DE1768114A1 - Process for the production of alpha-ketoglutaric acid - Google Patents

Description

PAINT FACTORY _{BAYERAG 17681n} LEVERKUSEN-Beyerwerk FAfENT-A (TElLUNC

O APR 1. ₁₉₆₈ Process for the production of ^ -ketoglutaric acid

The present invention relates to a new,

elegant method of making Of -Keto- '^ glutaric acid, which is used as an intermediate for the

Extraction of valuable pesticides, especially

on phosphoric acid ester ijasis can be used.

From "Organic Syntheses", anthology III (1955) »page 510 it is already known to produce o (-Ketoglutaric acid by condensation of succinic acid diethyl ^ ster with oxalic acid diethyl ester and subsequent acid hydrolysis and decarboxylation of the initially formed * Ot-ketotricarboxylic acid triethyleter.

Furthermore, in "Journal of the chemical society", Vol. 119 (1921), pages 326, 2014- and 2019 the production of ^ -Ketoglutaric acid by hydrolysis of d , ot'-dibromoglutaric acid ethyl ester, 0 (, ß-Dibromglutaric acid or . & -3romglutaric acid ethyl ether described.

However, all known methods have serious disadvantages.

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In the method according to "Organic Syntheses" (loc.cit.), For example, one has to work in the presence of potassium alcoholate as a condensation agent in order to achieve good yields. In addition, due to the necessary decarboxylation of the succinic acid ester to be used as the starting material, only about half of it is converted to ketoglutaric acid. Finally, it is necessary to carry out the reaction in an absolutely anhydrous medium. Jb ¹ This laboratory procedure is therefore not suitable for carrying out on an industrial scale.

The other methods mentioned above have at all no practical relevance, since the starting substances required for this are very difficult to access, the ketoglutaric acid, besides hydroxyglutaric, cyclopropanecarboxylic and unsaturated carboxylic acids, only ale By-product is obtained and can hardly be separated from these.

It has now been found that (! (- ketoglutaric acid in a technically simple manner with very good yields and in excellent purity is obtained if <f, <f dichloro-glutaric acid alkali or brodalkali salts in aqueous solution or suspension with salts aua weak acids and strong bases at elevated temperature. The smooth and uniform course of the process according to the invention is completely surprising. Br could cannot be foreseen in any way, because it is known that the hydrolysis of haloglutaric acids,

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eg 0 (-Bromo- as well as öt, ß- or of, <k * -Dibromoglutaric acid leads to a multitude of different products which are difficult to separate (see "Journal of the Chemical Society", loc.cit.).

If one uses ° (, 0 (-dichloroglutarate8 sodium and Sodium benzoate as starting materials, so the procedural reaction by the following flow chart be reproduced:

^ COONa ^ COONa

CH ₂ CH ₂

CH ₂ + 2C ₆ H ₅ COOHa + H ₂ O »CH ₂ + 2HaCl + 20 _β Η ^ 3 00Η

ι ι

C-Cl " _Q

COOHa ^C00Na

The al β Auegangesubstanz required Q ', (Ä-Dichlorglutaric acid is today also in technical quantities by accumulation from dichloroacetic acid ester to acrylic acid ester easily accessible (cf. German Patent 1,134,984 and "Zeitschrift für Angewandte Chemie", Vol. 72 (1960), p. 1001).

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Of all the second output components to be used. Salts of weak acids and strong bases, organic and inorganic in nature, can be used. The alkali metal or ammonium salts are preferably used. For example: Sodium and aluminum formate, acetate, propionate and benzoate.

Furthermore, alkali carbonates, bicarbonates, borates, phosphates or alkali metal have also been used for the stated purpose -hydrogen phosphate proven.

As already mentioned above, the process according to the implementation in an aqueous medium and at elevated temperature, preferably carried out at the boiling point of the aqueous solution or suspension.

As is apparent from the above Keaktionsschema, reacting 2 moles of de · per mole ° (, Ot-dichlorglutarsauren salt is about respective salt of weak acid and strong base. An excess of the latter, although harmless, but does not result in increasing the yield of ^ ketoglutaric acid.

Furthermore, it has been found to be expedient to continue stirring the reaction mixture for a longer time (24 to 72 hours) after the starting components have been combined to complete the reaction. In this case, the process product is obtained in particularly good yield and purity.

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The reaction mixture is worked up in Usually by separating off the by-products (auxiliary acid and alkali metal chloride) and evaporation the solution. The 0f-ketoglutaric acid remaining in the residue is ready for most uses pure enough. If necessary or desired, however, "it can easily be further" purified by dissolving the crude product in warm ethyl acetate with the addition of animal charcoal and re-trapping with petroleum ether.

