Glycosylation, sugar hydrazones, and antimicrobial evaluation of some 6-substituted-1,2,4-triazines

Article abstract of DOI:10.1080/15257770903454482

Hydrazinolysis of 4-amino-6-[2-(4-methoxyphenyl)vinyl]-3-thioxo-3,4- dihydro-2H-[1,2,4] triazin-5-one (1) gave the corresponding hydrazino derivatives (2) Cyclocondensation of (2) with carbon disulfide furnished 8-amino-6-[2-(4-methoxyphenyl)vinyl]-3-thio

Full text of DOI:10.1080/15257770903454482

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Glycosylation, Sugar Hydrazones, and
Antimicrobial Evaluation of Some 6-
Substituted-1,2,4-Triazines
A. A. El-Barbary a , Y. A. Hafiz a & M. S. Abdel-Wahed a
a Chemistry Department, Faculty of Science, Tanta University, Tanta,
Egypt
Published online: 21 Dec 2009.
To cite this article: A. A. El-Barbary , Y. A. Hafiz & M. S. Abdel-Wahed (2009): Glycosylation, Sugar
Hydrazones, and Antimicrobial Evaluation of Some 6-Substituted-1,2,4-Triazines, Nucleosides,
Nucleotides and Nucleic Acids, 29:1, 55-71
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Nucleosides, Nucleotides and Nucleic Acids, 29:55–71, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257770903454482
GLYCOSYLATION, SUGAR HYDRAZONES, AND ANTIMICROBIAL
EVALUATION OF SOME 6-SUBSTITUTED-1,2,4-TRIAZINES
A. A. El-Barbary, Y. A. Hafiz, and M. S. Abdel-Wahed
Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
Hydrazinolysis of 4-amino-6-[2-(4-methoxyphenyl)vinyl]-3-thioxo-3,4-dihydro-2H-[1,2,4]
2
triazin-5-one (1) gave the corresponding hydrazino derivatives (2) Cyclocondensation of
(2) with carbon disulfide furnished 8-amino-6-[2-(4-methoxyphenyl)vinyl]-3-thioxo-2,8-
dihydro-3H-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-one (3) which was treated with 2,3,4,6-
tetra-O-acetyl-α-D-glucopyranosyl bromide (4) in pyridine to give the corresponding N-glucosyl
derivative 5, which deblocked to give 8. Compound 2 was reacted with isatin 9 and/or isatoic
anhydride 10 to afford 11 and 12. Treatment of 11 and 12 with (4) in pyridine gave the
corresponding mono glucosyl derivatives 13 and 14, which were deblocked by ammonia and
afforded 15 and 16. Condensation of 2 with aldoses afforded the corresponding cyclic products
17a-f and with D-fructose furnished 18. Acetylation of 17b, d afforded the corresponding polyacetyl
derivatives 19b,d. Compound 2 condensed with some aromatic aldehydes in boiling methanol and
gave 20a–f. The newly synthesized compounds were tested as antimicrobial agents.
Keywords Hydrazinolysis; glycosides; sugar hydrazones; antibacterial activity
INTRODUCTION
1,2,4-Triazine ring systems have been reported as potential biologically
active agents.[1] As a kind of widely used biologically active compound,
derivatives of triazinone compounds exhibit anticancer, antiulcer, and anti-
inflammatory effects. In the agricultural field, this class of compounds shows
activities, such as insecticides, herbicides, plant growth regulators, and
increasing crop yields.[2,3] Moreover, 1,2,4-triazine derivatives have been in-
vestigated for some time for their effects on the central nervous system.[4–6]
In the last decade, numerous fused 1,2,4-triazines have been synthesized and
Received 13 April 2009; accepted 29 October 2009.
Thanks are due to Dr. Abdel-Rehem El-Shanshory Professor of Microbiology, Botany ;Department,
Faculty of Science, Tanta University, Tanta, Egypt, for Antimicrobial Testing.
Address correspondence to M. S. Abdel-Wahed, Chemistry Department, Faculty of Science, Tanta
University, Tanta 31527, Egypt. E-mail: msa paper@yahoo.com
55

56
A. A. El-Barbary et al.
SCHEME 1 Synthesis of 3-hydrazino-1,2,4-triazine derivative.
screened in vitro, revealing their anti-HIV and anti-cancer activities[7–11] as
well as selective weed control in wheat, antibacterial, antiviral, antifungal,
anti-inflammatory, anticonvulsant activities, and carrageen induced edema
inhibitor.[12–14]
RESULTS AND DISCUSSION
Different carbohydrazides were found to be useful as medicaments
especially in the treatment of inflammatory and autoimmune diseases, os-
teoarthritis, respiratory diseases, tumors, cachexia, cardiovascular diseases,
fever, hemorrhage, and sepsis. Carbohydrazides and related compounds
exhibited antifungal, antiviral, and bacteriostatic.[15] Accordingly, hydrazi-
nolysis of compound 1 could be achieved by its treatment with a boiling
mixture of hydrazine, MeOH/DMF to afford 4-amino-3-hydrazino-6-[2-(4-
methoxyphenyl)vinyl]-4H-[1,2,4]triazin-5-one (2) (Scheme 1).
Cyclocondensation of 2 with carbon disulfide in pyridine at 80◦C
was achieved to afford 8-amino-6-[2-(4-methoxyphenyl)vinyl]-3-thioxo-2,8-
dihydro-3H-[1,2,4] triazolo[4,3-b][1,2,4]triazin-7-one (3). The structure of
1
3 was established with spectroscopic data. Its H NMR spectrum showed a
singlet at δ 8.35 assigned to NH proton, which appear at 3455 cm−1 in its IR
spectrum (Scheme 2).
Direct glycosidation of compound 3 was reported to offer a convenient
selective synthesis of the 2-glycosyl derivative.[16,17] So, coupling of 3 with
2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (4) in pyridine afforded
8-amino-6-[2-(4-methoxyphenyl) vinyl]-3-thioxo-7,8-dihydro-2-(2,3,4,6-tetra-
O-acetyl-β-D-glucopyranosyl)-1,2,4-triazolo[4,3-b][1,2,4]triazine-7-one (5)
as the sole product (TLC; Scheme 2).
The anomeric proton of similar β-N- glucosides having an adjacent C S
was reported to appear more down field than that for the β-S-glucosides due
to the anisotropic deshielding effect of the C S.[18–23] So the position of the
ꢁ
anomeric proton at δ 5.25 with J 1 = 8.93 Hz confirmed the β-N- structure
of compound 5 and excluded the possible isomeric β-S- structure of
compound 6. The mass spectrum of 5 showed the parent ion peak at m/z =
646 (M+, 6.30%; Scheme 2).

Glycosylation of Some 6-Substituted-1,2,4-triazines
57
SCHEME 2 Coupling of 3 with acetyl-D-glucopyranosyl bromide derivative.
Oxidation of 5 with potassium permanganate at 25◦C furnished 8-
amino-6-[2-(4-methoxyphenyl)vinyl]-7,8-dihydro-2-(2,3,4,6-tetra-O-acetyl-β-
D-glucopyranosyl)-1,2,4-triazolo[4,3-b][1,2,4]triazine-3,7-dione (7), whose
IR spectrum showed (2 C O) at 1600 and 1680 cm−1(Scheme 3).
Deblocking of 5 was achieved by its treatment with ammonia so-
lution at r.t to afford 8-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-thioxo-2-
(β-D- glucopyranosyl)-2,8-dihydro-3H-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-
one (8). Its 1H NMR spectrum showed a doublet at δ 5.19 ppm assigned to
ꢁ
the anomeric proton of the glucose moiety with J 1 = 9.13 Hz according
ꢁ
ꢁ
to a diaxial orientation of H1 and H2 protons, which confirmed its β-
configuration[24] (Scheme 3).
The Schiff bases of isatin were investigated for their pharmaceu-
tical properties[25] and Isatoic anhydride possesses some synthetic po-
tential in this respect due to its ability to undergo various cyclization
reactions.[26] Thus, condensation of 2 with isatin 9 and/or isatoic an-
hydride 10 in anhydrous boiling dioxane furnished 3-({4-amino-6-[2-(4-

58
A. A. El-Barbary et al.
SCHEME 3 Oxidation of compound 5.
methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4]triazin-3-yl} hydrazono)-1,3-
dihydro-indol-2-one (11) and 3-{4-amino-6-[2-(4-methoxyphenyl)vinyl]-5-
oxo-4,5-dihydro[1,2,4]triazin-3-ylamino}-1H-quinazoline-2,4-dione (12), re-
spectively (Scheme 4). Compounds 11 and 12 were elucidated by spectro-
scopic data. Thus, infrared (IR) spectrum of 11 showed, (2 CO) bands at
1613 and 1716 cm−1 and 1H NMR spectrum showed a doublet (2H, 2 NH)
at 8.45 ppm. The mass spectrum of 11 showed the parent ion peak at m/z =
403 (M+, 100%).
Similarly, IR spectrum of 12 showed, (3 CO) bands at 1500, 1595, and
1
1640 cm−1 and its H NMR spectrum showed a singlet (2H, 2 NH) at 6.18
ppm. In addition, its mass spectrum showed the parent ion peak at m/z =
419 (M+, 17.20%; Scheme 4).
Coupling compounds 11 and/or 12 with (4) in pyridine at
room temperature gave 6-[3-({4-amino-6-[2-(4-methoxyphenyl)vinyl]-5-
oxo-4,5- dihydro[1,2,4]triazin-3-yl} hydrazono)-1-(2,3,4,6-tetra-O-acetyl-β-
D- glucopyranosyl)-2,3-dihydroindole-2-one (13) and 6-(3-{4-amino-6-[2-
(4-methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4] triazin-3-ylamino}-1-(2,3,
4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1H-quinazoline-2,4-dione (14), re-
1
spectively. The H NMR spectra of 13 and 14 showed the position of the
ꢁ
anomeric protons at δ 4.25 and 4.67 with J 1 = 9.35 and 9.59 Hz confirmed
the β-N- structure of 13 and 14 in addition to the presence of OAc groups
at the range 2.09–2.58 ppm. Their IR spectra showed bands at the range
1748–1750 cm−1 (OAc; Scheme 5).
Deblocking of 13 and/or 14 was achieved by their treatment with
ammonia solution at room temperature to afford 3-({4-Amino- 6-[2-(4-

Glycosylation of Some 6-Substituted-1,2,4-triazines
59
SCHEME 4 Condensation of 2 with isatin and/or isatoic anhydride.
methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4 ] triazin -3-yl}hydrazono) - 1 -
(β-D-glucopyranosyl)-1,3-dihydroindol-2-one (15) and 3-4- Amino-6-[2-(4-
methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4] triazin-3-ylamino}-1-(β-D-
glucopyranosyl)-1H-quinazoline-2,4-dione (16), respectively (Scheme 5).
The 1H NMR spectra of 15 and 16 showed the position of the anomeric
ꢁ
protons at δ 4.82 and 4.80 ppm with J 1 = 9.18 and 9.23 Hz confirmed the
β-N-structure of 15 and 16 in addition to the presence of (OH) groups
at the range 3.38–3.97 ppm. Their IR spectra showed bands at the range
3396–3746 cm−1 (OH) (Scheme 5).
Compound 2 was reacted with some aldoses namely, D-glucose, D-
galactose, D-mannose, D-ribose, L-arabinose and/or D-xylose in anhydrous
boiling dioxane to yield the corresponding sugar hydrazones 4-amino-6-
[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(polyhydroxyhexylidene)hydrazinyl]-4H-
[1,2,4]triazin-5-one 17a–f (Scheme 6).
The structure of compounds 17a–f was confirmed by spectral evidences.
1
The H NMR spectra showed structure 17a–f fitted with the recorded
1
data. For example, the H NMR spectrum of 17a showed a signal at 5.72
ppm (1H) corresponded to (NH) proton and a signal at 7.69 ppm (1H)
1
corresponded to CH N. The H NMR spectra of 17b–f showed similar
patterns to that discussed above (Scheme 6).
Similarly, compound 2 reacted with D-fructose under the same reaction
conditions to give 4-amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(2,3,4,5-

60
A. A. El-Barbary et al.
SCHEME 5 Coupling of 11 and/or 12 with acetyl-D-glucopyranosyl bromide derivative.
tetrahydroxy-1-hydroxymethylpentylidene)hydrazine]-4H-[1,2,4]triazin-5-
one (18) (Scheme 7).
Acetylation of the sugar hydrazones 17b,d with acetic anhydride in
anhydrous pyridine at room temperature afforded the polyacetyl derivatives
1
19b,d (Scheme 8). The H NMR spectra of the products 19b,d confirmed
the presence of OAc groups in addition to the NAc group. Their IR spectra
showed bands at 1630–1670 (NAc) and 1684–1746 cm−1 (OAc).
Compound 2 condensed with some aromatic aldehydes in boiling
methanol and gave the corresponding hydrazones 20a–f. Their structures
could be assigned as two tautomeric forms i and ii. Both tautomers were
1
observed in the H NMR spectra where the signals correspond to the

Glycosylation of Some 6-Substituted-1,2,4-triazines
61
SCHEME 6 Condensation of 2 with some aldoses.
SCHEME 7 Reaction of 2 with D-fructose.
SCHEME 8 Acetylation of 17b,d.

62
A. A. El-Barbary et al.
SCHEME 9 Condensation of 2 with some aldehydes.
CH NH and CH N groups are all present. This indicates the presence
of a ring-chain tautomerism and the two tautomers coexist in a dynamic
equilibrium (Scheme 9).
1
As an example, the H NMR spectrum of compound 20a showed a
signal at 5.42 ppm corresponds to NH2 protons and a signal at 10.41 ppm
corresponds to CH N proton. Its IR spectrum showed a sharp band at 3238
cm−1 attributed to the presence of NH2 group.
BIOLOGICAL ACTIVITY
The newly synthesized compounds were screened for their in vitro
antibacterial activities using the cut plug method[27] against the gram
positive bacteria (Bacillus subtilius and Staphylococcus aureus) and the gram
negative bacteria (Escherichia coli, Salmonella typhae, and Klebsilla sp.) and
antifungal activity against yeast (Candida albicans) using Chloramophenicol
and Streptomycin as standard drugs. The results are summarized and
illustrated in Table 1.
The results revealed that most of the tested compounds showed antibac-
terial or/and antifungal (anticandidal) activity with varying magnitudes.
The zone of inhibition above 7 mm in diameters was taken as a positive
result.
Compounds 17a–f and 18 showed low antimicrobial activities, except
17c. The effect differed according to the presence of polyhydroxy side
chain.
Compound 20e showed only antibacterial but not antifungal activity.
On the other hand, compound 20f showed the highest antibacterial and
antifungal effect may be due to the presence of a pyridyl ring.

Glycosylation of Some 6-Substituted-1,2,4-triazines
63
TABLE 1 Diameters of inhibition zones (mm) of newly synthesized triazines against different test
bacteria on nutrient agar and yeast after 24 hours by the cut-plug method on nutrient agar at 35–37◦C
Tasted organisms
Escherichia
coli
Bacillus
subtilus
Staphylococcus Salmonella
Candida
albicans
Cpd.
aurus
typhae
Klebsilla sp.
Chloramophenicol
(30 µgm)
Streptomycin
(10 µgm)
(1)
(2)
(3)
(5)
(8)
(11)
(12)
(13)
(14)
(15)
(16)
20
14
20
23
38
—
23
11
—
—
12
—
12
10
17
17
17
—
9
10
—
—
10
15
13
—
15
—
—
17
15
—
—
—
—
8
—
20
20
17
10
—
7
—
—
9
—
15
25
—
—
—
—
10
—
—
—
11
12
—
15
10
—
20
18
—
—
—
—
—
11
25
10
10
17
13
17
—
—
—
—
—
—
13
11
—
15
—
13
10
13
15
—
—
—
—
10
45
12
20
17
15
17
—
—
—
—
15
10
12
—
—
15
—
—
13
15
—
—
—
—
—
—
35
10
25
25
20
15
—
10
—
—
10
15
13
12
—
15
11
12
20
10
15
—
—
—
8
9
(17a)
(17b)
(17c)
(17d)
(17e)
(17f)
13
12
—
20
—
—
8
17
—
—
—
—
—
12
35
(18)
(19b)
(19d)
(20a)
(20b)
(20c)
(20d)
(20e)
(20f)
10
40
—
40
EXPERIMENTAL
All melting points are uncorrected and performed by the open capillary
melting point apparatus. Microanalyses were performed by Microanalysis
Unit, Faculty of Science, Tanta University, Egypt. IR spectra were recorded
with a Perkin-Elmer spectrometer (Perkin-Elmer, Waltham, MA, USA).
The NMR spectra were recorded on a Bruker 300 MHz and Bruker 200
MHz spectrometer (Bruker, Bellerica, MA, USA) using TMS as an internal
standard, DMSO and CHCl3 as solvents. Mass spectra (MS) were recorded
using electron ionization (E.I.) on a Varian Mat 311A spectrometer.
Compound 1 was prepared according to literature method.[28]
Compound 2 was prepared according to literature method.[29]

64
A. A. El-Barbary et al.
8-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-thioxo-2,8-dihydro-3H
[1,2,4]triazolo [4,3-b][1,2,4]triazin-7-one (3)
Compound 2 (2.74 g, 0.01 mol) and carbon disulfide (10 ml) in
anhydrous pyridine (25 ml) was refluxed for 5 hours (TLC). The solvent
was removed under vacuo and the residue was refluxed for 1 hour in acetic
acid and cooled, the solid product formed was filtered off, and recrystallized
from DMF/EtOH to give compound 3. (72.8%); m.p. 151–152◦C; IR (KBr),
1601 (CN), 2933 (CH), 3455(NH) cm−1; 1H NMR (DMSO-d6): δ 3.75 (s, 3H,
CH3O-4), 3.82 (s, 2H, NH2), 7.11–7.93 (m, 6H, Harom), 8.35 (s, 1H, NH).
Anal. For C13H12N6O2S Calcd.: C, 49.36; H, 3.82; N, 26.57. Found: C,
49.33; H, 3.79; N, 26.48.
8-amino-6-[2-(4-methoxyphenyl)vinyl]-3-thioxo-7,8-dihydro-2-
(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1,2,4-triazolo[4,3-
b][1,2,4]triazine-7-one (5)
To a suspension of compound 3 (3.16g, 0.01 mol) in anhydrous pyridine
(15 ml), 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide (4) (4.1g, 0.01
mol) was added with stirring and cooling to 10◦C over a period of 10
minutes. The stirring was continued at room temperature overnight (TLC).
The reaction mixture was poured onto ice water. The solid obtained was
filtered off, dried and recrystallized from DMF to afford 5. (61%); m.p.
219–220◦C; MS: m/z 646 (M+, 6.30); IR (KBr), 1603 (CN), 1640 (C = ON),
1783 (C = OO) cm−1; 1H NMR (DMSO-d6) δ 2.15, 2.27, 2.29, 2.37 (4s, 12H,
ꢁ
ꢁ
ꢁ
4Ac), 3.53 (s, 3H, OCH3), 3.95 (dd, 1H, J H-5 -H-4 = 2.13 Hz, J H-5 -H-5ꢁꢁ = 11.23
Hz, H-5ꢁ), 4.11 (t, 1H, J = 2.33 Hz, H-4ꢁ), 4.53 (dd, 1H, J H-3 -H-4 = 3.19 Hz,
ꢁ
ꢁ
J H-3 -H-2 = 10.00 Hz, H-3ꢁ), 4.99 (dd, 1H, (J H-2 -H-1 + J H-2 -H-3 )/2 = 7.14 Hz,
H-2ꢁ), 5.25 (d, 1H, J ꢁ = 8.93, H-1ꢁ), 5.61 (s, 2H, NH2),7.44–7.89 (m, 6H,
Harm).
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
Anal. For C27H30N6O11S Calcd.: C, 50.15; H, 4.68; N, 12.75. Found: C,
50.07; H, 4.63; N, 13.00.
8-amino-6-[2-(4-methoxyphenyl)vinyl]-7,8-dihydro-2-(2,3,4,6-tetra-
O-acetyl-β-D-glucopyranosyl)-1,2,4-triazolo[4,3-b][1,2,4]triazine-
3,7-dione (7)
To a solution of 5 (6.46 g, 0.01 mol) in glacial acetic acid (25 ml), a
solution of potassium permanganate (0.3 g, 0.02 mol) in water (10 ml) was
added gradually with stirring for 30 minutes. Stirring was continued for 5
hours at room temperature, and the mixture was then poured onto crushed
ice. The resulting solid was collected and recrystallized from DMF to afford
7. (65%); m.p. 232–235◦C; IR (KBr), 1600 and 1680 (2 CO), 2987 (CH),
3183 (NH2) cm−1.

Glycosylation of Some 6-Substituted-1,2,4-triazines
65
Anal. For C27H30N6O12 Calcd.: C, 51.43; H, 4.80; N, 13.33. Found: C,
51.22; H, 4.73; N, 13.09.
8-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-thioxo-2-(β-D-
glucopyranosyl)-2,8-dihydro-3H-[1,2,4]triazolo[4,3-b][1,2,4]triazin-
7-one (8)
Stirring of compound 5 (6.46 g, 0.01 mol) in ammonia solution (20
ml) overnight until the starting material was consumed (TLC). The solid
obtained was filtered, dried and recrystallized from ethanol to afford 8.
(78%); m.p. 195–196◦C; IR (KBr), 1614 (CN), 3353 (NH2), 3499 (OH)
cm−1; 1H NMR (DMSO-d6) δ 3.71(s, 3H, OCH3), 4.08–4.47 (m, 4H, 4OH),
4.55 (dd, 1H, J = 7.08 Hz, H-5ꢁ), 4.91 (d, 1H, J = 2.37 Hz, H-4ꢁ), 5.09 (d,
1H, J = 2.98 Hz H-3ꢁ), 5.19 (d, 1H, J = 9.13 Hz H-1ꢁ,2ꢁ), 5.28 (s, 2H, NH2),
5.38 and 5.54 (s, 2H, H-1ꢁ, 2ꢁ), 7.68–8.23 (m,6H,Harm).
Anal. For C19H22N6O7S Calcd.: C, 47.69; H, 4.63; N, 17.44. Found: C,
47.55; H, 4.57; N, 17.44.
Reaction of 2 with Isatin and Isatoic Anhydride: Formation of 11
and 12
A mixture of 2 (2.74 g, 0.01 mol) and isatin or isatoic anhydride (0.01
mol) was refluxed in dioxane (25 ml) for 3–5 hours (TLC). The solvent was
removed under vaccuo and the residue was recrystallized from DMF/water
to give 11 and 12, respectively.
3-({4-Amino-6-[2-(4-methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4]
triazin-3-yl} hydrazono)-1,3-dihydro-indol-2-one (11). (96%); m.p. > 300◦C;
MS: m/z 403 (M+, 100); IR (KBr), 1613 and 1716 (2CO), 3212 (NH2),
1
3303 (NH) cm−1; H NMR (DMSO-d6) δ 3.42 (s, 3H, CH3O-4), 5.67 (s,
2H, NH2), 6.81 (t, 2H, J = 4.4 Hz, Harom), 7.18 (t, 2H, J = 7.7 Hz, Harom),
7.54 (d, 2H, J = 3.6 Hz, Harom), 7.61 (q, 2H, J = 4.3 Hz, Harom), 7.76 (d,
2H, J = 8.3 Hz, Harom), 8.45 (d, 2H, 2NH), 10.59 (s, 1H, OH). Anal. For
C20H17N7O3 Calcd.: C, 59.55; H, 4.25; N, 24.31. Found: C, 59.47; H, 4.17;
N, 24.22.
3-{4-Amino-6-[2-(4-methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4]
triazin-3-ylamino}-1H-quinazoline-2,4-dione (12). (80%); m.p. 284–286◦C;
MS: m/z 419 (M+, 17.20); IR (KBr), 1500, 1595 and 1640 (3CO), 3263
(NH2), 3437 (NH) cm−1; 1H NMR (DMSO-d6) δ 3.45 (s, 3H, CH3O-4), 5.23
(s, 2H, NH2), 6.18 (s, 2H, 2NH), 7.25–7.78 (m, 10H, Harom). Anal. For
C20H17N7O4 Calcd.: C, 57.28; H, 4.09; N, 23.38. Found: C, 57.12; H, 4.19;
N, 22.86.

66
A. A. El-Barbary et al.
Reaction of Compound 11 and/or 12 with (4): Formation of 13 and
14
To a suspension of compounds 11 and/or 12 (0.01 mol) in anhydrous
pyridine (15 ml), (4) (4.1g, 0.01 mol) was added with stirring and cooling
to 10◦C over a period of 10 minutes. The stirring was continued at room
temperature overnight (TLC). The reaction mixture was poured onto ice,
and the solid obtained was filtered off, dried, and recrystallized from DMF
to afford 13 and 14.
6-[3-({4-amino-6-[2-(4-methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4]
triazin-3-yl}hydrazono)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-2,3-
dihydroindole-2-one (13). (63%); m.p. 260–262◦C; IR (KBr), 1605 (CN),
1
1750 (C OO), 3424 (NH) cm−1; H NMR (DMSO-d6) δ 2.38, 2.43, 2.49,
2.58 (4s, 12H, 4Ac), 3.22 (s, 3H, CH3O-4), 3.82 (s, 2H, NH2), 4.11–4.25
ꢁ
(m, 7H, Hpyran, J 1 = 9.35 Hz), 6.99–7.23 (m, 4H, Harm), 7.25–7.48 (m, 6H,
Harm), 8.23 (s, 1H, NH). Anal. For C34H35N7O12 Calcd.: C, 55.66; H, 4.81;
N, 13.36. Found: C, 55.23; H, 4.79; N, 13.27.
6-(3-{4-amino-6-[2-(4-methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4]
triazin-3-ylamino}-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-1H-
quinazoline-2,4-dione (14). (50%); m.p. 269–270◦C; IR (KBr), 1626
(CN), 1691 (C = O), 1748 (C = OO) cm−1; 1H NMR (DMSO-d6) δ 2.09,
2.18, 2.23, 2.26 (4s, 12H, 4Ac), 3.14 (s, 3H,CH3O-4), 3.92 (s, 2H, NH2),
ꢁ
4.21, 4.36, 4.45, 4.59, 4.67 (5s, 7H, Hpyran, J 1 = 9.59 Hz), 6.60–6.88 (m,
10H, Harom), 8.13 (s, 1H, NH). Anal. For C35H37N7O13 Calcd.: C, 55.04; H,
4.80; N, 12.84. Found: C, 55.11; H, 4.69; N, 12.77.
Deblocking of Compounds 13 and/or 14
Compounds 13 and/or 14 (0.01 mol) were stirred at room temperature
with ammonia solution (20 ml) over night (TLC). The solid obtained was
filtered off, dried and recrystalized from ethanol to afford 15 and 16.
3-({4-Amino-6-[2-(4-methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4]
triazin-3-yl}hydrazono)-1-(β-D-glucopyranosyl)-1,3-dihydroindol-2-one (15).
(81%); m.p. 209–211◦C; IR (KBr), 1592 (CN), 3238 (NH2), 3392 (OH)
cm−1; 1H NMR (DMSO-d6) δ 3.15 (s, 3H, CH3O-4), 3.38–3.72 (m, 4H, OH),
ꢁ
4.08 (s, 2H, NH2), 4.33, 4.42, 4.51, 4.69 and 4.82 (5s, 7H, Hpyran, J1 = 9.18
Hz), 6.39–6.58 (m, 4H, Harom), 6.61- 6.78 (m, 6H, Harm),7.91 (s, 1H, NH).
Anal. For C26H27N7O8 Cacld.: C, 55.22; H, 4.81; N, 17.34. Found: C, 54.98;
H, 4.77; N, 17.14.
3-{4-Amino-6-[2-(4-methoxyphenyl)vinyl]-5-oxo-4,5-dihydro[1,2,4]
triazin-3-ylamino}-1-(β-D-glucopyranosyl)-1H-quinazoline-2,4-dione
(16).
(89%); m.p. 225–226◦C; IR (KBr), 1595 (CN), 3398 (NH2), 3746 (OH)
cm−1; 1H NMR (DMSO-d6) δ 3.24 (s, 3H, CH3O-4), 3.57–3.97 (m, 4H, OH),
4.18 (s, 2H, NH2), 4.41, 4.57, 4.61, 4.63 and 4.80 (5s, 7H, Hpyran, J 1 = 9.23
ꢁ

Glycosylation of Some 6-Substituted-1,2,4-triazines
67
Hz), 6.71–6.89 (m, 4H, Harom), 6.92–7.10 (m, 6H, Harom),8.07 (s, 1H, NH).
Anal. For C27H29N7O9 Calcd.: C, 54.45; H, 4.91; N, 16.46. Found: C, 54.33;
H, 4.87; N, 16.18.
Condensation of 2 with Free Sugars: Formation of 17a–f and 18
General Procedure
A mixture of 2 (2.74 g, 0.01 mol) and aldohexoses, namely: D-glucose,
D-galactose, D-mannose, aldopentoses, namely: D-ribose, L-arabinose, D-
xylose, and/or fructose (0.01 mol) was refluxed in dioxane (20 ml) for 4
horus (TLC). After cooling, the precipitated solid was filtered off, washed
with ethanol and recrystallized from DMF to afford 17a–f and 18.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(2,3,4,5,6-pentahydroxy-
hexylidene)hydrazine]-4H-[1,2,4]triazin-5-one (17a). Using D-glucose in
the general procedure gave 17a. (82%); m.p. 195–196◦C; IR (KBr), 1600
(CN), 3208 (NH2), 3425 (OH) cm−1; 1H NMR (DMSO-d6) δ 2.51 (s, 3H,
CH3O-4), 3.67–3.75 (m, 4H, OH), 3.89 (s, 1H, OH), 4.35 (d, 2H, J = 5.36
Hz, H-5ꢁ), 4.49 (dd, 1H, J = 2.97 Hz, H-4ꢁ), 4.85 (dd, 1H, J H-3 -H-4 = 2.18
ꢁ
ꢁ
Hz, J H-3 -H-2 = 9.36 Hz, H-3ꢁ), 5.03 (t, 1H, J = 2.07, H-2ꢁ), 5.25 (s, 2H, NH2),
5.68 (d, 1H, J = 2.78, H-1ꢁ), 5.72 (s, H, NH), 6.91–7.13 (m, 6H, Harom), 7.69
(s, 1H, N = CH). Anal. For C18H24N6O7 Calcd.: C, 49.54; H, 5.54; N, 19.26.
Found: C, 49.98; H, 5.72; N, 18.67.
ꢁ
ꢁ
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(2,3,4,5,6-pentahydroxy-
hexylidene)hydrazine]-4H-[1,2,4]triazin-5-one (17b). Using D-galactose in
the general procedure gave 17b. (88%); m.p. 177–179◦C; MS: m/z 436
(M+, 16.30); IR (KBr), 1590 (CN), 3248 (NH2), 3368 (OH) cm−1; 1H NMR
(DMSO-d6) δ 2.95 (s, 3H, CH3O-4), 4.11–4.58 (m, 5H, OH), 4.77 (m, 2H,
H-5ꢁ), 5.38 (d, 1H, J = 2.76 Hz, H-4ꢁ), 5.61 (d, 1H, J = 2.99 Hz, H-3ꢁ), 5.91
(d, 1H, J = 2.33 Hz, H-2ꢁ), 6.11 (d, 1H, J = 2.93 Hz, H-1ꢁ), 6.35 (s, 2H,
NH2), 6.62 (s, H, NH), 7.38–7.63 (m, 6H, Harom), 8.38 (s, 1H, N = CH).
Anal. For C18H24N6O7 Calcd.: C, 49.54; H, 5.54; N, 19.26. Found: C, 49.38;
H, 5.49; N, 19.16.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(2,3,4,5,6-pentahydroxy-
hexylidene)hydrazine]-4H-[1,2,4]triazin-5-one (17c). Using D-mannose in
the general procedure gave 17c. (76%); m.p. 183–185◦C; MS: m/z 436 (M+,
25.10); IR (KBr), 1593 (CN), 3375(OH) cm−1; 1H NMR (DMSO-d6) δ 2.74
(s, 3H, CH3O-4), 3.67–4.22 (m, 5H, OH), 4.55 (d, 2H, J = 6.53 Hz, H-5ꢁ),
4.92 (d, 1H, J = 5.19 Hz, H-4ꢁ), 5.25 (dd, 1H, J H-3 -H-4 = 4.57 Hz, J H-3 -H-2
=
ꢁ
ꢁ
ꢁ
ꢁ
12.76 Hz, H-3ꢁ), 5.55 (t, 1H, J = 4.49, H-2ꢁ), 5.75 (d, 1H, J = 7.55, H-1ꢁ),
6.00 (s, 2H, NH2), 6.42 (s, H, NH), 7.06–7.44 (m,6H,Harom), 8.09 (s, 1H, N
= CH). Anal. For C18H24N6O7 Calcd.: C, 49.54; H, 5.54; N, 19.26. Found:
C, 49.43; H, 5.52; N, 19.20.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(2,3,4,5-tetrahydroxypenty-
lidene) hydrazine]-4H-[1,2,4]triazin-5-one (17d). Using D-ribose in the

68
A. A. El-Barbary et al.
general procedure gave 17d. (85%); m.p. 170–171◦C; IR (KBr), 1595 (CN),
3210 (NH2), 3266 (OH) cm−1; 1H NMR (DMSO-d6) δ 2.51 (s, 3H, CH3O-4),
3.69–3.75 (m, 4H, 4OH), 4.42 (d, 1H, J = 5.83 Hz, H-4ꢁ), 4.61 (s, 1H, H-3ꢁ),
4.75 (t, J = 4.86 Hz, H-2ꢁ), 4.91 (d, 1H, J = 3.19 Hz, H-1ꢁ), 5.03 (s, H, NH),
5.24 (s, 2H, NH2), 6.89–7.55 (m,6H, Harom), 7.74 (s, 1H, N = CH). Anal.
For C17H22N6O6 Calcd.: C, 50.24; H, 5.46; N, 20.68. Found: C, 50.11; H,
5.42; N, 20.60.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(2,3,4,5-tetrahydroxypenty-
lidene) hydrazine]-4H-[1,2,4]triazin-5-one (17e). Using L-arabinose in the
general procedure gave 17e. (60%); m.p. 200–201◦C; IR (KBr), 1597 (CN),
3319 (OH) cm−1; 1H NMR (DMSO-d6) δ 2.78 (s, 3H, CH3O-4), 3.65–4.08
(m, 4H, OH), 4.35 (t, 1H, J = 6.85 Hz, H-4ꢁ), 4.62 (t, 1H, J = 5.27 Hz,
H-3ꢁ), 4.82 (d, 1H, J = 3.49 Hz, H-2ꢁ), 4.96 (d, 1H, J = 5.99 Hz, H-1ꢁ), 5.19
(s, H, NH), 5.51 (s, 2H, NH2), 6.74–7.45 (m, 6H, Harom), 7.68 (s, 1H, N =
CH). Anal. For C17H22N6O6 Calcd.: C, 50.24; H, 5.46; N, 20.68. Found: C,
50.23; H, 5.41; N, 20.44.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(2,3,4,5-tetrahydroxypenty-
lidene) hydrazine]-4H-[1,2,4]triazin-5-one (17f). Using D-xylose in the
general procedure gave 17f. (79%); m.p. 172–173◦C; IR (KBr), 1601 (CN),
3267 (NH2), 3449 (OH) cm−1; 1H NMR (DMSO-d6) δ 2.50 (s, 3H, CH3O-4),
3.41–3.78 (m, 4H, 4OH), 4.11 (d, 1H, J = 5.66 Hz, H-4ꢁ), 4.38 (m, 1H,
H-3ꢁ), 4.75 (d, 1H, J = 6.43 Hz, H-2ꢁ), 5.02 (d, 1H, J = 2.83 Hz, H-1ꢁ), 5.23
(s, H, NH), 5.53 (s, 2H, NH2), 6.92–7.55 (m, 6H, Harom), 7.73 (s, 1H, N =
CH). Anal. For C17H22N6O6 Calcd.: C, 50.24; H, 5.46; N, 20.68. Found: C,
50.19; H, 5.39; N, 20.53.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(1,2,3,4-tetrahydroxy-1-
hydroxy- methylpentylidene)hydrazine]-3H-[1,2,4]triazin-5-one (18). Using
D-fructose in the general procedure gave 18. (76%); m.p. 192–194◦C; IR
1
(KBr), 1599 (CN), 3251 (NH2), 3423 (OH) cm−1; H NMR (DMSO-d6) δ
2.49 (s, 3H, CH3O-4), 3.59–4.12 (m, 5H, OH), 4.84 (d, 1H, J = 6.09 Hz,
H-4ꢁ), 5.11 (m, 1H, H-3ꢁ), 5.45 (d, 1H, J = 5.77 Hz, H-2ꢁ), 5.61 (d, 1H, J
= 4.53 Hz, H-1ꢁ), 5.85 (s, 2H, NH2), 6.42 (s, H, NH), 6.82–7.21 (m, 6H,
Harom). Anal. For C18H24N6O7 Calcd.: C, 49.54; H, 5.54; N, 19.26. Found: C,
49.36; H, 5.51; N, 19.07.
Acetylation of 17b,d: Formation of 19b,d
To a suspension of each of 17b,d (0.01 mol) in anhydrous pyridine (10
ml), acetic anhydride (7 ml) was added dropwise with stirring and cooling
to 10◦C over a period of 10 minutes. The stirring was continued at room
temperature overnight (TLC). The reaction mixture was poured onto ice
water. The solid obtained was filtered off, dried, and recrystallized from
ethanol to afford compounds 19b,d.

Glycosylation of Some 6-Substituted-1,2,4-triazines
69
Acetic acid 2,3-diacetoxy-4-(acetyl-{4-amino-6-[2-(4-methoxyphenyl)
vinyl]-5-oxo-4,5-dihydro-[1,2,4]triazin-3-yl}hydrazono)-1-(1,2-diacetoxy-
ethyl) butyl ester (19b). (65%); m.p. 214–215◦C; IR (KBr), 1609 (CN), 1630
(C = ON), 1684 (C = OO) cm−1; 1H NMR (DMSO-d6) δ 2.43–2.98 (6s,
18H, 6Ac), 3.68 (s, 3H, CH3O-4), 4.43 (dd, 2H, J = 7.38 Hz, H-5ꢁ), 4.78 (t,
1H, J = 2.38 Hz, H-4ꢁ), 4.81 (dd, 1H, J H-3 -H-4 = 1.88 Hz, J H-3 -H-2 = 10.57
ꢁ
ꢁ
ꢁ
ꢁ
Hz, H-3ꢁ), 5.23 (dd, 1H, (JH-2 -H-1 + JH-2 -H-3 )/2 = 1.77 Hz, H-2 ), 5.45 (d, 1H,
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
J = 2.29, H-1 ),5.51 (d, 1H, J = 2.73, H-3), 5.82 (s, 2H, NH2), 6.80–7.60
(m, 6H, Harom). Anal. For C30H36N6O13 Calcd.: C, 52.32; H, 5.27; N, 12.20.
Found: C, 52.06; H, 5.13; N, 11.87.
Acetic acid 2,3-diacetoxy-1-acetoxymethyl-4-(acetyl-{4-amino-6-[2-(4-
methoxyphenyl)vinyl]-5-oxo-4,5-dihydro-[1,2,4]triazin-3-yl}hydrazono)butyl
ester (19d). (70%); m.p. 247–249◦C; MS: m/z 616 (M+, 2.30); IR (KBr),
1
1614 (CN), 1670 (C = ON), 1746 (C = OO) cm−1; H NMR (DMSO-d6)
δ 1.79–2.23 (m, 12H, 4CH3CO, 4Ac), 2.51 (s, 3H, NCOCH3), 3.68 (s, 3H,
CH3O-4), 3.45 (s, 2H, NH2), 4.91 (m, 1H, J = 5.73, H-5ꢁ), 5.22 (d, 1H, J =
3.18 Hz, H-4ꢁ), 5.81 (d, 1H, J = 4.54 Hz H-3ꢁ), 6.17 (s, 2H, H-1ꢁ, 2ꢁ), 6.22
(d, 1H, J = 3.33, H-3), 6.92–7.61 (m, 6H, Harom). Anal. For C27H32N6O11
Calcd.: C, 52.60; H, 5.23; N, 13.63. Found: C, 52.49; H, 5.27; N, 13.61.
Condensation of Compound 2 with Aldehydes: Formation of 20a–f
A mixture of compound 2 (2.74 g, 0.01 mol) and some aro-
matic aldehydes, namely: benzaldehyde, 4-methoxybenzaldehyde, 4-
hydroxybenzaldehyde, 2-nitrobenzaldehyde, thiophene-2-carboxaldehydem
and/or pyridine-2-carboxaldehyde (0.01 mol) was refluxed in methanol (40
ml) for 2 hr (TLC) and cooled to room temperature the precipitated solid
was filtered off, washed with ethanol and recrystallized from DMF/water
mixture to afford compounds 20a–f, respectively.
4-Amino-3-(Nꢁ-benzylidenehydrazino)-6-[2-(4-methoxyphenyl)vinyl]-4H-
[1,2,4] triazin-5-one (20a taut i). (89%), m.p. 230–233◦C, IR (KBr), 1586
1
(CN), 2967 (CH), 3238 (NH2), 3482 (NH) cm−1; H NMR (CDCl3): 3.81
(s, 3H, CH3O-4), 5.42 (s, 2H, NH2), 6.81 (d, 1H, J = 2.78 Hz, CH-NH,
tautomer ii), 7.32 (s, 1H, NH), 7.40–7.82 (m, 9H, Harom), 8.4 (s, 1H, HN-N =
C), 10.40 (s, 1H, CH = N). Anal. For C19H18N6O2 Calcd.: C, 62.97; H, 5.01;
N, 23.19. Found: C, 62.83; H, 4.97; N, 23.27.
4-Amino-3-[Nꢁ-(4-methoxybenzylidene)hydrazino]-6-[2-(4-methoxyph-
enyl)vinyl]-4H-[1,2,4]triazin-5-one (20b taut i). (98%), m.p. 240–241◦C, IR
1
(KBr), 1602 (CN), 2927 (CH), 3401 (NH) cm−1; H NMR (CDCl3): δ 3.81
(s, 6H, 2CH3O-4), 5.40 (s, 2H, NH2), 7.00 (m, 5H, Harom), 7.12 (d, 1H, J =
2.59 Hz, CH-NH, tautomer ii), 7.50–7.93 (m, 6H, Harom), 8.43 (s, 1H, HN-N
= C), 10.22 (s, 1H, CH = N). Anal. For C20H20N6O3 Calcd.: C, 61.22; H,
5.14; N, 21.42. Found: C, 61.07; H, 5.11; N, 21.39.

70
A. A. El-Barbary et al.
4-Amino-3-[Nꢁ-(4-hydroxybenzylidene)hydrazino]-6-[2-(4-methoxyph-
enyl)vinyl]-4H-[1,2,4]triazin-5-one (20c taut i). (94%), m.p. 262–264◦C,
1
IR (KBr), 1595 (CN), 2931 (CH), 3316 (NH) cm−1; H NMR (CDCl3):
3.82 (s, 6H, 2CH3O-4), 4.38 (s, 1H, OH), 5.73 (s, 2H, NH2), 6.88–7.38
(m, 4H, Harom), 7.50 (d, 1H, J = 2.49 Hz, CH-NH, tautomer ii), 7.18–7.99
(m, 6H, Harom), 8.81 (s,1H,HN-N = C), 10.22 (s, 1H, CH = N). Anal. For
C19H18N6O3 Calcd.: C, 60.31; H, 4.79; N, 22.21. Found: C, 60.19; H, 4.58;
N, 22.18.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-[Nꢁ-(2-nitrobenzylidene)
hydrazino]-4H-[1,2,4]triazin-5-one (20d taut i). (90%), m.p. 283–285◦C, IR
1
(KBr), 1612 (CN), 1343 (NO2), 3424 (NH) cm−1; H NMR (CDCl3): 3.84
(s, 3H, CH3O-4), 5.51 (s, 2H, NH2), 6.96 (m, 4H, Harom), 7.13 (d, 1H, J =
2.33 Hz, CH-NH, tautomer ii), 7.53–8.22 (m, 6H, Harom), 8.83 (s, 1H, HN-N
= C), 10.21 (s, 1H, CH = N). Anal. For C19H17N7O4 Calcd.: C, 56.02; H,
4.21; N, 24.07. Found: C, 55.58; H, 4.01; N, 24.64.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-(Nꢁ-thiophen-2-ylmethylene-
hydrazino)-4H-[1,2,4]triazin-5-one (20e taut i). (93%), m.p. 255–256◦C, IR
1
(KBr), 1601 (CN), 3085 (Ph), 3309 (NH2), 3444 (NH) cm−1; H NMR
(CDCl3): 3.22 (s, 3H, CH3O-4), 5.71 (s, 2H, NH2), 6.90 (d, 1H, J = 2.81 Hz,
CH-NH, tautomer ii), 7.2 (m, 5H, Harom), 7.51–7.80(m, 6H, Harom), 8.8 (s,
1H, HN-N = C), 10.32 (s, 1H, CH = N). Anal. For C17H16N6O2S Calcd.: C,
55.42; H, 4.38; N, 22.81. Found: C, 55.19; H, 4.27; N, 22.93.
4-Amino-6-[2-(4-methoxyphenyl)vinyl]-3-(Nꢁ-pyridin-2-ylmethylenehy-
drazino)-4H-[1,2,4]triazin-5-one (20f taut i). (93%), m.p. 242–243◦C, IR
1
(KBr), 1606 (CN), 3055 (Ph), 3213 (NH2), 3400 (NH) cm−1; H NMR
(CDCl3): 3.73 (s, 3H, CH3O-4), 5.59 (s, 2H, NH2), 6.81–7.23 (m, 4H,
Harom), 7.44(d, 1H, J = 2.79 Hz, CH-NH, tautomer ii), 7.88 (m, 6H, Harom),
8.43 (s, 1H, HN-N = C), 10.43 (s, 1H, CH = N). Anal. For C18H17N7O2
Calcd.: C, 59.50; H, 4.72; N, 26.98. Found: C, 59.35; H, 4.69; N, 26.87.
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Glycosylation of Some 6-Substituted-1,2,4-triazines
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