CN117843480B - Synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester and adopted synthesis device - Google Patents
Synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester and adopted synthesis device Download PDFInfo
- Publication number
- CN117843480B CN117843480B CN202410259878.0A CN202410259878A CN117843480B CN 117843480 B CN117843480 B CN 117843480B CN 202410259878 A CN202410259878 A CN 202410259878A CN 117843480 B CN117843480 B CN 117843480B
- Authority
- CN
- China
- Prior art keywords
- reaction
- trifluoro
- ethyl ester
- acid ethyl
- kettle
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000001308 synthesis method Methods 0.000 title claims abstract description 21
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 17
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 14
- 238000005886 esterification reaction Methods 0.000 claims abstract description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims abstract description 31
- 239000000463 material Substances 0.000 claims abstract description 22
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003960 organic solvent Substances 0.000 claims abstract description 16
- 238000007259 addition reaction Methods 0.000 claims abstract description 14
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 12
- 230000032050 esterification Effects 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 17
- 230000035484 reaction time Effects 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 238000004821 distillation Methods 0.000 claims description 8
- 230000002194 synthesizing effect Effects 0.000 claims 5
- 238000007086 side reaction Methods 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- OCJKUQIPRNZDTK-UHFFFAOYSA-N ethyl 4,4,4-trifluoro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)C(F)(F)F OCJKUQIPRNZDTK-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 238000003825 pressing Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000005265 energy consumption Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 1
- LIQBKSIZAXKCPA-UHFFFAOYSA-N 4,4,4-trifluoro-3-oxobutanoic acid Chemical compound OC(=O)CC(=O)C(F)(F)F LIQBKSIZAXKCPA-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000004812 organic fluorine compounds Chemical class 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005406 washing Methods 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
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of 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
- 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
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of 4, 4-trifluoro ethyl acetoacetate and a synthesis device adopted by the synthesis method. The synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester comprises the following steps: dissolving trifluoroacetyl chloride into an organic solvent under the conditions of 0.1-0.3MPa and minus 5-0 ℃, adding ketene into the organic solvent, and carrying out addition reaction through a tubular reactor B to obtain an intermediate material; adding ethanol into the intermediate material, and carrying out esterification reaction through a tubular reactor A to obtain a reaction liquid; rectifying the reaction liquid to obtain the 4, 4-trifluoro acetoacetic acid ethyl ester. The invention provides a synthesis method of 4, 4-trifluoro-acetoacetic acid ethyl ester, which reduces the occurrence of side reaction, has stable reaction condition, high reaction activity, high product purity and high yield, and also provides a synthesis device of 4, 4-trifluoro-acetoacetic acid ethyl ester.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of 4, 4-trifluoro ethyl acetoacetate and a synthesis device adopted by the synthesis method.
Background
The 4, 4-trifluoro acetoacetic acid ethyl ester is an important organic intermediate, is widely applied to industries such as organic fluorine compound synthesis, medicines, pesticides, dyes and the like, and can be used for preparing pesticides and medicines.
The existing synthesis process of the 4, 4-trifluoro-acetoacetic acid ethyl ester mainly uses sodium ethoxide or sodium hydride as a catalyst to promote ethyl acetate and trifluoro-acetic acid ethyl ester to carry out claisen ester condensation reaction, and then acidizing is carried out to synthesize the final product of the 4, 4-trifluoro-acetoacetic acid ethyl ester. However, the scheme has the problems of more reaction byproducts, difficult purification of products, lower yield, high reaction energy consumption, high price of the ethyl trifluoroacetate, high cost and the like.
Chinese patent CN103694119a discloses the following method: after adding an ethanol solution of sodium ethoxide, ethyl acetate and an organic solvent into a reactor, slowly adding the ethyl trifluoroacetate according to the change of the reaction temperature to prepare an intermediate of the ethyl trifluoroacetoacetate, then carrying out an acidification reaction after the temperature rising reaction, and finally filtering and washing the reaction solution after the temperature is reduced, and carrying out reduced pressure distillation to obtain the final product with the yield of 85 percent (purity 95 percent). The production process adopts sodium ethoxide solution as a catalyst to increase the safety and yield of the production process, but a plurality of small by-product organic matters exist in the product and the blockage of the positive reaction direction in the synthesis process is caused by the reasons of the claisen ester condensation reaction mechanism and the excessive ethanol.
