# New Trends in Separation Techniques of Lithium Isotopes: A Review of Chemical Separation Methods
## 1 Introduction
### Separation Using Crown Ethers  
Several studies have confirmed the good separation effect of macrocyclic compounds like crown ether (CE) and its derivatives on Li isotopes. The principle of this separation is that the solvation environments of the cations are quite different when a metal salt is distributed between an immiscible solvent containing a macrocyclic compound and an aqueous solution.  
Due to their unique cavity structures and size effect, the separation factor of \({}^{6}\)Li/\({}^{7}\)Li (the \(\alpha\) value) by crown ethers is comparable to that of the Li amalgam method. However, the relatively weak interaction of crown ethers with Li\({}^{+}\) leads to a low distribution coefficient of Li (DLi, 10\({}^{-2}\)-10\({}^{-5}\)), especially for crown ethers with small cavities such as 12-crown-4 (12C4), B12C4, whereas these crown ethers generally demonstrate much higher \(\alpha\) values. Another challenge is the loss of CE molecules during the extraction procedure. Several studies have reported the separation of \({}^{6}\)Li/\({}^{7}\)Li isotopes using solvent extraction with crown ethers [18; 19]. The selection of crown ethers must consider their cavity sizes that must closely match that Li\({}^{+}\) ionic diameter [20; 21]. Furthermore, it was shown that due to the dipole-ion interactions between the donor O atoms and Li\({}^{+}\), the cavity sizes of free 12C4, 15C5, and 18-Crown-6 (18C6) crown ethers decrease upon their coordination with Li\({}^{+}\) ion [22]. Therefore, crown ethers with large cavities such 15C5, 18C6, and DC18C6 could be chosen for their higher distribution coefficient.  
For example, [PERSON] et al. investigated the Li isotopic effects of 12C4, B15C5, and dicyclohexano-18-crown-6 (DC18C6) with solvent extraction and found that the smaller-cavity-sized crown ethers have a greater separation factor [19]. The separation factor for 12C4-CHCl\({}_{3}\)/LiI-H\({}_{2}\)O system was reported to be 1.057 at 0 \({}^{\circ}\)C, while D\({}_{\mathrm{Li}}\) was only 2.0 \(\times\) 10\({}^{-5}\), lower than that of B15C5 and DC18C6 (10\({}^{-2}\)-10\({}^{-3}\)). Due to the low distribution of Li for 12C4 crown ether, the 15C5 crown ether and its derivates have been used in recent studies. Some studies tried the development of covalently grafted functional materials, which can significantly reduce the loss of CE molecules. For example, [PERSON] et al. (2016) used grafted NH\({}_{2}\)-B15C5 on mesoporous silica SBA-15 and investigated the adsorptive separation behaviour of \({}^{6}\)Li/\({}^{7}\)Li [23].  
A more recent strategy (called ion-pair strategy) was developed by [PERSON] et al. to create an efficient phase transfer of Li\({}^{+}\) by crown ethers. In this system, FeCl\({}_{3}\) salt, known as a strong Lewis acid, was introduced for Cl\({}^{-}\) binding to form [FeCl\({}_{4}\)]\({}^{-}\) anion, and B12C4 or B15C5 acted as Li\({}^{+}\) receptor [24]. The presence of tetrachloridoferrate ([FeCl\({}_{4}\)]\({}^{-}\)) as counter anion was presented, which helps to overcome the Hofmeister bias and facilitates the efficient transfer of Li\({}^{+}\) from extremely hydrophilic chlorides (see Figure 1).  
Upon the coupling effects of electrostatic and ion-dipole interactions, this new strategy showed an unprecedented distribution of Li\({}^{+}\) in the solvent extraction process. An exceptionally high D\({}_{\mathrm{Li}}\) of 54 was achieved by [PERSON] et al., 2021 for benzo-15-crown-5 (B15C5), surpassing those of solvent extraction from solely Li salt aqueous solution. In this study,the maximum \({}^{6}\)Li/\({}^{7}\)Li separation factors (\(\alpha\)) of 1.038 and 1.049 were obtained for B15C5 and benzo-12-crown-4 (B12C4) in dichloroethane at 273 K [24].