Melamine trisulfunic acid: An efficient and recyclable solid acid catalyst for the synthesis of 4,4′-(arylmethylene)-bis-(1H-pyrazol-5-ols)

Article abstract of DOI:10.1002/jccs.201200345

Melamine trisulfunic acid is employed as a recyclable catalyst for the condensation reaction of aromatic aldehydes with 3-methyl-l-phenyl-2-pyrazolin- 5-one. This condensation reaction was performed in ethanol under refluxing conditions giving 4,4′-(arylm

Full text of DOI:10.1002/jccs.201200345

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Melamine Trisulfunic Acid: An Efficient and Recyclable Solid Acid Catalyst for the
Synthesis of 4,4¢-(Arylmethylene)-bis-(1H-pyrazol-5-ols)
Nasir Iravani,a* Jalal Albadi,b Hamide Momtazana and Mojtaba Baghernejadb
aDepartment of Chemistry, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran
bYoung Researchers Club, Gachsaran Branch, Islamic Azad University, Gachsaran, Iran
(Received: Jun. 11, 2012; Accepted: Oct. 2, 2012; Published Online: Dec. 20, 2012; DOI: 10.1002/jccs.201200345)
Melamine trisulfunic acid is employed as a recyclable catalyst for the condensation reaction of aromatic
aldehydes with 3-methyl-l-phenyl-2-pyrazolin-5-one. This condensation reaction was performed in etha-
nol under refluxing conditions giving 4,4¢-(arylmethylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols) in
80-96% yields.
Keywords: Melamine trisulfunic acid; Aldehydes; 3-Methyl-l-phenyl-2-pyrazolin-5-one;
4,4¢-(Arylmethylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols).
INTRODUCTION
Pyrazoles are an important class of bio-active drug
tial reflux with a further 24 h under ambient temperature to
go to completion.Wang et al,24 reported its synthesis in wa-
ter using sodium dodecyl sulfate as the surfactant catalyst
over a one-hour period, but the process needs a temperature
targets in the pharmaceutical industry, as they are the core
structure of numerous biologically active compounds.1-3
For example, they exhibit antianxiety, antipyretic, analge-
sic, and anti-inflammatory properties. 2,4-Dihydro-3H-
pyrazol-3-one derivatives including 4,4¢-(arylmethylene)-
bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols) have a broad
spectrum of approved biological activity, being used as
anti-inflammatory,4 antipyretic,5 gastric secretion stimu-
latory,6 antidepressant,7 antibacterial,8 andantifilarial
agents.9 Moreover, the corresponding 4,4¢-(arylmethyl-
ene)-bis-(1H-pyrazol-5-ols) are applied as fungicides,10
pesticides,11 insecticides,12 and dyestuffs,13-15 and as the
chelating and extracting reagents for different metal
ions.16,17 The conventional chemical approach to 4,4¢-
(arylmethylene)-bis-(3-methyl-1-phenyl-pyrazol-5-ols)
involves the successive Knoevenagel synthesis of the cor-
responding arylidene pyrazolones and its base-promoted
Michael reaction, and also one-pot tandem Knoevenagel-
Michael reaction of arylaldehydes with 2 equiv of 5-meth-
yl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one performed un-
der a variety of reaction conditions.18,19 The first set of pro-
cedures utilizes the catalysis of the components with
piperidine in ethanolic solution.20,21 The second set of
methods involve the non-catalyzed tandem Knoevenagel-
Michael reaction under neutral conditions in either etha-
nol22 or benzene23 solutions. Although it affords the corre-
sponding 4,4¢-(arylmethylene)-bis-(1H-pyrazol-5-ols) in
reliable 70-90% yields, the reaction requires 3-12 h of ini-
o
of 100 C. Finally, Elinson et al. utilized electrocatalytic
procedure for its synthesis.25 Further, Perumal and co-
workers reported the synthesis and antiviral activity of
4,4¢-(arylmethylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-
5-ols) using CAN as a catalyst,26 also Niknam and co-
worker reported the synthesis of these compounds using
silica-bonded S-sulfonic acid (SBSSA) and sulfuric acid
([3-(3-silicapropyl)sulfanyl]propyl) ester (SASPSPE) in
ethanol under refluxing conditions.27,28 However, most of
the methods suffer from at least one limitation that may in-
clude moderate yields, long reaction times, harsh reaction
conditions, or tedious workup procedures.
One of the efficient solid acid catalysts in organic
transformations is melamine trisulfunic acid (MTSA),29-34
(Scheme I) and in this article, we described a mild, efficient
and environmentally friendly method for the preparation of
4,4¢-(arylmethylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-
5-ol) derivatives in the presence of catalytic amounts of
melamine trisulfunic acid as catalyst.
Scheme I Preparation of Melamine trisulfunic acid
* Corresponding author. Tel.: +987423334751; Fax: +987423332003; Zip-Code: 75818-63876;
Nasir Iravani E-mail: iravani.nasir@yahoo.com, other E-mail: iravaninasir56@gmail.com
418
© 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2013, 60, 418-424

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Melamine Trisulfunic Acid
EXPERIMENTAL SECTION
(CH3), 33.60 (CH), 121.0 (C), 126.04 (CH), 126.38 (CH), 127.67
(CH), 128.61 (C), 129.40 (CH), 142.68 (C), 146.81 (C) ppm.
