1,3-Dipolar cycloaddition of chalcones and arylidene-1,3-dicarbonyls with diazosulfone for the regioselective synthesis of functionalized pyrazoles and pyrazolines

Article abstract of DOI:10.1016/j.tet.2018.04.030

A convenient method for the synthesis of 3-acylpyrazoles and pyrazole-3-carboxylates using diazosulfone as a reactive 1,3-dipole and a diazomethane equivalent is reported here. Chalcones, arylidenemalonates and other arylidene-1,3-dicarbonyls performed we

Full text of DOI:10.1016/j.tet.2018.04.030

Accepted Manuscript
1,3-Dipolar cycloaddition of chalcones and arylidene-1,3-dicarbonyls with
diazosulfone for the regioselective synthesis of functionalized pyrazoles and
pyrazolines
Deepa Nair, Prashant Pavashe, Irishi N.N. Namboothiri
PII:
S0040-4020(18)30409-5
10.1016/j.tet.2018.04.030
TET 29445
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 6 March 2018
Revised Date: 10 April 2018
Accepted Date: 12 April 2018
Please cite this article as: Nair D, Pavashe P, Namboothiri INN, 1,3-Dipolar cycloaddition of chalcones
and arylidene-1,3-dicarbonyls with diazosulfone for the regioselective synthesis of functionalized
pyrazoles and pyrazolines, Tetrahedron (2018), doi: 10.1016/j.tet.2018.04.030.
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1,3-Dipolar cycloaddition of chalcones and arylidene-1,3-dicarbonyls with diazosulfone for the
regioselective synthesis of functionalized pyrazoles and pyrazolines
Deepa Nair, Prashant Pavashe, Irishi N. N. Namboothiri
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai-400076, India.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
1,3-Dipolar cycloaddition of chalcones and arylidene-1,3-dicarbonyls with
diazosulfone for the regioselective synthesis of functionalized pyrazoles and
pyrazolines
Deepa Nair, Prashant Pavashe, Irishi N. N. Namboothiri
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai-400076, India.
ARTICLE INFO
ABSTRACT
A convenient method for the synthesis of 3-acylpyrazoles and pyrazole-3-carboxylates using
diazosulfone as a reactive 1,3-dipole and a diazomethane equivalent is reported here. Chalcones,
arylidenemalonates and other arylidene-1,3-dicarbonyls performed well as the dipolarophiles in
the reaction with the diazosulfone which took place under simple base mediated conditions
(Cs2CO3 or NaOEt in EtOH). In few cases, the initial cycloadducts, the intermediate pyrazoline
derivatives, could also be isolated and characterized. The pyrazoline derivatives undergo an
alkoxide mediated 1,4-elimination, viz. decarboxylation-detosylation to afford the pyrazole
derivatives.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
Chalcones
Arylidene-1,3-dicarbonyls
Diazosulfone
3-substituted pyrazoles
Decarboxylation-detosylation
2009 Elsevier Ltd. All rights reserved
.
———
Corresponding author. Tel.: +0-000-000-0000; E-mail address: irishi@chem.iitb.ac.in

2
Tetrahedron
ACCEPTED MANUSCRIPT
1. Introduction
which do not have good leaving group were chosen for reaction with
α-diazo-β-ketosulfone and demonstrate the above possibility. This
would also be a novel application of α-diazo-β-ketosulfone as a safe
diazomethane equivalent.
Pyrazole is one of the most important N-heterocycles due to its wide
occurrence, various applications and ease of synthesis.1 Pyrazole
moiety is present in several natural products and designed drug
molecules.2 Natural products such as withasomnine, pyrazofurin,
formycin, fluviol etc and drug molecules such as Celecoxib,
Lonazolac, Rimonabant, Viagra etc contain a pyrazole moiety.2
Possible applications of other pyrazole derivatives in medicinal
chemistry,3 for instance, as anticancer, antitubercular, anti-obesity,
anti-mycobacterial, anti-metabolite, anti-inflammatory and anti-
microbial agents are highlighted in the recent literature.4 Pyrazole
derivatives are also employed in crop protection,5 as ligands in
synthesis6 and as N-heterocyclic carbene precursors.7
2. Results and discussion
At the outset, we treated a representative chalcone 1a with sulfone 2
under the previously optimized conditions, i.e. NaOEt in EtOH,12 at
room temperature and we were pleased to note that the reaction
proceeded smoothly to afford 3-aroyl pyrazole 3a as the exclusive
product (Scheme 2). Moreover, smooth elimination of sulfonyl group
was achieved in a one pot manner without employing harsh reaction
conditions.
General methods for the synthesis of pyrazoles8 include 1,3-dipolar
cycloaddition of diazo compounds with electron deficient
alkenes/alkynes9 and condensation of 1,3-difunctional compounds
with hydrazines.10 As for the synthesis of functionalized pyrazoles, we
and others have demonstrated the application of α-diazo-β-
ketophosphonate (Bestmann-Ohira reagent),11 its corresponding
sulfone12-14 and carboxylate15 analogs for the regioselective synthesis
of pyrazoles bearing, respectively, phosphonate, sulfone and
carboxylate functionalities.16
Although α-diazo-β-ketosulfone has been employed as a carbene
precursor under metal catalysed conditions,17 its application as a
diazoalkane equivalent for cycloaddition with various electron
deficient substrates such as nitroalkenes,12 acetylenes,13 vinyl sulfones
and vinyl sulfonylcarboxylates14 has been investigated only recently.
These cycloadditions led to regioselective synthesis of
sulfonylpyrazoles. However, similar reactions of diazosulfone with
chalcone and alkylidenemalonate remain unreported.
Scheme 2. Reaction of diazosulfone with chalcone
A mechanism proposed for the above reaction is outlined in Scheme
3. The diazosulfone 2 could exist as a resonance hybrid of 2a-c. An
initial deacylation of the intermediate diazo compound I results in the
formation of diazo anion IIa which is stabilized due to the presence of
an electron withdrawing group in the vicinity and is in resonance with
IIb. A 1,3-dipolar cycloaddition of the in situ generated 1,3-dipole IIb
with chalcone 1 ensues and the cycloadduct III thus formed gets
protonated by the solvent EtOH to form intermediate IVa. Two
successive 1,3-proton shifts, IVa to IVb and IVb to IVc, followed by
aromatization via elimination of toluenesulfinic acid delivers pyrazole
3.
NO2
SO2Tol
Ar
O
O
S
Ar
Tol
R
a)
N
O
R
N
Previous work
Ref 12
N2
H
O
O
O
O
P
OEt
OEt
R
Tol
S
O
SO2Tol
N2
N2
RCHO
b)
c)
N
R
Previous work
Ref 13
N
H
SO2Ph
Ar
SO2Tol
Ar
O
O
Tol
E
S
N
O
E
E = H, CO2Et
N
N2
H
Previous work
Ref 14
COR
Ar
H
Ar
ROC
O
O
S
Tol
E
d)
N
O
E = H, COR
Present work
N
N2
H
Scheme 1. Reaction of diazosulfone in the synthesis of pyrazoles
Interestingly, the sulfonyl group is retained in the products formed
from α-diazo-β-ketosulfone and substrates such as nitroalkenes,
acetylenes, vinyl sulfones and vinyl sulfonylcarboxylates (Schemes
1a-c).12-14 This is because of the better leaving group ability of the
dipolarophile derived electron withdrawing group (nitro or sulfonyl)
in the intermediate pyrazoline. We envisioned that in the absence of a
dipolarophile derived leaving group in the intermediate pyrazoline, the
dipole derived sulfonyl group would undergo elimination (Scheme
1d). Therefore, substrates such as chalcones and alkylidenemalonates
Scheme 3. Proposed mechanism for the formation of pyrazole from
diazosulfone and chalcone
Delighted with this result, diversely substituted chalcones were
subjected to cycloaddition with sulfone 2 and the corresponding
products 3 were obtained in moderate to excellent yields (54-94%,
Table 1). Besides parent chalcone 1a, which afforded pyrazole 3a in
moderate yield (54%, entry 1), chalcones 1b-c, possessing a weakly
electron donating substituent at the para position and a weakly
electron withdrawing substituent at the meta position, respectively, on

3
the β-aryl group, afforded the corresponding pyrazoles 3b-c in
ACCEPTED MANUSCRIPT
identical yields (62%, entries 2-3). The reactivity improved when
stronger electron withdrawing substituents such as chloro, fluoro,
cyano and nitro were present on the β-aryl group (1d-i) and the
corresponding pyrazoles 3d-i were obtained in excellent yields (86-
91%) in shorter reaction times (10 min-3 h, entries 4-9). A
representative substituent such as chloro at the para position of the
aroyl ring in conjunction with Ph and substituted aryl group at the β
position as in chalcones 1j-l also afforded the corresponding products
3j-l, though in wider range of yields (70-88%, 3-4 h, entries 10-12).
