Overcoming a Conceptual Limitation of Industrial ε-Caprolactone Production via Chemoenzymatic Synthesis in Organic Medium.

Abstract

The multi-10.000 tons scale manufactured chemical ε-caprolactone attracts high industrial interest due to its favorable biodegradability properties. However, besides being of petrochemical origin yet, its production has a conceptual limitation that is the difficult extraction of this highly water-soluble monomer from the water phase resulting from the aqueous solution of H2O2 applied as reagent. In this contribution, we report a chemoenzymatic cascade starting from bio-based phenol, which makes use of O2 instead of H2O2 and runs in pure organic medium, thus requiring only simply decantation and distillation as work-up. In a first step, phenol is hydrogenated quantitatively to cyclohexanol under solvent-free conditions with a Ru-catalyst. After simple removal of the heterogenous catalyst, cyclohexanol is converted to ε-caprolactone in a biocatalytic double oxidation with very high yields just requiring O2 as reagent. This biocatalytic process proceeds in pure organic medium, thus avoiding tedious extraction to isolate the highly water-soluble ε-caprolactone and enabling a substantially simplified work-up by only centrifugal separation of lyophilized whole cells and solvent removal. This oxidation is accomplished using a tailor-made recombinant whole-cell catalyst containing an alcohol dehydrogenase and a cyclohexanone monooxygenase mutant.