Pyrazole-4-carboxylic Acids from Vanadium-catalyzed Chemical Transformation of Pyrazole-4-carbaldehydes

Article abstract of DOI:10.1002/jhet.3546

The conversion of aldehydes into carboxylic acids using oxidizing agents is a common protocol in transformation chemistry. An efficient oxidation strategy of transformation of pyrazole-4-aldehydes to the corresponding acids using vanadium catalysts in the presence of 30% H₂O₂ as an oxidant is described. The catalytic technology was successfully applied to a range of various 4-formylpyrazoles, and plausible mechanism is also discussed.

Full text of DOI:10.1002/jhet.3546

Month 2019
Pyrazole-4-carboxylic Acids from Vanadium-catalyzed Chemical
Transformation of Pyrazole-4-carbaldehydes
*
Renu Bala, Poonam Kumari, Sumit Sood, Harshita Phougat, Anil Kumar, and Karan Singh
Department of Chemistry, Akal College of Basic Sciences, Eternal University, Baru Sahib, Sirmour, Himachal Pradesh
173101, India
*E-mail: karansinghji@rediffmail.com; karan.sagwal@yahoo.com
Received October 28, 2018
DOI 10.1002/jhet.3546
Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com).
The conversion of aldehydes into carboxylic acids using oxidizing agents is a common protocol in trans-
formation chemistry. An efficient oxidation strategy of transformation of pyrazole-4-aldehydes to the corre-
sponding acids using vanadium catalysts in the presence of 30% H2O2 as an oxidant is described. The
catalytic technology was successfully applied to a range of various 4-formylpyrazoles, and plausible mech-
anism is also discussed.
J. Heterocyclic Chem., 00, 00 (2019).
INTRODUCTION
carboxylic acids
heterocyclic carboxylic acids has received significant
attention in the recent years.
Among heterocyclic carboxylic acids, pyrazole-4-
Heterocyclic
are
important
intermediates in the synthesis of nitrogen containing
biologically active compounds, pharmaceuticals, and
agrochemicals [1–3]. These organic compounds are
also the precursors for many synthetically useful
scaffolds/building blocks, such as amides, esters,
hydrazides, aldehydes, and alcohols, which can be
converted into various functional groups [4].
The classical approach to carboxylic acids is the
oxidation of corresponding aldehydes and has been
studied extensively till now. The earlier reports for
aldehyde/carboxylic acid conversions were achieved by
several oxidizing agents such as alkaline KMnO4, acidic
KMnO4, MnO2, K2Cr2O7, NaOCl, organoselenenic acids,
and Jone’s reagent [5–13]. The alkaline hydrolysis of
esters is another well-known approach for the preparation
of carboxylic acids [14]. The other methods are also
reported in the literature such as acid hydrolysis of
amides and base-catalyzed hydrolysis of nitriles [15,16].
Hence, it is not surprising that the synthesis of
carboxylic acids possess
armamentarium because of their medicinal and
pharmaceutical activities such as antimicrobial, analgesic,
a
vital place in our
anti-inflammatory,
human
neutrophil
chemotaxis
inhibitors, hypoglycemic agent, potent and selective
hypoxia-inducible factor prolyl hydroxylase inhibitor
(JNJ-42041935), xanthine oxidoreductase inhibitor
(Y-700), prolyl hydroxylase inhibitors, and intermediate
products in the synthesis of drugs for the treatment of
autoimmune diseases [17–23].
To see the potential applications of pyrazole-4-
carboxylic acids in the synthesis of other heterocyclic
compounds and in the synthesis of medicinal drugs, there
is still lot of interest of the scientific community to the
search of new methods/reagents for the preparation of
pyrazole-4-carboxylic acids.
The conversion of aldehydes into carboxylic acids using
oxidizing agents is a common protocol in transformation
chemistry. Recently, Talukdar et al. reported the efficient
© 2019 Wiley Periodicals, Inc.

