Friedel-Crafts hydroxyalkylation via high hydrostatic pressure in solvent and catalyst-free conditions

Abstract: Within the constantly evolving fields of green chemistry, the use of nontraditional activation methods takes a central role. Their contribution works by relieving the necessity of harsher chemicals or conditions to initiate certain organic reactions. Friedel-Crafts alkylation/hydroxyalkylation is an electrophilic aromatic substitution that is one of the most important methods to create C−C bonds. It is instrumental in pharmaceutical, fine chemical and material chemistry industries, commonly relying on Lewis acid catalysts to be activated, generally aluminum chloride. In this work, hydroxyalkylation has been performed between various substituted pyrroles and trifluoroacetophenones under high hydrostatic pressure (HHP) without the use of solvent or catalyst. In the optimized HHP reactions, yields up to 96% were obtained under 3.8 kbar of pressure compared to 5% yields observed at ambient pressure. High hydrostatic pressure has shown to be an effective and green activation method for this reaction by removing the need for addition of the catalyst and its subsequent removal from the product mixture, as well as negating the need for solvent.