Microwave domino diastereoselective synthesis of novel trans-4,5-dihydro-1H-furo[2,3-c]pyrazoles using pyridinium salts in an aqueous medium

Article abstract of DOI:10.3184/174751918X15241613654928

Novel fused 4,5-dihydro-1H-furo[2,3-c]pyrazole derivatives containing both biologically active pyrazole and furan templates are synthesised by a one-pot two-step four-component domino reaction involving hydrazine hydrate, a β-keto ester, an aromatic aldehyde and a pyridinium salt catalysed by DABCO with high diastereoselectivity in H₂O under microwave irradiation. To minimise the formation of byproducts, the hydrazine hydrate and ethyl acetoacetate were first irradiated until a pyrazolone was formed. Next, the aryl aldehyde, the pyridinium salt and DABCO were added and the reaction could be completed in good to excellent yields. The salient features of this eco-friendly methodology are highlighted by its short reaction time (10–12 min), high yields, high atom-economy, efficiency of producing five new bonds (2C–C, C=N, C–N and one C–O), two new rings and two stereocentres in a single operation, absence of any tedious work-up or purification and avoidance of separation of intermediates.

Full text of DOI:10.3184/174751918X15241613654928

JOURNAL OF CHEMICAL RESEARCH 2018
VOL. 42 APRIL, 219–223
RESEARCH PAPER 219
Microwave domino diastereoselective synthesis of novel trans-4,5-dihydro-1H-
furo[2,3-c]pyrazoles using pyridinium salts in an aqueous medium
a
a
b
c
Afshin Yazdani-Elah-Abadi *, Reza Morekian , Nasim Simin and Mojtaba Lashkari
a
Department of Food Industry Engineering, Science and Art University, Yazd, Iran
Young Researchers and Elite Club, Tuyserkan Branch, Islamic Azad University, Tuyserkan, Iran
Faculty of Science, Velayat University, Iranshahr, Iran
b
c
Novel fused 4,5-dihydro-1H-furo[2,3-c]pyrazole derivatives containing both biologically active pyrazole and furan templates are
synthesised by a one-pot two-step four-component domino reaction involving hydrazine hydrate, a β-keto ester, an aromatic aldehyde
and a pyridinium salt catalysed by DABCO with high diastereoselectivity in H O under microwave irradiation. To minimise the formation of
2
byproducts, the hydrazine hydrate and ethyl acetoacetate were first irradiated until a pyrazolone was formed. Next, the aryl aldehyde, the
pyridinium salt and DABCO were added and the reaction could be completed in good to excellent yields. The salient features of this eco-
friendly methodology are highlighted by its short reaction time (10–12 min), high yields, high atom-economy, efficiency of producing five
new bonds (2C–C, C=N, C–N and one C–O), two new rings and two stereocentres in a single operation, absence of any tedious work-up or
purification and avoidance of separation of intermediates.
Keywords: dihydro-1H-furo[2,3-c]pyrazole, pyridinium salt, multi-component domino reactions, microwave-assisted reaction, green chemistry
In recent years, green chemistry techniques have attracted
considerable attention in the chemical industry and research
laboratories due to environmental, health and economic
benefits. The proper choice of starting materials (use of safe,
readily available, cheap and environmentally benign reagents),
atom economic methodologies with a minimum number
of chemical steps, the appropriate use of multicomponent
reactions, microwave irradiation, water as solvent medium,
PEG-400, reusable heterogeneous catalytic conditions, solvent-
free conditions, ionic liquids and efficient strategies for product
isolation and purification are part of the movement towards
increasingly important to the pharmaceutical, chemical and
14–16
agricultural industries in recent years.
These five-membered
heterocycles are a key class of bioactive heterocycles and may
possess antimicrobial, anticancer, analgesic, antiinflammatory,
anti-tubercular, antidepressant, antihelmintic, anticonvulsant,
17,18
antipyretic, antioxidant or herbicidal properties.
Furan-based compounds are a large group of O-containing
heterocycles that are obtained from both synthetic and
natural sources and have attracted great attention due to their
1
9–21
wideranging pharmaceutical applications.
furopyrazole based molecules are anti-leukaemia agents
and derivatives have shown antimicrobial and antitumour
Among them,
2
2
1–5
green chemistry for reaction sustainability. In this context,
microwave-assisted organic synthesis (MAOS) has developed
into an important branch of synthetic organic chemistry for
the synthesis of complex heterocyclic molecules. MAOS is a
powerful technique that is used to accelerate organic reactions
and significant advantages of the microwave approach are
shorter reaction times, enhancements in yields and easier
2
3
activities. However, access to dihydrofuro[2,3-c]pyrazoles of
2
4–27
the type 6 (Scheme 1) is limited.
