Synthesis of novel substituted 2-phenyl-4-esteryl-1,5-benzothiazepines

【作者】 Lin He； Minyue Zhang； 王兰芝；

【Author】 Lin He;Minyue Zhang;Lanzhi Wang;The College of Chemistry and Material Science Hebei Normal University;

【机构】 The College of Chemistry and Material Science Hebei Normal University； 河北师范大学；

【摘要】 1,5-benzothiazepines¹ are constitute valuable structural units for all sorts of important natural products, chemical products, pharmaceuticals, conjugated polymers and other materials.Many 1,5-benzothiazepines hold many medicinal applications like sedative, psychoactive drug, hypnotic agents, anticonvulsant², anti-depressive and anti-anxiety.By bring the –COOR,-Ph-COR active groups³ on the seven-membered heterocycle, a new 1,5-benzothiazepines can be obtained with higher biological activity.In view of our continuous interest in the synthesis of new benzothiazepine derivatives, we wished to examine the possibility of synthesis of 1,5-benzothiazepines incorporating free ester and phenyl moiety on the seven-membered ring structure.Thus we have designed and synthesized a series of novel substituted 2-phenyl-4-esteryl-1,5-benzothiazepines through three steps reaction.In accordance with Scheme 1, 2-oxo-4-phenyl-3-butenoic acids（1） are obtained via aldol condensation reaction of ethyl pyruvate with substituted benzaldehyde.And then,2-oxo-4-phenyl-3-butenoic acid ethyl esters（2） were synthesized via esterification reaction.Michael addition of o-aminothiophenol to 4-（substituted-phenyl）-2-oxo-3-butenoate yielded and the intramolecular cyclisation, followed by dehydration in PMA-SiO₂/ethanol provided 2-（substituted-phenyl）-4-ester-1,5-benzothiazepines, which were purified by crystallization from dry ethanol.After ending of the reaction（TLC）, compounds（3） were obtained in a pure state in 82–95% yields.Fifteen 2-（substituted-phenyl）-4-ester-1,5-benzothiazepines（Scheme 1） were synthesized successfully by simple reaction.Target compounds were characterized by ¹H NMR, ¹³C NMR, MS, and IR.The distinct advantages of our procedure are simple methodology, fast reaction rate and the PMA-SiO₂ catalyst was used directly four times without a considerable loss of its catalytic activity.更多还原

【Abstract】 1,5-benzothiazepines¹ are constitute valuable structural units for all sorts of important natural products, chemical products, pharmaceuticals, conjugated polymers and other materials.Many 1,5-benzothiazepines hold many medicinal applications like sedative, psychoactive drug, hypnotic agents, anticonvulsant², anti-depressive and anti-anxiety.By bring the –COOR,-Ph-COR active groups³ on the seven-membered heterocycle, a new 1,5-benzothiazepines can be obtained with higher biological activity.In view of our continuous interest in the synthesis of new benzothiazepine derivatives, we wished to examine the possibility of synthesis of 1,5-benzothiazepines incorporating free ester and phenyl moiety on the seven-membered ring structure.Thus we have designed and synthesized a series of novel substituted 2-phenyl-4-esteryl-1,5-benzothiazepines through three steps reaction.In accordance with Scheme 1, 2-oxo-4-phenyl-3-butenoic acids（1） are obtained via aldol condensation reaction of ethyl pyruvate with substituted benzaldehyde.And then,2-oxo-4-phenyl-3-butenoic acid ethyl esters（2） were synthesized via esterification reaction.Michael addition of o-aminothiophenol to 4-（substituted-phenyl）-2-oxo-3-butenoate yielded and the intramolecular cyclisation, followed by dehydration in PMA-SiO₂/ethanol provided 2-（substituted-phenyl）-4-ester-1,5-benzothiazepines, which were purified by crystallization from dry ethanol.After ending of the reaction（TLC）, compounds（3） were obtained in a pure state in 82–95% yields.Fifteen 2-（substituted-phenyl）-4-ester-1,5-benzothiazepines（Scheme 1） were synthesized successfully by simple reaction.Target compounds were characterized by ¹H NMR, ¹³C NMR, MS, and IR.The distinct advantages of our procedure are simple methodology, fast reaction rate and the PMA-SiO₂ catalyst was used directly four times without a considerable loss of its catalytic activity.更多还原