An efficient synthesis of novel bis-chalcones and bis-pyrazolines in the presence of cellulose sulfuric acid as biodegradable catalyst under solvent-free conditions

Article abstract of DOI:10.5935/0103-5053.20140072

A highly efficient and practical approach for the synthesis of novel heterocyclic bis-chalcones and corresponding pyrazolines has been developed using cellulose sulfuric acid as environmentally benign, biodegradable and reusable catalyst under solvent-free conditions. The catalyst can be reused several times without significant loss of its catalytic activity.

Full text of DOI:10.5935/0103-5053.20140072

http://dx.doi.org/10.5935/0103-5053.20140072
J. Braz. Chem. Soc., Vol. 25, No. 6, 1002-1011, 2014.
Printed in Brazil - ©2014 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Article
A
An Efficient Synthesis of Novel Bis-Chalcones and Bis-Pyrazolines in the Presence
of Cellulose Sulfuric Acid as Biodegradable Catalyst under Solvent-Free Conditions
Zeba N. Siddiqui* and Tabassum Khan
Department of Chemistry, Aligarh Muslim University, 202002 Aligarh, India
Uma aproximação altamente eficiente e prática para a síntese de novas bis-chalconas
heterocíclicas e as pirazolinas correspondentes foi desenvolvida usando-se celulose sulfonada
como um catalisador ambientalmente benigno, biodegradável e reutilizável em condições livres
de solvente. O catalisador pode ser utilizado várias vezes sem perda significativa de sua atividade
catalítica.
A highly efficient and practical approach for the synthesis of novel heterocyclic bis-chalcones
and corresponding pyrazolines has been developed using cellulose sulfuric acid as environmentally
benign, biodegradable and reusable catalyst under solvent-free conditions. The catalyst can be
reused several times without significant loss of its catalytic activity.
Keywords: cellulose sulfuric acid, heterocyclic bis-chalcones, heterocyclic bis-pyrazolines,
heterogeneous catalysis
Introduction
Chalcones (1,3-diaryl/heteroaryl-2-propene-1-ones),
are important pharmacophores of various natural
products.1 The examples of approved therapeutic agents
incorporating this molecular framework include 3-methoxy-
4-hydroxyloncocarpin (NADH:ubiquinone oxidoreductase
activity inhibitor), xanthohumol (antioxidant) and
coumarin-chalcone (anticancer agents), respectively
(Figure 1). Many functionalized derivatives are also used
as antidiabetic, antitubulin, NO production inhibitor,
peritoneal antiangiogenic, antiproliferative agents and
probe to study protein-dye interactions.2-6
Figure 1. Biologically important chalcones.
They are generally synthesized via Claisen-Schmidt
condensation carried out in basic or acidic media under
homogeneous conditions in the presence of various
catalysts.7-12 However, in spite of their potential utility,
many of the reported methods suffer from certain
drawbacks like refluxing in hazardous organic solvents
for prolonged time, use of expensive and toxic catalysts,
high temperature and low product yields, harsh reaction
conditions with non-recyclable catalysts.
Heterogeneous solid acid catalysts have received special
attention as user-friendly catalysts due to environmental,
economic and industrial aspects. Due to good dispersion of
active reagent sites, associated selectivity and easier work-
up procedures, various organic reactions are performed
in the presence of heterogeneous catalysts and thus have
advantages over the conventional solution phase reactions.13
These catalysts are also advantageous over homogeneous
catalysts as they can be recovered and reused several times
to achieve very high turnover numbers, thereby making the
process economically viable.14 These days, science and
*e-mail: siddiqui_zeba@yahoo.co.in

Vol. 25, No. 6, 2014
Siddiqui and Khan
1003
technology is shifting emphasis on eco-friendly, natural
product resources and reusable catalysts. In this regard,
natural biopolymers are attractive candidates for solid
supported catalysis.15 Cellulose, one of the most abundant
natural biopolymers in the world, has been widely studied
during the past decades because it is both biodegradable
and a renewable resource. It is an attractive alternative to
conventional organic or inorganic supports in catalytic
applications due to its unique properties.16 It is extremely
inert, inexpensive, and have high hydrothermal stability.
Recently, cellulose sulfuric acid (CSA) has been employed
for the synthesis of thiadiazolo benzimidazoles, pyrroles,
1,4-dihydropyridines, 2,3-dihydroquinazolin-4-ones and
Ugi reaction.17-21
compounds was checked by thin layer chromatography
(TLC) on glass plates coated with silica gel G254
(E. Merck) using chloroform-methanol (3:1) mixture as
mobile phase and visualized by iodine vapours. XRD of the
catalyst were recorded in the 2θ range of 10-70° with scan
rate of 4° min-1 on a Rigaku Minifax X-ray diffractometer
with Ni-filtered Cu Kα radiation at a wavelength of
1.54060Å. The SEM-EDX characterization of the catalyst
was performed on a JEOL JSM-6510 scanning electron
microscope equipped with energy dispersive X-ray
spectrometer operating at 20 kV. TG/DTA was obtained
with DTG-60H, with a heating rate of 20 °C min-1 from
0 to 500 °C under N2 atmosphere.
Thus, based on the above findings and in continuation
of our interest in the development of efficient, economical
and new methodologies,22 we herein report, cellulose
sulfuric acid (CSA) as a biodegradable and recyclable solid
acid catalyst, for the synthesis of novel heterocyclic bis-
chalcones and bis-pyrazolines under thermal solvent-free
conditions in excellent yields.
