Regioselective synthesis of C-nucleosides via condensation of 2-hydrazino-thia-diaza-benzo[a]-azulen-4-one

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Regioselective Synthesis of C-
Nucleosides Via Condensation
of 2-Hydrazino-thia-diaza-
benzo[a]-azulen-4-one
A. B. A. El-Gazzar a
a Department of Photochemistry (Heterocycle and
Nucleoside Unit), National Research Center, Dokki,
Giza, Cairo, Egypt
Published online: 01 Feb 2007.
To cite this article: A. B. A. El-Gazzar (2005): Regioselective Synthesis of C-
Nucleosides Via Condensation of 2-Hydrazino-thia-diaza-benzo[a]-azulen-4-one,
Phosphorus, Sulfur, and Silicon and the Related Elements, 180:1, 283-293
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Phosphorus, Sulfur, and Silicon, 180:283–293, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090509108
Regioselective Synthesis of C-Nucleosides Via
Condensation of 2-Hydrazino-thia-diaza-benzo[a]-
azulen-4-one
A. B. A. El-Gazzar
Department of Photochemistry (Heterocycle and Nucleoside Unit),
National Research Center, Dokki, Giza, Cairo, Egypt
Keywords 2-Hydrazino-10-thia-1,3-diaza-benzo[a]azulen-4-one; 1H; 13C.NMR spec-
troscopy; cyclo-condensation; mono-saccharaides
INTRODUCTION
In connection with my program dealing with the discovery of C-
nucleosides1−6 and acyclic-C-nucleosides1,5 as well as the rapid growth
in the literature dealing with their biological activity in the last 50
years, prompted me to become involved in a program to synthesize
some acyclic-C-nucleosides. Depending on whether the above synthe-
sized 2-hydrazino derivative reacts smoothly with aromatic aldehydes
to give the corresponding hydrazone derivatives, experiments are made
to react this hydrazine derivative with some mono-saccharaides. The
produced hydrazones are cyclized to give acyclic-C-nucleosides which
may show biological activities.
The biological,8 bactericidal,9 and medicinal activities10 of pyrimi-
dine and fused pyrimidine derivatives, prompted me to study the re-
activity of the 2-hydrazine-10-thia-1,3-diaza-benzo[a]azulen-4-one (4)
toward the mono-saccharaides to synthesize new C-nucleosides de-
rived from thieno[2,3-d]pyrimidine (3). Thus, seberone reacted with
ethyl cyanoacetate and sulfur metal in presence of absolute ethanol
and diethylamine to give 2-amino-thiophene-3-ethyl ester11 deriva-
tive (1). The latter compound reacts with potassium thiocyanate12
in dioxane/hydrochloric acid (gas) to give the thieno[2,3-d]pyrimidine
derivative (2), which gives 2-methylthio derivative (3) when treated
with one mole of methyliodide in ethanolic sodium hydroxide solution.13
Received March 5, 2004; accepted June 22, 2004.
Dedicated to Professor Ahmed Saleh Aly on the occasion of his 62nd birthday.
Address correspondence to A. B. A. El-Gazzar, Department of Photochemistry, Na-
tional Research Center, Dokki, Giza, Cairo, Egypt. E-mail: elgazzar2000@hotmail.
com
283

284
A. B. A. El-Gazzar
Action of hydrazine hydrate on the 2-methylthio derivative,4 afforded
the starting material 2-hydrazine-3,5,6,7,8,9-hexahydro-10-thia-1,3-
diaza-benzo[a]azulen-4-one (4).
