Diphenylphosphate azide
English name: Diphenylphosphoryl azide, abbreviation: DPPA.
CAS: [26386-88-9]
It is a safe and efficient azide reagent obtained from the reaction of diphenyl chlorophosphate and sodium azide. It can replace sodium azide with explosion risk for azide reaction.
DPPA can react with carboxylic acids to form acyl azide intermediates, and then react with alcohols or amines to form N-substituted carbamates or amides.
Some carboxylic acids that cannot prepare N-substituted carbamates through the Schmidt reaction can use the characteristics of DPPA to achieve their goals; and the amide-forming reaction of DPPA makes it occupy a place as a condensation agent in polypeptide synthesis. .
Reaction of DPPA and active alcohol to prepare azide
Using DPPA through the Mitsunobu reaction to replace the hydroxyl group to synthesize azide, but the Mitsunobu reaction will generate a large amount of by-products and is difficult to purify.
The following introduces a method to obtain the same product. Using DPPA and DBU, the hydroxyl group can be replaced to obtain an azide with a configuration flipped. This reaction produces by-products diphenyl phosphate and DBU salt, which can be washed away with water. Great for avoiding elimination products. However, this reaction only works well for active alcohols (benzyl alcohol or the α-hydroxyl group of carboxylic acid).
Reaction mechanism
Under DBU alkaline conditions, alcohol reacts with DPPA to obtain phosphate ester. The substituted DBU azide salt reacts with SN2 on the phosphate ester, and the configuration is reversed.
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 4020assay was 87%.HPLC conditions [ CH3CN:H20 gradient ion 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.
