Synthesis of pillar[7]arene

Article abstract of DOI:10.1016/j.cclet.2012.03.026

The first synthesis of pillar[7]arene is reported with two methods. Method A: the FeCl₃-catalyzed condensation reaction of 1,4-dimethoxybenzene (1) with paraformaldehyde in CHCl₃ gave dimethoxypillar[7]arene (3). Method B: the p-toluenesulfonic acid catalyzed condensation reaction of 2,5-bis(benzyloxymethyl)-1,4-dimethoxybenzene (2) in CH₂Cl ₂ gave compound 3. Demethylation of 3 with BBr₃ gave pillar[7]arene (4). The pillar[7]arene might be a perspective macrocyclic host in host-guest chemistry.

Full text of DOI:10.1016/j.cclet.2012.03.026

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 509–511
www.elsevier.com/locate/cclet
Synthesis of pillar[7]arene
Yu Chen a, Hong Qi Tao a, Yu Hui Kou a, Herbert Meier b, Jian Long Fu a, De Rong Cao a,
*
a School of Chemistry and Chemical Engineering, State Key Laboratory of Luminescent Materials and Devices, South China University of
Technology, Guangzhou 510641, China
b Institute of Organic Chemistry, University of Mainz, Duesbergweg 10-14, 55099 Mainz, Germany
Received 4 January 2012
Available online 18 April 2012
Abstract
The first synthesis of pillar[7]arene is reported with two methods. Method A: the FeCl3-catalyzed condensation reaction of 1,4-
dimethoxybenzene (1) with paraformaldehyde in CHCl3 gave dimethoxypillar[7]arene (3). Method B: the p-toluenesulfonic acid
catalyzed condensation reaction of 2,5-bis(benzyloxymethyl)-1,4-dimethoxybenzene (2) in CH2Cl2 gave compound 3. Demethyl-
ation of 3 with BBr3 gave pillar[7]arene (4). The pillar[7]arene might be a perspective macrocyclic host in host–guest chemistry.
# 2012 De Rong Cao. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Pillar[n]arenes; Pillar[7]arene; Host–guest chemistry; Condensation reaction; Iron(III) chloride
Pillar[n]arenes, a new family of para-bridged pillar-shaped cyclic molecules, were first reported by Ogoshi et al. in
2008 [1]. Since then, they have received great and continuous attention owing to their applications in host–guest
chemistry [1–3], self-assemble chemistry [4,5] and fluorescence chemistry [6]. At present, pillar[5]arenes, the so-
called ‘‘major’’ member of pillar[n]arenes, are prepared by the condensation reactions of 1,4-disubstituted
hydroquinones with formaldehyde in the presence of Lewis acid in good yield [7], which enabled them being
extensively investigated [8]. In contrast, the larger member of pillar[n]arenes are less well investigated mainly due to
cumbersome and low yielding synthetic procedures. In 2009, we first reported the synthesis of pillar[6]arenes by the p-
toluenesulfonic acid (TsOH) catalyzed condensation reaction of 2,5-bis(benzyloxymethyl)-1,4-dialkoxy-benzene in
8–11% yield [7]. In 2010, using a similar method, Huang et al. reported the synthesis of 1,4-diisobutoxypillar[6]arene
in 5% yield [9]. It is very difficult to prepare larger members of pillar[n]arenes. Therefore, synthesis of higher
members of the pillar[n]arenes is necessary and a challenge. The 7-membered ring of pillar[n]arenes, coded as
pillar[7]arene, is still unknown.
As part of our ongoing effort to develop efficient methods for synthesis of pillar[n]arenes [7,10,11], we herein
report the first synthesis of pillar[7]arene with two methods. Method A: the FeCl3-catalyzed condensation reaction of
1,4-dimethoxybenzene (1) with paraformaldehyde in CHCl3 gave dimethoxypillar[7]arene (3). Method B: the TsOH
catalyzed condensation reaction of 2,5-bis(benzyloxymethyl)-1,4-dimethoxybenzene (2) in CH2Cl2 gave 3.
Compound 3 was converted to pillar[7]arene (4) by demethylation with BBr3 (Scheme 1).
* Corresponding author.
E-mail address: drcao@scut.edu.cn (D.R. Cao).
1001-8417/$ – see front matter # 2012 De Rong Cao. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.03.026

