CN110240566A - The synthetic method of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles - Google Patents
The synthetic method of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles Download PDFInfo
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- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
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Abstract
The invention discloses 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles synthetic method, it include: at 0-5 DEG C, to 2, the sodium nitrite solution that the ethanol solution and mass concentration that 2,6- dichlor-4-trifluoromethyl aniline salt is added dropwise in the ethanol solution hydrochloride of 3- dicyano ethyl propanoate simultaneously are 40-45%；Reaction solution keeps the temperature 2-12h at 0-5 DEG C, until reproducibility reagent is added dropwise into reaction solution to remove excessive nitrous acid in reaction solution, until nitrous acid is removed completely in reaction solution after 2,6- dichlor-4-trifluoromethyl aniline≤0.5% in reaction solution；At 10-15 DEG C, ammonium hydroxide and ethyl alcohol are added in reaction solution, so that pH >=11 of reaction solution, keep the temperature 8-24h.The synthetic method has broken the technology prejudice of those skilled in the art, has saved cost, and substantially reduced the generation of " three wastes ".
Description
Technical field
The present invention relates to the preparation technical fields of fine chemical product, more particularly to a kind of 5- Amino 3 cyano-
The synthetic method of 1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles.
Background technique
5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles abbreviation pyrazole ring, is synthetic pesticide
The important intermediate of Fipronil and ethiprole.Sterling is white crystalline solid, and industrial goods are fawn solid, fusing point 141~
142 DEG C, dissolve in methanol, ethyl alcohol, acetone, dichloroethanes and ethyl acetate.The height of its final product quality quality and combined coefficient,
Main influence will be generated on the insecticidal effect of Fipronil and ethiprole.
Fipronil is that a kind of Phenylpyrazole insecticides, insecticidal spectrum are wide, to pest based on stomach poison function, have concurrently tag and
Certain systemic action, mechanism of action be hinder insect γ-aminobutyric acid control chloride metabolism, therefore to aphid,
The important pests such as leafhopper, plant hopper, lepidopterous larvae, flies and coleoptera have very high insecticidal activity, to crop without phytotoxicity.The medicine
Agent imposes on soil, can also foliar spray, corn root leaf A, wireworm and cutworm can be effectively prevented by imposing on soil；Foliage spray
When, there is high-level preventive effect to diamondback moth, cabbage butterfly, rice thrips etc., and the lasting period is long.By many years developing research and development, Fipronil
It is still at present an efficient pesticides very popular.
Ethiprole is to be belonged to the second generation by the Insecticidal and acaricidal agent of rhone-poulenc discovery, Beyer Co., Ltd's exploitation and acted on
It is effective to a variety of chewing types and sucking pest under the low dosage of the insecticide of GABA, it can be used for seed treatment and foliar spray, it is main
It is used to prevent and treat the insect pests such as thrips, stinkbug, curculionid, beet gelechiid, aphid, plant hopper and locust, activity is also shown to certain aleyrodids.
At present for the study on the synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles, essence
On be all to be carried out by diazo-reaction, synthetic route is as shown in Figure 1.Traditional diazo-reaction, sour theory
Dosage be 2mol (the .4 editions Beijing Zeng Zhaoqiong, Li Jingning organic chemistry volume two [M]: Higher Education Publishing House, 2004:
106.), acid dissolves arylamine first, generates nitrous acid secondly with sodium nitrite, finally regenerates diazonium salt, since diazonium salt holds
It is more stable easily to decompose the ability only in excessive acid solution, so actually acid amount often reaches 3mol when diazotising.
Synthesis for 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles, is primarily present as follows
Patent document, Chinese granted patent: CN100593540C discloses a kind of 5- Amino 3 cyano -1- (2,6- bis- chloro- 4- trifluoros
Aminomethyl phenyl) pyrazoles preparation method, with 2,6- dichlor-4-trifluoromethyl aniline be raw material, using sulfuric acid as reaction medium, be added dropwise
The aqueous solution of sodium nitrite obtains the diazonium salt solution of 2,6- dichlor-4-trifluoromethyl aniline by diazo-reaction, adds
2,3- dicyano ethyl propanoates reaction, then again under weak basic condition in the symphysis of organic solvent middle ring at 5- Amino 3 cyano-
1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles.Although the patent avoids the use of the concentrated sulfuric acid and glacial acetic acid, yield also from
70% has been increased to 75.4%, but sulfuric acid dosage is 4~6mol, and reaction produces a large amount of spent acid, and " three wastes " processing is difficult, and
Yield is low.
