KR970001485B1 - A process for preparing 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1,3,5-thiadiazine-4-one - Google Patents

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Description

High Purity Purification of 2-t-Butylimino-3-isopropyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one

The present invention provides a high purity and high yield of 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one represented by the following structural formula (I): It relates to a method of purification.

In general, the compound represented by the above formula (I) is an important compound used as an insecticide exhibiting strong physiological activity against insects, especially larvae. The preparation method of the compound represented by the above structural formula (I) has been proposed in Japanese Patent Laid-Open Nos. 54-3083, 54-27590, and Korean Patent Publication No. 91-5747, and such a conventional manufacturing method is considered. Try it like this:

In Japanese Patent Laid-Open Nos. 54-3083 and 54-27590, N-chloromethyl-N-phenylcarbamoyl chloride represented by the following structural formula (II) is 1-isopropyl-3- represented by the following structural formula (III). The reaction product was reacted with t-butylthiourea and crystallized with isopropyl alcohol to prepare the target compound represented by Structural Formula (I), wherein the production yield was 65%.

Korean Patent Publication No. 91-5747 discloses p-nitromethyl N-chloromethyl N'-phenylcarbamate represented by the following structural formula (IV) and 1-isopropyl-3-t- represented by the structural formula (III). Synthesis of p-nitromethyl-N- (N'-t-butyl N ''-isopropyl isothioureido) methyl-N-phenylcarbamate represented by the following structural formula (V) using butylthiourea After completion of the reaction by aging in chlorochloroethane, dichloromethane, acetonitrile solvent, or a mixture of the solvent and water, the reaction was completed and solidified in isopropyl alcohol to prepare the target compound represented by the formula (I).

In the above-mentioned conventional production methods, the production methods shown in Japanese Patent Laid-Open Nos. 54-3083 and 54-27590 show that N-chloromethyl-N-phenylcarbamoyl chloride (II) is too reactive and unstable to handle. It is very inconvenient to use phosgene, which is extremely uncomfortable and extremely toxic in synthesizing isomers. Moreover, when substituents react with different asymmetric thioureas, a large amount of isomers are produced during the cyclization process, making the yield and process difficult. It is disadvantageous in that the yield and purity of the product are lowered because it undergoes a complicated economic process such as recrystallization after extraction and concentration with a solvent different from the solvent.

In addition, the preparation method disclosed in Korean Patent Application Publication No. 91-5747 prevents the use of toxic phosgene, which has been pointed out as a problem in the method of the Japanese patent, and is represented by p-nitromethyl N-chloromethyl N'- After synthesis of phenylcarbamate, the target compound (I) can be prepared, but the product is yellow in color due to impurities, and its purity is poor.

In addition, all of the above patents do not describe the purity of the target compound, so the inventors prepared the target compound by the method described in the above patents to confirm the purity, the purity was as low as 95% or less, In order to improve the purity, more amount was required than the amount of solvent described in the patent, and a problem occurred that the recrystallization yield was significantly lowered. Moreover, Republic of Korea Patent No. 91-5747 tried to remove the yellow phase through crystallization because the target compound had a yellow phase due to the reaction impurity, which degraded the product properties. The solvent described in the phase could not completely remove the yellow phase of the product.

As a result of extensive research to solve this problem, the inventors have found that the target compound has a significant influence on the purity and yield of the product depending on the recrystallized solvent, and the present invention has been completed based on the above finding.

Accordingly, an object of the present invention is to provide an improved method for purifying the target compound (I) capable of economically purifying the target compound (I) in high yield under industrially easy conditions after selecting an optimal recrystallization solvent. To provide.

The method of the present invention for achieving the above object is a high-purity 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1, 3, 5-thiadiazine- represented by the following structural formula (I): In the method for producing 4-one, acetonitrile or a mixed solvent of acetonitrile and water is used for low purity 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1, 3, 5-thiadiazine. Dissolve the 4-one and recrystallize / filter the solution, wash with dilute inorganic acid solution, and then wet 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1, 3, 5 -Thiadiazin-4-one.

Hereinafter, the method of the present invention will be described in more detail.

The present invention provides 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one represented by the above structural formula (I) prepared by a conventional method. To increase the purity and yield of the and to remove the coloring by impurities.

Therefore, in the present invention, the low purity 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1, 3, 5-thiadiazin-4-one, represented by the above structural formula (I), is highly purified. To purify with 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one, methanol, ethanol, acetonitrile, benzene, isopropyl alcohol , Hexane ethyl acetate, ether, water and mixed solvents of these solvents were selected as recrystallization solvents. Among them, acetonitrile was most preferred as the recrystallization solvent, and acetonitrile and water mixed solvents also showed excellent results. Coloring by was also the least.

The acetonitrile is used 2.0 to 4.0 parts by weight based on 1 part by weight of the target compound (I), but the desired purity cannot be obtained outside the above range. In addition, in order to completely remove the color of the target compound (I) that has been refined through recrystallization, the yield tends to decrease when sufficient washing with a large amount of recrystallization solvent or the crystallization process is performed outside the temperature range of -10 to 10 ° C. .

