CN117510330A - Preparation method of low-cost and high-efficiency 2, 2-ethyl difluoroacetate - Google Patents
Preparation method of low-cost and high-efficiency 2, 2-ethyl difluoroacetate Download PDFInfo
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- GZKHDVAKKLTJPO-UHFFFAOYSA-N ethyl 2,2-difluoroacetate Chemical compound CCOC(=O)C(F)F GZKHDVAKKLTJPO-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 65
- 239000011259 mixed solution Substances 0.000 claims abstract description 56
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000012346 acetyl chloride Substances 0.000 claims abstract description 28
- 239000012074 organic phase Substances 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 14
- 238000010791 quenching Methods 0.000 claims abstract description 14
- 230000000171 quenching effect Effects 0.000 claims abstract description 14
- VUYQBMXVCZBVHP-UHFFFAOYSA-N 1,1-difluoroethanol Chemical compound CC(O)(F)F VUYQBMXVCZBVHP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000007864 aqueous solution Substances 0.000 claims abstract description 13
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 13
- 238000005406 washing Methods 0.000 claims abstract description 13
- 239000011261 inert gas Substances 0.000 claims abstract description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- 238000000605 extraction Methods 0.000 claims description 6
- 239000011736 potassium bicarbonate Substances 0.000 claims description 5
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 5
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 235000011181 potassium carbonates Nutrition 0.000 claims description 5
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 235000017550 sodium carbonate Nutrition 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 11
- 230000008901 benefit Effects 0.000 abstract description 6
- 239000002699 waste material Substances 0.000 abstract description 4
- 239000000047 product Substances 0.000 description 45
- 239000000243 solution Substances 0.000 description 9
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000004817 gas chromatography Methods 0.000 description 4
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- BEPCUGVFWAYLBF-UHFFFAOYSA-N 1,1,1,2-tetrafluoro-2-methoxyethane Chemical compound COC(F)C(F)(F)F BEPCUGVFWAYLBF-UHFFFAOYSA-N 0.000 description 2
- CRLSHTZUJTXOEL-UHFFFAOYSA-N 2,2-difluoroacetyl fluoride Chemical compound FC(F)C(F)=O CRLSHTZUJTXOEL-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- -1 halogenated difluoro acetate alkane Chemical class 0.000 description 2
- KRJKJVSLOIGMGA-UHFFFAOYSA-N n,n-diethyl-2,2-difluoroacetamide Chemical compound CCN(CC)C(=O)C(F)F KRJKJVSLOIGMGA-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- QZFIQARJCSJGEG-UHFFFAOYSA-N 1,1,1,2-tetrafluoro-2-(1,2,2,2-tetrafluoroethoxy)ethane Chemical compound FC(F)(F)C(F)OC(F)C(F)(F)F QZFIQARJCSJGEG-UHFFFAOYSA-N 0.000 description 1
- PFJLHSIZFYNAHH-UHFFFAOYSA-N 2,2-difluoroethyl acetate Chemical compound CC(=O)OCC(F)F PFJLHSIZFYNAHH-UHFFFAOYSA-N 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007233 catalytic pyrolysis Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- PBWZKZYHONABLN-UHFFFAOYSA-N difluoroacetic acid Chemical compound OC(=O)C(F)F PBWZKZYHONABLN-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/14—Preparation of carboxylic acid esters from carboxylic acid halides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C67/54—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/58—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E60/00—Enabling technologies; Technologies with a potential or indirect contribution to GHG emissions mitigation
- Y02E60/10—Energy storage using batteries
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of low-cost and high-efficiency ethyl 2, 2-difluoroacetate, which comprises the steps of adding difluoroethanol into a reaction container under the protection of inert gas, slowly dropwise adding acetyl chloride under the low-temperature condition, continuously reacting for 0.5-2 h in the reaction container after the acetyl chloride is dropwise added to obtain a mixed solution A, adding a saturated alkaline aqueous solution into the mixed solution A for quenching reaction, washing an organic phase to obtain a mixed solution B, extracting and separating the mixed solution B, collecting the organic phase, and performing pressure rectification in a reaction kettle for 3 hours to obtain a finished product of the ethyl 2, 2-difluoroacetate. The 2, 2-ethyl difluoroacetate prepared by the method has the advantages of higher product purity, simple preparation process, mild reaction process, lower production cost, low equipment requirement, simple treatment of three wastes after the production of the product, suitability for large-scale popularization and production and high economic benefit, and a producer can select different saturated alkaline aqueous solutions according to own input budget.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of low-cost and high-efficiency 2, 2-ethyl difluoroacetate.
