Membrane nanoreactors for mild and high-efficiency synthesis of β-blockers

Abstract

β-blockers, such as propranolol, are widely used in the treatment of cardiovascular diseases. However, current catalytic systems for their synthesis often suffer from low efficiency, poor selectivity, and the need for harsh reaction conditions. Here, amine-functionalized graphene oxide (NGO) membrane nanoreactors were developed for the efficient synthesis of propranolol. By incorporating alkaline catalytic sites and optimizing interlayer spacing and reactant molar ratios, propranolol synthesis was achieved with directional flow, ≈100% conversion, and ≈100% selectivity in less than 4.63 s at 23°C. Density functional theory calculations revealed that adjusting the interlayer spacing of the NGO membrane promoted the reaction from thermodynamic to kinetic control through the confinement effect. The method was successfully extended to the synthesis of metoprolol, bisoprolol, pindolol, and naftopidil, demonstrating high-efficiency flow synthesis for various β-blockers. This work offers a highly efficient, environmentally friendly approach for the synthesis of β-blockers with high conversion and selectivity.