CN104693164B - A kind of preparation method of 2,2 difluoro methyl piperates - Google Patents
A kind of preparation method of 2,2 difluoro methyl piperates Download PDFInfo
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- CN104693164B CN104693164B CN201510149045.XA CN201510149045A CN104693164B CN 104693164 B CN104693164 B CN 104693164B CN 201510149045 A CN201510149045 A CN 201510149045A CN 104693164 B CN104693164 B CN 104693164B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
- C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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Abstract
The present invention relates to organic synthesis field, more particularly to a kind of preparation method of 2,2 difluoro methyl piperates.The present invention provides a kind of preparation method of 2,2 difluoro methyl piperates, comprises the steps：By 2,2 difluoro pepper acyl fluorides（II）Act on methyl alcohol, 2,2 difluoro methyl piperates are prepared by esterification（III）, its reaction equation is as follows：Main advantages of the present invention are as follows：The synthetic route of the preparation method of provided by the present invention 2,2 difluoro methyl piperates is short, and technological process is easily controllable, completely, high income, the target product purity for preparing are high for reaction, steady quality, comply fully with the use requirement as agricultural chemicals or medicine intermediate, additionally, the raw material used by this method and reagent cheap, in each step reaction, solvent for use amount is few, produce waste liquid few, not only reduces cost reduces environmental pollution, is also highly convenient for large-scale commercial production.
Description
Technical field
The present invention relates to organic synthesis field, the more particularly to preparation method of one kind 2,2- difluoro methyl piperate.
Background technology
2,2- difluoro methyl piperates are a kind of increasingly extensive intermediates of purposes, be conventional synthesis pharmaceutical compound,
Agricultural chemical compound and the intermediate of electronic chemical product.In prior art be with the bromo- 2,2- difluoro piperonyl cyclonene of 5- and an oxidation
Carbon carries out reaction under high pressure under four triphenyl phosphorus palladium chtalyst, prepares corresponding 2,2- difluoro methyl piperate
(WO2005075435).The method is relatively costly, and the raw material used by which need to be obtained through superchlorination, fluorination, bromination, and step is long,
Overall reaction yield is relatively low.
Content of the invention
The shortcoming of prior art in view of the above, it is an object of the invention to provide one kind 2,2- difluoro methyl piperate
Preparation method, for solving the problems of the prior art.
For achieving the above object and other related purposes, the present invention provides the preparation side of one kind 2,2- difluoro methyl piperate
Method, comprises the steps：2,2- difluoro pepper acyl fluorides (II) and methyl alcohol are acted on, 2,2- difluoro is prepared by esterification
Methyl piperate (III), its reaction equation are as follows：
Preferably, the concrete grammar of the esterification is：Methyl alcohol is added drop-wise in 2,2- difluoro pepper acyl fluorides, has been reacted
Reactant liquor is added in alkaline aqueous solution after becoming, is extracted with organic solvent, separate and organic phase is obtained, precipitation, make after purification
Standby obtain 2,2- difluoro methyl piperate.
It is furthermore preferred that the alkaline aqueous solution selected from sodium bicarbonate aqueous solution, wet chemical, aqueous sodium carbonate,
The combination of one or more in sodium hydrate aqueous solution etc., the organic solvent selected from chloroform, dichloromethane, dichloroethanes,
The combination of one or more in ethyl acetate etc., the method for the purifying is distillation.
It is furthermore preferred that the temperature of the esterification is preferably in the range of at -10-240 DEG C, more preferably 20-70 DEG C,
The reaction time of esterification be 0.1-100 hour in, more preferably in 2-20 hour.
It is furthermore preferred that 1.0-50 times mole of the consumption of methyl alcohol for 2,2- difluoro pepper acyl fluorides, more preferably 1.0-5 times
Mole, more preferably 2-4 times mole.
Preferably, the preparation method of 2, the 2- difluoro pepper acyl fluorides is：By 2,2- dichloro pepper acyl chlorides (I) and hydrogen fluoride
Fluorination reaction is carried out, 2,2- difluoro pepper acyl fluorides (II) is obtained, reaction equation is as follows：
It is furthermore preferred that the concrete grammar of the fluorination reaction is：2,2- dichloro pepper acyl chlorides is placed in reaction vessel, so
After be passed through hydrogen fluoride and reacted, hydrogen fluoride is in the form of being passed through in batches or being disposably passed through.
It is furthermore preferred that 2-20 times mole of the usage amount of hydrogen fluoride for 2,2- dichloro pepper acyl chlorides, more preferably 3.0-
5.0 times of moles.
