CN103664939A - Synthesis method of pyraclonil - Google Patents

Abstract

The invention relates to a weedicide preparation method which comprises the following steps: adding 0.35 mol of sodium hydride into 100 mL of tetrahydrofuran, and cooling to 0 DEG C; in a nitrogen atmosphere, dropwisely adding a suspension of 0.17 mol of 5-amino-1-(3-chloro-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-yl)-4 pyrazolecarbonitrile in 500 mL of tetrahydrofuran; stirring the mixture for 1.5 hours; at 15 DEG C, dropwisely adding a solution of 0.17 mol of propargyl chloride in 20 mL of tetrahydrofuran; stirring at room temperature for 3 hours, and cooling the mixture; dropwisely adding 0.17 mol of iodomethane, and reacting at 15 DEG C for 3 hours; dropwisely adding water, and extracting the mixture with ethyl acetate; separating the organic phase, drying, and concentrating; and recrystallizing the residue with ethyl acetate to obtain pyraclonil. Test results indicate that the process route provided by the invention is feasible, and the product yield can be up to 90%.

Description

The synthetic method of pyraclonil

Technical field

The present invention relates to a kind of preparation method of weedicide.

Background technology

Pyraclonil (Pyraclonil) is herbicide for paddy field, is found at first by Ai Gefu company.After by chemical company Kyoyu agricultural development for Japanese Agricultural.Pyraclonil is proporphyrinogen oxidase inhibitor, it is a kind of contact killing type weedicide, by first protoporphyrinogen oxidase in vegetative nerve, gather and bring into play drug effect, can effectively suppress the weeds of all kinds of weeds, barnyard grass, broadleaf weeds and nutgrass flatsedge and resistance to sulfonylurea herbicide.Its English chemical name is: and 1-(3-chloro-4,5,6,7-tetrahydro-pyrazolo[1,5-a] pyridine-2-y1)-5 (methyl-prop-2-ynyl-amino)-1 H-pyrazole-4-carbonitrile.

This compound outward appearance is white or tawny crystalline powder, content 98.5%, molecular formula C15H15ClN6, density 1.34,93～94.6 ℃ of fusing points.

Because this compound has excellent weeding activity, particularly can remove the weeds of resistance to sulfonylurea herbicide, the research and development of therefore this compound being carried out to synthesis technique have greater significance.

Summary of the invention

The present invention aims to provide the synthetic method that a kind of products collection efficiency reaches 90% pyraclonil.

The synthetic method of pyraclonil, comprising:

At room temperature the 5-Chlorovaleryl Chloride of 0.62mol is added drop-wise in the 150mL dichloromethane solution of 0.589mol aluminum chloride; Stir after 1 hour, drip the 25mL dichloromethane solution of the vinylidene chloride of 0.558mol, when ice-cooled, drip 100mL water, by solid materials suction filtration on diatomite; Filtrate water washing, dry organic phase is also concentrated; Resistates distills on rotatory evaporator, obtains the chloro-1-teracrylic acid of 1,1,7-tri--one;

Under-2 ℃ of conditions, 5.4mol hydrazine hydrate is added drop-wise to 1,1 of 0.54mol, in the 2000mL 2-propanol solution of the chloro-1-teracrylic acid of 7-tri--one; After stirring at room 12 hours, add 1.08mol potassium hydroxide, and by mixture reflux 5 hours; Reaction mixture is evaporated to dry, 100mL water and 100mL brine treatment for residue, be extracted with ethyl acetate, and organic phase salt water washing by dried over sodium sulfate and concentrate, obtains 2-diazanyl-4, and 5,6,7-tetrahydro-pyrazole is [1,5-a] pyridine also;

At room temperature by 2-diazanyl-4 of 13.1mmol, 5,6,7-tetrahydro-pyrazole is [1,5-a] 1 also] pyridine protection amino, then the mixture in 25mL ethanol stirs 30 minutes with 14.4mmol Ethoxy methylene malononitrile 99, again boiling point heating 3 hours, concentrated reaction mixture, purifies resistates with silica gel column chromatography, obtain 5-amino-1-(4,5,6,7-tetrahydro-pyrazole is [1,5-A] pyridine-2-yl also)-1H-pyrazoles-4-formonitrile HCN;

By 5-amino-1-(4 of 2.25mol, 5,6,7-tetrahydro-pyrazole is [1,5-A] pyridine 2-2-yl also)-1H-pyrazoles-4-formonitrile HCN is dissolved in the methylene dichloride of 30mL, in room temperature, by the SULPHURYL CHLORIDE of 2.25mol, process, mixture stirring was concentrated and obtain 5-amino-1-after 1 hour, and (3-chloro-4,5,6,7-tetrahydro-pyrazole is [1,5-A] pyridine-2-yl also)-1 H-pyrazoles-4-formonitrile HCN;

0.35mol sodium hydride is added in l00mL tetrahydrofuran (THF) and is cooled to 0 ℃; Under nitrogen atmosphere, drip 5-amino-1-(3-chloro-4,5,6,7-tetrahydro-pyrazole is [1, the 5-a] pyridine-2-yl also) suspension of-4 pyrazoles nitriles in 500mL tetrahydrofuran (THF) of 0.17mol; Mixture is stirred 1.5 hours; Then in 15 ℃, drip the solution of 0.17mol propargyl chloride in 20mL tetrahydrofuran (THF); In stirring at room after 3 hours, cooling mixture; And then drip 0.17rnol methyl iodide, then at 15 ℃, react 3 hours; Then drip water, and mixture is extracted with ethyl acetate; Organic phase is separated, be dried and concentrate; Residue re-crystallizing in ethyl acetate, obtains pyraclonil.

Test-results shows, operational path of the present invention is comparatively feasible, and products collection efficiency can be up to 90%.

Embodiment

Embodiment mono-

At room temperature the 5-Chlorovaleryl Chloride of 0.62mol is added drop-wise in the 150mL dichloromethane solution of 0.589mol aluminum chloride.Stir after 1 hour, drip the 25mL dichloromethane solution of the vinylidene chloride of 0.558mol, when ice-cooled, drip 100mL water, by solid materials suction filtration on diatomite.Filtrate water washing, dry organic phase is also concentrated.Resistates distills on rotatory evaporator, obtains 112.76g product, productive rate 93.8%, boiling point: 125 ℃/40Pa.

Under-2 ℃ of (acetone/dry ice) conditions, 5.4mol hydrazine hydrate is added drop-wise to 1,1 of 0.54mol, in the 2000mL 2-propanol solution of the chloro-1-teracrylic acid of 7-tri--one.After stirring at room 12 hours, add 1.08mol potassium hydroxide, and by mixture reflux 5 hours.Reaction mixture is evaporated to dry, 100mL water and 100mL brine treatment for residue.Be extracted with ethyl acetate, organic phase salt water washing, by dried over sodium sulfate concentrated, obtains yellow oil 29.29g, productive rate 35.6%.

At room temperature by 2-diazanyl-4 of 13.1mmol; 5; 6; 7 one tetrahydro-pyrazoles also [1; 5-a] 1] pyridine adopts appropriate means by amido protecting; then the mixture in 25mL ethanol stirs 30 minutes with 14.4mmol Ethoxy methylene malononitrile 99; at boiling point, heat 3 hours again, concentrated reaction mixture, by silica gel column chromatography for resistates, (hexane/ethyl acetate 1:1 is purified; obtain 5-amino-1-(4; 5,6,7-tetrahydro-pyrazole also [1; 5-A] pyridine-2-yl)-1H-pyrazoles-4-formonitrile HCN, productive rate 91%.

5-amino-1-of 2.25mol (4,5,6,7-tetrahydro-pyrazole is [1,5-A] pyridine 2-2-yl also)-1H-pyrazoles-4-formonitrile HCN is dissolved in the methylene dichloride of 30mL, in room temperature, by the SULPHURYL CHLORIDE of 2.25mol, processes.Mixture stirring was concentrated and obtains product, density 1.66, productive rate 99.8% after 1 hour.

0.35mol sodium hydride (80%) is added in l00mL tetrahydrofuran (THF) and is cooled to 0 ℃.Under nitrogen atmosphere, drip 5-amino-1-(3-chloro-4,5,6,7-tetrahydro-pyrazole is [1, the 5-a] pyridine-2-yl also) suspension of-4 pyrazoles nitriles in 500mL tetrahydrofuran (THF) of 0.17mol.Mixture is stirred 1.5 hours.Then in 15 ℃, drip the solution of 0.17mol propargyl chloride in 20mL tetrahydrofuran (THF).In stirring at room after 3 hours, cooling mixture.And then drip 0.17rnol methyl iodide, then at 15 ℃, react 3 hours.Then drip water, and mixture is extracted with ethyl acetate.Organic phase is separated, be dried and concentrate.Residue re-crystallizing in ethyl acetate, obtains product, productive rate approximately 90%.

Claims (1)

1. the synthetic method of pyraclonil, is characterized in that comprising:

At room temperature the 5-Chlorovaleryl Chloride of 0.62mol is added drop-wise in the 150mL dichloromethane solution of 0.589mol aluminum chloride; Stir after 1 hour, drip the 25mL dichloromethane solution of the vinylidene chloride of 0.558mol, when ice-cooled, drip 100mL water, by solid materials suction filtration on diatomite; Filtrate water washing, dry organic phase is also concentrated; Resistates distills on rotatory evaporator, obtains the chloro-1-teracrylic acid of 1,1,7-tri--one;

Under-2 ℃ of conditions, 5.4mol hydrazine hydrate is added drop-wise to 1,1 of 0.54mol, in the 2000mL 2-propanol solution of the chloro-1-teracrylic acid of 7-tri--one; After stirring at room 12 hours, add 1.08mol potassium hydroxide, and by mixture reflux 5 hours; Reaction mixture is evaporated to dry, 100mL water and 100mL brine treatment for residue, be extracted with ethyl acetate, and organic phase salt water washing by dried over sodium sulfate and concentrate, obtains 2-diazanyl-4, and 5,6,7-tetrahydro-pyrazole is [1,5-a] pyridine also;

At room temperature by 2-diazanyl-4 of 13.1mmol, 5,6,7-tetrahydro-pyrazole is [1,5-a] 1 also] pyridine protection amino, then the mixture in 25mL ethanol stirs 30 minutes with 14.4mmol Ethoxy methylene malononitrile 99, again boiling point heating 3 hours, concentrated reaction mixture, purifies resistates with silica gel column chromatography, obtain 5-amino-1-(4,5,6,7-tetrahydro-pyrazole is [1,5-A] pyridine-2-yl also)-1H-pyrazoles-4-formonitrile HCN;

By 5-amino-1-(4 of 2.25mol, 5,6,7-tetrahydro-pyrazole is [1,5-A] pyridine 2-2-yl also)-1H-pyrazoles-4-formonitrile HCN is dissolved in the methylene dichloride of 30mL, in room temperature, by the SULPHURYL CHLORIDE of 2.25mol, process, mixture stirring was concentrated and obtain 5-amino-1-after 1 hour, and (3-chloro-4,5,6,7-tetrahydro-pyrazole is [1,5-A] pyridine-2-yl also)-1 H-pyrazoles-4-formonitrile HCN;

0.35mol sodium hydride is added in l00mL tetrahydrofuran (THF) and is cooled to 0 ℃; Under nitrogen atmosphere, drip 5-amino-1-(3-chloro-4,5,6,7-tetrahydro-pyrazole is [1, the 5-a] pyridine-2-yl also) suspension of-4 pyrazoles nitriles in 500mL tetrahydrofuran (THF) of 0.17mol; Mixture is stirred 1.5 hours; Then in 15 ℃, drip the solution of 0.17mol propargyl chloride in 20mL tetrahydrofuran (THF); In stirring at room after 3 hours, cooling mixture; And then drip 0.17rnol methyl iodide, then at 15 ℃, react 3 hours; Then drip water, and mixture is extracted with ethyl acetate; Organic phase is separated, be dried and concentrate; Residue re-crystallizing in ethyl acetate, obtains pyraclonil.