The structure and morphology of the catalyst was
established for the first time with the help of powder X-ray
diffractograms (XRD), scanning electron microscopy
(SEM) and energy dispersion X-ray spectrometer
(EDX). The stability of the catalyst was evaluated by
thermogravimetric/differential thermal analysis (TG/DTA)
characterization techniques.
Preparation of cellulose sulfuric acid
Cellulose sulfuric acid was prepared by the dropwise
addition of chlorosulfonic acid (1.0 g, 9 mmol) to a
magnetically stirred mixture of cellulose (5.0 g) in n-hexane
(20 mL) at 0 °C during 2 h. HCl gas was removed from
the reaction vessel immediately. After the addition was
complete, the mixture was stirred for another 2 h. Then
the mixture was filtered, washed with 30 mL of acetonitrile
and dried at room temperature to afford 5.25 g of cellulose
sulfuric acid as a white powder. The number of H+ sites
on the cellulose-SO3H, determined by back titration, was
0.50 meq g-1.26
General procedure for the synthesis of bis-chalcones (3a-e)
Experimental
under solvent-free conditions
Melting points of all synthesized compounds were taken
in a Riechert Thermover instrument and are uncorrected.
The Fourier transform infrared (FT-IR) spectra (KBr) were
Terephthaldehyde 1 (1.00 mmol), 3-acetyl-4-
hydroxycoumarin/dehydroacetic acid/5-acetyl-1,3-
dimethylbarbituric acid/5-acetylbarbituric acid/5-
acetylthiobarbituric acid (2a-e) (2.00 mmol) and CSA
(0.06 g) were mixed thoroughly using a mortar and pestle,
transferred to an open pyrex 100 mL beaker and heated
at 70 °C for the given time (Table 1). After completion
of the reaction (monitored by TLC), the reaction mixture
was cooled to room temperature and added ethyl acetate
(5 mL). The reaction mixture was filtered to remove the
catalyst and concentrated to furnish pure products (3a-e).
1
recorded on Perkin Elmer RXI spectrometer. H nuclear
magnetic resonance (NMR) and 13C NMR spectra were
recorded on a Bruker DRX-300 and Bruker Avance II 400
spectrometer using tetramethylsilane (TMS) as an internal
standard and DMSO-d6/CDCl3 as solvent. Electrospray
ionization mass spectra (ESI-MS) were recorded on a
THERMO Finnigan LCQ Advantage max ion trap mass
spectrometer having an ESI source. Elemental analyses
(C, H and N) were conducted using the Elemental vario
EL III elemental analyzer and their results were found to
be in agreement with the calculated values. 3-Acetyl-4-
hydroxycoumarin, 5-acetyl-1,3-dimethyl barbituric acid,
5-acetyl-barbituric acid and 5-acetyl-thiobarbituric acid,23-25
were synthesized by reported procedures. Dehydroacetic
acid was purchased from E. Merck (Merck, Darmstadt,
Germany). Other chemicals were of commercial grade and
used without further purification. The homogeneity of the
2'E,2"E-3',3"-(1,4-Phenylene)bis(1-(4-hydroxy-1-
benzopyran-2-one-3-yl))prop-2-en-1-one (3a)
Yellow powder; mp > 300 °C; IR (KBr) νmax/cm-1 1620
1
(C=C), 1668 (C=O), 1719 (C=O), 3106 (OH); H NMR
(DMSO-d6, 400 MHz) d 7.07-7.15 (m, 8H, Ar-H), 7.41
(d, 2H, J 15.56 Hz, 2 Ha), 7.91 (d, 2H, J 15.68 Hz, 2 Hb),
7.56 (s, 4H, C6H4), 8.87 (s br, 2H, 2 OH); 13C NMR
(DMSO-d6, 100 MHz) d 103.05 (2 C-3), 115.53 (2 C-10),

1004
An Efficient Synthesis of Novel Bis-Chalcones and Bis-Pyrazolines
J. Braz. Chem. Soc.
Table 1. Synthesis of bis-chalconesa (3a-e) and their derived bis-
pyrazolinesb (5a-j)
(4 CH3), 86.21 (2 C-5), 122.89 (2 C-2'), 133.94, 136.01
(C6H4–C), 154.14 (2 C-3'), 162.97 (2 C-2), 176.63 (2 C-4,
C-6), 184.56 (2 C-1'); ESI-MS: m/z 495.3 (M+ + 1); anal.
calcd. for C24H22N4O8: C, 58.35; H, 4.45; N, 11.33; found:
C, 58.74; H, 4.84; N, 11.73.
entry
1
Product
3a
R
–
timec / min
Yieldd / %
98
3
4
6
9
9
3
3
4
4
6
6
7
6
7
8
2
3b
3c
–
98
3
–
96
2'E,2"E-3',3"-(1,4-Phenylene)bis(1-(2,4,6-pyrimidinetrione-
5-yl))prop-2-en-1-one (3d)
4
3d
3e
–
95
Yellow powder; mp > 300 °C; IR (KBr) νmax/cm-1 1628
5
–
95
1
(C=C), 1676 (C=O), 1700 (C=O), 3173 (NH); H NMR
6
5a
H
Ph
H
Ph
H
Ph
H
Ph
H
Ph
98
(DMSO-d6, 400 MHz) d 7.72 (d, 2H, J 15.52 Hz, 2 Ha),
7.75-7.93 (m, 4H, C6H4), 8.35 (d, 2H, J 15.04 Hz, 2 Hb),
10.00 (s, 4H, 4 NH); 13C NMR (DMSO-d6, 100 MHz) d
90.40 (2 C-5), 122.03 (2 C-2'), 129.90, 135.59 (C6H4–C),
152.92 (2 C-3’), 163.98 (2 C-2), 177.35 (2 C-4, C-6),
185.01 (2 C-1’); ESI-MS: m/z 439.2 (M+ + 1); anal. calcd.
for C20H14N4O8: C, 54.84; H, 3.19; N, 12.78; found: C,
55.04; H, 3.39; N, 12.98.