It is furthermore preferred that the temperature of fluorination reaction is preferably in the range of 30-120 DEG C, more preferably 50-70 DEG C, preferably
Reaction time is 0.1-100 hour, more preferably 2-20 hour.
Preferably, the preparation method of 2, the 2- dichloro pepper acyl chlorides is：With piperonal as raw material, draw in initiator or light
2,2- dichloro pepper acyl chlorides (I) are prepared with chlorinated with chlorine reaction in the presence of sending out, reaction equation is as follows：
Preferably, the concrete grammar of the chlorination reaction is：When chlorination reaction is caused using initiator, chlorine and will be dissolved in
The piperonal of reaction dissolvent, initiator are simultaneously introduced in reaction vessel；When using light-initiated chlorination reaction, chlorine and will be dissolved in
The piperonal of reaction dissolvent is simultaneously introduced in reaction vessel, and carries out illumination to reaction system；After chlorination reaction terminates, degassing,
Distillation, collects target fraction.
It is furthermore preferred that the ratio of the addition speed of piperonal is preferably 2-10 times in the addition speed of chlorine and reaction dissolvent
Mole, more preferably 2-5:1, most preferably 2-4:1.The mol ratio of chlorine and piperonal is preferably 2-10:1, more preferably
2-5:1, more preferably 2-4:1.
It is furthermore preferred that when chlorination reaction is caused with initiator, the initiator is different selected from azodiisobutyronitrile, azo two
The combination of one or more in valeronitrile, ABVN, two cyclohexanenitrile of azo, benzoyl peroxide etc., the initiator
Weight ratio with piperonal is 0.01%-5.0%：1.When light-initiated chlorination reaction is used, the light is preferably ultraviolet light.
It is furthermore preferred that the temperature of the chlorination reaction is 60-240 DEG C, and more preferably 80-150 DEG C, most preferably 120-
140℃.Faster reaction speed can be obtained at this temperature and generation tar is little.
The present invention further provides the preparation method of one kind 2,2- difluoro methyl piperate, comprises the steps：
1) chlorination reaction：With piperonal as raw material, initiator or light-initiated in the presence of prepare with chlorine reaction
2,2- dichloro pepper acyl chlorides, reaction equation are as follows：
2) fluorination reaction：2,2- dichloro pepper acyl chlorides (intermediate compound I) are carried out fluorination reaction with hydrogen fluoride, obtains 2,2- bis-
Fluorine pepper acyl fluorides (intermediate II), reaction equation is as follows：
3) esterification：2,2- difluoro pepper acyl fluorides and methyl alcohol are acted on, 2,2- difluoro methyl piperate is prepared, its
Reaction equation is as follows：
Main advantages of the present invention are as follows：
(1) synthetic route of the preparation method of 2,2- difluoro methyl piperate provided by the present invention is short, and technological process is easy
In control, completely, high income, the target product purity for preparing are high for reaction, and steady quality is complied fully with as agricultural chemicals or doctor
The use requirement of medicine intermediate.
(2) raw material used by the preparation method of 2,2- difluoro methyl piperate provided by the present invention and reagent cheap, tool
For body, raw material piperonal low price, chlorine and hydrogen fluoride are all low-cost basic chemical raw materials.
(3) solvent for use amount in each step reaction of the preparation method of 2,2- difluoro methyl piperate provided by the present invention
Few, generation waste liquid is few, and not only reduces cost reduces environmental pollution, is also highly convenient for large-scale commercial production.
Specific embodiment
Inventor sequentially passes through chlorination reaction, fluorination reaction, three step of esterification anti-with a piperonal as raw material
Acquisition 2,2- difluoro methyl piperate should be obtained, a kind of process is simple, reaction condition are gentle, intermediate need not be pure so as to provide
The preparation method of 2, the 2- difluoro methyl piperate of the high suitable industrial large-scale production of change, product quality, on this basis
Complete the present invention.
