Intensified Continuous Flow Synthesis of Oxazolidones

Abstract

Cyclic urethane compounds, known as oxazolidones (Oxas), have historically been synthesized using toxic, phosgene-based isocyanates, prompting the pursuit for greener alternatives. However, those alternatives face obstacles like the use of hazardous reagents and reliance on metal catalysts, leading to scalability limitations. Flow chemistry provides an effective solution, enabling safer, more efficient, and continuous production of Oxas, with enhanced catalyst recovery, reduced reaction times, and greater control over reaction conditions. Leveraging these advancements, a novel flow-based method using the aminolysis of CO₂-derived α-alkylidene cyclic carbonates (αCCs) was developed, achieving yields of about 99% for aliphatic amines in just 1–5 min, with a very high selectivity for Oxas over hydrolysis and uncyclized byproducts. This process was further optimized to synthesize oxazolidones in under 1 min, without solvents and with minimal side reactions. Furthermore, a process utilizing supported catalysts was developed, further improving catalyst recovery and overall reaction efficiency.