ZrCl4 as an efficient catalyst for one-pot four-component synthesis of polysubstituted dihydropyrrol-2-ones

Article abstract of DOI:10.1007/s11164-015-2178-z

An efficient synthesis of polysubstituted dihydropyrrol-2-one derivatives via one-pot four-component domino reaction of amines, dialkyl acetylenedicarboxylates and formaldehyde in the presence of zirconium tetrachloride (ZrCl₄) is described. The presented methodology offers several advantages such as simplicity of operation, good to high yields, short reaction times, inexpensive and readily available starting material and catalyst. Furthermore, the products were obtained through simple filtering with no need for column chromatography. Graphical abstract: [Figure not available: See fulltext.]

Full text of DOI:10.1007/s11164-015-2178-z

Res Chem Intermed
DOI 10.1007/s11164-015-2178-z
ZrCl4 as an efficient catalyst for one-pot four-
component synthesis of polysubstituted dihydropyrrol-
2-ones
Seyed Sajad Sajadikhah1 Malek Taher Maghsoodlou2
•
•
Nourallah Hazeri2 Sajad Mohamadian-Souri2
•
Received: 13 June 2015 / Accepted: 13 July 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract An efficient synthesis of polysubstituted dihydropyrrol-2-one derivatives
via one-pot four-component domino reaction of amines, dialkyl acetylenedicarboxylates
and formaldehyde in the presence of zirconium tetrachloride (ZrCl4) is described. The
presented methodology offers several advantages such as simplicity of operation, good
to high yields, short reaction times, inexpensive and readily available starting material
and catalyst. Furthermore, the products were obtained through simple filtering with no
need for column chromatography.
Graphical abstract
Keywords Heterocycle Á Dihydropyrrol-2-one Á ZrCl4 Á Dialkyl
acetylenedicarboxylate Á Multi-component reaction
Electronic supplementary material The online version of this article (doi:10.1007/s11164-015-2178-
z) contains supplementary material, which is available to authorized users.
&
Seyed Sajad Sajadikhah
sssajadi@pnu.ac.ir
1
2
Department of Chemistry, Payame Noor University (PNU), P. O. Box 19395-3697, Tehran, Iran
Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan,
P. O. Box 98135-674, Zahedan, Iran
123

S. S. Sajadikhah et al.
Introduction
Multi-component reactions (MCRs) play significant roles in organic chemistry as a
result of the fact that a final product can be formed by means of the reaction between
three or more different starting materials in a simple one-pot process [1]. In 1850,
Strecker reported the synthesis of a-aminonitrile by a three-component reaction of
ammonia, hydrocyanic acid and carbonyl compounds, which revealed the birth of
MCRs [2]. Since then, numerous MCRs have been invented and their number is still
growing. MCRs are advantageous compared to multistage syntheses due to their
traits such as flexibility, no separation of intermediates and simple purification of
products, atom-economy, time and energy savings, and environmental friendliness
by considerably reducing amounts of solvents and associated waste. Also, MCRs are
powerful tools in the modern drug discovery process and enable fast, automated,
and high-throughput generation of ‘drug-like’ molecules [3–5].
Among nitrogen-containing heterocycles, dihydropyrrol-2-ones display a broad
spectrum of biological and pharmacological activity as antitumor and anticancer
agents [6], an HIV integrase inhibitor [7], a DNA polymerase inhibitor [8], a human
cytomegalovirus (HCMV) protease inhibitor [9], and a human cytosolic carbonic
anhydrase isozymes inhibitor [10]. The dihydro-2-oxypyrrole moiety was also
found in various natural bioactive products, including pyrrocidine A, talaroconvo-
lutin A, thiomarinol A4 and oteromycin [11–13]. These heterocycles are also
important reagents as materials for the synthesis of organic complexes [14]. In view
of the importance of dihydropyrrol-2-one derivatives, several methods have been
developed to synthesize these useful heterocycles [15–20]. Recently, the literature
has presented some methods to synthesise polysubstituted dihydropyrrol-2-ones via
MCRs using catalysts such as acetic acid (AcOH), iodine (I2) , benzoic acid,
titanium dioxide (TiO2 ) nanopowder, Cu(OAc)2ÁH2O and (S)-camphorsulfonic acid
[21–27]. However, some of these methods displayed drawbacks, such as performing
the reaction in the presence of 200 mol% catalyst at 70 °C and purification of
products by preparative thin layer chromatography (TLC) [21], long reaction times
[23], environmental pollution caused by utilization of chlorinated solvent under
reflux conditions, and the need for column chromatography to purify the products
[24]. Therefore, it is necessary to further develop an efficient, milder and convenient
method to synthesis such important heterocycles.
During the past decade, the use of zirconium compound catalysts has received
considerable attention in organic chemistry as a catalyst because of their important
advantages, such as high catalytic activity, low toxicity, ease of handling and low
cost [28, 29].
As a part of our program aimed at developing a new procedure for the
preparation of dihydropyrrol-2-ones [30–35], in this work, we report an efficient and
very facile synthesis of polyfunctionalized dihydropyrrol-2-ones via one-pot four-
component reaction of amines, dialkyl acetylenedicarboxylates and formaldehyde in
the presence of a catalytic amount of zirconium tetrachloride (ZrCl4 ) in methanol at
ambient temperature (Scheme 1).
123

