CN101070305B - Process for producing N-phenylpyrazolecarbonitrile - Google Patents
Process for producing N-phenylpyrazolecarbonitrile Download PDFInfo
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- AJVCWPYMADNFBI-HVUXDCMCSA-N C/C=C(\C=C(/C=C)\Cl)/Cl Chemical compound C/C=C(\C=C(/C=C)\Cl)/Cl AJVCWPYMADNFBI-HVUXDCMCSA-N 0.000 description 1
- 0 CC([n](c(N)c1)nc1C#N)=C(C=*)Cl Chemical compound CC([n](c(N)c1)nc1C#N)=C(C=*)Cl 0.000 description 1
- NXDQRCBYYUKEQK-UHFFFAOYSA-N CCOC(C(CC#N)(C#N)N=N)=O Chemical compound CCOC(C(CC#N)(C#N)N=N)=O NXDQRCBYYUKEQK-UHFFFAOYSA-N 0.000 description 1
- ITNMAZSPBLRJLU-UHFFFAOYSA-N Nc(c(Cl)cc(C(F)(F)F)c1)c1Cl Chemical compound Nc(c(Cl)cc(C(F)(F)F)c1)c1Cl ITNMAZSPBLRJLU-UHFFFAOYSA-N 0.000 description 1
- ITNMAZSPBLRJLU-UHFFFAOYSA-O [NH3+]c(c(Cl)cc(C(F)(F)F)c1)c1Cl Chemical compound [NH3+]c(c(Cl)cc(C(F)(F)F)c1)c1Cl ITNMAZSPBLRJLU-UHFFFAOYSA-O 0.000 description 1
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Abstract
This invention is the manufacturing method of a arylpyrazol nitrile. The process includes: firstly synthesize simazine - trifluoromethyl - N, N - xylidine; then resynthesize intermedium 2, 6 - dichloro- 4 - trifluoromethyl aniline; thirdly resynthesize intermedium 2, 3 - dicyan ethyl propionate; lastly takes concentrated sulfuric acid and sodium nitrite as raw material, takes reaction in glacial acetic acid solvent, firstly generate nitrosyl vitriol, then takes reaction with arylamine to generate diazonium salt, proceed esterification with dicyan ester, finally takes rearranging cyclization reaction with strong aqua in ammonia medium, gain product. This invention can restrain forming of outgrowth, advance product content to 98%, yield 90% upwards.
Description
Technical field
The present invention relates to a kind of working method of heterocycle pyrazole compound, particularly a kind of working method of heterogeneous ring compound arylpyrazole nitrile.
Background technology
The arylpyrazole nitrile is the heterocycle pyrazole compound, in fields such as medicine, agricultural chemicals, is widely used, and has development prospect and vitality, receives the extensive concern of domestic and international industry member, scientific circles deeply.It is effective to treatment warm-blooded animal inflammation to have narrated 5-amino-1-phenylpyrazole in the U.S. Pat 3760084, and this compound has hydrogen or low alkyl group on 3; Japanese Patent is clear have been narrated the preparation method of preparation 4-thiocyano pyrazole derivatives and has been used as sterilant with 64-12644; The Lesley of Britain May & Baker Ltd. (GB) Dageham, Essex RMIO 7XS, England. the Roy. the Hatton has then delivered the N-phenyl pyrazole compounds of series of substituted and has found that they have the activity of Arthropodicidal, Plant nematode and worm in 1985; Fluorine worm nitrile, ethiprole are exactly outstanding person wherein, and their structural formula is respectively:
Fluorine worm nitrile ethiprole
On 4 of arylpyrazole nitriles, introduce CF respectively
3SO-and C
2H
5SO-can obtain fluorine worm nitrile, ethiprole, uses through developing for many years, has developed into one type of efficient pesticides of quite being paid close attention to, and its prospect of production is very optimistic, and market potential is huge.Thereby it is of far-reaching significance to develop corresponding intermediates arylpyrazole nitrile.
The chemical name of arylpyrazole nitrile is 1-(2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol, and its structural formula is:
CA registration number: 120068-79-3.Molecular formula: C
11H
5Cl
2F
3N
4Molecular weight: 321.09.
Physico-chemical property: pure article are white solid, 141～142 ℃ of fusing points.Dissolve in methyl alcohol, ethanol, acetone, ethylene dichloride and ETHYLE ACETATE.
Summary of the invention
Technical problem to be solved by this invention is the deficiency to prior art, and the working method of a kind of new, technology advantages of simple, arylpyrazole nitrile that yield is high is provided.
Technology to be solved by this invention is to realize through following technical scheme.The present invention is a kind of working method of arylpyrazole nitrile, is characterized in, its step is following,
(1) midbody 2-chloro-4-trifluoromethyl-N, accelerine synthetic; With 3,4-two chlorobenzotrifluorides and n n dimetylaniline are raw material, are acid binding agent with salt of wormwood, are catalyzer with the cuprous salt, carry out the amino-alkylation reaction, promptly get;
(2) midbody 2,6-dichlor-4-trifluoromethyl aniline synthetic; With 2-chloro-4-trifluoromethyl-N, accelerine be starting raw material and chlorine through the ring chlorination reaction, in the presence of initiator, carry out side-chain chlorination with chlorine more then, after the NaOH hydrolysis promptly gets;
(3) midbody 2,3-dicyano ethyl propanoate synthetic; With sodium cyanide, Paraformaldehyde 96 and ethyl cyanoacetate is starting raw material, and reaction generates 1-hydroxyl-2-cyanopropionate in anhydrous ethanol medium, passes through salify, acidification technique then, promptly gets;
(4) finished product arylpyrazole nitrile is synthetic; With the vitriol oil and Sodium Nitrite is starting raw material, in the Glacial acetic acid min. 99.5 solvent, reacts, and generates nitrosyl sulphuric acid earlier, becomes diazonium salt with arylamine reaction then, carries out esterification with two hydrocyanic esters again, in aqueous ammonia medium, with strong aqua cyclization takes place to reset at last and promptly gets.
Technical problem to be solved by this invention can also further realize through following technical scheme.The working method of above-described a kind of arylpyrazole nitrile is characterized in, the working method of step (1) does,
(1) under 0～10 ℃, in autoclave, drop into 3,4-two chlorobenzotrifluorides, n n dimetylaniline water liquid and change agent, three's weight ratio is 1: (2.0-2.5): (0.01-0.03); Wherein, the concentration of n n dimetylaniline water liquid is 30-50%, starts to stir, and slowly is warming up to 160-180 ℃; Pressure is 20-30kg, after 10-15 hour, and sampling analysis; Treat raw material 3,4-two chlorobenzotrifluorides≤1% is a terminal point, and reaction is finished;
(2) purging valve is opened in slowly cooling, absorbs still with amine and absorbs n n dimetylaniline gas, treats in the still that behind the no pressure, purging valve is closed in autoclave emptying 0.2-1.0 hour, the dimethylamine agueous solution concentration of metering absorption still, and reuse;
(3) autoclave is cooled to 50-70 ℃ of discharging, layering, and oil reservoir is with washing 1-3 time, and the bed of material through 105～110 ℃ of rectification under vacuum collections under the high vacuum and pressure is-fraction product under the 0.098Mp.