The present invention provides the preparation method of one kind 2,2- difluoro methyl piperate, comprises the steps：
1) chlorination reaction：With piperonal as raw material, initiator or light-initiated in the presence of prepare with chlorine reaction
2,2- dichloro pepper acyl chlorides, reaction equation are as follows：
Preferably, the concrete grammar of the chlorination reaction is：When chlorination reaction is caused using initiator, chlorine and will be dissolved in
The piperonal of reaction dissolvent, initiator are simultaneously introduced in reaction vessel；When using light-initiated chlorination reaction, chlorine and will be dissolved in
The piperonal of reaction dissolvent is simultaneously introduced in reaction vessel, and carries out illumination to reaction system；The addition speed of chlorine and reaction
In solvent, the ratio of the addition speed of piperonal is preferably 2-10 times of mole, more preferably 2-5:1, most preferably 2-4:1, this
Skilled person can control chlorine according to reaction process (the conversion situation of chlorine and piperonal in reaction system) monitoring result
The addition speed of gas and the reaction dissolvent containing piperonal.
In the step 1, spendable reaction dissolvent include but is not limited to benzene, chlorobenzene, dichloro-benzenes, fluorobenzene, benzotrifluoride,
P-chloro benzo trifluoride-99, dichloromethane, dichloroethanes, chloroform, carbon tetrachloride, fluoro trichloromethane, 1,1,2- trichloroethanes, 1,1-
Difluoro tetrachloroethanes, 1,2- difluoro tetrachloroethanes, seven fluoro- 2,3,3- tri- chlorobutanes, 1,1,1,3 ,-tetrachloro tetrafluoropropane, 1,1,
The combination of one or more in 1- trichloropentafluoropropane, 1,1,1- trichorotrifluoroethane, the consumption for reaction dissolvent do not have
Specifically limited, as long as the goal of the invention to the present invention does not produce restriction, it is preferred that the usage amount of reaction dissolvent is piperonal
0-20 times of weight, more preferably 1-5 times weight, in a preferred embodiment, the reaction dissolvent be to chlorine fluoroform
Benzene.When those skilled in the art can control the reaction of fluorination reaction according to reaction process (Expenditure Levels of raw material in reaction system)
Between, after chlorination reaction terminates, degassing, distillation, collect target fraction.In a preferred embodiment, target fraction is
134-136 DEG C/1.4KPa (document：145 DEG C/15mmHg, Yagupol'skii, L.M.；Zhurnal Obshchei Khimii
1960,V30,P3129-32).After chlorination reaction terminates, it is also possible to do not make any process, lower step fluorination reaction is direct plungeed into.
In the chlorination reaction of step (1), the mol ratio of chlorine and piperonal is preferably 2-10:1, more preferably 2-5:
1, more preferably 2-4:1, in a preferred embodiment, the mol ratio of chlorine and piperonal is 3:1.Chlorine and Hu
The mol ratio of green pepper aldehyde is typically corresponding with the ratio of the addition speed of chlorine and piperonal, i.e., when chlorine and the mol ratio of piperonal
After determination, the speed ratio which adds also is this ratio.
In step (1), chlorination reaction can be caused with initiator, it is also possible to light-initiated chlorination reaction.When with initiator
When causing chlorination reaction, the initiator can select the various chlorination reactions in this area initiator applicatory, specifically available
Initiator is included but is not limited to：Azodiisobutyronitrile, AMBN, ABVN, two cyclohexanenitrile of azo, peroxidating
The combination of one or more in benzoyl etc., in a preferred embodiment, the initiator is selected from two isobutyl of azo
Nitrile.When light-initiated chlorination reaction is used, preferably with ultraviolet light-initiated chlorination reaction.The initiator with the weight ratio of piperonal is
0.01%-5.0%：1, in a preferred embodiment, initiator is 0.1 with the mol ratio of piperonal:1.
In step (1).The temperature of chlorination reaction is 60-240 DEG C, more preferably 80-150 DEG C, most preferably 120-
140℃.Faster reaction speed can be obtained at this temperature and generation tar is little.
2) fluorination reaction：2,2- dichloro pepper acyl chlorides (intermediate compound I) are carried out fluorination reaction with hydrogen fluoride, obtains 2,2- bis-
Fluorine pepper acyl fluorides (intermediate II), reaction equation is as follows：
2,2- dichloro pepper acyl chlorides used in step (2) can be step (1) products therefrom, and the product can
2,2- of gained dichloro pepper acyl chlorides after thinking distillation purifying, or piperonal and chlorine carry out not making after chlorination reaction any
The product of gained is processed, can be direct plungeed in the fluorination reaction of step (2).
In step (2), the concrete grammar of fluorination reaction is：2,2- dichloro pepper acyl chlorides is placed in reaction vessel,
Then pass to hydrogen fluoride to be reacted, hydrogen fluoride can be passed through in batches, it is also possible to disposably be passed through.
