Novel synthesis of 5-amino-1-arylsulfonyl-4-pyrazolin-3-ones as a new class of N-sulfonylated pyrazoles

Article abstract of DOI:10.1039/a800465j

A novel synthesis of 5-amino-1-arylsulfonyl-4-pyrazolin-3-ones via intramolecular cyclization of cyanoaceto-N-arylsulfonylhydrazides is reported and the synthetic potential of the method is demonstrated.

Full text of DOI:10.1039/a800465j

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384 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 384^385y
Novel Synthesis of 5-Amino-1-arylsulfonyl-
4-pyrazolin-3-ones as a New Class of
N-Sulfonylated Pyrazolesy
Galal H. Elgemeie*a and Nadia H. Metwallyb
aChemistry Department, Faculty of Science, Helwan University, Helwan, Cairo, Egypt
bChemistry Department, Faculty of Science, Cairo University, Giza, Egypt
A novel synthesis of 5-amino-1-arylsulfonyl-4-pyrazolin-3-ones via intramolecular cyclization of cyanoaceto-
N-arylsulfonylhydrazides is reported and the synthetic potential of the method is demonstrated.
Recent reports from our laboratory and others have dem-
onstrated the e¡ectiveness of a variety of N-sulfonylated
heterocycles and other antimetabolites as antiplastic agents
Compounds 2 on re£uxing in ethanol containing catalytic
amounts of piperidine undergo intramolecular cyclization
to give the 5-amino-1-arylsulfonyl-4-pyrazolin-3-ones 4 or
the tautomeric 5-amino-1-arylsulfonyl-3-hydroxypyrazole
structures 5. The hydroxy form 5 would be expected to
be more stable, because of the weakened basicity of the ring
nitrogen at the 2 position, in turn arising from the adjacent
heteroatom and the oxygen at the 3 position, however
spectral studies indicated the presence of the NH tautomer
in solution for all products, thus, the 13C NMR for 4a
revealed a signal at d 170.81 assigned to a carbonyl carbon
atom, and its 1H NMR revealed a broad singlet at d 10.00
assigned to an NH group (D2O exchangeable). No signi¢-
cant amounts of the alternative tautomer 5 could be
detected in solution.
5
in a number of experimental murine tumor systems.1
These compounds have been shown to cause inhibition
of thymidine and uridine incorporation into DNA and
RNA and appear to constitute
a new class of anti-
metabolites. It was of interest to study their stereostructure
and evaluate the e¡ects of various structural modi¢cations
on biological activity. Recently, N-carboxyamidated
pyrazoles
were
prepared
in
low
yields
from
cyanoaceto-N-arylaminohydrazides.6 The present investi-
gation reports a new, one-step synthesis of N-sulfonylated
pyrazoles via intramolecular cyclization of cyanoaceto-
N-arylsulfonylhydrazides.
O
O
Experimental
O
ArSO2Cl
EtOH
EtOH/pip.
heat
HN
O
C
N
HN
O
Melting points were uncorrected. IR spectra were obtained (KBr
disc) on a Pye Unicam Spectra-1000 spectrophotometer, 1H and
13C NMR spectra on Wilmad 270 MHz or Varian 400 MHz
spectrometers for solutions in DMSO-d6 using SiMe4 as internal stan-
dard and mass spectra on a Varian MAT 112 spectrometer. Analytical
data were obtained from the Microanalytical Data Center at Cairo
University.
NC
