Imidazol(in)ium-2-carboxylates as latent, thermally activated organocatalysts for transesterification reactions

Article abstract of DOI:10.1016/S1872-2067(11)60353-7

1,3-Disubstituted imidazol(in)ium-2-carboxylates (ImCO₂) were used as precatalysts for transesterification reactions of unactivated ethyl benzoate with monohydric alcohols, dihydric alcohols, and amino alcohols. Highly active N-heterocyclic carbenes (NHCs) are usually not used directly as catalysts because of their air and moisture sensitivity. Here they were liberated in situ by thermal decarboxylation of ImCO₂ at designated temperatures. The results showed that the yield of the reactions reached up to 95 within 3 h using only 0.5 mol catalyst. No active enol esters, molecular sieves, or a 20-fold excess of alcohol were used to drive the reaction to completion. It was proved that unsaturated imidazolium-2-carboxylates have a better activity than saturated species in this type of reaction. Different types of substituting groups of ImCO₂ exhibited varied transesterification activity.

Full text of DOI:10.1016/S1872-2067(11)60353-7

CHINESE JOURNAL OF CATALYSIS
Volume 33, Issue 3, 2012
Online English edition of the Chinese language journal
Cite this article as: Chin. J. Catal., 2012, 33: 502–507.
ARTICLE
Imidazol(in)ium-2-carboxylates as Latent, Thermally
Activated Organocatalysts for Transesterification Reactions
1
,2
1,
WANG Yanqin , LI Zhenjiang *
1
State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Uni-
versity of Technology, Nanjing 210009, Jiangsu, China
2
College of Science, Nanjing Forestry University, Nanjing 210037, Jiangsu, China
2
Abstract: 1,3-Disubstituted imidazol(in)ium-2-carboxylates (ImCO ) were used as precatalysts for transesterification reactions of unac-
tivated ethyl benzoate with monohydric alcohols, dihydric alcohols, and amino alcohols. Highly active N-heterocyclic carbenes (NHCs) are
usually not used directly as catalysts because of their air and moisture sensitivity. Here they were liberated in situ by thermal decarboxy-
2
lation of ImCO at designated temperatures. The results showed that the yield of the reactions reached up to 95% within 3 h using only 0.5
mol% catalyst. No active enol esters, molecular sieves, or a 20-fold excess of alcohol were used to drive the reaction to completion. It was
proved that unsaturated imidazolium-2-carboxylates have a better activity than saturated species in this type of reaction. Different types of
substituting groups of ImCO
2
exhibited varied transesterification activity.
Key words: N-heterocyclic carbene; organocatalyst; imidazol(in)ium-2-carboxylate; transesterification; unactivated ethyl benzoate
Serving both as a key intermediate and as a protecting
group in organic transformations, the ester/acyl moiety is an
important functional group in polymers, drugs, and biologi-
cally relevant compounds [1]. In addition, the ester unit has
been found ubiquitous industrial applications as a building
block for transformations such as polymerization (ring open-
ing of lactones), polycondensation, or macrolactonization
reactions [2].
as efficient transesterification reaction catalysts. The utilization
of NHCs was complicated by their air- and moisture-sensitivity
that necessitated the use of stable carbene precursors to gen-
erate free NHCs in situ. Imidazolium precursor salts were
commonly used from which NHCs were generated by adding
potassium tert-butoxide in tetrahydrofuran (Scheme 1) [10–14].
However, this method requires two reaction steps and is re-
stricted to base-tolerant substrates.
Transesterification is one of the major means of preparation
of esters. The choice of catalyst is important for an effective
transesterification reaction. Although organometallic catalysts
A few other strategies have thus been developed to facilitate
their handling and to generate NHCs in situ without the need
for a strong base. For instance, the thermal activation of
2-alkoxy [15], trichloromethyl [16] or pentafluorophenyl ad-
ducts [17] of NHCs generated free carbenes more conveniently
[
3,4] or strongly basic catalysts such as sodium hydride and
potassium tert-butoxide [5] have been employed, they either
were limited to acid-insensitive substrates or required high
catalyst loading and long reaction times.
