CN105777545A - Preparation method of alpha-fluorinated acrylate - Google Patents
Preparation method of alpha-fluorinated acrylate Download PDFInfo
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- CN105777545A CN105777545A CN201610212546.2A CN201610212546A CN105777545A CN 105777545 A CN105777545 A CN 105777545A CN 201610212546 A CN201610212546 A CN 201610212546A CN 105777545 A CN105777545 A CN 105777545A
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- C—CHEMISTRY; METALLURGY
- 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
- C07C67/31—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 functional groups containing oxygen only in singly bound form
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- C—CHEMISTRY; METALLURGY
- 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
- C07C67/317—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
- C07C67/32—Decarboxylation
Abstract
The invention discloses a method for preparing alpha-fluorinated acrylate.The method comprises the steps that raw materials are dissolved into a first organic solvent at first, organic base or inorganic base is added, a hydroxyl protecting agent is added dropwisely on the condition of low temperature ranging from subzero 10 DEG C to 10 DEG C, the temperature is slowly increased to the room temperature to 100 DEG C after dropwise addition is completed, a heat preservation reaction is performed for 3-6 h, water is added for dissolving solids for organic phase washing and liquid separation, an organic phase is concentrated to be dry, the product is added into a second organic solvent, a polymerization inhibitor is added, heating is performed to reach 100-180 DEG C, a reaction is performed for 1-18 h, a mixed solution containing the product is distilled out, and then distillation purification is performed to obtain the alpha-fluorinated acrylate.The method is low in cost, easy to implement and low in equipment requirement, no extremely toxic substance is adopted as raw materials, the whole process is environmentally friendly, the yield is high, the product purity is good, and the method has economic value and is suitable for industrialization.
Description
Technical field
The invention belongs to organic chemical synthesis technical field, particularly relate to the preparation method of a kind of alpha-fluoro acrylic ester.
Background technology
Fiber optic communication has become the important component part of information superhighway the most, and optical fiber includes silica fibre and plastic optical fiber.Pass
The plastic optical fiber of system is polymerized by methyl methacrylate monomer, but owing to it has higher light loss, transmission speed is slow
Shortcoming, therefore the emphasis of research is transferred to fluorine-containing organic compound in the application of plastic optical fiber by people.But, due to α-
The factors such as the batch production of fluoro acrylic ester is high by cost of material, technical difficulty is big are affected, and its industrialization is also in the starting stage.
The method of existing synthesis alpha-fluoro acrylic ester mainly has following several:
A. Claisen condensation method: in organic solvent under sodium hydride basic conditions, is sequentially added into dimethyl oxalate., 2-Fluoroethanoic acid first
Ester, methanol, after backflow, add paraformaldehyde and continue reaction, through post processing, finally give alpha-fluoro acrylic acid methyl ester..Ginseng
Examine document: Li Li etc. ([synthesis chemistry], 2004 (06), 606-7).Raw material alpha-fluoro methyl acetate used by this route is acute
, in industrialized production, there is serious potential safety hazard in drugs.
B. evaporation or de-HCl method: utilize the product 3-chloro-2-fluorine methyl propionate after 3-hydroxyl-2-fluorine methyl propionate or its chlorination
In non-protonic solvent, high temperature dehydration or dehydrochlorination obtain target product.List of references: Japanese Appl.60,78941
And referenced patent: US20120283468.Although the method is simple, but 3-hydroxyl-2-fluorine methyl propionate used is expensive,
And the thionyl chloride used by chlorination is big to equipment corrosion, is not suitable for industrialized great production.
C. dehalogenate method: utilize the bromo-2-of 3-fluoro-2-methyl chloropropionate to obtain target product with zinc powder dehalogenate in acid condition.
List of references: Zh.Org.Khim., 1987,23,1173.The method is raw materials used more difficult prepared, and yield is relatively low.