In step (2), the usage amount of hydrogen fluoride is preferably 2-20 times of mole of 2,2- dichloro pepper acyl chlorides, more excellent
Elect 3.0-5.0 times of mole as.
In step (2), the temperature of fluorination reaction preferably in the range of 30-120 DEG C, more preferably 50-70 DEG C, this
Skilled person can control the reaction time of fluorination reaction according to reaction process, and the preferred reaction time is 0.1-100 hour,
More preferably 2-20 hour.
After fluorination reaction terminates, any process can not be made, direct plunge into lower step esterification.
3) esterification：2,2- difluoro pepper acyl fluorides and methyl alcohol are acted on, 2,2- difluoro methyl piperate is prepared, its
Reaction equation is as follows：
2,2- difluoro pepper acyl fluorides used in step (3) can be step (2) products therefrom, and the product is
2,2- dichloro pepper acyl chlorides do not make any product for processing gained after carrying out fluorination reaction with hydrogen fluoride, can direct plunge into step
(3) in esterification.
In step (3), the concrete grammar of esterification is：Methyl alcohol is added drop-wise in 2,2- difluoro pepper acyl fluorides, instead
Should after the completion of reactant liquor is added in alkaline aqueous solution, extracted with organic solvent, separate and obtain organic phase, precipitation, after purification
2,2- difluoro methyl piperate is prepared.The alkaline aqueous solution be preferably sodium bicarbonate aqueous solution, wet chemical,
The combination of one or more in aqueous sodium carbonate, sodium hydrate aqueous solution etc., more preferably saturated sodium bicarbonate aqueous solution,
In a preferred embodiment, the alkaline aqueous solution is 5wt% sodium bicarbonate aqueous solution.Those skilled in the art can root
Extracted from suitable organic solvent according to actual conditions, available organic solvent is included but is not limited to：Chloroform, dichloromethane
The combination of one or more in alkane, dichloroethanes, ethyl acetate etc..The purifying can select the various purification process in this area,
Preferably distill, those skilled in the art can determine whether the cut of target product, in a preferred embodiment, receive during distillation
Integrate boiling point as the cut of 118-120 DEG C/6KPa.
In step (3), the temperature of esterification is preferably in the range of at -10-240 DEG C, more preferably 20-100
DEG C, the esterification can also be carried out at room temperature, and in a preferred embodiment, reaction temperature is 70 DEG C.
In step (3), those skilled in the art can control the reaction time of esterification, esterification according to reaction process
The reaction time of reaction be 0.1-100 hour in, it is furthermore preferred that the reaction time is in 2-20 hour.
In step (3), the consumption of methyl alcohol is 1.0-50 times of mole of 2,2- difluoro pepper acyl fluorides, more preferably
1.0-5 times of mole, more preferably 2-4 times mole.Step (3) can be added without solvent, also can react molten
Reacted in agent.The reaction dissolvent is selected from the aliphatic solvent such as pentane, hexane, heptane, thiacyclohexane, petroleum ether, dichloromethane
Alkane, dichloroethanes, chloroform, ethyl acetate, isopropyl acetate, acetonitrile, propionitrile, benzene, toluene, ethylbenzene, dimethylbenzene, chlorobenzene, dichloro
Benzene, fluorobenzene, benzotrifluoride, nitrobenzene, ether, tetrahydrofuran, 2- methyltetrahydrofuran, glycol dimethyl ether, diethylene glycol two
The combination of one or more in methyl ether etc..Consumption in step (3) for reaction dissolvent is not particularly limited, as long as not
Goal of the invention to the present invention produces restriction, it is preferred that the usage amount of reaction dissolvent is 0-20 times of weight of piperonal, more
Preferably 0-2 times weight.
Further, since 2,2- dichloro pepper acyl chlorides (intermediate compound I, CAS：72769-07-4) He 2,2- difluoro pepper acyl fluorides
(intermediate II, CAS：656-44-0) known compound is, accordingly it is also possible to open using both intermediates as raw material respectively
Begin to prepare, obtain 2,2- difluoro methyl piperate product.
The present invention also provides the system of the preparation method in 2,2- difluoro methyl piperate of 2, the 2- difluoro methyl piperate
The purposes in standby field.
The preparation method synthetic route of 2,2- difluoro methyl piperate provided by the present invention is short, with low cost, technique stream
Journey is easily controllable, and completely, high income, the target product purity for preparing are high, steady quality, and low in the pollution of the environment, non-for reaction
Often it is suitable for large-scale industrial production.
