1,3,5-tris(hydrogensulfato) benzene: A new and efficient catalyst for synthesis of 4,4′-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives

Article abstract of DOI:10.1016/S1872-2067(11)60477-4

1,3,5-Tris(hydrogensulfato) benzene (THSB) was easily prepared by the reaction between phloroglucinol and chlorosulfonic acid in dichloromethane at room temperature. This compound was then used as an efficient catalyst for the synthesis of 4,4′-(arylmethy

Full text of DOI:10.1016/S1872-2067(11)60477-4

CHINESE JOURNAL OF CATALYSIS
Volume 33, Issue 12, 2012
Online English edition of the Chinese language journal
Cite this article as: Chin. J. Catal., 2012, 33: 1945–1949.
ARTICLE
1,3,5-Tris(hydrogensulfato) Benzene: A New and Efficient
Catalyst for Synthesis of
4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) Derivatives
Zahed KARIMI-JABERI*, Baharak POOLADIAN, Masoud MORADI, Ehsan GHASEMI
Department of Chemistry, Firoozabad Branch, Islamic Azad University, P.O. Box 74715-117 Firoozabad, Fars, Iran
Abstract: 1,3,5-Tris(hydrogensulfato) benzene (THSB) was easily prepared by the reaction between phloroglucinol and chlorosulfonic
acid in dichloromethane at room temperature. This compound was then used as an efficient catalyst for the synthesis of
4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) through the condensation reactions of 1-phenyl-3-methylpyrazol-5-one with several different
aromatic aldehydes in ethanol at 75 °C. The present methodology offers several advantages over existing methodologies, such as excellent
yields, simple procedure, easy work-up and ecofriendly reaction conditions.
Key words: 1,3,5-tris(hydrogensulfato) benzene; aromatic aldehydes; 1-phenyl-3-methylpyrazol-5-one; 4,4'-(arylmethylene)bis
(1H-pyrazol-5-ols); ethanol; multicomponent reaction
Heterocycles represent the largest of the classical divisions
in organic chemistry by far and are of immense importance
both biologically and industrially. Pyrazoles are an important
class of heterocyclic compound. Examination of the chemical
literature reveals that a great many synthetic pyrazole deriva-
tives have been reported, with applications across a wide range
of fields, where they have been used as pharmaceuticals, ag-
rochemicals, and photographic agents. 2,4-Dihydro-3H-
pyrazol-3-one derivatives, including the 4,4'-(arylmethylene)
bis(1H-pyrazol-5-ols) have a broad spectrum of approved
biological activity, and have been used as anti-inflammatory
[1], antipyretic [2], gastric secretion stimulatory [3], antide-
pressant [4], antibacterial [5], antiviral [6], and antifilarial
agents [7]. They have also used as fungicides [8], insecticides
[9], and dyestuffs [1013].
Over the years, multicomponent reactions [1416] (MCRs)
have become increasingly popular as tools for enabling the
introduction of sufficient molecular diversity and complexity.
These reactions have gained significant popularity in recent
years because of their atom-economy and straightforward
reaction design, which also allows for substantial minimization
in the levels of waste generated from the process with consid-
erable saving in labor, time, and costs [1719]. MCRs leading
to the generation of interesting heterocyclic scaffolds are par-
ticularly useful for the construction of diverse chemical li-
braries of ‘drug like’ molecules.
Recently, several different three component one-pot con-
densation reactions have been reported between
1-phenyl-3-methylpyrazol-5-one and a variety of different
aldehydes for the construction of 4,4'-(arylmethylene)bis
(1H-pyrazol-5-ol) derivatives [6, 2032]. Several different
catalysts have been reported to promote this reaction, including
ceric ammonium nitrate (CAN) [6], sodium dodecyl sulfate
(SDS) as a surfactant catalyst [20], ETBA [21], NaBr [22],
[Cu(3,4-tmtppa)](MeSO4)4 [23], silica-bonded S-sulfonic acid
(SBSSA) [24], silica sulfuric acid (SSA) [25], H2O [26], sul-
furic acid ([3-(3-silicapropyl)sulfanyl] propyl)ester (SASPSPE)
[27], xanthan sulfuric acid [28], PEG-SO3H [29], ionic liquid
[HMIM]HSO4 [30], 3-minopropylated silica gel (AP-SiO2)
[31], and phosphomolybdic acid [32].