D. heat resolve method: after carrying out Mannich reaction with 2-fluorine diethyl malonate and aldehyde compound, products therefrom is at high temperature
Under the conditions of crack, directly obtain the mixture of 2-fluoro-3-substitutional crylic acid ethyl ester, then through isolated target product.Reference
Patent: CN103910628.Although the method is simple to operate, but products therefrom purity is the highest, and yield is low, still suffers from deficiency.
Summary of the invention
It is an object of the invention to for the deficiencies in the prior art, it is provided that a kind of method preparing alpha-fluoro acrylic ester.
It is an object of the invention to be achieved through the following technical solutions: the preparation method of a kind of alpha-fluoro acrylic ester, including with
Lower step:
Step 1, by the compound dissolution shown in formula (2) in the first organic solvent, add organic base or inorganic base ,-10～
Under 10 DEG C of reaction temperatures, drip hydroxy protecting agent, drip complete, be to slowly warm up to room temperature～100 DEG C, insulation reaction 3～6
Hour, adding water dissolution solid washing organic facies separatory, concentrating under reduced pressure organic facies, to dry, obtains the compound shown in formula (3)；
Wherein, the consumption of described first organic solvent is 1.5～5 times of the compound quality shown in formula (2), described organic base or nothing
Machine alkali 0.5～2 times that consumption is the compound molal quantity shown in formula (2)；The consumption of described hydroxy protecting agent is formula (2)
1.0～2.0 times of shown compound molal quantity.
Step 2, the compound shown in formula (3) step 1 obtained join in the second organic solvent, add polymerization inhibitor, add
Heat, to 100～180 DEG C of degree, is reacted 1～18h, is distilled out the mixed liquor containing product, then formula (1) institute that rectification and purification obtains
The compound shown；Wherein, the consumption of described second organic solvent is 0.5～5 times of the compound quality shown in formula (3)；Institute
State consumption is the compound by weight shown in formula (3) the 0.01～0.25% of polymerization inhibitor.
Formula (1):
Formula (2):
Formula (3):
In formula, R1Selected from C1～4 alkyl；R2For acyl group.
The invention has the beneficial effects as follows: compared with prior art, low cost of the present invention, simple to operate, low for equipment requirements, not
Using extremely toxic substance as raw material, whole process is environmentally friendly, and yield is high, good product purity, has economic worth, is suitable for
Industrialization.
Accompanying drawing explanation
Fig. 1 is the flow chart of the step 1 of the inventive method；
Fig. 2 is the flow chart of the step 2 of the inventive method.
Detailed description of the invention
The present invention is the preparation method of alpha-fluoro acrylic ester, and the method includes two processes:
Step 1 is as it is shown in figure 1, by the compound dissolution shown in formula (2) in the first organic solvent, add organic base or nothing
Machine alkali, under cryogenic, drips hydroxy protecting agent, drips complete, be warming up to 25～50 DEG C, and insulation reaction 3～6 is little
Time, then it is down to room temperature, add separatory after water dissolution solid, concentrate organic facies the most dry, obtain the compound shown in formula (3).
Step 2, as in figure 2 it is shown, compound step 1 obtained joins in the second organic solvent, adds polymerization inhibitor, adds
Heat, to 100～180 DEG C of degree, is reacted 1～18h, is distilled out the mixed liquor containing product, then rectification and purification obtains highly purified formula (1)
Shown compound.
Formula (1):
Formula (2):
Formula (3):
In formula, R1Selected from C1～4 alkyl, preferably methyl, ethyl.
In formula (3) compound, R2Representative group is acyl group.
In step 1, hydroxy protecting agent used can be acyl chloride compound, specifically, can be C2～12 aliphatic
Acyl chlorides maybe can have the C2 of substituent group～12 aliphatic acyl chlorides, Benzenecarbonyl chloride. maybe can have the Benzenecarbonyl chloride. of substituent group, first sulphur
Acyl chlorides, benzene sulfonyl chloride maybe can have the benzene sulfonyl chloride of substituent group.
Described " can have C2～the 12 aliphatic acyl chlorides of substituent group ", can be the more than one replacement being selected from halogen
The substituted C2 of base～12 aliphatic acyl chlorides.Can be such as chloroacetic chloride, propionyl chloride, butyl chloride, chloracetyl chloride, positive oenanthyl chloro,
Positive caprylyl chloride, trichloro-acetic chloride, 2-bromo propionyl chloro etc..