Results and discussion
Motivated by the above and in continuation of our research in
the synthesis of complex organic compounds utilising green
6
,7
28–31
manipulation.
chemistry,
we report here our results for the efficient domino
Consequently, the design of novel multicomponent domino
reactions using microwave irradiation for the synthesis of simple
and complex bioactive heterocycles has become a notable topic
synthesis of novel highly substituted furanopyrazole derivatives
6a–j by a one-pot two-step four-component condensation
reaction between hydrazine hydrate (1), a β-ketoester 2, a
benzaldehyde 4 and a pyridinium salt 5 catalysed by DABCO
as a highly reactive, inexpensive, non-toxic and easy to handle
catalyst under microwave irradiation (MW) (180 W, max.
70 °C) in an aqueous medium (Scheme 1).
In order to investigate optimal reaction conditions for the
synthesis of the furanopyrazoles, we carried out the two-step
four-component domino reaction between hydrazine hydrate
(1) (1.2 mmol) (see SAFETY CAUTION in Experimental),
8
,9
in the drug discovery process and analysis of drugs. Among
them, functionalised nitrogen- and oxygen-heterocycles are
10
widespread in medicinal agents and natural products and
these compounds are of interest due to their applications
as biologically active agrochemicals, pharmaceuticals and
11–13
functional materials.
Pyrazoles and derivatives are a major category of nitrogen-
containing heterocyclic compounds that have become
Scheme 1 DABCO-catalysed domino synthesis of novel 4,5-dihydro-1H-furo[2,3-c]pyrazole derivatives 6a–j under microwave irradiation in H O.
2
*
Correspondent. E-mail: afi_yazdani@yahoo.com

220 JOURNAL OF CHEMICAL RESEARCH 2018
ethyl acetoacetate (2) (1.0 mmol), 4-nitrobenzaldehyde (4)
1.0 mmol) and N-phenacylpyridinium bromide 5 (1.0 mmol)
of the dihydrofuran ring displayed two doublets at δ 5.11 and
6.02 ppm with the vicinal coupling constant J = 4.5 Hz. It
has been documented that in cis-2,3-dihydrofuran the vicinal
coupling constant of the two methine protons is J = 7–10 Hz,
while in trans-2,3-dihydrofuran the vicinal coupling constant
(
as a model reaction. To minimise the formation of byproducts,
hydrazine hydrate and ethyl acetoacetate were irradiated in a
microwave oven at 180 W in water until, in less than 3 min,
a white solid of pyrazolone (3) was formed without using any
catalyst. Next, 4-nitrobenzaldehyde and N-phenacylpyridinium
bromide were added and the mixture was irradiated at the same
temperature (180 W, max. 70 °C). The desired product 6a was
not obtained when the reaction was carried out under catalyst-
free conditions for 20 min (Table 1, entry 1). However, 6a was
obtained in 82% yield when the reaction was conducted in the
32–34
is J = 4–7 Hz.
We conclude that the theromodynamically
stable trans isomer of the 2,3-dihydrofuran derivative with
13
high diastereoselectivity was formed. The C NMR spectrum
of 6a showed 17 distinct resonances probably due to restricted
rotation. Similarly, compounds 6b–j were characterised
(Table 2).
A mechanism for the formation of 6 is proposed in Scheme
2. The reaction proceeds by initial condensation of hydrazine
hydrate (1) and ethyl acetoacetate (2) to generate pyrazolone
(3), which isomerises to intermediate 7. DABCO is an efficient
catalyst to form the olefin 8 by Knoevenagel condensation
of aromatic aldehyde 4 with pyrazole (7). Subsequently
Michael addition of the pyridinium salt 9, which is formed
by deprotonation of the 1-[2-aryl-2-oxoethyl]pyridinium 5 by
DABCO, to intermediate 8 affords the zwitterionic salt 10.
Finally, the enolate 10 eliminates a pyridyl group and cyclises to
give the fused 4,5-dihydro-1H-furo[2,3-c]pyrazole derivative 6.
presence of Et N (20 mol%) as catalyst (Table 1, entry 2). In
3
order to identify effective reaction conditions the reaction was
optimised in terms of catalyst, catalyst loading and influence of
microwave irradiation and the results are summarised in Table
1. We found that the optimised yields and time profiles were
obtained when the reaction was carried out in the presence of
2
7
4
0 mol% DABCO under microwave irradiation at 180 W (max.