Technical problem to be solved by this invention can also further realize through following technical scheme.The working method of above-described a kind of arylpyrazole nitrile is characterized in, the working method of step (1) does,
(1) under 0～10 ℃, in the 1000L autoclave, drops into 200kg3,4-two chlorobenzotrifluorides, 460kg n n dimetylaniline water liquid; Concentration is 40%, and the 4kg catalyzer starts and stirs, and slowly is warming up to 170 ℃; Pressure is 25kg, after 13 hours, and sampling analysis; Treat raw material 3,4-two chlorobenzotrifluorides≤1% is a terminal point, and reaction is finished;
(2) purging valve is opened in slowly cooling, absorbs still with amine and absorbs n n dimetylaniline gas, treats in the still that behind the no pressure, purging valve is closed in autoclave emptying 0.5 hour, the dimethylamine agueous solution concentration of metering absorption still, and reuse;
(3) autoclave is cooled to 60 ℃ of dischargings, layering, and oil reservoir is washed secondary with 200L, and the bed of material collects 105～110 ℃ and pressure through rectification under vacuum under the high vacuum and is-fraction product under the 0.098Mp.
Through midbody 2-chloro-4-trifluoromethyl-N that foregoing invention technology obtains, accelerine product average content is 98.3%, and yield is more than 90%.
Technical problem to be solved by this invention can also further realize through following technical scheme.The working method of above-described a kind of arylpyrazole nitrile is characterized in, the working method of step (2) does,
(1) with 2-chloro-4-trifluoromethyl-N, accelerine and solvent drop in the chlorination tank, feed the drying nitrogen displacement; Constantly stir and be heated to 45～70 ℃, be incubated 5-20 minute, stop logical nitrogen; Switch feeding chlorine, logical chlorine bubbling is 2-6 hour under the constant temperature, sampling analysis; Until 2-chloro-4-trifluoromethyl-N, accelerine raw material≤3%, the ring chlorination finishes;
(2) be warming up to 70～90 ℃ then, evenly drip Diisopropyl azodicarboxylate solution, after isothermal reaction 5-15 hour, sampling analysis, a cl content in reaction mixture≤3% is a terminal point, stops logical chlorine and heating, the gas that reaction produces absorbs with alkali;
(3) above-mentioned reaction mass is extracted into the precipitation still, stir heats up, first air distillation, wait to slough most of solvent after, adopt underpressure distillation again, until purifying solvent;
(4) precipitation is finished, and closes vacuum, and material slowly is cooled to 10-20 ℃, drips water, to destroy excessive chlorine; Finish water, slowly drip the 20-40%NaOH aqueous solution, dropping temperature≤70 ℃; Finish, slowly be warming up to 85～90 ℃, be incubated after 0.5-1.5 hour; Whether detect pH greater than 10, as continuing to add NaOH, continuation insulation 6～7 hours less than 10; During the hydrolysis terminal point needs the control side fixed its 2, the total content of 6-dichlor-4-trifluoromethyl aniline is constant;
(5) hydrolysis finishes standing demix, branch vibration layer, and oil reservoir washs with pure water, and branch vibration layer is put into the steam distillation still with the bed of material, adds pure water, is heated to 90-110 ℃, constantly carries out steam distillation, and product-free steams and is terminal point in still.
Technical problem to be solved by this invention can also further realize through following technical scheme.The working method of above-described a kind of arylpyrazole nitrile is characterized in, the working method of step (2) is that (1) is with 0.35kmol2-chloro-4-trifluoromethyl-N; In the chlorination tank that accelerine and solvent input are 1000 liters, feed the drying nitrogen displacement, constantly stir and be heated to 45～70 ℃, be incubated 10 minutes; Stop logical nitrogen, switch feeding chlorine, logical chlorine bubbling is 4 hours under the constant temperature, sampling analysis; Until 2-chloro-4-trifluoromethyl-N, accelerine raw material≤3%, the ring chlorination finishes;
(2) be warming up to 70～90 ℃ then and evenly drip the Diisopropyl azodicarboxylate solution, isothermal reaction is after 9 hours, sampling analysis; Every separated 1.0h sampling analysis once; A cl content in reaction mixture≤3% is a terminal point, stops logical chlorine and heating, and the gas that reaction produces absorbs with alkali;
(3) above-mentioned reaction mass is extracted into 2000 liters of precipitation stills, stir heats up, first air distillation, wait to slough most of solvent after, adopt underpressure distillation again, until purifying solvent;
(4) precipitation is finished, and closes vacuum, material slowly is cooled to 15 ℃ drips 32kg water, to destroy excessive chlorine; Finish water, slowly drip the 30%NaOH aqueous solution, dropping temperature≤70 ℃ finish; Slowly be warming up to 85～90 ℃, be incubated after 1 hour, detect pH whether greater than 10, as continuing to add the NaOH aqueous solution less than 10; Continue insulation 6～7 hours, the control side decided 2 during the hydrolysis terminal point needed, and the total content of 6-dichlor-4-trifluoromethyl aniline is constant;
(5) hydrolysis finishes standing demix, branch vibration layer, and oil reservoir washs secondary with pure water, each water 160kg; Branch vibration layer is put into the steam distillation still with the bed of material, adds the 160kg pure water; Be heated to 100 ℃, constantly carry out steam distillation, product-free steams and is terminal point in still.
Use technology of the present invention can make midbody 2,6-dichlor-4-trifluoromethyl aniline product average content reaches 96.84%, and yield reaches more than 88.54%.
Technical problem to be solved by this invention can also further realize through following technical scheme.The working method of above-described a kind of arylpyrazole nitrile is characterized in, the working method of step (3) does; (1) absolute ethyl alcohol is put in the condensation still, started and stir, be warming up to 35～40 ℃ under little negative pressure; Once drop into the powdery sodium cyanide, under this temperature, stir, treat that dissolving fully;
(2) slowly cooling slowly adds Paraformaldehyde 96, and reinforced time decision temperature in the kettle finishes under this temperature and drips ethyl cyanoacetate, and the dropping time is 2h ± 10 minute, finishes still under this temperature insulation 6-10 hour;
(3) will expect that suction is equipped with in the acidifying still of Sulfothiorine and water in advance and stir, and open device for absorbing tail gas, cooling remains on and drips the 20-40% concentrated hydrochloric acid under this temperature; Stir until pH=5-7 and continuation, treat that acidifying is complete, under reduced pressure slowly slough aqueous ethanol, the precipitation temperature must not be above 80 ℃; After purifying ethanol, cool to 20-40 ℃, disposable entry and the ethylene dichloride of adding, washing extraction; Stir, leave standstill the phase of deoiling; Water with ethylene dichloride extraction 1-3 time, merges organic phase again, uses water washing then, up to neutrality;
(4) with organic phase suction precipitation still, under vacuum, temperature must not be higher than 80 ℃, purifies the ethylene dichloride solvent.
Technical problem to be solved by this invention can also further realize through following technical scheme.The working method of above-described a kind of arylpyrazole nitrile is characterized in, the working method of step (3) does,
(1) the 500kg absolute ethyl alcohol is put in the condensation still, started and stir, be warming up to 35～40 ℃ under little negative pressure, once drop into 40kg powdery sodium cyanide, under this temperature, stirred 2 hours, treat that dissolving fully;
(2) slowly cooling slowly adds the 25kg Paraformaldehyde 96, reinforced time decision temperature in the kettle; Finish under this temperature and to drip the 85kg ethyl cyanoacetate, the dropping time is 2h ± 10 minute, finishes still under this temperature insulation 8 hours; Sampling, chromatogram tracking is until raw material ethyl cyanoacetate≤1%;
(3) will expect that suction is equipped with in the acidifying still of 8kg Sulfothiorine and 50kg water in advance stirs 30min, opens device for absorbing tail gas, and cooling remains on and drips 30% concentrated hydrochloric acid under this temperature; Stir 30min until pH=6 and continuation, treat that acidifying is complete, under reduced pressure slowly slough aqueous ethanol, the precipitation temperature must not be above 80 ℃; After purifying ethanol, cool to 30 ℃, disposable adding 200kg water and 150kg ethylene dichloride; 30min is stirred in the washing extraction, leaves standstill 30min. and divides the phase of deoiling; Water extracts secondary with ethylene dichloride again, merges organic phase, uses water washing then, up to neutrality;
(4) with organic phase suction precipitation still, under vacuum, temperature must not be higher than 80 ℃, purifies the ethylene dichloride solvent, is the cut under the 0.5mmHg at 120-130 ℃ of distillation collection and pressure under the high vacuum unit.
