Selective control for the laccase-catalyzed synthesis of dimers from 2,6-dimethoxyphenol: Optimization of 3,3’,5,5’-tetramethoxy-biphenyl-4,4’-diol synthesis using factorial design, and evaluation of its antioxidant action in biodiesel

[Display omitted] •Botryosphaeria rhodina MAMB-05 laccase catalyzed synthesis of 3 dimers from 2,6-dimethoxyphenol at different pH and reaction times.•Dimers were formed by oxidative coupling via CC (I, II) and CO (III) bonds.•Dimer III was synthesized from 2,6-dimethoxyphenol at pH 3.0 and at 96 h.•Synthesis of laccase-catalyzed TMBP (dimer II) at pH 6.5 was optimized by design matrix.•TMBP was applied as an antioxidant in biodiesel and its efficacy compared to BHT. The synthesis of transformed products from 2,6-dimethoxyphenol (2,6-DMP) can be selectively obtained through controlled oxidative coupling in laccase-catalyzed reactions, and the products formed are dependent upon the enzyme source, as well as, upon the reactions conditions applied. The laccase from Botryosphaeria rhodina MAMB-05 was investigated for its ability to catalyze the oxidative transformation of 2,6-DMP. Studies conducted in aqueous medium at pH 3.0 and 6.5, for reaction times of 48, 96 and 144 h, led to the formation of three dimers (I, II, III) via carbon-carbon and carbon-oxygen coupling reactions depending upon the pH and reaction time. Dimer I was identified as 3,3′,5,5′-tetramethoxydiphenylquinone by 13C NMR, while dimer II was identified by 1H NMR as 3,3′,5,5′-tetramethoxybiphenyl-4,4′-diol (TMBP). Dimer III was synthesized at pH 3.0 and was influenced by the reaction time (96h), and is predicted to be formed via carbon-oxygen coupling. The chemical structure of III (4-(2,6-dimethoxy-phenoxy)-2,6-dimethoxyphenol) was identified by ESI-Q-TOF HRMS. TMBP (II) was the only product obtained at pH 6.5 independent of the reaction times. TMBP synthesis at pH 6.5 was optimized by design-matrix using a three-factor Box-Behnken incomplete factorial-design that defined the parameters: 2,6-DMP concentration (2.6–3.4 mmol) laccase activity (1.35–3.38 U) and reaction time (120 h) to give a yield of 11.93 ± 0.49%, which agreed with the mathematical model value of 12%. TMBP was evaluated as an antioxidant to stabilize biodiesel, and showed an efficacy similar to the commercial antioxidant standard, butyl hydroxytoluene, indicating that TMBP could serve as an alternative antioxidant to stabilize biodiesel.