Pyrazole and Nicotinonitrile Derivatives Synthesized from Sulfa Drugs, and Their Antibacterial Activity

Article abstract of DOI:10.1134/S1070363219020270

Utility of sulfadiazine and sulfaguanidine in synthesis of new series of pyrazoles and 2-pyridones is described. Diazotization of sulfadiazine that results in formation of diazonium salt 2 followed by coupling of the latter with active methylene compounds

Full text of DOI:10.1134/S1070363219020270

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 2, pp. 339–347. © Pleiades Publishing, Ltd., 2019.
Pyrazole and Nicotinonitrile Derivatives Synthesized
from Sulfa Drugs, and Their Antibacterial Activity
H. A. El-Sayeda*, A. H. Moustafaa**, A. A. Faddab, and K. E. Abd El-Rahmana
a Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519 Egypt
b Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt
e-mail: *hasanneg@gmail.com; **ah_hu_mostafa@yahoo.com
Received November 30, 2018; revised January 26, 2019; accepted February 3, 2019
Abstract―Utility of sulfadiazine and sulfaguanidine in synthesis of new series of pyrazoles and 2-pyridones is
described. Diazotization of sulfadiazine that results in formation of diazonium salt 2 followed by coupling of
the latter with active methylene compounds leads to hydrazinyl derivatives 3a–3d. Heterocyclization of
compounds 3a–3c with hydrazine derivatives gives to a series of pyrazole derivatives 4–6. Similarly, a series of
pyrazole derivatives 12–14 is developed from sulfaguanidine. Condensation of hydrazinyl derivatives 3a–3c
with cyanoacetamide in the presence of a catalytic amount of piperidine gives 2-oxonicotinonitriles 15a–15c.
Tests of the new synthesized compounds against four pathogenic gram (+ve) and gram (–ve) bacteria
demonstrate their activity higher than that of the standard Amoxicillin.
Keywords: sulfa-drugs, pyrazole derivatives, 2-pyridone derivatives, diazonium salts, antimicrobial activity
DOI: 10.1134/S1070363219020270
INTRODUCTION
oxo-N'-{4-[N-(pyrimidin-2-yl)sulfamoyl]phenyl}aceto-
hydrazonoyl cyanide (3d) the bands recorded at 3424,
3150, 2209, and 1675 cm–1 were attributed to NH2,
Most of synthetic sulfonamides are known as anti-
inflammatory [1], anti-α-glucosidase [2], antimicrobial
[3, 4], antimalarial [5], and antitumor [6] agents.
Majority of 2-oxonicotinonitriles (2-ONN) containing
compounds are reported as anticancer [7], antimicro-
bial [7–9], antiviral agents [10], and enzymes inhi-
bitors [11]. Our recent studies were directed towards
the development of new heterocylic systems of
biological interest [4, 7–11]. Herein, we present the
use of the compounds known as sulfa-drugs in the syn-
thesis of new series of pyrazole and pyridine derivatives.
1
NH, C≡N, and C=O, accordingly. In the H NMR
spectrum of the product 3d three singlets and the
multiplet at 6.90, 11.54, 12.98, and 7.0–8.48 ppm cor-
responded to NH2, 2NH, and aromatic protons
indicating formation of the target compound, which
was also supported by its 13C NMR spectrum.
1,3-Bielectrophilic centers of compounds 3a–3d
enabled these to be used as reactive intermediates in
synthesis of polyfunctional heterocyclic ring systems.
Application of hydrazone derivatives 3a–3c as build-
ing blocks in formation of biologically active pyrazole
candidates is depicted in Scheme 2. Refluxing of com-
pounds 3a–3c with hydrazine hydrate, phenylhyd-
razine or 2,4-dinitrophenylhydrazine in ethanol led to
the target pyrazole derivatives 4–6, respectively, with
high yields (80–85%). Structures of the compounds
4–6 were elucidated from the spectral data. For
instance, IR spectrum of 4-{2-[3-amino-5-oxo-1H-
pyrazol-4(5H)-ylidene]hydrazinyl}-N-(pyrimidin-2-yl)-
benzenesulfonamide (4a) contained three main bands
at 3400, 3192, and 1640 cm–1 attributed to NH2, NH
and C=O groups, respectively. Formation of the
products was supported also by 1H and 13C NMR spectra.
RESULTS AND DISCUSSION
Initially, free primary amino function of sulfadi-
azine 1 was converted to the desired aryl diazonium
chloride 2 via diazotization with sodium nitrite and
hydrochloric acid at low temperature. The intermediate
2 reacted with an α-CH acid (ethyl cyanoacetate, acetyl
acetone, ethyl acetoacetate, or cyanoacetamide) under
milde conditions giving the corresponding target
hydrazinyl derivatives 3a–3d (Scheme 1). Structures
of molecules of 3a–3d were confirmed by the spectral
data, for example, in the IR spectrum of 2-amino-2-
339

340
EL-SAYED et al.
