Concise Synthesis and Displacement Reactions of Model 3-(Alkylthio)- 6-chloro- and 2,6-Dichlorothieno[2,3-e][1,4,2]dithiazine 1,1-Dioxides

Abstract

A series of 3-(alkylthio)-6-chlorothieno[2,3-e][1,4,2]dithiazine 1,1-dioxides (7a - e) were prepared via interaction of deprotonated 2,5-dichlorothiophene-3-sulfonamide with carbon disulfide under reflux, followed by alkylation with alkyl halides. Employment of dimethyl sulfate afforded the isomeric 2-methyl-3-thione derivative 8 together with the expected 3-(methylthio) derivative 7a in a molar ratio of 1 : 4. Treatment of 7a or 10 with ethylamine, aniline or p-chloroaniline produced the corresponding N-ethyl- (or N-phenyl)-6-chlorothieno[2,3-e][1,4,2]dithiazine-3-amine 1,1-dioxides 3a - c. Likewise, interaction of 7a with methylhydrazine (or phenylhydrazine) gave the respective 3-(1-methylhydrazinyl or 2-phenylhydrazinyl) 1,1-dioxides 9a, b. Desulfonation of 6-chloro-3-(methylthio)thieno[ 2,3-e][1,4,2]dithiazine 1,1-dioxide (7a) with sulfuryl chloride produced 3,6-dichlorothieno[2,3- e][1,4,2]dithiazine 1,1-dioxide (10). The latter compound was used as a substrate for the preparation of N-alkyl- (or aryl)-6-chlorothieno[2,3-e][1,4,2]dithiazin-3-amine 1,1-dioxides 3a - c representing a new approach for the synthesis of similar derivatives. Compounds 7a - e showed modest to low antibacterial activity against E. coli and S. aureus.