Microwave-assisted one pot synthesis of N-substitued 2-methyl-1H-pyrrole-3-carboxylate derivatives without catalyst and solvent

Article abstract of DOI:10.3987/COM-15-13340

An efficient one-pot synthetic method for the N-substituted 2-methyl-1H-pyrrole-3-carboxylate derivatives has been accomplished via a microwave irradiation MCRs of various α-bromoacetophenone, amines, and ethyl acetoacetate without any solvent and catalys

Full text of DOI:10.3987/COM-15-13340

HETEROCYCLES, Vol. 91, No. 12, 2015
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HETEROCYCLES, Vol. 91, No. 12, 2015, pp. 2367 - 2376. © 2015 The Japan Institute of Heterocyclic Chemistry
Received, 13th October, 2015, Accepted, 24th November, 2015, Published online, 2nd December, 2015
DOI: 10.3987/COM-15-13340
MICROWAVE-ASSISTED ONE POT SYNTHESIS OF N-SUBSTITUED
2-METHYL-1H-PYRROLE-3-CARBOXYLATE DERIVATIVES
WITHOUT CATALYST AND SOLVENT
Wei Kan, Tao Jing, Xiao-hong Zhang, Yong-jie Zheng, Lin Chen, and Bing
Zhao *
Chemistry and Chemical Engineering Institute, Qiqihar University, Qiqihar
China. e-mail:zhao_submit@aliyun.com
Abstract – An efficient one-pot synthetic method for the N-substituted
2-methyl-1H-pyrrole-3-carboxylate derivatives has been accomplished via a
microwave irradiation MCRs of various α-bromoacetophenone, amines, and ethyl
acetoacetate without any solvent and catalyst. This approach provides a
convenient one pot method for the synthesis of N-substituted
2-methyl-1H-pyrrole-3-carboxylate derivatives.
Green chemistry has come to the forefront of current chemical research to exploit efficient, sustainable,
and environmentally benign synthetic methodologies and inexpensive and environmentally friendly
reagents.1,2 Growing environmental concern in green chemistry has turned the great interest into
multicomponent reactions (MCRs) as the new direction in organic chemistry,3 multicomponent reactions
have been widely utilized in medicinal synthesis and combinatorial chemistry because of their simplicity,
advanced selectivity, high efficiency and good yield over conventional chemical reactions.4 Beside these,
microwave assisted organic synthesis (MAOS)5 is particularly welcome in the chemical and organic
synthesis by reducing reaction times, heightening product yields and increasing product purities.
The last decade has witnessed the synthesis of heterocycles continuing to attract the attentions in
medicinal chemistry and in organic synthesis, considerable efforts have been devoted to the synthesis of
this type of compounds.6 With a privileged heterocyclic entity, pyrrole derivatives have displayed an
important role in composition of biologically active compounds,7 functional materials,8 and medicinal
chemistry.9 Also, there are varieties of approaches to the substituted pyrrole derivatives, including the
classical Knorr, Paal–Knorr and Hantzsch reactions. Accordingly, many of diversities of pyrroles have
been reported. For example, 1,2-diaryl(heteroaryl)pyrroles and -3-methylpyrroles derivatives were
prepared in a two-step procedure from N-allylbenzotriazoles via intramolecular oxidative cyclization in

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HETEROCYCLES, Vol. 91, No. 12, 2015
the presence of Pd(II) catalyst;10 Simple synthesis of substituted pyrroles using iodine-catalyst had been
accomplished with excellent yields by Banik.11 Recently, Nikhil developed a three-component system to
synthesize pyrrole derivatives from corresponding amines and nitrostyrenes using
(diacetoxyiodo)benzene in ethanol.12
However, there are some flaws in the existing synthetic methodologies for the substituted pyrrole
derivatives. Traditional multistep synthesis is not straightforward and the overall yields remained lower;
although few MCRs strategies had been applied in the synthesis of pyrrole derivatives recently,13
complicated and metal catalysts were over-used in most of these methods which could lead to the
environment problems to some extent; the preparation of N-substituted pyrroles still suffered from
limitations.
In the context of our current research into MCRs based on the use of β-dicarbonyl building blocks for the
synthesis of heterocycles, a new multicomponent strategy by Hantzsch synthesis of pyrroles were
considered, which could overcome some shortcomings as a general synthetic method. We also wished to
describe a new more simple protocol for an environment-friendly, rapid, and convenient synthesis.
Therefore, the way of microwave irradiation was introduced in order to improve efficiency.
