三苯基膦作為縮合劑進(jìn)行酰胺化

三苯基磷-多鹵代甲烷( Synth.Commun ., 1990 , 1105)、三苯基磷-六氯丙酮( Tetrahedron lett. 1997 , 6489)、三苯基磷-NBS( Tetrahedron lett. 1997 , 5359)等也可以用于酰胺的縮合。與類(lèi)似 ，反應(yīng)的推動(dòng)力是三苯基氧膦的生成，其含有鍵能較強(qiáng)的 P=O 雙鍵，利于反應(yīng)進(jìn)行，三苯基氧膦作為好的離去基團(tuán)進(jìn)行酰胺化。

相關(guān)機(jī)理

機(jī)理和類(lèi)似。

反應(yīng)實(shí)例

2mmol of a carboxylic acid 37, 2 mmolof an amine 38, 2 mmol oftriethylamine, and 2 mmol of carbon tetrabromide are dissolved in 5 mL of drymethylene chloride. Solid triphenylphosphine (2 mmol, 554 mg) is then added portionwise over 5 min to the solutionstirred at room temperature. After afurther period of 10 min., the solvent is evaporated, and a 1:1 mixture ofhexane and ethyl acetate is added. Thesolid triphenyl phosphine oxide is filtered off, the solvents are evaporatedand the crude material can be purified by conventional methods.

【 Synth.Commun . , 1990 , 1105 】

A mixture of benzoic acid (122 mg, 1mmol) andhexachloroacetone (132 mg, 0.5 mmol) in methylene chloride (2 mL) was stirredunder argon and cooled down to -78℃. Triphenylphosphine (262 mg, 1 mmol) inmethylene chloride (1 mL) was added dropwise and the mixture was stirred for 20min. The acyl chloride solution was thentreated with a solution of benzylamine (107 mg, 1 mmol) in methylene chloride(1 mL) dropwise, followed by triethylamine (101 mg, 1mmol) in methylenechloride (1 mL) the reaction mixture wasthen allowed to reach room temperature after which the solvent was evaporated under highvacuum. The dry residue was suspended in20% ethyl acetate in hexane (4 mL) and silica gel added in order to obtain pasta. This pasta was added onto the top of a silicagel column and the elution performed with the same solvent. The pure fractions provided the titlecompound as a white solid (187 mg, 95%): m. p. 102℃.

【 Tetrahedron lett. 1997 , 6489 】

To a stirred solution of triphenylphosphine (2.55 mmol, 0.67 g) and hexanoic acid (2.5 mmol, 0.29 g) in anhydrous dichloromethane (5ml) at 0℃was added N-bromosuccinimide (NBS,2.8 mmol, 0.50 g) in one portion. The reaction mixture containing 0.25 mmol of 40 was thereafter set aside at roomtemperature while a new solution was being prepared: 3-Aminophenol (2.5 mmol, 0.28 g) and pyridine (3.20 mmol, 0.26 g) was dissolved in THF (5 ml). The mixture was cooled to about -25℃(ethanol/granular CO2), and vigorously stirred while the ready-made solution of40 was added dropwise. The cooling bath was removed after a few minand the temperature allowed to rise towards room temperature. Most of the solvents were removed under reducedpressure and the product purified by flash chromatography on Merck No. 9385 silica gel60, using ether as eluent. Removal ofthe solvent gave N-(3-hydroxyphenyl)-hexanamide41 (0.52 g, 98 %) as a colourless solid, m.p. 139-140℃. 1H NMR (200 MHz, acetone-d6): δ 0.90 (m, 3H, CH3), 1.35 (m, 4H, CH2), 1.65(m, 2H, CH2), 2.35 (t, 2H, CH2), 6.52 (m, IH, H ~o,~), 7.0 (m, 2H, H~om.), 7.42(s, 1H, H~o), 8.4 (s, 1H, OH), 9.05 (s, 1H, NH); MS (70 eV): m/z(%) 207 (17, M+),151 (6.5), 109 (100).

【 Tetrahedron lett. 1997 , 5359 】