Synthesis of some novel N-ribosyl-1,2,4-triazin-6(1H)-/ones or thiones as potential antibacterial and antifungal chemotherapeutics

Article abstract of DOI:10.1081/NCN-200051902

Ribosylation of 3-aryl-5-benzyl(or substituted benzyl)-1,2,4-triazin-6(1H)- /ones or thiones with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose gave the corresponding 3-aryl-5-benzyl(or substituted benzyl)-1-(2,3,5-tri-O-benzoyl- β-D-ribofuranosyl)-1,2,4-triazin-6(1H)-/ones or thiones. The structure of the new ribosides was confirmed chemically and spectroscopically. Copyright

Full text of DOI:10.1081/NCN-200051902

Nucleosides, Nucleotides, and Nucleic Acids, 24 (2):111–120, (2005)
Copyright D 2005 Taylor & Francis, Inc.
ISSN: 1525-7770 print/ 1532-2335 online
DOI: 10.1081/NCN-200051902
SYNTHESIS OF SOME NOVEL N-RIBOSYL-1,2,4-TRIAZIN-6(1H)-/ONES
OR THIONES AS POTENTIAL ANTIBACTERIAL AND
ANTIFUNGAL CHEMOTHERAPEUTICS
5
Nasser S. A. M. Khalil
Central Laboratory for Food and Feed, Agricultural Research
Center, Giza, Egypt
5
Ribosylation of 3-aryl-5-benzyl(or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones with 1-
O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranose gave the corresponding 3-aryl-5-benzyl(or substituted
benzyl)-1-(2,3,5-tri-O-benzoyl-b-D-ribofuranosyl)-1,2,4-triazin-6(1H)-/ones or thiones. The structure
of the new ribosides was confirmed chemically and spectroscopically.
Keywords Synthesis, b-D-Ribosyls, 1,2,4-Triazines, Antibacterial, Antifungal
INTRODUCTION
N-Glycosides of 1,2,4-triazines are considered to be one of the most biologically
active classes of compounds, possessing a wide spectrum of activities such as
cytotoxics, antivirals, enzyme inhibitors, immunosuppressives, antipsoriatics,
bacteriostatics, antitumors, as well as floor and wall disinfectants.[1–10] Therefore,
it would be of interest to synthesize some novel N-ribosides of 3-aryl-5-benzyl(or
substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones of expected interesting
biological activities and report the antimicrobial screening of three selected
compounds. The glucosyl and galactosyl analogues are reported.[11,12]
RESULTS AND DISCUSSION
In the present investigation, the starting 3-aryl-5-benzyl(or substituted benzyl)-
1,2,4-triazin-6(1H)-/ones 1a–d or thiones 5a–d were allowed to react with 1-O-
acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranose 2 to give the corresponing 3-aryl-5-benzyl
(or substituted benzyl)-1-(2,3,5-tri-O-benzoyl-b-D-ribofuranosyl)-1,2,4-triazin-6(1H)-/
ones 3a–d or thiones 6a–d following a simplified one-step/one-pot nucleoside
Received 2 September 2004, accepted 17 December 2004.
Address correspondence to Nasser S. A. M. Khalil, Central Laboratory for Food and Feed, Agricultural
Research Center, Giza, Egypt; E-mail: nasserkhalil_23@hotmail.com
111
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N. S. A. M. Khalil
SCHEME 1 Synthesis of N-ribosyl-1,2,4-triazin-6(1H)/ones or thiones.

N-Ribosyl-1,2,4-Triazin-6(1H)/Ones or Thiones
113
synthesis as shown in Scheme 1. The structures of compounds 3a–d, 6a–d were
assigned based on the following evidences:
1
1. The b-configuration of compounds 3a–d, 6a–d is confirmed from their H
NMR spectral data, which revealed the anomeric proton at d 6.82–6.62 with a
coupling constant consistent with similar reported data.[13–16]
2. The IR spectra of compounds 3a–d showed the amide carbonyl function at
1674–1666 cmꢀ 1
.
3. Thiation of compounds 3a–d gave the corresponding thiones 6a–d, which
their IR spectra showed the absence of the amide carbonyl function at 1674–
1666 cmꢀ 1
.
Debenzoylation of compounds 3a–d, 6a–d was achieved via their treatment
with methanolic ammonia to give the free ribosides 4a–d, 7a–d, respectively.
