Practical, mild and efficient electrophilic bromination of phenols by a new I(iii)-based reagent: the PIDA–AlBr3 system

Abstract

A practical electrophilic bromination procedure for phenols and phenol–ethers was developed under efficient and very mild reaction conditions. A broad scope of arenes was investigated, including the benzimidazole and carbazole core as well as analgesics such as naproxen and paracetamol. The new I(III)-based brominating reagent PhIOAcBr is operationally easy to prepare by mixing PIDA and AlBr₃. Our DFT calculations suggest that this is likely the brominating active species, which is prepared in situ or isolated after centrifugation. Its stability at 4 °C after preparation was confirmed over a period of one month and no significant loss of its reactivity was observed. Additionally, the gram-scale bromination of 2-naphthol proceeds with excellent yields. Even for sterically hindered substrates, a moderately good reactivity is observed.