Part I: Reactions of Nucleophiles with Pyridinium Ions Cyanide Ion Reactions with Some Pyridinium Ions Part Ii: Sodium Borohydri

University of New Hampshire University of New Hampshire Scholars' Repository Doctoral Dissertations Student Scholarship Spring 1966 PART I: REACTIONS OF NUCLEOPHILES WITH PYRIDINIUM IONS CYANIDE ION REACTIONS WITH SOME PYRIDINIUM IONS PART II: SODIUM BOROHYDRIDE REDUCTION OF THE METHYL IODIDE SALTS OF FORMYL AND BENZOYLPYRIDINE OXIMESAND OXIME, METHYL ETHERS GEORGE JAMES GAUTHIER Follow this and additional works at: https://scholars.unh.edu/dissertation Recommended Citation GAUTHIER, GEORGE JAMES, "PART I: REACTIONS OF NUCLEOPHILES WITH PYRIDINIUM IONS CYANIDE ION REACTIONS WITH SOME PYRIDINIUM IONS PART II: SODIUM BOROHYDRIDE REDUCTION OF THE METHYL IODIDE SALTS OF FORMYL AND BENZOYLPYRIDINE OXIMESAND OXIME, METHYL ETHERS" (1966). Doctoral Dissertations. 828. https://scholars.unh.edu/dissertation/828 This Dissertation is brought to you for free and open access by the Student Scholarship at University of New Hampshire Scholars' Repository. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of University of New Hampshire Scholars' Repository. For more information, please contact [email protected]. This dissertation has been microiihned exactly as received 67-157 GAUTHIER, George James, 1940- PART I; REACTIONS OF NUCLEOPHILES WITH PYRI- DINIUM IONS. CYANIDE ION REACTIONS WITH SOME PYRIDINIUM IONS. PART H: SODIUM BOROHYDRIDE REDUCTION OF THE ME T H Y L IODIDE SALTS OF FORMYL- AND BENZOYLPYRIDINE OXIMES AND OXIME, METHYL ETHERS. University of New Hampshire, Ph.D., 1966 ^ Chemistry, organic i University Microfilms, Inc., Ann Arbor, Michigan Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. PART I REACTIONS OF NUCLEOPHILES WITH PYRIDINIUM IONS. CYANIDE ION REACTIONS WITH SOME PYRIDINIUM IONS. PART II SODIUM BOROHYDRIDE REDUCTION OF THE METHYL IODIDE SALTS OF FORMYL- AND BENZOYLPYRIDINE OXIMES AND OXIME, METHYL ETHERS. BY GEORGE JAMES GAUTHIER A THESIS Submitted to the University of New Hampshire In Partial Fulfillment of The Requirements for the Degree of Doctor of Philosophy Graduate School Department of Chemistry May, 1966 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. This thesis has been examined and approved. QoyuJy C?. C j . ^ , J^l/musTf^ k!. Gb^olofi. 1 3 j Date Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGEMENTS The author wishes to express his thanks to the Chairman and faculty of the Department of Chemistry for their instruction and assistance during the past four years. Mrs. Pearl Libby is thanked for the typing of this thesis and for her numerous kindnesses. Mrs. Sharon Bryant is also thanked for assisting in the typing of this thesis. The author is especially indebted to Dr. Robert E. Lyle, under whose guidance this research was conducted, for the many fruitful discussions and numerous personal con siderations which have made these four years of work enjoy able as well as instructional. The author is indebted to the National Cancer Insti tute for a research grant for the period 1962-1964, and to the National Institutes of Health for a research fellowship for the period 1965-1966. Finally, the author wishes to express his deepest gratitude to his parents and wife whose years of understand ing, sacrifice, and encouragement have made the completion of this work possible. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS Page LIST OF TABLES............................... LIST OF ILLUSTRATIONS IX PART I - CYANIDE ION REACTIONS WITH SOME PYRIDINIUM IONS. I. INTRODUCTION................................. 1 II. DISCUSSION AND RESULTS...................... 1. Preparation of Pyridines and Pyridinium Salts..................................... 11 2. Spectroscopic Properties of Pyridinium Salts..................................... 13 3. Preparation and Properties of 4-Cyano- 1.4-dihydropyridine s .................... 16 4. Studies of the Reaction of Sodium Cyanide with Pyridinium Salts in Methanol by Ultraviolet absorption Spectroscopy............................. 22 a) 3-Ethoxycarbonyl-5-bromopyridinium Salt................................. 24 b) 3-Benzoylpyridlnium Salts........... 28 c) 3-Acetylpyridinium Salts............ 30 d) 3-Cyanopyridinium Salts.............. 32 e) 3-Cyano-5-methylpyridinium Salts.... 33 f) 3-Carbamoylpyridinium Salts......... 35 g) Reactions of Other Quaternary Salts with Sodium Cyanide................. 37 5. The Isolation and Characterization of the Intermediate 6-Cyano-l,6-dihydropyridine................................. 40 6 . Studies of the Isomerization of 6-Cyano-l,6-dihydropyridines to 4-Cyano- 1.4-dihydropyridines Using NMR Spectro scopy..................................... 41 7. Summary................................... 50 IV Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. III. EXPERIMENTAL................................ 1. General.................................. 52 2. Methods of Preparation of Quaternary Salts................................... 54 3. Preparation of 3,5-Symmetrically Disubstituted Pyridines................ 59 4. Preparation of 4-Cyano-1,4-dihydropyridines............................... 69 5. Studies of Cyanide Addition Reactions Using Ultraviolet and Visible Absorption Spectroscopy.................... ....... 85 6 . Studies of Cyanide Addition Reactions Using Nuclear Magnetic Resonance Spectroscopy............................ 93 7. Preparation of 1-Methyl-3-ethoxycarbonyl-4-cyano-5-bromo-1,4-dihydro pyridine................................ 95 8 . Preparation of l-Methyl-3-ethoxycarbonyl- 5-bromo-6-cyano-l,6“dihydropyridine.... 95 9. The Isomerization of l-Methyl-3-ethoxycarbonyl-5-bromo-6-cyano-l,6-dihydropyridine................................ 98 10. Rate of Isomerization of l-Methyl-3- ethoxycarbonyl-5-b romo-6-cyano-1,6- dihydropyridine as a Function of Cyanide Ion Concentration.............. 101 11. Studies of the Isomerization of 1- Methyl-3-ethoxycarbonyl-5-bromo-6- cyano-l,6-dihydropyridine as a Function of Solvent.................... 103 'j. PART II.- SODIUM BOROHYDRIDE REDUCTIONS OF PYRIDINIUM SALTS I. INTRODUCTION................................. 105 II. DISCUSSION AND RESULTS...................... 1. Preparation of Pyridine Oximes and Oxime, Methyl Ethers, and Their Methyl Iodide Salts............................ 109 2. Solvent Dependence of the Ultraviolet Absorption Spectra of Pyridinium Oxiirtes and Oxime, Methyl Ethers....... 109 V Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 3. Sodium Dithionite Reduction of Pyridinium Salts........................ 112 4. Sodium Borohydride Reductions of Pyridinium Salts........................ 114 5. Preparation of l-Methyl-3-ethoxycarbonyl-5-bromo-1 ,2-dihydropyridine... 115 6 . Diels-Alder Reaction of l-Methyl-4- styryl-1 ,2 ,5,6-tetrahydropyridine with N-Phenylmaleimide................. 116 III. EXPERIMENTAL................................ 1. Preparation of the Quaternary Salts of the Oximes and Oxime, Methyl Ethers of 2-, 3-, and 4-Formyl- and Benzoylpyridines................... [ 118 2. Preparation of 1,4-Dihydropyridines by the Reduction of Pyridinium Salts with Sodium Dithionite................. 129 3. Preparation of Tetrahydropyridines by the Reduction of Pyridinium Salts with Sodium Borohydride................ 132 4. Diels-Alder Reaction of l-Methyl-4- styryl-1 ,2 ,5,6-tetrahydropyridine with N-Phenylmaleimide................. 135 5. Preparation of l-Methyl-3-ethoxycarbonyl-5-bromo-l,2-dihydropyridine... 142 BIBLIOGRAPHY................................ 143 BIOGRAPHICAL DATA........................... 149 VI Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OF TABLES Page PART I - CYANIDE ION REACTIONS WITH SOME PYRIDINIUM IONS. Number I. Properties of 3-Substituted Pyridinium Salts...................................... 55 II. Other Quaternary Salts for Cyanide Addition Reactions........................ 63 III. Ultraviolet Absorption Spectra of Quaternary Salts.......................... 66 IV. NMR Spectra of Pyridinium Salts......... 67 V. Properties of 4-Cyano-1,4-dihydropyridines................................. 70 VI. Ultraviolet Absorption Spectra of 4- Cyano-1,4-dihydropyridines............... 75 VII. NMR Spectra of 4-Cyano-l,4-dihydropyridines................................. 77 VIII. Infrared Absorption Bands of 4-Cyano- 1,4-dihydropyridines..................... 79 IX. Studies of Cyanide Addition to Pyridinium Salts in Methanol............. 86 X. Pyridinium Salts Which Did Not React with Cyanide Ions......................... 90 XI. Studies of Cyanide Addition to Quinolinium Salts in Methanol............ 92 XII. NMR Spectra of 6-Cyano-l,6-dihydro pyridines ................................. 94 XIII. Infrared Spectra of 1-Methyl-3-ethoxycarbonyl-4-cyano-5-bromo-1,4-dihydro pyridine and l-Methyl-3-ethoxycarbonyl- 5-bromo-6-cyano-l,6-dihydropyridine..... 96 XIV. Ultraviolet Absorption Spectra of the Reaction of Sodium Cyanide and Potassium Cyanide with l-Methyl-3-ethoxycarbonyl-5- bromopyridinium Iodide 100 vxi Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. XV. Rate of Isomerization of l-Methyl-3- e th oxyc a rb ony1-5-bromo-6-cyano- 1,6-dihydropyridine as a

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