Azidotris(dimethylamino)phosphonium hexafluorophosphate can be used as a coupling reagent for amide and peptide synthesis via acyl azides; it can undergo Curtius rearrangement in the absence of nucleophiles to give the corresponding isocyanates; it can be used to give iminophosphonates by irradiation; and it can be used as a diazo transfer reagent.
Bromine (1 equiv) is added dropwise to Hexamethylphosphorous Triamide (1 equiv) in dry diethyl ether. After the addition is complete, Potassium Hexafluorophosphate (1 equiv), dissolved in H2O is added, and the solid formed is filtered and washed with H2O. After drying under vacuum, the solid is dissolved in acetone and Sodium Azide (1.5 equiv) is added. The mixture is stirred overnight at 25 °C, then the sodium bromide formed and the excess of sodium azide is filtered off and the solvent is removed under vacuum.
Azidotris(dimethylamino)phosphonium hexafluorophosphate is very stable, not hygroscopic, and can be stored indefinitely under
vacuum. The related bromine derivative is an exceptionally safe azide, that does not detonate by shock, friction, rapid heating, or even flame. When used in combination with carboxylic acids, the potential
carcinogenic Hexamethylphosphoric Triamide is a side-product and the reagent must be handled with caution.
