Nucleophilic addition versus metalation of 4- and 2-methylpyridine studied by multinuclear magnetic resonance spectroscopy

Abstract

Interaction of 4-methylpyridine with n-butyl-lithium in THF affords a 67:33 mixture of the 1,2-nucleo-philic addition product and the laterally metalated derivative of the heterocycle, respectively, as shown by ¹³C and ¹⁵N n.m.r. spectroscopy. While mixtures were also obtained from 4-methylpyridine and methyl- or t-butyl-lithium. only metalation was realized with the lithium salts of di-isopropylamine and 2,2,6,6- tetramethylpiperidine. A regular trend was noted with other 4-alkylpyridines and n-butyl-lithium culminating in exclusive 1,2-addition on 4-n-butylpyridine. The ¹³C n.m.r. spectrum from 2-methyl-pyridine and n-butyl-lithium also showed the presence of both addition and metalation derivatives; however, the former material was present only to the extent of 3%.