New synthetic approaches to substituted pyridine-2-(1 h)-ones clubbed with substituted aryl diazo substituents

Article abstract of DOI:10.1080/00397911.2011.630771

6-Triazolylpyridone derivatives were synthesized by coupling 4-(4-methoxyphenyl)-6-(1H-1,2,4-triazol-1-yl)-1-(3-chlorophenyl)pyridin-2(1H) -one with substituted benzenediazonium chlorides in the form of two isomers, which were separated by column chromato

Full text of DOI:10.1080/00397911.2011.630771

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New Synthetic Approaches to
Substituted Pyridine-2-(1H)-ones
Clubbed with Substituted Aryl Diazo
Substituents
Navin B. Patel a & Rakesh D. Sharma a
a Department of Chemistry, Veer Narmad South Gujarat University,
Surat, India
Version of record first published: 21 Feb 2013.
To cite this article: Navin B. Patel & Rakesh D. Sharma (2013): New Synthetic Approaches to
Substituted Pyridine-2-(1H)-ones Clubbed with Substituted Aryl Diazo Substituents, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
43:9, 1250-1262
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Synthetic Communications1, 43: 1250–1262, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.630771
NEW SYNTHETIC APPROACHES TO SUBSTITUTED
PYRIDINE-2-(1H)-ONES CLUBBED WITH SUBSTITUTED
ARYL DIAZO SUBSTITUENTS
Navin B. Patel and Rakesh D. Sharma
Department of Chemistry, Veer Narmad South Gujarat University,
Surat, India
GRAPHICAL ABSTRACT
Abstract 6-Triazolylpyridone derivatives were synthesized by coupling 4-(4-methoxyphenyl)-
6-(1H-1,2,4-triazol-1-yl)-1-(3-chlorophenyl)pyridin-2(1H)-one with substituted benzene-
diazonium chlorides in the form of two isomers, which were separated by column chromato-
graphy and characterized by 1H and 13C NMR. Following the green approach, solvents were
avoided as much as possible. The reaction monitoring was carried out by gas chromatography
as well as thin-layer chromatography. The scope and limitation of the method are discussed.
The structures of all the compounds have been assigned unambiguously on the basis of elemen-
tal analysis, infrared, and NMR spectral data and have been evaluated for antimicrobial and
antitubercular activities.
Keywords Aryldiazonium chlorides; b-aryl glutaconic acid; microbial activity; 2-pyridones;
1,2,4-triazole
Received July 3, 2011.
Address correspondence to Navin B. Patel, Department of Chemistry, Veer Narmad South Gujarat
University, Udhna Magdalla Road, Surat 395007, India. E-mail: drnavin@satyam.net.in
1250

2-(1H)-PYRIDONES WITH ARYL DIAZO
1251
INTRODUCTION
The heterocyclic skeleton containing nitrogen atoms is the basis of many essen-
tial pharmaceuticals and of many physiologically active natural products. 2-Pyri-
done is a nitrogen containing synthetically designed scaffold with a broad
spectrum of biological activities. Its derivatives have been claimed to be nonnucleo-
side HIV type I specific reserve transcriptase inhibitors[1] and anti-inflammatory
agents.[2] The 2-pyridone moiety frequently found in a variety of interesting com-
pounds has received remarkable attention because of its promising features as a
key scaffold and in privileged building blocks.[3] A wide range of biological activities
has been observed in compounds possessing a 2-pyridone motif, including antitu-
mor,[4] antifungal,[5] antibacterial,[6] anti-inflammatory,[7] antiviral[8] and antithrom-
botic properties.[9] (20S)-Camptothecin is a well-known anticancer natural product
that was first isolated from Camptotheca acuminate in 1966.[10,11] 2-Pyridones act
as potent bacterial DNA gyrase inhibitors,[12] active cytotoxic agents as determined
in the in vitro L1210 screen,[13] and potent inhibitors of BaENR.[14] 3-Acetoxy-2-pyr-
idone had reproducible activity against murine P-388 lymphocytic leukemia.[15]
Table 1. Characterization data of compounds 1–26
C (%) #
N (%) #
H (%)
Comp. no.
R
M.R.
Mol. formula
18H14NO3Cl
Found Calcd. Found Calcd. Found Calcd.
1
2
–
206–208
C
66.05
62.42
63.49
64.69
66.04
62.42
63.48
64.67
60.36
60.36
60.36
65.26
65.26
65.26
59.15
59.15
59.15
63.22
64.67
60.36
60.36
60.36
65.26
65.26
65.26
59.15
59.15
59.15
63.22
60.07
4.27
4.07
4.28
4.05
4.31
4.07
4.02
3.97
3.51
3.51
3.51
4.26
4.26
4.26
3.44
3.44
3.44
3.97
3.97
3.51
3.51
3.51
4.26
4.26
4.26
3.44
3.44
3.44
4.11
3.98
4.31
4.08
4.00
3.93
3.56
3.54
3.55
4.24
4.21
4.20
3.47
3.44
3.49
3.93
3.94
3.55
3.52
3.57
4.29
4.31
4.25
3.49
3.45
3.48
4.13
3.95
–
179–181 C18H13NO2Cl2
170–172 20H15N4O2Cl
172–174 C26H19N6O2Cl
184–186
189–191 C26H18N6O2Cl2 60.38
196–198 26H18N6O2Cl2 60.36
3
–
C
14.78
17.39
16.24
16.25
16.25
16.91
16.90
16.91
18.58
18.58
18.56
16.39
17.39
16.27
16.24
16.25
16.90
16.92
16.94
18.55
18.58
18.55
16.38
21.33
14.81
17.40
16.24
16.24
16.24
16.91
16.91
16.91
18.57
18.57
18.57
16.38
17.40
16.24
16.24
16.24
16.91
16.91
16.91
18.57
18.57
18.57
16.38
21.32
4
H
o-Cl
5
C26H18N6O2Cl2 60.35
6
m-Cl
p-Cl
7
C
8
o-CH3
m-CH3
p-CH3
o-NO2
m-NO2
p-NO2
161–163 C27H21N6O2Cl
165–167 C27H21N6O2Cl
157–159 C27H21N6O2Cl
171–173 C26H18N7O4Cl
199–201 C26H18N7O4Cl
177–179 C26H18N7O4Cl
65.25
65.27
65.27
59.13
59.13
59.17
63.33
64.68
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
o-OCH3 167–169 C27H21N6O3Cl
H
o-Cl
152–154
194–196
C
C
26H19N6O2Cl
26H18N6O2Cl2 60.34
m-Cl
p-Cl
187–189 C26H18N6O2Cl2 60.37
209–211 C26H18N6O2Cl2 60.36
o-CH3
m-CH3
p-CH3
o-NO2
m-NO2
p-NO2
155–157 C27H21N6O2Cl
163–165 C27H21N6O2Cl
157–159 C27H21N6O2Cl
161–163 C26H18N7O4Cl
172–174 C26H18N7O4Cl
158–160 C26H18N7O4Cl
65.27
65.26
65.24
59.16
59.15
59.16
63.23
60.07
o-OCH3 177–179 C27H21N6O3Cl
182–184 C23H18N7O2Cl
–
# Satisfactory C, N, and H analysis were obtained for all the compounds.

