E,E-bis(styryl)sulfones-synthons for a new class of bis(heterocycles)

Article abstract of DOI:10.1002/jhet.332

(Chemical Equation Presented) A new class of bis heterocycles having two different heterocyclic rings viz., pyrroles in combination with pyrazolines and isoxazolines were synthesized. All the compounds were characterized by elemental and spectral analysis.

Full text of DOI:10.1002/jhet.332

July 2010
E,E-Bis(Styryl)Sulfones—Synthons for a New Class of
Bis(heterocycles)
825
Venkatapuram Padmavathi,* Boggu Jagan Mohan Reddy, Konda Mahesh,
Pinnu Thriveni, and Adivireddy Padmaja
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India
*E-mail: vkpuram2001@yahoo.com
Received July 26, 2009
DOI 10.1002/jhet.332
Published online 4 June 2010 in Wiley InterScience (www.interscience.wiley.com).
A new class of bis heterocycles having two different heterocyclic rings viz., pyrroles in combination
with pyrazolines and isoxazolines were synthesized. All the compounds were characterized by elemental
and spectral analysis.
J. Heterocyclic Chem., 47, 825 (2010).
INTRODUCTION
were often complicated and limited to only some sub-
stituents. Previously, 3,4-disubstituted pyrroles were
synthesized from Michael acceptors and tosylmethyl iso-
cyanide (TosMIC) [5]. Following this synthetic method-
ology, we have reported recently a new regioselective
one step procedure using phenyl vinyl sulfone, aryl sty-
ryl sulfones, benzyl styryl sulfones and TosMIC, leading
to a series of 3,4-disubstituted pyrroles in good yields
[6]. Similarly, pyrazolines and isoxazolines were pre-
pared by 1,3-dipolar cycloaddition of an ylide to an
alkene involving the 3þ2 cycloaddition principle [7].
Among the ylides, diazomethane, nitrile imines, and
nitrile oxides were used extensively as reactive inter-
mediates. These nitrile imines and nitrile oxides can be
generated by the dehydrogenation of araldehyde phenyl-
hydrazones and araldoximes with lead tetraacetate [8],
mercury acetate [9], 1-chlorobenzotriazole [10], chlor-
amine-T [11] etc. Use of the latter for in situ generation
of dipolar reagents has enthused many organic chemists.
In fact, we have reported the 1,3-dipolar cycloaddition
reaction of Chloramine-T catalysed dipolar reagents
with variety of activated mono and bis(olefins) [12].
Apart from these, bis heterocycles, bis pyrroles and pyr-
rolyl pyrazoles were prepared from 1-arylsulfonyl-2-
styrylsulfonyl ethenes by 1,3-dipolar cycloaddition
methodology [13]. The present communication deals
with the synthesis of hitherto unknown sulfonelinked bis
(heterocycles) having pyrrole together with pyrazole or
Heterocyclic chemistry has attracted a lot of interest
during recent years as many useful drugs have emerged
in this branch. In fact, the development of simple, facile,
and efficient synthetic methodologies for the develop-
ment of five membered heterocycles has been a chal-
lenging task in organic synthesis. Amongst five mem-
bered heterocycles, pyrroles, pyrazoles, and isoxazoles
have gained importance because of their varied physio-
logical activities. As constituents of cytotoxic drugs,
such as netrospin and distamycin, 4-aminopyrrole-2-car-
boxylates, have been used as the main compounds in
the construction of a diverse series of DNA-binding
ligands exhibiting antibiotic, antiviral, and oncolytic
properties [1]. The related 3-amino pyrroles also exhibit
anticonvulsant activity by blocking sodium channels [2].