Chinese granted patent: CN1137090C discloses a kind of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl
Phenyl) pyrazoles preparation method, Cymag, cyan-acetic ester, paraformaldehyde react in acidic alcohol obtains 2,3- dicyan
Base ethyl propionate crude product sequentially adds acidic alcohol, 2,6- dichlor-4-trifluoromethyl aniline, nitrous acid into the crude product solution
Sodium obtains 2,3- dicyano -2- [2,6- dichlor-4-trifluoromethyl phenyl) azo group] ethyl propionate crude product, at 0 DEG C to
Ammonia cyclization is passed through in the crude product solution, extracted, crystallize after obtain 5- Amino 3 cyano -1- (2,6- bis- chloro- 4- fluoroforms
Base phenyl) pyrazoles, yield 78%.Patent toxic articles Cymag synthesizes 2,3- dicyano ethyl propanoate, yield 77%, reaction
After remain Cymag in the solution and reacted with hydrochloric acid and generate the hydrogen cyanide gas that is in extreme danger, exist in production very big
Security risk.And 2,3- dicyano -2- [2,6- dichlor-4-trifluoromethyl phenyl) azo group] ethyl propionate, it needs at 0 DEG C
Under be passed through ammonia and carry out cyclization, plant operations are difficult and operating cost is high.
Chinese granted patent: CN103396366B discloses a kind of 5- Amino 3 cyano -1- (chloro- 4- fluoroform of 2,6- bis-
Base phenyl) pyrazoles production method, although which avoids the use of sulfuric acid, but react and still need a large amount of hydrochloric acid or acetic acid
Participation, the patent hydrochloric acid dosage be 8.3mol.The patent is substantially still that 2,6- dichlor-4-trifluoromethyl aniline generates diazonium
The salt mechanism with the reaction of 2,3- dicyano ethyl propanoate again, if sour dosage is insufficient when reaction, the diazonium salt of generation is easy and not anti-
The arylamine coupling answered, generates diazoamino compound.Meanwhile diazonium salt chemical property is very active, only in aqueous solution and compared with
Stablize under low temperature, increase temperature and then decompose, is heated, friction or shock are easy decomposition explosion.Therefore, 2,6- are largely prepared
, inherently there is security risk in the technique that dichlor-4-trifluoromethyl aniline diazonium salt is reacted with 2,3- dicyano ethyl propanoate again.
And the patent need to be added solid sodium nitrite, there are solid materials to add speed non-uniform problem when the practical operation of workshop, is easy
Locality sodium nitrite excessive response temperature lag is caused, so as to cause security risks such as fire explosions.
Summary of the invention
The purpose of the present invention is to provide the conjunctions of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles
At method, solve one or more of the above-mentioned prior art problem.
The synthetic method of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles, comprising:
S1, at 30-35 DEG C, by 2,6- dichlor-4-trifluoromethyl aniline, HCl and ethyl alcohol mix, obtain 2,6- bis-
The ethanol solution of chloro- 4- trifluoromethylbenzene amine salt, wherein the molar ratio of HCl and 2,6- dichlor-4-trifluoromethyl aniline is 0.5-
0.75；
Under room temperature, 2,3- dicyano ethyl propanoate, HCl and ethyl alcohol are mixed, 2,3- dicyano ethyl propanoate is obtained
Ethanol solution hydrochloride, wherein 2,3- dicyano ethyl propanoates and 2, the molar ratio of 6- dichlor-4-trifluoromethyl aniline are 1:1,
The molar ratio of HCl and 2,3- dicyano ethyl propanoate is 0.5-0.75；
S2, at 0-5 DEG C, into the ethanol solution hydrochloride of 2,3- dicyano ethyl propanoate simultaneously be added dropwise the chloro- 4- of 2,6- bis-
The ethanol solution and mass concentration of trifluoromethylbenzene amine salt are the sodium nitrite solution of 40-45%, wherein 2,6- bis- chloro- 4- tri-
The molar ratio of methyl fluoride aniline and sodium nitrite is 1:1-1:1.2, obtains reaction solution；
S3, the step S2 reaction solution keep the temperature 2-12h at 0-5 DEG C, until reaction solution in the chloro- 4- trifluoro of 2,6- bis-
After methylaniline≤0.5%, reproducibility reagent is added dropwise into reaction solution to remove excessive nitrous acid in reaction solution, until reaction
Nitrous acid is removed completely in liquid；
S4, at 10-15 DEG C, ammonium hydroxide and ethyl alcohol are added in the step S3 treated reaction solution, so that reaction solution
PH >=11, keep the temperature 8-24h；
S5, post-processing.
