3580mm f: ma ‘2}.r'azumm :Sm‘OPE EFFECTS i :f‘ij, m m 30mm 0;: gsosuwm m9 -. mm; cmms- . 3 :. :j: Thesisfonhepegree mm» ‘ MICHIGAN STATE UNIVERSITY ? ADAN A. EFFIO LEON. ‘ 1921 LIBRARY Michigan Stat: 3. University § This is to certify that the thesis entitled ‘Secondary 8 and y Deuterium Isotope Effects in the Solvolyses of Isobutyryl and Pivaloyl Chlorides presented by Adan A. Effio has been accepted towards fulfillment of the requirements for Ph . D . degree in Chemi § LIN 67.014444? Major professor Date August 24, 1971 0-7639 ABSTRACT SECONDARY 8 AND 7 DEUTERIUM ISOTOPE EFFECTS IN THE SOLVOLYSES 0F ISOBUTYRYL AND PIVALOYL CHLORIDES. By Adan A. Effio Leon In order to assess the usefulness of secondary deuterium isotope effects as mechanistic criteria and to understand better the mechanism of solvolysis of aliphatic acid chlorides, we studied the solvolysis of isobutyryl chloride and pivaloyl chloride. The rates of solvolysis of isobutyryl chloride were determined over a temperature range from -29.120° to -4.987° and acetone-water concentrations of 75% to 95%. Those of pivaloyl chloride were studied at temperatures from -l4.132° to +4.001° and acetone-water concentrations of 75% to 90%. The B isotope effects in the solvolysis of isobutyryl chloride decreased as the water concentration and temperature decreased, £43,, kH/kD (-24.985°) = 0.986 t 0.003 (75), 0.956 t 0.006 (90%); kH/kD (90%) = 0.955 t 0.007 (-29.120°), 0.987 t 0.008 (-4.987°). The y isotope effect was nearly temperature independent, g;g,, kH/kD (85%) = 0.964 t 0.006 (-29.120°), 0.971 t 0.0120 (-10.109°). kH/kD (95%) = 0.999 t 0.022 (-19.793°), 0.994 t 0.004 (-4.987°). It increased with decreasing polarity of the solvent, £43,, kH/kD (-15.6l6°) = 0.942 t 0.008 (80%), 0.999 t 0.003 (95%). The y isotope effect in the solvolysis of pivaloyl chloride followed the same trend; it was temperature independent and increased as the polarity of the solvent decreased, e;g,, kH/kD (-9.344°) = 0.909 t 0.004 (75%), 0.962 t 0.006 (90%); kH/kD (85%) = 0.943 t 0.004 (-l4.312°), 0.938 t 0.004 (+4.001°). The above inverse isotope effects indicate that isobutyryl chloride and pivaloyl chloride solvolyze primarily by a nucleophilic mechanism. This conclusion is further supported by examination of the rates of solvolysis (80% acetone-water, -15.10°) and the activation parameters for acetyl, propionyl, isobutyryl and pivaloyl chlorides which are reported in Table 1. TABLE 1. Rates of Solvolysis and Activation Parameters for a Series of Aliphatic Acid Chlorides. RC001 CH3C001 CH3CH2C001 (CH3)2CH0001 (CH3)3CCOC1 k 1 0.401 0.223 0.0395 rel. AH¢ (ca1/m) 14,240 1 50 13,822 i 80 12,755 i 123 13,326 i 99 AS* (e.u.) -12.2 t 0.2 -15.7 t 0.3 -21.1 t 0.5 -22.2 t 0.4 Evans1 and Kang2 suggested that acetyl and propionyl chlorides solvolyze by a dual mechanism (5N1 -SN2). The relative rates indicate that as 3 becomes more branched the reaction becomes more nucleophilic. This is also supported by the observation that the enthalpy of activation becomes less positive and the entropy of activation more negative. We conclude that isobutyryl chloride and pivaloyl chloride solvolyze predominantly by a nucleophilic mechanism. l. T. A. Evans, Ph.D. Thesis, Michigan State University, 1968. 2. U. G. Kang, M.S. Thesis, Michigan State University, 1970. SECONDARY B AND 7 DEUTERIUM ISOTOPE EFFECTS IN THE SOLVOLYSES 0F ISOBUTYRYL AND PIVALOYL CHLORIDES. By Adan A. Effio Leon A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1971 In the MEmory of My Parents Adan and Esther ii To Elva and Nena iii ACKNOWLEDGEMENTS I wish to thank Professor G. J. Karabatsos not only for the time and effort he has devoted contributing to my education, but also for suggesting this area of study and for his guidance and help during the course of this investigation. The financial assistance provided by the National Science Foundation and Michigan State University is gratefully acknowledged. iv TABLE OF CONTENTS INTRODUCTION .......................... EXPERIMENTAL .......................... II. KINETICS ....................... Preparation of Solvents .............. Conductance Apparatus ............... Conductance Cell ................. Measurement of Time ................ Constant Temperature Bath ............. Measurement of Temperature ............ Rate Determination ................ IDWI‘HDOWZD Treatment of Data ................. SYNTHESIS ....................... A. Isobutyric Acid .................. l. 2-Propanol-2g_ ................. 2. 2-Bromoporpane 2-g_ .............. 3. Isobutyric 2-g_Acid .............. B. Pivalic Acid ................... l. Pinacol-d12 .................. 2. Pinacolone-d —42 , ............... 3. Pivalic-g9 Acid ................ Page 16 16 16 16 16 16 17 17 17 17 18 18 18 19 19 19 19 19 19 III. IV. TABLE OF CONTENTS (Continued) PREPARATION OF ACID CHLORIDES ............. KINETIC RESULTS .................... RESULTS AND DISCUSSION ..................... I. MECHANISM OF ACID CHLORIDE SOLVOLYSIS ......... II. SOLVENT AND TEMPERATURE DEPENDENCE OF SECONDARY DEUTERIUM ISOTOPE EFFECTS ............... III. CORRELATION OF ACTIVATION PARAMETERS AND ISOTOPE EFFECTS ........................ IV. CONCLUSIONS ...................... BIBLIOGRAPHY .......................... vi Page 20 20 33 33 34 37 59 60 LIST OF TABLES TABLE I Secondary Isotope Effects in the Absence of Force Constant Changes at the Isotopic Position ....... II Secondary Isotope Effects Produced by Different Force Constant Changes at the Isotopic Position. . . . III Isotope Effects in the Solvolysis of trButyl Chlorides in 60% Ethanol at 25° ............ IV Isotope Effects in the Acidity of Carboxylic Acids . . V Isotope Effects in the Racemization of l,1'-Binaphtyl and its 2,2'-Dideutero Derivative in N,N'-Dimethyl- formamide Solution .................. VI Isotope Effects in the Reaction of Me-Pyridines and Mel ........................ VII Secondary 6 Isotope Effects in 95% Ethanol ...... VIII Isotope Effects of Substituted 1-Pheny1ethyl Chlorides in 50% Ethanol ....... . ....... IX Isotope Effects in the Trifluoroacetolysis of Isopropyl Tosylate .................. X Secondary y Isotope Effects in the Solvolysis of Norbornyl Brosylates ................. XI Temperature Independent Secondary Hydrogen Isotope Effects .................... XII Rates of Solvolysis of Isobutyryl-go, -g4, -96 Chlorides in Aqueous Acetone ............. vii Page 2 3 6 8 9 1O 12 13 14 21 TABLE XIII XIV XV XVI XVII XVIII XIX XX XXI XXII XXIII LIST OF TABLES (Continued) Page Rates of Solvolysis of Isobutyryl -g0, -g4, -g6 Chlorides in Aqueous Acetone ............. 22 Rates of Solvolysis of Isobutyryl -go, -g,, -g6 Chlorides in Aqueous Acetone ............. 23 Rates of Solvolysis of Isobutyryl -g0, -g4, '96 Chlorides in Aqueous Acetone ............. 25 Rates of Solvolysis of Isobutyryl -g0, -g4, -g6 Chlorides in Aqueous Acetone ............. 