Studies on the Fischer indole synthesis: rearrangements of five-, six- and seven-membered cyclic hydrazones of pyrazoline, tetrahydropyridazine and tetrahydro-1,2-diazepine series in polyphosphoric acid

Abstract

The rearrangements of a few cyclic phenylhydrazones structurally related to 1-phenyl-Δ²-pyrazoline, 1-phenyl-1,4,5,6-tetra hydropyridazine, and 1-phenyl-4,5,6,7-tetrahydro-1,2-diazepine in hot polyphosphoric acid (PPA) are described. The five-membered-ring substrates (the pyrazolines) did not undergo the [3,3] sigmatropic rearrangement typical of the Fischer indolization, the main reaction course being homolytic N–N bond cleavage, leading to benzidine and its 4-(2-benzoylethyl)-4′-(3-phenyl-Δ²-pyrazolin-1-yl) derivative. The six-membered heterocycles underwent two different reactions, both evolving the tautomeric enehydrazine form: the first one is the [3,3] sigmatropic rearrangement, expected for open-chain hydrazones, affording 4-acyl-1,2,3,4-tetrahydroquinoline derivatives; the second one is a retro-Diels–Alder reaction producing methyleneaniline and α,β-unsaturated carbonyl, compounds. The seven -membered -ring substrate gave a 5-acyltetrahydrobenz[b]azepine, resulting from the [3,3] rearrangement, together with both a pyrrolidine and a pyrazine by-product; their formation involves homolytic N–N bond cleavage of the ring, a δ hydrogen abstraction, followed by intramolecular or intermolecular ring closure. Chemical proofs are given for the new structures.