Site Selectivity in the Synthesis of O-Methylated Hydroxamic Acids with Diazomethane

In this paper we report the results obtained by treating some selected hydroxamic acids with diazomethane in ethereal media. The multitask reagent diazomethane was used either as a base to induce deprotonation of the chosen hydroxamic acids or as conjugated acid which undergoes one-pot methylation processes of the generated anions. Product distributions clearly showed that a high site selectivity is expressed by the different deprotonated species in the alkylation processes. Under the adopted conditions, the prevalent site of methylation is in all the cases the oxygen of the hydroxamic acid. While in aliphatic hydroxamic acids only O-alkylation is observed, in the aromatic substrates, the NH group competes with the OH function as the nucleophilic site, although the OH reactivity still dominates.