Azopyrazolobenzylidene derivatives of 4-amino-1,2,4-triazol-3-ones. Synthesis of 4-{[4-(3,5-dimethyl-1H-pyrazol-4-yl)diazenyl]-benzylidene}amino-2- aryl-5-methyl-3H-[1,2,4]-triazol-3-ones

Article abstract of DOI:10.1002/jhet.5570440101

(Chemical Equation Presented) The Schiff bases 3a-h obtained from 4-amino-1,2,4-triazol-3-ones 1a-h when subjected to Japp-Klingemann reaction yielded the corresponding 3-{2-[(2-aryl-5-methyl-3H-[1,2,4]-triazol-3-one-4-yl)] -iminophenyl}-pentane-2,4-diones 4 a-h. These diones on cyclisation with N ₂H₄ yielded the title compounds 5a-h. The energetics of the Keto-enol tautomers of the diones was calculated by semiemperical calculations using AM1 and PM3 methods. All these compounds were screened for their antimicrobial activity against few microbes and most of them exhibited fungal inhibition more than the reference drugs used.

Full text of DOI:10.1002/jhet.5570440101

Jan-Feb 2007
1
Azopyrazolobenzylidene Derivatives of 4-Amino-1,2,4-triazol-3-ones.
Synthesis of 4-{[4-(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl]-
benzylidene}amino-2-aryl-5-methyl-3H-[1,2,4]-triazol-3-ones.
Vinay A. Sunagar, Prashant R. Latthe and Bharati V. Badami*
Postgraduate Department of Studies in Chemistry
Karnatak University, Dharwad-580 003, INDIA
bbadami@rediffmail.com
Received July 27, 2005
Revised May 25, 2006
H3C
C
O
R1
R2
O
R1
R2
4 steps
N
N
N
N
N
N
CH
N N
N
N NH2
NH
CH3
CH3
H3C
The Schiff bases 3a-h obtained from 4-amino-1,2,4-triazol-3-ones 1a-h when subjected to Japp-
Klingemann reaction yielded the corresponding 3-{2-[(2-aryl-5-methyl-3H-[1,2,4]-triazol-3-one-4-yl)]-
iminophenyl}-pentane-2,4-diones 4 a-h. These diones on cyclisation with N2H4 yielded the title compounds
5a-h. The energetics of the Keto-enol tautomers of the diones was calculated by semiemperical calculations
using AM1 and PM3 methods. All these compounds were screened for their antimicrobial activity against
few microbes and most of them exhibited fungal inhibition more than the reference drugs used.
J. Heterocyclic Chem., 44, 1 (2007).
INTRODUCTION
unreactive towards reagents like alpha-halogen esters,
KCNS, nitrous acid etc. indicating its weak nucleophilic
character, which is due to the strong electron-withdrawing
triazolinone ring. However, some Schiff bases of com-
pounds 1a-h have been prepared in our laboratory [2] by
reaction with aromatic aldehydes on prolonged heating.
One of these Schiff bases 2a-h (the p-nitro derivatives)
were found to be useful as they could be converted to
amino compounds 3a-h by reduction of the nitro group.
This amino group was reactive enough to undergo Japp-
Klingemann reaction resulting in the formation of the 2,4-
The facile synthesis of 4-amino-2-aryl-5-methyl-3H-
[1,2,4]-triazol-3-ones 1a-h from 3-arylsydnones by two
facile successive one-pot ring conversions has been
recently reported from our laboratory [1]. These new
triazolinone derivatives, reported for the first time, have
not been investigated for their reactions. Hence, we
thought of exploiting the synthetic utility of the potential
amino group in these compounds. In this paper we report
the synthetic utility of compounds 1a-h for the synthesis
of the title compounds 5a-h. The amino group was
Scheme
O
O
R1
R2
R1
R2
ꢀ
N
N
(i) p-nitrobenzaldehyde
(ii) Methanol
N
N
N
CH
NO2
N
N
NH2
(iii) Glacial acetic acid
CH3
CH3
2 a-h
(i) Sn / HCl
(ii) NaOH
ꢀ
1 a-h
O
O
R1
R2
H
N
C
CH3
CH3
O
N
R1
R2
0-5°C
(i) NaNO2 / HCl
N
N
N
C
H
N N C
N
N
N
CH
NH2
C
O
(ii) Acetylacetone / NaOAc
(iii) EtOH
4 a-h
CH3
3 a-h
ꢀ
N2H4 / EtOH
ꢀ
(CH3CO)2O
O
R1
R2
H3C
C
O
R1
R2
O
N
N
N
N
N
N
CH
NH
C CH3
N
N
N
CH
N
N
NH
CH3
CH3
H3C
5 a-h
6 a-h
(a) R1& R2=H; (b) R1=H& R2=4-Br; (c) R1=H & R2=3-Me; (d) R1=H & R2=4-Me; (e) R1=H & R2=3-Cl;
(f) R1=H & R2=4-Cl; (g) R1=H & R2=4-OCH3; (h) R1=3-Cl & R2=4-CH3;

2
V. A. Sunagar, P. R. Latthe and B. V. Badami
Vol 44
diones 4a-h. These diones were used as building blocks
for the preparation of the title compounds - 4-{[4-(3,5-
dimethyl-1H-pyrazol-4-yl)diazenyl]benzylidene}amino-2-
aryl-5-methyl-3H-[1,2,4]-triazol-3-ones 5a-h (Scheme).
