Lithium halide ion-pair recognition with halogen bonding and chalcogen bonding heteroditopic macrocycles

Article abstract of DOI:10.1039/d1cc01287h

A series of halogen bonding and chalcogen bonding phenanthroline containing heteroditopic macrocyclic receptors exhibit cooperative recognition of lithium halide (LiX) ion-pairs. Quantitative 1H NMR ion-pair titration experiments in CDCl3?:?CD3CN (1?:?1,

Full text of DOI:10.1039/d1cc01287h

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Lithium halide ion-pair recognition with halogen
bonding and chalcogen bonding heteroditopic
macrocycles†
Cite this: DOI: 10.1039/d1cc01287h
Received 9th March 2021,
Accepted 14th April 2021
Yuen Cheong Tse, Andrew Docker, Zongyao Zhang and Paul D. Beer
*
DOI: 10.1039/d1cc01287h
rsc.li/chemcomm
A series of halogen bonding and chalcogen bonding phenanthroline facilitating the extraction and recovery of a range of transition-9–13
containing heteroditopic macrocyclic receptors exhibit cooperative and alkali-metal salts.14–18 However, reports of employing this
1
recognition of lithium halide (LiX) ion-pairs. Quantitative H NMR ion- strategy towards extracting lithium salts, in particular, remain
pair titration experiments in CDCl3 :CD3CN (1 : 1, v/v) reveal a co-bound scarce.19–23 In general, heteroditopic receptor design typically relies
lithium cation switches on halide anion binding, most notably with the on crown ether-based cation recognition sites and convergent
halogen bonding host system. The employment of bis- iodo- and hydrogen bond donor arrays as anion binding sites.24,25 Over the
telluromethyl-triazole sigma–hole donor motifs endows contrasting last decade the emergence of sigma–hole interactions, such as
halide anion selectivity and binding affinity, with the halogen bonding halogen bonding (XB) and chalcogen bonding (ChB), have gained
ditopic host capable of exclusively binding lithium chloride whereas the increasing attention in the field of anion recognition.26–35 Despite
chalcogen bonding ditopic receptor displays notable selectivity for the noteworthy enhancements in anion affinity and marked con-
lithium iodide over lithium bromide. Preliminary solid–liquid extraction trasting selectivity behaviour frequently observed relative to hydro-
experiments demonstrate the potential of sigma–hole mediated ion- gen bonding (HB) analogues, the strategic integration of sigma–hole
pair recognition as a promising strategy for lithium salt recovery.
donors in heteroditopic ion-pair receptor design is extremely
rare.36–41
Lithium constitutes a crucial element in modern life. Its
Herein, we report a series of novel XB, ChB and HB 1,
pervasive application in energy storage materials, polymer 10-phenanthroline-based macrocycles, that serve as heterodi-
manufacture and pharmacology have stimulated an ever- topic ion-pair hosts for the cooperative recognition and solid–
increasing demand for the requisite lithium precursors. Con- liquid extraction of lithium halide salts (Fig. 1). Importantly,
temporary methods of obtaining lithium typically rely on the incorporation of a bidentate XB donor motif dramatically
mineral reserves, such as brine and ore deposits, which by increases the potency of the ditopic receptor for lithium halide
virtue of their accessibility and low processing costs have
continued to dominate the global supply of lithium.1 Whilst
the abundance of these natural resources presents no immedi-
ate threat, the continued exploitation of primary sources cur-
rently employed to meet this ever-growing demand raises
significant environmental and ecological concerns.2–4 Indeed,
despite the evident motivation for developing strategies reco-
vering lithium from extant non-natural sources (e.g. disposed
electrical devices),5–7 only o5% of lithium-ion batteries are
recycled.8 The judicious exploitation of heteroditopic molecular
receptors, capable of simultaneously binding cationic and
anionic species, has demonstrated enormous potential in
Chemistry Research Laboratory, Department of Chemistry, University of Oxford,
Mansfield Road, Oxford, OX1 3TA, UK. E-mail: paul.beer@chem.ox.ac.uk
† Electronic supplementary information (ESI) available: Synthesis, structural
Fig. 1 Structure of target phenanthroline-based heteroditopic macro-
cycles incorporated with sigma–hole donors designed for ion-pair recog-
nition of lithium salts. AÀ = anion.
characterisation, additional figures. CCDC 2069372 and 2068373. For ESI and
crystallographic data in CIF or other electronic format see DOI: 10.1039/
d1cc01287h
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recognition, remarkably facilitating the challenging stabilisation
of LiCl ion-pairs in organic solvent media. In stark contrast, the
ChB heteroditopic receptor displays a pronounced selectivity
preference towards the ‘softer’ LiI ion-pair.
