A simple synthesis of (±)-1,2,3,6-tetrahydro-2,3′-bipyridine (anatabine) and (±)-3-(2-piperidinyl)pyridine (anabasine) from lithium aluminum hydride and pyridine

Abstract

The hydrolysis of a pyridine solution of lithium tetrakis(N-dihydropyridyl)aluminate (LDPA), which was prepared at 0 °C, yields a mixture of 1,4-, 1,2-, and 2,5-dihydropyridines (DHPs) in a ratio of 26:37:38. The subsequent reversible base-catalyzed condensation of a 1:1 mixture of 1,2- and 2,5-DHPs carried out in the presence of oxygen affords an 89% yield of (±)-anatabine. When the reaction mixture is allowed to stand in the presence of oxygen, anabasine is slowly formed from anatabine by the reaction of the residual DHPs. Anatabine can also be converted into (±)-anabasine by catalytic hydrogenation. Keywords: lithium aluminum hydride, pyridine, anatabine, anabasine.