CN110818588B

CN110818588B - Preparation method of pyrazole amide bactericide intermediate ketene oxime compound

Info

Publication number: CN110818588B
Application number: CN201911091568.8A
Authority: CN
Inventors: 吴晓伟; 赵树林; 王徵; 王刚
Original assignee: Nantong Jiangshan Agrochemical & Chemicals Co ltd
Current assignee: Nantong Jiangshan Agrochemical & Chemicals Co ltd
Priority date: 2019-11-10
Filing date: 2019-11-10
Publication date: 2022-07-15
Anticipated expiration: 2039-11-10
Also published as: CN110818588A

Abstract

The invention relates to a preparation method of a pyrazole amide bactericide intermediate ketene oxime compound. The reaction is that the ketene ether compound, organic sodium carboxylate and hydroxylamine hydrochloride are subjected to oximation reaction in a solvent under the condition of 50 ℃ to solvent reflux temperature to obtain the ketene oxime compound. The solvent is preferably aqueous ethyl acetate, tetrahydrofuran or dioxane. The method has mild reaction conditions, simple and convenient post-treatment, high product yield of about 70 percent, high purity of over 95 percent, high byproduct sodium chloride content of 99 percent and good economical efficiency and environmental protection.

Description

Preparation method of pyrazole amide bactericide intermediate ketene oxime compound

Technical Field

The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of a chemical intermediate ketene oxime compound.

Background

The pyrazole amide compounds have certain bactericidal activity, and CN104649973A discloses that pyrazole amide (general formula III) compounds shown as the following reaction products have good bactericidal activity on rice sheath blight disease. The compound is obtained by condensation reaction of ketene oximes (general formula II) and acyl halides (general formula IV), and the quality, content and yield of the ketene oximes determine the quality and cost of the final product of pyrazole amide compounds.

The conventional synthesis process of the ketene oximes adopts a raw material ketene ether compound as a raw material and methanol as a solvent, but the ketene ether compound (shown in a general formula I) has an intra-ring double bond, carbonyl and ether structure, so that the isomerization and rearrangement are easy to generate the cyclic lactam impurity in the process of synthesizing the ketene oximes, and the yield is only about 50 percent.

。

So far, the technical personnel are dedicated to continuously research and develop advanced and reasonable preparation methods so as to obtain bactericides with better quality and lower cost.

Application No.: 2019104901391 discloses a synthesis method of 16-methyl-2, 6, 6, 8-tetramethyl tricyclo-8-alkenoxime-O- (4-chlorobenzyl) ether, belonging to the technical field of organic compound synthesis. The method comprises the steps of taking methyl cedarwood ketoxime and 4-chlorobenzyl chloride as raw materials, tetrabutylammonium bromide as a phase transfer catalyst, an organic solvent as a reaction solvent, stirring at a constant temperature under an alkaline condition for reaction, and washing and purifying a target product after the reaction is finished. The 16-methyl-2, 6, 6, 8-tetramethyl tricyclo-8-alkenoxime-O- (4-chlorobenzyl) ether is a new compound, is a typical oxime ether derivative, and has good application prospect in the preparation of pesticides, insecticides or bactericides. In the synthesis method, tetrabutylammonium bromide is used as a phase transfer catalyst, and the catalyst is troublesome to separate, so that the purity of the finished product is influenced.

Application No.: 2017112183469 discloses a compound composition containing isolongifolene ketoxime lactam and fluopicolide and a preparation. The composition consists of isolongifolenone oxime lactam and fluopicolide, wherein the weight ratio of the isolongifolenone oxime lactam to the fluopicolide is (40-1): (1 to 40), more preferably (10 to 1) and (1 to 10). The invention is only a pesticide compounding technology, and cannot be used for reference in synthesizing pesticide intermediates.

Disclosure of Invention

The invention aims to:

aims to provide a preparation method of a pyrazole amide bactericide intermediate ketene oxime compound with higher product yield, higher purity and lower cost.

In order to achieve the purpose, the invention adopts the technical scheme that:

a preparation method of ketene oximes comprises the following steps of carrying out oximation reaction on a ketene ether compound, organic carboxylic acid sodium salt and hydroxylamine hydrochloride in a solvent to obtain the ketene oximes as shown in the following reaction formula:

the equation is as follows:

；

in the formula:

r1 is selected from hydrogen, methyl or ethyl;

r2 is selected from methyl, ethyl, propyl or isopropyl;

r3 is selected from hydrogen, methyl or ethyl;

the oximation reaction temperature is controlled to be 50-100 ℃ (or within the solvent reflux temperature range); the oximation reaction time is 0.5-8 hours; the molar ratio of the general formula I to the sodium carboxylate and the hydroxylamine hydrochloride is 1:0.8:0.8-1:1.8: 1.8.

