DE638821C - Process for the preparation of ª ‡ - (ª † '-Pyridyl) -alkylcarboxylic acid esters - Google Patents

Description

According to patent specification 459 903, 5, 5-dialkylbarbituric acids are obtained by heating in weakly alkaline solution ureals of dialkyl acetic acids.

It has now been found that 5- (γ-pyridyl) -S-alkylbarbituric acids give two types of fission products with the same treatment, one of which, like the ureides, is insoluble in alkalis, the other is soluble. Is working in a strongly alkaline solution, only the alkali-soluble cleavage products are obtained. The latter have now proven to be salts of a- (y'-pyridyl) -alkylcarboxylic acids, from which the free acids and their esters are represented by known methods permit.

It was further found that the alkali-insoluble cleavage products by further hydrolysis, which takes place in this case by dilute mineral acids, pass into the a- (y'-pyrid \ i) alkylcarboxylic.

example 1

200 parts of s- (y-pyridyl) -5-äthylbarbituräure become in 2000 parts by volume of water with the addition of as much ammonia as is necessary to achieve a solution, dissolved and after adding another 500 parts

Ammonium carbonate heated on a water bath for 5 hours. Crystallize on cooling 59 parts of alkali-insoluble cleavage product. After being separated from the latter from the filtrate, after acidification with acetic acid, 57 parts of unchanged barbitufic acid regained. The weakly acidic filtrate of the same is exhausted with copper sulfate solution precipitated, whereby 66 parts of a light blue copper salt are obtained.

The 59 parts of alkali-insoluble cleavage product obtained in the above cleavage are in 300 parts by volume of 10% hydrochloric acid dissolved and boiled for ι hour on the re-nut cooler. After neutralizing with sodium carbonate, the solution is adjusted to be weakly acidic and then precipitated exhaustively with copper sulfate solution. So there are another 54 parts of the light blue copper salt.

The total amount of the copper salt thus obtained is then boiled in 1000 Raumteileri absolute alcohol after the addition of iioTei- ^ ⁰ len anhydrous copper sulfate and 75 parts by volume concentrated sulfuric acid on the reflux condenser for 5 hours, filtered hot and the alcohol largely distilled off in vacuo. The residue is taken up with water and, while cooling, with am-

*) The patent seeker indicated the following as the inventors:

Dr. Curt Räth in Radebeul, Dr. Rudolf Gebauer in Dresden and Dipl.-Ing. Dr. Heins Falta in Berlin.

made moniak alkaline. The - (/ -Pyridyl) -butyric acid ethyl ester separated as oil

C ₂ H ₅ -CH-COOC ₃ H ₅

is absorbed with ether. After distilling off the ether, the ester is obtained with a boiling point of ₁₂ 130 to 135 ° in a yield of 80 ° / ₀ of theory, taking into account the recovered starting material.

If the copper salt described above is broken down in an aqueous suspension with hydrogen sulfide, the free a- (/ -pyridyl) -butyric acid is obtained in prisms ^{after the copper sulfide has been separated off by evaporation of the filtrate at room temperature, which melts at ao 89 0} with decomposition. During storage, the acid gradually splits off carbonic acid with the formation of γ-propylpyridine.

Example 2

20 parts of 5- (γ-pyridyl) -S-ethylbarbituric acid are 2ovolumprozentiger in 100 parts by volume Sodium hydroxide solution heated on the water bath for 1 hour and the resulting solution to Dry evaporates. The salt mixture obtained in this way has an absolute value of 200 parts by volume Alcohol and 200 parts by volume of 30 percent by volume alcoholic hydrochloric acid 3 hours am Reflux condenser boiled. After cooling, it is diluted with 100 parts by volume of water, stirred with sodium carbonate until an alkaline reaction and filtered off with suction. From the filtrate the alcohol is driven off by vacuum distillation on a water bath and the residue is extracted with ether after cooling.

After distilling off the ether and distillation of the residue in vacuo, the α- (/ -pyridyl) -buttersäureäthylester is obtained in a yield of 80 to 90 ° / ₀ of theory.

Example 3

If the 5- (γ-pyridyl) -5-ethylbarbituric acid is replaced in Example 2 by 5 - (/ - pyridyl) -5-methylbarbituric acid and leads the alkaline Cleavage in the same way as described there, one wins in the esterification the a - (/ - pyridyl) propionic acid ethyl ester of the dry sodium salts in equally good yield, which at 22 mm has a boiling point of 145 to 148 °.

From the aqueous solution of the sodium salts, after acidification with acetic acid, by adding copper sulfate solution, copper can be precipitated, from which a solution of a- (/ -Pyridyl) -propionic acid is obtained, which, brought to dryness at a moderate temperature, leaves the pure acid in white crystals. The latter melt at about 90 ⁰ under carbon dioxide development, remains after the end of pure y-ethylpyridine.

Example 4

ι Part 5- (γ-pyridyl) -5-n-butylbarbituric acid is heated in 2 parts by volume 2ovolumprozentiger sodium hydroxide solution ι hour on the water bath and the resulting solution evaporated to dryness. The resulting salt mixture is boiled with 7.5 parts by volume of 15 percent by volume alcoholic hydrochloric acid in a reflux condenser for 3 hours. In the work-up carried out according to Example -2 , the a- (/ -Pyridyl) -n-caproic acid ethyl ester, which boils under 13 mm pressure at 148 to 150 °.

Example 5

If you start with 5- (y-pyridyl) -S-isopropylbarbituric acid and if the cleavage and esterification are carried out in the same way as described in Example 4, one arrives at the ethyl cc - (/ - pyridyl) isovaleric acid boiling at 240 °.

The in some of the above examples to characterize the a - (/ - pyridyl) -alkylcarboxylic acids The cited cleavage into alkylpyridines is the subject of another patent and is therefore not claimed here.

Claims (2)

Patent claims: 1. A process for the preparation of a- (/ -pyridyl) -alkylcarboxylic acid esters, characterized in that 5- (y-pyridyl) -5-alkylbarbituric acids are treated in the heat with alkaline agents and the α- (γ '- pyridyl) -alkylcarboxylic acid salts converted into the esters in a manner known per se. 2. The method according to claim 1, characterized in that in the alkaline Treatment of any alkali-insoluble intermediate products obtained by heating with dilute mineral acids in a - (/ - pyridyl) -alkylcarboxylic acids and the latter via their salts in per se known Way converted into the ester.