Polyfunctional pyrazoles. 2. 1-Aryl-3-benzoyl-4-formyl- and 4-carboxypyrazoles

Article abstract of DOI:10.1023/A:1017651904859

Cyclization of 1-phenylpropane-1,2-dione monoarylhydrazones under Vilsmeier-Haack conditions gave 1-aryl-3-benzoyl-4-formylpyrazoles which were converted to 1-aryl-3-benzoyl-4-carboxyprazoles using potassium permanganate in aqueous pyridine medium.

Full text of DOI:10.1023/A:1017651904859

Chemistry of Heterocyclic Compounds, Vol. 37, No. 4, 2001
POLYFUNCTIONAL PYRAZOLES.
2*. 1-ARYL-3-BENZOYL-4-FORMYL-
AND 4-CARBOXYPYRAZOLES
M. K. Bratenko1, V. A. Chornous1, and M. V. Vovk2
Cyclization of 1-phenylpropane-1,2-dione monoarylhydrazones under Vilsmeier-Haack conditions gave
1-aryl-3-benzoyl-4-formylpyrazoles which were converted to 1-aryl-3-benzoyl-4-carboxypyrazoles
using potassium permanganate in aqueous pyridine medium.
Keywords: propiophenone hydrazones, carboxypyrazoles, formylpyrazoles, Vilsmeier-Haack reaction.
The method for preparing 3-aryl-4-formylpyrazoles [2, 3] by cyclizing aryl methyl ketone hydrazones
under Vilsmeier-Haack conditions can be successfully used in the synthesis of 4-formylpyrazoles which are
functionalized in the 3 position by heteroaromatic [4] and in the 1 position by a 2-cyanoethyl [1] substituent. In
this work we present the results of using the indicated reaction to prepare previously unknown 1-aryl-3-benzoyl-
4-formylpyrazoles and also the conversion of the latter to 4-carboxypyrazoles.
The reaction of propiophenone monoarylhydrazones 1a-d with a mixture of DMF and POCl3 leads to
the formation of the 1-aryl-3-benzoyl-4-formylpyrazoles 2a-d in 58-73% yield. Their structure was in agreement
with the results of analytical and spectroscopic measurements (Tables 1 and 2). The IR spectra of the aldehydes
2 in the region 1710-1715 cm-1 show some overlap of the C=O stretching absorptions for the formyl and benzoyl
1
groups. Their H NMR spectra show both signals for the aromatic substituent protons and also characteristic
formyl group (10.07-9.32 ppm) and pyrazole ring (9.11-9.32 ppm) proton singlets.
CHO
O
COOH
O
O
N
NHAr
DMF–POCl3
KMnO4
Ph
Ph
Ph
N
2a–d
N
N
N
CH3
Ar
Ar
3a–c
1a–d
1, 2 a Ar = C6H5; b Ar = 4-FC6H4; c Ar = 4-CH3C6H4; d Ar = 4-CH3OC6H4;
3 a Ar = C6H5; b Ar = 4-FC6H4; c Ar = 4-CH3OC6H4
_______
* For Communication 1, see [1].
__________________________________________________________________________________________
1
2
Bukovinian State Medicinal Academy, Chernovtsy 274000, Ukraine. Institute of Organic Chemistry,
National Academy of Sciences of Ukraine, Kiev 263660; e-mail: vovk@fuib.com, igoriv@users.univers.cv.ua.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 515-517, April, 2001. Original article
submitted May 6, 1999.
0009-3122/01/3704-0467$25.00©2001 Plenum Publishing Corporation
467