The solvent is selected from dichloromethane, dichloroethane, chloroform, carbon tetrachloride, pentane, hexane, octane, benzene, toluene, xylene, methyl acetate, ethyl acetate, propyl acetate, acetonitrile, butyronitrile, diethyl ether, tetrahydrofuran, dioxane, acetone, butanone, methyl propyl ketone, methyl isopropyl ketone, methyl butyl ketone, methyl isobutyl ketone and ethyl isobutyl ketone.

The solvent is selected from ethyl acetate, tetrahydrofuran or dioxane. Preferred solvents are aqueous ethyl acetate, tetrahydrofuran and dioxane.

General formula (VII)

The normal preparation method is that under the anhydrous condition, anhydrous organic pure organic solvent is used as solvent, raw material ketene, hydroxylamine hydrochloride and sodium carboxylate (preferably sodium acetate) react to synthesize an oximation product, and the highest yield is close to 60%.

The preferable preparation method of the invention changes water and organic solvent as solvent, and has the following functions: in hydrous ethyl acetate, tetrahydrofuran and dioxane, the yield of the ketene oximes compound shown in the general formula II is higher, and is improved by about 10 percent compared with the original method and reaches about 70 percent, because the selected organic solvent has certain solubility in water or can be mutually dissolved with water, the finished product can be simultaneously dissolved in the organic solvent; water can promote the dissolution of carboxylic acid and sodium chloride, moving the equilibrium of the reaction to the right.

And other organic solvents such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride and the like have low solubility in water, and the product yield is poor.

In particular, the solvent is an aqueous solution of tetrahydrofuran or dioxane at a concentration of 50-70%. Tetrahydrofuran or dioxane can be mutually soluble with water, and has a cyclic structure with 4-5 carbon atoms, so that impurities such as cyclic lactam (four-membered ring, five-membered ring and six-membered cyclic lactam) shown in a general formula III can be prevented from being generated by isomeric rearrangement in the process of synthesizing a general formula II according to the repulsion effect of same ions and same atomic groups. In addition, a proper amount of water assists in sufficiently dissolving the amount required for the carboxylic acid and sodium chloride produced by the synthesis reaction, so that the reaction proceeds smoothly.

In the invention, the reaction yields are greatly different by adopting the temperature (such as high temperature or low temperature) with larger difference and the time with larger difference at the temperature of 25-75 ℃, and the experimental parameters with higher yield can be provided for production by adopting the proper temperature (such as 65-70 ℃) and the time of 3-5 hours. The curve of the reaction temperature as a function of the reaction time can be seen:

high temperature differs from low temperature in yield, with higher temperatures giving higher yields the faster the reaction, and lower temperatures giving lower yields the slower the reaction.

After the reaction is basically finished, the solvent is removed as soon as possible by adopting the negative pressure condition of about-0.09 MPa and reducing the temperature to be lower (40-50 ℃, the excessive reaction is avoided, side reaction impurities are generated), and the treatment efficiency is improved.

Has the advantages that:

in the preparation process, 2-methyl-3-penta-2-oxycyclohexa-2-enone reacts with sodium acetate and hydroxylamine hydrochloride to obtain 2-methyl-3- (penta-2-oxycyclohexa-2-enone oxime, the reaction conditions are mild, the post-treatment is simple and convenient, the selected aqueous organic solvent enables the product yield to reach about 70%, the purity to reach more than 95%, the negative pressure desolventization is rapid, the content of the byproduct sodium chloride after the desolventization reaches 99%, and the recycling and use can reduce the cost. The solvent is tetrahydrofuran or dioxane containing water, so that the yield can be improved, the generation of organic impurities can be reduced, the toxicity is low, and the environmental pollution is reduced.

Description of the attached tables:

table 1 temperature vs product yield in the reaction of the invention:

。

table 2 graph of temperature versus time required for the reaction in the present invention:

。

Detailed Description

The following examples serve to further illustrate the invention.

