Nitrogen bridgehead compounds. Part 42. Cyclization of diethyl 2-(2-pyridyl-aminomethylene)-succinates and -glutarates in ethanolic sodium ethoxide

Abstract

2-(Pyridylaminomethylene)-succinates (1) and -glutarates (2) were treated with ethanolic sodium ethoxide solution. The succinates (1) gave, in reversible reactions, pyridopyrimidines (3) and pyridylpyrrolinones (5), and also underwent Z–E geometric isomerization. The cyclizations (Z)-(1) to (3) and (E)-(1) to (5) were more rapid than the isomerization of (1). Thus, short (1-min) reactions starting from (Z)-(1) produced the pyridopyrimidine (3) and those from (E)-(1) the pyridylpyrrolinone (5) in good yield. Longer (15-min) reactions yielded equilibrium mixtures, consisting mainly of pyridylpyrrolinones (5). Substituents at position 6 of the pyridine ring inhibited the formation of the pyridopyrimidines, whereas those at position 3 hindered or inhibited the formation of the pyridylpyrrolinones.

The unsubstituted glutarate (2a) formed the pyridopyrimidine (4a) whereas the 6-substituted ones did not yield any cyclic product.

Results of the sodium ethoxide ring closure were compared with those of the previously studied POCl₃–PPA and thermal cyclizations.