R
R
The versatile nucleophilic organic catalysts known as
N-heterocyclic carbenes (NHCs) [6] have been shown to ef-
fectively mediate organic transformations due to their unique
electronic and steric properties [7–9]. In 2002, Grasa et al. [10]
and Nyce et al. [11] simultaneously reported the use of NHCs
N
tBuOK
N
KCl
Cl
THF
N
R
N
R
Scheme 1. Procedure for the generation of free NHCs in situ.
Received 10 September 2011. Accepted 10 December 2011.
*
Corresponding author. Tel/Fax: +86-25-83172083; E-mail: zjli@njut.edu.cn
This work was supported by the Major Science and Technology Research Program of Ministry of Education of China (208049) and the National Basic Research
Program of China (973 Program, 2009CB724700).
Copyright © 2012, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(11)60353-7

WANG Yanqin et al. / Chinese Journal of Catalysis, 2012, 33: 502–507
R
N H
R
N
R1
1
2
R , R = 2,6-i-PrC H
IPrCO , 1a
6
3
2
X-H
N
N
O
O
1
2
R , R = 2,4,6-MeC H
IMesCO , 1b
6
3
2
X
ꢀ
X = CCl , C F , RO
3 6 5
o
1
2
6
0 120 C
N
R
N
R
R = Me, R = Et
EMimCO , 1c
2
R2
R1
1
2
R , R = Bu
BBimCO , 1d
2
Scheme 2. Chloroform, pentafluorobenzene, and alcohol adducts of
1
2
R , R = 2,6-i-PrC H
SIPrCO , 1e
6
3
2
carbenes.
N
N
O
O
1
2
R , R =2,4,6-MeC H
SIMesCO , 1f
6
3
2
(
Scheme 2). However, the chloroform, pentafluorobenzene,
R2
and alcohols released from adducts remain in the reaction
system and may potentially interfere with the transesterifica-
tion reaction. Therefore, obtaining a reaction environment with
simple NHCs only is difficult. Moreover, these methodologies
cannot be applied to generate imidazol-2-ylidenes (unsaturated
NHCs).
2
Scheme 4. A series of ImCO prepared in this article.
1
13
H NMR and C NMR spectra were recorded at 300 and
125.5 MHz, respectively, in d-CHCl on a Bruker DRX500
spectrometer. Chemical shifts were expressed in parts per
million (ppm) using TMS as internal standard for H NMR and
3
1
In contrast to the aforementioned 2-adducts of NHCs, imi-
dazol(in)ium-2-carboxylates (ImCO ) are readily formed by
1
3
2
for C NMR spectra.
reactions of virtually all types of NHCs with CO [18]. The
2
ImCO readily lose their CO moiety upon heating or dissolu-
1.1 Transesterification of ethyl benzoate with monohydric
alcohol
2
2
tion and have been extensively used as NHCs transfer agents in
organometallic chemistry for the synthesis of NHC metal
complexes [19,20]. Moreover, they were used occasionally as
latent organic (pre)catalysts in organic [21–23] and polymer
chemistry [24–26].
Catalyst 1 (0.5 mol%) was added to a mixture of ethyl ben-
zoate (3.0 g, 20 mmol) and benzyl alcohol (3a, 5.5 g, 50 mmol)
under argon atmosphere and magnetic stirring. The mixture
was processed continuously for 3 h at 120 ºC in an oil bath. The
resulting mixture was cooled and purified by column chro-
matography using an ethyl acetate/hexane (V/V = 20:1) mixture
to yield benzyl benzoate (4a, Scheme 5). 4a: colorless liquid.
