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

Article abstract of DOI:10.1080/00397911.2011.557516

A simple and efficient method has been developed for the synthesis of 4,4-(arylmethylene)bis(1H-pyrazol-5-ols) by the condensation reaction between substituted aldehydes, and 1-phenyl-3-methylpyrazol-5-one in the presence of xanthan sulfuric acid (XSA) as

Full text of DOI:10.1080/00397911.2011.557516

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Xanthan Sulfuric Acid: An Efficient,
Biosupported, and Recyclable Solid
Acid Catalyst for the Synthesis of 4,4′-
(Arylmethylene)bis(1H-pyrazol-5-ols)
B. Suresh Kuarm a & B. Rajitha a
a Department of Chemistry, National Institute of Technology,
Warangal, India
Accepted author version posted online: 15 Dec 2011.Version of
record first published: 14 May 2012.
To cite this article: B. Suresh Kuarm & B. Rajitha (2012): Xanthan Sulfuric Acid: An Efficient,
Biosupported, and Recyclable Solid Acid Catalyst for the Synthesis of 4,4′-(Arylmethylene)bis(1H-
pyrazol-5-ols), Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 42:16, 2382-2387
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Synthetic Communications1, 42: 2382–2387, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.557516
XANTHAN SULFURIC ACID: AN EFFICIENT,
BIOSUPPORTED, AND RECYCLABLE SOLID
ACID CATALYST FOR THE SYNTHESIS OF
4,4’-(ARYLMETHYLENE)BIS(1H-PYRAZOL-5-OLS)
B. Suresh Kuarm and B. Rajitha
Department of Chemistry, National Institute of Technology, Warangal, India
GRAPHICAL ABSTRACT
Abstract A simple and efficient method has been developed for the synthesis of 4,40-
(arylmethylene)bis(1H-pyrazol-5-ols) by the condensation reaction between substituted
aldehydes, and 1-phenyl-3-methylpyrazol-5-one in the presence of xanthan sulfuric acid
(XSA) as a solid acid catalyst. This method is simple and cost-effective with short reaction
times. Yields are excellent with high purity, and the catalyst could be easily recycled.
Keywords Aldehydes;
1-phenyl-3-methylpyrazol-5-one; xanthan sulfuric acid
4,40-(arylmethylene)bis(1H-pyrazol-5-ols);
biosupported;
INTRODUCTION
Synthesis of nitrogen-containing heterocyclic systems occupies an important
role in the realm of natural and synthetic organic chemistry because of their thera-
peutic and pharmacological properties.[1] In particular, pyrazoles and their deriva-
tives have attracted considerable attention because of their wide variety of
biological activities, including anti-inflammatory,[2] antipyretic,[3] gastric secretion
stimulatory,[4] antidepressant,[5] antibacterial,[6] antifilarial,[7] bactericidal, fungi-
cidal,[8] and promising inhibitory activities against monoamine oxidase for the treat-
ment of diseases such as Parkinson’s and Alzheimer’s.[9] The conventional chemical
approach to 4,40-(arylmethylene)bis(3-methyl-1-phenyl-pyrazol-5-ols) involves the
successive Knoevenagel synthesis of the corresponding arylidenepyrazolones, its
base-promoted Michael reaction, and one-pot tandem Knoevenagel–Michael
Received November 23, 2010.
Address correspondence to B. Rajitha, Department of Chemistry, National Institute of
Technology, Warangal, India. E-mail: rajithabhargavi@ymail.com
2382