NH2
NH
NH
N
N
H
S
O
S
O
Ar
Ar
1
2a–f
3a–f
General
Procedure
for
Arylsulfonylcyanoacetohydrazides
(0.01 mol) and
HO
O
2a^f.öA mixture of cyanoacetohydrazide
1
arylsulfonyl chloride (0.01 mol) in ethanol (30 ml) was stirred at
room temperature for 24 h. The resulting solid product was ¢ltered
o¡ and crystallized from EtOH.
N
O
HN
O
NH2
NH2
N
N
1
S
O
S
O
2a: mp 170 8C, yield 88%. IR (KBr): v/cm 3407, 3284 (NH),
2215 (CN, s), 1686 (CˆO, s). 1H NMR (DMSO-d6): d 3.63 (s,
2H, CH2), 7.56^7.86 (m, 5H, C6H5†, 10.11 (s, br, 1H, NH), 10.40
(s, br, 1H, NH) m=z ˆ 239 (Found: C, 45.36: H, 4.0; N, 17.75; S,
13.60. Calc. for C9H9N3O3S: C, 45.16; H, 3.79; N, 17.56; S, 13.40%).
2b: mp 222^224 8C, yield 95%. IR (KBr): v/cm 1 3400, 3320 (NH),
2220 (CN, s), 1688 (CˆO, s). 1H NMR (DMSO-d6): d 3.81 (s, 2H,
CH2), 7.50^8.10 (m, 4H, C6H4†, 10.23 (s, br, 1H, NH), 10.93 (s,
br, 1H, NH) m=z ˆ 274 (Found: C, 39.67; H, 2.75; N, 15.55; S, 11.90.
Calc. for C9H8ClN3O3S: C, 39.47; H, 2.94; N, 15.35; S, 11.71%).
Ar
Ar
5a–f
4a–f
2,4 Ar
a
b
c
d
e
f
Ph
C6H4-4-Cl
C6H4-4-Br
C6H4-4-Me
C6H4-4-OMe
C6H4-4-NO2
1
2c: mp 211 8C, yield 92%. IR (KBr): v/cm 3380, 3300 (NH),
2221 (CN, s), 1687 (CˆO, s). 1H NMR (DMSO-d6): d 3.71 (s,
2H, CH2), 7.44^8.15 (m, 4H, C6H4†, 10.23 (s, br, 1H, NH), 11.05
(s, br, 1H, NH) m=z ˆ 318 (Found: C, 33.74; H, 2.72; N, 13.00; S,
10.27. Calc. for C9H8BrN3O3S: C, 33.94; H, 2.53; N, 13.20; S,
10.07%).
Thus, it has been found that cyanoacetohydrazide 1 reacts
with arylsulfonyl chloride in ethanol to a¡ord the corre-
sponding cyanoaceto-N-arylsulfonylhydrazides 2 in good
yields. The structures of 2 were established and con¢rmed
on the basis of their elemental analysis and spectral data
(mass, IR, 1H NMR). The analytical data for 2a revealed
1
2d: mp 180 8C, yield 85%. IR (KBr): v/cm 3380, 3220 (NH),
2220 (CN, s), 1680 (CˆO, s). 1H NMR (DMSO-d6): d 2.34 (s,
3H, CH3), 3.65 (s, 2H, CH2†, 7.11^7.77 (m, 4H, C6H4), 10.77 (s,
br, 1H, NH), 11.21 (s, br, 1H, NH). m=z ˆ 253 (Found: C, 47.60;
H, 4.16; N, 16.80; S, 12.46. Calc. for C10H11N3O3S: C, 47.40; H, 4.37;
N, 16.59; S, 12.66%).
a molecular formula C9H9N3O3S (M , m/z 239), 1H NMR
‡
spectroscopy was used to con¢rm this structure. Thus, a
band at d 3.63 was assignable to the CH2 group, a multiplet
at d 7.56^7.86 to aromatic protons and two broad singlets at
d 10.11 and 10.40 to two NH groups (D2O exchangeable).
1
2e: mp 166 8C, yield 90%. IR (KBr): v/cm 3480, 3400 3220
(NH), 2220 (CN, s), 1687 (CˆO, s). 1H NMR (DMSO-d6): d 3.62
(s, 2H, CH2), 3.74 (s, 3H, OCH3†, 7.34^7.82 (m, 4H, C6H4), 11.21
(s, br, 1H, NH), 11.68 (s, br, 1H, NH). m=z ˆ 269 (Found: C, 44.77;
H, 4.31; N, 15.42; S, 11.71. Calc. for C10H11N3O4S: C, 44.55; H, 4.11;
N, 15.61; S, 11.91%).
* To receive any correspondence.
1
y This is a Short Paper as de¢ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is
therefore no corresponding material in J. Chem. Research (M).
2f: mp 231^232 8C, yield 93%. IR (KBr): v/cm 3370, 3300 3250
(NH), 2221 (CN, s), 1688 (CˆO, s). 1H NMR (DMSO-d6): d 3.64
(s, 2H, CH2), 7.38^8.02 (m, 4H, C6H4†, 10.81 (s, br, 1H, NH) 11.31

