Vitamin B12: An efficient type catalyst for the one-pot synthesis of 3,4,5-trisubstituted furan-2(5H)-ones and N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates

Article abstract of DOI:10.1016/j.cclet.2015.07.025

Vitamin B12 was applied as catalyst for the one-pot three-component synthesis of 3,4,5-trisubstituted furan-2(5H)-ones from the condensation between aldehydes, amines and dialkylacetylendicarboxylates at ambient temperature in EtOH. In addition, N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates were synthesised using mentioned catalyst at ambient temperature in EtOH from condensation between formaldehyde, amines, and dialkylacetylenedicarboxylates. This methodology has number of advantages such as: use of green and nonhazardous catalyst, clean work up, short reaction times, high yields and no need to column chromatography.

Full text of DOI:10.1016/j.cclet.2015.07.025

Accepted Manuscript
Title: Vitamin B12: An efficient type catalyst for the one-pot
synthesis of 3,4,5-trisubstituted furan-2(5H)-ones and
N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates
Author: Mehrnoosh Kangani Malek-Taher Maghsoodlou
Nourallah Hazeri
PII:
S1001-8417(15)00311-3
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.cclet.2015.07.025
CCLET 3402
To appear in:
Chinese Chemical Letters
Received date:
Revised date:
Accepted date:
12-6-2015
7-7-2015
13-7-2015
Please cite this article as: M. Kangani, M.-T. Maghsoodlou, N. Hazeri, Vitamin B12: An
efficient type catalyst for the one-pot synthesis of 3,4,5-trisubstituted furan-2(5H)-ones
and N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates, Chinese Chemical Letters
(2015), http://dx.doi.org/10.1016/j.cclet.2015.07.025
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Graphical Abstract
Vitamin B12: an efficient type catalyst for the one-pot synthesis of 3,4,5-trisubstituted furan-2(5H)-ones and N-aryl-3-
aminodihydropyrrol-2-one-4-carboxylates
Mehrnoosh Kangani, Malek-Taher Maghsoodlou*, Nourallah Hazeri
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, P.O. Box 98135-674, Zahedan, Iran
O
CO2R2
H
H
+
R1-NH
Ar-NH2
+
2
CO2R2
O
R1
NH
N-Ar
R2O2C
(product)
EtOH
room temprature
CO2R
CO2R
Catalyst
Ar1-NH2
Ar2-CHO
Ar1
HN
RO2C
Ar2
O
EtOH
room temprature
O
(product)
Vitamin B12 was applied as catalyst for the one-pot three-component synthesis of 3,4,5-trisubstituted furan-2(5H)-ones
from the condensation between aldehydes, amines and dialkylacetylendicarboxylates at ambient temperature in EtOH. In
addition, N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates were synthesis using mentioned catalyst at ambient
temperature in EtOH from condensation between formaldehyde, amines, and dialkylacetylenedicarboxylates.
Page 1 of 7

Original article
Vitamin B12: An efficient type catalyst for the one-pot synthesis of 3,4,5-trisubstituted
furan-2(5H)-ones and N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates
Mehrnoosh Kangani, Malek-Taher Maghsoodlou , Nourallah Hazeri
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, P.O. Box 98135-674,Zahedan, Iran
ARTICLE INFO
ABSTRACT
Vitamin B12 was applied as catalyst for the one-pot three-component synthesis of 3,4,5-
trisubstituted furan-2(5H)-ones from the condensation between aldehydes, amines and
dialkylacetylendicarboxylates at ambient temperature in EtOH. In addition, N-aryl-3-
aminodihydropyrrol-2-one-4-carboxylates were synthesis using mentioned catalyst at
ambient temperature in EtOH from condensation between formaldehyde, amines, and
dialkylacetylenedicarboxylates. This methodology has number of advantages such as: use
of green and nonhazardous catalyst, clean work up, short reaction times, high yields and no
need to column chromatography.
