Benzyl p-Toluenesulphonate as an 0-Benzylating Agent for the Protection of Phenols

Abstract

Benzylation is a popular method of protecting phenolic groups during synthetic procedures. Benzyl ethers are stable to basic and mildly acidic conditions, but are cleaved readily by stronger acid, reduction, or most commonly by hydrogenolysis¹. Current methods of converting phenols into O-benzyl derivatives rely principally on the use of commercially available benzyl chloride or benzyl bromide and usually involve heating a mixture of the phenol and the halide with anhydrous potassium carbonate in dry acetone or DMF¹. To increase reactivity of the halide, potassium iodide may be added to the reaction mixture to generate benzyl iodide ‘in situ’. A major disadvantage of using alkyl halides in the preparation of phenolic ethers is the amount of simultaneous C-alkylation which can occur. Whilst C-alkylation is reduced by using polar aprotic solvents¹, it may still become an important side reaction during the alkylation of phenols containing phloroglucinol substitution patterns, yields of 0-alkyl derivatives decreasing markedly, and a complicated mixture of products generally ensues. In the cases of 0-methylation or -ethylation, such unwanted side-reactions can be minimised by employing dimethyl sulphate as the alkylating agents instead of the halides. No similar agents have been available for 0-benzylation reactions.