According to a special embodiment dee claimed The process does not start with the free (X, cC-dichloroglutaric acid or its alkali or alkaline earth salts from, but saponified the corresponding dialkyl, preferably dimethyl or ethyl esters as they are according to the German Patent 1,134,984 obtained first in aqueous solution with alkalis and continues the Saponification products onnt in a "one-pot" process Intermediate isolation or cleaning afterwards immediately continue ura with the relevant salts from weak acids and strong bases.

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The advantages over the method according to the invention the state of the art are clearly evident. Above all, they consist in the easy accessibility of the ale Starting material required (X, 0-dichiorglutaric acid eowie the auxiliary substances, furthermore in the smooth, single-stage course of the implementation.

Pie Oi-ketoglutaric acid is - as already mentioned - a Valuable intermediate product for the production of pesticides, in which they are mainly through phosphorylation can be transferred. The product also serves as a starting material for the synthesis of certain heterocyclic compounds Compounds which are also used as pesticides.

The following examples explain the invention in more detail: Example 1;

dissolves 667 g of dto-dichloro-dichloro-glutaric acid with a melting point of 103 ° C. (prepared by acid hydrolysis of the corresponding dimethyl or ethyl ester) in 5 l of water and neutralizes the solution with external cooling with 200 g of sodium hydroxide in 1.25 l of water. After the addition of 725 g of sodium benzoate, the reaction mixture is heated to extinction for 48 hours, then cooled to normal temperature and the evaporated benzoic acid is filtered off with suction. Bas Piltrats afciert, add mn bit of hydrochloric acid until it tinen p ^ value of? '»Ο? ^ Tst. Bi ^ here

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Reprecipitating benzoic acid is again separated off. Subsequently, the pItrate is evaporated to dryness. For the purpose of separating off the sodium chloride formed as a further by-product, the residue is triturated with 4 liters of acetone. The undissolved parts are sucked off. Finally the acetone solution is evaporated to dryness. The residue left behind is 325 g (89 liters of theory) of OC-ketoglutaric acid, which ^{melts at 108 to 111 °} C. and is pure enough for most reactions. For the purpose of further purification, the crude product can be dissolved in 2.5 l of warm ethyl acetate. Animal charcoal is added to the solution, the mixture is filtered and the pure (^ -ketoglutaric acid is precipitated from the filtrate after cooling to room temperature by adding 2.5 liters of petroleum ether. In this way, 300 g (81 parts of theory) of a product with a melting point are obtained 113 ⁰ C. If equivalent amounts of sodium acetate or hydrogen carbonate are used instead of sodium benzoate under the same conditions, similarly good results can be achieved

Example 2:

A solution of 229 g (1 Hol) ÖCcC-Bichlorgluiarsäuredimethylester in 1 l of water is added dropwise with stirring and intensive external cooling within about 4 hours with 80 g hatriuene hydroxide - dissolved in 1.5 1 water -

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added and the reaction mixture was subsequently stirred at room temperature. The solution obtained is then clear and reacts neutrally. 300 g of sodium benzoate are added to the mixture. Thereafter, it is * cooled for 48 hours boiling efhitSt to room temperature, * share of the unsolved .gebliebenen An removed by suction, the filtrate is acidified with koneentrierter hydrochloric acid, the precipitated benzoic acid in turn drawn off and the aqueous mother liquor at a low temperature (about 40 ⁰ C ) on the Rotationeverdaiipfer to dryness. The resulting sodium chloride is removed as described in Example 1 with acetone and finally the solvent is evaporated. The residue that remains solidifies in crystalline form. The thus obtained <sC-Ketoglutareäure melts at 109 to 111 ⁰ C. The yield is 115 g (84 $> of theory).

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Claims (6)

Patent claims: 1) Process for the production of ol-ketoglutaric acid, characterized in that manoi, o (-dichloroglutaric acid Alkali or alkaline earth salts in aqueous solution or suspension with salts from weak acids and strong bases at elevated temperature. 2) Method according to claim 1, characterized in that that one works at the boiling point of the reaction mixture 3) Process according to claim 1 and 2, characterized in that about 2 moles of the salt in question of weak acid and strong base are used per mole of the Oi, oC-dichloro-glutaric acid salt. 4) Method according to claim 1 to 3, characterized in that that the output θ substance o (, o (-di chi orglut ar saures Sodium used. 5) Process according to claim 1 to 4, characterized in that the salts of weak acids and strong bases are used Alkali or ammonium salts of formic, acetic, propionic or benzoic acid or alkali carbonates, hydrogen carbonates, -borates, -phosphates or -hydrogenphosphates are used. Le A 11 398 - 9 - 109841/1873 . 17681H 6) Process according to claim 1 to 5, characterized in that one oC, £ \ -Dichlorglutaraäure-dialkyleater, preferably .dimethyl- or -äthyleater saponified in aqueous solution with Allalien and the resulting saponification unaproducts without intermediate isolation or purification then nit the relevant salts from weak acids and strong bases. Le A 11 398 - 10 - 109841/1873