0 °C) in H O, which afforded the corresponding [3-methyl-
2
-(4-nitrophenyl)-4,5-dihydro-1H-furo[2,3-c]pyrazol-5-yl]
(phenyl)methanone (6a) in 10 min in 87% yield (Table 1, entry
6
). Increasing the amount of DABCO to 30 mol% showed no
Conclusions
substantial improvement in the yield and the yield decreased on
reducing the amount of DABCO to 10 mol%.
We have introduced an environmentally benign approach for
the facile and efficient synthesis of novel 4,5-dihydro-1H-
furo[2,3-c]pyrazoles in high yields by a one-pot two-step four-
component domino protocol using DABCO as a mild, effective,
non-toxic and inexpensive solid base catalyst and involving
To generate a small library of functionalised 4,5-dihydro-
H-furo[2,3-c]pyrazole derivatives, we tested a variety of
pyridinium salts and different aromatic aldehydes including
electron-withdrawing and electron-donating groups to explore
the synthetic scope and versatility of this reaction under the
optimised conditions.
1
Knoevenagel
condensation/Michael
addition/cyclisation
sequences under microwave irradiation in an aqueous medium.
The promising points for the methodology are environmental
acceptability, excellent chemoselectivity, economic viability,
easy work-up, short reaction time, high atom-economy and
finally compliance with green chemistry protocols. Moreover,
our products are expected to be of pharmacological interest and
The isolated products 6 were fully characterised on the
1
13
basis of IR, H and C NMR and elemental analysis. In the
–1
IR spectrum, a stretching frequency at 1691 cm confirmed
the presence of the C=O functional group of compound 6a.
1
In the H NMR spectrum, the two protons at the 2,3-position
a
Table 1 Optimisation of reaction conditions for the synthesis of compound 6a
c
d
Entry
Catalyst
No catalyst
Reaction conditions
H2O, 180 W
H2O, 180 W
H2O, 180 W
H2O, 180 W
H2O, 180 W
H2O, 180 W
H2O, 300 W
H2O, 100 W
H2O, 180 W
H2O, 180 W
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
20
10
10
10
10
10
7
15
10
10
No reaction
Et N (20 mol%)
82
67
75
53
87
83
71
85
78
3
Piperidine (20 mol%)
DBU (20 mol%)
K CO (20 mol%)
2
3
DABCO (20 mol%)
DABCO (20 mol%)
DABCO (20 mol%)
DABCO (30 mol%)
DABCO (10 mol%)
10
a
Reaction conditions: hydrazine hydrate (1.2 mmol), ethyl acetoacetate (1.0 mmol), 4-nitrobenzaldehyde (1.0 mmol) and N-phenacylpyridinium bromide (1.0 mmol) in the presence of
different catalytic systems under various conditions.
b
See SAFETY CAUTION in Experimental
c
The reaction was tested at different microwave powers (100–300 W) at a range of temperatures (40–100 °C) in H O.
2
d
Isolated yields.

JOURNAL OF CHEMICAL RESEARCH 2018 221
a
Table 2 Domino one-pot two-step four-component synthesis of 4,5-dihydro-1H-furo[2,3-c]pyrazole derivatives
d
Entry
R
X
H
H
H
Product
6a
6b
6c
6d
6e
6f
6g
6h
Time (min)
Yield (%)
87
90
82
74
82
80
83
85
1
2
3
4
5
6
7
8
9
4-NO2
4-Cl
4-Me
4-OMe
2-Cl
4-CN
4-Cl-3-NO2
4-Me
2,4-(Cl)2
3,4-(OMe)2
10
10
12
12
10
10
10
12
10
12
H
Cl
Cl
Cl
Cl
Br
Br
6i
6j
88
76
10
a
Reaction conditions: hydrazine hydrate (1.2 mmol), ethyl acetoacetate (1.0 mmol), aromatic aldehyde (1.0 mmol), pyridinium salt (1.0 mmol) and DABCO (20 mol%) under microwave
irradiation (180 W, max. 70 °C) in H O (10 mL).
2
b
See SAFETY CAUTION in Experimental.
c
5
a, X = H; 5b, X = Cl; 5c, X = Br.
d
Isolated yields.
Scheme 2 Possible mechanism for the formation of 4,5-dihydro-1H-furo[2,3-c]pyrazole derivatives.

