Synthesis of 1-(2-naphthylsulfonyl)pyrazole-C-glycosides

Article abstract of DOI:10.1081/NCN-120014819

2-Naphthylsulfonylhydrazine was reacted with aromatic aldehydes or aldehydo sugars to give the corresponding hydrazones which undergo Michael addition reactions with malononitrile or ethyl cyanoacetate to form pyrazole derivatives.

Full text of DOI:10.1081/NCN-120014819

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SYNTHESIS OF 1-(2-NAPHTHYLSULFONYL)PYRAZOLE-C-
GLYCOSIDES
Abd El-Hamid Ismail a , Abdel Aleem Hassan Abdel Aleem a , Hamed Abdel Bary a & Samy El-
Assaly a
a Chemistry Department, Menoufia University, Shebin El-Koom, Egypt
Published online: 31 Aug 2006.
To cite this article: Abd El-Hamid Ismail , Abdel Aleem Hassan Abdel Aleem , Hamed Abdel Bary & Samy El-Assaly (2002)
SYNTHESIS OF 1-(2-NAPHTHYLSULFONYL)PYRAZOLE-C-GLYCOSIDES, Nucleosides, Nucleotides and Nucleic Acids, 21:6-7,
469-475
To link to this article: http://dx.doi.org/10.1081/NCN-120014819
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 21, Nos. 6 & 7, pp. 469–475, 2002
SYNTHESIS OF
1-(2-NAPHTHYLSULFONYL)PYRAZOLE-
C-GLYCOSIDES
Abd El-Hamid Ismail,* Abdel Aleem Hassan Abdel Aleem,
Hamed Abdel Bary, and Samy El-Assaly
Chemistry Department, Faculty of Science, Menoufia University,
Shebin El-Koom, Egypt
ABSTRACT
2-Naphthylsulfonylhydrazine was reacted with aromatic aldehydes or
aldehydo sugars to give the corresponding hydrazones which undergo
Michael addition reactions with malononitrile or ethyl cyanoacetate to
form pyrazole derivatives.
INTRODUCTION
Some pyrazoles are biologically active and have been used as analgesic
anti-inflammatory,[1] chemical control substance for pharmacological char-
acterization of histamine receptors,[2] antibacterial activity against Escheri-
chia coli,[3] sedative and hypontic,[4] saluretic effect,[5] a good activity as
platelet aggregation inhibitor,[6] a prostaglandin synthetase inhibitor[7] and
an antirheumatic drug.[8]
*Fax: 20 48 235689
469
DOI: 10.1081=NCN-120014819
Copyright # 2002 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

470
EL-HAMID ISMAIL ET AL.
RESULTS AND DISCUSSION
The aim of the work in this paper is the synthesis of naphthylsulfo-
nylpyrazoles and naphthylsulfonylpyrazole-C-glycosides. We expect that the
naphthylsulfonyl group will increase the biological activity of the pyrazole
ring. Thus, treatment of 2-naphthalene sulphonyl chloride with hydrazine
hydrate produced 2-naphthyl-sulfonylhydrazine 1. Condensation of
2-naphthylsulfonylhydrazine 1 with equimolar amounts of aromatic alde-
hydes namely, benzaldehyde and anisaldehyde 2 in ethanol and in presence
of glacial acetic acid as a catalyst yielded the corresponding hydrazones 3.
2-Naphthyl-sulfonylhydrazones 3 were allowed to react with malononitrile
and/or ethyl cyanoacetate to afford 1-(2-naphthylsulfonyl)pyrazoles 5a^d
after purification by column chromatography. The reaction may be occur as
follows: Initial addition of active methylene moiety to the double bond of
hydrazones 3 affords an acyclic Michael adduct 4. The intermediate 4
cyclizes by internal addition to the cyano group or internal substitution at the
ester carbonyl followed by aromatization form pyrazole derivatives 5a^d
(Sch. 1).
Scheme 1.

