WO2024000920A1 - 一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法 - Google Patents

一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法 Download PDF

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WO2024000920A1
WO2024000920A1 PCT/CN2022/124661 CN2022124661W WO2024000920A1 WO 2024000920 A1 WO2024000920 A1 WO 2024000920A1 CN 2022124661 W CN2022124661 W CN 2022124661W WO 2024000920 A1 WO2024000920 A1 WO 2024000920A1
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reaction
trifluoromethylenamine
compound
trifluoromethyl
enamine
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陈孝云
唐毅松
张晓彤
黄名扬
齐广杰
项欣然
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江苏科技大学
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B39/00—Halogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/12—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • the invention belongs to the technical field of synthesis of medicines, pesticide products and material intermediates. Specifically, it relates to a method using enamine and CF 3 SO 2 Na as raw materials, and using organic dye Na 2 -Eosin Y as a photosensitive catalyst under visible light irradiation.
  • Enamine is an unsaturated amine electron-rich compound containing a double bond in its structure and the carbon atom on the double bond is connected to a nitrogen atom. Because of its interesting redox properties, it can be regarded as a nitrogen-containing enol.
  • enamines are powerful intermediates in organic synthesis and are widely used in the synthesis of various organic heterocyclic molecules, including quinoline, pyridine, indole, pyrrole, etc., thus providing a series of alkaloids, peptides, etc. Or amino acids and their derivatives and other biologically active compounds or natural products provide precursors. Therefore, enamine compounds play an important role in the fields of medicine, biology and synthesis.
  • F is the element with the smallest radius and the strongest non-metallic property in the periodic table.
  • chemists have discovered that organic compounds containing fluorine have special physical and chemical properties that other compound molecules do not have.
  • fluorinated organic molecules exhibit excellent lipophilicity and occupy an important position in the field of organic chemical drug synthesis and research and development.
  • the introduction of CF3 groups can greatly affect the properties of organic molecules, thereby increasing their applicability as drugs, agricultural chemicals, or organic materials.
  • target groups are introduced into organic molecules through direct CHation of olefins catalyzed by visible light.
  • the present invention provides a method that uses easily prepared enamine as the raw material substrate, cheap and easily available CF 3 SO 2 Na as the trifluoromethyl source, and uses commercially available organic compounds in an air atmosphere and room temperature.
  • the dye Na 2 -Eosin Y was used as the catalyst, and tert-butyl hydroperoxide was used as the initiating additive.
  • the technical solution of the present invention is: a photocatalytic one-step method for preparing ⁇ -trifluoromethylenamine compounds based on an organic dye as a catalyst according to the present invention
  • R 1 or R 2 is any one of hydrogen, long-chain alkyl, cycloalkyl, benzyl, propynyl and their derivatives;
  • the EWG is any one of ester group, carbonyl group, amide group and derivative groups thereof;
  • Step 1 Place a polytetrafluoroethylene magnetic stirrer into a dry and clean quartz reaction tube with a stopper, and then add CF 3 SO 2 Na, Na 2 CO 3 and Na 2 -Eosin Y to the reaction tube in sequence. and solvent dimethyl sulfoxide; stir the reaction mixture at room temperature until it is evenly mixed, then add enamine to the mixture, and finally add tert-butyl hydroperoxide to the reaction mixture to prepare a reaction liquid;
  • Step 3 Quench the reaction solution in step (2) with deionized water, then transfer to a separatory funnel and extract with ethyl acetate. The combined organic phases are dried over anhydrous Na 2 SO 4 and then filtered. The filtrate is collected at the round bottom. In the flask, use a rotary evaporator to remove the solvent under reduced pressure to obtain a reaction mixture consisting mainly of crude trifluoromethylenamine derivatives, that is, a mixture of ⁇ -trifluoromethylenamine compounds and reaction by-products;
  • step (1) the shape of the polytetrafluoroethylene magnetic stirrer is spindle type, and its measurement unit size is 6*10mm; it stirs during the reaction, thereby speeding up the reaction and making the reaction complete. role in the reaction process and does not participate in the reaction itself.
