Kinetic Study of the Hydrogenation of 2-(6-Methoxy-2-naphthyl)propenoic Acid to (S)-Naproxen with Ruthenium BINAP Catalyst in Methanol

Abstract

The understanding of efficient chiral syntheses is important in the development of the pharmaceutical industry. The discovery and subsequent investigations of the RuBINAP catalyst for the simple synthesis of the nonsteroidal antiinflammatory drug (NSAID) naproxen is an example of a practical application of chiral synthesis, although there is little published information on the reaction kinetics. The aim of this study was to provide kinetic and enantioselectivity data and the Arrhenius parameters for kinetics over a range of temperatures and H2 pressures under H2 mass-transfer-free conditions. An additional aim was to investigate the effect of TEA on the reaction rate, which has not been investigated previously for this substrate. The study is innovative in that it uses in situ UV−vis spectroscopy to investigate the reaction kinetics, providing some significant advantages over intrusive sampling techniques. The study confirmed available literature values and demonstrated that, under a substrate/TEA ratio of 1, the maximum H2 pressure required at 25 °C was only 30 bar to achieve a maximum reaction rate and enantioselectivity. TEA was shown to significantly retard the reaction rate, indicating that there is an optimum TEA/H2 ratio in rate and enantioselectivity.