In addition, pyrazolines and isoxazolines have gained
importance due to their various chemotherapeutic prop-
erties. In fact, Celecoxib, a pyrazole derivative and Val-
decoxib, an isoxazole derivative, have been widely used
in the market as anti-inflammatory drugs [3]. Hence, it
was considered worthwhile to prepare molecules having
both pyrrole and pyrazole/isoxazole rings. In the litera-
ture, 3,4-disubstituted pyrroles were reported either by
coupling imines and nitroalkanes or by using Friedel-
Craft’s acylation in the presence of an electron-with-
drawing group on the pyrrole nitrogen or on 3,4-sily-
lated precursors [4]. However, these synthetic routes
C
V
2010 HeteroCorporation

826
V. Padmavathi, B. J. Mohan Reddy, K. Mahesh, P. Thriveni, and A. Padmaja
Vol 47
Scheme 1
isoxazole units, from 1,3-dipolar cycloaddition of Tos-
MIC, nitrile imines and nitrile oxides to sulfonyl acti-
vated olefins.
as 4-aryl-3-(20-arylethenesulfonyl)-1H-pyrrole (2) by
spectral studies (Scheme 1; Table 1). Compound 2a
exhibited two singlets at d 6.85 and 7.48 ppm, assigned
to C2-H and C5-H of pyrrole ring protons. Two doublets
were observed at d 6.96 and 7.63 ppm corresponding to
olefinic protons, in addition to the signals of aromatic
protons (Table 3). The 13C nuclear mass spectroscopy
(NMR) spectra of 2a showed signals at d 119.8, 125.7,
125.9, and 127.3 for pyrrole ring carbons, C-4, C-3, C-
5, C-2 and at d 124.2, 141.3 ppm for olefinic carbons,
C-10, C-20 (Table 3). Thus the formation of 2 indicates
that the reaction was regiospecific. Attempts to prepare
bis (4-aryl-1H-pyrrol-3-yl)sulfone (3) by treating 1 with
RESULTS AND DISCUSSION
The synthetic scheme was based on the reactivity of
E,E-bis(styryl)sulfone (1) towards 1,3-dipolar reagents
viz., TosMIC, diazomethane, nitrile imines and nitrile
oxides. When 1 was treated with TosMIC in the pres-
ence of sodium hydride in a mixture of ether and dime-
thylsulfoxide, a solid was obtained which was identified
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2010
E,E-Bis(Styryl)Sulfones—Synthons for a New Class of Bis(heterocycles)
827
Table 1
Physical and analytical data of compounds 2–9.
Analysis % calculated/
found
Compound
Mp (ꢀC)
221–223
Yield (%)
72
Ar
Ar’
–
Molecular formula
C
H
N
2a
C6H5
C18H15NO2S (309.40)
69.88
69.80
65.02
64.92
57.15
57.08
68.94
68.85
64.69
64.76
57.56
57.50
64.94
65.00
61.29
61.37
54.29
54.20
73.93
74.00
70.32
70.43
69.20
69.27
61.34
61.25
70.07
70.14
66.38
66.32
64.86
64.78
56.46
56.52
65.31
65.26
74.23
74.33
70.40
70.52
4.89
4.94
5.18
5.24
3.46
3.44
4.63
4.68
4.93
4.96
3.38
3.35
4.87
4.92
5.14
5.20
3.60
3.58
5.00
5.06
5.18
5.14
4.49
4.53
3.65
3.69
4.70
4.68
4.95
5.00
4.14
4.10
3.22
3.18
4.33
4.31
4.62
4.67
4.25
4.28
4.53
4.50
3.79
3.85
3.70
3.67
8.04
8.11
6.86
6.92
6.71
6.66
11.96
12.05
10.21
10.33
9.99
10.08
8.34
8.27
7.45
7.38
7.81
7.92
6.92
7.00
6.54
6.60
5.73
5.67
6.05
6.13
5.27
5.22
12.02
12.12
8.38
8.46
6.57
6.51
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
5d
6a
6b
6c
6d
7a
8a
9a
243–245
265–267
232–234
225–227
270–272
242–244
230–232
256–258
282–284
270–272
288–290
296–298
277–278