7
5b
5c
97
8
98
9
5d
5e
97
10
11
12
13
14
15
96
5f
95
5g
95
5h
5i
96
96
2'E,2"E-3',3"-(1,4-Phenylene)bis(1-(2-mercapto-4,6-
pyrimidinedione-5-yl))prop-2-en-1-one (3e)
5j
95
aReaction conditions: terephthaldehyde (1, 1.00 mmol); different cyclic
active methyl compounds (1a-e, 2.00 mmol); CSA (0.06 g); solvent-free
conditions; 70 °C; breaction conditions: bis-chalcones (3a-e, 1.00 mmol);
hydrazines (4a-b, 2.00 mmol); CSA (0.06 g); solvent-free conditions;
70 °C; creaction progress monitored by TLC; disolated yields.
Orange solid; mp > 300 °C; IR (KBr) νmax/cm-1 1151
(C=S), 1606 (C=C), 1665 (C=O), 1716 (C=O), 3105 (NH);
1H NMR (DMSO-d6, 400 MHz) d 7.55-8.14 (m, 8H, 4H,
C6H4, 2 Ha and 2 Hb), 9.97 (s, 2H, 2 NH), 10.86 (s br, 2H,
2 NH); 13C NMR (DMSO-d6, 100 MHz) d 88.43 (2 C-5),
123.13 (2 C-2'), 128.18, 132.37(C6H4–C), 153.12 (2 C-3'),
162.51 (2 C-2), 166.89 (2 C-4, C-6), 187.01 (2 C-1');
ESI-MS: m/z 471.2 (M+ + 1); anal. calcd. for C20H14N4O6: C,
51.11; H, 2.89; N, 11.91; found: C, 50.81; H, 2.59; N, 11.61.
122.16 (2 C-2’), 122.50, 125.52, 127.88, 130.73, 131.60,
135.57, 136.63 (Ar–C, C6H4–C), 153.51 (2 C-3'), 163.81
(2 C-2), 176.62 (2 C-4), 188.66 (2 C-1'); ESI-MS: m/z
507.0 (M+ + 1); anal. calcd. for C30H18O8: C, 71.21; H, 3.56;
found: C, 70.81; H, 3.16.
2'E,2"E-3",3"-(1,4-Phenylene)bis(1-(4-hydroxy-6-methyl-2-
oxo-2H-pyran-3-yl))prop-2-en-1-one (3b)
General procedure for the synthesis of bis-pyrazolines (5a-j)
under solvent-free conditions
Pale yellow solid; mp > 300 °C; IR (KBr) νmax/cm-1 1636
1
(C=C), 1695 (C=O), 1723 (C=O), 3106 (OH); H NMR
The compound 3a-e (1.00 mmol) and hydrazines
(hydrazine hydrate (2.00 mmol)/phenyl hydrazine
(2.00 mmol)) and CSA (0.06 g) were mixed well and
heated at 70 °C in a 100 mL beaker. After completion of
the reaction (monitored by TLC), the reaction mixture was
cooled to room temperature and added ethyl acetate (5 mL).
The reaction mixture was filtered to remove the catalyst and
concentrated to furnish pure products 5a-j.
(CDCl3, 400 MHz) d 2.41 (s, 6H, 2 CH3), 6.00 (s, 2H, 2
H5), 7.72 (d, 2H, J 13.08 Hz, 2 Ha), 7.92 (s, 4H, C6H4,), 8.41
(d, 2H, J 16.08 Hz, 2 Hb); 13C NMR (DMSO-d6, 100 MHz)
d 19.89 (2 CH3), 95.11 (2 C-3), 104.95 (2 C-5), 122.31
(2 C-2'), 127.01, 132.39 (C6H4–C), 153.29 (2 C-3’), 162.5
(2 C-6), 164.9 (2 C-2), 167.01 (2 C-1’), 185.35 (2 C-4);
ESI-MS: m/z 435.1 (M+ + 1); anal. calcd. for C24H18O8: C,
66.42; H, 4.15; found: C, 66.03; H, 3.77.
5',5"-(1,4-Phenylene)bis(3-(4-hydroxy-1-benzopyran-2-one-
3-yl))pyrazoline (5a)
2'E,2"E-3',3"-(1,4-Phenylene)bis(1-(1,3-dimethyl-2,4,6-
pyrimidinetrione-5-yl))prop-2-en-1-one (3c)
Light green solid; mp > 300 °C; IR (KBr) νmax/cm-1 1314
(C–N), 1612 (C=N), 1676 (C=O), 3201 (NH), 3257 (OH);
1H NMR (DMSO-d6, 400 MHz) d 3.41 (dd, 2H, J 18.68,
9.8 Hz, 2 Hd), 4.13 (dd, 2H, J 18.5, 9.9 Hz, 2 Hc), 4.90 (m,
2H, 2 He), 7.22-7.95 (m, 12H, 8 Ar–H and 4H C6H4), 8.24
(s, 2H, 2 NH); 13C NMR (DMSO-d6, 100 MHz) d 44.85
Light yellow solid; mp > 300 °C; IR (KBr)
ν
max/cm-1 1620 (C=C), 1673 (C=O), 1725 (C=O); 1H NMR
(DMSO-d6, 400 MHz) d 3.33 (s, 12H, 4 N–CH3), 7.77-7.92
(m, 4H, C6H4), 8.32 (d, 2H, J 14.72 Hz, 2 Ha), 8.47 (d, 2H,
J 13.96 Hz, 2 Hb); 13C NMR (DMSO-d6, 100 MHz) d 26.81

Vol. 25, No. 6, 2014
Siddiqui and Khan
1005
(2 C-5'), 59.62 (2 C-4'), 95.48 (2 C-3), 113.18, 116.42,
119.55,120.78, 123.41, 125.23, 128.10, 131.07 (Ar–C,
C6H4-C), 153.61 (2 C-3'), 170.18 (2 C-2), 180.41 (2 C-4);
ESI-MS: m/z 535.1 (M+ + 1); anal. calcd. for C30H22N4O6: C,
67.47; H, 4.12; N, 10.48; found: C, 67.37; H, 4.02; N, 10.38.
