Synthesis and antimicrobial activity of some new heterocyclic schiff bases derived from 2-Amino-3-formylchromone

Article abstract of DOI:10.1080/10426500802625594

Some new hydrazone derivatives 3a-e have been obtained from 2-amino-3-formylchromone (1). Heterocyclization of thiocarbohydrazone derivative 3e via reaction with some electrophilic reagents afforded 1,2,4-triazoles 6-8 and 1,2,4-triazines 9-13. Condensati

Full text of DOI:10.1080/10426500802625594

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Phosphorus, Sulfur, and Silicon
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Synthesis and Antimicrobial
Activity of Some New
Heterocyclic Schiff Bases
Derived from 2-Amino-3-
formylchromone
Magdy A. Ibrahim a & Kamelia M. El-Mahdy a
a Department of Chemistry, Faculty of Education,
Ain Shams University, Cairo, Egypt
Published online: 03 Nov 2009.
To cite this article: Magdy A. Ibrahim & Kamelia M. El-Mahdy (2009) Synthesis and
Antimicrobial Activity of Some New Heterocyclic Schiff Bases Derived from 2-Amino-3-
formylchromone, Phosphorus, Sulfur, and Silicon and the Related Elements, 184:11,
2945-2958, DOI: 10.1080/10426500802625594
To link to this article: http://dx.doi.org/10.1080/10426500802625594
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Phosphorus, Sulfur, and Silicon, 184:2945–2958, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802625594
Synthesis and Antimicrobial Activity of Some New
Heterocyclic Schiff Bases Derived from
2-Amino-3-formylchromone
Magdy A. Ibrahim and Kamelia M. El-Mahdy
Department of Chemistry, Faculty of Education, Ain Shams University,
Cairo, Egypt
Some new hydrazone derivatives 3a–e have been obtained from 2-amino-3-
formylchromone (1). Heterocyclization of thiocarbohydrazone derivative 3e via
reaction with some electrophilic reagents afforded 1,2,4-triazoles 6–8 and 1,2,4-
triazines 9–13. Condensation reactions of aldehyde 1 with o-aminoaldehydes
and/or ketones afforded some new isolated and condensed heterocyclic systems
17, 19, and 20. The newly synthesized compounds were screened for their antimi-
crobial activity.
Keywords Antimicrobial activity; chromone; Schiff bases; 1,2,4-triazines; 1,2,4-
triazoles
INTRODUCTION
Chromone derivatives have received great attention for their appli-
cations. These compounds exhibit a wide spectrum of biological ac-
tivities including antimicrobial,1,2 antibacterial,3,4 antitumor,5 antifun-
gal,6–8 anti-allergic,9 antiviral,10 anti-inflammatory,11 and anticancer
activities.12 Structural modification of the chromone by the introduc-
tion of heterocyclic substituents at 3-position has attracted consider-
able attention.13,14 On the other hand, 1,2,4-triazole derivatives are
found to be associated with various biological activities.15–18 Moreover,
various 1,2,4-triazine derivatives are known to possess an array of
medicinal activities.19 In view of these observations, the present work
aimed to synthesize some new nitrogen heterocyclic systems combining
chromone moiety and 1,2,4-triazole or 1,2,4-triazine in one molecular
frame through an azomethine linkage to examine their antimicrobial
activity.
Received 11 July 2008; accepted 13 November 2008.
Address correspondence to Magdy A. Ibrahim, Department of Chemistry, Fac-
ulty of Education, Ain Shams University, Roxy 11711, Cairo, Egypt. E-mail:
magdy ahmed1977@yahoo.com
2945

2946
M. A. Ibrahim and K. M. El-Mahdy
RESULTS AND DISCUSSION
Condensation reaction of 2-amino-3-formylchromone (1) with some hy-
drazine derivatives 2a–e in boiling absolute ethanol containing a cat-
alytic amount of acetic acid gave the corresponding hydrazones 3a–e.
Refluxing of 3a–e in DMF yielded the same product in all cases, which
was identified as chromeno[2,3-c]pyrazol-4(1H)-one (5)20 (Scheme 1).
Alternatively, condensation of aldehyde 1 with hydrazine hydrate in
boiling DMF produced compound 5 and not the hydrazone 4, which was
obtained previously by Ghosh et al.21 Formation of 5 was explained via
cyclization of hydrazones 3a–e with loss of one molecule of ammonia,
followed by cleavage of amido and thioamido groups22 in high boil-
ing solvents (Scheme 1). The IR spectrum of compound 5 revealed an
absorption band at 3202 cm−1 assigned to a NH group. Moreover, in
the mass fragmentation patterns of hydrazones 3a,b, as examples, the
fragment at m/z 186 (corresponding to chromenopyrazolone 5) was ob-
served while the fragment at m/z 203 (corresponding to hydrazone 4)
was not observed.23–25 These results confirm cyclization with loss of
ammonia at first, followed by cleavage of the –CXR group as amide or
thioamide.
Thiocarbohydrazone 3e was used as a starting material for building
of some new isolated heterocyclic systems connected with the chromone
SCHEME 1

New Heterocyclic Schiff Bases
2947
SCHEME 2
moiety at the position 3. Thus, heating thiocarbohydrazone 3e under
reflux with benzoyl chloride in pyridine gave 2-amino-3-{[(3-phenyl-
5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)imino]
methyl}chromone
(6), while boiling with acetic anhydride afforded N-(3-{[3-methyl-
5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]imino}methyl-4-oxo-4H-
chromene-2-yl)acetamide (7). Also, reaction of 3e with carbon disulfide
in boiling pyridine afforded 2-amino-3-{[(3,5-dithioxo-1,2,4-triazolidin-
4-yl)imino]methyl} chromone (8) (Scheme 2). The structures of 6–8
were confirmed by their elemental analysis and spectral data.
On the other hand, the starting compound 3e was used for construc-
tion of some new Schiff bases bearing 1,2,4-triazine moiety through
the reaction with 1,2-bifunctional electrophiles. Thus, heterocycliza-
tion of 3e with oxalyl chloride, chloroacetyl chloride, phenacyl bro-
mide, bromomalononitrile, and sodium pyruvate led to the formation of
triazinyliminomethylchromones 9–13, respectively (Scheme 3). Com-
pound 13 was authentically obtained by condensation of aldehyde
1 with 4-amino-6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one
(14) in boiling ethanol and few drops of acetic acid (Scheme 3). The IR
1
and H NMR spectra of compounds 9–13 confirmed cyclization of the
side chain, –NHCSNHNH2, in thiocarbohydrazone 3e to 1,2,4-triazine
derivatives 9–13. Heating of the new synthesized compound 9–13 under

2948
M. A. Ibrahim and K. M. El-Mahdy
SCHEME 3
reflux in DMF afforded one product, which was identified as 2-amino-
3-(iminomethyl)-4H-chromen-4-one (15). The formation of compound
15 is assumed to take place through cleavage of the N-N single bond
in high boiling solvents (Scheme 4). The IR spectrum of compound 15
showed absorption bands at 3170, 1629, and 1605 cm−1 assigned to
1
(NH2, NH), (C=O pyrone), and (C=N), respectively. Its H NMR spec-
trum exhibited signals at δ 8.76 (CH=N), 9.20, 10.32, and 10.53 ppm
(NH, NH2).
It is expected that combination of chromone moiety with other
heterocycles may render the resulting compounds more biologically
active.26 Thus, cyclocondensation of aldehyde 1 with 6-amino-1,3-
dimethyluracil-5-carboxaldehyde (16), in boiling ethanol containing
catalytic amount of concentrated sulfuric acid, yielded the diazocine
derivative 17. Under the same conditions, condensation of aldehyde 1
with 2-aminoacetophenone did not give the expected diazocine deriva-
tive 18, but furnished 3-{([(2-acetylphenyl)imino]methyl}-2-amino-4H-
chromen-4-one (19). Similarly, pyrazolyliminomethylchromone 20 was
obtained via reaction of aldehyde 1 with 4-aminoantipyrine under the
same condition (Scheme 5).