264–266
252–254
280–282
274–276
296–298
287–289
69
66
76
80
82
68
70
65
68
64
71
65
70
65
68
72
66
65
68
4-OMeC6H4
4-ClC6H4
C6H5
–
C20H19NO4S (369.45)
C18H13Cl2NO2S (378.29)
C20H16N2O2S (348.43)
C22H20N2O4S (408.48)
C20H14Cl2N2O2S (417.32)
C19H17N3O2S (351.43)
C21H21N3O4S (411.49)
C19H15Cl2N3O2S (420.33)
C31H25N3O2S (503.63)
C33H29N3O4S (563.68)
C31H24ClN3O2S (538.07)
C31H22Cl3N3O2S (606.96)
C25H20N2O3S (428.52)
C27H24N2O5S (488.57)
C25H19ClN2O3S (462.96)
C25H17Cl3N2O3S (531.85)
C19H15N3O2S (349.42)
C31H23N3O2S (501.61)
C25H18N2O3S (426.50)
–
–
4-OMeC6H4
4-ClC6H4
C6H5
–
–
–
4-OMeC6H4
4-ClC6H4
C6H5
–
–
C6H5
C6H5
4-ClC6H4
4-ClC6H4
C6H5
C6H5
4-ClC6H4
4-ClC6H4
-
4-OMeC6H4
C6H5
4-ClC6H4
C6H5
4-OMeC6H4
C6H5
4-ClC6H4
C6H5
C6H5
C6H5
C6H5
C6H5
two equivalents of TosMIC were not successful. How-
ever, 3 was obtained by treating 2 with one equivalent
of TosMIC, as confirmed by NMR spectroscopy. Com-
pound 3a exhibited two sharp singlets at d 6.84 and
the pyrazoline ring protons at d 4.48 (HA), 3.86 (HM) and
3.48 ppm (HX) respectively, in addition to the signals of
the pyrrole ring protons. The observed coupling constant
values JAM ¼ 12.6, JAX ¼ 5.5 and JMX ¼ 10.0 Hz indi-
cated that HA and HM were cis, HA and HX were trans
and HM and HX were geminal. The 13C NMR spectrum
of 4a exhibited signals at d 46.9, 57.2, 119.4, 120.3,
124.8, 125.6 and 152.3 ppm for the carbons C-40, C-50,
C-4, C-3, C-5, C-2, and C-30, respectively (Table 2).
In addition, the reaction of 2 with nitrile imines and
nitrile oxides generated from araldehyde phenylhydra-
zones and araldoximes in the presence of chloramine-T
resulted in (10,30,50-triaryl-40,50-dihydro-10H-pyrazol-40-
yl)-(4-aryl-1H-pyrrol-3-yl)-sulfones (5) and (30,50-diaryl-
7.08 ppm corresponding to C2,2 -H and C5,5 -H. The 13C
NMR spectra of 3a exhibited signals at 119.2 (C-4,40),
122.6 (C-3,30), 126.2 (C-5,50), 127.4 (C-2,20). This indi-
cates that the molecule was highly symmetrical.
0
0
The olefin in 2 was utilized in the synthesis of pyrazo-
lines and isoxazolines. When 2 was subjected to 1,3-dipo-
lar cycloaddition reaction with diazomethane, (40-aryl-
40,50-dihydro-10H-pyrazol-30-yl)-(4-aryl-1H-pyrrol-3-yl)-
1
sulfone (4) was obtained (Scheme 1; Table 1). The H
NMR spectra of 4a showed an AMX splitting pattern of
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

828
V. Padmavathi, B. J. Mohan Reddy, K. Mahesh, P. Thriveni, and A. Padmaja
Vol 47
Table 2
gel H, BDH, ethyl acetate-hexane, 1:3). The infrared (IR)
spectra were recorded on a Thermo Nicolet IR 200 FT-IR in
KBr pellets and the wave numbers were given in cmꢁ1. The
1H NMR spectra were recorded in CDCl3/DMSO-d6 on a Jeol
JNM k-300 MHz. The 13C NMR spectra were recorded in
CDCl3/DMSO-d6 on a Jeol JNM spectrometer operating at
75.5 MHz. All chemical shifts are reported in d (ppm) using
TMS as an internal standard. Elemental analyses were per-
formed using Perkin-Elmer 240C elemental analyser. The start-
ing substrates E,E-bis(styryl)sulfones were prepared according
to the literature procedure [14]. Araldehyde phenylhydrazones
and araldoximes were prepared by standard procedures [15].
