Cascade synthesis of 2-amino-5-(4-methoxyphenyl)-4-phenyl-1,3-thiazole by reaction of 4-chloro-N-[2,2-dichloro-1-(4-methoxyphenyl)-2-phenylethyl]benzenesulfonamide with thiourea

Abstract

4-Chloro-N-[2,2-dichloro-1-(4-methoxyphenyl)-2-phenylethyl]benzenesulfonamide reacted with thiourea on heating in DMF in the presence of sodium carbonate to give 5-(4-methoxyphenyl)-4-phenyl-1,3-thiazole-2-amine. A probable reaction scheme includes cyclization of the initial N-dichloroethyl amide to N-sulfonyl-2,3-diaryl-2-chloroaziridine which undergoes isomerization with opening of the three-membered ring to 1-arylsulfonylamino-2-chloro-2-(4-methoxyphenyl)-1-phenylethene. The subsequent heterocyclization in the reaction with thiourea is accompanied by aromatization via elimination of the arenesulfonamide fragment. Ar = 4-MeC 6 H 4 (a), 4-MeOC 6 H 4 (b).We previously developed convenient methods for C-amidoalkylation of aromatic, functionally substituted aromatic, and heteroaromatic compounds with the use of polychloroacetaldehyde imines as amidoalkylating agents [1-3]. As a result, a wide series of N-polychloroethylsulfonamides RSO 2 NHCH(Ar)CCl 2 X became accessible, and we were able to initiate studies on their biological activity and chemical reactivity. Synthetic importance of N-polychloroethylsulfonamides is determined by the presence in their molecules of NH group and polyhalomethyl fragment; it was demonstrated by the preparation on their base of biologically active N-protected amino acids [4], as well as by cascade reactions leading to amidines [5], aminocarbonyl compounds [6], imides [7], macroheterocyclic systems [8], and aziridines [9]. In addition, it was found that reactions of N-(1-aryl-2,2,2-trichloroethyl)arenesulfonamides with thioamides in dimethylformamide in the presence of inorganic bases lead to the formation of substituted 1,3-thiazoles [10]. Scheme 1.

One-pot regioselective synthesis of new 5-(arylsulfonylamino)imidazo[2,1-b]thiazoles

“…Anisole derivatives 2a and 3a were previously prepared according to this protocol. 30 The corresponding thioanisole derivatives 2b and 3b were synthesized during the present work and have not been previously described.…”