CH645340A5 - METHOD FOR PRODUCING PURE, STORAGE-RESISTANT ACETOACETAMIDE. - Google Patents

Description

The invention is therefore based on the object of providing a process for the preparation of acetoacetamide by reacting diketene and ammonia in the presence of chlorinated hydrocarbons, which not only gives pure, storage-stable acetoacetamide in high yield but also in one of the highest purity requirements sufficient form enables this goal to be achieved in only one process step without additional cleaning measures.

This object is achieved according to the invention in that the reaction is carried out with a molar excess of diketene of 0.01 to 2% and at a temperature of <+ 10 ° C.

The stated diketene excess corresponds to a molar ratio of diketene to ammonia of 1,0001 to 1.02: 1. A diketene excess of 0.3 to 1.0% is preferably used, corresponding to a molar ratio of diketene: ammonia of 1.003 to 1.01: 1.

The stated amounts of excess diketene are dimensioned such that an aqueous extract of the reaction mixture obtained has a pH of 6 to 7.

The process according to the invention is carried out in the presence of chlorinated hydrocarbon, which includes practically water-insoluble aliphatic chlorinated hydrocarbons with a boiling point <100 ° C., such as 1,1,1-tri-chloroethane, 1,2-dichloroethylene, perchlorethylene and chloroform, where dichloromethane is used has proven particularly successful. Acetoacetamide is only very slightly soluble in these chlorinated hydrocarbons at working temperatures of <+ 10 ° C and is obtained in suspension. The amount of chlorinated hydrocarbons used is therefore expediently such that the content of solid acetoacetamide in the resulting suspension is about 20 to 35% by weight so that it is still conveyed or. remains pumpable.

In one embodiment of the process according to the invention, diketene and ammonia are simultaneously introduced into the chlorinated hydrocarbon in the anhydrous state, vigorous movement ensuring good distribution of the reactants and the acetoacetamide formed, and the heat of reaction which arises from the exothermic reaction must be removed by good cooling to ensure that the specified temperature is not exceeded. The process according to the invention can be carried out batchwise or continuously at temperatures in the range from −5 ° C. to + 9 ° C. For economic reasons, however, temperatures in the range from + 5 ° C to + 8 ° C are advantageous, since less complex cooling measures are required for this.

It is crucial for the implementation of the method according to the invention that there is no excess ammonia at any point in the reaction, which can be done, for example, by regulating the quantitative ratio of the reactants in a continuous process or by submitting part of the required diketene in the chlorinated hydrocarbon at dis5

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continuous process control can be achieved. According to a preferred embodiment, only the defined excess of diketene is introduced into the chlorinated hydrocarbon and diketene and ammonia are added in stoichiometric amounts, i.e. initiated in a molar ratio of 1: 1. 5

Depending on the reaction conditions chosen (rate of addition, reaction temperature and concentration of the resulting suspension of acetoacetamide), the residence time or reaction time can be between 30 and 180 minutes. io

The acetoacetamide can be separated from the resulting suspension in the usual way by filtration or centrifugation, temperatures of <+ 10 ° C. also having to be observed in order to avoid losses due to the solution of the acetoacetamide. After drying at 15 temperatures up to about 50 ° C under reduced pressure, the acetoacetamide is obtained with a purity of at least 99%, which is practically unchanged at room temperature without further cleaning or stabilization measures. - 20th

Chlorinated hydrocarbon or the mother liquor obtained as filtrate can be circulated in whole or in part together with fresh chlorinated hydrocarbon after they have been washed with water and / or dilute alkali metal or alkaline earth metal hydroxide solution. 25th

The washing process can be carried out continuously or discontinuously at room temperature, with the use of dilute alkaline solutions not exceeding 10% by weight of alkali metal hydroxide, preferably sodium or alkaline earth metal hydroxide, in order to ensure good layer separation 30 in chlorinated hydrocarbon and aqueous phase to reach.

After the aqueous phase has been separated off, the mother liquor purified in this way can be reused without any further drying measures, i.e. be used again in the reaction of diketene and ammonia by the process according to the invention.

The process according to the invention not only avoids the formation of by-products which can arise when excess ammonia is used, such as / 3-aminocro-tonic acid amide and secondary products, but also surprisingly the formation of by-products which occur when excess excess is used Like acetylpyridine derivatives, diketene is almost completely suppressed.

In addition, it was by no means foreseeable that despite the excess diketene used, which is demonstrably present in the resulting reaction mixture (pH value 6 to 7 in the aqueous extract), an acetoacetamide whose purity cannot be obtained after simple removal and drying only meets the highest requirements immediately after production, but remains unchanged even after long storage. In contrast to this, it was demonstrated that when using excess ammonia, which is also detectably present in the resulting reaction mixture (pH value of <10 in the aqueous extract), not only by-products are produced in detectable 55 quantities, but also immediately after production The degree of purity of the acetoacetamide obtained is not retained unchanged, as a result of which the previously assumed decomposition-preventing or stabilizing effect of ammonia on the acetoacetamide is contradicted. 60

In the following examples, the% values given are in each case based on the weight, unless stated otherwise.

