An investigation into the synthesis of azido-functionalised coumarins for application in 1,3-dipolar “click” cycloaddition reactions

A range of reported methods have been assessed for the synthesis of two coumarin fluorophores containing azides, 1a and 2, for subsequent “click” modification. In the case of 1a reported methods were successfully applied, but the resulting azide proved to be rather unstable and appears more suited to in-situ generation and conversion to the “click” triazole. In the case of 2, reported methods for the synthesis of precursor 5 were ineffective in two cases and resulted in either no bromination α-to the carbonyl or the formation of multiple unwanted side-products, some of which were isolated, 6-13. The use of CuBr2 in excess or Br2 in 50% HBr in acetic acid did result in the isolation of 5, which could be efficiently converted to 2 using excess NaN3 in THF.