New Heterocyclic Schiff Bases
2949
SCHEME 4
SCHEME 5

2950

New Heterocyclic Schiff Bases
2951
BIOLOGICAL ACTIVITY
The new synthesized compounds were screened in vitro for their antimi-
crobial activities, using the standardized disc–agar diffusion method,27
against Staphylococcus aureus and Streptococcus pyogenes as Gram-
positive bacteria, Pseudomonas fluorescens and Pseudomonas phaseoli-
cola as Gram-negative bacteria, and the fungi Fusarium oxysporum and
Aspergillus fumigatus. The antibiotic chloramphencol was used as the
standard reference in the case of Gram-negative bacteria, cephalothin
was used as the standard reference in the case of Gram-positive bacte-
ria, and cycloheximide was used as the standard antifungal reference.
The tested compounds were dissolved in DMF (where this solvent has
no inhibition activity) to obtain concentrations of 100 µ/mL. Uniform
size filter paper disks (3 disks per compound) were impregnated by
an equal volume (10 µL) of dissolved tested compounds and carefully
placed on the incubated 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 of fungi, inhibition
of the organisms, which was evidenced by a clear zone surround each
disk, was measured and used to calculate mean of inhibition zones.27,28
From the results obtained, it is clear that compounds 8 and 20 showed
moderate activity against the test bacteria and high activity against
the tested fungi mainly due to the presence of dithioxo-1,2,4-triazole
and antipyrine moieties. Compounds 9, 13, and 15 showed high activity
toward the tested fungi, while compounds 7 and 19 showed moderate
activity with respect to the references used (Table I).
CONCLUSION
In conclusion, we report herein a convenient route for the synthesis of
some new Schiff bases containing 1,2,4-triazole or 1,2,4-triazine deriva-
tives combined with chromone moiety via the reaction of thiocarbohy-
drazone 3e with some electrophiles. Antimicrobial evaluation revealed
moderate activity.
EXPERIMENTAL
Melting points are uncorrected and were recorded in open capillary
tubes on a Stuart SMP3 melting point apparatus. Infrared spectra
were recorded on a FT-IR Bruker Vector 22 spectrophotometer using
the KBr wafer technique. 1H NMR spectra were measured on a Gemini
spectrometer 200 MHz using DMSO-d6 as solvent and TMS (chemical
shift in δ) as an internal standard. Mass spectra were obtained using a
gas chromatography GCMS qp 1000 ex Shimadzu instrument mass

2952
M. A. Ibrahim and K. M. El-Mahdy
spectrometer (70eV). 2-Amino-3-formylchromone (1)29 and 4-amino-
6-methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one (14)30 were pre-
pared according to the literature.
Formation of Hydrazones 3a–e (General Procedure)
A mixture of aldehyde 1 (0.95 g, 5 mmol) and some hydrazine deriva-
tives (5 mmol), namely benzoylhydrazine (2a, 0.68 g), cyanoacetohy-
drazide (2b, 0.50 g), S-methyl dithiocarbazate (2c, 0.61 g), thiosemi-
carbazide (2d, 0.46 g), and thiocarbohydrazide (2e, 0.53 g), in abso-
lute ethanol (20 mL) containing a few drops of acetic acid, was re-
fluxed for 15 min. The solid obtained after cooling was filtered off
and crystallized from the proper solvent to give compounds 3a–e,
respectively.
N ꢀ-[(2-Amino-4-oxo-4H-chromen-3-yl)methylene]
benzohydrazide (3a)
Crystallized from ethanol, yield (1.3 g, 84%), mp 297◦C, IR (cm−1
,
KBr): 3282, 3213 (NH2, NH), 1666 (2 C=O), 1608 (C=N), 1318 (C=S).
M/z (I.%): 307 (4), 187 (45), 186 (10), 174 (15), 121 (26), 120 (8), 93 (7),
77 (100), 65 (22). Anal. Calcd for C17H13N3O3 (307.31): C, 66.44; H,
4.26; N, 13.67. Found C, 66.43; H, 4.21; N, 13.54.
N ꢀ-[(2-Amino-4-oxo-4H-chromen-3-yl)methylene]-2-
cyanoacetohydrazide (3b)
Crystallized from dioxane, yield (1.1 g, 81%), mp 274–275◦C, IR
(cm−1, KBr): 3285, 3197, 3114 (NH2, NH), 2254 (C≡N), 1681 (2 C=O),
1604 (C=N), 1310 (C=S). M/z (I.%): 270 (15), 204 (9), 187 (95), 186 (37),
174 (38), 121 (100), 93 (30), 68 (71), 65 (51). Anal. Calcd for C13H10N4O3
(270.25): C, 57.78; H, 3.73; N, 20.73. Found C, 57.74; H, 3.71; N, 20.65.
Methyl 2-[(2-Amino-4-oxo-4H-chromen-3-yl)methylene]-
hydrazinecarbodithioate (3c)
Crystallized from ethanol, yield (1.15 g, 78%), mp 313◦C, IR (cm−1
,
KBr): 3297, 3168 (NH2, NH), 1640 (C=O pyrone), 1605 (C=N), 1305
(C=S). Anal. Calcd for C12H11N3O2S (293.37): C, 49.13; H, 3.78; N,
14.32; S, 21.86. Found C, 48.97; H, 3.67; N, 14.24; S, 21.81.
2-Amino-4-oxo-4H-chromene-3-carboxaldehyde
thiosemicarbazone (3d)
Crystallized from acetic acid, yield (0.96 g, 73%), mp 315◦C, IR (cm−1
,
KBr): 3333, 3278, 3206 (NH2, NH), 1644 (C=O pyrone), 1605 (C=N),
1332 (C=S). 1H NMR (δ, DMSO-d6): 7.40 (m, 2H, H6 and H8), 7.71 (d,

New Heterocyclic Schiff Bases
2953
2H, NH2), 7.87 (bs, 1H, NH), 8.00 (d, 2H, H5 and H7), 8.63 (bs, 3H,
CH=N and NH2). Anal. Calcd for C11H10N4O2S (262.29): C, 50.37; H,
3.84; N, 21.36; S, 12.22. Found C, 50.35; H, 3.83; N, 21.14; S; 12.04.
Nꢀꢀ-(2-Amino-4-oxo-4H-chromen-3-yl)methylene]
thiocarbohydrazide (3e)
Crystallized from DMF/H2O, yield (0.84 g, 60%), mp > 320◦C, IR
(cm−1, KBr): 3269, 3209 (2NH2, 2NH), 1642 (C=O pyrone), 1608 (C=N),
1
1315 (C=S). H NMR (δ, DMSO-d6): 5.04 (br, 2H, NH2), 7.39 (m, 2H,
H6 and H8), 7.68 (t, 1H, H7), 8.00 (d, 1H, H5), 8.64 (s, H, CH=N), 8.89
(bs, 1H, NH), 9.66 (d, 2H, NH2), 11.06 (bs, 1H, NH). Anal. Calcd for
C11H11N5O2S (277.31): C, 47.64; H, 4.00; N, 25.25; S, 11.56. Found C,
47.51; H, 3.84; N, 24.94; S, 11.23.
Chromeno[2,3-c]pyrazol-4(1H)-one (5)
A solution of compounds 3a–e (0.5 g) in DMF (15 mL) was refluxed for
2 h. The yellow crystals obtained during heating were filtered off to
give compound 5. Mp > 320◦C, IR (cm−1, KBr): 3202 (NH), 1658 (C=O
pyrone), 1607 (C=N), 1290 (C=S). Anal. Calcd for C10H6N2O2 (186.17):
C, 64.52; H, 3.25; N, 15.05. Found C, 64.32; H, 3.21; N, 14.95.
2-Amino-3-{[(3-phenyl-5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4-
yl)imino] methyl}chromone (6)
Benzoyl chloride (0.3 mL, 2.5 mmol) was added dropwise with contin-
uous stirring to a solution of compound 3e (0.69 g, 2.5 mmol) in dry
pyridine (10 mL). The reaction mixture was refluxed for 4 h. After cool-
ing, the reaction mixture was poured onto ice/HCl. The solid obtained
was filtered off, washed several times with water, and crystallized from
acetic acid to give compound 6 as white crystals. Yield (0.65 g, 72%), mp
> 320◦C, IR (cm−1, KBr): 3442, 3291 (NH2, NH), 1635 (C=O pyrone),
1
1582 (C=N), 1325 (C=S). H NMR (δ, DMSO-d6): 7.45–7.78 (m, 7H,
Ar-H), 7.89 (d, 1H, H8), 8.06 (d, 1H, H5), 8.78 (s, H, CH=N), 9.18 (d,
2H, NH2), 13.69 (s, 1H, NH). Anal. Calcd for C18H13N5O2S (363.40): C,
59.49; H, 3.61; N, 19.27; S, 8.82. Found C, 59.24; H, 3.54; N, 19.12; S,
8.69.
N-(3-{[3-Methyl-5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4-yl}
imino]methyl-4-oxo-4H-chromen-2-yl)acetamide (7)
A mixture of compound 3e (0.69 g, 2.5 mmol) and acetic anhydride (10
mL) was refluxed for 2 h. After cooling, the reaction mixture was poured

2954
M. A. Ibrahim and K. M. El-Mahdy
onto ice. The solid obtained was filtered off, washed several times with
water, and crystallized from DMF to give acetamide 7 as pale brown
crystals. Yield (0.42 g, 49%), mp 236–237◦C, IR (cm−1, KBr): 3423,
3212 (2NH), 1717 (C=O acetyl), 1666 (C=O pyrone), 1612 (C=N), 1302
(C=S). 1H NMR (δ, DMSO-d6): 2.29 (s, 3H, CH3), 2.81 (s, 3H, COCH3),
7.55 (d, 1H, H8), 7.74 (t, 1H, H7), 7.88 (t, 1H, H6), 8.61 (d, 1H, H5),
8.61 (s, 1H, CH=N), 9.15 (s, 1H, NH), 11.28 (s, 1H, NH). Anal. Calcd
for C15H13N5O3S (343.37): C, 52.47; H, 3.82; N, 20.40; S, 9.34. Found C,
52.26; H, 3.72; N, 20.49; S, 9.26.
2-Amino-3-{[(3,5-dithioxo-1,2,4-triazolidin-4-yl)imino}
methyl]chromone (8)
A mixture of compound 3e (0.69 g, 2.5 mmol) and carbon disulfide (0.19
g, 0.15 mL, 2.5 mmol) in dry pyridine (10 mL) was refluxed for 8 h or
until evolution of H2S ceased. After cooling, the reaction mixture was
poured onto ice/HCl. The solid obtained was filtered off, washed several
times with water, and crystallized from DMF/ethanol to give compound
8 as yellow crystals. Yield (0.45 g, 57%), mp > 320◦C, IR (cm−1, KBr):
3285, 3211 (NH2, NH), 1642 (C=O), 1611 (C=N), 1317 (C=S). 1H NMR
(δ, DMSO-d6): 7.43 (t, 2H, H6 and H8), 7.73 (t, 1H, H7), 8.03 (d, 1H, H5),
9.07 (s, 1H, CH=N), 9.31 (bs, 2H, NH2) 9.73 (bs, 2H, 2NH). Anal. Calcd
for C12H9N5O2S2 (319.37): C, 45.13; H, 2.84; N, 21.93; S, 20.08. Found
C, 44.95; H, 2.74; N, 21.75; S, 20.03.
4-{[(2-Amino-4-oxo-4H-chromen-3-yl)methylene]amino}-3-
thioxo-1,2,4-triazin-5,6-dione (9)
Oxalyl chloride (0.22 mL, 0.01 mol) was added dropwise to a suspension
of compound 3e (0.69 g, 2.5 mmol) in dry dioxine (20 mL) and triethy-
lamine (0.5 mL), and refluxed for 6 h. After cooling, the reaction mixture
was poured onto ice. The solid obtained was filtered off, washed several
times with water, and crystallized from DMF/H2O to give compound 9
as yellow crystals. Yield (0.41 g, 50%), mp 295–296◦C. IR (cm−1, KBr):
3267–3211 (NH2, 2NH), 1724 (C=O), 1640 (C=O pyrone), 1608 (C=N),
1
1317 (C=S). H NMR (δ, DMSO-d6): 7.45 (d, 2H, H6, H8), 7.72 (t, 1H,
H7), 8.04 (d, 1H, H5), 8.44 (bs, 1H, OH), 9.16 (d, 2H, NH2), 9.59 (s, 1H,
CH=N), 10.08 (s, 1H, NH). Anal. Calcd for C13H9N5O4S (331.31): C,
47.13; H, 2.74; N, 21.14; S, 9.68. Found C, 46.87; H, 2.68; N, 21.06; S,
9.67.

New Heterocyclic Schiff Bases
2955
4-{[(2-Amino-4-oxo-4H-chromen-3-yl)methylene]amino}-3-
thioxo-1,2,4-triazin-6-one (10)
A mixture of compound 3e (0.69 g, 2.5 mmol) and chloroacetyl chlo-
ride (0.2 mL, 2.5 mmol) in dry pyridine (10 mL) was refluxed for 6 h.
After cooling, the reaction mixture was poured onto ice/HCl. The solid
obtained was filtered off and crystallized from DMF/H2O to give com-
pound 10 as yellow crystals. Yield (0.37 g, 47%), mp > 320◦C. IR (cm−1
,
1
KBr): 3384, 3265, 3163 (NH2, NH, OH), 1622 (C=O pyrone). H NMR
(δ, DMSO-d6): 2.77 (s, 2H, CH2), 7.43 (t, 2H, H6, H8), 7.68 (t, 1H, H7),
7.99 (d, 1H, H5), 8.64 (s, 1H, CH=N), 9.43 (d, 2H, NH2), 11.08 (s, 1H,
NH), 11.61 (s, 1H, OH). Anal. Calcd for C13H11N5O3S (317.33): C, 49.21;
H, 3.49; N, 22.07; S, 10.10. Found C, 49.11; H, 3.36; N, 21.81; S, 10.05.
4-{[(2-Amino-4-oxo-4H-chromen-3-yl)methylene]amino}-5-
phenyl-3-thioxo-2,3-dihydro-1,2,4-triazin-6-one (11)
A mixture of compound 3e (0.69 g, 2.5 mmol) and phenacyl bromide (0.5
g, 2.5 mmol) in dry pyridine (10 mL) was refluxed for 6 h. After cooling,
the reaction mixture was poured onto ice/HCl. The solid obtained was
filtered off and crystallized from DMF/H2O to give compound 11 as
yellow crystals. Yield (0.73 g, 78%), mp > 320◦C. IR (cm−1, KBr): 3350,
1
3193 (NH2, 2NH), 1610 (C=N), H NMR (δ, DMSO-d6): 7.43–8.18 (m,
9H, Ar-H), 8.64 (s, 1H, CH triazine), 8.73 (s, 1H, CH=N), 9.06 (d, 2H,
NH2), 9.34 (s, 1H, NH), 9.77 (s, 1H, NH), Anal. Calcd for C19H15N5O2S
(377.43): C, 60.47; H, 4.01; N, 18.58; S, 8.50. Found C, 60.19; H, 3.96;
N, 18.45; S, 8.42.
5-Amino-4-{[2-amino-4-oxo-4H-chromen-3-
yl)methylene]amino}-3-thioxo-1,2,3,4-
tetrahydro-1,2,4-triazine-6-carbonitrile (12)
A mixture of compound 3e (0.69 g, 2.5 mmol) and bromomalononitrile
(0.36 g, 2.5 mmol) in dry pyridine (10 mL) was refluxed for 6 h. After
cooling, the reaction mixture was poured onto ice. The solid obtained
was filtered off, washed several times with water, and crystallized from
DMF/H2O to give compound 12 as yellow crystals. Yield (0.42 g, 45%),
mp > 320◦C, IR (cm−1, KBr): 3374, 3244, 3146 (2NH2, NH), 2210 (C≡N),
1
1671 (C=O pyrone), 1608 (C=N), 1335 (C=S). H NMR (δ, DMSO-d6):
6.95 (m, 2H, Ar-H), 7.45 (m, 2H, Ar-H), 7.82 (s, 1H, CH=N), 8.86 (d, 2H,
NH2), 9.57 (s, 1H, NH), 10.43 (bs, 2H, NH2), 13.34 (s, 1H, NH). Anal.
Calcd for C14H11N7O2S (341.35): C, 49.26; H, 3.25; N, 28.72; S, 9.39.
Found C, 48.95; H, 3.12; N, 28.51; S, 9.18.

2956
M. A. Ibrahim and K. M. El-Mahdy
4-{[(2-Amino-4-oxo-4H-chromen-3-yl)methylene]amino}-6-
methyl-3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one (13)
Method A
A mixture of compound 3e (0.69 g, 2.5 mmol) and sodium pyruvate
(0.28 g, 2.5 mmol) in glacial acetic acid (15 mL) was refluxed for 4 h. Af-
ter cooling, the reaction mixture was poured onto ice. The solid obtained
was filtered off, washed several times with water, and crystallized from
acetic acid to give compound 13 as white crystals. Yield (0.47 g, 57%),
mp 299–300◦C.
Method B
A mixture of aldehyde 1 (0.95 g, 5 mmol) and 4-amino-6-methyl-
3-thioxo-3,4-dihydro-1,2,4-triazin-5(2H)-one (14)28 (0.28 g, 5 mmol) in
absolute ethanol containing few drops of acetic acid was refluxed for
30 min. The solid obtained during heating was filtered off and crys-
tallized from acetic acid to give compound 13 as white crystals. Yield
(0.75 g, 45%), mp 299–300◦C, IR (cm−1, KBr): 3256, 3137 (NH2, NH),
1
1702 (C=O), 1655 (C=O pyrone), 1608 (C=N), 1292 (C=S). H NMR
(δ, DMSO-d6): 2.19 (s, 3H, CH3), 7.45 (t, 2H, H7, H8), 7.95 (t, 1H, H7),
8.03 (d, 1H, H5), 8.97 (s, 1H, CH=N), 9.63 (d, 2H, NH2), 13.62 (s, 1H,
NH), Anal. Calcd for C14H11N5O3S (329.34): C, 51.06; H, 3.37; N, 4.26;
S, 9.74. Found C, 51.00; H, 3.32; N, 4.15; S, 9.67.
2-Amino-3-(iminomethyl)-4H-chromen-4-one (15)
A solution of compounds 9–13 (0.82 g, 2.5 mmol) in DMF (15 mL) was
refluxed for 4 h. The yellow crystals obtained after cooling were filtered
off and recrystallized from DMF to give compound 15 as yellow crystals.
Mp > 320◦C. IR (cm−1, KBr): 3170 (NH2, NH), 1629 (C=O pyrone), 1605
(C=N). 1H NMR (δ, DMSO-d6): 7.43 (d, 1H, H8), 7.56 (t, 1H, H6), 7.95 (d,
1H, H7), 8.03 (d, 1H, H5), 8.76 (s, 1H, CH=N), 9.20 (s, 1H, NH), 10.32
(bs, 1H, NH), 10.53 (bs, 1H, NH). Anal. Calcd for C10H8N2O2 (188.19):
C, 63.83; H, 4.28; N, 14.89. Found C, 63.16; H, 3.71; N, 14.72.
1,3-Dimethyl-2H-chromeno[2,3-b]pyrimido[4,5-f][1,5]
diazocine-2,4,12-(1H,3H)-trione (17)
A mixture of aldehyde 1 (0.95 g, 5 mmol) and 6-amino-1,3-
dimethyluracil-5-carboxaldehyde (16) (0.46 g, 5 mmol) in absolute
ethanol (50 mL) and few drops of conc. H2SO4, was refluxed for 2 h.
The solid obtained was filtered off and recrystallized from DMF to
give diazocine 17 as yellow crystals. Yield (0.87 g, 52%), mp 301◦C. IR

New Heterocyclic Schiff Bases
2957
(cm−1, KBr): 1743, 1718 (2 C=O), 1664 (C=O), 1607 (C=N). 1H NMR (δ,
DMSO-d6): 3.59 (s, 3H, CH3), 3.72 (s, 3H, CH3), 7.55 (d, 1H, H8), 7.77
(t, 1H, H6), 7.93 (t, 1H, H7), 8.18 (d, 1H, H5), 8.92 (s, 2H, 2 CH=N).
Anal. Calcd for C17H12N4O4 (336.31): C, 60.71; H, 3.60; N, 16.66. Found
C, 60.63; H, 3.53; N, 16.62.
3-{([(2-Acetylphenyl)imino]methyl}-2-amino-4H-chromen-4-
one (19)
A mixture of aldehyde 1 (0.95 g, 5 mmol) and 2-aminoacetophenone
(0.68 g, 5 mmol) in absolute ethanol (50 mL) and few drops of conc.
H2SO4, was refluxed for 4 h. The solid obtained after cooling was fil-
tered off and recrystallized from dioxane to give compound 19 as yel-
low crystals. Yield (0.68 g, 44%), mp 223◦C, IR (cm−1, KBr): 3370, 3263
(NH2), 1678 (C=O acetyl), 1653 (C=O pyrone), 1612 (C=N). 1H NMR
(δ, DMSO-d6): 2.73 (s, 3H, CH3), 6.77–8.12 (m, 7H, Ar-H), 8.35 (d, 1H,
H5), 9.07 (s, 1H, CH=N), 9.45 (d, 2H, NH2). Anal. Calcd for C18H14N2O3
(306.32): C, 70.58; H, 4.61; N, 9.15, Found C, 70.51; H, 4.50; N, 9.03.
4-{[(2-Amino-4-oxo-4H-chromen-3-yl)methylene]amino}-1,5-
dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (20)
A mixture of compound 1 (0.95 g, 5 mmol) and 4-aminoantipyrine (0.51
g, 5 mmol) in absolute ethanol (50 mL) and few drops of conc. H2SO4
was refluxed for 6 h. After cooling, the product was poured onto ice.
The solid obtained was filtered off and recrystallized from acetic acid to
give pyrazolone 20 as yellow crystals. Yield (0.65 g, 35%), mp 167◦C, IR
1
(cm−1, KBr): 3440, 3289 (NH2), 1635 (C=O), 1610 (C=N). H NMR (δ,
DMSO-d6): 3.75 (s, 3H, CH3), 3.88 (s, 3H, CH3), 7.32–8.35 (m, 9H, Ar-
H), 9.13 (d, 2H, NH2), 9.51 (s, 1H, CH=N). Anal. Calcd for C21H18N4O3
(374.40): C, 67.37; H, 4.85; N, 14.96. Found C, 67.25; H, 4.74; N, 14.75.
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