Ring and side chain formylated pyrazoles from acetophenone azines and Vilsmeier's reagent

Article abstract of DOI:10.1002/jhet.576

Differently substituted acetophenone azines on treatment with excess phosphorous oxychloride in N,N-dimethylformamide have found to yield three products in each case. An acceptable mechanism has been suggested for the formation of all the three products.

Full text of DOI:10.1002/jhet.576

May 2011
Ring and Side Chain Formylated Pyrazoles from Acetophenone
Azines and Vilsmeier’s Reagent
671
Ramaiyan Manikannan and Shanmugam Muthusubramanian*
Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai-
625 021, India
*E-mail: muthumanian2001@yahoo.com
Received May 1, 2010
DOI 10.1002/jhet.576
Published online 29 March 2011 in Wiley Online Library (wileyonlinelibrary.com).
Differently substituted acetophenone azines on treatment with excess phosphorous oxychloride in
N,N-dimethylformamide have found to yield three products in each case. An acceptable mechanism has
been suggested for the formation of all the three products.
J. Heterocyclic Chem., 48, 671 (2011).
INTRODUCTION
through column and it has been found that the reaction
has yielded three products, 2, 3, and 4 in each case
(Scheme 1), except in 1k, where only two compounds–
2k and 4k–alone could be isolated. The physical
constants and the spectral features of the respective
compounds are given in the experimental section. The
reaction has also been carried out under conventional
method in each case—by heating the above reaction
mixture at 80ꢀC for 4 to 5 h. The yields of the different
compounds 2, 3, and 4 in these cases are closer to those
obtained under microwave condition (Scheme 1).
Pyrazole derivatives, which have been the basis of
numerous dyes, also find a wide range of pharmacologi-
cal applications as analgesic, anti-inflammatory, antipy-
retic, anaesthetic, antibacterial, antimicrobial [1,2], anti-
psychotic [3], antimalarial [4], antitumor, anticancer,
antiangiogenic [5], and antianxiety activities [6,7]. Cer-
tain alkyl pyrazoles show significant bacteriostatic, bac-
tericidal, and fungicidal acitivites [8,9]. Kira et al. [10]
synthesized 1H-pyrazole-4-carbaldehyde (2) from aceto-
phenone azine using Vilsmeier’s reagent in 1:2 ratio.
It is of interest to find out the product selectivity of
the above reaction when the reaction is carried out with
excess reagent or when the microwave irradiation is
used as a source of energy. With this view, the reaction
between differently substituted acetophenone azines and
Vilsmeier’s reagent taken in excess (1:8) under the
influence of the microwave irradiation has been investi-
gated in the present work. Significant product selectivity
has been noticed and in addition to the reported product
2 by Kira et al. [10], two additional products viz 3 and
4 have been obtained in good yield. These interesting
results are summarized in this article.
Compounds 2, 3, and 4 were obtained in pure form in
all the cases and they have all been fully characterized
by spectral data. Compound 2 has been found to be 3-
aryl-1-(1-arylvinyl)-1H-pyrazole-4-carbaldehyde.
The
1H-NMR spectrum of 2b has two different methyl sig-
nals at 2.42 and 2.43 ppm as singlets accounting for
three hydrogens each. Two olefinic hydrogens appear as
singlets at 5.31 and 5.87 ppm with zero geminal cou-
pling. These two hydrogens have a common C,H-COSY
contour with the carbon at 106.7 ppm. The presence of
two aryl rings is evidenced by the signals between 7.20
to 7.80 ppm. Two singlets, one at 8.05 ppm and another
at 9.98 ppm, each accounting for one hydrogen, can be
assigned to C-5 hydrogen of the pyrazole ring and to
the hydrogen due to the formyl group at C-4 position,
respectively. The 13C-NMR spectrum and DEPT 135
spectrum of 2b is also consistent with the structure
assigned. Both the vinylic hydrogens have common
HMBC contours at 131.6 and 144.8 ppm, indicating the
former may be the ipso carbon of the aryl group and the
latter as the olefinic quaternary carbon. Of the signals
RESULTS AND DISCUSSION
Differently substituted acetophenone azines were pre-
pared by the reaction of hydrazine and substituted aceto-
phenone [11–16]. These azines (1) were then treated
with phosphorous oxychloride in 1:8 ratio taken in
dimethylformamide under microwave irradiation for 30
to 60 seconds. The products obtained were separated
C
V
2011 HeteroCorporation

672
R. Manikannan and S. Muthusubramanian
Vol 48
Scheme 1
blets at 6.69 ppm (J ¼ 2.7 Hz, 1H) and 7.32 ppm (J ¼
2.7 Hz, 1H) have connecting contours indicating these
two hydrogens are neighbours. The presence of two p-
anisyl rings is also evident from the signals between
6.80 and 7.90 ppm and the signals at 3.87 and 3.92
ppm. There are 14 carbons in the aromatic/olefinic
region, seven of them being quaternary. Out of these,
there is a formyl group as evidenced by the signal at
192.6 ppm and the formyl hydrogen has been found to
be vicinal to another olefinic hydrogen. The other two
coupled doublets can be assigned to the C-4 and C-5
hydrogens of the pyrazolyl ring and hence it is clear
that the compound 3 is 3-aryl-3-(3-aryl-1H-1-pyrazolyl)-
2-propenal. There can be two geometrical forms for this
compound and an attempt has been made to establish
the geometry through NOESY spectrum. It is expected
that if the molecule assumes Z geometry, the formyl
hydrogen can give a contour with the hydrogen of the
pyrazolyl ring and if the geometry is E, the olefinic
hydrogen at 7.00 ppm can give a contour with the later
hydrogens. But unfortunately the spatial relation is not
revealed in the NOESY spectrum, which shows only the
dipolar coupling relationship. From the single crystal X-
ray analysis of (3b) [17] (Fig. 1), it is found that 3 is
having a geometry in which the olefinic hydrogen and
the pyrazolyl ring are cis to each other. Thus compound
3 is (E)-3-aryl-3-[3-aryl-1H-1-pyrazolyl]-2-propenal.
Compound 4 has been obtained as the major product
in some cases (4b, 4f, 4g, 4h, 4j, and 4k). The initial
inspection of the 1H- and 13C-NMR spectra of 4c
reveals the presence of two formyl groups. One of the
formyl hydrogen appears as a singlet at 9.96 ppm, while
the other appears as a doublet at 9.49 ppm. The latter
signal has a coupling partner, which appears as a mul-
tiplet along with some other hydrogens in the region
around 7.01 ppm, as evidenced by the H,H-COSY spec-
trum. There is a sharp singlet appearing at 7.93 ppm
accounting for one hydrogen. The presence two aryl
rings are also evident from the spectral pattern. These
results clearly suggest that there is an additional formyl
due to two olefinic hydrogens, the one at 5.87 ppm may
be due to the hydrogen cis to the pyrazolyl ring, as the
pyrazole ring has been shown to exhibit more aniso-
tropic deshielding than simple phenyl group. (Table 1)
It is to be noted that compound 2 has been obtained
as the sole product when the reaction was carried under
conventional condition in 1:2 ratio of substrate and rea-
gent in quantitative yields (40 to 95%) as the only prod-
uct [10]. However in the present investigation, this com-
pound is not obtained as the major product, but as a
minor one with very low yield in some cases. Probably,
the excess formylating agent and the additional energy
available in the form of microwaves would have left 2
as the minor product. Out of the 11 compounds
obtained, 2a, 2b, and 2c are found to be reported in lit-
erature [10].
