The catalytic alpha-methylation of pyridines

Abstract

Heating pyridines with Raney nickel and 1-decanol resulted in methylation at the free alpha positions. [Diagram] Similarly, 3-picoline gave 2,5-lutidine, 4-picoline gave 2,4-lutidine and 2,4,6-collidine, 4-methoxypyridine gave 2-methyl-4-methoxypyridine, quinoline gave 2-methylquinoline and 8-methylquinoline, phenol gave o-cresol, and benzoquinuclidine gave 8-methylbenzoquinuclidine. The specificity of this unusual methylation reaction makes it unique from the normal aromatic substitution reactions of pyridine. The mechanism is postulated to involve dehydroxymethylation of 1-decanol to produce nonane and a one-carbon fragment (believed to be similar to methylene) adsorbed on the catalyst. The specificity of the reaction indicates that pyridine is adsorbed on the catalyst via the nitrogen lone-pair electrons thus making the alpha-carbons available to attack by the one-carbon fragment adsorbed on the Raney nickel. The methylation of phenol and benzoquinuclidine, although in low yield, showed that lone-pair electrons other than those of pyridine can act to anchor a molecule to the catalyst and allow methylation.