Synthesis of some new 2-α-L-arabinopyranosyl-1,2,4-triazines as potential antitumor chemotherapeutics

Article abstract of DOI:10.1081/NCN-120023274

Synthetic routes towards different 2-α -L-arabinopyranosyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5 4H)-/ones or thiones were investigated. Primary human anticancer screening of two selected compounds resulted in an active compound against SF-268 (CNS) cell line.

Full text of DOI:10.1081/NCN-120023274

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Synthesis of Some New 2-α-L-Arabinopyranosyl-1,2,4-
triazines as Potential Antitumor Chemotherapeutics
Abdel Kader Mansour a c , Mohga M. Eid a & Nasser S. A. M. Khalil b
a Department of Chemistry , Faculty of Science , Cairo University , Giza, Egypt
b Central Laboratory for Food and Feed , Agricultural Research Center , Giza, Egypt
c Department of Chemistry , Faculty of Science , Cairo University , Giza, Egypt
Published online: 07 Feb 2007.
To cite this article: Abdel Kader Mansour , Mohga M. Eid & Nasser S. A. M. Khalil (2003) Synthesis of Some New 2-α-L-
Arabinopyranosyl-1,2,4-triazines as Potential Antitumor Chemotherapeutics, Nucleosides, Nucleotides and Nucleic Acids, 22:9,
1805-1823, DOI: 10.1081/NCN-120023274
To link to this article: http://dx.doi.org/10.1081/NCN-120023274
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, No. 9, pp. 1805–1823, 2003
Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-
triazines as Potential Antitumor Chemotherapeutics
1
Abdel Kader Mansour,1, Mohga M. Eid,
*
and Nasser S. A. M. Khalil2
1Department of Chemistry, Faculty of Science,
Cairo University, Giza, Egypt
2Central Laboratory for Food and Feed,
Agricultural Research Center,
Giza, Egypt
ABSTRACT
Synthetic routes towards different 2-a-l-arabinopyranosyl-3-thioxo-2,3-dihydro-
1,2,4-triazin-5(4H)-=ones or thiones were investigated. Primary human anticancer
screening of two selected compounds resulted in an active compound against
SF-268 (CNS) cell line.
Key Words: Synthesis; 1,2,4-Triazines; a-l-Arabinopyranosyls; Antitumors.
INTRODUCTION
Many 1,2,4-triazine glycosides were reported to have pronounced biological
activity.[1] Only little attention had been directed towards the synthesis of unnatural
l-nucleosides until the finding that some b-l-nucleosides[2–5] were found to be more
active and less toxic than their d-isomers[5,6] against HIV-1 and Hepatitis B virus
*Correspondence: Abdel Kader Mansour, Department of Chemistry, Faculty of Science,
Cairo University, Giza, Egypt.
1805
DOI: 10.1081/NCN-120023274
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

1806
Mansour, Eid, and Khalil
(HBV).[7,8] Biochemically, some l-nucleosides are substrates for cellular kinases[9,10]
and also have greater stability for catabolizing enzymes such as cytidine and adeno-
sine deaminase,[11] thereby providing higher anti HIV and anti HBV activities.[2]
Recently, we have synthesized many 1,2,4-triazine galactosides[1] in order to find
new antitumor agents. In this context we found that 2-(2,3,4,6-tetra-O-acetyl-b-d-
galactopyranosyl)-6-benzyl-1,2,4-triazin-3,5(2H,4H)-dithione (1) showed a primary
an in vitro activity against both MCF7 (Breast) and SF-268 (CNS) cell lines. In con-
tinuation of our studies, it was of interest to synthesize some new a-l-arabinopyra-
nosides as promising antitumor chemotherapeutics. Therefore, herein we wish to
report the synthesis of some new 2-a-l-arabinosyl derivaties of 3-thioxo-2,3-dihy-
dro-1,2,4-triazin-5(4H)-=ones or thiones and the primary human anticancer screen-
ing of two selected nucleosides.
RESULTS AND DISCUSSION
Base induced glycosidation[1,12–17]of 4-amino-3-thioxo-2,3-dihydro-1,2,4-triazin-
5(4H)-ones followed by deamination was reported to offer a convenient selective
synthesis of the 2-glycosyl derivatives. [1,14–16] Also, glycosidation of the 4-aryl-3-
thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-ones was reported to give the corresponding
2-glycosyl derivatives.[1,17] In the present report we applied these strategies to selec-
tively synthesize some new 2-a-l-arabinopyranosyl-6-substituted-3-thioxo-2,3-
dihydro-1,2,4-triazin-5(4H)-ones.
Glycosidation of the 4-amino-6-substituted-3-thioxo-2,3-dihydro-1,2,4-tri-
azin-5(4H)-ones 4a-g with 2,3,4-tri-O-acetyl-b-l-arabinopyranosyl bromide (5) in
acetonitrile containing triethylamine gave the corresponding 4-amino-2-(2,3,4-tri-
O-acetyl-a-l-arabinopyranosyl)-6-substituted-3-thioxo-2,3-dihydro-1,2,4-triazin-
5(4H)-ones6a-g. Among the different possible monoarabinosyl derivatives 6–8, the
structure of 6a-g is clearly assigned by spectral and chemical evidences. Thus, the
position of the anomeric proton at d 6.82–6.67 with a coupling constant value of
8.7–9.4 Hz proves that the anomeric proton is in a trans position with respect to

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1807
the proton on position 2 of the l-arabinosyl ring which comes in agreement to the a-
N-arabinopyranosyls 6a-g and not their isomeric a-S-derivatives (this is consistent
with reported positions and coupling constant values of the anomeric protons of
N-type of different pyranosyls).[1,13,14,16,17] The presence of the NH2 protons signal
of d 6.51–6.32 excludes the formation of the a-4-NH-pyranosyls 8a-g.
Analogous arabinopyrnosylation of the 4-aryl-6-substituted-3-thioxo-2,3-dihy-
dro-1,2,4-triazin-5(4H)-ones 10a-i gave the corresponding 4-aryl-2-(2,3,4-tri-O-
acetyl-a-l-arabinopyranosyl)-6-substituted-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-
ones (11a-i). Assignment of the structure of compounds 11a-i rather than their
isomeric S-arabinopyranosyl derivatives 12a-i was established spectroscopically.
1
Thus, the HNMR spectral data of compounds 11a-i revealed the position of the
0
0
anomeric protons at d 6.78–6.69 (JH-1 -H-2 ¼ 8.4–9.4 Hz) in agreement with that
reported for analogous 4-aryl-2-(2,3,4,6-tetra-O-acetyl-b-d-gluco[14,17]=or galactopyr-
anosyl[1])-6-substituted-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-ones.
Deamination of 6d-g into the target compounds 13a-d was achieved in almost
quantitative yields by the action of nitrous acid in acetic acid. The structure of com-
1
pounds 13a-d was inferred from their chemical and spectral evidences. Thus, the H
NMR spectra of compounds 13a-d showed the absence of NH2 signal at d 6.51–6.32
and appearance of NH signal at d 10.76–9.32 (brs, 1H, exchangeable). Thiation of
the latter compounds with phosphorous pentasulphide in pyridine afforded the cor-
responding 2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-substituted-1,2,4-triazine-
3,5(2H, 4H)-dithiones 14a-d. Structure assignment of compounds 14a-d was inferred
from their correct analytical and spectral data. Thus, the IR spectra of these com-
pounds showed the absence of the amide carbonyl function at 1716–1713 cmꢀ1. Also,
1
the H NMR spectra of compounds 14a-d revealed signals consistent with their
structures.
Condensation of compounds 6d-g with different aldehydes gave the correspon-
ding 4-arylideneamino derivatives 15a-k. The structure of 15a-k was inferred from
1
their analytical, chemical, and spectral data. Thus, the H NMR spectra of these
compounds revealed N¼CH signal at d 8.72–8.13 consistent with similar reported
data.[1,14–16]
Heating of compound 15b under reflux for 30 minutes with benzaldehyde
afforded compound 13b via the elimination of benzonitrile.
Treatment of the appropriate acetyl derivatives 6f, 13a-d with methanolic
ammonia led to the formation of the corresponding free l-arabinopyranosyl nucleo-
sides 16, 17a-d respectively.
BIOLOGICAL EVALUATION
Compounds 6g, and 15j were tested for their human anticancer activity using an
in vitro model through a 3-cell line, one-dose primary anticancer assay consisting of
MCF7 (Breast), NCI-H460 (Lung), SF-268 (CNS). Only compound 15j was found to
be active against SF-268 (CNS) in this 3-cell line one dose primary human anti-
cancer assay. The following table shows the activity of the previously mentioned
compounds.