Described " having the Benzenecarbonyl chloride. of substituent group ", can be selected from halogen, alkyl (preferably C1～4 alkyl) one
The substituted Benzenecarbonyl chloride. of above substituent group.Can be such as parachlorobenzoyl chloride, to fluorobenzoyl chloride, o-chlorobenzoyl chloride,
O-fluoro-benzoyl chloride, m-chlorobenzoyl chloride, a fluorobenzoyl chloride, o-methyl-benzene formyl chloride, to methyl benzoyl chloride, to ethyl
Benzenecarbonyl chloride., cumic aldehyde formyl chloride, 3,5-dichlorobenzoyl chloride, 2-fluoro-4-chlorobenzoyl chloride, 2-chloro-4-fluorobenzoyl
Chlorine, 2,4-dimethyl benzoyl chloride, 2,4 difluorobenzene formyl chloride, phenyl-pentafluoride formyl chloride, pentachlorobenzoyl chloride, 2,3,4,5-tetra-
Fluorobenzoyl chloride etc..
Described " can have the benzene sulfonyl chloride of substituent group ", can be to be selected from halogen, alkyl (preferably C1～4 alkyl)
The substituted benzene sulfonyl chloride of more than one substituent group.Can be such as p-methyl benzene sulfonic chloride, to ethylo benzene sulfonic acid chloride, to isopropyl
Base benzene sulfonyl chloride, parachloroben-zenesulfonyl chloride, to fluorophenylsulfonyl chloride, adjacent fluorophenylsulfonyl chloride, adjacent chlorobenzene sulfonyl chloride, a fluorophenylsulfonyl chloride,
Between chlorobenzene sulfonyl chloride, 2,4 dichloro benzene sulfonic acid chloride, 2,4 difluorobenzene sulfonic acid chloride, 2-chloro-4-fluorophenylsulfonyl chloride, 2,4-diethylbenzene
Sulfonic acid chloride etc..
In this manual, halogen includes fluorine, chlorine, bromine, iodine.
In step 1, hydroxy protecting agent used can also be the compound of anhydrides, can be such as acetic anhydride, propionic andydride,
Butyryl oxide., valeric anhydride, benzoyl oxide, methanesulfonic acid acid anhydride, p-ethylbenzoic acid acid anhydride etc..
In step 1, hydroxy protecting agent used is preferably p-methyl benzene sulfonic chloride, to ethylo benzene sulfonic acid chloride, to methylbenzene first
Acyl chlorides, p-ethylbenzoyl chloride, Benzenecarbonyl chloride., acetic anhydride, propionic andydride, n butanoic anhydride.
In step 1, the consumption of described hydroxy protecting agent is 1.0～2.0 times of the compound molal quantity shown in formula (2),
It is preferably 1.0～1.5 times.
In step 1, the first described organic solvent is non-protonic solvent, such as, can enumerate normal hexane, hexamethylene, positive heptan
Alkane, isoheptane, 1,1-dichloroethanes, 1,2-dichloroethanes, dichloromethane, chloroform, carbon tetrachloride, benzene, toluene,
Dimethylbenzene, methyl formate, Ethyl formate, ethyl acetate, ethyl propionate, ethyl n-butyrate. etc., the most preferably normal hexane, ring
Hexane, toluene, 1,2-dichloroethanes, dichloromethane, methyl acetate, ethyl acetate.The first selected organic solvent is permissible
It is used alone, it is also possible to two or more be applied in combination by any proportioning.
In step 1, the consumption of the first described organic solvent is 1.5～5.0 times of the quality of the compound shown in formula (2),
It is preferably 2.0～3.0 times.
In step 1, described organic base can be triethylamine, pyridine, DBU, DBN, DMAP, N-methylmorpholine, tetramethyl second
Diamidogen, N, accelerine, N-methyl piperidine, imidazoles, piperidines, N, N-dimethylaminopyridine etc.；Described inorganic base
Can be sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate etc..Selected alkali can be independent
Use or be applied in combination.