Article history:
Received 12 June 2015
Received in revised form 7 July 2015
Accepted 13 July 2013
Available online
Keywords:
Vitamin B12
3,4,5-Trisubstituted furan-2(5H)-ones
N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates
1. Introduction
Vitamin B12, also called cobalamin (Cbl), Cbl has been called nature’s most beautiful cofactor and was identified as the anti-
pernicious anemia factor from liver in 1948. Cbl shows biological activity in a very small amount. Cbl acts as the cofactor for two
enzymes, i.e., methylmalonyl-CoA mutase and methionine synthase, in humans. Both enzymes are important for health. The B 12
content in food is very low. Its greatest abundance is in meat, fish, and milk products; it is generally absent from fruits and vegetables,
but nor, an edible green and purple seaweed, is a non-dairy product that contains a significant amount of B12 Cbl found in food is
originally from these bacteria, in which the complex molecule is synthesized using at least 25 genes in the Cob operon. Cbl acts as the
cofactor for two enzymes present in humans [1] (Fig. 1). The properties and reactivity of vitamin B12 derivatives have been
extensively investigated ever since it was shown to possess a cobalt-carbon bond in the biological cofactors adenosyl and
methylcobalamin [2-6]. These versatile organometallic complexes are used in a variety of enzymes to catalyze radical rearrangements
and methyltransfers. Moreover, vitamin B12 has found use in organic chemistry for carbon-carbon bond formations [7-12].
Furanones are the five-member heterocyclic compounds possessing lactone ring in their structures. These heterocycles are the core
structures of many bioactive natural products as well as synthetic drugs such as rubrolide, sarcophine, benfurodilhemisuccinate, etc.
[13, 14]. 5H-Furan-2-onederivatives exhibit many pharmacological and biological activities including antifungal, antibacterial, anti-
oxidants, anti-inflammatory, anti-microbial and anti-cancer agents [15–19]. Due to this wide range of abundance and applicability,
various approaches toward substituted butenolides have been developed, which involve the use of organo-lithium [20], boronic acids
[21,22], transition-metal catalysts such as Pd(OAc)2 [23], Ru [24], Cu(II) [25], AuCl [26], and secondary amines [27]. However, many
of these methods involve the use of expensive catalysts and hazardous reagents in stoichiometric amounts. A new route to the synthesis
of furan skeletons was developed by Murthy et al. via the multi-component reaction of aromatic amines, aldehydes and acetylenic
esters, which lead to the preparation of 3,4,5-substituted furan-2(5H)-one derivatives using β-cyclodextrin as a catalyst in water [28].
Recently, Nagarapu et al. reported that SnCl2 can efficiently catalyze this reaction [29]. The presence of pyrrol-2-ones (5-lactams or g-
lactams) in pharmaceuticals and natural products has continued to stimulate a great deal of interest in the development of new
methodologies for their synthesis [30,31]. There are several bioactive natural molecules with a pyrrol-2-one moiety, such as holomycin
and thiolutin [32], thiomarinol A4 [33], oteromycin [34], pyrrocidine A [35], quinolactacin C [36], and ypaoamide [37]. On the other
hand, dihydropyrrol-2-ones have been successfully used as peptidomimetic [38], HIV integrase [39], herbicidals [40], DNA
polymerase inhibitors [41], caspase-3 inhibitors [42] cytotoxic and antitumor agents [43], antibiotics [44], and also inhibitors of the
annexin A2-S100A10 protein interaction [45]. Recently, a few methods have been reported for the synthesis of highly substituted
dihydropyrrol-2-ones using one-pot, four-component reactions in the presence of catalyst, such as AcOH, I2, benzoic acid, TiO2
_
nanopowder or Cu(OAc)2 H2O [46–51]. However, some of these methods have drawbacks, such as high temperature and utilize a
———
Corresponding author.
E-mail address: mt_maghsoodlou@yahoo.com, mt_maghsoodlou@chem.usb.ac.ir
Page 2 of 7

chlorinated solvent. Therefore, the development of a milder and more efficient route for one-pot synthesis of these important
heterocycles is still in demand. Thus, in continue of our research on multi-component synthesis [52-55],we herein report a green
synthesis of 3,4,5-trisubstituted furan-2(5H)-ones and N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates using catalytic amount of
vitamin B12 as catalyst at ambient temperature in EtOH (Schemes 1 & 2).
Fig 1. The structure of vitamin B12.