In the present invention, when a mixed solvent of acetonitrile and water is used as the recrystallization solvent, it is preferable to mix water at 0.3 parts by weight or less with respect to 1 part by weight of acetonitrile, and when the mixed amount of water exceeds 0.3 parts by weight, the purity tends to decrease. There is this. Such a mixed solvent is also used in an amount of 2.0 to 4.0 parts by weight based on 1 part by weight of the target compound (I).

0.1-5% by weight of inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid were added to the target compound (I) obtained through this recrystallization process, and then heated to 40-80 ° C and stirred for 10-30 minutes in order to effectively remove color. Thereafter, the mixture was filtered at the above temperature, washed with water to obtain a wet compound, and dried to obtain a target compound (I) having a purity of 98% or more and a purification yield of 85% or more.

In addition, the same result was obtained even if the spent purification solvent and acid wastewater generated in the filtration process were reused as a reaction solvent for the next reaction without undergoing separate purification.

Hereinafter, the method and effect of the present invention will be described in more detail with reference to comparative examples and examples, but the scope of the present invention is not limited to the following examples.

Comparative Example 1

It carried out by the method of Unexamined-Japanese-Patent No. 54-3083 and 54-27590. In a mixture of 100 ml of acetone and 200 ml of dimethylformamide, 42.0 g (0.2 mol) of N-chloromethyl-N-phenylcarbamoyl chloride and 34.0 g (0.2 mol) of 1-isopropyl-3-t-butylthiourea were added. 80 ml of 30% (W / W) aqueous potassium hydroxide solution was added while stirring the solution at room temperature, and the mixture was further stirred for 4 hours. The reaction mixture was poured into water and extracted with 2000 ml of benzene. The benzene layer was washed with water, dried and concentrated to give 62.0 g (purity: 85.1%) of yellowish, low purity target compound (I). 67 ml of isopropyl alcohol was poured into the mixture, warmed to 50 ° C, dissolved, and cooled to 0 ° C. The precipitated pale yellow target compound was filtered and dried to obtain 12.0 g of the target compound (I) having a purity of 92.4% and a yield of 65.2%.

Comparative Example 2

Experiment with the manufacturing method disclosed in Korean Patent Publication No. 91-5747.

117.0 g of p-nitrophenyl N- [N'-t-butyl N ''-isopropyl-isothiourade] methyl N-phenylcarbamate was dissolved in 130 ml of acetonitrile, and then 107 g of calcium hydroxide was added thereto, followed by 24 at room temperature. After stirring for a period of time, the solvent was removed from the acetonitrile solution to obtain 86.0 g of a low purity target compound (I) with a purity of 86.2%. Of which 20.0 g was taken, 60 ml of isopropyl alcohol was poured and warmed to 50 ° C to dissolve. After cooling to 0 ° C., the precipitated pale yellow target compound was filtered and dried to obtain a purity of 93.3% and a yield of 59.4%.

Example 1

Take 20.0 g of the yellow low-purity target compound (I) prepared in Comparative Example 1, add 60 ml of acetonitrile, dissolve by heating to 50 ° C, cool to 0 ° C, stir for 30 minutes, and then precipitate the pale yellow color. Filtration of compound (I) was added to 60 ml of 1.0% by weight hydrochloric acid solution, warmed to 60 ° C, stirred for 30 minutes, filtered at the temperature, washed with 40 g of water, and dried to give the white desired compound (I) as yellow. The target compound was filtered and dried to obtain 12.0 g of the target compound (I) with a purity of 92.4% and a yield of 65.2%.

Purity analysis was performed in Comparative Example 1 and the following Examples and Comparative Examples using quantitative analysis of the pesticide analysis method issued by the National Institute of Agricultural Science and Technology using chromatography (G / C) as follows.

0.5 g of a standard product (CHEM SERVICE, purity 99.9%) of the compound represented by the above formula (I) was placed in a 25 ml flask, dissolved in ethyl acetate, and the solution was dissolved in 1, 2, 3, 4 and 5 ml, respectively. Take 50 ml revolving triangle flask, add 10 ml of internal standard solution (0.9%, triphenylmethane in ethyl acetate), and adjust the final volume to 30 ml with ethyl acetate. 24 μl of each of these solutions is injected into G / C to prepare a quantitative calibration curve.

I. Preparation of Sample Solution

Place 0.06 g of the target compound in a 50 ml revolving triangle flask, add 10 ml of internal standard solution, adjust the final volume by 30 ml with ethyl acetate, place in an ultrasonic container for about 10 minutes, and place 20 μl of the supernatant in G / C. It is injected into and the area ratio of a compound is obtained.

All. Analysis condition

-Column: Filling 2% Silicone SE-30 / Chromomosorb W.AW DMCS (60/80) ID 3mm × 1m

Temperature: Oven 210 ℃, Injector 240 ℃, Detector 240 ℃

Gas flow rate: He 60ml / min, H ₂ 30ml / mim, Air 300ml / min

Injection volume: 2 μl

la. Purity Formula

Comparative Example 2

Experiment with the manufacturing method disclosed in Korean Patent Publication No. 91-5747.

After dissolving 117.0 g of p-nitrophenyl N- (N'-t-butyl N ''-isopropyl-isothiourade) methyl N-phenylcarbaate in 130 ml of acetonitrile, 107 g of calcium hydroxide was added thereto and at room temperature for 24 hours. After stirring and filtration to remove the solvent from the acetonitrile solution, 86.0 g of low purity target compound (I) was obtained with a purity of 86.2%, of which 20.0 g was taken, 60 ml of isopropyl alcohol was poured and heated to 50 ° C to dissolve. The slightly yellow target compound precipitated by cooling to 0 ° C. was filtered and dried to obtain a purity of 93.3% and a yield of 59.4%.

Example 1

Take 20.0 g of the yellow low purity target compound (I) prepared in Comparative Example 1, add 60 ml of acetonitrile, dissolve by heating to 50 ° C., cool to 0 ° C., stir for 30 minutes, and then precipitated pale yellow. The target compound (I) was filtered, 60 ml of 1.0% hydrochloric acid solution was added, heated to 60 ° C., stirred for 30 minutes, filtered at the temperature, washed with 40 g of water, and dried to give a white target compound (I) of purity 98.5 14.8g was obtained by the yield of 85.6%.

Example 2

20.0 g of the yellow low-purity target compound (I) prepared in Comparative Example 2 was crystallized by the recrystallization method of Example 1, washed with 60 ml of 1.0 wt% hydrochloric acid solution, and dried to obtain a purity of 98.7% powder. Compound (I) was obtained in a yield of 86.3%.

Example 3

Take 20.0 g of the low-purity target compound (I) prepared in Comparative Example 1, add 80 ml of acetonitrile, dissolve by heating to 50 ° C., add 10 ml of water, cool to 0 ° C., and stir for 30 minutes. The target compound (I) was filtered, washed with 60 ml of 5% by weight sulfuric acid solution, and dried to obtain 15.3 g (yield: 88.6%) of the target compound (I) having a purity of 98.6%.

Example 4

Take 20.0 g of the low-purity target compound (I) prepared in Comparative Example 2, crystallize by the method of Example 1, wash with 60 ml of 2% by weight sulfuric acid solution, and dry to obtain a target compound (I) having a purity of 98.3%. 15.3g (yield: 87.2%) was obtained.

Example 5

55.2 g (purity: 85.5%) of low purity target compound (I) was prepared by reusing the solvent recovered in Example 2 in the same manner as in Comparative Example 2, and then crystallized and washed by the recrystallization method of Example 1 (I) 42.0 g was obtained. The purity was 98.8% and the yield was 87.7%.

Example 6

Take 20.0 g of the low-purity target compound (I) obtained in Comparative Example 2, crystallize by the method of Example 1, wash with 60 ml of 5% by weight phosphoric acid solution, and dry to obtain 98.1% pure target compound (I). 15.3g (yield: 87.1%) was obtained.

Discoloration due to impurities was not observed in the products manufactured and purified by the method described in Examples 1 to 6 even when stored for 6 months. Table 1 compares the results of the preparation according to the present invention with the results of the present invention and the results of the purification according to the present invention.

As can be seen in Table 1, the target compound (I) prepared according to the method of the present invention is superior in purity and yield in terms of purity and yield than the target compound (I) prepared by the methods described in the prior patents.

Claims (4)

In the manufacturing method of the high purity 2-t-butylimino-3-isopropyl-5-phenyl- tetrahydro-1, 3, 5-thiadiazin-4-one represented by the following structural formula (I), low purity 1 part by weight of 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1,3,5-thiadiazin-4-one 2.0 to 4.0 parts by weight of acetonitrile or a mixed solvent of acetonitrile and water Dissolved in water, recrystallized / filtered at a temperature range of -10 to 10 ° C. for 0.5 to 2 hours, washed with dilute inorganic acid solution, and then wet 2-t-butylimino-3-isopropyl-5-phenyl-tetra 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1, 3, 5-thiadia, characterized by drying hydro-1, 3, 5-thiadiazin-4-one High Purity Purification of Jin-4-one. [2] The 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1 according to claim 1, wherein the mixed solvent is used in an amount of 0.1 to 0.3 parts by weight based on 1 part by weight of acetonitrile. 3, 5-Tiadiazin-4-one of high purity purification method. 2. 2-t-butylimino-3-isopropyl-5-phenyl-tetrahydro-1, 3, 5-, characterized in that the inorganic acid is 0.1 to 5% by weight of hydrochloric acid, sulfuric acid or phosphoric acid. Method for purifying high purity of thiadizin-4-one. [2] The 2-t-butylimino-3-isopropyl- according to claim 1, wherein the spent refining solvent and the acid wastewater generated during the filtration and washing are reused as the next reaction solvent without passing through a separate stagnation. A high purity purification method of 5-phenyl-tetrahydro-1, 3, 5-thiadiazin-4-one.