According to El-gazzar and Shisho13,14 synthesis of pyrimi-
dine derivatives the reaction of 2-hydrazino-10-thia-1,3-diaza-
benzo[a]azulen-4-one (4) with some penta mono-saccharides, namely,
D-arabinose and D-xylose in dry dioxane in the presence of catalytic
amounts of piperidine yielded the corresponding hydrazones 5a,b. The
spectral data beside the correct values in elemental analyses support
the open chain nature of the sugar residue in 5a,b. Moreover, the
IR (KBr) spectrum for 5a displayed absorption bands at 3419 cm−1
(broad, OH), 3241 (NH), 1685 (C O). The NMR spectrum of compound
5b, as an example, showed signals at δ 1.61 (m, 4H, 2CH2), 1.83 (m,
2H, CH2), 2.65 (m, 2H, CH2), 3.27 (m, 2H, CH2), 3.51 (m, 4OH, D2O
exchangeable, OH-2ꢀ, OH-5ꢀ), 4.23 (q, 1H, J = 6 Hz, H-4ꢀ), 4.42 (m, 2H,
H-5ꢀꢀ), 4.63 (d, 1H, J = 5 Hz, H-3ꢀ), 5.79 (dd, 1H, J = 7 Hz, H-2ꢀ), 7.39 (d,
1H, J = 4 Hz, H-1ꢀ), and 10.20–10.65 (brs, NH, D2O exchangeable), (Ex-
perimental, Scheme 1). The hydrazone derivatives 5a,b were stirred at
room temperature in acetic anhydride-pyridine (1:1) mixture to afford
the
corresponding
3-(2ꢀ,3ꢀ,4ꢀ,5ꢀ-O-tetraacetyl-glycosyl)-6,7,8,9,10-
pentahydro-cycloheptathieno[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-
one (7a,b) (Scheme 2). The spectral data beside the correct values in
elemental analyses support the structure. Moreover, it is reported in
literature that N-3 nitrogen atom and not N-1 nitrogen atom involved
in the cyclization in pyrimidine ring.7 Also, there is no signal for
the methylene proton of the triazole, which supports the structure
7a–e not 6a–e. The NMR spectrum of compound 5a, as an example,
showed signals at δ 1.59 (m, 4H, 2CH2), 1.78 (m, 2H, CH2), 1.93 (s,
3H, CH3), 2.09 (s, 3H, CH3), 2.13 (s, 3H, CH3), 2.19 (s, 3H, CH3) 2.61
(m, 2H, CH2), 3.21 (m, 2H, CH2), 4.69 (m, 1H, H-3ꢀ), 5.21 (m, 2H,
H-4ꢀ), 5.43 (m, 1H, H-2ꢀ), 5.79 (m, 1H, H-1ꢀ), 10.11 (brs, NH, D2O
exchangeable).
De-protection of the protected acyclic-C-nucleosides 7a,b could be
achieved by treatment with methanolic ammonia solution (25%) at
room temperature for 24 hours. The de-protected acyclic-C-nucleo-
sides, mainly, 3-glycosyl-6,7,8,9,10-pentahydro-cyclohepta-thieno[2,3-
d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (8a,b), were obtained (Scheme
2). The 13C-NMR for 8b, as an example showed six lines at δ 23.5,
25.2, 27.3, 28.2, 30.4, and 31.65 ppm for the sp3 carbon atoms CH2.
It also, showed three signals at δ 61.3, 67.4, and 71.3 ppm for the sp3
carbon atoms of the C-1ꢀ–C-3ꢀ (CH of the sugar moity). The thienopy-
rimidine and triazole carbons at δ 113.1, 128.0, 130.6, 139.1, 147.8,

Regioselective Synthesis of C-Nucleosides
285
SCHEME 1
and 151.6 ppm. And the only carbonyl group of the pyrimidone ring
resonates at δ 159.7 ppm (see experimental).
Likewise, heating under reflux 2-hydrazino (4) with some aldo-
hexoses namely D-glucose, D-galactose, and D-mannose in boiling
dioxane in presence of catalytic amounts of piperidine yielded the

286
A. B. A. El-Gazzar
SCHEME 2
acyclic-C-nucleosides 5c–e. The structure was confirmed by elemental
1
analysis, and spectral data (Scheme 1, Experimental). The H-NMR
spectrum of compound 5a, as an example, showed signals at δ 1.64
(m, 4H, 2CH2), 1.80 (m, 2H, CH2), 2.62 (m, 2H, CH2), 3.24 (m, 2H,
CH2), 3.53 (m, 5OH, D2O exchangeable), 3.68 (m, 1H, H-5ꢀ), 4.27
(m, 2H, H-6ꢀ, H-6ꢀꢀ), 4.42 (m, 1H, H-4ꢀ), 4.63 (m, 1H, H-3ꢀ), 5.54 (m,
1H, H-2ꢀ), 7.43 (m, 1H, H-1ꢀ), and 10.09–10.25 (brs, NH, D2O ex-
changeable). On the other hand, acetylating of compounds 5c–e with
acetic anhydride-pyridine, at room temperature, afforded the pro-
tected penta-O-acetyl derivatives 7c–e. The spectral data beside the

Regioselective Synthesis of C-Nucleosides
287
correct values in elemental analyses support the cyclic C-nucleosides.
