CN107935853A - A kind of preparation method of fluoromalonic acid diester - Google Patents
A kind of preparation method of fluoromalonic acid diester Download PDFInfo
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- CN107935853A CN107935853A CN201711146238.5A CN201711146238A CN107935853A CN 107935853 A CN107935853 A CN 107935853A CN 201711146238 A CN201711146238 A CN 201711146238A CN 107935853 A CN107935853 A CN 107935853A
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/313—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
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Abstract
The present invention relates to organic synthesis field, more particularly to a kind of preparation method of fluoromalonic acid diester.The present invention provides a kind of preparation method of fluoromalonic acid diester, and the preparation method includes：Fluoroacetate and dialkyl carbonate are subjected to condensation reaction in the presence of a base, prepare fluoromalonic acid diester.The preparation method reaction process of fluoromalonic acid diester provided by the invention is gentleer, because having abandoned the chlorination fluorination step of routine, toxicity and corrosivity are low, are also produced without two fluoro diester malonate impurity, reaction requires relatively low, production process safety easy to operate to shop equipment.
Description
Technical field
The present invention relates to organic synthesis field, more particularly to a kind of preparation method of fluoromalonic acid diester.
Background technology
Fluoromalonic acid diester is a kind of important fluorine-containing organic intermediate, can carry out a series of alkylation, alcoxyl
Base, hydroxyalkylation etc. react, and are widely used in the production of organic synthesis, medicine, pesticide, spices, dyestuff etc., therefore, fluoro
Diester malonate derivative has extremely wide field and boundless development prospect, develops a kind of high benefit, low cost
Fluoromalonic acid diester synthesis technique be of great significance.
At this stage, the method for preparing fluoromalonic acid diester is mainly the following：Carbonyl elimination approach, esterification process, cracking
Method and fluoride process.
At present, most domestic producer is using hydrogen fluoride salts fluoride process.I.e. using malonic acid dimethyl (second) ester as raw material,
Target product is prepared through superchlorination, hydrogen fluoride triethylamine salt fluorination two-step reaction.The major defect of this method is raw material
Toxicity is big, strong to equipment corrosion, consersion unit is more demanding, and reaction process can produce dichloro- malonate and two fluoro third
Two acid diesters, influence product quality and yield.In addition in last handling process, triethylamine recycling is difficult and produces a large amount of nitrogenous useless
Water, processing trouble, and larger pollution is caused to environment.
In addition, Chinese patent (CN 1025318) provides a kind of method for preparing diethyl fluoromalonate, this method
Using fluoroacetic ethyl ester and diethy-aceto oxalate as initial feed, carry out synthesizing fluoro malonic acid two by being condensed, aoxidizing two steps
The problem of ethyl ester, total recovery 32.5%, it is relatively low that this method still has yield, and " three wastes " are more.
Therefore, this area be badly in need of developing a kind of step is brief, materials safety, environmentally protective more convenient easy and cost compared with
The method of synthesizing fluoro diester malonate that is low, being easy to industrialized production.
The content of the invention
In view of the foregoing deficiencies of prior art, it is an object of the invention to provide a kind of system of fluoromalonic acid diester
Preparation Method, for solving the problems of the prior art.
In order to achieve the above objects and other related objects, the present invention provides a kind of fluoromalonic acid diester (formula III chemical combination
Thing) preparation method, the preparation method includes：
Fluoroacetate (compound of formula I) and dialkyl carbonate (Formula II compound) are carried out in the presence of a base
Condensation reaction, prepares fluoromalonic acid diester, and the Formulas I, Formula II, the structural formula of formula III compound are as follows：
Wherein, R1, R2, R3 are methyl at the same time or are ethyl at the same time.
In some embodiments of the invention, the molar ratio of the fluoroacetate and dialkyl carbonate is 1: 1~20.
In some embodiments of the invention, the alkali is selected from alkaline metal organic salt, alkali carbonate, sodium hydride or ammonia
One or more combinations in base sodium.
