Six‐membered cyclic carbonates from trimethylolpropane: Lipase‐mediated synthesis in a flow reactor and in silico evaluation of the reaction

Abstract

Six-membered cyclic carbonates with hydroxyl and methoxycarbonyloxy functional groups were prepared by transesterification of trimethylolpropane (TMP) with dimethylcarbonate (DMC) by solvent-free lipase-mediated flow reaction followed by thermal cyclization. The flow reaction efficiency was evaluated using different configurations of reactor consisting of packed beds of Novozym®435 (immobilized Candida antarctica lipase B-CalB-a.k.a. N435) and molecular sieves, flowrate, and biocatalyst loads. The mixed column of the biocatalyst and molecular sieves, allowing rapid and efficient removal of the by-product-methanol-was the most efficient setup. Higher conversion (81.6%) in the flow reaction compared to batch process (72%) was obtained using same amount of N435 (20% (w/w) N435:TMP) at 12 h, and the undesirable dimer and oligomer formation were suppressed. Moreover, the product was recovered easily without extra separation steps, and the biocatalyst and the molecular sieves remained intact for subsequent regeneration and recycling. The reaction of CalB with DMC and the primary transesterification product, monocarbonated TMP, respectively, as acyl donors was evaluated by in silico modeling and empirically to determine the role of the enzyme in the formation of cyclic carbonates and other side products. DMC was shown to be the preferred acyl donor, suggesting that TMP and its carbonated derivatives serve only as acyl acceptors in the lipase-catalyzed reaction. Subsequent cyclization to cyclic carbonate is catalyzed at increased temperature and not by the enzyme. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:375-382, 2017.

Novozym 435: the “perfect” lipase immobilized biocatalyst?

“…305 Six-membered cyclic carbonates with methoxycarbonyloxy and hydroxyl functionalities were obtained via transesterification of trimethylolpropane or dimethyl carbonate in a solvent-free medium flow reaction using N435, followed by thermal cyclization (yields over 80%). 306 Octyl ethanoate has been produced via ultrasound-assisted transesterification catalyzed by N435 and using vinyl acetate as an activated acyl donor in a solvent-free medium (yield over 97%). 307 Other papers compared both esterification and transesterification routes.…”

Batch and Continuous Flow Production of 5-Hydroxymethylfurfural from a High Concentration of Fructose Using an Acidic Ion Exchange Catalyst

“…The latter system used a very low fructose concentration (6.7 wt %) and a high ratio of the catalyst (1 equiv) and [Bmim]Cl (15 equiv) at 75 °C for 20 min to yield 93% HMF . Using heterogeneous catalysts including, ion exchange resins, in packed-bed reactors in a recirculating batch or continuous mode has been shown to be more efficient, e.g., for the production of biodiesel, fructose–oleic acid esters, and cyclic carbonates. − Recently, even the continuous flow production of HMF from fructose has been successfully demonstrated using the ion exchange catalyst Amberlyst-15. , However, these dehydrations were also performed using relatively low fructose concentration (5 wt %) in 1,4-dioxane/DMSO (9:1 v/v) and isopropyl alcohol/DMSO mixed-solvent systems, respectively.…”

Flow Chemistry: Towards A More Sustainable Heterocyclic Synthesis

“…They used a combination of immobilized Candida antarctica lipase B (N435) and molecular sieves (MS) to promote a rapid conversion to the desired products, when compared to batch production. Further, they verified that during the biocatalytic process, DMC works as the preferred acyl donor, while TMP and its carbonated derivatives work as acyl acceptors in an enzyme‐dependent manner, with the cyclization step being temperature‐dependent …”