Coupling solid acid resin with PVA membrane for intensifying citalopram synthesis by in situ water separation

Citalopram is a widely employed antidepressant and commonly produced by intramolecular etherification of 5-cyanodiol with highly corrosive and toxic p -toluenesulfonyl chloride as co-reactant. In this work, citalopram was synthesized using a catalyst-membrane coupling reactor (CMCR) in the absence of p -toluenesulfonyl chloride. The CMCR comprised a solid acid resin catalyst (HND-2) and a polyvinyl alcohol (PVA) membrane supported on a polymeric hollow fiber to achieve in-situ water separation through vapor permeation. The results revealed that incorporating the PVA membrane increased the conversion of 5-cyanodiol hydrochloride and selectivity towards citalopram by approximately 9.2 % and 4.0 %, respectively. It was found that water adsorbed and confined on HND-2 catalyst created micro-environment for the dissociation of hydrogen ions and etherification reaction. The Karl Fischer titration revealed that vapor permeation by PVA membrane effectively and completely removed the generated water during the reaction, resulting in an improvement in catalytic performance. The PVA membrane also maintained its separation capacity in six reaction cycles, demonstrating a good reusability in CMCR for the etherification of 5-cyanodiol hydrochloride.