510
Y. Chen et al. / Chinese Chemical Letters 23 (2012) 509–511
OMe
OMe
Method A
FeCl3, CHCl3
(HCHO)n
30 oC, 2_3 h
OMe
OH
BBr3, _15 oC to r.t.
H
1, 4-Dimethoxybenzene
H
1
48 h, 82 %
H
H
MeO
HO
OMe
7
7
Method B
OEt
Dimethoxypillar[7]arene
Pillar[7]arene
EtO
3
TsOH, CH2Cl2
r.t., 2 h
4
OMe
2, 5-Bis(ethoxymethyl)-1, 4-
dimethoxybenzene
2
Scheme 1. Synthesis of pillar[7]arene.
1. Experimental
All reagents and solvents were obtained from commercial sources and purified prior to use according to standard
solvent manual. Melting points were measured with a Tektronix X4 apparatus and uncorrected. 1H NMR (400 MHz)
and 13C NMR spectra were recorded with a Bruker DRX 400 spectrometer. Matrix-assisted laser desorption ionization
time-off flight (MALDI-TOF) mass measurements were performed with an Autoflex III smart-beam spectrometer.
Preparation of dimethoxypillar[7]arene (3): Method A: To a stirred mixture of 1,4-dimethoxybenzene 1 (0.415 g,
3.0 mmol) and paraformaldehyde (0.27 g, 9.0 mmol) in anhydrous CHCl3 (50 mL) was added anhydrous FeCl3
(63 mg, 0.39 mmol) under N2. The mixture was stirred at 30 8C. After completion of the reaction (monitored by TLC),
water (20 mL) was added. The aqueous layer was extracted with CH2Cl2 (2Â 10 mL) and the combined organic layers
were washed with 5% NaHCO3 (3Â 10 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure at
30 8C to afford a red solid. The crude mixture was purified by column chromatography (7:1 PE–EtOAc). Elution
yielded two fractions: the first fraction was dimethoxypillar[5]arene as a white solid (16 mg, 3.6%); the second
fraction was 3 as a white solid (31 mg, 6.8%). mp: 252–253 8C. 1H NMR (400 MHz, CDCl3): d 6.61 (s, 14H, Ar–H),
3.82 (s, 14H, CH2-bridge), 3.59 (s, 42H, CH3). 13C NMR (100 MHz, CDCl3): d 151.5, 127.5, 114.0, 56.1, 31.0. MS
(ESI): m/z 1073.5 [M+Na]+. MS (APCI): m/z 1051.5 [M+H]+. MS (MALDI-TOF): m/z calcd. for [M]+ C63H70O14:
1050.5; found 1050.6; calcd. for [M+Na]+: 1073.5; found 1073.6. Anal. Calcd. for C63H70O14ÁCH2Cl2: C, 67.66%; H,
6.39%; found: C, 66.81%; H, 6.47%. Method B: 2,5-bis(benzyloxymethyl)-1,4-dimethoxybenzene 2 (5.23 g,
20.6 mmol) and p-toluenesulfonic acid monohydrate (500 mg, 2.63 mmol) were stirred in 400 mL CH2Cl2 at room
temperature for 2 h. Then H2O (100 mL) was added and the water layer was separated and extracted with CH2Cl2 (3Â
15 mL). The combined organic phase was dried (Na2SO4) and purified by column chromatography (7:1 PE–EtOAc).
Elution yielded two fractions: the first fraction was dimethoxypillar[5]arene as a white solid (2.94 g, 95%); the second
fraction was 3 as a white solid (75 mg, 2.4%).
Preparation of pillar[7]arene (4): To a stirred solution of 3 (0.105 g, 0.1 mmol) in CH2Cl2 (5 mL, freshly distilled
from CaH2) at À15 8C under N2 was added over 30 min a solution of BBr3 (0.4 mL, 4.2 mmol) in anhydrous CH2Cl2
(4 mL). The reaction mixture was allowed to warm slowly to room temperature and stirred for 48 h. The reaction
mixture was quenched by addition of saturated NaHCO3 (20 mL). The resulting precipitate was collected and washed
with 0.5 mol/L aqueous HCl and CH2Cl2 to give a white solid. The crude product was purified by column
1
chromatography (1:1 chloroform–acetone) to afford 4 as a white solid (70 mg, 82%). mp: 152 8C (dec.). H NMR
(400 MHz, DMSO-d6): d 8.45 (s, 14H, OH), 6.41 (s, 14H, Ar–H), 3.51 (s, 14H, CH2). 13C NMR (100 MHz,
CD3COCD3): d 148.4, 126.7, 117.8, 30.3. MS (MALDI-TOF): m/z calcd. for [M]+ C49H42O14: 854.0; found 854.0.
2. Results and discussion
Scheme 1 shows the synthetic procedure and the chemical structures of dimethoxypillar[7]arene (3) and
pillar[7]arene (4). Recently we reported a directed and improved protocol for the synthesis of pillar[6]arene in