ZrCl4 as an efficient catalyst for one-pot four-component…
CO2R2
O
H
N
R1
ZrCl4 (25 mol%)
MeOH, rt
R1 NH2
Ar NH2
+
+
+
CH2O
N Ar
R2O2C
CO2R2
1
3
5
2
4
Scheme 1 Synthesis of polyfunctionalized dihydropyrrol-2-one 5
Results and discussion
In order to establish the optimized reaction conditions, the reaction between aniline,
dimethyl acetylenedicarboxylate (DMAD) and formaldehyde was chosen as a
model reaction and carried out in the presence of 10 mol% of various potential
catalysts, including ZrOCl2Á8H2O, ZrCl4, Zr(NO3)2, Bi(NO3)3Á5H2O, TiO2 and
Al2O3 at ambient temperature in methanol (Table 1). It was observed ZrCl4 is
superior, and produced the best yield of the desired product 5a. A control
experiment revealed that in the absence of the catalyst, only a trace amount of
product 5a was obtained.
Subsequently, a survey of solvents showed methanol to be the best choice. Low
yields were obtained when the model reaction was performed in ethanol, H2O,
acetonitrile, CH2Cl2 and CHCl3 (Table 2). To further optimize reaction conditions,
we investigated the effect of the loading amount of ZrCl4 on the model reaction in
methanol (Table 2, entries 6-11). The optimum yield of product 5a (84 %) was
obtained in the presence of 25 mol% of ZrCl4. By lowering the catalyst loading to
5 mol%, the corresponding product was obtained in lower yield (Table 2, entry 7),
while increasing the catalyst loading to 30 mol% has no significant effect on the
product yield (Table 2, entry 11).
Table 1 Effect of different catalysts on the reaction of aniline, DMAD and formaldehyde
CO2Me
CO2Me
NH2
NH2
O
H
N
Catalyst
+
+
CH2O
+
N
MeOH, rt
MeO2C
5a
Entry
Catalyst
Time (h)
Yield (%)a
1
2
3
4
5
6
7
ZrOCl2Á8H2O
ZrCl4
11
6
43
64
Zr(NO3)2
Bi(NO3)3Á5H2O
TiO2
8
40
8
37
8
39
Al2O3
8
26
None
12
Trace
Reaction conditions: Aniline (2 mmol), DMAD (1 mmol), formaldehyde (1.5 mmol), and catalyst
(10 mol%) in methanol (3 mL) at ambient temperature
a
Isolated yield
123