2. Experimental
2.1. Chemistry
Chemicals were purchased from Merck (Darmastadt,Germany), Acros (Geel, Belgium) and Fluka (Buchs, Switzerland), and used
without further purification. The Vitamin B12 was purchased from the Sigma-Aldrich company. Melting points were taken on an
1
Electrothermal 9100 apparatus. IR spectra were obtained on a JASCO FT/IR-460 plus spectrometer. The H NMR and 13C NMR
spectra were recorded on a Bruker DRX-400 Avanve instrument with CDCl3 as solvent and using TMS as internal reference at 400
MHz and 100 MHz, respectively.
2.2 General procedure for the synthesis of 3,4,5-trisubstituted furan-2(5H)-ones
A mixture of amine 1 (1 mmol), dialkylacetylenedicarboxylate 2 (1 mmol), aromatic aldehyde 3 (1mmol) and vitamin B12 (0.001g)
in EtOH (2 mL) was stirred at ambient temperature for appropriate time (Scheme 1). After completion of the reaction (monitored by
TLC), the water was added to produce solid precipitate, and the precipitate was filtered off and washed with ethanol (3×2 mL) to give
1
the pure product 4. The structures of the synthesized compounds were characterized by their IR, H NMR and 13C NMR spectra and
were found to be identical with data described in the literature.
Ar1
CO2R
HN
RO2C
cat. B12
Ar1-NH2
Ar2-CHO
O
+
+
EtOH (2 mL), r.t.
O
Ar2
CO2R
1
3
2
4a-o
Scheme 1. Synthesis of 3,4,5-trisubstituted furan-2(5H)-ones in the presence of vitamin B12 as catalyst in EtOH at ambient temperature.
2.3 General procedure for the synthesis of N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates
A mixture of amin 5 (1 mmol) and dialkylacetylenedicarboxylate 6 (1 mmol) in EtOH (2 mL) was stirred for 25 min. Next, amine 7
(1 mmol), formaldehyde 8 (37% solution, 1.5 mmol) and vitamin B12 (0.001 g) were added in successively. The reaction mixture was
allowed to stir at ambient temperature for appropriate time. After completion of the reaction (monitored by TLC), the water was added
to produce solid precipitate, and the precipitate was filtered off and washed with ethanol (3× 2 mL) to give the pure product 9 (Scheme
1
2). The structures of the synthesized compounds were characterized by their IR, H NMR and 13C NMR spectra and were found to be
identical with data described in the literature [47,48].
O
CO2R2
R1
R1-NH2
NH
O
5
cat. B12
+
+
N-Ar
H
H
EtOH (2 mL), r.t.
Ar-NH2
R2O2C
8
CO2R2
7
6
9a-p
Page 3 of 7

Scheme 2. Synthesis of N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates in the presence of vitamin B12 as catalyst in EtOH at ambient temperature.
Methyl 2,5-dihydro-5-oxo-2-phenyl-4-(phenylamino)furan-3-carboxylate (4a): White solid; IR (KBr, cm-1): 3260, 3208, 1702, 1661;
1H NMR (400 MHz, CDCl3): δ 3.77 (s, 3 H, OCH3), 5.76 (s, 1H, benzylic), 7.13 (t, 1H, J = 7.3 Hz),7.24–7.31 (m, 7H), 7.52 (d, 2H, J =
8 Hz), 8.90 (br, NH, 1H); 13C NMR (100 MHz, CDCl3): δ 165.3 and 162.7 (CO), 156.3, 136.1, 134.9,129.0, 128.7, 128.6, 127.4, 125.9,
122.3, 112.8 (C of aromatic), 61.6(C of methoxy), 52.1 (C of benzylic).
Methyl 4-(p-tolylamino)-2,5-dihydro-5-oxo-2-phenylfuran-3-carboxylate (4b): White solid; IR (KBr, cm-1): 3228, 2950, 1706, 1677,
1513; 1H NMR (400 MHz, CDCl3): δ 2.27 (s, 3H, CH3), 3.76 (s, 3H, OCH3), 5.72 (s, 1H, benzylic),7.09 (d, 2H, J = 8 Hz), 7.22–7.270
(m, 5H, aromatic), 7.34 (d, 2H, J = 8.4 Hz), 8.86 (br, 1H, NH); 13C NMR (100 MHz, CDCl3): δ 165.3 and 162.8 (CO), 156.4, 135.8,
135.0, 133.5, 129.6, 128.6,128.5, 127.5, 122.4, 112.6 (C of aromatic), 61.3 (C of methoxy), 52.0 (C of benzylic), 20.9 (C of methyl).