In step 1, described organic base or the consumption of inorganic base are the 0.5～2.0 of the molal quantity of the compound shown in formula (2)
Times, preferably 0.6～1.5 times.
In step 1, described dropping temperature is-10～10 DEG C.
In step 1, described insulation reaction temperature is room temperature～100 DEG C, preferably room temperature～50 DEG C.
In step 2, described second organic solvent is non-proton organic solvent.Such as can enumerate dimethyl sulfoxide, N, N-bis-
Methylformamide, DMAC N,N' dimethyl acetamide, ethylene glycol, ethylene glycol derivative (such as glycol monoethyl ether, diethylene glycol two
Methyl ether, diethylene glycol diethyl ether, TRIGLYME, four diethanol dimethyl ether etc.), quinoline, tetrahydroquinoline, N-methyl pyrrole
Pyrrolidone, sulfolane, 1,3-dimethyl-imidazolinone, hexamethyl phosphoramide, dimethylbenzene, sym-trimethylbenzene., alkanes are (such as
Decane, dodecane) etc..Be preferably dimethyl sulfoxide, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, ethylene glycol,
Diethylene glycol dimethyl ether, sulfolane, N-Methyl pyrrolidone, 1,3-dimethyl-imidazolinone.Second organic solvent can be independent
Use one, it is also possible to two or more be used in mixed way by any proportioning.
In step 2, described second organic solvent preferably have more than 100 DEG C boiling points, more preferably have more than 120 DEG C boiling point,
Further preferably there is the organic solvent of the boiling point of more than 150 DEG C.The boiling point upper limit does not set, usually 300 DEG C.
In step 2, the consumption of described second organic solvent, relative to the quality of the compound shown in above-mentioned formula (3), generally exist
0.5～5 times, preferably 1.0～2.5 times.
In step 2, can add polymerization inhibitor in described second organic solvent, polymerization inhibitor is conventional polymerization inhibitor, such as 2,6-bis-uncle
Butyl-4-methylphenol (BHT), 4-methoxyphenol, hydroquinone, phenothiazine, benzoquinone etc..Polymerization inhibitor can be therein
A kind of, it is also possible to for more than two of which pressing the combination of any proportioning.
In step 2, the amount of this polymerization inhibitor, relative to the weight of the compound shown in above-mentioned formula (3), generally 0.01～0.25%
In weight ratio, preferably 0.03～0.10%.
In step 2, reaction temperature is 100～180 DEG C, preferably 140～170 DEG C.
In step 2, the response time is set as that yield reaches the maximum time, specifically, generally 1～18h, uses
Higher reaction temperature, can shorten the response time further.
In step 2, the generating mode of the compound shown in described formula (1) is: had by the compound and second shown in formula (3)
Machine solvent joins in reactor, is heated to reaction temperature, reacts certain time, then steams from reaction system.
Compound shown in Chinese style of the present invention (2) can be by the method selection corresponding 2-fluoro described in patent CN86103531
Diester malonate and formaldehyde prepare.
Describing the present invention in detail below according to embodiment, the purpose of the present invention and effect will be apparent from, wherein, and embodiment
1-embodiment 8 is the specific embodiment of the step 1 of the inventive method, and embodiment 9-embodiment 16 is the step 2 of the inventive method
Specific embodiment.
Embodiment 1
By 208.2g formula (2) compound [R1=Et], 313 gram 1,2-dichloroethanes, 107g triethylamine join in reactor,
It is cooled to 0 DEG C, instills 107g acetic anhydride in 2h, drip complete, be slowly increased to 80 DEG C, insulation reaction 3h, then it is cooled to room
Temperature, adds separatory after 200g water dissolution solid, organic facies negative pressure desolvation, obtains 242.7g formula (3) compound [R1=Et,
R2=AcO], yield 97%.
