Science of Synthesis

Zhu, H.; Fan, Q., Science of Synthesis Knowledge Updates, (2024) 3, 370.

Dichloromethyl methyl ether is a robust reagent for the formylation of aromatics in the presence of Lewis acids. Formerly, the only known preparations of dichloromethyl methyl ether were performed from methyl formate using highly toxic phosphorus pentachloride or triphenylphosphine oxide/phosgene. The above reactions are also difficult to handle in an industrial setting. Recently, alkyl dichloromethyl ethers ‌2‌ have been obtained through dropwise addition of oxalyl chloride to a mixture of alkyl formate ‌1‌ and N-methyl-N-phenylformamide (N-methylformanilide) at 25–60 °C until generation of gas stopped (‌Scheme 1‌).[‌3‌,‌4‌] This protocol has the advantages of simple operation, which is applicable to large-scale synthesis.

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