CN103214355A - Method for preparing fluorine-containing methyl or alkylaryl ketones - Google Patents
Method for preparing fluorine-containing methyl or alkylaryl ketones Download PDFInfo
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Abstract
The invention discloses a method for preparing fluorine-containing methyl or alkylaryl ketones, belonging to an organic synthesis field. The method comprises two steps of: ester condensation: ester condensation reaction of an R1COOR2 compound represented by a formula A with a R2COOR2 compound represented by a formula B, is performed to form an R1COCH(R3)COOR2 intermediate represented by a formula C; and ester interchange: R1COCH(R3)COOR2 represented by the formula C is carried out ester interchange reaction with R2COOH under 100-110 DEG C and with catalysis of dilute H2SO4 or a cationic resin, and then decarboxylating to obtain R1COR2 fluorine-containing methyl or alkylaryl ketones represented by a formula D. The R1 group may be CF3-, CF2-, CF- or Ar-; the R2 group may be CH3-, Et- and n-Pr; and the R3 group may be CH3-, Et- and H-. Ester interchange in the invention avoids formation of HOR2 which has a nearly same boiling point with the compound represented by the formula D and is azeotropic with the compound represented by the formula D, enables the compound represented by the formula D to be purified without series rectification operation, and is suitable for large scale production. Simultaneously, ester interchange in the invention greatly raises cost. An ion exchange resin completes ester interchange in a waterless condition, which avoids a de-watering step, and simplifies technologies.
Description
Technical field
The invention belongs to the organic synthesis field, what be specifically related to is the method that preparation contains methyl fluoride or aryl alkyl ketone.
Background technology
Contain methyl fluoride or arylalkyl ketone compound, it is the important fluorine-containing organic synthesis intermediate of a class, and the aspect such as synthetic of the development of, aqueous vapor transmitter synthetic at medicine and nonlinear optical material has obtained application.In recent years, it is found that this compounds is the important intermediate of synthetic fluorinated liquid crystal material.In addition, this compounds is also opened up as the research work of some single Electron Transfer Reactions of electron acceptor(EA).
Its chemical structural formula is as follows:
The existing report of its synthetic route mainly is two lines.Be respectively: article one is a substrate to contain ethyl fluoroacetate, by the Claisen condensation, and hydrolysis, decarboxylation is finished synthetic; What J.BURDON group reported is example.
J.BURDON group (Tetrahedron, 1964,20,2163-6) report is that Trifluoroacetic Acid Ethyl Ester is a substrate, is solvent with ether, refluxes with ethyl propionate in the presence of sodium Metal 99.5, carries out the Claisen condensation and obtains intermediate CF
3COCMeNaCO
2Et; Intermediate CF
3COCMeNaCO
2Et refluxes in 30% sulfuric acid again, hydrolysis decarboxylation to CF
3COEt, its first step yield are that 34%, the second step yield is that 27%, two step total recovery only is 9.2%.Simultaneously because hydrolysis leaves away is ethanol and CF
3The COEt boiling point is close, and azeotropic can't further be purified.
Above-described is substrate to contain ethyl fluoroacetate, by the Claise condensation, and hydrolysis, there is following shortcoming in the preparation method of decarboxylation:
(1) adopt a large amount of ethers to make solvent, not only cost is too high, and reclaims difficulty, therefore in industrial production, can not reach optimization;
(2) two step yields are very low, the cost height.
(3) approaching owing to containing methyl fluoride or the most boiling point of arylalkyl ketone compound and ethanol, and the two azeotropic, therefore the ethanol of leaving away under acidic conditions can come out with the product azeotropic, is difficult to pass through rectification and purification.Can't obtain extremely pure methyl fluoride or the aryl alkyl ketone of containing.
Second also is to be that substrate prepares by Grignard reagent to contain ethyl fluoroacetate.What Sykes group reported is example.
Sykes group (Journal ofthe Chemical Society, 1956,835-9) report is to be substrate with the Trifluoroacetic Acid Ethyl Ester, at 10-15 ℃ of Grignard reagent that drips down with the EtMgI of Mg and EtI preparation, after cancellation, acidifying, extraction, rectifying, synthetic CF
3COEt.Yield is 52%.
To contain ethyl fluoroacetate is the preparation method of substrate by Grignard reagent, has following shortcoming:
(1) adopt a large amount of ethers to make solvent, not only cost is too high, and reclaims difficulty, therefore in industrial production, can not reach optimization;
(2) use Grignard reagent, require the anhydrous and oxygen-free operation, and have certain danger, increased the complicacy of technology, with difficulty.
