A Mechanistic Survey of the Oxidation of Alcohols and Ethers with the Enzyme Laccase and Its Mediation by TEMPO

Abstract

The oxidation of alcohols and ethers by O2 with the enzyme laccase, mediated by the stable N‐oxyl radical TEMPO, affords carbonylic products. An ionic mechanism is proposed, where a nucleophilic attack of the oxygen lone‐pair of the alcohol (or ether) onto the oxoammonium form of TEMPO (generated by laccase on oxidation) takes place leading to a transient adduct. Subsequent deprotonation of this adduct α to the C−O bond leads to the carbonylic product. Additional mechanistic considerations for the laccase‐mediated oxidation of ethers and thioethers are offered. The proposed mechanism is supported by: (i) investigating the inter‐ and intramolecular selectivity of oxidation with appropriate substrates, (ii) thermochemical considerations, and (iii) attempting a Hammett correlation for the oxidation of a series of 4‐X‐substituted benzyl alcohols, wherein a shift of the rate‐determining step as a function of the 4‐X‐substituent results. Based on the above points, the lack of mediation efficiency of another stable N‐oxyl radical (viz., IND‐O·) can be explained. (© Wiley‐VCH Verlag GmbH & Co KGaA, 69451 Weinheim, Germany, 2002)

Laccase‐catalyzed mediated oxidation of benzyl alcohol: the role of TEMPO and formation of products including benzonitrile studied by nanoelectrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

“…Deprotonation of the adduct gives rise to the aldehyde and to the reduced form of TEMPO. Laccase oxidizes the reduced TEMPO to regenerate TEMPO, and further oxidation leads to the oxoammonium ion 18. This is a corresponding mechanism to those suggested for TEMPO‐mediated oxidation of alcohols with oxidation sources other than laccase 19, 20…”

“…We first describe the analysis of pure TEMPO and its redox forms in the laccase–TEMPO system. The measurements were made to determine if our system provides results comparable to those obtained earlier by theoretical and indirect methods 17, 18. We also wished to clarify the reaction mechanism, i.e.…”

Nitroxide‐Catalyzed Alcohol Oxidations in Organic Synthesis

“…69 Under certain conditions, benzylic alcohols can be oxidized with high selectivity (albeit in low yield) in the presence of primary alcohols, as the example shown in Scheme 12.5 demonstrates. 70 …”

“…192 Ether carbons are also generally stable, but again, exceptions were reported for select benzyl ethers. 70,193,194 …”

Laccase treatment of recycled blue dyed paper: physical properties and fiber charge

“…In terms of removing color from dyes pulps, redox potentials are important and the choice of mediator influences the extent of color removal [27]. TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) was selected as laccase mediator for this study of recycled blue dyed pulp, based on a previous report of laccase-TEMPO treatment increasing carbonyl products [28]. This mediator has been shown to be an oxidative agent for selective oxidation of 6-hydroxy groups of cellulose [29].…”