  • the enamine is one of secondary amino acrylate or tertiary amino acrylate
  • the compound structure of the secondary amino acrylate ((E)-3-(secondary amino) acrylate compound) is any one of the following structures:
  • the compound structure of the tertiary amino acrylate ((E)-3-(tertiary amino) ethyl acrylate compound) is any one of the following structures:
  • the trifluoromethyl group is derived from Langlois reagent, that is, CF 3 SO 2 Na, and its structure is as follows:
  • the quartz tube is made of high-purity quartz powder, its silica content is more than 99.9%, and its hardness, light transmittance and high temperature resistance are better than those of ordinary glass reaction tubes. More excellent.
  • step (1) the dosage of Na 2 -Eosin Y is 10 mol%
  • reaction molar ratio of the enamine, CF 3 SO 2 Na, Na 2 CO 3 and tert-butyl hydroperoxide is 1:4:3:4;
  • the enamine is used as the reaction substrate, and the concentration in the solvent dimethyl sulfoxide is 0.1 mol/L;
  • the CF 3 SO 2 Na is used as the reaction trifluoromethyl source, and the concentration in the solvent dimethyl sulfoxide is 0.4 mol/L.
  • the Na 2 CO 3 is used as a reaction additive, and the concentration in the solvent dimethyl sulfoxide is 0.3 mol/L;
  • the tert-butyl hydroperoxide is used as a reaction initiator, and the concentration in the solvent dimethyl sulfoxide is 0.4 mol/L.
  • room temperature is: 18-33°C.
  • Enamine It is an unsaturated amine electron-rich compound that contains a double bond in its structure and the carbon atom on the double bond is connected to a nitrogen atom. Because its structure contains a carbon-carbon double bond activated by a nitrogen atom and a Nucleophilic amino group, therefore has many excellent reaction characteristics, such as (1) carbon-carbon double bonds are activated by nitrogen atoms, which greatly improves the activity of carbon-carbon double bond reactions in enamines, and can be used to prepare various chiral amines and Multi-substituted natural amine derivatives; (2) having multiple nucleophilic or electrophilic centers; (3) in the enamine structure, if the group substituted on one end of the carbon-carbon double bond is an active group, such as : Halogen, boron-based, phosphine-based, silicon-based, etc.
  • enamines have many advantages such as high reactivity and many reaction sites, enamines can be used as powerful intermediates in organic synthesis, especially in the synthesis of natural products and nitrogen-containing heterocyclic compounds such as Quinoline, pyridine, indole, pyrrole, etc. are widely used in the synthesis, thus providing a series of biologically active compounds such as alkaloids, peptides or amino acids and their derivatives, or providing precursors for natural products.
  • enamines themselves also have special medicinal properties and exist as key structural units in countless natural products and drugs.
  • enamine compounds are of great significance in the fields of medicine, biology and synthesis.
  • CF 3 SO 2 Na Sodium trifluoromethylsulfinate
  • This reagent was reported by Langlois et al. in 1991 and was used as a pro- Electroreagents are used in research on trifluoromethylation of aromatic compounds.
  • CF 3 SO 2 Na is more stable, economical, and easy to operate.
  • it has often been used as a trifluoromethyl source to introduce trifluoromethyl into target compounds. It has been widely used in the field of synthetic organic fluorine chemistry.
  • Eosin Y disodium salt (Na 2 -Eosin Y): It is a red fluorescent dye, also known as eosin Y disodium salt. It dissociates into negatively charged anions in water and can bind to the amino groups of proteins. The combination of positively charged cations stains the cytoplasm, red blood cells, collagen, muscle fibers, connective tissue, eosinophilic granules, etc. in varying degrees of red or pink. As an acid dye, it is often used in hematoxylin-eosin stain staining and as a counterstain for hematoxylin. The staining makes the cytoplasm appear pink-orange, and the nucleus appears dark blue or deep purple.
