Synthesis of 2-(1-aryl-2-nitroethyl)-3-arylaminoacrylates via domino reaction of arylamines, methyl propiolate, and nitrostyrenes

Article abstract of DOI:10.1055/s-0031-1289718

An efficient synthetic protocol for 2-(1-aryl-2-nitroethyl)-3- arylaminoacrylates was successfully developed by the one-pot domino reaction of arylamines, methyl propiolate, and nitrostyrenes. The reaction involves the formation of -enamino ester and its

Full text of DOI:10.1055/s-0031-1289718

PAPER
1069
Synthesis of 2-(1-Aryl-2-nitroethyl)-3-arylaminoacrylates via
Domino Reaction of Arylamines, Methyl Propiolate, and Nitrostyrenes
2
-(1-Aryl-
i
2-nitr
o
n
ethyl)-3-aryl
g
aminoacrylate
s
Sun, Yan Sun, Hong Gao, Chao-Guo Yan*
College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, P. R. of China
Fax +86(514)87975531; E-mail: cgyan@yzu.edu.cn
Received 31 December 2011; revised 31 January 2012
cesses were observed by prolonging the reaction to sever-
al days at room temperature. Trying to carry out the
reaction at elevated temperature produces a very compli-
cated mixture due to the decomposition of the polysubsti-
tuted acrylate 1a. The preparation of 2-substituted 3-
aminoacrylate and 1-substituted 2-aminoalk-1-enyl ke-
tone derivatives by the reaction of 3-aminoacrylate and
alk-1-enyl-2-aminoketone derivatives with nitroethylenes
has been already reported.12 In order to explore the gener-
ality and scope of this domino reaction, other nitrosty-
renes were used in the reaction under the same conditions.
The results are summarized in Table 1. All of the reac-
tions proceeded smoothly to afford the corresponding 2-
(1-aryl-2-nitroethyl)-3-arylaminoacrylates 1a–q in satis-
factory yields (70–86%). The substituents with different
electronic effects on aromatic aldehydes showed marginal
effect to the reactivity. Arylamines with an electron-
donating alkyl or methoxy and with the weak electron-
withdrawing chloro group reacted efficiently to give the
expected products. Arylamines bearing strong electron-
withdrawing groups such as nitro group can not react with
methyl propiolate to give the desired intermediate b-
enamino ester, hence they could not be used in this domi-
no reaction.
Abstract: An efficient synthetic protocol for 2-(1-aryl-2-nitroeth-
yl)-3-arylaminoacrylates was successfully developed by the one-
pot domino reaction of arylamines, methyl propiolate, and nitrosty-
renes. The reaction involves the formation of b-enamino ester and
its sequential Michael addition to nitrostyrene.
Key words: domino reaction, b-enamino ester, electron-deficient
alkyne, nitrostyrene, acrylate
b-Enaminones and b-enamino esters represent important
building blocks for the synthesis of a wide variety of het-
erocycles and pharmaceutical compounds.1–4 They are
readily generated by the direct condensation of b-dicarbo-
nyl compounds with primary and secondary amines.5 On
the other hand, the addition of aliphatic and aromatic
amines to activated alkynes having carbonyl groups is
also a convenient method for preparation of b-enaminones
and b-enamino esters.6 The obtained b-enaminones and b-
enamino esters by this method could react further with se-
quential addition of nucleophilic or electrophilic reagents
to give versatile N,O-heterocycles.7–9 We have developed
several successful new domino reactions by using the in
situ formed b-enamino esters derived from the reactions
of arylamine with electron-deficient alkynes.10 Very re-
cently Balalaie and co-workers have reported the synthe-
sis of tetrasubstituted pyrroles by FeCl3-catalyzed three-
component reaction of primary amines, dialkyl acetylene-
dicarboxylates, and b-nitrostyrene derivatives.11The pub-
lication of this work prompted us to disclose our own
findings in this field. Herein, we report the one-pot domi-
no reaction of arylamines, methyl propiolate, and nitro-
styrenes for the efficient synthesis of the 2-(1-aryl-2-
nitroethyl)-3-arylaminoacrylates.
The structures of the 2-(1-aryl-2-nitroethyl)-3-arylamino-
acrylates 1a–q were characterized by elemental analyses,
1H and 13C NMR, MS, and IR spectra, and were further
confirmed by single-crystal X-ray diffraction performed
1
on the two compounds 1d and 1g (Figure 1).13 The H
NMR spectra of compounds 1a–q usually show one triplet
and two sets of dd peaks for the CHAr1CH2NO2 unit,
while the sign of the vinyl proton is usually overlapped
with the peaks of protons of the aromatic groups. For ex-
ample, in the 1H NMR spectrum of 1a, the one proton of
CHAr1 unit shows a triplet at 4.65 ppm with J = 7.8 Hz.