Compound 3, isolated as the major compound in
some cases (3a, 3c, 3d, 3e, and 3i), exhibits a doublet
around 9.44 ppm and another doublet around 7.00 ppm
(J ¼ 8.3 Hz). For 3c, these two signals are having con-
necting contours in the H,H-COSY spectrum. Two dou-
Table 1
Pyrazole derivatives from substituted acetophenone azines.
Yield %
(MWI)
Yield %
(thermal)
Entry
Ar
2
3
4
2
3
4
a
b
c
D
e
f
g
h
i
Phenyl
25
7
36
34
40
46
33
35
28
34
43
22
–
35
57
38
40
30
40
56
38
30
46
58
15
10
7
40
33
42
44
40
33
25
31
42
24
–
32
45
36
38
35
38
53
35
29
44
55
p-Methylphenyl
p-Methoxy phenyl
p-Chlorophenyl
p-Nitrophenyl
p-Bromophenyl
o-Chlorophenyl
m-Methoxyphenyl
1-Naphthyl
5
7
13
11
14
12
17
16
16
34
12
15
13
20
22
25
35
j
k
2-Naphthyl
o-Methoxyphenyl
Figure 1. ORTEP diagram of compound 3b.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2011
Ring and Side Chain Formylated Pyrazoles from Acetophenone Azines
and Vilsmeier’s Reagent
673
ppm, indicating the latter carbon to C-4 of the pyrazolyl
ring. The formyl hydrogen at 9.49 ppm has a HMBC
contour with the methylenic carbon at 118.6 ppm and
hence this carbon is a to the formyl group. The singlet
at 7.93 ppm has a HMBC contour with the quaternary
carbon at 155.5 ppm and hence this carbon is the C-3
carbon of the pyrazolyl ring. This hydrogen has also a
HMBC contour with the C-4 carbon, already assigned.
It has a C,H-COSY contour with the carbon at 135.9
ppm and hence this carbon is C-5 carbon. The chemical
shift value of the terminal olefinic hydrogen is very
close to that of the compound 3 and hence it can be
assumed to have a similar geometry, the one in which
the olefinic hydrogen and the pyrazolyl ring are cis to
each other. The single crystal X-ray structure of 4b [18]
(Fig. 2) also confirms this assignment.
Figure 2. ORTEP diagram of compound 4b.
group in this compound compared to compound 3. The
absence of pair of doublets due to the pyrazolyl ring
hydrogens and the appearance of only one singlet for
the pyrazolyl hydrogen indicates that the formylation
has occurred in the pyrazolyl ring. Of the two free posi-
tions, by logic, the formyl group can be placed in 4th
position. The 13C-NMR spectrum also supports the
assigned structure. The singlet formyl hydrogen at 9.96
ppm has HMBC contours with the carbon at 135.9 ppm
and this unambiguously indicates that this carbon to be
C-5 of the pyrazolyl ring. This hydrogen has another
HMBC contour with the quartenary carbon at 122.9
The interesting aspect of this reaction of the acetophe-
none azine with excess Vilsmeier’s reagent is the fact
that the simple formylated compound 2, which was orig-
inally obtained as the exclusive product, has now
obtained as a minor one. Two more products 3 and 4
are obtained due to formylation at a different centre and
further formylation, respectively. The mechanism of the
reaction and the reason for the selective formation of 3
and 4 over 2 can be explained as follows:
It has already been established that during the reac-
tion of acetophenone azine with two moles of Vilsme-
ier’s reagent, the reaction takes place by the initial for-
mylation at carbon end followed by formylation at the
nitrogen end to yield the product 2 and not by double
formylation at the methyl end of the acetophenone [10].
Scheme 2
Scheme 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

674
R. Manikannan and S. Muthusubramanian
Vol 48
product. Crude compounds 1a-k were recrystallised from
dichloromethane. All the synthesized substituted acetopheo-
none azines, except 1k, have been reported.
However, under microwave condition and in presence of
excess reagent, it is found that the reaction takes place
not only at the nitrogen and methyl end leading to ulti-
mate cyclisation, but also to a product in which both the
methyl ends of the acetophenone entities have been for-
mylated with subsequent cyclisation leading to 3. Prob-
ably both 2 and 3 would have formed in equal amounts
in the reaction, but due to the presence of excess rea-
gent, 2 would have got further formylated to yield 4,
while 3 has no change of getting further formylated.
The whole sequence of the reaction leading to products
2, 3, and 4 are depicted in the Schemes 2 and 3.
It is interesting to note that with 1e and 1f, apart
from the indicated products 2, 3, and 4, a few minor
products are also obtained. With 1e, three products, 5e,
6e, and 7e are obtained in minor quantities. With 1f, a
small amount of 5f is obtained. These compounds are
identified as the products that can be obtained from the
hydrazone of the respective acetophenones or the aceto-
phenone themselves. The identified minor products from
1e are (E)-3-chloro-3-(4-nitrophenyl)-2-propenal (5e), 3-
(4-nitrophenyl)-1H-pyrazole (6e) and 3-(4-nitrophenyl)-
1H—pyrazole-4-carbaldehyde (7e) and that from 1f is
(E)-3-(4-bromophenyl)-3-chloro-2-propenal (5f). These
compounds would have formed by the initial hydrolysis
of the azine to hydrazone and then to acetophenones by
the moisture in the reaction medium.
1-(2-Methoxyphenyl)-1-ethanone N-[(E)-1-(2-methoxyphe-
nyl)ethylidene]hydrazone (1k). This compound was obtained
as white solid (Dichloromethane), yield 95%; mp 75–76ꢀC;
1
time 2 h; H-NMR (CDCl3, 300 MHz): d 2.23 (s, 6H), 3.89 (s,
6H), 6.93 (d, J ¼ 8.4 Hz, 2H), 7.00 (td, J ¼ 7.5, 0.9 Hz, 2H),
7.35 (td, J ¼ 8.4, 1.8 Hz, 2H), 7.53 (dd, J ¼ 7.5, 1.8 Hz, 2H);
13C-NMR (CDCl3, 75 MHz): d 18.7, 55.4, 111.0, 120.6, 129.4,
129.5, 130.0, 157.4, 158.6. Anal. Calcd. for C18H20N2O2: C,
72.95; H, 6.80; N, 9.45%. Found: C, 73.07; H, 6.91; N,
9.56%.
