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【结 构 式】 
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【分子编号】65764 【品名】Bis(2-nitrophenyl) disulfide; 2-Nitrophenyl disulfide; 2,2'-Dinitrodiphenyl disulfide 【CA登记号】1155-00-6 |
【 分 子 式 】C12H8N2O4S2 【 分 子 量 】308.3386 【元素组成】C 46.74% H 2.62% N 9.09% O 20.76% S 20.8% |
合成路线1
该中间体在本合成路线中的序号：(XIV)The precursor 4-fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide (VII) can be prepared by the following methods:
Condensation of 2-fluorobenzenethiol (X) with iodotriluoromethane in the presence of triethylamine and methyl viologen (1,1’-dimethyl-4,4’-bipyridinium dichloide) yields the trifluoromethyl sulfide (XI), which is oxidized to sulfone (XII) by means of NaIO4 and catalytic RuCl3 (1, 2). Subsequent chlorosulfonation of (XII) with ClSO3H affords the acid chloride (XIII), which is finally converted to the target sulfonamide (VII) upon quenching with ammonium hydroxide in cold isopropanol (1-3). Scheme 2.
In an improved method, treatment of bis(o-nitro-phenyl)disulfide (XIV) with potassium trifluoroacetate in sulfolane at 180-230 °C provides the trifluoromethyl sulide (XV), which is oxidized to the corresponding sulfone derivative (XVI) using periodic acid and a catalytic amount of CrO3. Finally, compound (XIV) is submitted to nitro group displacement with dried potassium fluoride and tetraphenylphosphonium bromide in hot DMSO (3). Scheme 2.
| 【1】 Bruncko, M., Ding, H., Elmore, S.W. et al. (Abbott Laboratories Inc.). Apoptosis promoters. EP 1888550, US 2007027135, US 7390799, WO 2007040650. |
| 【2】 Ding, H., Park, C.-M., Bruncko, M. et al. ABT-263, an orally bioavailable inhibitor of Bcl-2 family proteins. 235th ACS Natl Meet (April 6-10, New Orleans) 2008, Abst MEDI 110. |
| 【3】 Zhang, H., Zhou, J., Ha, C., Pei, D., Ding, K. An efficient synthesis of ABT-263, a novel inhibitor of antiapoptotic Bcl-2 proteins. Synthesis 2008, (15): 2398-404. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 65757 | 4-Fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide | 1027345-08-9 | C7H5F4NO4S2 | 详情 | 详情 |
| (X) | 65760 | 2-Fluorothiophenol; 2-Fluorobenzenethiol | 2557-78-0 | C6H5FS | 详情 | 详情 |
| (XI) | 65761 | 1-Fluoro-2-[(Trifluoromethyl)Thio]Benzene; 1-Fluoro-2-(Trifluoromethylthio)Benzene; 2-Fluorophenyl Trifluoromethyl Sulphide | 1978-16-1 | C7H4F4S | 详情 | 详情 |
| (XII) | 65762 | 2-Fluorophenyl trifluoromethyl sulfone; 1-Fluoro-2-(trifluoromethylsulfonyl)benzene | 2358-41-0 | C7H4F4O2S | 详情 | 详情 |
| (XIII) | 65763 | 4-Fluoro-3-(trifluoromethylsulfonyl)benzenesulfonyl Chloride | 1027345-07-8 | C7H3ClF4O4S2 | 详情 | 详情 |
| (XIV) | 65764 | Bis(2-nitrophenyl) disulfide; 2-Nitrophenyl disulfide; 2,2'-Dinitrodiphenyl disulfide | 1155-00-6 | C12H8N2O4S2 | 详情 | 详情 |
| (XV) | 65765 | 2-(trifluoromethylthio)nitrobenzene; 1-nitro-2-[(trifluoromethyl)thio]Benzene | 1644-87-7 | C7H4F3NO2S | 详情 | 详情 |
| (XVI) | 65766 | 1-Nitro-2-(trifluoromethylsulfonyl)benzene | 384-37-2 | C7H4F3NO4S | 详情 | 详情 |