1252
N. B. PATEL AND R. D. SHARMA
Table 2. Antimicrobial and antifungal activity data of 1–26
Minimal bactericidal concentration mg=mL
Gram negative
Gram positive
Minimal fungicidal concentration mg=Ml
Comp. no.
E. coli P. aeruginosa S. aureus S. pyogenes C. albicans
A. niger
A. clavatus
1
200
200
100
250
200
100
100
100
500
500
500
250
200
200
200
100
500
500
100
500
500
500
250
250
200
200
250
200
100
100
25
250
100
200
200
250
100
500
500
150
200
100
250
200
200
250
250
100
500
500
250
200
100
250
500
250
250
250
50
250
100
200
250
250
100
500
500
200
200
100
250
250
100
250
250
100
500
500
200
200
100
250
250
250
250
100
50
1000
500
500
200
500
250
1000
1000
500
250
500
500
200
250
500
250
250
100
250
500
250
250
500
500
500
250
–
1000
500
500
500
250
500
1000
1000
500
250
500
500
500
500
250
500
500
500
1000
500
250
500
500
>1000
500
500
–
1000
500
500
500
250
500
1000
1000
500
250
500
500
500
500
500
250
500
500
1000
500
500
250
500
500
500
250
–
2
3
4
62.5
5
100
500
500
200
250
200
100
200
6
7
8
9
10
11
12
13
14
62.5
500
250
250
500
100
200
250
200
200
250
250
250
250
100
25
15
16
17
18
19
20
21
22
23
24
25
26
Ampicillin
Ciprofloxacin
Greseofulvin
–
500
–
100
–
100
–
–
–
–
Girardet has synthesized and reported a new series of 1,2,4-triazoles tested
against several nonnucleoside reverse transcriptase inhibitor (NNRTI)–resistant
HIV-I isolutes.[16] and demonstrated its activity against malarial and bronchospasm.
It has activity as coronary, vasodilator, antihypertensive, antidepressive,[17] leishma-
nicidic, antibiotic, adenosine antagonist, immunosuppressant, antitumor, fungicidal,
Table 3. Anti-tuberculosis activity of selected compounds
Comp. No.
MIC values (mg =mL) of M. tuberculosis H37Rv
% Inhibition
2
10
250
250
12.5
125
40
99
98
98
99
98
11
12
Rifampicin

