4-METHOXY-1-METHYLPYRIDINIUM IODIDE . GRIGNARD PRODUCTS AND TRANSFORMATIONS THEREOF

Reaction of 4-methoxy-1-methylpyridinium iodide (1) with benzyl- or p-methoxybenzylmagnesium chloride, followed by borohydride reduction, has produced (depending upon solvent media) 2-benzyl-1-methyl derivatives of 4-methoxy-1,2,3,6-tetrahydropyridine (4a,b) or 4,4-dimethoxypiperidine (5a,b), apparently through the 2-benzyl-4-methoxy-1-methyl-1,2-dihydropyridines (2a,b). Treatment of 2a,b with methanol-aqueous sodium hydroxide gave 4(1H)-pyridones, 6a,b. Direct quenching of the Grignard mixture from 1 and benzylmagnesium chloride with ammonium chloride-ammonium hydroxide yielded, instead of 2a, 4-amino-2-benzyl-2,3-dihydro-1-methylpyridinium iodide (3), readily converted into 6a or the 4-aminopiperidine (7). Acid treatment of 4 or 5 afforded 4-piperidones (8) and reduction of 6 led to diastereoisomeric 4-piperidinols (9) which were also obtained in low yield, directly from 2. Piperidinol 9b was also obtained from 8b. Known benzomorphans 10a,c resulted from cyclodehydration of 9a,b. The mechanism for the formation of the anomalous (when compared with the 4-alkyl series) products is discussed. © 1969, American Chemical Society. All rights reserved.