合成路线:The synthesis of pipethiadene (VII) is carried out by four steps from phthalide (I) and 2-thio-phenethiol (II).A solution of the sodium salt of (II) in ethanol,prepared by dissolving (II) in ethanolic sodium ethoxide,is refluxed with (I) to give 2-(2-thienylthiomethyl)benzoic acid (III).A modified procedure for preparing (III) consists of using the crude products of reactions of 2-thienylmagnesium bromide or 2-thienylmagnesium iodide sulfur instead of the Na salt of (II).The acid (III) is then cyclized either with polyphosphoric acid in the presence of boiling toluene,with phosphorus pentoxide in boiling toluene or with phosphoric ethyl ester in toluene at 100 C.The ketone (IV) is then treated with 1-methyl-4-piperidylmagnesium chloride (A) in tetrahydrofuran and the resulting amino alcohol (V) is dehydrated with boiling dilute sulfuric acid to give the desired (VII).More recently it has been established that the expected formation of (V) is accompanied by a 1,6-addition with the subsequent air-oxidation producing the byproduct (VI).This compound melts precisely at the same temperature as compound (V),and it is necessary to separate it on the basis of its good solubility in ethanol,in which (V) is almost insoluble in the cold.Neutralization of the base (VII) with (+)-tartaric acid in ethanol affords pipethiadene (+)-tartrate.
参考文献标题:
文献作者:Protiva,M.; Rajsner,M.
参考来源:US 3519649
合成路线:The synthesis of pipethiadene (VII) is carried out by four steps from phthalide (I) and 2-thio-phenethiol (II).A solution of the sodium salt of (II) in ethanol,prepared by dissolving (II) in ethanolic sodium ethoxide,is refluxed with (I) to give 2-(2-thienylthiomethyl)benzoic acid (III).A modified procedure for preparing (III) consists of using the crude products of reactions of 2-thienylmagnesium bromide or 2-thienylmagnesium iodide sulfur instead of the Na salt of (II).The acid (III) is then cyclized either with polyphosphoric acid in the presence of boiling toluene,with phosphorus pentoxide in boiling toluene or with phosphoric ethyl ester in toluene at 100 C.The ketone (IV) is then treated with 1-methyl-4-piperidylmagnesium chloride (A) in tetrahydrofuran and the resulting amino alcohol (V) is dehydrated with boiling dilute sulfuric acid to give the desired (VII).More recently it has been established that the expected formation of (V) is accompanied by a 1,6-addition with the subsequent air-oxidation producing the byproduct (VI).This compound melts precisely at the same temperature as compound (V),and it is necessary to separate it on the basis of its good solubility in ethanol,in which (V) is almost insoluble in the cold.Neutralization of the base (VII) with (+)-tartaric acid in ethanol affords pipethiadene (+)-tartrate.
参考文献标题:Some new types of 6,11-dihydrodibenzo[b,e]thiepin derivatives and their analogues
文献作者:Rajsner,M.; Vejdelek,Z.J.; Protiva,M.; Seidlov? V.; Adlerov? E.
参考来源:Coll Czech Chem Commun 1964,292161
合成路线:The synthesis of pipethiadene (VII) is carried out by four steps from phthalide (I) and 2-thio-phenethiol (II).A solution of the sodium salt of (II) in ethanol,prepared by dissolving (II) in ethanolic sodium ethoxide,is refluxed with (I) to give 2-(2-thienylthiomethyl)benzoic acid (III).A modified procedure for preparing (III) consists of using the crude products of reactions of 2-thienylmagnesium bromide or 2-thienylmagnesium iodide sulfur instead of the Na salt of (II).The acid (III) is then cyclized either with polyphosphoric acid in the presence of boiling toluene,with phosphorus pentoxide in boiling toluene or with phosphoric ethyl ester in toluene at 100 C.The ketone (IV) is then treated with 1-methyl-4-piperidylmagnesium chloride (A) in tetrahydrofuran and the resulting amino alcohol (V) is dehydrated with boiling dilute sulfuric acid to give the desired (VII).More recently it has been established that the expected formation of (V) is accompanied by a 1,6-addition with the subsequent air-oxidation producing the byproduct (VI).This compound melts precisely at the same temperature as compound (V),and it is necessary to separate it on the basis of its good solubility in ethanol,in which (V) is almost insoluble in the cold.Neutralization of the base (VII) with (+)-tartaric acid in ethanol affords pipethiadene (+)-tartrate.
