Triethylammonium hydrogen sulfate as a catalyst for the preparation of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-one derivatives

Article abstract of DOI:10.3184/174751911X13191347034936

Triethylammonium hydrogen sulfate [Et₃NH][HSO₄]) has been used as an efficient acidic ionic liquid catalyst for the preparation of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones at room temperature. The present methodology offers the

Full text of DOI:10.3184/174751911X13191347034936

634 RESEARCH PAPER
NOVEMBER, 634–636
JOURNAL OF CHEMICAL RESEARCH 2011
Triethylammonium hydrogen sulfate as a catalyst for the preparation of
1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-one derivatives
Mohammad Reza Mohammad Shafiee, Batool Hojati Najafabadi and Majid Ghashang*
Department of Chemistry, Faculty of Sciences, Islamic Azad University – Najafabad Branch, Najafabad, PO Box 517, Esfahan, Iran
Triethylammonium hydrogen sulfate [Et3NH][HSO4]) has been used as an efficient acidic ionic liquid catalyst for the
preparation of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones at room temperature. The present methodology offers
the advantages of good yields, a simple procedure, shorter reaction times and mild condition. The products were
purified without resorting to chromatography.
Keywords: 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-one, γ-lactam, ionic liquids, triethylammonium hydrogen sulfate catalyst,
green chemistry
In the context of organic synthesis, the primary objective of
green chemistry is to introduce different reaction conditions
that can form a basis for the development of more sustainable
organic synthesis.1,2 Ionic liquids have recently gained recog-
nition as possible environmentally safe alternatives to volatile
organic catalysts. They have many advantages such as high
efficiency, easy separation and purification, and mild reaction
conditions and can benefit the environment as well as indus-
try.3,4 Ionic liquids have been applied in many reactions as
catalysts. In addition, the ionic liquid catalyst can be easily
recovered and recycled without the loss of activity several
times. Therefore, attention is focused on organic reactions
promoted by ionic liquids.3,4
Compounds with a pyrrolidinone ring system have many
pharmacological properties and play important roles in
biochemical processes. In addition, pyrrolidinones are
important precursors of biologically active compounds in
organic synthesis and offer major synthetic opportunities for
the synthesis of biological and pharmaceutical compounds.5–7
Thus new approaches to the construction of 1,5-diaryl-3-
(arylamino)-1H-pyrrol-2(5H)-one derivatives are required.
Previously routes to 1,5-diaryl-3-(arylamino)-1H-pyrrol-
2(5H)-ones involve two-component condensation of amines
with pyrrolidine-2,3-diones8 and β,γ-unsaturated α-oxo esters9
or tri-component reaction of amines, aldehydes and pyruvate
in the presence of acidic catalysts such as H2SO410 and thiourea
and phosphoric acid analogues.11 However, homogeneous
liquid acid catalysts suffers from several disadvantages such as
high toxicity and also difficulty in separation and recovery.
Therefore replacement of these conventional acids by non-
toxic brønsted acidic ionic liquids is desirable to decrease
waste production.
pyruvate to form 3-(4-methoxyphenylamino)-1-(4-methoxy-
phenyl)-5-phenyl-1H-pyrrol-2(5H)-one was examined in the
presence of a number of Lewis and Brønsted acids. Among
various catalysts examined, triethylammonium hydrogen
sulfate exhibited the best catalytic activity (entry 15). Other
ionic liquids also gave the desired product in moderate to good
yields (entries 12–14), while, Lewis or Brønsted acids were
not as effective as the ionic liquids in the present transforma-
tion (entries 1–11). Under the standard conditions, no reaction
was observed in the absence of catalyst. This shows that the
catalyst was essential for the formation of the product. These
investigations into the impact of the counterion showed that
triethylammonium hydrogen sulfate was the most efficient
promoter for these conversions among the acidic catalysts
which were tested. The results are summarised in Table 1.
To find the optimum reaction conditions, the reaction was
carried out using different solvents (Table 2, entries 1–7) or
solvent-free condition (Table 2, entry 8). Among the solvents
screened, n-hexane was found to be the best in terms of
reaction times and yields (Table 2, entry 1).
