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【结 构 式】 
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【分子编号】32200 【品名】1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanone 【CA登记号】46503-52-0 |
【 分 子 式 】C11H8Cl2N2O 【 分 子 量 】255.1028 【元素组成】C 51.79% H 3.16% Cl 27.79% N 10.98% O 6.27% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of 2',4'-dichloro-2-imidazol-1-yl-acetophenone (I) with hydroxylamine (II) in refluxing ethanol pyridine gives the corresponding oxime (III). which is condensed with 2,4-dichlorobenzyl chloride (IV) by means of NaH in hot DMF.
| 【1】 Thiele, K.; Mixich, G.; Ein beitrag zur stereospezifischen Synthese von antimykotisch wirksamen imidazolyloximathern. Arzneim-Forsch Drug Res 1979, 29, 10, 1510-13. |
| 【2】 Mixich, G.; et al. (Siegfried AG); Imidazolyl-oxime ethers having anti-mycotic and bactericidal activity. DE 2657578; FR 2336129; GB 1514870; JP 52102276; US 4124767 . |
| 【3】 Serradell, M.N.; Blancafort, P.; Hillier, K.; Castaner, J.; Oxiconazole nitrate. Drugs Fut 1981, 6, 2, 99. |
| 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) | 32200 | 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanone | 46503-52-0 | C11H8Cl2N2O | 详情 | 详情 |
| (II) | 32201 | Hydroxylamine | 7803-49-8 | H3NO | 详情 | 详情 |
| (III) | 32202 | 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanone oxime | C11H9Cl2N3O | 详情 | 详情 | |
| (IV) | 18345 | 2,4-Dichlorobenzyl chloride; 2,4-Dichloro-1-(chloromethyl)benzene | 94-99-5 | C7H5Cl3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The reaction of 2,4-dichlorophenacyl chloride (I) with imidazole (A) gives the ketone (II), which is reduced with sodium borohydride to yield the alcohol (III). Conversion of the alcohol (III) to the chloro derivative (IV) with thionylchloride followed by reaction with p-chlorobenzyl mercaptan (V) affords sulconazole.
| 【1】 Keisu, E.E. U.; Manufacture of novel imidazole derivative. AT 347449B; BE 0833614; JP 59089667; ZA 7505100 . |
| 【2】 Arya, V.P.; Sulconazole. Drugs Fut 1980, 5, 4, 206. |
| 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) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
| (I) | 31092 | 2,2',4'-trichloroacetophenone; 2-chloro-1-(2,4-dichlorophenyl)-1-ethanone | 4252-78-2 | C8H5Cl3O | 详情 | 详情 |
| (II) | 32200 | 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanone | 46503-52-0 | C11H8Cl2N2O | 详情 | 详情 |
| (III) | 14550 | 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanol; alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol; 1-(2',4'-Dichlorophenyl)-2-(1-imidazolyl)ethanol | 24155-42-8 | C11H10Cl2N2O | 详情 | 详情 |
| (IV) | 32673 | 1-[2-chloro-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole | C11H9Cl3N2 | 详情 | 详情 | |
| (V) | 32674 | (4-chlorophenyl)methanethiol; 4-chlorobenzylhydrosulfide | 6258-66-8 | C7H7ClS | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XII)The bromination of 2,4-dichloroacetophenone (X) with Br2 in refluxing methanol gives 2,4-dichlorophenacyl bromide (XI), which is condensed with 1H-imidazole (IX) in methanol to yield 2,4-dichloro-alpha-(1-imidazolyl)acetophenone (XII). The reduction of (XII) with NaBH4 in refluxing methanol affords 1-(2,4-chlorophenyl)-2-(1-imidazolyl)ethanol (XIII), which is finally alkylated with allyl chloride (IV) and NaH in refluxing DMF.
| 【1】 Serradell, M.N.; Blancafort, P.; Castaner, J.; de Angelis, L.; Imazalil. Drugs Fut 1982, 7, 4, 254. |
| 【2】 Godefroi, E.F.; Schuermans, J.L.; US 3658813 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 13235 | Allyl chloride; 3-Chloro-1-propene | 107-05-1 | C3H5Cl | 详情 | 详情 |
| (IX) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
| (X) | 36407 | 1-(2,4-dichlorophenyl)-1-ethanone; 2',4'-dichloroaetophenone | 2234-16-4 | C8H6Cl2O | 详情 | 详情 |
| (XI) | 36408 | 2-bromo-1-(2,4-dichlorophenyl)-1-ethanone | C8H5BrCl2O | 详情 | 详情 | |
| (XII) | 32200 | 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanone | 46503-52-0 | C11H8Cl2N2O | 详情 | 详情 |
| (XIII) | 14550 | 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanol; alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol; 1-(2',4'-Dichlorophenyl)-2-(1-imidazolyl)ethanol | 24155-42-8 | C11H10Cl2N2O | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)
| 【1】 Foguet R, Ramentol J. Guglietta A. et al. 2003. Preparation of R-(一）-1-[2-(7-chlorobenzo.[b] thiophen-3-yl-methoxy)-2-(2,4-dichlorophenyl)-ethyl}lH-imidazole,i,e. R-(-)-sertaconuole, for the treatment of fungal infections．W0 2003068770(本专利属于Ferrer Intemacional S A，Spain) |