Subsequently, arylidenemalonates 4 were utilized as efficient
dipolarophiles for reaction with diazosulfone 2 (Tables 2-5). To begin
with, we employed benzylidenemalonate 4a as the model
dipolarophile which reacted with sulfone 2 in the presence of NaOEt
in EtOH in 30 min and afforded a mixture of products, pyrazole-3-
carboxylate 5a and pyrazoline dicarboxylate 6a in 30% and 20%
yields, respectively (entry 1). However, Cs2CO3 turned out to be
superior to NaOEt providing product 5a with complete selectivity in
56% yield (entry 2). While other carbonate bases such as Na2CO3 and
K2CO3 proved less effective both in terms of reaction time and
product yield (entries 3-4), hydroxide bases such as NaOH and KOH
were not found suitable for our reaction (entries 5-6). Lowering the
temperature of the NaOEt mediated reaction to 0oC led to
improvement in the total yield of 5a and 6a (65%, entry 7). At the
same temperature (0oC), Cs2CO3 delivered the product 5a exclusively
in substantially higher yield (70%, entry 8). Lowering the quantity of
Cs2CO3 to 1.2 equiv adversely affected the yield of 5a (50%, entry 9).
On the other hand, gradually lowering the quantity of NaOEt to 1.2
equiv and then to 1.0 equiv tilted the ratio in favor of the intermediate
pyrazoline dicarboxylate 6a (entries 10-11).
Table 1. 1,3-Dipolar cycloaddition of α-diazo-β-ketosulfone with
chalconesa
Entry
Ar1
Ar2
Time
10 h
10 h
3 h
3 h
30 min
10 min
30 min
30 min
3 h
%Yieldb
54
1
3
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
4-
1a
1b
1c
1d
1e
1f
1g
1h
1i
3a
3b
3c
3d
3e
3f
3g
3h
3i
4-MeC6H4
3-BrC6H4
4-ClC6H4
2-ClC6H4
4-FC6H4
4-CNC6H4
4-NO2C6H4
3-NO2C6H4
C6H5
62
62
86
94
95
93
94
91
9
10
4 h
77
1j
3j
ClC6H4
4-
ClC6H4
4-
11
12
4-ClC6H4
4 h
3 h
70
88
1k
1l
3k
3l
3-NO2C6H4
ClC6H4
a Reaction scale: chalcone 1 (0.5 mmol), diazosulfone 2 (1 mmol, 2
equiv) and NaOEt (1 mmol, 2 equiv) in EtOH (7 mL).
b After silica gel column chromatography.
Table 2. Screening of bases
Entry
1
2
3
4
5
6
7
8
9
10
11
Base (equiv)
NaOEt (1.5)
Cs2CO3 (1.5)
Na2CO3 (1.5)
K2CO3 (1.5)
NaOH (1.5)
KOH (1.5)
NaOEt (1.5)
Cs2CO3 (1.5)
Cs2CO3 (1.2)
NaOEt (1.2)
NaOEt (1.0)
Temp
RT
RT
RT
RT
Time/h
30 min
% Yield 5ab
% Yield 6ab
30
56
48
52
42
20c
d
1
6
6
3
2
1
4
4
2.5
5
-
-
-
-
d
d
d
RT
e
e
RT
-
-
0oC
0oC
0oC
0oC
0oC
35
70
50
34
18
30c
d
-
-
d
38c
58c
a Reaction scale: Arylidenemalonate 1 (0.5 mmol), diazosulfone 2 (0.6, 1.2 equiv), EtOH (5 mL).
b After silica gel column chromatography.
c Could not be isolated in pure form as it decomposed during attempted purification.
d Not observed.
e Complex mixture.
Since the Cs2CO3 mediated reaction (Table 2, entry 8) was highly
other hand, a strongly electron donating substitutent such as OMe as
in 4c adversely affected the yield of the corresponding pyrazole 5c
(40%, entry 3). Surprisingly, the intermediate cycloadduct 6d, formed
from malonate 4d, bearing a para-chlorophenyl group, did not
undergo decarboxylation and detosylation and was isolated in 63%
yield (entry 4). On the other hand, malonates bearing stronger
deactivating substituents such as fluoro and cyano at the para position
as in 4e and 4f furnished the corresponding pyrazoles 5e and 5f in
60% and 56% yields, respectively (entries 5 and 6). A strongly
selective for pyrazole carboxylate 5a, the scope of arylidenemalonates
4 was investigated under these conditions (Table 3). Thus, besides
benzylidenemalonate 4a which delivered the corresponding pyrazole
carboxylate 5a in very good yield (70%, entry 1), various other
arylidenemalonates 4b-j were subjected to 1,3-dipolar cycloaddition
with diazosulfone 2 (entries 2-10). Arylidenemalonate 4b, bearing a
weakly electron donating substituent such as Me at the para position,
afforded the corresponding product 5b in 58% yield (entry 2). On the

4
Tetrahedron
electron withdrawing group such as NO2 on the aromatic ring did
e 68% of 4g was recovered.
ACCEPTED MANUSCRIPT
not favor the reaction as almost 70% of the starting material 4g was
recovered (entry 7). In the case of a fused arylidenemalonate such as
4h, the corresponding pyrazole 5h was isolated in low yield (32%,
entry 8). The heteroaryl substituted malonate 4i afforded a complex
mixture when Cs2CO3 was used as base. Therefore, the reaction was
carried out in the presence of 1.5 equiv of NaOEt which fortunately
furnished pyrazole 5i in 58% yield as the only product (entry 9). It
appears that extended conjugation makes the double bond less reactive
as a dipolarophile such as the cinnamaldehyde derived malonate 4j
does not react under our experimental conditions (entry 10).
f NaOEt (1.5 equiv) was used as base as complex mixture was formed
in the presence of Cs2CO3.
g No reaction.
As for the mechanism of the reaction, the first part of which is
similar to that described in Scheme 2, the cycloaddition of the in situ
generated 1,3-dipole IIb with the arylidenemalonate 4 results in the
formation of the initial cycloadduct Va which undergoes protonation
by EtOH to form Vb (Scheme 4). Tautomerization of Vb generates
reasonably stable pyrazoline dicarboxylate intermediate 6’. However,
excess ethoxide, when present in the medium, acts as a nucleophile
and causes decarboxylation and detosylation of 6 furnishing 5’ which
readily tautomerizes to 5 via a 1,3-proton shift.
Table 3. Scope of arylidenemalonates with Cs2CO3 as basea
Scheme 4. Proposed mechanism for the formation of pyrazole from
diazosulfone and arylidenemalonates
After investigating the scope of Cs2CO3 mediated synthesis of
pyrazole carboxylates 5, we subjected various arylidenemalonates 4 to
study the effect of substituents on the ratio of the products 5 and 6
when sodium ethoxide was used as the base (Table 4).
