Louisiana State University LSU Digital Commons LSU Historical Dissertations and Theses Graduate School 1983 The yS ntheses of the Crown Ethers Possessing 2,6-Pyridino Moieties. Hyo Won Lee Louisiana State University and Agricultural & Mechanical College Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_disstheses Recommended Citation Lee, Hyo Won, "The yS ntheses of the Crown Ethers Possessing 2,6-Pyridino Moieties." (1983). LSU Historical Dissertations and Theses. 3894. https://digitalcommons.lsu.edu/gradschool_disstheses/3894 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Historical Dissertations and Theses by an authorized administrator of LSU Digital Commons. For more information, please contact [email protected]. INFORMATION TO USERS This reproduction was made from a copy of a document sent to us for microfilming. 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Zeeb Road Ann Arbor, Ml 48106 8400126 Lee, Hyo Won THE SYNTHESES OF THE CROWN ETHERS POSSESSING 2,6-PYRIDINO MOIETIES The Louisiana State University and Agricultural and Mechanical Ph.D. Col. 1983 University Microfilms International300 N. Zeeb Road, Ann Arbor, Ml 48106 THE SYNTHESES OF THE CROWN ETHERS POSSESSING 2,6-PYRIDINO MOIETIES A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in The Department of Chemistry by Hyo Won Lee B.S., Seoul National University, 1973 M.S., Seoul National University, 1975 August 1983 To my parents and to Ihl Young and Ji-Eun ii ACKNOWLEDGMENT The author would like to express his sincere appreciation to his major professor, George R. Newkome, for his enthusiastic and heuristic guidance throughout the research. Appreciation is also expressed to the members of his research group, especially David W. Evans and Gregory R. Baker, who helped in the writing of the introduction part of this dissertation in order to survive the homestretch. Special thanks are given to his family for spiritual support, without which this work would otherwise be impossible. Also, thanks are given to Dr. Frank R. Fronczek for - ■* X-ray crystallographic analyses and helpful discussions. Lastly, the financial support received from the Coates Memorial Foundation is gratefully acknowledged. iii TABLE OF CONTENTS Pag ACKNOWLEDGMENT ............................................. ii LIST OF TABLES ................... xi LIST OF FIGURES.............................................. xi LIST OF SCHEMES.............................................xii ABSTRACT .......... XV I. INTRODUCTION ........................................1 1-1. Nomenclature................................... 3 1-2. General Synthetic Approaches.............. 6 II. Pyridino Crown Ether .......... 8 II-1. Syntheses of Type 1 Pyridino Crown Ethers ..................................8 (A) General Examples ........................ 8 (B) Pyridinopolyether-Dilactones ........15 (C) 1,4-Dihydro-2,6-Pyridino Crown Ethers.............................18 (D) Nicotinic Crown Ethers ............... 19 (E) Chiral Crown Compounds ............... 20 (F) Multiloop Crowns........................ 26 II-2. Host-Guest Complexation of Type 1 Crown Ethers ................................ 27 (A) Protonated Pyridino Crown Ethers...27 (B) Alkylammonium Salt Complexes ....... 29 (C) Intramolecular Complexes .............34 (D) Diazonium Complexes ...................35 Page (E) Metal Ion Complexation....................37 (F) Complexation of Neutral Guests......... 40 III. Type 2 Pyridino Crown Ether ......... ..........43 III-1. Nicotinic Acid Crown Ethers..................45 III-2. Spiro and Ketonic Crowns ......... 47 IV. Di & Tripyridino Crown Ethers ...................49 IV-1. Type 1 Dipyridino Crown Ethers ............ 