The following method is disclosed in US4883904 a: preparing sodium ethoxide by using metallic sodium and ethanol, adding ethyl trifluoroacetate in a system with cyclohexane as an organic solvent in a cooling way, heating, adding ethyl acetate for reaction, desolventizing, adding cyclohexane, acidifying with anhydrous ethyl formate, and then carrying out subsequent distillation, reduced pressure distillation and reduced pressure rectification to finally obtain the product 4, 4-trifluoro ethyl acetoacetate (the product yield is 74.7 percent, and the product purity is 99.1 percent). In the method, unstable factors such as sodium metal exist in the sodium ethoxide preparation process, so that the process risk is high, the forward reaction is facilitated and the generation of side reactions is reduced after the dealcoholization is carried out twice, but the energy consumption of the process is high, and the energy consumption output is increased in the recovery process due to the excessive cyclohexane solvent.
Chinese patent CN113072449a discloses the following method: the method adopts trifluoroacetone and ethyl chloroformate as raw materials, hydrogen chloride as a catalyst, and the reaction is carried out in a pipeline reactor. The ethyl chloroformate with higher reactivity is adopted, and hydrogen chloride is used for catalytic reaction, so that the reaction time is shortened, the product yield is improved to a great extent, the production of high-purity products is not facilitated, and the ethyl chloroformate used as a product raw material has huge toxicity and has certain production safety hidden trouble.
Disclosure of Invention
The invention aims to overcome the defects in the prior art, provide a synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester, reduce the occurrence of side reaction, and has the advantages of stable reaction condition, high reaction activity, high product purity and high yield.
The synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester comprises the following steps:
(1) Dissolving trifluoroacetyl chloride into an organic solvent under the conditions of 0.1-0.3MPa and minus 5-0 ℃, adding ketene into the organic solvent, and carrying out addition reaction through a tubular reactor B to obtain an intermediate material; the organic solvent is dichloromethane or ethyl trifluoroacetate;
(2) Adding ethanol into the intermediate material, and carrying out esterification reaction through a tubular reactor A to obtain a reaction liquid;
(3) Rectifying the reaction liquid to obtain the 4, 4-trifluoro acetoacetic acid ethyl ester.
The molar ratio of ketene to trifluoroacetyl chloride in step (1) is (1:1) - (1:1.05).
The ethanol addition amount in the step (2) is added according to the molar ratio of ketene to ethanol of (1:1) - (1:1.05).
The addition reaction pressure of the step (1) is 0.1-0.3MPa, the reaction temperature is-5-0 ℃ and the reaction time is 1-2h.
The esterification reaction system temperature in the step (2) is 0-5 ℃, the reaction time is 2-3h, and the water bath temperature of the tubular reactor A is-8-0 ℃.
The adding time of dissolving the trifluoroacetyl chloride into the organic solvent in the step (1) is 50-70min, and the adding time of adding the ketene into the solution is 80-100min. The addition period refers to the period in which all the amounts are added uniformly.
The ethanol in the step (2) is added for 1-2h.
The rectification step of the step (3) comprises the steps of atmospheric distillation and then negative pressure distillation.
A synthesis device adopted by the synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester is as follows: the esterification reactor comprises an addition reactor, an esterification reactor, a tubular reactor A and a tubular reactor B, wherein the addition reactor is connected with the esterification reactor, the esterification reactor is circularly connected with the tubular reactor A, a condenser is arranged on the esterification reactor, and the addition reactor is circularly connected with the tubular reactor B.
The addition kettle is provided with a trifluoroacetyl chloride feeding pipe and a ketene feeding pipe, the esterification kettle is provided with an ethanol feeding pipe, and the tubular reactor A is an F46 tubular reactor A.
