EP0000042B1 - Process for the preparation of 2,4,5-trichloropyrimidine - Google Patents

Description

The present invention relates to a new process for the preparation of 2,4,5-trichloropyrimidine.

worin

• R und R' einen C₁-C₄-Alkylrest bedeuten

gegebenenfalls in Mischung mit einem inerten Verdünnungsmittel bei Temperaturen von 0 bis 50°C, vorzugsweise 30-40°C, mit weniger als 7,5 Mol Chlor, insbesondere 3,5-7,0 Mol Chlor bezogen auf 1 Mol Ausgangsverbindung, umsetzt und anschließend in Abwesenheit von Chlor auf Temperaturen von 100-150°C, vorzugsweise 110-140°C erhitzt.The process is characterized in that (2-cyanoethyl) dithiocarbamic acid ester of the formula

wherein

• R and R 'represent a C ₁ -C ₄ alkyl radical

optionally in a mixture with an inert diluent at temperatures from 0 to 50 ° C., preferably 30-40 ° C., with less than 7.5 mol of chlorine, in particular 3.5-7.0 mol of chlorine, based on 1 mol of starting compound, and then heated in the absence of chlorine to temperatures of 100-150 ° C, preferably 110-140 ° C.

In a preferred embodiment, chlorination is carried out at temperatures of from about 20 ° C. to about 40 ° C. until the exothermic reaction has ended and then subsequently reheated to temperatures of 110 to 140 ° C. in the absence of chlorine.

Optionally, one may further after heating to 100-150 ⁰ C again at 150-200 ° C, preferably implement 160-190 ° C, with elemental chlorine. Sulfur-containing by-products are converted into 2,4,5-trichloropyrimidine, so that the yield can be increased in some cases.

The chlorine can be used in the chlorination reaction both in the form of elemental chlorine and in the form of customary chlorinating agents, for example sulfur dichloride, sulfuryl chloride, phosphorus pentachloride. Appropriate amounts of chlorinating agent must of course be used, for example instead of 1 mol of CI ₂ 2 mol of SCI ₂ .

zunächst cyanethylierte Amine (11), in denen R die oben genannte Bedeutung besitzt, mit Schwefelkohlenstoff in wäßriger Natronlauge zu den Dithiocarbamaten der Formel (III) umsetzt, welche anschließend durch Alkylierung in die Ester der Formel (I) übergeführt werden, z.B. mit (substituierten) Alkylhalogeniden, Sulfonsäurealkylestern oder Dialkylsulfaten, z.B. mit Dimethylsulfat gemäß folgendem Formelschema:

Although the starting compounds of the formula (I) are not known, they can easily be prepared according to the literature for the preparation of alkyl dialkyldithiocarbamic acid esters (for example J. Chem. Soc. 1944, p. 151) by using the following formula

initially reacting cyanoethylated amines (11), in which R has the abovementioned meaning, with carbon disulfide in aqueous sodium hydroxide solution to give the dithiocarbamates of the formula (III), which are subsequently converted into the esters of the formula (I) by alkylation, for example with (substituted) ) Alkyl halides, sulfonic acid alkyl esters or dialkyl sulfates, for example with dimethyl sulfate according to the following formula:

indem man primäre Amine (IV), in denen R die obengenannte Bedeutung besitzt, an Acrylnitril anlagert;

• (vgl. z.B. J. Am. Chem. Soc. 66, 725 (1944);
• J. Am. Chem. Soc. 68, 1217 (1946);
• J. Am. Chem. Soc. 78, 2573 (1956);
• J. Heterocyclic Chem. 1, 260 (1964);

The cyanoethylated amines (II) are obtained, for example, according to the following formula

by adding primary amines (IV), in which R has the abovementioned meaning, to acrylonitrile;

• (see, for example, J. Am. Chem. Soc. 66, 725 (1944);
• J. Am. Chem. Soc. 68, 1217 (1946);
• J. Am. Chem. Soc. 78: 2573 (1956);
• J. Heterocyclic Chem. 1, 260 (1964);

• (2-Cyanethyl)-methyl-dithiocarbamidsäuremethylester,
• (2-Cyanethyl)-ethyl-dithiocarbamidsäuremethylester,
• (2-Cyanethyl)-methyl-dithiocarbamidsäuremethylester,
• (2-Cyanethyl)-ethyl-dithiocarbamidsäuremethylester,
• (2-Cyanethyl)-methyl-dithiocarbamidsäurepropylester,
• (2-Cyanethyl)-methyl-dithiocarbamidsäurebutylester,
• (2-Cyanethyl)-butyl-dithiocarbamidsäuremethylester.

