CN109476603A - The method for preparing Boscalid - Google Patents
The method for preparing Boscalid Download PDFInfo
- Publication number
- CN109476603A CN109476603A CN201780044954.4A CN201780044954A CN109476603A CN 109476603 A CN109476603 A CN 109476603A CN 201780044954 A CN201780044954 A CN 201780044954A CN 109476603 A CN109476603 A CN 109476603A
- Authority
- CN
- China
- Prior art keywords
- boscalid
- solution
- raised temperature
- anhydrous
- alcohol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Wood Science & Technology (AREA)
- Dentistry (AREA)
- Plant Pathology (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Provide the method for preparing the crystal modification II of anhydrous Boscalid, this method includes the Boscalid solution provided in organic solvent system, the solution is heated to raised temperature, and the precipitation solid Boscalid from the solution, the raised temperature are enough to preferentially form the crystal modification II of anhydrous Boscalid.
Description
Cross reference to related applications
This application claims " prepared the side of Boscalid to the entitled of Department of Intellectual Property, Britain submission on August 4th, 2016
The priority of No. 1613462.9 GB patent application of method ", entire contents are incorporated herein by reference.
Technical field
The present invention relates to the methods for preparing Boscalid, more particularly to the method for the specific crystal formation for preparing Boscalid.
Background technique
Adopted name is the chloro- N- of compound 2- (4 ' chlorine [1,1 ' xenyl] -2- base)-Niacinamide of Boscalid
With structural formula I:
Boscalid is carboxyl acylamide fungicide, and serve as succinate dehydrogenase inhibitors (SDHI), i.e. mitochondria
Respiration inhibitor.The activity of the imide compound of this classification and these compounds for the first time in US 4,001,416 and US 5,
It is described in 330,995.
Boscalid is active as fungicide, and its at present with it is a series of for handle fungal infection and its
The preparation of generated disease is commercially available.
US 7,087,239 is related to the crystalline hydrate of niacin aniline and/or Benzanilide derivatives.US7,087,239
The synthesis and recycling of the hydrate of Boscalid of middle particular instantiation.The hydration is obtained by preparing anhydrous Boscalid first
Object, the anhydrous Boscalid obtain at the end of synthesis process as the solution in hot dimethylbenzene.After cooling, tied from the solution
Crystalline substance goes out Boscalid and is dried in vacuo in an oven.The anhydride is noted with following physical characteristic:
US 7,087,239 is disclosed can be by being dissolved into tetrahydrofuran for the anhydride in a solvent at 40 DEG C
(THF) in and acquired solution is added in water and forms the hydrate.Precipitating is isolated in the mixture obtained by as filtering
And it is dry, to obtain the monohydrate of Boscalid.The crystal modification of anhydrous Boscalid disclosed in US 7,087,239 exists
The herein referred to as crystal modification I of Boscalid.
US 7,241,896 is related to for producing 2- halogen-pyridine-2-carboxamide method.Disclose and instantiate Boscalid
Preparation.In these examples, Boscalid is by 2- chloro- 3- cigarette acyl chloride II and 2- (4- chlorphenyl) aniline molten
It is reacted to synthesize in agent system (specifically dimethylbenzene).It is organic by cooling down steadily after being extracted with sodium carbonate liquor
Solution crystallizes Boscalid.
We have found that the crystal modification for grinding anhydrous Boscalid disclosed in US 7,087,239 in water is tired
Difficult.Therefore, directly the crystal modification of Boscalid is configured to need to grind and/or the expectation preparation of fine grinding process is not one
The simple task of item.These preparations are, such as granula, microcapsulated granule, tablet, water dispersible granules, aqueous dispersion tablets, moisture loose powder
Agent or wettable powder for seed treatment, powder preparation and reactive compound existing preparation in a dispersed form, such as
The suspending agent of suspending agent, oil-based suspension, suspoemulsion or seed treatment.Before being configured to suspending agent, need Boscalid
Crystal modification aquation.
US 7,501,384 discloses the new crystal modification claimed as anhydrous Boscalid.Disclosed in US 7,501,384
Crystal modification is herein referred to as the crystal modification II of Boscalid.It is proposed in US 7,501,384, the knot of Boscalid
Brilliant variant II is particularly suited for manufacturing various preparations, and otherwise these preparations need prolonged grinding/fine grinding process.