Technical problem to be solved by this invention can also further realize through following technical scheme.The working method of above-described a kind of arylpyrazole nitrile is characterized in, the working method of step (4) does,
(1) vitriol oil that measures is dropped in the diazonium still, start and stir, under 0～10 ℃, slowly drip the Glacial acetic acid min. 99.5 of metering, add Sodium Nitrite in batches, 10～25 ℃ of charge temperatures rise to certain temperature after adding, and are incubated 20-40 minute;
(2) under this temperature, drip 2, the 6-dichlor-4-trifluoromethyl aniline, the dropping time is 20-40min, finishes, and is warmed up to 60-70 ℃, is incubated 2-3 hour, and the reaction end sampling is followed the tracks of, and treats raw material 2, and 6-dichlor-4-trifluoromethyl aniline≤1% is a terminal point;
(3) with above-mentioned feed liquid as early as possible suction be cooled to 5～15 ℃ in advance, be equipped with 2, in the esterifying kettle of the Glacial acetic acid min. 99.5 of 3-dicyano ethyl propanoate and metering, the mixing solutions of water; Carry out esterification, the esterification terminal point determines whether to add raw material 2 through middle control analysis, 3-dicyano-ethyl propionate; Question response finishes, and adds water, tells water; With ethylene dichloride extraction 2-4 time, merge organic layer, spent acid is capable of circulation to be applied mechanically;
(4) the washing organic layer adds ammoniacal liquor to pH>9, tell organic layer, in the suction cyclisation still, add ammoniacal liquor again, carry out rearrangement reaction, obtain light yellow solid through aftertreatment.
Technical problem to be solved by this invention can also further realize through following technical scheme.The working method of above-described a kind of arylpyrazole nitrile is characterized in, the working method of step (4) does,
(1) in the diazonium still with 500 liters of the vitriol oil inputs that measures, start and stir, under 0～10 ℃, slowly drip the Glacial acetic acid min. 99.5 of metering, add Sodium Nitrite in batches, 10～25 ℃ of charge temperatures rise to certain temperature after adding, and are incubated 30 minutes;
(2) Dropwise 5 2.3kg2 under this temperature, the 6-dichlor-4-trifluoromethyl aniline, the dropping time is 30min, finishes, and is warmed up to 65 ℃, is incubated 2.5 hours, and the reaction end sampling is followed the tracks of, and treats raw material 2, and 6-dichlor-4-trifluoromethyl aniline≤1% is a terminal point;
(3) with above-mentioned feed liquid as early as possible suction be cooled to 5～15 ℃ in advance, 2 of 40.7kg is housed, in the esterifying kettle of the Glacial acetic acid min. 99.5 of 3-dicyano ethyl propanoate and metering, the mixing solutions of water, under certain temperature, carry out esterification; The esterification terminal point determines whether to add raw material 2 through middle control analysis, 3-dicyano-ethyl propionate, and question response finishes; Add water 500L, tell water, with ethylene dichloride extraction three times; Each 200 liters, merge organic layer, spent acid is capable of circulation to be applied mechanically;
(4) the washing organic layer adds ammoniacal liquor to pH>9, tell organic layer, in the suction cyclisation still, add ammoniacal liquor again, under certain temperature, carried out rearrangement reaction 6 hours, obtain light yellow solid through aftertreatment.
Compared with prior art, technology of the present invention can suppress the formation of by product effectively, makes product content reach 98%, and yield reaches more than 90%.2-chloro-4-trifluoromethyl-N, accelerine, 2,6-dichlor-4-trifluoromethyl aniline and 2, these three kinds of midbodys that compound is a synthesizing aryl pyrazoles nitrile of 3-dicyano ethyl propanoate, they synthetic has accordingly independently economic worth.The synthetic of arylpyrazole nitrile carried out great improvement to domestic and international existing synthetic route; Each step synthesizes all has different characteristics and innovation; Water liquid method Synthetic 2-chloro-4-trifluoromethyl-N particularly, it is that acid binding agent, cuprous salt are catalyzer that accelerine adopts salt of wormwood; The chlorination Synthetic 2, the 6-dichlor-4-trifluoromethyl aniline is made chlorizating agent with chlorine, adopts new reaction method; In the related diazotization of synthesizing aryl pyrazoles nitrile, the esterification, set up original middle control analysis method, controlled temperature of reaction and time in time, avoided the generation of isomer.
Embodiment
Embodiment 1.A kind of working method of arylpyrazole nitrile, its step is following,
(1) midbody 2-chloro-4-trifluoromethyl-N, accelerine synthetic; With 3,4-two chlorobenzotrifluorides and n n dimetylaniline are raw material, are acid binding agent with salt of wormwood, are catalyzer with the cuprous salt, carry out the amino-alkylation reaction, promptly get;
(2) midbody 2,6-dichlor-4-trifluoromethyl aniline synthetic; With 2-chloro-4-trifluoromethyl-N, accelerine be starting raw material and chlorine through the ring chlorination reaction, in the presence of initiator, carry out side-chain chlorination with chlorine more then, after the NaOH hydrolysis promptly gets;
(3) midbody 2,3-dicyano ethyl propanoate synthetic; With sodium cyanide, Paraformaldehyde 96 and ethyl cyanoacetate is starting raw material, and reaction generates 1-hydroxyl-2-cyanopropionate in anhydrous ethanol medium, passes through salify, acidification technique then, promptly gets;
(4) finished product arylpyrazole nitrile is synthetic; With the vitriol oil and Sodium Nitrite is starting raw material, in the Glacial acetic acid min. 99.5 solvent, reacts, and generates nitrosyl sulphuric acid earlier, becomes diazonium salt with arylamine reaction then, carries out esterification with two hydrocyanic esters again, in aqueous ammonia medium, with strong aqua cyclization takes place to reset at last and promptly gets.
Embodiment 2.Among the embodiment, the working method of step (1) does,
(1) under 0 ℃, in autoclave, drop into 3,4-two chlorobenzotrifluorides, n n dimetylaniline water liquid and change agent, three's weight ratio is 1:2.0:0.01; Wherein, the concentration of n n dimetylaniline water liquid is 30%, starts to stir, and slowly is warming up to 160 ℃; Pressure is 20kg, after 10 hours, and sampling analysis; Treat raw material 3,4-two chlorobenzotrifluorides≤1% is a terminal point, and reaction is finished;
(2) purging valve is opened in slowly cooling, absorbs still with amine and absorbs n n dimetylaniline gas, treats in the still that behind the no pressure, purging valve is closed in autoclave emptying 0.2 hour, the dimethylamine agueous solution concentration of metering absorption still, and reuse;
(3) autoclave is cooled to 50 ℃ of dischargings, layering, and oil reservoir is with washing 1 time, and the bed of material collects 105 ℃ and pressure through rectification under vacuum under the high vacuum and is-fraction product under the 0.098Mp.