S. S. Sajadikhah et al.
Table 2 Investigation of
solvent effects and the amounts
of ZrCl4 on the model reaction
of Table 1
Entry Catalyst loading (mol%) Solvent Time (h) Yield (%)a
1
10
10
10
10
10
10
5
EtOH
H2O
10
16
52
10
41
20
23
64
47
73
80
84
85
2
3
MeCN 10
CH2Cl2 12
CHCl3 12
4
5
6
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
6
7
4
4
4
4
7
Reaction conditions: Aniline
(2 mmol), DMAD (1 mmol),
formaldehyde (1.5 mmol), and
ZrCl4 in 3 mL of solvent at
ambient temperature
8
15
20
25
30
9
10
11
a
Isolated yield
To further explore the scope and limitation of this protocol, a variety of
substituted anilines were reacted with dimethyl and/or diethyl acetylenedicarboxy-
late and formaldehyde under optimized conditions. The results are summarized in
Table 3. The reaction was found to be compatible with various functional groups
such as F, Cl, Br, Me and OMe. In all cases, the reaction proceeded smoothly to
produce the desired product in high yield (Table 3, entries 1–11). Next, two
different amines were employed for the synthesis of polysubstituted dihydropyrrol-
2-ones 5 m-y. Various aliphatic amines, including benzyl amine, 1-(pyridin-2-
yl)methanamine, n-propyl amine, n-buthyl amine and cyclohexyl amine, were used
in the reaction to afford the corresponding dihydropyrrol-2-one in good to high
yields (Table 3, entries 12-25). In general, at the beginning of the reaction, the
reagents were completely soluble in the reaction medium to form a homogeneous
mixture. But, at the end of the reaction, the product was precipitated and separated
by simple filtration. No column chromatography technique was used for product
purification, thereby avoiding use of large amounts of volatile organic solvents, as
the solvent is generally the main source of waste as well as environmental pollution.
Encouraged by these results, we improved the reaction scope by using ethane-
1,2-diamine as a reactant. The four-component (pseudo seven-component) reaction
of ethane-1,2-diamine, dialkyl acetylenedicarboxylates, aromatic amines and
formaldehyde (with mole ratio: 1:2:2:2) was carried out under optimal conditions
(Scheme 2). The corresponding bis-dihydropyrrol-2-ones 7a-j were obtained in
satisfactory yields (Table 4).
It is noted that the polysubstituted dihydropyrrol-2-ones can be obtained by
changing the sequence of amine addition (Scheme 3). For this aim, first a mixture of
aniline (1 mmol) and DMAD (1 mmol) in methanol (2 mL) was stirred for 20 min.
Next, a mixture of benzyl amine (1 mmol), formaldehyde and ZrCl4 (25 mol%) in
methanol (2 mL) was added dropwise. After completion of the reaction, the target
product 5z was obtained in moderate yield (67 %).
The structure of the products was characterized by their melting points and
infrared (IR) and nuclear magnetic resonance (NMR) spectral data, which were then
compared with those of authentic samples. As an unknown compound, the structure
123

ZrCl4 as an efficient catalyst for one-pot four-component…
Table 3 Synthesis of polysubstituted dihydropyrrol-2-ones 5a-y
Entry R1
R2
Ar
Product Time Yield Mp (lit. mp) [Ref.]a
(h)
(%)a
1
Ph
Me Ph
5a
5b
5c
5d
5e
5f
4
84
85
85
83
81
83
84
82
80
84
73
85
81
86
85
83
63
61
79
82
84
80
82
83
82
153–155 (155–156) [22]
164–166 (163–165) [30]
170–172 (173–174) [22]
180–182 (179–180) [22]
168–170 (168–170) [22]
133–135 (138–140) [21]
171–173 (172–173) [21]
168–170 (168–170) [32]
164–166 (169–171) [21]
128–130 (131–132) [21]
153–155 (152–154) [31]
138–140 (140–141) [21]
142–144 (147–148) [22]
118–120 (120–121) [22]
114–116 (New product)
144–146 (144–146) [33]
159–161 (159–161) [34]
106–108 (106–108) [32]
120–122 (124–125) [22]
103–105 (107–108) [21]
76–78 (78–79) [21]
2
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
Ph
Me 4-F-C6H4
Me 4-Cl-C6H4
Me 4-Br-C6H4
Me 4-Me-C6H4
3.5
4
3
4
3
5
4
6
Et
Et
Et
Et
Et
Et
Ph
3.5
4
7
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
4-OMe-C6H4
PhCH2
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
5g
5h
5i
8
3
9
4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
5j
4
4-OMe-C6H4 5k
6
Me Ph
5l
3.5
3
PhCH2
Me 4-Cl-C6H4
Me 4-Br-C6H4
5m
5n
5o
5p
5q
5r
5s
PhCH2
3.5
4
PhCH2
Et
4-Br-C6H4
PhCH2
Me 4-Me-C6H3
3
C5H4N-2-CH2 Me 4-Br-C6H4
C5H4N-2-CH2 Me 4-Me-C6H3
7.5
7
Cyclohexyl
Cyclohexyl
n-C3H7
Me 4-Cl-C6H4
3.5
3
Et
Et
Ph
Ph
5t
5u
5v
5w
5x
5y
4
n-C4H9
Me Ph
4
61–63 (60) [22]
n-C4H9
Me 4-F-C6H4
Me 4-Cl-C6H4
3.5
3
81–83 (81–83) [33]
n-C4H9
91–93 (92–94) [34]
n-C4H9
Et
4-Br-C6H4
4
94–96 (94–96) [30]
Isolated yield
a
Literature references for known compounds
CO2R2
CO2R2
O
H
Ar
N
ZrCl4 (25 mol%)
MeOH, rt
NH2
N
N
+
2
+
2 Ar NH2
+
2 CH2O
H2N
N
Ar
H
O
CO2R2
R2O2C
6
3
2
4
7
Scheme 2 Synthesis of substituted bis-dihydropyrrol-2-ones 7
1
of 5o also was fully characterized by IR, proton ( H) and carbon 13 ( 13C) NMR,
mass spectra as well as elemental analysis, and its structural assignment is described
below. The IR spectrum of 5o showed three absorption bands at 3307, 1698 and
1640 cm-1 due to the NH and carbonyl groups, respectively. The 1H NMR
spectrum of compound 5o exhibited a triplet and a quartet at 1.34 (J = 7.2 Hz) and
4.27 (J = 7.2 Hz) ppm for an ethoxy group. The methylene protons of
123

