DE1768582B - Process for the preparation of 2,3-dichloro-4-butyryl-phenoxyessigsäurebzw. their ammonium salts - Google Patents

Description

in which R ₁ , R ₂ and R ₃ are independently hydrogen atoms or alkyl groups having 1 to 5 carbon atoms or R _{1 is} a hydrogen atom and R ₂ and R ₃ together with the NH group are a piperidino or morpholino radical, by Friedel-Crafts acylation with n-butyryl chloride in the presence of aluminum chloride, characterized in that methyl or ethyl 2,3-dichloro-phenoxyacetate is subjected to Friedel-Crafts acylation with n-butyryl chloride, the complex obtained is heated until the evolution of hydrochloric acid ceases and the reaction mixture is treated with decomposed a mineral acid, separates the formed 2,3-dichloro-4-butyryl-phenoxyacetic acid methyl or ethyl ester from the reaction mixture and in a known manner either. phenoxyacetic acid of a high degree of purity or its ammonium salts of the general formula I my

H ₃ C-CH ₂ -CH ₂ -CO- ^ ^- VO-CH ₂ -COONHR ₁ R ₂ R ₃

(D

Cl

Cl

in which R ₁ , R ₂ and R ₃ are independently hydrogen atoms or alkyl groups having 1 to 5 carbon atoms or R _{1 is} a hydrogen atom and R ₂ and R ₃ together with the NH group are a piperidino or morpholino radical.

Among the rather sparse literature references relating to Friedel-Crafts reactions of phenoxyacetic acids the note is remarkable that the chloroacetylation of phenoxyacetic acid and Phenylacetic acid and, even more easily, the chloroacetylation of the esters of phenylacetic acid in carbon disulfide going on (Ber. d. dtsch. Chem. Ges., Vol. 38 [1905], p. 2609). The Production of various phenoxyacetic acid derivatives by Friedel-Crafts reaction only ever the free carboxylic acid is used as a starting material (J. Med. Pharm. Chem., Vol. 5 [1962], p. 660). So was z. B. 2,3-dichloro-4-butyryl-phenoxyacetic acid from 2,3-dichloro-phenoxyacetic acid and butyryl chloride manufactured. In this way, the crude reaction product turned out to be a 77% yield obtained mixture consisting of several substances, from which by 6 to 7 times recrystallization (repeated from benzene and cyclohexane, then from methylcyclohexane, from a mixture of acetic acid and water and finally from methylcyclohexane) the keto acid assumed to be pure from F. 110 to lirC could be obtained (USA.Patent 3,255,241, Example 15A; Belgian patent specification 640 050, example IIIA). After the Repeatedly carefully reworked attempts by the applicant could at most with this product Yields of about 35% and of fairly dubious purity can be obtained since the resulting Reaction product in addition to the 4-butyryl derivative considerable Contains amounts of the 6-butyryl derivative and other by-products. In this synthesis as 2,3-Dichloro-phenoxyacetic acid used as the starting material is a known compound (Botan. Gaz. 112. 250, 1951; Chemical Abstracts, 45, 7055, 1951).

Because of the disadvantageous feasibility of carrying out the above-mentioned Friedel-Crafts reaction with 2,3-dichloro phenoxyacetic acid, another route has already been taken for the synthesis of the butyryl derivative Here, 2,3-dichlorophenol is used as the starting material, and the desired product is in five Reaction steps obtained: the 2,3-dichlorophenol is first converted into 2,3-dichloroanisole, from This becomes 2,3-dichloro-4-butyryl-anisole by Friedel-Crafts reaction produced, which then by ether cleavage in the presence of aluminum chloride is converted into 2,3-dichloro-4-hydroxy-butyrophenone. The pheriolic hydroxyl group of the latter Compound is alkylated with ethyl bromoacetate, and finally the is obtained 2,3 - dichloro - 4 - butyry 1 - phenoxyacetic acid ethyl ester saponified with alcoholic potassium hydroxide solution (USA.-Patent 3 255 241, Examples 138A to C; Dutch dische Auslegeschrift 6 501 968, Examples IUA to III C). Similarly, but from recrystallized tem ethyl ester and carried out with more careful saponification, this compound was after the Be play IA to ID of the Belgian patent specification 654 486 or according to the examples IHA to IHC of the down Rural interpretation document 6 415 013 produced. Besides the awkwardness, this procedure has also the further disadvantage that immediately or after a single recrystallization only a crude