Infrared data of compounds 2–9.
IR (KBr) cmꢁ1
Compound
SO2
C¼C
C¼N
NH
2a
2b
2c
3a
3b
3c
4a
4b
4c
5a
5b
5c
5d
6a
6b
6c
6d
7a
7b
7c
1130, 1300
1145, 1297
1132, 1295
1140, 1294
1128, 1305
1124, 1296
1125, 1325
1132, 1320
1128, 1325
1126, 1295
1130, 1292
1132, 1304
1125, 1310
1140, 1305
1135, 1315
1124, 1296
1132, 1315
1120, 1300
1124, 1298
1128, 1310
1635
1632
–
–
3175
3170
3180
3182
3168
3172
3185
3180
3190
3195
3188
3178
3182
3200
3205
3210
3205
3198
3186
3198
1630
–
–
–
–
–
–
–
–
1570
1575
1572
1558
1568
1560
1562
1574
1562
1578
1566
1573
1558
1574
4-Aryl-3-(2-arylethenesulfonyl)-1H-pyrroles (2).
Gen-
–
–
eral procedure. A mixture of TosMIC (5 mmol) and 1 (5
mmol) in Et2O/DMSO (2:1) was added dropwise under stirring
to a suspension of NaH (50 mg) in Et2O (10 mL) at room tem-
perature. Stirring was continued for about 6 h. Then it was
diluted with H2O and extracted with Et2O. The ethereal layer
was dried over anhydrous Na2SO4. The solvent was removed
in vacuo. The resultant solid was purified by recrystallization
from MeOH.
–
–
–
–
–
–
–
–
Bis(4-aryl-1H-pyrrol-3yl)-sulfones
(3).
General
1625
1628
1630
procedure. A mixture of TosMIC (5 mmol) and 2 (5 mmol) in
Et2O/DMSO (2:1) was added dropwise under stirring to a sus-
pension of NaH (50 mg) in Et2O (10 mL) at room tempera-
ture. Stirring was continued for about 7 h. Then, H2O was
added and the product was extracted with Et2O and dried over
anhydrous Na2SO4. The solvent was removed in vacuo. The
resultant solid was purified by column chromatography [Silica
gel, hexane-ethyl acetate (1:4)].
(40-Aryl-40,50-dihydro-10H-pyrazol-30-yl)-(4-aryl-1H-pyr-
rol-3-yl)-sulfones (4). General procedure. To a cooled so-
lution of 2 (5 mmol) in CH2Cl2 (20 mL), an ethereal solution
of diazomethane (40 mL, 0.4M) and triethylamine (0.12 g) were
added. The reaction mixture was kept at ꢁ20 to ꢁ15ꢀC for 48–
56 h. The solvent was removed under reduced pressure. The re-
sultant solid was purified by recrystallization from MeOH.
(10,30,50-Triaryl-40,50-dihydro-10H-pyrazol-40-yl)-(4-aryl-
40,50-dihydroisoxazol-40-yl)-(4-aryl-1H-pyrrol-3-yl)-sulfone
(6), respectively (Scheme 1; Table 1). The H NMR spec-
trum of 5a and 6a displayed two doublets at d 5.25, 5.19
and 5.63, 5.67 ppm, respectively, which were assigned to
1
0
0
C4 -H and C5 -H, the two methine protons of the pyrazo-
line and isoxazoline rings. The J values indicated that
they were in trans geometry (Table 3). The 13C NMR
spectra of 5a and 6a displayed signals at 63.0, 64.9 (C-
40), 87.4, 83.7 (C-50), 119.2, 119.4 (C-4), 121.0, 121.9 (C-
3), 124.4, 124.3 (C-5), 126.8, 126.3 (C-2) and 154.9,
151.7 (C-30), respectively (Table 3). Compounds 4a, 5a
and 6a on oxidation with chloranil in xylene, gave the
corresponding pyrazoles and isoxazoles 7a, 8a and 9a.