In this article, we describe the transesterification between
the unactivated ethyl benzoate and monohydric alcohols, di-
hydric alcohols, and amino alcohols utilizing ImCO as pre-
2
catalysts. The free and pure NHCs were liberated in situ by
1
thermal decarboxylation of the ImCO with carbon dioxide
H NMR: ꢀ 5.36 (s, 2H), 7.40–7.56 (m, 8H), 8.03 (d, J = 8.4 Hz,
2
1
3
eliminating spontaneously at designated temperatures (Scheme
2H). C NMR: ꢀ 66.7, 128.1, 128.2, 128.3, 128.6, 129.7, 130.1,
3
).
132.9, 136.1, 166.4.
1
-Phenylethyl benzoate (4b) was prepared from ethyl ben-
1
Experimental
zoate and 1-phenylethanol (3b) using the same procedure. 4b:
1
colorless liquid. H NMR: ꢀ 1.62 (d, J = 8.4 Hz, 3H), 5.40 (m,
1
3
All starting materials and reagents were obtained from
1H), 7.38–7.56 (m, 8H), 8.05 (d, J = 8.4 Hz, 2H). C NMR: ꢀ
19.5, 72.1, 127.1, 127.6, 128.6, 128.9, 129.9, 130.1, 133.0,
141.8, 165.9.
commercial sources and used as received unless otherwise
noted. All reactions were performed under an argon atmos-
phere using standard Schlenk techniques. All glassware was
dried overnight prior to use. Ethyl benzoate and benzyl alcohol
Cyclohexyl benzoate (4c) was prepared from ethyl benzoate
and cyclohexanol (3c) using the same procedure. 4c: colorless
1
were refluxed over calcium hydride (CaH ) overnight and then
liquid. H NMR: ꢀ 1.49 (m, 2H), 1.53 (m, 4H), 1.99 (m, 4H),
2
distilled from CaH . Flash chromatography was performed on
silica gel using ethyl acetate/hexane or dichlor-
methane/methanol mixtures.
2
O
O
ꢀ
3a 3c, 0.5 mol% 1
O
O
4a
4b
O
o
Ar, 120 C, 3 h
N,Nꢀ-disubstituted ImCO (1a–1f, Scheme 4) were prepared
according to the literature [27–31].
2
O
OH
OH
3
a
R1
N
R1
N
O
O
CO2
3b
3c
O
4
c
decarboxylation
OH
N
O
N
R2
R2
1
2
Scheme 5. Reaction of ethyl benzoate with monohydric alcohol cata-
lyzed by ImCO
Scheme 3. The decarboxylation of ImCO
2
.
2
.

WANG Yanqin et al. / Chinese Journal of Catalysis, 2012, 33: 502–507
1
3
3
.91 (m, 1H), 7.56–7.65 (m, 4H), 8.07 (d, J = 8.4 Hz, 1H).
C
1.3 Transesterification of ethyl benzoate with amino
alcohol
NMR: ꢀ 24.1, 25.7, 31.1, 70.6, 128.6, 129.9, 130.1, 133.0,
1
65.9.
Catalyst 1 (0.5 mol%) was added to a mixture of ethyl
benzoate (5a, 3.0 g, 20 mmol) and ethanolamine (1.8 g, 30
mmol) under argon atmosphere and magnetic stirring. The
mixture was stirred at 120 ºC for 3 h in an oil bath. The re-
sulting mixture was cooled and purified by column chroma-
tography using a dichloromethane/methanol mixture to yield
N-(2-hydroxyethyl) benzamide (6a, Scheme 7) [34]. 6a: white
1
.2 Transesterification of ethyl benzoate with dihydric
alcohol
Catalyst 1a (0.5 mol%) was added to a mixture of ethyl
benzoate (7.5 g, 50 mmol) and glycol (3d, 1.2 g, 20 mmol)
under argon atmosphere and magnetic stirring. The mixture
was stirred at 120 ºC for 3 h in an oil bath. The resulting mix-
ture was cooled and purified by column chromatography using
an ethyl acetate/hexane mixture to yield 2-hydroxyethyl ben-
zoate (4d, Scheme 6) and ethane-1,2-diyl dibenzoate (4g). 4d:
colorless liquid. H NMR: ꢀ 2.09 (s, 1H), 3.95 (t, J = 4.7 Hz,
2
=
1
solid, m.p. 42–44 ºC. H NMR: ꢀ 2.14 (s, 1H), 3.64 (m, 2H),
3.85 (t, J = 5.0 Hz, 2H), 6.60 (s, 1H), 7.43 (t, J = 7.7 Hz, 2H),
1
3
7.51 (t, J = 7.4 Hz, 1H) , 7.78 (d, J = 7.3 Hz, 2H) . C NMR: ꢀ
42.7, 61.5, 126.9, 128.4, 131.5, 134.0, 168.8.
1
N-(3-hydroxypropyl) benzamide (6b) was prepared from
ethyl benzoate and propanolamine (5b) using the same pro-
H), 4.46 (t, J = 4.7 Hz, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.58 (t, J
1
3
1
7.4 Hz, 1H), 8.06 (d, J = 7.2 Hz, 2H) . C NMR: ꢀ 61.4, 66.7,
cedure. 6b: white solid, m.p. 46–48 ºC. H NMR: ꢀ 1.74 (m,
1
28.4, 129.7, 129.8, 133.2, 166.9. 4g: white solid, m.p. 48–50
2H), 3.21 (s, 1H), 3.40 (s, 1H), 3.52 (q, J = 6.1 Hz, 2H), 3.65 (t,
J = 5.6 Hz, 2H), 7.34 (t, J = 7.7 Hz, 2H), 7.43 (t, J = 7.4 Hz, 1H),
7.73 (d, J = 7.3 Hz, 2H). C NMR: ꢀ 31.8, 37.3, 59.8, 126.9,
1
ºC. H NMR: ꢀ 4.6 (s, 4H), 7.44 (t, J = 7.6 Hz, 4H), 7.56 (t, J =
1
3
13
7.4 Hz, 2H), 8.06 (d, J = 7.1 Hz, 4H). C NMR: ꢀ 62.7, 128.4,
1
29.7, 129.8, 133.1, 166.4.
128.4, 131.4, 134.1, 168.6.
3
-Hydroxypropyl benzoate (4e) and propane-1,3-diyl
(S)-N-(1-hydroxy-3-phenyl-2-propanyl) benzamide (6c)
was prepared from ethyl benzoate and (S)-2-amino-
3-phenyl-1-propanol (5c) using the same procedure. 6c: white
dibenzoate (4h) were prepared from ethyl benzoate and
,3-propanediol using the same procedure. 4e: colorless liquid.
H NMR: ꢀ 1.99 (m, 2H), 2.62 (s, 1H), 3.75(t, J = 6.2 Hz, 2H),
.46 (t, J = 6.2 Hz, 2H), 7.43 (t, J = 7.7 Hz, 2H), 7.55 (t, J = 7.4
Hz, 1H), 8.02 (d, J = 7.3 Hz, 2H). C NMR: ꢀ 31.8, 58.9, 61.8,
1
1
1
solid, m.p. 167–168 ºC. H NMR: ꢀ 2.63 (t, J = 5.2 Hz, 1H),
4
3.01 (d, J = 7.2 Hz, 2H), 3.81 (m, 2H), 4.38 (m, 1H), 6.36 (s,
1
3
13
1H), 7.27–7.51 (m, 8H), 7.67 (d, J = 7.1 Hz, 2H). C NMR: ꢀ
1
28.3, 129.5, 130.0, 133.9, 166.9. 4h: white solid, m.p. 65–67
37.8, 53.4, 64.4, 126.8, 128.6, 128.8, 129.3, 130.1, 131.6, 134.4,
168.0.
