CN106928253A - A kind of preparation method of pinoxaden - Google Patents

Abstract

The present invention relates to a preparation method of pinoxaden, the steps are as follows: 2,6-diethyl-4-methylaniline is reacted with sandmeyer to obtain 2,6-diethyl-4-methylbromobenzene, and then mixed with Malononitrile is coupled under the catalysis of cuprous iodide to obtain 2,6-di-ethyl-4-methylphenylmalononitrile, and finally hydrolyzed in hydrogen peroxide solution to obtain 2,6-diethyl-4 ‑Methylphenylmalonamide; subsequent reaction with [1,4,5]‑oxadiazepine dihydrobromide in the presence of triethylamine to give 8‑(2,6‑diethyl‑ 4-methylbenzene)tetrahydropyrazol[1,2d][1,4,5]-oxadiazepine-7,9-dione, preferably reacted with pivaloyl chloride to obtain pinoxaden. The invention adopts a low-priced catalyst to reduce the production cost, and in addition, hydrogen peroxide-alkali is used as the hydrolysis system in the preparation process, which greatly reduces environmental pollution.

Description

A kind of preparation method of pinoxaden

technical field

The invention belongs to the field of preparation of technical compounds, and in particular relates to a preparation method of pinoxaden.

Background technique

Pinoxaden chemical name: 8-(2,6-diethyl-4-methylphenyl)-l,2,4,5-tetrahydro-7-oxo-7H-pyrazol[1 ,2-d][1,4,5]Oxadiazepine-9-yl 2,2-dimethylpropionate, the chemical structure is:

Pinoxaden is a new phenylpyrazoline herbicide developed by Syngenta Crop Protection Co., Ltd. in Switzerland. It is an acetyl-CoA carboxylase (ACC) inhibitor herbicide. The leaf absorbs it, and then conducts it to the meristem, causing fatty acid synthesis to be blocked, cell division to stop, cell membrane lipid-containing structure to be destroyed, and weeds to die. This variety is systemic and fast-acting. Generally, sensitive weeds stop growing within 48 hours after application, the weed leaves start to turn yellow within 1-2 weeks, and the weeds completely die within 3-4 weeks. The response speed of weed damage after pesticide application is related to climatic conditions, weed species, growth conditions and so on. The drug is highly safe to barley. When the drug is applied under adverse climatic conditions (low temperature or high humidity), barley leaves may appear temporary chlorosis symptoms, but it will not affect its normal growth and final yield. In addition, the drug degrades quickly in the soil, is rarely absorbed by the roots, has only very low soil activity, has no effect on subsequent crops, is resistant to rain erosion, and hardly affects the weeding effect when it rains for one hour after application.

At present, there are mainly two synthetic routes for pinoxaden, route one is [1,4,5]-oxadiazepine dihydrobromide and 2-(2,6-diethyl-4 -Methylbenzene) malonamide reacts to generate 8-(2,6-diethyl-4-methylbenzene)tetrahydropyrazol[1,2d][1,4,5]-oxadiazepine -7,9-dione, then react with pivaloyl chloride to obtain pinoxaden, the reaction process is as follows:

Another route is the reaction of [1,4,5]-oxadiazepine dihydrobromide with 2-(2,6-diethyl-4-methylbenzene) ethyl malonate to form 8- (2,6-Diethyl-4-methylbenzene)tetrahydropyrazol[1,2d][1,4,5]-oxadiazepine-7,9-dione, and neopentyl The acid chloride reaction obtains the target product, and the approximate process path is as follows:

Although this synthetic patent method can achieve the purpose of synthesizing pinoxaden, it is difficult to prepare 2-(2,6-diethyl-4-methylbenzene) malonamide or 2-(2,6-diethyl The weak point that exists in the process of -4-methylbenzene) ethyl malonate is: (1) 2,6-diethyl-4-methylbromobenzene and malononitrile or diethyl malonate Used expensive bistriphenylphosphine palladium chloride as catalyst in the reaction process, the cost is too high for industrialized production; (2) 2-(2,6-diethyl-4-methylbenzene) malononitrile The preparation of 2-(2,6-diethyl-4-methylbenzene) malonamide by hydrolysis of concentrated sulfuric acid produces a large amount of sulfuric acid wastewater and the environment is under great pressure.

