .778 .7¶8 .778 .778 .214 .214 .215 .215 .014 ,014 .199 .199 ,105 .lo5

.629 .665 .656 .710 .562 .691 .656 .710 .656 .710 .656 .710 .656

.710

,656 .710 .656 .710 .354 .272 .237 .022 .481 .015 .230 .375 .524 .485

.323 ,331 .257 .249 .117 .307 .0717 .145 .lo6 .112 .271 .249 248 .322 .256 .420 ,311 .126 ,0769 .113 .0941 .0784 .148 .424 .00928 .483 .110 .lo7 .130 .117 .149 .136 .556 2.21 .327 .330 .371 .441 13.9 21.5 .272 .265 .320 ,246

.446e .427e .66S9 .489e .313' .637g .884! .9 18' .222e .213e 1.11' .571k 1.59" 1.24" 1.34' 1.51h 1.07" 508m ,247' .354h .251h .209e .474p 1.32' .0298g 1.51" .352m ,333' .417m .364' .480k .423h 1.78' 6.91k .4 17h .399g .613" .697" 31.8" 43.2" .418' .383h .880: .568 103

.791! .718' .426g .397e .263' .670h .838' .864g .396h .401h 1.20m 1.oa' 5.89' 3.15" 2.24" 3.93p ' 2.69" 1.30" .704" .941k ,854k .620' 1.3SP 3.52' .0849j 4.01" 1.oo" .885" 1.19" .968" 1.37" 1.13k 5.09" 18.4" .273e .269e .699h .817h 22.2e 34.49 .67Sk S90k 1.52" l.Olk

.614" ,676" .309" .297k .2 16" ,705' 1.30"

1.01p .189" .22op .363" .022gg .269' .319' .367'

.55se

1.36"

"

.44 1

.695" 24.d s79" .848'

.28Se .149e .253g .241g .117h .302g .071Se .12Se .0992e .061ee .258' .218g .248' .3079 .231j .41gk .263g .126h .076gg .097ge .0939e .065ge .148k .367" .00926g .41gk .109" .0910° .130" .lOlk .149m .117' 1.91e .229* .136" .343" .279O 13.0e 18.4e .262' .1510 .320" .157h

11 11

6 6 5 5 6 6 8 8 5 5 5

5 4 5 5 4 5 5 6 6 5 5 5 5 5 5 5 5 5 5 5 5 23 23 8 8 9 9 9 9 5 5

104

MARVIN CHARTON TABLE

12-24A -1.64 12-24B -1.72 12-25A -.982 12-25B -1.08 12-26A -1.30 12-26B -1.47 12-27B -50.9 12-28A -1.14 12-28B -1.30 12-29B -2.60 12-30A -47.7 12-30B, -65.9 12-30B2 -95.3

-3.57 -3.45 -2.54 -2.38 -2.89 -2.62 -40.5 -1.40 -1.30 .808 -104. -105. -121.

-.200 -.391 -.655

-.339

-46.2

-.968 -1.03 -1.31 -1.46 -.337 -.585 -224. -.624 -.740 -.860 -405. -420. -423.

a Multiple correlation coefficient. F test for significance of regression. Partial correlation coefficients of uI on OR,01 on u Standard errors of the estimate, a,0, J / ,and h.

, q

.9998 .997 .937 .930 .945 .932 .985 .929 .919 .954 .926 .888 .967

900.8i 162.4g 16.80f 25.7Se 19.41e 26.27e 16.89' 8.424' 13.56g 5.082' 12.12g 13.03f 43.59e

on v .

99.9% confidence level (CL). 99.5%CL. 99.0%CL. 98.0%CL. i 97.5% CL. j 95.0%CL. 90.0%CL.

although generally better results were obtained with eq. (2). The value of J/ was not significant in sets 12-1 to 12-3, however, and was barely significant in set 12-4. As values of hobs are in fairly good agreement with values of hCdc,,we may exclude case (c). As cases (a) and (b) are excluded by the success of the correlation with eq. (2), we conclude that case (d) prevails: that is, there is no significant steric effect in these sets, Of sets 12-5 to 12-12, only six were large enough to correlate with eq. (24) [it is necessary to have at least five numbers in a set which is to be correlated with eq. (24)] . Of these six sets (sets 12-5 to 12-7, 12-9, 12-11, 12-12), three gave significant correlation with eq. (24). None of these sets (12-5, 12-11, 12-12) gave significant values of J / .Of the eight sets correlated with eq. (2), four gave significant results. Of the remaining sets, two had only four points [minimal sets for correlation with eq. (2)] and two had five points (sets 12-8, 12-10, 12-6, and 12-9, respectively). No conclusions are possible for those sets which did not correlate with either eq. (24) or eq. (2). In the case of the other sets, we can immediately exclude cases (a) and (b). The

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

105

XIII-cont.

.I74 ,174 ,250 .250 .250 .250 .177 .039 .039 ,773 ,073 ,073 .189

.423 .392 .243 .293 .243

.293

S 1 7 .245

3 6 9 .013

,0207 ,0595 ,224 ,220 250 .260 4.90 .I94 .185 .211 14.6 16.6 9.86

.050gh .135g .344' .318B .384h .374g 10.2m .416k .333h 1.11" 28Sm 29.9k 19Sg

.0870h .234g .498' .453,

.0507m

3 5 9

S14"

s34g 19.6" .437J .397J 1.86O 19Sg 22.1g 13.8e

"

.46 1

,455" 26.7m

.0206h .0375g .215, .123e .239" .145g 5.38h. .192' .108g .192m 13.1e 10.6e 6.33e

5 5 11 11 11 11 4 8 8 4 10 10 9

e 0 . m CL. 80.0% CL. " 50.0%CL. O 2O.O%CL. <2O.O%CL. Number of points in set. Correlation is not significant because of difference in sign between 01 and p. Significance of r is <90% CL unless otherwise noted. Confidence levels for significance of regression are reported as superscripts on F values. Confidence levels for significance of a,p, $, and h are reported as superscripts on values of s,, sp, s$, and sh.

*

values of hobs are in reasonably good agreement with the values of hcdc. We may therefore conclude that these sets (12-5, 12-6, 12-11, 12-12) are examples of case (d). With regard to the composition of the electrical effects, values of pR for the sets studied are reported in Table XIV. The sets in which the hydroxyl group is the reaction site generally exhibit a pR value of about 39. The cis-3-substituted acrylic acids show a pR value of 39 in aqueous solution. The value of 71 obtained in 50% aqueous ethanol seems too large. 2. Reaction Rates Bowden has studied the application of the Hammett equation to the kinetics of the reaction of cis-3-substituted acrylic acids with diphenyldiazom'ethane (59) and with methanol (69) and the rates of alkaline hydrolysis of cis-3-substituted methyl acrylates (69). The sets studied are reported in Table XII. Results of the

