Synthesis and antimicrobial activity of chromone-linked 2-pyridone fused with 1,2,4-triazoles, 1,2,4-triazines and 1,2,4-triazepines ring systems

Article abstract of DOI:10.1590/S0103-50532010000600010

Three series of novel fused nitrogen heterocyclic systems such as 1,2,4-triazolo[1,5-a] pyridines (5-7 and 9), pyrido[1,2-b][1,2,4]triazines (10, 11, 13 and 15), and pyrido[1,2-b][1,2,4]triazepines (17, 18, 20 and 22) linked with a chromone moiety were synthesized from the key intermediate 1,6-diamino-(6-chloro-4-oxo-4H-chromen-3-yl)-2-oxo-1,2-dihydropyridine-3, 5-dicarbonitrile (4) with some electrophilic reagents. The structures of the novel compounds were established by elemental analyses and spectral data. All the products were also screened in vitro for their antimicrobial activity. Compounds 7, 9 and 15 showed the highest activities when compared with the reference drugs.

Full text of DOI:10.1590/S0103-50532010000600010

J. Braz. Chem. Soc., Vol. 21, No. 6, 1007-1016, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused with
1,2,4-Triazoles, 1,2,4-Triazines and 1,2,4-Triazepines Ring Systems
Tarik El-Sayed Ali and Magdy Ahmed Ibrahim*
Department of Chemistry, Faculty of Education, Ain Shams University, Roxy 11711, Cairo, Egypt
Três novas séries de sistemas heterocíclicos nitrogênio fundidos como o 1,2,4-triazol[1,5-a]
piridinas (5-7 e 9), pirido[1,2-b][1,2,4]triazinas (10, 11, 13 e 15), e também pirido[1,2-b] [1,2,4]
triazepinas (17, 18, 20 e 22) ligadas a um fragmento cromona foram sintetizadas a partir do
intermediário-chave 1,6-diamino-(6-cloro-4-oxo-4H-chromen-3-il)-2-oxo-1,2-diidropiridina-3,5-
dicarbonitrila (4) com alguns reagentes eletrofílicos. As estruturas dos compostos inéditos foram
estabelecidas por análise elementar e dados espectrais. Todos os produtos foram testados quanto
à sua atividade antimicrobiana in vitro. Os compostos 7, 9 e 15 mostraram as maiores atividades
quando comparadas às drogas de referência.
Three series of novel fused nitrogen heterocyclic systems such as 1,2,4-triazolo[1,5-a] pyridines
(5-7 and 9), pyrido[1,2-b][1,2,4]triazines (10, 11, 13 and 15), and pyrido[1,2-b][1,2,4]triazepines
(17, 18, 20 and 22) linked with a chromone moiety were synthesized from the key intermediate
1,6-diamino-(6-chloro-4-oxo-4H-chromen-3-yl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile
(4) with some electrophilic reagents. The structures of the novel compounds were established
by elemental analyses and spectral data. All the products were also screened in vitro for their
antimicrobial activity. Compounds 7, 9 and 15 showed the highest activities when compared with
the reference drugs.
Keywords: chromone, o-diamine, triazolopyridone, pyridotriazine, pyridotriazepine,
antimicrobial activity
Introduction
biodynamic nitrogen heterocycles such as 1,2,4-triazoles,
1,2,4-triazines and 1,2,4-triazepines fused with 2-pyridone
ring containing a chromone moiety.
Thepharmacodynamicversatilityof4-oxo-4H-chromene
moiety has been documented not only in many of its
synthetic derivatives but also in several naturally occurring
flavones and khellins.1-3 These synthesized and isolated
derivatives were found to have a wide range of biological
properties including antiinflammatory,4 analgesic,5
antimicrobial,6-8 antitumor9 and anticancer.10 Pyridines are
an important class of heterocycles due to their practical
and synthetic applications.11 In particular, some 2-pyridone
derivatives possess diverse bioactivities such as analgesic,12
antiinflammatory13 and anticancer.14 On the other hand,
1,2,4-triazoles, 1,2,4-triazines and 1,2,4-triazepines have
been found to possess a wide spectrum of pharmacological,
medicinal and biological activities.15-20 As part of our
research work aiming to the synthesis of a variety of fused
heterocyclic systems for biological evaluation, we report
here efficient and convenient synthetic methods of different
Results and Discussion
1,6-Diamino-(6-chloro-4-oxo-4H-chromen-3-yl)-
2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4) was
prepared in good yield by refluxing alcoholic solution
of [6-chloro-4-oxo-4H-chromen-3-yl)methylene]
malononitrile (2) with cyanoacetohydrazide or N´-[(6-
chloro-4-oxo-4H-chromen-3-yl)-2-cyanoacetohydrazide
(3) with malononitrile in the presence of a catalytic amount
of piperidine (Scheme 1). The IR spectrum of compound
4 showed characteristic absorption bands at 3401, 3308
(2 NH2), 2259 (2 C≡N), 1681 (C=Opyridone) and 1641 cm-1
1
(C=Opyrone). Also, the H NMR spectrum of 4 exhibited
two characteristic singlet signals at d 4.61 (N–NH2) and
10.78 ppm (C–NH2). These results indicated the difference
in nucleophilicity between the two amino groups. Thus,
it is expected that the hydrazide b-nitrogen (N–NH2) is
*e-mail: magdy_ahmed1977@yahoo.com

1008
Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused
J. Braz. Chem. Soc.
Scheme 1. Synthetic pathways for the formation of compound 4.
more nucleophilic and will react more rapidly with the
electron deficient carbon than the second amino group
(C–NH2). Product 4 was assumed to be formed via an
initial addition of the active methylene of malononitrile to
the hydrazone linkage in 3 to yield a Michael adduct A.
This adduct dissociates into 2-cyanoacetohydrazide and
2, which then further react in the way described earlier
by El-Najar and co-workers21 to yield an intermediate
tricyanobutyrohydrazide B that cyclizes to intermediates
C then D. The intermediate D underwent dehydrogenation
to afford the isolated product 4 (Scheme 2).
The 1,6-diamino groups are ready-made nucleophilic
centers for the synthesis of fused nitrogen heterocyclic
rings.22 Thus, compound 4 is a useful intermediate for
the synthesis of new triazolopyridone, pyridotriazine
and pyridotriazepine derivatives. Heterocyclization of
compound 4 with ethyl formate and acetic anhydride
afforded the triazolo[1,5-a]pyridine derivatives 5 and 6,
respectively (Scheme 3). The IR and 1H NMR spectra of
the latter compounds confirmed the absence of the two
NH2 groups. Furthermore, their 1H NMR spectra showed
characteristic singlet signal at d 8.61 ppm for H–3 of
Scheme 2. The proposed mechanism for the formation of compound 4.

Vol. 21, No. 6, 2010
Ali and Ibrahim
1009
triazole moiety in compound 5 and two singlet signals
at d 2.75 and 2.91 ppm corresponding to the two methyl
groups in compound 6.
triazino[4,5-d][1,2,4]triazine derivative 11 upon fusion
with benzoic acid hydrazide (Scheme 4). The IR spectrum
of compound 11 exhibited characteristic absorption
bands at 3335, 3197 (OH, NH), 2265, 2221 (2 C≡N),
1672 (C=Opyridone) and 1633 cm-1 (C=Opyrone). Also, its
1H NMR spectrum displayed signals at d 1.91, 10.53
and 13.27 ppm corresponding to methyl, NH and OH
hydrogens, respectively. The absence of the triplet and
quartet signals corresponding to the ethoxycarbonyl
hydrogens of compound 10 supported the formation of
compound 11.
In continuation to our interest in the synthesis of
chromone derivatives containing nitrogen heterocyclic
systems,7,8,23 compound 4 was allowed to react with
some chromone derivatives. Thus, cyclocondensation of
4 with 6-chloro-3-formylchromone (1) in DMF under
reflux containing few drops of piperidine afforded the
1,2,3,5-tetrahydro[1,2,4] triazolo[1,5-a]pyridine derivative
7. Oxidation of the latter compound by ferric chloride
in boiling DMSO yielded 2,7-bis(6-chloro-4-oxo-4H-
chromen-3-yl)-5-oxo-1,5-dihydro-1,2,4-triazolo [1,5-a]
pyridine-6,8-dicarbonitrile (9). Compound 9 was also
obtained by refluxing 4 with 6-chloro-chromone-3-
carboxylic acid (8) in phosphorus oxychloride (Scheme 3).
The analytical and spectral data of 7 and 9 are in agreement
with the proposed structures. Thus, the 1H NMR spectrum
of 7 showed a triplet signal at d 6.99 ppm corresponding
to N–CH–N hydrogen of triazole moiety and a doublet
signal at d 10.51 ppm due to N2–H hydrogen of the triazole
moiety. These two hydrogens were absent in the 1H NMR
spectrum of compound 9 that confirmed the oxidation
process of its dihydroanalogue 7.
Next, we allowed compound 4 to react with
1,2-dielectrophilic reagents to develop a facile and
convenient route to polysubstituted pyrido[1,2-b][1,2,4]
triazine derivatives with an expected wide spectra of
biological activities.24 Thus, cyclocondensation of 4
with ethyl 2-chloro-3-oxobutanoate in DMF containing
a catalytic amount of piperidine under reflux produced
the pyrido[1,2-b][1,2,4]triazine-2-carboxylate derivative
10, which was transformed to the pyrido[1,2-b][1,2,4]
On the other hand, the interaction of 4 with
2,3-dichloroquinoxaline (12) and 3-chloro-7,8-diphenyl-
4H-1,2,4-triazino[4,3-b][1,2,4]triazine (14) in pyridine led
to the formation of the corresponding quinoxalino[2,3-e]
pyrido[1,2-b][1,2,4]triazine 13 and pyrido[1,2-b][1,2,4]
triazino[3’,2’:3,4]triazino[5,6-e][1,2,4]triazine 15,
1
respectively (Scheme 4). The H NMR spectrum of 13
showed four broad signals at d 10.72, 11.28, 11.94 and
12.21 ppm assignable to four NH hydrogens which
confirmed that the product 13 exists in two tautomeric forms
13A and 13B due to amino-imino tautomerism.
The study was extended to investigate the behavior
of 1,6-diaminopyridone derivative 4 towards some
1,3-dielectrophilic reagents which represents a new, simple
and efficient synthetic route to prepare pyrido[1,2-b]
[1,2,4]triazepine derivatives. Therefore, refluxing 4 with
acetylacetone and arylidene malononitrile 16 in DMF
containing few drops of piperidine as a basic catalyst
furnished the pyrido[1,2-b][1,2,4]triazepine derivatives 17
and 18, respectively (Scheme 5). The 1H NMR spectrum
of 17 showed a singlet signal at d 4.63 ppm due to CH2
hydrogens while compound 18 displayed broad signals at
Scheme 3. Synthetic pathway for the formation of 1,2,4-triazolo[1,5-a]pyridines.

1010
Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused
J. Braz. Chem. Soc.
d 8.89 and 10.67 ppm assigned to NH2 and NH hydrogens,
respectively.
Furthermore, we also investigated the reactivity of 4
towards enaminone and ketene N,S-acetal. Thus, reaction
of 4 with 4-(dimethylamino)but-3-en-2-one (19) in
glacial acetic acid afforded the 5,7-dihydropyrido[1,2-b]
[1,2,4]triazepine derivative 20 (Scheme 5). The structure
of the latter product was confirmed from its elemental
Scheme 4. Synthetic pathway for the formation of pyrido[1,2-b][1,2,4]triazines.
Scheme 5. Synthetic pathway for the formation of pyrido[1,2-b][1,2,4]triazepines.

Vol. 21, No. 6, 2010
Ali and Ibrahim
1011
analysis which agreed well with the molecular formula
C20H10ClN5O3. Also, its H NMR spectrum showed a
Antimicrobial activity
1
25
singlet signal at d 2.34 ppm corresponding to the methyl
hydrogens, besides a doublet signal at d 7.94 ppm assigned
to C7–H hydrogen of triazepine ring. The formation of
compound 20 was assumed to take place via an initial
Michael addition of the hydrazide b-nitrogen (N–NH2)
group in 4 to the activated double bond in enaminone
followed by cyclization via loss of both dimethylamine
and water molecules.24
Finally, treatment of 4 with ketene N,S-acetal derivative
21 in DMF under reflux containing few drops of piperidine
produced 2-amino-9-(6-chloro-4-oxo-4H-chromen-3-
yl)-8,10-dicyano-N-phenyl-4-(phenylamino)-7-oxo-5,7-
dihydropyrido[1,2-b][1,2,4]triazepine-3-carboxamide (22)
(Scheme 5). The formation of 22 was assumed to take
place via nucleophilic attack of (N-NH2) on compound
21 to remove methanethiol followed by cycloaddition of
the second amino group (C-NH2) on the nitrile group. The
IR spectrum of 22 showed absorption bands for NH2, NH
and C=Oamide groups at 3375-3325, 3152 and 1648 cm-1,
respectively, while its 1H NMR spectrum showed signals
at d 8.08, 9.91, 10.63 and 11.08 ppm assigned to the NH2
and three NH hydrogens, respectively.
The standardized disc agar diffusion method was
followed to determine the activity of the synthesized
compounds against the sensitive organisms Staphylococcus
aureus (ATCC 25923) and Streptococcus pyogenes (ATCC
19615) as Gram positive bacteria, Pseudomonas fluorescens
(S 97) and Pseudomonas phaseolicola (GSPB 2828) as
Gram negative bacteria and two species of fungi, namely
Fusarium oxysporum and Aspergillus fumigatus. The
antibiotic chloramphenicol was used as reference in the case
of Gram negative bacteria, while cephalothin was used in
the case of Gram positive bacteria and cycloheximide was
used as antifungal reference.
The compounds were dissolved in DMF which has
no inhibition activity to get concentration of 2 mg mL-1.
The test was performed on medium potato dextrose
agars (PDA) which contain infusion of 200 g potatoes,
6 g dextrose and 15 g agar.26 Uniform size filter paper
disks (3 disks per compound) were impregnated with
equal volume (10 µL) from the specific concentration
of dissolved tested compounds and carefully placed on
inoculated agar surface. After incubation for 36 h at 27 °C
in the case of bacteria and for 48 h at 24 °C in the case
Table 1. The antimicrobial activity of compounds 4-7, 9-11, 13, 15, 17, 18, 20 and 22
Diameter of the inhibition zone in mma,b (activity index)c
Compd. No.
Gram positive bacteria
S. pyogenes
Gram negative bacteria
Fungal strains
F. oxysporum
S. aureus
4 (0.14)
12 (0.43)
18 (0.64)
23 (0.82)
25 (0.89)
7 (0.25)
11 (0.39)
10 (0.36)
24 (0.86)
5 (0.18)
6 (0.21)
12 (0.43)
4 (0.14)
−
P. phaseolicola P. fluorescens
A. fumigatus
7 (0.22)
15 (0.48)
13 (0.43)
21 (0.68)
19 (0.61)
5 (0.16)
12 (0.39)
6 (0.19)
27 (0.87)
8 (0.25)
14 (0.45)
15 (0.48)
4 (0.13)
−
4
3 (0.10)
13 (0.43)
16 (0.53)
21 (0.70)
26 (0.87)
6 (0.20)
13 (0.43)
13 (0.43)
23 (0.77)
7 (0.23)
6 (0.20)
14 (0.47)
7 (0.23)
−
8 (0.32)
14 (0.56)
16 (0.64)
17 (0.68)
15 (0.60)
4 (0.16)
16 (0.64)
12 (0.48)
18 (0.72)
7 (0.28)
7 (0.28)
15 (0.60)
7 (0.28)
25
9 (0.30)
22 (0.73)
13 (0.43)
21 (0.70)
18 (0.60)
10 (0.33)
10 (0.33)
17 (0.57)
22 (0.73)
10 (0.33)
12 (0.40)
22 (0.73)
10 (0.33)
30
6 (0.21)
14 (0.50)
10 (0.36)
16 (0.57)
20 (0.71)
8 (0.28)
10 (0.36)
8 (0.28)
21 (0.75)
5 (0.18)
20 (0.71)
14 (0.50)
8 (0.28)
−
5
6
7
9
10
11
13
15
17
18
20
22
chloramphenicol
cephalothin
cycloheximide
28
30
−
−
−
−
−
−
−
−
28
31
b
aCalculated from 3 values; Identified depending on morphological and microscopical characteristics: Low activity = mean of zone diameter ≤ 0.33
of mean zone diameter of reference. Moderate activity = mean of zone diameter > 0.33 ≤ 0.66 of mean zone diameter of the reference compound.
High activity = mean of zone diameter ≥ 0.67 of mean zone diameter of the reference compound; cActivity index: inhibition zone of the sample /inhibition
zone of the reference compound.

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Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused
J. Braz. Chem. Soc.
of fungi, inhibition of the organisms was measured and
used to calculate mean of inhibition zones. Activity index
of all the synthesized compounds was also calculated
against the corresponding standard drug (Table 1). The
products showed various activities against all species of
microorganisms which suggest that the variations in the
structures affect on the growth of the microorganisms.
Thus, we can conclude from these results: i) The prepared
compounds showed a moderate to high antimicrobial
activity towards all species of bacteria and fungi
(Table 1); ii) It is known that compounds having oxygen
heterocycles and active hydrogen at nitrogen groups (NH)
can be preferable in the design of good bioregulators with
desirable prompt biological activity.Also, the chromon-3-yl
residue can simultaneously increase the activity and
decrease the toxicity of nitrogen heterocycles.27 Thus,
the building up of compounds containing more nitrogen
heterocycles on the 1,6-diamino-(6-chloro-4-oxo-
4H-chromen-3-yl)-2-oxo-1,2-dihydropyridine-3,5-
dicarbonitrile (4) may enhance the biological activities
in most of the products in comparison with compound
4; iii) Compounds which have 1,2,4-triazole ring fused
with 2-pyridone showed greater activity than that of
1,2,4-triazine and 1,2,4-triazepine; iv) Compounds 7 and
9 showed the highest antimicrobial activity. This high
effect may due to the presence of two chromone moieties
besides the triazolopyridone moiety. Also, compound 15
has the same effect which may be attributed to the presence
of polyfused bioactive 1,2,4-triazine systems.28 Therefore,
these compounds may be considered promising for the
development of new antimicrobial agents.
were performed at Microanalysis Unit in National
Research Center. Evaluation of antimicrobial activities
was carried out in the Faculty of Agriculture, Al-Azhar
University for Girls, Nasr-City, Cairo, Egypt. 6-Chloro-3-
formylchromone (1),29 [(6-chloro-4-oxo-4H-chromen-3-yl)
methylene] malononitrile (2),30 N'-[(6-chloro-4-oxo-4H-
chromen-3-yl)methylene]-2-cyanoacetohydrazide (3),31
6-chloro-chromone-3-carboxylic acid (8),32 3-chloro-
7,8-diphenyl-4H-[1,2,4]triazino[4,3-b][1,2,4] triazin-4-
one (14)33 and 2-cyano-3-(methylsulfanyl)-N-phenyl-3-
(phenylamino)prop-2-enamide (21)34 were prepared by
published methods in literature.
1,6-Diamino-(6-chloro-4-oxo-4H-chromen-3-yl)-2-oxo-
1,2-dihydropyridine-3,5-dicarbonitrile (4)
Method A
A mixture of [(6-chloro-4-oxo-4H-chromen-3-yl)
methylene]malononitrile (2) (1280 mg, 5 mmol) and
cyanoacetohydrazide (500 mg, 5 mmol), in absolute ethanol
(30 mL) containing few drops of piperidine, was refluxed
for 3 h. After cooling, the formed solid was filtered and
recrystallized from DMF to afford 4 as beige crystals, yield
74%, mp 288-289 °C.
Method B
A mixture of N'-[(6-chloro-4-oxo-4H-chromen-3-yl)
methylene]-2-cyanoaceto-hydrazide (3) (1450 mg, 5 mmol)
and malononitrile (330 mg, 5 mmol), in absolute ethanol
(30 mL) containing few drops of piperidine, was refluxed
for 3 h. After cooling, the formed solid was filtered and
crystallized from DMF to afford 4 as beige crystals, yield
77%, mp 288-290 °C. IR (KBr) nmax/cm-1: 3401, 3308
(2 NH2), 3058 (C−Harom), 2259 (2 C≡N), 1681 (C=Opyridone),
Conclusion
1
We have successfully synthesized three series of
novel fused nitrogen heterocyclic systems such as
1,2,4-triazolo[1,5-a]pyridines, pyrido[1,2-b][1,2,4]
triazines and pyrido[1,2-b][1,2,4]triazepines linked with
a chromone moiety. The antimicrobial activities of the
prepared compounds showed that polyheterocyclic systems
7, 9 and 15 have good inhibitory effects when compared
with the starting material.
1641 (C=Opyrone), 1468 (NH2 def.). H NMR (DMSO-d6)
d 4.61 (s, 2H, N−NH2), 7.13 (d, 1H, J 8 Hz, H-8), 7.54 (d,
1H, J 8 Hz, H-7), 8.53 (s, 1H, H-5), 9.48 (s, 1H, H-2), 10.78
(s, 2H, C−NH2). Anal. Calc. for C16H8ClN5O3 (353.71):
C, 54.33; H, 2.28; N, 19.80; Cl, 10.02. Found: C, 54.01;
H, 2.02; N, 19.54; Cl, 9.69%.
7-(6-Chloro-4-oxo-4H-chromen-3-yl)-5-oxo-1,5-
dihydro[1,2,4]triazolo[1,5-a]pyridine-6,8-dicarbonitrile
(5)
Experimental
A mixture of compound 4 (1710 mg, 5 mmol) and ethyl
formate (370 mg, 5 mmol) in dry pyridine (30 mL) was
refluxed for 10 h. After cooling the reaction mixture was
poured onto ice and neutralized with concentrated HCl.
The formed solid was filtered, washed several times with
water and crystallized from DMF/H2O to give 5 as brown
crystals, yield 68%, mp 274-276 °C. IR (KBr) nmax/cm-1:
Melting points were determined on a digital Stuart
SMP3 apparatus. Infrared spectra were measured on Perkin-
Elmer 293 spectrophotometer using KBr disks. 1H NMR
spectra were measured on Gemini-200 spectrometer
(200 MHz), using DMSO-d6 as solvent and TMS (d in
ppm) as an internal standard. Elemental microanalyses

Vol. 21, No. 6, 2010
Ali and Ibrahim
1013
3261 (NH), 3037 (C−Harom), 2261 (2 C≡ N), 1683
(C=Opyridone), 1638 (C=Opyrone).1H NMR (DMSO-d6) d 7.10
(d, 1H, J 8.2 Hz, H-8), 7.55 (d, 1H, J 8.2 Hz, H-7), 8.53
(s, 1H, H-5), 8.61 (s, 1H, H-3triazole), 9.50 (s, 1H, H-2),
10.74 (br, 1H, NH).Anal. Calc. for C17H6ClN5O3 (363.71):
C, 56.14; H, 1.66; N, 19.26; Cl, 9.75. Found: C, 55.78;
H, 1.52; N, 18.89; Cl, 9.41%.
DMF/ethanol to afford 9 as pale brown crystals, yield
88%; mp > 300°C.
Method B
A mixture of compound 7 (1360 mg, 5 mmol) and ferric
chloride (2500 mg) in DMSO (25 mL) was refluxed for 4 h.
After cooling, the reaction mixture was poured onto 10%
aqueous sodium carbonate solution (75 mL) and stirred for
1 h at room temperature. The formed solid was filtered and
crystallized from DMF/ethanol to afford 9 as pale brown
crystals, yield 82%, mp > 300°C. IR (KBr) nmax/cm-1: 3402
(NH), 3059 (C−Harom), 2258 (2 C≡N), 1682 (C=Opyridone),
1-Acetyl-7-(6-chloro-4-oxo-4H-chromen-3-yl)-2-methyl-
5-oxo-1,5-dihydro-1,2,4-triazolo [1,5-a]pyridine-6,8-
dicarbonitrile (6)
A solution of compound 4 (1710 mg, 5 mmol) in acetic
anhydride (10 mL) was refluxed for 6 h. The excess solvent
was removed under vacuum to give a solid which was
crystallized from ethanol to afford 6 as brown crystals, yield
47%, mp 297-299 °C. IR (KBr) nmax/cm-1: 3073 (C−Harom),
2926 (C−Haliph), 2239 (2 C≡N), 1722 (C=Oacetyl), 1675
(C=Opyridone), 1622 (C=Opyrone). 1H NMR (DMSO-d6) d 2.75
(s, 3H, CH3), 2.91 (s, 3H, CH3), 7.07-7.97 (m, 2H, H-8
and H-7), 8.66 (s, 1H, H-5), 9.51 (s, 1H, H-2). Anal. Calc.
for C20H10ClN5O4 (419.77): C, 57.22; H, 2.40; N, 16.68;
Cl, 8.44. Found: C, 56.94; H, 2.12; N, 16.32; Cl, 8.07%.
1
1641 (2 C=Opyrone), 1598 (C=N). H NMR (DMSO-d6)
d 7.07-7.79 (m, 4H, H-8, H-8’, H-7 and H-7’), 8.35 (s, 1H,
H-5), 8.54 (s, 1H, H-5’), 8.68 (s, 1H, H-2), 9.51 (s, 1H,
H-2’), 11.64 (br, 1H, NH). Anal. Calc. for C26H9Cl2N5O5
(542.28): C, 57.59; H, 1.67; N, 12.91; Cl, 13.07. Found:
C, 57.22; H, 1.34; N, 12.64; Cl, 12.76%.
Ethyl 8-(6-chloro-4-oxo-4H-chromen-3-yl)-7,9-dicyano-
3-methyl-6-oxo-1,6-dihydro-4H-pyrido[1,2-b][1,2,4]
triazine-2-carboxylate (10)
A mixture of compound 4 (1710 mg, 5 mmol) and
ethyl 2-chloro-3-oxobutanoate (820 mg, 5 mmol), in DMF
(30 mL) containing few drops of piperidine, was refluxed
for 8 h. After cooling, the reaction mixture was onto ice-
water. The formed solid was filtered and crystallized from
AcOH/H2O to afford 10 as brown crystals, yield 69%, mp
188-190 °C. IR (KBr) nmax/cm-1: 3394, 3199 (2 NH), 3044
(C−Harom), 2978, 2925 (C−Haliph), 2260, 2198 (2 C≡N),
1734 (C=Oester), 1683 (C=Opyridone), 1635 (C=Opyrone), 1103
2,7-Bis(6-chloro-4-oxo-4H-chromen-3-yl)-5-oxo-
1,2,3,5-tetrahydro[1,2,4]triazolo[1,5-a] pyridine-6,8-
dicarbonitrile (7)
A mixture of compound 4 (1710 mg, 5 mmol) and
6-chloro-3-formylchromone (1) (1040 mg, 5 mmol), in
DMF (30 mL) containing few drops of piperidine, was
refluxed for 5 h. After cooling, the reaction mixture
was poured onto ice. The formed solid was filtered and
crystallized from DMF/ethanol to afford 7 as yellow
crystals, yield 93%, mp > 300 °C. IR (KBr) nmax/cm-1:
3395, 3186 (2 NH), 3075 (C−Harom), 2928 (C−Haliph), 2263
(2 C≡N), 1680 (C=Opyridone), 1632 (2 C=Opyrone). 1H NMR
(DMSO-d6) d 6.99 (t, 1H, N−CH−Ntriazole), 7.37-7.96 (m,
4H, H-8, H-8’, H-7 and H-7’), 8.35 (s, 1H, H-5), 8.53 (s,
1H, H-5`), 8.78 (s, 1H, H-2), 9.47 (s, 1H, H-2`), 10.51 (d,
1H, NH), 12.72 (br, 1H, NH).Anal. Calc. for C26H11Cl2N5O5
(544.30): C, 57.37; H, 2.04; N, 12.87; Cl, 13.02. Found:
C, 57.02; H, 1.75; N, 12.58; Cl, 12.71%.
1
(C−O−C). H NMR (DMSO-d6) d 1.24 (t, 3H, J 7.2 Hz,
OCH2CH3), 2.23 (s, 3H, CH3), 3.77 (br, 2H, OCH2CH3),
7.03-7.93 (m, 2H, H-8 and H-7), 8.53 (s, 1H, H-5), 9.51
(s, 1H, H-2), 10.64 (s, 1H, NH), 11.02 (br, 1H, NH).
Anal. Calc. for C22H14ClN5O5 (463.83): C, 56.97; H, 3.04;
N, 15.10; Cl, 7.64. Found: C, 56.69; H, 2.79; N, 14.78;
Cl, 7.28%.
1-Phenyl-10-(6-chloro-4-oxo-4H-chromen-3-yl)-4-
hydroxy-5-methyl-8-oxo-6H,8H-pyrido [1,2-b][1,2,4]
triazino[4,5-d][1,2,4]triazine-9,11-dicarbonitrile (11)
A mixture of compound 10 (2310 mg, 5 mmol) and
benzoic acid hydrazide (680 mg, 5 mmol), containing few
drops of triethylamine, was fused for 15 min at 190-200 °C.
The reaction mixture was cooled at room temperature and
treated with ethanol (5 mL). The formed solid was filtered
and crystallized from ethanol to afford 11 as brown crystals,
yield 44%, mp 262-264 °C. IR (KBr) nmax/cm-1: 3335 (br,
OH), 3197 (NH), 3050 (C−Harom), 2930 (C−Haliph), 2265,
2221 (2 C≡N), 1672 (C=Opyridone), 1633 (C=Opyrone), 1601
2,7-Bis(6-chloro-4-oxo-4H-chromen-3-yl)-5-oxo-1,5-
dihydro[1,2,4]triazolo[1,5-a]pyridine-6,8-dicarbonitrile(9)
Method A
A mixture of compound 4 (1710 mg, 5 mmol) and
6-chloro-chromone-3-carboxylic acid (8) (1070 mg,
5 mmol) in POCl3 (10 mL) was refluxed on water bath for
3 h. After cooling, the reaction mixture was poured onto
ice. The formed solid was filtered and crystallized from

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J. Braz. Chem. Soc.
(C=N). 1H NMR (DMSO-d6) d 1.91 (br, 3H, CH3), 7.05-7.95
(m, 7H, H-8, H-7 and Ph-H), 8.52 (s, 1H, H-5), 9.50 (s, 1H,
H-2), 10.53 (s, 1H, NH), 13.27 (br, 1H, OH). Anal. Calc.
for C27H14ClN7O4 (535.89): C, 60.51; H, 2.63; N, 18.30;
Cl, 6.61. Found: C, 60.23; H, 2.41; N, 17.98; Cl, 6.29%.
as brown crystals, yield 59%, mp 182-184 °C. IR (KBr)
n
max/cm-1: 3042 (C−Harom), 2977 (C−Haliph), 2261, 2219
(2 C≡N), 1683 (C=Opyridone), 1637 (C=Opyrone), 1600 (C=N).
1H NMR (DMSO-d6) d 2.94 (s, 3H, CH3), 3.16 (s, 3H, CH3),
4.63 (br, 2H, CH2), 6.90-7.45 (m, 2H, H-8 and H-7), 8.51 (s,
1H, H-5), 8.96 (s, 1H, H-2). Anal. Calc for C21H12ClN5O3
(417.80): C, 60.37; H, 2.89; N, 16.76; Cl, 8.48. Found:
C, 60.03; H, 2.57; N, 16.43; Cl, 8.19%.
11-(6-Chloro-4-oxo-4H-chromen-3-yl)-9-oxo-9,13-
dihydro-7H-quinoxalino[2,3-e]pyrido [1,2-b][1,2,4]
triazine-10,12-dicarbonitrile (13)
A mixture of compound 4 (1710 mg, 5 mmol) and
2,3-dichloroquinoxaline (12) (1000 mg, 5 mmol) in dry
pyridine (30 mL) was refluxed for 4 h. After cooling, the
reaction mixture was poured onto ice-water and neutralized
with diluted HCl. The formed solid was filtered and
crystallized from DMF/H2O to afford 13 as pale brown
crystals, yield 45%, mp > 300 °C. IR (KBr) nmax/cm-1:
3394, (br, NH), 3101 (NH), 3040 (C−Harom), 2241
(2 C≡N), 1675 (C=Opyridone), 1619 (C=Opyrone), 1556 (C=N).
1H NMR (DMSO-d6) d 7.01−8.07 (m, 6H, Ar-H), 8.68 (s,
1H, H-5), 9.53 (s, 1H, H-2), 10.72 (br, 1H, NHtriazine), 11.28
(br, 1H, NHquinaoxaline), 11.94 (br, 1H, NHtriazine), 12.21 (br,
1H, NHquinaoxaline). Anal. Calc. for C24H10ClN7O3 (479.83):
C, 60.07; H, 2.10; N, 20.43; Cl, 7.38. Found: C, 59.69;
H, 1.86; N, 20.07; Cl, 7.02%.
2-Amino-9-(6-chloro-4-oxo-4H-chromen-3-yl)-4-(4-
chlorophenyl)-7-oxo-dihydro-pyrido [1,2-b][1,2,4]
triazepine-3,8,10-tricarbonitrile (18)
A mixture of compound 4 (1710 mg, 5 mmol) and
(4-chlorobenzylidene) malononitrile (16) (940 mg,
5 mmol), in DMF (30 mL) containing a few drops of
piperidine, was refluxed for 10 h. After cooling, the reaction
mixture was poured onto ice-water. The formed solid was
filtered and crystallized from DMF to afford 18 as red
crystals, yield 39%, mp > 300 °C. IR (KBr) nmax/cm-1: 3276,
3199 (NH2, NH), 3070 (C−Harom), 2276 (2 C≡N), 2216
(C≡N), 1676 (C=Opyridone), 1619 (C=Opyrone), 1592 (C=N),
1466 (NH2 def). 1H NMR (DMSO-d6) d 7.10-8.19 (m, 6H,
Ar-H), 8.61 (s, 1H, H-5), 8.89 (br, 2H, NH2), 9.54 (s, 1H,
H-2), 10.67 (br, 1H, NH). Anal. Calc. for C26H11Cl2N7O3
(540.31): C, 57.80; H, 2.05; N, 18.15; Cl, 13.12. Found:
C, 57.52; H, 1.78; N, 17.77; Cl, 12.94%.
11-(6-Chloro-4-oxo-4H-chromen-3-yl)-9-oxo-2,3-
diphenyl-7H-pyrido[1,2-b][1,2,4] triazino[3`,2`:3,4]
triazino[5,6-e][1,2,4]triazine-10,12-dicarbonitrile (15)
A mixture of compound 4 (1710 mg, 5 mmol) and
3-chloro-7,8-diphenyl-4H-[1,2,4]triazino[4,3-b][1,2,4]
triazin-4-one (14) (1720 mg, 5 mmol) in dry pyridine
(30 mL) was refluxed for 12 h. After cooling, the reaction
mixture was poured onto ice-water, and neutralized with
diluted HCl. The formed solid was filtered and crystallized
from acetic acid to afford 15 as brown crystals, yield
49%, mp 225−227 °C. IR (KBr) nmax/cm-1: 3200 (br, NH),
3064 (C−Harom), 2224 (2 C≡N), 1675 (C=Opyridone), 1636
(C=Opyrone), 1600 (C=N). 1H NMR (DMSO-d6) d 7.14−8.37
(m, 12H,Ar-H), 8.52 (s, 1H, H-5), 9.46 (s, 1H, H-2), 10.82
(s, 1H, NH). Anal. Calc. for C33H15ClN10O3 (634.99):
C, 62.42; H, 2.38; N, 22.06; Cl, 5.58. Found: C, 62.16;
H, 2.07; N, 21.78; Cl, 5.19%.
9-(6-Chloro-4-oxo-4H-chromen-3-yl)-2-methyl-7-oxo-5,7-
dihydropyrido[1,2-b][1,2,4] triazepine-8,10-dicarbonitrile
(20)
A mixture of compound 4 (1710 mg, 5 mmol) and
4-(dimethylamino)but-3-en-2-one (19) (570 mg, 5 mmol)
in glacial acetic acid (30 mL) was refluxed for 10 h. After
cooling, the reaction mixture was poured onto ice-water.
The formed solid was filtered and crystallized from DMF/
ethanol to afford 20 as pale brown crystals, yield 96%,
mp 200-202 °C. IR (KBr) nmax/cm-1: 3394 (NH), 3039
(C−Harom), 2925 (C−Haliph), 2260 (2 C≡N), 1683 (C=Opyridone),
1625 (C=Opyrone), 1597 (C=N). 1H NMR (DMSO-d6) d 2.34
(s, 3H, CH3), 6.91-7.42 (m, 2H, H-8 and C6-Htriazepine), 7.49
(d, 1H, J 7.8 Hz, H-7), 7.94 (d, 1H, J 8 Hz, C7-Htriazepine),
8.52 (s, 1H, H-5), 9.46 (s, 1H, H-2), 10.67 (s, 1H, NH).
Anal. Calc. for C20H10ClN5O3 (403.77): C, 59.49; H, 2.50;
N, 17.34; Cl, 8.78. Found: C, 59.13; H, 2.37; N, 16.97;
Cl, 8.43%.
9-(6-Chloro-4-oxo-4H-chromen-3-yl)-2,4-dimethyl-7-
oxo-3,7-dihydropyrido[1,2-b][1,2,4] triazepine-8,10-
dicarbonitrile (17)
A mixture of compound 4 (1710 mg, 5 mmol) and
acetylacetone(500mg, 5mmol), inDMF(30mL)containing
few drops of piperidine, was refluxed for 10 h. After cooling,
the reaction mixture was poured onto ice-water. The formed
solid was filtered and crystallized from ethanol to afford 17
2-Amino-9-(6-chloro-4-oxo-4H-chromen-3-yl)-
8,10-dicyano-N-phenyl-4-(phenylamino)-7-oxo-5,7-
dihydropyrido[1,2-b][1,2,4]triazepine-3-carboxamide (22)
A mixture of compound 4 (1710 mg, 5 mmol) and
2-cyano-3-(methylsulfanyl)-N-phenyl-3-(phenylamino)

Vol. 21, No. 6, 2010
Ali and Ibrahim
1015
prop-2-enamide (21) (1550 mg, 5 mmol), in DMF (30 mL)
containing few drops of piperidine, was refluxed for 10 h.
After cooling, the reaction mixture was poured onto ice-
water. The formed solid was filtered and crystallized from
DMF/ethanol to afford 22 as pale brown crystals, yield
61%, mp 263-265 °C. IR (KBr) nmax/cm-1: 3375, 3325,
3152 (NH2, 3NH), 3071 (C−Harom), 2221 (2 C≡N), 1669
(C=Opyridone), 1648 (C=Oamide), 1630 (C=Opyrone), 1600
(C=N). 1H NMR (DMSO-d6) d 6.94-7.68 (m, 12H, Ar-H),
8.08 (br, 2H, NH2), 8.66 (s, 1H, H-5), 9.21 (s, 1H, H-2),
9.91 (s, 1H, NH), 10.63 (s, 1H, NH), 11.08 (br, 1H, NH).
Anal. Calc. for C32H19ClN8O4 (614.99): C, 62.49; H, 3.11;
N, 18.22; Cl, 5.76. Found: C, 62.09; H, 2.78; N, 17.81;
Cl, 5.43%.
R.; Spengler, G.; Ocsovszki, I.; Kawase, M.; Motohashi, N.;
Shirataki, Y.; Shah, A.; Molnar, J.; In Vivo 2006, 20, 645;
(CA 2007, 146: 287872); Boumendjel,A.; Nicolle, E.; Moraux,
T.; Gerby, B.; Blanc, M.; Ronot, X.; Boutonnat, J.; J. Med.
Chem. 2005, 48, 7275.
11. Collins, I.; Castro, J. L.; Tetrahedron Lett. 1999, 40, 4069;
Aberg, V.; Sellstedt, M.; Hedenstrom, M.; Pinkner, J. S.;
Hultgren, S. J.; Almqvist, F.; Bioorg. Med. Chem. 2006, 14,
7563.
12. Ozturk, G.; Erol, D. D.;Aytemir, M. D.; Uzbay, T.; Eur. J. Med.
Chem. 2002, 37, 829.
13. Amr, A. E.; Abdulla, M. M.; Bioorg. Med. Chem. 2006, 14,
4341.
14. Amr, A. E.; Mohamed, A. M.; Mohamed, S. F.; Abdel-Hafez,
N. A.; Hammam, A. E.; Bioorg. Med. Chem. 2006, 14, 5481;
Du, W. Tetrahedron 2003, 59, 8649; Cocco, M. T.; Congiu, C.;
Onnis V.; Eur. J. Med. Chem. 2000, 35, 545.
Supplementary Information
Supplementary data are available free of charge at
http://jbcs.sbq.org.br, as pdf file.
15. Ünver, Y.; Düğdü, E.; Sancak, K.; Er, M.; Karaoğlu, Ş.; Turk.
J. Chem. 2008, 32, 441; Özdemir, A.; Turan-Zitouni, G.;
Kaplancikli, Z. A.; Chevallet, P.; J. Enzyme Inhib. Med. Chem.
2007, 22, 511.
References
16. Vivet-Boudou, V.; Paillart, J. C.; Burger, A.; Marquet, R.;
Nucleosides, Nucleotides Nucleic Acids 2007, 26, 743;
Kiselyov,A. S.; Piatnitski, E.; Milligan, D.; Ouyang, X.; Chem.
Biol. Drug Des. 2007, 69, 331.
1. Djerngou, P. C.; Gatsing, D.; Tehuendem, M.; Ngadjui, B. T.;
Tane, P.; Ahmed, A. A.; Gamal-Eldeen, A. M.; Adoga, G. I.;
Hirata, T.; Mabry, T.; J. Nat. Prod. Commun. 2006, 1, 961.
2. Peng, J. Y.; Dong, F. Q.; Liu, K. X.; Xu, Y. W.; Qi, Y.; Xu, Q.
W.; Xu, L. N.; J. Asian Nat. Prod. Res. 2008, 10, 169.
3. Shi, Y. Q.; Fukai, T.; Sakagami, H.; Chang, W.-J.;Yang, P.-Q.;
Wang, F.-P.; Nomura, T.; J. Nat. Prod. 2001, 64, 181.
4. Sharma,V. P.; Asian J. Chem. 2004, 16, 1966. (CA 142: 298061);
Sharma, V. P.; Indian J. Heterocycl. Chem. 2004, 14, 35.
(CA 142: 373785).
17. Kumar, J.; Prabhakaran, J.; Majo, V.; Milak, M.; Hsiung, S.
C.; Tamir, H.; Simpson, N.; Heertum, R.; Mann, J.; Parsey, R.;
Eur. J. Nucl. Med. Mol. Imaging 2007, 34, 1050; El-Mariah, F;
Hosny, M; Deeb, A.; Phosphorus, Sulfur Silicon Relat. Elem.
2006, 181, 2505.
18. Mansour, A.; Eid, M. M.; Khalil, N. S. A. M.; Nucleosides,
Nucleotides Nucleic Acids 2003, 22, 1805; Mansour, A.; Eid,
M. M.; Khalil, N. S. A. M.; Nucleosides, Nucleotides Nucleic
Acids 2003, 22, 21.
5. Ghate, M.; Kusanur, R.A.; Kulkarni, M.V.; Eur. J. Med. Chem.
2005, 40, 882.
6. Nandgaonkar, R. G.; Ingle,V. N.; Asian J. Chem. 2005, 17, 2016.
(CA 144: 311814); Joshi, N. S.; Shaikh, A. A.; Deshpande, A.
P.; Karale, B. K.; Bhirud, S. B.; Gill, C. H.; Indian J. Chem.
2005, 44B, 422.(CA 144: 192164).
19. Reayi, A.; Hosmane, R. S.; J. Med. Chem. 2004, 47, 1044;
Reayi, A.; Hosmane, R. S.; Nucleosides, Nucleotides Nucleic
Acids 2004, 23, 263.
20. Ali, T. E.; Eur. J. Med. Chem. 2009, 44, 4385; Lamsabhi, M.;
Esseffar, M.; Bouab, W.; El Messaoudi, T.; El Messaoudi, M.;
Abboud, J. L. M.; Acami, M.; Yanez, M.; J. Phys. Chem. A
2002, 106, 7383.
7. Siddiqui, Z. N.; Khuwaja, G.; Asad, M.; Heterocycl. Commun.
2006, 12, 443; Ali, T. E.; Abdel-Aziz, S. A.; El-Shaaer, H. M.;
Hanafy, F. I.; El-Fauomy, A. Z.; Phosphorus, Sulfur Silicon
Relat. Elem. 2008, 183, 2139; Ibrahim M. A.; El-Mahdy K.
M.; Phosphorus, Sulfur Silicon Relat. Elem. 2009, 184, 2945.
8. Ali, T. E.; Phosphorus, Sulfur Silicon Relat. Elem. 2007, 182,
1717; Ali, T. E.; Abdel-Aziz, S. A.; El-Shaaer, H. M.; Hanafy
F. I.; El-Fauomy, A. Z.; Turk. J. Chem. 2008, 32, 365; Ali, T.
E.; Halacheva, S. S.; Heteroat. Chem. 2009, 20, 117.
9. Nawrot-Modranka, J.; Nawrot, E.; Graczyk, J.; Eur. J. Med.
Chem. 2006, 41, 1301.
21. Al-Najjar, A. A.; Amer, S. A.; Raid, M.; Elghamry, I.; Elnagdi,
M. H.; J. Chem. Res. 1996, 296.
22. Ibrahim, M. A.; Abdel-Rahman, R. M.; Abdel-Halim, A.
M.; Ibrahim, S. S.; Allimony, H. A.; Arkivoc 2008, 202;
Ibrahim, M. A.; Abdel-Rahman, R. M.; Abdel-Halim, A. M.;
Ibrahim, S. S.; Allimony, H. A.; J. Braz. Chem. Soc. 2009,
20, 1275.
23. Ali, T. E.; Abdel-Monem, W. R.; Phosphorus, Sulfur Silicon
Relat. Elem. 2008, 183, 2161.
10. Ishar, M. P. S.; Singh, G.; Singh, S.; Sreenivasan, K. K.; Singh,
G.; Bioorg. Med. Chem. Lett. 2006, 16, 1366; Barath, Z.; Radics,
24. Ibrahim, N. S.; Chem. Ind. 1989, 654.

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Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused
J. Braz. Chem. Soc.
25. Rahman, A. U.; Choudhary, M. I.; Thomsen, W. J.; Bioassay
30. Hangarge, R. V.; Sonwane, S. A., Jarikote, D. V.; Shingare, M.
S.; Green Chem. 2001, 3, 310.
Techniques for Drug Development, Harwood Academic
Publishers: The Netherlands, 2001.
31. El-Shaaer, H. M.; Foltínová, P.; Lácová, M.; Chovancová, J.;
Stankovičová, H.; Il Farmaco 1998, 53, 224.
32. Machida, Y.; Nomoto, S.; Negi, S.; Jkuta, H.; Saito, I.; Synth.
Commun. 1980, 10, 889.
26. Khan, K. M.; Saify, Z. S.; Zeesha, A. K.; Ahmed, M.; Saeed,
M; Schick, M.; Kohlbau, H. J.; Voelter, W.; Arzneim. Forsch.
2000, 50, 915.
27. Tuskaev, V. A.; Oganesyan, E. T.; Mutsueva, S. K.; Pharma.
Chem. J. 2002, 36, 309.
33. Abdel-Rahman, R. M.; Seada, M.; Fawzy, M.; El-Baz, I.; Asian
J. Chem. 1993, 5, 176.
28. Abdel-Rahman, R. M.; Pharmazie 2001, 56, 18; El-Gendy, Z.;
Morsy, J. M.; Allimony, H. A.; Abdel-Monem, W. R.; Abdel-
Rahman, R. M.; Pharmazie 2001, 56, 376.
34. Kurz, T.; Widyan, K.; Elgemeie, G. H.; Phosphorus, Sulfur
Silicon Relat. Elem. 2006, 181, 299.
29. Nohara, A.; Umetani, T.; Sann, O. Y.; Tetrahedron 1974, 30,
3553.
Received: March 24, 2009
Web Release Date: March 4, 2010

J. Braz. Chem. Soc., Vol. 21, No. 6, S1-S8, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused with
1,2,4-Triazoles, 1,2,4-Triazines and 1,2,4-Triazepines Ring Systems
Tarik El-Sayed Ali and Magdy Ahmed Ibrahim*
Department of Chemistry, Faculty of Education, Ain Shams University, Roxy 11711, Cairo, Egypt
Figure S1. IR spectrum of compound 4.
*e-mail: magdy_ahmed1977@yahoo.com

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Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused
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Figure S2. 1H NMR spectrum of compound 4.
Figure S3. IR spectrum of compound 5.

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Figure S4. 1H NMR spectrum of compound 5.
Figure S5. IR spectrum of compound 7.

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Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused
J. Braz. Chem. Soc.
Figure S6. 1H NMRR spectrum of compound 7.
Figure S7. IR spectrum of compound 11.

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Figure S8. 1H NMR spectrum of compound 11.
Figure S9. IR spectrum of compound 13.

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Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused
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Figure S10. 1H NMR spectrum of compound 13.
Figure S11. IR spectrum of compound 15.

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Figure S12. 1H NMR spectrum of compound 15.
Figure S13. IR spectrum of compound 20.

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Synthesis and Antimicrobial Activity of Chromone-linked 2-Pyridone Fused
J. Braz. Chem. Soc.
Figure S14. 1H NMR spectrum of compound 20.