Continuous flow hydrogenation of methyl and ethyl levulinate: an alternative route to γ-valerolactone production.

Heterogeneous continuous transformation of methyl levulinate (ML) and ethyl levulinate (EL) to γ-valerolactone (GVL), as a promising C5-platform molecule was studied at 100°C. It was proved that the H-Cube® continuous hydrogenation system equipped with 5% Ru/C CatCart® is suitable for the reduction of both levulinate esters. While excellent conversion rates (greater than 99.9%) of ML and EL could be achieved in water and corresponding alcohols, the selectivities of GVL were primarily affected by the solvent used. In water, 100% conversion and ca 50% selectivity that represent ca 0.45 molGVL gmetal -1 h-1 productivity towards GVL, were obtained under 100 bar of total system pressure. The application of alcohols as a solvent, which maintained high conversion rates up to 1 ml min-1 flow rate, resulted in lower productivities (less than 0.2 molGVL gmetal -1 h-1) of GVL. Therefore, from a synthesis point of view, the corresponding 4-hydroxyvalerate esters could be obtained even at a higher reaction rate. The addition of sulfonated triphenylphosphine ligand (TPPTS) allowed reduction of the system pressure and resulted in the higher selectivity towards GVL.

Continuous-flow high pressure hydrogenation reactor for optimization and high-throughput synthesis.

This paper reports on a novel continuous-flow hydrogenation reactor and its integration with a liquid handler to generate a fully automated high-throughput hydrogenation system for library synthesis. The reactor, named the H-Cube, combines endogenous hydrogen generation from the electrolysis of water with a continuous flow-through system. The system makes significant advances over current batch hydrogenation reactors in terms of safety, reaction validation efficiency, and rates of reaction. The hydrogenation process is described along with a detailed description of the device's main parts. The reduction of a series of functional groups, varying in difficulty up to 70 degrees C and 70 bar are also described. The paper concludes with the integration of the device into an automated liquid handler followed by the reduction of a nitro compound in a high throughput manner. The system is fully automated and can conduct 5 reactions in the time it takes to perform and workup one reaction manually on a standard batch reactor.