Embodiment 2
By 236.3g formula (2) compound [R1=n-Pr], 1063 grams of chloroforms, 58.3g sodium carbonate join in reactor, cooling
To 3 DEG C, instill 209.7g paratoluensulfonyl chloride in 3h, drip complete, be slowly warmed up to 35 DEG C, insulation reaction 4.5h, then
It is cooled to room temperature, adds separatory after 280g water dissolution solid, organic facies negative pressure desolvation, obtain 349.4g formula (3) chemical combination
Thing [R1=n-Pr, R2=TsO], yield 89.6%.
Embodiment 3
By 180.1g formula (2) compound [R1=Me], 540 grams of normal hexane, 151.2g sodium bicarbonate join in reactor, fall
Temperature, to 5 DEG C, instills 278.3g in 3.5h to methyl benzoyl chloride, drips complete, is slowly increased to room temperature, insulation reaction 6h,
Add separatory after 350g water dissolution solid, organic facies negative pressure desolvation, obtain 269.3g formula (3) compound [R1=Me, R2=
To methyl benzoyl], yield 90.3%.
Embodiment 4
By 208.2g formula (2) compound [R1=Et], 520 grams of dichloromethane, 121.5g triethylamines join in reactor, fall
Temperature, to-5 DEG C, instills 154.5g Benzenecarbonyl chloride., drips complete, be to slowly warm up to 35 DEG C in 1.5h, insulation reaction 5h, then drops
To room temperature, add separatory after 200g water dissolution solid, organic facies negative pressure desolvation, obtain 300.7g formula (3) compound [R1=Et,
R2=benzoyl], yield 96.3%.
Embodiment 5
By 180.1g formula (2) compound [R1=Me], 630 grams of toluene, 42.4g sodium hydroxide join in reactor, cooling
To-10 DEG C, instill 183.8g parachlorobenzoyl chloride in 2h, drip complete, be to slowly warm up to 95 DEG C, insulation reaction 3.5h,
It is down to room temperature again, adds separatory after 250g water dissolution solid, organic facies negative pressure desolvation, obtain 265.5g formula (3) chemical combination
Thing [R1=Me, R2=to chlorobenzene formacyl], yield 83.3%.
Embodiment 6
By 180.1g formula (2) compound [R1=Me], 360 grams of dichloromethane, 161.9g triethylamines join in reactor, fall
Temperature, to 0 DEG C, instills 210.8g Benzenecarbonyl chloride., drips complete, be to slowly warm up to 50 DEG C in 2h, insulation reaction 4h, then is down to
Room temperature, adds separatory after 200g water dissolution solid, organic facies negative pressure desolvation, obtains 272.5g formula (3) compound [R1=Me,
R2=benzoyl], yield 95.9%.
Embodiment 7
By 180.1g formula (2) compound [R1=Me], 998 grams of ethyl acetate, 158.8gDMAP join in reactor, cooling
To-5 DEG C, instill 122.5g acetic anhydride in 1.5h, drip complete, be slowly increased to 45 DEG C, insulation reaction 5h, then it is down to room temperature,
Add separatory after 300g water dissolution solid, organic facies negative pressure desolvation, obtain 205.8g formula (3) compound [R1=Me,
R2=acetyl group], yield 92.6%.
Embodiment 8
By 180.1g formula (2) compound [R1=Me], 720 grams of benzene, 146.3g pyridines join in reactor, be cooled to 8 DEG C,
Instill the positive caprylyl chloride of 244.0g in 3h, drip complete, be to slowly warm up to 35 DEG C, insulation reaction 6h, then it is down to room temperature, add
Separatory after 350g water dissolution solid, organic facies negative pressure desolvation, obtain 165.5g formula (3) compound [R1=Me, R2=the most pungent
Acyl group], yield 86.7%.
Embodiment 9
By 165gNMP, 240mg phenothiazine, 250.2g formula (3) compound [R1=Et, R2=Ac] join in reactor, it is heated to
180 DEG C, reacting 7h, distillation obtains mixed liquor, and this mixed liquor, after rectification, obtains 101.5g alpha-fluoro ethyl acrylate,
Product through IR,1H-NMR、13C-NMR analyzes, for alpha-fluoro ethyl acrylate, content: 99.1%, yield: 85.9%.