In some embodiments of the invention, the alkaline metal organic salt is selected from sodium methoxide, potassium methoxide, sodium ethoxide, ethanol
One or more combinations in potassium, sodium tert-butoxide, potassium tert-butoxide, n-BuLi, diisopropylamine lithium (LDA).
In some of the invention embodiments, the alkali carbonate in sodium carbonate, lithium carbonate, potassium carbonate one
Kind or a variety of combinations.
In some embodiments of the invention, the molar ratio of the fluoroacetate and alkali is 1: 1~5.
In some embodiments of the invention, the molar ratio of the fluoroacetate and alkali is 1: 1~3.
In some embodiments of the invention, reaction temperature is 0~150 DEG C.
In some embodiments of the invention, reaction temperature is 80~120 DEG C.
In some embodiments of the invention, reaction carries out in the presence of a solvent, and the solvent is selected from organic molten
Agent.
In some embodiments of the invention, the solvent is selected from ether solvent.
In some embodiments of the invention, the ether solvent is selected from ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran, first
One or more combinations in base tetrahydrofuran.
In some embodiments of the invention, the post processing of the reaction includes：After the completion of reaction, reaction system is adjusted
PH value is 5~8, and organic phase precipitation is up to fluoromalonic acid diester.
In some embodiments of the invention, the post processing of the reaction further includes：By the temperature adjustment of reaction system to-
10~50 DEG C.
In some embodiments of the invention, the pH value of reaction system, the pH adjusting agent choosing are adjusted using pH adjusting agent
From one or more combinations in hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid.
Embodiment
Inventor passes through a large amount of explorative experiments, there is provided a kind of preparation method of new fluoromalonic acid diester,
The preparation method reaction condition is gentle, toxicity and corrosivity are low, and is easier to post-process, and is a kind of suitable heavy industrialization
The preparation method of production, completes the present invention on this basis.
The present invention provides a kind of preparation method of fluoromalonic acid diester (formula III compound), and the preparation method includes：
Fluoroacetate (compound of formula I) and dialkyl carbonate (Formula II compound) are carried out in the presence of a base
Condensation reaction, prepares fluoromalonic acid diester, and the Formulas I, Formula II, the structural formula of formula III compound are as follows：
In preparation method provided by the present invention, R1, R2, R3 can be each independently selected from alkyl, more specifically can be
Such as C1~C6 alkyl, C1~C3 alkyl etc., in the embodiment of the invention, described R1, R2, R3 can be each independent
Ground is selected from methyl or ethyl.In another embodiment of the present invention, the group of described R1, R2, R3 are identical.
In preparation method provided by the present invention, the alkali can usually provide the alkaline condition in reaction system, described
Alkali can be alkaline metal organic salt, alkali carbonate, sodium hydride or Sodamide etc..The alkaline metal organic salt is often referred to I A
The salts substances that the element of race is formed with organic compound, such as can be sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, uncle
One or more combinations in sodium butoxide, potassium tert-butoxide, n-BuLi, diisopropylamine lithium (LDA) etc..The alkali metal carbon
Hydrochlorate is often referred to the element of group ia and carbonic acid with the salts substances that are formed, such as can be from sodium carbonate, lithium carbonate or carbon
Sour potassium etc..In a preferred embodiment of the invention, the alkali is preferably selected from sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, hydrogen
Change sodium etc., be more preferably selected from potassium methoxide and/or potassium ethoxide.Those skilled in the art can be according on target product ester group to be prepared
Alkyl species select corresponding alkoxide, the alkali for such as preparing fluoromalonic acid dimethyl ester is preferably sodium methoxide and/or potassium methoxide, more
Preferably potassium methoxide, the alkali for preparing diethyl fluoromalonate are preferably sodium ethoxide and/or potassium ethoxide, more preferably potassium ethoxide.
