Tributylstannyl Azide as Efficient Reagent in the Synthesis of Aryl Azides from Aryl Amines

Abstract

The use of aryl azides as synthetic intermediates has attracted much attention due to their potential applications in organic and bioorganic chemistry. Because of their relatively high stability, these compounds have found biological and industrial use as photoaffinity labeling reagents for biomolecules, as cross-linkers in photoresistors, for conducting polymers, and for light-induced activation of polymer surfaces. In recent years, aryl azides have been popularized in the field of "click chemistry" due to their participation in Cu-(I)-catalyzed cycloaddition to alkynes (CuAAC). One of the most straightforward routes for the preparation of aryl azides involves diazotization of aryl amines with tert-butyl nitrite (t-BuONO), followed by addition of trimethylsilyl azide (TMSN3) under mild conditions. Although this procedure is highly efficient with excellent yields, the use of TMSN3 has some downsides; this compound is volatile and hydrolytically unstable resulting in the release of toxic and explosive hydrazoic acid. Furthermore, it has a high cost and a tedious synthetic method. On the other hand, trialkylstannyl azides, which can also act as transfer agent of N3 group, are more stable, more resistant to hydrolysis and are easily obtained by the reaction of the corresponding trialkyltin chloride with sodium azide. These properties, together with the importance of aryl azides, encouraged us to initiate a study on the reaction of aryl amines with tributylstannyl azide, using t-BuONO and p-toluenesulfonic acid for the diazotization process. We found that, under previously optimized reaction conditions, a variety of substituted aryl amines, with both electron-withdrawing and electron-donating groups were transformed into aryl azides in good to excellent yields. An important advantage of this method is that, despite their high toxicity, tin byproducts can be reconverted into the starting tributylstannyl azide by treatment with sodium azide and reused after chromatographic separation of the aryl azide.