1
ºC. H NMR: ꢀ 2.27 (m, 2H), 4.51 (t, J = 6.2 Hz, 4H), 7.42 (t, J
=
7.6 Hz, 4H,), 7.55 (t, J = 7.4 Hz, 2H), 8.05 (d, J = 7.3 Hz, 4H).
C NMR: ꢀ 28.2, 61.7, 128.2, 129.5, 130.0, 132.8, 166.3.
1
3
2 Results and discussion
4
-Hydroxybutyl benzoate (4f) and butane-1,4-diyl dibenzo-
ate (4i) were prepared from ethyl benzoate and 1,4-butanediol
using the same procedure. 4f: colorless liquid. H NMR: ꢀ 1.68
2.1 Transesterification reaction of unactivated ethyl
benzoate with monohydric alcohols
1
(
4
m, 2H), 1.84 (m, 2H), 2.51 (s, 1H), 3.67 (t, J = 6.5 Hz, 2H),
.32 (t, J = 6.6 Hz, 2H), 7.39 (t, J = 7.6 Hz, 2H), 7.51 (t, J = 7.4
The synthesis of benzyl esters has been seldom reported. We
studied the transesterification of benzyl alcohol 3a with unac-
1
3
Hz, 1H), 8.01 (d, J = 7.1 Hz, 2H). C NMR: ꢀ 25.1, 62.0, 64.7,
1
28.2, 129.4, 130.2, 132.8, 166.6. 4i: white solid, m.p. 82–84
tivated ethyl benzoate using the ImCO as an effective
acyl-transfer catalyst. To suppress the reversibility of the
transesterification, enol esters have been always used as acy-
2
1
ºC. H NMR: ꢀ 1.96 (s, 4H), 4.41 (s, 4H), 7.43 (t, J = 7.7 Hz,
4
1
3
H), 7.56 (t, J = 7.4 Hz, 2H), 8.05 (d, J = 7.3 Hz, 4H). C NMR:
ꢀ
25.6, 64.4, 128.3, 129.5, 130.3, 132.9, 166.6.
O
ꢀ
O
O
5
a 5c, 0.5 mol% 1
O
O
OH 6a
OH 6b
o
Ph
Ph
N
H
(
CH2)n
Ar, 120 C, 3 h
OH
O
OH
O
5a H N
ꢀ
n = 2, 4d; n = 3, 4e; n = 4, 4f
2
3
d 3f, 0.5 mol% 1a
O
O
N
H
o
O
5b H N
OH
Ar, 120 C, 3 h
2
(
CH2)n
Ph
OH
O
Ph
3d
HO
HO
O
OH
5
c
3e
OH
OH
n = 2, 4g; n = 3, 4h; n = 4, 4i
H N
2
OH
6c
Ph
N
H
3
f
HO
Scheme 6. Reaction of ethyl benzoate with dihydric alcohols catalyzed
by catalyst 1a.
Scheme 7. Reaction of ethyl benzoate with amino alcohols catalyzed
by ImCO
2
.

WANG Yanqin et al. / Chinese Journal of Catalysis, 2012, 33: 502–507
lation agents [1] and molecular sieves or a 20-fold excess of
O
alcohol [11] have been commonly added to drive the reaction
to completion in earlier studies. Different molar ratios of
benzyl alcohol and unactivated ethyl benzoate were examined
here in the transesterification catalyzed by 0.5 mol% of 1a
R1
R2
R
R1
R2
R'
O
O
N
N
2
N
N
O
R'
O
R''
or
R
O
(
Table 1, entries 1 to 3) at 120 ºC. The results showed that yield
R
acyl-imidazol(in)ium
R''
O
up to 97% was obtained of the reaction between the ethyl
benzoate and the benzyl alcohol when the molar excess of
benzyl alcohol was 2.5 times the amount of ethyl benzoate.
Thus, the amount of alcohol was greatly reduced with respect
to the literature.