Example 1 65

700 kg of dichloromethane and 1 kg of diketene (99.5% strength) were placed in a reaction vessel equipped with brine cooling and a stirring device and cooled to 0 ° C. with stirring. With further cooling and stirring, 44.9 kg of gaseous ammonia and 223 kg of diketene (99.5%) were introduced simultaneously over the course of 2 hours. The reaction temperature was kept at 0 to 3 ° C during the introduction.

The mixture was then stirred at 3 ° C for 1 hour. The resulting suspension - whose aqueous extract (100 ml of suspension was shaken out with 10 ml of distilled water and the pH of the aqueous phase was measured) had a pH of 6.9 - was centrifuged.

The resulting solid was dried at 30 ° C / 1.596 Pa.

A total of 253 kg of colorless, powdery,

> 99.5% (H'-NMR) acetoacetamide obtained, that is 94% of theory, based on diketene.

The filtrate was mixed twice with 0.17 parts by weight of water per part by weight of dichloromethane and each stirred for 0.5 hours at room temperature, separated into layers and the dichloromethane phase used again in the reaction of diketene and ammonia.

The quality of the acetoacetamide obtained was unchanged even after the dichloromethane had been circulated ten times. With the same success, chloroform could be used instead of dichloromethane.

Comparative experiment 1

The procedure according to Example 1 was repeated, but with the modification that only dichloromethane was initially introduced and 223 kg of diketene (99.5% pure) and 48.9 kg of gaseous ammonia (108.8% of theory) were added over the course of 2 Hours were initiated.

The suspension obtained, the aqueous extract of which had a pH of 10.1, was worked up as indicated.

252 kg of 98.5% (H'-NMR) acetoacetamide were obtained, in which, in addition to 1.2% (H'-NMR) / 3-aminocrotonic acid amide, the following compounds were also detected: 4-amino-2,4 -Dimethyl-6-oxo-1,4,5,6-tetrahydropyridine-3-car-bonsäureamid and 2,4-dimethyl-6-oxo-l, 6-dihydropyridin-3-carbonsäureamid.

A sample of this was placed at room temperature under the influence of diffuse daylight. After a standing time of 6 weeks, the acetoacetamide was colored yellow, the content had dropped to 97% (H'-NMR).

This comparison test proves that the use of excess ammonia not only produces by-products in detectable quantities, but also that the degree of purity of the acetoacetamide obtained immediately after production is not retained unchanged after prolonged storage.

Example 2

The procedure according to Example 1 was repeated, but with the modification that 2.5 kg of diketene (99.5% strength) were introduced with the dichloromethane.

The suspension obtained, the aqueous extract of which had a pH of 6.0, was worked up as indicated. However, the filtrate was first treated with 0.17 parts by weight of 5% sodium hydroxide solution and then with 0.17 parts by weight of water per part by weight of dichloromethane at room temperature, as indicated in Example 1.

254 kg of colorless, powder and free-flowing,

> 99.5% (H'-NMR) acetoacetamide obtained, that is 94% of theory, based on diketene.

A sample of this was placed at room temperature under the influence of diffuse daylight.

After a standing time of 6 weeks, the content, consistency and color of the acetoacetamide was practically unchanged.

Example 3

For the continuous implementation of the process

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the circulatory apparatus shown schematically in the drawing used. In this, consisting of a scratch cooler (1) operated with brine and the circulation pump (2), 112 parts by weight / h of diketene (99.5%) were made via line (3) and 22.40 parts by weight / h gaseous via line (4) Ammonia, 33 parts by weight / h of fresh and line (15) 317 parts by weight / h of return dichloromethane were introduced via line (14).

With an average residence time of the reaction mixture in the reaction circuit (1) (2) of 30 minutes, 484.40 kg / h suspension of the centrifuge (6) were simultaneously fed via line (5). The temperature in the reaction circuit including the centrifuge was +5 to + 8 ° C. While 157 parts by weight / h of centrifuge-moist acetoacetamide were obtained via line (7), which after drying at 42 ° C. yield 126 parts by weight / h of colorless> 99.5% acetoacetamide, 327 parts by weight / h of mother liquor were obtained via line (8) and via line (9) 55 parts by weight of water were fed to the continuous mixer (10) and the mixture was passed via line (11) into the phase separator (12). From there, the aqueous phase was discharged via line (13) and the purified dichloromethane was again fed to the circulation pump (2) via line (15). Fresh dichloromethane, which consisted predominantly of the dichloromethane obtained during drying of the centrifugal-moist acetoacetamide, was replaced via line (14) to the same extent as with the acetoacetamide via line (7) as residual moisture or via line (13) with the Wash water was discharged.

