4-nitrophenylhydrosulfide; 4-nitrobenzenethiol -Drug Synthesis Database

【结构式】

【分子编号】38898

【品名】4-nitrophenylhydrosulfide; 4-nitrobenzenethiol

【CA登记号】1849-36-1

【分子式】C₆H₅NO₂S

【分子量】155.17724

【元素组成】C 46.44% H 3.25% N 9.03% O 20.62% S 20.66%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XI)

The reaction of 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose (I) with methanesulfonyl chloride and pyridine gives the mesylate (II), which by treatment with sodium azide in DMF is converted into 3-azido-3-deoxy-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose (III). Selective hydrolysis of (III) with 1N HCl in ethanol affords 3-azido-3-deoxy-1,2-O-isopropylidene-alpha-D-glucofuranose (IV) (1), which is oxidized with sodium metaperiodate to the aldehyde (V). The reduction of (V) with NaBH4 in EtOH gives 3-azido-3-deoxy-1,2-O-isopropylidene-alpha-D-xylofuranose (VI), which is treated with tosyl chloride and pyridine to yield the corresponding 5-O-tosylate (VII) (2). The reaction of (VII) with potassium thiobenzoate (VIII) in hot DMF gives 3-azido-5-S-benzoyl-3-deoxy-1,2-O-isopropylidene-5-thio-alpha-D-xylofuranose (IX), which is treated successively with NaOMe in methanol, to induce cyclization, with refluxing HCl in methanol, to eliminate the isopropylidene group, and finally with acetic anhydride to furnish 1,2,4-tri-O-acetyl-3-azido-3-deoxy-5-thio-D-xylopyranose (X). The condensation of (X) with 4-nitrothiophenol (XI) by means of trimethylsilyl triflate in dichloromethane yields the corresponding acylated dithiopyranoside, which is finally deacetylated with sodium methoxide in methanol.

参考文献中间体

合成目标

【1】 Meyer, W.; Synthese der 3-Amino-3-desoxy- und 3,6-Diamino-3,6-didesoxy-D-glucose. Chem Ber 1968, 101, 11, 3802-07.
【2】 Kuzuhara, H.; Ohrui, H.; Emoto, S.; Conversion of D-Glucose into d-Oxybiotin. Part I. Synthesis of 2,5-anhydro-3-azido-3-deoxy-D-xylose dimethyl acetal. Agr Biol Chem 1970, 34, 3, 375-380.
【3】 Kovácsné Bozó, E.; Kuszmann, J.; Szabó, G.; Boros, S.; Moravcsik, I. (Gedeon Richter Ltd.); Novel anticoagulant glycosides and pharmaceutical compsns. thereof. EP 0907656; WO 9749716 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	29141	(3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol	582-52-5	C₁₂H₂₀O₆	详情	详情
(II)	38930	(3aR,5R,6R,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-6-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]tetrahydrofuro[2,3-d][1,3]dioxole		C₁₅H₂₆O₆S	详情	详情
(III)	38931	(3aR,5S,6S,6aR)-6-azido-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole; (3aR,5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl azide		C₁₂H₁₉N₃O₅	详情	详情
(IV)	38932	(1R)-1-[(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]-1,2-ethanediol		C₉H₁₅N₃O₅	详情	详情
(V)	38933	(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole-5-carbaldehyde		C₈H₁₁N₃O₄	详情	详情
(VI)	38934	[(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methanol		C₈H₁₃N₃O₄	详情	详情
(VII)	38935	[(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl 4-methylbenzenesulfonate		C₁₅H₁₉N₃O₆S	详情	详情
(VIII)	38936	potassium benzenecarbothioate		C₇H₅KOS	详情	详情
(IX)	38937	S-[[(3aR,5S,6S,6aR)-6-azido-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]methyl] benzenecarbothioate		C₁₅H₁₇N₃O₄S	详情	详情
(X)	38938	(2R,3R,4S,5S)-2,5-bis(acetoxy)-4-azidotetrahydro-2H-thiopyran-3-yl acetate		C₁₁H₁₅N₃O₆S	详情	详情
(XI)	38898	4-nitrophenylhydrosulfide; 4-nitrobenzenethiol	1849-36-1	C₆H₅NO₂S	详情	详情
(XII)	38939	(2S,3R,4S,5S)-5-(acetoxy)-4-azido-2-[(4-nitrophenyl)sulfanyl]tetrahydro-2H-thiopyran-3-yl acetate		C₁₅H₁₆N₄O₆S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The thiobenzoylation of the readily available 2,3-O-isopropylidene-5-O-tosyl-L-arabinose diethyl dithioacetal (I) gives the 5-S-thiobenzoate (II), which is treated with HgO and BF3/Et2O in THF/water gives the corresponding aldehyde (III). The cyclization of (III) with NaOMe in methanol affords the cyclic arabinopyranose (IV), which is deprotected with AcOH giving 5-O-benzoyl-beta-D-arabinopyranose (V). The acetylation of (V) with Ac2O yields the triacetate (VI), which is condensed with 4-nitrothiophenol (VII) by means of K2CO3 in refluxing acetone affording the acylated dithio-beta-D-arabinopyranoside (VIII). Finally, this compound is deacylated with NaOMe in MeOH.

参考文献中间体

合成目标

【1】 Bozo, E.; Boros, S.; Kuszmann, J.; Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio-L- and -D-arabinopyranosides possessing antithrombotic activity. Carbohydr Res 1998, 311, 4, 191.
【2】 Szeker, G.; Boros, S.; Szabó, G.; Turuczné Ferwagner, M.; Orbán, O.; Feher, B.; Soukupné Kedves, R.; Kenyeres, L.; Kovácsné Bozó, E.; Barabás, É.; Moravcsik, I.; Kaszás, E.; Kuszmann, J. (Gedeon Richter Ltd.); Novel anticoagulant glycosides and pharmaceutical compsns. thereof. WO 9928312 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	38892	(2S)-2-[(4S,5R)-5-[bis(ethylsulfanyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethyl 4-methylbenzenesulfonate		C₁₉H₃₀O₆S₃	详情	详情
(II)	38893	S-((2R)-2-[(4S,5R)-5-[bis(ethylsulfanyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethyl) benzenecarbothioate		C₁₉H₂₈O₄S₃	详情	详情
(III)	38894	S-[(2R)-2-[(4S,5R)-5-formyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethyl] benzenecarbothioate		C₁₅H₁₈O₅S	详情	详情
(IV)	38895	(3aR,4R,7R,7aR)-4-hydroxy-2,2-dimethyltetrahydro-4H-thiopyrano[3,4-d][1,3]dioxol-7-yl benzoate		C₁₅H₁₈O₅S	详情	详情
(V)	38896	(3R,4R,5R,6R)-4,5,6-trihydroxytetrahydro-2H-thiopyran-3-yl benzoate		C₁₂H₁₄O₅S	详情	详情
(VI)	38897	(3R,4R,5R,6R)-4,5,6-tris(acetoxy)tetrahydro-2H-thiopyran-3-yl benzoate		C₁₈H₂₀O₈S	详情	详情
(VII)	38898	4-nitrophenylhydrosulfide; 4-nitrobenzenethiol	1849-36-1	C₆H₅NO₂S	详情	详情
(VIII)	38899	(3R,4R,5R,6S)-4,5-bis(acetoxy)-6-[(4-nitrophenyl)sulfanyl]tetrahydro-2H-thiopyran-3-yl benzoate		C₂₂H₂₁NO₈S₂	详情	详情

Extended Information