Reaction of 4-cyano-1,3-dihydroxy-5,6,7,8-tetrahydroisoquinolines with vilsmeier reagent: structure and mechanism of formation of [2,7]naphthyridines

Abstract

Reaction of 4-cyano-1,3-dihydroxy-5,6-7,8-tetrahydroisoquinoline 1, with Vilsmeier reagent gave the chloro aldehyde 2, dichloro [2,7]naphthyridine, 5 and monochloro [2,7]naphthyridine 8, identified by spectral data [Mass, 1H & 13C NMR, NOE and HETERO COSY]. Structure 5 has been confirmed by X-ray crystal structure analysis. Reaction of 1a–f, similarly, gave the corresponding compounds 2a–f, 5a–f and 8a–f. The starting tetrahydroisoquinolines, 1a–f were synthesised by the reaction of the corresponding β-keto esters with cyanoacetamide. Reaction of 8 with POCl 3 gave in almost quantitative yield, the dichloro compound 5. An acceptable mechanism has been proposed for the formation of the products.