Efficient One-pot Synthesis of Dendritic Benzyl Azides from Their Alcohols

Abstract

Dendrimers are prepared by repetition of a given set of reactions using either divergent or convergent strategies. The two most widely studied dendrimer families are the Frechettype polyether and the Tomalia-type PAMAM dendrimers. The convergent approach to dendrimer synthesis introduced by Frechet and co-workers revolutionized the synthetic approaches to monodisperse dendrimers. An effective convergent synthesis requires a monomer that can undergo the activation and coupling steps in high yield. In addition, the coupling step must be very efficient to enable complete reaction. In this viewpoint, the dendritic benzylic azides are key intermediates in synthesis of the Frechet-type poly(aryl ether) dendrimers via click chemistry. In continuation with our research for the synthesis of dendrimers using click chemistry between an azide and an alkyne, there is still a demand to develop a simple, convenient, and efficient method to synthesize various dendritic benzyl azides. Here, we present a successful rapid synthesis of dendritic benzyl azides from dendritic benzyl alcohols via mesylation using methanesulfonyl chloride/Et3N and followed by in situ azidation (Scheme 1). In our method, each dendritic benzyl azide can be prepared in one pot: no isolation of intermediate mesylated dendrons is required. The key steps in the syntheses of dendritic benzyl azides were the mesylation of the hydroxymethyl group followed by the azidation with sodium azide. Furthermore, the purification of every dendritic molecule requires only solvent extraction.