Novel process for selective separation of trace artemisitene from artemisinin by ammonium functional ionic liquids

Abstract

One of the challenges to obtain high‐quality natural active substances is the selective separation of the target compound from its analogues. In this study, ionic liquids (ILs), with design flexibility, were proposed to separate artemisitene and artemisinin, typical examples of natural analogues. Based on COSMO‐RS calculation, several ILs were selected to separate artemisitene/artemisinin by experiment. It was demonstrated that the aqueous solution of N‐allyl‐N,N,N‐trimethylammonium chloride ([AA][Cl]) exhibited excellent capability for selective separation of the two compounds. Under the optimal conditions (40°C, 1 h), the separation selectivity of artemisitene/artemisinin could reach 12.23 when the initial impurity content was only 0.8 wt%. Spectroscopic analysis and molecular dynamics indicated that π–π complexation between artemisitene and [AA][Cl] plays a major role in this separation process. Moreover, the process of multistage cross‐flow extraction was compared with counter‐flow extraction, and the latter one exhibited advantages in energy consumption and product yield.

Design of Dual Stimuli-Responsive Copolymerized Ionic Liquid with Flexible Phase Transition Temperature and Its Application in Selective Separation of Artemisitene/Artemisinin

“…However, in the systems containing copolymerized ILs, the concentration of ARE in the extraction phase (the PIL phase), D ARE and S ARE/ART , increased with the increase of IL content in the copolymerized IL. The good separation efficiency could be attributed to π–π complexation between the copolymerized IL and ARE as illustrated in our previous work by spectroscopic analysis and simulation . Besides, we also illustrated that hydrogen bonding between the copolymerized IL and ARE (Figure S11, Supporting Information) also plays a role in this separation process.…”

“…The standard curves and methods for quantitative determination of ARE and ART concentrations by HPLC followed our previous study …”

“…Therefore, isopropyl acrylamide was introduced into the copolymer as the thermal-responsive group. ILs containing imidazole and benzene ring was used as the IL monomer based on the theory that π–π complexation between IL and ARE facilitated the separation of ART/ARE . Copolymerized ILs containing various ratios of IL to isopropyl acrylamide were prepared, which were characterized by NMR and TGA.…”

“…Moreover, this method requires a large amount of organic solvents like petroleum ether and ethyl acetate with high volatility and explosive property. In our previous work, the aqueous ammonium IL solution was demonstrated to exhibit excellent performance in separation of ART/ARE, but the recovery of IL from water was difficult and energy-consuming …”

A synergistic ‘push and pull’ ionic liquid biphasic system for enhanced extraction separation of cholic acid and deoxycholic acid

“…[25][26][27] Recent work has demonstrated that ILs containing specific anions and cations can recognize even subtle structural motifs such as hydroxyl groups, 28,29 aromatic rings, 30 and chirality, 31,32 successfully separating various isomers, homologues, and stereoisomers. 6,[33][34][35] However, the vast majority of studies focus solely on the rational molecular design of the IL extractant through systematic variation of anion, cation, and alkyl chains. [36][37][38] The potential synergistic effects of strategically designing the feedstock solvent along with the IL have been largely ignored.…”