Contents of the invention

The technical problem to be solved by the present invention is to provide a low-cost, environmentally friendly method for preparing pinoxaden, which is used in the preparation of 2-(2,6-diethyl-4-methyl phenyl)malonamide or ethyl 2-(2,6-diethyl-4-methylbenzene)malonate using inexpensive cuprous iodide, cuprous bromide or bistriphenyl Phosphine nickel chloride is used as a catalyst to replace traditional bistriphenylphosphine palladium chloride to reduce costs; in the process of preparing 2-(2,6-diethyl-4-methylbenzene) malonamide, using Hydrogen peroxide and alkali hydrolysis replace concentrated sulfuric acid hydrolysis to reduce the generation of waste sulfuric acid, which is beneficial to environmental protection and improves the safety of production.

In order to solve the problems of the technologies described above, the technical solution provided by the invention is:

Provide a kind of preparation method of pinoxaden, it comprises the following steps:

Step 1): first compound shown in formula I

2,6-diethyl-4-methylbromobenzene represented by formula II is produced by diazotization and thermal decomposition of sodium nitrite

Step 2): 2,6-diethyl-4-methylbromobenzene shown in formula II is reacted with malononitrile or diethyl malonate under the action of a catalyst, and the catalyst is cuprous iodide , cuprous bromide or bistriphenylphosphine nickel chloride, correspondingly generate 2-(2,6-diethyl-4-methylbenzene) malononitrile shown in formula III or formula IV Diethyl 2-(2,6-diethyl-4-methylbenzene)malonate

Then the compound shown in formula III is hydrolyzed by hydrogen oxide-alkali system to generate 2-(2,6-diethyl-4-methylbenzene) malonamide shown in formula V

Step 3): Then react the compound shown in formula IV or V with [1,4,5]-oxadiazepine hydrogen bromide salt to generate 8-(2,6-diethyl- 4-Methylbenzene)tetrahydropyrazol[1,2d][1,4,5]-oxadiazepine-7,9-dione

Step 4): Finally, the compound shown in formula VI is reacted with pivaloyl chloride to generate the compound shown in formula VII

The compound represented by formula VII is pinoxaden.

According to the above-mentioned scheme, step 1) the process conditions for generating 2,6-diethyl-4-methylbromobenzene shown in formula II through sodium nitrite diazotization thermal decomposition of the compound shown in formula I are as follows: Add the compound 2,6-diethyl-4-methylaniline and hydrobromic acid solution shown in I into the reaction flask, add sodium nitrite aqueous solution dropwise at a temperature of -5-0°C to react for 1-5 hours, and then heat up React at 60-90°C for 1-4h. After the reaction, pour the reaction solution into ice water, extract with dichloromethane, concentrate, and distill under reduced pressure to collect the fraction at 102-106°C/5mmHg to obtain formula II 2,6-Diethyl-4-methylbromobenzene.

In the process of the diazotization and decomposition of the compound shown in I shown in the compound shown in II, sodium nitrite is used as the diazotization reagent, and hydrobromic acid is used as the reaction meson. The compound shown in I, 2,6-diethyl- The molar ratio of 4-methylaniline to sodium nitrite and hydrogen bromide is 1:1.0～1.5:1.0～6.0.

