A STUDY OP THE KINETICS OP HYDROLYSIS OP CYCLOALKANONE DIALKYL KETALS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By WALTER THOMAS REICHLE, B.S. The Ohio State University 1958 Approved by: Adviser Department of Chemistry ACKNOWLEDGMENTS I I wish to express my deep apprecia­ tion for the guidance, help, and advice which I have received from Dr. Harold Shechter during the course of this investi­ gation. I am grateful to the General Electric Company and the National Science Foundation for fellowship funds. I also wish to thank the taxpayers of the State of Ohio and those of the United States of America for their liberal, indirect aid. ii DEDICATED To H.S.S. and My Wife, for the many lonely hours. iii TABLE OP CONTENTS Page I, INTRODUCTION ................................ 1 II. THE MECHANISMS OP THE HYDROLYSIS OF ACETALS AND K E T A L S ..................... 4 III. DISCUSSION OF RESULTS OF THE PRESENT INVESTIGATION ................. 19 The Kinetics of Hydrolysis of Homologous Cyclanone Dimethyl K e t a l s .......... 19 The Effect of the Alcohol Groups on the Rates of Hydrolysis of Cyciobutanone, Cyclopentanone, and Cyclohexanone Dialkyl Ketals ........ 33 The Effect of Alkyl Groups on the Rates of Hydrolysis of Methyl Ring-substituted Cyciobutanone, Cyclopentanone, and Cyclohexanone Dimethyl K e t a l s ......................... 43 Free Energy Relationships of Reactions of Cyclic Molecules .......... 58 IV, EXPERIMENTAL Constant Temperature B a t h ............... 6? Temperature Measurements ................. 68 Miscellaneous ............................ 69 Kinetic Procedure ....................... 71 Calculations .............................. 75 Special Calculations for the Hydrolysis of the Ten-membered Ketal . 77 Activation Energy and Entropy Calculations 78 Preparation and Purification of Chemicals . 80 Solvent Preparation . ................. 80 Catalyst Solutions . ................... 81 Solvent Densities ................. 82 iv • TABLE OP CONTENTS (Continued) Page IV. (Cont inued) Preparation and Purification of Ketones . 83 Cyclopentanone.............................. 83 Cyclohexanone .............................. 83 Cyclofteptanone.............................. 83 Cyclooctanone .............................. 83 Cyclononanone .............................. 83 Cyclodecanone .............................. 83 ®i-n-hexyl k e t o n e .......................... 85 3.3-Oimethylcyclopentanone ................. 85 3 .3-Difflsthylcyclohexaiion e ................. 85 2-Methylcyclopentanone ........... ..... 85 ©i-n-propyl ketone .......................... 85 Cyciobutanone .............................. 85 3 »3>5,5-Tetramethylcyclohexanone ........... 86 2-Methylcyclohexanone ..................... 86 2.2,^,4-Tetramethylcyclobutanone ........... 87 Cyclodecanone ....................... 9 Q Cyclododecanone ............................ 90 Cyclotetradecanone .......................... 90 Triisopropyl orthoformate ................. 91 Preparation and Purification of Ketals .... 92 General procedure illustrated with 2-fflethylcyclohexanone dimethyl ketal . 92 Cyclodecanone dimethyl ketal ............... 96 Cyclodecanone methyl enol ether ........... 97 2 . 2 , ^ , Tetramethylcyclobutanone dimethyl ketal ........ ........... 99 Cyciobutanone diisopropyl ketal ........... 99 Cyclotetradecanone dimethyl ketal ........ 99 APPENDIX A— Figures 7 through 1 5 ....................101 APPENDIX B— Infrared spectra of ketals . ......... Ill APPENDIX C— Tables: Numerical Data ............... 125 5 y LIST OP FIGURES Figure Page 1. Relative Rates of Reactions ............. 23 ( a , t> , c) 2. Conformations of Cyclodecane and Cyclodecane Cation ................... 31 3-5* Free Energy Plots 3* Cyclanone Ketsl Hydrolysis vs. 1-Ghloro-l-Methyl Cycloalkane Hydro lysis................................ 60 Cyclanone Ketal Hydrolysis vs. Cyclanoie Tosylate Acetolysis ............ 62 5. Cyclanone Cyanohydin Equilibrium vs. Cyclanone Ketal Hydrolysis .......... 63 6. Reaction V e s s e l ............................ 70 7-11 Activation Energy Plots for Hydrolysis of Cyclanone Dialkyl Ketals, etc............................... 102-106 A - A 12-15 Representative Plots of In ~ vs. Time for Hydrolysis 00 ^ Of Ketals ............................... 107-110 Infrared Spectra of Ketals ............... 112-124 LIST OF TABLES Table Page 1. Relative Rates of Hydrolysis of Various Dis.lkyl K e t a l s ................... 9 2. Relative Rates of Hydrolysis of Various Dialkyl Formale ................... 10 3* Ionization Constants of Cycloalkyl- carboxylic Acids in Water ......... 15 4. Ionization Constants of m-Cyclo- alkylbenzoic Acids in Aqueous Ethanol . 16 5. Reaction Velocity Constants and Relative Rates of Hydrolysis of Homologous Cyclanone Dimethyl Ketals ................. 20 6. Activation Parameters for Acid-Catalyzed Hydrolysis of Homologous Cyclanone Dimethyl Ketals ............................ 21 7. Activation Parameters of Hydrolysis of Cyclanone Dimethyl Ketals and Acetolysis of Cyclanol Tosylates..................... 3^ 8. Rates of Hydrolysis of Di&lkyl Ketals of Cyciobutanone, Cyclopentanone, and Cyclohexanone.......................... 35 9. Relative Rates and Activation Parameters for Hydrolysis of Dimethyl, Diethyl, and Dilsopropyl Ketals of Cyciobutanone, Cyclopentanone, and Cyclohexanone ......... 36 10. Relative Rates of Hydrolysis of Dialkyl Ketals of Cyclanones and Formaldehyde . 38 11. Hemiketal Equilibrium Constants of Cyclanones with Methanol and Ethanol . kZ 12. Rate Constants of Hydrolysis of Methyl-substituted Cyclanone Dimethyl K e t a l s .................................... Jji}. vii LIST OP TABLES (Continued) Table Page 13• Relative Rates of Hydrolysis and Kinetic Parameters of Methyl- substituted Cyclanone Dimethyl Ketals . 43 14. Relative Rates of Hydrolysis of Cyclic Ketals .............................. 46 15. Relative Rates of Hydrolysis of Methyl-substituted 1-Chloro- 1-Methylcyclohexanes ..................... 46 16. Relative Rates of Methyl-substituted Cyclanone Dimethyl Ketals ................. 4? 17. Relative Rates of Saponification of L a c t o n e s ................................ 48 18. Absolute and Relative Equilibrium Constants for Reaction of Ketone and hydrogen Cyanide ..................... 49 19. Absolute and Relative Equilibrium Constants for the Ketone-Alcohol- Hemiketal Equilibria ..................... 50 20. Rates of Hydrolysis of Open-Chained Diethyl Ketals and Acetals ............. 50 21. Physical Properties of Ketones ............ 84 22. Physical Properties of Ketals .............. 93 23-95 Numerical Data of Ketal Hydrolysis Reactions 126-198 viil INTRODUCTION In recent years much attention has been devoted to determining the properties of cyclic molecules. While a number of general rules exist which permit a qualitative estimate of some of the thermodynamic and kinetic proper­ ties more data are required to extend and refine the theo­ ries . The acid-catalyzed hydrolysis of ketals of cycla- nones (Equation 1), a reaction devoid of side reactions ii-i ORo R-k ^ 3 + H^O <EZ!zh c = 0 + 2RoOH (1 ) Hr2 '0B3 and rearrangements, has been studied in order to learn more about the kinetic properties of cyclic molecules. In this investigation the hydrolysis reactions were carried out at various temperatures in 66.7% (by w t .) 1 ,2-dimethoxyethane- 3 3 .3 ;? water (71.5 mole % water) mixtures, using dilute hydrochloric acid as catalyst. The kinetic entropies, enthalpies, and free energies were calculated from these data. The diethyl and diisopropyl ketals of cyciobutanone, cyclopentanone, and cyclohexanone have been hydrolyzed to determine the effect of the alcohol group of ketals on the reaction rates. 1 The rates of hydrolysis of the dimethyl ketals of cyciobutanone through cyclodecanone, as well as cyclodo- decanone and cyclotetradecanone, have been determined. For comparison two open-chained ketals— di-n-propyl ketone dimethyl ketal and di-n-hexyl ketone dimethyl ketal— have also been hydrolyzed. While considerable effort has been expended in determining the properties of homologous four- to seven- membered ring compounds, relatively little information is available concerning the kinetic and thermodynamic prop­ erties of cyclic compounds which have substituents in certain parts of the ring. Knowledge of these properties of substituted cyclic compounds xvould serve as a test of the current theories of reactivity of cyclic compounds and possibly place the theoretical ideas on firmer basis. In order to determine the effects of substituents on the kinetics of reaction of ketals of cyclanones, di­ methyl ketals of the following ketones have been hydrolyzed 2 ,2,4,4— tetramethylcyclobutanone, 2-methylcyclopentanone, 3 ,3 -dimethylcyclopentanone, 2-methylcyclohexanone, 3 j3 -bi- methylcyclohexanone, and 3 »3>5 ,5 -tetramethylcyclohexanone. Rate constants and kinetic parameters of these systems were thus obtained. Empirical free energy relationships (Hammett and Taft type) have become quite important in correlating many organic reactions. It was a further objective of the pres­ ent study to determine whether there is a free energy relationship between the hydrolysis of ketals of cycla- nones and other kinetic and thermodynamic properties of cyclic molecules; for example, the hydrolysis of 1-chloro- 1 -methylcycloalkanes and the acetolysis of cyclanol tosyl- THE MECHANISMS OP THE HYDROLYSIS OF ACETALS AND KETALS Acetals and.