  • Eosin Y disodium salt can also be combined with Azure II for staining for morphological observation of bone marrow cells.
  • Azure A/eosin Y staining can reveal cell granules, microorganisms and nucleoli, as well as insect muscle tissue and cells infected with mosquito iridovirus.
  • Dimethyl sulfoxide It is a sulfur-containing organic compound with the molecular formula C 2 H 6 OS. It is a colorless, odorless, transparent, hygroscopic, flammable liquid at room temperature. It has the characteristics of high polarity, high boiling point, good thermal stability, aprotic, and miscible with water. It can be dissolved in most organic substances such as ethanol, propanol, benzene and chloroform, and is known as the "universal solvent". Heating in the presence of acid will produce small amounts of methyl mercaptan, formaldehyde, dimethyl sulfide, methanesulfonic acid and other compounds.
  • It has decomposition phenomenon at high temperatures, reacts violently with chlorine, and burns in the air with a light blue flame. It can be used as organic solvent, reaction medium and organic synthesis intermediate. It can also be used as a dyeing solvent, dye remover, dyeing carrier for synthetic fibers, and an absorbent for recovering acetylene and sulfur dioxide.
  • Tert-butyl hydroperoxide It is an important branch of organic peroxides. This substance is a volatile, yellowish transparent liquid. It is an alkyl hydrogen organic peroxide, also known as the third Butyl hydroperoxide. Tert-butyl hydroperoxide is slightly soluble in water and easily soluble in most organic solvents such as alcohol and ether and sodium hydroxide aqueous solution. Its solubility in water is 12% and it is slightly acidic. It is stable below 75°C, loses oxygen at 95°C-100°C, and explodes at 250°C.
  • Mainly used as initiator for polymerization reactions (such as polyvinyl chloride, polyacrylic acid emulsion polymerization monomers, etc.), cross-linking agent for unsaturated polyester, emulsion polymerization, vulcanization of natural rubber, diesel additives, and paint industry wait. It is also widely used as a raw material for the synthesis of other organic peroxides.
  • Sodium carbonate (Na 2 CO 3 ) It is an inorganic compound with the chemical formula Na 2 CO 3 . It is also called soda ash, soda, and soda ash. It is a white, odorless powder or granule at room temperature. It is water-absorbent, easily soluble in water and glycerin, slightly soluble in absolute ethanol, and insoluble in propanol. Its aqueous solution is alkaline and corrosive to a certain extent, and can undergo metathesis reactions with acids, as well as with some calcium salts and barium salts. The solution is alkaline and can turn phenolphthalein red. It is also an important inorganic chemical raw material, mainly used in the production of flat glass, glass products and ceramic glazes. It is also widely used in daily washing, acid neutralization and food processing.
  • the beneficial effects of the present invention are: (1)
  • the method of the present invention utilizes green and environmentally friendly visible light irradiation, economical, stable and easy-to-operate CF 3 SO 2 Na as the trifluoromethyl source, and the commercially available organic dye Na 2 -Eosin Y is used as a catalyst to catalyze the two-component reaction of enamine and CF 3 SO 2 Na to efficiently and quickly prepare ⁇ -trifluoromethyl enamine compound, which is a derivative intermediate with medicinal value.
  • the method of the present invention is simple to operate, the experimental device is easy to assemble and easy to automate, and the substrates and raw materials used are widely available, cheap and easy to obtain; the reaction conditions are mild, green, insensitive to air and water, and avoid flammability
  • the synthesized ⁇ -CF 3- substituted enamine is a potential ⁇ -amino acid precursor. This makes ⁇ -trifluoromethylenamine compounds have greater practical potential in the field of further organic synthesis research in the later stage.
  • Figure 1 is a structural flow chart of the present invention.
