A direct route to a new class of acrylamide thioglycosides

Article abstract of DOI:10.1080/07328300802262786

The preparation of a new class of acrylamide thioglycosides via one-pot reaction of the potassium 2-cyanoethylene-1-thiolate salts with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides has been studied. The E-configuration of these thioglycosides was proven by their transformations to the corresponding 5-aminopyrazoles. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/07328300802262786

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A Direct Route to a New Class of Acrylamide
Thioglycosides
Galal H. Elgemeie a , Wafaa A. Zaghary b , Kamelia M. Amin c & Tamer M.
Nasr b
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 , Kamelia M. Amin & Tamer M. Nasr (2008) A Direct
Route to a New Class of Acrylamide Thioglycosides, Journal of Carbohydrate Chemistry, 27:6, 373-378, DOI:
10.1080/07328300802262786
To link to this article: http://dx.doi.org/10.1080/07328300802262786
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Journal of Carbohydrate Chemistry, 27:373–378, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300802262786
A Direct Route to a New
Class of Acrylamide
Thioglycosides
Galal H. Elgemeie,1 Wafaa A. Zaghary,2 Kamelia M. Amin,3
and Tamer M. Nasr2
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
The preparation of a new class of acrylamide thioglycosides via one-pot reaction of the
potassium 2-cyanoethylene-1-thiolate salts with 2,3,4,6-tetra-O-acetyl-a-D-gluco- and
galactopyranosyl bromides has been studied. The E-configuration of these thioglyco-
sides was proven by their transformations to the corresponding 5-aminopyrazoles.
Keywords Acrylamide thioglycosides, Potassium 2-cyanoethylene-1-thiolate salts,
5-Aminopyrazoles
Nucleoside analogs have occupied a significant position in the search for effective
antiviral agents, owing to the fact that a large number of unnatural nucleoside
derivatives have been shown to inhibit infection caused by viruses.[1] Hetero-
cyclic thioglycosides constitute a class of analogs with potential biological
activity.[2] As part of our program directed toward the development of new,
simple, and efficient procedures for the synthesis of antimetabolites[3,4] we
described that pyridine thioglycosides exerted inhibitory effects on both DNA
and RNA containing viruses.[5] Based on these findings, it was of interest to
prepare modified cyclic and acyclic thioglycosides to search for more effective
agents. Here we report novel syntheses of acrylamide thioglycoside derivatives.
The potassium 2-cyanoethylene-1-thiolate salts 3a–d were chosen as the key
Received August 1, 2007; accepted June 9, 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
373

G. H. Elgemeie et al.
374
intermediate. The reaction sequence to prepare the compounds is summarized in
Scheme 1. Substituted acetanilide derivatives 1a–d reacted with phenyl isothio-
cyanate in KOH-EtOH with heating to give the corresponding stable potassium
2-cyano-ethylene-1-thiolate salts 3a–d. The latter react with 2,3,4,6-tetra-
O-acetyl-a-D-gluco- and galacto-pyranosyl bromides 4 in ethanol at rt to give
the corresponding S-glucosides 6a–d or S-galactosides 6e–h, in high yield.
Attempted removal of protecting groups in 6a–h by methanolic ammonia did
not result in formation of the corresponding free glycosides. We suggested that
6a–h should be present in the E and not in the Z form. This was shown by
reacting 6a–h with hydrazine in refluxing ethanol to give the corresponding
Scheme 1

Direct Route to New Class of Acrylamide Thioglycosides
375
5-aminopyrazole derivatives 8a–d. Alternatively, 8a–d could be prepared by
reaction of the 3-methylthiopyrazoles 7a–d with aniline. Compounds 7a–d
were prepared by the reaction of substituted acetanilide derivatives 1 with
carbon disulfide in the presence of sodium ethoxide followed by the alkylation
with methyl iodide to give the ketene S,S-acetals 5; the latter reacts with hydra-
zine to give compounds 7a–d.[6]
In summary, we have achieved the synthesis of acrylamide thioglycosides
by the reaction of the potassium 2-cyanoethylene-1-thiolate salts with
a-glycosyl halides. These acyclic glycosides can be utilized as starting materials
for the synthesis of other carbohydrate derivatives.
EXPERIMENTAL
All melting points were uncorrected on a Gallenkamp melting point apparatus.
The IR spectra were recorded (KBr disk) on a Perkin Elmer 1650 FT-IR instru-
ment. The 1H NMR spectra were recorded on a Varian 400 MHz spectrometer in
(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 University, Egypt.
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.
Compounds 5 and 7 were prepared following reported procedures.[6]
(2e)-3-Anilino-N-Aryl-2-Cyano-3-(20,30,40,60-Tetra-O-Acetyl-b-D-
Gluco- and Galactopyranosylthio)acrylamides (6a–h)
General Procedure
A mixture of N-substituted cyanoacetamide derivatives 1a–d (0.01 mol)
and phenyl isothiocyanate (0.01 mol) was heated for 10 to 20 min in ethanol
(25 mL) containing potassium hydroxide (0.01 mol). After cooling, a solution
of 2,3,4,6-tetra-O-acetyl-(-D-gluco- or galacto-pyranosyl bromide 4a,b
(0.01 mol) in ethanol (20 mL) was added. The reaction mixture was stirred at
rt until completion (TLC) and then evaporated under reduced pressure, and
the residue was washed with distilled water to remove the formed potassium
bromide. The resulting solid product was dried and crystallized from a
mixture of EtOH/DMF.
6a: White, m.p. 1988C (from EtOH/DMF), yield (87%). IR (KBr) nmax/cm21
1
3340 (NH), 2206 (CN), 1751 (CO). H NMR (DMSO) d 1.94–2.02 (4s, 12H,
4 ꢀ CH3CO), 3.66 (m, 2H, H2-60), 4.08 (m, 1H, H-50), 4.84 (m, 2H, H-40, H-30),

G. H. Elgemeie et al.
376
5.20 (d, J1 -2 9.62 Hz, 1H, H-10), 5.25 (t, 1H, H-20), 7.22–7.50 (m, 9H, C6H5,
C6H4), 9.88 (s, 1H, NH). 13C NMR (DMSO) d 20.13–20.37 (4 ꢀ CH3), 61.34
(CH2, C-60), 67.38 (C-40), 69.65 (C-20), 72.62 (C-30), 74.54 (C-50), 83.84 (C-10),
117.85 (CN), 121.17–138.44 (2C6H5), 154.00 (C-2), 160.18 (C-3), 163.70 (C-1),
169.00–169.80 (4 ꢀ CO). C30H31N3O10S, Calcd: C, 57.58; H, 5.00; N, 6.71,
Found: C, 57.24; H, 5.25; N, 6.37%.
0
0
6b: White, m.p. 2058C (from EtOH/DMF), yield (86%). IR (KBr) nmax/cm21
3402 (NH), 2198 (CN), 1743 (CO). 1H NMR (DMSO) (1.90–2.00 (4s, 12H,
4 ꢀ CH3CO), 2.25 (s, 3H, CH3), 3.65 (m, 2H, H2-60), 4.00 (m, 1H, H-50), 4.85
(m, 2H, H-40, H-30), 5.15 (m, 1H, H-20) 5.25 (d, J1 -2 9.9, 1H, H-10), 7.10–7.50
(m, 9H, C6H5, C6H4), 9.55 (s, 1H, NH).13C NMR (DMSO) (20.13–20.37
(5 ꢀ CH3), 61.34 (CH2, C-60), 67.38 (C-40), 69.60 (C-20), 72.62 (C-30), 74.52
(C50), 83.47 (C-20), 83.87 (C-10), 117.85 (CN), 121.24–138.42 (C6H4 and C6H5),
160.04 (C-3), 163.63(C-1), 169.00–169.79 (4 ꢀ CO). C31H33N3O10S, Calcd: C,
58.19; H, 5.20; N, 6.56, Found: C, 58.10; H, 5.35; N, 6.55%.
0
0
6c: White, m.p. 2158C (from EtOH/DMF), yield (77%). IR (KBr) nmax/cm21
1
3402 (NH), 2206 (CN), 1743 (CO). H NMR (DMSO) d 1.90–2.00 (4s, 12H,
4 ꢀ CH3CO), 3.70 (m, 2H, 60-H2), 3.75 (s, 3H, OCH3), 4.00 (m, 1H, H-50), 4.85
(m, 2H, H-40, H-30), 5.15 (d, J1 -2 9.75, 1H, H-10), 5.25 (t, 1H, H-20), 6.80–7.50
(m, 9H, C6H5, C6H4), 9.50 (s, 1H, NH). 13C NMR (DMSO) (20.14–20.37
(4 ꢀ CH3), 55.07 (OCH3), 61.35 (CH2, C-60), 67.40 (C-40), 69.67 (C-20), 72.63
(C-30), 74.51 (C-50), 83.90 (C-10), 113.51 (CN), 117.85–138.41 (C6H4 and
C6H5), 155.88(C-2), 159.94(C-3), 163.64(C-1), 169.01–169.80 (4 ꢀ CO).
C31H33N3O11S, Calcd: C, 56.77; H, 5.08; N, 6.40, Found: C, 57.04; H, 5.20; N,
6.35%.
0
0
6d: White, m.p. 2158C (from EtOH/DMF), yield (77%). IR (KBr) nmax/cm21
1
3402 (NH), 2198 (CN), 1743 (CO). H NMR (DMSO) d 1.90–2.05 (4s, 12H,
4 ꢀ CH3CO), 3.70 (m, 2H, H2-60), 4.00 (m, 1H, H-50), 4.90 (m, 2H, H-40, H-30),
5.20 (d, J1 -2 9.80, 1H, H-10), 5.25 (t, 1H, H-20), 7.20–7.55 (m, 9H, C6H5,
C6H4), 9.80 (s, 1H, NH). 13C NMR (DMSO) d 20.13–20.37 (4 ꢀ CH3), 61.34
(CH2, C-60), 67.37 (C-40), 69.63 (C-20), 72.59 (C-30), 74.56 (C-50), 83.75 (C-10),
117.78 (CN), 122.60–138.47 (C6H4 and C6H5), 160.31 (C-2), 163.58 (C-3),
168.99 (C-1), 169.35–169.79 (4 ꢀ CO). C30H30ClN3O10S, Calcd: C, 54.54; H,
4.54; N, 6.36, Found: C, 54.44; H, 4.80; N, 6.34%.
0
0
6e: White, m.p. 1798C (from EtOH/DMF), yield (85%). IR (KBr) nmax/cm21
1
3397 (NH), 2201 (CN), 1745 (CO). H NMR (DMSO) d 1.85–2.00 (4s, 12H,
4 ꢀ CH3CO), 3.85 (m, 2H, H2-60), 4.10 (m, 1H, H-50), 5.00 (t, 1H, H-40), 5.10
(m, 2H, H-30, 20-H), 5.25 (d, J1 -2 9.8, 1H, H-10), 7.05–7.70 (m, 10H, 2C6H5),
9.60 (s, 1H, NH). 13C NMR (DMSO) d 20.01–20.40 (4 ꢀ CH3), 60.83 (CH2,
C-60), 66.77 (C-40), 67.06 (C-20), 70.64 (C-30), 73. 81 (C-50), 84.03 (C-10), 118.03
(CN), 120.98–138.75 (2C6H5), 155.70 (C-2), 159.61 (C-3), 163.10 (C-1),
0
0

Direct Route to New Class of Acrylamide Thioglycosides
377
169.24–169.70 (4 ꢀ CO). C30H31N3O10S, Calcd: C, 57.58; H, 5.00; N, 6.71,
Found: C, 57.53; H, 5.00; N, 7.06%.
6f: White, m.p. 2108C (from EtOH/DMF), yield (86%). IR (KBr) nmax/cm21
1
3402 (NH), 2198 (CN), 1743 (CO). H NMR (DMSO) d 1.85–2.05 (4s, 12H,
4 ꢀ CH3CO), 2.25 (s, 3H, CH3), 3.85 (m, 2H, H2-60), 4.10 (m, 1H, H-50),
5.00 (t, 1H, H-40), 5.10 (m, 3H, H-30, H-20) 5.30 (d, J1 -2 9.6, 1H, H-10),
7.10–7.50 (m, 9H, C6H5, C6H4), 9.55 (s, 1H, NH). 13C NMR (DMSO) d
20.04–20.47 (5 ꢀ CH3), 60.82 (CH2, C-60), 66.80 (C-40), 67.06 (C-20), 70.65
(C-30), 73.78 (C-50), 84.11 (C-10), 118.03 (CN), 119.66–138.71 (C6H4 and
C6H5), 155.60 (C-2), 159.51 (C-3), 163.09 (C-1), 169.24–169.72 (4 ꢀ CO).
C31H33N3O10S, Calcd: C, 58.19; H, 5.20; N, 6.56, Found: C, 57.90; H, 4.90;
N, 6.64%.
0
0
6g: White, m.p. 1918C (from EtOH/DMF), yield (76%). IR (KBr) nmax/cm21 3409
(NH), 2198 (CN), 1743 (CO). 1H NMR (DMSO) d 1.85–2.05 (4s, 12H, 4 ꢀ CH3CO),
2.25 (s, 3H, CH3), 3.85 (m, 2H, H2-60), 4.10 (m, 1H, H-50), 5.00 (t, 1H, H-40), 5.10
(m, 3H, H-30, H-20), 5.30 (d, J1 -2 9.88, 1H, H-10), 7.10–7.50 (m, 9H, C6H5,
C6H4), 9.55 (s, 1H, NH). 13C NMR (DMSO) d 20.05–20.40 (4 ꢀ CH3), 55.06
(OCH3), 60.80 (CH2, C-60), 66.81 (C-40), 67.05 (C-20), 70.66 (C-30), 73.76 (C-50),
84.14 (C-10), 113.73 (CN), 118.02–138.69 (C6H4 and C6H5), 155.81 (C-2), 159.40
(C-3), 163.10 (C-1), 169.25–169.73 (4 ꢀ CO). C31H33N3O11S, Calcd: C, 56.77; H,
5.08; N, 6.40, Found: C, 57.07; H, 5.20; N, 6.40%.
0
0
6h: White, m.p. 1978C (from EtOH/DMF), yield (87%). IR (KBr) nmax/cm21
1
3394 (NH), 2198 (CN), 1743 (CO). H NMR (DMSO) d 1.90–2.05 (4s, 12H,
4 ꢀ CH3CO), 3.85 (m, 2H, H2-60), 4.10 (m, 1H, H-50), 5.05 (t, 1H, H-40), 5.10
(m, 3H, H-30, H-20), 5.25 (d, J1 -2 9.77, 1H, H-10), 7.10–7.70 (m, 9H, C6H5,
C6H4), 9.75 (s, 1H, NH), 11.00 (s, 1H, CONH). 13C NMR (DMSO) d 19.95–
20.40 (4 ꢀ CH3), 60.90 (CH2, C-60), 66.73 (C-40), 67.09 (C-20), 70.64 (C-30),
73.88 (C-50), 83.90 (C-10), 117.98 (CN), 122.34–138.82 (C6H4 and C6H5),
155.70 (C-2), 159.74 (C-3), 162.92 (C-1), 169.25–169.69 (4 ꢀ CO).
C30H30ClN3O10S, Calcd: C, 54.59; H, 4.54; N, 6.36, Found: C, 54.70; H, 4.40;
N, 6.65%.
0
0
5-Amino-3-(Methylthio)-1H-Pyrazole-4-Carboxanilides
(7a-D)[6]
General Procedure
A mixture of compounds 5a–d (0.01 mol) and hydrazine (0.01 mol) in
ethanol (30 mL) was heated at reflux for 2 h. After cooling, the reaction
mixture was diluted with cooled water and the resulting solid product was
filtered off and recrystallized from ethanol.

G. H. Elgemeie et al.
378
5-Amino-3-Anilino-1H-Pyrazole-4-Carboxanilides (8a–D)
General Procedures
Method (a)
A mixture of compounds 6a–d (0.01 mol) and hydrazine (0.01 mol) in
ethanol (30 mL) was heated at reflux for 2 h. The resulting solid product was
collected by filtration and recrystallized from ethanol.
Method (b)[7]
A mixture of compounds 7a–d (0.01 mol) and aniline (0.01 mol) was heated
for 2 to 3 h at 2008C in an oil bath. The reaction mixture was dissolved in
ethanol and the resulting solid product was filtered off and recrystallized
from ethanol.
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