Embodiment 3.Among the embodiment, the working method of step (1) does,
(1) under 10 ℃, in autoclave, drop into 3,4-two chlorobenzotrifluorides, n n dimetylaniline water liquid and change agent, three's weight ratio is 1:2.5): 0.03; Wherein, the concentration of n n dimetylaniline water liquid is 50%, starts to stir, and slowly is warming up to 180 ℃; Pressure is 30kg, after 15 hours, and sampling analysis; Treat raw material 3,4-two chlorobenzotrifluorides≤1% is a terminal point, and reaction is finished;
(2) purging valve is opened in slowly cooling, absorbs still with amine and absorbs n n dimetylaniline gas, treats in the still that behind the no pressure, purging valve is closed in autoclave emptying 1.0 hours, the dimethylamine agueous solution concentration of metering absorption still, and reuse;
(3) autoclave is cooled to 70 ℃ of dischargings, layering, and oil reservoir is with washing 3 times, and the bed of material collects 110 ℃ and pressure through rectification under vacuum under the high vacuum and is-fraction product under the 0.098Mp.
Embodiment 4.Among the embodiment, the working method of step (1) does,
(1) under 5 ℃, in the 1000L autoclave, drops into 200kg3,4-two chlorobenzotrifluorides, 460kg n n dimetylaniline water liquid; Concentration is 40%, and the 4kg catalyzer starts and stirs, and slowly is warming up to 170 ℃; Pressure is 25kg, after 13 hours, and sampling analysis; Treat raw material 3,4-two chlorobenzotrifluorides≤1% is a terminal point, and reaction is finished;
(2) purging valve is opened in slowly cooling, absorbs still with amine and absorbs n n dimetylaniline gas, treats in the still that behind the no pressure, purging valve is closed in autoclave emptying 0.5 hour, the dimethylamine agueous solution concentration of metering absorption still, and reuse;
(3) autoclave is cooled to 60 ℃ of dischargings, layering, and oil reservoir is washed secondary with 200L, and the bed of material collects 105～110 ℃ and pressure through rectification under vacuum under the high vacuum and is-fraction product under the 0.098Mp.
Embodiment 5.Among the embodiment, the working method of step (2) does,
(1) with 2-chloro-4-trifluoromethyl-N, accelerine and solvent drop in the chlorination tank, feed the drying nitrogen displacement; Constantly stir and be heated to 45 ℃, be incubated 5 minutes, stop logical nitrogen; Switch feeding chlorine, logical chlorine bubbling is 2 hours under the constant temperature, sampling analysis; Until 2-chloro-4-trifluoromethyl-N, accelerine raw material≤3%, the ring chlorination finishes;
(2) be warming up to 70 ℃ then, evenly drip Diisopropyl azodicarboxylate solution, isothermal reaction is after 5 hours, sampling analysis, and a cl content in reaction mixture≤3% is a terminal point, stops logical chlorine and heating, the gas that reaction produces absorbs with alkali;
(3) above-mentioned reaction mass is extracted into the precipitation still, stir heats up, first air distillation, wait to slough most of solvent after, adopt underpressure distillation again, until purifying solvent;
(4) precipitation is finished, and closes vacuum, and material slowly is cooled to 10 ℃, drips water, to destroy excessive chlorine; Finish water, slowly drip the 20%NaOH aqueous solution, dropping temperature≤70 ℃; Finish, slowly be warming up to 85 ℃, be incubated after 0.5 hour; Whether detect pH greater than 10, as continuing to add NaOH, continuation insulation 6 hours less than 10; During the hydrolysis terminal point needs the control side fixed its 2, the total content of 6-dichlor-4-trifluoromethyl aniline is constant;
(5) hydrolysis finishes standing demix, branch vibration layer, and oil reservoir washs with pure water, and branch vibration layer is put into the steam distillation still with the bed of material, adds pure water, is heated to 90 ℃, constantly carries out steam distillation, and product-free steams and is terminal point in still.
Embodiment 6.Among the embodiment, the working method of step (2) does,
(1) with 2-chloro-4-trifluoromethyl-N, accelerine and solvent drop in the chlorination tank, feed the drying nitrogen displacement; Constantly stir and be heated to 70 ℃, be incubated 20 minutes, stop logical nitrogen; Switch feeding chlorine, logical chlorine bubbling is 6 hours under the constant temperature, sampling analysis; Until 2-chloro-4-trifluoromethyl-N, accelerine raw material≤3%, the ring chlorination finishes;
(2) be warming up to 90 ℃ then, evenly drip Diisopropyl azodicarboxylate solution, isothermal reaction is after 15 hours, sampling analysis, and a cl content in reaction mixture≤3% is a terminal point, stops logical chlorine and heating, the gas that reaction produces absorbs with alkali;
(3) above-mentioned reaction mass is extracted into the precipitation still, stir heats up, first air distillation, wait to slough most of solvent after, adopt underpressure distillation again, until purifying solvent;
(4) precipitation is finished, and closes vacuum, and material slowly is cooled to 20 ℃, drips water, to destroy excessive chlorine; Finish water, slowly drip the 40%NaOH aqueous solution, dropping temperature≤70 ℃; Finish, slowly be warming up to 90 ℃, be incubated after 1.5 hours; Whether detect pH greater than 10, as continuing to add NaOH, continuation insulation 7 hours less than 10; During the hydrolysis terminal point needs the control side fixed its 2, the total content of 6-dichlor-4-trifluoromethyl aniline is constant;
(5) hydrolysis finishes standing demix, branch vibration layer, and oil reservoir washs with pure water, and branch vibration layer is put into the steam distillation still with the bed of material, adds pure water, is heated to 110 ℃, constantly carries out steam distillation, and product-free steams and is terminal point in still.
Embodiment 7.Among the embodiment, the working method of step (2) does,
(1), in the chlorination tank that accelerine and solvent input are 1000 liters, feeds the drying nitrogen displacement with 0.35kmol2-chloro-4-trifluoromethyl-N; Constantly stir and be heated to 45～70 ℃, be incubated 10 minutes, stop logical nitrogen; Switch feeding chlorine, logical chlorine bubbling is 4 hours under the constant temperature, sampling analysis; Until 2-chloro-4-trifluoromethyl-N, accelerine raw material≤3%, the ring chlorination finishes;
(2) be warming up to 70～90 ℃ then and evenly drip the Diisopropyl azodicarboxylate solution, isothermal reaction is after 9 hours, sampling analysis; Every separated 1.0h sampling analysis once; A cl content in reaction mixture≤3% is a terminal point, stops logical chlorine and heating, and the gas that reaction produces absorbs with alkali;
(3) above-mentioned reaction mass is extracted into 2000 liters of precipitation stills, stir heats up, first air distillation, wait to slough most of solvent after, adopt underpressure distillation again, until purifying solvent;
(4) precipitation is finished, and closes vacuum, material slowly is cooled to 15 ℃ drips 32kg water, to destroy excessive chlorine; Finish water, slowly drip the 30%NaOH aqueous solution, dropping temperature≤70 ℃ finish; Slowly be warming up to 85～90 ℃, be incubated after 1 hour, detect pH whether greater than 10, as continuing to add the NaOH aqueous solution less than 10; Continue insulation 6～7 hours, the control side decided 2 during the hydrolysis terminal point needed, and the total content of 6-dichlor-4-trifluoromethyl aniline is constant;
(5) hydrolysis finishes standing demix, branch vibration layer, and oil reservoir washs secondary with pure water, each water 160kg; Branch vibration layer is put into the steam distillation still with the bed of material, adds the 160kg pure water; Be heated to 100 ℃, constantly carry out steam distillation, product-free steams and is terminal point in still.