Product is obtained from the mp 100 to IO3 ° C, from which the desired, assumed to be pure, melting connection at 110 to! ITC only through further wasteful cleaning operations can be obtained.

We have now surprisingly found that the butyrylating of the aromatic nucleus of 2,3-dichlorophenoxyacetic acid in the 4-position by Friedel-Crafts reaction runs almost quantitatively and

H ₃ C-CH ₂ -CH ₂ -CO

in which R ₁ , R ₂ and R ₃ are independently hydrogen atoms or alkyl groups having 1 to 5 carbon atoms or R] is a hydrogen atom and R ₂ and R ₃ together with the NH group are a piperidino or morpholino radical, by Friedel-Crafts acylation with n-butyryl chloride in the presence of aluminum chloride, which is characterized in that 2,3-dichloro-phenoxyacetic acid methyl or ethyl ester is subjected to Friedel-Crafts acylation with n-butyryl chloride, the complex obtained is heated until the evolution of hydrochloric acid ceases .Reaction mixture decomposed by treatment with a mineral acid, separates the formed 2,3-dichloro-4-butyryl-phenoxyacetic acid methyl or ethyl ester from the reaction mixture and in a known manner either by acid hydrolysis into the free 2,3-dichloro 4-butyryl-phenoxyacetic acid and this optionally converted into the ammonium salt of the general formula I odei the 2,3-dichloro-4-butyryl-phenoxyacetic acid methyl or ethy The ester is converted into the corresponding ammonium salt of the general formula I in a manner known per se and this optionally converted into the free acid.

When carrying out the process according to the invention, the methyl or ethyl 2,3-dichlorophenoxyacetate is reacted with aluminum chloride and butyryl chloride at temperatures below 50 ° C. without solvents or in the presence of solvents to form the Friedel-Crafts complex. In the case of the use of solvents may be advantageous in carbon disulfide at temperatures between -5 and +5 ⁰ C be used. If the complex formation is carried out at low temperatures using carbon disulfide as the solvent, the mixture is then slowly heated to the boiling point of the solvent, the reaction mixture gradually turning a heli-violet color. If a complex is formed in the absence of solvents, the reaction mixture shows a dark purple color. The aluminum chloride complex prepared in the above manner is then kept at 35 to 55 ° C. until the formation of hydrogen chloride has ceased; then the complex is decomposed by adding concentrated hydrochloric acid (or another mineral acid) and the methyl or ethyl 2,3-dichloro-4-butyryl-phenoxyacetate obtained as an intermediate is isolated. The ester obtained in this way is then either directly decomposed by acid hydrolysis into the free 2,3-dichloro-4-butyrylphenoxyacetic acid, which can then optionally be converted into the desired ammonium or amine salt, or the ester is also fractionated by vacuum Purified 4-butyryl derivative can be obtained with 85 to 90% yields if the starting material used is methyl or ethyl 2,3-dichlorophenoxyacetate in place of 2,3-dichlorophenoxyacetic acid. Accordingly, the invention relates to a process for the preparation of 2,3-dichloro-4-butyryl-phenoxyacetic acid or its ammonium salts of the general formula I

0-CH ₂ -COO-NHR ₁ R ₂ R ₃

Reacting with ammonia or with an amine of the general formula NR ₁ R ₂ R ₃ , in which R ₁ , R ₂ and R _{3 have} the above meaning, converted directly into the corresponding ammonium salt of the general formula I, from which the 2, 3-dichloro-4-butyryl-phenoxyacetic acid can also be released.