(3) approaching owing to containing methyl fluoride or the most boiling point of arylalkyl ketone compound and ethanol, and the two azeotropic, therefore the ethanol of leaving away can come out with the product azeotropic, is difficult to pass through rectification and purification.Can't obtain extremely pure methyl fluoride or the aryl alkyl ketone of containing.
(4) iodoethane price height, production cost is higher.
Summary of the invention
The invention provides a kind of synthetic method that contains methyl fluoride or aryl alkyl ketone, is raw material to contain ethyl fluoroacetate, by ester condensation, and transesterify, decarboxylation is synthesized and is contained methyl fluoride or aryl alkyl ketone, and cost consumption is low, and is simple to operate, be convenient to purify, the productive rate height, GC purity can reach more than 98%.
In order to realize technical purpose of the present invention, technical scheme of the present invention is:
A kind of preparation contains the synthetic method of methyl fluoride or aryl alkyl ketone, the steps include:
Being main raw material shown in the formula A, under 0 ℃, be added drop-wise in the mixed solution of formula B and NaOR2, carry out ester condensation reaction at 60-70 ℃, generate suc as formula the intermediate shown in the C; Intermediate shown in the formula C under 100-110 ℃, is used the H of dilution
2SO
4Perhaps cation resin catalyzing, R2COOH carries out transesterification reaction, decarboxylation, the formula D of obtaining contains methyl fluoride or aryl alkyl ketone.Obtain formula B simultaneously;
Described R1 group is CF
3-, CF
2-, CF-, phenyl ring;
Described R2 group is CH
3-, CH
3CH
2-, CH
3CH
2CH
2-;
Described R3 group is CH
3-, CH
3CH
2-, H-.
Described formula A structural formula is as follows
Wherein, R1 is selected from and contains methyl fluoride, phenyl ring;
R2 is selected from the alkane of C1-C3;
Described formula B structural formula is as follows
Wherein, R2 is selected from the alkane of C1-C3.
The concrete steps of described method comprise:
(A) the first step reduces the temperature under 0 ℃, adds NaOR2, stirs 1h, drips formula A, is warmed up to 60-70 ℃, reaction 20-24h to raw material less than 1%;
After reaction finished, concentrating under reduced pressure transferred PH less than 2, extraction, and concentrating under reduced pressure, distillation obtains intermediate formula C;
(B) second step, at room temperature, the H for preparing
2SO
4Perhaps resin cation (R.C.) adds in the mixed solution of intermediate formula C and R2COOH, is warming up to 100-110 ℃ and carries out transesterification reaction;
Reaction dewaters after finishing, and rectifying obtains containing methyl fluoride or aryl alkyl ketone.
The amount of described NaOR2 be 1.1-2.0 suc as formula the mol ratio that contains ethyl fluoroacetate shown in the A.
The amount of described R2COOH be 0.3～1.5 suc as formula the intermediate mass ratio shown in the C.
Described H
2SO
4With the mass concentration of water be 15%-50%.
Described 98% H
2SO
4Amount be 0.1-0.3 suc as formula the mass ratio of the intermediate shown in the C.
The amount of described resin cation (R.C.) be 0.1-0.3 suc as formula the mass ratio of the intermediate shown in the C.
The beneficial effect that adopts technical scheme of the present invention to reach:
(1) the present invention has avoided processing condition such as the hazardous solvent in the currently known methods, risky operation, special device, can be used for amplifying producing.
(2) the present invention adopted transesterify in second step, not only solve the alcohol that generates in the reaction and product and contained the problem that methyl fluoride or aryl alkyl ketone azeotropic are difficult to purify, can obtain GC purity and reach pure product more than 98%, simultaneously, the raw material that ethanol is converted into the first step reaction can be directly used in the first step reaction, has saved cost greatly.
(3) Zeo-karb has been adopted in the present invention second step transesterify, and anhydrous system has been avoided the lower boiling product is contained the complicated technology that methyl fluoride or aryl alkyl ketone dewater.
(4) the present invention adds R2COOH in second step, carries out transesterify, has avoided generation and formula D boiling point to be close, azeotropic HOR2, and the formula D of making can purify, and need not harsh distillation operation, is convenient to carry out large-scale production; Simultaneously, the by-product formula B of generation can be used for the first step reaction, has improved cost greatly.The use of ion exchange resin made for second step can finish transesterify under anhydrous condition, avoided the finished product step that dewaters, and had simplified technology.