Arylidenemalonate 4b, bearing a weakly electron donating substituent
such as methyl at the para position, afforded a mixture of pyrazole 5b
in 50% yield and pyrazoline 6b in 39% yield (entry 2). However, a
strongly electron rich aryl derivative 4c furnished only the pyrazoline
dicarboxylate 6c, that too in moderate yield (40%, entry 3). In the case
of deactivated aryl derivatives 4d and 4f, pyrazolines 6d and 6f,
respectively, were the only products which were formed in
Entry
1
2
3
4
5
6
7
R
C6H5
Time/h
4
4
3
2
2
1.5
4
1.5
12
16
% Yieldb
70
4
5
4a
4b
4c
4d
4e
4f
4g
4h
4i
5a
5b
5c
5d
5e
5f
5g
5h
5i
4-MeC6H4
4-OMeC6H4
4-ClC6H4
4-FC6H4
4-CNC6H4
4-NO2C6H4
1-naphthyl
2-furyl
58
40c
d
-
60
56
e
-
8
9
10
32c
comparable
yields
(62-63%,
entries
4-5).
Finally,
58f
naphthylidenemalonate 4h provided a mixture of pyrazole 5h (10%
yield) and pyrazoline 6h (52% yield, entry 6).
The structures of pyrazole carboxylate 5 and the intermediate
pyrazoline dicarboxylate 6 were unambiguously confirmed by single
crystal X-Ray diffraction analysis of representative compounds 5a and
6h.
g
C6H5-CH=CH
-
4j
5j
a Reaction scale: arylidenemalonate 4 (0.5 mmol), diazosulfone 2 (0.6
mmol, 1.2 equiv), Cs2CO3 (0.75 mmol, 1.5 equiv), EtOH (5 mL).
b After silica gel column chromatography.
c No characterizable side products were observed in these reactions.
d 6d was isolated in 63% yield.
Table 4. Scope of arylidenemalonates 4 with NaOEt as basea
Entry
Ar
Time/h
% Yield/5b
% Yield/ 6b
4
5
6
1
2
3
4
5
6
C6H5
2.5
3.5
4
1.5
1.5
1.5
34
50
38c
39
4a
4b
4c
4d
4f
5a
5b
5c
5d
5f
6a
6b
6c
6d
6f
4-MeC6H4
4-OMeC6H4
4-ClC6H4
4-CNC6H4
1-naphthyl
d
-
-
-
40e
63
d
d
62
52
10
4h
5h
6h
a Reaction scale: arylidenemalonate 4 (0.5 mmol), diazosulfone 2 (0.6 mmol, 1.2 equiv), NaOEt (0.6 mmol, 1.2 equiv), EtOH (5 mL).
bAfter silica gel column chromatography.
c Could not be isolated in pure form as it decomposed during attempted purification.
d Not observed.
e No characterizable side products were observed in this reaction.

5
ACCEPTED MANUSCRIPT
Table 5. Scope of 1,3-dicarbonyl derivativesa
Entry
Time (h)
% Yieldb
7
Product
Figure 1. X-ray structures of 5a and 6h
It may be noted that pyrazoline dicarboxylates 6c, 6d and 6f were
formed as the only products and could be isolated in pure form before
they underwent elimination to the corresponding pyrazole
carboxylates 5c, 5d and 5f (Table 4). Subsequently, these pyrazoline
dicarboxylates (6c, 6d and 6f) and crude 6a were subjected to
microwave irradiation under mild basic conditions (0.5 equiv Cs2CO3)
to achieve their complete conversion to the respective pyrazole
carboxylates 5a, 5c, 5d and 5f in nearly quantitative yield (96-97%,
Scheme 5).
Scheme 5. Conversion of pyrazoline dicarboxylates to pyrazole
carboxylates
To further extend the scope of our diazosulfone cycloaddition, other
benzylidene-1,3-dicarbonyls 7a-d were prepared and their
cycloaddition with diazosulfone 2 was investigated (Table 5).
Although the optimized conditions (Cs2CO3, EtOH, 0º C) worked
reasonably well for malonates 4 for the selective synthesis of pyrazole
carboxylates 5, these conditions were not suitable for arylidene-1,3-
dicarbonyls 7a-d as intractable mixtures of pyrazoline and pyrazole
were often formed. Therefore, NaOEt (1.5 equiv) was used as the base
to achieve best results. Benzylidenediketones 7a and 7b afforded
acylated pyrazoles 8a and 3a, respectively, in 62% and 75% yields
(entries 1-2). Ketoester 7c, the condensation product of benzaldehyde
and ethylacetoacetate, reacted with sulfone 2 and provided pyrazole
carboxylate 5a as the only product in 70% yield (entry 3). The above
observations confirmed that deacylation could also take place under
our experimental conditions (entries 2-3) and it is in fact preferred
over decarboxylation (entry 3). A cyclic malonate equivalent 7d, the
condensation product of Meldrum’s acid and an aromatic aldehyde,
afforded pyrazole carboxylate 5k in 50% yield (entry 4).
a Reaction scale: 7 (0.5 mmol), diazosulfone 2 (0.6 mmol, 1.2 equiv),
NaOEt (0.75 mmol, 1.5 equiv), EtOH (5 mL); intractable mixtures of
pyrazoline and pyrazole derivatives were often formed in the presence
of Cs2CO3 in EtOH at 0º C.
b After silica gel column chromatography.
4. Experimental section
4.1 General Experimental Details
1
The melting points recorded are uncorrected. NMR spectra (1H, H
decoupled 13C) were recorded with TMS as the internal standard. The
coupling constants (J values) are given in Hz. High resolution mass
spectra were recorded under ESI Q-TOF conditions. X-ray data were
collected on a diffractometer equipped with graphite monochromated
Mo Kα radiation. The structure was solved by direct methods
shelxs97 and refined by full-matrix least squares against F2 using
shelxl97 software. Chalcones,19 arylidenemalonates,20 α-diazo-β-
ketosulfone21 and compounds 7a-d22 were prepared following the
literature procedures.
3. Conclusions
Synthesis of 3-acyl and 3-carboxyl substituted pyrazoles via 1,3-
dipolar cycloaddition of chalcones, arylidenemalonates and other
arylidene-1,3-dicarbonyls with a diazosulfone, generated in situ from
α-diazo-β-ketosulfone, has been carried out. The diazosulfonyl anion
intermediate was generated from α-diazo-β-ketosulfone in the
presence of Cs2CO3 or NaOEt in EtOH. While in the case of
chalcones, cycloaddition followed by detosylation takes place to
provide 3-aroyl pyrazoles,18 a decarboxylation or deacylation takes
place prior to detosylation in the initial cycloadduct arising from
arylidene-1,3-dicarbonyls. This protocol also highlights the role of
diazosulfone as a safe and easy-to-handle diazomethane equivalent in
the synthesis of pyrazole derivatives. The dual role of NaOEt as a
nucleophile and as a base is also reflected in our reaction.
4.2 General procedure for synthesis of pyrazoles 3 from chalcones 1
and sulfone 2 (see Table 1)
To a solution of chalcone 1 (0.5 mmol) in dry EtOH (5 mL), was
added diazosulfone 2 (238 mg, 1 mmol, 2 equiv) at RT under N2. The
reaction mixture was stirred and NaOEt (68 mg, 1 mmol, 2 equiv) in
dry EtOH (2 mL) was added. After completion of the reaction
(monitored by TLC), the reaction mixture was concentrated in vacuo
and the residue was purified by silica gel column chromatography
(EtOAc/pet ether, 2/8) to afford pure pyrazole 3.