Although some of these methods afford moderate to high
yields of the corresponding products, the majority suffer from
one or more of the following disadvantages, including (1) the
use of a costly catalyst; (2) the requirement for a tedious
work-up procedure; (3) the need for high temperatures; and (4)
long reaction times. Herein, we report the development of a
Received 30 July 2012. Accepted 9 October 2012.
*Corresponding author. Tel: +98-917-107-6935; Fax: +98-712-6224402; E-mail: zahed.karimi@yahoo.com
Copyright © 2012, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(11)60477-4

Zahed KARIMI-JABERI et al. / Chinese Journal of Catalysis, 2012, 33: 1945–1949
OSO3H
OH
CH2Cl2 , RT
+ 3HCl (g)
+ ClSO3H (3 eq)
HO3SO
OSO3H
HO
OH
THSB
Scheme 1. Preparation of THSB.
mild, efficient, and environmentally benign procedure for the
synthesis of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) deri-
vates from the condensation reaction of aldehydes and
1-phenyl-3-methylpyrazol-5-one in the presence of
1,3,5-tris(hydrogensulfato) benzene (THSB) as an efficient and
new catalyst.
completion of the addition, the mixture was shaken for 3 h, and
the residual HCl was removed by suction. The solid residue
was washed with n-hexane (10 ml) and filtered to give the
desired product as a yellow solid material in 95% yield.
1.3 General procedure for the one-pot synthesis of
4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives
1 Experimental
THSB (0.04 mmol, 0.014 g) and silica gel (0.006 g) were
added to a solution of aromatic aldehyde 1 (1 mmol, Scheme 2)
and 1-phenyl-3-methylpyrazol-5-one 2 (2 mmol, scheme 2) in
ethanol (2 ml), and the resulting mixture was stirred at 75 °C
for the specified period of time, as indicated in Table 1. Upon
completion of the reaction, as confirmed by TLC, the reaction
mixture was cooled to room temperature. The resulting pre-
cipitated product was then filtered and washed with n-hexane
(10 ml) to afford the pure product 3 (3a–3u) as a white powder.
1.1 General
All of the chemicals were purchased from Merck and Al-
drich. Melting points were determined in open capillary tubes
and are uncorrected. IR measurements were carried out using
KBr pellets on a Fourier transform infrared (FT-IR) spec-
1
trometer (Manufacturer, City, State/Country). H (250 MHz)
and 13C (62.5 MHz) NMR spectra were recorded on a Bruker
Avance 250 spectrometer (Bruker, City, State/Country) in
DMSO-d6 using tetramethylsilane (TMS) as an internal refer-
ence. All of the products have been reported previously in the
literature and were characterized according to their spectral and
physical data. Reaction monitoring for the progress of all of the
reactions was carried out by thin-layer chromatography (TLC)
using silica gel 60 GF245 precoated sheets and were visualized
using a UV-lamp at a wave length of 254 nm. All chemicals and
solvents were of reagent grade and the latter were distilled and
dried before use. The elemental analyses were performed with
an Elementar Analysensysteme GmbH VarioEL in CHNS
mode.
1.4 Characterization of some representative compounds
THSB. Pale yellow solid. IR (KBr, cm–1): 3403, 1284, 1174,
578. 1H NMR (250 MHz, DMSO-d6): 5.82 (s, 3H, ArH). Anal.
Calcd For C6H6O12S3: C, 19.67; H, 1.65; S, 26.26; Found: C,
19.57; H, 1.59; S, 26.19.
4,4'-[(4-Chloro-3-nitrophenyl)methylene]bis(3-methyl-1-ph
enyl-1H-pyrazol-5-ol) (Table 1, Entry 10, 3j). Pale yellow solid.