Table 1. Optimization of reaction condition for the synthesis of ethyl 2-methyl-1,5-diphenyl-1H-
pyrrole-3-carboxylate 4a
OEt
O
O
R2
O
O
R1
MW
R3 NH2
+
+
Br
N
O
R1
R2
R3
2
1
3
4
Molar Ratio
(α-bromoacetophenone
/aniline/ ethyl
Power
(W)
Yielda
(%)
Entry
Solvent
Time
acetoacetate)
b
1
2
3
4
5
6
7
8
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.0
1.0 : 1.0 : 1.0
1.0 : 1.0 : 2.0
1.0 : 1.0 : 2.5
1.0 : 1.0 : 2.5
1.0 : 1.0 : 2.5
acetic acid
acetic acid
acetic acid
acetic acid
acetic acid
acetic acid
acetic acid
48 h
ü
20
62
65
76
81
85
77
87
45 min
30 min
15 min
15 min
15 min
15 min
15 min
150
300
500
500
500
600
500
c
ü
a Isolated yield.
b Refluxing reaction
c Without solvent
With this goal in mind, the studies were initiated by the reaction of a one-pot three component
condensation reaction of α-bromoacetophenone, aniline, and ethyl acetoacetate with conventional way in
refluxing acetic acid. After 48 hours of operation at refluxing, a new spot was observed by TLC though
both aniline and α-bromoacetophenone were not completely consumed. We managed to separate and

HETEROCYCLES, Vol. 91, No. 12, 2015
2369
obtain the ethyl 2-methyl-1,5-diphenyl-1H-pyrrole-3-carboxylate by the flash column chromatography
with the yield of 20% (Table 1, entry 1). Although the reaction yield was quite lower, we were so glad to
see that multi-substituted pyrrole, namely ethyl 2-methyl-1,5-diphenyl-1H-pyrrole-3-carboxylate, was
also accessible by employing commercially available 2-α-bromoacetophenone, aniline, and ethyl
acetoacetate as starting materials without any catalyst. This exciting result encouraged us to carry out
more efficient pattern into this reaction. Then the microwave irradiation was applied. Only after 15 min of
operation at frequency of 300 W, the 2-bromo-1-phenylethanone was completely consumed and the yield
was raised to 65% (Table 1, entry 3).
In search for an optimization of reaction conditions, the one-pot reaction for the three components of
α-bromoacetophenone, aniline, and ethyl acetoacetate as model reaction were studied and the results are
summarized in Table 1. According to our experience in using the ethyl acetoacetate,14 the amount of ethyl
acetoacetate should be slightly excessive in microwave reaction, which was verified by controlling the
amounts (Table 1, entries 4–6) to set the molar ratio for completion of the reaction. It was found that 2.5
equivalents of ethyl acetoacetate in presence of one equivalent of α-bromoacetophenone and one
equivalent of aniline offered short reaction time (15 min) and the better yields (76%, Table 1, entry 6).
Besides, the effect of different microwave power was evaluated by settings such as 150, 300, 500, and
600 W. It was observed that the lower the power, the longer the reaction time. If the microwave power
ran up to 600 W, the reaction mixture quickly became black hard lump which could prevent the reaction
further development and led to the lower yield. The result showed that the irradiation at 500 W gives
better result. Subsequently, we attempted to complete this reaction with the condition of free solvent.
Under the same reaction time, the yields of the products were found to be constant. Through these
experiments, a power at 500 W and a time of 15 min without solvent were the optimal conditions to
complete the reaction (Table 1, entry 8). Under these conditions, ethyl 2-methyl-1,5-diphenyl-
1H-pyrrole-3-carboxylate was obtained with good yields.
After optimizing the conditions, the scope and generality of this method were investigated by the reaction
of substituted α-bromoacetophenone, various types of amines and ethyl acetoacetate under
microwave-irradiation with free solvent. As shown in Table 2, our method could be adapted to the
preparation of pyrroles bearing the following types of substituents at nitrogen: aryl (compounds 4a–4l),
alkyl (compounds 4m–4o) and heterocyclic methyl (compounds 4p–4r). Especially, the compounds
4p–4r modified by furan moiety did not affect the stability of this type of pyrrole derivatives and we got
the clear spectrum for their characterizations. Furthermore, the scope of α-bromoacetophenone in this
Hantzsch reaction was much broader than the one described in the previous literature. According to the
literature,15 we prepared two substituted α-bromoacetophenone, namely 4-methyl-α-bromoacetophenone
and 3-bromo-4-methoxy-α-bromoacetophenone, respectively. We carried out similar reaction with

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various α-bromoacetophenone containing electron-withdrawing (Br) and electron-donating (Me)
functional groups but it did not show any remarkable differences in the yields of products and reaction
times. These successful results clearly indicate that the present protocol is also extendable to a wide
variety of substrates for both α-bromoacetophenones and amines. All structures of the products were
1
13
characterized and determined by the IR, H NMR, C NMR and elementary analysis. We could not get
the single-crystal for these N-substituted 2-methyl-1H-pyrrole-3-carboxylate derivatives because of their
lower melting points.
