A novel and simple route for the synthesis of 3,4-disubstituted pyrroles

Article abstract of DOI:10.1002/jhet.5570420226

A new class of 3,4-disubstituted pyrroles has been prepared by the reaction of 1-aroyl-2-arylsulfonylethenes and 1,2-diarylsulfonylethenes with tosyl methyl isocyanide.

Full text of DOI:10.1002/jhet.5570420226

March 2005
333
A Novel and Simple Route for the Synthesis of
3,4-Disubstituted Pyrroles
Venkatapuram Padmavathi*, Boggu Jagan Mohan Reddy and Adivireddy Padmaja
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India
Received June 14, 2004
A new class of 3,4-disubstituted pyrroles has been prepared by the reaction of 1-aroyl-2-arylsul-
fonylethenes and 1,2-diarylsulfonylethenes with tosyl methyl isocyanide.
J. Heterocyclic Chem., 42, 333 (2005).
Introduction.
knowledge there are no reports of the synthesis of 3,4-dis-
ubstituted pyrroles from α,β-unsaturated sulfones. In a
preliminary communication, we have recently reported the
synthesis of 3,4-disubstituted pyrroles by cyclocondensa-
tion of aryl styryl sulfones and benzyl styryl sulfones with
tosyl methyl isocyanide. On the other hand, phenyl vinyl
sulfones under similar conditions produced 3- and 3,5-dis-
ubstituted pyrroles [16].
In continuation of our studies for the preparation of 3,4-
disubstituted pyrroles we wish to report the use of different
Michael acceptors for the efficient conversion into pyrroles,
using TosMIC. Recently we have reported the synthesis of
Michael acceptors, unsaturated oxo sulfones and bis sul-
fones by the reaction between vinyl chloride and aroyl/aryl
sulfonyl chloride under Friedel Craft's reaction conditions
[17]. These activated unsaturated systems have been used as
Pyrroles are of pharmacological relevance due to their
antiinflammatory and analgesic activities. The prominent
examples are ketorolac, tolmetin and indomethacin [1]. In
view of the importance of these compounds substantial
attention has been paid to their synthesis, which proceeds
mainly via cycloaddition or cycloisomerization of acyclic
precursors [2-5]. Besides, the conjugate addition of nucle-
ophiles to α,β-unsaturated compounds is one of the most
powerful bond forming strategies and has been widely uti-
lized in the field of heterocyclic chemistry. The Barton-
Zard pyrrole synthesis based on the reaction of nitro
alkenes with ethyl isocyanate also provides an ideal
method for β-substituted pyrroles [6-12]. Tosyl methyl iso-
cyanide (TosMIC) has also been used as a reagent for the
synthesis of pyrroles [13-15]. However, to the best of our