R. Bala, P. Kumari, S. Sood, H. Phougat, A. Kumar, and K. Singh
Vol 000
oxidative ability of the VO(acac)2/H2O2 system for
the oxidation of aromatic, aliphatic, and heterocyclic
aldehydes to the corresponding acids [24]. On the other
hand, vanadium is a very attractive metal component for
catalysts because of abundant availability in nature and
corresponding low costs as well as low toxicity compared
with other heavy metals [25].
corresponding aldehydes is highly dependent on the
solvent used [24].
In this paper, we report a convenient synthesis of
pyrazole-4-carboxylic acids (2a–p) from pyrazole-4-
carbaldehydes (1a–p) [4,26,29–32] using vanadium
catalyst in the presence of 30% H2O2 in acetonitrile
(Scheme 1).
Owing to the oxidation efficiency and attracted by
the advantageous properties of vanadium catalysts, we
report here the oxidation of pyrazole-4-carbaldehydes in
the presence of vanadium catalysts using H2O2 as an
oxidant.
In our initial experiments, we screened six commercially
available vanadium catalysts for the oxidation of 4-
formylpyrazole 2a, which was chosen as a representative
example for this study. The screening was performed
at 30°C to 70°C using 1 molar equiv of 30% H2O2
in acetonitrile for 5–8 h using 1 mol % of vanadium
catalysts. The results are summarized in Table 1.
Among the six applied commercially available catalysts,
VO(acac)2 showed 32% conversion even after 5 h at 30°C
(Table 1, entry 6). When the same reaction was run for 8 h
at 30°C, then 43% conversion was observed (Table 1, entry
7). We were pleased to observe 56% conversion of
aldehyde 2a to carboxylic acid 3a proceeding at 70°C for
8 h. On further heating at 70°C for 12 h, there is not
much effect observed on conversion of aldehyde 2a to
carboxylic acid 3a.
RESULTS AND DISCUSSION
Standard methods for the oxidation of 4-formylpyrazoles
involve the use of oxidizing reagent such as KMnO4/
pyridine [26], oxone in aqueous dimethylformamide [27],
and KMnO4/Na2HPO4 [28], which are not in high demand
with respect to industry and environment. Literature
search indicated that hydrogen peroxide is green oxidizing
agent because of water as byproduct. The oxidizing
ability of hydrogen peroxide may be increased by the
addition of ligand to the reaction mixture. Talukdar et al.
reported V2O5/H2O2 and five coordinate VO(acac)2
as good oxidation catalyst, and acids formation from
For further optimization of this reaction, VO(acac)2
catalyst was selected, which showed 56% conversion
(43% isolated yield of 3a) already in the initial
experiments under no optimized conditions (Table 1,
Scheme 1. Synthesis of pyrazole-4-carboxylic acids (2a–p) from pyrazole-4-carbaldehydes (1a–p).
Table 1
Screening results of vanadium catalysts for the oxidation of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (2a).
Entry
Catalyst (1 mol %)
Temperature (°C)
Time (h)
Conversiona (%)
1
2
3
4
5
6
7
8
V2O5
NH4VO3
VOSO4
VO(OEt)3
NaVO3
VO(acac)2
VO(acac)2
VO(acac)2
70
70
70
70
70
30
30
70
8
8
8
8
8
5
8
8
11
20
0
6
16
32
43
56
aDetermined by 1H-NMR spectroscopy via comparison of substrate and product integrals.
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Month 2019
Vanadium-catalyzed Synthesis of Pyrazole-4-carboxylic Acids
entry 8). To check the effects of various solvents,
molar equivalent of 30% H2O2 and optimal loading of
vanadium catalyst on the representative compound 2a,
an optimization study was carried out by performing a
series of experiments. All optimization experiments were
performed at a reaction temperature of 70°C (determined
as optimal temperature) for 5–8 h. The results are
summarized in Table 2.
It was found that in the absence of catalyst, only 10%
products were formed (Table 2, entry 1), and in the
absence of hydrogen peroxide, no product formation was
observed (Table 2, entry 2). This implies that H2O2 alone
was not able to provide oxidized product in good yield.
To our delight, when the reaction was performed with
4 mol % of VO(acac)2 and 3 molar equiv of 30% H2O2
in acetonitrile at 70°C, considerable improvement in the
yield (88%, entry 7) was achieved.
