Synthesis of thiophenes, azoles and azines with potential biological activity by employing the versatile heterocyclic precursor N- benzoycyanoacetylhydrazine

Article abstract of DOI:10.1002/jccs.200700152

This research work is concerned with the use of N-benzoyl cyanoacetylhydrazine (3) in synthesizing several new heterocyclic compounds with potential biological activity, via its reaction with various chemical reagents. The synthesized derivatives have act

Full text of DOI:10.1002/jccs.200700152

Journal of the Chinese Chemical Society, 2007, 54, 1053-1066
1053
Synthesis of Thiophenes, Azoles and Azines with Potential Biological
Activity by Employing the Versatile Heterocyclic Precursor
N-Benzoycyanoacetylhydrazine
Rafat M. Mohareb,a* Jonathan Z. Hob and Fatma O. Alfarouka
aDepartment of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt
bMerck & Co., Inc., P.O. Box 2000, RY80R-164, 126 East Lincoln Avenue, Rahway, NJ 07065, USA
This research work is concerned with the use of N-benzoyl cyanoacetylhydrazine (3) in synthesizing
several new heterocyclic compounds with potential biological activity, via its reaction with various chem-
ical reagents. The synthesized derivatives have actually exhibited, upon screening, antibacterial and
antifungal activities.
Keywords: N-Benzoylhydrazide; Thiophene; Thiazole; Coumarin.
INTRODUCTION
Our continuous interest in the chemistry of hydra-
the reaction of an ethanol solution of cyanoacetyl hydra-
zine (1) with benzoyl chloride (2) in an ice bath with a tem-
perature range of 0-5 °C.
zones and hydrazides1-4 originates from our persistent trials
to obtain pyridines, pyrimidines, pyridazines, thiophenes
and their analogues. The importance of such compounds
lies in their diverse pharmaceutical activities, namely anti-
bacterial,5,6 antidiabetic,7 anti-HIV,8 antiviral9,10 and anal-
gesic activities. To our knowledge, little work has been
published on using N-benzoylcyanoacetyl hydrazine in
heterocyclic synthesis. In this work we report the use of the
title reagent in several heterocyclic transformations to ob-
tain pyrazole, pyridine, pyridazine, thiophene and triazine
derivatives of biological activity. N-benzoylcyanoacetyl
hydrazine synthesis was previously reported in the litera-
ture;11 however, we herein present a different and simple
method of its preparation using cyanoacetylhydrazine (1)
and benzoyl chloride (2).
Compound 3 reacts with benzaldehyde (4a), p-chlo-
robenzaldehyde (4b), or p-anisaldehyde (4c) in an ethanol
solution in the presence of a catalytic amount of piperidine
to give the benzal derivatives 5a-c, respectively.
The reactivity of the benzal derivative 5a towards
some chemical reagents was studied aiming at the forma-
tion of polyfunctionally substituted heterocyclic com-
pounds with potential biological activities. Thus, the reac-
tion of 5a with either malononitrile (6a) or ethyl cyano-
acetate (6b) gave the pyridine derivatives 7a and 7b, re-
spectively. The formation of compounds 7a and 7b is most
likely to proceed via Michael addition followed by cycliza-
tion. Structures of the latter products were based on analyti-
cal and spectral data. Thus, the 13C NMR spectrum of 7a
showed the presence of signals at d 120.2, 123.4, 128.5,
130.2, 133.9, 138.1, 139.6, 140.0, and 156.6 corresponding
to two C6H5 groups and the pyridine carbons, 115.6, 118.3
two CN groups and 160.2, 166.9 corresponding to two C=O
groups. On the other hand, the reaction of 5a with either
hydrazine hydrate (8a) or phenylhydrazine (8b) gave the
RESULTS AND DISCUSSION
Benzoyl cyanoacetylhydrazine (3) was prepared via
O
O
C
O
C
O
Ethanol
Ice bath
H2C
CN
C
NH
NH2
+
Ph
H2C
CN
NH
NH
Ph
C
Cl
2
3
1
* Corresponding author. E-mail: raafat_mohareb@yahoo.com

1054 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mohareb et al.
CN
C
O
C
O
C
Piperidine
H
N
3
+
X
CHO
NH
Ph
1,4-dioxane
CH
4a, X= H
b, X= p-Cl
c, X= p-OCH3
X
5a, X= H
b, X= p-Cl
c, X= p-OCH3
pyrazole derivatives 9a and 9b, respectively.
diazonium salts is studied aiming at the formation of hydra-
zones capable of heterocyclization. Thus the reaction of 3
with either benzenediazonium chloride (12a), p-chloro-
benzenediazonium chloride (12b), p-tolyldiazonium chlo-
ride (12c), or the diazonium acetates of 2-diazo-3-cyano-
4,5,6,7-tetrahydrobenzo[b]thiophene (12d) and ethyl 2-di-
azo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate
On the other hand, the reaction of 3 with salicalde-
hyde (10) gave the coumarin derivative 11. Formation of
similar coumarins through the reaction of cyanomethylene
reagents with salicylaldehyde has been previously re-
ported.12
The reaction of 3 with aromatic or heteroaromatic
O
O
NC
NH
C
Ph
N
X
H2C
5a
+
CN
Ph
NH2
6a, X= CN
b, X= COOC2H5
X
7a, X= CN
b, X= COOC2H5
O
C
O
C
Ph
NH
NH
Ph
5a
R
NH
NH2
+
R
N
NH2
N
8a, R= H
b, R= Ph
9a, R= H
b, R= Ph

