Oxidation of 1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-carbaldehyde under phase-transfer catalysis

Full text of DOI:10.1134/S1070363214040343

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 4, pp. 796–798. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © V.I. Rstakyan, A.E. Akopyan, G.B. Zakaryan, H.S. Attaryan, G.V. Asratyan, 2014, published in Zhurnal Obshchei Khimii, 2014,
Vol. 84, No. 4, pp. 700–702.
LETTERS
TO THE EDITOR
Oxidation
of 1-(2-Hydroxyethyl)-3,5-dimethylpyrazole-4-carbaldehyde
under Phase-Transfer Catalysis
V. I. Rstakyan, A. E. Akopyan, G. B. Zakaryan, H. S. Attaryan, and G. V. Asratyan
Institute of Organic Chemistry, Scientific and Technical Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, pr. Azatutyan 26, Yerevan, 0014 Armenia
e-mail: vrstakyan@gmail.com
Received January 16, 2014
Keywords: pyrazole, oxidation, phase transfer catalysis, chemoselectivity
DOI: 10.1134/S1070363214040343
We have previously synthesized N-substituted
pyrazole-4-carboxylic acids from the corresponding
aldehydes under phase-transfer catalysis (PTC) [1, 2].
The chemoselective oxidation of the formyl group
occurred in these cases when the substituent at the
pyrazole nitrogen atom contained no hydroxy groups.
methyl moiety we introduced such protecting groups
into the organic molecule [3] which would prevent the
possibility of interaction of protecting groups with
other reactive centers of the molecule and with
reagents. When selecting protective groups, a proper
attention was paid to their convenient introduction into
the molecule, their stability in various reactions, and
ease of their removal.
The oxidation of 1-(2-hydroxyethyl)-3,5-dimethyl-
pyrazole-4-carbaldehyde
I
under phase-transfer
First experiments have shown that acetyl group
meets the above requirements.
catalysis (water–benzene–KMnO4–triethylbenzylam-
monium chloride) in the temperature range of 0–30°C
resulted in a mixture of two acids II, III in a ratio of
4 : 1 (according to 1H NMR spectroscopy) (Scheme 1).
Acylation of 1-(2-hydroxyethyl)-3,5-dimethyl-
pyrazole IV with vinyl acetate in the presence of a
catalytic amount of copper acetate afforded compound
V. The latter was readily subjected to Vilsmeier–
Haack formylation to give 2-(3,5-dimethyl-4-for-
mylpyrazol-1-yl)ethyl acetate VI. Then, compound VI
was oxidized with potassium permanganate under
phase-transfer catalysis. The resulting 1-(2-acetoxy-
ethyl)-3,5-dimethylpyrazole-4-carboxylic acid VII was
hydrolyzed with aqueous NaOH to afford the desired
3,5-Dimethyl-1-carboxymethylpyrazole-4-carboxylic
acid III was obtained in a 40% yield when the reaction
was performed at higher temperature (60°C) in the
presence of an excess of KMnO4.
For chemoselective oxidation of formyl group in
the molecule of 1-(2-hydroxyethyl)-3,5-dimethyl-
pyrazole-4-carbaldehyde I without affecting hydroxy-
Scheme 1.
O
O
O
H
HO
HO
KMnO4
PTC
N
N
+
N
N
N
N
OH
OH
O
OH
III
I
II
796