The azopyrazoles are known to possess good biologi-
cal activity [3-6]. Heterocyclic azo dyes containing
pyrazole rings have also been used as pigments for dyeing
of paper and textiles and also as optical recording medium
for worm (write once read many) discs [7-8a]. Hence,
compounds 5a-h containing two heterocycles coupled
through the imine and the azo functions would be
expected to possess biological activity and would also be
suitable molecules for further structural modifications.
The experiments for exploring the application of these azo
compounds as dyes are under progress.
forms (stereochemistry of the imine group) by molecular
orbital methods - semiemperical calculations using AM1
and PM3 methods. We have evidenced the geometry of
the Schiff bases (imine double bond attached to the
triazolinone ring) by the X-ray crystal studies of a similar
type of the compound [9].
CH3
O
H
H
CH3
N
30
H
N
29
O
H
H
H
H
O
N
H
N
Cl
N
N
H
CH3
H
TA1
Spectral Characterisation. The IR spectra of the amino
compounds 3a-h showed bands for the asymmetric and
symmetric stretching vibrations of NH2 at 3401 cm-1 and
H
O
H
29
N
CH3
30
N
3326 cm-1 The ꢀC=O band of the triazolinone ring appeared
H
.
as a sharp band at 1703 cm-1. The 1H-NMR spectra of these
compounds showed a singlet at ꢁ 4.48 ppm (D2O
exchanged) for the NH2 protons. The singlets at ꢁ 2.48 ppm
(triazolinone CH3 protons) and ꢁ 9.70 ppm (the imine
proton) and the signals at ꢁ 7.43 - 7.94 ppm for the
aromatic protons did not show significant changes in the
rest of the compounds.
H
CH3
H
O
O
H
H
H
N
N
Cl
N
N
CH3
H
H
TA2
CH3
CH3
O
The IR spectra of the diones 4a-h showed a broad band
at 3438 cm-1 due to ꢀN-H vibrations. The ꢀC=O for the 2,4-
dione moiety appeared at 1678 cm-1, while the ꢀC=O of the
H
29
N
H
30
N
H
OH
1
triazolinone ring appeared at 1709 cm-1. The H-NMR
H
O
H
H
H
spectra of compounds 4a-h showed two singlets at ꢁ 2.42
and 2.44 ppm for the two –OCH3 groups of the 2,4-dione
and the imine –CH appeared at ꢁ 9.71ppm. The NH
proton observed at ꢁ 14.03 ppm was D2O exchanged.
The IR spectra of the pyrazole derivatives 5a-h showed
a broad band at 3215 cm-1 due to ꢀN-H vibrations and only
one ꢀC=O band of the triazolinone ring at 1709 cm-1. The
absence of the ꢀC=O at 1678 cm-1 evidences the formation
of the pyrazole ring.The 1H-NMR spectra of these
compounds showed the two –CH3 protons of the pyrazole
ring as two singlets at ꢁ 2.40 and 2.47 ppm. The spectrum
showed the presence of an -NH proton at ꢁ 12.90 ppm
(D2O exchanged).
N
Cl
N
N
N
H
CH3
H
TA3
O
H
29
N
CH3
N
H
H
30
CH3
H
O
H
HO
H
H
N
Cl
N
N
N
H
CH3
H
TA4
The N-acetyl derivatives 6a-h in their IR spectra showed
a band at 3320 cm-1 due to ꢀN-H vibrations. The ꢀC=O band of
1
the triazolinone ring appeared at 1709 cm-1 and the amide
1
ꢀ
C=O appeared at 1678 cm -1. The H-NMR spectra showed
the amide –CH3 protons at ꢁ 2.10 ppm while the amide –
NH resonated at ꢁ 10.03 ppm ( D2O exchanged).
Computational Details. The size of the system studied
prevents the use of ab initio molecular quantum
mechanical methods to perform optimization. Therefore,
full geometry optimization was carried out using the
MOPAC quantum chemical program [10]. The
calculations were carried out with the Restricted Hartree–
Fock formalization (RHF) using AM1 [11] and PM3 [12]
Semiemperical Calculations. The diones 4a-h would
possibly exist in keto-enol forms TA1 & TA3 and TA2 &
TA4 (N29-C30 –Syn form) (Figure 1). The spectral data
alone did not reveal which of the tautomeric or the
isomeric form is more preferred. Hence, we thought of
studying the energetics of these tautomeric and isomeric

Jan-Feb 2007
Azopyrazolobenzylidene Derivatives of 4-Amino-1,2,4-triazol-3-ones
3
semiemperical methods. All the calculations were carried
out using PC version of GAMESS.
RESULTS AND DISCUSSION
It can be inferred from the energy of heat of formation
(Table), that the keto form (TA1) in which the substituted
triazolinone ring and the 2,4-dione group are trans with
respect to NH-N- bond is more stable than the
corresponding cis isomer (TA2). Similarly, the enol form
(TA3) in which the substituted triazolinone ring and the
2,4-dione group are trans with respect to N=N bond is
more stable than the corresponding cis isomer (TA4). The
energy of heat of formation also indicates that the keto
form is more stable than the enol form.
TA4
Figure 2. The energy optimized structures.