N-Benzoyl Hydrazine in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1055
O
C
O
C
CHO
NH
NH
Ph
Ethanol
Piperidine,
3
+
Reflux
OH
O
O
11
10
(12e), gave the corresponding hydrazone derivatives 13a-e.
The 1H NMR spectrum of 13a (as an example) showed
a multiplet at d 7.21-7.57 ppm due to two phenyl groups
and three singlets (D2O exchangeable) at d 8.22, 8.29 and
9.41 ppm due to the three NH groups. The reaction of 13a
with either hydrazine hydrate (8a) or phenylhydrazine (8b)
gave the pyrazole derivatives 15a and 15b, respectively.
Formation of the latter products takes place supposedly
through the intermediate formation of the amidrazone de-
rivatives 14a and 14b, followed by water elimination. Ele-
mental and spectral analyses were consistent with the pro-
posed structures (see experimental section).
Structures of the products were based on analytical
and spectral data. Thus the 1H NMR spectrum of 20a showed
a singlet at d 5.36 ppm (D2O exchangeable) due to the
amino group, a multiplet at d 7.30-7.38 ppm due to the two
phenyl groups, and two singlets at d 8.49 and 8.81 ppm
(D2O exchangeable) due to the two NH groups.
The scope and limitation of using N-benzoylcyano-
acetyl hydrazine in forming condensed molecules were
also studied. Thus the reaction of 3 with acetophenone (21)
was carried out in the presence of ammonium acetate and
gave the condensate 22.
The 1H NMR of 22 exhibited a singlet at d 2.38 ppm
for the methyl group, two multiplets at d 7.31-7.38 ppm due
to the two phenyl groups and two singlets (D2O exchange-
able) at d 8.22 and 8.36 ppm for the two NH groups. Further
confirmation for the structure of 22 was achieved through
exploring its reactivity towards some chemical reagents.
Thus, the reaction of compound 22 with sulfur in DMF con-
taining triethylamine gave the thiophene derivative 23. An-
alytical and spectral data were in agreement with the pro-
posed structure (see experimental data).
Moreover, the reaction of 13a with phenyl isothio-
cyanate 16 gave the 1,2,4-triazine derivative 18 which is
presumably formed via the intermediate formation of 17.
Analytical and spectral data of the reaction product were in
agreement with the proposed structure.
On the other hand, the reaction of 13a with either
malononitrile (6a) or ethyl cyanoacetate (6b) gave the pyri-
dazine derivatives 20a and 20b, respectively. The reaction
presumably took place via the intermediate formation of
19a and 19b, respectively.
Moreover, the reaction of 22 with benzaldehyde (4a)
-
+
N
NCl
R
3
+
R
NH
N
C
C
O
NH
NH
C
O
Ph
CN
13a, R= Ph
12a, R= Ph
b, R= p-Cl-Ar
b, R= p-Cl-Ar
c, R= p-CH3-Ar
c, R= p-CH3-Ar
CN
CN
S
S
d, R=
e, R=
d, R=
e, R=
COOEt
COOEt
S
S

1056 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mohareb et al.
+
R
NH
NH2
Ph
NH
N
C
C
O
NH
NH
C
O
Ph
CN
8a, R= H
b, R= Ph
13a
Ph
NH
N
C
C
N
NH
C
O
Ph
OH
NH
H2N
N
R
14a, R= H
b, R= Ph
-H2O
O
Ph
HN
N
N
NH
C
Ph
N
R
H2N
N
15a, R= H
b, R= Ph
gave the benzal derivative 24, and with benzenediazonium
chloride (12a) gave the hydrazone derivative 25.
methylene reagents with phenyl isothiocyanate in a basic
dimethylformamide solution, followed by heterocycliza-
tion with a-halocarbonyl compounds.13-18 The reaction
leads to the formation of either thiophene or thiazole deriv-
atives depending on the reaction conditions and the nature
of the a-halocarbonyl compound. In continuation of this
work, compound 3 has been subjected to the Hantzsch reac-
tion, and it was found that it reacts with phenylisothiocya-
nate (16) in a solution of dimethylformamide and potas-
sium hydroxide to give the non-isolable potassium sulfide
salt 28, which reacts with ethyl chloroacetate (29a) or
methyl bromoacetate (29b) to give in each case a single
product with a molecular formula C21H20N4SO4 and
C20H18N4SO4, respectively. Two possible isomeric prod-
ucts were considered: either 30a,b or 31a,b.
In addition, the reaction of 22 with either malono-
nitrile (6a) or ethyl cyanoacetate (6b) gave the polyfunc-
tionally substituted benzene derivatives 27a and 27b, re-
spectively. The proposed structures for the latter products
were in agreement with their analytical and spectral data.
Thus, the 1H NMR spectrum of 27a showed two singlets at
d 4.48 and 5.62 ppm (D2O exchangeable) for the two amino
groups, two singlets at d 8.68 and 9.41 ppm (D2O ex-
changeable) for the two NH groups, and a multiplet at d
7.26-7.39 ppm due to eleven aromatic protons present in
the two phenyl groups and in the parent benzene ring.
In recent years, our research group was involved in a
comprehensive program dealing with the reaction of active

N-Benzoyl Hydrazine in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1057
By following the same procedure, the non-isolable in-
termediate potassium salt 28 was also reacted with chloro-
acetone (32) and gave the thiophene derivative 33.
In a similar manner, 28 reacted with w-bromoaceto-
phenone 34 to yield the thiophene derivative 35.
The reactivity of compound 3 towards cinnamonitrile
derivatives was also studied. Thus 3 was reacted with the
cinnamonitrile derivatives 36a-d to give in each case a
single product with a molecular formula C20H13N5O2,
C22H18N4O4, C21H15N5O3 and C23H20N4O5, respectively.
Further confirmation for the latter structures was
achieved through an alternative synthesis. Thus, the prod-
ucts 7a,b were previously obtained via the reaction of 5a
with malononitrile (6a) and ethyl cyanoacetate (6b), re-
spectively. Similarly, compounds 38a,b were alternatively
synthesized through reacting the benzal derivative 5c with
6a and 6b, respectively.
SCREENING FOR ANTIMICROBIAL ACTIVITY
Twenty-one compounds were screened in vitro for
their antimicrobial activity against two bacterial isolates,
one saprophytic (Escherichia coli) and the other is parasitic
(Xanthomonas citi) and 3 fungal isolates one saprophytic
(Aspergillus fumigatus) and two phytopathogenic (Rhizo-
ctonia solani and Fusarium oxysporum). The culture me-
dium was the nutrient agar for bacteria and Czapek’s Dox
agar medium for fungi. The sterile medium was inoculated
with the test organism so that each 100 mL of the medium
received 1 mL of a 24 hour culture of the bacterium or 7-
day-old culture of spore suspension of the fungus. The so-
lutions of the tested compounds at 25 µg/mL in dimethyl-
formamide (DMF) were placed separately in the cup (8 mm
diameter). The plates were incubated at 28 ºC and the re-
sulting inhibition zones were measured. DMF as a blank
exhibited no antimicrobial activity against any of the tested
organisms used. The recorded inhibition zones are summa-
rized in Table 1. The results indicated that most of the pre-
pared compounds are active against the test organisms. The
most toxic compounds against bacterial and fungal isolates
were 15a, 15b, 18, 7a and 38d, followed by 5b, 5c, 11,
13a-c, 13e, and 20a,b. Compounds 13d, 25 and 27a and
27b were less toxic to the test organisms. In general, bacte-
rial isolates were more susceptible to the synthesized com-
pounds than fungal isolate.
The IR spectrum of the product was in favor of the
thiophenes 31a,b due to the absence of any cyano group
stretching which is expected to appear in the range of 2210-
2227 cm-1, and the appearance of an amino group stretching
in the range of 3480-3370 cm-1 instead. Moreover, the 1H
NMR spectrum showed in the case of 31b, a singlet at d
2.82 ppm for the methyl group, a multiplet at d 7.28-7.35
ppm for the two phenyl groups and three singlets (D2O ex-
changeable) at d 8.30, 8.45 and 8.47 ppm for the three NH
groups.

