An eco-benign and highly efficient procedure for N-acylation catalyzed by heteropolyanion-based ionic liquids using carboxylic acid under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2014.02.042

An eco-benign and highly efficient route for N-acylation of amines has been developed by treating amines with corresponding carboxylic acids in the presence of 2 mol % of heteropolyanion-based ionic liquids as catalysts under solvent-free conditions. This practical reaction could tolerate a wide range of substrates. Thus, various N-acylation products including N-acyl α-amino acid derivatives were obtained in moderate to excellent yields at 70 C to 120 C. Moreover, recycling studies revealed that heteropolyanion-based ionic liquids were easily reusable for this N-acylation. This method provides a green and much improved protocol over the existing methods.

Full text of DOI:10.1016/j.tet.2014.02.042

Tetrahedron 70 (2014) 2237e2245
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An eco-benign and highly efficient procedure for N-acylation
catalyzed by heteropolyanion-based ionic liquids using carboxylic
acid under solvent-free conditions
,
b
a
b
b
Zhikai Chen a, Renzhong Fu b , Wen Chai , Hao Zheng , Lin Sun , Qiang Lu ,
*
,
Rongxin Yuan b
*
a School of Petrochemical Engineering, Changzhou University, Changzhou 213164, PR China
b 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:
An eco-benign and highly efficient route for N-acylation of amines has been developed by treating
amines with corresponding carboxylic acids in the presence of 2 mol % of heteropolyanion-based ionic
liquids as catalysts under solvent-free conditions. This practical reaction could tolerate a wide range of
Received 2 September 2013
Received in revised form 7 January 2014
Accepted 18 February 2014
Available online 22 February 2014
substrates. Thus, various N-acylation products including N-acyl a-amino acid derivatives were obtained
in moderate to excellent yields at 70 ꢀC to 120 ꢀC. Moreover, recycling studies revealed that
heteropolyanion-based ionic liquids were easily reusable for this N-acylation. This method provides
a green and much improved protocol over the existing methods.
Keywords:
Amide
Green chemistry
Ionic liquid
Ó 2014 Elsevier Ltd. All rights reserved.
N-acylation
Solvent-free condition
1. Introduction
application of ILs in chemistry.8 Most recently,
a series of
heteropolyanion-based ILs (HPAILs) were prepared as hybrid ma-
terials by combining Keggin heteropolyanions with TSIL cations.9
These compounds are different from conventional ILs. In view of
the advantages of heteropolyanions and TSILs, HPAILs attract great
research interest due to their diverse chemical structures and im-
proved catalytic behaviours. The heteropolyanion existing in
HPAILs brings them high melting points and high thermal and
chemical stability, which is consistent with the requirements of
solid catalysts. Their solid nature is due to the extended hydrogen
bonding networks between the anion and cation. So far, HPAILs
have turned out to be an environmental-friendly, high-efficient and
reusable catalyst for acid-catalyzed10 or oxidative organic trans-
formations.11 Therefore, HPAILs have been proved to be a novel
candidate for catalytic green chemistry.
N-acylation, generally achieved by reaction between amines and
carboxylic derivatives, is one of the most important protocols in
organic and industrial chemicals synthesis.12 Amides are used as
key intermediates in the synthesis of a variety of medicinally active
compounds.13 Furthermore, amides act as useful reagents in the
Vilsmeier reaction,14 alkylation15 and hydrosilylation16 of carbonyl
compounds and synthesis of amidines and isocyanides.17 In addi-
tion, acyl group is a practical amino-protecting group in peptide
Nowadays, the development of non-toxic, eco-friendly, low cost,
recyclable catalysts, which give high productivity under mild re-
action conditions has received much attention in modern organic
synthesis.1 Over the past decades, ionic liquids (ILs) have emerged
as green reaction media and/or catalysts, which were different from
classical conventional ones owing to their unique properties, such
as low toxicity, negligible vapour pressure, low flammability, high
thermal and chemical stability, solvent power, reusability and
structural versatility.2 Some of ILs have been successfully used as
environmentally friendly alternative to traditional organic solvents
or catalysts in a number of organic reactions, such as esterification,3
DielseAlder reaction,4 FriedeleCrafts reaction5 and Biginelli con-
densation.6 Afterwards a variety of ‘task-specific’ ILs (TSILs) con-
taining special functional groups tethered to their cations or anions
were developed.7 TSILs have been exploited as efficient catalysts,
which could generally afford high yields and selectivities in a lot
of chemical transitions. Therefore, TSILs have expanded the
* Corresponding authors. Tel./fax: þ86 512 52251842; e-mail addresses: re-
nzhongfujs@126.com (R. Fu), yuanrx@cslg.edu.cn (R. Yuan).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.02.042

2238
Z. Chen et al. / Tetrahedron 70 (2014) 2237e2245
synthesis.18 Due to these important applications of amides, a large
number of methods were reported on N-acylation of amines in
recent years. Some of the practical reagents were KF-Al2O3,19 ZnO,20
polyethylene glycol,21 ZnCl2,22 sulfonic acid supported hydroxyap-
Table 1
Optimization of the reaction conditions for the N-formylation of aniline with formic
acid catalyzed by HPAILsa
Entry
Catalyst
Time (min)
Yield (%)b
atite encapsulated g
-Fe2O3,23 sodium formate,24 Amberlite IR120,25
1c
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 1 mol %
[MIMPS]3PW12O40, 3 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PW12O40, 2 mol %
[MIMPS]3PMo12O40, 2 mol %
[PyPS]3PW12O40, 2 mol %
[PyPS]3PMo12O40, 2 mol %
[TEAPS]3PW12O40, 2 mol %
[TEAPS]3PMo12O40, 2 mol %
H3PW12O40, 2 mol %
240
90
20
20
30
45
30
20
60
45
50
55
25
20
30
35
45
20
78
86
95
88
87
78
90
92
51
71
75
68
85
90
87
85
75
91
2d
3
indium metal,26 iodine,27 silica supported perchloric acid,28 sul-
fated tungstate29 and B(OCH2CF3)3.30 Microwave irradiation tech-
nique was used for N-acylation of amines to synthesize amide
compounds.31 Direct acylations using formic acid in sealed tube
without any additional solvent and catalyst was also reported.32
However, many of these methods suffered from various draw-
backs in the light of current working practice, such as using of
expensive and toxic acylating agents or catalysts and organic sol-
vents, high temperature, long reaction time, the acylation of by-
products and limited substrate scope. Just recently some re-
searchers reported ILs catalytic N-formylation.33 However, these ILs
inevitably showed some drawbacks, such as low yields, difficulty of
synthesis, relatively high catalyst amount and low recovery ratio.
Thus pursuit of more convenient, mild, high yielding and in-
expensive catalysts for N-acylation, which have no or minimal
harmful effect on our environment still remains an active area of
research. Herein, we wish to report an eco-benign and highly effi-
cient procedure for a wide substrate range of N-acylation catalyzed
by HPAILs using carboxylic acid under solvent-free conditions
(Scheme 1).