The synthesis of the target heteroditopic macrocyclic hosts
is outlined in Scheme 1. The bis-triazole anion binding sites
were constructed via a CuAAC42,43 ‘click’ reaction between the
appropriately appended alkyne precursors 231,44 and two
equivalents of azide 3 which gave the corresponding methox-
ymethyl (MOM) acetal protected precursors 4, in excellent
yields in the range of 77–95%. Acidic deprotection afforded
the bis-phenols 5 in quantitative yields. The target ditopic
receptors 1ÁXB, 1ÁChB and 1ÁHB were prepared via macrocycli-
zation reactions between 1,10-phenanthroline bis-tosylate 645
and respective bis-phenols 5 in the presence of Cs2CO3 in dry
DMF under high-dilution conditions in yields of up to 54%
after chromatographic purification. All novel macrocycles were
Fig. 2 Crystal structures of 1ÁXB (left) and 1ÁHB (right). XB interaction between
an iodine atom (purple) and a methanol solvate is shown in 1ÁXB. Hydrogen
atoms are omitted for clarity. Gray = carbon, blue = nitrogen, and red = oxygen.
binding. A representative example with 1ÁXB is shown in Fig. 3a.
Upon addition of LiClO4, downfield shifts of phenanthroline
proton signals 5–7 were indicative of Li+ complexation. Subse-
quent addition of TBACl caused a gradual downfield shift of
internal benzene proton 2. This is consistent with the endotopic
binding of ClÀ occurring in the vicinity of the XB anion binding
cavity of the macrocycle. Analogous experiments with TBABr and
TBAI elicited similar chemical shift perturbations, indicating the
concomitant binding of ion-pairs (Fig. S4-5 and S4-6, ESI†). In the
case of 1ÁChBÁLiClO4 and 1ÁHBÁLiClO4, the addition of TBABr and
TBAI caused significant perturbations of the respective TeCH3 and
triazole protons suggesting LiBr and LiI ion-pair binding. However,
adding TBACl to both receptor lithium metal complex solutions
resulted in LiCl salt precipitation (Fig. S4-7–S4-10, ESI†).
1
characterised by H, 13C and 125Te NMR (where relevant) and
high-resolution ESI mass spectrometry.
Crystals suitable for X-ray diffraction analysis were obtained by
slow evaporation of a solution of 1ÁXB in chloroform/methanol
mixture and by vapour diffusion of pentane into a chloroform
solution of 1ÁHB (Fig. 2).46 Inspection of the two structures reveals
that the two iodo-triazole groups in 1ÁXB are significantly more
twisted out of the plane relative to the central aromatic aryl spacer
compared to the proto-triazoles in 1ÁHB. Notably, the potency of
the XB-donor was revealed by the observation of a IÁÁÁO short
contact between the iodo-triazole donor and a methanol solvate
molecule, exhibiting a distance significantly shorter than the sum
of the van der Waals radii (87%).
Analogous qualitative 1H NMR titrations of 1ÁXB with one
equivalent of NaClO4 or KClO4 gave similar perturbations in the
phenanthroline signals indicative of successful metal cation
complexation. Subsequent addition of TBACl, however, caused
salt precipitation and recovery of the free macrocycle, high-
lighting the preference for the Li+ cation which is particularly
impressive considering the sizeable lattice enthalpy of LiCl
(834 kJ molÀ1) driving salt recombination (Fig. S4-11 and
S4-12, ESI†).47
To assess the ion-pair binding properties of the macrocycles,
preliminary qualitative 1H NMR binding investigations were
undertaken in 1 : 1 CDCl3 : CD3CN. Initial halide anion titration
experiments conducted on the free macrocycles indicated no
halide binding in this mixed solvent system.
The addition of one equivalent of LiClO4, followed by the
sequential addition of one, two and five equivalents of tetrabuty-
lammonium (TBA) halide salts, however, provided evidence for
macrocycle phenanthroline-bound Li+ switching on halide anion
Scheme 1 Synthesis of heteroditopic macrocycles 1ÁXB, 1ÁChB and 1ÁHB.
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Fig. 3 Left: Truncated 1H NMR spectra in 1 : 1 CDCl3 :CD3CN showing the aromatic regions of free receptor 1ÁXB, upon addition of 1 equivalent LiClO4 and
subsequent addition of 1, 2 and 5 equivalents of TBACl. Right: Anion binding isotherms of 1ÁXB in the presence of one equivalent of LiClO4 monitoring the
chemical shift of internal benzene proton 2 as a function of halide anion concentration, [host] = 1 mM and [guest] = 50 mM (298 K, 1 : 1 CDCl3 :CD3CN).