S. S. Sajadikhah et al.
M.p. (lit. m.p.)[Refs.]a
Table 4 Preparation of polysubstituted bis-dihydropyrrol-2-ones 7a-j
Entry
R2
Ar
Product
Time (h)
Yield (%)a
1
2
Me
Et
Ph
7a
7b
7c
7d
7e
7f
7
84
84
85
81
83
82
80
81
70
85
148–150 (149–151) [32]
210–212 (210–212) [32]
197–199 (199–201) [32]
206–208 (206–208) [32]
175–177 (174–176) [34]
207–209 (New product)
211–213 (New product)
159–161 (158–160) [35]
222–224 (219–221) [35]
202–204 (202–204) [35]
4-Me-C6H4
4-F-C6H4
3,4-Cl2-C6H3
4-Br-C6H4
4-Br-C6H4
4-Cl-C6H4
Ph
5.5
6
3
Me
Et
4
6
5
Et
5.5
7
6
Me
Et
7
7g
7h
7i
6
8
Et
8
9
Et
4-OMe-C6H4
4-Cl-C6H4
6
10
Me
7j
7
Isolated yield
a
Literature references for known compounds
O
H
NH2
NH2
CO2Me
N
ZrCl4 (25 mol%)
MeOH, rt, 7h
N
CH2O
+
+
+
MeO2C
CO2Me
5z
67%
Scheme 3 Synthesis of dihydropyrrol-2-one 5z by changing the sequence of amine addition
dihydropyrrol-2-one ring were observed as a singlet at 4.41 ppm. A doublet at
5.12 ppm (J = 6.4 Hz) appeared for methylene protons of a benzyl amine moiety.
The NH proton was exhibited as a broad singlet at d 6.90 ppm. The aromatic
protons were observed as two multiplets and two doublets at 7.28-7.33, 7.36-7.37,
7.52 (J = 8.8 Hz) and 7.70 (J = 8.8 Hz) ppm, respectively. The 13C NMR
spectrum of this compound showed 15 distinct resonances in agreement with the
suggested structure, and partial assignment of these resonances is given in the
experimental section. The mass spectrum of 5o displayed a molecular ion peak
(M?) at m/z = 414, and also peak M ? 2 at m/z = 416 due to the presence of a
bromine atom within this compound, which was consistent with the proposed
structure.
A possible reaction mechanism for the formation of dihydropyrrol-2-ones is
presented based on the reported literature [21, 22]. Firstly, the reaction of amine 1
(or 6) with dialkyl acetylenedicarboxylate 2 lead to intermediate 8. Secondly,
condensation between amine 3 and formaldehyde 4 in the presence of ZrCl4 produce
imine 9. Intermediate 8 possesses an enamine character and, thus, can readily react
with imine 9 to generate intermediate 10. Cyclization reaction of intermediate 10
lead to intermediate 11, that in the final step tautomerizes to the corresponding
mono- or bis-dihydro-2-oxopyrroles 5 or 7 (Scheme 4).
123