Specifically, the synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester comprises the following steps:
(1) Adding an organic solvent of dichloromethane or ethyl trifluoroacetate into an addition kettle, then opening a tubular reactor B for circular pre-cooling, slowly pressing trifluoroacetyl chloride into the addition kettle within 50-70min, stirring for dissolution and attaching a gas phase of 0.1-0.3MPa pressure, controlling the temperature to be-5-0 ℃, slowly pressing ketene into the addition kettle within 80-100min, controlling the temperature to be-5-0 ℃ and the pressure to be 0.1-0.3MPa for addition reaction, and obtaining an intermediate material; the molar ratio of ketene to trifluoroacetyl chloride was (1:1) - (1:1.05).
(2) Transferring the intermediate material into an esterification kettle, slowly adding ethanol into the esterification kettle for 1-2h, and performing temperature-controlled cyclic reaction through an F46 tubular reactor A, wherein the temperature of a water bath in the F46 tubular reactor A is controlled to be-8-0 ℃, the temperature of an esterification reaction system is controlled to be 0-5 ℃, and the reaction time is 2-3h, so as to obtain a reaction solution; during the esterification reaction, the generated hydrogen chloride is condensed and recovered by a condenser at the top of the esterification kettle, and the molar ratio of ketene to ethanol is (1:1) - (1:1.05).
(3) Rectifying the reaction liquid to obtain the 4, 4-trifluoro acetoacetic acid ethyl ester. The rectification is to distill the reaction liquid at normal pressure, distill the low boiling point solvent and a small amount of residual raw materials, then add the heavy component solvent (o-dichlorobenzene or high boiling point esters) into the distilled bottom material, distill the trifluoro acetoacetic acid ethyl ester out through negative pressure distillation, and the rectification is all conventional operation, so the parameters are not further limited, and the rectification is carried out according to the conventional rectification operation.
According to the invention, through a new synthetic route, first, ketene and trifluoroacetyl chloride are reacted to prepare an intermediate material, and the intermediate material is reacted with ethanol to prepare the 4, 4-trifluoroacetoacetate. The reaction structural formula is shown as follows:
。
Compared with the prior art, the invention has the following beneficial effects:
(1) The synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester has the advantages of less side reaction, high reaction activity, high reaction speed, low energy consumption and low cost.
(2) The synthetic method of the 4, 4-trifluoro acetoacetic acid ethyl ester has the advantages of high purity and high yield.
(3) By adopting the synthesis device, the synthesis reaction condition of the 4, 4-trifluoro acetoacetic acid ethyl ester is stable, and the reaction tends to be forward.
Drawings
FIG. 1 is a schematic diagram of a synthesis apparatus for ethyl 4, 4-trifluoroacetoacetate of the present invention.
In fig. 1: 1. an addition kettle; 2. an esterification kettle; 3. a tubular reactor A; 4. a condenser; 5. a trifluoroacetyl chloride feed tube; 6. a ketene feed tube; 7. an ethanol feed tube; 8. a tubular reactor B.
FIG. 2 is a gas chromatogram of ethyl 4, 4-trifluoroacetoacetate obtained in example 1.
Detailed Description
The invention will be further illustrated with reference to specific examples.
As shown in fig. 1, the synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester adopts a synthesis device: the esterification reaction kettle comprises an addition kettle 1, an esterification kettle 2, a tubular reactor A3 and a tubular reactor B8, wherein the addition kettle 1 is connected with the esterification kettle 2, the esterification kettle 2 is circularly connected with the tubular reactor A3, a condenser 4 is arranged on the esterification kettle 2, and the addition kettle 1 is circularly connected with the tubular reactor B8.
The addition kettle 1 is provided with a trifluoroacetyl chloride feeding pipe 5 and a ketene feeding pipe 6, the esterification kettle 2 is provided with an ethanol feeding pipe 7, and the tubular reactors A and B are F46 tubular reactors.
The connections are all well known to those skilled in the art, and the transfer of materials, including conventional pressure transfer and pump transfer, is conventional and will not be further discussed; the addition reactor 1, the esterification reactor 2, the tubular reactor A3 and the tubular reactor B8 are all conventional reaction kettles, so that the internal structures of the addition reactor 1, the esterification reactor 2, the tubular reactor A3 and the tubular reactor B8 are not described in any more way, and the tubular reactor B of the F46 tubular reactor A, F is a commercially available tubular reaction device, wherein an ice water bath (ethylene glycol aqueous solution) mode is adopted for keeping a constant temperature. The temperature of the addition water bath is controlled at-10- (-5) DEG C, the reaction temperature of the system is controlled at-5-0 ℃, the temperature of the esterification water bath is controlled at-8-0 ℃, the reaction temperature of the system is controlled at 0-5 ℃, and the system reaction is a slight exothermic reaction.