MARVIN CHARTON

106

TABLE XIV Composition of the Electrical Effect-cis-Vinylene S Sets Set

pRa

Set

pR

12-11 12-12 12-13 12-14 12-15 12-16 12-17 12-18 12-19 12-20

49 $5

Set

PR

~~~

12-1 12-2 12-3 12-4 12-5 12-6 12-7 12-8 12-9 12-10

32 45 39 66 39

”

55

54

12-21 12-22 53 12-23 64 12-24 67 69 12-25 12-26 12-27 j0 12-28 12-29 12-30 56e

6b4

a Values of pR were obtained from correlations with eq. (2). Correlation was not significant for this set. p was not significant for this set. a was not significant for this set. pR was calculated from set 1 1-30B2.

correlations with eq. (24) and eq. (2) are given in Table XIII. The acid-catalyzed rates of esterification of the cis-3-substituted acrylic acids (set 12-13 ) did not give significant correlation with either eq. (24) or eq. (2). In contrast, the acid-catalyzed esterification of 2-substituted benzoic acids is correlated by eq. (2) with the resonance effect predominant (75). The base-catalyzed hydrolysis of cis-3-substituted methyl acrylates (set 12-14) is correlated by eq. (24) but not by eq. (2), and $ is significant, suggesting the existence of case (a). Again, this behavior is in contrast to that of the 2-substituted methyl and ethyl benzoates, which correlate best with eq. (2) and show a predominance of the localized effect (76). As sets 12-13 and 12-14 are small, it would be useful to reinvestigate these reactions with more extensive data and in other solvents. The three sets of rate data for the reaction of cis-3-substituted acrylic acids with diphenyldiazomethane all give significant correlations with eq. (2) but not with eq. (24). This fact excludes cases (a) and (b). As the values of hcdc and hobs are not significantly different, the data must belong to case (d): that is, there is no meaningful steric effect. 3. Physical Properties Chemical shifts of cis protons in substituted ethylenes and in trans-1,2disubstituted ethylenes have been correlated with the Hammett equation in

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 107

several instances (77-79, 54). Crecely, Crecely, and Goldstein (80) have correlated chemical shifts of cis protons in 2-substituted naphthoquinones with the up constants. Data for twelve sets of nmr chemical shifts of cis protons are extant. The sets studied are given in Table XII; results of the correlations with eq. (24) and eq. (2) are set forth in Table XIII. Eight of the ten sets correlated with eq. (24) gave significant results. Of the 12 sets correlated with eq. (2), 10 gave significant results. The ten sets which did not give significant results with eq. (2) had only four members each. It must be noted that best results for correlation of set 12-30 with eq. (2) are obtained by the exclusion of the value for X = OAc (set 12-30B2 in Table XIII). In general, better correlation was obtained with eq. (2) than with eq. (24). Of the eight sets which gave significant correlation with eq. (24), seven did not have meaningful values of $ . It would seem then that we can exclude cases (a) and (b). The values of hcdc are not significantly different from the values of hobs : therefore, case (c) may be excluded, and the data generally belong to case (d). That is, there is no steric effect. The composition of the electrical effect in the case of nmr chemical shifts for substituted ethylenes is indicated by the value of pR of 53 for set 12-22. The results for sets 12-20 and 12-21 suggest, however, that this value may be too low (a was not significant for these sets). The composition of the electrical effect in the case of the trans-1,Zdisubstituted ethylenes bearing a constant substituent will depend on whether or not their 01 and 0 values obey eqs.(21) and (22). Niwa (56) has suggested that in correlations of these data with the Hammett equation, the p values obtained obey eq. (20). Correlation of 01 with eq. (21) did not give significant results, whereas correlations of 0 with eq. (22) did give significant results. The rrans-l,2-disubstituted ethylenes show an average p~ value of 62. The values of p~ for the sets studied are set forth in Table XIV. The carbonyl stretching frequencies in the ir spectra of cis-3-substituted methyl acrylates (set 12-18) were also correlated with eq. (24) and eq. (2). Barely significant correlations were obtained with both equations. The value of I ) obtained in the correlation with eq.(24) was not significant. We may therefore probably exclude cases (a) and (b). As the hcdc is not significantly different from hobs, we may exclude case (c). This set is therefore probably an example of case (d): that is, there is no meaningful steric effect. No conclusion can be made with regard to the composition of the electrical effect in this set, as 0 was not significant in the correlation with eq. (2). In conclusion, it would seem that most sets of cis-vinylene data are free of steric effects.

E. Reactions of Carbon-Carbon Double Bonds Among the most important reactions of olefinic compounds are those involving the carbon-carbon double bond. It is convenient to divide phenomena occurring

108

MARVIN CHARTON

at carbon-carbon double bonds into formation of charge transfer complexes and addition reactions. 1. Charge Transfer Complexes

The ability of compounds with double bonds to act both as electron donors and as electron acceptors in charge transfer complex formation is well known (81, 82). Hammond (83) has studied the correlations of association constants and of the energy of the charge transfer absorption of 2-substituted-l,4benzoquinones complexed with hexamethylbenzene with the Hammett equation. Charton (84) has studied the correlation with eq. (2) of association constants of 1-substituted propenes with Ag' . Sufficient data are extant for three sets of charge transfer complex association constants and one set of charge transfer absorption energies. The sets studied are reported in Table XV. Results of the correlations with eq. (2) are given in Table XVI. All the sets studied gave significant results. An improvement in the correlation for set 15-2 occurs on the exclusion of the values for X = Ac and X = C 0 2Me (set 15-2BA). The composition of the electrical effect in the case of the 1,4-benzoquinones seems to depend upon the degree of substitution. The association constants and charge transfer absorption energies of the 2-substituted-l,4-benzoquinone-hexamethylbenzene complexes (sets 15-2 and 15-4) show values of pR of 55 and 44 respectively. Values of pR are set forth in Table XVII. 2. Addition Reactions Perhaps the most characteristic property of the carbon-carbon double bond is its ability readily t o undergo addition reactions with a wide range of reagent types. It will be useful to consider addition reactions in terms of several categories: (a) electrophilic additions; (b) nucleophilic additions; (c) radical additions; (d) carbene additions; (e) Diels-Alder cycloadditions and (f) 1,3-dipolar additions. a. Electrophilic addition. The correlation of rates of addition of chlorine to 3,3-disubstituted acrylic acids with the Hammett equation using the constants was reported by de la Mare (86). Dubois and co-workers have correlated rates of bromination of substituted ethylenes and multiply substituted ethylenes with the Taft modification of the Hammett equation (87,88, 89, 90). Dubois and Bienvenue-Goetz (90) have also considered the use of the equation

ui

Q x = p * C ~ z+6Z&,x + h

where the

(28)

& values are the steric parameters of Taft. Dubois and co-workers

5:

,,

H2O

aq. HCIO, CF,CO,H H2O

,,

AcOH AcOH MeOH AcOH, HBr

15-21 15-22 15-23 15-24

rruns-2'-Substituted styrenes 2-Substituted propenes , " 2 Substituted ethylenes

'?

?runs-l,2-Disubstituted elthylenes " 1,2 Substituted ethylenes trans-2'-Substituted styrenes Substituted ethylenes

trun~-2'-Substitutedstyrenes Substituted ethylenes

4-benzoquinones 2-Substituted- 1,4-benzoquinones Substituted ethylenes AcOH AcOH-H~O AcOH aq. HCIO,

H*0 cc1,

1-Substituted propenes " -1,4-benzoquinones 2-

2,3,5,6-Tetrasubstituted-l,

Solvent

Substrate

THF

Q

15-20

15-4 15-5 15-6 15-7 15-8 15-9 15-10 15-11 15-12 15-13 15-14 15-15 15-16 15-17 15-18 15-19

15-1 15-2 15-3

Set

CarbonCarbon Double-Bond Sets

TABLE XV

diglycine anion glycine anion c-aminocaproic acid anion DL-alanine anion

Reagent

Ref.

0

108 108 108 108

100

24 25 25 25 25 24 24 25 24 24 38 25 25

30 30 30 30

83 94 95 94 96 96 96 96 94 94 87,91 94 94 97 98 99

25 24

25 84 25 83 18-20 85,83

T"C

+.

15-25 15-26 15-27 15-28 15-29 15-30 15-31 15-32 15-33 15-34 15-35 15-36 15-37 15-38 15-39 1540 1541 1542 1543 1544 1545 1546 1547 1548 1549 15-50 15-51 15-52 15-53 15-54 15-55 15-56

Set

Q

1-Substituted-2-methylpropenes 1 ” 2 2 ” propenes

2-Substituted propenes Substituted ethylenes

nuns-1,2-Disubstituted ethylenes ” 1,l” ” Substituted ethylenes

Substituted ethylenes

1,l-Disubstituted ethylenes

” propenes 2 Substituted ethylenes

Substrate

I9

0

THF

.,

3,

,,

,,

,,

9,

9.

,.

,,

9,

,I

9.

gas phase

isooctane

isooctane gas phase

,,

9,

vinyl acetate radical methyl methacrylate radical methyl acrylate radical dichlorocarbene

Cl,H*, so styrene radical

9.

Br,

F,No

Pho

CCl, cyclopropyl radical

CFO,

CFO,

Eta

0 -78 -78

60

60 60 60 60

78 100 118 40 80 120

65 65

138 139 139 139 139 139 140 140 140

137

Meo

isooctane

,, ,,

110 109 109 109 111,123,124 111,123,124 125 126 130 130 131 131 132 133 133 134 135,136 135,136 135,136 137 137 137

24 0 30 45 65 65 60 100 65 180 65 65

OMeMorpholine

MeOH

gas phase

Ref.

T“C

Reagent

Solvent

Table XV-(continued)

c.

15-57 15-58 15-59 15-60 15-61 15-62 15-63 15-64 15-65 15-66 15-67 15-68 15-69 15-70 15-71 15-72 15-73 15-74 15-75 15-76 15-77 15-78 15-79 15-80 15-81 15-82 15-83 15-84 15-85 15-86 15-87 15-88 15-89 15-90 15-91 15-92 ”

trans-l,2-Disubstituted ethylenes ” 1,2

trans-3-Substituted alkyl acrylates 2-Substituted alkyl acrylates Substituted ehtylenes

trans-3-Substituted ethyl acrylates Substituted ethylenes

”

1,3-butadienes ” 1,3 ” 1 ” 1,3 ” 2,3 ” 1,3 ” 2,3 ” 1,3 ” 2 ” 1,3 ” 2‘ ” 1,3 ” 2 ” 1,3 ” 2 ” 1,3 ” trans-l,2-Disubstituted ethylenes cis 1,2 trans 1,2 cis 1,2 trans 1,2 cis 1,2 trans-3-Substituted methyl acrylates ” 3 ” acrylonitriles ” 1,2-Disubstituted ethylenes cis 1,2 ” 1,l Substituted ethylenes

2 2 2,3

Me, NCHO PhMe

CHCl, Et, 0 PhH

CCI,

Dioxane

PhH

,I

THF PhH, AlCI, ,,

>,.

dioxane

PhH

,

91

diphenyldiazomethane N-methyl€-phenylnitrone

picryl azide benzonitrile oxide diphenylnitrile imine

I.

phenyl azide

9,l Odimethylanthracene cinnamaldehyde isoprene pentachlorocyclopentadiene

2,3dimethylbutadiene

9,lO dimethylanthracene

cyclopentadiene

te tracyanoethylene methyl acrylate

maleic anhydride

80 80 80 40 120 85 120

20

25 25 25

-18 25 25 30 30 roomT 20 20 20 20 40 40 20 20 130 130 130 130 130 130 130 170

140 142 142 142 142 142 143 143 143 143 142 142 142 142 142 142 142 142 142 142 142 142 142 144 144 146 147 148 146 146,148 149 149 150 151 151 151

-3.60 1.23 1.15 2.27 -.693 -9.72 -13.5 -7.14 -6.22 -22.4 -19.1 -10.7 -8.35 -13.0 -9.76 .328 -7.49 -3.72 -4.32 -8.48 -18.3 -1.26 1.79 1.90

15-1 15-2B1 15-2B2 15-3 15-4 15-5 15-6 15-7B, 15-7B2 15-8 ,Y 15-9 h, 15-10 15-11 15-12 15-13 15-14 15-15 15-16 15-17 15-18 15-19 15-20 15-21A 15-218 15-21C 15-22A 15-22B

1.70 ,995

a

Set

-5.21 .942 1.39 -.310 -.540 -5.60 -3.38 -3.02 -4.77 2.29 332 -5.82 -2.73 -3.56 -4.53 -13.2 2.20 6.80 -32.9 -13.7 -.554 -3.88 19.2 4.31 23.5 19.4 8.14

P .794 -.266 -.0952 -.244 -.540 2.28 .912 3.41 2.94 6.10 4.86 4.70 3.32 2.25 2.37 1.64 1.93 2.01 -.158 ,672 .835 .444 -1.45 -1.17 -1.09 -.940 -1.58

h

.987 .862 .96 1 .986 2.98 .980 .965 .881 .928 .974 .964 .857 .837 .981 .931 .973 .990 -990 .959 .985 .995 .948 .797 .678 .699 .921 348

Ra

8.437k 2.568'

38.93' 11.58' 36.67e 35.07' .971 49.28' 40.82e, 8.672' 12.45: 28.15: 19.98' 2.762l 2.337' 78.65e 3.238' 44.79e 48.46i 48.64i 22.96' 16.46l 262.7e 22.04' .873' ,424'

Fb

.376 ,193

.976' .028 .094 .778 .215 .244 .378 .012 .121 .838k .838k .376 .376 .133 .178 .477 .330 .512 .447 379 .694 ,428 ,319 .418

rc

.286 ,236 .146 .144 .0665 .369 .696 .756 .603 .974 1.01 1.94 1.43 .440 1.09 .569 .228 .187 .65 1 ,375 .187 ,192 ,758 .924 .635 .495 .773

d Sest

d

Sff

1.61" 2.49'

3.18" .33gg .21lr: .449J .0882e 1.35' 1.5Se 1.79h 1.50h 5.231 5.43J 6.85" 5.05" 1.04e 3.93" 1.3SP .895h .423h 3.46" 1.8grn 1.12e .492k 2.81' 3.58O

Results of Correlations with CarbonCarbon Double-Bond Sets

TABLE XVI

6.41' .311h .230e .120p .066 le 1.15' 3.71" 2.39" 2.1Ok 10.5p 10.9p 5.54" 4.08O 1.75k 4.63O 1.61e 1.03rn .81fjh 6.08' 2.41rn 1.93O .875' 2.14' 9.33O 17.0". 4.76' 3.59rn

1.05" 1.98O

.124m .0367e .60 1 .397" .7819 .667h .886' .920h 3.33" 2.45" .23ge 1.15" .292' .239h ,201' .587p .375" ,1749 .0990g 2.14O 3.15O

.loo"

.143rn

d Sh

5

4 4 4 6

8 5 5 7 4 8 8

5 5 9 4

7 6 6

9 8

5 11 9 5 11 7

nq

15-22C 15-23A 15-23B 15-23C 15-24A 15-24B 15-24C 15-25A4, 15-25A2 15-25B 15-25C1 15-25C2 15-26Al 15-26A2 15-26B 15-26Cl 15-26C2 15-27A, 15-27A2 15-27B 15-27C1 15-27C2 15-28A, 15-28A2 15-28B 15-28C1 15-28C2 15-29-1 15-29-2 15-30-1 15-30-2 15-31-1

.923 1.93 3.13 3.05 2.54

-1.95 ,817 -.434

-1.30 2.33 1.71

-1.74 2.30 2.21

-1.39 2.27 .895

2.25 2.71

2.38 2.54

17.5 17.8 3.63 23.6 20.2 9.26 17.1 8.76 18.1 7.53 10.1 14.4 19.9 35.0 7.94 22.0 31.6 19.4 32.9 7.13 20.8 29.6 14.7 25.1 5.77 16.9 23.9 3.16 3.32 .699 1.05 2.44 ,0124

-2.13 .831 - 2.6 2 -1.49 .138 -1.26 2.08 -.554 .365 1.04 -.0758 2.30 1.79 1.66 1.66 1.08

-.555

-.140 -.0337 -1.45 -2.81 -.211 -.0538 -3.13 -3.35 -.804 -1.62 .375 -3.47 -2.60

-.5 14

.891 ,794 .698 .643 ,911 .865 ,877 .654 .976 .951 .610 .918 599 374 ,882 .590 .862 .628 .892 .877 .622 ,877 ,689 .944 .918 .667 .941 .751 .944 .956 .954 .755 3.870k 16.44' 10.49k 5.074' 3.969k

2.718' 20.52f 5.345'

1.9571 9.699' 3.337'

1.401' 6.489k 3.505'

.746' 9.869' 5.431'

4.862' 1.49 1'

.855' ,476'

.205 .173 .786 324 .208

,435 .528 ,280

.435 .528 .280

.453 ,540 .280

,327 S82 .426

.538 .465

,319 ,418

,501 ,834 .983 .744 .632 1.02 .60 1 .934 ,340 .450 .799 .435 1.76 1.09 1.14 1.62 1.02 1.42 .841 1.06 1.33 .820 1.oo ,464 .707 .957 .435 .725 .408 .384 .541 .768 1.26" .757k 1.18m 1.85" 1.36m .

3.28' 1.62' 2.97p

4.64' 2.95" 4.43'

5.80° 3.85' 4.80'

3.16' 1.51" 1.83'

2.66" 4.63'

3.10' 3.80'

.448h 23.5' 9.93' 1.99" 6.16k 5.41" 5.42k 9.39" 4.23m 2.38m 7.59" 4.39k 15.0: 10.6J 3.02m 12.3m 8.30h 11.8m 8.04' 2.78m 9.90k 6.61g 8.33m 4.41g 1.86k 7.14' 3.50e 1.28' .720g 3.02m 5.52p 1.46m .396g .260g .307J .433m .44 1

1.98" 1.07' 1.6lP

2.81' 1.95" 2.41'

3SIp 2.53" 2.6 I"

2.06p 1.11" 1.57"

1.63" 3.35'

2.35p 3.36*

4 9

5

9 8 9 7

5

9 8 9 8

5

8 7 9 8

5

4 8 7

5

4 4

5 5

4

5

6 4 4 4

15-31-2 15-32-1 15-32-2 15-33-1 15-33-2 15-34-1 15-34-2 15-35-1 15-35-2 15-36-1 15-36-2 15-37-1 e 'i; 15-37-2 15-38 15-39 15-40 1541 1542 1543 15-44-1 15-44-2 15-45-1 1545-2 1546-1 1546-2 1547-1 15-47-2 1548-1 15-48-2

Set

-.0898 2.11 1.35 .0727 -1.93 -1.70 -1.06 -2.47 -5.00 -2.28 -4.44 -1.41 -3.47 -4.79 -12.1 -.128 -.487

-.850

3.13 1.42 2.43 -.470 -.282 -.173 -.0570 -1.19 -1.35 -1.53 -1.72

3 '

2.5 1 1.96 1.43 2.58 2.04 1.93 1.73 .701 -.0338 .783 -.799 -8.18 -3.39 3.07 2.33 .212 -5.78 -4.93 -4.55 2.19 -8.26 1.98 -6.92 2.43 -4.94 4.71 -25.4 -.929 -1.52

P .782 1.80 1.19 2.44 2.05 1.78 1.60 2.47 2.20 2.4 1 2.09 -.411 -.5 13 1.35 1.37 1.08 ,916 1.51 1.91 .950 .0506 .820 .0530 .564 .0256 2.61 .0129 .0578 -.153

h

.872 .694 352 .783 .943 .El4 .938 324 343 350 .877 .483 .827 .953 .998 .086 .990 .992 .997 .86 1 .975 373 .968 367 .957 .I75 .999 .352 393

Ra

47.93: 63.06' ?178.4g 4.289' 19.08' 4.798' 14.73k 3.020' 5.448' 2.251' 480.0f .4961 9.884'

.015'

7.968J .929' 1.322' 2.382k 4.042' 1.966' 3.638' 3.163' 2.461' 3.897' 3.347l .759l 3.240' 14.98' 103.1k

Fb rc

.194 .228 .304 .876k 363' 371 363 .727 .714 ,727 .714 .133 .080 .758 .916 .484 346 .846 346 .82tik 346 .828k 346 .823 .859 .828k 346 .083 .312

Table XVI-(continued)

.603 .975 .912 .528 .290 .382 .228 .396 .372 .444 .402 .906 .161 .122 .120 .429 .0621 .0466 .0263 .765 .259 .664 .269 ,626 .304 2.12 .115 SO8 .161

d

Sest

d

1.18 2.03O 2.09" 2.00' 1.10' 1.45' 364' .904" 360" 1.01" .931" 2.57O .46lP .406h .462" 1.13p .21.Sh .16lg .0909g 2.16". 396' 1.21". .92$ 1.98' 1.22" 6.00" .397g 1.19p .444"

sff

1.1Sk 2.01" 1.94' 3.06" 1.69" 2.22" 1.33" 1.36O 1.42' 1.53O 1.54p 7.23" 1.35k 1.09 .791" 1.96' .598h .449g .253g 3.86O 2.5Ok .59l0 2.59m 3.24O 3.12" 10.7O 1.1og .933" .342g

spd

.371k .826m .949" .346g .231k .272' .181k .326g .382' .366g .4 13' 3110 .144' .120g .120; .416 .0615g .046 1 .0260e .531m .257p 1.7fim .266' .475" .303' 1.47m .114p .268' .0896m

d Sh

4 6 5 10 8

5

6 5 6 5

5 5 5

8 6 6 4 7

5

6

5

4 6

5

4 6 4

5

8

nq

vI

E

15-49-1 15-49-2 15-50 15-51-1 15-51-2 15-52-1 15-52-2 15-53-1 15-53-2 15-54 15-55 15-56 15-57 15-58 15-59 15-60 15-61 15-62 15-63-1 15-63-2 16-64-1 15-64-2 15-65-1 1565-2 15-66-1 15-66-2 15-67 1568 15-69 15-70 15-71 15-72- 1

.432 2.86 1.78 ,222 3.18 -.485 2.80 -5.86 -.803 -4.91 -4.67 -3.31 -3.73 -4.75 -4.12 -4.08 -2.96 -8.91 -3.88 -2.94 -3.62 -2.90 -2.05 .5 14 -.865 -.284 2.58 2.46 2.08 2.66 1.70 3.73

3.40 3.48 11.3 3.05 2.46 .736 2.18 .809 .55 1 -4.23 -3.91 -3.96 -4.73 -4.02 -3.85 -4.25 -1.65 -13.3 -2.02 -1.80 2.58 2.75 2.71 2.88 4.27 4.40 8.07 .905 12.6 1.98 5.90 -6.56 1.48 .47 1 .673 4.56 3.18 2.04 .587 q SO6 3.07 -.132 -.lo7 -.857 -1.04 -.534 -.811 -4.30 -4.16 -1.28 1.54 .990 ,713 .292 1.20 .783 .966 .626 -6.13 -5.62 -7.11 -6.54 -4.82 -4.78 .680 .995 .640 .895 .129 .915 ,766 .437 .993 .995 .825 .799 .939 .989 .980 .99999 .975 .906 .9997 .900 .995 .675 .996 .852 .981 .925 .871 .981 ,894 .859 .793

355

3.019: 6.8 14' 53.39k 1.385' 6.043k .034' 5.148' 2.842' .236' 37.48' 50.22k 1.068' .885' 14.90' 87.3Ie 12.4 1' 20408: 9.598' 4.581' 928.5' 4.287' 50.23k .839' 71.02k 2.640' 12.801 20.77' 6.270k 52.3If 5.991k 9.824' 2.548' .062 .821 .198 .262 .lo3 .017 .130 .04 1 .556 .556 .854 .854 .617 .659 .869 .384 .636 .381 .330 .381 .330 .381 .330 .381 .330 .090 .303 .303 .271. .747' ,791

.loo .842 .662 .197 .948 .540 1.10 .378 .968 .487 .205 .167 .739 .992 .347 .219 .197 .00625 .835 .781 ,0387 .609 .136 .603 .0803 .5 16 .248 .523 .543 .3 75 .617 .764 .946 .964" 2.26p 1.61m 2.21p .95Sk 2.56k 1.88' S91k .482k 6.25' 8.39O .873g .321e 1.74" .0148' 2.07m 1.59m ,085 lh 1.24k .299k 1.22p .177" 1.05" .545' .679g .76d .524h .863k 1.24" 1.81m

1.68p 1.64m 2.62m 1 .90m l.lom 4.59p 1.60" 2.11' 1.06' .638k S21k 3.41" 4.58: 1.08' .633' l.Olrn .0340h 6.38" 2.81' .14d 2.19" .490m 2.17" .289k 1.86m .894m 1.66g 2.35' 1.62g 2.91' 3.33m 6.10"

1.4 1; 1.11' 2.60" .90lg .682h .862k .392" .792g .669 .157' .128' ,479" .642" .20Sk .16Og .14d .00520e 1.39' .658m .0378' S13" .133" .508m .0785k .43sm .242" .620e .66Sg .459e .769g .596e .844h

S68j .602"

4 5 4 10 7 7 6 10 6

5

4

5

7 5 4 4 4 4 7 7 4 4 4 5 4

5

4 7 6 7

10 8

+,

h

-4.14 -3.59 -3.25 -8.75 -.189 -4.19 -2.70 .352 -.0854 -.206 .307 -.00766 -.234 .957 .958 .652 - ,464 .873 1.68 I .44 1.36 .312 1.26

R

1.32 11.5 12.0 16.5 -1.84 5.89 - 1.43 -.768 1.19 -.993 -1.02 -.724 1.04 14.2 -8.08 ,604 2.43 2.10 3.03 12.3 7.49 4.6 1 4.44

ff

2.03 .643 1.21 2.12 1.20 1.46 -1.32 .226 .708 -.201 - 1.36 -1.51 1.14 -4.63 -2.04 3.28 5.24 3.84 1.71 ,393 1.03 ,979 ,958

a For footnotes, see Table XIII.

15-72-2 15-73 15-74 15-75 15-76 15-77 15-78 15-79-1 15-79-2 15-80-1 15-80-2 15-81 15-82 15-83 15-84 15-85 15-86 15-87 15-88 15-89 15-90 15-91 15-92

Set

.976 .963 .968 .993 ,996 .998 ,999 .537 .9 19 SO3 ,945 .902 .696 .999 .977 .998 .946 398 .9994 .9991 .972 ,995 .996

Ra 20.22' 12.77k 7.385' 37.94' 70.09f 290.Sf 427.2f ,812' 6.181k .679' 12.47' 6.531k .938' 236.1' 31.23g 115.5k, 17.13' 4.164' 4 19.6:' 27 1.5' 34.72' 45.53' 67.16k

Fb

.402 .118 .0666 .099 .275 .785 .385 .06 1 ,128 .162 .817 .775. 374' .307 .307

.417

.846 .786 .824 .851 .85 1 .573 .290

rc

Table XVI-(continued)

.315 ,522 .681 .167 ,0666 .0593 .0303 .131 .0576 ,304 0.124 .221 .654 .0820 .362 ,066 .34 1 ,772 .014 .lo7 .283 .154 .I23

s:st

d

.689k 1.61° 2.33O .670m .267m .187h .129g .3070 .177' .5580 .339' .453J 1.14O .441k ,963m .223j 1.06g 2.61" , .0594j .490° 1.11" .259m .206m

sff

2.56O 4.10" 6.94" 2.37k ,945" .4 14' .0490g .613" .539m .938" .381k .682" 1.04". .708' 1.03g .129m .65 1' .952m .142! .869' 2.33' .642k .511k

d

sl3

.30Sg .416h .54sm 1.21k .483O .0732e .031Se .llSJ .117O .241" .148m .204p .517O. .0736' .221'. .0539' .203k .492" .013lg .152k .281g .A93" .154k

d Sh

4 6 4 7 5 4 4 7 4 4

5

5 7 6 7 6 6

5

5 4 4 4

5

nq

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

117

TABLE XVII Composition of the Electrical Effect-CarbonCarbon Double-Bond Sets

15-1 15-2B2 15-3 15-4 15-5 15-6 15-7 15-8 15-9 15-10 15-11 15-12 15-13 15-14 15-15 15-16 15-17 15-18 15-19 a 01

a

5b5 44

3b7 43 a

a C

C

21 C

d b C

d C

b

15-20 15-21 15-22 15-23 15-24 15-25 15-26 15-27 15-28 15-29 15-30 15-31 15-32 15-33 15-34 15-35 15-36 15-37 15-38

76 C

looe C

looe 1 0oe 1 0oe 1 0oe 1 0oe 63 C

45 C C

C C C

C

59

15-39 15-40 15-41 15-42 15-43 1544 15-45 15-46 15-47 15-48 15-49 15-50 15-51 15-52 15-53 15-54 15-55 15-56 15-57

f C

75 74 73

6b2 C

6d8 b f f C

C C

46 C C

15-58 15-59 15-60 15-61 15-62 15-63 15-64 15-65 15-66 15-67 15-68 15-69 15-70 15-71 15-72 15-73 15-74 15-75 15-76

46 48 C

36 C

38 49 85 C

76 27 86 43 78 39 95

15-77 15-78 15-791 15-80 15-81 15-82 15-83 15-84 15-85 15-86 15-87 15-88 15-89 15-90 15-91 15-92

80 52 63 43 32

32

6d4

C C

C

is a function of OR for this set.

p is not significant for this set. Correlation is not significant for this set. is not significant for this set. Best correlated by eq. (41). 01 and p are not significant for this set. (Y

(91) have reported a correlation of values of AAGJ with the u$ constants. The AAG$ were obtained from

A A G ~= A A G t~AAG; ~

(29) where AAGz0 is the polar contribution and AAG$ the resonance contribution to the free energy. The A A G L term is calculated from the correlation of log k for the olefins whose substituents do not conjugate with the double bond. Charton (92) has examined the correlation of data for electrophilic addition to the double bond with the extended Hammett equation [eq. ( 2 ) ] . For multiply substituted sets, eq. (30) was used. This equation neglects interaction terms (98).

& = a%l,X

(30) +h Sufficient data are extant in the literature t o permit the examination of 15 sets. The sets studied are given in Table XV. The data were correlated with +flxuR,X

118

MARVIN CHARTON

eq. (2) or, where appropriate, with eq. (30). Results of the correlations are set forth in Table XVI. Slightly improved results for set 15-7 were obtained by the exclusion of the value for X = Bz. Of the 15 sets studied, 10 gave significant correlations with eq. (2) or eq. (30). Two of the five sets which did not give significant correlation had only four points, and the remaining three sets had only five points. It seems quite likely that if more points were available, significant correlation would also have been obtained for these sets. With regard to the composition of the electrical effect, examination of the p~ values reported in Table XVII shows that in six of the sets which gave significant correlation, the localized effect is predominant (in these sets, either PR < 50 or 0 is not significant). Thus it would appear that in so far as substituent effects are concerned, there are two major classes of electrophilic addition to the carbon-carbon double bond: predominance of the localized effect or predominance of the delocalized effect. This behavior may well be accounted for in terms of the reaction mechanism. The rate-determining step in the electrophilic addition reaction is believed to be the formation of an intermediate which may be either bridged or a free carbonium ion. X

X \

l

Z Y + c=c

\

X

X ZYi

l

c-c + Y e

--*

\ I

I

c=c

\

-+

‘C-l/+YQ I

\

2

4

or

I

\

I I \ Z 5

Those sets for which the resonance effect is predominant are the sets which are most likely to give rise to the free carbonium ion 5, as the substituents in these sets (sets 15-14 and 15-1 7 and possibly 15-18) are all donors by resonance, as is shown by their UR values. Those sets for which the localized effect is predominant may be accounted for in terms of intermediates 3 or 4. Sets 15-5, 15-7B2,and 15-12 gave significant values of 0. It is difficult to account for this fact in terms of intermediate 4. The results can be accounted for in terms of intermediate 3, however, if this species resembles other three-membered rings, such as cyclopropane, in its behavior. Sets 15-6, 15-8, 15-9, 15-12, and 15-15 include both donor and acceptor substituents. The successful correlation of

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 119

these sets implies that the same mechanism operates throughout the set. It would seem, then, that the formation of free carbonium ions in these sets may be excluded, as those members of the set bearing donor substituents would give 5, while those members of the set bearing acceptor substituents would give 4. As substituent effects are not the same in 4 as in 5, there would result a lack of correlation with eqs. (2) or (30). We may conclude, then, that in these sets, the addition probably proceeds via the formation of the bridged intermediate 3. As all of the substituents in set 15-19 are donors by resonance, with the exception of X = H, if a free carbonium ion were to form, it would be expected to be 5. This intermediate should show a large and significant /3 value. It would seem, therefore, that in set 15-19, the reaction again proceeds by way of the bridged intermediate 3. We have also examined the effect of substituents on orientation in the addition of BH3 to the carbon-carbon double bond. Consider the substituted ethylene XCH=CH2. The boron may become bonded either to carbon 1 or to carbon 2. The overall rate constant for the reaction is given by

where

In eq. (32), p1 and pz denote the percent of the product containing boron at C' and C 2 , respectively. Applying the extended Hammett equation to the partial rate constants kl and kz for the compound bearing the X substituent gives logk1,X =logPl,XkT,X =alul,X 'PluR,X

thl

1% k2,x = 1% P2,XkT,X = a201,x +02UR,X +h2

(33)

(34)

Subtracting eq. (34) from eq. (33) results in

or PlX log __ = atuI,X + ? h , X + h l P2x equivalent to eq. (2). The results of correlation with eq. 36 are excellent (Table XVI). It would seem that orientation in electrophilic addition can be successfully represented by the extended Hammett equation. The results obtained seem to show that orientation in the addition of 'BH3 to olefins is primarily a function of the delocalized electrical effect. The results obtained are surprising in one respect. For that member of the set for which X = H , C'is

120

MARVIN CHARTON

equivalent to C2, and therefore p l = pz = 50. Then h' should equal zero. The value actually obtained is significantly different from zero. We cannot explain this anomaly at the present time. Ledaal and co-workers (101-105) have proposed a linear free energy relationship for predicting the percent zwitterion formed at the ith carbon atom in substituted quinones, substituted dibenzoylethylenes, and substituted acetylenes. Fliszar and Granger (106) have proposed the equation AGJ,p)/2.3 RT

(37)

for the calculation of product composition, where f is the fraction of the cleavage following path a and 1 - - f the fraction of the cleavage following path b. Values of A G i calculated for various groups are reported. The A G i values for CH2Z substituents are linear in the corresponding Taft u* values. There is no overall dependence of AGxt on uI and uR, however. Vrbaski and Cvetanovid (107) have found linear relationships between the logarithm of the rate constant for the reaction of various alkenes with electrophiles and the corresponding ionization potential. b. Nucleophilic addition. The first attempt to apply a linear free energy relationship to the reactivity of substituted ethylenes undergoing nucleophilic addition is that of Friedman and Wall (108). These authors proposed the equation log kx = Pv

+ log I
(3 8)

where kx represents the rate constant for the reaction of the substituted ethylene bearing the X substituent with the anion of some amino acid, kCN represents the rate constant for the reaction of acrylonitrile with the same nucleophile, and PV is a measure of the electrical effect of X relative to that of the cyano group. These authors also reported nearly linear plots of log kx against u - u0 and against UR. A plot of log kx against u-- uo was said to give only qualitative correlation. Shenhav, Rappoport, and Patai (109) have reported a correlation of the rate constants for the addition of morpholine to substituted ethylenes with the PV values of Friedman and Wall. They also report a correlation of the rates with the UR values with p=48. This correlation was limited to substituents with UR in the range .lo-.15. Sufficient data are extant in the literature for eight sets of nucleophilic addition to substituted ethylenes. The sets studied are reported in Table XV. The data were correlated with eq. (2) and with the equation where

Qx = CwUI,X+ PJR,x+h

(39)

G,x= q , x- q x

(40)

u g , ~is defined by

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

121

The u i values reported in the review of Ritchie and Sager (8) were used. The data have also been correlated with the equation

The results of the correlations are given in Table XVI. Sets labeled A, B, and C are the correlations with eqs. (2), (39), and (41), respectively. The results for set 15-25 are improved by the exclusion of the value for X = EtCO, probably because of uncertainty in the UR value of the propionyl group. The results for sets 15-26 through 15-28 are all greatly improved by the exclusion of the value for X = CHO, most likely because of the uncertainty in the value of uR for the formyl group. Best results were obtained for correlations with eq. (41). Of the eight sets studied, six gave significant correlations with eq. (41). The two sets which did not give significant correlation with UR had only four points each and encompassed a range of only .05 u units. Obviously, the electrical effect in nucleophilic addition to the double bond is almost purely a resonance effect. In magnitude, the electrical effect is very large. The values of p obtained range from 14 to 32. This range is comparable to the range of P observed for those electrophilic addition sets for which /? was predominant, the range in that case being -13 to -33. c. Radical Addition. Herk, Stephani, and Szwarc (1 11) have discussed the rates of addition of methyl radical to substituted ethylenes bearing electron acceptor substituents in terms of the u; constants of the substituents. Abell (122) has made an attempt to correlate relative equilibrium constants for the reaction of bromine atoms with substituted ethylenes with the up constants. Price and Alfrey (1 13) have proposed a linear free energy relationship for the calculation of copolymerization reactivity ratios. Their equation is kiz = Pi Qz exp(-eiez)

(42)

where P is considered to be a function of the reactivity of the radical, Q is a function of the reactivity of the monomer, and both P and Q are composed of resonance and steric effects in the monomer. The quantity e is thought to be a polar term characteristic of both the monomer and the radical. The reactivity ratio r, is then given by kii

-

Qi

rl = - - - exp[el(ez -el)] kiz Qz

(43)

where the subscripts 1 and 2 refer to the radical derived from monomer 1 and monomers 1 and 2. Thus k l l represents the rate constant for the reaction of radical derived from monomer 1 with monomer 1 , whereas klz represents the reaction of radical derived from monomer 1 with monomer 2. The reference monomer chosen for the Price-Alfrey treatment was styrene, for which Q and e were originally defined as 1 .O and -1 .O respectively. Later, e was redefined as

MARVIN CHARTON

122

-.8 (1 14). Regrettably, Q and e values are imprecise and tend t o vary with the reactivity ratios used in their calculation (1 15). An attempt has been made to improve the Price-Alfrey equation by the assignment of different values of e to the monomer and t o the radical derived from it (1 16). Schwan and Price (1 17) have reexamined the Price-Alfrey equation, and they write it in the form

r l = exp[-(ql -qz)/RT] exp[-7.23 . 1OZ0el(el-e2)/RT] and rl rz = exp - I7.23 . 10Zo(el-ez)2/RT] or logrl = -

(ql -q2) RT

~

--

7.23 * lozo RT

and log rl +log r2 = - 7.23RT . lozo (el - ez>’ = l o g e ) + log

(2)

Shen (1 18) suggested a formal analogy between the Hammett equation and the Price-Alfrey equation. Charton and Capato (1 19) have derived relationships between e and q values and the Hammett equation as follows. From the Hammett equation,

Similarly, Then

logkll = P i a i + h

(48)

log k12 = ~

(49)

1 0 2+ h

kz 2 log - = -Pz(U1kz 1

uz)

kll kz z log - + log -- = (p1 - p z ) ( u * - az) kl2 kz 1

Assume (53) Then

(54)

and kll kz2 log - + log - = m(ul - uZ)’ kl2 kz 1

(5 5)

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

123

From eq. (47) and eq. ( 5 9 ,

or (el

-

eZ)' = bz(ol -

(57)

from which

or

Choosing H as the standard substituent, ex =b'Jxt%-'Y@H

As uH = 0 by definition, ex = b o x t % To relate q values to a constants, combine eq. (50) with eq. (53) t o give

(3

log - = (mul t c) (al - uz) Equating eq. (62) with eq. (46) gives

. lozo el(el - ez) = mal(al RT

- (92 - ql) - 2 . 2 3

RT From eq. (58), -

-.

az) t c(ul - uz)

(qz-ql) - 7'23' 'OZo e l b ( o l - o z ) = m u l ( u l - u z ) + ~ ( u 1 - u 2 ) RT RT

(63)

(64)

Writing eq. (60) for eland substituting in eq. (64) gives - (" -")

RT

Then - (ql RT where

- 7'23

*

loZo(bul + %)b(al - az) = mol(al - az) t c(ul - az) (65)

RT

= 7'23

'OZo bZu1(al - uz)t b%(ul - uz)t mal(ol

RT

-

uz)

124

MARVIN CHARTON

Thus - (‘I

-

RT

= -mul (a, - u z )+ mu, (ul- u2)+ (c + bQ) (al - u z )

(68)

or Aq = aAu Choosing H as the standard substituent gives

Combination of eqs. (46), (61), and (71) gives, after simplification,

(3

log -

= (a‘ -t b’ul) (01

+a?)

where a a’ = - t 7.23 . lOZobeH RT

(73)

and b’ = mRT

(74)

Values of e are correlated by the up constants in accord with eq. (61) (1 19, 120). Kawabata, Tsuruta, and Furukawa (121) have proposed a revised form of the Price-Alfrey equation based on the definition e = 0 for styrene. On the basis of this redefinition, they have calculated a new set of Q values. These Q values are linear in the Hammett u constants. It is not clear from their paper whether this linear relationship is for substituents directly bonded to the carbon-carbon double bond or whether it is applicable only to Q values for substituted styrenes. Charton and Capato (1 19) were unable to obtain significant correlations between any u constants and the q values of Schwan and Price (117). Zutty and Burkhart (122) have proposed a redefinition of the Price-Alfrey equation based on ethylene as the reference system with Qo and e defined as 1 and 0, respectively. Kawabata, Tsuruta, and Furukawa (121) have reported a linear relationship between the logarithms of their Q values and the logarithms of the methyl affinities of Szwarc and co-workers (111, 123, 124). James and MacCallum (125) have found a linear relationship between the logarithms of the Qo values calculated from the definition of Zutty and Burkhart (122) and the logarithms of the rates of addition of ethyl radicals to various substituted ethylenes. Similar

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

125

relationships for both Q and Qo values have been found by Bloor, Brown, and James (126). Thus, the Price-Alfrey equation is apparently applicable to the correlation of rate data for radical addition to substituted ethylenes in uses other than vinyl polymerization. Bamford and co-workers (1 27, 128, 129) have proposed the equation log k = log k3,T t C Y U + ~

(75) for the treatment of radical addition and transfer reactions. In this equation log k3,T is the rate constant for the transfer reaction of the radical with toluene, Q and 0 are reactivity parameters characteristic of the substrate, and u is the Hammett up constant. They find that the a values are given by the relationship

a = -/.Po (76) where p2 = 5 . 3 . These authors report that eq. (75) is equivalent to the Price-Alfrey equation. They suggest that the latter is best defined in terms of e = 0 for styrene. Data for 25 sets of radical additions to carbon-carbon double bonds have been correlated with eq. (2) or eq. (30). The sets studied are set forth in Table XV. Results of the correlations are reported in Table XVI. Many of the sets were improved by the exclusion of some points. In particular, exclusion of values for phenyl and vinyl substituents almost invariably resulted in improved correlation. Of the 25 sets studied here, 1 4 gave significant correlation. The great majority of the sets which did not give significant correlation had only four to five points. Had more data been available, improved correlation would probably have resulted. It would therefore seem that rate data for radical addition to the carbon-carbon double bond are correlated by the extended Hammett equation. The results obtained are not as good as those usually obtained for correlations with the extended Hammett equation. Thus, of the 14 sets which gave significant correlation with eq. ( 2 ) , one gave excellent, one gave very good, four gave good, four gave fair, and four gave poor results. There seems to be considerably more scatter in the extended Hammett equation correlations of rate data for radical addition than is observed for other types of addition, or indeed for other systems in general. There may well be an additional factor in the reactivity of substituted ethylenes to radical addition other than those represented by the usual electrical effects. Certainly the Q parameters of Price and Alfrey and the 0 parameters of Bamford and co-workers are not well related to the UI and UR constants. As to the nature of the factor which Q and 0 represent, it has been suggested to be a resonance effect and perhaps a steric effect as well. If it is indeed a resonance effect, then it is in addition to the resonance effect represented by OR. The results obtained show that radicals can be divided into two classes depending on the signs of a and 0. The methyl, ethyl, and cyclopropyl radicals

126

MARVIN CHARTON

gave positive values of a! and 0. These radicals may be classified as nucleophilic. The difluoroamino radicals and bromine atoms gave negative values of (Y and p . These species may be classified as electrophilic radicals. The magnitude of the electrical effect is somewhat less in the case of radical addition than it was in the case of electrophilic and nucleophilic addition. In so far as the composition of the electrical effect is considered, the values of pR given in Table XVII show that for both nucleophilic and electrophilic radicals, the resonance effect seems to predominate, probably in the case of the former and almost certainly in the case of the latter. d. Carbene Addition. Skell and Cholod (140) have correlated log krel for the reaction of alkenes with dichlorocarbene with eq. (28). They obtained results comparable to those of Dubois and Mouvier (89) for the addition of bromine to alkenes. Moss and Mamantov (141) have also noted a dependence of rate of addition of dichlorocarbene t o alkyl ethylenes on the Taft steric parameters. Skell and Cholod have also fitted linear free energy relationships between rates of addition of various carbenes to alkenes. A relationship between log k and the ionization potentials of the alkene was also reported. Only four sets of data are available for the addition of carbenes to substituted ethylenes, all of them involving dichlorocarbene. The sets studied are given in Table XV. Results of the correlations are reported in Table XVI. Of the four sets studied, only one gave significant correlation. This fact is understandable because there are only four points in each set. The magnitude of the electrical effect is less than that observed for most electrophilic additions and is comparable to that found for radical reactions. As expected, dichlorocarbene is electrophilic. The composition of the electrical effect based on the limited evidence available is different from that found for electrophilic, nucleophilic, or radical addition. The value of pR for the set which gave significant correlation shows that the localized and delocalized effects are both important, with the former being somewhat the larger. e. Diels-Alder Cycloaddition. The application of the extended Hammett equation t o reaction rates for the Diels-Alder reaction was reported by Charton (142). Also studied were the para : meta ratios obtained in the addition of substituted ethylenes to isoprene. Inukai and Kojima (143) have reported a correlation of log prf(c) - log prf(u) for 2-substituted-l,3-butadienesreacting with methyl acrylate with the simple Hammett equation using the u+ constants. The prf are partial rate factors for reaction at positions 1 and 4 of the butadiene, the c and u standing for the AICIJ catalyzed and uncatalyzed reactions, respectively. Data for 21 sets of reaction rates have been correlated with eq. (2) or eq. (30). Also correlated were data on the meta : para ratio in the product of the reaction of isoprene with substituted ethylenes, and the syn-exo-anti-endo and

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

127

syn-endo-anti-endo ratios for the reaction of substituted ethylenes with perchlorocyclopentadiene. The sets studied are reported in Table XV. Results of the correlations are given in Table XVI. Best results for sets 15-63 t o 15-66 were obtained on the exclusion of the phenyl group. Of the 11 sets of substituted dienophiles studied, eight gave significant correlations. The trans1,2-disubstituted ethylenes gave generally good results. The results obtained for the cis-l,2-disubstituted ethylenes were usually inferior to those obtained for the trans-I ,2-disubstituted ethylenes. The only set of 1,l-disubstituted ethylenes studied gave excellent results. The substituted ethylene-cinnamaldehyde reaction also gave excellent results. Significant results were obtained for a correlation of the ratio of percent para product to the percent meta product in the reaction of isoprene with substituted ethylenes (set 15-79) on exclusion of the value for the phenyl group. The correlation of the ratio of percent syn-endo to percent anti-endo and percent syn-em to percent anti-endo are successfully correlated with eq. (2), the former set (15-80) after exclusion of the value for the methyl group. In the case of substituted dienes, the electrical effect is comparable in magnitude to that observed for radical addition reactions. The magnitude of the electrical effect apparently is solvent dependent, as is seen from sets 15-58 and 15-61. In so far as the composition of the electrical effect is concerned, substituted diene sets generally show pR values in the range 36-49 (pR values are set forth in Table XVII). With regard to the magnitude of the electrical effect in substituted dienophiles, comparatively low values of a! are observed for these sets. The composition of the electrical effect depends strongly on whether the cis or the trans configuration is being considered. The cis compounds show values of pR in the range 27-43, which indicates predominance of the localized effect. The trans compounds show values of pR in the range 76-95, which shows considerable predominance of the delocalized effect. The only set of 1,l -disubstituted ethylenes available also shows predominance of the delocalized effect, with a pR value of 80. The reaction of substituted ethylenes with cinnamaldehyde (set 15-78) shows a comparatively small value of a!, with a p~ value of 52. Orientation in the Diels-Alder reaction (set 15-79) shows a moderate dependence on electrical effects, with the resonance effect predominant (pR = 63). Product configuration in the Diels-Alder reaction (sets 15-80, 15-81) also show a moderate dependence on electrical effects. In this case, however, the localized effect is predominant. Following the work of Charton (142), we may draw certain mechanistic conclusions from the results reported above. Let us begin by considering the question of a two-step versus a concerted mechanism. T o define exactly what we mean by these terms, we shall consider any mechanism for which the reaction coordinate proceeds from reactants through a single transition state to products as concerted and any mechanism for which the reaction coordinate proceeds

128

MARVIN CHARTON

from reactants through a transition state followed by an intermediate and then a second transition state to products as a two-step mechanism. We may now consider what the effect of substituents on the reactivity of the diene must be in the case of the concerted mechanism. For the 2-substituted-l,3-butadienes, log kxl= a 1 2 0 1 , ~ '+ a 4 2 0

1 , +~P ~ i 2 (JR,x2

842 %,x'

(77)

+h

where a12represents the magnitude of the localized effect at C, exerted by the substituent at C2 in the transition state 6 and the other coefficients having analogous meanings. Then log kx2 = CYCJI,~~ +/~uR,+ x ~h (78) where eq. (78) is equivalent to eq. (21, = a12

8 = 8 1 2 '042

@42 >

6

I

(79)

8

Now for the 2,3-disubstituted butadienes, we may write 1% k X z X 3 = a12uI,X2 + a 4 2 0 I , X 2 +ff13u1,X3 t a 4 3 u 1 , X 3 + P 1 2 0 R , X 2 +8420R,X2 t8130R,X3 +0430R,X3

+h

(80)

If the reaction of the 2,3-disubstituted-l,3-butadienes is with a symmetric dienophile, such as maleic anhydride, the 2 and 3 positions in the diene are equivalent, and therefore a12

= ff43,

&13

= a42,

812

= 843,

PI3

= 842,

(8 1)

thus giving

1%

kX2X3 = a(uI,X2

01,X3)

+ 8((JR,X2

(82)

uR,X3)+h

equivalent t o eq. (30). Let us now consider the effect of substituents on the diene in the event of the two-step mechanism. There are three possible cases which must be examined. (a) The first step is rate determining. (b) The second step is rate determining. (c) Both steps are comparable in rate. We may begin by considering case (a) for 2-substituted-l,3-butadienes 7 and 8. Considering transition state 7, we may write 1% kxl = a 4 2 0 1 , x l + 8 4 2 %,X2 + h (83) For the 2,3-disubstituted butadienes, we obtain log kx2x3= f f 4 2 0 1 , X 2

+a4301,X3 +P42(JR,X2 + 8 4 3 % , x 3

+h

(84)

Equations equivalent to eq. (83) and eq. (84) can be written from a consideration of transition state 8. Analogous equations can be written for case

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

129

(b). For the third case, equations analogous to eq. (77) and eq. (80) may be written. On comparing the concerted and the two-step mechanisms, we conclude that the rate constants for the reaction of the 2,3-disubstituted-l,3-butadienes with symmetric dienophiles should be successfully correlated by eq. (30), giving values of a and equal to those obtained by the correlation of the rate constants of 2-substituted-I ,3-butadiene (reacting with the same dienophile) with eq. (2) if the mechanism is concerted. If the mechanism is two step, then the rate constant for the reaction of the 2,3-disubstituted-l,3-butadieneswith symmetric dienophiles should nor be correlated by eq. (30) unless X2 and X3 are identical, and furthermore, the values of a and p obtained from the correlation of the rate constants for the 2,3-disubstituted-l,3-butadieneswith eq. (30) should not be equal to the values of a and obtained for the correlation of the rate constants for the reaction of 2-substituted butadienes with eq. (2). Obviously, in this discussion it is assumed that both monosubstituted and disubstituted dienes are reacting under the same conditions with the same dienophile. The results obtained for sets 15-58 and 15-59 show that the a and p values do not differ significantly, as is shown by the student t tests. Furthermore, set l(5-59 is correlated by eq. (30) although it contains members for which X2 f X 3 . We are therefore forced to conclude that the mechanism in this case is concerted. The successful correlation of set 15-61 with eq. (30) suggests, although it does not conclusively prove, that this reaction is also concerted. The dienophiles may be treated in an analogous manner. For a substituted dienophile reacting with a symmetric diene through transition state 6, we may write (85) log k x s = a55 0 1 , ~f a 6 5 01,X 0 5 5 0 R . X + P 6 5 01,X = (O55

a65)01,X

= ff'U1,x + 0

(P55

(86)

+h

P6S)'R,X

' 0 t~h ~

(87)

while for a disubstituted dienophile,

1% kxs x6 = as 5 0 1 , x ~

a 5 6 01,X6

a 6 5 01,x5

f

(y66 'JI,X6 + & 5

01,~'

+P6501,xs +@s601,x6+P6601,x6

fh

(88)

Now for reaction with a symmetrical diene a56

= a65,

a55

'

'

Then log k X s X 6 = a55(uI,Xs

uI,X6)

= a66,

a56(u1,Xs

056

= 065,

065

= 066

O1,X6) ff155('R,XS 056(0R,Xs

= aY01,xs

+ 0 I , x 6 ) +PYOR,XS + 0 R , x 6 )

+h

(89)

+0R,X6)

'

uR,X6)

h

(90) (91)

130

MARVIN CHARTON

We may now consider the possibility of a two-step mechanism. Again, there are three cases to examine: (a) step one is rate determining; (b) step two is rate determining; and (c) both steps are comparable in rate. Let us now take up case (a). For a substituted dienophile reacting with a symmetric diene, we may have either transition state 7 or transition state 8, or both. Considering transition state 8 leads to the expression

1% kx5 = ass QI,x' For disubstituted dienophiles, we have logkXsX6 =&.5u1,Xs

tQ56u1,X6

+&S

h

OR,Xs

tPS50k,X5

tP56'R,X6

(92) th

(93)

Equations equivalent to eqs. (92) and (93) can be written for transition state 9. For case (b), the transition states 9 and 10 may be considered.

4

9

4

10

For these transition states, equations analogous to eqs. (92) and (93) may be written. For case (c), we may obtain equations analogous t o eqs. (85) and (88) which are not capable of further simplification. From the above discussion, we see that in the event of the concerted mechanism, the rate constants for the reaction of the disubstituted dienophiles with symmetric dienes should be successfully correlated by eq. (30), which should result in values of Q and 0 equal to those obtained from the correlation of the rate constants of substituted dienophiles (with the same diene under the same reaction conditions) with eq.(2). In the event of the two-step mechanism, the rate constants for the reaction of the disubstituted dienophiles with symmetric dienes should not be correlated by eq. (30) unless the two substituents are identical. In addition, the values of a and /3 obtained from the correlation of rate constants for disubstituted dienophiles with eq. (30) should not be equal to the values of a and /3 obtained for the correlation of the rate constants of substituted dienophiles with eq. (2). Although sufficient data to provide thorough tests of mechanism are lacking, it is possible to make some tentative conclusions. Sets 15-67, 15-69, and 15-71 give highly significant correlations with eq. (30). These sets include both monosubstituted and disubstituted dienophiles. Obviously, then, both monosubstituted and disubstituted dienophiles lie on the same correlation line and have the same values of a and /3. It therefore seems likely that these sets undergo a concerted mechanism. The results described above have been criticized by Dewar and Pyron (145). These authors suggest that the above analysis requires that the effect of

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

131

substituents be additive in the case of the concerted mechanism and that small but significant deviations from additivity occur in the case of the substituted dienes. We reject the proposal that these deviations are significant. If they were, (Y and /3 for the monosubstituted dienes would not be equal to (Y and /3 for the disubstituted dienes unless the deviations were of just the right magnitude and direction in all of the compounds to, in effect, cancel out. Because the latter event is of a very low order of probability, we conclude that our original analysis was probably correct and that the criticism of Dewar and Pyron is entirely unwarranted. The latter authors state that no conclusion can be reached in the case of the substituted dienophles because the rate constant for the reaction of ethylene with cyclopentadiene is unknown. This statement is true for their method of assessing additivity, w h c h depends on comparing the differences log kx5 - log with log kxsx6 - log kxs. This comparison is not required for an evaluation by the Hammett equation. The method of Dewar and Pyron suffers from the disadvantage that hydrogen is not always a well behaved substituent and often deviates from a Hammett plot. Thus, for example, the value for the unsubstituted compound deviates considerably in the Hammett correlations of substituted propiolic acids. Dewar and Pyron have made use of their method to determine the mechanism of the reaction of isoprene with substituted dienophiles. They conclude that the mechanism in this system is not one which passes through a single symmetrical transition state. This conclusion is unwarranted in our opinion because the method of Dewar and Pyron, like the method of Charton, should be restricted to the reaction of substituted dienophile with a symmetric diene. Isoprene is not a symmetric diene, and therefore the analysis is not applicable. Even if by chance the conclusion of Dewar and Pyron regarding the mechanism for this reaction is correct, it in no way implies that the reaction of dienophiles with symmetric dienes does not go through a concerted symmetric transition state. We conclude, therefore, that our analysis of the reaction of substituted dienophiles with symmetric dienes is correct and that sets 15-67, 15-69, and 15-7 1 probably d o react via a concerted symmetric transition state. We may now proceed to an analysis of the significance of the /3 values. If the transition state were close t o the product, then the fl values of the disubstituted ethylenes should be small, because in the product, the substituent is bonded to an sp3 hybridized carbon atom. Thus, it is incapable of resonance interaction. As the observed values of /3 for the trans-disubstituted dienophiles are very large, we conclude that the transition state is closer to reactants than t o products. The cis-disubstituted dienophiles show a much smaller value of /3 than do the trans compounds. It therefore seems likely that the transition state for the cis compounds will be closer to product than is the transition state for the trans compounds. The values of /3 for the reaction of the trans-disubstituted dienophiles with 9,1O-dimethylanthracene, while large, are much smaller than

132

MARVIN CHARTON

the values of 0 obtained for the trans-disubstituted-dienophile-cyclopentadiene reaction or the trans-disubstituted-dienophile-2,3-dimethylbutadiene reaction. Again, this fact may be ascribed to the location of the transition state on the reaction coordinate.

f. 1,3-Dipolar Cycloaddition. Sufficient data are extant in the literature to permit the study of 11 sets of 1,3-dipolar cycloaddition reactions. The sets studied are set forth in Table XV. The data were correlated with eq. (2). The results of the correlations are reported in Table XVI. Of the 11 sets studied, seven gave significant correlations. Of the four sets for which correlation was not significant, two had only four points: the other two had five points. With respect to the electrical effect, the reactions may be classified into electrophilic sets (set 15-84) and nucleophilic sets (sets 15-85, 15-86, 15-88 to 15-90, 15-92). The nucleophilic sets may again be divided into those for which the localized effect is predominant (sets 15-85, 15-86) and those for which the resonance effect is predominant (sets 15-88 to 15-90, 15-92), as is shown by the results in Table WII. It would seem from the results of these correlations that the 1,3-dipolar cycloaddition reaction proceeds via more than one mechanism. The mechanism seems to be strongly dependent upon the reagent. The benzonitrile oxide, 11, and diphenylnitrilimine additions, 12, both show a predominance of the localized effect, while the diphenyldiazomethane, 13, and the N-methyl-Cphenylnitrone, 14, additions show a predominance of the delocalized effect. The most obvious difference among these reagents is that in the most stable contributing structures of 11 and 12, there is a C-N double bond, whereas in the most stable contributing structures 'a .. . . ph-&-Oe 11

PhC-N-N-Ph 12

Ph,-C-NrN13

Ph-8H-NMe-O? 14

of 13 and 14, there is a C-N single bond. It is not clear at present how this structural difference is involved in the susceptibility of the reaction to electrical effects. The nature of the reagent in 1,3-dipolar cycloaddition is such that almost all such reagents are not symmetric. This fact obviates the use of the mechanistic test described above for the Diels-Alder reaction. The magnitude of the electrical effect in the 1,3-dipolar cycloaddition reaction is roughly comparable to that of substituted dienophiles in the Diels-Alder reaction. 111. SUBSTITUENTS ON CARBON-HETEROATOM DOUBLE BONDS

Perhaps the largest class of nonaromatic unsaturated systems is that of the carbon-heteroatom double bonds, including as it does the carbonyl compounds,

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

133

imines, and thiocarbonyl compounds. We shall find it useful to divide the members of this group into five categories: substituted heterovinyl sets, heterovinylidene sets, heterovinylene sets with heteroatom reaction sites, trans-heterovinylene sets, cis-heterovinylene sets, and amidines and carboxylic acids. A. Substituted Heterovinyl Sets Some physical properties of substituted heterovinyl compounds may be correlated with the extended Hammett equation. Such properties include the ionization potentials and Raman spectra. The correlation of ionization potentials with eq. (2) has been described previously. Data are extant in the literature for six sets of carbonyl compound ionization potentials. The sets studied are reported in Table XVIII. Results of the correlations with eq. (2) or eq. (30) are set forth in Table XIX. Of the six sets studied, four gave significant results (18-1, 18-2, 18-5, 18-6). The poor results obtained for the substituted propionyl derivatives (set 18-3) probably result from the fact that this set contains only two substituent types, alkyl and alkoxy or hydroxy groups. Set 18-6 is improved significantly by the exclusion of the value for X = H (set 18-6-2).The magnitude of the electrical effect is somewhat greater than that observed previously for substituted ethylenes and propenes. The composition of the electrical effect is best described in terms of the pR values, which are given in Table XX. The carbonyl compounds show values of pR of 26 or less, whereas the substituted ethylenes and propenes show pR values of 66 and 69, respectively. This large and significant difference in the composition of the electrical effect has been interpreted as resulting from the loss of an n electron in the case of the carbonyl compounds and a n electron in the case of the olefins (47). Data are available for two sets of Raman spectra of substituted heterovinyl compounds. The data TABLE XVIII Substituted Heterovinyl Sets Set

Q

18-1 18-2 18-3 184 18-5 18-6 18-7 18-8

I I I I I I

Substrate

Substituted forrnyl derivatives (HCOX) ” acetyl ” (MeCOX) ” propionyl ” (EtCOX) ” carbethoxyl ” (EtOCOX) ” benzoyl ” (PhCOX) ” carbonyl ” (X’COX2) vco ” acryloyl *’ (C,H,COX) vco ” rnethacryloyl” (H,C=CMeCOX)

Ref.

47 47 47 47 47 47 152 152

c

P

W

18-1 18-2 18-3 184 18.5 186-1 186-2 18-7 18-8

Set

h

1.27 10.42 .738 9.71 .996 9.78 4.60 10.52 -.138 9.38 2.32 9.95 .858 9.58 -49.8 1618. 5.43 1648.

P

a For footnotes, see Table XIII.

3.58 2.90 3.16 -.190 2.27 4.36 4.92 -43.9 -27.2

Q

Fb

10.35' 15.9Se 2.516' 4.522' 48.70f. 7.571' 20.47: 34.11' 90.54'

Ra .849 .862 .791 ,867 .980 .889 .965 .986 .995

.527 ,297 .949h .534 .342 .075 .163 .394 ,394

rc ,390 ,330 .267 .149 .134 .658 .424 2.87 .778

Sest

d

.192e .136e .236e .137e .0811e .353e .269e 2.86e ,775

.4631 .323' 1.42O 1.67k .249O 2.39" 1.64O 6.16h 1.67 .790g .517e 2.37" .42S0 .251e .793' 9.37' 2.54

l.lBJ

sg

ssd

4

Results of Correlations of Substituted Heterovinyl Sets

TABLE XIX

11 14 6 6 7 7 6 5 5

nq

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

135

TABLE XX Values of p~ for Substituted Heterovinyl Sets Set

PR

Set

PR

18-1 18-2 18-3 18-4

26 20 a

18-5 18-6-2 18-7 18-8

b

a

a Correlation was

53 a

not significant for this

set.

The p value was not significant for this set.

studied are reported in Table XVIII, the results of the correlations are given in Table XIX, and the pR values are set forth in Table XX. Of the two sets studied, one gave significant results. Thus, the results are too sparse to permit any conclusions to be drawn.

B. Heterovinylidene Sets The correlation of data for vinylidene sets with the Hammett equation was first reported by Charton (48). Sufficient data are available in the literature for nine sets of substituted vinylidene compounds. The sets studied are shown in Table XXI. Results of the correlations are shown in Table XXII and values of p~ are given in Table XXIII. Of the nine sets studied, six gave significant correlation with eq.(2). Of the three sets which did not give significant correlation, two have only four points, and the other set has five points. It seems entirely possible that improved correlation would have resulted had more data been available. The magnitude of the electrical effect is roughly comparable to that observed for vinylidene sets. For the substituted carbonylacetic acids, the substituted-3carbonyl propanoic acids, the anti-substituted oximino acids, and to a much lesser extent, for the substituted 3-carbonyl-2-azapropanoic acids, the localized effect predominates. For the substituted carbonylmethylene triphenylphosphorane sets (sets 21-8 and 21-9), the delocalized effect is decidedly predominant. These sets are not typical vinylidene sets, as is seen from a consideration of the contributing structures 15, 16, and particularly 17. With respect t o reaction at C', contributing structure 17 puts Ph, E C ' H-CZ-X*Ph, -P-C-C-X*Ph, II

I1

+

16

/x \

0: 8

0

0 15

+

-P-CH=C

17

21 -1 21-2 21-3 21-4 21-5 21-6-1 21-6-2 21-7 21-8 21-9

Set

21-9

21-8

21-1 21-2 21-3 214 21-5 21-6 21-7

Set

-1.57 -.479 -.384 -.342 -1.08 -.592 -.656 -.575 -8.37 -7.37

P 3.29 4.61 4.58 4.64 2.98 3.55 3.52 2.86 5.24 -.208

h

CHCI,

80% EtOH-H,O

HZO HZ0 H2O H2O HZO H*O H,O

Solvent

.942 .865 .882 .849 ,948 .874 ,936 .993 ,992 ,996

Ra 15.80i. 7.413’ 1.748’ 2.589’ 13.23’ 6.45gk 10.66J 33.92’ 117.3e 190.8e

Fb

.071 .027 .054 ,035 ,496 .482 .512 .262 .462 .763

rc

,314 .179 ,199 .162 ,120 .lo2 .0845 .0399 .355 .138

Sest d

TABLE XXII Results of Correlations of Heterovinylidene Sets

Substituted carbonylacetic acids Substituted 3-carbonyl propanoic acids ” 4 ” butanoic ” ” 5 ” pentanoic ” anti ” oximinocar6oxylic ’’ 3 carbonyl-2-azapropanoic acids ” 3-thiocarbonyl-2-thiapropanoic acids Substituted carbonylmethylene triphenylphosphoranes Substituted carbonylmethylene triDhenvlDhosDhoranes

Substrate

a For footnotes, see Table XIII.

-3.78 -1.53 -1.08 -.802 -2.39 -.781 -.907 -.368 -3.24 -5.40

(Y

lo4 kI

Q

TABLE XXI Heterovinylidene Sets

4 .528j ,830: .243m .47d .698” ,338” .273” .465” .490h 1.10”. .406m .165’ .142h .346k .0698k .160” .579e 1.49k .796g .433e

sa d

BzH

0.1 MNaCIO,

Reagent

s$

155

155

7 8 4 5 6 7 6 4 7 6

nq

48 48 48 48 48 64,5 154

Ref.

.344e .Isle .227J .181g .116e .0524e* .0467e .0404g .234e .0907m

40

25 25 25 25 25 25 25

T“C

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

137

TABLE XXIII Values of p R for Substituted Vinylidene Sets Set

PR

Set

PR

21-1 2 1-2 21-3 21-4 2 1-5

29

21-6-2 21-7 21-8 21-9

42

a b b

a

b

72 58

a p was not significant for this set. Correlation was not significant for this

set.

the substituent in a cis- or trans-vinylene position. This may be in agreement with the composition of the electrical effect for these sets. It would seem, therefore, that contributing structure 17 may be of considerable importance in the overall structure of the substituted carbonylmethylene triphenylphosphoranes.

C. Heterovinylene Sets with Heteroatom Reaction Sites It is convenient to divide the heterovinylene sets into two classes, those in which the heteroatom is the reaction site and those in which some reaction site is bonded to the heteroatom. The first of these classes will be considered here. There are three major categories of data to be considered. They are proton transfer reactions, hydrogen-bonding complex formation, and Lewis-acid complex formation. There are also three structural types to be Considered: carbonyl derivatives, thiocarbonyl derivatives, and imines. Of the three categories of data, let us begin by considering the proton transfer reactions. These are represented by pKa data. In the interpretation of these data, two major problems arise. The first of these involves geometric isomerism. Consider the protonation of some carbonyl derivative, 18. This substance may undergo protonation with an acid HA to produce either the cis- or the trans-protonated forms 19 and 20. In 18, X represents the variable substituent and Z is a constant substituent. The protonated forms are designated cis or trans, depending on the relationship of the proton to the variable substituent, X. A similar equilibrium may be written for the thiocarbonyl derivative, 21, giving the protonated forms 22 and 23, while for the imines, the protonated form 24 exists in equilibrium with the cis and trans imines, 25 and 26. Olah, White, and O’Brien (156) have reviewed the problem of “conformation” in protonated carbonyl and thiocarbonyl derivatives and in imines. They report that in the case of aldehydes and

138

MARVIN CHARTON

ketones, the predominant protonated species is that with the proton cis t o the smaller of the two groups X and Z.

20

18

II @S

II

S

h

23

II

II

26

dNyH 24

ll

9” H 22

21

N ‘H

19

II

Q“ 25

The second problem involves the measurement of pKa values for carbonyl and thiocarbonyl derivatives. Grieg and Johnson (1 57) have pointed out that the measurement of pKa values for very weak bases (11) is an inaccurate and arbitrary process. Of particular difficulty for our purposes is the fact that different carbonyl derivatives may require different acidity functions. As a result of this situation, no attempt was made to make correlations of pKa data for carbonyl and thiocarbonyl derivatives with eq. (2). Because accurate pKa values can be measured for imines, these values were correlated with eq. (2), although the conformational problem remains. The imine sets were first studied by Charton and Charton (73), who correlated them with eq. (2). No correlations of data for carbonyl or thiocarbonyl derivatives with eq. (2) are extant in the literature. Bhaskar, Gosavi, and Rao (158) have reported that AGO values for complex formation of substituted thioureas with iodine are a linear function of the Taft u* values. Drago, Wenz, and Carlson (159) have reported similar results for complex formation between iodine and substituted amides. Oloffson (160) has reported a linear relationship between -AH for the complex of substituted N,N-dimethylamides with SbCIS and the uI constants.

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

139

The sets studied are reported in Table X X N . Results of the correlations are set forth in Table XXV and pR values are given in Table XXVI. Of a total of 48 sets studied, 39 gave significant correlations. It would appear that eq. (2) is applicable to these data. This applicability is particularly significant in view of the fact that geometric isomerism is possible in all the cases examined here. Values of /3 for the cis and trans isomers may or may not be of the same magnitude. Values of (Y for the cis and trans isomers are almost certainly of different magnitude, however. It seems likely, then, that in a given set, all the members have comparable isomer compositions, because if within the same set the cis isomer is predominant for one group of set members and the trans isomer is predominant for another group of set members, it would seem that significant correlation with eq. (2) ought not to be observed. Unfortunately, it is not possible at present to determine which isomer is predominant within a given set. It seems likely, however, that the predominant isomer is that in which the reagent is bonded to the electron pair on the heteroatom, which is cis to the smaller of the two groups X and Z in the case of the thiocarbonyl and carbonyl derivatives. In the case of the imines, the proton in the free imine is probably cis to the smaller of the two groups X and Z. Thus, in the case of the substituted phenylimines (set 24-l), the predominant isomer is probably 25, where Z is phenyl. In the majority of the sets studied, the localized effect is predominant. A significant exception to this generalization is the case of the equilibrium constants for complex formation of the substituted amides with phenol and with pentachlorophenol. These sets (set 24-3 through 24-16) show predominance of the delocalized effect. It is interesting to note that equilibrium constants for complex formation of substituted N,N-dimethylthioamides with phenol and with ethanol show predominance of the localized effect. It is also noteworthy that correlation of -AH for complex formation of phenol with substituted N,N-dimethylamides shows predominance of the localized effect (sets 24-26, 24-27), as do also AvOH for complex formation between substituted N,N-dimethylamides and phenol (set 24-29), equilibrium constants for complex formation between substituted N,N-dimethylamides with iodine (Set 24-38), and -AH for complex formation between substituted N,N-dimethylamides and SbCls (set 2444). We are unable at the present time to explain this striking difference in behavior. It may be significant, however, that in all the sets in which the localized effect predominated, the W e 2 group is the constant substituent, whereas in those sets in which the delocalized effect predominates, the constant substituent is the NEt2 group or still larger groups. It is conceivable that in the case of the NMe2 group, the complex involves isomers analogous to 20 or 23, whereas in the case of the other N,N-disubstituted amides, the complex involves isomers analogous to 19.

PKa

24-1 24-2 24-3 24-4 24-5 24-6 24-1 24-8 24-9 24-10 24-1 1 24-12 24-13 24-14 24-15 24-16 24-1 7 24-18 24-19 24-20 24-2 1

Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke Ke

HNP~

Q

Set

N,N-dihexylamides

”

”

N,N-dimethylamides N,N-dimethylthioamides

piperidides

”

”

N,N-diphenylamides

”

Substituted phenylimines ” ethyl imidates ” N, N-diethylamides

Substrate

CCI,

MeNO,

H2O

Solvent

79

PhOH

pentachlorophenol

PhOH

pentachlorophenol

PhOH

pentachlorophenol

PhOH

pentachlorophenol

PhOH

Reagent

Heterovinylene Sets with Heteroatom Reaction Sites

TABLE XXIV

20 50 20 50 20 50 20 50 20 50 20 50 20 50 20 50 25 20 35

25

r C

73 73 161 161 161 161 161 161 161 161 161 161 161 161 161 161 16 1 161 162 163 163

~~

Ref.

e

c

24-22 24-23 24-24 24-25 24-26 24-27 24-28 24-29 24-30 24-3 1 24-32 24-33 24-34 24-35 24-36 24-37 24-38 24-39 24-40 24-4 1 24-4 2 24-43 24-44 24-45 24-46 24-47 24-48 acetyl derivatives

Av

Ke Ke -AH Ke -AH -AH -AH -AH

-AHO

N,N-dimethy lamides

AvOH AVOD AvOD AVOD AVOD AvOD AVOD Av Ke

N,N-dimethylamides methyl carboxylates propionyl derivatives acetyl ethyl carboxylates

acetyl derivatives ethyl carboxylates

fomyl ” ethyl carboxylates propionyl derivatives methyl carboxylates forrnyl derivatives N,N-dimethylamides

acetyl derivatives

AVOH

N,N-dimethy lamides

Ke Ke Ke Ke -AHD -AH -AH

CCl, PhH CICH,CH,Cl

CHCl,

D2O MeOD

SnCl, SbCI,

CHCl, 1,

MeOD

D,O

PhOH

EtOH

25

25 25

50 20 35 50

163 163 163 163 162 164 164 164 164 165 166 166 166 166 166 167 159 159 164 168 160 160 160 160 160 160 160

E3

24- 1 24-2 24-3 244 24-5 244 24-7 24-8 24-9 24-10 24-1 1 24-12 24-13 24-14 24- 15 24-16 24-17 24-18 24-19 24-20 24-2 1 24-22

Set

20.6 1360. -1.14 -1.15 -.633 -.386 -.997 -573 -.627 -.329 p.800 -.927 -.255 -.246 -.524 -.683 -.564 -.441 -.792 -2.03 -1.86 -1.68

a

5.41 542. -3.40 -2.81 -4.94 -5.09 -2.41 -2.22 -3.55 -3.35 -3.49 -2.76 -5.25 -4.24 -5.11 -4.36 -5.69 -6.86 -2.54 -.450 -.373 -.3 13

P 9.15 162. 1.73 1.42 1.44 1.06 1.39 1.09 1.16 .854 1.70 1.40 1.38 1.11 1.54 1.23 1.10 1.34 1.75 .975 .860 .741

h .947 .988 .9997 .994 .990 .995 .985 .980 .997 .994 .992 .99998 .996 ,996 .978 .976 .97 1 .991 .961 .975 .964 .962

Ra 17.42: 40.27' 1525.e 88.35' 51.2Si 105.3g. 32.27; 24.37' 168.6g, 88.5 1: 59.19' 29411.e 136.0g 123.1g, 21.921 20.35' 8.250' 28.09' 11.97k 18.90k 13.30k 12.36k

Fb

.200 .780 .710 .710 .710 .710 .710 .710 .710 .710 .710 .710 .710 .710 .710 .710 .713 ,713 .554 .303 .303 ,303

rc

.949 48.3 .00765 .0290 .0439 .0288 .0414 .0354 .0189 .0215 .0341 .00142 .0248 .0215 .0665 .0647 .118 ,0726 .lo7 .0826 .0889 .0824

Sest

d

4.82h 218.' .0577g ,219 .331m .217" .312k .267m .142' .162m .257k .0107e .187m .162m .501" .487" .942O .579O .314m .345: .372J .344'

d sa

Results of Correlations for Heterovinylene Sets with Heteroatom Reaction Sites

TABLE XXV

1.72j 678.O .153f: .5 781 .876' .573h .826k .70Sk .377h .428h .68d .0282e .495g .428h 1.33k 1.29k 2.38" 1.46m 1.21rn .128k .138m .127m

spd

d Sh

7 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 4 4 5 5 5 5

n"

IL)

E

24-23 24-24 24-25 24-26 24-27 24-28 24-29 24-30 24-31 24-32 24-33 24-34 24-35 24-36 24-37 24-38 24-39 24-40 2441 2442 24-43 2444 2445 2446 2447 2448

-.191 -.171 -. 126 -1.56 -.840 -3.87 -52.7 -279. -60.9 -59.5 -48.8 -6.68 -152. 120. 122. -2.49 -.837 -1.40 -2.66 -13.4 -3.95 -5.68 -13.6 -23.8 -17.5 532.

a For footnotes. see Table XIII.

-1.13 -.930 -.805 -5.38 -4.82 -5.62 -306. -388. -132. -61.1 -207. -131. -206. -87.5 -402.3 -2.17 -2.86 -1.99 -5.33 -24.0 -11.9 -21.8 -22.3 -31.5 -27.5 -281. .198 ,111 ,0658 5.91 5.69 2.99 320. 143. 148. 72.0 95.2 81.2 52.5 77.5 2252. .395 3.71 -.313 1.05 15.0 5.26 26.1 13.7 12.5 14.2 211.

.955 ,962 .926 .975 .998 .985 .99996 .980 .965 .94 1 .888 ,971 .603 .987 .989 .978 ,998 .95 1 .978 .964 .9992 .997 .99997 .996 .995 .991 10.41k 12.36k 6.035' 19.15' 124.4k 16.71' 6954.' 12.44: 20.59' 30.92e. 7.492' 16.57k .855' 19.30' 66.75f 33.72g 211.4f 4.687' 43.23f 40.19e 657.8f 166.7' 8992.' 125.9' 149.5e 84.04' ,303 .303 .303 ,554 .368 .275 .312 .344 .006 .092 .547 ,079 .997e .477 .638 .494 ,554 .275 .422 .122 .908k .341 .lo6 .557 .701, .925'

.0600 .0456 .0558 .370 .127 .404 1.07 2.88 10.9 7.54 11.0 7.24 5.71 5.75 159. ,129 .0592 .274 .257 1.47 .148 .650 .0857 .738 .565 5.95 ,2511 .191: .233 1.09' .397k 1.69m 3.30' 123.m 33.d 18.0g 56.61 22.7' 183." 17.0m 450.' .364g .174g 1.15" .573e 2.84e .842g 1.59' .214g 2.01' 2.93' 33.9

.0928m .0707m .0864" 4.21' .171m .709m 1.32h 59.2m 12.2h 8.07e 15.9' 15S0 143." 19.3' 1875.p 1.27m .694" .482" .647h 3.37' 3.44" .86d .187g 2.1 7' 1.03e 137.

.0496k .0377k .046 1" .341' .105h .409k .815' 30.1m 6.57e 2.86e 6.08e 4.949 24.9m 5.13' , 217.' .115' .0546e .278h .139' .677e .355' .625e .0615' .629' .354e 14.3

4 5 6 6

5

5 6 4 6 6 5 4 7 9 5

11 7

5 5 5 5 4 4 4 4 6

MARVIN CHARTON

144

TABLE XXVI Values of pR for Heterovinylene Sets with Heteroatom Reaction Sites

Set

pR

Set

pR

Set

24-1 24-2 24-3 24-4 24-5 24-6 24-7 24-8 24-9 24-10 24-1 1 24-12

21

24-13 24-14 24-15 24-16 24-17 24-18 24-19 24-20 24-21 24-22 24-23 24-24

b

24-25 24-26 24-27 24-28 24-29 24-30 24-31 24-32 24-33 24-34 24-35 24-36

a

75 71

71 85 81 75

b b

b C

C

d

18 a

a

a a

pR

15 C

32 49 19 a C C

Set

pR

24-37 24-38 24-39 24-40 24-4 1 24-42 24-43 2444 24-45 24-46 24-47 24-48

a a a C

33 36 a

21 38 43 39 C

was not significant for this set. was not significant for this set. CCorrelationwas not significant for this set. da and p were not significant for this set.

D. trans-Heterovinylene Sets

Data for trans-heterovinylene sets were first correlated with the extended Hammett equation by Charton and Charton (73). It must be noted that in trans-heterovinylene sets, the reaction sites and substituent are trans to each other. There are available, in the literature data for three trans-heterovinylene sets, all oximes. The sets studied are presented in Table XXVII (sets 27-1 through 27-3). Results of the cofrelations and values of pR are given in TABLE XXVII trans- and cis-Heterovinylene Sets Set

Q

Substrate

Solvent

27-1 27-2 27-3 27-4 27-5 27-6

pKa pKa pKa pKa pKa pKa

syiz-Aldoximes syn-Methylketoximes syn-Phenylketoximes anti-Aldoximes anti-Acetylketoximes anti-Phenylketoximes

H*O

"

Reagent T"C

25 25 25 25 25 25

Ref.

73,169 73, 169 '73, 169 73,169 73, 169 73,169

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

145

Tables XXVIII and XXIX, respectively. Excellent correlations were obtained for all three sets. The stereochemistry of the syn-methyl ketoximes is discussed by Charton and Charton (73). The values of p~ obtained for the transheterovinylene sets are not in good agreement with each other. Two sets gave values of 54 and 55, respectively, and the t h r d set gave a value of 35. The difference in p~ values cannot be accounted for. A value of 54 to 55 for pR suggests the possibility of some exaltation between substituent and reaction site such as that which occurs in para-substituted phenols and anilines. To demonstrate this with certainty requires that the value of pR be determined for a set of imines bearing a reaction site on the nitrogen which will not interact strongly with substituents. No such set of data is extant in the literature at the present time. TABLE XXVIII Results of Correlations for truns- and cis-Heterovinylene Sets Set

27-1 27-2 27-3 27-4 27-5 27-6 a

a

P

h

Ra

Fb

-3.35 -6.08 -4.59 -3.10 -3.28 -2.88

-3.94 -3.34 -5.64 -.627 -2.89 -1.25

10.41 11.70 11.21 11.31 8.80 11.14

.944 .999 .986 392 .950 .894

28.78e 667.2e 10.5Se

3.654' 13.95'. 7.946'

d Sh

.336 ,782 ,199 .146 .683 .175

.379 ,124 .209 .240 .359 .338

.937' .340e .431e l.lSk. .725! .80d

,773' S70' .747e 1.64' 10Sk 1.17"

.163e 10 .0758e 8 .llSe 9 .24ge 6 .176e 6 .14ge 7 -

For footnotes, see Table XIII.

TABLE XXIX Values of pR for trans- and cis-Heterovinylene Sets Set

pR

Set

pR

Set

pR

27-1 27-2

54 35

27-3 27-4

55 a

27-5 27-6

t7

a Correlation was not significant for this set.

p was not significant for this set.

No useful comparisons can be made with other systems in so far as the magnitude of the electrical effect is concerned, because unfortunately, no data are available for a set of trans-substituted enols. The values of a for the trans-heterovinylene sets can be correlated graphically with eq. (2 1) with a12= 1, X12 = 2.5. The values of p do not seem t o be a function of eq. (22).

146

MARVIN CHARTON

E. cis-Heterovinylene Sets Again, data for cis-heterovinylene sets were first correlated with the extended Hammett equation by Charton and Charton (73). There are three sets of data extant in the literature, all for oximes. The sets studied are set forth in Table XXVII (sets 2 7 4 through 27-6). Results of the correlations and values of p~ are reported in TabIesXXVIII and XIX, respectively. Of the three sets studied, two did not give significant correlation. The stereochemistry of the anti-acetyl ketoximes is discussed by Charton and Charton (73). It would seem that the localized effect is predominant in the case of the cis-heterovinylene sets. The magnitude of the electrical effect is comparable to that of the trans-heterovinylene sets. The difference in magnitude between the a values for the syn and anti phenyl ketoximes is significant and suggests that the inductive effect alone cannot account for the observed substituent effect. If the inductive effect were operating by itself, the a! values for syn and anti sets would be the same.

F. Amidines and Carboxylic Acids Amidines and carboxylic acids have been considered separately from other heterovinylene and heterovinylidene sets, because although the arnidines, 26, and carboxylic acids, 28, themselves have a heterovinylene structure, the amidinium, 27, and carboxylate, 29, ions with which they are in equilibrium have structures which are neither heterovinylene nor heterovinylidene. We shall find it convenient to discuss separately the amidines and the carboxylic acids. 1. Amidines Values of pKa for substituted amidines were correlated with the Hammett equation by Charton (190). Data are available for one set of substituted amidinium ions and one set of C-substituted-N-phenylamidiniumions. The sets studied are shown in Table XXX. Results of the correlations are set forth in Table XXXI and values of pR in Table XXXII. Significant correlations were obtained for both sets. In the case of the ionization of N-phenyl amidinium ions, the possibility of tautomerism exists. Charton (1 70) has presented arguments which suggest that the predominant tautomer is 30. The localized effect is predominant in both of the sets of amidinium ions studied.

2. Carboxylic Acids

1

Data for twenty-three sets of substituted carboxylic acid equilibria and six sets of rate data are available in the literature. It will be useful t o consider separately the equilibrium and rate data.

5

Solvent

EtOH

kr

”

5% dioxane 70% (v/v) MeOH-H,O PhH

”

D,O 80% MCS-H,O EtOH i-PrOH cyclohexanol HCONH, PhOMe Ph,O (PhCH,), 0 PhAc PhH 1,2-C6H,Cl, H,O

C-Substituted amidinium ions H2O ” ” N-phenylamidinium ions ” Substituted carboxylic acids

Substrate

PKa PKa Ka . lo5 Ka . l o 5 PKa PKa PKa PKa PKa PKa PKa PKa PKa pKa pKa PKa PKa PKa PKa Ke lo3 kr, a lo3 kr, b 10, kr log kr lo6 kr

pKa pKa pKa

30-1 30-2 30-3

30-4 30-5 30-6 30-7 30-8 30-9 30-10 30-11 30-1 2 30-13 30-14 30-15 30-16 30-17 30-18 30-19 30-20 30-21 30-22 30-23 30-24 30-25 30-26 30-27 30-28 30-29

Q

Set

TABLE XXX Amidine and Carboxylic Acid Sets

ClCH COCH C1 PhC(OMe), 5a,6pdibromocholestane Ph,CN,

SnCI, glucose

Reagent

25 30 44.08 25

28

28-30

27

5 15 18 20 25 30 35 45 25 25

25 25 0

T C

170 170 29,64, 171, 172 29,64,173 29,64,193 29,64 29,64 29,64,173 29,64,172 29,64,173 29,64, 173 174, 175 61 176 177 178 179 180 181 180 182 183 184 185 185 186 187 188 189

Ref.

a

-3.34 -1.03 -3.57 -4.07 -3.66 7.40 3.94 -3.99 -3.45 -3.27 -3.62 -5.22 -6.43 -.0765 -17.7 -19.1 -11.2 -16.9 14.0 -2.84 -9.14 -12.9 -14.0 22.00 -1.82 -.825 5.84 8.89 4.32

P 11.89 12.42 3.89 3.80 3.89 1.23 .963 4.02 3.97 3.93 3.95 4.30 6.27 11.17 8.88 8.84 5.61 4.78 -3.91 5.16 8.88 3.54 -.169 .676 1.13 ,0268 -2.30 1.64 .426

h

a For footnotes, see Table XII1.

30-1 -13.1 30-2 -21.0 30-3 -7.70 304 -7.84 30-5 -7.05 30-6 7.66 30-7 7.93 30-8 -7.69 30-9 -6.70 30-10 -6.42 30-11 -7.15 30-12 -6.19 30-13 -6.91 30-14 -12.2 30-15 -7.97 30-16 -6.66 30-17 -9.72 30-18 -9.84 30-19 8.37 30-20 -7.30 30-2 1 -5.42 30-22 -7.03 30-23 -5.71 30-24 1.72 30-25 -2.71 30-26 2.10 30-27 6.38 30-28 2.72 30-29 4.74

Set .961 .964 .931 .940 .925 .974 .983 .973 ,958 .953 .892 .977 .955 .980 .959 .958 .986 .995 .981 .980 .969 .993 .839 ,966 .975 .983 .994 .986 .949

Ra 41.98e 13.00k 26.09e 22.76e 29.58e 136.4e 170.7e 192.2e 72.8Se 53.89e 13.66f 106.2e 46.80e 11.831 17.11’ 22.228 35.8d 46.26’ 38.989 24.35’ 30.99f 111.Of , 7.138’ 27.61f 57.50e 71.67e 115.0f. 34.13’ 36.54e

Fb .297 .801. ,677’ .706k .553k ,107 .221 ,033 .229 .281 .696k .065 .112 .206 .458 .541 .837 S78 .458 .457 .Q17 .458 .602 .514 ,551 ,564 .5 1 1 .850 .578

IC

,506 .663 .330 .306 .328 .242 .245 ,339 .307 .315 .368 .235 .389 .599 ,777 ,704 .467 .309 .498 .443 .437 .254 .597 .0690 ,0818 ,0765 .201 .219 .201

Sest d

1.48e 7.41m 1.22e 1.19e .94se .520e .429e .437e .601e .665e 1.39g .503e .936e 2.56m 2.13; 1.85’ 2.74k 1.17k 1.368 1.23’ 1.22h .695g 3.41m .425h .384e .200e 379 l.llrn .959g

%d Y

Results of Correlations for Amidines and Carboxylic Acids

TABLE XXXl

st

.689g .408e 3.78P 3.38k .521e .127e .7 14g .116e .644e .108e .823e .0827e .92Ig .084ge .49se .0903e .490e .0924e .5 1le .103e .84gg .133e .74se .0836e 1.19e .134e 5.37p ,599’ 7.76m .703g 6.91k .626f 9.10“ .962! 15.5” .307’ 4.97k .45 l g ,4109 5.37O .353e 3.81k .230e 2.53h 8.24m .906p .6 10: .0589e ,644’ .0656e ,687” ,0622’ .186g 2.17k 4.27m .466k .164’ 1.52’

$

9 8 6 5 11

7

7 6 9

5

11 9 13 18 15 25 11 14 10 13 12 4 6 7 5 4 6

5

10

nq

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

149

TABLE XXXII Values of pR for Amidines and Carboxylic Acids

30-1 30-2 30-3 30-4 30-5

20 a

30-6 30-7 30-8 30-9 30-10

49 33 34 34 34

30-11 30-12 30-13 30-14 30-15

46 48

30-16 30-17 30-18 30-19 30-20

14

62

30-21 30-22 30-23 30-24 30-25

63 65 a

54 40

30-26 30-27 30-28 30-29

a (Y and p were not significant for this set. q is a linear function of O R for this set. Correlation was not significant for this set. dp was not significant for this set.

a. Equilibria. Of the sets studied, 21 gave significant correlations with eq.(2). The magnitude of the electrical effect in the case of carboxylic acid ionization is much larger than the magnitude of the electrical effect for amidinium ion ionization. Undoubtedly, the most striking result of the carboxylic acid equilibria correlations is the fact that the composition of the electrical effect appears to be solvent dependent. This phenomenon has been observed for the ionization of 2-substituted benzoic acids (1 90). The carbonyl stretching frequencies of 2-substituted methyl benzoates also show an electrical effect composition which is solvent dependent (10). The rates of reaction of 8-substituted-1-naphthoic acids with diphenyldiazomethane also show a solvent-dependent electrical effect composition (191). Although the results ‘are not conclusive, it seems that systems capable of exhibiting proximity effects may show a solvent dependence of electrical effect composition. The substituted carboxylic acids appear to behave as a system capable of proximity effects. Thus, in water, substituted carboxylic acids show a predominance of the localized effect in most sets, with p~ values of about 34, whereas in cyclohexanol, diphenyl ether, acetone, and benzene, the delocalized effect is strongly predominant, with values of pR of 6 3 to 75. This change in electrical effect with change in solvent results almost entirely from a change in the value of p , which ranges from 3.23 t o 19.1. The NH

II H , O @ + X-C-NH2 26

0 1I

H20+ X-C-OH 28

NH,

‘k

X-C-NH2 27

0

+

H,O

IC + H 3 0 i

X-C-0 29

48 a

48

MARVIN CHARTON

150

NH,

NHZ

’C X-C-NHPh

I X--C=NPh

II G X-C-NHPh

31

30

NH

32

values of 111 range only from 5.42 to 8.37 for those sets for which pR can be calculated. Thus, the range of cr is three units, while the range of 0 is about sixteen. No explanation of these observations is available at the present time. It is not certain from the limited data available how the electrical effect composition depends upon solvent properties. There does not seem to be a dependence upon solvent parameters. It must be noted that the range of UR for the data reported in nonaqueous solvents is very small, amounting to in most cases .12 u unit. Before any conclusions can be definitively drawn, it will be necessary t o study a much wider range of substituent effects. The results obtained are in agreement with the statement that the electrical effect of substituents on the ionization constants of substituted carboxylic acids includes a significant resonance effect. Taft (3) has found that the ionization constants of substituted carboxylic acids are correlated by the u* constants. He has made use of this correlation to define new u* constants and has suggested that these u* constants are a function solely of the “inductive” effect. Our results indicate strongly that this is not the case. We find that these u* constants must be a function of both localized and delocalized effects. This finding is in accord with the suggestion of Swain and Lupton (22) to the effect that u* values contain a contribution from the resonance effect. We do not regard this as significant supporting evidence for this premise, however, as we have already described our reservations concerning the Swain-Lupton treatment. By contrast, the uI constants seem to be a true measure of the localized effect. Because we have proposed that UI constants be defined from 01

= n(pKa, XCH2C02H)t d

(94)

the question is raised of whether uI constants should in fact be defined from the ionization of carboxylic acids. Aside from the empirical observation that such a derivation is in fact successful, that is, u1 constants definitely are in agreement with the values of u1 obtained by other methods, it has been shown previously (19 2) that 01,XCH,

and

Now,

= m i 01,x + C I

(95)

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

151

Then,

(102)

=mq,x+c

It is readily seen that the resonance effect in the CH2X substituent bonded to a carboxyl group is no deterrent to the definition of the 01 constants for X, as uR,XCH, is a linear function of UI, x . From eq. (95) and eq. (IOZ), it is seen that OR, XCH,

= ~ ' u IXCH, ,

+ C'

(103)

Thus, u* values for XCHz groups may be defined free of resonance effects. Values of u* for groups other than XCH2 will contain a resonance effect if they are defined from the ionization constants of carboxylic acids. b. Reaction Rates. All of the six sets studied gave significant correlations with eq.(2). The results obtained are generally in accord with those described above for equilibria. In four of the six sets studied, resonance effects were significant. Values of pR range from 40 to 54. There does not seem to be a clear-cut dependence of the composition of the electrical effect upon solvents. Comparisons are difficult, however, as the data do not refer to the same process in various solvents but are, in most cases, catalytic rate constants.

IV. SUBSTITUENTS ON CARBON-CARBON TRIPLE BONDS

We shall find it convenient to divide the data sets for substituent effects at carbon-carbon triple bonds into three categories; acetylene, ethynylene, and reactions at carbon-carbon triple-bond sets. A. Substituted Acetylene Sets

Data are extant in the literature for five sets of substituted acetylene dipole moments. The correlation of dipole moments with the Hammett equation was discussed in section II.A.l. of this work. The application of the Hammett equation to dipole moments of acetylenes was first reported by Charton (18). The sets studied here are reported in Table XXXIII. Results of the correlations are presented in Table XXXIV, and values of pR are set forth in Table X X X V .

VI w

c.

33-1 33-2 33-3 334 33-5 33-6 33-7 33-8 33-9 33-10 33-11 33-12 33-13 33-14 33-15 33-16 33-17 33-18 33-19 33-20 33-2 1 33-22 33-23 33-24 33-25 33-26 33-27 33-28 33-29

Set

VCH A v / v g . lo’

AV

vC H ”C H VCH assoc

lu

kr kr

kr

P P Lc P P

Q

. 3,

3-Substituted propiolic acids 3 ” ethyl propiolates 2 ” phenyl acetylenes

9, ’

Substituted acetylenes 2- ” phenylacetylenes 1- ” 1-hexynes 1 ” 1-heptynes 3 ” propiolnitriles Substituted acetylenes H-D exchange ” H-D ” ” H-D ” ” H-T ” Substituted acetylenes

Substrate

p-cumene

PrBu CCI, CS 2 Dioxane Bu,O MeAc DMF Pyridine Et,N

DMA

90% v/v MeAc-H,O 88.5% v/v MeOH-H,O DMF 5 M D,O (1 : 4) v/v MeOH-H,O PI* Et,O

Solvent

Carbon-Carbon Triple-Bond Sets

TABLE XXXIII

OHC-Me-N-Ph-sydnone

Et, N

Reagent

25 25 140

21 21 40 25

YC

193 193 193 193 193-5 196 196 197 198 199 199 199 200 200 201,202 201,202 201,202 201,202 201,202 201,202 20 1 20 1 201 196 203 203 18,204,207 18 205

Ref.

a

33-1 33-2 33-3 33-4 33-5 33-6 33-7 33-8 33-9 33-10 33-1 1 33-12 33-1 3 33-14 33-15 33-16 33-17 33-18 33-19 33-20 33-21 33-22 33-23 33-24 33-25 33-26 33-27-1 33-21-2 33-28 33-29

Set

4.97 8.24 7.03 7.00 -.784 4.41 3.46 7.26 6.55 -47.8 -60.8 -78.6 -34.7 50.4 2.11 -.590 -.683 20.9 35.7 11.2 8.40 60.9 14.0 -1.31 4.08 3.48 2.22 2.07 2.95 6.18

P -.I05 -.419 -.982 -.967 3.99 2.37 .909 1.22 2.08 3315. 331 1. 3255. 3311. 82.9 3.53 4.03 5.62 20.1 20.4 18.9 28.7 35.5 37.0 -2.30 2.02 2.22 .801 .749 .390 1.13

h

For footnotes, see Table XIII.

4.63 5.98 7.86 7.87 .316 6.86 7.74 12.3 5.59 -.791 11.8 -74.3 -4.27 97.1 4.39 6.01 8.00 36.3 38.6 25.8 31.3 72.5 52.3 -.335 .328 1.02 1.82 1.86 2.59 -.214

OL

.928 .964 .989 .990 .273 .9991 .990 .694 .969 .989 .910 .981 .98 1 .991 .888 .928 .949 .990 .991 .993 .962 .930 .902 .367 .883 .929 .959 .994 .966 .99 1

Ra

286.8'. 5 1.88' .9301 61.75e 89.08e 23.91' 31.77g 77.05e 135.0e , 7.438' 12.43: 17.95' 96.30e 106Se 148.4e. 18.57'. 9.674' 6.512k .702l. 8.874' 12.56' 39.61e 261 .2e 6.986l 56.04'

.040'

18.59f 19.64: 44.69: 48.82'

Fb

.836

.1lh

.I57 .147 .188 .188 .864 .434 .595 .910k .Ol 1 .156 .870k .870k .283 .009 .534 .534 .5 34 .534 .534 .534 .354 ,354 .354 .I27 .635 ,676 .413 ,396

.65 1 .630 .388 .371 .821 .0755 .197 1.13 .204 1.92 1.88 4.82 1.49 2.70 .626 .572 .636 1.47 1.64 .864 1.11 3.56 3.12 .514 .334 .291 .137 .05 34 .332 .159

d sest d

.871g 1.24h .889h .850h 4.3lP .3011 .762g 10.5" .613e 6.1lP 12.5" 32.1m 2.67m 7.05e 1.52' 1.39h 1.54g 3.58e 3.99e 2.10e 5.2eg 16.9: 14.8' 1.21' .836O .798" .214e .0837e .882" .836O

SOL

Results of Correlations for CarbonCarbon Triple-Bond Sets

TABLE XXXIV

1.12'

1.51:

1.3lg 2.301 1.42; 1.36' 1OSp , .267J .637' 5.36" l.OSe 3.63e 14.5' 37.1m 3.06e 5.69e .627O 3.08p 3.43p 7.94k 8.82h 4.65g 7.87" 25.4k 22.2' 1.11: 1.37' 1.28k .379e .150e

.340° S12" .381" .364" .721m .0747j .183' .569m .113e 1.41e 2.32e 5.96e .776e 1.42e .504g .461e .512e 1.69e 1.32e .696e .890e 2.87g 2.51e .240e .166g .171e .0513e .0217e .177" .126h

d Sh

6 6 9 8 7 7 7 7 7 7 6 6 6 12 8 7 10 9 4 5

1

4 4 5 5 11

5

9 6 5

n"

MARVIN CHARTON

154

TABLE XXXV Values of pR for Carbon-Carbon Triple-Bond Sets Set

pR

Set

pR

Set

33-1 33-2 33-3 33-4 33-5 33-6

52 54 47 47

33-7 33-8 33-9 33-10 33-11 33-12

31

33-13 33-14 33-15 33-16 33-17 33-18

a

39

9

54

pR

Set

pR

Set

PR

48 40

3d4

33-19 33-20 33-21 33-22 33-23 33-24

33-25 33-26 33-27 33-28 33-29

53

37

46

a

a

a Correlation was not significant for this set.

was not significant for this set. a and p were not significant for this set. d B was not significant for this set. 01

Of the five sets which were correlated with eq.(2), four gave significant correlations. Values of PR are in the range 50 to 54, which indicates approximately equal contributions of the localized and delocalized effects. Thus, dipole moments of substituted acetylenes could be correlated successfully with the up constants. The data available are insufficient to provide a significant test of the validity of eqs. (21) and (22). The range of uI for the constant substituent attached to the triple bond is only .14 (I unit, and the range of uR is .11 u unit. The magnitude of the localized electrical effect in the case of the substituted ethylenes is the same as that of the substituted acetylenes. The latter are significantly more susceptible to resonance effects than are the former, however.

B. Ethynylene Sets We find that it will be useful to divide the ethynylene sets into two categories: sets involving properties of the ethynyl proton in substituted acetylenes, and the other ethynylene sets.

1. Properties of the Ethynyl Proton Hydrogen-deuterium and hydrogen-tritium exchange involving the ethynyl proton in substituted acetylenes has received some attention. Rates of hydrogen-deuterium exchange have been reported to be a linear function of (I* values (197,206), as have also rates of hydrogen-tritium exchange (198). Data for three sets of rates of hydrogen-deuterium exchange and one set of rates of hydrogen-tritium exchange have been correlated with eq. (2). The sets studied are set forth in Table XXXIII. Results of the correlations are presented in

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

155

Table XXXIV, values of PR are given in Table XXXV. Of the three sets of hydrogen-deuterium exchange rates, two gave significant correlations with eq. (2), as did also the hydrogen-tritium exchange rates. In contrast to the conclusions of Dessy, Okuzumi, and Chen (197), we find there are significant resonance effects on both the hydrogen-deuterium and the hydrogen-tritium exchange rates, with PR for the former ranging from 31 to 39 and pR for the latter having a value of 54.The magnitude of the localized electrical effect for the substituted acetylenes was in the range 5.6 to 7.7. This range may be compared with a value of 12.5 obtained for partial rate factors at the ortho position of substituted benzenes undergoing hydrogen-deuterium exchange. The large difference in the magnitude of the electrical effect between orthosubstituted benzenes and substituted acetylenes may result, at least in part, from the difference in medium, the ortho-substituted benzene data having been obtained in liquid ammonia. It seems likely, however, that the greater part of the difference is a result of the difference in geometry between the two systems. In the ortho-substituted benzenes, the substituent and the proton undergoing exchange are adjacent to each other, separated only by a small amount of empty space. In the case of the substituted acetylenes, the substituent and the proton undergoing exchange are separated by the carbon atoms of the ethynylene group. Several sets of data involving the C-H stretching frequency of substituted acetylenes are available in the literature. The sets studied are reported in Table XXXIII, results of the correlations are given in Table XXXIV, and values of pR are set forth in Table XXXV. Of the four sets of v values and the one set of Av values, all gave significant correlations with eq. (2). In the majority of the sets studied, the delocalized effect was predominant, in spite of the fact that no overlap between the sigma bond to the ethynyl proton and the n orbitals of the ethynylene group is possible. This result tends to support the findings in the rates of hydrogen-deuterium and hydrogen-tritium exchange that resonance effects are of real importance. Nine sets of data involving the quantity ( A u ) / v C H % for substituted acetylenes have been correlated with eq. (2). In these data, Av is the difference between v ~ ~ , ~and , , U, C H , ~ All . nine sets gave significant correlations. The meaning of these results is obscure, however, as the quantity Av/uCH,g may not be a simple function of substituent constants. Three sets of nmr chemical shifts for the ethynyl proton have been correlated with eq. (2). Of these sets, two gave significant correlations with eq. ( 2 ) . Nevertheless, as the most extensive collection of substituents is included in the set which did not give significant correlation, it seems likely that chemical shifts of ethynyl protons are not correlated by the extended Hammett equation. This behavior contrasts with that of chemical shifts for trans- and cis-vinyl protons and is in agreement with the behavior of geminal vinyl protons.

156

MARVIN CHARTON

2. Other Ethynylene Sets Data are extant in the literature for two other sets of ethynylene compounds. The sets studied are reported in Table XXXIII. Results of correlation are set forth in Table XXXIV and values of pR in Table XXXV. The ionization constants of 3-substituted propiolic acids, which were first correlated with the Hammett equation by Charton (18), gave an excellent correlation with eq. (2) (set 22-27-1). The results are very much improved by the elimination of the value for X = H (set 33-27-2). The composition of the electrical effect corresponds approximately to that of the up constants. The magnitude of the electrical effect is significantly less than that observed for the trans-3-substituted acrylic acids. The rates of hydrolysis of 3-substituted ethyl propiolates did not give a significant correlation with eq. (2). In view of the fact that the set contained only four points, this result is hardly surprising. It seems likely that if more points were available, a good correlation would have been obtained. The paucity of data for substituted ethynylene sets is remarkable. Before any definitive conclusions concerning the transmission of substituent effects by the triple bond can be made, much further investigation is required. This field is one which is certainly worthy of further inquiry.

C. Reactions of Carbon-Carbon Triple Bonds There are almost no studies of substituent effects on additions to carbon-carbon triple bonds extant in the literature. Bowden and Price (208) have reported a correlation of rates of addition of hydrogen bromide to 3-substituted propiolic acids with the Hammett equation using the up constants. Unfortunately, there are only three substituents in the set. Sufficient data are available for a single set of 1,3-dipolar cycloaddition. The set studied is shown in Table XXXIII, and the results of the correlation are in Table XXXIV. The correlation was significant; the delocalized effect is predominant in this set. Once again, there is a remarkable lack of quantitative data on addition reactions of substituted acetylenes. This area is one which certainly merits investigation.

V. SUBSTITUENTS ON CARBON-HETEROATOM TRIPLE BONDS There is only one type of compound in this category, substituted nitriles. It will be useful to divide the data sets for substituent effects at carbon-heteroatom triple bonds into two classes, substituted nitriles and heteroethynylene sets.

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

157

A. Substituted Nitriles Dipole moments of substituted nitriles were correlated with the u* constants by Taft3 and with the up constants by Charton (18). In addition to dipole moment data, some information is available on the CZN stretching frequencies of substituted nitriles. The sets studied are reported in Table XXXVI. Results of the correlations with eq. (2) are given in Table XXXVII, and values of pR are set forth in Table XXXVIII. The correlation of the dipole moments of substituted nitriles with eq. (2) gave significant results, which were very much improved by the exclusion of the value for X = I (set 36-1-2). In contrast t o the results obtained for substituted ethylenes, acetylenes, and benzenes, the value of p obtained for dipole moments of substituted nitriles is not significant. The value of a obtained for the substituted nitriles is comparable to the value of a observed for the substituted acetylenes. TABLE XXXVI Substituted Nitrile and Heteroethynylene Sets Set

Q

Substrate

36-1 36-2 36-3 364 36-5 36-6 36-7 36-8 36-9 36-10 36-1 1 36-12 36-1 3

cc

Substituted nitriles

Solvent

Reagent T"C

VCN

PhOH MeOH

A'OH

Av

ICl

Ke Ke Ke Ke

0 10 25 40

Ref. 193 209 209 209 209 209 210 210 211 212 212 212 212

Thomas and Orville-Thomas (209) report a linear correlation of the , ~ ~ )the Taft u* constants. Their data have been quantity ( V C N , X - U ~ ~ with correlated with eq. (2). Of the five sets studied (sets 36-2 through 36-6), three gave significant results. The value of 0 for these sets is not significant.

B. Heteroethynylene Sets Caldow and Thompson (213) have reported a correlation of Av with the Taft u* constants for hydrogen bonding between phenylacetylene and substituted

m

VI c

36-1-1 36-1-2 36-2 36-3 364 36-5 36-6 36-7 36-8 36-9 36-10 36-1 1 36-12 36-13

Set

a

-2.72 -2.92 24.0 310. 189. 193. 191. -148. -177. -61.9 .730 '11.70 2.80 1.00

d h

3.52 3.45 2286. 2278. 2265. 2266. 2266. 145. 59.1 149. 1.17 1.12 1.07 .625

For footnotes, see Table XIII.

-3.92 -4.27 -83.1 -55.2 -116. -117. -118. -169. -14.0 -133. -3.45 -3.54 -3.89 -3.22

a

.788 .867 .988 .980 385 .879 389 .963 .928 .990 .9997 .998 ,998 .997

Ra

6.548i 10.64g 60.10' 36.91' 7.226' 6.775k 7.541' 94.75e 27.71:' 48.55' 966.2' 161.4k 132.6k 87.15k

Fb

d

Sest

.847 .711 5.61 S10 6.90 .427 20.6 .427 21.5 .427 20.4 .091 9.38 .510 , 3.99 .927k 4.98 .875 .0271 .875 .0644 .875 .0742 .875 .0826

.295 .300 .510

rc 1.09g .93Ig 14.3 17.5. 41.6' 43.4k 43.23j 12.6e 19.7g 32.1k .155j .370k .426k .474k

d sa

Results of Correlations for Carbon-Heteroatom Triple-Bond Sets

