- A+
芳香磺酸或盐可以用一些氯化试剂比如五氯化磷,三氯氧磷,二氯化砜,氯磺酸,双光气,三光气,草酰氯等处理得到芳香磺酰氯。这几种氯磺化试剂各有优缺点,五氯化磷,三氯氧磷反应效果较好,但是后处理比较繁琐,反应温度要求较高。而二氯化砜后处理方便,往往蒸掉溶剂就可以直接投入下一步反应。另外磺酸甲酯也可以通过和NCS反应制备得到磺酰氯,但产率不高。
反应实例
A mixture of 2,5-dichloro-4-fluorobenzenesulfonic acid (3.51 g, 1 1.4 mmol) and phosphorus pentachloride (7.77 g, 37.3 mmol) were heated at 110 ℃ overnnight. After cooling down to room temperature, the reaction mixture was carefully poured into ice (50 g) The resulting mixture was stirred at room temperature for 30 min followed by addition of EA (100 ml_). The ethyl acetate layer was isolated and concentrated under vacuum to give the title compound as a yellow oil (3.51 g, 92percent).
【Patent: GLAXO GROUP LIMITED; WO2009/26197; (2009); (A1)English】
General procedure: At 0°C under argon atmosphere the phosphorus oxychloride (60eq, 107.28mmol) was added to compound 32 or 33 (1eq, 1.76mmol). The mixture was stirred 1h at 0°C then overnight at room temperature. After completion of the reaction, the mixture was poured to 100mL of iced water. The precipitate was filtrated and the residue was rinsed with water and cyclohexane to give the corresponding sulfonyl chloride derivative 34 or 35. 1 4-{[(4-Chloro-2-nitrophenyl)carbamoyl]amino}
benzene-1-sulfonyl chloride 34 white powder. Yield = 76percent.
【Benmansour, Fatiha; Trist, Iuni; Coutard, Bruno; Decroly, Etienne; Querat, Gilles; Brancale, Andrea; Barral, Karine; European Journal of Medicinal Chemistry; vol. 125; (2017); p. 865 - 880】
4-acetamidonaphthalene-l-sulfonic acid (5 g, 19 mmol) was slowly added to chlorosulfonic acid (25 ml) at 0℃. The mixture was allowed to warm to RT over 30 minutes and then stirred for 2 h. After slowly adding the reaction mixture to ice water, a fine yellow precipitate formed which was filtered, washed with water and dried under vacuum to give 4-acetamidonaphthalene-l-sulfonyl
chloride (4.73 g, 87percent).
【Patent: VERTEX PHARMACEUTICALS INCORPORATED; WO2007/30618; (2007); (A2) English】
To a 5 L flask was charged crude 4-(4-chloro-2-cyanophenyl)benzene-1-sulfonic acid (366.3 g, containing 289 g 4-(4-chloro-2-cyanophenyl)benzene-1-sulfonic acid, 0.98 mol) and toluene (3000 mL). Thionyl chloride (423 mL, 5.83 mol) was added dropwise followed by dimethylformamide (5 mL, 0.0646 mol). The reaction mixture was heated to75°C and stirred overnight. The reaction mixture was cooled, concentrated in vacuo, and the residue was partitioned between ethyl acetate (3000 mL) and water (1500 mL) and the organic layer washed with saturated brine (1500 mL). The organic layer was dried over anhydrous magnesium sulphate (50 g) and filtered. The residue was washed with ethyl acetate (2 x 100 mL) and the combined organic layers concentrated
to afford thetitle compound (297.6 g, 93percent yield) as a yellow solid.
【Patent:PIMCO 2664 LIMITED; PATEL, Lisa; SMITH, Stephen Allan; GREIG, Iain Robert; WILLIAMS, Samuel Cameron;WO2014/207445; (2014); (A1) English】
2-Diazo-1-naphthoquinone-4-sulfonic acid sodium salt (2.72g; 0.01mol) was taken into 25 ml of dichloromethane and cooled to -50 DEG C. Added triethylamine (2.02g; 0.02mol) to the above solution and maintained the temperature at -50 DEG C.Then added diphosgene (2.18g; 0.011mol) in 15 ml dichloromethane very slowly and maintaining the temperature at -50 DEG C with stirring over a period of 20min. The reaction mixture was stirred magnetically for 60 min at -50 DEG C. Reaction mixture was brought to room temperature and then dichloromethane and triethylamine was removed under vacuum. The remaining yellow powder was poured into ice water after 5 min of holding it in ice water the precipitate formed was filtered, washed with ice water and dried in a vacuum desiccator. The dried 2-diazo-1-naphthoquinone-4-sulfonylchloride weight was 2.14g(0.0080mol) yield 80percent m.p 138 -140 DEG C.
【Patent; COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH; EP1348693; (2003); (A1) English】
A vigourously stirred solution of 4- (2-OXO-4-TRIFLUOROMETHYL-1, 2- DIHYDROQUINOLIN-6-YLMETHYL) -BENZENESULFONIC ACID(1.92 g, 5.0 mmol) in anhydrous CH2C12-DMF (2: 1,60 mL) was treated dropwise with a solution of (COC1) 2 (3.17g, 25.0 mmol) in anhydrous CH2C12 (47 ML). When LCMS indicated the reaction was complete, the solution was concentrated
the residue dissolved in Et2O (250 ML). The ET20 solution was washed with H20 (80 ML), back-extracting with more Et2O (80ML). The combined organic extracts were dried (MGS04), filtered, concentrated. The residue was treated with PE the title compound (1.41 g, 70percent) collected: M/Z (ES+) = 402.1 [M + H] +
【Patent; WARNER-LAMBERT COMPANY LLC; WO2004/101544; (2004); (A1) English】
Methyl quinoline-6-sulfonate obtained above was dissolved in CH2CI2 (15.00 mL) at 0 °C. Then NCS (0.20 g, 1.52 mmol) was added. The reaction was stirred for 2 h. The reaction was quenched with brine then allowed to warm up to room temperature. The organic layer was separated and aqueous layer was washed with DCM. The combined organic layers were washed with water and brine, dried over Na2S04, filtered and concentrated. The residue was purified by silica gel column chromatography to give the title compound (199 mg, 57percent yield) as a beige solid。
【Patent; ARENA PHARMACEUTICALS, INC.; TRAN, Thuy-Anh; DO, Quyen-Quyen; ULLMAN, Brett; (259 pag.);WO2017/214002; (2017); (A1) English】
另外也有三聚氰氯用于此反应的报道。
【Blotny, Grzegorz; Tetrahedron Letters; vol. 44; nb. 7; (2003); p. 1499 - 1501】
化合物定制合成网推荐
目前评论:0