Example 1:

ethyl acetate was used as solvent, 2-methyl-3-pent-2-oxycyclohex-2-enone (19.6 g, 0.1 mol) was added to a reaction flask, and then anhydrous sodium acetate (9.1 g, 0.11 mol), hydroxylamine hydrochloride (7.6 g, 0.11 mol) and a certain amount of process water were added in sequence. The whole system is heated to about 77 ℃ and the reaction is completed after 4 hours. Filtering, washing the sodium salt filter cake with ethyl acetate, mixing the washing filtrate with the reaction solution, and desolventizing under the condition of-0.09 MPa. When the temperature of the desolventizing system reaches 110 ℃, the temperature is reduced to 50 ℃, methanol which is 5 times of the weight of oily substances in the three-neck flask is added, the temperature is raised to reflux, process water which is 4.5 times of the weight of the oily substances is added after the reflux temperature is reached, the temperature is reduced to room temperature, 15.6 g of oxime compound is obtained by filtration, the content is 95.1%, and the yield is 70.4%.

Example 2:

tetrahydrofuran was used as solvent, 2-methyl-3-pent-2-oxycyclohex-2-enone (19.6 g, 0.1 mol) was added to a reaction flask, followed by anhydrous sodium acetate (9.1 g, 0.11 mol), hydroxylamine hydrochloride (7.6 g, 0.11 mol) and a quantity of process water. The whole system is heated to about 70 ℃, and the reaction is finished after 4 hours. Filtering, washing the sodium salt filter cake with tetrahydrofuran, and mixing the washing filtrate with the reaction solution to exsolution under the condition of-0.09 MPa. When the temperature of the desolventizing system reaches 110 ℃, the temperature is reduced to 50 ℃, methanol which is 5 times of the weight of oily substances in the three-neck flask is added, the temperature is raised to reflux, process water which is 4.5 times of the weight of the oily substances is added after the reflux temperature is reached, the temperature is reduced to room temperature, 15.9 g of oxime compound is obtained by filtration, the content is 95.5%, and the yield is 72.1%.

Example 3:

using dioxane as solvent, 2-methyl-3-pent-2-oxycyclohex-2-enone (19.6 g, 0.1 mol) was added to a reaction flask, followed by anhydrous sodium propionate (10.5 g, 0.11 mol), hydroxylamine hydrochloride (7.6 g, 0.11 mol) and a quantity of process water. The whole system is heated to about 80 ℃, and the reaction is finished after 4 hours of reflux. Filtering, washing the sodium salt filter cake by dioxane, and mixing the washing filtrate with the reaction liquid for desolventizing under the condition of-0.09 MPa. When the temperature of the desolventizing system reaches 110 ℃, the temperature is reduced to 50 ℃, methanol which is 5 times of the weight of oily matters in the three-neck flask is added, the temperature is raised to reflux, process water which is 4.5 times of the weight of the oily matters is added after the reflux temperature is reached, the temperature is reduced to room temperature, 15.6 g of oxime compound is obtained by filtration, the content is 96.2%, and the yield is 71.4%.

Claims

1. A preparation method of a pyrazole amide bactericide intermediate ketene oxime compound is characterized by comprising the following steps: an ketene ether compound, organic carboxylic acid sodium salt and hydroxylamine hydrochloride are subjected to oximation reaction in a solvent to obtain an ketene oxime compound, wherein the oximation reaction is shown in the following reaction formula:

；

in the formula:

r1 is selected from methyl or ethyl;

r2 is selected from methyl, ethyl, propyl or isopropyl;

r3 is selected from methyl or ethyl;

is shown as a general formula I;

the temperature of the oximation reaction is controlled to be 50-100 ℃, and the temperature is in the range of the reflux temperature of the solvent; the oximation reaction time is 4-5 hours; the mol ratio of the general formula I to the sodium carboxylate and the hydroxylamine hydrochloride is 1:0.8-1.8: 0.8-1.8;

the solvent is tetrahydrofuran or dioxane water solution with the concentration of 50-70%;

after the reaction is basically finished, the solvent is removed completely by adopting the negative pressure condition of about-0.09 MPa and the temperature reduced to 40-50 ℃.

2. The process for producing a pyrazole amide fungicide intermediate, an enone oxime compound according to claim 1, characterized in that: the solvent is tetrahydrofuran or dioxane water solution with concentration of 50%.

3. The process for producing a pyrazole amide fungicide intermediate enone oxime compound according to claim 1 or 2, characterized in that: the oximation reaction temperature is controlled to be 65-70 ℃; the oximation reaction time is not less than 4 hours.