The structure of compounds 4a–d, 7a–d was confirmed based on their analytical
and spectral data. Thus, the IR spectra of these compounds not only showed the
absence of the ester carbonyl function at 1728 cmꢀ1, but also showed the
1
appearance of the hydroxyl function at 3669–3400 cmꢀ1. Moreover, the H NMR
data of these compounds revealed the absence of the aromatic protons of the
benzoate groups at d 8.30–7.02 (via calculation of proton integration ratios) and the
appearance of the exchangeable OH protons’ signals at d 5.18–4.59.
Biological Evaluation
As a part of our program directed toward the synthesis of new 1,2,4-triazine
nucleosides with possible potential biological activity,[9,10,12,17,18] compounds 7b d
were tested for antimicrobial activity (in vitro) against against Aspergillus fumigatus,
Penicillium italicum, Syncephalastrum racemosum, Candida albicans, Staphylococcus
aureus, Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli. Table 1 shows the
inhibitory effects of compounds 7b d against these organisms. The screening
results of these compounds showed that compound 7d having a Cl atom has
the greatest inhibitory effect against one or more types of microorganisms fol-
lowed by compound 7c having a methoxy group then compound 7b having a
methyl group. Thus, compound 7b showed moderate activity against Aspergillus
fumigatus (at all tested concentrations; 5, 2.5, 1 mg/mL), Penicillium italicum (at
concentration 5 mg/mL), Syncephalastrum racemosum (at concentration 5 mg/mL),
and Escherichia coli (at concentration 5 mg/mL). Compound 7c showed activity
against Aspergillus fumigatus (promising activity at concentration 5 mg/mL; mod-
erate activity at concentration 2.5 mg/mL), Penicillium italicum (moderate activity
at concentration 5 mg/mL), Candida albicans (moderate activity at all tested
concentrations; 5, 2.5, 1 mg/mL), and Escherichia coli (promising activity at con-
centration 5 mg/mL; moderate activity at concentration 2.5 mg/mL). Compound 7d
showed activity against Aspergillus fumigatus (promising activity at concentrations
5, 2.5 mg/mL; moderate activity at concentration 1 mg/mL), Penicillium italicum

114
N. S. A. M. Khalil
TABLE 1 Antimicrobial Activity of Compounds 7b = d Compared to Standard Antimicrobial Agents
Compounds
7ba
7ca
7da
St.b
2.5
Test organisms
5
2.5
1
5
2.5
1
5
2.5
1
5
1
Aspergillus fumigatus
Penicillium italicum
Syncephalastrum racemosum
Candida albicans
Staphylococcus aureus
Pseudomonas aeruginosa
Bacillus subtilis
+
+
+
0
0
0
0
+
+
0
0
0
0
0
0
0
+
0
0
0
0
0
0
0
++
+
0
+
0
+
+
++
+
0
0
+
0
+
0
+
0
0
0
+
0
+
0
0
++
++
0
+
0
0
0
+++
++
++
0
+
0
0
0
++
+
+
0
+
0
0
+++
+++
+++
++
++
+++
++
+++
+++
+++
++
++
++
++
++
+++
++
++
++
++
++
0
++
++
++
Escherichia coli
+++
Note: The test was done using the diffusion agar technique. Inhibition values = 0.1–0.5 cm beyond
control = +; Inhibition values = 0.6–1.0 cm beyond control = ++; Inhibition values = 1.1–1.5 cm beyond
control = +++; 0 = not detected.
a100 ml of each conc. (5, 2.5, 1 mg/mL) was tested.
bSt. = Reference standard; Chloramphenicol was used as a standard antibacterial agent and Terbinafin was used
as a standard antifungal agent.
(promising activity at concentrations 5, 2.5 mg/mL; moderate activity at concen-
tration 1 mg/mL), Candida albicans (moderate activity at all tested concentrations;
5, 2.5, 1 mg/mL), and Escherichia coli (as potent as standard chloramphenicol at all
tested concentrations).
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded on a Perkin-
1
Elmer 1430 spectrometer. H NMR spectra were recorded at 200 MHz with a
Varian GEMINI 200 spectrometer. The abbreviations pt and pq denote
pseudotriplet and pseudoquartet signals, respectively. The starting compounds
1a–d,[19,20] 5a–d[11] were prepared as reported. TLC was performed on Fluka
silica gel 60 F254 aluminum sheets, and products were detected using 254 nm light.