To find the optimum amount of triethylammonium hydro-
gen sulfate, the reaction was carried out with varying amount
of the catalyst (Table 2, entries 9–11). Maximum yield was
obtained when 1 mmol of catalyst was used (Table 2, entry 1).
Further increase in the amount of triethylammonium hydrogen
sulfate did not have any significant effect on the yield of the
product. The results are summarised in Table 2.
The scope and efficiency of these procedures were then
explored in the synthesis of a wide variety of substituted
1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones (Scheme 1,
Table 3).
The overall aim of this project was to develop an efficient
protocol for the synthesis and easy purification of 1,5-diaryl-3-
(arylamino)-1H-pyrrol-2(5H)-ones by the cyclo-condensation
reaction of aldehydes, aryl amines and ethyl pyruvate in the
presence of triethylammonium hydrogen sulfate as an efficient
acidic ionic liquid catalyst.
As expected, this reaction proceeded smoothly and the
desired products were obtained in good yields. A series of
aromatic aldehydes and amines were investigated (Table 3,
entries 1–18). In all cases, aromatic aldehydes containing
electron-donating groups required shorter time and gave higher
yields than those with electron-withdrawing groups. Our
results show that aliphatic aldehydes reacted with 4-methyl-
aniline, and ethyl pyruvate successfully in good yields
(Table 3, entry 15). However, the use of an aliphatic amine did
not give any product (Table 3, entry 19).
Results and discussion
As a preliminary reaction, the catalytic of three-component
condensation of benzaldehyde, 4-methoxyaniline and ethyl
Scheme 1 Preparation of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-one derivatives.
* Correspondent. E-mail: ghashangmajid@gmail.com

JOURNAL OF CHEMICAL RESEARCH 2011 635
Scheme 2 Preparation of 3-(4-methoxyphenylamino)-1-(4-methoxyphenyl)-5-phenyl-1H-pyrrol-2(5H)-one.
Table 1 Optimization of the reaction conditions in the
synthesis of 3
corresponding products in good yields. The present methodol-
ogy offers several advantages such as good yields, simple pro-
cedure, shorter reaction times and milder conditions whilst the
products were purified without resorting to chromatography.
Entry Catalyst
Yield
/%a
1
2
SiO2-H2SO4 (solvent-free, 0.05 g, 100 °C)
15
–
10
12
–
Experimental
SiO2-FeCl3 (solvent-free, 0.05 g, 100 °C)
Al(H2PO4)3 (solvent-free, 0.05 g, 100 °C)
Al(HSO4)3 (solvent-free, 0.05 g, 100 °C)
ZnO (solvent-free, 0.1 mmol, 100 °C)
FeCl3.6H2O (solvent-free, 0.1 mmol, 100 °C)
AlCl3
All reagents were purchased from Merck and Aldrich and were used
without further purification. All yields refer to isolated products after
purification. The NMR spectra were recorded on a Bruker Avance
DPX 400 MHz instrument. The spectra were measured in DMSO-d6
relative to TMS (0.00 ppm). IR spectra were recorded on a Perkin
Elmer 781 spectrophotometer. Elemental analysis was performed on a
Heraeus CHN–O–Rapid analyser. Melting points were determined in
open capillaries with a BUCHI 510 melting point apparatus. TLC was
performed on silica gel polygram SIL G/UV 254 plates.
3
4
5
6
–
b
7
–
b
8
MgCl2
ZnCl2
–
b
9
–
10
11
12
13
14
15
16
SiO2-HClO4 (solvent-free, 0.05 g, 100 °C)
SiO2-H3PO4 (solvent-free, 0.05 g, 100 °C)
Triethylammonium hydrogenchloride (Et3NHCl)
9
14
25b
Triethylammonium trifluoroacetate (Et3NHOOCCF3) 35b
Triethylammonium methanesulfonate (Et3NHO3SCH3) 40b
General procedure
Triethylammonium hydrogen sulfate (1 mmol) as catalyst was added
to a mixture of aldehyde (1 mmol), aromatic amine (2 mmol) and
ethyl pyruvate (1.5 mmol) in n-hexane (5 mL). The mixture was
stirred for the appropriate time at room temperature. The progress of
the reaction was monitored by TLC. After completion of the reaction,
the mixture filtered and the product was washed with diethyl ether to
afford the pure product.