2-(1H)-PYRIDONES WITH ARYL DIAZO
1253
xanthine oxidase inhibitor, and anticonvulsant[18] agents. Triazoles possess signifi-
cant antifungal[19] and antiviral properties.[20] They are strong cemtral nervous sys-
tem depressant and mild to moderate anti-inflammatory, hypocholesterimic,
hypertensive, antimicrobial, and antibactacterial agents.[20–22] Amino acid ester func-
tional pyrazolyl compounds have also been reported as antifungal agents.[23]
A number of synthetic methods for the preparation of 2-pyridones have been
reported, and some of them have been used to obtain milrinone analogs with
improved activity.[24] 2-Pyridones were synthesized from cyanoacetamides and ene-
carbonyl compounds via chemo- and regioselective[25] tandem Blaise reaction of
nitriles with propiolates,[26] from fluoroquinolones,[27] and from annulation of
ketones and esters.[28] The most straightforward and versatile approach to N-aryl
pyridine-2-ones is the coupling reaction of pyridin-2-(1H)-one with highly
electron-deficient aryl halides through nucleophilic substitution.[29] Recently, N-ary-
lation of pyridine-2(1H)-ones with pentavalent organobismuth reagents to give
pyridine-2-ones under copper-free conditions was also reported.[30] A recent
approach to the synthesis of N-aryl substituted pyridones from b-aryl glutaconic acid
using aromatic amine prompted us to present our results in this field.
Keeping applications of 2-pyridones and 1,2,4-triazole in mind and in continu-
ation of our earlier work we have decided to synthesize 6-triazolyl-2(1H)-pyridinones
from b-aryl glutaconic acid.[31] Substituted 2-pyridones have been prepared by
nucleophilic substitution reactions using heterocyclic groups suca as triazolyl under
basic conditions. These substituted pyridinones have two nucleophilic positions, 3
and 5.[32] To check the nucleophilicity of these positions they were subjected to
electrophilic substitutions and then characterized by spectral data.[33,34] The purpose
of the present work was to observe the variation in antimicrobial properties after
structural changes.
RESULTS AND DISCUSSION
In continuation of our research on the synthesis of heterocyclic molecules using
diazotization, coupling, and Mannich reaction.[31] herein we report the studies of a facile
synthesis of the substituted 6-(1H-1,2,4-triazol-1-yl)-2(1H)-pyridinones via azo coupling
using column chromatography. The replacement of the carbonyl by chloro group was
confirmed by 13C NMR.; lower-field resonance at d 141.32 ppm was attributed to the
chloro group at C-6 in compound 2 in place of the carbonyl at 169.82 ppm in compound
1. Azo coupling of diazonium salts with compound 2 was confirmed by infrared(IR)
spectra, and a sharp band was observed near 1575cmꢀ1 due to the –N N– group. Most
=
excitingly, two azo-coupled products were obtained, which were separated by column
chromatography over activated silica gel using ethyl acetate–chloroform (70:30) as
mobile phase. Two compounds were characterized as 6-substituted-amino-
4-(4-methoxyphenyl)-1-(3-chlorophenyl)-3-(arylazo) pyridin-2(1H)-ones 4–14 and their
1
5-(arylazo) isomers 15–25 (Scheme 1), on the basis of spectral data.[35] In the H
NMR spectrum of 4-(4-methoxyphenyl)-1-(3-chlorophenyl)-3-(4-chlorophenylazo)-
6-triazolyl-2(1H)-pyridinone 7, a proton singlet was observed at 5.9 ppm due to a proton
at the C-5 position, whereas for 4-(4-methoxyphenyl)-1-(4-chlorophenylazo)-
5-(4-chlorophenylazo)-6-triazolyl-2(1H)-pyridinone 18, a proton singlet was observed
at 6.6 ppm due to a proton at the C-3 position.

1254
N. B. PATEL AND R. D. SHARMA
=
Scheme 1. R H, o-OCH3, o, m, p - Cl, CH3, NO2 Reagents and conditions: (a) POCl3, reflux (b) 1, 2, 4-
triazole, DMF, NaNo2, reflux (c) coupling with substituted aryldiazonium chlorides (d) mannich reaction.
After having checked the nucleophilicity at positions 3 and 5, the Mannich reac-
tion was also carried out on compounds 3 using a secondary amine as 1,2,4-triazole.
The compound that resulted, 26, proves that position 3 is more nucleophilic than 5.[24]
Limitation
In our present study we synthesized 6-triazolyl-2(1H)-pyridinone from b-aryl
glutaconic acid, which was synthesized from citric acid, but poor yield of b-aryl
glutaconic acid is a major limitation of the method.
Microbial and Antitubercular Studies
The experimental testing of antibacterial studies[30,36,37] did not show compara-
ble results with standard drug cefoperazone against the two Gram-positive (S. aureus