The synthetic route of the application is as shown in Fig. 2, theoretically, 2, the 6- dichlor-4-trifluoromethyl aniline of 1mol need to only disappear
Consume the HCl of 1mol；And existing diazotising synthetic route is as shown in Figure 1, theoretically, the 2 of 1mol, 6- dichlor-4-trifluoromethyl
Aniline needs to consume the HCl of 2mol；The sour dosage of the synthetic route of the application has broken the technology prejudice of those skilled in the art,
That is 2, the 6- dichlor-4-trifluoromethyl aniline of 1mol at least consumes the HCl of 2mol, has unexpected technical effect.
And in the actual production process, dosage sour in diazotising synthetic route is much larger than theoretical value, the reason is that the road
The diazonium salt generated in line is easy to decompose, just more stable only in excessive acid solution, so actually acid amount when diazotising
Often reach 3mol.Chinese granted patent CN 103396366B, in preparation 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyls
Phenyl) pyrazoles when, hydrochloric acid dosage is even more to have reached 8.3mol.
And in the synthetic route of the application, it is contemplated that sour cost is cheap relative to other raw materials, and therefore, sour dosage can be slightly
It is excessive, but total dosage of acid is also no more than 1.5mol.Being greatly lowered for sour dosage, it is cost-saved, and can largely reduce
The discharge of " three wastes ", while the also cost of reduction processing " three wastes ".
Wherein, in step S1, the ethanol solution and preparation 2,3- dicyano of 2,6- dichlor-4-trifluoromethyl aniline salt are prepared
The sequence of the ethanol solution hydrochloride of ethyl propionate is not construed as limiting.
In step S2, the ethanol solution hydrochloride of 2,3- dicyano ethyl propanoate is first added into reactor, then be added dropwise simultaneously
The ethanol solution and mass concentration of 2,6- dichlor-4-trifluoromethyl aniline salt are the sodium nitrite solution of 40-45%.
Since 2,6- dichlor-4-trifluoromethyl aniline is alkaline matter, extra hydrochloric acid will necessarily be consumed by reacting with acid, because
This, in step sl, 2,6- dichlor-4-trifluoromethyl anilines and a small amount of hydrochloric acid form 2,6- dichlor-4-trifluoromethyl aniline
With part 2,6- dichlor-4-trifluoromethyl aniline salt；Again in step s 2, afterwards plus 2,6- dichlor-4-trifluoromethyl aniline and portion
Divide 2,6- dichlor-4-trifluoromethyl aniline salt, the dosage of hydrochloric acid can be saved.
The nitrous that the ethanol solution and mass concentration that 2,6- dichlor-4-trifluoromethyl aniline salt is added dropwise simultaneously are 40-45%
Acid sodium solution refers to by controlling rate of addition, guarantees that above two solution starts simultaneously at dropwise addition, and drip simultaneously as far as possible
Finish.It is designed in this way, can avoid a large amount of preparation 2, the 6- dichlor-4-trifluoromethyl aniline diazonium salts of preparation.The diazonium salt chemistry of generation
Property is very active, only stablizes in aqueous solution under lower temperature, increases temperature and then decomposes, and is heated, rubs or hits
It is easy decomposition explosion.Therefore, the route of the application can solve the security risk of the Route Generation diazonium salt technique of the prior art.
Solid can be solved relative to solid sodium nitrite is used using the sodium nitrite solution that mass concentration is 40-45%
It is uneven that material adds speed, locality sodium nitrite excessive response temperature lag is be easy to cause, so as to cause fire explosion
The problem of.