Embodiment 8.Among the embodiment, the working method of step (3) does,
(1) absolute ethyl alcohol is put in the condensation still, started and stir, be warming up to 35 ℃ under little negative pressure, once drop into the powdery sodium cyanide, under this temperature, stir, treat that dissolving fully;
(2) slowly cooling slowly adds Paraformaldehyde 96, and reinforced time decision temperature in the kettle finishes under this temperature and drips ethyl cyanoacetate, and the dropping time is 2h ± 10 minute, finishes still under this temperature insulation 6 hours;
(3) will expect that suction is equipped with in the acidifying still of Sulfothiorine and water in advance and stir, and open device for absorbing tail gas, cooling remains on and drips 20% concentrated hydrochloric acid under this temperature; Stir until pH=5 and continuation, treat that acidifying is complete, under reduced pressure slowly slough aqueous ethanol, the precipitation temperature must not be above 80 ℃; After purifying ethanol, cool to 20 ℃, disposable entry and the ethylene dichloride of adding, washing extraction; Stir, leave standstill the phase of deoiling; Water with ethylene dichloride extraction 1 time, merges organic phase again, uses water washing then, up to neutrality;
(4) with organic phase suction precipitation still, under vacuum, temperature must not be higher than 80 ℃, purifies the ethylene dichloride solvent.
Embodiment 9.Among the embodiment, the working method of step (3) does,
(1) absolute ethyl alcohol is put in the condensation still, started and stir, be warming up to 40 ℃ under little negative pressure, once drop into the powdery sodium cyanide, under this temperature, stir, treat that dissolving fully;
(2) slowly cooling slowly adds Paraformaldehyde 96, and reinforced time decision temperature in the kettle finishes under this temperature and drips ethyl cyanoacetate, and the dropping time is 2h ± 10 minute, finishes still under this temperature insulation 10 hours;
(3) will expect that suction is equipped with in the acidifying still of Sulfothiorine and water in advance and stir, and open device for absorbing tail gas, cooling remains on and drips 40% concentrated hydrochloric acid under this temperature; Stir until pH=7 and continuation, treat that acidifying is complete, under reduced pressure slowly slough aqueous ethanol, the precipitation temperature must not be above 80 ℃; After purifying ethanol, cool to 40 ℃, disposable entry and the ethylene dichloride of adding, washing extraction; Stir, leave standstill the phase of deoiling; Water with ethylene dichloride extraction 3 times, merges organic phase again, uses water washing then, up to neutrality;
(4) with organic phase suction precipitation still, under vacuum, temperature must not be higher than 80 ℃, purifies the ethylene dichloride solvent.
Embodiment 10.Among the embodiment, the working method of step (3) does,
(1) the 500kg absolute ethyl alcohol is put in the condensation still, started and stir, be warming up to 35～40 ℃ under little negative pressure, once drop into 40kg powdery sodium cyanide, under this temperature, stirred 2 hours, treat that dissolving fully;
(2) slowly cooling slowly adds the 25kg Paraformaldehyde 96, reinforced time decision temperature in the kettle; Finish under this temperature and to drip the 85kg ethyl cyanoacetate, the dropping time is 2h ± 10 minute, finishes still under this temperature insulation 8 hours; Sampling, chromatogram tracking is until raw material ethyl cyanoacetate≤1%;
(3) will expect that suction is equipped with in the acidifying still of 8kg Sulfothiorine and 50kg water in advance stirs 30min, opens device for absorbing tail gas, and cooling remains on and drips 30% concentrated hydrochloric acid under this temperature; Stir 30min until pH=6 and continuation, treat that acidifying is complete, under reduced pressure slowly slough aqueous ethanol, the precipitation temperature must not be above 80 ℃; After purifying ethanol, cool to 30 ℃, disposable adding 200kg water and 150kg ethylene dichloride; 30min is stirred in the washing extraction, leaves standstill 30min. and divides the phase of deoiling; Water extracts secondary with ethylene dichloride again, merges organic phase, uses water washing then, up to neutrality;
(4) with organic phase suction precipitation still, under vacuum, temperature must not be higher than 80 ℃, purifies the ethylene dichloride solvent, is the cut under the 0.5mmHg at 120-130 ℃ of distillation collection and pressure under the high vacuum unit.
Embodiment 11.Among the embodiment, the working method of step (4) does,
(1) vitriol oil that measures is dropped in the diazonium still, start and stir, under 0 ℃, slowly drip the Glacial acetic acid min. 99.5 of metering, add Sodium Nitrite in batches, 10 ℃ of charge temperatures rise to certain temperature after adding, and are incubated 20 minutes;
(2) under this temperature, drip 2, the 6-dichlor-4-trifluoromethyl aniline, the dropping time is 20min, finishes, and is warmed up to 60 ℃, is incubated 2 hours, and the reaction end sampling is followed the tracks of, and treats raw material 2, and 6-dichlor-4-trifluoromethyl aniline≤1% is a terminal point;
(3) with above-mentioned feed liquid as early as possible suction be cooled to 5 ℃ in advance, be equipped with 2, in the esterifying kettle of the Glacial acetic acid min. 99.5 of 3-dicyano ethyl propanoate and metering, the mixing solutions of water; Carry out esterification, the esterification terminal point determines whether to add raw material 2 through middle control analysis, 3-dicyano-ethyl propionate; Question response finishes, and adds water, tells water; With ethylene dichloride extraction 2 times, merge organic layer, spent acid is capable of circulation to be applied mechanically;
(4) the washing organic layer adds ammoniacal liquor to pH>9, tell organic layer, in the suction cyclisation still, add ammoniacal liquor again, carry out rearrangement reaction, obtain light yellow solid through aftertreatment.
Embodiment 12.Among the embodiment, the working method of step (4) does,
(1) vitriol oil that measures is dropped in the diazonium still, start and stir, under 10 ℃, slowly drip the Glacial acetic acid min. 99.5 of metering, add Sodium Nitrite in batches, 25 ℃ of charge temperatures rise to certain temperature after adding, and are incubated 40 minutes;
(2) under this temperature, drip 2, the 6-dichlor-4-trifluoromethyl aniline, the dropping time is 40min, finishes, and is warmed up to 70 ℃, is incubated 3 hours, and the reaction end sampling is followed the tracks of, and treats raw material 2, and 6-dichlor-4-trifluoromethyl aniline≤1% is a terminal point;
(3) with above-mentioned feed liquid as early as possible suction be cooled to 15 ℃ in advance, be equipped with 2, in the esterifying kettle of the Glacial acetic acid min. 99.5 of 3-dicyano ethyl propanoate and metering, the mixing solutions of water; Carry out esterification, the esterification terminal point determines whether to add raw material 2 through middle control analysis, 3-dicyano-ethyl propionate; Question response finishes, and adds water, tells water; With ethylene dichloride extraction 4 times, merge organic layer, spent acid is capable of circulation to be applied mechanically;
(4) the washing organic layer adds ammoniacal liquor to pH>9, tell organic layer, in the suction cyclisation still, add ammoniacal liquor again, carry out rearrangement reaction, obtain light yellow solid through aftertreatment.