The crystal modification II that US 7,501,384 describes Boscalid can be prepared by a method comprising the following steps:
A) anhydride of the crystal modification I of Boscalid is dissolved in polar organic solvent or aromatic hydrocarbon；And
B) anhydride of the crystal modification II of Boscalid is precipitated by the cooling solvent.
The alternative that the crystal modification II of Boscalid is prepared disclosed in US 7,501,384 includes:
A) the crystal modification I of Boscalid is heated to 150 DEG C or more until fusing；And
B) the thawing object is cooled down by the crystal seed of the crystal modification II of addition Boscalid.
US 7,501,384 describes the crystal modification II of Boscalid, has the property that
The key obtained from the Crystallographic Study of the crystal modification II of Boscalid using the single crystal diffractometer of Siemens
Parameter and structure cell matrix provide as follows in US 7,501,384:
Parameter illustrated above has following meanings:
The rib of a, b, c=structure cell is long；
α, beta, gamma=corresponding angle；And
Molecular number in Z=structure cell.
If the improvement preparation method of the crystal modification II of anhydrous Boscalid can be provided, it is particularly suitable in business
It is applied in scale, the method for variant II product with reproducible high yield, will have significant advantage.Preferably, the party
Method is easy to operate and easily controllable.
It was unexpectedly determined that it has now been discovered that the crystal modification II for forming the anhydrous Boscalid of high yield is to increase
At a temperature of occur.In contrast, lower temperature leads to the crystalline modifications I for preferentially forming anhydrous Boscalid.Specifically,
When precipitating Boscalid from dicyandiamide solution, surprisingly it has been found that Boscalid is from dicyandiamide solution at low temperature
Precipitating mainly or only produce the crystal modification I of anhydrous Boscalid, and improve the temperature and precipitation solid of dicyandiamide solution
Boscalid preferentially generates the crystal II variant of anhydrous Boscalid.
Summary of the invention
Therefore, in the first aspect, the present invention provides the method for the crystal modification II for preparing anhydrous Boscalid, the party
Method includes the Boscalid solution provided in organic solvent system, which is heated to raised temperature, and from the solution
Middle precipitation solid Boscalid, the raised temperature are enough to preferentially form the crystal modification II of anhydrous Boscalid.
In the present invention, the crystal modification II of anhydrous Boscalid is formed using raised temperature.As described above, with compared with
Low temperature is compared, and this raised temperature leads to the crystal modification II for preferentially forming anhydrous Boscalid.
Method of the invention uses Boscalid starting material.The Boscalid starting material is Boscalid organic molten
Solution in agent system.Any organic solvent system suitable for Boscalid can be used to be formed described in the embodiment
Boscalid starting material.The dicyandiamide solution can be single organic solvent or the mixture of two or more solvents.Properly
Solvent include polar organic solvent and aromatic hydrocarbon.Preferred polar organic solvent is alcohol, the polyalcohol including such as dihydric alcohol,
Ketone, ether, ester, amide and its mixture.
The example of suitable alcohol is C1To C8Alcohol, preferably C1To C5Alcohol.The alcohol can be linear chain or branched chain fatty alcohol, more excellent
Selection of land is ethyl alcohol, propyl alcohol and butanol.The alcohol can be alicyclic alcohol, such as cyclohexanol.The solvent may include polyalcohol, such as
Dihydric alcohol.The example of suitable dihydric alcohol is monoethylene glycol and polyethylene glycol, preferably ethylene glycol and diethylene glycol (DEG).
The example of suitable ketone is C3To C8Ketone, preferably C3To C6Ketone, more preferable acetone, butanone, pentanone and hexanone.These
Ketone can be straight chain, branch or cricoid, such as alkyl acetone and cyclohexanone.
The example of suitable ether is C3To C8Ether, preferably C3To C6Ether.These ethers can be straight chain, branch or cricoid, example
Such as dioxanes and tetrahydrofuran.
The example of suitable ester is C3To C8Ester, preferably C3To C6Ester, more preferable ethyl acetate and methyl acetate.
