CN103214355B - A kind of method prepared containing methyl fluoride or aryl alkyl ketone - Google Patents
A kind of method prepared containing methyl fluoride or aryl alkyl ketone Download PDFInfo
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- CN103214355B CN103214355B CN201210433824.9A CN201210433824A CN103214355B CN 103214355 B CN103214355 B CN 103214355B CN 201210433824 A CN201210433824 A CN 201210433824A CN 103214355 B CN103214355 B CN 103214355B
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Abstract
The invention discloses a kind of method prepared containing methyl fluoride or aryl alkyl ketone, belong to organic synthesis field.Step be divided into two steps for: ester condensation: carry out ester condensation reaction with R2COOR2 compound shown in the compound of R1COOR2 shown in formula A and formula B, generates the intermediate such as formula R1COCH shown in C (R3) COOR2; Transesterify: by R1COCH shown in formula C (R3) COOR2 at 100-110 DEG C, with the H of dilution
2sO
4or cation resin catalyzing, R2COOH carries out transesterification reaction, decarboxylation, obtains R1COR2 shown in formula D containing methyl fluoride or aryl alkyl ketone.Described R1 group is CF
3-, CF
2-, CF-, Ar-; Described R2 group is CH
3-, Et-, n-Pr; Described R3 group is CH
3-,? Et-, H-.Transesterify of the present invention, avoid generation and be close with formula D boiling point, the HOR2 of azeotropic, the formula D of making can purify, and without the need to the distillation operation of harshness, are convenient to carry out large-scale production; Meanwhile, cost is substantially increased.Ion exchange resin completes transesterify in anhydrous conditions, avoids water removal phase, Simplified flowsheet.
Description
Technical field
The invention belongs to organic synthesis field, what be specifically related to is the method that preparation contains methyl fluoride or aryl alkyl ketone.
Background technology
Containing methyl fluoride or arylalkyl ketone compound, it is the important fluorine-containing organic synthesis intermediate of a class, in the development of pharmaceutical synthesis, vapor sensor and the synthesis of nonlinear optical material etc., obtain application.In recent years, it is found that this compounds is the important intermediate of synthesis 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:
Its synthetic route has been reported, mainly two lines.Respectively: Article 1 is to contain ethyl fluoroacetate for substrate, and by Claisen condensation, be hydrolyzed, decarboxylation completes synthesis; What J.BURDON group reported is example.
What J.BURDON group (Tetrahedron, 1964,20,2163-6) reported is Trifluoroacetic Acid Ethyl Ester is substrate, take ether as solvent, refluxes, carry out Claisen condensation and obtain intermediate CF under sodium Metal 99.5 exists with ethyl propionate
3cOCMeNaCO
2et; Intermediate CF
3cOCMeNaCO
2et, then reflux in 30% sulfuric acid, hydrolysis decarboxylation to CF
3cOEt, its first step yield is 34%, and second step yield is that 27%, two step total recoverys are only 9.2%.That leave away due to hydrolysis is ethanol and CF simultaneously
3cOEt boiling point is close, azeotropic, cannot purify further.
Above-described to contain ethyl fluoroacetate for substrate, by Claise condensation, hydrolysis, there is following shortcoming in the preparation method of decarboxylation:
(1) adopt a large amount of ether to make solvent, not only high cost, and reclaim difficulty, therefore in the industrial production, can not optimization be reached;
(2) two step yields are very low, and cost is high.
(3) due to containing methyl fluoride or the most boiling point of arylalkyl ketone compound and ethanol close, and the two azeotropic, the ethanol of therefore leaving away in acid condition can with product azeotropic out, be difficult to pass through rectification and purification.Cannot obtain extremely pure containing methyl fluoride or aryl alkyl ketone.
Article 2 is also to be prepared by Grignard reagent for substrate containing ethyl fluoroacetate.What Sykes group reported is example.
What Sykes group (JournaloftheChemicalSociety, 1956,835-9) reported is take Trifluoroacetic Acid Ethyl Ester as substrate, the Grignard reagent of the EtMgI that dropping Mg and EtI prepares at 10-15 DEG C, by cancellation, and acidifying, extraction, rectifying, synthesis CF
3cOEt.Yield is 52%.
To contain ethyl fluoroacetate for substrate is by the preparation method of Grignard reagent, there is following shortcoming:
(1) adopt a large amount of ether to make solvent, not only high cost, and reclaim difficulty, therefore in the industrial production, can not optimization be reached;
(2) use Grignard reagent, require that anhydrous and oxygen-free operates, and there is certain danger, add the complicacy of technique, with difficulty.