222 JOURNAL OF CHEMICAL RESEARCH 2018
may act as potential drug candidates, since pyrazole and furan
motifs have a range of biological activities.
(d, 2H, J = 8.1 Hz, ArH), 7.91–8.07 (m, 5H, ArH), 12.34 (s, 1H, NH)
13
ppm; C NMR (75 MHz, CDCl ): δ 13.8 and 20.5 (2CH ), 42.6 and
3
C
3
91.7 (2CH), 115.8, 121.2, 122.5, 126.8, 128.4, 128.9, 129.3, 130.1, 131.7,
Experimental
133.8, 138.6, 141.6 and 162.7 (Colefinic and Carom), 192.4 (C=O) ppm.
Anal. calcd for C H N O : C, 75.45; H, 5.70; N, 8.80; found: C, 75.72;
The chemicals used in this work were purchased from Merck and
Aldrich and used without further purification. All melting points were
determined on an Electrothermal 9100 apparatus and are uncorrected.
IR spectra were recorded on a Shimadzu IR-470 spectrometer.
Elemental analyses for C, H, and N were performed using a Costech
ECS 4010 CHNS-O analyser at the analytical laboratory of the Islamic
20 18
2
2
H, 5.49; N, 9.06%.
4-(4-Methoxyphenyl)-3-methyl-4,5-dihydro-1H-furo[2,3-c]
pyrazol-5-yl](phenyl)methanone (6d): Light yellow solid; yield
4% (0.247 g); m.p. 182–183 °C; IR (KBr): νmax 3218, 3069, 2936,
670, 1691, 1649, 1487, 1408, 1369, 1332, 1236, 1155, 1064, 987, 871,
[
7
2
–1
1
1
13
760 cm ; H NMR (300 MHz, CDCl ): δ 1.85 (s, 3H, CH ), 3.73
Azad University, Yazd Branch. The H and C NMR spectra were
3
H
3
(
s, 3H, OCH ), 5.03 (d, 1H, J = 4.8 Hz, CH), 5.98 (d, 1H, J = 4.8 Hz,
recorded in CDCl on a Bruker DRX-300 spectrometer operating
3
3
1
13
CH), 7.52–7.59 (m, 4H, ArH), 7.75–7.86 (m, 5H, ArH), 12.16 (s, 1H,
at 300 MHz for H analysis and 75 MHz for C analysis. Chemical
shifts (δ) are given in ppm and coupling constants (J) are given in
Hz. All reactions were carried out using a laboratory microwave
oven (MicroSYNTH, Milestone Company, Italy). Thin-layer
chromatography (TLC) was performed on silica-gel Polygram SILG/
UV 254 plates.
13
NH) ppm; C NMR (75 MHz, CDCl ): δ 13.8 (CH ), 43.9 (CH), 57.4
3
C
3
(
OCH ), 90.8 (CH), 117.5, 121.3, 122.4, 127.7, 128.3, 128.7, 130.3,
3
131.4, 132.5, 135.6, 141.4, 155.6 and 162.8 (Colefinic and Carom), 191.5
(
C=O) ppm. Anal. calcd for C H N O : C, 71.84; H, 5.43; N, 8.38;
20 18 2 3
found: C, 72.11; H, 5.19; N, 8.54%.
4-Chlorophenyl)[4-(2-chlorophenyl)-3-methyl-4,5-dihydro-1H-
(
CAUTION: Due precautions, including use of a good fume cupboard,
were taken with hydrazine hydrate due to its high toxicity.