The following examples were all completed using the above-described apparatus.
Example 1
The synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester comprises the following steps:
(1) Adding 10kg of organic solvent methylene dichloride into an addition kettle 1, opening a tubular reactor B8 for circular pre-cooling, slowly pressing 2.87kg of trifluoroacetyl chloride (purity is 99.6%) into the addition kettle 1 within 60min, stirring for dissolution, controlling the pressure and temperature of the attached gas phase of 0.15MPa to be minus 5 ℃, slowly pressing 0.89kg of ketene (purity is 98.65%) into the addition kettle 1 within 90min, controlling the temperature to be minus 5 ℃ and the pressure to be 0.2MPa, and carrying out addition reaction to obtain an intermediate material.
(2) Transferring the intermediate material into an esterification kettle 2, slowly adding 0.968kg of ethanol (purity is 99.5%) into the esterification kettle 2 for 1.5h, and performing temperature-controlled cyclic reaction through a tubular reactor A3, wherein the water bath temperature in the tubular reactor A3 is controlled to be-5 ℃, the temperature of an esterification reaction system is controlled to be 2 ℃, and the reaction time is 2h, so as to obtain a reaction liquid; during the esterification reaction, the generated hydrogen chloride is separated and recovered by a condenser 4 at the top of the esterification reactor 2.
(3) The reaction liquid is rectified to obtain 3.561kg of 4, 4-trifluoro-acetoacetate, the yield is 92.25% (calculated by ketene pure substance and 4, 4-trifluoro-acetoacetate pure substance), the purity is 99.67%, the gas chromatographic detection diagram of the prepared 4, 4-trifluoro-acetoacetate is shown in figure 2, when the retention time is 5.455min, the peak area of the ethyl acetate is 38909, the retention time is 10.679min, the peak area of the 4, 4-trifluoro-acetoacetate is 12056161.
Example 2
The synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester comprises the following steps:
(1) Adding 10kg of organic solvent methylene dichloride into an addition kettle 1, opening a tubular reactor B8 for circular pre-cooling, slowly pressing 2.84kg of trifluoroacetyl chloride (purity is 99.6%) into the addition kettle 1 within 70min, stirring for dissolution, controlling the pressure and temperature of the attached gas phase of 0.1MPa to be minus 2 ℃, slowly pressing 0.89kg of ketene (purity is 98.65%) into the addition kettle 1 within 90min, controlling the temperature to be minus 2 ℃ and the pressure to be 0.1MPa, and carrying out addition reaction to obtain an intermediate material.
(2) Transferring the intermediate material into an esterification kettle 2, slowly adding 0.975kg of ethanol (99.5%) into the esterification kettle 2 for 1.5h, and performing temperature-controlled cyclic reaction through a tubular reactor A3, wherein the water bath temperature in the tubular reactor A3 is controlled to be-5 ℃, the temperature of an esterification reaction system is controlled to be 2 ℃, and the reaction time is 2h, so as to obtain a reaction liquid; during the esterification reaction, the generated hydrogen chloride is separated and recovered by a condenser 4 at the top of the esterification reactor 2.
(3) The reaction mixture was distilled to obtain 3.57kg of ethyl 4, 4-trifluoroacetoacetate with a yield of 92.3% (based on the pure ketene and ethyl 4, 4-trifluoroacetoacetate) and a purity of 99.5%.
Example 3
The synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester comprises the following steps:
(1) Adding 10kg of organic solvent ethyl trifluoroacetate into an addition kettle 1, opening a tubular reactor B8 for circular pre-cooling, slowly pressing 2.83kg of trifluoroacetyl chloride (99.6%) into the addition kettle 1 within 50min, stirring for dissolution, controlling the pressure and temperature of the attached gas phase to be-2 ℃, slowly pressing 0.89kg of ketene (98.65%) into the addition kettle 1 within 80min, controlling the temperature to be-2 ℃ and the pressure to be 0.25MPa, and carrying out addition reaction to obtain an intermediate material.
