The Mechanochemical Fries Rearrangement: Manipulating Isomer Ratios in the Synthesis of p‐Hydroxyacetophenone at Different Scales**

Abstract

AbstractHerein, the first mechanochemical Fries rearrangement for the industrially important synthesis of para‐hydroxyacetophenone, inside a ball mill and a twin‐screw extruder, is presented. Our approach leads to a yield of 62 % in as little as 90 minutes while liquid‐assisted grinding can shift the isomer ratio resulting in an excess of the desired para‐product. The multigram scale‐up by extrusion leads to 61 % yield in only three minutes while completely avoiding solvents. The extrusion temperature can even further be reduced by combining extrusion with a subsequent ageing step.