Synthesis of triple-ringed [14]arene via dynamic covalent chemistry mechanism in condensation reaction of phenols with m-Benzenedicarbaldehyde

Article abstract of DOI:10.1246/cl.2012.699

Condensation reaction of 2-methylresorcinol with m-benzenedicarbaldehyde in the presence of HCl as a catalyst in n-propanol at 90 °C for 48 h proceeded via a dynamic covalent chemistry (DCC) mechanism to afford a triple-ringed [14]arene in 52% yield.

Full text of DOI:10.1246/cl.2012.699

doi:10.1246/cl.2012.699
Published on the web June 23, 2012
699
Synthesis of Triple-ringed [14]Arene via Dynamic Covalent Chemistry Mechanism
in Condensation Reaction of Phenols with m-Benzenedicarbaldehyde
³
Hiroyuki Seki, Shingo Kuwabara, Hiroto Kudo,*,³³ and Tadatomi Nishikubo
Department of Material and Life Chemistry, Faculty of Engineering, Kanagawa University,
Rokkakubashi, Kanagawa-ku, Yokohama, Kanagawa 221-8686
(Received March 6, 2012; CL-120192; E-mail: kudoh@kansai-u.ac.jp)
R2
Condensation reaction of 2-methylresorcinol with m-ben-
zenedicarbaldehyde in the presence of HCl as a catalyst in
n-propanol at 90 °C for 48 h proceeded via a dynamic covalent
chemistry (DCC) mechanism to afford a triple-ringed [14]arene
in 52% yield.
R1
R3
OHC
CHO
+
R4
m-benzenedicarb-
aldehyde
Run
1
R1 R2 R3
R4
2-Methylresorcinol
Resorcinol
OH CH3 OH
H
H
2
OH
H
H
OH
H
Dynamic covalent chemistry (DCC), which involves rever-
sible covalent bond formation, is a powerful tool for the
construction of covalently linked nanostructures.1 DCC selec-
tively provides the most thermodynamically stable molecules
under appropriate reaction conditions and can be used to
construct three-dimensional cage structures in a one-pot proce-
dure. Imine bond formation,2,3 boronic acid condensation,4,5
alkoxy amine exchange,6 ester bond exchange,7 acetal bond
exchange,8 and disulfide bond exchange9 have been utilized to
synthesize unique, covalently linked nanostructures via the DCC
mechanism. Zhang and his co-workers employed the DCC
approach to selectively obtain a three-dimensional cage structure
by means of imine bond formation reaction of triamine with
dialdehyde using Sc(OTf)3 as a catalyst in chloroform at room
temperature. Interestingly, this cage showed highly selective
adsorption of CO2 over N2 under standard temperature and
pressure (STP, 20 °C, 1 bar).10
3
p-Cresol
OH
OH
CH3
4
p-tert-Butylphenol
H
H
t-C(CH3)3
CH3
CH3
OH HO
CH3
OH HO
H3C
HO
CH3
OH
OH OH OH
HO
Run 1
HO
OH
CH3
OH HO
OH HO
CH3
OH HO
CH3
OH HO
CH3
H3C
Triple-ringed [14]arene (TRA[14])
Runs 2 - 4
Soluble oligomers and polymers
Scheme 1. Condensation reaction of various phenols with
m-benzenedicarbaldehyde.
Recently, we have succeeded in the synthesis of a ladder-
type cyclic oligomer, noria (water wheel in Latin), through
DCC-based condensation reaction of resorcinol and 1,5-penta-
nedial, using a feed ratio of resorcinol:1,5-pentanedial = 4:1 in
the presence of HCl as a catalyst in ethanol at 80 °C for 48 h.11
Similar condensation reactions of 1,5-pentanedial with other
phenols, 2-methylresorcinol, pyrogallol, and 3-alkoxyphenol,
selectively afforded corresponding noria-like three-dimensional
cage structures.12,13 Thus, we considered that DCC-type con-
densation reactions of phenols and dialdehydes in other
combinations, under appropriate reaction conditions, might also
generate other unique nanostructures. In this paper, we present
the results of a detailed examination of the DCC-type con-
densation reactions of m-benzenedicarbaldehyde with resorcinol,
2-methylresorcinol, p-cresol, and p-tert-butylphenol.
a) 2-Methylresorcinol
b) Resorcinol
c) p-Cresol
These condensation reactions were carried out in n-propanol
at 90 °C in the presence of HCl as a catalyst (Scheme 1). The
phenols and m-benzenedicarbaldehyde have two and four
condensation points, respectively, i.e., this system is an
A2 + B4 type condensation reaction. Oligomers and polymers
were obtained in all cases, and no gel product was formed.
Figure 1 depicts the size exclusion chromatography (SEC)
profiles of these oligomers and polymers. The results are
summarized in Table 1.
d) p-tert-Butylphenol
20
25
30
35
40
Elution time/min
In the case of 2-methylresorcinol, the SEC profile showed
a unimodal peak and the value of molecular dispersity ratio
Figure 1. SEC profiles of the condensation reaction of various
phenols with m-benzenedicarbaldehyde.
Chem. Lett. 2012, 41, 699-701
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