TABLE XXXVII

1.89" 1.59m 47.8 58.8 167." 174." 165." 33.8e 49.2g 122.' .689" 1.64' 1.89" 2.10'

spd

.398e .336e 5.79 7.12 20.1e 20.9e 19.9e 3.79e 5.49e 12.8g .0664j .158k .182m .202m

d Sh

5 4 4 4 4

10 6 6 7 7 7 18 12

11

nq

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 159

nitriles. Allerhand and Schleyer (210) have found a correlation of Au with u* for hydrogen bonding between substituted nitriles and phenol or methanol. Three sets of data are extant in the literature involving hydrogen bonding to substituted nitriles. The sets studied are set forth in Table XXXVI, results of correlations are in Table XXXVII, and values of pR are given in Table XXXVIII. TABLE XXXVIII Values of pR for Carbon-HeteroatornTriple-Bond Sets ~

Set

pR

Set

pR

Set

36-1 36-2 36-3 36-4

a

36-5 36-6 36-7 36-8

a a

36-9 36-10 36-11 36-12

a

47 71

pR

Set

pR

36-13

a

a

a a

a p was not significant for this set.

Correlation was not significant for this set. 01 is a linear function o f OR for this set.

Although all three sets gave significant correlations with eq. (2), set 36-9 shows a linear relationship between uI and UR and therefore is of no use in a determination of either the magnitude or the composition of the electrical effect. The remaining sets show widely disparate values of p ~ hydrogen : bonding with phenol gives a value of 47, whereas hydrogen bonding with methanol gives a value of 71. No reason for this discrepancy is known. The magnitude of a is also very different for the two reagents, the phenol set giving a value about twice, that of the methanol set. In any event, it seems clear from the results that resonance effects are important in hydrogen bonding to substituted nitriles. This result is in accord with those obtained for hydrogen-deuterium and hydrogen-tritium exchange in substituted acetylenes, to which hydrogen bonding in substituted nitriles may be compared, as the probable site of the hydrogen bonding is the full nonbonding orbital on the nitrogen atom. Person, Golton, and Popov (212) have found correlations between log Ke for complex formation between substituted nitriles and halogens and the Taft u* constants. The correlation of the substituted nitrile-iodine complex equilibrium constant with u* values has been questioned by Maguire, Bromley, and Banewicz (214). The data of Person, Golton, and Popov for complexes of substituted nitriles with IC1 were correlated with eq. (2). The results are presented in Table XXXVII. All four sets gave significant correlations. The value of was not significant for these sets. This result may not be meaningful, however, as the range of uR in the sets is only .1 u unit. Thus, it is not possible to draw any conclusions as to the composition of the electrical effect in these complexes.

160

MARVIN CHARTON

VI. SUBSTITUENTS ON CYCLOPROPANE RINGS Data for substituted cyclopropane rings can be conveniently arranged in five categories: substituted cyclopropane sets, cyclopropylidene sets, trans-cyclopropylene sets, cis-cyclopropylene sets, and reactions of cyclopropane rings. The correlation of data for cyclopropanes with the Hammett equation (19) and the extended Hammett equation (2 15) has been reported by Charton. A. Substituted Cyclopropane Sets

The sets studied are set forth in Table XXXIX. Results of correlations are reported in Table XL and values of PR in Table XLI. The dipole moments of substituted cyclopropanes gave a significant correlation with eq. (2). The value of PR obtained is in agreement with the values previously found for substituted vinyl compounds (section II.A.l.) and for substituted benzenes (for which a value of PR of 39 is observed). Compounds of the type RX, where R is Me, Et, i-Pr, or t-Bu, show an average value of pR of 29 (220). The results clearly demonstrate the increased resonance interaction between cyclopropyl ring and substituent as compared with an ordinary alkyl group, the former behaving in a manner like that of the vinyl and phenyl groups. The substituted acetylenes show a somewhat higher value of pR than do the cyclopropanes, substituted vinyl compounds, or substituted ethylenes, with an average value of pR of 50. The value of (Y observed for the substituted cyclopropane dipole moments is comparable to that observed for substituted ethylenes, benzenes, and acetylenes. The ionization potentials of substituted cyclopropanes also show a significant correlation with eq. (2). The value of pR obtained is comparable to that observed for substituted ethylenes and 1-substituted propenes (section II.A.2.) and is considerably above that found for substituted benzenes (for which a value of pR = 59 is obtained). This result confirms the existence of a large resonance interaction between the cyclopropane ring and substituents. The magnitude of (Y is considerably greater for substituted cyclopropanes than it is for substituted ethylenes or benzenes. Five sets of data for the near infrared absorption of substituted cyclopropanes are extant. This type of data was first correlated with the (I* constants by Gassman (221). Charton correlated this set of data with the 01, (I, and up constants and found that the up constants gave the best results. In a further study, including a wider range of substituents, Gassman and Zalar (222) reported that the best correlation was with u*. Using their data for substituted cyclopropanes and trans-1 -substituted 2-phenylcyclopropanes (sets 39-3-1 and 39-6-1) the values of p that one obtains are indeed not significant. On the exclusion of the amino group, the substituted cyclopropanes show a linear relationship between uI and U R and therefore the composition of the electrical

”

p

kr

kr

”

”

39-1 39-2 39-3 39-4 39-5 39-6 39-1 39-8 39-9 39-10

39-1 1

39-12 39-13

39-14

pKa pKa

”

A, n u

I

Q

Set

Solvent

nuns-1-Substituted 2-phenylcyclopropanes ” 1 ” 2,2dimethylcyclopropanes ” 1 ” I-cyclopropane carboxylic acids HZO ” 2 ” 1 ” 2 ” 3,3-dimethyl-lcyclopropane carboxylic ” acids ” 2,3disubstituted cyclopropylmethyl-3, Sdinitrobenzoates ” 2-Substituted-1-bromocyclopropanes cis-2-Substituted-3,3dimethyl-l-cyclopropane carboxylic acids ” 2 ” 1-bromocyclopropanes

Substituted cyclopropanes

Substrate

Cyclopropane Sets

TABLE XXXIX

50%EtOH-H20

130

130 25

100 50%EtOH-HzO Cellosolve-H,O

15 Cellosolve-H,O 60%MeAc-HzO

25 25

219

219 61

218

19,215 215 216 211 211 216 216 19 19,215 19

T C Ref.

80%Methyl

Reagent

h)

m

w

a

39-1 39-2 39-3-1 39-3-2 39-4 39-5 39-6-1 39-6-2 39-7 39-8 39-9 39-10 39-11 39-12 39-13 39-14

Set

h

3.95 .419 2.95 10.26 .000965 1.637 -.0162 1.636 -.00938 1.637 .0176 2.230 -.000225 1.635 -.0166 1.635 -.0158 1.644 -5.47 4.91 -.828 4.69 -1.55 7.56 -7.45 .632 -14.1 -1.56 - .84 1 8.09 -21.0 -1.33

P

For footnotes, see Table XIII.

4.96 1.19 -.0278 -.0204 -.0219 -.0276 -.0181 -.0139 -.0187 -6.38 - 1.94 -3.19 -3.06 .4.62 -.990 3.93

a

Fb

.981 39.10g .999 218.5' .957 54.8Se .985 143.7e .950 18.47g .969 38.28' .945 20.87f .996 2g2.pe .99994 4142.' .999 240.8' .975 48.24:: .995 93.82' .9999993 333333.f .9994 434.5' .865 1.485' .980 11.87'

Ra .113 .071 .477 .773g .646 .594 SO8 .615 .753 .689 .071 .407 .755 .064 .918 .064

rc

d

SlY

d

Sl3

.l .27k .350 .578g. .0483 .0869' ,204 .00181 .00296e .00242O .00263e .00115 .00456' .00558h .00934" .00192 .00117 .00323 .00507 .00146 .00329g .00211p .000401 .00106e .O022Sg .00088d .000132 .000413h .488k .111 ,298' .208e .0874 .217h .1 78h .0918 .242g .00213 .0146g .O1loe .486 .629 .0655 581" 1.03O .0882 4.32m 5.59O .582

Ser t

d

Results of Correlationsfor Cyclopropane Sets

TABLE XL

.233m .O36Og .000791e .00051e .00158e .000914 .00108e .00029Se .000103e .075Sg .0362e .0471e .00249' .0589 .0706g 524"

d Sh

4 4 4 4

5

6 4 13 12 7 8 8 7 4 4 8

nq

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 163 TABLE XLi Values of pR for Cyclopropane Sets Set

pR

Set

39-1 39-2 39-3-2

44 71

394 39-5 39-6-2

a

pR

Set

pR

Set

pR

Set

46 46 30

39-10 39-11 39-12

33 71

39-13 39-14

54

39-7 39-8 39-9

pR

a U I is a function of OR for this set.

b p was not significant for this set. Correlation was not significant for this set.

effect cannot be determined (set 39-3-2). The trans-1-substituted 2-phenylcyclopropanes, however, on exclusion of the amino group, show a significant value of 0 (set 39-6-2). The 2,2-dimethyl-l -substituted cyclopropanes also show a significant value of 0 (set 39-7). On the other hand, the substituted cyclopropane data of Weitkamp and Korte (217) do not give a significant value of 0. We are forced to conclude from these results that the composition of the electrical effect in these data remain open to question and that further investigation is required. B. Cyclopropylidene Sets

Only one set of data is available in this system, and it has only four points. Although significant correlation is obtained, the results can in no way be considered conclusive. It is fascinating to note that the value of pR for this set is 46, which corresponds approximately to the P R value of the up constants. An explanation for this composition of the electrical effect has been proposed by Charton (19). It is obvious that this system is in need of further investigation.

C. trans-CyclopropyleneSets Data are extant in the literature for four trans-cyclopropylene sets. Of these, two are disubstituted (sets 39-9 and 39-1 1). Positions trans-2 and trans-3 are completely equivalent in cyclopropanes bearing the reaction site at position 1. These sets have been correlated with eq. (30). The other two sets have been correlated with eq. (2). Three of the four sets studied gave significant correlations. The fourth set had only four points. The results obtained clearly show a significant resonance effect. They clearly demonstrate that the trans-cyclopropylene system does involve a resonance interaction between the substituent and the cyclopropane group. The trans-cyclopropylene system again

164

MARVIN CHARTON

is one which will require further investigation, although the general outline of its behavior seems clear.

D. cis-Cyclopropylene Sets Only two sets of cis-cyclopropylene data are extant in the literature, and each set has only four points. It is therefore not surprising that neither set gives a significant correlation with eq. (2). This system is obviously in great need of further study to ascertain the presence or absence of steric effects and the magnitude and composition of the electrical effect.

E. Reactions of Cyclopropane Rings Only one set of data for the addition of bromine to substituted cyclopropanes has been reported (223). In this set, the substituents are of the type XCHz, and therefore the data were correlated by Charton with the oI constants. Once again, this area requires extensive investigation.

VII. SUBSTITUENTS ON HETEROCYCLOPROPANE RINGS In conformity with our previous approach, we classify substituent effects on heterocyclopropane rings into four categories. They are substituted heterocyclopropyl sets, heterocyclopropylidene sets, heterocyclopropylene sets and heterocyclopropanes with heteroatom reaction sites. A. Substituted Heterocyclopropyl Sets There are unfortunately no data extant in the literature for substituted heterocyclopropyl sets. B. Heterocyclopropylidene Sets Again, there are no data for heterocyclopropylidene sets extant in the literature. It would be of great interest to have such data available. C. Heterocyclopropylene Sets Once more, no data are extant in the literature for heterocyclopropylene sets. This area certainly merits investigation, as it would be interesting and instructive to be able to compare substituent effects on the heterocyclopropane ring with those on the cyclopropane ring and the heterovinylene group.

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

165

D. Heterocyclopropanes With Heteroatom Reaction Sites There are two sets of data extant in the literature for this system. The sets studied are shown in Table XLII. Results of correlations with eq. (2) are given in Table XLIII. Values of PR are described in Table XLIV. Barely significant results were obtained for both sets. Undoubtedly, the results would have been better had more data been available. Regrettably, no conclusions can be based on such limited evidence. This system requires further work. TABLE XLII Heterocyclopropane Sets Set

Q

Substrate

Solvent

Reagent T"C

42-1 42-2

AVOH

Substituted oxiranes

tetrachloroethylene

PhOH

Ke

TABLE XLIII Results of Correlations for Heterocyclopropane Sets

P

Set

a

42-1 42-2

-1.77 -1.31

Set

42-1 42-2

h

Ra

188. .975 -177. .451 .973 -1.85

Sest d

6.94 .0594

sa d

sad

Fb

18.90k .738 17.61k .738

sf

132." 16.1g 58.1k .0497m 1.12" .138k

TABLE XLIV Values of pR Set

PR

Set

PR

42-1

a

42-2

b

a

rc

p was not significant for this set. a and p were not significant for this set.

nq

5 5

20 20

Ref.

224 224

166

MARVIN CHARTON

VIII. SUBSTITUENTS ON OTHER UNSATURATED SYSTEMS It will be convenient to consider under one heading all those unsaturated systems which do not fall under any of the sections previously discussed. There are four categories which are included in this catch-all heading. They are pyridones, quinones, multiple substitution at nonequivalent sites, allenes and cumulenes, and conjugated dienes and polyenes.

A. Pyridones Pyridones have not been considered previously because the reaction site can undergo resonance effects involving more than one type of interaction. Localized effects, assuming they are field effects, will not be affected. If the localized effect were an inductive effect, which seems very unlikely, then there would be two paths to the reaction site, Consider the pyridones for which data are available. Three sets are extant. They are the 3-substituted 4-pyridones, 33; the 5-substituted 2-pyridones, 34; and the 3-substituted 2-pyridones, 35. In each of these systems, the substituent is conjugated with the nitrogen atom by one path and in

33

34

35

a vinylidene position by the other. It is therefore impossible to assign these compounds to any of the categories previously described. The results of the correlations are set forth in Table XLVI, and values of P R are given in Table XLVII. Significant correlations were obtained for all three sets. The results show a predominance of the localized effect, as is shown by the p R values. From previous results for trans-vinylene systems, if the influence of the enone moiety in 33 and 34 could be ignored, it would be predicted that pR values in the neighborhood of 50 might be found. Obviously, then, the pyridone structure as a whole must exert an influence on the resonance effect observed in these compounds (again assuming that the localized effect is represented only by a field effect).

B. Quinones When substituted quinones undergo reaction at the carbonyl groups, the substituent does not exert the same effect on each carbonyl group, Consider, for

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 167

example, the 3-substituted 1,2-benzoquinones, 36; the 4-substituted 1,2-benzoquinones, 37; and the 2-substituted 1,4-benzoquinones, 38. In 36, the substituent is in a vinylidene

b'.

&I

+x0

X

36

37

38

position with respect to one carbonyl group and a divinylene position with respect to the other. In 37, the substituent is in a vinylidene-vinylene position with respect to one carbonyl group and a vinylene position with regard to the other. In 38, however, the substituent is in a vinylidene position with respect to one carbonyl group and a vinylene position with respect to the other. As a result of this, quinone carbonyl group reactions and properties do not fit into any of the categories previously examined. We have therefore chosen to examine them here. The largest category of data which falls into this classification is that of quinone oxidation-reduction potentials. The application of the Hammett equation to quinone oxidation-reduction potentials was first studied in some detail by Charton (248). The subject has since been treated in depth by Zuman (249,250). Horner and Geyer (238) have found a linear relationship between both up and up values and the oxidation-reduction potentials of 4-substituted 1,2-benzoquinones. It is then taken up again here because no previous attempt has been made to correlate the data with eq. (2) or with eq. (30). The sets studied are given in Table XLV. Results of correlation are reported in Table XLVI and values of PR in Table XLVII. Of the 45 sets of quinones and quinonediimines studied, 3 1 gave significant correlations. Of the fourteen sets which did not give correlation, twelve had only four points. The remaining two sets had five points. Thus, had sufficient data been available, the results undoubtedly would have been much improved. The Eo values for 2-substituted 1,6benzoquinones (sets 45-4 through 45-7, 45-10) show an average value of PR of 59. Thus the resonance effect predominates. For most of these sets, the up constants are not the best parameters for correlation. By contrast, the electron reduction potentials (set 45-8) show a PR value of 39, which indicates predominance of the localized effect. The 2,s-disubstituted 1,4-benzoquinones differ distinctly in their behavior from the 2-substituted 1,4-benzoquinones in that they show an average PR value of 53. The one-electron reduction potentials of these compounds show about the same composition of the electrical effect, with a value of pR of 50. The only set of Eo values available for the 2,6-disubstituted 1,4-benzoquinones gave a PR value of 51, comparable to the values observed for the 2,s-disubstituted 1,Cbenzoquinones. The 2,3,5,64etrasubstituted 1,4-benzoquinones have

K 00

45 -2 3 45-24

45-1 45-2 45-3 45 4 45-5 45-6 45-1 45-8 45-9 45-10 45-1 1 45-12 45-1 3 45-14 45-15 45-16 45-11 45-1 8 45-19 45-20 45-21 45 -22

Set

Q

H2O

75% EtOH-H,O, 95%EtOH-H,O, 1 1 AcOH-H,O MeCN

PhH H2O 95% EtOH-H,O, 95% EtOH-H20, MeCN PhH

0.2 M HCl 0.1 N HC1 1.0 N HCI AcOH-H,O MeCN

H,O

3-Substituted 4-pyridones 5 ” 2 3 ” 2 ” 2 ” 1,4-benzoquinones ” 1,4 2 *’ 1,4 2 2 ” 1,4 2 ” 1,4 2 ” 1,4 2 ” 1,4 2,5-Disubstituted 1,4-benzoquinones 2,s ” 1,4 ” 1,4 2,5 2,5 ” 1,4 ” 1,4 2,5 ” 1,4 2,6 2,3,5,6-Tetrasubstituted1,4-benzoquinones 2,3,5,6 1,4 1,4 2,3,5,6 2,336 1,4 2,3,5,6 1,4 N4,N4-Dimethyl-2-substituted 1,4-benzoquinone diiminium perchlora tes N‘ ,N4-Diethyl-3-substituted 1,4-benzoquinone diiminium ions N’,N’ ” 2 ” 1,4 ))

Solvent

Substrate

Other Unsaturated System Sets

TABLE XLV

20 20 20 25 25 25 20 25 25 25 25 0.5 N HCl 25 25 1 N HCI 15 25 25 0.1 N NaOH 25 1.0 N HCl 25 20 25 25

T“C

237 231

13 13 13 225 226,221 226,221 228,229 230 230 231-3 234 226,227 226,221 230, 235 231-3 231-3 230 226,221 228 230 230 236

Ref.

c

\o

m

45-25 45-26 45-21 45-28 45-29 45-30 45-31 45-32 45-33 45-34 45-35 45-36 45-31 45-38 45-39 45-40 4541 4542 45-43 45-44 45-45 45-46 45-41 4548 45-49 45-50 45-51 45-52 45-53

E,

vCO pKa pKa pKa

uco

E‘ Eo

Eo Eo Eo

E,

E,

E,, E,:,

E,.$

E,, E, E,

E, E,.,

E, E,

E,

E, EA

E, E, E,

3-Substituted 1,2-benzoquinones 6 ” 3-methoxy-l,2-benzoquinones 3 ” 4,Sdimethyl 3,6-Disubstituted 1,2-benzoquinones 4-Substituted 1,2 ” 1,2 4 5 ” 3-methoxy-l,2-benzoquinones 4,s-Disubstituted 1,2-benzoquinones ” 192 3,4 3,4,5,6-Tetrasubstituted1,2-benzoquinones 2-Substituted 1,4-naphthoquinones ” 1,4 2 ” 1,4 2 2 ” 1,4 2Chloro-3-substituted 1,4-napthoquinones ” 1,4 2 ” 3 2-HY~IOXY-3-” 1,4 4-Substituted 1,2-naphthoquinones 4 ” 1,2 3,3’-Disubstituted-Diphenoquinonediimines 3,3‘ 3,3‘ 3,3’ 3,3’ 3,5,3’,5’, Tetrasubstituted diphenoquinones 2-Substituted 1,4-naphthoquinones Disubstituted oximes (X,C=NOH) Disubstituted dioximes [ (XC=NOH],] truns,trans-5-Substituted 2,4-pentadienoic acids CHCl, CCl, H2 0

H, 0 50% MeAc-H,O 6 N H,SO,

1-10 EtOH-H,O

H, 0

25 25

25 25 0 25 40

4cr

50% EtOH-H,O, 0.1 N HC1 EtOH-H,O, 0.1-0.2 N HCl 25

PhH H, 0

25 25 25 25 25 25 25 25 25 25

238 238 238 238 238 239 238 238 238 238 240 240 24 1 242 240 240 240 243 243 244 244 244 244 244 245 246 13 13 15,241

z

45-5 45-6 45-7 45-8 45-9 45-10 45-1 1 45-12 45-1 3 45-14 45-15 45-16 45-17 45-18 45-19 45-20 45-21 45-22 45-23 45-24 45-25

54-4

45-1 45-2 45-3

Set

-.185 . I 15

.I05

-5.91 -4.89 -4.54 .211 .166 .I66 .271 .545 .235 .197 .172 .248 .211 .604 .I89 .I 36 .341 .178 .213 .522 .448 .340

OL

4.68 -2.53 -2.95 .358 .222 .222 .452 .348 -.447 .222 .190 .287 .332 .612 .I99 .I42 .488 .308 .395 .345 .332 .271, -.226 -.00908 .I45

P 10.48 11.58 11.85 .699 .690 .686 .700 -.5 1 I -1 .I 3 .696 .652 .644 .699 --.464 .683 .683 -.312 .681 .703 -.551 -1.18 .235 -.226 -.291 .783

h

1 .ooo .99 1 .990 .985 .9997 .98 1 .980 .9999 .999 .997 .990 .960 .959 .994 .986 .995 .987 .992 .999 .726 .415 .95 1

.9993 .998 .997

Ra

363.1J 392.7e 180.1' 25907.f 54.583 48.51: 32.201 783.1' 12.82' 71.93e 4430.e, 291.1' 266.1e, 46.93' 23.811: 17.27' 43.54: 36.22j 46.26' 54.66f 88.0Sf 184.9k 4.446k .208' 9.507k

Fb .591 .050 .059 .859 .405 .405 .793 .819 ,819 .377 .991 .244 .620 .757 .687 .374 .702 .769 .818 .590 .590 359 .286 .464 .487

IC

.lo6 .116 .162 .000247 .0920 .0104 .00926 .00444 .0324 .0115 .00119 .00896 .0110 .0426 .0233 .0242 .0438 .0348 .0209 .0990 .0662 .00400 .07 14 .0805 .0130

Sest

d

Results of Correlations for Other Unsaturated Systems

TABLE XLVI

.0343e .0161" .0143" .310° .030Sk

.0513'

.0673h .027Sg .025Sh .0366k .039dk .0221

.0155' .O 14ge

.361' .181e .254g .000994' .022Oh .0233h .0347h .O 1 9 d .129" .0210e .O 1OSg

d

sfl

.0853' .0570h .0410k .0759' .148p .0386k

.OSllk

'

2.44" .40@ S58' .00254g .0230h .0244h .089 I .0456k .332" .0212e .048Ok .0134J .014ee .139' .0387g .0328' .0774m .0363'

.105g .0868e . I 22e .000246' .00720e .00763e .00889e .00424g .0309' .00638e .01 26e .01 16h .0072Se .0279' .01 39e .0177e .0438k .0273g .0209' .07 I Og .0474e .0398h .0374e .0583' .00984'

d

Sh

4 6 6 4 11 5 5

5

7 6 4

5

4 4 9 5 4 6

5 5 5

4 6 5 4

nq

2

45-26 45-27 45-28 45-29 45-30 45-3 1 45-32 45-33 45-34 45-35 45-36 45-37 45-38 45-39 45-40 45-41 45-42 45-43 45-44 45-45 4546 45-47 45-48 45-49 45-50 45-51 45-5 2 45-5 3

-.00271 .365 .I31 .239 .270 .248 .284 .0948 .280 .330 .314 .352 .318 .331 .882 .0790 .390 .341 .293 .306 .206 ,216 .237 -2.66 45.1 -4.53 -3.39 -1.15 9.66 4.4 1

11.55

.741 .711 .713 .783 .833 .735 .795 .774 .793 -.141 -.291 .480 .474 -.lo3 .275 -.293 .610 .594 .919 .937 .924 .905 .896 1635. 1673.

a For footnotes, see Table XIII.

.206 .I86 .I01 .138 ,0855 .I46 .175 .I03 .I56 .225 .I75 .347 .132 .0589 -1.15 -.0413 .202 .0896 .I66 .I69 .296 .29 1 .292 4.43 44.6 -11.5 -15.9 -.870 .973 8.862' .985 16.77' .97 1 8.253l .967 87.2Se 50.83k .995 .924 I 7.59f 1334.' .9998 .917 2.634' 38.56l .994 42.96f .978 1374.k .965 18.16k .974 7 1.63f .990 12.14' .927 44.96' .994 1.703' .794 167.9g .997 13.32g .918 3207.' .99992 .999999 192307.f 4.524' .949 5.048' .954 6.131' .962 11.27l .979 24.00f .943 196.7g .997 98.2Ie .990 70.80k .996 .6 12 .859 .07 1 .189 .859 .lo9 .818 .556 .859 .271 .705 .949k .229 .204 .973 .024 .309 .369 .556 .556 .556 .556 .556 .726 .I76 .864 .288 .008 .0142 .00812 ,0328 .0160 .00262 .0207 .00163 .0330 .0184 .0240 .0330 .O 164 .0134 .0474 ,0177 .0278 .0113 .0556 .00117 .000159 .0343 .0321 .0297 1.96 5.29 .305 ,493 .0376

. I 18p .06 16m .0326m .0833m .029Sm .0677" .02 14e .0236e .O1OSk .0269k .0458h .0537g .00346h .00800h .0476" .0514" .018Sk .0473m .0579h .0360: .0731 .195" .0933k .166m .035d .0316g . I 17' .O70Sg .1 5fim .309m .0450" .07770 .021 3g .0448' .0769g .109" .00366g .00339h .000458g .000494g .0989" .107" .loo" .0928m .0927" .0858m 4.18' 1.60" 7.39e 10.4g 1 .4Sk 1 .97m 1.13e .806h .14Sk .0987k

.0142h 4 .00809g 4 .0244' 4 .00699e 15 .O026lg 4 .0132e 9 .00163g 4 .025 2' 4 .0184h 4 .0176g ' 7 .0252g 5 5 .0153g .0090Ie 6 .0453k 7 . I 39" 4 5 .0274g .00961e 5 .0432e 8 .00089ge 4 .000121e 4 .0262h 4 .0246h 4 .0227h 4 1.9Se 4 3.38e 9 .247e 5 .24Ie 7 .0196g 4

MARVIN CHARTON

112

TABLE XLVII Values of pR for Other Unsaturated Systems Set

PR

45-1 45-2 45-3 45-4 45-5 45-6 45-1 45-8 45-9 45-10 a

a

34 39 63 51 51 63 3b9 53

45-11 45-12 45-13 45-14 45-15 45-16 45-11 45-18 45-19 45-20

C

54 53 50 51 51 b

63 65 40

Set

pR

Set

pR

Set

45-21 45-22 45-23 45-24 45-25 45-26 45-21 45-28 45-29 45-30

43 53

45-31 45-32 45-33 45-34 45-35 45-36 45-31 45-38 45-39 45-40

63 t2

45-41 45-42 45-43 45-44 45-45 45-46 45-41 45-48 45-49 45-50

56

63 16

$4

pR

Set

pR

%6

45-51 45-52 45-53

18

a

51

64 t4

50

p was not significant for this set. Correlation was not significant for this set. 01 is a function of O R for this set. a was not significant for this set.

an average PR value of 6 4 for correlations of E,. The correlation of the one-electron reduction potentials (set 45-20) gives a pR value of 40. These results are comparable to those obtained for the 2-substituted 1,4-benzoquinones. The Eo.S values of N4, N, -dimethyl-2-substituted 1,4-benzoquinonediiminium perchlorates gave a value of 53 for PR, significantly less than that observed for the 2-substituted 1,4-benzoquinones. As the set (set 45-22) had only four points, however, no definitive conclusion can be reached. The 3-substituted 1,2-benzoquinones give a PR value of 53. The 4-substituted 1,4-benzoquinones are much more sensitive to resonance effects, with pR values of 63 and 76. The latter value, stemming as it does from a four-point set (set 45-30), is much less reliable than the former (set 45-29), particularly as the former set is very extensive in both number and type of substituents. The PR values obtained for the 5-substituted 3-methoxy-1,2-benzoquinones (set 45-3 1) and the 4,5-disubstituted 1,2-benzoquinones (set 45-32) support the value obtained for set 45-29. The 2-substituted 1,4-naphthoquinones have values of 60 and 74 for pR . The latter value seems high. The 4-substituted 1,4-naphthoquinones show a PR value of 6 6 (set 45-42), in good agreement with the value for 4-substituted 1,2-benzoquinones. The 3,3'-disubstituted diphenoquinone diimines give a PR value of 64. The results obtained for the 2-substituted 1,4-benzoquinones and the 2,5-disubstituted 1,4-benzoquinones show that the composition of the electrical effect is independent of medium. It must be noted that in contrast to the early work cited above, in which correlations were carried out with up, for which pR is 50, best results for most substituted quinone oxidation-reduction potentials show a pR value of about

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

173

60, which corresponds more closely to the UP' substituent constants. There is sufficient variation in pR , however, to require that for best results, correlations should be carried out with either eq. (2) or eq. (30). The magnitude of cr for the 2-substituted 1,&benzoquinones ranges from .166 t o .271, depending on medium for correlations of Eo. The one-electron reduction potentials (set 45-8) show a value of (Y twice as great. The values of (Y observed for the 2,5-disubstituted 1,4-benzoquinones and for the 2,3,5,6-tetrasubstituted 1,4-benzoquinones are comparable to those found for the 2-substituted 1,.l-benzoquinones, in so far as correlation of Eo is concerned. The one electron reduction potentials for the former compounds are also comparable to that for 2-substituted 1,4-benzoquinones. Correlation of Eo for 2,6-disubstituted 1,4-benzoquinones gave a value of cr somewhat less than that observed for the 2-substituted 1,4-benzoquinones. The 3-substituted 1,4-benzoquinones gave a value of cr significantly less than that observed for the 2-substituted 1,4-benzoquinones, as do also the 4-substituted 1,4-benzoquinones. The 2-substituted 1,4-benzoquinones show a wide range of cr for correlation of Eo, from .132 to .347. The 4-substituted-l,2-naphthoquinones show (Y from .090 to .202, depending on whether the Eo values were obtained potentiometrically or polarographically. The 3,3'-disubstituted diphenoquinone diimines show cr values comparable to those of the 2-substituted 1,4-benzoquinones. In addition to the oxidation-reduction potentials data, two sets of infrared carbonyl stretching frequencies were correlated with eqs. (2) and (30). Of these, one set, vCo for 2-substituted 1,4-naphthoquinones, gave significant results, with p R of about 50. While the other set did not give significant correlation, it contained only four points. Although the sharp difference between PR for vco and pR for Eo correlations of 2-substituted 1,4-naphthoquinones is worthy of note, it should not be discussed until it is confirmed by further work. e

C. Multiple Substitution at Nonequivalent Sites Let us consider a system X"X"GY, where X" and X" are substituents at nonequivalent positions m and n of the skeletal group G, which also bears the reaction site Y. Neglecting interaction terms, we may write for the correlation of the quantity Q the expression, ~ m X n = ~ u I , X m t ~ u R , X mXn+&OR,Xnth t~~I,

(104)

In the special case for which Xm- X", we have %mXn = (%I

%&I,

Xm = (Pm +O&R,

Xm

or Qxmxn =01'u,,~m+ $ u R ~ m + h equivalent to eq. (2).

'

(105) (106)

174

MARVIN CHARTON

Two sets of data involving multiple substitution at nonequivalent sites have been examined. The sets studied are reported in Table XLV (sets45-51, 45-52). Results of the correlations are set forth in Table XLVI. Significant correlations were obtained for both sets of data. Sets of the type XmX"GY in which m and n are nonequivalent and in which Xm # X" cannot be handled by correlation with eq. ( 2 ) . Such sets can be correlated with eq. (107):

Q x ~ = xPmurn,xm+Pnon,xn ~ +h

(107) where u, and on are substituent constants defined for or applicable to the m and n positions of the group G . Thus, consider the system 39,

39

in which u, can be used for X3 and up for X4'. Then for 39,

D. Conjugated Dienes and Polyenes Sufficient data are extant in the literature for only one set of substituted dienes. In this set (set 45-53, Table XLVI) is included the value of pKal for muconic acid. This value is reported by Yanovskaya, Strepanova, and Kucherov (247) to be 2.70. Such a value seems impossible, as the pKal for fumaric acid, in which only one double bond intervenes between the carboxyl groups, is 2.98, according to these authors. We therefore calculated pKal for muconic acid from the correlation obtained for the i1pns-3-substituted acrylic acids and the oIand oR constants for the H02CCH=CH substituent. A value of 3.68 was calculated. We have therefore assumed that there is a typographical error in the results of Yanovskaya, Strepanova, and Kucharov, and have used the value of 3.70 for pKal of muconic acid. Correlation of the data with eq. (2) gave significant results. As is predicted from calculations of a and 0,p R is greater than 50, a value of 57 being obtained as compared with a predicted value of 62 to 65. The difference between the predicted and observed values may well result from the fact that there were only four points in the set. It is meaningful, however, that in contrast to most systems XGC02H where G is arylene, vinylene, ethynylene, etc., for which pR is about 50, the value of pR for the trans,trans-divinylene group has a significantly larger pR value. The value of a for the truns, truns-5-substituted 2,4-pentadienoic acids suggests that the conformation in solution is the s-trans (between C3 and C4). Rough estimates give a value of OL of about .8 for the s-trans and of about 1.0 for

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

175

the s-cis conformations. The observed value is -370. As the set included only four points, no definitive conclusion about conformation can be reached. No other data on substituted conjugated dienes are extant in the literature. Of the five nonequivalent positions on a conjugated diene system, no study has been made of the remaining four. Thus the vinylidene (X'), vinylene (X')), vinylidenevinylene (X3), and cis,truns-divinylene positions of 40 remain unexamined. No studies of X2

WY

x5

I X -

x4n

x

3

40

substituent effects on polyene systems extensive enough for correlation with eq.(2) have ever been made. Obviously, this is an area which is worthy of further investigation.

E. Allenes and Cumulenes There are absolutely no data sets for substituted allenes or cumulenes in the literature. This is a situation which should be remedied at the earliest opportunity, as data on these systems would be of considerable theoretical interest.

IX. CONCLUSIONS We shall find it useful to consider three categories of conclusions; transmission of electrical effects, composition of electrical effects, and other conclusions.

A. Transmission of the Electrical Effect In the application of the extended Hammett equation to the system XGY, where X is a substituent and Y is a reaction site, both of which are attached to the skeletal group G, the question of the degree of transmission of substituent effects through G arises. The transmitivity of G is measured by the magnitude of LY and 0. Now,

a = f(G, P, T, Sv, Y, Rg.

. . .)

(1 09) That is, LY is a function of the skeletal group G and its ability to transmit the substituent effect, as well as of pressure, P; temperature, T; solvent, Sv; reaction site, Y; and reagent, Rg. We may write for LYG OG

= 71,Ga

(1 10)

176

MARVIN CHARTON

where T I G represents the transmission character of the group G to the localized electrical effect and w is a term characteristic of all the other variables upon which a! is dependent. Thus, w = f(P, T, Sv, Y, Rg. . . .)

(111)

Now let us consider some reference skeletal group Go. For convenience, we shall choose as the reference skeletal group the p-phenylene group. We define

The quantity YIG is therefore a measure of the transmission of localized electrical substituent effects through the group G relative to the transmission of localized electrical substituent effects through the group G o . Similarly, for the transmission of the delocalized electrical effect, we may write

and

where ~ R Grepresents the transmission capability of the group G to the delocalized electrical effect and w is again a term characteristic of all the other variables upon which P is dependent. Then we define

~ YRG are collected in Table XLVIII. Values of 7 1 and That values of yI and YR vary with the reaction and the reaction conditions is readily seen from the results reported in Table XLVIII for the trans-vinylene group. Values of yI for this group range from 1.01 to 3.28. That the value of y1 is dependent upon the reaction is no surprise. Charton has shown (251, 252) that the yI values may be calculated from the Kirkwood-Westheimer equation in the form

where r and 6 are given in Figure 1. Obviously, r and 0 will depend on the geometry of Y as well as the geometry of G. It is for this reason that p - p relationship of Miller (253-6) shows deviations. It is uncertain why the yIvalues show variation for the same reaction in different solvents. Thus, 71 for the

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 177 Y

Fig. 1. Definition of r and 0 .

ionization of 3-substituted acrylic acids is 2.26 in water, 1.54 in 80% methylcellosolve-water, and 1.01 in 50% ethanol-water. Before any explanation is proposed for this phenomenon, it would be useful to examine a much larger group of compounds in a wider range of solvents. The variation of YR with reaction may be explained by the observation of Charton (257) that yR = m q t c

(117) where q is the charge on the atom bearing the reactiog site calculated by the method of Dewar and Longuet-Higgins in the species YGCH, . As m is a function of Y, it is not surprising that yR will vary with Y. In view of the variation of y1 and YR as a function of Y, the transmission of electrical effects is best compared for a given Y under constant reaction conditions. The most suitable reaction for purposes of comparison is the ionization of carboxylic acids in water at 25". The first observation we may make concerning yI is the fact that all systems in which X and Y occupy vicinal positions and are approximately coplanar (orthophenylene, cis-vinylene, and trans-l,2-cyclohexylene) show similar values of yI of about 2.4. The YR value of the cis-vinylene group is significantly less than that of the orthophenylene group. The value of 71 for groups G with two carbon atoms is, for nonvicinal systems, in the range of about 2, with trans-vinylene having a value of 2.26; ethynylene, a value of 1.86; trans-1 ,2-cyclopropylene, a value of 1.94; and dimethylene, a value of about 1.6 (the results at 18" are for a wider range of substituents and substituent types than those at 25" and are therefore preferable). Introduction of a constant methyl substituent onto the trans-vinylene group causes an increase in yI. Values of YR for the trans-vinylene group and the ethynylene group are about the same: 2.09 and 2.07, respectively. Values of 71 for groups with three atoms between substituent and reaction site range from 1.53 for COCH2CH2 to .907 for CONHCH2. Values of 71 for groups with four atoms intervening between reaction site and substituent include p-phenylene, with yI = 1.OOO, and trans,trans-divinylene, with y1= .970. The YR value for trans,trans-divinylene is significantly less than that predicted from eq. (1 17), however. The discrepancy may result from the fact that the set from which Y R

c 4 00

cisCPh=CHcisCMe=CH-

PhCN,

50% EtOH-H,O EtOH 50%EtOH-H,O HZ0

H2O

trans-CMe=CHtrans-CH=CMecis-CH=CH-

H, 0 80%Methylcellosolve-H ,O 50%EtOH-H,O OHH,O 70% (v/v) dioxane-H20 MeOH MeOH Ph2CN, EtOH

Ph,CN,

80% Methylcellosolve-H,O

H2O

Reagent Solvent

50%EtOH-H,O

CO,H

C0,Et

CO,H

CO,H

Y

transCPh=CH-

iransCH=CH

G

Values of 7 and pR

TABLE XLVIII

25 25 25 30 25 25 25 25 18.8 35 30 30 25 25 25 25 25 25 30 25 25

T

15

2.25 2.55

d

55 51

3.43 2.65 1.56 3.25

49 45

d

39 71

42 50 59 d

d

63 52

C

C

C

C

C

C

C

C

C

C

C

C

C

C

C

C

C

10

10 10

a b

50a

25b 49 44 40 48 56

Ref. pR

1.23 1.70 3.44 d

d

1.OOoa .333b 2.31 1.13 1.11 2.09 1.99 3.01 3.05 1.87

1.OOoa

l.OOOb 2.40 1.45 1.62 2.26 1.54 1.01 1.79 1.75 3.28 1.73 1.72 2.42 2.08 2.84 2.58 2.41 1.30 2.02 2.35 3.14

TR

TI

W

4

c1

a

’’

,

80% Methylcellosolve-H,O HzO

H2O

50% EtOH-H,O

H2O

50% EtOH-H,O

25 25 25 25 25 25 25 25 18 25 25

25

25 25 25 25 25 25 25 25 25

4.14 3.39 2.12 4.25 2.68 2.70 ,870 1.94 1.90 6.38 1.86 7.69 .56 1.18 3.78 1.53 .907 1.31 1.61 2.32 3.95

.873

d

.656

.828 .923 5.41 2.07 3.99 .38f 1.47 1.57

1.15

2.92

d d

d d

By definition. Calculated from c for urn. This work. B was not significant for this set. This set is of the type XY,that is substituent and reaction site are directly joined to each other. Calculated from for 0;.

trans-2-cyclo-C, H,, CH,

trans-CH=CHCH, WCCH, WCCH,CH, O=CNHCH, CH,CH,

f16H4CH2

trans, tmns-CH=CH-CH=CHtrans-cyc1o-C,H, trans-cycloC,H,Me, cycld: ,Ha CZ nonee

cis-CPhH=C

CH,=Ccis€PhH=C-

42 0 0 0 0

d

29

55

57 30 33 46 53 34 40

d d

41

d

17

d

c

29 29 19 29

c

9

c c

c

180

MARVIN CHARTON

was calculated contains only four members and therefore the value of 0 is uncertain. The value of YR calculated from eq. (1 17) for the XC02H in which there is no group G is in very good agreement with the observed value. The vinylidene group, the trans-CPh= C- group, and the methylene group, all of which have one atom intervening between the substituent and the reaction site, all show y~values of about 4. The cyclopropylidene group is an exception to this observation, with yI of 6.38. As there were only four points in the set from which a was obtained, this deviation may not be real. The C-CPh=C group has a somewhat low value for yI of 3.39. The introduction of a methylene group between G and Y results in a decrease in y1by a factor of about .5,as is shown by the yIratios of p-C6H4CH2 to p-C6H4, trans-CH=CHCH, to trans-CH=CH, and COCH2 CH2 to COCH2 . Values of y1 for the COCHz and COCH2CHz groups are larger than would be expected from the number of atoms intervening between substituent and reaction site. It is of interest to compare the ratios ac/aT and &//3T for the vinylene group. Values are reported in Table XLIX. Of the 1 1 sets for which the comparison can be made, 10 sets have aC/aT> 1. If the localized effect were an inductive effect, the values of ac would of course be equal to those of aT, and therefore the ratio aC/aT would show values scattered about 1.000, with an equal probability of being greater or less than 1.000, The observation that in general the values are greater than 1.OOO excludes the inductive effect as the sole factor in the localized effect and strongly suggests that the localized effect is a field effect. From eq. (1 17), we would predict that 0c should equal 0~ and should be scattered about 1.000 with an equal therefore the ratio probability of being more or less than one. This result is in fact observed, with five values greater than and six values less than 1.OOO. TABLE XLIX Values of 'YC/'YT and pc/PT cis Set

trans Set Q

Y

Solvent

"C/"T

PC/PT

12-5 12-6 12-1 1 12-12 12-15 12-16 12-17 12-18 12-20 12-21 12-19

8-1 8-3 8-8 8-5 8-15 8-16 8-17 8-20 8-22 8-23 8-21

CO, H

H,O 50% EtOH-H,O

1.07 1.28 1.13 1.15 1.17 1.10 1.08 1.77 ,757 1.52 1.37

.746 1.08 .85 1 .744 1.48 1.29 1.21 SO4 .851 .goo 1.05

PKa

7 ,

H2 0

kr " "

v

6 v

z

C0,Me H H H

EtOH t-BuOH EtOAc CCI,

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

181

B. Composition of the Electrical Effect From the previous discussion, in which it was pointed out that both a and 0 must be functions of Y, we see that PR, which is a function of a and 0, must also be a function of Y. It will therefore be convenient to compare the composition of the electrical effect transmitted by various groups G with Y and the reaction conditions held constant. Again, the most useful reaction for this purpose is the ionization of carboxylic acids in water at 25". Not only are there more sets of data available for this reaction than for any other, but the sets studied for this reaction generally include more substituents than d o sets for other reactions or under other reaction conditions. The value of PR observed for the trans-vinylene group is 48. Substitution of a methyl group on the trans-vinylene group gives comparable values of 51 and 55. The ethynylene group gives a comparable value of pR of 53, as does the ortho-phenylene group, which shows a value of 49. By contrast, the cisvinylene group shows a pR value of 39. The cis-vinylene group bearing a constant trans-methyl substituent gives a value of pR of 45, in much better agreement with the ortho-phenylene value. The cyclopropylidene group also gives a comparable value, with pR of 46. This system requires further investigation, however. The p-C6H4CHZ group shows a pR yalue of 40. Surprisingly, the trans-CH=CHCHz group shows a value of 55. This result is unexpected, as the methylene group prevents direct resonance interaction between the carboxyl group and the substituent and vinylene group. It would be useful to verify this observation by a more detailed study of this system. Of particular interest is the value of pR of 42 observed for the CONHCH? group. This value is significantly larger than the pR value of 29 observed for the COCH? group. If this result is verified, then it would seem that the CONHCH? group has a significant contribution of the structure HO-C=N-CHz -: that is, there is considerable double-bond character in the C-N bond. The vinylidene group shows a pR value of 17. Surprisingly, the trans-styrylidene group has a value of pR of 41. Again, it would be useful to verify this result. The trans-cyclopropylene group shows a value of pR of 30, thus clearly establishing the ability of the cyclopropylene group to transmit resonance effects t o some extent. The trans,trans-divinylene group has a pR value of 57, somewhat greater than the pR values observed for p-phenylene, trans-vinylene, and ethynylene. C. Other Conclusions Of the 389 sets studied, 294 gave significant correlations. In the majority of the sets which did not give significant correlation, only four or five points were

182

MARVIN CHARTON

extant. There is no doubt that had more data been available, significant correlation would have resulted in at least 90% of the sets studied. We conclude, therefore, that linear free energy relationships in general and the extended Hammett equation in particular are applicable to data for nonaromatic unsaturated systems. Our results show the importance of resonance effects in all the systems studied. Furthermore, there is considerable variation of PR with structure. It is therefore difficult in most cases to recommend correlation with the Hammett equation with use of simple substituent constants such as urn, ,:u up, or ui. We therefbre recommend that data for nonaromatic unsaturated systems be correlated with the extended Hammett equation for best results. References 1 . Hammett, L. P., Physical Organic Chemistry, McGraw-Hill, New York, 1940. 2. Jaff6, H. H., Chem. Rev., 53, 191 (1953). 3. Taft, R. W., in Steric Effects in Organic Chemistry, M. S . Newman, Ed., Wiley. New York, 1956, p. 565. 4. Stock, L. M., and H. C. Brown, Adv. Phys. Org. Chem., I , 35 (1963). 5. Leffler, J. E., and E. Grunwald, Rates and Equilibria of Organic Reactions, Wiley, New York, 1963. 6. Palm,V.,Russ. Chem. Rev., 31, 471 (1961). 7. Wells, P. R., Chem. Rev., 6.3, 17-4 (1963). 8. Ritchie, C. D., and W. F. Sager, Jr., h o g . Phys. Org. Chem., 2, 323 (1963). 9. Wells, P. R., Linear Free Energy Relationships, Academic Press, New York, 1968. 10. Charton, M.,Prog. Phys. Org. Chem., 8, 235 (1971). 1 1 . Wells, P. R., S. Ehrenson, and R. W. Taft, Prog. Phys. Org. Chem., 6, 147 (1968). 12. Jaffk, H. H., and H. L. James, Adu. Heterocyclic Chem., 3, 209 (1964). 13. Evans, E., and J. DeHeer, Trans. Faraday Soc., 47, 801 (1951). 14. Harnsberger, H. F., E. L. Cochran, and H. H. Szmant, J. Am. Chem. SOC., 77, 5048 (1955). 15. Charton, M., and H. Meislich, J. Am. Chem. SOC.,80, 5940 (1958). 16. Hine, J., and W. C. Bailey,J. Am. Chem. SOC.,81, 2075 (1959). 17. Hine, J., and W. C. Bailey,J. Org. Chem., 26, 2098 (1961). 18. Charton, M., J. Org. Chem., 26, 735 (1961). 19. Charton, M., 1.Chem. Soc., 1964, 1205. 20. Taft, R. W., and 1. C. Lewis,J. Am. Chem. SOC.,80, 2436 (1958). 21. Taft, R. W.,J. Phys. Chem., 64, 1805 (1960). 22. Swain, C. G., and E. C. Lupton, Jr., J. Am. Chem. SOC.,90, 4318 (1968). 23. McDaniel, D. H., and H. C. Brown,J. Org. Chem., 23,420 (1958). 24. English, P. J. Q., A. R. Katritzky, T. T. Tidwell, and R. D. Topsom, J. Am. Chem. SOC.,90, 1767 (1968). 25. Sheppard, W. A., private communication to Ref. (24). 26. Taft, R. W., private communication to Ref. (24). 27. Oue, S., and C. C. Price, J. Am. Chem. SOC.,80, 3425 (1958). 28. Fraenkel, G., and J. P. Kim,J. Am. Chem. Soc., 88,4203 (1966). 29. Charton, M., J. Org. Chem., 29, 1222 (1964). 30a. Brownlee, K. A., Statistical Theory and Methodology in Science and Engineering, 2nd ed., Wiley, New York, 1965.

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS

183

30b. Crow, E. L., F. A. Davis, and M. W. Maxfield, Statistics Manual, Dover, New York,

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184 72. 73. 74. 75. 76. 77. 78. 79. 80. 8 1. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116.

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r W

X

'ZH3

PhS PhSO PhSO, CH,CO,H CH,CO; C1,CH CO, Ph

-CH,CH, Me Me

\ -Me

Q

NO, HC, CH,OH CH,Cl CH, Br BuCH, CHO OAc As0,HSeCN SMe COCl trans-PhC, H, Me, C=CHCH, CH, CMe=CHCH, CH,

Ref.

.ll .01 .31 .42 .09

0.00

f.

''

.44 j .02 1 .O1

.36 .42

.64 .35

01

X

-.22 .05 .13 -.06 -.23 .03 .14 -.I 1

f

' '

CH,CO,Et CONH, PO(OEt), PO(OCH,CH,Cl), EtSO, EtCO HO,CC,H, HOCH,C,H,

-.15

i-PrCH,CH, PhCH, Bz trans-MeC, H, 2-fury1 Me,N CH,OMe CH,OBz CH,NMe:BrCH,F 3-O,NC6H, CH,CHIOH MeCHOHCH,

cc1,

CH,OAc CICH,CH, O

p

Ref.

.14 a -.09 -.06 -.03 -.06 -.11 .07 -.12 -.03 .08 -.35 .19 -.12 m -.14

OR

aa

'' '

'

Ref.

.29 .21 .09

.52 .52

' '

hh

;;

.14 bb .05 cc

.15 .25 .18 .19 0.00

.10

.29

.43 -.03

01

Substitutent Constants from Sources other than Ref. (23) and Ref. (29)

APPENDIX 1

hh

gg

;;

' 'dd

bb

' '' ''

"

'

Ref.

.09 mm -.05 mm -.11

-.08 .09 .08 .08 .13

-.05 -.lo

-.08 -.05 0.00 -.04 -.01 -.lo -.13

-.13 0.00

.02 -.12 -.14

OR

c

W 0

.20

-.07 .08

.27

-.01

.14 .03 .17 -.12

' '

zk

' ' '

Ref.

.34 jj -.04

01

' ' ' '

'

' '

-.09 -.12 -.40 -.34 -.12 -.21 -.15 k .17 kk -.07 -.53 'I -.05

-.05

-.01

.I1 jj -.11

O R Ref.

cycloC6Hl Oi-Pr cycloC,H, Me,C=CH NHPh ' MeO,CCH,CH, 4C,H,NO, 442, H,MeO C,H,CH, r-BUS C,H,O r-BuCH, cycloC,H,CH, BzO

X

.23 .35 -.02 -.02 .45

.22 .09

.05

.15

.26 -.02

01

'' ' ''

''

Ref.

-.21 -SO -.15 -.12 -.23

-.08

'k k ' 'k

'

nn

Ref.

-.19 b 00 -.12 k -.55 -.09 .01 -.I8

-.12

UR

Calculated from the up value obtained from the equation up, XCH, = 0.522 UI,X -0.131. Ref. (37). M. Charton, J. Org. Chem., 34, 1882 (1969). Ref. (8). Calculated as in a from up values reported by Ref. (2). From M. Charton, Abstr., 154th Meeting of the American Chemical Society, Chicago, 1967, S 137. M. Charton and B. I. Charton, J. Chem. Soc. B, 43, (1967). Calculated from the up value estimated by the method of M. Charton, J. Org. Chem., 28, 3121

Calculated from om and up values reported by J. K. Kochi and G. S. Hammond, J. Am. Chern. Soc., 75, 3452 (1953).

(1963).

j

i

I

Calculated from the pKa of 4-nitro-[2,2,2] bicyclooctane-1-carboxylicacid using p = 1.65. The value of UR was calculated from UR = up - UI by use of the value of up given by Ref. (23). Ref. (215). Calculated as in a from up values reported by 0. Exner and I. Jon&, Coll. Czech. Chem. Cornrnun., 27, 2296 (1962).

a

Ph,Si EtOCH, PhO MeO,CC,H,

'ZH3'

Bu0,C nCsH13 NCCH, CCI, CH, EtO,CCH,CH, MeO,CCH, 04C,H,NMe, AcNHCH, Me,SiCH,

X

c. W c.

JJ

'

"

Assumed equal to 01 and O H for C,Il,CH,CII,. Assumed equal to 01 and O K for C,II,CH,CH,CH,. Calculated from up reported by H. H. Szmant and G. Su1d.J. A m . Ckern. Soc., 78, 3400 (1956). Calculated from up reported by C. Y . Meyers, B . Cremonini. and L. Maioli, J. A m . Ckem. Soc., 86. 2944 (1964). Estimated as described by M . Charton, Abstracts, 148th Meeting o f the American Chemical Society, 1964, p. 56-V. M . Charton, J. Org. Ckem., 34, 1877 (1969). up estimated from a plot of ul vs. up for CIInC13-n, U R calculated as in ". Ref. (37), calculated as in '. ( I S ) , calculated as in '. " Ref. Ref. (60), calculated as in '. W Ref. (170), calculated as in '. Calculated as in ',assuming U ~ , C H , O M=~U ~ , C H , O H , Calculated from pKa for C,H,CH,CO,H. Calculated as in a from up values reported by E. Berliner and L. €I. Liu, J . A m . Ckern. Soc., 75, 2417 ( i i 5 3 ) . Calculated from pKa of HOCH,CH,CH,CO,H. bb M. Charlon,J. Org. Ckem., 30, 3346 (1965). cc Calculated from pKa for ClCH,CH,CH,CO,H. dd From up value reported in ref'. of k, calculated as in a. ee Calculated from urn and up values reported by L. D. Freedman and H. H. Jaffk, J. A m . Ckem. Soc., 77,929pY55). Assumed equal t o substituent constants for PO(OEt), . gg Assumed equal t o O R for MeSO,. h h M . Charton,J. Org. Ckem., 36, 266 (1971). k Calculated from um and up values estimated as in . Assumed equal t o substituent constants for C0,Et. kk Calculated from um and up values reported by R. A. Benkeser, C. E. DeBoer, R . E. Robinson, and D. M. Sauve, J. A m . Chem. SOC., 78, 6 8 2 (1956). I' Calculated as in a from up values reported by M . Charton, J. Ckem. SOC., 5884 (1964). mm , up, x-0.0179. Calculated asin a from up valuesestimated from the equation up, t r a n s - x c , =~ 0.388 nn Calculated as in ', assuming up, cyclohexyl = up, j.pr, 00 Assumed equal to U R for trans-MeC,H,.

rn

192

MARVIN CHAKTON

APPENDIX 2: DATA USED IN CORRELATIONS Abbrevia1:ions used in this appendix are as follows: Vi 1-Vn

vinyl vinylidene (e.g., 1-MeVnCI is CH,= CClhAe)

2-Vn

vinylene e.g., trans-2-MeVnCl is

2-Pn 3-Pn 4-Pn

ortho-phenylene meta-phenylene para-phenylene

Set

Ref.

Data

2-1

Table 2

H , O ; F , 1.427;C1, 1.44;Br, 1.117;1, 1.27;Me, -.364;Ph, .13;C,H, .43;CF,, 2.45;CN, 3.89;NOZ,3.44;Me3Si, 0 H , . 1 3 ; P , 1.36;C1, 1.41;Br, 1.56;Me, -.72;Ph,0;CN,4.17;N02,4.54 H, .364;F, 1.85;C1, 1.97;Br, 1.69;Me,O;Ph, .72;C,H, .94;CN,4.53 H, -1.417;CI,O;Br,O;I, .39;Me, -1.69;Ph, -1.4 H, -1.452;CI,O;Br,O;Me, -1.97;Ph. -1.41;Me3Si, -1.71 H, -3.89;Me, -4.53;Ph, -4:17;CN,O H, .364;F, 1.60;C1, 1.69;Br, 1.51;Me, -.503;Ph, .76;CN, 3.69 H, .13;C1, 1.93;Me, -.76;Ph, .5 H , O ; F , 1.417;C1, 1.43;Br, 1.41;Me, -.38 CN, 10.91; CH,OH, 9.67;CH2C1, 10.04;CHZBr,9.7;CF3, 10.90; C,H3,9.07;C,H, 9.87;Me, 9.73;Et,9.58;Bu,9.46;BuCH2,9.54; F , 10.37;Cl, 10.00;Br, 9.80;13, 10.51;CHO, 10.10;Ac.9.91;CO,H, 10.90; OMe, 9.93; OAc, 9.19 Me, 9.13;Et, 9.06;Pr, 9.16; Br, 9.30; H, 9.73;CHO, 9.73 F , 2.55;Ph, 3.84;H, 4.26;Me, 4.65;Bu. 4.80;As03H-, 4.225; SeCN, 1.896; PO,H-, 3.5 Br, 1.84;C1, 1.97;1, 2.24;Ph, 3.74;H, 3.88;Me, 3.62 H, 5.38; Me, 5.10; Br, 3.55; C1, 3.73 H,5.18;Me,4.95;Cl, 3.40;B1,3.38;1,3.56

(

2-2 2-3 2-4 2-5 2-6 2-7 2-8 2-9 2-10

2-1 1 5-1 5 -2 5-3 54 5 -5 5 -6 5-7 5-8 5 -9 5-10 5-1 1 5-12

5-13 5-14

Table 5

Me.-'

--/")

Br,3.03;C1,3.02;1,3.30;F,:i.71;Ph,4.71;H,4.44;Me,4.82 H. 5.77;Me,6.10;Br,4.28;CI., 4.30 H, 5.55; Me, 6.00; C1, 4.10; BI, 4.15; I , 4.34 CI, 3.22; H, 4.70; Me, 4.96; A;iO,H-, 4.61 CN, 3.04;CO2Et, 3.36;CONH2,3.95;H, 5.12;Me,4.42 Br, ,190; CI, ,158; H, .218; Me:, 3.44 Me, 14.88; Ph, 6.46; CO,Et, 2.38; H, .46 H, O;alkyl, .44;cycloalkyl, .71;CH,O, .67;CH,I, .67;CH,S, .53; CH,CI, .72;CH,Br, .72;CN, .23;CO, l.lO;CO,H, 1.00; CO,R, .84; CHO, 1.03; NCO, 1.37; COCI,l.lO; OR(aliphatic), 1.18; OR(conjugated), 1.14;OCOR, 2.09; aromatic, 1.35; C1, 1.00; Br, 1.04; NR,(aliphatic), .69; SR, 1.00; SO,, 1.58 F, -.84; OMe, -1.10; C1, -.9'7; Br, -1.16; Ph, -1.36;CN, -.20; i-Pr, -.34; H, 0 F, 388.72; C1, 371.08; Br, 381.35; I, 389.09; OMe, 386.0; SMe, 380.7; CN, 328.10; CHO, 375.62; H, 318.5

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 193 Set 5-15

Ref.

5-16 5-17 5-18

Data Me. -.40;H,O;Ph,-1,36;Br, -1.16;CI, -.97;CO2Me,-.66;Ac,-.95; CN. -.20;NO,, -1.79 H. -.19;CO,Me, -.83;Me, -.51;Ph,-1,2l;Cl, -.99 H. -.55;CO,Me, -1.15;Me. -.75;Ph, -1.55;Br, -1.29 H, -.38;CO,Me, -.98;Ac, -1.32; Me, -.91;Cl, -.87;Br, -1.37; Ph, 1.66; CN, .44; CHO, -1.32; COCI, -1.26 ;NO,, -2.18 H. .37;CO,Me. -.43;Me, .08;CI, -.55;Br, -.62;Ph, -.91;CN, .02; CHO, --.70;COCI, -.76;NO,, -1.62; Ac, P.68 CN. -206.0;CI, -234.3; Br, -248.0; Me, -216.3 H, -.89;Me, ---1.54;CI,-1.98;Br, -2.24;COZMe, -1.41;Ac, -1.61; COCI, -1.63; Ph, -2.23 H. -.76;CO,Me. -1.24;Me, -1.43;Ph, -2.12 H,4.255;Cl, 3.79;Br,3.71;1, 3.74;OMe,4.85;N0,,2.58;CH2C1, 4.140;CI;,, 3 . 1 5 ; C 0 2 H . 3.396; CO,Et, 3.396;Ac, 3.238;CO;, 4.301; Me. 4.693; Et,4.695; PI, 4.703; i-Pr, 4.701; trans-2-PhVn, 4.427 -

5-19 5-20 5-2 1 5-22 8-1

rable 8

-

Me

8-2

8-3

8-4 8-5 8-6 8-7 8-8 8-9 8-10 8-1 1 8-12 8-13 8-14 8-15 8-16 8-17 8-18 8-19 8-20 8-21

8-22

0

--CH,CH;, 7.05; Me, C=CHCII,CH, -C=CIICH,CH, ; 7.12; I Me Me Me CO,H, 5.40;CO;. 6.52 H,5.50;PhS,5.78;PhSO,4.30;PhSOz,3.79;Ph,5.77;Me,5.53;~, CH,CI, 4.88 Me, 4.96; H, 4.65; Ph, 4.82; CI, 4.03; MeO,C, 3.452; EtO,C, 3.468 C1,4.07;Br, 3.98;1, 3.90;H,4.44;Me,5.12;Et,5.15;C02Et, 3.26 Ph. 4.5; H, 3.880;C1, 3.57; Br, 3.592; I, 3.636 H, 5.38;Me,6.13;Br, 4.85;C1,4.98 H . 5 . 1 8 ; M e , 6 . 0 0 ; C I , 4 . 7 7 ; B r , 4.72;1,4.79 H, 4.37; CI, 4.12; Me, 4.507; Et, 4.516; CH,CO,H, 4.28; CH,CO;, 4.70 H. 10.95;Ph, 10.23;CONH2,9.67;C0,Me,9.40;CN, 7.81; 4-Me2 NC, H, , 10.29 H. .779; Me, .130;CO;. .158;CO,Et, 2.235 H.41.1;Me.4.20;C1,149.;Br,209.;i, I,159;OMe,2.24 H, 20.0;Me. 9.07;CI, 5.13;Br, 5.99;I,4.10;OMe,4.70;N02, 2.62 Me, .61;H, 1.27;C1, 2.48;Ac,4.03;HOZC, 3.36a;C1,CH, 2.36; CI,C, 5.39; O,N, 21.8 H, 1.32;Me, .587;C1, 2.68;Br, 3.31;1, 3.20;OMe, .450;NO,, 21.5 H . ,447; Me. ,181; CI, 1.1 1; Br, 1.49; I , 1.44 H. .230;Me, .0573;CI, .933;Br, 1.13; I, 1.06 H. 1.00; CI, .6; Me, 17; Ph, 5 0 H . 1.00;C1, 1.01; Me, 95; Ph, 8800 H, 1735;Me, 1730;Cl. 1733;Br, 1733;I, 1733;OMe, 1713 H. 0: alkyl, -.29; cycloalkyl, -.30; CH,O, -.07; CH,I, -.07; CH,S, -.15; CH,CI, .07; CH,Br, .07; CN, .58; CO, 3 1 ; CO,H, .74;CO,R, .56; CHO. 1.21; NCO. .35;COCI, .99;OR(aliphatic), -1.28; OR(conjugatedj, -1.28; OCOR, -.67; aromatic, -.lo; C1, .03; Br, .55; NR,(aliphaticj, --1.31;SR, -.04;SO,, .95 F, 1.30;OMe, 1.43;CI, -.11;Br,-.70;Ph,.12;CN, -.72;i-Pr,-.56; 3. H, 0

MARVIN CHAA.TON

194 Set 8-23

Ref.

12-1

Table 12 H,3.76;C1,2.13;Br,2.23;I,2.31;Me,4.19;Et,4.0;i-PrCH,CH,,4.16; CO,Et, 1.8;Ac, 1.8;NO,, 1.68;PhCHZ,3.69 O H , 5 . 1 a ; H , 2 . 7 1 ; F , 1.40;C1,.73;Br, .80;NO,, -3.0 OH, 6 . 5 b ; H , 5 . 1 8 ; F , 3.30;Cl. 3.08;Br, 3 . 1 0 ; N 0 2 , -.5 H, 4.00;CH2CH,-i-Pr, 5.13; Bz; 2.17; trans-2-MeVn, 4.8;Ph, 4.35; PhCH,, 4.9 Me,4.42;H,4.25;Cl, 3.45;C02Et, 3.08;COZH,2.21;2-furyl,4.11; Ph, 3.88;Br, 3.32; I, 3.42 H, 5.5; PhS, 5.93; PhSO, 4.10; I’hSO,, 3.69; Ph, 5.38 H. 4.65; Me, 4.30; PI, 4.44; Ph, 3.62; CI, 3.05 Me, 4.07; Ph, 3.57; H, 3.32; CO,Me, 2.8 H,4.44;Ph,4.5;Cl, 3.56;1, 3.39;PhCHZ,4.11 H,5.77;Me,6.16;Br,4.78;CI, 4.94 H, 5.55; Me, 5.99; C1, 4.79; Br, 4.64; I, 4.49 Me,5.12;Et,5.13;H,4.693;CI, 3.91;Br, 3.74;1,3.77 H, 20.0; Me, 3.87; C1, 3.40; Br, 3.82; I, 1.62

12-2 12-3 12-4 12-5 12-6 12-7 12-8 12-9 12-10 12-11 12-12 12-13 12-14 12-15 12-16 12-17 12-18 12-19

12-20 12-2 1 12-22 12-23 12-24 12-25 12-26 12-27 12-28 12-29 12-30 15-1 15-2

”

Data F , 258.71; CI, 316.22; Br, 350. 21; I, 387.39; OMe, 232.7; SMe, 304.5; CN, 346.2;CHO, 376.87;H, 318.5

H,41.l;Me,2.36;C1,36.5;Br,23.1;1,15.0 H, 1.32; Me, ,437; C1, 2.32; Br, 3.09; I, 2.68 H, .447;Me, ,125; C1, .920;Br, 1.31; I , 1.14 H, .230;Me, .0401;C1, .646;Br, .976; I, .909 H, 1735;Me, 1728;C1,1742.5;Br, 1740.5;1, 1739.5 H, 0; alkyl, -.26; cycloalkyl, -.33; C H 2 0 , -.02; CH,I, -.02; CH,S, -.15; CH,Cl, .12; CH,Br, .12; CN, .78;CO, 1 . 1 3 ; C 0 2 H , 1.35; CO,R, 1.15;CHO, .97;NCO, .93;COCl, 1.41;OR(aliphatic), -1.06; OR(conjugated), --.65; OCOR, -.40; aromatic, .37; C1, .19; Br, .40; NR,(aliphatic), -1.19;SR, -.24;SO,, 1.15 F , .96;OMe, 1.29;CI, -.19;Br, -.55;Ph. -.38;CN. -.58;i-Pr, .48; H, 0 F,281.65;Cl, 324.20;Br, 345.10;1, 371.36;OMe, 241.8;SMe, 290.4; CN, 358.0; CHO, 367.62; H, 31 8.5 Me, .37;H,O;Ph, -.38;Br, -.585;CI, -.19;CO,Me, -.89;Ac, -.76; CN, -.58;NO,, -1.22 H, -1.16;C02Me, -2.24;Me, -.62;Ph, --1.37;Br, -1.29 H, -.97;CO,Me, -1.98;Me,-.55;Ph, -.87;C1, -.99 H, -1.36;CO2Me, -2.23;Ac, --2.12; Me, -.91;C1, -1.21;Br, -1.55; Ph, -1.66;CN, -1.99;CHO, -2.lO;COCl, -2.47;NOZ, -2.59 H, -.40;CO,Me, -1.54;Ac, -1.43;Me, .08;C1, -.51;Br, -.75;Ph, -.91;CN, -1.35;CHO, -1.46: COC1, -1.86;NOZ, -1.89 CN, -256.5;C1, -234.8; Br, -241.5;Me, -216.3 H, -.66;Me, -.43;C1, -.83;Br, -1.15;COZMe, -1.41;Ac, -1.24; COCI, -1.63; Ph, -.98 H, -.95;CO,Me, -1.61;Me, -.68;Ph, -1.32 H, -416.74;AcO. - 4 0 4 . 9 5 ; 0 1 ~ ,-368.97;OMe, -372.60; MeS, -396.46; Me, -408.68; Ph, -423.53; C1, -435.39; Br, -453.04 Table 15 CO,H, .09;CHO, .19;CH,OH, 5.17;Et,62.2;Me,29.2 ” Me, .57;H, .71;C1, 1.20;NOZ,5.51;CN,4.11;Ac, 1.21;MeO, .18; F, .85; Br, 2.11; I, 1.95; CO,M:, .72

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 195 Set 15-3 15-4 15-5 15-6

15-7 15-8 15-9 15-10 15-11 15-12 15-13 15-14 15-15 15-16 15-17 15-18 15-19 15-20 15-21 15-22 15-23 15-24 15-25 15-26 15-27 15-28 15-29 15-30

Ref.

Data H, .71; Me, .41;C1, 10.27;Br, 6.66; I, 3.62 NO,, 2.32; CN, 2.55;Ac, 2.73; MeO,C, 2.78; F, 2.86;Cl, 2.80; Br, 2.79; I, 2.82; Ph, 2.90; H, 2.98; Me, 3.02; MeO, 3.12; Me,N, 3.35 CHCl,, .60; Br, .28; SO,H, .11; CO,Et, .056; CO,H, .18; CCl,, .006; SO,Me, .0001;CN, .0001 Me, 2.0; H, l.O;CH,F, 3.4 x lO-’;CH,Cl, 1.9 x lO-,;CH,Br, , X ~ O - ~ ; 1.3 x lO-’;CH,CN, 2.7 x 10-3;CHCl,, 2.6 x 1 0 - 5 ; B ~1.3 CCI,, 2.9 x lo-’ Bz, 61;Br, 30; 3-O,NC6H,, 15;CO,Me, lO;CO,H, 4.9;CHO, 1.8; CN, .022; NO,, .020 CO,Et, 1.06 x lo-’, CH,CN, 440; H, 3.9 x 10’; Me, 4.5 x lo6; CH,NMe:Br-, 2.84 x lo-’ CO,Et, 6.7 x 10-’;CH,NMe+J3r-, 9.1 x lo-’; CH,CN, 100; H, 2 x lo4; CH,OH, 6.9 x l o 4 ;Me, 3.2 x l o 5 CO,Et, CO,Et, 3.4 x lO-’;CO,Et,Me, 2.76;C1,CHZOH,3.08; Ph,CH,NMelBr-, 37; CO,Et,F%, 220 CO,Et,CO,Et, 3.7 x 10-‘;CO2Et,Me, 1.04;CI,CH20H, .31;Ph, CH,NMeiBr-, 4.8; CO,Et,Ph, 2.3 Ph, 11,00O;Bu, 2,000; H, 84;CH,OAc, 10;CH,OBz, 14;CH,CI, 1.6; CH,Br, l.O;CH,CN, .23; Br, .0011; CO,Et, .004 CH,Cl,77;Ph, 18;Br,O.ll;CO,H,O.l9;H, 11,000 H, 1.481, Et, 3.462; F’I, 3.320; Bu, 3.299; S-Bu, 2.966; CH,-I-Bu, 2.539; OEt, 8.54; OAc, 3.36 CH,OBz, 9;CH,Cl, 3.8;CH2Br,2.2;Br, .012;CO,H, .44 CH,Cl, 16; Ph, 8; Br, .07;CN, 4.0; NO,, 1.0 H, l;CH,Cl, l;CH,OMe, 30;Ph, 5000; Me, 8000;Et, 10,000; I-Bu, 8000 H,4.81;F, 340;C1, 1.70;Br, .395 H, 5100; Me, 100,000; Et, 80,000; CH,OH, 1120; CH,CH,OH, 8400; MeCHOH,CH,, 6100; CH,Cl, 11; CH,CN, 4.3 Et, 1.195; Ph, .6021; PhCH,, .9542;CICH,, .1761; Me,Si, ,3076; F3C, -.4543; ClCH,CH,, .6585; EtO,CCH,, .6886 CONH,, 2.00; CO’Me, 46.0; CN, 13.7; SO,Me, 90.0 CONH,, 6.30; PO(OCH,CH,Cl),, 20.9;CO2Me, 182;CN, 50.0; SO,Me, 306; Ac, 4000 CONH,, 16.9; CO,Me, 528; CN, 203; SO,Me, 1120 CONH,, 3.50; PO(OCH,CH,Cl),, 10.7;CO2Me, 111;CN, 35.3; Ac, 2280 Ac, 26.4; EtSO,, 2.46; CN, .732;CO,Me, .21; EtCO, 14.1 PO(OEt),, 1.43;CONH2,3.57;CN, 56.8;C02Me, 104;Ts, 755; CO,Ph, 1410; Ac, 12,000; CHO, 12,800; Bz, 40,500 PO(OEt),, .233; CONH,, S61; CN, 14.4; CO,Me, 32.8; Ts, 187; Ac, 3770; CHO, 6490; Bz, 20,800 PO(OEt),, 33.1;CONH2, 65.1;CN, 106;CO,Me, 162;Ts, 1200; CO,Ph, 2270; Ac, 23,300; CHO, 17,000; Bz, 49,200 Ac, 1900;CO,Me, 1030; CN, 1730; Me, 21.9; Ph, 790; H, 34; OEt, 8 ; Vi, 104Sa; OAc, 37 CO,Me, 1440; CN, 2120; H, 21.9; Me, 35.6; Ph, 86

MARVIN CHARTON

196 Set 15-31 15-32 15-33 15-34 15-35 15-36 15-37 15-38 15-39 15-40 15-41 15-42 15-43 15-44 15-45 15-46 1 547 15-48 15-49 15-50 15-51 15-52 15-53 15-54 15-55 15-56 15-57 15-58 15-59 15-60 15-61 15-62 15-63 15-64 15-65

Ref.

Data H, .57; Bu, .56; CH,OAc, .68; OEt, .77; OAc, .80; Ph, 2.26; BuO,C, 2.54; CO,Me, 2.54; CN, 2.93 C,H,,, 1.03;Ph, 2.56;OAc, 1.28;OBu, 1.2O;CN, 3.17 F,7.1;C1,36.7;H, 74.8;Me,92.6;Ph,404;Vi, 371a F,4.9;CI, 18.6;H, 29.2;Me,32.7;Vi,94a Me,H, 108.6; Me,Me, 342.5; F,H, 15.5; F,Me, 51.8; CI,H, 66.8; Vi,H, 434a Me,H,93.0;Me,Me,278;F,H,7.0;F,Me, 31.7;Cl,H, 36.8;Vi,H, 391a Ph, lOO;Vi, 9a;BuCH,CH,, l.O;OAc, .8; PhCH,, .7;CICH,, 0.5; .:H NCCH,, .3;CCI,CH,, .3 H , 23.4;Me, 10.4;Et,9.6;Pr, 7.1;Bu,6.6;C1,40.6 H,H, 23.4;Me,Me,5.7;Me,BuCH,,4.2;CO2Et,CO2Et, 6.30 OAc,H, 3.10;CH20Ac,H,6.17;C0,Me,H, 10.5;Ph,H, 13.8;Ph,Me, 16.6;Me,C02Me,24.0;Me,CN, 33.2 H, 8.0;Me, 46.5;Et,43.5;Br, 23.2;C1,22.7 H,32;Me, 141;Et, 138;Br, 70;C1, 77 H,81;Me, 333;Et, 300;Br, 151;C1,163 F, .0138;C1, .301;Br, .676;H, 1.000;Me, 14.5;Et, 19.7;F,F, ,012; Me,Me, 286 F, .0190;C1, .265;Br, ,622; H, 1.000;Me, 9.20;Et, 14.1;F,F, .015; Me,Me, 151 F, .0242;C1, .235; Br, 5 8 8 ; H, 1.000; Me, 6.41; F,F, .0182;Me,Me, 90.1 F, .000276;Cl, 2.03;Br, 1.86;H, 1.00;Me,4800;Et, 1430;F,F, .000645; Me,Me, 825,000 Ph, 17; BuO, 3.9; CO,Me, 2.04; CH,OH, 1.5; C,H,,, 1.00; PhCH,, .99; OAc, .81; CH,CI, .72; CH,OAc, .59;CH,CN, .37 C,H,, 158; Ph, 123; Ac, 424;CN, 308; CO,Me, 164;C1,7.2; OAc, 2.2; OEt, 1.4; CH,CI, 4.0; CH,OAc, 1.4 CO,Me, 237; CN, 410;CH,Cl, 5.6; CH,OAc, 1.7 Ph,2.9x105;CN,4.8x10S;C0,Me,2.6x104;C1, 1.3x104;OAc, 2.9 x lo3;OEt, 980; CH,OAc, 4900 C,H,, 774; Ph, 821; CN, 286; C1,30; OAc, 19;CH,Cl, 4.3; CH,OAc, 16.8 C,H,,2 x1OS;Ph,5 xl0';CO,Me,2090;C1,232;OAc,279;OEt, 695; CH,OAc, 418 MeO, .89; Me, .48; H, 0; C1, -1.47 MeO, .80; Me, .48; H, 0; C1, -1.40 MeO, .30; Me, 0; MeOCH,, -.55; H, -1.42 MeO; .38; Me, 0; MeOCH,, -.60; H, -1.80 CI, .019; H, .19; Me, .57; Et, 1.15; i-Pr, 2.2; t-Bu, 5.6; OMe, 1.9 CI,CI, .0009; Cl,H, .19; Cl,Me, .12; H,H, -.19; H,Me, .57; Me,Me, 2.0; H,OMe, 1.9 OMe, ,000841; Me, ,000227; Ph, .0000428; H, .0000683 Me,Me, .000336; Me,H, .000154; H,H, .0000683 ;Cl,H, .00000690 Me,Me, 240; Me,H, 15; Me,Cl, 1.5; H,C1, .002 Me, 23.O;Ph, 183;C1, 1.08;CF3, .326;CN, .147;Me,, 36.2 Me, 1.20;Ph, 5.67;C1, .02;CF,, .314;CN, ,055; Me,, 36.2 Me,2.68;Ph, 37.0;C1,2.07;CF3, 19.5;CN,23.2;Me2, 3.43

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 197 Set 15-66 15-67 15-68

15-69 15-70 15-71

15-72 15-73 15-74 15-75 15-76 15-77 15-78 15-79 15-80 15-81 15-82 15-83 15-84 15-85 15-86 15-87 15-88 15-89 15-90 15-91 15-92 18-1 18-2

18-3 184

Ref.

Data Me, 1.15;Ph,9.2;Cl, .309;CF,, 15.9;CN,4.42;MeZ,3.43 PhSO,,PhSO,, .29; Bz,PhSO,, ,727; Bz,Bz, .0384; Ac,Ac, .009; CN,CN, .00328; CO,Me,CO,Me, .00268; CO,Et,CO,Et, ,0024; CO,H,CO,H, .00222; CO,Me,H, .0000622; CN,H, .0000475 PhSO,,PhSO,, ,00656; CN,CN, .00318; Bz,PhSO,, .000258; Bz,Bz, .000257; CO,Me,CO,Me, .0000328; CO,Me,H, .0000622; CN,H, .0000475 PhSO, ,PhSO, , .115 ; PhSO,,Bz, ,0275 ; Bz,Bz, .O136; CN ,CN, .000806; CO,Me,CO,Me, .000724; CO,Me,H, ,0000118; CN,H, .0000104 PhSO,,PhSO,, .00194; CN,CN, ,00091; Bz,Bz, .0000666; CO,Me, CO,Me, .00000628; CO,Me,H, .0000118; CN,H, ,0000104 CN,CN, .0453; CN,CO,Me, .0084; CO,Me,CO,Me, ,00215; CO,Et,CO,Et, .00160; CN,H, .00145; CO,Me,H, .000718; Ph,H, .00007; Ph,CO,Me, .00002; Me,CO,Me, .000005;Me,CN, .000011 CN,CN, .0435; CN,CO,Me, .0042; CN,H, .00145;CO,Me,CO,Me, .0000205; CO,Me,H, ,000718; Ph,H, .0007 CN, .0084; CO,Me, .00215; H, ,000718; Ph, .00002; Me, .000005 CN, .453;CO,Me, .0084; H, .00145; Me, .000011 Bz,Bz, ,0144; PhSO,,PhSO,, .0106; Bz,PhSO,, ,00772; CN,CN, .000224 Bz,Bz, 1.94; PhSO,,PhSO,, 12.8; Bz,PhSO,, 4.13;CN,CN, 19.4 Me,CO,Me, .000148; Me,CN, .000205; CN,H, .00145; CO,Me,H, ,000718; Ph,H, .00007 OBu, .00604; 0-i-Bu, .00598; Ph, ,002; CO,R, .0005; 4-MeC6H,, .0026 Ph, 3.5; CHO, 1.8; CO,Me, 2.0; CO,Et, 1.9;CN, 2.2; Ac, 2.3; NO,, 3.7 CN, ,211; MeO,C, .688;OAc, .945; Br, .730; C1, .879;Ph, 1.60;Me, ,374 CN, .184; MeO,C, .192; OAc, .15 1 ;Br, ,349; CI, .319; Me, 1.82 CO,Et, 9.85; BuO, .40; Ph, .40; BuCH,, .24; CN, 1.07 H, 9.85; CO,Et, 8.36; Me, .27; Ph, ,095 EtO, 29,200; Ph, 105; PI, 101; nC,H,,, 66.6; OAc, 12.9; CH,CO,H, 5.15 EtO,C, 66; BuO, 15;Ph, 9.3; Bu, 2.6 EtO,C, 48;Ph, 1.60; EtO,CCH,CH,, .19; BuCH,, .137; CH,OAc, .46; OBu, .31; Vi, .7a H,48;Ph,2.8;Me, I.OO;Me,N, .27;C02Me,287 , C1,57; CH,CO,Me, 39; H, 48; Me, 17 PhO,C, 2500; EtO,C, 707; CN, 434; Ph, 1.40 CO,Me, 384; Ph, 11.7; AcOCH,, 7.25; MeO,CCH,CH,, 3.75; BuCH,, 2.64; CN, 279; CO,Et, 399 Me,CO,Et, 3.77; Bz,Bz, 327; CN,CN, 166; CO,Et, CO,Et, 72.5 Me,CO,Et, 32.5; Bz,Bz, 2380; CN,CN, 1280; CO,Et,CO,Et, 604 Table 18 Me2N,9.12;NH,, 10.20;Me, 10.21; Et, 9.98;Pr,9.86;Bu, 9.82; F,11.40;H,10.87;OH, 11.05;OMe,10.82;OEt, 10.61 ” Me,N, 8.81;NH2,9.71;CH,C1,9.71;Me,9.69;Et,9.53;Pr,9.39; 10.21;Ac,9.23;OH, 10.35;OMe, Bu,9.17;Cl, 11.02;Br, 10.55;H, 10.27; OEt, 10.10 ” Me, 9.53; Et, 9.32; H, 9.98; OH, 10.24; OMe, 9.87; OEt, 10.00 ” CH,Cl, 10.20; CH,Br, 1O.13;CCl3, 10.44; Me, 10.10; Et, 10.00; H, 10.61

MARVIN CHARTON

198 Set 18-5 18-6 18-7 18-8 21-1 21-2 21-3 214 21-5 21-6 21-7 21-8 21-9 24-1 24-2 24-3 244 24-5 24-6 24-7 24-8 24-9 24-10 24-11 24-12 24-13 24-14 24-15 24-16 24-17 24-18 24-19 24-20 24-21 24-22 24-23 24-24 24-25 24-26 24-27 24-28 24-29 24-30

Ref.

Data CF,,10.25; Me,9.27; F,10.6;C1,10.6; H,10.87;Ph,9.45 ” CF3,11.81;Me,9.69;Et,9.32;Bu,9.l0;CI, 11.78;H, 10.87;Ph,9.45 ” OH.1637;OMe,1631;OEt,1635;C1,1609;H,1618 ” OH,1638;OMe,1639;0Et, 1637;C1,1634;H,1648 Table 21 Me,3.58;OH,3.14769a; OEt,3.25;OMe,3.35;0-, 5.39573b; NH,, 3.717 3.64;PhNH, ’’ Me,4.60; Ph,4.65;OH, 4.52a; OEt,4.52;OMe,4.49; 0-, 5.40b; NH,, 4.54;PhNH,4.701 ” Me,4.67;OH,4.64a; 0-, 5.12b;NH,,4.60 ” Me,4.72; OH,4.74a; OEt,4.60;0-, mb; NH,.4.63 ” i-Pr, 3.05;Ph,2.82;HCNOH,2.55 H,3.00; Me,3.38;Et,3.20; ” OEt,3.66;NH,,3.8788;Et,3.7164;H, 3.43;Me,3.6671;CICH2, 3.38; Ph,3.66 ” Me,2.95;Me,N,3.35;EtO,3.08;EtS,2.94 ” 4-O,NPn, 4.2; ClCH,,4.5;Ph,6.0; 2-PhVn, 6.1;Me,6.6; 4-MeOPn, 6.7;Me0,8.8;EtO,8.95;H2N, 11 ” CICH,,.130; Ph,1.21;2-PhVn, 2.80;Me,7.65;MeO,145;EtO,155; H,N,100 Table 24 MeS,5.85;EtS,6.049;PhS,4.481;MeO,5.68;EtO,6.37;Ph,7.00;A NH,,11.9 Ph,308;Me,198;EtO,CCH,,385;CCl,,770;4-0,NC,H4, 441 Me,157.2;Pr, 123.8;Et,134.5;Ph,97.l;CH2C1,45.7 Me,70.1;PI,52.3;Et,55.1;Ph,40.2;CHZC1, 21.8 Me,126.5; PI,80.4; Et,93.6; Ph,81.8;CH,CI,31.8 Me,51.5;Pr,35.2;Et,38.9;Ph, 37.5;CH2C1, 14.4 Me,59.0;Pr,45.5; Et,44.0;Ph,34.8;CH,Cl,21.0 PI,22.3;Et,20.2;Ph,18.6; CH,Cl,12.0 Me,25.9; Me,41.8;Pr,35.1;Et,33.3;Ph, 30.2;CH2C1, 14.8 Me,18.5;Pr,16.7;Et, 15.4;Ph, 15.4;CHZCl, 8.0 Me,135.0;Pr, 129.1;Et,122.1;Ph,102.6;CH,CI, 47.7 Me,60.1;Pr,50.7;Et,52.6;Ph,40.8;CH,C1,22.1 Me,112.7;Pr, 81.9;Et, 79.4;Ph,84.6;CH2Cl, 32.3 Me,43.7;Pr,35.4;Et,33.0;Ph,34.8;CH,CI,15.8 Me,176.7;PI,112.2; Et,104.8;Ph,106.0;CH,CI,42.5 Et,45.6;Ph,41.5;CH,CI,18.7 Me,71.7;Pr,44.6; 109.0;CH2C1, 31.3 Me,173.7;Et,lOl.O;Ph, Me,78.5;Et,41.8;Ph,44.0;CH2C1, 16.1 Me,134;Et,107;H,64;CH,CI,38;CCl,,32 MeS,3.7;MeO,5.1;Ph,8.1;Me,12.0;Me2N, 16.0 MeS,3.0;Me0,3.8;Ph,6.5;Me,8.7;Me2N, 11.0 MeS,2.5;MeO,2.9;Ph,5.0; Me,6.4;Me,N,7.7 MeS,.93;MeO,.97; Ph,1.48;Me,1.72;Me,N,1.91 MeS,34;MeO,.89; Ph,1.22;Me,1.40;Me,N,1.55 MeS,.77;MeO, .82;Ph, 1.15;Me, 1.21;MeZN, 1.31 Me,6.4;Et, 6.4;H,6.1;CH2C1,4.7;CC1,, 3.8 CF,,3.6;Me2N,6.0;Me, 6.1;Ph, 5.2 OMe,3.3;SMe,3.2;NMeZ,6.1;Me, 3.7 CF,,185;Me,N,338;Me,342;Ph,283 OMe,170;SMe,162;NMe,,342;Me,193 ”

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 199 Set 24-3 1 24-32

Ref.

24-33

”

24-34 24-35 24-36 24-37 24-38 24-39 2440 2441 2442

”

2443 2444 2445 2446 24-47 24-48 27-1 27-2 27-3 274 27-5 2 7-6 30-1 30-2 30-3

30-4 30-5

30-6

”

Data Me,N, 183; EtO, 152; Et, 160; Me, 160; Ac, 87a; Ph, 152 ClCH,, 57; Ac, 4Sa; Bu, 84; t-Bu, 77; Me,N, 123;i-Bu, 77; BuCH,, 77; Ph, 77; EtO, 84; Et, 77; Me, 97 Me,N, 117; 2-MeVn, 97; Ph, 84; Bu, 117; 2-PhVn, 90; 2-furyl,70; i-AmO, 70 Me, 84; ClCH,, 70; EtO,C, 32a, EtO, 49; 2-furyl, 77 Et, 77; MeO, 84; Pro, 70; i-Pro, 74; BuCH,, 84; Me, 77 MeO, 49; C1,35; Et, 84; Ph, 63 Me, 2600; i-PI, 2300; Bu, 2400; ClCH,, 1500; CL,CH, 900; Cl,C, 650 Et,3.9;Me,6.8;H,2.9;CHZCl, 1.3;CC13,.3;Ph, 3.8

”

Et,4.0;Me,3.9;H,3.7;CH,Cl,3.3;CCl3,2.5

” ”

” ” ”

OMe, .52; SMe, .72; Me, .85; NMe,, 6.9 H, 19;Me, 61;Et,2l;Cl, .13;ClCH,, l.l;Cl,CH, .45;OEt, 10.5 ” Et, 16.82; i-PI, 16.37; t-Bu, 13.03; CH,Cl, 12.80; CHCl,,9.35; CCl,, 3.05; Me, 17.08; Pr, 16.76; H, 17.00; EtO, 15.98 ” Et, 3.0 x lo6;i-Pr, 8.8 x l o 5 ;t-Bu, 2.3 x 10,; CH,C1, 4.9 x 10; CCl,, 1.7 ” Me, 27.80; Me,N, 29.64; EtO, 22.37; CF,, 16.58;C1,17.22 ” Me, 16.38; Et, 16.23; MeO, 15.17; t-Bu, 12.83;CF3, 2.7 ” Et, 16.53;i-Pr, 16.16; t-Bu, 14.58; EtO, 16.82;Cl, 3.3;MeO, 16.23 ” Me, 17.03; Et, 17.43; PI, 17.50; i-Pr, 17.07; t-Bu, 16.95; Me,N, 27.80; MeO, 16.38 ” Et, 162;i-P1, 155;t-Bu, 137;CH,C1, 150;CHCl,, 116;CC13,74;Me,160 Table 27 3-PnNO,, 10.16;4-PnNOZ,9.96;4-PnNMe2, 11.25; 2-furyl, 10.85; Ph, 10.68; 3-MeOPn, 10.59; 4-MeOPn, 10.92; 2-PhVn, 10.55; Bz, 8.30; CO;, 10.23 ” Me, 12.42;Ph, 11.35;Ac,9.30;Et, 12.45;Bz,9.25;NOZ,7.4 ” 4-O,NPn, 10.47;Ph, 11.18;H, 11.33;Bz,8.80;Ac, 8.85;CO;, 30.95; CO,Me, 8.87; CO,Et, 8.95; CONH,, 9.55 ” Ph, 11.33; 3C6H4N0,, 10.74; t-PhC,H,, 10.89; 2-f~1yl,11.16; 2-thienyl, 10.76; ~ z C ~ H11.60 ,~, ” H, 8.30; Me,9.30; Et, 9.38; i-Pr,9.50, Ac, 7.38; CO,Et, 1.01 ” 4-O,NPn, 10.85; Ph, 11.18; H, 10.68; Me, 11.35; CO;, 11.63; CONH,, 10.1; Bz, 10 Table 30 Ph, 11.6; MeS, 9.83; Me, 12.41; MeO, 9.72; NH,, 13.86; EtO, 10.021; BuO, 10.146; Pro, 10.155; Me,N, 13.4; CH,=CHCH,O. 9.70 ” H,N, 10.770; PhNH, 10.42; MeO, 7.41;MeS, 7.14 ” OH, 3.90309a; H, 3.7857; Me, 4.7807; Et, 4.8948; Pr, 4.8060; i-Pr, 4.8248; t-Bu, 5.0155; CO;, 3.89963b; CH,Cl, 2.8159; CH,OH, 3.8748; NH,, 5.74 ” OH, 4.108a; Me, 4.7696;Et, 4.8844; PI, 4.8030; AcNHCH,, 3.6816; MeOCH,, 3.5381; NCCH,, 2.44466; H, 3.7719;CO;, 3.9340Sb ” OH, 4.055Sa; Me, 4.7582; Et, 4,8742; Pr, 4.8044; CH,CI, 2.8447; CH,Br, 2.87514; CH,I, 3.1433; CH,AcNH, 3.6726; CH,CN, 2.4523l;CH2OMe, 3.5505; H, 3.7572; CO; 3.95468b; Ph, 4.214 ” H, 1.79 x 10-4;Me, 1.734 x lO-’;Et, 1.32 x IO-’;Pr, 1.53 x lo-’; i-Pr, 1.44xlO-’;Bu, 1.51 xIO-’;i-Bu, 1.70~10-’;r-Bu,9.4 x 1 O V 6 ; truns-2-MeVn, 1.95 x lo-’; ViCH,, 4.8 x CICH,, ICH,, 7.0 x 10-4;Cl,CH, 5.83 x lo-’; 1.49 x lo-’; BrCH,, 1.29 x HOCH,, 1.46 x 6.09 x 1.42 x 1 0 - ~ b ” ”

MARVIN CHARTON

200 Set 30-7

Ref.

30-8

30-9

30-1 0

30-1 1 30-1 2

30-1 3 30-14 30-1 5 30-16 30-1 7 30-1 8 30-1 9 30-20 30-2 1 30-22 30-23 30-24 30-25 30-26 30-27

‘

Data CCI,, .217; Me, 1.753 x IO-’;Et, 1.338 x 10-5;Pr, 1.592 x lo-’; CH,F, 268.4 x IO-’;CH,Cl, 139.4 x 10-5;CH,Br, 129.63 x lo-’; CH,I, 69.46 x IO-’;CH,CN, 346.94 x lo-’; MeOCH,, 27.60 x lo-’; Ph,6.13 xIO-’;H, 17.65 xlO-’;C,H, 1.359 x I O - ~ ; C O ; , 1.134 x H, 3.7515;Me, 4.7560;Et,4.8742;Pr,4.8l96;Vi,4.255;ViCH2, 4.3521;C1CH2, 2.8668; BrCH,, 2.90205; ICH,, 3.1752; HOCH,, 3.8309; PhCH,CH,, 4.6644; PhCH,, 4.3074; Ph, 4.2050; NCCH,, 2.47011;HCZ, 1.84. frans-2-PhVn, 4.438;Me3SiCH,, 5.22;C02H, 1.571 ;CO;, 3.96Sb;’CF,, -.26; OH, 4.06550; NHAcCH,, 3.6698; CH,OMe, 3.570; r-Bu, 5.03; CCl,, .635 OH, 4.1 19a; Me, 4.7570; Et, 4.8775; Pr, 4.8286; CH,Cl, 2.88342; CH,Br, 2.91800; CH,I, 3.1934; CH,CN, 2.481 78; CH,AcNH, 3.6731 ; CH,OMe, 3.5834; H, 3.7525; i-Pr, 4.8857; r-Bu, 5.04048; CO;, 4.00700b; CO,H, 1 .56a OH, 4.0783a; Me, 4.7625; Et, 4.8827; Pr, 4.8419; CH,CI, 2.89983; CH,Br, 2.93599; CH,I, 3.2128; CH,NHAc, 3.6779, CH,CN, 2.49550; CH,OMe, 3.5996; H, 3.7577; CO;, 4.0296Sb; CO,H, 1.57268a OH, 4.0969a; Me, 4.7773; Et, 4.9007; Pr, 4.8706; CH,AcNH, 3.6945; CH,CN, 2.5281 2, CH,OMe, 3.631 3; H, 3.7734; CO;, 4.0872Sb; Ph, 4.241 Me,5.28;t-Bu,5.52;PhCH,,4.79;H,4.21;HOCH,,4.26,ICH,, 3.61; BrCH,, 3.46;C1CH2, 3.33. FCH,, 3.13; NCCH,, 2.94; Ph, 4.71; CO,H, 1 .967a; CO;, 4.49d Ph, 6.63; i-Bu, 7.33; cyclohexyl, 7.47; HOCH,, 5.78; H, 5.61; CH,C1, 5.04; PhCH,, 6.73; I-Bu, 7.76; rrans-2-PhVn, 6.68; PhCH,CH,, 7.03 H, 11.15;PhCH2, 10.34;Ph. 10.43;CH,C12,7.28 H, 8.92; Me, 10.57; ClCH,, 8.48; CH,CH, 7.07; CI,C, 5.32; Ph, 10.92 H,9.02;Me, 10.68;C1CH2,8.60;CI,CH, 7.19;C13C, 6.04;Et, 10.89; Ph, 11.34 CHCI,, 2.60;CHZCI,4.74; Ph, 6.27;Et, 7.18; r-Bu, 7.43 CCl,, 1 .OO;CHCl,, 2.00; CH,CI, 3.97; H, 4.74 CCI,, .443;CI,CH, :016;CH2C1, 9.0 x 10-4;Me, 3.3 x H, 9.2 x lO-’;Ph, 5.8 x CCI,, 2.26; CHCI,, 2.54; CH,CI, 4.54; H, 5.05; Me, 5.85 H, 8.64;Me, 10.03;C1CH2,8.31;C1,CH, 7.41;C13C,6.26,Et, 10.07; Ph, 9.79 CI,C, .70;CHCI,, 1.75;CH2C1, 2.80;H, 3.64;Ph,4.58;Me, 5.18 t-Bu, 112; Bu, 83; i-Bu, 70; Et, 43; Me, 20; PhCH,, 16; CICH,CH,, 1.8; ClCH,, .14; Ph, 52 r-Bu, .30103; Et, .32; Me, .38; PhCH,, .45; HOCH,, .75; H, .66; Lh CH,CI, .83 I-Bu, 1.497;Et, 1.449;Me, 1.423;PhCHZ,1.30103;Ph, 1.182; HOCH,, 1.137; H, 1.217;CH2C1, .73;CH,CN, .58 CCI,, 11.0;CHCl,,4.07;NCCH,, 2.77;C1CH2, 2.12; H, 1.06;Ph, 1.80;Me, 1.06;r-Bu, 1.11 Me, -3.28;CICHaCH,, -2.63; H, -2.29; CH,Cl, -1.62, CHCI,, -.21, CCI,, .I76

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS Set 30-28 30-29

33-1 33-2 33-3 3 3-4 3 3-5 3 3-6 33-7 33-8 33-9 33-10

33-1 1 33-1 2 33-1 3 33-14 33-15 33-16 33-1 7 33-1 8 33-1 9 33-20 33-21 33-22 33-23 33-24

33-25

Ref.

201

Data

Me, 4.26; Ph, 5.43; CH,C1, 47.6; CHCl,, 190; CCl,, 501 NCCH,, 18.5; CICH,, 12.9; HOCH,, 3.01; H, 2.23; ClCH,CH,, 2.24; PhCH,, 1.47; PhCH,CH,, 1.09; Ph, .96; Me, .463; BuCH,, .442; t-Bu, .296 Table 33 Br, O;CI, .44;F, .75;Me, -.75;CF,, 2.36;CN, 3.6;Ph, -.84; t-Bu, -.661; H, 0 Br, .86;CI, 1.1 1 ; I, .55; H, .72; CO,H, 2.31; CHO, 3.39; CO,Et, 2.21; CN,4.55;Ph,O;Vi,.27;Ac, 3.26 H, -.88; C1, I .24; Br, 1.07; 1, .76; CN, 4.24; Ac, 3.2 H, .87;C1, 1.28;Br, 1.06;1, .81;CN,4.25;Ac,3.2 I, 4.59; Br, 3.88; H, 3.6; Ph, 4.55; Bu, 4.24; BuCH,, 4.25 ?-Bus, 910; MeO, 63; t-Bu, 2.1; ViS, 4000 t-Bus, 64; MeO, 15; t-Bu, .8; ViS, 430; ViO, 60 Ph, 6.6; H, 4.8; Bu, .38; MeO, 13: Ph,Si, 450 BrCH,, 430; ClCH,, 390; ICH,, 265; Ph, 250; Me,Si, 66; PhCH,, 25; i-F'r, J2.3;n-Bu, 9.7; BuCH,CH,, 9.4; t-Bu, 8.9; neopentyl, 7.0 ClCH,, 3318; 4-MeOPn, 3323; Ph, 3323; 4-02NPn, 3319; Bz, 3306; EtO,C, 3310; EtO, 3339; BrCH,, 3316; BuCH,CH,, 3319 ClCH,, 3317;Ph, 3320; Bz, 3304; EtO,C, 3309;BrCH,, 3315; BuCH,CH,, 3317 CICH,, 3250; Ph, 3250; Bz, 3219; EtO,C, 3320; BrCH,, 3250; BuCH,CH,, 3267 Bu, 74;Ph,91;C1CH2,94;Me0, 81;EtO,C, 123;BrCH,,94;BuCH2, 74; BuCH,CH,, 72 Bu, 3314;Ph, 3314;ClCH,, 3314;MeO, 3328;EtO,C, 3306;BrCH,, 3313;BuCH,, 3314;BuCH,CH,, 3314;CN, 3304 ClCH,, 3.90; BrCH,, 3.45; EtS, 4.20; MeOCH,, 3.90; EtOCH,, 3.30; BuCH,, 3.90; CN, 6.60 ClCH,, 4.80; BrCH,, 4.50; EtS, 5.70; MeOCH,, 4.50;EtOCH2, 4.20; BuCH,, 4.65; CN, 7.80 CICH,, 6.90; BrCH,, 6.60; EtS, 7.80; MeOCH,, 6.00; EtOCH,, 5.70; BuCH,, 6.30; CN, 10.5 CICH,, 24.60; BrCH,, 24.20; Et, 24.60; MeOCH,, 20.70; EtOCH,, 20.40; BuCH,, 18.60; CN, 43.6 CICH,, 24.30; BrCH,, 24.30; EtS, 22.20; MeOCH,, 20.70; EtOCH,, 19.50; BuCH,, 17.40; CN, 46.6 CICH,, 21.60;BrCHZ, 21.60;EtS, 21.60; MeOCH,, 19.80;EtOCHZ, 19.50;BuCH2, 17.10;CN, 35.8 ClCH,, 34.20; BrCH,, 33.60; EtS, 34.80; MeOCH,, 30.30; EtOCH,, 29.15; BuCH,, 27.10 ClCH,, 46.85; BrCH,, 46.20;EtS, 40.20; MeOCH,, 34.50; EtOCH,, 32.45; BuCH,, 28.50 CiCH,, 47.05; BrCH,, 46.10; EtS, 47.10; MeOCH,, 37.25; EtOCH,, 36.95; BuCH,, 35.70 Me, -1.76;Pr, -1.79;Bu, -1.73;CHO, -1.89;CH2OH, -2.33; CH,I, -2.19; CH,Br, -2.33; CH,CI, -2.40, Vi, -2.92; Ph, -2.93; EtS, -2.64; EtO, -1.33 H, 1S O ;Me, 1.56; Et, 1.59; HC,, I .48; Pr, 1.72; I-Bu, 1.75; CHO, 2.75; Ac, 3.00

MARVIN CHARTON

20 2 Set 33-26 33-27 33-28 33-29 36-1 36-2 36-3 36 4 36-5 36-6 36-7

36-8 36-9 36-10 36-11 36-12 36-13 39-1 39-2 39-3 39-4 39-5 39-6 39-7 39-8 39-9 39-10 39-1 1 39-1 2 39-13 39-14 42-1

Ref.

Data Me, 1.76;Et, 1.78;HC2,2.01;Pr, 1.75;t-Bu, 1.87;CHO,3.28;Ac, 3.03 ” H, 12.97;Me,2.423;Cl, 14.28;Br, 13.96;Et,2.49;Bu,2.50;t-Bu,2.21; Ph, 5.88;COZH,35.3Sa; CO;, 7.10b ” H, 4.68; Me, S68; C0;,2.40; CO,Et, 34Sa ” H, 18; Bz, 135; CO,Et, 99; Ph, 3.0; Me, 1.9 Table 36 H,2.986;Me, 392;CI,2dO;CN,O;Br, 2.94;F, 1.68;1, 3.71;CC13, 1.93;C2H,3.6; t-Bu, 3.65;Ph,4.14 ” Et, 2265.0; i-Pr, 2264; t-Bu, 2254; CICH,, 2266.0; Me, 2267.0; Br, 2196.0 ” Me, 2252.5; Et, 2247.2; i-Pr, 2245.3; t-Bu, 2234.5;CICH2, 2260.4; Br, 2185.1 ” Me, 2255.0; Et, 2249.2; iPr, 2247.4; t-Bu, 2235.8;C1CH2, 2260.4; Br, 2188.4; I, 2168.1 ” Me, 2255.4; Et, 2249.6; iPr, 2247.8; t-Bu, 2236.6; CICH,, 2260.7; Br, 2187.8; I, 2168.2 ” Me, 2255.7;Et, 2249.9;i-Pr, 2246.5;t-Bu, 2235.3;C1CH2, 2261.4;Br, 2188.5; I, 2166.6 ” t-Bu, 169; PI, 167;iPr, 166; Bu, 165; Et, 165; Me,Si, 165; truns-2-PhVn, 165; Me, 159; PhCH,, 158; ViCH,, 155; Ph,C, 155; Ph,CH, 154; Ph, 153;Vi, 143;PhC,, 123;C1CH2,ll7;1,114;Br, 102;CI,CH, 84;Cl,C, 62 ” t-Bu, 85; Pr, 82; i-Pr, 84; Bu, 85; Et, 81 ; trans-2-PhVn, 82; Me, 78; PhCH,, 78;ViCH,, 74;Ph,CH, 74;Ph, 73;Vi,68;C1CH2, 51 ” Me, 160;Pr, 164;Vi, 145;Br, 102;ViCH,, 150 ” Me, 18.2;CICH2,4.38;C1,CH, l.lS;Cl,C, .49 ” Me, 12.4; CICH,, 3.55;CI2CH, .82; CI,C, .39 ” Me, 8.39;CICH1, 2.41;CI2CH, .69;C13C, .20 ” Me, 4.58. CICH,, 1.23;Cl2CH, .46;C13C, .15 Table39 Ph,.49;Ac,2.84;H,O;Et,-.18;CI,1.76;CN,3.76;Pr,-.75;Br, 1.69 Me,9.88;Cl, 10.10;CN, 11.2;H, 10.23 ” ” CN, 1.624; COCI, 1.624; CO,H, 1.626;C02Et,1.627; Bz, 1.628; Ac, I .628; NH,, 1.632; H, 1.6345; Ph, 1.635; CH,OH, 1.637; PhCH,, 1.638; Bu, 1.639; Et, 1.639 ” CN, 1.625; CO,Me, 1.628;CO,Et, 1.627; Ac, 1.629; COCl, 1.624; CH,OH, 1.638; Ph, 1.634; CHi4, I .690 ’’ CN, 2.216;C02Me, 2.224;CO1Et, 2.221; Ac, 2.226;COCI, 2.219; CH,OH, 2.228; Bz, 2.225; r>-CH,, 2.231 w CN, 1.626; COCl, 1.627;CO,H, 1.628; CO,Et, 1.629; Bz, 1.629; NH,, 1.633; H, 1.635; Ph, 1.636 ” CN, 1.632; Bz, I .636; CH,OH, 1.644; Me, 1.647 ” H,4.83;CI, 3.26;COZH,2.12”,CO;, 5.13b ” Ph, 4.50; cyclohexyl, 4.79; CO, H, 3.9Sa; CO,, 4.83b; PI,, 5.04; Ph,, 4.51; Ph, Me, 4.73; H, 4.83 ” i-Bu, 7.90;Ph, 7.42; Gi-Pr, 7.55;CO;, 7.77b; CO,H, 6.3Ia ” H, H, 4.30; Me,H, 47.5; Me,Me, 533; EtO,H, 4030 ” H, .026; cyclopropyl, 191; Vi, 30.8; Et, 9.40 ” Me,C=CH, 8.09; i-Bu, 8.24; Ph, 8.1 1; i-Pro, 8.30 ” H. .026; cyclourouyl. 9.87;.~Vi. 2.67;. Et.. .464 Table 42 Ph, 193.; Vi, 184; CHiCl, 164; CH,Br, 171;Me, 220; Mea, 257 ”

SUBSTITUENT EFFECTS IN NONAROMATIC UNSATURATED SYSTEMS 203 Set 42-2 45-1 45-2 45-3 45-4 45-5 45-6 45-7 45-8 45-9 45-10 45-1 1 45-12 45-1 3 45-14

Ref.

Data Ph, 2.9; Vi, 3.9; CH,Cl, 2.0; CH,Br, 2.2; Me, 5 . 5 ; Me,, 13.0 Table45 H, 10.5;CO,NH,,9.3;CN,7.35;NO,,7.0 H, 11.70; Me, 12.01; C1, 9.87; I, 9.93; Br, 10.03; NO,, 7.97 H, 11.70;Me, 12.59;C1,10.40;Br, 10.42;N01, 8.52 Br, .715 1;C1, .7125; H, .6990; Me, .6454 H, .699;Me, .645;C1, .713;OH, S96; Br, .714 H, 696; Me, .641; C1, .710; OH, 593; Br, .7 10 H, 703.5; C1,721 ;Me, 640.5; Et, 636; Vi, 667 ”

H,-.Sl;Me,-.58;Ph,-.50;C1,-.34 H,-1.14;Me, -1.lO;Ph,-1.03;C1,-.92 H, .711;C1, ,734; Br, .737; I , .737; Me, .653;Et, .650;OH, .600;MeO, ,642; Ph, .698 Me,Me, .5093; Cl,CI, .7230; Br,Br, .7228; Cl,Me, .6542; Br,Me, .6564 Me,Me, .600; Cl,Cl, .740; MeO,MeO, ,476; EtO,EtO, .479 H,H, .71 I ; Me,Me, S97; Me,i-Pr, .589;Cl,Cl, .734;MeO,MeO, .459; EtO,EtO, .479 H,H, -.57; Me,Me, -.67; Cl,Cl, -.18; f-Bu,t-Bu, -.71; SiMe,,SiMe,, -.51

45-15 45-1 6 45-1 7

45-1 8 45-19 45-20 45-21 45-22 45-23 45-24 45-25 45-26 45-27 45-28 45-29

45-30 45-3 1 45-32 45-33 45-34 45-35

H,H, .71 I ; Cl,Cl, .746; Br,Br, .768; Me,Me, .604; Me,i-Pr, S97; PhO,PhO, .633; Ph,Ph, .689 H,H, .711; Me,Me, .607; MeO,MeO, .612; Cl,Cl, .740;Br,Br, .744; I,I, .746 H,H,H,H, -.31; Br,Br,Br,Br, -.16; CI,CI,Cl,CI, -.ll;CI,CI,CN,CN, .25 H,H,H,H, .711; Me,Me,Me,Me, .466; CI,CI,CI,Cl, .703; OH,CI,OH,CI, .422; OH,Br,OH,Br, .418 H,H,H,H, 703.5; Cl,Cl,CI,Cl, 716.0; Cl,Me,Me,Cl, 615.0; Me,Me,Me,Me, 462.8 H,H,H.H, - 5 1 ;Cl,Cl,Cl,Cl, .01;Br,Br,Br,Br, .OO;Cl,Cl,CN,CN, .51; F,F,F,F, -.04; Me,Me,Me,Me, -.84 H,H,H,H, -I.l4;Cl,Cl,Cl,Cl, -.71; Br,Br,Br,Br, -.72; Cl,Cl,CN,CN, -.30; Me,Me,Me,Me, -1.45 H, 235; Me, 190; C1,285; Br, 280 C1, -271; H, -222; Et, -203; NHAc, -199; Me, -190; OMe, -159; OEt, -153; NMe,, -1 10; NH,, -58;OH, 62; CH,OH, -219 H, -222; NHAc, -390; Me, -341; NH,, -305; OMe, -287 H, 795; Me, 748; C1,804, MeO, 741; BzO, 796 H, 741; CO,H, 822; CHO, 807; Ac, 797 H, 710; Me, 658; C1,705; Br, 720 Me,Me, 710;H,H, 795;CI,Cl, 813;CN,CN, 903 H, 795; Me, 753; C1,801; f-Bu, 732; Ph, 778; HO,C, 833; MeO,C, 869; CHO, 872; Ac, 857; NO,, 891; MeO, 676; BzO, 803; MeO,CC,H,, 807; EtO,CC,H,, 808; HOCH,C,H,, 752 H, .833;C1, .810; Br, .810;Me, .796 C1,738; ViCH,, 696; Ac, 821; CHO, 839; CO,Me, 820; CO,H, 779; H, 741; MeOCC,H,, 754; EtO,CC,H,, 758 Me,Me, 710; CI,Me, 765; H,H, 795; CI,Cl, 824 MeO,MeO, 735; Cl,CI, 818; Me,Me, 718; H,H, 795 H,H,H,H, 795; Me,Me,Me,Me, 627; Cl,CI,CI,Cl, 830; Br,Br,Br,Br, 814 H, -124; OH, -294; MeO, -249; Me, -205;C1, -112; NH,, -345; PhNH, -323

MARVIN CHARTON

204 Set 45-36 45-37 45-38

Ref.

45-39 45-40 45-41 45-42 45-43 45-44 45-45 45-46 45-47 45-48 45-49 45-50 45-5 1 45-52 45-53 a

Data H, -278; Me, -346; MeO, -398; NH,, -493; PhNH, -475 H, 488; Me, 422; Et, 419; OH, 362; OMe, 369 H, -4839;OAc, ,4750; NHAc, .4165; Me, .4080;Ph, .4515; NHPh, .2858 OH, -342;OAC, -167;C1, -120;H, -112, NH,, -350;PhNH, -245; AcNH, - 135 OAC, -320; NH,, -505; PhNH, -395; AcNH, -284 C1, -342; OH, -332; NH,, -383; H, -294; PhNH, -324 NH,, .339; MeO, .447; Me, S 4 6 ; NHAc, .560;Ph, .595 NH,, .290; MeO, .440; Me, S50;NHAc, S O ; Ph, .610; C1, .620; CN, .640; CO,H, .600 H, .920; Me, 3 7 5 ; OMe, .809; C1, .927 H, .937; Me, .892;OMe, ,820; C1, .943 H, .9456; Me, .8604;OMe, 3992; C1, 1.006 H, .9255;Me, .8422;OMe, .8737;C1, .9832 H, .9155; Me, .8328;OMe, .8538; C1, .9707 H,H,H,H, 1635; Me,Me,Me,Me, 1637;t-Bu,t-Bu,t-Bu, t-Bu, 1634; Cl,Cl,Cl,Cl, 1646 H, 1675; Me, 1670; Ph, 1667; MeO, 1660; OH, 1663; NH,, 1640; C1; 1684; Br, 1686; NHAc, 1666 Me, 12.42;Et, 12.60;Ph, 11.18;Ac, 7.38;CF3,6.0 H, 9.02;Cl. 2.94; Me, 10.72;NH2, 10.62;Et, 10.67; Pr, 10.81; 2-furyl, 9.80 CO,H, 4.00a; CO;; 4.36b; Me, 4.62; Ph, 4.427

Includes a statistical factor of 1/2. Includes a statistical factor of 2.

Vinyl and Allenyl Cations Peter J . Stang Chemistry Department. The University of Utah Salt Lake City. Utah 84112

CONTENTS I . Introduction . . . . . . . . . . . . . . . . . . I1. Electrophilic Additions to Multiple Bonds . . . . . . . . A . Addition to Triple Bonds . . . . . . . . . . . . 1 . AcidCatalyzed Hydration of Alkynyl Ethers and Thioethers . 2 . Electrophilic Additions to Arylacetylenes . . . . . . 3. Electrophilic Additions to Alkylacetylenes and Acetylene . . B . Electrophilic Additions to Allenes . . . . . . . . . 1. Addition to Allene . . . . . . . . . . . . . 2 . Addition t o Substituted Allenes . . . . . . . . . 111. Vinyl Cations by Multiple-Bond Participation in Solvolysis . . . A . Participation b y Triple Bonds . . . . . . . . . . . B . Participation by Allenyl Bonds . . . . . . . . . . IV. Heterolytic Cleavage of Vinyl Substrates . . . . . . . . A . Vinyl Cations via Diazonium Ions . . . . . . . . . B . Solvolysisof Aryl-SubstitutedVinylSubstrates . . . . . . C . Vinyl-or Cyclopropyl-Substituted VinylSystems . . . . . D . Solvolysis of Simple Alkylvinyl Systems . . . . . . . . E . Structure of Vinyl Cations . . . . . . . . . . . . 1. Theoretical Calculations . . . . . . . . . . . 2 . Experimental Approaches . . . . . . . . . . . F . Rearrangements of Vinyl Cations . . . . . . . . . . 1. Rearrangements to the Double Bond . . . . . . . . 2 . Rearrangements Across the Double Bond . . . . . . G . Kinetic Deuterium Isotope Effects . . . . . . . . . V . Allenyl and Related Cations . . . . . . . . . . . . VI . Miscellaneous . . . . . . . . . . . . . . . . VII . Conclusion and Future Developments . . . . . . . . . References . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

205 207 207 207 210 215 220 220 221 229 229 237 242 254 257 264 269 271 272 274 280 281 284 291 295 311 316 318

I . INTRODUCTION Vinyl cations. la. are carbonium ions where the electron-deficient carbon is part of an unsaturation. with the formally positive carbon bonded to only two substituents. as compared to trisubstituted normal carbonium ions. I b . Although 205

PETER J. STANG

206

ordinary carbonium ions have been known since about the turn of the century (I), vinyl cations have been regarded as unattractive reaction intermediates because of their alleged high energy, and it has been only in the past dozen years that good evidence has been presented favoring the intermediacy of vinyl cations in certain reactions. This chapter will provide a historical and critical review of vinyl and allenyl cation chemistry with emphasis on a mechanistic point of view. >C

=

>"

c"-

Ib

la

A limited amount of information is available on vinyl cations in the gas phase. These mass spectral data suggest that the heat of formation and stability is in between of simple alkylvinyl cations, such as CH2=8H and CH,CH=&, those of methyl and ethyl cations (2). The bulk of the evidence for the existence of vinyl cations comes from mechanistic studies in the liquid phase. Although vinyl cations have not yet been prepared in solution with lifetimes adequate for direct spectral observation, sufficient, increasing evidence has been presented for the existence of such species as transient intermediates. Vinyl cations have been generated in three ways: 1. via electrophilic addition to multiple bonds; a,

R-C=C-R

+Yo

-

0

y,

R-C=C,

-----+

R

2 . via multiple bond participation in solvolysis; RC=CCH,CH,-X

RCH=C=CHCH,CH,X

/

RZPC~

',A -

3. via bond heterolysis in vinyl substrates.

Each of these reactions will be discussed in a separate section (11-IV). Section V will deal with allenyl cations, and Section VII will provide a brief summary and a glimpse at possible future developments.

201

VINYL AND ALLENYL CATIONS

11. ELECTROPHILIC ADDITIONS TO MULTIPLE BONDS

A. Addition to Triple Bonds

1. Acid-catalyzed hydration of alkynyl ethers and thioethers The earliest evidence for vinyl cations as intermediates comes from thorough studies by Jacobs and co-workers and Drenth and co-workers of the acid catalyzed hydration of alkynyl ethers (3-7) and thioethers (8-10). In particular, the hydration of the following compounds has been investigated: RO-Ce-H 2

Et0-M-R 3

RS- C g -H

R = a, n-Bu b , Ph c, Et d, Me e, n-Pr f, i-Pr g, t-Bu

R=a,Me b, Et c, i-Pr d, n-Bu

R = a, Et b, i-Pr C, t-Bu

4

EtS-W-R 5

R=a,Me b, Et c, n-Pr d, t-BU e, D

Hydration of compounds 2, 3, 4, 5 was found to be first order both in substrate and in hydronium ion (4-10). Furthermore, a careful kinetic study of compounds 2c-g and the sulfur analog 4 revealed that the hydration rate at constant ionic strength was dependent on the buffer concentration and hence was general acid catalyzed. The solvent deuterium isotope effect for hydration of 4a and lcH20/kD,o= 1.90, CH3C'-C-OCH=CHCH3 were kH,o/kD,o=2.13 and respectively ( 8 , 6 ) . No deuterium was incorporated at the acetylenic position in 4a when this compound was reisolated after partial hydration in Dz0. In all the above compounds except 2f and 2g, hydration gave the corresponding ester or thioester as products: 0 II

R-Cg-X-R'

+ H,O + RCH,C-X-R'

X=OorS

These data were interpreted to indicate the mechanism in Scheme I. The general acid catalysis, the deuterium solvent isotope effects, and the lack of deuterium incorporation upon partial hydration in D20 are particularly convincing evidence for a rate-determining protonation and the discrete intermediacy of a vinyl cation such as 6 . As the alkyl groups R are varied on compounds 2-5, the rates of hydration

PETER J. STANG

208

RCS-X-R'

+ H,O'

H \

%

x=o.s

e

R

\

/ R H \

e

C=C-X-R' + H,O

\

fast

--+

@OH, I

/C=C-x-R' R @OH, I C=C-X-R'

/

H

YH CS-X-R'

/ R

\

+ H,O +

R

H,

+ H,O

6

H

H

X-R'

/"="

OH I

C=C-X-R' + H 3 0 e

/

R 0 II

== RCH,C-X-R'

Scheme I. Mechanism of Hydration of Alkynyl Ethers and Thioethers.

follow the Taft relation (1 l), with p* = -6.6 for 2 (4, 7), p * = -2.57 for 3 (13), = -.73 for 4 (9), and p* = -3.76 for 5 (9). The large negative rho values are in accord with the proposed electrophilic attack by a proton in the ratedetermining step. The magnitude of the rho value in 2 relative to that in 4 suggests that oxygen is a much better transmitter of polar effects than is sulfur. In the hydration of compounds 2f and 2g, besides the expected ester, three other products (acetic acid, an alkene, and alcohol) were observed. These products were postulated to arise via a fragmentation of the intermediate vinyl cation, 6, as shown in Scheme 11. The importance of the fragmentation path is presumably determined by the stability of the alkyl cation formed by the alkyl oxygen fission. Product studies, general acid catalysis, and kinetic data indicate that hydration of compounds I and 8 also proceed by way of a vinyl cation (12, 13). p*

R

Et-X-CEC-C-

I I

R

7,X=S a,R=Me 8 , X = 0 b, R = Et

OH

However, the rates of hydration of these compounds are about a factor of ten to one hundred faster than predicted by means of the Taft relation. Anchimeric assistance by the hydroxyl group in the transition state for protonation, 9, has

VINYL AND ALLENYL CATIONS

209

CH, CH3 CH3 I H” @ I Q I H C g - 0 - C - R ---t H,C=C-0-C-R * H,C=C=O-C-R I VI CH3

1

R = H, CH, cH3/

7H3 H2C=C-O-C-R I I @OH, CH,

I1

hH36

\H,O

0II 7H3 CH,C-0-C-R I CH3

YH3

+

HzC=C=O

R-CQ I

O..\“../

0 II CH,C-OH

yI3

( 7 3

R-C

II

CHZ

R-C-OH I CH3

Scheme 11. Mechanism of Hydration of 2f and 2g.

been suggested as an explanation of this discrepancy (12, 13).

Clearly, a large body of diverse evidence indicates that the acid-catalyzed hydration of alkynyl ethers and thioethers proceeds via a rate-determining protonation through a vinyl cation. However, these vinyl cations are unique in that they have a resonance form where the positive charge resides on the el

R-X-C=CHR’

B

+---*

R-X=C=CHR’

heteroatom via delocalization of the lone electron pairs on either oxygen or sulfur. The result is special stability in such ions. The situation is analogous to the behavior of ordinary carbonium ions generated by solvolysis, where a-halo ethers are some lo6 more reactive than unsubstituted halides (14). The importance of such resonance contributions involving the heteroatom also accounts for the lo3 to lo4 times greater reactivity of the alkynyl ethers compared to the analogous thioethers. Since overlap of the empty p orbital on the vinyl carbon must be much better with the lone-pair electrons in the 2p orbitals of oxygen than with the lone-pair electrons in the more diffuse 3p orbitals of sulfur.

210

PETER J. STANG

2. Electrophilic Additions to A rylacetylenes

Although the reaction of certain acetylenes such as phenylacetylene and ethyl phenylpropiolate with cold concentrated sulfuric acid to give acetophenone (1 5 ) and benzoylacetic acid (1 6) has been known since the 1880's, it was only in the 1960's that this reaction was studied mechanistically. The relative rates of hydration of arylacetylenes in acetic acid: water: sulfuric acid to the corresponding acetophenones were investigated by Bott et al. (17), and they are listed in Table I. TABLE I Hydration of Substituted Phenylacetylenes in Acetic Acid : Water : Sulfuric Acid at 50.2"C(17) Substituent mCF, m-Br m €I p-Br P-I PC1

m-Me0 H mCH, p-2-B~ P-W P-CH 3 0

ki

krel

.0047 ,018 .021 .22 .24 .28 .52

1 .oo 1.92 10.5 15.6 950.0

As the data in Table I indicate, there is a strong dependence of the hydration on the electron demands of the substituents, with a rho of -4.3 in the Yukawa-Tsuno (18) equation, where log k is plotted against p [a + r ( d - a)]. Partial hydration of C6 H5CE CT and recovery of the unreacted starting material did not result in any loss of specific activity, which indicates that the protonation of the triple bond is not significantly reversible and hence is rate determining. A more detailed study of the hydration of phenylacetylene, 9a, and three substituted phenylacetylenes, p-methoxy 10, p-methyl 1 1, and p-chlorophenylacetylene 12, in aqueous sulfuric acid containing 5% ethanol has been carried out by Noyce and co-workers (19,20). The hydration obeys general acid catalysis and gives a linear Ho dependence. The slopes for the logarithm of the observed rate constants versus Ho and the activation parameters for the hydration of these phenylacetylenes are summarized in Table 11.

VINYL AND ALLENYL CATIONS

211

TABLE I1 Acidity Dependence and Activation Parameters for Hydration of Phen ylacet y lenesa Compound 9a

10 11 12

T,"C

24.92 44.11 24.88 44.93 24.88 44.93 24.86 44.63

- _log _ dH0 1.24 f .01 1.189 f .006 1.185 f .015 1.005 f .008 1.26 i .03 1.149 f .001 1.17 f .01 1.195 i .006

AHS(kcal/mole)

ASS(e.u.)

20.9

-18.2

15.7

-21.6

21.6

-10.4

16.7

-33.6

a Data from (20).

Noyce and Schiavelli (21) also measured the rate of hydration of the above phenylacetylenes in deuteriosulfuric acid solution. Values of the observed solvent isotope effects, kH,O/kD,O, are summarized in Table 111. TABLE I11 Solvent Deuterium Isotope Effects for the Hydration of Phenylacetylenes at 250a Compound 9a

10 11 12

-H, range

2.34-3.24 -.73-.60 .85-2.12 1.91-3.21

(kH,sO,/kD

(kH, s o , / k ~ so,)' ,

2.67-3.32 2.67-3.1 8 2.39-2.74 2.97-3.10

2.46 3.82 2.70 2.98

a Data from ref. (21).

Range of values observed over the acidity range. Isotope effect at Ho = -2.0.

The experiments of Bott (1 7) and Noyce (19-2 1) show that a vinyl cation best represents the intermediate in the hydration of phenylacetylenes. In particular, the large solvent isotope effects observed indicate a rate-limiting protonation and formation of a vinyl cation, for these values are not in agreement with solvent isotope effects observed for compounds which react by other possible mechanisms, such as one involving equilibrium formation of the vinyl cation followed by the slow attack by water.

212

PETER J. STANG

*

From a knowledge that the equilibrium C6H5CzCHt H 2 0 C6HSCOCH3 lies 37 kcal/mole in favor of the ketone (22) and of the data of Ziicher and Hammett (23) on the rate of enolization of acetophenone, combined with an estimate of the enol content of acetophenone (.00190) (24), Noyce and Schiavelli (20) have summarized the above data in an elegant energy-reaction coordinate diagram, shown in Figure 1.

Reaction coordinate

Figure 1. Energy-reaction coordinate diagram for the acid-catalyzed hydration of phenylacetylene. The ordinate is not to scale (20).

Rate-determining protonation to give a vinyl cation rather than 1,4 addition of water has been proposed as the most consistent mechanism (25) for the acid-catalyzed hydration of arylpropiolic acids in aqueous sulfuric acid. Hydration of arylpropiolic acid closely resembles the acid-catalyzed isomeriza-

ArC=GCO,H

0 11 Arc=(-C-OH

H'

ArC=CHCO,H HZ

H+

6H 11 Arc=(-C-OH

H O

OH I ArC=CHCO,H

-+

Products

+

Products

+OH, OH I

I

1 ArC=C=C-OH

VINYL AND ALLENYL CATIONS

21 3

tion of cis-cinnamic acids, which has been demonstrated to occur by a rate-determining protonation of the double bond (26):

The rates of hydration of substituted phenylpropiolic acids give a rho of -4.77 when plotted against u’ , comparable to ’the acid-catalyzed isomerization of cis-cinnamic acid, with a rho value of -4.3. The solvent deuterium isotope effects are kH2S04/kD2S0, = 3.7-5.2 for the isomerization of cinnamic acids at 45°C and 2.4 - 5.3 for the hydration of arylpropiolic acids at 25°C in 50% sulfuric acid. The rates of both reactions give a linear correlation when plotted against Ho , with a slope of near unity; and both reactions have comparable high negative entropies of activation. In contrast, the acid-catalyzed hydration of arylbenzoylacetylenes differs markedly from the hydration of a,P-unsaturated ketones. Hydration of unsaturated ketones has been shown to proceed via a 1,Caddition mechanism where protonation occurs on oxygen to give an oxonium salt, followed by attack of water at the 0-carbon to give a hydroxy enol. The rate-limiting step has been shown to be the protonation of the hydroxy enol(27): 0 eOH OH OH 11 H+ II I I RCH=CHC-R # RCH=CHCR 4 RCHCH=C-R OH OH I I RCHCH=C-R + H

slow

0 @OH OH I1 I II RCHCH2CR + RCHCH, CR OH I

In contrast, the hydration of arylbenzoylacetylenes is believed to proceed via a vinyl cation formed by rate-determining protonation on carbon (28): 0 II XC, H,C*-C-C,

H,

+H

-

e slow

0 I1 XC, &C=CHCC, H, @

--+ --+

0 0 II II XC6H4CCH2CC6H5

The evidence presented includes the observed solvent isotope effect of the high negative rho of -4.21, and the high negative entropies of activation (-27 e.u. to -35 e.u.). The negative entropy of activation is in line with values observed for other rate-limiting transfers to unsaturated carbons (29). Vinyl cations also have been invoked as intermediates in the electrophilic addition of HCl to 1-phenylpropyne in acetic acid. Fahey and Lee (30,3 1) have shown that the reaction is first order in 1-phenylpropyne and between first and second order in HC1. The observed products were cis-(-75%) and truns-(-lO%) 1-chloro-1-phenylpropene,along with about 15% propiophenone. Control experiments demonstrated that the propiophenone arose from cis- and trans1-acetoxy-1-phenylpropene. The results were best explained by rate-determining kH2S04/kD2S0,=2.2-3.9,

214

PETER J. STANG

protonation and formation of vinyl-cation ion pairs rather than by a concerted cyclic addition, which would have required the formation of all cis products. Recent studies by Pincock and Yates (32, 33) have demonstrated the intermediacy of vinyl cations in the electrophilic bromination of arylmethylacetylenes in acetic acid. The rates of addition of Br2 to a number of substituted phenylmethylacetylenes in acetic acid follow the general equation

where [AMA] is the concentration of arylmethylacetylene; [Brz ] the bromine concentration; and k2,k3 and kBr- are specific rate constants. The term in kBronly applies in the presence of added bromide ion. A rho value of - 5.2 was observed for a plot of log kz vs. u* in this reaction. This value is comparable to those observed in the acid-catalyzed hydrations of various arylacetylenes (20,25,28) as well as to the rho value of -4.5 observed in the bromination of styrenes in acetic acid (34,35). In accord with previous observations in rate-limiting electrophilic additions, the entropies of activation are highly negative, with values around -30 e.u. The products of addition consist of about 70% trans- and 13% cis-l,2-dibromoolefins, C6H5CBr=CCH3(Br), along with 27% of solvent-incorporated products. The solvent-incorporated products are regiospecific in the Markovnikov sense, consisting of cis- and trans-l-acetoxy1-phenyl-2-bromopropeneand 0 II C, H,CCBr,R.

The dibromoketone is formed from the bromoacetates in a secondary reaction. These results have been accounted for by the authors via an ion-pair scheme shown in Figure 2. In contrast to the above behavior, in the presence of .1 M LiBr phenylacetylene yields the trans dibromide, C6HSCBr=CHBr, in greater than 99% yield upon the addition of Brz in acetic acid (35). This difference in behavior between the two systems has been accounted for by the formation of a different intermediate ion, 13, in the latter case.

13

Cleavage of arylethynyltriethylgermanes by perchloric acid in aqueous methanol has been proposed to proceed via a vinyl cation (36). A rho value of -3.3 was

cHap;)H * Ar&CHGe(Et),

ArC-=CGe(Et), +H+

+

ArMH

215

VINYL AND ALLENYL CATIONS Ph-CEC-R

+

/

Br,,C=C,

Br2

Ph

Br R

Ph,

,c=c, /

AcO

R

\

HOAc ‘R

-

l HOAC Ph--d=C: Br-

Br

HOAc + ,Br Ph-CaC,

I

HOAc

Br

/

R

Figure 2. General ion-pair scheme for the addition of bromine to phenylacetylene in acetic acid (33).

observed for this reaction in the Yukawa-Tsuno relation. Vinyl cations may also be involved as intermediates in the formation of lactones in sulfuric acid from diarylacetylenes with ortho carboxyl groups (37). However, this reaction may also proceed by a concerted process, and it is difficult to establish the exact reaction mechanism. Once again, a large amount of diverse evidence indicates the intermediacy of a vinyl cation in electrophilic additions to arylacetylenes. As in the case of the hydration of alkynyl ethers and thioethers, the vinyl cation formed is especially stable because of resonance interaction and charge delocalization with the adjacent center of the aromatic system.

3. Electrophilic Additions to Alkylacetylenes and Acetylene Peterson and co-workers have carried out a careful investigation of the electrophilic addition of trifluoroacetic acid to a series of aliphatic alkynes (38) and alkenes (39,40). Of particular interest is the behavior of 3-hexyne. At .1 M concentrations of 3-hexyne, nearly equal amounts of the cis- and trans3-hexen-3-yl trifluoroacetates are formed in 98% yield, together with about 2% 0 II OC-CF3 I

CH, CH, C=CHCH, CH,

of hexaethylbenzene. At a concentration of 1.4 M, the hexaethylbenzene yield

PETER J. STANG

216

increases to 24%. The nonstereospecific addition is consistent with formation of a vinyl cation which can collapse with solvent to give the observed cis and trans trifluoroacetates or react further with unreacted alkyne in solution to form the hexaethylbenzene. The latter product presumably arises via dimeric intermediates, although no dimers as such were isolated. Further evidence for rate-determining protonation and vinyl cations comes from the close similarity of substitutent effects and general behavior for additions of trifluoroacetic acid to alkynes (38) and alkenes (40). Extensive investigations have clearly established protonation as the rate-determining step for electrophilic addition of trifluoroacetic acid to alkenes (40). Addition of trifluoroacetic acid to 5-substituted-1-alkynes of the type (X = I, Br, CI, F, CH,O, OAc, etc.)

X

yields rearranged products presumably through 5-membered cyclic intermediates (41). Formation of such cyclic intermediates could involve vinyl cations, or they could arise via a concerted process. The available evidence would indicate a concerted process rather than discrete vinyl cations.

In contrast to the behavior of 3-hexyne in trifluoroacetic acid, addition of HC1 in acetic acid yields essentially trans-3-chloro-3-hexene (48%) and 3-hexanone (52%) as products, with less than 1% of the cis chloride (3 1,42,43). The 3-hexanone has been shown to arise from an intermediate vinyl acetate. The kinetics are complicated, but they seem to be of first order in substrate and second order in HC1. Added tetramethylammonium chloride increases the rate of product formation and changes the product composition to >95% trans3-chloro-3-hexene and <5% 3-hexanone. A termolecular electrophilic addition via an intermediate such as 14 has been proposed (31,42) to account for these data. A-

14

X = H ; Y = OAcor C1 X = (CH,), N;Y = CI

VINYL AND ALLENYL CATIONS

217

Yet another intermediate, a cyclic bromonium ion, 15, is involved in the electrophilic addition of bromine to 3hexyne, 1-hexyne (32,33), and other alkylacetylenes (44). In these reactions, only trans dibromides have been