4.2.1 Phenyl(4-phenyl)-1H-pyrazol-3-yl)(phenyl)methanone (3a)
White solid; Yield 54% (67 mg); mp 182-184 oC; IR (KBr, cm-1) 3411
(s), 2926 (s), 2852 (m), 1654 (s), 1449 (m), 1416 (m), 1344 (m), 1262
(s), 1158 (w), 911 (m), 736 (s); 1H NMR (DMSO-d6, 400 MHz) δ 7.24
(t, J = 7.3 Hz, 1H), 7.33 (t, J = 7.3 Hz, 2H), 7.44 (d, J = 7.3 Hz, 2H),

6
Tetrahedron
ACCEPTED MANUSCRIPT
7.51 (t, J = 7.2 Hz, 2H), 7.63 (t, J = 7.2 Hz, 1H), 7.97 (d, J = 7.2 Hz,
4H), 7.51-7.58 (m, 4H), 7.90 (d, J = 6.9 Hz, 2H), 12.75 (s, 1H); 13C
2H), 8.19 (s, 1H), 13.62 (brs, 1H); 13C NMR (DMSO-d6, 100 MHz) δ
123.8, 126.7, 128.2, 128.3, 128.4, 129.4, 130.2, 132.3, 132.9, 137.8,
145.8, 189.9; MS (ES+) m/z (rel intensity) 250 (MH+, 19), 249 (M+,
100), 171 (8); HRMS (ES+) calcd for C16H13N2O (MH+) 249.1028,
found 249.1033.
NMR (CDCl3, 100 MHz) δ 110.8, 118.9, 123.6, 128.6, 129.4, 130.5,
132.2, 133.7, 136.6, 137.2, 189.5; MS (ES+) m/z (rel intensity) 296
(MNa+, 24), 251 (12), 235 (100); HRMS (ES+) calcd for
C17H11N3ONa (MNa+) 296.0794, found 296.0794.
4.2.8 (4-(4-Nitrophenyl)-1H-pyrazol-3-yl)(phenyl)methanone (3h)
Off-white solid; Yield 94% (138 mg); mp 168-170 oC; IR (KBr, cm-1)
3402 (br vs), 2919 (w), 1653 (m), 1509 (w), 1336 (m), 1265 (m), 823
4.2.2 Phenyl(4-p-tolyl-1H-pyrazol-3-yl)methanone (3b)
o
Colorless solid; Yield 62% (81 mg); mp 170-172 C; IR (KBr, cm-1)
1
3400 (br vs), 3187 (s), 2962 (w), 1629 (s), 1449 (w), 1284 (w), 1251
(w), 1161 (w), 907 (m), 812 (m), 743 (m); 1H NMR (CDCl3, 400
MHz) δ 2.31 (s, 3H), 7.05 (d, J = 7.9 Hz, 2H), 7.19 (d, J = 7.9 Hz,
2H), 7.33 (t, J = 7.5 Hz, 2H), 7.49 (t, J = 7.5 Hz, 1H), 7.61 (s, 1H),
7.85 (d, J = 7.5 Hz, 2H), 11.92 (brs, 1H); 13C NMR (DMSO-d6, 100
MHz) δ 20.7, 123.8, 128.2, 128.8, 129.1, 129.3, 130.2, 132.8, 135.8,
137.8, 145.8, 189.9; MS (ES+) m/z (rel intensity) 264 (MH+, 20), 263
(M+, 100), 185 (3); HRMS (ES+) calcd for C17H15N2O(MH+)
263.1184, found 263.1184.
(w), 739 (s); H NMR (CDCl3, 400 MHz) δ 7.41 (t, J = 7.4 Hz, 2H),
7.51-7.59 (m, 3H), 7.79 (s, 1H), 7.91-7.97 (br m, 2H), 8.15 (d, J = 8.5
Hz, 2H), 11.16 (brs, 1H); 13C NMR (CDCl3, 100 MHz) δ 121.9,
123.4, 128.3, 129.2, 130.3, 130.7, 133.1, 137.4, 139.5, 145.9, 146.1,
189.5; MS (ES+) m/z (rel intensity) 295 ([M+2]+, 21), 294 (MH+,
100), 216 (7); HRMS (ES+) calcd for C16H12N3O3(MH+) 294.0879,
found 294.0878.
4.2.9 (4-(3-Nitrophenyl)-1H-pyrazol-3-yl)(phenyl) methanone (3i)
o
Light yellow solid; Yield 91% (133 mg); mp 155-157 C; IR (KBr,
4.2.3 (4-(3-Bromophenyl)-1H-pyrazol-3-yl)(phenyl)methanone (3c)
cm-1) 3400 (br vs), 2923 (vw), 1652 (vs), 1524 (w), 1450 (w), 1349
o
1
White solid; Yield 62% (101 mg); mp 166-167 C; IR (KBr, cm-1)
(m), 1254 (w), 1150 (w), 1021 (w), 910 (w), 807 (m), 735 (s); H
3271 (brm), 2930 (m), 1656 (vs), 1598 (w), 1451 (s), 1322 (s), 1248
(s), 1162 (vs), 1085 (m), 905 (s), 761 (s), 696 (s); H NMR (CDCl3,
NMR (DMSO-d6, 400 MHz) δ 7.50 (t, J = 7.0 Hz, 2H), 7.62 (t, J = 7.1
Hz, 2H), 7.92 (d, J = 7.1 Hz, 1H), 7.99 (d, J = 7.0 Hz, 2H), 8.11 (d, J
= 7.1 Hz, 1H), 8.36 (s, 1H), 8.39 (s,1H), 13.8 (brs, 1H); 13C NMR
(DMSO-d6, 100 MHz) δ 121.5, 122.0, 122.9, 128.2, 129.6, 130.3,
132.9, 134.1, 135.1, 137.6, 145.8, 147.7, 189.5; MS (ES+) m/z (rel
intensity) 295 (MH+, 14), 294 (M+, 100), 263 (42), 216 (19); HRMS
(ES+) calcd for C16H12N3O3 (MH+) 294.0879, found 294.0878.
1
400 MHz) δ 7.14-7.19 (m, 2H), 7.21-7.25 (m, 1H), 7.29-7.35 (m, 3H),
7.42-7.49 (m, 2H), 7.87 (d, J = 7.1 Hz, 2H), 13.08 (brs, 1H); 13C NMR
(CDCl3, 100 MHz) δ 121.7, 126.7, 128.3, 128.9, 129.7, 130.3, 131.3,
132.0, 133.1, 133.5, 137.3, 189.4; MS (ES+) m/z (rel intensity) 330
([M+4]+, 20), 329 ([M+3]+, 100), 328 ([M+2]+, 18), 327 (MH+, 96),
248 (5); HRMS (ES+) calcd for C16H11BrN2O(MH+) 327.0133, found
327.0128.
4.2.10 (4-Chlorophenyl)(4-phenyl-1H-pyrazol-3-yl)methanone (3j)
o
White solid; Yield 77% (109 mg); mp 155-157 C; IR (KBr, cm-1)
4.2.4 (4-(4-Chlorophenyl)-1H-pyrazol-3-yl)(phenyl)methanone (3d)
3393 (vs), 2924 (vs), 2857 (m), 1655 (vs), 1446 (w), 1262 (m), 1152
(w), 1094 (w), 1015 (w), 820 (w), 757 (m); H NMR (DMSO-d6, 400
o
1
White solid; Yield 86% (121 mg); mp 195-196 C; IR (KBr, cm-1)
3374 (br m), 2924 (s), 2857 (m), 1651 (vs), 1095 (m), 916 (s), 820
(vs), 739 (m), 693 (m); H NMR (DMSO-d6, 400 MHz) 7.36 (d, J =
MHz) δ 7.20-7.26 (m, 1H), 7.32 (t, J = 7.2 Hz, 2H), 7.43 (d, J = 7.2
Hz, 2H), 7.57 (d, J = 8.5 Hz, 2H), 7.99 (d, J = 8.5 Hz, 2H), 8.17 (s,
1H), 13.66 (brs, 1H); 13C NMR (DMSO-d6, 100 MHz) δ 124.2, 126.8,
128.2, 128.4, 128.5, 129.6, 132.1, 132.2, 136.5, 137.8, 145.5, 188.4;
MS (ES+) m/z (rel intensity) 286 ([M+4]+, 7), 285 ([M+3]+, 42), 284
([M+2]+, 21), 283 (MH+, 100), 263 (19), 171 (18); HRMS (ES+) calcd
for C16H11ClN2O(MH+) 283.0638, found 283.0635.
1
7.4 Hz, 2H), 7.44-7.50 (m, 4H), 7.60 (t, J = 6.8 Hz, 1H), 7.96 (d, J =
7.4 Hz, 2H), 8.18 (s, 1H), 13.69 (brs, 1H); 13C NMR (DMSO-d6, 100
MHz) δ 122.9, 125.8, 128.3, 128.3, 129.8, 130.3, 130.4, 131.5, 133.0,
137.8, 145.9, 189.8; MS (ES+) m/z (rel intensity) 286 ([M+4]+, 7),
285 ([M+3]+, 40), 284 ([M+2]+, 22), 283 (MH+, 100), 252 (6); HRMS
(ES+) calcd for C16H12ClN2O (MH+) 283.0638, found 283.0642.
4.2.11
(4-Chlorophenyl)(4-(4-chlorophenyl)-1H-pyrazol-3-
4.2.5 (4-(2-Chlorophenyl)-1H-pyrazol-3-yl)(phenyl)methanone (3e)
yl)methanone (3k)
o
o
Light yellow solid; Yield 94% (133 mg); mp 167-168 C; IR (KBr,
White solid; Yield 70% (111 mg); mp 165-167 C; IR (KBr, cm-1)
cm-1) 3122 (br s), 2915 (s), 1655 (vs), 1597 (m), 1345 (m), 1273 (m),
3110 (s), 2912 (s), 1654 (vs), 1588 (m), 1427 (s), 1342 (m), 1095 (s),
918 (m), 817 (m); H NMR (DMSO-d6, 400 MHz) δ 7.35 (d, J = 7.9
1
1
740 (m), 693 (m); H NMR (CDCl3, 400 MHz) δ 7.11 (t, J = 7.8 Hz,
1H), 7.23 (d, J = 7.8 Hz, 1H), 7.33-7.39 (m, 3H), 7.45 (s, 1H), 7.51-
7.56 (m, 2H), 7.87 (d, J = 7.5Hz, 2H), 12.06 (brs, 1H); 13C NMR
(CDCl3, 100 MHz) δ 122.4, 123.8, 127.7, 128.4, 128.6, 129.9, 130.3,
130.4, 131.1, 131.8, 133.4, 133.8, 137.5, 189.8; MS (ES+) m/z (rel
intensity) 286 ([M+4]+, 7), 285 ([M+3]+, 40), 284 ([M+2]+, 22), 283
(MH+, 100); HRMS (ES+) calcd for C16H11ClN2O(MNa+) 305.0452,
found 305.0453.
Hz, 2H), 7.46 (d, J = 7.7 Hz, 2H), 7.54 (d, J = 7.9 Hz, 2H), 7.98 (d, J
= 7.7 Hz, 2H), 8.17 (s, 1H), 13.74 (brs, 1H); 13C NMR (DMSO-d6,
100 MHz) δ 123.1, 128.2, 128.5, 130.0, 130.4, 131.2, 131.6, 132.2,
136.4, 138.0, 145.5, 188.3; MS (ES+) m/z (rel intensity) 321 ([M+5]+,
12), 319 ([M+3]+, 65), 317 (MH+, 100), 282 (8); HRMS (ES+) calcd
for C16H11Cl2N2O(MH+) 317.0248, found 317.0238.
4.2.12
(4-Chlorophenyl)(4-(3-nitrophenyl)-1H-pyrazol-3-
4.2.6 (4-(4-Fluorophenyl)-1H-pyrazol-3-yl)(phenyl)methanone (3f)
White solid; Yield 95% (126 mg); mp 140-141 oC;IR (KBr, cm-1)
3394 (br vs), 2891 (w), 1652 (vs), 1551 (w), 1398 (w), 1342 (m), 1158
(m), 914 (m), 821 (s), 740 (s); 1H NMR (DMSO-d6, 400 MHz) δ 7.13-
7.17 (m, 2H), 7.45-7.65 (m, 5H), 7.96 (d, J = 6.6 Hz, 2H), 8.17 (s,
1H), 13.62 (brs, 1H); 13C NMR (DMSO-d6, 100 MHz) δ 114.9 (d, JC-F
= 22.0 Hz), 123.0, 128.2, 128.7, 129.5, 130.3, 130.4 (d, J = 8.0 Hz),
132.8, 137.8, 145.7, 161.2 (d, JC-F = 241.0 Hz), 189.6; MS (ES+) m/z
(rel intensity) 268 ([M+2]+, 24), 267 (MH+, 100); 19F NMR (CDCl3,
470 MHz) δ -114.81; HRMS (ES+) calcd for C16H12FN2O(MH+)
267.0934, found 267.0948.
yl)methanone (3l)
o
Light yellow solid; Yield 88% (144 mg); mp 171-173 C; IR (KBr,
cm-1) 3075 (m), 2802 (w), 1658 (w), 1516 (m), 1554 (w), 1517 (m),
1
1405 (m), 1350 (vs), 1083 (m), 741 (vs); H NMR (DMSO-d6, 400
MHz) δ 7.59 (d, J = 8.4 Hz, 2H), 7.64 (t, J = 7.5 Hz, 1H), 7.93 (d, J =
7.5 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H), 8.12 (d, J = 7.5 Hz, 1H), 8.38 (s,
1H), 8.39 (s, 1H), 13.86 (s, 1H); 13C NMR (DMSO-d6, 100 MHz) δ
121.7, 122.2, 123.1, 128.4, 129.7, 130.8, 132.3, 134.1, 135.3, 136.3,
137.9, 145.5, 147.8, 188.0; MS (ES+) m/z (rel intensity) 350 (MNa+,
100), 328 (MH+, 20), 235 (13); HRMS (ES+) calcd for
C16H10ClN3O3Na (MNa+) 350.0303, found 350.0304.
4.2.7 4-(3-Benzoyl-1H-pyrazol-4-yl)benzonitrile (3g)
o
White solid; Yield 93% (127 mg); mp 143-145 C; IR (KBr, cm-1)
3445 (br m), 2923 (s), 2225 (m), 1654 (vs), 1611 (m), 125 (m), 1093
1
(s), 1013 (s), 829 (m); H NMR (CDCl3, 400 MHz) δ 7.38-7.42 (m,

7
4.3 General procedure for the synthesis of pyrazoles 5 from
arylidenemalonates 4 and sulfone 2 (see Table 3)
(rel intensity) 264 (MNa+, 100), 161 (6); HRMS (ES+) calcd for
C13H11N3O2Na (MNa+) 264.0743, found 264.0744.
ACCEPTED MANUSCRIPT
To a stirred solution of arylidenemalonate 4 (0.5 mmol) and α-diazo-
β-ketosulfone 2 (143 mg, 0.6 mmol, 1.2 equiv) in dry EtOH (5 mL)
was added Cs2CO3 (245 mg, 0.75 mmol, 1.5 equiv) at 0 C and the
resulting mixture was stirred until the reaction was complete
(monitored by TLC). Then the reaction mixture was concentrated in
vacuo and the crude residue was directly subjected to silica gel
column chromatography (pet ether/ethyl acetate: 8/2) to afford pure
pyrazole carboxylate 5.