  • R 1 or R 2 is any one of hydrogen, long-chain alkyl, cycloalkyl, benzyl, propynyl and their derivatives;
  • the EWG is any one of ester group, carbonyl group, amide group and its derivative groups
  • Step 1 Place a polytetrafluoroethylene magnetic stirrer into a dry and clean quartz reaction tube with a stopper, and then add sodium trifluoromethanesulfinate CF 3 SO 2 Na and Na 2 CO to the reaction tube in sequence. 3. Na 2 -Eosin Y and solvent dimethyl sulfoxide; stir the reaction mixture at room temperature until it is evenly mixed, then add enamine to the mixture, and finally add tert-butyl hydroperoxide to the reaction mixture. Prepare reaction solution;
  • Step 3 Quench the reaction solution in step (2) with deionized water, then transfer to a separatory funnel and extract with ethyl acetate. The combined organic phases are dried over anhydrous Na 2 CO 3 and then filtered. The filtrate is collected at the round bottom.
  • a rotary evaporator to remove the solvent under reduced pressure to prepare a reaction mixture mainly composed of trifluoromethylenamine derivatives, that is, a mixture of ⁇ -trifluoromethylenamine compounds and reaction by-products;
  • the Langlois reagent a source reagent of trifluoromethyl, is CF 3 SO 2 Na, and its structure is as follows:
  • step (1) the shape of the polytetrafluoroethylene magnetic stirrer is spindle type, and its measurement unit size is 6*10mm; it stirs during the reaction, thereby speeding up the reaction and making the reaction complete. role in the reaction process and does not participate in the reaction itself.
  • the quartz tube is made of high-purity quartz powder, with a silicon dioxide content of more than 99.9%. Its hardness, light transmittance and high temperature resistance are all better than ordinary glass reaction tubes.
  • step (1) the enamine is one of secondary amino acrylate or tertiary amino acrylate
  • the compound structure of the secondary amino acrylate ((E)-3-(secondary amino) acrylate compound) is any one of the following structures:
  • the compound structure of the tertiary amino acrylate ((E)-3-(tertiary amino) ethyl acrylate compound) is any one of the following structures:
  • the Na 2 -Eosin Y is used as a catalyst, and the dosage is 10 mol%;
  • reaction molar ratio of the enamine, CF 3 SO 2 Na, Na 2 CO 3 and tert-butyl hydroperoxide is 1:4:3:4;
  • the enamine is used as the reaction substrate, and the concentration in the solvent dimethyl sulfoxide is 0.1 mol/L;
  • the CF 3 SO 2 Na is used as the reaction trifluoromethyl source, and the concentration in the solvent dimethyl sulfoxide is 0.4 mol/L.
  • the Na 2 CO 3 is used as a reaction additive, and the concentration in the solvent dimethyl sulfoxide is 0.3 mol/L;
  • room temperature is: 18-33°C.
  • reaction mixture containing (E)-3-(sec-butylamino)-2-(trifluoromethyl)ethyl acrylate compound was separated and purified using a 300 mesh silica gel chromatography column, using V petroleum ether : V ethyl acetate.
  • reaction mixture was quenched with deionized water, then transferred to a separatory funnel and extracted with ethyl acetate.
  • the organic phases were combined, dried over anhydrous Na 2 SO 4 and then filtered.
  • the filtrate was collected in a round-bottomed flask and removed under reduced pressure using a rotary evaporator.
  • Ethyl acetate thereby obtaining a reaction mixture mainly composed of (E)-3-(tertiary amino)-2-(trifluoromethyl)acrylate derivatives, namely (E)-3-(dibenzylamino) )-2-(trifluoromethyl)ethyl acrylate compound and a mixture of reaction by-products;
  • reaction mixture containing (E)-3-(dibenzylamino)-2-(trifluoromethyl)ethyl acrylate compound was separated and purified using a 300 mesh silica gel chromatography column, and the mixture was separated into V petroleum ether : V ethyl acetate.
