In 1968 Seyferth et al. reported [1] that the trimethylsilyl (TMS) derivative of diazomethane (TMSÀCHN2, 4),[2, 3] described by Lappert et al.[2a] reacts with acetic acid (2a) in dry benzene to generate TMS-methyl acetate (5a), Scheme 1. This reaction was proposed to arise from the protonation of 4 by 2a and then nucleophilic substitution of N2 by acetate in the resulting TMS-substituted methyl diazonium intermediate (6a! 5a).[1, 4] However, AcOTMS and methyl acetate (3a) were also generated in 40–60% yield. Seyferth et al. suggested that the intermolecular protodesilylation of intermediate 6a by the acetic acid generates a methyl diazonium intermediate [AcO][CH3N2](7a), thus yielding 3a.[1] In 1981 Aoyama, Shioiri, and co-workers reported that a simple modification of the conditions reported by Seyferth etal. involving the addition of methanol as a cosolvent (20% v/v, 4.94 m), increased the yields of methyl esters 3 to near quantitative (90–99%).[5a, b] Unlike 1, which is a gas (bp À238C) and requires prior generation from toxic and irritant N-methyl N-nitroso species, TMSÀCHN2 (4) is a stable liquid (bp 968C)[1] that is easily handled and is commercially available.

Over the last 26years, the conditions reported by Aoyama, Shioiri, and co-workers (4, 5m CH3OH in toluene or benzene)[5a] have been widely adopted as a safe and convenient alternative to the use of 1 for methyl esterification,[3] especially by analytical chemists for acid derivatization prior to chromatographic analysis.[6] Although it is known that methanol is not the methylating agent,[7] the mechanism of the reaction has not been investigated in any detail.[3b, 5a] Herein we demonstrate, by way of isotopic labeling, that the methyl esterification of carboxylic acids by 4/CH3OH proceeds through the in situ methanolytic liberation of diazomethane (1).