Synthesis of furylpyrazoles and pyrazolylindoles from 1-acyl-2-heteryl-1-nitroethenes [2]

Full text of DOI:10.1023/A:1021754118632

Chemistry of Heterocyclic Compounds, Vol. 38, No. 10, 2002
SYNTHESIS OF FURYLPYRAZOLES
AND PYRAZOLYLINDOLES FROM
1-ACYL-2-HETERYL-1-NITROETHENES
N. I. Aboskalova, V. M. Berestovitskaya, S. V. Bakhareva, and A. V. Fel'gendler
Keywords: gem-acylnitroethenes, hydrazine, pyrazolylindoles, furylpyrazoles, heterocyclization.
Many substituted furans and indoles have high pharmacological activity such as furacilin, furazolidon,
furazonal, indopan, mexamin, diazolin, and indomethacin [1].
The high reactivity of 1-acyl-2-heteryl-1-nitroethenes [2], which contain strongly electron-withdrawing
nitro and carbonyl functions at the double bond provides for the construction of new diheterocyclic structures.
We have shown that the reaction of 1-acetyl- and 1-benzoyl-2-heteryl-1-nitroethenes 1-4 with hydrazine
proceeds in ethanol at room temperature without catalyst with a nitroene ketone–hydrazine hydrate ratio 1:2 to
give heterocyclization products, namely, furyl- and indolylpyrazoles 5-8.
Het
CHC
Het
HN
N
X
5 – 8
NO2
NHNH2
Het–CH=C–C–X
H2NNH2
Het
Het
O
Het–CHB–CHA(NO2)COX
1–4
9
Het–CH=N–N=CH–Het
10
1, 5, 9 Het = furyl-2, 2, 3, 6, 7, 10 Het = 1-Me-Ind-3, 4, 8 Het = 1-Ac–Ind-3;
1, 3–5, 7–9 X = Ph, 2, 6 X = Me
Addition product 9 was isolated in the case of gem-acylnitroethenes of furan series 1. This finding
indicates that the initial attack of hydrazine on the 1-acyl-2-heteryl-1-nitroethenes studied is at the C=C double
bond. The feasibility of heterocyclization of the linear adducts formed in the first step is convincingly
demonstrated in the conversion of 9 into pyrazole 5 in ethanol in the presence of hydrazine.
__________________________________________________________________________________________
A. Hertzen Russian State Pedagogical University, St. Petersburg 191186, Russia; e-mail:
chemis@herzen.spb.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1462-1463,
October, 2002. Original article submitted July 4, 2002.
0009-3122/02/3810-1291$27.00©2002 Plenum Publishing Corporation
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An additional product, namely, the azine of 3-formyl-1-methylindole 10, is formed along with pyrazoles
6 and 7 in the case of gem-acetyl- and gem-benzoylnitroethenes 2 and 3, which contain an N-methylindole
substituent. In these cases, the bisadducts formed in the initial step from the monoadducts decompose with the
loss of acetyl- or benzoylnitromethine anions to give the azine.
The melting point of pyrazole 5 is close to the value reported by Musante [3]. The other substituted
pyrazoles 6-8 are obtained for the first time.
The structures of 5-10 were supported by elemental analysis, spectroscopy, and mass spectrometry. A
mixed probe of 10 with the product independently synthesized from 3-formyl-1-methylindole did not give a
depressed melting point.
The substituted pyrazoles synthesized contain two different heterocyclic pharmacophores, namely, furyl
or indole and pyrazole substituents, and hold potential biological activity.
1
5-(2-Furyl)-3-phenylpyrazole (5); mp 164-165°C (hexane) (173°C (ethanol) [3]). H NMR spectrum
(DMSO-d6), δ, ppm: 13.40 (1H, s, NH); 6.60-7.90 (9H, m, HC, Ph, furyl). Found, %: N 13.53. C13H10N2O.
Calculated, %: N 13.33.
1
1-Methyl-3-(3-methyl-5-pyrazolyl)indole (6); mp 188-189°C (ethanol). H NMR spectrum (CDCl3),
δ, ppm: 2.65 (3H, s, CH3); 3.85 (3H, s, NCH3); 7.00-8.00 (6H, m, HC, Ind). Found, %: N 19.89. C13H13N3.
Calculated, %: N 19.90.
1-Methyl-3-(3-phenyl-5-pyrazolyl)indole (7); mp 201-202°C (ethanol). Mass spectrum, m/z: 273
(M+·). 1H NMR spectrum (DMSO-d6), δ, ppm: 3.85 (3H, s, NCH3); 6.90-8.00 (11H, m, HC, Ph, Ind). Found, %:
N 15.23. C18H15N3. Calculated, %: N 15.38.
1-Acetyl-3-(3-phenyl-5-pyrazolyl)indole (8); mp 208-209°C (ethanol). 1H NMR spectrum (DMSO-d6),
δ, ppm: 2.70 (3H, s, COCH3); 8.45 (1H, s, NH); 6.90-8.05 (11H, m, HC, Ph, Ind). Found, %: N 13.74.
C19H15N3O. Calculated, %: N 13.95.
3-(2-Furyl)-3-hydrazino-2-nitro-1-phenyl-1-propanone (9); mp 111-112°C (ethanol). Mass spectrum,
m/z: 275 (M+·). 1H NMR spectrum (DMSO-d6): 5.14 (1H, s, CHB); 10.25 (1H, s, NH); 6.61 (2H, s, NH2); 7.30-
7.90 (9H, m, CHA, Ph, furyl). Found, %: C 56.55; H 4.81; N 15.33. C13H13N3O4. Calculated, %: C 56.72; H 4.72;
N 15.27.
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M. D. Mashkovskii, Drugs [in Russian], Torsing, Kharkov (1997), Vol. 1, pp. 112, 199, 315, Vol. 2,
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