Multicomponent reaction for synthesis of n-arylsulfonyl pyrazoles

Article abstract of DOI:10.1080/00397911.2013.771188

A synthesis of functionalized N-arylsulfonyl pyrazoles from the multicomponent reaction of arylsulfonyl hydrazones and dialkyl acetylenedicarboxylates in the presence nucleophilic compounds such as pyridine, isoquinoline, or triphenylphosphine, in good yields, is described. Taylor & Francis Group, LLC.

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Multicomponent Reaction for Synthesis
of N-Arylsulfonyl Pyrazoles
Gholamhossein Khalili a
a Chemistry Department , Islamic Azad University, Bushehr Branch ,
Bushehr , Iran
Accepted author version posted online: 03 Jul 2013.Published
online: 04 Sep 2013.
To cite this article: Gholamhossein Khalili (2013) Multicomponent Reaction for Synthesis of N-
Arylsulfonyl Pyrazoles, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 43:23, 3170-3174, DOI: 10.1080/00397911.2013.771188
To link to this article: http://dx.doi.org/10.1080/00397911.2013.771188
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Synthetic Communications1, 43: 3170–3174, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.771188
MULTICOMPONENT REACTION FOR SYNTHESIS
OF N-ARYLSULFONYL PYRAZOLES
Gholamhossein Khalili
Chemistry Department, Islamic Azad University, Bushehr Branch,
Bushehr, Iran
GRAPHICAL ABSTRACT
Abstract A synthesis of functionalized N-arylsulfonyl pyrazoles from the multicomponent
reaction of arylsulfonyl hydrazones and dialkyl acetylenedicarboxylates in the presence
nucleophilic compounds such as pyridine, isoquinoline, or triphenylphosphine, in good
yields, is described.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resources: Full
experimental and spectral details.]
Keywords Arylsulfonyl hydrazone; dialkyl acetylenedicarboxylate; N-arylsulfonyl
pyrazole; nucleophile
INTRODUCTION
The development of simple synthetic routes for novel medicinally active
compounds from readily available reagents is one of the major tasks in organic
synthesis. Pyrazoles and derivatives have attracted considerable attention because of
the wide variety of biological activities they exhibit, including antiviral, antitumor, anti-
bacterial, antipyretic, amoebicidal, anti-inflammatory, and amlgesic activities.[1–6]
A large number of methods have appeared describing syntheses of pyrazole com-
pounds. A general method for the synthesis of these species involves the condensation
of 1,3-diketones with hydrazine and hydrazine derivatives.[7,8] However, most electro-
philic functional group such as aldehydes, nitriles, esters, and alkyl halides do not
survive the transformation. Other methods for the synthesis of pyrazoles that do
not require 1,3-diketones have been reported.[9,10] We recently communicated
Received July 27, 2012.
Address correspondence to Gholamhossein Khalili, Chemistry Department, Islamic Azad
University, Bushehr Branch, P.O. Box 7519619555, Bushehr, Iran. E-mail: khalili_gh1352@yahoo.com
3170

SYNTHESIS OF N-ARYLSULFONYL PYRAZOLES
3171
diasteroselective and regioselective multicomponent one-pot synthesis of substituted
pyrazoles.[11,12] The development of simple methods that overcome the previous
drawbacks is strongly desirable.
We report an efficient synthetic route to polysubstituted pyrazoles using aryl-
sulfonyl hydrazones,[13–17] an efficient, novel, and higly simple procedure for the
direct synthesis of N-arylsulfonyl pyrazoles from acetylenic esters and arylsulfonyl
hydrazones.[18,19] in presence of nucleophilic compounds such as isoquinoline,
pyridine, or triphenylphosphine.
RESULTS AND DISCUSSION
We report a mild procedure for the synthesis of N-arylsulfonyl pyrazoles 3
from the reaction of the zwitterion arising from the addition of nucleophiles
such as isoquinoline, pyridine, or triphenylphosphine to activated acetylenes 1 with
arylsulfonyl hydrazones 2 (Scheme 1). After screening with various amounts of
nucleophilic compounds, the best results were obtained in CH2Cl2 at rt for 15 h in
the presence of stoichiometric amounts of isoquinoline, pyridine, or triphenylpho-
sphine. Decreasing the amount of nucleophiles to a catalytic amount resulted in
incomplete consumption of arylsulfonyl hydrazones.
All the compounds are stable crystalline solids whose structure is fully sup-
1
ported by elemental analyses and infrared (IR), high-field H NMR and 13C NMR
spectroscopy and mass spectrometry data. The IR spectrum of compound 3a showed
characteristic absorption at 1730 cmꢀ1 corresponding to the ester carbonyl moiety
Scheme 1. Synthesis of N-arylsulfonyl pyrazoles.