The two dd peaks at 4.98 and 4.88 ppm are typical signals
of two diasterotopic protons of methylene group
(CH2NO2). In the single crystal structures of compounds
1d and 1g, an intramolecular N–H···O hydrogen bond was
formed between the amino group and ester carbonyl
group; thus, the arylamino group and the ester group exist
The desired b-enamino ester was prepared in situ by the
reaction of 4-methoxyaniline with methyl propiolate in
ethanol at room temperature for overnight according to
the previously established reaction conditions.10 Then, ni-
trostyrene was added and the resulting mixture was stirred
at room temperature for additional 24 hours. After work-
up, the polysubstituted acrylate 1a was obtained in 72%
yield. The polysubstituted acrylate obviously comes from
the Michael addition of the in situ formed b-enamino ester
to nitrostyrene. No further reactions and cyclization pro-
1
in cis-position on the C=C double bond. The H NMR
spectra and the single crystal structures all indicated that
the prepared acrylate derivatives 1a–q exist in the thermo-
dynamically stable Z-configuration (arylamino group and
the ester group in cis-position on the C=C double bond),
in which intramolecular hydrogen bonding is possible. It
SYNTHESIS 2012, 44, 1069–1073
x
x.
x
x.
2
0
1
2
Advanced online publication: 17.02.2012
DOI: 10.1055/s-0031-1289718; Art ID: F118811SS
© Georg Thieme Verlag Stuttgart · New York

1070
J. Sun et al.
PAPER
Table 1 Synthesis of Polysubstituted Acrylates via Domino Reac-
tions
NO2
CO2Me
EtOH
r.t.
CO2Me
NHAr2
Ar1CH=CHNO2
Ar2NH2
Ar1
+
+
1
Entry Product Ar1
Ar2
Yield (%)
72
1
2
1a
1b
1c
1d
1e
1f
Ph
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
Ph
4-MeC6H4
4-t-BuC6H4
4-MeOC6H4
4-FC6H4
81
3
82
4
86
5
71
6
4-ClC6H4
4-BrC6H4
4-MeC6H4
Ph
80
7
1g
1h
1i
70
8
81
9
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
3-MeC6H4
4-ClC6H4
77
10
11
12
13
14
15
16
17
1j
4-MeC6H4
4-MeOC6H4
3-MeOC6H4
4-ClC6H4
4-BrC6H4
4-MeC6H4
4-MeC6H4
4-t-BuC6H4
80
Figure 1 Molecular structures of compounds 1d,g
1k
1l
83
agents are commercial reagents and used as received. Solvents were
purified by standard techniques.
80
1m
1n
1o
1p
1q
79
Domino Reaction of Arylamines, Methyl Propiolate, and
Nitrostyrenes; General Procedure
73
A mixture of arylamine (2.0 mmol) and methyl propiolate (0.168 g,
2.0 mmol) in EtOH (5 mL) was stirred at r.t. overnight. Then, ni-
trostyrene (2.0 mmol) was added and the solution was stirred at r.t.
for an additional 24 h. The resulting precipitate was collected by fil-
tration and washed with cold EtOH to give the pure product
(Table 1).
76
72
4-ClC6H4
78
also means that this domino reaction is a highly stereose-
lective reaction.
Methyl 2-(2-Nitroethyl-1-phenyl)-3-(4-methoxyphenylami-
no)acrylate (1a)
Yield: 0.510 g (72%); yellow solid; mp 97–98 °C.
In summary, we have developed a domino reaction of aryl-
amines, methyl propiolate, and nitrostyrenes, and found
an efficient and stereoselective protocol for the prepara-
tion of 2-(1-aryl-2-nitroethyl)-3-arylaminoacrylates in
good yields. This protocol has the advantages of mild re-
action conditions, easily accessible starting materials, and
easy purification of the products, which makes it a useful
and attractive method for the synthesis of the polysubsti-
tuted acrylates. The potential uses of the reaction in syn-
thetic and medicinal chemistry might be quite significant.
IR (KBr): 3212, 2940, 2837, 1676, 1629, 1545, 1513, 1447, 1378,
1315, 1217, 1129, 1031, 943, 824, 775 cm–1.
1H NMR (600 MHz, CDCl3): d = 9.98 (d, J = 12.6 Hz, 1 H, NH),
7.33 (t, J = 7.8 Hz, 2 H, ArH), 7.26 (d, J = 7.2 Hz, 3 H, ArH), 7.05
(d, J = 13.2 Hz, 1 H, CH), 6.83–6.79 (m, 4 H, ArH), 4.98 (dd,
3JHH = 12.5 Hz, 2JHH = 7.9 Hz, 1 H, CH), 4.88 (dd, 3JHH = 12.5 Hz,
2JHH = 8.2 Hz, 1 H, CH), 4.65 (t, J = 7.8 Hz, 1 H, CH), 3.75 (s, 3 H,
OCH3), 3.73 (s, 3 H, OCH3).
13C NMR (150 MHz, CDCl3): d = 169.2, 155.9, 145.0, 139.1, 134.1,
128.8, 127.6, 127.3, 117.5, 115.0, 96.2, 78.1, 55.6, 51.0, 44.3.
MS: m/z (%) = 379.38 ([M + Na], 100).
All reactions were monitored by TLC. Melting points were taken on
a hot-plate microscope apparatus. IR spectra were obtained on a
Bruker Tensor 27 spectrometer (KBr disc). NMR spectra were re-
corded with a Bruker AV-600 spectrometer with DMSO-d6 as sol-
vent and TMS as internal standard (600 and 150 MHz for 1H and 13C
NMR spectra, respectively). Elemental analyses were obtained on
Thermo Flash 2000 instrument. HPLC/MS analyses were carried
out using a Fennigan LCQ Deca XP MAX instrument. Aromatic al-
dehydes, arylamines, nitromethane, methyl propiolate, and other re-
Anal. Calcd for C19H20N2O5: C, 64.04; H, 5.66; N, 7.86. Found: C,
63.85; H, 5.80; N, 7.51.
