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

Abstract

AbstractA 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.