2,6-Dichloro thiophenol; 2,6-Dichlorobenzenethiol; 2,6-Dichlorophenylhydrosulfide -Drug Synthesis Database

【结构式】

【分子编号】33293

【品名】2,6-Dichloro thiophenol; 2,6-Dichlorobenzenethiol; 2,6-Dichlorophenylhydrosulfide

【CA登记号】24966-39-0

【分子式】C₆H₄Cl₂S

【分子量】179.06916

【元素组成】C 40.24% H 2.25% Cl 39.6% S 17.91%

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：(C)

The chlorohydrin (II) is obtained by the reaction of p-chlorobenzylmagnesium chloride (I) with epichlorohydrin (A) in ether. This is then converted to the crystalline alcohol (III) by reaction with sodium imidazole (B) in DMF. On treatment with thionyl chloride is converted to the corresponding chloro compound (IV). When (IV) is reacted with 2,6-dichloro thiophenol (C) in the presence of anhydrous potassium carbonate in acetone, the free base of butoconazole is formed. Neutralization of the free base (V) with nitric acid gives butoconazole.

参考文献中间体

合成目标

【1】 Walker, K.A.M.; et al.; 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenylthio)n-butil]-1H-imidazole nitrate, a new patent antifungal agent. J Med Chem 1978, 21, 8, 840.
【2】 Arya, V.P.; Butoconazole nitrate. Drugs Fut 1979, 4, 2, 89.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(B)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(I)	33290	Bromo(4-chlorobenzyl)magnesium; p-Chlorobenzylmagnesium chloride		C₇H₆BrClMg	详情	详情
(II)	33291	1-chloro-4-(4-chlorophenyl)-2-butanol		C₁₀H₁₂Cl₂O	详情	详情
(III)	16486	4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol		C₁₃H₁₅ClN₂O	详情	详情
(IV)	33292	1-[2-chloro-4-(4-chlorophenyl)butyl]-1H-imidazole		C₁₃H₁₄Cl₂N₂	详情	详情
(V)	33294	1-[4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)sulfanyl]butyl]-1H-imidazole; 3-(4-chlorophenyl)-1-(1H-imidazol-1-ylmethyl)propyl 2,6-dichlorophenyl sulfide		C₁₉H₁₇Cl₃N₂S	详情	详情
(C)	33293	2,6-Dichloro thiophenol; 2,6-Dichlorobenzenethiol; 2,6-Dichlorophenylhydrosulfide	24966-39-0	C₆H₄Cl₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

2,6-Dichlorobenzenethiol (I) is oxidized to the sulfonyl chloride (II) employing N-chlorosuccinimide. Subsequent treatment of acid chloride (II) with ammonia in cold pyridine provides sulfonamide (III). Reaction of (III) with HNO3 in the presence of concentrated H2SO4 leads to the nitro derivative (IV). Then, displacement of one chloride group of (IV) with potassium acetate in the presence of crown ether gives rise to the acetate ester (V), which is further hydrolyzed to phenol (VI) under acidic conditions. Nitro group reduction in (VI) with H2 and Pd/C affords aniline (VII). Finally, coupling of (VII) with 2,3-dichlorophenyl isocyanate (VIII) produces the title diaryl urea.

参考文献中间体

合成目标

【1】 Widdowson, K.L.; Jin, Q.; McCleland, B.W.; Palovich, M.R. (GlaxoSmithKline Inc.); Hydroxy diphenyl urea sulfonamides as IL-8 receptor antagonists. EP 1161232; JP 2002532419; US 6500863; WO 0035442 .

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)	33293	2,6-Dichloro thiophenol; 2,6-Dichlorobenzenethiol; 2,6-Dichlorophenylhydrosulfide	24966-39-0	C₆H₄Cl₂S	详情	详情
(II)	65084	2,6-dichlorobenzenesulfonyl chloride		C₆H₃Cl₃O₂S	详情	详情
(III)	65085	2,6-dichlorobenzenesulfonamide		C₆H₅Cl₂NO₂S	详情	详情
(IV)	65086	2,6-dichloro-3-nitrobenzenesulfonamide		C₆H₄Cl₂N₂O₄S	详情	详情
(V)	65087	2-(aminosulfonyl)-3-chloro-6-nitrophenyl acetate		C₈H₇ClN₂O₆S	详情	详情
(VI)	65088	6-chloro-2-hydroxy-3-nitrobenzenesulfonamide		C₆H₅ClN₂O₅S	详情	详情
(VII)	65089	3-amino-6-chloro-2-hydroxybenzenesulfonamide		C₆H₇ClN₂O₃S	详情	详情
(VIII)	28667	1,2-dichloro-3-isocyanatobenzene	41195-90-8	C₇H₃Cl₂NO	详情	详情

Extended Information