CN106117145A - The preparation method of 5 amino 1 (2,6 dichloro-4,4 trifluoromethyl) 3 cyano pyrazoles - Google Patents
The preparation method of 5 amino 1 (2,6 dichloro-4,4 trifluoromethyl) 3 cyano pyrazoles Download PDFInfo
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
A kind of 5 amino 1 (2 disclosed by the invention, 6 dichloro-4,4 trifluoromethyls) preparation method of 3 cyano pyrazoles, comprise the following steps: 3,4 two chlorobenzotrifluorides and dimethylamine, with sheet alkali as acid binding agent, sodium dithionite and benzyltriethylammoinium chloride are catalyst, react；The 2 chlorine 4 trifluoromethyl N that will obtain, add chlorosulfuric acid, liquid caustic soda and azodiisobutyronitrile and react in N dimethylaniline；2 will obtained, add sulphuric acid nitrosyl and carry out diazo-reaction, add 2 in 6 dichloro-4,4 5-trifluoromethylanilines, 3 dicyano ethyl propanoates carry out coupling reaction, then carry out ring-closure reaction with strong aqua ammonia in aqueous ammonia medium, to obtain final product.The present invention, with sheet alkali as acid binding agent, with sodium dithionite and benzyltriethylammoinium chloride as catalyst, significantly reduces the cost of raw material；With chlorosulfuric acid as chlorinating agent, reducing the requirement to equipment, safety coefficient is improved；Using single solvent toluene as recrystallisation solvent, the recovery solving the later stage is loaded down with trivial details, the problem of operation easier.
Description
Technical field
The present invention relates to 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole field, particularly relate to
A kind of preparation method of 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole.
Background technology
5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole, is called for short pyrazole ring, is containing fluorobenzene pyrazoles
The pesticide intermediate of insecticides.Owing to this insecticides has a good disinsection effect, the advantage such as degradable, therefore pyrazole ring is subject to
To extensive concern.
The most conventional preparation method is first to synthesize 2-chloro-4-trifluoromethyl-DMA, resynthesis 2,6-bis-
Chloro-4-5-trifluoromethylaniline；Finally, with concentrated sulphuric acid, sodium nitrite and 2,6-dichlor-4-trifluoromethyl aniline is at glacial acetic acid solvent
Middle generation diazol, then with 2,3-dicyano ethyl propanoate is esterified, and finally occurs to reset cyclisation with strong aqua ammonia in aqueous ammonia medium
Reaction obtains product.But, said method existing the part prices of raw materials higher, safety coefficient is on the low side, is not easy to on-the-spot behaviour
Make, the problems such as waste water, solid waste amount are big, not only increase production cost, and with the tightest safe and environment-friendly management shape
Gesture does not matches that.
Summary of the invention
In view of this, the present invention provides a kind of 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole
Preparation method, the method safety is high, convenient to operate, and the three industrial wastes of generation are few, low in raw material price, and production cost is low.
The technical scheme is that and be achieved in that:
The preparation method of a kind of 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole, including following
Step:
A) with 3,4-bis-chlorobenzotrifluoride and dimethylamine are raw material, with sheet alkali as acid binding agent, with sodium dithionite and benzyl
TEBA is catalyst, obtains 2-chloro-4-trifluoromethyl-DMA；
B) the 2-chloro-4-trifluoromethyl-DMA obtained by step a) adds chlorosulfuric acid, liquid caustic soda, azo
Bis-isobutyronitrile is catalyst, obtains 2,6-dichlor-4-trifluoromethyl aniline；
C) the 2,6-dichlor-4-trifluoromethyl aniline that step b) obtains is joined that to carry out diazotising in sulphuric acid nitrosyl anti-
Should, adding 2,3-dicyano ethyl propanoate carries out coupling reaction, then carries out ring-closure reaction with strong aqua ammonia in aqueous ammonia medium, i.e.
?.
Preferably, step a) particularly as follows:
Under vacuum state, input 3 in autoclave, 4-bis-chlorobenzotrifluoride, add sheet alkali, even two sulfurous while stirring
Acid sodium, benzyltriethylammoinium chloride；After adding, close vacuum, add dimethylamine, react and get final product.
Preferably,
In step a), reaction temperature is 100～180 DEG C, and reaction pressure is 1.0～2.6MPa, and reaction end is that reaction terminates
The mass ratio of front described 3,4-bis-chlorobenzotrifluoride described 3,4-bis-chlorobenzotrifluoride front with reaction is less than 1%；Described dimethylamine
Mass concentration be 35～45%；Described 3,4-bis-the parts by weight of chlorobenzotrifluoride be 80～120 parts, the weight of described alkali
Number is 10～20 parts, and the parts by weight of described sodium dithionite are 1～4 part, the weight of described benzyltriethylammoinium chloride
Number is 0.1～0.3 part, and the parts by weight of described dimethylamine are 150～180 parts.