26 Rates of Solvolysis of Isobutyryl -g0, -g,, '96 Chlorides in Aqueous Acetone ............. 27 Rates of Solvolysis of Pivaloyl -go, -g9 Chlorides in Aqueous Acetone ............. 28 Rates of Solvolysis of Pivaloyl -d0, -d9 Chlorides in Aqueous Acetone ............. 29 Rates of Solvolysis of Pivaloyl ~90, -g9 Chlorides in Aqueous Acetone ............. 30 Rates of Solvolysis of Pivaloyl -g0, -99 Chlorides in Aqueous Acetone ............. 31 Rates of Solvolysis of Pivaloyl -g0, -g9 Chlorides in Aqueous Acetone ............. 32 Temperature Dependence of the 8 Secondary Deuterium Isotope Effects in the Solvolysis of Acetyl Chloride and Acetyluil3 Chloride ........ 38 viii TABLE XXIV XXV XXVI XXVII XXVIII XXIX XXX XXXI XXXII XXXIII XXXIV LIST OF TABLES Page Temperature Dependence of the B and y Secondary Deuterium Isotope Effects in the Solvolysis of Propionyl -d , 2, 2-92 and -3, 3, 3-13 Chlorides. . . 39 Temperature Dependence of the B and 7 Secondary Deuterium Isotope Effects in the Solvolysis of Isobutyryl-g0, -g_], 16 Chlorides ........... 40 Temperature Independence of the y Secondary Deuterium Isotope Effects in the Solvolysis of Pivaloyl-g0, g9 Chlorides .............. 41 Arrehenius and Transition State Theory Parameters for Isobutyryl-g0, -g4, -g6 Chlorides ........ 49 Transition State Theory Parameters for Isobutyryl- go, -d4, -96 Chlorides ................ 50 Activation Parameters Determined from the B and y Isotope Effects in Isobutyryl-d0, -d1, -d6 Chlorides ...................... 51 Transition State Theory Parameters for Pivaloyl- go, -gg Chlorides .................. 52 Arrhenius and Transition State Theory Parameters for Pivaloyl-g0, -g9 Chlorides ............ 53 Activation Parameters Determined from the Isotope Effects of Pivaloyl-g0, -g9 Chlorides ........ 54 Enthalpies of Activation for a Series of Aliphatic Acid Chlorides and Their Deuterated Analogs ..... 57 Entropies of Activation for a Series of Aliphatic Acid Chlorides and Their Deuterated Analogs ..... 58 ix FIGURE 1 LIST OF FIGURES Page Hamnett relations for p—substituted benzoyl chlorides in 40% ethanol and 60% ether .............. 35 Hammett relations for p-substituted benzoyl chlorides in 1% water and 99% formic acid ............. 35 Temperature dependence on the secondary B and y Deuterium isotope effects in the solvolysis of propionyl, isobutyryl and pivaloyl chlorides in 75% acetone-water ................... 42 Temperature dependence on the secondary B and y deuterium isotope effects in the solvolysis of acetyl, propionyl, isobutyryl and pivaloyl chloride in 80% acetone-water ............. 43 Temperature dependence on the secondary 8 and y deuterium isotope effects in the solvolysis of acety1,propionyl, isobutyryl and pivaloyl chloride in 85% acetone-water .................. 44 Temperature dependence on the secondary 3 and y deuterium isotope effects in the solvolysis of acetyl, propionyl, isobutyryl and pivaloyl chloride in 90% acetone-water ............. 45 Temperature dependence on the secondary B and y deuterium isotope effects in the solvolysis of acetyl and isobutyryl chloride in 95% acetone-water ...... 46 III '11] \IIIII 1 ll LIST OF FIGURES (Continued) FIGURE Page 8 Isokinetic relationship for acetyl, propionyl, isobutyryl and pivaloyl chloride in acetone-water concentrations of 75% to 95% .............. 47 xi INTRODUCTION Isotope effects are discussed within the framework of the Born - Oppenheimer approximation. Thus, the energy of motion of the electrons depends on the atomic number of the nuclei and the number of electrons, not on the nuclear masses. The electronic energy of the molecules can be calculated as a function of the relative position of the nuclei which will represent the potential energy surface for nuclear motion. Therefore potential energy surfaces for isotopic molecules are identical. Isotope effects are then nuclear mass effects resulting from the different energy of nuclear motion on the same isotope independent potential energy surface.“2 Exact equations (neglecting tunneling and transmission coefficient isotope effects) for the statistical mechanical formulation of kinetic isotope effects within the framework of transition state theory, in the harmonic approximation, have been derived by Bigeleisen3 and Melander.“ Two equivalent forms for the isotopic rate ratio are, briefly: kH/kD = MMI x EXC x ZPE kH/kD = 6*HL/U*DL x VP x EXC x ZPE Here kH/kD is the ratio of the isotope rate constants, MMI is the mass-moment of inertia term, EXC is the vibrational excitation term, ZPE is the zero point energy term, VP is the vibrational product term and ”*HL/V*DL is the isotopic ratio of the imaginary frequencies representing the motion along the reaction coordinate. Holfsberg and Stern have perfbrmed detailed calculations for SNl and 5N2 type reactionsfis6 Their results are shown in Tables I and II. Secondary Isotope Effects in the Absence of Force Constant Changes at the Isotopic Position. \\ $ * # _ T°K sxc ZPE k /k /v* L/v* L H D H D 100 1.131 0.957 0.957 0.997 300 1.131 0.932 0.985 1.000 2000 1.131 0.920 0.998 1.000 TABLE 11. Secondary Isotope Effects Produced by Different Force Constant Changes at the Isotopic Position. + s 9 - CH3CDZCH2X -—-——{;> [01130020112 ..... X] v HL/v DL - 1.016 kH/kD Force Constant Change 200° 300° 400° 500° fCH 4.5 to 4.2 md/A 1.229 1.152 1.105 1.044 fHCH 0.53 to 0.35 md/A 1.238 1.153 1.109 1.083 fccu 0.68 to 0.50 md/A 1.241 1.150 1.079 0.980 It can be concluded that in the absence of force constant changes the isotope effect comes entirely from the ratio of the imaginary frequencies; that if the f0rce constant decreases in going from the ground state to the transition state, the isotope effect will be normal; if the force constant increases, the isotope effect will be inverse. Isotope effects are generally recognized as evidence of force constant changes at the isotopic position between reactant and transition state. Most of the work in isotope effects is devoted to understanding the origin of force constant changes and elucidating the reaction mechanisms. At the present time secondary isotope effects are analyzed and discussed in term of hyperconjugation,7 inductive effects8 and non-bonded interactions.9 The extent to which hyperconjugation may be important in determining B deuterium isotope effects has been a matter of considerable controversy.10 However evidence favoring this postulate has been accumulated since then. Shiner and co-workers11 have studied the solvolysis of trbutyl chloride and ‘tybutyl -gq,-_2,-g3,-g6,-gg chlorides in 60% aqueous ethanol at 25°. Their results are reported in Table III. TABLE III. Isotope Effects in the Solvolysis of thutyl Chlorides in 60% Ethanol at 25°. Compound kH/kD kH/kD per 0 -_J 1.0922 1.0922 -g2 1.2016 1.096 -g3 1.3304 1.100 -gG 1.7095 1.102 g9 2.3275 1.103 They interpreted their results in