Mainly, 3-(1ꢀ,2ꢀ,3ꢀ,4ꢀ,5ꢀ-O-pentaacetyl-glucosyl)–6,7,8,9,10-pentahydro-
cycloheptathieno[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (7c). Its
1H-NMR spectrum showed signals at δ 1.61 (m, 4H, 2CH2), 1.78 (m,
2H, CH2), 1.82 (s, 3H, CH3), 1.93 (s, 3H, CH3), 2.09 (s, 3H, CH3), 2.34
(s, 3H, CH3), 2.48 (s, 3H, CH3), 2.63 (m, 2H, CH2), 3.23 (m, 2H, CH2),
4.68 (m, 1H, H-4ꢀ), 5.27 (d, 1H, J = 10.6 Hz, H-3ꢀ), 5.42 (m, 2H, H2ꢀ,5ꢀ),
5.63 (s, 1H, H-2ꢀ), 5.71 (s, 1H, H-1ꢀ), 8.65 (brs, NH, D2O exchangeable).
Finally, the de-protection of the protected acyclic-C-nucleosides of
7c–e could be achieved when they were stirred in methanolic am-
monia solution at room temperature to give the acyclic-C-nucleosides
8c–e. Mainly, 3-glucosyl-6,7,8,9,10-pentahydro-cyclohepta-thieno[2,3-
d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (8c). Its IR (KBr) for compound
8c, as an example, displayed absorption bands around 3440, 3460 (hy-
droxyl groups) and 3265 (NH) cm−1 and revealed the absence of any
absorption in the carbonyl region except that of the carbonyl pyrimi-
done. Also, its NMR spectrum showed at showed signals at δ 1.63 (m,
4H, 2CH2), 1.79 (m, 2H, CH2), 2.61 (m, 2H, CH2), 3.12 (m, 5H, 5OH,
D2O exchangeable), 3.23 (m, 2H, CH2), 3.38 (m, 1H, H-3ꢀ), 3.67 (m, 2H,
H-5ꢀ, H-5ꢀꢀ), 4.28 (m, 1H, H-2ꢀ), 4.63 (m, 1H, H-1ꢀ), 9.25 (brs, NH, D2O
exchangeable).
CONCLUSION
The prepared nucleosides seem to be interesting for biological activity
studies. Furthermore, the present investigation offers rapid and effec-
tive new procedures for the synthesis of C-nucleosides systems.
EXPERIMENTAL
Melting points are uncorrected; IR spectra (KBr): Pye Unicam SP-1000
cm−1; 1H-nmr/13C-nmr spectra (DMSO-d6), (CDCl3): Varian Gemini 200
MHz Spectrometer, TMS as internal standard, chemical shifts in δ
(ppm). Micro-analytical data were preformed by the Micro-analytical
Center at Cairo University and National Research Centre (Egypt). El-
emental analyses (C, H and N) are in accordance with the calculated
values (Table I).
2-(Glycosyl-hydrazon)-3,5,6,7,8,9-hexahydro-10-thia-
1,3-diaza-benzo[a]azulen-4-one (5a–e)
General procedure. A solution of compounds 4 (10 mmol) and al-
dopentoses or aldohexoses (10 mmol) in dry dioxane in presence of
catalytic amounts of pipridine, The mixture was refluxed for 3–5 h in a
mixture of acetic anhydride-pyridine (20 ml: 20 ml) was stirred at room

288
A. B. A. El-Gazzar
TABLE I Physical Data for the Products 5, 7, 8
Elemental analyses
calcd./found
m.p.
◦C
Yield
%
M.F.
(M. wt.)
Comp. no.
C
H
N
5a
213–215
melted
221–223
melted
189–192
melted
201–203
melted
195–197
melted
207–209
melted
186–188
melted
167–169
melted
179–181
melted
191–193
melted
153–155
melted
161–163
melted
141–143
melted
130–133
melted
147–150
melted
65
63
65
66
68
59
61
53
60
52
51
53
57
55
57
C16H22N4O5S
382.4
50.25
50.31
50.25
50.19
49.50
49.63
49.50
49.45
49.50
49.61
52.55
52.46
52.55
52.43
52.25
52.19
52.25
52.16
52.25
52.20
50.52
50.47
50.52
50.43
49.75
49.67
49.75
49.61
49.75
49.58
5.80
5.74
5.80
5.72
5.87
5.82
5.87
5.68
5.87
5.74
5.14
5.08
5.14
5.11
5.20
5.13
5.20
5.16
5.20
5.10
5.30
5.23
5.30
5.19
5.40
5.26
5.40
5.42
5.40
5.37
14.65
14.38
14.65
14.47
13.58
13.43
13.58
13.39
13.58
13.45
10.21
10.13
10.21
10.09
9.03
5b
5c
5d
5e
7a
7b
7c
7d
7e
8a
8b
8c
8d
8e
C
16H22N4O5S
382.4
C
17H24N4O6S
412.5
C17H24N4O6S
412.5
C
C
C
17H24N4O6S
412.5
24H28N4O9S
548.6
24H28N4O9S
548.6
C
C
27H32N4O11
620.6
27H32N4O11
620.6
S
S
S
8.97
9.03
8.93
9.03
C27H32N4O11
620.6
9.14
C
C
C
C
16H20N4O5S
14.73
14.56
14.73
14.66
13.65
13.53
13.65
13.49
13.65
13.57
380.4
16H20N4O5S
380.4
17H22N4O6S
410.4
17H22N4O6S
410.4
C17H22N4O6S
410.4
temperature for 24 h, poured into water (100 ml), neutralized with hy-
drochloric acid solution. The solid that separated was filtered, washed
with ethanol, dried, and crystallized from the proper solvent to produce
5a–e, in good yields.
2-(Arabinosylhydrazon)-3,5,6,7,8,9-hexahydro-10-thia-
1,3-diaza-benzo[a]azulen-4-one (5a)
From compound 4 (2.50 g, 10 mmol), D-arabinose (1.50 g, 10 mmol).
The compound was obtained as a white powder, crystallized from diox-
ane. IR (KBr) cm−1: 3419 (broad, OH), 3241 (NH), 1685 (C O). 1H-NMR
(DMSO-d6) ppm: δ 1.59 (m, 4H, 2CH2), 1.78 (m, 2H, CH2), 2.63 (m,

Regioselective Synthesis of C-Nucleosides
289
2H, CH2), 3.24 (m, 2H, CH2), 3.37 (m, 4OH, D2O exchangeable, OH-
2ꢀ, OH-5ꢀ), 4.21 (q, 1H, J = 5.8 Hz, H-4ꢀ), 4.39 (m, 2H, H-5ꢀꢀ), 4.59 (d,
1H, J = 5.2 Hz, H-3ꢀ), 5.73 (dd, 1H, J = 6.7 Hz, H-2ꢀ), 7.37 (d, 1H, CH
methylene) and 10.08–10.45 (brs, NH, D2O exchangeable).
2-(Xylosylhydrazon)-3,5,6,7,8,9-hexahydro-10-thia-
1,3-diaza-benzo[a]azulen-4-one (5b)
From compound 4 (2.50 g, 10 mmol), D-xylose (1.50 g, 10 mmol). The
compound was obtained as a white powder, crystallized from dioxane.
1
IR (KBr) cm−1: 3412 (broad, OH), 3219 (NH), 1689 (C O). H-NMR
(DMSO-d6) ppm: δ 1.61 (m, 4H, 2CH2), 1.83 (m, 2H, CH2), 2.65 (m,
2H, CH2), 3.27 (m, 2H, CH2), 3.51 (m, 4OH, D2O exchangeable, OH-
2ꢀ, OH-5ꢀ), 4.23 (q, 1H, J = 6 Hz, H-4ꢀ), 4.42 (m, 2H, H-5ꢀꢀ), 4.63 (d, 1H,
J = 5 Hz, H-3ꢀ), 5.79 (dd, 1H, J = 7 Hz, H-2ꢀ), 7.39 (d, 1H, CH methylene)
and 10.20–10.65 (brs, NH, D2O exchangeable).