Preferably, step b) particularly as follows:
B1) in chlorination tank, be sequentially added into dichloroethanes, 2-chloro-4-trifluoromethyl-N that step a) obtains, N-dimethyl
Aniline, chlorosulfuric acid, reaction is until the content of 2-chloro-4-trifluoromethyl-DMA is less than 3%；
B2) again to step b1) solution that obtains is sequentially added into azodiisobutyronitrile, chlorosulfuric acid, reaction is until monochlor(in)ate
The content of thing is not higher than 3%；
B3) by step b2) solution that obtains sloughs dichloroethanes, and it is transferred to alkaline hydrolysis still, is sequentially added into water and liquid caustic soda, reaction
Obtain.
Preferably, step b1) described in 2-chloro-4-trifluoromethyl-DMA be 25～35 DEG C in temperature
Under the conditions of be slowly added dropwise, described chlorosulfuric acid is slowly added dropwise under conditions of temperature is 30～50 DEG C；After dripping, temperature is raised to 45
～55 DEG C reacted；The mass concentration of described dichloroethanes is >=99%；The parts by weight of described dichloroethanes be 400～
500 parts, the parts by weight of described chlorosulfuric acid are 80～120 parts.
Preferably, step b2) particularly as follows:
B21) under conditions of temperature is 30～50 DEG C, add azodiisobutyronitrile, be slowly added dropwise chlorosulfuric acid；Described azo
The parts by weight of bis-isobutyronitrile are 1～2 part, and the parts by weight of described chlorosulfuric acid are 80～120 parts；
B22) under conditions of temperature is 35～55 DEG C, add azodiisobutyronitrile, be slowly added dropwise chlorosulfuric acid；Drip
After be warming up to 55～65 DEG C, reaction until the content of monochloride is not higher than 3%；The parts by weight of described azodiisobutyronitrile are
1～2 part, the parts by weight of described chlorosulfuric acid are 100～120 parts.
Preferably, step b3) particularly as follows:
B31) under conditions of temperature is 60～90 DEG C, dichloroethanes is sloughed；
B32) under conditions of temperature is 25～35 DEG C, more slowly drip；Below 60 DEG C, instill liquid caustic soda again after dripping off, adjust
The pH value of whole solution is not less than 12；It is warmed up to 80～90 DEG C again, insulation reaction and get final product；The mass concentration of described liquid caustic soda be 25～
35%；The parts by weight of described water are 80～140 parts, and the parts by weight of described liquid caustic soda are 180～220 parts.
Preferably, step c) particularly as follows:
C1) in diazotising still, 2,6-dichlor-4-trifluoromethyl aniline, the ice that sulphuric acid nitrosyl, step b) obtain is added
Acetic acid, carries out diazo-reaction；
C2) 2 are added at condensation kettle, 3-dicyano ethyl propanoate, glacial acetic acid and step c1) diazonium salt solution that obtains, enters
Row coupling reaction；
C3) to step c2) the condensation solution that obtains is layered, lower floor's oil reservoir and extract upper aqueous layer institute with dichloroethanes
The extract obtained mixes；
C4) by step c3) solution that obtains adds ammonia, regulation pH value of solution, 8～9, separates water layer；Add ammonia
Water, regulation pH value of solution 11 and more than, carry out ring-closure reaction；Reaction terminates rear branch vibration layer, and gained oil reservoir sloughs dichloroethanes,
Add toluene to dissolve, crystallize, to obtain final product.
Preferably, the temperature of described diazo-reaction and described ring-closure reaction is room temperature, and the temperature of described coupling reaction is
15～25 DEG C；Step c1) described in the addition temperature of ammonia be 10～20 DEG C, step c2) described in the addition temperature of ammonia be 5
～15 DEG C；Described slough dichloroethanes be temperature be 35～65 DEG C, vacuum is more than 0.09MPa；Described solution temperature is 55
～65 DEG C, described crystallization temperature is 0～10 DEG C；Step c1) and step c2) described in the mass concentration of glacial acetic acid be >=98%,
The mass concentration of described 2,3-dicyano ethyl propanoate is >=99%；Step c3) described in the mass concentration of dichloroethanes be >=
99%；Step c4) in the mass concentration of described ammonia of twice addition be 25～28%, the mass concentration of described toluene is >=
99%；The parts by weight of described sulphuric acid nitrosyl are 50～65 parts, step c1) described in the parts by weight of glacial acetic acid be 160～
200 parts, the parts by weight of described 2,3-dicyano ethyl propanoate are 50～70 parts, step c2) described in the weight portion of glacial acetic acid
Number is 200～250 parts, and the parts by weight of described dichloroethanes are 800～1200 parts, step c4) in add for the first time described
The parts by weight of ammonia are 110～120 parts, and the parts by weight of the described ammonia that second time adds are 80～90 parts, described toluene
Parts by weight be 120～130 parts.
The preparation method of 5-amino-1-(2,6-dichlor-4-trifluoromethyl the phenyl)-3-cyano pyrazole that the present invention provides,
With sheet alkali as acid binding agent, not in use by the potassium carbonate that price is high；With sodium dithionite and benzyltriethylammoinium chloride for catalysis
Agent, not in use by the potassium iodide that price is high, thus significantly reduces the cost of raw material；With chlorosulfuric acid as chlorinating agent, no longer make
With the chlorine of hypertoxicity, reducing the requirement to equipment, safety coefficient is improved；Use single solvent toluene as crystallization
Solvent, not in use by the mixed solvent of toluene, petroleum ether, normal hexane etc., the recovery solving the later stage is loaded down with trivial details, asking of operation easier
Topic, improves recycled solvent rate, effectively reduces production cost.