(3) due to containing methyl fluoride or the most boiling point of arylalkyl ketone compound and ethanol close, and the two azeotropic, the ethanol of therefore leaving away can with product azeotropic out, be difficult to pass through rectification and purification.Cannot obtain extremely pure containing methyl fluoride or aryl alkyl ketone.
(4) iodoethane price is high, and production cost is higher.
Summary of the invention
The invention provides a kind of method that synthesis contains methyl fluoride or aryl alkyl ketone, to contain ethyl fluoroacetate for raw material, by ester condensation, transesterify, decarboxylation, synthesis is containing methyl fluoride or aryl alkyl ketone, and cost consumption is low, simple to operate, be convenient to purify, productive rate is high, and GC purity can reach more than 98%.
In order to realize technical purpose of the present invention, technical scheme of the present invention is:
Prepare the synthetic method containing methyl fluoride or aryl alkyl ketone, the steps include:
With shown in formula A for main raw material, at 0 DEG C, be added drop-wise in the mixed solution of formula B and NaOR2, carry out ester condensation reaction at 60-70 DEG C, generate such as formula the intermediate shown in C; By the intermediate shown in formula C at 100-110 DEG C, with the H of dilution
2sO
4or cation resin catalyzing, R2COOH carries out transesterification reaction, decarboxylation, obtains formula D containing 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 containing 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, at reducing the temperature to 0 DEG C, adds NaOR2, stirs 1h, drips formula A, is warmed up to 60-70 DEG C, and reaction 20-24h is less than 1% to raw material;
After reaction terminates, concentrating under reduced pressure, adjust PH to be less than 2, extraction, concentrating under reduced pressure, distillation, obtains intermediate formula C;
(B) second step, at room temperature, the H prepared
2sO
4or resin cation (R.C.) adds in the mixed solution of intermediate formula C and R2COOH, be warming up to 100-110 DEG C and carry out transesterification reaction;
After reaction terminates, dewater, rectifying, obtains containing methyl fluoride or aryl alkyl ketone.
The amount of described NaOR2 be 1.1-2.0 such as formula the mol ratio containing ethyl fluoroacetate shown in A.
The amount of described R2COOH be 0.3 ~ 1.5 such as formula the intermediate mass ratio shown in C.
Described H
2sO
4be 15%-50% with the mass concentration of water.
The H of described 98%
2sO
4amount be 0.1-0.3 such as formula the mass ratio of the intermediate shown in C.
The amount of described resin cation (R.C.) is 0.1-0.3 with the mass ratio such as formula the intermediate shown in C.
Adopt the beneficial effect that technical scheme of the present invention reaches:
(1) present invention, avoiding the processing condition such as the hazardous solvent in currently known methods, risky operation, special device, may be used for amplifying and produce.
(2) second step of the present invention adopts transesterify, not only solve the problem that the alcohol that generates in reaction and product are difficult to containing methyl fluoride or aryl alkyl ketone azeotropic purify, the sterling that GC purity reaches more than 98% can be obtained, simultaneously, raw material ethanol being converted into the first step reaction can be directly used in the first step reaction, has greatly saved cost.
(3) second step transesterify of the present invention, have employed Zeo-karb, anhydrous system, avoids the complicated technology dewatered containing methyl fluoride or aryl alkyl ketone to lower boiling product.
(4) the present invention adds R2COOH in second step, carries out transesterify, avoids to generate to be close with formula D boiling point, and the HOR2 of azeotropic, the formula D of making can purify, and without the need to the distillation operation of harshness, are convenient to carry out large-scale production; Meanwhile, the by-product formula B of generation, may be used for the first step reaction, substantially increases cost.The use of ion exchange resin, makes second step can complete transesterify in anhydrous conditions, avoids the finished product water removal phase, simplify technique.
Accompanying drawing explanation
Fig. 1 is the fluoro-2-butanone of 1,1-bis-
1h-NMR.
Fig. 2 is the fluoro-2-butanone of 1,1-bis-
13c-NMR.
Fig. 3 is Propiophenone
1h-NMR.
Fig. 4 is Propiophenone
13c-NMR.
Fig. 5 is the fluoro-2 pentanone of 1,1,1-tri-
1h-NMR.
