CN104072357A - Synthetic method for difluoroethanoic acid - Google Patents
Synthetic method for difluoroethanoic acid Download PDFInfo
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- CN104072357A CN104072357A CN201410316051.5A CN201410316051A CN104072357A CN 104072357 A CN104072357 A CN 104072357A CN 201410316051 A CN201410316051 A CN 201410316051A CN 104072357 A CN104072357 A CN 104072357A
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- acetic acid
- difluoroethanoic
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/06—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid amides
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Abstract
The invention discloses a synthetic method for difluoroethanoic acid. The synthetic method comprises the following steps: adding diethylamine and an organic solvent into a reaction device, uniformly mixing, controlling a reaction temperature to 10-20 DEG C, slowly dropwise adding dichloroacetyl chloride within about 2 hours, filtering and distilling to obtain a product N, N- diethylchloroacetamide after reaction is ended; mixing the N, N- diethylchloroacetamide, dried anhydrous potassium fluoride and sulfolane, reacting for 6-8 hours at 120-140 DEG C, treating to obtain a product N, N- diethyldifluoroacetamide; mixing the N, N- diethyldifluoroacetamide with 10-20wt% sodium hydroxide or potassium hydroxide aqueous liquor, refluxing for reacting for over 4 hours, and acidifying, extracting and distilling to obtain the difluoroethanoic acid. According to the synthetic method for the difluoroethanoic acid, which is disclosed by the invention, yield of the difluoroethanoic acid is over 92%; the method is gentle in reaction condition, and the difluoroethanoic acid is easy to separate and stable while being heated, and easy for industrial production.
Description
Technical field
The invention belongs to fine chemical technology field, relate to a kind of synthetic method of difluoro acetic acid.
Background technology
The introducing of fluoro-containing group often can improve the biological activity of compound, and difluoromethyl group is considered to polar body such as grade and the isostere of hydroxyl, introduces difluoromethyl and can give the biological activity that compound is new in compound.Difluoro acetic acid, is widely used as in catalyzer, medicine intermediate, agrochemistry and functional materials synthetic containing the chemical of difluoromethyl as foundation class, and therefore, research is simple, difluoro acetic acid synthetic method has important practical significance efficiently.
Summary of the invention
In view of this, the object of the present invention is to provide a kind of novel synthesis of difluoro acetic acid.
For achieving the above object, the invention provides following technical scheme:
A synthetic method for difluoro acetic acid, comprises the steps:
(1) diethylamine and organic solvent are added in reaction unit, mix, control 10 ~ 20 ℃ of temperature of reaction, in 2h, slowly splash into dichloroacetyl chloride, react complete, after filtration, distillation obtain product N, N-diethyl dichloro acetamide, the mol ratio of described diethylamine and dichloroacetyl chloride is 1:0.3 ~ 0.4;
In technique scheme, described organic solvent is benzene or toluene.
Preferably, the mol ratio of described diethylamine and dichloroacetyl chloride is 1:0.35.
(2) by N, N-diethyl dichloro acetamide, dry anhydrous potassium fluoride or Sodium Fluoride and tetramethylene sulfone mix, 120 ~ 140 ℃ of reaction 6 ~ 8h, the treated product N that obtains, N-diethyl two monofluoroacetamides, described N, the mol ratio of N-diethyl dichloro acetamide, anhydrous potassium fluoride or Sodium Fluoride and tetramethylene sulfone is 1:2 ~ 3:1 ~ 1.5;
Preferably, by N, N-diethyl dichloro acetamide, dry anhydrous potassium fluoride or Sodium Fluoride and tetramethylene sulfone mix, 130 ℃ of reaction 7h.
Preferably, described N, the mol ratio of N-diethyl dichloro acetamide, anhydrous potassium fluoride or Sodium Fluoride and tetramethylene sulfone is 1:2.5:1.2.
(3), by N, N-diethyl two monofluoroacetamides and 10 ~ 20wt% sodium hydroxide or potassium hydroxide aqueous solution mix, and more than back flow reaction 4h, through acidifying, extraction, distillation, obtain difluoro acetic acid.
The synthetic method of difluoro acetic acid of the present invention, the difluoro acetic acid productive rate of gained is more than 92%, and the method reaction conditions is gentle, product is easily separated and it is thermally-stabilised to be subject to, and is easy to suitability for industrialized production.
Embodiment
Below the technical scheme in the embodiment of the present invention is described in detail, obviously, described embodiment is only the present invention's part embodiment, rather than whole embodiment.Embodiment based in the present invention, the every other embodiment that those of ordinary skills obtain under the prerequisite of not making creative work, belongs to the scope of protection of the invention.
Embodiment 1
(1) diethylamine and organic solvent-benzene are added in reaction unit, mix, control 10 ℃ of temperature of reaction, in 2h, slowly splash into dichloroacetyl chloride, react complete, after filtration, distillation obtain product N, N-diethyl dichloro acetamide, the mol ratio of described diethylamine and dichloroacetyl chloride is 1:0.3;
(2), by N, N-diethyl dichloro acetamide, dry anhydrous potassium fluoride and tetramethylene sulfone mix, 120 ℃ of reaction 8h, the treated product N that obtains, N-diethyl two monofluoroacetamides, described N, the mol ratio of N-diethyl dichloro acetamide, anhydrous potassium fluoride and tetramethylene sulfone is 1:2:1;
(3), by N, N-diethyl two monofluoroacetamides and 10wt% aqueous sodium hydroxide solution mix, and more than back flow reaction 4h, through acidifying, extraction, distillation, obtain difluoro acetic acid, productive rate 92.2%.
Embodiment 2
(1) diethylamine and organic solvent toluene are added in reaction unit, mix, control 20 ℃ of temperature of reaction, in 2h, slowly splash into dichloroacetyl chloride, react complete, after filtration, distillation obtain product N, N-diethyl dichloro acetamide, the mol ratio of described diethylamine and dichloroacetyl chloride is 1:0.4;
(2), by N, N-diethyl dichloro acetamide, dry anhydrous Sodium Fluoride and tetramethylene sulfone mix, 140 ℃ of reaction 6h, the treated product N that obtains, N-diethyl two monofluoroacetamides, described N, the mol ratio of N-diethyl dichloro acetamide, anhydrous Sodium Fluoride and tetramethylene sulfone is 1:3:1.5;
(3), by N, N-diethyl two monofluoroacetamides and 20wt% potassium hydroxide aqueous solution mix, and more than back flow reaction 4h, through acidifying, extraction, distillation, obtain difluoro acetic acid, productive rate 92.6%.
Embodiment 3
(1) diethylamine and organic solvent-benzene are added in reaction unit, mix, control 15 ℃ of temperature of reaction, in 2h, slowly splash into dichloroacetyl chloride, react complete, after filtration, distillation obtain product N, N-diethyl dichloro acetamide, the mol ratio of described diethylamine and dichloroacetyl chloride is 1:0.35;
(2), by N, N-diethyl dichloro acetamide, dry anhydrous potassium fluoride and tetramethylene sulfone mix, 130 ℃ of reaction 7h, the treated product N that obtains, N-diethyl two monofluoroacetamides, described N, the mol ratio of N-diethyl dichloro acetamide, anhydrous potassium fluoride and tetramethylene sulfone is 1:2.5:1.2;
(3), by N, N-diethyl two monofluoroacetamides and 15wt% aqueous sodium hydroxide solution mix, and more than back flow reaction 4h, through acidifying, extraction, distillation, obtain difluoro acetic acid, productive rate 93.1%.
In those skilled in the art, obviously the invention is not restricted to the details of above-mentioned one exemplary embodiment, and in the situation that not deviating from spirit of the present invention or essential characteristic, can realize the present invention with other specific form.Therefore, no matter from which point, all should regard embodiment as exemplary, and be nonrestrictive, scope of the present invention is limited by claims rather than above-mentioned explanation, is therefore intended to include in the present invention dropping on the implication that is equal to important document of claim and all changes in scope.
In addition, be to be understood that, although this specification sheets is described according to embodiment, but not each embodiment only comprises an independently technical scheme, this narrating mode of specification sheets is only for clarity sake, those skilled in the art should make specification sheets as a whole, and the technical scheme in each embodiment also can, through appropriately combined, form other embodiments that it will be appreciated by those skilled in the art that.