Table 2. Synthesized N-substituted 2-methyl-1H-pyrrole-3-carboxylate derivatives by a one-pot three
component condensation reaction a
Entry
1
R1
H
R2
H
R3
Product
4a
4b
4c
Yield b (%)
C6H5
87
80
85
85
82
81
81
82
83
76
88
79
84
82
80
79
81
83
2
H
H
4-ClC6H4
4-MeC6H4
4-MeOC6H4
C6H5
3
H
H
4
H
H
4d
4e
5
Me
Me
Me
Me
MeO
MeO
MeO
MeO
H
H
6
H
4-ClC6H4
4-MeC6H4
4-MeOC6H4
C6H5
4f
7
H
4g
4h
4i
8
H
9
Br
Br
Br
Br
H
10
11
12
13
14
15
16
17
18
4-ClC6H4
4-MeC6H4
4-MeOC6H4
n-Bu
4j
4k
4l
4m
4n
4o
4p
4q
4r
Me
MeO
H
H
n-Bu
Br
H
n-Bu
C4H3O-2-CH2
C4H3O-2-CH2
C4H3O-2-CH2
Me
MeO
H
Br
a
All reactions were carried out using α-bromoacetophenone (1.0 mmol), amine (1.0 mmol) and ethyl acetoacetate (2.5 mmol)
at 450 W under microwave irradiation without solvent.
b Isolated yield based on α-bromoacetophenone
EXPERIMENTAL
All melting points were estimated using a X4 melting apparatus in open capillaries. and are uncorrected.
IR spectra were determined as KBr disks with a Perkin-Elmer Spectrum one FT-IR. The 1H NMR spectra
were recorded using a Bruker AV400MHz spectrometer using CDCl3 as solvent and TMS as an internal
standard. The 13C NMR spectra were determined using TMS as an internal reference with a Bruker

HETEROCYCLES, Vol. 91, No. 12, 2015
2371
AV400MHz spectrometer operating at 100 MHz. Elemental analyses were performed on a Perkin-Elmer
240 microanalyser. TLC was carried out on a Merck Kieselgel GF254. Column chromatography was
performed using Merck Kieselgel 60 (0.075-0.15 mm). All of the organic solvents used in this study were
dried over appropriate drying agents and distilled prior to use.
Starting Materials. 4-Methyl-α-bromoacetophenone and 3-bromo-4-methoxy-α-bromoacetophenone
were prepared according to the literature.15 All other chemicals used in this study were commercially
available.
Typical Procedure for the Preparation of Products 4a-4r.
A
mixture of various
α-bromoacetophenones 1 (1 mmol), amines 2 (1 mmol), and ethyl acetoacetate 3 (2.5 mmol) was placed
in a pressurized microwave vial with snap on cap. The reaction mixture was subjected to microwave
irradiation for appropriate time at 500 W. After the completion of the reaction (as indicated by TLC) and
cooling to room temperature, the oil crude products were obtained and then purified by column
chromatography on silica gel using EtOAc/n-hexane to afford the pure compounds 4a-4r for analysis.
Ethyl 2-methyl-1,5-diphenyl-1H-pyrrole-3-carboxylate (4a): Yellow solid, 87% yield. IR (KBr) υ:
3092, 2980, 2927, 1685, 1380, 1281, 1202 cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.40–7.37 (m, 3H, ArH),
7.14–7.11 (m, 5H, ArH), 7.04–6.99 (m, 2H, ArH), 6.80 (s, 1H, ArH), 4.33 (q, J = 5.2 Hz, 2H, CH2), 2.41
13
(s, 3H, CH3), 1.38 (t, 3H, J = 5.0 Hz, CH3); C NMR (100 MHz, CDCl3) δ: 165.6, 138.1, 138.1, 133.9,
132.4, 129.2, 128.5, 128.2, 128.1, 128.0, 126.5, 112.8, 110.0, 59.5, 14.6, 12.5; Anal. Calcd for C20H19NO2:
C, 78.66; H, 6.27; N, 4.59%. Found: C, 78.50; H, 6.41; N, 4.68%.