4e
5f
6g
7
8
9h
10i
11j
12k
13
14
15
16
17
18
a
Unless otherwise noted, reactions were conducted with aniline (2.0 mmol),
formic acid (3.0 mmol) and catalyst at 70 ꢀC.
b
Isolated yields.
c
Reaction was conducted under room temperature.
d
Reaction was conducted under 50 ꢀC.
e
Reaction was conducted under 100 ꢀC.
f
Aniline (2.0 mmol) and formic acid (6.0 mmol) were used.
Aniline (2.0 mmol) and formic acid (9.0 mmol) were used.
Toluene (1.0 mL) was used as solvent.
THF (1.0 mL) was used as solvent.
EtOH (1.0 mL) was used as solvent.
CH3CN (1.0 mL) was used as solvent.
g
h
i
j
k
rate and yield of the reaction both increased when the reaction
mixture was heated at 50 ꢀC for 90 min (Table 1, entry 2, 78% yield)
or 70 ꢀC for 20 min (Table 1, entry 3, 95% yield). But higher tem-
perature (100 ꢀC) was harmful to the N-formyl product (Table 1,
entry 4, 88% yield). The use of excess formic acid under the same
reaction condition afforded longer reaction time and lower yield
(Table 1, entries 5e6). Therefore, it was reasoned that the stoichi-
ometry of the formic acid is very important for this N-formylation.
Moreover a little lower yields were obtained in the present of more
or less amount of catalyst (Table 1, entries 7e8). In order to in-
vestigate the effect of the solvents, reactions were carried out in
toluene, THF, ethanol and acetonitrile (Table 1, entries 9e12). It was
observed that reaction time was increased (45e60 min) and a de-
crease was found in the yield (51%e75% yield) with any solvent.
Afterwards catalytic activities of other related catalysts prepared
before were investigated under the same reaction condition (Table
1, entry 3). It was shown that the catalytic activities of
[PyPS]3PW12O40 and [TEAPS]3PW12O40 were slightly lower than
that of [MIMPS]3PW12O40 (Table 1, entries 3, 14, 16). In the cases of
catalysts combining with different heteropolyanions, the results
demonstrated that PW12O40 was more active than PMo12O40
HPAILs (Table 1, entries 3, 13e17). Although pure HPA catalyst
H3PW12O40 gave a high yield of 91%, its good solubility throughout
organic solvents and water made its isolation from the reaction
mixture difficult (Table 1, entry 18). Finally, the use of 2 mol % of
related HPAILs gave some differences in the yields, amongst them
[MIMPS]3PW12O40 afforded the best result (Table 1, entry 3). En-
couraged by the remarkable results, various substituted amines
were used under this procedure for N-formylation to show gener-
ality and scope of this new protocol.
Scheme 1. N-acylation catalyzed by HPAILs.
2. Results and discussions
Amongst the various HPAILs, we were particularly interested in
N-substituted imidazole, pyridine and triethylamine based HPAILs
due to their easy accessibility, stability, low viscosity and easy re-
covery. Thus, six structurally related HPAILs (Fig. 1) were prepared
according to the procedure described in the literature10a for the
activation of carboxylic acid in the N-acylation.
Fig. 1. Structurally related HPAILs.
N-formylation of aniline using formic acid was chosen as model
reaction to determine the optimum condition (Table 1). Firstly,
aniline was allowed to react with formic acid (1.5 equiv) using
2 mol % amount of [MIMPS]3PW12O40 without any additional sol-
vent at room temperature and N-phenylformamide was achieved
within 4 h in 78% yield (Table 1, entry 1). Then it was shown that the
As shown in Table 2, aromatic and aliphatic primary or sec-
ondary amines reacted well with formic acid under this protocol. It
was observed that with primary aromatic amines, bearing sub-
stitution with an electron donating group (methoxyl or methyl,
Table 2, entries 2e3) on the aryl nucleus, the N-formylation was

Z. Chen et al. / Tetrahedron 70 (2014) 2237e2245
Table 2 (continued )
2239
Table 2
Synthesis of formamides catalyzed by HPAILa
Entry
Substrate
Time (min)
30
Product
Yield (%)b
92
17
Entry
1
Substrate
Time (min)
20
Product
Yield (%)b
95
18
19
60
30
91
87
2
3
20
20
96
94
20
21
22
20
25
40
90
88
88
4
5
6
20
20
50
93
92
93
23
60
90
24
25
26
90
45
90
91
88
d
7
8
45
50
91
90
No reaction
9
60
91
27
90
No reaction
d
10
11
12
50
70
90
82
87
90
28
29
60
60
81 (98% eec)
82 (99% eec)
30d
31
480
75 (87% eee)
13
14
20
30
82
92
20
90
85
32
No reaction
d
a
Reaction condition: amine (2.0 mmol), formic acid (3.0 mmol) and [MIM-
PS]3PW12O40 (2 mol %), 70 ꢀC.
15
16
50
60
82
88
b
Isolated yields.
c
Based on chiral HPLC by comparing with racemic counterpart.
d
Reaction condition: amine (2.0 mmol), formic acid (3.0 mmol) and [MIM-
PS]3PW12O40 (2 mol %), 100 ꢀC.
e
The ee values of the acids were determined for the corresponding methyl ester
by treatment with TMSCHN2.

2240
Z. Chen et al. / Tetrahedron 70 (2014) 2237e2245
rapidly and smoothly completed within 20 min in higher than 94%
yields. Whereas, the presence of electron withdrawing groups
(chloro, bromo, nitro, carbonyl and carboxylic, Table 2, entries
4e12) prolonged the reaction time to 90 min and reduced the yields
a little bit. In the case of 4-hydroxyaniline, N-formyl derivative was
obtained as the only main product (Table 2, entry 13). The result
indicated the excellent chemoselectivity of this N-formylation. And
the N-formylation procedure of naphthylamine was successfully
completed within 30 min in 92% yield (Table 2, entry 14). It was
worth mentioning that even heterocyclic aromatic amines (Table 2,
entries 15e16) and hydrazine derivatives (Table 2, entries 17e18)
reacted both well in this procedure. Interestingly, N-formylation of
aromatic diamine, o-phenylene diamine, produced benzoimidazole
in 87% yield instead of mono or di-formylated products (Table 2,
entry 19). Moreover, in the cases of primary aliphatic amines (Table
2, entry 20e21), good yields were achieved (88%e90% yield), which
normally showed poor yields.
coordination with HPAIL. Thus, carboxylic acid could be much more
active when it is attacked by the nucleophilic amine. The pro-
tonation and subsequent dehydration could produce amide and
regenerate the catalyst.
3. Conclusion
In conclusion, a series of HPAILs prepared by combining Keggin
heteropolyanions with TSIL cations acted as eco-benign and highly
efficient catalysts in N-acylation of amines using carboxylic acid.
Operational simplicity, solvent-free media, reusable catalysts and
the compatibility with various functional groups are the advan-
tages of this N-acylation procedure. Moreover, N-acyl a-amino acid
derivatives could be obtained via this catalytic method without any
racemization at 70 ꢀC, while obvious racemization was found due to
the acidic reaction condition and higher temperature. This strategy
complements the existing reports on the synthesis of amides. On
the basis of the findings of this report, the exploration of the cat-
alysts in other reactions and altering the composition of the cata-
lysts is in progress.
