26386-88-9/疊氮磷酸二苯酯(DPPA)

疊氮磷酸二苯酯

英文名：Diphenylphosphoryl azide，簡稱：DPPA。

CAS:[26386-88-9]

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

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

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

DPPA和活性醇反應制備疊氮化物

利用DPPA通過Mitsunobu反應可以取代羥基合成疊氮化物，但Mitsunobu反應會生成大量的副產物，不易純化。

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

反應機理

在DBU堿性條件下醇和DPPA反應得到磷酸酯，取代下來的DBU疊氮鹽對磷酸酯進行SN2反應，構型翻轉。

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

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