4,4¢-[(4-Methylphenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6b)
General
Aromatic aldehydes and 3-methyl-l-phenyl-2-pyrazolin-
5-one were obtained from Fluka and were used without further
purification. The IR spectra: Shimadzu IR-460 spectro meter; 1H
and 13C NMR spectra: Bruker DRX-400 AVANC instrument; in
DMSO-d6 at 400 MHz and 100 MHz, respectively, d in ppm, J in
Hz; Elemental analyses (C, H, and N) were performed with a
Heraeus CHN-O-Rapid analyzer. Melting points were determined
using a Melting Point SMP1 apparatus in open capillary tubes and
are uncorrected. All the products were characterized by compar-
ing their spectral (IR, 1H and 13C NMR), TLC, and physical data
with those reported in the literature27,28 and obtained results
showed that the analyses data were in agreement with the pro-
posed structures.
Yield: 0.38 g (85%), mp 203-205 oC (203 oC27). IR (KBr): n
= 3450 (OH), 3025 (CH arom), 2850 (CH aliph), 1598 (C=C),
1
1499 (C=C), 1410 (C=C), 1290 (C=N), 1022, 800, 745, 690. H
NMR: d = 2.26 (3H, s, CH3), 2.33 (6H, s, 2 CH3), 4.93 (1H, s, CH),
7.08 (2H, d, J = 8.0 Hz, 2CH), 7.15 (2H, d, J = 8.0 Hz, 2 CH), 7.25
(2H, t, J = 7.6 Hz, 2 CH), 7.45 (4H, t, J = 7.6 Hz, 4 CH), 7.72 (4H,
d, J = 7.6 Hz, 4 CH), 13.93 (2H, br.s, 2 OH). 13C NMR: d = 12.10
(CH3), 21.01 (CH3), 33.23 (CH), 120.95 (C), 126.02 (CH), 127.56
(CH), 129.17 (C), 129.40 (CH), 135.31 (CH), 139.55 (C), 146.78
(C) ppm.
4,4¢-[(4-Chlorophenyl)methylene)]-bis-(3-methyl-1-
Catalyst Preparation
phenyl-1H-pyrazol-5-ol) (6c)
A250-mL suction flask charged with chlorosulfonic acid (5
mL, 75.2 mmol) was equipped with a gas inlet tube for conducting
HCl gas over an adsorbing solution (i.e., water). Melamine (3.16
g, 25.07 mmol) was added in small portions over a period of 30
min at room temperature. HCl gas evolved from the reaction ves-
sel immediately. After completion of the addition of melamine,
the mixture was shaken for 30 min; meanwhile, the the residual
HCl was removed by suction. Melamine trisulfonic acid (7.9 g,
87%) was obtained as a white solid, which was stored in a capped
bottle.
Yield: 0.43 g (92%), mp 211-213 oC (210 oC27). IR (KBr): n
= 3400 (OH), 3050 (CH arom), 2900 (CH aliph), 1600 (C=C),
1590 (C=C), 1578 (C=C), 1498 (C=C), 1415 (C=C), 1280 (C=N),
808, 742, 685 cm-1 . 1H NMR: d = 2.34 (6H, s, 2 CH3), 4.99 (1H, s,
CH), 7.24-7.29 (4H, m, 4 CH), 7.35 (2H, d, J = 8.4 Hz, 2 CH),
7.46 (4H, t, J = 7.6 Hz, 4 CH), 7.72 (4H, d, J = 8 Hz, 4 CH), 13.89
(2H, br.s, 2 OH) ppm. 13C NMR: d = 12.07 (CH3), 33.02 (CH),
121.01 (C), 126.11 (CH), 128.50 (C), 129.41 (CH), 129.63 (CH),
131.06 (CH), 141.58 (C), 149.76 (C) ppm.
4,4¢-[(2-Chlorophenyl)methylene)]-bis-(3-methyl-1-
General Procedure for the Synthesis of 4,4¢-(aryl
methylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols)
A mixture of aromatic aldehyde (1 mmol), 5-methyl-2-
phenyl-2,4-dihydro-3H-pyrazol-3-one (2 mmol), and MTSA
(0.05 gr), in ethanol (10 mL) were added to a flask and heated un-
der reflux for an appropriate time. After completion of reaction,
as indicated by thin layer chromatography (TLC, silica gel SILG/
UV 254 plates), the reaction mixture was wash with warm ethanol
(3 × 30 mL). After cooling the crude products were precipitated.
The crude products were purified by recystallization from ethanol
(95%) and observed as white or yellow powders. The recovered
catalyst was washed with diethyl ether, dried, and reused in sub-
sequent runs.
phenyl-1H-pyrazol-5-ol) (6d)
o
o
Yield: 0.38 g (80%), mp 233-235 C (236-237 C27). IR
(KBr): n = 3450 (OH), 3060 (CH arom), 2905 (CH aliph), 1615
(C=C), 1595 (C=C), 1555 (C=C), 1496 (C=C), 1400 (C=C),
1350, 1295 (C=N), 836, 750, 690 cm-1. 1H NMR: d = 2.30 (6H, s,
2 CH3), 5.17 (1H, s, CH), 7.22-7.34 (4H, m, 4 CH), 7.40 (1H, d, J
= 7.82 Hz, CH), 7.44 (4H, t, J = 8.0 Hz, 4 CH), 7.71 (4H, d, J = 8.0
Hz, 4 CH), 7.81 (1H, d, J = 7.2 Hz, CH), 13.92 (2H, br.s, 2 OH)
ppm. 13C NMR: d = 12.33 (CH3), 32.14 (CH), 121.07 (C), 126.13
(CH), 127.4 (CH), 128.55 (C), 129.41 (CH), 129.95 (CH), 130.71
(CH), 132.4 (CH), 137.63 (CH), 139.89 (C), 146.54 (C) ppm.
