2-Pyrazolines from 1,3-Dipolar Cycloaddition of Diazomethane to Arylsulfonylethenes

Article abstract of DOI:10.1002/jhet.5570400531

Novel 2-pyrazolines were obtained by the cycloaddition of diazomethane to bis(arylsulfonylethenyl)-sulfones (3) and 1-arylsulfonyl-2-styrylsulfonylethenes (7). Dehydrogenation of 2-pyrazolines with chloranil gave pyrazoles.

Full text of DOI:10.1002/jhet.5570400531

Sep-Oct 2003
933
2-Pyrazolines from 1,3 – Dipolar Cycloaddition of
Diazomethane to Arylsulfonylethenes
Venkatapuram Padmavathi*, Mudigonda Rajagopala Sarma,
Adivireddy Padmaja and Dandu Bhaskar Reddy
Department of chemistry, Sri Venkateswara University, Tirupati – 517502, India
Received February 19, 2003
Novel 2-pyrazolines were obtained by the cycloaddition of diazomethane to bis(arylsulfonylethenyl)-
sulfones (3) and 1-arylsulfonyl-2-styrylsulfonylethenes (7). Dehydrogenation of 2-pyrazolines with chloranil
gave pyrazoles.
J. Heterocyclic Chem., 40, 933 (2003).
Introduction.
dition of diazomethane to an olefin is a well known
process. Adopting this methodology, herein we report our
results in the reaction of sulfonyl activated bis olefinic sys-
tems with diazomethane. In fact the addition of dia-
zomethane to activated olefins results initially in 1-pyrazo-
lines which tautomerized to 2-pyrazolines as a conse-
quence of the migration of more acidic proton [3].
When bis (2-arylsulfonylethenyl)-[1,1']-sulfone (3) was
subjected to cycloaddition with diazomethane, instead of
the expected bis pyrazolines by 2+3 cycloaddition of latter
across the two double bonds, a mixture of mono- and bis-
α,β-Unsaturated sulfones are valuable intermediates in a
variety of synthetic transformations and useful as building
blocks in the synthesis of biologically active heterocycles
[1]. One such class of compounds includes pyrazole and its
derivatives, which continue to attract considerable atten-
tion in various fields because of their wide range of biolog-
ical and physical applications. In fact celecoxib which is a
pyrazole derivative is now widely used in the market as a
potential anti-inflammatory drug [2]. Though there are dif-
ferent methods for their syntheses, the 1,3-dipolar cycload-

934
V. Padmavathi, M. R. Sarma, A. Padmaja and D. B. Reddy
Vol. 40
Table 1
Physical Properties for Compounds 2-11
Compd.
mp
(°C)
Yield
(%)
Mol formula
(Molecular weight)
Calcd. (Found) %
H
C
N
2a
2b
2c
3a
3b
3c
4a
164-166
192-194
178-180
204-206
188-190
220-222
146-148
70
90
74
70
68
74
57
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
C
H
N O S
46.35
(46.51)
38.49
(38.38)
40.08
(40.19)
44.80
(44.62)
37.76
(37.88)
39.20
(39.09)
45.18
(45.32)
38.03
(38.14)
39.49
(39.35)
54.24
(54.10)
48.45
(48.32)
49.69
(49.79)
54.24
(54.12)
48.45
(48.55)
49.69
(49.50)
51. 66
(51. 78)
46.65
(46.74)
47.73
(47.84)
52.16
(52.32)
47.05
(47.17)
48.16
(48.02)
3.66
(3.54)
2.66
(2.73)
2.77
(2.63)
3.76
(3.64)
2.82
(2.74)
2.92
(2.83)
2.95
(2.89)
2.13
(2.21)
2.21
(2.16)
4.28
(4.35)
3.59
(3.51)
3.68
(3.60)
4.28
(4.32)
3.59
(3.53)
3.68
(3.61)
4.33
(4.21)
3.70
(3.62)
3.73
(3.69)
3.40
(3.36)
2.85
(2.79)
2.92
(3.00)
6.36
17 16
2
6
3
(440.53)
(6.42)
10.56
(10.48)
5.50
4b
4c
138-140
152-154
161-163
168-170
173-175
152-154
144-146
163-165
129-131
142-144
131-133
143-145
128-130
152-154
161-163
149-151
156-158
139-141
123-125
133-135
59
C
H
N O
(530.52)
C H Cl N O S
17 14
S
3
17 14
4
10
55
2
2
6
3
3
3
(509.41)
(5.38)
11.61
(11.74)
14.68
(14.79)
10.16
(10.32)
11.71
(11.84)
14.78
(14.63)
10.24
(10.37)
7.44
(7.34)
9.97
(10.04)
6.82
(6.73)
7.44
(7.36)
9.97
5a
26 63* 74**
C
H
N O S
18 18
4
6
3
(482.56)
5b
5c
25 61* 70**
C
H
N O
(572.56)
C H Cl N O S
18 16
S
3
18 16
6
10
26 68* 75**
2 4 6
(551.45)
6a
72
C
H
N O S
18 14
4
6
3
(478.53)
6b
6c
83
C
H
N O
(568.52)
C H Cl N O S
18 12
S
3
18 12
6
10
76
2 4 6
(547.42)
N O S
8a
14
C
C
H
17 16
2
4
2
2
(376.46)
N O S
8b
8c
17
H
17 15
3 6
(421.46)
C H ClN O S
17 15
(410.90)
C H N O S
17 16
(376.46)
C H N O S
17 15
(421.46)
C H ClN O S
17 15
16
2 4 2
9a
42
2
4
2
9b
9c
40
3 6
2
(10.07)
6.82
38
28 69* 73**
29 72* 75**
28 76* 79**
76
2
4
2
2
2
(410.90)
C H N O S
18 18
(6.77)
13.39
(13.14)
15.11
(15.24)
12.37
(12.20)
13.52
(13.67)
15.24
(15.36)
12.48
(12.63)
10a
10b
10c
11a
11b
11c
4
4
2
(418.50)
N O S
C
H
18 17
5 6
2
(463.49)
H ClN O S
C
18 17
4 4
(452.94)
N O S
C
H
18 14
4
4
2
(414.46)
C H N O S
18 13
(459.46)
C H ClN O S
18 13
73
5 6
2
76
4 4
(448.91)
* Yield using Method 2; ** yield using Method 3.
pyrazolines were obtained. (Scheme 1 and Table 1). They
were separated by column chromatography. The H NMR
cis, H , H are trans and H , H are geminal. Apart from
A X M X
1
this a doublet was observed at 6.65-6.68 for H while H
C D
spectra of the major product showed AMX splitting pat-
tern for pyrazoline ring protons and exhibited three double
merged with aromatic protons and appeared as a multiplet.
The coupling constant (14.2 Hz) indicates that they pos-
sess trans geometry. However, the minor one displayed
doublets in the regions 4.96-5.09 (H ), 4.42-4.49 (H ),
A
M
3.83-3.85 (H ). The coupling constant values J
=12.6,
three double doublets for H , H and H of the two pyra-
X
AM
A M X
J
= 10.1 and J = 5.5 Hz indicates that H , H are
zoline rings in the regions 4.96-5.01, 4.42-4.49 and 3.80-
MX
AX
A
M

Sep-Oct 2003
2-Pyrazolines from 1,3 – Dipolar Cycloaddition of Diazomethane
935
3.85. Infact, the highly symmetrical nature of this com-
pound is confirmed by integration. All the compounds dis-
played broad singlet around 10.22-10.30 ppm for NH pro-
tons that disappeared on deuteration. Thus they were iden-
tified as 2'-arylsulfonylethenyl-3-arylsulfonyl-2-pyra-
zolinyl-[4,1']-sulfone (4) (major) and bis (3-arylsulfonyl-
2-pyrazolinyl)-[4,4']-sulfone (5) (minor). Treatment of 4
with one more mole of diazomethane resulted in 5. The lat-
ter was also obtained directly when 3 was treated with
excess diazomethane. The reaction of 5 with chloranil in
xylene gave bis (3-arylsulfonylpyrazolyl)-[4,4']-sulfone
at 4.62-4.68, 4.10-4.16 and 3.45-3.52 which are due to
methine (H ) and methylene (H and H ) protons of
A
M
X
pyrazoline ring as in 8. Moreover, a doublet was
observed at 6.66-6.69, which accounted for H . The sig-
D
nal for H merged with that of the aromatic protons and
C
appeared as a multiplet. On the other hand 10 displayed
six sets of double doublets in the region 4.98-5.04 (H ),
A
4.45-4.53 (H ), 3.82-3.88 (H ), 4.62-4.68 (H '), 4.10-
M
X
A
4.16 (H ') 3.45-3.52 (H ') which indicated that the two
M
X
pyrazoline rings are in different environments. All the
compounds showed a broad singlet around 10.20-10.32
for NH, which disappeared on deuteration. However
treatment of 7 with two fold excess of diazomethane gave
only 10. The latter was also obtained by the treatment of
9 with diazomethane. The authenticity of 10 obtained by
1
(6) [4]. The H NMR spectrum of 6 showed a broad singlet
at 10.34 for two NH protons and a multiplet between 6.98-
7.92 for aromatic and pyrazolyl ring protons (Table 2). The
signals due to NH disappeared on deuteration.
1
Similarly, when 1-arylsulfonyl-2-styrylsulfonylethene
(7) was treated with diazomethane, instead of expected
bis pyrazolines, a mixture of mono and bis adducts were
obtained. They were separated by column chromatogra-
phy and identified as 3-arylsulfonyl-2-pyrazolinyl-4-
styrylsulfone (8), 2-arylsulfonylethenyl-4'-aryl-2'-pyra-
zolinyl-[1,3']-sulfone (9) and 3-arylsulfonyl-2-pyra-
zolinyl-4'-aryl-2'-pyrazolinyl-[4,3']-sulfone (10) by their
different routes was confirmed by TLC and H NMR
spectra. Oxidation of 10 with chloranil in xylene gave 3-
arylsulfonylpyrazolyl-4-(4'-arylpyrazolyl) sulfone (11).
1
The structure was confirmed by its H NMR spectrum,
which displayed a broad singlet at 10.32 for two NH pro-
tons and a multiplet between 6.92-7.98 for Ar-H, C -H
5
and C '-H (Table 2). The IR spectra of 4-6 and 8-11
5
showed absorption bands in the region 1575-1590 (C=N),
1
H NMR spectra (Scheme 2 and Table 1). The spectrum
1325-1360, 1125-1150 (SO ) and 3330-3350 (NH). In
2
of 8 showed AMX splitting pattern for pyrazoline ring
protons and exhibited double doublets in the regions
addition to these 4, 8 and 9 exhibited bands in the region
1610-1625 (C=C). The structures of the compounds 4-6
and 8-11 were further confirmed by C NMR spectra
13
4.98-5.04 (H ), 4.45-4.53 (H ) and 3.82-3.88 (H ). The
A
M
X
coupling constant values J
= 12.6, J = 5.5 and J
(Table 2).
AM
AX
MX
= 10.0 Hz indicates that H , H are cis, H , H are trans
In conclusion, a variety of symmetrical and unsymmet-
rical bispyrazolines were conveniently prepared by a
straightforward successfully established method, 1,3-dipo-
lar cycloaddition of dipolarophile, diazomethane to an
activated bisolefin.
A
M
A
X
and H ,H are geminal. Apart from this a doublet was
M
X
observed in the region 6.66-6.68 for H . Another proton,
C
H merged with aromatic protons and appeared as a mul-
D
tiplet. The spectrum of 9 exhibited three double doublets

936
V. Padmavathi, M. R. Sarma, A. Padmaja and D. B. Reddy
Vol. 40
Table 2
Spectroscopic Data of Compounds 4-6 and 8-11
1
13
Compd
H NMR ( δ, ppm)
C NMR ( δ ppm)
3a
3c
4a
7.28-8.05 (m, 14H, H , H & Ar-H)
147.84 (C ), 140.92 (C )
1 2
a
b
7.30-8.12 (m, 12H, H , H & Ar-H )
146.9 2(C ), 140.50 (C )
a
b
1 2
3.85 (dd, 1H, H ), 4.42 (dd, 1H, H
J
= 10.0),
52.42 (C ), 58.10 (C ), 142.14 (C ')
4 5 1
X
M
MX
5.04 (dd, 1H, H , J = 5.5, J
= 12.6), 6.68
145.13 (C '), 156.40 (C )
A
AX
AM
2 3
(d, 1H, H
J
= 14.2), 7.02-7.96 (m, 11H,
C , CD
Ar-H & H ,), 10.22 (bs, 1H, N-H)
D
4c
3.83 (dd, 1H, H ), 4.49 (dd, 1H, H
J
= 10.1),
52.29 (C ), 58.10 (C ), 142.82 (C ')
4 5 1
X
M
MX
4.96 (dd, 1H, H , J = 5.5, J
= 12.6), 6.65 (d,
145.13 (C '), 156.41 (C )
A
AX
AM
2 3
1H, H
J
= 14.2), 7.10-7.98 (m, 9H, Ar-H
C , CD
& H ,), 10.24 (bs, 1H, N-H)
D
5a
5c
3.80 (dd, 2H, H ), 4.49 (dd, 2H, H
J
= 10.0),
52.82 (C , C '), 58.60
4 4
X
M, MX
4.96 (dd, 2H, H , J = 5.5, J
= 12.6), 7.05-
(C , C '), 158.10 (C , C ′)
A
AX
AM
5 5 3 3
7.90 (m, 10H, Ar-H), 10.29 (bs, 2H, N-H)
3.85 (dd, 2H, H ), 4.42 (dd, 2H, H
J
= 10.0),
52.32 (C , C '), 59.04
4 4
X
M, MX
5.01 (dd, 2H, H , J = 5.5, J
= 12.6), 7.05-
(C , C '), 159.30 (C , C ')
A
AX
AM
5 5 3 3
7.98 (m, 8H, Ar-H), 10.29 (bs, 2H, N-H)
6.98-7.86 (m, 12H, C -H ,C '-H & Ar-H),
6a
6c
8a
135.94 (C , C '), 140.41
5 5
5
5
10.34 (bs, 2H, NH)
7.04-7.92 (m, 10H, C -H ,C '-H & Ar-H),
(C , C '), 159.10 (C ,C ')
4 4 3 3
134.92 (C , C' ), 141.25
5
5
5
5
10.30 (bs, 2H, NH)
3.82 (dd, 1H, H ), 4.45 (dd, 1H, H
(C , C '), 160.12 (C-3,C ')
4 4 3
J
= 10.0),
52.64 (C ), 58.65 (C ),
4 5
X
M
MX
5.04 (dd, 1H, H , J = 5.5, J
= 12.6), 6.68 (d,
32.58(C '), 140.32 (C '),
A
AX
AM
1 2
1H, H
J
= 14.2), 6.98- 7.82 (m, 11H, Ar-H & H ,),
158.23 (C ).
3
C , CD
D
10.20 (bs, 1H, N-H)
3.88 (dd, 1H, H ), 4.53 (dd, 1H, H
8c
J
= 10.0),
52.32 (C ), 58.05 (C ),
4 5
X
M, MX
4.98 (dd, 1H, H , J = 5.6, J
= 12.7), 6.66 (d,
132.93 (C ') 142.32 (C '),
A
AX
AM
1 2
1H, H
J
= 14.2), 7.02-7.94 (m, 10H, Ar-H
158.12 (C ).
3
C , CD
& H ,), 10.22 (bs, 1H, N-H)
D
9a
3.45 (dd, 1H, H ), 4.16 (dd, 1H, H
J
= 10.0),
52.64 (C '), 55.02 (C '),
4 5
X
M
MX
4.68 (dd, 1H, H , J = 5.6, J
= 12.7), 6.69 (d, 1
141.40 (C ), 143.53 (C ),
A
AX
AM
1 2
H, H
J
= 14.3), 7.04-7.98 (m, 11H, Ar-H
158.04 (C ').
3
D , CD
& H ,), 10.32 (bs, 1H, N-H)
C
9b
10a
3.52 (dd, 1H, H ), 4.10 (dd, 1H, H
J
= 10.0),
48.32 (C '), 55.42 (C '),
4 5
X
M, MX
4.68 (dd, 1H, H , J = 5.6, J
= 12.7), 6.66 (d,
141.10 (C ), 144.22 (C ),
A
AX
AM
1 2
1H, H
J
= 14.2), 7.06-8.01 (m, 10H, Ar-H
158.50 (C ').
3
D , CD
& H ,), 10.30 (bs, 1H, N-H)
C
3.45 (dd, 1H, H '), 3.88 (dd, 1H, H ), 4.10 (dd, 1H,
48.28 (C '), 52.38 (C ),
4 4
X
X
H
', J ' ' = 10.0), 4.45 (dd, 1H, H , J
= 10.1),
57.45 (C & C '), 157.23 (C '),
M
M X
M
MX
5 5 3
4.68 (dd, 1H, H ', J ' ' = 5.5 J ' ' = 12.6), 4.98 (dd,
158.40 (C )
3
A
A X
A M
1H, H , J = 5.4, J =12.6), 7.02-7.94 (m, 10H, Ar-H),
A
AX
AM
10.20 (bs, 2H, N-H)
10c
3.52 (dd, 1H, H '), 3.82 (dd, 1H, H ), 4.16 (dd, 1H, H ',
48.12 (C '), 52.32 (C ),
4 4
X
X
M
J
' ' = 10.0), 4.53 (dd, 1H, H , J
= 10.1), 4.62 (dd, 1H,
57.42 (C & C '), 157.20 (C '),
M X
M
MX
5 5 3
H ', J ' ' = 12.6), 5.04 (dd, 1H, H , J = 5.5, J =12.6),
158.48 (C )
3
A
A M
A
AX
AM
7.04-7.98 (m, 9H, Ar-H), 10.22 (bs, 2H, N-H)
6.92-7.85 (m, 12H, C -H, C '-H & Ar-H), 10.32 (bs, 2H, NH)
11a
11c
135.62 (C & C '), 140.62 (C '),
5 5 4
5
5
142.10 (C ), 157.23 (C '), 158.48 (C )
4
3
3
6.94-7.98 (m, 11H, C -H, C '-H & Ar-H), 10.35 (bs, 2H, NH)
135.10 (C & C '), 140.92 (C '),
5
5
5 5 4
141.18 (C ), 158.23 (C '), 159.82 (C )
4
3
3
EXPERIMENTAL
ses were performed using a Perkin-Elmer 240C elemental ana-
lyzer. The chemical shifts were measured in δ ppm. The purity of
the compounds was checked by TLC using silica gel ‘G’ (BDH)
and hexane-ethyl acetate as eluents.
1-Arylsulfonyl-2-styrylsulfonylethenes (7) were prepared as
per the literature procedure [5].
Melting points were determined on Tempo Mel-Temp appara-
tus and are uncorrected. The IR spectra were recorded on a
Perkin - Elmer grating infrared spectrophotometer model 337 as
KBr pellets and the wave numbers were given in cm . The H
NMR spectra were recorded on Bruker Spectrospin 300 MHz
-1
1
Bis(2-arylsulfonylethenyl)-[1,1']-sulfides (2).
spectrometer in CDCl with TMS as an internal standard and the
C NMR spectra were recorded on a Varian VXR spectrometer
3
13
To a solution of 10 mmoles of Na S in 20 ml of methanol, 20
2
operating at 75.5 MHz with CDCl as solvent. Elemental analy-
mmoles of 1-arylsulfonyl-2-chloroethene (1) in 20 ml of
3

Sep-Oct 2003
2-Pyrazolines from 1,3 – Dipolar Cycloaddition of Diazomethane
937
methanol was added dropwise with stirring at room temperature
for half an hour. The separated solid was collected by filtration,
washed with water and recrystallized from methanol.
added. The reaction mixture was kept at –20 to –15 °C for 48
hours. The solvent was removed under reduced pressure. The
resultant product indicated a mixture in TLC, which were sepa-
rated by column chromatography using ethyl acetate-hexane
(1:3) as eluents and identified as 3-arylsulfonyl-2-pyrazolinyl-4-
styrylsulfone (8), 2-arylsulfonylethenyl-4'-aryl-2'-pyra-
zolinyl–[1,3']-sulfone (9) and 3-arylsulfonyl-2-pyrazolinyl-4'-
aryl-2'-pyrazolinyl-[4,3']-sulfone (10).
Bis(2-arylsulfonylethenyl)-[1,1']-sulfones (3).
To a solution of 10 mmoles of 2 in 10 ml of glacial acetic acid,
35 ml of 30% H O was added in portions and refluxed for 1-2
2
2
hours. The contents were cooled and poured onto crushed ice.
The solid obtained was collected by filtration, washed with water
and dried. The crude compound was recrystallized from 2-
propanol.
Method 2.
Compound 10 was also obtained when an ethereal solution of
9 was treated with 40 ml of 4 M ethereal diazomethane and tri-
ethylamine. The work up procedure was same as above.
Cycloaddition of Diazomethane to 3.
Method 1.
Method 3.
A solution of 10 mmoles of 3 in 20 ml of dichloromethane was
cooled at ice-salt bath temperature. To this 80 ml of 4 M ethereal
solution of diazomethane and a catalytic amount of triethylamine
was added. The reaction mixture was kept at –20 to –15 °C for 48
hours. The solvent was removed under reduced pressure. The
resultant product indicated a mixture in TLC, which were sepa-
rated by column chromatography using ethyl acetate-hexane
(1:3) as eluents and identified as 2′-arylsulfonylethenyl-3-aryl-
sulfonyl-2-pyrazolinyl-[4,1']-sulfone (4) and bis(3-arylsulfonyl-
2-pyrazolinyl)-[4,4']-sulfone (5).
Compound 10 was also prepared by the treatment of 10
mmoles of 7 with 120 ml of 4 M ethereal diazomethane under
similar conditions.
Oxidation of 10.
A solution, of 5 mmoles of 10 and 5.2 mmoles of chloranil in
10 ml of xylene, was refluxed for 24-32 hours, at which time the
solution was washed with 5% NaOH solution. The organic layer
was separated and repeatedly washed with water, dried and the
solvent was removed on a rotary evaporator. The solid obtained
was purified by recrystallization in 2-propanol to get pure 3-aryl-
sulfonylpyrazolyl-4-(4'-arylpyrazolyl) sulfone (11).
Method 2.
Compound 5 was also obtained when a solution of 10 mmoles
of 4 was treated with 40 ml of 4 M ethereal diazomethane and tri-
ethylamine. The work up procedure was same as above.
Acknowledgements.
One of the authors (MRGS) wishes to thank CSIR, New Delhi,
India for the award of Senior Research Fellowship.
Method 3.
Compound 5 was also prepared by the treatment of 10 mmoles
of 3 with 120 ml of 4 M ethereal diazomethane under similar con-
ditions.
REFERENCES AND NOTES
Oxidation of 5.
[1a] R. Helder, T. Doornbos, J. Strating and B. Zwanenburg,
Tetrahedron, 29, 1375 (1973); [1b] W. E. Parham, F. D. Blake and D. R
Theissen, J. Org. Chem., 27, 2415 (1962); [1c] D. Bhaskar Reddy, A.
Padmaja, P. V. Ramana Reddy and B. Seenaiah, Sulfur Lett., 16, 227
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Padmavathi, Phosphorus, Sulfur and Silicon, 164, 23 (2000).
[2] G. Dannahardt, W. Kiefer, G. Kramer, S. Maehrlein, U. Nowe
and B. Fiebich, Eur. J. Med. Chem., 35, 499 (2000).
A solution of 5 mmoles of 5 and 5.2 mmoles of chloranil in 10
ml of xylene was refluxed for 24-32 hours at which time the solu-
tion was washed with 5% NaOH solution. The organic layer was
separated and repeatedly washed with water, dried and the sol-
vent was removed on a rotary evaporator. The product thus
obtained when recrystallized from 2-propanol furnished pure bis
(3-arylsulfonylpyrazolyl)-[4,4']-sulfone (6).
[3] D. Bhaskar Reddy, T. Seshamma and B. Venkataramana
Reddy
Cycloaddition of Diazomethane to 7.
Acta Chim. Hung., 122, 19 (1986).
[4] A. S. Shawali, H. M. Hasseneen and S. M. Sherif, J.
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[5] D. Bhaskar Reddy, N. Chandrasekhar Babu, K. Venugopal
Reddy and V. Padmavathi, Indian J. Chem., 40B, 416 (2001)
Method 1.
A solution of 10 mmoles of 7 in 20 ml of dichloromethane was
cooled at an ice-salt bath temperature. To this, 80 ml of 4 M ethe-
real diazomethane and a catalytic amount of triethylamine were