(2) Transferring the intermediate material into an esterification kettle 2, slowly adding 0.97kg of ethanol (99.5%) into the esterification kettle 2 for 1h, and performing temperature-controlled cyclic reaction through a tubular reactor A3, wherein the water bath temperature in the tubular reactor A3 is controlled to be 0 ℃, the temperature of an esterification reaction system is controlled to be 5 ℃, and the reaction time is 3h, so as to obtain a reaction liquid; during the esterification reaction, the generated hydrogen chloride is separated and recovered by a condenser 4 at the top of the esterification reactor 2.
(3) The reaction mixture was distilled to obtain 3.54kg of ethyl 4, 4-trifluoroacetoacetate in 91.5% yield (based on pure ketene and pure ethyl 4, 4-trifluoroacetoacetate) and 99.45% purity.
Example 4
The synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester comprises the following steps:
(1) Adding 12kg of organic solvent methylene dichloride into an addition kettle 1, opening a tubular reactor B8 for circular pre-cooling, slowly pressing 2.89kg of trifluoroacetyl chloride (99.6%) into the addition kettle 1 within 60min, stirring for dissolution, controlling the pressure and temperature of the attached gas phase of 0.3MPa to be 0 ℃, slowly pressing 0.89kg of ketene (98.65%) into the addition kettle 1 within 100min, controlling the temperature to be 0 ℃ and the pressure to be 0.3MPa, and carrying out addition reaction to obtain an intermediate material.
(2) Transferring the intermediate material into an esterification kettle 2, slowly adding 0.98kg of ethanol (99.5%) into the esterification kettle 2 for 2 hours, and performing temperature-controlled cyclic reaction through a tubular reactor A3, wherein the water bath temperature in the tubular reactor A3 is controlled to be-5 ℃, the temperature of an esterification reaction system is controlled to be 2 ℃, and the reaction time is 3 hours, so as to obtain a reaction solution; during the esterification reaction, the generated hydrogen chloride is separated and recovered by a condenser 4 at the top of the esterification reactor 2.
(3) The reaction mixture was distilled to obtain 3.558kg of ethyl 4, 4-trifluoroacetoacetate, with a yield of 92% (based on pure ketene and pure ethyl 4, 4-trifluoroacetoacetate) and a purity of 99.5%.
Comparative example 1
The device used in this comparative example is shown in FIG. 1, but the tubular reactor B8 in FIG. 1 is removed, and the mode of maintaining the temperature by circulating pre-cooling is changed to a mode of maintaining the temperature by circulating water in the jacket of the outer wall of the addition reactor 1 itself. The synthesis process and ingredients of the 4, 4-trifluoro-acetoacetate are the same as those of the example 1, and 1.924kg of 4, 4-trifluoro-acetoacetate is finally obtained, the yield is 35% (calculated by pure substances of ketene and trifluoro-acetoacetate) and the purity is 70%.
Comparative example 2
The comparative example adopts a device shown in fig. 1, and a synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester comprises the following steps:
(1) 10kg of organic solvent methylene dichloride is added into an addition kettle 1, then a tubular reactor B8 is opened for circular precooling, 0.297kg of ketene (purity 98.65%) is slowly pressed into the addition kettle 1 within 20min, the mixture is stirred and dissolved, the pressure and temperature of the attached gas phase of 0.15MPa are controlled at-5 ℃, then 0.957kg of trifluoroacetyl chloride (purity 99.6%) is slowly pressed into the addition kettle 1 within 30min, the temperature is controlled at-5 ℃ and the pressure is controlled at 0.2MPa, the addition reaction is carried out, and the addition reaction (finally, 0.89kg of ketene and 2.87kg of trifluoroacetyl chloride) are added) is repeatedly carried out to obtain intermediate materials.
