The chemistry of some dihydropyridine derivatives

Abstract

Reactions of 4-chloromethyl-1,4-dihydropyridine and 4-(l-chloroethyl)-1,4-dihydropyridine derivatives with enolate ions from 3-dicarbonyl compounds have been studied, and shown to give the corresponding 4-substituted-4,5-dihydroazepines under mild conditions. Under vigorous conditions intramolecular Michael addition takes place (provided the dicarbonyl substituent possesses an acidic hydrogen atom) giving 2-azabicyclo-(3.2.1)oct-3-enes; the stereochemistry of this reaction is considered. The reactions of some simpler nucleophiles with these chloro-compounds were also investigated. -- Rearrangements of 4-cyano-4,5-dihydroazepines in both acidic and basic conditions were reinvestigated. The isolation of a ring-opened intermediate and a substituted dihydro-2-pyridone from the acid-catalysed rearrangement provide support for a postulated mechanism. -- The competitive reactions of chloroalkyl and bromoalkyl substituted 1,4-dihydropyridines with different bases were studied in both concentrated and dilute solution and a mechanism for the ring expansion reaction was postulated. -- Methyl 5-acetyl-2,6-dimethylnicotinate and its dihydro-compound were synthesized, particularly for mass spectral correlations. Mass spectra of some 1,4-dihydropyridines,4H-azepines,4,5-dihydroazepines, 2-azabicyclo(3.2.1)oct-3-enes, furo(2,3-b)pyridines, pyrrolo(2,3-b)pyridines,and β-(3-methoxycarbonyl-2-methyl-l-pyrrolyl)-crotonic acid are reported and discussed.