For the preparation of the salts of the general formula I, as amines of the general formula NR ₁ R ₂ R _{3, in} addition to ammonia, z. B. butylamine, diethylamine, piperidine or morpholine can be used; the reaction of the esters with these amines is advantageously carried out in an aqueous-alcoholic medium.

Methyl and ethyl 2,3-dichlorophenoxyacetates are new compounds that have not been described in the literature. These starting materials for the process according to the invention are prepared by reacting a 2,3-dichlorophenol alkali salt with a methyl or ethyl monohaloacetate or esterifying 2,3-dichlorophenoxyacetic acid with catalytic amounts of a mineral acid with methanol or ethanol.
The esters of 2,3-dichloro-4-butyrylphenoxyacetic acid obtained with excellent yields as an intermediate product by the process according to the invention have a significantly more uniform melting point than that which is the only ester prepared in a laborious manner using the method of US Pat. No. 3,255,241 Ethyl 2,3-dichloro-4-butyryl-phenoxyacetate. This fact can be explained by the fact that in the process according to the invention the acylation of the aromatic nucleus takes place almost exclusively in the 4-position and the 6-butyryl by-product is only formed in very insignificant amounts. These insignificant amounts of the by-product can be removed from the keto esters purified by vacuum fractionation in a simple manner, by a single recrystallization from lower alcohols or from mixtures of ether and petroleum ether or of benzene and petrol without significant losses.

The 2,3-dichloro-4-butyryl-phenoxyacetic acid obtainable by the hydrolysis of these keto esters shows after recrystallization from benzene a melting point of 114 to 115 ° C. By hydrolysis of the invention Ketoester intermediates produced can also be used without further purification free keto acid with a melting point of 110 to 112 ° C can be obtained. The hydrolysis of the ketoesters is surprising Way when heated in dilute aqueous mineral acids, e.g. B. in 5 to 10% hydrochloric acid almost quantitative.

Particularly advantageously, these products can be prepared by the formation of the ammonium salts of the general formula I, purified, In this way one can also be made in any desired manner produced and at 100-112 ⁰ C melting 2,3-dichloro-4-butyryl-phenoxyacetic acid - wherein it is not about a dimorphic modification as it has sometimes been assumed, but in all cases contaminated products - a pure tarsächlich be obtained at 114 to 115 ⁰ C melting product.

The keto compounds which can be prepared according to the invention are valuable intermediate products for preparation of diuretic drugs.

The process according to the invention is illustrated in more detail by the examples below.

example 1
Manufacture of the starting product

20th

800 ml of methanol are introduced into a 4 liter round bottom flask equipped with a reflux condenser, stirrer and water bath, and 56.7 g (2.47 g atom) of comminuted sodium metal are added over the course of one hour while stirring. During the addition, the reaction mixture heats up to the boiling point of the methanol. After complete dissolution of the sodium, the mixture was cooled to 2O ⁰ C and mixed in 30 minutes with a solution of 400 g (2.46 mol) of 2,3-dichlorophenol in 400 ml of methanol. 268 g (2.47 mol) of methyl monochloroacetate were then added to this mixture at 20 ° C. in the course of 5 minutes. The reaction mixture was left to stand for 1 hour, then the temperature of the water bath was increased to 85 ° C. over 2 hours. The mixture was then refluxed for a further 4 hours, then the precipitated sodium chloride was removed by filtering the still hot reaction mixture and washed with 50 ml of methanol heated ^{to 60 to 65 ° C. each time.} The combined methanolic filtrate was cooled to -5 ° C., left to stand at this temperature for 1 hour, and then the methyl 2,3-dichlorophenoxyacetate which separated out in the form of snow-white, shiny needle-shaped crystals was filtered off. The crystals obtained were suspended in 400 ml of water and filtered again with strong suction, washed twice with 200 ml of methanol each time at 0 ° C. and dried. Yield 400 to 445 g (69.5 to 77% of theory), F. 92 to 93 ^° C.

