Kinetics and Mechanism of the Solvolysis of cis- and trans-5,5-Dimethyl-1,J-cyclohexanediol Bis-~-toluenesulfonate in Aqueous Pyridine A Thesis Presented to the Faculty of the Sciences and Mathematics School Morehead State University In Partial Fulfillment of the Requirements for the Degree Master of Science in Chemistry by Louis Frederick Holzknecht May 1977 AP r'·l'\ ' I I"-.., __ ;,,- 1 /. - H'lb'J t, Accepted by the faculty of the School of Sciences and Mathematics, Morehead State University, in partial fulfillment of the requirements for the Master of Science degree . Master's Committee: Kinetics and Mechanism of the Solvolysis of cis- ~nd trans-5,5-Dimethyl-1,J-cyclohexanediol Bis-~-toluenesulfonate in Aqueous Pyridine Louis Frederick Holzknecht, M,S, Morehead State University, 1977 Director of Thesis: Dr, Lamar B, Payne Alkyl substituted and unsubstituted mono and bis­ arenesulfonates have been previously shown to undergo a retro Prins-like rearrangement in basic media. It was of interest to determine if this type of rearrangement extended to cis- and trans-5,5-dimethyl-1,J-cyclohexanediol bis-~­ toluenesulfonate,.and whether the rearrangement might be initiated by the Lewis base pyridine, The solvolyses of the cis- and trans-bistosylates in aqueous.-pyridine..: o.bey.e.cl..-pseudo.- f.irst~order -kinetics~. Typically,- rate differences-between the··-two -isomeric--bis­ tosylates solvolyzing at equal temperatures were on the order of 4-5 favoring the trans-bistosylate, Increasing the water concentration in the solvolysis medium resulted in a directly proportional increase in the reaction rate of the solvolysis, Calculation of thermodynamic parameters for the solvolyses of the bistosylates in 80% aqueous pyridine yielded the following data at 90°c, cis­ bistosylate, b.H*= 24,48 kcal/mole, b.s*= -12,J e,u,; trans-bistosylate, ~H*= 22.38 kcal/mole, ~s*= -14.9 e.u. No retro Prins rearrangement compounds were isolated from product studies conducted in 80% aqueous pyridine. Elimination and substitution products were isolated, and these compounds are thought to arise from a unimolecular mechanism. The basis for the unimolecular mechanism has been discussed. Aqueous pyridine may be more conducive to unimolecular substitution and elimination than to the retro Prins rearrangement. Accepted by: ACKNOWLEDGMENTS The author wishes_to acknowledge and to express his sincere appreciation to Dr, Lamar B. Payne for his suggestions, helpful criticism, and skillful guidance throughout this research; to Dr, Verne A. Simon and Dr, Charles A; Payne for their helpful suggestions and criticism; and to my colleagues, Bill Jones, Larry Kennard, and Nancy Tucker, for their suggestions, friendship, and moral support. A special thanks is due my wife, Molly, for her patient understanding and continuous moral support during this research and its five year interruption for my military service. TABLE OF CONTENTS Page LIST OF TABLES •. I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I ,I I I I I I I I I I V LIST OF FIGURES, • • I I I I I I I I I I I I I I I I I I I I I I I 1 1 1 I I I I I I I I I I I I vi INTRODUCTION, I I I I I I I I I I I I I I I I I I I I I· I 1 1 I I I I I I I I I I I I I I I I I I I 1 Chapter I, HIST9RICAL . ...•..•.....•. I I I I I I I I I I I I I I I I I I I I I I I I I 2 II. THEORETICAL •• I I I I I I I I I I I I I I I I I I I I I I I I 1 1 I I I I I I I I I I I 16 III. ElCPERilVIENTAL. I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 31 IV. DISCUSSION, I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 65 REFERENCES •• I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I I 82 APPENDIXES '.;• ~~ A. INFRARED SPECTRA, • •••••••••••••••••••••••••••••••• 85 B. NUCLEAR MAGNETIC RESONANCE SPECTRA, I I I I I I I I I I I I I I I 102 C. NOTES •.......•..• , • , ••••..••....•..••.. '■ •••••• , •• , 113 iv LIST OF TABLES Table Page 1. Solvolysis•Rate Constants •.••.•....•.•......•.•..•• 68 2, 'Thermodynamic Parameters •••••••.•••••••.••.••.••..• 78 V LIST OF FIGURES Figure Page 1. Kinetic plot for the cis-bistosylate in 90% pyridine-water at 90°e •.•.• ~•······•···•·•• 42 2. Kinetic plot for the cis-bistosylate in 85% pyridine-water at 90°e .•..••••••...•.•••••• 43 3. Kinetic plot for the cis-bistosylate in 80% pyridine-water at 90°c ..............•.... ,, 44 4. Kinetic plot for the cis-bistosylate _in 80% pyridine-water at 80°e, •.•• ,, •..••.••.••••• 45 5. Kinetic plot for the cis-bistosylate in 80% pyridine-water at 70°e ••••••..•••.••••.•... 46 6. Kinetic plot for the trans-bistosylate in 95% pyridine-water at 90°e .•••.•.••.••..•••.••• 47 7. Kinetic plot for.the trans-bistosylate in 90% pyridine-water at 90°c .....•............... 48 8, Kinetic plot for the trans-bistosylate in 85% pyridine-water at 90°e .•.•.•. ·.••.••••••.••• 49 9. Kinetic plot for the trans-bistosylate in Bo% pyridine-water at 90°e •••••.••.•.••..•.•••• ~o 10. Kinetic plot for the trans-bistosylate in 80% pyridine-water at 80°e .••.•••.•••••••..•. ,. 51 11. Kinetic plot for the trans-bistosylate in 80% pyridine-water at 70°e .•••••.••••••.•••••.• 52 12, Arrhenius plot for the solvolysis of the cis-bistosylate in 80% pyridine-water ••. .- ••••••••• 53 13. Arrhenius plot for the solvolysis of the trans-bistosylate in 80% pyridine-water •••••••.••• 54 14. Plots of rate constants versus H o concentration for cis- and trans-bistosylates •••••••••••••••••••2 79 vi INTRODUCTION The purpose of this study was to synthesize the ~-toluenesulfonates of cis- and trans-5,5-dimethyl-1,J­ cyclohexanediol, investigate the kinetics of their solvolyses in pyridine-water, and propose mechanisms for the reactions that occur, 1 CHAPTER I HISTORICAL · With the introduction of the Tipson method [1] for the preparation of arenesulfonate esters, new areas were opened to the synthetic and physical organic chemist. One interest­ ing field is the study of the chemistry of the arenesulfonate esters of alicyclic 1, J-diols, ·. particularly the 11-toluene­ sulfonate esters. In 1950, Clar.ke and Owen [2] investigated the chemistry of the arenesulfonate ·esters of cis- and trans-1,J-cyclohex­ anediol as an extension of earlier work with alicyclic 1,2 and 1,4 glycols [J,4]. In an attempt_ to prepare 1,J-epoxy­ cyclohexane (1), the mono-11-toluenesulfonate 2 underwent reaction with sodium methoxide in cold methanol. Instead of forming 1, the major product was J-cyclohexe~ol (J), the result of elimination. OH 1 2 3 2 J cis-1,J-Cyclohexanediol bismethanesulfonate in 5% aque­ ous sodium hydroxide gave 75% 2-cyclohexenol (4) and 1,4- _cyclohexadiene (5), both products of elimination. 0 4 5 Under the same reaction conditions, trans-bismethanesulfonate produced 28% of 4 and small amounts of 5 and 1,J-cyclohexa­ diene ( 6). 0 6 The bis-E-toluenesulfonates of cis~ and trans-1,J-cyclohexane­ diol ( 7, 8), under similar conditions,· would not react and were quantitatively recovered. Their lack of reactivity was attributed to insolubility. OTs OTs 7 OTs In 1952, Owen and Smith [5] investigated the arene­ sulfonate esters of cis- and trans-1,J-cyclopentanediol. It should be noted that Owen and Smith accepted Thiele's [6] configurational assignment for the isomeric 1,J-cyclopentane- 4 diols, Thiele was later shown to be in error, having re­ versed the actual configurations of the isomers [7,8,9,10]. In this paper, the correct configurational assignments are used. cis-1,J-Cyclopentanediol bistosylate (9) upon basic methanolysis gave as a major product cyclopentadiene (10) and what was tentatively identified as a mixture of the methoxy­ ·cyclopentenes 11A and 11B. TsO OTs Q 9 10 OMe- 11A 11B cis-Bismesylate 12, undergoing reaction in 5% aqueous po­ tassium hydroxide, produced 10, 46% 2-cyclopentenol (1J) and a small quantity of the original diol 14, 5 MsO OMs HO OH 12 HOO 14 13 Both the cis- and trans-bistosylates reacted similarly with potassium 11-nitrobenzoate in ethanol to produce 10 and the corresponding bis-11-nitrobenzoate derivatives. In 1957, Clayton, Henbest, and Smith [11] published the results of work which led to the preparation of a 1,J-epoxy­ cyclohexane derivative.' These workers reasoned that the 1,3- epoxide was not formed from 2, as expected by Clarke and Owen [2], because of the ease of trans diaxial elimination of the elements of I1""toluenesulfonic acid from the supposed highly unfavorable conformation 2A to produce J. OTs OH 2 2A To prevent inversion from occuring, a steroid system was chosen in which ring inversion was impossible. Thus, 5n­ hydroxycholestan-J~-yl mono-11-toluenesulfonate (15) under­ went .reaction with potassium tert.-butoxide in tert.-butyl , alcohol at 50°C to produce only two products: Jn,5~-epoxy­ cholestane (16) and 4,5-secocholest-J-en-one (17).