A THERMODYNAMIC AND KINETIC INVESTIGATION OF B UNE FORMATION FROM ISOBUTYRALDEHYDE AND PRIMARY ALKYLAMINES A DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Francis Anthony Via The Ohio State University 1970 Approved by Advisor Department of Chemistry PLEASE NOTE; Some pages have small and indistinct type. Filmed as received. University Microfilms ACKNOWLEDGMENT I wish to thank Dr. Jack Hine for his patient guidance, informative discussions, and helpful suggestions during the course of this research. I wish to thank the appropriate government a- gencies and this Department of Chemistry for financial aid during the execution of this research. It is also appropriate to thank all my laboratory colleagues and other associates for their con­ structive influence. IX VITA November 50, 19^5 • .........Born, Frostburg, Maryland. June, 1961................... Graduated Beall High School, Frostburg, Maryland. June, 1965 ...................Graduated West Virginia Univer­ sity, Morgantown, West Virginia. September, I9 6 5 ............. Entered The Ohio State University as a Teaching Assistant August, 1 9 6 8 ................. • Received M.S. Degree, The Ohio State University, Columbus, Ohio. 1x 1 TABLE OF C0ETEBT8 Page ACKWOWLEDOyiENTS........................................ il VITA ............................................. ill LIST OF TABLES........................................ vi LIST OF FIGUEES....................................... x Chapter I. INTRODUCTION.................................. 1 II. HISTORICAL................................... 6 Kinetics of Imine Formation..................... Reported Bifunctional Catalysis................. Hydration of Isobutyraldéhyde................... The Micro-pKa’s of the Diamines................. III. EXPERIMENTAL.................................. 5 6 General............. ......................... IV. RESULTS . .................................. 46 Hydration of Isobutyraldéhyde................... Determination of the Micro-pKa Values of the Diamines Imine Formation................................ V. DISCUSSION...................................... 1 9 9 Hydration of Isobutyraldéhyde................... The Micro-pKa Values ................. Imine Formation.............................. iv TABLE OF CONTENTS (Cont'd.) Page VI. CONCLUSION . .............................. 230 APPENDIX ........................................... 231»- LITERATURE CITED...................................... 311 LIST OF TABLES Page 1. Estimated Structure of Monoprotonated N,N-Dimethyl- $4 ethylenediamine. 2. observed Rate Constants for the Hydration-Dehydration 48 Reaction. 3- Results for the Hydration-Dehydration Reaction with 52 Isobutyraldehyde. 4. Catalytic Constants for Hydration of Isobutyraldéhyde. 53 5 . Rate Constants for Dehydration of Isobutyraldéhyde 55 Hydrate. 6. Chemical Shift of Protonated Methylamine. 6l 7. Chemical Shift of Protonated Trimethylamine. 63 8. Chemical Shift of Protonated Triethylamine. 65 9 . Chemical Shift of Protonated n-Propylamine. 67 10. Chemical Shift of Protonated 2-Methoxyethylamine . 69 11. Chemical Shift of Protonated ,N'-Tetramethyl- ' 71 ethylenediamine. 12. Chemical Shift of Protonated N,H,H’,N’-Tetramethyl- 73 1,3 -propane diamine. 1 3 . Chemical Shift of Protonated H -Dimet hy let hylene- 75 diamine. 14. Chemical Shift of Protonated -Dimethyl-1,5-propane- 78 diamine. 1 5 . Chemical Shift of Protonated N-Dimethyl-1,4-butane - 8l diamine. 1 6 . Chemical Shift of Protonated H,H-Dimethyl-1,5-pentane- 84 diamine. Vi Page 17- observed and Estimated Chemical Shift Values. 88 1 8 . Evaluation of f for MesN( CHg)« 90 19* Micro-pKa Values for the Diamines. 92 20. Rate and Equilibrium Constants for the Reaction of 1Q5 n-Propylamine and Isobutyraldéhyde. 21. Equilibrium Constants for the Reaction of 3-Methoxy- 106 propylamine and Isobutyraldéhyde. 22. Rate Constants for the Reaction of 3-Methoxypropylamine 107 and Isobutyraldéhyde. 23 . Equilibrium Constants for the Reaction of 2-Methoxy- 109 ethylamine and Isobutyraldéhyde. 24. Rate Constants for the Reaction of 2-Methoxy ethyl- 110 amine and Isobutyraldéhyde. 2 5 . Equilibrium Constants for the Reaction of 2,2- 113 Dimethoxyethylamine and Isobutyraldéhyde. 2 6 . Rate Constants for the Reaction of 2,2-Dimethoxy- ll4 ethylamine and Isobutyraldéhyde. 2 7 . Equilibrium Constants for the Reaction of 2,2,2- , II6 Trifluoroethylamine and Isobutyraldéhyde. 2 8 . Rate Constants for the Reaction of 2,2,2-Trifluoro- 117 ethylamine and Isobutyraldéhyde. 2 9 . Equilibrium Constants for Formation of Carbinolamines II9 and Imines from Isobutyraldéhyde and Aliphatic Primary Monoamines. 3 0 . Evaluation of Linear Functions of the Form y = mx + d. 123 3 1 . Rate Constants for Monoamines. 