According to the above-mentioned scheme, step 2) described 2,6-diethyl-4-methylbromobenzene shown in formula II is reacted with malononitrile or diethyl malonate under the action of a catalyst and the process conditions are: Add 2,6-diethyl-4-methylbromobenzene, malononitrile or diethyl malonate, alkali, catalyst, and solvent shown in formula II into the reaction flask, and react at 30-130°C for 5-20h , and then remove the solvent under negative pressure -0.095MPa, 90°C, then add 8-10 times of water, extract with ethyl acetate, and concentrate to obtain 2-(2,6-diethyl-4-methanol as shown in formula III phenyl) malononitrile or 2-(2,6-diethyl-4-methylbenzene) diethyl malonate shown in formula IV. Yield 60-78%. Melting point: 82-85°C.

Preferably, the molar ratio of 2,6-diethyl-4-methylbromobenzene, malononitrile and base is 1:1-1.5:1.0-6.0.

According to the scheme, the alkali is any one of sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide and sodium hydride.

According to the above scheme, the solvent is any one of xylene, N-methylpyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide, toluene, tetrahydrofuran; the amount of the catalyst is the mole of the compound of formula II 3-5% of the volume. Preferably, the solvent is dimethylsulfoxide or N-methylpyrrolidone.

Step 2) The process conditions for generating 2-(2,6-diethyl-4-methylbenzene) malonamide shown in formula V by hydrolyzing the compound shown in formula III through hydrogen oxide-alkali system are as follows: Compound 2-(2,6-diethyl-4-methylbenzene) malononitrile shown in III, 5wt% sodium hydroxide aqueous solution and 30wt% hydrogen peroxide are added in the reaction flask, and the Reacted for 2-10h, then cooled to room temperature, and then neutralized with hydrochloric acid, a large amount of white solid was precipitated, filtered, washed with water, and dried to obtain a white solid, namely 2-(2,6-diethyl-4- Methylbenzene) malonamide. Yield 75-82%.

According to the above scheme, the molar ratio of 2-(2,6-diethyl-4-methylbenzene) malononitrile to hydrogen peroxide and sodium hydroxide is 1:3-10:1.0-1.5.

According to the above scheme, in step 3), the compound shown in formula IV or V is reacted with [1,4,5]-oxadiazepine hydrogen bromide salt to generate 8-(2,6- The process condition of diethyl-4-methylbenzene)tetrahydropyrazol[1,2d][1,4,5]-oxadiazepine-7,9-dione is as follows: Compound 2-(2,6-diethyl-4-methylbenzene) malonate or compound 2-(2,6-diethyl-4-methylbenzene) malonamide represented by formula V , [1,4,5]-Oxadiazepine hydrogen bromide salt, triethylamine and xylene were added to the reaction flask, the temperature was raised to 115-120°C, and the reaction was stirred for 2-10h, then cooled and washed with hydrochloric acid Adjust the pH to 3, stir for 20-30 minutes, a yellow solid precipitates, filter, wash the filter cake with water, and dry to obtain a light yellow solid, which is the compound represented by formula VI. The yield is 76-80%, and the melting point is 160-165°C.

According to the above scheme, the molar ratio of the 2-(2,6-diethyl-4-methylbenzene) malonamide to [1,4,5]-oxadiazepine hydrogen bromide salt is 1 :1～1.5.

According to the above scheme, the process conditions for the reaction of the compound shown in the formula VI and pivaloyl chloride in step 4) to generate the compound shown in the formula VII are as follows: the compound 8-(2,6-diethyl-4-methanol) shown in the formula VI phenyl)tetrahydropyrazol[1,2d][1,4,5]-oxadiazepine-7,9-dione, pivaloyl chloride, triethylamine, 4-dimethylaminopyridine and tetrahydrofuran Add it into the reaction bottle, stir the reaction at 20-25°C for 1-10h, then pour the reaction liquid into saturated brine, extract with ethyl acetate, concentrate and crystallize, and wash the obtained solid with n-hexane to obtain an off-white solid, that is, the formula The compound pinoxaden shown in VII. Yield: 80%, melting point: 120-122°C.

The beneficial effect of the present invention is: 1, the present invention changes intermediate 2-(2,6-diethyl-4-methylbenzene) malononitrile and 2-(2 , the preparation method of 6-diethyl-4-methylbenzene) ethyl malonate, in the reaction process of 2,6-diethyl-4-methylbromobenzene and malononitrile or ethyl malonate Among them, using cheap and easy-to-get cuprous iodide, cuprous bromide or bistriphenylphosphine nickel chloride as a catalyst, compared with the use of expensive bistriphenylphosphine palladium chloride in the conventional process, greatly reduces the production 2, the preparation technology of pinoxaden of the present invention is in the preparation process of 2-(2,6-diethyl-4-methylbenzene) malonamide, adopts hydrogen peroxide-alkali to do hydrolysis System, instead of the conventional concentrated sulfuric acid hydrolysis method, reduces the discharge of waste acid in the production process, greatly reduces environmental pollution, and improves production safety.

detailed description

In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be further described in detail below in conjunction with examples.

Example 1

To prepare pinoxaden, the specific steps are as follows:

1. Synthesis of 4-methyl-2,6-diethylbromobenzene

Add 65.2g (0.4mol) of 2,6-diethyl-4-methylaniline to 280g of hydrobromic acid solution with a mass fraction of 40%, cool to 0-5°C, and add sodium nitrite aqueous solution drop by drop (33.1g, 0.48mo1 sodium nitrite dissolved in 100mL water), after dripping, stir for 30min and then add 26.2g (0.2mo1) cuprous bromide, heat to 60°C for 4h, TCL tracking the reaction process, the reaction is over Finally, the mixture was poured into 250 mL of ice water, extracted three times with dichloromethane, then dried with anhydrous sodium sulfate and rotary evaporated, concentrated to obtain 92.36 g of crude product, and the fraction at 102-106 °C/5 mmHg was collected by vacuum distillation to obtain 81.07 g product. Yield 89.2%.

¹ H NMR (CDCl ₃ ) test data: 1.22 (t, 6H); 2.30 (s, 3H); 2.85 (m, 4H); 7.10 (s, 2H).

2. Synthesis of 2-(2,6-diethyl-4-methylbenzene) malononitrile

Add 7.92g (0.12mol) of malononitrile, 16g (0.4mol) of sodium hydroxide, and 100mL of dimethyl sulfoxide into a 250mL four-necked reaction flask equipped with a stirrer, a thermometer, and a condenser tube, and pass through nitrogen protection. Heated to 100-110°C and reacted for 2h. Then add 22.7g (0.1mol) of 2,6-diethyl-4-methylbromobenzene and 1.2g of cuprous iodide, and react at 120-130°C for 10h. Cool, then remove the solvent under negative pressure -0.095MPa, 90°C, then add 200g of water, adjust pH=3 with hydrochloric acid, then extract with 3×80mL ethyl acetate, wash with 3×150mL water, concentrate, add 10mL of n-hexane The alkane was frozen and crystallized, filtered, and washed with n-hexane to obtain 15.7 g of a light yellow solid with a yield of 78.5%.

3. Synthesis of 2-(2,6-diethyl-4-methylbenzene) malonamide

Add 2-(2,6-diethyl-4-methylbenzene) malononitrile 21.2g (0.1mol) in a 250mL four-necked reaction flask equipped with a stirrer, a thermometer and a reflux condenser, 30wt% of 68g (0.6mol) of hydrogen oxide solution and 20g (0.025mol) of 5wt% sodium hydroxide were heated up to 50-60°C for 2 hours, then cooled to room temperature, neutralized with hydrochloric acid, a large amount of white solids precipitated, filtered and washed with water , and dried to obtain 20.3 g of a yellow solid, with a yield of 81.8%.