Examples of suitable (2-cyanoethyl) dithiocarbamic acid esters of the formula (I) for the process according to the invention are:

• (2-cyanoethyl) methyldithiocarbamic acid methyl ester,
• (2-cyanoethyl) ethyl dithiocarbamic acid methyl ester,
• (2-cyanoethyl) methyldithiocarbamic acid methyl ester,
• (2-cyanoethyl) ethyl dithiocarbamic acid methyl ester,
• Propyl (2-cyanoethyl) methyldithiocarbamic acid,
• (2-cyanoethyl) methyl dithiocarbamic acid butyl ester,
• (2-cyanoethyl) butyl dithiocarbamic acid methyl ester.

Diluents which are inert under the reaction conditions are all chlorine resistant solvents e.g. chlorinated aliphatic and aromatic hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, 1,1,2,2-tetrachloroethane, tetrachlorethylene, 1,1,2,3,3-pentachloropropane, hexachlorocyclopentadiene, octachlorocyclopentene, 1,2,4-trichlorobenzene, chlorinated Pyrimidines and phosphorus oxychloride. In general, 0.5 to 20, preferably 1 to 10 parts by volume of diluent are used per part by weight of (I).

In the event that the chlorinating agent is a liquid under the reaction conditions, such as sulfur dichloride or sulfuryl chloride, the additional use of an inert diluent can be omitted.

In connection with sulfur dichloride as the chlorinating agent, disulfur dichloride can be used particularly advantageously as a diluent.

When using chlorine as the chlorinating agent, the reaction is initially very exothermic. It is therefore expedient to work with an excess of chlorine, especially in the case of larger batches, until the exothermic reaction has subsided. After the strongly exothermic first chlorination phase has subsided, in order to end the reaction as quickly as possible, advantageously with an excess of chlorine (recognizable by the greenish color of the chlorination offgas).

The process is carried out in detail in such a way that first a (2-cyanoethyl dithiocarbamic acid ester of the formula (1), in particular the (2-cyanoethyl) methyl dithiocarbamide acid methyl ester, with one of the diluents mentioned, for example chloroform, is added Mixing the room temperature and then adding the chlorinating agent, the external cooling and metering of the chlorinating agent are coordinated so that the initially strongly exothermic reaction does not become too violent and does not exceed 40 ° C.

Chlorination is preferably carried out at 30-4.0 ° C. until the exothermic reaction has completely subsided.

Then stripped in vacuo below 40 ° C still in the reaction mixture dissolved chlorine as well as the ^g by the Chiörierun sreaktion resulting sulfur chloride and heats the residue either continue on in a vacuum or at normal pressure with exclusion of moisture up to about 120-130 ° C, wherein 2,4,5-trichloropyrimidine is formed. The 2,4,5-trichloropyrimidine is separated off by distillation, for example with the aid of an Ag-mirrored packed column of about 1 m in length. It can easily be obtained in a purity of over 99%.

If you are working with a chlorinating agent such as sulfur dichloride that is liquid under the reaction conditions, it is advisable to submit the latter and to meter in part of the starting product (I) at 30-40 ° C.

When using sulfur dichloride as the chlorinating agent, it is particularly advantageous to introduce less than 15 moles of SCI ₂ per mole (I) (corresponding to the above-mentioned less than 7.5 moles of CI ₂ per mole (I)). This eliminates the need to remove excess chlorinating agent in a vacuum below 40 ° C.

2,4,5-Trichloropyrimidine is suitable as a starting component for the production of reactive dyes (reaction with dyes containing amino groups).

2,4,5-trichloropyrimidine can be converted into tetrachloropyrimidine by gas phase chlorination (GB-PS 1 201 228). Tetrachloropyrimidine is suitable as a reactive component for the production of reactive dyes (see e.g. Belgian Patent No. 578 933). In addition, 2,4,5-trichloropyrimidine has fungicidal and sporicidal properties (see US Pat. No. 3,227,612).

mit Chlor beschrieben. Ganz adgesehen davon, daß kein Beispiel für X=S angegeben ist, würde ein solches Verfahren gegenüber dem erfindungsgemäßen erhebliche Nachteile aufweisen, da die Ausgangsprodukte mit X=S nur schwierig herzustellen sind (Reaktion mit dem teuren und sehr giftigen Thiophosgen). Das beschriebene Verfahren legt das erfindungsgemäße in keiner Weise nahe.In French Patent 1,545,314, the production of trichloropyrimidine by reacting aminopropynitriles of the formula is part of a general formula

described with chlorine. Quite apart from the fact that no example for X = S is given, such a method would have considerable disadvantages compared to the invention, since the starting products with X = S are difficult to produce (reaction with the expensive and very toxic thiophosgene). The described method in no way suggests the inventive method.

example 1

670 g (6.5 mol) of sulfur dichloride and (as a diluent) 250 ml of disulfur dichloride are placed at 35 ° C. in a 2 1 three-necked flask equipped with a stirrer, dropping funnel and thermometer. With stirring and occasional cooling with ice water, 87 g (0.5 mol) of molten (2-cyanoethyl) methyldithiocarbamic acid methyl ester are then added dropwise in the course of about half an hour in the temperature range from 35 to 40 ° C. After the addition has ended, the mixture is stirred at 35-4.0 ° for about a quarter of an hour until the evolution of gas has ended. The reaction mixture is then heated with stirring to reflux (137 ° C.) in about 2 hours, a thick precipitate being formed in the range at about 60 ° C., which dissolves again at about 120 ° C. The formation of 2,4,5-trichloropyrimidine is complete when a clear solution is present and no more gas evolution is observed. All parts of the reaction mixture which can be distilled up to a bath temperature of 150 ° C./14 torr are then distilled off. According to gas chromatographic analysis, the distillate contains 78 g (corresponding to 85% of theory) of 2,4,5-trichloropyrimidine.