Methyl 2-[1-(4-Methylphenyl)-2-nitroethyl]-3-(4-methoxyphe-
nylamino)acrylate (1b)
Yield: 0.598 g (81%); yellow solid; mp 129–130 °C.
IR (KBr): 3302, 3010, 2953, 2838, 1672, 1619, 1546, 1515, 1454,
1374, 1298, 1218, 1038, 952, 821 cm–1.
Synthesis 2012, 44, 1069–1073
© Thieme Stuttgart · New York

PAPER
2-(1-Aryl-2-nitroethyl)-3-arylaminoacrylates
1071
1H NMR (600 MHz, CDCl3): d = 9.97 (d, J = 12.0 Hz, 1 H, NH),
7.14 (br s, 4 H, ArH), 7.05 (d, J = 12.6 Hz, 1 H, CH), 6.84–6.80 (m,
4 H, ArH), 4.96 (dd, 3JHH = 12.3 Hz, 2JHH = 7.9 Hz, 1 H, CH), 4.85
(dd, 3JHH = 12.3 Hz, 2JHH = 8.4 Hz, 1 H, CH), 4.62 (t, J = 7.8 Hz, 1
H, CH), 3.76 (s, 3 H, OCH3), 3.74 (s, 3 H, OCH3), 2.32 (s, 3 H,
CH3).
MS: m/z (%) = 397.54 ([M + Na], 100).
Anal. Calcd for C19H19FN2O5: C, 60.96; H, 5.12; N, 7.48. Found: C,
60.73; H, 5.40; N, 7.39.
Methyl 2-[1-(4-Chlorophenyl)-2-nitroethyl]-3-(4-methoxyphen-
ylamino)acrylate (1f)
Yield: 0.620 g (80%); light yellow solid; mp 100–102 °C.
13C NMR (150 MHz, CDCl3): d = 169.3, 155.9, 144.9, 137.0, 135.9,
134.2, 129.5, 127.4, 117.4, 115.0, 96.3, 78.3, 55.6, 51.0, 43.9, 21.0.
IR (KBr): 3297, 2952, 1671, 1619, 1549, 1514, 1452, 1371, 1298,
1219, 1104, 1035, 951, 825 cm–1.
MS: m/z (%) = 393.28 ([M + Na], 100).
Anal. Calcd for C20H22N2O5: C, 64.85; H, 5.99; N, 7.56. Found: C,
64.70; H, 6.36; N, 7.29.
1H NMR (600 MHz, CDCl3): d = 9.97 (d, J = 12.6 Hz, 1 H, NH),
7.29 (d, J = 8.4 Hz, 2 H, ArH), 7.19 (d, J = 8.4 Hz, 2 H, ArH), 7.06
(d, J = 12.6 Hz, 1 H, CH), 6.84 (br s, 4 H, ArH), 4.95 (dd, 3JHH
12.7 Hz, 2JHH = 7.8 Hz, 1 H, CH), 4.85 (dd, 3JHH = 12.7 Hz, 2JHH
=
=
Methyl 2-[1-(4-tert-Butylphenyl)-2-nitroethyl]-3-(4-methoxy-
phenylamino)acrylate (1c)
8.2 Hz, 1 H, CH), 4.59 (t, J = 7.8 Hz, 1 H, CH), 3.76 (s, 3 H, OCH3),
Yield: 0.678 g (82%); white solid; mp 122–124 °C.
3.71 (s, 3 H, OCH3).
IR (KBr): 3297, 2959, 1670, 1620, 1551, 1513, 1445, 1372, 1293,
1216, 1031, 948, 828, 787 cm–1.
13C NMR (150 MHz, CDCl3): d = 169.0, 156.0, 144.9, 137.8, 133.9,
133.1, 128.9, 117.6, 115.0, 95.8, 77.9, 55.6, 51.1, 43.9.
1H NMR (600 MHz, CDCl3): d = 9.96 (d, J = 12.0 Hz, 1 H, NH),
7.34 (d, J = 7.8 Hz, 2 H, ArH), 7.18 (d, J = 8.4 Hz, 2 H, ArH), 7.05
MS: m/z (%) = 413.20 ([M + Na], 100).
Anal. Calcd for C19H19ClN2O5: C, 58.39; H, 4.90; N, 7.17. Found:
C, 58.53; H, 5.27; N, 6.87.
(d, J = 13.2 Hz, 1 H, CH), 6.83–6.79 (m, 4 H, ArH), 4.99 (dd, 3JHH
12.4 Hz, 2JHH = 8.1 Hz, 1 H, CH), 4.86 (dd, 3JHH = 12.4 Hz, 2JHH
=
=
8.1 Hz, 1 H, CH), 4.62 (t, J = 7.8 Hz, 1 H, CH), 3.76 (s, 3 H, OCH3),
3.74 (s, 3 H, OCH3), 1.30 (s, 9 H, CH3).
13C NMR (150 MHz, CDCl3): d = 169.3, 155.9, 150.2, 145.0, 136.0,
134.2, 127.2, 125.7, 117.4, 115.0, 96.3, 78.3, 55.6, 51.0, 44.0, 34.5,
31.3.
Methyl 2-[1-(4-Bromophenyl)-2-nitroethyl]-3-(4-methoxyphen-
ylamino)acrylate (1g)
Yield: 0.606 g (70%); light yellow solid; mp 138–140 °C.
IR (KBr): 3296, 2952, 1671, 1619, 1550, 1514, 1452, 1371, 1298,
1223, 1035, 950, 825 cm–1.
MS: m/z (%) = 435.44 ([M + Na], 100).
1H NMR (600 MHz, CDCl3): d = 9.98 (d, J = 12.6 Hz, 1 H, NH),
7.46 (d, J = 8.4 Hz, 2 H, ArH), 7.14 (d, J = 8.4 Hz, 2 H, ArH), 7.06
Anal. Calcd for C23H28N2O5: C, 66.97; H, 6.84; N, 6.79. Found: C,
66.63; H, 6.57; N, 6.63.
(d, J = 12.6 Hz, 1 H, CH), 6.86–6.83 (m, 4 H, ArH), 4.96 (dd, 3JHH
12.7 Hz, 2JHH = 7.9 Hz, 1 H, CH), 4.88 (dd, 3JHH = 12.7 Hz, 2JHH
=
=
Methyl 2-[1-(4-Methoxyphenyl)-2-nitroethyl]-3-(4-methoxy-
phenylamino)acrylate (1d)
8.2 Hz, 1 H, CH), 4.57 (t, J = 7.8 Hz, 1 H, CH), 3.78 (s, 3 H, OCH3),
3.72 (s, 3 H, OCH3).
Yield: 0.662 g (86%); light yellow solid; mp 116–118 °C.
13C NMR (150 MHz, CDCl3): d = 169.0, 156.0, 145.0, 138.3, 133.9,
IR (KBr): 3299, 2951, 2837, 1670, 1618, 1549, 1512, 1453, 1371,
1302, 1217, 1032, 951, 830, 778 cm–1.
131.9, 129.2, 121.2, 117.6, 115.0, 95.7, 77.9, 55.6, 51.1, 44.0.
MS: m/z (%) = 458.57 ([M + Na], 100).
1H NMR (600 MHz, CDCl3): d = 9.96 (d, J = 12.6 Hz, 1 H, NH),
Anal. Calcd for C19H19BrN2O5: C, 52.43; H, 4.40; N, 6.44. Found:
C, 52.28; H, 4.76; N, 6.21.
7.18 (d, J = 8.4 Hz, 2 H, ArH), 7.03 (d, J = 12.6 Hz, 1 H, CH), 6.87
(d, J = 9.0 Hz, 2 H, ArH), 6.83–6.79 (m, 4 H, ArH), 4.95 (dd, 3JHH
12.5 Hz, 2JHH = 7.6 Hz, 1 H, CH), 4.82 (dd, 3JHH = 12.5 Hz, 2JHH
=
=
Methyl 2-[1-(4-Methylphenyl)-2-nitroethyl]-3-phenylamino-
acrylate (1h)
Yield: 0.554 g (81%); white solid; mp 124–126 °C.
8.5 Hz, 1 H, CH), 4.62 (t, J = 7.8 Hz, 1 H, CH), 3.78 (s, 3 H, OCH3),
3.75 (s, 3 H, OCH3), 3.74 (s, 3 H, OCH3).
13C NMR (150 MHz, CDCl3): d = 169.2, 158.7, 155.9, 144.8, 134.1,
130.9, 128.7, 117.4, 115.0, 114.9, 114.2, 96.5, 78.4, 55.6, 55.3,
51.0, 43.6.
IR (KBr): 3292, 2952, 1673, 1594, 1545, 1506, 1439, 1373, 1307,
1231, 1197, 1148, 996, 944, 829, 751 cm–1.
1H NMR (600 MHz, CDCl3): d = 10.06 (d, J = 12.0 Hz, 1 H, NH),
7.27 (t, J = 7.8 Hz, 2 H, ArH), 7.16–7.14 (m, 5 H, ArH, CH), 6.99
(t, J = 7.2 Hz, 1 H, ArH), 6.86 (d, J = 7.8 Hz, 1 H, ArH), 4.96 (dd,
3JHH = 12.4 Hz, 2JHH = 7.9 Hz, 1 H, CH), 4.85 (dd, 3JHH = 12.4 Hz,
2JHH = 8.4 Hz, 1 H, CH), 4.64 (t, J = 7.8 Hz, 1 H, CH), 3.74 (s, 3 H,
OCH3), 2.32 (s, 3 H, CH3).
13C NMR (150 MHz, CDCl3): d = 169.2, 143.8, 140.5, 137.1, 135.8,
129.8, 129.7, 129.5, 127.5, 127.1, 123.0, 115.8, 115.6, 97.6, 78.2,
51.2, 43.9, 21.0.
MS: m/z (%) = 409.41 ([M + Na], 100).
Anal. Calcd for C20H22N2O6: C, 62.17; H, 5.74; N, 7.25. Found: C,
62.15; H, 6.06; N, 7.11.
Methyl 2-[1-(4-Fluorophenyl)-2-nitroethyl]-3-(4-methoxyphen-
ylamino)acrylate (1e)
Yield: 0.534 g (71%); white solid; mp 78–80 °C.
IR (KBr): 3210, 2944, 2836, 1674, 1629, 1550, 1512, 1447, 1376,
1317, 1225, 1129, 1033, 997, 947, 828, 780 cm–1.
MS: m/z (%) = 363.59 ([M + Na], 100).
