CN116063178A - Synthesis method of ethyl trifluoroacetoacetate - Google Patents
Synthesis method of ethyl trifluoroacetoacetate Download PDFInfo
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- CN116063178A CN116063178A CN202111290760.7A CN202111290760A CN116063178A CN 116063178 A CN116063178 A CN 116063178A CN 202111290760 A CN202111290760 A CN 202111290760A CN 116063178 A CN116063178 A CN 116063178A
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- Prior art keywords
- ethyl
- reaction
- trifluoroacetoacetate
- trifluoroacetate
- stirring
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- 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 title claims abstract description 33
- 238000001308 synthesis method Methods 0.000 title claims abstract description 10
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 claims abstract description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims abstract description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 57
- 238000006243 chemical reaction Methods 0.000 claims description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- 235000019441 ethanol Nutrition 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 12
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 claims 3
- 238000000034 method Methods 0.000 claims 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003512 Claisen condensation reaction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000005886 esterification reaction Methods 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000004821 distillation Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- ZOWSJJBOQDKOHI-UHFFFAOYSA-N 2,2,2-trifluoroethyl acetate Chemical compound CC(=O)OCC(F)(F)F ZOWSJJBOQDKOHI-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
-
- 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
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic 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 ethyl trifluoroacetoacetate. According to the invention, trifluoroacetic acid is used as a raw material, an intermediate ethyl trifluoroacetate is synthesized through esterification reaction, and then claisen condensation reaction is carried out, so that ethyl trifluoroacetoacetate is effectively synthesized, and the synthesis yield are improved.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of ethyl trifluoroacetoacetate.
Background
The trifluoro acetoacetic acid ethyl ester is an important intermediate for synthesizing fluorine-containing compounds such as pesticides, medicines and the like, and can be used as a raw material or a key intermediate for producing various heterocyclic medicaments, high-efficiency pesticides and high-efficiency herbicides or obtaining the important intermediate for synthesizing the products. The products developed at present are pyridine, pyrimidine, pyrrole, sulfonylurea compounds, fluorine-containing organic acids and salts thereof, and the like. In view of the important application of the trifluoro acetoacetic acid ethyl ester, the synthesis technology of the trifluoro acetoacetic acid ethyl ester is further researched and optimized, and the trifluoro acetoacetic acid ethyl ester has important significance in accelerating the industrial production and application.
At present, the synthesis of the ethyl trifluoroacetoacetate mainly adopts claisen condensation of the ethyl trifluoroacetoacetate and the ethyl acetate in an inert solvent under the action of strong alkali, but the yield and purity of the synthesized ethyl trifluoroacetoacetate are lower.
Disclosure of Invention
The synthesis method of the ethyl trifluoroacetoacetate is characterized by comprising the following steps of:
(1) Placing absolute ethyl alcohol and trifluoroacetic acid into a reactor for stirring, adding concentrated sulfuric acid, heating to reflux, stirring, and cooling to obtain an intermediate ethyl trifluoroacetate; the chemical formula is:
(2) Placing intermediate ethyl trifluoroacetate into a reaction kettle, setting the temperature to be 13-18 ℃, adding sodium ethoxide and ethanol, carrying out heat preservation reaction, adding ethyl acetate, carrying out reaction, generating the temperature to be 40-50 ℃, continuing the reaction, and ending the reaction to obtain ethyl trifluoroacetoacetate.
Preferably, in the step (1), the mass ratio of the absolute ethyl alcohol, the trifluoroacetic acid and the concentrated sulfuric acid is 15:5 to 7:0.3 to 1.1.
Preferably, the mass ratio of the intermediate ethyl trifluoroacetate, sodium ethylate and ethyl acetate in the step (2) is 5:11 to 13:10 to 12.
The beneficial effects are that:
according to the invention, trifluoroacetic acid is used as a raw material, an intermediate ethyl trifluoroacetate is synthesized through esterification reaction, and then claisen condensation reaction is carried out, so that ethyl trifluoroacetoacetate is effectively synthesized, and the synthesis yield are improved.
Detailed Description
The synthesis method of the ethyl trifluoroacetoacetate is characterized by comprising the following steps of:
(1) The mass ratio of the absolute ethyl alcohol to the trifluoroacetic acid to the concentrated sulfuric acid is 15:5 to 7:0.3 to 1.1, taking materials, putting absolute ethyl alcohol and trifluoroacetic acid into a reactor, stirring, adding concentrated sulfuric acid, heating to reflux, stirring, and cooling to obtain an intermediate ethyl trifluoroacetate;
(2) According to the mass ratio of the intermediate trifluoro ethyl acetate, sodium ethylate ethanol and ethyl acetate of 5:11 to 13: 10-12, taking materials, putting an intermediate ethyl trifluoroacetate into a reaction kettle, setting the temperature to be 13-18 ℃, adding sodium ethylate and ethanol, carrying out heat preservation reaction, adding ethyl acetate, carrying out reaction, generating the temperature to be 40-50 ℃, continuing the reaction, and ending the reaction to obtain the ethyl trifluoroacetoacetate.
