An improved direct synthetic approach to anhydronucleosides

Article abstract of DOI:10.1016/j.tet.2008.06.016

The synthesis of anhydrothioglycosyls has been improved by studying the reaction under a variety of reaction conditions including gas phase pyrolysis, heating in a solvent of high boiling point, in the presence of different bases including triethylamine, DABCO, and DBU, and in a microwave reactor.

Full text of DOI:10.1016/j.tet.2008.06.016

Tetrahedron 64 (2008) 8206–8212
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An improved direct synthetic approach to anhydronucleosides
*
Ibtehal A. Al-Juwaiser, Maher R. Ibrahim, Nouria A. Al-Awadi , Yehia A. Ibrahim
Chemistry Department, Faculty of Science, Kuwait University, PO Box 5969, Safat 13060, Kuwait
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of anhydrothioglycosyls has been improved by studying the reaction under a variety of
reaction conditions including gas phase pyrolysis, heating in a solvent of high boiling point, in the
presence of different bases including triethylamine, DABCO, and DBU, and in a microwave reactor.
Ó 2008 Published by Elsevier Ltd.
Received 27 March 2008
Received in revised form 19 May 2008
Accepted 5 June 2008
Available online 10 June 2008
Keywords:
Pyrolysis
Microwave
Nucleosides
Anhydronucleosides
1,2,4-Triazines
1. Introduction
talosyl, and 3,20-anhydro- -arabinosyl derivatives 3 (Scheme 1).9
b-D
The proposed mechanism for the thermal conversion of these
acylated glycosyls into their anhydro derivatives is illustrated in
Scheme 1. This involves the intramolecular SN2 (5-exo-tet) attack by
the sulfur on C-20 of the glycosyl moiety followed by elimination of
acetate (CH3COOꢀ) and Hþ, which ultimately produce acetic acid.9
The synthesis of 2,20- and 2,30-anhydronucleoside has attracted
considerable interest due to the possibility that these compounds
can be attacked by nucleophiles at the C-20 or C-30 positions
affording compounds with anti-AIDS activity.1 The first reported
method for the synthesis of 2,20-anhydronucleosides involved
treating 1-30,50-O-isopropylidene-20-O-methanesulfonyl-
b-D-xylo-
2. Results and discussions
furanosylthymine with sodium hydroxide in ethanol at reflux to
afford the corresponding 2,20-anhydronucleoside.2 Moreover, the
action of bases (NaHCO3/DMF, PhCOONa, or DB) on the appropriate
20-O-phenyloxycarbonyl or 20-O-methanesulfonyl derivatives of
nucleosides have been used to promote anhydrization.1d,f,g,3–5
Additionally, heating 20-deoxy-20-iodonucleosides in DMF with
di-n-butyltin oxide gave the corresponding anhydronucleosides.6
2,20-Anhydrothionucleosides have also been investigated and some
synthetic methods have been reported.7a,b Moreover, a method has
been reported for the synthesis of arabino-6-aza-2-thio-2,20-
anhydrouridine.8
In the present work, we have been able to convert 4a into the
anhydro derivative 7a thermally by static pyrolysis at 255 ꢁC. We
thought that based on the proposed mechanism the reaction could
be accomplished under milder conditions in the presence of
a suitable base. Hence we studied first the conversion of 4a into the
corresponding anhydro derivative 7a by heating in xylene in the
presence of DABCO, but no detectable product was found even after
24 h at reflux. However, upon heating in MW at 180–190 ꢁC for
10 min, the starting material completely disappeared and 62–67%
yield of the anhydro derivative 7a was isolated from this reaction
mixture. Changing the solvent to THF did not affect the yield of this
reaction noticeably. These conditions have been optimized for this
example by running the reaction at different temperature and
following the product/starting material ratio by different analytical
techniques including LCMS and NMR spectroscopy.
During our study for the thermal selective synthesis of 2-gly-
cosyl derivatives 2 from their corresponding 4-arylideneamino
derivatives 1, we accidentally discovered the gas phase thermal
intramolecular substitution reaction, which led to the conversion of
the 2-
rivatives of 3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-ones into
their corresponding 3,20-anhydro- -mannosyl, 3,20-anhydro-
b-D-
b-D-N-glucosyl, 2-b-D-N-galactosyl, and 2-b-D-N-ribosyl de-
The recently established fact that the MW effect is purely ther-
mal and not related to microwave field10 led us to investigate this
reaction in diphenyl ether (DPE) as a solvent of high boiling point.
Thus, when 4a and DABCO in DPE were heated at 190–200 ꢁC,
complete conversion took place, but the isolated yield of 7a was
b-
D
* Corresponding author. Fax: þ965 4816482.
E-mail address: nouria@kuc01.kuniv.edu.kw (N.A. Al-Awadi).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.06.016

I.A. Al-Juwaiser et al. / Tetrahedron 64 (2008) 8206–8212
8207
Ar
H
N
O
N
O
N
O
N
O
N
H
S
R
R
N
S
R
H
S
R
N
O
N
O
N
O
N
N
N
N
S
5-exo-tet
Δ
O
CH3COOH
+
-ArCN
AcO
H
AcO
AcO
AcO
OAc
OAc
OAc
1
2
3
Scheme 1.
only 40% most probably due to loss of products during isolation
from this solvent. An identical result was obtained by running the
reaction in nitrobenzene instead of DPE with little improvement in
the yield (49%, Table 1).
Also, conducting this reaction in ethylpyridinium tetra-
fluoroborate (ionic liquid, IL) in the presence of DABCO at 140 ꢁC
afforded 34% of the anhydro derivative 7a. Compared to the re-
action in xylene at the same temperature, it is clear that that IL
improves the conditions required for the desired conversion of 4a
into 7a. Table 1 summarizes the different conditions studied to
convert 4a into 7a.
In this work, we also studied the synthesis of further examples
of 2-glucosyl-1,2,4-triazines 4–6. The latter were successfully
converted into their corresponding anhydrothioglucosyls 7–9
(Scheme 2) using the conditions of entry 3 or 5 in Table 1. The
yields of the anhydro derivatives 7–9 were in the ranges shown in
Scheme 2.
O
N
O
R
R
HN
NN
H2
O
N
N
R
S
S
N
AcO
NN
H2
TEA/ABG
DMF
HNO2/CH3COOH
AcO
O
O
N
S
N
H
OAc
OAc
AcO
AcO
AcO
AcO
R
R
R
10a-c, e CH2Ar
11a, b, d Ar
13a-c, e CH2Ar
14a, b, d Ar
4a-c, e CH2Ar
5a, b, d Ar
12a-c, e, f CH=CHAr
15a-c, e, f CH=CHAr
6a-c, e, f CH=CHAr
Ar = a, C6H5, b, p-ClC6H4, c, p-CH3C6H4, d, p-CH3OC6H4, e, 2-thienyl, f, p-O2NC6H4
Scheme 3.
3. Conclusion
The present study explored the optimization of the reaction
conditions leading to efficient conversions of glycosyl derivatives
into their valuable anhydroglycosyl derivatives. The results
obtained thus far are promising, and encourage us to continue
further applications to convert other glycosyl derivatives into their
anhydroglycosyl derivatives, which will be a valuable starting ma-
terial for the synthesis of new potential biologically active glycosyl
derivatives.
Table 1
Yield and reaction conditions studied to convert 4a into 7a
Entry
Yield of 7a (%)
Reaction conditionsa
Static pyrolysis 255 ꢁC, 20 min
DABCO/xylene, 140 ꢁC, 24 h
DABCO/xylene, MW 190 ꢁC, 10 min
DABCO/THF, MW 190 ꢁC, 10 min
DABCO/DPE, oil bath 190–200 ꢁC, 40 min
DABCO/PhNO2, oil bath, 190 ꢁC, 10 min
DABCO/IL, oil bath, 140 ꢁC, 10 min
1
2
3
4
5
6
7
39
0
67
62
40
49
34
4. Experimental
4.1. General
a
Static pyrolysis was performed in a sealed tube as described in Section 4. All
other experiments were performed by mixing 4a (1 mmol), DABCO (2 mmol), xylene
or THF (5 mL) or DPE or PhNO2 or IL (0.5 mL). IL used was ethylpyridinium
tetrafluoroborate.
All melting points are uncorrected. IR spectra were recorded in
KBr disks on a Perkin Elmer System 2000 FT-IR spectrophotometer.
1H and 13C NMR spectra were recorded on a Bruker DPX 400,
400 MHz super-conducting NMR spectrometer. Mass spectra were
measured on VG Auto-spec-Q (high resolution, high performance,
tri-sector GC/MS/MS) and with LCMS using Agilent 1100 series LC/
MSD with an API-ES/APCI ionization mode. Microanalyses were
performed on LECO CH NS-932 Elemental Analyzer. The starting
compounds 10–12 were prepared as reported and the new de-
rivatives were prepared as described in this section.