1808
Mansour, Eid, and Khalil
Table 1. Human anticancer activity of compounds 6g, 15j.
Growth Percentage
(Lung)
NCI-H460
(Breast)
MCF7
(CNS)
SF-268
Compound
Concentration
Activity
6g
15j
1.00 E–0.04 M
1.00 E–0.04 M
67
69
71
52
48
ꢀ28
Inactive
Active
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded on a Perkin-
1
Elmner 1430 spectrophotometer. H NMR spectra were recorded at 200 MHz with
a Varian GEMINI 2000 spectrometer. Element analyses were carried out at the
microanalytical Center, Cairo University. Anticancer screening of compounds 6g,
15j was carried out at the National Cancer Institute – National Institutes of Health,
Bethesda, Maryland, United States of America. The starting 4-amino=4-aryl-6-
substituted-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-ones 4a-g[18–20]=10a-i,[1,21] and
2,3,4-tri-O-acetyl-b-l-arabinopyranosyl bromide (5)[22] were prepared as reported.
4-Amino-2-(2,3,4-tri-O-acetyl-a-l-arbinopyranosyl)-6-substituted-3-thioxo-2,3-
dihydro-1,2,4-triazin-5(4H)-ones (6a-g). General Procedure: 2,3,4-tri-O-acetyl-b-l-
arabinopyranosyl bromide (5) (10 mmol) was added to a solution of each of
compounds 4a-g (10 mmol) in acetonitrile (5 mL) and triethylamine (2 mL, 14 mmol).
After shaking the reaction mixture for 20 minutes, it was left overnight at room tem-
perature. The next day, the reaction mixture was cooled in an ice bath, acidified with
acetic acid (1 mL) and diluted with cold water. The precipitate was then collected by
filtration, dried at room temperature, and recrystallized from dichloromethane=
petroleum ether (bp. 40–60ꢁC) as brown crystals of compounds 6a-c or from dichloro-
methane=methanol as yellow crystals of compounds 6d-g.
4-Amino-2-(2,3,4-tri-O-acetyl-a-l-arbinopyranosyl)-6-phenyl-3-thioxo-2,3-dihydro-
1,2,4-triazin-5(4H)-one (6a). Using the general procedure, 4a gave 6a (46%); mp.
132ꢁC; IR (KBr) 3294, 3209 (NH2), 1747 (C¼O acetate), 1689 (C¼O amide) cmꢀ1
;
1H NMR (CDCl3) d 8.2–7.44 (m, 5H, ArH’), 6.82 (d, 1H, JH-1 -H-2 ¼ 9 Hz, H-1 ), 6.51
0
0
0
0
0
0
0
(s, 2H, NH2, exchangeable), 6.08 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.5 Hz, H-2 ),
5.4 (d, 1H, JH-4 -H-3 ) ¼ 3.4 Hz, H-40), 5.3 (dd, 1H, JH-3 -H-4 ) ¼ 3.4 Hz, JH-3 -H-2 ¼ 10 Hz,
0
0
0
0
0
0
H-30), 4.16 (dd, 1H, JH-5 -H-4 ¼ 1.9 Hz, JH-5 -H-5 ¼ 13.5 Hz, H-5 ), 3.94 (d, 1H,
0
0
0
0
00
00
00
0
JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 2.19, 2.06, 1.98 (3s, 9H, CH3CO).
Anal. Calcd. for C20H22N4O8S: C, 50.2; H, 4.63; N, 11.71. Found; C, 50.2; H,
4.7; N, 12.0.
4-Amino-2-(2,3,4-tri-O-acetyl-a-l-arbinopyranosyl)-6-benzyl-3-thioxo-2,3-dihydro-
1,2,4-triazin-5(4H)-one (6b). Using the general procedure, 4b gave 6b (62%); mp.
110ꢁC; IR (KBr) 3308, 3215 (NH2), 1747 (C¼O acetate), 1689 (C¼O amide) cmꢀ1
;
1H NMR (CDCl3) d 7.42–7.2 (m, 5H, ArH’s), 6.67 (d, 1H, JH-1 -H-2 ¼ 9.2 Hz, H-1 ),
0
0
0

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1809
Scheme 1.

1810
Mansour, Eid, and Khalil
Scheme 2.

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1811
0
0
0
0
6.32 (s, 2H, NH2, exchangeable), 6.01 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2¼ 9.6Hz, H-2 ),
0
0
0
0
0
0
0
5.38 (d, 1H, JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.25 (dd, 1H, JH-3 -H-4 ¼ 3.6 Hz, JH-3 -H-2
¼
10 Hz, H-30), 4.13 (dd, 1H, JH-5 -H-4 ¼ 1.9 Hz, JH-5 -H-5 ¼ 13.5 Hz, H-5 ), 4.14–3.85
0
0
0
0
00
00
00
0
(m, 2H, PhCH2), 3.95 (d, 1H, JH-5 -H-5 ¼ 13.6 Hz, H-5 ), 2.22, 2.05, 1.91 (3s,
9H, CH3CO).
Anal. Calcd. for C21H24N4O8S Calcd.: C, 51.21; H, 4.91 Found: C, 51.3; H, 4.9.
4-Amino-2-(2,3,4-tri-O-acetyl-a-l-arbinopyranosyl)-6-(4-chlorobenzyl)-3-thioxo-2,3-
dihydro-1,2,4-triazin-5(4H)-one (6c). Using the general procedure, 4c gave 6c
(68%); mp. 88ꢁC; IR (KBr) 3113, 3219 (NH2), 1749 (C¼O acetate), 1693 (C¼O
1
amide)cmꢀ1; H NMR (CDCl3) d 7.36–7.26 (2d, 4H, ArH’s), 6.67 (d, 1H, JH-1 -H-2
¼
0
0
9.4 Hz, H-10), 6.33 (s, 2H, NH2, exchangeable), 5.94 (t, 1H, J¼ (JH-2 -H-1 þ JH-2 -H-3 )=
0
0
0
2 ¼ 9.5 Hz, H-20), 5.4 (d, 1H, JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.25 (dd, 1H, JH-3 -H-4
¼
¼
0
0
0
0
0
0
0
0
0
0
0
00
3.4 Hz, JH-3 -H-2 ¼ 10.0 Hz, H-3 ), 4.14 (dd, 1H, JH-5 -H-4 ¼ 1.7 Hz, JH-5 -H-5
13.2 Hz, H-50), 4.1–3.87 (m, 2H, 4-ClC6H4CH2), 3.9 (d, 1H, JH-5 -H-5 ¼ 13.4 Hz,
00
0
H-500), 2.2, 2.05, 1.92 (3s, 9H, CH3CHO).
Anal. Calcd. for C21H23N4O8SCL: C, 47.87; H, 4.4. Found: C, 47.9; H, 4.5.
4-Amino-2-(2,3,4-tri-O-acetyl-a-l-arbinopyranosyl)-6-styryl-3-thioxo-2,3-dihydro-
1,2,4-triazin-5(4H)-one (6d). Using the general procedure, 4d gave 6d (64%); mp.
180ꢁC; IR (KBr) 3302, 3202 (NH2), 1747 (C¼O acetate), 1680 (C¼O amide)
1
cmꢀ1; H NMR (CDCl3) d 8.04, 7.16 (2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.65–
0
0
0
7.36 (m, 5H, ArH’s), 6.69 (d, 1H, JH-1 -H-2 ¼ 9.2 Hz, H-1 ) 6.40 (s, 2H, NH2,
0
0
0
0
exchangeable), 6.05 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ), 5.42 (d, 1H,
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.6 Hz, JH-3 -H-2 ¼ 10.2 Hz, H-3 ),
0
0
0
0
00
00
0
4.18 (dd, 1H, JH-5 -H-4 ¼ 1.8 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.94 (d, 1H, JH-5 -H-5
¼
13.4 Hz, H-500), 2.25, 2.06, 1.92 (3s, 9H, CH3CO).
Anal. Calcd. for C22H24N4O8S: C, 52.37; H, 4.79. Found: C, 52.4; H, 4.8.
4-Amino-2-(2,3,-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-4-methylphenyl)vinyl-3-
thioxo-2,3-dihydro-1,2,4,-triazin-5(4H)-one (6e). Using the general procedure, 4e
gave 6e (77.0%); mp. 178ꢁC; IR (KBr) 3306, 3209 (NH2), 1747 (C¼O acetate),
1
1686 (C¼O amide) cmꢀ1; H NMR (CDCl3) d 8.0, 7.11 (2d, 2H, J ¼ 16.3 HZ, trans
0
0
0
CH¼CH), 7.51, 7.2 (2d, 4H, ArH’s), 6.68 (d, 1H, JH-1 -H-2 ¼ 8.7 Hz, H-1 ), 6.43 (s,
0
0
0
0
2H, NH2,exchangeable), 6.05 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.3 Hz, H-2 ),
4
0
0
0
0
0
0
5.41 (d, 1H, JH-4 -H-3 ¼ 3.4 Hz, H ), 5.27 (dd, 1H, JH-3 -H-4 ¼ 3.4 Hz, JH-3 -H-2
¼
10.0 Hz, H-30), 4.16 (dd, 1H, JH-5 -H-4 ¼ 1.8 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.94 (d,
0
0
0
0
00
00
00
0
1H, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 23.8 (s, 3H, CH3), 2.24, 2.05, 1.95 (3s, 9H, CH3CO).
Anal. Calcd. for C23H26N4O8S: C, 53.27; H, 5.05. Found: C, 53.3; H, 5.0.
4-Amino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-methoxyphenyl)vinyl-
3-thioxo-2,3-dihydro-1,2,4,-triazin-5(4H)-one (6f). Using the general procedure, 4f
gave 6f (74%); mp. 212ꢁC; IR (KBr) 3308, 3209 (NH2), 1747 (C¼O acetate), 1691
(C¼O amide) cmꢀ1
;
1H NMR (CDCl3) d 7.98, 7.03 (2d, 2H, J ¼ 16.4 Hz, trans
CH¼CH), 7.57, 6.92 (2d, 4H, ArH’s), 6.42 (s, 2H, NH2, exchangeable), 6.68 (d,
0
0
0
0
0
0
0
1H, JH-1 -H-2 ¼ 9.2 Hz, H-1 ), 6.06 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.7 Hz, H-2 ),
0
0
0
0
0
0
0
5.41 (d, 1H, JH-4 -H-3 ¼ 3.6 Hz, H-4 ), 5.27 (dd, 1H, JH-3 -H-4 ¼ 3.6 Hz, JH-3 -H-4 ¼ 3.6 Hz,

