CS205961B1 - Method of preparation of the o,o-dimethyl/2-diethylamino-4-methyl-6-pyrimidinyl/thiophosphate - Google Patents

Description

The invention relates to a novel process for the preparation of O, O-dimethyl-O- (2-diethylamino-4-methyl-6-pyrimidinil) thiophosphate, which is known as an excellent insecticidal composition with relatively low toxicity to warm-blooded animals.

Already in British patent no. 1,019,227, pyrimidine derivatives of the general formula have been described

wherein R _b R ₂ , R ₅ may be the same or different alkyl or alkenyl radicals of up to 6 carbon atoms, or R 1 and R ₂ together with the adjacent nitrogen atom form a heterocyclic radical, R ₃ and R ₄ represent hydrogen, an alkyl or alkenyl radical with up to 6 carbon atoms and X represents an oxygen or sulfur atom. The preparation of these compounds can be illustrated by the scheme:

205 961 wherein R _{1 (} to R ₅ are as previously defined, R is hydrogen or an alkali metal and Y is halogen. From the numerous preparation examples given above, it is apparent that the reactions between substituted pyrimidinols and Ο, Ο-dialkylchlorothiophosphates, in benzene, and in the presence of potassium carbonate or triethylamine as the hydrogen chloride-binding agent, proceeds very slowly over 11 to 30 hours. 3 hours reaction time, but not the yield of the expected O, O-diethyl-O- (2-dimethylamino-4-methyl-6-pyrimidinyl) thiophosphate.

However, the actual preparation of O, O-dimethyl-O- (2-diethylamino-4-methyl-6-pyrimidinyl) thiophosphate in this case | this has not been described in the patent specification. The Czechoslovak patent 154596 discloses a protected process for the preparation of O, O-dimethyl-O- (2-dimethylamino-4-methyl-6-pyrimidinyl) thiophosphate by reacting a compound of formula h ₃ c - X XOR

N.

N (C, H ₅ ) ₂ wherein R is hydrogen or an alkali metal, with a compound of formula YP (S) (OCH ₃ ) ₂ , wherein Y is halogen, optionally in the presence of an acid-binding agent.

However, the example section describes the preparation of O, O-dimethyl-O- (2-diethylamino-4-methyl-6-pyrimidinyl) thiophosphate only by reacting 2-diethylamino-4-methyl-6-hydroxypyrimidine with O, O-dimethylchlorothiophosphate in the presence of potassium carbonate, in ethyl acetate. In this case too, to achieve an 80% yield, it was necessary to maintain the reaction mixture at the boiling point of the solvent overnight.

The disadvantage of the use of alkali carbonates as the reaction-binding compounds of the hydrogen halide produced is, in particular, in an unreasonably long reaction time and in relatively low yields of the products obtained. Substituted hydroxypyrimidines as very weak acids (e.g. 2-diethylamino-4-hydroxy-6-methylpyrimidine pK _a = 9.9) practically do not form the corresponding alkali metal salts of hydroxypyrimidines with alkali metal carbonates, causing very long reaction times when used for the preparation of spit substituted pyrimidinylthiophosphates.

It has now been found that O, O-dimethyl-O- (2-diethylamino-4-methyl-6-pyrimidinyl) thiophosphate can advantageously be prepared when the 2-diethylamino-4-methyl-6-hydroxypyrimidine and the alkali hydroxides are predetermined. the prepared alkali salts are reacted with Ο, Ο-dimethylchlorothiophosphate in an inert organic solvent.

The alkali hydroxides used may be sodium, potassium, or a mixture thereof, in solid form or in aqueous solution. Suitable inert organic solvents include, for example, benzene, toluene, xylene, chlorobenzene or mixtures thereof; of metals react with the hydroxypyrimidines in inert organic solvents already cold to form salts. The water produced by the reaction can advantageously be removed from the reaction mixture by azeotropic distillation. The resulting hydroxypyrimidine alkali salt suspension is then reacted at 50 to 140 ° C for 0.5 to 3.5 hours. Isolation of the product is then carried out in a conventional manner, after removal of the salts and washing of the organic layer; distilling off the solvent under reduced pressure. The importance of the novel process according to the invention lies in the use of alkali hydroxides for the preparation of the alkali salts of 2-diethylamino-4-methyl-6-hydroxypyrimidine and their extremely high reactivity with O, O-dimethylchlorothiophosphate.

