Microwave-promoted direct amidation of unactivated esters catalyzed by heteropolyanion-based ionic liquids under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2015.05.118

Abstract A simple and efficient procedure for the synthesis of amides directly from unactivated esters and amines catalyzed by heteropolyanion-based ionic liquids under microwave-promoted and solvent-free conditions has been reported. The practical protocol was found to be compatible with different structurally diverse substrates. Moderate to excellent yields, solvent-free media, and operational simplicity are the main highlights. Furthermore, the heteropolyanion-based ionic liquids were easily reusable for this amidation.

Full text of DOI:10.1016/j.tetlet.2015.05.118

Tetrahedron Letters 56 (2015) 4527–4531
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave-promoted direct amidation of unactivated esters
catalyzed by heteropolyanion-based ionic liquids under solvent-free
conditions
⇑
⇑
Renzhong Fu, Yang Yang , Yunsheng Ma, Fei Yang, Jingjing Li, Wen Chai, Quan Wang , Rongxin Yuan
Jiangsu Laboratory of Advanced Functional Material, School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu 215500, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple and efficient procedure for the synthesis of amides directly from unactivated esters and amines
catalyzed by heteropolyanion-based ionic liquids under microwave-promoted and solvent-free condi-
tions has been reported. The practical protocol was found to be compatible with different structurally
diverse substrates. Moderate to excellent yields, solvent-free media, and operational simplicity are the
main highlights. Furthermore, the heteropolyanion-based ionic liquids were easily reusable for this
amidation.
Received 20 April 2015
Revised 28 May 2015
Accepted 30 May 2015
Available online 4 June 2015
Keywords:
Amide
Ó 2015 Elsevier Ltd. All rights reserved.
Ester
Ionic liquid
Microwave-promoted
Solvent-free condition
The formation of amide bonds is one of the most common and
important processes for both synthetic organic chemists and biol-
commonly used in the synthesis of amides because harsh condi-
tions, such as high temperature, high pressure, or the use of more
than stoichiometric amounts of strongly basic reagents, are
required. Great efforts have recently been made to avoid this
1
ogists. Amide linkages are present in many biologically active
2
molecules, key natural products, and synthetic polymers. It has
9
–21
been noted recently that about 66% of all preliminary screening
reactions in industrial medicinal chemistry laboratories involve
problem by using activating reagents or catalysts.
alytic systems based on inorganic catalysts (K
Efficient cat-
9
10
3
PO
), organic catalysts (tert-
butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diaza-
4
, NaOMe,
3
11
12
amide formation. Therefore, efficient synthesis of amides is an
Mg(OCH
3
)
2
or CaCl
2
,
3 2
and Mg N
important topic of modern synthetic chemistry not only in aca-
demic research but also in industrial application.4
phosphorine
(BEMP),
13
1,5,7-triazabicyclo[4.4.0]dec-5-ene
1
4
15
17
Traditionally, the reactions of activated carboxylic acid deriva-
tives (such as acids, anhydrides, acyl halides, or esters) with ami-
nes are applied for the synthesis of amides, but there are
limitations, such as harsh reaction conditions, poor atom effi-
ciency, stoichiometric amount of toxic wastes, and difficulties in
(TBD), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and N-hete-
rocyclic carbine ), metallic catalysts (Ru-MACHO, La(OTf)
1
6
18
3
,
1
9
20
Pd(OAc)
2
,
3 2
and DABCO(AlMe ) ), and enzymatic-catalyzed
2
1
transformations have been reported. However, some of these
methods still suffer from certain demerits, such as recycle of cata-
lysts, limited substrate scopes, low selectivities, and long reaction
times. Thus, the development of simple and environmentally
benign but efficient catalysts which can promote direct amidation
of unactivated esters under mild conditions is in high demand.
Over the past few decades, ionic liquids (ILs) have attracted
more and more interests of chemists. Meanwhile, ILs have been
successfully used in organic transformations as efficient and eco-
friendly reaction media and/or catalysts due to their excellent
properties such as negligible vapor pressure, ease of recovery,
5
purification. In addition, labile substrates and limited substrate
scopes are also restricted. Thus, these drawbacks have promoted
the development of a number of catalytic approaches to amide
6
bond formation in recent years. Among various methods, a more
convenient direct amidation is catalytic coupling of esters with
amines. This is a desirable approach for amide synthesis because
esters are usually economical and commercially available, as well
7
,8
as alcohols are the sole coproducts of this transformation.
Unlike more reactive phenolic esters, inert alkyl esters are not
2
2
and reuse.