2-(1H)-PYRIDONES WITH ARYL DIAZO
1255
and B. subtilius) and two Gram-negative (E. coli and P. vulgarius) bacteria, and an
antifungal study was done for three fungal species, C. albicans, A. niger, and A. cla-
vatus and compared with the standard drug greseofulvin. All synthesized compounds
showed moderate to good activity except 6, 13, 19, and 24, which showed poor
activity. The compounds 2, 4, 5, 6, 7, 10, 11, 13, 18, 21, 22, and 26 showed good
activity The active ones, 2, 10, 11, and 12, were further tested in a secondary screen-
ing against Mycobacterium tuberculosis H37Rv in Lowenstein–Jensen (LJ) medium
(conventional method) and displayed good antitubercular activity when compared
with the standard drug rifampicin at 40 mg=ml.
CONCLUSION
In summary, we have demonstrated an efficient method for the synthesis of
substituted 6-(4H-1,2,4-triazol-4-yl)-2(1H)-pyridinones via azo coupling in the form
of two isomers, which were separated by column chromatography. The reactions
were clean, and the products were obtained in good yields without the formation
of any side products. The synthesized compounds showed moderate to good
antimicrobial and antitubercular activity.
EXPERIMENTAL
Melting points were determined by means of the open capillary method and are
uncorrected. IR spectra (KBr pellets) were recorded on a Thermo Scientific spectrophot-
1
ometer. H NMR spectra were recorded in CDCl3 on a Bruker Avance II 400-MHz
instrument using tetramethylsilane (TMS) as internal standard. Elemental analyses were
performed by means of a Heraeus CHN rapid analyzer; their results agreed satisfactorily
with the calculated values. All reactions were monitored by thin-layer chromatography
(TLC) on aluminum sheets (silica gel 60-F254, E. Merck). Compounds were visualized by
ultraviolet (UV) light or by dipping the solution containg 5% KMnO4 solution. Column
chromatography was carried out using silica gel (100–200 mesh).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)pyridine-2,6-(1H,5H)-dione 1
A mixture of 3-(4-methoxyphenyl)-2,3-ene-pentanedioic acid (2.4 g, 0.1 mol)
and m-chloroaniline (11.2 g, 0.1 mol) was slowly heated in an oil bath at 220 ꢁC
for 1 hr. It was cooled to room temperature and crystallized from absolute alcohol
to obtain a pale yellow crystalline product 2, yield 23.0 g (78.5%); IR (KBr, cmꢀ1):
=
=
3020 (C-H, C-H), 1620 (C C), 1240 (C-O-C), 1675 & 1600 (C O), 1510 (-N-Ph);
1H NMR (400 MHz, CDCl3): 2.57 (s, 2H, -CH2), 3.88 (s, 3H, -OCH3), 6.64 (s,
1H, C3-H pyridone), 6.74–7.92 (m, 8H, Ar-H); 13C NMR (100 MHz, CDCl3) d:
36.4, 63.8, 115.1, 121.3, 124.2, 127.0, 127.5, 128.1, 129.1, 129.6, 134.8, 135.5,
151.7, 161.6, 165.6, 169.8; MS: m=z ¼ 327.77 (Mþ).
6-Chloro-4-(4-methoxyphenyl)-1-(3-chlorophenyl)-pyridin-2(1H)-one 2
A mixture of 1 (3.28 g, 0.01 mol) and phosphorous oxychloride (9 ml) was
refluxed for 1 h and poured onto crushed ice, when 2 was obtained as solid. It was

1256
N. B. PATEL AND R. D. SHARMA
crystallized from ethanol, yield 2.5 g (79.26%); IR (KBr): 3000 (C-H), 3030 (C-H),
1
=
=
1620 (C C), 1260 (C-O-C), 1700 (C O), 1520 (-N-Ph), 1040 (Ar-Cl); H NMR
(400 MHz, CDCl3): 3.64 (s, 3H, -OCH3), 5.97 (s, 1H, C5-H pyridone), 6.64 (s, 1H,
C3-H pyridone), 6.69–7.52 (m, 8H, Ar-H); 13C NMR (100 MHz, CDCl3) d: 63.7,
106.0, 114.2, 115.0, 120.6, 128.1, 128.5, 129.2, 129.5, 131.8, 137.4, 138.1, 141.3,
151.3, 160.6, 163.6; MS: m=z ¼ 346.21 (Mþ), 348.21 (Mþ þ 2), 350.21 (Mþ þ 4).
4-(4-Methoxyphenyl)-6-(1H-1,2,4-triazol-1-yl)-1-(3-chlorophenyl)
pyridin-2(1H)-one 3
A mixture of 2 (3.47 g, 0.01 mol) and 1,2,4-triazole(0.69 g, 0.01 mol) was
refluxed for 12 h in dimethylformamide (DMF) and thereafter the reaction mass
was poured in acidic crushed ice and then resultant solid was filtered, washed with
water and crystallized from acetone to get 3. Yield 2.7 g (69.40%); IR (KBr):
=
1
(1665 > C O); H NMR (400 MHz, CDCl3): 3.67 (s, 3H, -OCH3), 5.90 (s, 1H, C5-
H pyridone), 6.68 (s, 1H, C3-H pyridone), 6.69–7.52 (m, 8H, Ar-H), 8.39 (s, 2H,
C3-H & C5-H triaz.); 13C NMR (100 MHz, CDCl3) d: 55.9, 84.6, 114.3, 118.9,
119.7, 121.1, 122.0, 124.5, 129.8, 129.8, 130.4, 134.2, 134.5, 138.8, 139.0, 146.0,
151.0,160.7, 160.7; MS: m=z ¼ 378.82 (Mþ), (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3/5-(substitutedphenylazo)-6-
(1H-1,2,4-triazol-1-yl)-pyridin-2(1H)-one 4–14 and 15–25
A precooled (0–5 ꢁC) solution of benzenediazonium chloride [prepared by
diazotizing substituted aniline (0.01 mol) in 6 ml of 1:1 HCl with NaNO2 (0.69 g,
0.01 mol) in 10 ml water] was added to a precooled (0–5 ꢁC) solution of 3
(0.01 mol) in 100 ml acetone. The reaction mixture was poured in 200 ml water
and then basified with diluted NaOH. The colored product was filtered, washed with
water, and dried. Two azo-coupled products were obtained, which were separated by
column chromatography over activated silica gel using ethyl acetate–chloroform
(70:30) as mobile phase.
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(phenylazo)-6-(1H-1,2,4-
triazol-1-yl)-pyridin-2(1H)-one 4 (C26H19N6O2Cl). IR (KBr): 1260 (C-O-C), 1650
1
=
=
(>C O), 1570 (-N N-), 1435 (C-N), 3010 & 2920 (C-H str); H NMR (400 MHz,
CDCl3): 3.9–4.0 (q, 3H, OCH3), 5.9 (s, 1H, C5-H), 7.0–7.7 (m, 13H, Ar-H),
8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 55.9, 84.6, 114.3, 114.5,
119.7, 121.1, 122.1, 124.0, 124.5, 128.7, 128.8, 128.8, 128.8, 128.8, 128.8, 128.9,
128.9, 130.4, 134.2, 134.5, 139.0, 146.0, 146.5, 151.1, 158.4 160.7; MS: m=
z ¼ 428.13 (Mþ), 430.13 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(2-chlorophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 5 (C26H18N6O2Cl2). IR (KBr): 1250 (C-O-
1
=
=
C), 1660 (>C O), 1575 (-N N-), 1425 (C-N), 3020 & 2910 (C-H str); H NMR
(400 MHz, CDCl3): 3.9–nbsp;4.0 (q, 3H, OCH3), 6.0 (s, 1H, C5-H), 7.0–7.7 (m,
12H, Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 55.9, 84.6,
114.3, 114.3, 119.7, 121.1, 122.0, 124.1, 124.5, 126.9, 128.9, 129.0, 129.8, 129.8,

