Microwave-assisted synthesis of substituted fluorophenyl mono- and diazides by SNAr. A fast methodology to prepare photoaffinity labeling and crosslinking reagents

•Microwave-assisted synthesis of substituted fluorophenyl mono- and diazides by SNAr.•There is synergic effect between the type of substituent and amount of sodium azide.•Product distribution and mechanism is explained in terms of a free-energy diagram.

The reaction of sodium azide with perfluorobenzene, containing an electron-withdrawing group, under microwave irradiation results in the fast preparation of p-substituted tetrafluorophenyl monoazides. Having an excess of sodium azide and a strong electron-withdrawing group like NO2 or CN, fluorophenyl diazides are also produced upon conventional or microwave heating. A synergic effect between the amount of sodium azide and the electron-withdrawing character of the substituents is observed giving different products. A discussion on the products and reaction mechanism is presented.

Graphical abstractThe reaction of sodium azide with perfluorobenzene, containing an electron-withdrawing group, under conventional heating and microwave irradiation was investigated. A synergic effect between the amount of sodium azide and the electron-withdrawing character of the substituents is observed giving different products. A discussion on the products and reaction mechanism is presented.Figure optionsDownload full-size imageDownload as PowerPoint slide