Abstract

The enzymatic esterification of 5-hydroxymethylfurfural (HMF) with long-chain fatty acids offers a sustainable route for producing biolubricants and other high-value chemicals. This work evaluates the synthesis of 5-hidroxymethylfurfural stearate catalyzed by immobilized lipases in both batch and continuous packed-bed bioreactors, combining molecular dynamics (MD) simulations with experimental validation to identify suitable green solvents. Four solvents were tested: 2-methyl-3-buten-2-ol (2-MB), tert-butanol (TB), 2-methyltetrahydrofuran (2-MeTHF), and cyclopentyl methyl ether (CPME). MD simulations revealed that CPME increased hydrophobic surface exposure and flexibility near the catalytic site, favoring substrate accessibility. In preliminary experimental tests, CPME provided the highest conversion (50%). In batch bioreactor at 40 degrees C, 30 mM HMF and 250 mM stearic acid achieved 67% conversion with Candida antarctica lipase B (CALB), maintaining full activity (100%) over four reuse cycles. In continuous operation, using a single packed-bed bioreactor at 0.02 mL min(-)& sup1; yielded conversions above 50% (residence time approximate to 55 min), while connecting two packed-bed bioreactors in series increased conversion to over 90% and productivity to 0.094 h(-)& sup1;, compared with 0.076 h(-)& sup1; for one column and 0.003 h(-)& sup1; in batch mode. Deviations from ideal plug flow were observed over time, attributed to substrate or product deposition and in-situ water formation shifting the reaction equilibrium. Overall, CPME proved to be an efficient and sustainable solvent for the enzymatic synthesis of 5-hydroxymethylfurfural stearate, demonstrating the feasibility of continuous operation and highlighting pathways for further optimization through improved immobilization or reactor design.