2-(1H)-PYRIDONES WITH ARYL DIAZO
1257
130.2, 130.2, 130.4, 134.2, 134.3, 134.5, 139, 146.2, 146.5, 151.0, 158.4, 160.7; MS: m=
z ¼ 516.09 (Mþ), 518.09 (Mþ þ 2), 520.09 (Mþ þ 4).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(3-chlorophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 6 (C26H18N6O2Cl2). IR (KBr): 1250 (C-O-
1
=
=
C), 1670 (>C O), 1575 (-N N-), 1420 (C-N), 3020 & 2915 (C-H str); H NMR
(400 MHz, CDCl3): 3.9–4.0 (q, 3H, OCH3), 6.0 (s, 1H, C5-H), 7.0–7.6 (m, 12H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 55.9, 84.6, 114.3,
114.4, 119.7, 121.1, 122.0, 123.9, 124.5, 126.9, 128.9, 129.1, 129.8, 129.8, 130.1,
130.2, 130.4, 134.2, 134.3, 134.5, 139.2, 146.1, 146.5, 151.0, 158.4, 160.7; MS: m=
z ¼ 516.09 (Mþ), 518.09 (Mþ þ 2), 520.09 (Mþ þ 4).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(4-chlorophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 7 (C26H18N6O2Cl2). IR (KBr): 3068 (Ar
=
C-H), 2976, 2929 (C-H), 1659 (C N), 1604 (C C), 1249 (C-O-C), 1714 (C O),
=
=
1
1560 (-N N-), 1511 (N -Ph); H NMR (400 MHz, CDCl3): 4.1 (s, 3H, -OCH3),
=
5.92 (s, 1H, C5-H pyridone), 6.66–7.52 (m, 12H, Ar-H), 8.39 (s, 2H, C3-H & C5-H
triaz); 13C NMR (100 MHz, CDCl3) d: 63.9, 88.7, 105.9, 114.2, 115.0, 199.3, 120.6,
122.9, 123.8, 128.1, 128.3, 128.5, 129.2, 129.5, 131.8, 134.5, 137.4, 138.1, 141.3,
145.9, 151.3, 154.9, 160.6, 163.6; MS: m=z ¼ 516.09 (Mþ), 518.09 (Mþ þ 2), 520.09
(Mþ þ 4).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(2-methylphenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 8 (C27H21N6O2Cl). IR (KBr): 1255 (C-O-C),
1655 (>C O), 1570 (-N N-), 1435 (C-N), 3030 & 2910 (C-H str); 1H NMR
(400 MHz, CDCl3): 2.3 (s, 3H, CH3), 3.9–4.1 (q, 3H, OCH3), 5.9 (s, 1H, C5-H),
7.0–7.7 (m, 12H, Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d:
15.2, 55.9, 84.6, 114.3, 114.3, 119.7, 121.1, 122.0, 124.0, 124.5, 125.8, 128.1, 128.7,
128.7, 129.1, 129.8, 129.8, 130.4, 134.2, 134.5, 137.1, 139.0, 146.2, 146.5, 151.0,
158.4, 160.7; MS: m=z ¼ 496.14 (Mþ), 498.14 (Mþ þ 2).
=
=
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(3-methylphenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 9 (C27H21N6O2Cl). IR (KBr): 1240 (C-O-C),
1660 (>C O), 1565(-N N-), 1420 (C-N), 3025 & 2915 (C-H str); 1H NMR
(400 MHz, CDCl3): 2.3 (s, 3H, CH3), 3.9–4.0 (q, 3H, OCH3), 6.0 (s, 1H, C5-H),
7.0–7.6 (m, 12H, Ar-H), 8.2–8.3 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d:
24.3, 55.9, 84.6, 114.3, 114.3, 119.7, 121.1, 122.0, 124.0, 124.5, 125.8, 128.6, 128.8,
129.1, 129.8, 129.8, 130.4, 130.4, 134.2, 134.5, 138.4, 139.0, 146.1, 146.5, 151.0,
158.4, 160.7; MS: m=z ¼ 496.14 (Mþ), 498.14 (Mþ þ 2).
=
=
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(4-methylphenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 10 (C27H21N6O2Cl). IR (KBr): 1250 (C-O-
1
=
=
C), 1650 (>C O), 1560 (-N N-), 1425 (C-N), 3010 & 2910 (C-H str); H NMR
(400 MHz, CDCl3): 2.3 (s, 3H, CH3), 3.9–4.0 (q, 3H, OCH3), 6.0 (s, 1H, C5-H),
7.0–7.7 (m, 12H, Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d:
24.3, 55.9, 84.6, 114.3, 114.3, 119.7, 121.1, 122.0, 124.0, 124.5, 125.7, 128.7, 128.7,
129.1, 129.1, 129.8, 129.8, 130.4, 134.2, 134.5, 138.4, 139.0, 146.0, 146.5, 151.1,
158.4, 160.7; MS: m=z ¼ 496.14 (Mþ), 498.14 (Mþ þ 2).

1258
N. B. PATEL AND R. D. SHARMA
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(2-nitrophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 11 (C26H18N7O4Cl). IR (KBr): 1245 (C-O-
1
=
=
C), 1660 (>C O), 1570 (-N N-), 1435 (C-N), 3020 & 2910 (C-H str), H NMR
(400 MHz, CDCl3): 3.9–4.0 (q, 3H, OCH3), 6.0 (s, 1H, C5-H), 7.0–7.7 (m, 12H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 55.9, 84.6, 114.3,
114.3, 119.7, 121.2, 121.1, 122.0, 124.0, 124.0, 124.5, 129.7, 129.7, 129.8, 129.8,
130.4, 134.2, 134.5, 134.9, 139.0, 141.2, 146.5, 148.0, 151.1, 158.4, 160.7; MS: m=
z ¼ 527.11 (Mþ), 529.11 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(3-nitrophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 12 (C26H18N7O4Cl). IR (KBr): 1260 (C-O-
1
=
=
C), 1655 (>C O), 1570 (-N N-), 1430 (C-N), 3020 & 2920 (C-H str); H NMR
(400 MHz, CDCl3): 3.8–3.9 (q, 3H, OCH3), 5.9 (s, 1H, C5-H), 7.0–7.7 (m, 12H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 55.9, 84.6, 114.3,
114.3, 119.7, 121.1, 121.1, 122.0, 124.0, 124.0, 124.5, 129.6, 129.7, 129.8, 129.8,
130.4, 134.2, 134.5, 134.9, 139.0, 146.1, 146.5, 148.0, 151.1, 158.5, 160.7; MS: m=
z ¼ 527.11 (Mþ), 529.11 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(4-nitrophenylazo)-6-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 13 (C26H18N7O4Cl). IR (KBr): 1250 (C-O-
1
=
=
C), 1650 (>C O), 1575 (-N N-), 1435 (C-N), 3010 & 2925 C-H str), H NMR
(400 MHz, CDCl3): 3.9–4.1 (q, 3H, OCH3), 5.9 (s, 1H, C5-H), 6.9–7.6 (m, 12H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 55.9, 84.6, 114.3,
114.3, 119.7, 121.1, 121.1, 121.1, 122.0, 124.0, 124.5, 129.7, 129.7, 129.8, 129.8,
130.4, 134.2, 134.5, 134.8, 139.0, 146.1, 146.5, 148.0, 151.0, 158.4, 160.7; MS: m=
z ¼ 527.11 (Mþ), 529.11 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-3-(2-methoxyphenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 14 (C27H21N6O3Cl). IR (KBr): 1255 & 1240
1
=
=
(C-O-C), 1670 (>C O), 1565 (-N N-), 1425 (C-N), 3020 & 2915 (C-H str); H
NMR (400 MHz, CDCl3): 3.8–4.0 (q, 6H, OCH3), 6.0 (s, 1H, C5-H), 7.0–7.7 (m,
12H, Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 55.9, 55.9,
84.6, 99.6, 114.3, 114.3, 114.3, 119.7, 121.1, 121.1, 122.0, 124.0, 124.5, 129.8,
129.8, 129.8, 129.9, 130.4, 134.2, 134.5, 139.0, 146.0, 146.5, 151.0, 158.4, 159.1,
160.7; MS: m=z ¼ 512.14 (Mþ), 514.14 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(phenylazo)-6-(1H-1,2,4-
triazol-1-yl)-pyridin-2(1H)-one 15 (C26H19N6O2Cl). IR (KBr): 1250 (C-O-C),
1660 (>C O), 1565 (-N N-), 1430 (C-N), 3020 & 2910 (C-H str); 1H NMR
(400 MHz, CDCl3): 4.0–4.1 (q, 3H, OCH3), 6.6 (s, 1H, C3-H), 7.0–7.7 (m, 13H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 50.1, 55.9, 85.0,
111.6, 112.5, 113.9, 114.3, 114.3, 117.3, 121.1, 128.5, 128.7, 128.8, 128.8, 128.8,
128.8, 128.9, 129.8, 129.8, 131.0, 135.1, 139.1, 145.8, 146.0, 151.0, 160.7; MS: m=
z ¼ 482.13 (Mþ), (Mþ þ 2).
=
=
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(2-chlorophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 16 (C26H18N6O2Cl2). IR (KBr): 1255(C-O-
C), 1650 (>C O), 1570(-N N-), 1420(C-N), 3025 & 2920(C-H str); 1H NMR
(400 MHz, CDCl3): 3.9–4.0 (q, 3H, OCH3), 6.7 (s, 1H, C3-H), 7.0–7.6 (m, 12H,
=
=