700
CHe3
OHf
CHh3
OHg
CHe3
OHd
Table 1. Condensation reaction of various phenols with m-
benzenedicarbaldehydea
bH3C
aHO
CHb3
OHc
k
OHd
OHg
OHf
OHc
OHa
H2O
m
m
k
i
i
j
l
n
n
l
Run
Phenols
Mn (Mw/Mn)
j
o
s
s
o
o
s
s
p
j
q
q
p
r
l
t
r
t
1
2
3
4
2-Methylresorcinol
Resorcinol
p-Cresol
1750 (1.02)
1500 (1.20)
990 (2.75)
1730 (3.73)
Unimodal
o
j
l
Multimodal
Multimodal
Multimodal
i
m
m
k
k
i
aHO
bH3C
OHa
d OHc
CHb3
OH
OHd
OHg
OHf
OHc
OHf
OHg
b, e, and h
DMSO
p-tert-Butylphenol
CHe3
CHh3
CHe3
Triple-ringed [14]arene (TRA[14])
aThese condensation reactions of various phenols with m-
benzenedicarbaldehyde were carried out using HCl as a
catalyst in n-propanol as a solvent at 90 °C for 48 h.
i and j
g
c
m
k
l
a
f
s
pq
t
n
o
r
d
TMS
0
[M+Na]+ = 1656.59
ppm
10.0 9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
-1.0
(600 MHz, DMSO-d6, TMS)
Figure 3. 1H NMR spectrum of triple-ringed [14]arene
(TRA[14]).
TRA[14]
2-Methylresorcinol
48 h
12 h
5 h
1000
1500
2000
m / z
2500
3000
Figure 2. MALDI-TOF mass spectrum of triple-ringed
[14]arene (TRA[14]).
1 h
(Mw/Mn) was very narrow: 1.02 (Figure 1a). The soluble
oligomers obtained in the case of resorcinol, p-cresol, and
p-tert-butylphenol showed multimodal peaks with Mn = 1500,
990, and 1730, and Mw/Mn = 1.20, 2.75, and 3.73, respectively
(Figures 1b, 1c, and 1d). It seems that these condensation
reactions proceeded according to a DCC mechanism, affording
soluble oligomers. However, it was difficult to separate the
products and confirm their structures. In the case of 2-methyl-
resorcinol, oligomer was obtained by pouring the reaction
mixture into a large amount of n-propanol. Its structure was
examined by 1H NMR, 13C NMR, and MALDI-TOF mass
spectrometry, besides elementary analysis. MALDI-TOF mass
spectrum of this product doped with Na+ ion showed a parent
ion signal at m/z 1656.59 (Figure 2), which corresponds to the
mass of a cyclic oligomer formed by the condensation reaction
of ten equivalents of 2-methylresorcinol with four equivalents of
30 min
5 min
20
25
30
35
40
45
50
Elution time/min
Figure 4. Time-course of SEC profiles during the condensa-
tion reaction of 2-methylresorcinol with m-benzenedicarbalde-
hyde.
groups, as shown in Scheme 1. We named this product triple-
ringed [14]arene (TRA[14]) (yield: 52%).
1
m-benzenedicarbaldehyde. Furthermore, the H NMR spectrum
showed five singlet signals at 8.41, 7.63, 7.58, 7.41, and
7.15 ppm assignable to hydroxy protons, nine signals at 7.19,
6.88, 6.70, 6.66, 6.30, 6.16, 6.00, 5.54, and 5.21 ppm assignable
to aromatic protons, two singlet signals at 5.95 and 5.86 ppm
assignable to methine protons, and three singlet signals at 2.20,
1.92, and 1.84 ppm assignable to methyl protons, respectively
(Figure 3). Its 13C NMR spectrum (SI; Figure S214) and ele-
mental analysis data also supported the corresponding struc-
tures.14 These results strongly indicate that the condensation
reaction of 2-methylresorcinol with m-benzenedicarbaldehyde
afforded a unique cyclic oligomer with a symmetric three-ringed
structure having 20 pendant hydroxy groups and 10 methyl
Next, we examined the effect of reaction time on the
condensation reaction leading to TRA[14] by means of SEC.
Figure 4 shows the time course of SEC profiles of the products
formed by condensation reaction of 2-methylresorcinol with
m-benzenedicarbaldehyde. Initially, polymer and oligomer were
produced, and then these products were converted to TRA[14]
with increasing reaction time. This result confirms that the
reaction proceeded according to a DCC mechanism to give the
most thermodynamically stable compound, TRA[14], selectively.
We have already reported that noria derivatives with
pendant acid-labile groups such as tert-butoxycarbonyl,15 tert-
butyl ester,16 cyclohexyl acetal,17 and adamantyl ester groups,18
Chem. Lett. 2012, 41, 699-701
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

