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5.3.1 Methylation

Diazomethane methylates acidic hydroxyl groups, carboxylic acids, sulfonic acids, phenols and enols. Conditions are mild and the products are obtained in high yield (Scheme 5).

Scheme 5

Mechanism

Diazomethane is a powerful methylating agent, particularly useful for mild preparation of methyl esters of acids (Scheme 6).

Scheme 6

The reactions aliphatic alcohols require catalyst because of the low acidity of the hydroxyl hydrogen. AlCl₃ and BF₃·OEt₂ are generally employed for this purpose (Scheme 7).

Scheme 7

Similarly, the reactions of aliphatic amines with diazomethane are also effective in the presence of catalysts such as BF₃·OEt₂ and cuprous cyanide. However, the methylation of aromatic amines can be accomplished without the Lewis acid catalyst.

Example:

M. L. Di Gioia, A. Leggio, A. Le Pera, A. Liguori, A. Napoli, C. Siciliano, G. Sindona, J. Org. Chem . 2003 , 68 , 7416.