4,4¢-[(2,4-Dichlorophenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6e)
o
o
4,4¢-(Phenylmethylene)-bis-(3-methyl-1-phenyl-1H-pyr-
Yield: 0.42 g (84%), mp 229-231 C (228-230 C27). IR
(KBr): n = 3480 (OH), 3050 (CH arom), 2900 (CH aliph), 1620
(C=C), 1590 (C=C), 1550 (C=C), 1499 (C=C), 1420 (C=C),
1380, 1290 (C=N), 850, 760, 680 cm-1.1H NMR: d = 2.33 (6H, s, 2
CH3), 5.22 (1H, s, CH), 7.11 (1H, d, J = 7.8 Hz, CH), 7.25 (1H, d,
J = 7.83 Hz, CH), 7.45 (2H, t, J = 7.72 Hz, 2 CH), 7.58 (4H, t, J =
7.76 Hz, 4 CH), 7.62 (4H, d, J = 7.75 Hz, 4 CH), 7.68 (1H, s, CH),
13.88 (2H, br.s, 2 OH) ppm. 13C NMR: d = 12.46 (CH3), 33.54
azol-5-ol) (6a)
o
o
Yield: 0.36 g (82%), mp 169-171 C (171-172 C.27). IR
(KBr): n = 3400 (OH), 3050 (CH arom), 2900 (CH aliph), 1598
(C=C), 1496 (C=C), 1403 (C=C), 1270 (C=N), 1020, 730, 690
cm-1. 1H NMR: d = 2.34 (6H, s, 2 CH3), 4.99 (1H, s, CH), 7.16-
7.32 (7H, m, 7CH ), 7.45 (4H, t, J = 7.6 Hz, 4 CH), 7.73 (4H, d, J =
8.0 Hz, 4 CH), 13.98 (2H, br.s, 2 OH) ppm. 13C NMR: d = 12.12
J. Chin. Chem. Soc. 2013, 60, 418-424
© 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
419

Article
Iravani et al.
(CH), 122.3 (C), 122.8 (CH), 126.54 (CH), 126.8 (CH), 128.76
(C), 129.85 (CH), 130.3 (CH), 131.8 (CH), 132.7 (C), 135.7 (C),
136.2 (C), 137.5 (C), 145.2 (C) ppm.
2 CH), 7.56 (4H, t, J = 7.67 Hz, 4 CH), 7.62 (2H, d, J = 7.31 Hz, 2
CH), 9.43 (1H, s, OH), 12.5 (1H, br.s, OH), 13.88 (1H, br.s, OH)
ppm. 13C NMR: d = 13.3 (CH3), 32.9 (CH), 112.9 (CH), 114.7
(CH), 121.3 (C), 121.6 (CH), 122.5 (CH), 126.2 (CH), 128.8 (C),
129.3 (CH), 130.0 (CH), 137.5 (C), 139.2 (C), 147.1(C), 156.7
(C) ppm.
4,4¢-[(4-Nitrophenyl)methylene)]-bis-(3-methyl-1-phen-
yl-1H-pyrazol-5-ol) (6f)
o
o
Yield: 0.46 g (96%), mp 225-227 C (224-226 C27). IR
(KBr): n = 3420 (OH), 3060 (CH arom), 2800 (CH aliph), 1598
(C=C), 1510 (C=C), 1490 (C=C), 1419 (C=C), 1400 (C=C), 1290
(C=N), 1342, 750, 690 cm-1. 1H NMR: d = 2.37 (6H, s, 2 CH3),
5.15 (1H, s, CH), 7.26 (2H, t, J = 7.6 Hz, 2 CH), 7.46 (4H, t, J =
8.0 Hz, 4 CH), 7.53 (2H, d, J = 8.4 Hz, 2 CH), 7.72 (4H, d, J = 8.0
Hz, 4 CH), 8.18 (2H, d, J = 8.8 Hz, 2 CH), 13.88 (2H, br.s, 2 OH)
ppm. 13C NMR: d = 12.06 (CH3), 33.65 (CH), 121.07 (C), 123.82
(CH), 126.2 (CH), 129.1 (C), 129.42 (CH), 137.64 (C), 146.4 (C),
146.79 (C), 151.79 (C) ppm.
4,4¢-[(3,4-Dimethoxyphenyl)methylene)]-bis-(3-methyl-
1-phenyl-1H-pyrazol-5-ol) (6j)
o
o
Yield: 0.40 g (81%), mp 194-196 C (195-197 C27). IR
(KBr): n = 3420 (OH), 3150 (CH arom), 3090 (CH arom), 2920
(CH aliph), 1590 (C=C), 1500 (C=C), 1420 (C=C), 1270 (C=N),
1120 (C-O), 745, 690 cm-1. 1H NMR: d = 2.29 (6H, s, 2 CH3), 3.63
(3H, s, OCH3), 3.67 (3H, s, OCH3), 4.86 (1H, s, CH), 6.78-6.83
(2H, m, 2 CH), 6.87 (1H, s, CH), 7.20 (2H, t, J = 6.8 Hz, 2 CH),
7.40 (4H, t, J = 7.4 Hz, 4 CH), 7.68 (4H, d, J = 7.8 Hz, 4 CH),
13.99 (1H, s, OH) ppm. 13C NMR: d =12.53 (CH3), 33.82 (CH),
56.39 (OCH3), 56.43 (OCH3), 112.56 (CH), 112.68 (CH), 120.20
(C), 121.46 (CH), 126.44 (CH), 129.78 (C), 135.85 (CH), 138.19
(C), 147.07 (C), 148.15 (C), 149.32 (C) ppm.