¹ H NMR (CDCl ₃ ) test data: 4.6(d, 4H, CH2), 6.9(t, 1H), 7.4～7.6(m, 4H, ArH), 8.0(s, 1H, PyH), 8.6(s , 1H, PyH).

4. 8-(2,6-diethyl-4-methylbenzene)tetrahydropyrazol[1,2d][1,4,5]-oxadiazepine-7,9-dione synthesis

Add 30g (0.12mol) 2-(2,6-diethyl-4-methylbenzene) malonamide, 38.1g (0.144mol )[1,4,5]-Oxadiazepine hydrogen bromide salt, 51.3g (0.5mol) of triethylamine and 200mL of xylene, heated to 115-120°C, stirred for 10h, then cooled, Add 200g of water, adjust the pH to 3 with hydrochloric acid, stir for 20-30min, a yellow solid precipitates, filter, wash the filter cake with 2×50mL of water, wash with 2×30mL of n-hexane, dry off-white solid 8.5g, xylene layer It was washed with 2×50 mL of water and concentrated to obtain 1.2 g of a light yellow solid. A total of 9.7 g of the product was obtained, with a yield of 76.3% and a melting point of 160-165°C.

5. Synthesis of pinoxaden

In a 250mL four-necked reaction flask equipped with a stirrer, a thermometer, and a condenser tube, add 31g (0.10mol) of 8-(2,6-diethyl-4-methylbenzene)tetrahydropyrazole[1,2d] [1,4,5]-oxadiazepine-7,9-dione, 15g (0.125mol) pivaloyl chloride, 20.1g (0.2mol) of triethylamine, 0.366g (0.03mol) 4- Dimethylaminopyridine and 200 mL of tetrahydrofuran. Stir the reaction at room temperature 20-25°C for 10 h, then pour the reaction solution into 150 mL of saturated brine, extract with 3×100 mL of ethyl acetate, combine the organic phases, wash with 3×60 mL of water, concentrate, and add 50 mL of n-hexane to the residue Crystallized to obtain 32.1 g of off-white solid, yield 80%, melting point: 120-122°C.

¹ H NMR (CDCl ₃ ) test data: δ1.03(s, 9H), 1.12(t, 6H), 2.29(s, 3H), 2.35-2.63(m, 4H), 3.81-3.90(m, 4H) ), 3.93 (m, 2H), 4.26 (m, 2H), 6.88 (s, 2H).

Example 2

To prepare pinoxaden, the specific steps are as follows:

1. The same method as in Example 1 was used to prepare 4-methyl-2,6-diethylbromobenzene.

2. Synthesis of 2-(2,6-diethyl-4-methylbenzene)diethyl malonate

Add 32.0g (0.2mol) of diethyl malonate, 16g (0.4mol) of sodium hydroxide and 100mL of N-methylpyrrolidone into a 250mL four-necked reaction flask equipped with a stirrer, a thermometer, and a condenser. Pass nitrogen protection, heat to 100-110°C, and react for 2 hours. Then add 22.7g (0.1mol) of 2,6-diethyl-4-methylbromobenzene and 1.2g of cuprous bromide, and react at 120-130°C for 10h. Cool, then remove the solvent under negative pressure -0.095MPa, 90°C, add 200g of water, adjust pH=3 with hydrochloric acid, extract with 3×80mL ethyl acetate, wash with 3×150mL water, concentrate, add 10mL n-hexane to freeze Crystallized, filtered, and washed with n-hexane to obtain 22.9 g of light yellow solid with a yield of 75%.

3. Synthesis of 2-(2,6-diethyl-4-methylbenzene) malononitrile

Add 13.2g (0.2mol) of malononitrile, 6.0g (0.2mol) of 80wt% sodium hydride and 100mL of N-methylpyrrolidone into a 250mL four-necked reaction flask equipped with a stirrer, a thermometer and a condenser. Pass nitrogen protection, heat to 100-110°C, and react for 2 hours. Then add 22.7g (0.1mol) of 2,6-diethyl-4-methylbromobenzene and 1.5g of bistriphenylphosphine nickel chloride, and react at 120-130°C for 10h. Cool, add 200g of water, adjust pH to 3 with hydrochloric acid, extract with 3×80mL ethyl acetate, wash with 3×150mL water, concentrate, add 10mL n-hexane to freeze and crystallize, filter, wash with n-hexane to obtain 16.8g of light yellow solid , yield 79.2%.