125 3 2 . Equilibrium Constants for Imine Formation "with n,K- 132 Dimethylethylenediamine. 35- Equilibrium Constants for Carbinolamine Formation 135 ■with UjR-Dimethylethylenediamine. vii Page Rate Constants for Imine Formation with N,N-Dimethyl- 158 ethylenediamine. 55* Equilibrium Constants for Imine Formation with l4l Dimethyl-1,5 -propane diamine. 3 6 . Equilibrium Constants for Carbinolamine Formation l44 with Ef ,N-Dimethyl-1,3 -propanediamine. 31. Rate Constants for Imine Formation with -Dimethyl- l46 1,3 -propanediamine. 5 8 . Equilibrium Constants for Imine Formation with l48 Dimethyl-1,4-butanediamine. 39' Equilibrium Constants for Carbinolamine Formation 151 with N,N-Dimethyl-l,4-butanediamine. 40. Rate Constants for Imine Formation with E,E-Dimethyl- 155 1 .4-butanediamine. 41. Equilibrium Constants for Imine Formation with E,E- 155 Dimethyl-1,5-pentanediamine. 4 2 . Equilibrium Constants for Carbinolamine Formation 158 with E ,E-Dimethyl-1,5 -pent ane diamine. 4 3 . Rate Constants for Imine Formation with E,E-Dimethyl- 160 1 .5 -pentanediamine. 44. Calculation of Taft Substituent for Diamines. 162 45 . Calculation of Equilibrium Constants for Protonated l64 Diamines. 46. Equilibrium Constants of Diamines. I69 4 7 . Calculation of the Ionization Constants for Mono- 176 protonated Carbinolamine. 48. Estimation of the Ionization Constants for Protonated 178 Carbinolamines of the Diamines. 4 9 . Calculated Rate Constants for Imine Formation from 179 Isobutyraldéhyde and the Four Diamines. 5 0 . Greatest Percent Contribution of Each Rate Term to 18O Observed Rate Constants. viii Page 51- Evaluation of kg^. I98 5 2 . Rate Data for Acid-Base Catalyzed Hydration of Iso- 200 butyraldéhyde. 55r Correlation of Internal Acid-Catalysis. 226 5^. Major Infrared Bands of the Diamines. 242 55 • Example of Kinetic Run for Hydration of Isobutyral- 245 dehyde. 5 6 . Chemical Shifts of Protonated Trimethylamine. 245 57- Chemical Shifts of Protonated N-Dimethylethylene - 247 diamine. 58 . Data for Run Number 210.805 • 250 59* Data for Run Number 210.664 . 255 6 0 . An Illustration of the Sensitivity of Kq to Change 260 in Percent Transmittance. IX LIST OF FIGURES Page 1. Intramolecular Acid Catalysis. 5 2. Logarithm of the First-Order Rate Constants for the 10 Hydrolysis of Substituted Benzylidene-1,1-dimethyl- ethylamine as a Function of pH. 3. Enzymic Catalysis of Transamination. IT A Plot of the Observed Rates of Hy dr a t ion -Lehydrat i on 50 for Isobutyraldéhyde vs. the Total Buffer Concentration. 5* . A Plot of the General Base Catalyzed Rate Constant for 5^ Dehydration vs. the pKa of the Protonated Catalyst. 6 . Correlation of Chemical Shift "with Percent Unprotonated 62 Methylamine. T • Correlation of Chemical Shift with Percent Unprotonated 64 Trimethylamine. 8 . Correlation of Chemical Shift with Percent Unprotonated 66 Triethylamine. 9- Correlation of Chemical Shift with Percent Unprotonated 68 n-Propylamine. 10. Correlation of Chemical Shift with Percent Unprotonated 70 2-Methoxyethylamine. 11. Correlation of Chemical Shift with Percent Unprotonated 72 ITjN ,N ’ '-Tetramethylethylenediamine. 12. Correlation of Chemical Shift with Percent Unprotonated 74 N ,11 ’ -Tetrame thyl-1,5 -propanediamine. 13. Correlation of Chemical Shift with Percent Unprotonated jS U,H-Dimethylethylenediamine. 14. Evaluation of Equation 42. 77 Page 15. Correlation of Chemical Shift •with Percent Unprotonated 79 1 6 . Evaluation of Equation 4-2. 80 1 7 . Correlation of Chemical Shift with percent Unprotonated 82 U -Dimethyl-1 -hut ane. 1 8 . Evaluation of Equation ^2. 83 19- Correlation of Chemical Shift -with Percent Unprotonated 85 U -Dimethyl-1,5 -pentanediamine. 2 0 . Evaluation of Equation 42. 86 2 1 . Plot of pKa vs. log Kj for Monoamines. 120 2 2 . Plot of pKa vs. log Kq of Monoamines. 121 2 5 . Plot of a* vs. log for Monoamines. 122 2h. Plot of pKa vs. log ko for Monoamines. 127 2 5 . Plot of cr* vs. log ko for Monoamines. 128 2 6 . Plot of pKa vs. log kg for Monoamines. 129 2 7 . Plot of pKa vs. log Kgko for Monoamines. 130 2 8 . A Plot of pH vs. Kjq-^s for MesNCCHs)aNHg- 133 2 9 . A Plot of pH vs. KqoIjs for Mes^CCH2)2KH2 * 136 3 0 . A Plot of pH vs. Kjobs Me2M(CH2)sHH2 . 142 3 1 . A Plot of pH vs. for Me2N(CHg)3l3H2 . 145 3 2 . A Plot of pH vs. for Me2N(CH2)4HH2 . 149 3 3 . A Plot of pH vs. KgQ^g for Me2N(CHg)4HH2 - 152 3^. A Plot of pH vs. KjQijg for Me2N(CH2)5UH2 - 156 3 5 . A Plot of pH vs. KQQi3g for Me2N(CH2)sNH;2 . 159 3 6 . A Plot of pKa vs. log for Diamines. 165 XI Page 5T- Plot of a* vs. log for Diamines. l66 3 8 . Plot of pKa vs. log Kg. I67 3 9 . Plot of a* vs. log Kq for Diamines. 168 40. A Plot of pH vs. ksots Me2ÎT(CH2)2im2 . I82 41. A pH-Rate