1058 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mohareb et al.
O
C
O
C
CN
H
N
H
N
Ph
HN
N
C
Ph
H2C
13a
+
X
X
NH2
6a, X= CN
b, X= COOEt
NC
19a, X= CN
b, X= COOEt
O
O
C
N
H
N
Ph
N
N
H
Ph
Y
NH2
CN
20a, Y= NH
b, Y= O
EXPERIMENTAL
units of ppm. Analytical data were obtained from the Micro
Analytical Data Unit at Cairo University and UC Berkeley,
California State University, USA.
All melting points were determined in open capillar-
ies and are uncorrected. IR spectra were measured using
KBr discs on a Pye Unicam SP-1000 spectrophotometer.
1H-NMR spectra were measured on a Varian EM390-200
MHz instrument in CD3SOCD3 as solvent using TMS as in-
ternal standard, and chemical shifts are expressed as d in
N-Benzoylcyanoacetylhydrazine (3)
In an ice bath (0-5 oC), benzoyl chloride (11.6 g, 0.08
mol) is added dropwise to an ethanol solution of cyano-
acetylhydrazine (8.20 g, 0.08 mol), with continuous stir-
O
O
C
O
C
H
N
H
N
Ammonium acetate
140 oC
NC
Ph
C
Ph
3
+
Ph
CH3
CH3
21
22
CO
NH
NH
C
Ph
Ph
O
Et3N
DMF
S
22
+
NH2
S
23

N-Benzoyl Hydrazine in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1059
O
O
C
NC
Ph
H
N
H
N
C
C
Ph
Piperidine
Ethanol
22
+
4a
C
H
CH Ph
24
O
C
O
NC
Ph
H
N
H
N
EtOH
C
C
Ph
22
+
12a
NaOAc
C
H
N
NH Ph
25
O
O
NC
Ph
H
N
H
N
CN
C
C
C
Ph
22
+
H2C
X
NH2
6a, X= CN
b, X= COOEt
X
26
NH2
O
O
X
NH NH
C
Ph
H2N
Ph
27a, X= CN
b, X= COOEt
ring. The compound in question precipitates immediately
and is collected by filtration. The analytical and spectral
data of this compound are analogous with those reported in
the literature. White crystals from ethanol, yield 80.05%,
13 g, m.p. 165 oC.
mixture and the solid product collected by filtration and
recrystallized from the proper solvent.
N-Benzoyl-a-benzalcyanoacetylhydrazine (5a)
Yellowish white crystals from ethanol, yield 57.60%,
3.3 g, m.p. 110 °C. IR (KBr): u/cm-1 = 3460-3310 (2 NH),
3062 (CH aromatic), 2225 (CN), 1700, 1680 (2 C=O), 1635
(C=C). 1H NMR (DMSO) d = 6.80 (CH=C), 7.21-7.38 (m,
10H, 2 C6H5), 8.32, 8.75 (2s, 2H, 2NH). C17H13N3O2
(291.31): Calcd: C, 70.09; H, 4.50; N, 14.43%; Found: C,
70.22; H, 4.77; N, 14.60%.
Synthesis of 5a-c (General Procedure)
Equimolar amounts (0.019 mol) of N-benzoylcyano-
acetylhydrazine 3 and 4a, 4b or 4c, in ethanol containing a
catalytic amount of piperidine, were heated under reflux
for 2 h. The reaction mixture was poured on an ice-water

1060 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mohareb et al.
O
C
O
C
NC
H
N
H
N
DMF
C
Ph
3
+
16
KOH
-
+
SK
Ph
N
H
28
O
C
O
C
NC
H
N
H
N
C
Ph
Ph
N
H
S
CH2
C
OR
O
X
28
+
H2C
30a, R= Et
COOR
b, R= CH3
O
O
C
H2N
29a, X= Cl, R= C2H5
b, X= Br, R= CH3
N
H
NH
Ph
RO
N
H
Ph
S
O
31a, R= Et
b, R= CH3
N-Benzoyl-a-(4-chlorobenzal)cyanoacetylhydrazine
(325.76): Calcd: C, 62.68; H, 3.71; N, 12.90%; Found: C,
62.70; H, 3.92; N, 12.65%.
(5b)
Yellow crystals from ethanol, yield 64.92%, 5.2 g,
m.p. 145 ºC. IR (KBr): u/cm-1 = 3444-3320 (2 NH), 3058
(CH aromatic), 2227 (CN), 1695, 1680 (2 C=O), 1638
(C=C). 1H NMR (DMSO) d = 6.75 (CH=C), 7.32-7.40 (m,
9H, C6H5, C6H4), 8.30, 8.69 (2 s, 2H, 2NH). C17H12N3O2Cl
N-Benzoyl-a-(4-methoxybenzal)cyanoacetylhydrazine
(5c)
Pale yellow crystals from ethanol, yield 94.86%, 1.2
g, m.p. 130 ºC. IR (KBr): u/cm-1 = 3435-3318 (2NH), 3050
O
O
H2N
O
NH
NH
C
Ph
28
+
Cl
CH2
C
CH3
H3C
N
H
Ph
S
32
O
33
O
O
O
H2N
NH
NH
C
Ph
28
+
Ph
C
CH2
Br
Ph
N
H
Ph
34
S
O
35