Description of drawings
Fig. 1 is 1,1-two fluoro-2-butanone
1H-NMR.
Fig. 2 is 1,1-two fluoro-2-butanone
13C-NMR.
Fig. 3 is a Propiophenone
1H-NMR.
Fig. 4 is a Propiophenone
13C-NMR.
Fig. 5 is 1,1,1-three fluoro-2 pentanones
1H-NMR.
Instrument model: JNM-ECX wherein, used condition is CDCl
3, 300K, AV-300;
Embodiment
Below in conjunction with specific examples technical scheme of the present invention is described further, but does not limit the present invention.
Of the present invention to the raw material Trifluoroacetic Acid Ethyl Ester, promptly to intermediate CF
3COCHMeCO
2Et and product 1,1, the detection method of 1-three fluoro-2-butanone is the GC method, its concrete testing conditions is as follows:
Instrument：GC-2010,SHIMADZU
Column：RTX-1,30.0m×0.25mm×0.25μm
SPL1：100℃
Column Oven Temp：
Detector：FID1
Temp：250℃
Hydrogen flow：40mL/min
Air flow： 450mL/min
Make up(N
2)： 20mL/min
Concrete raw material
Embodiment 1
2-ethyl-4,4, synthesizing of 4-trifluoroacetic ethyl acetoacetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add 90g butanic acid ethyl ester, be cooled to 0-5 ℃ with the cryosel bath, add the 26.3g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g Trifluoroacetic Acid Ethyl Ester, drip Bi Wendu and remain on 0-5 ℃ of following continuation stirring 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to TFAE＜1%, cooling, the butanic acid ethyl ester that concentrating under reduced pressure is excessive obtains brown solid, under 20 ℃, to wherein dripping 155g 3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 49.8g transparent liquid, yield 66.7%, purity: 94.2%(GC).
1,1,1-three fluoro-2 pentanones synthetic, in the four-hole boiling flask of 100ml, add 36g(94.2% successively) 2-ethyl-4,4, the 4-trifluoroacetic ethyl acetoacetate, 14.5g 50% sulfuric acid, the 36g butanic acid is taken water distilling apparatus, coolant temperature remains on below-5 ℃, stirs, and is warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1,1,1-three fluoro-2 pentanone crude products, to 2-ethyl-4,4, the 4-trifluoroacetic ethyl acetoacetate＜1%, cooling obtains the colourless transparent liquid crude product, to wherein adding P
2O
5Dewater, rectifying obtains 14.5g1, and 1,1-three fluoro-2 pentanones, yield 63.5%, purity: 99.20%(GC).
1,1,1-three fluoro-2 pentanones synthetic, in the four-hole boiling flask of 100ml, add 36g(94.2% successively) 2-ethyl-4,4, the 4-trifluoroacetic ethyl acetoacetate, 7.2g Zeo-karb Amberlyst-15, the 36g butanic acid is taken water distilling apparatus, coolant temperature remains on below-5 ℃, stirs, and is warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1,1,1-three fluoro-2 pentanone crude products, to 2-ethyl-4,4,4-trifluoroacetic ethyl acetoacetate＜1%, cooling, obtain the colourless transparent liquid crude product, rectifying obtains 16.7g1, and 1,1-three fluoro-2 pentanones, yield 75.2%, purity: 98.40%(GC).
Embodiment 2
4,4, synthesizing of 4-trifluoroacetic ethyl acetoacetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add the 69.0g ethyl acetate, be cooled to 0-5 ℃ with the cryosel bath, add the 26.3g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g Trifluoroacetic Acid Ethyl Ester, drip Bi Wendu and remain on 0-5 ℃ of following continuation stirring 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to TFAE＜1%, cooling, the ethyl acetate that concentrating under reduced pressure is excessive obtains brown solid, under 20 ℃, to wherein dripping 155g3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 45.8g transparent liquid, yield 70.7%, purity: 96.8%(GC).
1,1,1-three fluoro-2-acetone synthetic, in the four-hole boiling flask of 100ml, add 36g(94.2% successively) 4,4, the 4-trifluoroacetic ethyl acetoacetate, 14.5g 50% sulfuric acid, 36g acetate is taken water distilling apparatus, coolant temperature remains on below-5 ℃, stirs, and is warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1,1,1-three fluoro-2-acetone crude products, to 4,4, the 4-trifluoroacetic ethyl acetoacetate＜1%, cooling obtains the colourless transparent liquid crude product, to wherein adding P
2O
5Dewater, rectifying obtains 12.8g 1,1,1-three fluoro-2-acetone, yield 60.5%, purity: 98.20%(GC).
Embodiment 3
2-methyl-4, synthesizing of 4-difluoro methyl aceto acetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add the 90.5g ethyl propionate, be cooled to 0-5 ℃ with the cryosel bath, add the 30.1g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g ethyl difluoro, a Bi Wendu remain on 0-5 ℃ to be continued down to stir 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to DFAE＜1%, cooling, the ethyl propionate that concentrating under reduced pressure is excessive, obtain brown solid, under 20 ℃, to wherein dripping 155g 3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 58.2g transparent liquid, yield 80.0%, purity: 97.3%(GC).
1,1-two fluoro-2-butanone synthetic adds 36g(97.3% successively in the four-hole boiling flask of 100ml) 2-methyl-4,4-difluoro methyl aceto acetate, the sulfuric acid of 14.5g 50%, 36g propionic acid, take water distilling apparatus, coolant temperature remains on below-5 ℃, stirs, and is warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1,1-two fluoro-2-butanone crude products, to 2-methyl-4,4-difluoro methyl aceto acetate＜1%, cooling obtains the colourless transparent liquid crude product, to wherein adding P
2O
5Dewater, rectifying obtains 16.2g1,1-two fluoro-2-butanone, yield 77.2%, purity: 98.8%(GC).
Embodiment 4
2-ethyl-4, synthesizing of 4-difluoro methyl aceto acetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add 103g butanic acid ethyl ester, be cooled to 0-5 ℃ with the cryosel bath, add the 30.1g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g ethyl difluoro, a Bi Wendu remain on 0-5 ℃ to be continued down to stir 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to DFAE＜1%, cooling, the butanic acid ethyl ester that concentrating under reduced pressure is excessive, obtain brown solid, under 20 ℃, to wherein dripping 155g 3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 59.6g transparent liquid, yield 75.4%, purity: 97.2%(GC).
1, synthesizing of 1-two fluoro-2 pentanones adds the 2-ethyl-4 of 36g (97.2%) successively in the four-hole boiling flask of 100ml, 4-difluoro methyl aceto acetate, 14.5g 50% sulfuric acid, the 36g butanic acid is taken water distilling apparatus, coolant temperature remains on below-5 ℃, stir, be warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1,1-two fluoro-2 pentanone crude products, to 2-ethyl-4,4-difluoro methyl aceto acetate＜1%, cooling, obtain the colourless transparent liquid crude product, dewater to wherein adding P2O5, rectifying obtains 16.7g1,1-two fluoro-2-butanone, yield 76.2%, purity: 98.5%(GC).
Embodiment 5
4, synthesizing of 4-difluoro methyl aceto acetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add the 78.7g ethyl acetate, be cooled to 0-5 ℃ with the cryosel bath, add the 30.1g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g ethyl difluoro, a Bi Wendu remain on 0-5 ℃ to be continued down to stir 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to DFAE＜1%, cooling, the ethyl acetate that concentrating under reduced pressure is excessive, obtain brown solid, under 20 ℃, to wherein dripping 155g3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 53.0g transparent liquid, yield 79.1%, purity: 97.5%(GC).
1,1-two fluoro-2-acetone synthetic adds 36g(97.5% successively in the four-hole boiling flask of 100ml) 4,4-difluoro methyl aceto acetate, the sulfuric acid of 14.5g 50%, 36g acetate, take water distilling apparatus, coolant temperature remains on below-5 ℃, stirs, and is warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1,1-two fluoro-2-acetone crude products, to 4,4-difluoro methyl aceto acetate＜1%, cooling obtains the colourless transparent liquid crude product, to wherein adding P
2O
5Dewater, rectifying obtains 14.3g 1,1-two fluoro-2-acetone, yield 72.2%, purity: 98.3%(GC).