Detailed description of the invention
The invention discloses the preparation side of a kind of 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole
Method, those skilled in the art can use for reference present disclosure, is suitably modified technological parameter and realizes.Special needs to be pointed out is, described
Similar replacement and change apparent to those skilled in the art, they are considered as being included in the present invention.This
The method and quoting of invention is described by preferred embodiment, and related personnel substantially can be without departing from the present invention
In appearance, spirit and scope, method described herein and application it is modified or suitably changes and combine, realizing and apply this
Inventive technique.
The preparation method of a kind of 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole, including following
Step:
A) with 3,4-bis-chlorobenzotrifluoride and dimethylamine are raw material, with sheet alkali as acid binding agent, with sodium dithionite and benzyl
TEBA is catalyst, obtains 2-chloro-4-trifluoromethyl-DMA；
B) the 2-chloro-4-trifluoromethyl-DMA obtained by step a) adds chlorosulfuric acid, liquid caustic soda, azo
Bis-isobutyronitrile is catalyst, obtains 2,6-dichlor-4-trifluoromethyl aniline；
C) the 2,6-dichlor-4-trifluoromethyl aniline that step b) obtains is joined that to carry out diazotising in sulphuric acid nitrosyl anti-
Should, adding 2,3-dicyano ethyl propanoate carries out coupling reaction, then carries out ring-closure reaction with strong aqua ammonia in aqueous ammonia medium, i.e.
?.
The raw material that the present invention uses is cheap and easy to get, reduces production cost；And the method safety is high, it is simple to operation.
In the present invention, with 3,4-bis-chlorobenzotrifluoride and dimethylamine are raw material, with sheet alkali as acid binding agent, with even two sulfurous
Acid sodium and benzyltriethylammoinium chloride are catalyst, obtain 2-chloro-4-trifluoromethyl-DMA.Wherein, acid binding agent
Being become cheap sheet alkali from the potassium carbonate that original price is high, catalyst is become even two sulfurous from the potassium iodide that original price is high
Acid sodium and benzyltriethylammoinium chloride, thus significantly reduce the cost of raw material.In an embodiment of the present invention, vacuum state
Under, input 3 in autoclave, 4-bis-chlorobenzotrifluoride, add sheet alkali and sodium dithionite, benzyl triethyl ammonium while stirring
Ammonium chloride；After adding, close vacuum, add dimethylamine, react and get final product.
It should be noted that the reaction end of above-mentioned reaction is reacted 3,3 before 4-bis-chlorobenzotrifluoride and reaction,
The mass ratio of 4-bis-chlorobenzotrifluoride is not higher than 1%.
Wherein, reaction needs to carry out reclaiming and refining after terminating, and this process is: slowly open height when pressure is 0.4MPa
Press the bottom valve of still or deeply intubate valve, transferring the material into washing kettle, react remaining dimethylamine gas and condensed by condenser
And enter two grades of water absorption systems absorptions；Material is layered in washing kettle, and water layer goes to water absorption system to be continued as absorbing water
The dimethylamine condensed out during absorption lower approving and forwarding material, detection dimethylamine content is also applied to down criticize；Oil reservoir use water washing two
Secondary, intermediate layer enters overflow tank and is recycled to down in batch washing, and the bed of material distills under the fine vacuum of more than 0.098MPa, receives 125
～the main distillate fraction of 140 DEG C, it being product, front-end volatiles receive and are applied in lower batch reaction to front-end volatiles reception tank, and every 5 batches of distillations are arranged
Slag once, processes as danger is useless.
Owing to dimethylamine is highly soluble in water, after the present invention uses condensation, multi-level water absorption system reclaims remaining dimethylamine gas
Body so that the waste gas entering blow-down pipe is minimum, and using the layering water layer containing residue dimethylamine liquid as absorbing under water absorption
The dimethylamine gas criticized is applied mechanically so that dimethylamine consumes and waste water, exhausted air quantity significantly reduce, and effectively reduces and produces into
Basis and environmental protection pressure；After completion of the reaction, the present invention utilizes reactor overbottom pressure to turn material, compares and lets out in common process to normal pressure recycling
The methods such as gravity, compressed nitrogen, vacuum, transfering material pump turn material, decrease single batch of time and energy resource consumption, are particularly suitable for platform knot
The process units of structure；The present invention when washing layering by the intermediate layer centralized recovery containing partial material, will when decompression distillation
Front-end volatiles containing partial material are collected and are applied in lower batch of material, distill complete residual liquid and stay in still, concentrate slagging for every 5 batches,
Therefore, the present invention is more abundant to the collection of raw material and product, effectively prevent the manual operation impact on producing result, removes
Outside reducing that danger is useless and producing, actual production obtains the most single batch of output and economic benefit.
