CN108689875A - A kind of fenhexamid and its synthetic method - Google Patents
A kind of fenhexamid and its synthetic method Download PDFInfo
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- CN108689875A CN108689875A CN201810790163.2A CN201810790163A CN108689875A CN 108689875 A CN108689875 A CN 108689875A CN 201810790163 A CN201810790163 A CN 201810790163A CN 108689875 A CN108689875 A CN 108689875A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/02—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides
- C07C245/06—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings
- C07C245/08—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings with the two nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings, e.g. azobenzene
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/20—Diazonium compounds
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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Abstract
The invention discloses a kind of fenhexamid and its synthetic methods, including following raw material:Aniline, hydrochloric acid, sodium nitrite solution, 2,3- chlorophenesic acids, sodium hydroxide, water, ethyl alcohol, sodium hydrosulfite, 1- methyl cyclohexylpentanoic acid, dichloromethane, n,N-Dimethylformamide, thionyl chloride, ethyl acetate and triethylamine.The content of the fenhexamid of gained of the invention is 98% or more, yield reaches 86~87%, and in fenhexamid building-up process, azo compound reduction generates 2, when bis- chloro- 4- hydroxyanilines of 3-, it is restored using sodium hydrosulfite, the reproducibility of sodium hydrosulfite is strong, fast in alkalescent reduction reaction speed, sodium hydroxide and sodium hydrosulfite are intersected into input, conversion ratio can be made 98% or more, and add sodium hydrosulfite to have sour regurgitation phenomenon, finally pH be made to maintain between 6~7.The working condition of fenhexamid is mild, easy to operate, safe, and total recovery is high, at low cost, is suitable for enterprise scale and produces and apply.
Description
Technical field
The present invention relates to pesticide processing technical fields, and in particular to a kind of fenhexamid and its synthetic method.
Background technology
Fenhexamid is the novel amides systemic fungicide of Bayer A.G's exploitation, to gray mold, sclerotiniose etc.
Prevention it is highly effective, and to other medicaments generate resistance strain it is also effective, without cross-resistance with existing fungicides, mainly
Prevention for including the diseases such as vegetables, grape, fruit tree.Due to its distinctive mechanism of action, in addition to crop safety and favorably
Toxicity data and ecological effect, be that ideal comprehensive evil object administers medication.
In existing fenhexamid synthetic method, the yield of fenhexamid is relatively low, the organic solvent used in building-up process
Toxicity is higher, and safety is poor, and recycling energy consumption is larger, the time is long, causes the production cycle long, and production cost is high, is unfavorable for looking forward to
The large-scale production of industry.
Invention content
For problems of the prior art, the purpose of the present invention is to provide a kind of fenhexamid and its synthesis sides
Method, the content of the fenhexamid is 98% or more, and yield reaches 86~87%, and synthetic method mild condition is easy to operate, safety
Property it is high, total recovery is high, at low cost, is suitable for enterprise scale and produces and apply.
In order to achieve the above object, the present invention is achieved by the following scheme.
(1) a kind of fenhexamid, including following raw material:Aniline, hydrochloric acid, sodium nitrite solution, 2,3- chlorophenesic acids, hydrogen
Sodium oxide molybdena, water, ethyl alcohol, sodium hydrosulfite, 1- methyl cyclohexylpentanoic acid, dichloromethane, n,N-Dimethylformamide, thionyl chloride, acetic acid second
Ester and triethylamine.
Preferably, the dosage of the raw material is:70-90 parts of aniline, 270-290 parts of hydrochloric acid, sodium nitrite solution 110-122
Part, 120-140 parts of 2,3- chlorophenesic acids, 164-171 parts of sodium hydroxide, 950-1150 parts of water, 480-520 parts of ethyl alcohol, sodium hydrosulfite
336-364 parts, 110-130 parts of 1- methyl cyclohexylpentanoic acids, 580-620 parts of dichloromethane, 1-2 parts of n,N-Dimethylformamide, chlorination
70-74 parts of 120-140 parts of sulfoxide, 780-820 parts of ethyl acetate and triethylamine.
It is further preferred that the dosage of the raw material is:80 parts of aniline, 280 parts of hydrochloric acid, 116 parts of sodium nitrite solution, 2,
130 parts of 3- chlorophenesic acids, 167.5 parts of sodium hydroxide, 1050 parts of water, 500 parts of ethyl alcohol, 350 parts of sodium hydrosulfite, 1- methyl cyclohexylpentanoic acids
120 parts, 600 parts of dichloromethane, 1 part of n,N-Dimethylformamide, 130 parts of thionyl chloride, 800 parts of ethyl acetate and triethylamine 72
Part.
(2) a kind of synthetic method of fenhexamid, includes the following steps:
Step 1, hydrochloric acid is added dropwise while stirring into aniline, cools down, is added dropwise to sodium nitrite solution, insulation reaction obtains weight
Nitrogen salt;
Step 2,2,3- chlorophenesic acids, sodium hydroxide and water are mixed, primary to stir, the diazol is added dropwise in cooling,
Secondary agitation, centrifugation, obtains azo compound;
Step 3, second alcohol and water is added into the azo compound, heating intersects sodium hydroxide and guarantor are added in batches successively
Dangerous powder, insulation reaction, negative pressure recycle ethyl alcohol, water and aniline, obtain 2,3-, bis- chloro- 4- hydroxyanilines crude products;To the 2,3-
Two chloro- 4- hydroxyanilines crude products are washed, primary to centrifuge, and are obtained centrifugation object, are recrystallized to the centrifugation object, it is secondary from
The heart, drying, obtains 2,3-, bis- chloro- 4- hydroxyanilines;
Step 4,1- methyl cyclohexylpentanoic acid, dichloromethane and n,N-Dimethylformamide are mixed, back flow reaction, reflux is anti-
Middle dropwise addition thionyl chloride is answered, back flow reaction is continued, normal pressure recycles dichloromethane, and negative pressure recycles thionyl chloride, obtained 1- methyl ring
Formyl chloride;
Step 5, by 2,3-, bis- chloro- 4- hydroxyanilines, 1- methyl ring, formyl chloride and ethyl acetate mix, and reflux is anti-
It answers, triethylamine is added dropwise during back flow reaction, continue back flow reaction, cool down, filter, obtain triethylamine hydrochloride and mother liquor;To institute
It states mother liquor to be decolourized and cleaned, wash, normal pressure recycles ethyl acetate, centrifuges, and drying obtains fenhexamid.
Preferably, in step 1, the temperature of the stirring is 25~40 DEG C, and the rotating speed of stirring is 95 revs/min.
Preferably, in step 1, the time for adding of the hydrochloric acid is 1.5~2 hours.
Preferably, in step 1, the cooling is to be cooled to 0~5 DEG C.
Preferably, in step 1, the temperature of the dropwise addition of the sodium nitrite solution is 0~5 DEG C, the drop of sodium nitrite solution
It is 2.5~3 hours between added-time.
Preferably, in step 1, the mass concentration of the sodium nitrite solution is 40~60%.
Preferably, in step 1, the temperature of the insulation reaction is 0~5 DEG C, and the time of insulation reaction is 1~2 hour.
Preferably, in step 2, the mass ratio of the sodium hydroxide and 2, the 3- chlorophenesic acids is 80:(120-140);
The mass ratio of the water and 2, the 3- chlorophenesic acids is (900-1100):(120-140).
Preferably, in step 2, the rotating speed once stirred is 95 revs/min, and the time once stirred is 1~2 small
When.
Preferably, in step 2, the cooling is to be cooled to-(4~6) DEG C.
Preferably, in step 2, the time for adding of the diazol is 25~35 minutes.
Preferably, in step 2, the temperature of the secondary agitation is 4~6 DEG C, and the rotating speed of secondary agitation is 95 revs/min,
The time of secondary agitation is 25~35 minutes.
Preferably, in step 2, the rotating speed of the centrifugation is 3000~3500rpm, and the time of centrifugation is 8~12 minutes.
Preferably, in step 3, the heating is to be warming up to 40~45 DEG C.
Preferably, in step 3, each point of 7 addition of the sodium hydroxide and sodium hydrosulfite, the amount for the sodium hydroxide being added every time
Identical, the amount for the sodium hydrosulfite being added every time is identical.
Preferably, in step 3, the temperature of the insulation reaction is 40~50 DEG C, and the time of insulation reaction is 4~5 hours.
Preferably, in step 3, the pressure of the negative pressure recycling ethyl alcohol, water and aniline is-(0.085~0.090) MPa,
The temperature that negative pressure recycles ethyl alcohol, water and aniline is 60~65 DEG C, and the time that negative pressure recycles ethyl alcohol, water and aniline is 4~5 hours.
Preferably, in step 3, the washing is according to the following steps:It is added into bis- chloro- 4- hydroxyanilines crude products of 2,3-
Water is warming up to 60~65 DEG C, keeps the temperature 1~1.5 hour, is cooled to 30 DEG C or less.
Preferably, in step 3, the rotating speed once centrifuged be 3000~3500rpm, the time once centrifuged be 8~
12 minutes.
Preferably, in step 3, the recrystallization uses content to be recrystallized for 99% toluene.
It is further preferred that in step 3, the recrystallization uses following operating procedure:Toluene is added into centrifugation object, rises
Temperature keeps the temperature 1~1.5 hour, is cooled to 25 DEG C of following crystallization to 84~86 DEG C.
Preferably, in step 3, the rotating speed of the secondary centrifuging is 3000~3500rpm, time of secondary centrifuging is 8~
12 minutes.
Preferably, in step 3, the temperature of the drying is 65~75 DEG C, and the time of drying is 2.8~3.2 hours.
Preferably, in step 4, the temperature of the back flow reaction is 40~45 DEG C.
Preferably, in step 4, the time for adding of the thionyl chloride is 1.5~2.5 hours.
Preferably, in step 4, the time for continuing back flow reaction is 6~7 hours.
Preferably, in step 4, the temperature of the negative pressure recycling thionyl chloride is 80~85 DEG C, and negative pressure recycles thionyl chloride
Pressure be-(0.085~0.090) MPa, negative pressure recycle thionyl chloride time be 6~7 hours.
Preferably, in step 5, the temperature of the back flow reaction is 78~80 DEG C.
Preferably, in step 5, the time for adding of the triethylamine is 0.4~1 hour.
Preferably, in step 5, the temperature for continuing back flow reaction is 78~80 DEG C, and the time for continuing back flow reaction is 2
~3 hours.
Preferably, in step 5, the cooling is to be cooled to 25 DEG C or less.
Preferably, in step 5, the pressure of the suction filtration is-(0.085~0.090) MPa, and the time of suction filtration is 10 points
Clock.
Preferably, in step 5, the mother liquor is decolourized and is cleaned using activated carbon.
It is further preferred that in step 5, is decolourized and cleaned using following steps to the mother liquor:Add into mother liquor
Enter activated carbon, the back flow reaction 1~1.2 hour under the conditions of 78~80 DEG C, then in the negative pressure item of-(0.085~0.090) MPa
It is filtered 8~12 minutes under part.
Preferably, in step 5, the temperature of the centrifugation is 30~40 DEG C, and the rotating speed of centrifugation is 3000~3500rpm, from
The time of the heart is 8~12 minutes.
Preferably, in step 5, the temperature of the drying is 75~85 DEG C, and the time of drying is 2.8~3.2 hours.
Compared with prior art, beneficial effects of the present invention are:
For the content of the fenhexamid of gained of the invention 98% or more, yield reaches 86~87%, chloro- with 2,3- bis-
4- hydroxyanilines meters.In fenhexamid building-up process, when azo compound reduction generates 2,3-, bis- chloro- 4- hydroxyanilines, adopt
It is restored with sodium hydrosulfite, the reproducibility of sodium hydrosulfite is strong, fast in alkalescent reduction reaction speed, and sodium hydroxide and sodium hydrosulfite are intersected and thrown
Enter, conversion ratio can be made 98% or more, and adding sodium hydrosulfite has sour regurgitation phenomenon, between finally pH being made to maintain 6~7, be not necessarily to
With hydrochloric acid tone pitch.1- methyl ring is obtained in formyl chloride technique in 1- methyl cyclohexylpentanoic acid chlorinations, the dichloromethane conduct of use
Acetic acid second is used during solvent, 2,3- bis- chloro- 4- hydroxyanilines and 1- methyl the ring fenhexamid of formyl chloride synthesis
For ester as solvent, the small toxicity of dichloromethane and ethyl acetate is safe, and low energy consumption for recycling, and recovery time is short.The present invention is
The working condition of fenhexamid is mild, easy to operate, safe, and total recovery is high, at low cost, be suitable for enterprise scale production and
Using.
Specific implementation mode
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
It will be appreciated that the following example is merely to illustrate the present invention, and it is not construed as limiting the scope of the invention.
Embodiment 1
A kind of synthetic method of fenhexamid, includes the following steps:
Step 1, aniline 80kg is added into reaction kettle, jacket refrigerating brine is opened, with 95 revs/min under the conditions of 32 DEG C
Rotating speed stirring, the hydrochloric acid 280kg being added dropwise in head tank is added while stirring, hydrochloric acid drips in 1.5 hours, and hydrochloric acid is added dropwise
0 DEG C is cooled to after complete, the mass concentration being added dropwise under the conditions of 2.5 DEG C in head tank is 50% sodium nitrite solution (58kg nitrous
Sour sodium+58kg water), sodium nitrite solution drips in 2.7 hours, and insulation reaction 1 is small at a temperature of 2.5 DEG C after dripping
When, obtain diazol;Wherein, shown in the synthesis technology of diazol such as formula (1).
Step 2, be added 130kg 2 into synthesis azo kettle, 3- chlorophenesic acids, 80kg sodium hydroxides and 1000kg water (2,
3- chlorophenesic acids, which are dissolved in sodium hydroxide, forms sodium phenolate, while water is as solution), with 95 revs/min of speed one under room temperature
Secondary stirring 1 hour, allowed 2,3- chlorophenesic acids to be dissolved completely in sodium hydroxide solution, is then cooled to -5 DEG C, at 30 minutes
The diazol obtained by step 1 is inside dripped, then under the conditions of 5 DEG C with 95 revs/min of speed secondary agitation 30 minutes, with
The rotating speed of 3300rpm centrifuges 10 minutes, removes sodium-chloride water solution, obtains azo compound.Wherein, the weight of azo compound is about 500kg,
Water content is about 50%, shown in the specific synthesis technology such as formula (2) of azo compound.
Step 3, by the azo compound input reduction kettle obtained by step 2,95% ethyl alcohol 500kg and 50kg water, heating is added
To 40 DEG C, 12.5kg sodium hydroxides are first added and adjust pH value to 10, followed by be added 50kg sodium hydrosulfites (sodium dithionite,
Na2O4S2), 12.5kg sodium hydroxides and 50kg sodium hydrosulfites 7 times is added in repeated overlapping, and insulation reaction 4 is small at this temperature after adding
When, azo compound restores under the action of sodium hydrosulfite generates 2,3-, bis- chloro- 4- hydroxyanilines crude products and aniline.Then it is warming up to
60 DEG C and under -0.087MPa condition of negative pressure recycle ethyl alcohol, water and revert back come aniline, recycling 4 hours it is recyclable about
700kg mixtures.After having recycled, 800kg water is added into 2,3-, bis- chloro- 4- hydroxyanilines crude products, is warming up to 60 DEG C, protects
Temperature 1 hour, cools to 30 DEG C, is once centrifuged 10 minutes with the rotating speed of 3300rpm, obtains 180~200kg centrifugation objects, passes through washing
Remove the impurity such as water-soluble inorganic salt;It uses content to be recrystallized for 99% toluene centrifugation object, organic impurities is removed, is had
Body is:Centrifugation object is put into reaction kettle, 500kg toluene is added, is warming up to 84 DEG C, keeps the temperature 1 hour at this temperature, is cooled to
25 DEG C of crystallizations, with the rotating speed secondary centrifuging 10 minutes of 3300rpm, and dry 3 hours under the conditions of 70 DEG C, it is chloro- to obtain 2,3- bis-
4- hydroxyanilines fine work.Wherein, the weight of 2,3-, bis- chloro- 4- hydroxyanilines fine work is 138~139kg, and content is
98.0%, yield 96%, azo compound reduction generates shown in the concrete technology such as formula (3) of 2,3-, bis- chloro- 4- hydroxyanilines.
Step 4, by the n,N-Dimethylformamide (DMF) of 120kg 1- methyl cyclohexylpentanoic acid, 600kg dichloromethane and 1kg
Catalyst is added in chlorination tank, is warming up to 40 DEG C of back flow reactions, and 130kg thionyl chlorides, chlorination are added dropwise during back flow reaction
Sulfoxide was added at 1.5 hours, continued back flow reaction after being added dropwise to complete 6 hours, the sulfur dioxide and hydrogen chloride that back flow reaction generates
Gas is absorbed using 30% sodium hydroxide buck.After back flow reaction is fully completed, normal pressure recycles dichloromethane (can be with circulating sleeve
With), after dichloromethane has recycled, then excessive chlorination is recycled under conditions of temperature is 80 DEG C, negative pressure is -0.087MPa
Sulfoxide recycles 6 hours, and 1- methyl ring formyl chloride is obtained after having recycled.Wherein, the weight of 1- methyl ring formyl chloride is
134kg, content 98%, yield 98%, 1- methyl cyclohexylpentanoic acid chlorinations obtain the concrete technology such as formula of 1- methyl ring formyl chloride
(4) shown in.
Step 5,2,3-, bis- chloro- 4- hydroxyanilines 120kg, 1- methyl rings formyl chloride is added into finished product kettle
113kg and ethyl acetate 800kg is warming up to 78 DEG C of back flow reactions, and triethylamine 72kg, triethylamine are added dropwise during back flow reaction
Continue back flow reaction 2 hours under the conditions of 78 DEG C after being dripped in 0.7 hour, is cooled to 25 DEG C after reaction ,-
It is filtered 10 minutes under the negative pressure of 0.087MPa, obtains triethylamine hydrochloride and mother liquor.10kg activated carbon (activated carbons are added into mother liquor
For decolourizing and cleaning), the back flow reaction 1 hour under the conditions of 78 DEG C filters 10 minutes under the condition of negative pressure of -0.087MPa,
300kg water is added, ethyl acetate is recycled under the conditions of 78 DEG C of normal pressure, ethyl acetate has been recycled, obtained by recycling for 2.5~3 hours
Product suspend in water, are centrifuged 10 minutes with the rotating speed of 3200rpm under the conditions of 35 DEG C, obtain crude product, and it is small that 3 are dried under the conditions of 80 DEG C
When, obtain fenhexamid.Wherein the weight of fenhexamid is 185~188kg, and content 98%, yield is 90% or more, 2,3-
Shown in the concrete technology such as formula (5) of two chloro- 4- hydroxyanilines and the 1- methyl ring fenhexamid of formyl chloride synthesis.
Embodiment 2
A kind of synthetic method of fenhexamid, includes the following steps:
Step 1, aniline 70kg is added into reaction kettle, jacket refrigerating brine is opened, with 95 revs/min under the conditions of 25 DEG C
Rotating speed stirring, the hydrochloric acid 270kg being added dropwise in head tank is added while stirring, hydrochloric acid drips in 1.7 hours, and hydrochloric acid is added dropwise
0 DEG C is cooled to after complete, the mass concentration being added dropwise under the conditions of 0 DEG C in head tank is 40% sodium nitrite solution 110kg, nitrous acid
Sodium solution drips in 2.5 hours, after dripping at a temperature of 0 DEG C insulation reaction 1.5 hours, obtain diazol.
Step 2, the addition 140kg 2 into synthesis azo kettle, 3- chlorophenesic acids, 80kg sodium hydroxides and 1100kg water, 2,
3- chlorophenesic acids, which are dissolved in sodium hydroxide solution, forms sodium phenolate, while water is as solution, with 95 revs/min of speed under room temperature
The primary stirring of degree 1.5 hours, allows 2,3- chlorophenesic acids to be dissolved completely in sodium hydroxide solution, is then cooled to -6 DEG C,
The diazol obtained by step 1 is dripped in 25 minutes, is then divided with 95 revs/min of speed secondary agitation 35 under the conditions of 4 DEG C
Clock is centrifuged 12 minutes with the rotating speed of 3000rpm, is removed sodium-chloride water solution, is obtained azo compound.
Step 3, by the azo compound input reduction kettle obtained by step 2,95% ethyl alcohol 480kg and 50kg water, heating is added
To 42.5 DEG C, 12kg sodium hydroxides are first added and adjust pH value to 10, followed by be added 48kg sodium hydrosulfites (sodium dithionite,
Na2O4S2), 12.5kg sodium hydroxides and 50kg sodium hydrosulfites 7 times is added in repeated overlapping, and insulation reaction 4 is small at this temperature after adding
When, azo compound restores under the action of sodium hydrosulfite generates 2,3-, bis- chloro- 4- hydroxyanilines crude products and aniline.Then it is warming up to
65 DEG C and under -0.090MPa condition of negative pressure recycle ethyl alcohol, water and revert back come aniline, recycling 4.5 hours it is recyclable about
700kg mixtures.After having recycled, 800kg water is added into 2,3-, bis- chloro- 4- hydroxyanilines crude products, is warming up to 65 DEG C, protects
Temperature 1.2 hours, cools to 29 DEG C, is once centrifuged 8 minutes with the rotating speed of 3500rpm, obtains 180~200kg centrifugation objects, passes through washing
Remove the impurity such as water-soluble inorganic salt;It uses content to be recrystallized for 99% toluene centrifugation object, organic impurities is removed, is had
Body is:Centrifugation object is put into reaction kettle, 500kg toluene is added, is warming up to 86 DEG C, keeps the temperature 1.2 hours at this temperature, cooling
To 24 DEG C, is once centrifuged 8 minutes with the rotating speed of 3500rpm, and dried 3.2 hours under the conditions of 65 DEG C, it is chloro- to obtain 2,3- bis-
4- hydroxyanilines fine work.Wherein, the weight of 2,3-, bis- chloro- 4- hydroxyanilines fine work is 138~139kg, and content is
98.0%, yield 96%.
Step 4, by the n,N-Dimethylformamide (DMF) of 130kg 1- methyl cyclohexylpentanoic acid, 620kg dichloromethane and 2kg
Catalyst is added in chlorination tank, is warming up to 45 DEG C of back flow reactions, and 140kg thionyl chlorides, chlorination are added dropwise during back flow reaction
Sulfoxide was added at 2 hours, continued back flow reaction after being added dropwise to complete 6.5 hours, the sulfur dioxide and hydrogen chloride that back flow reaction generates
Gas is absorbed using 30% sodium hydroxide buck.After back flow reaction is fully completed, normal pressure recycles dichloromethane (can be with circulating sleeve
With), after dichloromethane has recycled, then excessive chlorine is recycled under conditions of temperature is 82.5 DEG C, negative pressure is -0.090MPa
Change sulfoxide, recycle 6.5 hours, 1- methyl ring formyl chloride is obtained after having recycled.Wherein, the weight of 1- methyl ring formyl chloride is
134kg, content 98%, yield 98%.
Step 5,2,3-, bis- chloro- 4- hydroxyanilines 120kg, 1- methyl rings formyl chloride is added into finished product kettle
113kg and ethyl acetate 820kg is warming up to 80 DEG C of back flow reactions, and triethylamine 74kg, triethylamine are added dropwise during back flow reaction
Continue back flow reaction 3 hours under the conditions of 80 DEG C after being dripped in 0.4 hour, is cooled to 24 DEG C after reaction ,-
It is filtered 8 minutes under the negative pressure of 0.09MPa, obtains triethylamine hydrochloride and mother liquor.10kg activated carbons are added into mother liquor, and (activated carbon is used
To decolourize and clean), it flows back 1.1 hours under the conditions of 80 DEG C, is filtered 8 minutes under the condition of negative pressure of -0.090MPa, is added
300kg water recycles ethyl acetate under the conditions of 78 DEG C of normal pressure, and recycling has recycled ethyl acetate in 2.5~3 hours, and it is outstanding to obtain finished product
It is floating to be centrifuged 8 minutes with the rotating speed of 3500rpm under the conditions of 40 DEG C in water, obtain crude product, dried 3.2 hours under the conditions of 75 DEG C,
Obtain fenhexamid.
Embodiment 3
A kind of synthetic method of fenhexamid, includes the following steps:
Step 1, aniline 90kg is added into reaction kettle, jacket refrigerating brine is opened, with 95 revs/min under the conditions of 40 DEG C
Rotating speed stirring, the hydrochloric acid 290kg being added dropwise in head tank is added while stirring, hydrochloric acid drips in 2 hours, and hydrochloric acid drips
After cool to 0 DEG C, under the conditions of 5 DEG C be added dropwise head tank in mass concentration be 60% sodium nitrite solution 122kg, sodium nitrite
Solution drips in 3 hours, after dripping at a temperature of 5 DEG C insulation reaction 2 hours, obtain diazol.
Step 2, the addition 120kg 2 into synthesis azo kettle, 3- chlorophenesic acids, 80kg sodium hydroxides and 900kg water, 2,
3- chlorophenesic acids, which are dissolved in sodium hydroxide solution, forms sodium phenolate, while water is as solution, with 95 revs/min of speed under room temperature
The primary stirring of degree 2 hours, allows 2,3- chlorophenesic acids to be dissolved completely in sodium hydroxide solution, is then cooled to -4 DEG C, 35
The diazol obtained by step 1 is dripped in minute, then under the conditions of 6 DEG C with 95 revs/min of speed secondary agitation 25 minutes,
It is centrifuged 8 minutes with the rotating speed of 3500rpm, removes sodium-chloride water solution, obtain azo compound.
Step 3, by the azo compound input reduction kettle obtained by step 2,95% ethyl alcohol 520kg and 50kg water, heating is added
To 45 DEG C, 13kg sodium hydroxides are first added and adjust pH value to 10, followed by be added 52kg sodium hydrosulfites (sodium dithionite,
Na2O4S2), 12.5kg sodium hydroxides and 50kg sodium hydrosulfites 7 times is added in repeated overlapping, and insulation reaction 4 is small at this temperature after adding
When, azo compound restores under the action of sodium hydrosulfite generates 2,3-, bis- chloro- 4- hydroxyanilines crude products and aniline.Then it is warming up to
62.5 DEG C and under -0.085MPa condition of negative pressure recycle ethyl alcohol, water and revert back come aniline, recycling 5 hours it is recyclable about
700kg mixtures.After having recycled, 800kg water is added into 2,3-, bis- chloro- 4- hydroxyanilines crude products, is warming up to 62.5 DEG C,
Heat preservation 1.5 hours, cools to 28 DEG C, is once centrifuged 12 minutes with the rotating speed of 3000rpm, obtains 180~200kg centrifugation objects, passes through
Washing removes the impurity such as water-soluble inorganic salt;It uses content to be recrystallized for 99% toluene centrifugation object, organic impurities is gone
It removes, specially:Centrifugation object is put into reaction kettle, 500kg toluene is added, is warming up to 85 DEG C, it is small to keep the temperature 1.5 at this temperature
When, 23 DEG C of crystallizations are cooled to, with the rotating speed secondary centrifuging 12 minutes of 3000rpm, and dries 2.8 hours, obtains under the conditions of 75 DEG C
Bis- chloro- 4- hydroxyanilines fine work of 2,3-.Wherein, the weight of 2,3-, bis- chloro- 4- hydroxyanilines fine work is 138~139kg,
Content is 98.0%, yield 96%.
Step 4, by the n,N-Dimethylformamide of 110kg 1- methyl cyclohexylpentanoic acid, 580kg dichloromethane and 0.5kg
(DMF) catalyst is added in chlorination tank, is warming up to 42.5 DEG C of back flow reactions, and 120kg protochlorides are added dropwise during back flow reaction
Sulfone, thionyl chloride are added with 2.5 hours, continue back flow reaction after being added dropwise to complete 7 hours, the sulfur dioxide that back flow reaction generates
It is absorbed using 30% sodium hydroxide buck with hydrogen chloride gas.After back flow reaction is fully completed, normal pressure recycles dichloromethane (can be with
Recycled), after dichloromethane has recycled, then recycling is excessive under conditions of temperature is 85 DEG C, negative pressure is -0.085MPa
Thionyl chloride, recycle 7 hours, 1- methyl ring formyl chloride obtained after recycle.Wherein, the weight of 1- methyl ring formyl chloride
For 134kg, content 98%, yield 98%.
Step 5,2,3-, bis- chloro- 4- hydroxyanilines 120kg, 1- methyl rings formyl chloride is added into finished product kettle
113kg and ethyl acetate 780kg is warming up to 79 DEG C of back flow reactions, and triethylamine 70kg, triethylamine are added dropwise during back flow reaction
Continue back flow reaction 2.5 hours under the conditions of 79 DEG C after being dripped in 1 hour, is cooled to 22 DEG C after reaction ,-
It is filtered 12 minutes under the negative pressure of 0.085MPa, obtains triethylamine hydrochloride and mother liquor.10kg activated carbon (activated carbons are added into mother liquor
For decolourizing and cleaning), the back flow reaction 1.2 hours under the conditions of 79 DEG C filters 12 points under the condition of negative pressure of -0.085MPa
300kg water is added in clock, and ethyl acetate is recycled under the conditions of 78 DEG C of normal pressure, and ethyl acetate has been recycled, obtained by recycling for 2.5~3 hours
Finished product suspends in water, is centrifuged 12 minutes with the rotating speed of 3000rpm under the conditions of 30 DEG C, obtains crude product, dried under the conditions of 85 DEG C
2.8 hours, obtain fenhexamid.
In above example, the content of aniline is 99.0%, and the content of hydrochloric acid is 31%, and the content of sodium nitrite is
99.0%, the content of 2,3- chlorophenesic acids is 99.0%, and the content of sodium hydroxide is 96.0%, and the content of sodium hydrosulfite is
85.0%, the content of ethyl alcohol is 95.0%, and the content of ethyl acetate is 99.0%, and the content of toluene is 99.0%, 1- methyl rings
Sour content is 99.0%, and the content of triethylamine is 99.0%, and the content of thionyl chloride is 99.0%.
For the content of the fenhexamid of gained of the invention 98% or more, yield reaches 86~87%, chloro- with 2,3- bis-
4- hydroxyanilines meters.In step 3, during azo compound reduction generates 2,3-, bis- chloro- 4- hydroxyanilines, also using sodium hydrosulfite
The reproducibility of original, sodium hydrosulfite is strong, fast in alkalescent reduction reaction speed, and the dosage for carrying out sodium hydrosulfite and sodium hydroxide carries out
Sodium hydroxide and sodium hydrosulfite are intersected input, conversion ratio can be made 98% or more by optimization, and adding sodium hydrosulfite has sour regurgitation existing
As between finally pH being made to maintain 6~7, without using hydrochloric acid tone pitch, reducing operating procedure.In step 4,1- methyl cyclohexylpentanoic acid chlorine
Change obtains 1- methyl ring in formyl chloride technique, and the dichloromethane of use is because of dichloro as solvent, rather than with toluene
The toxicity of methane is smaller than toluene, and safety is higher than toluene;And toluene boiling point is relatively high, in recycling, energy consumption is larger, and the time is long,
And the low boiling point of dichloromethane, it easily recycles and applies mechanically, low energy consumption, takes short.In step 5,2,3- bis- chloro- 4- hydroxyanilines
With during the 1- methyl ring fenhexamid of formyl chloride synthesis using ethyl acetate as solvent, not using toluene, be because
Smaller than toluene for the toxicity of ethyl acetate, safety is higher than toluene;And toluene boiling point is relatively high, in recycling, energy consumption is larger, when
Between long, and the low boiling point of ethyl acetate, easily recycle, low energy consumption, takes short.In step 5, the effect that triethylamine is added is to absorb instead
The HCl gases that should be generated in the process, make it be converted into triethylamine hydrochloride.
Although the present invention is described in detail with a general description of the specific embodiments in this specification,
But on the basis of the present invention, it can be made some modifications or improvements, this will be apparent to those skilled in the art.
Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, belong to claimed model
It encloses.
Claims (10)
1. a kind of fenhexamid, which is characterized in that including following raw material:Aniline, hydrochloric acid, sodium nitrite solution, 2,3- dichloro-benzenes
Phenol, sodium hydroxide, water, ethyl alcohol, sodium hydrosulfite, 1- methyl cyclohexylpentanoic acid, dichloromethane, n,N-Dimethylformamide, thionyl chloride,
Ethyl acetate and triethylamine.
2. fenhexamid according to claim 1, which is characterized in that the dosage of the raw material is:70-90 parts of aniline, salt
270-290 parts sour, 110-122 parts of sodium nitrite solution, 120-140 parts of 2,3- chlorophenesic acids, 164-171 parts of sodium hydroxide, water
950-1150 parts, 480-520 parts of ethyl alcohol, 336-364 parts of sodium hydrosulfite, 110-130 parts of 1- methyl cyclohexylpentanoic acids, dichloromethane 580-
620 parts, 1-2 parts of n,N-Dimethylformamide, 120-140 parts of thionyl chloride, 780-820 parts of ethyl acetate and triethylamine 70-74
Part.
3. a kind of synthetic method of fenhexamid, which is characterized in that include the following steps:
Step 1, hydrochloric acid is added dropwise while stirring into aniline, cools down, is added dropwise to sodium nitrite solution, insulation reaction obtains diazol;
Step 2,2,3- chlorophenesic acids, sodium hydroxide and water are mixed, primary to stir, the diazol is added dropwise in cooling, secondary
Stirring, centrifugation, obtains azo compound;
Step 3, second alcohol and water is added into the azo compound, heating intersects sodium hydroxide and sodium hydrosulfite are added in batches successively,
Insulation reaction, negative pressure recycle ethyl alcohol, water and aniline, obtain 2,3-, bis- chloro- 4- hydroxyanilines crude products;It is chloro- to the 2,3- bis-
4- hydroxyanilines crude products are washed, primary to centrifuge, and are obtained centrifugation object, are recrystallized to the centrifugation object, secondary centrifuging, are dried
It is dry, obtain 2,3-, bis- chloro- 4- hydroxyanilines;
Step 4,1- methyl cyclohexylpentanoic acid, dichloromethane and n,N-Dimethylformamide are mixed, back flow reaction, in back flow reaction
Thionyl chloride is added dropwise, continues back flow reaction, normal pressure recycles dichloromethane, and negative pressure recycles thionyl chloride, obtains 1- methyl ring formyl
Chlorine;
Step 5, by 2,3-, bis- chloro- 4- hydroxyanilines, 1- methyl ring, formyl chloride and ethyl acetate mix, back flow reaction,
Triethylamine is added dropwise during back flow reaction, continues back flow reaction, cools down, filters, obtains triethylamine hydrochloride and mother liquor;To the mother
Liquid is decolourized and is cleaned, and washing, normal pressure recycles ethyl acetate, is centrifuged, and drying obtains fenhexamid.
4. the synthetic method of fenhexamid according to claim 3, which is characterized in that in step 1, the temperature of the stirring
It it is 25~40 DEG C, the rotating speed of stirring is 95 revs/min;The time for adding of the hydrochloric acid is 1.5~2 hours;The cooling is drop
For temperature to 0~5 DEG C, the time for adding of sodium nitrite solution is 2.5~3 hours;The temperature of the insulation reaction is 0~5 DEG C, heat preservation
The time of reaction is 1~2 hour.
5. the synthetic method of fenhexamid according to claim 3, which is characterized in that in step 2, the sodium hydroxide with
The mass ratio of 2, the 3- chlorophenesic acids is 80:(120-140);The mass ratio of the water and 2, the 3- chlorophenesic acids is
(900-1100):(120-140).
6. the synthetic method of fenhexamid according to claim 3, which is characterized in that described once to stir in step 2
Rotating speed is 95 revs/min, and the time once stirred is 1~2 hour;The cooling is to be cooled to-(4~6) DEG C;The diazonium
The time for adding of salt is 25~35 minutes;The temperature of the secondary agitation is 4~6 DEG C, and the rotating speed of secondary agitation is 95 revs/min
The time of clock, secondary agitation is 25~35 minutes.
7. the synthetic method of fenhexamid according to claim 3, which is characterized in that in step 3, the heating is heating
To 40~45 DEG C;Each point of 7 addition of the sodium hydroxide and sodium hydrosulfite, the amount for the sodium hydroxide being added every time is identical, adds every time
The amount of the sodium hydrosulfite entered is identical;The temperature of the insulation reaction is 40~50 DEG C, and the time of insulation reaction is 4~5 hours.
8. the synthetic method of fenhexamid according to claim 3, which is characterized in that in step 3, the washing is by following
Step:Water is added into 2,3-, bis- chloro- 4- hydroxyanilines crude products, is warming up to 60~65 DEG C, keeps the temperature 1~1.5 hour, cooling
To 30 DEG C or less.
9. the synthetic method of fenhexamid according to claim 3, which is characterized in that in step 4, the back flow reaction
Temperature is 40~45 DEG C;The time for adding of the thionyl chloride is 1.5~2.5 hours;The time for continuing back flow reaction is 6
~7 hours.
10. the synthetic method of fenhexamid according to claim 3, which is characterized in that in step 5, the back flow reaction
Temperature be 78~80 DEG C;The time for adding of the triethylamine is 0.4~1 hour;The temperature for continuing back flow reaction is 78
~80 DEG C, the time for continuing back flow reaction is 2~3 hours;The cooling is to be cooled to 25 DEG C or less.
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| US5059623A (en) * | 1988-04-29 | 1991-10-22 | Bayer Aktiengesellschaft | Substituted cycloalkyl- and heterocyclyl-carboxanilides |
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| US5621141A (en) * | 1995-01-04 | 1997-04-15 | Bayer Aktiengesellschaft | Process for the preparation of alkylcarboxylic acid 4-hydroxyanilides |
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