Embodiment 6
Synthesizing of 2-methyl-4-acetyl fluoride ethyl acetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add the 105.8g ethyl propionate, be cooled to 0-5 ℃ with the cryosel bath, add the 35.3g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g ethyl fluoroacetate, drip Bi Wendu and remain on 0-5 ℃ of following continuation stirring 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to ethyl fluoroacetate＜1%, cooling, the ethyl propionate that concentrating under reduced pressure is excessive obtains brown solid, under 20 ℃, to wherein dripping 155g 3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 56.2g transparent liquid, yield 73.6%, purity: 94.6%(GC).
Synthesizing of 1-fluoro-2-butanone, in the four-hole boiling flask of 100ml, add 36g(94.6% successively) 2-methyl-4-acetyl fluoride ethyl acetate, the sulfuric acid of 14.5g50%, the 36g propionic acid, take water distilling apparatus, coolant temperature remains on below-5 ℃, stirs, and is warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1-fluoro-2-butanone crude product, to 2-methyl-4-acetyl fluoride ethyl acetate＜1%, cooling obtains the colourless transparent liquid crude product, dewater to wherein adding P2O5, rectifying obtains 13.7g 1-fluoro-2-butanone, yield 70.7%, purity: 98.20%(GC).
Embodiment 7
Synthesizing of 2-ethyl-4-acetyl fluoride ethyl acetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add 120.4g butanic acid ethyl ester, be cooled to 0-5 ℃ with the cryosel bath, add the 35.3g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g ethyl fluoroacetate, drip Bi Wendu and remain on 0-5 ℃ of following continuation stirring 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to ethyl fluoroacetate＜1%, cooling, the butanic acid ethyl ester that concentrating under reduced pressure is excessive obtains brown solid, under 20 ℃, to wherein dripping 155g 3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 58.6g transparent liquid, yield 70.6%, purity: 93.4%(GC).
Synthesizing of 1-fluoro-2 pentanone, in the four-hole boiling flask of 100ml, add 36g(93.4% successively) 2-ethyl-4-acetyl fluoride ethyl acetate, 14.5g 50% sulfuric acid, the 36g butanic acid is taken water distilling apparatus, and coolant temperature remains on below-5 ℃, stir, be warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1-fluoro-2-butanone crude product, to 2-ethyl-4-acetyl fluoride ethyl acetate＜1%, cooling obtains the colourless transparent liquid crude product, to wherein adding P
2O
5Dewater, rectifying obtains 14.1g1-fluoro-2 pentanone, yield 69.2%, purity: 98.0% (GC).
Synthesizing of 4-acetyl fluoride ethyl acetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add the 91.3g ethyl acetate, be cooled to 0-5 ℃ with the cryosel bath, add the 35.3g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g ethyl fluoroacetate, drip Bi Wendu and remain on 0-5 ℃ of following continuation stirring 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to ethyl fluoroacetate＜1%, cooling, the ethyl acetate that concentrating under reduced pressure is excessive obtains brown solid, under 20 ℃, to wherein dripping 155g3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 45.7g transparent liquid, yield 65.6%, purity: 93.2%(GC).
Synthesizing of 1-fluoro-2-acetone, in the four-hole boiling flask of 100ml, add 36g(93.2% successively) 4-acetyl fluoride ethyl acetate, the sulfuric acid of 14.5g50%, 36g acetate is taken water distilling apparatus, and coolant temperature remains on below-5 ℃, stir, be warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1-fluoro-2-butanone crude product, to 2-ethyl-4-acetyl fluoride ethyl acetate＜1%, cooling obtains the colourless transparent liquid crude product, to wherein adding P
2O
5Dewater, rectifying obtains 11.0g 1-fluoro-2-acetone, yield 60.2%, purity: 98.0%(GC).
Embodiment 9
Synthesizing of 2-methylbenzene methyl aceto acetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add 50g phenylacetyl ethyl acetate, 150gDMF, add 50g ground salt of wormwood, stirred 0.5 hour under the room temperature, be warmed up to 40 ℃, drip the mixed solution of 41.3g methyl iodide and 50gDMF, drip and finish, be warmed up to 60-65 ℃ of insulation 3h, do not have raw material to GC, cooling is poured in the 2L frozen water, with the 800mlEA extraction, revolve EA, obtain the 45.7g brown liquid, yield 85.6%, purity: 95.2%(GC).
Propiophenone synthetic adds 36g(95.2% successively in the four-hole boiling flask of 100ml) 2-methylbenzene methyl aceto acetate, the sulfuric acid of 14.5g50%, take water distilling apparatus, stir, be warmed up to 100-110 ℃ of reaction down, the limit reaction, the limit steams ethanol, to 2-methylbenzene methyl aceto acetate＜1%, cooling obtains light brown liquid, uses the 36g dichloromethane extraction, revolve methylene dichloride, obtain the 19.9g Propiophenone, yield 90.2%, purity: 98.6%(GC).
Embodiment 10
2-methyl-4, synthesizing of 4-difluoro methyl acetoacetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add the 78.5g methyl propionate, be cooled to 0-5 ℃ with the cryosel bath, add the 30.1g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g ethyl difluoro, a Bi Wendu remain on 0-5 ℃ to be continued down to stir 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to DFAE＜1%, cooling, the methyl propionate that concentrating under reduced pressure is excessive, obtain brown solid, under 20 ℃, to wherein dripping 155g 3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 52.9g transparent liquid, yield 79.0%, purity: 97.8%(GC).
1,1-two fluoro-2-butanone synthetic adds 36g(97.8% successively in the four-hole boiling flask of 100ml) 2-methyl-4,4-difluoro methyl acetoacetate, the sulfuric acid of 14.5g50%, 36g propionic acid, take water distilling apparatus, coolant temperature remains on below-5 ℃, stirs, and is warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1,1-two fluoro-2-butanone crude products, to 2-methyl-4,4-difluoro methyl acetoacetate＜1%, cooling obtains the colourless transparent liquid crude product, to wherein adding P
2O
5Dewater, rectifying obtains 17.1g1,1-two fluoro-2-butanone, yield 75.2%, purity: 98.2%(GC).
1,1-two fluoro-2-butanone synthetic, in the four-hole boiling flask of 100ml, add 36g(97.8% successively) 2-methyl-4,4-difluoro methyl acetoacetate, 7.2g Zeo-karb Amberlyst-15, the 36g propionic acid is taken water distilling apparatus, and coolant temperature remains on below-5 ℃, stir, be warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1,1-two fluoro-2-butanone crude products, to 2-methyl-4,4-difluoro methyl acetoacetate＜1%, cooling obtains the colourless transparent liquid crude product, rectifying obtains 17.9g 1,1-two fluoro-2-butanone, yield 78.9%, purity: 98.90%(GC).
Synthesizing of 2-methyl-4-acetyl fluoride methyl acetate, in the anhydrous exsiccant four-hole boiling flask of 250ml, add the 91.3g methyl propionate, be cooled to 0-5 ℃ with the cryosel bath, add the 35.3g solid sodium ethanol, stirred 1 hour down at 0-5 ℃, Dropwise 5 0g ethyl fluoroacetate, drip Bi Wendu and remain on 0-5 ℃ of following continuation stirring 1 hour, be warmed up to 60-65 ℃, under 60-65 ℃, stir 24 hours to ethyl fluoroacetate＜1%, cooling, the methyl propionate that concentrating under reduced pressure is excessive obtains brown solid, under 20 ℃, to wherein dripping 155g 3NHCl to PH≤2.Use 100mL1,2-ethylene dichloride extracting twice concentrates, and obtains brown oily crude product, and crude product rectifying obtains the 49.1g transparent liquid, yield 70.4%, purity: 94.6%(GC).
Synthesizing of 1-fluoro-2-butanone, in the four-hole boiling flask of 100ml, add 36g(94.6% successively) 2-methyl-4-acetyl fluoride methyl acetate, 14.5g 50% sulfuric acid, the 36g propionic acid is taken water distilling apparatus, and coolant temperature remains on below-5 ℃, stir, be warmed up to 100-110 ℃ of reaction down, the limit coronite distills out 1-fluoro-2-butanone crude product, to 2-methyl-4-acetyl fluoride methyl acetate＜1%, cooling obtains the colourless transparent liquid crude product, to wherein adding P
2O
5Dewater, rectifying obtains 14.4g 1-fluoro-2-butanone, yield 68.7%, purity: 98.70 (GC).
Claims (9)
1. one kind prepares the method that contains methyl fluoride or aryl alkyl ketone, the steps include:
(A) ester condensation: under 0 ℃, the compound shown in the formula A be the compound shown in main raw material and the formula B in the mixed solution of NaOR2, carry out ester condensation reaction, generate suc as formula the intermediate shown in the C;
(B) transesterify: the intermediate shown in the formula C under 100-110 ℃, is used the H of dilution
2SO
4Perhaps cation resin catalyzing carries out R
2COOH transesterification reaction and decarboxylation obtain suc as formula containing methyl fluoride or aryl alkyl ketone shown in the D;
Described R1 group is CF
3-, CF
2-, CF-, phenyl ring;
Described R2 group is CH
3-, CH
3CH
2-, CH
3CH
2CH
2-;
Described R3 group is CH
3-, CH
3CH
2-, H-.
2. method according to claim 1 is characterized in that: the concrete steps of described method comprise,
(A) ester condensation: reduce the temperature under 0 ℃, add NaOR2, stir 1h, drip the compound shown in the formula A, be warmed up to 60-70 ℃, reaction 20-24h to raw material less than 1%, obtain suc as formula the intermediate shown in the C;
(B) second step, at room temperature, the H for preparing
2SO
4Perhaps resin cation (R.C.) adds intermediate formula C and R
2In the mixed solution of COOH, be warming up to 100-110 ℃ and carry out transesterification reaction, obtain.
3. method according to claim 2 is characterized in that:
After described step (A) reaction finished, concentrating under reduced pressure transferred PH less than 2, extraction, and concentrating under reduced pressure, distillation obtains suc as formula the intermediate shown in the C.
4. method according to claim 2 is characterized in that: after described step (B) reaction finishes, dewater, rectifying obtains containing methyl fluoride or aryl alkyl ketone.
5. according to any described method of claim 1 to 4, it is characterized in that: the amount of described NaOR2 be 1.1-2.0 suc as formula the mol ratio that contains ethyl fluoroacetate shown in the A.
6. according to any described method of claim 1 to 4, it is characterized in that: the amount of described R2COOH be 0.3～1.5 suc as formula the intermediate mass ratio shown in the C.
7. according to any described method of claim 1 to 4, it is characterized in that: described H
2SO
4With the mass concentration of water be 15%-50%.
8. according to any described method of claim 1 to 4, it is characterized in that: described 98% H
2SO
4Amount be 0.1-0.3 suc as formula the mass ratio of the intermediate shown in the C.
9. according to any described method of claim 1 to 4, it is characterized in that: the amount of described resin cation (R.C.) be 0.1-0.3 suc as formula the mass ratio of the intermediate shown in the C.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105001085A (en) * | 2015-04-26 | 2015-10-28 | 衢州学院 | Method for synthesizing ethyl 4,4-difluoroacetoacetate in catalyzed mode through layered materials |
| CN105820043A (en) * | 2016-04-26 | 2016-08-03 | 南通宝凯化工有限公司 | Production technique of difluoroacetone |
| WO2022233129A1 (en) | 2021-05-05 | 2022-11-10 | Fujian Yongjing Technology Co., Ltd | New process for the synthesis of 5-fluoro-3- (difuoromethyl) -5-fluoro-1-methyl-1h-pyrazole-4-carboxylic acid derivatives and the free acid thereof |
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| US5481029A (en) * | 1993-04-27 | 1996-01-02 | Solvay Fluor Und Derivate Gmbh | Process for preparation of ketones |
| CN102476984A (en) * | 2010-11-23 | 2012-05-30 | 中化蓝天集团有限公司 | Method for preparing 1,1,1-trifluoroacetone |
| CN102633644A (en) * | 2012-04-06 | 2012-08-15 | 华远医药研究院有限公司 | Synthesis process of trifluoroacetyl ethyl acetate |
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2012
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| US5481029A (en) * | 1993-04-27 | 1996-01-02 | Solvay Fluor Und Derivate Gmbh | Process for preparation of ketones |
| CN102476984A (en) * | 2010-11-23 | 2012-05-30 | 中化蓝天集团有限公司 | Method for preparing 1,1,1-trifluoroacetone |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105001085A (en) * | 2015-04-26 | 2015-10-28 | 衢州学院 | Method for synthesizing ethyl 4,4-difluoroacetoacetate in catalyzed mode through layered materials |
| CN105820043A (en) * | 2016-04-26 | 2016-08-03 | 南通宝凯化工有限公司 | Production technique of difluoroacetone |
| WO2022233129A1 (en) | 2021-05-05 | 2022-11-10 | Fujian Yongjing Technology Co., Ltd | New process for the synthesis of 5-fluoro-3- (difuoromethyl) -5-fluoro-1-methyl-1h-pyrazole-4-carboxylic acid derivatives and the free acid thereof |
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| CN103214355B (en) | 2016-02-17 |
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