Embodiment 10
By 200gN, N-dimethyl acetylamide, 100mg hydroquinone, by 312.1g formula (3) compound [R1=Et, R2=to chlorobenzene first
Acyl group] join in reactor, be heated to 160 DEG C, react about 13h, distillation obtains mixed liquor, mixing liquid after rectification,
Obtain 105.9g alpha-fluoro ethyl acrylate, product through IR,1H-NMR、13C-NMR analyzes, and for alpha-fluoro ethyl acrylate, contains
Amount: 99.4%, yield: 79.8%.
Embodiment 11
By 598g sulfolane, 240mg phenothiazine, 213.3g formula (3) compound [R1=Me, R2=benzoyl] join reactor
In, it being heated to 180 DEG C, react about 6h, distillation obtains mixed liquor, and this mixed liquor, after rectification, obtains 65.6g alpha-fluoro third
E pioic acid methyl ester, product through IR,1H-NMR、13C-NMR analyzes, for alpha-fluoro acrylic acid methyl ester., and content: 99.2%, yield:
83.9%.
Embodiment 12
By 450g1,3-dimethyl-imidazolinone, 420mg4-methoxyphenol, 253.5g formula (3) compound [R1=Me, R2=to first
Base benzoyl] join in reactor, it is heated to 170 DEG C, reacts 9h, distillation obtains mixture, and this mixture is through rectification
After, obtain 71.9g alpha-fluoro acrylic acid methyl ester., product through IR,1H-NMR、13C-NMR analyzes, for alpha-fluoro acrylic acid methyl ester.,
Content: 99.5%, yield: 81.2%.
Embodiment 13
By 470g dimethyl sulfoxide, 80mgBHT, 200.4g formula (3) compound [R1=Et, R2=CH3SO2] join in reactor, add
Heat, to 160 DEG C, reacts 11h, and distillation obtains mixture, and this mixture, after rectification, obtains 64.3g alpha-fluoro acrylic acid second
Ester, product through IR,1H-NMR、13C-NMR analyzes, for alpha-fluoro ethyl acrylate, content: 99.2%, yield: 77.8%.
Embodiment 14
By 468g sulfolane, 30mgBHT, 234.1g formula (3) compound [R1=Me, R2=Ts] join in reactor, it is heated to
140 DEG C, reacting about 17h, distillation obtains mixed liquor, and mixed liquor, after rectification, obtains 53.7g alpha-fluoro acrylic acid methyl ester.,
Product through IR,1H-NMR、13C-NMR analyzes, for alpha-fluoro acrylic acid methyl ester., content: 99.5%, yield: 73.8%.
Embodiment 15
By 313gNMP, 360mg hydroquinone, 312.3g formula (3) compound [R1=Et, R2=benzoyl] join in reactor,
Being heated to 165 DEG C, react about 10h, distillation obtains mixed liquor, and this mixed liquor, after rectification, obtains 98.8g alpha-fluoro propylene
Acetoacetic ester, product through IR,1H-NMR、13C-NMR analyzes, for alpha-fluoro ethyl acrylate, content: 99.6%, yield: 83.6%.
Embodiment 16
By 760g1,3-dimethyl-imidazolinone, 480mg phenothiazine, 190g formula (3) compound [R1=Me, R2=n-octyl] add
In reactor, being heated to 170 DEG C, react about 15h, distillation obtains mixed liquor, this mixed liquor after rectification, obtain 54.9g α-
Fluoromethacrylate, product through IR,1H-NMR、13C-NMR analyzes, for alpha-fluoro acrylic acid methyl ester., and content: 99.4%,
Yield: 81.2%.
According to the present invention, obtain the mixture of more segregative two kinds of materials, obtain high receipts with low cost, low energy consumption, low stain
Rate, highly purified 2-fluoro acrylic ester.
It should be understood that embodiments of the invention are merely to the non-limiting invention that is more fully understood that the present invention and makes the present invention.