2-(1H)-PYRIDONES WITH ARYL DIAZO
1259
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 50.1, 55.9, 85.0, 111.6,
112.4, 113.9, 114.3, 114.5, 117.3, 121.2, 126.9, 128.5, 128.9, 129.0, 129.8, 129.8, 130.2,
130.2, 131.0, 134.3, 135.1, 139.0, 145.8, 146.1, 151.0, 160.7; MS: m=z ¼ 516.09 (Mþ),
518.09 (Mþ þ 2), 520.09 (Mþ þ 4).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(3-chlorophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 17 (C26H18N6O2Cl2). IR (KBr): 1240 (C-O-
1
=
=
C), 1655 (>C O), 1560 (-N N-), 1425 (C-N), 3025 & 2910 (C-H str); H NMR
(400 MHz, CDCl3): 3.9–4.0 (q, 3H, OCH3), 6.6 (s, 1H, C3-H), 7.0–7.7 (m, 12H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 50.1, 55.9, 85.0,
111.6, 112.4, 113.9, 114.3, 114.3, 117.3, 121.1, 126.9, 128.6, 128.9, 129.1, 129.8,
130.1, 130.2, 130.8, 134.3, 135.2, 139.1, 145.8, 146.2, 151.0, 160.7; MS: m=
z ¼ 516.09 (Mþ), 518.09 (Mþ þ 2), 520.09 (Mþ þ 4).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(4-chlorophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 18 (C26H18N6O2Cl2). IR (KBr): 3077 (Ar
=
C-H), 2979, 2925 (C-H), 1651 (C N), 1606 (C C), 1248 (C-O-C), 1712 (C O),
=
=
1
1572 (-N N-), 1511 (N-Ph); H NMR (400 MHz, CDCl3): 4.12 (s, 3H, OCH3),
=
6.67 (s, 1H, C3-H), 6.67–7.52 (m, 12H, Ar-H), 8.36 (s, 2H, C3-H & C5-H triaz);
13C NMR (100 MHz, CDCl3) d: 63.8, 89.7, 107.2, 114.2, 115.0, 115.4, 119.2, 120.6,
127.1, 127.8, 128.2, 129.1, 129.5, 131.9, 135.1, 137.4, 138.2, 141.3, 146.0, 151.3,
155.2, 160.9, 164.6; MS: m=z ¼ 516.09 (Mþ), 518.09 (Mþ þ 2), 520.09 (Mþ þ 4).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(2-methylphenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 19 (C27H21N6O2Cl). IR (KBr): 1245 (C-O-
1
=
=
C), 1650 (>C O), 1575 (-N N-), 1445 (C-N), 3020 & 2920 (C-H str); H NMR
(400 MHz, CDCl3): 2.3 (s, 3H, CH3), 3.9–4.0 (q, 3H, OCH3), 6.6 (s, 1H, C3-H),
7.0–7.7 (m, 12H, Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d:
15.2, 50.1, 56.0, 85.0, 111.6, 112.4, 113.9, 114.3, 114.4, 117.3, 121.1, 125.8, 128.1,
128.5, 128.7, 128.7, 129.1, 129.8, 129.8, 131.3, 135.1, 137.1, 139.1, 145.8, 146.1,
151.2, 160.7; MS: m=z ¼ 496.14 (Mþ), 498.14 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(3-methylphenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 20 (C27H21N6O2Cl). IR (KBr): 1265 (C-O-
1
=
=
C), 1665 (>C O), 1570(-N N-), 1430 (C-N), 3020 & 2910 (C-H str); H NMR
(400 MHz, CDCl3): 2.4 (s, 3H, CH3), 4.0–4.1 (q, 3H, OCH3), 6.6 (s, 1H, C3-H),
7.0–7.7 (m, 12H, Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d:
24.3, 50.1, 55.9, 85.0, 111.6, 112.4, 113.9, 114.3, 114.5, 117.3, 121.1, 125.8, 128.5,
128.6, 128.7, 129.1, 129.8, 129.8, 130.4, 131.0, 135.1, 138.4, 139.0, 145.8, 146.1,
151.2, 160.7; MS: m=z ¼ 496.14 (Mþ), 498.14 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(4-methylphenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 21 (C27H21N6O2Cl). IR (KBr): 1255 (C-O-
1
=
=
C), 1660 (>C O), 1565 (-N N-), 1435 (C-N), 3020 & 2920 (C-H str), H NMR
(400 MHz, CDCl3): 2.3 (s, 3H, CH3), 3.9–4.1 (q, 3H, OCH3), 6.7 (s, 1H, C3-H),
7.0–7.7 (m, 12H, Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d:
24.3, 50.1, 55.9, 85.0, 111.6, 112.4, 113.9, 114.3, 114.3, 117.3, 121.1, 125.7, 128.5,
128.7, 128.7, 129.1, 129.1, 129.8, 129.8, 131.2, 135.1, 138.4, 139.0, 145.8, 146.0,
151.1, 160.7; MS: m=z ¼ 496.14 (Mþ), 498.14 (Mþ þ 2).