Background
The 2, 2-ethyl difluoroacetate is an intermediate product of a plurality of downstream drug synthesis and functional materials, is also an important raw material for synthesizing 5-fluorouracil, fluorocytosine, difluoroalcohol and halogenated difluoro acetate alkane, and is also a catalyst for cyclization and oxidation.
In the prior art, tetrafluoroethylene and absolute ethyl alcohol are generally used as raw materials to synthesize tetrafluoroethyl ethyl ether, and then the tetrafluoroethyl ether and water are catalyzed by concentrated acid to synthesize ethyl difluoroacetate; under the catalysis of a catalyst, adding tetrafluoroethylene and methanol to synthesize methoxy tetrafluoroethane, performing catalytic pyrolysis on the methoxy tetrafluoroethane to obtain difluoro acetyl fluoride, and esterifying the difluoro acetyl fluoride with ethanol to obtain difluoro ethyl acetate; tetrafluoroethylene, diethylamine and water react in an autoclave to obtain N, N-diethyl difluoroacetamide, the N, N-diethyl difluoroacetamide is hydrolyzed to obtain difluoroacetic acid, and the target product is obtained through esterification. The method has some defects, such as difficult acquisition of tetrafluoroethylene, high equipment requirement, high risk in the production process, and large three wastes, and is not beneficial to large-scale production.
In order to solve the problems, the invention provides a preparation method of low-cost and high-efficiency 2, 2-ethyl difluoroacetate.
Disclosure of Invention
In order to solve the technical problems, the invention provides a preparation method of low-cost and high-efficiency 2, 2-ethyl difluoroacetate, which is characterized by comprising the following steps:
s1, under the protection of inert gas, difluoroethanol is added into a reaction container, acetyl chloride is slowly added dropwise under the low-temperature condition, and after the acetyl chloride is added dropwise, the reaction is continued in the reaction container for 0.5-2 h, so as to obtain a mixed solution A;
s2, based on S1, adding a saturated alkaline aqueous solution into the mixed solution A for quenching reaction, and then washing an organic phase to obtain a mixed solution B;
s3, based on S2, extracting and separating the mixed solution B, collecting an organic phase, and performing pressure rectification in a reaction kettle for 3 hours to obtain a finished product of the 2, 2-ethyl difluoroacetate.
Preferably, in the step S1, the molar ratio of difluoroethanol to acetyl chloride in the reaction vessel is 1:1-2, and acetyl chloride is dropwise added at the temperature of 0-20 ℃;
preferably, in the step S1, the reaction temperature after the completion of the addition of acetyl chloride is 30 to 60 ℃.
Preferably, in the step S2, the base of the saturated alkaline aqueous solution for quenching reaction is one of sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate.
Preferably, in the step S2, the alkali of the saturated alkaline aqueous solution for washing the organic phase is one of sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate.
Preferably, in the step S3, the temperature of the reaction kettle is controlled within 100-150 ℃, and the distillate extraction ratio after rectification is 1: the temperature of the finished product of the ethyl 2, 2-difluoroacetate is 76-79 ℃ in the ratio of 40-10:40.
The chemical reaction equations mainly involved in this embodiment are:
compared with the prior art, the invention has the following beneficial effects:
(1) According to the invention, difluoroethanol is added into a reaction container under the protection of inert gas, acetyl chloride is slowly added dropwise under the low-temperature condition, the reaction is continued for 0.5-2 h in the reaction container after the acetyl chloride is added dropwise, a mixed solution A is obtained, a saturated alkaline aqueous solution is added into the mixed solution A for quenching reaction, an organic phase is washed, a mixed solution B is obtained, the mixed solution B is extracted and separated, an organic phase is collected, and the finished product of 2, 2-ethyl difluoroacetate is obtained after 3 hours of pressure rectification in a reaction kettle. The 2, 2-ethyl difluoroacetate prepared by the method has the advantages of higher product purity, simple preparation process, mild reaction process, lower production cost, low equipment requirement, simple treatment of three wastes after the production of the product, suitability for large-scale popularization and production and high economic benefit, and a producer can select different saturated alkaline aqueous solutions according to own input budget.