HPAILs) have been prepared as hybrid materials by combining
Keggin heteropolyanions with ‘taskspecific’ ILs (TSILs) cations con-
Recently, a series of heteropolyanion-based ILs
(
⇑
Corresponding authors. Tel./fax: +86 512 52251842.
E-mail addresses: yangyangirisjs@126.com (Y. Yang), wangquanlzu@163.com
2
3
(
Q. Wang).
taining special functional groups. Because of the large volume
http://dx.doi.org/10.1016/j.tetlet.2015.05.118
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0

4
528
R. Fu et al. / Tetrahedron Letters 56 (2015) 4527–4531
and high valence of heteropolyanions and hydrogen bonding net-
works, HPAILs usually have high melting points, thermal stability
and chemical stability. These specialties are consistent with the
requirements of a solid acid catalyst in organic reactions resulting
in their advantages, such as operationally simplicity, no toxicity,
easily isolation, and reusability. So far, HPAILs have turned out to
be an eco-benign, high-efficient, and recyclable catalyst for acid-
X = PW O ,
12 40
1
-Methyl-3-(3-sulfopropyl)imidazolium
SO H
X3-
phosphotungstate ([MIMPS] PW 40);
O
12
3
3
N
N
3
X = PMo12
-Methyl-3-(3-sulfopropyl)imidazolium
hosphomolybdate ([MIMPS] PMo O40
O ,
40
1
)
3
12
X = PW12
1-(3-Sulfopropyl)pyridinium
phosphotungstate ([PyPS] PW12O40);
O ,
40
2
4
25
catalyzed or oxidative organic reactions.
X3-
3
On the other hand, a large number of publications have clearly
shown that many types of chemical transformations can be carried
out successfully under microwave (MW) conditions during the last
N
SO H 3
X = PMo O ,
12 40
3
1-(3-Sulfopropyl)pyridinium
hosphomolybdate ([PyPS]
PMo12O )
40
3
2
6
years. Most importantly, MW processing frequently leads to the
significant rate enhancements, yield and selectivity improvements,
very simplified ease of manipulation and work-up, less environ-
mental polluting processes as well as solvent-free organic transfor-
mations matching with the goal of green chemistry.26
X = PW12
O ,
40
Triethyl-(3-sulfopropyl)aminium
phosphotungstate ([TEAPS] PW12
X = PMo
C
2
H
5
X3-
3
O40);
C H
2 5
N
SO
H 3
3
O ,
12 40
C H
2
5
Triethyl-(3-sulfopropyl)aminium
hosphomolybdate ([TEAPS] PMo12O40
)
3
Recently, our group has introduced HPAILs as eco-benign and
highly efficient catalysts for amidations under MW-promoted
and solvent-free conditions.27 As a part of our continuing interest
in developing efficient and green protocols for catalytic methods
for amide bond formation, we wish to describe herein the prelim-
inary results on MW-promoted amidation of unactivated esters
catalyzed by HPAILs under solvent-free conditions (Scheme 1).
Based upon previous results of HPAIL catalyzed organic trans-
formations reported by our group,27,28 N-substituted imidazole,
pyridine, and triethylamine based HPAILs were chosen as potential
Figure 1. N-Substituted imidazole, pyridine, and triethylamine based HPAILs.
Table 1
Optimization of the reaction conditions for amidation of ethyl formate with aniline
a
catalyzed by HPAILs
Entry Catalyst
Temp (°C) Time (h)/min Yieldb (%)
1
2
3
4
5
6
7
8
9
1
1
1
No catalyst
[MIMPS] PW12O40, 2 mol %
rt
rt
(24)
(6)
33
63
3
c
c
catalysts for this amidation of unactivated esters (Fig. 1). Thus,
[MIMPS]
3
PW12
O
40, 2 mol %
[MIMPS] PW12O40, 2 mol %
50
70
100
70
70
70
(5) , 25
68 , 72
c
c
according to the procedure described in the literature2
4a,27,28
(3) , 10
90 , 95
3
six
c
c
[MIMPS]
[MIMPS]
[MIMPS]
[MIMPS]
[MIMPS]
[PyPS]
[PyPS]
[TEAPS]
3
3
3
3
3
PW12
PW12
PW12
PW12
O
O
O
O
40, 2 mol %
40, 2 mol %
40, 1 mol %
40, 3 mol %
(3) , 10
88 , 92
structurally related HPAILs were prepared.
