Chemo-enzymatic Baeyer–Villiger oxidation in the presence of Candida antarctica lipase B and ionic liquids

Abstract

A new method for the chemo-enzymatic Baeyer-Villiger oxidation of cyclic ketones to lactones has been developed. The influence of reaction parameters and the structure of various ionic liquid was studied. Free Candida Antarctica lipase B or Novozyme-435 suspended in an ionic liquid were used as the catalytic phase. The reaction was carried out under mild conditions at room temperature using 30% aq. H2O2 as the oxidation agent. 1-Butyl-3-methyl bistriflimide was the most effective ionic liquid and 10 increased the reaction rate compared to toluene. Lipase exhibited good stability, and the ionic liquid could be easily reused. Therefore, a general chemo-enzymatic method for the oxidation of cyclohexanones and cyclobutanones to obtain adequate lactones in high yields (79-95%) has been proposed. 65 enzymes in ionic liquids including polarity, hydrophobicity, nucleophilicity, hydrogen bonding ability, viscosity, enzyme dissolution, and surfactant effect. [18][19][20] In addition, the parameters that quantify the interactions of the proteins and the aqueous electrolytes, such as cosmotropicity vs. chaotropicity, have been 70 proposed for explaining protein behaviour in aqueous ionic liquids. Unfortunately, the anions of ionic liquids do not always strictly follow the Hofmeister series for protein stability. 16 Ionic liquids can also form so-called organised 'nano-structures,' which are described as hydrogen bonded polymeric supramolecules that have 75 polar and non-polar regions. The structure of the ionic liquids can protect the crucial water in the protein from solvophobic

Optimization of chemoenzymatic Baeyer–Villiger oxidation of cyclohexanone to ε‐caprolactone using response surface methodology

“…In the present work, in order to improve the stability of lipase, T. laibacchii lipase was immobilized on diatomite supports using glutaraldehyde as a crosslinker. In this study, the initial concentration of cyclohexanone was 1.22 M and the concentration of the target product ε‐CL reached about 1.2 M according to the yield of 98.06%, being much higher than that (0.225–0.37 M) with a conversion of 80–90% in the previous other studies . Among them, the highest concentration of 0.37 M was achieved when an ionic liquid was used as solvent, and the yield of caprolactone reached 98.06% because the T. laibacchii lipase used in this study was immobilized by cross‐linking technology, glutaraldehyde was used as a crosslinking agent for T. laibacchii lipase and diatomite support to improve the stability of lipase.…”

“…It was reported that the inhibition of lipase by caprolactone, water, oxygen, and EtOAc is negligible, while the substrate UHP and by‐product acetic acid have a strong inhibitory effect on lipase because they can cause lipase inactivation. Due to the presence of an acidic environment, the protein conformation of the lipase changes, the disulfide bond is broken, and the substituent in the—and/or—position of the acetic acid prevents the active site of the enzyme from binding to the substrate, resulting in significant reduction of the reaction rate.…”

“…It is generally believed that CaL B has good stability; however, the slow lipase deactivation occurred when CaL B was exposed to H 2 O 2 . The lipase was not sufficiently stable to use in the next cycle when the reaction was carried out in toluene and at higher temperatures . Lipase deactivation occurs gradually which increases with time and eventually the oxidation process results in disruption of disulfide bridges and loss of structure …”

“…The conversion of cyclohexanone to ε‐CL based on BV oxidation by the chemoenzymatic method usually involves hydrogen peroxide or urea hydrogen peroxide (UHP) as an oxidant, immobilized Candida antarctica lipase B ( CaL B) as a catalyst, ethyl acetate (EtOAc) as an acyl donor, and a solvent . The concentration range of ε‐CL formed based on the above chemoenzymatic process was about 0.225–0.37 M with conversion of 80–90% in their studies, and this concentration is relatively low and should be greatly increased in order to improve the economy of the process.…”

Recent advances in exploiting ionic liquids for biomolecules: Solubility, stability and applications

“…As discussed in Section , the use of ILs for enzymes has advantages over conventional organic solvents and water, including high conversion rates and enantioselectivity , better enzyme stability , recoverability, and recyclability . Furthermore, ILs can be used to perform biotransformations with polar or hydrophilic substrates that are insoluble or sparingly soluble in most organic solvents, such as amino acids and carbohydrates .…”