ABSTRACT
Azides are an important group of compounds in synthetic chemistry and chemical biology. Azides are sterically less demanding and have greater solubility compared to carbamates and amides. 1 Uses of azides include photoaffinity labeling of biomolecules. They are precursors in the “click chemistry” reactions to form linkages for various conjugates and bioorthogonal chemical reporters. 2 Azides can be prepared from amines via the diazotransfer reaction with triflyl azide (TfN3) 1,3,4 at mild reaction conditions and in good yield with complete retention of configuration. The drawback of the protocol is that a three-component solvent system of H2O/MeOH/CH2Cl2 (v/v/v =3:10:3) and a large excess of reagent (TfN3) must be used. This complicated solvent system was developed by Wong’s group from the earlier method, in which Tf2O was directly added to a biphasic mixture of CH2Cl2 and saturated aqueous NaN3. 5 In the presence of water, Tf2O would be hydrolyzed inevitably, and therefore an excess amount of Tf2O and NaN3, both highly toxic, had to be used. Also, the formed TfN3 is dissolved in CH2Cl2, which is not a good solvent for many substrates for the subsequent diazotransfer reaction. Wong developed a homogeneous phase by carefully mixing H2O, MeOH, and CH2Cl2, 6 but a slight difference in the ratio of the solvents may still lead to a somewhat unpredictable result. In 2006, Titz and co-workers developed a solvent system of MeOH/toluene/H2O, 7 but it is not a convenient solvent for a large number of carbohydrate substrates.
