Science of Synthesis

Zhu, H.; Fan, Q., Science of Synthesis Knowledge Updates, (2024) 3, 369.

Although the chlorination of ethers is often achieved using chlorine gas as the chlorinating agent under either thermal or photochemical conditions, some reactions undergo exhaustive chlorination under ultraviolet irradiation to provide the corresponding fully halogenated derivatives. In this protocol, a specially constructed ultraviolet light source is required to promote chlorination, which significantly limits its application in the chemical industry.[‌2‌] Recently, a combination of oxalyl chloride and N-methyl-N-phenylformamide has found application in the dichloromethylation of formates (see ‌Scheme 1‌).[‌3‌,‌4‌] Except for this, chlorination with phosphorus pentachloride followed by chlorine–fluorine exchange of formates affords difluoromethyl ethers in moderate to good yields at room temperature (see ‌Scheme 2‌).[‌5‌] The chlorine–fluorine exchange process is carried out using triethylamine trihydrofluoride (Et3N•3HF) as the exchange medium.

References