The disappearance of two doublets corresponding to pyra-
zoline/isoxazoline ring protons in the 1H NMR spectra
confirmed their formation.
1H-pyrrol-3-yl)-sulfones (5).
General procedure. A mix-
ture of 2 (1 mmol), araldehyde phenylhydrazone (2 mmol) and
chloramine-T (2 mmol) in MeOH (20 mL) was refluxed for
20–22 h. over a water bath. The precipitated inorganic salts
were filtered off. The filtrate was concentrated and the residue
was extracted with CH2Cl2. The organic phase was washed
with water, brine and dried over anhydrous Na2SO4. The sol-
vent was removed under reduced pressure. Recrystallization of
the crude product from ethanol resulted in pure 5.
(30,50-Diaryl-40,50-dihydro-isoxazol-40-yl)-(4-aryl-1H-pyr-
CONCLUSION
rol-3-yl)-sulfones (6).
General procedure. A mixture of 2
(1 mmol), araldoxime (2 mmol) and chloramine-T (2 mmol) in
MeOH (20 mL) was refluxed for 16–18 h. over a water bath.
The precipitated inorganic salts were filtered off. The filtrate
was concentrated and the residue was extracted with CH2Cl2.
The organic phase was washed with water, brine and dried
over anhydrous Na2SO4. The solvent was removed under
reduced pressure. Recrystallization of the crude product from
ethanol resulted in pure 6.
A
simple dipolarophile, bis(styryl)sulfone was
exploited to get a new and novel sulfone-linked bis(he-
terocycles) containing two different heterocyclic rings
adopting simple and versatile 1,3-dipolar cycloaddition
methodology.
(40-Phenyl-10H-pyrazol-30-yl)-(4-phenyl-1H-pyrrol-3-yl)-
sulfone (7a)/(4-phenyl-1H-pyrrol-3-yl)-(10,30,50-triphenyl-10H-
pyrazol-40-yl)-sulfone (8a)/(30,50-diphenyl-isoxazol-40-yl)-(4-
phenyl-1H-pyrrol-3-yl)-sulfone (9a). General procedure. A
solution of 4a/5a/6a (1 mmol) and chloranil (1.04 mmol) in
EXPERIMENTAL
Melting points were determined in open capillaries on a
Mel-Temp apparatus and are uncorrected. The purity of the
compounds was checked by thin layer chromatography (Silica
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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E,E-Bis(Styryl)Sulfones—Synthons for a New Class of Bis(heterocycles)
829
Table 3
1H and 13C NMR data of compounds 2–9.
Compound
1H NMR (CDCl3/DMSO-d6) d, ppm