If a slight excess of chlorine flow (recognizable by the greenish color of the exhaust gas) is passed into the distillation residue from 150 ° C up to an internal temperature of around 180 ° C for 1/2 to 1 hour and then distilled in a water jet vacuum to a bath temperature of 200 ° C from all distillable fractions, a further 4 g (corresponding to about 496 of theory) of 2,4,5-trichloropyrimidine is obtained after gas chromatographic analysis.

Rectification on an Ag-mirrored packed column of 1 m in length gives 2,4,5-trichloropyrimidine at bp ₁₂ 94-96 ° C. in a purity of over 99%.

• Zu einer auf 5°C abgekühlten Lösung von 203 g (5,07 Mol) Natriumhydroxid in 1800 ml Wasser läßt man unter Außenkühlung mit Eis/Wasser zuerst 420 g (5,0 Mol) 3-Methyl-amino-propionitril und danach während etwa 10 Minuten 400 g (5,26 Mol) Schwefelkohlenstoff fließen. Anschließend wird unter weiterer Kühlung im Eisbad ca. 1,5 Stunden kräftig nachgerührt, wobei eine praktisch homogene Phase entsteht. Unter weiterer Eiskühlung werden nun 650 g (5,16 Mol) Dimethylsulfat in dem Maße zugetropft, daß die Reaktionstemperatur ca. 30°C nicht übersteigt. Danach wird die sich abscheidende ölige Schicht gründlich mit Wasser gewaschen, worauf sie zu einer farblosen kristallinen Masse von reinem (2-Cyanethyl)-methyldithiocarbamidsäuremethylester erstarrt. Nach dem Absaugen und Trocknen Schmelzpunkt 45 bis 46°C. Die Verbindung zeigt ein charakteristisches IR-Spektrum mit folgenden Banden (in cm^-1): 2250, 1490, 1425, 1380, 1300, 1250, 1195, 1100, 1030, 985, 955, 755.

The starting product (2-cyanoethyl) methyl dithiocarbamide acid methyl ester was as follows. dimensions received:

• To a solution of 203 g (5.07 mol) of sodium hydroxide in 1800 ml of water which had been cooled to 5 ° C., 420 g (5.0 mol) of 3-methylamino-propionitrile were first added with external cooling with ice / water and then for about Flow 400 g (5.26 mol) of carbon disulfide for 10 minutes. The mixture is then stirred vigorously for about 1.5 hours with further cooling in an ice bath, a practically homogeneous phase being formed. With further ice cooling, 650 g (5.16 mol) of dimethyl sulfate are then added dropwise to the extent that the reaction temperature does not exceed about 30 ° C. The oily layer which separates is then washed thoroughly with water, whereupon it solidifies to a colorless, crystalline mass of pure (2-cyanoethyl) methyldithiocarbamic acid methyl ester. After suction and drying, melting point 45 to 46 ° C. The compound shows a characteristic IR spectrum with the following bands (in cm ^-1 ): 2250, 1490, 1425, 1380, 1300, 1250, 1195, 1100, 1030, 985, 955, 755.

Example 2

The procedure is analogous to Example 1, including post-chlorination at 150-180 ° C, with the difference that instead of 670 g (6.5 mol) of sulfur dichloride, only 360.5 g (3.5 mol) of sulfur dichloride are introduced. According to gas chromatographic analysis, the distillates contain 51.6 g (corresponding to 56.3% of theory) of 2,4,5-trichloropyrimidine.

Claims (3)

1. Process for the preparation of 2,4,5-trichloropyrimidine, characterised in that compounds of the formula

wherein

R and R' represent C₁-C₄-alkyl are reacted at temperatures from 0 to 50°C with less than 7.5 mols of chlorine, in particular 3.5 to 7.0 mols of chlorine, related to 1 mol of the starting compound, and the reaction products are then after-heated to temperatures of 100-150°C, in particular 110-140⁰C, in the absence of chlorine.

2. Process according to Claim 1, characterised in that the chlorination is carried out at temperatures from about 30°C to about 40°C until the exothermic reaction has ended, and the reaction products are then after-heated to temperatures of 110-140°C in the absence of chlorine.

3. Process according to Claim 1, characterised in that after heating to 100-150°C in the absence of chlorine, the reaction products are after-chlorinated at 150-200⁰C with elementary chlorine.