794
BADALYAN et al.
Scheme 2.
O
O
Me
H
Me
Me
NH
H
COOH
N+H
NH
+
+
N
Me
Me
Me
N
O−
N
COO−
O
H
XII
XIV
1
to H NMR) in 96% yield [4]. Heating the hydrolysis
products X–XII at 250°C (3 mmHg) led to the
formation of 4-formyl-1H-pyrazoles XIII–XIV in
yields of 30–60%.
propionate (Vb) was prepared similarly from 3-
methylpyrazole (8.2 g, 0.1 mol). Yield 16.2 g (96%),
ratio of 3:2, bp 94–97°C (1 mmHg). IR spectrum, ν,
cm–1: 1520 (ring), 1730 (C=O). Found, %: С 56.98; Н
7.21; N 16.71. С8Н12N2О2. Calculated, %: С 57.13; Н
7.19; N 16.66.
The lability of carboxyethyl group varies
considerably depending on the structure of the starting
pyrazole X–XII. The deprotection of 3-(4'-formyl-
3',5'-dimethylpyrazol-1'-yl)propionic acid XII showing
basic properties owing to pyrazole core [5] occurred
much better (yield 60%) [3] compared with
compounds X and XI. Under the same conditions
deprotection of compound X containing unsubstituted
pyrazole ring did not proceed. More rigid conditions
(300°C) led to complete tarring. In contrast, a mixture
of 3-(3'-methyl-4-formylpyrazol-1-yl)- and 3-(5'-
methyl-4-formylpyrazol-1-yl)propionic acids XIa and
XIb was converted into the corresponding NH-
formylpyrazoles XIIIa and XIIIb with a yield of 30%.
Methyl 3-(4'-formylpyrazol-1'-yl)propionic acid
(VII). A mixture of 14.4 g (0.1 mol) of methyl 3-
(pyrazol-1'-yl)propionate and 95 g (0.6 mol) of
dimethyl formamide was heated to 90°C with stirring.
Then to the mixture 30 g (0.2 mol) of phosphorus
oxychloride was carefully added, so that the
temperature of the reaction mixture did not exceed
120°C. The phosphorus oxychloride was added over
1 h, then the mixture was stirred at 100°C for 1 h. The
mixture was cooled with ice water, neutralized with
aqueous Na2CO3, extracted with chloroform, and dried
with magnesium sulfate. After distilling off the
solvent, the residue was distilled in vacuum. Yield
12.4 g (68%), bp 162°C (3 mmHg), nD20 1.5112. IR
These results can be explained by the fact that in
case of more alkylated pyrazole rings more basic
nitrogen atom is protonated with carboxyl hydrogen,
which largely contributes to the β-cleavage (Scheme 2).
1
spectrum, ν, cm–1: 1510 (ring), 1700 (CHO). H NMR
spectrum (DMSO-d6, 300 MHz), δ, ppm (J, Hz): 2.82 t
(2Н, CH2СН2, J 6.0), 3.60 s (3Н, ОCH3), 4.25 t (2Н,
NCH2, J 6.0), 7.30 s (1H, 3H), 7.50 s (1Н, 5-H), 9.80 s
(1Н, CHO). Found, %: С 52.70; Н 5.57; N 15.43.
С8Н10N2О3. Calculated, %: С 52.74; Н 5.53; N 15.38.
Methyl 3-(pyrazol-1'-yl)propionate (IV). A mix-
ture of 6.8 g (0.1 mol) of pyrazole I, 9.5 g (0.11 mol)
of methyl acrylate, and 0.1 g of hydroquinone was
heated for 8 h at 90°C. After removing an excess of
methyl acrylate the residue was distilled in vacuum.
Yield 12.3 g (80%), bp 81°C (1 mmHg), nD20 1.4751. IR
A mixture of methyl 3-(4'-formyl-3'-methyl-
pyrazol-1'-yl)propionate (VIIIa) and 3-(4'-formyl-
5'-methylpyrazol-1'-yl)propionate (VIIIb) was ob-
tained similarly from a mixture of Va, Vb (16.8 g,
0.1 mol). Yield 14 g (72 %), ratio of 3:2, bp 138–
141°C (1 mmHg). IR spectrum, ν, cm–1: 1530 (ring),
1650 (CHO). Found, %: С 55.28; Н 6.21; N 14.31.
С9Н12N2О3. Calculated, %: С 55.09; Н 6.16; N 14.28.
spectrum, ν, cm–1: 1510 (ring), 1730 (C=O). H NMR
1
spectrum (DMSO-d6, 300 MHz), δ, ppm (J, Hz): 2.84 t
(2Н, СН2СН2, J 6.2), 3.65 s (3H, ОCH3), 4.25 t (2Н,
NСН2, J 6.2), 6.13 d. d (1Н, 4-Н, J 2.3, 1.9), 7.32 d
(1Н, 3-Н, J 1.9), 7.53 d (1Н, 5-Н, J 2.3). Found, %: С
54.60; Н 6.50; N 18.24. С7Н10N2О2. Calculated, %: С
54.55; Н 6.54; N 18.17.
3-(4'-Formylpyrazol-1'-yl)propionic acid (X). A
mixture of 16.8 g (0.1 mol) of methyl 3-(4'-
formylpyrazol-1'-yl)propionate, 8 g (0.2 mol) NaOH
A mixture of methyl 3-(3'-methylpyrazol-1'-yl)-
propionate (Va) and 3-(5'-methylpyrazol-1'-yl)-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014