Scheme 1. Reaction of dizonium salt 2 with α-CH acids.
Cl
+
N
N
NH2
H O
H O
N
N
N
N
NaNO2, HCl
S
S
N
O
AcOH, 0−5oC
N
O
1
2
O
CH3CO2Na
EtOH, H2O
Y
0oC−room temperature
X
X
H
N
Y
N
H O
N
N
O
S
N
O
3a−3d
X = CN, Y = OEt (a); Ac, Y = CH3 (b); Ac, Y = OEt (c); CN, Y = NH2 (d).
The compounds 4 and 6 can exist in the form of
three possible tautomeric structures (hydrazo-keto form
1, azo-keto form 2 and azo-enol form 3) (see the
figure). Presence of the most favorable hydrazo-keto
form 1 was indicated by IR and NMR spectra. The IR
spectrum demonstrated the intense absorption bands
typical for pyrazolone-carbonyl groups in the range of
1640 to 1693 cm–1. The presence of low field signals
of NH protons and the absence of pyrazole-H4 and
1
pyrazole-C4 (aliphatic region) signals in H and 13C
NMR spectra was the clear evidence for the formation
of compounds 4 and 6 in the hydrazo-keto form 1.
Scheme 2. Synthetic route of pyrazole derivatives 4–6.
H3C
N
H2N
N
N
H
N R
N R
N
N
N
H O
N
H O
CH3
O
N
N
N
S
S
N
O
N
O
5a−5c
4a−4c
R
H
N
x
u
H
E
NH2NHR
EtOH, reflux
N
l
f
,
e
b
r
3a
3
,
H
O
t
H3C
N
N
X
H
H
N
N
N R
N
Y
3c, NH2NHR
H O
H O
N
EtOH, reflux
O
N
N
N
O
S
S
N
O
N
O
6a−6c
3a−3c
X = CN, Y = OEt (3a), X= Ac, Y = CH3 (3b), X= Ac, Y = OEt (3c); R = H (4a–6a), C6H5 (4b–6b), 2,4-(NO2)2C6H4 (4c–6c).
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PYRAZOLE AND NICOTINONITRILE DERIVATIVES SYNTHESIZED FROM SULFA DRUGS
341
absent in 1H NMR
present at low field
in 13C NMR
R'
present in 1H NMR
N
H
R'
N R
N
N
H
N
N
N R
H O
N
C
O
N
N
S
H O
2
O
N
N
Azo-keto
N
O
S
1
ν =1640−1693 cm−1
N
O
R'
N
Hydrazo-keto
N R
N
N
H O
OH
`
N
N
S
3
N
O
absent in IR and
1H NMR
Azo-enol
Three possible tautomeric forms of pyrazolones 4 and 6.
Sulfaguanidine was also subjected to diazotization
followed by coupling with an α-CH acid (ethyl
cyanoacetate, acetyl acetone or ethyl acetoacetate) in
the presence of sodium acetate affording hydrazinyl
derivatives 9–11. Heterocyclization of the latter
compounds with hydrazine hydrate, phenyl hydrazine
or 2,4-dinitrophenyl hydrazine gave the desired
pyrazole derivatives 12–14 (Scheme 3). Structures of
the products 9–14 were confirmed by the correspond-
ing spectral data.
by the microbial suspension and pouring in sterile
plates, the cultures were incubated overnight for pre-
germination, and then 300 µg of each tested compound
was pipetted to the wells of the plate cultures. The
cultures were incubated for 2 days at 37ºC for bacterial
growth. The antimicrobial activity was expressed by
the diameter of inhibitory zone compared with that of
amoxycillin used as the standard.
According to the accumulated data (see the table),
the compounds 3c, 3d, 4a–4c, 5a, 5c, 6a–6c, 10, and
14a, 14b demonstrated high antibacterial activity.
Finally, compounds 3a–3c were used as reactive
synthons in the synthesis of 2-oxonicotinonitrile
derivatives 15a-c (Scheme 4). The cyano and lactam
groups of 2-oxonicotinonitriles were recorded in IR
spectra by the bands at 2357, 2222, 2214, and 3438,
EXPERIMENTAL
Melting points were determined on an Electro
thermal IA 9100 apparatus and are uncorrected. IR
spectra were recorded in KBr on a Pye Unicam Sp-3–
1
3434, 3421, 1696, 1691, 1645 cm–1, respectively. H
NMR spectra confirmed formation of pyridone, signals
of the lactam protons were measured at 12.31, 12.01,
and 11.74 ppm. Also, the NH2 group protons of
compound 15a were measured at 4.47 ppm as a
singlet, and 2CH3 protons of compound 15b were
recorded as a singlet at 2.41 ppm.
1
300 infrared spectrophotometer. H and 13C NMR
spectra were measured at Cairo University, Cairo,
Egypt, on a Bruker Avance 400 spectrometer using
DMSO-d6 as a solvent and TMS as a standard.