terms of hyperconjugation, whereby the force constants associated with the B C-H bond are weakened in going from ground state to transition state. The isotope effect is nearly cumulative, increasing slightly with the number of deuterium atoms. The confbrmational dependence of the isotope effect was elegantly demonstrated by Shiner and Humphrey.12 They observed a very small inverse isotope effect in the solvolysis of the bridge deuterated bicyclooctane derivative I, where the C-0 bond is in the nodal plane of the developing "p" orbital at the reaction center. kH/kD = 0.986 t 0.01 k With deuteration at the 8 position as in II, where hyperconjugation is possible, the isotope effect kH/kD was 1.14. Transmission through a n bond was also demonstrated by Shiner and Kirz13 in the solvolysis of the chloropentyne derivative, III. C1 III The isotope effect, kH/kD = 1.092, was explained again in terms of hyperconjugation through the unsaturated linkage. Halevi preposed8 the "inductive effect" in order to explain secondary deuterium isotope effects. Due to the small anharmonicity of the Morse Potential and the shorter length of the C-0 bond over the C-H bond, the electron density of carbon should be greater in the C-0 than in the C-H bond. Thus, placement of a positive charge near the carbon should be stabilized more by the C-0 than the C-H. This argument predicts an inverse secondary isotope effect. This prediction, however, is the opposite of what is observed in both a and B secondary isotope effects. Streitwieser and co-workersl“ have observed an isotope effect, kH/kD = 1.15, in the solvolysis of cyclopentyl-lgftosylate, IV. A .T. I IV They ascribed this effect as arising predominantly from the change of a tetrahedral C-H bending vibration to an out-of-plane deformation in the transition state. Although the inductive effect explanation fails to explain the above isotope effects, it has been invoked to explain an impressive amount of experimental data. The dipole moments15 of N03, CD3N02, (CH3)3CD are 0.01 to 0.04 Debye larger than those of the corresponding protium compounds. In the N.M.R. the proton signals in -CH20 are shielded by 0.015 ppm relative to those of the methyl16 and the 19 F in -CF20 by 0.06 t 0.05 ppm relative to those of -CF2H.17 Streitwieser and Klein18 have measured the isotope effects in the dissociation of a series of acids: They are reported in Table IV. TABLE IV. Isotope Effects in the Acidity of Carboxylic Acids. Acid KH/KD CD3COOH 1.03 (C03)3CCOOH 1.04 C6DSCOOH 1.02 They also invoked the inductive effect to explain these isotope effects. It was previously stated that isotope effects may be used as a probe of force constant changes.6 What is not known is the nature of the force constant that is changed by the inductive effect. Bell and Crooks19 have performed a detailed calculation of the relative dissociation constants of HCO0H and DCO0H. Using fundamental frequencies for HCOOH, DCO0H, HCDO', 0000', they calculated an isotope effect of 1.09. This value is in excellent agreement with the experimental one of 1.084 determined by Bell and Miller.20 The authors concluded that the isotope effect was due not only to the C-H and C-0 stretching vibrations, but also to the two bending vibrations as well as to those arising from coupling of these vibrations. Kresge and Preto21 have interpreted the isotope effect on the equilibrium constant for the ionization of triphenylcarbinol to triphenyl cation, V, as inductive in nature. 130011 + H2504/CH3C00H : 0* + H 0 V They found KD/KH = 1.013 for the aatha_and mata_deuterated analogs and KD/KH = 1.008 for the paaa_analog. Streitwieser and Humphrey22 also invoked the inductive effect to rationalize the isotope effects in the protodedeuteration of a-a_toluene which was ring deuterated. Their findings of kH/kD at 50° per ring deuteration were: 1.024 (QEEDQ): 1.004 (mata), and 1.018 (para). Bartell suggested that secondary deuterium isotope effects are primarily due to non-bonded interactions. Because of the greater amplitude of the zero point vibrational motion of the C-H bond relative to the C-0 bond, the effective size of deuterium is less than that of the hydrogen; therefore, in reactions in which non-bonded repulsions increase in going from reactant to transition state deuterium substitution will lead to faster rates. The isotope effect found by Melander and Carter23 in the racemization of the biphenyl derivative VI, kD/kH = 1.19, in ethanol at -19.8° can be safely attributed to non-bonded interactions. 0 Br 0 0 H N Br 0 VI Carter and Dahlgreenz“ studied the racemization of l,l'-binaphtyl—2,2‘-a2, VII, the results of which study are shown in Table V. TABLE V. Isotope Effects in the Racemization of 1,1'-Binaphtyl and its 2,2'-Dideutero Derivative in N,N'-Dimethylformamide Solution. 1°1< kD/kH 330* cal/mole 337.20 1.14 . 0.03 87.8 . 17.8 330.77 1.14 . 0.02 89.0 . 11.7 323.85 1.14 . 0.01 84.3 . 7.3 316.33 1.15 4 0.01 91.1 . 7.1 309.18 1.18 . 0.02 104.8 . 11.0 302.43 1.17 . 0.02 98.4 . 10.3 VII By use of suitable non-bonded potential functions and reasonable assumptions the authors showed that uns inverse isotope effect arises from an increase of the f0rce constant of the in—plane bending C—H frequency in going from ground state to transition state. Brown and co-workers25 have studied the reaction of methylpyridines with methyl iodide. Their results are reported in Table VI. TABLE VI. Isotope Effects in the Reaction of Me-Pyridines and MeI. Pyridine kD/kH 4-Methy1-a3 1.001 t .003 3-Methy1-g_3 1.009 t .002 2-Methy1-<_i_3 1.030 t .003 2,6-dimethyl-g6 1.095 t .003 They explained the enhanced reactivity of the deuterated analog where methyl is at the "2? position as steric in origin. They also observed26 an inverse isotope effect, kH/kD = 0.92, in the reaction of 2,6-dimethyl- pyridine and BF3, but a negligible one in the reaction with 8H3. Brown has taken the extreme position that secondary isotope effects arise predominantly from non-bonded interactions. Karabatsos and co-workers27 have examined the relative contributions of hyperconjugation and non-bonded interactions to secondary isotope effects. They observed a small isotope effect (kH/kD = 1.029) in the solvolysis of 8-substituted naphthalenes, VIII. CD I'll-ll ‘IJ 1| .1 [)1] \‘I ‘1 1| ‘l I 10 They rationalized their results as steric in origin. Extensive calculations within the framework of Bartell's theory gave values of 1.07 and 1.18 when the dihedral angle, 0, between the ring and the COC1 planes was assumed to be 60° and 45°, respectively. In systems where hyperconjugation was possible, gag, CD3COC1, the calculated isotope effect, kH/kD = 0.98 at -22°, was lower than the experimental one, kH/kD = 1.62; in systems like (CD3)3CC1 the calculated isotope effect was 1.10 and the experimental one 2.39. This led the authors to conclude that, in systems where hyperconjugation