IR (KBr, cm1): 3425, 3054, 2923, 1598, 1570, 1530, 1501,
1368, 750. 1H NMR (250 MHz, DMSO-d6): 2.32 (s, 6H, 2CH3),
5.80 (s, 1H, CH), 7.23 (d, 2H, J = 2.5 Hz, ArH), 7.25 (d, 4H, J =
2.5 Hz, ArH), 7.547.57 (m, 1H, ArH), 7.657.66 (m, 5H,
ArH), 7.84 (s, 1H, ArH); 13C NMR (62.5 MHz, DMSO-d6):
11.9, 104.1, 121.1, 122.9, 124.6, 126.2, 129.1, 129.4, 131.7,
133.3, 137.4, 144.0, 146.7, 147.8. Anal. Calcd For
C27H22ClN5O4: C, 62.85; H, 4.30; N, 13.57; Found: C, 62.74; H,
4.25; N, 13.50.
1.2 Preparation of THSB
A solution of chlorosulfonic acid (8.74 g, ca. 5 ml, 75 mmol)
in CH2Cl2 (20 ml) was added to phloroglucinol (3.15 g, 25
mmol) in a drop-wise manner over a period of 1 h at room
temperature (Scheme 1). HCl evolved immediately. Upon
4,4'-[(2-Methoxyphenyl)methylene]bis(3-methyl-1-phenyl-
Me
N
Ar
Me
N
N
Ph
Me
THSB
EtOH, 75 C
+
ArCHO
N
o
O
N
N
1
OH HO
Ph
Ph
2
3a-3u
85%-98%
21 examples
Scheme 2. Synthesis of the 4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives catalyzed by THSB.

Zahed KARIMI-JABERI et al. / Chinese Journal of Catalysis, 2012, 33: 1945–1949
1H-pyrazol-5-ol) (Table 1, Entry 14, 3n). Yellow solid. IR
ately evolved from the reaction mixture. Furthermore, the
catalyst itself was safe and easy to handle (Scheme 1).
In connection with our ongoing work towards the devel-
opment of new synthetic routes for the construction of complex
heterocyclic compounds, such as the newly discovered
2-amino-4H-pyran-3-carbonitriles [33], 2,3-dihydro quina-
zolin-4(1H)-ones [34], tetrahydrobenzo[a]xanthen-11-ones
[35], and dihydropyrano[2,3-c]pyrazoles [36], herein we report
the three-component condensation reaction of aromatic alde-
hydes 1 with 1-phenyl-3-methylpyrazol-5-one 2 in ethanol in
the presence of THSB as a novel catalyst with a reaction time
of 2–5 min, allowing for the one-pot formation of
4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) 3 in excellent yields
(Scheme 2).
(KBr, cm1): 3427, 3062, 2922, 1598, 1575, 1497, 1241, 756.
1H NMR (250 MHz, DMSO-d6): 2.26 (s, 6H, 2CH3), 3.79 (s,
3H, OCH3), 5.18 (s, 1H, CH), 6.826.93 (m, 2H, ArH),
7.117.24 (m, 3H, ArH), 7.41 (t, 4H, J = 7 Hz, ArH), 7.60 (d,
1H, J = 7.5 Hz, ArH), 7.677.70 (m, 4H, ArH); 13C NMR (62.5
MHz, DMSO-d6): 12.0, 27.8, 55.9, 111.2, 120.4, 121.0, 125.9,
127.7, 128.9, 129.3, 130.5, 130.7, 130.9, 131.1, 146.6, 156.2.
Anal. Calcd For C28H26N4O3 : C, 72.09; H, 5.62; N, 12.01;
Found: C, 71.98; H, 5.57; N, 11.93.