  • reaction mixture containing (E)-3-(dipropylamino)-2-(trifluoromethyl)ethyl acrylate compound was separated and purified using a 300 mesh silica gel chromatography column, and then V petroleum ether : V ethyl acetate was used.
  • Ester : V triethylamine 16:1:0.5 is used as the eluent to pass through the column, and the solution containing the pure (E)-3-(dipropylamino)-2-(trifluoromethyl)acrylic acid ethyl ester compound is collected.
  • reaction was quenched with deionized water, then transferred to a separatory funnel and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous Na 2 SO 4 and then filtered. The filtrate was collected in a round-bottomed flask and the ethyl acetate was removed under reduced pressure using a rotary evaporator. ester, thereby obtaining a reaction mixture mainly composed of (E)-3-(tertiary amino)-2-(trifluoromethyl)acrylate derivatives, namely (tetrahydrofuran-2-yl)methyl(E)- A mixture of 3-(dipropylamino)-2-(trifluoromethyl)acrylate compound and reaction by-products;
  • reaction mixture containing 2-chlorobenzyl (E)-3-(dipropylamino)-2-(trifluoromethyl)acrylate compound was separated and purified using a 300 mesh silica gel chromatography column, and then V petroleum ether was used.
  • reaction was quenched with deionized water, then transferred to a separatory funnel and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous Na 2 SO 4 and then filtered. The filtrate was collected in a round-bottomed flask and acetic acid was removed under reduced pressure using a rotary evaporator. ethyl ester, thereby obtaining a reaction mixture mainly composed of (E)-3-(tertiary amino)-2-(trifluoromethyl)acrylate derivative, namely (E)-3-(dipropylamino)- A mixture of 2-(trifluoromethyl)phenyl acrylate compound and reaction by-products;
  • reaction mixture containing (E)-3-(dipropylamino)-2-(trifluoromethyl)phenyl acrylate was separated and purified using a 300 mesh silica gel chromatography column, and then V petroleum ether :V ethyl acetate was used.
  • the enamine substrates implemented in the present invention are not limited to the amine source being aliphatic chain ammonia, benzyl amine, and propargyl amine.
  • the ammonia source is tetrahydropyrrole, morpholine, tetrahydropyridine, and those with substitutions at different positions.
  • the reaction can still proceed smoothly and the target product can be given in a higher yield.
  • the substituent group ester part is not limited to alkyl ester and benzyl ester. When carbonyl group and amide are substituent groups, these compounds can still be suitable as the substrate of the reaction and make people happy. Satisfactory yield gives the target product.

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Abstract

本发明公开了一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法。属于医药、农药产品及材料中间体合成技术领域；所述β-三氟甲基烯胺化合物的结构如式(I)所示：本发明所述的制备方法是在环保绿色且经济的可见光照射下，以催化量的商业化有机染料Na 2-Eosin Y为光催化剂，同时以廉价易得、稳定且操作简便的CF 3SO 2Na为三氟甲基源，Na 2CO 3为添加剂，叔丁基过氧化氢为引发剂。该反应条件温和，对空气和水不敏感、操作简便、反应效率高且目标产物易于纯化。同时，本发明具有广泛的反应底物范围和良好的官能团耐受性，并且多数目标产品化合物能以良好至优异的收率获得。

Description

一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法 技术领域
本发明属于医药、农药产品及材料中间体合成技术领域，具体的涉及一种以烯胺和CF 3SO 2Na为原料，在可见光照射下，以有机染料Na 2-Eosin Y为光敏催化剂，通过烯胺和CF 3SO 2Na两组分直接C-H三氟甲基化一步法制备β-三氟甲基烯胺化合物的方法。
背景技术
烯胺是一种结构上含双键且双键上的碳原子与氮原子相连的不饱和胺类富电子化合物，因其具有有趣的氧化还原特性，故可看作是含氮的烯醇。此外，烯胺是有机合成当中有力的中间体，被广泛的运用到各类有机杂环分子的合成中，包括喹啉、吡啶、吲哚、吡咯等，从而提供了一系列如生物碱、肽或氨基酸以及它们的衍生物等具有生物活性的化合物或者是天然产物提供了前体。因此，烯胺类化合物在医药、生物及合成领域当中发挥着重要的作用。随着有机合成工作者对烯胺类物质的深入研究，该化合物的合成方法日益成熟，涌现出了一批简单可靠的合成方式，例如Nair’s烯胺合成、Maurya's烯胺合成、Chen’s烯胺合成等。现如今，国内外有机化学工作者们通过不断的努力，除了在新的烯胺合成路线方法上大胆尝试外，在更加广泛的领域内，对烯胺的运用同样在不断推陈出新。
众所周知，F是元素周期表中半径较小且非金属性最强的元素，随着科学技术的发展，化学家们发现含有氟元素的有机化合物具有其他化合物分子不具备的特殊物理化学性质，与非氟化的有机分子相比而言，含氟有机分子则展现出了极好的亲脂性，在有机化学药物合成研发领域占有重要的地位。其中CF 3基团的引入可以极大地影响有机分子的性质，从而增加它们作为药物、农用化学品或有机材料的适用性，目前，通过可见光催化的烯烃直接C-H化反应将目标基团引入到有机分子中成为有机合成的重要手段之一，而CF 3成功的引入能够显著的改善化合物在亲脂性、酸性、吸附或吸收性、以及化合物的代谢稳定性方面起到了关键的作用。因此，含有CF 3的有机化合物在医药、材料以及农药等领域应用极为广泛，近些年，以更为绿色环保且廉价的方式向目标有机化合物中引入CF 3成为越来越多的化学科研工作者们需要解决的问题之一。
目前，通过烯烃直接C-H官能化将CF 3成功地引入不同的目标有机分子中已经建立起许多可靠的方法，例如在铜的催化下，使用不同的三氟甲基来源的试剂(Togni试剂、Umemoto试剂和TMSCF 3)进行烯烃的C-H三氟甲基化反应，但所得到的目标产物未能构建烯烃的C-CF 3键。在此之后，一种使用CF 3I作为三氟甲基源，在可见光诱导下实现了末端烯烃的三氟甲基化。最近，一种无过渡 金属催化的烯胺C-H三氟甲基化反应，将三氟甲基成功引入烯胺双键得以实现。上述工作都成功的构建了C-CF 3键,在一定程度上开创了烯烃三氟甲基化领域新的舞台，然而，这些方法当中，所使用的三氟甲基化试剂成本高、稳定性差；或以昂贵的过渡金属作为催化剂；有的方法需要额外加热供能从而启动反应进行；从绿色环保以及经济角度看并不可取。因此，开发一种更为温和且绿色环保的方法将CF 3引入烯胺的化合物仍是一项有意义的工作。
发明内容
针对上述问题，本发明提供了一种在空气氛、室温下，以易制备的烯胺为原料底物，廉价易得的CF 3SO 2Na为三氟甲基来源，且以市售的有机染料Na 2-Eosin Y为催化剂，叔丁基过氧化氢为引发添加剂，在白色LEDs(λ max＝455nm)灯照射下，成功实现了烯胺和三CF 3SO 2Na两组分直接烯烃的C-H三氟甲基化一步法制备β-三氟甲基烯胺化合物的温和绿色方法。
本发明的技术方案是：本发明所述的一种基于有机染料作为催化剂的光催化一步法制备β-三氟甲基烯胺化合物的方法；
所述的β-三氟甲基烯胺化合物的化学结构如式I所示：
Figure PCTCN2022124661-appb-000001
其中，所述R 1或R 2为氢、长链烷基、环烷基、苄基、丙炔基及其衍生基团中的任意一种；
所述EWG为酯基、羰基、酰胺及其衍生基团中的任意一种；
其具体步骤包括如下：
步骤1、在干燥洁净的、带有塞子的石英反应管中放入聚四氟乙烯磁力搅拌子，随后依次向该反应管中加入CF 3SO 2Na、Na 2CO 3、Na 2-Eosin Y和溶剂二甲基亚砜；室温下搅拌反应混合物使其混合均匀后，再向该混合物中加入烯胺，最后向该反应混合液中加入叔丁基过氧化氢，制得反应液；
步骤2、在空气氛、室温下，将制得的反应液在10W白色LEDs(λmax＝455nm)灯照射下搅拌反应12小时。通过TLC板监测反应，待反应烯胺原料消耗直至消失后，停止反应；
步骤3、将步骤(2)中的反应液用去离子水淬灭，之后转移至分液漏斗并用乙酸乙酯萃取，合并有机相通过无水Na 2SO 4干燥之后过滤，滤液收集至圆底烧瓶中，使用旋转蒸发仪减压除去溶剂,从而得到粗产物三氟甲基烯胺类衍生物为主的反应混合物，即β-三氟甲基烯胺化合物及反应副产物的混合物；
步骤4、将制得的β-三氟甲基烯胺化合物及反应副产物的混合物用300目硅胶色谱柱进行分离纯化，用V 石油醚：V 乙酸乙酯：V 三乙胺＝16:1:0.5为洗脱剂，收集含有纯β-三氟甲基烯胺类衍生物的溶液并转移收集至圆底烧瓶中，用旋转蒸发仪除去洗脱剂，即石油醚、乙酸乙酯和三乙胺的混合物；随后，对其进行干燥并称重，最终得到浅黄色或黄色的油状或固体化合物，即为基于有机染料催化的β-三氟甲基烯胺化合物。
进一步的，在步骤(1)中，所述聚四氟乙烯磁力搅拌子的形状为纺锤型，其计量单位大小为6*10mm；在反应中起到搅拌从而能够加快反应进行并使得反应进行彻底的作用，在反应过程中并未参与反应本身。
进一步的，在步骤(1)中，所述烯胺是仲胺基丙烯酸酯或叔胺基丙烯酸酯中的一种；
即：原料(E)-3-(仲胺基)丙烯酸酯化合物、(E)-3-(叔胺基)丙烯酸乙酯化合物；
其中，所述仲胺基丙烯酸酯的化合物结构((E)-3-(仲胺基)丙烯酸酯化合物)为下列结构中的任意一种：
Figure PCTCN2022124661-appb-000002
