First synthesis of thienopyrazole thioglycosides

Article abstract of DOI:10.1080/07328300802236178

Reported is the first method to prepare a new class of thienopyrazole thioglycosides via a one-pot reaction of the sodium thienopyrazolthiolate salts with 2,3,4,6-tetra-O-acetyl-α-D-gluco-and galactopyranosyl bromides. The sodium thienopyrazolthiolate salts are prepared using pyrazoldithioic acids and their corresponding mono - and dithiolate salts. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/07328300802236178

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First Synthesis of Thienopyrazole
Thioglycosides
Galal H. Elgemeie a , Wafaa A. Zaghary b , Tamer M. Nasr b & Kamelia M.
Amin c
a Faculty of Science, Department of Chemistry , Helwan University , Cairo,
Egypt
b Faculty of Pharmacy, Pharmaceutical Chemistry Department , Helwan
University , Cairo, Egypt
c Faculty of Pharmacy, Pharmaceutical Chemistry Department , Cairo
University , Cairo, Egypt
Published online: 07 Aug 2008.
To cite this article: Galal H. Elgemeie , Wafaa A. Zaghary , Tamer M. Nasr & Kamelia M. Amin (2008) First
Synthesis of Thienopyrazole Thioglycosides, Journal of Carbohydrate Chemistry, 27:6, 345-356
To link to this article: http://dx.doi.org/10.1080/07328300802236178
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Journal of Carbohydrate Chemistry, 27:345–356, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300802236178
First Synthesis of
Thienopyrazole
Thioglycosides
Galal H. Elgemeie,1 Wafaa A. Zaghary,2 Tamer M. Nasr,2
and Kamelia M. Amin3
1Faculty of Science, Department of Chemistry, Helwan University, Cairo, Egypt
2Faculty of Pharmacy, Pharmaceutical Chemistry Department, Helwan University,
Cairo, Egypt
3Faculty of Pharmacy, Pharmaceutical Chemistry Department, Cairo University, Cairo,
Egypt
Reported is the first method to prepare a new class of thienopyrazole thioglycosides via a
one-pot reaction of the sodium thienopyrazolthiolate salts with 2,3,4,6-tetra-O-acetyl-a-
D-gluco- and galactopyranosyl bromides. The sodium thienopyrazolthiolate salts are
prepared using pyrazoldithioic acids and their corresponding mono- and dithiolate salts.
Keywords Thienopyrazole thioglycosides, Sodium thienopyrazolthiolate salts, Pyra-
zoldithioic acids
There is a great interest in the synthesis of nucleosides due to their incorpor-
ation into DNA, RNA, protein, and all intracellular essential nucleotides.
Chemical modification of nucleosides is an important approach to fight
various infections and cancer. In recent reports from our laboratory, we
described the preparation of different novel functionalized pyrimidine and
pyridine thioglycosides, which revealed antagonistic activity against human
carcinoma cells and HIV.[1–3] Earlier, we had reported the use of dihydropyri-
dinethione glycosides as P-glycoprotein (Pgp) substrates or inhibitors
of protein glycosylation.[4] These common features encouraged us to develop
a new straightforward route for the synthesis of these compounds. Here,
we describe the synthesis of thienopyrazole thioglycosides through reaction
of sodium thienopyrazolthiolates with a-halogeno sugars. To our knowledge,
this is the first thienopyrazole thioglycoside ring system to be reported. The
Received March 20, 2008; accepted May 29, 2008.
Address correspondence to Galal H. Elgemeie, Faculty of Science, Department of Chem-
istry, Helwan University, Ain-Helwan, Cairo, Egypt. E-mail: elgemeie@yahoo.com
345

