CN106831586A - A kind of pyrazole amine preparation method - Google Patents
A kind of pyrazole amine preparation method Download PDFInfo
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- CN106831586A CN106831586A CN201710006650.0A CN201710006650A CN106831586A CN 106831586 A CN106831586 A CN 106831586A CN 201710006650 A CN201710006650 A CN 201710006650A CN 106831586 A CN106831586 A CN 106831586A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
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Abstract
The invention discloses a kind of pyrazole amine preparation method of chemical technology field, the pyrazole amine preparation method is comprised the following steps that：S1：Vacuum is pumped into 800~1000kg of toluene in 2000L cyclization kettles；S2：Salt solution is passed through in kettle chuck and less than 5 DEG C are cooled to；S3：After completion of dropping, 25~30 DEG C of reaction 1h are to slowly warm up to；S4：Add 320~360kg of water and be cooled to 10 DEG C；S5：Blowing suction filtration under agitation, the present invention carries out temperature section control in same reactor, without catalyst, reaction is not evaporated off solvent after terminating, directly lower the temperature freezing and crystallizing, the present invention before the decrease temperature crystalline to system in add a certain amount of water, to reduce solubility of the system to product, precipitation is preferably crystallized with sharp product.Product is dried after filtering, centrifugation, toluenic mother liquor can Reusability without influence product yield and quality, and site environment is effectively improved, and shortens the production time, greatly reduces workman's productive labor intensity.
Description
Technical field
The present invention relates to chemical technology field, specially a kind of pyrazole amine preparation method.
Background technology
Pyrazole amine, Chinese nickname：5- amino -1- methylpyrazole -4- Ethyl formates；5- amino -1- methyl -4- carbethoxyl groups
Pyrazoles, No. CAS：31037-02-2.Molecular formula：C7H11N3O2.Molecular weight：169.1811.Pesticide intermediate is mainly used as, can
It is used directly to synthesize sulfonamide.Pyrazole amine is the precursor for synthesizing the phonetic sulfonamide of pyrrole, and the latter is the important centre for synthesizing pyrazosulfuron
Body.It is at present mostly, with toluene as solvent, to be carried out in the presence of catalyst with methyl hydrazine by methene that the synthesis of pyrazole amine is domestic
Ring-closure reaction, reaction end steams toluene, while hot blowing crystallisation by cooling, obtains big bulk crude product, then through broken, centrifugation, it is cold
Dry and obtain after water rinsing.Weight yield 85% or so.
Due to being blowing while hot, site environment is severe, and the bulk materials obtained after cooling need hand breaking, labour intensity
Greatly, per batch, reaction terminates that solvent will be evaporated off, and energy consumption is big, therefore, we have proposed a kind of pyrazole amine preparation method input
Use, to solve the above problems.
The content of the invention
It is an object of the invention to provide a kind of pyrazole amine preparation method, with solve to propose in above-mentioned background technology due to
It is blowing while hot, site environment is severe, the bulk materials obtained after cooling need hand breaking, labour intensity is big, the reaction per batch
Solvent will be evaporated off for end, the big problem of energy consumption.
To achieve the above object, the present invention provides following technical scheme：It is prepared by a kind of pyrazole amine preparation method, the pyrazole amine
Method is comprised the following steps that：
S1：Vacuum is pumped into 800~1000kg of toluene in 2000L cyclization kettles, and puts into 400~500kg of methene, in 20~
30 DEG C of 25~35min of stirring；
S2：After material it is molten it is clear after, salt solution is passed through in kettle chuck and less than 5 DEG C are cooled to, dropwise addition methyl hydrazine 320~
350kg, and temperature control is below 15 DEG C；
S3：After completion of dropping, 25~30 DEG C of reaction 1h are to slowly warm up to, then are warming up to 35~40 DEG C of reaction 1h, risen again
Temperature is finally warming up to 55~60 DEG C and is incubated to 45~50 DEG C of reaction 1h；
S4：After the completion of reaction, 320~360kg of water is added simultaneously to be cooled to -10 DEG C, stand 25 after maintaining crystallization 2 hours~
35min；
S5：Blowing suction filtration under agitation, filter cake discharges into the drying more than 8 hours of 40~50 DEG C of drying room, prepares pyrazole amine.
Preferably, in the step S2, air blast cooling is carried out using air-cooler, wherein the rotating speed of air-cooler be 2000~
2500r/min。
Preferably, in the step S3, the whole reaction time continues 6h, and reaction time timing is completed from methyl hydrazine is added dropwise
After start.
Preferably, in the step S5, filtrate goes layering kettle to separate lower floor's water phase, and organic phase returns to cyclization kettle and repeats to make
With.
Compared with prior art, the beneficial effects of the invention are as follows：The present invention carries out temperature section control in same reactor
System, without catalyst, reaction is not evaporated off solvent after terminating, freezing and crystallizing of directly lowering the temperature.To obtain yield higher, the present invention exists
To a certain amount of water is added in system before decrease temperature crystalline, to reduce solubility of the system to product, preferably crystallized with sharp product
Separate out.Product is dried after filtering, centrifugation, toluenic mother liquor can Reusability without influence product yield and quality, and live ring
Border is effectively improved, and shortens the production time, greatly reduces workman's productive labor intensity.
Brief description of the drawings
Fig. 1 is workflow diagram of the present invention.
Specific embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete
Site preparation is described, it is clear that described embodiment is only a part of embodiment of the invention, rather than whole embodiments.It is based on
Embodiment in the present invention, it is every other that those of ordinary skill in the art are obtained under the premise of creative work is not made
Embodiment, belongs to the scope of protection of the invention.
Embodiment one
A kind of pyrazole amine preparation method, the pyrazole amine preparation method is comprised the following steps that：
S1：Vacuum is pumped into toluene 800kg in 2000L cyclization kettles, and puts into methene 450kg, and 25min is stirred in 20 DEG C；
S2：After material it is molten it is clear after, salt solution is passed through in kettle chuck and less than 5 DEG C are cooled to, dropwise addition methyl hydrazine 320kg, and
Temperature control carries out air blast cooling below 15 DEG C using air-cooler, and the wherein rotating speed of air-cooler is 2000r/min；
S3：After completion of dropping, 25 DEG C of reaction 1h are to slowly warm up to, then are warming up to 35 DEG C of reaction 1h, 45 DEG C are warming up to again
Reaction 1h, be finally warming up to 55 DEG C and be incubated, the whole reaction time continue 6h, and reaction time timing from be added dropwise methyl hydrazine
After the completion of start；
S4：After the completion of reaction, add water 320kg and be cooled to -10 DEG C, 25min is stood after maintaining crystallization 2 hours；
S5：Blowing suction filtration under agitation, filter cake discharges into the drying more than 8 hours of 40 DEG C of drying room, prepares pyrazole amine, filtrate
Layering kettle is gone to separate lower floor's water phase, organic phase returns to cyclization kettle and reuses.The pyrazole amine 395kg that the present embodiment is prepared, weight
Amount yield is 87.78%.
Embodiment two
A kind of pyrazole amine preparation method, the pyrazole amine preparation method is comprised the following steps that：
S1：Vacuum is pumped into toluene 900kg in 2000L cyclization kettles, and puts into methene 450kg, and 35min is stirred in 30 DEG C；
S2：After material it is molten it is clear after, salt solution is passed through in kettle chuck and less than 5 DEG C are cooled to, dropwise addition methyl hydrazine 350kg, and
Temperature control carries out air blast cooling below 15 DEG C using air-cooler, and the wherein rotating speed of air-cooler is 2500r/min；
S3：After completion of dropping, 30 DEG C of reaction 1h are to slowly warm up to, then are warming up to 40 DEG C of reaction 1h, 50 DEG C are warming up to again
Reaction 1h, be finally warming up to 60 DEG C and be incubated, the whole reaction time continue 6h, and reaction time timing from be added dropwise methyl hydrazine
After the completion of start；
S4：After the completion of reaction, add water 360kg and be cooled to -10 DEG C, 35min is stood after maintaining crystallization 2 hours；
S5：Blowing suction filtration under agitation, filter cake discharges into the drying more than 8 hours of 50 DEG C of drying room, prepares pyrazole amine, filtrate
Layering kettle is gone to separate lower floor's water phase, organic phase returns to cyclization kettle and reuses.The pyrazole amine 408kg that the present embodiment is prepared, weight
Amount yield is 90.67%.
Embodiment three
A kind of pyrazole amine preparation method, the pyrazole amine preparation method is comprised the following steps that：
S1：Vacuum is pumped into toluene 1000kg in 2000L cyclization kettles, and puts into methene 450kg, and 30min is stirred in 25 DEG C；
S2：After material it is molten it is clear after, salt solution is passed through in kettle chuck and less than 5 DEG C are cooled to, dropwise addition methyl hydrazine 340kg, and
Temperature control carries out air blast cooling below 15 DEG C using air-cooler, and the wherein rotating speed of air-cooler is 2300r/min；
S3：After completion of dropping, 27 DEG C of reaction 1h are to slowly warm up to, then are warming up to 38 DEG C of reaction 1h, 47 DEG C are warming up to again
Reaction 1h, be finally warming up to 58 DEG C and be incubated, the whole reaction time continue 6h, and reaction time timing from be added dropwise methyl hydrazine
After the completion of start；
S4：After the completion of reaction, 320~360kg of water is added simultaneously to be cooled to -10 DEG C, stand 25 after maintaining crystallization 2 hours~
35min；
S5：Blowing suction filtration under agitation, filter cake discharges into the drying more than 8 hours of 45 DEG C of drying room, prepares pyrazole amine, filtrate
Layering kettle is gone to separate lower floor's water phase, organic phase returns to cyclization kettle and reuses.The pyrazole amine 415kg that the present embodiment is prepared, weight
Amount yield is 92.2%.
In summary described, highly preferred embodiment of the present invention is embodiment three.
Although an embodiment of the present invention has been shown and described, for the ordinary skill in the art, can be with
Understanding can carry out various changes, modification, replacement to these embodiments without departing from the principles and spirit of the present invention
And modification, the scope of the present invention be defined by the appended.
Claims (4)
1. a kind of pyrazole amine preparation method, it is characterised in that：The pyrazole amine preparation method is comprised the following steps that：
S1：Vacuum is pumped into 800~1000kg of toluene in 2000L cyclization kettles, and puts into 400~500kg of methene, in 20~30 DEG C
25~35min of stirring；
S2：After material it is molten it is clear after, salt solution is passed through in kettle chuck and less than 5 DEG C are cooled to, dropwise addition 320~350kg of methyl hydrazine, and
Temperature control is below 15 DEG C；
S3：After completion of dropping, 25~30 DEG C of reaction 1h are to slowly warm up to, then are warming up to 35~40 DEG C of reaction 1h, be warming up to again
45~50 DEG C of reaction 1h, are finally warming up to 55~60 DEG C and are incubated；
S4：After the completion of reaction, add 320~360kg of water and be cooled to -10 DEG C, 25~35min of standing after maintaining to crystallize 2 hours；
S5：Blowing suction filtration under agitation, filter cake discharges into the drying more than 8 hours of 40~50 DEG C of drying room, prepares pyrazole amine.
2. a kind of pyrazole amine preparation method according to claim 1, it is characterised in that：In the step S2, using cold wind
Machine carries out air blast cooling, and the wherein rotating speed of air-cooler is 2000~2500r/min.
3. a kind of pyrazole amine preparation method according to claim 1, it is characterised in that：In the step S3, whole reaction
Time continues 6h, and since reaction time timing being added dropwise after the completion of methyl hydrazine.
4. a kind of pyrazole amine preparation method according to claim 1, it is characterised in that：In the step S5, filtrate is gone point
Layer kettle separates lower floor's water phase, and organic phase returns to cyclization kettle and reuses.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0810217A1 (en) * | 1996-05-29 | 1997-12-03 | Japan Energy Corporation | Pyrazole derivatives and their pharmaceutical use as smooth muscle cell growth inhibitors |
| CN102336709A (en) * | 2010-07-20 | 2012-02-01 | 龙口市福尔生化科技有限公司 | Method for synthesizing 1-methyl-4-ethyl formate-5-sulfonyl chloride-based pyrazole |
| CN102603638A (en) * | 2012-02-17 | 2012-07-25 | 张学生 | Synthesis process of pyrazole amine |
| CN105646357A (en) * | 2014-11-13 | 2016-06-08 | 吕艳 | 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester synthesis process |
-
2017
- 2017-01-05 CN CN201710006650.0A patent/CN106831586A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0810217A1 (en) * | 1996-05-29 | 1997-12-03 | Japan Energy Corporation | Pyrazole derivatives and their pharmaceutical use as smooth muscle cell growth inhibitors |
| CN102336709A (en) * | 2010-07-20 | 2012-02-01 | 龙口市福尔生化科技有限公司 | Method for synthesizing 1-methyl-4-ethyl formate-5-sulfonyl chloride-based pyrazole |
| CN102603638A (en) * | 2012-02-17 | 2012-07-25 | 张学生 | Synthesis process of pyrazole amine |
| CN105646357A (en) * | 2014-11-13 | 2016-06-08 | 吕艳 | 5-amino-1-methyl-1H-pyrazole-4-carboxylic acid ethyl ester synthesis process |
Non-Patent Citations (2)
| Title |
|---|
| GARY R. W. PITT，等: "Non-peptide oxytocin agonists", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| 李鹏，等: "除草剂吡嘧磺隆的研制", 《精细与专用化学品》 * |
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