Synthesis of 1-(Arylsulfonyl)pyrazolo[1,5-a]pyridines

Full text of DOI:10.1134/S1070428012100223

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 10, pp. 1382–1383. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © S.A. Mamedov, L.M. Shakhgel’dieva, S.I. Mamedova, N.P. Ladokhina, I.Sh. Guseinov, 2012, published in Zhurnal Organicheskoi
Khimii, 2012, Vol. 48, No. 10, pp. 1385–1386.
SHORT
COMMUNICATIONS
Synthesis of 1-(Arylsulfonyl)pyrazolo[1,5-a]pyridines
S. A. Mamedov, L. M. Shakhgel’dieva, S. I. Mamedova, N. P. Ladokhina, and I. Sh. Guseinov
Guliyev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan,
pr. G. Dzhavida 29, Baku, Az1143 Azerbaijan
e-mail: iradam@rambler.ru
Received September 6, 2011
DOI: 10.1134/S1070428012100223
Among fused heterocyclic compounds, a specific
place is occupied by pyrazolopyridines which exhibit
a broad spectrum of biological activity. A promising
method for their preparation is based on 1,3-dipolar
cycloaddition to dipolarophiles. 1-Aminopyridinium
derivatives are 1,3-dipolar compounds capable of read-
ily undergoing heterocyclizations with formation of
pyrazolo- and triazolopyridines [1–3]. The reactivity of
different 1,3-dipolar structures was analyzed in [4, 5].
1,3-Dipolar compounds containing an N-arylsulfonyl
group have been poorly studied; methods of their
preparation are either laborious [6] or indirect [7].
load of dipolarophile affected the 1,3-dipolar heterocy-
clization process due to high reactivity of compounds
I. This may be illustrated by the reaction of com-
pounds Ia and Ib with chloroacetonitrile and benzoin
(Scheme 1).
By reaction of compounds Ia and Ib with 1,3-di-
phenylprop-2-en-1-one we obtained 1-(arylsulfonyl)-
pyrazolo[1,5-a]pyridines IIIa and IIIb containing
a carbonyl group on C3 (Scheme 2). Compounds IIIa
and IIIb are readily converted into enol tautomers IVa
and IVb. This is confirmed by their dissolution in 15–
20% alkali. The occurrence of keto–enol equilibrium
1
We examined 1,3-dipolar cycloaddition of 1-(aryl-
sulfonylamino)pyridinium salts to such dipolarophiles
as chloroacetonitrile, benzoin, and unsaturated ketones
and obtained the corresponding 1-(arylsulfonyl)pyra-
zolo[1,5-a]pyridines. We found that the reactivity of
dipolarophiles increases with rise in their strain and
upon introduction of electron-withdrawing substit-
uents. 1-(Arylsulfonylamino)pyridinium chlorides Ia
and Ib were synthesized by reaction of N-chloroarene-
sulfonamides (Chloramines B and T) with pyridines
[8]. Compounds Ia and Ib reacted with dipolarophiles,
e.g., with 2-(arylmethylidene)malononitriles to give
1-(arylsulfonyl)pyrazolo[1,5-a]pyridines II with high
regioselectivity [9]. Neither electronegativity nor steric
also followed from the IR and H NMR spectra. The
1H NMR spectrum of IIIb in DMSO-d6 contained
signals assignable to enolic hydroxy proton and
CHOH proton.
Scheme 2.
O
Ph
O
Ia, Ib
+
Ph
N
Ph
Ph
N
SO2Ar
IIIa, IIIb
HO
Ph
Scheme 1.
Ph
R
N
N
ClCH2CN
or PhCH(OH)C(O)Ph
SO2Ar
IVa, IVb
R'
N
SO2Ar
N
N
N
Cl–
H
SO2Ar
IIa–IId
1-(Arylsulfonyl)-1,3a-dihydropyrazolo[1,5-a]-
pyridin-3-amines IIa and IIb (general procedure).
Compound Ia or Ib, 0.05 mol, and chloroacetonitrile,
0.06 mol, were dissolved in 40 ml of ethanol, a solu-
Ia, Ib
R = NH2, R′ = H, Ar = Ph (a), 4-MeC6H4 (b); R = R′ = Ph,
Ar = Ph (c), 4-MeC6H4 (d).
1382

SYNTHESIS OF 1-(ARYLSULFONYL)PYRAZOLO[1,5-a]PYRIDINES
1383
tion of 0.12 mol of sodium hydroxide in ethanol was
added dropwise, and the mixture was heated under
reflux until complete precipitation of NaCl (4–4.5 h).
The mixture was cooled and filtered, the filtrate was
evaporated by half and cooled, and the precipitate was
filtered off and recrystallized from ethanol.
(OH), 1740 (C=O), 1450 and 1160 (SO2). Found, %:
C 70.38; H 5.63; N 6.59. C25H22N2O3S. Calculated, %:
C 70.55; H 5.11; N 6.36.
{1-(4-Methylphenylsulfonyl)-2-phenyl-1,2,3,3a-
tetrahydropyrazolo[1,5-a]pyridin-3-yl}phenylmeth-
1
anone (IIIb). Yield 69%, mp 194–196°C. H NMR
spectrum (DMSO-d6), δ, ppm: 2.2 t (CH3), 3.6 s (1H,
OH), 5.15 d (1H, CHO), 7.2 and 8.4 (10H, Harom), 7.6
(4H, Harom), 7.8 s and 8.8 s (2H each, pyridine), 8.15 s
(1H, pyrazole). Found, %: N 6.71. C27H24N2O3S. Cal-
culated, %: N 6.16.
Compound IIa. Yield 79%, mp 213–215°C. Found,
%: N 15.09. C13H11N3O2S. Calculated, %: N 15.43.
Compound IIb. Yield 71%, mp 228–230°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 1.1 t (CH3),
5.8 d (NH2), 6.8 s (2-H), 7.4 d (Harom); 7.6 s (2H), 8.0 d
(2H), 8.2 s (1H) (pyridine). Found, %: C 58.62;
H 5.68; N 14.26. C14H15N3O2S. Calculated, %:
C 58.08; H 5.22; N 14.56.
The IR spectra were recorded on UR-20 and IR-430
1
spectrometers, and the H NMR spectra were run on
a Bruker-250 spectrometer at 90 MHz.
1-(Arylsulfonyl)-3,4-diphenyl-1,3a-dihydropyra-
zolo[1,5-a]pyridines IIc and IId (general procedure).
Compound Ia or Ib, 0.05 mol, and benzoin, 0.05 mol,
were dissolved in 50 ml of ethanol, 10 ml of a 5 N so-
lution of potassium hydroxide was added, and the mix-
ture was heated for 3 h under reflux. The mixture was
cooled, and the precipitate was filtered off, washed
with water, dried, and recrystallized from ethanol.
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Compound IIc. Yield 72%, mp 185–186°C.
1H NMR spectrum (DMSO-d6), δ, ppm: 6.6–7.2 m
(10H, C6H5), 7.3–7.6 m (5H, C6H5SO2); 7.0–7.0 m
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%: N 7.22. C26H22N2O2S. Calculated, %: N 6.61.
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Compounds IIIa and IIIb were synthesized in
a similar way.
Phenyl{2-phenyl-1-phenylsulfonyl-1,2,3,3a-tetra-
hydropyrazolo[1,5-a]pyridin-3-yl}methanone (IIIa).
Yield 70%, mp 182–183°C. IR spectrum, ν, cm–1: 3440
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