furo[2,3-c]pyrazol-5-yl]methanone (6e): Light yellow solid; yield
82% (0.306 g); m.p. 228–230 °C; IR (KBr): νmax 3224, 3065, 2884,
2
659, 1683, 1647, 1482, 1411, 1356, 1312, 1233, 1148, 1074, 984, 869,
–1 1
Synthesis of novel 4,5-dihydro-1H-furo[2,3-c]pyrazole derivatives
756 cm ; H NMR (300 MHz, CDCl ): δ 1.91 (s, 3H, CH ), 4.87 (d,
3
H
3
(
6a–j); general procedure
1H, J = 4.5 Hz, CH), 5.92 (d, 1H, J = 4.8 Hz, CH), 7.44 (d, 2H, J = 8.1
Hz, ArH), 7.65 (d, 2H, J = 8.1 Hz, ArH), 7.85–7.97 (m, 4H, ArH), 12.26
13
A mixture of hydrazine hydrate (1) (1.2 mmol), ethyl acetoacetate (2)
1.0 mmol) and water (10 mL) was irradiated in a microwave oven at
80 W until, in less than 3 min, a white solid of pyrazolone (3) was
(s, 1H, NH) ppm; C NMR (75 MHz, CDCl ): δ 14.2 (CH ), 38.8 and
3 C 3
(
1
91.3 (2CH), 114.3, 122.5, 126.5, 127.4, 128.3, 128.6, 129.5, 130.3, 131.3,
132.5, 135.3, 140.3, 141.6 and 163.2 (Colefinic and Carom), 194.1 (C=O)
ppm. Anal. calcd for C H Cl N O : C, 61.14; H, 3.78; N, 7.51; found:
formed. The microwave was programmed to give a maximum
internal temperature of 70 °C. Then, the aryl aldehyde 4 (1.0 mmol),
the pyridinium salt 5 (1.0 mmol) and DABCO were added to the
above reaction mixture which was irradiated further at the same
temperature (180 W, max. 70 °C) for an appropriate time as shown in
Table 2. Upon completion of the reaction, monitored by TLC on SiO2
using EtOAc/hexane (1:1) as eluent, the reaction mixture was allowed
to cool to room temperature. Water (5 mL) was added to the mixture,
which was then filtered for separation of the crude product. This
was recrystallised from hot ethanol to give the pure product 6. The
spectroscopic and analytical data are presented below.
19
14
2
2
2
C, 61.38; H, 4.06; N, 7.34%.
4-[5-(4-Chlorobenzoyl)-3-methyl-4,5-dihydro-1H-furo[2,3-c]
pyrazol-4-yl]benzonitrile (6f): Light yellow solid; yield 80%
(0.290 g); m.p. 245–248 °C; IR (KBr): νmax 3225, 3072, 2936, 2662,
2204, 1687, 1647, 1475, 1424, 1356, 1315, 1237, 1151, 1078, 977, 854,
–1 1
758 cm ; H NMR (300 MHz, CDCl ): δ 1.85 (s, 3H, CH ), 5.11 (d,
3
H
3
1H, J = 4.5 Hz, CH), 5.87 (d, 1H, J = 4.5 Hz, CH), 7.37–7.45 (m, 4H,
13
ArH), 7.85–7.97 (m, 4H, ArH), 12.38 (s, 1H, NH) ppm; C NMR (75
MHz, CDCl ): δ 13.7 (CH ), 41.2 and 91.5 (2CH), 111.4, 114.2, 119.3,
3
C
3
124.5, 128.2, 128.6, 129.4, 130.2, 130.5, 131.7, 132.5, 138.2, 140.5,
145.4 and 162.8 (Colefinic and Carom), 192.7 (C=O) ppm. Anal. calcd for
C H ClN O : C, 66.03; H, 3.88; N, 11.55; found: C, 66.32; H, 4.11; N,
[3-Methyl-4-(4-nitrophenyl)-4,5-dihydro-1H-furo[2,3-c]pyrazol-5-
yl](phenyl)methanone (6a): Light yellow solid; yield 87% (0.304 g);
m.p. 208–210 °C; IR (KBr): νmax 3212, 3083, 2985, 2678, 1691, 1648,
1
2
0
14
3
2
11.69%.
–1 1
495, 1412, 1372, 1335, 1231, 1167, 1085, 994, 850, 758 cm ; H NMR
[4-(4-Chloro-3-nitrophenyl)-3-methyl-4,5-dihydro-1H-furo[2,3-c]
pyrazol-5-yl](4-chlorophenyl)methanone (6g): Light yellow solid;
yield 83% (0.347 g); m.p. 239–240 °C; IR (KBr): νmax 3236, 3112, 2934,
2672, 1688, 1648, 1482, 1436, 1352, 1326, 1245, 1153, 1072, 985, 867,
(300 MHz, CDCl ): δ 1.89 (s, 3H, CH ), 5.11 (d, 1H, J = 4.5 Hz, CH),
3
H
3
6
2
.02 (d, 1H, J = 4.5 Hz, CH), 7.54 (d, 2H, J = 7.8 Hz, ArH), 7.78 (d,
H, J = 7.8 Hz, ArH), 7.83–7.97 (m, 5H, ArH), 12.23 (s, 1H, NH) ppm;
C NMR (75 MHz, CDCl ): δ 14.1 (CH ), 43.4 and 91.3 (2CH), 115.4,
13
–1 1
756 cm ; H NMR (300 MHz, CDCl ): δ 1.82 (s, 3H, CH ), 5.08 (d,
3
C
3
3
H
3
1
1
20.4, 122.6, 127.2, 128.1, 128.4, 129.3, 130.1, 132.5, 138.4, 142.3,
45.7 and 161.7 (Colefinic and Carom), 191.5 (C=O) ppm. Anal. calcd for
1H, J = 4.8 Hz, CH), 6.12 (d, 1H, J = 4.8 Hz, CH), 7.45–8.14 (m, 7H,
13
ArH), 12.27 (s, 1H, NH) ppm; C NMR (75 MHz, CDCl ): δ 14.1
3 C
C H N O : C, 65.32; H, 4.33; N, 12.03; found: C, 65.58; H, 4.48; N,
(CH ), 40.4 and 92.3 (2CH), 114.7, 125.5, 126.7, 128.4, 129.3, 130.1,
19
15
3
4
3
1
2.31%.
