A facile and efficient preparation of pillararenes and a pillarquinone

Article abstract of DOI:10.1002/anie.200904765

Ring around the roses: The ipso substitution of benzene rings makes a simple and efficient synthesis of pillar[n]arenes (n=5, 6) possible. Pillar[6]arenes (see picture) and pillar[5]quinone, an oxidation product of pillar[5]arene, are novel highly promisi

Full text of DOI:10.1002/anie.200904765

Angewandte
Chemie
DOI: 10.1002/anie.200904765
Host–Guest Chemistry
A Facile and Efficient Preparation of Pillararenes and a
Pillarquinone**
Derong Cao,* Yuhui Kou, Jianquan Liang, Zhizhao Chen, Lingyun Wang, and Herbert Meier*
Calixarenes 1 and their derivatives have attracted consider-
able attention over the past two decades. This attention can be
attributed to their applications in areas as diverse as gas
adsorption,[1] nanotubes,[2] catalysis,[3] DNA recognition[4] and
fullerene chemistry.[5] Recently, many calixarene analogues
have been developed in supramolecular chemistry, such as
calixpyrroles,[6] thiacalixarenes,[7] and homooxacalixarenes.[8]
In contrast to the vast literature about the meta-bridged
cyclooligomers 1, very little is known about their para-bridged
analogues 2, called pillar[n]arenes (Scheme 1). Recently, the
cyclic pentamer 25 (R = OCH3). Ether cleavage with BBr3
affords the pillar[5]arene with free hydroxy groups 25 (R =
OH). The yields for the respective steps are poor (22.0 and
6.6%).[9,10]
We have now found a surprising reaction involving 2,5-
bis(benzyloxymethyl)-1,4-diethoxybenzene (3a), which was
treated in boiling dichloromethane with catalytic amounts of
p-toluenesulfonic acid (4). The reaction mixture turned green
and an oligomerization took place, delivering the cyclic
pentamer 25a and the acetal 5a in yields of 75 and 73%,
respectively, upon isolation (Scheme 2). Acids such as H2SO4
or H3PO4 can be used as catalysts as well, but non-oxidative
acids, such as HCl or the Lewis acid BF3·O(C2H5)2, do not
promote the reaction. ipso-Substitutions on benzene by a
dealkylation/alkylation mechanism are very rare, and they
can be observed either in electrochemical processes or in
reactions catalyzed by radical cations as one-electron oxi-
dants.[11]
Scheme 1. Calixarenes 1n and their para-bridged analogues 2n, which
are called pillararenes.
first two members 2n (n = 5, R = OCH3, OH) of this series
were reported.[9] They exhibit very interesting host–guest
properties, but their preparation is rather tedious; the Lewis
acid catalyzed condensation of 1,4-dimethoxybenzene and
paraformaldehyde furnishes a polymer, which contains some
[*] Prof. Dr. D. Cao, Y. Kou, J. Liang, Z. Chen, L. Wang
School of Chemistry and Chemical Engineering
South China University of Technology
Guangzhou 510640 (China)
Fax: (+86)20-8711-0245
E-mail: drcao@scut.edu.cn
Prof. Dr. H. Meier
Institute fꢀr Organische Chemie
Johannes Gutenberg-Universitꢁt Mainz
Duesbergweg 10-14, 55099 Mainz (Germany)
E-mail: hmeier@mail.uni-mainz.de
Scheme 2. Generation of ethyl-substituted pillar[5]arene 25a.
[**] This work is supported by the National Natural Science Foundation
of China (20572111), the Science and Technology Planning Project
of Guangdong Province (2007A010500011), and the Research Fund
for the Doctoral Program of Higher Education of China
(20060561024).
The exact mechanism of the generation of 25a and 5a is
not known. We assume a transition-state A in which the
interaction of 3a and 4 can lead to a (partial) charge transfer
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Table 2: Preparation of pillar[5]- and pillar[6]arenes with different alkoxy substituents R; R’=Et.
to generate a radical cation of 3a,
having a deep green color in solu-
tion, thereby enhancing the reactiv-
ity of the positions on the ring to
which alkyl groups are appended.
Furthermore, the acid facilitates the
À
benzyl ether cleavage, so that a C
C bond can be formed between the
benzylic carbon atom and the
carbon atom of the ring (dashed
line in A, Scheme 2). A four-fold
Starting compound
R
t [h]
Product Yield [%] M.p. [8C]
Product Yield [%] M.p. [8C]
3c
3 f
3g
Et
Me
nBu
3–4
1–2
15
25a
25b
25c
89
95
86
154–156
194–195
133–135
26a
8
–
11
172–173
–
87–89
cyclocondensation
would
still
[a]
–
involve geometrically strained
a
26c
transition state, so that the cyclo-
