(345c) Novel Crown Ether with Bulky and Rigid Subunits: Experimental and Theoretical Alkali Metal Selectivity Studies

Crown ethers (CEs) are unique macrocylic compounds capable of forming strong complexes with metal ions which fit well into the cavity of the CE. Because of this size-match selectivity, CEs had been studied in the fields of phase transfer catalysis, metal sensing and metal ion extraction. Among the CE class, twelve to 14 membered CE rings are known to form stable complexes with lithium (Li⁺) in both organic and aqueous solutions even in the presence of other alkali metal ions. Specifically, dibenzo-14-crown-4 ether (DB14C4) and its derivatives are known as Li⁺ complexant because of its ideal cavity dimension (1.2-1.5 Å) for complexation with Li⁺ (1.2 Å). The two benzo groups provide rigidity that lessens its affinity with bigger alkali metal ions such as sodium (Na⁺, 2.0 Å) potassium (K⁺, 2.7 Å) and cesium (Cs⁺, 3.34 Å).DB14C4 has only been applied as carriers in electrodes with moderate sensitivity towards Li⁺ or as a carrier in liquid-liquid extraction (LLE) systems due to its difficult synthesis involving multiple reaction steps and low over-all yields. Although efforts have been made to develop new efficient methods for DB14C4 synthesis, complexation with larger metal ions is still inevitable due to the formation ofâ??sandwichâ?-type complex lowering its selectivity towards Li⁺.

To address this issue, a new class of 14-crown-4 ether containing two bulky subunits has been synthesized to prevent the formation of sandwich type CE-metal ion complex formation. The bulky subunits are designed to act as blocking moieties, which hinder the complexation with bigger metal ions. As formation of 1:1 CE-metal ion complex is promoted, enhanced Li⁺ selectivity was achieved compared to its rigid type counterpart. However, decomplexation of metal ions is difficult due to steric hindrance and limiting interaction of water or other solvents with the metal ion once it is inside the cavity of the bulky CE. This was alleviated by designing CEs with one bulky moiety but the selectivity was greatly compromised due to flexibility of the CE backbone. Moreover, the overall yield is very poor because of difficulty in the ring closure reactions when using bulky tertiary diols as starting substrate.

Herein, intermolecular cyclization of bulky bis-epoxide with 1,2-dihydroxybenzene was performed to synthesize novel lithium selective 14 membered CE having both rigid and bulky subunits. The rigid aromatic groups enhanced the rigidity of 14-crown-4 ether backbone while the bulky subunits provided a blocking mechanism to prevent bigger metal ions to from a complex as well to alleviate the formation of higher ordered sandwich type complexes. The reaction route was optimized by changing the reaction solvents, temperature, and catalyst using commercially available bis-epoxides, neopentyl diglycidyl ether (2a) and 1,4-butanediol diglycidyl ether (2b). The synthesized CEs with different bulky structures were assessed by experimental LLE and theoretical density functional theory calculations (DFT) to understand the effect of the bulky structures. Parameters obtained from the DFT calculations such as cavity size, oxygen to metal ion (O-M⁺) distances as well as metal ion binding energies (Î?E_M+) were investigated to correlate with the metal ion selectivity obtained from the experimental extraction results.

Efficient synthesis of the di-hydroxy CEs (3a-h) via intermolecular cyclization of bulky bis-epoxide with 1,2-dihydroxybenzene was achieved using t-BuOH as solvent with the appropriate metal hydroxide catalyst that fits the cavity size of the target CE. The bulky bis-epoxide intermediate was synthesized via etherification of the bulky diols (2,2-diethyl1,3-propanediol, pinacol, bicyclopentyldiol, cis-1,2-cyclohexanediol, cis-cyclopentanediol and 1,2-dihydroxybenzene) with allyl bromide to obtain di-alkene intermediates (1c-h). Subsequent oxidation of the di-alkene intermediate with a peroxy-acid (m-CPBA) gave bis-epoxide intermediates (2c-h).The structures of the synthesized CEs and intermediates were confirmed by ¹H and ¹³C NMR, FTIR, and HRMS. The alkali metal (Li⁺, Na⁺, K⁺, Cs⁺) complexing abilities of CEs 3a-h was assessed by liquid-liquid extraction of alkali metal perchlorates in dichloromethane-water system and reported as metal distribution (D_M+) and selectivity (α_Li/M+). All the CEs synthesized showed high Li⁺ distribution but dihydroxy-benzotetramethyl-14-crown-4 ether (3d) and dihydroxy-benzo-bicylopentyl-benzo-14-crown-4 ether (3e) having bulky tetramethyl and bicyclopentyl respectively, showed highest Li⁺ selectivity in the presence of other alkali metals. Furthermore, no D_K+ and D_Cs+ were analyzed for 3d and 3e. Selectivity of α_Li/Na=3344 and α_Li/Na=2512 achieved for 3d and 3f, respectively is among the highest in the literature. In comparison to DB14C4 having both rigid moieties, showed distribution not only towards Li⁺ but also with bigger alkali metals. The complexation of DB14C4 towards bigger metals can be attributed to the formation of 2:1 sandwich type complex.It is noteworthy to mention that CE dihydroxy-benzo-neopentyl-15-crown-4 ether (3a) and dihydroxy-benzo-16-crown-4 ether (3b) with a 15 and 16-crown-4 membered ring respectively, showed preferences towards Na⁺due to a bigger cavity size.

To explain the metal ion preference behavior of the synthesized CEs with bulky and rigid structures as well as the tendency of the CEs to form sandwich type complexes, DFT calculations was employed. The lowest energy structures of the synthesized free CE as well as the binding energies of the 1:1 or the 2:1 CE-metal ion sandwich type complex were determined using the Vienna ab initio simulation package (VASP) described by the Perdew-Burke-Ernzerhof (PBE) generalized gradient functional and the projector augmented wave (PAW) method.

The cavity size of the synthesized CEs is defined as the empty space at the center of the CE hetero atoms and was estimated as the average distance of the opposite heteroatoms subtracted by the Van der Waals radius of oxygen atoms (1.4 Å). Among the CEs synthesized, 3d and 3e have ideal cavity sizes (1.2 Å and 1.21 Å respectively) for Li⁺ having an ionic diameter of 1.2 Å. The results complement the experimental LLE which could be the main reason for the high Li⁺ selectivity. Bigger cavity sizes were obtained for 3a, 3b and 3c (1.36, 1.63, and 1.34 Å respectively) which also possess high distribution with the bigger Na⁺due to the bigger 15-16 membered ring formed.

The average O-M⁺ distances were also determined to assess the stability of the complex. The results showed larger O-M⁺ distances on the bulky side of the CE compared to the rigid side especially for 3d and 3e with K⁺ and Cs⁺ complexes. On the other hand, a typical CE-metal ion complex (DB14C4-Li⁺) showed equal O-M⁺ distances in both sides. Similar trend was also observed in DB14C4-Li⁺ crystal structures available in the literature. Thus, the bulky groups present in the synthesized CEs provide steric hindrance and hence destabilizing complexes with bigger metal ions as revealed by the varying O-M⁺distances in the bulky and rigid side. In addition, the bulky structures could also prevent formation of sandwich type complexes.

To confirm the tendency of the synthesized CEs to form 1:1 or 2:1 CE complex, a simple enthalpy exchange reaction mechanism (Î?H_M+) towards other alkali metals (Na⁺, K⁺ and Cs⁺) with respect to Li⁺ in the presence of water was calculated based on the DFT binding energies. The results showed high preference towards Li⁺ due to a positive Î?H_Na+, Î?H_K+, and Î?H_Cs+ calculated for the 1:1 CE-metal ion complex. However, for the 2:1 complex, only 3d and 3e showed positive Î?H_M+suggesting that 3d and 3e prevented the formation of sandwich type complexes.

In summary, novel lithium selective 14-16 membered crown-4 ethers having both bulky and rigid subunits were synthesized in high yields via intermolecular cyclization of the bulky bis-epoxide intermediate with 1,2-dihydroxybenzene under basic conditions. Experimental LLE showed that 3d and 3e had the highest Li⁺ selectivity which can be attributed to their comparable cavity size with Li⁺ diameter estimated by DFT calculations. DFT calculations also showed instability of complexes towards bigger metal ions (Na⁺, K⁺, Cs⁺) due to the effect of the bulky structure providing bigger O-M⁺ distances. The bulky subunits not only prevented the formation of higher ordered complexes but also fine-tuned the cavity size of the CE. The potential of these types of CEs having both rigid and bulky functionality as selective chelates for selective sensing or extraction of Li⁺in dilute solution such as seawater is currently under investigation.

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (2015R1A2A1A15055407) and by the Ministry of Education (No. 2009-0093816).