1,4-Diphenylene-4,4'-(methylene)bis(3-methyl-1-phenyl-1
H-pyrazol-5-ol) (Table 2, 3u). White cream solid. IR (KBr,
cm–1): 3415, 3026, 1590, 1495, 1410, 1350, 1290, 1120, 1020,
1
860, 745, 690. H NMR (250 MHz, DMSO-d6): 2.28 (s, 12H,
CH3), 5.07 (s, 2H, CH), 7.17 (s, 4H, CH), 7.23 (t, 4H, J = 7.1
Hz, Ar), 7.41 (t, 8H, J = 7.8 Hz, Ar), 7.69 (d, 8H, J = 7.9 Hz,
Ar), 12.43 (br, 2H, OH) 14.10 (2H, s, OH); 13C NMR
(62.5MHz, DMSO-d6): 12.6, 33.6, 121.5, 128.0, 129.7, 140.9,
147.0, 155.0. Anal. Calcd for C48H42N8O4: C, 72.52; H, 5.32;
N, 14.09; Found: C, 72.35; H, 5.29; N, 13.85.
For the initial optimization of the reaction conditions, the
condensation reaction of 4-chlorobenzaldehyde with
1-phenyl-3-methylpyrazol-5-one was investigated in ethanol as
a model reaction. The best result was achieved when
4-chlorobenzaldehyde was reacted with 1-phenyl-3-
methylpyrazol-5-one (in a 1:2 molar ratio) in the presence of
THSB (X wt%) at 75 °C for 2 min (Table 1, entry 2).
2 Results and discussion
These conditions were therefore selected as the optimized
conditions and employed for the condensation reaction of a
variety of different aryl aldehydes with 3-methyl-l-phenyl-5-
pyrazolone to give the corresponding 4,4'-(arylmethylene)
bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) derivatives. The re-
sults are summarized in Table 1.
1,3,5-Tris(hydrogensulfato) benzene (THSB) was easily
prepared by the addition of chlorosulfonic acid to phloroglu-
cinol (1,3,5-benzenetriol) at room temperature. This reaction
proceeded smoothly and cleanly, with HCl gas being immedi-
Table 1 Synthesis of 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols)
Melting point (°C)
Entry
Ar
Product
Time (min)
Isolated yield (%)
This work
Reported
1
2
C6H5
4-ClC6H4
3a
3b
3c
3d
3e
3f
5
2
2
3
3
3
3
4
3
2
3
4
3
5
5
3
3
3
3
3
5
93
95
95
98
90
98
96
95
98
95
92
90
90
90
90
98
95
95
95
90
85
169171
215216
235237
183185
182184
212214
225
170172 [25]
215217 [25]
235237 [25]
183185 [26]
182184 [32]
210212 [25]
224226 [32]
152154 [32]
227229 [24]
—
3
2-ClC6H4
4
4-BrC6H4
5
4-FC6H4
6
4-CNC6H4
4-NO2C6H4
3-NO2C6H4
2,4-Cl2C6H3
4-Cl-3-NO2C6H3
4-CH3C6H4
3-CH3C6H4
4-OCH3C6H4
2-OCH3C6H4
4-OHC6H4
2-pyridyl–
3-pyridyl–
2-naphthyl–
2-furyl–
7
3g
3h
3i
8
151154
227229
237238
201203
238241
176179
211214
154157
229231
239240
204206
188191
211212
209212
9
10
11
12
13
14
15
16
17
18
19
20
21
3j
3k
3l
202204 [25]
242243 [28]
176178 [32]
210213 [30]
155157 [24]
232233 [6]
238240 [25]
206208 [25]
188190 [32]
213214 [32]
214216 [27]
3m
3n
3o
3p
3q
3r
3s
(CH3)2CH
CHOC6H4
3t
3u
Reaction conditions: aromatic aldehyde (1 mmol), 1-phenyl-3-methylpyrazol-5-one (2 mmol), THSB (0.014 g), 75 °C, EtOH (2 ml).
aReaction conditions: terephthaldehyde (1 mmol), 1-phenyl-3-methylpyrazol-5-one (4 mmol), THSB (0.014 g), 75 °C, EtOH (2 ml).