4. Synthesis of 2-(2,6-diethyl-4-methylbenzene) malonamide

Add 2-(2,6-diethyl-4-methylbenzene) malononitrile 21.2g (0.1mol) in a 250mL four-necked reaction flask equipped with a stirrer, a thermometer and a reflux condenser, 30% over 45g (0.4mol) of hydrogen oxide and 28.0g (0.025mol) of 5wt% potassium hydroxide were heated up to 50-60°C for 4 hours. After cooling to room temperature and neutralizing with hydrochloric acid, a large amount of white solids precipitated, filtered, washed with water, and dried to obtain 19.6 g of white solids and 19.6 g of yellow solids, with a yield of 79%.

5. The compound 8-(2,6-diethyl-4-methylbenzene)tetrahydropyrazol[1,2d][1,4,5]- Oxadiazepine-7,9-dione and the compound pinoxaden represented by formula VII.

Claims (9)

1. a kind of preparation method of pinoxaden, it is characterised in that it is comprised the following steps：

Step 1)：First by compound shown in formula I

The methyl bromobenzene of 2,6- diethyl -4- shown in formula II is thermally decomposed to generate through natrium nitrosum diazotising

Step 2)：Again by the methyl bromobenzene of 2,6- diethyl -4- shown in formula II in the presence of catalyst with malononitrile or malonic acid Diethylester reacts, and the catalyst is the one kind in cuprous iodide, cuprous bromide or bi triphenyl phosphine nickel chloride, is correspondingly generated 2- (2,6- diethyl -4- methylbenzenes) shown in (2,6- diethyl -4- methylbenzenes) malononitrile of 2- shown in formula III or formula IV the third two Diethyl phthalate

Again by compound shown in formula III through hydrogen peroxide -2- (2,6- diethyl -4- methyl shown in alkali systems hydrolysis production V Benzene) malonamide

Step 3)：Formula IV or compound shown in formula V are reacted into production VI with [1,4,5]-oxa- diazepine hydrogen bromide salt again Shown 8- (2,6- diethyl -4- methylbenzenes) tetrahydro-pyrazole [1,2d] [1,4,5]-oxa- diazepine -7,9- diketone

Step 4)：Finally by compound shown in formula VI and compound shown in pivalyl chloride reaction production VII

Compound shown in formula VII is pinoxaden.

2. preparation method according to claim 1, it is characterised in that step 1) it is described by compound shown in formula I through nitrous acid The process conditions that sodium diazotising thermally decomposes to generate the methyl bromobenzene of 2,6- diethyl -4- shown in formula II are：By compound 2 shown in formula I, 6- diethyl -4- methylanilines, hydrobromic acid solution are added in reaction bulb, and natrium nitrosum water is added dropwise under the conditions of being -5-0 DEG C in temperature Solution reaction 1-5h, reacts 1-4h under the conditions of then heating to 60-90 DEG C, reaction is poured into frozen water reaction solution after terminating, and is used Dichloromethane is extracted, and the cut of 102~106 DEG C/5mmHg is collected in concentration, vacuum distillation, that is, obtain 2,6- diethyls shown in formula II Base -4- methyl bromobenzenes.