was possible, less than 10% of the observed isotope effect is due to non-bonded interactions. Jewett and Dunlop28 studied 6 deuterium isotope effects to assess the relative contributions of non-bonded interactions to secondary isotope effects. Their results are reported in Table VII. TABLE VII. Secondary 6 Isotope Effects in 95% Ethanol. System kH/kD Ref. (C03)3CCH2C(CH3)2C1 0.983 28 CD3CH=CHCHC1CH3 1.132 28 CD3C5CC(CH3)2C1 1.095 13 The saturated system is known to react 20 times faster than afbutyl chloride and the inverse isotope effect can be rationalized as steric in origin; however, in the allylic and acetylenic systems, the normal isotope effect 11 is better interpreted as due to hyperconjugation through the unsaturated linkage. These results support Karabatsos' conclusion that, in systems where hyperconjugation is possible, non-bonded interactions are of secondary importance. Isotope effects have been used to help elucidate the mechanisms of solvolytic reactions. It has been suggested that a and 8 effects should be a useful criterion of the degree of nucleophilic participation by the solvent in the rate determining step, since 5N2 reactions showed effects near unity and SNl reactions showed effects around 1.14 per deuterium. Shiner and co-workers29 have recently reported the a and 8 deuterium isotope effects for a series of substituted l-phenylethyl halides. Their results are shown in Table VIII. TABLE VIII. Isotope Effects of Substituted 1-Pheny1ethyl Chlorides in 50% Ethanol. Substituent (kH/kD)a (kH/k0)8 p-Methoxy 1.157 1.113 p-Phenoxy 1.157 1.164 p-Methyl 1.157 1.200 p-Fluor 1.152 1.211 m-Methyl 1.151 1.222 None 1.153 1.224 p-Bromo 1.133 1.221 p-Nitro 1.098 1.151 12 The observation that the 6 effect is nearly constant for the different substituents was taken as evidence that the reaction proceeds by a limiting mechanism. The smaller isotope effects for the p-bromo and p-nitro compounds were interpreted in terms of some nucleophilic character of the solvolytic mechanism. These conclusions were corroborated by the 8 isotope effects. Streitwieser and Duff0rn studied the solvolysis of isopropyl tosylate30 in trifluoroacetic acid, a solvent of low nucleophilicity and high ionizing power31. Their results are shown in Table IX. TABLE IX. Isotope Effects in the Trifluoroacetolysis of Isopropyl Tosylate. Compound (kH/kD)a (kH/kD)B (CH3)2CDOTS 1.22 t 0.02 (CD3)2CH0TS 2.12 1 0.10 The a isotope effect is larger than the one reported by Mislow32 in the acetolysis of isopropyl brosylate at 70°, kH/kD = 1.12. From the results the authors concluded that the acetolysis reaction is characterized by a higher degree of nucleophilic solvent participation than the trifluoro- acetolysis one. Secondary isotope effects have been use as a criterion in elucidating the nature of the norbornyl cation. Schaeffer and co—workers33 have reported the B deuterium isotope effects for 2-norborny1 brosylate. They observed an isotope effect, kH/kD = 1.04, for the eaa_(lx) and 1.28 fer the endo (X) compounds. 13 DDS 085 IX X They interpreted the data in terms of the rate determining f0rmation of the non-classical norbornyl ion for the a§a_and of the classical ion for the endo. The y isotope effects, studied by a number of workers§“:35 are shown in Table X. TABLE X. Secondary v Isotope Effects in the Solvolysis of Norbornyl Brosylates. 0mm “mas D‘dq "dq KoAc-HoAca 1.09 4 0.03 - 1.11 . 0.01 - 0.98 . 0.01 - 0.99 4 0.02 80% EtOHa 1.09 t 0.01 1.11 . 0.01 1.00 t 0.02 0.97 1 0.01 b HOAc 1.097 t 0.011 1.082 1 0.09 1.021 t 0.012 0.998 t 0.009 aReference 34. bReference 35. These results were also interpreted as evidence for a non-classical ion fer the aaa_compound and a classical one for the gage. That the isotope effects f0r the aaa.series varies with the degree of substitution have been confirmed by a number of workers.35’37 I’ll III!" I ll" 14 Hakka and co-workers38 have studied the temperature dependence of the isotope effect in the solvolysis of t:buty1 chloride and tzbutyl-ag chloride in 50% ethanol 50% water mixture. They found that the isotope effect decreased from 2.542 at 5.686° to 2.086 at 55.686°. This decrease confermed closely to the expected approximation AAG* = AAH*. Leffek and co-workers39 on the other hand found an unusual temperature independence of the secondary isotope effects in the solvolysis of isopropyl methanesulfOnate (kH/kD = 1.54 from 5° to 30°), isopropyl tosylate (kH/kD = 1.54 from 6° to 30°) and isopropyl bromide (kH/kD = 1.31 from 40° to 70°). This temperature independence was shown to be due entirely to 005*. A reasonable explanation may be given either in terms of probable solvation differences, or in terms of the recent theoretical analysis of the temperature independence of some isotope effects carried out by Nolfsberg and Stern5. They showed that kH/kD could be virtually temperature independent for two compensating effects in the force constant changes. Their results are summarized in Table XI. TABLE XI. Temperature Independent Secondary Hydrogen Isotope Effects. (903)2CHX (003)20H ....... xa T°K kH/kD 250 1.4080 280 1.4110 300 1.4130 320 1.4151 340 1.4170 360 1.4188 aAssumed force constants changes fCH in CH3 4.8 to 3.5 md/A. ftorsion 0.15 to 1.0 md/A. fHCC in CH3 0.68 to 1.0 md/A. 0ne HCCC torsion coordinate was employed per methyl group. 15 The work described in this thesis deals with the temperature and solvent dependence of the isotope effects in the solvolysis of isobutyryl and pivaloyl chlorides and their deuterated analogs. It was undertaken in order to probe further into the usefulness of secondary isotope effects as mechanistic criteria especially after the findings by Evans“0 that the isotope effects in the solvolysis of acetyl chloride increase with increasing temperature and that of Kang"1 that some isotope effects in the solvolysis of propionyl chloride invert (inverse to normal) with increasing temperature. EXPERIMENTAL I. KINETICS A. Preparation of Solvents. Conductivity Water: Conductivity water was prepared, as described by Evans“0 by passing distilled water through a column containing a layer of Dowex l-X8 (anion exchange resin) and a layer of Dowex SON-X8 (cation exchange resin). Water treated in this manner had a specific conductance of l x 10'6 mho/cm. Conductivity Acetone: Acetone (Fisher Certificate A-18) was treated with 50 g of potassium permanganate and 0.5 g of sodium hydroxide, refluxed overnight and distilled. Acetone obtained in this manner had a specific conductance of l x 19"8 mho/cm. Mixed Solvents: Mixtures of acetone and water were prepared as described by Evans.I+O B. Conductance Apparatus. A Wayne Kerr conductance bridge (Model 8221) equipped with an autobalance Adapter (Model AA 221) and a PS 109 power supply unit was used fer all conductance measurements. C. Conductance Cell. The conductance cell used is described by Papaioannou.