HU202480B - Process for producing 2-phenyl-2-hydroxymalonic acid diamides - Google Patents

Abstract

2-phenyl-2- hydroxy - malonic acid- di:amides are prepd. by dissolving 2-phenyl-malonic acid-di:amides in (1-3C) carboxylic acids or (1-3C) halogenated carboxylic acids prior to treatment with hydrogen-peroxide.

Description

The present invention relates to a novel process for the preparation of 2-phenyl-2-hydroxymalonic acid diamide. The process is carried out by treating 2-phenylmalonic acid diamide with 3 to 15 moles of hydrogen peroxide per mole in the presence of 30 to 140 moles of C 1 -C 3 carboxylic acid or C 2 -C 3 fluorinated carboxylic acid at 20-85 ° C. with.

2-Phenyl-2-hydroxymalonic acid diamides are compounds with significant insecticidal and acaricidal activity.

2-Phenyl-2-hydroxy-malonic acid diamides are described in U.S. Pat. According to Hungarian Patent Application No. 5,198, substituted oxocarboxylic acid derivatives (e.g., nitrile, ester or amide of carboxylic acid) can be prepared by reacting with hydrogen cyanide or a hydrogen cyanide releasing compound (e.g. acetone cyanohydrin, trimethylsyl cyanide) -malonic acid or 2-silyloxy-malonic acid dinitrile, amide nitrile, or ester nitrile and then convert these derivatives into diamide in further reaction steps. The main disadvantage of this process is that it requires highly hazardous chemicals. A further difficulty is that the starting compound, which is usually the nitrile of the oxocarboxylic acid, can be obtained only through a multistep reaction sequence.

Alternatively, one way of preparing substituted 2-hydroxy malonic acid diamides is to prepare the corresponding 2-hydroxy malonic acid ester from mesoxalic acid ester by substituted benzene and tin tetrachloride (J. Org. Chem. 42, 4692, 1982). from which the desired 2-hydroxymalonic acid diamide is readily obtained by ammonia in a known manner (J. Amer. Chem Soc. 441564 1922). This solution is not suitable for an industrial process mainly because of the expensive raw materials and anhydrous conditions required for the reaction,

SUMMARY OF THE INVENTION It is an object of the present invention to provide a process for the preparation of 2-phenyl-2-hydroxymalonic acid diamides without the use of costly and hazardous chemicals in a simpler and more economical manner than the prior art.

The present invention is based on the discovery that 2-phenyl-2-hydroxymalonic acid diamides can be prepared by reacting the corresponding malonic acid diamides with hydrogen peroxide in an organic acidic medium.

The starting materials for the reaction are readily available or can be prepared. Synthesis of malonic acid esters by carbalkoxylation of substituted acetic acid esters has long been known and has been commercially carried out for 2-phenylmalonic acid diethyl ester as an important pharmaceutical raw material (J. Amer. Chem. Soc. 63. 2056 1941). In turn, 2-phenylmalonic acid diamides can be readily obtained from the corresponding malonic acid esters with ammonia, as already mentioned.

According to the present invention, 2-phenylmalonic acid diamide is dissolved in C 1-3 carboxylic acid (formic acid, acetic acid) or C 1-3 halogenated carboxylic acid (monochloroacetic acid, trichloroacetic acid) and hydrogen peroxide is added. The carboxylic acids also provide the acidic medium required for the reaction and are also useful as solvents for the malonic acid diamides which are poorly soluble in commonly used organic solvents.

It has been found that the reaction is carried out in strong acids (formic acid, trichloroacetic acid) at 20-40 ° C, but it is preferable to carry out the conversion at 50-60 ° C to reduce the reaction time. In less strong acids, e.g. in acetic acid, the reaction proceeds at a satisfactory rate only at 70-90 ° C under heating.

The molar ratio of 2-phenylmalonic acid diamide to hydrogen peroxide can be varied within wide limits, depending on the type of carboxylic acid used and the reaction temperature.

The reaction may be carried out using a commercially available 30% aqueous solution of hydrogen peroxide. For practical reasons, a solution of hydrogen peroxide in a concentration of less than 10% by weight is not advisable because the reaction is too slow. When excess hydrogen peroxide is added, it should be noted that the solubility of the 2-phenylmalonic acid diamide will vary depending on the amount of water added to the reaction mixture, so keeping it in solution will require additional acid addition at higher hydrogen peroxide levels.

In our experiments, the hydrogen peroxide can be added to the 2-phenylmalonic acid diamide dissolved in the carboxylic acid simultaneously or in portions. In the latter case, however, the reaction time is increased.

In a preferred embodiment of the present invention, 2-phenylmalonic acid diamide is dissolved in acetic acid and stirred with 30% hydrogen peroxide at 80 ° C for 8-12 hours. The reaction product is recovered from the reaction mixture by chloroform extraction. The material separated by concentration of the extract does not require further purification or recrystallization.