5',5"-(1,4-Phenylene)bis(3-(1,3-dimethyl-2,4,6-pyrimidine-
trione-5-yl))pyrazoline (5e)
Light greenish powder; mp > 300 °C; IR (KBr)
ν
max/cm-1 1260 (C–N), 1626 (C=N), 1709 (C=O), 3212
1
(NH); H NMR (DMSO-d6, 400 MHz) d 3.24 (s, 12H,
4 N–CH3), 3.47 (dd, 2H, J 18.50, 8.00 Hz, 2 Hd), 4.03
(dd, 2H, J 18.5, 9.48 Hz, 2 Hc), 4.77 (m, 2H, 2 He), 7.38
(s, 4H, C6H4), 8.22 (s, 2H, 2 NH); 13C NMR (DMSO-d6,
100 MHz) d 27.08 (4 CH3), 46.55 (2 C-5'), 58.62 (2 C-4'),
97.68 (2 C-5), 126.48, 130.41 (C6H4–C), 151.28 (2 C-3'),
168.78 (2 C-2), 179.05 (2 C-4, C-6); ESI-MS: m/z 523.1
(M+ + 1); anal. calcd. for C24H26N8O6: C, 55.22; H, 4.98;
N, 21.45; found: C, 55.52; H, 4.88; N, 21.05.
1',1″-Phenyl-5',5"-(1,4-phenylene)bis(3-(4-hydroxy-1-
benzopyran-2-one-3-yl))pyrazoline (5b)
Dark yellow solid; mp > 300 °C; IR (KBr) νmax/cm-1
1326 (C–N), 1620 (C=N), 1708 (C=O), 3406 (OH);
1H NMR (DMSO-d6, 400 MHz) d 3.41 (dd, 2H, J 9.24, 5.8
Hz, 2 Hd), 4.22 (dd, 2H, J 18.50, 12.12 Hz, 2 Hc), 5.42
(m, 2H, 2 He), 6.72-8.02 (m, 22H, 18Ar–H and 4H C6H4);
13C NMR (DMSO-d6, 100 MHz) d 44.02 (2 C-5'), 59.49
(2 C-4′), 99.19 (2 C-3), 111.49, 116.03, 116.49, 119.12,
121.11, 125.25, 126.59, 128.40, 131.07, 133.77, 136.28,
138.89 (Ar–C, C6H4–C), 149.93 (2 C-3'), 171.50 (2 C-2),
178.91 (2 C-4); ESI-MS: m/z 687.3 (M+ + 1); anal. calcd.
for C42H30N4O6: C, 73.53; H, 4.37; N, 8.16; found: C, 73.23;
H, 4.07; N, 7.86.
1',1"-Phenyl-5',5"-(1,4-phenylene)bis(3-(1,3-dimethyl-2,4,6-
pyrimidinetrione-5-yl))pyrazoline (5f)
Green solid; mp > 300 °C; IR (KBr) νmax/cm-1 1237
1
(C–N), 1650 (C=N), 1738 (C=O); H NMR (DMSO-d6,
400 MHz) d 3.10 (s, 12H, 4 N–CH3), 3.73 (dd, 2H, J 19.40,
4.36 Hz, 2 Hd), 4.05 (dd, 2H, J 19.1, 9.8 Hz, 2 Hc), 5.06
(m, 2H, 2 He), 6.88-7.50 (m, 14H, 10Ar–H and 4H C6H4);
13C NMR (DMSO-d6, 100 MHz) d 27.23 (4 CH3), 45.16
(2 C-5'), 63.03 (2 C-4'), 99.48 (2 C-5), 116.08, 129.05,
133.18, 134.64, 142.02 (Ar–C, C6H4–C), 166.01 (2 C-3'),
173.18 (2 C-2), 177.71 (2 C-4,C-6); ESI-MS: m/z 675.3
(M+ + 1); anal. calcd. for C36H34N8O6: C, 64.15; H, 5.04;
N, 16.61; found: C, 63.95; H, 4.84; N, 16.41.
5',5"-(1,4-Phenylene)bis(3-(4-hydroxy-6-methyl-2-oxo-2H-
pyran-3-yl))pyrazoline (5c)
Dark yellow powder; mp > 300 °C; IR (KBr)
ν
max/cm-1 1312 (C–N), 1650 (C=N), 1689 (C=O), 3208
1
(NH); H NMR (DMSO-d6, 400 MHz) d 2.12 (s, 6H, 2
CH3), 3.21 (dd, 2H, J 18.24, 9.88 Hz, 2 Hd), 3.89 (dd, 2H,
J 18.28, 10.16 Hz, 2 Hc), 4.79 (m, 2H, 2 He), 5.87 (s, 2H,
2 H5), 7.36 (s, 4H, C6H4), 8.19 (s, 2H, 2 NH); 13C NMR
(DMSO-d6, 100 MHz) d 19.44 (2 CH3), 43.40 (2 C-5′),
59.46 (2 C-4'), 99.12 (2 C-3), 103.63 (2 C-5), 126.62,
132.02 (C6H4–C), 153.69 (2 C-3′), 169.72 (2 C-6), 174.31
(2 C-2), 179.45 (2 C-4); ESI-MS: m/z 463.1 (M+ + 1); anal.
calcd. for C24H22N4O6: C, 62.39; H, 4.76; N, 12.12; found:
C, 61.99; H, 5.06; N, 11.92.
