Continuous N-alkylation reactions of amino alcohols using γ-Al(2)O(3) and supercritical CO(2): unexpected formation of cyclic ureas and urethanes by reaction with CO(2)

The use of γ-Al(2)O(3) as a heterogeneous catalyst in scCO(2) 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 scCO(2) was shown to be beneficial, as higher yields were obtained in the presence of CO(2) than in its absence. A surprising discovery is that, in addition to cyclic amines, cyclic ureas and urethanes could be synthesised by incorporation of CO(2) from the supercritical solvent into the product.