Kinetic study of the microflow synthesis of 4-hydroxyquinoline in supercritical ethanol

•Supercritical ethanol was used as a green solvent for the thermal cyclization.•The reaction mechanism and the kinetics were studied with a microreactor.•The reaction completed in 27 s at 350 °C giving 4-hydroxyquinoline in 97% GC yield.•The overall kinetics was described by a pseudo-first-order rate constant.•The corresponding activation energy was determined to be 204 ± 2 kJ mol−1.

Supercritical ethanol was used as a solvent for the thermal cyclization of ethyl 3-(phenylimino)-butanoate to 2-methyl-4-hydroxyquinoline; the reaction is of great importance in pharmaceutical and color industries but conventionally needs specific solvents with high boiling points. The mechanism and the kinetics were studied with a microreactor by measuring the yield of the product at various temperatures up to 350 °C. The reaction in ethanol completed in 27 s at 350 °C and 10.0 MPa giving the quinoline in 97% GC yield, although it required higher temperature than that in acetonitrile. The results were explained by the mechanism consisting of the two steps: (i) a reversible elimination of ethanol from the reactant yielding ketene intermediate followed by (ii) an irreversible ring closure into the quinoline. On the basis of the reaction mechanism, the rate constant and the activation energy were determined from the yield-time profiles measured at temperatures of 300–350 °C and a constant ethanol density of 0.11 g cm−3. The kinetic analysis revealed that the overall reaction is controlled by a pseudo-first-order rate constant. The activation energy was determined to be 204 ± 2 kJ mol−1, which was close to that calculated by density functional theory (187 kJ mol−1).

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