ZrCl4 as an efficient catalyst for one-pot four-component…
O
CO2R2
H
N
OR2
R1
ZrCl4
R1 NH2
+
+
O
R2O2C
CO2R2
N
1
OR2
R1
R2O2C
8
2
Cl4Zr
HN
ZrCl4
Ar
Ar NH2
CH2O
N
Ar
10
9
3
4
O
H
N
R1
N Ar
ZrCl4
R2O2C
O
N
R1
5
CO2R2
N Ar
H
O
H
Ar
N
R2O2C
N
R1 = CH2CH2NH2
N
H
N Ar
O
11
R2O2C
7
Scheme 4 Proposed mechanism for the formation of compounds 5 and 7
To show the efficiency and the applicability of the present work for the synthesis
of polysubstituted dihydropyrrol-2-ones, we compared results of ZrCl4 with
previously reported catalysts in the synthesis of compounds 5a, 5f (Table 5). The
results clearly show that ZrCl4 can act as an effective and efficient catalyst with
respect to yields and reaction times.
Experimental
General
The reagents and solvents used in this work were obtained from Merck (Darmastadt,
Germany), Acros (Geel, Belgium) and Fluka (Buchs, Switzerland), and were use
without further purification. Melting points and IR spectra were taken on an
Electrothermal 9100 apparatus and a JASCO FT/IR-460 plus spectrometer,
1
respectively. The H and 13C NMR spectra were recorded on a Bruker Avance
DRX-400 instrument with deuterated chloroform (CDCl3 ) as the solvent at 400 and
100 MHz, respectively. Elemental analyses for C, H and N were performed using a
Heraeus CHN-O-Rapid analyzer. The mass spectra were recorded on an Agilent
Technology (HP) mass spectrometer, operating at an ionization potential of 70 eV.
123

S. S. Sajadikhah et al.
Table 5 Comparison of ZrCl4 with reported catalysts for the synthesis of polysubstituted dihydropyrrol-
2-ones
Entry
1
Compound
Conditions
Time (h)
Yield (%)
Ref.
5a
I2 (10 mol%), MeOH, r.t.
1
6
82
91
[22]
[25]
Cu(OAc)2ÁH2O (0.4 mmol), benzaldehyde
(2 mmol, as additive), MeOH, r.t.
Al(H2PO4)3 (0.1 g), MeOH, r.t.
p-TsOHÁH2O (15 mol%), MeOH, r.t.
ZrCl4 (25 mol%), MeOH, r.t.
AcOH (2 mmol), EtOH, 70 °C
I2 (10 mol%), MeOH, r.t.
5
3
4
4
1
5
81
84
84
85
81
85
[31]
[34]
–
2
5f
[21]
[22]
[25]
Cu(OAc)2ÁH2O (0.4 mmol), benzaldehyde
(2 mmol, as additive), MeOH, r.t.
Al(H2PO4)3 (0.1 g), MeOH, r.t.
p-TsOHÁH2O (15 mol%), MeOH, r.t.
ZrCl4 (25 mol%), MeOH, r.t.
5
80
84
83
[31]
[34]
–
4
3.5
General procedure for the synthesis of polysubstituted dihydropyrrol-2-one 5 and
bis-dihydropyrrol-2-one 7 For product 5, a mixture of amine 1 (1 mmol) and
dialkyl acetylenedicarboxylate 2 (1 mmol) in methanol (3 mL) was stirred for
20 min. Then, aromatic amine 3 (1 mmol), formaldehyde 4 (37 % solution;
1.5 mmol) and ZrCl4 (25 mol%) were added successively. For compound 7, the
stoichiometric amounts of amine 6, dialkyl acetylenedicarboxylate 2, amine 3 and
formaldehyde 4 are 1, 2, 2 and 3 mmol, respectively. The reaction mixture was
stirred at ambient temperature for an appropriate time. After reaction completion
(monitored by TLC), the solid precipitate was filtered off and washed with ethanol
(3 9 2 mL) to afford the pure products 5 or 7. Physical and spectral data for the
new compounds are presented below.
Ethyl 3-(benzylamino)-1-(4-bromophenyl)-2,5-dihydro-2-oxo-1H-pyrrole-4-car-
boxylate (5o) White solid; mp: 114–116 °C; IR (KBr, cm-1): m 3307 (NH), 1698
1
(C = O), 1640 (C = O); H NMR (400 MHz, CDCl3): d 1.34 (t, J = 7.2 Hz, 3H,
OCH2CH3) 4.27 (q, J = 7.2 Hz, 2H, OCH2CH3), 4.41 (s, 2H, CH2–N), 5.12 (d,
J = 6.4 Hz, 2H, CH2–NH), 6.90 (br, 1H, NH), 7.28–7.33 (m, 1H, ArH), 7.36–7.37
(m, 4H, ArH), 7.52 (d, J = 8.8 Hz, 2H, ArH), 7.70 (d, J = 8.8 Hz, 2H, ArH); 13C
NMR (100 MHz, CDCl3): d 14.5, 46.6, 47.8, 60.0, 97.8, 117.7, 120.5, 127.4, 127.5,
128.7, 132.0, 137.8, 139.4, 164.5 (C = O), 165.1 (C = O); MS (EI, 70 eV): m/z (%)
416 (M ? 2, 21), 414 (M?, 21), 387 (31), 385 (29), 365 (25), 363 (23), 341 (15),
261 (17), 184 (6), 157 (5), 105 (10), 91 (100), 65 (15). Anal. Calcd. for
C20H19BrN2O3: C 57.84, H 4.61, N 6.75; Found: C 58.02, H 4.67, N 6.80.
Bis-(methyl 1-(4-bromophenyl)-3-(methyleneamino)-2,5-dihydro-2-oxo-1H-pyrrole-
4-carboxylate) (7f) Pale yellow solid; mp: 207–209 °C; IR (KBr, cm-1): m 3305
1
(NH), 1698 (C = O), 1637 (C = O); H NMR (400 MHz, CDCl3): d 3.68 (s, 6H,
2OCH3), 4.12–4.16 (m, 4H, 2CH2–NH), 4.26 (s, 4H, 2CH2–N), 6.77 (br s, 2H,
2NH), 7.48 (d, J = 8.8 Hz, 4H, ArH), 7.63 (d, J = 8.8 Hz, 4H, ArH); 13C NMR
123