“2 0. Measurement of Time. A precision scientific electronic digital timer accurate to 1/100th of a minute was used. 16 17 E. Constant Temperature Bath. The bath used is described by Papaioannou. It was equipped with a stirring motor, a submersible magnetic stirrer, a relay, a thermal control, a heater and a Beckmann Differential Thermometer. Temperatures constnat to t 0.005° were obtained over a temperature range from -30° to +4°. F. Measurement of Temperature. The temperature was determined by means of a quartz thermometer (2801A Hewlett-Packard) accurate to t 0.010°. One hundred readings were taken from the Quartz Thermometer and the average temperature was corrected for linearity and for the deviation of the ice point. G. Rate Determinations. The conductance cell containing a teflon stirring bar was filled with 250 m1 of solvent, immersed in the bath, and allowed to attain the desired temperature by stirring for about 40 minutes. A drop of the acid chloride was then added and stirred for at least a minute to assure homogeneity. Conductance readings were taken over the first three half- lives and the infinity was obtained after 20 half-lives. The deuterated analogs were treated in the same manner. H. Treatment of Data. First order rate constants were obtained by a least squares solution of the integrated first order rate expression using PROGRAM RATE. 1n (Ca; Ct) = -kt + 1n C00 3.: Conductance at infinite time C Ct = Conductance at time t. 18 The uncertainty in the rate constant is the standard error 0. o = 2 “*1 4192/1141”2 Xi = observed rate I; = mean n = number of observations The uncertainty in the isotope effect, kH/kD, is the standard error 0, obtained from the expression _ 2 2 2 2 1/2 Three computer programs were used to determined the activation parameters. Aataag_calculates both Arrhenius parameters (lnk/T ya, l/T) and transition state theory parameters (1nk/T ya, l/T) by an iterative least squares method. ‘AKIIV_calculates activation parameters by a single least squares solution of 1nk/T ya, l/T and HANQ§_calculates AAH* and 085+ by a single least squares solution of ln kH/kd ya, l/T. II. SYNTHESIS. A. Isobutyric Acid. 1. 2-Propanol-2g5 Acetone, 50 g (0.86 mole), was added dropwise to a slurry of 10 g of lithium aluminum deuteride in 205 m1 of dry ether. After the reaction mixture was kept overnight, it was treated with 10% solution of sodiun hydroxide, as described by Fisher.“3 The yield of the alcohol distilled from the reaction mixture was 90%. 19 2. 2-Bromoprgpane 2:95 The above alcohol was cooled at -30° and 35 m1 of phosphorous tribromide was added dropwise. After the reaction mixture was completed, the bromide was distilled, washed with dilute sulfuric acid, dried over sodium sulfate and redistilled. The bromide was obtained in 70% yield.“1+ 3. Isobutyric ZegEAcid: The above bromide was added dropwise to 12 g of magnesium in 50 ml of ether. After refluxing for 6 hrs it was cooled to -50° and 20 g of dry ice was poured into the flask. When this attained room temperature, 20 m1 of 020 was added, the mixture was acidified and immediately extracted with ether. The acid was obtained in 30% yield. The same sequences were used for the preparation of isobutyric-a6 acid by starting with acetone-g6. The isotopic purity of the acids was checked by n.m.r. B. Pivalic Acid. 1. Pinacol-ng: Acetone-a6, 66 g (1 mole), and 13 g of mercuric chloride were added to 12 g of magnesium in 120 m1 of dry benzene. After the reaction was completed, 40 m1 of water was added, the solution concentrated to l/3rd of its volume and cooled in an ice bath. The yield of pinacol hexahydrate was 60 g.“5 2. Pinacolone-ngz The above pinacol was added to 250 ml of 6N sulfuric acid and distilled immediately. After being dried and distilled, 20 ml of pinacolone was obtained. 3. Pivalic-ag was added 38 ml of bromine at such a rate as to keep the temperature below 5°. Acid: To 750 ml of H20 and 85 g of sodium hydroxide The solution was then cooled at 0° and the pinacolone was added dropwise. 20 After refluxing for three hours the solution was then concentrated, acidified with sulfuric acid and extracted with ether. The yield of the acid was 7 g. The n.m.r. showed an isotopic purity of 97%. III. PREPARATION OF ACID CHLORIDES. ' The acids were prepared by the method described by Brown.“6 The method is described below. To a round-bottomed flask equipped with a vigraux fractionating column and standard distillation head was added 0.1 mole of the acid and 0.2 mole of benzoyl chloride. The acid chloride was distilled in an ice-cooled receiver as quickly as possible. The distillate was refluxed for 30 minutes to purge the hydrochloric acid. The distillation was repeated a second time, The yield was 70%. The isotopic purity of the deuterated acids was determined by n.m.r. IV. KINETIC RESULTS. The rates of solvolysis of isobutyryl chloride and isobutyryl-gJ, -96 chlorides are reported in Tables XII to XVII. The rates of solvolysis of pivaloyl chloride and pivaloyl-g9 chloride are reported in Tables XVIII to XXII. The average rate constants were used to determine the isotope effects in the solvolysis of isotutyryl chloride and pivaloyl chloride systems. 21 TABLE XII. Rates of Solvolysis of Isobutyryl-_O, -a4, ”g6 Chlorides in Aqueous Acetone. = -29.120 1 75% acetone k x 104 90 91 96 8.5745 8.7467 9.1765 8.5591 8.8079 9.1856 8.5712 8.7604 9.2185 8.5683 1 .0082 90 4.7480 4.7420 4.7417 4.7439 1 .0035 90 2.8891 2.8830 2.9046 2.9082 8.7717 1 .0300 80% acetone k x 104 91 4.9025 4.9026 4.8868 2.8962 1 .0148 00 1.6291 1.6289 1.6487 1.6356 1 .0114 4.8986 1 .0079 85% acetone k x 104 91 .0401 .0423 .0342 000000 9.1935 1 .0220 9., 4.9972 4.9520 5.0240 3.0388 1 .0043 90% acetone 1 R-C=0 + C19 + TEE—9 1100011 2. Nuc1eophi1ic + (3'12 r.d.s fast RCOC1 + H20 ————> M's-c1 ————> 1100011 0C) Johnston,‘+9 in reviewing the so1vo1ysis of aromatic acid ch1orides, a1so supports the idea of two mechanisms operating simu1taneous1y. A unified mechanism has been proposed by Evans.1+0 The activation process is depicted as: 33 34 RCOC1 + H20 _ \L + 7 9H2 0H2 ('1H + : R-C=0 é— R-C=0 <———> R-L-OQ —% R-C-OH c1 01 11 11 "L" "N" The transition state is shifted from “L" to "N" with decreasing so1vent po1arity. Evidence favoring this idea has been presented. In the so1vo1ysis of substituted benzoy1 ch1orides, the Hammett reaction constant, p, varies with the so1vent po1arity. So1vo1ysis in 40% ethano1 - 60% ether gives a straight 1ine Hammett p1ot with positive p.50 In 1% water-99% formic acid the substituent effect is comp1ete1y reversed, and a negative 0 is obtained.51 The p1ots are represented in Figures 1_ and 2, From the va1ues of p it was conc1uded that in the former reaction the so1vo1ysis of benzoy1 ch1oride goes predominant1y by a nuc1eophi1ic path and in the 1atter by a 1imiting path. IL. SOLVENT AND TEMPERATURE DEPENDENCE OF SECONDARY