The invention is further illustrated by the following examples, without limiting our claims.

Example 1

2-Methyl-malonic acid diamide (3.56 g, 0.02 mol) was dissolved in acetic acid (50 ml) at 80 ° C. While stirring, 10 ml of 25.2% hydrogen peroxide was added over 20 minutes. The reaction mixture was stirred at 80 ° C for 10 hours, then cooled to room temperature and diluted with 150 ml of water. The reaction mixture, diluted with water, was extracted with chloroform (5 x 70 mL and 5 x 100 mL). The combined chloroform phases were extracted with 50 ml of saturated sodium sulfite solution, dried over sodium sulfate, and the chloroform was evaporated in vacuo. To the distillation residue was added 100 ml of benzene and concentrated in vacuo to 30 ml. During evaporation, the 2-phenyl-2-hydroxymalonic acid diamide crystallizes. The product is filtered off, washed with benzene and dried.

Yield: 1.68 g (43.2%).

Melting point: 159-161 ° C

HU 202 480 B 1 H NMR (DMSO-D 6): 6.25 / s, 1H, OH)

IR (KBr): 1680 cm ^-1 (CO), 3340 cm ^-1,

3170 cm ^-1 (NH, amide), 3440 cm ^-1 (OH)

Example 2

2-Phenylmalonic acid diamide (3.56 g, 0.02 mol) was dissolved in acetic acid (50 ml) at 85 ° C. At this temperature, 5.3 ml of 25.2% hydrogen peroxide was added over 10 minutes. The reaction mixture is stirred at 85 'C for 4 hours, then another 3 ml of hydrogen peroxide is added and the reaction mixture is reacted for a further 3 hours at 85' Con. The reaction mixture was allowed to cool to room temperature and after 16 h was diluted with benzene (500 mL). The lower aqueous layer was separated and the benzene layer was extracted with water (5 x 50 mL). The combined aqueous layers were extracted with benzene (2 x 250 mL). Sodium sulfite solution is added dropwise to the aqueous phase until the potassium iodide solution is no longer colored. The aqueous phase is then extracted with 200 ml of chloroform, the combined chloroform phase is dried and distilled in vacuo and the

Work up as in Example 1.

Yield: 1.25 g (32.2%).

Melting point: 160-161 ° C

The test results for the final product identification are the same as in Example 1.

Example 3

2-Phenylmalonic acid diamide (3.56 g, 0.02 mol) was dissolved in trifluoroacetic acid (50 ml) and hydrogen peroxide (30 ml, 30% w / v) was added. The reaction mixture was allowed to stand at 20-24 ° C and 2-2 ml 30% Hydrogen Peroxide (10%) was added. After nine days, the reaction mixture was diluted with water (100 mL), quenched with excess hydrogen peroxide in sodium sulfite solution. The aqueous solution was decolorized with carbon dioxide (0.2 g) and extracted with chloroform (5 x 300 mL). The combined chloroform layer was dried over sodium sulfate and the chloroform was distilled off in vacuo. The distillation residue 40 was worked up as in Example 1.

Yield: 0.7 g (18.0%)

Melting point: 159-161 ° C

The test results for the final product identification are the same as in Example 1

Example 4

3.56 (0.02 mol) of 2-phenylmalonic acid diamide was dissolved in 100 ml of formic acid and 10 ml of 25.2% hydrogen peroxide 10% was added. The reaction mixture was kept at 20-24 ° C for 24 hours, then at 50 ° C for 5 hours, cooled to 25 ° C, and hydrogen peroxide (10 ml) was added again. After standing for 8 days, another 10 mL of hydrogen peroxide was added and allowed to stand for 15 days.

It is then stirred at 50 [deg.] C. for 4 hours, cooled, diluted with 200 ml of water, extracted five times with 300 ml of chloroform and, after drying over sodium sulfate, distilled under reduced pressure. The residue is processed as described in Example 1.

Yield: 0.85 g (21.9%)

Melting point: 159-161 ° C

The test results for the final product identification are the same as in Example 1.

Claims (2)

PATIENT INDIVIDUAL POINTS A process for the preparation of 2-phenyl-2-hydroxy malonic acid diamide, characterized in that 2-phenylmalonic acid amide is present in an amount of from 3 to 15 moles of horseradish peroxide per mole of 30 to 140 moles of C 1-3 carboxylic acid or 2 In the presence of C3-fluorinated carboxylic acid at 20-85 ° C, the product obtained is recovered from the reaction mixture in a manner known per se, preferably by extraction with chloroform. 2. A process according to claim 1 wherein the carboxylic acid is acetic acid or trifluoroacetic acid