-c-=c. , /

s'

Br 0

15

observed as products, formed via bimolecular kinetics (32). Similar cyclic intermediates, 16, have been invoked in the addition of sulfenyl halides to alkynes (45) and aIkenes (46).

--c=c*;&J

S I

R 16

The exact behavior and mechanism of electrophilic additions to alkynes is clearly strongly dependent upon the reaction conditions. In a highly polar and strongly acidic but weakly nucleophilic solvent such as trifluoroacetic acid, addition via a vinyl cation intermediate is favored; whereas in less polar, more nucleophilic solvents such as acetic acid, a different mechanism prevails. The addition of hydrogen halides to methylacetylene also has been investigated (47,48). When the additions were carried out neat in a 1 : 1 ratio at -7O"C, besides two acyclic products, CH3CX=CH2 and CH3CX2CH3,substantial amounts of two cyclic products, cis- and truns-l,3-dihalo-l, 3-dimethylcyclobutane were observed along with some minor products (48). Similar results were observed in the addition to allene (vide infra). Although no substantial experimental evidence other than the observed products was offered, the results were accounted for by a vinyl cation hypothesis (48). Protonation yields the intermediate vinyl cation 17, which could collapse to give product 18 or react with excess propyne to give the observed cyclic products.

CH,CH=CH

+ HX

[CH,C=CH, J

l7

X I

b

CH,--C-CH,

I

-

CH,CX=CH,

b

I

H, C-C-CH, I X

1. ~e

CH,-C-CH,

t -

*. HX

I

I

HCsC-CH,

7

18

kCrCH CH,-C=CH,

IC.

H-C=C-CH, b

In contrast to the work of Peterson (38) with 3-hexyne in trifluoroacetic acid (vide supra), n o trimeric adducts were observed in the hydrogen halide additions to propyne (48).

PETER J. STANC

218

Vinyl cations also have been invoked as intermediates in the reaction of HCl with t-butylacetylene (49). With neat mixtures in the liquid phase at ambient temperatures, the following four products were observed: CI t-Bu-C=CH,,

(CH,),CCI,CH,,

(CH,),CClCCI(CH,),,

CH, C1 I I CICH,CH C(CH,),

19

20

21

22

I

Products 19 and 20 result from the collapse of vinyl cation 23 with CI- to give 19, and the subsequent reaction of this product with HCl gives 20. Compounds 2 1 and 22 could arise from either a 1,2-methyl shift to vinyl cation 23 or CH, CH3 I I m CH,-CXkCH+HCl+CH,-C-C=CH, I I CH, CH, 23

via neopentyl-type rearrangements. Thus, 21 could be formed by a methyl migration during the addition of HCl to 19 and 22 by a series of two anti-Markovnikov additions to t-butylacetylene and a concurrent methyl

c1

CH, I m f-Bu-C=CH, +CH,-C- C-CH, I I CH, C1

H+

I

C1 m

I

(CH,),C-C(CH,),

Cl* __+

21

19

migration during the second addition step (49). However, reaction of an H+

HCI

(CH,),C-C*H

(CH,),CCH=CHCI

+

24

-f

CH, CH, I I (CH,),CCHCH,Cl+ gC- CH-CH,CI m

I

CH3 J.

c1-

22

authentic sample of 19 with HCl produced no 21, but only 20, and the formation of 22 from authentic 24 and HCl is too slow under the reaction conditions employed to account for its formation via this route. Hence, 21 and 22 arise via a 1,2-methyl shift to vinyl cation 23 and the subsequent reaction of the resultant rearranged allylic ion. (For a detailed discussion of rearrangements in vinyl cations, see section IV.F.l.) Vinyl cations also have been invoked as intermediates in the addition of carbonium ions generated in strong acid to acetylene (50-53). Sasaki et ai. (SO) observed 1-adamantyl methyl ketone, 25, as the sole product in the reaction of acetylene with 1-bromoadamantane in concentrated Hz SO4 at 5". Bott (5 1 ), on the other hand, reported a mixture consisting of 75% 1-adamantylacetaldehyde,

VINYL AND ALLENYL CATIONS

219

26, and 25% methylhomoadamantanone, 27, in the reaction of l-hydroxyadamantane with acetylene in 90-95% H2SO4 at 4-7'C. Presumably the first

26

25

27

step in each of these reactions is the formation of the stable adamantyl carbonium ion, which then adds to acetylene to give a vinyl cation intermediate 28.

X = OH, Br

28

The subsequent fate of this intermediate primary vinyl cation 28 seems to be in doubt and dependent upon the exact reaction conditjons. In concentrated (98%) Hz SO4, ion 28 seems to undergo a rapid hydride migration to form the more stable vinyl cation 29, which in turn is trapped by water to give ketone 25

G

c

H

28

E

H

-

%

&-z-CH2

25

29

as the major or sole product (50); whereas in 90-95% sulfuric acid, ion 28 is mostly trapped to give 26 as the major product, with only 25% rearranged product 27 ( 5 1). Product 27 was proposed to arise as follows (5 1):

21

However, more recent evidence (53) indicates that sulfates may be involved as intermediates and the rearranged product 27 arises via a synchronous process rather than through ion 29. Direct protonation of adamantylacetylene in 90%

2 20

PETER J. STANG

sulfuric acid in turn gave 32% of ketone 25 and 68% of ketone 27, presumably through vinyl cation 29 (52). (For a more detailed discussion of this system, see Section IV.F.l.)

B. Electrophilic Additions to Allenes 1. Addition to Allene

Electrophilic addition to allenes can occur via either of two ways: (a) addition to the terminal carbon and formation of a vinyl cation or (b)

addition to the central carbon and formation of an allylic-type carbonium ion.

\C=C=C /

/ \

E I I + E + + C=C-C@-+ I

Although at first glance addition to the central carbon and formation of what seems like an allylic carbonium ion would clearly be preferred over terminal addition and a vinyl cation, a closer examination shows this not to be the case. Since the two double bonds in allenes are perpendicular to each other, addition of an electrophile to the central carbon results in an empty p orbital, which is perpendicular to the remaining n system and hence not resonance stabilized (and probably inductively destabilized) until a 90" rotation occurs around the newly formed single bond. Hence, allylic stabilization may not be significant in the transition state. In fact, electrophilic additions to allene itself occur without exception at the terminal carbon (54). Hydration of allene in sulfuric acid yields acetone, presumably via a vinyl cation intermediate (55, 56). Addition of HC1 and HBr to allene results in

CH,=C=CH,

H+

CH,-?=CH,

0 II H2q CH,C-CH,

2-halopropenes, 2,2-dihalopropanes, and cis- and trans-l,3-dihalo-1,3-dimethylcyclobutane via a vinyl cation (57). These products and their relative amounts were identical to those observed in the addition of HCl and HBr to propynes (48) and presumably proceed via a similar mechanism (vide supra). In contrast to acid-catalyzed hydration and additions of HCl and HBr,

221

VINYL A N D ALLENYL CATIONS

addition of halogens Cl, or Br, to allene proceeds through a cyclic intermediate (58, 59), such as 30, rather than through a vinyl cation.

2. Addition to Substituted Allenes Even substituted allenes, RCH=C=CH2, are protonated at the 1 position, giving methyl ketones by hydration (60-63) and mostly 2-halo-2-alkenes, RCH=CXCH3, by the addition of hydrogen halides (62, 64, 65). Jacobs and Johnson (65), in a careful study, have shown that addition of HCI to 1,2-butadiene, CH3CH=C=CH2, at -78°C occurs with exclusive formation of cis- (8.1%) and frans- (52.1%) 2-chloro-2-butene. No allylic products resulting from central protonation were observed. Isomerization to 2-butyne was observed, but control experiments demonstrated that addition to the allene occurred faster than addition to 2-butyne (65). The turning point towards central protonation seems to occur with 1,3-dialkylallenes, RCH=C=CHR', with the ratio of central to terminal protonation strongly dependent upon the exact reaction conditions. Hydration of 1,3-dialkylallenes in sulfuric acid yields the corresponding ketones, RCH2COCHzR', (66), whereas addition of HBr at -40°C yields products of mixed orientation (67,68). Addition of HCl to 1,2-~yclononadienegives mostly, RCH=C=CHCH,

HBr RCH=CBrCH, CH, + RCH=CHCHBrCH, -40" _

_

f

if not exclusively, central protonation and the allylic chloride (69). Central protonation and formation of the stable 1,3-dimethyIallyl cation, 3 1, is observed CH3CH=C-CHCH,

FSO.H-SbFs

- 70"

H

H

b

H3C

H 31

upon addition of 1,3-dimethylallene to FS03H-SbFS at -70°C (70). The formation of any vinyl products in electrophilic additions to RCH=C=CH2 and RCH=C=CHR' is surprising, since central protonation should yield a secondary carbonium ion compared to terminal protonation and formation of a vinyl cation. Perhaps a secondary carbonium ion destabilized by

222

PETER J. STANC

an adjacent perpendicular IT center is less stable than a vinyl cation. The contrast in behavior of allenes in sulfuric acid (66) and FS03H-SbF5 (70) is also puzzling. However, the direction of protonation can be reversed by substituents that increase the stability of the positive charge at the terminal position. Acid-catalyzed hydrolysis of allenyl ethers (7 1), for instance, proceeds via cental protonation, presumably because of the special stability of the intermediate carbonium ion 32. OH I RCH=C=CHOEt --* RCHZCH-CHOEt + RCHZCH-CHOEt He

e

17

32

RCH=CHC-H

In contrast to the above case, addition of HCl to 1,l-dimethylallene at -78" C gives at least two thirds and possibly exclusively l-chloro-3-methyl-2butene, 33, although these results are complicated by rearrangement of the allene to isoprene and the addition of HCl to the isoprene (65).No satisfactory explanation was offered (65) and none is readily available within the carbonium framework to account for the unusual orientation in this addition. Certainly the tertiary carbonium ion, 34, should be more stable than the primary carbonium ion, 35, since neither is stabilized by the adjacent perpendicular IT center. This result is all the more surprising since tetramethylallene, 36, behaves as expected

c1

e

+ CH3-C-CH=CH,+

I CH,

I (CH3),C-CH=CH,

34

in electrophilic additions and reacts via central protonation and formation of tertiary ion 37 (68 72). ,CH,

CH,

\C=C=C, CHI 36

-+

CH,

YH3 '\C=CH-C@-+ Products I CHf CH 3

H + CH

31

In contrast to the behavior of tetramethylallene, allene 38 undergoes central protonation in electrophilic additions. In an acetic acid: sulfuric acid

223

VINYL AND ALLENYL CATIONS

mixture, for instance, 38 yields three products: 2,3,3,6-tetramethylhept4-yn-1-ene, 39; 2,3,3,6-tetramethylhept4-yn-2-01, 40; and the corresponding acetate, 41, in a ratio of 27 : 36 : 37 (73).

40 R = O H 41 R = O A c

39

38

A more careful investigation of this system was undertaken by Poutsma and Ibarbia (74), who have demonstrated that acid-catalyzed rearrangement of allene 38 as well as acidcatalyzed addition of hydroxylic solvents, chlorination, bromination, and cycloaddition with chlorosulfonyl isocyanate give products resulting from terminal electrophilic attack, whereas epoxidation and mercuration result in attack on the central carbon. The difference in behavior between allene, 38, and tetramethylallene, 36, may result from the stabilization by the neighboring cyclopropane ring of the vinyl cation, 42, resulting from terminal protonation, which opens up to the tertiary ion 43, the precursor of the

42

43

44

observed products. However, as the authors point out (74), in the absence of further information it is difficult to ascertain whether 4 2 or 43 are distinct energy minima or whether perhaps a structure such as 44 best represents the cationic intermediate. Furthermore, observation of some triene, 45, indicates that terminal protmation, although favored, is not exclusive; some central protonation must also occur (74). CH, I

CH

)=C=CH-C, CH3

J-CH3 C=CH, I

CH3 45

A summary of electrophilic additions to triple bonds and allenes involving a vinyl cation is given in Table IV.

N

-

1.2~ lo-, -

25.0 25.0

buffered H,O buffered H,O

II C,H5Cd-C-C,H,X

0

XC,H,MCOOH 0 II XC,H4M-C-C6H5

25.0

27-77%aq. H,SO, 25.0

25.0

50% aq. H,SO,

60-78%aq. H,SO,

2.8 x lo-"

25.0

-

-

2.8 x 10.' 2.8 x lo-''

2 : 1 HOAc : aq.H,SO, 44%aq. H,SO, 6.2%aq. H,SO,

.02

-4.2d

-4.gd

-3.8d

-

-4.3b

50.2 25.0

RGC-S-Et (R = Me, Et, n-Pr, i-Pr) XC, H , M H C, H , M - C H , XC,H,MH -

25.0

buffered H,O

HGC-S-R (R = Et, i-Pr, t-Bu)

0

C,H,CO,CH,COC,H,X

XC,H,COCH,COC,H,

II 11 XC,H,CCH,COOH, CO, +XC,H,CCH,

0

28

28

19,25

17 19 20

9

0 II RCH,C-S-Et

-3.8a

25.0

XC,H,COCH, C, H ,COCH ,CH, XC,H,COCH,

9

0 I1 CH,C-S-R

-.7a

5 537

Ref.

13 13

CH,CO,CH, CH,CO,R

Major products

EtC0,Et RCH,CO,Et

-2.6=

buffered H,O -

-6.2a

-

3.4 lo-, -

25.0 25.0

rho

buffered H,O buffered H,O

k, sec-'

Hm-0-Me HGC-0-R (R = Et, n-Pr, i-Pr, t-Bu) CH,M-O-Et R-Cd-0-Et (R = Et, i-Pr, n-Bu)

T, "C

Reaction Conditions

Substrate

Summary of Electrophilic Additions to Acetylenes and Allenes Involving Vinyl Cations

TABLE IV

m

m m

0

m

m

m

m m

M

0

I

I

I

1

I

I

I

2

8

X

I

9

9

9

9

v)

N v)

N

hl

N

E 4

v,

n

2

2

3:

Y

5 2 25

10

Lo

W

w

00

rn

d

m

d

d

U

I

z W

h

I

I

/

I

I

I

I

1

I

I

8 "

9

9

8 W

I

I

-

?

I

o m l - m I

Y

m

E

2 26

3

.. -

p'

10 0 v,

3

00'

v)

d

x

"

r"

"n"

v,

+

u u r"

+

8I

3 V I

0--u

0-U

x p (c1 '

I

I

I

9

v,

"

0-

?

I

I

I

I

0

0

x

rI

6 4 3:

I

m

3:

4

..

d

3

4

+ 3:

QI

I-

221

I

00

Me

Me

ap* using Taft's u*. Yukawa-Tsuno relation. Rate of parent compound X = H. p using Brown's 0'.

,c=c=c

reflux 80" 0-25" reflux

H,O-THF-H,SO, HOAc-H,SO, CF3COOH : C,H, CH,OH-H,SO,

Me,

-40

HBr

CH,CH=C=CH,

--78

HCI

CH,CH=C=CH,

T, "C

Reaction Conditions

Substrate

-

-

-

-

-

-

rho

k, sec-'

Table IV-(continued)

CI

/

CH3\

H '

CH,

c=c'

,CH, H

/c=c\

CH,

C1,

Me MeMe I I I HCWC-C-OS I I I Me MeMe

+

I

Me

HC-C=C

Me

Me

\

C=CH,

J-Me

/

Me Me

Me Me I I &CH, Me\ H - C - M -C -C, Me + Me,C=CH-C\ I I Me Me

40% 8.1% 52.1% CH,CH,CBr=CHR + CH,CHBrCH=CHR

CH,MH,

Major products

14

67,68

65

Ref.

229

VINYL AND ALLENYL CATIONS

111. VINYL CATIONS BY MULTIPLE-BOND PARTICIPATION

IN

SOLVOLYSIS Multiple-bond participation in solvolysis may be looked upon as a competition in a nucleophilic displacement between solvent and the n electrons of the multiple bond or as an electrophilic addition of a carbonium ion, or carbonium ion like species, to the multiple bond. A. Participation by Triple Bonds Vinyl cations probably are involved as intermediates in the solvolysis of homopropargyl derivatives, 46, extensively investigated by Hanack and coworkers (75-79). The products of reaction are cuclobutanones, 47, cycloR - C e - C H , -CH,-X 46

OSO,C,,H,,

X = OSO,C,H,CH,

OSO,C,H, -m-NO,

propylalkyl ketones, 48, and unrearranged homopropargyl esters, 49 (75-77). Product composition is strongly dependent upon the polarity and nucleophilicity of the solvent. In a solvent of low polarity and high nucleophilicity,

RC=CCH,CH,X

-a R

46

+

0 I

C-R+

0 1 I RCECCH2CH20C-R’

O

41

49

48

such as acetic acid, the major product, in greater than 98% yield, is the unrearranged homopropargyl acetate, whereas in formic acid the product distribution is 16% of 47, 1% of 48, and 83% of 49. In trifluoroacetic acid, a solvent of high ionizing power and low nucleophilicity, 85% of the product is the rearranged ketone 47, 9% the cyclopropyl ketone 48, with only traces of unrearranged products (77). Increased cyclization is also observed as the leaving group X changes from tosylate to m-nitrobenzenesulfonate and to 3,5-dinitrobenzenesulfonate (77). It has been suggested that this behavior indicates the direct participation of the triple bond in the solvolysis and formation of vinyl cations 50 and 51 (79). Further evidence for this mechanism comes from the 0

51

PETER J. STANG

230

lack of observation of products resulting from the electrophilic addition of solvent to the triple bond of 46 or the precursor propargyl alcohols under solvolytic conditions. Strong support for direct participation of the triple bond and involvement of 51 is the observation in the nmr of the cyclic trifluoroacetate 53 in the trifluoroacetolysis of 52, which upon addition of a small amount of water instantly gives the product ketone 47, R=Et (79). CH3CHzC~C-CHz-CHz-OSOzC6 H4NOz 52

I

CF3COOH

0

CH,CHz L L O - J - C F 3

53

-

47

Solvolysis of the deuterium-labeled precursor, 54, indicates that the intermediate ion 5 1 arises from a symmetrical precursor, as the product ketone 55 has an equal distribution of deuterium in the 3 and 4 positions. CH,CZCCHzCDzOSOzC,H4NOz CFsCOOH

54

CH,

0 55

Direct formation of 51 would have placed the deuterium exclusively at the 3 position (79). The observed scrambling has been explained by the prior formation of ion 50, which rapidly rearranges to 51 and yields the observed cyclobutanone products (79). The involvement of ion 51 as an intermediate is surprising, for it would be expected to be highly strained. A more likely intermediate may be a bridged species such as 56, which upon collapse with

56

solvent would give the observed products and could also account for the deuterium scrambling. Formation of rearranged products in the solvolysis of homopropargyl systems need not involve triple-bond participation and vinyl cations in all instances. Ward and Sherman investigated the formolysis of 4-phenyl-l butyn-1-yl brosylate, 57 (80). At 80°C in the presence of one equivalent of pyridine, they observed formation of phenyl cyclopropyl ketone, 58, and

VINYL A N D ALLENYL CATIONS

231

4-phenyl-3-butyn-l-ylformate, 59, both of which reacted further with solvent to yield some y-formoxybutyrophenone 60. The authors reasoned that if solvent

59

J

57 0 -

II L~Hs C(CH2)S

OCHO

60

could add to the triple bond of 59, then it might also add to 57, and the cyclic product 58 might arise from double-bond participation of the resulting enol formate 61 rather than triple-bond participation and a vinyl cation. Indeed, when 57 was heated at 50" C in anhydrous formic acid containing one equivalent of benzenesulfonic acid, after 15 min the nmr spectrum of the reaction mixture clearly showed the presence of the isomeric enol formates 61 (80). OCHO I

C,H,C=CCH,CH,OBs 6 1, cis and trans

When two equivalents of pyridine were added to the nmr sample and the probe heated t o 8O"C, the enol formate 61 decreased and phenyl cyclopropyl ketone 58 appeared at a rate approximately ten times faster than in the previous buffered system. The observation of intermediate 61 and the kinetic results, together with the observed induction periods, are consistent with the idea that some and perhaps all of the rearranged product ketone in the solvolysis of this system arises via double-bond participation in 6 1 rather than triple-bond participation and a vinyl cation (80). However, the observations of Ward and Sherman need not rule out triple-bond participation and vinyl cations in the systems studied by Hanack and co-workers (75-79). Presumably, the enol formate 61 itself arises via a transition state involving a rate-determining protonation and vinyl cation 62 (see previous section). A vinyl cation such as 6 2 with an adjacent phenyl group is considerably more stable and hence more accessible than a vinyl cation such as 63, stabilized only by a neighboring alkyl group. Hence, formation of enol formate 61 and its tB

C,H,C=CH,CH,CH, OBs 62

tB

RC=CCH,CH,CH,X 63

R = alkyl

PETER J. STANG

232

subsequent reaction is the low-energy and preferred process in the solvolysis of 57, whereas triple-bond participation may be the lower-energy and preferred process in the solvolysis of systems such as 46. Triple-bond participation was'also observed in the formolysis of 64 (81). Tosylate 64 in formic acid at 60" in the presence of sodium formate gave a nearly quantitative yield of 5-methyl-4-hexen-3-one,65. CH, II I CH,CH,C-CH=C-CH, 0

CH3 I CH,M-C-CH,OTS

65

64

When the reaction was followed in an nmr probe, the appearance and disappearance of two intermediates 66 and 67 was observed along with the buildup of product 65. The rate of reaction of 64 at 75" in formic acid, k =3 x sec-', is six times faster than the rate of the corresponding saturated system, 2,2-dimethyl-l-pentyl tosylate, k = 5 x lo-' sec-', under identical conditions. If the inductive rate retarding effect of the triple bond is taken into account, then the calculated rate enhancement resulting from triple-bond participation in the solvolysis of 64 is about 3000 (81). The OCHO

OCHO I CH ,C=CHC=CHCH

I

CH, - C - C H 2 C s - C H 3 I CH3

I

CH 3

66

61

intermediacy of vinyl cation 68 was suggested to explain these observations, as shown in Scheme 111.

64

- -

CH3

I

CH3-C=C

-t

CH3CEC-CH2C@ I

-

66

CH3

68

66

61

65

Scheme 111. Proposed Mechanism of Formolysis of 64 (81).

Participation of more remote triple bonds has also been investigated. Peterson and Kamat (82) have carried out a careful study of the solvolysis in a variety of solvents of 6-heptyn-2-yl tosylate, 69, and 6-octyn-2-yl tosylate, 70. The observed products of solvolysis are given in Schemes IV and V.

VINYL AND ALLENYL CATIONS

233

-42Ts 70

7 O T s 69

71

72

13

74

Scheme IV. Products of Solvolysis of 69.

O ' V "'g 76

IS

+" O W +

+

+

RoQ

77

78

Elimination

79

OJ?

80

81

82

Scheme V. Products of Solvolysis of 70.

The primary rearranged products 71, 75,76, 77, 78 were converted to the corresponding ketones, 73, 80, 81, and the primary acyclic products 72 and 79 into their respective acyclic alcohols, 74 and 82. As the solvent polarity increased and the nucleophilicity decreased from acetic to formic to trifluoroacetic acid, the rearranged products increased significantly from 27% to 91% for 69 and from 60% to 100%in the case of 70. The formation of the rearranged

234

PETER J. STANG

vinyl tosylates 76 and 78, resulting from internal return, in the solvolysis of 70 is of particular interest. Also in the solvolysis of 70, the five-membered ring products dominated over the six-membered cyclic products in the rearrangement products. Rate studies, taking into account the retarding inductive effects of the triple bond, indicate that ,the rate enhancement resulting from triple-bond participation in the trifluoroacetolysis is 6.5 for 69 and 8 4 for 70. The authors (82) prefer to explain these results with a bridged ion 83 rather than distinct vinyl cations such as 84 and 85.

83 R = H , C H ,

85 R = H , CH,

84 R = H , C H ,

Their reasoning is based on the difference in energy between a bent secondary vinyl cation such as 84 and a linear secondary vinyl cation such as 85. The authors, based on a third of the difference in ground-state ionization potentials for a carbon 2s and 2p orbital, estimate this difference to be 77 kcal/mole in favor of the linear ion 85;yet despite this large difference, there are significant amounts of 6-membered cyclic products, which, in the authors' opinion, rule out distinct bent and linear vinyl cations such as 84 and 85 (82). A vinyl cation is probably an intermediate in the acetolysis of 6-phenyl5-hexynyl brosylate, 86. At 80°,despite the inductive effect of the triple bond, the rate of acetolysis of 86 is comparable to that of the saturated analog and yields, besides the acyclic acetate 87,36% of the rearranged acetate 88 (83). The exclusive formation of the five-membered ring rearranged product with none of

C,H,CWYCH,),OBs

AcOH

86

(?Ac C,HSC=C(CH,),OAc 87

+ 88

the six-membered ring probably results from the stabilizing effect of the phenyl group in the intermediate vinyl cation 89 relative to 90:

"-0

c6HS%

C6H5

89

90

hence its ability to orient the cyclization reaction. Prior addition of solvent to 86 probably is ruled out by the recovery of the 64% unrearranged acetate 87 with its triple bond intact, as electrophilic addition to 86 should be comparable to that of 87.

235

VINYL AND ALLENYL CATIONS

Recently Johnson and co-workers (84) have taken advantage of triplebond participation in biogeneticlike olefinic cyclizations. Treatment of trienynol 91 with 2%by weight trifluoroacetic acid at -70°C in methylene chloride gave largely the tricyclic triene 92 as product. Similarly, trienynol 93 underwent cyclization under the same conditions to give tricyclic product 94.

CF3COOH

- 70"

CHiCir,

91

92

93

94

-

Under slightly different conditions, treatment of dienynol 95 in pentane with excess formic acid at 23" gave the enol formate 96 as product. Interestingly,

@

&

pHCOOH enme, 23"

Ho

OH 95

96

in no case was a six-membered-ring product observed, which indicates that the linear vinyl cation 97 was preferred over the bent cyclic vinyl cation 98. R I@

@@

H

PETER J. STANG

236

In an elegant extension of this work (85), advantage was taken of such remote triple-bond participation in olefinic cyclizations in the preparation of dlprogesterone from an acyclic precursor. Treatment of trienynol 99 with CF3COOH in 1,2-dichloroethane containing ethylene carbonate (to trap the intermediate vinyl cation 100) followed by workup with aqueous methanol containing excess K z C 0 3 gave the tetracyclic ketone 101 as product. Ozonolysis of ketone 101 gave the triketone 102, which upon treatment with 5% KOH underwent an intramolecular aldol condensation to give, after purification, progesterone, 103 (85). I

--+

99

-

&O ’0

’ 0

& /

0

102

I03

Transannular participation of a triple bond has been examined by Hanack and Heumann (86). Acetolysis or solvolysis in aqueous acetone of cyclodecyn5-yl-I-tosylate 104a gave, besides some unidentified unsaturated hydrocarbons, a mixture of the rearranged ketones 105 and 106. None of the unrearranged

&+JJ(-J+(

X

104a X=OTs 104b X = OAc 1 0 4 ~X = O H

105 cis and trans

106

acetate 104b or alcohol 104c was observed, which indicates that triple-bond participation is favored over direct displacement by solvent. In the absence of

231

VINYL AND ALLENYL CATIONS

kinetic and other data, it is not possible to decide whether the solvolysis proceeds via the bridged ion 107 or through discrete vinyl cations 108 and 109.

108

107

109

B. Participation by Allenyl Bonds Participation by cumulative double bonds and vinyl cation intermediates has been suggested in the solvolyses of a number of homoallenyl systems. Hanack and Haffner (87) reported the solvolyses of 3,4-pentadienyl 0-naphthalene sulfonate, 110 ( R = H ) under a variety of conditions. The products RCH=C=CHCH,CH,ONps 110 R = H, CH,

-

0

tl

RCH2Cg

111 R=H,CHS

+ RCH=C=CHCH,

CH, OH

112 R = H, CH,

of solvolysis after aqueous workup consisted, besides small amounts of unidentified compounds and olefins, mostly of methyl cyclopropyl ketone, 1 11, and 3,4-pentadienol, 112, or the corresponding ester (87). The percentage of rearranged product 11 1 increased with increasing solvent polarity. The rate of acetolysis of 110 (R = H) at 60" was found to be 3.5 times faster than that of n-pentyl fi-naphthalenesulfonate. Similar results were observed in the solvolysis of 3,4-hexadienyl 0-naphthalenesulfonate, 110 (R = CH3), which in acetic acid reacted 9.5 times faster than the n-hexyl sulfonate (88). These results are consistent with formation of a vinyl cation intermediate 113, stabilized by the adjacent cyclopropane ring, in competition with direct solvolytic displacement.

~Z=CHR 113

yH3 CH,=C=CHCH,CHOT~

114

CH, CH, I I CH,=C=CCH,CHOT~ 115

Bertrand and Santelli (89) have investigated the hydrolysis, under apparently heterogeneous conditions, of 4,5-hexadien-2-yl tosylate, 1 14, and 4-methyl-4,5-hexadien-2-~1 tosylate, 115. After 9 0 rnin at 80°,114 upon steam distillation yields a mixture consisting of 3% hydrocarbon; 67% of cis- and trans-2-methylcyclopropyl methyl ketone, 1 16; and 30% of 4,5-hexadien-2-01, 117. When optically active 114 was treated under similar conditions, the resultiiig trans-2-methylcyclopropyl methyl ketone had an inverted configuration at the reaction center, whereas the dienol 117 was found to be racemic (90). This

PETER J. STANG

238

116 cis and trans

117

evidence strongly suggests double-bond participation in the formation of the rearranged product (90). On the other hand, under similar conditions, 115 gives a mixture consisting of 17% cis- and 50% fruns-l,3-dimethyl-2methylenecyclobutanol, 1 18; 17% 1,4-dimethyl-2-methylenecyclobutanol, 119; and 16%4-methyl-4,5-hexadien-2-01, 120 (89). The formation of four-membered

I I9

118 cis and trans

120

rather than three-membered-ring products from 115 may be favored by the allenyl methyl group and may arise directly from the cyclobutyl cations 122 and 123 or via a vinyl cation such as 121, which rapidly rearranges to 122 and 123. H J ~ C H ,

CH3

/

CH, 1 22

..4’

CHz=E@

121

CH 2

123

Furthermore, since no product stabilities were reported (89, 90) under these reaction conditions, it is difficult to determine whether the cyclic products are a result of kinetic or thermodynamic control. Jacobs and Macomber (91) have carried out a careful investigation of the solvolysis of a number of substituted homoallenic substrates 124. By means R 5 ,

,c=c=c

R’S

%x

R2

RZR’,

124 X =OTs or OBs

VINYL AND ALLENYL CATIONS

239

of saturated model compounds, the authors were able to estimate the ratio of the assisted rate kA for double-bond participation relative to the unassisted rate k,. Except for the compound 124, where R1 = R ; = R 5= C H 3 (and R2 = R3 = Rk = H), each compound showed a kA of significant magnitude in acetic acid at 65°C. Of these, the unsubstituted 3,4-pentadien-l-yltosylate 124 (all R s = H) exhibited the smallest value, with kA/k, = .9, while the 2,2,5-trimethylsubstituted compound 124 (R2= R5 = CH3 and R, = RI = R3 = R; = H) had the largest value, with kA/k, = 5150 (91). The accelerative effects of methyl substitution on the acetolysis kA's for 3,4-pentadien-l-yl tosylates (65") relative to the unsubstituted compound can be summarized as 3.20 L

3.77

C= C=C,

d

13 d

C

,C-OTs

/*

271 (gem-dimethyl)

A good correlation was found between the fraction of cyclized or rearranged products and the extent of participation kA/k,. Similar results were observed by Santelli and Bertrand (92) on essentially the same systems. Jacobs and Macomber (91) as well as Santelli and Bertrand (92) suggest a bicyclobutonium ion 125 as the first formed intermediate (with the predominance of I

/I 125

positive charge at C3 and C,) in cases where homoallenyl participation is significant. However, their results d o not exclude formulation of the intermediate as a homoallyl cation, a cyclopropylcarbinyl-typevinyl cation, or even some other ion (91). In fact, it seems that the exact intermediate depends strongly upon the substitution pattern (vide infra) and may well involve rapid interconversion among various bicyclobutonium ions and cyclopropylcarbinyltype vinyl cations and perhaps other species. Bly and co-workers (93-95) have studied the solvolysis of neopentyl-type homoallenic brosylates, 126. The rates of acetolysis and other pertinent

126

kinetic data for these substrates are summarized in Table V. As the data in Table V indicate, 3-methyl substitution causes a rate enhancement of about 2.6 and 5-methyl substitution about 3.5. The results of

PETER J. STANG

240

TABLE V Summary of Kinetic Dataa o n the Acetolysis of Neopentyl-Type Homoallenic Brosylates 126 at 75°C Compound

R’,

R,

R,

lo4k, sec-’

k,,l

Estimated rate enhancement

126a 126b 126c 126d 126e 126f

H H H H CH, CH,

H H CH, CH, CH, CH,

H CH, H CH, H CH,

8.15 21.5 29.0 68.9 107.0 221.0

1.oo 2.64 3.56 8.46 13.1 27.1

8,300-58,000 6,20044,000 24,000-140,000 15,000-70,000 42,000-170,000 -

a

Data from ref. (94)

further substitution are multiplicative, and the calculated values are in excellent agreement with the experimental values. The effect of 3-methyl substitution (a factor of 2.6) in the homoallenic neopentyl-type system is similar to that of 3-methyl substitution in the homoallyl system (factor of 3.2) (96) as well as that of saturated neopentyl-type brosylates (factor of 1.9-4.9) (97). The authors suggest (94) that the similarity of these effects indicates a steric origin and that little or no charge is delocalized onto the 3 position in any of these systems. The rate enhancements resulting from homoallenic n-electron participation were estimated by means of Taft’s (1 1) inductive substituent parameters and saturated model compounds (94). It is significant that the rate enhancements that result from homoallenic participation are larger by a factor of about ten than in the case of homoallylic participation in related compounds. The products of acetolysis are dependent upon the substituents and consist largely of olefins, rearranged acyclic acetates, and various cyclobutyl acetates. It is noteworthy that no unrearranged primary acetates were observed, which indicates that the reaction proceeds entirely in an sN1 manner. Furthermore, despite the tendency of saturated neopentyl-type systems to give products resulting from methyl migration (98), no such migration and products were observed in the solvolysis of homoallenic neopentyl systems: CH, I R-C-CH,-X

0s HOS

I

R-C-CH2CH3

I

I

CH,

CH,

7H3 RCH=C=CR-C-CH,-X

____ HoS

x

-*

0s

I RCH=C=CR-C-CH,CH, I

CH,

VINYL AND ALLENYL CATIONS

241

It is also evident from the data of Bly et al. (95), Jacobs and Macomber (91), and Carry and Vessiere (99) that neopentyl-type homoallenic systems do

not yield cyclopropyl derivatives upon solvolysis, in contrast t o the unsubstituted parent system. If they have no substituents at C1 or C3,neopentyl homoallenic substrates yield rearranged acyclic olefins and rearranged solventincorporated products exclusively. If they carry an alkyl substituent at C1, they give both rearranged and unrearranged acyclic products. If a substituent is present on C3 besides the acyclic derivatives, cyclobutyl products also are formed. In an elegant summary, Bly and Koock (95) explain the diverse products and results observed in the solvolysis of all homoallenic systems as shown in Scheme VI. Upon reaction, homoallenic derivatives which solvolyze with n-electron participation form an initial cyclopropylcarbinyl-type ion, 127.

Rl

I

HC Q\

acyclic

R’,RSC=C=C

products

/CR2R‘Z \

+

R,

/R3

Rf5RSC=C==C \ /CHR, R2-C Q\

R‘2 128

129

127

cyclobutyl products

*--

R’5R5C

4

CHR,

R‘Z 130

Ic +

R’,R5CC)R =(R 2Sz R3

131

Scheme VI.Mechanism of Solvolysis of Homoallenic Substrates.

242

PETER J. STANG

When the cyclopropyl ring in I27 has no alkyl substituents, the initial cation is the most stable intermediate and reacts to give predominantly cyclopropyl products (path B). When there is a substituent R 1 at C 1 , path B still dominates, with some ring opening to the secondary acyclic ion 128: some ring enlargement to a cyclobutyl cation (path C) may also occur. In the neopentyl substrates where R2 and R; are methyl and R3 = H, the intermediate gem-dimethylsubstituted cyclopropyl ring of 127 is unstable with respect to the ring-opened tertiary or secondary cations 129 and 128, and rearranged acyclic derivatives are the exclusive products (path A). Finally, in cases where RJ is methyl, ring enlargement (path C) to the tertiary cyclobutyl cations 130 and 131 becomes important. However, it is not impossible that several bicyclobutonium-ion intermediates of the type proposed by Jacobs and Macomber (91), 125, and Santelli and Bertrand (92) may be in rapid equilibrium with ion 127 during the course of the reaction. A recent investigation by Macomber (100) of the system where R2 = CH3, 126 (R; and all other R’ = H), sheds additional light on the mechanism of homoallenic participation in solvolysis. In this case, the value of the integrated rate constant increased significantly throughout acetolysis, implying rearrangement to a system with comparable reactivity. The results were interpreted by means of an ion-pair mechanism shown in Scheme VII.

,OTs H,C=C

CH,

Scheme VII.

Unlike triple-bond participation, no remote cumulative double-bond (allenic) participation in solvolysis has so far been observed or reported. A summary of triple-bond and allenic participation in solvolysis involving possible vinyl cations is given in Table VI.

TV. HETEROLYTIC CLEAVAGE OF VINYL SUBSTRATES All of the above mentioned examples of vinyl cation intermediates have involved electrophilic additions to triple bonds or allenes or participation in solvolyses of such multiple bonds. In a sense, these reactions derive from analogies in normal

VINYL AND ALLENYL CATIONS

24 3

carbonium-ion chemistry in electrophilic additions to olefins and double-bond participation in solvolyses. This analogy can, of course, be extended to heterolytic bond cleavage in solvolytic processes. Most carbonium ions have been generated by heterolytic bond cleavage in solvolyses: R-X

+ R@+Xe

a process in principle applicable to the generation of vinyl cations. However, it has only been in the past few years that such processes have received careful

\ A ,c=c,

\,c=c@ + xe

+

attention and undergone a systematic investigation (101). Historically, there are two main reasons for this earlier lack of investigation of solvolytic reactions of vinyl substrates: first, the suspected high energy of all vinyl cations relative to ordinary carbonium ions. However, as already mentioned in the introduction, gas-phase data indicate that the heat of formation of CH3CH=eH is in between those of methyl and ethyl cations (2). Furthermore, the evidence just presented in the previous sections clearly indicates that vinyl cations are viable reaction intermediates. The second reason for the lack of early investigations into vinyl cations was the seemingly extreme unreactivity of vinyl halides in solvolytic processes. The unreactivity of vinyl chloride, for instance, even in the presence of silver nitrate, has been almost a legend in organic chemistry (102). This lack of reactivity of simple alkylvinyl halides has been attributed to the low stability of simple vinyl cations or to the very strong carbon-halogen bond, or both. The unusual carbon-halogen bond strength in vinyl halides compared to saturated alkyl halides has been ascribed to partial double-bond character (103, 104) coupled with increased o-bond strength (105) due to differences in

n p.

R,C=CR-X:

..

e b R,C-CR=X:

..

hybridization between alkyl halides (sp3) and vinyl halides (sp2). In fact, the C-C1 bond in vinyl bromide is shortened from 1.91 to 1.86 A and in vinyl chloride from 1.76 to 1.69 A (1 06). Besides differences in reactant stability as well as differences in the stability of the intermediate ions, there may also be other reasons, such as differences in solvation and differences in backside nucleophilic assistance, for the large discrepancy in reactivity between alkyl halides and vinyl halides. This seeming unreactivity of vinyl halides in solvolytic processes and the lack of availability of more reactive precursors, such as sulfonate esters, until recently has discouraged early attempts a$ mechanistic investigations of vinyl cations generated by solvolyses. However, vinyl cations have been generated via vinyl diazonium ions derived from various precursors.

PETER J. STANG

244

TABLE Summary of Triple-Bond and Allenic Participation

T, "C

k , sec-'

Substrate

Solvent

CH,C%CCH,CH,X

HCOOH, NaOOCH

60

-

CH,C+CCH,CH,OTs

CF,COOH, NaOOCCF,

50

-

RCXCH,CH,OSO,C,H,NO, R = Me, Et, i-Pr

CF,COOH, NaOOCF,

50

RCXCH,CH,OSO,C,H,NO, R = Me, Et, i-Pr

CF,COOH, Hg(OAc),

50

-

CH,C%CCH,CHOSO,C,H,NO,

CF,COOH

50

-

CH,C=CCH,CH, Br CH,~CCH,CH,OSO,C,H,NO,

1

CH,

~

VINYL AND ALLENYL CATIONS

245

VI in Solvolysis Involving Vinyl Cations

AH$ kcal/mol

AS'

kcal/mol

Main products

Ref.

0

C H J 4 \

CH3

20 %

15

1%

0

II

CH,C=CCH,CH20CH

+ olefin

CH3C=CCH, CH, OH

i5

CH ,C=CCH,CH ,OAc

71

0 C H , t d 85 %

71

9%

0

II

R - C d

ao

R = Me, Et, CPr

0

R - 8 4

71

R

R

Me

%

3 Et 10 i-Pr 25

15

CH,C=CCH,CHOCCF,

w 0

0 25 %

15%

9 0

78

PETER J. STANG

246

Table VIT, "C

k, sec-I

Substrate

Solvent

CH,CXCH,CHOSO,C,H,NO, I CH3

2 : 1 H,O : acetone

50

EtOC%CCH,CH,OTs

50% aq. acetone

55

-

HCOOH, HCOONa

75.0

3.0 x

CH, I CHM(CH,),CHOTs

0 II CF,CO,H, NaOCCF,

25.0

2.7 x

CH 3 I CHM(CH,),CHOTs

HOOCH, NaOOCH

25.0

2.7 x lo-'

HOAc, NaOAc

70.0

3.2 x

CF,COOH, NaOOCCF,

25.0

3.0 x 10''

HOOCH, NaOOCH

25.0

9.8 x lo-'

CH 3 I

CH, CX(CH,) ,CHOTs

24 I

VINYL AND ALLENYL CATIONS (continued) AH*

ASS

kcal/mol

kcal/mol

-

-

Main products

Ref.

I CH-,CZCCHz CHOH

78

90 %

10%

0 -

II

Et0C-a

78

EtOCO(CH2),-O--(CH2)3CO2Et

60 %

0

II

CH,CH,CCH=C(CH,),

81 CH,

I

CH=C(CH,), 6HOOCCF3 + elimination

-

91 %

82

2% CH3

I

CH=C(CH,), CHOOCH

-

40%

+ elimination

82

38 % CH3

I

CH=C(CH,), CHOAc + elimination

-

27 %

-

-

82

54 %

CH3 0

I

II

CH,C=C(CH,),CHOCH

82

+ elimination

PETER J. STANG

24 8

Table VISubstrate

Solvent

T, " C

FH 3 CH, G C ( C H J$HOTS

HOAc, NaOAc

70.0

C,H,C=C(CH2),CH,0Bs

HOAc, NaOAc

80.0

k, sec-'

9.7

3.7 x

CH,CI,, 2%CF,COOH

-70

-

CH,CI,, 2%CF,COOH

-70

-

OH

pentane : HCOOH or CH,CN, l%CF,COOH

23

-

- 30

OH

CICH, CH, C1 CF,COOH; K,CO, aq. CH,OH

0

-

VINYL AND ALLENYL CATIONS

249

(continued) AH$

kcal/mol

-

ASS kcal/mol

Main products

Ref.

CH3

-

I

CH,C=C(CH,),CHOAc 26 %

34 %

+ elimination 82

20 %

64 %

-.;x

36 %

84

70 %

84

65 %

84

R

= OCHO,

NHCOCH,

85

PETER J. STANG

250

Table VISubstrate

Solvent

a OTs

T, "C

k , sec-'

4 : 1 H,O : acetone CaCO,

I0

-

CH,COOH, NaOAc

70

-

AcOH

60

-

98%HCOOH

60

-

50% aq. acetone

60

CH,OH

60

-

80

-

HOAc, NaOAc

40.13

1.62 x lo-'

HOAc, NaOAc

39.88

2.31 x ~ O - ~

OTs

CH,=C=CHCH, CH,Br

CH,=C=CHCH,CH, OSO,C,,H,

~

CH, CH, I

I

CH,=C=CCH, CHOTs

25 1

VINYL AND ALLENYL CATIONS (continued) AH'

AS'

kcal/mol

kcal/mol

-

Main products

6

-

Ref.

+ olefin

86

+olefin

86

cis, trans

cis, trans

0

II

CH,CU

+ CH2=C=CHCH2CH20S

32%

44%

26 %

53%

83%

2%

33%

48%

-

92%

CH3

0

I

II

F C C H 3 CH2-C=CHCH2CHOH 67 %

30 %

CH, 17%cis 50% trans 22.7

--3.6

23.3

-.95

16 %

17%

AOAc i-=d+ cyclobutyl

56 %

89

89

CH2

=

+ other

87

94

12% 95

PETER J. STANG

252

Table VI-

Substrate

Fs == b o s s

Solvent

T, “ C

k , sec-’

HOAc, NaOAc

40.13

5.65 x

HOAc, NaOAc

65.0

7.35 x

HOAc

70.0

4.88 x lo-’

HOAc

70.0

1.43 x

HOAc, NaOAc

65.0

1.41 x ~ O - ~

HOAc

70.0

4.71 x lo-’

HOAc

70.0

7.50 x lo-’

HOAc, NaOAc

75.0

8.15 x

HOAc, NaOAc

57.25

3.17 x

HOAc, NaOAc

57.23

4.61 x

253

VINYL AND ALLENYL CATIONS

(contiizued) AH*

kcal/mol

21.9

AS kcal/mol

Main products

Ref.

-3.6

+ other 24.1

-11.1

+ others 22.5

34 %

-12.0 92

AcO 34 %

27 % 24.1

-5 .O

25.7

-5 .O

40%

20%

23.0

-6.8

24.7

-.18

29%

70 %

0

66% 22.8

91

45%

= =b

14%

30 %

18%

.o

19%

8 (YHzoA 8

is-"" 50 %

26.1

22 %

17%

A

c

91

&cHzo*c 17%

==

92

+ cyclobutyl

16%

-4.9 73 %

21 %

6.1 %

254

PETER J. STANG

A. Vinyl Cations via Diazonium Ions One of the first reports involving vinyl diazonium ions and possible vinyl cations is the work of Newman and co-workers (107) on the alkaline decomposition of 3-nitroso-2-oxazolidones, 132. When an aqueous suspension or 0

II

RZ 132

alcohol solution of the oxazolidone was treated with potassium hydroxide, decomposition proceeded rapidly at room temperature. The products obtained were acetylenes, ketones, aldehydes, and vinyl ethers, depending upon the substituents. When both groups in the 5 position (R, and R2)were phenyl, the product was diphenylacetylene; while acetylene was still the major product when only one group in the 5 position was phenyl and the other was hydrogen or alkyl, it was accompanied by a ketone or aldehyde, depending on the starting material. When both groups in the 5 position were alkyl, an aldehyde of unrearranged carbon skeleton was produced. If the reaction was run in absolute ethanol, enol ethers also were formed. The observed products were proposed to arise (107) via an intermediate vinyl cation, 133, formed as outlined in Scheme VIII. C=O

R

,-CH -NNO

+-

OHe

HzO

R<,C-O-CO,H R2

I

R,-CHNHNO

$ -

R< /C-OCOzH R2

I

R,-CH-N=N-OH

133

Scheme VIII. Alkaline Decomposition of 3-Nitroso-2-oxazolidones.

More recently, such vinyl cations generated by the alkaline decomposition of 3-nitroso-2-oxazolidones have been trapped by halogens t o give vinyl halides as products (108). It has been suggested that unsaturated carbenes, RzC=C:, may be the intermediates in the basic decomposition of 132 (109). Indeed, when 132 (R, = R2 = C H 3 , R3 = H) was treated with lithium ethoxide in the

VINYL AND ALLENYL CATIONS

255

presence of excess triethylsilane, a 61% yield of vinylsilane 134 was obtained (108). As carbonium ions generally abstract a hydride ion from silanes CH,

'c=c,

CH3'

>i(Et),

H 134

to yield hydrocarbons (110), the observation of 134 is good evidence for the intermediacy of unsaturated carbenes, since carbenes are known to react by insertion with the Si-H bond (1 11). The authors (108) suggest that in protic solvents, vinyl cations are involved as intermediates, whereas in aprotic solvents, unsaturated carbenes are involved in the basic decomposition of 3-nitrosooxazolidones. Recently, however, a vinyl cation, 133 (R1 = R2 = CH3, R3 = H), has been trapped by 1,2-dirnethoxyethane in the decomposition of 5,5-dimethyl-N-nitrosooxazolidone with sodium phenoxide (1 12). Vinyl cations also have been proposed as intermediates in the deamination of vinylamine, 135 (1 13). When diphenylvinylamine, ,135, was dissolved in boiling benzene and isoamylnitrite was added, diphenylacetylene formed in 5045% yield in 3-5 h . The sequence of reactions shown in Scheme IX has been proposed as a possible route to the observed product (1 13). e

(C6 H, ),C=C,

/NH2

C6H

"C=C,

,N@=NOAm

H

C,H,,

C=C-H

I

/

H

C6H5

135

Scheme IX. Proposed Mechanism of Deamination of Diphenylvinylamine (11 3).

Reaction of diphenylvinylamine 135 with nitrosyl chloride in methylene chloride at 25°C gave the following products:

135

NOCl CH,CI,

C6H

C,H,=CC,H,

13%

+

H

H\

,C6H5

>=C,

5%

-k

C1

,c=c

C,H,

6%

/C6H5

\

c1

CI I + (C6H,),CCH0

30%

15%

Attempts to intercept the diazonium intermediate 136 by addition of NOCl to 135 at -70" followed by a methanol solution of the sodium salt of 0-naphthol

PETER J. STANG

256

gave no isolable azo compound. Although the observed products in the deamination of 135 with isoamyl nitrite or nitrosyl chloride are consistent with vinyl cation intermediates, alternative mechanisms involving unsaturated carbenes and other possible intermediates may be involved and are difficult to rule out unambiguously (1 13). The decomposition of vinyltriazenes, 137, in the presence of acid has been suggested by Jones and Miller (1 14) to proceed through vinyl cations according to Scheme X. The evidence presented includes the observed products, which H

137

Products Scheme X. Mechanism of Decomposition of Vinyltriazenes (1 14).

are the vinyl esters expected to arise from the reaction of the vinyl cation with nucleophile before or after rearrangement. The amount of rearrangement observed is dependent upon the substituents and reaction conditions. For example, when R1 = p-tolyl and Rz = phenyl, triazene 137 in pure acetic acid gives about 20% rearranged product, which, however, is completely suppressed in the presence of 10 molar excess of potassium acetate. When R 1 = C6H5 and R2 = CH3, the rearranged acetate comprises 86% of the observed products, and when R 1 = C 6 H s and Rz = H , only rearranged acetate was observed besides diphenylacetylene and deoxybenzoin (1 14). This order of rearrangement is in agreement with the extent of rearrangement observed in diazotization of the analogous saturated aliphatic amines (1 15). A number of miscellaneous reactions involving diazonium ions and possible vinyl cations have been reported. Treatment of amine 138 with sodium nitrite in 20% aqueous acetic acid is reported to give methyl cyclopropyl ketone as one of four products (1 16). The reaction has been postulated to involve a vinyl cation, presumably by the following sequence of reactions (1 16):

138

Acid treatment of 139 is reported to yield acetone by the following sequence (1 17):

257

VINYL AND ALLENYL CATIONS

Finally photolysis of substituted pyrazolenines 140 in ether is reported (1 18) to yield allene 142 and diene 143 as products via vinyl cation 141.

140

141

142

143

In all of the above cases involving decompositions of vinyl diazonium ions, the observed products are consistent with a vinyl cation formulation, but extensive mechanistic studies of these reactions have not been reported. It is difficult, for instance, to establish to what extent reaction proceeds through the diazonium ion via a backside nucleophilic attack and concerted loss of nitrogen rather than through the free vinyl cation. In the absence of kinetic data, it is also difficult to rule out competing or alternative mechanisms not involving vinyl cations. Recently, stable salts of vinyl diazonium cations such as 144 have in fact been prepared (1 19, 120), but their decomposition has not so far been investigated .

144

B. Solvolysis of Aryl-Substituted Vinyl Substrates

The first genuine example of a solvolytic generation of vinyl cations was the pioneering work of Grob and co-workers (121) on substituted a-bromostyrenes

258

PETER J. STANG

145. These authors observed that in 80% aqueous ethanol, the rates were pseudo first order in bromostyrene, except for the p - N 0 2-isomer, which did not react even at 19OoC. The products of reaction in the cases where X = NH2, CH3 CONH, and CH3 0 were exclusively the corresponding acetophenones and, for X = H, 74% acetophenone and 22% phenylacetylene. Reaction rates were found to increase with solvent polarity as well as addition of silver ion, but they were independent of added triethylamine (except in the very unreactive p-nitro isomers, where in the presence of added amine, a second-order reaction ensued that resulted exclusively in p-nitrophenylacetylene as product). Br

C H z = J O x 145 X = NH2, CH,O, CH,CONH, H, NO,

In principle, vinyl substrates can react via several possible mechanisms as shown in Scheme XI. Path A represents a backside (or even possible frontside) bimolecular nucleophilic attack by solvent, lyate ion or added nucleophile, analogous to SN 2 displacements in saturated systems. Such displacements are energetically unfavorable at vinyl carbons and have so far not been observed (1 22). Path B involves a nucleophilic addition to the double bond followed by an elimination. Such a pathway, however, is very unlikely in the absence of a strong nucleophile ( I 23). Paths C, D, and E are more likely, and examples of each have been observed (124). Path C is a rate-determining electrophilic addition (protonation) in either a Markovnikov or an antiMarkovnikov direction followed by solvent capture and elimination. Path D represents a unimolecular ionization to an intermediate vinyl cation, which can react with solvent or, if 0 hydrogens are present, eliminate. Path E involves a concerted (E2) elimination with solvent acting as base and applies only to systems with /3 hydrogens. A great number of mechanistic criteria may be applied to distinguish among the later three pathways (124). The major criteria can be briefly summarized as follows. In route C, the reaction rate should be strongly dependent upon the H+ concentration of the media, and in deuteriated media there should be a reasonably large solvent deuterium isotope effect. Path E should exhibit increasing rates with increasing base concentration. Finally, in route D, the reaction rate should be independent or nearly independent of solvent pH as well as not dependent upon base concentration, and the solvent deuterium isotope effect should be small or nonexistent. It is evident that the results of Grob on the a-bromostyrene system, 145, are most consistent with path D: i.e., a unimolecular ionization and formation of an intermediate vinyl cation. Further evidence is provided by the very large effect of substituents upon the solvolysis rate, with the p-amino compound, for example, reacting some 10' times faster than the parent bromostyrene. The log

VINYL AND ALLENYL CATIONS

259

SOH Scheme XI. Possible Reaction Paths of Vinyl Substrates.

k's for the cr-bromostyrenes, 145, correlate linearly with Brown's u+ substituent constants (125) with a reaction constant of p = -6.6. However, in their original study, Grob and Cseh (121) did not investigate the pH dependence of the reaction; but Schubert and Barfknecht have investigated the pH dependence of the rate of reaction of a-bromo-p-aminostyrene (1 26). They observed that hydrolysis occurs in two stages. In strongly acidic solutions, the ultraviolet spectrum of the styrene disappears completely before the spectrum of the product ketone appears, and it is replaced by the spectrum of a metastable intermediate which slowly changes to the end product, p-aminoacetophenone. In solutions over a narrow pH range, around pH 4.5 the two stages are competitive; and in solutions of low acidity (high pH), stage two is much faster than stage one: i.e., the intermediate did not appear, and the first-order rates of styrene disappearance and ketone appearance were identical. Furthermore, the rate constant for stage one ( b b s ) is strongly dependent upon acidity, increasing

PETER J. STANG

260

linearly with [ H 3 0 f ] in media of low acidity, but leveling off in media of higher acidity. This behavior is analogous to that observed in the hydration of styrenes in general and aminostyrenes in particular (1 27). The observed pH dependence is clearly inconsistent with a unimolecular ionization and vinyl cation formation and implies reaction via hydration and path C (127). However, there is a difference of at least five orders of magnitude in reaction-rate data for a-bromo-p-aminostyrene as originally reported by Grob (121) and the data of Schubert (126, 127). This large discrepancy prompted a careful reexamination of the solvolysis of this substrate by Grob and co-workers (128, 129). First of all, they observed that although the a-bromo-p-aminostyrene is stable in solution, both the free amine and its hydrobromide salt decompose rapidly upon isolation. These authors also observed that the rate of reaction is independent of hydrogen-ion concentration between a pH of 13 and 3 but drops sharply beIow a pH of 3 (high acidity region): in other words, behavior is exactly opposite to that observed by Schubert and Barfknecht (126) and consistent with the original vinyl cation mechanism. Furthermore, in 50 vol % dioxane:H20 and dioxane:D20, the solvent deuterium isotope effect at 20" is kH,O/kD,O = 1.3. Although this solvent isotope effect is somewhat large, it is more consistent with unimolecular ionization, path D, than with rate-determining protonation, path C, where the solvent isotope effects are usually around 1.5-3.1 (130). A striking result of this reinvestigation (128, 129) is the observation that the ratio of the product ketone to the acetylene formed from a-bromo-paminostyrene is a function of the pH (Table VII) but that the rate at which they are formed is not. As the pH increases from 3.9 to 13.1, the relative yield of acetylene increases from 16% to 85%. Therefore, the acetylene formation by elimination of a proton from the vinyl cation (path b in route D in Scheme XI) is more susceptible to an increase in base strength than is ketone formation via the enol (patha). This observation is a rare case of pH control over product composition in a SN 1 -El reaction. TABLE VII Effect o f pH o n the Solvolysis Products of a-Bromo-p-aminostyrene in 50 vol% Dioxanea PH

Buffer

% p-NH, -acetophenone

% p-NH,-phenylacetylene

3.9 6.3 8.0 8.7 10.7 13.1

citrate citrate citrate phosphate borate phosphate

84 81 15 65 44 15

16 19 25 35 56 85

a

Data from (128) and (129).

VINYL AND ALLENYL CATIONS

261

It seems then that Schubert and Barfknecht (126) may have had not a-bromo-p-aminostyrene as their substrate, but some other less reactive compound, and the original vinyl cation hypothesis of Grob (121) for the solvolysis of this substrate may hold. Furthermore, Grob’s pioneering study has served as a major catalyst for further investigations into vinyl cations generated by solvolysis. Miller and Kaufman (13 1) investigated the solvolysis of triaryliodoethylenes, 146, in 70% aqueous dimethylformamide. They observed first-order kinetics X

Qf3

X

c-c

CLH,

‘I

146

147

which were independent of added nucleophile. With such trisubstituted vinyl derivatives, concerted elimination ,(path E in Scheme XI) is of course not possible. A p = -3.6 was obtained from the rates of solvolysis of the para-substituted isomers 146, Y = OCH3, H, C1, and X = H at 189.5’C. The products consisted entirely of the corresponding ketones, 147. The effect of a methoxy group in the P-phenyl ring, 146, X = OCH3, Y = H, upon the reaction rate was minimal (about 40%), which indicates that resonance contributions from the carbene species 148b are insignificant. Such / -c=c\e -c-c \ @

148a

.

@

/

148b

contributions could have arisen via transfer of an electron from the 71 system into the empty p orbital as in 149a, first suggested by Taft (132) for the phenyl cation, or by polarization of the 77 bond, as in 149b (131).

149a

149b

Added KI (.I M) was observed to cause a 40% rate depression in the solvolysis of 2,2-diphenyl-l -anisyliodoethylene, 146, Y = OCH3, X = H. Such common-ion rate depressions are indicative of relatively stable and selective intermediate cations (133).

26 2

PETER J. STANG

Similar results were observed by Rappoport and co-workers (134) in the solvolysis of various anisyl-substituted vinyl halides, 150. The rates for trianisylvinyl chloride 150, X = C1, and bromide, 150, X = Br, were found to be

150 An =p-CH,OC,H,

first order in aqueous ethanol and independent of the added base NaOH as well as of the added nucleophile sodium p-toluenethiolate (NaSC6H4 CH3-p). These data clearly rule out pathsB and C in Scheme XI and strongly support unimolecular ionization via path D. Further indication of the intermediacy of vinyl cations comes from the rate ratio of the bromide and chloride, which at 120" is kgr /kc,= 58 (1 34). The Grunwald-Winstein solvent m values (1 35) for the chloride are solvent dependent, with values of m = .42-.53, while for the bromide, m = .34. These m values are lower than expected for an SN 1 reaction (m= .7-1.0)(135): however, they were measured at 120°C and should be higher at lower temperatures (1 34). Furthermore, there is undoubtedly steric hindrance to solvation by the bulky 0-aryl groups. Indeed, for the solvent pair AcOH:80% EtOH at 120", the m value is .71 for a-bromo-p-methoxystyrene, 145, X = OCH3, and only .36-.48 for trianisylvinyl bromide 150, X = Br (1 36). Common-ion rate depressions and the involvement of vinyl cation ion pairs similar to those observed by Miller and Kaufman (131) were observed by Rappoport and Gal (136) in the solvolysis of 150 in acetic acid. Further interesting evidence for ion-pair involvement in the solvolytic generation of some vinyl cations comes from the investigation of cis- and trans1,2-dianisyl-2-phenylvinylhalides, 15 1 (1937). In 80% ethanol, solvolysis An

'c=c,

,An X

C,H( 15 l a

C6H5\

a

An

,c=c,

,An

X

151b

of 151a or 15lb is faster than equilibration of the recovered starting material, whereas in acetic acid, equilibration of the recovered starting material is faster than acetolysis (1 37). Isomerization may occur by equilibrium protonation (i.e., electrophilic addition-elimination) or by ionization to an intermediate vinyl cation ion pair and internal return to either cis or trans starting material. Rappoport and Apeloig offer the following considerations in favor of a vinyl cation intermediate rather than electrophilic addition-elimination (1 37). Isomerization (but not solvolysis) takes place with comparable rates in aprotic acetonitrile to those in acetic acid. Electrophilic isomerization should be faster

263

VINYL AND ALLENYL CATIONS

in the more acidic AcOH solvent than in 80% EtOH: however, the opposite is experimentally observed. The solvent isotope effect kAcOH /kAcOD is about 1 .I for both the solvolysis and the isomerization: a different value (138) would be expected for electrophilic isomerization. Preliminary results by Huang and Lessard (1 39) indicate that 1-halo-2-(4-morpholino)-l,2-diphenylefhenes, 152, also react via unimolecular ionization and vinyl cation intermediates. The solvolytic behavior of arylvinyl sulfonate esters also has been investigated. Jones and Maness were the first to prepare fluorosulfonate esters, 153,from the corresponding triazenes (140).In the solvolytic reactivity c6y5

/C6H5

c=c,

c-5

R1

\

OSO,R

/

/c=c \ X

152 X = Br, CI

R,

C6H5

153 R = F, CF3, p-tdyl

of vinyl sulfonate esters, besides the five possible mechanistic pathways listed in Scheme XI, there is the possibility of nucleophilic attack on the sulfonate sulfur (141). This possibility, however, can be ruled out by the inertness of aryl sulfonates under the usual solvolysis conditions (1 42). Further evidence for an S N 1 mechanism in these systems is provided by the first-order kinetics in acetic acid, which is independent of added sodium acetate, the solvent isotope effects kHOAc /kDOAc of near unity, and the solvent m value of .56 (140). An addition-elimination path also is ruled out by the 8.1 x lo4 reactivity difference between triphenylvinyl trifluoromethanesulfonate, 153, R I = C6H5, R = CF3, and corresponding tosylate, 153, R1 = C6H5,R=p-tolyl. As the inductive effects of tosylate and trifluoromethanesulfonate are comparable, such a large reactivity difference would not be expected for a rate-determining'protonation. Essentially similar results were observed by Rappoport and Kaspi (143)in the solvolysis of trianisyl tosylate in aqueous acetone. An interesting observation in the solvolysis of all arylvinyl systems is the effect of added 6-aryl groups. All triarylvinyl substrates react more slowly than do the corresponding monoaryl or diary1 systems. For example, triphenylvinyl fluorosulfonate, 153, R I = C 6 H 5 , R = F , reacts about 2.5 times more slowly (140) in acetic acid than does a-phenylstyryl fluorosulfonate, 153, R, = H, R = F. Similarly, trianisylvinyl bromide reacts 2.8 times and 1.2 times more slowly in 80% EtOH and in AcOII, respectively (144), than does cisI ,2-dianisylvinyl bromide. This difference probably results from increased hindrance to solvation and increased unfavorable steric interactions. It is clear from all of the above evidence that despite earlier doubts, vinyl cations can be generated via solvolysis and bond heterolysis, especially in cases

PETER J. STANG

264

where the resulting ion is stabilized by an adjacent aromatic system. It is well known that besides aryl groups, double bonds and cyclopropane rings also can effectively stabilize an adjacent positive charge. Hence, the next logical step in vinyl cation chemistry was the solvolytic generation of vinyl cations stabilized by such adjacent groups.

C. Vinyl- or Cyclopropyl-Substituted Vinyl Systems The solvolysis of cyclopropyl-substituted vinyl halides, 154, was first investigated by Hanack and Bassler (145) and Bergman and Scherrod (146). I

X c\H3

I

CH-C=CH,

F A = C H z

/

CH3 154

X

=

I, CI

155

Both the chloride and the iodide react within minutes at room temperature with alcoholic silver nitrate or silver perchlorate or acetate in acetic acid, yielding cyclopropyl methyl ketone and cyclopropylvinyl acetate. In contrast, the analogous iodide, 155, is completely unreactive toward silver nitrate at room temperature and undergoes silver-catalyzed conversion to isopropyl methyl ketone only slowly in a sealed tube at 150" (146). Both 154-1and 154-C1react with first-order kinetics in aqueous methanol buffered with triethylamine, at 140-160", to give cyclopropylmethyl ketone as the major product. These results were interpreted as being most consistent with the intermediacy of a cyclopropyl stabilized vinyl cation 156 (145, 146). Ion 156 is analogous to the cyclopropylcarbinyl cations, where the stabilizing effect of the cyclopropyl group is well established (147). It is also likely that analogous to cyclopropyl carbinyl system (148), ion 156 has the "bisected" structure 156a rather than the perpendicular conformation 156b.

156

156a

156b

Recently, a more detailed study of this system has been carried out, together with the behavior of 3,4-pentadien-l-yl iodide, 157 (149), a system which has previously been shown to solvolyze through ion 156 (87,91). The products of reaction of 154-1 and 157 with AgOAc in acetic acid at 25°C are given in Table VIII. The similarity of the products and their relative amounts

VINYL AND ALLENYL CATIONS

265

indicate similar or identical intermediates and were accounted for by the processes shown in Scheme XI1 (149). X [>-bCH2 157, x = I 161, X = OAc

154, X = I 160. X = O A C

qCHZ + OAc

dCHZOAC

162

163

Scheme XII. Mechanism of Solvolysis of 154 and 157.

Santelli and Bertrand (1 50) have examined the reaction of I-(I-chlorovinyl)-l,2-dimethylcyclopropane, 164, in 10 : 90 acetone:water at 55°C and obtained the following products:

13.5%

15.7%

33.2%

12.6%

8.8%

No kinetic data were given, but the products were accounted for by means of a mechanism similar to that shown in Scheme XII.

PETER J. STANG

266

TABLE VIII Products from Acetolysis of 154-1 and 157a Products, %

Substrate

ICyclopropyl-I-iodoethylene, 154

3 ,.l-Pentadien-l-yl iodide a

158 12.6

159 27

160 58.2

4.8

23

61.5

161 .97 9.4

162 1.15

163 .13

1.21

.13

Data from (149).

Stabilized vinyl cations also can be formed participation in vinyl halide solvolysis. Grob and investigated the solvolysis of a number of substituted 165. Bromodienes 165 solvolyzed via first-order rates

by allylic double-bond co-workers (1 5 1) have 2-bromo-l,3-butadienes, in 80% aqueous ethanol

165

which were independent of added triethylamine concentration. The products of reaction and their relative amounts are shown in Table IX. The relative rates in 80% EtOH at 100" are shown in Table X. The data are best explained by unimolecular ionization to mesomeric vinyl cations 166a and 166b followed by product formation as shown in Scheme XIII. OH \

I

I

/

/C=C-C=C

\

-

0

Br \

/c=c /

80% EtOH

II

I

CHC-C=C\

\

I

\

166a

Scheme XIII. Mechanism of Solvolysis of 165.

166b

/

I I

Data from (151).

H H H CH, H CH,

H H H H CH, CH,

165a 165b 165c 165d 165e 165f

a

R2

R,

Compound

CH, CH, H H H H

R,

CH, H CH, CH, CH, CH,

R,

H CH, CH, CH, CH, CH,

R,

R3

-

-

R2’

R,

0

R,

II I ,R4 CHC-C=C,

25% 21% 16% 23% 28%

Rl,

p 4

20% 16% 29% 24% 19%

Rl/GC-C=C.,

T3

Products of Solvolysis of 165 in 80% EtOHa

TABLE IX

R,’

Rl,

7, 55% 63% 55% 5 3% 5 3% 100%

R,

I

C=C=C-COEt

PETER 3 . STANG

268

TABLE X Relative Rates of Solvolysis of 165 in 80% EtOHa Compound 165b 165a 165b 165c 165d 165e 165f

k:$ -.01 1.o 1.5

535. 716. 297. 765.

a Data from (151). All R’s = H.

The importance of resonance contributor 166b is shown by the substitution pattern: methyl and gem-dimethyl substitution in the 4 position greatly enhance the rate of solvolysis by stabilizing the mesomeric ion 166b. Charge delocalization is most effective when the planes of the diene double bonds are perpendicular to each other, providing the maximum overlap between the empty p orbital on C2 and the 71 orbital of the C3,4 double bond, as required by mesomeric ion 166b. Furthermore, the allenelike structure of 166b with sp hydridization requires a linear arrangement of C1 , Cz, and C3. Hence, the bromodienes, 165, should react most readily in a nonplanar conformation. The uv absorption maxima given in Table XI indicate that considerable departure from planarity exists in bromodienes 165b, d, e, f, since the maxima are shifted

TABLE XI uv Absorption of 2-bromodienes, 16Sa Compound 165 165a 165b 165c 165d 16% 165f

bobs max? ~

229 195 227 208 215 210

~

a Data from (151). See (152).

calc b h a x

E

219 229 229 229 234 234 239

17,000 8,100 7,5 00 8,400 7,660 13,000

269

VINYL AND ALLENYL CATIONS

to shorter wavelengths by 19 to 34 nm relative to the calculated values (151) [calculated values were obtained by adding 5 nm per methyl substituent and per bromine to the base value of 1,3-butadiene (1 52)] . Further evidence for the importance of mesomeric ion, 166b, comes from a careful examination of the solvolytic behavior of the cyclic bromodienes, 167 (153). In these systems, the planarity of the diene double bonds precludes H

I

I

I

R

R

167

CH3 165e

168

overlap of the incipient empty p orbital with the 7~ bond: furthermore, the analog of mesomeric ion 166b, namely 168, cannot be linear because of ring strain. Whereas an immediate precipitate of AgBr is obtained from the acyclic butadiene 165e in ethanolic silver nitrate, no reaction occurs with the cyclic bromodienes, 165a, R = H; 165b, R = CH3, even after 1 hr at 70°C (153). Moreover, no solvolysis of 165a and 165b occurs in 80% aqueous ethanol at 180", whereas the acyclic model compound 165e reacts with a half-life of 25 min at 90" in 80% ethanol. This result confirms the hypothesis that the acyclic bromodienes derive their high solvolytic reactivity from overlap of the empty p orbital in vinyl cation 166a with the 71 system of the diene double bond, 166b (153).

D. Solvolysis of Simple Alkylvinyl Systems It is evident from the foregoing sections that simple alkylvinyl halides do not react via an SN 1 mechanism, if at all, even under extreme solvolytic conditions (146, 149). More reactive leaving groups, such as arylsulfonates, were clearly needed to investigate the possible solvolytic behavior of simple alkylvinyl systems, but the preparation of vinyl sulfonates until recently was unknown. Peterson and Indelicato (154) were the first to report the preparation of vinyl arylsulfonates via reaction of the appropriate disulfonate with potassium t-butoxide in refluxing t-butanol. They prepared and investigated the solvolysis of l-cyclohexenyl tosylate I 6 9 and cis-2-buten-2-yl tosylate 170 and the corresponding p-bromobenzenesulfonates (brosylates). Reaction OSOzAr

0

169a Ar = p-CH3C6H4 169b Ar = p-BrC6H4

H

\

OS02Ar

/

/c=c \

H3C CH3 170a Ar =p-CH3C6H4 170b Ar = p-BrC,H4

PETER J. STANG

270

of 169a and 170a with formic acid buffered with sodium formate at 59.8" gave 92% cyclohexanone and 100%2-butanone, respectively. However, in each case the tosylates, 169a and 170a, were found to be some three times more reactive than the corresponding brosylates, 169b and 170b, respectively. The faster rate of the tosylates relative to the brosylates indicates that in formic acid, reaction has occurred via rate-determining addition (protonation) followed by elimination, path C in Scheme XI, rather than SN 1 solvolysis. If solvolysis had occurred, the brosylate rate constants should have been about three times those of the tosylates (1 55). Both the cis-2-buten-2-yl tosylate and the brosylate, 170a, b, were found to be unreactive in 50% aqueous methanol, a solvent with similar ionizing power to that of formic acid (135), at 59.8" for 18 days. It therefore seemed that even such excellent leaving groups as a tosylate and brosylate are unreactive when attached to a trigonal carbon substituted with only alkyl groups. Since trifluoromethanesulfonates (triflates) are known to be at least lo4 to l o 5 more reactive under solvolytic conditions than the corresponding arenesulfonates (1 56) they are ideal leaving groups for otherwise unreactive systems (142). Triflates were first used as leaving groups in solvolysis by Hansen (157a), arylvinyl triflates were first prepared by Jones and Maness (140), and simple alkylvinyl triflates by Stang and Summerville (I 57b). Alkyl triflates 171 were prepared by the electrophilic addition of trifluoromethanesuIfonic acid to the corresponding acetylenes. R< ,OSO,R

,c=c,

R*

CH,

171 a R = C F , , R , = R , = H b R = CF,, R , = CH,, R, = H c R = CF,, R, = H, R,= CH,

The trans-2-buten-2-yl triflate 171b was shown to solvolyze in 80% aqueous ethanol at 76" (k = 6.3 x sec-') to give dimethylacetylene as the only product. The corresponding cis isomer 171c has a solvolysis rate at 76" of 2.2 x sec-' and gives 58% dimethylacetylene, 9% methylallene, and 33% 2-butanone as products. The product ratio for the cis isomer 171c did not change appreciably in the presence of a base, such as pyridine, added prior to reaction. The solvolysis rates of isopropenyl triflate 171a in 80 and 50%aqueous ethanol correspond to m = .52, a value comparable to that observed in the solvolysis of simple secondary alkyl systems, such as m = .40 for isopropyl brosylate. Compound 171a also shows a 37-fold rate acceleration in the presence of 1.1 equivalent of NaOH. A careful examination of all the data indicates a delicate balance between a concerted elimination, path E in Scheme XI, and a unimolecular ionization

VINYL AND ALLENYL CATIONS

271

involving a vinyl cation, path D in Scheme XI, for the solvolysis of alkylvinyl triflates, 171. The trans isomer, 171b, reacts at a rate 40 times that of the cis isomer, 171c, and yields only dimethylacetylene as product, which indicates that the trans isomer, 171b, because of its favorable geometry, reacts by the concerted elimination pathway. The cis isomer, 171c, which is in a geometrically unfavorable arrangement for concerted elimination, reacts by a unirnolecular ionization and a vinyl cation intermediate. The kinetic 6-deuterium isotope effects support this hypothesis. The trans isomer, 171b ( H = D), was found to have an isotope effect of k H /kD = 2.1, whereas the cis isomer, 171c (H = D), has an isotope effect kH/kD = 1.2. The former is more consistent with a primary deuterium isotope effect, indicative of bond breaking in the transition state and mechanism E (Scheme XI), whereas the latter is more like a normal 0-dueterium isotope effect (vide infra) and more consistent with a mechanism involving a vinyl cation and path D in Scheme XI (157b). Essentially similar results and conclusions were obtained by Peterson and Indelicato (1 58) in the solvolysis of the corresponding tosylates and brosylates, 171b (R=p-CH3CgH4 orp-BrC6H4) and 1 7 1 (R=p-CH3CgH4,p-BrC6Hq), ~ in 50% aqueous methanol at 130". In this case, the frans isomer was found to react at a rate 10 times that of the cis isomer. Furthermore, the frans isomer gave 95% 2-butyne and 5% 2-butanone, whereas the cis isomer gave 72% 2-butyne and 28% 2-butanone as products. Also, as expected (vide supra) for a unimolecular solvolysis reaction, the cis brosylate reacts at a rate four times that of the corresponding tosylate.

E. Structure of Vinyl Cations It is evident from the previous sections that vinyl cations are viable reaction intermediates. Nothing, however, has so far been said concerning their structure. A priori, a vinyl cation can have two possible geometries: a linear structure, 172a, with a sp-hybridized carbon and an empty p orbital; or a trigonal form, 172b, with a sp2-hybridized carbon and an empty sp2 orbital.

172a

172b

In analogy with carbonium ions, one would expect the linear form with sp hybridization, 172a, to be more stable. There are two approaches to the determination of the possible structure of vinyl cations; theoretical, by means of calculations; and experimental. The former will be discussed first.

272

PETER J. STANG

1. Theoretical Calculations With the advent of high-speed computers, it has, at least in principle, become possible to calculate the exact geometry and energy of molecules from first principles alone. Such exact calculations should necessarily rely on quantum mechanics and could be accomplished only by solving the appropriate Schrodinger equation for the desired molecular system. The difficulties and complexities involved in such detailed quantum mechanical calculations for even the simplest organic molecules are well known, and hence, alternative approaches such as the Hiickel method (1 59) and numerous self-consistent-field (SCF) methods and various neglect-of-differential-overlap procedures (1 60) have been employed, Even these simplified approaches are time consuming and relatively expensive, particularly for larger molecules: hence, most calculations on the geometry of vinyl cations have been done on the parent C2H; system. Molecular orbital calculations for the parent vinyl cation, CzH;, were first reported by Hoffmann (161), who used the extended Huckel method, and more recently by Yonezawa and co-workers (162), who used a semiempirical SCF procedure. Both treated the problem of classical, 172 (R = H), versus bridged structures, 173, but the methods suffered from their inability to account satisfactorily for bond-length changes, and neither discussed the question of linear, 172a, versus bent, 172b, structures.

173

It is interesting that NDDO calculations predict the bridged ion 173 (protonated acetylene) to be more stable by some 22 to 32 kcal/mole than the classical ion, 172a (R = H) (1 63), whereas more reliable ab initio calculations (163, 164) clearly predict the classical ion, 172a (R = H), to be more stable by 18 to 25 kcal/mole than the bridged ion 173. Figure 3 shows a plot of the energy required to bend the third hydrogen out of the HCH plane in methyl cation, as determined by ab initio calculations (165). As is seen from the figure, it clearly takes energy to deform the methyl cation from its favorable planar and trigonal geometry with an empty p orbital, which puts in more quantitative terms the organic chemist’s intuitive and qualitative feeling that carbonium ions prefer to be planar. Figure 4 shows a similar plot for the energy required, as determined by INDO calculations (163), for bending the methine CH bond out of the linear arrangement, 172a (R = H), towards the trigonal geometry, 172b (R = H). The results clearly indicate that in analogy to normal carbonium ions, vinyl cations prefer an empty p orbital and a linear geometry, 172a, over the empty spz orbital and a trigonal (bent)

VINYL AND ALLENYL CATIONS 10

~

-

I

1

I

I

I

213

-

8-

3

Y

-

5

10

15

+, degrees

Angle of bend (degrees)

30

Figure 3. Ab initio energy for deformation of methyl cation; out-of-plane deformation of third hydrogen from HCH plane (165).

Figure 4. INDO energy for bending CH bond in vinyl cation. 172a, R = H: solid line, in-plane bending; dashed line, out-ofplane bending (163).

geometry, 172b. In fact, the bent sp'-hybridized structure is some 50 kcal/mole less stable than the linear sp-hybridized form (16 3 , 164). The effect of methyl substituents is interesting; the classical linear geometry still is preferred over the hydrogen or methyl bridged structure. Furthermore, B substitution of a methyl group provides very little or no extra stabilization over the unsubstituted parent system, 172a, R = H. On the other

PETER .I. STANG

214

hand, Q! substitution (i.e., a methyl group attached to the carbonium ion center) produces a significant stabilization of 23 to 39 kcal/mole. This additional energy gain in the methyl-substituted vinyl cation is comparable to the 24 kcal/mole gain in stability upon going from n-propyl to the isopropyl cation (2a). The calculated charge distributions for the parent and the a- and &substituted vinyl cations are as follows (163): H 0,138 H\-0,014

e

0.215

C=C-H

H’

0.245

H\- 0.084 H/

- 0.232 /H0.219

c=c-c-o,339

\HH0.169

0.310

0,219

H.- I0.182 ’C

4 \0.063

H

0,152

,C=C-H

H

0.234 0,205

0.237

Finally, a recent ab initio calculation (1 66a) gives the following geometrical parameters for the parent Cz H; vinyl cation:

Extended Huckel calculations have been carried out on the 1-cyclopropylvinyl cation 156 (1 22). These results show that the most favorable conformation for this ion is the linear “bisected” structure I56a. However, Hanack et a2. (166b), by means of a modified CNDO technique, calculate the most stable geometry of the intermediate ion resulting from homopropargyl participation to be a bridged cyclobutenyl cation rather than 156a. It should be clear, of course, that all of the calculations refer to ions in the “gas phase” and may not give an accurate picture of the exact geometries and energies of these same ions in solution. The calculations cannot account for possible deviations from the ideal gas-phase structures that result from shielding effects of the departing leaving group, distortions caused by solvation, ion-pair effects, gegen ion effects, etc.

2. Experimental Approaches Experimentally, there are two approaches to the elucidation of the structure of vinyl cations: first, preparation and solvolysis of systems where because of geometric restrictions the intermediate vinyl cation by necessity is bent; and second, by a careful examination of the stereochemistry of solvolysis of appropriate acyclic substrates. Hanack, Schleyer, Stang and co-workers (1 67) recently have independently achieved the synthesis of vinyl triflates from ketones. This procedure,

VINYL AND ALLENYL CATIONS

215

together with that of Frydman (168) and Truce (169) for the preparation of vinylsulfonates, has greatly extended the scope of vinyl cation chemistry. This procedure was used to prepare cyclic vinyl triflates 174-177. The results of the solvolysis (1 70) in 50% aqueous ethanol of the cyclic vinyl triflates is given in Table XII. For comparison, the rate of solvolysis of cis-2-buten-2-yl triflate under the same conditions also is shown in Table XII. TABLE XI1

ooTf

Solvolysis of Cyclic Vinyl Triflatesa

O

Compound

O

T

f

O O T f QoTf

175

174

1 ooo k5,%EtoH sec-'

6.1 x lo-'

5.8 x

krel

3.4

3.2

176

5.5 x 10-1

lo-'

3.0 10-4

T O T ,

177 2.0 x

lo-'

1.1 x 10-5

1.8 x

1.0

a Data from (170).

Solvolyses of these cyclic vinyl triflates at 100' in 50% aqueous ethanol, buffered with triethylamine, lead exclusively to the corresponding cycloalkanones. Treatment of 176 with buffered CH3COOD gave a mixture of cyclohexanone (85%) and 1-cyclohexenyl acetate (1 5%). Mass spectral analysis of this cyclohexanone product showed that the amount of deuterium incorporation was identical to that amount observed when cyclohexanone was treated with CH3COOD under the same conditions. This result rules out an additionelimination mechanism, at least in the case of 174, and since concerted elimination is highly unlikely in small ring systems, it suggests a unimolecular ionization and formation of a vinyl cation intermediate in the solvolysis of cyclic triflates (1 70). The observed solvent m values, 174: m = .64; 175: m = .66; and 176: m = .76, are in accord with a unimolecular solvolysis. The marked effect of ring size upon the solvolysis of cyclic vinyl triflates is evident from the data in Table XII. The eight-membered and seven-membered ring systems, which are more or less capable of accommodating a linear arrangement, as required by an sp-hybridized vinyl cation, react with a rate comparable to that of the acyclic model compound, which has no geometric restrictions. In the smaller six- and five-membered ring systems, the vinyl cations are rigidly held in bent geometries. Since such bent structures are energetically less favorable than the linear ions (vide supra), the rates of solvolysis of these systems are considerably slower than that of the similar acyclic precursor. These

PETER J. STANG

216

results indicate that there is a strong preference for a linear structure, 172a, for vinyl cations, but that in especially constrained systems, such as small cyclic ring structures, bent vinyl cations, 172b, may in fact exist (1 70). A second, and perhaps more interesting, experimental approach to the elucidation of the structure of vinyl cations consists of an examination of the stereochemistry of solvolysis of cis and trans vinyl substrates. In normal carbonium-ion chemistry, reaction proceeds from a precursor with a tetrahedral carbon capable of asymmetry: hence, the stereochemistry of displacement in an aliphatic system can be ascertained by observation of the fate of the chiral center from reactant to product. An ethylenic system, of course, has no such chiral center, and hence there can be no change in optical configuration as the reaction proceeds. However, the stereochemistry of vinylic displacement and hence the symmetry and geometry of the intermediate can be

R

R2

R

Rl

./c=c t /X \

Rl

-

/c=c D \

R\: RZ

R1

1 9 0 /

SOH+

-

R

R2

0s

/

R2

\

0s

/

+ /c=c \

\

Ri

RI

c=c\

R1 Rl R, Scheme XIV. Stereochemistry of Displacement of Vinylic Systems.

Rl

211

VINYL AND ALLENYL CATIONS

ascertained from the stereochemical relationship of substituents in reactants and products. Two extremes may be envisioned, as illustrated in the top and middle of Scheme XIV. One extreme would be complete nonstereospecificity: that is, formation of the same “natural” ratio of cis and fruns products from either pure cis or pure trans precursor (top of Scheme XIV). Such a result demands a symmetric intermediate and hence a linear geometry with an empty p orbital for the structure of the intermediate vinyl cation. The second extreme would be complete stereospecificity : that is, formation of only cis products from cis precursors and trans products from trans precursors. This result would imply a trigonal vinyl cation which retains its conformation during the course of the reaction. A third possibility is formation of stereospecific bent vinyl cations, but with rapid interconversion between the two stereoisomers (shown at the bottom of Scheme XIV), and hence nonstereospecific product formation. A reasonable idea of the stability of the stereoisomeric trigonal vinyl cations can be gained from the behavior of vinyl anions and radicals. It is known that the interconversion between stereoisomeric vinyl anions is fairly slow, with an activation energy of the order of 18-24 kcal/mole (171). On the other hand, inversion of stereoisomeric vinyl radicals is reasonably rapid, even at fairly low temperatures, with an activation energy of the order of 2-8 kcal/mole (172). Hence, extrapolating from the electron-rich vinyl anion through the neutral vinyl radical to the electron-deficient vinyl cation, one would expect rapid interconversion between stereoisomeric vinyl cations and only a small amount (if any) of stereospecificity. To put it differently, the vinyl cation should be mostly linear with an empty p orbital and very little trigonal character. A number of reports on the investigation of the stereochemistry of solvolytic displacement at vinyl carbon have appeared. Rappoport and Apeloig (173) have studied the solvolytic behavior, under a variety of conditions, of cis and trans 1,2-dianisy1-2-phenylvinyl halides, 178.

,x , c=c, An An

C A ,

178a X = Br, C1

An\

c=c’

X

‘An

C,H5’

178b

An = p C H , O C , H ,

Solvolysis of either 178a or 178b in 80% aqueous ethanol in the presence of p-toluenethiolate or benzylthiolate gives a 1 : 1 mixture of cis and trans products. A 1 : 1 cis : fruns product ratio also was observed in acetic acid in the presence of either sodium acetate or silver acetate. The 1 : 1 product ratio was observed as early as 10% reaction and remained constant throughout the reaction. The acetolysis is accompanied by extensive ion-pair return, which causes cis fruns, 178a 178b, isomerization. However, this isomerization

*

*

PETER J. STANG

278

cannot be responsible for the 1 : 1 cis : trans product ratio, because the isomerization was observed to be a function of reaction time, whereas the product ratio was not. Furthermore, the equilibrium ratio of starting bromides is 37 : 63, which cannot lead to a 1 : 1 acetate ratio (173). A 1 : 1 cis : trans product ratio also was observed in formic acid. It is evident from these data that in the solvolysis of 1,2-dianisyl-2phenylvinyl halides, 178, “racemization” (i.e ., complete nonstereospecificity) is the preferred stereochemical course of reaction, regardless of the stereochemistry of the starting material, added nucleophile, solvent, and leaving group, which indicates that the resultant intermediate vinyl cation has a linear sp-hybridized geometry rather than a bent structure. However, this conclusion cannot be extended and generalized to all acyclic vinyl cations, for the vinyl cation resulting upon solvolysis of 178 has a strongly stabilizing a-anisyl group, which in order to exert its full stabilizing effect would ips0 facto necessitate a linear sp-hybridized vinyl cation. Kelsey and Bergman (1 74) have examined the stereochemistry of solvolysis of cis- 179a, and trans-1-cyclopropyl-1 -iodopropenes, 179b.

Q/c=c\

Q/c=c

F H 3

I

I

H

179a

/H \

CH3

179b

Treatment of either 179a or 179b with excess silver acetate in acetic acid at room temperature gives rise to eight products, shown in Scheme XV.

p

3

I

0

II

179a

[)-C=CCH,

+ [)-C-CH2CH3

>-( 4

+ CH3CH-C-CHCH2CH,0Ac +

dCHoA

AgOAc

179b

/CH3

/c=c \ H OAC

Q , + OAC ,c=c \CH3 +

H c\H3

\

6“ d-cH3 OAc +

OAc

Scheme XV. Products of Acetolysis of 179 (174).

The product ratios were identical within experimental error from pure 179a and 179b. The products were shown to be stable under the reaction conditions. A small amount of cis + trans reactant isomerization, 179a 179b, presumably via ion pairs and internal return, was observed; this factor, however, was ruled

*

VINYL AND ALLENYL CATIONS

219

out (174) as the cause of product nonstereospecificity. Once again, the complete nonstereospecificity of the solvolysis implies a linear sp-hybridized vinyl cation intermediate. However, this conclusion also may not be generalized to the geometry of all acyclic vinyl cations for at least two reasons. First, with the large number of products observed, it would be difficult t o detect small differences in product ratios resulting from some but not complete stereospecificity in solvolysis. In fact, in a recent reexamination of this problem (175b) with more accurate analytical techniques, small differences in stereoselectivity between cis and trans precursors, accounted for by means of partially shielded ion pairs, were indeed observed. The second reason is similar to that advanced for the solvolysis of the aryl system 178: namely, the intermediate ion resulting from 179 is most stable in a “bisected” conformation analogous to the cyclopropylcarbinyl cation, and hence is preferably linear. [See, however, (I 22).] Recently Kernaghan and Hoffmann (1 75a) have investigated the stereochemistry of reaction of cis and trans I-phenylethenyl bromide, 180. Upon stirring of 180a or 180b with silver trifluoroacetate in isopentane at room

180a

180b

temperature, they observed phenylmethylacetylene (5367%) and a mixture of isomeric cis and trans vinyl trifluoroacetates. Starting from either pure 180a or 180b, there is a net retention of configuration of about 13% in the product acetates. This stereospecificity implies a bent vinyl cation intermediate and is the first such example in an acyclic system. However, the reaction conditions used are highly unusual. They are clearly heterogeneous and metal catalyzed, with reaction taking place mostly at the interphase. The ions generated under these conditions are most likely held in some sort of tight lattice with special properties. It is therefore difficult, if not impossible, to extrapolate the significance of these results to unencumbered vinyl cations generated under more normal solvolytic conditions. Recently, Bergman et al. (1 75b) have observed stereoselectivity in the solvolysis of cis and trans 2,3-dimethyl-2-hepten-2-yl triflates, 181a and 181b, in dry trifluoroethanol buffered with 2,6-lutidine at 60’. Solvolysis of 181a gave 15.2% and 70.6% of the corresponding cis and trans vinyl ethers 181c and 181d, respectively, together with 14.2% of I-methyl-I-n-butylallene; whereas 181b gave 23.9%cis and 58.6% rruns ethers 181c and 181d, respectively, along with 17.5% of the allene. This result corresponds to a translcis product ratio of 4.6 for solvolysis of the cis isomer 181a and 2.4 for the trans isomer 181b, which indicates a clear stereoselectivity with inversion of configuration. However, these

2 80

PETER J. STANG

results do not require a bent vinyl cation as an intermediate, for they can be accounted for by means of ion pairs, where the side of the molecule from which the triflate group is leaving is partially shielded from solvent attack (175b). CH3(C\H2)3

,,OTf

/c=c \

CH3

181a

CH3

-

-

zTf e

CH3(C\H2)3

/

CH3(CH2)3 >=C( CH3

C=C-CH3

CH3

OCHICF,

181d

I/

CH3(C\H2)3

/C sC-CH CH3

CH3

3

\

+

CH3(Cy2)3 C=C=CH2 /

CH2

Finally, it should be pointed out that it may be very difficult, if not impossible, to distinguish experimentally between rapidly equilibrating bent vinyl cations and a linear geometry. In particular, it may be very difficult to ascertain whether a linear vinyl cation represents a transition state with a very low activation energy (say of the order of 1 to 2 kcal/mole) between two very rapidly equilibrating stereoisomeric bent vinyl cations or whether it is a genuine intermediate of significantly lower energy than the corresponding stereoisomeric bent species. Bergman and Kelsey (174) estimate a lower limit for the stereoequilibration rate constant between the ions resulting from 179a and 179b of about 10" to 10" sec-', a rate rather close to that of a molecular vibration of 10" to l O I 3 sec-I. Indeed, it seems that if a bent acyclic vinyl cation will ever be observed, it will have to be a simple alkyl substituted vinyl system, not stabilized by an adjacent aryl or cyclopropyl group, generated at low temperature and probably under special conditions.

F. Rearrangements of Vinyl Cations

.

One of the most characteristic properties of carbonium ions is their great tendency to undergo rearrangements. These rearrangements include 1,2-alkyl shifts, hydride shifts, cyclopropylcarbinyl rearrangements, Wagner-Meerwein rearrangements, and others.

VINYL AND ALLENYL CATIONS

281

Rearrangements involving vinyl cations can be classified in two broad categories: (a) rearrangement to the double bond (182a-+182b) and (b) rearrangement across the double bond (1 83a + 183b). R \

@

-c-c=c /

/

\

-

R I

\"

c-c=c\/

/

182a

182b

183a

183b

1. Rearrangements to the Double Bond

Solvolysis of 1-t-butylvinyltriflate, 184, at 80" in 80%aqueous ethanol buffered with pyridine gave five products, as shown in Scheme XVI (176). OTf

I

(CH,),C-C=CH, 184

CH3

I "

CH3-C-C=CH2 I

-

0

1 I

+ (CH,),C-C-CH,

(CH,),C-C=CH

CH3 185

187

188

1 CH, CH,

I

*C-C-CH, I CH3 186

CH, CH,

cy3

---+

Hc\

H2C

cI

+

I

I

RCH2 C2H,0C-C-CH2

CH 3 189

I

CH3 190

CH, CH3

I

I

+ HOC - C=CH2 I

CH3 191

Scheme XVI. Solvolysis of triflate 184.

As indicated in this Scheme, triflate 184 presumably ionizes to vinyl cation 185, which can eliminate a proton and give acetylene 187 or react with solvent to give pinacolone 188; it can also undergo a methyl migration to give the tertiary

PETER J. STANC

282

carbonium ion 186, which accounts for the 2,3-dimethylbutadiene 189, 3ethoxy-2,3dimethyl-l -butene 190, and 2,3dimethy13-buten-2-01 191 observed. Similar results were observed in the electrophilic additions to t-butylacetylene (see Sec 11.3). So far, no detailed investigation of this rearrangement has been reported. Therefore, it is difficult to ascertain whether migration of the methyl group and ionization are synchronous or occur stepwise. Since the rate of solvolysis of 184 is only three times that of isopropenyl triflate (176), it seems that ionization and rearrangement are nonconcerted, for a greater rate acceleration would be expected if reaction occurred via anchimeric assistance. The solvolysis of 1-adamantylvinyl triflate, 192, reported by Hanack, Schleyer, Stang, and co-workers (1 77) also leads to rearranged products, as shown in Scheme XVII.

D

?

T C-CHZ f

-D;

C=CH2

-@

e

CHI

192

D

C

I93

194

/ Is

C

H

D

!

-

C

H

I3 CHI

195

196 Scheme XVII. Solvolysis of triflate 192.

197

The rearrangement is markedly solvent dependent. In 60% aqueous ethanol, the products are 90% adamantylacetylene, 195, and 10% adamantyl methyl ketone, 196. The acetylene could arise via an E2 elimination or via ionization and loss of a proton. In 90% aqueous trifluoroethanol buffered with lutidine, a more polar and less nucleophilic solvent, rearranged products predominated, with 69% of the homoadamantyl acetate 197, R = CH2CF3 and only 25% of the unrearranged acetylene 195 and 7% of the ketone 196. Presumably the homoadamantyl product 197 arises from 194 via a 1,2alkyl shift in vinyl cation 193. Once again, it is not possible to tell whether ionization and rearrangement are

VINYL AND ALLENYL CATIONS

283

concerted or nonconcerted. However, there must be considerable driving force for the rearrangement 193 + I 9 4 since there is n o rearranged product observed in a variety of solvents in the solvolysis of 1-adamantylmethylcarbinyl brosylate, the saturated analogue of 192 (178). 1,2-Alkyl shifts also occur in the solvolysis of alkyl-substituted cyclic vinyl triflates (1 70). Whereas cyclohexenyl triflate gives only cyclohexanone as product upon solvolysis in buffered 60% aqueous ethanol, 2-methylcyclohexen-1-yl triflate, 198, gives 60% ring-contrac’ted products 201 and 202. -yl triflate, 203, gives, besides 15% of an Similarly, 2,3-dimethylcyclohexen-l unidentified product, 35% ring-contracted ketone 204 and 50% unrearranged product, as shown.

aoTf6 60%EtOH,

100%

198

200

199

CH3

I

/

0

201 50 %

H 3 C 6 0 T f

------+

H 3 C 6 0+

6

CH3 0 11 C-CH,

OEt

202 10%

+ unidentified product

203

50 %

204 40%

15%

As these results show, 1,2-shift only occurs if there is a substituent on the double bond. In such a case, rearrangement can lead from a bent secondary vinyl cation, 199, t o a more stable linear secondary vinyl cation, 200, whereas in the absence of a double-bond substituent, a similar 1,2-alkyl shift would lead to an unstable “primary” vinyl cation. Interestingly, triflate 205 reacts only by methyl shift and shows no ring-contraction. On the other hand, triflate 206 reacts via

PETER J. STANG

284

ring enlargement. Preliminary rate results seem to indicate that anchimeric assistance is not involved in these rearrangements (1 70).

205 SO% EtOH

0 0

H3C CH,

&CH3 38 %

+

H3C CH3

+

15%

+

O O E t

+ unidenfified product

&H3

OEt 19 %

18%

12%

+&

a%MeOH

___)

206

CH3

93 %

7%

2, Rearrangements Across the Double Bond Rearrangements across the double bond in vinyl cations (1 83a + 183b) have been extensively investigated by Modena and co-workers in the solvolysis of 1,2-diaryl-2-arylmercaptovinyl-2,4,6-trinitrobenzenesulfonates, 207.

207

A unimolecular ionization was shown to be the mechanism of solvolysis by means of rate studies, solvent effects, salt effects, and structural effects (179, 180). The products of reaction consist of benzo [b] thiophen derivatives 209 or nucleophilic substitution products 210, depending upon the solvent system employed. By means of a series of elegant studies, Modena and co-workers have shown that the intermediate ion 208 can have either the open vinyl cation structure 208a or the cyclic thiirenium ion 208b, depending

285

VINYL AND ALLENYL CATIONS

207

-

208

- a;: 209

Ar 208a

208b

upon the exact structure of the starting material and reaction conditions. Evidence (180) for structure 208b comes from the observed substituent effects: a rho of only -2.8 is observed for substituents in the a ring (207, Y = p-CH3, H, etc.) compared to rho values of -3.5 to -4.8 for the solvolysis of various arylvinyl systems (see Section 1V.B.). On the other hand, the rho value for substituents in the 0 ring (207, Z = p-CH3, H, etc.) is p = -1.25, considerably larger than the 0-substituent effects ( p -.6) in the solvolysis of triaryl halides. These results indicate that even in the transition state leading to 208, considerable charge is delocalized from the a to the 0 position. This idea is further substantiated by the effect of substituents in the arylthio group (207, X = p - C H 3 0 , H, etc.) with a rho value of -1.5 (180). Further evidence for neighboring sulfur involvement and ion 208b in the solvolysis of 207 comes from the investigation of the stereochemistry of the products and the observed rearrangements (181). Solvolysis of ester 21 1 in 4 : l acetone:methanol at 25” gave only one geometric isomer, 212, as product.

\

CH, 21 1 TNB = 2, 4, 6-trinitrobenzene

CH

212

The complete product stereospecificity (presumably “retention”) observed in this case is in strong contrast to the complete nonstereospecificity observed in

286

PETER J. STANG

the solvolysis of vinyl substrates without P-thio substituents (see Section IV.E.2.) and argues against an open vinyl cation 208a and for 208b. Evidence for migration of the arylthio group across the double bond comes from C-14 labeling studies on ester 213 and product studies from unsymmetrical vinyl sulfonates 214 (181). Complete scrambling of the C-14 CH 3 C6H4\

Q

C=C\ ,OBs

,c=c

ArS/

Ar S

C6H5\

,OSO,TNB

/C =c

,OSO,TNB

Q

ArS

\

CH3

C6HS

214a

213 C* = I4C

214b

label was observed between the two ethylenic carbons in the reaction products derived from the solvolysis of vinyl brosylate 213 labeled in the ct position. Mixed products (i.e., 215a and 215b) were obtained in the solvolysis of either 214a or 214b vinyl sulfonate in 4:l acetone:methanol at 25" (181).

CH3

215a

215b

Anchimeric assistance in the solvolysis of P-arylthiovinyl sulfonates was demonstrated by means of kinetic studies on model compounds (182). In a variety of solvents ranging from nitromethane and methanol to acetic acid, the P-arylthiovinyl sulfonate 216 was shown t o react 20 t o 33 times faster than the triphenylvinyl sulfonate 21 7. Different accelerating factors were

217

216

H

\c=c;

C6HSS'

OSO,R C6H 5

218

/ OSOzR

H3C\

C,H,S

/c=c\

C6H5

219

observed for esters 2 18 and 219 (183). Vinyl ester 218 reacted 60% slower than model compound 217, whereas vinyl ester 219 reacted 330 times faster in a mixed solvent of 19:l CH3N03 :CH30H at 25'. Moreover, in the case of ester 218, substituents in the (Y ring give a rho value of -4.8 and substituents in the

287

VINYL AND ALLENYL CATIONS

ring bearing the sulfur a rho of -0.9, in contrast to the values observed in the solvolysis of ester 207 (vide supra). The relative anchimeric assistance factors and the different substituent effects for 216 (or 207), 218, and 219 indicate that 0-sulfur assistance in the solvolysis of 0-arylthiovinyl sulfonates is a function of the second 0 substituent R and increases in the order H < C6H5 < CH3 (183). This increase corresponds to a change of the transition-state geometry from a nearly linear vinyl cation 220a when R = H to a bridged thiirenium ion 220b when R = CH3 or C6H5. R\

C ,

@

=C-

R\

Ar

c=c /

Ar

\"/ S

Ar S

I

Ar 220b

220a

Recently, anchimeric assistance was also reported in the solvolysis of dialkyl-0-thiovinyl sulfonates (1 84). In particular, vinyl ester 221 reacts 3.8 x lo4 times faster and vinyl ester 222, 4.2 x lo3 times faster, respectively, than model compound 223 in 9:1 C H 3 N 0 3 : C H 3 0 H at 25". The large anchimeric effects, l O3 to l o 4 , in the solvolysis of dialkyl-0-thiovinyl sulfonates CH

OS0,TNB

xc=c<

CH,S'

CH,

CH

'c=c:

C, H,S'

OS0,TNB

CH,,

CH,

CH,'

,OSO,TNB

c=c,

CH,

a

221

222 TNB = 2,4,6-trinitrobenzene

223

relative to those of diaryl-0-thiovinyl or a-aryl-0-thiovinyl sulfonate, 20 to 330, indicate that the thiirenium ion intermediate is much more stable than the open vinyl cation in the alkyl systems relative to those of the corresponding aryl systems. Rearrangement across the double bond and possible anchimeric assistance involving carbon also has been investigated. Rappoport and Gal (1 34) have reported that the solvolysis of 1-anisyl-2,2-diphenyl bromide, 224, in aqueous ethanol as well as in formic acid gave &,a-diphenyl-p-methoxyacetophenone, 225, as the only product: i.e., no rearrangement product 226 was observed. 0 dBr

