26386-88-9/疊氮磷酸二苯酯(DPPA)

疊氮磷酸二苯酯

英文名：Diphenylphosphoryl azide，簡(jiǎn)稱：DPPA。

CAS:[26386-88-9]

是由氯磷酸二苯酯與疊氮化鈉反應(yīng)得到的安全、高效的疊氮化試劑，可替代有爆炸風(fēng)險(xiǎn)的疊氮化鈉用于疊氮化反應(yīng)。

DPPA可與羧酸反應(yīng)，形成酰基疊氮中間體，并進(jìn)而與醇或胺反應(yīng)，形成N-取代氨基甲酸酯或酰胺。

一些無(wú)法通過Schmidt反應(yīng)制備N-取代氨基甲酸酯的羧酸，可利用DPPA這一特性來(lái)達(dá)到目的；而DPPA的成酰胺反應(yīng)，則使其在多肽合成中作為縮合劑而占有一席之地。

DPPA和活性醇反應(yīng)制備疊氮化物

利用DPPA通過Mitsunobu反應(yīng)可以取代羥基合成疊氮化物，但Mitsunobu反應(yīng)會(huì)生成大量的副產(chǎn)物，不易純化。

下面介紹一種可以得到相同產(chǎn)物的方法，利用DPPA和DBU，可以取代羥基得到構(gòu)型翻轉(zhuǎn)的疊氮化物，此反應(yīng)生成副產(chǎn)物磷酸二苯酯和DBU鹽都可以用水洗掉，可以很好的避免消除產(chǎn)物。但此反應(yīng)，只對(duì)于活性醇（芐醇或羧酸α位羥基）效果較好。

反應(yīng)機(jī)理

在DBU堿性條件下醇和DPPA反應(yīng)得到磷酸酯，取代下來(lái)的DBU疊氮鹽對(duì)磷酸酯進(jìn)行SN2反應(yīng)，構(gòu)型翻轉(zhuǎn)。

General Procedure: A mixture of the alcohol (10 mmol) and diphenylphosphoryl azide (3.3 g，12 mmol) were dissolved in dry solvent (18 ml). To the mixture at 0°c,under N2 was added neat 1,8- diazabicyclo[5.4.0]undec-7-ene (1.8 ml,12 mmol).The reaction was warmed to room temperature and stirred until complete. The resulting two phase mixture was washed with H2O (2 x 10 ml) and 5% HC1 (10 ml). The organic phase was concentrated in vacuum and purified by silica gel chromatography using 95:5(v:v) hexane: ethyl acetate.

(S)-(+)-ethyl lactate (2.54 g，21.5 mmol) and DPPA (7 g，25.4 mmol) were reacted with DBU (3.1 ml，20.7 mmol) in THF (35 ml) at 20C for 48 h. The batch was diluted with 5:1 hexane:ethyl acetate (120 ml) and washed with H2O (2x 40 mL) and 5%HCl (40 mL). The yield by HPLC assay was 87%.HPLC conditions [CH3CN:H20 gradient elution from 50:50 to 70:30 in 15 min,flow =1.5 ml/min,U.V.detection at 210 nm] RT 4,,5 min. The batch was concentrated and distilled to afford 2.2 gm (72%)of the volatile azide.

參考文獻(xiàn)

J. Org. Chem.,1993,58(22), pp 5886–5888