In the cases of secondary amines, piperidine (Table 2, entry 22)
and more hindered amines (Table 2, entries 23e24) reacted equally
well in this procedure with longer reaction time. In addition, N-
formyl imidazole was achieved in 88% yield, while benzoimidazole
or carbazole was completely inert to this N-formylation (Table 2,
entries 25e27).
4. Experimental section
4.1. General
In addition, this method was also applied to the synthesis of N-
formyl
for peptide synthesis. As shown in Table 2 entries 28e29, N-for-
mylation of -amino acid esters were readily achieved using the
a-amino acid derivatives, which serve as starting materials
Reagent grade solvents were used for extraction, re-
crystallization and flash chromatography. All other commercial
reagents were used as received without additional purification. The
progress of reactions was checked by analytical thin-layer chro-
matography (TLC, silica gel 60 F-254 plates). The plates were vi-
sualized first with UV illumination followed by iodine or
phosphomolybdic acid hydrate. Column chromatography was per-
formed using silica gel (200e300 mesh). NMR spectra were ob-
tained using BRUKER AVANCE III instrument. 1H NMR spectra were
recorded at 300 MHz and are reported in parts per million (ppm) on
a
present method without cleavage of the ester functional groups.
Furthermore, racemization was not observed via chiral HPLC
analysis by comparing with racemic counterparts. Higher temper-
ature (100 ꢀC) was required while
L-proline was used as N-for-
mylation substrate (Table 2, entry 30). Meanwhile, some
racemization occurred (87% ee) under the acidic reaction condition
and high temperature. In the cases of O-formylation, primary al-
cohols, such as benzyl alcohol, gave the benzyl alcohol ester in 85%
yield (Table 2, entry 31), while phenol failed to produce O-for-
mylated product (Table 2, entry 32). It is the reason that the nu-
cleophilicity of phenol is too weak to this catalytic reaction
conditions.
the
dard. 13C NMR spectra were recorded at 75 MHz and are reported in
parts per million (ppm) on the scale relative to CDCl3 ( 77.16) and
DMSO-d6 39.52). Multiplicities are indicated as the following: s,
d scale relative to tetramethylsilane (TMS) as an internal stan-
d
d
(d
Furthermore, other carboxylic acids were also selected to un-
dergo the amidation. The summarized results were shown in
Table 3. It was clearly indicated that the reaction of acetic acid,
propionic acid, and phenylacetic acid with aromatic and aliphatic
amines in the presence of 2 mol % [MIMPS]3PW12O40 gave good
yields at 100 ꢀC (Table 3, entries 1e5, 8, 9). Even cinnamide and
benzamide were obtained when using corresponding carboxylic
singlet; d, doublet; t, triplet; q, quartet; m, multiplet; dd, doubled
doublet; td, tripled doublet; br, broad. Coupling constants (J values)
where noted are quoted in hertz. Mass spectra were obtained using
Agilent 1260-6120 (ESI) instrument. Chiral HPLC analysis was ob-
tained using Agilent 1200 Series instrument with DAD detector. The
melting point was uncorrected.
acids as reagent (Table 3, entries 11, 12). Moreover, N-acyl
a
-amino
4.2. General procedure for the synthesis of catalysts10a
acid esters were achieved by treatment with related carboxylic acid
in the same reaction condition, while obvious racemization was
found due to the acidic reaction condition and high temperature
(Table 3, entries 6, 10, 13). In the cases of a-amino acid, N-acetyl-
phenylalanine was given in 73% yield (Table 3, entry 7).
Thus, the recycling of catalyst was also investigated. The re-
action of aniline with formic acid in the presence of 2 mol %
[MIMPS]3PW12O40 was studied. The outstanding feature of the
catalyst is its excellent solubility in water or strong polar solvents
but nonmiscibility with apolar esters. After completion of the re-
action (monitored by TLC), EtOAc was added to the reaction mix-
ture, and [MIMPS]3PW12O40 was removed by simple filtration after
vigorous stirring. After extraction and removal of the solvent, the
almost pure product was obtained. The catalyst could be reused
four times for the synthesis of N-phenylformamide with a little loss
of activity (Table 4). It was proved that HPAIL is easily reusable for
this N-acylation.
Methylimidazole (0.11 mol) and 1,3-propane sulfone (0.10 mol)
were dissolved in toluene (30 mL) and stirred for 24 h at 50 ꢀC under
a nitrogen atmosphere. A white precipitate (MIMPS) formed, which
was filtered, washed with diethyl ether three times, then dried in
a vacuum. MIMPS (0.09 mol) was added to an aqueous solution of
H3PW12O40 (0.03 mol), and then the mixture was stirred at room
temperature for 24 h. Water was removed in vacuum to give the
product [MIMPS]3PW12O40 as a solid. Thus [MIMPS]3PMo12O40
,
[PyPS]3PW12O40 [PyPS]3PMo12O40 [TEAPS]3PW12O40 and
,
,
[TEAPS]3PMo12O40 were prepared using according starting materials.
4.3. Generalprocedureforthe synthesisofformamides(Table 2)
To a mixture of amine (2 mmol) and formic acid (3 mmol) in
a 10 mL round bottomed flask was added [MIMPS]3PW12O40
(140 mg, 0.04 mmol). The reaction mixture was stirred at 70 ꢀC.
The progress of the reaction was monitored by TLC. On comple-
tion, the mixture was diluted with ethyl acetate (20 mL) with
A plausible mechanism for the reaction is depicted in Fig. 2. First
step is the activation of carbonyl of carboxylic acid by the

Z. Chen et al. / Tetrahedron 70 (2014) 2237e2245
2241
Table 3
Synthesis of amides catalyzed by HPAILa
Entry
1
Substrate
Time (min)
5
Product
Yield (%)b
92
2
5
94
3
4
5
12
5
91
93
88
6
6
7
87 (42% eec)
7d
20
73
8
6
91
9
8
7
87
10
90 (35% eec)
11
12
8
81
10
18
63
13
85 (5% eec)
a
Reaction condition: amine (2.0 mmol), carboxylic acid (6.0 mmol) and [MIMPS]3PW12O40 (2 mol %), 100 ꢀC.
Isolated yields.
Based on chiral HPLC by comparing with racemic counterpart.
Reaction condition: amine (2.0 mmol), carboxylic acid (6.0 mmol) and [MIMPS]3PW12O40 (2 mol %), 120 ꢀC.
b
c
d

2242
Z. Chen et al. / Tetrahedron 70 (2014) 2237e2245
Table 4
135.2, 134.5, 134.4, 134.2, 130.3, 129.6, 120.2, 119.1, 21.0, 20.9; MS
Reusability studies of catalyst for the synthesis of N-phenylformamidea
(ESI): m/z 136.1 [MþHþ].
Number of cycles
1
2
3
4
Yield (%)b
95
93
91
88
4.3.4. N-(4-Chlorophenyl)formamide (Table 2, entry 4). The pres-
ence of two rotamers (ratio 1:1) was observed in the NMR spectra.
Yellow solid. Mp: 104.3e106.4 ꢀC; IR (KBr): 3258, 1680, 1671, 1607,
a
Reaction condition: aniline (2.0 mmol), formic acid (3.0 mmol) and [MIM-
PS]3PW12O40 (2 mol %), 70 ꢀC.