The present invention can be made various amendment in without departing from the spirit and scope of the present invention, replace and change by those skilled in the art,
These amendments, replace and change still falls within protection scope of the present invention.
Claims (10)
1. the preparation method of an alpha-fluoro acrylic ester, it is characterised in that comprise the following steps:
Step 1, by the compound dissolution shown in formula (2) in the first organic solvent, add organic base or inorganic base ,-10～
Under 10 DEG C of cryogenic conditions, drip hydroxy protecting agent, drip complete, be to slowly warm up to room temperature～100 DEG C, insulation reaction 3～6
Hour, add water dissolution solid, washing organic facies separatory, concentrate organic facies the most dry, obtain the compound shown in formula (3)；
Wherein, the consumption of described first organic solvent is 1.5～5 times of the compound quality shown in formula (2), described organic base or nothing
Machine alkali 0.5～2 times that consumption is the compound molal quantity shown in formula (2)；The consumption of described hydroxy protecting agent is formula (2)
1.0～2.0 times of shown compound molal quantity.
Step 2, the compound shown in formula (3) step 1 obtained join in the second organic solvent, add polymerization inhibitor, add
Heat, to 100～180 DEG C of degree, reacts 1～18h, distills out the mixed liquor containing product, then rectification and purification obtains shown in formula (1)
Compound；Wherein, the consumption of described second organic solvent is 0.5～5 times of the compound quality shown in formula (3)；Described
The consumption of polymerization inhibitor is 0.01～0.25% of the compound by weight shown in formula (3)；
Formula (1):
Formula (2):
Formula (3):
In formula, R1Selected from C1～4 alkyl；R2For acyl group.
Method the most according to claim 1, it is characterised in that in described step 1, described hydroxy protecting agent can be
Acyl chloride compound, it is also possible to be the compound of anhydrides.
Method the most according to claim 2, it is characterised in that described acyl chloride compound is selected from C2～12 aliphatic acyls
Chlorine maybe can have the C2 of substituent group～12 aliphatic acyl chlorides, Benzenecarbonyl chloride. maybe can have the Benzenecarbonyl chloride. of substituent group, first sulphur
Acyl chlorides, benzene sulfonyl chloride maybe can have the benzene sulfonyl chloride of substituent group.
Method the most according to claim 2, it is characterised in that the compound of described anhydrides selected from acetic anhydride, propionic andydride,
Butyryl oxide., valeric anhydride, benzoyl oxide, methanesulfonic acid acid anhydride, p-ethylbenzoic acid acid anhydride etc..
Method the most according to claim 1, it is characterised in that in described step 1, described hydroxy protecting agent is preferably
P-methyl benzene sulfonic chloride, to ethylo benzene sulfonic acid chloride, to methyl benzoyl chloride, p-ethylbenzoyl chloride, Benzenecarbonyl chloride., acetic anhydride,
Propionic andydride, n butanoic anhydride.
Method the most according to claim 1, it is characterised in that in described step 1, the use of described hydroxy protecting agent
Amount is preferably 1.0～1.5 times of the compound molal quantity shown in formula (2)；The consumption of described first organic solvent is preferably formula (2)
2.0～3.0 times of shown compound quality；Described organic base or the consumption of inorganic base are preferably the compound shown in formula (2)
0.6～1.5 times of molal quantity；In described step (2), the consumption of described second organic solvent is preferably shown in formula (3)
1.0～2.5 times of compound quality；The consumption of described polymerization inhibitor is preferably 0.03～0.1% of the compound by weight shown in formula (3).
Method the most according to claim 1, it is characterised in that in described step 1, the first described organic solvent is non-
Protonic solvent, selected from normal hexane, hexamethylene, normal heptane, isoheptane, 1,1-dichloroethanes, 1,2-dichloroethanes, dichloromethane
Alkane, chloroform, carbon tetrachloride, benzene, toluene, dimethylbenzene, methyl formate, Ethyl formate, ethyl acetate, ethyl propionate,
Ethyl n-butyrate.；It is preferably normal hexane, hexamethylene, toluene, 1,2-dichloroethanes, dichloromethane, ethyl acetate.