4,4¢-[(3-Nitrophenyl)methylene)]-bis-(3-methyl-1-phen-
yl-1H-pyrazol-5-ol) (6g)
o
o
Yield: 0.41 g (86%), mp 152-154 C (149-150 C27). IR
(KBr): n = 3400 (OH), 3050 (CH arom), 2915 (CH aliph), 1610
(C=C), 1590 (C=C), 1510 (C=C), 1498 (C=C), 1420 (C=C), 1345
(C=N), 760, 725, 690, 598 cm-1. 1H NMR: d = 2.37 (6H, s, 2 CH3),
5.17 (1H, s, CH), 7.27 (2H, t, J = 7.2 Hz, 2 CH), 7.46 (4H, t, J =
8.0 Hz, 4 CH), 7.62 (1H, t, J = 8.4 Hz, CH), 7.71-7.76 (5H, m, 5
CH), 8.09 (2H, d, J = 6.8 Hz, 2 CH), 13.89 (2H, br.s, 2 OH) ppm.
13C NMR: d = 12.09 (CH3), 33.31 (CH), 121.10 (C), 121.69 (CH),
122.23 (CH), 126.23 (CH), 129.45 (C), 130.18 (CH), 134.83
(CH), 145.06 (C), 146.82 (C), 148.24 (C) ppm.
4,4¢-[(4-Methylthiophenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6k)
o
o
Yield: 0.41 g (86%), mp 205-207 C (201-203 C27). IR
(KBr): n = 3440 (OH), 3055 (CH arom), 2900 (CH aliph), 1590
(C=C), 1500 (C=C), 1450(C=C), 1300 (C=N), 1040, 790, 750,
680 cm-1. 1H NMR: d = 2.52 (6H, s, 2 CH3), 2.53 (3H, s, CH3),
4.81 (1H, s, CH), 7.22 (2H, d, J = 7.92 Hz, 2 CH), 7.31 (2H, d, J =
7.81 Hz, 2 CH), 7.38 (2H, t, J = 7.1 Hz, 2 CH), 7.48 (4H, t, J = 7.5
Hz, 4 CH), 7.79 (4H, d, J = 7.72 Hz, 4 CH), 13.91 (2H, br.s, OH)
ppm.13C NMR: d = 12.62 (CH3), 21.54 (CH3), 34.24 (CH), 121.30
(C), 122.84 (CH), 122.09 (CH), 127.68 (CH), 128.98 (C), 129.33
(CH), 129.89 (CH), 134.39 (C), 134.85 (C), 137.54 (C), 138.65
(C), 145.84 (C) ppm.
4,4¢-[(4-Hydroxyphenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6h)
o
o
Yield: 0.38 g (84%), mp 153-155 C (152-153 C27). IR
(KBr): n = 3480 (OH), 3050 (CH arom), 2900 (CH aliph), 1595
(C=C), 1585 (C=C), 1450 (C=C), 1360, 1280 (C=N), 750, 690,
600, 595 cm-1. 1H NMR: d = 2.31 (6H, s, 2 CH3), 4.86 (1H, s, CH),
6.67 (2H, d, J = 8.7 Hz, 2 CH), 7.06 (2H, d, J = 8.5 Hz, 2 CH), 7.25
(2H, t, J = 7.33 Hz, 2 CH), 7.45 (4H, t, J = 7.83 Hz, 4 CH), 7.72
(4H, d, J = 7.98 Hz, 4 CH), 9.16 (1H, s, OH), 12.2 (1H, br.s, OH),
13.96 (1H, br.s, OH) ppm. 13C NMR: d =12.50 (CH3), 33.25 (CH),
115.73 (CH), 121.37 (C), 126.38 (CH), 128.96 (C), 129.77 (CH),
133.18 (CH), 147.04 (C), 156.37 (C) ppm.
4,4¢-[(4-Cyanophenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6l)
o
o
Yield: 0.43 g (93%), mp 206-208 C (210-212 C27). IR
(KBr): n = 3400 (OH), 3050 (CH arom), 2900 (CH aliph), 2210
(CN), 1595 (C=C), 1500 (C=C), 1458 (C=C), 1410, 1280 (C=N),
808, 748, 682 cm-1. 1H NMR: d = 2.36 (6H, s, 2 CH3), 5.09 (1H, s,
CH), 7.26 (2H, t, J = 7.2 Hz, 2 CH), 7.43-7.49 (6H, m, 6 CH),
7.73-7.79 (6H, m, 6 CH), 14.01 (1H, br.s, OH) ppm. 13C NMR: d =
12.10 (CH3), 33.81 (CH), 109.28 (C), 119.51 (C), 120.69 (C),
121.06 (CH) , 125.35 (CH), 126.12 (CH), 128.88 (C), 129.4 (CH),
132.58 (CH), 137.74 (C), 146.79 (C), 148.71(C) ppm.