(2) Transferring the intermediate material into an esterification kettle 2, slowly adding 0.968kg of ethanol (purity is 99.5%) into the esterification kettle 2 for 1.5h, and performing temperature-controlled cyclic reaction through a tubular reactor A3, wherein the water bath temperature in the tubular reactor A3 is controlled to be-5 ℃, the temperature of an esterification reaction system is controlled to be 2 ℃, and the reaction time is 2h, so as to obtain a reaction liquid; during the esterification reaction, the generated hydrogen chloride is condensed and recovered by a condenser 4 at the top of the esterification reactor 2.
(3) The reaction solution was distilled to obtain 3.2kg of ethyl 4, 4-trifluoroacetoacetate, with a yield of 74% (based on the pure ketene and ethyl trifluoroacetoacetate) and a purity of 89%.
Comparative example 3
In this comparative example, the addition reaction temperature of the addition step of (1) was changed from-5℃to 20℃and the pressure was adjusted to 0.3MPa by the temperature change, except that the addition reaction temperature of the addition of trifluoroacetyl chloride and ketene was changed from-5℃to 0.3 MPa. The final yield of ethyl 4, 4-trifluoroacetoacetate was 0.628kg, 8% (calculated on ketene pure and ethyl trifluoroacetoacetate pure) and the purity was 49%.
Claims (6)
1. A synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester is characterized in that: the method comprises the following steps:
(1) Adding an organic solvent and trifluoroacetyl chloride into an addition kettle, adding ketene into the addition kettle under the conditions of 0.1-0.3MPa and minus 5-0 ℃, and carrying out an addition reaction by a tubular reactor B, wherein the addition reaction pressure is 0.1-0.3MPa, the reaction temperature is minus 5-0 ℃ and the reaction time is 1-2 hours, so as to obtain an intermediate material;
(2) Transferring the intermediate material into an esterification kettle, adding ethanol, and carrying out esterification reaction through a tubular reactor A, wherein the temperature of an esterification reaction system is 0-5 ℃, the reaction time is 2-3h, and the water bath temperature of the tubular reactor A is-8-0 ℃ to obtain a reaction liquid;
(3) Rectifying the reaction solution to obtain 4, 4-trifluoro acetoacetic acid ethyl ester;
The synthesis method of the 4, 4-trifluoro acetoacetic acid ethyl ester adopts a synthesis device: the method comprises an addition kettle (1), an esterification kettle (2), a tubular reactor A (3) and a tubular reactor B (8), wherein the addition kettle (1) is connected with the esterification kettle (2), the esterification kettle (2) is circularly connected with the tubular reactor A (3), a condenser (4) is arranged on the esterification kettle (2), and the addition kettle (1) is circularly connected with the tubular reactor B (8);
the addition kettle (1) is provided with a trifluoroacetyl chloride feeding pipe (5) and a ketene feeding pipe (6), and the esterification kettle (2) is provided with an ethanol feeding pipe (7).
2. The method for synthesizing 4, 4-trifluoro acetoacetic acid ethyl ester according to claim 1, which is characterized in that: the molar ratio of ketene to trifluoroacetyl chloride in step (1) is (1:1) - (1:1.05).
3. The method for synthesizing 4, 4-trifluoro acetoacetic acid ethyl ester according to claim 1, which is characterized in that: the ethanol addition amount in the step (2) is added according to the molar ratio of ketene to ethanol of (1:1) - (1:1.05).
4. The method for synthesizing 4, 4-trifluoro acetoacetic acid ethyl ester according to claim 1, which is characterized in that: the adding time of dissolving the trifluoroacetyl chloride into the organic solvent in the step (1) is 50-70min, and the adding time of adding the ketene into the solution is 80-100min.
5. The method for synthesizing 4, 4-trifluoro acetoacetic acid ethyl ester according to claim 1, which is characterized in that: the ethanol in the step (2) is added for 1-2h.