Method the most according to claim 1, it is characterised in that in described step 1, described organic base can be triethylamine,
Pyridine, DBU, DBN, DMAP, N-methylmorpholine, tetramethylethylenediamine, DMA, N-methyl piperidine,
Imidazoles, piperidines, N, N-dimethylaminopyridine etc..
Method the most according to claim 1, it is characterised in that in described step 1, described inorganic base can be hydroxide
Sodium, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate etc..
Method the most according to claim 1, it is characterised in that in described step 2, described second organic solvent is non-
Protic organic solvent, selected from dimethyl sulfoxide, DMF, N,N-dimethylacetamide, ethylene glycol, second two
01 derivatives, quinoline, tetrahydroquinoline, N-Methyl pyrrolidone, sulfolane, 1,3-dimethyl-imidazolinone, hexamethyl phosphoramide,
Dimethylbenzene, sym-trimethylbenzene., decane, dodecane；It is preferably dimethyl sulfoxide, N,N-dimethylformamide, N, N-dimethyl second
Amide, ethylene glycol, diethylene glycol dimethyl ether, sulfolane, N-Methyl pyrrolidone, 1,3-dimethyl-imidazolinone.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108707115A (en) * | 2018-07-17 | 2018-10-26 | 成都道合尔医药技术有限公司 | A kind of synthetic method of acrylic acid derivative |
| WO2021215452A1 (en) * | 2020-04-20 | 2021-10-28 | ダイキン工業株式会社 | METHOD FOR PRODUCING α-FLUOROACRYLIC ACID ESTER |
| WO2021215450A1 (en) * | 2020-04-20 | 2021-10-28 | ダイキン工業株式会社 | METHOD FOR PRODUCING α-FLUOROACRYLIC ACID ESTER |
| CN115894197A (en) * | 2022-12-06 | 2023-04-04 | 湖南久日新材料有限公司 | Alkaline hydrolysis method for preparing alpha-hydroxyisobutyrophenone |
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| CN102211999A (en) * | 2011-05-25 | 2011-10-12 | 原平市同利化工有限责任公司 | Method for preparing 2-fluoroalkyl acrylate |
| CN103910628A (en) * | 2012-12-28 | 2014-07-09 | 大金工业株式会社 | Method For Manufacturing Alpha-fluoroacrylates |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102211999A (en) * | 2011-05-25 | 2011-10-12 | 原平市同利化工有限责任公司 | Method for preparing 2-fluoroalkyl acrylate |
| CN103910628A (en) * | 2012-12-28 | 2014-07-09 | 大金工业株式会社 | Method For Manufacturing Alpha-fluoroacrylates |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108707115A (en) * | 2018-07-17 | 2018-10-26 | 成都道合尔医药技术有限公司 | A kind of synthetic method of acrylic acid derivative |
| WO2021215452A1 (en) * | 2020-04-20 | 2021-10-28 | ダイキン工業株式会社 | METHOD FOR PRODUCING α-FLUOROACRYLIC ACID ESTER |
| WO2021215450A1 (en) * | 2020-04-20 | 2021-10-28 | ダイキン工業株式会社 | METHOD FOR PRODUCING α-FLUOROACRYLIC ACID ESTER |
| JP2021172661A (en) * | 2020-04-20 | 2021-11-01 | ダイキン工業株式会社 | Method for producing α-fluoroacrylic acid ester |
| JP2021172662A (en) * | 2020-04-20 | 2021-11-01 | ダイキン工業株式会社 | Method for producing α-fluoroacrylic acid ester |
| CN115443262A (en) * | 2020-04-20 | 2022-12-06 | 大金工业株式会社 | Method for producing alpha-fluoroacrylate |
| CN115894197A (en) * | 2022-12-06 | 2023-04-04 | 湖南久日新材料有限公司 | Alkaline hydrolysis method for preparing alpha-hydroxyisobutyrophenone |
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