General procedure for the preparation of pyrazole
derivatives 3-(aryl)-1-[1-(aryl)vinyl]-1H-4-pyrazole car-
baldehyde (2a-k), (E)-3-aryl-3-(3-aryl-1H-1-pyrazolyl)-2-
propenal (3a-j), and 3-(aryl)-1-[(E)-1-(aryl)-3-oxo-1-pro-
penyl]-1H-4-pyrazolecarbaldehyde (4a-k).
Microwave
irradiation method. To a mixture of 1-aryl-1-ethanone N-[(E)-
1-arylethylidene]hydrazones (1) (0.003 mol) and 3 mL of di-
methyl formamide kept in ice bath at 0ꢀC, phosphorous oxy-
cholride (0.024 mole) was added dropwise for 5 to 10 minutes.
The reaction mixture was then irradiated under microwaves for
30 to 60 seconds. The progress of the reaction was monitored
by TLC. After completion of the reaction, the reaction mixture
was poured into crushed ice and extracted with dichlorome-
thane. The organic layer was dried over anhydrous sodium sul-
fate. The different compounds present in the mixture were sep-
arated by column chromatography using petroleum ether and
ethyl acetate mixture as eluent.
Conventional method. To a mixture of 1-aryl-1-ethanone N-
[(E)-1-arylethylidene]hydrazones 1 (0.003 mole) and 3 mL of
dimethyl formamide kept in ice bath at 0ꢀC, phosphorous oxy-
cholride (0.024 mole) was added dropwise for 5 to 10 minutes.
The reaction mixture was then stirred with reflux for 4 to 5 h
at 80ꢀC. The progress of the reaction was monitored by TLC.
After completion of the reaction, the reaction mixture was
poured into crushed ice and extracted with dichloromethane.
The organic layer was dried over anhydrous sodium sulfate.
The different compounds present in the mixture were separated
by column chromatography using petroleum ether and ethyl
acetate mixture as eluent.
3-Phenyl-1-(1-phenylvinyl)-1H-4-pyrazolecarbaldehyde
(2a). This compound was obtained as white solid (Dichloro-
methane), mp 63–64 (62)ꢀC [19]; 1H-NMR (CDCl3, 300
MHz): d 5.35 (s, 1H), 5.91(s, 1H), 7.41–7.45 (m, 8H), 7.79–
7.82 (m, 2H), 8.06 (s, 1H), 9.98 (s, 1H); 13C-NMR (CDCl3, 75
MHz): d 107.5, 121.6, 128.1, 128.7, 128.8, 129.0, 129.3,
129.8, 131.2, 134.0, 134.4, 144.8, 154.6, 185.1. Anal. Calcd.
for C18H14N2O: C, 78.81; H, 5.14; N, 10.21%. Found: C,
78.85; H, 5.19; N, 10.27%.
This article summarises the effect excess reagent dur-
ing the Vilsmeier reaction of acetophenone azines under
thermal and microwave conditions to get differently for-
mylated and diformylated products apart form the sim-
ple formylated product. The mechanisms for the forma-
tion of the different products have been described.
EXPERIMENTAL
All chemicals used in this investigation were of reagent
grade quality and used without further purification. All melting
points were recorded in open capillaries and are uncorrected.
1
The H- and 13C-NMR spectra were recorded on a Bruker 300
MHz spectrometer at 300 and 75 MHz, respectively in CDCl3/
DMSO-d6 using TMS as internal standard. The chemical shifts
are presented in d-scale. Microanalyses were carried out on a
Perkin-Elmer instrument. Microwave assisted reactions were
carried out in a Biotage Microwave Synthesizer. All chromato-
graphic separations were performed on 60–120 mesh silica gel
using petroleum ether-ethyl acetate as eluent, unless mentioned
otherwise. Single crystal XRD data were collected on a
APEX2 (BRUKER, 2004).
3-(4-Methylphenyl)-1-[1-(4-methylphenyl) vinyl]-1H-4-py-
razolecarbaldehyde (2b). This compound was obtained as
1
white solid (Dichloromethane), mp 115–116 (116)ꢀC [19]; H-
General procedure for the preparation of 1-aryl-1-etha-
none N-[(E)-1-arylethylidene]hydrazones (1a-k). A mixture
of substituted acetophenone (0.005 mol) and hydrazine sulfate
(0.002 mol) in presence of sodium acetate (0.008 mole) in
ethanol medium was refluxed for 1 to 2 h. The reaction was
monitored by TLC. After completion of the reaction, the reac-
tion mixture was poured into crushed ice then filtered the
NMR (CDCl3, 300 MHz): d 2.42 (s, 3H), 2.43 (s, 3H), 5.31(s,
1H), 5.87 (s, 1H), 7.24–7.34 (m, 6H), 7.71 (d, J ¼ 7.8 Hz,
2H), 8.05 (s, 1H), 9.98 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d
21.3, 21.4, 106.7, 121.5, 128.1, 128.3, 128.8, 129.4, 129.5,
131.6, 134.0, 139.3, 139.9, 144.8, 154.5, 185.2. Anal. Calcd.
for C20H18N2O: C, 79.44; H, 6.00; N, 9.26%. Found: C, 79.47;
H, 6.06; N, 9.29%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2011
Ring and Side Chain Formylated Pyrazoles from Acetophenone Azines
and Vilsmeier’s Reagent
675
7.51–7.96 (m, 13H), 8.15 (s, 1H), 8.37(s, 1H), 10.09 (s, 1H);
13C-NMR (CDCl3, 75 MHz): d 108.2, 121.9, 125.1, 126.2,
126.5, 126.8, 126.9, 127.2, 127.7, 127.8, 128.0, 128.4, 128.4,
128.5, 128.6, 128.7*, 131.8, 133.0, 133.2, 133.6, 133.7, 134.6,
145.0, 154.4, 185.0 (*One carbon merged with other).
3-(2-Methoxyphenyl)-1-[1-(2-methoxyphenyl)vinyl]-1H-4-
pyrazolecarbaldehyde (2k). This compound was obtained as
white solid (Dichloromethane), mp 88–89ꢀC; 1H-NMR
(CDCl3, 300 MHz): d 5.12 (s, 3H), 6.14 (s, 3H), 6.97–7.14 (m,
5H), 7.36 (d, J ¼ 7.5 Hz, 1H), 7.43–7.48 (m, 3H), 7.63 (d, J
¼ 7.5 Hz, 1H), 7.78 (s, 1H), 9.70 (s, 1H); 13C-NMR (CDCl3,
75 MHz): d 55.4, 55.7, 106.6, 111.0, 111.1, 120.6, 120.9,
121.0, 122.2, 123.4, 130.8, 130.9, 131.4*, 131.7, 141.8, 151.8,
156.9, 157.3, 186.8 (*One carbon merged with other). Anal.
Calcd. for C20H18N2O3: C, 71.84; H, 5.43; N, 8.38%. Found:
C, 71.89; H, 5.48; N, 8.41%.
