Synthesis of 1-(2-Hydroxyethyl)-3,5-dimethyl-1H-pyrazole-4-carbaldehyde

Full text of DOI:10.1134/S1070363208030298

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 3, pp. 508–509. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © O.S. Attaryan, S.K. Antanosyan, G.V. Asratyan, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 3, pp. 523–524.
LETTERS
TO THE EDITOR
Synthesis of 1-(2-Hydroxyethyl)-3,5-dimethyl-1H-pyrazole-
4-carbaldehyde
O. S. Attaryana, S. K. Antanosyanb, and G. V. Asratyanb
a Armenian Institute of Applied Chemistry Ariak Ltd., Artashatskoe shosse 5/2, Erevan, 375053 Armenia
b Institute of Organic Chemistry, National Academy of Sciences of Armenia, Erevan, Armenia
Received August 24, 2007
DOI: 10.1134/S1070363208030298
We previously reported [1] that 1-(2-hydroxyethyl)-
3,5-dimethyl-1H-pyrazole (I) does not undergo
formylation according to Vilsmeier–Haack and that the
reaction occurs as substitution of the hydroxy group in
the 2-hydroxyethyl moiety by chlorine atom. We now
___________
propose a procedure for the synthesis of 1-(2-
hydroxyethyl)-3,5-dimethyl-1H-pyrazole-4-carbal-
dehyde (IV) from accessible 1-(2-hydroxyethyl)-3,5-
dimethylpyrazole (I) according to the following
scheme.
O
O
CH3
CH3
CH3
CH3
H
H
OH−
Ac2O
H+
POCl3
DMF
N
N
N
N
N
N
N
N
H3C
H3C
H3C
H3C
OH
OH
O
O
O
O
I
IV
___________
II
III
Acylation of I with acetic anhydride gives 1-(2-
acetoxyethyl)-3,5-dimethyl-1H-pyrazole (II) which
readily undergoes Vilsmeier–Haack formylation with
formation of 1-(2-acetoxyethyl)-3,5-dimethyl-1H-
pyrazole-4-carbaldehyde (III). Hydrolysis of III leads
___________
to
1-(2-hydroxyethyl)-3,5-dimethyl-1H-pyrazole-4-
carbaldehyde (IV). We also isolated from the reaction
mixture 1-(2-chloroethyl)-3,5-dimethyl-1H-pyrazole-
4-carbaldehyde (V, yield 7%); presumably, the latter
was formed as shown in the following scheme.
O
O
O
CH3
CH3
CH3
OH
CH3
H
H
H
H+
POCl3
POCl3
DMF
N
N
N
N
N
N
N
N
H3C
H3C
H3C
H3C
O
Cl
Cl
O
III
IV
V
VI
508

509
SYNTHESIS OF 1-(2-HYDROXYETHYL)-3,5-DIMETHYL-1H-PYRAZOLE-4-CARBALDEHYDE
The structure of compound V was proved by the 1H
NMR and IR spectra, elemental analysis, and
independent synthesis via formylation of 1-(2-
chloroethyl)-3,5-dimethyl-1H-pyrazole (VI).
(2H, NCH2, J = 5.9), 4.31 t (2H, CH2Cl, J = 5.9),
9.84 s (1H, CHO). Found, %: C 51.84; H 6.01; N
15.04; Cl 19.25. C8H11N2OCl. Calculated, %: C 51.34;
H 5.88; N 14.97; Cl 19.25.
Formylation of 1-(2-acetoxyethyl)-3,5-dimethyl-
1H-pyrazole (II). A mixture of 0.1 mol of compound
II and 0.6 mol of dimethylformamide was heated
under stirring to 90°C, and 0.2 mol of phosphoryl
chloride was carefully added dropwise under stirring,
maintaining the temperature not exceeding 120°C. The
mixture was cooled with ice water, neutralized with
aqueous sodium hydroxide, and extracted with
chloroform, the extract was dried over magnesium
sulfate, the solvent was distilled off, and the residue
was subjected to fractional distillation under reduced
pressure to isolate 15.3 g of a product with bp 150–
From the chloroform extract we isolated 11.76 g
(70%) of compound IV, bp 173°C (1 mm), mp 64–66°
C (from CCl4). IR spectrum, ν, cm–1: 1510 (ring), 1680
1
(C=O), 3200–3400 (OH). H NMR spectrum, δ, ppm
(J, Hz): 2.34 s (3H, 3-CH3), 2.52 s (3H, 5-CH3), 2.73 q
(2H, OCH2, J = 5.4), 4.02 t (2H, NCH2, J = 5.4), 4.68 t
(1H, OH, J = 5.4), 9.81 s (1H, CHO). Found, %: C
57.84; H 8.06; N 18.32. C8H12N2O2. Calculated, %: C
57.14; H 7.14; N 16.67.
1
The H NMR spectra were recorded on a Varian
Mercury-300 spectrometer (300 MHz). The IR spectra
were obtained on a Specord 75-IR instrument from
thin films. GLC analysis was performed on an LKhM-
8MD chromatograph equipped with a 1.5-m×3-mm
column packed with 10% of Carbowax-20M on
Inerton AW-HMDS (0.20–0.25 mm); carrier gas
helium, flow rate 50 ml min–1.
1
170°C (1 mm), nD20 = 1.5270. According to the H
NMR data, the product was compound IV containing
10% of 1-(2-chloroethyl)-3,5dimethyl-1H-pyrazole-4-
carbaldehyde (V), which was separated after
hydrolysis.
1-(2-Hydroxyethyl)-3,5-dimethyl-1H-pyrazole-4-
carbaldehyde (IV). A mixture of 21 g of the crude
product (see above), 4 g of sodium hydroxide, and 50 ml
of water was stirred for 3–4 h at 30°C. The mixture
was extracted first with diethyl ether and then with
chloroform, and the extracts were dried over
magnesium sulfate. After removal of the solvent, the
residue was subjected to fractional distillation under
reduced pressure. From the diethyl ether extract we
isolated 1.4 g of 1-(2-chloroethyl)-3,5-dimethyl-1H-
pyrazole-4-carbaldehyde (V), bp 135–140°C (1 mm),
nD20 = 1.5390. IR spectrum, ν, cm–1: 1530 (ring), 1660
Initial compounds I and II were synthesized
according to the procedures described in [2, 3].
REFERENCES
1. Attaryan, O.S., Antanosyan, S.K., Grigoryan, R.T.,
Martirosyan, S.S., and Matsoyan, S.G., Khim. Zh. Arm.,
2005, vol. 58, nos. 1–2, p. 131.
2. Asratyan, G.A., Attaryan, O.S., Pogosyan, A.S., Eliazyan, G.A.,
Darbinyan, E.G., and Matsoyan, S.G., Zh. Prikl. Khim.,
1986, no. 6, p. 1296.
1
(C=O), 640–650 (C–Cl). H NMR spectrum, δ, ppm,
3. US Patent no. 3063978, 1963; Ref. Zh., Khim., 1964,
no. 4, p. 219.
(J, Hz): 2.36 s (3H, 3-CH3), 2.54 s (3H, 5-CH3), 3.93 t
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008