DE1618177B2 - Process for the preparation of 2,2-dialkyl and 2,2-alkylene glutaric acids - Google Patents

Description

The invention relates to an improved process for the preparation of 2,2-dialkyl and 2,2-alkylene glutaric acids of the general formula I.

R ¹

HOOC-CH ₂ -CH ₂ -C-COOh (I)

R ²

in which R ¹ and R ^{2 are} identical or different alkyl radicals with 1 to 8 carbon atoms, it being possible for these radicals to be linked to form an alkylene radical which forms a 5- to 7-membered cycloalkane ring with the 2-carbon atom of glutaric acid Hydrolysis and oxidation of the corresponding 4-cyano-butyraldehydes of the general formula II

R ¹

NC-CH ₂ -CH ₇ -C-CHO

R ²

From German patent 10 61 309 it is known to produce 2,2-dialkylglutaric acids by adding Acrylic acid on saturated fatty acids which contain a tertiary hydrogen atom in the «position 300 to 350 ° C. However, this process has the disadvantage that the 2,2-dialkylglutaric acids obtained only in very low yields.

It is also known that 2,2-dialkyl-4-cyanobutyraldehydes can be obtained by hydrolysis with mineral acids R ¹

HOOC-CH ₂ -CH ₂ -C-COOh

in which R ¹ and R ^{2 are} identical or different alkyl radicals with 1 to 8 carbon atoms, it being possible for these radicals to be linked to form an alkylene radical which forms a 5- to 7-membered cycloalkane ring with the 2-carbon atom of glutaric acid 4-cyano-butyraldehydes of the general formula II

R ¹

NC-CH ₇ -CH, -C-CHO

R ²

(Π)

by hydrolysis of the cyano group and oxidation of the aldehyde group with oxygen or oxygen-containing Gases in a mineral acidic, water-containing medium are obtained when hydrolyzing and oxidizing at the same time.

The following reaction equation, for example, results for the conversion of 2,2-dimethyl-4-cyanobutyraldehyde:

CH ₃

NC-CH ₂ -CH ₂ -C-CHO

CH ₃

CH,

+ O ₂ , + H ₂ O

- HOOC-CH ₂ -CH ₂ -C-COOh

CH ₃

It was unexpected that the substituted glutaric acids I can be obtained in good to very good yields according to the new process, after how already stated, 2,2-dimethyl-4-cyano-butyraldehyde is only converted into isocaproic acid if it is first hydrolyzed in two operations and then oxidized with atmospheric oxygen. The Ver-

Driving the invention enables the conversion of the 2,2-dialkyl-4-cyanobutyraldehydes into 2,2-dialkylglutaric acids in one process stage and using inexpensive atmospheric oxygen as the oxidizing agent.

The starting materials used in the process of the invention can be obtained by cyanoethylation of dialkyl acetaldehydes with acrylonitrile.

Preferred starting materials II are, for example, 2,2-dimethyl-4-cyano-butyraldehyde, 2-methyl-2-n-propyl-4-cyano-butyraldehyde, 2-methyl-2-n-heptyl - 4 - cyano - butyraldehyde, 1 - (2 - cyanoethyl) - hexahydrobenzaldehyde and 2-ethyl-2-n-butyl-4-cyanobutyraldehyde. The oxidizing agent used is for the new process oxygen or oxygen-containing gases, preferably of the oxygen-containing gases Air. One works at normal pressure or under increased pressure. It is advantageous to turn Press from 15 to 100 at.

As reaction temperatures are generally used temperatures from 0 to 200 ⁰ C, in particular from 20 to 100 ° C.

The reaction of the starting materials is preferably carried out without an organic solvent in aqueous mineral acids that do not oxidize under the reaction conditions, such as hydrochloric acid, phosphoric acid, sulfuric acid or dilute nitric acid, in which, in particular, the starting materials with a low molecular weight are relatively readily soluble. In-turn Ver aqueous mineral acids expedient to work at higher temperatures, for example at 60 to 100 ⁰ C. The resulting, usually less soluble Dialkylglutarsäuren crystallize then generally during cooling largely, thereby enabling easy separation. However, it is also possible to use mixtures of aqueous mineral acids and water-soluble organic solvents such as dioxane, tetrahydrofuran or ketones, which is particularly advisable when reacting starting materials that are sparingly soluble in aqueous mineral acids. When working in mixtures of aqueous mineral acids and organic solvents, if the proportion of the latter is sufficiently large, the reaction products generally remain in solution, while the ammonium salt formed precipitates.

