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

A kind of preparation method of pinoxaden Download PDF

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CN106928253A
CN106928253A CN201710139204.7A CN201710139204A CN106928253A CN 106928253 A CN106928253 A CN 106928253A CN 201710139204 A CN201710139204 A CN 201710139204A CN 106928253 A CN106928253 A CN 106928253A
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diethyl
formula
methylbenzenes
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刘安昌
董元海
余玉
郑怡倩
汪焱鲁
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Wuhan Institute of Technology
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Wuhan Institute of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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Abstract

The present invention relates to a kind of preparation method of pinoxaden, step is as follows：2, the methylaniline of 6 diethyl 4 obtains 2 by sandmeyer reactions, the methyl bromobenzene of 6 diethyl 4, then coupling obtains 2 under the catalysis such as cuprous iodide with malononitrile, the aminomethyl phenyl malononitrile of 6 diethyl 4, finally the aminomethyl phenyl malonamide of 2,6 diethyl 4 is obtained in hydrogenperoxide steam generator reclaimed water solution；Then 8 (2 are obtained in the presence of triethylamine with the reaction of [Isosorbide-5-Nitrae, 5] oxa- diazepine dihydrobromide, the methylbenzene of 6 diethyl 4) tetrahydro-pyrazole [1,2d] [Isosorbide-5-Nitrae, 5] oxa- diazepine 7,9 diketone preferably obtain pinoxaden with pivalyl chloride reaction.The present invention uses cheap catalyst degradation production cost, makees hydrolyzation system using hydrogen peroxide alkali in preparation process in addition, greatly reduces environmental pollution.

Description

A kind of preparation method of pinoxaden
Technical field
The invention belongs to active compound field of compound preparation, and in particular to a kind of preparation method of pinoxaden.
Background technology
Pinoxaden (Pinoxaden) chemical name：8- (2,6- diethyl -4- aminomethyl phenyls)-l, 2,4,5- tetrahydrochysenes -7- Oxygen -7H- pyrazoles [1,2-d] [Isosorbide-5-Nitrae, 5] oxygen phenodiazine Zhuo -9- base PA esters, chemical structural formula is：
Pinoxaden (Pinoxaden) is the neophyl pyrazolines first just developed up to crop protection Co., Ltd by Switzerland Herbicide, is acetyl-CoA carboxylase (ACC) inhibitor class herbicide, and medicine can be absorbed by grass cutting blade, and then conduction extremely divides Raw tissue, causes aliphatic acid biosynthesis block, stops cell division, and cell membrane is destructurized containing fat, causes weeds dead.Should Kind has an absorbability, work fast, and 48 hours susceptible weeds stop growing after general dispenser, and grass cutting blade is opened in 1~2 week Originate weeds in Huang, 3~4 weeks thoroughly dead.The aggrieved reaction speed of weeds and weather conditions, weeds species, growth after dispenser Condition etc. is relevant.The medicine is safe to barley, (the low temperature or high humidity) dispenser under the conditions of bad climate, and barley leaves may There is temporary transient chlorosis symptom, but do not influence its normal growth to develop and ultimate output.In addition, the medicine is in degraded in soil Hurry up, seldom by root absorption, only very low soil activation, on succession crop without influence, resistance of rainwater washing against, l hours after dispenser Meet rain and have substantially no effect on herbicidal effect.
At present, mainly there are two for the synthetic route of pinoxaden, route one is [Isosorbide-5-Nitrae, 5]-oxa- diazepine two Hydrobromate and 2- (2,6- diethyl -4- methylbenzenes) malonamide reaction generation 8- (2,6- diethyl -4- methylbenzenes) tetrahydrochysene Then pyrazoles [1,2d] [Isosorbide-5-Nitrae, 5]-oxa- diazepine -7,9- diketone obtains pinoxaden with pivalyl chloride reaction, reacts Journey is as follows：
Another route is [1,4,5]-oxa- diazepine dihydrobromide and 2- (2,6- diethyl -4- methylbenzenes) third Two acetoacetic esters reaction generation 8- (2,6- diethyl -4- methylbenzenes) tetrahydro-pyrazole [1,2d] [1,4,5]-oxa- diazepine -7, 9- diketone, then purpose product is obtained with pivalyl chloride reaction, substantially processing route is as follows：
Although it is this synthesis patented method can reach synthesis pinoxaden purpose, prepare 2- (2,6- diethyl- 4- methylbenzenes) weak point that exists during malonamide or 2- (2,6- diethyl -4- methylbenzenes) malonic ester exists In：Expensive double triphens have been used in (1) 2,6- diethyl -4- methyl bromobenzene and malononitrile or diethyl malonate course of reaction Base phosphine palladium bichloride makees catalyst, and cost is too high for industrialized production；(2) 2- (2,6- diethyl -4- methylbenzenes) the third two Nitrile prepares 2- (2,6- diethyl -4- methylbenzenes) malonamide using concentrated sulfuric acid Hydrolyze method, produces substantial amounts of sulfuric acid wastewater containing, environment Pressure is very big.