Triethylammonium hydrogen sulfate (Et3NHHSO4) 46b
b
–
–
a Isolated yield.
bReaction condition: room temperature, EtOH as solvent (5 ml),
reaction time: 120 min.
3-(4-methoxyphenylamino)-1-(4-methoxyphenyl)-5-o-tolyl-1H-pyrrol-
2(5H)-one (Table 3, entry 6): M.p. 195–198 °C, 1H NMR (400 MHz,
CDCl3): 2.45 (s, 3H), 3.77 (s, 3H), 3.81 (s, 3H), 5.88 (s, 1H), 5.95 (d,
J = 2.4 Hz, 1H), 6.52 (s, 1H), 6.84 (d, J = 8.8, 2H), 6.88 (d, J = 9.2 Hz,
2H), 7.05–7.16 (m, 6H), 7.41 (d, J = 8.8 Hz, 2H); 13C NMR
(100 MHz, CDCl3): δ = 19.1, 55.4, 55.6, 61.4, 105.0, 114.2, 114.7,
118.5, 118.7, 123.1, 126.8, 127.7, 130.6, 131.0, 133.3, 134.9, 135.3,
135.5, 154.4, 156.8, 167.3 ppm; IR (KBr): 3322, 3052, 3005, 2947,
2928, 1647, 1655, 1591, 1536, 1512, 1461, 1439, 1247, 1181, 1123,
1090, 1036, 920, 866, 818, 777.cm−1; Found: C, 75.06; H, 6.11; N,
7.05 C25H24N2O3; requires: C, 74.98; H, 6.04; N, 7.00%.
Table 2 Optimization of the reaction conditions for the
synthesis of 3-(4-methoxyphenylamino)-1-(4-methoxyphenyl)-
5-phenyl-1H-pyrrol-2(5H)-one (Scheme 2)
Entry
Catalyst
/mmol
T /°C Solvent (5 mL)
Yield /%a
1
2
1
1
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
n-Hexane
CH2Cl2
70
51
43
56
46
–
30
20
48
47
–
3
1
Et2O
4
1
EtOAc
5
1
EtOH
3-(p-tolylamino)-5-propyl-1-p-tolyl-1H-pyrrol-2(5H)-one (Table 3,
6
1
H2O
1
entry 9): M.p. 187–189 °C, H NMR (500 MHz, CDCl3): 1.27 (t,
7
1
H2O/EtOH (50/50%)
–
J = 7.2 Hz, 3H), 1.62–1.66 (m, 4H), 2.35 (s, 3H), 2.40 (s, 3H), 4.16–
4.27 (m, 1H), 5.94 (s, 1H), 6.61 (s, 1H), 7.01 (d, J = 8.4 Hz, 2H), 7.17
(d, J = 8.0 Hz, 2H), 7.24–7.28 (m, 4H); 13C NMR (125 MHz, CDCl3):
δ = 14.1, 20.7, 21.3, 62.1, 68.7, 106.8, 117.0, 125.7, 129.8, 129.9,
131.1, 133.3, 133.9, 136.9, 138.5, 167.6, 171.7 ppm; IR (KBr): 3308,
2984, 2956, 1694, 1648, 1612, 1592, 1539, 1515, 1447, 1393, 1311,
1270, 1247, 1176, 1110, 1030, 1009, 961, 915, 860, 814, 793 781,
758, 720 cm−1; Found: C, 78.75; H, 7.89; N, 8.85; C21H24N2O; requires:
C, 78.71; H, 7.55; N, 8.74%.