13C NMR (CDCl3/DMSO-d6) d, ppm
0
2a
6.85 (s, 1H, C2-H), 6.96 (d, 1H, C1 -H, J ¼ 15.6 Hz), 7.48
119.8 (C-4), 124.2 (C-10), 125.7 (C-3), 125.9 (C-5), 127.3
0
(s, 1H, C5-H), 7.15-7.62 (m, 10H, Ar-H), 7.63 (d, 1H, C2 -H,
J ¼ 15.6 Hz), 9.04 (bs, 1H, NH)
(C-2), 141.3 (C-20)
0
2b
2c
3.72 (s, 6H, Ar-OCH3), 6.79 (s, 1H, C2-H), 6.89 (d, 1H, C1 -
H, J ¼ 16.2 Hz), 7.41 (s, 1H, C5-H), 6.95-7.58 (m, 8H, Ar-
55.2 (Ar-OCH3), 118.7 (C-4), 123.6 (C-10), 124.9 (C-3),
125.6 (C-5), 126.8 (C-2), 140.3 (C-20)
0
H), 7.65 (d, 1H, C2 -H, J ¼ 16.2 Hz), 9.12 (bs, 1H, NH)
0
6.88 (s, 1H, C2-H), 6.89 (d, 1H, C1 -H, J ¼ 16.3 Hz), 7.45
119.6 (C-4), 124.6 (C-10), 125.8 (C-3), 126.3 (C-5), 127.6
(C-2), 140.3 (C-20)
0
(s, 1H, C5-H), 7.24-7.59 (m, 8H, Ar-H), 7.60 (d, 1H, C2 -H,
J ¼ 16.3 Hz), 9.11 (bs, 1H, NH)
0
3a
3b
3c
4a
6.84 (s, 2H, C2,2 -H), 7.08 (s, 2H, C5,50-H), 7.02-7.48 (m,
122.6 (C-3,30), 119.2 (C-4,40), 126.2 (C-5,50), 127.4
(C-2,20)
121.9 (C-3,30), 55.5 (Ar-OCH3), 118.6 (C-4,40), 125.8
(C-5,50), 127.6 (C-2,20)
122.5 (C-3,30), 120.2 (C-4,40), 124.6 (C-5,50), 127.8
(C-2,20)
46.9 (C-40), 57.2 (C-50), 119.4 (C-4), 120.3 (C-3), 124.8
(C-5), 125.6 (C-2), 152.3 (C-30)
10H, Ar-H), 9.05 (bs, 2H, NH)
3.69 (s, 6H, Ar-OCH3), 6.88 (s, 2H, C2,20-H), 7.06 (s, 2H,
C5,50-H), 6.95-7.45 (m, 8H, Ar-H), 9.12 (bs, 2H, NH)
6.89 (s, 2H, C2,20-H), 7.11 (s, 2H, C5,50-H), 7.15-7.44 (m, 8H,
Ar-H), 9.11 (bs, 2H, NH)
3.48 (dd, 1H, HX, JAX ¼ 5.5, JMX ¼ 10.0 Hz), 3.86 (t, 1H,
HM) 4.48 (dd, 1H, HA, JAM ¼ 12.6 Hz), 6.85 (s, 1H, C2-H),
7.14-7.32 (m, 10H, Ar-H), 7.74 (s, 1H, C5-H), 8.26 (bs, 1H,
NH), 10.45 (bs, 1H, NH)
4b
4c
3.46 (dd, 1H, HX, JAX ¼ 5.7, JMX ¼ 10.1 Hz), 3.67 (s, 6H,
Ar-OCH3), 3.89 (t, 1H, HM), 4.45 (dd, 1H, HA, JAM ¼ 12.8
Hz), 6.81 (s, 1H, C2-H), 7.01-7.32 (m, 8H, Ar-H), 7.73
(s, 1H, C5-H), 8.23 (bs, 1H, NH), 10.52 (bs, 1H, NH)
3.54 (dd, 1H, HX, JAX ¼ 5.7, JMX ¼ 10.2 Hz), 3.84 (t, 1H,
HM), 4.45 (dd, 1H, HA, JAM ¼ 12.9 Hz), 6.81 (s, 1H, C2-H),
7.12-7.45 (m, 8H, Ar-H), 7.69 (s, 1H, C5-H), 8.23 (bs, 1H,
NH), 10.45 (bs, 1H, NH)
46.8 (C-40), 55.3 (Ar-OCH3), 56.4 (C-50), 118.3 (C-4),
119.6 (C-3), 123.6 (C-5), 125.7 (C-2), 151.6 (C-30)
47.2 (C-40), 56.8 (C-50), 119.2 (C-4), 119.9 (C-3), 122.8