The acid concentration of the aqueous mineral acids and the mixtures of aqueous mineral acids and organic solvent can vary within wide limits. Appropriately, one turns one Acid concentration of at least 5 percent by weight. The upper limit of the scope the acid concentration is generally determined and is determined by the nature of the individual acid For example, for hydrochloric acid it is useful at 35 to 40 percent by weight, for sulfuric acid it is useful at 70 percent by weight. Nitric acid is only used up to a concentration in which it is below The reaction conditions do not yet have an oxidizing effect, which can easily be determined by a preliminary test leaves.

The implementation according to the new process increases depending on the temperature, acid concentration and oxygen pressure generally from 30 minutes to 10 hours.

The process of the invention can be carried out batchwise, for example using a stirred or shaking autoclave. A continuous process can e.g. B. consist in that one the solutions of the starting materials in the aqueous mineral acid with the aid of a metering pump from above in a vertical, filled with ceramic bodies and kept at the reaction temperature Introduces pressure reactor and the compressed with a compressor to reaction pressure and with a Flow regulator dosed oxygen-containing gas passes through in countercurrent.

The substituted glutaric acids I which can be prepared by the process of the invention are valuable Intermediates, e.g. B. for the production of polyesters and pharmaceuticals such as 2,2-dialkylglutarimides, those according to Annali di Chimica, Vol. 56 (1966), pp. 392 to 400, pharmacological action approaching the central nervous system. The parts mentioned in the examples are parts by weight.

example 1

150 parts of 2,2-dimethyl-4-cyano-butyraldehyde are used dissolved in 690 parts of 30% strength hydrochloric acid with cooling and in an autoclave at 70 ° C. for 8 hours shaken under an oxygen pressure of 100 at. When the reaction mixture cools, it crystallizes already a considerable part, the remainder of the 2,2-dimethylglutaric acid formed on concentration. Man washes with ice water and receives 165 parts of 2,2-dimethylglutaric acid, corresponding to a yield of 86% of theory, melting point 80 to 82 ° C (from methylene chloride / petroleum ether).

Example 2

150 parts of 2-methyl-2-n-propyl-4-cyano-butyraldehyde are, as described in Example 1, reacted in 690 parts of 30% strength hydrochloric acid. On cooling, a viscous oil separates out as the upper phase, which slowly crystallizes. This gives 124 parts of 2-methyl-2-n-propyl-glutaric acid, corresponding to a yield of 67% of theory, m.p. 59 to 6I ⁰ C (petroleum ether), boiling point 110 to 112 ° C.

Example 3

150 parts of 1- (2-cyanoethyl) -hexahydrobenzaldehyde are, as described in Example 1, in 785 parts 40% sulfuric acid implemented. The organic deposited after cooling to room temperature Phase crystallizes for the most part and, after washing with cold water, gives 140 parts of 1- (2-carboxylethyl) hexahydrobenzoic acid, corresponding to a yield of 77% of theory, melting point 130 to 132 ° C. (from methylene chloride / petroleum ether).

Claims (1)

Claim: Process for the preparation of 2,2-dialkyl and 2,2-alkylene glutaric acids of the general formula I R ¹ HOOC-CFi ₂ -CH ₂ -C-COOH (1) R ² in which R ¹ and R ^{2 are} identical or different alkyl radicals with 1 to 8 carbon atoms, it being possible for these radicals to be linked to form an alkylene radical which forms a 5- to 7-membered cycloalkane ring with the 2-carbon atom of glutaric acid 4-cyano-butyraldehydes of the general formula II R ¹ NC-CH ₂ -CH ₂ -C-CHO (II) R ² by hydrolysis of the cyano group and oxidation of the aldehyde group with oxygen or oxygen-containing Gases in mineral acid, water-containing medium, characterized in that hydrolyzed and oxidized at the same time. and oxidation with nitric acid to the corresponding ones Can convert 2,2-dialkylglutaric acids (German Patent Specification 8 42 192). However, nitric acid oxidation is very violent and above all difficult to keep under control with larger batches. In the oxidation of dimethylglutaraldehyde acid, which in the first stage by hydrolysis of 2,2-dimethyl-4-cyanobutyraldehyde in mineral acid, aqueous medium, but only isocaproic acid is obtained with atmospheric oxygen and not the expected 2,2-dimethylglutaric acid (Zeitschrift für Naturforschung, Vol. 5b [1950], P. 122). Isocaproic acid instead of 2,2-diinethylglutaric acid according to Angew. Chemie, Vol. 61 (1949), p. 237, also always in the hydrolysis of 2,2-dimethyl-4-cyanobutyric acid, which is derived from 2,2-dimethyl-4-cyanobutyraldehyde can be produced by alkaline oxidation. It has now been found, surprisingly, that 2,2-dialkyl and 2,2-alkylene glutaric acids general formula I.