Continuous N-alkylation reactions of amino alcohols using γ-Al2O3 and supercritical CO₂: Unexpected formation of cyclic ureas and urethanes by reaction with CO₂

The use of γ-Al2O3 as a heterogeneous catalyst in scCO₂ has been successfully applied to the amination of alcohols for the synthesis of N-alkylated heterocycles. The optimal reaction conditions (temperature and substrate flow rate) were determined using an automated self-optimising reactor, resulting in moderate to high yields of the target products. Carrying out the reaction in scCO₂ was shown to be beneficial, as higher yields were obtained in the presence of CO₂ than in its absence. A surprising discovery is that, in addition to cyclic amines, cyclic ureas and urethanes could be synthesised by incorporation of CO₂ from the supercritical solvent into the product.