Elemental analyses were carried out on a Perkin Elmer
240 at Microanalysis Center, Cairo University, Cairo,
Egypt. MS were measured on a Shimadzu GCMS-QP
1000 EX mass spectrometer.
Antibacterial activity. Antibacterial activity of
some synthesized compounds was tested against Gram
+ve Staphylococcus aureus and Bacillus cereus, and
Gram –ve Pseudomonas aeruginosa and Acineto-
bacteria, in Microbiology Department, Faculty of
Science, Zagazig Univesity using well diffusion
method [12]. After seeding the cooled-solid medium
Synthesis of hydrazo compounds 3a–3d. To a
mixture of sulfadiazine (0.01 mol) with acetic acid
(15 mL), conc. HCl (5 mL) and water (5 mL), a
solution of sodium nitrite (0.02 mol in 10 mL H2O)
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EL-SAYED et al.
Scheme 3. Utility of sulfaguanidine in pyrazole synthesis.
Cl
N
N
NH2
O
O
S
H2N
N
H2N
N
NaNO2, HCl
S
AcOH, 0−5oC
NH2
O
NH2
O
7
8
O
CH3CO2Na
EtOH, H2O
0oC−room temperature
Y
X
X
H2N
N
H
N
N
N
Y
N
H
O
S
R
NH2NHR, 9
EtOH, reflux
N
H2N
N
O
O
S
O
H2N
N
NH2
O
NH2
O
9−11
12a−12c
NH2NHR, 12
H3C
EtOH, reflux
N
N
R
N
N
H3C
O
S
N
CH3
H2N
N
H
N
R
N
NH2
O
N
13a, 13b
O
S
O
H2N
N
NH2
O
14a, 14b
X = CN, Y = OEt (9), X = Ac, Y = CH3 (10), X = Ac, Y = OEt (11); R = H (a), C6H5 (b), 2,4-(NO2)2C6H4 (c).
Scheme 4. Ring closure of compound 3a–3c to nicotinonitriles 15a–15c.
CN
R
O
X
H
N
NH
CN
O
N
Y
Pip. EtOH
reflux
N
N
+
H
N
O
S
O
S
N
R'
N
N
O
H2N
N
O
N
O
3a−3c
15a−15c
X = CN, Y = OEt (3a), X = Ac, Y = CH3 (3b), X = Ac, Y = OEt (3c); R = NH2, R' = OH (15a), R = R' = CH3 (15b), R =
CH3, R' = OH (15c).
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PYRAZOLE AND NICOTINONITRILE DERIVATIVES SYNTHESIZED FROM SULFA DRUGS
343
Antibacterial activities of some new synthesized compounds
Inhibition zone, mm
Compound
gram (+ve) bacteria
gram (–ve) bacteria
Staphylococcus aureus
Bacillus cereus
Pseudomonas aeruginosa
Acinetobacter
3c
18
20
21
20
23
16
20
23
21
22
16
17
18
20
–
16
18
19
23
20
17
19
15
20
21
20
16
17
19
–
12
16
18
20
22
18
17
18
19
16
15
19
14
16
–
13
15
18
12
13
15
22
16
13
14
10
15
13
15
–
3d
4a
4b
4c
5a
5c
6a
6b
6c
10
14a
14b
Amoxycillin
DMF
1
was added portion-wise at 0–5°C. Thus formed
diazonium salt 2 was added to a solution of an active
methylene compound (ethyl cyanoacetate, acetyl
acetone, ethyl acetoacetate, or cyanoacetamide)
(0.01 mol) and sodium acetate (0.01 mol) in 25 mL
ethanol and 5 mL water at 0–5°C. After stirring for 2 h,
the solid precipitate was filtered off, dried and crystal-
lized from the appropriate solvent, as indicated below.
spectrum, ν, cm–1: 3439 (NH), 1673 (C=O). H NMR
spectrum, δ, ppm: 2.42 s (3H, Hmethyl), 2.49 s (3H,
3
H
methyl), 7.04 t (1H, J = 4.80 Hz, Hpym), 7.70 d (2H,
3J = 8.70 Hz, HPh), 8.00 d (2H, 3J = 8.70 Hz, HPh), 8.50
d (2H, 3J = 4.80 Hz, Hpym), 11.78 s, 13.50 s (2H, 2NH).
Found, %: C 49.94; H 4.14; N 19.31. C15H15N5O4S.
Calculated, %: C 49.85; H 4.18; N 19.38.
