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Synthesis and transformations of 4,5‐dihydro‐1,4‐benzothiazepin‐3(2 H )‐one derivatives
Author(s) -
Szabó János,
Fodor Lajos,
Katócs Ágnes,
Bernáth Gábor,
Sohár Pál
Publication year - 1986
Publication title -
chemische berichte
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 0009-2940
DOI - 10.1002/cber.19861190922
Subject(s) - chemistry , sodium methoxide , acetonitrile , sodium ethoxide , medicinal chemistry , ring (chemistry) , hydroxymethyl , yield (engineering) , sodium , sulfoxide , methanol , organic chemistry , ethanol , materials science , metallurgy
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 ).