Drawings
FIG. 1 is a gas chromatogram of a mixed solution B in example 2 of the present invention.
FIG. 2 is a gas chromatogram of mixed solution B in example 3 of the present invention.
FIG. 3 is a gas chromatogram of mixed solution B in example 4 of the present invention.
FIG. 4 is a gas chromatogram of mixed solution B in example 5 of the present invention.
FIG. 5 is a gas chromatogram of mixed solution B in example 6 of the present invention.
Detailed Description
The invention will be further described with reference to the drawings and detailed description.
In the description of the present invention, unless otherwise indicated, the meaning of "a plurality" is two or more; the terms "upper," "lower," "left," "right," "inner," "outer," "front," "rear," "head," "tail," and the like are used as an orientation or positional relationship based on that shown in the drawings, merely to facilitate description of the invention and to simplify the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore should not be construed as limiting the invention. Furthermore, the terms "first," "second," "third," and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
In the description of the present invention, it should be noted that, unless explicitly specified and limited otherwise, the terms "connected," "connected," and "connected" are to be construed broadly, and may be either fixedly connected, detachably connected, or integrally connected, for example; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art.
Example 1
S1, under the protection of inert gas, adding difluoroethanol into a reaction container, slowly dropwise adding acetyl chloride under the low-temperature condition, wherein the reaction mole ratio of difluoroethanol to acetyl chloride in the reaction container is 1:1-2, dropwise adding acetyl chloride under the temperature condition of 0-20 ℃, and continuously reacting in the reaction container for 0.5-2 h after the acetyl chloride is dropwise added, wherein the reaction temperature is 30-60 ℃, so as to obtain a mixed solution A;
s2, based on S1, adding a saturated alkaline aqueous solution into the mixed solution A for quenching reaction, and then washing an organic phase to obtain a mixed solution B, wherein specifically, the alkali of the saturated alkaline aqueous solution for quenching reaction and washing the organic phase is one of sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate;
s3, based on S2, extracting and separating the mixed solution B, collecting an organic phase, controlling the temperature of a reaction kettle within 100-150 ℃, and controlling the extraction ratio of the distilled fraction to be 1: 40-10:40, the extraction content of the 2, 2-ethyl difluoroacetate product in the fraction is 99.1-99.35%, the purity of the finished product of the 2, 2-ethyl difluoroacetate is 99.5-99.85% after 3 hours of pressure rectification in a reaction kettle, and the temperature of the finished product of the 2, 2-ethyl difluoroacetate is 76-79 ℃.
Example 2
S1, under the protection of inert gas, 50g of difluoroethanol is added into a reaction container, 52.5g of acetyl chloride is slowly added dropwise from 3 ℃, the reaction temperature is controlled within 10 ℃, the acetyl chloride is heated to 30 ℃ after being added dropwise, the reaction is continued in the reaction container for 1h, and a mixed solution A is obtained, and the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution A in the embodiment is 94.2%;
s2, based on S1, adding saturated sodium carbonate solution into the mixed solution A for quenching reaction, and then washing an organic phase to obtain a mixed solution B;
s3, extracting and separating the mixed solution B based on S2, and collecting an organic phase, wherein the purity of the 2, 2-ethyl difluoroacetate product in the mixed solution B in the embodiment is 99.45%, the weight of the recovered 2, 2-ethyl difluoroacetate product after liquid separation is 68.29g, and the product yield of the 2, 2-ethyl difluoroacetate is 90.3%. As shown in fig. 1, the gas chromatographic analysis results of the mixed solution B are shown in the following table:
analysis results table
Example 3
S1, under the protection of inert gas, 50g of difluoroethanol is added into a reaction container, 52.5g of acetyl chloride is slowly added dropwise from 18 ℃, the temperature is raised to 37 ℃ at the highest, and after the acetyl chloride is added dropwise, the reaction is continued in the reaction container for 0.5h, so that a mixed solution A is obtained, and the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution A in the embodiment is 97.5%;
s2, based on S1, adding saturated sodium carbonate solution into the mixed solution A for quenching reaction, and then washing an organic phase to obtain a mixed solution B;
