Synthesis of novel calixcrown derivatives with

selective complexation towards cesium ions

Lu Zhang a, Juan Du a, Li Hua Yuan a, Dong Zhang b,Gui Ping Dan b, Yuan You Yang a, Wen Feng a,*

a Key Laboratory for Radiation Physics and Technology of Ministry of Education, College of Chemistry, Institute of Nuclear Science and

Technology, Sichuan University, Chengdu 610064, Chinab Institute of Nuclear Physics and Chemistry, CAEP, Mianyang 621900, China

Available online 22 December 2010

Abstract

A series of novel calix[4]arenecrown-6 derivatives with an alkenyl loop of various sizes 5–8 were synthesized via intramolecular

ring closing olefin metathesis and characterized by 1H NMR, 13C NMR and ESI-HRMS. Their complexation property towards

cesium ion was studied by 1H NMR technique. Two-phase extraction of alkali metal ions using UV–vis spectroscopy revealed

remarkably different extractabilities. These results indicate that the complexation capacities towards cesium ions can be tuned and

controlled through cooperative regulation of the strain of the loop and conformational change of calixcrown skelton.

# 2010 Wen Feng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Keywords: Calixcrowns; Olefin metathesis; Cesium ions; Extraction

Calix[4]crowns belong to a large class of calixarene derivatives that attracted intense interests in the past decades

due to the excellent complexation capacities towards metal ions [1]. Among them, 1,3-alternate calix[4]crowns exhibit

highly binding affinities towards alkali and alkaline earth metal cations compared to other conformational isomers [2].

Variation of size of crown ether loops [3], introduction of substituents [4,5] with potential coordination sites via the

other side of the molecule, and attachment of proton-ionizable groups [6] to the surroundings of the polyether ring,

lead to a striking change in binding capability.

When calix[4]arene is locked in 1,3-alternate conformation with a crown moiety on one end, the potential impact

upon complexation from the other side results. For example, calix-biscrown compounds have been shown to have even

worse extractability than calix-monocrowns in spite of the presence of two cavities for capturing two metal ions [7]. In

these cases, both electrostatic repulsion between the two metal ions and the induced conformation change of the

binding sites were accountable for the unfavourable binding of the second metal ion. The interplay mediated through

cations between the two loops from both sides suggests the possible manipulation of the binding effectiveness via

varying the loop structure, size, and electronic properties of the pendent groups. Thus, calixcrowns singly bridged with

a simple alkyl or alkenyl loop of various sizes may serves as a probe to systematically examine the influence of the

strain on the overall conformation, and therefore, the complexation behavior towards metal ion. The ring closing

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Chinese Chemical Letters 22 (2011) 284–287

* Corresponding author.

E-mail address: wfeng9510@scu.edu.cn (W. Feng).

1001-8417/$ – see front matter # 2010 Wen Feng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

doi:10.1016/j.cclet.2010.10.004

metathesis (RCM) involving the use of Grubbs catalyst provided a direct and simple one-step strategy towards

synthesis of many compounds including heterocycles and acyclic diene or enyne precursors and so on [8]. One

example via RCM was reported about the synthesis of singly or doubly-bridged calix[4]arenes and oligocalix[4]arenes

[9]. Herein, we report the synthesis of a series of novel calix[4]arenecrown-6 with an alkenyl loop of different size 5–8

and the complexation behavior towards cesium ions as compared to 3b–3e in a bid to correlating the strain of the loop

and the binding effect, and affording an explanation for the difference in selectivity due to cooperative regulation and

conformational change in the calixcrown skeletons.

The synthetic route of compounds 5–8 was shown in Scheme 1. 1,3-Alternate calix[4]monocrown-6 derivatives 3a–

3e were prepared from the reaction of calix[4]arene 1 with alkenyl bromide firstly in the presence of K2CO3 [10],

followed by addition of the poly(ethylene glycol) ditosylate [11] in the presence of Cs2CO3. Compounds 5–8 were

obtained by intramolecular ring closing olefin metathesis of 3b–3e with the first generation Grubbs catalyst in high

yields (83–90%). The olefin metathesis of compound 3a failed to afford compound 4 mainly because the length of the

alkenyl chain of compound 3a was too short to force the ring closure. The structures of all the products and

intermediates were characterized by 1H NMR, 13C NMR and ESI-HRMS. The 1,3-alternate conformation of 3–8 were

evidenced by an observation of a singlet of the ArCH2Ar at around 38 ppm in 13C NMR spectra. In addition, the single

peak pattern of the ArCH2Ar methylene protons in the 1H NMR spectroscopy also provided a convenient indicator for

the formation of 1,3-alternate conformers. The structures of compounds 5–8 were further confirmed by reduction to

their corresponding derivatives. For example, hydrogenation of 5 or 8 afforded compounds with [M + NH4]+ of 914.5626

and 1082.7461, respectively, indicating that the double bond in the loop was reduced to saturated –CH2CH2–.