In the present invention, in 2-chloro-4-trifluoromethyl-DMA step a) obtained add chlorosulfuric acid,
Liquid caustic soda, azodiisobutyronitrile is catalyst, obtains 2,6-dichlor-4-trifluoromethyl aniline.The chlorinating agent sulfonyl that the present invention uses
Chlorine instead of chlorine of the prior art, and chlorine belongs to severe toxicity gas, very big to harm, and chlorine once meets
Water, will be greatly increased the corrosivity of equipment, and the production accident that reality causes because of chlorine gas leakage in producing can be found everywhere.Therefore
Use chlorine to necessarily require equipment to have fabulous sealing property, this adds increased equipment investment, the technical ability water to operator
Put down and it is also proposed high requirement.The present invention uses chlorosulfuric acid as chlorinating agent, it is to avoid this problem, and safety obtains guarantor
Barrier.
In an embodiment of the present invention, step b) is particularly as follows: b1) in chlorination tank, it is sequentially added into dichloroethanes, step a)
2-chloro-4-trifluoromethyl-DMA of obtaining, chlorosulfuric acid, reaction is until 2-chloro-4-trifluoromethyl-N, N-diformazan
The content of base aniline is less than 3%；B2) again to step b1) solution that obtains is sequentially added into azodiisobutyronitrile, chlorosulfuric acid, instead
Should be until the content of monochloride be not higher than 3%；B3) by step b2) solution that obtains sloughs dichloroethanes, is transferred to alkaline hydrolysis
Still, is sequentially added into water and liquid caustic soda, reacts and get final product.
In other embodiments of the invention, step b1) in 2-chloro-4-trifluoromethyl-DMA in temperature
Being slowly added dropwise under conditions of being 25～35 DEG C, chlorosulfuric acid is slowly added dropwise under conditions of temperature is 30～50 DEG C；After dripping, temperature
Degree is raised to 45～55 DEG C and reacts；The mass concentration of dichloroethanes is >=99%；The parts by weight of dichloroethanes be 400～
500 parts, the parts by weight of chlorosulfuric acid are 80～120 parts.Step b2) particularly as follows: b21) under conditions of temperature is 30～50 DEG C,
Add azodiisobutyronitrile, be slowly added dropwise chlorosulfuric acid；The parts by weight of azodiisobutyronitrile are 1～2 part, the weight portion of chlorosulfuric acid
Number is 80～120 parts；B22) under conditions of temperature is 35～55 DEG C, add azodiisobutyronitrile, be slowly added dropwise chlorosulfuric acid；
Being warming up to 55～65 DEG C after dripping, reaction is until the content of monochloride is not higher than 3%；The parts by weight of azodiisobutyronitrile
Being 1～2 part, the parts by weight of chlorosulfuric acid are 100～120 parts；Step b3) particularly as follows: b31) at the bar that temperature is 60～90 DEG C
Dichloroethanes is sloughed under part；B32) under conditions of temperature is 25～35 DEG C, more slowly drip；Drip below 60 DEG C again after dripping off
Entering liquid caustic soda, the pH value adjusting solution is not less than 12；It is warmed up to 80～90 DEG C again, insulation reaction and get final product；The mass concentration of liquid caustic soda is
25～35%；The parts by weight of water are 80～140 parts, and the parts by weight of liquid caustic soda are 180～220 parts.
The present invention uses the method being dividedly in some parts catalyst and chlorinating agent in secondary chlorination, it is to avoid material drastically reacts
The potential safety hazard brought, makes reaction carry out the most simultaneously, compares disposable addition catalyst and chlorination in common process
The method of agent, security performance is improved, and material unit consumption reduces further.
Wherein, reaction needs also exist for refining after terminating, and subtractive process is: stands, lower floor's bed of material and upper aqueous layer is divided into
Steam distillation still, intermediate layer is divided into overflow tank and periodically reclaims, and is warming up to 100 DEG C in steam distillation still, until product-free steam into
Only；Once, the sulfur dioxide and the hydrogen chloride gas that produce in secondary chlorination, precipitation, hydrolysis link absorb+two grades by level Four water
Alkali absorption+absorbent charcoal adsorber absorbs process.The present invention uses level Four water to absorb+two grades of Alkali absorption devices to process generation
Sulfur dioxide and hydrogen chloride gas, on the one hand obtain comparison sufficient tail gas absorption effect, separately with relatively low equipment investment
On the one hand the hydrochloric acid and the sodium sulfite solution that produce are sold as outside by-product, reduce production cost；After alkaline hydrolysis, solution is except by centre
Layer separates its remainder layer outer, water layer is directly entered lower step steam distillation and additionally adds water without in still, and high-boiling components impurity stays
In still is residual, product quality is barely affected, and wastewater flow rate is greatly reduced；The present invention will be containing partial material when alkaline hydrolysis is layered
Intermediate layer centralized recovery, effectively prevent manual operation on produce result impact, except reduce waste water produce in addition to, in reality
Production obtains the most single batch of output and economic benefit.