The example of suitable amide is C3To C8Amide, preferably C3To C6Amide, more preferable dimethylformamide.
Suitable aromatic solvent is benzene, toluene and dimethylbenzene.Dimethylbenzene is a kind of preferred solvent.
Suitable solvent is known in the art, and is commercially available.
It can be using the mixture of solvent as the dicyandiamide solution.For example, the organic solvent may include aromatic solvent
(such as benzene, dimethylbenzene or toluene) or cyclic alkane (such as cyclohexene) and one or more of aliphatic or alicyclic alcohol (such as hexamethylene
Alcohol), the group of one or more of ketone, one or more of ethers (such as cyclic ethers, such as tetrahydrofuran) or one or more of amides
It closes.
Organic solvent employed in method of the invention is preferably substantially free from water, to ensure anhydrous Boscalid most
Big yield.The organic solvent may include by weight at most 0.4% water, which can be by the solvent absorption in atmosphere.Most
Preferably, the organic solvent is not aqueous.
Boscalid solution can be formed in any suitable manner.For example, can be by the way that the solid of Boscalid will be removed
Other forms Boscalid except crystal modification II is dissolved in organic solvent system to form the solution.Or can have
Boscalid is synthesized in the presence of solvent.It is this field that the appropriate method of Boscalid is synthesized in solution in organic solvent
It is known.US 7,087,239 discloses the suitable synthetic route for being used to prepare Boscalid.
The method of the present invention includes the precipitation solid Boscalids from Boscalid solution in organic solvent.This is molten
Liquid is heated to raised temperature.The raised temperature is higher than environment temperature or room temperature, and is to precipitate preferentially to generate anhydrous pyridine acyl
The temperature of the crystal modification II of bacterium amine.Any suitable raised temperature can be used.Preferably, which is lower than pyridine
The boiling point of acyl bacterium amine aqueous solution.
Suitably raised temperature can be determined by the Boscalid material of analysis precipitating, especially temperature pair
It is whether sufficiently high for precipitating the variant II of anhydrous Boscalid.
The raised temperature is preferably at least 35 DEG C, more preferably at least 40 DEG C, and still more preferably at least 45 DEG C.It is testing
In, it has been found that, after being heated to 45 DEG C of temperature, Boscalid is precipitated from the solution in organic solvent and is generated comprising by weight
The solid Boscalid material of the crystal modification II of the amount of meter 30%.
It is highly preferred that be heated at least 50 DEG C, still more preferably at least 55 DEG C, still more preferably at least 60 DEG C of temperature it
Afterwards, Boscalid is precipitated out from solution.In experimentation it has been found that after being heated to 65 DEG C of temperature, from organic solvent
In solution in precipitation solid Boscalid result in by weight 100% anhydrous Boscalid crystal modification II.
As described above, the raised temperature is preferably lower than the boiling of the solution of organic solvent and Boscalid starting material
Point.Fusing point of the raised temperature also below the crystal modification II of anhydrous Boscalid.
The upper limit of the raised temperature will depend on used specific solvent or dicyandiamide solution.The raised temperature is preferred
Lower than 140 DEG C, more preferably less than 130 DEG C, still more preferably less than 120 DEG C, still more preferably below 110 DEG C.In preferred embodiment party
In case, solid Boscalid starting material is heated to lower than 100 DEG C, more preferably less than 90 DEG C, still more preferably less than 85 DEG C, still
More preferably less than 80 DEG C of raised temperature.
It is preferable to use the raised temperature within the scope of 30 DEG C to 130 DEG C, more preferably from 35 DEG C to 120 DEG C, even more preferably from
For from 40 DEG C to 110 DEG C, it is still preferred to for from 45 DEG C to 100 DEG C, wherein preferred range is 50 DEG C to 90 DEG C, more preferably 55
DEG C to 85 DEG C, still more preferably 60 DEG C to 80 DEG C.60 DEG C to 70 DEG C of temperature is particularly preferred, wherein about 65 DEG C of temperature is led
Cause the variant II of the anhydrous Boscalid of formation substantially by weight 100%.