s3, based on S2, extracting and separating the mixed solution B, and collecting an organic phase, wherein the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution B of the embodiment is 99.46%, the weight of the recovered 2, 2-ethyl difluoroacetate product after liquid separation is 69.12g, and the product yield of the 2, 2-ethyl difluoroacetate is 91.4%. As shown in fig. 2, the results of the gas chromatography are shown in the following table:
analysis results table
Example 4
S1, under the protection of inert gas, adding 200g of difluoroethanol into a reaction container, slowly dropwise adding 211g of acetyl chloride at 20 ℃, heating to 32 ℃ at the highest, and continuously reacting in the reaction container for 45min after the acetyl chloride is dropwise added to obtain a mixed solution A, wherein the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution A in the embodiment is 96.5%;
s2, based on S1, adding saturated sodium carbonate solution into the mixed solution A for quenching reaction, washing an organic phase to obtain a mixed solution B,
s3, extracting and separating the mixed solution B based on S2, and collecting an organic phase, wherein the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution B in the embodiment is 99.46%, the weight of the recovered 2, 2-ethyl difluoroacetate product after liquid separation is 272.2g, and the product yield of the 2, 2-ethyl difluoroacetate is 89.9%. As shown in fig. 3, the results of the gas chromatography are shown in the following table:
analysis results table
The ethyl 2, 2-difluoroacetate products recovered in example 2, example 3 and example 4 were collected and subjected to normal pressure rectification in step S3, and the product content before distillation is shown in the following table:
| time (minutes) | 1.9 (difluoro) | 2.1 (acid chloride) | 2.7 (unknown) | 3.2 (product) |
| Content (%) | 0.37 | 0.16 | 0.01 | 99.46 |
Controlling the temperature in the reaction kettle to be 108-112 ℃, and distilling for 3 hours, wherein the fraction extraction ratio is 5:40, the product temperature is between 76 and 79 ℃, and the content of the extracted fraction is shown in the following table:
| time (minutes) | 1.9 (difluoro) | 2.1 (acid chloride) | 2.7 (unknown) | 3.2 (product) |
| Content (%) | 0.66 | / | / | 99.34 |
The contents of the products in the reaction kettle are shown in the following table:
| time (minutes) | 1.9 (difluoro) | 2.1 (acid chloride) | 2.7 (unknown) | 3.2 (product) |
| Content (%) | 0.39 | / | / | 99.61 |
Example 5
S1, under the protection of inert gas, 50g of difluoroethanol is added into a reaction container, 55g of acetyl chloride is slowly added dropwise from 20 ℃, the temperature is raised to 40 ℃ at the highest, the temperature is kept, the reaction is continued for 1.75 hours in the reaction container after the acetyl chloride is added dropwise, and a mixed solution A is obtained, wherein the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution A in the embodiment is 98.7%;
s2, based on S1, adding saturated sodium bicarbonate solution into the mixed solution A for quenching reaction, and then washing an organic phase to obtain a mixed solution B;
s3, extracting and separating the mixed solution B based on S2, and collecting an organic phase, wherein specifically, the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution B in the embodiment is 99.89%, the weight of the recovered 2, 2-ethyl difluoroacetate product after liquid separation is 64.63g, and the product yield of the 2, 2-ethyl difluoroacetate is 85.5%. As shown in fig. 4, the results of the gas chromatography are shown in the following table:
analysis results table
Example 6
S1, under the protection of inert gas, 50g of difluoroethanol is added into a reaction container, 55g of acetyl chloride is slowly added dropwise from 1 ℃, the reaction temperature is controlled within 10 ℃, the acetyl chloride is heated to 30 ℃ after being added dropwise, the reaction is continued for 50min in the reaction container, and a mixed solution A is obtained, and the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution A in the embodiment is 97.3%;
s2, based on S1, adding saturated sodium bicarbonate solution into the mixed solution A for quenching reaction, and then washing an organic phase to obtain a mixed solution B;
s3, extracting and separating the mixed solution B based on S2, and collecting an organic phase, wherein specifically, the product purity of the 2, 2-ethyl difluoroacetate in the mixed solution B in the embodiment is 99.8%, the weight of the recovered 2, 2-ethyl difluoroacetate product after liquid separation is 61.8g, and the product yield of the 2, 2-ethyl difluoroacetate is 82%. As shown in fig. 5, the results of the gas chromatography are shown in the following table:
analysis results table
The ethyl 2, 2-difluoroacetate products recovered in example 5 and example 6 were collected and subjected to normal pressure rectification in step S3, and the product content before distillation was as shown in the following table:
| time (minutes) | 1.9 (difluoro) | 2.1 (acid chloride) | 2.7 (unknown) | 3.2 (product) |
| Content (%) | 0.05 | 0.08 | 0.02 | 99.85 |
Controlling the temperature in the reaction kettle to be 110-120 ℃, and distilling for 3 hours, wherein the fraction extraction ratio is 5:40, the product temperature is between 76 and 79 ℃, and the content of the extracted fraction is shown in the following table:
| time (minutes) | 1.9 (difluoro) | 2.1 (acid chloride) | 2.7 (unknown) | 3.2 (product) |
| Content (%) | 0.09 | / | / | 99.81 |
The contents of the products in the reaction kettle are shown in the following table:
| time (minutes) | 1.9 (difluoro) | 2.1 (acid chloride) | 2.7 (unknown) | 3.2 (product) |
| Content (%) | 0.05 | / | / | 99.85 |
As is clear from the above examples of the present invention, the quenching and washing with saturated sodium bicarbonate solution are more effective than saturated sodium carbonate solution, but the relative yield is low. The method has the advantages that the method is easy to obtain saturated sodium bicarbonate solution or saturated sodium carbonate solution, the market purchase price is low, the production cost is low, the equipment requirement is low, the purity of the 2, 2-ethyl difluoroacetate product manufactured and produced by the method is high, the manufacturing process is simple, the reaction process is mild, a producer can select different saturated alkaline aqueous solutions according to the input budget, the three wastes after the product production are simple to treat, and the method is suitable for large-scale popularization and production and has high economic benefit.
The above-described embodiments are only preferred embodiments of the present invention and should not be construed as limiting the scope of the invention, and thus, modifications, equivalent variations, improvements, etc. made in accordance with the claims of the present invention still fall within the scope of the invention.
Claims (6)
1. The preparation method of the low-cost and high-efficiency 2, 2-ethyl difluoroacetate is characterized by comprising the following steps of:
s1, under the protection of inert gas, difluoroethanol is added into a reaction container, acetyl chloride is slowly added dropwise under the low-temperature condition, and after the acetyl chloride is added dropwise, the reaction is continued in the reaction container for 0.5-2 h, so as to obtain a mixed solution A;
s2, based on S1, adding a saturated alkaline aqueous solution into the mixed solution A for quenching reaction, and then washing an organic phase to obtain a mixed solution B;
s3, based on S2, extracting and separating the mixed solution B, collecting an organic phase, and performing pressure rectification in a reaction kettle for 3 hours to obtain a finished product of the 2, 2-ethyl difluoroacetate.
2. The method for preparing the low-cost and high-efficiency ethyl 2, 2-difluoroacetate according to claim 1, which is characterized in that: in the step S1, the molar ratio of difluoroethanol to acetyl chloride in the reaction vessel is 1:1-2, and acetyl chloride is added dropwise at the temperature of 0-20 ℃.
3. The method for preparing the low-cost and high-efficiency ethyl 2, 2-difluoroacetate according to claim 2, wherein the method is characterized in that: in the step S1, the reaction temperature after the completion of the dropwise addition of the acetyl chloride is 30-60 ℃.
4. A process for the preparation of low cost, high efficiency ethyl 2, 2-difluoroacetate as defined in claim 3 wherein: in the step S2, the base of the saturated alkaline aqueous solution for quenching reaction is one of sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate.
5. A process for the preparation of low cost, high efficiency ethyl 2, 2-difluoroacetate as defined in claim 3 wherein: the alkali of the saturated alkaline aqueous solution for washing the organic phase is one of sodium carbonate, potassium carbonate, sodium bicarbonate or potassium bicarbonate.
6. The method for preparing the low-cost and high-efficiency ethyl 2, 2-difluoroacetate according to claim 4 or 5, wherein the method comprises the following steps of: in the step S3, the temperature of the reaction kettle is controlled within 100-150 ℃, and the extraction ratio of the fraction after rectification is 1: the temperature of the finished product of the ethyl 2, 2-difluoroacetate is 76-79 ℃ in the ratio of 40-10:40.
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