Influence of process parameters on extraction equilibria for the chiral separation of amines and amino‐alcohols with a chiral crown ether

Abstract

Reactive extraction is studied as a promising chiral separation technique for commercial production scale. For chiral separation of amines and amino alcohols, a chiral crown ether was identified as a versatile enantioselective extractant. In this paper, the influence of various process conditions on the extraction performance is studied experimentally, and a predictive model is constructed based on the chemical and physical equilibria. It was found that the operational selectivity in one extraction step is mainly determined by the complexation constants between crown ether and enantiomers (which are dependent on solvent and temperature) and by the extractant concentration, whereas the distribution ratio is also strongly influenced by the pH. The model gives an excellent prediction of the operational selectivity and a good explanation for the system's responses to changes in process conditions. The model can be used as a basis for a multistage equilibrium extractor model and for conceptual process design. Under optimal process conditions, an operational selectivity >1.5 was obtained for five out of seven model compounds, with satisfying distribution ratios (D ∼ 1-10).

Modelling and experimental evaluation of reaction kinetics in reactive extraction for chiral separation of amines, amino acids and amino-alcohols

“…The reversible reaction between enantiomer R and crown ether C is known to have 1:1 stoichiometry (Naemura et al, 1998) and is described as R +C ⇔ RC. It is known from previous equilibrium measurements (Steensma et al, 2006b) that only R (and S) partition between the aqueous and the organic phase and that C and RC remain in the organic phase, so the reaction only takes place in the organic phase. It was assumed that the rate equation can be defined according to the law of mass action as a (1, 1)-reaction…”

“…Selective extractants for these substances are hardly available. After identification, the equilibrium behaviour of a newly identified system should be determined (Steensma et al, 2006b).…”

Equilibrium Studies on Reactive Extraction of α‐Cyclohexyl‐mandelic Enantiomers Using Hydrophilic β‐Cyclodextrin Derivatives Extractants

“…24 The influence of organic solvent on distribution behavior was investigated in various extraction systems containing 0.1 mol/L HP-β-CD in aqueous phase and α-CHMA enantiomers in different organic solvents at 5 ℃. It was observed from Table 1 that the solvent has a clear influence on the distribution ratios and enantioselectivity.…”

Modeling multiple chemical equilibrium for reactive extraction of naproxen enantiomers with HP-β-CD as hydrophilic selector

“…For example, in a 99% pure product (R/S=100), about 190 NTU (number of transfer units) are required with the value of  equals 1.05, the number will decrease to approximately 30 when  increases to a value of 1.20 [7]. Several chiral extractants, such as tartaric acid derivatives [4,7], crown ethers [5,6,14] as well as others [15] have been used for separation of enantiomers. However, the enantioselectivities of the chiral extractants are somewhat low, and a large number of transfer units is required in chiral solvent extraction processes.…”

“…Compared with the methods mentioned above, chiral solvent extraction is usually considered as a promising alternative, which is cheaper and easier to scale up to commercial scale and has a large range of applications. Many researchers have attempted the separation of optically active compounds by chiral solvent extraction in recent years [4][5][6][7][8][9][10][11][12][13][14]. Although lots of reports are available for enantioselective extraction, only a few provide fundamental insights in the reaction engineering mechanisms [11][12][13][14].…”