Ethyl 3-oxo-2-(2-{4-[N-(pyrimidin-2-yl)sulfamoyl]-
phenyl}hydrazono)butanoate (3c). Yellow crystals
(EtOH), yield 88 %, mp 144–146°C. IR spectrum, ν,
Ethyl 2-cyano-2-(2-{4-[N-(pyrimidin-2-yl)sulfa-
moyl]phenyl}hydrazono)acetate (3a). Yellow crystals
(EtOH), yield 85.4%, mp 220–221°C. IR spectrum, ν,
cm–1: 3238 (NH), 3100 (NH), 2217 (C≡N), 1722
1
cm–1: 3414 (NH), 1698 (C=O), 1642 (C=O). H NMR
spectrum, δ, ppm: 1.26 t (3H, 3J = 6.80 Hz, Hethyl), 2.40
1
3
3
(C=O). H NMR spectrum, δ, ppm: 1.29 t (3H, J =
s (3H, Hmethyl), 4.30 q (2H, J = 6.80 Hz, Hethyl), 7.0 t
7.20 Hz, Hethyl), 4.31 q (2H, 3J = 7.20 Hz, Hethyl), 7.03 t
(1H, J = 5.10 Hz, Hpym), 7.60 d (2H, J = 8.70 Hz,
HPh), 7.98 d (2H, J = 8.70 Hz, HPh), 8.49 d (2H, J =
5.10 Hz, Hpym), 11.79 s, 12.40 s (2H, 2NH). Found, %:
C 48.01; H 3.72; N 22.54. C15H14N6O4S. Calculated,
%: C 48.12; H 3.77; N 22.45.
(1H, 3J = 4.0 Hz, Hpym), 7.51 d (2H, 3J = 8.40 Hz, HPh),
7.94 d (2H, 3J = 8.40 Hz, HPh), 8.47 d (2H, 3J = 4.0 Hz,
3
3
3
3
Hpym), 11.54 s, 13.78 s (2H, 2NH). Found, %: C 49.18;
H 4.32; N 17.96. C16H17N5O5S. Calculated, %: C
49.10; H 4.38; N 17.89.
2-Amino-2-oxo-N'-{4-[N-(pyrimidin-2-yl)sulfa-
moyl]phenyl}acetohydrazonoyl cyanide (3d). Buff
crystals (EtOH), yield 82%, mp 145–147°C. IR
spectrum, ν, cm–1: 3424 (NH), 3150 (NH2), 2209
4-{2-[2,4-Dioxopentan-3-ylidene]hydrazinyl}-N-
(pyrimidin-2-yl)benzenesulfonamide (3b). Yellow
crystals (EtOH), yield 90%, mp 110–112°C. IR
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EL-SAYED et al.
(C≡N), 1675 (C=O). 1H NMR spectrum, δ, ppm: 6.90 s
(2H, NH2), 7.0–8.48 m (7H, Hpym, Ph), 11.54 s, 12.98 s
(2H, 2NH). 13C NMR spectrum, δ, ppm: 25.7, 116.3,
123.3, 127.8, 129.2, 133.1, 141.3, 153.7, 158.7, 164.5,
172.5. Found, %: C 45.33; H 3.17; N 28.45. C13H11N7O3S.
Calculated, %: C 45.21; H 3.21; N 28.39.
crystals (MeOH), yield 67% mp 258–260°C. IR
1
spectrum, ν, cm–1: 3225 and 3123 (2NH). H NMR
spectrum, δ, ppm: 2.45 s (6H, Hmethyl), 7.05 t (1H, 3J =
3
4.80 Hz, Hpym), 7.82 d (2H, J = 8.40 Hz, HPh), 8.08 d
3
3
(2H, J = 8.40 Hz, HPh), 8.50 d (2H, J = 4.80 Hz,
H
pym), 12.22 s, 12.70 s (2H, 2NH). 13C NMR spectrum,
δ, ppm: 10.90, 14.00, 115.7, 121.7, 124.5, 128.2, 128.9,
129.3, 135.9, 138.4, 140.6, 141.2, 142.4, 155.0, 156.8,
158.3. Found, %: C 50.50; H 4.19; N 27.36. C15H15N7O2S.
Calculated, %: C 50.41; H 4.23; N 27.43.
Synthesis of pyrazole derivatives 4–6. A mixture
of one of compounds 3a–3c (0.01 mol) with hydrazine,
phenyl
hydrazine
or
dinitrophenylhydrazine
(0.01 mol) in ethanol (25 mL) was refluxed for 4–6 h
(monitored by TLC). After completion of the reaction
and cooling the mixture down, the precipitate was
filtered off, dried and crystallized from an appropriate
solvent.
4-[(3,5-Dimethyl-1-phenyl-1H-pyrazol-4-yl)dia-
zenyl]-N-(pyrimidin-2-yl)benzenesulfonamide (5b).
Orange crystals (EtOH), yield 64%, mp 236–240°C.