(E)-3-Phenyl-3-(3-phenyl-1H-1-pyrazolyl)-2-propenal (3a). This
compound was obtained as white solid (Dichloromethane), mp
118–119ꢀC; 1H-NMR (CDCl3, 300 MHz): d 6.74 (d, J ¼ 2.7
Hz, 1H), 7.09 (d, J ¼ 8.3 Hz, 1H), 7.27 (d, J ¼ 2.7 Hz, 1H),
7.34–7.62 (m, 8H), 7.91 (d, J ¼ 8.1 Hz, 2H), 9.42 (d, J ¼ 8.3
Hz, 1H); 13C-NMR (CDCl3, 75 MHz): d 106.8, 116.4, 126.2,
128.8, 128.9, 129.1, 130.6, 130.8, 131.1, 131.8, 132.1, 155.4,
155.8, 192.4. Anal Calcd for C18H14N2O: C, 78.81; H, 5.14;
N, 10.21%. Found: C, 78.88; H, 5.17; N, 10.27%.
(E)-3-(4-Methylphenyl)-3-[3-(4-methylphenyl)-1H-1-pyra-
zolyl]-2-propenal (3b). This compound was obtained as white
solid (Dichloromethane), mp 174–175ꢀC; 1H-NMR (CDCl3,
300 MHz): d 2.41(s, 3H), 2.48 (s, 3H), 6.71 (d, J ¼ 2.4 Hz,
1H), 7.05 (d, J ¼ 8.4 Hz, 1H), 7.25–7.31 (m, 3H), 7.42 (d, J
¼ 7.8 Hz, 2H), 7.80 (d, J ¼ 8.1 Hz, 2H), 9.43 (d, J ¼ 8.4 Hz,
1H); 13C-NMR (CDCl3, 75 MHz): d 21.4, 21.5, 106.5, 116.2,
126.1, 127.6, 129.0, 129.4, 129.5, 130.8, 132.1, 139.0, 141.5,
155.4, 156.1, 192.6. Anal. Calcd. for C20H18N2O: C, 79.44; H,
6.00; N, 9.26%. Found: C, 79.49; H, 6.09; N, 9.31%.
(E)-3-(4-Methoxyphenyl)-3-[3-(4-methoxyphenyl)-1H-1-py-
razolyl]-2-propenal (3c). This compound was obtained as
white solid (Dichloromethane), mp 127–128ꢀC; 1H-NMR
(CDCl3, 300 MHz): d 3.87 (s, 3H), 3.92 (s, 3H), 6.69 (d, J ¼
2.7 Hz, 1H), 6.97 (d, J ¼ 8.7 Hz, 2H), 7.00 (d, J ¼ 8.3 Hz,
1H), 7.05 (d, J ¼ 8.7 Hz, 2H), 7.32 (d, J ¼ 2.7 Hz, 1H), 7.45
(d, J ¼ 8.9 Hz, 2H), 7.84 (d, J ¼ 8.9 Hz, 2H), 9.44 (d, J ¼
8.3 Hz, 1H); 13C-NMR (CDCl3, 75 MHz): d 55.3, 55.5, 106.3,
114.2, 114.3, 116.1, 122.7, 124.6, 127.5, 132.1, 132.5, 155.2,
155.9, 160.4, 161.8, 192.6. Anal. Calcd. for C20H18N2O3: C,
71.84; H, 5.43; N, 8.38%. Found: C, 71.88; H, 5.47; N,
8.42%.
(E)-3-(4-Chlorophenyl)-3-[3-(4-chlorophenyl)-1H-1-pyraz-
olyl]-2-propenal (3d). This compound was obtained as white
solid (Dichloromethane), mp 144–145ꢀC; 1H-NMR (CDCl3,
300 MHz): d 6.74 (d, J ¼ 2.7 Hz, 1H), 7.04 (d, J ¼ 8.1 Hz,
1H), 7.31 (d, J ¼ 2.7 Hz, 1H), 7.42 (d, J ¼ 8.4 Hz, 2H), 7.48
(d, J ¼ 8.4 Hz, 2H), 7.57 (d, J ¼ 8.4 Hz, 2H), 7.83 (d, J ¼
8.4 Hz, 2H), 9.43 (d, J ¼ 8.1 Hz, 1H); 13C-NMR (CDCl3, 75
MHz): d 106.9, 116.8, 127.4, 128.8, 129.0, 129.4, 130.2,
132.0, 132.1, 135.0, 137.6, 154.3, 154.4, 191.7. Anal. Calcd.
for C18H12Cl2N2O: C, 62.99; H, 3.52; N, 8.16%. Found: C,
63.02; H, 3.56; N, 8.19%.
3-(4-Methoxyphenyl)-1-[1-(4-methoxyphenyl) vinyl]-1H-4-
pyrazolecarbaldehyde (2c). This compound was obtained as
1
white solid (Dichloromethane), mp 105–106 (105)ꢀC [19]; H-
NMR (CDCl3, 300 MHz): d 3.86 (s, 3H), 3.89 (s, 3H), 5.25 (s,
1H), 5.78 (s,1H), 6.94 (d, J ¼ 8.9, Hz, 2H), 7.00 (d, J ¼ 8.9
Hz, 2H), 7.34 (d, J ¼ 8.7 Hz, 2H), 7.77 (d, J ¼ 8.7 Hz, 2H),
8.03 (s, 1H); 9.95 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d
55.3, 55.4, 106.2, 114.1, 114.2, 121.3, 123.7, 126.9, 129.5,
130.3, 134.4, 144.5, 154.2, 160.5, 160.7, 185.1. Anal. Calcd.
for C20H18N2O3: C, 71.84; H, 5.43; N, 8.38%. Found: C,
71.89; H, 5.47; N, 8.42%.
3-(4-Chlorophenyl)-1-[1-(4-chlorophenyl) vinyl]-1H-4-py-
razolecarbaldehyde (2d). This compound was obtained as
1
viscous oil; H-NMR (CDCl3, 300 MHz): d 5.37 (s, 1H), 5.85
(s, 1H), 7.35 (d, J ¼ 8.7 Hz, 2H), 7.41–7.46 (m, 4H), 7.79 (d,
J ¼ 8.4 Hz, 2H), 8.01 (s, 1H), 9.95 (s, 1H); 13C-NMR
(CDCl3, 75 MHz): d 108.2, 121.7, 128.9, 129.1, 129.3, 129.6,
130.2, 132.8, 135.1, 135.5, 136.0, 143.9, 153.0, 184.3.
3-(4-Nitrophenyl)-1-[1-(4-nitrophenyl)vinyl]-1H-4-pyra-
zolecarbaldehyde (2e). This compound was obtained as vis-
1
cous oil; H-NMR (CDCl3, 300 MHz): d 5.62 (d, J ¼ 1.7 Hz,
1H), 5.98 (d, J ¼ 1.7 Hz, 1H), 7.61 (d, J ¼ 8.9 Hz, 2H), 8.09
(d, J ¼ 8.9 Hz, 2H), 8.20 (s, 1H), 8.30–8.32 (m, 4H), 10.02 (s,
1H); 13C-NMR (CDCl3, 75 MHz): d 111.3, 122.5, 123.8,
124.2, 126.9, 128.9, 129.8, 132.0, 136.5, 140.2, 143.3, 148.2,
153.2, 183.4.