N-Benzoyl Hydrazine in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1061
O
C
O
C
NC
H
N
H
N
CN
X
CH
CH
Ph
3
+
R
CH
C
CN
X
CH
37
36a, R = H, X =CN
b, R = H, X = COOC2H5
c, R = p-OCH3, X = CN
d, R = p-OCH3, X = COOC2H5
R
O
O
NC
H
N
N
C
Ph
CN
O
O
CN
X
NH2
H
N
C
C
NH
C
Ph
+
H2C
X
CH
R
6a, X= CN
b, X= COOEt
7a, R = H, X =CN
b, R = H, X = COOC2H5
38a, R = p-OCH3, X = CN
b, R = p-OCH3, X = COOC2H5
X
5a, X= H
c, X= p-OCH3
1
(CH aromatic), 2975 (CH3), 2220 (CN), 1698, 1683 (2C=O),
1640 (C=C). 1H NMR (DMSO) d = 3.21 (s, 3H, CH3), 6.80
(s, 1H, CH=C), 7.31-7.39 (m, 9H, C6H5, C6H4), 8.21, 8.30
(2s, 2H, 2NH). C18H15N3O3 (321.34): Calcd: C, 67.28; H,
4.71; N, 13.08%; Found: C, 67.50; H, 5.31; N, 13.50%.
1640 (C=C). H NMR (DMSO) d = 4.88 (s, 2H, NH2),
7.29-7.36 (m, 10H, 2 C6H5), 8.43 (s, br, 1H, NH). 13C NMR
d 120.2, 123.4, 128.5, 130.2, 133.9, 138.1, 139.6, 140.0,
156.6 (2C6H5), 115.6, 118.3 (2 CN), 160.2, 166.9 (2 CO).
C20H13N5O2 (355.36): Calcd: C, 67.60; H, 3.69; N, 19.71%;
Found: C, 67.90; H, 4.10; N, 19.95%.
Synthesis of 7a,b (General Procedure)
Equimolar amounts of N-benzoyl-a-benzalcyano-
acetylhydrazine (5a) (1.72 ´ 10-3 mol) and either 6a or 6b
in ethanol containing a catalytic amount of triethylamine (a
few drops), were heated under reflux for 3 h. The reaction
mixture was then poured over an ice-water mixture and
treated with a few drops of HCl. The solid product was col-
lected by filtration and recrystallized from ethanol.
Ethyl 2-amino-1-benzamino-5-cyano-6-oxo-4-phenyl-
pyridine-3-carboxylate (7b)
Grey crystals from ethanol, yield 54.55%, 0.30 g,
m.p. 130 ºC. IR (KBr): u/cm-1 = 3495-3360 (NH2, 3NH),
3050 (CH aromatic), 2975, 2870 (3C=O), 1640 (C=C). 1H
NMR (DMSO) d = 1.15 (t, 3H, J = 7.05 Hz, CH3), 4.24 (q,
2H, J = 7.05 Hz, CH2), 5.21 (s, 2H, NH2), 7.31-7.38 (m,
10H, 2 C6H5), 8.81 (s, 1H, NH). C22H18N4O4 (402.41):
Calcd: C, 65.67; H, 4.51; N, 13.92%; Found: C, 66.15; H,
4.45; N, 14.40%.
2-Amino-1-benzamino-3,5-dicyano-6-oxo-5-phenylpyri-
dine (7a)
Yellowish brown crystals from ethanol, yield 58.33%,
0.35 g, m.p. 170 ºC. IR (KBr): u/cm-1 = 3565-3348 (NH2,
NH), 3054 (CH aromatic), 2222 (2CN), 1688, 1684 (2C=C),
Preparation of 9a,b (General Procedure)
To a solution of N-benzoyl-a-benzalcyanoacetylhy-

1062 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mohareb et al.
Table 1. Inhibition zones in mm for some of the synthesized compounds at a concentration
level of 25 mg/mL
Compound
E. coli
X. citri
A. fumigatus
R. solani
F. oxysporum
5b
26
22
30
32
14
13
24
23
10
14
34
26
32
28
10
18
22
10
18
26
37
26
18
36
15
10
12
18
16
10
12
30
24
29
26
8
12
10
32
12
8
13
14
18
4
14
18
16
0
5c
7a
7b
11
9
8
13a
13b
13c
13d
13e
15a
15b
18
6
5
4
16
16
6
13
14
8
17
19
0
8
4
4
18
16
17
19
6
14
15
16
17
0
18
13
18
13
4
20a
20b
25
12
16
29
22
33
18
6
5
0
27a
27b
31a
33
5
3
0
30
18
28
16
15
6
18
4
16
15
17
16
38d
drazine (5a) (1.58 ´ 10-3 mol) in ethanol, an equimolar
amount of 8a or 8b is added and the solution is heated under
reflux for 3 h, after which the contents are poured on an
ice-water mixture and the precipitated solid is then filtered
out and recrystallized from ethanol.
NH2), 7.26-7.36 (m, 15H, 3C6H5), 8.22, 9.26 (2s, 2H,
2NH). C23H19N5O2 (397.44): Calcd: C, 69.51; H, 4.82; N,
17.62%; Found: C, 70.10; H, 4.35; N, 17.00%.
Synthesis of 11
To a solution of N-benzoylcyanoacetylhydrazine 3
(0.6 g, 2.96 ´ 10-3 mol) in ethanol, a few drops of piperidine
are added, followed by the addition of salicylaldehyde (10)
(0.36 g, 2.96 ´ 10-3 mol). The reaction mixture is then
heated under reflux for 3 h, after which it is poured on an
ice-water mixture. The precipitated crystals are then col-
lected by filtration and recrystallized from ethanol.
5-Amino-4-N-benzoylhydrazido-3-phenyl-pyrazole
(9a)
Pale brown crystals from ethanol, yield 54.90%, 0.28
g, m.p. 145 ºC. IR (KBr): u/cm-1 = 3466-3312 (NH2, 3 NH),
3060 (CH aromatic), 1690, 1685 (2 C=O), 1660 (C=N),
1
1640 (C=C). H NMR (DMSO) d = 5.42 (s, 2H, NH2),
7.31-7.40 (m, 10H, 2C6H5), 8.20, 9.23, 9.40 (3s, 3H, 3NH).
13C NMR d 124.5, 127.5, 127.5, 132.2, 134.2, 154.2 (two
C6H5, pyrazole), 163.8, 168.4 (2 CO). C17H15N5O2 (321.34):
Calcd: C, 63.54; H, 4.71; N, 21.80%; Found: C, 63.70; H,
4.90; N, 21.35%.
3-(N-benzoylhydrazido)-coumarin (11)
Orange crystals from ethanol, yield 54.95%, 0.5 g,
m.p. 60 ºC. IR (KBr): u/cm-1 = 3420-3310 (2NH), 3054
(CH aromatic), 1690, 1682 (2C=O), 1640 (C=C). 1H NMR
(DMSO) d = 6.82 (s, 1H, coumarin H-4), 7.33-7.41 (m, 9H,
C6H5, C6H4), 8.22, 8.30 (2s, 2H, 2NH). C17H12N2O4 (308.30):
Calcd: C, 66.23; H, 3.92; N, 9.09%; Found: C, 66.58; H,
4.23; N, 9.60%.
5-Amino-4-N-benzoylhydrazido-2,3-diphenylpyrazole
(9b)
Yellowish brown crystals from ethanol, yield 70.59%,
0.48 g, m.p. 107 ºC. IR (KBr): u/cm-1 = 3473-3318 (NH2, 2
NH), 3063 (CH aromatic), 1688, 1685 (2 C=O), 1654
Synthesis of 13a-e (General Procedure)
1
(C=N), 1638 (C=C). H-NMR (DMSO) d = 5.38 (s, 2H,
To a cold (0-5 ºC) solution of compound 3 (4.25 g,

