Synthesis and binding activity of 4-azanicotine

4-Azanicotine (1) has been synthesized by the cyclopropylimine rearrangement. A study of several Lewis acids as possible catalysts for the NMF-mediated cyclopropyl imine rearrangement of cyclopropyl-2-pyrazinylmethanone (4) indicated that both aluminum chloride and magnesium chloride are suitable catalysts, lithium bromide shows only a trace of activity and zinc chloride, titanium tetrachloride, and titanium tetraisopropoxide show no activity. Compound 1, in which the aromatic ring is less basic than in nicotine, and 6-aminonicotine (5), in which the aromatic ring is more basic, have been compared with the binding properties of nicotine in the P2 rat brain preparation. Compound 1 binds with an affinity very similar to that of nicotine at two of the receptor sites, 5 binds at these sites but with a lower affinity. Unlike nicotine, 1 and 5 do not bind at the very high affinity 'upregulatory' site.