One-Pot Syntheses of 2-(2-Sulfanyl-4H-3,1-benzothiazin-4-yl) acetic Acid Derivatives via Reactions of 3-(2-Isothiocyanatophenyl)prop-2-enoic Acid Derivatives with Thiols or Sodium Sulfide

Two efficient methods for the preparation of 2-(2-sulfanyl-4H-3,1-benzothiazin-4-yl) acetic acid derivatives 3 under mild conditions have been developed. The first method is based on the reaction of 3( 2-isothiocyanatophenyl) prop-2-enoates 1a - 1c with thiols in the presence of Et(3)N in THF at room temperature, leading to the corresponding dithiocarbamate intermediates 2, which underwent spontaneous cyclization at the same temperature by an attack of the S-atom at the prop-2-enoyl moiety in a 1,4-addition manner (Michael addition) to give 2-(2-sulfanyl-4H-3,1-benzothiazin-4-yl)acetates in one pot. The second method involves treatment of 3-(2-isothiocyanatophenyl)prop-2-enoic acid derivatives 1b - 1d with Na(2)S leading to the formation of 2-(2-sodiosulfanyl-4H-3,1-benzothiazin-4-yl)acetic acid intermediates 5 by a similar addition/cyclization sequence, which are then allowed to react with alkyl or aryl halides to afford derivatives 3. 2-(2-Thioxo-4H-3,1-benzothiazin-4-yl)acetic acid derivatives 6 can be obtained by omitting the addition of halides.