Antimicrobial Activity. The preliminary antimicrobial
activity of all these compounds was assayed by using
cup-plate agar diffusion method, against two bacterial
strains- Bacillus cirroflagellosus (Gram-positive) and
Escherichia coli (Gram-negative) and Asperigillus niger
and Penicillium notatum as the fungal strains.
Norfloxacin and Griseofulvin were used as reference
drugs respectively. The compounds and the reference
drugs were screened under identical conditions at a dose
of 100 μg/1 ml with DMF as the control solvent. The
inhibition measured in mm is used only for qualitative
comparative studies. (Norfloxacin 15mm against E. coli
and 22 mm against B. cirroflagellosus and Griseofulvin
18 mm against P. notatum and 12 mm against A. niger).
All the halogenated compounds were found to be more
active against the fungi. Fungal inhibition was observed
for compounds 3a (20mm), 3d & 3f (both 21mm)
against P. notatum while all these, in particular the
halogenated derivatives, exhibited growth inhibition of
A. niger (14-16 mm), greater than Griseofulvin.
Compounds 5a, 5d, 5e and 5h were also selectively
active against P. notatum while the 4-chloro (5e)
exhibited inhibition only against A. niger (18mm),
considerably greater than Griseofulvin. Bacterial
inhibition against E.coli was exhibited by compounds
6d,6f & 6g (17mm) while only the chloro compounds
6e & 6f were active selectively against A. niger. It may
be noted here that all these microbial inhibitions are
found to be more than that of the reference drugs. This
observation initiated us to prepare some more
structurally modified compounds in the hope of
obtaining a potentially active drug and this work will be
submitted shortly.
Heat of formation (ꢀHf)
(Kcal/mol)
PM3
Structure
AM1
TA1
TA2
TA3
TA4
41.159
43.881
46.315
49.585
96.642
102.327
102.906
107.050
TA1
TA2
EXPERIMENTAL
The IR spectra were recorded on a NICOLET-IMPACT-410
1
FT-IR spectrophotometer. H-NMR spectra were recorded on a
Bruker AC-300 F, 300 MHz spectrometer in CDCl3/DMSO-d6
with TMS as internal standard. The mass spectra were recorded
on MIver 14 UIC 002002 spectrometer. Elemental analysis was
obtained on Heraus C, H, N rapid analyser.
TA3

4
V. A. Sunagar, P. R. Latthe and B. V. Badami
Vol 44
General Procedures. 4-[(4-Aminobenzylidene)-amino]-5-
(341.77): C, 59.73; H, 4.68; N, 20.48; Found: C, 59.34; H, 4.32;
N, 20.12.
methyl-2-aryl-2,4-dihydro-[1,2,4]-triazol-3-ones 3 a-h. To (0.5
g, 0.001 mol) of compound 2a-h and (0.250 g, 0.0015 mol) of
tin, 3 ml of concentrated hydrochloric acid was added drop-wise
and refluxed on a water bath till the solution was clear (30 min).
The reaction mixture was then cooled and made alkaline by
addition of NaOH solution and the amino derivatives were
extracted with THF. The amorphous pale yellow compounds
obtained after the evaporation of the solvent were purified by
crystallisation from ethanol.
General Procedure for Preparation of 3-{2-[(2-Aryl-5-
methyl-3H-[1,2,4]-triazol-3-one-4-yl)]-iminophenyl}-pentane-
2,4-diones (4 a-h). The amino compounds (3 a-h) (0.4 g, 0.001
mol) were diazotised in 0.4 ml HCl with a cold solution of
sodium nitrite (0.2 g, 0.001 mol in 2 ml of water) during a
period of 10 minutes. The reaction mixture was stirred for 30
minutes at 0-5°C. This diazotised solution was treated with
acetylacetone (0.001 mol) and sodium acetate (0.005 mol) in 10
ml of ethanol, during 15 minutes and stirred for one hour. The
reaction mixture was and stirred for one hour, then poured into
water and the solid obtained was collected by filtration and
crystallised from ethanol to get the 2,4-diones 4a: Yield 75%;
4-[(4-Aminobenzylidene)-amino]-5-methyl-2-phenyl-3H-
[1,2,4]-triazol-3-one (3a). Yield 73%; mp. 164-166 °C; ir 3326-
1
3401 (ꢀNH), 1709 (ꢀC=O); H-NMR: ꢁ 2.50(s, 3H, CH3), 4.45 (s,
2H, NH2), 7.20-7.95 (m, 8H, ArH), 9.55 (s, 1H, =CH). Mass
calcd for C16H15N5O: 293.15. Found: 293. Anal. Calcd. for
C16H15N5O(293.15): C, 65.55; H, 5.11; N, 23.87 %; Found: C,
65.12; H, 4.90; N, 23.51.
1
mp. 142-144°C; ir 3485 (ꢀNH), 1709 (ring ꢀC=O), 1675 (ꢀC=O); H-
NMR ꢁ 2.40-2.45(2s, 6H, (COCH3), 2.50(s, 3H, ring CH3), 7.40-
7.90(m, 8H, ArH), 9.71(s, 1H, =CH), 14.03(s, 1H, NH). Mass
calcd for C21H20N6O3: 404.18. Found: 404. Anal. Calcd. for
C21H20N6O3(404.18): C, 62.407; H, 4.94; N, 20.78; Found: C,
62.03; H, 4.68; N, 20.48.
