【结 构 式】 |
【分子编号】35452 【品名】2-phenyl-4-(trifluoromethyl)-1H-imidazole 【CA登记号】 |
【 分 子 式 】C10H7F3N2 【 分 子 量 】212.1742696 【元素组成】C 56.61% H 3.33% F 26.86% N 13.2% |
合成路线1
该中间体在本合成路线中的序号:(V)The bromination of 1,1,1-trifluoroacetone (I) according to McBee and Burton gives 3,3-dibromo-1,1,1-trifluoroacetone (II), which is hydrolyzed with aqueous NaOAc to the glyoxal (III). The cyclization of (III) with benzaldehyde (IV) and ammonia in methanol yields 2-phenyl-4-(trifluoromethyl)-1H-imidazole (V), which is converted into the carbonitrile (VI) by reaction with hot aqueous ammonium hydroxide. The reduction of (VI) with diisobutylaluminum hydride in THF affords the carbaldehyde (VII), which is finally condensed with N-tert-butylhydroxylamine (VIII) by means of NaHCO3 in hot ethanol.
【1】 Dhainaut, A.; et al.; Synthesis, structure, and neuroprotective properties of novel imidazolyl nitrones. J Med Chem 2000, 43, 11, 2165. |
【2】 Dhainaut, A.; Lestage, P.; Lockhart, B.; Tizot, A.; Goldstein, S. (ADIR et Cie.); Nitrone derivs., process for their preparation and pharmaceutical compsns. containing them. CA 2274621; EP 0967207; FR 2780404; JP 2000026428; US 6034250 . |
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) | 35449 | 1,1,1-trifluoroacetone | 421-50-1 | C3H3F3O | 详情 | 详情 |
(II) | 35450 | 3,3-dibromo-1,1,1-trifluoroacetone | 431-67-4 | C3HBr2F3O | 详情 | 详情 |
(III) | 35451 | 3,3,3-trifluoro-2-oxopropanal | C3HF3O2 | 详情 | 详情 | |
(IV) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
(V) | 35452 | 2-phenyl-4-(trifluoromethyl)-1H-imidazole | C10H7F3N2 | 详情 | 详情 | |
(VI) | 35435 | (1R)-2-[12-[(2R)-2-(benzoyloxy)propyl]-2,4,6,7,9,11-hexamethoxy-3,10-dioxo-3,10-dihydro-1-perylenyl]-1-methylethyl benzoate | C46H42O12 | 详情 | 详情 | |
(VII) | 35454 | 2-phenyl-1H-imidazole-4-carbaldehyde | C10H8N2O | 详情 | 详情 | |
(VIII) | 35455 | N-(tert-butyl)hydroxylamine; 2-(hydroxyamino)-2-methylpropane | C4H11NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(I)The hydrolysis of 2-phenyl-4-(trifluoromethyl)-1H-imidazole (I) with 1N NaOH gives 2-phenyl-1H-imidazole-4-carboxylic acid (II), which is condensed with N,O-dimethylhydroxylamine (III) by means of TBTU and DIEA in dichloromethane to yield the amide (IV). The reduction of (IV) with DIBAL in THF affords 2-phenyl-1H-imidazole-4-carbaldehyde (V), which is finally condensed with N-tert-butylhydroxylamine (VI) by means of NaHCO3 in hot ethanol to provide the target nitrone.
【1】 Dhainaut, A.; et al.; Synthesis, structure, and neuroprotective properties of novel imidazolyl nitrones. J Med Chem 2000, 43, 11, 2165. |
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) | 35452 | 2-phenyl-4-(trifluoromethyl)-1H-imidazole | C10H7F3N2 | 详情 | 详情 | |
(II) | 51473 | 2-phenyl-1H-imidazole-4-carboxylic acid | C10H8N2O2 | 详情 | 详情 | |
(III) | 13361 | (Methoxyamino)methane; N,O-Dimethylhydroxylamine | 1117-97-1 | C2H7NO | 详情 | 详情 |
(IV) | 51474 | N-methoxy-N-methyl-2-phenyl-1H-imidazole-4-carboxamide | C12H13N3O2 | 详情 | 详情 | |
(V) | 35454 | 2-phenyl-1H-imidazole-4-carbaldehyde | C10H8N2O | 详情 | 详情 | |
(VI) | 35455 | N-(tert-butyl)hydroxylamine; 2-(hydroxyamino)-2-methylpropane | C4H11NO | 详情 | 详情 |