G. H. Elgemeie et al.
346
sequence of reactions followed in the preparation of the compounds is
summarized in Charts 1 through 3. Thus, it has been found that pyrazolin-5-
one 1 reacted with carbon disulfide in the presence of sodium ethoxide to
afford the sodium dithiolate salts 2. Compounds 2 were readily monoalkylated
to give the stable sodium salts of monoalkylthio derivatives. Thus, one equival-
ent of phenacyl bromide or methyl iodide gave the corresponding sodium salts
of monoalkylated products 3 or 4, respectively. When neutralized with hydro-
chloric acid 3 and 4 gave the novel thiol products 8 and 9. Compounds 3 and
4 reacted with 2,3,4,6-tetra-O-acetyl-a-D-gluco- or galactopyranosyl bromides
5a,b in ethanol at rt to give the corresponding S-glycosides 6 and 7 in high
yields. These compounds were also prepared by the reaction of the thiols 8
and 9 with 2,3,4,6-tetra-O-acetyl-a-D-gluco- or galacto-pyranosyl bromides 5
in KOH-acetone at rt for 12 h. The IR spectrum of 6a revealed the presence
of NH band at 3300 cm21, the mass spectrum showed a molecular formula
C27H30N2O11S2 (Mþ ¼ 622), and the 1H NMR spectrum indicated the
anomeric proton as a doublet at d 6.05 ppm with spin-spin coupling constant
of 10.11 Hz, while the other six glucose protons resonated at d 3.95 to
5.50 ppm. The four acetyl groups appeared as four singlets at d 1.95 to
2.00 ppm. Furthermore, the 13C NMR spectrum of 6a represented a signal at
d 80.00 ppm corresponding to the C-10 atom of the b-configuration.
When compounds 2a,b (Chart 2) were subjected to monoalkylation
with 2,3,4,6-tetra-O-acetyl-a-D-gluco- and galactopyranosyl bromides 5 they
yielded compounds 8 that, upon neutralization to ph 7, yielded the glycoside
thiols 10. These compounds could also be prepared by alkylation of the
dithiol derivatives 9 (obtained by neutralization of compound 2) with one equiv-
alent of 5. The structures of compounds 10 were established on the basis of
their elemental analyses, MS, IR, and 1H NMR spectroscopies. The mass
spectrum of 10b was compatible with the molecular formula C19H24N2O10S2
(Mþ ¼ 580). The 1H NMR spectrum indicated the anomeric proton as a
doublet at d ¼ 5.95 ppm with spin-spin coupling constant of 10.11 Hz, while
the other six galactose protons resonated at d ¼ 4.00 to 5.40 ppm. The acetyl
groups appeared as four singlets at d ¼ 1.90 to 2.15 ppm. The synthetic
pathways adopted for the preparation of our target thienopyrazole thioglyco-
sides are illustrated in Chart 3. Compound 3 was cyclized in refluxing
sodium ethoxide to give the corresponding sodium thieno[3,4-c]pyrazole-
thiolate 11 that upon alkylation with halosugars 5 yielded the corresponding
2-(glycopyranosylthio)thienopyrazole derivatives 12. When compound 3 was
cyclized in refluxing sodium ethoxide followed by acidification it afforded the
thienopyrazole-4-thiol 13, which was coupled with halosugars 5 in KOH-
acetone to yield also compounds 12. The structures of the reaction products
12 were established and confirmed on the basis of their elemental analyses
and spectral data (MS, IR, 1HNMR, 13CNMR). Thus, the mass spectrum
of 12a revealed a molecular formula of C27H28N2O10S2 (Mþ ¼ 604). The

Synthesis of Thienopyrazole Thioglycosides
347
Chart 1

G. H. Elgemeie et al.
348
Chart 2
1H NMR spectrum for 12b showed the anomeric proton as a doublet at d
5.90 ppm with a spin-spin coupling constant of 9.8 Hz, while the other six
galactose protons resonated at d 4.05 to 5.40 ppm and the four acetyl groups
appeared as four singlets at d 1.80 to 2.00 ppm.

Synthesis of Thienopyrazole Thioglycosides
349
Chart 3
EXPERIMENTAL
All melting points were uncorrected on a Gallenkamp melting point appar-
atus. The IR spectra were recorded (KBr disk) on a Perkin Elmer 1650 FT-
1
IR instrument. The H NMR spectra were measured on a Varian 400 MHz
spectrometer for solution (CD3)2SO using Si(CH3)4 as an internal standard.
Mass spectra were recorded on a Varian MAT 112 spectrometer. Elemental
analyses were obtained from the Microanalytical Data Center at Cairo Uni-
versity, Egypt.