Wherein INSTRUMENT MODEL: JNM-ECX, condition used 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 raw material Trifluoroacetic Acid Ethyl Ester, namely to intermediate CF
3cOCHMeCO
2the detection method of Et and the fluoro-2-butanone of product 1,1,1-tri-is GC method, and its concrete testing conditions is as follows:
Instrument：GC-2010,SHIMADZU
Column：RTX-1,30.0m×0.25mm×0.25μm
SPL1：100℃
ColumnOvenTemp：
Detector：FID1
Temp：250℃
Hydrogenflow：40mL/min
Airflow：450mL/min
Makeup(N
2)：20mL/min
Concrete raw material
Embodiment 1
2-ethyl-4,4, the synthesis of 4-trifluoroacetic ethyl acetoacetate, 90g ethyl butyrate is added in the four-hole boiling flask of the anhydrous drying of 250ml, be cooled to 0-5 DEG C with cryosel bath, add 26.3g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g Trifluoroacetic Acid Ethyl Ester, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stir 24 little of TFAE<1%, cooling, the ethyl butyrate that concentrating under reduced pressure is excessive, obtains brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 49.8g transparent liquid, yield 66.7%, purity: 94.2%(GC).
The synthesis of the fluoro-2 pentanone of 1,1,1-tri-, in the four-hole boiling flask of 100ml, add 36g(94.2% successively) 2-ethyl-4,4,4-trifluoroacetic ethyl acetoacetate, the sulfuric acid of 14.5g50%, 36g butanic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stirs, react at being warmed up to 100-110 DEG C, limit coronite distills out the fluoro-2 pentanone crude product of 1,1,1-tri-, to 2-ethyl-4,4,4-trifluoroacetic ethyl acetoacetate <1%, cooling, obtain colourless transparent liquid crude product, add P wherein
2o
5dewater, rectifying obtains 14.5g1, the fluoro-2 pentanone of 1,1-tri-, yield 63.5%, purity: 99.20%(GC).
1, 1, the synthesis of the fluoro-2 pentanone of 1-tri-, in the four-hole boiling flask of 100ml, add 36g(94.2% successively) 2-ethyl-4, 4, 4-trifluoroacetic ethyl acetoacetate, 7.2g Zeo-karb Amberlyst-15, 36g butanic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stir, react at being warmed up to 100-110 DEG C, limit coronite distills out 1, 1, the fluoro-2 pentanone crude product of 1-tri-, to 2-ethyl-4, 4, 4-trifluoroacetic ethyl acetoacetate <1%, cooling, obtain colourless transparent liquid crude product, rectifying obtains 16.7g1, 1, the fluoro-2 pentanone of 1-tri-, yield 75.2%, purity: 98.40%(GC).
Embodiment 2
4,4, the synthesis of 4-trifluoroacetic ethyl acetoacetate, 69.0g ethyl acetate is added in the four-hole boiling flask of the anhydrous drying of 250ml, be cooled to 0-5 DEG C with cryosel bath, add 26.3g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g Trifluoroacetic Acid Ethyl Ester, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stir 24 little of TFAE<1%, cooling, the ethyl acetate that concentrating under reduced pressure is excessive, obtains brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 45.8g transparent liquid, yield 70.7%, purity: 96.8%(GC).
The synthesis of the fluoro-2-acetone of 1,1,1-tri-, adds 36g(94.2% successively in the four-hole boiling flask of 100ml) 4,4,4-trifluoroacetic ethyl acetoacetate, the sulfuric acid of 14.5g50%, 36g acetic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stirs, and reacts at being warmed up to 100-110 DEG C, limit coronite distills out 1,1,1-tri-fluoro-2-acetone crude product, to 4,4,4-trifluoroacetic ethyl acetoacetate <1%, cooling, obtains colourless transparent liquid crude product, adds P wherein
2o
5dewater, rectifying obtains 12.8g1, the fluoro-2-acetone of 1,1-tri-, yield 60.5%, purity: 98.20%(GC).
Embodiment 3
2-methyl-4, the synthesis of 4-difluoro methyl aceto acetate, 90.5g ethyl propionate is added in the four-hole boiling flask of the anhydrous drying of 250ml, 0-5 DEG C is cooled to cryosel bath, add 30.1g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g ethyl difluoro, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stirring 24 is little of DFAE<1%, cooling, the ethyl propionate that concentrating under reduced pressure is excessive, obtain brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 58.2g transparent liquid, yield 80.0%, purity: 97.3%(GC).