5',5"-(1,4-Phenylene)bis(3-(2,4,6-pyrimidinetrione-5-yl))
pyrazoline (5g)
Yellow powder; mp > 300 °C; IR (KBr) νmax/cm-1 1268
(C–N), 1634 (C=N), 1709 (C=O), 3121 (NH), 3216 (NH);
1H NMR (DMSO-d6, 400 MHz) d 3.47(dd, 2H, J 18.56, 8.04
Hz, 2 Hd), 4.03 (dd, 2H, J 18.16, 9.48 Hz, 2 Hc), 4.73 (m, 2H,
2 He), 7.38 (s, 4H, C6H4), 10.89 (s, 2H, 2 NH), 12.10 (s, 4H, 4
NH); 13C NMR (DMSO-d6, 100 MHz) d43.92 (2 C-5'), 55.62
(2 C-4'), 95.92 (2 C-5), 126.62, 130.12 (C6H4–C), 149.30
(2 C-3'), 166.65 (2 C-2), 179.01 (2 C-4, C-6); ESI-MS: m/z
467.2 (M+ + 1); anal. calcd. for C20H18N8O6: C, 51.54; H,
3.86; N, 24.03; found: C, 51.14; H, 3.56; N, 23.73.
1',1"-Phenyl-5',5"-(1,4-phenylene)bis(3-(4-hydroxy-6-
methyl-2-oxo-2H-pyran-3-yl))pyrazoline (5d)
Dark yellow solid; mp > 300 °C; IR (KBr) νmax/cm-1
1339 (C–N), 1649 (C=N), 1713 (C=O), 3423 (OH);
1H NMR (DMSO-d6, 400 MHz) d 2.26 (s, 6H, 2 CH3),
3.32 (dd, 2H, J 18.88, 12.88 Hz, 2 Hd), 4.10 (dd, 2H, J
18.84, 12.28 Hz, 2 Hc), 5.28 (m, 2H, 2 He), 6.22 (s, 2H,
2 H5), 6.73-7.30 (m, 14H, 10Ar–H and 4H C6H4), 13.07
(s, 2H, 2 OH); 13C NMR (DMSO-d6, 100 MHz) d 19.58 (2
CH3), 45.90 (2 C-5'), 61.73 (2 C-4'), 94.08 (2 C-3), 100.52
(2 C-5), 112.68, 119.38, 126.68, 135.42 (Ar–C, C6H4–C),
141.22 (2 C-3'), 161.25 (2 C-6), 163.41 (2 C-2), 183.12
(2 C-4); ESI-MS: m/z 615.2 (M+ + 1); anal. calcd. for
C36H30N4O6: C, 70.42; H, 4.89; N, 9.12; found: C, 70.62;
H, 4.99; N, 9.02.
1',1"-Phenyl-5',5"-(1,4-phenylene)bis(3-(2,4,6-pyrimidine-
trione-5-yl))pyrazoline (5h)
Orange solid; mp > 300 °C; IR (KBr) νmax/cm-1 1260
1
(C–N), 1622 (C=N), 1721 (C=O), 3184 (NH); H NMR
(DMSO-d6, 400 MHz) d 6.78 (dd, 2H, J 8.60, 7.28 Hz,
2 Hd), 6.86 (m, 2H, 2 He), 7.25 (dd, 2H, J 15.96, 8.16 Hz,
2 Hc), 7.66-8.48 (m, 14H, 10Ar–H and 4H C6H4), 10.60 (s,
2H, 2 NH), 11.09 (s, 2H, 2 NH), 17.09 (s, 2H, 2 OH, D2O
exchangeable); 13C NMR (DMSO-d6, 100 MHz) d 47.90
(2 C-5'), 65.21 (2 C-4'), 94.04 (2 C-5), 112.22, 119.18,

1006
An Efficient Synthesis of Novel Bis-Chalcones and Bis-Pyrazolines
J. Braz. Chem. Soc.
Figure 2. FT-IR spectra of cellulose sulfuric acid.
peaks from 1162-1058 cm-1 and at 898 cm-1 represented
C–O stretching, C–C skeletal vibrations, and C1–H ring
stretching of the glucose unit, respectively. For sulfonic
acid functional group, the peaks at 1162 and 1058 cm-1
of O=S=O group (asymmetric and symmetric stretching
modes) had merged with the peaks of C–O stretching and
C–C skeletal vibrations of glucose unit of cellulose moiety,
whereas the peak for S–O stretching mode was present at
662 cm-1.27
125.99, 129.18, 135.07, 144.75 (Ar–C, C6H4–C), 149.02,
149.71 (2 C-3'), 174.85 (2 C-2), 181.99 (2 C-4, C-6);
ESI-MS: m/z 619.1 (M+ + 1); anal. calcd. for C32H26N8O6: C,
62.19; H, 4.21; N, 18.12; found: C, 62.39; H, 4.41; N, 18.32.