334
V. Padmavathi, B. Jagan Mohan Reddy and A. Padmaja
Vol. 42
1
13
1
dipolarophiles and condensed with various 1,3-dipolar
reagents to get a variety of heterocycles [18,19].
structure is confirmed by H and C NMR spectra. The H
NMR spectrum of 11a displayed singlets at δ 7.06 and
7.06 for C -H and C -H where as in the C NMR spec-
H
13
In our present approach, the synthesis of 3,4-disubsti-
tuted pyrroles is envisaged by a simple and common route
using these Michael acceptors. When 1-benzoyl-2-aryl sul-
fonyl ethene (4) is treated with TosMIC (5) in the presence
of sodium hydride in a mixture of ether and DMSO, 3-ben-
zoyl-4-arylsulfonyl-1H-pyrrole (6) is obtained (Scheme
2
5
trum signals are observed at 119.6, 110.9, 110.9 and 119.6
for C , C , C and C (Table 2).
In summary we have developed an effective and simple
route for the synthesis of 3,4-disubstituted pyrroles from
1-benzoyl-2-arylsulfonylethene and 1,2-diarylsulfonyl-
ethene using TosMIC.
2
3
4
5
1
and Table 1). The H NMR spectrum of 6a showed two sin-
13
glets at δ 8.05 and 7.09 for C -H and C -H. The C NMR
H
2
5
spectrum of 6a displayed signals at 139.6, 118.7, 109.8 and
120.9 for C , C , C and C , respectively apart from signals
EXPERIMENTAL
2
3
4
5
due to carbonyl and aromatic carbons (Table 2). Similar
reaction of 1,2-diarylsulfonylethene (10) with TosMIC (5)
resulted in 3,4-bisarylsulfonyl-1H-pyrrole (11), whose
Melting points were determined on a Mel-Temp apparatus and
are uncorrected. IR spectra (KBr disc) were recorded on
Beckmann IR-18 spectrophotometer. H NMR spectra were
1
Table 1
Physical Properties and IR data of Compounds 6 and 11
-1
Compd.
m.p.
( C)
Yield
(%)
Mol. Formula
(Mol.Wt.)
Calcd. (Found) (%)
H
IR (cm )
C=O C=C NH
o
C
N
SO
2
6a
128-129
132-134
149-151
142-144
198-200
221-223
216-218
234-236
52.3
68.4
72.3
75.6
55.2
64.6
63.8
67.6
C
C
H
NO S
65.58
(65.52)
63.33
(63.37)
59.05
(59.10)
53.70
(53.66)
55.32
(55.28)
54.10
(54.22)
50.33
(50.31)
46.16
(46.12)
4.21
(4.26)
4.43
(4.39)
3.50
(3.53)
2.92
(2.95)
3.77
(3.79)
4.01
(4.08)
3.17
(3.14)
2.66
(2.64)
4.50
(4.57)
4.10
(4.17)
4.05
(4.11)
3.68
(3.74)
4.03
(4.07)
3.71
(3.64)
3.67
(3.73)
3.36
(3.41)
1134
1320
1128
1342
1120
1324
1148
1306
1142
1318
1128
1324
1132
1341
1146
1325
1658 1589 3378
1664 1593 3365
1654 1589 3378
1650 1596 3391
17 13
3
(311.36)
NO S
6b
H
18 15
4
(341.38)
C H ClNO S
17 12
(345.80)
C H Cl NO S
17 11
6c
3
6d
2
3
(380.25)
NO S
11a
11b
11c
11d
C
H
-
-
1596 3368
1589 3354
1594 3358
1598 3385
16 13
4
2
(347.41)
NO S
C
H
17 15
5
2
(377.44)
ClNO S
4 2
C
H
-
16 12
(381.86)
Cl NO S
4 2
(416.30)
C
H
-
16 11
2
Table 2
Spectroscopic Data of Compounds of 6 and 11
1
13
Compd.
6a
H NMR (δ, ppm)
C NMR (δ, ppm)
7.09 (s, 1H, C -H), 7.15-7.89 (m, 10H, Ar-H), 8.05 (s,
109.8 (C ), 118.7 (C ), 120.9 (C ), 139.6 (C ), 188.5 (C=O), 126.8, 128.5,
4 3 5 2
5
1H, C -H), 10.39 (bs, 1H, NH)
129.7, 130.5, 132.6, 133.4, 133.6, 138.9 (Aromatic carbons)
56.2 (OCH ), 110.9 (C ), 116.8 (C ), 120.7 (C ), 141.6 (C ), 188.2 (C=O),
2
6b
3.75 (s, 3H, OCH ), 7.08 (s, 1H, C -H), 7.15-7.89 (m,
3 5
3
4
3
5
2
9H, Ar-H), 8.09 (s, 1H, C -H), 10.52 (bs, 1H, NH)
115.4, 127.7, 128.8, 130.1, 131.2, 132.8, 133.6, 167.5 (Aromatic carbons)
110.6 (C ), 117.9 (C ), 121.3 (C ), 140.7 (C ), 188.4 (C=O), 128.4, 128.9,
2
6c
7.11 (s, 1H, C -H), 7.25-8.01 (m, 9H, Ar-H), 8.14 (s,
5
4
3
5
2
1H, C -H), 10.52 (bs, 1H, NH)
130.4, 131.0, 133.9, 132.6, 136.7, 139.5 (Aromatic carbons)
110.4 (C ), 121.8 (C ), 127.3 (C ), 141.9 (C ), 188.3 (C=O), 128.3, 129.1,
2
6d
7.13 (s, 1H, C -H), 7.26-7.99 (m, 8H, Ar-H), 8.12 (s,
5
4
3
5
2
1H, C -H), 10.55 (bs, 1H, NH)
129.8, 130.6, 131.3, 132.4, 133.0, 135.4, 137.4, 138.3 (Aromatic carbons)
110.9 (C & C ), 119.6 (C & C ), 126.8, 129.7, 133.9, 138.6
2
11a
11b
11c
11d
7.06 (s, 2H, C -H & C -H), 7.30-7.93 (m, 10H,
2 5
3
4
2
5
Ar-H), 10.38 (bs, 1H, NH)
3.76 (s, 3H, OCH ), 7.10 (s, 2H, C -H & C -H), 7.30-
(Aromatic carbons)
56.2 (OCH ), 111.5 (C & C ), 120.6 (C & C ), 115.4, 126.6, 127.8, 129.7,
3
2
5
3
3
4
2
5
7.93 (m, 9H, Ar-H), 10.41 (bs, 1H, NH)
7.12 (s, 2H, C -H & C -H), 7.30-7.93 (m, 9H,
130.9, 134.0, 139.0, 167.4 (Aromatic carbons)
111.3 (C & C ), 121.4 (C & C ), 126.7, 127.8, 129.6, 130.0, 134.1, 136.9,
2
5
3
4
2
5
Ar-H), 10.39 (bs, 1 H, NH)
7.09 (s, 2H, C -H & C -H), 7.12-7.93 (m, 8H
139.2, 139.9 (Aromatic carbons)
112.4 (C & C ), 121.8 (C & C ), 126.5, 126.8, 128.9, 130.4, 131.5, 133.8,
2
5
3
4
2
5
Ar-H), 10.44 (bs, 1 H, NH)
135.6, 138.5, 139.2, 140.0 (Aromatic carbons)

March 2005
Communication to the Editor
335
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3
13
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2
room temperature. The reaction mixture is stirred for 24 hours
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2
phase dried over anhydrous Na SO . Concentration of the sol-
2
4
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2
layer is dried over anhydrous Na SO . Concentration of the sol-
2
4
vent gave crude product, which is purified by filtration through a
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REFERENCES AND NOTES
*
To whom correspondence should be addressed: Email: vkpu-
ram2001@yahoo.com