3-(4-methoxyphenylamino)-5-(4-tert-butylphenyl)-1-(4-methoxy-
phenyl)-1H-pyrrol-2(5H)-one (Table 3, entry 14): M.p. 249–251 °C,
1H NMR (400 MHz, CDCl3): 1.29 (s, 9H), 3.78 (s, 3H), 3.80 (s, 3H),
5.59 (d, J = 2.0 Hz, 1H), 5.95 (d, J = 2.4 Hz, 1H), 6.50 (s, 1H), 6.84–
6.89 (m, 4H), 7.06 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.31
(d, J = 8.0 Hz, 2H), 7.44 (d, J = 9.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3): δ = 31.3, 34.5, 55.4, 55.6, 64.3, 106.5, 114.1, 114.7, 118.4,
123.6, 125.8, 126.5, 130.5, 132.8, 134.5, 135.0, 151.0, 154.4, 156.8,
167.3 ppm; IR (KBr): 3319, 3055, 2962, 2834, 1668, 1650, 1593,
8
1
9
0.5
0.25
–
n-Hexane
n-Hexane
n-Hexane
10
11
a Isolated yields, reaction time: 120 min.
The work-up procedure is very simple. The products were
isolated and purified by simple filtration and washed with
diethyl ether. Our protocol has used ionic liquids in the
reaction process, making it superior to those reactions which
use hazardous liquid acidic catalysts.
In summary, an efficient protocol for the preparation of
1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-one
derivatives
has been described. The reactions were carried out at room
temperature with short reaction times and produce the

636 JOURNAL OF CHEMICAL RESEARCH 2011
Table 3 Synthesis of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-one derivatives using acidic ionic liquid as catalyst (Scheme 1)
Entry
Aldehyde
Amine
Time /min
Yield /%a
M.p. [lit m.p. °C]
1
2
Benzaldehyde
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methoxyaniline
4-Methylaniline
4-Methylaniline
4-Methylaniline
4-Methylaniline
4-Methylaniline
4-Chloroaniline
4-Chloroaniline
Cyclohexylamine
120
120
150
240
240
150
120
120
120
120
120
120
120
240
240
240
200
230
200
70
86
60
50
50
87
90
70
76
70
80
74
76
45
55
93
86
88
–
198–200 [197–199]9
143–145 [–]11
2,4-Dimethoxybenzaldehyde
2-Chlorobenzaldehyde
4-Nitrobenzaldehyde
3-Nitrobenzaldehyde
2-Methylbenzaldehyde
4-Methoxybenzaldehyde
4-Methylbenzaldehyde
4-tert-Butylbenzaldehyde
4-Chlorobenzaldehyde
3-Bromobenzaldehyde
Benzaldehyde
3
215–217 [–]11
4
214–216 [–]11
5
221–223 [–]11
6
195–198
7
153–155 [151–152]10
219–221 [218–220]9
249–251
8
9
10
11
12
13
14
15
16
17
18
19
191–196 [–]11
200–203 [–]11
215–217 [215–217]9
250–252 [249–251]9
143–145 [142–145]10
187–189
4-Methylbenzaldehyde
4-Nitrobenzaldehyde
Butyraldehyde
Furfural
Benzaldehyde
4-Chlorobenzaldehyde
4-Chlorobenzaldehyde
151–153 [151–152]10
216–218 [217–219]9
257–259 [258–260]9
–
a Isolated yields. All known products have been reported previously in the literature and were characterised by comparison of IR and
NMR spectra with authentic samples.9–11
2
3
4
5
R. Ballini, Eco-friendly synthesis of fine chemicals, Royal Society of
Chemistry, Science, Cambridge, 2009.
P. Wasserscheid, Ionic liquids in synthesis, Vol. 1, Wiley-VCH, Science,
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1541, 1514, 1463, 1442, 1428, 1406, 1364, 1300, 1253, 1180, 1114,
1031, 920, 870, 818, 776, 751, 736 cm−1; Found: C, 76.07; H, 6.91;
N, 6.39 C28H30N2O3; requires: C, 75.99; H, 6.83; N, 6.33%.
The authors are indebted to the Islamic Azad University –
Najafabad Branch for financial support of this research.
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7
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Received 23 September 2011; accepted 11 October 2011
Paper 1100902 doi: 10.3184/174751911X13191347034936
Published online: 22 November 2011
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