参考文献标题:Geometric isomerism of 4-(3-dimethylaminopropylidene)-9H-thieno[2,3-b]benzo[e]thiepin
文献作者:Metys,J.; Rajsner,M.; Sv醫ek,E.; Protiva,M.
参考来源:Coll Czech Chem Commun 1974,391366
合成路线:The synthesis of pipethiadene (VII) is carried out by four steps from phthalide (I) and 2-thio-phenethiol (II).A solution of the sodium salt of (II) in ethanol,prepared by dissolving (II) in ethanolic sodium ethoxide,is refluxed with (I) to give 2-(2-thienylthiomethyl)benzoic acid (III).A modified procedure for preparing (III) consists of using the crude products of reactions of 2-thienylmagnesium bromide or 2-thienylmagnesium iodide sulfur instead of the Na salt of (II).The acid (III) is then cyclized either with polyphosphoric acid in the presence of boiling toluene,with phosphorus pentoxide in boiling toluene or with phosphoric ethyl ester in toluene at 100 C.The ketone (IV) is then treated with 1-methyl-4-piperidylmagnesium chloride (A) in tetrahydrofuran and the resulting amino alcohol (V) is dehydrated with boiling dilute sulfuric acid to give the desired (VII).More recently it has been established that the expected formation of (V) is accompanied by a 1,6-addition with the subsequent air-oxidation producing the byproduct (VI).This compound melts precisely at the same temperature as compound (V),and it is necessary to separate it on the basis of its good solubility in ethanol,in which (V) is almost insoluble in the cold.Neutralization of the base (VII) with (+)-tartaric acid in ethanol affords pipethiadene (+)-tartrate.
参考文献标题:4,9-Dihyfrothieno[2,3-b]benzo[3]thiep靚 derivatives
文献作者:Metys,J.; Protiva,M.; Sv醫ek,E.; Rajsner,M.
参考来源:Coll Czech Chem Commun 1967,322854
合成路线:The synthesis of pipethiadene (VII) is carried out by four steps from phthalide (I) and 2-thio-phenethiol (II).A solution of the sodium salt of (II) in ethanol,prepared by dissolving (II) in ethanolic sodium ethoxide,is refluxed with (I) to give 2-(2-thienylthiomethyl)benzoic acid (III).A modified procedure for preparing (III) consists of using the crude products of reactions of 2-thienylmagnesium bromide or 2-thienylmagnesium iodide sulfur instead of the Na salt of (II).The acid (III) is then cyclized either with polyphosphoric acid in the presence of boiling toluene,with phosphorus pentoxide in boiling toluene or with phosphoric ethyl ester in toluene at 100 C.The ketone (IV) is then treated with 1-methyl-4-piperidylmagnesium chloride (A) in tetrahydrofuran and the resulting amino alcohol (V) is dehydrated with boiling dilute sulfuric acid to give the desired (VII).More recently it has been established that the expected formation of (V) is accompanied by a 1,6-addition with the subsequent air-oxidation producing the byproduct (VI).This compound melts precisely at the same temperature as compound (V),and it is necessary to separate it on the basis of its good solubility in ethanol,in which (V) is almost insoluble in the cold.Neutralization of the base (VII) with (+)-tartaric acid in ethanol affords pipethiadene (+)-tartrate.
参考文献标题:Antiaminic agents derived from thieno[2,3-c][2]benzothiepin: 4-(1-methyl-4-piperidylidene)-4,9-dihydroyhieno[2,3-c][2]benzothiepin and some related compounds
文献作者:Rajsner,M.; Protiva,M.; Metys,J.; Holubek,J.; Ryska,M.; Pol韛ka,Z.; Sv醫ek,E.
参考来源:Coll Czech Chem Commun 1983,48623
产品链接: CAS No. 73035-29-7›› 产品链接: CAS No.15053-99-3››