Another advantage of the novel process according to the invention is that O-dimethyl-O- (2-diethylamino-4-methyl-6-pyrimidinyl) thiophosphate can be prepared by 15% higher yields compared to the prior art.

The novel process for the preparation of O, O-dimethyl-O- (2-diethylamino-4-methyl-6-pyrimidinyl) thiophosphorus is illustrated but not limited to the following examples.

Example 1 205 961

To a toluene solution prepared from 18.7 g (0.1 M) of 96.9% 2-diethylamino-4-hydroxy-6-methylpyrimidine and 300 ml of toluene was added 6.6 g (0.1 M) with stirring. solid 85% potassium hydroxide. Stirring and heating the slurry formed potassium SO, of which ^one water removed by azeotropic distillation. After distilling off the water and 100 ml of toluene, the reaction mixture is cooled to 70 ° C, 17.6 g (0.11 M) of Ο, Ο-dimethylchlorothiophosphate are added and stirring is continued at 70-75 ° C for 2.5 hours. After cooling from the reaction mixture, wash with water,

3% sodium hydroxide and water remove potassium chloride and unreacted hydroxypyrimidine to neutral pH. 30.5 g of O, O-dimethyLO- (2-) were obtained from the toluene layer after distilling off toluene under reduced pressure by means of a water pump and distilling off unreacted Ο, Ο-dimethylchlorothiophosphate by heating for 2 hours at 70 ° C and 26.6 Pa. diethylamino- (4-methyl-6-pyrimidinyl) thiophosphate. The yield of the product of 96.9% purity, determined by gas chromatography, is 96.9%, calculated on hydroxypyrimidine.

Example 2

To a benzene solution prepared from 18.7 g (0.1 M) of 96.9% 2-diethylamino-4-hydroxy-6-methylpyrimidine and 300 ml of benzene is added 10.2 g (0.1 M) of 40 g. % sodium hydroxide. The reaction mixture is gradually heated under stirring to the boiling point of the mixture, water and 100 ml of benzene are distilled off azeotropically. 17.6 g (0.11 M) of Ο, Ο-dimethylchlorothiophosphate are then added and stirring is continued for 3.5 hours at reflux. The procedure is as in Example 1. 31.5 of a crude product with a purity of 90.8% are obtained, with a yield of 93.7%.

Example 3

A mixture consisting of 300 cm ^{3 of} xylene, 18.7 g (0.1 M) of 2-diethylamino-4-hydroxy-6-methylpyrimidine and 6.6 g (0.1 M) of solid 85% potassium hydroxide is heated in 100 cm ^{3 of} xylene are distilled off azeotropically. 17.6 g (0.11 M) of Ο, Ο-dimethylchlorothiophosphate are added at 130 ° C and the reaction mixture is stirred at 130-135 ° C for a further 0.5 hours. Isolation of the product from the reaction mixture of Example 1 gave 31 g of crude product with a purity of 81.0% in a yield of 82.5%.

Example 4

Mixture consisting of 300 cm ^{3 of} toluene, 18.7 g (0.1 M) of 2-diethylamino-4-hydroxy-6-methylpyrimidine, 1.66 g (0.025 M) of solid 85% potassium hydroxide and 3.1 g The solid sodium hydroxide (0.075 M) is heated to boiling and water and 100 cm ^{3 of} toluene are distilled off azeotropically. After addition of 17.6 g (0.11 M) of Ο, Ο-dimethylchlorothiophosphate at 70 ° C, the reaction mixture is heated with stirring at 70-75 ° C for 3.5 hours. Following the procedure of Example 1, 31 g of crude product with a purity of 89% were obtained in a yield of 90.5%.