4.3.6 Ethyl 4-(naphthalen-1-yl)-1H-pyrazole-5-carboxylate (5h)
White solid, Yield 32% (42 mg); mp 142 oC; IR (KBr, cm-1) 3407 (br
vs), 3230 (br vs), 2986 (w), 1689 (vs), 1475 (m), 1430 (m), 1353 (m),
1283 (s), 1182 (m), 1013 (m), 775 (m); 1H NMR (500 MHz, CDCl3) δ
0.70 (t, J = 7.1 Hz, 3H), 4.01 (q, J = 7.1 Hz, 2H), 7.39-7.51 (m, 4H),
7.73 (d, J = 8.4 Hz, 1H), 7.88 (t, J = 8.4 Hz, 2H), 7.91 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 13.5, 60.8, 122.7, 125.1, 125.8, 126.0,
126.2, 128.1, 128.2, 128.3, 128.6, 129.6, 130.5, 133.1, 133.6, 162.2;
MS (ES+) m/z (rel intensity) 305 (MK+, 100), 289 (MNa+, 55);
HRMS (ES+) calcd for C16H14N2O2K (MK+) 305.0687, found
305.0689.
o
4.3.1 Ethyl 4-phenyl-1H-pyrazole-3-carboxylate (5a)
White solid, Yield 50% (54 mg); mp 156 oC; IR (KBr, cm-1) 3230 (br
vs), 2986 (w), 2926 (w), 1685 (vs), 1434 (m), 1289 (m), 1269 (m),
1174 (m), 759 (m); 1H NMR (400 MHz, CDCl3) δ 1.28 (t, J = 7.1 Hz,
3H), 4.36 (q, J = 7.1 Hz, 2H), 7.32-7.45 (m, 3H), 7.52-7.54 (m, 2H),
7.86 (s, 1H), 9.47 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.3,
61.3, 125.5, 127.6, 128.1, 129.7, 131.9, 134.9, 135.6, 161.7; MS
(ES+) m/z (rel intensity) 239 (MNa+, 100); HRMS (ES+) calcd for
C12H12N2O2Na (MNa+) 239.0791, found 239.0790 Selected
crystallographic parameters for C12H12N2O2, M = 216.24, Monoclinic,
space group P2(1)/n, a = 12.343(9) Å, b = 7.749(5) Å, c =
12.3545(10) Å, α = 90°, β = 114.9500°, γ = 90°, V = 1071.4(10) Å3,
Dc = 1.341 Mg/m3, Z = 4, F(000) = 456, λ = 0.71073 Å, µ = 0.093
mm-1, Total unique reflections = 8004 / 1955 [R(int) = 0.0921], T =
100(2) K, θ range = 3.07 to 25.33°, Final R indices [I>2σ(I)] : R1 =
0.0447, wR2 = 0.0893, R(all data) : R1 = 0.0667, wR2 = 0.0981.
4.3.7 Ethyl 4-(furan-2-yl)-1H-pyrazole-3-carboxylate (5i)
White solid, Yield 58% (60 mg); mp 142 oC; IR (KBr, cm-1) 3122 (w),
2981 (w), 2923 (m), 1718 (vs), 1446 (m), 1356 (w), 1286 (s), 1171
(m), 1033 (m), 743 (w); 1H NMR (500 MHz, CDCl3) δ 1.45 (t, J = 7.2
Hz, 3H), 4.50 (q, J = 7.2 Hz, 2H), 6.49 (dd, J = 3.3, 1.7 Hz, 1H), 7.09
(d, J = 3.3 Hz, 1H), 7.45 (t, J = 1.7 Hz, 1H), 8.12 (s, 1H); 13C NMR
(125 MHz, CDCl3) δ 14.5, 61.5, 109.5, 111.6, 115.9, 127.3, 129.8,
132.2, 135.0, 141.6, 146.4, 161.6; MS (ES+) m/z (rel intensity) 229
(MNa+, 100); HRMS (ES+) calcd for C10H10N2O3Na (MNa+)
229.0584, found 229.0584.
4.4 General procedure for the synthesis of pyrazolines 6 from
arylidenemalonates 4 and sulfone 2 (see Table 4)
4.3.2 Ethyl 4-p-tolyl-1H-pyrazole-3-carboxylate (5b)
To a stirred solution of arylidenemalonate 4 (0.5 mmol, 1 equiv) and
α-diazo-β-ketosulfone 2 (143 mg, 0.6 mmol, 1.2 equiv) in dry EtOH
(5 mL) was added NaOEt (41 mg, 0.6 mmol, 1.2 equiv) at 0 C and
the resulting mixture was stirred until the reaction was complete
(monitored by TLC) keeping the temperature maintained at 0 oC. Then
the reaction mixture was concentrated in vacuo and the crude residue
was directly subjected to silica gel column chromatography (pet
ether/ethyl acetate: 8/2) to afford pure pyrazolines 6.
White solid, Yield 58% (67 mg); mp 208 oC; IR (KBr, cm-1) 3235 (br
m), 3128 (w), 2930 (w), 1687 (vs), 1436 (m), 1296 (s), 1280 (s), 1248
(m), 1178 (m), 1171 (m), 1020 (m), 832 (s); 1H NMR (400 MHz,
CDCl3) δ 1.32 (t, J = 7.2 Hz, 3H), 2.38 (s, 3H), 4.36 (q, J = 7.2 Hz,
2H), 7.21 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.72 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 14.3, 21.4, 61.4, 127.5, 128.3, 128.5,
129.0, 129.4, 129.9, 137.6, 160.8; MS (ES+) m/z (rel intensity) 253
(MNa+, 100); HRMS (ES+) calcd for C13H14N2O2Na (MNa+)
253.0947, found 253.0944.
o
4.4.1 Diethyl 4-(p-tolyl)-3-tosyl-1H-pyrazole-5,5(4H)-dicarboxylate
(6b)
4.3.3 Ethyl 4-(4-methoxyphenyl)-1H-pyrazole-3-carboxylate (5c)
White solid, Yield 40% (49 mg); mp 162 oC; IR (KBr, cm-1) 3246 (br
s), 3128 (w), 2985 (m), 2836 (w), 1722 (m), 1688 (m), 1442 (m), 1273
White solid; Yield 39% (90 mg); mp 102 oC IR (KBr, cm-1) 3336 (s),
2983 (m), 1741 (s), 1515 (w), 1447 (w), 1329 (m), 1274 (s), 1220 (m),
1113 (m), 812 (m); 1H NMR (400 MHz, CDCl3) δ 0.74 (t, J = 7.1 Hz,
3H), 1.23 (t, J = 7.1 Hz, 3H), 2.25 (s, 3H), 2.36 (s, 3H), 3.62- 3.67 (m,
1H), 3.72- 3.79 (m, 1H), 4.18- 4.36 (m, 2H), 5.23 (s, 1H), 6.89 (bs,
2H), 7.04 (d, J = 7.3 Hz, 2H), 7.12 (d, J = 8.1 Hz, 2H), 7.17 (s, 1H),
7.45 (d, J = 8.1 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.4, 14.1,
21.3, 21.8, 56.1, 62.6, 63.5, 81.3, 128.5, 129.2, 129.6, 136.8, 138.4,
144.8, 153.8, 165.5, 167.2; MS (ES+) m/z (rel intensity) 481 (MNa+,
100); HRMS (ES+) calcd for C23H26N2O6S (MNa+) 481.1404, found
481.1407.
1
(s), 1249 (vs), 1179 (vs), 1162 (vs), 1020 (m), 832 (m), 816 (m); H
NMR (500 MHz, CDCl3) δ 1.32 (t, J = 7.2 Hz, 3H), 3.85 (s, 3H), 4.36
(q, J = 7.2 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 7.49 (d, J = 8.7 Hz, 2H),
7.69 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.3, 55.5, 61.3, 113.6,
124.1, 125.5, 129.1, 130.8, 135.1, 159.3, 161.5; MS (ES+) m/z (rel
intensity) 269 (MNa+, 100), 247 (MH+, 3); HRMS (ES+) calcd for
C13H14N2O3Na (MNa+) 269.0897, found 269.0896.