3-(4-Bromophenyl)-1-[1-(4-bromophenyl) vinyl]-1H-4-py-
razolecarbaldehyde (2f). This compound was obtained as vis-
1
cous oil; H-NMR (CDCl3, 300 MHz): d 5.38 (s, 1H), 5.86 (s,
1H), 7.25–7.76 (m, 8H), 8.10 (s, 1H), 10.0 (s, 1H); 13C-NMR
(CDCl3, 75 MHz): d 108.2, 121.7, 123.8, 124.5, 129.6, 130.1,
130.4, 131.9, 132.1, 133.3, 135.1, 143.9, 153.1, 184.2.
3-(2-Chlorophenyl)-1-[1-(2-chlorophenyl)vinyl]-1H-4-py-
razolecarbaldehyde (2g). This compound was obtained as
1
viscous oil; H-NMR (CDCl3, 300 MHz): d 5.21 (s, 1H), 6.18
(s, 1H), 7.16–7.51 (m, 8H), 7.82 (s, 1H), 9.71 (s, 1H); 13C-
NMR (CDCl3, 75 MHz): d 108.2, 122.5, 126.9, 127.0, 127.3,
129.9, 130.1, 130.2, 130.4, 130.6, 131.2, 132.1, 133.3, 133.7,
133.9, 141.9, 152.5, 185.1.
3-(3-Methoxyphenyl)-1-[1-(3-methoxyphenyl)vinyl]-1H-4-
pyrazolecarbaldehyde (2h). This compound was obtained as
white solid (Dichloromethane), mp 98–99ꢀC; 1H-NMR
(CDCl3, 300 MHz): d 3.81 (s, 3H), 3.86 (s, 3H), 5.33 (s, 1H),
5.90 (s, 1H), 6.95-7.00 (m, 4H), 7.26–7.37 (m, 4H), 8.05 (s,
1H), 9.96 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d 55.27*,
107.5, 113.9, 114.1, 115.1, 115.2, 120.4, 121.4, 121.6, 129.7,
129.9, 132.4, 134.1, 135.7, 144.5, 154.3, 159.7, 158.8, 185.0
(* One carbon merged with other). Anal. Calcd. for
C20H18N2O3: C, 71.84; H, 5.43; N, 8.38%. Found: C, 71.88;
H, 5.50; N, 8.43%.
3-(1-Naphthyl)-1-[1-(1-naphthyl)vinyl]-1H-4-pyrazolecar-
baldehyde (2i). This compound was obtained as viscous oil;
1H-NMR (CDCl3, 300 MHz): d (s, 1H), 6.45 (s, 1H), 7.52–
8.08 (m, 15H), 9.53 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d
108.1, 123.1, 124.6, 125.1, 125.4, 125.5, 126.3, 126.6, 126.9*,
127.3, 128.2, 128.4, 128.7, 128.8, 129.0, 129.8, 130.5, 131.5,
131.7, 132.0, 133.7, 133.8, 142.6, 154.4, 185.6 (*One carbon
merged with other).
3-(2-Naphthyl)-1-[1-(2-naphthyl)vinyl]-1H-4-pyrazolecar-
baldehyde (2j). This compound was obtained as viscous oil;
1H-NMR (CDCl3, 300 MHz): d 5.52 (s, 1H), 6.03 (s, 1H),
(E)-3-(4-Nitrophenyl)-3-[3-(4-nitrophenyl)-1H-1-pyrazo-
lyl]-2-propenal (3e). This compound was obtained as white
solid (Dichloromethane), mp 170–172ꢀC; 1H-NMR (CDCl3,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

676
R. Manikannan and S. Muthusubramanian
Vol 48
300 MHz): d 6.90 (d, J ¼ 2.7 Hz, 1H), 7.09 (d, J ¼ 8.1 Hz,
1H), 7.41 (d, J ¼ 2.7 Hz, 1H), 7.78 (d, J ¼ 8.4 Hz, 2H), 8.03
(d, J ¼ 8.7 Hz, 2H), 8.30 (d, J ¼ 8.4 Hz, 2H), 8.47 (d, J ¼
8.4 Hz, 2H), 9.44 (d, J ¼ 8.1 Hz, 1H); 13C-NMR (CDCl3, 75
MHz): d 108.0, 117.9, 124.1, 124.2*, 126.8, 132.0, 136.4,
137.5, 148.0, 149.9, 152.7, 153.4, 190.5 (*One carbon merged
with other). Anal. Calcd. for C18H12N4O5: C, 59.34; H, 3.32;
N, 15.38%. Found: C, 59.41; H, 3.39; N, 15.38%.
(E)-3-(4-Bromophenyl)-3-[3-(4-bromophenyl)-1H-1-py-
razolyl]-2-propenal (3f). This compound was obtained as
white solid (Dichloromethane), mp 146–147ꢀC; 1H-NMR
(CDCl3, 300 MHz): d 6.73 (d, J ¼ 2.7 Hz, 1H), 7.02 (d, J ¼
8.3 Hz, 1H), 7.29 (d, J ¼ 2.7 Hz, 1H), 7.39 (d, J ¼ 8.4 Hz,
2H), 7.57 (d, J ¼ 8.7 Hz, 2H), 7.71(d, J ¼ 8.4 Hz, 2H), 7.75
(d, J ¼ 8.4 Hz, 2H), 9.41 (d, J ¼ 8.1 Hz, 1H); 13C-NMR
(CDCl3, 75 MHz): d 106.9, 116.9, 123.3, 125.9, 127.7, 129.3,
130.6, 132.0*, 132.2, 132.3, 154.4, 154.5, 191.6 (*One carbon
merged with other). Anal. Calcd. for C18H12Br2N2O: C, 50.03;
H, 2.80; N, 6.48%. Found: C, 50.08; H, 2.86; N, 6.53%.
7.89 (s, 1H), 9.47 (d, J ¼ 8 Hz, 1H), 9.98 (s, 1H); 13C-NMR
(CDCl3, 75 MHz): d 118.9, 123.3, 128.9*, 128.9, 129.4, 130.0,
130.4, 130.7, 131.6, 135.4, 154.5, 156.0, 184.6, 191.8 (*One
carbon merge with other). Anal. Calcd. for C19H14N2O2: C,
75.48; H, 4.67; N, 9.27%. Found: C, 75.52; H, 4.70; N,
9.31%.