Embodiment 13.Among the embodiment, the working method of step (4) does,
(1) in the diazonium still with 500 liters of the vitriol oil inputs that measures, start and stir, under 5 ℃, slowly drip the Glacial acetic acid min. 99.5 of metering, add Sodium Nitrite in batches, 15 ℃ of charge temperatures rise to certain temperature after adding, and are incubated 30 minutes;
(2) Dropwise 5 2.3kg2 under this temperature, the 6-dichlor-4-trifluoromethyl aniline, the dropping time is 30min, finishes, and is warmed up to 65 ℃, is incubated 2.5 hours, and the reaction end sampling is followed the tracks of, and treats raw material 2, and 6-dichlor-4-trifluoromethyl aniline≤1% is a terminal point;
(3) with above-mentioned feed liquid as early as possible suction be cooled to 10 ℃ in advance, 2 of 40.7kg is housed, in the esterifying kettle of the Glacial acetic acid min. 99.5 of 3-dicyano ethyl propanoate and metering, the mixing solutions of water, under certain temperature, carry out esterification; The esterification terminal point determines whether to add raw material 2 through middle control analysis, 3-dicyano-ethyl propionate, and question response finishes; Add water 500L, tell water, with ethylene dichloride extraction three times; Each 200 liters, merge organic layer, spent acid is capable of circulation to be applied mechanically;
(4) the washing organic layer adds ammoniacal liquor to pH>9, tell organic layer, in the suction cyclisation still, add ammoniacal liquor again, under certain temperature, carried out rearrangement reaction 6 hours, obtain light yellow solid through aftertreatment.
Embodiment 14.A kind of working method of arylpyrazole nitrile, its step is following,
One, midbody is synthetic
(1) 2-chloro-4-trifluoromethyl-N, accelerine (abbreviation aminate) synthetic
Operational path
The synthetic route of the aminate that we confirm is with 3, and 4-two chlorobenzotrifluorides and n n dimetylaniline are raw material, is acid binding agent with salt of wormwood, is catalyzer with the cuprous salt, under certain temperature, pressure, carries out the operational path of amino-alkylation reaction.
Reaction formula:
Operation steps
Under 0～10 ℃, in the 1000L autoclave, drop into 200kg3,4-two chlorobenzotrifluorides; 460kg n n dimetylaniline water liquid (content 40%) and 4kg catalyzer start and stir; Slowly be warming up to 170 ℃, pressure is 25kg, after 13 hours; Sampling analysis is treated raw material 3, and 4-two chlorobenzotrifluorides≤1% is a terminal point.Reaction is finished, and slowly purging valve is opened in cooling, absorbs still with amine and absorbs n n dimetylaniline gas, treats in the still that behind the no pressure, purging valve is closed in autoclave emptying 0.5 hour.Metering absorbs the dimethylamine agueous solution concentration of still, and reuse.Autoclave is cooled to 60 ℃ of dischargings, layering, oil reservoir is washed secondary with 200L, bed of material rectification under vacuum under high vacuum collect 105～110 ℃/-the fraction product of 0.098Mp.Metering, analysis, calculated yield.The average content of gained aminate is 98.3%, and yield is 90%.
(2) midbody 2,6-dichlor-4-trifluoromethyl aniline (abbreviation arylamine) synthetic
Operational path
Our determined arylamine synthetic route is with 2-chloro-4-trifluoromethyl-N, accelerine be starting raw material and chlorine through the ring chlorination reaction, in the presence of initiator, carry out side-chain chlorination with chlorine more then, after the operational path of NaOH hydrolysis.
Reaction formula:
Operation steps
0.35kmol aminate and solvent dropped in 1000 liters the chlorination tank, feed the drying nitrogen displacement, constantly stir and be heated to 45～70 ℃, be incubated 10 minutes, stop logical nitrogen, switch feeding chlorine, logical chlorine bubbling is 4 hours under the constant temperature.Sampling analysis, until aminate raw material≤3%, the ring chlorination finishes.Then be warming up to 70～90 ℃ and evenly drip Diisopropyl azodicarboxylate (AIBN) solution, behind the isothermal reaction 9h, sampling analysis, every at a distance from the 1.0h sampling analysis once a cl content in reaction mixture≤3% is a terminal point, stops logical chlorine and heating.The gas that reaction produces absorbs with alkali.
Above-mentioned reaction mass is extracted into 2000 liters of precipitation stills, stir heats up, first air distillation, wait to slough most of solvent after, adopt underpressure distillation again, until purifying solvent (can directly apply mechanically).
Precipitation is finished, and closes vacuum, material slowly is cooled to 15 ℃ drips 32kg water, to destroy excessive chlorine.Finish water, slowly drip the 30%NaOH aqueous solution, dropping temperature≤70 ℃ finish; Slowly be warming up to 85～90 ℃, be incubated after 1 hour, whether detect pH 10; As continuing to add NaOH less than 10, continue insulation 6～7 hours, the total content of fixed its arylamine of control side was constant during the hydrolysis terminal point needed.
Hydrolysis finishes standing demix, branch vibration layer, and oil reservoir washs secondary with pure water, each water 160kg; Branch vibration layer is put into the steam distillation still with the bed of material, adds the 160kg pure water; Be heated to 100 ℃, constantly carry out steam distillation, product-free steams and is terminal point in still.Tell product, metering, sampling analysis, calculated yield.
(3) midbody 2,3-dicyano ethyl propanoate (being called for short two hydrocyanic esters) synthetic
Operational path
We adopt 2, the synthetic route of 3-dicyano ethyl propanoate is to be starting raw material with sodium cyanide, Paraformaldehyde 96 and ethyl cyanoacetate, reaction generates 1-hydroxyl-2-cyanopropionate, salify, acidifying operational path then in anhydrous ethanol medium.
Reaction formula:
Operation steps
The 500kg absolute ethyl alcohol is put in the condensation still, started and stir, be warming up to 35～40 ℃ under little negative pressure, once drop into 40kg powdery sodium cyanide, under this temperature, stirred 2 hours, treat that dissolving fully.Slowly cooling slowly adds the 25kg Paraformaldehyde 96, and reinforced time decision temperature in the kettle finishes and under this temperature, drips the 85kg ethyl cyanoacetate, and the dropping time is 2h ± 10 minute, finishes still under this temperature insulation 8 hours.(sampling, chromatogram tracking is until raw material ethyl cyanoacetate≤1%)
Stir 30min with expecting that suction is equipped with in the acidifying still of 8kg Sulfothiorine and 50kg water in advance; Open device for absorbing tail gas, cooling remains on and drips 30% concentrated hydrochloric acid under this temperature; Stir 30min until pH=6 and continuation; Treat that acidifying is complete, under reduced pressure slowly slough aqueous ethanol, the precipitation temperature must not be above 80 ℃.After purifying ethanol, cool to 30 ℃, disposable adding 200kg water and 150kg ethylene dichloride, 30min is stirred in the washing extraction, leaves standstill 30min. and divides the phase of deoiling; Water extracts secondary with ethylene dichloride again.Merge organic phase, use water washing then, up to neutrality.
With organic phase suction precipitation still, under vacuum, temperature must not be higher than 80 ℃, purifies the ethylene dichloride solvent.Cooling emptying, blowing, metering, analytical calculation yield.Wish to get more high-load product, need under the high vacuum unit, distill the cut of collecting 120-130 ℃/0.5mmHg, content can reach more than 98%, yield 75.24%.
