Efficient Synthesis of 2-Unsubstituted1,3-Selenazoles

Abstract

Two new and efficient methods for the synthesis of 2- unsubstituted 1,3-selenazole , the fragmentation of 2-benzoyl-l,3- selenazole and the cyclization of c-bromoketones with seleno- formamide, are reported. 1,3-Selenazoles are of considerable pharmacological rele- vance. The synthesis of 2-unsubstituted 1,3-selenazoles has been a long-standing problem and only relatively few derivatives have been prepared to date. Haginiwa et a1. have obtained 4-methylselenazole by reaction of HCN, H2Se and chloroacetone, however, in only 3% yield. Recently, Sonoda et a1. have reported the synthesis of 2- unsubstituted 1,3-selenazoles by reaction of ethyl iso- cyanoacetate with isoselenocyanates.5 However, this method is limited to the synthesis of 4,5-disubstituted de- rivatives. In addition, only arylamino-substituted selen- azoles could be prepared, due to the nature of the starting materials employed. Herein, we wish to report a new and convenient method for the synthesi of 2-unsubstituted 1,3-selenazoles which relies on the fragmentation of novel 2-benzoyl-l,3-selenazoles.6 In addition, a second ap- proach to 2-unsubstituted 1,3-selenazoles by cyclization of selenoformamide with u-bromoketones is reported. The cyclization of a-bromoacetophenone (la) with sele- nophenylacetic amide (2a), prepared from phenylacetoni- trile and P2Ses,3b afforded 2-benzyl-4-phenyl-l,3- selenazole (3a) in 99% yield (Scheme 1).7 The oxidation of 3a with K2Cr207 in glacial acetic acid gave 2-benzoyl- 4-phenyl-l,3-selenazole (4a). The yield could be im- proved by the use of Se02 in 1,4-dioxane.8 After several trial experimentations we have found that treatment of an EtOH solution of 4a with NaOH (reflux) afforded the de- sired 2-unsubstituted 1,3-selenazole 5a in 84% yield (58% overall yield from 1a). In addition, sodium benzoate was formed which was isolated in the form of benzoic acid. During the optimization of the fragmentation reaction, the base, solvent, concentration and reaction time proved im- portant parameters.?