Any suitable technology can be used to realize and precipitate Boscalid material from organic solvent.It is precipitated from solution
Boscalid can carry out at elevated temperatures.For example, can be (such as logical by removing organic solvent at elevated temperatures
Pervaporation is such as evaporated under reduced pressure) it is precipitated to realize.
Or after solution is heated to raised temperature, can lower than the raised temperature at a temperature of from solution
In be settled out Boscalid.It specifically, can be by the way that the Boscalid saturated solution in solvent be cooled to from raised temperature
The lower temperature that solid Boscalid precipitating occurs goes out Boscalid material to realize from organic solvent deposit.
As other alternative solution, this method can use the combination of above-mentioned technology, it can at elevated temperatures
Start the precipitating of solid Boscalid material, and then cools down solution, such as precipitate other solid.
Cooling can by it is continuous, gradually or combinations thereof in a manner of carry out.
The precipitating of Boscalid product can carry out in the presence of Boscalid crystal seed in organic solvent, preferably anhydrous
It is carried out in the presence of the crystal seed of the crystal modification II of Boscalid.
Method of the invention can be conducted batch-wise or in a continuous manner.
Any suitable device can be used to carry out the precipitating of Boscalid crystal modification II.Suitable device is in ability
It is known in domain, and is commercially available.
In another aspect, the present invention provides the crystal modifications of the anhydrous Boscalid comprising being prepared by the above method
The Fungicidal formulations of II.
Brief description
FTlR spectroscopic methodology record IR spectrum can be used.
Fig. 1 is the IR spectrum of the crystal modification II of anhydrous Boscalid；
Fig. 2 is the IR spectrum of the crystal modification I of anhydrous Boscalid.
Specific embodiment
Embodiment of the present invention will be described only for the purpose of illustration by following specific examples.
In the examples below, unless otherwise indicated, percentage is weight percent.
Embodiment
Embodiment 1
Boscalid is prepared according to following general reaction scheme:
Boscalid solution of the following preparation in dimethylbenzene:
396g (1.944mol) 2- -4 '-chlordiphenyl of amino in 311g dimethylbenzene is encased in reaction vessel, and stirred
The mixture is until obtaining uniform solution.By the chloro- 3- nicotinoyl solutions of chlorine of 349g (1.984mol) 2- in 233g dimethylbenzene
It is added in the reaction vessel, and gained mixture is allowed to be heated to 30 DEG C.
Gained mixture was heated to 95 DEG C of raised temperature within 4 to 5 hours time.Simultaneously using external washer
It carries out absorbing the hydrogen chloride (HCl) for removing and being generated by reaction by spray tower using water and aqueous slkali.The reaction mixture is existed
It is further kept for 30 minutes at identical raised temperature with stirring, to remove the HCL of all traces.Hereafter, by the reaction
Mixture adjoint be slowly stirred within 5 to 7 hours time is cooled to 30 DEG C.
Finally the solution is cooled to room temperature, causes to be settled out solid Boscalid material, solution is removed by filtration.It is logical
It crosses and is dried in vacuo the removing trace dimethylbenzene from the sediment in an oven.
Using Brooker company (Bruker) model Tensor37 spectrometer, (recording wavelength is 550 to 4000cm-1, with most
High-resolution 4cm-1Scanning 16 times), the Boscalid material recycled using infrared (IR) analysis of spectral method.Analysis shows the solid
Product is the crystal modification II of anhydrous Boscalid.
Embodiment 2
750g toluene is encased in reaction vessel in a nitrogen atmosphere.At room temperature with stirring addition 335g 2- chlorine
Niacin.35g dimethylformamide (DMF) is added into the mixture, and gained reaction mixture is slowly heated under stiring
To 40 DEG C.300g thionyl chloride was added within 1 hour time.By washing the hydrogen chloride (HCl) and two except dereaction release
Sulfur oxide (SO2).Hereafter, which is kept under nitrogen atmosphere, and is kept for 4 to 5 hours at 60 DEG C, until acid is complete
(being monitored with HPLC) occurs for full response.Later, excessive thionyl chloride is removed at 60 DEG C to 75 DEG C and under decompression.By institute
Mixture is obtained to be cooled to room temperature.
