CS209941B2 - Method of making the 3,3-dimethyl-2-oxobutyric acid - Google Patents

Abstract

1. Process for the preparation of 3,3-dimethyl-2-oxobutyric acid and its salts by the oxidation of 3,3-dimethyl-2-hydroxybutyric acid, characterized in that reaction is carried out in an aqueous alkaline solution with an at least stoichiometric amount of a salt of the hypochlorous acid as oxidizing agent in the presence of a ruthenium catalyst and the 3,3-dimethyl-2-oxobutyric acid is optionally liberated from the solution of its salts.

Description

(54) A method for producing 3,3-dimethyl-2-oxobutyric acid

The process for the preparation of 3,3-dimethyl-2-oxo-butyric acid and its salts by oxidation of 3,3-dimethyl-2-hydroxybutyric acid according to the invention is carried out by reaction in an aqueous-alkaline solution with at least a stoichiometric amount of the alkali metal salt of hypochlorous acid. The presence of ruthenium catalyst at room temperature or at elevated temperature, preferably at temperatures of 40 to 60 ° C, and 3,3-diimethyl-2-oxobutyric acid is optionally released from the solution of its salts.

3,3-Dimethyl-2-oxobutyric acid is necessary as an intermediate for large-scale production by reaction with -thiocarbohydrazide and subsequent methylation at the sulfur-4-amino-6-tertiary-1-3-4-tert-butylthio- 1,2,4-triazin-5 (4H) -one (Metribuzin), ie a selective herbicide which is mainly used in - soybean, tomato and potato cultures.

The present invention relates to 3,3-dimethyl-2-oxo-butyric acid and salts thereof by the catalytic oxidation of ^{3,3-dimethyl-2-hydroxyethyl} xymáselné acid.

3,3-Dimethyl-X-oxobutyric acid is required as an intermediate for large-scale production by reaction with thiocarbohydrazine followed by methylation on the sulfur atom of 4-amino-6-tert-butyl-3-methylthiio-1,2,4-triazine-5 (4HJ-on (Metribuzin)), a selective herbicide used mainly in soy, tomato and potato cultures (cf. Chem. Ber. 97, 2173-8 (1964); U.S. Patents 3,671,523 and 3). 905 801; 3,3-dimethyl-2-oxobutyric acid can be produced by oxidation

3,3-dimethyl-2-hydroxybutyric acid with potassium permanganate (cf. DOS No. 26 48 300).

While this process is also suitable for large-scale production and has been used to produce significant quantities of Metribuzin, it is very expensive due to the high cost of potassium permanganate; in addition, large quantities of manganese dioxide (burel) are produced as a by-product which must be collected and may potentially be harmful to the environment.

It is therefore an object of the invention to provide an improved and more economical production process

3,3-dimethyl-2-oxobutyric acid and / or salts thereof.

This object and other advantages are achieved according to the invention in that 3,3-dimethyl-2-hydroxybutyric acid of the formula (CH3) 5C-CH-COOH

OH ("hydroxy acid") oxidizes in an aqueous-alkaline solution by at least a stoichiometric amount of an alkali metal salt of hypochlorous acid (hypochlorite) in the presence of a ruthenium catalyst at room temperature or elevated temperature, preferably at temperatures of 40 to 60 ° C;

3,3-dimethyl-2-oxobutyric acid (CH3) 3-C-C-COOH

II o

("Ketoacid") is optionally released from the initially obtained solution of its salts.

More preferably, sodium salts of said acids are used for this purpose, although other alkali metal and alkaline earth metal salts may also be used, provided that the salts are soluble in the aqueous reaction medium.

The reaction medium preferably has a pH of up to 13, preferably 10 to 12. As some of the hydroxyl ions are consumed during the reaction, the alkali is either used in excess or added during the oxidation to bring the desired pH value to maintain the right value. If the pH of the solution of 3,3-dimethyl-2-hydroxybutyric acid ("hydroxy-acid") salt falls below 6.0, or if the hypochlorite solution content, based on the free alkaline component, falls to less than about 1.3%, the desired oxidation does not take place at the desired scale, and the further addition of the alkali metal hypochlorite leads only to the cleavage of any keto acid present. In addition, the ruthenium catalyst is converted to a water-soluble form, which is difficult to separate from the solution.

The alkali metal hypochlorite is preferably used in an excess of about 5 to 15% to ensure complete oxidation of the 2-hydroxy acid to the 2-keto acid. The alkali metal hypochlorite can be produced in situ, for example by introducing chlorine gas into an aqueous, alkaline "hydroxy acid" solution containing a catalyst.

The reaction may be carried out at room temperature, but is preferably carried out at elevated temperature, preferably in the range of from 40 to 60 ° C, to accelerate. Temperatures above 60 ° C · are not favorable to the reaction and should be avoided because in this temperature range, pivalic acid is formed as a by-product as a result of decarbonylation.