N-Benzoyl Hydrazine in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1063
0.02 mol) in ethanol, containing a few sodium hydroxide
pellets, an equimolar amount of any of compounds 12a-e
[prepared by adding an aqueous sodium nitrite solution
(2.9 g, 0.04 mol) to a cold solution of either aniline, p-
chloroaniline, p-toluidine, 2-amino-3-cyano-4,5,6,7-tetra-
hydrobenzo[b]thiophene or 2-amino-3-ethoxycarbonyl-
4,5,6,7-tetrahydrobenzo[b]thiophene, respectively, in the
appropriate amount of conc. HCl at 0-5 ºC, with continuous
stirring] was added with stirring. The reaction mixture was
left at room temperature for an additional hour, then the
formed solid product was filtered out and recrystallized
from ethanol.
g, m.p. 140 ºC. IR (KBr): u/cm-1 = 3468-3341 (3NH), 3060
(CH aromatic), 2225, 2220 (2 CN), 1684, 1680 (2C=O),
1663 (C=N), 1640 (C=C). 1H NMR (DMSO) d = 2.24-2.27
(m, 4H, 2CH2), 2.32-3.35 (m, 4H, 2CH2), 7.32-7.36 (m,
5H, C6H5), 8.30, 8.32-8.34 (3s, 3H, 3NH). C19H16N6O2S
(392.44): Calcd: C, 58.15; H, 4.11; N, 21.42; S, 8.17%;
Found: C, 58.40; H, 4.24; N, 22.00; S, 8.65%.
a-(3-Ethoxycarbonyl-2-hydrazo-4,5,6,7-tetrahydroben-
zo[b]thieno)-N-benzoylcyanoacetylhydrazine (13e)
Dark brown crystals from ethanol, yield 40.82%, 0.40
g, m.p. 180 ºC. IR (KBr): u/cm-1 = 3465-3325 (3NH), 3054
(CH aromatic), 2985, 2875 (CH3, CH2), 2222 (CN), 1695,
1684 (3C=O), 1656 (C=N), 1633 (C=C). 1H NMR (DMSO)
d = 1.16 (t, 3H, J = 7.45 Hz, CH3), 2.24-2.26 (m, 4H,
2CH2), 2.33-2.36 (m, 4H, 2CH2), 4.24 (q, 2H, J = 7.45 Hz,
CH2), 7.32-7.38 (m, 5H, C6H5), 8.28, 8.32, 8.34 (3s, 3H,
3NH). C21H21N5O4S (439.50): Calcd: C, 57.39; H, 4.82; N,
15.94; S, 7.30%; Found: C, 57.93; H, 4.33; N, 15.80; S,
7.02%.
a-Phenylhydrazo-N-benzoyl cyanoacetylhydrazine
(13a)
Reddish orange crystals from ethanol, yield 58.94%,
3.79 g, m.p. 195 ºC. IR (KBr): u/cm-1 = 3480-3328 (3NH),
3062 (CH aromatic), 2228 (CN), 1688, 1680 (2C=O), 1660
(C=N), 1635 (C=C). 1H NMR (DMSO) d = 7.21-7.57 (m,
10H, 2C6H5), 8.27, 8.29, 9.41 (3s, 3H, 3NH). C16H13N5O2
(307.32): Calcd: C, 62.54; H, 4.26; N, 22.79%. Found: C,
62.90; H, 4.40; N, 23.25%.
Preparation of 15a,b (General Procedure)
To a solution of 13a (1.30 ´ 10-3 mol) in ethanol, an
equimolar amount of either 8a or 8b is added. The reaction
mixture is then heated under reflux for 4 h, after which it is
poured on an ice-water mixture and the resulting precipi-
tate collected by filtration and recrystallized from ethanol.
a-(4-Chloro-phenylhydrazo)-N-benzoylcyanoacetylhy-
drazine (13b)
Light brown crystals from ethanol, yield 41.67%,
0.35 g, m.p. 120 ºC. IR (KBr): u/cm-1 = 3475-3340 (3NH),
3054 (CH aromatic), 2225 (CN), 1686, 1680 (2C=O), 1670
(C=N), 1634 (C=C). 1H NMR (DMSO) d = 7.26-7.34 (m,
9H, C6H5, C6H4), 8.29-8.34 (m, 3H, 3NH). C16H12N5O2Cl
(341.76): Calcd: C, 56.23; H, 3.54; N, 20.49%; Found: C,
56.09; H, 4.15; N, 19.88%.
5-Amino-3-benzoylhydrazono-4-phenylhydrazonopyr-
azole (15a)
Brick red crystals, yield 59.52%, 0.25 g, m.p. 105 ºC.
IR (KBr): u/cm-1 = 3492-3354 (NH2, 3NH), 3060 (CH aro-
matic), 1670 (C=N), 1637 (C=C). 1H NMR (DMSO) d =
4.48 (s, 2H, NH2), 7.32-7.41 (m, 10H, 2C6H5), 8.09, 8.43,
8.98 (3s, 3H, 3NH). 13C NMR d 116.3, 118.6, 120.5, 128.9,
129.2, 130.1, 133.4 (2 C6H5), 153.3, 154.1, 154.5 (3 C=N),
164.0 (C=O). (321.35): Calcd: C, 59.80; H, 4.71; N,
30.51%. Found: C, 60.21; H, 4.58; N, 30.15%.
a-(4-Methyl-phenyl hydrazo)-N-benzoylcyanoacetyl-
hydrazine (13c)
Orange crystals from ethanol, yield 84.91%, 2.70 g,
m.p. 125 ºC. IR (KBr): u/cm-1 = 3478-3336 (3NH), 3058
(CH aromatic), 2980 (CH3), 2228 (CN), 1690, 1683 (2C=O),
1665 (C=N), 1634 (C=C). 1H NMR (DMSO) d = 2.88 (s,
3H, CH3), 7.32-7.39 (m, 9H, C6H5, C6H4), 8.30-8.34 (m,
3H, 3NH). C17H15N5O2 (321.34): Calcd: C, 63.54; H, 4.71;
N, 21.80%; Found: C, 64.12; H, 4.55; N, 21.35%.
5-Amino-3-benzoylhydrazono-2-phenyl-4-phenylhy-
drazonopyrazole (15b)
Yellowish brown crystals, yield 58.82%, 0.3 g, m.p.
68 ºC. IR (KBr): u/cm-1 = 3488-3305 (NH2, 2NH), 3057
(CH aromatic), 1670 (C=N), 1640 (C=C). 1H NMR (DMSO)
d = 4.91 (s, 2H, NH2), 7.28-7.36 (m, 15H, 3C6H5), 8.30,
8.78 (2s, 2H, 2NH). C22H19N7O (397.44): Calcd: C, 66.49;
a-(3-Cyano-2-hydrazo-4,5,6,7-tetrahydrobenzo[b]-
thieno)-N-benzoyl cyanoacetylhydrazine (13d)
Dark brown crystals from ethanol, yield 47.27%, 0.52