C6H5

k = C C6Hf

II (C,H,),CHCC,H,OCH,

QOCH,

224

225

0 F 6 H 5

-p

C,H,-Cq-H C,H,OCH,-p

226

This observation is consistent with the formation of the same 1:l cis:trans

PETER J. STANG

288

acetate mixture as product from the acetolysis of either cis-, 178a, or trans-I ,2-dianisyl-2-phenylvinyl halides, 178b (See Section 1V.E.) (1 73). Further evidence for the absence of rearrangement and 0-aryl participation in the solvolysis of triarylvinyl systems comes from the fact that the cis- and trans- 1,2-dianisy1-2-phenylvinylbromides 178a and 178b solvolyze at virtually identical rates (185) in 80% aqueous ethanol, acetic acid, and SO% acetic:50% formic acid. Since a p-methoxyphenyl group is more capable of anchimeric assistance than a phenyl group and since presumably participation preferentially occurs from a trans coplanar arrangement, if there had been participation and rearrangement in the 1,2-dianisy1-2-phenylvinylsystem, the trans isomer, 178b, should have reacted considerably faster than the corresponding cis isomer, 178a. Perhaps it is not unexpected and surprising that there is no 0-aryl participation in the solvolysis of triarylvinyl substrates, as the intermediate vinyl cation is especially stable because of charge delocalization into the a-aryl ring and has no need for extra stabilization. Interestingly, no rearrangement was also observed in the solvolysis of the trialkylvinyl substrate 227 (177). In 80:20CH30D:Dz0 or 60:40 OTf CH3,,c=c, f CH3 CD,

227

0 II (CH3),CDC-CD3

0 I1 F D , CH ,C--C
228

229

CD3COCD3:Dz 0, besides about 20% of allene, the sole product was the unrearranged ketone 228, with n o detectable amounts of 229. Presuyably in this case the 0-methyl group is not an adequate migrating group for participation and rearrangement. The first example of a carbon migrating across a double bond of a vinyl cation generated by solvolysis was reported by Hanack, Schleyer, Stang, and co-workers (1 77) with the vinyl substrate 230. Solvolysis of 230 in 80%aqueous ethanol gave, besides a small amount of allene, exclusively the rearranged ketone

230

23 1

231 as product. Similar rearrangements have of course been observed in the decomposition of certain vinyl diazonium ions. (See Section 1V.A.) Two questions regarding such a migration across the double bond can be asked. What is the stereochemistry of the rearrangement: i.e., is it the substituent that is trans or the one cis to the leaving group that migrates? Is the

VINYL AND ALLENYL CATIONS

289

rearrangement concerted (synchronous ionization-migration) or nonconcerted (for example, step wise: first ionization to a free vinyl cation, then rearrangement)? In order to answer these questions, Stang and Dueber (1 86) investigated the solvolysis of the stereoisomeric cis and trans 1,2-dimethyl-2-phenylvinyl triflates 232a and 232b, R1 = Rz = CH3. In 60% aqueous ethanol buffered with

232a

2321,

pyridine at 75", the cis isomer 232a, R2 = R 1= CH3, gave 34% 3-phenyl-2whereas the trans isomer 232b gave butanone and 66% 1-methyl-I-phenylallene, 82% ketone and 18%allene as products. In the same solvent at loo", the trans compound 232b reacts I 7 times faster than the cis isomer 232a, R1 = Rz = CH3. As the vinyl sulfonate system 232 is degenerate t o rearrangement, deuterium labeling was employed to measure the extent of phenyl migration. The results are shown in Table XIII. As the data in Table XI11 indicate, in the trans case, rearrangement is 97% stereospecific: however, rearrangement also takes place in the cis isomer, but with a stereospecificity of only 64%.Therefore, the faster rate of reaction of the TABLE XI11

Extent of Rearrangement in Solvolylis of 232a

CD, 0

Compound

CD,, Ph/

I II PhCH C-CH,

CH,O I II PhCH C-CD,

51.5 f .I%

48.6 f .I%

41.6 f .3%

52.3 f .3%

65.5 f .4%

34.5 f .4%

34.5

65.4 f .4%

,OTf

c=c,

CH, CH,,

P T f

/c=c,

Ph

CD,

Ph,

c=c,P T f

CDa'

CH,

Ph,

,c=c,

CH, a

,OTf CD,

Data from (186).

f

.4%

PETER J. STANG

290

trans isomer, the difference in product formation, and the greater stereospecificity of rearrangement in the trans isomer indicate that the trans isomer 232b reacts via participation and a bridged intermediate 233a, whereas the cis

isomer 232a reacts via the open ion 233b. The kinetic deuterium isotope effects observed (187) and shown in Table XIV lend support to this hypothesis. TABLE XIV Kinetic Deuterium Isotope Effects in the Solvolysis of 232a kH/kD(10O0, 60% EtOH)

Compound ,OTf

CH3,

c=c,

Ph'

1.17 CD3

CD3,

OTf

Ph

CH3

,c=c, /

Ph,

1.04

,OTf

p=c,

CH3 Ph,

CDf a

1.47 0

3

,OTf

c=c,

0.90

CH, Data from (187).

Two salient features emerge from the data in Table XIV. The 0-deuterium isotope effect (a-CD3 group) in the cis isomer is very much larger, k H / k D = 1.47, than in the corresponding trans isomer, with k H / k D = 1.17, which indicates a greater charge concentration in the a-position of the cis isomer and ion 233b and a considerable charge delocalization into the phenyl ring in the trans isomer, consistent with an intermediate ion 233a. (However, it is difficult to ascertain exactly how much of the isotope effect in the cis isomer results from a real 0-deuterium effect and how much from a small contribution from a

VINYL AND ALLENYL CATIONS

291

primary isotope effect resulting from allene formation.) Secondly, in the cis isomer, the y-deuterium isotope effect (P-CD, group) is inverse, as expected for an open ion of the type 233b, whereas in the trans isomer, the y-deuterium isotope effect, although small, is positive, which indicates some charge delocalization into the 0-carbon in the transition state, leading to intermediate 233a. Molecular orbital calculations show (188) that spirarenes of the type 233a are stable. Ion 233a is the unsaturated vinyl cation analog of the well known phenonium ion (1 89). Finally, participation by a remote double bond in the solvolytic generation of a vinyl cation has also been observed recently (190). Solvolysis of cis and trans triflate, 234a and 234b, in trifluoroethanol buffered with lutidine gave, besides acyclic products, 20% cyclic products 235abc in the case of the cis triflate 234a and 35% cyclic products in the case of the trans isomer 234b (190). Tf$H3

H3*CH3 OTf

234a

234b

235b

&CH3

CF3CH20 235a

23%

G. Kinetic Deuterium Isotope Effects Similarly to the deuterium isotope effects observed in the solvolytic generation of normal carbonium ions (191), there may be two kinds of deuterium isotope effects, a and 0,in the solvolytic generation of vinyl cations. However, unlike the effect with carbonium ions, there may be two different kinds of 0-deuterium isotope effects in vinyl cations: one where the deuterium is 0 to the leaving group on the unsaturated carbon 236a and one where it is 0,but on an adjacent saturated carbon, as in 236b. In the former case, a further distinction can be made on the basis of the stereochemistry of the p-deuterium substitution on the double bond, with the deuterium trans or cis to the leaving group. I

X I

-c-c=c I

,H(D) '

236a

236b

PETER J. STANG

292

Since substitution of a deuterium for a hydrogen a to the leaving group (i.e:, .on the carbon bearing the leaving group) would be a “primary” vinyl system and the resultant intermediate a “primary” vinyl cation of unusually high energy, such intermediates have so far not been generated solvolytically, and hence, to date no a-deuterium isotope effects in vinyl cations are known. Noyce and Schiavelli (21) were the first to measure a deuterium isotope effect in the generation of a vinyl cation via acid-catalyzed protonation of C6H5CEC-H and C6H5CZc--D. The observed isotope effect at 25” was kH /kD = 1 .I 1. However, this experimentally observed isotope effect is the result of a composite of two opposing effects: an a effect caused by hybridization changes and a 0 effect. The rehybridization involves a change to more p character (from sp to sp2) in the C-H bond and should result in an inverse isotope effect. In the absence of readily available experimental data, the isotope effect resulting from this rehybridization was calculated by means of the Streitwieser equation (192) to be k H / k D = .74. The 0 effect should be a normal positive isotope effect, and from the experimentally observed value of kH /kD = 1.11 and the calculated a effect of kH /kD = .74, it was estimated to be kH /kD = 1.SO (2 1). A number of kinetic 0-deuterium isotope effects in the solvolytic generation of vinyl cations have been measured. Stang and co-workers (193) observed a kH /kD = 1.43 in the solvolysis of 237 in 80% aqueous ethanol at 25”C, This effect is considerably larger than the corresponding P-deuterium Br I C,H,CHCH,(CD,)

231

238

isotope effect of kH /kD = 1.220 observed by Shiner and co-workers (194) on the analogous saturated system 238 under identical conditions. Two reasons may be offered for the enhanced 0-deuterium isotope effect in vinyl cations as compared with carbonium ions (193). As pointed out by Noyce and Schiavelli (21), in the transition state of a vinyl cation, the isotopically substituted C-H bond is ideally suited for overlap with the developing vacant p orbital, as the dihedral angle between the empty p orbital and C-H bonds is zero in the intermediate, as shown in structure 239. Shiner and co-workers (195)

Q,c: O,.H(D)

C,H,-C-&-

Q)

(pP) 239

29 3

VINYL AND ALLENYL CATIONS

have demonstrated that the magnitude of the 0-deuterium isotope effect is strongly dependent upon the dihedral angle between the empty p orbital and p-C-H bond and is at a maximum when the dihedral angle is zero. Second, in a vinyl cation, the C-C bond distance is that of C(sp)-C(sp2) and the 0-C-H distance that of a C(sp2)-H, as compared with C(sp')-C(sp3) and C(sp3)-H in a normal carbonium ion, hence shorter and closer to the developing vacant p orbital. In a vinyl cation, the 0-hydrogens on the double bond are rigidly held in the same plane as the empty p orbital, allowing for maximum hyperconjugative overlap. This overlap should result in a greater 0-deuterium isotope effect in the case where the 0-hydrogens are on the double bond, 236a, as compared to the case when they are on a saturated (adjacent) @-carbon,236b. The limited results available, shown in Table XV, bear out this expectation. If it is assumed that both cis-2-buten-2-yl triflate and cis-3-phenyl-2-buten-2-yltriflate go to a similar free vinyl cation, RCH3C=tCH3, and the differences in solvent are neglected, then the average reduction in free energy of activation per deuterium (AAFS) is about 30% higher for a P-isotopic substitution on the double bond than for isotopic substitution on an adjacent saturated 0-carbon. The discrepancy in isotope effects observed by Jones and Maness (140) and Stang et al. (193) for the solvolysis of X I C,H,C=CH, TABLE XV Summary of Kinetic p-Deuterium Isotope Effects in Vinyl Cations Generated by Solvolysis Substrate CD)K,

CH , ' C6H5, CH,'

Reaction Conditions

kH/kD

AAFSa

Ref.

80%EtOH, 100"

1.20

135

157b

60%EtOH, 100"

1.47

95

187

80%EtOH, 25'

1.43

105

193

HOAc, 66.6

1.45

250

140

,OTf

c=c,

CH

,OTf

c=c,

CH3 (CDJ

OTf I C,H,-C=CH,(D,)

OS0,F

I C,H, -C=CH,(D,)

a Average reduction in free energy of activation per deuterium in cal/mole.

294

PETER J. STANG

deserves comment. Jones and Maness, in acetic acid buffered with NaOAc, observed a k" /kD = 1.45 for one deuterium, whereas Stang et al, in unbuffered 80% aqueous ethanol, observed an isotope effect of kH/kD = 1.43 for two deuteriums, resulting in a AAF?/D of 250 cal/mole and 105 cal/mole respectively. Aside from the small difference in leaving groups, FSO; versus CF,SO;, whose effect on a limiting solvolysis should be minimal, and the temperature difference, the major difference is in the solvents employed. For reasons not clearly known, 0-kinetic deuterium isotope effects in acetic acid usually are larger than those in aqueous ethanol solvents. For example, Lewis and Boozer (196) observe a kinetic isotope effect of kH/kD = 1.40 in 80% aqueous ethanol for C2H5CDZCHOTsCD3at 58", whereas in acetic acid at the same temperature, kH /kD = 1.64. A second reason for the larger isotope effect observed by Jones and Maness (140) might be that in the less polar acetic acid solvent, there might be a small degree of E2 elimination (with solvent acting as base) superimposed o n the dominant SN 1 mechanism. Such an elimination would involve a primary kinetic deuterium isotope effect with a kH/kD Z 2 to 6 , and hence even a 1 to 5% contribution from such a pathway would have a significant effect on the experimentally observed kinetic isotope effect. Stang and Hargrove (197) have examined the effect of substituents on the kinetic deuterium isotope effects in the solvolysis of 240 in 80% aqueous ethanol at 50". The results are shown in Table XVI. The results indicate

240

that the isotope effect increases with the electron-withdrawing ability of the substituent. Presumably, as the intermediate vinyl cation is destabilized by TABLE XVI Effect of Substituents upon kH/kD in 240 Substituent, X

H P-Cl m-Cl P-CF, P-NO,

~ H I ~ D 1.40 1.44 1.53 1. I 2

1 .I1

VINYL AND ALLENYL CATIONS

295

the electron-withdrawing effect of the ring substituent, there is more need for a hyperconjugative type of stabilization from the adjacent 0-hydrogens, 239, which manifests itself in a higher deuterium isotope effect. The converse should hold for electron-donating substituents capable of stabilizing the intermediate vinyl cation. Unfortunately, so far no experimental data exist far such substituents because of the extreme reactivity of the starting substrates. However, one can take the data in Table XVI and obtain an estimated isotope effect of about kH /kD Z I .3 for p-CH3 and kH /kD 1.2 for p-CH30. Should these results obtain experimentally, it would represent an almost fourfold increase in isotope effects (from about 20% to about 80%) just as a function of substituents in the solvolysis of vinyl substrates, 240. Similar results, but with much smaller differences between substituents, were obtained by Shiner et al. (194) in the solvolysis of the analogous, substituted, saturated systems 238. A summary of the solvolysis of vinyl substrates is given in Table XVII.

V. ALLENYL AND RELATED CATIONS It is well known that allylic substrates are more reactive under solvolytic conditions than their saturated counterparts because of the delocalization of the positive charge in the developing carbonium ion over the n system and the overlap of the empty p orbital with the double bond in the intermediate ion,

241 (198). The vinyl cation analog of an allylic carbonium ion is an allenyl cation 242, where the empty p orbital on the unsaturated carbon overlaps with the perpendicular n bond of the allenyl system. Allenyl cation 242 is of course a resonance form of the well known alkynylcarbonium ion, C&-E

- e=c=c.

The solvolysis of propargylic substrates (1 99) and formation of alkynylcarbonium ions (200) has been extensively investigated. Particularly good evidence for the formation of alkynylcarbonium ions comes from the nuclear magnetic resonance spectra of alkynyl alcohols in strong acid media (200,201). The downfield shifts of -4 ppm for the proton of HCrC- and -1 ppm for CH3CE C- relative to their neutral precursors is indicative of carbonium-ion formation and shows the importance of the allenyl resonance contribution.

296

PETER J. STANG TABLE

Summary of Solvolysis Substrate

Solvent

T, "C

k, sec-I

boiling

-

25.0

-

C6H6

(C,H,),C=CHNH,

i-C,H,,NO,

(C, H,),C=CHNH,

CH,Cl,, NOCl

(C,H,),C=C(C,H,)NNNHAr

HOAc

-

C,H,OH

-

CH,C,H,SO,H

@CH,C, H,),C=C(C, H,)NNNHAr

(C, H ,),C=C(H)NNNHAr

(X = NH,, CH,O, CH,ONH, H)

: H,O

-

HOAc

-

HOAc, KOAc

-

HOAc

-

HOAc

-

80% EtOH

100.0

4.2 10-9

Et,N

I I (C, H ,)* C=C-C, H, X (X = H, OCH,, Cl)

130.5

3.44 x

@CH,OC, H,)C, H,C=C(C, H,)I

189.5

2.95 x

lo-'

291

VINYL AND ALLENYL CATIONS XVII of Vinyl Derivatives

AHSa

AS8b

rhoC

Products

Ref.

113

C, H,CH=ClC, H, cis 5%;trans 6% -

-

(C, H,),C=C(C, H,)OAc

-

-

(C, H,),C=C(C, H,)OC6 H, (65%)+ (C, H,),CHCOC, H, (35%)

-

-

(C,H,),C=C(C,H,)OSO,C,H,CH, (C6H,),CHCOC, H, (80%)

-

-

@CH,C,H,),C=C(C,H,) (OAc) (80%)+ (CH,C, H,)C, H,C=C(OAc)C,H,CH, (20%)

-

-

@CH,C,H,),C=C(C,H,)OAc

-

-

(C,H,),C=C(CH,)OAc (5%)+ (C, H,)CH,C=(C, H,)OAc (86%)

-

-

C,H,MC,H,,

(20%)+ 114

(100%)

(C,H,), C=C(H)OAc

0

-7.Rd

-6.6

X

o !-CH,

+ 22% C , H , M H when X = H

0 II

-

-

-

@CH,OC, H, )C, H,CHCC, H,

121

131

PETER J. STANG

298

Table XVII-

Substrate

Solvent

T, "C

An,C=C(An)Clf

80%EtOH

120.0

7.0 x lo-''

HOAc, NaOAc

141.5

2.9 x

80%EtOH

120.0

4.08 x 10-4

HOAc, NaOAc

120.3

6.7 x 10-I

80%EtOH

120.0

1.92 10-4

HOAc, NaOAc

120.3

2.0 x 10-5

An,C=C(An)Br

k, sec-'

I (C,H,),C=C(An)Br

(C, H ,),C=C(Cc,H5)OS0,F

HOAc

67.0

7.64 x 10-4

(C, H,),C=C(C,H ,)OSO,CF,

HOAc

67.6

1.97 x 10-3

(C,H,),C=C(C,H,)OS01CF3

90% EtOH

49.9

1.64 10-3

(C, H,),C=C(C,H,)OTs

AcOH

150.8

5.18 x 10-5

H,C=C(C, H,)OSO,F

AcOH

61.5

1.69 x 10-5

150.0

2.0 x 10-5

CI

B(!=CH,

MeOH, Et3N

-

HOAc, AgCIO, NaOAc

25.0

77.5% MeOH

150.0

AcOH, AgOAc

25.0

-

100.0 55.0

-

H,O, &NO, 10% aq. acet.

1.94 x

-

VINYL AND ALLENYL CATIONS

299

(continued)

~

H

S

~

rhoC

Ref.

Products

0 II

26.8

-14.

-

An,CHCAn

-

-

-

An, C=C(An)OAc

21.2

-20.

-

0 II An,CHCAn

-

-

-

An,C=C(An)OAc

22.3

-19.

-

-

-

-

22.6

-6.5

-

23.6

-2.0

-

-

-

-

23.8

-20.5

-

-.42

25.4

134

136

140

-

0 -

-

-

F A C H 3 OAc

-

-

-

145

D-A=CH2 0

23.3

-21.2

-

0 -

-

-

F C C H , 17.3%

+ other

-

-

-

-

146

!CHI

See text

OAc

+ F C = C H , + cyclobutyl

149

79.7 % 150

PETER J. STANG

300

Table XVIISubstrate

Solvent

T , "C

80%EtOH Et,N

150.0

k,sec-'

~~

Br I CH,=C-CH=CH, Br I CH,=C-C=C, CH,=C-C=C,

1.5 x lo-'

f~H H

f

100.0

1.55 x

100.0

3.08 x

100.0

8.24 x

100.0

1.11 x 10-3

100.0

4.61 x

100.0

1.18x 10-3

CH,

I

CH, Br

I ,CH3 CH,=C-C=C, I H CH3 Br

I

CH, =C-CH=C(CH,), H

>

Br C=;-CH=C(CH,),

CH,

80%EtOH

25.0

9.45 x

80%EtOH

25.0

1.49 x

25.0

3.67 x lo-*

50% MeOH

H,

,c=c,

CH, CH,, H

130.0

.71 x

130.0

2.71 x

130.0

7.10 x

,OBs CH,

,c=c,

,OTs

50% MeOH CH,

loe6

301

VINYL AND ALLENYL CATIONS (continued) ~~

AHS~

asSb

rhoC

Products

26.6g

-16.2

-

-M-C=C,

Ref.

/

1

\

,CHCOC=C,

20%

25%

/

1 1 ,C=C=C-COEt I 55%

\

25.6g

-17.2

-

16%

21%

63%

24.0g

-10.9

-

29%

16%

55%

23.3g

-12.1

-

24%

23%

53%

24.9g

-9.6

-

19%

28%

53%

24.1g

-9.8

-

-

-

100%

24.1

-7.1

-

-

-

-

23.8

-5.3

-

CH,MCH,

25.3

-1.1

-

C H , M C H ,, CH ,COCH ,CH ,CH, CH=C=CH 58% 33% 9%

-

-

151

151b 151b

,

I

-

158 f

-

-

-

CH,C%CCH,, CH,COCH,CH, 28% 72%

-

-

-

C H , M C H , (95%)

158

CH,COCH,CH, (5%) 158

PETER J. STANG

302

Table XVIISubstrate

Solvent

T, "C

k, sec-'

CH,=C(C, H,)OTs

50%MeOH

130.0

1.74 x lop4

0°S02CF3 60%EtOH 2,6-lutidine

100.0

1.24 x lo-*

100.0

2.15 x 10-7

74.8

1.66 x lo-'

75.2

2.18 x lo-'

OS02CF3

USozCF3 OSO2CF3

100.0

50%EtOH 1,6-lutidhe

H$

2.81 x

75.55

4.50x lo-'

75.15

3.43 x lo-'

CH3

0°s0"'F3

100.07

8.60 x

VINYL AND ALLENYL CATIONS

303

(continued)

24.2g

-

rhoC

Products

-

C,H,CX!H (37%)

33.0

-6.9

-

32.0

-3.8

-

27.7

25.7

1.1

-1.1

-

-

Ref. C,H,COCH, (63%)

158

0-o

oo

170

oo

31.0

170

26.9

50 %

35 %

0 0 ooE

H3C CH3 -1.2

-

&CH3

27.2

38 %

+ unident.

25.9 -8.2

-

18%

do

15%

H3C. CH3

19 %

170

304

PETER J. STANG Table XVII-

Substrate

Solvent

HOAc, AgOAc

I

k, sec-'

25

2.2

10-4

,,

2.0

10-3

H

dC=' \

T, "C

/

\CH3

CF, CH, OH 2,6-lutidine

CF3S0,0, ,C=CH, (CH l3C

50% EtOH

60% EtOH

60

-

60

-

50.4

6.03 x lo-'

70-85

-

HOAc, NaOAc

90%CF,CH,OH 2,6-lutidine

"

-

VINYL AND ALLENYL CATIONS

305

(continued)

AHS~ -

-

IhpC

Products

Ref.

-

See text

173

See text

175b

See text 175b See text

23.7

-4.8

-

76%

CH3

1.5%

14% 176 (CH 3)3CCOCH

2%

,CH3 (CH,),C=C(CH,)OEt HOC(CH 3 ) ,C+ CH, 1.5% 5%

17% 25%

7%

69%

PETER J. STANG

306

Table XVIISubstrate

,,

,, C6HS,

,c=c,

C6H,S

T, “C

k, sec-’

CH,NO,

25.0

3.44 x 10-4d

CH,OH

25.0

1.38 x 10-4d

HOAc

25.0

4.68 x

CH,NO,

25.0

1.54 x lo-’

CH,OH

25.0

6.8 x lo-,

HOAc

25.0

1.4 x lo-,

HOAc

140.0

3.03 x

HOAc

140.0

2.30 x 10-5

60% EtOH pyridine

100.0

1.58 x 10-3

60% EtOH pyridine

100.0

9.50 x 10-5

,OTs C6H5

(C,H,),C=C(C, H,)OTs CH,,

,OSO,CF,

c=c,

C,H5’ C6H5,

Solvent

CH,

,c=c,

CH,

,0S02CF3

CH 3 CF,CH,OH 2,6-lutidine

60.0

-

CH,=C(C, H,)OSO, CF,

80%EtOH

25.0

1.12 x

CD,=C(C, H,)OSO,CF,

80%EtOH

25.0

7.92 x lo-’

a

kcal/mole. ex.

Using Brown’s u’. Data for parent compound X = H.

VINYL AND ALLENYL CATIONS

307

(continued) Ref.

23.4d9g t2d

-2.85

22.6g

-2Sd

-

C, H, (C, H,S)CHCOC, H,

24.4g

+1.3d -

C, H (C, H S)CHCOC, HI

22.0

-11.0

-

-

-

-

24.7

-4.7

-

29.3

-6

-

26.9

-16

-

,

182

C, H, (C,H,S)CHCOC, H,

YH3

1.4

27.3

-

@\

NHCCH, (82%) I1

,C=C=CH, CH,

0

1.8

29.5

-

(18%)

66%

34%

0

-

-

186

3

L

9.9%

33.5 %

229 %

OR

190 13.1 %

10.7%

2 (49.3%) 5 (9.2%)

3 (14.4%) 6 (6.7%)

9.9% 1 (14.8%) 4 (5.8%)

-

22.4

-1.5

-

22.3

-2.3

-

C 6 H 5 M H (35%)

C,H,COCH, (65%)

193 Data for X=OCH,-p. An =p-CH,OC,H,.

E,.

308

PETER J. STANG

However, until recently n o data wer'e available on the direct generation of allenyl cations, 242, via solvolysis of suitable precursor allenyl substrates. Jacobs and Fenton (202) were the first to suggest the possible intermediacy of ion 242 in the hydrolysis of trisubstituted allenyl halides to give the corresponding propargyl alcohols as products. A detailed and elegant study of the solvolysis of a series of triarylchloroallenes, 243, has recently been carried out by Schiavelli and co-workers (203). Excellent first-order kinetics Y

a, X = Y = H b. X = CI; Y = H C, X = C H , ; Y = H d, X = C H 3 0 ;Y = H e, X = H ; Y = C H , X 243

were observed for the solvolysis of 243 in aqueous acetone and 90% aqueous ethanol, and the rates were unaffected by added triethylamine. The solvent m value for aqueous acetone mixtures is .69 for 243a and .77 for 243d. In 90% aqueous ethanol, addition of .10 M LiCl results in a 29% rate depression, while .I0 M added LiBr results in a slight rate enhancement in the solvolysis of triphenylchloroallene, 243a (203). The sole product isolated from the solvolysis These of 243a in 70% aqueous acetone at 27" is 1,1,3-triphenylprop-2-yn-l-o1. results are most consistent with a unimolecular ionization and formation of an allenyl cation 242. The relative rates of solvolysis of 243a-e in 80% aqueous acetone, shown in Table XVIII, give a rho value of p = -2.0 for substituents in the cw-ring. This value is considerably smaller than the values obtained in the TABLE XVIII Relative Rates of Solvolysis of 243 in 80%Aqueous Acetone at 250a

Substrate

k,d

242a 242b 242c 24 2d 242e

1.00

a

51

3.1 31.5

Data from (203).

3.1

309

VINYL AND ALLENYL CATIONS

solvolysis of cy-arylvinyl substrates, which indicates that there is considerable charge delocalization onto the 3 position (i.e., the alkynylcarbonium ion resonance). This result is confirmed by the similar effect of substituents in the &-ring 242c and the rings in the 3 position, 243e. Since the two rings at the propargyl end of the cation probably cannot achieve complete coplanarity, the effect of the second methyl group probably is negligible. The solvolysis of a number of alkyl substituted haloallenes, 244, also has RZ,

/

c=c=c,

X

R,

',R 244

= R, = R , = t-(CH,),C; X = C1 = R, = t-(CH,),C; R, = C,H, ;X = C1 = R, = t-(CH,),C; R, = C,H,; X = Br = R, = C,H,; R , = t-(CH,),C; X = C1 R, = R, = t-(CH,),C; R, = C,H, ;X = C1 f R, = R, = C,H, ; R, = I-(CH,),C; X = C1

a b c d e

R, R, R, R,

been examined (204). Unimolecular kinetics were once again observed in the solvolysis of 244. From the relative rates of 244b and 244c, an element effect of kgr /kcl = 56 is obtained. The solvent m values in aqueous acetone mixtures are m = 1.22 for 244a (55'), m = .90 for 244b (35"), m = 1.04 for 244c (35"), m = .95 for 244d (35"), m = 1.13 for 244e (35"), and m = .87 for 244f (35'). Again, these results strongly indicate an SNI solvolysis and formation of a resonance-stabilized allenyl cation. Unlike the triarylhaloallenes, in the case of at least two alkylhaloallenes, 244a and 244e, besides the propargyl alcohol products 245a and 245b, 20% and 5% of the corresponding unsaturated ketones 246a and 24613 also were observed in aqueous acetone. The latter products correspond to solvent attack on the allenyl cation. The mechanism of trisubstituted haloallene solvolysis may be best formulated as a rate-determining ionization to a resonance-stabilized allenyl cation, which may collapse with solvent at two different sites to give products as shown in Scheme XVIII.

245

246

Scheme XVIII. Mechanism of Solvolysis of Trisubstituted Haloallenes

An indication of the great stability of an allenyl cation relative to a vinyl cation may be gained from the fact that triphenylchloroallene, 243a, reacts in

310

PETER 3. STANG

90% aqueous ethanol at 25°C with a rate of k = 2.1 x sec-' (203), whereas sec-' trianisylvinyl chloride reacts in the same solvent with a rate of 3.5 x at 120" (134). A very crude rate factor of lo6 to lo9 may be estimated from these data for the relative solvolysis of a substituted haloallene versus the solvolysis of a substituted vinyl halide. This factor for the rate enhancement of an allenyl system over a vinyl system is considerably larger than the factor of 10' to lo2 for the relative solvolysis of an allylic substrate and the corresponding saturated system. Because of this large rate factor in favor of the solvolysis of an allenyl system, it was of interest to examine the solvolytic behavior of the unsubstituted parent allenyl halide. Stang and co-workers (205) have observed good pseudofirst-order rates for the solvolysis of allenyl bromide, 244, R1 = Rz = R3 = H, X = Br, in 50% aqueous ethanol. The observed solvent m = .44 value for the allenyl system is comparable to the .455 m value of the allylic system. No products were observed, as neither the expected propargyl alcohol nor acrolein was stable under the reaction conditions. In analogy with the solvolysis of trisubstituted haloallenes (203, 204) these results were interpreted in terms of an S N ~mechanism and ionization to an allenyl cation. However, an alternative mechanism involving the unsaturated carbene, \ ,C=C=C:, cannot be completely ruled out in the case of the parent system. Such a mechanism has been unambiguously established by a number of investigators (206-209) for the solvolysis of R,C=C=CHX or HCZC-C(R)zX in aqueous solvents in the presence of a variety of bases. Since cyclopropane rings possess electronic properties similar to those of double bonds and are capable of stabilizing an adjacent positive charge, systems such as 247 are related to allenyl substrates. Therefore, solvolysis of such

247 a R = H b R=CH,

248 a R = H b R=CH,

substrates should yield a stabilized intermediate ion 248a analogous to the allenyl ion 242. Bassler and Hanack (210) observed good first-order rates for the solvolysis of 247a, X = Br, in aqueous ethanol independent of added triethylamine. The observed solvent m value of rn = .52 is comparable to that observed in the solvolysis of similar allenyl and vinyl systems. The sole product of reaction was cyclobutanone. However, when 247b, X = C1, was solvolyzed in 70% aqueous methanol in the presence of triethylamine at 140", four products were observed (21 1): 9%of

311

VINYL AND ALLENYL CATIONS

4-methyl-1 -pentyn-4-ene, 249; 10% of 1,2-dimethyl-l-buten-3-yne, 250; 48% of 4,4-dimethyl-4-methoxy-l -butyne, 251 ; and 24% of 1,I-dimethyl-4-butyn-l-ol, 252. The mechanism of solvolysis of 247a and 247b is best explained by means of a unimolecular ionization to intermediate ion 248, which in the case of 248a, undergoes ring enlargement and, in the case of 248b, opens up to a tertiary carbonium ion shown in Scheme XIX.

H

248

241

CH3

I

1 R=CH3

@C-CH,-C=CH I

CH,

CH2-=C-CH2CsCH

I

CH3 249

,

(CH,),C=CH-C=CH 250

CH3

I

HOC-CH,C=CH I CH,

CH30C-CH2C=CH

I

CH3 251

Scheme XIX. Mechanism of Solvolysis of 247.

A summary of the solvolysis of allenyl and related substrates is given in Table XIX. As the data in this table indicate, the rates of solvolysis of allenyl bromide and 1-bromomethylenecyclopropane, 247a, are very comparable. Their rate of solvolysis, however, is about 10" slower than the rate of solvolysis of triphenylchloroallene under similar conditions. This rate difference between the parent and triphenyl allenyl system is not unlike the rate difference in the solvolysis of (C6H5)3CX and CH,X.

VI. MISCELLANEOUS Although a 1,2 hydride migration may be involved in the addition of adamantyl cation to acetylene to yield adamantyl methyl ketone (50) (see Sec. II.A.3.), no such migration has so far been reported in the solvolytic generation of vinyl cations. This fact is somewhat surprising, for hydride migrations abound in carbonium-ion chemistry and, because of the shorter C-C distance and favorable geometry in a vinyl cation, should be even more prevalent in such species. Recently, Bergman and Kelsey (212) have looked for such a 1,2 hydride

C6H5

C6H5

t-Bu H

C6H5

a

b =;c:

CH3

Calculated at 25°C. Extrapolated.

CH,

H

H5

C6H5

HS

HS

H

6'

H5

t-Bu t-Bu

6'

C,H, pCH,C,H, t-Bu

DZclBr

H

6'

t-Bu

t-Bu

t-Bu

H5

t-B u

c6

p-CH3C6H4

PCH3OCc.H4

6'

C6H5

C6H5

C64 CbH, C,Hs pCH3C,H, t-Bu

C6H5

R3

Substrate R,

pClC6 H4

R,

,

CI Br

25.0 25.0 25.0 25.0 25.0 44.8

T,"C

70%MeOH

60% EtOH

60%acetone 50%EtOH

140

25.0

25.0 25.0

50%acetone 35.2 50%acetone 35.2 50%acetone 25.0

80%acetone 80%acetone 80%acetone 80%acetone 80% acetone 50% acetone

C1 C1 C1 CI CI CI

C1 CI C1

Solvent

X

2.1 x 1 0 - ~

1.1 x lo-"

9.86 x 2.6 x

2 . 1 0 ~lo-, 1.21 x lo-, 5.23 x lo-'

4.80 x 2.76 x 1.76 x 1.80~ 1.77 x 3.75 x lo-'

k, sec-'

AH*

-

-

29.3

19.4 24.9

20.2

-

-

-

-12.4

-11.7 -23.4

-10.4

-

-

-Loa

--

-10.7 -8.8 -

-

23.4a

R,

X

see text

I1 (t-Bu),CHCC6 H, (C6H,) , C ( O H ) m B u - t

(I-Bu) ,CHC-Bu-t t-BuC, N , C ( O H ) M B u - t f-BuC, H , C ( O H ) M C , H, 0 + (t-Bu),C(OH)MC,H,

II

(C, H ,),C(OH)GCC, H, (C,H,),C(OH)C+CC,H,Cl (C,H,),C(OH)GCC,H,CH (C,H,),C(OH)CWC6H,0CH3 @CH~C,H,),C(OH)&XC,H, (t-Bu),C(OH)CeBu-t + 0

ASS em. Products

-

-

20.2 21.1

kcal/mole

R3

Summary of Solvolysis of Allenyl and Related Substrates R z \ C=C=C, /

TABLE XIX

21 1

210

204 205

204

204 204

204

20 3 203 203 203 203

Ref.

VINYL AND ALLENYL CATIONS

313

migration in the silver-catalyzed acetolysis of cis- and trans-1 -iodo-l,2dicyclopropylethylene, 253, labeled with deuterium in one of the rings. If hydride migration occurred, deuterium would be observed in both rings in the I

\

dc=cH4 CDz

253

254

255

product acetate, 254 and 255. Accurate mass spectrometric analysis of the products showed that no hydride shift occurs (<.2%) with either isomer of 253 (212), which indicates that such a process is unfavorable compared to solvent trapping and rearrangements of the intermediate vinyl cation. Other than the stabilized allenyl 242 and related 248 cations, there is also to date no report on the solvolytic generation of a “primary” 256 vinyl cation. Such species have, however, been implicated in the decomposition of some R\ ,C=C R

@

-H

256

vinyl diazonium-ion intermediates (see Sec. 1V.A.). Miller and Kaufman (21 3) investigated the behavior of some primary vinyl halides and observed that 0-bromostyrene afforded a quantitative yield of silver bromide in 30min at 100” in 80% aqueous acetonitrile. Silver bromide also was obtained in quantitative yield from 1,l -diphenyl-2-bromoethylene and l-bromo-2phenylpropene within 2 hr at 130”. In the same solvent, triphenyliodoethylene gave an 80% yield of silver iodide after 24 hr at 130”. However, in all these cases, the sole products observed were the corresponding vinyl nitro compounds, and none of the carbonyl product expected from a vinyl cation intermediate was observed (21 3). Furthermore, 1,I -diphenyl-2-bromoethylene gave 1,I -diphenyl2-nitroethylene and n o rearranged product which would be expected from a vinyl cation intermediate. Moreover, triphenylvinyl iodide, which in a vinyl cation mechanism should react fastest because of the stabilizing effect of the a-phenyl group, in fact reacted more slowly than the primary compounds. A free radical addition of NOz, generated from the thermal decomposition of AgN03, was postulated to account for these observations (213). Hence, these results confirm the unreactivity of primary vinyl halides in a heterolytic manner. Vinyl cations have been postulated as intermediates in the aqueous acetone solvolysis of 257 (214). Unimolecular kinetics were observed, and the sole products of solvolysis were the corresponding amides, 258. A rho value of about p = -1.2 was observed for the effect of substituents X and p = -.7 for substituents Y in 257. The relatively small value of rho for the aryl substituents

PETER J. STANG

3 14

257

258

on the carbon bearing the leaving group indicates that a considerable amount of charge is delocaIized to the nitrogen in the transition state and the intermediate ion. d

e

Ar,-C=N-Ar,

-

e

Ar,-C=N-Ar2

Similar results were observed in the solvolysis of 259 in 80% aqueous dioxane at 50' or 75' (2 IS). The products of solvolysis were the corresponding 0

II Ar,-C-N-NH-Ar, I Br

Ar,C-NHNHAr,

260

259

ketones, 260. First-order rates, independent of added acid, as well as common-ion rate depressions were observed for the solvolysis of 259. The rho value for substituents in Arl is p = -.92, which indicates that charge is delocalized to the adjacent nitrogen. Finally, in a recent study by Walling and El-Taliawi (216) it was shown that solvolytically generated vinyl cations may be reduced by Fel'ions in solution to the corresponding vinyl radical. When 2-buten-2-yl triflate was solvolyzed in concentrated ferrous perchlorate solution in the presence of acrylonitrile monomer, polymerization of the acrylonitrile was observed. No such polymerization occurred under identical conditions in the absence of Fe2 ions. It seems that the polymerization of acrylonitrile was initiated by the vinyl radicals formed by reduction of the intermediate vinyl cation by Fez as follows (216): +

+

- r ' -+ AoTf r+Fez+

Fe3+

I

=;\CN

Polymer

* '=\CN --

dkN

VINYL AND ALLENYL CATIONS

315

The reverse reaction (that is, the oxidation of a vinyl radical by Fe3+ to the corresponding vinyl cation) may be involved in the reaction of the dimethyl ester of acetylenedicarboxylic acid 261 with Fenton's reagent [Fez+ - H z 0 2 , (217)] (216). When 261 was treated with Fez+ -HzOz and the reaction mixture was extracted with ether, a small amount of furan 262 was isolated. A possible mechanism (216) for its formation may be addition of hydroxyl radical to the triple bond of 261, followed by addition of the intermediate vinyl radical to a second molecule of 261 and oxidation of the resulting radical with Fe3+ to the corresponding vinyl cation, followed by cyclization to 262, as shown in Scheme XX. 0 U

0

1I

CH30C-C~C-C-OCH3

+ HO*

26 1

-

CH 3OZC, C=b-COzCH3 HO'

J

C&0.

CH 3°2cHc02cH

3

CHSOZC OH COzCHo

Fe3+

CH3OzCMCO,CH3 CH302C OH COZCH,

Scheme XX. Possible Mechanism of Reaction of Fenton's Reagent with Dimethyl Acetyledicarboxylate.

Support for the involvement of Fe3+ comes from the observation that the kinetic chain length of the dimethyl ester increases with increasing concentration of added Fe3+ together with a fourfold increase in the yield of 262 (216). However, as a vinyl cation bearing carbonyl substituents may be energetically unfavorable, an alternative mechanism, involving a ligand transfer from hydrated Fe3+ ions followed by an acid-catalyzed cyclization, may be a more likely pathway: CH3OZC

-

CH3OzC )(7('OZH3

)(7(c02cH3 + Fe+3( H 2 0 ) CH302C OH C02CH3

CHaO,C

a8

COZCH,

--+H'

262

PETER J. STANG

316

Reduction of vinyl radicals by Fez+ to the corresponding anion also has been observed (2 16). When purified acetylene is bubbled through Fenton’s reagent, acetaldehyde is formed as a product, presumably via the following mechanism: HC=CH+HO*

-

.

H\ ,C=CH HO

H\

C=CH

HO’

- ’\ Fe’+

H+

-

,C=CH

+ Fe*3

HO

CH,CHO

If the oxidation of a vinyl radical by Fe3+ indeed proceeds through a vinyl cation, then these results, put together, suggest the following possibility (216):

r-

, Fe2+

. r \

? Fe’+ , -Fe2+

LB-

Such a result may have interesting biological implications, for it represents one-electron transfer processes in discrete stages, which is presumably the way oxidation-reduction reactions occur in nature.

VII. CONCLUSION AND FUTURE DEVELOPMENTS It is evident from the foregoing that vinyl cations are members of the establishment of reactive intermediates. If not geometrically constrained, they prefer to be linear in structure, with an empty p orbital, rather than trigonal. In the absence of equilibrium data between the cation and its neutral precursor, it is difficult to assign exact stabilities to vinyl cations. It is also difficult to determine exactly the relative stabilities of vinyl cations and the analogous saturated carbonium ions. The relative rates of solvolysis of vinyl substrates and their analogous saturated derivatives have been estimated to be lo6 to lo9 (131, 134, 140, 154) in favor of the saturated substrates. These rate differences, however, do not accurately reflect the inherent differences in stability between vinyl cations and the analogous carbonium ions, for they include effects that result from the differences in ground states between reactants, as well as possible differences between the intermediate ions resulting from differences in solvation, counter-ion effects, etc. The same difficulties apply in the attempt to estimate relative ion stabilities from relative rates of electrophilic additions to acetylenes and olefins, (21 S), or from relative rates of homopropargylic and homoallylic solvolysis. Perhaps the best estimates, even if only qualitative, come from the direction of protonation of allene and substituted allenes. As discussed in Section II.B.1.) terminal addition is observed exclusively in the protonation of

VINYL AND ALLENYL CATIONS

317

allene, clearly indicating that a secondary vinyl cation is more stable than a primary carbonium ion which would arise from central protonation. As expected, central protonation, resulting in a tertiary carbonium ion rather than terminal addition and a vinyl cation, is observed in the case of trisubstituted or fully substituted allenes. On the other hand, 1,3-disubstituted allenes protonate to give a secondary vinyl cation rather than a secondary carbonium ion. On the surface, this result would indicate that secondary vinyl cations are as stable as or more stable than secondary carbonium ions. However, the developing carbonium ion formed by central protonation of allene or substituted allenes has an electron-withdrawing double bond allylic but perpendicular to the developing positive charge, destabilizing the carbonium ion until it undergoes rotation. (See Sec. 1I.B.) It is difficult if not impossible to estimate quantitatively this destabilizing effect and hence accurately to assess the relative stabilities of vinyl cations and carbonium ions. Undoubtedly the most important and exciting future development in the field will be the generation of vinyl cations under conditions that allow lifetimes long enough for direct spectral observation. Such observations would allow unambiguous assignment of vinyl cations as reaction intermediates, an examination of their geometry and, by means of C-13 nuclear magnetic resonance, their charge distribution. More mechanistic work undoubtedly will be done on the stereochemistry of solvolysis, particularly of simple alkyl-substituted acyclic vinyl systems. The questions of concerted anchimerically assisted or nonconcerted rearrangements both t o the double bond and across the double bond need further development. The mechanism of reaction of “primary” vinyl triflates and the possibility of solvolytic generation of “primary” vinyl cations needs further exploration. Along these lines, an examination of the behavior of the simplest vinyl system CH2=CHOTf and the possibility of generating the parent vinyl cation needs to be done. In the proper system, under appropriate conditions, a new intermediate whch is simultaneously a carbene and a carbonium ion (i.e., a “carbenonium” ion) may be envisioned. A particularly attractive system would be 263 and 264, as promotion of an electron from the T system in vinyl cation 263a onto the

-

10

b C - H

263

263a

264

-* t-

264a

a-@263b

c--, /

P C - H

H

/

264b

318

PETER J. STANG

carbon bearing the charge would give the stable aromatic cyclopropenium cation with an adjacent carbene grouping, 263b; and a similar promotion of an electron in vinyl cation 264a would give the stable tropylium ion with an adjacent carbene functionality, 264b. Vinyl cations no doubt will be involved in more synthetic reactions and schemes, as already demonstrated by the elegant synthesis of progesterone by Johnson and co-workers (85). Novel polymerization reactions involving vinyl cations may be developed. Since cationic polymerization and vinyl polymerization (2 19) are well known processes, the future may see cationic vinyl polymerization.

Acknowledgements The author wishes to express his gratitude to Professor R. G . Bergman, C. A. Grob, P. D. Gardner, M. Hanack, G. Modena, P. E. Peterson, M. D. Schiavelli, P. v. R. Schleyer, W.M. Schubert, and C. Walling for preprints and permission to quote unpublished results, as well as numerous other colleagues for helpful discussions and suggestions. Permission by the copyright holders to reproduce Figures 1, 2, 3, and 4 is gratefully acknowledged. Financial assistance by the Research Corporation, the Petroleum Research Fund administered by the American Chemical Society, and the University of Utah Research Committee are gratefully acknowledged.

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151. Grob, C. A., and R. Spaar, Helv. Chim. Acta, 53, 2119 (1970);Tetrahedron Letters, 1439 (1969). 152. Laszlo, P., and P. J . Stang, Organic Spectroscopy Principles and Applications, Harper & Row, New York, 1971,p. 182. 153. Grob, C. A., and H. R. Pfaendler, Helv. Chim. Acta, 53, 2130 (1970). 154. Peterson, P. E.,and J. M. Indelicato, J. Am. Chem. SOC.,90,6515 (1968). 155. Winstein, S., E. Clippinger, A. H. Fainberg, R. Heck, and V. G. C. Robinson, J. A m . Chem. SOC.,78, 328 (1956);A. Streitwieser, Jr., Chem. Rev., 56, 571 (1956). 156. Streitwieser, A., Jr., C. L. Wilkins, and E. Kiehlmann, J. Am. Chem. SOC.,90.1598 (1968). 157(a) Hansen, R. L.,J. Org. Chem., 30, 4322 (1965);(b) Stang, P. J., and R. Summerville, J. Am. Chem. SOC.,91,4600(1969). 158. Peterson, P. E., and J. M. Indelicato, J. Am. Chem. SOC.,91,6194 (1969). 159. Streitwieser, A., Jr.,Molecular Orbital Theory for Organic Chemists, Wiley, New York, 1961. 160. Dewar, M. J. S., The Molecular Orbital Theory of Organic Chemistry, McGraw-Hill, New York, 1969; R. G. Parr, The Quantum Theory ofMolecularElectronic Structure, Benjamin, New York, 1963. 161. Hoffmann, R.,J. Chem. Phys., 40, 2480 (1964). 162. Yonezawa, T.,H. Nakatsuji, and H. Kato,J. Am. Chem. SOC.,90, 1239 (1968). 163. Sustmann, R.,J. E. Williams, M.J . S . Dewar, L. C. Allen, and P. v. R. Schleyer, J. Am. Chem. Soc., 91,5350 (1969). 164. Hopkinson, A. C., K. Yates, and I. G. Csijmadia,J. Chem. Phys., 55, 3835 (1971). 165. Williams, J. E., R. Sustmann, L. C. Allen, and P. v. R. Schleyer, J. Am. Chem. SOC., 91,1037 (1969). 166(a) Lathan, W. A., W. J . Hehre, and J. A. Pople, J. A m . Chem. SOC.,93, 808 (1971);(b) H. Fischer, K. Hummel, and M. Hanack, Tetrahedron Letters, 2169 (1969). 167. Dueber, T. E., P. J. Stang, W. D. Pfeifer, R. H. Summerville, M. A. Imhoff, P. v. R. Schleyer, K. Hummel, S. Bocher, C. E. Harding, and M. Hanack, Angew. Chem. Int. Ed. Engl., 9, 521 (1970). 168. Frydman, N., R. Bixon, M. Sprecher, and Y. Mazur, Chem. Commun., 1044 (1969). 169. Truce, W. E., and L. K. Liu, Tetrahedron Letters, 517 (1970). 170. Pfeifer, W. D., C. A. Bahn,P. v. R. Schleyer, S . Bocher, C. E. Harding, K. Hummel, M. Hanack, and P. J. Stang,J. Am. Chem. SOC.,93,1513 (1971). 171. Hunter, D. H., and D. J. Cram,J. Am. Chem. SOC.,88,5765 (1966);G.D. Sargent and M. W. Browne, J. Am. Chem. SOC., 89 2788 (1967); D. J. Cram, Fundamentals of Carbanion Chemistry, Academic Press, New York, 1965. 172. Kuivila, H. G., Accounts Chem. Res., I , 299 (1968);M. J. S. Dewar and M. Shanshal, J. Am. Chem. Soc., 91, 3654 (1969); 0.Simamura, in Topics in Stereochemistry, Vol. 4,E. L. Eliel and N. L. Allinger, Eds., Interscience, New York, 1969. 173. Rappoport, Z.,and Y. Apeloig, J. Am. Chem. SOC.,91,6734 (1969). 174. Kelsey, D. R., and R. G. Bergman, J. Am. Chem. SOC.,93, 1941 (1971);J. Am. Chem. SOC.,92, 228 (1970). 175(a) Kernaghan, G . F. P., and H. M. R. Hoffmann, J. Am. Chem. SOC.,92,6988 (1970); (b) T. C. Clarke, D. R. Kelsey, and R.G. Bergman, J. Am. Chem. Sac., 94, 3626 (1972); R. H. Summerville and P. v. R. Schleyer, J. Am. Chem. SOC.,94, 3629 (1972). 176. Martinez, A. G., M. Hanack, R. H. Summerville, P. v. R. Schleyer, and P. J. Stang, Angew. Chem. Int. Ed. Engl., 9,302 (1970). 177. Imhoff, M. A., R. H. Summerville, P. v. R. Schleyer, A. G. Martinez, M. Hanack, T. E. Dueber, and P. J. Stang,J. Am. Chem. Soc., 92,3802 (1970).

PETER J. STANG

324

178. See footnote 13 in ref. 177. 179. Modena, G.,U. Tonellato, and F. Naso, Chem. Commun.,1363 (1968);G. Modena and U. Tonellato, Chem. Commun., 1676 (1968); G. Cappozzi, G. Melloni, G. Modena, and M. Piscitelli, Tetrahedron Letters, 4039 (1968);G . Cappozzi, G . Melloni, and G. Modena, J. Chem. SOC.(C), 1970, 2617,2621,2625. 180. Modena, G., and U. Tonellato, J. Chem. SOC.(C), 1971, 374. 181. Modena, G.,and U. Tonellato,J. Chem. SOC.(C), 1971,381.G. Cappozzi, G. Melloni, G. Modena, and U. Tonellato, Chem. Commun., 1520 (1969). 182. Modena, G., and U. Tonellato, J. Chem. SOC.(C), 1971, 1569. 183. Cappozzi, G., G. Modena, and U. Tonellato, J. Chem. SOC.(C), 1971, 1700. 184. Burighel, A., G. Modena, and U. Tonellato, Chem. Commun.,1325 (1971). 185. Rappoport, Z., and Y. Apeloig, Tetrahedron Letters, 1817 (1970). 186. Stang, P. J., and T. E. Dueber, J. Am. Chem. SOC.,95,2724 (1973). 187. Stang, P. I., and T. E. Dueber, J. Am. Chem. Soc., 95,2726(1973). 188. Hoffmann, R., A. Imamura, and G. D. Zeiss,J. A m . Chem. Soc., 89, 5215 (1967). 189. Brown, H. C., and C. J. Kim, J. A m . Chem. SOC.,93, 5765 (1971)and references therein; C. J. Lancelot and P. v. R. Schleyer, J. Am. Chem. SOC.,91, 4291, 4294, 4296,4297 (1969);C. J. Lancelot, D. J. Cram, P. v. R. Schleyer, “Carbonium Ions,” Vol. 111, G. A. Olah and P. v. R. Schleyer, Eds., Wiley-lnterscience, New York, 1972 and references therein.

190. Clarke, T. C.,and R. G. Bergman,J. A m . Chem. SOC.,94, 3627 (1972). 191. For reviews, see L. Melander, Isotope Effects on Reaction Rates, Ronald Press, New York, 1960; F. W. Westheimer, Chem. Rev., 61, 265 (1961); Streitwieser, A., Jr., Solvolytic Displacement Reactions, McGraw-Hill, New York, 1962;E. H. Halevi, Prog. Phys. Org. Chem., 1 , 109 (1963);C. J. Collins and N. S. Bowman, eds., Isotope Effects in Chemical Reactions. Van Nostrand Reinhold Co., New York, 1970. 192. Streitwieser, A., Jr., R. H. Jagow, R. C. Fahey, and S. Suzuki, J. A m . Chem. SOC.,80, 2326 (1958). 193. Hargrove, R. J., T. E. Dueber, and P. J. Stang, Chem. Commun., 1614 (1970). 194. Shiner, V. J., Jr., W. E. Buddenbaum, B. L. Murr, and G. Lamaty, J. Am. Chem. SOC., 90, 418 (1968). 195. Shiner, V. J., Jr., B. L. Murr, and G. Henemann, J. A m . Chem. SOC.,85, 2413 (1963); V. J. Shiner, Jr., and J. S. Humphrey, J. Am. Chem. SOC.,85, 2416 (1963); V.J. Shiner, Jr., and J. G. Jewett, J. A m . Chem. SOC.,86, 945 (1964). 196. Lewis, E. S.,and C. E. Boozer, J. Am. Chem. SOC.,76. 791 (1954). 197. Stang, P.J., and R. J. Hargrove, unpublished observations. 198. DeWolfe, R. H.,and W. G. Young, Chem. Rev., 56, 753 (1956). 199. For leading references, see G. F. Hennion and D. E. Maloney, J. A m . Chem. SOC.,73, 4735 (1951); A. Burawoy and E. Spinner, J. Chem. SOC., 3752 (1954); R.S. Macomber, Tetrahedron Letters, 4639 (1970). 200. For a review, see ref. 2a, pp. 931-949. 201. Richey, H. G.,Jr., J. C. Philips, and L. E. Rennick, J. A m . Chem. SOC.,87, 1381 (1965); Richey, H. G., Jr., L. E. Rennick, A. S. Kushner, J. M. Richey, and J. C. Philips, J. A m . Chem. Soc., 87, 4017 (1965);C . U. Pittman, Jr., and G. A. Olah, J. Am. Chem. Soc., 87,5632(1965). 202. Jacobs, T. L., and D. M. Fenton,J. Org. Chem., 30. 1808 (1965). 203. Schiavelli, M. D.,S. C. Hixon, H. W. Moran, and C. J . Boswell, J. A m . Chem. SOC.,93, 6989 (1971);M.D. Schiavelli, S. C. Hixon, and H. W. Moran,J. A m . Chem. SOC.,92, 1082 (1970). 204. Schiavelli, M. D.,R. P. Gilbert, W. A. Boynton, and C. J. BoswekJ. A m . Chem. SOC., 94, 5061 (1972).

VINYL AND ALLENYL CATIONS

325

205. Lee, C. V., R. J. Hargrove, T. E. Dueber, and P. J. Stang, Tetrahedron Letters, 2519 (1971). 206. Hennion, G. F., and D. E. Maloney, J. Am. Chem. Sac., 73, 4735 (1951). 207. Hartzler, H. D., J. Am. Chem. SOC., 83, 4990, 4997 (1961);J. Org. Chem., 29, 1311 (1964). 208. Shiner, V. J., Jr., and J. W. Wilson, J. Am. Chem. Soc., 84, 2402 (1962); V. J. Shiner, Jr., and J . S . Humphrey, Jr.,J. Am. Chem. Soc., 89, 622 (1967). 209. LeNoble, W. J., Y. Tatsukami, and H. F. Morris, J. Am. Chem. SOC.,92, 5681 (1970). 210. Bassler, T., and M. Hanack, Tetrahedron Letters, 2171 (1971). 21 1. Ghenciulescu, A,, and M. Hanack, Tefrahedron Letters, 2827 (1970). 212. Private communication from Professor R. G. Bergman. 213. Kaufman, D., and L. L. Miller,J. Org. Chem., 34, 1495 (1969). 214. Ugi, I., F. Beck, and U. Fetzer, Chem. Ber., 95, 126 (1962). 215. Aylward, J. B., and F. L. Scott,J. Chem. SOC.(B), 1080 (1969). 216. Private communication from Professor C. Walling; see also G. M. El-Taliawi, Ph.D. Dissertation, Columbia University, 1972: Walling, C., G. El-Taliawi, J. Am. Chem. Soc., 93, 848 (1973). 217. Fenton, H. J. H., J. Chem. SOC.,65, 899 (1894); F. Haber and J . Weiss, Proc. Roy. SOC.(London), A147, 332 (1934); C. Walling, Free Radicals in Solution, Wiley, New York, 1957. 218. Yates, K., G. H. Schmid, T. W. Regulski, D. G. Garratt, H. W. Leung, and R. McDonald,J. Am. Chem. Soc., 95, 160 (1973). 219. Tsuruta, T., and K. F. O'Driscoll, Eds., Structure and Mechanism in Vinyl Polymerization, Marcel Dekker, New York, 1969.

Physical Properties and Reactivity of Radicals By Rudolf Zahradnik and Petr Cirsky The J. Heyrovski Institute of Physical Chemistry and Electrochemistry, Czechoslovak Academy of Sciences, Prague, Czechoslovakia

CONTENTS I. Introduction . . . . . . . . . . . . . . . . . . . . 321 A. Definitions . . . . . . . . . . . . . . . . . . . . 328 B. Preparations . . . . . . . . . . . . . . . . . . . 329 334 C. Quantum Chemical Methods . . . . . . . . . 1. SCF Methods and Configuration Interaction . . . 335 2. Simple Methods . . . . . . . . . . . . . . . . . 34 2 11. Physical Properties . . . . . . . . . . . . . . . . . . 34 3 A. Heats of Atomization . . . . . . . . . . . . . . . . . 34 3 B. Molecular Geometry: Bond Lengths and Valence Angles . . . . . . . 345 C. Spectroscopies in the Framework of One-Electronic Level . . . . . . 348 D. Ionization Potentials and Electron Affinities . . . . . . . . . . 35 1 E. Electronic Spectra . . . . . . . . . . . . . . . . . . 356 111. Chemical Reactivity . . . . . . . . . . . . . . . . . . 362 Acknowledgment . . . . . . . . . . . . . . . . . . . . 315 References . . . . . . . . . . . . . . . . . . . . . 316

1. INTRODUCTION

One of the goals of theory in chemistry is to foresee the properties of compounds unsynthesized so far and also of existing compounds, the behavior of which has not yet been examined. This goal can be achieved via a theoretical interpretation of physical properties and reactivity of compounds studied experimentally. Until now, the tool of quantum chemistry has rarely been used for predictions, while thousands of studies on inorganic and organic compounds were published confronting quantum chemical characteristics with experimental data. These studies, in particular the systematic ones, concerned predominantly the closedshell molecules in their electronic ground states. Considerably fewer papers have focused on properties of molecules in excited states (with the exception of electronic spectra) and of open-shell systems, or on the behavior of compounds in an external force field. Even when judged strictly, the studies of the first category appear to be successful enough to give us guidance in the choice of a computational method and a parameter set for actual theoretical treatments of molecules of various structural types. 321

328

RUDOLF Z A H R A D N ~ KAND PETR CARSKY

The important role of radicals and radical ions in various branches of chemistry (e.g., electrochemistry, radiation chemistry, macromolecular chemistry), their remarkable physical properties and reactivity, as well as the specific problems in a quantum chemical approach, make this region interesting from the theoretical point of view. This article is an attempt to review possibilities in a quantum chemical treatment of open-shell systems. In order to cut down the extent of this review, we disregard some problems, especially those concerning macromolecules, polymerization reactions, and open-shell transition-metal complexes. Electron spin resonance is mentioned only briefly, because it has been a topic of many reviews. A. Definitions We shall call a radical each system having one unpaired electron and of course an odd number of electrons. In terms of simple MO methods, that means a system having in its ground state one electron in the highest occupied orbital. According to the nature of that orbital, we classify u and 71 radicals. With systems having two unpaired electrons, we can distinguish a biradical and a system being in a triplet state.* t A biradical can always be expected if the highest occupied MO is degenerate and contains only two electrons: this configuration, however, does not guarantee the formation of a biradical if a distortion resulting from the Jahn-Teller effect occurs. Molecular oxygen, where the 15th and 16th electrons occupy a degenerate n*-type orbital, is representative of classical biradicals. A similar situation arises, for example, in diphenylmethane dinegative ion 1 and in conjugated systems having C3 or higher symmetry, such as systems 2 and 3.

1

2

3

Configuration interaction calculations (3, 4) indicate a possible existence of systems belonging to the second group of our classification (triplets). Although these systems have an even number of electrons and no degenerate *This distinction is formal, as in both cases the total spin is 1 and the state multiplicity corresponds to a triplet. t Hoffmann and co-workers (1) call a biradical any molecule having two nonbonding (or nearly nonbonding) MO’s occupied altogether by two electrons, regardless of the spin multiplicity. The typical feature of most such molecules is that only one VB structure can be written for them (2).

329

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

orbital, the lowest energy state is a triplet. The not yet isolated compounds 4-7 are typical representatives. Attempts at synthesis of 6 were reported recently (5). e

4

5

6

7

For a threefold degenerate MO occupied by three electrons, a configuration of a triradical having a quartet multiplicity is required by Hund’s rule. In organic chemistry, systems of this type occur rarely; but with transition element complexes, quartets, quintets, and sextets, they are common. A common feature of all of the systems considered is the presence of an open shell, i.e., a singly occupied MO; hence, they are all called open-shell systems. The radicals can be electroneutral (radicals in a narrow sense), electropositive (radical cations), or electronegative (radical anions). Radical di-ions and tri-ions are less frequent.

B. Preparations For quantum chemical estimates of radical stability and reactivity, one often needs to know the conditions and medium in which they arise. As there are many reviews on chemical preparations of radicals, we give here only a brief description of the most important preparative methods and a note on a specific problem in chemical preparations of cation radicals. Radicals can be prepared from closed-shell systems by adding or removing one electron or by a dissociative fission. Generally speaking, the electron addition or abstraction can be performed with any system, the ionization potential and electron affinity being thermodynamic measures of the probability with which these processes should proceed. Thus, to accomplish this electron transfer, a sufficiently powerful* electron donor or acceptor (low ionization potential and high electron affinity, respectively) is required. If the process does not proceed in the gas phase, a suitable solvent may succeed. Methods of general importance for radical generation can be divided into three groups: (a) chemical reductions and oxidations; (b) electrochemical reductions and oxidations; and (c) radiation methods. Alkali metal reduction is a widely employed method for the preparation of radicals derived from various classes of conjugated compounds such as hydrocarbons, heterocycles, nitro compounds, quinones, and nitriles. For

* Relative to the substrate.

RUDOLF Z A H R A D N ~ KAND PETR

330

CARSKY

references to a description of the apparatus and the procedure, we selected several instructive papers (6-10); the reaction vessel used in our laboratory is presented in Figure 1. Chemical oxidation methods (12) are less general. In a common preparation of radical cations, a solution of the parent compound is mixed with a solution of an oxidizing agent. Inasmuch as radical cations are not sensitive to oxygen, their preparation should be more facile compared with the

to vacum system

Figure 1. Apparatus for the preparation of radical anions (11). On connection of the entire vessel to the vacuum system, traces of water and oxygen on the wall are removed by heating and discharging with a tesla coil. When the apparatus is filled with purified nitrogen through A, the weighed sample of the hydrocarbon is put into B through C, a piece of sodium is put into D, and dimethoxyethane is distilled into E, where a small amount of an Na-K alloy is added. After the system is again evacuated the solvent is distilled from E into B, the bulb E issealed off at F, and the sodium is sublimed to form a mirror on the wall of the bulb G. After tubes at C and H are sealed off, the apparatus is pumped to high vacuum for 1 hr and then sealed off at J. Then the solution of the hydrocarbon is poured from B into G. After a time varying from several minutes to several hours, a color is observed, and the sample is ready for optical and esr measurements.

generation of radical anions. However, the difficulty generally encountered is that in addition to electron transfer, eq. (l), an electrophilic addition, eq. ( 2 ) , can occur:

D t A 2 D'tA-

(1)

K

D t A 2 D-A

(2)

The oxidizing agents are mostly Lewis acids such as BF3, AlC13, BBr3, or SbClS . For some systems, sulfuric acid can be used; SOs is probably an active component. The following examples demonstrate the reactions in equations (1) and (2):

PHYSICAL PROPERTIES AND REACTlVlTY OF RADICALS

331

aH @BBr,

+

\..-.'

BBr,

A study of reactions ( 1 ) and ( 2 ) gave a result (13) which is not very encouraging ', is obtained in high from the preparative point of view. A radical cation, D yield only from those conjugated systems, D, which have a low oxidation potential [high value of K1 in eq. (I)] and a weak basicity [low value of Kz in eq. ( 2 ) ] . This requirement, however, can hardly be fulfilled for actual systems. This can be demonstrated with benzenoid hydrocarbons, for which the basicity constant, K z , represented by the minimal value of atomic localization energy is found to be correlated (1 4) closely with the oxidation potential, Kl, represented by the energy of the highest occupied molecular orbital (Figure 2 ) . This finding implies that easier oxidation is inevitably connected with an undesirably stronger basicity; the effect of the latter makes physicochemical studies in a system of competitive reactions (1) and (2) difficult.

2.61

I

I

I

I

I

I

I

I'

I

I

7

2'4[ 2.3

I

I

2.0

1.9

7.8

[/

0.2

I 0.4

I

I

0.6

I

1

1x3 0.8 E (HOMO), 19

Figure 2. Minimum atomic localization energy in benzenoid hydrocarbons plotted against energy of the highest occupied molecular orbital (HOMO). Designation: a-naphthalene-likepositions (O), meso-anthracene-like positions (0).

Figure 3 . Controlled-potential electrolysis cell for generation of radical ions in the cavity of esr spectrometer [from (16) by permission of the authors and the American Chemical Society].

332

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

333

Hoijtink and co-workers (13) found that with some hydrocarbons, a concentration of radical cations can be enhanced by the uv irradiation of the reaction mixture, under which a fission of the addition complex to the radical cation occurs. Further progress in preventing reaction (2) could be achieved by sterically hindered oxidizing agents. A method of rotating cryostate (15) is a promising technique for study of unstable radicals. Electrochemical reductions and oxidations proceed in a more defined and controllable fashion because the potential can be maintained at the value suitable for a one-electron transfer and the course of the electrolysis can be followed polarographically and by measurement of the esr or electronic spectra. In some cases, conversion is low, which may be disadvantageous. Electrolytic generation of radical ions is a general method, and it has therefore become widely used in various applications. In Figures 3 and 4, we present electrochemical cells adapted for esr studies and for measurements of electronic spectra. Recently, electrochemical techniques have been developed that permit generation of unstable radicals at low temperatures (18-21). Droppinq Hg

electrode

Figure 4. Controlled-potential electrolysis cell adapted to measurements of electronic spectra of generated radicals (1 7). Dissolved oxygen is removed by pure dry nitrogen which is passed through an inserted polyethylene capillary. During the measurements, the capillary outlet is kept over the surface of the solution. Connection switching permits the carrying out of either the three electrode polarographic measurements (Hg dropping or Pt rotating electrode, S.C.E., and auxiliary electrode) or electrolysis (Hg pool or Pt working electrode, S.C.E., and auxiliary electrode).

Radiation methods, pulse radiolysis (22, 23), and y irradiation techniques (24) prove to be elegant and versatile methods not only for generation of unstable radicals, but also for the study of their physical properties and reactivity.

334

RUDOLF ZAHRADN~KAND PETR ~ A R S K Y

C. Quantum Chemical Methods The existing SCF procedures are of two types: in restricted methods, the MO’s, except for the highest (singly) occupied MO, are filled by two electrons with antiparallel spin, while in unrestricted methods, the variation procedure is performed with individual spin orbitals. In the latter, a total wave function is not an eigenvalue of the spin operator S2, which is disadvantageous in many applications because of a necessary annihilation of higher multiplets by the projection operator. Since in practical applications the unrestricted methods have not proved to be remarkably superior, we shall call our attention in this review mainly to the restricted methods. In the unrestricted treatment, the eigenvalue problem formulated by Pople and Nesbet (25) resembles closely that of closed-shell treatments:.On the other hand, the variation method in restricted open-shell treatments leads to two systems of SCF equations which have to be connected in one eigenvalue problem (26). This task is not a simple one; the solution was done in different ways by Longuet-Higgins and Pople (27), Lefebvre (28), Roothaan (29), McWeeny (30), Huzinaga (31,32), Birss and Fraga (33), and Dewar with co-workers (34). In this paper, the all-valence-electron semiempirical methods will be emphasized, even though the number of reported applications to radicals is still rather small. However, it can be anticipated to soon increase considerably. On the other hand, ab initio calculations are mentioned briefly because of the chemical orientation of this article. We give here only references to recent open-shell ab initio treatments, but no attempt has been made to make the coverage exhaustive. Millie and Berthier (35) have discussed all-electron wave functions of vinyl and methyl in the LCGO-MO approximation using Roothaan’s open-shell technique, Results for the excited states of the methyl radical were reported by McDiarmid (36) and by Barnard and Duncan (37). A series of papers has appeared in which the unrestricted Hartree-Fock computational scheme (25) was employed to interpret esr coupling constants; the actual applications concerned HzNO (38), vinyl (39), NH-, NH’ (40), NH2 (41), and NH: (42) radicals. The stability of the NF2 radical was examined by Noble and Kortzehorn (43). Hillier and Saunders (44) have developed a new SCF procedure which then applied to fluorosulfate radical: the transition energies obtained, however, reproduce the observed ones less satisfactorily than do the results of the unrestricted CNDO treatment (45). Peyerimhoff and Buenker (46) used the SCF functions of the allyl cation as the core functions in the treatment of the allyl radical. Lorquet and Cadet (47) calculated the transition energies of the N 2 0 * radical to discuss the observed photoelectron spectrum of N20. On the basis of ab initio calculations, Brundle and collaborators (48) have interpreted the photoelectron spectrum of NO2. Several attempts have been reported to interpret electronic spectra of radicals. Nitrogen dioxide has been studied most

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

335

intensely (49-51); DelBene also studied NH2 and NF2 radicals (51). Finally, calculations on large systems such as pyridine (52) and benzene (53) positive ions should be mentioned. 1. SCF Methods and ConfigurationInteraction The most frequently used SCF methods are those of Roothaan and of Longuet-Higgins and Pople. The former is more accurate but at the same time more complex than the latter. It has the significant advantage of being amenable to systems having more than one degenerate or nondegenerate open shell. On the other hand, the convergence of its procedure is slower, and in some cases of highly symmetric systems (e.g., linear radicals) regular oscillations in the SCF procedure even occur (the nth and (n - 2)th iterations are identical from the beginning) (54). Assuming the zero differential overlap approximation, the Hartree-Fock operator matrix elements are expressed (55) in the form Fp, = Hiv + 2Jc,pv - K c , ~ u+ 250, MU

-

KO,,, +
I- ( B D T ) ~ Bw

(3)

where

Core matrix elements, Hb, will be specified with individual methods. Indices k and m refer to closed and open shells, respectively; c and y have their usual meaning of expansion coefficients and repulsion integrals, respectively. Numerical values of constants f, a, and b depend on the electronic configuration under study: e.g., for a system having an unpaired electron in a nondegenerate

RUDOLF Z A H R A D N ~ KAND PETR CARSKY

3 36

level, f = .5, a = 1, b = 2 . Total electronic energy (not including core-core repulsions) can be expressed (29,56) as

E=

cc[(H;,+Fpu)D~,pu-Qpu(D~,,u

‘fDo,,u)I

(12)

Iru

where Qpu

= 6pu2a C D O , o a ~ p o- 0 ~ p u D 0 , p u

(13)

The first term in the eq. (1 2) can be simplified m-1

C

C z ~ p v ~ T , p v =

i= 1

gi+fCgm m

(14)

where 8, and I%, are orbital energies of closed and open shells, respectively. In the approach of Dewar and co-workers (34), termed the “half-electron method”, a physical model is considered in which an unpaired electron is replaced by two hypothetical “half-electrons” of opposite spin. For radicals containing one unpaired electron, the eigenvalue problem of this method is, in our opinion, identical with the method of Longuet-Higginsand Pople* (27): + 4PppYpp +

=

Fpp

c PuoYpu

(1 5 )

O(+P)

Fpu =HCpu - ‘1p puYpu

(lu#v)

(1 6 )

where (m-1) ppu=2

C

~ c i u + ~ p c u

(17)

i= I

The F matrix elements in eqs. (15) and (16) are formally the same as for closed-shell systems, the only difference being the definition of the density matrix in eq. (1 7), where the singly occupied orbital (m) has also to be taken into account. The total electronic energy (not including core-core repulsions) is given by

E=

cc f

Ppu(Fp, + H;u)

I r v

-

a cc

GpGu7pu

(18)

where, as in eq. (1 2), we can write

For reasons given later, we shall most frequently use in applications the method of Longuet-Higgins and Pople. Recently, the “half-electron method” was extended to the lowest-energy open-shell states of any given symmetry and multiplicity (57).

* Hereafter these two methods will not be distinguished.

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

337

In the unrestricted Hartree-Fock method, a single-determinant wave function is used with different molecular orbitals for (Y and spins, and the eigenvalue problem is solved with separate Fa and Fp matrices. With the zero differential overlap approximation, the F matrix elements (25) become

€$=

2

c&c$

i

The necessary equations for 0-spin MO's are identical with eqs. (20) through (22) with OL replaced everywhere by 0,and 0 by (Y. It should be stated that eqs. (3) through (21) are general in that they do not require a n-electron approximation and do not represent directly any specific computational method. In the n-electron approach with Pople's approximations, the F matrix elements become those below. Roothaan method:

where

0;u

= JX,,(l)HCXu(l)d~

(28)

I,, means the valence state ionization potential for the atomic orbital p , Zu stands for the core charge, and c& and x,, are coefficients and atomic orbitals in the LCAO expansion

RUDOLF ZAHRADN~KAND PETR ~ A R S K Y

338

The parameter set used in the calculations on closed-shell hydrocarbons appears to be appropriate also in treatments of open-shell systems (34,58-60). Moreover, it has been found to give reasonable results for radicals in ground as well as in excited states (61). In our laboratory, we use the following parameters for hydrocarbons: I, = 9.84 eV ycc = 10.53 eV

/3&

= -2.3 18 eV

Formerly, we used for Ic the value of 11.22 eV, which is commonly employed in closed-shell calculations, but a correct interpretation of ionization potentials requires (34) that IC be equated to the ionization potential of methyl radical, 9.84 eV. This change, however, does not affect the values of transition energies. Configuration interaction, which is necessary in treatments of excited states and desirable in calculations of spin densities, is more complex with open-shell systems. This is because more types of configurations are formed by one-electron promotions. These configurations (Figure 5 ) are designated as A, B, C,, C, ; G is the symbol for a ground state. Configurations C, and Cp have the same orbital part but differ in the spin functions.

----- - 8--8--4-8-4388ff88-s-e-

-88-

8888888888

G

A

B

Cd

cfi

Figure 5. Ground-state configuration and configurations corresponding formally to one-electron transitions for a system having one unpaired electron in its ground state.

Matrix elements for doublets constructed from the Longuet-Higgins and Pople SCF MO's are (10,27) C$A(i

+

m)lHl'$A(i

+

m)) - C k ' IHI'k) = b m -bj t f [(imlGlmi) t (mmlGlmm) - 2(imlGlim)]

(30)

+ f [(mkIGlkm) t (mmlGlmm) - 2(mklGlmk)]

(31)

t/z

O B ( m + Q)lH12&-&(i+. Q))= 2 [2(iQlGlkm)- (iQlClmk)t &~$(imlGlmm)] (43)

Ck,(i

-+ k)lHI2ka(h + Q)) = 2(hklGIQi)- (hklGliQ)

(kf Q) or (i#h)

(45)

RUDOLF Z A H R A D N ~ KAND PETR EARSKY

340

On the basis of Roothaan SCF theory, the following expressions hold (58, 62) for matrix elements between doublets:

?kp(i

+

k)lHl2$cc,(i + k)) - ('$G IHI'$G) = &k - Ei - (iklclik) t 2(imlGlmi) t 2(mklGlkm)

('$GIHIZ$cp(i QA(i

-+

<2$A(i

('$A(h

('j/,(h

+

+

k)) = 2 4 (imlGlmk)

m)lHIZ$A(h m)) = f(hmlGlmi) - (hmlclim) -+

+ m)lH12$B(m + k)) =

-+

m)lH('ka(i

m)lHiz$cp(i

+

k))=

(56) (h # i)

(imIGlmk) ~

42 [2(imlGlkh) -(imlGlhk) 2

t Ghi(mmlGlmk)]

(59)

4

(60)

?$,(m

-+

k)/HI2$B(m + Q)) = 3(mklGlQm)- (mklGlmQ) (k f Q)

?$,(m

-+

Q)lHl'$ca(i

(Z$B(m Q)lHl'$cc,(i -+

(61)

4 .

k)) = -- [2(iQIGlkm)t Gkp(imlGlmm) - (iQlGlmk)] (62) 2

-+

-+

k)) =

6[(iQlGlmk)- Gka(imlGlmm)]

(63)

2 ?k,(i

-+

k)lHl'ka(h

(57) ( 5 8)

k)) = 2 [tihifmmIGimk) - (imlGlhk)]

+

(52)

-+

Q ) ) = 2(hklGIQi)- (hklGliQ)tti,i(mklGI

t&Q(hmlGImi) ( k # Q )

Qm) or

(ifh)

(64)

PI-IYSICAL PROPERTIES AND REACTIVITY OF RADICALS

?k,(i +. k)lHI2&,(h

+

Q)) =

@ [6hi(kmlGlmQ)- 6k~(hmlGlmi)] 2

34 1

(65)

\

?$C,(i

+= k)lHIz$+,(h += 2)) =

2 [tihi(mklGIRm)t 6kp(hmlGlmi)] - (hklGliQ) (h+i)

or ( k f 11) (66)

Itlz$2), which are necessary for calculations of oscillator Expressions for strengths, are identical in both methods and can be found in the literature (10, 63). Also, the matrix elements for quartets are available (58). For testing the utility of individual approaches, we calculated (64) various characteristics (electron distributions, orbital energies, spin densities, coulomb repulsion integrals, transition energies) for a representative series of radicals by HMO and by both SCF methods. The SCF method of Longuet-Higgins and Pople (combined with configuration interaction) was found (64, 65) to be a versatile and very useful n-electron approach, and it can probably be employed in most cases instead of the more complex method of Roothaan. It is noteworthy that some reasonable characteristics are obtained even from HMO: however, differences such as in HMO and SCF electron densities are not negligible. From the point of view of the present state of computational possibilities, an extension of open-shell methods to u and u t n electronic systems is rather tempting. This extension is easy for the method of Longuet-Higgins and Pople: e.g., the CND0/2 method is amenable to radicals having one nondegenerate open shell if in the original terms for F matrix elements (66),

the density matrix elements are corrected (67) for the open shell (m):

In the Roothaan method, within the CNDO approximation the elements of the F matrix and of various matrices contributing to the F matrix are (68):

342

RUDOLF Z A H R A D N ~ KAND PETR

EARSKY

where ~c,p= p

Ck Ca c i a ~ p a= C ~ c , o o ~ p= aCB ~

cBBYAB ,

(72)

0

The total energy in the framework of both discussed methods is given by eqs. (1 2 ) and (18). The description of configuration interaction given for n-electron methods is also valid for all-valence-electron methods. Recently, two papers were published in which the “half-electron method” was combined with a modified CNDO method (69) and the MIND0/2 method was combined with the Roothaan method (70). Appropriate semiempirical parameters and applications of all-valence-electronmethods are most probably the same as those reviewed for closed-shell systems (71). 2 . Simple Methods

These methods can give us useful information on radicals in a manner similar to that for closed-shell systems, provided the exploitation is correct. Of course, in expressions for total energy, bond orders, etc., a singly occupied orbital must be taken into account. One should be aware of areas where the simple methods give qualitatively incorrect pictures. The HMO method, for example, cannot estimate negative spin densities or disproportionation equilibria. On the other hand, esr spectra of thousands of radicals and radical ions have been interpreted successfully with HMO. On the basis of HMO orbital energies and MO symmetry

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

343

properties, one can understand the nature of,electronic spectra of hydrocarbon radical ions (59) in a semiquantitative way. Several instructive HMO applications to radical reactivity are presented in the famous book of Streitwieser (72) and in the review of McClelland (73). Finally, let us recall the well-known procedure of Longuet-Higgins (74), which allows the determination of HMO expansion coefficients of nonbonding MO's in odd alternant hydrocarbons without solution of the respective secular equation. The extended Hiickel method has been used in a discussion of properties and reactivity of radicals and biradicals (75). We have found it possible to correlate the basicity constants, ~ K B H +of, radical anions with extended Huckel data (76). A good deal of information on small radicals can be obtained from Walsh diagrams (77). These correlation diagrams allow the estimation of molecular geometry from the mere knowledge of the number of valence electrons. The procedure and arguments are similar to those presented by Mulliken (78), who discussed the shapes of ABL molecules in ground and excited states and interpreted their electronic spectra.

11. PHYSICAL PROPERTIES

A. Heats of Atomization Heats of atomization belong to the most important characteristics of ground states. Unfortunately, the number of conjugated radicals for which experimental data are available is very limited. A heat of atomization is defined as the enthalpy of the reaction

GHS -+ rC + sH; AH;

(80)

For radical cations a quantity, AH:, can be defined, the meaning of which is close to the heat of atomization. It is obtained by subtraction of the first ionization potential, I, of a parent hydrocarbon from the heat of atomization, AH, , of that hydrocarbon: G H , = mC +nH; AHa

(81)

Comparing eqs. (81) and (82), we obtain ( & H z t e = m C t n H ; AH,-I

(83)

The heat of atomization for a conjugated hydrocarbon can be expressed as a

RUDOLF Z A H R A D N ~ KAND PETR ~ A R S K Y

344

superposition of the u bond energy (Ecc, ECH) and the welectron energy, E, (34):

AHa=-E,tNCIP+E,CC+NHECH,

(84)

where E, includes also the core-core repulsions, En =

2 P

4PpdFpv + Hiv) - 4

C C G$.~GIUYPU t C C~ p v P

U

V

P>

v

(85)

and I, is a carbon valence-state ionization potential, NC and NH are numbers of carbon and hydrogen atoms. Energies of (7 C-C and C-H bonds can be treated either as constant values (34, 61), or evaluated from semiempirical relationships in which their dependences on bond length are considered (79, 80). Recommended constant values are as follows: Bond SP' C-H sp3C-H sp2C-spz C

E (ev) 4.3808 4.28 16 3.4920

Bond sp2c-sp3c sp3c-sp3c

E (eV> 3.8417 3.5647

With hydrocarbon radicals, a difference between the calculated and measured heats of atomization (34,61) amounts to about .2-.3%(Table I). Data of.such an accuracy are utilizable even for calculations of chemical equilibria. A fair agreement was also obtained with a series of radical cations (61). TABLE I Heats of Atomization (-AHd of Conjugated Radicals

Radical

Calculateda, eV Ref. 61 Ref. 34

Ally1 Benzyl or-Phenethy1 Cyclohexenyl Cyclohcxadienyl

32.08 65.64 17.89 63.71 58.30

31.85 65.94 18.24 63.49 58.14

Observedb, eV

31.92 + .16 65.78 f .29 78.19 k .27 63.54 f .22 58.14 f .22

a ,-Electron approach, method of Longuet-Higgins and

Pople. See (34) and references therein.

Experimental data on aliphatic radicals are more abundant. Unfortunately, the standard CND0/2 method is not even appropriate to estimate heats of formation of closed-shell molecules (71). Among the CNDO modifications suggested, the most successful is that of Fischer and Kollmar (81), who have

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

345

obtained satisfactory results for several hydrocarbons. Recently, this procedure was successfully extended to radicals (69) by its combination with the half-electron method (i.e., with the method of Longuet-Higgins and Pople). Also, the results obtained with the MIND0 method are rather encouraging (Table 11). TABLE 11 Heats of Formation (AHf) o f Radicals

Radical CH; CH,CH; CH,CH, CH, . (CH,),CH, CH,CH,CH,CH, . CH,CH,CH. CH, (CH,),C. Ally1 Phenyl nenzyl CH: C6 H: a

Calculated AHf, kcal/mole

Observed AHA kcal/mole

Computational method

33.5 28.6 23.9 19.7 19.3 15.2 7.4 35.2 71.7 48.6 272.4 243.9

34.0 25.7 21.0 17.6 17.0 12.4 6.8 37.0 71.0, 80.0 45.0 282.6 233.3

a

a a a a a a b b b b b

MINDO/I method, data from (82). MINDO/II method, data from (83).

B. Molecular Geometry: Bond Lengths and Valence Angles In a theoretical estimation of a molecular geometry, the total energy is minimized with respect to all bond lengths and bond angles; i.e., minima on an n-dimensional energy hypersurface are sought. In actual applications, however, a number of variables are usually restricted: for two variables, an energy surface is obtained; with one variable, a potential curve results. The first case can be demonstrated with tetramethylene biradical 8, a postulated intermediate in pyrolytic fragmentation of cyclobutane to two ethylene molecules. The H

H'

8

RUDOLF ZAHRADN~KAND PETR ~ A R S K Y

346

extended Hiickel energy was minimized (84) with respect to a and 8; the former was varied in the range 90-130", the latter in the range 0-180". The minima were found at a = 116", 8 = 105" and a = 112", 8 = 0". The second case is illustrated in Figure 6, where the total energy dependences on the C-C bond distance in ethylene radical ions are presented.

- 449.52

I

I

I

I

I

I

E,eV -460.15

-449.54 -460.17 -419.56 -460.19 -449.58

a 1.36

1.38

I

I

1.40

I

I

1.42

I

r, W

1.44

Figure 6. Potential curves for ethylene cation radical (full line) and ethylene anion radical (dashed line) calculated (68) by the method of Longuet-Higgins and Pople within the standard CNDO/2 approximation. The scale on the left-hand side concerns the total energy of the cation radical; the scale on the right-hand side concerns the total energy of the anion radical.

Equilibrium valence angles calculated by unrestricted CNDO/2 (66) and INDO (85) methods for several AB2 and ABJ radicals are listed in Table 111. We recalculated (68) this series of radicals by the restricted CND0/2 method (Longuet-Higgins and Pople) and obtained results which are practically identical with those in Table 111. The MIND0 method also appears to give reasonable results (82, 83). For qualitative discussions, Walsh diagrams (see Sec. I.C.2.) have proved to be very useful, for example, in determining the structures of AB2, AB3, and HAAH molecules in ground and excited states. These correlation diagrams show how MO levels change on passing from one extreme molecular geometry to another.

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

or

B-A-B

341

B

I

linear

A-B bent

B

I

B /A\ B

:iA\B

or

planar

pyramidal

H-A-A-H

01

H\

A-A, H

trans

linear

The exploitation, which is, of course, the same as with closed-shell systems (86), is based on the two following plausible assumptions: 1. All molecules of a particular type have orbital energy level schemes that are qualitatively similar but differ in the number of valence electrons; for example, BH2 and NH2 belong to the same diagram. 2. Total energy of a system is considered simply as a sum of occupied orbital energies. TABLE I11 Calculated and Experimental Equilibrium Valence (B-A-B) Angles for AB; and AB, Radicalsa Radical NH, ('B,) NH, (* n - * A,) BO,

co:

NO2 NF2 CH, CF,

CNDO/2

INDO

Experiment

107.3 145.1 180.0 180.0 137.7 102.5 120.0 113.5

107.2 140.3 180.0 180.0 138.5 101.7 120.0 111.6

103.3 144 180 180 132 104.2 120.0 111.1

a Taken from (85).

Bond lengths in conjugated radicals can be estimated from a popular relationshp between the bond length and 71 bond order. Experimentally, the molecular geometry has been determined by X-ray analysis for several larger radicals. These data indicate, in agreement with the theory, that bond alternation characteristic in many reduced and oxidized closed-shell forms is diminished in radical ions. Precise crystallographic data are available for 4,4'-bis(dimethy1amino)diphenylamine radical cation (87, 88), N,N'-diphenyl-p-phenylenediamine radical cation (89), and Wurster's blue (90).

RUDOLF Z A H R A D N ~ KAND PETR CARSKY

348

With a series of small radicals, the analysis of rotation lines has resulted in determination of rotational constants. Some of those which are employed in calculations of molecular geometry (91) are summarized in Table IV. TABLE IV Rotational Constants (A, B, C), Bond Lengths (I, A) and Bond Angles (a)for Small Radicals According to Herzberga

Molecule

Point group

State

A

n

-

6.1 7.25 3.57 4.4 8.8 12.94 5.606 8.087

41.64 -

13.6 23.73 20.340 9.120

HCO

A'A" g2A'

C-v Czv

22.31

1.338 1.494

C

r

-

1.17 1.18 1.53 1.59 1.OO 1.024 1.403 1.428 H-X 1.04 (1.08)

6.01 -

3.3 -

8.17 4.311 4.225

1.401

01

180 131 180 119 (144) 103.4 123.1 91.5

X-Y 1.187 1.20

180 119.5

a (91).

C. Spectroscopies in the Framework of One-Electronic Level

T h ~ stopic covers electron spin resonance (esr) and rotation-vibration spectroscopy. Since esr has been reviewed on many occasions, both from the theoretical and experimental standpoints, we present here only a brief description of computational possibilities on spin densities. A comprehensive study of 7r-electron methods was published recently by Tiho (92) who, for a representative set of conjugated radicals, analyzed results obtained by several restricted and unrestricted methods. From that comparison, the method of Longuet-Higgins and Pople combined with configuration interaction appears to be one of the most successful methods. Since the HMO method gave surprisingly good results for many 7r radicals, the extended Huckel method could be anticipated to provide a straightforward extension to u radicals. A difficulty involved in that extension will be shown with cyclohexadienyl, 9. An odd unpaired electron occupies a n-molecular orbital in 9 for which the extended Huckel calculation gives the following form (93): ~ p =.116x(C8,

2pZ)-.570(x(C9, 2pJ+x(C13, 2 ~ 2 ) ) - . 0 2 9 ( ~ ( C ' ~2pz) ,

+X(C12, 2pz))+.605 x(C", 2pJ+.196(x(H6, 1s)-x(H7, IS)}

(86)

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS 6

349

7

H H

._.H3

9

It can be noticed there are two types of hydrogen atoms: atoms 1-5 lying in the molecular plane and atoms 6 and 7 lying out of the plane. Thus, the hyperfine splitting constants (aH) cannot be interpreted by means of one relationship, but the expressions aH = K u d l (87) aH = Kn'&

(88)

must be employed, from which the former applies generally to u radicals (hydrogens 6 and 7 in 9) and the latter to r radicals (hydrogens 1-5 in 9). In eqs. (87) and (88), cp means the singly occupied MO, cpk and cp; are spin densities on hydrogen and carbon bearing a hydrogen atom*, Ku and K, are empirical constants for the transformation of spin densities to hyperfine splitting constants. As a matter of fact, eq. (88) is the McConnell relationship adopted in r-electron MO treatments. In spite of the crude approximations involved in the extended Hiickel approach, the results are fairly good (93-96). The results for 9 and for vinyl, 10, are presented in Table V. With some other systems, however, 2

1

3

10

(e.g., phenyl, 1-naphthyl, and 2-naphthyl) the agreement with experimental data is less satisfactory (97). It should be mentioned that the extended Hiickel method, similarly to the HMO method, cannot interpret negative spin densities. In order to obtain nonzero spin densities even on hydrogen atoms in r radicals, one has to take the one-center exchange repulsion integrals into account in the eigenvalue problem. In other words, a less rough approximation than the complete neglect of differential overlap (CNDO) is required. This implies that in the CNDO/2 approach also, u and r radicals have to be treated separately (98).

* Extended Huckel calculations are performed with a nonorthogonalized A 0 basis set: therefore, the spin densities are to be evaluated by gross atomic populations and not simply by squares of expansion coefficients.

350

RUDOLF Z A H R A D N ~ KAND PETR CARSKY TABLE V esr Hyperfine Splitting Constantsa (aH) Positionb

C9(H') C'"(H') C"(H3) H6

H' H' H3

Experiment Cy clohexadienyl 8.99 2.65 13.04 47.41 Vinyl 13.39 65.0 37.0

Extended Hiickel method

9.12' .02' 10.34' 43.23d 8.8d

69.7d 38Sd

a I;rom (93) and (94); all values are expressed in

gauss. Numbering of positions is same as in formulas 9 and 10. Eq. (88) used, Kn = 1066. Eq. (87) used, KG = 1887.

Yonezawa and collaborators (99) have reported unrestricted open-shell SCF calculations where the one-center exchange integrals were taken into account; their treatment concerned allyl, vinyl, and nitrogen dioxide radicals. The one-center exchange integrals also are involved in the INDO method (85). Here, the following relationship for hyperfine splitting constants holds:

where the symbol R stands for the kind of nucleus (e.g., 'H, or 19F), psRSR is the spin density in a valence s atomic orbital on the nucleus R, and K ~ i an s empirical constant. Pople and collaborators (100) tested the unrestricted INDO method on an extensive set of 57 radicals of various structural types and interpreted the hyperfine splitting constants of 'H, 13C, 14N, "0, and 19F nuclei. The overall results are satisfactory: 92% of the proton isotropic hyperfine splitting constants are calculated to within 3 gauss. In the calculations, the interatomic bond distances were chosen as constants depending entirely on the nature of two atoms involved: for example, in 9 , all CC bonds were given the length 1.40 A . By assuming more realistic molecular geometries, a better agreement would probably be achieved.* Another interesting result of that INDO study is a linear relation found between the hydrogen 1s orbital unpaired electron populations and the adjacent carbon 2p, orbital unpaired electron

* Pedersen (101) obtained very good results by the same procedure for HCO, HCN-, and FCO radicals optimizing the molecular geometries.

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

35 1

populations for a number of positions in a variety of 71 radicals. This proportionality provides direct evidence for the simple McConnell relation. Since the rotation spectra are most interesting for the determination of molecular geometry, they were mentioned in Section 1I.B. Vibration spectra were recorded for a series of small radicals (91). Theoretically, these values can be obtained from the Wilson matrix analysis (102). This procedure can be used for vibrational analysis in a ground state as well as in excited states. From the high-resolution electronic spectra, one can get experimental information on the vibrational structure of excited states. Remarkable progress in this field has been achieved in recent years by the introduction of photoelectron spectroscopy (PES; see the following section, 1I.D.). Individual bands in these spectra exhibit vibrational structure, the analysis of which can even give several line progressions for high resolution in favorable cases. In Figure 7 the data of Turner (103) for formaldehyde are presented as an example. Here the vibrational structure ' cation. The vibration frequencies determined are listed concerns the CH20 together with adiabatic ionization potentials in Table VI. The system possesses six normal vibration modes (3 x 4 - 6 ) : three of them are totally symmetric and are allowed in CH2O as well as in the ground state of CH20'. The remaining three modes are allowed in monodeuteroformaldehyde, which has a lower symmetry.

Figure 7. The photoelectron spectrum of formaldehyde with the data on adiabatic ionization potentials. The fourth potential can be determined only at higher resolutions. [From (103) by permission of D. W. Turner and the publishing house].

D. Ionization Potentials and Electron Affimities Ionization potentials and electron affinities are among the most theoretically useful physical quantities. While the measurement of electron affinities is still

RUDOLF ZAHRADNiK AND PETR EARSKY

352

TABLE VI Ionization Potentials and Vibration Frequencies of Formaldehyde and its Radical Cation [after Turner (103)]

State Ground, ' A , Bl

ZB, aB2

lA, a

Vibration frequenciesb, cm"

Band in the photoelectron spectrum

I, eVa

1. 2. 3. 4.

10.88 14.09 15.85 16.25

-

1

2780 2560 (1400?) 1400?

2

3

1744 1590 1210 1270

1503 1210

-

-

1270? -

Adiabatic ionization potential. See Figure 7.

technically a difficult task, remarkable progress has been achieved in measurements of ionization potentials. Photoelectron spectroscopy (PES) and Penning ionization electron spectroscopy (PIES) permit the measurement of higher ionization potentials (frequently up to 20eV) with high accuracy. In Figure 8, the spectra obtained by both methods are presented for the NO radical. Until now, the number of spectral data on radicals has been rather limited. The ionization being accompanied by a vibrational excitation, the fine structure of bands can be exploited for determination of vibrational levels of an ionized system in the ground and excited states. Of course, the first (0-0) and the strongest vibrational bands are the most important because they determine adiabatic and vertical ionization potentials of radicals. Even the photoelectron spectroscopy of closed-shell molecules is valuable for the physical chemistry of radicals because a difference between the nth and the first adiabatic ionization potentials determines the excitation energy in a radical cation for a transition from the ground doublet state to the (n - 1) excited doublet state. In the HMO or extended Huckel approach, the individual ionization potentials should be set equal to orbital energies. The inadequacy of the HMO treatment is apparent with odd alternant hydrocarbons (e.g., allyl, benzyl), where a constant value is obtained, in disagreement with the experiment. Streitwieser and Nair (105) showed, however, that reasonable results can be obtained with the w technique. Assuming the same molecular geometry and the same MO's for both the parent and ionized systems, the first ionization potential can be expressed in the SCF approach (Longuet-Higgins and Pople or Roothaan) (106) as

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

353

9.24

L i i15.75 0.1 183 I663

’i’ I , I l 1111, , , A l I

20

I8

16

14

12

10

8 eV

Figure 8. Photoelectron spectrum (PES) and Penning ionization electron spectrum (PIES) of nitric oxide radical. Average vibrational energy spacing of the first band amounts t o 285 and 284 cm-’ ,respectively (104).

-I = E(R(”-’)+)

-

E(R”+) = b, - iJ,,

where m is the index for the singly occupied MO in a radical, b, energy of that level and Jmm is the Coulomb repulsion integral,

(90) is the orbital

Eq. (90) can be called an extension of Koopmans’ theorem to radicals. Recently, Richards (107) discussed the approximate nature of Koopmans’ theorem in treatments of closed-shell systems, and most probably his arguments apply here also. For an electron removal from lower MO’.s, the situation is more complicated, because either an a-spin electron or a b-spin electron can be removed. Hence, the ionized system formed can be in a singlet or a triplet state.

354

RUDOLF Z A H R A D N ~ KAND PETR EARSKY

It is notable that the known singlet-singlet and singlet-triplet transition energies (i.e., electronic spectrum) from the ground state of the ionized system permit the determination of relative values of ionization potentials of the radical from its first ionization potential. In the framework of the method of Longuet-Higgins and Pople, the following expressions for higher ionization potentials can be derived in a manner similar to eq. (90):

where e2 r pm(l)qi(2)d71 ~

Kim = SSqi(l)qm(2)

12

T Z

(94)

If we assume a singlet ionized system, relation (92) holds, while for a triplet system, eq. (93) is valid. It is noteworthy that the difference in the ionization potentials 1: and 1: of the radical is equal, in the SCF approach, t o the difference in transition energies, and in the ionized system:

If - 1 : =

-

3A&i-.m = 2Kh

(95)

Finally, the expression for the electron affinity for the uptake of one electron into the singly occupied orbital (m) should be mentioned (106): -Am = G,,, +4Jmm

(96)

Until now, applications of semiempirical all-valence-electron methods have been rare, although the experimental data for a series of alkyl radicals are available (1 08, 109). In Figure 9, we present the theoretical values of ionization potentials calculated (68) for formyl radical by the CNDO version of Del Bene and Jaffi (1 lo), which is superior to the standard CND0/2 method in estimation of ionization potentials of closed-shell systems (1 11). The first ionization potential is seen, in Figure 9, to agree fairly well with the experimental value. Similarly, good results were also obtained (1 13) with some other radicals (Table VII). For conjugated alternant hydrocarbon radicals, eq. (90) can be simplified (106) to

-I=F,,,,-+J,,

(97)

where the usual formalism of Pople is used:

F,,,, = Up,, +h-y,,,, = constant

(98)

With the parameter set given (Sec. I.C.l.) we obtain F,,= 4.57 eV. Thus, eq. (97) provides an interesting prediction: the larger the skeleton, the lower the value of Jmm ; for an infinite skeleton, J m m = O and ,-I = F, : i.e., the ionization

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

, , ,

i

355

A:=-1.69

/

+I J 2 66 ~

-I,= S

__---

T

1, = u.27

++
1

-97.87

1,T --I5-%. 5-

..'._ .

-15.14

-4-+.3z;-<

--

....

.-

96

;1 = 17.34 I, = 47.77

----.---;--

-- - -- -

10.01

--- .-

1: = 19.46

Figure 9. Determination of the first electron affinity, and the first and higher ionization potentials of formyl radical from the SCF orbital energies and electronic repulsion integrals, J,, and K,, (cf. eqs. (go), (92), and (93)). The experimental value (112), 9.88 eV, for the first ionization potential corresponds to the theoretical value 1:. All entries are given in eV. With A and I a lower index stands for MO: the upper one indicates the state multiplicity after ionization.

TABLE VII Calculated and Experimental First Ionization Potentials of Small Radicals (1 13) Radical

BH,

NH,

HCO

NO,

NF,

Calculateda Observedb

10.16 9.8

11.96 11.4

10.01 9.88

11.11 11.23'

12.36 11.8

a CND0/2 with DelBene-Jaffb parametrization [for geometry, see (91)] ; open-shell method of Longuet-Higgins and Pople; eq. (90). Mass spectrometric data (91). Vertical potential; photoelectron spectrum (48).

356

RUDOLF Z A H R A D N ~ KAND PETR ~ A R S K Y

potential of any odd alternant hydrocarbon should lie in the range of 4.57-9.84 eV. The hitherto reported results of semiempirical n-electron methods are summarized in Table VIIl. TABLE VIll Ionization Potentials of Conjugated Hydrocarbon Radicals

Radical Ally1 Pen tadieny 1 Bcnzyl Benzhydryl e-Naphthylmethyl p-Naphthylmethyl Vinylcyclopentadienyl Indenyl Fluorenyl

Observed, eV

Hush and Poplea

8.16e 7.73f 7.73e 7.32g 7.35g 7.56g 8.44h 8.35h 7.0Ih

6.23

Calculated, eV Streitwieser Dewar and and Nairb ~011.~

-

-

8.32 7.89 7.48 6.9 1 7.03 7.14

-

-

-

-

-

-

-

._

7.78 7.26 7.35

~

-

8.22 1.74 7.76 -

&sky and Zahradnkd

8.16 7.46 7.64 1.02

7.17 7.45 8.37 7.93 7.43

a Calculated by eq. (97), (106). w technique, (105). Calculated as differencesbetween total SCF energies of the neutral hydrocarbon and the corresponding positive ion; radicals were calculated by the half-electron method, (34). Method of Longuet-Higgins and Pople; eq. (90) was employed, (61).

(1 14). (105). (1 15). h(116).

E. Electronic Spectra Optical spectra of radicals are interesting from the theoretical point of view because the first band or even several bands even with small systems are frequently located in the visible region. With many systems, the process of electron-shell opening is connected with a considerable red shift of the first (longest wavelength) band, this shift being sometimes of several eV. Transition energies are diagramed schematically in Figure 10 for oneelectron functions (MO’s) and many-electron Cl functions. Four types of singly-excited configurations mentioned in Section I.C. 1. correspond to electron promotions indicated in Figure 10a; configurations C, and Cp differ by spin functions. With configurations possessing three open shells, the quartet state lies below the doublet C, and Cp configurations, as required by Hund’s rule. The somewhat striking position of the first quartet state above the several lowest

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

351

excited doublet states is caused by the fact that A- and B-type excitations can lead to doublet states only. This energy-level scheme appears to be general and provides an explanation for why phosphorescence was observed only with one radical, decacyclene mononegative ion (1 17), while fluorescence is common. Nonradiative transitions from higher excited doublet states to D, are probably very rapid and therefore the hope for the intersystem crossing population of Q1 is rather small. A similarly small success can be anticipated in direct D-Q absorption measurements: even if we succeeded in enhancing the intensity of these spin-forbidden transitions, it would always mean seeking a very weak band overlapped by several rather strong bands. A promising method for attacking this problem appears to be spectroscopy by thermal electrons (instead of photons), where the D-Q transitions are not spin forbidden.

kp . . . . . . . :._ .. ...........

.....;.. .:.;

0

.........

-

.... . . . . . . . . 'u ....... ... ....... ..:. 50

rn ;:A'':;:.:::

3

..\.;,::.:.: L ............ ......... .. ..................... ......... ; .......... . . . . ..... $

$2

4

PtJ2 I*€,-

U

-c-b

.

-Al;

-K

-t--t Y,

(2wJ2Eo-

Figure 10. Electron excitations in radicals: (a) Collective representation of oneelectron transitions of the A, B, and C types; q denotes MO: (b) LCI energy-level scheme (Jablonski diagram) for doublet and quartet states indicating why with radicals fluorescence (- . . -) but not phosphorescence is observed. Spin-forbidden transitions are represented by dashed lines. ~

Spectra of small radicals were studied intensively in a qualitative and semiquantitative way [Mulliken, Walsh (77)] but a very small number of quantitative studies has been published. It is, however, beyond doubt that this region will become very topical. Within the CNDO approximation, attempts have been made to interpret the electronic spectrum of HZNO radical (67) (method of Longuet-Higgins and Pople), SO3 F radical (45) (unrestricted method), and HCO radical (68) [method of Longuet-Higgins and Pople incorporated into the CNDO version of Del Bene and Jaff6 (1 lo)]. From the two observed bands for the HCO radical, the first, located at 1 1,600-21,700 cm-', was assigned to the transition from the ground doublet state, while with the second, a t

35 8

RUDOLF Z A H R A D N ~ KAND PETR CARSKY