COMPARATIVE EXPERIMENT 2 Under the conditions according to Example 1 from DE-PS 2 106 650, dike-5 th dissolved in dichloromethane and ammonia in a molar ratio of 1: 1 were continuously added from above in a thin-film evaporator, the upper third of which was equipped with water cooling added. The throughput was 2 mol / h and the temperature in the gas space was 4 cm above the wiper blades 31 to 33 ° C. The reaction solution was cooled to 15 ° C. in an intermediate container, the majority of the acetoacetamide precipitating out. After the product had been suctioned off, 70% of the unpurified mother liquor were returned to the reaction circuit together with fresh dichloromethane.

After repeating this procedure 9 times, the acetoacetamide produced was white after drying, but only 96.5% (H'-NMR), in which, in addition to 2,6-dihydroxy-4-methyl-3-acetyl-pyridine and 2, 4-dihydroxy-6-methyl-3-acetyl-pyridine and acetamide and 2,4-dimethyl-6-oxo-l, 6-dihydro-pyridine-3 - carboxamide were detected.

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This comparison test proves that when stoichiometric amounts of diketene and ammonia and reaction temperatures of> 30 ° C are used in a continuous process and the re-use of the unpurified mother liquor, sufficient selectivity cannot be achieved, as the moderate degree of purity achieved immediately after production shows .

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Claims (4)

645 340 1. Process for the production of pure, storage-stable acetoacetamide by reacting diketene and ammonia in the presence of chlorinated hydrocarbon, characterized in that the reaction with a molar excess of diketene of 0.01 to 2% and at a temperature of <+ 10 ° C is executed. 2. The method according to claim 1, characterized in that the excess of diketene in the chlorinated hydrocarbon is presented. 2nd PATENT CLAIMS 3. The method according to claim 1 or 2, characterized in that the chlorinated hydrocarbon used is washed with water and / or dilute alkali or alkaline earth metal hydroxide solution and then recycled. The production of acetoacetamide by reacting diketene and ammonia in a solution of organic solvents, such as benzene, at temperatures above 30 ° C. is known. The yields achieved with this, however, are only about 42% of theory, since unreacted diketene can continue to react with acetoacetamide due to its known reactivity, in particular at elevated temperature, with the formation of by-products such as 2,4-dihydroxy-6-methyl -3-acetylpyridine and 2,6-dihydroxy-4-methyl-3-acetylpyridine. When working with excess ammonia, however, increased formation of / 3-aminocrotonic acid amide is to be expected, which is capable of subsequent reactions with the formation of 4-amino-2,4-dimethyl-6-oxo-l, 4,5,6-tetrahydropyridine-3-carboxylic acid amide, 2,4-dimethyl-6-oxo-l, 6-dihydropyridine-3- carboxylic acid amide and at an elevated temperature of 3- [3-amino-buten- (2) - oylamino] -butene- (2) -amide. If diketene and ammonia are reacted in aqueous solution at temperatures around 0 ° C, only solutions with a maximum content of 30% by weight acetoacetamide can be obtained (cf. “Methods of Organic Chemistry” by Houben-Weyl, Volume VII / 4, 4th edition, 1968, pages 233 to 234). Concentrated aqueous solutions with a content of up to 85% by weight of acetoacetamide can be obtained by the process described in DE-AS 1 125 418 (which corresponds to GB-PS 828 423). Here, diketene, ammonia and water are introduced at an elevated temperature (20 to 60 ° C) into an aqueous acetoacetamide solution with the same acetoacetamide content as the solution to be produced and the heat is dissipated by cooling. To ensure that a pH of 9.5 to 10 is maintained during the reaction, an excess of ammonia is used. Obtaining crude acetoacet amide from aqueous solutions requires additional process measures, for example evaporation using a thin-film evaporator under reduced pressure in the presence of excess ammonia, which is apparently attributed to a decomposition-preventing or stabilizing effect on the acetoacetamide in the aqueous solution (cf. GB-PS 832 956). It is also known to carry out the reaction of diketene with excess ammonia in a gaseous reaction medium. Although the known difficulties in separating the acetoacetamide from the liquid reaction media can be avoided, this requires large amounts of an inert gas which require the use of a special reaction apparatus (cf. DE-PS 1 112 510, that of GB-PS 858 529 corresponds). This process is therefore associated with an uneconomical effort. The process described in DE-PS 2 106 650 (which corresponds to GB-PS 1 326 861) is used to prepare acetoacetamide in a liquid reaction medium, chlorinated hydrocarbons having proven successful as solvents. The process is carried out continuously using stoichiometric amounts of the reactants diketene and ammonia at temperatures in the range of preferably 20 to 60 ° C. with a residence time of at most 10 minutes. The acetoacetamide is precipitated by cooling the solution, - separated by filtration and the unpurified mother liquor is circulated together with the solvent. The desired product should be obtained in high yield and the formation of by-products of the type specified above should be almost completely prevented. However, it has been demonstrated that even under these conditions, sufficient selectivity cannot be achieved, since the acetoacetamide obtained in this way is obtained with a purity of at most 96.5%.