Tetrahydropyridine to Azocine Ring-Expansion Reactions

Significance

A ring-expansion reaction of tetra­hydropyridines to azocines is reported. The precursor tetrahydropyrido[4,3-d]pyrimidines (1), synthesized by condensation of 4-pideridinone-2-carboxylic esters with amidines (A. H. Cook, K. J. Reed J. Chem. Soc. 1945, 399-402), upon Michael addition with acetylene carboxylic esters, lead to intermediate zwitterions B which undergo ring expansion to form pyrimidoazocines under mild conditions in moderate to good yields. The presence of methanol is crucial for the success of the reaction; no product was observed when using MeCN, THF or DMF. Involvement of methanol in the ring-opening process B was proposed. A single-crystal X-ray structure analysis confirmed the structure of one of the pyrimidoazocine derivatives.