Encouraged by these results on the oxidation of
aldehyde 2a, we further investigated the effects of
oxidants on the oxidation using VO(acac)2 catalysts. The
results are summarized in Table 3.
Among the oxidants screened for the oxidation of
aldehyde 2a, 30% H2O2 was observed as the best oxidant.
When the oxidation reaction was performed under 1 atm
of oxygen at 70°C, then only 40% of product 3a was
isolated (Table 3, entry 2). In contrast, the addition of
3 molar equiv of tert-butyl hydroperoxide showed almost
no improvement (Table 3, entries 3–5). The oxidation
reaction performed using 3 molar equiv of 30% H2O2 at
70°C for 8 h afforded 95% of oxidized product 3a
(Table 3, entry 8). In contrast, the addition of 4 molar
equiv of 30% H2O2 and increase in the reaction time
showed no improvement in the isolated yield. Thus, the
reaction condition of entry 8 of Table 3 was considered as
the optimized condition for further extend of the scope
and generality of the procedure employing a variety of
substituents on pyrazole ring. Indeed, a series of pyrazole-
4-carboxylic acid derivatives 3b–p could easily be
synthesized within 5–8 h and in good-to-excellent yields
(71–95%) (Scheme 2).
Table 2
Solvent/molar equivalent of 30% H2O2/mol % of VO(acac)2 catalyst
screening for the synthesis of compound 3a.
Catalyst
30% H2O2
(molar equiv)
VO(acac)2
(mol %)
Time
(h)
Yield
(%)a
Entry
Solvent
1
2
3
4
5
6
7
8
9
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
Toluene
CH2Cl2
Dioxane
1
—
1
1.5
2
2
3
3
3
—
1
1
1
2
3
4
4
4
4
8
8
8
8
7
6
5
8
8
8
10
0
43
51
62
71
88
45
49
61
The plausible mechanism of oxidation of aldehydes to
carboxylic acid involving peroxovanadium species has
been illustrated in Scheme 3.
First, the treatment of VO(acac)2 with 30% hydrogen
peroxide resulted in the formation of
a reactive
10
3
peroxovanadium intermediate II. The metal peroxo
oxygen atom of intermediate II attacks on the
aIsolated yield.
Table 3
Effect of oxidants on the oxidation of aldehyde 2a.
Entry
Oxidant (equiv/atm)
O2 (1 atm)
O2 (1 atm)
TBHP (1.5 equiv)
TBHP (3.0 equiv)
TBHP (3.0 equiv)
30% H2O2 (1.5 equiv)
30% H2O2 (3.0 equiv)
30% H2O2 (3.0 equiv)
30% H2O2 (3.0 equiv)
30% H2O2 (4.0 equiv)
Temperature (°C)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
30
70
30
30
70
70
70
70
70
70
12
12
12
12
12
8
5
8
12
8
10
40
15
25
27
56
88
95
76
79
10
aIsolated yield.
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R. Bala, P. Kumari, S. Sood, H. Phougat, A. Kumar, and K. Singh
Vol 000
Scheme 2. Substrate scope for the oxidation of pyrazole-4-carbaldehydes 2a–p using vanadium catalyst VO(acac)2.
Scheme 3. Plausible mechanism for the oxidation of 4-formylpyrazoles to pyrazole-4-carboxylic acids.
electrophilic carbon of the formyl group of pyrazoles
affording the corresponding pyrazole-4-carboxylic acids
(Scheme 3).
The structures of all unknown compound 3 were
1
characterized by their IR, H-NMR, 13C-NMR, and mass
spectral analysis. In general, IR spectra of compound 3
Journal of Heterocyclic Chemistry
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Month 2019
Vanadium-catalyzed Synthesis of Pyrazole-4-carboxylic Acids
Table 4
Physical data of 4-formylpyrazoles 2j–p.