The synthesis of the fluoro-2-butanone of 1,1-bis-, 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 14.5g50%, 36g propionic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stirs, react at being warmed up to 100-110 DEG C, limit coronite distills out the fluoro-2-butanone crude product of 1,1-bis-, to 2-methyl-4,4-difluoro methyl aceto acetate <1%, cooling, obtain colourless transparent liquid crude product, add P wherein
2o
5dewater, rectifying obtains 16.2g1, the fluoro-2-butanone of 1-bis-, yield 77.2%, purity: 98.8%(GC).
Embodiment 4
2-ethyl-4, the synthesis of 4-difluoro methyl aceto acetate, 103g ethyl butyrate is added in the four-hole boiling flask of the anhydrous drying of 250ml, 0-5 DEG C is cooled to cryosel bath, add 30.1g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g ethyl difluoro, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stirring 24 is little of DFAE<1%, cooling, the ethyl butyrate that concentrating under reduced pressure is excessive, obtain brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 59.6g transparent liquid, yield 75.4%, purity: 97.2%(GC).
1, the synthesis of the fluoro-2 pentanone of 1-bis-, in the four-hole boiling flask of 100ml, add 36g(97.2% successively) 2-ethyl-4, 4-difluoro methyl aceto acetate, the sulfuric acid of 14.5g50%, 36g butanic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stir, react at being warmed up to 100-110 DEG C, limit coronite distills out 1, the fluoro-2 pentanone crude product of 1-bis-, to 2-ethyl-4, 4-difluoro methyl aceto acetate <1%, cooling, obtain colourless transparent liquid crude product, add P2O5 wherein to dewater, rectifying obtains 16.7g1, the fluoro-2-butanone of 1-bis-, yield 76.2%, purity: 98.5%(GC).
Embodiment 5
4, the synthesis of 4-difluoro methyl aceto acetate, 78.7g ethyl acetate is added in the four-hole boiling flask of the anhydrous drying of 250ml, 0-5 DEG C is cooled to cryosel bath, add 30.1g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g ethyl difluoro, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stirring 24 is little of DFAE<1%, cooling, the ethyl acetate that concentrating under reduced pressure is excessive, obtain brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 53.0g transparent liquid, yield 79.1%, purity: 97.5%(GC).
The synthesis of the fluoro-2-acetone of 1,1-bis-, adds 36g(97.5% successively in the four-hole boiling flask of 100ml) 4,4-difluoro methyl aceto acetate, the sulfuric acid of 14.5g50%, 36g acetic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stirs, react at being warmed up to 100-110 DEG C, limit coronite distills out 1,1-bis-fluoro-2-acetone crude product, to 4,4-difluoro methyl aceto acetate <1%, cooling, obtain colourless transparent liquid crude product, add P wherein
2o
5dewater, rectifying obtains 14.3g1, the fluoro-2-acetone of 1-bis-, yield 72.2%, purity: 98.3%(GC).
Embodiment 6
The synthesis of 2-methyl-4-acetyl fluoride ethyl acetate, 105.8g ethyl propionate is added in the four-hole boiling flask of the anhydrous drying of 250ml, 0-5 DEG C is cooled to cryosel bath, add 35.3g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g ethyl fluoroacetate, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stir 24 little of ethyl fluoroacetate <1%, cooling, the ethyl propionate that concentrating under reduced pressure is excessive, obtains brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 56.2g transparent liquid, yield 73.6%, purity: 94.6%(GC).
The synthesis of the fluoro-2-butanone of 1-, 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%, 36g propionic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stir, react at being warmed up to 100-110 DEG C, limit coronite distills out the fluoro-2-butanone crude product of 1-, to 2-methyl-4-acetyl fluoride ethyl acetate <1%, cooling, obtain colourless transparent liquid crude product, add P2O5 wherein to dewater, rectifying obtains the fluoro-2-butanone of 13.7g1-, yield 70.7%, purity: 98.20%(GC).
Embodiment 7
The synthesis of 2-ethyl-4-acetyl fluoride ethyl acetate, 120.4g ethyl butyrate is added in the four-hole boiling flask of the anhydrous drying of 250ml, 0-5 DEG C is cooled to cryosel bath, add 35.3g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g ethyl fluoroacetate, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stir 24 little of ethyl fluoroacetate <1%, cooling, the ethyl butyrate that concentrating under reduced pressure is excessive, obtain brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 58.6g transparent liquid, yield 70.6%, purity: 93.4%(GC).