Scheme 8. NHCs in the transesterification reaction.
vious reports have shown that the alkyl-substituted NHCs have
relatively strong activity due to their higher nucleophilicity and
smaller steric hindrance [34,35]. The opposite results obtained
here were probably due to that the alkyl-substituted ImCO2
with high activity promoted the reverse reaction simultane-
ously, which lead to the decline of the yield.
We investigated the transesterification of different mono-
hydric alcohols, such as 1-phenylethanol (3b) and cyclohexa-
nol (3c), with ethyl benzoate in the presence of 0.5 mol%
catalyst 1a, which gave high product yield (Table 1, entries 9
The catalytic activity of a series of ImCO catalysts was
2
studied, including IPrCO (1a), IMesCO (1b), EMimCO (1c),
2
2
2
BBimCO (1d), SIPrCO (1e), and SIMesCO (1f). As can be
2
2
2
seen in Table 1, the unsaturated imidazolium-2-carboxylates
1a–1d) were more active than the saturated species (1e and 1f).
They exhibited excellent catalytic activity and yields
85%–97%) in the presence of 2.5 mol% alcohol and 0.5 mol%
(
(
of 1a–1d. However, poor transesterification yields were ob-
tained under the same conditions when the catalysts were
and 10). It proved that the unsaturated ImCO were efficient
organic catalysts for transesterification of unactivated ethyl
benzoate with both primary alcohols and secondary alcohols.
2
changed to the saturated ImCO (1e and 1f, yield = 13% and
2
3
0%, respectively). It was reported by Wanzlick and Kleiner
[
32] that the imidazolidin-2-ylidene was prone to dimerization
2
.2 Transesterification of ethyl benzoate with dihydric
and the dimeric electron-rich olefins were gained. In addition
to the possibility of dimer formation, the different nucleo-
philicity of the saturated and unsaturated carbenes may also
influence the reaction. Saturated NHCs are stronger nucleo-
philes [33] and can easily attract the carbonyl carbon atom of
esters and form acyl-imidazolin intermediates (Scheme 8). The
C–C bond between the saturated carbene and the carbonyl
carbon was stable. This made the release of free carbene dif-
ficult in the next reversible step and the carbene was prevented
from participating in the catalytic cycle of transesterification.
alcohols
The catalytic activity of the ImCO , which was excellent in
the transesterification of unactivated ethyl benzoate with
monohydric alcohols, was investigated by replacing the
monohydric alcohols with dihydric ones in order to test the
range and the generality of the reaction. Three dihydric alco-
hols, i.e. glycol (3d), 1,3-propanediol (3e), and 1,4-butanediol
2
(
3f), were examined at 120 ºC with IPrCO as the catalyst and a
2
2
.5-fold molar excess of ethyl benzoate. Two kinds of products,
Unsaturated ImCO with different substituting groups also
2
monosubstituted and disubstituted, were obtained because of
the two hydroxyl groups of dihydric alcohols.
influenced the efficiency of the transesterification. The corre-
sponding aryl-substituted ImCO , 1a and 1b, gave higher
2
Under the same reaction conditions as before, the yields
improved with increasing carbon chain length in dihydric
alcohols (Table 2). The reason for the yield increase may be
due to the extensibility and flexibility of the carbon chain in
dihydric alcohols, which leads to facile contact with ethyl
benzoate. A monosubstituted product and a disubstituted
product were obtained because with dihydric alcohols two
hydroxide radicals could participate in the transesterification
product yields (Table 1, entries 1 and 4) than the al-
kyl-substituted 1c and 1d (Table 1, entries 5 and 6). All pre-
Table 1 Reaction of ethyl benzoate with monohydric alcohol catalyzed
by ImCO
2
Monohydric
alcohol
3a
n(ethyl benzoate)/
n(alcohol)
1:2.5
Yield
(%)
97
80
65
89
85
85
13
Entry Catalyst
1
2
3
4
5
6
7
8
9
0
1a
1a
1a
1b
1c
1d
1e
1f
3a
3a
3a
3a
3a
3a
3a
3b
1:1.5
1:1
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
Table 2 Reaction of ethyl benzoate with dihydric alcohols catalyzed by
catalyst 1a
Dihydric
alcohol
3d
Selectivity (%)
Entry
Yield (%)
Monosubstituted
Disubstituted
58 (4g)
46 (4h)
1
2
3
41
79
95
42 (4d)
54 (4e)
57 (4f)
30
86
83
3e
3f
1a
1a
43 (4i)
1
3c
1:2.5
Reaction conditions: 0.5 mol% catalyst, ethyl benzoate/dihydric alcohol
molar ratio = 2.5/1, 120 ºC, 3 h.
