Schiff base derivatives of l-methyl(benzyl~-2,5-dimethylpiperidin-4-ones with phenyl, a-pyridyl, benzyl, and 8-hydroxyethyl substituents attached to the imine nitrogen atom react with organometallic compounds to give analogously substituted piperidlne bases with methyl, allyl, phenyl, and benzyl substituents in the 4-position. Pure individual geometric isomers of these newly synthesized compounds have been isolated and their structures determined.
The reaction of Schiff bases with Grignard reagents has been known for more than 70 years [I]. This method has been applied to the synthesis of amines with physiological activities [2]. The most interesting compounds in this regard are azomethines prepared in quantitative yields from y-piperidones.
There have been only limited reports concerning the reactions of these types of derivatives with organometallic compounds [3].
As part of our continuing studies of the synthesis and three dimensional structures of y-aminosubstituted piperidines, we have examined the preparation of potential biologically active y-aminopiperidine derivatives from azome~hines synthesized from 1-methyl(benzyl)-2,5dimethylpiperidin-4-ones with the corresponding aromatic, aliphatic-aromatic, and aliphatic amines, i, 2,5-Trimethyl-4-N-phenyl (a-pyridyl, benzyl, 8-hydroxyethyl) iminopiperidines (I-IV) and l-benzyl-2,5-dimethyl-4-N-phenyliminopiperidine (V) [3, 4] were used as the starting materials for these syntheses. Special attention was paid in this study of their reactions with organometallfc compounds to the possibility of the formation of geometric isomers, since the addition of organometallic compounds to the imine double bond results in the formation of products with three asymmetric centers. In several cases it was possible to determine using PMR spectroscopy the formation of several isomers and to show the structures of these isomers, which were isolated in pure form by chromatography.
Reaction of azomethine I with benzylmagnesium chloride (bromide) gave one of the isomers of i, 2,5-trime thyl-4-benzyl-4-N-phenylaminopiperidine (VI, mp 134-134. SaC).