The Mechanochemical Fries Rearrangement: Manipulating Isomer Ratios in the Synthesis of p‐Hydroxyacetophenone at Different Scales. Issue 21 (8th March 2023)

• Record Type: Journal Article
• Authors: Baier, Daniel M.; Rensch, Tilo; Bergheim, Konrad; Pietryga, Viktoria; Grätz, Sven; Borchardt, Lars
• Is Part Of: Chemistry. Volume 29:Issue 21(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-08
• Subjects: ball milling -- extrusion -- Fries rearrangement -- mechanochemistry -- para-hydroxyacetophenone; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202203931
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Herein, 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. Abstract : para ‐Hydroxyacetophenone is prepared by the first mechanochemical Fries rearrangement. The reaction was optimized in the ball mill and then transferred to a continuous process in a twin‐screw extruder. The isomer ratio can be influenced by reaction parameters such as LAG or temperature.