Synthesis of alkyl aryl ethers by catalytic Williamson ether synthesis with weak alkylation agents

摘要

For almost 70 years, there have been attempts to advance the Williamson ether synthesis process to allow the use of low-cost, noncarcinogenic, weak alkylating agents and avoid salt production. These attempts to produce a "green" version of Williamson ether synthesis have been based on the use of weak alkylating agents such as carboxylic acid esters at relatively high temperatures (approximately 200 degrees C) and pressures. However, none of the processes considered was suitable for industrial application because of the high concentration of the alkali metal carboxylates required. By increasing the temperature to above 300 degrees C, it has now proved possible to carry out Williamson ether synthesis as a homogeneous catalytic process. The large temperature increase significantly boosts the alkylating power of weak alkylating agents such as alcohols, carboxylic acid esters, and ethers derived from weak Bronsted acids, which are only weak alkylating agents at room temperature. At such temperatures, carboxylic acid esters such as benzoic acid methyl ester or acetic acid methyl ester demonstrate the alkylating power usually expected of alkylating agents derived from strong acids. In the catalytic cycle of this new process, for example, the low-cost alcohol methanol and phenol were converted into anisole and water at 320 degrees C via the intermediate methyl benzoate in the presence of catalytic quantities of alkali metal benzoate and phenolate. The catalytic Williamson ether synthesis (CWES) at high temperatures is especially well-suited for the production of alkyl aryl ethers such as anisole, neroline, and 4-methyl anisole which are of industrial importance. Selectivity values of up to 99% have been reached.