Analysis: C ₉ H ₈ Cl ₂ O ₃ .

Calculated ... C 45.98, H 3.43, Cl 30.17%;
found .... C 46.07, H 3.65, Cl 30.20%.

55

60

The methanolic mother liquor was concentrated to half its volume and cooled, the precipitated Product filtered off and recrystallized from methanol; in this way another 55 to 80 g pure ester obtained. .

The pure product melts after repeated recrystallization at 93.8 ⁰ C. Solubility in methanol at 20 ° C 2.5 g / 100 ml; at 65 ^° C. 33 g / 100 ml.

Implementation according to the invention

568 g (4.26 mol) of anhydrous aluminum chloride and then 400 ml (510 g) of anhydrous carbon disulfide were introduced into a four-necked round bottom flask with a volume of 21 volume and equipped with a reflux condenser equipped with a thermometer, dropping funnel and calcium chloride tube Mixture was cooled and the suspension was stirred until it had cooled to -5 ° C. 227 g (213 mol) of butyryl chloride were then added dropwise at such a rate that the internal temperature of the reaction mixture remained ^{below 0 ° C. during the addition.} This addition took 30 to 40 minutes, then the reaction mixture was also stirred for a ^{further between -5 and 0 °} C. for 30 minutes and then 250 g (1.06 mol) of methyl 2,3-dichlorophenoxyacetate were added in small portions, care being taken that the temperature did not exceed the limits given above. This addition took about 20 to 30 minutes to complete.

Then the cooling bath was removed and replaced with a 15-20 ° C water bath and temperature this water bath was increased to 55 ° C. within one hour. Upon reaching this Temperature, the reaction mixture began to boil and its originally yellow color changed in purple. The refluxing was continued for 3.5 hours; during this time the The reaction was practically complete and the evolution of hydrochloric acid ceased. That way The reaction mixture obtained was then concentrated on a mixture of 4.5 kg of crushed ice and 500 g. Poured hydrochloric acid. The desired keto ester was in the lower yellowish, oily phase, in carbon disulfide solved, received; the aqueous phase was decanted and the oily phase by repeated Adding and decanting water washed thoroughly.

The decanted aqueous phases were combined in a large separating funnel with 1300 ml of benzene shaken out, then the aqueous phase was removed and that obtained in the above manner in carbon disulfide dissolved ketoesters added to the benzene phase. After shaking together, the aqueous Phase removed, the benzene phase washed with 3 l of tap water, then with 2 l of distilled water and dried over 100 g of anhydrous sodium chloride. After the carbon disulfide and benzene had been distilled off, 316 g of crude 2,3-dichloro-4-butyryl-phenoxyacetic acid methyl ester (97.5% the theory).

The crude product was fractionated in vacuo; below 2 Torr distilled first at 150 to 160 ° C of the unreacted methyl dichlorophenoxyacetate (mostly just a few drops), and then goes to 210 up to 215 ° C the desired product. To this 280 to 290 g of methyl 2,3-dichloro-4-butyrylphenoxyacetate (86 to 89.5% of the Theory) in the form of a light yellow oil.

For further purification, this product was added to the mixture of 140 ml of benzene and 1120 ml of gasoline dissolved hot, and then the solution was cooled to -5 ° C. That initially excreted in an oily form Product solidified in 4 to 5 minutes to a white crystal mass, which is filtered off and with a - 5 ° C cooled mixture from 30 m! Benzene and

240 ml of gasoline was washed. In this way, 260 to 270 g of pure methyl 2,3-dichloro-4-butyrylphenoxyacetate were obtained (80 to 83 of theory) obtained, m.p. 44 to 46 ° C.

Analysis: C ₁₃ H ₁₄ Cl ₂ O ₄ .

Calculated ... C 51.16, H 4.62, Cl 23.24%;
found .... C 51.30, H 4.73, Cl 23.18%.