5',5"-(1,4-Phenylene)bis(3-(2-mercapto-4,6-pyrimidine-
dione-5-yl))pyrazoline (5i)
Orange solid; mp > 300 °C; IR (KBr) νmax/cm-1 1151
(C=S), 1269 (C–N), 1629 (C=N), 1740 (C=O), 3180 (NH),
Powder XRD (Figure 3) of CSA showed characteristic
diffraction peaks for cellulose moiety at 16.5, 22.5 and
34.5°.28
1
3220 (NH); H NMR (DMSO-d6, 400 MHz) d 3.17 (dd,
2H, J 18.76, 11.44 Hz, 2 Hd), 3.61 (dd, 2H, J 18.4, 12.92
Hz, 2 Hc), 4.27 (m, 2H, 2 He), 7.39 (s, 4H, C6H4), 9.99
(s, 2H, 2 NH), 10.89 (s, 4H, 4 NH); 13C NMR (DMSO-d6,
100 MHz) d 42.02 (2 C-5'), 64.09 (2 C-4'), 99.48 (2 C-5),
126.62, 128.50 (C6H4–C), 160.53 (2 C-3'), 162.13 (2 C-4,
C-6), 176.16 (2 C-2); ESI-MS: m/z 499.2 (M+ + 1); anal.
calcd. for C20H18N8O4S2 C, 48.23; H, 3.61; N, 22.49; found:
C, 47.93; H, 3.31; N, 22.19.
1',1"-Phenyl-5',5"-(1,4-phenylene)bis(3-(2-mercapto-4,6-
pyrimidinedione-5-yl))pyrazoline (5j)
Green solid; mp > 300 °C; IR (KBr) νmax/cm-1 1141
(C=S), 1256 (C–N), 1630 (C=N), 1729 (C=O), 3264 (NH);
1H NMR (DMSO-d6, 400 MHz) d 5.06 (dd, 2H, J 14.88,
6.96 Hz, 2 Hd), 6.77 (dd, 2H, J 15.6, 7.8 Hz, 2 Hc), 7.09
(m, 2H, 2 He), 7.15-7.83 (m, 14H, 10Ar–H and 4H C6H4),
11.62 (s, 4H, 4 NH); 13C NMR (DMSO-d6, 100 MHz)
d 43.85 (2 C-5'), 59.79 (2 C-4'), 99.49 (2 C-5), 120.01,
123.96, 128.86, 132.07, 137.69, 142.53 (Ar–C, C6H4–C),
152.04 (2 C-3'), 178.12 (2 C-4, C-6), 181.03 (2 C-2); ESI-
MS: m/z 651.1 (M+ + 1); anal. calcd. for C32H26N8S2O6: C,
59.13; H, 4.99; N, 17.23; found: C, 58.73; H, 4.59; N, 16.83.
Figure 3. The powder XRD pattern of fresh catalyst.
The SEM images of CSA (Figure 4) showed smooth,
compact and homogeneous fibrous surface.
EDX analysis (Figure 5) of CSA showed peaks for C,
O and S elements.
To evaluate thermal stability of CSA, TG and DTA
experiments were carried out and the thermograms are
illustrated in Figure 6. For TG and DTA analysis the sample
was heated up to 500 °C at a constant rate of 20 °C min-1
in the nitrogen atmosphere. The weight losses found from
TG analysis measurements agreed fairly well with those
expected for the decomposition of cellulose sulfuric acid
to cellulose and sulfuric acid group. For this catalyst, the
Results and Discussion
Characterization of the cellulose sulfuric acid (CSA)
The FT-IR spectrum of the catalyst (Figure 2) exhibited
a broad peak for OH group at 3100-3600 cm-1. The

Vol. 25, No. 6, 2014
Siddiqui and Khan
1007
Figure 4. SEM images of the catalyst (CSA) at different magnifications.
Figure 5. EDX analysis of the catalyst (CSA).
thermo gravimetric curve seems to indicate three-stage
decomposition which was due to removal of physically
adsorbed water (70-100 °C). Decomposition of the sulfonic
functional group with rapid evolution of SO3 or SO2 between
200-330 °C took place and further gradually up to 500 °C
which may be due to decomposition of cellulose showing
mass loss of 34%. DTA measurement was performed in order
to provide further evidence for the presence of the various
species and evaluated their thermal behaviour (Figure 6). In
the curve, the endothermic peak at lower temperature showed
the removal of the physically adsorbed water from the
material, while the endothermic peaks at higher temperatures
(250 °C, 500 °C) represented the decomposition of cellulose
sulfuric acid to cellulose and sulfuric acid group.
Figure 6. TG/DTA graph of cellulose sulfuric acid.
group of propenone moiety appeared as strong and sharp
absorption band at 1668 cm-1 whereas band at 1620 cm-1 was
assigned to carbon-carbon double bond of α,β-unsaturated
1
system. The H NMR spectrum showed trans olefinic
protons Ha and Hb as ortho coupled doublets at d 7.41
(J = 15.56 Hz) and d 7.91 (J = 15.68 Hz), respectively.
All other protons were present at their normal values. The
13C NMR spectrum showed signal at d 188.66 for α,β
unsaturated carbonyl group whereas olefinic carbons C-2’
and C-3’were present at d 122.16 and 153.51, respectively.
The other carbon signals appeared at their appropriate
positions. Mass spectrum of 3a showed molecular ion as
M+ + 1 peak at m/z 507. A plausible mechanism for the
formation of (3a-e) is depicted in Scheme 2.