Compound
R
R0
Yield (%)
mp (°C)
Formula
2j
2k
2l
2m
2n
2o
2p
C6H5
4-OMeC6H4
C6H5
Benzothiazol-2-yl
6-Methylbenzothiazol-2-yl
6-Methylbenzothiazol-2-yl
6-Bromobenzothiazol-2-yl
Benzothiazol-2-yl
80
71.5
65
81
65
132–134
160–162
149–151
166–168
154–156
159–161
146–148
C17H11N3OS
C19H15N3O2S
C18H13N3OS
C17H10BrN3OS
C17H10ClN3OS
C18H12ClN3OS
C18H13N3O2S
C6H5
4-ClC6H4
4-ClC6H4
4-OMeC6H4
6-Methylbenzothiazol-2-yl
Benzothiazol-2-yl
66
77
Table 5
Physical data of pyrazole-4-carboxylic acids 3a–p.
Compound
R
R0
Yield (%)
mp (°C) [26,32]
Formula
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
C6H5
4-ClC6H4
4-BrC6H4
4-EtC6H4
4-PhC6H4
C6H5
4-MeC6H4
4-OMeC6H4
4-ClC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
95
90
92
85
80
84
89
91
87
83
76
89
81
85
71
80
205–206 (204–205)
238–240 (240–242)
250–251 (249–250)
204–205 (200–202)
196–198 (198–199)
260–261 (262, d)
256–259 (258, d)
264–257 (265, d)
261–263 (261, d)
230–232
C16H12N2O2
C16H11ClN2O2
C16H11BrN2O2
C18H16N2O2
C22H16N2O2
4-H2NO2SPh
4-H2NO2SPh
4-H2NO2SPh
4-H2NO2SPh
C22H18N3O4S
C23H20N3O4S
C23H20N3O5S
C22H17ClN3O4S
C17H11N3O2S
C19H15N3O3S
C18H13N3O2S
C17H10BrN3O2S
C17H10ClN3O2S
C18H12ClN3O2S
C18H13N3O3S
Benzothiazol-2-yl
6-Methylbenzothiazol-2-yl
6-Methylbenzothiazol-2-yl
6-Bromobenzothiazol-2-yl
Benzothiazol-2-yl
6-Methylbenzothiazol-2-yl
Benzothiazol-2-yl
4-OMeC6H4
C6H5
309–311
258–260
303–306
350–355
300–302
227–231
C6H5
4-ClC6H4
4-ClC6H4
4-OMeC6H4
showed characteristics band in the range 1694–1707 cmꢀ1
,
carbaldehyde based on the use of vanadium and hydrogen
peroxide as a green oxidizing agent. This technology will
make it appealing to the synthetic organic chemists
interested in green chemistry and because of simplicity
and catalytic nature of this protocol.
which corresponds to C═O stretch of carboxylic group. A
weak broad band in the range 2564–3070 cmꢀ1 was also
observed in the IR spectra of compound 3, which were
due to O─H stretching. 1H-NMR spectra of these
compounds were characterized by a broad, one proton
singlet displaying at δ 12.80, a one proton singlet at δ
8.94–9.01 attributed to C5─H of pyrazole ring.
EXPERIMENTAL
Melting points were determined in open glass capillaries
CONCLUSIONS
on a Fisher–Johns melting point apparatus and were
uncorrected. H-NMR (400 MHz) spectra were recorded
1
In conclusion, we developed an efficient catalytic
technology for the oxidation of a range of pyrazole-4-
at room temperature in DMSO-d6 as solvent and
tetramethylsilane as an internal standard (δ = 0 ppm), and
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R. Bala, P. Kumari, S. Sood, H. Phougat, A. Kumar, and K. Singh
Vol 000
the values were reported in the following order: chemical
shift (δ in ppm), multiplicity (s, singlet; d, doublet; t,
triplet; q, quartet; and m, multiplet), coupling constants
(J in Hz), and integration. 13C-NMR (100 MHz) spectra
were recorded in CDCl3 solutions with tetramethylsilane
as internal standard. IR spectra were taken as KBr
pellets on a PerkinElmer RXI FT-IR spectrometer. The
mass spectra were recorded on a JEOL JMS 600
mass spectrometer at an ionizing potential of 70-eV
electron impact ionization mode using the direct inlet
system. All the reactions were monitored by thin-layer
chromatography on precoated silica gel 60 F254 (mesh);
spots were visualized under UV light at 254 nm.