ZrCl4 as an efficient catalyst for one-pot four-component…
(100 MHz, CDCl3): d 43.9, 47.7, 51.1, 117.8, 120.4, 132.0, 137.7, 164.4 (C = O),
165.0 (C = O); MS (EI, 70 eV): m/z (%) 648 (M?, 1), 368 (10), 236 (16), 152 (10),
111 (25), 97 (50), 83 (56), 69 (80), 57 (100); Anal. Calcd. for C26H24Br2N4O6: C
48.17, H 3.73, N 8.64; Found: C 48.50, H 3.91, N 8.55.
Bis-(ethyl 1-(4-chlorophenyl)-3-(methyleneamino)-2,5-dihydro-2-oxo-1H-pyrrole-
4-carboxylate) (7g) White solid, mp: 211-213 °C; IR (KBr, cm-1): m 3338 (NH),
1697 (C = O), 1641 (C = O); 1H NMR (400 MHz, CDCl3): d 1.28 (t, J = 6.8 Hz,
6H, 2OCH2CH3), 4.15 (br s, 8H, 2OCH2CH3 and 2CH2–NH), 4.31 (s, 4H, 2CH2–
N), 6.73 (br s, 2H, 2NH), 7.35 (d, J = 8.0 Hz, 4H, ArH), 7.71 (d, J = 8.4 Hz, 4H,
ArH); 13C NMR (100 MHz, CDCl3): d 14.4, 44.0, 47.9, 59.9, 98.5, 117.8, 120.2,
129.1, 130.0, 137.3, 164.5 (C = O), 165.3 (C = O); MS (EI, 70 eV): m/z (%) 588
(M ? 2, 5), 686 (M?, 8), 540 (6), 494 (8), 368 (6), 306 (100), 293 (33), 280 (15),
247 (70), 233 (51), 221 (45), 192 (14), 164 (12), 138 (30), 111 (25), 91 (34), 66 (44),
59 (27). Anal. Calcd. for C28H28Cl2N4O6: C 57.25, H 4.80, N 9.54; Found: C 57.54,
H 4.89, N 9.79.
Conclusion
In summary, we have described an efficient and simple strategy for the synthesis of
polysubstituted dihydropyrrol-2-ones and bis-dihydropyrrol-2-ones using ZrCl4 as a
catalyst in methanol at ambient temperature. The important aspects of this multi-
component heteroannulation are simple operations under mild conditions, good to
high yields, and readily available starting material and catalyst. Furthermore, all
products were obtained through simple filtration with no need for column
chromatography, which reduces the waste as well as environmental pollution.
Acknowledgments We gratefully acknowledge financial support from the research council of the
Payame Noor University (PNU) and the University of Sistan and Baluchestan.
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