Synthesis of bis-chalcones (3a-e)
The synthesis of bis-chalcones (3a-e) was performed
in a manner as outlined in Scheme 1. The structure of
isolated bis-chalcones was verified by elemental analyses
Synthesis of bis-pyrazolines (5a-j)
Bis-pyrazolines (5a-j) were synthesized employing
(3a-e) (1.00 mmol) with hydrazine derivatives (4a-b)
(2.00 mmol) in the presence of CSA under same reaction
conditions (Scheme 1) (Table 1). The IR spectrum of 5a
showed two broad absorption bands at 3257 and 3201 cm-1
1
and spectroscopic data (FT-IR, H NMR, 13C NMR and
MS). The infrared (IR) spectrum of 3a exhibited the broad
band for OH group at 3106 cm-1 and a sharp, strong band
at 1719 cm-1 for coumarin carbonyl group. The carbonyl

1008
An Efficient Synthesis of Novel Bis-Chalcones and Bis-Pyrazolines
J. Braz. Chem. Soc.
Scheme 1. Synthetic route of bis-chalcones (3a-e) and bis-pyrazolines (5a-j).
Scheme 2. Plausible mechanism for the synthesis of bis-chalcones (3a-e).
due to the presence of OH group of coumarin and NH
group of pyrazoline moieties respectively whereas carbonyl
absorption band for coumarin moiety was discernible at
1676 cm-1. The absorbtion bands at 1612, 1314 cm-1 were
assigned to C=N, C–N groups of pyrazoline moiety. In the
1H NMR spectrum the presence of pyrazoline moiety was
manifested by two doublets of doublets at d 3.41 (Hd),
4.13 (Hc) and a multiplet at d 4.90 (He). The NH proton
of pyrazoline unit appeared as broad singlet at d 8.24. The
13C NMR spectrum showed signals at d 44.85, 59.62, and
153.61 for C-5', C-4', and C-3' carbons of pyrazolines moiety
respectively. The other peaks were present at their normal
values and are mentioned in the experimental section. The
mass spectrum of 5a showed M+ + 1 at m/z 535.1.A plausible
mechanismfortheformationof(5a-j)isdepictedinScheme 3.
Catalytic activity of CSA
The catalytic activity of CSA was explored by pursuing
the synthesis of bis-chalcones and bis-pyrazolines. For
optimization of appropriate reaction conditions, the reaction
of terephthaldehyde (1) (1.00 mmol) with 3-acetyl-4-
hydroxycoumarin (2a) (2.00 mmol) in the presence of
CSA (0.06 g) under solvent-free conditions at 70 °C were
chosen as a model reaction.
Solvent effect
We investigated the effect of different solvents in
comparison with solvent-free condition on the reaction rate
as well as yields of the products (Table 2). The data revealed

Vol. 25, No. 6, 2014
Siddiqui and Khan
1009
Scheme 3. Plausible mechanism for the synthesis of bis-pyrazolines (5a-j).
that maximum yield of the product (98%) in very short
time period (3 min) was obtained only under solvent-free
condition at 70 °C.
sulfuric acid > silica-sulfamic acid > p-toluene sulfonic
acid > sulfuric acid in acetic acid. Thus, cellulose sulfuric
acid is a more efficient and superior catalyst over other acidic
catalysts in terms of time, yield and reaction condition.
Table 2. Effect of various solvents versus the solvent-free condition for
the model reactiona
Table 3. Comparison of catalytic activity of different catalysts for the
model reactiona
Temperature /
°C
timeb /
min
Yieldc /
%
entry
Solvent
entry
1
Catalyst
Cellulose-sulfuric acid
PEG-sulfuric acidd
Camphor-sulfonic acidd
Silica-sulfuric acidd
NaHSO4-silicad
timeb / min
Yieldc / %
1
THF
CH3CN
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
25
1800
1440
960
780
330
300
480
390
420
240
210
72
27
3
48
78
120
84
90
144
90
168
–
98
2
35
2
81
3
CHCl3
44
3
77
4
CH2Cl2
47
4
76
5
EtOH
65
5
73
71
6
MeOH
60
6
Xanthan-sulfuric acidd
Silica-sulfamic acidd
p-Toluene sulfonic acide
Sulfuric acid in acetic acide
Sulfamic acide
7
Isopropanol
Acetic acid
H2O
53
7
69
8
72
8
68
9
41
9
57
10
11
12
13
14
15
PEG-400
Glycerol
Solvent-free
Solvent-free
Solvent-free
Solvent-free
54 (mixture)
10
11
12
13
Incomplete
Incomplete
Incomplete
65 (mixture)
Sulfanilic acide
–
17
86
98
96
Cellulosed
–
60
10
No catalyst
No reaction No reaction
70
3
aReaction conditions: terephthaldehyde (1, 1.00 mmol); 3-acetyl-4-
hydroxycoumarin (2a, 2.00 mmol); catalyst (0.06 g); solvent-free
condition; 70 °C; breaction progress monitored by TLC; cisolated yields;
d0.120 g of catalyst; e0.1 mmol of catalyst.
80
3
aReaction conditions: terephthaldehyde (1, 1.00 mmol); 3-acetyl-4-
hydroxycoumarin (2a, 2.00 mmol); catalyst (0.06 g); breaction progress
monitored by TLC; cisolated yields.
Effect of amount of CSA
Comparison of CSA with other catalysts
Generally, the rate of reaction and yield increases over
the amount of catalyst. To optimize the reaction conditions,
the model reaction was studied in the presence of varying
amounts of catalyst (Figure 7). In order to obtain the best
result, the optimum amount of catalyst turned out to be
0.06 g. On increasing the loading to 0.08 g, no significant
In order to show the superiority of CSA, other sulfur
analog acid catalysts were also used for the synthesis of 3a
(Table 3). The study revealed that the order of reactivity of
various catalysts was PEG-sulfuric acid > camphor-sulfonic
acid > silica-sulfuric acid > NaHSO4-silica > xanthan-

1010
An Efficient Synthesis of Novel Bis-Chalcones and Bis-Pyrazolines
J. Braz. Chem. Soc.
improvement in the yield was observed, whereas,
decreasing the amount of catalyst to 0.04 g resulted in
lowering of the yield.