4.3.4 Ethyl 4-(4-fluorophenyl)-1H-pyrazole-3-carboxylate (5e)
White solid, Yield 60% (70 mg); mp 176 oC; IR (KBr, cm-1) 3223 (br
s), 2923 (m), 1686 (vs), 1436 (s), 1289 (s), 1267 (m), 1173 (m), 1015
4.4.2 Diethyl 4-(4-methoxyphenyl)-3-tosyl-1H-pyrazole-5,5(4H)-
dicarboxylate (6c)
1
(m), 831 (s); H NMR (400 MHz, CDCl3) δ 1.19 (t, J = 7.1 Hz, 3H),
Viscous liquid; Yield 40% (97 mg); IR (KBr, cm-1) 3330 (m), 2982
(m), 1741 (vs), 1610 (m), 1596 (w), 1514 (s), 1329 (s), 1253 (vs),
4.22 (q, J = 7.1 Hz, 2H), 7.02 (t, J = 8.7 Hz, 2H), 7.37-7.42 (m, 2H),
7.61 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 14.3, 61.4, 115.1 (d, JC-F
= 24.5 Hz), 124.9, 127.7, 131.3 (d, JC-F = 7.5 Hz), 134.1, 136.4, 161.2
(d, J = 245.0 Hz), 163.8; 19F NMR (CDCl3, 376 MHz) δ -114.75; MS
(ES+) m/z (rel intensity) 257 (MNa+, 100), 244 (10); HRMS (ES+)
calcd for C12H11FN2O2Na (MNa+) 257.0697, found 257.0686.
1
1220 (m), 1147 (m), 1114 (m), 1033 (m), 755 (m), 670 (s); H NMR
(400 MHz, CDCl3) δ 0.77 (t, J = 7.2 Hz, 3H), 1.26 (t, J = 7.2 Hz, 3H),
2.36 (s, 3H), 3.59-3.67 (m, 1H), 3.73 (s, 3H), 3.74-3.83 (m, 1H), 4.19-
4.34 (m, 2H), 5.25 (s, 1H), 6.61 (d, J = 8.4 Hz, 2H), 6.88-6.90
(unresolved m, 2H), 7.04 (s, 1H), 7.12 (d, J = 8.3 Hz, 2H), 7.47 (d, J
= 8.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 13.5, 14.1, 21.7, 55.4,
55.8, 62.6, 63.5, 81.2, 113.9, 124.6, 128.5, 129.6, 130.5, 136.8, 144.8,
153.7, 159.8, 165.5, 167.2; HRMS (ES+) calcd for C23H26N2O7SNa
(MNa+) 497.1353, found 497.1358.
4.3.5 Ethyl 4-(4-cyanophenyl)-1H-pyrazole-3-carboxylate (5f)
White solid, Yield 56% (67 mg); mp 144 oC; IR (KBr, cm-1) 3419 (br
vs), 2991 (w), 2225 (m), 1719 (s), 1691 (s), 1607 (s), 1441 (m), 1355
1
(m), 1285 (s), 1161 (m), 828 (s); H NMR (500 MHz, CDCl3) δ 1.31
(t, J = 7.2 Hz, 3H), 4.35 (q, J = 7.2 Hz, 2H), 7.66, 7.69 (ABq, J = 8.4
Hz, 4H), 7.77 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 14.3, 61.7,
111.4, 119.0, 123.9, 130.3, 132.0, 135.6, 136.8, 161.0; MS (ES+) m/z
4.4.3
Diethyl
4-(4-chlorophenyl)-3-tosyl-1H-pyrazole-5,5(4H)-
dicarboxylate (6d)
White solid; Yield 63% (150 mg); mp 110 C; IR (KBr, cm-1) 3338
o
(w), 2982 (w), 1742 (vs), 1683 (m), 1491 (m), 1331 (m), 1303 (m),

8
Tetrahedron
1281 (s), 1148 (m), 1091 (s), 1016 (m), 814 (m), 666 (m), 592 (m);
ACCEPTED MANUSCRIPT
1H NMR (400 MHz, CDCl3) δ 0.74 (t, J = 7.1 Hz, 3H), 1.23 (t, J = 7.1
Hz, 3H), 2.36 (s, 3H), 3.60-3.67 (m, 1H), 3.73- 3.79 (m, 1H), 4.18-
4.30 (m, 2H), 5.23 (s, 1H), 6.87-6.92 (br unresolved d, 2H), 7.03 (d, J
= 7.3 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 7.17 (brs, 1H), 7.44 (d, J = 8.1
Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 13.4, 13.9, 21.7, 55.5, 62.7,
63.6, 81.1, 128.3, 128.6, 129.7, 130.5, 131.2, 134.6, 136.4, 145.1,
152.1, 165.1, 166.8; MS (ES+) m/z (rel intensity) 503 ([M+2]Na+,
40), 501 (MNa+, 100); HRMS (ES+) calcd for C22H23ClN2O6SNa
(MNa+) 501.0858, found 501.0862.
4.5.3 Ethyl 4-(4-chlorophenyl)-1H-pyrazole-3-carboxylate (5d)
White solid, Yield 97% (24 mg); mp 142 oC; IR (KBr, cm-1) 3339 (br
m), 2988 (w), 1742 (vs), 1492 (m), 1445 (m), 1332 (m), 1274 (s),
1
1219 (m), 1149 (m), 1091 (s), 1017 (m), 737 (m), 665 (s); H NMR
(500 MHz, CDCl3) δ 1.37 (t, J = 7.1 Hz, 3H), 4.41 (q, J = 7.1 Hz,
2H), 7.40-7.42 (m, 2H), 7.44-7.51 (m, 2H), 7.90 (s, 1H); 13C NMR
(125 MHz, CDCl3) δ 14.0, 60.3, 122.7, 125.5, 127.9, 128.1, 130.8,
131.7, 140.1, 162.6; MS (ES+) m/z (rel intensity) 275 ([M+2]Na+,
30), 273 (MNa+, 100), 251 (MH+, 10), 235 (35); HRMS (ES+) calcd
for C12H11ClN2O2Na (MNa+) 273.0401, found 273.0403.
4.4.4
Diethyl 4-(4-cyanophenyl)-3-tosyl-1H-pyrazole-5,5(4H)-
dicarboxylate (6f)
4.5.4 Ethyl 4-(4-cyanophenyl)-1H-pyrazole-3-carboxylate (5f)
1
White solid; Yield 62% (164 mg); mp 110 oC ; IR (KBr, cm-1) 3317
(m), 2985 (m), 2230 (s), 1742 (s), 1596 (w), 1447 (w), 1330 (m),
White solid, Yield 96% (23 mg); mp, IR, H, 13C and Mass data are
consistent with those of 5f obtained from 4f (Table 3).
1
1275 (m), 1149 (m), 669 (s); H NMR (400 MHz, CDCl3) δ 0.73 (t,
J = 7.2 Hz, 3H), 1.21 (t, J = 7.1 Hz, 3H), 2.35 (s, 3H), 3.56- 3.63
(m, 1H), 3.71- 3.78 (m, 1H), 4.18- 4.31 (m, 2H), 5.27 (s, 1H), 7.13
(d, J = 7.9 Hz, 2H), 7.38 (d, J = 7.9 Hz, 3H), 7.46 (d, 8.1 Hz, 2H),
7.62 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 13.4, 13.8, 21.6, 55.7,
62.7, 63.7, 81.2, 112.2, 118.1, 128.2, 129.7, 129.9, 130.0, 131.8,
132.1, 136.1, 138.2, 145.4, 151.7, 164.8, 166.4; MS (ES+) m/z (rel
intensity) 492 (MNa+, 100); HRMS (ES+) calcd for C23H23N3O6S
(MNa+) 492.1200, found 492.1196.
4.6 General procedure for the reaction of arylidene-1,3-dicarbonyls 7
with sulfone 2 (see Table 5)
To a stirred solution of 7 (0.5 mmol, 1 equiv) and α-diazo-β-
ketosulfone 2 (143 mg, 0.6 mmol, 1.2 equiv) in dry EtOH (5 mL) was
added NaOEt (51 mg, 0.75 mmol, 1.5 equiv) at 0 oC and the resulting
mixture was stirred at the same temperature until the reaction was
complete (monitored by TLC). Then the reaction mixture was
concentrated in vacuo and the crude residue was directly subjected to
silica gel column chromatography (pet ether/ethyl acetate: 8/2) to
afford pure 3, 5 or 8.
