CN113233974A - Synthesis method of acyl fluoride - Google Patents
Synthesis method of acyl fluoride Download PDFInfo
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- CN113233974A CN113233974A CN202110387942.XA CN202110387942A CN113233974A CN 113233974 A CN113233974 A CN 113233974A CN 202110387942 A CN202110387942 A CN 202110387942A CN 113233974 A CN113233974 A CN 113233974A
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- fluoride
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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
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
Abstract
The invention belongs to the technical field of organic compound synthesis, and relates to a synthesis method of acyl fluoride. The synthesis process of acyl fluoride includes the reaction of carboxylic acid trifluoro methyl sulfide as material and negative monovalent fluoride salt to synthesize acyl fluoride. The synthesis method of acyl fluoride provided by the invention has the advantages of rapid reaction, mild reaction conditions, simple operation and environmental protection.
Description
Technical Field
The invention belongs to the technical field of organic compound synthesis, and relates to a synthesis method of acyl fluoride.
Background
Fluorine atoms have an important role in modern drug design and synthesis (Liu X, Xu C, Wang M, et al. Trifluoromethyltrimethylsilanes: nucleo if & beyond [ J ]. Chem Rev,2015,115(2):683 730.), and statistically, 15% to 20% of modern drugs contain fluorine-containing groups (HuiR, Zhang S, TanZ, et al. research protocol of Trifluoromethylation with Sodium triflate [ J ]. Chin J Org Chem (organic chemistry), 2017,37 (12): 3060 3075). The presence of fluorine-containing groups helps to increase the lipophilicity and metabolic stability of drug molecules (Yang B, Xu XH, Qi FL. cope-mediated chemical 1,2-bis (fluorination) of drugs with sodium trifluoromethane and sodium fluoromethane, and also reduces the development of drug resistance.
Acyl fluorides have the following advantages over other acyl compounds, such as acyl chlorides:
1. better stability, which makes acyl fluorides easier to store than acyl chlorides and less prone to rapid degradation due to moisture in the air;
2. the reaction activity is lower, so that the reaction using acyl fluoride as an acylation reaction reagent has better compatibility and can be compatible with more active groups;
3. can be used as a novel fluorinating reagent to participate in the reaction (Angew. chem. int. Ed.10.1002/anie.201902805).
Therefore, the development of a novel method for synthesizing the acyl fluoride realizes the mild and rapid preparation of the acyl fluoride, and has important significance for further research and application popularization of the compounds.
Disclosure of Invention
The invention aims to provide a novel efficient synthesis method of acyl fluoride aiming at the defects of the existing synthesis method, and the method has the advantages of quick reaction, low cost, mild conditions, simple synthesis process and the like.
In order to achieve the purpose, the invention adopts the technical scheme that: the synthesis process of acyl fluoride includes the reaction of carboxylic acid trifluoro methyl sulfide as material and negative monovalent fluoride salt to synthesize acyl fluoride.
In a preferred embodiment of the present invention, the reaction equation for synthesizing acyl fluoride is:
in the formulas (1) and (2), R is aryl, alkyl, alkenyl or alkynyl;
the synthesis process of the compound shown in the formula (1) comprises the following steps: dissolving a compound shown as a formula (2) and monovalent fluoride ion salt in a solvent, reacting for a certain time at a specific temperature to generate a compound shown as a formula (1);
the monovalent fluoride salt is any one or more salts containing monovalent fluoride ions, including inorganic salts and organic salts;
the solvent is an organic solvent and does not contain hydroxyl;
in the reaction system, the molar ratio of the compound shown in the formula (2) to the univalent fluoride salt is 1 (1-10);
the reaction temperature is-10 ℃ to 50 ℃, and the reaction time is 0.2 to 72 hours.
Further preferably, the reaction system contains an additive, and the reaction equation is as follows:
the additive is any one of phase transfer catalysts, and comprises polyether, cyclic crown ether, cyclic aza crown ether, quaternary ammonium salt, quaternary phosphonium salt, quaternary ammonium base and tertiary amine;
further preferably, the solvent is any one of 1, 2-dichloroethane, dichloromethane, acetonitrile, 1, 4-dioxane, benzene, toluene, xylene, trifluorotoluene, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, tetrahydrofuran, and diethyl ether.
Compared with the existing synthesis method, the synthesis method of acyl fluoride (I) has the following beneficial effects:
(1) the raw material carboxylic acid trifluoro-methyl-thionate compound adopted by the invention is easy to synthesize and store;
(2) the synthesis method has mild conditions, can be carried out in the air atmosphere at normal temperature and normal pressure, and has low requirement on required equipment;
(3) the operation is simple, convenient and safe, the waste is less, and the environment is protected;
(4) the reaction is rapid, and the compound is suitable for rapidly obtaining the compound.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1: in this example, silver fluoride was reacted with trifluoromethyl dodecanoate (S- (trifluoromethyl) dodecanoate) to synthesize acyl fluoride 1 a:
the reaction equation is:
the synthesis steps and the process are as follows: silver fluoride (2.5mmol,317.5mg), trifluromethyl dodecanoate (2.0mmol, 568mg) and 4.0mL of 1.4-dioxane were added to a 10mL reaction tube equipped with a magnetic stirrer; fixing the reaction tube on a magnetic stirrer, reacting at room temperature for 18 hours, separating and purifying to obtain the target product acyl fluoride 1a with the yield of 67.2%.
Example 2: in this example, the acyl fluoride 1b was synthesized by reacting silver fluoride with p-trifluoromethylbenzoic acid trifluoromethylthioester (S- (trifluoromethyl)4- (trifluoromethyl) thionate):
the reaction equation is:
the synthesis steps and the process are as follows: adding silver fluoride (1.0mmol,127mg) and p-trifluoromethylbenzoic acid trifluoromethylthioester (1.0mmol, 274mg) into a 10mL reaction tube provided with a magnetic stirrer, then adding 3.0mL acetonitrile, fixing the reaction tube on the magnetic stirrer, reacting for 36 hours at 15 ℃, and separating and purifying to obtain the target product acyl fluoride 1b with the yield of 71.3%.
Example 3: in this example, potassium fluoride was reacted with p-benzyltrifluoromethane thioester (S- (trifluoromethyl) [1,1' -biphenyl ] -4-carbothioate) to synthesize acyl fluoride 1 c:
the reaction equation is:
the synthesis steps and the process are as follows: adding potassium fluoride (1.8mmol,104.4mg), 18-crown-6 (1.8mmol,475.2mg) and p-phenylbenzoic acid trifluoromethyl thioester (1.0mmol, 282mg) into a 10mL reaction tube provided with a magnetic stirrer, adding 4.0mL dimethyl sulfoxide, fixing the reaction tube on the magnetic stirrer, reacting for 24 hours under 35 ℃ oil bath, separating and purifying to obtain the target product acyl fluoride 1c, wherein the yield is 65.5%.
Claims (4)
1. The synthesis method of acyl fluoride is characterized in that carboxylic acid trifluoromethyl sulfide is used as a raw material to react with monovalent negative fluoride salt to synthesize the acyl fluoride.
2. The method of synthesizing acyl fluoride according to claim 1, wherein the reaction equation is:
in the formulas (1) and (2), R is aryl, alkyl, alkenyl or alkynyl;
the synthesis process of the compound shown in the formula (1) comprises the following steps: dissolving a compound shown as a formula (2) and monovalent fluoride ion salt in a solvent, reacting for a certain time at a specific temperature to generate a compound shown as a formula (1);
the monovalent fluoride salt is any one or more salts containing monovalent fluoride ions, including inorganic salts and organic salts;
the solvent is an organic solvent and does not contain hydroxyl;
in the reaction system, the molar ratio of the compound shown in the formula (2) to the univalent fluoride salt is 1 (1-10);
the reaction temperature is-10 ℃ to 50 ℃, and the reaction time is 0.2 to 72 hours.