d
10
15
10
15
10
15
20
25
15
90
90
92
85
96
90
85
73
71
Initially, some attempts to synthesize amides from esters and
amines were conducted using ethyl formate and aniline as model
reaction (Table 1). Firstly, a control experiment was performed
using 1.5 equiv of ethyl formate in the absence of any catalyst
and additional solvent at room temperature. After a prolonged
reaction time of 24 h N-phenylformamide was achieved in 33%
yield (Table 1, entry 1) whereas addition of 2 mol % amount of
PMo12
40, 2 mol %
40, 2 mol %
40, 2 mol %
[TEAPS] PMo12O40, 2 mol %
O40, 2 mol % 70
0
1
2
3
PW12
PMo12
PW12
O
O
O
70
70
70
70
70
3
3
13
14
3
3
H PW12O40, 2 mol %
[
MIMPS]
3
PW12
O
40 to the reaction mixture resulted in the desired
a
Unless otherwise noted, all reactions were carried out with ethyl formate
3.0 mmol), aniline (2.0 mmol), and related catalyst under MW (700 W) and sol-
amide product within 6 h in 63% yield (Table 1, entry 2). The
results revealed that the catalyzed amidation could be promoted
by HPAILs. Then it was shown that the rate and yield of the reac-
tion both increased when the reaction mixture was conventionally
heated at 50 °C for 5 h (Table 1, entry 3, 68% yield) or 70 °C for 3 h
(
vent-free conditions in a sealed tube.
b
Isolated yields.
Conventional heating.
Ethyl formate (4.0 mmol) and aniline (2.0 mmol) were used.
c
d
(Table 1, entry 4, 90% yield). But higher temperature (100 °C) was
not beneficial to the N-formyl product (Table 1, entry 5, 88% yield).
To our delight, when MW-assisted heating was introduced, more
efficient results were observed (Table 1, entries 3–5). Then, it
was observed that there is no need to use more excess of ethyl
formate, as a 1.5:1 molar ratio of ethyl formate to aniline was
sufficient to yield the desired product (Table 1, entry 6).
Moreover little lower yields were obtained in the presence of more
or less amount of catalyst (Table 1, entries 7 and 8). Afterward
catalytic activities of other related catalysts prepared before were
screened under the same reaction condition (Table 1, entry 4).
[PyPS]
alysts combining with different heteropolyanions, the results
demonstrated that PW12 40 was more active than PMo12
HPAILs (Table 1, entries 4, 9–13). When pure HPA catalyst
40 was used for this catalyzed amidation only 71% yield
was observed (Table 1, entry 14). Finally, optimum result was
obtained when the reaction was performed using 2 mol % of
3
[PyPS] PW12O40 under MW (700 W) and solvent-free condition at
3
PW12O40 (Table 1, entries 4, 10 and 12). In the cases of cat-
O
O
40
3
H PW12O
70 °C for 10 min affording N-phenylformamide in 96% yield
(Table 1, entry 10).
It was shown that the catalytic activities of [MIMPS]
3
PW12
O
40
With these promising results in hand, we examined the sub-
strate scope. The optimized reaction conditions were applied for
formylation of various aromatic and aliphatic primary or secondary
amines using formic esters as formylating agent (Table 2). Firstly,
with regard to the reactivities of formic esters, n-butyl formate,
i-butyl formate, benzyl formate, and more hindered i-propyl for-
mate were less reactive than ethyl formate in this procedure
(Table 2, 3a and 3b).
As shown in Table 2, various substituted anilines were con-
verted to corresponding N-formyl amides in good to excellent
yields. It was observed that aniline bearing substitution with an
electron donating group (methyl) provided an excellent yield of
97% with ethyl formate (Table 2, 3b) whereas, prolonged reaction
and [TEAPS]
3
PW12
O40 were slightly lower than that of
1
R2
O
R3
R
O
R3
O
N
R6
X
H
4
5
X = OH, NR R
HPAILs
MW irradiation
this work
HO R6
solvent-free
previous work
1
R2
R
O
X H
N
R3
Scheme 1. HPAIL catalyzed amidation reactions developed by our group.

R. Fu et al. / Tetrahedron Letters 56 (2015) 4527–4531
4529
Table 2
Table 3
a
a
HPAIL catalyzed amidation of formic ester with amines
HPAIL catalyzed amidation of esters with amines
O
O
O
2
[PyPS] PW12O (2 mol %)
O
3
R
H
3
3
40
R2
R
H [PyPS]
3
PW12
O
40 (2 mol %)
R3
N
1
N
R1
H
N
R
R OH
R1 OR2
N
R
2
H
OR1
4
R OH
R
2
MW, solvent-free
3
R
2
4
MW, solvent-free
1
3
4
5
6
4
b
b
Product: temp (°C)/time (min)/yield (%)
Product: temp (°C)/time (min)/yield (%)
NHCHO
NHCHO
NHCHO
H
N
H
N
O
N
Cl
c: 70/30/90
c
d
c
d
3
a: 70/10/96, 89 , 85 ,
3b: 70/10/97, 92 , 89 ,
d
3
O
O
6c: 100/30/93
e
f
e
f
8
3 , 78
86 , 82
c
6b: 100/30/91d
6
a: 120/60/51, 82 ,
NHCHO
NHCHO
d
92
O
2
N
3
N
NHCHO
H
O
H
N
N
n-C H
5 11
d: 100/50/67
3f: 100/30/81
N
n-C H
5 11
3
e: 100/20/89
O
O
NHNHCHO
N
NHCHO
3i: 70/10/91
7
b: 120/40/88
7
8
a: 120/60/82
8
a: 120/50/83
N
H
3
g: 70/15/92g
O
O
N
H
N
h
3
h: 70/30/90
N
H
O
b: 100/30/90
NHCHO
n-C
3
8
H17NHCHO
NHCHO
8c: 120/40/81
O
9
1
a: 140/60/—
k: 70/10/93
3
j: 70/10/93
3l: 70/15/81
H
N
H
N
H
N
CHO
N
NHCHO
N
O
O
O
3
m: 100/50/78
CHO
0a: 140/60/—
9b: 120/40/93
9
1
c: 120/60/90
3
o: 100/50/72
3
n: 100/45/85
H
N
O
O
CHO
N
CHO
N
p: 100/20/91
CHO
N
OH
OH
N
H
N
H
3
3q: 100/20/90
3r: 100/20/87
O
11b: 100/30/90e
e
1a: 100/50/92
1
0b: 120/50/85
a
Unless otherwise noted, all reactions were carried out with ethyl formate
3.0 mmol), amine (2.0 mmol), and related catalyst under MW (700 W) and solvent-
free conditions in a sealed tube.
O
O
O
O
(
CN
N
OC H
2 5
N
H
N
H
b
c
d
e
f
O
Isolated yields.
H
n-Butyl formate was used.
i-Butyl formate was used.
Benzyl formate was used.
Isopropyl formate was used.
o-Phenylenediamine was used.
Hydrazine was used.
12a: 100/30/85
13a: 100/30/87
14a: 90/40/88
O
O
O
O O
H
N
N
H
OC2H5
N
H
N
H
N
H
O
g
h
f
15a: 90/40/88
g
1
1
4b: 140/60/—
15b: 120/50/86
O
H
N
O
O
OC H
2
5
N
H
N
H
N
H
O
O
h
6a: 120/40/87
16b: 140/60/81
1
7a: 140/60/—
times and reduced yields were obtained when electron withdraw-
ing groups (chloro and nitro) were introduced in anilines
O
O
O
N
H
N
H
N
(Table 2, 3c and 3d). And the N-formylation procedure of hetero-
cyclic aromatic amines (naphthylamine and 2-aminopyridine)
was successfully completed within 30 min in 89% and 81% yields
at 100 °C (Table 2, 3e and 3f). When hydrazine was employed,
the reaction was rapidly and smoothly completed within 15 min
in 92% yield (Table 2, 3g) while N-formylation of aromatic diamine
1
1
7b: 140/40/90
17c: 140/50/86
17d: 140/50/85
O
O
O
N
H
N
H
N
H
Br
NO2
8a: 140/40/88
19a: 140/40/92
2
0a: 140/40/87
(
9
(
o-phenylene diamine) produced benzoimidazole within 30 min in
0% yield (Table 2, 3h). Moreover, with primary aliphatic amines
Table 2, 3i, 3j and 3k), good yields were achieved, while steric
O
N
O
N
H
N
O
hindrance could lead to less reactivities (Table 2, 3l and 3m). In
the cases of secondary amines, piperidine (Table 2, 3r) and more
hindered amines (Table 2, 3n, 3o, 3p and 3q) reacted well in this
procedure with higher reaction temperatures or longer reaction
times.
In order to further expand the substrate scope, other esters
were also selected to undergo the amidation. The summarized
results are shown in Table 3. In general, aromatic amines were less
reactive than aliphatic amines and afforded longer reaction times
and lower yields (Table 3, 6a vs 6b–6c, 7a vs 7b, 8a vs 8b–8c, 9a
vs 9b–9c, 10a vs 10b, 11a vs 11b, 17a vs 17b–17d). The good
conversions of linear chain aliphatic amines (Table 3, 8b, 9b,
22a: 140/50/90i
2
1a: 140/40/89
a
Unless otherwise noted, all reactions were carried out with ethyl ester
3.0 mmol), amine (2.0 mmol), and related catalyst under MW (700 W) and solvent-
(
free conditions in a sealed tube.
b
Isolated yields.
