Selectivity engineering of 2,6-diisopropylphenol in isopropylation of phenol over Cs_2.5H_0.5PW₁₂O₄₀/K-10 clay

Abstract

Propofol (2,6-diisopropylphenol), a very important drug, is typically synthesized by the isopropylation of phenol over an acid catalyst. This process consists of two series reactions, namely, the formation of 2-isopropylphenol and its further isopropylation to 2,6- and 2,4-diisopropylphenols. The selectivity to 2,6-diisopropylphenol depends on a number of parameters, and the alkylating agent, type of catalyst, and temperature play a major role. With 2-propanol (IPA) as the alkylating agent, its dehydration to propylene and the subsequent formation of isopropyl ether (DIPE) need to be considered. The fact that isopropyl ether, formed in situ, is itself a good alkylating agent further complicates the reaction network. Modeling this intricate system requires extensive experimental data free from mass-transfer limitations. Thus, the alkylation of both phenol and monoisopropylphenol was studied in the liquid phase in an autoclave at 200 °C using IPA and DIPE independently as alkylating agents, over 20% (w/w) Cs_2.5H_0.5PW₁₂O₄₀/K-10 catalyst, which is a synergistic combination of cesium-modified heteropolyacid and clay. This catalyst is better than zeolites reported in the literature. The effect of various operating parameters and catalyst reusability was also investigated. Mathematical models were proposed to probe into the intricate reaction kinetics and mechanism consistent with the experimental results.