Reactions of two primary aromatic amines in modified supercritical carbon dioxide to synthesize sulfonamides: On-line SFC to perform solubility measurements and method to monitor reaction progress

Abstract

Aniline and phenylethylamine react with 4-nitrobenzenesulfonyl chloride in 4% acetone modified supercritical fluid carbon dioxide (SFCO2) to produce nitro-sulfonamide products via NS bond formation. Solubility measurements of reactants and products in pure SFCO2 were performed at temperatures 353 K, 363 K, 373 K with pressures ranging from 10 MPa to 20.3 MPa. Aniline exhibits good solubility in SFCO2 and unlike phenylethylamine does not form a carbamate. Estimates of free phenylethylamine release efficiency from its pre-formed carbamate in SFCO2 were obtained. Synthetic reactions were performed at 16.8 MPa with temperatures 353 K, 363 K, and 373 K. Under such conditions, on-line SFC reaction progress monitoring established phenylethylamine effectively reacted as a free base at approximately four times the rate of aniline. Nitro-sulfonamide product yields were 75–82.6% using phenylethylamine and 53.9–70.2% using aniline. Aniline product yields were lower due to by-product formation. This study involved using two different interchangeable on-line SFC interfaces.