Synthesis of 1-aryl-4-formylpyrazoles from acetaldehyde N-aryl-hydrazones by the Vilsmeier-Haack method

Full text of DOI:10.1007/s10593-006-0233-9

Chemistry of Heterocyclic Compounds, Vol. 42, No. 9, 2006
LETTERS TO THE EDITOR
SYNTHESIS OF 1-ARYL-4-FORMYL-
PYRAZOLES FROM ACETALDEHYDE N-ARYL-
HYDRAZONES BY THE VILSMEIER–HAACK METHOD
1
1
2
V. A. Chornous , M. K. Bratenko , and M. V. Vovk
Keywords: acetaldehyde N-arylhydrazones, 1-aryl-4-formylpyrazoles, Vilsmeier–Haack reagent.
Two methods are usually employed for the synthesis of 1-aryl-4-formylpyrazoles. The first is based on
formylation at position 4 of 1-arylpyrazoles under the conditions of the Vilsmeier–Haack reaction [1, 2] or
transformation of 1-aryl-4-chloropyrazoles according to Sommelet [3]. A second approach, supposing the
formation of the pyrazole ring in the presence of an aldehyde group, was tried in the case of the condensation of
triformylmethane with phenylhydrazine [4, 5].
Earlier [6-8] it was established that the formylation of the N-arylhydrazones of aryl methyl ketones by
the DMF–POCl system leads to the formation of 3-substituted 1-aryl-4-formylpyrazoles, whereas the analogous
3
reaction of the N,N-dialkylhydrazones of aromatic aldehydes leads to the 2-dialkylhydrazones of 1-arylglyoxals
[
9]. The N-monosubstituted hydrazones of aldehydes have not been investigated in the Vilsmeier–Haack
reaction.
We found that acetaldehyde N-arylhydrazones 1a-c undergo formylation when treated with the
Vilsmeier–Haack reagent with subsequent intramolecular cyclocondensation to the 1-aryl-4-formylpyrazoles
a-c.
2
CH=O
Me
HC
N
2
Me NCHO/POCl
2 3
N
N
NH
Ar
Ar
1
a–c
2a–c
1
, 2 a Ar = Ph, b Ar = 4-ClC
6
H
4
, c Ar = 4-MeC
6
H
4
1
13
The H and C NMR spectra were recorded on a Varian-Gemini spectrometer (300 and 75 MHz
respectively) in DMSO-d with TMS as internal standard.
6
_
_________________________________________________________________________________________
1
2
Bukovina State Medical University, Chernivtsi, Ukraine; e-mail: chva@chv.ukrpack.net. Institute of
Organic Chemistry, National Academy of Sciences of Ukraine, Kiev. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 9, pp. 1428-1429, September, 2006. Original article submitted May 24,
2
005.
1
242
0009-3122/06/4209-1242©2006 Springer Science+Business Media, Inc.

1
-Aryl-4-formylpyrazoles 2a-c. To DMF (40 ml), cooled to 0-5°C, we added with stirring POCl
.175 mol) over 0.5 h and then at the same temperature a solution of the hydrazone 1a-c (0.05 mol) in DMF
10 ml). The temperature of the reaction mixture was raised to 90°C, and the mixture was stirred for 3 h, cooled
3
(27 g,
0
(
to room temperature, poured into iced water (200 ml), and neutralized with crystalline sodium carbonate to pH 8.
The precipitate was filtered off, purified by chromatography on Al O (3:1 hexane–chloroform), and crystallized
2
3
from 50% ethanol.
-
1
1
Compound 2a. Yield 38%; mp 84-85°C (mp 85°C [3]). IR spectrum, ν, cm : 1700 (C=O). H NMR
spectrum, δ, ppm (J, Hz): 7.37 (1H, t, J = 7.8, H-4'); 7.52 (2H, t, J = 7.8, H-3',5'); 7.89 (2H, d, J = 7.9, H-2',6');
1
3
8
(
.19 (1H, s, H-5); 9.12 (1H, s, H-3); 9.91 (1H, s, CH=O). C NMR spectrum, δ, ppm: 119.82 (C-2',6'); 125.69
C-4); 128.03 (C-4'); 129.79 (C-3',5'); 130.04 (C-5); 139.14 (C-1'); 141.69 (C-3); 184.07 (CH=O). Found, %:
C 69.61; H 4.74; N 16.07. C H N O. Calculated, %: C 69.76; H 4.68; N 16.27.
1
0
8
2
-
1
1
Compound 2b. Yield 47%; mp 120-121°C. IR spectrum, ν, cm : 1705 (C=O). H NMR spectrum,
δ, ppm (J, Hz): 7.42 (2H, d, J = 8.0, H-2',6'); 7.64 (2H, d, J = 8.0, H-3',5'); 8.12 (1H, s, H-5); 8.40 (1H, s, H-3);
1
3
9
.93 (1H, s, CH=O). C NMR spectrum, δ, ppm: 120.92 (C-2',6'); 125.84 (C-4); 129.82 (C-3',5'); 129.96 (C-5);
1
33.64 (C-4'); 137.63 (C-1'); 141.82 (C-3); 183.85 (CH=O). Found, %: C 58.00; H 3.45; N 13.66. C H ClN O.
1
0
7
2
Calculated, %: C 58.13; H 3.41; N 13.56.
-
1
1
Compound 2c. Yield 42%; mp 89-90°C. IR spectrum, ν, cm : 1700 (C=O). H NMR spectrum, δ, ppm
(
(
J, Hz): 2.34 (3H, s, CH ); 7.33 (2H, d, J = 7.6, H-2',6'); 7.77 (2H, d, J = 7.6, H-3',5'); 8.23 (1H, s, H-5); 9.16
3
1
3
1H, s, H-3); 9.89 (1H, s, CH=O). C NMR spectrum, δ, ppm: 20.97 (CH ); 119.64 (C-2',6'); 125.80 (C-4);
3
1
30.53 (C-3',5'); 132.50 (C-5); 137.09 (C-1'); 137.62 (C-4'); 141.49 (C-3); 185.28 (CH=O). Found, %: C 70.80;
H 5.45; N 15.14. C H N O. Calculated, %: C 70.95; H 5.41; N 15.04.
1
1
10
2
REFERENCES
1
2
3
4
5
6
7
8
9
.
.
.
.
.
.
.
.
.
I. L. Finar and G. H. Lord, J. Chem. Soc., 1819 (1959).
I. L. Finar and G. H. Lord, J. Chem. Soc., 3314 (1959).
I. L. Finar and K. E. Godfrey, J. Chem. Soc., 2293 (1954).
K. Takagi, A. Bajati, and M. Hubert-Habart, Bull. Soc. Chim. France, 127, 660 (1990).
K. Takagi, A. Bajati, and M. Hubert-Habart, Heterocycles, 31, 1105 (1990).
M. A. Kira, M. O. Abdel-Raemann, and K. Z. Gadalla, Tetrahedron Lett., 10, 109 (1969).
K. Brehme, E. Grundemann, and M. Schneider, J. Pract. Chem., 342, 700 (2000).
M. K. Bratenko, I. N. Chernyuk, and M. V. Vovk, Zh. Org. Khim., 33, 1368 (1997).
R. Brehme, Chem. Ber., 123, 2039 (1990).
1
243