O
R
R
HN
AcO
AcO
N
O
N
S
N
N
R
-CH3COOH
O
AcO
N
O
S
OAc
OAc
AcO
AcO
R
4a-c, e CH2Ar
5a, b, d Ar
7a-c, e CH2Ar
8a, b, d Ar
34-67%
63-88%
4.2. Synthesis of anhydrothioglycosyls 7–9: general
procedures
6a-c, e, f CH=CHAr
9a-c, e, f CH=CHAr 27-76%
Ar = a, C6H5, b, p-ClC6H4, c, p-CH3C6H4, d, p-CH3OC6H4, e, 2-thienyl, f, p-O2NC6H4
(A) A mixture of the appropriate derivatives 4–6 (1 mmol) and
DABCO (2 mmol) in xylene or THF (2 mL) was heated in the
microwave reaction tube for 10 min at 190 ꢁC. The content of
the tube was washed with petroleum ether and filtered. The
precipitate was collected, purified by boiling with ethanol and
charcoal, and recrystallized from ethanol.
Scheme 2.
The starting materials 4–6 used in this investigation have been
prepared as outlined in Scheme 3. Thus, reacting the appropriate 4-
amino-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-ones 10–12 with
acetobromoglucose in DMF and triethylamine afforded the corre-
sponding 2-tetra-O-acetyl-
b
-
D
-glucopyranosyl derivatives 13–15.
(B) A mixture of the appropriate derivatives 4–6 (1 mmol), DABCO
(2 mmol), and DPE (0.5 mL) was heated at 190–200 ꢁC (oil
bath) for 40 min. The contents of tube were washed with pe-
troleum ether and the precipitate was collected, purified by
The latter were readily deaminated upon treatment with nitrous
acid in acetic acid to afford the corresponding 2-glucosyl de-
rivatives 4–6.

8208
I.A. Al-Juwaiser et al. / Tetrahedron 64 (2008) 8206–8212
boiling with ethanol and charcoal, and recrystallized from
ethanol.
12.4, 4.6), 4.69 (dd,1H, J 5.5, 3.6), 5.39 (t,1H, J 9.7), 5.51 (dd,1H, J 9.4,
5.7), 5.73 (d, 1H, J 3.7), 6.97 (dd, 1H, J 4.8, 3.5), 7.02 (d, 1H, J 3.5), 7.21
(d, 1H, J 4.8). Anal. Calcd for C20H21N3O8S2 (495.5): C 48.48; H 4.27;
N 8.48; S 12.94. Found: C 48.39; H 4.20; N 8.29; S 12.94.
(C) A mixture of 4a (1 mmol), DABCO (2 mmol), and ethyl-
pyridinium tetrafluoroborate (0.1 g) was heated at 140 ꢁC (oil
bath) for 10 min. The contents of tube were washed with water
and filtered. After drying, the product was dissolved in CDCl3
and the yield was determined by 1H NMR spectroscopy.
(D) Compound 4a (1 mmol) was introduced in the reaction tube
(1.5ꢂ12 cm Pyrex), cooled in liquid nitrogen, sealed under
vacuum (0.06 mbar), and placed in the pyrolyzer heated at
255 ꢁC (static pyrolyzer) for 20 min. The contents of the tube
were then dissolved in CDCl3 and the yield was determined by
1H NMR spectroscopy.
4.2.5. 3,2-Anhydro-6-phenyl-2(3,4,6-tri-O-acetyl-b-D-
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 8a
Colorless needles, yield 63% (A), 87% (B), mp 235–237 ꢁC. LCMS:
m/z¼476 (Mþ1). IR: 3059, 2958, 1751, 1659, 1553, 1507, 1488, 1416,
1371, 1240, 1111, 1064. 1H NMR (CDCl3):
d 2.10, 2.11, 2.16 (3s, 9H,
3CH3CO), 3.87 (ddd, 1H, J 9.8, 4.5, 2.2), 4.16 (dd, 1H, J 12.6, 2.2), 4.39
(dd, 1H, J 12.6, 4.5), 4.79 (dd, 1H, J 5.8, 3.7), 5.44 (t, 1H, J 9.7), 5.56
(dd, 1H, J 9.5, 5.8), 5.85 (d, 1H, J 3.7), 7.48 (m, 3H), 8.10 (m, 2H). 13
C
(E) A mixture of the appropriate derivatives 4–6 (1 mmol), DABCO
(2 mmol), and PhNO2 (0.3 mL) was heated at 190 ꢁC (oil bath)
for 40 min. The contents of tube were washed with petroleum
ether and the precipitate was collected, purified by boiling with
ethanol and charcoal, and recrystallized from ethanol.
NMR (CDCl3):
d 20.5, 20.6, 20.7, 47.0, 61.4, 64.9, 69.4, 72.8, 89.1,
128.3, 129.0, 131.0, 131.4, 148.6, 159.7, 167.0, 169.3, 169.7, 170.6. Anal.
Calcd for C21H21N3O8S (475.5): C 53.05; H 4.45; N 8.84; S 6.74.
Found: C 52.88; H 4.50; N 8.89; S 6.94.
4.2.6. 3,2-Anhydro-6-p-chlorophenyl-2(3,4,6-tri-O-acetyl-b-D-
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 8b
Colorless needles, yield 75% (A), 65% (B), mp 237–238 ꢁC. LCMS:
m/z¼510 (Mþ1), 511 (Mþ2). IR: 2975, 2959, 2930, 2908, 1755, 1657,
1549, 1503, 1486, 1418, 1372, 1220, 1112, 1094, 1064. 1H NMR
4.2.1. 3,2-Anhydro-6-benzyl-2(3,4,6-tri-O-acetyl-b-D-
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 7a
Colorless needles, yield 67% (A), 40% (B), 34% (C), 39% (D), 49%
(E), mp 212–213 ꢁC. LCMS: m/z¼490 (Mþ1); MS: m/z¼489 (Mþ,
100%). IR: 3030, 2937, 1758, 1732, 1665, 1515, 1369, 1238, 1106, 1059.
(CDCl3): d 2.10, 2.11, 2.16 (3s, 9H, 3CH3CO), 3.88 (ddd, 1H, J 10.6, 4.8,
2.0), 4.16 (dd, 1H, J 12.4, 1.6), 4.39 (dd, 1H, J 12.6, 4.4), 4.79 (dd, 1H, J
5.4, 3.9), 5.44 (t, 1H, J 9.7), 5.56 (dd, 1H, J 9.5, 5.8), 5.85 (d, 1H, J 3.6),
1H NMR (CDCl3):
d 2.09, 2.12, 2.13 (3s, 9H, 3CH3CO), 3.81 (m, 1H),
7.43 (d, 2H, J 8.5), 8.11 (d, 2H, J 8.5). 13C NMR (CDCl3):
d 20.5, 20.6,
3.88 (d, 1H, J 14.3), 4.10 (d, 1H, J 14.3), 4.14 (dd, 1H, J 12.5, 2.0), 4.38
(dd, 1H, J 12.5, 4.7), 4.67 (dd, 1H, J 5.7, 3.4), 5.40 (t, 1H, J 9.6), 5.50
(dd, 1H, J 9.5, 5.8), 5.71 (d, 1H, J 3.6), 7.28 (t, 2H, J 8.0), 7.32 (t, 1H, J
20.7, 47.0, 61.3, 64.9, 69.4, 72.8, 89.1, 128.6, 129.8, 130.3, 137.3, 147.4,
159.5, 167.0, 169.3, 169.7, 170.6. Anal. Calcd for C21H20ClN3O8S
(509.9): C 49.46; H 3.95; N 8.24; S 6.29. Found: C 49.38; H 3.95; N
8.40; S 6.23.
7.6), 7.37 (d, 2H, J 8.0). 13C NMR (CDCl3):
d 20.5, 20.6, 20.7, 36.7, 46.9,
61.4, 65.0, 69.4, 72.6, 88.9, 127.0, 128.5, 129.5, 153.1, 153.4, 160.2,
168.0, 169.2, 169.7, 170.6. Anal. Calcd for C22H23N3O8S (489.5): C
53.98; H 4.74; N 8.58; S 6.55. Found: C 54.18; H 4.68; N 8.71; S 6.25.
