High pressure initiated solvent and catalyst-free instant Paal–Knorr reactions

Abstract

High hydrostatic pressure (HHP) has been found to be a highly efficient activation method in the catalyst- and solvent-free Paal–Knorr cyclization reaction. The reactions were carried out at pressures from 1 bar (control) up to 3.8 kbar and the observed quantitative yields and seconds long reaction times indicate the usefulness of the developed methodology. In addition, the application of HHP resulted in selective formation of the desired products that can be isolated without any purification. This study is the first report on high pressure-activated small molecule reactions when a pressure shock-like behavior was observed, namely several substrates reached quantitative yields in extremely short reaction times (1–10 s). The high pressure activation strategy could also be readily scaled up to preparative levels. The application of HHP enables achieving of a truly green process, that is catalyst and solvent-free (except when NH₄OH was used), occurs in seconds at room temperature with quantitative yields thus no purification is necessary and the only byproduct is non toxic water.