Allyl acetate was used.
Vinyl acetate was used.
,4-Butyrolactone was used.
c
d
e
1
f
g
h
i
Diethyl oxalate (2.0 mmol) and aniline (5.0 mmol) were used.
Diethyl malonate (2.0 mmol) and aniline (5.0 mmol) were used.
Diethyl succinate (2.0 mmol) and aniline (5.0 mmol) were used.
Diethyl phthalate was used.
1
0b, 11b, 17b, 18a–21a) to their corresponding amides were
poor nucleophiles, longer reaction times and lower yields were
achieved. Results show that steric hindrance and nucleophilicity
appeared to play an important role in the reactions.
observed, but in the case of hindered primary aliphatic amines
and secondary amines (Table 3, 7b, 8c, 9c, 17c, 17d) which are very

4
530
R. Fu et al. / Tetrahedron Letters 56 (2015) 4527–4531
Table 4
Reusability studies of the catalyst for the catalyzed amidation of estera
by the sulfonic group in HPAIL. The adsorbed ester–amine species
undergoes an addition of the amine to the carbonyl carbon atom to
obtain the dipolar adduct. After proton-exchange, subsequent
dealcoholization, and desorption, amide product was obtained
with regenerated catalyst. This bifunctional concept may be appli-
cable to the design of new HPAIL-catalyzed organic reactions.
In conclusion, we have successfully developed a microwave-
promoted HPAIL catalyzed approach for direct amidation of unac-
tivated esters under solvent-free conditions. A series of esters and
amines were tested and gave moderate to excellent yields.
Moreover, the HPAILs are recyclable and reused for more than five
cycles without showing significant loss in its catalytic activity. The
economic attractiveness, simple operation, solvent-free media,
reusable catalysts, and wide substrate scope will make the present
method a practical and important complement for the construction
of amides from readily available esters and amines.
Number of cycles
Yieldb (%)
1
96
2
94
3
90
4
89
5
89
a
Reaction conditions: ethyl formate (3.0 mmol), aniline (2.0 mmol), and related
catalyst under MW (700 W) and solvent-free conditions at 70 °C in a sealed tube.
b
Isolated yields.
O
O
O
S
X3-
2
R1 OR2
3
R
R1
N
N
OH 3
4
R
2
H
R OH
3
4
R N R
X3-
3
X3-
N
O S OH
2
N
O S O
2
H
3
-
+
R3
R4
δ
O
δ
δ
-
O
H
δ
R1
N
3
+
N R
R1 OR2
4
OHR2
R
Acknowledgments
X3-
N
O
2
S OH
Financial Support from National Natural Science Foundation of
China (Grant Nos. 21302013, 51203013), Natural Science
Foundation of Jiangsu Province (Grant No. BK2012207), Natural
Science Foundation of Jiangsu Educational Department (Grant No.
3
H
N R
O
R1
3
X = PW12O40
4
OR2
R
1
2KJB610001), Key University Science Research Project of Jiangsu
Figure 2. Plausible mechanism of HPAIL catalyzed amidation of ester.
Province (Grant No. 12KJA150001), Prospective Joint Research
Project of Jiangsu Province (Grant No. BY2013041) is
acknowledged.
With regard to the reactivities of the esters, linear chain
aliphatic acid esters (hexanoic acid ester, Table 3, 7a–7b, and
2
-phenylacetic acid ester, Table 3, 8a–8c) and hindered aliphatic
Supplementary data
acid esters (cyclohexanecarboxylic acid ester, Table 3, 9a–9c, and
pivalic acid ester, Table 3, 10a–10b) showed more reactivity than
aromatic acid esters (benzoic acid ester, Table 3, 17a–17d, 18a,
Supplementary data (general procedures and copies of the
H and C NMR spectra of all products) associated with this article
can be found, in the online version, at http://dx.doi.org/10.1016/j.
tetlet.2015.05.118.
1
13
1
9a, 20a) and heteroaromatic acid esters (nicotinic acid ester,
Table 3, 21a) in this procedure. It was worth mentioning that only
1% yield was obtained when using ethyl acetate (Table 3, 6a).
5
Maybe the low melting point of ethyl acetate is the reason while
more reactive acetic acid esters reacted well and gave the corre-
sponding product in good yields (Table 3, 6a–6c). When aromatic
amines were allowed to react with hindered aliphatic acid esters
and aromatic acid esters, the complete lack of reactivity was
observed even after prolonged reaction times and elevated
reaction temperatures (Table 3, 9a, 10a, 17a). And cyclic ester
References and notes
1
2
.
.
(a) Humphrey, J. M.; Chamberlin, A. R. Chem. Rev. 1997, 97, 2243–2266; (b)
Bode, J. W. Curr. Opin. Drug Disc. Dev. 2006, 9, 765–775; (c) Cupido, T.; Tulla-
Puche, J.; Spengler, J.; Albericio, F. Curr. Opin. Drug Disc. Dev. 2007, 10, 768–783;
(d) Wang, G.; Yuan, T.; Li, D. Angew. Chem., Int. Ed. 2011, 50, 1380–1383; (e)
Zhang, X.; Teo, W. T.; Chan, P. W. H. J. Organomet. Chem. 2011, 696, 331–337.
(a) Glomb, M. A.; Pfahler, C. J. Biol. Chem. 2001, 276, 41638–41647; (b) Armelin,
E.; Franco, L.; Rodríguez-Galan, A.; Puiggali, J. Macromol. Chem. Phys. 2002, 203,
48–58; (c) Fischbach, M. A.; Walsh, C. T. Chem. Rev. 2006, 106, 3468–3496; (d)
Valeur, E.; Bradley, M. Chem. Soc. Rev. 2009, 38, 606–631; (e) Kung, P.; Huang,
B.; Zhang, G.; Zhou, J. Z.; Wang, J.; Digits, J. A.; Skaptason, J.; Yamazaki, S.; Neul,
D.; Zientek, M.; Elleraas, J.; Mehta, P.; Yin, M.; Hickey, M. J.; Gajiwala, K. S.;
Rodgers, C.; Davies, J. F.; Gehring, M. R. J. Med. Chem. 2010, 53, 499–503.
(a) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol. Chem. 2006,
and a-electron-withdrawing group substituted esters reacted well
with aromatic and aliphatic amines (Table 3, 11a, 11b, 12a, 13a).
Moreover, in the cases of diesters the selective amidation was
achieved via the controllable conditions (Table 3, 14–16).
Unfortunately, amidation of diethyl oxalate produced mono-
amidated product as only main product even after a prolonged
reaction time of 60 min at 140 °C (Table 3, 14a–14b) while phthal-
imide was observed by using phthalic acid ester (Table 3, 22a).
The potential recycling of the catalyst was investigated in the
reaction of ethyl formate with aniline in the presence of 2 mol %
3
4
.
.
4, 2337–2447; (b) Butters, M.; Catterick, D.; Craig, A.; Curzons, A.; Dale, D.;
Gillmore, A.; Green, S. P.; Marziano, I.; Sherlock, J.-P.; White, W. Chem. Rev.
2006, 106, 3002–3027; (c) Roughley, S. D.; Jordan, A. M. J. Med. Chem. 2011, 54,
3451–3479; (d) Cooper, T. W. J.; Campbell, I. B.; Macdonald, S. J. F. Angew.
Chem., Int. Ed. 2010, 49, 8082–8091.
(a) Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.; Leazer, J. J. L.;
Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman, B. A.; Wells, A.; Zaks, A.;
Zhang, T. Y. Green Chem. 2007, 9, 411–420; (b) El-Faham, A.; Albericio, F. Chem.
Rev. 2011, 111, 6557–6602; (c) Stolze, S. C.; Kaiser, M. Synthesis 2012, 44, 1755–
[
(
PyPS]
monitored by TLC), EtOAc was added to the reaction mixture with
40 can be easily retrieved by
3
PW12O40 at 70 °C. After completion of the reaction
1777.
vigorous stirring and [PyPS]
3
PW12
O
5. (a) Han, S.; Kim, Y. Tetrahedron 2004, 60, 2447–2467; (b) Montalbetti, C. A. G.
N.; Falque, V. Tetrahedron 2005, 61, 10827–10852; (c) Zare, A.; Hasaninejad, A.;
Moosavi-Zare, A. R.; Parhami, A.; Khalafi-Nezhad, A. Asian J. Chem. 2009, 21,
simple centrifugation or filtration and drying at room temperature
under reduced pressure. The recycled catalyst was used in further
five runs with a little loss of catalytic efficiency (Table 4).
Although the reaction mechanism has not yet been elucidated,
the activation of carbonyl of carboxylic ester as well as the nucle-
ophilicity of amine appeared to play important roles in the amida-
tion procedure based on the above discussions. Thus, a plausible
mechanism for the reaction is depicted in Figure 2. The catalytic
cycle starts with the activation of carbonyl of carboxylic ester by
the coordination with aminium cation and N–H activation of amine
1090–1096.
6
.
For selected reviews, see: (a) Ekoue-Kovi, K.; Wolf, C. Chem. Eur. J. 2008, 14,
6302–6315; (b) Allen, C. L.; Williams, J. M. J. Chem. Soc. Rev. 2011, 40, 3405–
3415; (c) Pattabiraman, V. R.; Bode, J. W. Nature 2011, 480, 471–479; (d) Cheng,
C.; Hong, S. H. Org. Biomol. Chem. 2011, 9, 20–26; (e) Roy, S.; Roy, S.; Gribble, G.
W. Tetrahedron 2012, 68, 9867–9923; (f) Lanigan, R. M.; Sheppard, T. D. Eur. J.
Org. Chem. 2013, 33, 7453–7465; (g) Lundberg, H.; Tinnis, F.; Selander, N.;
Adolfsson, H. Chem. Soc. Rev. 2014, 42, 2714–2742.
For selected recent examples of catalytic direct amidation of esters, see: (a)
Han, C.; Lee, J. P.; Lobkovsky, E.; Porco, J. A., Jr. J. Am. Chem. Soc. 2005, 127,
10039–10044; (b) Sabot, C.; Kumar, K. A.; Meunier, S.; Mioskowski, C.
7
.

R. Fu et al. / Tetrahedron Letters 56 (2015) 4527–4531
4531
Tetrahedron Lett. 2007, 48, 3863–3866; (c) Yang, X.; Birman, V. B. Org. Lett.
009, 11, 1499–1502.
22. (a) Petkovic, M.; Seddon, K. R.; Rebelo, L. P. N.; Pereira, C. S. Chem. Soc. Rev.
2011, 40, 1383–1403; (b) Isambert, N.; Duque, M. M. S.; Plaquevent, J. C.;
Rodriguez, J.; Constantieux, T. Chem. Soc. Rev. 2011, 40, 1347–1357.
23. (a) Bourlinos, A. B.; Raman, K.; Herrera, R.; Zhang, Q.; Archer, L. A.; Giannelis, E.
P. J. Am. Chem. Soc. 2004, 126, 15358–15359; (b) Rickert, P. G.; Antonio, M. R.;
Firestone, M. A.; Kubatko, K. A.; Szreder, T.; Wishart, J. F.; Dietz, M. L. J. Phys.
Chem. B 2007, 111, 4685–4692; (c) Rickert, P. G.; Antonio, M. R.; Firestone, M.;
Kubatko, A. K. A.; Szreder, T.; Wishart, J. F.; Dietz, M. L. Dalton Trans. 2007, 529–
531.
24. (a) Leng, Y.; Wang, J.; Zhu, D.; Ren, X.; Ge, H.; Shen, L. Angew. Chem., Int. Ed.
2009, 48, 168–171; (b) Zhang, W.; Leng, Y.; Zhu, D.; Wu, Y.; Wang, J. Catal.
Commun. 2009, 11, 151–154; (c) Li, H.; Qiao, Y.; Hua, L.; Hou, Z.; Feng, B.; Pan,
Z.; Hu, Y.; Wang, X.; Zhao, X.; Yu, Y. ChemCatChem 2010, 2, 1165–1170; (d)
Zhang, W.; Leng, Y.; Zhao, P.; Wang, J.; Zhu, D.; Huang, J. Green Chem. 2011, 13,
832–834; (e) Fang, D.; Wang, F.; Wang, L.; Wu, Y.; Yang, J.; Qian, C. Curr. Catal.
2012, 1, 197–201; (f) Zhang, X.; Mao, D.; Leng, Y.; Zhou, Y.; Wang, J. Catal. Lett.
2013, 143, 193–199.
2
8
9
.
.
For selected other approaches toward environmentally benign amide
formation reactions, see: (a) Gunanathan, C.; Ben-David, Y.; Milstein, D.
Science 2007, 317, 790–792; (b) Gnanaprakasam, B.; Milstein, D. J. Am. Chem.
Soc. 2011, 133, 1682–1685; (c) Soulé, J.-F.; Miyamura, H.; Kobayashi, S. J. Am.
Chem. Soc. 2011, 133, 18550–18553; (d) Kang, B.; Fu, Z.; Hong, S. H. J. Am. Chem.
Soc. 2013, 135, 11704–11707.
Caldwell, N.; Jamieson, C.; Simpson, I.; Watson, A. J. B. ACS Sustainable Chem.
Eng. 2013, 1, 1339–1344.
0. Ohshima, T.; Hayashi, Y.; Agura, K.; Fujii, Y.; Yoshiyama, A.; Mashima, K. Chem.
Commun. 2012, 5434–5436.
1
1
1. Bundesmann, M. W.; Coffey, S. B.; Wright, S. W. Tetrahedron Lett. 2010, 51,
3
879–3882.
1
1
2. Veitch, G. E.; Bridgwood, K. L.; Ley, S. V. Org. Lett. 2008, 10, 3623–3625.
3. (a) Caldwell, N.; Jamieson, C.; Simpson, I.; Tuttle, T. Org. Lett. 2013, 15, 2506–
2
509; (b) Caldwell, N.; Campbell, P. S.; Jamieson, C.; Potjewyd, F.; Simpson, I.;
Watson, A. J. B. J. Org. Chem. 2014, 79, 9347–9354.
4. Weiberth, F. J.; Yu, Y.; Subotkowski, W.; Pemberton, C. Org. Process Res. Dev.
25. (a) Leng, Y.; Wang, J.; Zhu, D.; Zhang, M.; Zhao, P.; Long, Z.; Huang, J. Green
Chem. 2011, 13, 1636–1639; (b) Leng, Y.; Wang, J.; Zhu, D.; Shen, L.; Zhao, P.;
Zhang, M. Chem. Eng. J. 2011, 173, 620–626; (c) Leng, Y.; Zhang, W.; Wang, J.;
Jiang, P. Appl. Catal., A: Gen. 2012, 445–446, 306–311; (d) Qiao, Y.; Hou, Z.; Li, H.;
Hu, Y.; Feng, B.; Wang, X.; Hua, L.; Huang, Q. Green Chem. 2009, 11, 1955–1960.
26. (a) Tierney, J. P.; Lidström, P. Microwave Assisted Organic Synthesis; Blackwell
Publishing: Oxford, UK, 2005; (b) Dallinger, D.; Kappe, C. O. Chem. Rev. 2007,
107, 2563–2591; (c) Polshettiwar, V.; Varma, R. S. Acc. Chem. Res. 2008, 41,
629–639; (d) Kappe, C. O. Chem. Soc. Rev. 2008, 37, 1127–1139; (e) Kappe, C. O.;
Stadler, A.; Dallinger, D. In Microwaves in Organic and Medicinal Chemistry;
Mannhold, R., Kubinyi, H., Folkers, G., Eds.; Wiley-VCH Verlag GmbH & Co.
KGaA: Weinheim, Germany, 2012.
1
1
2
012, 16, 1967–1969.
5. Price, K. E.; Larriveée-Aboussafy, C.; Lillie, B. M.; McLaughlin, R. W.; Mustakis,
J.; Hettenbach, K. W.; Hawkins, J. M.; Vaidyanathan, R. Org. Lett. 2009, 11,
2
003–2006.
1
1
1
6. Movassaghi, M.; Schmidt, M. A. Org. Lett. 2005, 7, 2453–2456.
7. Han, Q.; Xiong, X.; Li, S. Catal. Commun. 2015, 58, 85–88.
8. Morimoto, H.; Fujiwara, R.; Shimizu, Y.; Morisaki, K.; Ohshima, T. Org. Lett.
2
014, 16, 2018–2021.
9. Bao, Y.; Zhaorigetu, B.; Agula, B.; Baiyin, M.; Jia, M. J. Org. Chem. 2014, 79, 803–
08.
1
2
2
8
0. Dubois, N.; Glynn, D.; McInally, T.; Rhodes, B.; Woodward, S.; Irvine, D. J.;
Dodds, C. Tetrahedron 2013, 69, 9890–9897.
1. (a) Whitten, K. M.; Makriyannis, A.; Vadivel, S. K. Tetrahedron Lett. 2012, 53,
27. (a) Chen, Z.; Fu, R.; Chai, W.; Zheng, H.; Sun, L.; Lu, Q.; Yuan, R. Tetrahedron
2014, 70, 2237–2245; (b) Fu, R.; Yang, Y.; Chen, Z.; Lai, W.; Ma, Y.; Wang, Q.;
Yuan, R. Tetrahedron 2014, 70, 9492–9499.
5
2
753–5755; (b) Luque, S.; Álvarez, J. R.; Cuperus, F. P. J. Mol. Catal. B: Enzym.
014, 107, 73–78.
28. Fu, R.; Yang, Y.; Lai, W.; Ma, Y.; Chen, Z.; Zhou, J.; Chai, W.; Wang, Q.; Yuan, R.
Synth. Commun. 2015, 45, 477–487.