4-(4-Chlorophenyl)-3-methyl-4,5-dihydro-1H-furo[2,3-c]pyrazol-
-yl](phenyl)methanone (6b): Light yellow solid; yield 90% (0.304 g);
131.7, 132.2, 132.8, 135.4, 138.5, 140.2, 141.2, 150.2 and 161.9 (Colefinic
and Carom), 192.5 (C=O) ppm. Anal. calcd for C H Cl N O : C, 54.56;
H, 3.13; N, 10.05; found: C, 54.25; H, 3.37; N, 10.41%.
[
19
13
2
3
4
5
m.p. 221–223 °C; IR (KBr): νmax 3207, 3073, 2991, 2672, 1688, 1647, 1491,
(4-Chlorophenyl)[3-methyl-4-(p-tolyl)-4,5-dihydro-1H-furo[2,3-c]
pyrazol-5-yl]methanone (6h): Light yellow solid; yield 85% (0.299
g); m.p. 217–219 °C; IR (KBr): νmax 3216, 3077, 2991, 2674, 1690, 1648,
–1
1
1
405, 1364, 1331, 1224, 1154, 1078, 981, 865, 762 cm ; H NMR (300
MHz, CDCl ): δ 1.91 (s, 3H, CH ), 5.16 (d, 1H, J = 4.5 Hz, CH), 5.94 (d,
3
H
3
–1 1
1
H, J = 4.5 Hz, CH), 7.36 (d, 2H, J = 8.1 Hz, ArH), 7.61 (d, 2H, J = 8.1
1492, 1422, 1375, 1334, 1256, 1137, 1078, 992, 847, 753 cm ; H NMR
13
Hz, ArH), 7.85–7.96 (m, 5H, ArH), 12.28 (s, 1H, NH) ppm; C NMR (75
(300 MHz, CDCl ): δ 1.86 (s, 3H, CH ), 2.21 (s, 3H, CH ), 5.12 (d,
3
H
3
3
MHz, CDCl ): δ 14.6 (CH ), 44.7 and 90.5 (2CH), 116.2, 120.8, 123.1,
1H, J = 4.5 Hz, CH), 5.97 (d, 1H, J = 4.5 Hz, CH), 7.43 (d, 2H, J = 8.1
3
C
3
127.5, 128.3, 128.8, 130.2, 130.7, 132.2, 137.3, 138.6, 141.7 and 162.6
Hz, ArH), 7.68 (d, 2H, J = 8.1 Hz, ArH), 7.93 (d, 2H, J = 7.7 Hz, ArH),
13
(
Colefinic and Carom), 192.7 (C=O) ppm. Anal. calcd for C H ClN O : C,
8.11–8.15 (m, 2H, ArH), 12.41 (s, 1H, NH) ppm; C NMR (75 MHz,
19
15
2
2
6
7.36; H, 4.46; N, 8.27; found: C, 67.71; H, 4.62; N, 8.45%.
3-Methyl-4-(p-tolyl)-4,5-dihydro-1H-furo[2,3-c]pyrazol-5-yl]
phenyl)methanone (6c): Light yellow solid; yield 82% (0.261 g); m.p.
14 °C; IR (KBr): νmax 3216, 3077, 2991, 2674, 1692, 1648, 1492, 1422,
CDCl ): δ 14.0 and 21.7 (2CH ), 44.2 and 90.3 (2CH), 113.7, 126.7, 126.9,
3
C
3
[
127.8, 128.2, 129.4, 129.8, 130.2, 131.5, 133.1, 137.5, 138.4, 140.2 and 162.8
(
2
(Colefinic and Carom), 191.8 (C=O) ppm. Anal. calcd for C H ClN O : C,
20
17
2
2
68.09; H, 4.86; N, 7.94; found: C, 68.45; H, 5.03; N, 7.81%.
–1 1
1375, 1334, 1256, 1137, 1078, 992, 847, 753 cm ; H NMR (300 MHz,
(4-Bromophenyl)[4-(2,4-dichlorophenyl)-3-methyl-4,5-dihydro-
1H-furo[2,3-c]pyrazol-5-yl]methanone (6i): Light yellow solid; yield
88% (0.398 g); m.p. 232–235 °C; IR (KBr): νmax 3214, 3085, 2973,
CDCl ): δ 1.87 (s, 3H, CH ), 2.18 (s, 3H, CH ), 5.14 (d, 1H, J = 4.8 Hz,
CH), 6.11 (d, 1H, J = 4.8 Hz, CH), 7.48 (d, 2H, J = 7.8 Hz, ArH), 7.72
3
H
3
3

JOURNAL OF CHEMICAL RESEARCH 2018 223
2
677, 1685, 1648, 1495, 1422, 1368, 1335, 1230, 1165, 1074, 983, 857,
8
9
B. Jiang, G. Zhang, N. Ma, F. Shi, S.-J. Tu, P. Kaur and G. Li, Org. Biomol.
Chem., 2011, 9, 3834.
R. Ghahremanzadeh, Z. Rashid, A.-H. Zarnani and H. Naeimi, J. Ind. Eng.
Chem., 2014, 20, 4076.
–1 1
760 cm ; H NMR (300 MHz, CDCl ): δ 1.89 (s, 3H, CH ), 5.21 (d,
3
H
3
1H, J = 4.5 Hz, CH), 5.87 (d, 1H, J = 4.5 Hz, CH), 7.58–7.64 (m, 4H,
ArH), 7.88 (s, 1H, ArH), 8.04–8.07 (m, 2H, ArH), 12.27 (s, 1H, NH)
ppm; C NMR (75 MHz, CDCl ): δ 14.6 (CH ), 41.5 and 91.7 (2CH),
1
0
E.C. Franklin, Chem. Rev., 1935, 16, 305.
13
3
C
3
11 F.W. Lichtenthaler, Acc. Chem. Res., 2002, 35, 728.
1
1
15.6, 124.6, 127.3, 128.7, 129.0, 129.4, 129.7, 130.1, 130.5, 132.4,
32.8, 135.2, 141.2 and 161.9 (Colefinic and Carom), 192.7 (C=O) ppm.
Anal. calcd for C H BrCl N O : C, 50.47; H, 2.90; N, 6.20; found: C,
12
V.A. Chebanov, E.A. Muravyova, S.M. Desenko, V.I. Musatov, I.V.
Knyazeva, S.V. Shishkina, O.V. Shishkin and C.O. Kappe, J. Combin.
Chem., 2006, 8, 427.
D. Das, R. Banerjee and A. Mitra, J. Chem. Pharm. Res., 2014, 6, 108.
G. Varvounis, Adv. Heterocycl. Chem., 2009, 98, 143.
A. Schmidt and A. Dreger, Curr. Org. Chem., 2011, 15, 1423.
S. Archana, R. Ranganathan, M. Dinesh, P. Arul, A. Ponnuswamy, P.
Kalaiselvi, S. Chellammal and G. Subramanian, Res. Chem. Intermed.,
2017, 43, 2471.
19
13
2
2
2
13
5
0.73; H, 3.24; N, 6.35%.
4-Bromophenyl)[4-(3,4-dimethoxyphenyl)-3-methyl-4,5-dihydro-
H-furo[2,3-c]pyrazol-5-yl]methanone (6j): Light yellow solid; yield
1
4
(
15
1
16
76% (0.337 g); m.p. 197–199 °C; IR (KBr): νmax 3225, 3067, 2881,
2
662, 1688, 1647, 1473, 1415, 1352, 1321, 1235, 1152, 1071, 984, 856,
–1 1
756 cm ; H NMR (300 MHz, CDCl ): δ 1.91 (s, 3H, CH ), 3.89 and
17 K.A. Kumar and M. Govindaraju, Int. J. ChemTech Res., 2015, 8, 313.
18 Ş.G. Küçükgüzel and S. Şenkardeş, Eur. J. Med. Chem., 2015, 97, 786.
3
H
3
3.91 (s, 6H, 2OCH ), 5.18 (d, 1H, J = 4.5 Hz, CH), 6.11 (d, 1H, J = 4.8
3
19 N.E. Shevchenko, Chem. Heterocycl. Compd., 1999, 35, 164.
Hz, CH), 7.43–7.47 (m, 4H, ArH), 7.85–7.91 (m, 3H, ArH), 12.31 (s,
13
20 D.S. Mortensen, A.L. Rodriguez, K.E. Carlson, J. Sun, B.S. Katzenellenbogen
and J.A. Katzenellenbogen, J. Med. Chem., 2001, 44, 3838.
21 S.M. Kupchan, M.A. Eakin and A.M. Thomas, J. Med. Chem., 1971, 14,
1147.
1H, NH) ppm; C NMR (75 MHz, CDCl ): δ 14.2 (CH ), 38.4 (CH),
3 C 3
55.3 and 55.8 (2OCH ), 91.6 (CH), 114.4, 116.2, 119.5, 120.1, 127.5,
3
128.4, 129.5, 130.4, 131.3, 131.5, 141.1, 147.2, 148.4 and 163.2 (Colefinic
and Carom), 191.8 (C=O) ppm. Anal. calcd for C H BrN O : C, 56.90;
H, 4.32; N, 6.32; found: C, 57.18; H, 4.63; N, 6.51%.
22 L.-C. Chou, L.-J. Huang, J.-S. Yang, F.-Y. Lee, C.-M. Teng and S.-C. Kuo,
Bioorg. Med. Chem., 2007, 15, 1732.
21
19
2
4
23
24
25
F.-Y. Lee, J.-C. Lien, L.-J. Huang, T.-M. Huang, S.-C. Tsai, C.-M. Teng, C.-
C. Wu, F.-C. Cheng and S.-C. Kuo, J. Med. Chem., 2001, 44, 3746
S. Bondock, W. Khalifa and A.A. Fadda, Eur. J. Med. Chem., 2011, 46,
555.
G. Broggini, L. Garanti, G. Molteni and G. Zecchi, Tetrahedron:
Asymmetry, 1999, 10, 487.
Acknowledgement
We gratefully acknowledge financial support from the Research
Council of the University of Science and Arts of Yazd, Iran.
.
2
Received 21 January 2018; accepted 31 March 2018
Paper 1805211
https://doi.org/10.3184/174751918X15241613654928
Published online: 23 April 2018
26 L. De Benassuti, L. Garanti and G. Molteni, Tetrahedron: Asymmetry,
004, 15, 1127.
I.M.A. Awad, Bull. Chem. Soc. Jpn., 1992, 65, 1652
A. Yazdani-Elah-Abadi, R. Mohebat and M.-T. Maghsoodlou, RSC Adv.,
016, 6, 84326.
A. Yazdani-Elah-Abadi, R. Mohebat and M. Kangani, J. Chem. Res., 2016,
0, 722.
2
2
2
7
8
.
2
29
References
4
1
G. Brahmachari, Green synthetic approaches for biologically relevant
heterocycles. Elsevier, Amsterdam, 2015.
30 R. Mohebat, A. Yazdani-Elah-Abadi, M.-T. Maghsoodlou and N. Hazeri,
Chin. Chem. Lett., 2017, 28, 943.
2
K.L. Ameta and A. Dandia, Green chemistry: synthesis of bioactive
heterocycles. Springer, New Delhi, India, 2014.
31 A. Yazdani-Elah-Abadi, S. Abbasi Pour, M. Kangani and R. Mohebat,
Monatsh. Chem., 2017, 148, 2135.
3
4
5
6
7
L.-R. Wen, S.-L. Li, J. Zhang and M. Li, Green Chem., 2015, 17, 1581.
H. Zhao, T. Zhang, T. Yan and M. Cai, J. Org. Chem., 2015, 80, 8849.
W. Yang, L. Wei, F. Yi and M. Cai, Tetrahedron, 2016, 72, 4059.
C.O. Kappe, Angew. Chem., Int. Ed., 2004, 43, 6250.
32 Q.-F. Wang, H. Hou, L. Hui and C.-G. Yan, J. Org. Chem., 2009, 74, 7403.
33 S. Majumder, M. Sharma and P.J. Bhuyan, Tetrahedron Lett., 2013, 54,
6868.
34 V.S. Tangeti, G.V. Siva Prasad, J. Panda and K.R. Varma, Synth.
Commun., 2016, 46, 878.
A.R. Bhat, A.H. Shalla and R.S. Dongre, J. Adv. Res., 2015, 6, 941.