A Mild Heteroatom (O-, N-, and S-) Methylation Protocol Using Trimethyl Phosphate (TMP)–Ca(OH)₂Combination

Abstract

A mild heteroatom methylation protocol using trimethyl phosphate (TMP)–Ca(OH)₂ combination has been developed, which proceeds in DMF, or water, or under neat conditions, at 80 °C or at room temperature. A series of O-, N-, and S-nucleophiles, including phenols, sulfonamides, N-heterocycles, such as 9H-carbazole, indole derivatives, and 1,8-naphthalimide, and aryl/alkyl thiols, are suitable substrates for this protocol. The high efficiency, operational simplicity, scalability, cost-efficiency, and environmentally friendly nature of this protocol make it an attractive alternative to the conventional base-promoted heteroatom methylation procedures.

Key words

trimethyl phosphate - calcium hydroxide - heteroatom methylation - aqueous S-methylation - N-sulfonamide methylation

Publication History

Received: 16 December 2021

Accepted after revision: 04 January 2022

Accepted Manuscript online:
04 January 2022

Article published online:
03 March 2022

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