Ethyl 1-(4-chlorophenyl)-2-methyl-5-phenyl-1H-pyrrole-3-carboxylate (4b): 80% yield. IR (KBr) υ:
3370, 2920, 1682, 1587, 1445, 1252, 1170, 1029 cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.35–7.31 (m, 2H,
ArH), 7.06–7.04 (m, 3H, ArH), 7.04 (d, J = 7.5 Hz, 2H, ArH), 7.02 (d, J = 7.5 Hz, 2H, ArH), 6.78 (s, 1H,
13
ArH), 4.32 (q, J = 5.0 Hz, 2H, CH2), 2.39 (s, 3H, CH3), 1.37 (t, J = 5.0 Hz, 3H, CH3); C NMR (100
MHz, CDCl3) δ: 165.4, 137.8, 136.6, 134.1, 133.8, 132.0, 129.7, 129.4, 128.2, 128.1, 126.7, 113.2, 110.2,
59.5, 14.5, 12.4; Anal. Calcd for C20H18ClNO2: C, 70.69; H, 5.34; N, 4.12%. Found: C, 70.52; H, 5.23; N,
4.19%.
Ethyl 2-methyl-5-phenyl-1-p-tolyl-1H-pyrrole-3-carboxylate (4c): 85% yield. IR (KBr) υ: 3372, 2923,
1682, 1589, 1441, 1320, 1249, 1170, 1019 cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.18 (m, 2H, ArH), 7.16
(m, 3H, ArH), 7.06 (d, 2H, J = 7.5 Hz, ArH), 7.02 (d, 2H, J = 7.5 Hz, ArH), 6.79 (s, 1H, ArH), 4.32 (q, J
= 5.0 Hz, 2H, CH2), 2.42 (s, 3H, CH3), 2.38 (s, 3H, CH3), 1.37 (t, 3 H, J = 5.0 Hz); 13C NMR (100 MHz,
CDCl3) δ: 165.6, 138.2, 138.1, 135.5, 133.9, 132.5, 130.1, 129.9, 129.8, 129.3, 128.2, 128.1, 127.9, 127.5,

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126.3, 126.2, 126.1, 120.9, 112.7, 109.9, 59.5, 21.1, 14.05, 12.60; Anal. Calcd for C21H21NO2: C, 78.97;
H, 6.63; N, 4.39%. Found: C, 79.10; H, 6.53; N, 4.56%.
Ethyl 1-(4-methoxyphenyl)-2-methyl-5-phenyl-1H-pyrrole-3-carboxylate (4d): 85% yield. IR (KBr) υ:
1
3375, 2925, 1680, 1600, 1443, 1325, 1250, 1170, 1024 cm–1. H NMR (400 MHz, CDCl3) δ: 7.16–7.12
(m, 3H, ArH), 7.06–7.04 (m, 4H, ArH), 6.93 (d, J = 7.5 Hz, 2H, ArH), 6.78 (s, 1H, ArH), 4.31 (q, J =
13
5.0 Hz, 2H, CH2), 3.83 (s, 3H, OCH3), 2.39 (s, 3H, CH3), 1.38 (t, J = 5.0 Hz, 3H, CH3); C NMR (100
MHz, CDCl3) δ: 165.6, 159.2, 138.3, 136.9, 135.6, 134.0, 132.5, 131.9, 130.8, 129.4, 129.2, 128.1, 128.0,
127.5, 126.4, 126.3, 126.2, 121.10, 112.6, 109.7, 59.4, 55.4, 14.6, 12.5; Anal. Calcd for C21H21NO3: C,
75.20; H, 6.31; N, 4.18%. Found: C, 75.36; H, 6.18; N, 4.34%.