500g toluene and 200g triethylamine (TEA) is used to dilute under stiring in cooling mixture.At 45 DEG C, 30 to
400g 4 '-chlordiphenyl -2- amine is added in 45 minutes time into this homogeneous mixture, and it is small to be stirred for mixture 4 to 5
When make reaction complete.By addition water and it is stirred for that the mixture is quenched within 2 to 3 hours.
Organic layer is separated to and is maintained at 60 DEG C of raised temperature.The mixture is filtered to remove insoluble impurities.?
It is slowly stirred and lower the mixture is finally cooled to 10 DEG C to 15 DEG C.By filtering and drying separation solid, 450g is obtained extremely
480g Boscalid.
As, by the IR spectrum analysis solid, shown that the solid product is that the crystallization of anhydrous Boscalid becomes in embodiment 1
Body II.
Embodiment 3
792g (3.888mol) 2- -4 '-chlordiphenyl of amino in 622g dimethylbenzene is encased in reaction vessel, and stirred
The mixture is until obtaining uniform solution.By the chloro- 3- nicotinoyl solutions of chlorine of 698g (3.968mol) 2- in 466g dimethylbenzene
The temperature for being added in the reaction vessel, and gained mixture being allowed to be heated to 30 DEG C.
Gained mixture was heated to 95 DEG C of raised temperature within 4 to 5 hours time.Simultaneously using external washer
It carries out absorbing the hydrogen chloride (HCl) for removing and being generated by reaction by spray tower using water and aqueous slkali.The reaction mixture is existed
With the time of the further holding 2 to 3 hours of stirring at identical raised temperature, to remove all trace HCl.
The crystal seed of the crystal modification II of the anhydrous Boscalid of gained mixture is inoculated with, the precipitating of solid material is caused,
The solid material is collected by filtration.Trace dimethylbenzene is removed by being dried in vacuo from the sediment in an oven.
Using 37 spectrometer of Brooker company (Bruker) model Tensor, (recording wavelength is 550 to 4000cm-1, with most
High-resolution 4cm-1Scanning 16 times), the solid material collected using infrared (IR) analysis of spectral method.Analysis shows the solid product
It is the crystal modification II of anhydrous Boscalid.
Embodiment 4
Prepare the carbonyl intermediates of 375g chlorine apellagrin according to step described in embodiment 2, and with 400g4 '-chlordiphenyl-
The reaction of 2- amine, obtains crude Boscalid product.The product is washed repeatedly with tetrahydrofuran (THF), and with 850g isopropyl
Alcohol dilution.Acquired solution is heated to 60 DEG C and is kept for 2 to 3 hours at such a temperature.
Cooling gained mixture is to obtain solid sediment.The solid is separated by filtering and drying.
As, by the IR spectrum analysis solid, shown that the solid product is that the crystallization of anhydrous Boscalid becomes in embodiment 1
Body II.
For the step of studying influence of the temperature to solid Boscalid material obtained in this method, repeating embodiment 1,
Wherein solid Boscalid is settled out from a series of xylene solution for being maintained at different raised temperature before cooling.
As a result it summarizes in the following table.
From upper table summarize result can be seen that the anhydrous Boscalid precipitated from organic solvent form depend on from
The temperature of the Boscalid solution wherein precipitated.Specifically, it is generated from the precipitating of the dimethylbenzene for the temperature for being heated to 65 DEG C
The crystal modification II of 100% anhydrous Boscalid.In contrast, only from the precipitating for the xylene solution for being heated to just 30 DEG C
The crystal modification II of 10% to 20% anhydrous Boscalid is produced, has primarily formed the crystallization of Boscalid at such a temperature
Variant I.
Claims (27)
1. a kind of method for the crystal modification II for preparing anhydrous Boscalid, the method includes providing in organic solvent system
Boscalid solution, the solution is heated to raised temperature, and the precipitation solid Boscalid from the solution, it is described
Raised temperature is enough to preferentially form the crystal modification II of anhydrous Boscalid.
2. according to the method described in claim 1, wherein the dicyandiamide solution includes polar organic solvent, aromatic hydrocarbon or its mixing
Object.
3. according to the method described in claim 2, wherein the polar organic solvent is selected from alcohol, ketone, ether, ester, amide and its mixes
Close object.