1543 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
8.67 (d, J¼11.1 Hz, 1H), 8.61
b
Isolated yields.
(br s, 1H), 8.37 (d, J¼1.5 Hz, 1H), 7.59 (br s, 1H), 7.53e7.48 (m, 2H),
7.36e7.28 (m, 4H), 7.07e7.02 (m, 2H); 13C NMR (75 MHz, CDCl3)
d
162.7, 159.1, 135.5, 135.4, 130.8, 130.0, 129.3, 121.3, 120.2; MS (ESI):
m/z 156.0 [MþHþ].
4.3.5. N-(2-Bromophenyl)formamide (Table 2, entry 5). The pres-
ence of two rotamers (ratio 2:1) was observed in the NMR spectra.
Colourless solid. Mp: 88.1e90.5 ꢀC; IR (KBr): 3296, 1670, 1538, 1432,
; d 8.71
1400, 1295, 740 cmꢂ1 1H NMR (300 MHz, CDCl3)
(d, J¼11.1 Hz, 1H), 8.50 (d, J¼1.5 Hz, 1H), 8.40 (dd, J¼8.1, 1.2 Hz, 1H),
7.73 (br s, 2H), 7.61 (dd, J¼8.1, 0.9 Hz,1H), 7.56 (dd, J¼8.1,1.2 Hz,1H),
7.37e7.31 (m, 1H), 7.31e7.24 (m, 1H), 7.08 (td, J¼7.7, 1.5 Hz, 1H), 7.02
(td, J¼8.1, 1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3)
d 161.7, 159.0, 134.9,
133.7, 132.5, 128.8, 128.6, 126.5, 125.8, 122.3, 119.0, 114.5, 113.1; MS
(ESI): m/z 201.0 [MþHþ].
4.3.6. N-(4-Nitrophenyl)formamide (Table 2, entry 6). The presence
of two rotamers (ratio 3:1) was observed in the NMR spectra. Yel-
low solid. Mp: 193.5e195.8 ꢀC; IR (KBr): 3248, 3050, 2941, 2367,
1660, 1541, 1235 cmꢂ1; 1H NMR (300 MHz, DMSO-d6)
d 10.83 (br s,
1H), 10.72 (d, J¼9.0 Hz, 1H), 9.05 (d, J¼10.2 Hz, 1H), 8.40 (br s, 1H),
8.22 (d, J¼8.4 Hz, 2.5H), 7.93 (d, J¼8.4 Hz, 0.5H), 7.81 (d, J¼8.4 Hz,
2H), 7.41 (d, J¼7.8 Hz, 2H), 6.73 (br s, 0.5H), 6.58 (d, J¼8.7 Hz, 0.5H);
13C NMR (75 MHz, DMSO-d6)
d 162.9, 160.6, 144.3, 142.5, 125.5,
Fig. 2. Plausible mechanism of HPAIL promoted N-acylation of amines.
125.2, 119.0, 116.6; MS (ESI): m/z 167.0 [MþHþ].
4.3.7. N-(3-Nitrophenyl)formamide (Table 2, entry 7). The presence
of two rotamers (ratio 5:1) was observed in the NMR spectra. Yel-
low solid; mp: 137.5e138.9 ꢀC; 1H NMR (300 MHz, DMSO-d6)
stirring for 30 min. The insoluble catalyst was recovered by fil-
tration. The filtrate was washed with satd solution of NaHCO3
(5 mLꢁ3), brine, and dried over anhyd Na2SO4. The solvent
was evaporated and the residue in almost pure form. Re-
crystallization or column chromatography could be used for
further purification.
d
10.69 (br s, 1H), 10.50 (d, J¼10.5 Hz, 1H), 8.95 (d, J¼10.8 Hz, 1H),
8.61 (t, J¼1.8 Hz, 1H), 8.38 (d, J¼1.5 Hz, 1H), 8.02 (br s, 1H), 7.92 (dd,
J¼8.1, 1.4 Hz, 1H), 7.88 (dd, J¼7.8, 1.5 Hz, 1H), 7.68 (d, J¼8.1 Hz, 1H),
7.61 (t, J¼8.1 Hz, 1H); 13C NMR (75 MHz, DMSO-d6)
d 160.4, 148.0,
139.3, 130.4, 125.1, 118.2, 113.4; MS (ESI): m/z 167.0 [MþHþ].
4.3.1. N-Phenylformamide (Table 2, entry 1). The presence of two
rotamers (ratio 1:1) was observed in the NMR spectra. White solid.
Mp: 48.1e50.6 ꢀC; IR (KBr): 3300, 2877, 1650, 1540, 1438, 1403,
4.3.8. N-(2-Nitrophenyl)formamide (Table 2, entry 8). The presence
of two rotamers (ratio 5:1) was observed in the NMR spectra. Yel-
low solid. Mp: 122.1e125.0 ꢀC; IR (KBr): 3285, 1684, 1507,
1290 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 8.89 (br s, 1H), 8.71
(d, J¼11.4 Hz, 1H), 8.36 (d, J¼1.2 Hz, 1H), 7.92 (br s, 1H), 7.55
1337 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 10.34 (br s, 1H), 9.86 (br s,
(d, J¼7.5 Hz, 2H), 7.38e7.30 (m, 4H), 7.21e7.10 (m, 4H); 13C NMR
1H), 8.94 (br s, 1H), 8.82 (d, J¼8.4 Hz, 1H), 8.60 (br s, 1H), 8.26
(75 MHz, CDCl3)
d 163.1, 159.5, 137.0, 136.9, 129.8, 129.2, 125.3,
(dd, J¼8.4, 1.2 Hz, 1H), 7.69 (td, J¼8.0, 1.2 Hz, 1H), 7.51 (br, 1H),
124.9, 120.1, 118.8; MS (ESI): m/z 122.1 [MþHþ].
7.27e7.22 (m, 2H); 13C NMR (75 MHz, CDCl3)
d 159.6, 136.3, 133.8,
126.0, 124.1, 122.9; MS (ESI): m/z 167.0 [MþHþ].
4.3.2. N-(4-Methoxyphenyl)formamide (Table 2, entry 2). The pres-
ence of two rotamers (ratio 1:1) was observed in the NMR spectra.
Brown solid. Mp: 76.5e79.4 ꢀC; IR (KBr): 3246, 3052, 2890, 2939,
4.3.9. N-(2-Methoxy-5-nitrophenyl)formamide (Table 2, entry 9). The
presence of two rotamers (ratio >15:1) was observed in the NMR
spectra. Yellow solid. Mp: 208.1e209.8 ꢀC; 1H NMR (300 MHz,
2363, 1660, 1511, 1238 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 8.59 (br s,
1H), 8.51 (d, J¼11.4 Hz, 1H), 8.28 (d, J¼1.8 Hz, 1H), 7.86 (br s 1H),
DMSO-d6)
d
10.12 (br s,1H), 9.12 (d, J¼2.4 Hz,1H), 8.37 (br s,1H), 8.01
7.47e7.41 (m, 2H), 7.06e7.00 (m, 2H), 6.90e6.80 (m, 4H), 3.79
(dd, J¼9.0, 2.4 Hz, 1H), 7.25 (d, J¼9.3 Hz, 1H), 3.99 (s, 3H); 13C NMR
(s, 3H), 3.77 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
163.4, 159.3, 157.6,
(75 MHz, DMSO-d6) d 160.9, 153.5, 140.3, 127.2, 120.3, 114.4, 111.0,
156.7, 130.1, 129.7, 121.9, 121.6, 114.9, 114.2, 55.6, 55.5; MS (ESI): m/z
56.8; MS (ESI): m/z 197.0 [MþHþ].