Embodiments of the present invention are described below by way of specific instantiation, those skilled in the art can be by this specification
Disclosed content understands other advantages of the present invention and effect easily.The present invention can also pass through in addition different concrete realities
The mode of applying is carried out or applies, the every details in this specification can also based on different viewpoints and application, without departing from
Various modifications and changes are carried out under the spirit of the present invention.
It should be clear that in the following example the not concrete process equipment for indicating or device all using conventional equipment in the art or
Device；All pressure value and scope are all referring to absolute pressure.Unless otherwise indicated, otherwise all of number is molar part, owns
Percentage be weight percentage.
In addition, it is to be understood that the one or more method and steps that mentions in the present invention do not repel before and after the combination step
Can also there is additive method step or additive method step can also be inserted between the step of these specifically mention, unless separately
It is described；It should also be understood that the combination annexation between the one or more equipment/devices that mentions in the present invention is not repelled
Can also exist before and after the unit equipment/device other equipment/device or two equipment/devices specifically mentioning at these it
Between can also insert other equipment/device, unless otherwise stated.And, unless otherwise stated, the numbering of various method steps is only
Differentiate the convenient tool of various method steps, rather than for limiting the ordering of various method steps or limiting the enforceable model of the present invention
Enclose, being altered or modified for its relativeness, in the case of nothing substantially change technology contents, enforceable when the present invention is also considered as
Category.
Embodiment 1
The preparation of 2,2- dichloro pepper acyl chlorides
By after 300g piperonal, the mixing of 0.3g azodiisobutyronitrile and after 600g p-chloro benzo trifluoride-99 mixed dissolution, drip
Enter in reactor, while chlorine (total amount 426g) is passed through with the speed of 71g/ hour, and keep interior temperature 120-140 DEG C.Piperonal
About 6 hours completion of dropping of solution, reaction terminate.Decompression deaerates, then removed under reduced pressure p-chloro benzo trifluoride-99, then carries out decompression steaming
Evaporate, the cut of 134-136 DEG C/1.4kPa is collected, 2,2- dichloro pepper acyl chlorides 479g is obtained, the yield of chlorination reaction is 94.4%.
Embodiment 2
The preparation of 2,2- difluoro pepper acyl fluorides
479g 2,2- dichloro pepper acyl chlorides is put in polytetrafluoro reactor, reactor interior temperature is risen to 40 DEG C, under stirring
120g hydrogen fluoride is passed through, is stirred half an hour at 50-70 DEG C after having led to, reaction terminates.Measured by GC-MS method, reaction is produced
Thing is 2,2- difluoro pepper acyl fluorides.This reactant liquor is directly used as the next step.
Embodiment 3
The preparation of 2,2- difluoro methyl piperates
Above-mentioned reactant liquor is risen to 70 DEG C, then 128g methyl alcohol is dripped, after dripping, continue back flow reaction 1 hour, reaction
Terminate.After being cooled to room temperature, reactant liquor is transferred in the sodium bicarbonate solution containing 5% weight of 500g, divides after stirring half an hour
Liquid, organic phase anhydrous magnesium sulfate are transferred in rectifying still after filtering after drying.The cut of 118-120 DEG C/6KPa is collected, is obtained
2,2- difluoro methyl piperate 337g, fluorination esterification two-step reaction yield be 82.7%, 2,2- difluoro methyl piperates pure
Spend for 99.8%.
1H-NMR (CDCl3) δ 7.86 (d, 1H, J=8.3Hz)；7.70(m,1H)；7.10 (d, 1H, J=8.3Hz)；3.93
(s,3H).
19F-NMR(CDCl3)δ-49.7.
m/z：216(M+), 185,157,119,91,63.
In sum, the present invention effectively overcomes various shortcoming of the prior art and has high industrial utilization.
Above-described embodiment only principle of the illustrative present invention and its effect, not for the restriction present invention.Any ripe
The personage for knowing this technology all can carry out modifications and changes without prejudice under the spirit and the scope of the present invention to above-described embodiment.Cause
This, those of ordinary skill in the art is complete with institute under technological thought without departing from disclosed spirit such as
All equivalent modifications for becoming or change, must be covered by the claim of the present invention.
Claims (7)
1. the preparation method of 2,2- of one kind difluoro methyl piperate, comprises the steps：By 2,2- difluoro pepper acyl fluorides (II) and
Methyl alcohol is acted on, and prepares 2,2- difluoro methyl piperate (III) by esterification, and its reaction equation is as follows：
The preparation method of 2, the 2- difluoro pepper acyl fluorides is：2,2- dichloro pepper acyl chlorides (I) are carried out being fluorinated instead with hydrogen fluoride
Should, 2,2- difluoro pepper acyl fluorides (II) is obtained, reaction equation is as follows：
The preparation method of 2, the 2- dichloro pepper acyl chlorides is：With piperonal as raw material, initiator or light-initiated in the presence of
2,2- dichloro pepper acyl chlorides is prepared with chlorinated with chlorine reaction, reaction equation is as follows：
2. the preparation method of a kind of 2,2- difluoro methyl piperate as claimed in claim 1, it is characterised in that the esterification is anti-
The concrete grammar that answers is：Methyl alcohol is added drop-wise in 2,2- difluoro pepper acyl fluorides, reactant liquor is added to alkaline water after the completion of reaction
In solution, extracted with organic solvent, separate and organic phase is obtained, precipitation, prepare 2,2- difluoro methyl piperate after purification.
3. a kind of preparation method of 2,2- difluoro methyl piperate as claimed in claim 2, it is characterised in that the alkaline water
The one kind or many of solution in sodium bicarbonate aqueous solution, wet chemical, aqueous sodium carbonate, sodium hydrate aqueous solution etc.
The combination that plants；
And/or, the group that one or more in chloroform, dichloromethane, dichloroethanes, ethyl acetate etc. of the organic solvent
Close, the method for the purifying is distillation；
And/or, the temperature of the esterification be in the range of -10-240 DEG C；
And/or, the reaction time of esterification is in 0.1-100 hour；
And/or, the consumption of methyl alcohol is 1.0-50 times of mole of 2,2- difluoro pepper acyl fluorides.
4. the preparation method of a kind of 2,2- difluoro methyl piperate as claimed in claim 1, it is characterised in that the fluorination is anti-
The concrete grammar that answers is：2,2- dichloro pepper acyl chlorides is placed in reaction vessel, is then passed to hydrogen fluoride and is reacted.
5. a kind of preparation method of 2,2- difluoro methyl piperate as claimed in claim 4, it is characterised in that the making of hydrogen fluoride
Consumption is 2-20 times of mole of 2,2- dichloro pepper acyl chlorides；
And/or, hydrogen fluoride is in the form of being passed through in batches or being disposably passed through；
And/or, the temperature of fluorination reaction is preferably in the range of 30-120 DEG C；
And/or, the reaction time is 0.1-100 hour.
6. the preparation method of a kind of 2,2- difluoro methyl piperate as claimed in claim 1, it is characterised in that the chlorination is anti-
The concrete grammar that answers is：When causing chlorination reaction using initiator, by chlorine and be dissolved in the piperonal of reaction dissolvent, initiator with
When add reaction vessel in；When using light-initiated chlorination reaction, chlorine and the piperonal for being dissolved in reaction dissolvent are simultaneously introduced
In reaction vessel, and illumination is carried out to reaction system；After chlorination reaction terminates, degassing, distillation, collect target fraction.
7. a kind of preparation method of 2,2- difluoro methyl piperate as claimed in claim 6, it is characterised in that the addition of chlorine
In speed and reaction dissolvent, the ratio of the addition speed of piperonal is preferably 2-10 times of mole；
And/or, the mol ratio of chlorine and piperonal is preferably 2-10:1；
And/or, when chlorination reaction is caused with initiator, the initiator is selected from azodiisobutyronitrile, AMBN, idol
The combination of one or more in the different heptonitrile of nitrogen two, two cyclohexanenitrile of azo, benzoyl peroxide etc.；When anti-with light-initiated chlorination
Should, the light is ultraviolet light；
And/or, the temperature of the chlorination reaction is 60-240 DEG C.
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| DE3642256A1 (en) * | 1985-12-13 | 1987-06-19 | Byk Gulden Lomberg Chem Fab | Process for the preparation of fluorine-substituted 1,3-benzo- dioxoles |
| JP2003321406A (en) * | 2002-04-30 | 2003-11-11 | Mitsubishi Gas Chem Co Inc | High-purity fluoroalkylbenzene derivative and method for producing the same |
| BRPI0507278A (en) * | 2004-01-30 | 2007-06-26 | Vertex Pharma | modulators of atp-binding cassette transporters |
| CN102351704A (en) * | 2011-08-25 | 2012-02-15 | 浙江巍华化工有限公司 | Method for synthesizing methyl 3-(trifluoromethyl)benzoate |
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