In some embodiments, the hydrochloric acid solution that HCl is 30%-35% from mass concentration.Avoid the concentrated sulfuric acid
With the use of glacial acetic acid, the waste acid treatment that the concentrated sulfuric acid and glacial acetic acid generate is more difficult.
In some embodiments, in step S3, sampling detects 2,6- dichlor-4-trifluoromethyl with high performance liquid chromatography
Aniline≤0.5%.
In some embodiments, in step S3, the reproducibility reagent is in urea, ammonium sulfite or sodium hydrogensulfite
At least one.
Above-mentioned reproducibility reagent is to remove nitrous acid, such as the reaction equation of urea and nitrous acid is as follows: 2HNO2
+CO(NH2)2===N2+CO2+3H2O；Nitrous acid can be decomposed into nitrogen and carbon dioxide volatilization removal.
Chinese granted patent CN 103396366B removes nitrous acid by the way of extraction, specific as follows:
Sampling analysis 2, for 6- dichlor-4-trifluoromethyl aniline content less than 0.8%, the water measured is added in no diazonium salt,
After stirring half h, stratification, layer oily matter is spare, after upper aqueous layer is extracted with quantitative toluene, merges grease；It is above-mentioned
The method of extraction removes nitrous acid, it is necessary to reaction is divided into two reaction kettles and is carried out, the diazonium kettle as described in above-mentioned patent with
It is cyclized kettle, and the application removes nitrous acid by the way that at least one of urea, ammonium sulfite or sodium hydrogensulfite is added, and only needs
It wants a reaction kettle can be completed, has saved production cost.
In some embodiments, the mass concentration of reproducibility reagent is the solution of 35-40%.Use solution, operation letter
Just, and avoidable investment solid to react non-uniform problem.
In some embodiments, non-discolouring anti-to confirm with starch potassium iodide paper test by sampling in step S3
The nitrous acid in liquid is answered to be removed completely.
In some embodiments, in step S4, the mass concentration of the ammonium hydroxide is 20-30%.Use the ammonia of low concentration
Water, relative to using ammonia easy to operate, and " three wastes " that generate are easier to handle.
In some embodiments, in step S5, the post-processing includes:
The de- ethyl alcohol of decompression will be passed through by reaction solution after step S4 processing；
Toluene is added and water carries out extracting and demixing；
Toluene layer solvent is subjected to freezing and crystallizing, later by filtering and drying, obtains the 5- Amino 3 cyano -1-
(2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles.
By above-mentioned post-processing approach, obtained 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl)
The purity and high income of pyrazoles.Its purity is up to 98.7%, and yield is up to 90.6%.
The utility model has the advantages that
The synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles disclosed by the embodiments of the present invention
Method, has broken the technology prejudice of those skilled in the art, i.e. 2, the 6- dichlor-4-trifluoromethyl aniline of 1mol at least consumes
The HCl of 2mol, the theoretical HCl that need to only consume 1mol, has saved cost, and substantially reduce the generation of " three wastes ".
And this method avoid the diazonium salts that preparation has security risk, improve the safety of entire technique.
This method removes nitrous acid using urea, ammonium sulfite or sodium hydrogensulfite, directly synthesizes 5- amino-using a kettle
3- cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles；Than the existing method using extraction, it is divided to two kettles to synthesize, more supernumerary segment
About cost.
And the purity and receipts of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles that this method obtains
Rate is high, and purity is up to 98.7%, and yield is up to 90.6%.
Therefore, this method have the three wastes are few, highly-safe, production cost is low, high quality, this method be suitble to
Industrialized production.
Detailed description of the invention
Fig. 1 is the route that the prior art synthesizes 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles
Figure；
Fig. 2 is that the embodiment of the present application synthesizes 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles
Route map；
Fig. 3 is the efficient of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles that embodiment 1 generates
Liquid chromatogram；
Fig. 4 is the calculating of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles that embodiment 1 generates
Formula.
Specific embodiment
The present invention will be further described below with reference to examples.Following embodiment is only intended to clearly illustrate this
The performance of invention, and the following examples cannot be limited only to.