The ruthenium catalyst is oxidized to a mixture of ruthenate, ruthenate and ruthenium oxide by the action of hypochlorite, with ruthenate predominating. At the end of the reaction, the ruthenium oxide is present as a solid in an amount substantially equivalent to that initially used, so that it is filtered off and can be used for the next oxidation reaction without further treatment. The ruthenium can be added to the reaction solution in the form of a salt or an oxide, with ruthenium dioxide and especially ruthenium oxide hydrate being preferred. The oxygen can be produced, for example, in situ from a salt, for example ruthenium chloride.

The ruthenium oxide is used in a catalytic amount, for example in an amount of 0.01 to 1.0 g / mol, preferably 0.1 to 0.5 g / mol of the "hydroxy acid".

The aqueous solution of the "hydroxy acid" salt containing the catalyst is brought to the desired pH and heated to the desired temperature. Aqueous sodium hydroxide is then added and chlorine is introduced or the sodium hypochlorite (NaOCl) produced is added dropwise or added dropwise in the form of an aqueous solution. Upon completion of the addition of all oxidizing agent, the reaction mixture is allowed to stand until the end of the reaction, and then the reaction mixture is filtered to separate the catalyst from the solution containing the desired product, i.e. the 3,3-dimethyl-2-oxobutyric acid salt, in high yield, and purity.

From this solution, the "ketoacid" can be liberated in a conventional manner by acidification with a mineral acid, for example hydrochloric acid, and optionally isolated in high yield and high purity.

Oxidation proceeds rapidly and the addition of hypochlorite in only 5 minutes leads to very high yields. Preferably, however, longer reaction times of from 30 minutes to 1 hour are maintained to allow the ruthenium co-catalyst to be converted to a suitable insoluble form, which is then filtered off and can be reused for the next reaction batch. The solution obtained by simple filtration can be used immediately for reaction with thiocarbohydrazine to give 4-amino-6-tert-butyl-3-thio-1,2,4-triazin-5 (4H) -one.

Chemical Communicatlons, 1420 (1970) discloses that compounds containing the group -CHOH-CO- during oxidation using ruthenium as a catalyst undergo cleavage of the carbon-carbon bond and not by conversion to the -CO-CO group. -, for example

- CH OH-CO ---------> - CHO * OHC -CHOH- co- —l · -> -co - co Surprisingly, however, using the starting materials of the invention in an alkaline-aqueous reaction medium, oxidation under converting the 2-hydroxy group to a 2-carbonyl group without cleavage between the Cl and C-2 carbon atoms bearing the hydroxy or carbonyl group.

The invention is illustrated by the following examples.

Example 1

(a) A 2-liter round-bottomed flask equipped with a mechanical stirrer, thermometer, condenser and dropping funnel is charged with 559 g of an 11,8% aqueous solution of 3,3-dimethyl-2-hydroxybutyric acid ("hydroxyacid") in the form of the sodium salt (0.5 mol) and 0.2 g of ruthenium dioxide hydrate (RuOdbO). The pH is adjusted to 12 and the temperature is adjusted to 40 ° C. 330.5 g of 12.1% sodium hypochlorite (0.5 mol -f- 7.5% excess) in water are then added dropwise with rapid stirring over 30 minutes, and the temperature is maintained at 40 DEG C. with an ice bath during the addition. C. After the addition was complete, the ice bath was removed, the solution was stirred for 1 hour and then filtered to remove the catalyst. 879 g of a 7,5% aqueous solution of 3,3-dimethyl-2-oxobutyric acid ("keto acid") are obtained in the form of the sodium salt. Yield: about 100%.

b) Upon completion of the oxidation, the ruthenium catalyst is present in the form of black, water-insoluble ruthenium dioxide hydrate. The catalyst is filtered off using a filter aid ("Celite"). The wet filter cake consisting of the catalyst catalyst and filter aid is immediately added to another amount of the hydroxyacid solution and as described above, further oxidation is performed with the addition of hypochlorite.

с) К 956 g of a 15,8% solution of thiocarbohydrazide in dilute hydrochloric acid are added, within 10 minutes with rapid stirring at 70 ° C, 2 682 g of a 7.27% "ketoacid" filtrate (heated to 70 ° C) produced by the method described in paragraph a). After four hours at 70 degrees Celsius at pH 1.3, the solution was cooled and filtered. The solid thus obtained was washed with water and air-dried. 272.2 g (99.3% purity) of 4-amino-6-tert-butyl-3-thio-1,2,4-triazin-5 (4H) -one are obtained.