1
IR spectrum, ν, cm–1: 3435 (NH). H NMR spectrum,
δ, ppm: 2.47 s, 2.65 s (6H, Hmethyl), 7.04–8.52 m (12H,
H
4-{2-[3-Amino-5-oxo-1H-pyrazol-4(5H)-ylidene]
hydrazinyl}-N-(pyrimidin-2-yl)benzenesulfonamide
(4a). Brown crystals (MeOH), yield 50%, mp 280–
282°C. IR spectrum, ν, cm–1: 3400 (NH), 3192 (NH2),
pym, aryl), 11.97 s (1H, NH). 13C NMR spectrum, δ,
ppm: 10.96, 14.05, 115.7, 121.7, 124.5, 128.2, 128.9,
129.3, 135.9, 138.0, 138.4, 140.6, 141.2, 142.4, 148.3,
155.0, 156.8, 158.3. Found, %: C 58.08; H 4.39; N
22.67. C21H19N7O2S. Calculated, %: C 58.19; H 4.42;
N 22.62.
1
1640 (C=O). H NMR spectrum, δ, ppm: 5.95 s (2H,
NH2), 7.04 t (1H, 3J = 4.80 Hz, Hpym), 7.66 d (2H, 3J =
3
8.80 Hz, HPh), 7.93 d (2H, J = 8.80 Hz, HPh), 8.50 d
(2H, 3J = 4.80 Hz, Hpym), 10.61 s, 11.64 s, 12.87 s (3H,
3NH). 13C NMR spectrum, δ, ppm: 48.57, 114.6, 115.7,
125.9, 129.2, 134.5, 145.6, 149.7, 156.8, 158.0, 158.3.
Found, %: C 43.44; H 3.33; N 31.17. C13H12N8O3S.
Calculated, %: C 43.33; H 3.36; N 31.10.
4-{[1-(2,4-Dinitrophenyl)-3,5-dimethyl-1H-pyrazol-
4-yl]diazenyl}-N-(pyrimidin-2-yl)benzenesulfonamide
(5c). Yellow crystals (EtOH), yield 70%, mp 164–166°C.
1
IR spectrum, ν, cm–1: 3181 (NH). H NMR spectrum,
δ, ppm: 2.42 s, 2.46 s (6H, Hmethyl), 7.03–8.85 m (10H,
H
pym, aryl), 11.78 s (1H, NH). Found, %: C 48.30; H
4-{2-[3-Amino-5-oxo-1-phenyl-1H-pyrazol-4(5H)-
ylidene]hydrazinyl}-N-(pyrimidin-2-yl)benzene-
sulfonamide (4b). Yellow crystals (EtOH), yield 56%,
mp 230–232°C. IR spectrum, ν, cm–1: 3417 (NH),
3.23; N 24.15. C21H17N9O6S. Calculated, %: C 48.18;
H 3.27; N 24.08.
4-{2-[3-Methyl-5-oxo-1H-pyrazol-4(5H)-ylidene]-
hydrazinyl}-N-(pyrimidin-2-yl)benzenesulfonamide
(6a). Orange crystals (EtOH), yield 70%, mp 256–
258°C. IR spectrum, ν, cm–1: 3431 (NH), 1667 (C=O).
1H NMR spectrum, δ, ppm: 2.14 s (3H, Hmethyl), 6.97 t
1
3164 (NH2), 1693 (C=O). H NMR spectrum, δ, ppm:
4.33 s (2H, NH2), 7.04–8.50 m (12H, Hpym, aryl), 11.81,
12.93 (2s, 2H, 2NH). 13C NMR spectrum, δ, ppm:
61.70, 106.2, 106.8, 115.4, 115.9, 129.3, 129.4, 135.4,
136.2, 144.5, 145.4, 156.8, 158.3, 159.9, 160.4. Found,
%: C 52.19; H 3.67; N 25.71. C19H16N8O3S.
Calculated, %: C 52.29; H 3.70; N 25.67.
3
3
(1H, J = 4.40 Hz, Hpym), 7.62 d (2H, J = 8.40 Hz,
3
3
HPh), 7.96 d (2H, J = 8.40 Hz, HPh), 8.45 d (2H, J =
4.40 Hz, Hpym), 9.60 s, 11.62 s, 13.0 s (3H, 3NH).
Found, %: C 46.88; H 3.69; N 27.36. C14H13N7O3S.
Calculated, %: C 46.79; H 3.65; N 27.28.
4-{2-[3-Amino-1-(2,4-dinitrophenyl)-5-oxo-1H-
pyrazol-4(5H)-ylidene]hydrazinyl}-N-(pyrimidin-2-
yl)benzenesulfonamide (4c). Yellow crystals (AcOH),
yield 48%, mp 185–187°C. IR spectrum, ν, cm–1: 3339
(NH), 3182 (NH2), 1659 (C=O). 1H NMR spectrum, δ,
ppm: 7.03–8.50 m (10H, Hpym, aryl), 8.85 s (2H, NH2),
11.77 s, 12.41 s (2H, 2NH). Found, %: C 43.23; H
2.71; N 26.66. C19H14N10O7S. Calculated, %: C 43.35;
H 2.68; N 26.61.