The 4-formylpyrazoles, that is, 1,3-diphenyl-
1H-pyrazole-4-carbaldehyde (2a), 3-(4-chlorophenyl)-1-
phenyl-1H-pyrazole-4-carbaldehyde (2b), 3-(4-bromophe-
nyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (2c), 3-(4-
ethylphenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde (2d),
3-([1,10-biphenyl]-4-yl)-1-phenyl-1H-pyrazole-4-carbalde-
DMSO-d6): δ 8.98 (s, 1H, pyrazole─H), 8.01 (d,
J = 7.9 Hz, 1H, Ar─H), 7.93 (d, J = 7.9 Hz, 1H, Ar─H),
7.85–7.88 (m, 2H, Ar─H), 7.52 (dt, J = 8.2 Hz, 1H,
Ar─H), 7.40–7.47 (m, 4H, Ar─H). 13C-NMR (100 MHz,
CDCl3): δ 167.5, 155.4, 133.6, 132.6, 130.3, 129.9,
129.0, 128.8, 126.9, 125.5, 123.4, 122.9, 121.8. ESI-MS
(m/z): 322.0 [M + H]+ (100%). Anal. Calcd. for
C17H11N3O2S: C, 63.54; H, 3.45%. Found: C, 63.61; H,
3.51%.
3-(4-Methoxyphenyl)-1-(6-methylbenzo[d]thiazol-2-yl)-1H-
pyrazole-4-carboxylic acid 3k.
Obtained as white solid,
yield 76%; mp 309–311°C. IR (υ cmꢀ1, KBr): 1694
(C═O str), 2574–3060 (OH str), 1610 (C═N str). 1H-
NMR (400 MHz, DMSO-d6):
δ
8.94 (s, 1H,
pyrazole─H), 7.80–7.85 (m, 4H, Ar─H), 7.34 (d,
J = 8.3 Hz, 1H, Ar─H), 7.00 (d, J = 8.4 Hz, 2H, Ar─H),
3.85 (s, 3H, OCH3), 2.48 (s, 3H, CH3). 13C-NMR
(100 MHz, CDCl3): δ 165.6, 158.4, 153.3, 143.8, 136.6,
135.8, 135.3, 130.0, 128.4, 122.9, 121.9, 113.8, 55.1,
21.1. ESI-MS (m/z): 366.0 [M + H]+ (100%). Anal.
Calcd. for C19H15N3O3S: C, 62.45; H, 4.14%. Found: C,
hyde
(2e),
4-(4-formyl-3-phenyl-1H-pyrazol-1-yl)
benzenesulfonamide (2f), 4-(4-formyl-3-(p-tolyl)-1H-
pyrazol-1-yl)benzenesulfonamide (2g), 4-(4-formyl-3-
(4-methoxyphenyl)-1H-pyrazol-1-yl)benzenesulfonamide
(2h), and 4-(3-(4-chlorophenyl)-4-formyl-1H-pyrazol-1-yl)
benzenesulfonamide (2i), were prepared by the reporting
procedures [4,26].
62.57; H, 4.23%.
1-(6-Methylbenzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazole-4-
carboxylic acid 3l. Obtained as white solid, yield 89%; mp
258–260°C. IR (υ cmꢀ1, KBr): 1706 (C═O str), 2574–
3060 (OH str), 1599 (C═N str). 1H-NMR (400 MHz,
DMSO-d6): δ 8.96 (s, 1H, pyrazole─H), 7.80–7.86 (m,
4H, Ar─H), 7.45–7.47 (m, 3H, Ar─H), 7.34 (dd, J = 8.2
and 1.8 Hz, 1H, Ar─H), 2.48 (s, 3H, CH3). 13C-NMR
(100 MHz, CDCl3): δ 164.3, 157.8, 153.6, 148.1, 135.2,
133.1, 129.5, 128.6, 128.5, 128.3, 128.0, 125.6, 123.1,
121.9, 21.1. ESI-MS (m/z): 336.0 [M + H]+ (100%).