4-[(4-Amino-benzylidene)-amino]-5-methyl-2-(4-bromo)-
phenyl-3H-[1,2,4]-triazol-3-one (3b). Yield 85%; mp.140-
1
142°C; ir 3320-3380 (ꢀNH), 1709 (ꢀC=O); H-NMR ꢁ 2.42(s, 3H,
CH3), 4.46(s, 2H, NH2), 7.30-7.86(m, 8H, ArH), 9.48(s, 1H,
=CH). Mass calcd for C16H14BrN5O: 372.22 & 374.22. Found:
372 & 374. Anal. Calcd. for C16H14BrN5O(372.22): C, 51.62; H,
3.76; N, 18.80; Found: C, 51.20; H, 3.28; N, 18.40.
3-{2-[(2-(4-Bromo)phenyl-5-methyl-3H-[1,2,4]-triazol-3-one-
4-yl)]-iminophenyl}-pentane-2,4-dione (4b). Yield 85%; mp.
135-137°C; ir 3438 (ꢀNH), 1709 (ring ꢀC=O), 1672 (ꢀC=O); 1H-NMR
ꢁ 2.42-2.44(2s, 6H, COCH3), 2.55(2s, 3H, ring CH3), 2.48(s, 3H,
ring CH3), 7.43-7.90(m, 8H, ArH), 9.75(s, 1H, =CH), 13.90(s, 1H,
NH). Mass calcd for C21H19BrN6O3: 483.32 & 485.32. Found:
483&485. Anal. Calcd. for C21H19BrN6O3 (483.32): C, 52.18; H,
3.93; N, 17.37;Found: C, 51.81; H, 5.60; N, 17.08.
3-{2-[(2-(3-Methyl)phenyl-5-methyl-3H-[1,2,4]-triazol-3-
one-4-yl)]-iminophenyl}-pentane-2,4-dione (4c). Yield 78%;
mp. 152-154°C; ir 3436 (ꢀNH), 1709 (ring ꢀC=O), 1676 (ꢀC=O); 1H-
NMR ꢁ 1.88 (s, 3H,CH3), 2.36-2.40(2s, 6H, COCH3), 2.45(2s,
3H, ring CH3), 7.40-7.90(m, 8H, ArH), 9.60(s, 1H, =CH),
13.90(s, 1H, NH). Mass calcd for C22H22N6O3: 418.81. Found:
418. Anal. Calcd. for C22H22N6O3(418.81): C, 63.08; H, 5.25; N,
20.05; Found: C, 62.85; H, 4.88; N, 19.78.
4-[(4-Amino-benzylidene)-amino]-5-methyl-2-(3-methyl)-
phenyl-3H-[1,2,4]-triazol-3-one (3c). Yield 78%; mp.160-
1
162°C; ir 3315-3368 (ꢀNH), 1709 (ꢀC=O); H-NMR ꢁ 1.87(s, 3H,
CH3), 2.45(s, 3H, CH3), 4.40(s, 2H, NH2), 7.20-7.95(m, 8H,
ArH), 9.45(s, 1H, =CH). Anal. Calcd. for C17H17N5O (307.31):
C, 66.43; H, 5.53; N, 22.77; Found: C, 66.01; H, 5.18; N, 22.48.
4-[(4-Amino-benzylidene)-amino]-5-methyl-2-(4-methyl)-
phenyl-3H-[1,2,4]-triazol-3-one (3d). Yield 75%; mp.170-
1
172°C; ir 3320-3381 (ꢀNH), 1709 (ꢀC=O); H-NMR ꢁ1.95(s, 3H,
CH3), 2.48(s, 3H, CH3), 4.42(s, 2H, NH2), 7.20-7.95(m, 8H,
ArH), 9.48(s, 1H, =CH). Anal. Calcd. for C17H17N5O (307.31):
C, 66.43; H, 5.53; N, 22.77; Found: C, 66.04; H, 5.28; N, 22.42.
4-[(4-Amino-benzylidene)-amino]-5-methyl-2-(3-chloro)-
phenyl-3H-[1,2,4]-triazol-3-one (3e). Yield 80%; mp.152-154
°C; ir 3326-3388 (ꢀNH), 1709 (ꢀ=O); 1H-NMR ꢁ 2.50(s, 3H, CH3),
4.50(s, 2H, NH2), 7.28-7.86(m, 8H, ArH), 9.48(s, 1H, =CH).
Anal. Calcd. for C16H14ClN5O (327.77): C, 58.62; H, 4.27 N,
21.35; Found: C, 58.23; H, 3.98; N, 21.01.
3-{2-[(2-(4-Methyl)phenyl-5-methyl-3H-[1,2,4]-triazol-3-
one-4-yl)]-iminophenyl}-pentane-2,4-dione (4d). Yield 78%;
1
mp.164-166°C; ir 3434 (ꢀNH), 1709 (ring ꢀC=O), 1674 (ꢀC=O); H-
NMR ꢁ 2.00(s, 3H, CH3), 2.38-2.42(2s, 6H, COCH3), 2.48(s,
3H, ring CH3), 7.50-8.00(m, 8H, ArH), 9.68(s, 1H, =CH),
14.00(s, 1H, NH). Anal. Calcd. for C22H22N6O3 (418.81): C,
63.08; H, 5.25; N, 20.05; Found: C, 62.77; H, 4.90; N, 19.88.