G. H. Elgemeie et al.
350
Progress of the reactions was monitored by TLC using aluminum sheets
coated with silica gel F254 (Merck). Viewing under a short-wavelength UV
lamp effected detection. All evaporations were carried out under reduced
pressure at 408C.
Sodium 5-methylpyrazol-3-one-4-methylenedithiolates
(2a,b)
General Procedure
A solution of pyrazolones 1a,b (0.01 mol) and sodium ethoxide (0.46 g,
0.02 mol) in absolute ethanol (20 mL) was refluxed for 20 min. The reaction
mixture was cooled to rt; carbon disulphide (0.01 mol) was added. The
reaction mixture was stirred at rt for 30 min, and then the solution was evap-
orated and the formed solid product was collected by filtration.
Sodium 5-methylpyrazol-3-one-4-[(2-oxo-2-
phenylethyl)thio]methyl-enethiolates (3a,b)
General Procedure
A solution of compounds 2a,b (0.01 mol) and phenacyl bromide (1.98 g,
0.01 mol) in ethanol (20 mL) was stirred at rt for 2 h, the solution was evapor-
ated, and the formed solid product was collected and recrystallized from
methanol.
Sodium 5-methylpyrazol-3-one-4-(methylthio)
methylenethiolates (4a,b)
General Procedure
A solution of compounds 2a,b (0.01 mol) and methyl iodide (0.01 mol) in
ethanol (20 mL) was stirred at rt for 2 h, the solution was evaporated, and
the formed solid product was collected by filtration.
(4Z)-4-fmercapto[(2-oxo-2-phenylethyl)thio]methyleneg-5-
methyl-pyrazol-3-ones (8a,b)
General Procedure
A solution of compounds 3a,b in ethanol (20 mL) was poured on cold water
and treated with hydrochloric acid until just acidic and the formed solid
products 8a,b were collected by filtration and recrystallized from ethanol.

Synthesis of Thienopyrazole Thioglycosides
351
4-[Mercapto(methylthio)methylene]-5-methylpyrazol-3-
ones (8a,b)
General Procedure
A solution of compounds 4a,b in ethanol (20 mL) was poured on cold water
and treated with hydrochloric acid until just acidic and the formed solid
products 9a,b were collected by filtration and recrystallized from ethanol.
(4E)-5-methyl-4-f[(2-oxo-2-phenylethyl)thio](20,30,40,60-tetra-
O-acetyl-b-D-gluco or galactopyranosylthio)methyleneg-
2,4-dihydro-3H-pyrazol-3-ones (6a,b)
General Procedure
Method A
To a solution of compound 3a (3.14 g, 0.01 mol) in ethanol (30 mL), a solution
of 2,3,4,6-tetra-O-acetyl-a-D-gluco or galactopyranosyl bromide 5a,b (4.10 g,
0.01 mol) in acetone (20 mL) was added. The reaction mixture was stirred at
rt until completion (TLC, 16 h) and then evaporated under reduced pressure,
and the residue was washed with distilled water to remove the sodium
bromide formed. The resulting product was recrystallized from ethanol.
Method B
A solution of compound 8a (2.92 g, 0.01 mol) in aqueous potassium hydrox-
ide [0.56 g (0.01 mol) in distilled water (6 mL)] was added to a solution of
2,3,4,6-tetra-O-acetyl-a-D-gluco- or galactopyranosyl bromide 5a,b (4.10 g,
0.01 mol) in acetone (30 mL). The reaction mixture was stirred at rt until com-
pletion (TLC, 16 h) and then evaporated under reduced pressure, and the
residue was washed with distilled water to remove the formed potassium
bromide salt. The resulting product was recrystallized from ethanol.
6a: brown, m.p. 2138C (from EtOH), yield (65% method A, 75% method B). IR
1
(KBr) nmax/cm21 3300 (NH), 1750 (CO), 1690 (CO). H NMR (DMSO) d 1.95–
2.00 (4s, 12H, 4 ꢀ CH3CO), 2.40 (s, 3H, CH3), 2.90 (s, 1H, OH), 3.95–4.15
(m, 3H, 60-H2, 50-H), 4.25 (t, 1H, 40-H), 4.90 (s, 2H, CH2), 5.10 (t, 1H, 30-H), 5.50
(t, 1H, 20-H), 6.05 (d, 1H, 10-H), 7.50–8.10 (m, 5H, C6H5). 13C NMR (DMSO)
d 14.93 (Ar-CH3), 20.72–20.87 (4 ꢀ CH3), 42.35 (SCH2), 61.83 (CH2, C-60),
66.42 (C-40), 68.26 (C-20), 71.05 (C-30), 71.52 (C-50), 72.47 (C-10), 129.00–156.00
(aromatic carbons), 160.00 (55C-S), 165.00–185.00 (6 ꢀ CO). C27H30N2O11S2,
Calcd: C, 52.07; H, 4.86; N, 4.50. Found: C, 52.29; H, 4.83; N, 4.85%.
6b: Brown, m.p. 2308C (from EtOH), yield (68% method A, 76% method B).
IR (KBr) nmax/cm21 3200 (NH), 1751 (CO), 1681 (CO). 1H NMR (DMSO)
d 1.90–2.20 (4s, 12H, 4 ꢀ CH3CO), 2.45 (s, 3H, CH3), 4.00–4.10 (m, 3H,