Anal. Calcd. for C18H13N3O2S: C, 64.46; H, 3.91%.
Preparation of 4-formylpyrazoles 2j–p.
A mixture
of hydrazone 1 (3.47 mmol) and OPC-VH reagent
(10.41 mmol) in dioxane (25 mL) was stirred at 60°C for
4 h. After complete consumption of the starting material,
the reaction mixture was cooled to room temperature
and poured into ice water. The solid then separated on
neutralization with NaHCO3 was filtered, washed with
water, and crystallized from ethanol to afford pyrazole-4-
carbaldehyde 2 [29] (Table 4).
Found: C, 64.61; H, 3.83%.
1-(6-Bromobenzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazole-4-
carboxylic acid 3m. Obtained as white solid, yield 81%;
mp 303–306°C. IR (υ cmꢀ1, KBr): 1699 (C═O str),
2564–3060 (OH str), 1594 (C═N str). 1H-NMR
(400 MHz, DMSO-d6): δ 8.96 (s, 1H, pyrazole─H), 8.19
(d, J = 1.9 Hz, 1H, Ar─H), 7.85–7.88 (m, 2H, Ar─H),
7.82 (d, J = 8.7 Hz, 1H, Ar─H), 7.62 (dd, J = 8.7,
1.9 Hz Ar─H), 7.43–7.46 (m, 3H, Ar─H). 13C-NMR
(100 MHz, CDCl3): δ 166.5, 159.7, 149.3, 135.9, 135.0,
130.1, 129.7, 128.7, 128.4, 125.1, 123.8, 123.4, 117.9.
ESI-MS (m/z): 402.0 [(M + H)+, 81Br], 400.0 [(M + H)+,
79Br]. Anal. Calcd. for C17H10BrN3O2S: C, 51.01; H,
General
procedure
for
the
synthesis
of
pyrazole-4-carboxylic acids (3a–p). VO(acac)2 (4.26 mg,
4 mol %) was dissolved in 30% H2O2 (1.2 mmol);
the color of the mixture changed to reddish brown. To
this mixture, 1,3-diphenyl-1H-pyrazole-4-carbaldehyde
(100 mg, 0.402 mmol) dissolved in the minimum amount
of MeCN was added, and the mixture was stirred for 8 h
at 70°C. Progress of the reaction was monitored by thin-
layer chromatography. On completion of the reaction,
MeCN was removed under reduced pressure, and H2O
was added (3 mL). The product was extracted with
EtOAc (3 × 10 mL), and the organic layer was dried over
anhyd Na2SO4. Evaporation of organic solvent afforded
1,3-diphenyl-1H-pyrazole-4-carboxylic acid 3a in 95%
2.52%. Found: C, 51.11; H, 2.59%.
1-(Benzo[d]thiazol-2-yl)-3-(4-chlorophenyl)-1H-pyrazole-4-
carboxylic acid 3n. Obtained as white solid, yield 85%;
mp 350–355°C. IR (υ cmꢀ1, KBr): 1700 (C═O str),
2579–3070 (OH str), 1600 (C═N str). 1H-NMR
(400 MHz, DMSO-d6): δ 9.01 (s, 1H, pyrazole─H), 8.07
(d, J = 7.8 Hz, 1H, Ar─H), 7.89 (d, J = 8.5 Hz, 2H,
Ar─H), 7.55 (t, J = 7.8 Hz, 1H, Ar─H), 7.50 (d,
J = 8.5 Hz, 2H, Ar─H), 7.45 (t, J = 8.0, 1H, Ar─H).
yield (Table 5).
1-(Benzo[d]thiazol-2-yl)-3-phenyl-1H-pyrazole-4-carboxylic
acid 3j. Obtained as white solid, yield 83%; mp 230–
232°C. IR (υ cmꢀ1, KBr): 1707 (C═O str), 2574–3060
(OH str), 1599 (C═N str). 1H-NMR (400 MHz,
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Month 2019
Vanadium-catalyzed Synthesis of Pyrazole-4-carboxylic Acids
ESI-MS (m/z): 358.0 [(M + H)+, 37Cl], 356.0 [(M + H)+,
35Cl]. Anal. Calcd. for C17H10ClN3O2S: C, 57.39; H,
2.83%. Found: C, 57.21; H, 2.93%.
3-(4-Chlorophenyl)-1-(6-methylbenzo[d]thiazol-2-yl)-1H-
[6] Bawn, C. E. H.; Jolley, J. Proc R Soc Lond A 1956, 237, 297.
[7] Brzaszcz, M.; Kloc, K.; Maposah, M.; Mlochowski, J. Synth
Commun 2000, 30, 4425.
[8] Chakraborty, D.; Gowda, R. R.; Malik, P. Tetrahedron Lett
2009, 50, 6553.
pyrazole-4-carboxylic acid 3o.
Obtained as white solid,
[9] Dalcanale, E.; Montanari, F. J Org Chem 1986, 51, 567.
[10] Graham, G. T.; Westheimer, F. J Am Chem Soc 1958, 80,
3030.
[11] Jeong, S. Y.; Kim, N.; Lee, J. C. Bull Korean Chem Soc 2014,
35, 3366.
yield 71%; mp 300–302°C. IR (υ cmꢀ1, KBr): 1704
(C═O str), 2666–2923 (OH str), 1605 (C═N str). 1H-
NMR (400 MHz, DMSO-d6):
δ
8.96 (s, 1H,
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pyrazole─H), 7.89 (d, J = 8.6 Hz, 2H, Ar─H), 7.80–7.82
(m, 2H, Ar─H), 7.48 (d, J = 8.6 Hz, 2H, Ar─H), 7.34
(dd, J = 8.6 and 1.2 Hz, 1H, Ar─H), 2.47 (s, 3H, CH3);
13C-NMR (100 MHz, CDCl3): δ 168.4, 158.3, 148.1,
133.1, 130.3, 128.5, 123.1, 122.0, 21.1. ESI-MS (m/z):
372.0 [(M + H)+, 37Cl], 370.0 [(M + H)+, 35Cl]. Anal.
Calcd. for C18H12ClN3O2S: C, 58.46; H, 3.27%. Found:
C, 58.57; H, 3.33%.
1-(Benzo[d]thiazol-2-yl)-3-(4-methoxyphenyl)-1H-pyrazole-
4-carboxylic acid 3p. Obtained as white solid, yield 80%;
mp 227–231°C. IR (υ cmꢀ1, KBr): 1694 (C═O str), 2578–
2959 (OH str), 1610 (C═N str). 1H-NMR (400 MHz,
DMSO-d6): δ 12.80 (bs, 1H, COOH), 8.97 (s, 1H,
pyrazole─H), 8.03 (d, J = 7.8 Hz, 1H, Ar─H), 7.93 (d,
J = 8.0 Hz, 1H, Ar─H), 7.85 (d, J = 8.8 Hz, 2H, Ar─H),
7.53 (t, J = 8.2 Hz, 1H, Ar─H), 7.43 (t, J = 8.0 Hz, 1H,
Ar─H), 7.05 (d, J = 8.8 Hz, 2H, Ar─H), 3.85 (s, 3H,
OCH3); 13C-NMR (100 MHz, CDCl3): δ 169.5, 160.9,
155.1, 150.7, 133.6, 133.0, 130.4, 126.9, 125.4, 123.3,
122.8, 122.7, 121.7, 114.2, 55.4. ESI-MS (m/z): 352.0
[M + H]+ (100%). Anal. Calcd. for C18H13N3O3S: C,
61.53; H, 3.73%. Found: C, 61.63; H, 3.83%.
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Acknowledgments. The authors are grateful to Prof. H. S.
Dhaliwal, Vice-Chancellor, Eternal University, Baru Sahib, for
providing the necessary infrastructural facilities and financial
assistance. The authors would like to acknowledge RSIC,
Punjab University, Chandigarh, for recording the analytical data
during this study.
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of the
article.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet