Supramolecular catalysis of esterification by hemicucurbiturils under mild conditions

Article abstract of DOI:10.1016/j.molcata.2012.09.002

Hemicucurbit[6]uril (HemiQ[6])-induced esterification of acids with CH ₃OH was investigated. Esterification of the model substrate MA in the presence of different amounts of HemiQ[6] had reaction rate constants of k _0.5 = 0.18 h^-1, k_1.0 = 0.36 h^-1 and k_2.0 = 0.52 h^-1. These results confirm that the reaction rate increases with the ratio of catalyst to substrate. Ineffective catalysis of MA esterification with a stoichiometric amount of MeOH suggests that the mechanism for HemiQ[6]-catalyzed esterification is solvolysis. Comparing the HemiQ[6]-catalytic kinetics of MA (4-methoxy-4-oxobut-2-enoic acid) with AA (acrylic acid) and BA (benzoic acid) shows that the catalytic activities should bear relation to the size of substrates. The different conversion of sorts of substrates in the presence of HemiQ[6] reveals that the supramolecular catalysis is favor in the conjugated structures. The inefficacy of HemiQ[12] demonstrates that the catalytic capability depends on the structure of the macrocyclic compound used.

Full text of DOI:10.1016/j.molcata.2012.09.002

Journal of Molecular Catalysis A: Chemical 365 (2012) 181–185
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Supramolecular catalysis of esterification by hemicucurbiturils under mild
conditions
Hang Conga,b, Takehiko Yamatoa,∗, Xing Fenga, Zhu Taob
a Department of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga-shi, Saga 840-8502, Japan
b Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 June 2012
Received in revised form 24 August 2012
Accepted 2 September 2012
Available online 7 September 2012
Hemicucurbit[6]uril (HemiQ[6])-induced esterification of acids with CH3OH was investigated. Esterifi-
cation of the model substrate MA in the presence of different amounts of HemiQ[6] had reaction rate
constants of k0.5 = 0.18 h−1, k1.0 = 0.36 h−1 and k2.0 = 0.52 h−1. These results confirm that the reaction rate
increases with the ratio of catalyst to substrate. Ineffective catalysis of MA esterification with a stoichio-
metric amount of MeOH suggests that the mechanism for HemiQ[6]-catalyzed esterification is solvolysis.
Comparing the HemiQ[6]-catalytic kinetics of MA (4-methoxy-4-oxobut-2-enoic acid) with AA (acrylic
acid) and BA (benzoic acid) shows that the catalytic activities should bear relation to the size of substrates.
The different conversion of sorts of substrates in the presence of HemiQ[6] reveals that the supramolec-
ular catalysis is favor in the conjugated structures. The inefficacy of HemiQ[12] demonstrates that the
catalytic capability depends on the structure of the macrocyclic compound used.
Keywords:
Cucurbituril
Supramolecular catalysis
Esterification
Macrocyclic compound
Kinetics
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
by Q[8] has also been developed [15,16]. Other organic reactions
catalyzed via encapsulation include Knoevenagel condensation of
Cucurbituril family (cucurbit[n]urils, Q[n], n = 5–8 or 10) [1–3]
members are important synthetic hosts in the field of supramolec-
ular chemistry and afford facilities for capture of substrates within
the nanospace cavity [4], as in the supramolecular capsules of clas-
sic macrocyclic compounds such as cyclodextrin [5] and calixarene
[6]. Cucurbituril chemistry started with the identification of cucur-
bit[6]uril in the 1980s [7] and other members of this family in 2000
[8], but it is well known that only Q[7] has acceptable solubility
in aqueous solution and none of the family members can dissolve
in any organic solvent. This disadvantage prompted the modifica-
tion of cucurbiturils to improve their solubility in water [9–11] and
led to the identification of hemicucurbiturils (Scheme 1, HemiQ[n],
n = 6 or 12) [12], which can be dissolved in CHCl3 and methanol.
Thus, cucurbituril applications can now be investigated in common
organic solvents.
The unique properties of host–guest complexes prompted
investigation of potential applications of cucurbiturils. The first
study reported was supramolecular catalysis of [3 + 2] cycload-
dition reaction in pioneering work by Mock [13]. Q[6]-catalytic
1,3-dipole addition has contributed to the synthesis of a few
pseudo-polyrotaxanes with a Q[6] block [14]. Photochemical
dimerization of olefins and coumarins via stereoselective catalysis
benzaldehyde with diethyl malonate in ionic liquids [17] and IBX
oxidation of alcohols in aqueous solution [18,19]. Carbocations sta-
bilized by a dipole interaction with the carbonyl groups at the edge
of cucurbiturils [20] have been successfully utilized for acceleration
of oxime hydrolysis [21] and solvolysis of benzoyl chlorides [22] in
the presence of Q[7]. These results prompted us to investigate if
reactions including carbocation intermediates could be catalyzed
by HemiQs in organic solvent, such as esterification between acids
and alcohols (Scheme 1).
Esterification is a classic and fundamental reaction in organic
chemistry and biological systems and is catalyzed by acids [23],
metal coordination complexes [24] or lipases [25]. Esterification is
particularly relevant to biodiesel synthesis in efforts to overcome
the scarcity of traditional fossil energy resources and to mitigate
greenhouse gas emissions [26]. The reaction is also used in the
synthesis of various intermediates and final products for different
purposes [27,28]. To gain an understanding of hemicucurbituril-
induced esterification, sorts of acids were used as substrates
including aryl acids, allyl acids and alkyl acids (Scheme 1).
2. Experimental
2.1. Materials and apparatus
∗
HemiQ[n] (n = 6 or 12) samples were prepared and puri-
fied according to a method in the literature [12] and were
Corresponding author. Tel.: +81 952288679; fax: +81 952288548.
E-mail addresses: yamatot@cc.saga-u.ac.jp (T. Yamato), ecnuc@163.com (Z. Tao).
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.09.002

182
H. Cong et al. / Journal of Molecular Catalysis A: Chemical 365 (2012) 181–185
Scheme 1. Structures of the acids and hemicucurbit[n]uril, n = 6 or 12.
characterized by 1H NMR. HemiQ[6] (CDCl3, ı): 3.40 (s, 24H),
4.67 ppm (s, 12H); HemiQ[12] (CDCl3, ı): 3.36 (s, 24H), 4.67 ppm
(s, 12H). The acids were obtained commercially (Tokyo Kasei Kogyo
Co., Ltd.) and used without further purification.
groups on the portals. However, we observed no change in chem-
ical shift in 1H NMR spectra of a mixture of MA and HemiQ[6]
(Fig. 1c) compared to spectra of the free guest (Fig. 1b) and the
macrocyclic compound (Fig. 1a). Fig. 1d reveals broadening of the
resonance signals for HemiQ[6] after the mixture was heated. This
can be explained as follows. The flexible structure of the host is
frozen and includes various confirmations of the 2-imidzolidinone
units and methylene bridges. The host–guest interaction is also
confirmed by the prominent change of IR absorption of the car-
bonyl groups on binding HemiQ[6] (Supporting Information, Fig.
S5). MA esterification occurred spontaneously, with conversion of
34.7%, and complete conversion was achieved by heating for ∼10 h.
The macrocyclic compound unit was also applied for the screening
of the catalysis, but MA cannot be esterified in the presence of 2-
imidazolidinone in a ratio of 1:6. It could be speculated from the
result that the cavity of HemiQ[6] is the catalytic residence of the
esterification.
1H NMR spectra were recorded at 25 ◦C on a JEOL JNM-Al00
spectrometer in a mixture of CDCl3 and CD3OD. High perfor-
mance liquid chromatography (HPLC) was performed using a JASCO
with a UV detector. The acids and corresponding esters were suc-
cessfully separated by a Wakosil 5SIL chromatographic column
(250 mm × 4.6 mm).
2.2. Catalytic esterification experiments
In the cases of MA, AA, BA, PA (propanoic acid) and ACA (1-
adamantanecarboxylic acid), acids (0.01 mmol) were added to a
mixture of CDCl3 and CD3OD (1:1, 0.6 ml) and the solution was
transferred into an NMR tube. HemiQ[n] (n = 6 or 12) was added
to the acid solution at a corresponding ratio. The NMR tube was
directly heated to 60 ◦C and monitored by 1H NMR over time. Reac-
tant conversion was directly confirmed by 1H NMR spectral data.
For the other substrates, acids (0.01 mmol) were added to a mixture
of CHCl3 and CH3OH (1:1, 1.0 ml) and HemiQ[6] was added to the
solution in a ratio of 1:1. The solution was heated to 60 ◦C, and then
it was diluted with ethyl acetate to an appropriate concentration
for the measure by HPLC.
Kinetic plots of the catalytic esterification of MA in the presence
of different amounts of HemiQ[6] are shown in Fig. 2. As expected,
the esterification rate increased with the amount of HemiQ[6]. The
kinetics of HemiQ[6]-catalyzed esterification can be described by a
pseudo-first-order formula [26]:
Ct = C0 × [1 − exp(−kn × t)],
(1)
where C0 is the initial MA concentration and Ct is the MA concen-
tration at time t, k is the corresponding reaction rate constant, and
the subscript n represents the ratio of MA to HemiQ[6].
3. Results and discussion
The kinetic constants calculated suggest that supramolecular
catalysis greatly depends on the ratio of MA to HemiQ[6]. Addi-
tion of 0.005 mmol of catalyst led to esterification with a reaction
rate constant of 0.18 h−1 (k0.5). Addition of double this amount to
MA is the direct product of the alcoholysis reaction of maleic
anhydride in methanol, but second-order alcoholysis cannot occur
spontaneously and requires a catalyst such as another organic acid.
In the 1H NMR spectrum of MA (Fig. 1b), the resonances at ı 6.29
and 6.30 ppm can be attributed to protons on the olefin of MA, and
the proton resonance of the OCH3 group appears at ı 3.79 ppm.
In general, there are obvious differences in chemical shift patterns
between Qs-bound and free guests due to the shielding effect of
the macrocyclic cavity and the deshielding effect of the carbonyl
yield a HemiQ[6]/MA ratio of 1:1 led to a constant of k1.0 = 0.36 h−1
,
which is double the value for k0.5. A further increase in the amount
of HemiQ[6] in the reaction system improved the percentage con-
version of the substrate and a kinetic constant of k2.0 = 0.52 h−1
was obtained, with a curve fitting observed for HemiQ[6]-catalyzed
esterification kinetics (Fig. 2).

H. Cong et al. / Journal of Molecular Catalysis A: Chemical 365 (2012) 181–185
183
Table 1
HemiQ[6]-catalytic esterification of acids with methanol.
Entries Substrates Time (h)
Conversiona (%)
1
12
84.0
90.7
2
12
3
4
24
24
13.1
58.8
5
6
12
18
86.9
70.8
Fig. 1. 1H NMR spectra of the esterification of MA in the presence of HemiQ[6].
Spectra of (a) HemiQ[6], (b) MA, (c) a mixture of MA and HemiQ[6] in a ratio of 1:1
in CDCl3/CD3OD (1:1) and (d) after the mixture was heated at 60 ◦C. The conversion
was confirmed by comparing the integrated proton resonances for the olefin in MA
(ı 6.29, 6.30 ppm) with those for the product, dimethyl maleate (ı 6.31 ppm).
7
8
24
24
–
–
For the smaller substrate acrylic acid (AA), the HemiQ[6]-
catalytic esterification with CD3OD is also observed. There is no
any change of the proton chemical shift of AA in the presence
of HemiQ[6] in a 1:1 ratio to be observed, and only the broad-
ened resonance peak of HemiQ[6] (Fig. 3) represents the host–guest
interaction as same as the case of MA. The conversion of AA at the
a
The conversion of entries 1–6 was measured by HPLC, and the esterification of
entries 7 and 8 were traced by 1H NMR.
different time could be non-linear fitted to give a kinetic constant of
kAA = 1.22 h−1 with the formula (1) (Fig. 3, insert), which is almost
4 folds of the k1.0 in the MA system, so the HemiQ[6]-mediated
esterification of AA is obviously faster than the MA.
BA was also used to investigate the catalytic activity of HemiQ[6]
in the esterification system. 1H NMR spectra for BA (Fig. 4a) and a
mixture of BA and HemiQ[6] (Fig. 4b) reveals no obvious changes in
resonance signal for protons on the aryl ring. However, heating of
the BA and HemiQ[6] solution induced broadening of the resonance
peaks (Fig. 4c), reflecting interaction between BA and HemiQ[6].
1H NMR monitoring of conversion revealed that supramolecular
catalysis was still effective for BA esterification at a HemiQ[6]/BA
ratio of 1:1, but the reaction was much slower than for HemiQ[6]-
catalyzed MA esterification. The conversion of only 45.2% after 5 h
is less than two-thirds of that in the MA system. Over the next 5 h,
conversion improved by ∼13%, but the further 4% improvement
Fig. 2. Kinetic plots of MA esterification catalyzed by different ratios of HemiQ[6].