4,40-(ARYLMETHYLENE)BIS(1H-PYRAZOL-5-OLS)
2383
reaction of arylaldehydes with 2 equiv. of 5-methyl-2-phenyl-2,4-dihydro-3H-
pyrazol-3-one performed under a variety of reaction conditions.[10,11] The first set
of procedures utilizes the catalysis of the components with piperidine in ethanolic sol-
ution.[12] The second set of methods involves the uncatalyzed tandem Knoevenagel–
Michael reaction under neutral conditions in either ethanol[13] or benzene[14]
solutions. Although it affords the corresponding 4,40-(arylmethylene)bis(1H-
pyrazol-5-ols) in reliable 70–90% yields, the reaction requires 3–12 h of initial reflux
with a further 24 h under ambient temperature to go to completion. Wang et al.[15]
reported its synthesis in water using sodium dodecyl sulfate as the surfactant catalyst
over a 1-h period, but the process needs a temperature of 100 ꢀC. Finally, Elinson
et al. utilized electrocatalytic procedure for its synthesis.[16] Further, Perumal and
coworkers reported the synthesis and antiviral activity of 4,40-(arylmethylene)bis(3-
methyl-1-phenyl-1H-pyrazol-5-ols) using ceric ammonium nitrate (CAN) as a cata-
lyst.[17] However, most of the methods suffer from at least one limitation that may
include moderate yields, long reaction times, harsh reaction conditions, or tedious
workup procedures. Therefore, the search continues for a better catalyst for the
synthesis of 4,40-(arylmethylene)bis(3-methyl-1-phenyl-pyrazol-5-ols) in terms of
operational simplicity, reusability of catalyst, low cost, and greater selectivity.
Xanthan and its derivatives[18–20] have some unique properties that make them
attractive alternatives for conventional organic or inorganic supports for catalytic
applications. Xanthan is the most abundant bacterial exopolysaccharide in the
world, which is produced through fermentation, and it has been widely studied dur-
ing recent decades, as it is a biodegradable material and a renewable resource. Unlike
other gums, it is very stable under a wide range of temperatures and pH values.
[21]
Xanthan sulfuric acid
can be easily prepared by the reaction of xanthan with
chlorosulfonic acid; the number of acidic (Hþ) sites in the xanthan sulfuric acid
determined by acid–base titration was 0.6 meq=g.
RESULTS AND DISCUSSION
Our research group has developed various new synthetic methodologies for the
synthesis of both building blocks and heterocyclic compounds using new reagents.[22]
Thus, in continuation of our interest in the development of new methodologies, we
describe herein the synthesis of a 4,40-(arylmethylene)bis(3-methyl-1-phenyl-
pyrazol-5-ols) in ethanol catalyzed by xanthan sulfuric acid (Scheme 1).
We investigated the efficiency of xanthan sulfuric acid compared to various sul-
fur analog acidic catalysts. The results are summarized in Table 1. Xanthan sulfuric
Scheme 1. Synthesis of 4,40-(arylmethylene)bis(1H-pyrazol-5-ols) with xanthan sulfuric acid.

2384
B. SURESH KUARM AND B. RAJITHA
Table 1. Effect of catalysts on yield
Entry
Catalyst
Yield (%)a
1
2
3
4
Xanthan sulfuric acid
Silica sulfuric acid
Sulfuric acid in acetic acid
No catalyst
95
88
52
15
aIsolated yield.
Table 2. Influence of the catalytic amounts of xanthan sulfuric acid
Entry
Catalyst (g)
Time (min)
Yield (%)a
1
2
3
4
5
6
None
0.01
0.03
0.05
0.08
0.08
60
15
15
15
30
15
Trace
25
55
79
95
95
aIsolated yield.
acid was found to be the most effective catalyst based on the product yield. The reac-
tion did not proceed in the absence of catalyst (yield less than 15%).
We examined the amount of catalyst required in this reaction. The best results
were obtained using 0.08 g of catalyst (95%). Using lesser amounts of catalyst
resulted in lesser yields, and in the absence of catalyst the yield of the product was
found to be very poor Table 2.
EXPERIMENTAL
All the melting points are uncorrected. The progress of the reaction was mon-
itored by thin-layer chromatography (TLC). Infrared (IR) spectra (KBr) were
1
recorded on a Shimadzu FTIR model 8010 spectrometer, and the H NMR spectra
was determined on a Varian Gemini 200-MHz spectrometer using tetramethylsilane
(TMS) as internal standard. Mass spectra were recorded on a Jeol JMS D-300 spec-
trometer. CHN analysis was done on a Carlo Erba EA 1108 automatic elemental
analyzer. All solvents and reagents were purchased from Aldrich and Fluka.
Typical Procedure
A mixture of aldehyde (1 mmol), 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-
3-one (2 mmol), and xanthane sulfuric acid (0.08 g) in ethanol (5 mL) was heated
under refluxing conditions for an appropriate time according to Table 3. After the
completion of the reaction (as monitored by TLC), the reaction mixture was filtered
and washed with ethanol (2 ꢁ 20 mL) to separate the catalyst. Then the filtrate was
evaporated under reduced pressure to afford a pure product. Further purification