6. The method for synthesizing 4, 4-trifluoro acetoacetic acid ethyl ester according to claim 1, which is characterized in that: the rectification step of the step (3) comprises the steps of atmospheric distillation and then negative pressure distillation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410259878.0A CN117843480B (en) | 2024-03-07 | 2024-03-07 | Synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester and adopted synthesis device |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410259878.0A CN117843480B (en) | 2024-03-07 | 2024-03-07 | Synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester and adopted synthesis device |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN117843480A CN117843480A (en) | 2024-04-09 |
| CN117843480B true CN117843480B (en) | 2024-05-14 |
Family
ID=90543776
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410259878.0A Active CN117843480B (en) | 2024-03-07 | 2024-03-07 | Synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester and adopted synthesis device |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117843480B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1310174A (en) * | 1963-03-06 | |||
| GB931689A (en) * | 1960-12-17 | 1963-07-17 | Hoechst Ag | Process for the manufacture of fluorinated acetoacetic acid chlorides and the solutions thereof |
| CN102317252A (en) * | 2009-02-19 | 2012-01-11 | 苏威氟有限公司 | Compositions of esters of fluorosubstituted alcanoic acids |
| CN116396165A (en) * | 2023-03-24 | 2023-07-07 | 宁夏思科达生物科技有限公司 | Production process of 4-chloroacetoacetic acid ethyl ester |
-
2024
- 2024-03-07 CN CN202410259878.0A patent/CN117843480B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1310174A (en) * | 1963-03-06 | |||
| GB931689A (en) * | 1960-12-17 | 1963-07-17 | Hoechst Ag | Process for the manufacture of fluorinated acetoacetic acid chlorides and the solutions thereof |
| CN102317252A (en) * | 2009-02-19 | 2012-01-11 | 苏威氟有限公司 | Compositions of esters of fluorosubstituted alcanoic acids |
| CN116396165A (en) * | 2023-03-24 | 2023-07-07 | 宁夏思科达生物科技有限公司 | Production process of 4-chloroacetoacetic acid ethyl ester |
Non-Patent Citations (1)
| Title |
|---|
| 上海市经济团体联合会，上海市化学化工学会编.《节能减排理论基础与装备技术》.华东理工大学出版社,2010,(第1版),第273页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN117843480A (en) | 2024-04-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112028755B (en) | Method for preparing 1,3 cyclohexanedione | |
| WO2019119934A1 (en) | Method for continuous preparation of 2-methyl allyl alcohol | |
| CN113480421B (en) | System and method for preparing succinic acid by maleic anhydride hydrogenation | |
| CN117142954A (en) | Preparation method of ethyl 4, 4-trifluoroacetoacetate | |
| CN117843480B (en) | Synthesis method of 4, 4-trifluoro acetoacetic acid ethyl ester and adopted synthesis device | |
| CN113336629A (en) | Preparation process of 1,3 cyclohexanedione | |
| CN111808054A (en) | Preparation method of ionic liquid and application of ionic liquid in cyclohexanone synthesis | |
| CN113072449B (en) | Synthesis method of 4,4, 4-trifluoroacetylacetic acid ethyl ester | |
| CN113754528A (en) | Preparation method of cyclopentanecarboxylic acid | |
| CN106986900B (en) | A kind of preparation method of N- alkyl glucose imines | |
| CN112321399B (en) | Preparation method of chemical intermediate | |
| CN102070693A (en) | Method for preparing ursodesoxycholic acid by chiral catalytic hydrogenation of 7-ketodesoxycholic acid | |
| CN214528133U (en) | Continuous flow method synthesis system of bromine chloride | |
| CN114349633A (en) | Process for the preparation of diesters of glutaconic acid | |
| CN118637999B (en) | 1, 1-Trifluoroacetone and synthesis method and synthesis device thereof | |
| CN215049791U (en) | Production system of 4-methyl-5-thiazole ethanol | |
| CN114685410B (en) | Preparation method of butylphthalide | |
| CN114685405B (en) | Method for continuously preparing D, L-pantolactone | |
| CN111995566B (en) | Synthesis method of 2-hydroxyethyl pyridine | |
| CN118084638A (en) | Continuous production method and device of 1, 3-cyclohexanedione | |
| CN116621709B (en) | Synthesis method of cyclopropylamine | |
| CN118125918B (en) | Continuous synthesis method and synthesis device of 4, 4-trifluoro acetoacetic acid ethyl ester | |
| CN114478203B (en) | Preparation method of vinyl low-carbon alcohol for polyether initiator | |
| CN115785018A (en) | Preparation method of febuxostat decarboxylated impurities | |
| CN116606198A (en) | Preparation method of 1, 3-cyclohexanedione |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |