Intramolecular cyclization of N-aryl-3-phenylprop-2-ynamides

Abstract

Heterocyclic quinoline system constitutes the basic structural fragment of many natural and synthetic biologically active substances [1–3]. Therefore, development of new methods for the preparation of quinoline derivatives is an important problem of organic chemistry. A promising procedure for the synthesis of 4-arylquinolin-2(1H)-ones is based on intramolecular cyclization of N,3-diarylprop-2-ynamides by the action of acid reagents. Iwai and Hiraoka [4] were the first to obtain in such a way 4-phenylquinolin-2(1H)-one (IIa) in 81% yield; it was synthesized by heating N,3-diphenylprop-2-ynamide (Ia) in polyphosphoric acid at 120°C (reaction time 0.5 h) [4]. The transformation of amide Ia into quinolinone IIa was also promoted by other reagents, such as solid superacids H-USY and Nafion SAC-13 [5], Lewis acid AlCl3 [6], and superacid CF3SO3H [5, 6]. In continuation of our preceding studies on intramolecular reactions of vinyl type cations in various superacidic systems [7], we specially examined the transformation of N-aryl-3-phenylprop-2-ynamides Ia– Ic into 4-phenylquinolin-2(1H)-ones IIa–IIc [8]. Protonation of the triple C≡C bond in Ia–Ic with trifluoromethanesulfonic acid yields vinyl cations A which undergo cyclization to final products IIa–IIc. According to the data of [5, 6], N-phenyl amide Ia in CF3SO3H at 25°C in 100 h is converted into quinolinone IIa as the only product (yield 97%). We found that the transformation of Ia in CF3SO3H at a higher temperature (50°C, reaction time 2 h) leads to a mixture of two products, quinolinone IIa and vinyl trifluoromethanesulfonate Z-III (yield 52 and 30%, respectively). Compound III was assigned Z configuration of the double C=C bond, taking into account that analogous vinyl trifluoromethanesulfonates derived from 3-arylprop-2-ynoates in CF3SO3H at elevated temperature also have the structure of Z isomers [9, 10]. Presumably, the formation of Z-III via reaction of intermediate cation A with trifluoromethanesulfonic acid molecule is characterized by a higher activation barrier than alternative intramolecular cyclization of A to quinolinone IIa. Provided that the process is controlled thermodynamically (CF3SO3H, 20°C, 30 days), amide Ia is converted into compound IIa as the only product (yield 88%). Under analogous conditions, N-(3-meth-