4.2.7. 3,2-Anhydro-6-p-methoxyphenyl-2(3,4,6-tri-O-acetyl-b-D-
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 8d
Colorless needles, yield 68% (A), 88% (B), mp 218–219 ꢁC. MS:
m/z¼505(Mþ,15%). IR:3077, 2974, 2940, 2840,1756,1725,1671,1607,
1547,1499,1369,1249,1232,1107,1084,1065,1047. 1H NMR (CDCl3):
4.2.2. 3,2-Anhydro-6-p-chlorobenzyl-2(3,4,6-tri-O-acetyl-b-D-
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 7b
Colorless plates, yield 58% (A), 63% (B), mp 249–250 ꢁC. LCMS:
m/z¼524 (Mþ1). MS: m/z¼523 (Mþ, 100%). IR: 2919, 2851, 1760,
d
2.09, 2.11, 2.15 (3s, 9H, 3CH3CO), 3.85 (m, 1H), 3.88 (s, 3H, OCH3),
1731, 1665, 1518, 1234. 1H NMR (CDCl3):
d 2.09, 2.12, 2.13 (3s, 9H,
4.16 (dd, 1H, J 2.0, 12.6), 4.39 (dd, 1H, J 12.5, 4.5), 4.77 (dd, 1H, J 5.6,
3.8), 5.44 (t, 1H, J 9.6), 5.55 (dd, 1H, J 9.5, 5.8), 5.82 (d, 1H, J 3.6), 6.97
3CH3CO), 3.83 (m, 1H), 3.84 (d, 1H, J 14.5), 4.05 (d, 1H, J 14.6), 4.16
(dd, 1H, J 12.5, 2.0), 4.38 (dd, 1H, J 12.6, 4.6), 4.68 (dd, 1H, J 5.6, 3.7),
5.39 (t, 1H, J 9.7), 5.50 (dd, 1H, J 9.5, 5.8), 5.72 (d, 1H, J 3.5), 7.29 (s,
(d, 2H, J 8.8), 8.16 (d, 2H, J 8.8). 13C NMR (CDCl3):
d 20.5, 20.6, 20.7,
47.0, 55.4, 61.4, 65.0, 69.5, 72.7, 89.2, 113.7, 123.8, 130.8, 147.9, 159.9,
161.9, 166.4, 169.2, 169.7, 170.6. Anal. Calcd for C22H23N3O9S (505.5):
C 52.27; H 4.59; N 8.31; S 6.34. Found: C 52.29; H 4.56; N 8.41; S 6.27.
4H). 13C NMR (CDCl3):
d 20.5, 20.6, 20.7, 36.1, 46.9, 61.3, 65.0, 69.4,
72.6, 88.9, 128.7, 130.9, 132.9, 133.8, 152.7, 160.1, 168.2, 169.2, 169.6,
170.6. Anal. Calcd for C22H22ClN3O8S (523.9): C 50.43; H 4.23; N
8.02; S 6.12. Found: C 50.29; H 4.22; N 8.20; S 6.17.
4.2.8. 3,2-Anhydro-6-styryl-2-(3,4,6-tri-O-acetyl-b-D-
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 9a
Gray plates, yield 68% (A), 27% (E), mp 214–215 ꢁC. MS: m/z¼501
4.2.3. 3,2-Anhydro-6-p-methylbenzyl-2(3,4,6-tri-O-acetyl-b-D-
(Mþ, 35%). IR: 3063, 2919, 1753, 1235, 1222. 1H NMR (CDCl3):
d 2.10,
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 7c
Colorless needles, yield 67% (A), 55% (B), mp 218–219 ꢁC. LCMS:
2.12, 2.15 (3s, 9H, 3CH3CO), 3.88 (ddd, 1H, J 9.6, 4.2, 2.2), 4.18 (dd,
1H, J 12.6, 2.1), 4.40 (dd, 1H, J 12.6, 4.4), 4.77 (dd, 1H, J 5.6, 3.7), 5.44
(t, 1H, J 9.6), 5.55 (dd, 1H, J 9.6, 5.6), 5.80 (d, 1H, J 4.0), 7.17 (d, 1H, J
16.4), 7.39 (m, 3H), 7.59 (d, 2H, J 6.4), 8.10 (d, 1H, J 16.4). 13C NMR
m/z¼504 (Mþ1); MS: m/z¼503.7 (Mþ, 100%). IR: 3029, 2949, 1761,
1732, 1664, 1516, 1234, 1061. 1H NMR (CDCl3):
d 2.09, 2.12, 2.13 (3s,
9H, 3CH3CO), 2.34 (s, 3H, CH3), 3.82 (m, 2H), 4.07 (d, 1H, J 14.4), 4.16
(dd, 1H, J 12.4, 2.4), 4.37 (dd, 1H, J 12.4, 4.8), 4.66 (dd, 1H, J 5.6, 4.0),
5.40 (t,1H, J 9.6), 5.50 (dd,1H, J 9.6, 6.0), 5.71 (d,1H, J 3.6), 7.13 (d, 2H,
(CDCl3):
d 20.5, 20.6, 20.7, 47.0, 61.4, 65.0, 69.5, 72.8, 89.3, 119.0,
127.8, 128.8, 129.6, 135.9, 139.8, 147.2, 160.0, 166.6, 169.3, 169.7,
170.6. Anal. Calcd for C23H23N3O8S (501.5): C 55.08; H 4.62; N 8.38;
S 6.39. Found: C 55.09; H 4.56; N 8.41; S 6.27. HRMS¼501.1201
(C23H23O8N3S requires 501.1200).
J 8.0), 7.26 (d, 2H, J 8.0). 13C NMR (CDCl3):
d 21.1, 21.2, 21.3, 21.7, 36.9,
47.5, 62.0, 65.6, 70.0, 73.2, 89.5, 129.9, 130.0, 132.9, 137.3, 153.9,
160.8,168.6,169.8,170.3,171.2. Anal. Calcd for C23H25N3O8S (503.5):
C 54.86; H 5.00; N 8.35; S 6.37. Found: C 54.80; H 4.98; N 8.45; S 6.38.
4.2.9. 3,2-Anhydro-p-chlorostyryl-2-(3,4,6-tri-O-acetyl-b-D-
4.2.4. 3,2-Anhydro-6-(2-thienylmethyl)-2-(3,4,6-tri-O-acetyl-b-D-
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 9b
Colorless needles, yield 52% (A), 66% (B), mp 243–245 ꢁC. MS:
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 7e
m/z¼535 (Mþ, 40%). IR: 3063, 2922, 1750, 1643, 1233, 1222, 1109,
Colorless plates, yield 34% (A), mp 170–172 ꢁC. LCMS: m/z¼496
(Mþ1). IR: 3105, 2958, 1750, 1663, 1639, 1511, 1229, 1057. 1H NMR
1078. 1H NMR (CDCl3):
d 2.10, 2.12, 2.16 (3s, 9H, 3CH3CO), 3.87 (ddd,
(CDCl3): d 2.09, 2.12, 2.14 (3s, 9H, 3CH3CO), 3.84 (m, 1H), 4.10 (d, 1H,
1H, J 9.5, 4.0, 2.5), 4.19 (dd, 1H, J 12.5, 2.0), 4.40 (dd, 1H, J 12.6, 4.4),
4.76 (dd, 1H, J 5.6, 3.7), 5.44 (t, 1H, J 9.7), 5.55 (dd, 1H, J 9.5, 5.9), 5.79
J 15.4), 4.16 (dd, 1H, J 12.3, 2.4), 4.32 (d, 1H, J 15.5), 4.37 (dd, 1H, J

I.A. Al-Juwaiser et al. / Tetrahedron 64 (2008) 8206–8212
8209
(d, 1H, J 3.6), 7.12 (d, 1H, J 16.3), 7.38 (d, 2H, J 8.4), 7.52 (d, 2H, J 8.4),
8.07 (d,1H, J 16.3).13C NMR (CDCl3):
20.5, 20.6, 20.7, 46.9, 61.3, 64.9,
69.4, 72.8, 89.2, 119.6, 128.8, 129.1, 134.4, 135.4, 138.3, 146.9, 159.9,
166.7, 169.2, 169.7, 170.6. Anal. Calcd for C23H22N3O8SCl (536.0): C
51.54; H 4.14; N 7.84; S 5.98. Found: C 51.35; H 4.30; N 7.73; S 5.86.
4.3.2. 4-Amino-6-p-chlorobenzyl-2-(2,3,4,6-tetra-O-acetyl-b-D-
d
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 13b
Colorless plates, yield 75%, mp 125 ꢁC. LCMS: m/z¼599 (Mþ1).