4-{2-[3-Methyl-5-oxo-1-phenyl-1H-pyrazol-4(5H)-
ylidene]hydrazinyl}-N-(pyrimidin-2-yl)benzene-
sulfonamide (6b). Orange crystals (EtOH), yield 56%,
mp 220–222°C. IR spectrum, ν, cm–1: 3431 (NH),
1
1646 (C=O). H NMR spectrum, δ, ppm: 2.30 s (3H,
Hmethyl), 6.67–8.52 m (12H, Hpym, aryl), 11.81 s, 13.19 s
(2H, 2NH). Found, %: C 55.05; H 3.88; N 22.60.
C20H17N7O3S. Calculated, %: C 55.16; H 3.93; N
22.52.
4-[(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl]-N-
(pyrimidin-2-yl)benzenesulfonamide (5a). Yellow
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4-{2-[1-(2,4-Dinitrophenyl)-3-methyl-5-oxo-1H-
pyrazol-4(5H)-ylidene]hydrazinyl}-N-(pyrimidin-2-
yl)benzenesulfonamide (6c). Brown crystals (EtOH),
yield 65%, mp 270–272°C. IR spectrum, ν, cm–1: 3435
4-{2-[3-Amino-5-oxo-1H-pyrazol-4(5H)-ylidene]-
hydrazinyl}-N-(diaminomethylene)benzenesulfonamide
(12a). Yellow crystals (EtOH), yield 74%, mp 210–
212°C. IR spectrum, ν, cm–1: 3445 (NH), 3346 (NH2),
1
1
(NH), 1679 (C=O). H NMR spectrum, δ, ppm: 2.32 s
1699 (C=O). H NMR spectrum, δ, ppm: 6.69 m (6H,
(3H, Hmethyl), 7.05–8.76 m (10H, Hpym, aryl), 11.86 s,
12.88 s (2H, 2NH). Found, %: C 45.81; H 2.85; N
24.05. C20H15N9O7S. Calculated, %: C 45.72; H 2.88;
N 23.99.
3NH2), 7.50 d (2H, 3J = 8.40 Hz, HPh), 7.60 d (2H, 3J =
8.40 Hz, HPh), 12.38 s, 12.96 s (2H, 2NH). 13C NMR
spectrum, δ, ppm: 54.20, 105.0, 115.9, 140.2, 144.6,
158.0, 160.8, 172.0. Found, %: C 37.11; H 3.70; N
34.61. C10H12N8O3S. Calculated, %: C 37.03; H 3.73;
N 34.55.
Synthesis of hydrazo compounds 9–11. Com-
pounds 9–11 were synthesized according to the
method similar to that of compounds 3a–3d using
sulfaguanidine instead of sulfadiazine.
4-{2-[3-Amino-5-oxo-1-phenyl-1H-pyrazol-4(5H)-
ylidene]hydrazinyl}-N-(diaminomethylene)benzene-
sulfonamide (12b). Yellow crystals (EtOH), yield
76.5%, mp 218–220°C. IR spectrum, ν, cm–1: 3434
(NH), 3342 (NH2), 1696 (C=O). 1H NMR spectrum, δ,
ppm: 6.69 m (6H, 3NH2), 7.54–7.77 m (9H, Haryl),
12.95, s (1H, NH). 13C NMR spectrum, δ, ppm: 105.4,
106.0, 111.2, 112.1, 115.8, 116.0, 127.2, 140.3, 144.0,
158.0, 160.2, 160.6. Found, %: C 48.07; H 4.01; N
27.93. C16H16N8O3S. Calculated, %: C 47.99; H 4.03;
N 27.98.
Ethyl 2-cyano-2-{2-[4-(N-[diaminomethylene]-
sulfamoyl)phenyl]hydrazono}acetate (9). Yellow
crystals (EtOH), yield 90%, mp 223–225°C. IR
spectrum, ν, cm–1: 3446 (NH), 3343 (NH2), 2225
(C≡N), 1717 (C=O). 1H NMR spectrum, δ, ppm: 1.29 t
3
3
(3H, J = 7.20 Hz, Hethyl), 4.30 q (2H, J = 7.20 Hz,
H
ethyl), 6.69 br.s (4H, 2NH2), 7.51 d (2H, 3J = 8.40 Hz,
HPh), 7.75 d (2H, 3J = 8.40 Hz, HPh), 12.37 s (1H, NH).
Found, %: C 42.49; H 4.22; N 24.91. C12H14N6O4S.
Calculated, %: C 42.60; H 4.17; N 24.84.
