Facile synthesis of symmetrical bis(benzhydryl)ethers using p-toluenesulfonyl chloride under solvent-free conditions.

Background: The benzhydryl ether moiety is widely distributed in nature and constitutes a key structural motif in numerous molecules of significant biological potential and of prospective clinical uses. Solvent-free and cost-effective facile synthesis of symmetrical bis(benzhydryl)ethers is, thus, much desirable.

Results: A simple and efficient method for the facile synthesis of symmetrical bis(benzhydryl)ethers directly from the corresponding benzhydrols has been developed using a catalytic amount of p-toluenesulfonyl chloride (5 mol%) at an oil bath temperature of 110°C under solvent-free conditions.

Conclusions: Operational simplicity, low reagent loading, high product yields, short reaction time, and solvent-free conditions are the notable advantages of the present method.