4.4.5 Diethyl 4-(naphthalen-1-yl)-3-tosyl-1H-pyrazole-5,5(4H)-
dicarboxylate (6h)
o
White solid; Yield 52% (137 mg); mp 140 C; IR (KBr, cm-1) 3338
(m), 1739 (s), 1596 (w), 1329 (s), 1272 (s), 1148 (m), 799 (m), 672
(s); 1H NMR (400 MHz, CDCl3) δ 0.14 (t, J = 7.2 Hz, 3H), 1.29 (t, J
= 7.2 Hz, 3H), 2.36 (s, 3H), 3.12- 3.17 (m, 1H), 3.38- 3.44 (m, 1H),
4.27- 4.36 (m, 2H), 6.27 (s, 1H), 6.76-6.78 (dd, J = 1.1 Hz, 7.2 Hz,
1H),7.00- 7.04 (m, 2H), 7.05 (s, 1H) 7.37-7.39 (dd J = 1.6 Hz, 6.9
Hz, 2H), 7.48-7.52 (td, J = 0.9, 7.0 Hz, 1H); 7.58-7.62 (td, J = 1.3,
6.9 Hz, 1H), 7.68 (d, J = 8.3 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 8.3
(d, J = 8.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 12.7, 14.1, 21.7,
62.4, 63.6, 81.5, 123.9, 125.0, 126.1, 127.0, 127.5, 128.1, 128.5,
128.7, 128.8, 128.9, 129.0, 129.6, 132.0, 133.8, 136.6, 145.0, 154.0,
165.5, 167.5; HRMS (ES+) calcd for C26H26N2O6S (MNa+)
517.1404, found 517.1397. Selected crystallographic parameters for
C26H26N2O6S, M = 494.56, Monoclinic, space group P 1 21/c 1, a =
11.140(4) Å, b = 13.845(5) Å, c = 15.887(5) Å, α = 90°, β =
95.476°, γ = 90°, V = 2439.1(15) Å3, Dc = 1.347Mg/m3, Z = 4,
F(000) = 1040, λ = 0.71070 Å, µ = 0.177 mm-1, Total unique
reflections = 32157 / 6542 [R(int) = 0.1780], T = 100(2) K, θ range
= 3.21 to 29.16°, Final R indices [I>2σ(I)] : R1 = 0.0711, wR2 =
0.1531, R(all data) : R1 = 0.1225, wR2 = 0.1863.
4.6.1 Phenyl(4-phenyl-1H-pyrazol-3-yl)methanone (3a)
1
White solid; Yield 75% (117 mg); mp, IR, H, 13C and Mass data are
consistent with those of 3a obtained from 1a (Table 1).
4.6.2 Ethyl 4-phenyl-1H-pyrazole-3-carboxylate (5a)
1
White solid, Yield 70% (76 mg); mp, IR, H, 13C and Mass data are
consistent with those of 5a obtained from 4a (Table 3).
4.6.3 Ethyl 4-(3,4-dimethoxyphenyl)-1H-pyrazole-3-carboxylate (5k)
o
White solid; Yield 50% (69 mg); mp 157 C; IR (KBr, cm-1) 3214
(brs), 2960 (w), 1685 (vs), 1513 (m), 1465 (s), 1438 (m), 1327 (m),
1
1253 (s), 1182 (m), 1146 (s), 1027 (m), 851 (m); H NMR (500 MHz,
CDCl3) δ 1.31 (t, J = 7.2 Hz, 3H), 3.91 (s, 6H), 4.36 (q, J = 7.2 Hz,
2H), 6.90 (d, J = 8.2 Hz, 1H), 7.10 (d, J = 8.2 Hz, 1H), 7.14 (s, 1H),
7.76 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 14.4, 56.1 (× 2), 61.3,
110.9, 113.2, 122.0, 124.5, 125.6, 134.6, 135.8, 148.5, 148.8, 161.4;
MS (ES+) m/z (rel intensity) 299 (MNa+, 40), 277 (MH+, 42), 232
(15), 231 (100); HRMS (ES+) calcd for C14H16N2O4Na (MNa+)
299.1008, found 299.0997.
4.5 General procedure for the synthesis of pyrazole carboxylate 5
from pyrazoline 6 under MW irradiation (see Scheme 5)
4.6.4 1-(4-Phenyl-1H-pyrazol-3-yl)ethanone (8a)
White solid; Yield 62% (58 mg); mp 151 oC; IR (KBr, cm-1) 3228 (s),
2998 (w), 2343 (w), 1673 (s), 1454 (m), 1424 (m), 1115 (m), 1095
1
In a 10 mL microwave glass vial containing EtOH (1 mL), was
added pyrazoline 6 (0.1 mmol) followed by Cs2CO3 (16.5 mg, 0.05
mmol, 0.5 equiv) and the resulting mixture was subjected to
microwave irradiation for 10-15 min at 80 oC until the completion of
reaction (monitored by TLC). After removal of EtOH in vacuo, the
residue was treated with water (10 mL) and the aqueous layer was
extracted with EtOAc (2 × 10 mL). The combined organic layer was
dried over anhydrous Na2SO4, filtered and the filtrate was then
concentrated in vacuo. The residue was recrystallized from
EtOAc/hexane (1:1) to obtain pure 5 in quantitative yields.
(m), 950 (m); H NMR (500 MHz, CDCl3) δ 2.44 (s, 3H), 7.34-7.39
(m, 2H), 7.41-7.45 (m, 3H), 7.66 (s, 1H), 9.47 (br s, 1H); 13C NMR
(100 MHz, CDCl3) δ 28.5, 125.3, 128.0, 128.1, 128.5, 129.7, 132.1,
135.4, 192.6; MS (ES+) m/z (rel intensity) 371 ([2M-1]+, 28), 355
([2M-17]+, 100), 333 (10); HRMS (ES+) calcd for C11H10N2O (MNa+)
209.0685, found 209.0682.
Acknowledgments
INNN thanks SERB, DST India for financial assistance and DN
thanks UGC India for a senior research fellowship. The authors thank
Dr. Rahul Kumar for carrying out preliminary work in this project.
4.5.1 Ethyl 4-phenyl-1H-pyrazole-3-carboxylate (5a)
1
White solid, Yield 96% (21 mg); mp, IR, H, 13C and Mass data are
consistent with those of 5a obtained from 4a (Table 3).
References and notes
1. Selected books/reviews: (a) Elguero, J. In Comprehensive Heterocyclic
Chemistry; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.,
Pergamon: Oxford, 1996; Vol. 3, pp 1. (b) Dolzhenko, A. V.;
Dolzhenko, A. V.; Chui, W. K. Heterocycles 2008, 75, 1575-1622. (c)
Dadiboyena S.; Nefzi, A. Eur. J. Med. Chem. 2011, 46, 5258-5275. (d)
4.5.2 Ethyl 4-(4-methoxyphenyl)-1H-pyrazole-3-carboxylate (5c)
1
White solid, Yield 97% (24 mg); mp, IR, H, 13C and Mass data are
consistent with those of 5c obtained from 4c (Table 3).

9
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ACCEPTED MANUSCRIPT
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come across a work similar to that described in Table 1 having
recently appeared: Ahamad, S.; Patidar, R. K.; Kumar, A.; Kant, R.;
Mohanan, K. ChemistrySelect 2017, 2, 11995-11998. The authors
reported a three-component reaction of aldehyde, β-ketophosphonate
and diazosulfone.
19. Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R.
Vogel’s Text Book of Practical Organic Chemistry, Addison Wesley
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Mahendran,
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