Direct Oxidation Of Primary Aryl Alcohols To Carboxylic Acids Catalyzed By Laccase-mediator System

Carboxylic acids are an important type of chemicals,and are widely used in the fields of fine chemicals,pharmacueticals,and polymers.The oxidation of primary alcohols to carboxylic acids is one of the pivotal reactions in organic chemistry.Stoichiometric strong oxidant-and metal-based chemical methods remain predominant in the synthesis of carboxylic acids from primary alcohols,which suffer from environmental unfriendliness.O2-dependent biocatalytic oxidations have many advantages such as mild reaction conditions,environmental friendliness,and high selectivity,thus attracting increasing interest.Multi-enzyme cascade oxidation systems are efficient,whereas they are complex,and the compatibility between the optimal conditions of the enzymes is critical.The cascade oxidation by a single enzyme is performed in a simple manner,but the enzymes capable of efficiently oxidizing the hydroxyl group as well as the formyl group are rare.Therefore,the oxidation of the primary alcholols to carboxylic acids via a single enzyme remains challenging.2,2,6,6-Tetramethylpiperidine-l-oxyl(TEMPO)is a well-known organocatalyst capable of oxidizing the hydroxyl group;TEMPO coupled with laccase enables efficient oxidation of alcohols with O2 as the oxidant,which does not require cofactors.Recently,we found that buffer had a significant effect on the promiscuous activity of laccase-TEMPO toward the aldehyde oxidation.In this thesis,with the oxidation of 5-hydroxymethylfurfural(HMF)to 2,5-furandicarboxylic acid(FDCA)as the model reaction,the effects of various parameters on laccase-TEMPO-catalyzed FDCA synthesis were investigated.Based on the study on the rate-limiting step,the preliminary mechanism insight into the effect of buffer on the FDCA synthesis was provided.Then,the oxidation of hydrophobic benzyl alcohol by laccase-mediator systems was studied in organic solvent/buffer biphasic system.The major results were summarized as follows.1.Among the parameters tested,buffer salt and pH exerted the most significant effect on the FDCA synthesis catalyzed by laccase-TEMPO.In the optimal buffer(citrate buffer,300 mM,pH 6.0),laccase-TEMPO-mediated HMF oxidation was conducted,affording FDCA with the yields of>80%after 24 h,which are much higher than those obtained in acetate buffer(50-300 mM,pH 4.5-5).We found that laccase-TEMPO displayed good promiscuous activities toward aldehyde based on the study on the rate-limiting step(the oxidation of 5-formyl-2-furancarboxylic acid(FFCA)to FDCA.So,FFCA could be quickly oxidized to FDCA.Laccase-TEMPO system was capable of efficiently oxidizing 200 mM HMF to FDCA within 26 h when pH 6.0 was kept,with a yield of 95%.When the reaction was scaled up to 50 mL,189 mM of FDCA was produced within 30 h,thus providing a space-time yield up to 1.0 g/L h.Upon purification,FDCA was obtained with an isolated yield of 90%and the purity of 95%.The substrate scope was studied,and hydrophilic primary aryl alcohols were readily oxidized to carboxylic acids,with the yields up to>99%.Finnally,the scale-up synthesis of 5-methylpyrazine-2-carboxylic acid(MPCA),a commercially interesting intermediate,was conducted,followed by purification.MPCA was isolated with a yield of 92%.2.The addition of the co-solvent dimethyl sulfoxide(DMSO)resulted in the enhanced solubility of hydrophobic benzyl alcohol in H2O,but also readily decreased its conversions.As compared to TEMPO,other active mediators did not provide the improved results in the synthesis of benzoic acid.The laccase-compatible organic solvents with proper partition coefficients toward substrate and product included butyl acetate,methyl tert-butyl ether,and cyclopentyl methyl ether.In butyl acetate/citrate buffer biphasic system,the highest conversion(18%)was obtained in laccase-TEMPO-catalzed benzyl alcohol.Interestingly,the selectivity toward benzaldehyde was more than 99%in biphasic system,since the synthesis of benzoic acid was significantly inhibited.The addition of phase transfer catalysts tested could not effectively promote the oxidation of benzyl alcohol.In this study,the application scope of laccase-TEMPO was expanded in synthetic chemistry.An efficient laccase-TEMPO-catalyzed system was successfully constructed for the direct oxidation of hydrophilic primary aryl alcohols to carboxylic acids in this study.The mechanism of the buffer effect on the FDCA synthesis was preliminarily unvealed.It may not only enrich the theoretical knowledge of this catalytic oxidation system,but also lay the technical foundation for the large-scale preparation of aryl carboxylic acids.