184
H. Cong et al. / Journal of Molecular Catalysis A: Chemical 365 (2012) 181–185
Fig. 3. 1H NMR spectra of the esterification of AA in the presence of HemiQ[6]. Spectra of (a) AA, (b) AA and HemiQ[6] in a ratio of 1:1 in CDCl3/CD3OD (1:1) and (c) after
the mixture was heated at 60 ◦C. The conversion was confirmed by comparing the integrated proton resonances for the acrylic group in AA (ı 6.43 ppm) with those for the
product, methyl benzoate (ı 6.41 ppm). Insert: kinetic plots of AA esterification in the presence of HemiQ[6] in the ratio of 1:1.
in conversion at 15 h indicates that esterification was close to the
point of chemical equilibrium. The above kinetic plots have been
collected in the insert of Fig. 4 to be curve fitted with the kinetic con-
stant kBA = 0.19 h−1, which is almost half of that in the esterification
presence of equivalent HemiQ[6] in the mixture of CHCl3 and
CH3OH. As shown in Table 1, the results suggest that the catalytic
activities should prefer the conjugated structure. Two alkyl acids,
PA and ACA, were subjected to the same catalytic esterification, but
no reaction occurred. These negative results confirm that catalysis
depends on the substrate structure, and is favored for aryl and allyl
substrates. However, there are some different catalytic activities of
HemiQ[6] on the esterification of substituted benzoic acid, which
tends to prove that the electronic effect and steric effect of the sub-
strates seem to exist for these aryl acid systems. Almost all of the
aryl acids (Entries 1, 2, and 4–6) can be converted to the corre-
sponding esters with very satisfying conversion in the presence of
HemiQ[6], but only 13.1% conversion in the case of SA (Entry 3)
of MA and the one tenth of kAA
.
These results demonstrate that effective esterification largely
depends on the substrate structure. The aryl ring of BA is larger than
the substituent of MA and AA, and therefore it make against the cat-
alytic esterification by this macrocyclic compound. However, the
esterification of the smallest substrate AA can be preformed more
easily than the others.
Further studies for the purpose of the universality and selectiv-
ity of this supramolecular catalysis have been carried out in the
Fig. 4. 1H NMR spectra of the esterification of BA in the presence of HemiQ[6]. Spectra of (a) BA, (b) BA and HemiQ[6] in a ratio of 1:1 in CDCl3/CD3OD (1:1) and (c) after
the mixture was heated at 60 ◦C. The conversion was confirmed by comparing the integrated proton resonances for the benzyl group in BA (ı 7.45 ppm) with those for the
product, methyl benzoate (ı 7.38 ppm). Insert: kinetic plots of BA esterification in the presence of HemiQ[6] in the ratio of 1:1.

H. Cong et al. / Journal of Molecular Catalysis A: Chemical 365 (2012) 181–185
185
can be found. The result indicates that the inductive effect of o-
OH group should be disadvantage of the esterification, because it
is not able to stabilize the carbon cation intermediate in the course
of the formation of ester. On the other hand, the conversions of
both o-ABA (o-aminobenzoic acid) (Entry 1) and SA (salicylic acid)
(Entry 3) are less than that of the p-substituted substrates, p-ABA (p-
aminobenzoic acid) (Entry 2) and p-HBA (p-hydroxybenzoic acid)
(Entry 4), which denotes the existence of the steric effect in this
supramolecular catalysis.
International Collaboration Project of Guizhou Province (Grant
No. [2011]7003), and the Natural Science Foundation of Guizhou
Province (Grant No. [2008]75).
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.molcata.
2012.09.002.
For a random selection, four substrates, MA, BA, ACA and PA,
were subjected to esterification with a stoichiometric amount of
MeOH in the presence of HemiQ[6] in CDCl3, but no ester prod-
uct was synthesized in more than 24 h. These results indicate that
the catalytic activity of HemiQ[6] greatly depends on the substrate
concentration and suggest that the mechanism for esterification is
a solvolytic reaction between the acids and the CH3OH solvent.
To understand the dependence of supramolecular catalysis on
the structure of the macrocyclic catalyst, HemiQ[12] was used as
an alternative to catalyze acid esterification in CDCl3/CD3OD (1:1)
solution. Only resonance broadening was observed for HemiQ[12]
singlets in 1H NMR spectra of a heated mixture of BA and HemiQ[12]
(Supporting Information, Fig. S4), and supramolecular catalysis was
ineffective for esterification of the four acids. Thus, a more flexible
structure and a larger cavity, as in HemiQ[12], are negative factors
in this catalytic esterification.
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4. Conclusion
We developed a method for effective supramolecular hemicu-
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HemiQ[6]-induced esterification depends on the amount of
HemiQ[6], and a greater amount of catalyst should increase the
reaction rate. The electronic and steric structures of the substrates
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