152.1 [MþHþ].
4.3.10. N-(4-Acetylphenyl)formamide (Table 2, entry 10). The pres-
ence of two rotamers (ratio 4:3) was observed in the NMR spectra.
Yellow solid. Mp: 104.2e105.8 ꢀC; IR (KBr): 3246, 3052, 2939, 2366,
4.3.3. N-p-Tolylformamide (Table 2, entry 3). The presence of two
rotamers (ratio 1:1) was observed in the NMR spectra. White solid.
Mp: 51.5e53.3 ꢀC; IR (KBr): 3030, 1688, 1615, 1519, 1303 cmꢂ1
;
1H
1668, 1541, 1234 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 8.97 (br s, 1H),
NMR (300 MHz, CDCl3)
d
8.77 (br s, 1H), 8.63 (d, J¼11.4 Hz, 1H), 8.32
8.89 (d, J¼11.1 Hz, 1H), 8.46 (d, J¼1.5 Hz, 1H), 8.25 (br s, 1H), 7.97
(s, 1H), 7.85 (br s, 1H), 7.43 (d, J¼8.4 Hz, 2H), 7.13 (t, J¼8.4 Hz, 4H),
(t, J¼8.7 Hz, 4H), 7.70 (d, J¼8.7 Hz, 2H), 7.20 (d, J¼8.7 Hz, 2H), 2.61
6.99 (d, J¼8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3)
d
163.2, 159.4,
(s, 3H), 2.60 (s, 3H); 13C NMR (75 MHz, CDCl3)
d 197.4, 197.0, 162.2,

Z. Chen et al. / Tetrahedron 70 (2014) 2237e2245
2243
159.5, 141.5, 141.3, 133.7, 133.3, 130.6, 129.9, 119.3, 117.3, 26.7, 26.6;
(br s, 1H), 7.81 (br s, 1H), 7.23e7.12 (m, 4H), 6.81e6.71 (m, 6H); 13
C
MS (ESI): m/z 164.1 [MþHþ].
NMR (75 MHz, DMSO-d6)
d
167.8, 160.6, 149.5, 148.8, 129.0, 128.8,
119.5, 118.7, 112.4, 112.2; MS (ESI): m/z 137.1 [MþHþ].
4.3.11. 4-Formamidobenzoic acid (Table 2, entry 11). The presence of
two rotamers (ratio 3:1) was observed in the NMR spectra. Yellow
4.3.18. N0-(2,4-Dinitrophenyl)formohydrazide
(Table
2,
entry
solid. Mp: 258.1e261.3 ꢀC; 1H NMR (300 MHz, DMSO-d6)
d
12.76 (br
18). The presence of two rotamers (ratio 4:1) was observed in the
s, 2H), 10.51 (br s, 1H), 10.45 (d, J¼11.4 Hz, 1H), 8.95 (d, J¼10.8 Hz,
NMR spectra. Yellow solid. Mp: 196.8e198.0 ꢀC; 1H NMR (300 MHz,
1H), 8.34 (br s, 1H), 7.96e7.84 (m, 4H), 7.74e7.66 (m, 2H), 7.29
DMSO-d6)
d
10.46 (br s, 3H), 10.18 (br s, 2H), 8.85 (d, J¼2.4 Hz, 1H),
(d, J¼7.2 Hz, 2H); 13C NMR (75 MHz, DMSO-d6)
d
166.9, 162.7, 160.2,
8.40 (dd, J¼9.6, 2.4 Hz, 1H), 8.33 (dd, J¼9.3, 2.4 Hz, 1H), 8.25 (s, 1H),
142.7, 142.2, 131.0, 130.6, 125.6, 125.5, 118.6, 116.4; MS (ESI): m/z
8.13 (s, 1H), 7.36 (d, J¼9.6 Hz, 1H), 7.23 (d, J¼9.6 Hz, 1H); 13C NMR
166.0 [MþHþ].
(75 MHz, DMSO-d6)
d 160.5, 148.1, 136.8, 130.2, 129.8, 123.2, 115.5;
MS (ESI): m/z 227.0 [MþHþ].
4.3.12. Methyl 2-formamidobenzoate (Table 2, entry 12). The pres-
ence of two rotamers (ratio 5:1) was observed in the NMR spectra.
4.3.19. 1H-Benzo[d]imidazole (Table 2, entry 19). White solid. Mp:
182.0e183.3 ꢀC; IR (KBr): 3114, 3000, 1478, 1460, 1275, 1255, 752,
White solid. Mp: 49.1e50.5 ꢀC; 1H NMR (300 MHz, CDCl3)
d 10.98
777 cmꢂ1 1H NMR (300 MHz, DMSO-d6)
; d 12.44 (br s, 1H), 8.23
(br s, 1H), 10.45 (br s, 1H), 8.94 (d, J¼10.8 Hz, 1H), 8.70 (d, J¼8.1 Hz,
1H), 8.50 (br s, 1H), 8.03 (d, J¼7.8 Hz, 2H), 7.54 (t, J¼7.8 Hz, 2H), 7.36
(d, J¼7.8 Hz, 1H), 7.11 (t, J¼7.8 Hz, 2H), 3.92 (s, 6H); 13C NMR
(br s, 1H), 7.61e7.58 (m, 2H), 7.20e7.17 (m, 2H); 13C NMR (75 MHz,
CDCl3)
d
142.0, 138.2, 121.8, 115.4; MS (ESI): m/z 119.1 [MþHþ].
(75 MHz, CDCl3) d 168.6,161.4, 159.6,140.5,134.8,131.0, 123.2,121.2,
115.2, 52.5; MS (ESI): m/z 180.1 [MþHþ].
4.3.20. N-Benzylformamide (Table 2, entry 20). The presence of two
rotamers (ratio 5:1) was observed in the NMR spectra. White solid.
Mp: 60.4e62.8 ꢀC; IR (KBr): 1650 (C]O) cmꢂ1; 1H NMR (300 MHz,
4.3.13. N-(4-Hydroxyphenyl)formamide (Table 2, entry 13). The
presence of two rotamers (ratio 3:1) was observed in the NMR
spectra. Grey solid. Mp: 135.1e137.1 ꢀC; IR (KBr): 3580, 3396, 2952,
2848, 2207, 1664, 1517, 1020, 772 cmꢂ1; 1H NMR (300 MHz, DMSO-
CDCl3) d 8.22 (br s, 2H), 7.36e7.23 (m,10H), 6.20 (br s,1H), 5.13 (br s,
1H), 4.45 (d, J¼6.0 Hz, 2H), 4.38 (d, J¼6.3 Hz, 2H); 13C NMR (75 MHz,
CDCl3)
d 165.7, 161.2, 137.6, 129.0, 128.8, 128.0, 127.8, 127.7, 127.0,
45.7, 42.2; MS (ESI): m/z 136.1 [MþHþ].
d6)
d
9.91 (br s, 1H), 9.86 (d, J¼10.5 Hz, 1H), 9.03 (br s, 1H), 8.50
(d, J¼11.1 Hz, 1H), 8.16 (d, J¼1.5 Hz, 1H), 8.14 (br s, 1H), 7.38
4.3.21. N-Butylformamide (Table 2, entry 21). Colourless oil. 1H
(d, J¼9.0 Hz, 2H), 6.98 (d, J¼8.7 Hz, 2H), 6.73e6.69 (m, 2H),
6.51e6.43 (m, 2H); 13C NMR (75 MHz, DMSO-d6)
d 163.2, 162.7,
NMR (300 MHz, CDCl3)
d 8.44 (br s, 1H), 7.41 (br s, 1H), 2.85
158.9,154.3,153.6,148.7, 130.1, 129.7, 120.8, 120.2, 115.9, 115.7, 115.6,
(t, J¼7.5 Hz, 2H), 1.66e1.56 (m, 2H), 1.40e1.28 (m, 2H), 0.89
115.2; MS (ESI): m/z 138.0 [MþHþ].
(t, J¼7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3)
13.6; MS (ESI): m/z 102.1 [MþHþ].
d 169.2, 39.3, 29.7, 19.9,
4.3.14. N-(Naphthalen-1-yl)formamide (Table 2, entry 14). The
presenceoftworotamers(ratio5:2)wasobservedintheNMRspectra.
White solid. Mp: 125.8e127.3 ꢀC; IR (KBr): 3226, 1578, 1538, 1504,
4.3.22. N-Formylpiperidine (Table 2, entry 22). Colourless oil. IR
(KBr): 2940, 2860, 1588, 1441, 1400, 1369, 1348, 1328, 1280,
1396, 1270, 790 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
9.10 (d, J¼9.6 Hz,
1118 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 7.95 (br s, 1H), 3.42 (t,
1H), 8.64 (d, J¼11.1 Hz,1H), 8.60 (br s,1H), 8.05 (d, J¼7.8 Hz,1H), 7.99
(d, J¼7.5 Hz, 1H), 7.91e7.85 (m, 2H), 7.79 (d, J¼8.4 Hz, 1H), 7.71
(d, J¼8.1 Hz, 1H), 7.62e7.43 (m, 3H), 7.31 (d, J¼7.2 Hz, 1H); 13C NMR
J¼5.5 Hz, 2H), 3.36 (t, J¼5.5 Hz, 2H), 1.68e1.58 (m, 2H), 1.58e1.44
(m, 4H); 13C NMR (75 MHz, CDCl3)
d 160.9, 46.9, 40.7, 26.6, 25.1,
24.7; MS (ESI): m/z 114.1 [MþHþ].
(75 MHz, CDCl3) d 164.5, 160.0, 134.3, 134.1, 132.4, 131.1, 128.9, 128.6,
127.8, 127.1, 127.0, 126.9, 126.9, 126.3, 126.2, 125.8, 125.6, 121.5, 121.0,
4.3.23. N-Benzyl-N-(o-tolyl)formamide (Table 2, entry 23). The
120.6, 119.0; MS (ESI): m/z 172.1 [MþHþ].
presence of two rotamers (ratio 8:1) was observed in the NMR
spectra. Colourless oil; 1H NMR (300 MHz, CDCl3)
d
8.55 (br s, 1H),
8.16 (br s,1H), 7.31e7.10 (m,17H), 6.89e6.86 (m, 3H), 4.82 (br s, 2H),
2.09 (s, 3H), 2.01 (s, 3H); 13C NMR (75 MHz, CDCl3)
162.9, 161.8,
4.3.15. N-(Pyridin-2-yl)formamide (Table 2, entry 15). The presence
of two rotamers (ratio 1:1) was observed in the NMR spectra. Yel-
low solid. Mp: 34.1e36.5 ꢀC; IR (KBr): 3197, 2852, 1691, 1595, 1433,
d
139.0,136.4,136.1, 131.4, 131.1,129.2,129.1, 128.8,128.6,128.5,128.4,
128.3, 127.8, 127.7, 126.9, 126.8, 54.7, 49.5, 17.8, 17.7; MS (ESI): m/z
226.1 [MþHþ].
1303, 778, 517 cmꢂ1 1H NMR (300 MHz, DMSO-d6)
; d 10.60 (br s,
1H), 9.28 (d, J¼10.2 Hz, 1H), 8.32 (br s, 1H), 8.24 (d, J¼3.9 Hz, 1H),
8.06 (d, J¼8.1 Hz, 1H), 7.81e7.71 (m, 1H), 7.37e7.22 (m, 1H),
7.14e7.06 (m, 2H), 6.92 (d, J¼8.1 Hz, 1H); 13C NMR (75 MHz, DMSO-
4.3.24. N,N-Diphenylformamide (Table 2, entry 24). White solid.
Mp: 68.2e70.0 ꢀC; IR (KBr): 3062, 2918, 1659, 1595, 1496, 1446,
d6) d 169.2, 162.2, 160.4, 151.6, 148.1, 138.8, 138.4, 128.3, 127.3, 119.3,
113.8, 111.2; MS (ESI): m/z 123.0 [MþHþ].
1230 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
d
8.68 (s, 1H), 7.45e7.37
(m, 4H), 7.35e7.24 (m, 4H), 7.20e7.15 (m, 2H); 13C NMR (75 MHz,
4.3.16. Methyl 3-formamido-4-methylthiophene-2-carboxylate
(Table 2, entry 16). The presence of two rotamers (ratio 4:3) was
observed in the NMR spectra. Yellow solid. Mp: 127.0e129.7 ꢀC; 1H
CDCl3)
d 161.9, 141.9, 139.7, 129.8, 129.3, 127.2, 127.0, 126.3, 125.2;
MS (ESI): m/z 198.1 [MþHþ].
NMR (300 MHz, CDCl3)
d 9.22 (br s, 1H), 8.85 (br s, 1H), 8.77 (d,
4.3.25. N-Formyl imidazole (Table 2, entry 25). Colourless oil. 1H
J¼11.1 Hz, 1H), 8.82 (d, J¼8.4 Hz, 1H), 8.37 (br s, 1H), 7.18 (d,
J¼10.2 Hz, 1H), 3.88 (s, 6H), 2.34 (s, 3H), 2.24 (s, 3H); 13C NMR
NMR (300 MHz, CDCl3)
d
8.72 (s, 1H), 8.02 (m, 1H), 7.17 (d, J¼0.9 Hz,
2H); 13C NMR (75 MHz, CDCl3)
d 169.0, 157.7, 134.2, 120.6; MS (ESI):
(75 MHz, CDCl3) d 163.6,161.9, 158.8,141.4,135.9, 130.6,129.4,127.9,
m/z 97.0 [MþHþ].
52.3, 52.2, 16.7, 16.0; MS (ESI): m/z 200.0 [MþHþ].
4.3.17. N0-Phenylformohydrazide (Table 2, entry 17). The presence of
4.3.26. (S)-N-Formyl-ethyl-phenylalaninate (Table 2, entry 28).
