ACETYLENIC DIMERIZATION UNDER BASIC CONDITIONS
Keywords:
Acetylenic dimerization, Aminoactylenic derivative, Azetidine derivative, Aziridine derivative, Mannich reactionAbstract
Objective: The lack of information concerning the pharmacological activity of amino acetylenic amide derivatives in which the cyclic amine is aziridine or azetidine promoted our interest to synthesize N-[4-(1-azeridinyl)-2-butynyl] pyrrolide-1,3-dione 4, N-[4-(1-azetidinyl)-2-butynyl] pyrrolidine-1,3-dione 5 and N-[4-(1-pyrrolidnyl)-2-butynyl]pyrrolide-1,3-dione 6.
Methods: Melting points, IR, 1H-NMR 13CNMRspectra were measured.
Results: Dimerization of 2-(prop-2-yn-1-yl) pyrrolidine-1,3-dione was generated rather than Mannich product, while using pyrrolidine as base in Mannich reaction generated the expected Mannich product. Rationalization for the mechanism of dimerization and Mannich adduct are discussed.
Conclusion: Mannich reaction may afford the dimerization product of the acetylenic compounds rather than Mannich adduct.
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References
Everett GM. Tremor produced by drugs. Nature 1956;177(4522):1238.
Everett GM. Extra pyramidal system and Neuroleptics, Edition Psychiatric, Bordeleau, JM: Montreal; 1961. p. 182.
Baker WW, Hosko MJ, Rutt WJ, McGrat JR. tremorine-induced rang and its antagonism by atropine. Proc Soc Exp Biol Med 1960;104:214-7.
Dahlbom R, Karlen B, George R, Jenden DJ. Synthesis and pharmacology of N-(4-diethylamino-2-butynyl)-succinimide (DKJ 21), a new central anticholinergic agent. Life Sci 1966;5(17):1625-31.
Dahlbom R, Lindeke B, George R, Jenden DJ. Acetylene compounds of potential pharmacological Value. VIII. N-(4-Dialkylamino-2-butynyl)-Substituted cyclic imides. J Med Chem 1966;9(6):843-6.
Karlen B, Lindeke B, Lindgren S, Svensson KG, Dahlbom R, Jenden DJ, et al. Acetylene compounds of potential pharmacological value. XIV. N-(tert-aminoalkynyl)-substituted succinimides and maleimides. Class of central anticholinergic agents. J Med Chem 1970;13(4):651-7.
Lindquist A, Lindgren S, Lindeke B, Karlen B, Dahlbom R, Blair Jr MR. N (perhydro azepinoalkynyl)-and N-(perhydro azocinoalkynyl) succinimides asoxotremorine antagonists. J Pharm Pharmacol 1970;707:22.
Lindquist A, Lindgren S, Lindeke B, Karlen B, Dahlbom R, Blair Jr MR. Acetylene compound of potential pharmacological value. XVI. N-(perhydro azepinoalkynyl)-and N-(perhydro azocinoalkynyl) succinimides. Acta Pharm Suec 1972;9(2):93-8.
Muhi-eldeen Z, Shubber A, Musa N, Muhammed A, Khayat A, Ghantous H. Synthesis and biological evaluation of N-(4-t-amino-2-butynyloxy) and N-(4-t-amino-2-butynyl) phthalimides. Eur J Med Chem 1980;15:85-8.
Muhi-eldeen Z, Cosmo NA, Ghantous H, Khayat A. Synthesis and biological evaluation of N,N’-di-(4-t-amino-2-butynyl0promellitic acid diimides. Eur J Med Chem 1981;16(1):91-3.
Tramotini M. Advances in the chemistry of mannich bases. Synthesis 1973;12:703-75.
Fernandez JE. A study of the intermediates in the Mannich reaction of nitroalkanes. Tetrahedron Lett 1964;5(39):2889-93.
Behr OM, Eglinton G, Galbraith AR, Raphaed RA. Macrocyclic acetylenic compounds. Part II. 1,2:7,8-Dibenzocyclododeca-1,7-diene-3,5,9,11-tetrayne. J Chem Soc 1960;3614-25.
Hay AS. "Oxidative coupling of acetylenes II". J Org Chem 1962;27(9):3320-1.
Sondheimer F, Amiel Y, Wolovsky R. Unsaturated macrocyclic compounds VIII. oxidation of terminal diacetylenes five new macrocyclic rings. J Am Chem Soc 1959;81:4600-6.
Van Roosmalen JH, Jones E, Kevelam HJ. A novel polycyclic triamine derivative of tridehydro[12]annulene and its nitroxides. Tetrahedron Lett 1972;13(19):1865-8.
Sondheimer F, Wolovsky R, Amiel Y. Unsaturated macrocyclic compounds. XXIII. The Synthesis of the Fully Conjugated Macrocyclic Polyenes Cycloöctadecanonaene ([18]Annulene), Cyclotetracosadodecaene (24) Annulene), and Cyclo triacontapentadecaene ([30]Annulene. J Am Chem Soc 1962;84(2):274-84.