The content of the invention
The technical problems to be solved by the invention are directed to above shortcomings in the prior art, there is provided it is a kind of it is low into Originally, the method for the preparation pinoxaden of environmental protection, is preparing 2- (2,6- diethyl -4- methylbenzenes) malonamides or 2- (2,6- bis- Ethyl -4- methylbenzenes) cheap cuprous iodide, cuprous bromide or bi triphenyl phosphine chlorine are used during malonic ester It is the traditional dual-triphenylphosphine palladium chloride of catalyst replaced to change nickel, reaches the purpose of reduces cost；Preparing 2- (2,6- diethyls Base -4- methylbenzenes) during malonamide, using hydrogen peroxide and basic hydrolysis, replace concentrated sulfuric acid Hydrolyze method, to reduce Waste Sulfuric Acid Generation be conducive to environmental protection, improve the security of production.
In order to solve the above technical problems, the technical scheme that the present invention is provided is：
A kind of preparation method of pinoxaden is provided, 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 third Diethyl adipate reacts, and the catalyst is the one kind in cuprous iodide, cuprous bromide or bi triphenyl phosphine nickel chloride, correspondingly 2- (2,6- diethyl -4- methylbenzenes) shown in (2,6- diethyl -4- methylbenzenes) malononitrile of 2- shown in production III or formula IV Diethyl malonate
Again by compound shown in formula III through hydrogen peroxide -2- (2,6- diethyl -4- first shown in alkali systems hydrolysis production V Base benzene) malonamide
Step 3)：Formula IV or compound shown in formula V are reacted into generation with [1,4,5]-oxa- diazepine hydrogen bromide salt again 8- shown in formula VI (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.
By such scheme, step 1) described compound shown in formula I is thermally decomposed to generate into the institute of formula II through natrium nitrosum diazotising The process conditions for showing 2,6- diethyl -4- methyl bromobenzenes are：By the methylanilines of compound 2,6- diethyl -4- shown in formula I, hydrogen bromine Acid solution is added in reaction bulb, and sodium nitrite in aqueous solution reaction 1-5h is added dropwise under the conditions of being -5-0 DEG C in temperature, is then heated to 1-4h is reacted under the conditions of 60-90 DEG C, reaction is poured into frozen water reaction solution after terminating, and is extracted with dichloromethane, and concentration, decompression is steamed The cut of 102~106 DEG C/5mmHg of collection is evaporated, that is, obtains the methyl bromobenzene of 2,6- diethyl -4- shown in formula II.
It is described to be attached most importance to natrium nitrosum during shown I compound carries out diazotising and is decomposed into compound shown in II Diazotizing reagent, bromine hydracid is reaction meson, compound 2 shown in I, 6- diethyl -4- methylanilines and natrium nitrosum and hydrogen bromide Mol ratio be 1:1.0~1.5:1.0~6.0.
By such scheme, step 2) it is described by 2 shown in formula II, 6- diethyl -4- methyl bromobenzenes are in the presence of catalyst The process conditions reacted with malononitrile or diethyl malonate are：By the bromobenzene of 2,6- diethyl -4- methyl shown in formula II, malononitrile Or diethyl malonate, alkali, catalyst, solvent add reaction bulb in, 30-130 DEG C react 5-20h, then negative pressure- 0.095MPa, remove solvent under the conditions of 90 DEG C, add 8-10 times of water, be extracted with ethyl acetate, be concentrated to give 2- shown in formula III 2- (2,6- diethyl -4- methylbenzenes) diethyl malonate shown in (2,6- diethyl -4- methylbenzenes) malononitrile or formula IV.Receive Rate 60-78%.Fusing point:82-85℃.
Preferably, the mol ratio of 2, the 6- diethyl -4- methyl bromobenzene, malononitrile and alkali is 1：1~1.5：1.0~ 6.0。
By such scheme, the alkali is any one in sodium carbonate, potassium carbonate, NaOH, potassium hydroxide, sodium hydride.
By such scheme, the solvent be dimethylbenzene, 1-METHYLPYRROLIDONE, DMF, dimethyl sulfoxide, In toluene, tetrahydrofuran any one；The consumption of the catalyst is the 3-5% of the compound mole of formula II.Preferably, institute Solvent is stated for dimethyl sulfoxide or 1-METHYLPYRROLIDONE.
Step 2) it is described by compound shown in formula III through 2- (2,6- bis- shown in hydrogen peroxide-alkali systems hydrolysis production V Ethyl -4- methylbenzenes) malonamide process conditions it is as follows：By compound 2- shown in formula III (2,6- diethyl -4- methylbenzenes) The hydrogen peroxide of malononitrile, the sodium hydrate aqueous solution of 5wt% and 30wt% is added in reaction bulb, and 2- is reacted in 50~60 DEG C 10h, is then cooled to room temperature, then is neutralized with hydrochloric acid, and separates out substantial amounts of white solid, and filtering, washing is dried, and obtains white solid, 2- (2,6- diethyl -4- methylbenzenes) malonamide i.e. shown in formula V.Yield 75-82%.
By such scheme, 2- (2, the 6- diethyl -4- methylbenzenes) malononitrile and hydrogen peroxide and NaOH rub Your proportioning is 1:3~10：1.0~1.5.
By such scheme, step 3) it is described by formula IV or compound shown in formula V and [Isosorbide-5-Nitrae, 5]-oxa- diazepine bromination 8- (2,6- diethyl -4- methylbenzenes) tetrahydro-pyrazole [1,2d] [1,4,5]-oxa- diaza shown in hydrogen salt reaction production VI The process conditions of grass -7,9- diketone are：By (2,6- diethyl -4- methylbenzenes) diethyl malonates of compound 2- shown in formula IV or Compound 2- shown in formula V (2,6- diethyl -4- methylbenzenes) malonamide, [1,4,5]-oxa- diazepine hydrogen bromide salt, three Ethamine and dimethylbenzene are added in reaction bulb, are warming up to 115-120 DEG C, and stirring reaction 2-10h is then cooled down, and is adjusted with hydrochloric acid PH=3, stirs 20-30min, has yellow solid to separate out, and filters, and filter cake washes with water, dry faint yellow solid, the i.e. institute of formula VI Show compound.Yield 76-80%, 160-165 DEG C of fusing point.
By such scheme, 2- (2, the 6- diethyl -4- methylbenzenes) malonamides and [Isosorbide-5-Nitrae, 5]-oxa- diazepine The mol ratio of hydrogen bromide salt is 1:1~1.5.
By such scheme, step 4) compound shown in compound shown in the formula VI and pivalyl chloride reaction production VII Process conditions are：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 are added in reaction bulb, Stirring reaction 1-10h, then pours into saturated aqueous common salt reaction solution at 20-25 DEG C, is extracted with ethyl acetate, condensing crystallizing, Gained solid washs to obtain pale solid with n-hexane, that is, obtain compound pinoxaden shown in formula VII.Yield 80%, fusing point： 120-122℃。
The beneficial effects of the present invention are：1st, the preparation technology route by improving pinoxaden of the invention, changes middle The preparation method of body 2- (2,6- diethyl -4- methylbenzenes) malononitrile and 2- (2,6- diethyl -4- methylbenzenes) malonic ester, In the course of reaction of 2,6- diethyl -4- methyl bromobenzene and malononitrile or malonic ester, using the cheap iodine being easy to get Change is cuprous, and cuprous bromide or bi triphenyl phosphine nickel chloride are catalyst, compared to the bi triphenyl phosphine in common process using costliness Palladium bichloride, greatly reduces the cost of production；2nd, the preparation technology of pinoxaden of the present invention is in 2- (2,6- diethyl -4- Methylbenzene) malonamide preparation process in, hydrolyzation system is made using hydrogen peroxide-alkali, replace conventional concentrated sulfuric acid Hydrolyze method, The discharge of spent acid amount in production process is reduced, environmental pollution is greatly reduced, the security of production is improve.
Specific embodiment
To make those skilled in the art more fully understand technical scheme, the present invention is made with reference to embodiment Describe in further detail.
Embodiment 1
Pinoxaden is prepared, is comprised the following steps that：
1st, the synthesis of 4- methyl -2,6- diethyl bromobenzenes
65.2g (0.4mo1) 2,6- diethyl -4- methylanilines are added to the hydrobromic acid that 280g mass fractions are 40% In solution, 0~5 DEG C is cooled to, sodium nitrite in aqueous solution is dropwise added dropwise, and (33.1g, 0.48mo1 natrium nitrosum are dissolved in 100mL water and obtain To), after dripping off, it is cuprous that stirring 30min is subsequently adding 26.2g (0.2mo1) brominationization, is heated to 60 DEG C of insulation 4h, TCL tracking Reaction process, reaction is poured into 250mL frozen water mixed liquor after terminating, and is extracted 3 times with dichloromethane, then uses anhydrous sodium sulfate Dry and rotate, be concentrated to give crude product 92.36g, vacuum distillation is collected the cut of 102~106 DEG C/5mmHg, obtains 81.07g products. Yield 89.2%.
1H NMR(CDCl3) test data is：1.22 (t, 6H)；2.30 (s, 3H)；2.85 (m, 4H)；7.10 (s, 2H).
2nd, the synthesis of 2- (2,6- diethyl -4- methylbenzenes) malononitrile
Equipped with agitator, thermometer in tetra- mouthfuls of reaction bulbs of 250mL of condenser pipe, adds 7.92g (0.12mol) the third two The dimethyl sulfoxide of nitrile, 16g (0.4mol) NaOH and 100mL, is passed through nitrogen protection, is heated to 100~110 DEG C, reacts 2h. 22.7g (0.1mol) 2,6- diethyl -4- methyl bromobenzene and 1.2g cuprous iodides are subsequently adding, 10h is reacted at 120~130 DEG C. Cooling, then removes solvent under the conditions of negative pressure -0.095MPa, 90 DEG C, adds 200g water, and pH=3 is adjusted with hydrochloric acid, then with 3 × 80mL ethyl acetate is extracted, and is washed with 3 × 150mL, concentration, adds 10mL n-hexane freezing and crystallizings, and filtering is washed with n-hexane Wash, obtain faint yellow solid 15.7g, yield 78.5%.
3rd, the synthesis of 2- (2,6- diethyl -4- methylbenzenes) malonamide
Added equipped with agitator, in tetra- mouthfuls of reaction bulbs of 250mL of thermometer and reflux condensing tube 2- (2,6- diethyl- 4- methylbenzenes) malononitrile 21.2g (0.1mol), the hydrogenperoxide steam generator 68g (0.6mol) and the NaOH of 5wt% of 30wt% 20g (0.025mol), is warming up to 50~60 DEG C of reaction 2h, is then cooled to room temperature, is neutralized with hydrochloric acid, and has substantial amounts of white solid Separate out, filtering, washing is dried, and obtains yellow solid 20.3g, yield 81.8%.
1H NMR(CDCl3) test data is：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).
4th, 8- (2,6- diethyl -4- methylbenzenes) tetrahydro-pyrazole [1,2d] [1,4,5]-oxa- diazepine -7,9- diketone Synthesis
Equipped with agitator, thermometer in tetra- mouthfuls of reaction bulbs of 250mL of condenser pipe, adds 30g (0.12mol) 2- (2,6- Diethyl -4- methylbenzenes) malonamide, 38.1g (0.144mol) [Isosorbide-5-Nitrae, 5]-oxa- diazepine hydrogen bromide salt, 51.3g The triethylamine of (0.5mol) and the dimethylbenzene of 200mL, are warming up to 115-120 DEG C, and stirring reaction 10h, then cooling adds 200g Water, pH=3 is adjusted with hydrochloric acid, stirs 20-30min, has yellow solid to separate out, and is filtered, filter cake 2 × 50mL water washings, with 2 × 30mL n-hexanes are washed, and dry pale solid 8.5g, diformazan benzene layer 2 × 50mL water washings are concentrated to give faint yellow solid 1.2g, there are product 9.7g, yield 76.3%, 160-165 DEG C of fusing point.
5th, the synthesis of pinoxaden
Equipped with agitator, thermometer in tetra- mouthfuls of reaction bulbs of 250mL of condenser pipe, adds 31g (0.10mol) 8- (2,6- Diethyl -4- methylbenzenes) tetrahydro-pyrazole [1,2d] [Isosorbide-5-Nitrae, 5]-oxa- diazepine -7,9- diketone, 15g (0.125mol) new penta Acyl chlorides, the tetrahydrofuran of the triethylamine, 0.366g (0.03mol) DMAPs and 200mL of 20.1g (0.2mol). Stirring reaction 10h at 20-25 DEG C of room temperature, then pours into reaction solution in the saturated aqueous common salt of 150mL, with 3 × 100mL acetic acid second Ester is extracted, and merges organic phase, is washed with 3 × 60mL, concentration, and residual night adds the crystallization of 50mL n-hexanes, obtains pale solid 32.1g, yield 80%, fusing point：120-122℃.
1H NMR(CDCl3) test data is：δ 1.03 (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).
Embodiment 2
Pinoxaden is prepared, is comprised the following steps that：
1st, 4- methyl -2,6- diethyl bromobenzenes are prepared using method same as Example 1.
2nd, the synthesis of 2- (2,6- diethyl -4- methylbenzenes) diethyl malonate
Equipped with agitator, thermometer in tetra- mouthfuls of reaction bulbs of 250mL of condenser pipe, adds 32.0g (0.2mol) malonic acid The 1-METHYLPYRROLIDONE of diethylester, 16g (0.4mol) NaOH and 100mL.Nitrogen protection is passed through, 100~110 are heated to DEG C, react 2h.22.7g (0.1mol) 2,6- diethyl -4- methyl bromobenzene and 1.2g cuprous bromides are subsequently adding, 120~130 DEG C reaction 10h.Cooling, then removes solvent under the conditions of negative pressure -0.095MPa, 90 DEG C, adds 200g water, and pH=is adjusted with hydrochloric acid 3, extracted with 3 × 80mL ethyl acetate, washed with 3 × 150mL, concentration, add 10mL n-hexane freezing and crystallizings, filtering, with just Hexane is washed, and obtains faint yellow solid 22.9g, yield 75%.
3rd, the synthesis of 2- (2,6- diethyl -4- methylbenzenes) malononitrile
Equipped with agitator, thermometer in tetra- mouthfuls of reaction bulbs of 250mL of condenser pipe, adds 13.2g (0.2mol) the third two The 1-METHYLPYRROLIDONE of nitrile, the sodium hydride of 6.0g (0.2mol) 80wt% and 100mL.Nitrogen protection is passed through, it is heated to 100~ 110 DEG C, react 2h.It is subsequently adding 22.7g (0.1mol) 2,6- diethyl -4- methyl bromobenzene and 1.5g bi triphenyl phosphine chlorinations Nickel, 10h is reacted at 120~130 DEG C.Cooling, adds 200g water, and pH=3 is adjusted with hydrochloric acid, is extracted with 3 × 80mL ethyl acetate, uses 3 × 150mL is washed, concentration, adds 10mL n-hexane freezing and crystallizings, and filtering is washed with n-hexane, obtains faint yellow solid 16.8g, Yield 79.2%.
4th, the synthesis of 2- (2,6- diethyl -4- methylbenzenes) malonamide
Added equipped with agitator, in tetra- mouthfuls of reaction bulbs of 250mL of thermometer and reflux condensing tube 2- (2,6- diethyl- 4- methylbenzenes) malononitrile 21.2g (0.1mol), 30% hydrogen peroxide 45g (0.4mol) and the potassium hydroxide 28.0g of 5wt% (0.025mol), is warming up to, 50~60 DEG C of reaction 4h.Room temperature is cooled to, is neutralized with hydrochloric acid, there is substantial amounts of white solid to separate out, Filtering, washing is dried, and is obtained white solid and is obtained yellow solid 19.6g, yield 79%.
5th, using compound 8- shown in method formula VI same as Example 1 (2,6- diethyl -4- methylbenzenes) four Hydrogen pyrazoles [1,2d] [1,4,5]-oxa- diazepine -7,9- diketone and compound pinoxaden shown in 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.
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