Synthesis and transformations of 4,5‐dihydro‐1,4‐benzothiazepin‐3(2 H )‐one derivatives

The attempted cyclization of S ‐(3,4‐dimethoxyphenyl)‐ N ‐(hydroxymethyl)thioglycolamide ( 6 ) with phosphoryl chloride gave, instead of the expected benzothiazepinone 7e , (3,4‐dimethoxyphenylthio)acetonitrile ( 8 ). The product of ring closure of N ‐[[2‐(benzoylthio)‐4,5‐dimethoxyphenyl]methyl]‐2‐chloroacetamide ( 11 ) with sodium ethoxide was 4,5‐dihydro‐7,8‐dimethoxy‐1,4‐benzothiazepin‐3(2 H )‐one ( 7e ). The latter compound can also be prepared in good yield from ethyl S ‐[2‐(aminomethyl)‐4,5‐dimethoxyphenyl]thioglycolate ( 15 ) in alkaline solution. The thiophenols 16a , b reacted with α‐halogenocarboxylic esters 17 in the presence of sodium methoxide to furnish the corresponding 4,5‐dihydro‐1,4‐benzothiazepin‐3(2 H )‐ones 7a – i in high yields in one step. Several conversions of these benzothiazepinones were effected; 3‐thiones 18a , b , sulfones 19a , b , sulfoxide 20 , N ‐benzoyl 22a and N ‐phenylcarbamoyl 22b derivatives were synthesized. LiAlH 4 reduction of 7e gave 2,3,4,5‐tetrahydro‐7,8‐dimethoxy‐1,4‐benzothiazepine ( 21 a ).