49 IV-2. Type 2 Di & Tripyridino Crown Ethers .....52 V. Syntheses of Oligopyridines ......................56 V-1. Syntheses of Oligopyridines from Open-Chain Molecules ................. 56 (A) Cyclization OF Five-Carbon C h a i n ......57 (B) 3-2 Condensation .......................... 58 (C) 2-1-2 Condensation .....................63 VI. E X PERIMENTAL...... 65 1. General Comments............................... 65 2. Ethyl 2 ,6-Dichloronicotinate................ 67 3. 2,6-Dichloro-3-hydroxymethylpyridine...... 67 4. Tetrahydropyranoxymethyl-2,6-dichloro- pyridine...........................................68 5. 3- [ [(Tetrahydropyran-2-yl)oxy]methyl] - 2 ,6 -diethoxypyridine........................... 69 6 . 19-1[(Tetrahydropyran-2-yl)oxy]methyl] - 17<0£ ( 2,6 -pyridino) -2 5 ~coronand-5 > ..........70 v Page 7. Attempted Hydrolysis of 103 and 104. Ether formation..................................71 8 . Hydrolysis of 103 and 104. Preparation of alcohol 105d and 106d.......73 9„ 19-Hydroxymethyl-17<06(2,6 -pyridino)- 2 5~coronand-7 > (105d ).......................... 74 10. 2 ,6-Diethoxy-3-hydroxymethylpyridine (106d)............................................. 74 11. Preparation of Active Manganese Dioxide...74 12. Preparation of Cr0 3 « 2pyridine................ 74 13. 2 ,6-Dichloropyridine-3-carboxaldehyde. Method A ...........................................75 Method B ...........................................75 Method C ...........................................76 14. 2 ,6-Dichloro-3-(diethoxymethyl)pyridine...76 15. 1 9-Formyl-1 7 <O6 (2 ,6 -pyridino)-2 5 *0 2 - coronand-7> (109)............................... 77 16. 2-[2-(6-Mehtylpyridyl)]-1f3-dithiane........78 17. Bis-dithiane.......................... 78 18. 1, 5-Bis[dimethoxy-2-(6 -pyridyl)]pentane...79 19. Diketone 114. Hydrolysis of the Bis-dithiane (112).............................. 80 20. 6 ,6"-Dimethyl-2, 2':6 ',2"-tripyridine........81 2 1 . Ketalization of diketone (114)............... 82 vi Page 22. Bis-ketal di N-Oxide (117)................... 83 23. Bis-ketal dimethanol (119)................... 83 24. Preparation of 2,6-Bis(chloromethyl)- pyridine......................................... 85 A. Dimethyl 2 ,6-pyridinecarboxylate.......85 B. 2 ,6 -Bis(hydroxymethyl )pyridine......... 85 C. 2 ,6-Bis (chloromethyl )pyridine...........86 25. Diethylene Glycol Ditosylate (125)......... 86 26. 2 0 <C>2 ( 2 ,6 -pyridino) 3 - 1 3 * 5 • 1- coronand-5>14,18-dione bis-ethylene glycol ketal (126).............................87 27. 2 0 <O2 (2,6 -pyridino)3 - 1 3 *5*1- coronand-5> 14 ,16-dione (127)................88 28 . 1 8 <0 2 (2 ,6 -pyridino)4 - 1 3 * O2 ♦1“ coronand-6 > (128)..............................89 29. 20<0 3 (2,6 -pyridino)3 - 2 3 *1*5*1— coronand-5>14,18-dione bis-ethylene glycol ketal (129).............................90 30 . 20<0 3 (2,6 -pyridino)2 ~22 *1*5*1- coronand-5> 14,18-dione (130)................91 31 . 1 8 <0 3 (2 ,6 -pyridino)3 -2 2 *1 *0 2 *1“ coronand-6 > (131)..............................92 32. 23<C>2 ( 2 ,6 -pyridino) 4 -1 *0 *1 2 *5 *1- coronand-6>17,18-dione bis-ethylene glycol ketal (132).............................93 vii Page 33. 23<0 2 (2,6 -pyridino)4 -1•0 »12 •5- coronand-6 > 17 ,18-dione (133)................. 94 34. 21<0 2 (2,6 -pyridino)5- 1 •O 2 •12* 0_ coronand-7> (134)............................... 95 35. A. 6-Bromo-2-picoline (136)...................96 B. 6,6'-Dimethyl-2,2'-dipyridine (137)....96 36. 6,6'-Dimethyl-2,2'-dipyridine (137)......... 97 37. A. 6 ,6 '-Dimethyl-2,2'-pyridine Di-N-oxide (140)..................... 97 B. 6 ,6 1-Bis(acetoxymethyl)-2 ,21- pyridine (141)............................... 98 C. 6 .6 1-Bis(hydroxymethyl)-2 ,21- dipyridine (142).............................99 38.