701
and polymerizable groups such as oxetanyl,19 vinyl ether, and
methacryloyl groups20 are candidates for high-performance
photofunctional materials, such as photoresists and UV-curing
materials. Therefore, the solubility and thermal stability of
TRA[14] were examined. TRA[14] was soluble in common
organic solvents such as dimethyl sulfoxide, N,N-dimethylform-
amide, N,N-dimethylacetamide, methanol, acetone, and tetra-
hydrofuran. The temperature of 5 wt % loss (Td5%) of TRA[14],
measured by thermogravimetric analysis, was 340 °C. Thus,
TRA[14] has better solubility and higher thermal stability than
noria. Therefore, TRA[14] derivatives appear to be promising
candidates for application as photofunctional materials.
In summary, we examined the condensation reaction of
several phenols (resorcinol, 2-methylresorcinol, p-cresol, and
p-tert-butylphenol) as A2-type monomers with m-benzenedicar-
baldehyde as a B4-type monomer in n-propanol as a solvent
using HCl as a catalyst at 90 °C for 48 h. In the case of the
combination of 2-methylresorcinol and m-benzenedicarbalde-
hyde, the reaction proceeded according to a DCC mechanism,
selectively affording an oligomer. Its structure was investigated
by 1H NMR, 13C NMR, and MALDI-TOF mass spectrometry,
besides elementary analysis, and it was shown to be a triple-
ringed [14]arene (TRA[14]). TRA[14] showed good solubility
and high thermal stability, and its derivatives with pendant
photoreactive groups are expected to be promising candidates as
novel photoresists or UV-curing materials.
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³
Deceased December 26, 2011.
³³ Present address: Department of Chemistry and Materials
Engineering, Faculty of Chemistry, Materials and Bioengi-
neering, Kansai University, 3-3-35 Yamate-cho, Suita,
Osaka 564-8680
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Chem. Lett. 2012, 41, 699-701
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/