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Publications

Journal Article Ahead of print

PubMed: 42545821 DOI: 10.1002/chem.71518

Synthesis of Aspirin at the Gas-Water Interface With Phenol and Carbon Dioxide.

Chemistry

Authors: Xiaowei Song, Jinheng Xu, Chanbasha Basheer, Richard N Zare

Affiliations

  • Department of Chemistry, Stanford University, Stanford, California, USA.
  • Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen, China.
  • Department of Chemistry and Interdisciplinary Research Center for Refining & Advanced Chemicals, King Fahd University of Petroleum and Minerals, Dhahran, Saudi Arabia.

Abstract

We present a gas-water interfacial carboxylation of phenol into salicylic acid under ambient conditions, bypassing the high temperature and pressure required by the conventional Kolbe-Schmitt reaction. Phenol-containing microdroplets were sprayed with CO 2 into a high-resolution mass spectrometer, where in situ analysis revealed a highly regioselective ortho-carboxylation pathway. To scale up the process, we transitioned from microdroplets to microbubbles, extending the gas-water contact time. Milligram-scale acetylsalicylic acid (aspirin) was synthesized from 500 mL of 10 ppm aqueous phenol solution under a CO 2 atmosphere, upon the addition of acetic anhydride. This study highlights the unique reactivity of micron-scale gas-water interfaces, whether in droplets or bubbles, as effective media for the proof-of-concept conversion of dilute aqueous phenol and CO 2 into pharmaceutically relevant products under ambient conditions.

MeSH

Microbubbles, Aspirin, Solutions, Salicylic Acid, Phenol