2-nitrobenzenethiol; 2-nitrophenylhydrosulfide -Drug Synthesis Database

【结构式】

【分子编号】62460

【品名】2-nitrobenzenethiol; 2-nitrophenylhydrosulfide

【CA登记号】

【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 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XLIV)

The key cis glycidate ester (XLIII) was prepared by (salen)Mn(III)-catalyzed asymmetric epoxidation of the cis cinnamate (XXXIX). Epoxide opening in (XLIII) with 2-nitrothiophenol (XLIV), with inversion of the configuration, led to the nitro ester adduct (XLV). The nitro group of (XLV) was then reduced to the aniline derivative (XLVI) by means of FeSO4. Subsequent isopropyl ester group saponification in (XLVI) furnished amino acid (XXIX). This was then cyclized to the target thiazepinone (VIII) in refluxing xylene

参考文献中间体

合成目标

【1】 Jacobsen, E.N.; Deng, L.; Furukawa, Y.; Martinez, L.E.; Enantioselective catalytic epoxidation of cinnamate esters. Tetrahedron 1994, 50, 15, 4323.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	62502	4-Picoline N-oxide; 4-Methyl-1-pyridiniumolate	1003-67-4	C₆H₇NO	详情	详情
(VIII)	62436	(2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one		C₁₆H₁₅NO₃S	详情	详情
(XXIX)	62448	(2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoic acid		C₁₆H₁₇NO₄S	详情	详情
(XXXIX)	62458	isopropyl (Z)-3-(4-methoxyphenyl)-2-propenoate		C₁₃H₁₆O₃	详情	详情
(XLIII)	62459	isopropyl (2R,3R)-3-(4-methoxyphenyl)-2-oxiranecarboxylate		C₁₃H₁₆O₄	详情	详情
(XLIV)	62460	2-nitrobenzenethiol; 2-nitrophenylhydrosulfide		C₆H₅NO₂S	详情	详情
(XLV)	62461	isopropyl (2S,3S)-2-hydroxy-3-(4-methoxyphenyl)-3-[(2-nitrophenyl)sulfanyl]propanoate		C₁₉H₂₁NO₆S	详情	详情
(XLVI)	62462	isopropyl (2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-hydroxy-3-(4-methoxyphenyl)propanoate		C₁₉H₂₃NO₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXIII)

. 4-Hydroxycinnamic acid (XV) was acetylated with Ac2O in pyridine, and the resultant 4-acetoxycinnamic acid (XVI) was converted to the cinnamyl alcohol (XVIII) via conversion to the mixed anhydride (XVII) and subsequent reduction with NaBH4. Sharpless asymmetric epoxidation of (XVIII) furnished the chiral epoxide alcohol (XIX). After oxidation of alcohol (XIX) to the glycidic acid (XX) by means of RuO2/NaIO4, treatment with dimethyl sulfate and Et3N gave rise to the corresponding methyl ester (XXI). Epoxide opening in (XXI) with HCl and pyridine hydrochloride produced chlorohydrin (XXII) as a mixture of the desired (2S,3R)-isomer and minor amounts of the corresponding 3-chloro epimer. Condensation of (XXII) with 2-nitrothiophenol (XXIII) provided, after recrystallization from EtOH, the pure (S,S)-thioether adduct (XXIV). The hydroxyl group of (XXIV) was then protected as the methoxymethyl ether (XXV) by means of methylal in the presence of P2O5