1812
Mansour, Eid, and Khalil
0
0
0
0
0
0
0
00
JH-3 H-2 ¼ 10.0 Hz, H-3 ), 4.17 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 14 Hz, H-5 ),
00
00
0
3.94 (d, 1H, JH-5 -H-5 ¼ 14 Hz, H-5 ), 3.85 (s, 3H, OCH3), 2.24, 2.05, 1.95 (3s, 9H,
CH3CO).
Anal. Calcd. for C23H26N4O9S: C, 51.68; H, 4.9. Found: C, 51.7; H, 4.9.
4-Amino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(-4-chlorophenyl)vinyl-
3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (6g). Using the general procedure, 4g
gave 6g (76%); mp. 196ꢁC; IR (KBr) 3319, 3214 (NH2), 1749, 1728 (C¼O acetate),
1689 (C¼O amide) cmꢀ1; 1H NMR (CDCl3) d 7.98, 7.12 (2d, 2H, J ¼ 16.4 Hz, trans
0
0
0
CH¼CH), 7.37 (2d, 4H, ArH’s), 6.69 (d, 1H. JH-1 -H-2 ¼ 9.2 Hz, H-1 ), 6.45 (s,
0
0
0
0
2H,NH2, exchangeable), 6.05 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ),
0
0
0
0
0
0
0
5.42 (d, 1H, JH-4 -H-3 ¼ 3.5 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.5 Hz. JH-3 -H-2
¼
10.1 Hz,H-30),4.17(dd,1H,JH-5 -H-4 ¼ 1.6 Hz,JH-5 -H-5 ¼ 13.4 Hz,H-5 ),3.94(d,1H,
0
0
0
0
00
00
00
0
JH-5 -H-5 ¼ 13.2 Hz, H-5 ), 2.25, 2.06, 1.96 (3s, 9H, CH3CO).
Anal. Calcd. for C22H23N4O8SCl: C, 49.03; H, 4.3. Found: C, 49.0; H, 4.2.
4-Aryl-6-substituted-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl-6-substituted-3-
thioxo-2,3-dihydro-1,2,4,-triazin-5(4H)-ones (11a-i). General Procedure: To a solu-
tion of each of 10a-i (10 mmol) in acetonitrile (5 mL) and triethylamine (2 mL, 14
mmol) was added 2,3,4-tri-O-acetyl-b-l-arabino-pyranosyl bromide (5) (10 mmol).
After shaking the reaction mixture for 20 minutes it was kept at room temperature
overnight. The reaction mixture was then cooled, acidified with acetic acid (1 mL)
and the formed preciptate was collected by filtration, washed with ater, and dried
at room temperature. Compounds 11a-i were extracted from ethyl acetate and pur-
ified by preparative TLC plates (silica gel 60 GF254) using ethyl acetate as an eluent.
The eluted compounds were then extracted from chloroform on a soxhlet extractor.
The chloroform extracts were concentrated and diluted with petroleum ether (bp.
40–60ꢁC). After collection of crude 11a-i by filtration, they were recrystallized from
diethylether=petroleum ether (bp. 40–60ꢁC). as pale crystals of 11a-g and orange
yellow crystals of 11h,i.
4-Phenyl-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-benzyl-3-thioxo-2,3-dihydro-
1,2,4,-triazin-5(4H)-one (11a). Using the general procedure, 10a gave 11a (55%);
1
Rf ¼ 0.72; mp. 104ꢁC; IR (KBr) 1747 (C¼O acetate), 1701 (C¼O amide) cmꢀ1; H
0
0
0
NMR (CDCl3) d 7.54–7.15 (m, 10H, ArH’s), 6.76 (d, 1H, JH-1 -H-2 ¼ 9.0 Hz, H-1 ),
0
0
0
0
0
0
6.01 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.3 Hz, H-2 ), 5.38 (d, 1H, JH-4 -H-3
¼
3.0 Hz, H-40), 5.26 (dd, 1H, JH-3 -H-4 ¼ 3.0 Hz, JH-3 -H-2 ¼ 9.0 Hz, H-3 ), 4.15(dd,
0
0
0
0
0
0
0
0
00
000
1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.2 Hz, H-5 ), 3.97 (s, 2H, PhCH2), 3.89 (d,
00
0
1H, JH-5 -H-5 ¼ 13.2 Hz, H-5 ), 2.23, 2.07, 2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C27H27N3O8S: C, 58.58; H, 4.91;N,7.59. Found: C, 58.6;
H, 5.0; N, 7.6.
4-(4-Methylphenyl)-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-benzyl-3-thioxo-
2,3-dihydro-1,2,4-triazin-5(4H)-one (11b). Using the general procedure, 10b gave
11b (68%); Rf ¼ 0.74; mp. 88ꢁC; IR (KBr) 1747 (C¼O acetate), 1701 (C¼O amide)
cmꢀ1; 1H NMR (CDCl3) d 7.45–6.98 (m, 9H, ArH’s), 6.78 (d, 1H, JH-1 -H-2 ¼ 9.2 Hz,
0
0
0
Hz, H-10), 6.02 (t, 1H, J ¼ (J
þ JH-2 -H-3 )=2 ¼ 9.1 Hz, H-2 ), 5.39 (d, 1H,
0
0
H-20-H-1

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1813
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.3 Hz, H-4 ), 5.26 (dd, 1H, JH-3 -H-4 ¼ 3.3 Hz, JH-3 -H-2 ¼ 9.8 Hz, H-3 ),
0
0
0
00
0 0
4.11 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.0 Hz, H-5 ), 3.98 (s, 2H, PhCH2),
00
0
3.88 (d, 1H, JH-5 -H-5 ¼ 13.0 Hz, H-5 ), 2.42 (s,3H,4-CH3-C6H4-N), 2.24, 2.08,2.00
(3s, 9H, CH3CO).
Anal. Calcd. for C28H29N3O8S: C, 59.25; H, 5.15. Found: C, 59.3; H, 5.2.
4-Phenyl-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-(-4-methylbenzyl)-3-thioxo-
2,3-dihydro-1,2,4,-triazin-5(4H)-one (11c). Using the general procedure, 10c gave
11c (82%); Rf ¼ 0.7; mp. 168ꢁC; IR (KBr) 1747 (C¼O acetate), 1709 (C¼O amide)
1
cmꢀ1; H NMR (CDCl3) d 7.2–7.07 (m, 9H, ArH’s), 6.74 (d, 1H, JH-1 -H-2 ¼ 8.6 Hz
0
0
H-10), 6.04 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 8.6 Hz, H-2 ), 5.41 (d, 1H, JH-4 -H-3
¼
0
0
0
0
0
0
3.0 Hz, H-40), 5.25(dd, 1H, JH-3 -H-4 ¼ 3.0 Hz, JH-3 -H-2 ¼ 9.7 Hz, H-3 ), 4.14(dd, 1H,
0
0
0
0
0
0
0
0
0
00
JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.0 Hz, H-5 ), 3.92 (s, 2H, 4-CH3C6H4CH2), 3.85
00
00
0
(d, 1H, JH-5 -H-5 ¼ 13.0 Hz, H-5 ), 2.32 (s, 3H, 4-CH3C6H4CH2), 2.22, 2.06, 1.99
(3s, 9H, CH3CO).
Anal. Calcd. for C28H29N3O8S: C, 59.25; H, 5.15. Found: C, 59.4; H, 5.1.
4-(4-Methylphenyl)-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-(4-methylben-
zyl)-3-thioxo-2,3-dihydro-1,2,4,-triazin-5(4H)-one (11d). Using the general proce-
dure, 10d gave 11d (78%); Rf ¼ 0.75; mp. 118ꢁC; IR (KBr) 1751 (C¼O acetate),
1
1701 (C¼O amide) cmꢀ1; H NMR (CDCl3) d 7.34–6.96 (m, 8H, ArH’s), 6.76 (d,
0
0
0
0
0
0
0
1H, JH-1 -H-2 ¼ 8.7 Hz, H-1 ), 6.03 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 8.7 Hz, H-2 ),
0
0
0
0
0
0
0
5.38 (d, 1H, JH-4 -H-3 ¼ 2.9 Hz, H-4 ), 5.25(dd, 1H, JH-3 -H-4 ¼ 2.9 Hz, JH-3 -H-2
¼
9.2 Hz, H-30), 4.16(dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 12.75 Hz, H-5 ), 3.93 (s,
0
0
0
0
00
00
00
0
2H, 4-CH3C6H4CH2), 3.85 (d, 1H, JH-5 -H-5 ¼ 12.7 Hz, H-5 ), 2.4 (s, 3H, 4-
CH3C6H4-N), 2.33, (s, 3H, 4-CH3C6H4CH2), 2.23, 2.07,2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C29H31N3O8S: C, 59.88; H, 5.37. Found: C, 60.0; H, 5.4.
4-Phenyl-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-(4-methoxybenzyl)-3-thioxo-
2,3-dihydro-1,2,4,-triazin-5(4H)-one (11e). Using the general procedure, 10e gave
11e (95%); Rf ¼ 0.73; mp. 138ꢁC; IR (KBr) 1747 (C¼O acetate), 1705 (C¼O amide)
cmꢀ1; 1H NMR (CDCl3) d 7.53–6.88 (m, 9H, ArH’s), 6.77 (d, 1H, JH-1 -H-2 ¼ 9.1 Hz,
0
0
0
H-10), 6.02 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.8 Hz, H-2 ), 5.38 (d, 1H, JH-4 -H-3
¼
0
0
0
0
0
3.2 Hz, H-40), 5.26 (dd, 1H, JH-3 -H-4 ¼ 3.2 Hz, JH-3 -H-2 ¼ 9.8 Hz, H-3 ), 4.13 (dd,
0
0
0
0
0
0
0
0
0
00
1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13 Hz, H-5 ), 3.91 (s, 2H, 4-CH3OC6H4CH2), 3.86
00
00
0
(d, 1H, JH-5 -H-5 ¼ 13.1 Hz, 5 ), 3.79 (s, 3H, 4-CH3OC6H4-CH2), 2.23, 2.07, 2.0 (3s,
9H, CH3CO).
Anal. Calcd. for C28H29N3O9S: C, 57.62; H, 5.01. Found: C, 57.6; H, 5.1.
4-(4-Methylphenyl)-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-(4-methoxybenzyl)-
3-thioxo-2,3-dihydro-1,2,4,-triazin-5(4H)-one (11f). Using the general procedure,
10f gave 11f (85%); Rf ¼ 0.71; mp. 90ꢁC; IR (KBr) 1747 (C¼O acetate), 1705
1
(C¼O amide) cmꢀ1; H NMR (CDCl3) d 7.35–6.85 (m, 8H, ArH’s), 6.75 (d, 1H,
0
0
0
0
0
0
0
JH-1 -H-2 ¼ 9.4 Hz, H-1 ), 6.01 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 ) =2 ¼ 9.4 Hz, H-2 ),
0
0
0
0
0
0
0
5.38 (d, 1H, JH-4 -H-3 ¼ 3.15 Hz, H-4 ), 5.25 (dd, 1H, JH-3 -H-4 ¼ 3.15 Hz, JH-3 -H-2
¼
9.4 Hz, H-30), 4.13 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.88 (s, 2H,
0
0
0
0
00

1814
Mansour, Eid, and Khalil
00
0
4-CH3OC6H4CH2), 3.77 (s, 3H, 4-CH3OC6H4CH2), 3.86 (d, 1H, JH-5 -H-5 ¼ 13.4 Hz,
H-500), 2.39 (s, 3H, 4-CH3C6H4N), 2.21, 2.07, 2.09 (3s, 9H, CH3CO).
Anal. Calcd. for C29H31N3O9S: C, 58.28; H, 5.23. Found: C, 58.3; H, 5.2.
4-Phenyl-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-(4-chlorobenzyl)-3-thioxo-
2,3-dihydro-1,2,4,-triazin-5(4H)-one (11g). Using the general procedure, 10g gave
11g (81.3%); Rf ¼ 0.73; mp. 104ꢁC; IR (KBr) 1751 (C¼O acetate), 1701 (C¼O amide)
cmꢀ1; 1H NMR (CDCl3) d 7.54–7.15 (m, 9H, ArH’s), 6.77 (d, 1H, JH-1 -H-2 ¼ 9.0 Hz,
0
0
0
H-10), 5.91 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.4 Hz, H-2 ), 5.38 (d, 1H, JH-4 -H-3
¼
0
0
0
0
0
3.4 Hz, H-40), 5.23 (dd, 1H, JH-3 -H-4 ¼ 3.4 Hz, JH-3 -H-2 ¼ 10.0 Hz, H-3 ), 4.13(dd,
0
0
0
0
0
0
0
0
0
00
1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.92 (s, 2H, 4-ClC6H4CH2),
00
00
0
3.84 (d, 1H, JH-5 -H-5 ¼ 13.5 Hz, H-5 ), 2.2, 2.06, 1.99 (3s, 9H, CH3CO).
Anal. Calcd. for C27H26N3O8SCl: C, 55.15; H, 4.46. Found: C, 55.2; H, 4.4.
4-Phenyl-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-(4-N,N-dimethylamino-
benzyl)-3-thioxo-2,3-dihydro-1,2,4,-triazin-5(4H)-one (11h). Using the general pro-
cedure, 10h gave 11h (60%); Rf ¼ 0.70; mp. 120ꢁC; IR (KBr) 1747 (C¼O acetate),
1
1701 (C¼O amide) cmꢀ1; H NMR (CDCl3) d 7.52–6.7 (m, 9H, ArH’s), 6.69 (d,
0
0
0
0
0
0
0
1H, JH-1 -H-2 ¼ 8.4 Hz, H-1 ), 6.04 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ),
0
0
0
0
0
0
0
5.48 (d, 1H, JH-4 -H-3 ¼ 3.6 Hz, H-4 ), 5.23 (dd, 1H, JH-3 -H-4 ¼ 3.0 Hz, JH-3 -H-2
¼
10.2 Hz, H-30), 4.19 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 12.6 Hz, H-5 ), 3.97 (d,
0
0
0
0
00
00
00
0
1H, JH-5 -H-5 ¼ 13.5 Hz, H-5 ), 3.86 (s, 2H, 4-NMe2C6H4CH2), 2.92 (s, 6H, 4-
N(CH3) -C6H4CH2),2.14–1.95 (3s, 9H, CH3CO).
2
Anal. Calcd. for C29H32N4O8S: C, 58.38; H, 5.40; N, 9.39. Found: C, 58.4; H,
5.4; N, 9.6.
4-(4-Methylphenyl-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-(4-N,N-dime-
thylaminobenzyl)-3-thioxo-2,3-dihydro-1,2,4,-triazin-5(4H)-one (11i). Using the gen-
eral procedure, 10i gave 11i (57.4%); Rf ¼ 0.75; mp. 100ꢁC; IR (KBr) 1747 (C¼O
1
acetate), 1701 (C¼O amide) cmꢀ1; H NMR (CDCl3) d 7.56–6.74 (m, 8H, ArH’s),
0
0
0
0
0
0
6.72 (d, 1H, JH-1 -H-2 ¼ 8.7 Hz, H-1 ), 6.01 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=
2 ¼ 9.6 Hz, H-20), 5.49 (d, 1H, JH-4 -H-3 ¼ 3.1 Hz, H-4 ), 5.23 (dd, 1H, JH-3 -H-4
¼
¼
0
0
0
0
0
0
0
0
0
0
0
00
3.3 Hz, JH-3 -H-2 ¼ 10.2 Hz, H-3 ), 4.17 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5
12.5 Hz, H-50), 3.94 (d, 1H, JH-5 -H-5 ¼ 13.5 Hz, H-500), 3.86 (s, 2H, 4-
NMe2C6H4CH2), 2.93 (s, 6H, 4-N(CH3)2C6H4CH2), 2.39 (s, 3H, 4-CH3-
C6H4N),2.14–1.95 (3s, 9H, CH3CO).
00
0
Anal. Calcd. for C30H34N4O8S: C, 59.0; H, 5.61. N, 9.17. Found: C, 5.9; H, 5.9;
N, 9.2.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-substituted-3-thioxo-2,3-dihydro-1,2,4,-
triazin-5(4H)-ones (13a-d). General procedure: To a solution of each of 6d-g
(10 mmol) in acetic acid (100 mL) was added a solution of sodium nitrite (6 g in
6 mL water) dropwise with stirring and cooling at 0ꢁC over a period of one hour
and the reaction mixture was then kept in the refrigerator overnight. The next day,
the reaction mixture was diluted with an ice-water mixture (400 g) and the formed
precipitate was collected by filtration and dried at room temperature. Crude 13a
was recrystallized first from diluted ethanol then from (1:1) diethyl ether=petroleum

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1815
petroleumether(bp.40–60ꢁC). Crude13b,dwererecrystallizedfromdichloromethane=
methanol, and crude 13c was recrystallized from methanol. All compounds were
isolated as yellow crystals of pure 13a-d.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-styryl-3-thioxo-2,3-dihydro-1,2,4,-
triazin-5(4H)-one (13a). Using the general procedure, 6d gave 13a (59%); mp.
1
176ꢁC; IR (KBr) 3230 (NH), 1749 (C¼O acetate), 1716 (C¼O amide) cmꢀ1; H
NMR (CDCl3) d 9.32 (brs, 1H, NH, exchangeable),7.91, 7.09 (2d, 2H, J ¼
0
0
16.3 Hz, trans CH¼CH), 7.58–7.35 (m, 5H, ArH’s), 6.63 (d, 1H, JH-1 -H-2
¼
0
9.3 Hz, H-10), 5.96 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.9 Hz, H-2 ), 5.4 (d, 1H,
0
0
0
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.24 (dd, 1H, JH-3 -H-4 ¼ 3.3 Hz, JH-3 -H-2 ¼ 9.3 Hz, H-3 ),
0
0
0
0
00
00
0
4.18 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.2 Hz, H-5 ), 3.92 (d, 1H, JH-5 -H-5
¼
13.2 Hz, H-500), 2.25, 2.05, 1.95 (3s, 9H, CH3CO).
Anal. Calcd. for C22H23N3O8S : C, 53.98; H, 4.73; N, 8.58. Found: C, 54.1; H,
4.7; N, 8.6.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-methylphenyl)vinyl-3-thioxo-2,3-
dihydro-1,2,4,-triazin-5(4H)-one (13b). Using the general procedure, 6e gave 13b (77%);
1
mp. 218ꢁC; IR (KBr) 3215 (NH), 1745 (C¼O acetate), 1715 (C¼O amide) cmꢀ1; H
NMR (CDCl3) d 10.2 (brs, 1H, NH, exchangeable), 8.0, 7.06 (2d, 2H, J ¼ 16.4 Hz, trans
0
0
0
CH¼CH), 7.49, 7.24 (2d, 4H, ArH’s), 6.64 (d, 1H, JH-1 -H-2 ¼ 9.2 Hz, H-1 ), 5.98 (t, 1H,
0
0
0
0
0
0
0
J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ), 5.42 (d, 1H, JH-4 -H-3 ¼ 3.2 Hz, H-4 ), 5.28
0
0
0
0
0
0
0
(dd, 1H, JH-3 -H-4 ¼ 3.5 Hz, JH-3 -H-2 ¼ 10.1 Hz, H-3 ), 4.19(dd, 1H, JH-5 -H-4
¼
0
0
0
00
00
0
1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.93 (d, 1H, JH-5 -H-5 ¼ 13.2 Hz, H-5 ), 2.37 (s, 3H,
CH3), 2.26, 2.06, 2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C23H25N3O8S: C, 54.86; H, 5.0. Found: C, 55.0; H, 5.0.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-methoxyphenyl)vinyl-3-thioxo-
2,3-dihydro-1,2,4,-triazin-5(4H)-one (13c). Using the general procedure, 6f gave 13c
(85.6%); mp. 138ꢁC; IR (KBr) 3212 (NH), 1749 (C¼O acetate), 1713 (C¼O amide)
cmꢀ1 1H NMR (CDCl3) d 10.76 (s, 1H, NH, exchangeable), 7.87, (2d, 2H,
;
0
0
J ¼ 16.4 Hz, trans CH¼CH), 7.52, 6.89 (2d, 4H, ArH’s), 6.62 (d, 1H, JH-1 -H-2
¼
0
9.4 Hz, H-10), 5.96 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ), 5.42 (d, 1H,
0
0
0
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.4 Hz, JH-3 -H-2 ¼ 10.1 Hz, H-3 ),
0
0
0
0
00
00
0
4.16 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.8 Hz, H-5 ), 3.92 (d, 1H, JH-5 -H-5
13.8 Hz, H-50), 3.84 (s, 3H, OCH3), 2.25, 2.06, 2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C23H25N3O9S: C, 53.17; H, 4.84. Found: C, 53.2; H, 4.8.
¼
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-chlorophenyl)vinyl-3-thioxo-2,3-
dihydro-1,2,4,-triazin-5(4H)-one (13d). Using the general procedure, 6g gave 13d
(75%); mp. 254ꢁC; IR (KBr) 3165 (NH), 1743 (C¼O acetate), 1713 (C¼O amide)
1
cmꢀ1; H NMR (CDCl3) d 9.75 (s, brs, 1H, NH, exchangeable), 7.99, 7.07 (2d,
0
0
2H, J ¼ 16.4 Hz, trans CH¼CH), 7.53, 7.37 (2d, 4H, ArH’s), 6.62 (d, 1H, JH-1 -H-2
¼
0
9.4 Hz, H-10), 5.96 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.5 Hz, H-2 ), 5.42 (d, 1H,
0
0
0
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.27 (dd, 1H, JH-3 -H-4 ¼ 3.6 Hz, JH-3 -H-2 ¼ 10.2 Hz, H-3 ),
0
0
0
0
00
00
0
4.19(dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.92 (d, 1H, JH-5 -H-5
¼
13.8 Hz, H-500), 2.25, 2.06, 2.0 (3s, 9H, CH3CO).

1816
Mansour, Eid, and Khalil
Anal. Calcd. for C22H22N3O8SCl: C, 50.43; H, 4.23;N,8.02. Found: C, 50.5;
H, 4.2;N,7.9.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-substituted-1,2,4-triazine-3,5 (2H,4H)-
dithiones (14a-d). General procedure: To a solution of each of 13a-d (1 mmol) in
dry pyridine (5 mL) was added phosphorous pentasulfide (0.45 g, 2 mmol). The reac-
tion mixture was then heated under reflux for 6 hours. After cooling, ethanol (10 mL)
was added, and the supernatent solution was decaned, acidified with acetic acid
(0.5 mL), concentrated, and diluted with water. The precipitate was collected by fil-
tration, dried at room temperature, dissolved in diethyl ether, and charcoal (0.5 g)
was added, filtered, and after evaporation of the ether, the residue obtained was
recrystallized from diethylether=petroleum ether (bp. 40–60ꢁC) as yellow crystals
of 14a-d.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-styryl-1,2,4-triazine-3,5(2H,4H)-di-
thione (14a). Using the general procedure, 13a gave 14a (51%); mp. 124ꢁC;
1
IR (KBr) 3209 (NH), 1749 (C¼O acetate) cmꢀ1; H NMR (CDCl3) d 8.04, 7.1
(2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.64–7.36 (m, 6H, NH, ArH’s), 6.7 (d, 1H,
0
0
0
0
0
0
0
0
JH-1 -H-2 ¼ 9.4 Hz, H-1 ), 6.1 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ), 5.42
0
0
0
0
0
0
0
(d, 1H, JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.4 Hz, JH-3 -H-2 ¼ 10 Hz,
H-30), 4.17 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.92 (d, 1H,
0
0
0
0
00
00
00
0
JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 2.26, 2.07, 2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C22H23N3O7S2: C, 52.27; H, 4.58;N,8.31. Found: C, 52.3; H,
4.5; N, 8.4.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-methylphenyl)vinyl-1,2,4-tri-
azine-3,5(2H,4H)-dithione (14b). Using the general procedure, 13b gave 14b (50%);
1
mp. 136ꢁC; IR (KBr) 3165 (NH), 1749 (C¼O acetate), cmꢀ1; H NMR (CDCl3) d
0
0
0
7.7–7.16 (m, 7H, NH, CH¼CH, ArH’s), 6.54 (d, 1H, JH-1 -H-2 ¼ 9.2 Hz, H-1 ),
0
0
0
0
0
0
0
6.05 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 ) =2 ¼ 9.8 Hz, H-2 ), 5.4 (d, 1H, JH-4 -H-3
¼
3.4 Hz, H-40), 5.23 (dd, 1H, JH-3 -H-4 ¼ 3.5 Hz, JH-3 -H-2 ¼ 10.1 Hz, H-3 ), 4.17 (dd,
0
0
0
0
0
0
0
0
0
0
0
00
1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.92 (d, 1H, JH-5 -H-5 ¼ 13.4 Hz,
H-500), 2.37 (s, 3H, CH3), 2.23, 2.07, 2.01 (3s, 9H, CH3CO).
Anal. Calcd. for C23H25N3O7S2: C, 53.17; H, 4.85. Found: C, 53.2; H, 4.8.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-methoxyphenyl)vinyl-1,2,4-tri-
azine-3,5(2H,4H)-dithione (14c). Using the general procedure, 13c gave 14c (52%);
1
mp. 142ꢁC; IR (KBr) 3200 (NH), 1749 (C¼O acetate), cmꢀ1; H NMR (CDCl3) d
0
0
0
7.64–6.88 (m, 7H, NH, CH¼CH, ArH’s),6.55 (d, 1H, JH-1 -H-2 ¼ 9.2 Hz, H-1 ), 6.09
0
0
0
0
0
0
0
(t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ), 5.42 (d, 1H, JH-4 -H-3 ¼ 3.4 Hz,
H-40), 5.23 (dd, 1H, JH-3 -H-4 ¼ 3.4 Hz, JH-3 -H-2 ¼ 10.1 Hz, H-3 ), 4.18 (dd, 1H,
0
0
0
0
0
0
00
0
0
0
00
00
0
JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.5 Hz, H-5 ), 3.93 (d, 1H, JH-5 -H-5 ¼ 13.4 Hz, H-5 ),
3.84 (s, 3H, OCH3), 2.23, 2.07, 2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C23H25N3O8S2: C, 51.58; H, 4.70. Found: C, 51.4; H, 4.8.
2-(2,3,4-Tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-chlorophenyl)vinyl-1,2,4-tri-
azine-3,5(2H,4H)-dithione (14d). Using the general procedure, 13d gave 14d (51%);

