IODOMETHYLATION OF NICOTINE - UNUSUAL EXAMPLE OF COMPETITIVE NITROGEN ALKYLATION

Alkylation of nicotine with 1 eq of iodomethane in either methanol or acetonitrile leads to approximately 2.5:1 mixtures of N''-methylnicotinium iodide (4) and N-methylnicotinium iodide, and not to only 4 as previously indicated. The alkylation results reflect kinetic control of product. The products appear to be formed irreversibly under the reaction conditions. Alkylation of the nicotine analogue N,N-dimethyl-3-aminomethylpyridine with 1 eq of iodomethane led only to trimethyl-3-picolylammonium iodide. Competitive alkylation experiments between nicotine and pyridine and N-methylpyrrolidine indicate that alkylation on nicotine''s pyrrolidine N is decelerated, and the causes for this anomalous example of competitive N alkylation are discussed.