Bromination of 1,3-dimethyl- and 1,5-dimethyl-1H-pyrazole-4-carboxylic acids [1]

Full text of DOI:10.1134/S1070363207020193

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 2, pp. 307 308.
Pleiades Publishing, Ltd., 2007.
Original Russian Text O.S. Attaryan, G.A. Akopyan, K.S. Badalyan, G.V. Asratyan, 2007, published in Zhurnal Obshchei Khimii, 2007, Vol. 77, No. 2,
pp. 335 336.
LETTERS
TO THE EDITOR
Bromination of 1,3-Dimethyl-
and 1,5-Dimethyl-1H-pyrazole-4-carboxylic Acids
O. S. Attaryan, G. A. Akopyan, K. S. Badalyan, and G. V. Asratyan
Institute of Applied Chemistry, National Academy of Sciences of Armenia,
Artashatskoe sh. 5/2, Erevan, 375053 Armenia
Received November 22, 2006
DOI: 10.1134/S1070363207020193
Bromination is a common method for preparing
pyrazole bromo derivatives; therewith, no catalysts
are required. In anhydrous organic solvents, the
product forms as hydrobromide. However, if the pro-
cess is carried out with the conjugate base of pyrazole,
4-bromopyrazole is isolated directly [1]. With excess
bromine, dibromo and tribromo derivatives can form
[2].
followed by decarboxylation of products III, IV
would allow us to prepare 5-bromo-1,3-and 3-bromo-
1,5-dimethyl-1H-pyrazoles (V, VI).
However, upon bromination of acids I, II we iso-
lated from the reaction mixtures 4-bromo derivatives
VII, VIII (yield 70 80%), instead of desired products
III, IV.
According to [3, 4], N-methyl(ethyl)pyrazole-3(5)-
carboxylic acids are brominated exclusively at the
4 position of the pyrazole ring.
The structure of compounds VII, VIII was proved
by their independent synthesis via bromination of
1,3-dimethyl- and 1,5-dimethylpyrazoles, as well as
1
We expected that bromination of 1,3-dimethyl- and
by H NMR and IR spectroscopy, GLC, and elemental
1,5-dimethyl-1H-pyrazole-4-carboxylic acids (I, II)
analysis.
CH3
Br
N
CH3
CH3
HOOC
Br
N
CH3
HOOC
N
N
Br
CH3
VII
N
N
N
N
CH3
CH3
III
V
CH3
I
(1) Br2 (2) OH
HOOC
H3C
N
N
Br
Br
HOOC
H3C
Br
H3C
CH3
N
N
H3C
II
N
N
N
N
CH3
CH3
CH3
IV
VI
VIII
307

308
ATTARYAN et al.
d240 1.5059 [5]. IR spectrum, , cm : 1530 (pyrazole
1
The IR spectra were recorded on a Specord 75 UR
1
spectrophotometer in KBr pellets or in thin films. The
1H NMR spectra were measured on a Varian Mercury
instrument (300 MHz) in DMSO-d6 solutions.
ring). H NMR spectrum, , ppm: 2.25 s (3H, 3-CH3),
3.80 s (3H, N CH3), 7.21 s (1H, 5-H). Found, %:
C 34.49; H 4.42; Br 45.93; N 16.51. C5H7BrN2. Cal-
culated, %: C 34.31; H 4.02; Br 45.65; N 16.00.
Starting pyrazoles I and III were prepared as
described in [6, 7]: I, mp 182 C; II, mp 186 C.
REFERENCES
4-Bromo-1,3-dimethyl-1H-pyrazole (VII). To a
solution of 14 g of 1,3-dimethyl-1H-pyrazole-4-car-
boxylic acid in 100 ml of water, 4 g of sodium hyd-
roxide was added, and then 16 g of bromine was
added dropwise at room temperature over the course
of 1 h. The reaction mixture was neutralized with 2 N
HCl, extracted with chloroform (3 50 ml), and dried
over MgSO4. The solvent was removed, and the re-
sidue was distilled in a vacuum to obtain 14 g (80%)
1. Darbinyan, E.G. and Matsoyan, S.G., Arm. Khim. Zh.,
1984, vol. 37, no. 3, p. 153.
2. Huttel, R., Wagner, H., and Jochum, P., Justus Liebigs
Ann. Chem., 1955, vol. 593, p. 179.
3. Manaev, A.Yu., Andreva, M.A., Perevalov, V.P., Ste-
panov, B.I., Dubrovskaya, V.A., and Seraya, V.I., Zh.
Obshch. Khim., 1982, vol. 52, no. 11, p. 2592.
of compound VII, bp 45 C (1 mm Hg), n2D0 1.521,
4. Auwers, K.V. and Hollmann, H., Chem. Ber., 1926,
d240 1.5059 [5]. IR spectrum, , cm : 1510 (pyrazole
1
vol. 59, p. 601.
1
ring). H NMR spectrum, , ppm: 2.15 s (3H, 3-CH3),
5. Andreva, M.A., Bolonov, M.I., Isaev, Sh.G., Mu-
shii, R.Ya., Gerevalov, V.P., Seraya, V.I., and Stepa-
nov, B.I., Zh. Obshch. Khim., 1980, vol. 50, no. 9,
p. 2116.
3.81 s (3H, N CH3), 7.51 s (1H, 5-H). Found, %: C
34.38; H 4.31; Br 45.88; N 16.43. C5H7BrN2. Cal-
culated, %: C 34.31; H 4.02; Br 45.65; N 16.00.
6. Antanosyan, S.K., Arm. Khim. Zh., 2004, vol. 59, no. 2,
4-Bromo-1,5-dimethyl-1H-pyrazole (VIII) was
prepared similarly to VII from 14 g of 1,5-dimethyl-
1H-pyrazole-4-carboxylic acid and 16 g of bromine,
yield 12.3 g (70%), bp 52 C (1 mm Hg), n2D0 1.521,
p. 99.
7. Finar, I.L., and Lord, G.H., J. Chem. Soc., 1957, no. 7,
p. 3314.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 2 2007