Zahed KARIMI-JABERI et al. / Chinese Journal of Catalysis, 2012, 33: 1945–1949
Table 2 Comparison of the results obtained using THSB with other catalyst for the synthesis of the 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols)
Entry
Reagent and conditions
CAN (5 mol%), H2O, RT
Time (min)
1025
Yield (%)
8894
8090
7893
7284
7590
7695
7694
4092
9098
9196
9098
Ref
[6]
1
2
SBSSA (0.1 g), EtOH (10 ml), reflux
SSA (0.08 g), EtOH:H2O (10 ml), 70 °C
—, H2O (20 ml), Reflux
40240
20150
360480
120240
1530
[24]
3
[25]
4
[26]
5
SASPSPE (0.1 g), EtOH (10 ml), reflux
xanthan sulfuric acid (0.08 g), EtOH (5 ml), reflux
PEG-SO3H (1.5 mol%), H2O, Reflux
[HMIM]HSO4 (10 mol%), EtOH, RT
AP-SiO2 (3.22 g), CH3CN (10 ml), RT
phosphomolybdic acid (10 mol%), EtOH (5 ml), RT
THSB (0.014 g), EtOH (2 ml), 75°C
[27]
6
[28]
7
15120
2075
[29]
8
[30]
9
545
[31]
10
11
210330
25
[32]
present method
As shown in Table 1, all of the aromatic aldehydes 1 reacted
successfully with 1-phenyl-3-methylpyrazol-5-one 2 in the
presence of THSB in ethanol at 75 °C, to afford the corre-
sponding products 3 in excellent yields. Aromatic aldehydes
containing electron-withdrawing (e.g., nitro and halide groups)
and electron-donating groups (e.g., hydroxyl and alkoxy
groups) were employed and reacted well to give the corre-
sponding products 3 in excellent yields under these reaction
conditions, leading to the conclusion that the electronic nature
of the substituents on the aromatic ring had no discernible
impact on the course of the reaction.
procedure. We are currently exploring further applications of
the THSB catalyst to other organic reactions in our laboratory.
References
1
2
Sugiura S, Ohno S, Ohtani O, Izumi K, Kitamikado T, Asai H,
Kato K, Hori M, Fujimura H. J Med Chem, 1977, 20: 80
Behr L C, Fusco R, Jarboe C H. In: Weissberger A ed. The
Chemistry of Heterocyclic Compounds, Pyrazoles, Pyrazolines,
Pyrazolidines, Indazoles, and Condensed Rings. New York:
Interscience, 1967. 22
3
4
Rosiere C E, Grossman M I. Science, 1951, 113: 651
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
Mahajan R N, Havaldar F H, Fernandes P S. J Indian Chem
Soc, 1991, 68: 245
The practicality and synthetic efficiency of this reaction was
highlighted by the reaction of terephthaldehyde with
1-phenyl-3-methylpyrazol-5-one to give structurally complex
di(bis-pyrazol-5-ol) Table 1 [25,27].
5
6
7
Sujatha K, Shanthi G, Selvam N P, Manoharan S, Perumal P T,
Rajendran M. Bioorg Med Chem Lett, 2009, 19: 4501
Chauhan P M S, Singh S, Chatterjee R K. Indian J Chem Sect
B, 1993, 32: 858
To highlight the advantages of the THSB catalyst over the
other catalysts reported in the literature, the results obtained
using this catalyst were compared with those obtained from
other catalysts for the synthesis of 4,4'-(arylmethylene)
bis(1H-pyrazol-5-ols). From Table 2, it is clear that THSB
appeared to promote the reaction more effectively than a
number of other catalysts, particularly in terms of the time
required to complete the reaction and the reaction yield. This
method offers some advantages in terms of very fast reaction
times, simplicity of performance, low cost, and it follows
along the line of green chemistry.
8
9
Singh D, Singh D. J Indian Chem Soc, 1991, 68: 165
Lubs H A. The Chemistry of Synthetic Dyes and Pigments.
Washington DC: American Chemical Society, 1970.