Y. Chen et al. / Chinese Chemical Letters 23 (2012) 509–511
511
moderate yield in an FeCl3–CHCl3 (catalyst–solvent) system [11]. Much to our surprise, we found that the
FeCl3–CHCl3 system is efficient for the synthesis of the larger pillar[7]arene (3) by improving the reaction conditions
and the purification process. Using 1.3 equiv. of anhydrous FeCl3 as catalyst gave a mixture of dimethoxypillar
[5]arene, 3 and polymer. For the synthesis of 3 from 1,4-dimethoxybenzene (1), the amount of catalyst plays a key role
to control reaction rate. We monitored the reaction using silica gel thin layer chromatography (TLC, PE/EtOAC = 3/
1). Spots correlating to dimethoxypillar[5]arene and 3 were observed at Rf = 0.53 and 0.47, respectively. Particularly
noteworthy was that these reaction conditions were apparently quite sensitive to temperature, water and the
concentration of the reactant. When the reaction temperature was low (25 8C) or the solvent was not dry, no product
was found. The product was isolated by column chromatography on silica gel with PE/EtOAC = 7/1 as the eluent. Its
structure was characterized by 1H NMR, 13C NMR, ESI-mass, APCI-mass and MALDI-TOF-mass. Furthermore, we
also employed other alkyloxybenzenes (e.g. 1,4-dibutoxybenzene) as starting material to synthesize the corresponding
pillar[7]arenes. Unfortunately, the corresponding pillar[7]arenes were not found.
In 2009, we reported efficient method for synthesis of pillar[5]arenes by condensation reaction of 2 with TsOH as
catalyst in high yield [7]. After a detailed study of the synthetic method, we found that it can also be applied for
preparation of 3, even though the yield is low.
The solubility of 3 in organic solvents is similar to dimethoxypillar[5]arene. However, pillar[7]arene (4) can easily
be dissolved in polar organic solvents. It should be mentioned that 4 is easily oxidized, therefore should be stored
under nitrogen.
In summary, dimethoxypillar[7]arene and pillar[7]arene, the two new members of the pillar[n]arene family, were
first obtained by simple synthetic routes. These larger pillar[7]arenes provide new opportunities for the development
of host–guest relations because the larger cavity size of the pillar[7]arene hosts will permit a special discrimination
between guests. Further studies on host–guest chemistry of pillar[7]arenes are in progress.
Acknowledgment
This work was supported by the National Natural Science Foundation of China (Nos. 20872038 and 21072064).
References
[1] T. Ogoshi, S. Kanai, S. Fujinami, et al. J. Am. Chem. Soc. 130 (2008) 5022.
[2] C.J. Li, X.Y. Shu, J. Li, et al. J. Org. Chem. 76 (2011) 8458.
[3] Y.H. Yu, X.B. Hu, L. Chen, et al. Chem. Commun. 47 (2011) 4694.
[4] F.H. Huang, Z.B. Zhang, Y. Luo, et al. Angew. Chem. Int. Ed. 50 (2011) 1397.
[5] Z.X. Chen, W. Si, X.B. Hu, et al. Tetrahedron Lett. 52 (2011) 2484.
[6] J.F. Stoddart, N.L. Strutt, R.S. Forgan, et al. J. Am. Chem. Soc. 133 (2011) 5668.
[7] D.R. Cao, Y.H. Kou, J.Q. Liang, et al. Angew. Chem. Int. Ed. 48 (2009) 9721.
[8] P.J. Cragg, K. Sharma, Chem. Soc. Rev. 41 (2012) 597.
[9] C. Han, F. Ma, Z. Zhang, et al. Org. Lett. 12 (2010) 4360.
[10] L. Liu, D. Cao, Y. Jin, et al. Org. Biomol. Chem. 9 (2011) 7007.
[11] H.Q. Tao, D.R. Cao, L.Z. Liu, et al. Sci. China Chem. 55 (2012) 223.