4. according to the method described in claim 3, wherein the alcohol is linear chain or branched chain aliphatic alcohol or alicyclic alcohol.
5. according to the method described in claim 4, wherein the alcohol is selected from ethyl alcohol, propyl alcohol, butanol, cyclohexanol, ethylene glycol and two
Glycol.
6. according to the method described in claim 3, wherein the ketone is selected from acetone, butanone, pentanone and hexanone.
7. according to the method described in claim 3, wherein the ether is selected from dioxanes and tetrahydrofuran.
8. according to the method described in claim 3, wherein the ester is selected from ethyl acetate and methyl acetate.
9. according to the method described in claim 3, wherein the amide is dimethylformamide.
10. according to the method described in claim 2, wherein the aromatic solvent is selected from benzene, toluene and dimethylbenzene.
11. method according to any preceding claims, wherein the dicyandiamide solution is substantially free of water.
12. method according to any preceding claims, wherein by will except Boscalid solid crystal variant II it
Outer Boscalid form, which is dissolved in the organic solvent system, forms the solution.
13. method according to any one of claim 1 to 11, wherein by the presence of the organic solvent system
Boscalid is synthesized to form the solution.
14. method according to any preceding claims, wherein the raised temperature is lower than the boiling point of the solution.
15. method according to any preceding claims, wherein the raised temperature is at least 45 DEG C.
16. according to the method for claim 15, wherein the raised temperature is at least 55 DEG C.
17. according to the method for claim 16, wherein the raised temperature is at least 65 DEG C.
18. method according to any preceding claims, wherein the raised temperature is lower than 100 DEG C.
19. according to the method for claim 18, wherein the raised temperature is lower than 85 DEG C.
20. according to the method for claim 19, wherein the raised temperature is from 55 DEG C to 85 DEG C.
21. method according to any preceding claims, wherein solid Boscalid is deposited in the raised temperature
Lower generation.
22. method according to any preceding claims, wherein solid Boscalid be deposited in it is raised lower than described
Occur at a temperature of temperature.
23. method according to any preceding claims, wherein helping to precipitate by adding crystal seed into the solution.
24. according to the method for claim 23, wherein the crystal seed is the crystal of the crystal modification II of anhydrous Boscalid.
25. method according to any preceding claims, wherein the method is conducted batch-wise or in a continuous manner.
26. the method that one kind prepares the crystal modification II of anhydrous Boscalid substantially as described above.
27. a kind of Fungicidal formulations, the Fungicidal formulations include method according to any preceding claims preparation
The crystal modification II of anhydrous Boscalid.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1613462.9A GB2552699B (en) | 2016-08-04 | 2016-08-04 | Process for preparing boscalid |
| GB1613462.9 | 2016-08-04 | ||
| PCT/CN2017/094624 WO2018024145A1 (en) | 2016-08-04 | 2017-07-27 | Process for preparing boscalid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109476603A true CN109476603A (en) | 2019-03-15 |
Family
ID=60940414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780044954.4A Pending CN109476603A (en) | 2016-08-04 | 2017-07-27 | The method for preparing Boscalid |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN109476603A (en) |
| GB (1) | GB2552699B (en) |
| TW (1) | TWI733869B (en) |
| WO (1) | WO2018024145A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023062649A1 (en) * | 2021-10-14 | 2023-04-20 | Natco Pharma Limited | An improved process for the preparation of anhydrous crystalline form-i of boscalid |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1575281A (en) * | 2001-11-02 | 2005-02-02 | 巴斯福股份公司 | Method for producing 2-halogen-pyridine-carboxylic acid amides |
| CN1751026A (en) * | 2003-02-14 | 2006-03-22 | 巴斯夫股份有限公司 | Novel crystalline modification of the anhydrate of boscalid |
| CN103073489A (en) * | 2013-02-06 | 2013-05-01 | 利民化工股份有限公司 | Preparation method of Boscalid |
| CN103980192A (en) * | 2014-01-20 | 2014-08-13 | 泰州百力化学股份有限公司 | Selective synthesis method of cyprosulfamide with different crystal forms |
| CN105541709A (en) * | 2016-02-25 | 2016-05-04 | 尚振华 | Method for preparing boscalid |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT1432685E (en) * | 2001-09-25 | 2005-07-29 | Basf Ag | CRYSTALLINE HYDRATES OF NICOTHINIC ACID AND BENZOYLENYLIDAN ANILIDA DERIVATIVES |
-
2016
- 2016-08-04 GB GB1613462.9A patent/GB2552699B/en not_active Expired - Fee Related
-
2017
- 2017-07-27 WO PCT/CN2017/094624 patent/WO2018024145A1/en active Application Filing
- 2017-07-27 CN CN201780044954.4A patent/CN109476603A/en active Pending
- 2017-08-02 TW TW106126004A patent/TWI733869B/en not_active IP Right Cessation
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1575281A (en) * | 2001-11-02 | 2005-02-02 | 巴斯福股份公司 | Method for producing 2-halogen-pyridine-carboxylic acid amides |
| CN1751026A (en) * | 2003-02-14 | 2006-03-22 | 巴斯夫股份有限公司 | Novel crystalline modification of the anhydrate of boscalid |
| CN103073489A (en) * | 2013-02-06 | 2013-05-01 | 利民化工股份有限公司 | Preparation method of Boscalid |
| CN103980192A (en) * | 2014-01-20 | 2014-08-13 | 泰州百力化学股份有限公司 | Selective synthesis method of cyprosulfamide with different crystal forms |
| CN105541709A (en) * | 2016-02-25 | 2016-05-04 | 尚振华 | Method for preparing boscalid |
Non-Patent Citations (1)
| Title |
|---|
| 禹凯等: "pH值对啶酰菌胺晶型的影响", 《精细化工中间体》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201808904A (en) | 2018-03-16 |
| TWI733869B (en) | 2021-07-21 |
| GB2552699A (en) | 2018-02-07 |
| GB2552699B (en) | 2021-03-10 |
| WO2018024145A1 (en) | 2018-02-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7999106B2 (en) | Processes for the preparation of clopidogrel hydrogen sulfate polymorphic form I | |
| US9090647B2 (en) | Crystalline forms of rebaudioside B | |
| ES2542610T3 (en) | Preparation process of 4- {4 - [({[4-chloro-3- (trifluoromethyl) -phenyl] amino} carbonyl) amino] -3-fluorophenoxy} -N-methylpyridine-2-carboxamide, its salts and monohydrate | |
| JP5305248B2 (en) | New nateglinide crystals | |
| CN102977011A (en) | Process for preparing pyridinamines and novel polymorphs thereof | |
| UA121458C2 (en) | Process for preparing clomazone, novel form and use of the same | |
| US10364225B2 (en) | Process for preparing boscalid | |
| CN107922352A (en) | The method for preparing protein deacetylase inhibitors | |
| CN109476603A (en) | The method for preparing Boscalid | |
| TWI756173B (en) | Process for preparing boscalid | |
| JP5280115B2 (en) | Method for producing p-phenylenebis (trimellitic acid monoester anhydride) | |
| CN106243029B (en) | Method for preparing boscalid | |
| CN107698563B (en) | Method for preparing neratinib maleate crystal form | |
| CN101534644B (en) | Process for preparing pyridinamines and novel polymorphs thereof | |
| CN109476604A (en) | The method for being used to prepare Boscalid | |
| AU673732B2 (en) | Piperazinylpyridinyl water clathrates | |
| CN109563044A (en) | The method for being used to prepare Boscalid | |
| JPH07196620A (en) | Production of 8-oxyquinoline-aluminum salt | |
| CN116041372A (en) | Sulfur-nitrogen heterocyclic alkane intermediate compound, preparation method and application thereof | |
| CN109988103A (en) | A method of synthesis fluazinam | |
| GB2564284A (en) | Thiamethoxam and uses thereof | |
| CN117003689A (en) | Crystal form of iodophosphate and preparation method thereof | |
| EP3464283A1 (en) | Method for producing heterocyclic compounds | |
| CN106187907A (en) | A kind of synthetic method of bendazol | |
| PL186740B1 (en) | Methods of manufacturing polymorphous form i and form ii of 17 beta-(n-t-butylcarbamyl)-4-azo-5-androst-1-en-3-one in basically pure form |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |