Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-06-23
2001-03-27
Kight, John (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06207833
ABSTRACT:
The invention relates to a method for preparing (2-quinolylthio)acetic acid.
(2-quinolylthio)acetic acid and 2-(quinolylthio)acetic acid hydrochloride are important intermediates for the preparation of stabilizers in photothermographic materials, which are disclosed for example in EP 0 631 176.
Methods for the production of 2-(quinolylthio)acetic acid are known in prior art.
For example G. F. Duffin, J. D. Kendall, J.Chem.Soc, 1951, pp. 734 ff disclose a process for the preparation of 2-(quinolylthio)acetic acid by reacting quinoline-2-thiol with thioacetic acid. Quinoline-2-thiol is obtained by reacting 2-chloroquinoline with thiourea.
The present invention provides a single stage method for the production of 2-(quinolylthio)acetic acid by reacting 2-chloroquinoline with mercaptoacetic acid; the desired 2-(quinolylthio)acetic acid is obtained with high purity and yield.
Therefore the object of the invention is a method for the production of 2-(quinolylthio)acetic acid of formula I
and its salts, comprising reacting 2-chloroquinoline of formula II
with mercaptoacetic acid in aqueous medium and, if desired, converting the resulting salt into the free acid or the resulting acid into its salt.
The method of the invention provides high yields and high purity which is necessary for the use of the product for example in the process described in EP 0 631 176.
2-chloroquinoline is melted and further reacted with mercaptoacetic acid in aqueous medium. The reaction mixture is heated, cooled and the product I is precipitated.
The reaction may be carried out in alkaline or acidic medium.
At first 2-chloroquinoline is melted at a temperature of about 60 to 70° C.
If the reaction is carried out in an alkaline medium an inorganic base, for example NaOH, KOH etc. and if desired tetrabutylammoniumiodide as phase-transfer catalyst is added.
Then mercaptoacetic acid is added, if desired in aqueous alkaline solution. The reaction mixture is heated to reflux temperature. After the reaction is finished the reaction mixture is cooled to room temperature and further, if desired, washed with an inert organic solvent, such as ethers, like t-butylmethylether, or ethylacetate or toluene or benzene etc. The aqueous phase is then acidified by adding an inorganic acid, such as HCl, the product is precipitated as its hydrochloride. Precipitation is done in acidic medium at a pH of about <1. The resulting precipitate is washed, for example with distilled water and dried.
The reaction may be carried out at low temperatures. The melted 2-chloroquinoline is taken up in aqueous medium, e.g. distilled water, and mercaptoacetic acid is added at a temperature of 35 to 65° C., preferably 45-50° C. After the reaction is finished, the reaction mixture is cooled, preferably to a temperature of 40-60° C. and the pH of the reaction mixture is adjusted to 8-11, preferably to 9-10 by adding a base, for example NaOH, KOH or the like. Then the reaction mixture is cooled to room temperature. Washing and precipitation is done as indicated above.
If 2-(quinolylthio)acetic acid is obtained by adding HCl in the form of its hydrochloride, the free acid may be isolated by solving the hydrochloride for example in an aqueous solution of sodiumhydrogencarbonate or sodiumcarbonate or the like, follwed by further precipitation in acidic medium, for example at a pH of about 3-4.
If the reaction is carried out in acidic medium, the molten 2-chloroquinoline is taken up in an aqueous medium, for example distilled water and an inorganic acid, for example HCl conc. is added. Further mercaptoacetic acid is added and the reaction mixture is heated to a temperature of 45° C. to reflux temperature of the reaction mixture. After the reaction is finished, the reaction mixture is cooled to room temperature to 0° C. and if desired is diluted with an inert water mixable solvent, for example acetone.
Further the pH may be adjusted to about 8-11, preferably 9-10 by adding an inorganic base; isolation of the free acid is done as indicated above.
Reaction time is dependant on the reaction temperature and is usually about 10 min to 24 h, preferably 30 min to 12 h. The reaction is monitored by conventional methods like thin layer chromatography and the like.
The hydrochloride obtained by the above mentioned method as well as the free acid obtained by the above mentioned method may be used as intermediate in the process described in EP 0 631 176. In this case the sodium salt of 2-(quinolyl)thio-acetic acid is formed by adding two equivalents of the appropriate base, for example sodiumhydroxide. Further process steps are described in EP-0 631 176.
The sodium salt of 2-(quinolylthio)acetic acid is reacted with bromine and sodiumhydroxide at a temperature below 30° C., the precipitate is siphoned and dried. If desired the precipitate is recrystallized.
REFERENCES:
patent: 5658751 (1997-08-01), Koller et al.
patent: 0631176 (1994-12-01), None
Duffin et al., “Anhydro-compounds from Nitrogen-containing Derivatives of Thioglycollic Acid. Part 1. Pyridine and Quinoline Compounds.”, J. Chem. Soc, 1951, pp. 734-739.
Kight John
Loba Feinchemie AG
Robinson Binta
Wenderoth , Lind & Ponack, L.L.P.
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