4-{2-[3-Amino-1-(2,4-dinitrophenyl)-5-oxo-1H-
pyrazol-4(5H)-ylidene]hydrazinyl}-N-(diaminome-
thylene)benzenesulfonamide (12c). Yellow crystals
(EtOH), yield 70.8%, mp 184–186°C. IR spectrum, ν,
N-(Diaminomethylene)-4-[2-(2,4-dioxopentan-3-
ylidene)hydrazinyl]benzenesulfonamide (10). Yellow
crystals (EtOH), yield 92%, mp 250–252°C. IR
spectrum, ν, cm–1: 3439 (NH), 3343 (NH2), 1681 and
1
cm–1: 3439 (NH), 3340 (NH2), 1655 (C=O). H NMR
spectrum, δ, ppm: 6.70 m (6H, 3NH2), 7.21 d (1H, 3J =
9.60 Hz, Haryl), 7.52 d (2H, 3J = 8.40 Hz, Haryl), 7.60 d
1
1623 (C=O). H NMR spectrum, δ, ppm: 2.43 s (6H,
H
methyl), 6.88 br.s (4H, 2NH2), 7.61 d (2H, 3J =
3
3
3
(2H, J = 8.40 Hz, Haryl), 8.29 d (1H, J = 9.60 Hz,
8.80 Hz, HPh), 7.74 d (2H, J = 8.80 Hz, HPh), 12.10 s
(1H, NH). 13C NMR spectrum, δ, ppm: 23.00, 116.0,
127.1, 134.9, 140.3, 144.9, 158.2, 196.6. Found, %: C
44.39; H 4.63; N 21.59. C12H15N5O4S. Calculated, %:
C 44.30; H 4.65; N 21.53.
H
aryl), 8.85 s (1H, Haryl), 10.40 s (1H, NH). 13C NMR
spectrum, δ, ppm: 105.4, 111.4, 115.4, 123.1, 127.2,
129.5, 130.0, 136.6, 140.3, 141.0, 143.1, 144.0, 148.5,
168.9. Found, %: C 39.28; H 2.91; N 28.50.
C16H14N10O7S. Calculated, %: C 39.19; H 2.88; N
28.56.
Ethyl 2-{2-[4-(N-[diaminomethylene]sulfamoyl)-
phenyl]hydrazono}-3-oxobutanoate (11). Yellow
crystals (EtOH), yield 88%, mp 178–180°C. IR
spectrum, ν, cm–1: 3438 (NH), 3229 (NH2), 1703 and
N-(Diaminomethylene)-4-[(3,5-dimethyl-1H-
pyrazol-4-yl)diazenyl]benzenesulfonamide (13a).
Orange crystals (EtOH), yield 70%, mp 216–218°C.
IR spectrum, ν, cm–1: 3426, 3326 and 3233 (2NH2 and
1
1633 (C=O). H NMR spectrum, δ, ppm: 1.27 t (3H,
3J = 7.20 Hz, Hethyl), 2.40 s (3H, Hmethyl), 4.30 q (2H,
3J = 7.20 Hz, Hethyl), 6.72 br.s (4H, 2NH2), 7.47 d (2H,
1
NH). H NMR spectrum, δ, ppm: 2.43 s (6H, Hmethyl),
3
3
3J = 8.40 Hz, HPh), 7.72 d (2H, J = 8.40 Hz, HPh),
6.77 br.s (4H, 2NH2), 7.78 d (2H, J = 8.44 Hz, Haryl),
7.87 d (2H, 3J = 8.44 Hz, Haryl), 12.94 s (1H, NH). 13C
NMR spectrum, δ, ppm: 19.02, 20.91, 121.9, 127.2,
135.0, 139.8, 143.3, 145.0, 154.8, 158.6. Found, %: C
44.74; H 4.68; N 30.45. C12H15N7O2S. Calculated, %:
C 44.85; H 4.70; N 30.51.
12.30 s (1H, NH). 13C NMR spectrum, δ, ppm: 13.86,
25.28, 61.28, 114.6, 127.2, 132.9, 138.9, 144.8, 158.0,
162.4, 162.7. Found, %: C 44.02; H 4.79; N 19.66.
C13H17N5O5S. Calculated, %: C 43.94; H 4.82; N 19.71.
Synthesis of pyrazole derivatives 12–14. Syn-
thesis of compounds 12–14 was similar to that of
compounds 4–6.
N-(Diaminomethylene)-4-[(3,5-dimethyl-1-phenyl-
1H-pyrazol-4-yl)diazenyl]benzenesulfonamide (13b).
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EL-SAYED et al.
Orange crystals (EtOH), yield 67.7%, mp 226–228°C.
IR spectrum, ν, cm–1: 3440 and 3188 (2NH2). 1H NMR
spectrum, δ, ppm: 2.40 s (3H, Hmethyl), 2.64 s (3H,
32.6, 99.17, 111.1, 115.6, 118.1, 121.2, 128.0, 129.0,
134.5, 143.3, 152.1, 157.8, 165.7, 173.2. Found, %: C
49.71; H 3.22; N 23.78. C17H13N7O4S. Calculated, %:
C 49.63; H 3.19; N 23.83.