DEUTERIUM ISOTOPE EFFECTS. It is recognized that reactions that proceed by a 1imiting mechanism show 10% - 12% rate retardation upon isotopic substitution at the bgtg_ carbon. In bimo1ecu1ar disp1acement reactions the effect is near unity. Ca1cu1ations carried out by Mi11er52 predict an inverse isotope effect (kH/kD < 1) for reactions whose mechanism is nuc1eophi1ic with kH/kD increasing with temperature; and a norma1 effect (kH/kD > 1) for reactions 35 Log k/k0 FIGURE 1. Hammett re1ations for p-substituted benzoy1 ch1orides in 40% ethano1 and 60% ether. Log k/k0 FIGURE 2. Hammett re1ations for pfsubstituted benzoy1 ch1orides in 1% water and 99% formic acid. 36 whose mechanism is 1imiting, with kH/kD decreasing with temperature. However, there are certain reactions in the border1ine region whose mechanisms cannot be unambiguous1y c1assified as either 1imiting or nuc1eophi1ic. Saunders and co-workers53 studied the f0rmo1ysis and aceto1ysis of 2-pheny1ethy1 p-tquenesu1fonate, XII. In the f0rmo1ysis the B deuterium ¢CH CHZOTs 2 XII isotope effect was 1.17 and in the aceto1ysis 1.02. They interpreted the resuIts in terms of a predominant1y SN1 mechanism in the f0rmer so1vent and in terms of a border1ine SN1-SN2 mechanism in the 1atter so1vent. However, the sma11 isotope effect is not conc1usive evidence that the mechanism of the aceto1ysis is border1ine in nature; it may we11 be that, in view of the 10w ionizing power of the so1vent, the substrate is reacting exc1usive1y by a nuc1eophi1ic path. Evans”o studied the 8 isotope effect in the so1vo1ysis of acety1 ch1oride. His resu1ts are summarized in Tab1e XXIII. The decrease of the B isotope effect with decreasing so1vent poIarity was attributed to a dua1ity in mechanism, changing from 1imiting in high1y po1ar so1vents to nuc1eophi1ic in 1ess po1ar so1vents. In terms of a unified mechanism the transition state shifts from "L" to "N" with decreasing so1vent po1arity. The B and y isotope effects in the so1vo1ysis of propiony1 ch1oride were studied by Kang.“1 The resu1ts are summarized in Tab1e XXIV. The 8 effect was found to be near unity or inverse, depending on the so1vent. 37 He suggested that the compound so1vo1yzed predominant1y by a nuc1eophi1ic mechanism. He a1so supported the idea of a dua1 mechanism. The B and y isotope effects in the soIvo1ysis of isobutyry1 ch1oride and piva1oy1 ch1oride are summarized in Tab1es XXV and XXVI, respective1y. The 8 effect in isobutyry1 ch1oride indicates that it so1vo1yzes predominant1y by a nuc1eophi1ic mechanism. The decrease of this isotope effect with decreasing so1vent po1arity may be attributed either to an increase of the contribution of the nuc1eophi1ic path, or, in terms of a singIe unified mechanism, to a shift toward "N". In contrast to the B isotope effect, the y isotope effect in propiony1, isobutyry1 and piva1oy1 ch1oride increased with decreasing so1vent po1arity. The temperature dependence of the norma1 8 isotope effect of acety1 ch1oride was found by Evans to be unusua1, 143,, it increased with increasing temperature. Such behavior was not observed with the 8 effect in propiony1 and isobutyry1 ch1orides; they behaved norma11y. The y effect in propiony1, isobutyry1 and piva1oy1 ch1orides were found to be temperature independent. A p1ot of 109 kH/kD vs, 1/T in 75%, 80%, 85%, 90%, 95% acetone-water are reported in Figures 3:], In; CORRELATION 0F ACTIVATION PARAMETERS AND ISOTOPE EFFECTS. A serious prob1em concerning the interpretation and mechanistic app1ication of secondary deuterium isotope effects is our 1ack of understanding of the dependence of the isotope effects on the entha1pies and entropies of activation. As pointed out previous1y, Evans“0 and Kang“1 found isotope effects that either increased or crossed over (inverse to norma1) with increasing temperature. It is obvious, therefbre, that in such cases 38 TABLE XXIII. Temperature Dependence of the 8 Secondary Deuterium Isotope Effects in the So1vo1ysis of Acety1 Ch10ride and Acety1-g_3 Ch1oride. So1vent (Acetone-Hater) T°C kH/kD - 21.18 1.119 1 0.017 - 22.01a 1.106 1 0 006 - 25.37a 1.114 1 0.005 80% - 28.88a 1.105 1 0.043 - 31.32a 1.130 1 0.021 - 34.92 1.108 1 0 008 - 21.18 1.101 1 0.004 85% - 25.47 1.109 1 0.010 «-NOO Ln2100n - 9.54 1.070 1 0 010 - 15.72a 1.072 1 0 015 90% - 22.01a 1.059 1 0.002 - 28.88a 1.044 1 0.009 - 33.68a 1.026 1 0.010 - 0.20 1.030 1 0 007 - 9.55 1.018 1 0.004 95% - 15.51 1.018 1 0.004 - 22.62 1 008 1 0.001 - 25.47 1.004 1 0.004 aVa1ues determined by C. G. Papaionnou. 39 TABLE XXIV. Temperature Dependence of the B and y Secondary Deuterium Isotope Effects in the So1vo1ysis of Propiony1 -_0, 2, 2-d and -3, 3, 3-d Ch1orides. —2 -—3 So1vent (Acetone-Hater) T°C (kH/kD)B (kH/kD)Y 15.14 0.948 0.003 0.973 1 0.005 90% 10.56 0.965 0.007 0.988 1 0.005 5.53 0.967 0.005 0.990 1 0.005 .54 0.965 0.005 0.978 1 0.004 26.17 0.961 0.004 0.976 1 0.039 20.47 0.995 0.018 0.973 1 0.005 85% 15.54 0.978 0 005 0.976 1 0.005 10.57 0.985 0.004 0.977 1 0.007 30.58 0.989 0.007 0.976 1 0.010 25.41 0.998 0.010 0.976 1 0.005 80% 20.47 1.001 0.007 0.967 1 0.021 15.54 1.001 0.007 0.982 1 0.006 10.56 1.008 0.005 30.58 0.988 0.004 0.939 1 0.004 75% 25.55 1.008 0.007 0.960 1 0.005 20.55 1.011 0.005 0.957 1 0.005 40 'TABLE XXV. Temperature Dependence of the B and y Secondary Deuterium Isotope Effects in the So1vo1ysis of Isobutyry-gO -gq,-g6 Ch1orides. So1vent (Acetone-water) T C (kH/kD)B (kH/kD)Y 29.120 0 977 1 0.004 0 932 1 0.002 75% 24.985 0 986 1 0 003 0.919 1 0 003 20.004 0 988 1 0.009 0.924 1 0 008 29 120 0.968 1 0.002 0.951 1 0.007 24.985 0 968 1 0 009 0.942 1 0.003 80% 19.793 0.975 1 0 007 0.932 1 0 012 15.615 0.971 1 0 009 0 942 1 0 008 29 120 0.953 1 0.003 0.964 1 0.006 24.985 0.957 1 0.003 0.953 1 0.004 85% 20 004 0.970 1 0.004 0.948 1 0.003 15.616 0.965 1 0.007 0.955 1 0 012 10.109 0.978 1 0 008 0 971 1 0.012 29.120 0 955 1 0 007 0 986 1 0 007 24.985 0.956 1 0.006 0 996 1 0 005 20.004 0.963 1 0.004 0 970 1 0.002 90% 15.616 0.959 1 0.005 0.974 1 0.005 10.109 0 977 1 0.005 0.981 1 0 005 4.987 0.987 1 0 008 0.972 1 0.008 19 793 0.942 1 0.022 0 999 1 0 022 15.616 0.953 1 0 006 0.999 1 0 003 95% 10.109 0 967 1 0.016 0.995 1 0.017 4.987 0.978 1 0 005 0.994 1 0.004 41 TABLE XXVI. Temperature Independence of the 7 Secondary Deuterium Isotope Effects in the So1vo1ysis of Piva1oy1-d , d Ch1orides. 49 T°C So1vent 75% 80% 85% 90% - 14.312 0.906 1 0.003 0.927 1 0.002 0.943 1 0.004 - 9.344 0.909 1 0.004 0.927 1 0.002 0.941 1 0.003 0.962 1 0.006 - 4.978 0.901 1 0.018 0.923 1 0.008 0.942 1 0.003 0.964 1 0.004 - 0.255 0.925 1 0.005 0.944 1 0.006 0.959 1 0.003 + 4.001 0.919 1 0.007 0.938 1 0.004 0.959 1 0.003 241 16‘ to K" 9-0 "0 42 013C02C0C1 0 CD3CHZCOC1 X (CH3)2CD.C0C1 A (CD3)ZCHC0C1 B (CD3)3CC0C1 C x 103 -16 .. -24 q -32 1 4101 I 3.8 FIGURE 3. Temperature dependence on the secondary 8 and y deuteriUm isotope effects in the so1vo1ysis of propiony1, isobutyry1 and piva1oy1 ch1orides in 75% acetone-water. 