Ethyl 2-methyl-1-phenyl-5-p-tolyl-1H-pyrrole-3-carboxylate (4e): 82% yield. IR (KBr) υ: 3075, 2925,
1
1691, 1488, 1310, 1194, 848, 791 cm–1. H NMR (400 MHz, CDCl3) δ: 7.39–7.36 (m, 3H, ArH),
7.14–7.11 (m, 2H, ArH), 6.88 (d, J = 7.5 Hz, 4H, ArH), 6.73 (s, 1H, ArH), 4.33 (q, 2H, J = 5.0 Hz, CH2),
13
3.83 (s, 3H, OCH3), 2.39 (s, 3H, CH3), 2.25 (s, 3H, CH3), 1.37 (t, J = 5.0 Hz, 3H, CH3); C NMR (100
MHz, CDCl3) δ: 165.6, 138.2, 138.1, 135.4, 133.8, 132.4, 130.1, 129.8, 129.7, 129.2, 128.1, 128.0, 127.9,
127.5, 126.3, 126.1, 126.1, 120.8, 112.6, 109.8, 59.4, 22.6, 14.5, 12.6; Anal. Calcd for C21H21NO2: C,
78.97; H, 6.63; N, 4.39%. Found: C, 78.92; H, 6.57; N, 4.50%.
Ethyl 1-(4-chlorophenyl)-2-methyl-5-p-tolyl-1H-pyrrole-3-carboxylate (4f): 81% yield. IR (KBr) υ:
3377, 2927, 1682, 1600, 1449, 1327, 1252, 1175, 1029 cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.37 (d, J =
7.2 Hz, 2H, ArH), 7.08 (d, J = 7.2 Hz, 2H, ArH), 6.98 (d, J = 7.2 Hz, 2H, ArH), 6.93 (d, J = 7.2 Hz, 2H,
ArH), 6.78 (s, 1H, ArH), 4.31 (q, J = 5.0 Hz, 2H, CH2), 2.39 (s, 3H, CH3), 2.27 (s, 3H, CH3), 1.37 (t, J =
5.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 165.5, 136.3, 133.4, 133.1, 129.3, 128.8, 128.3, 127.40,
111.8, 109.7, 59.2, 29.6, 14.5, 12.5; Anal. Calcd for C21H20ClNO2: C, 71.28; H, 5.70; N, 3.96%. Found: C,
71.45; H, 5.65; N, 4.04%.
Ethyl 2-methyl-1,5-di-p-tolyl-1H-pyrrole-3-carboxylate (4g): 81% yield. IR (KBr) υ: 3371, 2922, 1680,
1600, 1447, 1325, 1250, 1173, 1027cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.17 (d, J = 7.2 Hz, 2H, ArH),
7.01 (d, J = 7.2 Hz, 2H, ArH), 6.94 (d, J = 7.2 Hz, 4H, ArH), 6.74 (s, 1H, ArH), 4.32 (q, J = 5.0 Hz, 2H,
13
CH2), 2.42 (s, 3H, CH3), 2.38 (s, 3H, CH3), 2.25 (s, 3H, CH3), 1.37 (t, 3 H, J = 5.0 Hz, CH3); C NMR
(100 MHz, CDCl3) δ: 165.6, 138.0, 137.9, 136.0, 135.5, 133.9, 129.8, 129.7, 129.6, 129.0, 128.7, 128.2,
128.1, 127.9, 126.1, 112.5, 109.3, 59.4, 21.1, 21.0, 14.5, 12.4; Anal. Calcd for C22H23NO2: C, 79.25; H,
6.95; N, 4.20%. Found: C, 79.41; H, 6.79; N, 4.34%.
Ethyl 1-(4-methoxyphenyl)-2-methyl-5-p-tolyl-1H-pyrrole-3-carboxylate (4h): 82% yield. IR (KBr) υ:
3377, 2927, 1682, 1600, 1449, 1327, 1252, 1175, 1029 cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.04 (d, J =
7.2 Hz, 2H, ArH), 6.94 (d, J = 7.2 Hz, 4H, ArH), 6.88 (d, J = 7.2 Hz, 2H, ArH), 6.72 (s, 1H, ArH), 4.31

HETEROCYCLES, Vol. 91, No. 12, 2015
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(q, J = 5.0 Hz, 2H, CH2), 3.81 (s, 3H, OCH3), 2.36 (s, 3H, CH3), 2.25 (s, 3H, CH3), 1.36 (t, J = 5.0 Hz, 3H,
13
CH3); C NMR (100 MHz, CDCl3) δ: 165.6, 138.2, 137.8, 136.2, 134.0, 126.5, 129.4, 129.32, 129.1,
129.1, 128.7, 128.5, 128.3, 128.2, 128.0, 127.9, 126.3, 112.7, 109.5, 59.5, 21.1, 14.6, 12.5; Anal. Calcd
for C22H23NO3: C, 75.62; H, 6.63; N, 4.01%. Found: C, 75.77; H, 6.49; N, 4.12%.