Fluka silica gel 60 (70–230 mesh) was used for column chromatography. Elemental
analyses were carried out at the Micro Analytical Center, Cairo University, Giza,
Egypt. Antimicrobial screening of compounds 7b d was carried out at the Medical
Mycology Lab, the Regional Center for Mycology and Biotechnology, Al Azhar
University, Cairo, Egypt.
5-Benzyl (or substituted benzyl)-3-phenyl-1-(2,3,5-tri-O-ben-
zoyl-b-D-ribofuranosyl)-1,2,4-triazin-6(1H)-ones (3a-d).
General Procedure. To a mixture of each of compounds 1a–d (2
mmol) and 1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranose (2) (2 mmol) in acetoni-
trile (20 mL) were added consecutively hexamethyldisilazane (2.2 mmol),

N-Ribosyl-1,2,4-Triazin-6(1H)/Ones or Thiones
115
trimethylchlorosilane (2.2 mmol), and trifluoromethanesulfonic acid (2.4 mmol).
The reaction mixture was heated at reflux temperature with exclusion of humidity
(using CaCl2 guard tube fitted over the refluxing condenser) until the reaction was
judged complete by TLC (18–24 h), using petroleum ether (bp 40–60°C)/EtOAc
(60:40, v/v) as a developing system. The excess acetonitrile was evaporated on a
rotavap and the formed residue was dissolved in dichloromethane (30 mL), washed
(NaHCO3, brine), dried (Na2SO4), evaporated, column chromatographed
(petroleum ether [bp 40–60°C] ! 60% EtOAc/petroleum ether [bp 40–60°C]),
and recrystallized from dichloromethane/petroleum ether (bp 40–60°C) to give
pale yellow crystals of compounds 3a–d.
5-Benzyl-3-phenyl-1-(2,3,5-tri-O-benzoyl-b-D-ribofuranosyl)-
1,2,4-triazin-6(1H)-one (3a). Using the general procedure, 1a gave 3a
(75%); Rf = 0.87; mp 114°C; IR (KBr) 1728 (C = O benzoate), 1674 (C = O amide)
1
cmꢀ 1; H NMR (DMSO-d6) d 8.14–7.17 (m, 25H, ArH), 6.74 (d, 1H, J = 4.8 Hz,
H-1’), 6.32 (pt, 1H, J = 5.5 Hz, H-2’), 6.24 (pt, 1H, J = 5.3 Hz, H-3’), 4.76 (m, 1H, H-
4’), 4.68 (dd, 1H, J = 4.0 Hz, 11.5 Hz, H-5’), 4.48 (dd, 1H, J = 4.5 Hz, 11.7 Hz, H-
5@), 4.23 (s, 2H, C6H5CH2). Anal. Calcd. for C42H33N3O8: C, 71.28; H, 4.70; N,
5.94. Found: C, 71.44; H, 4.63; N, 5.68.
5-(4-Methylbenzyl)-3-phenyl-1-(2,3,5-tri-O-benzoyl-b-D-ribofu-
ranosyl)-1,2,4-triazin-6(1H)-one (3b). Using the general procedure, 1b
gave 3b (72%); Rf = 0.85; mp 130°C; IR (KBr) 1728 (C = O benzoate), 1666
1
(C = O amide) cmꢀ 1; H NMR (DMSO-d6) d 8.3–7.02 (m, 24H, ArH), 6.62 (d,
1H, J = 5.0 Hz, H-1’), 6.29 (pt, 1H, J = 5.2 Hz, H-2’), 6.16 (pt, 1H, J = 5.3 Hz, H-
3’), 4.82 (m, 1H, H-4’), 4.66 (dd, 1H, J = 4.1 Hz, 11.3 Hz, H-5’), 4.44 (dd, 1H,
J = 4.3 Hz, 11.5 Hz, H-5@), 4.12 (s, 2H, 4-CH3C6H4CH2), 2.28 (s, 3H, 4-
CH3C6H4CH2). Anal. Calcd. for C43H35N3O8: C, 71.56; H, 4.89; N, 5.82. Found:
C, 71.71; H, 4.83; N, 5.77.
5-(4-Methoxybenzyl)-3-phenyl-1-(2,3,5-tri-O-benzoyl-b-D-ribo-
furanosyl)-1,2,4-triazin-6(1H)-one (3c). Using the general procedure,
1c gave 3c (83%); Rf = 0.84; mp 116°C; IR (KBr) 1728 (C = O benzoate), 1674
(C = O amide) cmꢀ 1; 1H NMR (DMSO-d6) d 8.11–7.36 (m, 24H, ArH), 6.75 (d, 1H,
J = 4.9 Hz, H-1’), 6.35 (pt, 1H, J = 5.6 Hz, H-2’), 6.19 (pt, 1H, J = 5.4 Hz, H-3’), 4.89
(m, 1H, H-4’), 4.61 (dd, 1H, J = 4.2 Hz, 11.4 Hz, H-5’), 4.52 (dd, 1H, J = 4.4 Hz,
11.9 Hz, H-5@), 3.90 (s, 2H, 4-CH3OC6H4CH2), 3.76 (s, 3H, 4-CH3OC6H4CH2). Anal.
Calcd. for C43H35N3O9: C, 70.01; H, 4.78; N, 5.70. Found: C, 70.20; H, 4.69; N, 5.74.
5-(4-Chlorobenzyl)-3-phenyl-1-(2,3,5-tri-O-benzoyl-b-D-ribofu-
ranosyl)-1,2,4-triazin-6(1H)-one (3d). Using the general procedure, 1d
gave 3d (85%); Rf = 0.79; mp 117°C; IR (KBr) 1728 (C = O benzoate), 1674 (C = O
1
amide) cmꢀ 1; H NMR (DMSO-d6) d 8.14–7.14 (m, 24H, ArH), 6.74 (d, 1H,

116
N. S. A. M. Khalil
J = 4.8 Hz, H-1’), 6.34 (pt, 1H, J = 5.3 Hz, H-2’), 6.16 (pt, 1H, J = 5.5 Hz, H-3’), 4.85
(m, 1H, H-4’), 4.64 (dd, 1H, J = 4.2 Hz, 11.4 Hz, H-5’), 4.56 (dd, 1H, J = 4.4 Hz,
11.7 Hz, H-5@), 4.23 (s, 2H, 4-ClC6H4CH2). Anal. Calcd. for C42H32ClN3O8: C,
67.97; H, 4.35; N, 5.66. Found: C, 68.02; H, 4.44; N, 5.75.
5-Benzyl (or substituted benzyl)-3-phenyl-1-(2,3,5-tri-O-ben-
zoyl-b-D-ribofuranosyl)1,2,4-triazin-6(1H)-thiones (6a–d).
General Procedure (A). To a mixture of each of compounds 5a–d (2
mmol) and 1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranose (2) (2 mmol) in acetoni-
trile (20 mL) were added consecutively hexamethyldisilazane (2.2 mmol),
trimethylchlorosilane (2.4 mmol), and trifluoromethanesulfonic acid (2.4 mmol).
The reaction mixture was heated at reflux temperature with exclusion of humidity
(using CaCl2 guard tube fitted over the refluxing condenser) until the reaction was
judged complete by TLC (18–24 h), using petroleum ether (bp 40–60°C)/EtOAc
(60:40, v/v) as a developing system. The excess acetonitrile was evaporated on a
rotavap and the formed residue was dissolved in dichloromethane (30 mL), washed
(NaHCO3, brine), dried (Na2SO4), evaporated, column chromatographed
(petroleum ether [bp 40–60°C] ! 60% EtOAc/petroleum ether [bp 40–60°C])
and recrystallized from dichloromethane/petroleum ether (bp 40–60°C) to give
yellow crystals of compounds 6a–d.
General Procedure (B). To a solution of each of compounds 3a–d
(1 mmol) in dry pyridine (5 mL) was added phosphorous pentasulfide (2 mmol).
The reaction mixture was heated at reflux temperature for 6 h. After cooling, the
products were extracted from the oily materials with ethanol (10 mL). The
supernatant solutions were decanted, acidified with acetic acid (0.5 mL),
concentrated, and diluted with water. The precipitates were collected by filtration,
dried at room temperature, dissolved in diethyl ether, and treated with charcoal
(0.5 g), filtered, and the filtrates evaporated at room temperature. The resulting
solids were recrystallized from diethyl ether/petroleum ether (bp 40–60°C) to give
yellow crystals of compounds 6a–d.
5-Benzyl-3-phenyl-1-(2,3,5-tri-O-benzoyl-b-D-ribofuranosyl)-
1,2,4-triazin-6(1H)-thione (6a). Using the general procedure (A) or (B)
with 5a or 3a, respectively, gave 6a (77% or 55%); Rf = 0.89; mp 122°C; IR (KBr)
1
1728 (C = O benzoate) cmꢀ 1; H NMR (DMSO-d6) d 8.12–7.13 (m, 25H, ArH),
6.77 (d, 1H, J = 4.9 Hz, H-1’), 6.37 (pt, 1H, J = 5.1 Hz, H-2’), 6.19 (pt, 1H, J = 5.4
Hz, H-3’), 4.82 (m, 1H, H-4’), 4.69 (dd, 1H, J = 4.2 Hz, 11.4 Hz, H-5’), 4.48 (dd,
1H, J = 4.4 Hz, 11.5 Hz, H-5@), 4.22 (s, 2H, C6H5CH2). Anal. Calcd. for
C42H33N3O7S: C, 69.70; H, 4.60; N, 5.81; S, 4.43. Found: C, 69.84; H, 4.72; N,
5.92; S; 4.52.

N-Ribosyl-1,2,4-Triazin-6(1H)/Ones or Thiones
117
5-(4-Methylbenzyl)-3-phenyl-1-(2,3,5-tri-O-benzoyl-b-D-ribofu-
ranosyl)-1,2,4-triazin-6(1H)-thione (6b). Using the general procedure
(A) or (B) with 5b or 3b, respectively, gave 6b (75% or 54%); Rf = 0.83; mp 146°C;
IR (KBr) 1728 (C = O benzoate) cmꢀ 1; 1H NMR (DMSO-d6) d 8.29–7.13 (m, 24H,
ArH), 6.74 (d, 1H, J = 5.3 Hz, H-1’), 6.25 (pt, 1H, J = 5.2 Hz, H-2’), 6.19 (pt, 1H,
J = 5.4 Hz, H-3’), 4.88 (m, 1H, H-4’), 4.66 (dd, 1H, J = 4.1 Hz, 11.0 Hz, H-5’), 4.44
(dd, 1H, J = 4.3 Hz, 11.2 Hz, H-5@), 4.19 (s, 2H, 4-CH3C6H4CH2), 2.25 (s, 3H, 4-
CH3C6H4CH2). Anal. Calcd. for C43H35N3O7S: C, 70.00; H, 4.78; N, 5.70; S, 4.35.
Found: C, 69.92; H, 4.89; N, 5.61; S, 4.44.
5-(4-Methoxybenzyl)-3-phenyl-1-(2,3,5-tri-O-benzoyl-b-D-ribo-
furanosyl)-1,2,4-triazin-6(1H)-thione (6c). Using the general proce-
dure (A) or (B) with 5c or 3c, respectively, gave 6c (85% or 57%); Rf = 0.79; mp
122°C; IR (KBr) 1728 (C = O benzoate) cmꢀ 1; 1H NMR (DMSO-d6) d 8.14–7.30
(m, 24H, ArH), 6.82 (d, 1H, J = 5.0 Hz, H-1’), 6.32 (pt, 1H, J = 5.1 Hz, H-2’), 6.22
(pt, 1H, J = 5.5 Hz, H-3’), 4.84 (m, 1H, H-4’), 4.63 (dd, 1H, J = 4.1 Hz, 11.2 Hz,
H-5’), 4.55 (dd, 1H, J = 4.3 Hz, 11.6 Hz, H-5@), 3.96 (s, 2H, 4-CH3OC6H4CH2), 3.78
(s, 3H, 4-CH3OC6H4CH2). Anal. Calcd. for C43H35N3O8S: C, 68.51; H, 4.68; N,
5.57; S, 4.25. Found: C, 68.54; H, 4.79; N, 5.48; S, 4.18.
5-(4-Chlorobenzyl)-3-phenyl-1-(2,3,5-tri-O-benzoyl-b-D-ribofu-
ranosyl)-1,2,4-triazin-6(1H)-thione (6d). Using the general procedure
(A) or (B) with 5d or 3d, respectively, gave 6d (86% or 60%); Rf = 0.79; mp 128–
130°C; IR (KBr) 1728 (C = O benzoate) cmꢀ 1; 1H NMR (DMSO-d6) d 8.12–7.15
(m, 24H, ArH), 6.72 (d, 1H, J = 4.9 HzH-1’), 6.31 (pt, 1H J = 5.6 Hz, H-2’), 6.14 (pt,
1H, J = 5.7 Hz, H-3’), 4.80 (m, 1H, H-4’), 4.62 (dd, 1H, J = 4.2 Hz, 11.1 Hz, H-5’),
4.56 (dd, 1H, J = 4.3 Hz, 11.6 Hz, H-5@), 4.25 (s, 2H, 4-ClC6H4CH2). Anal. Calcd.
for C42H32ClN3O7S: C, 66.53; H, 4.25; N, 5.54; S, 4.23. Found: C, 66.48; H, 4.39; N,
5.66; S, 4.34.
5-Benzyl-3-phenyl-1-b-D-ribofuranosyl-1,2,4-triazin-6(1H)-ones
(4a–d)/or thiones (7a–d).
General Procedure. Dry gaseous ammonia was passed through a
solution of each of compounds 3a–d or 6a–d (1 mmol) in dry methanol (10 mL)
for about 1 h while cooling and stirring. The reaction mixture was kept stirring at
room temperature until complete as shown by TLC (10 to 24 h), using chloroform/
methanol (80:20, v/v) as a developing system. The resulting mixture was then
concentrated at reduced pressure to afford a semisolid residue, which was boiled
in chloroform (100 mL), collected by discarding chloroform via decantation,
washed several times with boiled chloroform, collected again by discarding
chloroform via decantation, dried at room temperature, column chromatographed

118
N. S. A. M. Khalil
(chloroform ! 20% methanol/chloroform), and recrystallized from methanol
to give pale crystals of compounds 4a–d and pale yellow crystals of compounds
7a–d.
5-Benzyl-3-phenyl-1-b-D-ribofuranosyl-1,2,4-triazin-6(1H)-one
(4a). Using the general procedure, 3a gave 4a (80%);Rf = 0.92; mp 175°C; IR
(KBr) 3663–3429 (OH), 1673 (C = O amide) cmꢀ 1; 1H NMR (DMSO-d6) d 8.09–
7.11 (m, 10H, ArH), 6.56 (d, 1H, J = 4.0 Hz, H-1’), 5.11 (d, 1H, J = 5.6 Hz, 2’-OH-
exchangeable), 4.92 (d, 1H, J = 6.5 Hz, 3’-OH-exchangeable), 4.62 (t, 1H, J = 5.3
Hz, 5’-OH-exchangeable), 4.56 (pt, 1H, J = 5.2 Hz, H-2’), 4.19 (pq, 1H, H-3’), 3.78
(m, 1H, H-4’), 3.66 (dd, 1H, J = 4.5 Hz, 11.6 Hz, H-5’), 3.53 (dd, 1H, J = 4.7 Hz,
11.6 Hz, H-5@), 4.21 (s, 2H, C6H5CH2). Anal. Calcd. for C21H21N3O5: C, 63.79; H,
5.35; N, 10.63. Found: C, 63.66; H, 5.24; N, 10.74.
5-(4-Methylbenzyl)-3-phenyl-1-b-D-ribofuranosyl-1,2,4-triazin-
6(1H)-one (4b). Using the general procedure, 3b gave 4b (78%);Rf = 0.88;
1
mp 197°C; IR (KBr) 3661–3422 (OH), 1673 (C = O amide) cmꢀ 1; H NMR
(DMSO-d6) d 8.12–7.14 (m, 9H, ArH), 6.59 (d, 1H, J = 4.1 Hz, H-1’), 5.14 (d, 1H,
J = 5.2 Hz, 2’-OH-exchangeable), 4.99 (d, 1H, J = 6.2 Hz, 3’-OH-exchangeable),
4.61 (t, 1H, J = 5.2 Hz, 5’-OH-exchangeable), 4.55 (pt, 1H, J = 5.4 Hz, H-2’), 4.29
(pq, 1H, H-3’), 3.79 (m, 1H, H-4’), 4.18 (s, 2H, 4-CH3C6H4CH2), 3.61 (dd, 1H,
J = 4.4 Hz, 11.4 Hz, H-5’), 3.52 (dd, 1H, J = 4.4 Hz, 11.7 Hz, H-5@), 2.25 (s, 3H, 4-
CH3C6H4CH2). Anal. Calcd. for C22H23N3O5: C, 64.54; H, 5.66; N, 10.26. Found:
C, 64.44; H, 5.49; N, 10.37.
5-(4-Methoxybenzyl)-3-phenyl-1-b-D-ribofuranosyl-1,2,4-tria-
zin-6(1H)-one (4c). Using the general procedure, 3c gave 4c (78%);
Rf = 0.87; mp. 201–202°C; IR (KBr) 3661–3400 (OH), 1673 (C = O amide)
cmꢀ 1; 1H NMR (DMSO-d6) d 8.07–7.16 (m, 9H, ArH), 6.61 (d, 1H, J = 4.7 Hz, H-
1’), 5.17 (d, 1H, J = 5.5 Hz, 2’-OH-exchangeable), 4.91 (d, 1H, J = 6.7 Hz, 3’-OH-
exchangeable), 4.59 (t,1H, J = 5.0 Hz, 5’-OH-exchangeable), 4.62 (pt, 1H, J = 5.4
Hz, H-2’), 4.26 (pq, 1H, H-3’), 3.92 (s, 3H, 4-CH3OC6H4CH2), 3.78 (s, 2H, 4-
CH3OC6H4CH2), 3.71 (m, 1H, H-4’), 3.66 (dd, 1H, J = 4.4 Hz, 11.3 Hz, H-5’), 3.53
(dd, 1H, J = 4.2 Hz, 11.3 Hz, H-5@). Anal. Calcd. for C22H23N3O6: C, 62.11; H,
5.45; N, 9.88. Found: C, 62.01; H, 5.64; N, 10.02.
5-(4-Chlorobenzyl)-3-phenyl-1-b-D-ribofuranosyl-1,2,4-triazin-
6(1H)-thione (4d). Using the general procedure, 3d gave 4d (78%);
Rf = 0.90; mp 194–196°C; 3670–3421 (OH), 1673 (C = O amide) cmꢀ 1; 1H
NMR (DMSO-d6) d 8.11–7.06 (m, 9H, ArH), 6.57 (d, 1H, J = 4.5 Hz, H-1’), 5.18
(d, 1H, J = 5.6 Hz, 2’-OH-exchangeable), 4.97 (d, 1H, J = 6.4 Hz, 3’-OH-
exchangeable), 4.62 (t, 1H, J = 5.1 Hz, 5’-OH-exchangeable), 4.55 (pt, 1H, J = 5.2
Hz, H-2’), 4.24 (pq, 1H, H-3’), 3.76 (m, 1H, H-4’), 3.62 (dd, 1H, J = 4.6 Hz, 11.3

N-Ribosyl-1,2,4-Triazin-6(1H)/Ones or Thiones
119
Hz, H-5’), 3.53 (dd, 1H, J = 4.7 Hz, 11.4 Hz, H-5@), 4.17 (s, 2H, 4-ClC6H4CH2).
Anal. Calcd. for C21H20ClN3O5: C, 58.68; H, 4.69; N, 9.78. Found: C, 58.84; H,
4.51; N, 9.66.
5-Benzyl-3-phenyl-1-b-D-ribofuranosyl-1,2,4-triazin-6(1H)-thi-
one (7a). Using the general procedure, 6a gave 7a (79%); Rf = 0.96; mp
1
152–154°C; IR (KBr) 3660–3425 (OH) cmꢀ 1; H NMR (DMSO-d6) d 8.14–
7.17 (m, 10H, ArH), 6.54 (d, 1H, J = 4.3 Hz, H-1’), 5.14 (d, 1H, J = 5.9 Hz, 2’-
OH-exchangeable), 4.96 (d, 1H, J = 6.7 Hz, 3’-OH-exchangeable), 4.66 (t, 1H,
J = 5.0 Hz, 5’-OH-exchangeable), 4.58 (pt, 1H, J = 5.5 Hz, H-2’), 4.25 (pq, 1H,
H-3’), 3.76 (m, 1H, H-4’), 3.68 (dd, 1H, J = 4.7 Hz, 11.7 Hz, H-5’), 3.51 (dd,
1H, J = 4.8 Hz, 11.9 Hz, H-5@), 4.23 (s, 2H, C6H5CH2). Anal. Calcd. for
C21H21N3O4S: C, 61.30; H, 5.14; N, 10.21; S, 7.79. Found: C, 61.24; H, 5.02;
N, 10.34; S, 7.95.
5-(4-Methylbenzyl)-3-phenyl-1-b-D-ribofuranosyl-1,2,4-triazin-
6(1H)-thione (7b). Using the general procedure, 6b gave 7b (75%);
Rf = 0.95; mp 169°C IR (KBr) 3667–3425 (OH) cmꢀ 1; 1H NMR (DMSO-d6) d
8.19–7.11 (m, 9H, ArH), 6.64 (d, 1H, J = 4.5 Hz, H-1’), 5.16 (d, 1H, J = 5.7 Hz, 2’-
OH-exchangeable), 4.98 (d, 1H, J = 6.5 Hz, 3’-OH-exchangeable), 4.63 (t, 1H, J = 5
Hz, 5’-OH-exchangeable), 4.58 (pt, 1H, J = 5.3 Hz, H-2’), 4.27 (pq, 1H, H-3’), 3.78
(m, 1H, H-4’), 4.23 (s, 2H, 4-CH3C6H4CH2), 3.67 (dd, 1H, J = 4.5 Hz, 11.6 Hz, H-
5’), 3.52 (dd, 1H, J = 4.7 Hz, 11.8 Hz, H-5@), 2.27 (s, 3H, 4-CH3C6H4CH2). Anal.
Calcd. for C22H23N3O4S: C, 62.10; H, 5.45; N, 9.88; S, 7.54. Found: C, 62.23; H,
5.56; N, 9.62; S, 7.68.
5-(4-Methoxybenzyl)-3-phenyl-1-b-D-ribofuranosyl-1,2,4-tria-
zin-6(1H)-thione (7c). Using the general procedure, 6c gave 7c (87%);
1
Rf = 0.89; mp 201–203°C; IR (KBr) 3669–3438 cmꢀ 1; H NMR (DMSO-d6) d
8.11–7.23 (m, 9H, ArH), 6.54 (d, 1H, J = 4.5 Hz, H-1’), 5.12 (d, 1H, J = 5.6 Hz, 2’-
OH-exchangeable), 4.94 (d, 1H, J = 6.6 Hz, 3’-OH-exchangeable), 4.62 (t, 1H,
J = 5.3 Hz, 5’-OH-exchangeable), 4.60 (pt, 1H, J = 5.4 Hz, H-2’), 4.26 (pq, 1H,
H-3’), 3.97 (s, 2H, 4-CH3OC6H4CH2), 3.77 (s, 3H, 4-CH3OC6H4CH2), 3.74 (m,
1H, H-4’), 3.65 (dd, 1H, J = 4.5 Hz, 11.7 Hz, H-5’), 3.51 (dd, 1H, J = 4.8 Hz, 11.6 Hz,
H-5@). Anal. Calcd. for C22H23N3O5S: C, 59.85; H, 5.25; N, 9.52; S, 7.26. Found: C,
60.03; H, 5.22; N, 9.74; S, 7.19.
5-(4-Chlorobenzyl)-3-phenyl-1-b-D-ribofuranosyl-1,2,4-triazin-
6(1H)-thione (7d). Using the general procedure, 6d gave 7d (81%);
1
Rf = 0.93; mp 222°C; 3660–3425 (OH) cmꢀ 1; H NMR (DMSO-d6) d 8.17–7.12
(m, 9H, ArH), 6.62 (d, 1H, J = 4.3 Hz, H-1’), 5.16 (d, 1H, J = 5.8 Hz, 2’-OH-
exchangeable), 4.96 (d, 1H, J = 6.8 Hz, 3’-OH-exchangeable), 4.67 (t, 1H,
J = 5.0Hz, 5’-OH-exchangeable), 4.58 (pt, 1H, J = 5.3 Hz, H-2’), 4.24 (pq, 1H, H-

120
N. S. A. M. Khalil
3’), 3.76 (m, 1H, H-4’), 3.67 (dd, 1H, J = 4.7 Hz, 11.6 Hz, H-5’), 3.53 (dd, 1H, J = 4.7
Hz, 11.9 Hz, H-5@), 4.21 (s, 2H, 4-ClC6H4CH2). Anal. Calcd. for C21H20ClN3O4S:
C, 56.56; H, 4.52; N, 9.42; S, 7.19. Found: C, 56.61; H, 4.42; N, 9.63, S, 7.34.
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