H
methyl), 6.83 br.s (4H, 2NH2), 7.13–7.92 m (9H, Haryl).
13C NMR spectrum, δ, ppm: 21.07, 30.46, 112.5,
118.8, 122.1, 125.0, 127.3, 129.7, 136.2, 142.8, 145.4,
149.8, 145.6, 158.7. Found, %: C 54.48; H 4.79; N
24.72. C18H19N7O2S. Calculated, %: C 54.39; H 4.82;
N 24.67.
4-[(5-Cyano-2,4-dimethyl-6-oxo-1,6-dihydropyri-
din-3-yl)diazenyl]-N-(pyrimidin-2-yl)benzenesulfon-
amide (15b). Orange crystals (AcOH), mp 260–262°C,
yield 54.6%. IR spectrum, ν, cm–1: 3438 (NH), 2357
(C≡N), 1694 (C=O). 1H NMR spectrum, δ, ppm: 2.41 s
3
N-(Diaminomethylene)-4-{2-[3-methyl-5-oxo-1H-
pyrazol-4(5H)-ylidene]hydrazinyl}benzenesulfon-
amide (14a). Orange crystals (EtOH), yield 80%, mp
258–260°C. IR spectrum, ν, cm–1: 3442 (NH2), 3309
(6H, Hmethyl), 7.05 t (1H, J = 4.80 Hz, Hpym), 7.54 d
3
3
(2H, J = 8.76 Hz, Haryl), 7.96 d (2H, J = 8.76 Hz,
H
3
aryl), 8.50 d (2H, J = 4.80 Hz, Hpym), 11.58, 11.74 s
(2H, 2NH). 13C NMR spectrum, δ, ppm: 25.70, 30.90,
112.0, 115.0, 116.2, 128.6, 129.9, 134.4, 136.0, 145.9,
146.5, 157.4, 158.8, 162.6, 164.2. Found, %: C 52.71;
H 3.72; N 24.01. C18H15N7O3S. Calculated, %: C
52.80; H 3.69; N 23.95.
1
(NH), 1669 (C=O). H NMR spectrum, δ, ppm: 2.16 s
3
(3H, Hmethyl), 6.71 br.s (4H, 2NH2), 7.60 d (2H, J =
8.60 Hz, Haryl), 7.78 d (2H, 3J = 8.60 Hz, Haryl), 9.67 s,
11.61 s (2H, 2NH). 13C NMR spectrum, δ, ppm: 20.91,
115.8, 127.7, 129.9, 140.8, 144.1, 158.5, 160.4, 168.4.
Found, %: C 40.95; H 4.02; N 30.25. C11H13N7O3S.
Calculated, %: C 40.86; H 4.05; N 30.32.
4-[(4-Amino-5-cyano-2-hydroxy-6-oxo-1,6-dihyd-
ropyridin-3-yl)diazenyl]-N-(pyrimidin-2-yl)benzene-
sulfonamide (15a). Yellow crystals (AcOH), mp 280–
282°C, yield 60%. IR spectrum, ν, cm–1: 3421 (NH),
N-(Diaminomethylene)-4-{2-[3-methyl-5-oxo-1-
phenyl-1H-pyrazol-4(5H)-ylidene)-hydrazinyl)benzene-
sulfonamide (14b). Orange crystals (EtOH), yield
77%, mp 226–228°C. IR spectrum, ν, cm–1: 3437,
1
2222 (C≡N), 1691 (C=O). H NMR spectrum, δ, ppm:
4.42 br.s (2H, NH2), 6.83 t (1H, Hpym), 7.30 d (2H, 3J =
7.56 Hz, Haryl), 7.77 d (2H, 3J = 7.56 Hz, Haryl), 8.38 d
(2H, Hpym), 11.58, 12.01 (2s, 2H, 2NH). 13C NMR
spectrum, δ, ppm: 97.90, 114.1, 116.7, 118.8, 118.8,
128.7, 135.5, 157.8, 158.4, 159.8, 164.6, 166.0, 173.0.
Found: C 46.68; H 2.95; N 27.22. C16H12N8O4S.
Calculated, %: C 46.60; H 2.93; N 27.17.
1
3342, 3212 (NH2 and NH), 1707 (C=O). H NMR
spectrum, δ, ppm: 2.42 s (3H, Hmethyl), 6.70 br.s (4H,
2NH2), 7.21–7.92 m (9H, Haryl), 9.81 s (1H, NH). 13C
NMR spectrum, δ, ppm: 21.52, 116.4, 118.2, 125.3,
127.6, 129.5, 138.2, 141.4, 143.9, 149.1, 156.7, 158.5,
172.4. Found, %: C C 51.03; H 4.26; N 24.60.
C17H17N7O3S. Calculated, %: C 51.12; H 4.29; N
24.55.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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the reaction and cooling the mixture down, the
precipitate was filtered off, dried and crystallized from
an appropriate solvent.
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