The usage amount of the alkali is typically basic equivalent or excess by molar amount relative to fluoroacetate, for example, fluoro second
The molar ratio of acid esters and alkali can be 1: 1~5, or 1: 1~3.
In preparation method provided by the present invention, reaction temperature can be 0~150 DEG C, can also be 80~120 DEG C.This
Field technology personnel can suitably adjust the reaction time according to reaction process, monitor the method for reaction process for people in the art
It should be known for member, such as can be the analysis methods such as chromatography, nuclear magnetic resonance method, usually, can also be with original
The terminal that material substrate disappears as reaction substantially, when the specific reaction time can be that for example 1-10 is small.
In preparation method provided by the present invention, reaction can carry out in the presence of a solvent, and the solvent is usual
Can be organic solvent, more specifically can be ether organic solvent, ether solvent can be for example ether, methyl tertiary butyl ether(MTBE),
One or more combinations in tetrahydrofuran, methyltetrahydrofuran etc..Those skilled in the art can be according to the kind of reaction substrate
The species and dosage of class and dosage adjustment solvent, the usage amount of ether solvent can be 3~10 times of fluoroacetate weight.
In preparation method provided by the present invention, the dosage by molar amount dialkyl carbonate relative to fluoroacetate
Typically basic equivalent or excess, for example, the molar ratio of fluoroacetate and dialkyl carbonate can be 1: 1~20,
It is preferred that can be 1: 3~10.When react in solvent (for example, ether solvent) it is existing under the conditions of carrying out when, fluoroacetate with
The molar ratio of dialkyl carbonate can be 1：3~6；, can be by increasing carbonic acid two when not adding solvent in reaction system
The mode of Arrcostab dosage obtains more preferable reaction effect, such as the molar ratio of fluoroacetate and dialkyl carbonate can be
1：5~10.
In preparation method provided by the present invention, the post processing of the reaction can include：After the completion of reaction, reaction is adjusted
The pH value of system is 5~8, and preferable pH value is 6~7, and organic phase precipitation is up to fluoromalonic acid diester.In post processing, usually
Need to reduce the temperature of reaction system, for example, can be by the temperature adjustment of reaction system to -10~50 DEG C, for another example can be with
The temperature of reaction system is adjusted before the pH value of reaction system is adjusted.The reagent of pH value for adjusting reaction system can be
The various pH adjusting agents in this area, for example, pH adjusting agent can be selected from one or more in hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid etc.
Combination, preferably using acetic acid and/or aqueous hydrochloric acid solution.
The preparation method reaction process of fluoromalonic acid diester provided by the invention is gentleer, because having abandoned the chlorine of routine
Change fluorination step, toxicity and corrosivity are low, also without two fluoro diester malonate impurity produce, react to shop equipment requirement compared with
It is low, production process safety easy to operate.In addition, the whole reaction process of preparation method does not have nitrogenous effluent generation, save
Cost for wastewater treatment, also reduces the pollution of sewage discharge generation.
Illustrate embodiments of the present invention below by way of specific instantiation, those skilled in the art can be by this specification
Disclosed content understands other advantages and effect of the present invention easily.The present invention can also pass through in addition different specific realities
The mode of applying is embodied or practiced, the various details in this specification can also be based on different viewpoints with application, without departing from
Various modifications or alterations are carried out under the spirit of the present invention.
It should be clear that in the following example not specifically dated process equipment or device using conventional equipment in the art or
Device.
In addition, it should also be understood that, one or more method and step mentioned in the present invention does not repel before and after the combination step
Other methods step can also can also be inserted into there are other methods step or between the step of these are specifically mentioned, unless separately
It is described；It should also be understood that the combination connection relation between one or more equipment/device mentioned in the present invention is not repelled
The two equipment/devices that can also be specifically mentioned before and after the unit equipment/device there are other equipment/device or at these it
Between can also be inserted into other equipment/device, unless otherwise indicated.Moreover, unless otherwise indicated, the numbering of various method steps is only
Differentiate the convenient tool of various method steps, rather than ordering or the enforceable model of the restriction present invention for limitation various method steps
Enclose, its relativeness is altered or modified, and in the case where changing technology contents without essence, when being also considered as, the present invention is enforceable
Category.
Embodiment 1
The preparation of fluoromalonic acid dimethyl ester：
In 250m1 round-bottomed flasks, 80.0g dimethyl carbonates and 5.4g sodium methoxides are added, is heated to flowing back, fluorine second is added dropwise
Sour methyl esters 9.0g, reacts 2h.PH=6~7 being adjusted with 30% hydrochloric acid reaction being quenched, liquid separation, organic phase vacuum distillation, obtains fluoro
Dimethyl malenate 8.3g (content 96.5%), yield 54.6%.
Embodiment 2
The preparation of fluoromalonic acid dimethyl ester：
In 250m1 round-bottomed flasks, 40g tetrahydrofurans, 40.0g dimethyl carbonates and 10.8g sodium methoxides are added, is heated to
Reflux, is added dropwise methylfluoracetate 9.0g, reacts 4h.Reacted with 30% hydrochloric acid, liquid separation, organic phase vacuum distillation, obtains fluorine
For dimethyl malenate 8.3g (content 94.2%), yield 53.3%.
Embodiment 3
The preparation of fluoromalonic acid dimethyl ester：
In 250m1 round-bottomed flasks, 80.0g dimethyl carbonates and 7.0g potassium methoxides are added, is heated to flowing back, fluorine second is added dropwise
Sour methyl esters 9.0g, reacts 2h.Reacted with 30% hydrochloric acid, liquid separation, organic phase vacuum distillation, obtains fluoromalonic acid dimethyl ester
9.1g (content 98.0%), yield 60.8%.
Embodiment 4
The preparation of diethyl fluoromalonate：
In 250m1 round-bottomed flasks, 80.0g diethyl carbonates and 4.5g sodium hydrides are added, is heated to flowing back, fluorine second is added dropwise
Acetoacetic ester 9.0g, reacts 2h.Reacted with 30% hydrochloric acid, liquid separation, organic phase vacuum distillation, obtains diethyl fluoromalonate
9.1g (content 86.9%), yield 52.3%.
Embodiment 5
The preparation of diethyl fluoromalonate：
In 250m1 round-bottomed flasks, 80.0g diethyl carbonates and 10.8g potassium ethoxides are added, is heated to flowing back, fluorine is added dropwise
Ethyl acetate 9.0g, reacts 2h.Reacted with 30% hydrochloric acid, liquid separation, organic phase vacuum distillation, obtains fluoromalonic acid diethyl
Ester 10.3g (content 96.1%), yield 65.5%.
In conclusion the present invention effectively overcomes various shortcoming of the prior art and has high industrial utilization.
The above-described embodiments merely illustrate the principles and effects of the present invention, not for the limitation present invention.It is any ripe
Know the personage of this technology all can carry out modifications and changes under the spirit and scope without prejudice to the present invention to above-described embodiment.Cause
This, those of ordinary skill in the art is complete without departing from disclosed spirit and institute under technological thought such as
Into all equivalent modifications or change, should by the present invention claim be covered.
Claims (10)
1. a kind of preparation method of fluoromalonic acid diester, the preparation method include：
Fluoroacetate and dialkyl carbonate are subjected to condensation reaction in the presence of a base, prepare fluoromalonic acid
Diester, the structural formula of the fluoroacetate, dialkyl carbonate and fluoromalonic acid diester is respectively such as Formulas I, Formula II, formula III
It is shown：
Wherein, R1, R2, R3 are methyl at the same time or are ethyl at the same time.
A kind of 2. preparation method of fluoromalonic acid diester as claimed in claim 1, it is characterised in that the fluoroacetate
Molar ratio with dialkyl carbonate is 1: 1~20, is preferably 1：3~6 or 1：5~10.
3. a kind of preparation method of fluoromalonic acid diester as claimed in claim 1, it is characterised in that the alkali is selected from alkali gold
Belong to one or more combinations in organic salt, alkali carbonate, sodium hydride or Sodamide.
4. a kind of preparation method of fluoromalonic acid diester as claimed in claim 3, it is characterised in that the alkali metal is organic
Salt is in sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, n-BuLi, diisopropylamine lithium
One or more combinations, one or more groups of the alkali carbonate in sodium carbonate, lithium carbonate or potassium carbonate
Close.
A kind of 5. preparation method of fluoromalonic acid diester as claimed in claim 1, it is characterised in that the fluoroacetate
Molar ratio with alkali is 1: 1~5, is preferably 1: 1~3.
A kind of 6. preparation method of fluoromalonic acid diester as claimed in claim 1, it is characterised in that reaction temperature for 0~
150 DEG C, be preferably 80~120 DEG C.
7. a kind of preparation method of fluoromalonic acid diester as claimed in claim 1, it is characterised in that reaction exists in solvent
Under conditions of carry out, the solvent is selected from ether solvent.
A kind of 8. preparation method of fluoromalonic acid diester as claimed in claim 7, it is characterised in that the ether solvent choosing
From one or more combinations in ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran, methyltetrahydrofuran.
A kind of 9. preparation method of fluoromalonic acid diester as claimed in claim 1, it is characterised in that the rear place of the reaction
Reason includes：After the completion of reaction, the pH value for adjusting reaction system is 5~8, and organic phase precipitation is up to fluoromalonic acid diester.
10. a kind of preparation method of fluoromalonic acid diester as claimed in claim 9, it is characterised in that after the reaction
Processing further includes：By the temperature adjustment of reaction system to -10~50 DEG C.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110437069A (en) * | 2019-08-21 | 2019-11-12 | 凯莱英生命科学技术(天津)有限公司 | The method for continuously synthesizing of 2- fluorine diester malonate class compound |
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| US4694110A (en) * | 1985-05-13 | 1987-09-15 | Mitsui Toatsu Chemicals, Inc. | Process for production of m-phenoxybenzyl alcohol |
| CN107056606A (en) * | 2017-06-09 | 2017-08-18 | 浙江工业大学 | A kind of preparation method of 3 fluoropyruvate |
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2017
- 2017-11-17 CN CN201711146238.5A patent/CN107935853A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4694110A (en) * | 1985-05-13 | 1987-09-15 | Mitsui Toatsu Chemicals, Inc. | Process for production of m-phenoxybenzyl alcohol |
| CN107056606A (en) * | 2017-06-09 | 2017-08-18 | 浙江工业大学 | A kind of preparation method of 3 fluoropyruvate |
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| 赵坤等: "氟代丙二酸二乙酯的制备", 《有机氟工业》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110437069A (en) * | 2019-08-21 | 2019-11-12 | 凯莱英生命科学技术(天津)有限公司 | The method for continuously synthesizing of 2- fluorine diester malonate class compound |
| CN110437069B (en) * | 2019-08-21 | 2022-04-01 | 凯莱英生命科学技术(天津)有限公司 | Continuous synthesis method of 2-fluoro-malonic diester compound |
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Effective date of registration: 20200429 Address after: No. 336, yulinhe street, Lanzhou New District, Lanzhou City, Gansu Province Applicant after: Lanzhou kangpengweier Chemical Co., Ltd Address before: 224555 Coastal Industrial Park, Yancheng City Binhai Economic Development Zone, Jiangsu, China Applicant before: BINHAI KANGJIE CHEMICAL Co.,Ltd. Applicant before: JIANGSU WEIER CHEMICAL Co.,Ltd. |
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Application publication date: 20180420 |