利用三苯基膦溴化物制备脂肪溴代物
三苯基膦溴化物，如Ph3PX2和 Ph3P+CX3X-，在和醇进行溴置换反应时，具有活性高，反应条件温和等特点。由于反应中产生的溴化氢很少，因此不容易发生溴化氢引起的副反应。这两类试剂均可由三苯基膦与溴素或溴代烷直接制得，不经过分离纯化即可和醇进行反应。
反应机理
三苯基膦溴化物和醇反应生成烷氧基取代的三苯基膦加成物，后经溴素负离子的SN2反应，生成溴化物，同时发生构型翻转。
溴和三苯基膦
四溴化碳和三苯基膦
反应实例
反应一
To a solution of 1 (4 g, 22.5 mmol) in CH2Cl2(50 ml) at room temperature was added CBr4 (11.2 g, 34 mmol) followed by triphenylphosphine (8.8 g, 33 mmol). The reaction mixture wasallowed to stir for 2.5 h, and the solvent was removed under vacuum.Chromatography (30% EtOAc-hexanes) afforded 5.91 g (98%) of product 2 as an off-whitesolid.
【Journal of Medicinal Chemistry, 2004, 47, 15,3823-3842】
反应二
The alcohol (5.34 g, 16.7 mmol) and CBr4 (16.6 g, 50 mmol) were dissolved in 100 mlof dichloromethane. This solution was treated with solid triphenylphosphine (13.1 g, 50 mmol) over a 10 min period.This solution was allowed to stir for 18 h, and then 10 ml of ethanol wasadded. After 2 h this solution was treated with 100 ml of Et2O by dropwiseaddition over a 0.5 h period. The mixture was filtered, and the filtrate andwashings were trhen concentrated and purified by flash chromatography to give 4.79 g (74% yield) of the title compound.This material recrystallized (Et2O/hexane) on standing to give mp 87-88℃
【J.Org.Chem. 1991, 56, 9, 3009-3016】
反应三
Ina well-ventilated hood, a 2-L, three-necked,round-bottomed flask, equipped with a magneticstirrer, thermometer, dropping funnel, and a refluxcondenser, is charged under nitrogenwith 327 g (1.24 mol) of triphenylphosphine,and 1.24 L of anhydrous dichloromethane. The solution is vigorously stirred under acetone-dryice cooling, as 199 g (64.1 ml, 1.25 mol) of bromine is added over a period of 0.5 hr at −30°C to −15°C under nitrogen.After an additional 15 min of stirring, a mixture of 116 g(1.18 mol) of 1-cyclopropylcyclopropanoland 93.5 g (95.6 ml,1.18 mol) of anhydrous pyridineis added dropwise at −15°C over a period of 2 hours. The mixture is stirredat 20°C for an additional24 hours under nitrogen.The reflux condenser and the dropping funnel are removed. The flask is immersed in anoil bath and connected to a 2-L,two-necked, round-bottomed flask via a 90° angleglass tube. The second flask is cooled with acetone-dry ice. All thevolatile material is bulb-to-bulb distilled, at first under water-aspiratorvacuum and 30°C oil bath temperature, and then under further reducedpressure (0.1 mm) with a 100°C oil bath.The distillation is continued until the temperature in the first flask reaches 80°C. The receiver flask is allowed towarm to 20°C, and the solventis removed by distillation at atmospheric pressure using a 30-cm Vigreuxcolumn. The residue is distilled under reduced pressure to give 117.1 g (62%) of 1-bromo-1-cyclopropylcyclopropane.
【Organic Syntheses, Coll. Vol. 10,p.88; Vol. 78, p.142】
反应四
To a –30℃solution of cis-3-methyl-2-penten-4-yn-1-ol 1 (10 g, 104 mmol) in aanhydrous CH2Cl2(100 ml) was added Ph3P (32.73 g, 124.8 mmol) followed by freshly recrystallizedN-bromosuccinimide (22.2 g,124.8 mmol). After 3.5 h, the reaction mixture was diluted with ether (300 ml),warmed to room temperature, and washed with saturated aqueous Na2CO3solution (2 X 200 ml) and then brine (200 ml). The residue obtained afterdrying and evaporation in vacuo was triturated in petroleum ether (200 ml),filtered to remove precipitated triphenylphosphine oxide and succinimide,concentrated under reduced pressure, and chromatographed (petroleum ether) tofurnish 5-bromo-3-methylpent-cis-3-en-1-yne (13.56 g, 82%) as a colorless oil.
【 J.Org.Chem., 1995, 60, 22, 7209-7214】