The product obtainable by further purification operations, and crystallized from methanol pure product melting at 49 to 5O ⁰ C; Kp _n-9 210 to 212 ° C.

3.05 g (0.01 mol) of the methyl 2,3-dichloro-4-butyryl-phenoxyacetate obtained in the above manner were dissolved in 10 ml of ethanol, the solution with 2 ml of conc. Ammonium hydroxide solution is added and the mixture is left to stand for 20 hours at room temperature. The ammonium salt began to be excreted while standing; the mixture was then held at 40 to 45 ° C. for an additional 5 hours to complete the reaction. After the addition of 5 ml of benzene, 10 ml of the solvent mixture were distilled off. The residue was kept for several hours at 0 ^° C., the separated ammonium salt was filtered off and washed twice with 2 ml of ice-cold ethanol each time. In this way, 2.65 g of crystalline 2,3-dichloro-4-butyryl-phenoxyacetic acid ammonium salt were obtained; M.p. 195 to 197 ° C (decomposition). By concentrating the mother liquor further, 0.15 g of this product could still be obtained.

Analysis: C ₁₂ H ₁₅ Cl ₂ NO ₄ .

Calculated ... N 4.55, Cl 23.01%;
found .... N 4.71, Cl 23.16%.

By recrystallizing this product from 22.5 times the amount of 90% ethanol, it became Ammonium salts 85% yield in the form of also at 195 to 197 ° C with decomposition melting, shiny, plate-shaped crystals obtained.

1.54 g (0.005 mo!) Obtained in the above manner, 2,3-dichloro-4-butyryl-phenoxyacetic acid ammonium salt were dissolved in 10 ml of water at 70 to 80 ^c C and treated with 0.6 ml conc. Hydrochloric acid added. The free keto acid, which separated out in oily form, crystallized rapidly during cooling. The mixture was placed in the refrigerator for a short time, then the crystalline product was filtered off and washed three times with 2 ml of water each time. The product was dried first in open air, then at 6O ⁰ C in a drying cabinet. 1.42 g (97.5% of theory) of 2,3-dichloro-4-butyryl-phenoxyacetic acid were obtained, mp 114 to 115 ° C. After three recrystallization from benzene, a yield of 93 to 95% was obtained Pure keto acid melting at 114.5 to 115 ° C.

Analysis: C ₁₂ H ₁₂ Cl ₂ O ₄ .

Calculated ... C 49.50, H 4.15, Cl 24.36%;
found .... C 49.53, H 4.20, Cl 24.37%.

Example 2
Manufacture of the starting product

2.47 mol of ethyl monochloroacetate, ethyl monobromessic acid or ethyl monoiodoacetate were reacted with 2,3-dichlorophenol sodium salt in the manner described in Example 1; the analytically pure ethyl 2,3-dichlorophenoxyacetate was obtained in each case with a yield of 70 to 90%; F. 68 to 7O ⁰ C. The best yield was achieved as a starting material in the use of monobromoacetic acid ethyl ester.

Similar results were obtained when the potassium or sodium salt of 2,3-dichlorophenol

ίο was prepared by reacting the phenol with an alcoholic or aqueous-alcoholic solution of the alkali hydroxide and by azeotropic distilling off the water from the reaction mixture mixed with benzene. In contrast, almost quantitative yields could be achieved if the 2,3-dichlorophenol in an ether, z. B. in glycol dimethyl ether, was converted into the sodium salt by reaction with sodium hydride. The purest product obtained in this way melts at 70 ^° C .; Solubility in absolute ethanol at 20 ⁰ C 6.5 g / 100 ml; at 78 ° C 66 g / 100 ml.

Analysis: C ₁₀ H ₁₀ Cl ₁₂ O ₃

Calculated ... C 48.22, H 4.05, Cl 28.47%;
found .... C 48.40, H 4.18, Cl 28.38%.

Implementation according to the invention

From 1.06 mol of the ethyl 2,3-dichlorophenoxyacetate obtained in the above manner, in the manner described in Example 1 and subsequent fractionation in vacuo, ethyl 2,3-dichloro-4-butyrylphenoxyacetate was obtained with a yield of 85 to 90% receive; F. 54 to 56 ° C, bp. _{0, 5188-193} ° C. After recrystallization from a 1: 8 mixture of benzene and gasoline, a pure crystalline ethyl ester with a melting point of 58 to 59 ° C. was obtained.

Analysis: C ₁₄ H ₁₆ Cl ₂ O ₄ .

Calculated ... C 52.68, H 5.05, Cl 22.22%;
found .... C 52.75, H 5.26, Cl 22.26%.

From 0.01 mol (3.19 g) of the ethyl 2,3-dichloro-4-butyryl-phenoxyacetate obtained in this way was in the manner described in Example 1 that melts at 195 to 197 ° C with elimination of water Ammonium salt of 2,3-dichloro-4-butyryl-phenoxyacetic acid produced.

Example 3
Preparation of the starting compounds

a) From a mixture of 58 g (0.263 mol) of 2,3-dichlorophenoxyacetic acid, 240 ml of methanol, 24 ml of methanolic 20% hydrochloric acid solution and 50 ml of benzene, 200 ml of solvent mixture were slowly distilled off over a period of 3 hours. The residue was cooled and crystallized by scratching or seeding, rapidly solidifying to a mass of white needle-shaped crystals. This reaction mixture was for 3 hours at - held for 10 ⁰ C, then the crystals were separated by filtration, washed with 50 ml of methanol at -1O ⁰ C and dried. 56 g of methyl 2,3-dichlorophenoxyacetate (91% of theory) were obtained; 92.5 ° C.

b) The mixture of 22.1 g (0.1 mol) 2,3-dichlorophenoxyacetic acid, 75 ml of absolute ethanol and 2 drops of conc. Sulfuric acid was refluxed for 3 hours. The reaction mixture was then

mixed with 0.2 g powdery calcium carbonate and refluxed for a further 1 hour, then filtered while hot. The ethyl ester crystallizes from the filtrate during cooling in long shiny needles. After cooling down, that became Filtered product, washed with 10 ml of cold absolute ethanol and 10 ml of gasoline and dried. The at Ethyl 2,3-dichlorophenoxyacetate melting at 68 to 70 ° C was obtained with almost quantitative yield.

Implementation according to the invention

The starting materials obtained in the above manner were according to Example 1 in 2,3-dichloro-4-butyryl-phenoxyacetic acid-methyl- or converted to ethyl ester.

A. The solution of 0.01 mol of ethyl 2,3-dichloro-4-butyrylphenoxyacetate or methyl ester in 10 ml of ethanol was with 0.4 ml of water and 0.011 mol n-butylamine added. The mixture was allowed to stand at room temperature for 6 hours and then Heated under reflux for 1 hour. A small amount of benzene was then added to the mixture Evaporated dry and the residue from a mixture of benzene and gasoline 1: 1 recrystallized. The n-butylamine salt of 2,3-dichloro-4-butyryl-phenoxyacetic acid obtained in this way melts at 96 to 97 ° C.

Analysis: C ₁₆ H ₂₃ Cl ₁₂ NO ₄ .

Calculated ... N 3.84, Cl 19.47%;
found .... N 3.79, Cl 19.55%.

B. 0.01 mol of 2,3-dichloro-4-butyryl-phenoxyacetic acid methyl ester or ethyl ester was dissolved in 15 ml of benzene and the solution was treated with 0.4 ml of water and 0.011 mol of diethylamine. The mixture was stirred at 25 to 30 ^° C. for 8 hours, then half of the solvent was distilled off and 10 ml of gasoline were added to the residue. During cooling, the diethylamine salt of 2,3-dichloro-4-butyryl-phenoxyacetic acid crystallizes out of the solution. The product separated by filtration was washed with a mixture of benzene and gasoline i: i and dried. The diethylamine salt obtained with at least 90% yield melts at 134 to 136 ⁰ C; the melting point increases after recrystallization from a mixture of benzene and gasoline 1: 1 to 136-137 ° C

Analysis: C ₁₆ H ₂₃ Cl ₂ NO ₄ .

Calculated ... N 3.84, Cl 19.47%;
found .... N 3.84, Cl 19 ^ 63%.

C. The solution of 6.1 g (0.02 mol) of methyl 2,3-dichloro-4-butyryl-phenoxyacetate in 30 ml of benzene was admixed with 0.7 ml of water and 0.02 mol of piperidine. The mixture was allowed to stand at room temperature for 10 hours and then refluxed for 1 hour. 10 ml of benzene were then distilled off from the reaction mixture, and 25 ml of gasoline were added to the still hot reaction mixture. After standing for a few hours, the precipitated salt was filtered off. The piperidine salt of 2,3-dichloro-4-butyryl-phenoxyacetic acid obtained with almost quantitative yield had a melting point of 130 to 132 ° C .; the product recrystallized from a mixture of benzene and gasoline 1: 1 melts at 132 to 133 ^: C.

Analysis: C ₁₇ H ₂₃ Cl ₂ NO ₄ .

Calculated ... N 3.72, Cl 18.84%:
found .... N 3.66, Cl 18.93%.

D. The procedure was as under C, but instead of piperidine an equivalent amount of morpholine used for salt formation. The pure morpholine salt of 2,3-dichloro-4-butyryl-phenoxyacetic acid obtained with a yield of 85 to 90% melts at 120 to 122 ° C.

Analysis: C ₁₆ H ₂₁ Cl ₂ NO ₅ .

Calculated ... N 3.70, Cl 18.75%:
found N 3.61, Cl 18.59%.

E. 0.01 mol of 2,3-dichloro-4-butyryl-phemoxyacetic acid methyl ester or ethyl ester were suspended in 30 ml of 5% hydrochloric acid and taken for 6 hours Heated to reflux. The ketonic acid precipitated in crystalline form during cooling was filtered, three times with 5 ml of water each time, then with 3 ml of ice-cold 50% ethanol and finally with 3 ml Benzene washed. In this way the free 2,3 - dichloro - 4 - butyryl - phenoxyacetic acid was at least 90% yield obtained, m.p. 110 to 112 ° C.

After recrystallization from 3.5 times the amount of benzene, the product melts at 114 to 115 ° C.

F. 0.6 g of crude produced according to E, at 110 to 112 ° C Melting 2,3 - dichloro - 4 - butyryl - phenoxyacetic acid was dissolved in 3 ml of benzene and the solution mixed with 0.15 ml of diethylamine. The immediate onset of excretion of the crystalline diethylamine salt was completed by the addition of 3 ml of gasoline. After filtering, washing with two Portions of 0.5 ml each of a 1: 1 benzene-gasoline mixture and after drying the crystalline product, 0.72 g of the diethylamine salt of 2,3-dichloro-4-butyryl-phenoxyacetic acid was obtained (96.2% of theory) obtained, mp 136 to 137 ° C.

Claims (1)

Claim: Process for the preparation of 2,3-dichloro-4-butyryl-phenoxyacetic acid or its ammonium salts of the general formula I. H ₃ C — CH ₂ —CH ₂ —CO-y ^r ~ \ -O — CH ₂ -COO-NHR ₁ R ₂ R ₃ (I) by acid hydrolysis in the free 2,3-dichloro-4-butyryl-phenoxyacetic acid and this given if converted into the ammonium salt of the general formula I or the 2,3-dichloro-4-butyryl phenoxyacetic acid methyl or ethyl ester in a known manner directly into the corresponding Ammonium salt of the general formula I and this optionally into the free acid caught. Cl Cl