Ethyl 2-(4-cyanophenyl)-2,5-dihydro-5-oxo-4-(phenylamino)-furan-3-carboxylate (4e): White solid; IR (KBr, cm-1): 3293 (NH),
2977, 2225 (CN), 1731, 1684,1666, 1500; 1H NMR (400 MHz, CDCl3): δ 1.23 (t, 3H, J = 7.2 Hz,CH3), 4.24 (q, 2H, J = 7.2 Hz, CH2),
5.82 (s, 1H, benzylic), 7.17 (t, 1H, J = 7.2 Hz), 7.32–7.47 (m, 6H, aromatic), 7.59 (d, 2H, J = 8 Hz), 9.03 (br, 1H, NH); 13C NMR (100
MHz, CDCl3): δ 164.6 and 162.5 (CO), 156.89, 140.8, 135.7, 132.5, 129.2, 128.3, 126.3, 122.1, 118.1,112.6 (C of aromatic), 112.2 (C
of CN), 61.6 (C of methoxy), 60.8 (C of benzylic),14.0 (C of ethoxy).
Methyl 2,5-dihydro-5-oxo-1-phenyl-4-(phenylamino)-1H-pyrrole-3-carboxylate (9a): White solid, IR (KBr, cm-1): 3310 (NH), 1705,
1
1684, 1645; H NMR (400 MHz, CDCl3): δ 3.76 (s, 3H, OCH3), 4.57 (s, 2H, CH2), 7.16-7.23 (m, 4H, ArH),7.34 (t, 2H, J = 8.0 Hz,
ArH), 7.42 (t, 2H, J = 8.0 Hz, ArH), 7.81 (d, 2H, J = 8.0 Hz, ArH), 8.05 (br s,1H, NH).
Ethyl 4-(p-tolylamino)-2,5-dihydro-5-oxo-1-p-tolyl-1H-pyrrole-3-carboxylate (9d): Yellow solid, IR (KBr, cm-1): 3310 (NH), 1707,
1
1682, 1649; H NMR (400 MHz, CDCl3): δ 1.25 (t, 3H, J = 7.2 Hz, OCH2CH3), 2.36 (s, 3H, CH3), 2.37 (s, 3H, CH3),4.23 (t, 2H, J =
7.2 Hz, OCH2CH3), 4.52 (s, 2H, CH2), 7.06 (d, 2H, J = 8.4 Hz, ArH), 7.14 (d, 2H, J = 8.0 Hz, ArH), 7.21 (d, 2H, J =8.4 Hz, ArH), 7.69
(d, 2H, J = 8.8 Hz, ArH), 8.01 (br s, 1H, NH);13C NMR (100 MHz, CDCl3): δ 164.7 and163.7 (CO), 143.1,136.3, 136.2, 134.6, 134.2,
129.6, 128.9, 122.9, 119.1, 102.4(C of aromatic), 48.3 (CH2-N), 60.2 (C of methoxy), 21.0 (Cof methyl), 20.9 (C of methyl), 14.2 (C of
ethoxy).
Methyl 4-(benzylamino)-1-p-tolyl-2,5-dihydro-5-oxo-1H-pyrrole-3-carboxylate (9m): White solid, IR (KBr, cm-1): 3310 (NH), 1704,
1682, 1646; 1H NMR (400 MHz, CDCl3): δ 1.34 (t, 3H, J = 7.2 Hz, OCH2CH3), 4.27 (t, 2H, J = 7.2 Hz, OCH2CH3), 4.41 (s, 2H, CH2-
N), 5.12 (d, 2H, J = 6.4 Hz, CH2-NH), 6.90 (br s, 1H, NH), 7.28-7.37 (m, 5H, ArH), 7.52 (d, 2H, J = 8.8 Hz, ArH), 7.70 (d, 2H, J = 8.8
Hz, ArH); 13C NMR (100 MHz, CDCl3): δ 165.6 and 164.3 (CO), 139.5, 136.2, 134.8, 129.6, 128.7, 127.5, 127.3, 119.4, 97.1(C of
aromatic),51.0 (C of methoxy), 48.0 and 46.6 (CH2-N), 20.9 (C of methyl).