The synthesis of the fluoro-2 pentanone of 1-, adds 36g(93.4% successively in the four-hole boiling flask of 100ml) 2-ethyl-4-acetyl fluoride ethyl acetate, the sulfuric acid of 14.5g50%, 36g butanic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stirs, react at being warmed up to 100-110 DEG C, limit coronite distills out the fluoro-2-butanone crude product of 1-, to 2-ethyl-4-acetyl fluoride ethyl acetate <1%, and cooling, obtain colourless transparent liquid crude product, add P wherein
2o
5dewater, rectifying obtains the fluoro-2 pentanone of 14.1g1-, yield 69.2%, purity: 98.0% (GC).
Embodiment 8
The synthesis of 4-acetyl fluoride ethyl acetate, 91.3g ethyl acetate is added in the four-hole boiling flask of the anhydrous drying of 250ml, 0-5 DEG C is cooled to cryosel bath, add 35.3g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g ethyl fluoroacetate, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stir 24 little of ethyl fluoroacetate <1%, cooling, the ethyl acetate that concentrating under reduced pressure is excessive, obtains brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 45.7g transparent liquid, yield 65.6%, purity: 93.2%(GC).
The synthesis of the fluoro-2-acetone of 1-, adds 36g(93.2% successively in the four-hole boiling flask of 100ml) 4-acetyl fluoride ethyl acetate, the sulfuric acid of 14.5g50%, 36g acetic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stirs, react at being warmed up to 100-110 DEG C, limit coronite distills out the fluoro-2-butanone crude product of 1-, to 2-ethyl-4-acetyl fluoride ethyl acetate <1%, and cooling, obtain colourless transparent liquid crude product, add P wherein
2o
5dewater, rectifying obtains the fluoro-2-acetone of 11.0g1-, yield 60.2%, purity: 98.0%(GC).
Embodiment 9
The synthesis of 2-methylbenzene methyl aceto acetate, adds 50g phenylacetyl ethyl acetate, 150gDMF in the four-hole boiling flask of the anhydrous drying of 250ml, add the salt of wormwood that 50g grinds, stirred at ambient temperature 0.5 hour, is warmed up to 40 DEG C, drip the mixed solution of 41.3g methyl iodide and 50gDMF, drip and finish, be warmed up to 60-65 DEG C of insulation 3h, to GC without raw material, cooling, pours in 2L frozen water, with 800mlEA extraction, revolve EA, obtain 45.7g brown liquid, yield 85.6%, purity: 95.2%(GC).
The synthesis of Propiophenone, 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, react at being warmed up to 100-110 DEG C, limit is reacted, while steam ethanol, to 2-methylbenzene methyl aceto acetate <1%, cooling, obtains light brown liquid, uses 36g dichloromethane extraction, revolve methylene dichloride, obtain 19.9g Propiophenone, yield 90.2%, purity: 98.6%(GC).
Embodiment 10
2-methyl-4, the synthesis of 4-difluoro methyl acetoacetate, 78.5g methyl propionate is added in the four-hole boiling flask of the anhydrous drying of 250ml, 0-5 DEG C is cooled to cryosel bath, add 30.1g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g ethyl difluoro, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stirring 24 is little of DFAE<1%, cooling, the methyl propionate that concentrating under reduced pressure is excessive, obtain brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 52.9g transparent liquid, yield 79.0%, purity: 97.8%(GC).
The synthesis of the fluoro-2-butanone of 1,1-bis-, 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 less than-5 DEG C, stirs, react at being warmed up to 100-110 DEG C, limit coronite distills out the fluoro-2-butanone crude product of 1,1-bis-, to 2-methyl-4,4-difluoro methyl acetoacetate <1%, cooling, obtain colourless transparent liquid crude product, add P wherein
2o
5dewater, rectifying obtains 17.1g1, the fluoro-2-butanone of 1-bis-, yield 75.2%, purity: 98.2%(GC).
1, the fluoro-2-butanone of 1-bis-synthesis, 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, 36g propionic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stir, react at being warmed up to 100-110 DEG C, limit coronite distills out 1, the fluoro-2-butanone crude product of 1-bis-, to 2-methyl-4, 4-difluoro methyl acetoacetate <1%, cooling, obtain colourless transparent liquid crude product, rectifying obtains 17.9g1, the fluoro-2-butanone of 1-bis-, yield 78.9%, purity: 98.90%(GC).