1H NMR (600 MHz, CDCl3): d = 9.97 (d, J = 12.6 Hz, 1 H, NH),
7.24–7.22 (m, 2 H, ArH), 7.05–7.01 (m, 3 H, ArH, CH), 6.83–6.81
(m, 4 H, ArH), 4.96 (dd, 3JHH = 12.5 Hz, 2JHH = 7.8 Hz, 1 H, CH),
4.85 (dd, 3JHH = 12.5 Hz, 2JHH = 8.4 Hz, 1 H, CH), 4.62 (t, J = 7.8
Hz, 1 H, CH), 3.76 (s, 3 H, OCH3), 3.73 (s, 3 H, OCH3).
13C NMR (150 MHz, CDCl3): d = 169.0, 161.1, 156.0, 144.9, 134.8,
134.0, 129.1, 129.0, 117.5, 115.7, 115.6, 115.0, 96.1, 78.2, 55.6,
51.1, 43.7.
Anal. Calcd for C19H20N2O4: C, 67.05; H, 5.92; N, 8.23. Found: C,
66.84; H, 6.22; N, 8.20.
Methyl 2-(2-Nitroethyl-1-phenyl)-3-(4-methylphenylami-
no)acrylate (1i)
Yield: 0.522 g (77%); white solid; mp 104–106 °C.
IR (KBr): 3295, 3022, 2956, 1674, 1617, 1549, 1445, 1371, 1303,
1200, 1150, 997, 950, 820, 780 cm–1.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1069–1073

1072
J. Sun et al.
PAPER
1H NMR (600 MHz, CDCl3): d = 10.01 (d, J = 12.6 Hz, 1 H, NH),
7.34–7.32 (m, 2 H, ArH), 7.26–7.23 (m, 3 H, ArH), 7.11 (d, J = 12.6
Hz, 1 H, CH), 7.06 (d, J = 7.8 Hz, 2 H, ArH), 6.76 (d, J = 7.8 Hz, 2
H, ArH), 4.98 (dd, JHH = 12.6 Hz, JHH = 7.8 Hz, 1 H, CH), 4.88
(dd, 3JHH = 12.5 Hz, 2JHH = 7.2 Hz, 1 H, CH), 4.66 (t, J = 7.8 Hz, 1
H, CH), 3.73 (s, 3 H, OCH3), 2.27 (s, 3 H, CH3).
MS: m/z (%) = 393.24 ([M + Na], 100).
Anal. Calcd for C20H22N2O5: C, 64.85; H, 5.99; N, 7.56. Found: C,
64.65; H, 6.10; N, 7.67.
3
2
Methyl 2-[1-(4-Chlorophenyl)-2-nitroethyl]-3-(4-methylphen-
ylamino)acrylate (1m)
Yield: 0.590 g (79%); light yellow solid; mp 116–118 °C.
13C NMR (150 MHz, CDCl3): d = 169.1, 144.4, 139.0, 138.1, 132.7,
130.2, 128.8, 127.6, 127.4, 115.9, 96.8, 78.1, 51.1, 44.3, 20.7.
IR (KBr): 3298, 2951, 1674, 1613, 1548, 1447, 1370, 1305, 1277,
1197, 1149, 1003, 945, 823, 784 cm–1.
MS: m/z (%) = 363.46 ([M + Na], 100).
Anal. Calcd for C19H20N2O4: C, 67.05; H, 5.92; N, 8.23. Found: C,
66.91; H, 6.03; N, 7.84.
1H NMR (600 MHz, CDCl3): d = 10.01 (d, J = 12.6 Hz, 1 H, NH),
7.31 (d, J = 9.6 Hz, 2 H, ArH), 7.20 (d, J = 8.4 Hz, 2 H, ArH), 7.11
(d, J = 13.2 Hz, 1 H, CH), 7.09 (d, J = 8.4 Hz, 2 H, ArH), 4.96 (dd,
3JHH = 12.7 Hz, 2JHH = 7.8 Hz, 1 H, CH), 4.86 (dd, 3JHH = 12.7 Hz,
2JHH = 8.3 Hz, 1 H, CH), 4.60 (t, J = 7.8 Hz, 1 H, CH), 3.73 (s, 3 H,
OCH3), 2.29 (s, 3 H, CH3).
Methyl 2-[1-(4-Methylphenyl)-2-nitroethyl]-3-(4-methylphen-
ylamino)acrylate (1j)
Yield: 0.568 g (80%); white solid; mp 126–128 °C.
IR (KBr): 3298, 2950, 1673, 1617, 1545, 1445, 1372, 1304, 1200,
1151, 1051, 999, 948, 812 cm–1.
13C NMR (150 MHz, CDCl3): d = 168.9, 144.3, 137.9, 137.8, 133.2,
132.9, 130.3, 128.9, 128.8, 116.0, 96.3, 77.9, 51.1, 43.9, 20.7.
1H NMR (600 MHz, CDCl3): d = 10.0 (d, J = 12.6 Hz, 1 H, NH),
7.14 (br s, 4 H, ArH), 7.11 (d, J = 12.6 Hz, 1 H, CH), 7.07 (d, J =
MS: m/z (%) = 397.35 ([M + Na], 100).
Anal. Calcd for C19H19ClN2O4: C, 60.88; H, 5.11; N, 7.47. Found:
C, 60.67; H, 6.32; N, 7.29.