1-(2-NAPHTHYLSULFONYL)PYRAZOLE-C-GLYCOSIDES
471
Scheme 2.
Pyrazole-C-glycosides were prepared via 1,3-dipolar cycloaddition
reaction of nitrilimines with acetylene derivatives[9,10] and methylacrylate.[11]
In our work 2-naphthylsulfonylhydrazine 1 was reacted with D-glucose,
D-mannose or D-xylose 6 to form the corresponding hydrazones 7. The
sugar-hydrazones 7 were reacted with malononitrile in ethanol and with a
catalytic amount of triethylamine via Michael addition to afford 1-(2-naph-
thylsulfonyl) pyrazole-C-glycosides 8 (Sch. 2).
EXPERIMENTAL
NMR spectra were recorded on a Bruker 250 FT NMR spectrometer,
TMS as internal standard. The silica gel (0.040–0.63 mm) used for CC was
purchased from Merck. Analytical TLC was performed on percolated TLC
sheets (Merk silica gel 60 F254 0.2 mm). Results of elemental analysis were in
acceptable range.
General Procedure for Compound 5a–d
A mixture of 2-naphthylsulfonylhydrazones 3 (1 mmole) and malono-
nitrile or ethyl cyanoacetate (1 mmole) in 10 mL of ethanol with a catalytic
amount of triethylamine was boiled under reflux 6 h. The solvent was eva-
porated under vacuum. The residue was purified by column chromatography
with chloroform=methanol (90:10, v=v) to give 5a^d.

472
EL-HAMID ISMAIL ET AL.
5-Amino-4-cyano-3-phenyl-1-(2-naphthylsulfonyl)pyrazole (5a)
1
Yield (54%); m.p. 182ꢀC. H-NMR (DMSO-dd): d 11.64 (s, 1H, NH),
8.53-7.39 (m, 9H, ArH); Anal. Calcd for C20H14N4O2S (374.42): C, 64.15; H,
3.27; N, 14.96. Found: C, 64.43; H, 3.76; N, 14.69.
5-Amino-4-cyano-3-(4-methyoxyphenyl)-1-(2-naphthylsulfonyl)pyrazole (5b)
1
Yield (56%); m.p. 188ꢀC. H-NMR (DMSO-dd): d 11.50 (s, 1H, NH),
9.23-8.65 (m, 10H, ArH), 3.59 (s, 3H, CH3O); Anal. Calcd for C21H16N4O3S
(404.45): C, 62.34; H, 3.99; N, 13.85. Found: C, 62.66; H, 4.20; N, 13.69.
4-Cyano-3-phenyl-1-(2-naphthylsulfonyl)pyrazole-5-one (5c)
1
Yield (45%); m.p. 191ꢀC. H NMR (DMSO-dd): d 11.53 (s, 1H, NH),
8.77-7.51 (m, 8H, ArH); Anal. Calcd for C20H13N3O3S (375.4): C, 63.99; H,
3.49; N, 11.19. Found: C, 63.72; H, 3.40; N, 11.45.
4-Cyano-3-(4-methoxyphenyl)-1-(2-naphthylsulfonyl)pyrazole-5-one (5d)
1
Yield (54%); m.p. 182ꢀC. H NMR (DMSO-dd): d 11.4 (s, 1H, NH),
8.50-7.86 (m, 11H, ArH), 3.11 (s, 3H, OCH3); Anal. Calcd for C21H15N3O4S
(404.43): C, 62.21; H, 3.72; N, 10.35. Found: C, 62.53; H, 3.60; N, 10.72.
General Procedure for Hydrazones 3a, b and 7a–c
A mixture of 2-naphthylsulfonylhydrazine (1 mmole) and D-Glucose,
D-Mannose, D-Xylose, benzaldehyde or anisaldehyde in 10 mL of ethanol
with a few drops of acetic acid was boiled under reflux for 1 h. After
concentration and cooling, the separated precipitate was filtered off and
crystallized from the appropriate solvents (3a, b from ethanol, 7a^c from
1,4-dioxane).
Benzaldehyde (2-naphthylsulfonyl)hydrazone (3a)
Yield (81%); m.p. 188ꢀC; Anal. Calcd for C17H14N2O2S (310.40): C,
65.79; H, 4.55; N, 9.03. Found: C, 75.61; H, 4.80; N, 9.11.