1H NMR (CDCl3):
d 1.91, 2.07, 2.09, 2.10 (4s, 12H, 4CH3CO), 3.90 (d,
1H, J 13.2), 3.96 (m, 1H), 4.05 (d, 1H, J 13.6), 4.18 (d, 1H, J 12.4), 4.29
(dd, 1H, J 12.6, 5.0), 5.25 (t, 1H, J 9.8), 5.41 (t, 1H, J 9.4), 5.87 (t, 1H, J
9.4), 6.32 (s, 2H, NH2), 6.71 (d, 1H, J 9.4), 7.13 (m, 4H). 13C NMR
4.2.10. 3,2-Anhydro-6-p-methylstyryl-2-(3,4,6-tri-O-acetyl-b-D-
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 9c
(CDCl3): d 20.6 (2C), 20.7, 20.8, 36.9, 61.6, 67.7, 68.6, 73.9, 74.6, 87.2,
Gray plates, yield 76% (A), 27% (E), mp 263–264 ꢁC. LCMS:
128.8, 130.9, 133.3, 133.5, 145.5, 146.8, 169.0, 169.5, 169.9, 170.2,
170.6. Anal. Calcd for C24H27ClN4O10S (599.0): C 48.12; H 4.54; N
9.35; S 5.35. Found: C 48.05; H 4.42; N 9.27; S 5.20.
m/z¼516 (Mþ1). IR: 3075, 2927, 1759, 1737, 1675, 1538, 1506, 1409,
1238, 1211, 1109, 1094, 1055. 1H NMR (CDCl3):
d 2.09, 2.12, 2.15 (3s,
9H, 3CH3CO), 2.39 (s, 3H, CH3), 3.87 (ddd,1H, J 9.8, 4.3, 2.3), 4.18 (dd,
1H, J 12.6, 2.1), 4.39 (dd, 1H, J 12.6, 4.4), 4.67 (dd, 1H, J 5.7, 3.8), 5.43
(t, 1H, J 9.7), 5.55 (dd, 1H, J 9.6, 5.8), 5.80 (d, 1H, J 3.7), 7.12 (d, 1H, J
4.3.3. 4-Amino-6-p-methylbenzyl-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 13c
Colorless needles, yield 65%, mp 168–169 ꢁC. MS: m/z¼578 (Mþ,
16%). IR: 3431, 3305, 2998, 1748, 1708, 1547, 1429, 1368, 1285, 1242,
16.4), 7.21 (d, 2H, J 8.0), 7.49 (d, 2H, J 8.0), 8.06 (d, 1H, J 16.4). 13
C
NMR (CDCl3): d 20.5, 20.6, 20.7, 21.4, 46.9, 61.3, 65.0, 69.4, 72.7, 89.2,
117.8, 127.7, 129.6, 133.1, 139.6, 140.0, 147.3, 160.0, 166.5, 169.2, 169.7,
170.6. Anal. Calcd for C24H25N3O8S (515.6): C 55.92; H 4.89; N 8.15; S
6.22. Found: C 55.89; H 4.94; N 8.22; S 6.20.
1099, 1063, 906. 1H NMR (CDCl3):
d 1.92, 2.08, 2.09, 2.11 (4s, 12H,
4CH3CO), 2.33 (s, 3H, CH3), 3.90 (d, 1H, J 13.5), 3.96 (ddd, 1H, J 9.8,
4.6, 1.8), 4.04 (d, 1H, J 13.5), 4.18 (d, 1H, J 12.2), 4.28 (dd, 1H, J 12.6,
5.0), 5.26 (t, 1H, J 9.8), 5.41 (t, 1H, J 9.4), 5.90 (t, 1H, J 9.4), 6.30 (s, 2H,
NH2), 6.71 (d, 1H, J 9.4), 7.13 (d, 2H, J 7.8), 7.27 (d, 2H, J 8.2). 13C NMR
4.2.11. 3,2-Anhydro-6-[2-(2-thienyl)vinyl]-2-(3,4,6-tri-O-acetyl-
b-
D
-mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 9e
(CDCl3): d 20.6 (2C), 20.7, 20.8, 21.1, 36.6, 61.6, 67.7, 68.6, 73.9, 74.6,
Yellow plates, yield 55% (A), 60% (B), mp 274–276 ꢁC. MS:
87.2, 129.3, 129.4, 131.8, 137.0, 146.2, 146.8, 169.0, 169.4, 169.9, 170.3,
170.6. Anal. Calcd for C25H30N4O10S (578.6): C 51.90; H 5.23; N 9.68;
S 5.54. Found: C 51.75; H 5.22; N 9.57; S 5.39.
m/z¼507 (Mþ, 15%). IR: 2977, 2937, 1754, 1670, 1619, 1543, 1504,
1368, 1236, 1218, 1107, 1058. 1H NMR (CDCl3):
d 2.09, 2.12, 2.15 (3s,
9H, 3CH3CO), 3.87 (ddd, 1H, J 9.8, 4.3, 2.2), 4.18 (dd, 1H, J 12.6, 2.2),
4.39 (dd, 1H, J 12.6, 4.4), 4.76 (dd, 1H, J 5.7, 3.7), 5.43 (t, 1H, J 9.7),
5.55 (dd,1H, J 9.6, 5.8), 5.78 (d,1H, J 3.8), 6.91 (d,1H, J 16.0), 7.07 (dd,
1H, J 5.0, 3.6), 7.26 (d, 1H, J 3.6), 7.37 (d, 1H, J 5.0), 8.34 (d, 1H, J 16.0).
4.3.4. 4-Amino-6-(2-thienylmethyl)-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 13e
Gray plates, yield 79%, mp 142–143 ꢁC. MS: m/z¼570 (Mþ, 16%).
IR: 3110, 2939, 1755, 1692, 1437, 1381, 1291, 1237, 1089, 1040. 1H
13C NMR (CDCl3):
d 20.5, 20.6, 20.7, 46.9, 61.4, 65.0, 69.4, 72.8, 89.3,
118.5, 127.7, 128.1, 129.9, 133.1, 141.7, 147.0, 159.9, 166.3, 169.2, 169.7,
170.6. Anal. Calcd for C21H21N3O8S2 (507.5): C 49.70; H 4.17; N 8.28;
S 12.63. Found: C 49.90; H 4.22; N 8.27; S 12.60.
NMR (CDCl3): d 1.91, 2.06, 2.08, 2.10 (4s, 12H, 4CH3CO), 3.96 (ddd,
1H, J 9.7, 5.4, 2.9), 4.17 (m, 2H), 4.27 (m, 2H), 5.24 (t, 1H, J 9.8), 5.40
(t, 1H, J 9.5), 5.83 (t, 1H, J 9.4), 6.35 (s, 2H, NH2), 6.69 (d, 1H, J 9.4),
6.96 (dd, 1H, J 4.8, 3.5), 7.04 (d, 1H, J 3.5), 7.21 (d, 1H, J 4.8). 13C NMR
4.2.12. 3,2-Anhydro-6-p-nitrostyryl-2-(3,4,6-tri-O-acetyl-
b
-D-
(CDCl3): d 20.5 (2C), 20.6, 20.7, 31.0, 61.5, 67.7, 68.6, 73.8, 74.5, 87.2,
mannopyranosyl)-3-mercapto-1,2,4-triazin-5(2H)-one 9f
125.3,127.1,127.4,136.1,144.7,146.6,168.9,169.4,169.9,170.2, 170.5.
HRMS¼570.1085 (C22H26O10N4S2 requires 570.1084).
Yellow plates, yield 57% (A), 46% (B), mp 229–230 ꢁC. LCMS:
m/z¼547 (Mþ1). IR: 2967, 2938, 1751, 1680, 1628, 1546, 1505, 1342,
1236, 1219, 1109, 1057. 1H NMR (CDCl3):
d
2.07, 2.08, 2.12 (3s, 9H,
4.3.5. 4-Amino-6-phenyl-2-(2,3,4,6-tetra-O-acetyl-b-D-
3CH3CO), 3.89 (m, 1H), 4.19 (dd, 1H, J 12.6, 1.7), 4.33 (dd, 1H, J 9.6,
4.1), 4.79 (dd, 1H, J 5.4, 3.9), 5.44 (t, 1H, J 9.7), 5.56 (dd, 1H, J 9.5, 5.8),
5.83 (d, 1H, J 3.6), 7.24 (d, 1H, J 16.4), 7.73 (d, 2H, J 8.6), 8.20 (d, 1H, J
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 14a
Yellow plates, yield 54%, mp 168–169 ꢁC (lit.11a mp 174 ꢁC). 1H
NMR (CDCl3): d 1.97, 2.08, 2.09 (s, 3H, s, 6H, s, 3H, 4CH3CO), 4.00 (m,
16.4), 8.26 (d, 2H, J 8.6). 13C NMR (CDCl3):
d
20.5, 20.6, 20.7, 47.0,
61.6, 64.9, 69.4, 72.9, 89.2, 118.1, 124.2, 128.1, 128.3, 135.4, 137.1,
142.2, 147.9, 159.7, 166.9, 169.6, 170.5. Anal. Calcd for C23H22N4O10
1H), 4.18 (dd, 1H, J 12.5, 2.0), 4.28 (dd, 1H, J 12.5, 5.0), 5.24 (t, 1H, J
9.8), 5.45 (t,1H, J 9.5), 5.97 (t,1H, J 9.4), 6.51 (s, 2H, NH2), 6.86 (d,1H,
J 9.4), 7.52 (m, 3H), 8.14 (m, 2H).
S
(546.5): C 50.55; H 4.06; N 10.25; S 5.87. Found: C 50.50; H 4.02; N
10.16; S 5.80.
4.3.6. 4-Amino-6-p-chlorophenyl-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 14b
Colorless plates, yield 78%, mp 171–172 ꢁC. MS: m/z¼584 (Mþ,
15%). IR: 3335, 3228, 2958, 1753, 1741, 1693, 1435, 1368, 1231, 1061,
4.3. 4-Amino-6-substituted-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-
ones 13–15: general procedure
1034. 1H NMR (CDCl3):
d 1.97, 2.08, 2.09 (s, 3H, s, 6H, s, 3H, 4CH3CO),
4.00 (m,1H), 4.18 (d,1H, J 12.3), 4.29 (dd,1H, J 12.4, 5.0), 5.25 (t,1H, J
9.8), 5.46 (t,1H, J 9.4), 5.96 (t,1H, J 9.4), 6.51 (s, 2H, NH2), 6.85 (d,1H,
A mixture of 10–12 (10 mmol) and 2,3,4,6-O-tetraacetyl-a-D-
glucopyranosyl bromide (4.2 g, 11 mmol) in DMF (5 ml) and tri-
ethylamine (1.0 mL) was stirred at room temperature overnight.
After dilution with water (20 mL), the precipitate was collected,
washed with water several times, and recrystallized from ethanol
into crystals of compounds 13–15.
J 9.3), 7.49 (d, 2H, J 8.4), 8.15 (d, 2H, J 8.4). 13C NMR (CDCl3):
d 20.06
(2C), 20.064, 20.7, 61.6, 67.7, 68.6, 73.8, 74.7, 87.4, 128.9, 129.1, 130.1,
137.6, 140.7, 146.5, 169.1 (2C), 169.5, 170.1, 170.6. HRMS¼584.0975
(C23H25ClN4O10S requires 584.0974).
4.3.7. 4-Amino-6-p-methoxyphenyl-2-(2,3,4,6-tetra-O-acetyl-
4.3.1. 4-Amino-6-benzyl-2-(2,3,4,6-tetra-O-acetyl-
b-
D-
b-D-glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 13a
one 14d
Yellow needles, yield 77%, mp 140 ꢁC (lit.11a mp 143 ꢁC). 1H NMR
Yellow plates, yield 80%, mp 133–134 ꢁC. MS: m/z¼580 (Mþ,
(CDCl3):
d
1.90, 2.07, 2.09, 2.10 (4s, 12H, 4CH3CO), 3.96 (m, 2H), 4.05
45%). IR: 3322, 3222, 2939, 1752, 1691, 1606, 1515, 1437, 1239, 1183,
(d, 1H, J 13.6), 4.18 (d, 1H, J 12.4), 4.28 (dd, 1H, J 12.6, 5.0), 5.25 (t, 1H,
J 9.8), 5.40 (t, 1H, J 9.4), 5.88 (t, 1H, J 9.3), 6.31 (s, 2H, NH2), 6.70 (d,
1H, J 9.4), 7.29 (m, 5H).
1062, 1034. 1H NMR (CDCl3):
d 1.97, 2.07, 2.08, 2.09 (4s, 12H,
4CH3CO), 3.90 (s, 3H, CH3), 4.00 (ddd, 1H, J 10.0, 5.0, 2.2), 4.18 (dd,
1H, J 12.6, 2.2), 4.29 (dd, 1H, J 12.6, 5.0), 5.25 (t, 1H, J 9.8), 5.45 (t, 1H,

8210
I.A. Al-Juwaiser et al. / Tetrahedron 64 (2008) 8206–8212
J 9.4), 5.99 (t, 1H, J 9.4), 6.50 (s, 2H, NH2), 6.84 (d, 1H, J 9.4), 7.03 (d,
2H, J 8.9), 8.19 (d, 2H, J 8.9). 13C NMR (CDCl3):
20.56 (2CH3), 20.6,
20.7, 55.4, 61.6, 67.7, 68.6, 73.9, 74.6, 87.4, 114.0, 123.1, 130.5, 141.5,
146.7, 162.0, 169.1 (2C), 169.4, 170.2, 170.6. Anal. Calcd for
reaction mixture was then stirred at room temperature overnight.
After dilution with cold ice/water mixture (20 g), the precipitate
was collected and crystallized from ethanol.
d
C
24H28N4O11S (580.6): C 49.65; H 4.86; N 9.65; S 5.52. Found: C
4.4.1. 6-Benzyl-2-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-2,3-
49.56; H 5.02; N 9.56; S 5.46.
dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 4a
Yellow plates, yield 87%, mp 158–160 ꢁC (lit.11a mp 162 ꢁC).
4.3.8. 4-Amino-6-styryl-2-(2,3,4,6-tetra-O-acetyl-
b
-
D
-
LCMS: m/z¼550 (Mþ1). IR: 3243, 3182, 3029, 2987, 1754, 1707,
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 15a
1489, 1371, 1252, 1228, 1078, 1044. 1H NMR (CDCl3):
d 1.95, 2.07,
Yellow plates, yield 80%, mp 183–185 ꢁC (lit.11c mp 180 ꢁC). 1H
2.09, 2.12 (4s, 12H, 4CH3CO), 3.89 (d, 1H, J 13.6), 3.95 (m, 1H), 4.02
(d, 1H, J 13.6), 4.19 (d, 1H, J 11.2), 4.30 (dd, 1H, J 12.6, 4.9), 5.2 (t, 1H J
9.8), 5.4 (t, 1H, J 9.2), 5.8 (t, 1H, J 9.3), 6.7 (d, 1H, J 9.3), 7.3 (m, 5H),
NMR (CDCl3): d 1.96, 2.08, 2.09 (s, 3H, s, 3H, s, 6H, 4CH3CO), 4.01 (m,
1H), 4.19 (d,1H, J 12.4), 4.31 (dd,1H, J 12.6, 5.0), 5.28 (t,1H, J 9.8), 5.44
(t,1H, J 9.4), 5.98 (t,1H, J 9.4), 6.44 (s, 2H, NH2), 6.72 (d,1H, J 9.4), 7.16
(d, 1H, J 16.4), 7.41 (m, 3H), 7.65 (d, 2H, J 7.0), 7.98 (d, 1H, J 16.4).
9.40 (s, 1H, NH). 13C NMR (CDCl3):
d 20.56 (2C), 20.6, 20.7, 36.3, 61.5,
67.6, 68.6, 73.8, 74.5, 85.8, 127.3, 128.7, 129.5, 133.0, 150.1, 150.3,
169.1, 169.4, 170.2, 170.6, 174.7.
4.3.9. 4-Amino-6-p-chlorostyryl-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 15b
4.4.2. 6-p-Chlorobenzyl-2-(2,3,4,6-tetra-O-acetyl-b-D-
Yellow plates, yield 60%, mp 238–239 ꢁC (lit.11c,d mp 240–
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 4b
Colorless plates, yield 85%, mp 134–136 ꢁC. LCMS: m/z¼585
(Mþ1). IR: 3243, 2949, 1754, 1709, 1489, 1371, 1250, 1226, 1043. 1H
242 ꢁC). 1H NMR (CDCl3):
d 1.97, 2.08, 2.10 (s, 3H, s, 3H, s, 6H,
4CH3CO), 3.40 (m, 1H), 4.19 (d, 1H, J 12.8), 4.31 (dd, 1H, J 12.8, 5.2),
5.27 (t, 1H, J 9.8), 5.44 (t, 1H, J 9.4), 5.97 (t, 1H, J 9.4), 6.42 (s, 2H,
NH2), 6.72 (d, 1H, J 9.2), 7.12 (d, 1H, J 16.6), 7.39 (d, 2H, J 8.0), 7.58 (d,
2H, J 8.0), 7.93 (d, 1H, J 16.6).
NMR (CDCl3): d 1.94, 2.02, 2.06, 2.10 (4s, 12H, 4CH3CO), 3.84 (d, 1H, J
6.8), 3.92 (m, 1H), 3.94 (d, 1H, J 5.2), 4.18 (d, 1H, J 11.6), 4.29 (dd,1H, J
12.6, 4.7), 5.23 (t, 1H, J 9.8), 5.40 (t, 1H, J 9.5), 5.77 (t, 1H, J 9.4), 6.67
(d, 1H, J 9.3), 7.30 (m, 4H), 10.57 (s, 1H, NH). 13C NMR (CDCl3):
4.3.10. 4-Amino-6-p-methylstyryl-2-(2,3,4,6-tetra-O-acetyl-
b-D
-
d 20.56 (2C), 20.6, 20.7, 35.7, 61.5, 67.6, 68.7, 73.7, 74.5, 85.8, 128.8,
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 15c
Yellow plates, yield 75%, mp 244–245 ꢁC. MS: m/z¼590 (Mþ,
75%). IR: 3225, 3170, 2936, 1753, 1725, 1243, 1185. 1H NMR (CDCl3):
130.9, 132.9, 133.3, 149.9, 150.3, 169.1, 169.4, 170.2, 170.6,174.6. Anal.
Calcd for C24H26ClN3O10S (584.0): C 49.36; H 4.49; N 7.20; S 5.49.
Found: C 49.29; H 4.43; N 7.19; S 5.44.
d
1.96, 2.08, 2.10 (s, 3H, s, 3H, s, 6H, 4CH3CO), 2.41 (s, 3H, CH3), 3.99
(m, 1H), 4.19 (d, 1H, J 12.4), 4.31 (dd, 1H, J 12.7, 4.9), 5.28 (t,1H, J 9.7),
5.44 (t,1H, J 9.4), 5.97 (t,1H, J 9.4), 6.43 (s, 2H, NH2), 6.71 (d,1H, J 9.3),
7.11 (d, 1H, J 16.3), 7.23 (d, 2H, J 7.8), 7.56 (d, 2H, J 7.8), 7.96 (d, 1H, J
16.3). HRMS¼590.1677 (C26H30O10N4S requires 590.1677).
4.4.3. 6-p-Methylbenzyl-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 4c
Colorless plates, yield 75%, mp 170–172 ꢁC. LCMS m/z¼564
(Mþ1). IR: 3246, 2969, 1754, 1708, 1489, 1252, 1225, 1076, 1044. 1H
NMR (CDCl3):
d 1.96, 207, 2.09, 2.11 (4s, 12H, 4CH3CO), 2.33 (s, 3H,
4.3.11. 4-Amino-6-[2-(2-thienyl)vinyl]-2-(2,3,4,6-tetra-O-acetyl-
b-D-glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-
CH3), 3.85 (m, 3H), 4.19 (d, 1H, J 11.6), 4.29 (dd, 1H, J 12.0, 5.0), 5.25
(t,1H, J 9.6), 5.40 (t,1H, J 9.2), 5.80 (t,1H, J 9.1), 6.65 (d,1H, J 9.1), 7.13
(d, 2H, J 7.2), 7.26 (d, 2H, J 7.3), 9.75 (s, 1H, NH). 13C NMR (CDCl3):
one 15e
Yellow plates, yield 70%, mp 196–198 ꢁC. MS: m/z¼582 (Mþ,
d 20.56 (2C), 20.6, 20.7, 21.0, 36.0, 61.5, 67.6, 68.6, 73.8, 74.4, 85.8,
100%). IR: 3297, 3207, 2943,1753,1435,1367, 1277, 1238,1062, 1040.
129.3,129.4,131.4, 137.0, 150.3,150.5,169.1, 169.4, 170.2, 170.6,174.7.
Anal. Calcd for C25H29N3O10S (563.6): C 53.28; H 5.19; N 7.46; S 5.69.
Found: C 53.14; H 5.18; N 7.45; S 5.68.
1H NMR (CDCl3):
d 1.96, 2.08, 2.09, 2.10 (4s,12H, 4CH3CO), 3.99 (ddd,
1H, J 9.9, 4.8, 1.9), 4.19 (dd, 1H, J 12.5, 1.8), 4.31 (dd, 1H, J 12.6, 5.1),
5.28 (t,1H, J 9.8), 5.44 (t,1H, J 9.4), 5.94 (t,1H, J 9.4), 6.42 (s, 2H, NH2),
6.73 (d, 1H, J 9.4), 6.93 (d, 1H, J 16.1), 7.09 (dd, 1H, J 4.5, 3.5), 7.35 (d,
1H, J 3.5), 7.40 (d, 1H, J 4.5), 8.12 (d, 1H, J 16.1). 13C NMR (CDCl3):
4.4.4. 6-(2-Thienylmethyl)-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 4e
Brown plates, yield 78%, mp 122–124 ꢁC. MS: m/z¼555 (Mþ,
5%). IR: 3109, 2939, 1754, 1719, 1477, 1370, 1238, 1038. 1H NMR
d
20.61 (2C), 20.6, 20.8, 61.6, 67.8, 68.5, 73.9, 74.7, 87.6, 116.3, 128.0,
128.2,130.3,132.0,140.9,141.4,146.7,168.8,168.9,169.5,170.2,170.6.
HRMS¼582.1087 (C23H26O10N4S2 requires 582.1084).
(CDCl3): d 1.95, 2.08, 2.11, 2.12 (4s, 12H, 4CH3CO), 3.94 (ddd, 1H, 9.4,
4.4, 2.0), 4.11 (d, 1H, J 15.2), 4.17 (m, 2H), 4.28 (dd, 1H, J 12.4, 4.4),
5.23 (t, 1H, J 9.6), 5.40 (t, 1H, J 9.5), 5.74 (t, 1H, J 9.4), 6.65 (d, 1H, J
9.2), 6.96 (dd, 1H, J 4.8, 3.5), 7.02 (d, 1H, J 3.5), 7.21 (d, 1H, J 4.8),
4.3.12. 4-Amino-6-p-nitrostyryl-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 15f
Yellow plates, yield 65%, mp 264–266 ꢁC. MS: m/z¼621 (Mþ,
10.55 (s, 1H, NH). 13C NMR (CDCl3):
d 20.57 (2C), 20.6, 20.7, 30.3,
13%). IR: 2925, 1752, 1633, 1435, 1342, 1232. 1H NMR (CDCl3):
d
1.97,
61.5, 67.6, 68.7, 73.6, 74.4, 85.7, 125.4, 127.1, 127.5, 127.6, 135.8,
148.8, 150.5, 169.1, 170.2, 170.7, 174.8. HRMS¼555.0973
(C22H25O10N3S2 requires 555.0975).
2.08, 2.10 (s, 3H, s, 3H, s, 6H, 4CH3CO), 4.01 (m, 1H), 4.19 (dd, 1H, J
12.5, 1.6), 4.31 (dd,1H, J 12.6, 5.2), 5.27 (t,1H, J 9.8), 5.45 (t,1H, J 9.5),
5.96 (t, 1H, J 9.4), 6.45 (s, 2H, NH2), 6.73 (d, 1H, J 9.4), 7.29 (d, 1H, J
16.4), 7.79 (d, 2H, J 8.8), 8.03 (d,1H, J 16.4), 8.29 (d, 2H, J 8.8).13C NMR
4.4.5. 6-Phenyl-2-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-2,3-
(CDCl3):
d
20.56 (2C), 20.6, 20.7, 61.6, 67.7, 68.5, 73.8, 74.7, 87.6,121.4,
dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 5a
124.2,128.3,136.1,139.9,141.8,146.6,148.0,168.9,169.0,169.4,170.1,
170.5. HRMS¼621.1395 (C25H27O12N5S requires 621.1394).
Pale yellow plates, yield 90%, mp 157–158 ꢁC (lit.11a mp 160 ꢁC).
IR: 3240, 3063, 2940, 1753, 1716, 1478, 1428, 1371, 1285, 1230, 1111,
1037. 1H NMR (CDCl3):
d 2.02, 2.08, 2.085, 2.09 (4s, 12H, 4CH3CO),
4.4. 2-(2,3,4,6-Tetra-O-acetyl-
dihydro-3-thioxo-1,2,4-triazin-5(4H)-ones 4–6: general
procedure
b
-
D
-glucopyranosyl)-2,3-
4.00 (ddd, 1H, J 10.0, 4.8, 2.0), 4.19 (dd, 1H, J 12.4, 2.0), 4.30 (dd, 1H, J
12.4, 4.8), 5.24 (t, 1H, J 9.8), 5.45 (t, 1H, J 9.5), 5.89 (t, 1H, J 9.4), 6.79
(d, 1H, J 9.3), 7.51 (m, 3H), 8.11 (m, 2H), 9.74 (s, 1H, NH). 13C NMR
(CDCl3):
d 20.058 (2C), 20.6, 20.7, 61.5, 67.7, 68.7, 73.7, 74.6, 86.0,
To a solution of 13–15 (1 mmol) in acetic acid (5 mL) was added
128.6,128.8,130.1,131.5,145.9,150.2,169.2,169.5,170.1,170.6, 174.2.
sodium nitrite (0.2 g) with stirring over a period of 10 min. The
HRMS¼535.1257 (C23H25N3O10S requires 535.1255).

I.A. Al-Juwaiser et al. / Tetrahedron 64 (2008) 8206–8212
8211
4.4.6. 6-p-Chlorophenyl-2-(2,3,4,6-tetra-O-acetyl-
b-D
-
4.4.11. 6-[2-(2-Thienyl)vinyl]2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 5b
Yellow plates, yield 80%, mp 216–217 ꢁC. MS: m/z¼569 (Mþ,
12%). IR: 3220, 3163, 2946, 1752, 1720, 1595, 1579, 1483, 1424, 1400,
1369, 1289, 1259, 1230, 1190, 1092, 1063, 1040. 1H NMR (CDCl3):
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 6e
Yellow plates, yield 83%, mp 228–229 ꢁC. MS: m/z¼567 (Mþ,
34%). IR: 3550, 3420, 2941, 1752, 1715, 1489, 1245, 1194, 1044. 1H
NMR (CDCl3):
d 1.99, 2.08, 2.09, 2.12 (4s, 12H, 4CH3CO), 3.97 (ddd,
d
2.01, 2.08, 2.085, 2.09 (4s, 12H, 4CH3CO), 4.00 (ddd, 1H, J 10.4, 5.2,
1H, J 10.1, 4.9, 2.0), 4.19 (dd, 1H, J 12.6, 1.8), 4.33 (dd, 1H, J 12.6, 5.0),
5.27 (t, 1H, J 9.8), 5.43 (t, 1H, J 9.5), 5.85 (t, 1H, J 9.4), 6.68 (d, 1H, J
9.2), 6.88 (d,1H, J 16.1), 7.09 (dd,1H, J 5.0, 3.5), 7.34 (d,1H, J 3.5), 7.41
(d, 1H, J 5.0), 8.13 (d, 1H, J 16.1), 9.46 (s, 1H, NH). 13C NMR (CDCl3):
2.4), 4.20 (dd, 1H, J 12.0, 2.0), 4.31 (d, 1H, J 11.9), 5.25 (t, 1H, J 9.8),
5.45 (t, 1H, J 9.4), 5.87 (t, 1H, J 9.4), 6.77 (d, 1H, J 9.6), 7.47 (m, 2H),
8.12 (m, 2H), 9.82 (s, 1H, NH). 13C NMR (CDCl3):
d 20.6 (2C), 20.63,
20.7, 61.5, 67.7, 68.7, 73.6, 74.7, 86.0, 128.6, 128.9, 130.1, 137.9, 144.7,
150.2, 169.2, 169.5, 170.1, 170.6, 174.1. HRMS¼569.0867
(C23H24ClO10N3S requires 569.0865).
d 20.4 (3C), 20.5, 61.4, 67.6, 68.4, 73.6, 74.1, 85.5, 116.3, 127.6, 127.9,
129.9, 131.6, 141.3, 144.4, 151.3, 168.8, 169.2, 169.9, 170.4, 174.3.
HRMS¼567.0977 (C23H25N3O10S2 requires 567.0976).
4.4.7. 6-p-Methoxyphenyl-2-(2,3,4,6-tetra-O-acetyl-
b
-D
-
4.4.12. 6-p-Nitrostyryl-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 5d
Pale yellow crystals, yield 75%, mp 217–218 ꢁC. MS: m/z¼565
(Mþ, 50%). IR: 3217, 3166, 2947, 2908, 1751, 1714, 1606, 1284, 1256,
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 6f
Yellow plates, yield 75%, mp 239–240 ꢁC. MS: m/z¼606 (Mþ,
30%). IR: 3107, 2937, 1754, 1717, 1517, 1343, 1279, 1232, 1107, 1060,
1228, 1215, 1188, 1062, 1035.1H NMR (CDCl3):
d
2.00, 2.08, 2.09 (s,
1042. 1H NMR (CDCl3):
d 2.01, 2.08, 2.10, 2.11 (4s,12H, 4CH3CO), 3.99
3H, s, 3H, s, 6H, 4CH3CO), 3.89 (s, 3H, OCH3), 3.99 (m, 1H), 4.19 (dd,
1H, J 12.6,1.7), 4.31 (dd,1H, J 12.6, 4.6), 5.25 (t,1H, J 9.8), 5.44 (t,1H, J
9.4), 5.90 (t, 1H, J 9.4), 6.76 (d, 1H, J 9.3), 7.00 (d, 2H, J 9.0), 8.15 (d,
(ddd, 1H, J 10.1, 5.0, 2.1), 4.19 (dd, 1H, J 12.6, 2.0), 4.34 (dd, 1H, J 12.6,
5.1), 5.26 (t, 1H, J 9.8), 5.44 (t, 1H, J 9.5), 5.87 (t,1H, J 9.4), 6.69 (d, 1H,
J 9.3), 7.22 (d, 1H, J 16.4), 7.78 (d, 2H, J 8.8), 8.02 (d, 1H, J 16.4), 8.28
2H, J 9.0), 9.82 (s, 1H, NH). 13C NMR (CDCl3):
d
20.56 (2C), 20.6, 20.7,
55.4, 61.5, 67.7, 68.6, 73.7, 74.6, 86.0, 114.0, 122.7, 130.6, 145.3, 150.5,
162.2, 169.2, 169.5, 170.1, 170.6, 174.0. Anal. Calcd for C24H27N3O11
(d, 2H, J 8.8), 9.61 (s, 1H, NH). 13C NMR (DMSO-d6):
d 20.9, 21.0, 21.1,
21.6, 62.1, 68.1, 69.1, 73.3, 73.6, 85.4, 123.1, 124.7, 129.1, 135.1, 142.6,
144.6, 147.9, 152.0, 169.5, 170.0, 170.1, 170.6, 175.2. HRMS¼606.1263
(C25H26N4O12S requires 606.1262).
S
(565.6): C 50.97; H 4.81; N 7.43; S 5.67. Found: C 50.80; H 4.67; N
7.70; S 5.62.
4.5. 4-Amino-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-ones
4.4.8. 6-Styryl-2-(2,3,4,6-tetra-O-acetyl-
b
-D-glucopyranosyl)-2,3-
10–12: general procedure
dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 6a
Plate yellow crystals, yield 85%, mp 212–213 ꢁC (lit.11b mp
215 ꢁC). IR: 3061, 2920, 2850, 1753, 1714, 1382, 1371, 1231, 1060,
The appropriate a-ketoacid (10 mmol) was added slowly to a hot
solution of thiocarbohydrazide (10 mmol) in water (15 mL). The
reaction mixture was then heated under reflux for 10 min. After
cooling, the precipitate was collected, washed with cold water, and
recrystallized from DMF.
1041. 1H NMR (CDCl3):
d 1.99, 2.08, 2.09, 2.11 (4s,12H, 4CH3CO), 3.98
(m, 1H), 4.18 (d, 1H, J 12.1), 4.33 (dd, 1H, J 12.4, 4.5), 5.27 (t,1H, J 9.8),
5.43 (t, 1H, J 9.5), 5.88 (t, 1H, J 9.4), 6.64 (d, 1H, J 9.3), 7.10 (d, 1H, J
16.4), 7.41 (m, 3H), 7.64 (d, 2H, J 6.7), 7.99 (d, 1H, J 16.4), 9.40 (s, 1H,
NH). 13C NMR (CDCl3):
d
20.4, 20.5 (2C), 20.7, 61.5, 67.4, 68.9, 72.7,
4.5.1. 4-Amino-6-(2-thienylmethyl)-2,3-dihydro-3-thioxo-1,2,4-
triazin-5(4H)-one 10e
75.0, 89.7, 118.7, 127.9, 128.8, 129.7, 135.8, 140.4, 149.1, 150.9, 161.2,
168.7, 169.3, 170.1, 170.5.
Buff plates, yield 75%, mp 184–185 ꢁC. MS: m/z¼240 (Mþ, 100%).
IR: 3298, 3211, 3165, 3011, 3087, 2988, 1970, 1548, 1521, 1398, 1251,
4.4.9. 6-p-Chlorostyryl-2-(2,3,4,6-tetra-O-acetyl-
b
-D-
1238, 770, 690. 1H NMR (DMSO-d6):
d
4.11 (s, 2H, CH2), 6.51 (s, 2H,
NH2), 6.96 (br, 2H), 7.38 (br, 1H), 13.93 (s, 1H, NH). 13C NMR (DMSO-
d6): 30.9, 125.9, 127.5, 127.7, 138.4, 146.6, 148.9, 169.3.
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 6b
Yellow plates, yield 40%, mp 256–258 ꢁC (lit.11c,d mp 260 ꢁC).
LCMS: m/z¼596 (Mþ1). IR: 3055, 2922, 1750, 1629, 1233. 1H NMR
d
HRMS¼240.0132 (C8H8N4O10S2 requires 240.0134).
(CDCl3):
d 1.99, 2.08, 2.09, 2.11 (4s, 12H, 4CH3CO), 3.98 (ddd, 1H, J
10.0, 4.9, 2.0), 4.19 (dd, 1H, J 12.6, 2.0), 4.33 (dd, 1H, J 12.6, 5.1), 5.26
(t, 1H, J 9.8), 5.43 (t, 1H, J 9.5), 5.87 (t, 1H, J 9.4), 6.67 (d, 1H, J 9.3),
7.06 (d, 1H, J 16.4), 7.39 (d, 2H, J 8.4), 7.56 (d, 2H, J 8.4), 7.93 (d, 1H, J
d 21.2, 21.23, 21.3, 21.4,
62.2, 68.5, 69.3, 74.7, 75.0, 86.9, 119.4, 129.4, 129.6, 129.7, 135.2,
135.6, 137.3, 144.8, 155.5, 169.7, 170.1, 170.8, 171.3. Anal. Calcd for
4.5.2. 4-Amino-6-p-chlorophenyl-2,3-dihydro-3-thioxo-1,2,4-
triazin-5(4H)-one 11b
Pale yellow needles, yield 80%, mp 251–252 ꢁC. IR: 3299, 3206,
3083, 3039, 1662, 1557, 1538, 1510, 1404, 1391, 1327, 1248, 1239,
16.4), 9.75 (s, 1H, NH). 13C NMR (CDCl3):
1101, 863, 832. 1H NMR (DMSO-d6):
d
6.60 (s, 2H, NH2), 7.54 (d, 2H, J
8.0), 7.99 (d, 2H, J 8.0), 14.24 (s, 1H, NH). 13C NMR (DMSO-d6):
128.8, 130.2, 131.3, 135.3, 141.9, 148.5, 168.2. Anal. Calcd for
C
25H26ClN3O10S (596.0): C 50.38; H 4.40; N 7.05; S 5.38. Found: C
d
50.59; H 4.15; N 7.04; S 5.51.
C9H7ClN4OS (254.7): C 42.44; H 2.77; N 22.00; S 12.59. Found: C
42.50; H 2.89; N 22.00; S 12.62.
4.4.10. 6-p-Methylstyryl-2-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one 6c
Yellow plates, yield 77%, mp 243–245 ꢁC. MS: m/z¼575 (Mþ,
15%). IR: 3027, 2924, 1753, 1724, 1243, 1195, 1060, 1042. 1H NMR
4.5.3. 4-Amino-6-p-methylstyryl-2,3-dihydro-3-thioxo-1,2,4-
triazin-5(4H)-one 12c
Yellowplates,yield90%,mp271 ꢁC(lit.11e mp269–271 ꢁC).1HNMR
(CDCl3):
d
1.99, 2.08, 2.09, 2.11 (4s, 12H, 4CH3CO), 2.40 (s, 3H
(DMSO-d6):d2.33(s, 3H, CH3), 6.50 (s, 2H, NH2),7.07(d,1H,J16.4), 7.23
CH3), 3.98 (ddd, 1H, J 10.2, 5.1, 2.0), 4.20 (dd, 1H, J 12.5, 2.0), 4.33
(dd, 1H, J 12.6, 5.0), 5.27 (t, 1H, J 9.8), 5.43 (t, 1H, J 9.4), 5.88 (t,
1H, J 9.4), 6.67 (d, 1H, J 9.4), 7.06 (d, 1H, J 16.4), 7.22 (d, 2H, J 8.0),
7.54 (d, 2H, J 8.0), 7.96 (d, 1H, J 16.4), 9.61 (s, 1H, NH). 13C NMR
(d, 2H, J 7.7), 7.55 (d, 2H, J 7.7), 7.80 (d, 1H, J 16.4), 14.10 (s, 1H, NH).
4.5.4. 4-Amino-6-[2-(2-thienyl)vinyl]-2,3-dihydro-3-thioxo-1,2,4-
triazin-5(4H)-one 12e
(CDCl3):
d
20.6 (2C), 20.7, 20.8, 21.5, 61.5, 67.7, 68.5, 73.8, 74.6,
Yellow plates, yield 57%, mp 245–248 ꢁC. MS: m/z¼252 (Mþ,
86.2, 115.8, 127.9, 129.6, 132.9, 139.8, 140.3, 145.1, 150.5, 169.0,
169.5, 170.2, 170.6, 173.6. HRMS¼575.1565 (C26H29N3O10S requires
575.1568).
100%). IR: 3295, 3202, 3067, 1665, 1615, 1559, 1536, 1493, 1394,
1241, 1202, 750, 688. 1H NMR (DMSO-d6):
d
6.54 (s, 2H, NH2), 6.80
(d, 1H, J 16.2), 7.13 (dd, 1H, J 5.0, 4.0), 7.44 (d, 1H, J 4.0), 7.64 (d, 1H, J

8212
I.A. Al-Juwaiser et al. / Tetrahedron 64 (2008) 8206–8212
5.0), 8.00 (d, 1H, J 16.2), 14.13 (s, 1H, NH). 13C NMR (DMSO-d6):
118.9, 128.5, 129.1, 129.2, 130.4, 141.7, 141.8, 148.7, 167.8.
HRMS¼252.0134 (C9H8N4OS2 requires 252.0133).
Heghe, H. J. Med. Chem. 1987, 30, 1270–1278; (d) Warshaw, J. A.; Watanabe, K. A.
J. Med. Chem. 1990, 33, 1663–1666; (e) Huang, J.-T.; Chen, L.-C.; Wang, L.; Kim,
M.-H.; Warshaw, J. A.; Armstrong, D.; Zhu, Q.-Y.; Chou, T.-C.; Watanabe, K. A.;
Matulic-Adamic, J.; Su, T.-L.; Fox, J. J.; Polsky, B.; Baron, P. A.; Gold, J. W. M.;
Hardy, W. D.; Zuckerman, E. J. Med. Chem. 1991, 34, 1640–1646; (f) Rama Rao,
A. V.; Gurjar, M. K.; Lalitha, S. V. S. J. Chem. Soc., Chem. Commun. 1994,1255–1256;
(g) Chen, B. C.; Quinlan, S. L.; Stark, D. R.; Reid, J. G.; Audia, W. H.; George, J. G.;
Eisenreich, E.; Brundidge, S. P. H.; Racha, S.; Spector, R. H. Tetrahedron Lett. 1995,
36, 7957–7960; (h) Xi, Z.; Agback, P.; Plavec, J.; Sandstro¨m, A.; Chattopadhyaya, J.
Tetrahedron 1992, 48, 359–370; (i) Chambert, S.; Gautier,-Luneau, I.; Fontecave,
M.; Decout, J. L. J. Org. Chem. 2000, 65, 249–253.
2. Fox, J. J.; Condington, J. F.; Yung, N. C.; Kaplan, L.; Lampen, J. O. J. Am. Chem. Soc.
1958, 80, 5155–5160.
3. Tolstikov, G. A.; Mustafin, A. G.; Gataullin, R. R.; Spirikhin, L. V.; Sultanova, V. S.;
Abdrakhmanov, I. B. Russ. Chem. Bull. 1993, 1137–1141.
4. Mustafin, A. G.; Suyundukova, M. V.; Gataullin, R. R.; Spirikhin, L. V.; Ab-
drakhmanov, I. B.; Tolstikov, G. A. Izv. Akad. Nauk. Ser. Khim 1997, 1420–1421.
5. Hrebabecky, H.; Holy, A. Carbohydr. Res. 1991, 216, 179–186.
6. Robles, R.; Rodrigues, C.; Izquierdo, I.; Plaza, M. T.; Mota, A.; de Cienfuegos, L. A.
Tetrahedron: Asymmetry 2000, 11, 3069–3077.
d
4.5.5. 4-Amino-6-p-nitrostyryl-2,3-dihydro-3-thioxo-1,2,4-triazin-
5(4H)-one 12f
Yellowplates, yield 76%, mp 270–271 ꢁC. MS: m/z¼291 (Mþ, 99%).
IR: 3326, 3085, 3034, 2941, 1674, 1594, 1556, 1514, 1341, 1278, 1246,
739. 1H NMR (DMSO-d6):
d
6.58 (s, 2H, NH2), 7.34 (d, 1H, J 16.4), 7.90
(d,1H, J 16.4), 7.96 (d, 2H, J 8.6), 8.23 (d, 2H, J 8.6),14.25 (s,1H, NH).13
NMR (DMSO-d6): 129.5, 129.8, 133.8, 138.3, 146.4, 148.0, 152.6,
C
d
153.7, 173.1. Anal. Calcd for C11H9N5O3S (291.3): C 45.36; H 3.11; N
24.04; S 11.01. Found: C 45.30; H 3.09; N 24.00; S 11.02.
Acknowledgements
7. (a) Shaw, G.; Warrener, R. N. J. Chem. Soc. 1959, 50–55; (b) Ueda, T.; Shibuya, S.
Chem. Pharm. Bull. 1970, 18, 1076–1078.
8. Fu, Y. L.; Parthasarathy, R.; Bobek, M. J. Carbohydr. Nucleosides Nucleotides 1978,
5, 79–87.
9. El-Etaibi, A.; Makhseed, S.; Al-Awadi, N. A.; Ibrahim, Y. A. Tetrahedron Lett. 2005,
46, 31–35.
The support of Kuwait University received through research
grant no. SC 08/04, the facilities of Analab/SAF (grant nos. GS01/01,
GS02/01, GS03/01), and the financial support for I.A.A.-J. from the
college of graduate studies are gratefully acknowledged.
10. Herrero, M. A.; Kremsner, J. M.; Kappe, C. O. J. Org. Chem. 2008, 73, 36–47.
11. (a) Ibrahim, Y. A. Carbohydrate Lett. 1996, 1, 425–432; (b) Ibrahim, Y. A. Carbo-
hydr. Lett. 1996, 2, 189–195; (c) Mansour, A. K.; Ibrahim, Y. A.; Khalil, N. A. S. M.
Nucleosides Nucleotides 1999, 18, 2265–2283; (d) El-Barbary, A. A.; Sakran, M. A.;
El-Madani, A. M.; Nielsen, C. J. Heterocycl. Chem. 2005, 42, 935–944; (e) Eid, M.
M.; Badawy, M. A.; Ghazala, M. A. H.; Ibrahim, Y. A. J. Heterocycl. Chem. 1983, 20,
1709–1711.
References and notes
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