(C-5), 126.4 (C-2), 152.3(C-30)
0
0
5a
5b
5c
5d
6a
6b
6c
6d
5.25 (d, 1H, C4 -H, J ¼ 7.8 Hz), 5.63 (d, 1H, C5 -H, J ¼ 7.2
Hz), 6.79 (s, 1H, C2-H), 6.85 (s, 1H, C5-H), 7.22-7.54
(m, 20H, Ar-H), 8.85 (bs, 01H, NH)
63.6 (C-40), 87.4 (C-50), 119.2 (C-4), 121.0 (C-3), 124.4
(C-5), 126.8 (C-2), 154.9 (C-30)
3.74 (s, 6H, Ar-OCH3), 5.27 (d, 1H, C4 -H, J ¼ 6.6 Hz), 5.63
55.2 (Ar-OCH3), 64.8 (C-40), 87.3 (C-50), 120.4 (C-4),
121.6 (C-3), 123.8 (C-2), 127.2 (C-5), 154.8 (C-30)
0
(d, 1H, C5 -H, J ¼ 6.6 Hz), 6.74 (s, 1H, C2-H), 6.87 (s, 1H,
C5-H), 7.04-7.83 (m, 18H, Ar-H), 8.86 (bs, 1H, NH)
0
0
5.24 (d, 1H, C4 -H, J ¼ 6.9 Hz), 5.62 (d, 1H, C5 -H, J ¼ 6.9
Hz), 6.73 (s, 1H, C2-H), 6.85 (s, 1H, C5-H), 7.12-7.80
(m, 19H, Ar-H), 8.91 (bs, 1H, NH)
62.8 (C-40), 85.9 (C-50), 118.6 (C-4), 122.6 (C-3), 123.8
(C-2), 125.8 (C-5), 154.6 (C-30)
0
0
5.26 (d, 1H, C4 -H, J ¼ 6.4 Hz), 5.65 (d, 1H, C5 -H, J ¼ 6.4
Hz), 6.76 (s, 1H, C2-H), 6.92 (s, 1H, C5-H), 7.18-7.82
(m, 17H, Ar-H), 8.93 (bs, 1H, NH)
63.9 (C-40), 84.6 (C-50), 119.3 (C-4), 121.8 (C-3), 124.6
(C-2), 124.9 (C-5), 153.7 (C-30)
0
0
5.19 (d, 1H, C4 -H, J ¼ 5.9 Hz), 5.67 (d, 1H, C5 -H, J ¼ 5.9
Hz), 6.76 (s, 1H, C2-H), 6.85 (s, 1H, C5-H), 7.08-7.93
(m, 15H, Ar-H), 8.83 (bs, 01H, NH)
64.9 (C-40), 83.7 (C-50), 119.4 (C-4), 121.9 (C-3), 124.3
(C-5), 126.3 (C-2), 151.7 (C-30)
3.74 (s, 6H, Ar-OCH3), 5.21 (d, 1H, C4 -H, J ¼ 5.8 Hz), 5.66
55.6 (Ar-OCH3), 63.6 (C-40), 84.5 (C-50), 118.7 (C-4),
122.3 (C-3), 125.7 (C-5), 126.7 (C-2), 152.6 (C-30)
0
(d, 1H, C5 -H, J ¼ 5.8 Hz), 6.75 (s, 1H, C2-H), 6.87 (s, 1H,
C5-H), 7.01-7.94 (m, 13H, Ar-H), 8.86 (bs, 1H, NH)
0
0
5.23 (d, 1H, C4 -H, J ¼ 6.0 Hz), 5.72 (d, 1H, C5 -H, J ¼ 6.0
Hz), 6.74 (s, 1H, C2-H), 6.83 (s, 1H, C5-H), 7.14-7.92 (m,
14H, Ar-H), 8.91 (bs, 1H, NH)
64.6 (C-40), 83.3 (C-50), 119.8 (C-4), 122.6 (C-3), 125.5
(C-5), 126.1 (C-2), 153.8 (C-30)
0
0
5.24 (d, 1H, C4 -H, J ¼ 5.7 Hz), 5.70 (d, 1H, C5 -H, J ¼ 5.7
Hz), 6.78 (s, 1H, C2-H), 6.86 (s, 1H, C5-H), 7.18-7.89
(m, 12H, Ar-H), 8.94 (bs, 1H, NH)
64.7 (C-40), 83.9 (C-50), 119.6 (C-4), 121.8 (C-3), 125.3
(C-5), 125.9 (C-2), 152.7 (C-30)
7a
8a
9a
6.36 (bs, 1H, NH), 6.750(s, 1H, C2-H), 6.94 (s, 1H, C5-H),
6.96-7.84 (m, 11H, C5 -H & Ar-H), 8.94 (bs, 1H, NH).