1-(2-NAPHTHYLSULFONYL)PYRAZOLE-C-GLYCOSIDES
473
Anisaldehyde (2-naphthylsulfonyl)hydrazone (3b)
Yield (70%); m.p. 192ꢀC; Anal. Calcd for C18H16N2O3S (340.36): C,
63.52; H, 4.74; N, 8.23. Found: C, 63.29; H, 4.81; N, 8.00.
D-Glucose 2-naphthylsulfonylhydrazone (7a)
Yield (76%); m.p. 173ꢀC; Anal. Calcd for C16H20N2O7S (384.4): C,
49.99; H, 5.24; N, 7.28. Found: C, 50.5; H, 5.40; N, 7.52.
D-Mannose 2-naphthylsulfonylhydrazone (7b)
Yield (72%); m.p. 179ꢀC; Anal. Calcd for C16N20N2O7S (384.4): C,
49.99; H, 5.25; N, 7.28. Found: C, 49.52; H, 5.00; N, 7.43.
D-Xylose 2-naphthylsulfonylhydrazone (7c)
Yield (73%); m.p. 168ꢀC; Anal. Calcd for C15H18N2O6S (354.37): C,
50.84; H, 5.12; N, 7.90. Found: C, 50.73; H, 5.30; N, 7.63.
General Procedure for Compound 8a–c
A mixture of 2-naphthylsulfonylhydrazones 7 (1 mmole) and mal-
ononitrile (1 mmole) in 10 mL absolute ethanol and 1 mL triethylamine was
boiled under reflux for 6 h. The solvent was evaporated under vacuum. The
residue was purified by column chromatography with chloroform/methanol
(90:10, v=v) to produce compounds 8a^c.
5-Amino-4-cyano-3-(D-gluco-1,2,3,4,5,pentahydroxypentyl)-1-(2-naphthyl
sulfonyl)pyrazole (8a)
1
Yield (53%); m.p. 180ꢀC; H-NMR (DMSO-dd): d 9.77 (s, 1H, NH),
8.55-7.60 (m, 7H, ArH), 5.67 (s, 1H, OH-10), 4.61 (s, 1H, H-10), 4.35 (m, 3H,
OH-20, OH-30 and OH-40), 4.01 (m, 1H, OH-50), 3.91 (m, 3H, H-20, H-30 and
H-40), 2.58 (m, 2 H,CH2OH). 13C NMR (DMSO-dd): d 136.58, 134.26, 131.65,
129.20, 128.81, 128.62, 128.44, 127.70, 127.36, 122.90 (C arom.),
0
0
112.11(CꢁN), 89.96 (C-10), 77.96 (C-2 ), 76.80 (C-30), 70.61 (C-40), 61.77 C5 );
Anal. Calcd for C19H20N4O7S (448.45): C, 50.88; H, 4.5; N, 12.49. Found: C,
50.71; H, 4.43; N, 12.62.

474
EL-HAMID ISMAIL ET AL.
5-Amino-4-cyano-3-(D-manno-1-1,2,3,4,5,pentahydroxypentyl)-(2-naphthyl
sulfonyl)pyrazole (8b)
1
Yield (55%); m.p. 178ꢀC; H-NMR (DMSO-dd): d 9.02 (s, 1H, NH);
8.52-7.58 (m, 7H, ArH) 4.70 (m, 2H, OH-10 and H-10) 4.58 (m, 3H, OH-20,
OH-30, OH-40), 3.98 (m, 1H, OH-50), 3.61 (m, 3H, H-20, H-30, H-40); 2.89 (m,
1 H, CH2OH). 13C NMR (DMSO-dd): d 136.51, 134.33, 131.70, 129.22,
128.85, 128.41, 127.75, 127.32, 124.94, 122.80 (C arom.), 112.33 (CꢁN),
91.71 (C-10), 76.80 (C-20), 70.28 (C-30), 69.40 (C-40), 66.75 (C-50); Anal. Calcd
for C19H20N4O7S (448.48): C, 50.88; H, 4.50; N, 12.49. Found: C, 50.90; H,
5.00; N, 12.55.
5-Amino-4-cyano-3-(D-xylo-1,2,3,4,tetrahydroxybutyl)-1-(2-naphthyl
sulfonyl)pyrazole (8c)
1
Yield (53%); m.p.; 188ꢀC; H-NMR (DMSO-dd): d 11.39 (s, 1H, NH),
8.51-7.86 (m, 7H, ArH), 5.40 (s, 1H, OH-10), 4.91 (s, 1H, H-10), 4.45 (m, 1H,
OH-20), 4.12 (m, 1H, OH-30), 3.94 (m, 1H, OH-40), 3.60 (m, 2H, H-20 and H-
30), 2.94 (m, 2H, CH2OH); 13C NMR (DMSO-dd): d 136.22, 134.39, 131.76,
129.29, 128.90, 127.84, 127.35, 123.07 (C arom.), 112.00 (CꢁN), 91.20 (C-10)
76.63 (C-20), 70.18 (C-30), 69.70 (C-40); Anal. Calcd for C18H18N4O6S
(418.43): C, 51.66; H, 4.34; N, 13.38. Found: C, 15.50; H, 4.46; N, 13.22.
ACKNOWLEDGMENT
The authors would like to express their thanks to DANIDA establish-
ment, Denmark, which supports the project ‘‘Development of new drugs
against Hepatitis’’ at the Chemistry Department, Faculty of Science,
Menoufia University for the laboratory facilities and spectroscopic
measurements.
REFERENCES
1. Credneer, K.; Tauscher, M.; Jozic, L.; Brenner, G. Salts of 5-methylpyrazole-3-
Carboxylic Acid with Basically Substituted Adenine Derivatives, Preparation
and Lipolysis Inhibitory Activity. Arzneim-Forsch. 1981, 31, 2096.
2. Bauer, V.L.; Dalalian, H.P.; Fanshawe, W.J.; Safir, R.S.; Tocus, E.C.; Boshart,
C.R. 4-[3(5)-Pyrazolyl]pyridinium salts. A New Class of Hypoglycemic Agents.
J. Med. Chem. 1968, 11, 981.
3. Kornet, M.J.; Garret, R.J. Synthesis of 1-phenyl-2(phenylcarbamoyl)pyrazoli-
dines as Potential Anticonvulsant Agents. J. Pharm. Sci. 1979, 68, 377.
4. Berger, J.C.; Iorio, L.C. Antianxiety Agents, Anticonvulsants, and Sedative-
hypnotics. Annu. Rep. Med. Chem. 1980, 15, 26.

1-(2-NAPHTHYLSULFONYL)PYRAZOLE-C-GLYCOSIDES
475
5. Kornet, M.J. New Local Anesthetics. 1 Esters of 1,2-diethyl-(3-hydroxy-
methyl) Pyrazolidine. J. Med. Chem. 1966, 9, 493.
6. Zeeb, B.; Goetz, N.; Ammermann, E.; Pommer, E.H. Ger. Pat. 1981,2926, 280.
7. Cassidy, P.E. Thermally Stable Polymer; Dekker: New York, 1980.
8. Buchanan, J.G.; Stobie, A.; Wightmann. C-Nucleosides Studies. Part 141. A
New Synthesis of Pyrazofurin. J. Chem. Soc. Perkin Trans. 1981, 1, 2374.
9. Tronchet, M.J.; Mlle, F.P. Helvetica Chemica Acta 1971, 54, 683. C-Glyco-
sides IV1). Mise en e
dipolar-1,3cocertee los de la re
aphile aceylenique.
´
vidence d’ un me
´
canisme concurrent de la cyclo-addition
´
´
action d’une azome
´
thine-imine avce un dipolar-
´
10. Tronchet, J.M.; Mlle, F.P. Helvetica Chemica Acta 1970, 53, 70. C-Glycosides
1); Synthese d’un analogue de la pyrazomycine.
11. Tronchet, J.M.; Tronchet, J.F.; Barbalat Rey, F. Synthesis of Pyrazole-C-
glycosides by 1,3-Dipolor Cycloaddition of Nitrilimines Formed by Lead Tetra-
acetateoxidationofp-NitrophenylhydrazonesofAldehydoSugars. Heterocycles
1993, 36 (4), 833.
Received February 7, 2002
Accepted June 12, 2002