KR100517726B1 - 3-Chloro-4-[4-methyl-2-(1H-1,2,4-triazol-l-ylmethyl)-1,3dioxolan-2-yl]phenyl 4-chlorophenyl ether - Google Patents

Abstract

The present invention is 3-chloro-4- [4-methyl-2- (1H-1,2,4-triazol-1-ylmethyl) -1,3 dioxolan-2yl represented by the following Chemical Formula 1] The present invention relates to a method for preparing a phenyl 4-chlorophenyl ether compound, and more particularly, to react 1- [2-chloro-4- (4-chlorophenoxy) -phenyl] ethanone with 1,2-propylene glycol and again. Reaction with bromine to synthesize 2-bromomethyl-2- [2-chloro-4- (4-chloro phenoxy) -phenyl] -4-methyl- [1,3] dioxolane and 1,2,4- Triazole or a salt thereof to react with 3-chloro-4- [4-methyl-2- (1H-1,2,4-triazol-1-ylmethyl) -1,3dioxolan-2yl] phenyl 4 The present invention relates to an improved method for preparing a target product in high yield while greatly improving the purity by producing nitrate by synthesizing and purifying -chlorophenyl ether using nitric acid.

Description

Process for the preparation of 3-chloro-4- [4-methyl-2- (1H-1,2,4-triazol-1-ylmethyl) -1,3 dioxolan-2 yl] phenyl4-chlorophenyl ether compound {3-Chloro-4- [4-methyl-2- (1H-1,2,4-triazol-l-ylmethyl) -1,3dioxolan-2-yl] phenyl 4-chlorophenyl ether}

The present invention is 3-chloro-4- [4-methyl-2- (1H-1,2,4-triazol-1-ylmethyl) -1,3 dioxolan-2yl represented by the following Chemical Formula 1] The present invention relates to a method for preparing a phenyl4-chlorophenyl ether compound, and more particularly, to react 1- [2-chloro-4- (4-chlorophenoxy) -phenyl] ethanone with 1,2-propylene glycol and again. Reaction with bromine to synthesize 2-bromomethyl-2- [2-chloro-4- (4-chloro phenoxy) -phenyl] -4-methyl- [1,3] dioxolane and 1,2,4- Triazole or a salt thereof to react with 3-chloro-4- [4-methyl-2- (1H-1,2,4-triazol-1-ylmethyl) -1,3dioxolan-2yl] phenyl 4 The present invention relates to an improved method for preparing a target product in high yield while greatly improving the purity by producing nitrate by synthesizing and purifying -chlorophenyl ether using nitric acid.

The compound represented by Chemical Formula 1 is mainly used as an oral fungicide to protect crops. The method for preparing the compound of Formula 1 is Korean Patent Publication Nos. 87-1021, 87-2035, 87-2036, 87-2037 and US Patent No. 5,266,585, Japanese Patent Laid-Open No. 59-101484 Known in the art. However, these conventional inventions do not show examples of the specific synthesis for Compound 1, and suggest examples for the synthesis of analogous compounds. Among them, the synthesis method of Example 2 proposed in Korean Patent Publication No. 87-1021 is obtained by reacting the following Chemical Formula 2 with Chemical Formula 3 to obtain Chemical Formula 4, and by reacting Bromine to Chemical Formula 4 to synthesize Chemical Formula 5, Formula 6 is synthesized by acting sodium salt of imidazole. There is no mention of the yield and purity of the synthetic compound.

In the above-described method of formula (6), the typical purification method in each step synthesis method is performed by chromatography on a column. However, this method is difficult and economical to apply to industrial synthesis.

However, in general, toxicity and environmental issues are very important for crop protection agents. Therefore, the synthesis of high-purity crop protection agent is significant, and it is a problem to prepare the target product in high purity while maintaining a certain level of yield for the preparation of the compound. However, it is very difficult to synthesize so that the purity of the final product is 95% or more when purified by the general method.

Thus, the present inventors, while synthesizing the compound of Chemical Formula 1, which is useful as a fungicide for crop protection, has been researched to develop a method for simply increasing the purity while maintaining a high production yield, using nitric acid in the purification process. When the salt is formed and refined, the present invention has been completed by finding that the target product can be manufactured in high purity with high production yield.