3. Results and discussion
The reaction condition was optimized for the synthesis of 3,4,5-substituted furan-2(5H)-one derivatives, for this purpose the
reaction between benzaldehyde, aniline and dimethylacetylendicarboxylate was chosen as a model system. The reaction was initially
carried out in different conditions (Table 1). Since we wanted to present a green and environmentally benign protocol for this
experiment, we did not test organic solvents under these conditions.
Table 1
Optimization of the reaction conditions for the synthesis of 4a in EtOH.a
Entry
Catalyst (mo l %)
Time (h)
Isolated
yields (%)
1
2
3
4
5
6
7
8
TiO2 (10)
Zn(SO4)2-7H2O (10)
Zr(NO3)4 (10)
ZrCl4 (10)
HClO4–SiO2 (10)
KHSO4 (10)
10
9
9
9
9
9
9
2
25
25
30
50
20
26
40
85
NH4HSO4 (10)
Vitamin B12 (7.35 * 10-5)
a Amounts of material in all reactions: aldehyde (1 mmol), aniline (1 mmol) and DMAD (1 mmol).
The scope and efficiency of these procedures were explored for the synthesis of a wide variety of substituted 3,4,5-substituted
furan-2(5H)-ones (Table 2). Generally, the results were excellent in terms of yield and product purity. A series of aromatic aldehydes
and amines were investigated (Table 2, products 4a–o). In all cases, aromatic aldehydes containing electron-donating groups gave
shorter times and higher yields than that with electron-withdrawing groups.
Table 2
Synthesis of 3,4,5-substituted furan- 2(5H)-ones.
Product
Ar 1
Ar2
R
Time (min)
120
Isolated
yield (%)
85
mp (°C)
159-162
Lit.mp (°C) [Ref]
159-162 [24]
4a
Ph
Ph
Me
Page 4 of 7

4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
Ph
4-Me–C6H4
Ph
Ph
Ph
4-F-C6H4
4-Cl-C6H4
3-NO2-C6H4
Ph
Me
Me
Me
Et
Me
Me
Me
Me
Me
Et
60
60
60
120
60
60
90
60
80
60
60
60
60
60
75
85
75
80
85
85
80
85
80
90
90
85
80
80
280-282
179-180
148–150
152–154
290-293
167–170
199-202
235-238
129-130
166–168
119–121
185-186
180-182
174-176
284-287 [24]
181-183 [24]
149-152 [24]
152–154 [52]
293-295 [25]
165–166 [53]
203-205 [53]
239-242 [53]
130-131[53]
164–166 [22]
120–121 [22]
188-191 [22]
184-185 [22]
174 [22]
4-Me-C6H4
4-Cl-C6H4
4-CN-C6H4
Ph
Ph
Ph
4-OMe–C6H4
4-NO2–C6H4
Ph
Ph
Ph
Ph
4-Me–C6H4
Et
Et
Et
Et
4-Me–C6H4
4-Cl–C6H4
4-OMe–C6H4
Ph
Ph
Ph
A proposed mechanism for the formation of 4 is shown in Scheme 3. There are many reactive sites in the vitamin B12 molecule that
can active carbonyl group (Fig.1).
O
H
N
OR2
Ar1
O
Ar1
CO2R2
HN
H
O
Ar1
R2O2C
OR2
O
N
Ar1
N
H
RO2C
Ar2
O
Ar1-NH2
+
O
a
R2O2C
O
CO2R2
Ar2
H
Ar2
R2O2C
H
O
H
c
2
1
C
O
b
H2N
4
Ar2
Co
H2N
3
Scheme 3. Proposed mechanism for the one-pot three-component synthesis of 3,4,5-substituted furan-2(5H)-ones in the presence of vitamin
B12 as green catalyst.
Next, the reaction condition was optimized for the synthesis of N-aryl-3aminodihydropyrrol-2-one-4-carboxylates. Formaldehyde,
aniline, and dimethylacetylenedicarboxylate were chosen as model compounds. The reaction was initially carried out in different
condition (Table 3). As can be seen in Table 3, catalytic amount of vitamin B12 (7.35 * 10-5 mol%) was found to be the most effective
catalyst for the reaction at room temperature.