Figure 8. Recycling data of CSA for model reaction.
Figure 7. Effect of catalyst loading on the model reaction.
Reusability of CSA
The reusability of the catalyst under solvent-free
condition was evaluated using model reaction of
terephthaldehyde (1) with 3-acetyl-4-hydroxycoumarin
(2a) in the presence of CSA (0.06 g) (Figure 8). After
completion of the reaction, the catalyst was recovered by
filtration and was than reused for eight cycles adopting the
identical protocol with a minor loss of catalytic activity.
The identity of the recovered catalyst was checked by
powder XRD (Figure 9) and SEM analysis (Figure 10). The
XRD pattern was similar to that of fresh catalyst with some
low intensity of peaks which may be due to the catalyst
deactivation after eight runs. The SEM image revealed intact
morphology after eight runs. These data establish that CSA
is not damaged upon its reuse as a heterogeneous catalyst.
Under these optimized reaction conditions the scope and
generality of the current protocol was further demonstrated
Figure 9. Powder XRD pattern of recovered catalyst after eight runs.
by the reaction of terephthaldehyde (1) with different
cyclic active methyl compounds (2a-e) under solvent-free
conditions. All the reactions proceeded smoothly and
the reaction was completed within 3-9 min to afford the
products (3a-e) in excellent yields (95-98%) (Table 1).
Conclusion
In conclusion, we have developed an expedient,
highly efficient, atom economical and simple protocol
for the synthesis of novel heterocyclic bis-chalcones and
Figure 10. SEM image of recovered catalyst after eight runs.

Vol. 25, No. 6, 2014
Siddiqui and Khan
1011
corresponding pyrazoline derivatives in excellent yields
using cellulose sulfuric acid as an inexpensive biopolymer-
based solid acid catalyst under solvent-free conditions.
Prominent advantages of this green method are broad
scope, operational simplicity, practicability, excellent
yields, shorter reaction time, economic viability, easy work-
up, and recyclability of the catalyst. We believe that this
protocol will be a more practical alternative to the other
existing methods.
A. F.; Gozzo, F. C.; Silva, W. A.; Neto, B. A. D.; Org. Biomol.
Chem. 2013, 11, 4764.
7. Dhar, D. N.; Chemistry of Chalcones and Related Compounds,
2nd ed.; Wiley-VCH: New York, USA, 1981.
8. Mobinikhaledi,A.; Kalhor, M.; Jamalifar, H.; Med. Chem. Res.
2012, 21, 1811.
9. Jahng, Y.; Zhao, L.-X.; Moon, Y.-S.; Basnet, A.; Kim, E.-K.;
Chang, H. W.; Ju, H. K.; Jeong, T. C.; Lee, E.-S.; Bioorg. Med.
Chem. Lett. 2004, 14, 2559.
10. Climent, M. J.; Corma, A.; Iborra, S.; Velty, A.; J. Catal. 2004,
221, 474.
Supplementary Information
11. Sebti, S.; Solhy, A.; Smahi, A.; Kossir, A.; Oumimoun, H.;
Catal. Commun. 2002, 3, 335.
Supplementary data are available free of charge at
http://jbcs.sbq.org.br as PDF file.
12. Narender, T.; Reddy, K. P.; Tetrahedron Lett. 2007, 48, 3177.
13. Varma, R. S.; Indian J. Chem., Sect. B: Org. Chem. Incl. Med.
Chem. 2006, 45, 2305.
Acknowledgements
14. van Santen, R. A.; Neurock, M.; Molecular Heterogeneous
Catalysis: A Conceptual and Computational Approach; Wiley-
VCH: Cambridge, 2006.
The authors are thankful to the SAP scheme (DRS-I)
from the University Grants Commission, DST (FIST &
PURSE), New Delhi. The authors are also thankful to the
Centre of Nanotechnology, Department ofApplied Physics,
University Sophisticated Instrument Facility (USIF),
AMU,Aligarh for providing powder X-ray diffractometer,
SEM-EDX facilities and SAIF, CDRI, Lucknow, Punjab
University, Chandigarh for providing spectral data. One
of the authors (T. K.) would like to acknowledge the
University Grant Commission (UGC), New Delhi, for
the financial assistance in the form of Senior Research
Fellowship [F. 17-43/08 (SA-I)].
15. Lancaster, M. In Handbook of Green Chemistry and Technology;
Clark, J. H.; Macquarrie, D. J., eds.; Blackwell:Abingdon, 2002.
16. Klemm, D.; Heublein, B.; Fink, H-P.; Bohn, A.; Angew Chem.,
Int. Ed. 2005, 44, 3358.
17. Mofakham, H.; Hezarkhani, Z.; Shaabani, A.; J. Mol. Catal. A:
Chem. 2012, 360, 26.
18. Kuarm, B. S.; Madhav, J. V.; Rajitha, B.; Reddy, Y. T.; Reddy,
P. N.; Crooks, P. A.; Synth. Commun. 2011, 41, 662.
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20. Safari, J.; Banitaba, S. H.; Khalili, S. D.; J. Mol. Catal. A: Chem.
2011, 335, 46.
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Submitted: December 18, 2013
Published online: April 11, 2014