Colourless oil. 98% ee. 1H NMR (300 MHz, CDCl3)
8.16 (br s, 1H),
7.32e7.22 (m, 3H), 7.17e7.11 (m, 2H), 6.24 (br s, 1H), 4.98e4.91
(m, 1H), 4.19 (q, J¼7.2 Hz, 2H), 3.15 (dd, J¼5.7, 2.7 Hz, 2H), 1.26
d
two rotamers (ratio 5:3) was observed in the NMR spectra. Yellow
solid. Mp: 121.0e123.6 ꢀC; 1H NMR (300 MHz, DMSO-d6)
d
9.73
(br s, 1H), 9.45 (d, J¼10.8 Hz, 1H), 8.12 (br s, 1H), 8.08 (br s, 1H), 8.02

2244
Z. Chen et al. / Tetrahedron 70 (2014) 2237e2245
(t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d171.2, 160.6, 135.6,
13C NMR (75 MHz, CDCl3)
d 170.4, 39.4, 31.6, 23.3, 20.1, 13.8; MS
129.4,128.7,127.3, 61.8, 51.9, 37.9,14.2; MS (ESI): m/z 222.1 [MþHþ].
(ESI): m/z 116.1 [MþHþ].
4.3.27. (S)-N-Formyl-ethyl-prolinate (Table 2, entry 29). The pres-
4.4.5. N-Acetylpiperidine (Table 3, entry 5). Colourless oil. IR (KBr):
ence of two rotamers (ratio 10:7) was observed in the NMR spectra.
3602, 3278, 3000, 2985, 1645, 1443, 1361, 1267, 1239, 980 cmꢂ1; 1H
Colourless oil. 99% ee. 1H NMR (300 MHz, CDCl3)
d
8.26 (s, 1H), 8.22
NMR (300 MHz, CDCl3) d 3.54 (br s, 2H), 3.39 (br s, 2H), 2.09 (s, 3H),
(s, 1H), 4.43e4.36 (m, 2H), 4.21e4.13 (m, 4H), 3.69e3.56 (m, 2H),
3.51 (t, J¼6.9 Hz, 2H), 2.28e2.15 (m, 3H), 2.02e1.86 (m, 5H),
1.68e1.50 (m, 6H); 13C NMR (75 MHz, CDCl3)
d 169.0, 47.6, 42.6,
26.6, 25.6, 24.6, 21.7; MS (ESI): m/z 128.1 [MþHþ].
1.28e1.22 (m, 6H); 13C NMR (75 MHz, CDCl3)
d 171.8, 171.7, 161.7,
160.8, 61.9, 61.4, 58.9, 56.6, 46.4, 44.0, 29.7, 29.5, 24.0, 22.9, 14.2,
4.4.6. (S)-N-Acetyl-ethyl-phenylalaninate (Table 3, entry 6). Yellow
solid. Mp: 107.0e109.2 ꢀC; 42% ee. 1H NMR (300 MHz, CDCl3)
14.1; MS (ESI): m/z 172.1 [MþHþ].
d
7.32e7.21 (m, 3H), 7.12e7.09 (m, 2H), 6.07 (br s, 1H), 4.90e4.83
4.3.28. (S)-N-Formyl-proline (Table 2, entry 30). The presence of
(m,1H), 4.17 (q, J¼7.2 Hz, 2H), 3.18e3.05 (m, 2H),1.98 (s, 3H),1.24 (t,
two rotamers (ratio 2:1) was observed in the NMR spectra. Col-
J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 171.8, 169.7, 136.0, 129.4,
ourless oil. 87% ee. 1H NMR (300 MHz, CDCl3)
d
8.32 (s, 1H), 8.30 (s,
128.6, 127.1, 61.6, 53.2, 38.0, 23.2, 14.2; MS (ESI): m/z 236.1 [MþHþ].
1H), 6.92 (br s, 2H), 4.52 (t, J¼6.9 Hz, 1H), 4.45 (t, J¼6.0 Hz, 1H), 3.66
(t, J¼6.9 Hz, 2H), 3.59e3.54 (m, 2H), 2.31e2.22 (m, 2H), 2.11e2.01
4.4.7. (S)-N-Acetyl-phenylalanine (Table 3, entry 7). Yellow solid.
(m, 2H), 2.00e1.90 (m, 4H); 13C NMR (75 MHz, CDCl3)
d
173.7, 173.3,
Mp: 145.0e147.2 ꢀC; 1H NMR (300 MHz, CDCl3)
d
7.32e7.25 (m, 3H),
7.17e7.15 (m, 2H), 6.08 (d, J¼7.2 Hz, 1H), 4.89e4.82 (m, 1H),
3.26e3.09 (m, 2H), 1.99 (s, 3H); 13C NMR (75 MHz, CDCl3)
173.7,
162.8,162.4, 59.0, 57.4, 47.1, 44.3, 29.8, 28.8, 24.1, 22.9; MS (ESI): m/z
144.1 [MþHþ].
d
170.5, 136.0, 129.5, 128.7, 127.2, 53.3, 37.4, 23.2; MS (ESI): m/z 208.1
[MþHþ].
4.3.29. Benzyl formate (Table 2, entry 31). Colourless oil. IR (KBr):
3068, 2937, 1725, 1596, 1499, 1260, 579 cmꢂ1 1H NMR (300 MHz,
;
CDCl3)
d
8.15 (br s, 1H), 7.39e7.36 (m, 5H), 5.21 (br s, 2H); 13C NMR
4.4.8. N-(p-Tolyl)propionamide (Table 3, entry 8). Yellow solid. Mp:
(75 MHz, CDCl3)
d
160.9, 135.3, 128.8, 128.6, 128.5, 65.8; MS (ESI):
122.0e124.2 ꢀC; 1H NMR (300 MHz, CDCl3)
d 7.66 (br s, 1H), 8.40
m/z 137.1 [MþHþ].
(d, J¼8.1 Hz, 2H), 7.09 (d, J¼7.8 Hz, 2H), 2.35 (q, J¼7.5 Hz, 2H), 2.29
(s, 3H), 1.21 (t, J¼7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 172.4,135.6,
4.4. General procedure for the synthesis of amides (Table 3)
133.8, 129.5, 120.1, 30.7, 20.9, 9.87; MS (ESI): m/z 164.1 [MþHþ].
To a mixture of amine (2 mmol) and carboxylic acid (6 mmol) in
a 10 mL round bottomed flask was added [MIMPS]3PW12O40
(140 mg, 0.04 mmol). The reaction mixture was stirred at 100 ꢀC.
The progress of the reaction was monitored by TLC. On completion,
the mixture was diluted with ethyl acetate (20 mL) with stirring for
30 min. The insoluble catalyst was recovered by filtration. The fil-
trate was washed with satd solution of NaHCO3 (5 mLꢁ3), brine,
and dried over anhyd Na2SO4. The solvent was evaporated and the
residue in almost pure form. Recrystallization or column chroma-
tography could be used for further purification.