Accordingly, an object of the present invention is to provide a method for preparing the compound of Formula 1 in high purity and high yield.

In addition, an object of the present invention is to prepare the compound of Formula 1 in an industrially easy and economical way.

Another object of the present invention is to provide a method for simply purifying the compound of Chemical Formula 1.

Hereinafter, the present invention will be described in detail.

The present invention is 3-chloro-4- [4-methyl-2- (1H-1,2,4-triazol-1-ylmethyl) -1,3- represented by the following Chemical Formula 1 useful as a crop protection fungicide. It is characterized by using nitric acid in the course of synthesizing dioxolane-2 yl] phenyl 4-chlorophenyl ether compound.

Referring to the production method of the present invention in more detail as follows.

The present invention is a method for producing a compound of formula (1) in an industrially easy method, the compound of formula (8) to the compound of formula (7) to synthesize the following formula (9), and reacts bromine Next, after synthesizing Formula 10, 1,2,4-triazole is reacted to synthesize Formula 1 as the target compound.

In the final purification of the compound of Chemical Formula 1, which is a target compound of the present invention, nitric acid is added to purify by removing 4-isomer of the following Chemical Formula 11 as an impurity.

According to the present invention, the nitric acid forms a salt with each of the compounds of Formula 1 and Formula 11, and among them, only Formula 11 is dissolved in an organic solvent, preferably toluene or xylene, to precipitate Formula 1 as a target compound. By refine | purifying, the target object can be manufactured with high purity and high yield.

Representative purification methods for each preparation step in the synthesis of these compounds are carried out by chromatography on a column. However, this method is difficult and economical to apply to industrial synthesis. Therefore, in the present invention, a general purification method which is very easy industrially without chromatography on the column was used.

In the present invention, as a result of examining the cause of the problem of lowering the purity in order to determine what impurities affect the purity in the method of preparing the compound of Formula 1, the compound of Formula 9 and 1,2,4-tria As a result of quantifying the main impurity produced when reacting the sol and quantifying the content of the main impurity, the main impurity present in the reaction system together with the target product is 4- {2- [2-chloro-4- (4-Chloro-phenoxy) -phenyl] -4-methyl- [1,3] dioxolan-2-ylmethyl} -4H- [1,2,4] triazole (hereinafter '4-isomer' ), And the content was quantified to confirm that the content of the impurity was generally present in 10 to 20% by weight.

Generally, there is a method of recrystallization and purification to remove 4-isomer, but when it is recrystallized in a common solvent such as hexane, isopropyl ether, toluene, isopropyl alcohol, etc., even if recrystallized to make purity higher than 95% In the solvent, even if the purity is not improved or the purity is improved, in the case of such a solvent, an excessive amount of solvent or a number of recrystallizations have to be performed several times.

In the present invention, as a result of examining various methods for effective purity improvement, it was found that Formula 1 and Formula 11 form salts with nitric acid. In addition, in the present invention, the nitrates formed by Chemical Formulas 1, 11, and nitric acid have little solubility in water as solids, respectively, and in organic solvents, especially toluene and xylene, the nitrates of the compounds of Chemical Formula 11 are represented by Chemical Formula 1. It has been found that the solubility is higher than that of nitrate.

Based on these facts, in the present invention, after removing the reaction solvent and adding a suitable organic solvent and nitric acid to form a crystal, the nitrate of Formula 1, which is a target compound, precipitates mostly as crystals and is a main impurity. Most of the nitrates of Formula 11 are dissolved in organic solvents. That is, a specific organic solvent and nitric acid are added to the final reaction product to obtain a high purity nitrate of Formula 1, and then neutralized and extracted with a suitable solvent, crystallized in a crystallization solvent, filtered and dried to obtain a high purity of 93% or more. Compounds can be obtained.

According to the present invention, a general preparation process and reaction conditions for preparing a target product from Chemical Formula 7, which is a starting material, may be performed in a similar manner to a known method, and nitric acid is preferably 20 to 50% of nitric acid. It is advantageous in terms of handling and economics and the effective production of nitrates in the reaction system. At this time, the amount of the starting material may be used as 80 ~ 300 parts by weight based on 100 parts by weight of the compound of the formula (7), the amount of nitric acid can be appropriately adjusted while looking at the concentration of nitric acid and the reaction process. If too little nitric acid is used, salt formation does not occur properly and the purity is lowered. If too much is used, it is uneconomical and the yield may be lowered.

In addition, the organic solvent used with the nitric acid in the present invention may be any organic solvent that can selectively dissolve only the nitrate of the formula 11 without dissolving the nitrate of the formula (1). For example, toluene or xylene can be preferably used as the organic solvent, and the amount of the organic solvent is sufficient to sufficiently dissolve the nitrate of the formula (11). For example, the organic solvent may be used at 1 to 10 times the weight of nitric acid.

In general, the toxicity and environmental problems are very important in the crop protection fungicides, it is very meaningful that the crop protection agent can be synthesized with high purity. In particular, it is very difficult to synthesize so that the purity of the final product is 95% or more while purifying by an economical and general easy method, in the present invention can be said to be a very advanced manufacturing method in that it solves these difficulties.

As such, the compound of Chemical Formula 1 prepared through the preparation method and the purification process of the present invention can remove impurities without deteriorating the yield of the target object in a very economical and simple manner, compared to the conventional method, and thus can produce the target substance in high purity and high yield. In particular, it is a commercially very useful manufacturing method in that it is environmentally friendly by using a high purity target product.

Hereinafter, the production method and purification process of the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited by Examples.

Example

84 g of heptane, 22 g of 1,2-propylene glycol, 28 g of 1- [2-chloro-4- (4-chlorophenoxy) -phenyl] ethanone and 0.3 g of p-toluenesulfonic acid were placed in a reactor to remove water by azeotropic distillation. It was. When the reaction was completed, the heptane layer was separated, washed with water, and then the water of the heptane layer was removed by azeotropic distillation. Bromine 15.3g was added dropwise at 0-30 占 폚.

After the reaction was completed, 20% caustic soda and distilled. 79 g of N.N-dimethylformamide was added to the distillation filtrate, 18 g of 1,2,4-triazole sodium salt was added, and the reaction was carried out at 150 ° C. for 8 hours, followed by distillation of N.N-dimethylformamide.

 40 g of toluene and 40 g of water were added thereto, stirred and left to separate the water layer. Then, 40 g of 30% nitric acid was added thereto, cooled to 10 ° C, and crystallized. 120 g of toluene was added to the solid obtained after filtration, and it neutralized with caustic soda. After neutralization, the toluene layer was separated and the toluene layer was distilled off. 40 g of isopropyl alcohol was added thereto and crystallized. Filtration and drying gave 22 g (purity 97%) of the title compound, and the filtrate was concentrated and crystallized again to obtain 3 g.

Comparative example

In the above example, 40 g of 30% nitric acid was added thereto, cooled to 10 ° C., crystallized, filtered, 120 g of toluene was added to the filtered solid, and then neutralized and neutralized with caustic soda, and the separation was omitted. Synthesis was carried out in the same manner as to obtain the target compound 24g (purity 84%).

As described above, the present invention is to effectively purify the nitric acid that was not used in the conventional method for producing a crop protection agent represented by the formula (1) in the purification process, it is possible to produce the target compound in high purity, high yield compared to the conventional It works.

In addition, the manufacturing method is also easy to manufacture industrially, very economical and simple, there is a very improved effect in that it is environmentally friendly by using a high-purity target.

Claims (5)

delete By reacting the compound of formula (7) to the compound of formula (8), the following formula (9) is synthesized, and bromine is reacted to synthesize the following formula (10), and then 1,2,4-triazole is reacted to 3-Chloro-4- [4-methyl-2- (1H-1,2,4-triazol-1 ylmethyl) -1,3, characterized in that the compound of 1 is synthesized and purified using nitric acid. -Dioxolan-2yl] phenyl 4-chlorophenoxy ether compound. The method according to claim 2, wherein the nitric acid is added to purify by removing the compound represented by the following formula (11) which is a main impurity. The method according to claim 3, wherein the nitric acid forms a salt with the compounds of Formula 1 and Formula 11, respectively, and precipitates and purifies Formula 1 in a state in which Formula 11 is dissolved in an organic solvent. . The method of claim 4, wherein toluene or xylene is used as the organic solvent.