Ethyl 5-(3-bromo-4-methoxyphenyl)-2-methyl-1-phenyl-1H-pyrrole-3-carboxylate (4i): 83% yield.
1
IR (KBr) υ: 2918, 1680, 1601, 1445, 1325, 1249, 1175, 1021 cm–1. H NMR (400 MHz, CDCl3) δ:
7.41–7.39 (m, 3H, ArH), 7.28 (s, 1H, ArH), 7.12 (d, J = 7.2 Hz, 2H, ArH), 6.85 (d, J = 7.2 Hz, 1H,
ArH), 6.72 (s, 1H, ArH), 6.63 (d, J = 7.2 Hz, 1H, ArH), 4.31 (q, J = 5.0 Hz, 2H, CH2), 3.81 (s, 3H, OCH3),
13
2.38 (s, 3H, CH3), 1.36 (t, J = 5.0 Hz, 3H, CH3); C NMR (100 MHz, CDCl3) δ: 165.5, 154.5, 138.0,
137.8, 133.0, 132.1, 129.3, 129.3, 128.5, 128.4, 128.1, 126.4, 126.3, 112.8, 111.3, 111.1, 109.7, 59.5, 56.1,
14.2, 12.5; Anal. Calcd for C21H20BrNO3: C, 60.88; H, 4.87; N, 3.38%. Found: C, 60.76; H, 5.01; N,
3.29%.
Ethyl 5-(3-bromo-4-methoxyphenyl)-1-(4-chlorophenyl)-2-methyl-1H-pyrrole-3-carboxylate (4j):
1
76% yield. IR (KBr) υ: 3367, 2926, 1680, 1598, 1324, 1250, 1172, 1027 cm–1. H NMR (400 MHz,
CDCl3) δ: 7.37 (d, J = 7.2 Hz, 2H, ArH), 7.32 (s, 1H, ArH), 7.05 (d, J = 7.2 Hz, 2H, ArH), 6.79 (d, J =
7.2 Hz, 1H, ArH), 6.71 (s, 1H, ArH), 6.65 (d, J = 7.2 Hz, 1H, ArH), 4.30 (q, J = 5.0 Hz, 2H, CH2), 3.82 (s,
3H, OCH3), 2.37 (s, 3H, CH3), 1.36 (t, J = 5.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ:
165.9 ,149.1, 134.9, 133.4, 131.1, 129.6, 129.4, 127.8, 127.5, 120.8, 120.7, 112.7, 106.8, 110.3, 60.9, 55.1,
14.1, 12.5; Anal. Calcd for C21H19BrClNO3S: C, 56.21; H, 4.27; N, 3.12%. Found: C, 56.39; H, 4.20; N,
3.21%.
Ethyl 5-(3-bromo-4-methoxyphenyl)-2-methyl-1-p-tolyl-1H-pyrrole-3-carboxylate (4k): 85% yield.
IR (KBr) υ: 3370, 2925, 1680, 1600, 1447, 1325, 1250, 1173, 1027 cm–1. 1H NMR (400 MHz, CDCl,) δ:
7.43 (d, J = 7.2 Hz, 2H, ArH), 7.34 (s, 1H, ArH), 7.01 (d, J = 7.2 Hz, 2H, ArH), 6.86 (d, J = 7.2 Hz, 1H,
ArH), 6.71 (s, 1H, ArH), 6.65 (d, J = 7.2 Hz, 1H, ArH), 4.31 (q, J = 5.0 Hz, 2H, CH2), 3.82 (s, 3H, OCH3),
2.37 (s, 3H, CH3), 2.25 (s, 3H, CH3), 1.36 (t, J = 5.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 165.5,
138.1, 138.0, 136.2, 135.1, 133.0, 129.2, 128.0, 124.6, 120.8, 112.6, 111.0, 110.5, 109.5, 59.4, 56.1, 21.0,
14.2, 12.4; Anal. Calcd for C22H22BrNO3: C, 61.69; H, 5.18; N, 3.27%. Found: C, 61.80; H, 5.11; N,
3.15%.