Claims (1)

Example 1 205 961 After a toluene solution prepared from 18.7 g (0.1 M) of 96.9% 2-diethylamino-4-hydroxy-6-methylpyrimidine and 300 ml of toluene, 6.6 g is added with stirring. (0.1 M) solid 85% potassium hydroxide. With stirring and heating, a slurry of potassium is formed, of which water is azeotropically distilled. After distilling off the water and 100 ml of toluene, the reaction mixture is cooled to 70 ° C, 17.6 g (0.11 M) of β-dimethylchlorothiophosphate are added and stirring is continued for 2.5 hours at 70 to 75 ° C. . After cooling from the reaction mixture, washing with water, 3% sodium hydroxide and water to neutral pH removed potassium chloride and unreacted hydroxypyrimidine. 30.5 g of O, O-dimethyl O- was obtained from the toluene layer by distilling off the toluene under reduced pressure by means of an aqueous pump and distilling off unreacted Ο, Ο-dimethylchlorothiophosphate for 2 hours at 70 ° C and a pressure of 26.6 Pa. 2-diethylamino-4-methyl-6-pyrimidinyl) thiophosphate. The product yield of 96.9% by gas chromatography was 96.9%, calculated on hydroxypyrimidine. Example 2 To a benzene solution prepared from 18.7 g (0.1 M) of 96.9% 2-diethylamino-4-hydroxy-6-methylpyrimidine and 300 ml of benzene was added 10.2 g (0.1%). M) 40% sodium hydroxide. The reaction mixture was gradually heated with stirring to the boiling point, water and 100 ml of benzene were distilled off azeotropically. Then 17.6 g (0.11 M) of Ο-dimethylchlorothiophosphate are added and stirring is continued under reflux for 3.5 hours. Next, proceed as in Example 1. 31.5 crude product with a purity of 90.8% is obtained, with a yield of 93.7%. Example 3 A mixture consisting of 300 cm 3 of xylene, 18.7 g (0.1 M) of 2-diethylamino-4-hydroxy-6-methylpyrimidine and 6.6 g (0.1 M) of solid 85% potassium hydroxide the mixture is heated under stirring, 100 cm @ 3 of xylene is distilled off azeotropically. 17.6 g (0.11 M) of Ο-dimethylchlorothiophosphate are added at 130 ° C and the reaction mixture is stirred at 130-135 ° C for 0.5 h. Isolation of the product from the reaction mixture of Example 1 yields 31 g of crude product with a purity of 81.0% in a yield of 82.5%. Example 4 A mixture consisting of 300 cm 3 of toluene, 18.7 g (0.1 M) of 2-diethylamino-4-hydroxy-6-methylpyrimidine, 1.66 g (0.025 M) of solid 85% potassium hydroxide and 3 1 g (0.075 M) of solid sodium hydroxide is heated to boiling and water and 100 cm @ 3 of toluene are distilled off azeotropically. After the addition of 17.6 g (0.11 M) of β-dimethylchlorothiophosphate at 70 ° C, the reaction mixture is heated under stirring for 3.5 hours at 70 to 75 ° C. Next, as in Example 1, 31 g of a crude product with a purity of 89% was obtained in a yield of 90.5%. OBJECT OF THE INVENTION A method of preparing O, O-dimethyl-O- (2-diethylamino-4-methyl-6-pyrimidinyl) thiophosphate by reacting a 2-diethylamino-4-methyl-6-hydroxypyrimidine salt with O, O-dimethylchlorothiophosphate, allowing the alkali salt of 2-diethylamino-4-methyl-6-hydroxypyrimidine prepared from sodium, potassium or mixtures thereof and 2-diethylamino-4-methyl-6-hydroxypyrimidine in the presence of an inert organic solvent such as benzene, toluene, xylene; chlorobenzene or mixtures thereof followed by azeotropic removal of water and the reaction with cia, Ο-dimethylchlorothiophosphate takes place at a temperature of 50 to 140 ° C.