1064 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mohareb et al.
H, 4.82; N, 24.67%. Found: C, 67.01; H, 4.69; N, 24.48%.
treated with ethanol and subsequently with ice and water
after which the formed solid is collected by filtration.
Synthesis of 18 and 20a,b (General Procedure)
To a solution of 13a (0.5 g, 1.63 ´ 10-3 mol) in etha-
nol, a few drops of triethylamine are added, followed by the
introduction of an equimolar amount of phenylisothio-
cyanate (16), malononitrile 6a or ethyl cyanoacetate 6b.
The contents are then heated under reflux for 3 h, after
which they are left to cool down at room temperature; a few
drops of diethyl ether are added, and the solvents are evap-
orated under a vacuum. The precipitate is then air-dried.
$-Phenyl-a-(N-benzoylhydrazido)-crotononitrile (22)
Pale yellow crystals from ethanol, yield 44%, 0.33 g,
m.p. 80 ºC. IR (KBr): u/cm-1 = 3460-3350 (2NH), 3050
(CH aromatic), 2220 (CN), 1688, 1679 (2C=O), 1640
(C=C). 1H NMR (DMSO) d = 2.38 (s, 3H, CH3), 7.21-7.38
(m, 10H, 2C6H5), 8.22, 8.36-8.38 (2s, 2H, 2NH). C18H15N3O2
(305.34): Calcd: C, 70.81; H, 4.95; N, 13.76%. Found: C,
71.23; H, 5.24; N, 14.14%.
6-N-benzoylhydrazido-5-imino-2,4-diphenyl-3-thioxo-
1,2,4-triazine (18)
2-Amino-3-N-benzoylhydrazido-4-phenylthiophene
(23)
Reddish black crystals, yield 52.78%, 0.38 g, m.p. 45
ºC. IR (KBr): u/cm-1 = 3460-3342 (3NH), 3063 (CH aro-
1
matic), 1660 (C=N), 1637 (C=C), 1205-1193 (C=S). H
To a solution of 22 (0.5 g, 1.64 ´ 10-3 mol) in ethanol,
an equimolar amount of sulfur and a few drops of triethyl-
amine are added and the contents are heated under reflux
for 3 h. The reaction mixture is then poured on an ice-water
mixture and the precipitate filtered out.
NMR (DMSO) d = 7.28-7.36 (m, 15H, 3C6H5), 8.81-8.88
(m, 3H, 3NH). C23H18N6O2S (442.50): Calcd: C, 62.43; H,
4.10; N, 19.00; S, 7.25%; Found: C, 62.85; H, 4.37; N,
19.20; S, 6.95%.
Pale brown crystals from ethanol, yield 45.2%, 0.25
g, m.p. 85 ºC. IR (KBr): u/cm-1 = 3474-3310 (NH2, 3NH),
3055 (CH aromatic), 1693, 1686 (2C=O), 1665 (C=N),
1639 (C=C). 1H NMR (DMSO) d = 4.47 (s, 2H, NH2), 6.77
(s, 1H, thiophene H-5), 7.30-7.37 (m, 10H, 2C6H5), 8.27,
9.26 (2s, 2H, 2NH). C18H15N3O2S (337.40): Calcd: C,
64.08; H, 4.48; N, 12.45; S, 9.50%. Found: C, 64.37; H,
4.13; N, 12.89; S, 10.02%.
4-Amino-3-N-benzoylhydrazido-5-cyano-6-imino-1-
phenylpyridazine (20a)
Orange brown crystals from ethanol, yield 57.38%,
0.35 g, m.p. 85 ºC. IR (KBr): u/cm-1 = 3495-3309 (NH2,
3NH), 3058 (CH aromatic), 2222 (CN), 1673 (C=N), 1634
(C=C). 1H NMR (DMSO) d = 5.36 (s, 2H, NH2), 7.30-7.38
(m, 10H, 2C6H5), 8.32, 8.49, 8.81 (3s, 3H, 3NH). C19H15N7O2
(373.38): Calcd: C, 61.12; H, 4.05; N, 26.26%; Found: C,
60.76; H, 4.23; N, 26.48%.
$-Phenyl-(-benzal-a-(N-benzoylhydrazido)-crotono-
nitrile (24)
To a solution-containing a few drops of piperidine of
20 (0.12 g, 3.94 ´ 10-3 mol) in ethanol, benzaldehyde (4a)
(0.07 g, 3.94 ´ 10-3 mol) is added, and the solution is then
heated under reflux for 2.5 h, after which it is poured on an
ice-water mixture. The formed solid is then collected by fil-
tration.
4-Amino-3-N-benzoylhydrazido-5-cyano-6-oxo-1-phen-
ylpyridazine (20b)
Reddish crystals from ethanol, yield 51.02%, 0.25 g,
m.p. 55 ºC. IR (KBr): u/cm-1 = 3480-3312 (NH2, 2NH),
3054 (CH aromatic), 2220 (CN), 1688-1680 (3C=O), 1658
Yellowish brown crystals from ethanol, yield 75%,
1.16 g, m.p. 42 ºC. IR (KBr): u/cm-1 = 3445-3305 (2NH),
3052 (CH aromatic), 2218 (CN), 1686, 1680 (2C=O), 1637
(C=C). 1H NMR (DMSO) d = 6.36, 6.48 (2s, 2H, CH=CH),
7.28-7.36 (m, 15H, 3C6H5), 8.40, 8.43 (2s, 2H, 2NH).
C25H19N3O2 (393.45): Calcd: C, 76.32; H, 4.87; N, 10.68%.
Found: C, 75.82; H, 4.29; N, 10.30%.
1
(C=N), 1634 (C=C). H NMR (DMSO) d = 5.39 (s, 2H,
NH2), 7.26-7.34 (m, 10H, 2C6H5), 8.40, 8.81 (2s, 2H,
2NH). C19H14N6O3 (374.36): Calcd: C, 60.96; H, 3.77; N,
22.45%; Found: C, 61.56; H, 4.20; N, 22.01%.
Synthesis of 22
Equimolar amounts of 3 (0.5 g, 2.46 ´ 10-3 mol),
acetophenone 21 (0.3 g, 2.46 ´ 10-3 mol), and solid ammo-
nium acetate (a few granules), are fused at 150 ºC in an oil
bath for 1 h. The reactants are then left to cool down,
$-Phenyl-a-(N-benzoylhydrazido)-(-phenylhydrazo-
crotononitrile (25)
To a cold (0-5 ºC) solution of 22 (1 g, 3.28 ´ 10-3 mol)

N-Benzoyl Hydrazine in Heterocyclic Synthesis
J. Chin. Chem. Soc., Vol. 54, No. 4, 2007 1065
in ethanol, containing ammonium acetate, an equimolar
quantity of benzenediazonium chloride (12a) (0.46 g, 3.28
´ 10-3 mol) [prepared as previously described] is added,
with stirring. The precipitated solid is then filtered out.
Golden brown crystals from ethanol, yield 67.17%,
0.9 g, m.p. 55 ºC. IR (KBr): u/cm-1 = 3465, 3309 (3NH),
3065 (CH aromatic), 2218 (CN), 1686, 1675 (2C=O), 1655
(0.33 g, 2.46 ´ 10-3 mol) is then stirred in and the solution is
covered and left overnight. Equimolar amounts of either
ethyl chloroacetate (29a) or methyl bromoacetate (29b) are
stirred in (10 min) on the following day, and the solution is
covered for another night, after which the reaction mixture
is poured onto ice and the precipitated solid is filtered out.
1
(C=N), 1640 (C=C). H NMR (DMSO) d = 6.59 (s, 1H,
Ethyl 2-phenylamino-3-N-benzoylhydrazido-4-amino-
thiophene-5-carboxylate (31a)
CH=N), 7.26-7.36 (m, 15H, 3C6H5), 8.32, 8.84, 9.03 (3s,
3H, 3NH). C24H19N5O2 (397.44): Calcd: C, 70.40; H, 4.68;
N, 17.10%. Found: C, 70.90; H, 5.00; N, 17.50%.
Brown crystals from ethanol, yield 38.46%, 0.4 g,
m.p. 125 ºC. IR (KBr): u/cm-1 = 3480-3365 (NH2, 3NH),
3058 (CH aromatic), 2975, 2890, (CH3, CH2), 1690-1680
(3C=O), 1642 (C=C). 1H NMR (DMSO) d = 1.16 (t, 3H,
CH3), 4.24 (q, 2H, CH2), 5.02 (s, 2H, NH2), 7.32-7.38 (m,
10H, 2 C6H5), 8.29, 8.39-8.45 (3s, 3H, 3NH). C21H20N4O4S
(424.48): Calcd: C, 59.42; H, 4.75; N, 13.20%. Found: C,
59.63; H, 4.89; N, 13.57%.
Preparation of 27a,b
(General Procedure): To a solution of 22 (0.46 g, 1.51
´ 10-3 mol) in ethanol, containing a few drops of triethyl-
amine, an equimolar amount of either malononitrile (6a) or
ethyl cyanoacetate (6b) is added and all is heated under re-
flux for 4 h. The reaction mixture is then poured on an ice-
water mixture and the formed solid is then collected by fil-
tration.
Methyl 2-phenylamino-3-N-benzoylhydrazido-4-
amino-thiophene-5-carboxylate (31b)
Dark orange crystals from ethanol, yield 53%, 0.53 g,
m.p. 130 ºC. IR (KBr): u/cm-1 = 3475-3370 (NH2, 3NH),
3060 (CH aromatic), 2970 (CH3), 1694-1685 (3C=O),
1640 (C=C). 1H NMR (DMSO) d = 2.82 (s, 3H, CH3), 4.82
(s, 2H, NH2), 7.28-7.35 (m, 10H, 2C6H5), 8.30, 8.45-8.47
(3s, 3H, 3NH). C20H18N4O4S (410.46): Calcd: C, 58.53; H,
4.42; N, 13.65%. Found: C, 58.24; H, 4.38; N, 13.50%.
1,3-Diamino-2-cyano-5-phenyl-6-(N-benzoylhydrazido)-
benzene (27a)
Pale brown crystals from ethanol, yield 57.14%, 0.32
g, m.p. 70 ºC. IR (KBr): u/cm-1 = 3475-3325 (2NH2, 2NH),
3062 (CH aromatic), 2222 (CN), 1686 (C=O), 1640 (C=C).
1H NMR (DMSO) d = 4.48, 5.62 (2s, 4H, 2NH2), 7.26-7.39
(m, 11H, 2C6H5, C6H), 8.68, 9.41 (2s, 2H, 2NH). C21H17N5O2
(371.40): Calcd: C, 67.92; H, 4.61; N, 18.86%. Found: C,
67.57; H, 4.53; N, 18.66%.
Synthesis of 33 and 35
(General Procedure): Compound 3 (0.6 g, 2.96 ´ 10-3
mol) is dissolved in dimethylformamide, and a few sodium
hydroxide pellets are added. Phenylisothiocyanate (16)
(0.40 g, 2.96 ´ 10-3 mol) is then stirred in and the solution is
covered and left overnight. An equimolar amount of either
chloroacetone (32) or T-bromoacetophenone (34) is then
added and the solution is stirred for 10 minutes and left,
covered, for another night. The reaction mixture is then
poured onto an ice-water mixture and the formed solid is
filtered out.
Ethyl 1,3-diamino-5-phenyl-6-(N-benzoylhydrazido)-2-
carboxylate (27b)
Pale brown crystals from ethanol, yield 52.81%,
0.47g, m.p. 80 ºC. IR (KBr): u/cm-1 = 3510-3322 (2NH2,
2NH), 3052 (CH aromatic), 1692-1678 (3C=O), 1638
(C=C). 1H NMR (DMSO) d = 1.15 (t, 3H, CH3), 4.26 (q,
2H, CH2), 4.52, 5.63 (2s, 4H, 2NH2), 7.28-7.40 (m, 11H,
2C6H5, C6H), 8.43, 9.21 (2s, 2H, 2NH). C23H22N4O4
(418.46): Calcd: C, 66.02; H, 5.30; N, 13.39%. Found: C,
66.33; H, 5.64; N, 13.83%.
5-Acetyl-4-amino-3-N-benzoylhydrazido-2-phenyl-
aminothiophene (33)
Synthesis of 31a,b
Dark brown crystals from ethanol, yield 30%, 0.35 g,
m.p. 100 ºC. IR (KBr): u/cm-1 = 3460-3335 (NH2, 3NH),
3052 (CH aromatic), 2970 (CH3), 1686-1678 (3C=O),
1640 (C=O). 1H NMR (DMSO) d = 3.26 (s, 3H, CH3), 4.88
(General Procedure): Compound 3 (0.5 g, 2.46 ´ 10-3
mol) is dissolved in dimethylformamide and a few sodium
hydroxide pellets are added. Phenyl isothiocyanate (16)