OXIDATION OF 1-(2-HYDROXYETHYL)-3,5-DIMETHYLPYRAZOLE-4-CARBALDEHYDE
797
Scheme 2.
O
H
O
POCl3
DMF
O
Cu+2
N
N
N
N
N
N
OH
O
O
O
O
IV
V
VI
O
O
OH
OH
(1) OH−
(2) HCl
KMnO4
PTC
N
N
N
N
O
OH
O
VII
II
1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-carboxylic
acid II (Scheme 2).
50 mL of water, 50 mL of benzene and 1 g Et3BnNCl
was added by portions 23.7 g of (0.15 mol) of
potassium permanganate with stirring, so that the
temperature of the reaction mixture did not exceed 30°C.
After addition of potassium permanganate, the mixture
was stirred for 12 h at room temperature. After
cooling, MnO2 was filtered off and washed with water.
Aqueous layer was extracted with diethyl ether. After
distilling off 2/3 of water, aqueous solution of py-
razolecarboxylic acid potassium salt was acidified with
hydrochloric acid. The precipitated crystals were
filtered off and dried. Yield 10.6 g (55%), mp 200°C.
IR spectrum, ν, cm–1: 1530 (ring), 1730 (C=O), 3200–
3400 (COOH). 1H NMR spectrum, δ, ppm: 2.00 s (3H,
OCH3), 2.30 s (3H, CH3), 2.48 s (3H, CH3), 4.17–4.22
m (2H, CH2), 4.29–4.34 m (2H, CH2), 17.72 br.s (1H,
COOH). Found, %: C 53.4; H 6.44; N 12.09.
C10H14N2O4. Calculated, %: C 53.09; H 6.19; N 12.38.
The structure and composition of compounds II, III
1
were confirmed by H NMR, IR spectroscopy and
elemental analysis.
3,5-Dimethyl-1-carboxymethylpyrazole-4-car-
boxylic acid (III). To a mixture of 16.8 g (0.1 mol) of
1-(2-hydroxyethyl)-3,5-dimethylpyrazole-4-carbalde-
hyde I, 50 mL of water, 50 mL of benzene, and 1 g of
Et3BnNCl was added by portions 79 g (0.5 mol) of
potassium permanganate with stirring at 60°C, so that
the temperature of the reaction mixture did not exceed
60°C. After addition of potassium permanganate, the
mixture was stirred for 2 h at 60°C. After cooling,
MnO2 was filtered off and washed with water.
Aqueous layer was extracted with diethyl ether. After
distilling off 2/3 of the amount of water, aqueous
solution of the potassium salt of the acid III was
acidified with hydrochloric acid. The precipitated
crystals were filtered off and dried. Yield 8 g (40.5%),
mp 210°C. IR spectrum, ν, cm–1: 1530 (ring), 1730
1-(2-Hydroxymethyl)-3,5-dimethylpyrazole-4-
carboxylic acid (II). A mixture of 18.4 g (0.1 mol) of
the acid VII, 8.0 g of sodium hydroxide and 50 mL of
water was stirred for 3 h at room temperature. Organic
compounds were removed from the reaction mixture
with chloroform. After distilling off 2/3 of water,
aqueous solution of pyrazolecarboxylic acid potassium
salt was acidified with hydrochloric acid. The
precipitated crystals were filtered off and dried. Yield
11.9 g (65%), mp 185°C. IR spectrum, ν, cm–1: 1530
(ring), 1570 (C=O), 3200–3400 (OH). 1H NMR
spectrum, δ, ppm (J, Hz): 2.21 s (3H, CH3), 2.53 s (3H,
1
(C=O), 3200–3400 (COOH). H NMR spectrum, δ,
ppm: 2.30 s (3H, CH3), 2.42 s (3H, CH3), 4.72 s (2H,
CH2), 11.82 br.s (2H, COOH). Found, %: C 48.21; H
5.38; N 14.38. C8H10N2O4. Calculated, %: C 48.48; H
5.05; N 14.14.
1-(2-Acetoxyethyl)-3,5-dimethylpyrazole-4-car-
boxylic acid (VII). To a mixture of 15.6 g (0.1 mol) of
2-(3,5-dimethyl-4-formylpyrazol-1-yl)ethyl acetate VI,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

798
RSTAKYAN et al.
2. Baltayan, A.H., Sahakyan, A.A., Attaryan, H.S., and
Asratyan, G.V., Russ. J. Gen. Chem., 2010, vol. 80,
no. 5, p. 1004. DOI: 10.1134/S1070363210050257.
3. McOmie, J.F.W., Protective Groups Inorganic
Chemistry, London; New York: Plenium Press, 1973,
p. 391.
4. Attaryan, H.S., Antanosyan, S.K., and Asratyan, G.V.,
Russ. J. Gen. Chem., 2008, vol. 78, no. 3, p. 508. DOI:
10.1134/S1070363208030298.
5. Baltayan, A.H., Rstakyan, V.I., Antanosyan, S.K.,
Kikoyan, F.S., Attaryan, H.S., and Asratyan, G.V.,
Russ. J. Gen. Chem., 2009, vol. 79, no. 4, p. 2417. DOI:
10.1134/S107036320911022X.
CH3), 3.72 t (2H, NCH2, J 5.6), 4.05 t (2H, CH2OH, J
5.6), 4.68 br.s (1H, OH), 11.83 br.s (1H, COOH).
Found, %: C 58.46; H 6.82; N 15.51. C8H12N2O3.
Calculated, %: C 58.17; H 6.52; N 15.21.
IR spectra were obtained on a Specord 75 IR
1
spectrophotometer from KCl pellets. H NMR spectra
were recorded on a Varian Mercury-300 (300 MHz) in
DMSO-d6. The starting pyrazoles IV–VI were
synthesized by known methods [4–6].
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