Example 1
The synthesis method of the ethyl trifluoroacetoacetate is characterized by comprising the following steps of:
(1) Putting 1500kg of absolute ethyl alcohol and 500kg of trifluoroacetic acid into a reactor, stirring, adding 30kg of concentrated sulfuric acid, heating to reflux, stirring for 7h, cooling to 35 ℃, recovering solvent ethanol by reduced pressure distillation, recovering ethanol, and after the recovery of the ethanol is finished, distilling under reduced pressure to roughly distill intermediate ethyl trifluoroacetate, and pumping the crude ethyl trifluoroacetate into a rectifying kettle to obtain intermediate ethyl trifluoroacetate with the yield of 93.4% and the purity of 97.9%;
(2) 500kg of intermediate ethyl trifluoroacetate is put into a reaction kettle, the set temperature is 13 ℃, 1100kg of sodium ethylate ethanol is added, the reaction is carried out for 1.5 hours while the temperature is kept, 1000kg of ethyl acetate is added, the reaction is carried out for 2 hours, the temperature is raised to 40 ℃, the reaction is continued for 4 hours, the reaction is finished, the quenching reaction is carried out, toluene is added for extraction, layering, toluene organic phase solution is transferred into a water diversion kettle, water is returned and separated, then toluene is recovered, crude ethyl trifluoroacetoacetate is obtained, the crude ethyl trifluoroacetoacetate is transferred into a rectifying kettle, the yield of the ethyl trifluoroacetoacetate is 94.7%, and the purity is 98.1%.
Example 2
The synthesis method of the ethyl trifluoroacetoacetate is characterized by comprising the following steps of:
(1) Putting 1500kg of absolute ethyl alcohol and 600kg of trifluoroacetic acid into a reactor, stirring, adding 60kg of concentrated sulfuric acid, heating to reflux, stirring for 7 hours, cooling to 35 ℃, recovering solvent ethanol by reduced pressure distillation, recovering the ethanol, and after the recovery of the ethanol is finished, distilling the crude product of the ethyl trifluoroacetate by reduced pressure distillation, and pumping the crude product of the ethyl trifluoroacetate into a rectifying kettle to obtain the intermediate of the ethyl trifluoroacetate, wherein the yield is 97.8 percent and the purity is 98.8 percent;
(2) 500kg of intermediate ethyl trifluoroacetate is put into a reaction kettle, the set temperature is 15 ℃, 1200kg of sodium ethylate ethanol is added, the reaction is carried out for 1.5 hours while the temperature is kept, 1100kg of ethyl acetate is added, the reaction is carried out for 2 hours, the temperature is raised to 45 ℃, the reaction is continued for 4 hours, the reaction is finished, the quenching reaction is carried out, toluene is added for extraction, layering, toluene organic phase solution is transferred into a water diversion kettle, water diversion is carried out in a reflux manner, toluene is recovered, crude ethyl trifluoroacetoacetate is obtained, the crude ethyl trifluoroacetoacetate is transferred into a rectifying kettle, the yield of the ethyl trifluoroacetoacetate is 98.7%, and the purity is 99.3%.
Example 3
The synthesis method of the ethyl trifluoroacetoacetate is characterized by comprising the following steps of:
(1) Putting 1500kg of absolute ethyl alcohol and 700kg of trifluoroacetic acid into a reactor, stirring, adding 110kg of concentrated sulfuric acid, heating to reflux, stirring for 7h, cooling to 35 ℃, recovering solvent ethanol by reduced pressure distillation, recovering the ethanol, and after the recovery of the ethanol is finished, distilling the crude product of the ethyl trifluoroacetate by reduced pressure distillation, and pumping the crude product of the ethyl trifluoroacetate into a rectifying kettle to obtain the intermediate of the ethyl trifluoroacetate, wherein the yield is 93.8 percent and the purity is 95.8 percent;
(2) 500kg of intermediate ethyl trifluoroacetate is put into a reaction kettle, the set temperature is 18 ℃, 1300kg of sodium ethylate ethanol is added, the reaction is carried out for 1.5 hours while the temperature is kept, 1200kg of ethyl acetate is added, the reaction is carried out for 2 hours, the temperature is raised to 50 ℃, the reaction is continued for 4 hours, the reaction is finished, the quenching reaction is carried out, toluene is added for extraction, layering, toluene organic phase solution is transferred into a water diversion kettle, water is returned and separated, then toluene is recovered, crude ethyl trifluoroacetoacetate is obtained, the crude ethyl trifluoroacetoacetate is transferred into a rectifying kettle, the yield of the ethyl trifluoroacetoacetate is 95.7%, and the purity is 94.8%.