43 c03coc1 o (013)2cpcoc1 1:1 501” cn3c02c001 x (003)2010001 o c03cnzcoc1 A (003)3ccoc1 A o 50 .. \0 o @\0'9\G 401» X 301- 20 1» 10 -~ K11 “9165 \ 1/1 x 103 X 103 0 I r 1 7‘ 1 t ‘1 3.7 3.8 3.9 4.0 4.1 4.2 A x \ -10 1» ‘“ °—‘-----——~~~ 1A~——__.__.---¢ ._._ B‘fl‘ 121 BR— -20 1 o r $ -30 -u- . A 140 ~— FIGURE 4. Temperature dependence on the secondary B and y deuterium isotope effects in the so1vo1ys1s of acety1, propiony1, isobutyry1 and piva10y1 ch1oride in 80% acetone-water. 1&4 CD3C0C1 O (CH3)2CDC0C1 E1 CH3CD COC1 X (CD3)2CHC0C1 0 5° 1" 0001 A (00 ) ccoc1 A CD3CH2 3 3 C) 40-« 3011 201* 1041 KM 1°94 3 1 A 1 1/T x 10 3 0 1 “0 3.7 3.8 3 9 x 4.0 4.1 -101. II ~20~~ A . ‘ A -30.- FIGURE 5. Temperature dependence on the secondary 8 and y deuterium isotope effects in the so1vo1ysis of acety1 propiony1, isobutyry1 and piva1oy1 ch1oride in 85% acetone-water. 445 0030001 0 (013)200coc1 8 01130020001 x (003)20110001 0 0030120001 A (6031300001 A 321— o 2411— o 151— 841— L0955 :0 1 1 1 L . 1/1 x‘103 x 10 0 3.7 3.18 3 9 410 41 41,2 0\A - 844 \ A 121 ‘ o . x h A! f 45.. A" " a h/‘i/r’ D B -241» X FIGURE 6. Temperature dependence on the secondary B and y deuterium isotope effects in the so1v01ysis of acety1, propiony1, isobutyry1 and piva1oy1 ch1oride in 90% acetone-water. 12. 8-4 4-1 “911— x 10 46 CD3COC1 O (C03)2CHC0C1 A (CH3)2CDC0C1 O - 4,+_ -12"" 1/T x 10 FIGURE 7. Temperature dependence on the secondary e and y deuterium isotope effects in the so1vo1ysis of acety1 and isobutyry1 ch1oride in 95% acetone-water. 447 .umo op am“ we mcovpneucmucou emu631ocoumum cw mv_gopgu Pxo—m>_q can pxcxuanOm? .pxcovaoga .quoum go» avgm:0wum—ms owuocwxomm .w mmaouu A=.QV#WQI 1 1... 1 1 .1 1 u q . . . op m a r.~p . e. 0 $1 4 #8 88841.13 .. 1 .uoozu~am=uv - m x “cm Puou~xumzo - N a 81 o as Booms - P .. 2 Agwuozuocopmuov acm>Fom 56215_18 usu< (atom/1931) *HV 48 mechanistic interpretations based on isotope effects measured at a sing1e temperature are meaning1ess. The possibi1ity that an isokinetic re1ationship for some secondary isotope effects may exist requires carefu1 scrutiny. Leff1er,5“ in studying the re1ationship between AH* and AS*, stated that in re1ated reactions invo1ving moderate changes in structure or so1vent the entha1pies and entropies vary, but not independent1y, This effect has been ca11ed the isokinetic re1ationship: AHT = 885* Here, 8 is the isokinetic temperature where a11 rates or equi1ibrium constants are the same within the precision of the re1ationship. Severa1 workers5515‘5'58 have pointed out that 1arge errors in AH* and 05* may 1ead to 1inear re1ationships. Thus, an apparent straight 1ine p1ot of AH4 vs, AS* does not necessari1y prove the existence of an isokinetic re1ationship. The activation parameters, AH*, 85*, and AAH*, for isobutyry1 ch10ride are reported in Tab1es XXVII, XXVIII and XXIX, respective1y. Those for piva1oy1 ch10ride are summarized in Tab1e XXX, XXXI and XXXII. A p1ot of AH+ vs, AS* for a series of a1iphatic acid ch10rides is shown in Figure 8. A fair1y 1inear corre1ation is obtained, a1though comp1ex behavior of AH* vs, 85* p1ots with so1vent variation has not been uncommon. Winstein and Feinberg59 showed that in the so1vo1y5is of _t_-buty1 ch10ride in various binary so1vent mixtures, a p1ot of AH* vs, 85* gives rather comp1ex curves. Tomi1a60 and Hine61 have a1so reported a comp1ex pattern of AH+ vs, AS+ with so1vent composition. TABLE XXVII. 49 for Isobutyry1-d0, -d1, "d6 Ch1orides. Arrehenius and Transition State Theory Parameters So1vent Parameter -—0 g4 g6 A x 10'9 3.53 1 1.36 2.58 1 1.03 4.81 1 1.85 75% Ea 14089 1 190 13945 1 190 14203 1 190 58* 13594 1 190 13450 1 190 13709 1 190 15* -16.48 1 0.76 -17 03 1 0.75 -15.87 1 0.76 A x 10'8 3.53 1 0.86 3.35 1 0.83 4.81 1 1.85 80% Ea 13253 1 123 13212 1 123 13356 1 123 An* 12755 1 123 12714 1 123 12858 1 123 55* -21.08 1 0.49 -21.18 1 0.49 -20 55 1 0.49 A x 10'7 7.84 1 1.33 5.89 1 0.99 7.83 1 1.32 85% Ea 12751 1 85 12599 1 85 12740 1 85 AH* 12258 1 85 12096 1 85 12237 1 85 15* -24 09 1 0.34 -24.65 1 0.34 -24.09 1 0.34 A x 10'6 8.59 1 1.08 6.32 1 0.79 1.04 1 0.13 90% Ea 11970 1 64 11797 1 54 12058 1 64 5H* 11460 1 64 11288 1 64 11549 1 64 55* -28.50 1 0.25 -29.11 1 0.25 -28.12 1 0.25 A x 10‘5 5.35 1 1.23 3.09 1 0.72 6.02 1 1.38 95% Ea 11054 1 119 10747 1 119 11111 1 119 AH* 10536 1 119 10229 1 119 10593 1 119 55* -34 05 1 0.46 -35.15 1 0.46 -33.82 1 0.45 50 TABLE XXVIII. Transition State Theory Parameters for Isobutyryl-go,-gq,-d Chlorides. _6 a Soivent Parameter d0 d1 d6 1H* 13584 1 54 13439 1 10 13698 1 139 75% 15* - 16.59 1 0.21 - 17.05 1 0.04 - 15.88 1 0.56 1H* 12744 1 144 12712 1 143 12849 1 202 80% 15* - 21.09 1 0.58 - 21.16 1 0.57 - 20 55 1 0.81 1H* 12254 1 127 12092 1 112 12233 1 163 85% 15* - 24.07 1 0.50 - 24.64 1 0.44 - 24 07 1 0.64 1H* 11459 1 104 11286 1 89 11546 1 87 90% 15* - 28.48 1 0.41 - 29.09 1 0.35 - 28.10 1 0.34 1H+ 10535 1 224 10229 1 261 10594 1 230 95% 15* - 34.01 1 0.85 - 35.12 1 1.00 - 33.79 1 0.88 aValues determined from AKTIV program. 51 TABLE XXIX. Activation Parameters Determined from the B and y Isotope Effects in Isobutyryl-d , '94: -g6 Chlorides. Solvent 75% 80% 85% 90% 95% a 90 ' 91 11H* 148 1 36 47 1 27 163 1 29 184 1 32 308 1 52 115* 0.56 1 0.14 -0.13 1 0.11 0.57 1 0.12 0.51 1 0.12 1.10 1 0.19 a 111-11 11H* -109 1 90 -109 1 68 20.1 1 58 -87 1 47 -52 1 9 115* -0.59 1 0.36 -0.55 1 0.27 0.0 1 0.2 -0.38 1 0.18 -0.2 1 0.03 aValues determined by HANDS program. 52 TABLE XXX. Transition State Theory Parameters for Pivaloy1~g0, -d Chiorides. .9 Solvent Parametera do g9 111* 13359 1180 13443 1117 75% 15* -21.81 1 0.57 -20.29 1 0.44 111* 13325 1 65 13383 1 54 80% 15* -22.19 1 0.24 ~21.82 1 0.20 111* 12931 1 31 12950 1 23 85% 15* -24.76 1 0.12 -24.57 1 0.09 111* 12271 1 31 12316 1 26 90% 15* -28.59 1 0.12 -28.34 1 0.10 aValues determined by AKTIV program. 53 TABLE XXXI. Arrhenius and Transition State Theory Parameters for Pivaloyl- -gg Chlorides. a Solvent Parameter do da A x 10‘8 4.17 11.56 5.40 1 2.15 Ea 13882 1 209 13966 1 209 75% 111* 13359 1 209 13442 1 209 15* -20.84 1 0.8 -20.33 1 0.8 A x 10‘8 2.12 1 0.39 2.56 1 0.48 Ea 13858 1 99 13917 1 99 80% * 111 13326 1 99 13384 1 99 15* -22.22 1 0.37 -2l.85 1 0.37 A x 10‘7 5.82 11.08 6.40 11.07 E 13464 1 99 13483 1 99 85% 3* 1H 12932 1 99 12951 1 99 15* -24.79 1 0.37 -24.60 1 0.37 -5 A x 10 8.55 1 2.31 9.69 1 2.51 Ea 12808 1 145 12853 1 145 90% 111* 12270 1 145 12315 1 145 15* -28.79 1 0.37 -28.37 1 0.54 aValues determined by ACTENG program. 54 TABLE XXXII. Activation Parameters Determined from the Isotope Effects of Pivaloyl-go, -d9 Chlorides. Solvent 75% 80% 85% 90% 11H*a -77 1 61 -60 1 17 -23 1 19 -48 1 21 115* -0.48 1 0.24 -0.38 1 0.07 -0.20 1 0.08 -0.25 1 0.08 aValues determined by HANDS program. 