10 Uzoukwu A B, Al-Juaid S S, Hitchcock P B, Smith J D. Poly-
hedron, 1993, 12: 2719
11 Maurya R C, Verma R. Indian J Chem Sect A, 1997, 36: 596
12 Garnovskii A D, Uraev A I, Minkin V I. Arkivoc, 2004, (3): 29
13 Pettinari C, Marchetti F, Pettinari R, Drozdov A, Troyanov S,
Voloshin A I, Shavaleen N M. J Chem Soc Dalton Trans, 2002,
1409
3 Conclusions
14 Cariou C C A, Clarkson G J, Shipman M. J Org Chem, 2008,
73: 9762
In conclusion, we have described the development of an ef-
ficient one-pot three-component condensation reaction of
aromatic aldehydes with 1-phenyl-3-methylpyrazol-5-one in
15 Candeias N R, Montalbano F, Cal P M S D, Gois P M P. Chem
Rev, 2010, 110: 6169
16 Banfi L, Basso A, Giardini L, Riva R, Rocca V, Guanti G. Eur
J Org Chem, 2011: 100
ethanol
for
the
synthesis
of
4,4'-(arylmethylene)bis(1H-pyrazol-5-ol) derivatives, with the
process being catalyzed by 1,3,5-tris(hydrogensulfato) benzene
(THSB) as a novel catalyst. This new method has the advan-
tages of higher yields, mild reaction conditions, shorter reac-
tion times, and is a convenient and environmental friendly
17 Basso A, Banfi L, Riva R, Guanti G. J Org Chem, 2005, 70:
575
18 Yue T, Wang M X, Wang D X, Masson G, Zhu J P. J Org Chem,
2009, 74: 8396
19 Trofimov B A, Andriyankova L V, Belyaeva K V, Malkina A G,
Nikitina L P, Afonin A V, Ushakov I A. Eur J Org Chem, 2010:

Zahed KARIMI-JABERI et al. / Chinese Journal of Catalysis, 2012, 33: 1945–1949
1772
28 Suresh Kuarm B, Rajitha B. Synth Commun, 2012, 42: 2382
29 Hasaninejad A, Shekouhy M, Zare A, Ghattali S M S H, Gol-
zara N. J Iran Chem Soc, 2011, 8: 411
20 Wang W, Wang S X, Qin X Y, Li J T. Synth Commun, 2005, 35:
1263
21 Shi D Q, Chen J, Wu N, Zhuang Q Y, Wang X S. Chin J Org
Chem, 2005, 25: 405
30 Zang H J, Su Q H, Mo Y M, Cheng B. Ultrason Sonochem,
2011, 18: 68
22 Elinson M N, Dorofeev A S, Nasybullin R F, Nikishin G I.
Synthesis, 2008: 1933
31 Sobhani S, Hasaninejad A R, Faal Maleki M, Pakdin Parizi Z.
Synth Commun, 2012, 42: 2245
23 Sobhani S, Safaei E, Hasaninejad A R, Rezazadeh S. J
Organomet Chem, 2009: 694: 3027
32 Phatangare K R, Padalkar V S, Gupta V D, Patil V S, Umape P
G, Sekar N. Synth Commun, 2012, 42: 1349
24 Niknam K, Saberi D, Sadegheyan M, Deris A. Tetrahedron
Lett, 2010, 51: 692
33 Karimi-Jaberi Z, Pooladian B. Sci World J, 2012: 208796
34 Karimi-Jaberi Z, Arjmandi R. Monatsh Chem, 2011, 142: 631
35 Karimi-Jaberi Z, Abbasi S Z, Pooladian B, Jokar M. E-J Chem,
2011, 8: 1895
25 Niknam K, Mirzaee S. Synth Commun, 2011, 41: 2403
26 Tale N P, Tiwari G B, Karade N N. Chin Chem Lett, 2011, 22:
1415
36 Karimi-Jaberi Z, ReyazoShams M M. Heterocycl Commun,
2011, 17: 177
27 Tayebi S, Baghernejad M, Saberi D, Niknam K. Chin J Catal,
2011, 32: 1477