Example 2

A four-necked round-bottomed flask equipped with a stirrer, thermometer and 1 liter dropping funnel was charged with 524 g of an aqueous solution containing 0.5 moles of "hydroxy acid" and 100 mg of ruthenium dioxide hydrate. The temperature is maintained at 15 ° C using an ice bath and 294 g of a 11.9% sodium hypochlorite solution are added dropwise with stirring over 1.5 hours. The solution was then allowed to warm to room temperature with stirring over 1 hour. After filtration through glass filter paper (GFA trade name) and / washing of ruthenium dioxide with a small amount of dilute sodium hydroxide, 829 g of a solution containing 7.25% of "keto acid" are obtained. Despite the low reaction temperature and the low amount of catalyst, the yield was 94.4 percent.

Example 3 (comparative example)

The procedure is as described in Example 1, but operating at 80 ° C. In about 30 minutes, 427.4 g (3.5% excess) of 9.0% sodium hypochlorite were added to 555 g of 11.7% "hydro-acid" containing 0.4 g of ruthenium oxide hydrate. After filtration, 982 g of a solution containing> 5.82% ketoacid (87.9%), 0.44% unreacted "hydroxyacid" [6.5%] and 0.32% (6.6% yield) are obtained. pivalic acid in the form of its salt. Accordingly, at higher temperatures, small amounts of pivalic acid are formed as a by-product.

Example 4

The procedure is as in Example 1; Sodium hypochlorite was added at a constant rate over 5 minutes while maintaining the temperature of the reaction mixture at 40 ° C. 982 g of a solution containing 6.36% of 'ketoacid' (96.1% yield) is obtained, which no longer contains any unrecognized 'hydroxy acid'. 0.3 g of ruthenium dioxide is used. Due to the low temperature, the formation of pivalic acid was prevented, but a faster addition compared to Example 1 results in less yield loss.

Example 5

The procedure of Example 4 was repeated but sodium hypochlorite solution was added over 2 hours to give 983 g of a solution containing 6.55% "keto acid" (99 percent yield).

Example 6

The procedure described in Example 1 is repeated using a glass and platinum electrode, which are connected to a pH meter together with a recording device (10 mV). Sodium hypochlorite (supplied at a constant rate by means of a metering pump. The solution voltage is maintained at 336-400 mV. At the end of the reaction the voltage rises to 500 mV and at this point the sodium hypochlorite supply is ordered. 921 g of a solution containing 6.7% of "keto acid" (95% yield) are obtained.

Example 7

To a mixture of 120 ml water, 100 ml 50% sodium hydroxide solution, 1 g

Claims (6)

Subject Process for the preparation of 3,3-dimethyl-2-oxobutyric acid and its salts by oxidation of 3,3-dimethyl-2-hydroxybutyric acid, characterized in that the reaction is carried out in an aqueous-alkaline solution with at least a stoichiometric amount of a hypochlorous acid salt. with an alkali metal oxidizing agent in the presence of a ruthenium catalyst at room temperature or preferably at temperatures of 40 to 60 degrees Celsius and 3,3-dimethyl-2-oxobutyric acid are optionally released from the solution of their salts. Process according to claim 1, characterized in that the pH of the reaction medium is adjusted to a value of 9 to 13, preferably 10 to 12. 3. A process according to claim 1, characterized in that chlorine gas (about 0.5 g / min) is fed with ruthenium (RuO2. H2O) and 0.5 moles of “hydroxy acid” (559.3 g of a 11.8% solution). . The temperature is maintained at 0-5 ° C and after the addition of about 0.7 mol of chlorine, the solution is warmed to room temperature and filtered. 839 g of a solution are obtained containing 7.05% 'keto acid' (91% yield) and 0.38% 'hydroxy acid' (4.8% yield). Example 8 The procedure described in Example 1 was repeated using ruthenium chloride hydrate. A solution of 511.6 g of 12.9% “hydroxy acid” containing 0.3 g of RuCh. H 2 O was added dropwise with 350.5 g of 11.4% sodium hypochlorite solution. 818.7 g of a solution containing 7.35% of 'ketoacid' are obtained (yield 91.3%). Example 1 a d 9 The procedure is as described in Example 1, except that 2'79.7 g of an 11.8% "hydroxyacid" solution is added to the flask and the pH is adjusted to 12. Then 0.3 g of ruthenium dioxide hydrate is added (Rose H 2 O) and 76.8 g of a 26% sodium hypochlorite solution are added dropwise. 341 g of a solution containing 9.53% of "ketoacid" are obtained (yield 100%). YNALEZU that the alkali metal salt of hypochlorous acid is used in a 5-15% excess. 4. Process according to claim 1, characterized in that the ruthenium catalyst is used in an amount of from 0.01 to 1 g, preferably 0.1 to 0.5 g, per 1 mol of 3,3-dimethyl-2-hydroxybutyric acid. . Process according to Claim 1, characterized in that ruthenium oxide hydrate or ruthenium chloride hydrate is used as the ruthenium catalyst. 6. The process of claim 1, wherein a mixture of 3,3-dimethyl-2-hydroxybutyric acid and a ruthenium catalyst in an aqueous alkaline solution is added and an alkali metal salt of chloric acid is added.