4,4¢-[(3-Hydroxyphenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6i)
o
o
Yield: 0.40 g (88%), mp 169-170 C (165-168 C27). IR
(KBr): n = 3460 (OH), 3050 (CH arom), 2950 (CH aliph), 1599
(C=C), 1580 (C=C), 1455 (C=C), 1369, 1250 (C=N), 790, 680,
600, 590 cm-1. 1H NMR: d = 2.36 (6H, s, 2 CH3), 4.91 (1H, s, CH),
6.76 (1H, d, J = 8.21Hz, CH), 6.91 (1H, d, J = 8.26 Hz, CH), 6.97
(1H, s, CH), 7.16 (1H, t, J = 8.0 Hz, CH), 7.48 (2H, t, J = 7.46 Hz,
4,4¢-[(2-Hydroxyphenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6m)
o
o
Yield: 0.36 g (80%), mp 228-230 C (230-231 C28). IR
(KBr): n = 3400 (OH), 3050 (CH arom), 2900 (CH aliph), 1596
420
www.jccs.wiley-vch.de
© 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2013, 60, 418-424

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Melamine Trisulfunic Acid
(C=C), 1570 (C=C), 1498 (C=C), 1450 (C=C), 1366, 1280
(C=N), 750, 687 cm-1. 1H NMR: d = 2.32 (6H, s, 2 CH3), 5.21 (1H,
s, CH), 6.72-6.79 (2H, m, 2 CH), 6.99 (1H, t, J = 7.6 Hz, CH), 7.25
(2H, t, J = 7.2 Hz, 2 CH), 7.45 (4H, t, J = 7.6 Hz, 4 CH), 7.59 (1H,
d, J = 7.6 Hz, CH), 7.72 (4H, d, J = 8.0 Hz, 4 CH), 9.58 (1H, br.s,
OH), 12.33 (1H, br.s, OH), 14.39 (1H, br.s, OH) ppm. 13C NMR: d
= 12.24 (CH3), 27.77 (CH), 115.29 (CH), 119.08 (C), 121.08
(CH), 125.97 (C), 127.39 (CH), 129.27 (C), 129.38 (CH), 129.69
(CH), 146.81 (C), 154.35 (C) ppm.
72.09; H, 5.62; N, 12.01 (%). Found: C, 72.03; H, 5.45; N, 12.14
(%).
4,4¢-[(2-Bromophenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6q)
o
o
Yield: 0.44 g (86%), mp 201-204 C (198- 200 C28). IR
(KBr): n = 3450 (OH), 3050 (CH arom), 2900 (CH aliph), 1618
(C=C), 1596 (C=C), 1565 (C=C), 1550 (C=C), 1495 (C=C),
1395, 1365, 1310 (C=N), 1020, 900, 838, 790, 750, 690 cm-1. 1H
NMR: d = 2.31 (6H, s, 2 CH3), 5.12 (1H, s, CH), 7.15 (1H, t, J =
7.2 Hz, CH), 7.6 (2H, t, J = 7.2 Hz, 2 CH), 7.35 (1H, t, J = 7.6 Hz,
CH), 7.45 (4H, t, J = 7.6 Hz, 4 CH), 7.55 (1H, d, J = 8.0 Hz, CH),
7.71 (4H, d, J = 8.0 Hz, 4 CH), 7.83 (1H, m, CH), 12.58 (1H, br.s,
OH), 13.76 (1H, s, OH) ppm. 13C NMR: d =12.55 (CH3), 34.82
(CH), 121.03 (CH), 123.30 (CH), 126.06 (C), 127.92 (CH),
128.84 (C), 129.41 (CH), 131.01 (CH), 133.30 (CH), 141.48 (C),
146.53 (C) ppm.
4,4¢-[(4-Fluorophenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6n)
Yield: 0.43 g (94%), mp 180-182 oC (182 oC28). IR (KBr): n
= 3480 (OH), 3050 (CH arom), 2800 (CH aliph), 1600 (C=C),
1585 (C=C), 1498 (C=C), 1400 (C=C), 1370, 1318, 1219 (C=N),
1
1150 (C-F), 1020, 800, 790, 745, 680 cm-1. H NMR: d = 2.34
(6H, s, 2 CH3), 4.99 (1H, s, CH), 7.12 (2H, t, J = 8.8 Hz, 2 CH),
7.24-7.32 (4H, m, 4 CH), 7.45 (4H, t, J = 8.0 Hz, 4 CH), 7.73 (4H,
d, J = 8.0 Hz, 4 CH), 13.95 (1H, br.s, OH) ppm. 13C NMR: d =
12.09 (CH3), 32.92 (CH), 115.11 (CH), 115.32 (CH), 121.02
(CH), 126.08 (CH), 129.4 (C), 129.47 (CH), 129.55 (C), 138.65
(C), 146.71 (C), 159.95-162.36 (C-F, 1JCF = 241 Hz) ppm.
4,4¢-[(4-Isopropylphenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6o)
4,4¢-[(3-Bromophenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6r)
o
Yield: 0.45 g (88%), mp 164-166 C. IR (KBr): n = 3400
(OH), 3050 (CH arom), 2950-2800 (CH aliph), 1610 (C=C), 1595
(C=C), 1578 (C=C), 1563 (C=C), 1490, 1450, 1398, 1362, 1318,
1299 (C=N), 1000, 862, 790, 768, 755, 684 cm-1; 1H NMR: d =
2.35 (6H, s, 2 CH3), 5.02 (1H, s, CH), 7.24-7.32 (4H, m, 4 CH),
7.39-7.48 (6H, m, 6 CH), 7.73 (4H, d, J = 8.4 Hz, 4CH), 14.01
(1H, br.s, OH) ppm. 13C NMR: d = 12.10 (CH3), 33.37 (CH),
121.06 (C), 122.08 (CH), 126.13 (C), 126.96 (CH), 129.42 (C),
130.37 (CH), 130.81 (CH), 137.75 (CH), 145.67 (CH), 146.76
(C), 157.66 (C) ppm. Anal. Calcd for C27H23BrN4O2: C, 62.92; H,
4.50; N, 10.87 (%). Found: C, 62.64; H, 4.59; N, 10.78 (%).
o
o
Yield: 0.39 g (82%), mp 132-134 C (132-134 C28). IR
(KBr): n = 3400 (OH), 3090 (CH arom), 2950-2850 (CH aliph),
1610 (C=C), 1598 (C=C), 1578 (C=C), 1495 (C=C), 1419, 1410,
1370, 1358, 1280 (C=N), 1020, 780, 745, 682 cm-1. 1H NMR: d =
1.17 (6H, d, J = 6.8 Hz, 2 CH3), 2.36 (6H, s, 2 CH3), 2.83 (1H, sep,
J = 6.8 Hz, CH), 4.93 (1H, s, CH), 7.15 (2H, d, J = 8.0 Hz, 2 CH),
7.19-7.27 (4H, m, 4 CH), 7.45 (4H, t, J = 7.6 Hz, 4 CH), 7.74 (4H,
d, J = 8.0 Hz, 4 CH), 14.11 (1H, br.s, OH) ppm. 13C NMR: d =
12.14 (CH3), 24.40 (CH3), 33.32 (CH), 33.47 (CH), 118.81 (C),
120.96 (CH), 125.98 (CH), 126.54 (CH), 127.55 (C), 129.38
(CH), 137.92 (C), 140.21 (C), 146.33 (C), 146.77 (C) ppm.
4,4¢-[(4-Methoxyphenyl)methylene)]-bis-(3-methyl-1-
phenyl-1H-pyrazol-5-ol) (6p)
RESULTS AND DISCUSSION
The reaction of aromatic aldehydes with 2 equiva-
lents of 3-methyl-l-phenyl-2-pyrazolin-5-one in the pres-
ence of catalytic amounts of melamine trisulfunic acid in
ethanol under refluxing conditions produce 4,4¢-(arylmeth-
ylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols) in good
yields after purification (Scheme II).
o
Yield: 0.41 g (89%), mp 174-176 C. IR (KBr): n = 3450
(OH), 3050 (CH arom), 2800 (CH aliph), 1605 (C=C), 1598
(C=C), 1577 (C=C), 1505 (C=C), 1490 (C=C), 1385, 1245
(C=N), 1180, 1110, 1038, 870, 812, 785, 750, 690 cm-1. 1H NMR:
d = 2.33 (6H, s, 2 CH3), 3.71 (3H, s, OCH3), 4.92 (1H, s, CH), 6.85
(2H, d, J = 8.8 Hz, 2 CH), 7.19 (2H, d, J = 8.4 Hz, 2 CH), 7.25 (2H,
t, J = 7.2 Hz, 2 CH), 7.45 (4H, t, J = 7.6 Hz, 4 CH), 7.73 (4H, d, J =
8.0 Hz, 4 CH), 14.03 (1H, br.s, OH) ppm. 13C NMR: d = 12.13
(CH3), 32.87 (CH), 55.46 (OCH3), 113.98 (CH), 120.94 (C),
125.97 (C), 128.65 (C), 129.38 (CH), 134.61 (CH), 137.91 (CH),
146.68 (C), 157.99 (C) ppm. Anal. Calcd for C27H26N4O3: C,
Synthesis of 4,4¢-(arylmethylene)-bis-(3-
methyl-1-phenyl-1H-pyrazol-5-ol) deriva-
tives catalyzed by MTSA
Scheme II
J. Chin. Chem. Soc. 2013, 60, 418-424
© 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
421

Article
Iravani et al.
Table 1. Condensation reaction of p-nitrobenzaldehyde with 3-
methyl-l-phenyl-2-pyrazolin-5-one in the presence of
different amounts of catalysta
Table 2. Condensation reaction of p-chlorobenzaldehyde with 3-
methyl-l-phenyl-2-pyrazolin-5-one in the presence of
different catalystsa
Entry
Catalyst (mol %)
Time (min)
Yieldb (%)
Catalyst loading Time
Yieldb
Entry
Catalyst
(gr)
(min)
(%)27,28
1
2
3
4
5
6
No catalyst
30 h
30
< 10
85
5
1
MTSA
SBSSA
0.05
0.05
0.1
0.1
0.1
0.2
0.3
0.1
0.2
0.3
45
100
50
92
80
90
85
45
71
87
35
55
73
10
15
20
25
20
76
2
32
96
3
SBSSA
60
90
4
SASPSPE
Zeolite-HY
Zeolite-HY
Zeolite-HY
Amberlyst
Amberlyst
Amberlyst
132
120
120
120
120
120
120
120
87
5
6
a Reaction conditions: p-nitrobenzaldehyde (1 mmol), 3-methyl-l-
phenyl-2-pyrazolin-5-one (2 mmol), EtOH (10 mL), reflux
7
8
conditions.
b Isolated yield.
9
10
a Reaction conditions: p-chlorobenzaldehyde (1 mmol), 3-methyl-
l-phenyl-2-pyrazolin-5-one (2 mmol), EtOH (10 mL), reflux
To study the effect of catalyst loading and in order to
find optimum amount of the catalyst on the condensation
reaction of aromatic aldehydes with 3-methyl-l-phenyl-2-
pyrazolin-5-one, the reaction of p-nitrobenzaldehyde and
3-methyl-l-phenyl-2-pyrazolin-5-one was chosen as a
model reaction and different molar ratios of catalyst was
examined in the model reaction (Table 1). The obtained re-
sults clearly show that the best amount to prepare the prod-
ucts was achieved when 15 mol% of melamine trisulfunic
acid was used , and in absence of MTSA the condensation
conditions.
b Isolated yield.
reaction gaves very low yield after 30 h. Although 20 mol%
of MTSA accomplished this condensation, however, 15
mol% of MTSA per 1mmol of aldehyde was optimum in
terms of reaction time and isolated yield. Therefore, we
employed the optimized conditions (0.1 gmmol-1 of MTSA
in ethanol under refluxing conditions) for the condensation
Table 3. Synthesis of 4,4'-(arylmethylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols)
derivatives catalyzed by MTSA in ethanol under reflux conditionsa
Time
Entry
Ar (4)
Product (6)
Yieldb (%) m.p. (oC) Lit.m.p. (oC) 27,28
(min)
a
b
c
d
e
f
C6H5-
4-Me-C6H4-
4-Cl-C6H4-
6a
6b
6c
6d
6e
6f
100
56
82
85
92
80
84
96
86
84
88
81
86
93
80
94
82
89
86
88
169-171
203-205
211-213
233-235
229-231
225-227
152-154
153-155
169-170
194-196
205-207
206-208
228-230
180-182
132-134
174-176
201-204
164-166
171-172
203
45
210
2-Cl-C6H4-
70
236-237
228-230
224-226
149-150
152-153
165-168
195-197
201-203
210-212
230-231
182
2,4-(Cl)2-C6H3-
4-NO2-C6H4-
3-NO2-C6H4-
4-OH-C6H4-
3-OH-C6H4-
3,4-(MeO)2-C6H3-
4-MeS-C6H4-
4-CN-C6H4-
2-OH-C6H4-
4-F-C6H4-
180
32
g
h
i
6g
6h
6i
60
80
135
90
j
6j
k
l
6k
6l
35
55
m
n
o
p
q
r
6m
6n
6o
6p
6q
6r
110
20
4-iPr-C6H4-
60
132-134
-
4-MeO-C6H4-
2-Br-C6H4-
50
90
198-200
-
3-Br-C6H4-
100
a Reaction conditions: aromatic aldehyde (1 mmol), 3-methyl-l-phenyl-2-pyrazolin-5-one (2
mmol), EtOH (10 mL), reflux conditions.
b Isolated yield.
422
www.jccs.wiley-vch.de
© 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2013, 60, 418-424

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Melamine Trisulfunic Acid
reaction of various aryl aldehydes with 3-methyl-l-phen-
yl-2-pyrazolin-5-one into the corresponding 4,4¢-(aryl-
methylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols)
(Scheme II).
any additional treatment (Fig. 1).
CONCLUSIONS
In conclusion, we have prepared some 4,4¢-(aryl-
methylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols) by
a tandem condensation reaction of aromatic aldehydes with
2 equiv of 3-methyl-l-phenyl-2-pyrazolin-5-one in the
presence of melamine trisulfunic acid in refluxing ethanol.
This catalyst synthetic method seems facile, good yields,
workup procedure is easy and gives pure target compounds
containing several potential centers for further modifica-
tion.
Herein, as sample, the results of the presented proto-
col in comparison with the different available solid acids
such as SBSSA, amberlyst and zeolite-HY in condensation
reaction of p-chlorobenzaldehyde with 3-methyl-l-phenyl-
2-pyrazolin-5-one are shown in Table 2. The information
of this table show that MTSA presented better result in
comparison with the other solid acids in this condensation
reaction and probably, this is due to existing of three acidu-
lous function in the structure of MTSA.
The results of this synthetic method is presented in
Table 3. As shown in this table, all aromatic aldehydes re-
acted with 3-methyl-l-phenyl-2-pyrazolin-5-one to afford
4,4¢-(arylmethylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-
5-ols) in excellent yields. On the other hand, benzalde-
hydes with electrondonating or electron-withdrawing groups,
that is, 3,4-dimethoxybenzaldehyde 4j or 4-nitrobenzalde-
hyde 4f, were condensed into the corresponding 4,4¢-(aryl-
methylene)-bis-(3-methyl-1-phenyl-1H-pyrazol-5-ols) 6j
and 6f in high yields.
ACKNOWLEDGEMENTS
We are thankful to the Gachsaran branch, Islamic
Azad University, for the partial support of this work.
REFERENCES
1. McDonald, E.; Jones, K.; Brough, P. A.; Drysdale, M. J.;
Workman, P. Curr. Top. Med. Chem. 2006, 6, 1193-1203.
2. Elguero, J. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.; Oxford:
Pergamon, 1996; Vol. 5.
3. Elguero, J.; Goya, P.; Jagerovic, N.; Silva, A. M. S. Targets
Heterocycl. Syst. 2002, 6, 52-98.
The reusability of catalyst is important for the large
scale operation and industrial point of view. Therefore, the
possibility of recycling the catalyst was examined using the
reaction of p-nitrobenzaldehyde and 3-methyl-l-phenyl-2-
pyrazolin-5-one under the optimized conditions. Upon
completion, the reaction mixture was washed with warm
ethanol (3 × 30 mL). The recovered catalyst was washed
with diethyl ether, dried, and reused for subsequent runs.34
The recycled catalyst could be reused five times without
4. Sugiura, S.; Ohno, S.; Ohtani, O.; Izumi, K.; Kitamikado, T.;
Asai, H.; Kato, K. J. Med. Chem. 1977, 20, 80-85.
5. Behr, L. C.; Fusco, R.; Jarboe, C. H. In The Chemistry of
Heterocyclic Compounds: Pyrazoles, Pyrazolines, Pyrazoli-
dines, Indazoles and Condensed Rings; Weissberger, A., Ed.;
Interscience: New York, 1967.
6. Rosiere, C. E.; Grossman, M. I. Science, 1951, 113, 651.
7. Bailey, D. M.; Hansen, P. E.; Hlavac, A. G.; Baizman, E. R.;
Pearl, J.; Defelice, A. F.; Feigenson, M. E. J. Med. Chem.
1985, 28, 256-260.
8. Mahajan, R. N.; Havaldar, F. H.; Fernandes, P. S. J. Indian
Chem. Soc. 1991, 68, 245-246.
9. Chauhan, P. M. S.; Singh, S.; Chatterjee, R. K. Indian. J.
Chem., Sect. B. 1993, 32, 858-861.
10. Singh, D.; Singh, D. J. Indian Chem. Soc. 1991, 68, 165-167.
11. Londershausen, M. Pestic. Sci. 1996, 48, 269-292.
12. Lubs, H. A. The Chemistry of Synthetic Dyes and Pigments;
American Chemical Society: Washington, DC, 1970.
13. Uzoukwu, A. B. Polyhedron. 1993, 12, 2719-2724.
14. Maurya, R. C.; Verma, R. Indian J. Chem., Sect. A 1997, 36,
596-598.
15. Garnovskii, A. D.; Uraev, A. I.; Minkin, V. I. Arkivoc 2004,
iii, 29-41.
Fig. 1. Recyclability of MTSA (15 mol %, 0.05 gr) in
the reaction of p-nitrobenzaldehyde (1 mmol)
and 3-methyl-l-phenyl-2-pyrazolin-5-one (2
mmol) in EtOH under refluxing conditions. Se-
ries 1: Yield (%), Series 2: Time (min).
16. Sridhar, R.; Perumal, P. T.; Etti, S.; Shanmugam, G.;
Ponnusamy, M. N.; Prabavathy, V. R.; Mathivanan, N.
Bioorg. Med. Chem. Lett. 2004, 14, 6035-6040.
J. Chin. Chem. Soc. 2013, 60, 418-424
© 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
423

Article
Iravani et al.
17. Sivaprasad, G.; Perumal, P. T.; Prabavathy, V. R.; Mathivanan,
N. Bioorg. Med. Chem. Lett. 2006, 16, 6302-6305.
2009, 19, 4501-4503.
27. Niknam, Kh.; Saberi, D.; Sadeghian, M.; Deris, A, Tetra-
hedton Lett. 2010, 51, 692-694.
18. Hamama, W. S. Synth. Commun. 2001, 31, 1335-1345.
19. Li, X.-L.; Wang, Y.-M.; Tian, B.; Matsuura, T.; Meng, J.-B.
J. Heterocycl. Chem. 1998, 35, 129-134.
28. Tayebi, Sh.; Baghernejad, M.; Saberi, D.; Niknam, Kh. Chin.
J. Catal. 2011, 32, 1477-1483.
20. Singh, D.; Singh, D. J. Chem. Eng. Data. 1984, 29, 355-356.
21. Mitra, A. S.; Rout, M. K. J. Indian Chem. Soc. 1961, 38, 893.
22. Pavlov, P. T.; Goleneva, A. F.; Lesnov, A. E.; Prokhorova, T.
S Pharm. Chem. J. (Engl. Trans.) 1998, 32, 370-372.
23. Buzykin, B. I.; Lonshchakova, T. I. Bull. Acad. Sci. USSR,
Div. Chem. Sci. (Engl. Trans.) 1971, 2224-2226.
29. Shirini, F.; Zolfigol, M. A.; Albadi, J. Synth. Commun. 2010,
40, 910-914.
30. Shirini, F.; Zolfigol, M. A.; Aliakbar, A. R.; Albadi, J. Synth.
Commun. 2010, 40, 1022-1028.
31. Shirini, F.; Albadi, J. Bull. Korean Chem. Soc. 2010, 31,
1119-1120.
24. Wang, W.; Wang, S.-X.; Qin, X.-Y.; Li, J.-T. Synth. Commun.
2005, 35, 1263-1269.
32. Shirini, F.; Zolfigol, M. A.; Albadi, J. J. Iran. Chem, Soc.
2010, 7, 895-899.
25. Elinson, M. N.; Dorofeev, A. S.; Nasybullin, R. F.; Nikishin,
G. I. Synthesis. 2008, 12, 1933-1937.
33. Shirini, F.; Zolfigol, M. A.; Albadi, J. Chin. Chem. Lett.
2011, 22, 318-321.
26. Sujatha, K.; Shanthi, G.; Selvam, N. P.; Manoharan, S.;
Perumal, P. T.; Rajendran, M. Bioorg. Med. Chem. Lett.
34. Ma, W.; Wang, X.; Yan, F.; Wu, L.; Wang, Y. Monatsh.
Chem. 2011, 142, 163-167.
424
www.jccs.wiley-vch.de
© 2013 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2013, 60, 418-424