TABLE 1. Characteristics of Compounds Sythesized
Found, %
——————
Com-
Empirical
mp, °C
Yield, %
Calculated, %
pound formula
(ethanol)
C
H
N
C17H12N2O2
74.28
73.91
4.07
4.38
10.20
10.14
133-135
126-128
141-143
123-124
189-190
195-196
155-156
68
73
64
58
54
48
34
2a
2b
2c
2d
3a
3b
3c
C17H11FN2O2
C18H14N2O2
C18H14N2O3
C17H12N2O3
C17H11FN2O3
C18H14N2O4
69.03
3.67
9.28
69.38
3.77
9.52
75.04
74.77
4.51
4.86
9.73
9.65
70.69
4.76
9.01
70.58
4.57
9.15
70.21
69.86
4.33
4.10
9.18
9.58
66.13
3.31
9.17
65.80
3.54
9.03
67.31
67.08
4.59
4.34
8.45
8.69
TABLE 2. Spectroscopic Characteristics of Compounds 2a-d, 3a-c
Com-
pound
IR spectrum, ν, cm-1
1H NMR spectrum, δ, ppm
C=O (O–H)
CHO/COOH (1H)
5-H (1H)
Ar
1710
1715
1710
10.16
10.22
10.19
9.27
9.32
9.22
7.18-7.73 (10H, m)
7.47-8.18 (9H, m)
2a
2b
2c
7.12-7.63 (9H, m)
2.29 (3H, s, CH3)
1710
10.07
9.11
7.04.73 (9H, m)
3.79 (3H, s, CH3)
2d
1730 (2630)
1725 (2620)
1725 (2625)
12.69
12.53
12.79
9.03
8.96
9.08
7.12-7.90 (10H, m)
7.21-8.17 (9H, m)
3a
3b
3c
7.10-7.89 (9H, m)
3.82 (3H, s, CH3)
In order to obtain pyrazole carboxylic acids we have studied the oxidation of the pyrazole
carboxaldehydes 2 using potassium permanganate. It was found that the action of the latter in aqueous pyridine
medium on the aldehydes 2a,b,d gave satisfactory yields (34-54%) of the acids 3a-c (Tables 1 and 2). In the
case of aldehyde 2c the separation of pure reaction product could not be achieved since oxidation of the
aldehyde group occurred along with oxidation of the methyl group of the tolyl substituent.
1
The H NMR spectra of the 3-benzoylpyrazole-4-carboxylic acids, recorded in DMSO-d6 solvent,
identified protons in the aromatic substituents (7.04-8.18 ppm), the pyrazole ring (8.96-9.08 ppm), and the OH
group (12.53-17.79 ppm). In the IR spectra the OH group appeared as a broad band shifted to the region
2620-2630 cm-1, pointing to the presence of associated dimers which are formed through hydrogen bonding.
EXPERIMENTAL
1
IR spectra were recorded on a UR-20 instrument using KBr tablets. H NMR spectra were taken on a
Varian Gemini spectrometer (300 MHz) using DMSO-d6 solvent.
1-Phenylpropane-1,2-dione 2-Arylhydrazones (1a,c) were prepared by a known method [5] while
compounds 1b,d were obtained for the first time.
468

1-Phenylpropane-1,2-dione 2-(4-Fluorophenyl)hydrazone (1b). Yield 81%; mp 173-175°C. IR
spectrum, cm-1: 1660 (C=O), 3330 (N–H). Found, %: C 70.73; H 4.95; N 11.32. C15H13FN2O. Calculated, %:
C 70.30; H 5.11; N 10.93.
1-Phenylpropane-1,2-dione 2-(4-methoxyphenyl)hydrazone (1d). Yield 61%; mp 141-143°C.
IR spectrum, cm-1: 1665 (C=O), 3340 (N–H). Found, %: C 71.99; H 6.40; N 10.08. C16H16N2O2. Calculated, %:
C 71.62; H 6.01; N 10.44.
1-Aryl-3-benzoyl-4-formylpyrazoles (2a-d). POCl3 (20 g, 0.13 mol) was added with stirring to dry
DMF (20 ml) which had been cooled to 0°C. After 5 min, the hydrazone 1a-d (0.005 mol) in DMF (20 ml) was
added at such a rate that the temperature of the reaction mixture did not exceed 10°C. The product was then
stirred for a further 0.5 h at the same temperature, 1 h at room temperature, and finally 2.5 h at 60°C. After
cooling, the reaction mixture was poured into ice (200 g) and 10% NaOH was added to pH 7-8. The precipitated
product was filtered off, washed with water, dried, and recrystallized from ethanol.
1-Aryl-3-benzoyl-4-carboxypyrazoles (3a-c). A solution of KMnO4 (1.58 g, 0.01 mol) in water
(10 ml) was added with stirring to a suspension of aldehyde 2a,b,d (0.01 mol) in pyridine (10 ml) at room
temperature. The reaction mixture was stirred for 3 h, a solution of NaOH (1%, 50 ml) added, and stirring
continued for 2 h at 50°C. After cooling, the inorganic precipitate was filtered off and washed with water. The
combined filtrate and the water from the precipitate washing were acidified with HCl (6 N) to pH 4. The
precipitated 3 formed was filtered off, washed with water, dried, and crystallized from glacial acetic acid.
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469