Table 3
Optimization of the reaction conditions for the synthesis of 9a in EtOH.a
Entry
Catalyst (mol%)
Time (h)
Isolated yields
(%)
25
25
30
50
20
26
40
75
1
2
3
4
5
6
7
8
TiO2 (10)
Zn(SO4)2-7H2O (10)
Zr(NO3)4 (10)
ZrCl4 (10)
HClO4–SiO2 (10)
KHSO4 (10)
15
15
12
12
12
15
15
2
NH4HSO4 (10)
Vitamin B12 (7.35 * 10-5)
a Amounts of material in all reactions: aniline (2 mmol), DMAD (1 mmol), and formaldehyde (1.5 mmol).
To demonstrate the utility and generality of this method, the various substituted anilines, dimethyl or diethyl acetylenedicarboxylates
and formaldehyde were employed successfully to generate the desired N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates 9a–h (Table
4). Encouraged by these results, different polyfunctionalized dihydropyrrol-2-ones 9i–p were synthesized using two different amines.
Aliphatic amines, such as benzyl amine, 1-(pyridin-2-yl)methanamine and n-butyl amine, were reacted with dialkylacetylene-
dicarboxylates, anilines and formaldehyde to produce the corresponding products in good to high yields.
Table 4
Synthesis of N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates.
Product
9a
9b
9c
9d
9e
9f
9g
R1
Ph
Ph
R2
Me
Et
Me
Et
Et
Me
Et
Ar
Ph
Ph
Time (min)
120
60
90
60
120
60
60
Isolated yield (%)
m.p (°C)
154–155
136–138
177–179
128–130
152–154
163–165
167–170
167–169
Lit.mp (°C) [Ref]
155–156 [48]
138–140 [47]
177–178 [48]
131–132 [47]
152–154 [54]
163–165 [53]
168–170 [53]
169–171 [53]
75
85
85
85
80
85
85
80
4-Me-C6H4
4-Me-C6H4
4-OMe-C6H4
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
4-Me-C6H4
4-OMe-C6H4
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
9h
Et
90
Page 5 of 7

9i
9j
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
C5H4N-2-CH2
n-C4H9
Me
Et
Ph
Ph
60
60
60
60
60
60
60
60
85
80
90
90
85
80
80
85
136–138
81 127
140–141 [47]
129 130 [47]
166–168 [53]
120–121 [48]
144–146 [53]
106–108 [47]
60 [48]
9k
9l
9m
9n
9o
9p
Me
Me
Me
Me
Me
Et
4-F-C6H4
4-Br-C6H4
4-Me-C6H4
4-Me-C6H4
Ph
166–168
119–121
144–146
104–106
60–62
n-C4H9
4-Br-C6H4
94–97
94–96 [53]
On the basis of the above experimental results, together with the related reports, a proposed reaction mechanism for this one-pot,
four-component hetero-annulations is illustrated in Scheme 4.
O
CO2R2
H
OR2
N
R1
R1-NH2
+
O
O
R2O2C
O
R1
H
R1
CO2R2
a
NH
OR2
N
N
H
R1
N-Ar
5
N-Ar
6
R2O2C
R2O2C
R2O2C
O
NH
H
O
Ar-NH2
+
Ar
NH
9
H
H
Ar
7
H2N
H2N
d
c
8
Co
b
Scheme 4. Proposed mechanism for the one-pot four-commponent synthesis of N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates in the
presence of vitamin B12 as catalyst.
4. Conclusion
In summary, we report an eco-friendly and straightforward one-pot condensation for the synthesis of 3,4,5-trisubstituted furan-
2(5H)-ones and N-aryl-3-aminodihydropyrrol-2-one-4-carboxylates in the presence of catalytic amount of vitamin B12 as a highly
effective ,green and homogenous catalyst. Vitamin B12 is clean, safe, non-toxic, and easy access. Moreover, this method has several
other advantages such as, high yields, operational simplicity, clean and neutral reaction conditions, which makes it a useful and
attractive process for the synthesis of a wide variety of biologically active compounds.
Acknowledgment
We gratefully acknowledge financial support from the Research Council of the University of Sistan and Baluchestan.
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