Ethyl 5-(3-bromo-4-methoxyphenyl)-1-(4-methoxyphenyl)-2-methyl-1H-pyrrole-3-carboxylate (4l):
79% yield. IR (KBr) υ: 3370, 2920, 1675, 1593, 1442, 1320, 1247, 1168, 1022 cm–1. 1H NMR (400 MHz,
CDCl3) δ: 7.41 (d, J = 7.2 Hz, 2H, ArH), 7.30 (s, 1H, ArH), 7.10 (d, J = 7.2 Hz, 2H, ArH), 6.93 (d, J =
7.2 Hz, 1H, ArH), 6.73 (s, 1H, ArH), 6.69 (d, J = 7.2 Hz, 1H, ArH), 4.31 (q, J = 5.0 Hz, 2H, CH2), 3.84 (s,
13
3H, OCH3), 3.82 (s, 3H, OCH3), 2.37 (s, 3H, CH3), 1.36 (t, J = 5.0 Hz, 3H, CH3); C NMR (100 MHz,

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CDCl3) δ: 165.6, 138.2, 137.2, 134.1, 132.2, 130.5, 129.2, 128.0, 127.5, 126.5, 124.5, 121.0, 114.7, 114.4,
112.5, 110.5, 109.4, 59.4, 56.1, 55.4, 14.2, 12.4; Anal. Calcd for C22H22NO4: C, 59.47; H, 4.99; N, 3.15%.
Found: C, 59.60; H, 5.09; N, 3.11%.
Ethyl 1-butyl-2-methyl-5-phenyl-1H-pyrrole-3-carboxylate (4m): 84% yield. IR (KBr) υ: 2980, 2927,
1685, 1380, 1281, 1202, 757cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.39 (d, J = 7.2 Hz, 2H, ArH), 7.28 (t, J
= 7.2 Hz, 3H, ArH), 6.53 (s, 1H, ArH), 4.26 (q, J = 5.0 Hz, 2H, CH2), 3.86–3.83 (m, 2H, CH2), 2.59 (s,
3H, CH3), 1.51–1.46 (m, 2H, CH2), 1.33 (t, J = 5.0 Hz, 3H, CH3), 1.17–1.11(m, 2H, CH2), 0.77 (t, J = 5.0
13
Hz, 3H, CH3); C NMR (100 MHz, CDCl3) δ: 165.5, 136.3, 133.4, 133.1, 129.3, 128.8, 128.3, 127.4,
111.8, 109.7, 59.2, 43.8, 32.7, 19.6, 14.5, 13.4, 11.5; Anal. Calcd for C18H23NO2: C, 75.76; H, 8.12; N,
4.91%. Found: C, 75.90; H, 8.27; N, 4.76%.
Ethyl 1-butyl-2-methyl-5-p-tolyl-1H-pyrrole-3-carboxylate (4n): 82% yield. IR (KBr) υ: 2983, 2924,
1685, 1380, 1280, 1200, 757cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.26–7.18 (m, 4H, ArH), 6.49 (s, 1H,
ArH), 4.26 (q, J = 5.0 Hz, 2H, CH2), 3.86–3.83 (m, 2H, CH2), 2.58 (s, 3H, CH3), 2.39 (s, 3H, CH3),
1.52–1.48 (m, 2H, CH2), 1.33 (t, J = 5.0 Hz, 3H, CH3), 1.18–1.12 (m, 2H, CH2), 0.80 (t, J = 5.0 Hz, 3H,
13
CH3); C NMR (100 MHz, CDCl3) δ: 165.5, 136.3, 133.4, 133.1, 129.3, 128.8, 128.3, 127.4, 111.8,
109.7, 59.2, 43.8, 32.7, 19.6, 14.5, 13.4, 11.5; Anal. Calcd for C19H25NO2: C, 76.22; H, 8.42; N, 4.68%.
Found: C, 76.08; H, 8.39; N, 4.76%.
Ethyl 5-(3-bromo-4-methoxyphenyl)-1-butyl-2-methyl-1H-pyrrole-3-carboxylate (4o): 80% yield. IR
(KBr) υ: 2984, 2930, 1687, 1384, 1285, 1207, 757cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.32 (s, 1H, ArH),
6.96 (d, J = 7.2 Hz, 1H, ArH), 6.73 (s, 1H, ArH), 6.69 (d, J = 7.2 Hz, 1H, ArH), 4.27 (q, J = 5.0 Hz, 2H,
CH2), 3.87–3.84 (m, 2H, CH2), 3.82 (s, 3H, OCH3), 2.38 (s, 3H, CH3), 1.52–1.48 (m, 2H, CH2), 1.33 (t, J
13
= 5.0 Hz, 3H, CH3), 1.18–1.12 (m, 2H, CH2), 0.80 (t, 3H, J = 5.0 Hz, CH3); C NMR (100 MHz,
CDCl3) δ: 165.5, 155.3, 136.3, 134.1, 131.6, 129.5, 127.0, 111.8, 111.6, 111.3, 109.8, 60.3, 59.3, 56.3,
43.8, 32.7, 19.7, 14.5, 13.8, 11.5; Anal. Calcd for C19H24BrNO3: C, 57.88; H, 6.14; N, 3.55%. Found: C,
57.79; H, 6.23; N, 3.47%.
