ARYLPYRIDINES: PART I. ORIENTATION IN THE REACTION OF PHENYLLITHIUM WITH SOME 3-SUBSTITUTED PYRIDINES

Abstract

The orientation of the entering phenyl substituent in the addition of phenyllithium to 3-picoline and nicotine has been studied. In the first case the main product was 3-methyl-2-phenylpyridine together with a small amount of 5-methyl-2-phenylpyridine; the ratio of the isomers being 19:1. The structure of the isomers was established by oxidation to the corresponding phenylnicotinic acids, by infrared and n.m.r. spectroscopy. Quantitative analysis of the crude mixture of isomers was effected by vapor phase chromatography. Phenylation of nicotine gave 2-phenyl- and 6-phenyl-nicotine in the ratio of 1:1. Separation of the isomers was effected by preparative vapor phase chromatography and their orientation established as above. Evidence that the 3-substituent exerts an appreciable steric effect in the end product of the addition is presented. The results are taken to mean that addition of phenyllithium, and probably of other nucleophilic reagents, to 3-substituted pyridines occurs preferentially at the 2-position but the 3-substituent, if sufficiently bulky, may exert a steric effect resulting in appreciable addition at the 6-position also.