3-(4-Methylphenyl)-1-[(E)-1-(4-methylphenyl)-3-oxo-1-pro-
penyl]-1H-4-pyrazolecarbaldehyde (4b). This compound was
obtained as white solid (Dichloromethane), mp 141–142ꢀC;
1H-NMR (CDCl3, 300 MHz): d 2.45 (s, 3H), 2.51 (s, 3H),
7.12 (d, J ¼ 8.1 Hz, 1H), 7.34 (d, J ¼ 7.8 Hz, 2H), 7.38–7.41
(m, 4H), 7.73 (d, J ¼ 8.1 Hz, 2H), 7.91 (s, 1H), 9.49 (d, J ¼
8.1 Hz, 1H), 9.98 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d
21.4, 21.5, 118.7, 123.2, 126.5, 127.6, 128.8, 129.6, 130.0,
130.7, 135.4, 140.1, 142.2, 154.8, 156.0, 184.8, 192.1. Anal.
Calcd. for C21H18N2O2: C, 76.34; H, 5.49; N, 8.48%. Found:
C, 76.39; H, 5.52; N, 8.54%.
3-(4-Methoxyphenyl)-1-[(E)-1-(4-methoxyphenyl)-3-oxo-1-
propenyl]-1H-4-pyrazolecarbaldehyde (4c). This compound
was obtained as viscous oil; 1H-NMR (CDCl3, 300 MHz): d
3.88 (s, 3H), 3.93 (s, 3H), 7.02–7.10 (m, 5H), 7.45 (d, J ¼ 8.7
Hz, 2H), 7.81 (d, J ¼ 8.7 Hz, 2H), 7.93 (s, 1H), 9.49 (d, J ¼
8.1 Hz, 1H), 9.96 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d
55.4, 55.6, 114.3, 114.7, 118.6, 121.4, 122.9, 123.1, 130.3,
132.4, 135.9, 154.6, 155.5, 161.0, 162.2, 184.6, 192.1.
3-(4-Chlorophenyl)-1-[(E)-1-(4-chlorophenyl)-3-oxo-1-pro-
penyl]-1H-4-pyrazolecarbaldehyde (4d). This compound was
obtained as white solid (Dichloromethane), mp 150–151ꢀC;
1H-NMR (CDCl3, 300 MHz): d 7.11 (d, J ¼ 7.8 Hz, 1H),
7.48–7.51 (m, 4H), 7.61 (d, J ¼ 8.4 Hz, 2H), 7.83 (d, J ¼ 8.4
Hz, 2H), 7.89 (s, 1H), 9.48 (d, J ¼ 7.8 Hz, 1H), 9.95 (s, 1H);
13C-NMR (CDCl3, 75 MHz): d 119.2, 123.5, 127.6, 128.7,
129.1, 129.8, 130.2, 132.0, 136.1, 136.2, 138.3, 153.0, 154.5,
183.8, 191.1. Anal. Calcd. for C19H12Cl2N2O2: C, 61.47; H,
3.26; N, 7.55%. Found: C, 61.50; H, 3.30; N, 7.59%.
(E)-3-(2-Chlorophenyl)-3-[3-(2-chlorophenyl)-1H-1-pyraz-
olyl]-2-propenal (3g). This compound was obtained as viscous
1
oil; H-NMR (CDCl3, 300 MHz): d 6.98 (d, J ¼ 2.7 Hz, 1H),
7.14 (d, J ¼ 8.4 Hz, 1H), 7.21 (d, J ¼ 2.7 Hz, 1H), 7.31–7.62
(m, 7H), 7.92 (dd, J ¼ 6.9 Hz, 1H), 9.32 (d, J ¼ 8.4 Hz, 1H);
13C-NMR (CDCl3, 75 MHz): d 110.8, 116.5, 127.0, 127.2,
129.5, 130.0, 130.1, 130.2*, 130.7, 130.8, 132.2, 132.5, 132.6,
134.5, 152.6, 153.5, 191.4 (*One carbon merged with other).
(E)-3-(3-Methoxyphenyl)-3-[3-(3-methoxyphenyl)-1H-1-py-
razolyl]-2-propenal (3h). This compound was obtained as vis-
1
cous oil; H-NMR (CDCl3, 300 MHz): d 3.85 (s, 3H), 3.89 (s,
3H), 6.72 (d, J ¼ 2.7 Hz, 1H), 6.95 (d, J ¼ 8.1 Hz, 1H),
7.04–7.49 (m, 9H), 9.44 (d, J ¼ 8.1 Hz, 1H); 13C-NMR
(CDCl3, 75 MHz): d 55.3, 55.5, 106.9, 110.9, 115.2, 116.1,
116.2, 116.6, 118.7, 123.1, 129.8, 130.0, 131.6, 132.2, 133.1,
155.2, 155.5, 159.7, 159.9, 192.5.
(E)-3-(1-Naphthyl)-3-[3-(1-naphthyl)-1H-1-pyrazolyl]-2-
propenal (3i). This compound was obtained as white solid
(Dichloromethane), mp 117–118ꢀC; 1H-NMR (CDCl3, 300
MHz): d 6.67 (d, J ¼ 2.7 Hz, 1H), 7.11 (d, J ¼ 2.7 Hz, 1H),
7.42 (d, J ¼ 8.4 Hz, 1H), 7.53–8.13 (m, 13H), 8.79 (d, J ¼
9.00 Hz, 1H), 9.32 (d, J ¼ 8.4 Hz, 1H); 13C-NMR (CDCl3, 75
MHz): d 110.4, 117.1, 124.8, 125.0, 125.2, 126.0, 126.1,
126.9, 127.0, 127.6, 127.7, 128.0, 128.4, 128.6, 129.5, 129.6,
129.9, 130.9, 131.1, 131.4, 132.0, 133.5, 134.0, 154.6, 155.7,
192.3. Anal. Calcd. for C26H18N2O: C, 83.40; H, 4.85; N,
7.48%. Found: C, 83.45; H, 4.89; N, 7.51%.
(E)-3-(2-Naphthyl)-3-[3-(2-naphthyl)-1H-1-pyrazolyl]-2-
propenal (3j). This compound was obtained as white solid
(Dichloromethane), mp 92–93ꢀC; 1H-NMR (CDCl3, 300
MHz): d 6.90 (d, J ¼ 2.7 Hz, 1H); 7.23 (d, J ¼ 8.1 Hz, 1H),
7.36 (d, J ¼ 2.7 Hz, 1H), 7.54–8.15 (m, 14H), 9.50 (d, J ¼
8.1 Hz, 1H); 13C-NMR (CDCl3, 75 MHz): d 107.0, 116.9,
123.9, 125.5, 126.4, 126.5, 126.7, 127.5, 127.7, 127.8, 127.9,
128.1, 128.4, 128.5, 128.6, 128.9, 129.2, 131.7, 132.4, 132.5,
133.4, 133.7, 134.1, 155.4, 155.5, 192.5. Anal. Calcd. for
C26H18N2O: C, 83.40; H, 4.85; N, 7.48%. Found: C, 83.47; H,
4.88; N, 7.53%.
