CN106187894A - The preparation method of 1 methyl 3 ethyl 4 chlorine 5 pyrazole carboxylic acid ethyl ester - Google Patents
The preparation method of 1 methyl 3 ethyl 4 chlorine 5 pyrazole carboxylic acid ethyl ester Download PDFInfo
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- CN106187894A CN106187894A CN201610523994.4A CN201610523994A CN106187894A CN 106187894 A CN106187894 A CN 106187894A CN 201610523994 A CN201610523994 A CN 201610523994A CN 106187894 A CN106187894 A CN 106187894A
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- carboxylic acid
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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
- C07D231/16—Halogen atoms or nitro radicals
Abstract
The preparation method of a kind of 1 methyl 3 ethyl 4 chlorine 5 pyrazole carboxylic acid ethyl ester disclosed by the invention, comprises the following steps: a) 3 ethyl 5 pyrazole carboxylic acid ethyl esters and dimethyl carbonate being mixed, reaction generates 1 methyl 3 ethyl 5 pyrazole carboxylic acid ethyl ester；B) adding hydrochloric acid, hydrogen peroxide in the 1 methyl 3 ethyl 5 pyrazole carboxylic acid ethyl ester that step a) obtains, reaction generates 1 methyl 3 ethyl 4 chlorine 5 pyrazole carboxylic acid ethyl ester.The present invention is with dimethyl carbonate as green reagent, and it substitutes highly toxic material dimethyl sulfate and prepares 1 methyl 3 ethyl 5 pyrazole carboxylic acid ethyl ester；Use concentrated hydrochloric acid and hydrogen peroxide to substitute sulfonic acid chloride and carry out chlorination, prepare 1 methyl 3 ethyl 4 chlorine 5 pyrazole carboxylic acid ethyl ester；Improve the safety coefficient of production process, and poisonous sulfide and chloride will not be produced, reduce environmental protection pressure.
Description
Technical field
The present invention relates to the former medicine such as tebufenpyrad and Tolfenpyrad field, particularly relate to a kind of 1-methyl-3-ethyl-4-chloro-
The preparation method of 5-pyrazole carboxylic acid ethyl ester.
Background technology
Tebufenpyrad is Mitsubishi Co., Ltd. found in 1987 have the wide spectrum of pyrazoles carboxylic acid amides structure, safety,
Efficient novel acaricide, by Mitsubishi and American Cyanamid Company, mountain pass scholar company joint development, and with trade name Masai
Or pyranica listing, sell in multiple countries.Tolfenpyrad is that Mitsubishi chemical company is in the novel pyrrole of exploitation in 1988
Azoles heterocyclic Insecticidal and acaricidal agent.Tebufenpyrad and Tolfenpyrad both acaricides have high efficiency and safety, are widely used in anti-
Control the insect on the crops such as vegetable, fruit tree, flowers, Folium Camelliae sinensis, in plant, soil and water can quickly be degraded, be pesticide
The great development potentiality in boundary and the agricultural insecticida acaricide of the market vitality.1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid second
Ester is the key of the former medicine of above two, necessary intermediate, and the most conventional industrial preparative method is: first by 3-ethyl-5-pyrazoles
Ethyl formate and dimethyl sulfate react generation 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester, then by 1-methyl-3-ethyl-5-
Pyrazole carboxylic acid ethyl ester and sulfonic acid chloride react and prepare.But, dimethyl sulfate has high toxicity, and chemical property is active, course of reaction
The a large amount of by-product of middle generation；Sulfonic acid chloride is corrosives, meets water and releases toxic chlorinated hydrogen and sulfur dioxide gas, and generation of being heated is poisonous
Sulfide and chloride smog, add environmental protection pressure, also result in harm greatly to worker is healthy.
Summary of the invention
In view of this, the present invention provides the preparation method of a kind of 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester, should
Method uses the low toxicity raw material that is easy to get to replace high toxogen material, and will not produce toxicity sulfide and chloride gas, decrease tail
Gas disposal input and environmental protection pressure.
The technical scheme is that and be achieved in that:
The preparation method of a kind of 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester, comprises the following steps:
A) 3-ethyl-5-pyrazole carboxylic acid ethyl ester and dimethyl carbonate being mixed, reaction generates 1-methyl-3-ethyl-5-pyrrole
Iminazole acid ethyl ester；
B) adding hydrochloric acid, hydrogen peroxide in the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester that step a) obtains, reaction is raw
Become 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
Preferably, the autoclave of nitrogen atmosphere adds 3-ethyl-5-pyrazole carboxylic acid ethyl ester, dimethyl carbonate, in temperature
Degree is to react 8～12h at 100～150 DEG C, obtains 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Preferably, described 3-ethyl-5-pyrazole carboxylic acid ethyl ester and described dimethyl carbonate, pressure be 0.5～1.1MPa,
React under the effect of potassium carbonate；Described 3-ethyl-5-pyrazole carboxylic acid ethyl ester, described dimethyl carbonate, described potassium carbonate mole
Ratio is 1:(5～7): (1～1.5).
Preferably, described 3-ethyl-5-pyrazole carboxylic acid ethyl ester and described dimethyl carbonate, at polar solvent diethylene glycol dimethyl
Ether, normal pressure, potassium carbonate effect under react；Described 3-ethyl-5-pyrazole carboxylic acid ethyl ester, described dimethyl carbonate, described carbonic acid
Potassium, the mol ratio of described diethylene glycol dimethyl ether are 1:(1～1.2): (1～1.5): (4～5).
Preferably, also include the first subtractive process, the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester obtained by step a)
Temperature be reduced to 15～25 DEG C, filter out salt, deviate from dimethyl carbonate, vacuum distillation, obtain refined 1-methyl-3-ethyl-
5-pyrazole carboxylic acid ethyl ester.
Preferably, in the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester that step a) obtains, hydrochloric acid and two chloroethenes are added
Alkane, control temperature, at 20～30 DEG C, is slowly added dropwise hydrogen peroxide；After completion of dropwise addition, it is incubated 1～2h, is warmed up to 50～70 DEG C, insulation
5～7h, obtain 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester；The mass concentration of described hydrochloric acid is 35～40%, described
The mass concentration of hydrogen peroxide is 30～40%；Described 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester, described dichloroethanes, described
Hydrochloric acid, the mol ratio of described hydrogen peroxide are 1:(11～14): (1～1.5): (1.1～1.6).
Preferably, also include the second subtractive process, the 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid obtained by step b)
The temperature of ethyl ester is reduced to 20～30 DEG C, stands, layering；It is 4 by mass concentration the most respectively～the sodium sulfite of 6%, quality are dense
Degree is 4～the sodium carbonate of 6% and water wash；Finally it is dried with anhydrous sodium sulfate, sloughs dichloroethanes, obtain refined 1-first
Base-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
By technique scheme it can be seen that the present invention provide 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester
Preparation method, with dimethyl carbonate as green reagent, its substitute highly toxic material dimethyl sulfate prepare 1-methyl-3-second
Base-5-pyrazole carboxylic acid ethyl ester；Use concentrated hydrochloric acid and hydrogen peroxide to substitute sulfonic acid chloride and carry out chlorination, prepare 1-methyl-3-ethyl-4-
Chloro-5-pyrazole carboxylic acid ethyl ester；Improve the safety coefficient of production process, and poisonous sulfide and chloride will not be produced, reduce
Environmental protection pressure.
Detailed description of the invention
The invention discloses the preparation method of 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester, people in the art
Member 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.The method of the present invention and quoting
Being described by preferred embodiment, related personnel substantially can be right in without departing from present invention, spirit and scope
Method described herein and application are modified or suitably change and combine, and realize and apply the technology of the present invention.
The preparation method of a kind of 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester, comprises the following steps:
A) 3-ethyl-5-pyrazole carboxylic acid ethyl ester and dimethyl carbonate being mixed, reaction generates 1-methyl-3-ethyl-5-pyrrole
Iminazole acid ethyl ester；
B) adding hydrochloric acid, hydrogen peroxide in the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester that step a) obtains, reaction is raw
Become 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
In the present invention, dimethyl carbonate is green reagent, its substitute highly toxic material dimethyl sulfate prepare 1-methyl-
3-ethyl-5-pyrazole carboxylic acid ethyl ester；Use hydrochloric acid and hydrogen peroxide to substitute sulfonic acid chloride and carry out chlorination, prepare 1-methyl-3-ethyl-4-
Chloro-5-pyrazole carboxylic acid ethyl ester；Improve the safety coefficient of production process, and poisonous sulfide and chloride will not be produced, reduce
Environmental protection pressure.
In the present invention, 3-ethyl-5-pyrazole carboxylic acid ethyl ester and dimethyl carbonate mixing, reaction generates 1-methyl-3-second
Base-5-pyrazole carboxylic acid ethyl ester.In an embodiment of the present invention, 3-ethyl-5-pyrazole carboxylic acid ethyl ester and dimethyl carbonate are at nitrogen
In the autoclave of atmosphere, react 8～12h at 100～150 DEG C, obtain 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester；Additionally
In embodiment, 3-ethyl-5-pyrazole carboxylic acid ethyl ester and dimethyl carbonate, pressure be 0.8～0.9MPa, under the effect of potassium carbonate
Reaction；3-ethyl-5-pyrazole carboxylic acid ethyl ester, dimethyl carbonate, the mol ratio of potassium carbonate are 1:(5～7): (1～1.5)；At it
In his embodiment, 3-ethyl-5-pyrazole carboxylic acid ethyl ester and dimethyl carbonate, at polar solvent diethylene glycol dimethyl ether, normal pressure, carbonic acid
React under the effect of potassium；3-ethyl-5-pyrazole carboxylic acid ethyl ester, dimethyl carbonate, potassium carbonate, the mol ratio of diethylene glycol dimethyl ether are
1:(1～1.2): (1～1.5): (4～5).
It should be noted that the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester for preparing of said method also has other
Impurity, need to refine；Subtractive process is, the temperature of the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester obtained is reduced to 15
～25 DEG C, filter out salt, deviate from dimethyl carbonate, vacuum distillation.
Use the purity of 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester that said method prepares more than 95.3%,
Yield is more than 82.53%.
In the present invention, adding hydrochloric acid, hydrogen peroxide in 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester, reaction generates 1-
Methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.In an embodiment of the present invention, 1-methyl-3-ethyl-5-pyrazole carboxylic acid second
Adding hydrochloric acid and dichloroethanes in ester, control temperature, at 20～30 DEG C, is slowly added dropwise hydrogen peroxide；After completion of dropwise addition, insulation 1～
2h, is warmed up to 50～70 DEG C, is incubated 5～7h, obtains 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester；The quality of hydrochloric acid
Concentration is 35～40%, and the mass concentration of hydrogen peroxide is 30～40%；1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester, two chloroethenes
Alkane, hydrochloric acid, the mol ratio of hydrogen peroxide are 1:(11～14): (1～1.5): (1.1～1.6).
It should be noted that the 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester that said method prepares is same
Need refined；Subtractive process is, the temperature of 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester is reduced to 20～30 DEG C, quiet
Put, layering；It is 4 by mass concentration the most respectively～the sodium sulfite of 6%, mass concentration are 4～the sodium carbonate of 6% and water are washed
Wash；Finally it is dried with anhydrous sodium sulfate, sloughs dichloroethanes.
1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid the ethyl ester that the technical scheme using the present invention to provide prepares
Purity is up to 96.9%, and yield is up to 95.2%.
In order to further illustrate the present invention, a kind of 1-methyl-3-ethyl-4-present invention provided below in conjunction with embodiment
The preparation method of chloro-5-pyrazole carboxylic acid ethyl ester is described in detail.
Raw material used in following example is commercially available.
Embodiment 1
To with nitrogen replace after autoclave in put into 168g 3-ethyl-5-pyrazole carboxylic acid ethyl ester, 179.4g potassium carbonate and
540g dimethyl carbonate, is warmed up to 120 DEG C, pressure to 0.83MPa, is incubated 10 hours.Cool to 22 DEG C, filter out salt, abjection
Dimethyl carbonate, negative pressure letter is steamed, is obtained 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Embodiment 2
To with nitrogen replace after autoclave in put into 168g 3-ethyl-5-pyrazole carboxylic acid ethyl ester, 207g potassium carbonate and
630g dimethyl carbonate, is warmed up to 150 DEG C, pressure to 1.1MPa, is incubated 8 hours.Cool to 18 DEG C, filter out salt, deviate from carbon
Dimethyl phthalate, negative pressure letter is steamed, is obtained 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Embodiment 3
To with nitrogen replace after autoclave in put into 168g 3-ethyl-5-pyrazole carboxylic acid ethyl ester, 138g potassium carbonate and
450g dimethyl carbonate, is warmed up to 100 DEG C, pressure to 0.93MPa, is incubated 8 hours.Cool to 25 DEG C, filter out salt, deviate from carbon
Dimethyl phthalate, negative pressure letter is steamed, is obtained 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Embodiment 4
To with nitrogen replace after autoclave in put into 168g 3-ethyl-5-pyrazole carboxylic acid ethyl ester, 165.6g potassium carbonate and
585g dimethyl carbonate, is warmed up to 120 DEG C, pressure to 0.5MPa, is incubated 12 hours.Cool to 20 DEG C, filter out salt, deviate from carbon
Dimethyl phthalate, negative pressure letter is steamed, is obtained 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Embodiment 5
Input 168g 3-ethyl-5-pyrazole carboxylic acid ethyl ester in reactor after replacing with nitrogen, 179.4g potassium carbonate,
600mL diethylene glycol dimethyl ether and 99g dimethyl carbonate, be warmed up to 120 DEG C, normal pressure, is incubated 10 hours.Cool to 15 DEG C, filter
Going out salt, deviate from solvent, negative pressure letter is steamed, and obtains 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Embodiment 6
Input 168g 3-ethyl-5-pyrazole carboxylic acid ethyl ester in reactor after replacing with nitrogen, 207g potassium carbonate,
700mL diethylene glycol dimethyl ether and 90g dimethyl carbonate, be warmed up to 80 DEG C, normal pressure, is incubated 12 hours.Cool to 20 DEG C, filter out
Salt, deviates from solvent, and negative pressure letter is steamed, and obtains 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Embodiment 7
Input 168g 3-ethyl-5-pyrazole carboxylic acid ethyl ester in reactor after replacing with nitrogen, 165.6g potassium carbonate,
650mL diethylene glycol dimethyl ether and 108g dimethyl carbonate, be warmed up to 100 DEG C, normal pressure, is incubated 8 hours.Cool to 20 DEG C, filter
Going out salt, deviate from solvent, negative pressure letter is steamed, and obtains 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Embodiment 8
Input 168g 3-ethyl-5-pyrazole carboxylic acid ethyl ester in reactor after replacing with nitrogen, 138g potassium carbonate,
750mL diethylene glycol dimethyl ether and 103.5g dimethyl carbonate, be warmed up to 120 DEG C, normal pressure, is incubated 10 hours.Cool to 25 DEG C, mistake
Leaching salt, deviate from solvent, negative pressure letter is steamed, and obtains 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
Embodiment 9
In four-hole bottle add 23.8g embodiment 1 prepare 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester,
13.1mL mass concentration is hydrochloric acid and the 125mL dichloroethanes of 37%, and control temperature, at 25 DEG C, is slowly added dropwise 14.2mL mass dense
Degree is the hydrogen peroxide of 35%；After completion of dropwise addition, it is incubated 1.5h, is warmed up to 60 DEG C, be incubated 6h；Reduce the temperature to 30 DEG C again, stand,
Layering；Wash with 5% sodium sulfite, 5% sodium carbonate and water the most respectively；Finally it is dried with anhydrous sodium sulfate, sloughs dichloro
Ethane obtains 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
Embodiment 10
In four-hole bottle add 23.8g embodiment 1 prepare 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester,
10.25mL mass concentration is hydrochloric acid and the 106mL dichloroethanes of 35%, and control temperature, at 20 DEG C, is slowly added dropwise 11.6mL mass
Concentration is the hydrogen peroxide of 37%；After completion of dropwise addition, it is incubated 2h, is warmed up to 50 DEG C, be incubated 7h；Reduce the temperature to 30 DEG C again, stand,
Layering；Wash with 4% sodium sulfite, 4% sodium carbonate and water the most respectively；Finally it is dried with anhydrous sodium sulfate, sloughs dichloro
Ethane obtains 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
Embodiment 11
In four-hole bottle add 23.8g embodiment 1 prepare 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester,
15.2mL mass concentration is hydrochloric acid and the 135mL dichloroethanes of 37%, and control temperature, at 30 DEG C, is slowly added dropwise 17.1mL mass dense
Degree is the hydrogen peroxide of 30%；After completion of dropwise addition, it is incubated 2h, is warmed up to 70 DEG C, be incubated 5h；Reduce the temperature to 20 DEG C again, stand, point
Layer；Wash with 6% sodium sulfite, 6% sodium carbonate and water the most respectively；Finally it is dried with anhydrous sodium sulfate, sloughs two chloroethenes
Alkane obtains 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
Embodiment 12
In four-hole bottle add 23.8g embodiment 1 prepare 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester,
14.1mL mass concentration is hydrochloric acid and the 127mL dichloroethanes of 38%, and control temperature, at 26 DEG C, is slowly added dropwise 11.5mL mass dense
Degree is the hydrogen peroxide of 40%；After completion of dropwise addition, it is incubated 1.8h, is warmed up to 55 DEG C, be incubated 5.5h；Reduce the temperature to 24 DEG C again, quiet
Put, layering；Wash with 5.5% sodium sulfite, 5.5% sodium carbonate and water the most respectively；Finally it is dried with anhydrous sodium sulfate, de-
Dichloroethanes is gone to obtain 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
Embodiment 13
In four-hole bottle add 23.8g embodiment 1 prepare 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester,
10.18mL mass concentration is hydrochloric acid and the 130mL dichloroethanes of 40%, and control temperature, at 22 DEG C, is slowly added dropwise 14.2mL mass
Concentration is the hydrogen peroxide of 35%；After completion of dropwise addition, it is incubated 1.2h, is warmed up to 65 DEG C, be incubated 5.5h；Reduce the temperature to 20 DEG C again,
Stand, layering；Wash with 4.5% sodium sulfite, 5% sodium carbonate and water the most respectively；Finally it is dried with anhydrous sodium sulfate, de-
Dichloroethanes is gone to obtain 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
1-methyl-3-ethyl-5-pyrazole carboxylic acid the ethyl ester that embodiment 1～8 is prepared, and embodiment 9～13 preparation
1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid the ethyl ester obtained carries out the test of purity and yield, result such as table 1, table 2 institute
Show:
The yield of the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester that table 1 embodiment 1～8 prepares and purity
| Yield (%) | Purity (%) | |
| Embodiment 1 | 88.47 | 95.3 |
| Embodiment 2 | 87.77 | 94.8 |
| Embodiment 3 | 80.30 | 94.0 |
| Embodiment 4 | 72.39 | 92.8 |
| Embodiment 5 | 82.53 | 96.1 |
| Embodiment 6 | 76.07 | 95.7 |
| Embodiment 7 | 81.22 | 95.4 |
| Embodiment 8 | 78.73 | 91.7 |
The yield of the 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester that table 2 embodiment 9～13 prepares and purity
| Yield (%) | Purity (%) | |
| Embodiment 9 | 95.2 | 96.9% |
| Embodiment 10 | 77.2 | 92.7% |
| Embodiment 11 | 94.5 | 95.2% |
| Embodiment 12 | 91.7 | 92.3% |
| Embodiment 13 | 88.6 | 90.4% |
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 (7)
1. the preparation method of a 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester, it is characterised in that include following step
Rapid:
A) 3-ethyl-5-pyrazole carboxylic acid ethyl ester and dimethyl carbonate being mixed, reaction generates 1-methyl-3-ethyl-5-pyrazoles first
Acetoacetic ester；
B) adding hydrochloric acid, hydrogen peroxide in the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester that step a) obtains, reaction generates 1-
Methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
2. preparation method as claimed in claim 1, it is characterised in that add 3-ethyl-5-in the autoclave of nitrogen atmosphere
Pyrazole carboxylic acid ethyl ester, dimethyl carbonate, react 8～12h at temperature is 100～150 DEG C, obtain 1-methyl-3-ethyl-5-pyrrole
Iminazole acid ethyl ester.
3. preparation method as claimed in claim 2, it is characterised in that described 3-ethyl-5-pyrazole carboxylic acid ethyl ester and described carbon
Dimethyl phthalate, is 0.5～1.1MPa at pressure, reacts under the effect of potassium carbonate；Described 3-ethyl-5-pyrazole carboxylic acid ethyl ester, institute
State dimethyl carbonate, the mol ratio of described potassium carbonate is 1:(5～7): (1～1.5).
4. preparation method as claimed in claim 2, it is characterised in that described 3-ethyl-5-pyrazole carboxylic acid ethyl ester and described carbon
Dimethyl phthalate, polar solvent diethylene glycol dimethyl ether, normal pressure, potassium carbonate effect under react；Described 3-ethyl-5-pyrazole carboxylic acid
Ethyl ester, described dimethyl carbonate, described potassium carbonate, the mol ratio of described diethylene glycol dimethyl ether are 1:(1～1.2): (1～1.5):
(4～5).
5. the preparation method as described in any one of Claims 1 to 4, it is characterised in that also include the first subtractive process, by step
The temperature of the 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester a) obtained is reduced to 15～25 DEG C, filters out salt, deviates from carbonic acid two
Methyl ester, vacuum distillation, obtain refined 1-methyl-3-ethyl-5-pyrazole carboxylic acid ethyl ester.
6. the preparation method as described in any one of Claims 1 to 4, it is characterised in that the 1-methyl-3-second obtained to step a)
Adding hydrochloric acid and dichloroethanes in base-5-pyrazole carboxylic acid ethyl ester, control temperature, at 20～30 DEG C, is slowly added dropwise hydrogen peroxide；Dropping
After end, it is incubated 1～2h, is warmed up to 50～70 DEG C, be incubated 5～7h, obtain 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid second
Ester；The mass concentration of described hydrochloric acid is 35～40%, and the mass concentration of described hydrogen peroxide is 30～40%；Described 1-methyl-3-
Ethyl-5-pyrazole carboxylic acid ethyl ester, described dichloroethanes, described hydrochloric acid, the mol ratio of described hydrogen peroxide are 1:(11～14): (1～
1.5): (1.1～1.6).
7. preparation method as claimed in claim 6, it is characterised in that also include the second subtractive process, step b) is obtained
The temperature of 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester is reduced to 20～30 DEG C, stands, layering；Use quality the most respectively
Concentration is 4～the sodium sulfite of 6%, mass concentration are 4～the sodium carbonate of 6% and water wash；Finally use anhydrous sodium sulfate
It is dried, sloughs dichloroethanes, obtain refined 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid ethyl ester.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114561435A (en) * | 2022-04-27 | 2022-05-31 | 南京科力硕生物科技有限公司 | Method for preparing 4-chloro-3-ethyl-1-methylpyrazole-5-formic acid by using magnetic carbon nanotube immobilized enzyme catalysis |
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