Embodiment 1:
Be added in 250mL flask 2,6- dichlor-4-trifluoromethyl aniline 52g, ethyl alcohol 52g, 30% hydrochloric acid 19.4g,
1h is stirred at 30-35 DEG C, forms the ethanol solution of 2,6- dichlor-4-trifluoromethyl aniline salt；
Under room temperature, 2,3- dicyano ethyl propanoate 34.4g, ethyl alcohol 100g, 30% are added in 1000mL four-hole boiling flask
Hydrochloric acid 20.6g obtains the ethanol solution hydrochloride 155g of 2,3- dicyano ethyl propanoate after stirring；
2,6- dichlor-4-trifluoromethyl aniline salt is added dropwise under the conditions of 0-5 DEG C, to 1000mL four-hole boiling flask in control simultaneously
The sodium nitrite in aqueous solution that ethanol solution and 43g concentration are 40%, is added dropwise simultaneously as far as possible, continues to take in 0-5 DEG C of heat preservation 4h
After sample detects 2,6- dichlor-4-trifluoromethyl aniline≤0.5% with HPLC, the urea water that concentration is 40% is added dropwise into reaction solution
Solution to starch potassium iodide paper is tested non-discolouring；
Then ethyl alcohol 21g, 20% ammonium hydroxide 28g is added so that pH >=11 of reaction solution, continue 10-15 DEG C of heat preservation 10h extremely
Reaction terminates；
Add toluene and water extracting and demixing again after depressurizing de- ethyl alcohol, 5- ammonia is obtained after toluene layer freezing and crystallizing, suction filtration, drying
Base -3- cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles.
Wherein, 2,3- dicyano ethyl propanoate and 2, the molar ratio of 6- dichlor-4-trifluoromethyl aniline are 1:1,2,6- bis-
The molar ratio of chloro- 4- 5-trifluoromethylaniline and HCl are 1:1.45, and 2,6- dichlor-4-trifluoromethyl anilines and sodium nitrite rub
You are than being 1:1.1.
It obtains 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles and carries out high performance liquid chromatography point
Analysis, wherein chromatographic condition are as follows: high performance liquid chromatograph: Agilent/Shimadzu；Chromatographic column: Dalian Erie spy Hypersil
ODS2,4.6mm × 250mm, 5 μm；Mobile phase: methanol+acetonitrile+water=50+15+35 (V/V)；Flow velocity: 1.0mL/min；Wavelength:
220nm；Sample volume: 5 μ L；Runing time: 20min.
Specific steps are as follows:
Standard specimen solution: 40.0mg 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles standard is weighed
Product are placed in 100mL volumetric flask, are dissolved with methanol and be diluted to scale.
Sample solution: 40.0mg 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles sample is weighed
Product are placed in 100mL volumetric flask, are dissolved with methanol and be diluted to scale.
Under the operating conditions described above, after instrument stabilizer, 3 needle standard specimen solutions are continuously injected into, calculate main peak response
After RSD% is not more than 2.0%, it is measured according to the sequence of standard specimen solution, sample solution, sample solution, standard specimen solution.
The content of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles, carry out by the formula of Fig. 4 based on
It calculates:
Wherein, in formula:
Cu, Cs --- it is respectively the compound concentration (mg/mL) in sample solution and standard specimen solution；
Main peak response corresponding to rs --- standard specimen solution；
Main peak response corresponding to ru --- sample solution；
The content of P --- standard items, %.
Single contaminant content, is calculated as follows:
100×Ai/A；
In formula:
Ai, A --- it is respectively impurity peak area and total peak area in sample solution map under content determination item.
By being calculated: the 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) that the present embodiment obtains
Pyrazoles purity is 98.7%, yield 90.6%.
Embodiment 2:
Be added in 250mL flask 2,6- dichlor-4-trifluoromethyl aniline 78g, ethyl alcohol 78g, 35% hydrochloric acid 20g,
1.5h is stirred at 30-35 DEG C, forms the ethanol solution of 2,6- dichlor-4-trifluoromethyl aniline salt；
Under room temperature, 2,3- dicyano ethyl propanoate 51.6g, ethyl alcohol 150g, 35% are added in 1000mL four-hole boiling flask
Hydrochloric acid 22.4g obtains the ethanol solution hydrochloride 224g of 2,3- dicyano ethyl propanoate after stirring；
2,6- dichlor-4-trifluoromethyl aniline salt is added dropwise under the conditions of 0-5 DEG C, to 1000mL four-hole boiling flask in control simultaneously
The sodium nitrite in aqueous solution that ethanol solution and 62.4g concentration are 45%, is added dropwise simultaneously as far as possible, continues in 0-5 DEG C of heat preservation 2h,
After sampling detects 2,6- dichlor-4-trifluoromethyl aniline≤0.5% with HPLC, the sulfurous that concentration is 35% is added dropwise into reaction solution
Sour aqueous ammonium to starch potassium iodide paper is tested non-discolouring；
Then ethyl alcohol 31.5g, 30% ammonium hydroxide 23g is added, so that pH >=11 of reaction solution, continue in 10-15 DEG C of heat preservation 8h
Terminate to reaction；
Add toluene and water extracting and demixing again after depressurizing de- ethyl alcohol, 5- ammonia is obtained after toluene layer freezing and crystallizing, suction filtration, drying
Base -3- cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles.
Wherein, 2,3- dicyano ethyl propanoate and 2, the molar ratio of 6- dichlor-4-trifluoromethyl aniline are 1:1,2,6- bis-
The molar ratio of chloro- 4- 5-trifluoromethylaniline and HCl are 1:1.2, mole of 2,6- dichlor-4-trifluoromethyl anilines and sodium nitrite
Than for 1:1.2.
By being calculated: the 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) that the present embodiment obtains
Pyrazoles purity is 98.5%, yield 90.2%.
Embodiment 3:
In 500mL flask be added 2,6- dichlor-4-trifluoromethyl aniline 156g, ethyl alcohol 104g, 32% hydrochloric acid
38.8g stirs 1h at 30-35 DEG C, forms the ethanol solution of 2,6- dichlor-4-trifluoromethyl aniline salt；
Under room temperature, 2,3- dicyano ethyl propanoate 103.2g, ethyl alcohol 200g, 32% are added in 2000mL four-hole boiling flask
Hydrochloric acid 38.8g obtains the ethanol solution hydrochloride 342g of 2,3- dicyano ethyl propanoate after stirring；
2,6- dichlor-4-trifluoromethyl aniline salt is added dropwise under the conditions of 0-5 DEG C, to 2000mL four-hole boiling flask in control simultaneously
The sodium nitrite in aqueous solution that ethanol solution and 122.6g concentration are 42%, is added dropwise simultaneously as far as possible, continues to keep the temperature at 0-5 DEG C
12h, after sampling detects 2,6- dichlor-4-trifluoromethyl aniline≤0.5% with HPLC, it is 38% that concentration is added dropwise into reaction solution
Aqueous solution of sodium bisulfite to starch potassium iodide paper is tested non-discolouring；
Then ethyl alcohol 42g, 25% ammonium hydroxide 46g is added, so that pH >=11 of reaction solution, continue to keep the temperature for 24 hours extremely at 10-15 DEG C
Reaction terminates；
Add toluene and water extracting and demixing again after depressurizing de- ethyl alcohol, 5- ammonia is obtained after toluene layer freezing and crystallizing, suction filtration, drying
Base -3- cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles.
Wherein, 2,3- dicyano ethyl propanoate and 2, the molar ratio of 6- dichlor-4-trifluoromethyl aniline are 1:1,2,6- bis-
The molar ratio of chloro- 4- 5-trifluoromethylaniline and HCl are 1:1, the molar ratio of 2,6- dichlor-4-trifluoromethyl anilines and sodium nitrite
For 1:1.1.
By being calculated: the 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) that the present embodiment obtains
Pyrazoles purity is 98.0%, yield 90.0%.
The synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles disclosed by the embodiments of the present invention
Method, has broken the technology prejudice of those skilled in the art, i.e. 2, the 6- dichlor-4-trifluoromethyl aniline of 1mol is theoretically at least
The HCl of 2mol is consumed, the present invention theoretically need to only consume the HCl of 1mol, and actual production also just consumes the HCl of 1.45mol, right
Than actually acid measures 3mol when diazotising in traditional technology, cost is saved, and substantially reduce the generation of " three wastes ".
And this method avoids generating the diazonium salt with security risk, improves the safety of entire technique.
This method removes nitrous acid using urea, ammonium sulfite or sodium hydrogensulfite, directly synthesizes 5- amino-using a kettle
3- cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles；Than the existing method using extraction, it is divided to two kettles to synthesize, more supernumerary segment
About cost.
And the purity and receipts of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles that this method obtains
Rate is high, and purity is up to 98.7%, and yield is up to 90.6%.Purity and yield are higher than existing numerical value reported in the literature.
Therefore, this method have the three wastes are few, highly-safe, production cost is low, high quality, this method be suitble to
Industrialized production.
The above statement is only preferred embodiment of the invention, it is noted that those skilled in the art, not
Under the premise of being detached from the invention design, various modifications and improvements can be made, these also should be regarded as protection of the invention
Within the scope of.
Claims (8)
- The synthetic method of 1.5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles, which is characterized in that packet It includes:S1, at 30-35 DEG C, by 2,6- dichlor-4-trifluoromethyl aniline, HCl and ethyl alcohol mix, obtain the chloro- 4- of 2,6- bis- The ethanol solution of trifluoromethylbenzene amine salt, wherein the molar ratio of HCl and 2,6- dichlor-4-trifluoromethyl aniline is 0.5-0.75；Under room temperature, 2,3- dicyano ethyl propanoate, HCl and ethyl alcohol are mixed, the hydrochloric acid of 2,3- dicyano ethyl propanoate is obtained Ethanol solution, wherein 2,3- dicyano ethyl propanoates and 2, the molar ratio of 6- dichlor-4-trifluoromethyl aniline are 1:1, HCl with The molar ratio of 2,3- dicyano ethyl propanoate is 0.5-0.75；S2, at 0-5 DEG C, into the ethanol solution hydrochloride of 2,3- dicyano ethyl propanoate simultaneously be added dropwise the chloro- 4- trifluoro of 2,6- bis- The ethanol solution and mass concentration of methylbenzene amine salt are the sodium nitrite solution of 40-45%, wherein 2,6- bis- chloro- 4- fluoroforms The molar ratio of base aniline and sodium nitrite is 1:1-1:1.2, obtains reaction solution；S3, the step S2 reaction solution keep the temperature 2-12h at 0-5 DEG C, until reaction solution in 2,6- dichlor-4-trifluoromethyl After aniline≤0.5%, reproducibility reagent is added dropwise into reaction solution to remove excessive nitrous acid in reaction solution, until in reaction solution Nitrous acid is removed completely；S4, at 10-15 DEG C, ammonium hydroxide and ethyl alcohol are added in the step S3 treated reaction solution, so that the pH of reaction solution >=11, keep the temperature 8-24h；S5, post-processing.
- 2. the synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles according to claim 1 Method, which is characterized in that the hydrochloric acid solution that the HCl is 30%-35% from mass concentration.
- 3. the synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles according to claim 1 Method, which is characterized in that in the step S3, sampling detects 2,6- dichlor-4-trifluoromethyl aniline with high performance liquid chromatography ≤ 0.5%.
- 4. the synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles according to claim 1 Method, which is characterized in that in the step S3, the reproducibility reagent be urea, ammonium sulfite or sodium hydrogensulfite in extremely Few one kind.
- 5. the synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles according to claim 4 Method, which is characterized in that the mass concentration of the reproducibility reagent is the solution of 35-40%.
- 6. the synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles according to claim 1 Method, which is characterized in that in the step S3, tested and non-discolouring confirmed in reaction solution with starch potassium iodide paper by sampling Nitrous acid be removed completely.
- 7. the synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles according to claim 1 Method, which is characterized in that in the step S4, the mass concentration of the ammonium hydroxide is 20-30%.
- 8. the synthesis of 5- Amino 3 cyano -1- (2,6- dichlor-4-trifluoromethyl phenyl) pyrazoles according to claim 1 Method, which is characterized in that in the step S5, the post-processing includes:The de- ethyl alcohol of decompression will be passed through by reaction solution after step S4 processing；Toluene is added and water carries out extracting and demixing；Toluene layer solvent is subjected to freezing and crystallizing, later by filtering and drying, obtains the 5- Amino 3 cyano -1- (2,6- Dichlor-4-trifluoromethyl phenyl) pyrazoles.
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