3-{2-[(2-(3-Chloro)phenyl-5-methyl-3H-[1,2,4]-triazol-3-one-
4-yl)]-iminophenyl}-pentane-2,4-dione (4e). Yield 78%; mp.
4-[(4-Amino-benzylidene)-amino]-5-methyl-2-(4-chloro)-
phenyl-3H-[1,2,4]-triazol-3-one (3f). Yield 85%; mp.120-
1
122°C; ir 3320-3375 (ꢀNH), 1709 (ꢀC=O); H-NMR ꢁ 2.45(s, 3H,
1
205-207°C; ir 3436 (ꢀNH), 1709 (ring ꢀC=O), 1678 (ꢀC=O); H-
CH3), 3.27(s, 3H, OCH3), 4.48(s, 2H, NH2), 7.25-7.98(m, 8H,
ArH), 9.50(s, 1H, =CH). Mass calcd for C16H14ClN5O: 327.77
& 329.77. Found: 327&329. Anal. Calcd. for C16H14ClN5O(327.77):
C, 58.62; H, 4.27; N, 21.35; Found: C, 58.28; H, 3.99; N, 20.95.
4-[(4-Amino-benzylidene)-amino]-5-methyl-2-(4-methoxy)-
phenyl-3H-[1,2,4]-triazol-3-one (3g). Yield 70%; mp. 120-
NMR ꢁ 2.38-2.40(2s, 6H, COCH3), 2.50(s, 3H, ring CH3), 7.40-
8.00(m, 8H, ArH), 9.65(s, 1H, =CH), 14.00(s, 1H, NH). Anal.
Calcd. for C21H19ClN6O3 (438.32): C, 57.54; H, 4.33; N, 19.16;
Found: C, 57.05; H, 4.09; N, 18.84.
3-{2-[(2-(4-Chloro)phenyl-5-methyl-3H-[1,2,4]-triazol-3-
one-4-yl)]-iminophenyl}-pentane-2,4-dione (4f). Yield 80%;
1
122°C; ir 3320-3375 (ꢀNH), 1709 (ꢀC=O); H-NMR ꢁ 2.45(s, 3H,
1
mp.260-262°C; ir 3438 (ꢀNH), 1709 (ring ꢀC=O), 1678 (ꢀC=O); H-
CH3), 3.27(s, 3H, OCH3) 4.48(s, 2H, NH2), 7.25-7.98(m, 8H,
ArH), 9.50(s, 1H, =CH). Mass calcd for C17H17N5O: 323.45.
Found: 323. Anal. Calcd. for C17H17N5O(323.45): C, 63.12; H,
5.25; N, 21.64; Found: C, 62.81; H, 5.01; N, 21.24.
NMR ꢁ 2.40-2.42(2s, 6H, COCH3), 2.55(s, 3H, ring CH3), 7.50-
8.00(m, 8H, ArH), 9.70(s, 1H, =CH), 14.00(s, 1H, NH). Mass
calcd for C21H19ClN6O3: 438.32 & 440.32 Found: 438&440.
Anal. Calcd. for C21H19ClN6O3(438.32): C, 57.54; H, 4.33; N,
19.16; Found: C, 57.08; H, 4.05; N, 18.75.
4-[(4-Amino-benzylidene)-amino]-5-methyl-2-(3-chloro-4-
methyl)phenyl-3H-[1,2,4]-triazol-3-one (3h). Yield 78%; mp.
1
3-{2-[(2-(4-Methoxy)phenyl-5-methyl-3H-[1,2,4]-triazol-3-
one-4-yl)]-iminophenyl}-pentane-2,4-dione (4g). Yield 70%;
120-122°C; ir 3315-3370 (ꢀNH), 1709 (ꢀC=O); H-NMR ꢁ 1.77(s,
3H, CH3), 2.38(s, 3H, CH3), 4.52(s, 2H, NH2), 7.20-7.76(m, 8H,
ArH), 9.40(s, 1H, =CH). Anal. Calcd For C17H16ClN5O
1
mp. 244-246°C; ir 3440 (ꢀꢀNH), 1709 (ring ꢀC=O), 1674(ꢀC=O); H-

Jan-Feb 2007
Azopyrazolobenzylidene Derivatives of 4-Amino-1,2,4-triazol-3-ones
5
4-{[4-(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl] benzylidene}-
amino-2-(4-methoxy)phenyl-5-methyl-3H-[1,2,4]-triazol-3-
one (5g). Yield 75%; mp. 138-140°C; ir 3212(ꢁNH), 1709 (ring
NMR ꢀ 2.42-2.44(2s, 6H COCH3), 2.50(s, 3H, ring CH3),
3.40(S,3H,OCH3), 7.43-7.94(m, 8H, ArH), 9.75(s, 1H, =CH),
13.90(s, 1H, NH). Mass calcd for C22H22N6O4: 439.81. Found: 434.
Anal. Calcd. for C22H22N6O4( 439.81): C, 60.76; H, 5.05; N,
19.31; Found: C, 60.47; H, 4.76; N, 19.06.
1
ꢁC=O); H-NMR ꢀ 2.45-2.50(2s, 6H, CH3), 2.48(s, 3H, ring CH3),
3.25(s, 3H,CH3), 7.55-8.00(m, 8H, ArH), 9.75(s, 1H, =CH), 12.98(s,
1H, NH). Mass calcd for C22H22N8O2: 430.84. Found: 430. Anal.
Calcd. for C22H22N8O2(430.84): C, 61.32; H, 5.10; N, 25.99;
Found: C, 58.01; H, 4.82; N, 25.77.
4-{[4-(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl] benzylidene}-
amino-2-(3-chloro-4-methyl)phenyl-5-methyl-3H-[1,2,4]-
triazol-3-one (5h). Yield 78%; mp.160-162°C; ir 3210(ꢁNH),
1709 (ring ꢁC=O); 1H-NMR ꢀ 1.88(s, 3H, CH3), 2.35-2.42(2s, 6H,
CH3), 2.45(s, 3H, ring CH3), 7.48-8.00(m, 8H, ArH), 9.70(s, 1H,
=CH), 12.88(s, 1H, NH). Anal. Calcd. for C22H21ClN8O
(449.37): C, 58.79; H, 4.67; N, 24.92; Found: C, 58.48; H, 4.32;
N, 24.66.
3-{2-[(2-(3-Chloro-4-methyl)phenyl-5-methyl-3H-[1,2,4]-
triazol-3-one-4-yl)]-iminophenyl}-pentane-2,4-dione (4h).
Yield 78%; mp.190-192°C; ir 3430 (ꢁH), 1709 (ring ꢁC=O), 1670
1
(ꢁC=O); H-NMR ꢀ 2.44-2.48(2s, 6H COCH3), 2.48(s, 3H, ring
CH3), 7.40-8.10(m, 8H, ArH), 9.85(s, 1H, =CH), 14.00(s, 1H, NH).
Anal. Calcd. for C22H21ClN6O3 (453.26): C, 58.29; H, 4.63; N,
18.53; Found: C, 58.01; H, 4.26; N, 18.19.
General Procedure for Preparation of 4-{[4-(3,5-Dimethyl-
1H-pyrazol-4-yl)diazenyl]benzylidene}amino-2-aryl-5-methyl-
3H-[1,2,4]-triazol-3-ones (5 a-h). Diones (4a-h) (0.438 g,
0.001 mol) and hydrazine hydrate 99% (0.2 ml, 0.004 mol) in
ethanol (15 ml) were refluxed on a water- bath for 8 hours. The
solid obtained after cooling was filtered and washed with hot
ethanol to get (5a); Yield 70%; mp. 150-152°C; ir 3210 (ꢁNH),
1709 (ring ꢁC=O); 1H-NMR ꢀ 2.44-2.48(2s, 6H, CH3), 2.55(s, 3H,
ring CH3), 7.55-8.04(m, 8H, ArH), 9.76(s, 1H, =CH), 13.00(s,
1H, NH). Mass calcd for C21H20N8O: 400.67. Found: 400.
Anal. Calcd. for C21H20N8O(400.67): C, 62.94; H, 4.99; N,
27.95; Found: C, 62.69; H, 4.72; N, 27.68.
General Procedure for Preparation of N-{[4-(2-Aryl-
methyl-3H-[1,2,4]-triazol-3-one-4-yl)]-iminophenyl}-aceta-
mides (6a-h). Amino compounds (3a-h) (0.438 g, 0.001 mol)
in excess of acetic anhydride were heated on a water- bath
for 3 hours and then poured into ice cold water. The resulting
N-acetyl derivative was filtered and washed with water and
crystallised from ethanol; yield 75%; mp.124-126°C; ir 3320
1
(ꢁNH), 1709 (ring ꢁC=O), 1678 (ꢁC=O); H-NMR ꢀ 2.10(s, 3H,
COCH3), 2.40(s, 3H, ring CH3), 7.46-7.85(m, 8H, ArH),
9.60(s, 1H, =CH), 10.03(s, 1H, NH). Mass calcd for C18H17-
N5O2: 335.16. Found: 335. Anal. Calcd. for C18H17-
N5O2(335.16): C, 64.50; H, 5.07; N, 20.88; Found: C, 64.12;
H, 4.81; N, 20.58.
4-{[4-(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl]benzylidene}-
amino-2-(4-bromo)phenyl-5-methyl-3H-[1,2,4]-triazol-3-one
(5b). Yield 80%; mp.186-188°C; ir 3218 (ꢁNH), 1709 (ring
ꢁC=O); 1H-NMR ꢀ 2.40-2.46(2s, 6H, CH3), 2.53(s, 3H, ring CH3),
7.55-8.00(m, 8H, ArH), 9.80(s, 1H, =CH), 13.00(s, 1H, NH).
Mass calcd for C21H19 BrN8O: 479.10 & 481.10. Found:
479&481. Anal. Calcd. for C21H19 BrN8O (479.10): C, 52.64;
H, 3.96; N, 23.37; Found: C, 52.35; H, 3.59; N, 23.04.
N-{[4-(2-(4-Bromo)phenyl-methyl-3H-[1,2,4]-triazol-3-one-
4-yl)]-iminophenyl}-acetamide (6b). Yield 80%; mp. 182-
1
184°C; ir 3318 (ꢁNH), 1709 (ring ꢁꢀC=O), 1676 (ꢁC=O); H-NMR ꢀ
2.10(s, 3H, COCH3), 2.53(s, 3H, ring CH3), 7.45-7.90(m, 8H,
ArH), 9.64(s, 1H, =CH), 10.05(s, 1H, NH). Mass calcd for
C18H16 BrN5O2: 414.16 & 416.16. Found: 414&416. Anal.
Calcd. for C18H16 BrN5O2(414.16):C, 52.19; H, 3.86; N, 16.90;
Found: C, 51.82; H, 3.56; N, 16.74.
4-{[4-(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl] benzylidene}-
amino-2-(3-methyl)phenyl-5-methyl-3H-[1,2,4]-triazol-3-ones
(5c). Yield 70%; mp.160-162°C; ir 3208 (ꢁNH), 1709 (ring
ꢁC=O); 1H-NMR ꢀ 2.00(s, 3H, CH3), 2.38-2.44(2s, 6H, CH3),
2.45(s, 3H, ring CH3), 7.40-7.90(m, 8H, ArH), 9.70(s, 1H,
=CH), 12.90(s, 1H, NH). Anal. Calcd. for C22H22N8O( 414.21 ):
C, 63.78; H, 5.31; N, 27.03; Found: C, 63.45; H, 5.05; N, 26.74.
4-{[4-(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl] benzylidene}-
amino-2-(4-methyl)phenyl-5-methyl-3H-[1,2,4]-triazol-3-one
(5d). Yield 78%; mp. 140-142°C; ir 3215 (ꢁNH), 1709 (ring
ꢁC=O); 1H-NMR ꢀ 2.03(s, 3H, CH3), 2.40-2.46(2s, 6H, CH3),
2.50(s, 3H, ring CH3), 7.45-8.00(m, 8H, ArH), 9.74(s, 1H,
=CH), 12.94(s, 1H, NH). Mass calcd for C22H22N8O: 414.21.
Found: 414. Anal. Calcd. for C22H22N8O: ( 414.21):C, 63.78; H,
5.31; N, 27.03; Found: C, 63.38; H, 5.08; N, 26.67.
N-{[4-(2-(3-Methyl)phenyl-methyl-3H-[1,2,4]-triazol-3-one-
4-yl)]-iminophenyl}-acetamide (6c). Yield 75%; mp. 170-
1
172°C; ir 3308 (ꢁNH), 1709 (ringꢁC=O;), 1676 (ꢁC=O); H-NMR ꢀ
1.82(s, 3H, CH3), 2.05(s, 3H, COCH3), 2.40(s, 3H, ring CH3),
7.40-7.88(m, 8H, ArH), 9.50(s, 1H, =CH), 9.80 (s, 1H, NH).
Anal. Calcd. for C19H19N5O2( 349.17 ): C, 65.35; H, 5.44; N,
20.04; Found: C, 65.02; H, 5.16; N, 19.74.
N-{[4-(2-(4-Methyl)phenyl-methyl-3H-[1,2,4]-triazol-3-one-
4-yl)]-iminophenyl}-acetamide (6d). Yield 78%; mp. 154-
1
156°C; ir 3310 (ꢁNH), 1709 (ringꢁC=O;), 1678 (ꢁC=O); H-NMR ꢀ
1.85(s, 3H, CH3), 2.07(s, 3H, COCH3), 2.43(s, 3H, ring CH3),
7.50-7.85(m, 8H, ArH), 9.57(s, 1H, =CH), 9.85(s, 1H, NH).
Mass calcd for C19H19N5O2: 349.17. Found: 349. Anal. Calcd.
for C19H19N5O2(349.17): C, 65.35; H, 5.44; N, 20.04; Found: C,
59.81; H, 5.05; N, 19.79.
4-{[4-(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl] benzylidene}-
amino-2-(3-chloro)phenyl-5-methyl-3H-[1,2,4]-triazol-3-one
(5e). Yield 75%; mp.144-146°C; ir 3210 (ꢁNH), 1709 (ring ꢁC=O);
1H-NMR ꢀ 2.35-2.40(2s, 6H, CH3), 2.50(s, 3H, ring CH3), 7.55-
8.00(m, 8H, ArH), 9.70(s, 1H, =CH), 12.86(s, 1H, NH). Anal.
Calcd. for C21H19 ClN8O( 434.5): C, 58.04; H, 4.37; N, 25.77;
Found: C, 57.74; H, 4.15; N, 25.53.
N-{[4-(2-(3-Chloro)phenyl-methyl-3H-[1,2,4]-triazol-3-one-
4-yl)]-iminophenyl}-acetamide (6e). Yield 80%; mp. 184-
1
186°C; ir 3315 (ꢁNH), 1709 (ringꢁC=O;), 1672 (ꢁC=O); H-NMR ꢀ
4-{[4-(3,5-Dimethyl-1H-pyrazol-4-yl)diazenyl] benzylidene}-
amino-2-(4-chloro)phenyl-5-methyl-3H-[1,2,4]-triazol-3-one (5f).
2.07(s, 3H, COCH3), 2.48(s, 3H, ring CH3), 7.45-7.90(m, 8H,
ArH), 9.60(s, 1H, =CH), 10.03(s, 1H, NH). Anal. Calcd. for
C18H16 ClN5O2 ( 369.61 ): C, 58.48; H, 4.32; N, 18.93; Found: C,
58.06; H, 4.06; N, 18.64.
1
Yield 78%; mp.22o-222°C; ir 3215 (ꢁNH), 1709 (ring ꢁC=O); H-
NMR ꢀ 2.40-2.47(2s, 6H, CH3), 2.55(s, 3H, ring CH3), 7.55-
8.00(m, 8H, ArH), 9.75(s, 1H, =CH), 12.90(s, 1H, NH). Mass
calcd for C21H19ClN8O: 435&437. Found: 434.5 & 436.5. Anal.
Calcd. for C21H19 ClN8O(434.5): C, 58.04; H, 4.37; N, 25.77;
Found: C, 57.55; H, 4.01; N, 25.51.
N-{[4-(2-(4-Chloro)phenyl-methyl-3H-[1,2,4]-triazol-3-one-
4-yl)]-iminophenyl}-acetamide (6f). Yield 85%; mp. 190-
1
192°C; ir 3320 (ꢁNH), 1709 (ringꢁC=O;), 1670 (ꢁC=O); H-NMR ꢀ

6
V. A. Sunagar, P. R. Latthe and B. V. Badami
Vol 44
2.15(s, 3H, COCH3), 2.50(s, 3H, ring CH3), 7.45-7.90(m, 8H,
ArH), 9.65(s, 1H, =CH), 10.10(s, 1H, NH). Mass calcd for
C18H16 ClN5O2: 369.61 & 371.61 Found: 369&371. Anal. Calcd.
for C18H16 ClN5O2(369.61): C, 58.48; H, 4.32; N, 18.93; Found:
C, 58.10; H, 3.95; N, 18.58.
REFERENCES
[1] J. R. Kavali, O. Kotresh and B. V. Badami, J. Chem.
Res.(S), 275-278 (2003).
[2] Unpublished work, Ph.D. thesis, Karnatak University
(2003).
[3] M. L. Werbal and N. W. Elslager, J. Med. Chem., 11, 411
(1968).
N-{[4-(2-(4-Methoxy)phenyl-methyl-3H-[1,2,4]-triazol-3-
one-4-yl)]-iminophenyl}-acetamide (6g). Yield 75%; mp. 142-
1
144°C; ir 3312 (ꢀNH), 1709 (ring ꢀC=O), 1676 (ꢀC=O); H-NMR ꢁ
[4] H. G. Garg and C. Prakash, J. Med. Chem., 14, 175
(1971).
2.10(s, 3H, COCH3), 2.40(s, 3H, ring CH3), 3.52(s, 3H, OCH3),
7.50-7.90(m, 8H, ArH), 9.58(s, 1H, =CH), 9.90(s, 1H, NH).
Mass calcd for C19H19N5O3: 365.16. Found: 365. Anal. Calcd.
for C19H19N5O3 (365.16): C, 62.49; H, 5.20; N, 19.16; Found: C,
62.14; H, 4.85; N, 18.88.
[5] O’ Sullivan and M.L. Conalty, Proc. R. Ir. Acad., 80B,
385-394 (1980).
[6] V. Dhingra, R. Bhatawdekar, L. Agarwal and V. S. Jolly,
J. Indian chem. Soc., 68, 672 (1991).
[7] V. S. Jolly, A. K. Srivastava, S. P. Singh and K. S.
Tiwari, J. Indian chem. Soc., 57(5), 539-541 (1980); Chem. Abstr.,
93, 169640w (1980).
[8] R. D. Naik and K. R. Desai, Orient. J. Chem., 14(1), 161-
162 (1998).
[8a] T. Miyazawa and H.Kurose, Jpn. Kokai Tokyo Koho
Hiroshi JP, 158,802 (2001).
[9] S. Thamotharan, V. Parthasarathi, V. Sunagar, B. V.
Badami and A. Linden, Acta. Cryst., E59, o1272-o1274 (2003).
[10] J. J. P Stewart, MOPAC 2000, Fujitsu Limited, Tokyo,
Japan (1999).
N-{[4-(2-(3-Chloro-4-methyl)phenyl-methyl-3H-[1,2,4]-
triazol-3-one-4-yl)]-iminophenyl}-acetamide (6h). Yield 80%;
mp. 182-184°C; ir 3318 (ꢀNH), 1709 (ring ꢀC=O), 1676 (ꢀC=O); 1H-
NMR ꢁ 2.10(s, 3H, COCH3), 2.53(s, 3H, ring CH3), 7.45-
7.90(m, 8H, ArH), 9.64(s, 1H, =CH), 10.05(s, 1H, NH). Mass
calcd for C19H18 ClN5O2: 383.62 &385.62. Found: 383&385.
Anal. Calcd. for C19H18 ClN5O2(383.62): C, 59.48; H, 4.69; N,
18.24; Found: C, 59.14; H, 4.45; N, 17.88.
Acknowledgment. We thank Dr. G. S. Puranik, retired
Professor of Organic Chemistry and former Chairman,
Department of Chemistry, Karnatak University, Dharwad, for
encouragement and suggestions.
[11] M. J. S. Dewar, E.G. Zoebisch, E. F. Healy, and J. J. P
Stewart, J. Am. Chem. Soc., 107, 366 (1985).
[12] J. J. P Stewart, J. Comput. Chem., 10, 209 (1989).