Russian Journal of Organic Chemistry, Vol. 39, No. 12, 2003, p. 1803. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 12, 2003, p. 1874.
Original Russian Text Copyright
2003 by Zemtsova, Trakhtenberg, Galkina.
SHORT
COMMUNICATIONS
A Procedure for Preparation
of 2-Methylquinoline-4-carboxylic Acids
1
2
1
M. N. Zemtsova , P. L. Trakhtenberg , and M. V. Galkina
1
Samara State Technical University, ul. Molodogvardeiskaya 244, Samara, 443100 Russia
e-mail: ikmoiseev@mail.ru
2
Nayanova Samara Municipal University, Samara, Russia
Received February 28, 2003
2-Methylquinoline-4-carboxylic acids are widely
used in organic synthesis for the preparation of
various derivatives possessing high biological activity
[1 3]. These compounds are usually obtained by the
Pfitzinger reaction, i.e., by heating a mixture of
5-substituted isatin with acetone in the presence of
alkali. For example, 2-methylquinoline-4-carboxylic
acid was synthesized in such a way in 50% yield
[3 5], and 2,6-dimethylquinoline-4-carboxylic acid
was obtained in 60% yield [6]. The yield of 6-bromo-
2-methylquinoline-4-carboxylic acid was only 40%.
Presumably, the low yields of 2-methylquinoline-
4-carboxylic acids prepared by addition of alkali to
a mixture of 5-substituted isatin with acetone is
explained by an appreciable contribution of the side
reaction involving addition of acetone to isatin, which
precedes opening of the isatin ring. The resulting un-
saturated intermediate is likely to undergo tarring at
elevated temperature, thus reducing the yield of the
target product.
yield and minimizing formation of tars, the reactant
ratio and reaction time remaining unchanged.
6-Bromo-2-methylquinoline-4-carboxylic acid
(IIb). A mixture of 8 g (0.035 mol) of 5-bromoisatin
(Ib) with a solution of 16 g (0.28 mol) of potassium
hydroxide in 32 ml of water was stirred for 5 min at
room temperature, 38.23 ml (0.836 mol) of acetone
was added, and the mixture was heated for 8 h under
reflux (on a water bath). The mixture was neutralized
to pH 5 6 with 10% hydrochloric acid, and the pre-
cipitate was filtered off, washed with warm water,
and dried. Yield 12.65 g (93%), mp 259 260 C.
Following a similar procedure, 2-methylquinoline-
4-carboxylic acid (IIa) was synthesized in 91% yield,
mp 238 240 C, and 2,6-dimethylquinoline-4-car-
boxylic acid (IIc) was obtained in 94% yield,
mp 267 268 C. Acids IIa IIc were identified by
the IR spectra and melting points (no depression of
the melting point was observed on mixing with
an authentic sample).
With a view to improve the yield and purity of
6-substituted 2-methylquinoline-4-carboxylic acids
IIa IIc we tried a different order of mixing of the
reactants. According to the proposed procedure,
a mixture of isatin Ia Ic and a 28% solution of alkali
was stirred for 5 min, and acetone was then added.
As a result, we succeeded in increasing the product
REFERENCES
1. Bespalova, Zh.P. and Lipkin, A.E., Khim.-Farm. Zh.,
1970, p. 24.
2. Belen’kaya, R.S., Lipkin, A.E., and Ostryakov, V.M.,
Khim.-Farm. Zh., 1972, p. 13.
3. Ujiie, T., Chem. Pharm. Bull., 1966, vol. 14, p. 461.
4. Robinson, E.A. and Bogert, M.T., J. Org. Chem.,
1936, p. 65.
5. Sarkis, G.Y., J. Chem. Eng. Data, 1972, vol. 17,
p. 388.
6. Palmer, M.H. and McIntyre, P.S., J. Chem. Soc. B,
R = H (a), Br (b), Me (c).
1969, p. 539.
1070-4280/03/3912-1803$25.00 2003 MAIK Nauka/Interperiodica