Continuous-/Micro-Flow Reactions Using Highly Electrophilic PCl3 and POCl3

PCl3 and POCl3 are the most important sources of phosphorus-containing compounds. They are also used for large-scale industrial productions. However, chemical reactions using the highly reactive PCl3 and POCl3 tend to result in overreactions. In addition, the reactions are usually exothermic and therefore their utilization sometimes involves significant risk. That is why some phosphorylating reagents with mild electrophilicity such as phosphoramidites have been developed. Although these mild electrophiles are very useful for the highly selective synthesis of organophosphorus compounds, problems persist: the high cost of the reagents, the generation of large amounts of waste, and the requirement of long reaction times and high temperatures. Continuous-flow technology is one of the most promising solutions for these problems. In particular, precise control of reaction times and temperatures enabled by micro-flow technology suppresses undesired reactions and allows the safe operation of exothermic reactions using highly reactive PCl3 and POCl3. This Review describes recently reported reactions of PCl3 and POCl3 using continuous- and micro-flow technologies.

Automated summary

PCl3 and POCl3 are important sources of phosphorus-containing compounds and have wide industrial applications. However, their high reactivity often leads to overreactions and poses significant risks. Phosphoramidites have been developed as phosphorylating reagents with mild electrophilicity, but they suffer from high costs, generation of waste, and long reaction times. Continuous-flow technology, particularly micro-flow technology, offers a promising solution by enabling precise control of reaction conditions and allowing safe operation with PCl3 and POCl3.