24,400-38,500 cm-’, a possible transition from the excited state could not be excluded (91). The calculated transition energies, 15,100, 36,000, and 36,700 cm-’, with the oscillator strengths .004, .002, and .033, respectively, support the assignment of both bands to the HCO Do +. Dx absorption. The first two calculated transitions are little affected by the configuration interaction and can be denoted as n -+ n* and 71 +. n transitions. The third calculated transition has the character of a u + n electron promotion. The same method, i.e., the CNDO version of Del Bene and Jaffi, also gave fairly good results for both butadiene radical ions (1 18). With ‘II radicals, the theoretical studies are more numerous. It appears that the SCF method of Longuet-Higgins and Pople in the n-electron approximation combined with the configuration interaction (CI) treatment permits satisfactory interpretation of several longest-wavelength bands. The expressions for the SCF transition energies are somewhat more complex in comparison with those for a system having a singlet ground state: they are given by eqs. (30) through (33) and (49) through ( 5 2 ) . For a CI basis comparable to a “usual” basis treatment of closed shells, a considerably higher number of configurations need to be taken into account with radicals. By the “usual” basis with a closed-shell system, we mean generally about 16 singly excited configurations arising from electron promotions between the four highest doubly occupied orbitals and the four lowest vacant orbitals. Considering analogous excitations for a doublet ground state and, in addition, all electron transitions which result from a singly occupied MO, we get altogether 41 configurations: 4 of the A type, 4 of the B type, 16 of the C, type, and 16 of the Cp type; the 41st configuration is the ground-state configuration, which, in contrast to the singlet ground state, interacts with some singly excited configurations (compare Sec. I.C.1.). Of course, the most significant configuration mixing is that of the first order, which takes place, for example, with odd alternant hydrocarbons (such as ally1 or benzyl), mixing the A- and B-type configurations. Almost the first-order CI is met with various large radical ions where the natural N +. V gap approaches the unnatural N +. V gap (vide infra). Useful information can even be obtained from an entirely qualitative point of view. Considering that except for very large systems the gap between the highest occupied MO and the lowest unoccupied MO for closed-shell systems (N -+ V1 gap, “natural” gap) is much larger than gaps between these orbitals and respective next occupied and unoccupied orbitals (“unnatural” N + V gaps), a significant shift accompanying the formation of both radical ions can be understood (Figure 11). Empirically it was found that with uncolored systems, this shift is greater than with colored systems. Systems of another type where a considerable shift can be expected are those which can be considered as being built up from two conjugated subsystems joined by a formally single bond; a

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

359

great effect should be achieved by joining the subsystems in positions permitting only a weak conjugation (59). A useful result is the correlation of the lowest CI excitation energies with the HMO energies of the corresponding transitions (59).

t

antibonding MO’s

‘1/ -

--- - GAP

-

f-

REGIONS

OF UNNATURAL N*V

+

bonding MO’s Figure 1 1. Typical scheme of MO energy levels of a closed-shell hydrocarbon.

Ally1 (27, 60, 119-125) and benzyl (26, 27, 60, 121, 125-133) radicals have been studied intensively. Other theoretical studies have concerned pentadienyl(60, 124), triphenylmethyl-type radicals (27), odd polyenes and odd a,w-diphenylpolyenes (60), radicals of the benzyl and phenalenyl types (60), cyclohexadienyl and a-hydronaphthyl (1 34), radical ions of nonalternant hydrocarbons (1 1, 135), radical anions derived from nitroso- and nitrobenzene, benzonitrile, and four polycyanobenzenes (1 0), anilino and phenoxyl radicals (1 30), tetramethyl-p-phenylenediamine radical cation (56), tetracyanoquinodimethane radical anion (62), perfluoro-2,1,3-benzoselenadiazoleradical anion (1 36), 0-protonated neutral aromatic ketyl radicals (137), benzene cation (138), benzene anion (1 39-141), paracyclophane radical anion (141), sulfur-containing conjugated radicals (1 42), nitrogen-containing violenes (143), and p-semiquinones (17, 144, 145). Some representative results are presented in Figure 12. Recently, a nonempirical n-electron SCF approach was reported and applied to interpretations of spectra of various conjugated hydrocarbon radicals (147). The greatest attention, however, has been paid to radical ions derived from even alternant hydrocarbons (10, 58-60, 63, 125, 135, 148-153). Here, numerous experimental material suitable for systematic testing of the MO methods has been accumulated. In particular, the following sources of experimental data should be mentioned: Hamill and collaborators (24) prepared

360

LogE1

...

09 f

0 &.j..:

....

-v

...

-1

I

L 5

1

I

-2 -3 log f

Log E 4

0 -1

3

-2 7

-50

40

30

20 F x 10:cm1

30

20

10

9 x10:cm1

Figure 12. Electronic spectra and the results of open-shell PPP-like semiempirical calculations for radical ions. The vertical lines represent the allowed transitions, the wavy lines with arrows the forbidden ones. The right side scales denote the calculated spectral intensities, where f stands for the oscillator strength. Top left: the absorption curve (146) redrawn to the log E vs. U (cm-’ ) form; calculations are taken from (59). Top right: taken from (11). Bottom left: taken from (143). Bottom right: taken from (136), the absorption curve redrawn to the log E vs. ii (cm-’) form.

radical ions from parent hydrocarbons by the y-irradiation in glasses of tetrachloromethane and sec-butyl chloride at -1 96”, Hoijtink and collaborators prepared the radical cations (1 3;154) by treating the parent hydrocarbons with sulfuric acid, trifluoroacetic acid, boron trifluoride, antimony pentachloride or by uv-irradiation of glassy boric acid solutions, and the radical anions (6, 7, 146, 148, 155) by alkali metal reduction. The close resemblance of the absorption curves of pairs of corresponding radical anions and radical cations of alternant hydrocarbons afforded strong evidence for “pairing properties” of MO’s predicted by the theory (156). In Figure 13, we ,present the orbital level diagrams for biphenyl radical ions, indicating the correspondence of MOs for which pairing properties hold. It can be noticed that the SCF excitation energies are identical for both ions. The same picture is obtained even in the configuration interaction treatment; thus, the open-shell PPP-like calculations give identical results for alternant radical cations and anions. As an example, we

PHYSICAL PROPERTlES AND REACTIVITY OF RADICALS

-1.625

- -2.402 - -4.194 - 4.880

Ill 3

2

-4.887

1

-6.040

-

-5.8?0 3.022

~~

-14.65?1

~~

-7.029 -2.716

-9.508 SHC -10.285 y'

A

- 44.226

* -l4.2651 -14.898

\-

11 2 3

-16.73 -17.970

C

Figure 13. Orbital energy-level scheme for the biphenyl anion radical (A) and biphenyl cation radical (C) based on the SCF calculations (59) by the Pople and Longuet-Higgins' method. Pairing of MO's is indicated. Thick lines with arrows represent the five lowest transition energies. All entries are given in eV.

selected results for tetracene ions (Figure 14). On the other hand, the electronic spectra of negative and positive ions of nonalternant hydrocarbons should differ considerably. The first absorption maximum of the acenaphthylene radical anion is seen in Figure 12 to be located at about 12,500 cm-', while for the first transition energy in the radical cation, the theory predicts (68) the value of 5,900 cm-'.

RUDOLF ZAHRADNiK AND PETR CARSKY

362

&lo

-i

I

I

I

I

I

I

I

V

40 30 20

10 4x10: V

40 30 20

ia 0

Figure 14. Absorption curves of the tetracene radical ions (157) and results of the semiempirical open-shell PPP-like calculations (59). The latter are indicated by vertical lines (allowed transitions) and by wavy lines with arrows (forbidden transitions); f stands for theoretical oscillator strength.

111. CHEMICAL REACTIVITY

The chemical reactivity of radicals is governed of course by the same chemical principles as the reactivity of systems having closed-shell ground states. Both equilibrium and rate processes are important here. The paucity of quantitative data on equilibrium and rate constants of radical reactions, suitable from the viewpoint of the present state of the theory, prevents a more rapid development in the MO applications: this difficulty, however, is not specific for open-shell systems . The present state of the theory of equilibrium processes is satisfactory. This holds, of course, only for gas-phase reactions between components of ideal or nearly ideal behavior. For actual equilibrium reactions of interest in solutions, the situation becomes more complex. Here a difficulty emerges because of a rather disappointing state of the theory of solvation phenomena. In reactions of

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

363

neutral radicals with neutral species in solvents of low polarity, the solvation effects often can be disregarded, but with radical ions, the solvation and association with counter ions play an important role. For an equilibrium reaction aA t b B + . . .tmM +nN t . . .

(99)

the equilibrium constant can be expressed as

where G stands for total partition function G = ftf,f,fvfefn

composed from the translation, rotation, restricted rotation, vibration, electronic, and nuclear partition functions. For small molecules in gas phase, all of these contributions can be calculated easily except the vibration partition function, the evaluation of which requires a knowledge of wavenumbers of normal vibrational modes; but approximate values can be obtained by means of the Wilson matrix analysis. The evaluation of the preexponential term in eq. (100) for gas-phase reactions is straightforward. The absolute zero enthalpy, Eo, can be obtained either from semiempirical calculations on products and reactants or by means of ab initio calculations with a subsequent estimation of the correlation energy. In compromising treatments, the experimentally estimated enthalpies can be employed. In the following, the MO applications will be demonstrated with two selected equilibrium reactions ,most important in radical chemistry: disproportionation and dimerization. The examples presented will concern MO approaches of different levels of sophistication: ab initio calculations with the evaluation of partition functions, semiempirical treatments, and simple procedures employing the HMO method or perturbation theory. The most advanced treatment leading to the absolute determination of equilibrium constants will be demonstrated with the two following simple reactions of methyl radical:

RUDOLF Z A H R A D N ~ KAND PETR CARSKY

364

The following molecular geometries (35,91) are assumed in the calculations: H H,s\s

12y4q

H

methyl radical and cation: planar

____

--c..........~

H'1.Q

H.)

methyl anion: pyramidal

H-C

,,,g

H'':

c-.--..H

\H

ethane: staggered

Table IX presents both the theoretical ab initio energies of the components of reaction (102) and the experimental values which allow evaluation of the error introduced by neglecting the correlation energy. TABLE 1X Energies of Methyl Cation, Radical, and Anion" CH

CH

-39.259 -39.486

Et hb Eexp

-39.584 -39.847

CH; -39.525 -39.898

From (351, all values are in eV. The Hartree-Fock limit with a relativistic correction. a

For the energy change accompanying the disproportionation, we obtain

A&

= 2E(CH;)-E(CH:)-E(CH:)

= -.384

a.u. G -10.37 eV G -239 kcal/mole

This result is an interesting one because on theoretical grounds the energy change of the disproportionation process can be set equal to the coulomb repulsion integral Jmm (vide infra), which, in the case of methyl radical, equals the one-center electronic repulsion integral, ,y,. In semiempirical methods, the value adopted for T,,, amounts to about 10 eV; a fairly good agreement of both numerical values is apparent. In the Wilson matrix analysis, the normal vibrational modes in methyl radical were assumed to be the same as those in both methyl ions. This assumption is rather crude: however, it is believed to influence the results very little. The following values for the normal vibrational modes were obtained (in cm-'): 3100;3100;2915; 1620; 1620; 1030. Translational functions in eq. (100) cancel out; because of the approximation adopted, the vibrational functions also cancel. The logarithm of the ratio of rotation functions possesses a constant value of -.246. The contribution of the exponential term is considerably higher and therefore determines the value of the disproportionation constant. Theoretical values of log K listed in Table X

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

365

represent a temperature dependence of reaction (102). As can be noticed, the equilibrium is shifted entirely in favor of the methyl radical, in agreement with the chemical anticipation. In general, appreciable concentrations of lower and higher oxidation levels can be formed in equilibrium with the radical only in solutions and only if the solvation and entropy-change effects are more significant than the repulsion term (vide infra). TABLE X Data for the ReactionCH;+CH:=+2

100 500 1000 1500 2000 2500 3000

CH;

523 105 52.6 35.2 26.5 21.3 17.4

For the enthalpy of dimerization, we used the experimental value (1 58) of -3.658 eV. One of the normal vibrational modes (corresponding to the mutual turning of methyl groups around the C-C bond in ethane with 0 = 275 cm-') was replaced by one restricted rotational degree of freedom. For the remaining 17 vibrational degrees of freedom, we obtained the following values (in cm-', degeneracies are given in parentheses): 2995 (2x); 2955 (2x); 2915; 2915; 1472 (2x); 1460 (2); 1400,1379; 1190 (2x); 993; 822 (2x). In contrast to disproportionation, in the dimerization equilibrium at lower temperatures the reaction product is favored. The contributions coming from partition functions and from the exponential term are presented together with the temperatures and logarithms of equilibrium constants of the reaction (1 03) in Table XI. TABLE XI Data for the 2 CH; + C,H, Reaction: Temperature, Partition Function Contributions, Exponential Term, Logarithm of the Equilibrium Constant T("K) 100 500

1000 1500

2000 2500 3000

Log (t) --.808 -1.857 -2.308 -2.572 -2.760 -2.905 --3.024

Log (r) -.275 - .579

-.I13 -.814

-.m

-.961 -1.027

Log (v)

Log (E)

Log K

.ooo

184.27 36.85 18.43 12.28 9.21 7.31 6.14

118.7 29.3 10.45 4.23 1.16 -- .64 -1.82

.120 .563 1.022 1.424 1.113 2.019

RUDOLF Z A H R A D N ~ KAND PETR ~ A R S K Y

366

Let us pass now to studies on a semiempirical level. For dimerization of neutral radicals in a gas phase or in a solution 2R'*D we can write

Furthermore,

-RT log K = AGO = AHo - TASO

(106)

Assuming a linear relation between AS" and AH" within a reaction series, the relative values of K can be estimated by means of the following expression -RT log K + const. = AHo = W(D) - 2 W(R')

(107)

For conjugated radicals, a contribution to AH" coming from u electrons can be treated as constant within the reaction series. Under this approximation, it is sufficient to consider only the 7i-electron energies. In general, the SCF values should be preferred, but it appears that a reasonable picture can be obtained in many cases even with HMO data. With radicals of the benzyl type, 11 through 18, the dimerization equilibrium depends on the relative magnitudes of the energy gain arising from the C-C bond formation and of the n-electron energy loss which results from a reduction of the conjugated system.

12

11

14

13

CH 1

an"' 020 mC 15

17

16

18

For example, the n-electron energy change in the dimerization of benzyl is taken as a twofold difference in the n-electron energies of benzene and benzyl. With the SCF data, a double value of the valence state ionization potential of carbon [I in eq. (25)] has to be added to this difference. The entries of Table XI1 show that in all equilibria considered, a dimer is favored.

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

367

TABLE XI1 Estimations of Dimerization Enthalpies for Radicals of the Benzyl Type 11 through 1 8a (1 13)

HMO datab Radical 1I d

12 13 14 15 16 17 18 a

_ _ _ ~

SCF data'

Calculated AH, kcal/mole

W(D)

2W(R')

W(D)

2W(R')

HMO

SCF

16.000 27.366 27.366 38.627 38.627 38.627 49.862 49.862

17.442 28.990 28.854 40.324 40.166 40.530 51.438 51.876

- 155.164 -259.912 -259.912 -364.328 -364.328 -364.328

-178.858 -283.720 -283.562 -388.184 -387.964 -388.658

-59.4 -56.5 -58.7 -55.4 -57.9 -52.1 -57.3 -50.4

-53.3 -50.6 -54.3 -49.5 -54.6 -38.6

The dimerization in exocyclic positions was considered. For the C-C

u bond energy, we employed the value 82.17 kcal/mole; for p unit, we used

the value 15.8 kcal/mole obtained from the correlation of experimental and HMO delocalization energies. In p units. In eV; the SCF calculations were undertaken with the parameters IC = 11.22 eV, YCC = 10.53 eV, and p& = -2.318 eV; W(D) were calculated by the standard SCF method of Pople, W(R') were calculated by the method of Lon uet Higgins and Pople. 'The experimental value of the dimerization enthalpy (159) is -47 kcal/mole.

With radical ions, the dimerization equilibrium is strongly influenced by the solvation and association of radical ions with counter ions. It has been shown that the free ions dimerize much more slowly than do the respective contact ion pairs: e.g., the quinoline radical anion does not dimerize in the powerfully solvating hexamethylphosphoramide, but it does dimerize rapidly in tetrahydrofuran (1 60). Thus, two equilibria should be distinguished (1 60), viz. and The former, which occurs in tetrahydrofuran, favors dimerization, while the latter, which takes place in hexamethylphoshoramide, is shifted far to the left. In spite of the complicating effects of solvation and association with counter ions, it appears that within a reaction series of conjugated radical ions, the following relation holds AGO = AW*MO + c, (1 10) where AG" means the free-energy change for the dimerization, AWHMo is the

RUDOLF ZAHRADN~K AND PETR

368

~ARSKY

corresponding HMO n-electron energy change defined by eq. (107), and C is a constant for the reaction series. In this way, McClelland (73) obtained interesting results on the dimerization of substituted ethylene radical anions which are consistent with the observed behavior (Table XIII). TABLE XI11 HMO Predictions for Dimerization Equilibria of Substituted Ethylene Radical Anionsa

AWHMo, p

Radical anion of Fulvene Styrene 1,l-Diphenylethylene Stilbene Triphen ylethylene Tetraphenylethylene

-.738 -2.084 -1.900 -3.308 -3.118 -4.102

Log Kb 57 -.7 (7)d -5 3 -45 -87

Observed behavior

Dimer Dime# Dimer Monomer Monomer Monomere

~

a From (73).

K is the equilibrium constant for the dimerization; log K values were estimated from the relation log K = -(AWHM0/2.303 RT) + D derived from eq. (107); assuming p = -2.54 eV and using the measured value of K for the dimerization of 1,ldiphenylethylene (K = 1.1 x l o 7 1. mole-' at 28"), one finds D = 87.9. Forms a polymer in the presence of excess styrene. b Experimental value, see footnote . Forms a dinegative ion.

Another type of interaction is the association of radical ions with the parent compounds. Recently (1 18), a theoretical study was reported on the interaction of butadiene ions with butadiene. Assuming a sandwich structure for the complex, the potential curve based on an extended Huckel calculation for two approaching butadienes (B + B) revealed only repulsion, as expected, while the curves for B + B+ and B t B- interactions exhibit shallow minima (.068 and .048 eV) at an interplanar distance of about 3.4 A . From CND0/2 calculations, adopting the parameter set of Wiberg (161), the dimer cation radical, Bz', appears to be .132 eV more stable than the separate B and B' species, whereas the separate B and B- species are favored by .116 eV over the dimer anion radical, B;. This finding is consistent with experimental results: formation of the dimer cation radical was proved in a convincing manner (162) while the attempts to detect the dimer anion radical have been unsuccessful. With other hydrocarbons, the reported formation of benzene dimer anion radical (163) represents an exceptional case, while the dimeric cation radical* was observed

* Both benzene dimer ion radicals were a subject of a recent theoretical study (166).

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

369

with a series of hydrocarbons (162, 164, 165). This observation can be qualitatively understood by considering the strong donor properties of aromatic hydrocarbons, which make coupling with cations feasible. On the other hand, the interaction with anions requires systems having a sufficiently high electron affinity: quinones and azines appear to be appropriate examples. Another type of dimer is that which consists of two radical molecules stacked on each other in a 77-77 interaction. Such dimers have been observed: e.g., with 9-ethylphenazyl radical, tetramethyl-p-phenylenediaminecation radical (1 67), 7,7,8,8-tetracyanoquinodimethaneradical anion (1 68), methylviologen cation radical (1 69), and 1-alkyl4-carbomethoxypyridinyl radicals (1 70). Attempts have been reported (170, 171) to interpret the electronic spectra of dimers of this kind by MO calculations. In radical chemistry, one often needs to estimate a priori a value of the disproportionation constant. Before attempting to d o this, let us start with the following consideration. In general, each closed-shell molecule can be converted to radical ions by a removal or an uptake of an odd number of electrons, and to polyions by a removal or an uptake of an even number of electrons. This statement can be expressed schematically as

where A stands for an organic compound. In a given medium, any of these systems can undergo other reversible or irreversible reactions, which will be disregarded here. The kinetic stability of ions can be anticipated to be lower the more remote the ion is from A. Thus, with most systems the most important equilibria are those underlined in eq. (1 11). With individual redox reactions, the following disproportionation equilibria can occur: K, . (1 12) A2"+A+2AAl, '

K2

A@t A" =+ 2 A,

for which [A']

K1 = [A2@][A]

[A'] K3

= [A2"] [A]

370

RUDOLF ZAHRADNfK AND PETR eARSKY

Assuming an ideal behavior for all components, K1, K z , and K3 become thermodynamic constants, for which we can write

-RT log Ki = AFi = AHi - TASi;

i = 1,2,3

(118)

On expressing Ki in terms of statistical thermodynamics, an approximation can be adopted that the partition function of the middle oxidation level is an average of functions for the oxidized and reduced forms: i.e., the preexponential Y d q e o;idation

Ki =

[ftfrfvl ftfrfv

level

e-~Hi/RT

ftfrfv

7

reduced form oxidized form

term in eq. (100) is equal to unity. Beyond doubt, this simplification applies considerably better in a gas phase than in solution, but for organic chemistry purposes, however, it can probably be used in solution also. Thus, AH is the only value to be estimated. Until now, the overwhelming majority of disproportionations of larger molecules studied have concerned conjugated systems. Since all respective oxidation levels possess the same number of (I bonds, consideration can be restricted to n-electron energies. In solution, however, solvation energy should be taken into account. First, let us discuss the case of reactions ( 1 12) and (1 14). For the disproportionation enthalpy, we can write AH = 2W' - W Z m -WA +2E:-EF

-@

(1 20)

where W and E s denote nelectron and solvation energy, respectively. This is a generally valid expression, in which the term concerning a n-electron energy change can be further simplified. Obviously, in the HMO approach the difference 2Wm- W2" - WA is identically equal to zero: m

E,+E,] i=l

-2

-1

1 Ei-2 i=l

m-I

Ei-2Em = O

(121)

i=l

(m denotes the singly occupied M O in a radical)

Hence, the HMO method is inherently incapable of giving any picture for disproportionation equilibria, the reason being the neglect of electronic repulsion. In the SCF treatment, it is convenient to assume that all three systems in the redox equilibrium are built up from the same MO's, the only difference being the number of IT electrons. Adopting this convention and denoting the oxidized form, radical, and reduced form as Ox, Sem (semiquinone), and Red, we can write

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

371

m-1

2 For 2We

-

c (2Jkm-Kkm)+Jmm

k=l

(127)

W2m - WA, the following simple relation is obtained (172): -AWSCF = Jmm

(128)

where J,, is the coulomb repulsion integral of the singly occupied MO in the radical Am: Jmm = SJpm (1 bm(2)

e2

7 ( ~ (lbm m (2) d71 d72 12

(129)

In the LCAO approximation

we can write

where yPv is an electronic repulsion integral in the A 0 basis. Eq. (128) affords apparently two interesting results: (a) Since Jmm is always greater than zero, in the gas phase, equilibria (112) or (114) should always favor the radicals; and (b) the larger the skeleton, the lower the value of J,, ; thus, more extensive 71 radicals should disproportionate more easily.

372

RUDOLF ZAHRADNfK AND PETR CARSKY

The disproportionation of radicals can occur only in solution. In polar solvents, it follows that E r +E$>2Eg;

EZetE$>2E;

(132)

Hence, the solvation energy change accompanying the disproportionation can compensate the repulsion term. In weakly solvating media, association with counter ions occurs and the disproportionation equilibrium should be considered, for example, as follows: 2 A ' - , N a + + A + A 2 - , 2Na'

(133)

Here, disproportionation produces a tight quadrupole A'; 2Na' which weakly interacts with the solvent, in contrast to the dipoles A'-, Na'. The gain of entropy resulting from the desolvation of ions becomes a driving force for disproportionation (1 73). In spite of the complicated nature of disproportionation equilibria, we values alone can give useful information on logK values think that the J,, through eqs. (120) and (1 28), because it appears that the enthalpy change, AH, accompanying disproportionation can be treated within many reaction series as

A H ,=, J +C (1 34) where C is a constant for a reaction series. As an example, we present data on 1,3,3-trimethylindolenin violenes (174) in Figure 15. It was found (175) with

10 log K

5

0

/

=4

I

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

313

violenes of various types that a Jmm value greater than 3.5 eV ensures the stability of radicals in the sense of eqs. (1 12) and (1 14). Eq. (1 13) represents another type of disproportionation equilibrium which, in contrast to the equilibria (1 12) or (1 14), involves two different radical ions. Here A H becomes

A H = 2 WA - W' - WQ+2 Ek- E: - Eg

(135)

For the n-electron change, AW, we obtain

and using Koopmans' theorem,

AWSCF = 2WA - W'

-

W6 = -I(A) t A(A) = &,

- I%,,,+

(137)

where I(A) and A(A) are the ionization potential and electron affinity, respectively, of the closed-shell form A, and &, and &,,+I are SCF orbital energies of the highest occupied and the lowest unoccupied orbitals, respectively, in A. Alternatively, A W can be expressed by the ionization potential and the electron affinity of radical ions A w S C ~= -A(A')

+I ( A ~

(138)

and evaluated on the basis of open-shell calculations on both radicals by combining eqs. (90), (96), and ( 1 38):

AWSCF = g m - g m + l

+$Jmm + $ J m + l , m + l

(139)

For naphthalene and anthracene, we calculated AWSCF both by eq. (137) and (139); the respective differences found were very little (.l and . 2 eV, respectively). If solvation is ignored, eq. (137) gives us an obvious result: viz., the recombination of radical ions is generally favored in disproportionation equilibria of this type. The respective A H is high enough t o populate one of the resulting A molecules in an excited state: therefore, in actual recombinations, A& + A' -+ A + A*, chemiluminescence is observed (176-180). This observation can be understood if eq. (137) is compared with the well known expressions for the lowest singlet-singlet and singlet-triplet SCF transition energies AES,-+m+,

-- $ m + l

AET,+m+,

-- $m+l - E m

-Em -Jm,m+l+2Km,m+1 - Jm,m+l

(140) (141)

Since Jm,m +, is always greater than zero, the A WSCF energy of recombination is generally greater than AET,,m+l and in many cases is probably also greater than AE;,,,,. This fact implies that the excitation should be feasible.

314

RUDOLF ZAHRADN~KAND PETR

CARSKY

Recently, a SCF intermolecular orbital theory was reported (181) which permits the calculation of the interaction energy of two closed-shell conjugated molecules for the initial stage of the reaction. Let E” be a n-electron energy of a resulting activated complex, and let EA and EA, be the n-electron energies of separate A and A‘ molecules; on the basis of second-order perturbation theory, the interaction energy can be expressed by the following equations (1 81):

where all primed and unprimed symbols refer to systems A’ and A, respectively, Z, are core charges, Rnp are the interatomic distances between position r and r’, q, are electron densities, S,; are overlap integrals between 2p, atomic orbitals located on nuclei r (on A) and r’ (on A‘), Aq, are charges (qr - Z,), j and k are indices running over occupied and unoccupied MO’s, respectively, and c denotes SCF expansion coefficients. The designation (rr’) means the summation over pairs of opposite atoms r and r‘ with directly overlapping orbitals, whereas rr‘ refers to the summation over all pairs. On adding odd electrons to A and A’ into their lowest unoccupied MO’s, one gets two radicals for which a similar expression can be derived (68):

where ELt is given by eq. (143). It should be stressed that eq, (144) was derived for the case of two identical radicals. We shall apply this expression to the dimerization of two benzyl radicals. First one needs to perform the SCF calculation on benzyl cation, and then one calculates Eint by means of

PHYSICAL PROPERTIES AND REACTIVITY OF RADICALS

315

eq$. (143) and (144) for several intermolecular separations in the range 2.5-5 A. The overlap integrals required can be taken from published tables (182). Figure 16 presents the dependence of the calculated interaction energy on intermolecular separation for several different orientations of two benzyl radicals. At larger distances, the sandwich configuration appears to be the most stabilized, while at separations less than about 2.9 8 , the most favored interaction is that leading to dimerization in the exocyclic positions. This indicates a possible reaction path: viz., the rotation around the axis determined by the exocyclic positions, permitting a change from the first to the second considered configuration.

P C

Figure 16. Interaction energy for two benzyl radical molecules approaching in two parallel planes as a function of the interplanar separation. Calculations (113) were b - - -, performed by means of eq. (141) for the following orientations: a -, c . . . . . . ., d _ . _ . - . - e --.., f - . . g - - . - -. -9

For neutral radicals, the most significant term in eq. (144) is that which is first order in the overlap. This term contains expansion coefficients of directly interacting positions where in dimerization a new u bond is formed. The higher the values of these expansion coefficients, the larger is the interaction energy, in accord with chemical anticipation for dimerization to occur in positions of the highest spin densities. With radical ions, also, the last terms in eqs. (143) and (144) are important, since they stand for coulombic interactions. Acknowledgment Calculations on normal vibration modes and partition functions were performed by Dr. Z. Slanina. His assistance is greatly appreciated. We wish also to express our appreciation to Mrs. R. zohov5 for helping us with preparation of the manuscript.

376

RUDOLF ZAHRADNfK AND PETR CARSKY

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A more complete coverage of the literature on electronic spectra of radicals is presented in our paper submitted for publication in Fortschr. Chem. Forsch. (Topics in Current Chemistry), where the ab initio studies are also reviewed and the existing open-shell computational procedures discussed. Recently we performed semiempirical all-valenceelectron calculations on ground-state properties and electronic spectra of small radicals (Zahradnik, R., and P. &sky, Theoret. Chim. Actu, 27, 121 (1972) and &sky, P., M. MachiEek; and R. Zahradnik, Coil. Czech. Chem. Commun., in press) and on equilibrium constants of dimerization reactions of small radicals (Zahradnik, R., 2. Slanina, and P. &sky, to be published).

Probing the Active Sites of Enzymes With Conformationally Restricted Substrate Analogs By George L. Kenyon and Judy A. Fee Department of Chemistry, University of California, Berkeley, California 94720

CONTENTS Introduction. . . . . . . . . . . . . . . . . Methods for Investigating Enzyme-Substrate (and Analog) Interactions Conformationally Restricted Nucleosides and Nucleotides . . . 1V. Conformationally Restricted Amino Acid Analogs . . . . . . V. Substrate Specificity of a-Chymotrypsin . . . . . . . . A. Incomplete Restriction of Locked Substrate Conformations . . B. Correspondence between Portions of Two Locked Substrates . C. Correspondence between Portions of a Locked and an Unrestricted Substrate . . . . . . . . . . . . . . . . D. Different Modes of Binding to the Enzyme . . . . . . . E. Size of Locked Substrates . . . . . . . . . . . . VI. Conformationally Restricted Active-Site-Directed Enzyme Inhibitors VII. Conclusions . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . .

I.

11. 111.

. . . . .

. . . . .

. .

. .

. . . . . .

. . . . . .

. . . . .

381 383 386 390 396 . 397 . 399

. . . .

400 401 402 402 407 407

I. INTRODUCTION Knowledge of an enzyme’s active site is fundamental to understanding the mechanism by which the enzyme acts as a catalyst, for it is at the active site that the substrate binds to the enzyme and is converted to product. The properties of the active site also determine the specificity of the enzyme. The specificity of an enzyme is therefore intimately tied up with the detailed chemical mechanism of the catalytic process. In a sense, defining an enzyme’s specificity is analogous to defining the scope of a nonenzymatic chemical reaction. One of the first tasks one has in undertaking a mechanistic study of a nonenzymatic process is to discover which types of compounds undergo the reaction and which d o not. Often, mechanistic clues arise from such investigations. The same principles apply (or should apply) to the study of the mechanisms of enzyme action. 381

382

GEORGE L. KENYON AND JUDY A. FEE

Specificity studies, whlch involve the use of substrate analogs, are then one type of probe of the active site.* Indeed, all methods for probing the active site, including the most recently developed physical methods such as X-ray analysis and nmr spectroscopy, involve the use of the substrate or substrate analogs to point out the location of the active site. Thus, the study of enzyme mechanisms stands to benefit greatly from organic chemists who choose to synthesize new substrate analogs. Analogs of substrates may be active substrates themselves (sometimes called pseudosubstrates), inhibitors of the normal enzymatic process, or neither active substrates nor inhibitors. Useful information can be gained from all three types of analogs. Substrate analogs which promise to be particularly good active-site probes are those which are conformationally restricted. One key feature of enzymatic processes is that when a substrate is bound to an enzyme, probably only one of the many possible conformations of the substrate molecule is assumed. Consequently, before a detailed mechanism for an enzymatic process can be formulated, the preferred conformations of each of the enzyme-bound substrates must be known.** Substrate analogs which are already restricted to a particular conformation (or at least restricted to a limited range of conformations) are then useful in unraveling details about the specificity, preferred geometries for the substrates at the active sites, and aspects of the catalytic mechanism from a physical organic point of view. Conformationally restricted analogs generally are locked by having one or more new small or medium-sized rings bridging between (or among) different parts of the normal substrate molecule. Some exceptions to this definition will be discussed later (e.g., 8-bromoadenosine). The purpose of this review is to discuss a selected number of cases where such “locked” substrate analogs have been used, representing a range of types of common, naturally occurring substrates. There are some problems involved in the use of conformationally restricted analogs. For example, some enzymes appear to be so highly specific

* It is useful to differentiate between substrate specificity, which is the inclination of the given enzyme to react more efficiently with (or, in some cases, bind more tightly to) some potential substrates than others, and product specificity, which is the inclination of the enzyme to transform the substrate into only one (usually) of many possible isomeric products. As a consequence of the principle of microscopic reversibility, for a reversible reaction, product specificity for the reaction in one direction becomes equivalent to substrate specificity in the other direction. ** Strictly speaking, the conformations and relative geometries of the reactants must be known over the entire reaction coordinate: moreover, there are indications that the transition states in enzyme reactions, which often have very different preferred conformations from those of the bound substrates, may be more tightly bound to the enzyme than either the starting materials or the products (1).

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

383

for their natural substrate that even relatively minor perturbations on the substrate's structure obliterate both binding to the enzyme and activity in the reaction catalyzed by the enzyme. However, when examined with closely related analogs, some enzymes which were once thought to be highly restrictive with respect to substrate specificity [e.g., creatine kinase from rabbit muscle (2)] have been found to be not so restrictive after all. Also, tying together two portions of a substrate molecule into a ring, for example, often adds little or no extra bulk to the structure. Besides this problem of designing conformationally restricted analogs for highly specific enzymes, there are 0 ther problems to be considered in dealing with less specific enzymes. These are discussed later in the section on locked a-chymotrypsin substrates. Despite these problems, the potential of research with conformationally restricted substrate analogs appears t o be great. As yet, the use of these analogs with tools other than steady-state kinetics has been little explored.

FOR INVESTIGATING ENZYME-SUBSTRATE (AND ANALOG) INTERACTIONS

11. METHODS

A variety of methods are now available for investigating the intricacies of enzyme-substrate and enzyme-analog interactions. In screening for interesting analogs, one can learn much by investigating steady-state kinetic parameters for" a given analog and comparing these parameters [e.g., maximal velocity, the ,,) and velocity at saturating substrate concentrations (usually abbreviated V the Michaelis constant, the substrate concentration at one half maximal velocity (usually abbreviated Km)] with those for the natural substrate. In the absence of a relatively detailed knowledge of the overall kinetic scheme characteristic of the enzymatic reaction being studied, however, considerable caution must be exercised in interpreting rigorously the meaning of these parameters. For example, the observed Km value can be greater than, equal to, or less than the true binding constant for the enzyme-substrate complex, depending on the kinetic scheme (3). Kinetic studies are often very useful in categorizing inhibitors: for example, inhibitors may be competitive with respect to the substrate, uncompetitive, or noncompetitive (4). For many enzymes, the kinetic behavior of an inhibitor can be studied to confirm or deny a given hypothesis about the mode of inhibition. Excellent reviews of enzyme kinetics, including ways of recognizing the major common types of kinetic schemes, have appeared recently in treatments by Cleland (5-9), Mahler and Cordes (4), Westley (3), and Plowman (10). More detailed knowledge about individual steps in enzyme kinetic schemes must generally be sorted by use of such rapid measurement techniques as stopped-flow and temperature-jump methods. Recent progress in

384

GEORGE L. KENYON AND JUDY A. FEE

these areas also has been reviewed [see, for example, reviews by Eigen (1 I), Hammes and Schimmel(l2) and the volume edited by Kustin (1 3)] . Recently, Gass and Meister (14) have developed computer techniques for analyzing results obtained from kinetic measurements on the glutamine synthetase reaction with a variety of analogs of the substrates, particularly analogs of D and Lglutamic acids. In essence, the computer program was designed to manipulate the coordinates of molecules: e.g., “rotation, translation, rotation of a part of a molecule around a given bond, and finding the position of an atom such that the distance from this atom to a given point is at a minimum” (14). Given sufficient information, the program both allows an estimation of the preferred conformation of the substrate when bound to the active site of the enzyme and helps to define regions in the space around the normal substrate where substituents can be tolerated without severe loss of activity. The latter type of information is clearly very valuable in designing conformationally restricted analogs. Prelog and his co-workers also have used computer analysis of kinetic data in investigating the specificities of a range of less highly specific alcohol dehydrogenases (1 5). One of the most exciting approaches to the investigation of enzymesubstrate complexes is the use of X-ray diffraction techniques and, in particular, the use of difference Fourier analysis, which potentially allows a range of enzyme-substrate complexes t o be examined while avoiding the necessity of solving the entire enzyme’s structure each time. A major limitation to the bfference Fourier method is the necessity of obtaining crystals of the enzyme-substrate complex which are essentially isomorphous with those on which the original structural determination was performed (16). The method employed for preparing these isomorphous replacements is to diffuse the substrate (or substrate analog) into the intact crystal lattice (16). In preparation of this type of enzyme-substrate complex for X-ray studies, only relatively poor substrates can be used, since otherwise the enzyme will catalyze transformation of the substrate before the structure can be determined. Another potential limitation with regard to mechanistic significance is that one worries about the relationship between the structure of the protein in the crystalline state versus that in solution, where catalysis is normally observed. Some artifacts of the crystalline state have been reported (16). On the other hand, there is good evidence that some enzymes are still viable catalysts in the crystalline state, at least those molecules of these enzymes that are at or near to the crystal’s surface (1 7-20). The successful use of these X-ray crysallographic techniques in studying the enzyme-substrate interactions of lysozyme (2 1) and chymotrypsin (22) has recently been reviewed by Blow and Steitz (16) and Blow (23). To date, however, these methods have had only limited application, since the detailed structures of only about ten enzymes have been elucidated by X-ray diffraction

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

385

techniques. One related problem is that in the absence of independent knowledge of the linear amino acid sequence (the primary structure), which is still a long, tedious task to unravel, only about 60%of the amino acid residues of a typical enzyme can be assigned with certainty by use of X-ray diffraction information at 2.0 A resolution (16). A wide variety of other techniques have been applied to the study of enzyme-substrate interactions (24). We are particularly interested here in methods that give reasonably detailed structural information about enzymesubstrate complexes. The potentialities of a relatively new approach to this problem, the use of nuclear magnetic resonance (nmr) spectroscopic methods, have just begun to be appreciated. The pioneering work of W. D. Phillips and his group (25) and Jardetzky and his co-workers (26-28) on proton nmr studies of lysozyme and ribonuclease, for example, have already been very useful in relating aspects of specificity to mechanism. Recently Cohn and her co-workers (29) have reported on a different approach, which again uses mainly nmr spectroscopy. When paramagnetic probes, such as certain metal ions and spin labels (30), are bound to the enzyme to effect line-broadening of proton nmr signals, it is possible to calculate specific interatomic and intermolecular distances (e.g., distance from a fixed spin label or metal ion t o a given proton of a substrate bound to the active site). This procedure allows the “mapping” of the relative geometries and positions of the substrates at the active site (29). The advantages of this method over that of X-ray crystallography are that measurements are made in dilute, aqueous solution and results are more quickly obtained. So far, the technique has been limited to those enzymes which utilize (or can utilize) a paramagnetic metal ion in the normal enzymatic process and where a spin label has been introduced into the active-site region. Moreover, since the currently available spin labels are such relatively large molecules, one worries about the extent to which these labels perturb the normal structure of the enzyme around the active site. A common feature of the above different approaches is that for the study of any given enzyme, effective use can be made of a relatively wide variety of reactive, inhibitory, and inert substrate analogs. For example, Steitz, Henderson, and Blow (22), in constructing their detailed model of the active site of a-chymotrypsin based on X-ray crystallographic information, made extensive use of the specificity results of several research groups. In particular, they made good use of conformationally restricted, structurally well defined substrate analogs such as D1-keto-3-carboxy-l,2,3,4-tetrahydroisoquinoline, 24, of Hein, McCriff, and Niemann (3 1) and the 2,2’-bridged bicyclic analog of benzoyl-L phenylalanine, 25, of Belleau and Chevalier (32). In the following sections, we shall present some selected cases where conformationally restricted substrate analogs have been used to obtain valuable information about various enzymatic processes.

386

GEORGE L. KENYON AND JUDY A. FEE

111. CONFORMATIONALLY RESTRICTED NUCLEOSIDES AND NUCLEOTIDES In recent years, researchers in the area of nucleoside- and nucleotide-requiring enzymes have begun to wonder about the preferred conformation of the purine or pyrimidine moiety relative to the ribose portion of the molecule when the substrate is bound to the enzyme in its most reactive form. The two extreme conformations for the adenine group of adenosine, for example, are shown in structures 1 (R = H) and 2 (R = H). In structure 1, the bulk of the adenine ring is turned away from the 5' OR group of the ribose. This conformation is called anti (33). In structure 2, the adenine group is rotated 180' about the bond to the ribose 1' carbon relative to that in structure 1, and the conformation is called syn (33). The same syn and an?i designations have been given to pyrimidine nucleosides and nucleotides where, in analogy to the case for the purine ring, the more bulky portion of the pyrimidine ring is turned away from the 5' OR group of the ribose in the anti conformation.

2

1

4

3

0,

0

5

/

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

387

There is strong chemical evidence that most nucleosides and nucleotides prefer the anti conformations in the absence of enzymes. A number of X-ray crystallographic studies, for example, have shown that in the crystalline state, the anti conformation is nearly always observed for the naturally occurring nucleosides and nucleotides (33-36). Two exceptions are adenosine 3’,5’-cyclic phosphate, both conformations of which were found t o exist simultaneously in the same crystal structure (37), and deoxyguanosine, which showed the syn conformation in a deoxyguanosine : bromodeoxycytidine crystalline complex (38, 39). Studies of 5’-linked nucleotides in solution by nmr spectroscopy also have provided evidence for the preference of the anti conformation (40, 41). Other considerations (33) indicate that the energy barrier between the syn and anti forms of naturally occurring purine nucleosides is not so great as that for the pyrimidine nucleosides, which show a more pronounced preference for the anti conformation. In the case of the pyrimidine nucleoside 4-thiouracil, however, the syn conformation was found in the crystalline state (42). Similarly, the synthetic purine nucleosides 8-bromoadenosine, 4, R = H, and the structurally similar 8-bromoguanosine both recently were found by Tavale and Sobell to be in the syn conformations in the crystalline state (43). Careful model building had earlier suggested that close steric contacts introduced by the

‘N’

y & * 3 $ 1 \ P

0

6

7

P

8

9

388

GEORGE L. KENYON AND JUDY A. FEE

relatively bulky bromine atoms on these two nucleosides effectively exclude the normally energetically more favorable anti conformations (43, 44). Thus, it is a reasonable hypothesis that purine nucleosides and nucleotides with substituents on the 8 position approximately as bulky as a bromine group or larger effectively “lock” the analog into the syn conformation. Recently, the syntheses of some purine nucleosides locked into anti-type conformations have been reported: e.g., 3 (49, 6 (47), 7 (48) and 8 (49). A characteristic of these analogs is that the planes of the adenine rings are in rather rigidly fixed positions relative to the “plane” of the five-membered ring of the ribose. A diagram showing the approximate fixed angles of the purine group bridging to the 2’, 3‘ and 5’ positions, respectively, of the ribose, similar t o that given by Ikehara (46), is illustrated below.

There is convincing evidence that many purine nucleoside- and nucleotiderequiring enzymes prefer to act upon the anti conformation of the substrate. One of the most thoroughly studied enzymes with respect to nucleoside specificity is adenosine deaminase from calf intestine. Simon, Bauer, Tolman, and Robins (50)studied the specificity of the enzyme with a series of analogs of adenosine substituted in the 8 position of the adenine ring with amino, 0x0, methyl, bromo, thio, methyloxy, or ethylamino groups. Whereas the 8-amino and 8-0x0 derivatives were slowly reacting substrates, none of the others with more bulky substituents was reactive. More recently, Ogilvie, Slotin, and Rheault (49) have prepared the adenosine analog 8 (R = H), which also contains a bulky substituent in the 8 position but is locked into an anti-type conformation. They found that the analog was a reasonably good substrate for the adenosine deaminase, having a V,,, of 7% of that of adenosine itself. Based on this result and the results of Simon, Bauer, Tolman, and Robins, they postulated that the enzyme requires the anti conformation for activity of the nucleoside (49). Preliminary results of Hampton and his co-workers substantiate this proposal: analog 3, locked into the anti conformation, is an even better substrate for adenosine deaminase than 8 (46). Similarly, Ikehara, Tazawa, and Fukui (51) have found that the nucleotides 8-bromo and 8-oxoadenosine 5’-diphosphate, 8-bromo-, 8-0x0, and 8-dimethylaminoguanosine 5’-diphosphate are all inactive as substrates for homopolymer synthesis catalyzed by polynucleotide phosphorylase from Escherichia coli. Some of these results were later confirmed by Kapuler, Monny, and Michelson ( 5 2 ) , who found that neither 8-bromo- nor 8-oxoguanosine 5’-diphosphate was active as a substrate for homopolymerization with polynucleotide phosphorylases isolated both from A zotobacter vinelandii and E. coli.

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

389

They did find that these compounds behaved kinetically as competitive inhibitors of polymerization of the normal substrates: e.g., guanosine 5’diphosphate. These authors suggested that the successful completion of the polynucleotide phosphorylase reaction requires that the nucleotide be capable of assuming the anti conformation. Also, Kapuler and Reich (53) have found that both 8-bromo- and 8-oxoguanosine 5’4riphosphates are very poor substrates in the E. coli RNA polymerase reaction and are com.petitive inhibitors with respect *, to guanosine 5‘4riphosphate as a substrate. Finally, the pyrimidine nucleotide 4-thiouridine 5’-triphosphate, also presumably essentially in the syn conformation, cannot serve as a substrate for homopolymerization with E. coli RNA polymerase (54). Small amounts of 4-thiouridine were reported to have been found in naturally occurring transfer RNA from E. co2i (55). Scheit has reported that as a monomer in CDC13, the base can still pair with adenosine (56). Clearly, more systematic studies with various enzymes using nucleoside and nucleotide analogs of both types, those locked in the syn and those locked in the anti conformations, are needed to test more rigorously these hypotheses about conformational preferences. What is especially needed is a purine nucleoside or nucleotide which is more securely restricted to the syn conformation. The hypothetical adenosine analog 5 , in which two methylene groups bridge between the C-1’ of the ribose and the 8 position of the adenine, appears to us from model building to be both relatively rigid and strain free. Since at least some nucleoside- and nucleotide-requiring enzymes can tolerate some bulk on the 8 position of the adenine and still show activity ( S O ) , we feel that compound 5 could be valuable as a example of a locked syn adenosine analog. Yet another fundamentally different type of conformationally restricted nucleotide is Eckstein’s uridine 2’,3’-O,O-cyclophosphorothioate anion, 9, a thio analog of uridine 2’,3’-O,O-cyclophosphateanion, which is a known substrate for bovine pancreatic ribonuclease (57). It is well established that in the mechanism of action of pancreatic ribonuclease, the ribonucleic acid (RNA) is broken down in two steps, the formation of a 2’,3‘-cyclic phosphate intermediate and the subsequent hydrolysis of this cyclic phosphate (58). The thio analog 9 is especially interesting since not only is it already locked into the structure of the proposed intermediate, but also the presence of the sulfur atom generates a new asymmetric center a t the phosphorus and thus provides a basis for answering questions about the stereochemistry and mechanism of attack at the phosphorus. The analog has two diastereoisomeric forms, differing in the configuration about the phosphorus. These forms have now been separated (57), and the structure of one of these diastereoisomers has been determined by an X-ray crystallographic study (59). The P-S bond length is consistent with its having double-bond character, and the negative charge appears to be localized on the free oxygen atom of the phosphorothioate group (59).

390

GEORGE L. KENYON AND JUDY A. FEE

When 10 (R configuration about phosphorus) was treated with ribonuclease in aqueous methanol, nucleophilic attack by methanol in the enzyme-catalyzed process led to formation of a methyl ester, 1 1, which has been shown by X-ray analysis to be the isomer with the R configuration about the phosphorus (60):

___* RNase

aq. CHI OH

0 0

I

'%

$'

",P "

II

S 10

Ho-cw H

9

0-H

',,

CH,O-P -Oe

II

S 11

This result corresponds to a net inversion of configuration at phosphorus and is in accord with the postulated "in-line'' mechanism. This path was earlier demonstrated to be the preferred stereochemical course for the enzymecatalyzed process by Usher, Richardson, and Eckstein (61), who determined the configuration of the product of 10 with ribonuclease-catalyzed attack by "0-enriched water. In the "in-line" mechanism, the attacking methanol or H2" 0 presumably goes to an apical position of a trigonal-bipyramidal intermediate, the two oxygen atoms in the five membered phosphoruscontaining ring bridge between an apical and an equatorial position, and this apical ring oxygen is the leaving group in the subsequent breakdown of this intermediate (61). No pseudorotation is indicated, since it would lead to retention of configuration at phosphorus (62). Supporting evidence that n o pseudorotation occurs came from experiments which showed that during enzymatic hydrolysis of either diastereoisomer of 9 there was no exchange of sulfur, as shown by using "S-labeled substrates (57). These results contrast sharply with those obtained in the nonenzymatic, acid-catalyzed hydrolyses of these same diastereoisomers, in which considerable exchange of sulfur by oxygen was observed (63). These findings are consistent with postulated pentacovalent phosphorus intermediates involving pseudorotational conversions for these nonenzymatic reactions. This work o f Eckstein, Usher, et al., is an example of the use of a conformationally restricted analog to give information about the product specificity (see Introduction) of an enzyme which could not be obtained from the natural substrate.

IV. CONFORMATIONALLY RESTRICTED AMINO ACID ANALOGS As mentioned in Section II., Meister and his co-workers (64) have studied extensively the substrate specificity of the enzyme glutamine synthetase from

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

391

sheep brain, particularly with respect to the substrate glutamate, 12. They have used a conformationally restricted analog of glutamate to provide experimental evidence both for the postulated conformation of glutamate at the active site and for a proposed intermediate in the reaction catalyzed by the enzyme: Mg'

+

L-glutamate t NH3 t ATP i L-glutamine t ADP +inorganic phosphate The specificity results of Meister et ul., obtained on conformationally nonrestricted glutamate analogs, are consistent with the hypothesis that the carbon chain of Lglutamate is oriented on the enzyme in the fully (or almost fully) extended conformation depicted in 12 (14). Moreover, they found that replacement of either the a-hydrogen or the y-threo hydrogen (indicated by bold arrows above structure 12) by a methyl group does not prevent reactivity in the glutamine synthetase reaction: that is, a-methyl-Lglutamate and threo-ymethyl-Lglutamate are both active substrates (64). However, erythro-ymethyl-Lglutamate , a-methyl-Dglutamate, and y-me t hyi-Dglutamate are not active as substrates. From these observations, it appeared that the locked substrate analog Lcis-l-amino-l,3-cyclohexanedicarboxylic acid 1 3 could also be a substrate for this enzyme (cf. structures 12 and 13) and that the corresponding trans isomer could not be.

13

Cis- and trans-D,Ll -amino-l,3-cyclohexanedicarboxylic acids were therefore synthesized and tested as substrates for the enzyme (65). The D,Ltruns compound, like its open-chain analog erythro-y-methylglutamate, was unreactive; but close to 50% of the added D,Lcis compound acted as a substrate. Gass and Meister ( 6 5 ) have tentatively assumed that the Lenantiomer is the substrate because of the unreactivity of a- or y-methyl-Dglutamate. The V , and K, values of this locked substrate are similar to those of Lglutamate. Its reactivity gives further evidence that glutamate is in a fully extended conformation at the active site and indicates that the region occupied by ring

392

GEORGE L. KENYON AND JUDY A. FEE

carbons 4, 5, and 6 is directed away from the enzyme's surface. It is possible that 13 reacts in the less stable conformation in which both carboxylate groups are axial. However, the diequatorial conformer (corresponding to the fully extended form of glutamate) is favored in conjunction with results on other analogs (65). In subsequent experiments (66), this locked substrate was used to obtain evidence for the hypothesis (67) that enzyme-bound y-glutamyl phosphate 14 is an intermediate in the enzyme-catalyzed reaction. All attempts to isolate this acyl phosphate 14 have failed (66), presumably because of the marked tendency of this intermediate to cyclize to pyrrolidonecarboxylic acid, 15, and to hydrolyze to glutamic acid. 0 H,$-CH-CH, I COOe

I1 -CH, -C-O-PO,H~

HoocQo H

14

I H

15

This cyclization would involve intramolecular attack by the a-amino group of 14 on the carbonyl of the acyl phosphate moiety. The substrate analog 13, on the other hand, is locked in such a fashion that the acyl phosphate derived from it, shown as structure 16, should be much more stable, since the a-amino group is held away from the carbonyl of the acyl phosphate moiety and a similar intramolecular attack is precluded. Taking advantage of this anticipated extra stability, Tsuda, Stephani, and Meister (66) recently have incubated D,Lcisl-amino-l,3-cyclohexanedicarboxylicacid, ATP, and metal ion with glutamine synthetase (note that the ammonia was omitted) and have succeeded in isolating a compound with properties consistent with those expected for acyl phosphate 16. This procedure is then an example of the use of a conformationally restricted substrate analog in allowing the isolation of an otherwise unstable intermediate in an enzymatic reaction. In our laboratory, we have focused our attention on the syntheses of various analogs of creatine, 17, a substrate for the enzyme creatine kinase from rabbit muscle (2). The reaction catalyzed by this enzyme is

17

1

Md

a

YH3

NH2

.p

0 , C -C H ,-N =C.,

+

(3

NHPO,HQ

+ ADP

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

393

There is good evidence that the enzyme follows a rapid equilibrium, random, bimolecular, bimolecular kinetic scheme in which the reversible interconversion of the enzyme-creatine-MgATP ternary complex and enzyme-phosphocreatineMgADP ternary complex is rate limiting (68, 69, 70). A list of values of V,,, (relative to creatine) and K, for some of these creatine analogs is given in Table I. From these results and the results of Cohn and her group from mapping the active site of creatine kinase by nmr spectroscopy as discussed in Section lI., the preferred conformation for creatine bound to the enzyme shown in structure 18 is hypothesized. The arrows point to positions on the structure where methyl groups may replace hydrogens without severe loss of reactivity. Five conformationally restricted analogs of creatine now have been prepared. These are DN-amidinoproline, 19; LN-amidinoproline, 20; 1-carboxymethyl-2-iminoimidazolidine,21; I-carboxymethyl-2-iminohexahydropyrimidine, 22; and D,L3-methyl-4-carboxy-2-iminoimidazolidine (the L enantiomer is depicted in structure 23).

18

21

19

23

Both the LN-amidinoproline, 20, and 1-carboxymethyl-2-iminohexahydropyrimidine, 22, are only marginally reactive at best as substrates for the enzyme (2,71), and 20 is also poorly bound (71). Also, preliminary investigations 23 is not very have shown that D,L3-methyl-4-carboxy-2-iminoimidazolidine reactive as a substrate for the enzyme (72). As shown in Table I, the DN-amidinoproline, 19, although not a very reactive substrate, is considerably more reactive than the L enantiomer. Assuming that the methylene groups of the five-membered ring prefer to project into the hydrophobic region of the enzyme normally binding the N-methyl group of creatine itself (71), then creatine would appear to prefer the conformation shown in structure 18. The fact that 1-carboxymethyl-2-iminoimidazolidine, 2 1, is such a good substrate supports this postulate (71). That D,L23 is a poor analog serves to reinforce the idea that only one

P

\o

w

I

OzC--CHZ-N

W

NH

63

/NHZ

NHZ

.JW

4c-k.

OzC-CHZ-N=Ck.

CH3

1Carboxymethyl-2-iminoimidazolidine

Creatine (N-methyl-N-amidinoglycine)

Name

*NHz

I

H NHZ

NHZ

NHZ

~o,c-cH,-N=c<

CH3

I

Glycocyamine (N-amidinoglycine)

Q ~ z ~ - ~ ~ - ~ = ~ < D,L-N-Methyl-N-amidinoalanine

I

CH3

NH2

CHZCH, I -2NHz e ~ , ~ - ~ ~ , - ~ - ~ k .N-Ethyl-N-amidinoglycine

€3

Q

Structure

TABLE I

10

24

32

90

100

Relative Vmax (T = 1") (%, in order of decreasing reactivity)

Some Kinetic Parameters for Analogs of Creatine in the Creatine Kinase Reaction (71)

12 mM

71 mM

47 mM

25 mM

5 mM

Km (T = lo)

(h

W W

\

N-Methyl-N-methylamidinoglycine

L-N-Amidinoproline

I

)

l-Carboxymethyl-2-iminohexahydropyrimidine These three analogs were very slowly reacting substrates a t best (relative Vmax 5 .l%)

230 mM

N-Methyl-N-amidino-p-alanine

53 mM

100 mM

1 .o

D-N-Amidinoproline

N-propyl-N-amidinoglycine

396

GEORGE L. KENYON AND JUDY A. FEE

region around the bound creatine can tolerate alkyl substituents (71). Some of these ideas about preferred regions in space where substituents on the creatine can be tolerated are being tested in collaboration with Cohn and her group with use of the previously described nnir mapping procedures with some of these analogs. In contrast to the others shown in Table I, analog 21 is an excellent substrate for the enzyme, having a V,, of 90% of that of creatine itself. Unlike creatine, which has a plane of symmetry making the two primary guanidino nitrogens equivalent, 21 has the two corresponding guanidino nitrogens differentiated, one being primary and the other being secondary. When 21 was phosphorylated in the creatine kinase-catalyzed reaction and the product was isolated and characterized by nmr spectroscopy, it was shown that only one guanidino nitrogen was phosphorylated (2). This result strongly implies that creatine itself is phosphorylated on the corresponding guanidino nitrogen when the substrate is bound to the enzyme. In this case, the conformational restriction serves to differentiate between two otherwise equivalent portions of a substrate so that the product specificity of the enzyme can be investigated,

V. SUBSTRATE SPECIFICITY O F a-CHYMOTRYPSIN a-Chymotrypsin from bovine pancreas normally catalyzes the hydrolysis of peptide (amide) linkages, especially efficiently at the carbonyl groups of aromatic amino acid residues (23). The enzyme is relatively nonspecific and also catalyzes ester hydrolyses, particularly of esters of aromatic acids (23). It is probably the most thoroughly studied of all known enzymes with respect to specificity. The X-ray crystal structures of both the enzyme and an enzymesubstrate complex with N-formyl-Ltryptophan have been elucidated (20). Based on their specificity studies, Hein and Niemann (73) presented a theory of a tetrahedral binding site for the substrate on the enzyme. A similar theory has been presented by Cohen (74). Briefly, the theory is that the enzyme has special binding subsites, in addition to the catalytic site, for the aromatic amino acid side chain, for the acylamido group, and for the a hydrogen of a natural substrate (i.e., a substrate having the L configuration). The X-ray crystallographic studies agree in general with this theory, but they do not substantiate Cohen’s idea of a restricted binding subsite for the a hydrogen (23). Use of conformationally restricted substrate analogs for investigating the substrate specificity of cw-chymotrypsin provides an instructive example of the difficulties encountered in interpreting the results of such experiments, difficulties which, as we shall see, are especially severe for relatively nonspecific enzymes.

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

397

The substrate analogs with which we shall be concerned are alike in that they are esters or amides of aromatic compounds whose atoms have been locked into heterocyclic ring systems. Because many of these locked analogs have already been discussed in Blow’s review (23), it is worthwhile here t o concentrate mainly on only two: D1 -keto-3-carboxy-l,2,3,4-tetrahydroisoquinoline, 24, studied by Hein and Niemann (31, 75), and the 2,2’-bridged biphenyl analog of N-benzoylphenylalanine methyl ester, 25, studied by Belleau and Chevalier (32). A comparison of the behavior of these compounds with a-chymotrypsin brings out some ambiguities involved in inferring the preferred conformations of nonrestricted substrates when they are bound to the enzyme from those of locked substrates. Some of these ambiguities will be discussed in the following sections. L: R = H ; R ’ = COOCH, D: R = COOCH,; R’

=

H

9

N ,\,.COOCH,

R,

24

\ /

A. Incomplete Restriction of Locked Substrate Conformations The conformations of the “locked” substrates may be only partially restricted. Indeed, this is the case for many locked substrates. Neither of the substrate analogs under consideration, for example, is restricted to only one conformation. The conformation of 25 which is active with a-chymotrypsin, however, is reasonably well known, whereas the active conformation of 24 is still controversial. Analog 25 exists primarily in two slowly interconvertible forms: conformer R-Sa, 26, in which the biphenyl system has the R configuration and the carbomethoxy group is axial to the eight-membered ring, and conformer S-Seq, 27, in which the biphenyl system has the S configuration and in w h c h the carbomethoxy group is equatorial. The R-Sa form, stable in the crystalline state, slowly converts to the S-Seq form in solution, as shown by changes in optical rotational strength at 252 nm and in the nmr spectrum: i.e., the methoxy group protons of the R-Sa form absorb at 63.69 and the corresponding protons of the S-Seq form absorb at 63.81. It is apparently the latter form that is hydrolyzed in the presence of the enzyme, since no hydrolysis occurs when the R-Sa form is first dissolved, and the rates of enzymatic hydrolysis and isomerization, measured independently, are identical (32). Since there are no comparable methods for determining the preferred conformation of 24 when it reacts with the enzyme, researchers in the field are

398

GEORGE L. KENYON AND JUDY A. FEE

36

divided as to whether the carbomethoxy group is axial or equatorial (23). The main basis for arguing in favor of the substituent being equatorial is the relative enzymatic reactivities of certain cis and trans isomers of p-nitrophenyl esters of t-butylcyclohexanecarboxylic acids (76). Based on their theory about the binding subsites on the enzyme, however, Hein and Niemann have argued in favor of an axial carbomethoxy group. Awad, Neurath, and Hartley (77) also have argued that since the axial forms of D and L24 are less alike than the corresponding equatorial forms, invoking preference for the axial substituent helps account for the much greater reactivity of the D enantiomer compared to the L enantiomer (rate ratio 4000 : 1). Lawson (78) at first favored an axial substituent because of the unreactivity of the planar compound methyl coumarilate, 28, in comparison to the substrate methyl Dhydrocoumarilate, 29; he suggested that planar compounds are more similar to the equatorially

28

29

substituted 24 than to the axial conformer. Later he retracted his argument (79). In fact, the nearly planar carbomethoxyisocarbostyril, 30, is a substrate for the enzyme (75). More recently, X-ray diffraction analysis of the N-formyl-L tryptophan-enzyme complex suggests that the equatorial conformer would be

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

399

&" ' n

COOCH,

30

preferred (20,23). The arguments in this axial-equatorial controversy are based primarily on the behavior of compounds not clearly related to 24, and the controversy obviously has not been resolved. The possibility remains, of course, that the reactive conformation of 24 is one in which the carbomethoxy group is in an intermediate position between the two extremes (78).

B. Correspondence between Portions of Two Locked Substrates According to the postulate that there is but one reactive conformation of a substrate, the preferred conformations of the two locked a-chymotrypsin substrates 24 and 25 should at least be rather similar. One way to compare their conformations is to look along the bond connecting the /3 carbon to the phenyl ring, as shown in structures 31ax, 31eq, and 32. If both analogs are considered to be N-acylated derivatives of phenylalanine, then the phenyl groups of each should have the same relationship to both the catalytic site and the acylamido binding site. Both 32 and the axial conformer 31ax have carbomethoxy groups positioned above the plane of the ring; but the bond from the carbomethoxy group of the axially substituted 31ax to the a-carbon is perpendicular to the phenyl ring, whereas the analogous bond in 32 is almost parallel to it. In addition, the carbomethoxy group of the latter is farther from the phenyl ring: it extends back into the plane of the page in structure 32. Moreover, the acylamido groups cannot be in similar positions in the two compounds because the configuration about the a carbon is L for one and D for the other. The groups around the a and /3 carbons are staggered in either the axial or equatorial conformations 31ax and 3 leq. A conformation intermediate between axial and equatorial has eclipsed groups, as does 32.

32

31ax

31eq

One possible conclusion to be drawn from this cottiparison is that there is not one single conformation that is reactive with the enzyme, but a range of conformations. The flexibility of positioning of some portions of the molecule,

GEORGE L. KENYON AND JUDY A. FEE

400

such as the acylamido group, may be greater than that for others. On the other hand, this conclusion is not valid if portions of the two molecules being compared are not analogous. This problem is discussed in the next section. Furthermore, the conclusion may not be applicable to unrestricted substrates because of binding differences, a problem discussed in a later section. C. Correspondence between Portions of a Locked and an Unrestricted Substrate No compound other than the methyl ester of N-benzoyl-Lphenylalanine, 33, is an obvious choice for an open-chain analog of the locked substrate 25; but D24, on the other hand, may be a locked analog of either N-benzoyl-Dalanine methyl ester 34 or of N-formyl-Dphenylalanine methyl ester 35 (75). If 24 is an analog of 34 rather than 35, the comparison of the two locked analogs made in Section V.B. is not valid: the phenyl of 24 would then correspond to the benzoyl phenyl of 34.

/H

o

COOCH,

/ \ -

33

&H

\

'

&H H

H,C

, A H

34

,\'

\

COOCH,

COOCH,

35

Such a comparison is made in structures 27 and 36. This parallel is attractive because the location of the acylamido group is approximately the same in both of the compounds when the bonds from the (Y carbons to the carbomethoxy group are in corresponding locations. In addition, the phenyl group of 36 is held forward from the plane of the page, as is the benzoyl phenyl of 27, whether the carbomethoxy group is axial or equatorial. The phenyl ring of axial 36 is more nearly in the same position as that of 27, but the acylamido group of equatorial 36 is closer to that of 27 than is the acylamido group of the axial compound. In contrast to 36 (representing D24), the phenyl portion of the enantiomeric 37 (representing L24) is pushed back when the carbomethoxy group is held in the same catalytic site. Portions of the enzyme may provide steric hindrance a t this location, accounting for the decreased binding capability of L24 [about twenty times less than that of D24 (75)]. Of the researchers in this field, only Erlanger (80, 81) believes that the phenyl of D24 represents the phenyl of a benzoyl group. Hein and Niemann have criticized his view ( 7 9 , saying that it cannot explain why D24 is so much more reactive (4 x 1O3 times) in the enzymatic process than the L isomer, which has approximately the same reactivity as N-benzoyl-Lalanine methyl ester.

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

40 1

(N-Benzoyl-Lalanine methyl ester is in turn about eight times more reactive than is its D enantiomer). The open-chain compounds may not bind to the enzyme in the same manner, however, as does the locked substrate. The conformation around the amido bond of the open-chain compounds, for example, can be trunsoid rather than cisoid (81). In addition, if equatorial 24 is considered to be the reactive conformer for both the D and Lenantiomers, and if the alanine methyl group is attracted to the hydrophobic aromatic binding subsite, then structures 34 and 38 would result. The L enantiomer of N-benzoyl-phenylalanine methyl ester 38 in this representation has approximately the same conformation as equatorial L24. But attraction of the methyl of the D enantiomer to the location occupied by the methyl group of the L enantiomer causes the carbomethoxy group to move from the position it occupies in D24. 0

38

This explanation, however, accounts more realistically for the eightfold difference in reactivity between the optical isomers of N-benzoylalanine methyl ester than it does for the 1000-fold greater activity brought about by cyclization of DN-benzoylalanine methyl ester into 24.If Erlanger’s hypothesis is correct, it indicates that the position of the /3 carbon is very important in determining reactivity. If this hypothesis is not correct, it is necessary to postulate even greater differences between the binding of cyclized and open-chain substrates, as is discussed in the following section.

D. Different Modes of Binding to the Enzyme The locked substrate may bind to the enzyme in a different way from an unrestricted substrate. If the phenyl portion of D 2 4 binds in the aromatic subsite, then its acylamido group cannot bind at the usual acylamido subsite (82). Cohen justifies this proposal from the fact that some cyclized compounds lacking the acylamido group, e.g., Dmethyl-3,4-dihydroisocoumarin-3-carboxylate, 39,are good substrates for the enzyme.

&mocH3 H 39

402

GEORGE L. KENYON AND JUDY A. FEE

In contrast, substitution of oxygen for -NH- in open-chain compounds causes a great decrease in activity. He states that the heterocyclic ring of D24 locks the carbomethoxy group at the active site and thus accomplishes the same amount of restriction as does binding of both the aromatic and acylamido groups of the open-chain analogs ( 8 2 ) . Blow (23) also believes that Kaiser's cyclic sulfur substrates (83) bind abnormally to the enzyme.

E. Size of Locked Substrates When the locked substrate is only an abbreviated version of the larger natural substrate, the conformations of certain portions of the latter remain open to question. It is obvious that the use of 24 and 25 can at best give clues only about the conformation of those portions of the polypeptide substrate near the point of hydrolysis. The location of the benzoyl group of 25 indicates the approximate position of the amino acid residue adjacent to the one undergoing hydrolysis. Locked analog 24 gives even less information. If its phenyl group represents that of phenylalanine, then it is clearly impossible for the acylamido group of a polypeptide chain substrate to be in the same position as that of D24, because this arrangement would place the next amino acid residue of the chain in exactly the same place as the aromatic ring. Also, although the phenyl group of 25 and perhaps that of D24 suggest the plane in which the indole of a tryptophan residue would lie, as in structure 40, the question remains whether the indole is as it is pictured or whether it is turned 180" (79). In conclusion, one must be aware of these limitations on the use of locked substrate analogs. The problems encountered in the study of a-chymotrypsin are perhaps more severe than for most other enzymes, since a-chymotrypsin normally acts on large, polymeric substrates and is relatively nonspecific. The active site of a-chymotrypsin therefore potentially can bind small substrates such as D24 in a variety of ways. Ideally, larger conformationally restricted substrates should give more information about the active site of a-chymotrypsin. However, besides the increased problenis involved in synthesizing these larger substrates, there is the probleni of increased possibility of uncertainty in their conformations.

VI. CONFORMATIONALLY RESTRICTED ACTIVE-SITE-DIRECTED ENZYME INHIBITORS Studies on the mode of action of the penicillins in inhibiting bacterial cell-wall biosynthesis suggest that the members of this class of antibiotics (including the closely related cephalosporins) are conformationally restricted substrate analogs

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

40 3

for peptidoglycan transpeptidase, an enzyme for which the normal substrate is a peptidoglycan strand terminating with the dipeptide residue Dalanyl-Dalanine (84-86). According to the hypothesis presented by Tipper and Strominger (84), penicillin is a potent, essentially irreversible acylating agent of this enzyme not only because the 0-lactam ring is a reactive acylating group, but also because the molecule is locked into a conformation that is tightly bound to the enzyme. Comparison of models indicates that the conformation of penicillin is similar to a strained form of Dalanyl-Dalanine (cf. structures 41 and 42), a form which the substrate may assume at an intermediate point along the reaction pathway (84). Although the mechanism of the reaction catalyzed by peptidoglycan transpeptidase has not been studied in detail, it is known that the terminal Dalanine is cleaved from the substrate and that the adjacent Dalanine residue becomes cross-linked through a peptide bond to an amino group of another peptidoglycan strand (85). The reactive portion of the substrate is then the peptide linkage between these two Dalanine residues. A possible mechanism for this enzymatic process begins with attack by a nucleophilic side-chain group of the enzyme on the carbonyl of this terminal peptide bond to form a tetrahedral intermediate, which then collapses to give free Dalanine and acylated enzyme. In the second stage, the carbonyl is once again attacked, this time by the amino group of another peptidoglycan strand, and the enzyme is regenerated (85). A comparison of the structures of penicillin and Dalanyl-Dalanine (cf. structures 41 and 42) shows that there is a great deal of similarity between the two molecules. Penicillin is essentially an acylated cyclic dipeptide of Lcysteine and Dvaline (84). As such, it contains a peptide bond, that of the 0-lactam ring, that can acylate the enzyme. Labeling studies of the peptidoglycan transpeptidase of Bacillus subtilis indicate that radioactive penicillin reacts with a sulfhydryl group of a cysteine residue of the enzyme (86). 0

R

K 41

42

A further comparison of structures 41 and 42 shows that the main difference between the structures occurs near this same reactive bond. Structure 42 represents the most stable conformation expected of Dalanyl-Dalanine, where the amide is trans substituted and the nitrogen is oriented so that its lone pair of electrons may overlap with the 71 orbitals of the carbonyl group. In

404

GEORGE L. KENYON AND JUDY A. FEE

contrast, the nitrogen of penicillin is forced to be somewhat pyramidal because of its position in the fused ring system. In the various penicillins whose structures have been investigated, this p-lactam nitrogen lies outside (about .4 A in some cases) the plane defined by its carbon substituents (87). The portion of the molecule containing the free carboxyl group is therefore pulled forward in structure 41 relative to the position equivalent to the corresponding carboxyl group of 42. To explain this difference, Tipper and Strominger (84) proposed that the conformation of penicillin is like that of the substrate when the amide bond is being broken and has thus lost some of its partial double-bond character. Lee later elaborated on the hypothesis that penicillin may be an analog of a transition state in the peptidoglycan transpeptidase reaction (88). According to the strain theory of catalysis (89), the enzyme should have a higher affinity for the distorted transition-state conformation than it does for the unstrained, normal substrate conformation. If penicillin is a transition-state analog, it should bind more tightly to the enzyme than does the substrate. Evidence that this binding occurs (88) is that penicillin is effective at a concentration of about 5 x 1 0 - 3 p m ~ l e / min l the presence of a substrate concentration at least 10,000 times as great (about 62 pmoles/ml). Penicillin is not a perfectly rigid analog of the postulated transition state. There is some flexibility in the five-membered ring which allows the carboxyl group to be either pseudoaxial or pseudoequatorial. Similarly, there is flexibility in the corresponding six-membered ring of the cephalosporins (87). The structure of penicillin does, however, indicate the relative positions of the substituents on the a carbon (corresponding to carbon 6 of penicillin: cf. structure 41) of the penultimate Dalanine residue and the approximate locations of the carboxyl group and the a and /3 carbons of the terminal Dalanine residue. The substrate has no atoms corresponding to the gemdimethyl group at position 2, the sulfur, and carbon 5 of penicillin. This portion of penicillin must either fit into a large pocket in the active site or be directed toward the outer surface of the enzyme. Further evidence that this area is unrestricted is that the cephalosporins, which have an even larger ring system, also irreversibly inhibit the enzyme. From their X-ray studies of cephalosporins, Sweet and Dahl (87) concluded that the determining factor in the biological activity of the penicillins and cephalosporins is the pyramidal character of the bridgehead nitrogen. In their studies, the biologically inactive cephalosporins (e.g., A2-cephalosporins) were found to have planar nitrogens, whereas the nitrogens of the active penicillins and A3-cephalosporins were all pyramidal. In fact, Sweet and Dahl believe that the importance of conformation is minimal in determining biological activity since, except for the geometry of the bridgehead nitrogen, the structures of the active and inactive compounds are all similar. Although results based on biological activity cannot necessarily be attributed to inhibition of one enzyme

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

405

(i.e., there may be transport problems, etc.), it is reasonable to say that the lability of the P-lactam is important in the inhibition by these antibiotics. However, the antibiotics must bind to the enzyme before the reactivity of the p-lactam can have an effect, and, as pointed out above, they must bind very well to compete with a 10,000-fold excess of the substrate and still be effective. That is, both the conformation and the reactivity of the P-lactam are important features. Another antibiotic which seems to be a conformationally restricted substrate analog is cycloserine 43 (90-93), which is generally thought to be an analog of a conformation of alanine (85). A comparison of the Dcycloserine and Dalanine structures is shown in 43 and 44. Despite many studies (94, 85) concerning its mode of inhibition of alanine-requiring enzymes, n o simple pattern has emerged. Khomutov, Severin, and co-workers have reported the syntheses of soma substituted cycloserine derivatives which are locked analogs of other amino acids and reported their effects as inhibitors of enzymes which use the corresponding amino acids as substrates (95-98). The relatively newly discovered antibiotic phosphonomycin, 45, has been shown in convincing studies (99) to be an analog of phosphoenolpyruvic acid (cf. structures 45 and 46). Apparently by mimicking the shape of a favored conformation of phosphoenolpyruvate, it binds to the active site of the enzyme phosphoenolpyruvate: uridine 5'-diphospho-N-acetyl-2-amino-2-deoxyglucose 3-0-enolpyruvyl transferase, which, like peptidoglycan transpeptidase, is involved in the biosynthesis of bacterial cell walls. A sulfhydryl group of a cysteine residue at the active site of the enzyme then attacks the epoxide ring carbon, leading to irreversible inhibition (1 00).

43

45

44

46

In our laboratory we have been investigating the mechanism of action of mandelic acid racemase from Pseudomonas putida (1 Ol), which catalyzes the racemization of either D or Lmandelic acid, 47. Evidence from kinetic and isotopic exchange studies indicates that the racemization proceeds via an

406

GEORGE L. KENYON AND JUDY A. FEE

enzyme-bound carbanion intermediate, 48 (1 02). Recently, we have found in preliminary experiments (103) that the enzyme is inhibited rapidly and irreversibly by low concentrations of D,La-phenylglycidic acid (the D enantiomer is shown in structure 49). D,Lmandelic acid protects the enzyme against the inhibition. The Q carbon of mandelic acid is sp3 hybridized. The corresponding carbons of both a-phenylglycidic acid, 49, and the carbanion intermediate 48 are neither sp3 hybridized nor sp2 hybridized, but presumably between these two extremes. It is therefore possible that the a-phenylglycidic acid is restricted t o a conformation which resembles a transition state in the racemization process, a transition state w h c h would have much of the character of the intermediate 48, and for which the enzyme would presumably have a high affinity (1).

In order to give useful information about an enzyme, a conformationally restricted active-site-directed analog inhibitor need not bind to the enzyme irreversibly. In a study of the enzyme fructose 1,6-diphosphatase from rabbit liver, Benkovic et aZ., have investigated the question of the reactive form of the fructose 1,6-diphosphate in the enzymatic process (104, 105). Three likely forms are shown in structures 50. 5 1 and 52. CH,OPO,'z-0,PO-CH2

-

0

~ 0 ~ , , , , 1 3 c 2--

I

c=o I

HO-C-H H-C-OH I

I

HO

H-?-OH dH,OPO/51

50 (P anomer)

HO

'

52 (r anomer)

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

407

Several analogs locked into the furanose forms but retaining the 1,6-diphosphate groups were prepared:

R, HO

53, R , = CHZOP0,’- R, = OCH, 54, R l = CH,OPO,’-: R, = H 55, R 1 = OCH, , R2 = CH,OPO,’56, R , = H, R, = CH,OPO,’-

Each of these compounds, 53-56, was shown to be a very effective competitive inhibitor of the enzyme with respect t o the fructose 1,6-diphosphate, whereas several other analogs, including acyclic structures, had n o effect. These and other results suggest that the furanose form of the sugar diphosphate is the active form in the enzymatic reaction (1 05). More recent studies using rapid quenchmg techniques and 13C-nmr measurements have confirmed this hypothesis and indicate that the enzyme uses the a! anorner 52 much more rapidly than the 0 anomer 50 and probably uses the a! anomer exclusively (106).

VII. CONCLUSIONS Conforrnationally restricted analogs of substrates can be useful in elucidating both the substrate specificities and the product specificities of enzymes. The restriction can help stabilize an intermediate in the enzymatic process so that it may be isolated. Two or more otherwise structurally equivalent portions of a substrate may be rendered nonequivalent by the restriction so that potential differentiation of these portions by the enzyme in determining product specificity may be investigated. In other cases, new asymmetric centers may be built into the substrate so that the stereochemical course of the overall reaction may be elucidated. The preferred conformation of the natural substrate when bound to the enzyme may be deduced and regions in the space around the enzyme-bound substrate where substituents can be tolerated may be inferred. Acknowledgments We wish t o thank the National Institute of Arthritis and Metabolic Diseases, Grant AM-13529, for financial support. We also wish to thank Drs. Alexander Hampton, Stephen Benkovic, Richard Wolfenden, and Fred Kahan for informing us about their work prior to publication. References 1. Wolfenden, R. W., Acc. Chem. Rex, 5, 10 (1972). 2. Rowley, G. L., A. L. Greenleaf, and G. L. Kenyon, J. Am. Chem. SOC., 93, 5542 (1971).

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GEORGE L. KENYON AND JUDY A. FEE

3. Westley, J., Enzymic Catalysis, Harper & Row, New York, 1969. 4. Mahler, H. R., and E. H. Cordes, Biological Chemistry, Harper & Row, New York, 1966. 5. Cleland, W. W., Biochim. Biophys. Acta, 67, 104 (1963). 6. Cleland, W. W., Biochim. Biophys. Acta, 67, 173 (1963). 7. Cleland, W. W., Biochim. Biophys. Acta, 67, 188 (1963). 8. Cleland, W. W.,Ann. Rev. Biochem., 36, 77 (1967). 9. Cleland, W. W., in The Enzymes, Vol. 11, 3rd ed., P. D. Boyer, Ed., Academic Press: New York, 1970, p. 1. 10. Plowman, K. M., Enzyme Kinetics, McGraw-Hill, New York, 1972. 11. Eigen, M., in Fast Reactions and Primary Processes in Chemical Kinetics, S. Claesson, Ed., Interscience, New York, 1967, p. 333. 12. Hammes, G. G . , and P. R. Schimmel, in The Enzymes, 3rd ed., Vol. 11, P. D. Boyer, Ed., Academic Press, New York, 1970, p. 67. 13. Kustin, K., Ed., Methods in Enzymology, Vol. 16, Academic Press, New York, 1969. 14. Gass, J. D., and A. Meister, Biochemistry, 9, 1380 (1970). 15. Prelog, V., Eidgenossiche Technische Hochschule, Zurich, Switzerland, personal communication. 16. Blow, D. M., and T. A. Steitz, Ann. Rev. Biochem., 39, 6 3 (1970). 17. Doscher, M., and F. M. Richards, J. Biol. Chem., 238, 2399 (1963). 18. Quiocho, F. A,, and F. M. Richards, Biochemistry, 5, 4062 (1966). 19. Butler, L. G., and J. A. Rupley, J. Biol. Chem., 242, 1077 (1967). 20. Birktoft, J. J., D. M. Blow, R. Henderson, and T. A. Steitz, Phil. Trans. R o y . SOC. London, B, 257, 67 (1970). 21. Blake, C. C. F., L. N. Johnson, G. A. Mair A. C. T. North, D. C. Phillips, and V. R. Sarma, Proc. R o y . Soc. London, B, 167, 378 (1967). 22. Steitz, T. A,, R. Henderson, and D. M. Blow, J. Mol. Biol., 46, 337 (1969). 23. Blow, D. M., in The Enzymes, 3rd ed., Vol. 111, P. D. Boyer, Ed., Academic Presq, New York, 1971, p. 185. 24. Leach, S. J., Ed., Physical Principles and Techniques of Protein Chemistry, Academic Press, New York, 1969. 25. McDonald, C . C. and W. D. Phillips, in Biological Macromolecules, Vol. 111, S . N. Timasheff and G. Fasman, Ed., Marcel Dekker, Inc., 1969. 26. Meadows, D. H., 0. Jardetzky, R. M. Epand, H. H. Rutejans, and H. A. Scheraga,Proc. Natl. Acad. Sci., U.S., 60, 166 (1968). 27. Roberts, G . C. K., E. A. Dennis, D. H. Meadows, J. Cohen, and 0. Jardetzky, Proc. Natl. Acad. Sci., U.S., 62, 1151 (1969). 28. Jardetzky, O., and N. G. Wade-Jardetzky, Ann. Rev. Biochem., 40, 605 (1971). 29. Cohn, M., and J. Reuben, Ace. Chem. Rex, 4, 214 (1971). 30. Hamilton, C. L., and H. M. McConnell, in Structural Chemistry and Molecular Biology, A. Rich and N. Davidson, Eds., W. H. Freeman, San Francisco, 1968, p. 115. 31. Hein, G. E., R. B. McGriff, and C . Niemann, J. A m . Chem. Soc., 82, 1830 (1960). 32. Belleau, B., and R. Chevalier, J. A m . Chem. SOC.,90, 6864 (1968). 33. Haeschemeyer, A. E. V., and A. Rich, J. Mol. Biol., 27, 369 (1967). 34. Sasisekharan, V., A. V. Lakshminarayanan, and G. N. Ramachandran, in Conformation of Biopolymers, Vol. 11, G. N. Ramachandran, Ed., Academic Press Inc., New York, 1967, p. 641. 35. Kraut, J., and L. H. Jensen,Acta Cryst., 16, 79 (1963). 36. Sundralingam, M., Acta Cryst., 21, 495 (1966). 37. Watenpaugh, K., J. Dow, L. H. Jensen, and S . Furberg, Science, 159, 206 (1968). 38. Haeschemeyer, A. E. V., and H. M. Sobell,Nature, 202, 969 (1964).

CONFORMATIONALLY RESTRICTED SUBSTRATE ANALOGS

409

39. Haeschemeyer, A. E. V., and H. M. Sobell, Acta Cryst., 19, 125 (1965). 40. Schweizer, M. P., A. D. Broom, P. 0. P. Ts’o, and D. P. Hollis, J. A m . Chem. Soc., 90, 1042 (1968). 41. Alderfer, J. L., and S. L. Smith, J. Am. Chem. Soc., 93, 7305 (1971). 42. Saenger, W., and K.-H. Scheit, Angw. Chem. Intern. Ed. Engl., 8, 139 (1969). 43. Tavale, S. S., and H. M. Sobell, J. Mol. Biol., 48, 109 (1970). 44. Kapuler, A. M., Ph.D. Thesis, Rockefeller University, New York, 1969. 45. Harper, P. J., and A. Hampton, J. Org. Chem., 37, 795 (1972). 46. Hampton, A,, The Institute for Cancer Research, Philadelphia, Pennsylvania, personal communication. 41. Ikehara, M., Ace. Chem. Rex, 2, 47 (1969). 48. Ikehara, M., and H. Tada, Chem. Phatm. Bull., Tokyo, 15, 94 (1967). 49. Ogilvie, K. K., L. Slotin, and P. Rheault, Biochem. Biophys. Res. Comm., 45, 297 (1971). 50. Simon, L. N., R. J. Bauer, R. L. Tolman, and R. K. Robins, Biochemistry, 9, 573 (1970). 51. Ikehara, M., I. Tazawa, and T. Fukui, Biochemistry, 8, 736 (1969). 52. Kapuler, A. M., C. Monny, and A. M. Michelson, Biochim. Biophys. Acta, 217, 18 (1970). 53. Kapuler, A. M., and E. Reich, Biochemistry, 10, 4050 (1971). 54. Cramer, F., E. M. Gottschalk, H. Matzura, and K.-H. Scheit, Eur. J. Biochem., 19, 379 (1971). 55. Lipsett, M. N., J. Biol. Chem., 240, 3975 (1965). 56. Scheit, K.-H., Angew. Chem. Intern. Ed. Engl., 6, 180 (1967). 57. Eckstein, F., FEES (Fed. Eur. Biochem. Soc.) Letters, 2, 85 (1968). 58. Usher, D. A,, D. I. Richardson, Jr., and D. G. Oakenfull, J. Am. Chem. Soc., 92, 4699 (1970). 59. Saenger, W., and F. Eckstein, J. Am. Chem. Soc., 92, 4712 (1970). 60. Eckstein, F., W. Saenger, and D. Suck, Biochem. Biophys. Res. Comm., 46, 964 (19 72). 61. Usher, D. A., D. I. Richardson, Jr., and F. Eckstein, Nature, 228, 663 (1970). 62. Westheimer, F. H., Ace. Chem. Res., I , 70 (1968). 63. Eckstein, F., and H. Gindl, Chem. Ber., 101, 1670 (1968). 64. Meister, A., Adv. Enzymology, 31, 182 (1968). 65. Gass, J. D., and A. Meister; Biochemistry, 9, 842 (1970). 66. Tsuda, Y., R. A. Stephani, and A. Meister, Biochemistry, 10, 3186 (1971). 67. Krishnaswamy, P., V. Pamiljans, and A. Meister, J. Biol. Chem., 237, 2932 (1962). 68. Morrison, J. F., and E. James,Biochem. J., 97, 37 (1965). 69. Morrison, J. F., and W. W. CIeland,J. BiolChem., 241, 673 (1966). 70. Morrison, J. F., and A. White, Eur. J. Biochem., 3, 145 (1967). 71. McLaughlin, A. C., M. Cohn, and G. L. Kenyon, J. Biol. Chem., 247, 4382 (1972). 72. Struve, G., and G. L. Kenyon, unpublished results. 73. Hein, G. E., and C. Niemann, J. Am. Chem. Soc., 84, 4495 (1962). 74. Cohen, S. G., and R. M. Schultz, J. Biol. Chem., 243, 2607 (1968). 75. Hein, G. E., and C. Niemann, J. Am. Chem. Soc., 84, 4487 (1962). 76. Silver, M. S., and T. Sone, J. A m . Chem. Soc., 90, 6193 (1968). 77. Awad, E. S., H. Neurath, and B. S. Hartley, J. Biol. Chem., 235, PC 35 (1960). 78. Lawson, W. B., J. Biol. Chm., 242, 3391 (1967). 79. Hayashi, Y., and W. B. Lawson, J. B i d . Chem., 244, 4158 (1969). 80. Wilson, I. B., and B. F. Erlanger, J. A m . Chem. Soc., 82, 6422 (1960). 81. Erlanger, B. F., Proc. Natl. Acad. Sci.. U.S., 58, 703 (1967).

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Cohen, S. G., and L. W. Lo, J. Biol. Chem., 245, 5718 (1970). Kaiser, E. T.,Acc. Chem. Res., 3, 145 (1970). Tipper, D. J., and J . L. Strominger,Proc. Natl. Acad. Sci., U.S., 54, 1133 (1965). Strominger, J. L., K. Izaki, M. Matsuhashi, and D. J. Tipper, Fed. Proc., 26, 9 (1967). Lawrence, P. J., and J. L. Strominger, J. Biol. Chem., 245, 3653 (1970). Sweet, R. M., and L. F. Dahl, J. Am. Chem. Soc., 92, 5489 (1970). Lee, B., J. Mol. Biol,, 61, 463 (1971). Jencks, W.P., Catalysis in Chemistry and Enzymology, McGraw-Hill, New York, 1969, p. 294. 90. Kuehl, F. A., Jr., F. J . Wolf, N. R. Trenner, R. L. Peck, R. P. Buhs, I. Putter, R. Orrnond, J. E. Lyons, L. Chaiet, E. Howe, B. D. Hunnewell, G. Downing, E. Newstedd, and K. Folkers, J. Am. Chem. SOC., 77, 2344 (1955). 91. Hidy, P. H., E. B. Hodge, V. V. Young, R. L. Harned, G. A. Brewer, W. F. Phillips, W. F. Runge, H. E. Stavely, A. Pohland, H. Boaz, and H. R. Sullivan,J. Am. Chem. SOC., 77, 2345 (1955). 92. Strominger, J. L., E. Oto, and R. H. Threnn, J. Am. Chem. Soc., 82, 998 (1960). 93. Neuhaus, F. C., and J. L. Lynch,Biochemistry, 3, 471 (1964). 94. Khomutov, R. M., E. S. Severin, G. K. Kovdleva, N. N. Gulyaev, N. V. Gnuchev, and L. P. Sastchenko, in Pyridoxal Catalysis: Enzymes and Model Systems, E. E. Snell, A. E. Braunstein, E. S. Severin, and Yu. M. Torchinsky, Eds., Interscience, New York, 1968, p. 631. 95. Khomutov, R. M., G. K. Kovaleva, E. S. Severin, and L. V. Vdovina, Biokhimiya, 32, 900 (1967). 96. Severin, E. S., N. V. Gnuchev, H. K. Kovaleva, N. N. Gulyaev, and R. M. Khomutov, Pyridoxal Catalysis: Enzymes and Model Systems, E. E. Snell, A. E. Braunstein, E. S. Severin, and Yu. M. Torchinsky, Eds., Interscience, New York 1968, p. 651. 97. Severin, E. S. N. N. Guyaev, and R. M. Khomutov, Biokhimiya, 34, 66 (1969). 98. Sastchenko, L. P., E. S. Severin, D. E. Metzler, and R. M. Khomutov, Biochemistry, 10,4888 (1971). 99. Hendlin, D., E. 0. Staeley, and H. B. Woodroff, Science, 166, 112 (1969). 100. Kahan, F., and J. Kahan, manuscript in preparation. 101. Hegeman, G. D., E Y. Rosenberg, and G. L. Kenyon, Biochemistry, 9,4029 (1970). 102. Kenyon, G. L., and G. D. Hegeman, Biochemistry, 9, 4036 (1970). 103. Fee, J. A,, G. D. Hegeman, and G. L. Kenyon, unpublished results. 104. Benkovic, S. J., M. M. de Maine, and J . J. Kleinschuster, Arch. Biochem. Bioplzys., 139, 248 (1970). 105. Benkovic, S. J . , J. J. Kleinschuster, M. M. de Maine, and I. J. Sewers, Biochemistry, 10, 4881 (1971). 106. Schray, K. J., S. J. Benkovic, P. A. Benkovic, I. A. Rose, and A. S. Mildvan, unpublished results. 82. 83. 84. 85. 86. 87. 88. 89.

The Enthalpy-Entropy Relationship By Otto Exner Institute of Organic Chemistry and Biochemistry. Czechoslovak Academy of' Sciences. Prague. Czechoslovakia

CONTENTS

I . Introduction . . . . . . . . . . . . . . . . I1 . Historical . . . . . . . . . . . . . . . . 111. Definition and Significance . . . . . . . . . . . IV. Statistical Treatment . . . . . . . . . . . . . A . General Problems . . . . . . . . . . . . . B . Kinetic Measurements at Two Temperatures . . . . . C. Kinetic Measurements at Several Corresponding Temperatures D . Kinetic Measurements at Arbitrary Temperatures . . . . E . Calorimetric and Equilibrium Measurements . . . . . V . Theoretical Corollaries . . . . . . . . . . . . . A . The Isokinetic Temperature . . . . . . . . . . B . Classification of Reaction Series . . . . . . . . . C . Derivation and Generality of the Isokinetic Relationship . . D . Relation to Extrathermodynamic Relationships . . . . VI . Significance of AG. AH and AS in Structural Chemistry . . . VII . More General Relations . . . . . . . . . . . . A . Temperature-Variable Activation Parameters . . . . . B . Relationships between Arbitrary Quantities . . . . . . VIII . Concluding Remarks . . . . . . . . . . . . . IX . Appendix . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . .

. . . . 413

. . . .

417

. . . . . . . .

428 428 434 440 448 453 456 456 458 460 463 466 410 470 472 473 476 476

. . . . 419

. . . .

. . . .

. . . . . . . .

. . . .

. . . .

. . . . . . . .

. . . .

. . . . . . . .

LIST OF SYMBOLS empirical coefficients preexponential factor arbitrary constants proportionality constant in eq . (14) regression coefficients (subscripts denote the variables) regression coefficients transformed into new variables slopes of the Arrhenius lines (isokinetic. unconstrained. const rained) 41 1

412

