Facilitated solvent screening for membrane-based extraction of chiral amines via a priori simulations

Abstract

Chiral amines are important building blocks in the pharmaceutical industry. A challenge for the current industry is their difficult synthesis procedures, which employ harsh operating conditions or have an unfavourable equilibrium constant. An interesting strategy in improving the reaction equilibrium is the use of in-situ product removal via membrane extraction (ME) using supported liquid membranes (SLM), which is explored in this work. More specifically, the separation of the product amines α-methylbenzylamine (MBA) and 1-methyl-3-phenylpropylamine (MPPA) from the donor amine isopropyl amine (IPA) by employing SLMs is investigated in this study. A difficulty in SLM-applications is the solvent selection, which mostly requires the use of extensive liquid–liquid extraction (LLE) testing. In this work, COSMO-RS is used to perform a fast and simplified screening of almost 400 ILs, which led to a shortlist definition of fourteen ILs. For these fourteen ILs, critical solvent properties (i.e., density, viscosity and phase miscibility) were analysed experimentally and compared to simulations in COSMO-RS. Finally, four promising ionic liquids were selected for further LLE- and ME-testing, namely trihexyltetradecylphosphonium bis(trifluoromethylsulfonyl)imide ([P6,6,6,14][N(Tf)2]), 1-methyl-1-propylpyrro-lidinium bis(trifluoromethylsulfonyl)imide ([C3mPyr][N(Tf)2]), 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([C6mim][N(Tf)2]) and triethylsulfonium bis(trifluoromethylsulfonyl)imide ([S2,2,2][N(Tf)2]). Based on wettability testing of four polymeric porous substrates (i.e., PTFE, PES, PSf and PVDF), the PTFE-support was chosen for the stability tests, due to its very high hydrophobicity. The LLE- and stability tests showed that [P6,6,6,14][N(Tf)2] has the highest MBA/IPA- and MPPA/IPA-selectivity and the best SLM-stability of all the tested ILs. Comparative SLM-testing with the benchmarking solvent undecane showed that the IL [P6,6,6,14][N(Tf)2] has a higher SLM-selectivity than undecane at elevated temperatures, while no decrease in its stability was observed.