Claims (5)
1. a synthetic method for difluoro acetic acid, is characterized in that, comprises the steps:
Diethylamine and organic solvent are added in reaction unit, mix, control 10 ~ 20 ℃ of temperature of reaction, in 2h, slowly splash into dichloroacetyl chloride, react complete, after filtration, distillation obtain product N, N-diethyl dichloro acetamide, the mol ratio of described diethylamine and dichloroacetyl chloride is 1:0.3 ~ 0.4;
By N, N-diethyl dichloro acetamide, dry anhydrous potassium fluoride or Sodium Fluoride and tetramethylene sulfone mix, 120 ~ 140 ℃ of reaction 6 ~ 8h, the treated product N that obtains, N-diethyl two monofluoroacetamides, described N, the mol ratio of N-diethyl dichloro acetamide, anhydrous potassium fluoride or Sodium Fluoride and tetramethylene sulfone is 1:2 ~ 3:1 ~ 1.5;
By N, N-diethyl two monofluoroacetamides and 10 ~ 20wt% sodium hydroxide or potassium hydroxide aqueous solution mix, and more than back flow reaction 4h, through acidifying, extraction, distillation, obtain difluoro acetic acid.
2. the synthetic method of difluoro acetic acid according to claim 1, is characterized in that: in step (1), described organic solvent is benzene or toluene.
3. the synthetic method of difluoro acetic acid according to claim 1, is characterized in that: in step (1), the mol ratio of described diethylamine and dichloroacetyl chloride is 1:0.35.
4. the synthetic method of difluoro acetic acid according to claim 1, is characterized in that: in step (2), by N, N-diethyl dichloro acetamide, dry anhydrous potassium fluoride or Sodium Fluoride and tetramethylene sulfone mix, 130 ℃ of reaction 7h.
5. the synthetic method of difluoro acetic acid according to claim 1, is characterized in that: in step (2), and described N, the mol ratio of N-diethyl dichloro acetamide, anhydrous potassium fluoride or Sodium Fluoride and tetramethylene sulfone is 1:2.5:1.2.
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| CN201410316051.5A CN104072357A (en) | 2014-07-04 | 2014-07-04 | Synthetic method for difluoroethanoic acid |
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| CN201410316051.5A CN104072357A (en) | 2014-07-04 | 2014-07-04 | Synthetic method for difluoroethanoic acid |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107628939A (en) * | 2017-09-30 | 2018-01-26 | 湖北龙翔药业科技股份有限公司 | A kind of synthetic method of 2,3,3,3 tetrafluoro propionic acid |
| CN111056966A (en) * | 2018-12-28 | 2020-04-24 | 济宁康德瑞化工科技有限公司 | Preparation method of 2, 2-difluoroacetamide derivative |
| CN113582868A (en) * | 2021-08-19 | 2021-11-02 | 四川福思达生物技术开发有限责任公司 | Synthesis process of dichloroacetyldialkylamine |
| CN113636926A (en) * | 2021-08-19 | 2021-11-12 | 四川福思达生物技术开发有限责任公司 | Synthesis process of difluoroacetic acid |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06228043A (en) * | 1993-02-05 | 1994-08-16 | Asahi Glass Co Ltd | Production of difluoroacetic acid |
-
2014
- 2014-07-04 CN CN201410316051.5A patent/CN104072357A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06228043A (en) * | 1993-02-05 | 1994-08-16 | Asahi Glass Co Ltd | Production of difluoroacetic acid |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107628939A (en) * | 2017-09-30 | 2018-01-26 | 湖北龙翔药业科技股份有限公司 | A kind of synthetic method of 2,3,3,3 tetrafluoro propionic acid |
| CN111056966A (en) * | 2018-12-28 | 2020-04-24 | 济宁康德瑞化工科技有限公司 | Preparation method of 2, 2-difluoroacetamide derivative |
| CN111056966B (en) * | 2018-12-28 | 2022-09-02 | 济宁康德瑞化工科技有限公司 | Preparation method of 2, 2-difluoroacetamide derivative |
| CN113582868A (en) * | 2021-08-19 | 2021-11-02 | 四川福思达生物技术开发有限责任公司 | Synthesis process of dichloroacetyldialkylamine |
| CN113636926A (en) * | 2021-08-19 | 2021-11-12 | 四川福思达生物技术开发有限责任公司 | Synthesis process of difluoroacetic acid |
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