3-(4-Nitrophenyl)-1-[(E)-1-(4-nitrophenyl)-3-oxo-1- prope-
nyl]-1H-4-pyrazolecarbaldehyde (4e). H-NMR (CDCl3, 300
MHz): d 7.19 (d, J ¼ 7.8 Hz, 1H), 7.79 (d, J ¼ 8.6 Hz, 2H),
7.93 (s, 1H), 8.12 (d, J ¼ 8.6 Hz, 2H), 8.36 (d, J ¼ 8.6 Hz,
2H), 8.51 (d, J ¼ 8.6 Hz, 2H), 9.48 (d, J ¼ 7.8 Hz, 1H);
10.05 (s, 1H).
1
3-(4-Bromophenyl)-1-[(E)-1-(4-bromophenyl)-3-oxo-1-pro-
penyl]-1H-4-pyrazolecarbaldehyde (4f). This compound was
obtained as white solid (Dichloromethane), mp 198–199ꢀC;
1H-NMR (CDCl3 300 MHz): d 7.23 (d, J ¼ 7.8 Hz, 1H), 7.41
(d, J ¼ 7.8 Hz, 2H), 7.65 (d, J ¼ 8.4 Hz, 2H), 7.51–7.78 (m,
4H), 7.89 (s, 1H), 9.48 (d, J ¼ 7.8 Hz, 1H), 9.95 (s, 1H); 13C-
NMR (CDCl3, 75 MHz): d 119.2, 123.5, 124.6, 126.6, 128.1,
129.2, 130.4, 132.1, 132.2, 132.8, 136.2, 153.1, 154.6, 183.8,
191.1. Anal. Calcd. for C19H12Br2N2O2: C, 49.60; H, 2.63; N,
6.09%. Found: C, 49.68; H, 2.67; N, 6.17%.
3-(2-Chlorophenyl)-1-[(E)-1-(2-chlorophenyl)-3-oxo-1-pro-
penyl]-1H-4-pyrazolecarbaldehyde (4g). This compound was
obtained as viscous oil; 1H-NMR (CDCl3, 300 MHz): d 7.19 (d,
J ¼ 8.1 Hz, 1H), 7.43–7.65 (m, 8H), 7.78 (s, 1H), 9.38 (d, J ¼
8.1 Hz, 1H), 9.72 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d 119.2,
124.1, 127.1, 127.6, 128.5, 129.6, 130.0, 130.8, 131.1, 131.9,
132.5, 132.7, 132.8, 133.4, 134.5, 151.4, 154.1, 184.7, 190.8.
3-(3-Methoxyphenyl)-1-[(E)-1-(3-methoxyphenyl)-3-oxo-1-
propenyl]-1H-4-pyrazolecarbaldehyde (4h). This compound
was obtained as white solid (Dichloromethane), mp 157–158ꢀC;
1-[(E)-3-Oxo-1-phenyl-1-propenyl]-3-phenyl-1H-4-pyrazo-
lecarbaldehyde (4a). This compound was obtained as white
solid (Dichloromethane), mp 152–153ꢀC; 1H-NMR (CDCl3,
300 MHz): d 7.15 (d, J ¼ 8 Hz, 1H), 7.52–7.84 (m, 10H),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2011
Ring and Side Chain Formylated Pyrazoles from Acetophenone Azines
and Vilsmeier’s Reagent
677
1H-NMR (CDCl3, 300 MHz): d 3.87 (s, 3H), 3.89 (s, 3H), 7.02–
7.18 (m, 5H), 7.36–7.52 (m, 4H), 7.90 (s, 1H), 9.48 (d, J ¼ 8.1
Hz, 1H), 9.97 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d 55.4, 55.5,
113.9, 115.9, 116.2, 116.9, 118.7, 121.4, 122.9, 123.3, 129.9,
1305, 130.6, 131.7, 135.4, 154.3, 155.8, 159.9, 160.0, 184.7,
191.9. Anal. Calcd. for C21H18N2O4: C, 69.60; H, 5.01; N,
7.73%. Found: C, 69.68; H, 5.10; N, 7.82%.
(E)-3-(4-Bromophenyl)-3-chloro-2-propenal (5f). This
compound was obtained as viscous liquid [22]; 1H-NMR
(CDCl3, 300 MHz): d 6.66 (d, J ¼ 6.9 Hz, 1H), 7.62 (d, J ¼
8.7 Hz, 2H), 7.82 (d, J ¼ 8.7 Hz, 2H), 10.21 (d, J ¼ 6.9 Hz,
1H); 13C-NMR (CDCl3, 75 MHz): d 124.5, 128.5, 129.8,
131.9, 132.0, 150.9, 191.2.
3-(1-Naphthyl)-1-[(E)-1-(1-naphthyl)-3-oxo-1-propenyl]-1H-
4-pyrazolecarbaldehyde (4i). This compound was obtained as
white solid (Dichloromethane), mp 85–86ꢀC; 1H-NMR
(CDCl3, 300 MHz): d 7.44 (d, J ¼ 8 Hz, 1H), 7.57–8.18 (m,
15H), 9.35 (d, J ¼ 8 Hz, 1H), 9.56 (s, 1H); 13C-NMR (CDCl3,
75 MHz): d 120.0, 124.2, 124.6, 125.1, 125.2*, 126.4, 126.5,
127.2, 127.3, 127.8, 128.4, 128.6, 129.0, 129.1 130.1, 130.4,
131.7, 131.8, 132.0, 133.3, 133.7, 133.8, 153.4, 155.8, 185.2,
191.7 (*one carbon merged with other). Anal. Calcd. for
C27H18N2O2: C, 80.58; H, 4.51; N, 6.96%. Found: C, 80.63;
H, 4.59; N, 6.99%.
Acknowledgments. The authors thank DST, New Delhi for as-
sistance under the IRHPA program for the NMR facility. One of
the authors (R.M.) thanks Madurai Kamaraj University for a
research fellowship.
REFERENCES AND NOTES
[1] Windholz, M., Ed. The Merck Index, 9th ed.; Merck &
Co.: Rahway, New Jersey, 1976; p 291.
3-(2-Naphthyl)-1-[(E)-1-(2-naphthyl)-3-oxo-1-propenyl]-1H-
4-pyrazolecarbaldehyde (4j). This compound was obtained as
white solid (Dichloromethane), mp 155–156ꢀC; 1H-NMR
(CDCl3, 300 MHz): d 7.28 (d, J ¼ 8.1 Hz, 1H), 7.55–8.10 (m,
14 H), 8.39 (s, 1H), 9.55 (d, J ¼ 8.1 Hz, 1H), 10.05 (s, 1H);
13C-NMR (CDCl3, 75 MHz): d 119.3, 123.6, 125.8, 126.2,
126.5, 126.7, 127.2, 127.8*, 128.0, 128.5*, 128.6, 128.7,
128.8, 129.0, 129.5, 131.8, 132.6, 133.1, 133.8, 134.3, 136.0,
154.6, 155.8, 184.5, 191.9 (*one carbon merged with other).
Anal. Calcd. for C27H18N2O2: C, 80.58; H, 4.51; N, 6.96%.