7.8 Hz, 2 H, ArH), 6.76 (d, J = 8.4 Hz, 2 H, ArH), 4.96 (dd, 3JHH
12.5 Hz, 2JHH = 7.8 Hz, 1 H, CH), 4.85 (dd, 3JHH = 12.5 Hz, 2JHH
=
=
8.4 Hz, 1 H, CH), 4.63 (t, J = 7.8 Hz, 1 H, CH), 3.74 (s, 3 H, OCH3),
2.32 (s, 3 H, CH3), 2.28 (s, 3 H, CH3).
13C NMR (150 MHz, CDCl3): d = 169.2, 144.3, 138.1, 137.0, 135.9,
132.6, 130.2, 129.5, 127.4, 115.9, 96.9, 78.3, 51.1, 43.9, 21.0, 20.7.
Methyl 2-[1-(4-Bromophenyl)-2-nitroethyl]-3-(4-methylphen-
ylamino)acrylate (1n)
Yield: 0.607 g (73%); white solid; mp 135–136 °C.
IR (KBr): 3298, 2951, 1673, 1614, 1548, 1517, 1485, 1445, 1370,
1304, 1228, 1196, 1150, 1072, 1003, 945, 870, 821, 784 cm–1.
MS: m/z (%) = 377.39 ([M + Na], 100).
Anal. Calcd for C20H20N2O4: C, 67.78; H, 6.26; N, 7.90. Found: C,
67.53; H, 6.47; N, 7.5.
1H NMR (600 MHz, CDCl3): d = 10.0 (d, J = 12.6 Hz, 1 H, NH),
7.46 (d, J = 8.4 Hz, 2 H, ArH), 7.15–7.11 (m, 3 H, ArH, CH), 7.09
(d, J = 8.4 Hz, 2 H, ArH), 6.79 (d, J = 7.8 Hz, 2 H, ArH), 4.96 (dd,
3JHH = 12.7 Hz, 2JHH = 7.8 Hz, 1 H, CH), 4.86 (dd, 3JHH = 12.7 Hz,
2JHH = 8.2 Hz, 1 H, CH), 4.56 (t, J = 7.8 Hz, 1 H, CH), 3.73 (s, 3 H,
OCH3), 3.29 (s, 3 H, CH3).
Methyl 2-[1-(4-Methoxyphenyl)-2-nitroethyl]-3-(4-methylphe-
nylamino)acrylate (1k)
Yield: 0.614 g (83%); white solid; mp 120–122 °C.
IR (KBr): 3296, 2951, 1670, 1615, 1546, 1513, 1449, 1371, 1303,
1235, 1199, 1152, 1032, 848, 826, 778 cm–1.
13C NMR (150 MHz, CDCl3): d = 168.9, 144.3, 138.2, 137.9, 133.0,
131.9, 130.3, 129.2, 121.2, 116.0, 96.2, 77.9, 51.1, 44.0, 20.7.
1H NMR (600 MHz, CDCl3): d = 9.99 (d, J = 11.4 Hz, 1 H, NH),
7.18 (d, J = 7.2 Hz, 2 H, ArH), 7.10–7.06 (m, 3 H, ArH, CH), 6.87
(d, J = 7.2 Hz, 2 H, ArH), 6.76 (d, J = 7.2 Hz, 2 H, ArH), 4.96–4.93
(m, 1 H, CH), 4.84–4.81 (m, 1 H, CH), 4.62 (t, J = 7.2 Hz, 1 H, CH),
3.78 (s, 3 H, OCH3), 3.75 (s, 3 H, OCH3), 2.27 (s, 3 H, CH3).
13C NMR (150 MHz, CDCl3): d = 169.2, 158.8, 144.2, 138.1, 132.6,
130.8, 130.2, 128.7, 128.4, 115.8, 115.7, 114.4, 114.2, 97.0, 78.4,
55.3, 51.1, 43.6, 20.7.
MS: m/z (%) = 441.04 ([M + Na], 100).
Anal. Calcd for C19H19BrN2O4: C, 54.43; H, 4.57; N, 6.68. Found:
C, 54.30; H, 4.71; N, 6.35.
Methyl 2-[1-(4-Methylphenyl)-2-nitroethyl)-3-(3-methylphen-
ylamino)acrylate (1o)
Yield: 0.540 g (76%); white solid; mp 105–106 °C.
IR (KBr): 3300, 2919, 1673, 1619, 1586, 1546, 1500, 1439, 1368,
1307, 1208, 1151, 997, 950, 828, 776 cm–1.
MS: m/z (%) = 393.22 ([M + Na], 100).
Anal. Calcd for C20H20N2O5: C, 64.85; H, 5.99; N, 7.56. Found: C,
64.79; H, 6.27; N, 7.44.
1H NMR (600 MHz, CDCl3): d = 10.00 (d, J = 12.0 Hz, 1 H, NH),
7.17–7.14 (m, 6 H, ArH, CH), 6.81 (d, J = 7.2 Hz, 1 H, =CH), 6.69–
6.66 (m, 2 H, ArH), 4.97 (dd, 3JHH = 12.5 Hz, 2JHH = 7.9 Hz, 1 H,
CH), 4.86 (dd, 3JHH = 12.5 Hz, 2JHH = 8.3 Hz, 1 H, CH), 4.62 (t, J =
7.8 Hz, 1 H, CH), 3.74 (s, 3 H, OCH3), 2.32 (s, 3 H, CH3), 2.30 (s,
3 H, CH3).
Methyl 2-[1-(3-Methoxyphenyl)-2-nitroethyl)-3-(4-methylphe-
nylamino)acrylate (1l)
Yield: 0.589 g (80%); white solid; mp 98–100 °C.
IR (KBr): 2947, 1674, 1617, 1546, 1441, 1378, 1304, 1221, 1125,
1051, 1007, 937, 862, 777 cm–1.
13C NMR (150 MHz, CDCl3): d = 169.1, 143.9, 140.4, 139.7, 137.0,
135.9, 129.5, 129.4, 127.4, 123.9, 116.6, 112.8, 97.3, 78.3, 51.1,
44.0, 21.5, 21.0.
1H NMR (600 MHz, CDCl3): d = 10.01 (d, J = 12.6 Hz, 1 H, NH),
7.27–7.25 (m, 1 H, ArH), 7.12 (d, J = 12.6 Hz, 1 H, CH), 7.08 (d,
J = 8.4 Hz, 2 H, ArH), 6.85 (d, J = 7.8 Hz, 1 H, ArH), 6.80 (br s, 2
H, ArH), 6.77 (d, J = 8.4 Hz, 2 H, ArH), 4.96 (dd, 3JHH = 12.7 Hz,
2JHH = 7.8 Hz, 1 H, CH), 4.88 (dd, 3JHH = 12.7 Hz, 2JHH = 8.3 Hz, 1
H, CH), 4.64 (t, J = 7.8 Hz, 1 H, CH), 3.79 (s, 3 H, OCH3), 3.75 (s,
3 H, OCH3), 2.28 (s, 3 H, CH3).
13C NMR (150 MHz, CDCl3): d = 169.1, 159.9, 144.4, 140.6, 138.0,
132.7, 130.2, 129.8, 119.6, 115.9, 113.9, 112.4, 96.6, 78.1, 55.3,
51.1, 44.2, 20.7.
MS: m/z (%) = 377.33 ([M + Na], 100).
Anal. Calcd for C20H22N2O4: C, 67.78; H, 6.26; N, 7.90. Found: C,
67.44; H, 6.50; N, 7.65.
Methyl 2-[1-(4-Methylphenyl)-2-nitroethyl)-3-(4-chlorophen-
ylamino)acrylate (1p)
Yield: 0.537 g (72%); white solid; mp 142–144 °C.
IR (KBr): 3304, 2950, 1675, 1624, 1548, 1502, 1452, 1372, 1317,
1227, 1198, 1152, 1001, 944, 823 cm–1.
Synthesis 2012, 44, 1069–1073
© Thieme Stuttgart · New York

PAPER
2-(1-Aryl-2-nitroethyl)-3-arylaminoacrylates
1073
1H NMR (600 MHz, CDCl3): d = 10.06 (d, J = 12.0 Hz, 1 H, NH),
7.23 (d, J = 8.4 Hz, 2 H, ArH), 7.14 (br s, 4 H, ArH), 7.07 (d, J =
12.0 Hz, 1 H, CH), 6.78 (d, J = 8.4 Hz, 2 H, ArH), 4.98–4.95 (m, 1
H, CH), 4.87–4.83 (m, 1 H, CH), 4.62 (t, J = 7.8 Hz, 1 H, CH), 3.75
(s, 3 H, OCH3), 2.33 (s, 3 H, CH3).
(4) (a) Vohra, R. K.; Bruneau, C.; Renaud, J. Adv. Synth. Catal.
2006, 348, 2571. (b) Kumar, A.; Maurya, R. A. Tetrahedron
2008, 64, 3477. (c) Moreau, J.; Duboc, A.; Hubert, C.;
Hurvois, J.-P.; Renaud, J. L. Tetrahedron Lett. 2007, 48,
8647. (d) Sirijindalert, H.; Hansuthirakul, K.;
Rashatasakhon, P.; Sukwattanasinitt, M.; Ajavakom, A.
Tetrahedron 2010, 66, 5161.
13C NMR (150 MHz, CDCl3): d = 169.1, 143.4, 139.1, 135.5, 129.7,
129.6, 127.9, 127.4, 116.9, 98.4, 78.2, 51.3, 43.9, 21.0.
(5) (a) Rechsteiner, B.; Texier-Boullet, F.; Hamelin, J.
Tetrahedron Lett. 1993, 34, 5071. (b) Valduga, C. J.;
Squizani, A.; Braibante, H. S.; Braibante, M. E. F. Synthesis
1998, 1019. (c) Arcadi, A.; Bianchi, G.; Di Giuseppe, S.;
Marinelli, F. Green Chem. 2003, 64. (d) Khosropour, A. R.;
Khodaei, M. M.; Kookhazadeh, M. Tetrahedron Lett. 2004,
45, 1725.
MS: m/z (%) = 397.59 ([M + Na], 100).
Anal. Calcd for C19H19ClN2O4: C, 60.88; H, 5.11; N, 7.47. Found:
C, 60.73; H, 5.45; N, 7.50.