Ethyl 1-(furan-2-yl)-2-methyl-5-phenyl-1H-pyrrole-3-carboxylate (4p): 79% yield. IR (KBr) υ: 3010,
2976, 2890, 1725, 1496, 1317, 1182, 850, 791cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.35 (d, J = 7.2 Hz,
1H, ArH), 7.34–7.25 (m, 5H, ArH), 6.60 (s, 1H, ArH), 6.28 (t, J = 5.2 Hz, 1H, ArH), 5.92 (d, J = 5.2 Hz,
1H, ArH), 4.29 (q, J = 5.0 Hz, 2H, CH2), 2.60 (s, 3H, CH3), 1.34 (t, 3H, J = 5.0 Hz, CH3); 13C NMR (100
MHz, CDCl3) δ: 197.7, 157.3, 147.6, 140.9, 137.6, 136.6, 133.4, 132.9, 128.8, 128.6, 128.1, 127.9, 113.5,
107.8, 51.8, 45.2, 21.5; Anal. Calcd for C18H17NO3: C, 73.20; H, 5.80; N, 4.74%. Found: C, 73.14; H,
5.85; N, 4.80%.

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Ethyl 1-(furan-2-yl)-2-methyl-5-p-tolyl-1H-pyrrole-3-carboxylate (4q): 81% yield. IR (KBr) υ: 3071,
2994, 2928, 1724, 1495, 1316, 1181, 848, 792cm–1. 1H NMR (400 MHz, CDCl3) δ: 7.33 (d, J = 7.2 Hz,
1H, ArH), 7.25 (d, J = 7.2 Hz, 2H, ArH), 7.18 (d, J = 7.2 Hz, 2H, ArH), 6.56 (s, 1H, ArH), 6.28 (t, J = 5.2
Hz, 1H, ArH), 5.93 (d, J = 5.2 Hz, 1H, ArH), 4.29 (q, J = 5.0 Hz, 2H, CH2), 2.59 (s, 3H, CH3), 2.37 (s,
13
3H, CH3), 1.34 (t, J = 5.0 Hz, 3H, CH3); C NMR (100 MHz, CDCl3) δ: 165.5, 150.5, 142.2, 137.4,
136.8, 133.9, 130.8, 129.5, 129.3, 129.1, 128.8, 128.6, 112.3, 110.3, 109.4, 107.4, 59.3, 41.6, 21.1, 14.5,
11.4; Anal. Calcd for C19H19NO3: C, 73.77; H, 6.19; N, 4.53%. Found: C, 73.90; H, 6.03; N, 4.46%.
Ethyl 1-(furan-2-yl)-2-methyl-5-phenyl-1H-pyrrole-3-carboxylate (4r): 83% yield. IR (KBr) υ: 3059,
1
2994, 2928, 1723, 1494, 1315, 1180, 848, 791cm–1. H NMR (400 MHz, CDCl3) δ: 7.55 (s, 1H, ArH),
7.35 (d, J = 7.2 Hz, 1H, ArH), 7.26 (d, J = 7.2 Hz, 1H, ArH), 6.89 (d, J = 7.2 Hz, 1H, ArH), 6.55 (s, 1H,
ArH), 6.30 (t, J = 5.2 Hz, 1H, ArH), 5.97 (d, J = 5.2 Hz, 1H, ArH), 4.29 (q, J = 5.0 Hz, 2H, CH2), 3.92 (s,
3H, CH3), 2.60 (s, 3H, CH3), 1.34 (t, J = 5.0 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 165.4, 155.5,
150.2, 142.4, 137.0, 134.4, 132.1, 129.6, 126.3, 112.4, 111.5, 110.4, 109.9, 107.7, 59.4, 56.3, 41.6, 14.5,
11.5; Anal. Calcd for C19H18BrNO4: C, 56.45; H, 4.49; N, 3.46%. Found: C, 56.39; H, 4.54; N, 3.61%.
ACKNOWLEDGEMENTS
This work was supported by the Programs for Education Department of Heilongjiang Province (no.
12541862) and New Century Excellent Talents in Heilongjiang Provincial University (1252-NECT-022)
and National Natural Science Foundation of China (21506106).
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