Table 1 Anion association constants (Ka/MÀ1) for 1ÁXB, 1ÁChB and 1ÁHB in
Quantitative analysis of the lithium halide ion-pair binding
properties of the ditopic receptors was carried out in the same
the presence of 1 equivalent of LiClO4 in 1 : 1 CDCl3 : CD3CNa
solvent system by monitoring the proton chemical shift pertur-
Anion
Cation
1ÁXB
1147 (3)
1214 (3)
1236 (13)
1ÁChB
—
186 (6)
662 (10)
1ÁHB
—
211 (6)
121 (6)
bation of the Li+ complexed macrocycles as a function of halide
anion concentration (Fig. 3b and Fig. S4-13–S4-18, ESI†). Bind-
fit analysis of the titration binding isotherm data determined
1 : 1 stoichiometric anion association constants (Table 1).48
Importantly, Table 1 reveals a significant lithium cation-
halide anion ion-pair binding cooperativity effect via a combi-
nation of favourable co-bound metal cation–anion electrostatic
attractions and macrocycle preorganisation resulting from Li+
ClÀ
BrÀ
IÀ
Li+
Li+
Li+
b
b
a
Ka values calculated using Bindfit software using a 1 : 1 host–guest
binding model. Errors (%) are in parenthesis. Lithium cation added as
LiClO4. All anions added as their TBA salts. Solvent = 1 : 1 CDCl3 :
b
CD3CN. T = 298 K. Salt recombination.
complexation. Comparing the halide anion association con- subsequently filtered off and CD3CN (200 mL) was added to
1
stant data, 1ÁXB is the most potent ion-pair receptor for all improve the resolution of the post-extraction H NMR spectra.
halides investigated, exhibiting two- to seven-fold enhance- Inspection of the 1H NMR spectra (Fig. 4) confirmed the
ments in BrÀ and IÀ affinities relative to ChB and HB analo- solubilisation of all three lithium halides by 1ÁXB as evidenced
gues. Notably, the potency of the XB donor motif is further by significant downfield perturbations of the macrocycle’s
illustrated by the ability of 1ÁXB to simultaneously complex the phenanthroline aromatic protons 5–7 and internal benzene
‘hard’ LiCl ion-pair, while analogous experiments with 1ÁChB proton 2, analogous to the 1H NMR spectra obtained from
and 1ÁHB resulted in LiCl salt precipitation. This may be sequential addition of equimolar of LiClO4 and TBA halide salt
rationalised by the strong XB-driven complexation of ClÀ, (Fig. 2). Likewise, 1ÁChB and 1ÁHB solubilised all three lithium
thereby inhibiting its recombination with the co-bound Li+. halides as revealed by similar downfield proton chemical shifts
Interestingly, 1ÁXB demonstrates similar strong ion-pair bind- in the respective 1H NMR spectra (Fig. S5-2 and 3, ESI†). These
ing for both the heavier halides with a modest preference over preliminary observations highlight the real potential for sigma–
chloride. By stark contrast, the ChB macrocyclic receptor, hole heteroditopic macrocycles to act as solid–liquid extrac-
1ÁChB, displays significant selectivity for the ‘softer’ LiI ion- tants for lithium salts.
pair over LiBr (Ka(IÀ)/Ka(BrÀ) = 3.5) which may be attributed to a
In conclusion, a series of XB, ChB and HB heteroditopic
combination of factors including heteroditopic host-ion-pair macrocyclic receptors consisting of a 1,10-phenanthroline
guest size complementarity and favourable ChB interactions cation binding site and XB/ChB/HB donors for binding anions
between the Te atoms and the larger IÀ anion.49,50
were synthesised for lithium halide salt ion-pair recogni-
The ability for the heteroditopic macrocycles to solubilise tion. Extensive 1H NMR titration experiments reveal the co-
inorganic lithium halide salts into organic solvent media was complexation of lithium cation switches on sigma–hole XB and
investigated by preliminary solid–liquid extraction studies. In a ChB halide recognition. The XB heteroditopic macrocycle proved
typical experiment, excess solid lithium halide salt was added to be the most potent LiX ion-pair receptor, impressively facilitat-
to a solution of macrocycle 1ÁXB in CDCl3 (600 mL) and the ing the binding of the ‘hard’ LiCl ion-pair species. Furthermore
mixture was vigorously sonicated for 1 hour. The excess salt was the incorporation of ChB donors significantly enhanced selectivity
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´
13 M. Alfonso, A. Espinosa, A. Tarraga and P. Molina, Org. Lett., 2011,
13, 2078–2081.
14 P. D. Beer, P. K. Hopkins and J. D. McKinney, Chem. Commun., 1999,
1253–1254.
´
15 H. Jiang, C. Dolain, J.-M. Leger, H. Gornitzka and I. Huc, J. Am.
Chem. Soc., 2004, 126, 1034–1035.
16 J. M. Mahoney, K. A. Stucker, H. Jiang, I. Carmichael,
N. R. Brinkmann, A. M. Beatty, B. C. Noll and B. D. Smith, J. Am.
Chem. Soc., 2005, 127, 2922–2928.
17 Z.-H. Sun, F.-F. Pan, Triyanti, M. Albrecht and G. Raabe, Eur. J. Org.
Chem., 2013, 7922–7932.
18 B. Akhuli and P. Ghosh, Chem. Commun., 2015, 51, 16514–16517.
19 S. Tsuchiya, Y. Nakatani, R. Ibrahim and S. Ogawa, J. Am. Chem. Soc.,
2002, 124, 4936–4937.
20 J. M. Mahoney, A. M. Beatty and B. D. Smith, Inorg. Chem., 2004, 43,
7617–7621.
21 Q. He, Z. Zhang, J. T. Brewster, V. M. Lynch, S. K. Kim and
J. L. Sessler, J. Am. Chem. Soc., 2016, 138, 9779–9782.
22 Q. He, N. J. Williams, J. H. Oh, V. M. Lynch, S. K. Kim, B. A. Moyer
and J. L. Sessler, Angew. Chem., Int. Ed., 2018, 57, 11924–11928.
23 K.-I. Hong, H. Kim, Y. Kim, M.-G. Choi and W.-D. Jang,
Chem. Commun., 2020, 56, 10541–10544.
Fig. 4 Comparative pre- and post-extraction 1H NMR spectra of 1ÁXB
with excess solid LiCl, LiBr and LiI (500 MHz, 298 K, 3 : 1 CDCl3 : CD3CN).
˜
24 Q. He, G. I. Vargas-Zu´niga, S. H. Kim, S. K. Kim and J. L. Sessler,
Chem. Rev., 2019, 119, 9753–9835.
25 A. McConnell, A. Docker and P. Beer, ChemPlusChem, 2020, 85,
1824–1841.
towards the ‘softer’ lithium halide salts namely LiI over LiBr. In
general, the HB heteroditopic macrocycle analogue demonstrated
inferior affinity for LiBr and LiI halide ion pairs relative to the
sigma–hole hosts. Preliminary lithium halide solid–liquid extrac-
tion studies revealed the potential for these heteroditopic macro-
cycles to solubilise solid lithium halide salts into organic solvent
mixtures. Importantly, these results demonstrate the exciting
potential of sigma–hole mediated ion-pair recognition for mod-
ulating both ion-pair affinity and selectivity.
Y. C. T. thanks the Croucher Foundation for a scholarship,
A. D. thanks the EPSRC for a studentship (Grant reference
number EP/N509711/1) and Z. Z. thanks China Scholarship
Council and University of Oxford for a scholarship.
´
26 T. A. Barendt, A. Docker, I. Marques, V. Felix and P. D. Beer,
Angew. Chem., Int. Ed., 2016, 55, 11069–11076.
27 Z.-X. Liu, Y. Sun, Y. Feng, H. Chen, Y.-M. He and Q.-H. Fan,
Chem. Commun., 2016, 52, 2269–2272.
28 C. J. Massena, N. B. Wageling, D. A. Decato, E. Martin Rodriguez,
A. M. Rose and O. B. Berryman, Angew. Chem., Int. Ed., 2016, 55,
12398–12402.
29 D. Mungalpara, S. Stegmu¨ller and S. Kubik, Chem. Commun., 2017,
53, 5095–5098.
´
30 J. Y. C. Lim, I. Marques, V. Felix and P. D. Beer, Chem. Commun.,
2018, 54, 10851–10854.
31 A. Borissov, I. Marques, J. Y. C. Lim, V. Felix, M. D. Smith and
´
P. D. Beer, J. Am. Chem. Soc., 2019, 141, 4119–4129.
32 T. Bunchuay, A. Docker, A. J. Martinez-Martinez and P. D. Beer,
Angew. Chem., Int. Ed., 2019, 58, 13823–13827.
33 J. Y. C. Lim and P. D. Beer, Chemistry, 2018, 4, 731–783.
34 J. Pancholi and P. D. Beer, Coord. Chem. Rev., 2020, 416, 213281.
35 M. S. Taylor, Coord. Chem. Rev., 2020, 413, 213270.
36 A. Mele, P. Metrangolo, H. Neukirch, T. Pilati and G. Resnati, J. Am.
Chem. Soc., 2005, 127, 14972–14973.
Conflicts of interest
¨
¨
37 R. Tepper, B. Schulze, P. Bellstedt, J. Heidler, H. Gorls, M. Jager and
U. S. Schubert, Chem. Commun., 2017, 53, 2260–2263.
There are no conflicts to declare.
38 A. Brown, K. M. Mennie, O. Mason, N. G. White and P. D. Beer,
Dalton Trans., 2017, 46, 13376–13385.
39 T. Bunchuay, A. Docker, U. Eiamprasert, P. Surawatanawong, A. Brown
and P. D. Beer, Angew. Chem., Int. Ed., 2020, 59, 12007–12012.
Notes and references
¨
1 G. Martin, L. Rentsch, M. Hock and M. Bertau, Energy Storage Mater.,
´
´
2017, 6, 171–179.
40 P. Sabater, F. Zapata, B. Lopez, I. Fernandez, A. Caballero and
P. Molina, Dalton Trans., 2018, 47, 15941–15947.
2 J. Nriagu, Encylopedia of Environmental Health, Elsevier, 2nd edn,
2019.
3 V. Flexer, C. F. Baspineiro and C. I. Galli, Sci. Total Environ, 2018,
639, 1188–1204.
4 W. Liu, D. B. Agusdinata and S. W. Myint, Int. J. Appl. Earth Obs.
Geoinf., 2019, 80, 145–156.
5 M. Kamenica, R. Kothur, A. Willows, B. Patel and P. Cragg,
Sensors, 2017, 17, 2430.
41 A. Docker, T. Bunchuay, M. Ahrens, A. J. Martinez-Martinez and
P. D. Beer, Chem. – Eur. J., 2021, DOI: 10.1002/chem.202100579.
42 J. E. Hein, J. C. Tripp, L. B. Krasnova, K. B. Sharpless and V. V. Fokin,
Angew. Chem., Int. Ed., 2009, 48, 8018–8021.
43 H. A. Stefani, S. N. S. Vasconcelos, F. Manarin, D. M. Leal, F. B. Souza,
L. S. Madureira, J. Zukerman-Schpector, M. N. Eberlin, M. N. Godoi
and R. de Souza Galaverna, Eur. J. Org. Chem., 2013, 3780–3785.
6 X. Zheng, Z. Zhu, X. Lin, Y. Zhang, Y. He, H. Cao and Z. Sun, 44 T. Nishikawa, S. Shibuya, S. Hosokawa and M. Isobe, Synlett, 1994,
Engineering, 2018, 4, 361–370. 485–486.
7 C. Liu, J. Lin, H. Cao, Y. Zhang and Z. Sun, J. Cleaner Prod., 2019, 45 C. J. Chandler, L. W. Deady and J. A. Reiss, J. Heterocycl. Chem., 1981,
228, 801–813.
18, 599–601.
8 B. Swain, Sep. Purif. Technol., 2017, 172, 388–403.
9 D. J. White, N. Laing, H. Miller, S. Parsons, P. A. Tasker and S. Coles,
Chem. Commun., 1999, 2077–2078.
10 K. Maity, D. K. Panda, R. J. Gallup, C. K. Choudhury and S. Saha,
Org. Lett., 2018, 20, 962–965.
46 CCDC 2069372 (1ÁXB) and 2068373 (1ÁHB) contain the supplemen-
tary crystallographic data for this paper†.
47 J. R. Rumble, CRC Handbook of Chemsistry and Physics, CRC Press,
99th edn, 2018.
48 P. Thordarson, Chem. Soc. Rev., 2011, 40, 1305–1323.
´
11 Y. Chen, D.-X. Wang, Z.-T. Huang and M.-X. Wang, Chem. Commun., 49 J. Y. C. Lim, I. Marques, A. L. Thompson, K. E. Christensen, V. Felix
2011, 47, 8112. and P. D. Beer, J. Am. Chem. Soc., 2017, 139, 3122–3133.
12 B. Hua, L. Shao, Z. Zhang, J. Liu and F. Huang, J. Am. Chem. Soc., 50 D. J. Pascoe, K. B. Ling and S. L. Cockroft, J. Am. Chem. Soc., 2017,
2019, 141, 15008–15012.
139, 15160–15167.
Chem. Commun.
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