Solvent-Promoted Oxidation of Aromatic Alcohols/Aldehydes to Carboxylic Acids by a Laccase-TEMPO System: Efficient Access to 2,5-Furandicarboxylic Acid and 5-Methyl-2-Pyrazinecarboxylic Acid

Laccase coupled with 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) is a wellknown catalytic system for the oxidation of alcohols to the carbonyl compounds. In this work, a simple yet effective solvent engineering strategy is developed to enable aromatic alcohols/aldehydes to be efficiently oxidized to carboxylic acids by a laccase-TEMPO system. Citrate buffer (100-300 mm, pH 6) rather than the widely used acetate buffer (pH 4-5) proves to be optimal for this purpose. The roles of citrate are discussed in laccase-TEMPO-catalyzed synthesis of carboxylic acids. 5-Hydroxymethylfurfural (HMF) of 200 mm is oxidized to 2,5-furandicarboxylic acid (FDCA), a top-value biobased chemical in the polymer industry, in 28 h with a yield of up to 97%. Of the 18 substrates examined, 11 alcohols are converted to target carboxylic acids with >90% yields by this method, with 2 alcohols giving >60% yields of carboxylic acids. Gram-scale preparation of FDCA and 5-methyl-2-pyrazinecarboxylic acid, an important drug intermediate, is demonstrated with total turnover numbers up to 110 000 for laccase and space-time yields up to 1.0 g/(L.h). This chemoenzymatic approach may be a promising alternative to traditional chemical oxidations for the synthesis of carboxylic acids.

Automated summary

A simple yet effective solvent engineering strategy has been developed to enable aromatic alcohols/aldehydes to be efficiently oxidized to carboxylic acids by a laccase-TEMPO system. Citrate buffer is found to be optimal for this purpose. This chemoenzymatic approach shows promise as an alternative to traditional chemical oxidations for the synthesis of carboxylic acids.