View Article Online
J. CHEM. RESEARCH (S), 1999 385
1
(s, br, 1H, NH), m=z ˆ 284 (Found: C, 38.22; H, 2.64; N, 19.91; S,
11.48. Calc. for C9H8N4O5S: C, 38.01; H, 2.83; N, 19.71; S, 11.28%).
General Procedure for 5-Amino-1-arylsulfonyl-4-pyrazolin-3-ones
4a^f.öA solution of 2a^f (0.001 mol) in 30 ml EtOH and piperidine
(0.3 ml) was re£uxed for 3 h. The resulting solid product was ¢ltered
o¡ and crystallized from EtOH^1,4-dioxane.
4e: mp 217 8C, yield 91%. IR (KBr): v/cm 3620, 3580, 3410
(NH2, NH), 1618 (CO, s). 1H NMR (DMSO-d6): d 3.78 (s, 3H,
OCH3), 4.51 (s, 1H, CH), 6.70 (s, br, 2H, NH2), 7.30^7.89 (m,
4H, C6H4†, 11.12 (s, br, 1H, NH). m=z ˆ 269 (Found: C, 44.77;
H, 4.31; N, 15.42; S, 11.71. Calc. for C10H11N3O4S: C, 44.58; H, 4.11;
N, 15.61; S, 11.91(%).
1
4a: mp 208^210 8C, yield 85%. IR (KBr): v/cm 3480, 3400
4f: mp 260^262 8C, yield 88%. IR (KBr): v/cm 1 3560, 3485, 3400
(NH2, NH), 1628 (CO, s), cm 1. 1H NMR (DMSO-d6): d 4.55 (s, 1H,
CH), 6.66 (s, br, 2H, NH2), 7.41^7.92 (m, 4H, C6H4), 11.0 (s, br, 1H,
NH). m=z ˆ 284 (Found: C, 38.22; H, 2.64; N, 19.91; S, 11.48. Calc.
for C9H8N4O5S: C, 38.01; H, 2.83; N, 19.71; S, 11.28%).
(NH2, NH), 1615 (CO, s). 1H NMR (DMSO-d6): d 4.34 (s, 1H, CH),
6.78 (s, br, 2H, NH2), 7.63^7.85 (m, 5H, C6H5), 10.00 (s, br, 1H, NH),
13C NMR (DMSO-d6): d 79.17 (C-4), 128.5^134.85 (ArC), 158.94
(C-5), 170.81 (C-3) m=z ˆ 239 (Found: 45.36; H, 4.0; N, 17.36; S,
13.60. Calc. for C9H9N3O3S: C, 45.16; H, 3.79; N, 17.56; S, 13.40%).
4b: mp 255^256 8C, yield 90%. IR (KBr): v/cm 1 3600, 3520, 3400
(NH2, NH), 1620 (CO, s). 1H NMR (DMSO-d6): d 4.45 (s, 1H, CH),
6.51 (s, br, 2H, NH2), 7.50^7.90 (m, 4H, C6H4), 10.62 (s, br, 1H, NH),
13C NMR (DMSO-d6): d 80.01 (C-4), 127.8^133.92 (ArC), 158.53
(C-5), 170.25 (C-3) m=z ˆ 274 (Found: C, 39.27; H, 2.75; N, 15.15;
S, 11.90. Calc. for C9H8ClN3O3S: C, 39.47; H, 2.94; N, 15.35; S,
11.71%).
Received, 16th January 1998; Accepted, 2nd March 1999
Paper E/8/00465J
References
1
2
3
4
5
G. E. H. Elgemeie, A. M. E. Attia, D. S. Farag and S. M.
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4c: mp 240^242 8C, yield 92%. IR (KBr): v/cm 1 3820, 3300 (NH2,
NH), 1625 (CO, s). 1H NMR (DMSO-d6): d 4.41 (s, 1H, CH), 6.81 (s,
br, 2H, NH2), 7.34^7.80 (m, 4H, C6H4), 10.82 (s, br, 1H, NH),
13C NMR (DMSO-d6): d 79.73 (C-4), 128.07^133.82 (ArC), 159.23
(C-5), 171.25 (C-3) m=z ˆ 318 (Found: C, 33.74; H, 2.32; N, 13.40;
S, 10.27. Calc. for C9H8BrN3O3S: C, 33.94; H, 2.53; N, 13.20; S,
10.07%).
1
4d: mp 203 8C, yield 84%. IR (KBr): v/cm 3550, 3500, 3420
(NH2, NH), 1630 (CO, s). 1H NMR (DMSO-d6): d 2.34 (s, 3H, CH3),
4.48 (s, 1H, CH), 6.88 (s, br, 2H, NH2), 7.41^7.92 (m, 4H, C6H4†,
10.85 (s, br, 1H, NH). 13C NMR (DMSO-d6): d 18.22 (CH3) 77.82
(C-4), 127.23^133.24 (ArC), 156.23 (C-5), 169.89 (C-3) m=z ˆ 253
(Found: C, 47.20; H, 4.16; N, 16.39; S, 12.46. Calc. for
C10H11N3O3S: C, 47.40; H, 4.37; N, 16.59; S, 12.66%).
6