Varenichenko S. Rearrangements of azines and oxazines under Vilsmeier-Haack reagent

It was shown that electrophilic rearrangement of derivatives of 5,6,7,8-tetrahyrdo-1H-spiro[cyclohexane-1,2-quinazolin]-4(3H)-one under Vilsmeier-Haack conditions take place by analogy with earlier described reaction and in the absence of conjugation between the amine and carboxamide groups but with moderate heating. Treatment of 4-methyl-1,5-diazaspiro[5.5]-undec-3-en-2-one with excess of Vilsmeier-Haack reagent was accompanied at the formation of 2-methyl-5,6,7,8-tetrahydroquinoline-3-carboxamide and 2-methyl-N-formyl-5,6,7,8-tetrahydroquinoline-3-carboxamide as a result electrophilic attack of enamine. Formylation of spiro[1,3-benzoxazine-1,2-cyclohexane]-4(3H)-one leading to the extensive rearrangement of the carbon skeleton that makes it possible to arrive at N-(5-formyl-2,3,4,4a,6,7,8,9a-octahydro-1H-xanthen-9-il)-N,N-dimethylimidoformamide's derivative that was shown. Rearrangement of spiro[3,1-benzoxazine-1,2-cyclohexane]-4(3H)-one derivatives under Vilsmeier-Haack conditions from hydroacridine and hydroacridone derivatives markedly developed methods for preparing precursors of reversible acetylcholinesterase inhibitors. In contrast to benzoanalog, hexahydro-4H-1,3-benzoxazin-4-one failed to give xanthene derivatives. Only formylation product (the enamine) was isolated in the reaction of hexahydro-4H-1,3-benzoxazin-4-one with the Vilsmeier-Haack reagent at room temperature. It was proposed rearrangements of azine and oxazine based pyrimidine-to-pyridine or oxazine-to-pyran transformations induced electrophile attack described as AERORC-process.