Reaction conditions: 0.5 mol% catalyst, 120 ºC, 3 h.

WANG Yanqin et al. / Chinese Journal of Catalysis, 2012, 33: 502–507
reaction, respectively. The ratios of monosubstituted and
mine 5b gave the product at 89% yield, while
(S)-2-amino-3-phenyl-1-propanol 5c led to a lower conversion
(possibly due to its steric bulk, Table 3, entries 7 and 8).
disubstituted products were similar when ethyl benzoate re-
acted with any of the three kinds of dihydric alcohols. The
disubstituted product of glycol 4g was gained in 58% yield
(
percentage of the total products) while 4d was obtained at
3 Conclusions
4
1
2% yield. The yield of the monosubstituted products of both
,3-propanediol and 1,4-butanediol were higher than the
The ImCO couldcatalyze efficiently both transesterification
2
disubstituted ones, 54% 4e and 57% 4f, respectively. It can be
assumed from the above results that the yield of monosubsti-
tuted products may increase and the ones the disubstituted
products may decrease when dihydric alcohols with longer
carbon chain were chosen.
and amidation reactions. The application range of this method
was shown to include reactions of unactivated ethyl benzoate
with monohydric alcohols, dihydric alcohols, and amino al-
cohols. The conversions of the reactions were satisfactory
without need to use activated esters, molecular sieves, or a
2
0-fold excess of acohol. The ImCO precatalysts decarboxy-
2
2
.3 Synthesis of amides
lated at a designated temperature to liberate NHCs in situ for
catalysis of the transesterification. Carbon dioxide is elimi-
nated in this process which spontaneously escapes from the
leaving a controlled reaction environment with simple NHCs
behind. The unsaturated imidazolium-2-carboxylates (1a–1d)
displayed a better catalytic activity than the saturated species
(1e and 1f) both in the reactions of benzyl alcohol and etha-
The synthesis of amides is important in many areas of
chemistry, including peptide, polymer, and complex molecule
synthesis. Herein, we report the amidation of unactivated esters
with amino alcohols catalyzed by ImCO . Movassaghi and
Schmidt [36] suggested that the reaction mechanism involves a
carbon-centered Brønsted base nucleophile activation, which
initiates a transesterification. This activation is then followed
by a rapid NꢁO acyl-transfer reaction.
2
nolamine with ethyl benzoate. The alkyl-substituted ImCO (1c
2
and 1d) have a relatively high activity due to their higher nu-
cleophilicity and smaller steric hindrance.
The completion of the catalytic amidation reaction does not
require the use of excess coupling components, molecular
sieves, or activated esters. The catalysts with different structure
listed in Scheme 8 were tested in the amidation reaction of
ethyl benzoate with ethanolamine 5a. This procedure was
carried out at 120 ºC for 3 h in the presence of 0.5 mol% cata-
lyst with ethanolamine in a 1.5-fold excess of ethyl benzoate.
The transesterification equilibria were influenced by the nature
of the nucleophile [2]. The stronger nucleophilic al-
kyl-substituted 1c and 1d performed better (yield = 99% and
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Amide
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