G. H. Elgemeie et al.
352
60-H2, 50-H), 4.45 (t, 1H, 40-H), 4.95 (s, 2H, CH2), 5.25–5.45 (m, 2H, 30-H, 20-H),
6.00 (d, 1H, 10-H), 7.40–8.10 (m, 5H, C6H5). 13C NMR (DMSO) d 14.93 (Ar-
CH3), 20.70–20.87 (4 ꢀ CH3), 42.36 (SCH2), 61.41 (CH2, C-60), 67.65 (C-40),
68.60 (C-20), 70.63 (C-30), 70.81 (C-50), 80.00 (C-10), 128.00–146.00 (aromatic
carbons), 160.15 (55C-S), 165.21–183.00 (6 ꢀ CO). C27H30N2O11S2, Calcd: C,
52.07; H, 4.86; N, 4.50. Found: C, 51.85; H, 5.03; N, 4.51%.
5-Methyl-4-[(methylthio)(20,30,40,60-tetra-O-acetyl-b-D-gluco
or gala-ctopyranosylthio)methylene]-2,4-dihydro-3H-
pyrazol-3-ones (7a,b)
General Procedure
Method A
To a solution of compound 4a (2.10 g, 0.01 mol) in ethanol (30 mL), a solution
of 2,3,4,6-tetra-O-acetyl-a-D-gluco or galactopyranosyl bromide 5a,b (4.10 g,
0.01 mol) in acetone (20 mL) was added. The reaction mixture was stirred at
rt until completion (TLC, 13 h) and then evaporated under reduced pressure,
and the residue was washed with distilled water to remove the sodium
bromide formed. The resulting product was recrystallized from ethanol.
Method B
A solution of compounds 9a (1.88 g, 0.01 mol) in aqueous potassium
hydroxide [0.56 g (0.01 mol) in distilled water (6 mL)] was added to a solution
of 2,3,4,6-tetra-O-acetyl-a-D-gluco- or galactopyranosyl bromide 5a,b (4.10 g,
0.01 mol) in acetone (30 mL). The reaction mixture was stirred at rt until com-
pletion (TLC, 13 h) and then evaporated under reduced pressure, and the
residue was washed with distilled water to remove the formed potassium
bromide. The resulting product was recrystallized from ethanol.
7a: yellow, m.p. 1928C (from EtOH), yield (70% method A, 78% method B). IR
(KBr) nmax/cm21 3371 (NH), 1751 (CO). 1H NMR (DMSO) d 1.90–2.10 (4s, 12H,
4 ꢀ CH3CO), 2.45 (s, 1H, OH), 2.60 (s, 3H, CH3), 2.65 (s, 3H, SCH3), 3.90–4.05
(m, 3H, 60-H2, 50-H), 4.20 (t, 1H, 40-H), 5.05 (t, 1H, 30-H), 5.45 (t, 1H, 20-H), 6.00
(d, 1H, 10-H). 13C NMR (DMSO) d 13.92 (Ar-CH3), 15.66 (S-CH3), 18.83–20.84
(4 ꢀ CH3), 59.91 (CH2, C-60), 68.48 (C-40), 71.10 (C-20), 71.48 (C-30), 73.01 (C-50),
74.53 (C-10), 113.00 (C-4), 143.74 (C-5), 144.68 (C-3 enol form), 160.15 (55C-S),
169.21–169.52 (4 ꢀ CO). C20H26N2O10S2, Calcd: C, 46.31; H, 5.06; N, 5.40.
Found: C, 46.70; H, 5.14; N, 5.42%.
7b: Yellow, m.p. 1458C (from EtOH), yield (69% method A, 77% method B). IR
(KBr) nmax/cm21 3340 (NH), 1751 (CO). 1H NMR (DMSO) d 1.90–2.15 (4s, 12H,
4 ꢀ CH3CO), 2.45 (s, 1H, OH), 2.60 (s, 3H, CH3), 2.65 (s, 3H, SCH3), 4.05–4.15
(m, 3H, 60-H2, 50-H), 4.45 (t, 1H, 40-H), 5.30–5.45 (m, 2H, 30 - H -20-H), 5.90
(d, 1H, 10-H). 13C NMR (DMSO) d 14.52 (Ar-CH3), 18.05 (S-CH3), 18.87–

Synthesis of Thienopyrazole Thioglycosides
353
20.85 (4 ꢀ CH3), 61.39 (CH2, C-60), 64.89 (C-40), 67.42 (C-20), 68.87 (C-30), 70.97
(C-50), 71.08 (C-10), 113.81 (C-4), 144.63 (C-5), 160.00 (55C-S), 165.00 (NHCO),
169.24–170.32 (4 ꢀ CO). C20H26N2O10S2, Calcd: C, 46.31; H, 5.06; N, 5.40.
Found: C, 46.38; H, 5.31; N, 5.85%.
Sodium 5-methyl-3-one-pyrazole-4-(20,30,40,60-tetra-O-acetyl-
b-D-gluco or galactopyranosylthio)methylenethiolates
(8a–d)
General Procedure
To a solution of compounds 2a,b (0.01 mol) in ethanol (30 mL), a solution of
2,3,4,6-tetra-O-acetyl-a-D-gluco or galactopyranosyl bromide 5a,b (4.10 g,
0.01 mol) in acetone (20 mL) was added. The reaction mixture was stirred at
rt until completion (TLC, 12 h) and then evaporated under reduced pressure,
and the product was separated by filtration.
8a: yellow, m.p. .3008C (from EtOH), yield (74%). IR (KBr) nmax/cm21
3417 (NH), 1751 (CO), 1596 (C55C). C19H23N2O10S2Na.
8b: yellow, m.p. .3008C (from EtOH), yield (73%). IR (KBr) nmax/cm21
3417 (NH), 1743 (CO), 1596 (C55C). C19H23N2O10S2Na.
8c: yellow, m.p. .3008C (from EtOH), yield (82%). IR (KBr) nmax/cm21
1751 (CO), 1612 (C55C). C25H27N2O10S2Na.
8d: yellow, m.p. .3008C (from EtOH), yield (81%). IR (KBr) nmax/cm21
1743 (CO), 1620 (C55C). C25H27N2O10S2Na.
4-(Dimercaptomethylene)-5-methyl-pyrazol-3-ones (9a,b)
General Procedure
A solution of compound 2a,b in ethanol(20 mL) was poured on cold water
and treated with hydrochloric acid until just acidic and the formed solid
product 9a,b was collected by filtration and recrystallized from ethanol.
4-[Mercapto(20,30,40,60-tetra-O-acetyl-b-D-gluco or
galactopyrano-sylthio)methylene]-5-methyl-pyrazol-3-
ones (10a–d)
General procedures
Method A
A solution of compounds 8a–d (0.01 mol) in ethanol (30 mL) was poured on
ice-cooled water and the medium was adjusted to pH 7 using dilute acetic acid,