3. The method for synthesizing acyl fluoride according to claim 2, wherein the reaction system may contain additives, and the reaction equation is:
the additive is any one of phase transfer catalysts, and comprises polyether, cyclic crown ether, cyclic aza crown ether, quaternary ammonium salt and quaternary phosphonium salt.
4. The method for synthesizing acyl fluoride according to any one of claims 2 to 3, wherein the solvent is any one of 1, 2-dichloroethane, dichloromethane, acetonitrile, 1, 4-dioxane, benzene, toluene, xylene, trifluorotoluene, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, tetrahydrofuran, and diethyl ether.
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| CN202110387942.XA CN113233974A (en) | 2021-04-09 | 2021-04-09 | Synthesis method of acyl fluoride |
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| CN202110387942.XA CN113233974A (en) | 2021-04-09 | 2021-04-09 | Synthesis method of acyl fluoride |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114773185A (en) * | 2022-05-10 | 2022-07-22 | 南京理工大学 | Method for synthesizing benzoyl fluoride compound by using sodium trifluoromethanesulphinate |
| WO2022179448A1 (en) * | 2021-02-25 | 2022-09-01 | 山东领海生物科技有限公司 | Method for synthesizing silver (i) trifluoromethane thiolate |
| CN115925554A (en) * | 2022-12-05 | 2023-04-07 | 领海科技(青岛)有限公司 | Synthesis method of N-trifluoromethyl amine |
Citations (4)
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| WO1995025082A1 (en) * | 1994-03-15 | 1995-09-21 | Minnesota Mining And Manufacturing Company | Process for converting perfluorinated esters to perfluorinated acyl fluorides and/or ketones |
| CN1239940A (en) * | 1996-11-01 | 1999-12-29 | 美国3M公司 | Alpha-branched fluoroalkylcarbonyl fluorides and their derivatives |
| CN104583183A (en) * | 2012-07-24 | 2015-04-29 | 美国陶氏益农公司 | Fluoropicolinoyl fluorides and processes for their preparation |
| CN112778173A (en) * | 2021-02-25 | 2021-05-11 | 山东领海生物科技有限公司 | Synthesis method of silver (I) trifluoromethanesulfonate |
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2021
- 2021-04-09 CN CN202110387942.XA patent/CN113233974A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995025082A1 (en) * | 1994-03-15 | 1995-09-21 | Minnesota Mining And Manufacturing Company | Process for converting perfluorinated esters to perfluorinated acyl fluorides and/or ketones |
| CN1239940A (en) * | 1996-11-01 | 1999-12-29 | 美国3M公司 | Alpha-branched fluoroalkylcarbonyl fluorides and their derivatives |
| CN104583183A (en) * | 2012-07-24 | 2015-04-29 | 美国陶氏益农公司 | Fluoropicolinoyl fluorides and processes for their preparation |
| CN112778173A (en) * | 2021-02-25 | 2021-05-11 | 山东领海生物科技有限公司 | Synthesis method of silver (I) trifluoromethanesulfonate |
Non-Patent Citations (1)
| Title |
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| M. KREMLEV ETC.: ""S-Trifluoromethyl esters of thiocarboxylic acids, RC(O)SCF3"", 《TETRAHEDRON LETTERS》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022179448A1 (en) * | 2021-02-25 | 2022-09-01 | 山东领海生物科技有限公司 | Method for synthesizing silver (i) trifluoromethane thiolate |
| CN114773185A (en) * | 2022-05-10 | 2022-07-22 | 南京理工大学 | Method for synthesizing benzoyl fluoride compound by using sodium trifluoromethanesulphinate |
| CN114773185B (en) * | 2022-05-10 | 2023-01-03 | 南京理工大学 | Method for synthesizing benzoyl fluoride compound by utilizing sodium trifluoromethanesulphinate |
| CN115925554A (en) * | 2022-12-05 | 2023-04-07 | 领海科技(青岛)有限公司 | Synthesis method of N-trifluoromethyl amine |
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