[a] Traces of higher cyclooligomers.
pentamerization is preferred. Cyc-
lizations of higher linear oligomers
can be less favorable, because of
higher activation entropies.
[1.1.1.1.1]cyclophane, which has been known for more than 20
years. However, the synthetic access to it is laborious and the
overall yields are below 1%.[12]
These first results encouraged us to optimize the prepa-
ration of pillararenes. p-Toluenesulfonic acid (4) in CH2Cl2
proved to be the best catalyst, as the acidity and the relatively
low redox potential of 4 are best suited for the cyclo-
condensation. Replacement of the benzyloxymethyl substitu-
ents by n-butyloxymethyl groups did not change the yield of
25a (Table 1). However, the use of less bulky leaving groups
Even more challenging was the oxidation of 25. When 25a
was treated with (NH4)2[Ce(NO3)6], the pillarquinone 65 was
produced (62%, m.p. > 2808C), representing the very first
cyclooligomeric quinone.
Table 1: Preparation of pillar[5]arene 25a by using different leaving
groups CH2OR’ and OR’.
Starting compound
R’
T [8C]
t [h]
Yield of 25a [%][a]
3a
3b
3c
3d
3e
Bn
nBu
Et
Me
H
41
41
RT
RT
RT
2
24
3–4
3–4
5–6
75
75
89
92
84
NMR and mass spectra (MALDI-TOF) were used for the
characterization of 25a–d, 26a,c, and 65. Table 3 shows a
1
comparison of the H and 13C NMR data of 3d, 25a, 26a, and
[a] Yield of isolated product.
65. The d values of the cyclopentamer 25a and the cyclo-
hexamer 26a are very similar. The number of the signals
such as methoxymethyl or ethoxymethyl groups afforded very
high product yields (92 and 89%, respectively) and permitted
short reaction times, even at room temperature. Free hydroxy
groups (3e) proved to be somewhat less favorable.
Table 3: 1H and 13C NMR data of 3d, 25a, 26a, and 65 (d values in CDCl3,
Me4Si as internal standard).
A detailed study of the reactions of starting compounds 3
with R = Me, Et, or nBu revealed a quantitative generation of
pillararenes. Apart from cyclic pentamers 25 as major
products, higher cyclooligomers 2n were formed as minor
components (Table 2). The overall yields of isolated products
were about 97% in each case. We used column chromatog-
raphy (SiO2, petroleum ether (b.p. 60–908C)/ethyl acetate
40:1) for the separation of the cyclooligomers. The hexamers
26a and 26c represent the first pillar[6]arenes.
Compd.
CqO
Cq
CH
6.90
CH2(O) OCH2 CH3
4.47 4.00 1.36
3d
1H
13C 150.3 126.6 112.5
69.2 64.5 15.0
25a
26a
65
1H
6.71
3.75
29.8
3.81
63.8
1.25
15.0
13C 149.8 128.5 115.1
1H
6.68
3.75
30.9
3.81
64.0
1.27
15.2
13C 150.4 127.8 115.2
Cleavage of the ether groups in 25 by the reaction with
BBr3 in CH2Cl2 (0–208C, 45 h) afforded compound 25d having
free hydroxy groups in 70% yield. Its parent system is
1H
6.75
3.48
26.3
13C 186.4 143.5 135.3
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interactions. Model considerations reveal that the empty
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10 ꢀ. The benzene ring rotation should decrease these cavity
extensions to about 5 and 7 ꢀ. The red cyclopentaquinone 65
has a similar freedom for intramolecular rotations and also
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1
yields just one each of a set of H and 13C NMR signals.
In conclusion, a novel, suprisingly simple, and quantitative
preparation of pillar[5]arenes 25 and the first pillar[6]arenes 26
was found. Oxidation with (NH4)2[Ce(NO3)6] afforded the
first cyclooligomeric quinone 65. The easy access to these
compounds should enable the investigation of various host–
guest relationships. The differently sized cavities of 25 and 26,
and the different electron densities of 25 and 65 promise
distinct selectivities for organic guest molecules. Moreover,
the comparison of pillar[n]arenes 25 and 26, and pillarquinone
65 with the corresponding calix[n]arenes and cucurbit[n]urils
appears to be exciting.[13]
Received: August 26, 2009
Published online: November 18, 2009
[10] After submission of this paper, we noticed two additional
5
ꢀ
compounds 2 (R = OTf and R = C CPh), which were obtained
Keywords: arenes · cyclooligomers · host–guest chemistry ·
in overall yields below 2%. See T. Ogoshi, K. Umeda, T.-A.
Yamagishi, Y. Nakamoto, Chem. Commun. 2009, 4874.
.
ipso-alkylation · quinones
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