55 Leffek and Matheson62 used plots of 11H* v§_115* per deuterium to distinguish between SNl and 5N2 reactions. The differences observed were ascribed to differences in the solvation of SNl and 5N2 transition states. Thornton and Kaplan63 f0und kH/kD = 0.88 at 5l° in the reaction of dimethyl and dimethyl-g6 aniline with methyl p—toluenesulfonate in nitrobenzene. They rationalized this result in terms of frequency changes arising from steric interactions. Within the zero point energy approximation the isotope effect in reactions in which non-bonded repulsions increase in going from ground state to transition state should arise from differences in the enthalpies of activation, with 1HD*-1HH* being negative. Leffek and Matheson62 studied the temperature dependence of this reaction, they found AHg-AH: = -l34 1 30 cal/mole and ASD*-15H* = -0.lS 1 0.09 cal/mole-deg. For reactions where non-bonded repulsions decrease in going to transition state, MEI-1H: ought to be positive. In the solvolysis of isobutyryl chloride 11H* is positive, but the contribution of 115* is not negligible. Except f0r 80% acetone-water, 115+ is also positive. Both 11H* and 115+ increase as solvent polarity decreases. In contrast to this, both 11H* and 115* are negative, except for 11H+ in 85% acetone-water, in the solvolysis of the y deuterated isobutyryl and pivaloyl chloride. However, this behavior of the y isotope effects was reversed in the solvolysis of propionyl chloride, where 11H* and 115* were found to be positive. In view of this complex behavior, it would be best to defer speculations on the solvent dependence of the y isotope effect until more work is done on other mechanistically less ambiguous systems. 56 Activation parameters have been used to describe the mechanisms of various solvolytic reactions. Schlager and Long5“ have suggested that entropies and enthalpies of acitivation might serve as a convenient criterion of mechanism. Substrates that react by a nucleophilic path should show more negative entropies of activation and less positive enthalpies of activation than those substrates reacting by a limiting path. The 1H* and 15* for acetyl, propionyl, isobutyryl and pivaloyl chlorides are reported in Tables XXXIII and XXXIV respectively. Two trends are observed: The enthalpies and entropies of activation decrease with decreasing solvent polarity. They also decrease in going from the less branched acetyl chloride to the more branched pivaloyl chloride. Theye results suggest that propionyl, isobutyryl and pivaloyl chlorides solvolyze predominantly by a nucleophilic mechanism. This conclusion is further confirmed by comparing the relative rates of solvolysis of these chlorides in 80% acetone-water at -lS.lD°. The results are as follows: CH3C0C1 CH3CH2COCI (CH3)2CHC0C1 (CH3)3CCOCl relt. l 0.40] 0.223 0.0395 57 mvp +l mFmNF mm +| memp mm +1 +1 13‘ ¢wmmp mom vam_ _uouumfimzuv AAA A ONNNF mm A Nmmm_ mm A mmmm. mom A mmmm_ om m_F A mmmo_ Am A mAmF_ mm A AmN~_ mm_ A mmm~_ 01F A moum_ 1m mF_ A mNNoF Am A mm~A_ mm A omom_ mm_ A AAANP 011 A omAm_ Am Foouzumfimxuv m__ A ommop Am A ooep_ mm A mm-_ mm, A mmkmp om_ A Ammm_ om AA A _mA~_ ___ A mumm_ _P_ A Ammmp NA_ A mmmmp mm MA A mmmm_ __A A 01mm, om A mmom_ NA, A Aommp mm _uoumzumzu F~_ A mmeF ___ A ommm_ om A N~1m_ _A_ A mm_AF om om_ A 1_m__ om_ A oFomp mop A Aomm_ om A mmNAF mm m _oou Io omp A Ammp_ omF A umwmp mo_ A 11mm_ om A OANAF om 111 A01 1mm Aom Am“ uAu< 11611 1:1 mmAA1o_;u qu< 5_Am;1__< Ao Am_1mm A .mmopmc< umumcmusmo com cowuo>wpu< 1o mmAQchpcm .HHHxxx m4mwpu< mo mmwaogucu .>Hxxx m4m > W :0 . C. Brown, M. E. Azzaro, J. K. Koelling and G. J. McDonald, 1919,, 88, 2520 (1966). G. J. Karabatsos, G. C. Sonnichsen, C. G. Papaionou, S. E. Sheppele and R. L. Shone, ibid,, 89, 463 (1967). J. G. Jewett and R. P. Dunlop, 191g , 90, 809 (1968). V. J. Shiner, Jr., N. E. Buddenbaum, B. L. Burr and G. Lamaty, 1219,, 90, 418 (1968). A. Streitweiser, Jr., and G. Alan Duff0rn, Tetrahedron Letters, 16, 1263 (1969). mm J. E. Nordlander,and N. G. Deadman, J. Amer. Chem. Soc., 90, 1590 (1968). K. Mislow, S. Borcik and V. Prelog, Helv. Chem. Act., 40, 2477 (1957). J. Schaeffer, S. Weinberg, and M. Dagani, J. Amer. Chem. Soc., 89, 6938 (1967). B. L. Murr, A. Nicken, T. Swartz and N. H. Nerstnink, ibid., 89, 1730 (1966). 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 62 J. Jerkunica, S. Borcik, and D. E. Sunko, ibid., 90, 1734 (1967). J. Jerkunica, S. Borcik and D. E. Sunko, Chem. Comm., 1488 (1968). J. Schaeffer, J. Foester, and M. Dagani, J. Amer. Chem. Soc., 90, 4497 (1968). L. Hakka, A. Queen and R. E. Robertson, ibid., 87, 161 (1965). K. T. Leffek, R. E. Robertson, and S. Sugamury, Can. J. Chem., 39, 1989 (1961). T. A. Evans, Ph.D. Thesis, Michigan State University, 1968. U. G. Kang, M. S. Thesis, Michigan State University, 1967. C. G. Papaioannou, Ph.D. Thesis, Michigan State University, 1967. L. Fieser and M. Fieser, Reagents for Organic Chemistry, John Wiley and Sons, Inc., New York, 1968, p. 583. A. Murray, III, and 0. Lloyd Williams, Organic Synthesis with Isotopes, Interscience, New York, 1958, Vol. 2, p. 1482. H. Gilann and H. Blatt, Organic Synthesis, John Wiley and Sons, Inc., New York, Eleventh printing 1967, V01. 1, n1 459, 462, 526. H. C. Brown, J. Amer. Chem. Soc., 60, 1325 (1938). M. L. Bender, Chem. Rev., 60, 53 (1960). V. Gold, J. Hilton and G. E. Jefferson, J. Chem. Soc., 2756 (1956). S. C. Johnston, "General Base and Nuc1eophi1ic Catalysis", Advances in Physical Organic Chemistry, Vol. 5, V. Gold, ed. Academic Press, London, 1967. G. E. Branch and A. C. Nixon, J. Amer. Chem. Soc., 58, 2499 (1936). E. W. Grunden and R. F. Hudson, J. Chem. Soc., 501 (1956). 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 63 S. I. Mi11er, J. Phys. Chem., 88, 978 (1962). W. H. Saunders, Jr., 5. Aspenger and D. H. Edison, J. Amer. Chem. Soc., 88, 2421 (1958). a. E. Leffler, 0. Org;_Chem., gg, 1202 (1955). J. E. Leffler and E. Grunwald, "Rates and Eguilibria gf Organic Reactions", John Wiley and Sons, Inc., New York, N.Y., 1964, Chap. 9. C. D. Ritchie and W. F. Sager, "An Examination of Structure- Reactivity Relationship", Progress in Physical Organic Chemistgy, 8888m8, A. Streitweiser Jr., and R. W. Taft, ed., Interscience, 1965, p. 323. R. C. Peterson, J. Org. Chem., 88, 3133 (1964). O. Exner, Ngtgrg, 881, 488 (1964). 5. Winstein and A. H. Fainberg, J. Amer. Chem. Soc., Z8, 5937 (1957). E. Tomi1a, Acta Chem. Scand., 8, 975 (1955). a) J. B. Hyne, J. Amer. Chem. Soc., 88, 5129 (1960). b) 0. B. Hyde, R. Wills and R. E. Wonka, ibid., 88, 2914 (1962). c) J. B. Hyne and H. s. Golinkin, Can. 0. Chem., 181 125 (1968). K. T. Leffek and A. F. Matheson, ibid., 88, 439 (1971). E. 0. Kaplan and E. R. Thornton, J. Amer. Chem. Soc., 88, 6644 (1967). L. L. Schlager and F. A. Long, "Entropies of Activation and Mechanisms of Reactions in Solutions", Adv. in Phys. Org. Chem., 1211111 V. Gold, ed., Academic Press, London, 1963, p. 1.