4,40-(ARYLMETHYLENE)BIS(1H-PYRAZOL-5-OLS)
2385
Table 3. Synthesis of 4,40-(arylmethylene)bis(1H-pyrazol-5-ols) with xanthan sulfuric acid
Entry
Aldehydes
Product Time (min) Yield (%)a
Mp (ꢀC)
1
2
Benzaldehyde
3-Methylbenzaldehyde
4-Methylbenzaldehyde
3a
3b
3c
3d
3e
3f
15
25
25
25
30
15
25
20
25
15
25
30
30
95
91
90
92
91
90
90
94
92
95
85
78
76
166–167[16]
[17]
242–243
3
203–204[17]
165–168[23]
152–153[15]
230–232[15]
236–237[15]
207–209[15]
148[11]
4
3-Hydroxybenzaldehyde
4-Hydroxybenzaldehyde
4-Nitrobenzaldehyde
5
6
7
2-Chlorobenzaldehyde
4-Chlorobenzaldehyde
3g
3h
3i
8
9
4-Methoxybenzaldehyde
2-Furfuraldehyde
2-Naphthaldehyde
10
11
12
13
3j
189–190[17]
185–186
202
3k
3l
4-Oxo-4H-chromene-3-carbaldehyde
6-Nitro-4-oxo-4H-chromene-3-carbaldehyde
3m
190
aYields refer to pure solid products; all products were characterized by spectral data.
Table 4. Effect of reusability of catalyst on yielda
Run
Cycle
Yield (%)b
1
2
3
4
0
1
2
3
95
92
88
76
aReaction conditions: mixture of benzaldehyde (1 mmol), 5-methyl-2-phe-
nyl-2,4-dihydro-3H-pyrazol-3-one (2 mmol), and xanthane sulfuric acid
(0.08 g) in ethanol (5 mL) was heated under reflux.
bYields refer to the pure, isolated, recovered catalyst.
was followed by crystallization from ethanol. The recovered catalyst was reused for
subsequent runs (Table 4).
Analytical Data
1
Table 3, Entry 11. IR (KBr): 3421, 2949, 1610 cmꢂ1; H NMR (DMSO-d6):
d ¼ 2.33 (s, 6 H, 2 CH3), 5.23 (s, 1H, CH), 6.95–7.78 (m, 17 H, Ar); MS (m=z): 487
(Mþ). Anal. Calcd. for C31H26N4O2: C, 76.52; H, 5.39; N, 11.51; Found: C, 76.25;
H, 5.24; N, 12.10.
1
Table 3, Entry 12. IR (KBr): 3439, 2945, 1604 cmꢂ1; H NMR (DMSO-d6):
d ¼ 2.46 (s, 6 H, 2 CH3), 5.21 (s, 1H, CH), 6.19 (s, 1H, CH) 7.21–7.86 (m, 14 H,
Ar); MS (m=z): 504 (Mþ). Anal. calcd. for C30H24N4O4: C, 71.42; H, 4.79; N,
11.10; found C, 71.21; H, 4.70; N, 11.18.
1
Table 3, Entry 13. IR (KBr): 3411, 2951, 1609 cmꢂ1; H NMR (DMSO-d6):
d ¼ 2.34 (s, 6 H, 2 CH3), 5.24 (s, 1H, CH), 6.21 (s, 1H, CH) 7.18–7.88 (m, 13 H,

2386
B. SURESH KUARM AND B. RAJITHA
Ar); MS (m=z): 549 (Mþ). Anal. calcd. for C30H23N5O6: C, 65.57; H, 4.22; N, 12.74.
found: C, 65.46; H, 4.34; N, 12.61.
CONCLUSION
We have developed a simple and efficient method for the synthesis of 4,40-
(arylmethylene)bis(1H-pyrazol-5-ols) using xanthan sulfuric acid. The short reaction
times, simple workup, good yields, mild reaction conditions, and recyclability of the
catalyst are features of this new procedure.
ACKNOWLEDGMENT
B. S. K. is grateful to the Council of Scientific and Industrial Research, New Delhi,
India, for providing financial support in the form of a senior research fellowship.
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