参考文献中间体

合成目标

【1】 Honma, T.; Igarashi, K. (Shionogi & Co. Ltd.); Process for production of diltiazem hydrochloride. US 4552695 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	37809	(E)-3-(4-Hydroxyphenyl)-2-propenoic acid; 4-Hydroxy cinnamic acid	501-98-4	C₉H₈O₃	详情	详情
(XVI)	62479	(E)-3-[4-(acetyloxy)phenyl]-2-propenoic acid		C₁₁H₁₀O₄	详情	详情
(XVII)	62480			C₁₄H₁₄O₆	详情	详情
(XVIII)	62481	4-[(E)-3-hydroxy-1-propenyl]phenyl acetate		C₁₁H₁₂O₃	详情	详情
(XIX)	62482	4-[(2S,3S)-3-(hydroxymethyl)oxiranyl]phenyl acetate		C₁₁H₁₂O₄	详情	详情
(XX)	62483	(2R,3S)-3-[4-(acetyloxy)phenyl]-2-oxiranecarboxylic acid		C₁₁H₁₀O₅	详情	详情
(XXI)	62484	methyl (2R,3S)-3-[4-(acetyloxy)phenyl]-2-oxiranecarboxylate		C₁₂H₁₂O₅	详情	详情
(XXII)	62485	methyl (2S)-3-[4-(acetyloxy)phenyl]-3-chloro-2-hydroxypropanoate		C₁₂H₁₃ClO₅	详情	详情
(XXIII)	62460	2-nitrobenzenethiol; 2-nitrophenylhydrosulfide		C₆H₅NO₂S	详情	详情
(XXIV)	62486	methyl (2S,3S)-3-[4-(acetyloxy)phenyl]-2-hydroxy-3-[(2-nitrophenyl)sulfanyl]propanoate		C₁₈H₁₇NO₇S	详情	详情
(XXV)	62473	methyl (2S,3S)-3-[4-(acetyloxy)phenyl]-2-(methoxymethoxy)-3-[(2-nitrophenyl)sulfanyl]propanoate		C₂₀H₂₁NO₈S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The racemic precursor threo-hydroxy nitro ester (III), prepared by addition of 2-nitrothiophenol (II) to the racemic trans-glycidate (I), has been optically resolved by enantioselective lipase-catalyzed esterification of the (R,R)-isomer, producing the (R,R)-acetate (IV), while leaving unaltered the target intermediate, the (S,S)-hydroxy nitroester enantiomer (V). The racemic hydroxy nitro ester (III) has also been resolved through formation of the diastereoisomeric salts with L-lysine

参考文献中间体

合成目标

【1】 Kanerva, L.T.; Sundholm, O.; Lipase catalysis in the resolution of racemic intermediates of diltiazem synthesis in organic solvents. J Chem Soc - Perkins Trans I 1993, 13, 1385.
【2】 Senuma, M.; Shibazaki, M.; Nishimoto, S.; Shibata,K.; Okamura, K.; Date, T.; The practical resolution of (2RS,3RS)-2-hydroxy-3-(4-methoxyphenyl)-3-(2-nitrophenylthio)propionic acid, a key intermediate for diltiazem, with L-lysine. Chem Pharm Bull 1989, 37, 12, 3204.

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)	11907	Dimethylaminoethyl chloride; 2-Dimethylaminoethyl chloride; 2-Chloro-N,N-dimethyl-1-ethanamine; N-(2-Chloroethyl)-N,N-dimethylamine	107-99-3	C₄H₁₀ClN	详情	详情
(II)	62460	2-nitrobenzenethiol; 2-nitrophenylhydrosulfide		C₆H₅NO₂S	详情	详情
(III)	62471	methyl 2-hydroxy-3-(4-methoxyphenyl)-3-[(2-nitrophenyl)sulfanyl]propanoate		C₁₇H₁₇NO₆S	详情	详情
(IV)	62472	methyl (2R,3R)-2-(acetyloxy)-3-(4-methoxyphenyl)-3-[(2-nitrophenyl)sulfanyl]propanoate		C₁₉H₁₉NO₇S	详情	详情
(V)	63417	methyl (2S,3S)-2-hydroxy-3-(4-methoxyphenyl)-3-[(2-nitrophenyl)sulfanyl]propanoate		C₁₇H₁₇NO₆S	详情	详情

Extended Information