Two, product arylpyrazole nitrile is synthetic
Operational path
The synthetic route of the arylpyrazole nitrile that we confirm is to be starting raw material with the vitriol oil and Sodium Nitrite; In the Glacial acetic acid min. 99.5 solvent, react; Generate nitrosyl sulphuric acid earlier; Then become diazonium salt with arylamine reaction, carry out esterification with two hydrocyanic esters again, in aqueous ammonia medium, cyclization takes place to reset at last with strong aqua.
Reaction formula:
Generate in the above-mentioned reaction main in simplified its azo account for 82%, also have 17% to be hydrazone.
Operation steps
In the diazonium still with 500 liters of the vitriol oil inputs that measures, start and stir, under 0～10 ℃, slowly drip the Glacial acetic acid min. 99.5 of metering, add Sodium Nitrite, 10～25 ℃ of charge temperatures in batches.Rise to certain temperature after adding, be incubated 30 minutes.Dropwise 5 2.3kg arylamine under this temperature, the dropping time is 30min, finishes, and is warmed up to 65 ℃, is incubated 2.5 hours, the reaction end sampling is followed the tracks of, and treats that raw material arylamine≤1% is a terminal point.With above-mentioned feed liquid as early as possible suction be cooled to 5～15 ℃ in advance; 2 of 40.7kg is housed; In the esterifying kettle of the Glacial acetic acid min. 99.5 of 3-dicyano ethyl propanoate and metering, the mixing solutions of water; Under certain temperature, carry out esterification, the esterification terminal point determines whether to add raw material 2 through middle control analysis, 3-dicyano-ethyl propionate.Question response finishes, and adds water 500L, tells water, with three times (each 200 liters) of ethylene dichloride extraction, merges organic layer, and spent acid is capable of circulation to be applied mechanically.
The washing organic layer adds ammoniacal liquor to pH>9, tell organic layer, in the suction cyclisation still, add ammoniacal liquor again, under certain temperature, carried out rearrangement reaction 6 hours, obtain light yellow solid through aftertreatment.Get product purity 98.03%, yield 90.61%.
Claims (7)
1. the working method of a 1-(2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol is characterized in that its step is following,
(1) midbody 2-chloro-4-trifluoromethyl-N, accelerine synthetic; With 3,4-two chlorobenzotrifluorides and n n dimetylaniline are raw material, are acid binding agent with salt of wormwood, are catalyzer with the cuprous salt, carry out the amino-alkylation reaction, promptly get;
(2) midbody 2,6-dichlor-4-trifluoromethyl aniline synthetic; With 2-chloro-4-trifluoromethyl-N, accelerine be starting raw material and chlorine through the ring chlorination reaction, in the presence of initiator, carry out side-chain chlorination with chlorine more then, after the NaOH hydrolysis promptly gets;
(3) midbody 2,3-dicyano ethyl propanoate synthetic; With sodium cyanide, Paraformaldehyde 96 and ethyl cyanoacetate is starting raw material, and reaction generates 1-hydroxyl-2-cyanopropionate in anhydrous ethanol medium, passes through salify, acidification technique then, promptly gets;
(4) finished product 1-(2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol is synthetic; With the vitriol oil and Sodium Nitrite is starting raw material; In the Glacial acetic acid min. 99.5 solvent, react, generate nitrosyl sulphuric acid earlier, then with 2; The 6-dichlor-4-trifluoromethyl aniline is reacted into diazonium salt; With 2, the 3-dicyano ethyl propanoate carries out esterification again, in aqueous ammonia medium, with strong aqua cyclization takes place to reset at last and promptly gets.
2. the working method of a kind of 1-according to claim 1 (2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol is characterized in that, the working method of step (2) does,
(1) with 2-chloro-4-trifluoromethyl-N, accelerine and solvent drop in the chlorination tank, feed the drying nitrogen displacement; Constantly stir and be heated to 45～70 ℃, be incubated 5-20 minute, stop logical nitrogen; Switch feeding chlorine, logical chlorine bubbling is 2-6 hour under the constant temperature, sampling analysis; Until 2-chloro-4-trifluoromethyl-N, accelerine raw material≤3%, the ring chlorination finishes;
(2) be warming up to 70～90 ℃ then, evenly drip Diisopropyl azodicarboxylate solution, after isothermal reaction 5-15 hour, sampling analysis, a cl content in reaction mixture≤3% is a terminal point, stops logical chlorine and heating, the gas that reaction produces absorbs with alkali;
(3) above-mentioned reaction mass is extracted into the precipitation still, stir heats up, first air distillation, wait to slough most of solvent after, adopt underpressure distillation again, until purifying solvent;
(4) precipitation is finished, and closes vacuum, and material slowly is cooled to 10-20 ℃, drips water, to destroy excessive chlorine; Finish water, slowly drip the 20-40%NaOH aqueous solution, dropping temperature≤70 ℃; Finish, slowly be warming up to 85～90 ℃, be incubated after 0.5-1.5 hour; Whether detect pH greater than 10, as continuing to add NaOH, continuation insulation 6～7 hours less than 10; During the hydrolysis terminal point needs detection fixed its 2, the total content of 6-dichlor-4-trifluoromethyl aniline is constant;
(5) hydrolysis finishes standing demix, branch vibration layer, and oil reservoir washs with pure water, and branch vibration layer is put into the steam distillation still with the bed of material, adds pure water, is heated to 90-110 ℃, constantly carries out steam distillation, and product-free steams and is terminal point in still.
3. the working method of a kind of 1-according to claim 1 (2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol is characterized in that, the working method of step (2) does,
(1), in the chlorination tank that accelerine and solvent input are 1000 liters, feeds the drying nitrogen displacement with 0.35kmol2-chloro-4-trifluoromethyl-N; Constantly stir and be heated to 45～70 ℃, be incubated 10 minutes, stop logical nitrogen; Switch feeding chlorine, logical chlorine bubbling is 4 hours under the constant temperature, sampling analysis; Until 2-chloro-4-trifluoromethyl-N, accelerine raw material≤3%, the ring chlorination finishes;
(2) be warming up to 70～90 ℃ then and evenly drip the Diisopropyl azodicarboxylate solution, isothermal reaction is after 9 hours, sampling analysis; Every separated 1.0h sampling analysis once; A cl content in reaction mixture≤3% is a terminal point, stops logical chlorine and heating, and the gas that reaction produces absorbs with alkali;
(3) above-mentioned reaction mass is extracted into 2000 liters of precipitation stills, stir heats up, first air distillation, wait to slough most of solvent after, adopt underpressure distillation again, until purifying solvent;
(4) precipitation is finished, and closes vacuum, material slowly is cooled to 15 ℃ drips 32kg water, to destroy excessive chlorine; Finish water, slowly drip the 30%NaOH aqueous solution, dropping temperature≤70 ℃ finish; Slowly be warming up to 85～90 ℃, be incubated after 1 hour, detect pH whether greater than 10, as continuing to add the NaOH aqueous solution less than 10; Continue insulation 6～7 hours, detection decided 2 during the hydrolysis terminal point needed, and the total content of 6-dichlor-4-trifluoromethyl aniline is constant;
(5) hydrolysis finishes standing demix, branch vibration layer, and oil reservoir washs secondary with pure water, each water 160kg; Branch vibration layer is put into the steam distillation still with the bed of material, adds the 160kg pure water; Be heated to 100 ℃, constantly carry out steam distillation, product-free steams and is terminal point in still.
4. the working method of a kind of 1-according to claim 1 (2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol is characterized in that, the working method of step (3) does,
(1) absolute ethyl alcohol is put in the condensation still, started and stir, be warming up to 35～40 ℃ under little negative pressure, once drop into the powdery sodium cyanide, under this temperature, stir, treat that dissolving fully;
(2) slowly cooling slowly adds Paraformaldehyde 96, and reinforced time decision temperature in the kettle finishes under this temperature and drips ethyl cyanoacetate, and the dropping time is 2h ± 10 minute, finishes still under this temperature insulation 6-10 hour;
(3) will expect that suction is equipped with in the acidifying still of Sulfothiorine and water in advance and stir, and open device for absorbing tail gas, cooling remains on and drips the 20-40% concentrated hydrochloric acid under this temperature; Stir until pH=5-7 and continuation, treat that acidifying is complete, under reduced pressure slowly slough aqueous ethanol, the precipitation temperature must not be above 80 ℃; After purifying ethanol, cool to 20-40 ℃, disposable entry and the ethylene dichloride of adding, washing extraction; Stir, leave standstill the phase of deoiling; Water with ethylene dichloride extraction 1-3 time, merges organic phase again, uses water washing then, up to neutrality;
(4) with organic phase suction precipitation still, under vacuum, temperature must not be higher than 80 ℃, purifies the ethylene dichloride solvent.
5. the working method of a kind of 1-according to claim 1 (2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol is characterized in that, the working method of step (3) does,
(1) the 500kg absolute ethyl alcohol is put in the condensation still, started and stir, be warming up to 35～40 ℃ under little negative pressure, once drop into 40kg powdery sodium cyanide, under this temperature, stirred 2 hours, treat that dissolving fully;
(2) slowly cooling slowly adds the 25kg Paraformaldehyde 96, reinforced time decision temperature in the kettle; Finish under this temperature and to drip the 85kg ethyl cyanoacetate, the dropping time is 2h ± 10 minute, finishes still under this temperature insulation 8 hours; Sampling, chromatogram tracking is until raw material ethyl cyanoacetate≤1%;
(3) will expect that suction is equipped with in the acidifying still of 8kg Sulfothiorine and 50kg water in advance stirs 30min, opens device for absorbing tail gas, and cooling remains on and drips 30% concentrated hydrochloric acid under this temperature; Stir 30min until pH=6 and continuation, treat that acidifying is complete, under reduced pressure slowly slough aqueous ethanol, the precipitation temperature must not be above 80 ℃; After purifying ethanol, cool to 30 ℃, disposable adding 200kg water and 150kg ethylene dichloride; 30min is stirred in the washing extraction, leaves standstill 30min. and divides the phase of deoiling; Water extracts secondary with ethylene dichloride again, merges organic phase, uses water washing then, up to neutrality;
(4) with organic phase suction precipitation still, under vacuum, temperature must not be higher than 80 ℃, purifies the ethylene dichloride solvent, is the cut under the 0.5mmHg at 120-130 ℃ of distillation collection and pressure under the high vacuum unit.
6. the working method of a kind of 1-according to claim 1 (2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol is characterized in that, the working method of step (4) does,
(1) vitriol oil that measures is dropped in the diazonium still, start and stir, under 0～10 ℃, slowly drip the Glacial acetic acid min. 99.5 of metering, add Sodium Nitrite in batches, 10～25 ℃ of charge temperatures rise to certain temperature after adding, and are incubated 20-40 minute;
(2) under this temperature, drip 2, the 6-dichlor-4-trifluoromethyl aniline, the dropping time is 20-40min, finishes, and is warmed up to 60-70 ℃, is incubated 2-3 hour, and the reaction end sampling is followed the tracks of, and treats raw material 2, and 6-dichlor-4-trifluoromethyl aniline≤1% is a terminal point;
(3) with above-mentioned feed liquid as early as possible suction be cooled to 5～15 ℃ in advance, be equipped with 2, in the esterifying kettle of the Glacial acetic acid min. 99.5 of 3-dicyano ethyl propanoate and metering, the mixing solutions of water; Carry out esterification, the esterification terminal point determines whether to add raw material 2 through middle control analysis, 3-dicyano-ethyl propionate; Question response finishes, and adds water, tells water; With ethylene dichloride extraction 2-4 time, merge organic layer, spent acid is capable of circulation to be applied mechanically;
(4) the washing organic layer adds ammoniacal liquor to pH＞9, tells organic layer, in the suction cyclisation still, adds ammoniacal liquor again, carries out rearrangement reaction, obtains light yellow solid through aftertreatment.
7. the working method of a kind of 1-according to claim 1 (2, the 6-dichlor-4-trifluoromethyl) phenyl-3-cyanic acid-5-amino-pyrazol is characterized in that, the working method of step (4) does,
(1) in the diazonium still with 500 liters of the vitriol oil inputs that measures, start and stir, under 0～10 ℃, slowly drip the Glacial acetic acid min. 99.5 of metering, add Sodium Nitrite in batches, 10～25 ℃ of charge temperatures rise to certain temperature after adding, and are incubated 30 minutes;
(2) Dropwise 5 2.3kg2 under this temperature, the 6-dichlor-4-trifluoromethyl aniline, the dropping time is 30min, finishes, and is warmed up to 65 ℃, is incubated 2.5 hours, and the reaction end sampling is followed the tracks of, and treats raw material 2, and 6-dichlor-4-trifluoromethyl aniline≤1% is a terminal point;
(3) with above-mentioned feed liquid as early as possible suction be cooled to 5～15 ℃ in advance, 2 of 40.7kg is housed, in the esterifying kettle of the Glacial acetic acid min. 99.5 of 3-dicyano ethyl propanoate and metering, the mixing solutions of water, under certain temperature, carry out esterification; The esterification terminal point determines whether to add raw material 2 through middle control analysis, 3-dicyano-ethyl propionate, and question response finishes; Add water 500L, tell water, with ethylene dichloride extraction three times; Each 200 liters, merge organic layer, spent acid is capable of circulation to be applied mechanically;
(4) the washing organic layer adds ammoniacal liquor to pH＞9, tells organic layer, in the suction cyclisation still, adds ammoniacal liquor again, under certain temperature, carries out rearrangement reaction 6 hours, obtains light yellow solid through aftertreatment.
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| CN103396366A (en) * | 2013-08-06 | 2013-11-20 | 盐城工学院 | Production method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole |
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| CN103214395B (en) * | 2013-03-26 | 2014-04-30 | 南通市海圣药业有限公司 | Synthesizing process of 2,3-dicyanoethylpropionate |
| CN107098817A (en) * | 2016-02-19 | 2017-08-29 | 江苏托球农化股份有限公司 | 2,6- of one kind dichlor-4-trifluoromethyl anilines lead to chlorine production technology |
| CN106220565A (en) * | 2016-08-17 | 2016-12-14 | 江苏托球农化股份有限公司 | A kind of synthesis technique of 5 amino 3 cyano group 1 (2,6 dichloro-4,4 trifluoromethyl) pyrazoles |
| CN110981806A (en) * | 2019-12-06 | 2020-04-10 | 江苏优普生物化学科技股份有限公司 | Method for synthesizing aryl pyrazole nitrile and byproduct carbonic acid diester |
| CN111039792B (en) * | 2019-12-11 | 2022-10-14 | 苏州开元民生科技股份有限公司 | Preparation method of aniline compound |
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2006
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103396366A (en) * | 2013-08-06 | 2013-11-20 | 盐城工学院 | Production method of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazole |
| CN103396366B (en) * | 2013-08-06 | 2015-12-02 | 盐城工学院 | The production method of 5-Amino 3 cyano-1-(2,6-dichlor-4-trifluoromethyl phenyl) pyrazoles |
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