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

Abstract

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.

Recent Advances in the Chemical Fixation of Carbon Dioxide: A Green Route to Carbonylated Heterocycle Synthesis

“…Finally the isocyanate is intramolecularly attacked by the amino group to cyclize (Scheme 32). During the experiments for the synthesis of N-alkylated heterocycles in a continuous flow reactor on a bed of γ-Al 2 O 3 in supercritical CO 2 , authors found that under particular reaction conditions diethanolamine (1 M, at 250 • C, 15.0 MPa, and 0.2 mL/min) afforded 3-(2-hydroxyethyl)oxazolidin-2-one with a 56% of conversion and 73% selectivity [202]. At lower pressure and flow rate the oxazolidinone is converted in the expected 2,2 -(piperazine-1,4-diyl)diethanol.…”

Recent Advances in the Catalytic Synthesis of Imidazolidin-2-ones and Benzimidazolidin-2-ones

“…KOH/PEG 1000 was found to act as an efficient and recyclable catalyst (10 mol% with respect to the substrate) for the conversion of ethylenediamine, propane-1,2-diamine, and cyclohexane-1,2-diamine into the corresponding cyclic ureas. More recently, γ-Al 2 O 3 was reported to catalyze the formation of 1-(2-hydroxyethyl)imidazolidin-2-one from 2-[(2-aminoethyl)amino]ethan-1-ol, at 250 • C in supercritical CO 2 (Scheme 15) [89].…”

“…Ceria-based materials are also useful heterogeneous catalysts for the conversion of aliphatic 1,2diamines into imidazolidin-2-ones with CO2. In particular, nanoparticulate CeO2 (obtained by templating with alginate biopolymer) proved to be active for the conversion of ethylenediamine, N-(2-aminoethyl)ethane-1,2-diamine, N,N′-dimethylethane-1,2-diamine, and N- [2-(methylamino)ethyl]acetamide into the corresponding cyclic ureas, even though in low to modest yields (9-37%) [89]. On the other hand, pure ceria turned out to be a useful recyclable heterogeneous catalyst for the carbonylation with CO2 of a variety of aliphatic 1,2-diamines, in isopropanol as the solvent at 160 °C and under a relatively low CO2 pressure (five atm) (Scheme 16) [90].…”

Antibiotics from Carbon Dioxide: Sustainable Pathways to Pharmaceutically Relevant Cyclic Carbamates

“…Additionally, a Lewis acid cocatalyst is sometimes employed to activate the carbonyl group, as shown in Schemeà. Examples of catalysts include ceria, alumina, fluoride, Cs 2 CO 3 ,, and various Sn species …”