1066 J. Chin. Chem. Soc., Vol. 54, No. 4, 2007
Mohareb et al.
(s, 2H, NH2), 7.32-7.38 (m, 10H, 2C6H5), 8.32-8.36 (m,
3H, 3NH). C20H18N4O3S (394.46): Calcd: C, 60.90; H,
4.60; N, 14.20; S, 8.13%. Found: C, 61.21; H, 4.75; N,
14.50; S, 8.45%.
ACKNOWLEDGEMENT
R. M. Mohareb expresses his deepest thanks to the
Alexander von Humboldt Foundation for financing him
during his stay in Germany Stuttgart University during
summer 2004 and 2006 and completing this work.
4-Amino-5-benzoyl-3-N-benzoylhydrazido-2-phenyl-
aminothiophene (35)
Brick yellow crystals from ethanol, yield 73.22%,
0.82 g, m.p. 80 ºC. IR (KBr): u/cm-1 = 3489-3323 (NH2, 3
NH), 3063 (CH aromatic), 1696, 1688-1680 (3C=O), 1643
(C=C). 1H NMR (DMSO) d = 4.57 (s, 2H, NH2), 7.22-7.35
(m, 15H, 3C6H5), 8.20, 9.23, 9.40 (3s, 3H, 3NH).
C25H20N4O3S (456.53): Calcd: C, 65.78; H, 4.42; N, 12.27;
S, 7.02%. Found: C, 65.99; H, 4.74; N, 12.59; S, 7.35%.
Received October 6, 2006.
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Synthesis of 7a,b and 38a,b
(General Procedure): To a solution of 3 (0.37 g, 1.82
´ 10-3 mol) in ethanol, an equimolar amount of either a-
cyanocinnamonitrile (36a), ethyl a-cyanocinnamate (36b),
4-methoxy-a-cyanocinnamonitrile (36c) or ethyl 4-meth-
oxy-a-cyanocinnamate (36d) is added and the resultant so-
lution is heated under reflux for 2 h. The contents are then
poured on an ice-water mixture and the precipitate is col-
lected by filtration.
3. Mohareb, R. M.; Al-Omran, F. A.; Ho, J. Z. Monatsh. Chem.
2002, 133, 1443.
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Yellow crystals from ethanol, yield 35.09%, 0.2 g,
m.p. 115 ºC. IR (KBr): u/cm-1 = 3460-3325 (NH2, 2NH),
3055 (CH aromatic), 2225, 2220 (2CN), 1688, 1683 (2CO),
1638 (C=C). 1H NMR (DMSO) d = 3.22 (s, 3H, CH3), 5.65
(s, 2H, NH2), 7.24-7.36 (m, 9H, C6H5, C6H4), 8.34 (s, 1H,
NH). C21H15N5O3 (385.39): Calcd: C, 65.45; H, 3.92; N,
18.17%. Found: C, 65.98; H, 4.30; N, 18.50%.
10. Boyd, R. E.; Press, J. B.; Rasmussen, C. R.; Raffa, R. B;
Codd, E. E.; Connelly, C. D.; Li, Q. S.; Martinez, R. P.;
Lewis, M. A.; Almond, B. J. J. Med. Chem. 2001, 44, 863.
11. Hadi, A.; Martin, N.; Seoane, C.; Soto, J. L. J. Heterocycl.
Chem. 1992, 29, 1229.
12. Doss, S. H.; Wardakhan, W. W.; Louca, N. A. Arch. Pharm.
Res. 2001, 24, 377.
Ethyl 2-amino-1-benzoamino-5-cyano-4-(4-methoxy-
phenyl)-6-oxo-pyridine-3-carboxylate (38b)
13. Mohareb, R. M.; Shams, H. Z.; Aziz, S. I. J. Chem. Res.
1992, (S) 154 (M), 1132.
Yellowish white crystals from ethanol, yield 46.88%,
0.3 g, m.p. 55 ºC. IR (KBr): u/cm-1 = 3468-3312 (NH2, H),
3050 (CH aromatic), 2988, 2890 (CH3, CH2), 2222, 2220
(2CN), 1692, 1686 (2CO), 1636 (C=C). 1H NMR (DMSO)
d = 1.16 (t, 3H, CH3), 3.22 (s, 3H, CH3), 4.26 (q, 2H, CH2),
5.62 (s, 2H, NH2), 7.26-7.34 (m, 9H, C6H5, C6H4), 8.30 (s,
1H, NH). C23H20N4O5 (432.44): Calcd: C, 63.88; H, 4.66;
N, 12.96%. Found: C, 64.31; H, 5.01; N, 13.35%.
14. Mohareb, R. M.; Shams, H. Z.; El-Kholy, Y. M. Phosphorus,
Sulfur Silicon Relat. Elem. 1992, 70, 317.
15. Mohareb, R. M.; Sherif, S. M. Sulfur Lett. 1992, 15(1), 91.
16. Mohareb, R. M.; El-Kousy, S.; El-Torgoman, A. M. Collect.
Czech. Chem. Commun. 1992, 57, 1747.
17. Mohareb, R. M.; Aziz, S. I.; El-Sayed, N. I.; Shams, H. Z.
Chin. Chem. Soc. 1992, 39, 181.
18. El-Kousy, S. M.; Mohareb, R. M.; Sherif, S. M. J. Chem.
Res. 1993, (S) 312, (M), 1981.