Compound 5: white solid, yield 83%; 1H NMR (400 MHz, CDCl3): d 7.07 (d, 4H, J = 7.4 Hz), 7.02 (d, 4H,

J = 7.4 Hz), 6.95 (t, 2H, J = 7.4 Hz), 6.85 (d, 1H, J = 7.9 Hz), 6.74 (m, 4H), 4.07 (m, 2H), 4.06–4.07 (m, 4H,), 3.93 (d,

8H, J = 17.0 Hz), 3.71 (s, 4H), 3.53–3.56 (t, 4H, J = 5.2 Hz), 3.42–3.45 (dt, 4H, J = 9.9, 5.9 Hz), 2.84–2.79 (m, 4H,),

2.47 (d, 2H, J = 6.6 Hz). 13C NMR (100 MHz, CDCl3): d 157.54, 157.08, 149.27, 147.53, 135.93, 133.65, 133.53,

133.49, 132.94, 129.02, 128.64, 128.60, 127.79, 122.87, 122.66, 122.59, 122.42, 117.14, 115.94, 70.24, 69.97, 69.79,

69.37, 68.02, 66.30, 41.18, 39.68, 38.77, 38.57, 32.96, 32.37, 28.92, 25.46, 23.14, 14.26, 10.89. ESI-HRMS (m/z)

calcd. for C56H66O8 (M+) 866.4758; found: 884.5086 (M + NH4)+, 889.4642 (M + Na)+.

Compound 6: white solid, yield 85%; 1H NMR (400 MHz, CDCl3): d 7.06 (d, 4H, J = 7.3 Hz), 7.01 (d, 4H,

J = 7.3 Hz), 6.90–6.79 (m, 3H), 6.79–6.71 (m, 4H), 5.25 (s, 2H), 4.10 (d, 4H, J = 3.5 Hz), 3.96–3.82 (m, 8H), 3.74 (s,

4H), 3.56 (s, 4H), 3.50 (t, 4H, J = 6.8 Hz), 2.92 (s, 4H), 2.47 (d, 2H, J = 6.5 Hz). 13C NMR (100 MHz, CDCl3): d157.31, 156.37, 149.21, 147.49, 135.95, 133.99, 133.46, 129.66, 129.52, 129.07, 122.79, 122.70, 122.60, 117.16,

115.92, 70.23, 70.15, 69.99, 69.33, 69.05, 68.26, 41.16, 39.66, 38.39, 32.34, 30.73, 28.89, 25.43, 24.31, 23.11, 14.22,

10.85. ESI-HRMS (m/z) calcd. for C58H70O8 (M+) 894.5071; found: 912.5404 (M + NH4)+, 933.4673 (M + K)+.

Compound 7: white solid, yield 90%; 1H NMR (400 MHz, CDCl3): d 7.02 (dd, 8H, J = 7.2, 3.0 Hz), 6.88 (d, 1H,

J = 8.0 Hz), 6.82 (t, 2H, J = 7.4 Hz), 6.77 (d, 2H, J = 9.1 Hz), 6.75–6.67 (m, 2H), 5.42–5.31 (m, 1H), 5.17 (s, 1H), 4.04

L. Zhang et al. / Chinese Chemical Letters 22 (2011) 284–287 285[()TD$FIG]

Scheme 1. Reagents and conditions: (a) Br(CH2)nCH CH2, K2CO3, CH3CN, reflux; (b) bis-1,2-[20(200-hydroxyethoxy)ethoxy]-4-(2-ethylhexyl)-

benzene di-p-toluenesulfonate, Cs2CO3, reflux, 30 h; (c) the first generation Grubbs catalyst, dry CH2Cl2, reflux, 6–8 h.

(s, 4H), 3.90–3.75 (m, 8H), 3.56 (dd, 4H, J = 8.7, 4.1 Hz), 3.46 (dt, 8H, J = 14.7, 5.7 Hz), 3.34 (q, 4H, J = 5.7 Hz), 2.47

(t, 2H, J = 10.8 Hz) 13C NMR (100 MHz, CDCl3): d 155.67, 155.54, 155.39, 147.95, 146.34, 134.81, 133.28, 133.23,

132.69, 132.65, 129.77, 128.87, 128.36, 128.16, 128.10, 121.62, 121.45, 121.38, 121.21, 116.35, 114.86, 69.28, 69.14,

68.83, 68.69, 68.52, 68.32, 52.44, 40.07, 38.59, 37.20, 31.98, 31.28, 28.70, 28.33, 27.82, 27.73, 26.39, 24.69, 24.39,

23.31, 22.05, 13.18, 9.82. ESI-HRMS (m/z) calcd. for C60H74O8 (M+) 922.5384; found: 940.5707 (M + NH4)+,

945.5276 (M + Na)+, 961.5021 (M + K)+.

Compound 8: pale yellow solid, yield 90%; 1H NMR (400 MHz, CDCl3): d 7.03 (t, 8H, J = 6.7 Hz), 6.88 (d, 1H,

J = 7.9 Hz), 6.76–6.81 (m, 4H), 6.65–6.70 (m, 2H), 5.37 (s, 2H), 4.08 (d, 4H, J = 12.3 Hz), 3.79 (d, 8H, J = 16.9 Hz),

3.67 (d, 4H, J = 3.5 Hz), 3.58 (s, 4H), 3.51 (d, 4H, J = 4.5 Hz), 3.39 (d, 4H, J = 6.7 Hz), 2.48 (d, 2H, J = 6.4 Hz). 13C

NMR (100 MHz, CDCl3): d 156.98, 156.53, 148.81, 147.20, 135.77, 134.28, 134.14, 133.91, 130.92, 130.10, 129.94,

129.80, 129.62, 129.49, 122.51, 122.36, 122.19, 116.92, 115.40, 77.48, 77.17, 76.85, 70.74, 70.34, 70.29, 69.93,

41.19, 39.71, 38.17, 37.94, 32.39, 32.18, 30.12, 29.80, 29.73, 29.51, 29.47, 29.34, 29.26, 28.97, 28.93, 28.86, 28.31,

26.66, 25.96, 25.83, 25.49, 23.14, 14.26, 10.90. ESI-HRMS (m/z) calcd. for C70H94O8 (M+) 1062.6949; found:

1080.7164 (M + NH4)+, 1085.6858 (M + Na)+, 1101.6429 (M + K)+.

The complexation efficiencies of 5–8 were investigated by 1H NMR technique using solvent extraction of solid

cesium picrate into chloroform under neutral conditions. The CDCl3 solutions of 5–8 were mixed with solid cesium

picrate [12] and the mixtures were stirred at room temperature. The low percentage extraction (E%) was observed for

compound 5 (27% E) after 12 h. This may be attributable to the high strain of the alkenyl loop where the bridge is too

short causing an induced conformation change that makes it unfavourable for the crown ether to coordinate properly

with metal ions. In stark contrast, the extraction of compound 7 (63.0% E) was much more efficient and the percentage

extraction varied little from that of compound 8 (63.5% E). This could be explained by the larger size and flexibility of

the loop, which has released much of the strain as observed in compound 5, leading to almost the same extraction

efficiency between 7 and 8.

Solvent extraction experiments [13] were performed to see the changes of the binding capacity before and after the

ring-closing reactions by UV–vis spectroscopy. The percentage extraction of hosts from water into CHCl3 at

25 � 1 8C was determined according to Pedersen’s procedure [14]. Among the alkali metal ions examined, the

percentage extraction of Li+, Na+, K+, Rb+ were too low to analyze the binding difference of 5–8. The percentage

extraction of compounds 3b–3e was almost in the same level, suggesting that the extraction abilities were not affected

by the lengths of open alkenyl chains. However, as shown in Fig. 1, the percentage extraction of compounds 5–8 with

coupled alkenyl chains was within the range of 0.91% and 28.31%, but all below that of 3b–3e (ca. 30%),

demonstrating that the lengths of alkenyl chains and ring closure dramatically affected the binding ability. No marked

difference was observed for compounds 7 (25.57%) and 8 (28.31%). These observations are consistent with the results

from 1H NMR extraction experiments. The different extraction efficiency revealed between compounds 3b–3e and 5–

8 again indicated that the size and strain (or rigidity) of the alkenyl loop formed via ring-closure metathesis reaction

L. Zhang et al. / Chinese Chemical Letters 22 (2011) 284–287286

[()TD$FIG]

3e3d3c3b87650

5

10

15

20

25

30

35

40

45

50

Perc

enta

ge e

xtra

ctio

n (E

%)

Host

Cs+

Fig. 1. Extraction capacity of calix[4]crown derivatives towards cesium picrate.

constitute an important factor in selective complexation of cesium ions. The strain from the alkenyl loop and the

induced conformational change of the calixarene skeleton should function cooperatively for the observed results of

extraction.

In conclusion, we have synthesized four novel calixcrown derivatives 5–8, which show obvious differences of

binding capacity towards Cs+. The design of calixcrowns with appropriate alkenyl or alkyl loops on one side may be

utilized to induce a conformational change of the crown moiety on the other side, making it possible to tune and

control the complexation ability of calixcrowns towards cesium ions.

Acknowledgments

This work was financially supported by Institute of Nuclear Physics and Chemistry of CAEP (No. HG2008061),

and Analytical & Testing Center of Sichuan University for NMR analysis.

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