Claims (3)
1. The synthesis method of the ethyl trifluoroacetoacetate is characterized by comprising the following steps of:
(1) Placing absolute ethyl alcohol and trifluoroacetic acid into a reactor for stirring, adding concentrated sulfuric acid, heating to reflux, stirring, and cooling to obtain an intermediate ethyl trifluoroacetate; the chemical formula is:
(2) Placing intermediate ethyl trifluoroacetate into a reaction kettle, setting the temperature to be 13-18 ℃, adding sodium ethoxide and ethanol, carrying out heat preservation reaction, adding ethyl acetate, carrying out reaction, generating the temperature to be 40-50 ℃, continuing the reaction, and ending the reaction to obtain ethyl trifluoroacetoacetate;
2. the method for synthesizing ethyl trifluoroacetoacetate according to claim 1, wherein the mass ratio of absolute ethyl alcohol, trifluoroacetic acid and concentrated sulfuric acid in the step (1) is 15:5 to 7:0.3 to 1.1.
3. The method for synthesizing the ethyl trifluoroacetoacetate according to claim 1, wherein the mass ratio of the intermediates of the step (2) including ethyl trifluoroacetate, sodium ethylate and ethyl acetate is 5:11 to 13:10 to 12.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111290760.7A CN116063178A (en) | 2021-11-03 | 2021-11-03 | Synthesis method of ethyl trifluoroacetoacetate |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111290760.7A CN116063178A (en) | 2021-11-03 | 2021-11-03 | Synthesis method of ethyl trifluoroacetoacetate |
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| Publication Number | Publication Date |
|---|---|
| CN116063178A true CN116063178A (en) | 2023-05-05 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111290760.7A Pending CN116063178A (en) | 2021-11-03 | 2021-11-03 | Synthesis method of ethyl trifluoroacetoacetate |
Country Status (1)
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4647689A (en) * | 1982-07-30 | 1987-03-03 | Monsanto Company | Preparation of alkyl trifluoroacetoacetate |
| US4879407A (en) * | 1986-10-16 | 1989-11-07 | Rhone-Poulenc Chimie | Process for the preparation of ethyl trifluoroacetate |
| KR20110001415A (en) * | 2009-06-30 | 2011-01-06 | 주식회사 대희화학 | New synthetic method of 4,4,4-trifluoro-1-(4-methylphenyl) butane-1,3-dione |
| CN103694119A (en) * | 2012-09-28 | 2014-04-02 | 中化蓝天集团有限公司 | Preparation method of ethyl 4,4,4-trifluoroacetoacetate |
| CN113372264A (en) * | 2021-06-16 | 2021-09-10 | 宁夏常晟药业有限公司 | Synthetic method of 2- [ 2-methyl-3- (trifluoromethyl) phenylamino ] nicotinic acid |
| CN113512011A (en) * | 2021-05-15 | 2021-10-19 | 宁夏常晟药业有限公司 | Synthetic method of 2-methylsulfonyl-5-trifluoromethyl-1, 3, 4-thiadiazole |
-
2021
- 2021-11-03 CN CN202111290760.7A patent/CN116063178A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4647689A (en) * | 1982-07-30 | 1987-03-03 | Monsanto Company | Preparation of alkyl trifluoroacetoacetate |
| US4879407A (en) * | 1986-10-16 | 1989-11-07 | Rhone-Poulenc Chimie | Process for the preparation of ethyl trifluoroacetate |
| KR20110001415A (en) * | 2009-06-30 | 2011-01-06 | 주식회사 대희화학 | New synthetic method of 4,4,4-trifluoro-1-(4-methylphenyl) butane-1,3-dione |
| CN103694119A (en) * | 2012-09-28 | 2014-04-02 | 中化蓝天集团有限公司 | Preparation method of ethyl 4,4,4-trifluoroacetoacetate |
| CN113512011A (en) * | 2021-05-15 | 2021-10-19 | 宁夏常晟药业有限公司 | Synthetic method of 2-methylsulfonyl-5-trifluoromethyl-1, 3, 4-thiadiazole |
| CN113372264A (en) * | 2021-06-16 | 2021-09-10 | 宁夏常晟药业有限公司 | Synthetic method of 2- [ 2-methyl-3- (trifluoromethyl) phenylamino ] nicotinic acid |
Non-Patent Citations (2)
| Title |
|---|
| 张金玉等著: "有机合成反应及路线设计研究", 31 May 2021, 中国原子能出版社, pages: 255 * |
| 赵临襄主编: "化学制药工艺学", 31 August 2015, 中国医药科技出版社, pages: 232 * |
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