6.76 (s, 1H, C2-H), 6.83 (s, 1H, C5-H), 7.10-8.02 (m, 20H,
Ar-H), 8.83 (bs, 1H, NH)
6.76 (s, 1H, C2-H), 6.86 (s, 1H, C5-H), 7.02-7.94 (m, 15H,
Ar-H), 8.92 (bs, 1H, NH)
116.8 (C-4), 122.3 (C-3), 125.8 (C-5), 127.6 (C-2), 134.7
(C-50), 140.9 (C-40), 156.8 (C-30)
118.3 (C-4), 124.6 (C-3), 125.3 (C-5), 126.5 (C-2), 144.8
(C-30), 147.8 (C-40), 150.4 (C-50)
117.3 (C-4), 122.6 (C-3), 125.6 (C-5), 127.8 (C-2), 146.3
(C-40), 147.4 (C-30), 152.5 (C-50)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

830
V. Padmavathi, B. J. Mohan Reddy, K. Mahesh, P. Thriveni, and A. Padmaja
Vol 47
[5] [a] Van Leusen, A. M.; Siderius, H.; Hoogenboom, B. E.;
Van Leusen, D. Tetrahedron Lett 1972, 13, 5337; [b] Pavri, N. P.;
Trudell, M. L. J Org Chem 1997, 62, 2649.
xylene (10 mL) was refluxed for 30–35 h. Then it was treated
with 5% sodium hydroxide solution. The organic layer was
separated and repeatedly washed with water, dried over anhy-
drous Na2SO4 and was removed on a rotary evaporator. The
solid obtained was purified by recrystallization in isopropanol
to give pure 7a/8a/9a respectively.
[6] Padmavathi, V.; Jagan Mohan Reddy, B.; Rajagopala
Sarma, M.; Thriveni, P. J Chem Res (S) 2004, 79.
[7] [a] Lee, A. G. Synthesis 1982, 508; [b] Bao-Xiang, Z.;
Yang, Y.; Shoji, E. Tetrahedron 1996, 52, 12049.
[8] Just, G.; Dahl, K. Tetrahedron 1968, 24, 5251.
Acknowledgment. The authors are thankful to DST, New Delhi,
India for the financial assistance under major research project.
[9] Lokanath Rai, K. M.; Liganna, N.; Hassner, A.; Murthy, C.
A. Org Prep Proced Int 1992, 24, 91.
[10] Khim, J. N.; Ryu, J. N. Synth Commun 1990, 20, 1373.
[11] [a] Lokanath Rai, K. M.; Hassner, A. Indian J Chem 1997,
36B, 242; [b] Lokanath Rai, K. M.; Hassner, A. Synth Commun 1997,
27, 467; [c] Hassner, A.; Lokanath Rai, K. M. Synthesis 1989, 57; [d]
Lokanath Rai, K. M.; Hassner, A. Synth Commun 1989, 19, 2799.
[12] [a] Padmavathi, V.; Bhaskar Reddy, A. V.; Sumathi, R. P.;
Bhaskar Reddy, D. Indian J Chem 1998, 37B, 1286; [b] Padmavathi,
V.; Sumathi, R. P.; Chandrasekhar Babu, N.; Bhaskar Reddy, D.
J Chem Res (S) 1999, 610; [c] Padmavathi, V.; Sumathi, R. P.; Ven-
ugopal Reddy, K.; Somasekhar Reddy, A.; Bhaskar Reddy, D. Synth
Commun 2000, 30, 4007; [d] Padmavathi, V.; Venugopal Reddy, K.;
Padmaja, A.; Bhaskar Reddy, D. Synth Commun 2002, 32, 1227; [e]
Padmavathi, V.; Venugopal Reddy, K.; Balaiah, A.; Ramana Reddy,
T. V.; Bhaskar Reddy, D. Heteroatom Chem 2002, 13, 677.
[13] Padmavathi, V.; Radha Laksmi, T.; Sudhakar Reddy, G.;
Padmaja, A. J Heterocyclic Chem 2008, 45, 1579.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet