C‐Acylation of Guaiacol with Acetic Acid Over Solid Acid Catalysts Under Mild Reaction Conditions

Abstract The direct acylation of substituted arenes by carboxylic acids offers a sustainable route to valorize biomass‐derived aromatics, avoiding the use of more hazardous and high‐impact reagents such as anhydrides or acyl chlorides. In this work, we study the liquid phase acylation of guaiacol (G) with acetic acid (AA) at 120 °C and atmospheric pressure, catalyzed by commercial Aquivion PW87 resin. This system yields 2‐metoxyphenyl acetate (MPA) and 4‐hydroxy‐3‐methoxyacetophenone (p‐HMAP), valuable intermediates to produce fine chemicals. MPA is the primary kinetic product, but it is progressively consumed with simultaneous formation of HMAPs and G, indicating a sequential reaction pathway that favors the formation of p‐HMAP with high regioselectivity (para/ortho‐HMAP molar ratio of 26). Interestingly, from the mechanistic viewpoint and given the similar energetics of the two isomers, this finding can only be rationalized by invoking an intermolecular mechanism, rather than an intramolecular (or Fries) rearrangement. Electronic structure calculations were used to investigate pathways involving either MPA reacting with G to form HMAPs, or two MPAs yielding G and O‐acylated acetophenones (minor products). The results suggest that the latter governs the acylation regioselectivity, with the key step being the acid‐activated attack of the MPA ester on an aromatic ring, energetically favoring p‐HMAP formation.