1260
N. B. PATEL AND R. D. SHARMA
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(2-nitrophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 22 (C26H18N7O4Cl). IR (KBr): 1240 (C-O-
1
=
=
C), 1665 (>C O), 1575 (-N N-), 1430 (C-N), 3015 & 2915 (C-H str); H NMR
(400 MHz, CDCl3): 3.8–3.9 (q, 3H, OCH3), 6.7 (s, 1H, C3-H), 7.0–7.7 (m, 12H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 50.1, 55.9, 85.0,
111.6, 112.4, 113.9, 114.3, 114.4, 117.3, 121.1, 121.1, 124.0, 128.5, 129.7, 129.7,
129.8, 129.8, 131.1, 134.9, 135.1, 139.0, 145.8, 146.2, 148.0, 151.0, 160.7; MS: m=
z ¼ 527.11 (Mþ), 529.11 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(3-nitrophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 23 (C26H18N7O4Cl). IR (KBr): 1250 (C-O-
1
=
=
C), 1650 (>C O), 1560 (-N N-), 1425 (C-N), 3010 & 2910 (C-H str); H NMR
(400 MHz, CDCl3): 3.9–4.0 (q, 3H, OCH3), 6.6 (s, 1H, C3-H), 7.0–7.7 (m, 12H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 50.1, 55.9, 85.0,
111.6, 112.4, 113.9, 114.3, 114.3, 117.3, 121.1, 121.1, 124.0, 128.5, 129.6, 129.7,
129.8, 129.8, 131.0, 134.9, 135.1, 139.1, 145.8, 146.1, 148.0, 151.2, 160.7; MS: m=
z ¼ 527.11 (Mþ), 529.11 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(4-nitrophenylazo)-6-(1H-
1,2,4-triazol-1-yl)-pyridin-2(1H)-one 24 (C26H18N7O4Cl). IR (KBr): 1255 (C-O-
1
=
=
C), 1655 (>C O), 1570 (-N N-), 1430 (C-N), 3020 & 2920 (C-H str); H NMR
(400 MHz, CDCl3): 3.9–4.1 (q, 3H, OCH3), 6.6 (s, 1H, C3-H), 6.9–7.6 (m, 12H,
Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d: 50.1, 55.9, 85.0,
111.6, 112.4, 113.9, 114.3, 114.3, 117.3, 121.1, 121.1, 121.2, 128.5, 129.7, 129.7,
129.8, 129.8, 131.1, 134.8, 135.1, 139.0, 145.8, 146.0, 148.0, 151.1, 160.7; MS: m=
z ¼ 527.11 (Mþ), 529.11 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-5-(2-methoxyphenylazo)-
6-(1H-1,2,4-triazol-1-yl)-pyridin-2(1H)-one 25 (C27H21N6O3Cl). IR (KBr): 1260
=
=
& 1250 (C-O-C), 1660 (>C O), 1570 (-N N-), 1420 (C-N), 3015 & 2910 (C-H
str); 1H NMR (400 MHz, CDCl3): 3.9–4.0 (q, 6H, OCH3), 5.9 (s, 1H, C5-H),
7.0–7.7 (m, 12H, Ar-H), 8.1–8.2 (s, 2H, tr-H); 13C NMR (100 MHz, CDCl3) d:
55.9, 55.9, 85.0, 99.6, 114.3, 114.3, 114.4, 118.9, 119.7, 121.1, 121.1, 121.9, 124.5,
129.8, 129.8, 129.8, 129.9, 130.4, 134.2, 134.5, 139.1, 146.0, 146.5, 151.2, 159.1,
160.7, 160.7; MS: m=z ¼ 512.14 (Mþ), 514.14 (Mþ þ 2).
4-(4-Methoxyphenyl)-1-(3-chlorophenyl)-6-(1H-1,2,4-triazol-1-
yl)-3-[(1H-1,2,4-triazol-1-yl)methyl]-pyridin-2(1H)-one 26
A mixture of paraformaledhyde (0.3 g, 0.01 mol) and 1,2,4-triazole (0.69 g,
0.01 mol) was refluxed for 45 min in chlorobenzene (50 ml). Compound 3
(0.01 mol) was then added to the reaction mixture and refluxed for 18 h, and then
the reaction mass was subjected to steam distillation to remove chlorobenzene.
The solid product was filtered, washed, and crystallized from acetone.
=
IR (KBr): 1260 (C-O-C), 1650 (>C O), 1570 (-N N-), 1435 (C-N), 3010 &
=
1
2920 (C-H str); H NMR (400 MHz, CDCl3): 3.9–4.0 (q, 3H, OCH3), 4.4(s, 2H,
CH2-tr) 5.9 (s, 1H, C5-H), 7.0–7.7 (m, 8H, Ar-H), 8.0 (s, 2H, tr-H), 8.3 (s, 2H,
tr-H); 13C NMR (100 MHz, CDCl3) d: 49.8, 55.7, 70.4, 76.9, 84.1, 114.2, 119.7,

2-(1H)-PYRIDONES WITH ARYL DIAZO
1261
122.1, 123.8, 124.5, 124.9, 127.5, 130.6, 134.1, 134.5, 139.2, 146.5, 146.8, 151.3, 158.3,
159.9; MS: m=z ¼ 459.12 (Mþ), 461.12 (Mþ þ 2).
ACKNOWLEDGMENTS
The authors thank the head, Department of Chemistry, for laboratory facili-
ties. One of us (R. D. S.) is grateful to Veer Narmed South Gujarat University for
financial support and for FTIR spectra. We also thank Rajani Microcare Labora-
tory, Surat, for antimicrobial and antitubercular activities, CDRI Lucknow for
1
13
elemental analysis, and SAIF Chandigarh for H and C NMR spectral analysis.
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