Zur Bildung von Pyridinen aus 1,5‐Diketonen

Abstract

Pyridinabkommlinge, die in 2,QStellung substituiert sind, sind nicht ohne pharmakololgisches Intereslse, wofiir die Lobeliaalkaloide, deren eines, das Lobelin, von groi3er praktischer Bedeutung ist, als Beispiel dienen miigen. W i e 1 a n d und D r i s h a u s I) gingen zur Synthese dieser Alkaloide von dem Tetraketon 1,7-Dibenzoylheptadion-2,6 aus, H~C~.CO.CH,. CO CO. C H~. ~0 . c~~~ das sowohl als zweifaches 1,3-Diketon wie auch als 1,5-Diketon auf-gefai3t werden kann. Dieses Ausgangsmaterial weist naturgemaii3 durch das Vorhandensein von vier Ketogruppen, die zweimal durch je eine, einmal durch drei Methylengruppen getrennt sind, besondere Eigenschaften hinsichtlich der Enolisierung auf.

Chemistry of dihydropyridines

“…Some 1,5-diketones were said to give dihydropyridines with ammonia while others did not. 385,387,393 This confusion was cleared up only recently when it was shown394 that many so-called 1,5-diketones were in fact 3-hydroxycyclohexanones, i.e., products of a subsequent intramolecular aldol condensation. The action of ammonia on the diketone 86 gave the isolable intermediate 87 which cyclized with concomitant dehydrogenation to 2,4,6-triphenylpyridine rather than to the expected dihydropyridine.…”

“…The use of primary amines instead of ammonia in the Hantzsch synthesis is rare;338 yields are reported to be low47 or the reaction fails completely.62, 429 Better results are obtained by first forming the substituted enamines RNHCH=CHX, where X = C02Et,430-433 CN,363 or COMe.86,366,366 Benzalaniline, which supplied both benzaldehyde and aniline, gave a dihydropyridine with ethyl acetoacetate.329,431 1,5-Diketones are cyclized by primary amines,239 '387,392,411,433 including hydrazine. 386,387 The action of hydroxy lamine on 1,5-diketones affords pyridines (ref 8, p 307).…”