Embodiment 11
The synthesis of 2-methyl-4-acetyl fluoride methyl acetate, 91.3g methyl propionate is added in the four-hole boiling flask of the anhydrous drying of 250ml, 0-5 DEG C is cooled to cryosel bath, add 35.3g solid sodium ethanol, stir 1 hour at 0-5 DEG C, drip 50g ethyl fluoroacetate, drip at Bi Wendu remains on 0-5 DEG C and continue stirring 1 hour, be warmed up to 60-65 DEG C, at 60-65 DEG C, stir 24 little of ethyl fluoroacetate <1%, cooling, the methyl propionate that concentrating under reduced pressure is excessive, obtains brown solid, at 20 DEG C, drip 155g3NHCl to PH≤2 wherein.By 100mL1,2-ethylene dichloride extracting twice, concentrated, obtain brown oil crude product, crude product rectifying obtains 49.1g transparent liquid, yield 70.4%, purity: 94.6%(GC).
The synthesis of the fluoro-2-butanone of 1-, adds 36g(94.6% successively in the four-hole boiling flask of 100ml) 2-methyl-4-acetyl fluoride methyl acetate, the sulfuric acid of 14.5g50%, 36g propionic acid, take water distilling apparatus, coolant temperature remains on less than-5 DEG C, stirs, react at being warmed up to 100-110 DEG C, limit coronite distills out the fluoro-2-butanone crude product of 1-, to 2-methyl-4-acetyl fluoride methyl acetate <1%, and cooling, obtain colourless transparent liquid crude product, add P wherein
2o
5dewater, rectifying obtains the fluoro-2-butanone of 14.4g1-, yield 68.7%, purity: 98.70 (GC).
Claims (9)
1. prepare the method containing methyl fluoride or aryl alkyl ketone, the steps include:
(A) ester condensation: at 0 DEG C, the compound shown in formula A, for the compound shown in main raw material and formula B is in the mixed solution of NaOR2, carries out ester condensation reaction, generates such as formula the intermediate shown in C;
(B) transesterify: by the intermediate shown in formula C at 100-110 DEG C, with the H of dilution
2sO
4or cation resin catalyzing, carries out R2COOH transesterification reaction and decarboxylation, obtain such as formula shown in D containing methyl fluoride or aryl alkyl ketone;
Described R1 group is CF
3-, CF
2-, CF-, phenyl ring;
Described R2 group is CH
3cH
2-, CH
3cH
2cH
2-;
Described R3 group is CH
3-, CH
3cH
2-.
2. method according to claim 1, is characterized in that: the concrete steps of described method comprise,
(A) ester condensation: at reducing the temperature to 0 DEG C, add NaOR2, stirs 1h, drips the compound shown in formula A, is warmed up to 60-70 DEG C, and reaction 20-24h is less than 1% to raw material, obtains such as formula the intermediate shown in C;
(B) second step, at room temperature, the H prepared
2sO
4or resin cation (R.C.) adds in the mixed solution of intermediate formula C and R2COOH, be warming up to 100-110 DEG C and carry out transesterification reaction, obtain.
3. method according to claim 2, is characterized in that:
After described step (A) reaction terminates, concentrating under reduced pressure, adjust PH to be less than 2, extraction, concentrating under reduced pressure, distillation, obtains such as formula the intermediate shown in C.
4. method according to claim 2, is characterized in that: after described step (B) reaction terminates, dewater, rectifying, obtains containing methyl fluoride or aryl alkyl ketone.
5. the method according to Claims 1-4 any one, is characterized in that: the amount of described NaOR2 be 1.1-2.0 such as formula the mol ratio containing ethyl fluoroacetate shown in A.
6. the method according to Claims 1-4 any one, is characterized in that: the amount of described R2COOH be 0.3 ~ 1.5 such as formula the intermediate mass ratio shown in C.
7. the method according to Claims 1-4 any one, is characterized in that: described H
2sO
4be 15%-50% with the mass concentration of water.
8. the method according to Claims 1-4 any one, is characterized in that: described H
2sO
4be 0.1-0.3 with the mass ratio such as formula the intermediate shown in C.
9. the method according to Claims 1-4 any one, is characterized in that: the amount of described resin cation (R.C.) is 0.1-0.3 with the mass ratio such as formula the intermediate shown in C.
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| CN105001085B (en) * | 2015-04-26 | 2017-03-01 | 衢州学院 | A kind of method that stratified material catalyzes and synthesizes difluoro ethyl acetoacetate |
| 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 |
| CN118063317B (en) * | 2024-04-17 | 2024-06-21 | 江西农业大学 | Preparation method of 4, 4-difluoro acetoacetic acid ethyl ester |
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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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Patent Citations (3)
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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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