Methyl 2-[1-(4-tert-Butylphenyl)-2-nitroethyl]-3-(4-chlorophe-
nylamino)acrylate (1q)
(6) (a) Glotova, T.; Dvorko, M.; Ushakov, I.; Chipanina, N.;
Kazheva, O.; Chekhlov, A.; Dyachenko, O.; Gusarova, N.;
Trofimov, B. Tetrahedron 2009, 65, 9814. (b) Ziyaei-
Halimehjani, A.; Saidi, M. R. Tetrahedron Lett. 2008, 49,
1244. (c) Li, X.; Wang, J. Y.; Yu, W.; Wu, L. M.
Tetrahedron 2009, 65, 1140. (d) Yavari, I.; Bayat, M. J.;
Sirouspour, M.; Souri, S. Tetrahedron 2010, 66 , 7995.
(7) (a) Nguyen, T. B.; Martel, A.; Dhal, R.; Dujardin, G. Org.
Lett. 2008, 10, 4493. (b) Fan, M. Q.; Yan, Z. Y.; Liu, W. M.;
Liang, Y. M. J. Org. Chem. 2005, 70, 8204. (c) Naidu, B.
N.; Sorenson, M. E. Org. Lett. 2005, 7, 1391. (d) Madhav,
B.; Murthy, S. N.; Rao, K. R.; Venkata, Y.; Nageswar, D.
Helv. Chim. Acta 2010, 93, 257.
(8) (a) Srikrishna, A.; Sridharan, M.; Prasad, K. R. Tetrahedron
Lett. 2010, 51, 3651. (b) Bezenšek, J.; Koleša, T.; Grošelj,
U.; Wagger, J.; Stare, K.; Meden, A.; Svete, J.; Stanovnik, B.
Tetrahedron Lett. 2010, 51, 3392. (c) Alizadeh, A.;
Rostamnia, S.; Hosseinpour, N. Tetrahedron Lett. 2009, 50,
1533.
Yield: 0.645 g (78%); white solid; mp 148–150 °C.
IR (KBr): 3404, 3289, 2960, 1669, 1626, 1551, 1500, 1438, 1371,
1227, 1151, 1104, 1005, 940, 823, 786 cm–1.
1H NMR (600 MHz, CDCl3): d = 10.05 (d, J = 12.6 Hz, 1 H, NH),
7.35 (d, J = 8.4 Hz, 2 H, ArH), 7.22 (d, J = 8.4 Hz, 2 H, ArH), 7.18
(d, J = 8.4 Hz, 2 H, ArH), 7.07 (d, J = 12.0 Hz, 1 H, CH), 6.78 (d,
J = 8.4 Hz, 2 H, ArH), 4.99 (dd, 3JHH = 12.5 Hz, 2JHH = 8.2 Hz, 1 H,
CH), 4.88 (dd, 3JHH = 12.5 Hz, 2JHH = 7.9 Hz, 1 H, CH), 4.62 (t, J =
7.8 Hz, 1 H, CH), 3.75 (s, 3 H, OCH3), 1.30 (s, 9 H, CH3).
13C NMR (150 MHz, CDCl3): d = 169.1, 150.4, 143.4, 139.1, 135.6,
129.7, 127.9, 127.2, 125.8, 116.9, 98.4, 78.1, 51.2, 44.0, 34.5, 31.3.
MS: m/z (%) = 439.36 ([M + Na], 100).
Anal. Calcd for C22H25ClN2O4: C, 63.38; H, 6.04; N, 6.72. Found:
C, 63.27; H, 6.51; N, 6.49.
Acknowledgment
(9) (a) Cao, H.; Jiang, H. F.; Qi, C. R.; Yao, W. J.; Chen, H. J.
Tetrahedron Lett. 2009, 50, 1209. (b) Liu, W. B.; Jiang, H.
F.; Zhu, S. F.; Wang, W. Tetrahedron 2009, 65, 7985.
(c) Jiang, H. F.; Li, J. H.; Chen, Z. W. Tetrahedron 2010, 66,
9721. (d) Zhu, Q.; Jiang, H. F.; Li, J.; Liu, S.; Xia, C.; Zhang,
M. J. Comb. Chem. 2009, 11, 685.
This work was financially supported by the National Natural Sci-
ence Foundation of China (Grant No. 20972132) and the Priority
Academic Program Development of Jiangsu Higher Education In-
stitutions.
(10) (a) Sun, J.; Xia, E. Y.; Wu, Q.; Yan, C. G. Org. Lett. 2010,
12, 3678. (b) Sun, J.; Wu, Q.; Xia, E. Y.; Yan, C. G. Eur. J.
Org. Chem. 2011, 2981. (c) Sun, J.; Xia, E. Y.; Wu, Q.; Yan,
C. G. ACS Comb. Sci. 2011, 13, 421. (d) Sun, J.; Sun, Y.;
Xia, E. Y.; Yan, C. G. ACS Comb. Sci. 2011, 13, 436.
(11) Ghabraie, E.; Balalaie, S.; Bararjanian, M.; Bijanzadeh, H.
R.; Rominger, F. Tetrahedron 2011, 67, 5415.
(12) Gomez Sanchez, A.; Mancera, M.; Caballero, F. J.;
Bellanato, J. Anal. Quim. Ser. C 1983, 79, 175; Chem. Abstr.
1985, 102, 95485.
(13) Single crystal data for compounds 1d (CCDC 827899) and
1g (CCDC 827896) have been deposited at the Cambridge
Crystallographic Data Center. These data can be obtained
free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html
[or from the Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax:
References
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© Thieme Stuttgart · New York
Synthesis 2012, 44, 1069–1073