In the present invention, 2 obtained by step b), 6-dichlor-4-trifluoromethyl aniline joins in sulphuric acid nitrosyl
Row diazo-reaction, adds 2, and 3-dicyano ethyl propanoate carries out coupling reaction, then carries out with strong aqua ammonia in aqueous ammonia medium
Ring-closure reaction, obtains 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole.At embodiments of the invention
In, step c) is particularly as follows: c1) in diazotising still, add sulphuric acid nitrosyl, step b) obtains 2,6-dichlor-4-trifluoromethyl
Aniline, glacial acetic acid, carry out diazo-reaction；C2) 2,3-dicyano ethyl propanoate, glacial acetic acid and step c1 are added at condensation kettle)
The diazonium salt solution obtained, carries out coupling reaction；C3) to step c2) the condensation solution that obtains is layered, lower floor's oil reservoir and use
The extract of dichloroethanes extraction upper aqueous layer gained mixes；C4) by step c3) solution that obtains adds ammonia, adjust
Joint pH value of solution, 8～9, separates water layer；Add ammonia, regulation pH value of solution 11 and more than, carry out ring-closure reaction；Reaction terminates
Rear branch vibration layer, gained oil reservoir is sloughed dichloroethanes, is added toluene and dissolve, crystallize, to obtain final product.In a further embodiment, weight
The temperature of nitridation reaction and ring-closure reaction is room temperature, and the temperature of coupling reaction is 15～25 DEG C；Step c1) in the addition temperature of ammonia
Degree is 10～20 DEG C, step c2) in the addition temperature of ammonia be 5～15 DEG C；Slough dichloroethanes be temperature be 35～65 DEG C, very
Reciprocal of duty cycle is more than 0.09MPa；Solution temperature is 55～65 DEG C, and crystallization temperature is 0～10 DEG C；Step c1) and step c2) in ice vinegar
The mass concentration of acid is >=98%, and the mass concentration of 2,3-dicyano ethyl propanoates is >=99%；Step c3) in dichloroethanes
Mass concentration is >=99%；Step c4) in the mass concentration of ammonia of twice addition be 25～28%, the mass concentration of toluene is
>=99%；The parts by weight of sulphuric acid nitrosyl are 50～65 parts, step c1) in the parts by weight of glacial acetic acid be 160～200 parts,
The parts by weight of 2,3-dicyano ethyl propanoates are 50～70 parts, step c2) in the parts by weight of glacial acetic acid be 200～250 parts,
The parts by weight of dichloroethanes are 800～1200 parts, step c4) in the parts by weight of ammonia that add for the first time be 110～120
Part, the parts by weight of the ammonia that second time adds are 80～90 parts, and the parts by weight of toluene are 120～130 parts.
It should be noted that the preparation method of above-mentioned sulphuric acid nitrosyl is input concentrated sulphuric acid in diazotising still, at 25 DEG C
Instill glacial acetic acid, be cooled to 15 DEG C, at the uniform velocity put into the most ground sodium nitrite, at 20 DEG C, be incubated 2h, to obtain final product.The present invention
Being ground in advance by sodium nitrite, response rate is greatly improved, and its addition relatively traditional method reduces by more than 20%, does not almost have in system
Having unreacted dregs, waste water salinity declines substantially, and reducing production cost also has certain contribution.
In the present invention, use single solvent toluene as recrystallisation solvent, and traditional method uses toluene, petroleum ether, just
The mixed solvent of hexane etc., the recovery in later stage is relatively complicated, needs to be continuously added a certain solvent to correct mixed system
Distribution concentration, use the method for the invention, reduce operation easier, improve recycled solvent rate, effectively reduce
Production cost.
In order to further illustrate the present invention, a kind of 5-amino-1-(2,6-bis-present invention provided below in conjunction with embodiment
Chloro-4-trifluoromethyl) preparation method of-3-cyano pyrazole is described in detail.
Raw material used in following example is commercially available.
Embodiment 1
Under vacuum state, in autoclave, put into 1000kg3,4-bis-chlorobenzotrifluoride, open stirring, then put into 150kg
Sheet alkali and 25kg sodium dithionite, 1.8kg benzyltriethylammoinium chloride, close vacuum, quickly puts into the diformazan of 1800L40%
Amine aqueous solution, is slowly ramped to 160 DEG C, and pressure is 2.0MPa, controls raw material 3, the response rate of 4-bis-chlorobenzotrifluoride, reaction
Finish；Slowly open the autoclave valve to washing kettle after having reacted when pressure is 0.4MPa, transfer the material into washing kettle, instead
Should be condensed and enter two grades of water absorption systems absorptions by condenser by remaining dimethylamine gas；Material is layered in washing kettle,
Water layer goes to water absorption system to be continued to write instructions and transfer the dimethylamine condensed out during material under absorption as absorbing water, detects dimethylamine
Content also is applied to down criticize；Oil reservoir 500L washes twice, and intermediate layer enters overflow tank and is recycled to down in batch washing, and the bed of material exists
Distill under the fine vacuum of more than 0.098MPa, receive the main distillate fraction of 125～140 DEG C, be 2-chloro-4-trifluoromethyl-N, N-bis-
Monomethylaniline., front-end volatiles receive and are applied in lower batch reaction to front-end volatiles reception tank, and every 5 batches of distillation deslagginves are once, useless as danger
Process.