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symbol for heat capacity of activation or reaction random variable (error) intercept in eq. (1 1a) Arrhenius activation energy potential energy zero-point energy degrees of freedom partition functions of the final, ground, and transition states, respectively symbol for activation or reaction free enthalpy reaction free enthalpy activation free enthalpy intercept in eq. (1 1 ) symbol for reaction or activation enthalpy reaction enthalpy activation enthalpy isokinetic (reaction or activation) enthalpy external and internal parts of AH subscript denoting the pertinent straight line (i.e., reaction) subscript denoting the pertinent point (i.e., temperature) symbol for rate or equilibrium constant (temperature and reaction given by subscripts) number of straight lines (i.e., reactions) auxiliary symbols defined by eq. (46) number of points on a line (i.e., temperatures) number of measurements function of variables defined by eq. (35) auxiliary symbols defined by eq. (44) correlation coefficients (subscripts give the correlated quantities) mean square deviations of the pertinent quantities from their averages standard deviation from the regression line standard deviations (isokinetic, unconstrained, constrained) from the system of lines residual sums of squares (isokinetic, unconstrained, constrained) symbol for reaction or activation entropy reaction entropy activation entropy isokinetic (reaction or activation) entropy external and internal parts of AS

THE ENTHALPY -ENTROPY RELATIONSHIP

TlT2 Tj U UO

UXYZ Wij

Xijxj X

Xi.

XO YijYi 1 Yi2

Yi.Y ..Y. 1 Y. 2 YOYU

a P P1P2 Pext PT

Y YT

6

413

temperatures independent variable introduced by eqs. (36), (36a) auxiliary symbols defined by eq. (44) weights of measurement independent variable (= T-’) average values of x abscissa of the isokinetic point (= ,T1) dependent variable (= log k) average values of y ordinate of the isokinetic point confidence level isokinetic temperature temperature dependent “isokinetic temperature” reciprocal isokinetic temperature (symbol not recommended) proportionality constant in eq. (81) operator denoting the difference between two reactions experimental error of the pertinent quantities operator denoting the difference between the final (transition) and ground state reaction constant in extrathermodynamic equations substituent constant in extrathermodynamic equations variance of eij broadness of the temperature interval, defined by eq. (45) inclination of a special regression line, eq. (33) statistical distribution function independent variable structure parameter

I. INTRODUCTION The problem of relationship between the activation parameters-the so called isokinetic relationship or compensation law-is of fundamental importance in structural chemistry, organic or inorganic. However, there are few topics in which so many misunderstandings and controversies have arisen as in connection with this problem. A critical review thus seems appropriate at present, in order to help in clarifying ideas and to draw attention to this treatment of kinetic or equilibrium data. The subject has already been reviewed (1-6), but sufficient attention has not been given to the statistical treatment which represents the heaviest problems. In this review, the statistical problems are given the first place. Theoretical corollaries are also dealt with, but no attempt was made to collect all examples from the literature. It is hoped that most of the important

OTTO EXNER

414

references up to 1970 are included. The point of view is essentially that of an organic chemist, but many references are made from other fields of chemistry. There is no doubt that one of the main tasks of chemistry is to interpret and predict reactivity, but there is no general agreement as to which physicochemical quantity should serve as its measure. Most frequently and most simply, the reactivity is expressed by the values of equilibrium constants, K, or rate constants, k; however, both of these quantities are strongly dependent on temperature. Hence, the relative reactivity can be reversed when temperature is changed (7, 8), and most theories of structural chemistry in which the temperature dependence is not incorporated, e.g., inductive and mesomeric substituent effects, ring strain, steric hindrance, etc., may fail. This effect is particularly striking (2, 3 , 9 ) when the reactivity in a given reaction series is controlled by a kind of extrathermodynamic relationship (LFER): i.e., when reactivity is quantitatively related to another series or to a fixed scale of constants. Promising progress seemed to be achieved by dividing the reactivity into temperature dependent (enthalpic) and temperature independent (entropic) parts. Their separation is unambiguous in the case of equilibrium constants, because the equation

K

= e-

AHOIRT

e ~ /R sa

(1 1

defines the standard reaction enthalpy, AH', arid the standard reaction entropy, ASo. In kinetics, either the classical but still sufficient (10) Arrhenius theory may be applied, k=Ae

(2)

E'IRT

using the (Arrhenius) activation energy, E*, and the preexponential factor, A, or use is made of activated complex theory,

which yields an activation enthalpy, A H S , and an activation entropy, ASs. In practice, both theories are of comparable value and are being used alternatively in the literature, because an experimental decision between them is practically impossible. In the former, a plot (or statistical regression) of log k against T-', in the latter of log (k/T) against T-', is made, and the attainable accuracy does not allow one to decide which is more exactly linear. Often the former, simpler plot is preferred, and from the primarily determined E* and log A, the values of AH$ and A S * are calculated subsequently according t o the equations

AH$ = E*-RT AS* = 2.303 R (log A -log T

(4) ~

10.75)

(5)

THE ENTHALPY-ENTROPY RELATIONSHIP

415

(Equation (5) holds for rate constants of the first order in sec-* and of the second order in 1 mol-' sec-'.) Therefore, no distinction will be made between the two pairs of the activation parameters in this paper: the computation usually will be carried out in the simpler terms of Arrhenius theory, but all of the results will apply equally well for the activation enthalpy and activation entropy, too. Furthermore, many considerations apply to equilibria as well as to kinetics: then the symbols AH, AS, AG will mean AH*, AS*, AGS as well as AH', ASo, AGO, and k will denote either rate or equilibrium constant. The activation parameters are much less sensitive to temperature changes than are rate or equilibrium constants and usually can be taken as being practically invariant in a narrow temperature interval. The considerations of this paper will be essentiaily confined to this first approximation with constant AH and AS. (For exceptions, see Section V1I.A.). By division of the reactivity into the enthalpic and entropic parts, the possibility is offered of discussing each separately (10, 11). Entropy values have been particularly used for mechanistic conclusions (1 1) when only their order of magnitude is considered. On the other hand, discussions of minute differences inside a reaction series in terms of AH and AS have generally met with less success. Usually, polar substituent effects and steric effects that result from strain and repulsion in a rigid molecule have been connected with AH, and solvent effects and the kinetic part of steric effects with AS (12-15). However, it was proved already by Hammett (16) that these parameters in fact have only limited fundamental validity compared to the original free energy quantities (i.e., k or K). The proper quantity to be correlated with structure in classical terms as expressed by a static model is only the experimentally inaccessible potential energy, AEp. The standard free energy change, AGO, can be divided into the potential AEp, zero-point AEz, and kinetic energy terms, the last being expressed by partition functions f G and f F of the ground state and final state, respectively (1 6): AGO

= AEp t

AEz + RT In -

c>

(6)

):(

(7)

Similarly, AHo can be expressed: AHO

=AEptAEZ-RT2

-

ddT

In

--

Quite similar equations can be formulated for AG* and AHS by use of the partition function f S of the activated complex. It follows from equations (6) and (7) that AEp can only be evaluated if the partition functions and AEz are available from spectroscopic data or heat capacity measurements. However, if AG = AH, the entropy change AS equals zero, and if AEz is also equal to zero, either AG or AH can then be identified with the potential energy change. If

416

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only various effects on reactivity within a reaction series are coixerned, it is sufficient that the entropy change be constant; this condition reads*

& A S= 0 In this case, the following equality holds: 6AG = 6AH = 6AEp and either 6AG or 6AH can be used in discussion of substituent or solvent effects, or, generally, of relative reactivity within a given series. Therefore, reaction series with constant entropy have been accorded great significance and have been investigated thoroughly. The condition in eq. (8) was even considered necessary for any linear free energy relationship to hold (16). However, as experimental data accumulated and precision improved, it was clear that for many theoretically important reaction series, this condition is not fulfilled (1, 17). It was also proved that a LFER can hold if entropy is not constant, but linearly related to enthalpy (18, 19). The linear equation

6AH = p 6AS or 6E* = 2.303 Rp 61og A is usually called the isokinetic relationship (l), although it can be concerned with equilibria, too. The term isoequilibrium relationship is seldom used. The alternative term, compensation effect (4) or compensation law, is based on the supposition that the proportionality constant is positive so that AH and AS change in the same direction and the resulting variations of AG are less than they would be when controlled by either A H or AS alone. This assumption will be discussed in Section V.B. The proportionality constant 0 is called the isokinetic temperature, and its possible values and physical meaning will be discussed in Section V.A. Equation (10) was derived from the relationship to LFER’s, and in this respect, it is of the same significance as the condition of eq. (8). However, there is the distinction between both that eq. (10) itself offers no possibility of obtaining the potential energies 6AEp. It is assumed, but not proved, that in this case, too, 6AEp is proportional to 6AG (1). At any rate, the validity of eq. (10) solves the problem of whether A G or A H should be used for structural discussions, since the two quantities are now equivalent. In general, it cannot be decided which of both experimental quantities, AH and AG, is a better approximation for the unknown potential energy, AEp. Nevertheless, some

* The operator 6 will denote the difference between an arbitrary and a standard reaction (2): i.e., the effect of substitution, solvent, etc. It is to be distinguished from A , which refers to the difference between the ground and final (transition) states.

THE ENTHALPY-ENTROPY RELATIONSHIP

411

theoretical arguments have been given in favor of the free energy (20,21) (i.e., the rate or equilibrium constant), and this quantity is preferred in most (22) but not all (7, 12) discussions of structure and reactivity. We shall return to this question in Section VI. 11. HISTORICAL

Qualitative and quantitative relations between enthalpy and entropy were observed several times in the 1920’s, and their importance was rightly recognized by some authors. However, some ideas from this early work seem to have been overlooked later, perhaps because they were connected with obsolete theories or because they were developed independently in the fields of organic chemistry, catalysis, and pure physical chemistry. For this reason, a brief historical survey seems appropriate. The first observations of the phenomenon seem to have been made by Constable (23), Grimm and Schwamberger (24), Cremer (25) and Gapon (26), and the first theoretical treatments were made by Constable (23), Cremer and Schwab (27,28), Roginsky and Rosenkewitsch (29), Syrkin (30), Evans and Polanyi (20), Fairclough and Hinshelwood (31), and Christiansen (32). In the work of Schwab (28), the problem was already presented in its present conception, while Gapon (26) first formulated all pertinent relations and graphs and viewed them as a general natural law. His work, hidden in an unfamiliar journal, seems to have been overlooked by later authors. Graphs of E* against log k were also often used, mainly by Hinshelwood; the purpose originally was to prove only that the entropy is constant (33-35). Sometimes forms deviating from simple linear relations were used in this early work, particularly the relation of log A to E-” (31, 36), which was derived theoretically (29) but later rejected (37, 38). Otherwise, the quantity log (kM”) was plotted instead of log k, M-’being the sum of reciprocal masses of reacting particles according to collision theory (33), and this correction was also later abandoned (34). The two modifications mentioned, in practice, have little influence on the shape of the graph, and the simple plot of E* versus log A (or AH versus AS) is now preferred. The variable factor in reaction series usually was a substituent change, although solvent variation also has been given special attention (39-44). Variations of catalyst (4, 5, 23-25, 45-49), ionic strength (50), or pressure (51, 52) also have been studied. In exceptional cases, temperature can become the variable parameter if the kinetics has been followed over a broad temperature range and the activation parameters are treated as variable (53), or temperature as well as structural parameters can be changed ( 6 ) . Most of the work done concerns kinetics, but isoequilibrium relationships also have been observed (2, 54-58), particularly with ionization equilibria (59-82).

418

OTTO EXNER

In addition to chemical reactions, the isokinetic relationship can be applied to various physical processes accompanied by enthalpy change. Correlations of this kind were found between enthalpies and entropies of solution (20, 83-92), vaporization (86, 91), sublimation (93, 94), desorption ( 9 9 , and diffusion (96, 97) and between the two parameters characterizing the temperature dependence of thermochromic transitions (98). A kind of isokinetic relationship was claimed even for enthalpy and entropy of pure substances when relative values referred to those at 298” K are used (99). Enthalpies and entropies of intermolecular interaction were correlated for solutions, pure liquids, and crystals (6). Quite generally, for any temperature-dependent physical quantity, the “activation parameters” can be computed in a formal way, and correlations between them have been observed for dielectric absorption (1 00) and resistance of semiconductors (101-105) or fluidity (40, 106). On the other hand, the isokinetic relationship seems to hold in reactions of widely different kinds, starting from elementary processes in the gas phase (107) and including recombination reactions in the solid phase (108), polymerization reactions (109), and inorganic complex formation (1 10-1 I2), up to such biochemical reactions as denaturation of proteins (1 13) and even such biological processes as hemolysis of erythrocytes (1 14). Recent development originates in the paper of Leffler ( l ) , who recognized the generality of the isokinetic phenomenon and collected and discussed some 80 examples in organic chemistry. Simultaneously with Gilkerson and Gallup (1 8), Leffler deduced the connection to extrathermodynamic relationships (1 9). Further examples and discussions of the significance and validity range have been given by Blackadder and Hinshelwood (1 15, 116), Beltrame and Simonetta (1 17), Brown ( I 18, 119), and Leffler and Grunwald (2) in the field of organic chemistry and by Cremer (4) and Bond (5) in the field of heterogeneous catalysis. Theoretically, the problem has been attacked by various approaches and on different levels. Simple derivations are connected with the theory of extrathermodynamic relationships and consider a single and simple mechanism of interaction to be a sufficient condition (2, 120). Alternative simple derivations depend on a plurality of mechanisms (4, 121, 122) or a complex mechanism of so called cooperative processes (1 13), or a particular form of temperature dependence (123). Fundamental studies in the framework of statistical mechanics have been done by Riietschi (96), Ritchie and Sager (124), and Thorn (125). Theories of more limited range of application have been advanced for heterogeneous catalysis (4, 5, 46-48, 122) and for solution enthalpies and entropies (126). However, most theories are concerned with reactions in the condensed phase (6, 127) and assume the controlling factors to be solvent effects (13, 21, 56, 109, 116, 128-130), hydrogen bonding (131), steric (13, 116, 132) and electrostatic (37, 133) effects, and the tunnel effect (4,

THE ENTHALPY-ENTROPY RELATIONSHIP

419

102). Solvent effects also play an important role in the theory separating enthalpy and entropy into external and internal parts (134-136) or, in other terms, into reaction and hydration contributions (79). This treatment has been widely used (71, 73, 78, 137-141). The most general thermodynamic treatment of intermolecular interaction was given by Rudakov (6) for various states of matter and for solution enthalpy and entropy as well as for kinetics. A particular case is hydrophobic interaction (6,89,90). Several doubts about the correctness of the usual statistical treatment were expressed already in the older literature (31), and later, attention was called to large experimental errors (142) in A H and AS and their mutual dependence (143-145). The possibility of an apparent correlation due only to experimental error also was recognized and discussed (1, 2, 4, 6, 115, 116, 119, 146). However, the full danger of an improper statistical treatment was shown only by this reviewer (147) and by Petersen (148). The first correct statistical treatment of a special case followed (149) and provoked a brisk discussion in which Malawski (150, 151), Leffler (152, 153), Palm (3, 154, 155) and others (1 56-161) took part. Recently, the necessary formulas for a statistical treatment in common cases have been derived (162-164). The heart of the problem lies not in experimental errors, but in the a priori dependence of the correlated quantities, A H and AS. It is to be stressed in advance that in most cases, the correct statistical treatment has not invalidated the existence of an approximate isokinetic relationship: however, the slopes and especially the correlation coefficients reported previously are almost always wrong. Generalization of the isokinetic relationship was attempted in several directions. The fundamental equation was completed with an additional term accounting for potential-energy changes (165-167), and in this way a direct connection to extrathermodynamic relationships was achieved. On the other hand, empirical relations between thermodynamic quantities other than A H and AS were sought (168, 169). The utmost generalization consists of replacing the two primary variables-temperature and reaction-with another couple of variables. These may be two substituent parameters (1 70) or, quite generally, two arbitrary parameters whereby the so called isoparametric relationship is produced (171).

111. DEFINITION AND SIGNIFICANCE

Equation (10) represents the simplest form of the isokinetic relationship: however, several equivalent expressions are also possible and will now be discussed and shown in diagrams. It should be commented in advance that algebraic equivalence does not imply equivalence from the statistical point of view (see Section IV.).

420

#en the form

OTTO EXNER

the operator 6 is not applied in eq. (lo), the latter can be written in

AH = ho +PAS or

E* = eo t 2.303 R/3 log A

(1 1 )

(1 la)

This formulation is of advantage only when the constant ho (eo) is given a physical meaning (1 18, 119) or a supposed general linear relation between ho and 0-the so called hypercompensation effect (6)-is looked for (26, 102) or when it can be shown that ho is equal to zero (30,45, 172). Usually, or at least in kinetics, ho and e, are simply seen as intercepts without any special meaning and without a general relationship to /3. Of course, eq. (1 1) can be written with interchanged variables, and in this case the intercept so can be interpreted as the so called model entropy (6).

AH' htl

I-

7-

s-

5-

4-

3-

Figure 1. Example of the isokinetic relationship in the coordinates AH versus AS; isoequilibrium relationship in the ionization of anilinium ions (69, 7 1).

THE ENTHALI'Y-ENTROPY RELATIONSHIP

42 1

Instead of p , its reciprocal value, denoted y, is used sometimes (3, 124, 156) in eqs. (10) and (11): however, the symbol y can also stand for 1/(2.303 Rp) (154, 155). For this reason, it will not be used in this paper. Alternatively, these equations can be modified by taking TAS as a variable, and the proportionality constant is then b/T and is called the compensation factor (173). As an example of the graphical representation of the isokinetic relationship in the coordinates AH and AS, see Figure 1, ionization of meta- and para-substituted anilinium ions in water. This example is based on recent exact measurements (69, 71) and clearly shows deviations that exceed experimental error, but the overall linear correlation cannot be doubted. From the relation between AH and AS, the relation between AG and AS follows immediately. Of course, log k can be plotted directly instead of AG:

01

S log A =

T 6 log k T-P

This relation has also been used from time to time [see (6, 62, 74-77, 174-176)] . An example is given in Figure 2 for the same reaction series as in Figure 1. The

I 1

I 2

I

I

3

4

I 5

I

I

6

I

I

*

I AGbI

Figure 2. Example of the isokinetic relationship in the coordinates A S versus A G (the same reaction series as in Figure 1).

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422

third possible combination of variables, AG with AH, leads to the equation

or

6E* = 2'303 RTP 6 logk T-P

(134

The corresponding plot is shown in Figure 3 . This type of plotting has been used extensively [e.g., (26, 115, 116)], formerly often with the idea only to test whether the entropy is constant (34, 35, 38, 177, 178). In this case, the slope equals 1 or -2.303 RT in eqs. (13) and (13a), respectively. The three eqs. (lo), (12), and (13) are strictly equivalent from the points of view of algebra and physical chemistry but not from that of statistics: that is, the correlation need not be equally close in all plots (176). The correlation in Figure 3 is apparently much better than that in the first two; this results from the fact that variations of enthalpy are about four times larger than variations of TAS, and changes of AG are controlled mainly by AH. The question arises as to which kind of plotting is the best one: i.e., which gives the true picture of the correlation and its scatter. If two of the quantities are obtained independently, their mutual plot is statistically unobjectionable; this can happen in practice when A H is determined calorimetrically and AG is determined from the equilibrium. When all quantities

I

I

I

I

I

I

I

1

2

3

4

5

s

7

AGW

Figure 3. Example of the isokinetic relationship in the coordinates A H versus A G (the same reaction series as in Figures 1 and 2).

THE ENTHALPY-ENTROPY RELATIONSHIP

423

are obtained from the same set of measurements, for example, from the temperature dependence of rate or equilibiium constants, no one of the three plots is statistically correct. Another expression for the isokinetic relationship relates two rate or equilibrium constants (kl, k,) measured at two temperatures (T2 > TJ* The linear relationship holds logk2 = a t b l o g k l where the slope b is related to /Iby the equation

Remarkably enough, this simple kind of plotting was omitted by early authors. Palm and Vizgert found an example where it gives a good correlation even though the plot AH versus AS does not, and they attributed this feature to the great sensitivity of AH and AS to experimental errors (179). Subsequently, eq. (14) was derived by Malawski (150) and used by the reviewer (149) to develop the first statistically correct method for testing the isokinetic relationship and computing its slope. From the slope b in the coordinates log k2 versus log k l , the isokmetic temperature fl is readily obtained (149, 150) according to eq. (1 5). The procedure has been applied to many reaction series (57, 58, 91, 97, 154, 155, 157, 180-185). Since the values of log k l and log k2 are determined by independent experiments, this kind of plotting is always statistically correct and the slope b can be determined easily and with relative accuracy (see Section 1V.B.). However, in computation of 0 according to eq. (15), a large error arises if the temperatures T1 and Tz are close together (150, 152, 157). This is not a defect of the method since no other one exists which would allow this value to be obtained more accurately; the amount of information involved in the data is simply insufficient. However, a certain shortcoming can be seen in the fact that an excellent correlation in the graph of log k2 against log k l can simulate the existence of an exact isokinetic relationship and, in fact, may result only from the narrow temperature interval: that is, when T1' T 2 , eq. (14) holds exactly, of course. Compare the three lines in Figure 4, taken from the same reaction series (186, 187) and differing in temperatures: the upper one proves a real but limited isokinetic relationship; the lowest one is no real proof of its validity although the apparent correlation is much better. Furthermore, this kind of plotting is quite natural when the rate constants are measured only at two temperatures. With measurements extended over more different temperatures,

* The original denotation (149) has been reversed to comply with other references (3, 142, 150, 154, 155).

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-1

0

''lk,o

Figure 4. Isokinetic relationship in the coordinates log k, versus log k, with k, at three different temperatures; alkaline decomposition of Malachite-Green-like dyestuffs (186, 187).

either a part of them remains unutilized, or actual experimental values must be replaced by averaged ones (1 88). In addition, a method has been advanced (156) based on the multiple regression log kij = a. t al T;'

+ a2 log k i l t a3TY1 log kil

(16)

where the rate 4, of the ith reaction at the jth temperature is correlated with the given temperature Tj and the rate kil of the same reaction at the standard temperature TI. From the coefficients a2 and a3, the value of 0 is obtained. The method has the shortcoming that this standard temperature is given special significance: thus, all measurements are not weighted equally. In addition, there is a principal defect that statistical estimates are used further to make new estimates. The most general representation of the isokinetic relationship is the plot of log k against the reciprocal temperature. If the Arrhenius law is followed, each

425

THE ENTHALPY-ENTROPY RELATIONSHIP

reaction of the series is given as a straight line, and if in addition the isokinetic relationship holds, all of the lines intersect in one point. It can be shown by a simple algebraic operation that the abscissa of the point of intersection equals the reciprocal isokinetic temperature @ - I ) . An example is shown in Figure 5, taken from a heterogeneous catalysis (1 89). Instead of log k, log (k/T) could also be plotted (190) according to activated complex theory, but the correlation is

I 13

I H

I

I

I

15

Is

1.7

re' M s

Figure 5. isokinetic relationship in the coordinates log k versus T-' ;decomposition of formic acid on various catalysts (189).

The plot log k versus T-' was already used by Schwab (28) and Gapon (26), and later by many others [e.g. (4, 5, 130, 160)]; its fundamental importance was advocated by Petersen (148) and Malawski (151). It is always statistically unobjectionable, since log k and T are a priori independent. However, the determination of 0 is a difficult problem. An estimation from the graph is not dependable if the straight lines do not intersect in one point; statistical methods have been developed only recently (163, 164) and are rather laborious (see Section 1V.C.-D.). However, it is only this method which gives the possibility of estimating the error in and of deciding whether the isokinetic relationship is statistically significant or not. The last method for illustrating an isokinetic relationship is based on the dependence on a parameter. If both AH and AS are related to the parameter 5 , then by its elimination from the two equations, the relation between AH and

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AS can be obtained. In most practical applications, the parameter is the solvent composition (41-44, 192-194): however, the functional relationships are of complicated form and have not been expressed algebraically. A slightly different approach makes use of the relationship between l o g k and the parameter [-usually the substituent constant u-at different temperatures. From the temperature dependence of the slope-the reaction constant p-the value of 0 is then obtained indirectly (3, 155). Consider the generalized Hammett equation (9, 17) in the form 6l o g k = p ~ ~

(1 7)

where u stands for any kind of structural parameter and is temperature independent, while the slope PT is a function of temperature. By combining eq. (17) with either (12a) or (13a), we get this function in the form (19, 195, 196) p ~=. const.

(1 -PIT)

(1 8)

giving 13 as the slope in the plot of p~ against T-I. Alternatively, the many-parameter relationship among log k, T, and [ (usually a kind of constant u) is obtained by least-squares fitting, of which the simplest form is (156) log k

= a.

+ al T-' + a2 [ + a3[T-'

(19)

This equation describes the series of lines in Figure 5 , the variable parameter being represented by [. The physical meaning of coefficients ai follows from comparison of eqs.(17), (18) and (19): a. equals logAo and a l = - E o / 2.303 RT, the subscripts 0 referring to the standard substituent, a2 = p - at the infinite temperature, and a3 = -@pa. Hence, 0 is obtained as -a3/az. Direct correlations of A H and A S with u (176, 197, 198) or other parameters (199, 200) are usually bad and cannot serve to obtain the AH/AS relationship. The whole concept based on parameters, although used several times (3, 57, 155, 156, 201) and advocated particularly by Good and Stone (200), has a principal defect. The results are dependent not only on experimental rate constants, but also on the values of the parameter and on the form of the correlation equation used. Furthermore, the procedure does not give any idea of the possible error. Hence, it could be acceptable only in an unrealistic case, that in which the isokinetic relationship itself and the correlations with the parameter are very precise. Various algebraic expressions and various graphic representations of the isokinetic relationship offer the possibility of investigating each particular case from different sides and of stating the results and their consequences. A given kind of representation can be useful in a particular case, and n o one of them can be considered to be erroneous in itself.

THE ENTHALPY-ENTROPY RELATIONSHIP

427

However, large errors can arise when the regression is attempted in improper coordinates, or, what is equivalent, if a line is drawn approximately through a given set of points. Unobjectionable statistical means are now available (Section IV.) to decide whether the relationship holds and t o obtain the value of p . The purpose of various graphs is only to represent objectively the results obtained. Having in mind the various forms of the isokinetic relationship, we can also show its physical meaning in kinetics more clearly. Let us consider a reaction series with a variable substituent, solvent, or other factor. The term “reaction series” was discussed by Bunnett (14), with the conclusion that the common mechanism of all reactions is a necessary condition (1 2). However, this condition can seldom be ascertained, and best after finishing the whole analysis. At the beginning, it may be sufficient that the reaction products are invariable and the kinetic order equal. In addition, the structural changes should not be too large; of course, this condition cannot be defined precisely. The differences in reaction rates at a given temperature are now explained in terms of substituent inductive and mesomeric effects, steric strain, steric hindrance, or similar theories which give the substituents a certain sequence. When the kinetic study is now extended to other temperatures, the existence of the isokinetic temperature warrants that this sequence does not change. It is evident from Figure 5, where the individual lines d o not cross. Hence, an interpretation valid at a certain temperature can be retained in the whole interval. In addition, the activation enthalpies or entropies give the same sequence as reaction rates and can be discussed in the same terms. Therefore, it would be desirable to show that the isokinetic relationship held, at least in theoretically important reaction series. However, a new difficulty arises when the isokinetic temperature can be reached experimentally. At this temperature, all reactions of the series should proceed by the same rate, and when passing over it, the sequence of reactivity should be reversed (see Figure 5). Since substituent effects and similar factors cannot change their sign, the only explanation of this phenomenon remains that the susceptibility of the reaction to these effects has been reversed; it would follow that the mechanism is not so simple and that the transmission of substitution effects is not straightforward. The experimental evidence is very scarce and in most cases the isokinetic temperature is far from experimentally realizable and can be viewed rather as the product of extrapolation without any real physical meaning. The isokinetic relationship can further yield a preliminary test of a common mechanism: i.e., when one reaction deviates from the others, it follows to a high probability that its mechanism is different. The deviations are best seen in a plot like Figure 4, while in Figure 5, it is difficult to decide which of the straight lines does go through the common point of intersection.

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IV. STATISTICAL TREATMENT

A. General Problems The danger of an incorrect statistical treatment was anticipated by many workers(1-4,6,31,115, 116,119, 121-137,142-158),butthewarningswerein general insufficient. In order to see the problem in its full import, let us consider the following example: Hydrolysis of various alkyl-substituted succinic and glutaric anhydrides was followed (202) at pH = 5.20 and at temperatures 293, 298, and 303°K. Values of E* and AS* computed for each compound were plotted against each other (Figure 6 ) , and two lines with slopes 290 and 320" K were found for sterically less hindered and more hindered derivatives, respectively (202). However, the plot of log k303 against log kZg3 shows only one straight line (Figure 7) with a slope a little less than unity (full line). The

Figure 6. Real (full line) and apparent (broken lines) relations in the graph E* versus AS*, hydrolysis of cyclic anhydrides (202).

THE ENTHALPY-ENTROPY RELATIONSHIP

429

significance of the straight lines in Figure 6 can be tested as follows. Let us choose two points on each line, representing two fictitious compounds for which the linear relationship holds exactly. From AS* and E* of these fictitious compounds, the corresponding values of log k293and log k303can be computed, plotted in Figure 7, and connected with a straight line. By this procedure (149), the broken lines have been mapped from Figure 6 into Figure 7: alternatively, eq. (15) could be used to compute its slope, b. It follows from Figure 7 quite objectively that both broken lines have no physical meaning and no relation at all to the experimental facts: they are pure artifacts that result only from the computational process of E* and AS* from the rate constants. By a reversed procedure, or by means of eq. (1 5), the real regression line can be mapped from Figure 7 into Figure 6 (full line). It has the slope 862°K and is not directly related to the plotted points and cannot be detected in this graph. Note that by an anparently unambiguous procedure, results hwe been obtained which

Figure 7. Real (full line) and apparent (broken lines) relations in the graph log k, versus log k, , the same reaction series as in Figure 6 .

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completely disagree with the original experimental facts. This failure is not concerned with experimental error, which has not yet been taken into account. Let us still observe the Arrhenius plot of the same data (Figure 8). No common point of intersection is evident like that in Figure 5. The relationship expressed by the two broken lines in Figure 6 would require one point of intersection at T = 320°K for the slower reacting compounds, and the other one at T = 290°K for the faster reacting compounds. The Arrhenius lines going

Figure 8. Real (full lines) and apparent (broken heavy lines) isokinetic relations and experimental Arrhenius lines in the graph log k versus T-'; the same reaction series as in Figures 6 and 7.

THE ENTHALPY-ENTROPY RELATIONSHIP

43 1

through these points are shown in Figure 8 by heavy broken lines for derivatives 1, 5, 6 , and 19; they deviate badly from experimental points and cannot even be accepted as gross approximations. The real regression line from Figure 7 (full line), corresponding to the isokinetic temperature 862” K, would require the Arrhenius plot shown by full lines in Figure 8 for compounds 1 and 19 only: they are almost identical with the experimental ones. Clearly, one cannot decide without a fine statistical test whether the experimental lines in Figure 8 really intersect at T = 862” K or in another point, or whether they are parallel. Let us now consider the experimental error and its representation in Figures 6 through 8. The simplest situation is in Figure 8, since temperature can be taken as an exact quantity* and error in logk can be relatively easily estimated. There is a usual assumption that relative errors in k are constant throughout the reaction series, so that absolute errors in log k are also the same (142, 144, 153). As a typical value for kinetics in solution, the accuracy +5%in k is usually taken (or at best 3%) corresponding to k.021 log units (or k.013) in log k. However, the errors may be still larger when measurements from different laboratories are compared. Although such figures are quoted in numerous papers, there is no agreement about their exact statistical meaning. In fact, the only useful quantity is the standard error 6 or its estimate. The term “maximum possible error” (144) is itself meaningless unless we understand it as a certain multiple of the standard error: e.g., 26 or 36. The usual claim of a maximum error of 5%can thus be understood as standard error of some 2-3%. In Figure 8, the error k5% is shown by abscissas on line 3. In the graphs of log k, versus log k 2 , independent errors of the same magnitude in both directions can be anticipated. Hence, they can be represented by the usual circles. That is, if this radius equals the standard error 6 (or 26), it means that the actual value is situated inside with a probability of .393 (or .865) according to the x2 distribution with two degrees of freedom (204). The circles in Figures 4 and 7 correspond to an error of 5% in k. Alternatively, the experimental error can be given a particular value for each reaction of the series, or for each temperature, based on statistical evaluation of the respective kinetic experiment. The rate constants are then taken with different weights in further calculations (205,206). Although this procedure seems to be more exact and more profoundly based, it cannot be quite generally recommended. It should first be statistically proven by the F test (204) that the standard errors in fact differ; because of the small number of measurements, it can seldom be done on a significant level. In addition, all reactions of the series are II priori of the same importance, and it is always a

* In this conception (149), any value of T denotes the exact temperature at which it was intended to carry out kinetic measurements; experimental errors in thermostating appear in errors of log k. The approach is fully correct from the statistical point of view (203) and much simpler than to consider errors in T, too.

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shortcoming if some of them should be excluded or taken with a lesser weight. The effort of the experimenter should rather be directed to bring all measurements to comparable accuracy. On the other hand, the same accuracy at different temperatures may not be feasible, and weighting of the data is inevitable. Activation parameters are always computed from rate constants, and their errors are functions of errors in logk. If the reaction is followed at two temperatures only, the pertinent formulas read* (142):

where 6 is the standard error in log k, equal for the two temperatures. The value 2.3036 is the relative error i n k , taken as small compared to k. It follows that the errors 6,$ and 6 s $ are approximately in the ratio T : 1, and both are much larger than errors in log k. More exactly, the errors in AHS and in TASS are larger than those in ACT (SGS = 2.303 RT6) in the ratio t/ZT : (T, - TI). This ratio is still more unfavorable if averaged values of AG are calculated based on all measurements: with two measurements, the error ( 6 ~ is) lessened by the factor l/&. The relations shown are not altered when rate constants at several temperatures have been measured and the activation parameters are computed by linear regression in the coordinates log k versus T-'. The estimates of error can then be obtained, instead of from the accuracy of individual kinetic measurements, from the accuracy of regression log k versus T-'according to the known formulas?

where s , . ~is the standard deviation from the regression line, given by

* Essentially the same formulas for S H S are given in (144),whereas that for 6sS differs, since it is based on computation of A S $ from log k and AH$, whose dependence is disregarded. t See (204, 207) for common statistical terms and basic relations.

THE ENTHALPY-ENTROPY RELATIONSHIP

433

sk and sT are the mean square deviations of the variables log k and T-’ from their averages and r is the correlation coefficient in the coordinates T-’ and log k. Equations (22) through (24) show again that errors in AH* and TASS are of the same magnitude-see particularly the right-hand part of eq. (23)-and much larger than errors in AGS. With an increasing number of measurements, the situation is practically not changed. If different errors are obtained for individual reactions of the series, they can be averaged for the reasons mentioned, unless the differences are very large. In graphs of AHS versus AG* or AS* versus AGS it is thus sufficient to show the error in the ordinates as in Figures 2 and 3 a t the points for 4-Me and 4-OMe. The threefold standard errors given in the original literature (69) were used, computed for each reaction separately. When errors in the graph of AHS versus ASs are to be pictured, one must take into account that they are mutually correlated, since any error in determining the slope brings error in the same direction in the intercept (see Figure 5). A “point” in this graph cannot be represented by a circle, but rather by an eccentric ellipse (143, 149). The direction of its main axis is somewhat dependent on the choice of scales for AH* and AS*, but close to the harmonic mean temperature T.* Since the ellipse is very eccentric, it can be represented as an abscissa corresponding t o the main axis. In Figure 6, point 17, it was computed according to eqs. (22) and (23), taking approximately .007 for ~ y . ~in; Figure 1, threefold standard errors from the original literature (69) have been used. In the graph of AH versus AS, large deviations in the direction of T are thus admissible, while much smaller ones in the perpendicular direction are not. Hence, sequences of points with the slope T can easily result from experimental errors only: this is why the value of T is called error slope (1-3, 115, 116, 118, 119). Isokinetic relationships with slopes close to T should be viewed with suspicion, but they have been reported frequently. However, we shall see later that even correlations with other slopes are only apparent, or at least the isokinetic temperature is determined erroneously from the plot of A H versus AS. As t o the computation of reaction enthalpies and entropies, AHo and ASo, the same arguments apply if they have been obtained from the temperature dependence of the equilibrium constant. A different situation arises when AHo is determined directly from calorimetry, say with a constant relative error 6’. The standard entropy ASo then has the standard error

6s = d(6’/T)2 + (2.303 R6)2

(26)

and is usually more accurate than values from kinetic data. Furthermore, the errors in AHo and ASo are less correlated than in the above case. The contour of

* Exactly, the mean temperature should be defined by 2/T* = 1/T: + 1/T: in the case of two temperatures, but the difference from the harmonic mean is small.

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a “point” is an ellipse which is not so eccentric as in the above case. However, the natural and only correct representation is the plot of AHo versus AGO. The unsymmetrical error contours of points, especially in the graph A H versus AS, represent one reason why one is not allowed to draw a regression line in just any system of coordinates. Since deviations in various directions are not equivalent, it is not possible to estimate the right position of the line, nor can the regression analysis be applied in simple form. However, the existence of experimental errors is not the only reason for difficulties, as many authors believe (1-3). The situation would be essentially the same if the experimental points were absolutely precise and an approximate relation between them was sought. Simply, the regression of a priori dependent variables does not agree with the presumptions involved in the regression formulas and is not allowed. In the following sections, simple approximate statistical procedures, as well as more sophisticated ones, will be given, which are all free from this shortcoming.

B. Kinetic Measurements a t Two Temperatures The simplest problem, but a rather frequent one in practice, arises when a reaction is followed at two temperatures only (Tz > T J and the activation parameters are computed using the equations

A simple and correct treatment of the data (149) consists of plotting log k2 against logkl, drawing a straight line with the slope b, and calculating the isokinetic temperature /3 according to eq. (1 5). In this procedure, eqs. (27) and (28) are viewed as a transformation of coordinates in the plane, the original coordinates x log k l and y log k2 being replaced by new ones x t log A and y’ E*. In geometric terms, this kind of transformation is called “affinity,” if we disregard the constant coefficients and the consequent change of scale. It can be resolved into a homologous affinity, with the y axis as the affinity axis and the direction of the affinity at the angle 45” to the x axis, and a subsequent rotation around the origin by -45”. The origin of coordinates is the invariable point of the whole transformation; parallel lines are mapped again as parallel lines and an ellipse as an ellipse (or circle). However, it can be shown easily that a regression line of a given set of points does not remain the regression line after the transformation, and also that the correlation coefficient is altered. Let us denote in the original coordinates log kz versus log k,; r 1 2 , the correlation coefficient; bz.l and l/bl.Z the slopes of

THE ENTHALPY-ENTROPY RELATIONSHIP

435

regression lines; and sl, s 2 , standard deviations of log k l and log k2 from their averages. After transformation to coordinates log A, E*, the correlation coefficient, r34, is given by

It follows that r12 = 1 implies also that r34 = 1. Usually, r34 > rI2; e.g., when r12 = 0, r34 is positive and higher the smaller the interval (Tl, Tz). For example, for TdT2 = .9 and s 1 = s 2 , we get the surprisingly high coefficient r34 = .9986. This extreme case is worth a diagram (Figures 9 and 10). There is shown a completely artificial correlation due not to experimental errors-which can be arbitrarily small-but to the inhomogeneity of the reaction series. One can further compute the slopes b;.] and l/b;.z of the real regression lines, drawn in the log k2 versus log kl plane and transformed into the E* versus log A plane :

2 hi kf

Figure 9. An artificial extreme cases of‘ a reaction series with no correlation between log k, and log k , .

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IU~A

Figure 10. Transformation of the reaction series from Figure 9 into the coordinates E* versus log A.

These lines are generally different from the regression lines drawn in the E* versus log A plane, which have slopes b4.3 and l/b3.4

Both pairs of lines are identical only when r12 = 1 ; in this limiting case, all four expressions in eqs. (30) and (31) are equal, and statistics has been replaced by simple geometry. If there is n o correlation at all between the original values log kz and log k,, i.e., rl2 = 0, apparent regression lines are obtained in the E* versus log A plane (Figure 10) with the slopes (when sl = s2) b4.3 = 2.303 RTITz(T1 +Tz)/(T: +T:) (32) l/b3,4 = 2.303 R2TIT,/(T, +T2) The latter is the mentioned error slope (1-3, 115, 116, 118, 119). In this case, it

THE ENTHALPY -ENTROPY RELATIONSHIP

431

does not arise as a consequence of experimental errors, but results only from the condition r12 = 0. Example 1. Lossen rearrangement of potassium salts of disubstituted dihydroxamic acids was followed kinetically at 30" and 40°C (208). Several compounds were measured at 20" and 30°C: for these, the missing value for log k40 can be obtained by extrapolation. From the plot of l o g b O against log k30 (Figure 1 I), one can conclude either that the compound 4 does not belong to the series or, more probably, that the deviation can be attributed to a gross error. When the deviating point is disregarded, a line can be drawn, as estimated in the plot, with the slope b = .97, and 0 is computed from eq. (15) to be -4664°K. The value of 0 is rather uncertain: a slope b = .96 or .98 would correspond t o f l = t1505" and -507"K, respectively. Clearly, an infinite value of 0, corresponding to the hypothesis of a constant entropy throughout the reaction series, cannot be rejected. By plotting E* versus log A, Figure 12 is obtained, where the real regression is shown by a full line. The broken line, which would be drawn in the plot of E* versus log A, would be influenced by the remote point 4. From the analysis in these coordinates it was concluded erroneously that the isokinetic relationship does not hold (I).

-1

-

-2

-

-3

-

1

-3

-2

lllku

Figure 11. Isokinetic relationship for the Lossen rearrangement of dihydroxamic acids (208), in the log k, versus log k , plot, real (full line) and apparent (broken line) relations.

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The experimental error was estimated as 1-4%in k (208). In Figure 1 1, the more skeptical value of 5% is shown; in Figure 12, the corresponding errors in E* and logA are pictured at the point 29. In the coordinates logk2 versus log kl, the correlation coefficient can be computed as r12 = .9919 or .9991, with or without the point 4, respectively. The corresponding standard deviations from the regression lines are .068 and .022 log unit, respectively. Their difference justifies the exclusion of point 4; the latter value compares favorably with the estimated error of 5% in k = .021 log unit.

I

I

,

1 ti

Figure 12. Isokinetic relationship for the same reaction series as in Figure 1 1 , in the coordinates E* versus log A.

The method outlined is quick and useful for testing isokinetic relationships described in the literature and for finding approximate values of p (149). It should replace the incorrect plotting of E* versus log A, which gives fallacious results for the value of and which usually simulates better correlations than in fact apply. Particularly, the values of correlation coefficients (1) in the E* versus log A plane are meaningless. As shown objectively in Figures 9-12, the failure of this plotting is not caused by experimental errors only (3, 143, 153), nor is it confined t o values of 3./ near the error slope or within the interval of experimental temperatures (1 5 1).

THE ENTH ALPY-ENTROPY RELATIONSHIP

439

There are, however, three limitations of this method. First, when the interval of experimental temperatures is too narrow, no significant results can be obtained. The correlation coefficient in the coordinates log k versus log k2 is near unity without having any physical meaning, and the slope b is also so close to unity that the difference cannot be stated. In Example 1, this difference may still be just significant: see Figure 1 1. However, in general, a temperature interval of 10" is not sufficient. It is recommended in such cases to plot E* versus log k to obtain the crude picture (149): however, the complete statistical treatment (Sec. IV.C., Example 3) is to be preferred to prove whether significant results can be obtained or not. Second, the method was devised as a quick graphic procedure. If it should be refined by introducing statistical methods, the problem arises as to which kind of regression is appropriate in the log k2 versus log k l plane. Normal regressions of log k, on log k2 or vice versa (1 55) are not correct, since neither log k l nor log k2 is an exact quantity. Therefore, a graphic estimate is preferred in Example 1 ; in eqs. (30) through (32), the two regression coefficients were given only to show how they are changed by coordinate transformation. The appropriate regression minimizes deviations in the direction normal to the regression line (207): its slope b = tan cp is given by tan 2 p = 2sls2r12/(s: -s;)

(33)

when the symbols used hitherto have been introduced. However, if this regression is used and p is computed from eq. (IS), exactly the same formulas-eqs. (46) and (47)-are obtained (163), as developed in Sec. IV.C., and the method thus loses independence. Finally, the method is confined to measurements at two temperatures, constant for the whole reaction series. A few lacking data can be gained by extrapolation without affecting markedly the overall accuracy, as in Example 1. If more reactions of the series have been studied at deviating temperatures, or at more than two temperatures, there are the following possibilities: The more sophisticated methods of Secs. 1V.C. and 1V.D. are applied, the graph log k2 versus log k , being used for preliminary information and to control the results. Alternatively, the Arrhenius plot can be constructed for each reaction and two points are chosen on each line at fixed temperatures, representing extrapolated measurements, log k l and l o g k 2 , which are treated in the usual way (188). However, the simplicity of the procedure is lost by this generalization, and the estimation of error is made difficult. Another procedure advanced, i.e., to compute p from all combinations of log ki and log kj at all temperatures (155), is quite impractical and offers no possibility for finding the right value among many results.

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C. Kinetic Measurements at Several Corresponding Temperatures In order to formulate the statistical problem generally, let us return to the Arrhenius graph (Figure 5) and ask the question of how to estimate the position of the common point of intersection, if it exists (162). That is, in the coordinates x E T-' and y log k , a family of_l straight lines is given with the slopes bi (i = 1 , 2 , . . .I; 1 2 3) and with a common point of intersection (xo, yo). The ith line is determined by mi points (mi 2 2) with coordinates (xij, yb) where j = 1 , 2 , . . ., mi. Instead of the true coordinates yi,, only the values yi, = yi, + eG are available, eij being random variables with a zero average value and a constant variance, a'. If the hypothesis of a common point of intersection is accepted, eij may be identified with the experimental error. The task is to estimate the parameters xo(=fj-'), y o , b, and u. In the framework of the least-squares method, we obtain the estimates i of0 , arid bi by solving the normal equations' y.. = yo - %o C mihi/ C mi + i

i

o = go C mihi

~~

k0 C mi6f

i

--

i

1

C mi6ixi.l C mi I

C mibiyi,+ C miS?xi, i

I

(34)

j

where xi. stands for

This system of L + 2 equations is nonlinear, and for this reason probably has not received attention in the least-squares method (207). We are able to give an explicit solution (163) for the particular case when xi, = xj and mi = m for all values of i: that is, when all reactions of the series are studied at a set of temperatures, not necessarily equidistant, but the same for all reactions. Let us introduce pi

=

C x,yi,/m

-

xyi.

(35)

j

where X is the average value of xj. We then obtain Go as

where uo is a root of the quadratic equation

* Quite recently, Thorn has derived an essentially identical set of normal equations when analyzing the vapor-pressure-temperature relationships (209): he did not deal with its solution.

THE ENTHALPY-ENTROPY RELATIONSHIP

1

+

; ;C (xj - x)' J

C (Pi 1

--

P) (Yi. -Y.) = 0

44 1

(37)

This equation always has a real solution. Of the two roots, one corresponds to minimum sum of squares, i.e., the desired value, xo = b - ' , which is computed with a positive sign at the square root. Once uo is found, 30 and Abi are given by eqs. (38) and (39) and the residual sum of squares So by eq. (40):

The slopes bi are connected with activation energies of individual reactions, computed with the constraint of a common point of intersection. We called them the isokinetic activation energies (163) (see Sec. VI). The residual sum of squares So has (m - I)& 2 degrees of freedom and can thus serve t o estimate the standard deviation u. Furthermore, SO can be compared to the sum of squares Soo computed from the free regression lines without the constraint of a common point of intersection

with (m - 2)ldegrees of freedom. Of course, Soo< S o ; if the difference is significant, the hypothesis of a common point of intersection is to be rejected. Quite rigourously, the F test must not be used to judge this significance, but a semiquantitative comparison may be sufficient when the estimated experimental error 6 is taken into consideration. We can then decide whether the Arrhenius law holds within experimental error by comparing Soo/(ml-- 21) with 6' and whether the isokinetic relationship holds by comparing So/(ml - 1- 2 ) with 6'. If Soo= S o , all regression lines intersect in one point; the corresponding condition reads

It is, of course, fulfilled identically when there are only two straight lines (1= 2).

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442

Finally, it is possible to get an idea about the error in 0 or its confidence interval. Let us choose an arbitrary temperature, TU(# /3), corresponding to the abscissa of the supposed point of intersection (u, y,), where u = T i ' - X, and let us search for optimum values yu and bi,u to minimize the residual sum of squares S,(S, > So). The solution is given by eqs. (38) and (39) with u instead of Go, and the desired sum of squares equals

s u = C (Yij - Y . . ) ~ ij

and has (m 111- 1 degrees of freedom. The dependence of Su on u is interesting. It can be represented by a curve of the third order with an asymptote parallel to the x axis, with a minimum at the point u = ua, and with a maximum. The plot of the corresponding standard deviation S O is similar (Figure 13). On the other hand, the dependence of y, on u is linear: that is, all supposed points of intersection are situated on a straight line (the dot-and-dash line in Figure 13). When the value Soo (or the corresponding soo) and the experimental error are shown, this plot pictures the result of the whole analysis. Quite often the function is so flat in the vicinity of the minimum that the isokinetic temperature cannot be given any distinct value. This may happen even when the hypothesis of a common point of intersection cannot be rejected: the results are then to be formulated that the isokinetic relationship holds but that a more definite value of /3 is not known. For a more detailed analysis of the function S, and some special cases, see (1 63). For practical calculation on a desk calculator, the following transformation is strongly recommended: ~

Define pi as before in eq. (35):

and calculate first the following auxiliary quantities:

THE ENTHALPY-ENTROPY RELATIONSHIP

44 3

Figure 13. Isokinetic relationship for the reaction of substituted dinitroniethanes with formaldehydes (57). The standard deviation is shown as function of the supposed isokinetic temperature (full curve).

P=m i

Q=m

pi =

Cij uj log kij

C p? = & c i

i

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444

In practical calculations, the right-hand sides of eq. (44) are used. The quantities needed are then obtained from the modified eqs. (37) through (41)

C += [Q T:'

uo = p - I -

-

Pz/ml- XY - J(Q - P / m l - X Y ) ~t X U ~ I / U

(37a)

j

f = (m

~

1)l- 2

So0 = Z - Y -Q/X

f=(m-2)1 Finally, S, may be calculated for various values of u and plotted.

s, = z -

Q - UUt u2(Y t P*/mlX) -

(43a)

xtu2 f = (m

~

11- 1

When the whole procedure is applied to kinetic data related to two temperatures only (Tz > Tl), it can be further simplified. Let us denote

and introduce the following auxiliary symbols, the number of which is restricted because of the constraint Soo = 0.

Values of /3(uo), y o , bi, So and S, are then obtained from the modified equations

THE ENTHALPY-ENTROPY RELATIONSHIP

445

T1+Tz T uo = p - ' - _ _ _ - _ _ [ 2 M t d 4 M Z t(N-L)'] 2TITz N - L

(47)

1 So = - [ L + N - d 4 M 2 +(N-L)'] 2

s

u

= -L. +t N 2

?M

-

UT(N- L) -u'M T2

+U2

Example 2. Equilibrium constants of the reaction of twenty substituted dinitromethanes with formaldehyde have been measured (57) in the range 10-50°C. The isokinetic relationship is valid for only nine of them, as revealed in a preliminary graphical treatment using the plot of log KSO versus log Klo(l 63); the pertinent values of log K are reproduced in Table I. The values of x = T-' were transformed according to eq. (36a) with

ci Tj-'/m

= .00332232,

and the auxiliary quantities were calculated by use of eqs. (44) with m = 4,1= 9: TABLE I Equilibrium Constants (57) of the Reaction RC(NO,),CH,OH + OH- * RC(NO,); +CH, (OH),

No. 5 6 7 8 9 10 12 14 15

R

283°K

293°K

5.64 5.57 6.28 6.03 6.26 6.86 6.58 7.21 7.37

5.63 5.59 6.20 5.98 6.18 6.80 6.55 7.1 1 7.25

log K 308°K

5.57 5.55 6.10 5.88 6.1 1 6.63 6.36 6.88 7.01

323°K 5.51 5.48 5.96 5.76 5.97 6.41 6.1 8 6.63 6.7 1

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X = 2.744615 x Y = 9.90428, Z = 10.74796, P = 8.044398 x Q = 2.256174 x lo-', U = 4.225005 x From eq. (37a), we get ; the original literature (57), uo = -.00128641, corresponding to 0 ~ 4 9 1 ° K in the value p = 690 f 90°K was obtained for 11 derivatives by an improper statistical procedure. Further, according to eqs. (40a) and (41a), So = .02452 with f = 25, and Soo = .02164 with f = 18, corresponding to so = .031 and soo = .035 log units, and yo = 5.225 log units according to eq. (38a). The value of soo reveals that the experimental error given (57) as .01 to .02 log units may be somewhat underestimated. The isokinetic hypothesis must be accepted unconditionally since so < soo . Finally, S, was computed for various values of u according to eq. (43a), and the corresponding standard deviation s, (with f = 26) was plotted against u, Figure 13. When one admits the standard error, say .04 log units, the confidence interval of 0 is from 425" to 700°K. The hypotheses can be rejected that the series is isoenthalpic (s- = .085 log units) or isoentropic (s, = .060 log units). This example shows that the value of 0 is imprecise even when the validity of the isokinetic relationship has been proved without any doubt. Example 3 . The data from Example 1 (208) were recalcuiated I J ~the formulas (45)-(51) with the following results: uo = -184801 x l o - * , 0 = 714"K, yo = 8.14 log units, so = .048 log units; s, is plotted in Figure 14 with a broken line. When the deviating derivative (see Figure 11) is eliminated, these values change to uo = -496921 x 0 = -581"K, yo = 26.48 log units, so = .016 log units; s, is plotted in Figure 14 with a full line. The improvement obtained is highly significant even at a = .005, and the graphical representation confirms that the elimination of this derivative (dashed straight line in Figure 14) was justified. The simple mathematical treatment cannot reveal such a deviation, and for this reason the. preliminary graphical treatment, as in Figure I 1, is stlongly recommended. The "experimental accuracy" was estimated (208) to .OW-.016 log units in an individual measurement, the upper limit being probably more realistic. Hence, the hypothesis of a common point of intersection cannot be rejected: on the other hand, the isokinetic temperature cannot be given any definite value. Neither any value higher than 600°K nor any negative one can be disproved. This statement follows from the curve in Figure 14, as well as from the comparison of estimates of I3 in Example 1 and Example 3. Figure 14 thus shows objectively the weakness of all arguments based on an insufficient number of measurements in a narrow temperature interval, even when the number of reactions is relatively large. (Only five reactions from twenty-four are shown in the figure.) The applicability of the procedure outlined is limited by the following factors. First, the set of experimental data must be complete: i.e., each

THE ENTHALPY-ENTROPY RELATIONSHIP

441

I

\\\

rrk

20

10

\

0

I -2

I

I

0

2

4

r4103

Figure 14. Isokinetic relationship for the same reaction as in Figures 11 and 12, with the standard deviation shown for all reactions (broken curve) and with one reaction excluded (full curve).

reaction should be followed at all temperatures. In a set of, say, twenty data, it is possible to add one lacking figure by interpolation or extrapolation without affecting the overall results. Otherwise, the method of the next section is to be employed [see eqs. (52)-(55)]. Second, all of the measurements must have the same weight: i.e., the same accuracy was assumed in deriving the equation (34). The value of u thus corresponds to the standard experimental error. It is always a limitation when different weights are given to each reaction of a series, and this should not be done without good grounds. A more appropriate solution could be to divide such a series into subgroups or to eliminate some members. The graphical representation as in Figure 11 may be useful in this connection. One also can see from this representation whether the caiculation is worthwhile at all. More frequently, the accuracy attained may depend on temperature. In this case, the weights can in principle be incorporated into the calculation: however, it may become so complicated that the use of eqs. (57)-(60) and a computer is preferable. Finally, this procedure was devised for a desk calculator and is convenient only in combination with this technique. If a computer is used,

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448

the explicit solution has no advantage, and the general program, outlined in the next paragraphs and based on iteration procedures, is more suitable.

D. Kinetic Measurements at Arbitrary Temperatures If the explicit solution cannot be used or appears impractical, we have to return to the general formulation of the problem, given at the beginning of the last section, and search for a solution without any simplifying assumptions. The system of normal equations (34) can be solved numerically in the following simple way (164). Let us choose an arbitrary value x(= T-') and search for the optimum ordinate of the point of intersection y(= log k) and optimum values of slopes bi to give the least residual sum of squares S, (i.e., the least possible with a fixed value of x). From the first and third equations of the set eq. (34), we get

(7

xij -mix)

y..-

(7

CJ Yil)

xijyij - X

-

C x i - 2 ~C x i j t m i x '

ij

j

y=--

(F

J

(52)

xij - m i x r

_ _ _ 1i mi - C - 1- x~ i_- _2 _~C- -xij+mix2 j

j

without using the symbols pi, xi. and y.., which are not practical in this case. For the residual sum of squares S,, we get

I

By repeating the calculation for various values of x, one can obtain y and S, as functions of x and find the minimum of the latter by successive approximations. The value of x at this minimum (xo) gives the estimate of the isokinetic temperature xo =p-'. The corresponding values yo and So are obtained from eqs. ( 5 2 ) and (53); So has mi -1- 2 degrees of freedom. I

From the plot of S, versus x , the confidence interval of xo can be estimated.

THE ENTHALPY-ENTROPY RELATIONSHIP

449

Further, the values of the slopes bi can be calculated on the basis of eq. (34): i.e., explicitly,

Through bi, the so called isokinetic activation energies (163) are defined: see Sec. VI. The whole procedure has been programed for a small computer (164). Values of y and S, corresponding t o equidistant steps in x are given in the output in order to be plotted in the graph. To find xo, the interval of x is refined several times: however, a high accuracy is excessive with respect to the inherent uncertainty in X O . Finally, the values of x o , y o , SO, S o o , bi and the corresponding isokinetic, as well as nonisokinetic, activation energies and entropies are given in the output. The symbol Soo denotes, as formerly, the residual sum of squares without the constraint of a common point of intersection and is given in this case by

The whole calculation can also be extended easily to measurements of different weights, i.e., of different accuracy. Let us denote the standard error in yij by tiij. The weight wij of a measurement can be defined as

and eqs. (52)-(55) are modified to

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s, =

c i

The standard deviations so and soo , corresponding to So and Soo, respectively, can be compared to each other and to the mean experimental error. Let us mention once more that different reactions should be given different weights only if there are very good reasons and no other way out. The general properties of functions y = f(x) and S, = f(x) expressed by eqs. (52) and (53), respectively, have been studied in an orienting manner (164). Both are rational fractions and continuous for all values of x. The former has a polynomial of the 21- 1 degree in the numerator and of 21- 2 degree in the denominator and one asymptote with the slope

In cases similar to real kinetic measurements, the curve does not go too far from

THE ENTHALPY-ENTROPY RELATIONSHIP

45 1

its asymptote and has no maximum or minimum (see Figure 1.5). By the constraints xij = xj and mi = m, the curve is reduced to its asymptote: eq. ( 5 2 ) changes t o eq. (38). The function S, = f(x) is a ratio of two polynomials of the 41 - 2 degree and is always continuous, finite, and positive. It has one horizontal asymptote at S, , given by

The quantities b, and S, represent the solution of the problem of drawing para!lel lines through the given set of points by the method of least squares. They are obtained relatively easily and can serve to check the whole calculation. The function S, = f(x) always has a minimum: however, the conditions have not been explored when it has only one minimum. This case would be important from the theoretical point of view: however, in practice there is no real danger

Figure 15. Disproved isokinetic relationship for the proton transfer from nitromethane t o various carboxylic acid anions (156). Symbols as in Figure 13.

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of finding a local minimum instead of the absolute one, especially when the calculation is monitored by a graphical representation. In practical examples, the function has one minimum and one maximum and its shape resembles that given by eq. (43): compare Figures 13 and 15. By the modifications, qj = xj and mi = m eq. (53) turns into eq. (43), of course. Example 4. Second-order rate constants of the hydrogen transfer from nitromethane t o anions of various carboxylic acids have been measured at lo", 20", 30", and 40°C in two cases, at 15", 20", 25", and 35" in two other cases, and at 15", 25", and 35°C in the remaining fifteen cases (156). All of the data have now been processed together by use of a computer program ( I 64) based on eqs. (52)-(55), without respect to different accuracy given for individual values corresponding to (1 56). The following results were obtained: xo = 1540 x , corresponding to so = .039 0 = 649°K; yo = 4.25 log units; SO = 61831 x log units; Soo= 11759 x , corresponding to soo= .023 log units. The dependence of s, and y, on the supposed isokinetic temperature is shown in Figure 15 by the full and dot-and-dash curves, respectively; the latter is practically a straight line. The value of soo agrees reasonably well with the experimental error, estimated for individual rate constants as .001 to .086 log units. The difference between so and soo is large enough to reject the isokinetic hypothesis even at the confidence level a = .005. The hypotheses that the reaction series is isoenthalpic (s, = .065 log units) or isoentropic (s, = .046 log units) must be rejected with still higher probabilities. This negative result is confirmed by an attempt to estimate the confidence interval of 0.If we arbitrarily choose a standard deviation of .05 log units, values of 0 from 435°K up to infinity, as well as negative ones lower than -800°K, must be admitted. The only possibility of getting further in the analysis would be to divide the reaction series into subgroups. Alternatively, the experimental material could be extended: particularly, the temperature interval could be broadened. In this example, an approximate calculation according to the formulas of Sec. 1V.C. is also possible with use of a desk calculator. For this purpose, two constants at 20°C are simply omitted and in two further reactions the data at lo", 20", 30" and 40°C are replaced by those at 15", 25", and 35°C obtained by interpolation and adding an estimated error. The results are ; i.e., 0 = 622°K; yo = 3.92 log units; S o = 60170 x xo = 1608 x ; so = .041 log units; Soo= 11287 x soo= .024 log units; and s, is represented by a function indistinguishable from that one in Figure 15. The procedure thus seems satisfactory. The only serious difference is the reduced degrees of freedom, with the result that the isokinetic hypothesis cannot be rejected at the .005 level but only at a E .01 1. To conclude, we recommend the following procedure when treating kinetic or equilibrium data of a reaction series. The Arrhenius plot is constructed first for all of the reactions investigated in order to get the general picture. Then

THE ENTHALPY-ENTROPY RELATIONSHIP

45 3

the plot of two log k against each other (usually at the extreme temperatures) yields the basic information as to the validity of the isokinetic relationship (see Figures 4 , 7 , 11). Accordingly, the reaction series can be divided into subgroups, some reactions excluded, etc. Subsequently, the statistical treatment is undertaken, with use of the formulas of either this or the preceding section according to the character of data and technique of computation, and the isokinetic relationship is either rejected or accepted (in individual subgroups, as the case may be). Finally, a plot like Figures 13-15 is constructed and the confidence interval of 0 is estimated.

E. Calorimetric and Equilibrium Measurements In equilibrium measurements, there is the possibility of determining the reaction enthalpy AHo directly from calorimetry and of combining it with log K (i.e., AGO) to get the reaction entropy, ASo. This case, advantageous and simple from the statistical point of view, was only mentioned in a previous paper (149). Since that time, this experimental approach has been widely used (59, 62-65, 74-78, 134, 137, 138, 210, 211): hence, a somewhat more detailed mathematical treatment seems appropriate. The natural and correct form of the isokinetic relationship is eq. (13) or (13a). The plot, AHo versus AGO, has slope p/(p - T), from which 6 is easily obtained. If a statistical treatment is needed, the common regression analysis can usually be recommended, with AGO (or logK) as the independent and AHo as the dependent variable, since errors in the former can be neglected. Then the overall fit is estimated by means of the correlation coefficient, and the standard deviation from the regression line reveals whether the correlation is fulfilled within the experimental errors. However, it is not proper to apply the regression analysis in the coordinates A P versus ASo or ASo versus AGO, nor to draw lines in these coordinates. The reasons are the same as in Sec. IV.B., and the problem can likewise be treated as a coordinate transformation. Let us denote rGH as the correlation coefficient in the original (statistically correct) coordinates AHo versus AGO, in which SG and SH are the standard deviations of the two variables from their averages. After transformation to the coordinates TAS' versus AGO or AHo versus TASO, the new correlation coefficients rGS and rSH , respectively, are given by the following equations. (The constant T is without effect on the correlation coefficient.) rGS =(SHrGH -SG)(sb -2SGSHrGH +s&)Jh rSH

=(sH

-SGrGH)(Sb -2SGSHrGH ts$Ah

(63)

(64)

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45 4

The new correlation coefficients, rGS or rSH , are higher than the original one, rGH, when the inequalities (65) or (66) hold, respectively. SG

>~

SH

>~ S G ~ G H

(65)

S ~H G H

(66)

This means that if the variance in AH' is the larger, the plot of AHo versus TASo simulates an improved correlation; if the variance in AGO is the larger (more frequently), the same applies to the TAS' versus AGO plot. Both kinds of plot can show an improved correlation only if rGH< 4. Figures 16 and 17 illustrate the last mentioned case using the ionization of substituted acetic acids (7.5). Although the reaction series was restricted to structurally similar derivatives of the type XCHzCOOH, there is no correlation of experimental AGO and AH'. However, the incorrect plot (75) TAS' versus AGO simulates a rather good correlation. Another possible situation could be shown in Figures 1 through 3 if the AHo data were obtained from calorimetry. Because of the high correlation coefficient in the AHo versus AGO graph, those in ASo versus AGO and AH' versus AS' are lower. The arguments do not apply to the real case shown in Figures 1 through 3, since AH' values were in fact obtained from the temperature dependence of the equilibrium constant. In this case, the only correct treatment is in the log K versus T-' plot, as described in Sec. 1V.D. \

AM kCll

\

\ o

I-' \'O \

\ \

\

\

\

\

\

r-#.f446

\

\ \

\\

-

0-

O

10

\

\

0

\ d ) O

0

b\

\

\

-1

-

-

O \

/\

" 4

-0.0944

8

\\,

\

0

0

\

\

A\

\

\ 9

I 4

I

I

I

5

a

1

AG'kd

THE ENTHALPY-ENTROPY RELATIONSHIP

45 5

Figure 17. The same reaction series as in Figure 16 shown in the coordinatesTASo versus AGO (on the left) and TAS" versus AHo (on the right). Real and apparent relations are shown as in Figure 16.

It can further be shown how the slopes of regression lines are changed during the transformation. Let bHG= s H ~ G H / s G be the slope of the real regression line in the coordinates AHo versus AGO. This line is mapped into the TASO versus AGO plane with a slope

which is identical with the slope of the regression line drawn in these coordinates when AGO is the independent variable. However, in the AHo versus TAS' plane, the slope bHC is transformed as

which is different from the two regression lines possible in these coordinates and having the slopes

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The three expressions in eqs. (68) and (69) become identical only for rGH = +1. In Figures 16 and 17, the actual regression line generated in the AHo versus AGO plot and its representation into the two remaining graphs are shown with full lines. The representation in Figure 17A is identical with the regression line generated in this graph, and differs in Figure 17B. The two regression lines corresponding to the dependence of AHo on TASO and of TASO on AHo, respectively, are shown with broken lines in Figure 17B and are mapped into the remaining plots also with broken lines. The former deviates more from the real line. We can conclude that plots of ASo versus AGO (62, 74-77) and of AHo versus ASo (63-66) are both fallacious. The former gives a wrong picture about the accuracy, usually overestimating the fit; the latter yields, in addition, a wrong value of the slope. The method of choice for calorimetric data is regression in the coordinates AHo versus AGO according to eq. (13) or (13a).

V. THEORETICAL COROLLARIES These new statistical procedures permit reexamination of a number of reaction series to reach more definite conclusions than formerly concerning the occurrence, accuracy, and significance of isokinetic relationships and possible values of the isokinetic temperatures. In this section, the consequences of these findings will be discussed and confronted with theoretical postulates or predictions . A. The Isokinetic Temperature The physical meaning of the constant 0,connected with the reversal of reactivity at the temperature T = p , is a puzzling corollary of the isokinetic relationship, noted already by older authors (26, 28) and discussed many times since (1-6, 148, 149, 151, 153, 163, 188, 212). Especially when the relative reactivity in a given series is explained in theoretically significant terms, it is hard to believe that the interpretation could lose its validity, when only temperature is changed. The question thus becomes important of whether the isokinetic temperature may in principle be experimentally accessible, or whether it is merely an extrapolation without any immediate physical meaning. Practically all values of within the experimental interval claimed in the literature (1-5, 115-1 19, 153) have been shown to be artifacts (148, 149, 163) resulting from improper statistical treatment (see Sec. IV). Petersen thus believed (148) that actually no such value had been reported, and the meaning was offered that the isokinetic temperature probably is not accessible experimentally (149, 188). This view was supported by the existence of negative

THE ENTHALPY-ENTROPY RELATIONSHIP

45I

isokinetic temperatures (124, 149, 153, 173) and by theoretical approaches representing /3 as a linear (175) or nonlinear (126, 130) function of the mean experimental temperature. The idea that /3 continuously shifts with the temperature employed and thus remains experimentally inaccessible would be plausible and could remove many theoretical problems. However, there are few reaction series where the reversal of reactivity has been observed directly. Unambiguous examples are known, particularly in heterogeneous catalysis (4, 5, 189), as in Figure 5, and also from solution kinetics, even when in restricted reaction series (187, 190). There is the principal difficulty that reactions in solution cannot be followed in a sufficiently broad range of temperature, of course. It also seems that near the isokinetic temperature, even the Arrhenius law is fulfilled less accurately, making the determination of 0 difficult. Nevertheless, we probably have t o accept that reversal of reactivity is a possible, even though rare, phenomenon. The mechanism of such reaction series may be more complex than anticipated and a straightforward discussion in terms of, say, substituent effects may not be admissible. The second question concerning the isokinetic temperature is whether it can attain arbitrary values differing from one reaction series to another or whether there are one or several characteristic values of general validity. The latter possibility follows from several theoretical considerations (6, 120, 129): particularly, it was postulated that different reaction series with the same mechanism of substituent effect should have a common value of /3 (120). In addition, a number of values for various series have been reported (1 12, 119, 135) centering around an average, usually close to the experimental temperature. Other theories (6, 102) or empirical observations (26) relate fi to the intercept in eq. (1 l), thus reducing the number of independent parameters to one: the so called hypercompensation (6). Early theories in heterogeneous catalysis connect /3 with the temperature of preparing the catalyst (27, 28). Quite often it was supposed that p can attain only a certain range of values, e.g., lower than the experimental temperature (122, 124), or only the positive ones(2, 131, 152). The reviewer is of the firm opinion that all of these findings and theories are now experimentally disproved. There is good evidence based on unambiguous statistical treatments (149, 163, 164) that positive, negative, and high as well as low values of 0 do occur, although positive ones, higher than the experimental temperature, seem to be most frequent. The reported values close to the experimental temperature (1 12, 119, 135) are certainly artifacts of the computational procedure, while the theories quoted can only be said to be at variance with the facts. The isokinetic temperature /3 is to be viewed as a constant, characteristic for a given reaction qeries-as far as this follows the isokinetic relationship-and dependent on the experimental temperature range (2, 130). It has n o immediate physical meaning and can be determined only with

45 8

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large uncertainty. Therefore, its estimation and discussion should not be the main task of the analysis, and attention is rather to be focused on the question of whether the isokinetic relationship holds or not.

B. Classification of Reaction Series Changes of activation parameters within a series of related reactions can be used for classification of these series (14, 37, 1 IS). Theoretical interpretation of reactivity should then be somewhat different in each class. In early work, attention was directed to reaction series with constant activation entropy, (34, 35, 38) which were believed to be of prime theoretical significance (16). Later, Blackadder and Hinshelwood distinguished three types (1 15, 116): 1. In series with a constant entropy, reactivity is controlled by enthalpy changes. The interpretation is usually based on electronic effects (1 2-14), which do not affect the form of the transition state, but only bond strengths (1 16). 2. In series with a constant enthalpy, controlled by entropy changes, steric effects (15), or more particularly, kinetic steric effects (13, 14) and solvent effects (14) may be decisive. 3. Changes in AH$ are paralleled by changes of ASS in such a direction that the resulting effect on reactivity is less than it would be if controlled by either A H $ or AS$ alone (compensation effect). Its cause is seen in steric or solvent effects (13, 1 16), affecting simultaneously the geometry of the transition state and the force constants (13,37, 116). 4. The fourth type was not detected in homogeneous kinetics (116) because of the unsuitable statistical treatment used, but it was known in heterogeneous catalysis (4, 5). It is the so called anticompensation, when AH$ and ASS change in the opposite sense. It was supposed that solvent effects particularly can cause such changes (37). By improved statistical procedures (149, 163), anticompensation was detected even in homogeneous kinetics and, in addition, the case of compensation could be divided into three subgroups according to the value of the isokinetic temperature. The complete list (149) is given in Table 11. The scheme is formulated for kinetics but can be applied t o equilibria without any change, since the value of 0 does not depend on the direction in which the reaction is written. However, it was argued that these classes often can hardly be distinguished in practice (1 50, 157); this is true particularly of classes 1, 3a, and 4 if fl is high in absolute value. Even the theoretical background of the classification is not clear (21). The schematic pictures in Figure 18 combine the pertinent Arrhenius plots with the functions representing the standard deviation when an arbitrary value of the isokinetic temperature has been chosen: see eq. (43). It follows from the graphs that there is in fact very little difference

THE ENTHALPY-ENTROPY RELATIONSHIP

45 9

TABLE I1 Classification of Reaction Series According t o the Relation of Activation Parameters (149)

0.

Characterization

Isokinetic temperature p

Slope b in eq. (14) Selectivity

Occurrence

isoentropic

m

T,/T,

decreases

isoenthalpic

0

1

unchanged decreases increases -

sometimes approximately fulfilled often approximately fulfilled most frequent several times found several times found

decreases

relatively frequent

compensation

anticompensation

-0.2

-0.2

0

0

>Texp 0 < b < T, /T, 0 < p < Texp >1 in the experimental
0.2

H

M

Figure 18. Schematic representation of the isokinetic relationship, a, in an isoentropic series, b, in an isoenthalpic series, c, with compensation p > TeXp d, with compensation p < TeXp

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between a series with constant entropy (Figure 18a) and one with constant enthalpy (Figure 18b). In both cases, values of /3 in a broad interval are to be admitted. Hence, it was suggested (149, 188) that the only meaningful classification is to divide reaction series into those with decreasing selectivity (with increasing temperature the reaction rates approach one another: e.g., cases 1, 3a, 4 in Table 11; Figure 18a, c) and those with increasing selectivity (case 3b in Table 11; Figure 18d). The isoenthalpic series represents a borderline (case 2 in Table 11; Figure 18b) when selectivity is not changed. The first case is quite common. Accordingly, a very reactive agent (i.e., at a high temperature) is expected to react with all substrates at the same rate. The second case is an exception and has been found only a few times (107, 149, 163): for this reason, these rare examples should receive full attention, and each such reaction series should be examined in detail. For the time being, detailed analysis is still lacking, so that the actual meaning of the classification is not known. The possibility has been advanced that this abnormal behavior may be connected with a complex mechanism consisting of more steps (163). In this way, a value of /3
Relationship Since its discovery (23), the isokinetic relationship has attracted the attention of theoretical chemists who attempted to give reasons for its existence or to predict its range of validity. They used quite different approaches in the framework of various theoretical disciplines. For this reason, the individual arguments cannot be discussed here, and an attempt is made only to confront the main results with the experimental evidence now available. The existing theoretical derivations can be divided into general theories, theories restricted to condensed systems and operating mainly with solvent effects, and special theories. The simplest derivation of the first kind starts from the theory of extrathermodynamic relationships and was presented by Leffler and Grunwald (2) and by Palm (120) in essentially identical terms. The basic assumption is a single interaction mechanism, w h c h in fact means that reactivity is controlled by a single, temperature-independent parameter. The validity of the isokinetic relationship is thus connected with the validity of an extrathermodynamic relationship at different temperatures: see Sec. V.D. Quite on the contrary, the plurality or complexity of mechanism can bring about the isokinetic relationship, too, if certain assumptions are made. Particularly, when two parallel mechanisms with different values of activation energies (ET, Eq) and preexponential factors (A,, A*) take place and only A, is being changed from one

THE ENTHALPY-ENTROPY RELATIONSHIP

46 1

reaction to another, an approximately linear relation between the effective E* and log A arises (4, 121). In other cases, there are a number of parallel processes contributing to the observed reaction rate (1 22). The pertinent theories have been developed mainly for heterogeneous catalysis (5,23,27,28,46-48). Another simple approach assumes temperature-dependent A H and AS and a nonlinear dependence of log k on T-* (123, 124,130). When this dependence is assumed in a particular form, a linear relation between AH and A S can arise for a given temperature interval. This condition is met, for example, when AC, = aT” (124, 213). Further theoretical derivatives of general validity have also been attempted: besides the early work (20, 29-32), particularly the treatment of Riietschi (96) in the framework of statistical mechanics and of Thorn (125) in thermodynamics are to be mentioned. All of the too general derivations in their utmost consequences predict isokinetic behavior for any reaction series, and this prediction is clearly at variance with the facts. Only Ruetschi’s theory makes allowance for nonisokinetic behavior (96), and Thorn first attempted to define the “reaction series” in terms of monotonicity of AS and AH (125, 209). It follows further from pure thermodynamics that a qualitative compensation effect (not exactly a linear dependence) is to be expected either for constant volume or for constant pressure parameters in all cases, when the free energy changes only slightly (2 14). The “reaction series” would thus be defined by “small” differences in reactivity. However, any more definite prediction, whether the isokinetic relationship will hold or not, seems not to be feasible at present. Many workers have offered the opinion that the isokinetic relationship is confined to reactions in condensed phase (6, 122) or, more specially, may be attributed to solvation effects (13, 21, 37, 43, 56, 112, 116, 124, 126-130) which affect both enthalpy and entropy in the same direction. The most developed theories are based on a model of the half-specific quasi-crystalline solvation (129, 130), or of the nonideal conformal solutions (126). Other explanations have been given in terms of vibrational frequencies involving solute and solvent (13, 124), temperature dependence of solvent fluidity in the quasi-crystalline model (40), or changes of enthalpy and entropy to produce a hole in the solvent (87). The most fundamental thermodynamic approach of Rudakov (6) applies to all condensed systems. The actual li?ear relationship is argued to exist between enthalpy (AH) and entropy (AS) of intermolecular interaction, as reflected in an approximately linear relationship between the total enthalpy and entropy. Special attention has been given to hydrophobic interaction (89,90) in water solutions, which makes the isokinetic behavior more pronounced and markedly changes its slope. The most popular theory based on solvation was developed by Hepler and

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O’Hara (134, 135). The total values of A H and AS are divided into internal (AHh,, A s h t ) and external, i.e., solvation, (AH,,,, AS,,, ) terms:

6AG = 6AHi,,, +&AH,,,

+ -T6ASint

- T6ASext.

(70)

It is now assumed that (a) & A s h t can be neglected and that (b) 6AHext and &AS,,, are correlated by an isokinetic relationship with a given flex,. A rough correlation of 6 A H and 6 A S would thus in fact be caused by a much closer correlation of &AH,,, and &AS.If the value of Pext were known or could be estimated, 6AHbt would be obtained from experimental quantities as

6AHint = -RT In k t(T -P,,t)SAS.

(71)

Up to this point, n o objection can be raised to the theory, but the values of flex, near the experimental temperature (134, 135) are suspicious and estimates based on correlation with vibrational frequencies (134) are loaded with still greater statistical defects than is the simple correlation of A H and AS. There probably is no straightforward possibility of estimating flex, : comparison of two similar reaction series (71) or the best fit with respect to the additivity principle (73) lead only to uncertain values, not significantly different from T. Several discussions (71, 73, 78, 11 I , 137-141) in terms of 6AHh, and 6AH,,, seem to be of not much value. Since Pext is supposedly almost equal to T, in fact 6AG values are discussed instead of 6 A H h t . The same conclusion applies to the separation into reaction and hydration contributions (79, 112) corresponding to the internal and external terms: here the explicit assumption /3 = T was made at the beginning (79). The crucial test of all of the theories based on solvation would be the absence of the isokinetic relationship in the gas phase, but the experimental evidence is ambiguous. Rudakov found n o relationship for atomization of simple molecules (6), whereas Ruetschi claimed it for thermal decomposition of alkyl chlorides (96) and Denisov for several radical reactions (107): however, the first series may be too inhomogeneous and the latter ones should be tested with use of better statistics. A comparison of the same reaction series in the gas phase on the one hand and in solution on the other hand would be most desirable, but such data seem not to be available. Among the theories of limited applicability, those of heterogeneous catalysis processes have been most developed (4, 5, 48). They are based on the assumption of many active sites with different activity, the distribution of which may be either random (23) or thermodynamic (27,28,48). Multiple adsorption (46, 47) and tunnel effects (4, 46) also are considered. It seems, however, that there is in principle n o specific feature of isokinetic behavior in heterogeneous catalysis. It is true only that the phenomenon has been discovered in this category and that it can be followed easily because of large possible changes of temperature.

THE ENTHALPY-ENTROPY RELATIONSHIP

463

Other particular theories are confined to diffusion-controlled reactions (109), to the so called cooperative processes (113), in which the reactivity depends on the previous state, or to resistance of semiconductors (102), while those operating with hydrogen bridges (131), steric factors (132), or electrostatic effects (133, 175) are capable of being generalized less or more. To conclude this section, we can state that all of the theories presented hitherto, even when starting from general principles, inevitably embody several assumptions, which in fact represent the heart of the analysis. However, the physical meaning of these assumptions usually is not known, so that no theory is able to predict in which reaction series isokinetic behavior appears and in which it does not. Neither is the structural theory of organic chemistry able to make such a prediction and to define the terms “reaction series” or “similar reactions” or “small structure changes”: it can only afford many examples.

D. Relation to Extrathermodynamic Relationships The term extrathermodynamic relationship has been introduced (2) to denote relations between thermodynamic quantities which do not follow from the fundamental laws and are mostly supported only empirically. With this definition they include the isokinetic relationship (2). Hence, in this section we shall discuss the relationship to that restricted class of extrathermodynamic relationships which correlate free energies with sets of empirical constants and are also called linear free energy relationships (LFER) (9). Well known examples are the Hammett (16, 17) and Taft (12) equations. Equations of this type had been used for a long time for various reaction series without respecting temperature and even for the same series at different temperatures. This was because Hammett (16)-and still later authors (215, 216)-assumed originally that entropy is constant in these reaction series. However, it can be proved as follows that this condition is not necessary (see 18, 19, 136, 195). Let us write a simple LFER in the form of eq. ( 1 7) which implies that structural changes can be expressed by one structural parameter only (a). By expressing log k through activation parameters, it follows that 6 AH - T6AS = -2.303 RT ~ T C J

(72)

If 6AH, 6AS, and a are independent of temperature, it follows that p~ is a linear function of reciprocal temperature, so that eq. (73) holds 6AH - T6AS = -2.303 RuA -2.303 RTuB

(73)

when A and B are arbitrary constants. This equation can hold for arbitrary temperature only when 6AH equals the first and -TGAS the second term on the right-hand side. It follows that 6AH and 6AS are proportional with the proportionality constant 0 = -A/B finally giving eq.(10). It has thus been

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proved that the isokinetic relationship is a necessary condition for a simple LFER to hold. At the heart of the analysis lies the assumption that a single, temperature-independent u acounts for structure variations.* For the theory of LFER's, two consequences follow: (a) The reaction constant p should depend on T according to eq. ( 1 8), and (b) values of A H and AS should obey the pertinent relationship as well as log k. The experimental evidence seems to be in accord with the first postulate (9, 17). Sometimes the simple proportionality to T-' was claimed (124), corresponding t o the isoentropic series but this is only a particular case, of course. Recent exact measurements (196) can be interpreted by eq. (18) as well as by several other simple functions: the reaction chosen was, however, not quite appropriate because of the low degree of correlation. The direct evidence for the second postulate is very scarce (9, 59, 217-219) and seems to be even negative (176, 197): we believe, however, that the main reason is the experimental inaccuracy. Ritchie and Sager ( 1 24) distinguish three types of reaction series according to whether the Hammett equation or the isokinetic relationship is obeyed, or both. The result that the former can be commonly valid without the latter seems to be based on previous incorrect statistical methods and contradicts the theoretical conclusions, Probably both equations are much more frequently valid together than was anticipated. The last case, when the isokinetic relationship holds and the Hammett equation does not, may he quite common, of course, and has a clear meaning. Such a series meets the condition for an extrathermodynamic treatment: when enough experimental material accumulates, it is only necessary to define a new kind of substituent constant. The conclusions reached hitherto apply to simple LFER involving only one variable parameter (2, 120). A more general type can be considered in the form S logk=p,ol + P ~ Q

(74)

where p e p z are temperature-dependent reaction parameters and UI, u2, temperature-independent substituent parameters. Examples of this type are the equations of Yukawa-Tsuno, Taft, Dewar-Grisdale, Swain-Lupton, SwainMosely-Bown, etc.; see (9). By the same argument as in eqs. (72) and (73), we

* An attempt to derive the isokinetic relationship still more generally considering a temperature-dependent u (2) is not quite correct. Equation (72). corresponding to eq. (4), p. 317, of (2), then has a solution o(T, t ) = I f ( 0 +g(E)T-' 1 l d T ) when p = q(T) and f([), g(E) are arbitrary functions of the structural parameter 5 . This solution can hardly have any physical meaning but shows that 6 A H and 6 A S need not necessarily be linearly interrelated unless the assumption is made that u is temperature independent.

THE ENTHALPY-ENTROPY RELATIONSHIP

465

derive that both p1 and p2 must be linear functions of reciprocal temperature: SAH-T6AS= -2.303 R ( ~ l A + ~ z C ) - 2 . 3 0 RT(u~B+u*D) 3

(75)

In this equation, 6AH must equal the first and SAS the second term on the right-hand side so that there is no simple relationship between them. However, the “imaginary” isokinetic temperatures p and P 2 , corresponding to the two interaction mechanisms, can be defined as P1= -A/B and P2 = -C/D.The resulting relation between AH and AS is scattered (2) as shown in Figure 19.

AS

Figure 19. Relation between AH and A S for two interaction mechanisms characterized by the values and p, (schematic example).

The derivation outlined may thus serve to explain such scattered graphs: however, no possibility is offered of estimating P I and P 2 . The situation is complicated by the known fact that the plot of AH versus AS is statistically erroneous. The same objections apply to Leffler’s special case (153) when experimental error is formally treated as an additional interaction mechanism with p2 = Texp . Even in this case, no possibility is given of estimating the real pl. Relations of another kind between LFER and the isokinetic relationship were sought by Lee (165-167), who tried to incorporate both in one extended

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equation. The experimental support, however, suffers from still heavier statistical deficiency than the usual correlations of AH versus AS.

VI. SIGNIFICANCE OF AG, AH, AND A S IN STRUCTURAL CHEMISTRY The knowledge of the isokinetic relationship may assist in treating one fundamental problem of organic structural chemistry: i.e., which experimental quantity should serve as a measure of reactivity and be correlated with theoretical predictions. As mentioned in the introduction, the only significant quantity is the experimentally inaccessible potential energy Ep. It has also been shown-see eqs. (6) and (7)-that only in reactions with a constant entropy can either AG or A H be identified with Ep (16). Such reactions were formerly believed to be rather common (16), and they have even been found recently [e.g., (220, 221)] and postulated theoretically (215, 216). However, the evidence is now quite convincing that in many important reaction series, changes of entropy are important or even play a decisive role in determining reactivity (1, 17, 74-76, 222-224). It has also been shown in the introduction that 6AG and 6AH have the same relative values and the same meaning when the isokinetic relationship holds, even when it is not quite certain that they can well approximate 6Ep. Hence, there is the problem of deciding whether the isokinetic relationship is obeyed or not. According to the analysis of Sec. IV, the decision will seldom be certain: more frequently, the validity of the relationship is only approximate, and a decision can be achieved only to a certain probability. In these common cases, only some theoretical or empirical arguments can be advanced in favor of AG or AH as a measure of reactivity. Most of the theoretical arguments support the statement of Evans and Polanyi (20), who first argued that AG represents the situation at 0°K better than does AH. The main reason is seen in solvent effects. Dewar expressed this meaning in the most radical manner, saying that determination of A H and A S in solution is simply a waste of time (21). Laidler offered similar ideas and stressed that a theory for AG can be more easily developed than for A H (13,225). The approach of Hammett is still more general and not restricted to solvent effects (226). According to Hammett, a reaction that is more complex than it appears to the observer and consists of two parallel independent processes will affect the value of A H more than will AG. Empirical evidence seems also to support the preference for AG. Ingold based all of the structure-reactivity discussions in his famous book on AG values and believed that this choice is in accord with overall experience, at least as long as very small differences are disregarded (22). Values of AG usually correlate better with quantum chemical indices (199) and with empirical reactivity

THE ENTHALPY-ENTROPY RELATIONSHIP

467

constants (176, 197, 198): on the other hand, better correlations with AH also have been claimed in some instances (2 18,219), and this quantity is preferred in certain theoretical conceptions (7), particularly when related to the computed electrostatic energy (227) or to the sum of electronic substituent effects and the repulsion part of steric effects (12, 132). The empirical arguments based on correlation with a kind of reactivity parameter have a common weakness: i.e., they do not guarantee that the appropriate kind of constant has been chosen. To make the whole procedure free from a fixed scale of constants, the following test was advanced by the reviewer (188), and a similar approach was used by other authors (71, 1 1 I).,Let us consider two reaction series so similar in nature that any theoretical prediction must yield the same sequence of reactivity for both. When one compares their A H values on the one hand and their AG values on the other, one can decide which correlation is closer and hence which quantity is more suitable for structure-reactivity studies. To a certain degree, the result of this comparison can be foreseen. When the isokinetic relationship is strictly obeyed for both series, the same degree of correlation is obtained for both quantities. When it is not obeyed, no correlation between AG values can in principle exist: should it appear by chance at any temperature, it must break down when temperature is changed. The correlation between AH values is principally possible in this case but no experimental evidence seems to be known. Most frequently, the isokinetic relationship is obeyed in both series only approximately, and it cannot be predicted generally whether the correlation is closer between AH values or between AG values. Only when the deviations are caused by experimental errors (or by any other random factor) can it be proved that the correlation between AG values must be closer. An example is given in Figure 20 (1 SS), concerning alkaline hydrolysis of substituted benzoic acid methyl esters and ethyl esters (228). In the first quadrant, AGS values, and in the third one, E*(AHS) values are plotted against each other: the main difference is the larger experimental error in the latter. The second and fourth quadrants represent the isokinetic relationships for the two reaction series, respectively, by a plot of AH versus AG according to eq. (13)-a statistically incorrect plot in this case. There is quite another situation in the second example: reaction of aldehydes and ketones with hydroxylamine on the one hand and with thiosemicarbazide on the other hand (229). The correlation between free activation energies (2, 188) is still quite close (Figure 21), but the experimental errors in AH$ are so large that no correlation is perceptible. The main difference between the two examples lies in the narrower temperature interval in the latter: this factor is of primary importance, in general. However, it can be shown that improving the accuracy of measurement and enlarging the temperature interval also improves the averaged rate constant (AG) so that it still remains more accurate than AH.

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Figure 20. Relations between AG and between E* values for two related reactions: alkaline hydrolysis of substituted methyl and ethyl benzoates (188,228).

When the isokinetic relationship holds, it is useless to discuss separately the values of A H and A S in addition to AG. In fact, it has happened many times that it was the experimental errors in A H and A S which were discussed. To avoid this possibility, it has been suggested (163) that isokinetic enthalpy AHi, and isokinetic entropy ASis be defined as values computed with the isokinetic constraint. The values of AI-&i0 are directly connected to the slopes b of isokinetic lines in eqs. (39), (39a), (49), (54) and (59): e.g., for = -2.303 R bi - RT

(76)

In the expression for AHyso , the term -RT drops out. The values of ASiso are then obtained from AHiso and AG. The relationship of isokinetic and unconstrained activation parameters is shown in Figure 22 (see Table I). The computed values (57) of A H and AS are shown together with their estimated errors, which are mutually dependent. The points can thus only move along a

THE ENTHALPY-ENTROPY RELATIONSHIP

469

Figure 21. The same relation as in Figure 20 for reaction of various carbonyl compounds with hydroxylamine and thiosemicarbazide (188, 229).

given line with the error slope. The point of intersection of this given line (prolonged if necessary) with the isokinetic line determines AHiso and ASiso. These values may differ distinctly from the unconstrained A H and AS, although the difference will only seldom exceed the standard error, when the isokinetic relationship is valid. In the isoenthalpic and isoentropic reaction series, the isoenthalpic and isoentropic activation parameters, respectively, may be defined as a special case of isokinetic values. Values of this kind are certainly more reliable than the usual ones in all cases when the isokinetic behavior has been proved, or, better, when it cannot be rejected. In dubious cases, when it cannot be disproved with any reliability but yet would cause a reduction of the overall accuracy, we recommend the calculation of both isokinetic and unconstrained parameters. In

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470

AH' kul /

/

-2

-1

-0

-I

I

I

10

20

bS'e.u.

Figure 22. Representation of isokinetic (0 ) and unconstrained parameters, the same reaction series (57) as in Figure 13.

(0 )

activation

the remaining cases, the preference of AG or A H is still open t o a certain extent: an experimental solution sketched in Figures 20 and 21 would require more material than is available at present. VII. MORE GENERAL RELATIONS A. Temperature-Variable Activation Parameters

The whole analysis given hitherto has been conditioned by the strict validity of the Arrhenius equation. In fact, this equation is satisfactory for most organic work (191, 230), or for solution reactions in general, the main reason being the limited temperature range available in solution and a relatively low accuracy with complex reactions. What is still more important, the accuracy of the Arrhenius equation is usually completely sufficient when compared with the low

THE ENTHALPY-ENTROPY RELATIONSHIP

471

accuracy of the isokinetic relationship. Even so, more accurate measurements have accumulated in recent years, allowing or requiring a more sophisticated treatment (79-81, 168, 169,230-234). Several types of extended equations were considered (79, 232, 235): the most fundamental analysis has been done by Clarke and Glew (235), while Wold tested some simpler forms suitable for applications in organic chemistry (232, 233). Considering the approximate validity of the Arrhenius equation, we may write a general temperature function in the form log k = A + BT-’

+ Cf(T)

(77) where the third term represents a correction of less significance. We now stay before the problem to define “isokinetic behavior” (in a generalized sense) for such a system. The most reasonable postulate seems to be (236) that the ratio of reactivity (i.e., the relative distance among the lines logk versus T) is not changed with temperature and can be expressed as

This condition excludes any crossing of lines, of course, but does not exclude any point of intersection if it is common to all lines (Figure 23). Equation (77) meets the condition in eq. (78) when the parameters A, B, C are mutually bound by linear relations, transforming it into the form log ki = A + B& + ,$iT-’ t (C t D&)f(T) where

ti is the

(79)

generalized structure parameter characterizing the ith reaction

Figure 23. Schematic representation of generalized isokinetic behavior with temperature-dependent activation parameters.

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412

within the series and A-D are constants, common to the whole series. It can also be shown that 6AH and 6AS at a given temperature obey the relation =PT@WT

(80)

where PT is the generalized isokinetic temperature (Figure 23).* It is a function of T whose form depends on the function f(T) in eq. (79). A temperaturedependent p was theoretically considered several times (96, 123, 130); and the idea that it is shifted in the same direction as T and consequently lies always outside the experimental interval (149) is particularly attractive, but has not been proved. A similar relationship between AS and AC,, the heat capacity of activation (or reaction), follows also from eq. (79): ( 6 A c p ) ~= YT(SAS)T

(81)

Such relationships were in fact found empirically (168, 169, 231): however, they should be confirmed by use of correct statistics. The whole treatment with temperature-dependent parameters has to be completed with appropriate statistical methods and tested on selected reactivity data (236) before one can judge whether it is worth the effort. Few data available at present fulfil the high demands on accuracy and extent. A special case of the isokinetic temperature is still to be mentioned, confined to a single reaction only, not strictly obeying the Arrhenius law (53). Temperature itself thus represents the variable factor, and the relation of AH and AS may be written (AWT = p ( A s ) ~t h o

(82)

However, it can be proved simply that this equation cannot hold. By substituting the thermodynamic definitions of AH and A S into eq. (82), we get

a In k (T2 -0T) aT

=

h In k to R

(83)

The only solution of this differential equation is with both AH and AS constant (149). On the other hand, it was argued that a qualitative compensation effect must exist in this case since AH and AS change with temperature in the same direction (214).

B. Relationships between Arbitrary Quantities The utmost generalization of the isokinetic relationship is the so called isoparametrical relationship (1 7 l), considering the dependence of a given

* Christiansen (123) supposed f(T) in a special form eCYT/T.When now A, B, and CY are constant throughout the series and only C is variable, a linear relationship between A HT and A ST arises. However, the assumptions seem rather unrealistic.

THE ENTHALPY-ENTROPY RELATIONSHIP

473

quantity (y) on two arbitrary parameters (t Ez). When the relationship is linear with respect to both parameters, the general form of the overall function reads

It follows that for a special value of one parameter, the observed value of y is independent of the second parameter. This happens at t l = -a2/a12 or E2 = -aJalz: any of these values determines y = a. - al a2 /al2, the so called isoparametrical point. The argument can evidently be extended t o more than two independently variable parameters. Experimental evidence is scarce. In the field of extrathermodynamic relationships, i.e., when E l and E2 are kinds of CJ constants, eq. (84)was derived by Miller (237) and the isoparametrical point was called the isokinetic point (170). Most of the available examples originate from this area (9), but it is difficult to attribute to the isoparametrical point a definite value and even to obtain a significant proof that alz is different from zero (9, 170). It can happen-probably still more frequently than with the isokinetic temperature-that it is merely a product of extrapolation without any immediate physical meaning. VIII. CONCLUDING REMARKS The task of the foregoing analysis was to demonstrate the general significance of the isokinetic relationship and particularly the need for correct statistical methods in this area. Nowadays, means are available for deciding whether the relationship is obeyed or not, for computing 0, for estimating its confidence interval, etc. With respect to the large uncertainty inherent in 0, the former result seems to be more important. In the writer’s opinion, each reaction series of theoretical importance should be examined carefully and the isokinetic and nonisokinetic ones clearly distinguished, since the interpretation of reactivity must be different in both. A straightforward discussion in temperatureindependent terms is in fact allowed only in the former cases. In the latter cases, the discussion based on AG values may be more convenient than one on AH. The necessity of the statistical approach has to be stressed once more. Any statement in this topic has a definitely statistical character and is valid only with a certain probability and in certain range of validity, limited as to the structural conditions and as to the temperature region. In fact, all chemical conceptions can break down when the temperature is changed too much. The isokinetic relationship, when significantly proved, can help in defining the term “reaction series”: it can be considered a necessary but not sufficient condition of a common reaction mechanism and in any case is a necessary presumption for any linear free energy relationship. Hence, it does not at all detract from kinetic measurements at different temperatures: on the contrary, it gives them still more importance.

P

P

I .

10. Solvolysis of ethyl benzoate (240) 11. Solvolysis of isopropyl benzenesulfonate (241)

Kinetics 7. Proton transfer from nitromethane to carboxylic anions (156) 8. Reaction of triarylcarbonium ions with OH- (186, 187) 9. Reaction of aryl cyclopropanecarboxylic acids with DDM (239) solvent solvent

25-45 1048 38 59

7 17

.005 .010

.012

15-20

33

subst. 8

5

subst.

.009

19

struct. 65

.035 .032

.007 .004 .002 .023

.096

.003

.011

so0

50

40 40

40 20 15 35

65

45-50

45-55

AT^

.024

61

36 56

36 20 16 24

60

64

44

ZmiC

20-30

9 14

4 4 4 6

struct.

struct.

12

subst.

subst.

6

subst.

(82) 6. Reaction of 1,ldinitrocompounds with CH,O (57)

4

lb

subst.

Variable factora

5. Ionization of substituted anisalanilines

4. Ionization of substituted cyanoacetic acids (79-81)

Equilibria 1. Ionization of meta-substituted phenols (68) 2. Ionization of 3,Sdisubstituted anilines (73) 3. Ionization of polynitroanilines (238)

Reaction

.25+ .25!+ .25l+ 9.005.005-

.lo+ .01 I .016. .016: .016' .026 .018

.005-

no+ .005-

no+ . >.2S1+ 9.0059.005<.005.lo+

9.005-

>.25+ .25'+

Previous estimates

p p p p

= 328 (81) = 322 (81) = 326 (81) = 1 2 or 183 (82)

(573) (-135)

= p=0

-1920 (239)

(636) p = 102 'r' = .947 (156) 335 p = 331 (187)

491 (1880) p = 690 (57)

(259) (194) (267) 91

m

-1740

-52 p = -69 (68) 0 (-961) p = 80 f 100 (73)

Validity of the IKRg p"Kh

.039

.03 1 .061

.089 .098' .027 .021 .009 .034

.012. .013' .007

S"

Some Reaction Series Tested as to Their Isokinetic Behavior

TABLE I11

VI

?i

(117) (1016) p = 740 (246)

.01’-

.016 .048 .047 .034

.005 .043 .027

15-25 10 10 50-110 3045

43 46 48 32 56

11 23 24 6 10

subst. struct. catalyst pH

.25+ .lo+

i.

4.005-

-659

.lo+

.025. .035’ .017

.020

15-20

26

6

subst.

-

-

no relationship

-581 no relationship (1) (714) 693 p 694 (4,189) 436 p = 285 (247)

-

518

p = 417 (244)

.05+

.052

.033

1040

40

13

subst.

0

.05+

.025

.018

63

13

subst.

15-20

2010 629 p = 610 f 10 (243)

no+ .05+

.004

,035 .005

10-35 20

.036

63 70

14 14

subst. subst.

Small variances of structure are denoted as “substituent”, larger ones as “structure”. Number of reactions. Number of all data. Temperature range for one reaction; if not unique, limits are given. Standard deviation from unconstrained lines, see eqs. (41), (55); it serves mostly as estimate of the experimental accuracy. Standard deviation from isokinetic lines, see eqs. (40), (53); it expresses accuracy of the isokinetic relationship. The confidence level is given at which the isokinetic relationship is rejected: when Q! 2 .05 the relationship is denoted as valid (+). When so < so,, the relationship cannot be rejected at any a . hThe isokinetic temperature: for nonvalid relationships, it is given in parentheses. The symbols 0 and denote isoenthalpic and isoentropic series, respectively. Related to the isokinetic temperature given in the appropriate column.

a

12. Solvolysis of benzhydryl bromides (242) 13. Hydrolysis of 2,2dinitropropylanilines (243) 14. Hydrolysis of substituted diazoacetophenones (190) 15. Hydrolysis of substituted 9-chloroacridines (244) 16. Substitution of chloro- and bromonaphthalenes with piperidine (245) 17. Coupling of aryldiazonium salts with Bronner acid (246) 18. Lossen rearrangement of dihydroxamic acids (208) 19. Decomposition of formic acid (4,189) 20. Chymotrypsin hydrolysis of ATEE (247)

416

OTTO EXNER

Further information obtained from the isokinetic relationship concerns the classification of reaction series, especially the division into those with increasing and decreasing selectivity according to the value of p. It is, however, still the task of future theory to give this classification a physical meaning. On the other hand, the exact numerical value of /3 should not be given too much significance, and in fact, many misunderstandings in the past arose from unnecessarily stressing this point of view. The first problem in this area is a revision of the older results obtained by incorrect statistics and concerns particularly the isokinetic relationships in physical properties. The next task of the theory is predicting the range of validity: i.e., to define the term “reaction series”. Probably a larger amount of exact data will be necessary for this aim than is available today.

IX. APPENDIX Up to now (1971) only a limited number of reaction series have been completely worked out in our laboratories along the lines outlined in Sec. IV. In fact, there are rather few examples in the literature with a sufficient number of data, accuracy, and temperature range to be worth a thorough statistical treatment. Hence, the examples collected in Table I11 are mostly from recent experimental work and the previous ones (1) have been reexamined. When evaluating the results, the main attention should be paid to the question as to whether or not the isokinetic relationship holds: i.e., to the comparison of standard deviations of so and soo . The isokinetic temperature /3 is viewed as a mere formal quantity and is given no confidence interval. Comparison with previous treatments is mostly restricted to this value, which has generally and improperly been given too much atention.

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48 1

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482

OTTO EXNER

218. Slootmakers, P. J., R. Roosen, and J. Verhulst, Bull. SOC. Chim. Belges, 71, 446 ( 1962). 219. Dickinson, J. D., and C. Eaborn, J. Chem. Soc., 1959, 3036. 220. Bodor, N., and A. Kovendi,Rev. Roum. Chim., 11, 413 (1966). 221. Ryan, J. J., and A. A. Humffray, J. Chem. Soc. B, 1967, 1300. 222. Boyd, R. H., and C.-H. Wang, J. Am. Chem. Soc., 87,430 (1965). 223. Niirnberg, H. W., H. W. Diirbeck, and G. Wolff, Z . Phys. Chem. (Frankfurt), 52, 144 (1967). 224. Kurz, J. L., and J. M. Farrar, J. Am. Chem. Soc., 91, 6057 (1969). 225. Laidler, K. J., Suomen Kemistilehti, A , 33, 44 (1960). 226. Hammett, L. P., Symposium on Linear Free Energy Correlations, U.S. Army Research Office, Durham, North Carolina, 1964, p. 77. 227. Hiimbelin, R.,Chimia (Switz.). 20, 151 (1966). 228. Tommila, E., Ann. Acad. Sci. Fennicae, A57. 13 (1941). 229. Fiarman, I. D., and J. D. Gettler, J. Am. Chern. SOC.,84, 961 (1962). 230. Hulett, J. R., Quart. Rev., 18, 227 (1964). 231. Robertson, R. E., and J. M. W. Scott, J. Chem. Soc.. 1961, 1596. 232. Wold, S., Acta Chem. Scand., 24, 2321 (1970). 233. Wold, S., J. Phys. Chem., 76, 369 (1972). 234. Marshall, R. M., and J. H. Purnell, J. Chem. Soc., A , 1968, 2301. 235. Clarke, E. C. W., and D. N. Glew, Trans. Faraday Soc., 62, 539 (1966). 236. Wold, S., and 0. Exner, Chem. Scripta, 3, 5 (1973). 237. Miller, S. I.,J. A m . Chem. Soc., 81, 101 (1959). 238. Johnson, C. D., A. R. Katritzky, and S. A. Shapiro, J. Am. Chem. Soc., 91, 6654 (1969). 239. Kostikov, R. R., N. P. Bobko, and 1. A. Dyakonov, Reakts, Sposobnost Org. Soedin. (Tartu), 8,97 (1971). 240. Tommila, E., A. Nurro, R. MurBn, S. Merenheimo, and E. Vuorinen, Suornen KemistilehtiB, 32, 115 (1959). 241. Tommila, E.,ActaChem. Scand., 9, 975 (1955). 242. Mindl, J., P. Pivonka,and M. Ve&kh,Coll. Czech. Chem. Commun., 37, 2568 (1972). 243. Gidaspov, B. V., P. A. Ivanov, Yu. A. Povarov, and V. F. Selivanov, Reakts. Sposobnost Org. Soedin. (Tartu), 8, 49 (1971). 244. Ledbchowski, A,, RocznikiChem., 41, 717 (1967).; 42, 445, 595 (1968). 245. Simonetta, M., and P. Beltrame, Gazz. Chim. Ital., 88, 769 (1958). 246. Rozhdestventskaya, L. M., I. L. Bagal, and B. A. Porai-Koshits, Reakts. Sposobnost Org. Soedin. (Tartu)?6, 114 (1969). 247. Lumry, R., and S . Rajender, J. Phys. Chem., 75, 1387 (1971).

Author Index

Aalenberg, W. I., 331(13), 333(13), 360 (13,376 Abell,P. I., 110(137), 121, 184, 185 Adams, 0. W., 335(55), 377 Agtarap,A., 215-216(40), 319 Alcais, P., 109(91), I 8 4 Alderfer, J . L., 387(41), 4 0 9 Alfrey, T. Jr., 121, 184 Ali, M. A., 359( 130), 379 Allen, G., 215(39),319 Allen, L. C., 272-273(163,165), 274(163), 323 Allerhand, A., 157(210), 159,187 Alt, H., 168(235), 187 Altieri, L., 17 Altschal, H., 9 Amos, T., 359(124), 378 Anderson, H. M., 17 Anderson, K. K., 14(10), 38-42(10), 49(10), 55(10), 79 Andre, E., 212(22) Andrews, L. J., 198(82), 184 Andrussoco, K., 61,95(64), 136(64), 147 (64), 183 Angelelli, J. M., 2 1( 1 l ) , 79 Antell, K., 417(42), 419(139), 426(42), 4 7 7 Apeloig, Y., 262(137), 277-278(173), 288 (173,185), 305(173), 322-324 Arenberg, C. A., 17 Arens, J. F., 222(71), 320 Armand, J., 145(169), 186 Amett, E. M., 33,410(175), 427(192,193), 457( 175),462( 139), 463(175), 480,481 Atherton, N. M., 349(98), 378 Atidia, M., 263(144), 322 Avarboch,H. S., 213(26),319 Avedikian, L., 419(138), 453(138), 462 (1 38), 480 Awad, E. S., 398,409 Axenrod, T., 17 Aylward, J. B., 314(215), 325 Baba, H., 90(42), 183 Baddeley, G., 17 Badger, B., 368( 162,166), 369( 162,164), 379 Baeyer, A., 210(16), 318 Bagal, L. I., 417(58), 423(58), 475(246), 478, 482 Bahn, C. A., 275-276(170), 283-284(170), 303(170), 323 Bailey, A. S., 111( 148), 185

Bailey, W. C., 83,94,95(16) Baird, N. C., 345-346(82), 378 Baker, A. D., 351-352(103), 365(103), 378 Baker, C., 351-352(103), 365(103), 378 Baker, F. W., 5 ( 8 ) , 79 Baker, L. E., 168(225), 187 Balabanov, E. I., 418(105), 479 Balandin, A. A., 417(45), 420(45), 4 7 7 Baldwin, J. E., 264(148), 322 Baliga, B. T., 481 Balk, P., 330(6), 359(149), 360(6), 376, 3 79 Ballentine, A. R., 239(93), 253(93), 321 Balsohn,M.,210(15),318 Bamford, Ch. H., 125, 185 Banewicz, J. J., 159,187 Banwell,C. N.,91(53),93,95(53), 101(53), I83 Barbier, G., 109(91), 184, 212(24), 319 Barclay, I. M., 418(86), 478 Barfknecht, G. W., 259-261(126), 322 Barnard, J., 334(37), 377 Barsh, M. K., 426(198), 481 Basila, M. R., 90(46), 183 Bassin, M., 417(55), 478 Bassler, T., 258(124), 264,299(145), 310, 3 12(2 lo), 322, 325 Baudet, J., 359(129), 379 Bauer, R . J., 388, 389(50), 409 Baumgartner, P., 328(3), 376 Baxendale, J. H., 333(22), 376 Beach, J. Y., 243(106), 321 Beard, C. D., 254(108), 255(108,112), 321 Becher, P., 417-418(40), 461(40), 477 Beck, F., 313(214), 325 Becker, E. D., 17 Becker, E. I., 9 Becker, L. W., 161(219), 187 Beckett, M. C., 6,9,29(11) Beek, L. K. v., 86, 183 Beguin, C., 9 Behrman, E. J., 419(145), 428(145), 480 Bekkum, H. v., 2(2e,7), 3(2e), 20(2e), 44 50(2e),m Bell, R . B., 213(27), 319 Bell, R. P., 109(96), 147(174,186), 184, 186, 418(85), 478, 481 Belleau, B., 385, 397,408 Beltrame, P., 418( 117), 456(117), 475 (245), 479, 482 Benbrook, C. H., 33 Benfey, 0. T., 261(133), 332

(a,

483

4 84

AUTHOR

Benghist, I., 9 Benkeser. R . A . , 9 , 16,29, 191 Benkovic, P. A., 407(106), 410 Benkovic, S. J . , 406(104,105), 407(105, 106). 410

Bennema, P., 360( 154), 379 Bennett, J . E., 330(8), 376 Bent, R . L., 168(237), 187 Benttude, W. G., 426(192,193), 481 Berinek, V., 419(164), 425(164), 448-450 (164), 452(164), 457(164), 480 Berchet, G. J . , 221(61), 320 Bergel’son, L. D., 217(44), 319 Bergman, R . G., 258(122), 264,265-266 (149). 269(146,149), 274(122), 278,279 (122,174,175b).280(175b), 291(190), 299(146,149), 305(175b), 307(190), 311, 313(212), 318, 322-325 Berkheimer, H. E., 33 Berlin, A. A., 418(105), 479 Berliner, E., 6,9,29(11), 191 Bernatek, E., 120(101,102,105),184 Bertheuil, G., 359(128), 379 Berthier, G., 334(26), 359(120,129), 364 (35), 376-379 Bertrand, M.,221(63), 237,238(90,98), 239,242,251(89), 253(92), 265,299 (150), 320-321 Bethel, D., 264(147), 322 Bevan, J., 17 Beveridge, D . L., 346-347(85), 355(85,100), 3 78 Bhaskar, K. R., 138,185 Bianchini, J . P., 221(68), 228(68), 320 Bieber, P., 185 Bielski, B. H. J., 359-360(136), 379 Bienvenue-Goetz, E., 108, 109(91), 184 Biggs,A. I., 16, 29,417(61), 478 Biilmann, E., 168(234), 187 Bineel. W.. 359(126). 379 Binks,~l.H., iiO(i2’ij, 124(123), 185 Birchall, T., 17 Birktoft, J. J., 384(20), 396(20), . . 408 Birss, F. W., 334(33), 376 Bitterwolf,T. E., 426(196), 464(196), 481 Bixon, R., 323 Blackadder, D . A., 418-419(115,116),428 (115,116), 433(115,116), 436(115,116), 456(115,116), 458,461(116), 479 Blackledge, J., 380 Blagdon, D., 26, 79 Blake, C. C. F., 384(21), 408 Bloomers, E. A., 6(8b), 9,29(11) Bloomfield, J. J., 9, 23 Bloor, J . E., 110(126), 125, 185 Blow, D. M., 384, 385, 396(20,23), 397, 398-399(23), 402,408 Bly, R. S., 239, 240(94), 241, 251(94,95), 253(93), 321 Boaz, H., 405(91), 410 Bobko, N. P., 474(239), 482 Bocker, S., 229(78), 231(78), 245-246(78), 274(167), 275-276(170), 283-284(170), 303(170), 320, 323

INDEX Bock, H., 168(235), 187 Bockris, J. O’M.,169(244), 187 Bodor, N., 482 Bolton, P. D.,417(67-73), 419(71,73), 421 (69,71), 433(69), 462(71,73), 478 Bolton, R., 109(94), 184 Bond, G. C., 413(5), 417(5), 418, 425(5), 456-458(5), 461-462(5), 476 Boozer, C. E., 2 9 4 , 3 2 4 Bonelli, R. A., 2 3 Bopp, R . J., 109(98), 184 Borders, A. M.,9 Bordwell, F. G., 6, 9, 16, 17, 29, 41(21), 79 Boswell, C. J., 308(203), 309(204), 310 (203.204). 312(203,204), 324 Bott, R . W., 17,210, 211,214(36), 218, 219(51), 220(52), 224(17), 227(51,52), 257(120), 319, 320, 322 Bottei, R. S., 152(207), 187 Bouis, M., 22 1(60), 320 Boutan, P. J., 16, 17, 23, 29(7), 41(21), 79 Bowden, K., 59(36), 80, 94,95(59,69), 97, 100-101(59,69), 105, 156,183, 187 Boyd, R. H., 369(168), 466(222), 380, 482 Boyle, Jr., W. J., 17 BOyntOn, W.A., 309-310(204), 312(204),

324 Bradley, R. D., 17 Bramley, A., 159,187 Branch, G. E. K., 33 Brand, J . C., 152(199), 186, 355(112),378 Brandsma, L., 222(71), 320 Bren, V. A., 417(82), 478 Breslow, R., 264(147), 322 Brewer, G. A., 405(91), 410 Brieax, J. A., 1 7 , 2 3 Briegleb, G., 108(81), 184 Bright, R . D., 9,437-438(208), 446(208), 481 Brion, H . , 359(121), 378 Brittain, E. F., 419(169), 480 Broekbhurst, B., 368( 162,166), 369( 162, 164), 379 Broekway, L. O., 243(106), 321 Bronsted, J . N., 147(185), 186 Broom, A. D., 387(40), 409 Broomhead, J. A., 418(110), 479 Br0wn.A. C. R., 110(126), 125,185 Brown, C., 240(97), 321 Brown, D. F.,9 Brown, D. H., 9 Brown, H. C., 2(2c,d,7), 6(la), 29(1), 31, 33, 44(2), 50(2), 61(6), 78, 79, 82(4), 85 (4), 109(100), 112-116(4), 1.82, 184, 259 (1 25), 29 1( 189), 322, 324 Brown, R. F., 418(118,119),419(119), 420 (118,119),428(119), 433(118,119), 436 (1 18,119), 456(118,119), 457(119), 479 Browne, M.W., 277(171),323 Brownell, R. M., 147(172), 186 Brownlee, K. A., 85(30), 182 Brownlee, R. T. C., 21(11), 24, 26(14), 39 (19), 40-41(14), 79 Brugman, C. J. M., 357(117), 378

AUTHOR INDEX Bruice, T. C., 421(173), 456(173), 480 Brundle, C. R.,334, 35 1-352(103), 355(48), 365(103), 377,378 Bruning, I., 111(151), 185 Bryson, T.A., 235(84), 249(84), 320 Buchs, A., 90(41), 183 Buddenbaum, W.E.,292(194), 295(194), 324 Buenker, R. J., 334,377 Buhs, R. P.,405(90), 410 Bunnell, C. A.,223(73), 320 Bunnett, J. F.,48(26), 415(14), 427,458 (14),477 Buraway, A., 295(199), Burighel, A., 287(184), 324 Burke, J. J., 419(139), 426(192), 462(139), 480,481 Burkhart, E. D., 124,185 Burkhardt, G.N., 17 Burnelle, L., 334(38), 335(50), 377 Burnett, G.M., 110(138), 185 Buschow, K. H.J., 360(155), 379 Bushick, R. D.,33,421(175), 457(175), 463(175), 480 Butler, J. A. V., 418(86,92), 478,479 Butler, L. G.,384( 19), 408 Buss, V., 264(148),322 Busz, B. P.,90(41), 183 Bystrov, V. F.,5(8), 78 Cadet, C., 334,377 Caldin, E. F., 425(191),481 Caldow, G.L., 157,187 Canady, W.J., 417(63,64), 453(63,64), 456 (63,64),478 Capato, A. J., 122, 124,185 Cappozzi, G.,284(179,180), 285(181), 286 ( 181,183), 287( 183), 324 Caputo, J. A.,23 Cardew, M.H.,418(101), 479 Carey, L. A.,255( 1 lo), 321 Carlson, R. L., 138,141(159), 185 Carothers, W. H.,221(61), 320 &sky, P., 333(17), 338(58-61). 340(58), 341(58,64,68), 343(59,76), 344(61), 346 (68), 354(68,113), 355(113), 356(61), 358(118), 359(11,17,53,58,59,60,142, 143), 360(11,59,143), 361(59,68), 362 (59), 367(113), 368(118), 372(175), 374 (68), 375(113), 376-380 Caserio, M. C., 107(79), 184 Casey, C., 215(39,40), 216(40), 319 Cassebaum, H.,169(243), 187 Cassidy, H.G., 168(229), 187 Castro, A.J., 17 EermBk, V., 353( 104), 378 Chadwick, J., 17 Chaiet, L.,405(90), 410 Chambers, V. C., 243(104), 321 Chandross, E. A., 373(176,179), 380 Chang, J., 373(180), 380 Chao, T.S.,417(54), 478 Chapman,N. B.,9,59(36),80, 414(9),426 (9),464(9), 477

485

Charman, H. B., 154(206), 187 Charton, B. I., 59(36), 80, 98(72), 99(73), 138, 140(73), 144, 145(73), 146, 149 (190), 160(220), 168(73), 168-169(73), 184,186, 187, 190 Charton, M., 2(2n), 44(2), 50(2), 59(34-36), 62,78, 80, 82(10), 83,85,87,88(37,38, 47),90,91(48),94,95(60), 98(72),99, 100(60), 106(75), 108, 109(84), 1 1 1 (142), 114-115(10), 117(92), 122, 124, 126, 127, 131, 133(47), 135, 136(48), 138,140(73), 144,145(73), 146,147(29, 170), 149(10,190,191),150, 151, 156, 157,160(220), 161(19,215), 163, 164, 167, 168(73), 169(15,73), 176,177, 178 (lo), 179(19,29), 182-188,190, 191 Chaudhuri, J. S.,367(160), 379 Chen,A., 152(197), 154(197), 155,186 Chen,D. T.Y.,417(66), 456(66), 478 Cherkashin, M. I., 418(105), 479 Chevalier, R., 385, 397,408 ChOlOd, M. S., 110-111(140), 126,185 Christensen, J. J., 417(74-77), 421(74-77), 453(74-77), 454(75), 456(74-77).478 Christenssen, F., 120(105) Christiansen, J. A., 417,418(123), 428 (123), 477.479 Chuang, L. Y.Y., 110(133), 185 Ciampolini, M.,417(60), 478 Cfiek, J., 331(14),376 Clancy, D. J., 90(46), 183 Clark, P. A., 349(97), 378 Clarke, E.C. W., 471 Clarke, T.C., 279-280(175b), 291(190), 305(175b), 307(190), 323, 324 Claxton, T.A., 334(39-42),377 Cleland, W.W.,383, 393(69), 408,409 Clementi, E., 335(52), 377 Clippinger, E.,261(133), 271(155), 322, 323 Closson, W. D., 234(83), 249(83), 320 Cochran, E. L., 83,182 Cohen, J., 385(27), 408 Cohen, R. B., 418(131), 428(131), 463 (131),479 Cohen, S. G., 396,401,402(82),409,410 Cohn, M.,385, 393-394(71), 396,408,409 Cohn, M. L., 256(115), 321 Collman, J. P., 257(119), 322 Colter, A. K., 24,33, 34 Conaut, I. B., 168(226,227), 187 Constable, F. H.,417,460-462(23),477 Coop, I. E.,243(106), 321 Cooper, G.C., 9, 16,29 Cooper, J. T.,379 Copeland, B. K.W., 421(174), 480 Cordes, E. H.,383(4), 408 Cornu, G.,152(202), 186 Cotter, J. L., 369(169),380 Cottrell, T. L.,367(159), 379 Crable, G.F.,90(40), 183 Craig, D.P., 41(21), 79 Cram, D. J., 277(171), 323 Cramer, F.,91(52), 183, 389(54), 409

4 86

AUTHOR INDEX

Cramer, R., 207(3), 318 Cramer, R. E., 349(96), 378 Crandall, J. K., 223(73), 320 Crecely, K. M., 101(80), 107(80), 184 Crecely, R. W., 101(80), 107(80), I 8 4 Cremer, E., 413(4), 416(4), 417(4,25,47), 418, 419(4), 425(189,4), 428(4), 456(4), 457(4,27,189), 458(4), 461-462(4,27,47), 4 76, 4 77, 48 1 Cremonini, B., 191 Crimmins, F. T., 419(137), 428(137), 453 (137), 462(137), 480 Cross, P. C., 351(102), 364-365(102), 378 Crossley, M. L., 33 Crow, E. L., 85(30), 183 Cseh, G . , 257(121), 259,297(121), 322 Csiimadia. I. G.. 272-273(164), 323 C u b , D.’Y., 243(102), 255-256(113), 297 (113),321 Cvetanovic, R. J., 120, 184 Dahl, L. F., 404,410 Damrauer, R., 321 Darienko, N. I., 418(106), 479 Davis, F. A., 85(30) Davis, G. T., 14(10), 29(10), 38-42(10), 49 (lo), 5 5 ( 1 0 ) , 79 Davis, M. M., 6, 61(1) Davis, 0. C. M., 17 Day, A. C., 257(118), 322 Dayal, S. K., 17, 2 4 Dean, E. B., 31(17), 33, 79 DeBoer, C. E., 191 DeBoer, E., 362(157), 379 DeBoer, J . L., 347(90), 378 De Bruijn, S., 359(149), 379 De Bruin, K. E., 213-214(28), 224(28), 319 Decius, J . C., 351(102), 364-365(102), 378 DeFazio, C. A., 419(142), 428(142), 431432(142), 480 DeHeer, J., 83,182 DelBene, J . E., 335, 354, 355, 357, 358, 377, 378 Demjanoff, N., 220(55), 320 Denisov, E. T., 418(107), 460(107). 462, 4 79 Dennis, E. A., 385(27), 408 Deno,N. C., 33, 39(19),264(147), 79, 322 Derocque, J., 2 5 1(86), 321 Desai, A. G . , 418(111), 462(111),479 Dessloch, J. C., 168(237), 187 Dessy, R. E., 152(197), 154(197), 155,186 Devaquet, A., 374(181), 380 Dewar, M. J . S., 130, 131, 177, 185. 272 ( 1 60,163), 27 3-274( 1 6 3). 2 7 7 ( 172), 323, 334, 336, 338(34), 341(65), 344(34,80), 345-346(82,83), 356(34), 376-378, 417 (21), 418(21,128), 428(128), 458(21), 461(21,128),477, 479 DeWolfe, R. H., 95(71), 183, 295(198), 324 Dickinson, J . D., 464(219), 482 Dickson, J . D., 48(26), 79 Dieleman, J . , 360(155), 379 Diffenbach, R. A., 33

Dijkstra,A. J., 110(135,136), 185 DiDuv. F. J.. 23 Dippi; J. G.;9, 61(7) Distler, D., 359(135), 379 Dixon, P. S., llO(131) Dobosh, P. A,, 346-347(85), 350(85,100), 3 78 Dolman, D., 17 Dondon, M. L., 95(62), 183 Doscher, M., 384(17), 408 Douglas, B. E., 95(67), 183 Dow, J., 387(37), 408 Downes, H. C., 147(183), 186 Downing, G., 405(90), 410 Drago,R. S., 138, 140(162), 141(159,162, 164), 185, 186, 348(93), 349(93,94,96), 350(93,94), 378 Drenth, W., 152(196), 186, 207,208(5-7,9, 12,13), 208(12,13), 224(5,7,9,13),318 Dressler, K. P., 335(50), 377 Dronov, V. N., 423(184), 481 Dubois, J. E., 108, 109(87,91), 126, 184, 2 12(24), 31 9 Duddey, J. E., 215-217(38), 225-226(38), 31 9 Dueber, T. E., 274(167), 282(177), 288 (177), 289,290(187), 292-293(193), 305 (177), 307(186,193), 310(205), 312(205), 323, 324 Duennebier, F. C., 168(237), 187 Duggleby, P. McC., 426(192,193), 481 Duke, R. B., 240(97), 321 Dulova, V. I., 147(177,178,180-182), I86 Duncan, A. B. F., 334(37), 377 Diirbeck, H. W., 466(223), 482 Dyakonov. I. A.. 4741239). 482 Dimek, C:, 419(137); 428(137), 453(137), 462( 137), 480 Eaborn, C., 17, 31, 33,48(26), 55(31), 58 (31). 79, 80, 152(198), 154(198), 186, 210(17), 214(36), 224(17),319, 464 (2 19), 482 Eanes, R. D., 8,9(13b), 61(2) Eaton, D. A., 39 Eberson, L., 417(62), 421(62), 428(202), 453(62), 456(62), 478, 481 Ebert, M., 333(22), 376 Eckell, A., 1 1 1(149), 185 Eckstein, F., 389, 390,409 Egli, H. A., 17 Eglinton, G., 152(199), 186 Eguchi, S., 218-2 19(50), 227(50), 31 1(50), 320 Ehrenson, S., 2(21,p,3,7), 3(2p), 5(21), 12 (7b), 17,20(7b), 24,26(2p), 29(2P), 33, 44(2), 46(2p), 50(2), 59(2p), 78, 79, 82 (11). 112(11), 138(11),182 Ehrhardt, H., 229-231(79), 320 Eigen, M., 384,408 Eilbracht, P., 329(5), 376 Ekstrom, A., 368(163), 379 Eley, D. D., 418(101), 479 Elliott, J . H., 8 , 9 , 61(2-5)

AUTHOR INDEX Ellison, F. O., 336(57),377 El-Tahiawi, G. M., 314, 315-316(216), 325 Emelyanov, I. S., 423(185), 481 English, P. J. Q., 85(24), 182 Epand, R. M., 385(26), 408 Erlanger, B. F., 400, 401,409 B i n , 0. A., 418(97), 423(97), 479 Evans, A. G., 330(8), 376 Evans, D., 334(48), 355(48), 377 Evans, E., 83, 182 Evans. J . C.. 330(8). 376 Evans; M. G'., 4i+.ii8(20), 418(84), 461 (20), 466,477, 4 7 8 Evans, M. W., 418(88), 378 Evans, W. L., 33 Exner, 0..2(20), 6(2e,6b,c,d,e), 29(4), 44 (2), 47,50(2), 59, 86, 78, 79, 183, 190, 419(147,149,162-164,170), 423(149), 42 4( 188), 42 5( 16 3,164), 42 8( 147,149), 429(149), 431(149), 439(149,163,188), 440( 162,163), 44 1 ( 163). 442 ( 16 3), 445 (163), 448( 164), 449( 163,164), 450(164), 452( 164), 45 3( 149). 456( 149,163,188), 457(149,163,164), 458(149,163), 459 (149), 460(149,188,163), 471(236), 472 (2 36), 480-482 Eyring, H., 417-418(37), 458(37), 461(37), 477 Fahey, R. C., 213, 216(31,42,43), 225(30), 31 9 , 3 2 4 Fainberg, A. H., 261(133), 270(135,155), 417(44), 426(44), 322,323, 4 7 7 Fairclough, R. A., 417,419(31), 428(31), 461(31), 4 7 7 Fajer, J., 359-360(136), 3 7 9 Farrar, J. M., 466(224), 4 8 2 Fassel, V. A., 8 6 , 1 8 3 Fassett, D. W., 168(237), 187 Fawcett, F. S., 6, 14(9), 29(7), 79 Federlin, P., 185 Federova. A. V., 220(56), 221(64,66,67), 222(66), 228(67), 320 Fee, 3. A., 406(103),410 Felton, R. H., 359-360(136),379 Fenton, D. M., 308,324 Fenton, H. J. H., 315, 316,325 Fernandez, L. P., 453(210), 481 Fetzer, U., 313(214), 325 Fiarman, I. D., 469(229), 482 Fichter, F., 100(74), 184 Fickling, M. M., 16, 17,29 Fierens, P. J. C., 426(199), 481 Fieser, L. F., 168(226,227), 169(242), 187 Fieser, M., 169(242), 187 Fife,T. H.,421(173), 456(173),480 Fife, W., 34 Filler, R., 9, 61(8), 78 Fink, W. H., 335(49),377 Finnegan, W. G., 9 Fischer, A., 6, 16, 1 7 , 2 3 , 2 9 , 61(6), 426 (195), 463(195), 481 Fischer, E., 418(98), 479 Fischer, H., 220(54), 274(166b), 320, 323,

481

344,377 Fiske,T. R., 110(134), 185 Fliszer, S., 120(106), 136(155), 185 Flood, M., 419(137), 428(137), 453(137), 462(137), 480 Foglesong, W. D., 264(148), 322 Fojtik, A., 343(76). 377 Foldvary, E.,421-422(176), 425(176), 426 (176,196), 464(176,197), 480, 481 Folkers, K., 405(90), 4 1 0 Forbes, W. F., 379 Forman, E. J., 417(59), 453(59), 464(59), 478 Fort, Jr., R. C., 240(98), 321 Foster, R., 109(84), 184 F O X , I. R., 14(10), 38-42(10), 49(10), 55 (10),79 Fraenkel, G., 85(28), 182 Fraga, S., 334(33), 376 Frank, H. S., 418(88), 478 Frankevich, E. L., 418(105), 479 Franklin, J. L., 206(2), 243(2), 247(2a), 318 Franks, F., 426(194), 481 Freedman, L. D., 191 French, D. M., 147(173), 186 Friedel, C., 210(15), 318 Friedman, M., 109(108), 120,184 Fritz, R. M., 240(97), 321 Frydman, N., 2 7 5 , 3 2 3 Fuchs, R., 9, 23 Fuglevick, W. I., 140(161), 185 Fukui, T., 388,409 Fukumoto, T., 263(141), 322 Furberg, S., 387(37), 408 Furukawa, J., 124,185 Fuson, N., 169(245,246), 187 Fuson, R. C., 243(102), 321

Gal, A., 262(134), 287,299(134,136), 316 (1 34), 322 Galieva, D. R., 147(177), 186 Gallais, P., 256(115), 321 Gallup, G. A., 416(18), 418(18), 463(18), 4 77 Gapon, E. N., 417,420(26), 422(26), 425, 456(26), 457(26), 4 7 7 Gardner, C. L., 359(140), 3 7 9 Gardner, P. D., 221(69), 318,320 Garratt, D. G., 325 Garry, R.,241,321 G a s , J . D., 384, 391(14,65), 392(65),408, 409 Gassman, A. B., 9 Gassman, P. G., 160, 161(216), 187 Gerard, C., 34 Gero, A., 212(24), 319 Gettler, J. D.. 469(229), 482 Geyer, E., 167, 169(238), 1 8 7 Ghenciulescu, A., 310(211), 312(111),325 Gidaspov, B. V., 475(243), 482 Gilbert. R. P.. 309-310(204). 31212041.324 GilkeGn, W.-R., 416(1'8), 418(18), 463 (18), 4 7 7

488

AUTHOR INDEX

Gimarc, B. M., 346(86), 378 Gindl, H., 390(63), 409 Ginzburg, 0. F., 419(159), 423-424(186, 187), 457(187), 480,481

Glass, D. B., 168(237), 187 Gleiter, R., 328(2), 331(2), 333(2), 346 (84), 376, 378

Glew, D. N., 418-419(89), 461(89), 471, 478,482

Glick, R. E., 2(76), 20(76), 79 Gnuchev, N. V., 405(94,96), 410 Goering, H. L., 34 Goetz, E., 184 Gold, V., 260(130), 264(147), 322 Goldstein, J . H., 91(55,57), 95(55), l O l ( 5 5 , 57), 107(80), 183, 184

Gotton, W. C., 157(212), 159,187 Good, V.,418(114),479 Good, W., 426,481 Goodhue, L. D., 147(176), 186 Goodman, J . F., 33 Gorbunov, L. V., 418(99), 479 Gordon, L. B., 91(51), 183 Gordy, W., 141(165,166), 186 Gosavi, R . K., 138,185 Gothardt, H., 152(205), 187 Gottschalk, E. M., 389(54), 409 Gould, E. D., 9 Graham, W. H., 419(143), 428(143), 433 (143), 438(143), 480 Gramstad, T., 140(161,163), 141(163), 185, 186

Granger, M., 120(106), 186 Grashey, D., 111(149), 185 Grashey, R. R., 111(146), 185 Gravestock, M . B., 235(84), 236(85), 248 (84), 249(85), 318(85), 320,321

Graybill, B. M., 417(50), 4 7 7 Greenleaf, A. L., 383(2), 393(2), 396(2), 407

Gregory, L. M., 169(246), 187 Greig, C. C., 138, 185 Greizentein, W., 2 3 Griesbaum, K., 217(48), 218(49), 220(48, 57), 226(48,49), 227(48,57), 320 Grimm, H. G., 4 1 7 , 4 7 7 Grob,C. A.,95(68), 183, 257,259-261, 266,267-269(151), 269(151,153), 297 (121), 301(151), 318,322, 323 Grundemann, C., 256(17), 321 Grunwald, E., 49(27), 80, 82(5), 112-116 (S), 136(5), 262,270(135), 182, 413-414 (2), 418,419(2), 428(2), 433-434(2), 436 (2), 456(2), 460,463(2), 476 Gukrillot, C. R., 463(115,116), 481 Guettk, J.-P., 145(169), 186 Guggenheim, E. A., 147(185), 186 Guilleme, J., 152(204), 187 Guillemonat, A., 22 1(68), 228(68), 320 Gulyaev, N. N., 405(94,96,97), 4 1 0 Gustavson, G., 220(55), 320 Gutbezahl, B., 49(27), 80 Gwyn, D., 34

Haeschemeyer, A. E. V., 386(33), 387(33, 3a,39),408,409

Haffner, J., 229(75), 231(75), 237,245(75), 25 1(87), 264(87), 320, 321

Hafner, K., 329(5), 359-360(1 l), 376 Hald, A.. 431(204), 432(204), 481 Halevi, E. H., 291(191), 324 Hall, F. M.,417(67-71,73),419(71,73), 421 (69,71), 433(69), 462(71,73), 478

Halleux, A., 431(206), 481 Halonen, E. A., 95(70), 283 Halpern, J., 109(99), 184 Hambly, A. N., 414(7), 417(7), 476 Hamill, W. H., 333(24), 359,376 Hamilton, C. L., 385(30), 408 Hammes, G. G., 384,408 Hammett, L. P., 2(2a,2r,7), 4(2a), 44(2), 5 0 (2), 58(2a), 78, 82(1), 182, 212(23), 319, 415.458(16), 463,466,477, 482 Harnmick, D. L., 109(85), 187 Hammond, G. S.. 191 Hammond, P. R., 108-109(83), 184 Hampton, A., 388(45,46), 407,409 Hanack, M., 229(75-79), 230(79), 231,236, 237,243(101), 245(75,77,78), 247(78), 251(86,87), 258(124), 264,274(166b, 167), 275-276(170), 281(176), 282, 283284(170), 288,299(145), 303(170), 305 (176,177), 310, 312(210.21 l ) , 318,320323, 325 Hanazaki, I., 359(134), 379 Hancock, C. K., 421-422(176), 425-426 (176), 464(176), 480 Hannaert, H., 426(199), 481 Hansen, L. D., 417(74,76), 421(74,76), 453 (74,76), 456(74,76), 478 Hansen, R . L., 270(157a), 323 Hanson, J . E., 207(3), 318 Harada, Y., 359(144), 379 Harding, C. E., 274(167), 275-276(170), 283-284(170), 303(170), 321, 323 Hardy, J., 59(36), 80 Hargrove, R. J., 292-293(193), 294, 307 (193), 310(205), 312(205), 324 Harman, R. A., 417(39), 477 Harned, H. S., 414(8), 476 Hamed, R. L., 405(91), 4 1 0 Harnsberger, H. F., 8 3 , 1 8 2 Harper, J . J., 240(98), 321 Harper, P. J., 388(45), 409 Harrison, A. G., 33,90(43,44), 183, 356 (115), 378 Harter, D. R., 263(138), 322 Hartley, B. S., 398,409 Hartman, R. J., 9 Hartzler, H. D., 310(207), 324 Harvey, R. G., 55(30), 80 Haselbach, E., 345(83), 378 Hashmall, J . A., 334(34), 336(34), 338(34), 344(34), 356(34), 376 Hata, Y., 23, 26(13), 79 Hatch, L. F., 2 3 Hatch, L. F., 91(51), 183 Hauser, C. R., 9,437(208), 438(208), 446

AUTHOR INDEX (208),481 Hausser, K. H., 369(167),379 Hayaski, Y.,398(79), 402(79), 409 Heck, R., 33,270(155), 323 Heffley, P., 9 Hegeman, G.D.,405(101). 406(102,103), 410 Hehre, W. J., 274(166a), 323 Heilbronner, E.,6(6a), 29(4), 95(61), 147 (61), 161(61), 328(3), 183,376 Heimo, S., 417(42), 426(42), 477 Hein, G. E.,385,396-398,400(75), 408, 409 Hekkert, G. L.,208-209(12,13),224(13), 318 Hellerman, L., 256(115), 321 Helmreich,W., 110(138), 185 Helper, L. G., 419(134-136), 428(134-136), 453(134,210,21 l), 457(135), 461,462, 463(136), 479,481 Henderson, I. H. S., 356(114), 378 Henderson, R., 384(20,22), 385, 396(20),

408 Hendlin, D., 405(99), 410 Hendemann, G.,292(195), 324 Henglein, A., 333(33), 376 Hennion, G.F., 221(62), 295(199), 310 (206),320, 324,325 Henrick, C., 16,29(7), 86 Henry, R. A., 9 Heppolette, R. L.,418-419(90),461(90), 478 Hercules, D. M., 373(177,180), 380 Herk, L., 110(111), 121,124(111), 184 Herterich, I., 229(75-77),231(75-77),245 (75,77),320 Herzberg, G., 348(91), 351(91), 355(91), 358(91), 364(91), 378 Het2er.A. B., 6(7), 29(10), 61(1), 86 Heumann, A., 236,251(86), 321 Hidy, P. H.,405(91), 410 Higasi, K.,90(42), 183 Hillier, I. H., 334(44), 377 Hinchliffe, A., 349(98), 359(130,151), 378, 379 Hine, J., 83,94,95(16), 182 Hinshehvood, C. N.,417,418(115,116), 419(31,115,116), 422(34,35,38), 428(31, 1 15,116),433( 1 15,116), 436( 1 15,116), 448(34), 456(115,116), 458,461(31, 116), 477,479 Hirota, K., 330(9), 376 Hirshberg, Y.,418(98), 479 Hirst, D. M.,359(122), 378 Hixon, R. M., 147(176), 186 Hixon, S. C.,308(203), 310(203), 312 (203). 324 Hobza, P., 333(17), 359(11,17), 360(11), 376 Hochmann, P., 328(4), 376 Hodge, E. B., 405(91), 410 Hoen, R. E.,256( 115), 321 Hoffmann, R., 272,279(175a), 291(188), 323,324,328(1,2), 331(1,2), 343,346

4 89

(84),376-378 Hogeveen,H.,91(50),94,95(50,58), 99, 100(50,58), 183, 207(8), 224(9), 318 Hohlneicher, G.,359(135), 379 Hoijtink, G.J., 330(6,7), 331(13), 333, 359 (148-150),360(6,7,13,146,148,154,155), 376, 379 Holland, R. J., 107(79), 184 Holles, D. P., 387(40), 409 Holston, J. H., 214(34), 319 Holtz, D.,53(29), 80 Hopkinson, A. C., 272-273(164),323 Horeux, C., 17 HBrig,C., 256(117),321 Hqrner, L., 167, 169(238), I87 Hornfeld, H. L., 55(31), 58(31), 80 Howe, E., 405(90), 410 Hoyland, J. R., 342(70), 377 Hoytink, G. J., 357(117), 378 Hsu, Y. F. L., 1 1 1(144), 185 Hu, T.,453(21 l), 481 Huang, S.J., 263,322 Hudson, R. F., 136(155), 185 Hughes, E. D., 243(103), 261(133), 321, 322 Hugill, J. A. C., 243(106), 321 Hulett, J. R.,470-471(230),482 Hiimbelin, R., 467(227), 482 Hume, D. N.,417(59), 453(59), 464(59), 478 Humffray, A. A., 423(180), 481,482 Huml, K., 347(88-90). 378 Hummel, K., 229(78), 231(78), 245(78), 247(78), 274(166b9167), 275-276(170), 283-284(170),303(170), 320, 323 Humphrey, J . S.,292(195), 310(208), 324, 325 Hiinig, S., 168(236), 187, 359(142,143), 360(143), 372(175),379, 380 Hunnewell, B. D.,405(90), 410 Hunter, D. H., 277(171), 323 Hunziker, H., 217(47), 319 Hush, N. S., 352(106), 354(106), 356(106), 378, 380 Husigen, R., 33, 111(146,147,149-lS1),152 (205), 185, 187 Huyberechts, S.,431(206), 481 Huzinaga, S., 334(31,32), 376 Ibaria, P. A., 223(74), 228(74), 320 Ibata, T., 33 I’Haya, Y. J.. 359(138,139), 379 Ikegami, S.,23,26(13), 79 Ikehara, M.,388,409 Illuminati, G., 24, 33 Imamura, A., 291(188), 324 Imhoff, M. A.,274(167), 282(177), 288 (177),323 Indelicato, J. M.,269,271,301(158), 316 (154),323 Inglis, H. S.,417(49), 477 Ingold, C. K.,261(133), 365(114), 417(22), 466,322,378, 477 Inukai, T., 1 1 1(143), 126,185

490

AUTHOR INDEX

Ishitani, A., 330(10), 338(10), 341(10), 359 (10,141), 376, 379 Ishitobi, H., 23,26(13), 33, 79 Istomin. B. I., 419(171), 480 Itoh, M., 369(170), 380 Ivanoff, N., 415(15), 458(15), 477 Ivanov, P. A., 475(243), 482 Ives,D. J. G., 418(79,80,81), 419(79), 426 (194), 462(79), 478, 481 Iwatani, K., 332(16), 376 Izaki, K., 403(85), 405(85), 410 Izatt, R . M., 417(74-77), 421(74-77), 453 (74-77), 454(75), 456(74-77), 478

Jackson, R. A., 425(191), 481 Jacobs, T. L., 207,208(4), 217(47), 221, 222(65), 228(65), 238,239,241,242, 253(91), 264(91), 308,318-321, 324 Jacobsen, R . R., 34 Jaffe,H. H., 2(2b,2h,5), 6(8a), 9 , 2 3 , 29 ( l l ) , 40(2b), 44(2), 50(2), 78, 82(2,12), 83,182, 191,354, 355, 357, 358,378, 416(17), 426(17), 464(17), 477

Jagow, R. H., 324 Jagur-Grodzinski, J., 367(160), 3 7 9 James,D. G. L., 110(125,126), 124(125), 125,185

James, E.. 393(68) James, H . L., 82(12), I 8 2 Jam=, T. C., 95(66), 168(237), 183 James, T. J., 187 Janssen, M. J., 136(154), 185 Janssens, W., 419(157), 423(157,182), 428 (157). 458(157),480,481

Jardetzky, R. M., 385,408 Jencks, W. P., 404(89), 410 Jenkins, A. D., 125(127-129), 185 Jenkins, D. I., 17 Jensen, A. L., 168(234), 187 Jensen, J. L., 260(127), 322 Jensen, L. H., 387(35,37), 408 Jensen, M. B., 147(186), 186 Jewett, J. G., 292(195), 324 Jindal, S. P., 240(98) Jira, W., 33 Joern, W. A., 152(207), 187 Joesten, M. D., 140-141(162), 186 Johnson,C.D., 138,185, 417(72), 474 (238), 478, 482 Johnson, L. N., 384(21), 408 Johnson, R., 125(127), 185 Johnson, R. N., 217(47), 221-222(65), 228 (65), 249(85), 3 1 9 , 3 2 0

Johnson, W. S., 235,236(85), 249(84), 318, 320,321

Jolly, W. L., 17 Jonas, J., 6(6b), 29(4), 47, 79, 190 Jones, B., 34 Jones, D. A. K., 9 . 2 3 Jones, H. W., 270(135), 322 Jones, M. M., 416(18), 418(18), 463(18), 477

Jones, W. M., 256,263,270,293,294,297 (114), 299(140), 316(140), 3 2 1 , 3 2 2

Josien, M. L., 169(245,246), 187 Jouve, P., 152(203), 186 Jula, T. F., 321 Julian, D. B., 168(237), 187 Kahan, F., 405(100), 407,410 Kahan, J., 405(100), 410 Kaiser, E. T., 4 0 2 , 4 1 0 Kamat, R . J., 232,234(82), 247(82),249 (82), 320 Kampmeier, J. A.,255-256(113), 297(113), 321

Kanamaru, N., 359(137), 379 Kaphn, C. A., 2 3 Kapuler, A. M., 388(44,52), 389, 409 Kapustin, Yu. M., 419(140), 462(140), 480 Karplus, M., 48(24), 79 Kasai, P. H., 399(97). 378 Kasiwagi, H., 107(77,78), 184 Kaspi, J., 263,322 Kato, H., 256(116), 272(162), 350(99), 321,323,378

Katritzky,A. R., 21(11), 2 4 , 2 6 , 28,40-41 (14), 79, 85(24), 182, 417(72), 474(238), 478,482 Kaufman, D. A., 261(131), 262.297(131), 313, 316(131),322. 325 Kawabata, N., 124.185 Kawamura, T., 350(99), 378 Kearns, G. L., 90(40), 183 Kebarle, P.. 33,90(43), 183 Keblys, K. A., 109(100), 184 Keefer, R. M., 108(82), 184 Keeffe, J. R., 260(127),322 Keene, J. P., 333(22), 376 Kell, D. R., 219(53),320 Kelly, J. F., 320 Kelsey, D. R., 258(122), 274(122), 278, 279(122,174,175b), 280(175b), 305 (175b), 3 1 1 , 3 2 2 , 3 2 3 Kemeny, G., 418(102), 420(102), 457(102), 463(102), 479 Kenyon, C . L., 383(2). 392(2), 393(2,71, 72), 394(71), 396(2,71), 405(101), 406 (102,103),409, 410 Kernagham, G. F. P., 279(175a), 323 Kerr, J.A., 110(135,136), I 8 5 Kessick, M. A., 260(130), 322 Khait, Yu. L., 418(127), 428(127), 461 (127),479 Khami, K. S., 24 Kharsch, M. S., 217(47).319 Khomutov. R . M., 405(94-96.98). 41 0 Kieffer, F., 16, 29 Kiehlmann, E., 270(156), 322 Kienle, R. H., 33 Kiesslich, G., 359(142), 379 Kikuchi, O., 341(67), 357(67), 377 Kilpatrick, M., 8 , 9 , 17, 61(2-5), 8 7 Kim,C. J., 291(189),324 Kim, I. N., 147(178), 186 Kim, J. P., 85(28), 182 Kimura, K., 359(145), 379 Kindler, K., 9 , 2 3

AUTHOR INDEX King, G. W., 334(45), 357(45), 3 7 7 King, P. A., 213(26), 319 Kirby, F. B., 213(26),319 Kiritani, R., 263(141), 322 Kirova, A. V., 419(140), 462(140), 480 Kirrman, A. P., 185 Kirkwood, J. G., 59(33), 80 Kleinschuster, J. J., 406(104,105), 407 (105),410 Klopman, G., 342(71), 344(71), 3 7 7 Kloster-Jensen, E., 152(194,195), 186 Knuteson, G., 33 KO, H. C., 453(21 l ) , 481 Koch, H. F., 17, 39(20), 40(20), 50(28), 79 Kochi, J. K., 190 Kohnstam, G., 419(168,169), 480 Koivisto, A., 417(42), 426(42), 477 Kojima, T., 1 1 1(143), 126, I85 Kolfus, K., 6(6d), 29(4), 8 7 Kollmar, H., 342(49), 344,345(69), 377 Kolsaker, P., 120(101,102), 184 Kommandeur, J., 336(56), 359(56), 377 Koock, S. U., 239(93-95), 240(94), 241, 251(94,95), 253(93), 321 Korpiun, O., 423(181), 481 Korte, F., 161(217), 163, 187 Kortum, G., 61,95(64), 136(64), 147(64), 183 Kortzehorn, R. N., 334(43), 377 Kosower, E. M., 369(169), 380 Kostikov, R . R., 474(239), 482 Kouteckq, 331(14), 376 Kovaleva, G. K., 405(94-96), 4 1 0 Kbvendi, A., 482 Kozlova, M. F., 417(58), 423(58), 478 Kraihanzel. C. S.. 153(200), 186 Kraut, J., 387(35), 408 Kreevoy, M. M., 154(206), 187 Kresze, G., 423(181), 481 Krishnaswamy, P., 392(67), 409 Kross, R. D., 8 6 , 1 8 3 Kruglyak, Yu. A., 359(132,133), 379 Kruys, P., 431(206), 481 Krylov, V. K., 417(57,58), 423(57,58), 426 (57), 443(57), 445-446(57), 478 Krysick, H. R., 16,29 Kubota, T., 332(16), 376 Kucherov, V. F., 169(247), 174,220(56), 187,320 Kudrynski, J., 417(70), 478 Kuehl, F. A., 405(90), 410 Kuhn, A. T., 147(174), 186 Kuhn, R., 16,29 Kuivila, H. G., 277(172), 323 Kulich, E., 425(189), 457(189),481 Kume, S., 367(160), 379 Kuntz, I., 417(55), 478 Kuprievich, V. A., 359(133), 379 Kurland, R . J., 24, 33, 34 Kurz, J. L., 466(224), 482 Kushner, A. S., 295(201),324 Kustin, K., 384,408 Kutner, A., 254(107), 321 Kuwata, K., 330(9), 376

491

Kvalnes, D. E., 168(231-233), 169(239), 187

KvasniEka, V., 328(4), 376 Kvyat, E. I., 419(159), 480 Kwart, H., 147(187,188), 186 Kwok, W. K., 176(256), 188 Lagowski, I. J., 333(20), 376 Laidler, K. J., 415(13), 417(35,37,63-66), 418(13,37), 422(35), 453(63-65), 456(6366), 458(13,35,37), 461(13,37). 466,477, 478, 482 Lakomy, J., 6(2e,6e), 29(4), 87, 88 Lakshminarayanan, A. V., 387(34), 408 Lamaty, G., 292(194), 295(194), 324 LaMer,V. K., 147(183), 168(225), 186, 187, 417(53), 478 Lamm, B., 260(127), 322 Lancelot, C. J., 291(189), 324 Landgrebe, J . A., 161(219), 1 8 7 Lane, C. A., 213(26),319 Lannung, A., 418(83), 478 Lansbury, R. C., 373(177), 380 Larrson, E., 185 Larson, J. W., 419(136), 428(136), 463 (136),479 Laszlo, P., 268-269(152), 232 Lathan, W. A., 274(166a), 323 Latta, B. M., 58(32), 8 0 Latzko, W., lOO(74). 184 Lauger, P., 95(63), 183 Laurgeau, C., 152(201), 186 Lawrence, P. J., 403(86), 410 Lawson, W. B., 398, 399,402(79), 409 Leach, S. J., 385(24), 408 Leandri, G., 223(73), 320 Leary, G. J., 17 Lebas, J . M., 169(246), 187 Lebedev, Ya. S., 418(108), 410 Ledaal, T., 120,184 Ledbchowski, A., 475(244), 482 Lee, B., 404(88), 410 Lee, C. V., 310(205), 312(205), 324 Lee,D. J., 213,216(31,42),225(30),319 Lee, I., 419(165-167). 4 6 5 , 4 8 0 Lee, L. H., 109(95), 184 Lefebvre, R.. 334,359(121), 376, 378 Leffler, J. E., 82(5), 112-116(5), 128, 136 ( 5 ) , 4 13-414( 1,2), 416( 1,19), 4 17(2 ,SO), 418,419, 423(152), 426(19), 428(1,2, 143,152,153), 431(153), 433(1,2,143), 434(1,2), 436(1,2), 437(1). 438(1,143, 15 3), 456( 1,2,153), 457(152,153), 460, 463(2,19), 464(2), 465,476(1), 476, 477, 480 LeGall, C. Y., 240(97), 321 LeGras, J., 221(63), 320 Leibler, E., 9 LeNoble, W. J., 95(65), 310(209), 183,325 Leontev, V. B., 147(178), 186 Lessard, M. V., 263,322 Letsinger, R. L., 215(37), 31 9 Leung, C., 5(8), 79 Leung, H. W., 325

492

AUTHOR INDEX

Leveson, L. L., 425(190), 457(190), 481 Levy, D. H., 335( 18), 376 Levy, J., 256(115),321 Levy, J . B., 421(174),480 Lewis, E. S., 33,48(26), 79, 294,324 Lewis, I. C., 2(2f,5,7b), 3(2f), 4(2f), 12(7b). 14(10), 20(7b), 38-42(10), 44(2), 49(10), 50(2), 55(10), 83, 78, 79. 182 Lichtenthaler, F. W., 91(52), 183 Lieber, E., 417(54), 478 Likhtenshtein, G. I., 418(113,122,129,130), 425(130), 428(122,129,130), 457(122, 129,130), 461(122,129,130), 463(113), 4 79 Linder, R. E., 426(196), 464(196), 481 Linetskaya, Z. G., 418(106), 479 Ling, A. C., 426(196), 464(196), 481 Linhart, F., 372(174), 380 Linnett, J . W., 359(122,123), 378 Linnik, Yu. V., 432(207), 439-440(207), 481 Linstead, R. P., 417(51), 478 Liotta, C. L., 29 Lippert, E., 165(224), 187 Lipsett, M. N., 389(55), 409 Liu, L. H., 191 Liu, L. K., 323 d e l l a n o , C., 344(80), 377 Lo, D. H., 344(79), 377 Lo, L. W., 401-402(82), 410 Loewenstein, A., 152(196), 186 Long, F . A . , 147(175), 186, 415(11),477 Longuet-Higgins, H. C., 334-338, 341, 343, 345, 352, 354-358, 359(27), 376, 377, 4 18( 126), 42 8( 126), 45 7 ( 12 6), 461 ( 126), 479 Lorquet, J. C., 334,377 Lossing, F. P., 33, 90(43), 183, 354(108, 109), 356(114-116), 378 . Lowitz, D. A., 340(62), 359(62), 377 Lurnry, R., 475(247), 482 Lupinski, J . H., 360(154), 379 Lupton, Jr., E. C., 2(2q), 12,28, 31,44(2), 50(2), 78, 8 5 , 150,182 LuValle, J. E., 147(172), 186 Lykos, P. G., 377 Lynch, J. L., 405(93), 410 Lyons, J. E., 405(90), 410 Lyssy, G. H., 95(61), 147(61), 161(61), 183 Lyyra, J . P., 417,426(42), 477 McBride, W. R., 431(205), 481 McBryde, W. A. E., 418(112), 457(112), 461-462(112),479 MacCallurn,D., 110(125), 124(125), 185 McCarry, B. E., 236(85), 249(85), 318(85), 321 McClellan, A. F., 147(193), 152(193), 157 (193), 186 McClelland, 8. J . , 343, 368,377 McConnell, H. M., 385(30), 408 McCreary, J . R., 418(93), 419(161), 479, 480

McCullough, J . D., 426(198), 481

McDaniel, D. H., 2(2d), 6(la), 29(1), 44(2), 50(2), 61(6), 78, 8 5 , 1 8 2 McDiarrnid, 334(36), 377 McDonald, C. C., 385(25), 408 McDonald, R., 325 McDougall, A. O., 147(175), 186 McElrath, E. N., 240(97), 321 McGregor, R., 418(91), 423(91), 479 McGriff, R . B., 385, 397(31), 408 Maciel, G. E., 24 McKeever, L. D., 17, 34, 39-40(20), 50(28), 79 Mackor, E. L., 331(13), 333(13), 360(13), 3 76 McLachlan, A. D., 349(95), 360(156), 378, 3 79 McLaughlin, A. C., 393-394(71), 396(71), 409 McNab, J . G., 217(47), 319 McNab, M. C., 217(47),319 Macomber, R. S., 238,239, 241,242, 253 (91,100), 264(91), 295(199), 321, 324 McQuillin, F. J., 219(53), 320 McUllough, J . D., 9 McWeeny, R., 334,376 Magat, J., 415(15), 458(15),477 Maguire, J. A., 159, 187 Mahler, H. R., 383,408 deMaine, M. M., 406(104,105), 407(105), 41 0 Mair, G. A., 384(21), 408 Malawski, M. J., 419-423,425, 428(150, 151),438(151), 456(151),458(150),480 Maloney, D. E., 295(199), 310(206), 324,

325 Malysheva, E. N., 417(82), 478 Mamantov, A., 126, 185 Manecke, G., 168(228), 187 Maness,D. D., 2 6 3 , 2 7 0 , 2 9 3 , 2 9 4 , 2 9 9 (140), 316(140),322 Mann,B. R., 6(lb), 16, 17,23, 29, 61(6), 79 Marchand, A. P., 9 d e la Mare, P. B. D., 108, 109(94), 184 Marerntie, V. M., 419(154,155), 421(154, 155), 423(154,155), 426(154,155), 428 (154,155), 439(155),480 Markgraf, J. H., 419(144), 428(144), 431432(144), 480 Marsden, P. D., 418-419(79), 462(70), 478 Marshall, R . M., 471(234), 482 Martin, J . C., 264(148), 322 Martin, M., 141(167), 186 Martin, R . H., 426(199), 481 Martinez, A. G., 281(176), 282(176,177), 288(177), 305(176,177), 323 Maslentsova, T. A., 147(180,181), 186 Matesich,M. A., 210(19), 212(25), 213(29), 214(25), 224(19,25), 319 Matheu, F. M., 336(57), 377 Matsuhashi, M., 403(85), 405(85), 4 1 0 Matzura, H., 389(54), 409 Maurer, A., 373(178) Mavrov, M. V., 220(56), 320

AUTHOR INDEX Maxfield, M. W.,85(30), 79 Mazur, Y.,323 Meadows, D.H.,385(26,270), 408 Meakins, R. J., 418(100), 479 Meier, J., 91(54), 95(54), 101(54), 183 Meier, W., 16,29(7), 78 van der Meij, P. H., 360(146), 379 Meislich, H.,83,94,169(15), 182 Meister, A., 384, 390, 391, 392(65-67), 408, 409 Melamud, S. G., 418(97), 423(97), 479 Melander, L., 291(191),324 Melloni, G.,284(179,180), 285-296(181), 323 Menzinger, M., 414-415(10),477 Merenheimo, S.,474(240), 482 Merrill, S. H.,9,61(8), 78 Metzler, D.E.,405(98), 410 Metzler, G.,373(178), 380 Meyers, C.Y.,191 Michelson, A. M., 388,409 Middaugh, R. L., 141(164), 186 Milburn, R. M., 418(111), 462(111),479 Mildvan, A. S.,407(106), 410 Mile, B., 336(15),376 Miles, D. H.,235(84), 249(84), 320 Miles, F. B., 263(138), 322 MiliCeviC, B., 418(91), 423(91), 479 Miller, E. B., 48(26), 79 Miller, F. W.,256,297(114),321 Miller, J., 23 Miller, L. L.,261(131), 262,297(131), 313, 316( 131), 322,325 Miller, M. L., 417(53), 478 Miller, S. I., 9,88(39), 176,183, 184,188, 473,482 Millie, P., 334(35), 364(35), 377 Milne, G.W.A., 17 Mindl, J., 475(242), 482 Minkin, V. I., 417(82), 478 Mitra, S. S., 157(21 l), 187 Miyazaki, H.,332(16),376 Mizuno, M., 369( 171), 380 MBbius, L., 1 1 1( 147), 185 Modena, G.,217(45), 258(123), 284,285 (180,181),286(181,182,183), 287(183, 184), 307(182), 318,319,321,322,324 Moffitt, W.,243(105), 321, 359(119), 378 MOhle, ad W.,169(241), 187 M o i t a , H.,9 Molyneux, P.,419(158), 428(158), 480 Monkhorst, H.J., 336(56), 359(56), 377 Monny, C.,388,409 Montiju. P. P., 222(71), 320 Moore, D.R., 110(110), 184 Moore, D.W.,333( 19), 376 Moran, H.W.,308(203), 310(203), 312 (203),324 Mori, Y.,359(127), 379 Moriconi, E. J., 320 Morigagi, K.,330(9), 376 Morihofer, A.,6(6a), 29(4), 95(61), 147 (61), 161(61), 183 Morman, J. F., 152(199), 186

493

Morris, H. F., 310(209), 325 Morrison, J. F.,393(68-70), 409 Moseley, P. G.N., 417(81), 478 Moser, C.,359(121), 378 Moskowitz, J. W.,335(53),377 Moss, R. A., 126,185 Moureu, C.,212(22),319 Mouvier, G.,108(87,89), 109(870, 126,184 Mozdor, E. V., 359(132,133), 359, 379 Mueller, W.H.,217(46),319 Mui, J. Y-P., 321 Mulliken, R. S., 343, 375(182), 377, 380 Murkn, R.,474(240), 482 Murr, B. L.,292(194,195), 295(194), 324 Murrell, J. N., 359(151), 369(167), 379 Muzalewski, F.,422(178), 480 Myers, R. F., 235(84), 249(84), 320 Myers, R. J., 333(18), 376 Myher, J. J., 141(168), 186 Naegele, W.,217(48), 220(48), 226-427 (48),320 Nagakura, S., 330(10), 338(10), 341(10), 359(10,137,141),369(170), 376,379,

380 N a i , P. M., 352, 356(106), 378 Nakatsuji, H.,272(162), 323, 350(99), 378 Nakayama, M., 359(138,139),379 Naso, F.,284(179,180),324 Natherstad, J. J., 24 Nazaruv, I. N., 217(44),319 Nazy, J . R., 215(37),319 Nelson, J. H.,55(30), 80 Nenitzescu, C.N., 206(1), 318 Nesbet, R. K.,334(25), 337(25), 376 Neuhaus, F. C.,405(93), 410 Neumann, D.,334(48), 355(48), 377 Neurath, H., 398,409 Newitt, D.M., 417(51,52), 478 Newman, B., 6(8b), 9,29(1 l), 78 Newman, M. S., 9,61(8), 254(108,109), 255(108,112),321 Newson, H.C., 418(118), 420(118),479 Newstead, E.,405(90), 410 Nicholas, J. F., 418(121), 428(121), 461 (121), 479 Nicholas, R. D., 240(98), 321 Nieboer, E., 418(112), 457(112), 461-462 ( 1 12), 479 Niedzielski, R. J., 141(164), 186 Niemann, C., 385, 396-398,400(75),408, 409 Nishikida, K., 332(16), 376 Nishimura, A., 256(116), 321 Niwa, J., 91(56), 101(56), 107(77,78), 183, 184

Nixon, A. C., 33 Noble, P.N., 334(43), 377 Nordlander. J. E.,240(98), 321 Norman, R. 0.C., 23 North, A.C. T., 384(21), 408 Noyce, D. S.,210,211,212(25),213(26, 28), 214(20,25,28), 224(19,20,25,28), 260(130), 263(138), 292,319,322

494

AUTHOR INDEX

NUrnberg, H. W., 466(223), 482 Nurro, A., 474(240), 482 Oae, S., 263(141).322 Oakenfull, D. G., 389,409 O’Brien, D. H., 137, 285 Ozendxkovd, D., 347(87,88), 378 O’Connor, R., 255-256(113), 297(113),322 Odell, B. G., 346(84), 378 O’Driscoll, K. F., 318(219), 325 O’Ferrall, R. A. M., 176(253,255,256), 188 Oftedahl, E. N., 215(37),319 Ogilvie, K. K., 388,409 O’Hara, W. F., 419(134,137), 428(134,137), 453(134,137,21 l ) , 462,479-481 Ohta,M., 256(116),321 Oishi, Y., 332(16), 376 Ojelund, G., 419(141), 462(141),480 Okamoto, Y.,2(2c,7), 31, 33,44(2), 5 0 ( 2 ) , 78, 79, 259(125),322 Okorie, D. A., 235(84), 249(84), 320 Okorodudu, A. 0. M., 254(109),321 Okuzumi,Y., 152(197), 154(197), 155,286 Olah, G. A., 137,185, 294(201), 324 Oldfield, L. F., 169(244), 187 O’Leary, B., 342(71), 344(71), 3 7 7 Oloffson, G., 138, 141(170), 185 Omura, I., 90(42), 183 Oosterhoff, L. J., 360(154), 379 Orda, V. V., 4(8), 79 Orloff, D., 375(182), 380 Orloff, H., 375(182), 380 Ormond, R., 405(90), 410 Oth, J . F. M., 333(21), 376 Oto, E., 405(92), 420 Orville-Th0mas.W. J.. 157.187 Oscarson, J. L.,’417(75), 421(75), 453-454 (75), 456(75), 478 Oue, S., 85(27), 182 Owen, B. B., 414(8), 476 Owen, E. D., 330(8), 376 Packer, J., 16, 17, 29 Page, J . E., 9 , 61(7), 79 Palm, V. A.,2(2j), 44(2), 78, 82(6), 112116(6), 282, 413-414(3), 418(120), 219(3, 154,155,171), 42 1(3,154,155), 423(154, 155,179), 426(3,155), 428(3,154,155), 433-434(3), 436( 3), 438( 3), 4 39( 1 5 5) , 456(3), 457(120), 460,464(2,217), 476, 479-481 Pamiljans, V., 392(67), 409 Paoletti, PI, 417(60), 478 Papee, H. M., 417(63-65). 453(63-65), 456 (63-65), 478 Parini, V. P., 418(105), 479 Paris, M. T., 95(62), 183 Parish, R. C., 5(8), 79 Park, Y. J., 419(166), 480 Parker, S. H., 17 Parkin, D. C., 59(36), 80 Panoch, H. J., 168(228), 287 Parr, R . G., 272(160), 323 Parry, R. J., 235(84), 249(84), 320

Pascual, C., 91(54), 95(54), 101(54), 107 (54), 283 Patai, S., 110(109), 120, 184 Patterson, A., 147(173), 286 Paule, R. C., 419(160), 425(160),480 Pauling, L., 243(106), 321 Paulson, D. R., 223(73), 320 Pearson, J. M., 110(130), 185 Peck, R. L., 405(90), 420 Pedersen, L., 350,378 Pederson, K. O., 168(234), 187 Peer,H. G., 221(58),320 P’eng, S. L., 417(51), 478 Peover, M. E., 168(230), I 8 7 Petrov, A. A., 220(56), 221(64,66), 222 (66), 320 Perrault, G., 423(183), 481 Person,W. B., 157(212), 159,287 Petersen, H., Jr., 348(93), 349-350(93,94), 3 78 Peterson, H. J., 33 Petersson, G. A., 349(95), 378 Peterson, P. E., 109(98), 184. 210(19). 212 (25), 214(25), 215, 216(38,40,41), 217, 224( 19,25), 225-226(38), 2 32,234( 82), 247(82), 249(82), 269,271, 301(158), 316(154), 318,329, 3 2 0 , 3 2 3 Peterson, R.C., 419,425,428(144,148), 431-432(144), 4 5 6 , 4 8 0 Pews, R. G., 9 , 2 3 , 34,44(23), 79 Peyerimhoff, S. D., 334,377 Pfaendler,H. R.,260(129), 269(153),322, 323 Pfeifer, W. D., 274(167), 275(170), 276 (170), 283-284(170), 303(170), 323 Philips, D. H., 359(131), 379 Philips, J. C., 295(201), 324 Philips, W. D., 369(168), 380 Phillips, D. C., 384(21), 408 Phillips, W. D., 385,408 Phillips, W. F., 405(91), 410 Pihl,A., 419(156),421(156), 424(156), 426(156), 428(156), 451-452(156), 480 Pihl, V., 419(156), 421(156), 424(156), 426(156), 428(156), 45 1-452(156),480 Pincock, J . A., 214(35), 217(32,33), 225 (33), 329 Pinzelli, R. F., 24,26(14), 40-41(14), 79 Piscitelli, M., 284(179), 324 Pittman, C. U., 221-222(70), 294(201),320, 324 Pivonka, P., 475(242), 482 Placito, P. J., 109(85), 184 Plante, E. R., 419(160), 425(160), 480 Plowman, K. M., 383,408 Podosenova, N. G., 418(104), 479 van de Pod, W., 417(78), 419(78), 453(78), 462(78), 478 Pohland, A., 405(91), 420 Polanyi, M., 417-418(20), 461(20), 466, 477 Pollack, R. M., 260( 130), 322 Pop, M., 456(212), 481 Pople, J . A., 48(24), 79, 274(166a), 323,

AUTHOR INDEX 334-338,341,345, 346(66,85), 347(85), 350(85), 352,354-358,359(27),376-378 Popov,A. I., 157(212), 159,187 Popova, I. A., 147(182), 186 Popovici, S.,456(202), 481 Porai-Koshits, B. A., 475(246), 482,482 Porto, A. M.,17 Pottie, R. F., 356(116), 378 Potts, A.W.,334(48), 355(48), 377 Poutoma, M. L., 221(59), 223(74), 228(74), 320 Povarov, Yu.A., 475(243), 482 Prasad, D.,417(80), 478 Pratt, R. E., 107(79), 184 Pregosin, P. S., 17 Prelog, V.,384,408 Pressman, D.,9 Preston, J., 213(27), 319 Price,C. C., 85(27), 121, 122, 124,182, 184,185 Price, E., 14(10), 38-42(10),49(10), 55(10), 79 Price, M. B., 147(187), 186 Price, M. J., 156,187 Price, W.C., 334(48), 355(48), 377 Prigge, H.,165(224), 187 Pring, M., 109(96), 184 Pryor, W.A., 110(134), 185 Purlee, E. L.,419(142), 428(142), 431-432 (142),480 Purnell, J. H.,471(234), 482 Putter, I., 405(90), 410 Pyron, R. S.,130, 131,185 Queen, A., 419(169), 480 Quinn, R. K., 333(20), 376 Quiocho, F. A., 384(18). 408 Ragsdale, R. D., 55(30), 80 Raistrick, B., 417(52), 478 Rajender, S., 475(247), 482 Rakshys, Jr., J. W., 2(6), 79 Ramachandran, G. N., 387(34), 408 Ramsey, N. F.,48(24), 79 Rao,C. N. R., 86, 138,183,185,417(54), 478 Rappoport, Z., 110(109), 120,184,258 (123,124),262,263,277-278(173),287, 288(173,185), 299(134,136), 305(173), 316( 1 34), 322-324 Rasschaert, A., 419( 157), 423( 157,l82), 428(157), 458(157), 480, 481 Ray, G. J., 24, 34 Ray, N. H.,5(8), 79 Rdboul, E.,217(47), 319 Reddy, G.S.,91(59), 101(57), 183 Ree, B. R., 264(148), 322 Reece, I. H.,417(67,68), 478 Reed, R. I., 355(112), 378 Reed. W. L.. 213f26). 319 Reguiski, T.'W., 325" Rehman, Z.,2 18(49), 226(40), 320 Rehner, J.. 418(109), 463(109), 479 Reich, E.,389,409

495

Rejholec, V.,359-360(11),376 Rennick, L. E.,295(201), 324 Resnik, R. K.,95(67), 183 Rettschnick, R. P. H.,357(117), 378 Reuben, J., 385(29), 408 Rheault, P., 388,409 Rice, 0. K., 418(87), 461(87), 478 Rich, A., 386-387(33),408 Richards, F. M., 384(17,18), 408 Richards, W.G.,353,378 Richardson, Jr., D.I., 389(58), 390,409 Richey, Jr., H.G., 206(2), 243(2), 295 (201), 318, 324 Richter, P., 168(236), 187 Rickey, J. M.,206(2), 243(2), 318 Rieke, C. A.,375(182), 380 Ring, R. N., 110(110), 184 Ritchie, C. D.,2(2m), 5(2m), 14,44(2), 50 (2). 64(2m), 78, 82(8), 112-115(8), 121, 182, 418,421(124), 428(124), 457(124), 461(124), 464,479 Ritter, J. D. S., 9 Rittie, J. D. S.. 176(254), I87 Rixon, F.W.,17 Roberts, B. G.,373(178), 380 Roberts, G.,359(147), 379 Roberts, G. C. K., 385(27), 408 Roberts, J. D.,6,9,243(104), 321 Roberts, J. L., 2(2h,5), 44(2), 50(2), 78 Roberts, R. D.,240(96), 321 Robertson, R. E.,417(41), 418-419(89,90), 426(41), 461(89,90), 471(231), 477,478. 482 Robins, R. K., 388, 389(50), 409 Robinson, G.C.,261(133), 270(155), 322,

323 Robinson, R. A., 16,29 Robinson, R. E., 191 Robson, P., 33 Roe, D. K., 373(177,180), 380 Roginskii, S. Z.,418(127), 428(127), 461 (127),479 Roginsky, S., 417,461(29), 477 Roman. S. A.,234(83), 249(83), . . 320 Roosen, R., 464(21'8); 482 Roothaan, C. C. J., 334, 335, 336(29), 337, 340, 341, 352,376 Rose, I. A., 407(106), 410 Rosenberg, B., 418(102), 420(102). 457 (102), 463(102), 479 Rosenberg, E.Y.,405(101), 410 Rosenkewitsch, L., 417,461(20), 477 Ross, S.D.,417(55), 419(144), 428(144), 431-432(144),478,480 Rossel, J. B., 422(177), 480 Rossetti, G.P., 90(41), 183 Roughton, F.J. W., 147(171), 186 Rowley, G. L. A,, 383(2), 392-393(3), 396 (21,407 Rozhdestventskaya, L. M.,475(246), 482 Ruby, W.R., 168(237), 187 Rudakov, E. S., 413(6), 417-421(6), 428(6). 456-457(6),461,462,476 Rudin, E., 17

496

AUTHOR INDEX

Ruetschi, P., 418, 461,462,479 Rumpf, P., 1 6 , 2 9 Runge, F., 405(91), 410 Rupley, J. A., 384(19), 408 Rushton, B. M., 17 Russ, J. I., 91(51), 183 Russell, K. E., 141(168), 186 Rutejan, H. H., 385(26), 408 Ryan, J. J., 423(180), 481, 482 Sacconi, L., 417(60), 478 Saenger, W., 387(42), 389(59), 390( 60), 409 Sager, E. E., 16,29 Sager, W. F., 2(2m), 5(2m), 14,44(2), 50(2), 64(2m), 78, 82(8), 112-115(8), 121, 182, 418,421(124), 428(124), 457(124), 461 (124), 464,479 Salotto, A. W., 334(38), 377 Salvadori, G., 136(155), 185 Sampson. R. J., 418(128), 428(128), 461 (128), 479 Sandris, C., 90,91(49), 94,95(49), 100(49), 183 Sandstrom, J., 140-141(163), 186 Sano, K., 33 Santelli, M., 237, 238(89,90), 239,242,251 (89), 253(92), 265,299(150), 321. 322 Santelli-Rouvier, C., 223(73), 320 Santry, D. P., 334(45), 357(45), 377 Sapiro, R. H., 417(5 1,52), 478 Sapozhnikova, N. V., 418(106), 479 Sargent, G. D., 277(171),323 Sarma, V. R., 384(21), 408 Sasaki, T., 218,219(50), 227(50), 311(50), 320 Sasisekharan, V., 387(34), 408 Sastchenko, L. P., 405(94,98), 410 Satchell, D. P. N., 147(184), 186 Sauer, J. I., 1 1 1(146), 185 Saunders, V. R., 334(44), 3 7 7 Saunders, W. H., 419(146), 428(146), 480 Sauve, D. M., 191 Sawada, M., 23, 31(16), 39(16), 79 Sazhin, B. I., 418(104), 479 Schaleger, L. L.,415(11),477 Scheit, K.-H., 387(42), 389(54,56), 409 Scheit, K. W., 409 Scheraga, H. A., 385(26), 408 Scheurer, P. G., 147(172), 186 Scheutzow, D., 359(142,143), 360(143), 372(175), 379, 380 Schiavelli,M.D.,210(19,20),211,212,214 (20), 224(19,20), 260(130), 292, 308, 309(204), 3 10(203,204), 3 12(203,204), 318,319,322,324 Schimmel, P. R., 384,408 Schleyer,P. v. R., 157(210), 159, 161(218), 187, 240(98), 263(142), 264(148), 270 (142), 272-273(163,165), 274(163,167), 275-276(170), 279-280(175b), 281(176), 282,283-284(170), 288,291(189). 303 (170), 305(175b,176,177), 318,321-324 Schlitt, R., 34

Schmid, E. D., 2(5), 79 Schmid, H., 418(103), 479 Schmitz, E., 256(117). 321 Schnabel, W., 333(23), 376 Schneider, H. J., 264(147), 322 Schray, K. J., 407(106),410 Schreurs, I . W . H., 330(6), 360(6), 376 Schriesheim, A., 33 Schroder, G., 333(21), 376 Schubert, W. M., 259(126), 260, 261, 318, 322 Schug, I. C., 359(131), 379 Schulman, J . M., 335(53),377 Schultz, R. M., 396(74), 409 Schuster, I. I., 33 Schwab, G.-M., 417,418(48,103), 425, 456 (28), 457(27,28), 46 1-462(27,28,48), 477, 4 79 Schwamberger, E., 4 1 7 , 4 7 7 Schwan, T. C., 122, 124, 185 Schwartz, N., 417-418(56), 461(56), 478 Schwarzenbach, G., 17,212(24),319 Schweizer, M. P., 387(40), 409 Scorrano, G., 217(45), 319 Scott. F. L., 314(215), 325 Scott, I . M. W.,418-439(90), 461(90), 471 (231), 478, 482 Searles, S., 207-208(4), 318 Segal, G. A., 341(66), 346(66), 377 Seidl,H., 111(151), 185 Selier, P., 360(154), 379 Selivanov, V. F., 475(243), 482 Semeluk, G. P., 354( 108), 378 Servis, K. L., 240(96), 321 Severin, E. S., 405(94-98), 410 Seyferth. D. R., 321 Shannon, T. W., 90(44), 183 Shanshal, M., 277(172), 323 Shapiro, S. A., 417(72), 474(238), 478, 482 Sharma, R. K., 221(69), 320 Sharpe, A. N., 8 7 , 1 8 3 Shatenshtein, A. I., 80 Sheehan, I. J . , 321(62), 320 Shelton, E. M., 169(245), 187 Shelton, J . R., 109(95), 184 Shen, M. C., 122,185 Shenhav,H., 110(109), 120,184 Sheppard, N., 91(53), 93, 95(53), 101(53), 183 Sheppard, W. A., 2(6), 6(2c,2d), 9, 14(9), 16, 1 7 , 2 6 , 79, 85(25), 182 Sherman, Jr., P. D., 2 3 0 , 23 1,320 Sherrod, S. A., 264, 265-266(149), 269 (146,149), 322 Shida, T., 359(134), 379 Shillaker, B., 419(169). 480 Shiner, Jr., V. J., 292, 295, 310(208), 324, 325 Shorter, J., 59(36), 80, 414(9), 426(9), 464 (91,477 Shriner, R. L., 243(102), 321 Siewers, I. J., 406-407(105), 4 1 0 Silver. M . S., 398(76), 409 Simamura, O., 277(172), 323

AUTHOR INDEX Simon, L. N., 388, 389(50), 409 Simon, W., 6(6a), 29(4), 79, 91(54), 95(54, 61), 101(54), 147(61), 161(61), 183 Simonetta, M., 418(117), 456(117), 475 (245), 479,482 Sinev, V. V.,419(159), 480 Sinnott, M. V., 24,26(14), 40-41(14), 79 Skell,P. S., 39(19), 110-111(140), 126, 79, 185 Skinner, G.A., 152(198), 154(198), 186 Slade, M.D., 417(77), 421(77), 453(77), 456(77), 478 Sleeman, D. H., 335(54), 3 7 7 Sliwinski, W. F., 263(142), 270(142), 322 Slootmaekers, P. J., 417(78), 419(78,157), 423(157,182), 428(157), 453(78), 458 (157), 462(78), 464(218), 478, 480-482 Slotin, L., 388,409 Smid, J., 110(124), 124(124), 185 Smirnov, S. K.,34 Smirnov, Y. D., 34 Smith, D. E., 417(77), 421(77), 453(77), 456(77), 478 Smith, D. J., 147(189), 186 Smith, G. G., 9 , 2 3 Smith, N. A., 334(42), 3 7 7 Smith, S. L., 387(41), 409 Snell, J. M., 168(237), 187 Sobell, H. M., 387(38,39,43), 388(43), 408, 409 Soloman, I. J., 9, 61(8), 79 Sommer, F., 183 Sone, T., 398(76), 409 Sovers, O., 359(123), 378 Spaar, R., 266-269(151), 301(151),323 Spindler, E., 111( 149), 185 Spinner, E., 295( 199), 324 Sprecher, M., 323 Staeley, E. O., 405(99), 410 Stainbank, R. E., 359(130), 379 Stairs, R. A., 426(210), 481 Stamhuis, E. J., 207-208(5,6,7), 224(5,7), 318 Stanford, S. C., 141(166), 186 Stang, P. J., 268-269(152), 270,271(157), 274(167), 275-276(170), 281(176), 282, 283-284(170), 288,289,299(187), 292294, 301(157b), 303(170), 305(1756,176, 177), 307(186,193), 310,312(205),323, 324 Stangl, H., 111(150), 185 Stavely, H. E., 405(91), 410 Stefani, A., 110( 1 11,132), 121, 124( 11l), 184, 185 Steitz, T. A., 384, 385, 396(20), 408 St*ep;nek, V.,431(203), 481 Stepanyants, A. U., 5(8), 79 Stephani, R. A., 392,409 Sterner, J. H., 168 (237), 187 Stewart, R., 17, 33 Stock, L. M., 5(8), 82(4), 85(4), 112-116 (4), 79, 182 Stone, J., 426,481 Storch, H. H., 417-418(46), 461-462

491

(46), 477 Stothers, J. B., 24 Stout, C. A., 33 Streets, D. G., 334(48), 355(48), 3 7 7 Streitwieser, Jr., A., 17, 39-40(20), 50(28), 79, 183, 209(14), 270(155,156), 272 (159), 291(191),318, 323, 324, 343, 352, 356(106). 377, 378 Strepanova. R. N., 169(247). 174,187 Stromberg, A. G., 169(240), 1 8 7 Strominger, J. L., 403,404,405(85,92), 410 Struve, G., 393(72), 409 Sturm,H. J., 111(150), 185 Stubbs, F. J., 417(38), 422(38), 458(38), 4 77 Su,T. M., 263(142), 270(142), 322 Suck, D., 390(60), 409 Suhr, H., 33 Sukhorukov, B. 1.,418(113),463(113),479 Suld, G., 191 Sullivan, H. R., 405(91), 410 Summerville, R.,270,271(175b), 274(167), 279-280(175b), 281(176), 282(176,177), 288(177), 293(175b), 301(175b), 305 (175b,176,177), 323 Sundralinaam. M..387(36). 408 Sustmann, R.,'l l i ( 1 4 9 ) , i85,272-274(163, 165), 323 Sutton, L. E., 86,243(106), 321 Suzuki, S., 324 Swain, C. G., 2(2q), 12, 14,20,28, 31, 35, 44(2), 50(2), 78, 85, 150,182 Swallow, A. J., 333(22), 376 Swaminathan, R. S., 346(84), 378 Sweet, R. M.,404,410 Syrkin, J. K., 417,420(30), 461(30), 477 Szeimes, C., 111(147), 185 Szmant, H. H., 83,182, 191 Szwarc, M., 1 10( 111,123,125,130,131), 121, 124, 184, 185, 367(160), 372(173), 379, 380 Tabner, B. J., 330(8), 376 Tada, H., 388,409 Taft, R. W., 2(2f,Zi,2p,3-7), 3(2f,2p), 4(2f), 9, 12(7b), 14(10), 17,20(7b), 23,24,26 (2p), 29(2p), 33, 34, 38(10), 39(2i,4,10, 19,20), 40( 10,20), 41-42( lo), 44(2,23), 46(2p), 49(10), 50(2,28), 55(10), 58(32), 59(2p), 78-80, 82(3,11), 83, 85(26), 86, 108,109(97), 112(11), 120, 138(11), 147 (189), 150, 157,182, 184, 186, 208,240, 261,318, 322, 415(12), 417(12), 418 (131,132), 419(142), 427( 12), 428( 131, 132,142), 431-432(142), 457(131), 458 (12), 463,479, 480 Tait, J. M. S., 90(44), 183 Tal'rose, V. L.,418(105), 479 Talvik, A., 419(156), 424(156), 426(156), 428(156), 451(156), 480 Tanaka, J., 369(171),380 Tanida, H., 23,26(13), 33, 79 Tao, E. V. P., 215-216(40), 319

498

AUTHOR INDEX

Tatsukami, Y., 310(209), 325 Taubert, R., 354(109), 378 Tavale, S. S.,387, 388(43), 409 Taylor, D.,417(49), 477 Taylor, D. R., 220(54), 320 Taylor, H.T., 17 Taylor, R., 23 Tazawa, I,, 388,409 Tesoro, G.C.,1 lO(1 lo), 184 Thirtle, J. R., 168(237), I87 Thomas, B. H., 157,187 Thomas, C.W., 425(190), 457(190), 481 Thompson, G.,215-216(40),319 Thompson, H.W., 157,187 Tidwell, T. T.,85(24), 182 Tinker, H.B., 109(99), 184 Tirouflet, J., 9 Thorn, R. J., 418,419(161),428(125),440, 46 1,479-481 Threnn, R. H., 405(92), 410 Timm, E. W., 417(35), 422(35), 458(35), 477 Tigo, J., 348,378 Tipper, D. J., 403,404,405(85), 41 0 Todd, H.E.,110(133), I85 Tolles, W. M., 333(19), 376 Tolman, R. L., 388,389(50), 409 Toman, K., 347(87,88), 378 Tomilov, A. P.,34 Tommila, E., 23,33,417(42,43), 426(42, 43), 461(43), 467-468(228),474(240, 24 l), 477, 482 Tonellato, U., 284( 179,180), 285( 180,181 ), 286( 1 81-183), 287( 1 83,184),307( 1 82), 321,324 Toporishchev, G.A., 418(97), 423(97), 479 Topsom,R.D., 17,21(11),24,26,40-41 (14), 85(24), 79, 182 Toru, T., 218-219(50),227(50), 31 1(50), 320 Traynham, J. G.. 17 Tremper, H.S., 255(1 lo), 321 Trenner, N. R.,405(90), 410 Tribble, M. T., 17 TrinajstiC, N., 359( 15 1, 152), 379 Trischka, J. W., 418(95), 479 Trofimov, B. A., 423(185), 481 Trotman-Dickenson, A. F., 1 10(135,136), I85 Truce, W. E., 275,323 Tsang, J., 417(77), 421(77), 453(77), 456 (77),478 Tselinskii, I. V., 417(57,58), 423(57,58, 184), 426(57), 443(57), 445-446(57), 478. 481 Ts'o, P. 0. P., 387(40), 409 Tsubomura, H.,359(145), 379 Tsuda, Y.,392,409 Tsuji, T., 33 Tsuno, Y.,2(2g), 9,23,31,33, 34, 39,44 (2,231,50(2), 59, 78, 79, 210,215,319 Tsuruta, T., 124,185,318(219), 325 Tsvetkov, Yu. D., 418(108), 479 Tupitsyn, I. F., 419(140), 462( 140), 480

Turnbull, H. H., 164(223), 187 Turner,D.W., 351(103), 352,365(103),378 Ugi, I., 313(214), 325 Updegraff, I. H.,168(229), 187 Usher, D.A.. 389(58). 390,409 Van Boom, I. H., 222(7 l), 320 Vandenbelt, J., 16,29(7) Vandenberg, S., 16,29(7) VanDine, G.W., 161(218), 187,328(1),331 (11,376 VanOpstall, H. H., 17 Van Rysselberge, J., 426(199), 481 Vaughan, I., 6(lb), 16,17,23,29,61(6), 79 Vaughn, I., 426(195), 463(195), 481 Vdovina, L. V., 405(95), 410 VeEeTa, M.,6(6d), 29(4), 79, 475(242), 482 Velthorst, N. H.,359(150), 379 Venier, C. G.,334(34), 336(34), 338, 344 (34), 356,376 Verhoek, F. H., 9, 147(179), 186 Verhulst, I., 419(157),423(157),428(157), 458(157), 464(218), 480,482 Verkade, P. E.,2(2e,7), 3(2e), 44(2), 50 ( 2 e ) , 78 VessiAre, R., 241,321 Villars, D. S.,431(205), 481 Vinard, D. R., 154(206), 187 Vincow, G.,330(12), 376 Visco, R. E., 373(176,179),380 Vittum. P. W., 187(237). 187 Vizgert, R. V., 423(179), 481 Vladimitsev, 1. F., 169(240), 187 Voegtli, W., 95(63), 183 Voevodskii, V. V., 418(108), 479 Vogel, W., 61,95(64), 136(64), 147(64), 183 Volkenshtein, M. V., 420(172), 480 vanVoorst, J. D.W., 360(154), 379 Vos, A., 347(90), 378 M t t , V., 229(77-79),230(79), 231(77-79), 245(77,78), 247(78), 31 7 Vrbaski, T.,120, I84 Vuorinen, E.,474(240), 482 Wade-Jardetzky, N. G., 385(28), 408 Wadsi), I., 417(62), 419(141), 421(62), 453 (62), 456(62), 462(141), 478,480 Wagenhofer, H.,111(150), 185 Wagnihre, G.,328(3), 376 Walker, S., 86,183 Wall, J.S., 109(108), 120, 122(116), 184 Wall, L. A., 184 Wallbillich, G.,111(149), 185 Wallenfels, K.,169(241), 187 Wal1ing.C.. 110(138), 122(115), 184,185, 314, 315-316(216), 318,325 Wallis, E. S., 164(223), 187 Walsh, A. D.,343(77), 357(77), 377 Walton, D.R. M., 55(31), 58(31),80, 152 (198), 154(198), 186. 210(17), 214(36), 224( 17), 31 9

AUTHOR INDEX Walz, H., 33 Wang, C.-H., 466(222), 482 Wanless, G. G., 217(48), 220(48), 226-227 (48), 320 Ward,H. R . , 2 3 0 , 2 3 1 , 3 2 0 Wardell, J. L., 147(184), 186 Ware, J . C., 419(146), 428(146), 480 Waring, C. E., 417-418(40), 461(40), 4 7 7 Warren, C. H., 334(45), 357(45), 377 Warren, K. D., 359(147), 379 Wasilewski, J., 341(63), 359(125), 377, 379 Wassermann, A., 1 6 , 2 9 Watenpaugh, K., 387(37), 408 Watts, V. S., 91(55), 95(55), 101(55), 183 Weijland, W. P., 331(13), 333(13), 360(13), 3 76 Weinberg, A. E., 254(107), 321 Weisfeld, L. B., 147(188), 186 Weiss, J . , 324 Weissberger, A., 168(237), 1 8 7 Weitkamp, H., 161(217), 163,187 Wells, P. R., 2(2k,2p,3), 3(2p), 26(2p), 29 ( 2 ~ 1 ,33, 44(2), 4 6 0 ~ 150(2), , 59(2p), 78, 82(7,9,11), 112(7,9,11), 113(7,9), 114116(7), 138(11), 182 Weltin, E., 328(3), 376 Wenderung, J., 333(23), 376 Wenz, D. A., 138, 141(159), 185 Wepster, B. M., 3(2e,7), 3(2e), 6(3-5), 20 ( Z e ) , 23,29(2,3), 44(2), 50(2e), 78, 78 West, R., 152(200), 186 Westheimer, F. H., 59(33), 80, 390(62), 409 Westheimer, F. W., 291(191), 324 Westley, J., 383(3), 408 Whalley, E., 481 Wheland, G. W., 243(105), 321, 365(158), 3 79 Whipple, E. B., 349(97). 378 White, A., 393(70), 4 0 9 White, A.M., 137,185 White, J . E., 111(148), 185 White, W. N., 33, 34 Whitehead, M. A., 344(79), 377 Whiting, M. C., 257(118), 322 Whitney, R. B.,213(27),319 Wiberg, K. B., 368,379 Wieder, M. J . , 17 Wilcox, C. F., 5(8), 79 Wilkins, C. L., 270(156), 323 Willi,A. V., 9, 16, 17,29(6,7), 79, 418 (133),428(133), 463(133),479 Williams, E. G., 417(33), 4 7 7 Williams, E. J., 86, 183 Williams, J . E., 272-274(163,165),323 Williamson, K. L., 1 1 1(144), 185 Wilrnarth, W. K., 417-418(56), 461(56). 4 78 Wilson, Jr., E. B., 35 1 , 364-365(102),3 7 8 Wilson, E. R., 33

499

Wilson, I. B., 400(80), 409 Wilson, J. W., 232(81), 247(81), 310(208), 320. 325 Winkler, C. A., 417(34), 422(34), 448(34), 458(34), 4 7 7 Winstein, S., 33,261(133), 262,270(135, 155), 322, 323, 417(44), 426(44),477 Wissbrun, K. F., 147(173), I86 Witte, J., 33 Wittwer, Ch., 212(24), 319 Wohl, W. H., 8 6 , 1 8 3 Wojtkowiak, B., 153(201,202,204), 186, 187 Wold, S., 471(232,233,236), 472(236),482 Wolf, F. J., 405(90), 410 Wolfenden, R. W., 382(1), 4 0 7 Wolff, G., 466(223), 482 Wolfgang, R. L., 414-415(10), 477 Woodroff, H. B., 405(99), 4 1 0 Woodward, M., 359(124),378 Woodworth, C. W., 240(98), 321 Wrathall, D. P., 417(76), 421(76), 453(76), 456(76), 478 Yakhontov, L., 21(11), 79 Yamada, M., 257(119), 322 Yancey, J. A., 19 Yanovskaya, L. A., 169(247), 174,187 Yates, K., 33,214(34,35), 217(32,33), 225 (33), 272-273(164),319, 323, 325 Yogupolskii, L. M., 5(8), 79 Yonezawa, T., 272,323, 350(99), 378 Yoshinaga, K., 359(145), 3 7 9 Young, V. V., 405(91), 4 1 0 Young, W. G., 95(71), 183, 295(198), 324 Yukawa, Y., 2(2q), 23, 31, 33, 39,44(2),50 (2), 59, 78, 79, 2 1 0 , 2 1 5 , 3 1 9 Zahler, E., 48(26), 79 Zahradnik, R., 328(4), 331(14), 333(17), 338(58-61), 340(58), 341(58,64,68), 343 (59,76), 344(61), 346(68), 354(68,113), 355(113), 356(61), 358(118), 359(11,17, 58-60,142,143,153), 360(11,59,143), 361 (59,68), 362(59), 367(113), 368(118), 372(175), 374(68), 375(113), 376-380 Zalar, F. V., 160, 161(216), 1 8 7 Zandstra, P. J., 330(7), 359(150), 360(7), 376, 3 7 9 Zatsepina, N. N., 419(140), 462(140), 480 Zawidzki, T. W., 478(63-65), 453(63-65), 456(63-65), 4 7 8 Zeiss, G . D., 291(188),324, 328(1), 331(1), 3 76 Zollinger, H., 33 Zucher, L., 212(23), 319 Zuman, P., 167,188 Zutty, N. L., 124,185 Zweig, A., 373(178),380

Subject Index

Acetylene, electrophilic additions to, 215 Active-site-directed enzyme inhibitors, 402407 cephalosporins, 402-405 cycloserine, 405 penicillins, 402-405 a-phenylglycidic acid, 406 phosphonomycin, 405 Adenosine deaminase, 388 Alcohol dehydrogenases, 384 Alkylacetylenes, electrophilic additions to, 215 Alkylhaloallenes, solvolysis of, 309 Alkylvinyl systems, solvolysis of, 269 Alkynylcarbonium ions, spectral observations of, 295 Alkynyl ethers and thioethers, hydration of, 207 Allene, electrophilic additions to, 220 Allenes, substituted, electrophilic additions to, 221 Allenyl cations, 295 Amidines, 146 Anticompensation, 458,459 Arylacetylenes, electrophilic additions to, 2 10 Arylvinyl substrates, solvolysis of, 257 Bamford equation, 125 Biochemical processes, isokinetic behavior in, 418 Biradical, 328, 343 2-Bromo-l,3-butadienes, solvolysis of, 266 Calorimetric data, in the isokinetic relationship, 45 3 Carbenonium ions, 317 Carboxylic acids, 146 Catalysis, isokinetic behavior in, 417,457, 462 Charge transfer complexes, 108 Chemical equilibria, 344, 362, 366, 367, 369, 371 a-Chymotrypsin, 383, 384, 385, 396-402 Compensation, 416,458 Compensation factor, 421 Compensation law, 416 Conformal solutions, 461 Cooperative processes, 418,463 Coordinates, of the isokinetic relationship, 420-425 transformation of, 434,453 Correlation coefficient, 3

in the isokinetic relationship, 434-435, 453-454 Creatine kinase, 383, 392-396 Cyclopropylvinylsystems, solvolysis of, 264 Dewar Grisdale Equation, temperature dependence, 464 Diels-Alder reaction, mechanism of, 127 Dimerization, 363, 365, 366, 368, 375 Dipole moments, 86 Disproportionation, 342, 363, 364, 369, 370 Dual substituent parameter equation, 2 Electrical effect, composition of, 84 Electron affinity, 329, 351, 354 Electronic spectra, 333, 334, 343, 356 Electron spin resonance, 328, 333, 334, 342,348 Energy, activation, 414 potential, 415 zero-point , 415 Enthalpy, activation, 414 of diffusion, 418 external, 462 internal, 462 isokinetic, 468 reaction. 415 significance of, 466 of solution, 418 temperature variable, 470 of vaporization, 418 Entropy, activation, 414 external, 462 internal, 462 isokinetic, 468 reaction, 415 significance of, 466 temperature variable, 470 Enzyme kinetics, 383-384 computer analysis, 384 Enzyme specificity, 381-383,390, 396,407 product specificity, 382, 390, 396 substrate specificity, 382, 388, 390, 393, 396-402 Error slope, 433,469 Errors, of enthalpy, 432 of entropy, 432 of rate constant, 431 Extended Hammett equation, 83 Extrathermodynamic relationships, 41 6 temperature dependence, 463

501

502

SUBJECT INDEX

F measure of statistical precision, 3 F-test, for errors in kinetics, 431 for the isokinetic relationship, 441 Fructose 1,6-diphosphatase, 406-408 Glutamine synthetase, 384, 390-392 Hammett equation, 83 temperature dependence of, 426,463 Heat capacity, of activation, 472 of reaction, 472 Hydrogen bonding, 40, 51,418,463 Hydrophobic interaction, 419,461 Hypercompensation effect, 420,457 Inductive effect, 414-415 Infrared spectral frequencies, 97 Intermolecular interactions, 419,461 Ionization from ring position, 64 Ionization potentials, 90, 329, 338, 343, 35 1 Isoequilibrium relationship, 416 Isokinetic behavior, of ionization, 417 Isokinetic point, 473 Isokinetic relationship, 41 1 difinition of, 416, 419 derivation of, 460 examples of, 437,445,446,452,474-475 graphical representation of, 419 history of, 417 relation t o LFER’s, 463 statistics of, 428 Isokinetic temperature, 4 16, 45 6 calculation of, 423, 444,448,453 external, 462 meaning of, 457 reciprocal of, 42 1 values of, 457, 459, 474-475 variable, 472 Isoparametrical relationship, 4 19,472 Kirkwood-Westheimer equation, 176 LFER, temperature dependence, 416,463 Localized effects, field effect, 180 inductive effect, 180

366,370 INDO 346, 350 ’ of Longuet-Higgins and Pople, 335-338, 341, 345, 346,348, 354,357 MINDO, 342, 345,346 restricted, 334, 348 of Roothaan, 334, 335, 337, 340-342,352 SCF, 334, 335, 341, 370 SCF, convergence, 335 unrestricted, 334, 337, 346, 348, 350, 357 Multiple substitution, at nonequivalent sites, 173

Nitriles, dipole moments of, 157 Nmr chemical shift, of fluorine and carbon, 28, 35 of vinylidene protons, 93 Nmr of enzymes, 382, 385, 393,407 paramagnetic probes, 385 Nucleosides and nucleotides, conforrnationally restricted, 386-390 syn and anti conformations, 386-389 Olefin addition reactions, carbene addition, 108 Diel-Alder cycloaddition, 108 1,3-dipolar cycloaddition, 108 electrophilic addition, 108 nucleophilic addition, 108 radical addition, 108 Ortho substituent effects, 59 Oximes, 146 Partition function, 415 Penning ionization electron spectroscopy, 352 Peptidoglycan transpeptidase, 403-405 Phenols, aqueous pKa values, 50 Photoelectron spectroscopy, 334, 35 1, 352 Pi delocalization effect parameters, 3, 4, 13 interpretations of, 39 Pi electron demand, and p~ values, 45 Polynucleotide phosphorylase, 388-389 Positional dependence, of rho values, 59,62, 64 Preexponential factor, 414 Price-Alfrey equation, 122 Proximity effects, 97 Pyridones, 166

Mandelic acid racemase, 405-406 Meta substituent effects, 28 Minimal basis set, 3 Mixing coefficients, 2 Quartet state, 329, 341, 356 Molecular orbitals, degenerate, 328, 329 Quinones, 166 pairing properties, 360 singly occupied, 329, 336, 342, 348, 349, Radicals, anions, 329, 343, 360 352,354,358,377 cations, 329-333,343, 344,360 MO methods, ab initio, 334, 363, 364 conjugated, 329, 331, 343, 347, 348, 354, CNDO, 334, 341,342, 344, 346, 349, 354, 359,366, 367,370,374 357,368 geometries of, 343, 345 configuration interaction, 335, 338, 342, of hydrocarbons, 333, 338, 343, 354,358, 348, 356, 358 extended Htickel, 343, 346, 348,349, 359 methyl, 334, 338, 363 352, 368 pi, 328, 341, 348, 349 half electron, 336, 342, 345 HMO, 341,342,348,349,352,359, sigma, 328, 341, 348, 349

SUBJECT INDEX small, 343, 348, 356, 357 stability of, 334, 365, 366, 368, 369, 371 Reaction series, 414 classification of, 458 concept of, 427,463 examples of, 474-475 isoenthalpic, 458-459 is0kinet ic , 4 5 8-459 Reactivity, concept of, 414 Repulsion integral, 341, 352, 364, 271 Resonance effect, 414-415 Resonance effect parameters, 3, 4, 1 3 interpretations of, 39 Rho values, definition of, 2 UI, parameters, 4, 1 3 OR- parameters, 13, 24,42 UR (A) parameters, 1 3 , 4 3 OR+ (A) parameters, 4, 13, 42 UR parameters, 13, 31,43 rho values, solvent effects on,49 temperature dependence, 426,464 Ribonuclease, 389-390 RNA polymerase, 389 Root mean square, of data points, 3 of deviations, 3 Selectivity, within a reaction series, 460 Separation of I-R effects, 47 u* constants, 150 Solvation, quasi-crystalline, 46 1 Solvent effects, 415,458,461 on rho values, 42.49, 59 on sigma values, 40, 4 1 , 4 2 Spin densities, 338, 341, 342, 348, 349, 375 Statistical precision, f measure of, 3 Statistics, of the isokinetic relationship, 428 Steric effects, 98,414-415,458, 463 Steric parameter, 98 Substituent constants, 13, 85,426,463-465 Substituent effects, inductive, 414-415.458 mesomeric, 414-415.45s steric, 414-415, 458,463 cis-3-substituted acrylic acids, 99 trans-3-substituted acrylic acids, PKA of, 9 4

503

2-substituted acrylic acids, PKA of, 90 3-substituted propiolic acids, PKA of, 156 Substrate analogs, enzymes, eonformationally restricted, 381ff Swain and Lupton treatment, 1 2 , 8 5 Taft Equation, temperature dependence, 464 Transition-state analogs, enzymes, 404, 406 Triarylhaloallenes, solvolysis of, 308 Triplet state, 328, 353, 373 Tunnel effect, 418, 462 Vinyl cations, definition of, 205 deuterium isotope effects in generation of, 207,211,291 generation of, 206 hydride migration in, 2 19, 3 11 oxydation of vinyl radicals, 315 participation of allenyl bonds in the generation of, 237 participation of triple bonds in generation of, 229 primary, 313, 317 rearrangements of, 280 reduction of, 314 spectral observation of, 317 stabilities of, 316 stereochemistry of solvolysis, 276, 279 structure of. 271 theoretical calculations on the geometry of.. 272 -via diazonium ions, 254 Vinyl trifluoromethane sulfonates, preparation of, 275 solvolysis of cyclic, 275 ~~

X-ray diffraction, enzymes, 382, 384-385, 396, 398-399 Yukawa Tsuno Equation, temperature dependence, 464

Cumulative Index. Volumes 1 . 10

Acetals. Hydrolysis ox Mechanism and Catalysis for (Cordes) ..................... Acetronitrile, Ionic Reactions in (Coetzee) .................................................. Active Sites of Enzymes. Probing with Confonnationally Restricted Substrate Analogs (Kenyon and Fee) .............................................................. Barriers. to Internal Rotation about SingIe Bonds (Lowe) ........................... Benzene Series, Generalized Treatment of Substituent Effects in the. A Statistical Analysis b y the Dual Substituent Parameter Equation (Ehrenson, Brownlee, and Taft) ........................................................................... Carbonium Ions (Deno) ............................................................................... Carbonyl Group Reactions, Simple, Mechanism and Catalysis of (Jencks) ... Catalysis, f o r Hydrolysis of Acetals, Ketals, and Ortho Esters (Cordes) ....... Charge-Transfer Complexes. Reactions through (Kosower) .......................... Conformation, as Studied b y Electron Spin Resonance of Spectroscopy (Geske) ..................................................................................................... Delocalization Effects, Polar and Pi,an Analysis of (Wells, Ehrenson, and Taft) ......................................................................................................... Deuterium Compounds, Optically Active (Verbict) ...................................... Electrolytic Reductive Coupling: Synthetic and Mechanistic Aspects (Baker and Petrovich) ............................................................................... Electron Spin Resonance, of Nitrenes (Wasserman) ..................................... Electron Spin Spectroscopy, Study of Conformation and Structure by (Geske) ..................................................................................................... Electrophilic Substitutions at Alkanes and in Alkylcarbonium Ions (Brouwer and Hogeveen) ........................................................................... E n thalpy -Enthropy Relationship (Exner) ..................................................... Fluorine Hyperconjugation (Holtz) .............................................................. Gas-Phase Reactions, Properties and Reactivity of Methylene from (Bell) Group Electronegativities (Wells) ................................................................. Hammett and Derivative Structure-Reactivity Relationships, Theoretical Interpretations of (Ehrenson) ................................................................... Hydrocarbons, Acidity of (Streitwieser and Hammons) ............................... Hydrocarbons, Pyrolysis of (Badger) ............................................................ Hydrolysis, of Acetals, Ketals, and Ortho Esters, Mechanism and Catalysis f o r (Cordes) ............................................................................................... Internal Rotation. Barriers to, about Single Bonds (Lowe) ........................... Ionic Reactions, in Acetronitrile (Coetzee) .................................................. Ionization and Dissociation Equilibria. in Solution, in Liquid Sulfur Dioxide (Lichtin) .............................................................................................. Ionization Potentials, in Organic Chemistry (Streitwieser) ........................... Isotope Effecrs, Secondary (Halevi) ............................................................. Ketals, Hydrolysis oL Mechanism and Catalysis for (Cordes) ....................... Kinetics of Reactions, in Solutions under Pressure (le Noble) ...................... Methylene, Properties and Reactivity 05 from Gas-Phase Reactions (Bell) ... Napththalene Series. Substituent Effects in the (Wells, Ehrenson, and Taft) Nitrenes, Electron Spin Resonance of (Wasserman)...................................... Non-Aromatic Unsaturated Systems, Substituent Effects in (Charton) ........ Nucleophilic Displacements, on Peroxide Oxygen (Coetzee) ........................ Nucleophilic Substitution. a t Sulfur (Ciuffarin and Fava) ............................ Optically Active Deuterium Compounds (Verbict) ...................................... Organic Bases, Weak, Quantitative Comparisohs of (Arnett) ........................ Organic Polarography, Mechanisms of (Perrin) ............................................. Ortho Effect, Quantitative Treatment of (Charton) ..................................... Ortho Esters, Hydrolysis ox Mechanism and Catalysis for (Cordes) .............

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VOL . PAGE 4 4

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10 6

381 1

10 2 2 4 3

1 129 63 1 81

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147 51

7 8

189 319

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195 41 1

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1 1 45

1 1 1 4 5 2 6 8 10 4 6 7 1 3 8 4

75 1 109 1 207 1 147 319 81 45 81 51 223 165 235 1

5 06

CUMULATIVE INDEX. VOLUMES 1-10

Ortho Substituent Effects (Charton) ............................................................ Physical Properties and Reactivity of Radicals (Zahradnik and Carsky) ....... Pi Delocalization Effects. an Analysis of (Wells. Ehrenson. and Taft) ........... Planar Polymers. The Influence of Geometry on the Electronic Structure and Spectra of (Simmons) ......................................................................... Polar Delocalization Effects. an Analysis of (Wells. Ehrenson. and Taft) Polarography. Physical Organic (Zuman) ..................................................... Polyalkybenzene Systems. Electrophilic Aromatic Substitution and Related Reactions in (Baciocchi and Illuminati) ....................................... Protonated Cyclopropanes (Lee) .................................................................. Proton-Transfer Reactions in Highly Basic Media (Jones) ............................ Radiation Chemistry to Mechanistic Studies in Organic Chemistry. The Application of (Fendler and Fendler)........................................................ Radical Ions. the Chemistry of (Szwarc) ...................................................... Saul Winstein: Contributions to Physical Organic Chemistry and Bibliograph y ....................................................................................................... Semiempirical Molecular Orbital Calculations for Saturated Organic Compounds (Herndon) ..................................................................................... Solutions under Pressure. Kinetics of Reactions in (le Noble) ...................... Solvent Isotope Effects. MechanistfcDeductions from (Schowen) ............... Solvolysis. in Water (Robertson) .................................................................. Structure. as Studied by Electron Spin Resonance Spectroscopy (Geske) Structure-Reactivity and Hammett Relationships. Theoretical Interpretations of (Ehrenson) ................................................................................... Structure-Reactivity Relationships. Examination of (Ritchie and Sager) Structure-Reactivity Relationships. for Ortho Substituenfs(Charton) ......... Structure-Reactivity Relationships. in Homogeneous Gasphase Reactions (Smith and Kelley) .................................................................................... Substituent Effects. in the Napthalene Series (Wells. Ehrenson and Taft) Substitution Reactions. Electrophilic Aroma tic (Berliner) ........................... Substitution Reactions. Elec trophilic Aromatic in Polyalkybenzene Systems (Baciocchi and Illuminati) ........................................................... Substitution Reactions. Nucleophilic Aromatic (Ross) ................................ Sulfur. Neucleophilic Substitution a t (Ciuffarin and Fava) .......................... Thermal Rearrangements Mechanisms of (Smith and Kelley) ...................... Thermal Unimolecular Reactions (Wilcott. Cargill and Sears) ...................... Thermolysisin Gasphase. Mechanisms o f (Smith and Kelley) ...................... Ultra-Fast Proton-Transfer Reactions (Grunwald) ........................................ Vinyland Allenyl Cations (Stang) ................................................................ Water. Solvolysisin (Robertson) ..................................................................

. 235 327 147

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