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1817
mp. 134ꢁC; IR (KBr) 3165 (NH), 1749 (C¼O acetate), cmꢀ1; 1H NMR (DMSO-d6) d
0
0
8.75 (brs, 1H, NH), 7.69–7.46 (m, 6H, CH¼CH, ArH’s), 6.72 (d, 1H, JH-1 -H-2
¼
0
9.2 Hz, H-10), 5.96 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ), 5.47 (d, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.3 Hz, JH-3 -H-2 ¼ 10.2 Hz, H-3 ),
0
0
0
0
00
0
0
4.08 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.6 Hz, H-5 ), 3.98 (d, 1H, JH-5 -H-5
¼
8.8 Hz, H-50), 2.16–1.92 (3s, 9H, CH3CO).
Anal. Calcd. for C22H22N3O7S2C1: C,48.93; H, 4.11. Found: C, 49.0; H, 4.1.
4-Arylideneamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-3-thioxo-2,3-dihy-
dro-1,2,4-triazin-5(4H)-ones (15a-k). General procedure: A mixure of each of 6d-g
(1 g) and the appropriate aldehyde (1 mL or 1 g) was heated at 150–160ꢁC in an oil
bath for 15 minutes. This mixure was then heated under reflux in methanol for further
30 minutes, cooled, and the product was collected by filtration. Compounds 15a-k
were recrystallized from methanol as yellow crystals.
4-Benzylidineamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-styryl-3-
thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15a). Using the general procedure, 6d
gave 15a (87%); mp. 208ꢁC; IR (KBr) 1743 (C¼O acetate), 1697 (C¼O amide)
1
cmꢀ1; H NMR (CDCl3) d 8.39 (s, 1H, N¼CH), 8.04, 7.19 (2d, 2H, J ¼ 16.4 Hz,
0
0
0
trans CH¼CH), 7.97–7.37 (m, 10 H, ArH’s),6.85 (d, 1H, JH-1 -H-2 ¼ 9 Hz, H-1 ),
0
0
0
0
0
0
0
6.09 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.8 Hz, H-2 ), 5.42 (d, 1H, JH-4 -H-3
¼
3.4 Hz, H-40), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.5 Hz, JH-3 -H-2 ¼ 10.1 Hz, H-3 ), 4.17 (dd,
0
0
0
0
0
0
0
0
0
00
00
0
1H, JH-5 -H-4 ¼ 1.8 Hz, JH-5 -H-5 ¼ 13 Hz, H-5 ), 3.94 (d, 1H, JH-5 -H-5 ¼ 13 Hz,
H-500), 2.26, 2.06, 2 0 (3s, 9H, CH3CO).
Anal. Calcd. for C29H28N4O8S: C,58.77; H, 4.76; N, 9.45. Found: C, 58.8; H,
4.6; N, 9.3.
4-Benzylidineamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-methylphenyl)
vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15b). Using the general proce-
dure, 6e gave 15b (78%); mp. 216ꢁC; IR (KBr) 1747 (C¼O acetate), 1693 (C¼O
amide) cmꢀ1
;
1H NMR (CDCl3) d 8.38 (s, 1H, N¼CH), 8.0, 7.14 (2d, 2H,
0
0
J ¼ 16.4 Hz, trans CH¼CH), 7.97–7.11 (m, 9H, ArH’s), 6.85 (d, 1H, JH-1 -H-2
¼
9.3 Hz, H-10), 6.09 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ), 5.41 (d, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.4 Hz, JH-3 -H-2 ¼ 10 Hz, H-3 ),
0
0
0
0
00
00
0
4.17 (dd, 1H, JH-5 -H-4 ¼ 1.8 Hz, JH-5 -H-5 ¼ 13.2 Hz, H-5 ), 3.94 (d, 1H, JH-5 -H-5
13.2 Hz, H-500), 2.37 (s, 3H, CH3), 2.26, 2.07, 2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C30H30N4O8S: C, 59.4; H, 4.98. Found: C, 59.4; H, 5.0.
¼
4-(4-Methylbenzylidineamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-
methylphenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15c). Using the
general procedure, 6e gave 15c (62%); mp. 238ꢁC; IR (KBr) 1743 (C¼O acetate),
1
1705 (C¼O amide), cmꢀ1; H NMR (CDCl3) d 8.32 (s, 1H, N¼CH), 8.01, 7.14
(2d, 2H, J ¼ 16.2 Hz, trans CH¼CH), 7.86–7.18 (m, 8H, ArH’s), 6.85 (d, 1H,
0
0
0
0
0
0
0
0
JH-1 -H-2 ¼ 9.2 Hz, H-1 ), 6.09 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ),
0
0
0
0
0
0
0 0
5.36 (d, 1H, JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.5 Hz, JH-3 -H-2
¼
10.1 Hz, H-30), 4.18 (dd, 1H, JH-5 -H-4 ¼ 1.5 Hz, JH-5 -H-5 ¼ 13.5 Hz, H-5 ), 3.94
0
0
0
0

1818
Mansour, Eid, and Khalil
00
00
0
(d, 1H, JH-5 -H-5 ¼ 13.2 Hz, H-5 ), 2.45 (s, 3H, 4-CH3-C6H4CH¼N), 2.38, (s, 3H,
4-CH3C6H4CH¼CH), 2.26, 2.07, 2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C31H32N4O8S: C, 59.99; H, 5.2. Found: C, 60.0; H, 5.2.
4-(4-Chlorobenzylideneamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-
methylphenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15d). Using the
general procedure, 6e gave 15d (72%); mp. 232ꢁC; IR (KBr) 1743 (C¼O acetate),
1
1697 (C¼O amide), cmꢀ1; H NMR (CDCl3) d 8.36 (s, 1H, N¼CH), 8.0, 7.13 (2d,
0
0
2H, J ¼ 16.4 Hz, trans CH¼CH), 7.91–7.18 (m, 8H, ArH’s), 6.83 (d, 1H, JH-1 -H-2
¼
0
9.2 Hz, H-10), 6.08 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.4 Hz, H-2 ), 5.41 (d, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.5 Hz, JH-3 -H-2 ¼ 10 Hz, H-3 ),
0
0
0
0
00
00
0
4.18 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.3 Hz, H-5 ), 3.93 (d, 1H, JH-5 -H-5
13.4 Hz, H-500), 2.38 (s, 3H, CH3), 2.25, 2.26, 1.99 (3s, 9H, CH3CO).
Anal. Calcd. for C30H29N4O8SCl: C, 56.2; H, 4.56. Found: C, 56.1; H, 4.6.
¼
4-(4-N,N-Dimethylaminobenzylideneamino-2-(2,3,4-tri-O-acetyl-a-l-arabino-
pyranosyl)-6-b-(4-methylphenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one
(15e). Using the general procedure, 6e gave 15e (80%); mp. 233ꢁC; IR (KBr)
1743 (C¼O acetate), 1697 (C¼O amide), cmꢀ1
;
1H NMR (CDCl3) d 8.13 (s,
1H, N¼CH), 8.01, 7.14 (2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.8–6.71 (m, 8H,
0
0
0
0
0
ArH’s), 6.87 (d, 1H, JH-1 -H-2 ¼9.0 Hz, H-1 ), 6.09 (t, 1H, J ¼ (JH-2 -H-1
þ
0
0
0
0
0
0
JH-2 -H-3 )=2 ¼ 9.5 Hz, H-2 ), 5.42 (d, 1H, JH-4 -H-3 ¼ 3.2 Hz, H-4 ), 5.28 (dd, 1H,
0
0
0
0
0
0 0
00 0
JH-3 -H-4 ¼ 3.5 Hz, JH-3 -H-2 ¼ 9.1 Hz, H-3 ), 4.18 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz,
0
0
00
0
JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.94 (d, 1H, JH-5 -H-5 ¼13.3 Hz, H-5 ), 3.1 (s, 6H,
N(CH3) ), 2.37, (s, 3H, 4-CH3C6H4CH¼CH), 2.25, 2.06, 1.98 (3s, 9H, CH3CO).
2
Anal. Calcd. for C32H35N5O8S: C, 59.16; H, 5.43;N, 10.78. Found: C, 59.2; H,
5.3;N, 10.8.
4-Benzylidineamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-methylphye-
nyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazine-5(4H)-one (15f). Using the general
procedure, 6f gave 15f (75%); mp. 223ꢁC; IR (KBr) 1751 (C¼O acetate), 1689
1
(C¼O amide), cmꢀ1; H NMR (CDCl3) d 8.38 (s, 1H, N¼CH), 7.99, 7.06 (2d,
0
0
2H, J ¼ 16.4 Hz, trans CH¼CH), 8.03–6.89 (m, 9H, ArH’s), 6.85 (d, 1H, JH-1 -H-2
¼
0
9.2 Hz, H-10), 6.09 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.7 Hz, H-2 ), 5.42 (d, 1H,
0
0
0
0
0
0
0
0
0
0
0
JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.5 Hz, JH-3 -H-2 ¼ 10.1 Hz, H-
30), 4.17 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.94 (d, 1H, JH-5 -H-5
13.6 Hz, H-500), 3.85 (s, 3H, OCH3), 2.26, 2.06, 2.0 (3s, 9H, CH3CO).
Anal. Calcd. for C30H30N4O9S: C, 57.87; H, 4.86; Found: C, 57.9; H,4.9.
¼
0
0
0
0
0
00
0
4-(4-Methylbenzylidineamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-
b-(4-methoxyphenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15g). Using
the general procedure, 6f gave 15g (69%); mp. 178ꢁC; IR (KBr) 1743 (C¼O acetate),
1
1697 (C¼O amide), cmꢀ1; H NMR (CDCl3) d 8.32 (s, 1H, N¼CH), 7.98, 7.05 (2d,
2H, J ¼ 16.4 Hz, trans CH¼CH), 7.85–6.89 (m, 8H, ArH’s), 6.85 (d, 1H,
0
0
0
0
0
0
0
0
JH-1 -H-2 ¼ 9.2 Hz, H-1 ), 6.09 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.6 Hz, H-2 ),
0
0
0
0
0
0
0 0
5.42 (d, 1H, JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.4 Hz, JH-3 -H-2
¼
10.2 Hz, H-30), 4.17 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.93
0
0
0
00

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1819
0
00
0
(d, 1H, JH-5 -H-5 ¼ 13.6 Hz, H-5 ), 3.84 (s, 3H, 4-CH3OC6H4CH¼CH), 2.44 (s, 3H,
4-CH3C6H4CH¼N), 2.25, 2.06, 1.99 (3s, 9H, CH3CO).
Anal. Calcd. for C31H32N4O9S: C, 58.48; H, 5.06; Found: C, 58.5; H, 5.0.
4-(4-Chlorobenzylidineamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-
methoxyphenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15h). Using the
general procedure, 6f gave 15h (75%); mp. 206ꢁC; IR (KBr) 1743 (C¼O acetate),
1
1697 (C¼O amide), cmꢀ1; H NMR (CDCl3) d 8.36 (s, 1H, N¼CH), 7.97, 7.04
(2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.91–6.89 (m, 8H, ArH’s), 6.83 (d, 1H,
0
0
0
0
0
0
0
0
JH-1 -H-2 ¼ 9.2 Hz, H-1 ), 6.08 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.4 Hz, H-2 ),
0
0
0
0
0
0
0
5.41 (d, 1H, JH-4 -H-3 ¼ 3 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.6 Hz, JH-3 -H-2
¼
10 Hz, H-30), 4.17 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.94 (d, 1H,
0
0
0
0
0
00
00
0
JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 3.84 (s, 3H, OCH3), 2.25, 2.06, 1.99 (3s, 9H, CH3CO).
Anal. Calcd. for C30H29N4O9SCl: C, 54.84; H, 4.45. Found: C, 55.0; H, 4.4.
4-(4-N,N-Dimethylaminobenzylidineamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-
6-b-(4-methoxyphenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15i). Using the
general procedure, 6f gave 15i (75%); mp. 229–230ꢁC; IR (KBr) 1743 (C¼O acet-
1
ate), 1697 (C¼O amide), cmꢀ1; H NMR (CDCl3) d 8.14 (s, 1H, N¼CH), 7.99,
7.06 (2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.82–6.86 (m, 8H, ArH’s), 6.73 (d,
0
0
0
0
0
0
0
0
1H, JH-1 -H-2 ¼ 8.8 Hz, H-1 ), 6.1 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.7 Hz, H-2 ),
0
0
0
0
0
0
0 0
5.42 (d, 1H, JH-4 -H-3 ¼ 3.4 Hz, H-4 ), 5.28 (dd, 1H, JH-3 -H-4 ¼ 3.5 Hz, JH-3 -H-2
¼
10.3 Hz, H-30), 4.18 (dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.6 Hz, H-5 ), 3.93
0
0
0
00
00
00
0
(d, 1H, JH-5 -H-5 ¼ 13.6 Hz, H-5 ), 3.85 (s, 3H, OCH3), 3.09 (s, 6H, N(CH3)2),
2.26, 2.06, 1.99 (3s, 9H, CH3CO).
Anal. Calcd. for C32H35N5O9S: C, 57.73; H, 5.3; N, 10.52. Found: C, 57.7; H,
5.2; N, 10.3.
4-Benzylidineamino-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-chlorophe-
nyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15j). Using the general pro-
cedure, 6g gave 15j (80%); mp. 240ꢁC; IR (KBr) 1747 (C¼O acetate), 1697 (C¼O
1
amide) cmꢀ1; H NMR (DMSO-d6) d 8.72 (s, 1H, N¼CH),7.83, 7.17 (2d, 2H, J ¼
0
0
16.4 Hz, trans CH¼CH), 7.99–7.51 (m, 9H, ArH’s), 6.86 (d, 1H, JH-1 -H-2 ¼ 9.2 Hz,
0
H-10), 5.91 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.7 Hz, H-2 ), 5.49 (dd, 1H, JH-3 -H-4
¼
0
0
0
0
0
0
0
0
0
0
0
0
3.6Hz, JH-3 -H-2 ¼ 10.3 Hz, H-3 ), 5.3 (d, 1H, JH-4 -H-3 ¼ 3.8 Hz, H-4 ), 4.17 (dd, 1H,
0
00
0
0
0
0
00
0
JH-5 -H-4 ¼ 1.5 Hz, JH-5 -H-5 ¼ 13.4 Hz, H-5 ), 4.0 (d, 1H, JH-5 -H-5 ¼ 13.2 Hz, H-5 ),
2.2, 1.99, 1.98 (3s, 9H, CH3CO).
Anal. Calcd. for C29H27N4O8SCl: C, 55.55; H, 4.34. Found: C, 55.5; H, 4.4.
4-(4-Methylbenzylidineamino)-2-(2,3,4-tri-O-acetyl-a-l-arabinopyranosyl)-6-b-(4-
chlorophenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (15k). Using the
general procedure, 6g gave 15k (80%); mp. 244ꢁC; IR (KBr) 1747 (C¼O acetate),
1
1697 (C¼O amide) cmꢀ1; H NMR (DMSO-d6) d 8.65 (s, 1H, N¼CH),7.83, 7.16
(2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.87–7.41 (m, 8H, ArH’s), 6.86 (d, 1H,
0
0
0
0
0
0
0
0
JH-1 -H-2 ¼ 9.2 Hz, H-1 ), 5.9 (t, 1H, J ¼ (JH-2 -H-1 þ JH-2 -H-3 )=2 ¼ 9.8 Hz, H-2 ), 5.48
0
0
0
0
0
0
0
(dd, 1H, JH-3 -H-4 ¼ 3.6 Hz, JH-3 -H-2 ¼ 10 Hz, H-3 ), 5.3 (d, 1H, JH-4 -H-3 ¼ 3.4 Hz,

1820
Mansour, Eid, and Khalil
00
H-40), 4.25(dd, 1H, JH-5 -H-4 ¼ 1.6 Hz, JH-5 -H-5 ¼ 13.6 Hz, H-5 ), 4.0 (d, 1H, JH-5 -H-5
13.6 Hz, H-50), 2.43 (s, 3H, CH3), 2.19, 1.99, 1.97 (3s, 9H, CH3CO).
Anal. Calcd. for C30H29N4O8SCl: C, 56.20; H, 4.56. Found: C, 56.2; H, 4.6.
¼
0
0
0
00
00
0
Synthesis of Compound 13b from Compound 15b. A mixture of 15b (1.6 mmol)
and benzaldehyde (1 mL) was heated under reflux for 30 minutes. After cooling and
washing with cold methanol, the remaining solid was collected by filtration and
recrystallized from methanol as yellow crystals of 13b (analytical and spectral data
of 13b were mentioned before).
Action of Methanolic Ammonia on 6f and 13a-d. General procedure: A satu-
rated methanolic ammonia solution (40 mol) (prepared by bubbing dry ammonia
gas in absolute methanol at 0ꢁC) was added to each of 6f, 13a-d (1 mmol). The reac-
tion mixture was then left overnight at room temperature in a stoppered flask (after
which time all materials went into solution). The solvent was then removed on rota-
vap at room temperature. Compounds 16, 17a-d were recrystallized from chloro-
form=ethanol as yellow crystals.
4-Amino-2-a-l-arabinopyranosyl-6-b-(4-methoxyphenyl)vinyl-3-thioxo-2,3-dihydro-
1,2,4-triazin-5(4H)-one (16). Using the general procedure, 6f gave 16 (75%); mp.
1
272ꢁC (decomp.); IR (KBr) 3500–3200 (OH, NH2), 1689 (C¼O amide) cmꢀ1; H
NMR (DMSO-d6) d 7.89, 7.03 (2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.66, 7.01
0
0
(2d, 4H, ArH’s), 6.76 (s, 2H, NH2, exchangeable), 6.25 (d, 1H, JH-1 -H-2 ¼ 8.8 Hz,
H-10), 5.09, 5.02, 4.8 (3d, 3H, 3OH, exchangeable), 4.3–3.17 (m, 5H, H-20, H-30,
H-40, H-50, H-500), 3.82 (s, 3H, OCH3).
Anal. Calcd. for C17H20N4O6S: C, 49.99; H, 4.93; N, 13.72. Found: C, 50.0; H,
4.9 N, 13.6.
2-a-l-Arabinopyranosyl-6-styryl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-one (17a). Using
the general procedure, 13a gave 17a (71%); mp. 120ꢁC (decomp.); IR (KBr) 3500–
1
3200 (OH, NH), 1701 (C¼O amide) cmꢀ1; H NMR (DMSO-d6) d 12.52 (brs, 1H,
NH, exchangeable), 7.8, 7.08 (2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.67, 7.4 (m,
0
0
0
5H, ArH’s), 6.22 (d, 1H, JH-1 -H-2 ¼ 8.8 Hz, H-1 ), 5.35, 5.07, 4.8 (3d, 3H, 3OH,
exchangeable), 4.3–3.29 (m, 5H, H-20, H-30, H-40, H-50, H-500).
Anal. Calcd. for C16H17N3O5S: C, 52.88; H, 4.71; N, 11.56. Found: C, 52.8; H,
4.8 N, 12.0.
2-a-l-Arabinopyranosyl-6-b-(4-methylphenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-tria-
zin-5(4H)-one (17b). Using the general procedure, 13b gave 17b (72%); mp. 130ꢁC
1
(decomp.); IR (KBr) 3500–3200 (OH, NH), 1701 (C¼O amide) cmꢀ1; H NMR
(DMSO-d6) d 8.27 (s, 1H, NH, exchangeable), 7.58, 7.03 (2d, 2H, J ¼ 16.4 Hz, trans
0
0
0
CH¼CH), 7.51, 7.22 (2d, 4H, ArH’s), 6.22 (d, 1H, JH-1 -H-2 ¼ 9 Hz, H-1 ), 5.34, 5.06,
4.8 (3d, 3H, 3OH, exchangeable), 4.3–3.0 (m, 5H, H-20, H-30, H-40, H-50, H-500). 2.33
(s, 3H, CH3).
Anal. Calcd. for C17H19N3O5S: C, 54.1; H, 5.07. Found: C, 54.1; H, 5.1.

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1821
2-a-l-Arabinopyranosyl-6-b-(4-methoxylphenyl)vinyl-3-thioxo-2,3-dihydro-
1,2,4-triazin-5(4H)-one (17c). Using the general procedure, 13c gave 17c (75%);
mp. 112ꢁC (decomp.); IR (KBr) 3500–3200 (OH, NH), 1697 (C¼O amide) cmꢀ1
;
1H NMR (DMSO-d6) d 8.38 (s, 1H, NH, exchangeable), 7.71, 6.99 (2d, 2H,
0
0
J ¼ 16.4 Hz, trans CH¼CH), 7.65, 7.03 (2d, 4H, ArH’s), 6.24 (d, 1H, JH-1 -H-2
¼
9.8 Hz, H-10), 5.36, 5.12, 4.82 (3d, 3H, 3OH, exchangeable), 4.3–3.3 (m, 5H, H-20,
H-30, H-40, H-50, H-500), 3.86 (s, 3H, OCH3).
Anal. Calcd. for C17H19N3O6S: C, 51.9; H, 4.87. Found: C, 52.0; H, 4.9.
2-a-l-Arabinopyranosyl-6-b-(4-chlorophenyl)vinyl-3-thioxo-2,3-dihydro-1,2,4-triazin-
5(4H)-one (17d). Using the general procedure, 13d gave 17d (73%); mp. 184ꢁC IR
1
(KBr) 3500–3200 (OH, NH), 1701 (C¼O amide) cmꢀ1; H NMR (DMSO-d6) d 8.3
(s, 1H, NH, exchangeable), 7.86, 7.05 (2d, 2H, J ¼ 16.4 Hz, trans CH¼CH), 7.67,
0
0
0
7.45 (2d, 4H, ArH’s), 6.19 (d, 1H, JH-1 -H-2 ¼ 8.7 Hz, H-1 ), 5.32, 5.02, 4.91 (3d, 3H,
3OH, exchangeable), 4.3–3.32 (m, 5H, H-20, H-30, H-40, H-50, H-500).
Anal. Calcd. for C16H16N3O5SCl: C, 48.3; H, 4.05. Found: C, 48.3; H, 4.1.
Biological Evaluation of Compounds (6g, 15j). An in vitro model was used as a
primary human anticancer screen of compounds 6g, 15j. A 3-cell line, one-dose assay
consisting of MCF 7 (Breast), NCI-H460 (Lung), SF-268 (CNS) was used for the
evaluation of the latter compounds. Each cell line was inoculated and preincubated
on a microtiter plate. Test agents were then added at a single concentration and the
culture were incubated for 48 hours. End point determination was made with sulfor-
hodamine B, a protein-binding dye. Results for each test agent were reported as the
percent of growth of the treated cells when compared to the untreated control cells.
Compounds which reduce the growth of any one of the cell lines to 32% or less
(negative number indicated cell kill) are active (Table 1).
ACKNOWLEDGMENTS
The authors are very grateful to Dr. V.L. Narayanan and Dr. Edward Sausvile,
National Cancer Institute=National Institutes of Health, Bethesda, Maryland,
U.S.A, for their valuable anticancer testing.
REFERENCES
1. Mansour, A.K.; Eid, M.M.; Khahil, N.S.A.M. Selective synthesis and reactions
of 6-substituted-2-b-galactosyl-1,2,4-triazines of potential anticancer activity.
Nucleosides, Nucleotides & Nucleic Acids 2003, 22 (1), 21–44.
2. Chang, C.N.; Doong, S.L.; Zhou, J.H.; Beach, J.W.; Jeong, L.S.; Chu, C.K.;
Tsai, C.H.; Cheng, Y.C. Deoxycytidine deaminase – resistant stereoisomer is
the active form of ( )-20,30-dideoxy-30-thiacytidine in the inhibitation of hepa-
titis B virus replication. J. Biol. Chem. 1992, 267, 13,938–13,942. Chem. Abstr.
1992, 117, 14,2910e.

1822
Mansour, Eid, and Khalil
3. Belleau, B.; Dixit, D.; Nguyen-Ba, N.; Kraus, J.L. Purinyl- and pyrimidinyl-
1,3-dioxolanes as anti-retrovirals. Eur. Pat. 337, 713, Oct 18, 1989. Chem.
Abstr. 1990, 112 198359w.
4. Furman, P.A.; Davis, M.; Liotta, D.C.; Paff, M.; Frick, L.W.; Nelson, D.J.;
Dornsife, R.E.; Wurster, J.A.; Wilson, L.J.; Fyfe, J.A.; Tuttle, J.V.; Miller,
W.H.; Condreay, L.; Avereet, D.R.; Schinazi, R.F.; Painter, G.R. The anti-
hepatitis B virus activities, cytotoxicities, and anabolic profiles of the (ꢀ) and
(þ) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxothiolan-5-yl]-
cytosine. Antimicrob. Agents Chemother 1992, 36, 2686–2692. Chem. Abstr.
1993, 118, 93802f.
5. Schinazi, R.F.; Gosselin, G.; Faraj, A.; Korba, B.E.; Liotta, D.C.; Chu, C.K.;
Mathe, C.; Imbach, J.; Sommadossi, J. Pure nucleoside enantiomers of b-20,30-
dideoxycytidine analogs are selective inhibitors of hepatitis B virus in vitro.
Antimicrob. Agents Chemother 1994, 38, 2172–2174. Chem. Abstr. 1994,
121, 200749e.
6. Coates, J.A.V.; Cammack, N.; Jenkinson, H.J.; Jowett, A.J.; Jowett, M.I.;
Pearson, B.A.; Penn, C.R.; Rouse, P.L.; Viner, K.C.; Cameron, J.M. (ꢀ)-20-
Deoxy-30-thiacytidine is a potent, highly selective inhibitor of human immuno-
deficiency virus type 1 and type 2 replication in vitro. Antimicrob. Agents
Chemother 1992, 36, 733–739. Chem. Abstr. 1992, 116, 211044u.
7. Doong, S.L.; Tsai, C.H.; Schinazi, R.F.; Liotta, D.C.; Cheng, Y.C. Inhibition
of the replication of hepatitis B virus in vitro by 20,30-dideoxy-30-thiacytidine
and related analog. Proc. Natl. Acad. Sci. USA 1991, 88, 8495–8499. Chem.
Abstr. 1991, 115, 269987z.
8. Chang, C.N.; Skalski, V.; Zhou, J.H.; Cheng, Y.C. Biochemical pharmacology
of the (þ)– and (ꢀ)-20,30-dideoxy-30-thiacytidine as antihepatitis B virus agents.
J. Biol. Chem. 1992, 267, 22,414–22,420. Chem. Abstr. 1992, 117, 225781q.
9. Grove, K.L.; Guo, X.; Liu, S.H.; Gao, Z.; Chu, C.K.; Cheng, Y.C. Anticancer
activity of b-l-dioxolanecytidine, a novel nucleoside analog with the unnatural
L configuration. Cancer Res. 1995, 55, 3008–3011. Chem. Abstr. 1995, 123,
132205p.
10. Pai, S.B.; Liu, S.H.; Zhu, Y.L.; Chu, C.K.; Cheng, Y.C. Inhibition of hepatitis
B virus by a novel l-nucleoside, 20-fluoro-5-methyl-b-l-arabinofuranosyl
uracil. Antimicrob. Agents Chemother 1996, 40, 380–386. Chem. Abstr.
1996, 124, 219475w.
11. Pelicano, H.; Pierra, C.; Eriksson, S.; Gosselin, G.; Imbach, J.L.; Maury, G.
Enzymatic properties of the unnatural b-l-enantiomers of 20,30-dideoxyadeno-
sine and 20,30-didehydro-20,30dideoxyadenosine. J. Med. Chem. 1997, 40, 3969–
3973. Chem Abstr. 1998, 128, 18411f.
12. Mansour, A.K.; Ibrahim, Y.A.; Eid, M.M. Nucleoside derivatives of 1,2,4-tri-
azine. Reaction of some derivatives of 1,2,4-triazine with tetra O-acetyle-a-d-
glucopyranosyl bromide. Z. Naturforsch 1976, 31b, 505–508.
13. Mansour, A.K.; Ibrahim, Y.A.; Eid, M.M.; Abdel-Hady, S. A.L.N-Glucosyl
derivatives of some 1,2,4-triazines with tetra-O-acetyl-a-d-glucopyranosyl bro-
mide. J. Carbohydrates. Nucleosides. Nucleotides 1981, 8 (2), 81–99.
14. Ibrahim, Y.A. Facile approach for the selective glycosidation of cyclic asym-
metric amides and thioamides. Carbohydrate Leters 1996, 1, 425–432.

Synthesis of Some New 2-a-l-Arabinopyranosyl-1,2,4-triazines
1823
15. Ibrahim, Y.A. Synthesis and structure of 2-deoxyribosyl-6-azauracil deriva-
tives. Carbohydrate Letters 1996, 2, 189–195.
16. Mansour, A.J.; Ibrahim, Y.A.; Khalil, N.S.A.M. Selective synthesis and struc-
ture of 6-arylvinyl-2-and 4-glucosyl-1,2,4-triazines of expected interesting bio-
logical activity. Nucleosides & Nucleotides 1999, 18 (10), 2265–2283.
17. Eid, M.M.; Abdelhady, S.A.; Ali, H.A.W. Reaction of some 1,2,4-triazines
with acetobromoglucose. Arch. Pharm. 1990, 323 (4), 243–245.
18. Dornow, A.; Menzel, H.; Marx, P. Synthesen sticktoffhaltiger heterocyclen,
¨
XXVII. Uber 1.2.4-triazine, I. Darstellung einiger neuer s-triazolo [3.2-c]-as-
triazine. Chem. Ber. 1964, 97, 2173–2178.
19. Ahmad, R.; Ajaz, S. Synthesis of 6-(p-Halobenzyl)-1,2,4-triazine-3,5(2H, 4H)-
dithiones having potential antimicrobial activity. J. Chem. Soc. Pak. 1985,
7 (4), 315–320.
20. Badawy, M.A.; Abdel-Hady, S.A.L.; Eid, M.M.; Ibrahim, Y.A. Synthesis and
structure of as-triazinoquinolines, II. Chem. Ber. 1984, 117, 1083–188.
21. Mansour, A.K.; Eid, M.M.; Hassan, R.A.; Haemers, A.; Pattyn, S.R.; Vanden
Berghe, D.A.; Van. Hoof, L. Synthesis, reactions and biological evaluation of
some 1,2,3-triazine derivatives. J. Heterocycl. Chem. 1988, 25, 279–283.
22. Furniss, B.S.; Hannaford, A.J.; Rogers, V.; Smith, P.W.G.; Tatchell, A.R.
Vogel’s Textbook of Practical Organic Chemistry; Longman group Limited,
1978; Vol. 4, 458pp.
Received January 28, 2003
Accepted April 10, 2003