The present embodiment obtains intermediate product 2-chloro-4-trifluoromethyl-DMA 1012.8kg, purity
94.3%, yield 92.8%.
Embodiment 2～3
With reference to the method for embodiment 1, changing the addition of dimethylamine, other conditions are same as in Example 1, result such as table 1
Shown in.
The impact that amino-alkylation is reacted by the addition of table 1 dimethylamine
| Dimethylamine amount (L) | Product yield (%) | Purity (%) | |
| Embodiment 2 | 1650 | 91.6 | 94.1 |
| Embodiment 3 | 2000 | 92.7 | 94.3 |
Embodiment 4～5
With reference to the method for embodiment 1, changing amino-alkylation holding temperature, other condition is identical with embodiment 1, acquired results
Such as table 2.
The impact that amino-alkylation is reacted by table 2 temperature
Embodiment 6～7
With reference to the method for embodiment 1, changing amino-alkylation heat preservation pressure, other condition is identical with embodiment 1, acquired results
Such as table 3.
The impact that amino-alkylation is reacted by table 3 pressure
| Heat preservation pressure (MPa) | Product yield (%) | Purity (%) | |
| Embodiment 6 | 1.8 | 92.5 | 94.2 |
| Embodiment 7 | 2.2 | 92.7 | 93.9 |
Embodiment 8
In chlorination tank, put into dichloroethanes 1300L, at 30 DEG C, slowly instill the folding hundred that embodiment 1 prepares
400kg2-chloro-4-trifluoromethyl-DMA, slowly instills chlorosulfuric acid 450kg at 40 DEG C, be warming up to 50 DEG C, reaction
Until raw material 2-chloro-4-trifluoromethyl-DMA content≤3%, reaction terminates；It is cooled to 40 DEG C, adds 6kg even
Nitrogen bis-isobutyronitrile, slowly instills chlorosulfuric acid 350kg, is warming up to 50 DEG C, adds 7kg azodiisobutyronitrile, slowly drip after dripping off
Entering chlorosulfuric acid 400kg, be warming up to 60 DEG C of insulations, reaction is until monochloride content≤3%；Precipitation still is proceeded to after feed liquid is qualified,
It is warming up to 90 DEG C until purifying solvent；Being cooled to 30 DEG C, slowly drip 500kg, to destroy remaining chlorosulfuric acid；By above-mentioned feed liquid
Proceed to alkaline hydrolysis still, below 60 DEG C, instill 30% liquid caustic soda 550L, control pH >=12, then be warmed up to 85 DEG C, react 5h；Stand, will
Lower floor's bed of material and upper aqueous layer are divided into 3000L steam distillation still, and intermediate layer is divided into overflow tank and periodically reclaims, and rise in steam distillation still
Temperature is to 100 DEG C, till product-free steams.
The present embodiment obtains intermediate product 2,6-dichlor-4-trifluoromethyl aniline 415.8kg, and purity is 88.7%, receives
Rate 89.6%.
Embodiment 9～10
With reference to the method for embodiment 8, changing the amount putting into solvent, other condition is identical with embodiment 8, acquired results such as table
4。
The impact on chlorination reaction of table 4 quantity of solvent
| Quantity of solvent (L) | Product yield (%) | Purity (%) | |
| Embodiment 9 | 1150 | 87.8 | 87.2 |
| Embodiment 10 | 1450 | 89.6 | 89.4 |
Embodiment 11～12
With reference to the method for embodiment 8, changing the amount of secondary Disulfur dichloride acyl chlorides, other condition is identical with embodiment 8, and gained is tied
Fruit is such as table 5.
The impact on chlorination reaction of 5 two the sulfuryl chloride chlorine doses of table
| Secondary sulfuryl chloride chlorine dose (kg) | Product yield (%) | Purity (%) | |
| Embodiment 11 | 300 | 85.2 | 83.7 |
| Embodiment 12 | 500 | 89.5 | 87.1 |
Embodiment 13～14
With reference to the method for embodiment 8, changing secondary chlorination holding temperature, other condition is identical with embodiment 8, acquired results
Such as table 6.
The impact on chlorination reaction of 6 two the chlorination holding temperatures of table
| Embodiment | Secondary chlorination holding temperature (DEG C) | Product yield (%) | Purity (%) |
| Embodiment 11 | 55 | 89.3 | 88.7 |
| Embodiment 12 | 65 | 88.8 | 87.1 |
Embodiment 15
In 2000L diazotising still, put into concentrated sulphuric acid 200L, instill glacial acetic acid 250L at 25 DEG C, be cooled to 15 DEG C, at the uniform velocity
Put into the most ground sodium nitrite 100kg, at 20 DEG C, be incubated 2h, obtain sulphuric acid nitrosyl；At 20 DEG C, embodiment 8 is made
Folding hundred 270kg2, the 6-dichlor-4-trifluoromethyl aniline obtained and the mixed solution of 500L glacial acetic acid are added dropwise in sulphuric acid nitrosyl,
Carry out diazo-reaction；190kg2,3-dicyano ethyl propanoate and the mixed solution of 600L glacial acetic acid, fall is added in condensation kettle
Above-mentioned diazonium salt solution, to 20 DEG C, is proceeded to rapidly, in this condensation kettle, carry out coupling reaction by temperature；Add water 1000L, separate lower floor
The bed of material, extracts upper aqueous layer 2400L dichloroethanes three times, merges organic layer and obtains mixed solution, and spent acid is recyclable to be applied mechanically；
25% ammonia 400L is dripped, it is ensured that solution ph, 9, separates upper aqueous layer at 15 DEG C；25% ammonia 300L is dripped, really at 10 DEG C
Protect solution ph 11 and more than, carry out ring-closure reaction at room temperature, be incubated 5h, separate organic layer and proceed to precipitation still, negative pressure
Purifying dichloroethanes, outlet temperature, at 65 DEG C, adds toluene 450L while hot, proceeds to crystallization kettle, be cooled to 5 DEG C of knots after dissolving fully
Crystalline substance, centrifugal, dry, obtain 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole.
The present embodiment obtains 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole dry product 323.8kg,
Purity is 96.6%, yield 83.0%.
Embodiment 16～17
With reference to the method for embodiment 15, change 2, the amount of 3-dicyano ethyl propanoate, other condition is identical with embodiment 15,
Acquired results such as table 7.
The impact on cyclization of the amount of table 7 2,3-dicyano ethyl propanoate
Embodiment 18～19
With reference to the method for embodiment 15, changing the amount of extraction dichloroethanes, other condition is identical with embodiment 15, and gained is tied
Fruit is such as table 8.
The impact on cyclization of the amount of table 8 dichloroethanes
| Dichloroethanes amount (L) | Product yield (%) | Purity (%) | |
| Embodiment 18 | 2100 | 82.2 | 96.4 |
| Embodiment 19 | 2700 | 82.7 | 95.9 |
Embodiment 20～21
With reference to the method for embodiment 15, changing crystallization temperature, other condition is identical with embodiment 15, acquired results such as table 9.
The impact on cyclization of table 9 crystallization temperature
| Crystallization temperature (DEG C) | Product yield (%) | Purity (%) | |
| Embodiment 20 | 0 | 82.8 | 95.7 |
| Embodiment 21 | 10 | 81.3 | 96.6 |
The foregoing is only presently preferred embodiments of the present invention, not in order to limit the present invention, all essences in the present invention
Within god and principle, any modification, equivalent substitution and improvement etc. made, should be included within the scope of the present invention.
Claims (9)
1. the preparation method of 5-amino-1-(2,6-dichlor-4-trifluoromethyl phenyl)-3-cyano pyrazole, it is characterised in that
Comprise the following steps:
A) with 3,4-bis-chlorobenzotrifluoride and dimethylamine are raw material, with sheet alkali as acid binding agent, with sodium dithionite and benzyl three
Ethyl ammonium chloride is catalyst, obtains 2-chloro-4-trifluoromethyl-DMA；
B) adding chlorosulfuric acid, liquid caustic soda in the 2-chloro-4-trifluoromethyl-DMA obtained by step a), azo two is different
Butyronitrile is catalyst, obtains 2,6-dichlor-4-trifluoromethyl aniline；
C) 2 that step b) is obtained, 6-dichlor-4-trifluoromethyl aniline joins and carries out diazo-reaction in sulphuric acid nitrosyl,
Adding 2,3-dicyano ethyl propanoate carries out coupling reaction, then carries out ring-closure reaction with strong aqua ammonia in aqueous ammonia medium, to obtain final product.
2. preparation method as claimed in claim 1, it is characterised in that step a) particularly as follows:
Under vacuum state, input 3 in autoclave, 4-bis-chlorobenzotrifluoride, add sheet alkali, hydrosulfurous acid while stirring
Sodium, benzyltriethylammoinium chloride；After adding, close vacuum, add dimethylamine, react and get final product.
3. preparation method as claimed in claim 2, it is characterised in that in step a), reaction temperature is 100～180 DEG C, reaction
Pressure is 1.0～2.6MPa, and reaction end is that reaction terminates front described 3,4-bis-chlorobenzotrifluoride and reaction front described 3,4-bis-
The mass ratio of chlorobenzotrifluoride is less than 1%；The mass concentration of described dimethylamine is 35～45%；Described 3,4-bis-chlorobenzotrifluoride
Parts by weight be 80～120 parts, the parts by weight of described alkali are 10～20 parts, the parts by weight of described sodium dithionite
Being 1～4 part, the parts by weight of described benzyltriethylammoinium chloride are 0.1～0.3 part, and the parts by weight of described dimethylamine are 150
～180 parts.
4. preparation method as claimed in claim 1, it is characterised in that step b) particularly as follows:
B1) in chlorination tank, be sequentially added into dichloroethanes, 2-chloro-4-trifluoromethyl-N that step a) obtains, accelerine,
Chlorosulfuric acid, reaction is until the content of 2-chloro-4-trifluoromethyl-DMA is less than 3%；
B2) again to step b1) solution that obtains is sequentially added into azodiisobutyronitrile, chlorosulfuric acid, reaction is until monochloride
Content is not higher than 3%；
B3) by step b2) solution that obtains sloughs dichloroethanes, is transferred to alkaline hydrolysis still, is sequentially added into water and liquid caustic soda, and reaction is i.e.
?.
5. preparation method as claimed in claim 4, it is characterised in that step b1) described in 2-chloro-4-trifluoromethyl-N, N-
Dimethylaniline is slowly added dropwise under conditions of temperature is 25～35 DEG C, and described chlorosulfuric acid is under conditions of temperature is 30～50 DEG C
It is slowly added dropwise；After dripping, temperature is raised to 45～55 DEG C and reacts；The mass concentration of described dichloroethanes is >=99%；Institute
The parts by weight stating dichloroethanes are 400～500 parts, and the parts by weight of described chlorosulfuric acid are 80～120 parts.
6. preparation method as claimed in claim 4, it is characterised in that step b2) particularly as follows:
B21) under conditions of temperature is 30～50 DEG C, add azodiisobutyronitrile, be slowly added dropwise chlorosulfuric acid；Described azo two is different
The parts by weight of butyronitrile are 1～2 part, and the parts by weight of described chlorosulfuric acid are 80～120 parts；
B22) under conditions of temperature is 35～55 DEG C, add azodiisobutyronitrile, be slowly added dropwise chlorosulfuric acid；Rise after dripping
Temperature is to 55～65 DEG C, and reaction is until the content of monochloride is not higher than 3%；The parts by weight of described azodiisobutyronitrile are 1～2
Part, the parts by weight of described chlorosulfuric acid are 100～120 parts.
7. preparation method as claimed in claim 4, it is characterised in that step b3) particularly as follows:
B31) under conditions of temperature is 60～90 DEG C, dichloroethanes is sloughed；
B32) under conditions of temperature is 25～35 DEG C, more slowly drip；Below 60 DEG C, instill liquid caustic soda again after dripping off, adjust molten
The pH value of liquid is not less than 12；It is warmed up to 80～90 DEG C again, insulation reaction and get final product；The mass concentration of described liquid caustic soda is 25～35%；
The parts by weight of described water are 80～140 parts, and the parts by weight of described liquid caustic soda are 180～220 parts.
8. preparation method as claimed in claim 1, it is characterised in that step c) particularly as follows:
C1) addition sulphuric acid nitrosyl, step b) obtain in diazotising still 2,6-dichlor-4-trifluoromethyl aniline, glacial acetic acid,
Carry out diazo-reaction；
C2) 2 are added at condensation kettle, 3-dicyano ethyl propanoate, glacial acetic acid and step c1) diazonium salt solution that obtains, carry out idol
Connection reaction；
C3) to step c2) the condensation solution that obtains is layered, lower floor's oil reservoir and with dichloroethanes extraction upper aqueous layer gained
Extract mixes；
C4) by step c3) solution that obtains adds ammonia, regulation pH value of solution, 8～9, separates water layer；Add ammonia, adjust
Joint pH value of solution 11 and more than, carry out ring-closure reaction；Reaction terminates rear branch vibration layer, and gained oil reservoir is sloughed dichloroethanes, then added
Enter toluene to dissolve, crystallize, to obtain final product.
9. preparation method as claimed in claim 8, it is characterised in that described diazo-reaction and the temperature of described ring-closure reaction
For room temperature, the temperature of described coupling reaction is 15～25 DEG C；Step c1) described in the addition temperature of ammonia be 10～20 DEG C, step
Rapid c2) described in the addition temperature of ammonia be 5～15 DEG C；Described slough dichloroethanes be temperature be 35～65 DEG C, vacuum is
More than 0.09MPa；Described solution temperature is 55～65 DEG C, and described crystallization temperature is 0～10 DEG C；Step c1) and step c2) in institute
The mass concentration stating glacial acetic acid is >=98%, and the mass concentration of described 2,3-dicyano ethyl propanoate is >=99%；Step c3) in
The mass concentration of described dichloroethanes is >=99%；Step c4) in the mass concentration of described ammonia of twice addition be 25～
28%, the mass concentration of described toluene is >=99%；The parts by weight of described sulphuric acid nitrosyl are 50～65 parts, step c1) in
The parts by weight of described glacial acetic acid are 160～200 parts, and the parts by weight of described 2,3-dicyano ethyl propanoate are 50～70 parts,
Step c2) described in the parts by weight of glacial acetic acid be 200～250 parts, the parts by weight of described dichloroethanes are 800～1200
Part, step c4) in the parts by weight of described ammonia that add for the first time be 110～120 parts, the described ammonia that second time adds
Parts by weight are 80～90 parts, and the parts by weight of described toluene are 120～130 parts.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN111039792A (en) * | 2019-12-11 | 2020-04-21 | 苏州开元民生科技股份有限公司 | Preparation method of aniline compound |
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