G. H. Elgemeie et al.
354
and the formed solid product 10a–d was collected by filtration and recrystal-
lized from ethanol.
Method B
A solution of compounds 9a,b (0.01 mol) in aqueous potassium hydroxide
[0.56 g (0.01 mol) in distilled water (6 mL)] was added to a solution of 2,3,4,6-
tetra-O-acetyl-a-D-gluco- or galactopyranosyl bromide 5a,b (4.10 g, 0.01 mol)
in acetone (30 mL). The reaction mixture was stirred at rt until completion
(TLC, 15 h) and then evaporated under reduced pressure, and the residue
was washed with distilled water to remove the formed potassium bromide.
The resulting product was recrystallized from ethanol.
10a: yellow, m.p. 1108C (from EtOH), yield (70% method A, 77% method B). IR
1
(KBr) nmax/cm21 3200 (NH), 2507 (SH), 1751 (CO). H NMR (DMSO) d 1.95–
2.00 (4s, 12H, 4 ꢀ CH3CO), 2.45 (s, 3H, CH3), 4.00–4.20 (m, 3H, 60-H2, 50-H),
4.95 (t, 1H, 40-H), 5.20 (t, 1H, 30-H), 5.40 (t, 1H, 20-H), 5.95 (d, 1H, 10-H). 13C
NMR (DMSO) d 15.92 (Ar-CH3), 20.65–20.87 (4 ꢀ CH3), 61.97 (CH2, C-60),
68.37 (C-40), 68.81 (C-20), 73.92 (C-30), 75.25 (C-50), 81.91 (C-10), 116.00 (C-4),
147.00 (C-5), 160.10 (C-S), 165.00 (NHCO), 169.45–170.29 (4 ꢀ CO).
C19H24N2O10S2, Calcd: C, 45.22; H, 4.80; N, 5.55. Found: C, 45.00; H, 4.76; N,
5.35%.
10b: Yellow, m.p. 1558C (from EtOH), yield (73% method A, 80% method B). IR
1
(KBr) nmax/cm21 3209 (NH), 2550 (SH), 1751 (CO). H NMR (DMSO) d 1.90–
2.15 (4s, 12H, 4 ꢀ CH3CO), 2.45 (s, 3H, CH3), 4.00–4.10 (m, 3H, 60-H2, 50-H),
4.30 (t, 1H, 40-H), 5.30–5.40 (m, 2H, 30-H, 20-H), 5.95 (d, 1H, 10-H). 13C NMR
(DMSO) d 15.91 (Ar-CH3), 20.69–20.89 (4 ꢀ CH3), 61.94 (CH2, C-60), 66.22
(C-40), 68.01 (C-20), 71.73 (C-30), 74.33 (C-50), 82.28 (C-10), 115.00 (C-4), 145.00
(C-5),
160.15
(C-S),
165.00
(NHCO),
169.66–170.33
(4 ꢀ CO).
C19H24N2O10S2, Calcd: C, 45.22; H, 4.80; N, 5.55. Found: C, 45.21; H, 4.59;
N, 5.51%.
10c: Yellow, m.p. 1658C (from EtOH), yield (82% method A, 88% method B). IR
(KBr) nmax/cm21 3020 (CH, aromatic), 2939 (CH, aliphatic), 2507 (SH), 1751
1
(CO). H NMR (DMSO) d 1.90–2.00 (4s, 12H, 4 ꢀ CH3CO), 2.55 (s, 3H, CH3),
4.00 (s, 2H, 60-H), 4.15 (m, 1H, 50-H), 4.95 (t, 1H, 40-H), 5.20 (t, 1H, 30-H),
5.35 (t, 1H, 20-H), 6.10 (d, 1H, 10-H), 7.20–7.80 (m, 5H, C6H5). 13C NMR
(DMSO) d 18.21 (Ar-CH3), 20.67–20.89 (4 ꢀCH3), 62.04 (CH2, C-60), 68.49
(C-40), 68.92 (C-20), 74.27 (C-30), 75.14 (C-50), 81.30 (C-10), 120.12–150.00
(aromatic and heteroaromatic carbons), 159.00 (C-S), 162.00 (NHCO),
169.38–169.65 (4 ꢀ CO). C25H28N2O10S2, Calcd: C, 51.70; H, 4.82; N, 4.87.
Found: C, 51.99; H, 5.26; N, 4.47%.
10d: Yellow, m.p. 1088C (from EtOH), yield (81% method A, 87% method B). IR
(KBr) nmax/cm21 3020 (CH, aromatic), 2962 (CH, aliphatic), 2507 (SH), 1751
1
(CO). H NMR (DMSO) d 1.90–2.10 (4s, 12H, 4 ꢀ CH3CO), 2.60 (s, 3H, CH3),

Synthesis of Thienopyrazole Thioglycosides
355
4.00 (s, 2H, 60-H), 4.30 (m, 1H, 50-H), 5.00 (t, 1H, 40-H), 5.35 (m, 2H, 30-H, 20-H),
6.05 (d, 1H, 10-H), 7.20–7.80 (m, 5H, C6H5). C25H28N2O10S2, Calcd: C, 51.70; H,
4.82; N, 4.87. Found: C, 51.08; H, 5.46; N, 4.85%.
Sodium 3-methyl-1H-thieno[3,4-c]pyrazol-6-yl-
(phenyl)methanone-4-thiolate (11)
General Procedure
A solution of compound 3 (0.01 mol) and sodium ethoxide (0.01 mol) in
ethanol (20 mL) was refluxed for 3 h, the solution was evaporated, and the
formed solid product was collected by filtration.
(4-Mercapto-3-methyl-1H-thieno[3,4-c]pyrazol-6-yl)
(phenyl)methan-one (13)
General Procedure
A solution of compound 3 in (20 mL) ethanol was poured on cooled water
acidified with hydrochloric acid, and the formed solid product 13 was collected
by filtration and recrystallized from ethanol.
[3-Methyl-4-(20,30,40,60-tetra-O-acetyl-b-D-gluco- and
galacto-pyranosyl-thio)-1H-thieno[3,4-c]pyrazol-6-yl]
(phenyl)methanones (12a,b)
General Procedures
Method A
To a solution of compound 1 (0.01 mol) in ethanol (30 mL), a solution of
2,3,4,6-tetra-O-acetyl-a-D-gluco or galactopyranosyl bromide 5a,b (4.10 g,
0.01 mol) in acetone 20 mL was added. The reaction mixture was stirred at rt
until completion (TLC, 14 h) and then evaporated under reduced pressure,
and the residue was washed with distilled water to remove the sodium
bromide formed. The resulting product was recrystallized from ethanol.
Method B
A solution of compounds 13 (0.01 mol) in aqueous potassium hydroxide
[0.56 g (0.01 mol) in distilled water (6 mL)] was added to a solution of 2,3,4,6-
tetra-O-acetyl-a-D-gluco- or galactopyranosyl bromide 5a,b (4.10 g, 0.01 mol)
in acetone (30 mL). The reaction mixture was stirred at rt until completion
(TLC, 14 h) and then evaporated under reduced pressure, and the residue
was washed with distilled water to remove the formed potassium bromide.
The resulting product was crystallized from ethanol.

G. H. Elgemeie et al.
356
12a: brown, m.p. 1608C (from EtOH), yield (75% method A, 80% method B). IR
(KBr) nmax/cm21 3201 (NH), 1751 (CO). 1H NMR (DMSO) d 1.90–2.00 (4s, 12H,
4 ꢀ CH3CO), 2.10 (s, 3H, CH3), 3.90 (m, 3H, 60-H2, 50-H), 4.20 (t, 1H, 40-H), 4.95
(t, 1H, 30-H), 5.50 (t, 1H, 20-H), 5.90 (d, 1H, 10-H), 7.10–8.10 (m, 5H, C5H4).
C27H28N2O10S2, Calcd: C, 53.62; H, 4.67; N, 4.63. Found: C, 53.12; H, 4.84;
N, 4.95%.
12b: Brown, m.p. 2058C (from EtOH), yield (77% method A, 85% method B). IR
(KBr) nmax/cm21 3193 (NH), 1751 (CO). 1H NMR (DMSO) d 1.80–2.00 (4s, 12H,
4 ꢀ CH3CO), 2.10 (s, 3H, CH3), 4.05 (s, 2H, 60-H), 4.60 (m, 1H, 50-H), 4.95 (t, 1H,
40-H), 5.20–5.40 (m, 2H, 30-H, 20-H), 5.95 (d, 1H, 10-H), 7.00–8.10 (m, 5H, C6H5).
C27H28N2O10S2, Calcd: C, 53.62; H, 4.67; N, 4.63. Found: C, 53.57; H, 4.22; N,
4.70%.
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