4.4.9. N-Phenyl-2-phenylacetamide (Table 3, entry 9). Yellow solid.
Mp: 110.1e112.3 ꢀC; IR (KBr): 3446, 3030, 1648, 1605, 1540,
1498 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 7.43e7.05 (m, 10H), 7.07
(t, J¼7.4 Hz, 1H), 3.70 (s, 2H); 13C NMR (75 MHz, CDCl3)
d 169.4,
137.7, 134.6, 129.6, 129.3, 129.0, 127.7, 124.5, 120.0, 44.8; MS (ESI):
m/z 212.1 [MþHþ].
4.4.10. (S)-N-Phenylacetyl-ethyl-phenylalaninate (Table 3, entry
10). Yellow solid. Mp: 131.0e132.2 ꢀC; 35% ee. 1H NMR (300 MHz,
CDCl3)
d 7.36e7.28 (m, 3H), 7.21e7.17 (m, 5H), 6.92e6.89 (m, 2H),
5.87 (br s,1H), 4.86e4.80 (m,1H), 4.13 (q, J¼7.2 Hz, 2H), 3.55 (s, 2H),
4.4.1. N-Phenylacetamide (Table 3, entry 1). Yellow solid. Mp:
112.8e114.1 ꢀC; IR (KBr): 3294, 3261, 3196, 3137, 1665, 1600, 1558,
1500, 1491, 1435, 1369, 1324, 1266, 768, 760, 693, 534, 511 cmꢂ1; 1H
3.10e2.97 (m, 2H), 1.22 (t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d
171.4,170.5,135.7,134.5,129.5,129.3,129.1,128.6,127.5,127.1, 61.6,
53.1, 43.8, 37.7, 14.2; MS (ESI): m/z 312.2 [MþHþ].
NMR (300 MHz, CDCl3)
d 7.74 (br s, 1H), 7.53e7.49 (m, 2H),
7.34e7.26 (m, 2H), 7.13e7.07 (m, 1H), 2.16 (s, 3H); 13C NMR
4.4.11. N-Phenylcinnamamide (Table 3, entry 11). Yellow solid. Mp:
151.5e153.1 ꢀC; IR (KBr): 3274, 3061, 1659, 1623, 1598, 1540, 1495,
(75 MHz, CDCl3)
d 168.8, 138.0, 129.1, 124.4, 120.1, 24.6; MS (ESI):
m/z 136.1 [MþHþ].
1440, 1342, 1296, 1240, 1184, 988, 975, 900, 862 cmꢂ1 1H NMR
;
(300 MHz, DMSO-d6)
d
10.24 (br s, 1H), 7.72 (d, J¼7.8 Hz, 2H),
4.4.2. N-(p-Tolyl)acetamide (Table 3, entry 2). Yellow solid. Mp:
149.4e152.0 ꢀC; IR (KBr): 3421, 1664, 1606, 1550, 1540, 1380,
7.65e7.58 (m, 3H), 7.50e7.4 (m, 3H), 7.34 (t, J¼7.7 Hz, 2H), 7.07 (t,
J¼7.2 Hz, 1H), 6.86 (d, J¼15.6 Hz, 1H); 13C NMR (75 MHz, DMSO-d6)
768 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
d
7.56 (br s, 1H), 7.38
d 163.6, 140.2, 139.3, 134.7, 129.8, 129.1, 128.9, 127.8, 123.4, 122.3,
(d, J¼8.4 Hz, 2H), 7.10 (d, J¼8.1 Hz, 2H), 2.30 (s, 3H), 2.15 (s, 3H); 13
C
119.2; MS (ESI): m/z 224.1 [MþHþ].
NMR (75 MHz, CDCl3)
d 168.6, 135.4, 134.0, 129.5, 120.2, 24.6, 21.0;
MS (ESI): m/z 150.1 [MþHþ].
4.4.12. N-Phenylbenzamide (Table 3, entry 12). Yellow solid. Mp:
64.2e66.6 ꢀC; IR (KBr): 3346, 1657, 1601, 1579, 1536, 1493, 1449,
1440, 1329, 1301, 1262, 760, 716, 692, 683 cmꢂ1; 1H NMR (300 MHz,
4.4.3. N-(4-Nitrophenyl)acetamide (Table 3, entry 3). Yellow solid.
Mp: 207.8e208.9 ꢀC; IR (KBr): 3303, 1698, 1681, 1620, 1590, 1506,
DMSO-d6)
d
10.28 (br s, 1H), 7.96 (d, J¼6.6 Hz, 2H), 7.80 (d, J¼7.8 Hz,
1346, 1333, 1312, 1301 cmꢂ1; 1H NMR (300 MHz, DMSO-d6)
d 10.55
2H), 7.61e7.51 (m, 3H), 7.36 (t, J¼7.8 Hz, 2H), 7.10 (t, J¼7.2 Hz, 1H);
(br s, 1H), 8.19 (d, J¼8.1 Hz, 2H), 7.80 (d, J¼8.4 Hz, 2H), 2.11 (s, 3H);
13C NMR (75 MHz, DMSO-d6)
d 165.6, 139.2, 135.0, 131.6, 128.7,
13C NMR (75 MHz, DMSO-d6)
MS (ESI): m/z 181.1 [MþHþ].
d
169.4,145.5,142.0, 125.0, 118.5, 24.3;
128.4, 127.7, 123.7, 120.4; MS (ESI): m/z 198.1 [MþHþ].
4.4.13. (S)-N-Benzoyl-ethyl-phenylalaninate (Table 3, entry 13).
4.4.4. N-Butylacetamide (Table 3, entry 4). Colourless oil. IR (KBr):
Yellow solid. Mp: 113.0e115.2 ꢀC; 5% ee. 1H NMR (300 MHz, CDCl3)
3290, 3088, 2960, 2930, 2874, 1655, 1558, 1461, 1374, 1366 cmꢂ1; 1H
d 7.75e7.72 (m, 2H), 7.54e7.48 (m, 1H), 7.45e7.39 (m, 2H), 7.32e7.22
NMR (300 MHz, CDCl3)
(s, 3H), 1.48e1.39 (m, 2H), 1.33e1.21 (m, 2H), 0.87 (t, J¼7.2 Hz, 3H);
d
6.04 (br s, 1H), 3.18 (q, J¼6.6 Hz, 2H), 1.93
(m, 3H), 7.16e7.13 (m, 2H), 6.63 (d, J¼7.2 Hz, 1H), 5.10e5.04 (m, 1H),
4.21 (q, J¼7.2 Hz, 2H), 3.33e3.20 (m, 2H), 1.28 (t, J¼7.2 Hz, 3H); 13C

Z. Chen et al. / Tetrahedron 70 (2014) 2237e2245
2245
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Acknowledgements
Financial supported by National Nature Science Foundation of
China (Grant No. 21302013), Nature Science Foundation of Jiangsu
Province (Grant No. BK2012207), Nature Science Foundation of
Jiangsu Educational Department (Grant No. 12KJB150001), Foun-
dation of Jiangsu Laboratory of Advanced Functional Material
(Grant No. 12KFJJ008), China Postdoctoral Science Foundation
(Grant No. 20100480990) and Practice and Innovation Training
Project for Jiangsu College Students.
Supplementary data
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Copies of the 1H and 13C NMR spectra of all products and chiral
HPLC analysis for chiral
a-amino acid derivates. Supplementary
data related to this article can be found at http://dx.doi.org/10.1016/
j.tet.2014.02.042.
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