Organometallic Methylation of Nicotine and Nicotine N-Oxide. Rection Pathways and Racemization Mechanisms

Article abstract of DOI:10.1021/jo00173a023

The reaction of nicotine with methyllithium leads to 2-methylnicotine as a major product in addition to the previously reported 4- and 6-methylnicotines.The reaction of nicotine N-oxide with methylmagnesium bromide furnishes both 2- and 6-methylnicotine.The product composition of these reactions is strongly dependent on the experimental conditions; the effects of solvent, temperature, and relative reagent concentration are presented.The methyllithium reactions lead to partially racemized methylnicotines, and the recovered nicotine is often nearly optically pure.Independently, (S)-(-)-6-methylnicotine was treated with methyllithium and was recovered with complete retention of optical activity.These results suggest that loss of optical purity in the formation of methylnicotines in these methyllithium reactions occurs during the reaction itself and is not due either to racemization of the starting material or to subsequent racemization of the initially formed product.