Found: C, 80.67; H, 4.55; N, 7.01%.
3-(2-Methoxyphenyl)-1-[(E)-1-(2-methoxyphenyl)-3-oxo-1-
propenyl]-1H-4-pyrazolecarbaldehyde (4k). This compound
was obtained as white solid (Dichloromethane), mp 108–
109ꢀC; 1H-NMR (CDCl3, 300 MHz): d 3.80 (s, 3H), 3.82 (s,
3H), 7.02–7.17 (m, 5H), 7.37 (dd, J ¼ 7.5, 1.5 Hz, 1H), 7.48
(td, J ¼ 8.7, 1.5 Hz, 1H), 7.59 (td, J ¼ 8.7 Hz, 1H), 7.64 (dd,
J ¼ 7.5, 1.5 Hz, 1H), 7.78 (s, 1H), 9.38 (d, J ¼ 8.4 Hz, 1H),
9.69 (s, 1H); 13C-NMR (CDCl3, 75 MHz): d 55.4, 55.7, 111.1,
111.6, 118.0, 118.4, 119.7, 121.0, 121.2, 123.9, 131.2, 131.4,
132.2, 132.5, 133.1, 152.1, 153.4, 156.8, 157.7, 186.4, 192.1.
Anal. Calcd. for C21H18N2O4: C, 69.60; H, 5.01; N, 7.73%.
Found: C, 69.64; H, 5.06; N, 7.77%.
(E)-3-Chloro-3-(4-nitrophenyl)-2-propenal (5e). This com-
pound was obtained as white solid (Dichloromethane), mp 75–
76ꢀC [20]; 1H-NMR (CDCl3, 300 MHz): d 6.75 (d, J ¼ 6.6
Hz, 1H), 7.92 (d, J ¼ 9 Hz, 2H), 8.33 (d, J ¼ 9.3 Hz, 2H),
10.25 (d, J ¼ 6.9 Hz, 1H); 13C-NMR (CDCl3, 75 MHz): d
121.0, 126.8, 128.2, 141.4, 148.9, 149.4, 190.6.
3-(4-Nitrophenyl)-1H-pyrazole (6e). This compound was
obtained as white solid (Dichloromethane), mp 108–109
(192)ꢀC [21]; 1H-NMR (CDCl3, 300 MHz): d 1.25 (s, 1H),
6.77 (d, J ¼ 1.8 Hz, 1H), 7.69 (d, J ¼ 2.1 Hz, 1H), 7.98 (d, J
¼ 8.7 Hz, 2H), 8.28 (d, J ¼ 8.7 Hz, 2H); 13C-NMR (CDCl3,
75 MHz): d 103.7, 124.1, 126.2, 130.9, 139.2, 147.2, 149.2.
Anal. Calcd. for C9H7N3O2: C, 57.14; H, 3.73; N, 22.21%.
Found: C, 57.25; H, 3.81; N, 22.30%.
[2] Sridhar, R.; Perumal, P. T; Etti, S.; Shanmugam, G.; Pon-
nuswamy, M. N.; Prabavathy, V. R.; Mathivanan, N. Bioorg Med
Chem Lett 2004, 14, 6035.
[3] Wolff, M. E. Burger’s Medicinal Chemistry, 4th ed.;
Wiley: New York, 1980, p 291–296, 301–303.
[4] Garg, H. G.; Singhal, A.; Mathur, J. M. L. J Pharm Sci
1973, 62, 494.
[5] Abadi, A. H.; Eissa, A. A. H.; Hassan, G. S. Chem Pharm
Bul 2003, 51, 838.
[6] Haufel, J.; Breitmaier, E. Angew Chem 1974, 13, 604.
[7] Wustrow, D. J.; Capiris, T.; Rubin, R.; Knobeldorf, J. A.;
Zoski, K. T.; Heffiner, T. G.; Wise, L. D. Bioorg Med Chem Lett
1998, 8, 2067.
[8] Tsutomu, I.; Toshiaki, K.; Hitoshi, S.; Yoshinori, T.; Katsu-
toshi, I. Jpn Kokai Tokkyo Koho JP 01,106,866 [89, 106, 866] (Cl.
C07D231/14), 24 Apr 1989, Appl. 87/261, 738, 19 Oct. 1987; pp 8;
Chem Abstr 1989, 111, 194759h.
[9] Tsutomu, I.; Hideo, Y.; Toshiaki, K.; Hitoshi, S.; Yoshinori,
T.; Katsutoshi, I. Jpn Kokai Tokkyo Koho JP 01,113,371[89, 113,
371] (Cl. C07D231/14), 02 May 1989, Appl. 87/266, 612, 23 Oct.
1987; pp 11; Chem Abstr 1989, 111, 214479x.
[10] Kira, M. A.; Nofal, Z. M.; Gadalla, K. Z. Tetrahedron Lett
1970, 11, 4215.
[11] Nanjundaswamy, H. M.; Pasha, M. A. Synth Commun
2007, 37, 3417.
[12] Nenajdenko, V. G.; Verseev, G. N.; Shastin, A. V.; Balen-
kova, E. S. J Fluorine Chem 2005, 126, 907.
[13] Mira, C.; Shlomo, R. Tetraheadron Lett 2006, 47, 763.
[14] Shastin, A. V.; Korotchenko, V. N.; Varseev, G. N.;
Nenajdenko, V. G.; Balenkova, E. S. Russ J Org Chem 2003, 39, 403.
[15] Miroslaw, G.; Jacek, M. Synth Commun 1999, 29, 4307.
[16] Love, B. E.; Tsai, L. Synth Commun 1992, 22, 3101.
[17] Ramesh, P.; Subbiahpandi, A.; Manikannan, R.; Muthusu-
bramanian, S.; Ponnuswamy, M. N. Acta Cryst 2008, E64, o2243.
[18] Ramesh, P.; Subbiahpandi, A.; Manikannan, R.; Muthusu-
bramanian, S.; Ponnuswamy, M. N. Acta Cryst 2008, E64, o1889.
[19] Cacchi, S.; Fabrizi, G.; Carangio, A. Synlett 1997, 959.
[20] Rappoport, Z.; Gazit, A. J Org Chem 1986, 51, 4112.
[21] Lebedev, A. V.; Lebedeva, A. B.; Sheludyakov, V. D.;
Kovaleva, E. A.; Ustinova, O. L.; Kozhevnikov, I. B. Russ J Gen
Chem 2005, 75, 782.
3-(4-Nitrophenyl)-1H-pyrazole-4-carbaldehyde (7e). This
compound was obtained as white solid (Dichloromethane), mp
189–190 (198–200)ꢀC [19, 21]; 1H-NMR (CDCl3, 300 MHz):
d 8.00 (d, J ¼ 8.4 Hz, 2H), 8.26–8.29 (m, 3H), 9.98 (s, 1H).
[22] Prim, D.; Joseph, D.; Kirsch, G. Phosphorus Sulfur Silicon
Relat Elem 1994, 91, 137.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet