70-14,050 KAUFFMAN, Karl Clinton, 1941- THE KINETICS OF BASE-CATALYZED ENOLIZATION OF 2-PHENYLCYCLOALKANONES AND CYCLOALKYL PHENYL KETONES. The Ohio State University, Ph.D., 1969 Ch emis t ry , organi c University Microfilms, Inc., Ann Arbor, Michigan THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED THE KINETICS OF BASE-CATALYZED ENOLIZATION OF 2-PHENYLCYCLOALKANONES AND CYCLOALKYL PHENYL KETONES DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Karl Clinton Kauffman, B.S., M.S, The Ohio State University 1969 Approved by Adviser Department of Chemistry PLEASE NOTE: Not original copy. Some pages have indistinct print. Filmed as received. UNIVERSITY MICROFILMS ACKNOWLEDGMENTS The author is deeply grateful to Dr. Harold Shechter for the suggestion of this problem, his interest and guidance during the course of the investi­ gation, and for his assistance in the preparation of this manuscript. Tho author wishes to express his appreciation to the Department of Chemistry of The Ohio State Uni­ versity for assistantship funds. He is deeply grateful to members of the staff for their cooperation, and to fellow graduate students for their help in numerous ways. XX VITA March 5, 1941 ............. Born, Dayton, Ohio 1 9 6 3 ...................... B.S., University of Dayton Dayton, Ohio 1963-1966 .................. Teaching Assistant, Depart­ ment of Chemistry, The Ohio State University, Columbus, Ohio 1 9 6 6 .......................M.S., The Ohio State Univer­ sity, Columbus, Ohio I 966-I969 .................. Research Assistant, Depart­ ment of Chemistry, The Ohio State University, Columbus, Ohio PUBLICATIONS H. W. Amburn, K. C. Kauffman, and H. Shechter, "Investi­ gation of Base-catalyzed Enolization of Cyclopropyl Ketones," J. Amer. Chem. S o c . , 91, 530 (I969). XIX CONTENTS Page ACKNOWLEDGMENTS .................................... ii VITA .......................................iii LIST OF T A B L E S ..................................... vi LIST OF FIGURES ................................... ix I. STATEMENT OF RESEARCH ....................... 1 II. HISTORICAL .................................. 4 III. RESULTS AND DISCUSSION ..................... 35 A. Bromination of 2-phenylcyclo- a l k a r . o n e s ........................... 35 B. Deuterium exchange of cyeloallcyl phenyl ketones ....................... 7I C. Deuterium exchange of 2-phenyl- cycloalkanones .................... 98 IV. EXPERIMENTAL .................................. IO6 Synthesis of 2-phenylcycloalkanones .... 106 General 1-Phenylcyclopentene 2-Phenylcyclopentanol 2-Phenylcyclopentanone semicarbazone 2-Phenylcyclopentanone 1-Phenylcyclohexene 2-Phenylcyclohexanone semicarbazone 2-Phenylcyclohcxanone Cinnamyl chloride Diethyl cinnamylmalonate Diethyl(3-bromo-3-phenylpropyl)malonate 2-Phenyleyclobutane-l,1-dicarboxylic acid 2-Phenylcyclobutanone semicarbazone 2-Phenylcyclobutanone iv CONTENTS (Continued) Kinetics of bromination of 2-phenylcycloalkanones .................. 120 General Kinetics of bromination Bromination of 2-phenylcycloalkanones Kinetics of deuterium exchange ........... 124 General Kinetics of deuterium exchange Deuterium exchange of cycloalkyl phenyl ketones Deuterium exchange of diisopropyl ketone Deuterium exchange of 2-phenylcyclo­ alkanones TABLES Table No. Page 1. Enol Content of Selected Ketones ........ 2.4. 2. Enol Contents of Cyclic K e t o n e s ........ %g 3. Effect of Solvent on Keto-enol Equilibrium of Ethyl Acetoacetate . 19 4 . Rates of Bromination of Alkyl Phenyl Ketones in 75% Acetic Acid— 0.5M Hydrochloric Acid at 2 5 ................ 20 5 . Acid-catalyzed Bromination of Cyclo- alkanones in 90^ Acetic Acid and Equilibria between Methylenecyclo- alkanes and 1-Methylcycloalkenes .... 21 6. Relative Rates of Bromination of Cyclo­ alkyl Phenyl Ketones in 90% Acetic A c i d ...................................... 23 7 . Bromination of 2-Phenylcycloalkanones in 90% Acetic Acid— 0.05M Hydrochloric Acid at 30° ............................. 24 8. Rates of Enolization and Ionization Equilibrium Constants of Some Ketones. 27 9 . Kinetic Acidities of Hydrocarbons Toward Cesium Cyclohexylamide at 50° .................................... 29 10. The Effect of Cation on the Position of Enolate Equilibria ....................... 3I 11. Base-catalyzed Rates of Deuterium Ex­ change of Cycloalkanones and Cycloalkyl Phenyl Ketones at 30 34 12. Data for Bromination of 2-Phenylcyclo- hexanone in Acetic Acid— Sodium Acetate at 30° ....................... 38 vi TABLES (Continued) Table No. Page 13. Effects of Sodium Acetate on the Kinetic Bromination of 2-Phenylcycloalkanones in Acetic acid at 3 0 ................... 4I 1 4 . Representative Data for Bromination of 2-Phenylcyclohexanone in 50^ Acetic Acid-0.5M Sodium Acetate at 45 .... 43 1 5. at 40° .... 45 1 6. at 30° .... 47 1 7 . Bromination of 2-Phenylcyclopentanone at 4 0 ................................... 49 1 8 . at 3 0 ................................... 51 19 . Representative Data for Bromination of 2-Phenylcyclopentanone in 50% Acetic Acid-0.5OM Sodium Acetate at 20 53 20. at 40° .55 21. at 30° 57 22. Representative Data for Bromination of 2-Phenylcyclobutanone in 50^ Acetic Acid-0.5OOH Sodium Acetate at 20° . 59 2 3 . Bromination of 2-Phenylcycloalkanones in 50% Acetic Acid-0.500K Sodium Acetate at Various Temperatures .... 6l 24 . Bromination of 2-Phenylcycloalkanones in 50% Aq. H0Ac-0.5M 0Ac“ Added .... 63 25. Deuterium Exchange of Cyclopropyl and Isopropyl Ketones in Dimethylformamide- Deuterium Oxide/Sodium Deuteroxide at 60° ...................................... 78 vii TABLES (Continued) Table No. Ease 26. Deuterium Exchange of Cyclopropyl and Isopropyl Ketones in Dimethylformaniide- Deuterium oxide/Sodium Deuteroxide at 60° .................................... 80 27. Représentât!'/e Data for Deuterium Exchange of Cycloalkyl Phenyl Ketones in 0.005M Sodium Deuteroxide/D„0- Diozane at 3 0 ........................... 90 28. The Rate Constants and the Relative Rates of Deuterium Exchange of Cycloalkyl Phenyl Ketones in Dioxane-Deuterium ^ Oxide/O.OOSM Sodium Deuteroxide at 30 • 91 29. Base-Catalyzed Deuterium Exchange in Dioxane-Deuterium Oxide using ^ 0.006m Sodium Deuteroxide at 47•5 . 93 3 0 . Ratios of Base-Catalyzed Hydrogen Exchange of Cyclopropyl and Isopropyl Ketones in Methanol with Sodium M e t h o x i d e ........................... 95 31. Deuterium Exchange of 2-Phenylcyclo- alkanones in 50% Deuteroacetic Acid- Deuterium Oxide-0.5M Sodium Acetate . 103 n i x FIGURES Figure No. Page 1. Typical data for bromination of 2-phenyl- cyclohexanone in acetic acid-sodium acetate at 3 0 .......................... 39 2. Bromination of 2-phenylcycloalkanones in 5OŸ0 acetic acid-sodium acetate at 30° .................................... 42 3. Typical graph of kinetic data for 2-phenylcyclohexanone in 50^ acetic acid-0.5M sodium acetate at 45 .... 44 4 . at 40° .... 46 5. at 30° .... 48 6. Typical graph of kinetic data for 2-phenylcyclopentanone in S0% acetic acid-0.5M sodium acetate at 40 . 50 7. at 30° . 52 8. at 20 . 84 9 . Typical graph of kinetic data for 2-phenylcyclobutanone in 50% acetic acid-0.5M sodium acetate at 40 . 56 10. at 30° . 58 11. at 20° .... 60 12. Bromination of 2-Phenylcycloalkanones in 50^ acetic acid-0.5M sodium a c e t a t e .................................. 62 XX FIGURES (Continued) Figure No. Page 13. The n.m.r..spectrum of diisopropyl k e t o n e .................................... 75 14. The n.m.r. spectrum of dicyclopropyl k e t o n e .................................... 76 15. The n.m.r. spectrum of isopropyl phenyl k e t o n e .................................... 77 16. Plot of kinetic data for deuterium exchange of isopropyl phenyl ketone in dimethylformamide-deuterium oxide at 6 0 ° ............................. 79 17. Plot of kinetic data for deuterium exchange of diisopropyl ketone in dimethylformamide-deuterium oxide at 60° 18. The n.m.r. spectrum of cyclopropyl phenyl ketone ........................... 82 19. The n.m.r. spectrum of cyclobutyl phenyl ketone ........................... 83 20. The n.m.r. spectrum of cyclopentyl phenyl ketone ........................... 84 21. The n.m.r. spectrum of cyclohexyl phenyl ketone ........................... 85 22. Typical plot of kinetic data for deuterium exchange of cyclobutyl phenyl ketone in dioxane-deuterium oxide-0.005M sodium deuteroxide at 30'' .................................... 86 23. Typical plot of kinetic data for deuterium exchange of cyclopentyl phenyl ketone in dioxane-deuterium oxide-0.005M sodium deuteroxide at 3 0 ° ................................. 87 X FIGURES (Continued) Figure No. Page 24. Typical plot of kinetic data for deuterium exchange of cyclohexyl phenyl ketone in dioxane-deuterium oxidc-0.OO5M sodium deuteroxide at 3 0 ° .................................... 88 25. Typical plot of kinetic data for deuterium exchange of isopropyl phenyl ketone in dioxane-deuterium oxide-0.005M sodium deuteroxide at 3 0 ° ............................... 89 XI I. STATEMENT OF RESEARCH Aldehydes and ketones having hydrogen atoms in positions alpha to the carbonyl groups are isomerized to enols by acids and converted to enolate ions by bases. Such processes are among the most important known to organic chemistry; however the theory of such processes is subject to conjecture and has been developed primarily in terms of electrical factors involving inductive and hyperconjugative effects.