3172
G. KHALILI
Scheme 2. Proposed mechanism pathway.
1
and at 1196 and 1274 cmꢀ1 due to the sulfonyl group. The H NMR spectrum
exhibited three sharp singlets at 2.43, 3.62, and 3.73 for a methyl and methoxylcarbo-
nyl group protons, respectively. The doublet and multiplet signals in the range of
7.34–7.92 ppm for aromatic moiety and molecular ion peak m=z at 414 in the mass
spectrum confirm the proposed structure as dimethyl 1-[(4-methylphenyl)sulfonyl]-
3-phenyl-1H-pyrazole-4,5-dicarboxylate.
A mechanistic rationalization for the reaction is provided in Scheme 2.
Presumably, the zwitterionic intermediate 4 formed from nucleophile (isoquinoline,
pyridine, or PPh3) and dialkyl acetylenedicarboxylate is protonated by 2 to furnish
intermediates 5 and 6, which undergo [1,3]-cycloaddition to generate 7. This
intermediate is converted into final product 3 via elimination of nucleophile and
aromatization.
In conclution, we have devised a novel reaction for the synthesis of a variety of
N-arylsulfonylpyrazole derivatives under mild conditions. The presence of trans-
formable functionalities in these products makes them potentially valuable from
the vantage point of further synthetic manipulations. It is noteworthy that pyrazole
derivatives are often useful as pharmaceuticals and agrochemicals.
EXPERIMENTAL
Compounds 1 and dialkyl actylenedicarboxylate were obtained commercially
and used without further purification. Compounds 2 were prepared according to
Ref. 20 and measured as follows: Mp, Electrothermal-9100 apparatus; IR spectra,

SYNTHESIS OF N-ARYLSULFONYL PYRAZOLES
3173
ꢀ1
;
1H and 13C NMR spectra: Bruker
ꢀ
Shimadzu-IR-460 spectrometer; v in cm
DRX-400 Avance instrument at 400.1 and 100.6 MHz, respectively; d in ppm; J in
hertz: MS; Finnigan-MAT-8430EI-MS mass spectrometer, at 70 eV in m=z (rel. %);
and elemental analyses, Vario EL III CHNO elemental analyzer.
General Procedure for Preparation of Substituted Dialkyl
3-(Aryl)-1-arylsulfonyl-1H-pyrazoles (3a–3h)
A solution of arylsulfonyl hydrazone 2 (1 mmol) and nucleophile (1 mmol) in
dichloromethne (4 ml) was cooled to 0–5ꢁC. A solution of dialkyl acetylenedicabox-
ylate 1 (1 mmol) in CH2Cl2 (2 ml) was added to this, and the reaction mixture was
stirred for 15 h at rt. The organic solvent evaporated under reduced pressure. The
resulting residue was purified by silica-gel column chromatography (6:1 hexane=ethyl
acetate) and recrystallized from diethyl ether to afford the crystalline product.
Dimethyl 1-[(4-Methylphenyl) sulfonyl]-3-phenyl-1H-pyrazole-4,5-
dicarboxylate (3a)
Yellow powder, mp: 124–126ꢁC, yield: 0.33 g (82%).IR (KBr): 2948, 1730,
1444, 1347, 1274, 1196, 1031, 769, 680, 568. 1H NMR (400.1 MHz, CDCl3):
dH ¼ 2.43 (3H,s, Me); 3.62 (3H,s, MeO); 3.73 (3H,s, MeO); 7.34 (5H,m, 5CH);
7.59 (2H,m, 2CH); 7.92 (2H, d, J ¼ 8.4 Hz, 2CH).13C NMR(100.6 MHz, CDCl3):
dC ¼ 21.6 (Me); 52.5 (MeO); 53.2 (MeO); 127.4 (2CH); 128.5 (2CH); 128.9 (2CH);
129.1 (2CH); 130.1 (CH); 133.1 (C); 133.6 (C); 134.4 (C); 135.2 (C); 143.0 (C);
þ
=
=
144.2 (C); 162.5 (C O); 163.2 (C O). EI-MS: 414 (M , 3), 229 (100), 201 (75),
155 (35), 91 (90), 77 (40), 65 (30). Anal. calc. for C20H18N2O6S (414.43): C, 57.96;
H, 4.38; N, 6.76%. Found: C, 57.37; H, 4.69; N 6.46%.
SUPPLEMENTARY MATERIAL
1
Full experimental details and H and 13C NMR spectra can be found via the
Supplementary Content section of this article’s Web page.
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