2-(Glucosylhydrazon)-3,5,6,7,8,9-hexahydro-10-thia-
1,3-diaza-benzo[a]azulen-4-one (5c)
From compound 4 (2.50, 10 mmol), D-glucose (1.80, 10 mmol). The
compound was obtained as a white powder, crystallized from dioxane.
1
IR (KBr) cm−1: 3429 (broad, OH), 3217 (NH), 1686 (C O). H-NMR
(DMSO-d6) ppm: δ 1.60 (m, 4H, 2CH2), 1.76 (m, 2H, CH2), 2.63 (m, 2H,
CH2), 3.23 (m, 2H, CH2), 3.60 (m, 5H, 5OH, D2O exchangeable OH-2ꢀ-
OH-6ꢀ), 4.25 (m, 1H, CH, H-3ꢀ), 4.35 (m, 2H, CH2, H2–6ꢀ), 4.50 (m, 2H,
2CH, H-3ꢀ and H-4ꢀ), 5.20 (dd, 1H, CH, J = 7.5 Hz, H-2ꢀ), 7.65 (d, 1H,
J = 7.5, H-1ꢀ), 11.30 (brs, 1H, NH, D2O exchangeable) and 11.45 (brs,
1H, NH, D2O exchangeable).
2-(Galactosylhydrazon)-3,5,6,7,8,9-hexahydro-10-thia-
1,3-diaza-benzo[a]azulen-4-one (5d)
From compound 4 (2.50 g, 10 mmol), D-galactose (1.80 g, 10 mmol).
The compound was obtained as a white powder, crystallized from diox-
ane. IR (KBr) cm−1: 3400 (broad, OH), 3249 (NH), 1687 (C O). 1H-NMR
(DMSO-d6) ppm: δ 1.63 (m, 4H, 2CH2), 1.77 (m, 2H, CH2), 2.62 (m, 2H,
CH2), 3.20 (m, 2H, CH2), 3.57 (m, 5H, 5OH, D2O exchangeable OH-2ꢀ-
OH-6ꢀ), 4.23 (m, 1H, CH, H-3ꢀ), 4.31 (m, 2H, CH2, H2–6ꢀ), 4.53 (m, 2H,
2CH, H-3ꢀ and H-4ꢀ), 5.23 (dd, 1H, CH, J = 7.5 Hz, H-2ꢀ), 7.70 (d, 1H,
J = 7.5, H-1ꢀ), 11.21 (brs, 1H, NH, D2O exchangeable) and 11.38 (brs,
1H, NH, D2O exchangeable).
2-(Manosylhydrazon)-3,5,6,7,8,9-hexahydro-10-thia-
1,3-diaza-benzo[a]azulen-4-one (5e)
From compound 4 (2.50 g, 10 mmol), D-mannose (1.80 g, 10 mmol).
The compound was obtained as a white powder, crystallized from

290
A. B. A. El-Gazzar
dioxane. IR (KBr) cm−1: 3406 (broad, OH), 3256 (NH), 1684 (C O). 1H-
NMR (DMSO-d6) ppm: δ 1.64 (m, 4H, 2CH2), 1.79 (m, 2H, CH2), 2.59
(m, 2H, CH2), 3.19 (m, 2H, CH2), 3.49 (m, 5H, 5OH, D2O exchangeable
OH-2ꢀ-OH-6ꢀ), 4.25 (m, 1H, CH, H-3ꢀ), 4.29 (m, 2H, CH2, H2–6ꢀ), 4.50
(m, 2H, 2CH, H-3ꢀ and H-4ꢀ), 5.26 (dd, 1H, CH, J = 7.4 Hz, H-2ꢀ), 7.67
(d, 1H, J = 7.4, H-1ꢀ), 11.23 (brs, 1H, NH, D2O exchangeable) and 11.41
(brs, 1H, NH, D2O exchangeable).
3-(O-Acetylglycosyl)-6,7,8,9,10-pentahydro-cyclohepta-
thieno[2,3-d][1,2,4]-triazolo[4,3-a]pyrimidin-5-one (7a–e)
General procedure. A solution of compounds 5a–e (10 mmol) in a
mixture of acetic anhydridepyridine (20 ml: 20 ml) was stirred at room
temperature for 24 h, poured into water (100 ml). The reaction mix-
ture was then extracted with chloroform several times and after the
removel of chloroform under reduced pressure, the formed crystals was
recrystallized from the proper solvent to produces 7a–e, in good yields.
3-(2ꢀ,3ꢀ,4ꢀ,5ꢀ-O-tetraacetyl-arabinosyl)-6,7,8,9,10-
pentahydro-cyclohepta-thieno[2,3-d][1,2,4]-triazolo-
[4,3-a]pyrimidin-5-one (7a)
From compound 5a (3.82 g, 10 mmol). The compound was obtained
as a white powder, crystallized from ethanol. IR (KBr) cm−1: 3231 (NH),
1756–1734 (4 C O, acetyl) 1687 (C O, pyrimidone). 1H-NMR (CDCl3)
ppm: δ 1.63 (m, 4H, 2CH2), 1.79 (m, 2H, CH2), 1.92 (s, 3H, CH3), 2.15
(s, 3H, CH3), 2.21 (s, 3H, CH3), 2.48 (s, 3H, CH3), 2.61 (m, 2H, CH2),
3.20 (m, 2H, CH2), 4.40 (m, 2H, H2-4ꢀ), 5.20 (m, 1H, H-3ꢀ), 5.45 (m, 1H,
H-2ꢀ), 5.52 (m, 1H, H-1ꢀ), 8.75 (brs, NH, D2O exchangeable).
3-(2ꢀ,3ꢀ,4ꢀ,5ꢀ-O-Tetraacetyl-xylosyl)-6,7,8,9,10-pentahydro-
cyclohepta-thieno[2,3-d]-[1,2,4]-triazolo[4,3-a]pyrimidin-
5-one (7b)
From compound 5b (3.82 g, 10 mmol). The compound was obtained as
a white crystals, crystallized from ethanol. IR (KBr) cm−1: 3220 (NH),
1751–1729 (4 C O, acetyl) 1681 (C O, pyrimidone). 1H-NMR (CDCl3)
ppm: δ 1.61 (m, 4H, 2CH2), 1.76 (m, 2H, CH2), 1.91 (s, 3H, CH3), 2.13
(s, 3H, CH3), 2.20 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.62 (m, 2H, CH2),
3.22 (m, 2H, CH2), 4.41 (m, 2H, H2-4ꢀ), 5.23 (m, 1H, H-3ꢀ), 5.47 (m, 1H,
H-2ꢀ), 5.58 (m, 1H, H-1ꢀ), 8.92 (brs, NH, D2O exchangeable).
3-(1ꢀ,2ꢀ,3ꢀ,4ꢀ,5ꢀ-O-Pentaacetyl-glucosyl)-6,7,8,9,10-
pentahydro-cyclohepta-thieno[2,3-d][1,2,4]-
triazolo[4,3-a]pyrimidin-5-one (7c)
From compound 5c (4.12 g, 10 mmol). The compound was obtained
as a white powder, crystallized from ethanol. IR (KBr) cm−1: 3208 (NH),

Regioselective Synthesis of C-Nucleosides
291
1749–1726 (5 C O, acetyl) 1689 (C O, pyrimidone). 1H-NMR (CDCl3)
ppm: δ 1.61 (m, 4H, 2CH2), 1.78 (m, 2H, CH2), 1.82 (s, 3H, CH3), 1.93
(s, 3H, CH3), 2.09 (s, 3H, CH3), 2.34 (s, 3H, CH3), 2.48 (s, 3H, CH3), 2.63
(m, 2H, CH2), 3.23 (m, 2H, CH2), 4.68 (m, 1H, H-4ꢀ), 5.27 (d, 1H, J =
10.6 Hz, H-3ꢀ), 5.42 (m, 2H, H2ꢀ,5ꢀ), 5.63 (s, 1H, H-2ꢀ), 5.71 (s, 1H, H-1ꢀ),
8.65 (brs, NH, D2O exchangeable).
3-(1ꢀ,2ꢀ,3ꢀ,4ꢀ,5ꢀ-O-Pentaacetyl-Galactosyl)-6,7,8,9,10-
pentahydro-cyclohepta-thieno[2,3,-d][1,2,4]-triazolo
[4,3-a]pyrimidin-5-one (7d)
From compound 5d (4.12 g, 10 mmol). The compound was obtained
as a white powder, crystallized from ethanol. IR (KBr) cm−1: 3225 (NH),
1743–1720 (5 C O, acetyl) 1683 (C O, pyrimidone). 1H-NMR (CDCl3)
ppm: δ 1.58 (m, 4H, 2CH2), 1.76 (m, 2H, CH2), 1.79 (s, 3H, CH3), 1.89
(s, 3H, CH3), 2.07 (s, 3H, CH3), 2.29 (s, 3H, CH3), 2.43 (s, 3H, CH3), 2.60
(m, 2H, CH2), 3.19 (m, 2H, CH2), 4.64 (m, 1H, H-4ꢀ), 5.29 (d, 1H, J =
10.7 Hz, H-3ꢀ), 5.45 (m, 2H, H2ꢀ,5ꢀ), 5.66 (s, 1H, H-2ꢀ), 5.73 (s, 1H, H-1ꢀ),
8.98 (brs, NH, D2O exchangeable).
3-(1ꢀ,2ꢀ,3ꢀ,4ꢀ,5ꢀ-O-Pentaacetyl-manosyl)-6,7,8,9,10-
pentahydro-cyclohepta-thieno[2,3-d][1,2,4]-triazolo
[4,3-a]pyrimidin-5-one (7e)
From compound 5e (4.12 g, 10 mmol). The compound was obtained
as a white powder, crystallized from ethanol. IR (KBr) cm−1: 3218 (NH),
1747–1723 (5 C O, acetyl) 1688 (C O, pyrimidone). 1H-NMR (CDCl3)
ppm: δ 1.62 (m, 4H, 2CH2), 1.73 (m, 2H, CH2), 1.80 (s, 3H, CH3), 1.91 (s,
3H, CH3), 2.11 (s, 3H, CH3), 2.32 (s, 3H, CH3), 2.48 (s, 3H, CH3), 2.61
(m, 2H, CH2), 3.21 (m, 2H, CH2), 4.70 (m, 1H, H-4ꢀ), 5.31 (d, 1H, J =
10.4 Hz, H-3ꢀ), 5.43 (m, 2H, H2ꢀ,5ꢀ), 5.65 (s, 1H, H-2ꢀ), 5.71 (s, 1H, H-1ꢀ),
9.51 (brs, NH, D2O exchangeable).
3-(Glycosyl)-6,7,8,9,10-pentahydro-cycloheptathieno-
[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (8a–e)
General procedure. A solution of compounds 7a–e (10 mmol) in
methanolic ammonia solution (25%, 50 ml), was stirred at room temper-
ature for 24 h, then neutralized with hydrochloric acid solution (under
pH control). The excess of methanol was removed under reduced pres-
sure, whereby a solid was precipitated. The precipitate so-formed was
filtered off, was with cold water dried and recrystallized from the proper
solvent to produces the compounds 8a–e, in good yield.
3-Arabinosyl-6,7,8,9,10-pentahydro-cycloheptathieno-
[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (8a)
From compound 7a (2.74 g, 5 mmol). The compound was obtained as
a white powder, crystallized from ethanol. IR (KBr) cm−1: 3445–3465

292
A. B. A. El-Gazzar
(broads band OH), 3229 (NH), 1684 (C O, pyrimidone). 1H-NMR
(CDCl3) ppm: δ 1.62 (m, 4H, 2CH2), 1.76 (m, 2H, CH2), 2.64 (m, 2H,
CH2), 4.45 (m, 4H, 4OH, D2O exchangeable, OH-1ꢀ, OH-4ꢀ), 4.65 (m,
1H, H-3ꢀ), 4.90 (m, 2H, H2-4ꢀ), 5.10 (m, 1H, H-2ꢀ) and 9.32 (brs, NH,
D2O exchangeable).
3-Xylosy-6,7,8,9,10-Pentahydro-cyclohepta-thieno-
[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (8b)
From compound 7b (2.74 g, 5 mmol). The compound was obtained
as a white powder, crystallized from ethanol. IR (KBr) cm−1: 3436–
3468 (broads band OH), 3203 (NH), 1685 (C O, pyrimidone). 1H-NMR
(CDCl3) ppm: δ 1.63 (m, 4H, 2CH2), 1.75 (m, 2H, CH2), 2.65 (m, 2H,
CH2), 4.43 (m, 4H, 4OH, D2O exchangeable, OH-1ꢀ, OH-4ꢀ), 4.67 (m, 1H,
H-3ꢀ), 4.88 (m, 2H, H2–4ꢀ), 5.12 (m, 1H, H-2ꢀ) and 9.20 (brs, NH, D2O
exchangeable); 13C-NMR (CDCl3) ppm: δ 23.5, 25.2, 27.3, 28.2, 30.4, and
31.65 (6C, 6CH2), 61.3, 67.4 and 71.3 (3C, 3CHOH), 113.1, 128.0, 130.6,
139.1, 147.8, and 151.6 (6C, thienopyrimidine and triazole carbons) and
159.7 (C O, pyrimidone).
3-Glucosyl-6,7,8,9,10-pentahydro-cycloheptathieno-
[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (8c)
From compoud 7c (3.10 g, 5 mmol). The compound was obtained
as a white crystals, crystallized from ethanol. IR (KBr) cm−1: 3440–
3460 (broads band OH), 3265 (NH), 1689 (C O, pyrimidone). 1H-NMR
(CDCl3) ppm: δ 1.63 (m, 4H, 2CH2), 1.79 (m, 2H, CH2), 2.61 (m, 2H,
CH2), 3.12 (m, 5H, 5OH, D2O exchangeable), 3.23 (m, 2H, CH2), 3.38
(m, 1H, H-3ꢀ), 3.67 (m, 2H, H-5ꢀ, H-5ꢀꢀ), 4.28 (m, 1H, H-2ꢀ), 4.63 (m, 1H,
H-1ꢀ), 9.25 (brs, NH, D2O exchangeable).
3-Galactosyl-6,7,8,9,10-pentahydro-cycloheptathieno-
[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (8d)
From compound 7d (3.10 g, 5 mmol). The compound was obtained
as a white powder, crystallized from ethanol. IR (KBr) cm−1: 3435–
3456 (broads band OH), 3260 (NH), 1686 (C O, pyrimidone). 1H-NMR
(CDCl3) ppm: δ 1.58 (m, 4H, 2CH2), 1.74 (m, 2H, CH2), 2.59 (m, 2H,
CH2), 3.11 (m, 5H, 5OH, D2O exchangeable), 3.25 (m, 2H, CH2), 3.40
(m, 1H, H-3ꢀ), 3.71 (m, 2H, H-5ꢀ, H-5ꢀꢀ), 4.31 (m, 1H, H-2ꢀ), 4.62 (m, 1H,
H-1ꢀ), 9.51 (brs, NH, D2O exchangeable).
3-Manosyl-6,7,8,9,10-pentahydro-cycloheptathieno-
[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one (8e)
From compound 7e (3.10 g, 5 mmol). The compound was obtained as
a white powder, crystallized from ethanol. IR (KBr) cm−1: 3429–3456

Regioselective Synthesis of C-Nucleosides
293
(broads band OH), 3239 (NH), 1682 (C O, pyrimidone). 1H-NMR
(CDCl3) ppm: δ 1.60 (m, 4H, 2CH2), 1.77 (m, 2H, CH2), 2.62 (m, 2H,
CH2), 3.13 (m, 5H, 5OH, D2O exchangeable), 3.27 (m, 2H, CH2), 3.42
(m, 1H, H-3ꢀ), 3.76 (m, 2H, H-5ꢀ, H-5ꢀꢀ), 4.31 (m, 1H, H-2ꢀ), 4.67 (m, 1H,
H-1ꢀ), 9.37 (brs, NH, D2O exchangeable).
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