3. preparation method according to claim 1, it is characterised in that step 2) it is described by 2,6- diethyl -4- shown in formula II The process conditions that methyl bromobenzene reacts in the presence of catalyst with malononitrile or diethyl malonate are：By 2,6- shown in formula II In diethyl -4- methyl bromobenzene, malononitrile or diethyl malonate, alkali, catalyst, solvent addition reaction bulb, at 30-130 DEG C Reaction 5-20h, then removes solvent under the conditions of negative pressure -0.095MPa, 90 DEG C, adds 8-10 times of water, and pH=is adjusted with hydrochloric acid 3, it is extracted with ethyl acetate, it is concentrated to give (2, the 6- diethyl -4- methylbenzenes) malononitrile of 2- shown in formula III or the 2- shown in formula IV (2,6- diethyl -4- methylbenzenes) diethyl malonate.

4. preparation method according to claim 3, it is characterised in that the solvent be dimethylbenzene, 1-METHYLPYRROLIDONE, In N,N-dimethylformamide, dimethyl sulfoxide, toluene, tetrahydrofuran any one；The consumption of the catalyst is the chemical combination of formula II The 3-5% of thing mole.

5. preparation method according to claim 1, it is characterised in that step 2) it is described by compound shown in formula III through peroxide Change hydrogen-process conditions of 2- (2,6- diethyl -4- methylbenzenes) malonamide shown in alkali systems hydrolysis production V as follows：By formula Compound 2- shown in III (2,6- diethyl -4- methylbenzenes) malononitrile, sodium hydrate aqueous solution and aqueous hydrogen peroxide solution are added To in reaction bulb, 2-10h is reacted in 50~60 DEG C, be then cooled to room temperature, then be neutralized with hydrochloric acid, separate out substantial amounts of white solid Body, filtering, washing is dried, and obtains white solid, i.e., 2- (2,6- diethyl -4- methylbenzenes) malonamide shown in formula V.

6. preparation method according to claim 5, it is characterised in that 2- (2, the 6- diethyl -4- methylbenzenes) malononitrile It is 1 with the mol ratio of hydrogen peroxide and NaOH:3~10：1.0~1.5.

7. preparation method according to claim 1, it is characterised in that step 3) it is described by formula IV or compound shown in formula V With 8- (2,6- diethyl -4- methylbenzenes) tetrahydro-pyrazole shown in [1,4,5]-oxa- diazepine hydrogen bromide salt reaction production VI The process conditions of [1,2d] [1,4,5]-oxa- diazepine -7,9- diketone are：By compound 2- (2,6- diethyls shown in formula IV Base -4- methylbenzenes) diethyl malonate or compound 2- shown in formula V (2,6- diethyl -4- methylbenzenes) malonamide, [1,4, 5]-oxa- diazepine hydrogen bromide salt, triethylamine and dimethylbenzene is added in reaction bulb, is warming up to 115-120 DEG C, stirring reaction 2-10h, then cooling, adds water, and pH=3 is adjusted with hydrochloric acid, stirs 20-30min, has yellow solid to separate out, and filters, and filter cake is used Water washing, dry faint yellow solid, i.e., compound shown in formula VI.

8. preparation method according to claim 7, it is characterised in that 2- (2, the 6- diethyl -4- methylbenzenes) malonyl Amine is 1 with the mol ratio of [1,4,5]-oxa- diazepine hydrogen bromide salt:1~1.5.

9. preparation method according to claim 1, it is characterised in that step 4) compound and pivaloyl shown in the formula VI The process conditions of compound are shown in chlorine reaction production VII：By compound 8- shown in formula VI (2,6- diethyl -4- methylbenzenes) Tetrahydro-pyrazole [1,2d] [1,4,5]-oxa- diazepine -7,9- diketone, pivalyl chloride, triethylamine, DMAP and Tetrahydrofuran is added in reaction bulb, and stirring reaction 1-10h, then pours into saturated aqueous common salt reaction solution at 20-25 DEG C, It is extracted with ethyl acetate, condensing crystallizing, gained solid washs to obtain pale solid with n-hexane, that is, obtains compound shown in formula VII Pinoxaden.