所述叔胺基丙烯酸酯的化合物结构((E)-3-(叔胺基)丙烯酸乙酯化合物)为下列结构中的任意一种：
Figure PCTCN2022124661-appb-000003
进一步的，在步骤(1)中，所述三氟甲基来源于Langlois试剂，即CF 3SO 2Na，其结构如下：
Figure PCTCN2022124661-appb-000004
进一步的，在步骤(1)中，所述石英管是由高纯度的石英粉制成，其二氧化硅的含量在99.9％以上，硬度、透光度以及耐高温特性都比普通玻璃反应管更为优异。
进一步的，在步骤(1)中，所述Na 2-Eosin Y的用量为10mol％；
所述烯胺、CF 3SO 2Na、Na 2CO 3、叔丁基过氧化氢的反应摩尔比为1:4:3:4；
所述烯胺作为反应底物，在溶剂二甲基亚砜中的浓度为0.1mol/L；
所述CF 3SO 2Na作为反应三氟甲基源，在溶剂二甲基亚砜中的浓度为0.4mol/L。
所述Na 2CO 3作为反应添加剂，在溶剂二甲基亚砜中的浓度为0.3mol/L；
所述叔丁基过氧化氢作为反应引发剂，在溶剂二甲基亚砜中的浓度为0.4mol/L。
进一步的，所述室温是：18-33℃。
具体的，
1、烯胺：是一种结构上含双键且双键上的碳原子与氮原子相连的不饱和胺类富电子化合物，因其结构上含有一个被氮原子活化的碳碳双键和一个亲核氨基，因而具有诸多优异的反应特性，如(1)碳碳双键被氮原子活化，使得烯胺中碳碳双键反应的活性大大提高，从而可以用来制备各种手性胺和多取代的天然胺基衍生物；(2)具有多个亲核或者是亲电中心；(3)在烯胺结构中，若碳碳双键一端上所取代的基团是活性基团，如:卤素、硼基、膦基、硅基等。正因烯胺类物质具有反应活性高及反应位点多等诸多优点，故此烯胺可以作为在有机合成中一种强有力的中间体，特别是在天然产物的合成和含氮杂环化合物如喹啉、吡啶、吲哚、吡咯等的合成中具有广泛的应用，从而提供了一系列例如生物碱、肽或氨基酸以及它们的衍生物等具有生物活性的化合物或者是天然产物提供了前体。此外，烯胺自身也具有特殊药性，作为关键结构单元存在于无数天然产物和药物中。综上，烯胺类化合物在医药、生物及合成领域具有重要意义。
2、三氟甲基亚磺酸钠(CF 3SO 2Na)：一种市售常见的三氟甲基源试剂，该试剂是在1991年，Langlois等人报道了该物质并将其作为亲电试剂用于芳香族化合物的三氟甲基化的研究工作，与其他的三氟甲基源试剂(如Togni试剂、Umemoto试剂、TMSCF 3试剂、CF 3I试剂等)相比，CF 3SO 2Na具有更加稳定、经济、操作方便等特点，近些年，常常被用作为三氟甲基源将三氟甲基引入至目标化合物中，在合成有机氟化学领域有广泛的应用。
3、伊红Y二钠盐(Na 2-Eosin Y)：是一种红色荧光染料，又称作曙红Y二钠盐，在水中解离成带负电荷的阴离子，能够与蛋白质氨基中带正电荷的阳离子结合从而使细胞质，红细胞，胶原，肌纤维，结缔组织，嗜伊红颗粒等染成不同程度的红色或者粉红色。作为一种酸性染料，常用于苏木素-伊红染色法、苏木素的复染剂。染色使得细胞质呈粉红-橘黄色，细胞核显深蓝或深紫。伊红Y二钠盐也可与天青II结合染色用于骨髓细胞的形态学观察。天青A/伊红Y染色能显示细胞颗粒，微生物和核仁，也可显示昆虫肌肉组织以及蚊虹彩病毒感染的细 胞。
4、二甲基亚砜(DMSO)：是一种含硫有机化合物，分子式为C 2H 6OS，常温下为无色无臭透明且具有吸湿性的可燃液体。具有高极性、高沸点、热稳定性好、非质子、与水混溶的特性，能溶于乙醇、丙醇、苯和氯仿等大多数有机物，被誉为“万能溶剂”。在酸存在时加热会产生少量甲基硫醇、甲醛、二甲基硫、甲磺酸等化合物。此外，在高温下有分解现象，遇氯能发生剧烈反应,在空气中燃烧发出淡蓝色火焰。可作有机溶剂、反应介质和有机合成中间体。也可用作合成纤维的染色溶剂、去染剂、染色载体以及回收乙炔、二氧化硫的吸收剂。
5、叔丁基过氧化氢(TBHP)：是有机过氧化物的一个重要分支，该物质为挥发性、微黄色透明液体，是一种烷基氢有机过氧化物，又被称为第三丁基过氧化氢。叔丁基过氧化氢微溶于水，易溶于醇、醚等多数有机溶剂和氢氧化钠水溶液。在水中溶解度为12％，呈弱酸性。在75℃以下稳定，在95℃-100℃失去氧，250℃时则会爆炸。主要用作聚合反应(如聚氯乙烯、聚丙烯酸类乳液聚合单体后消除等)的引发剂、不饱合聚脂的交联剂、乳化聚合、天然生胶加硫、柴油添加剂、油漆行业等。亦广泛用作合成其他有机过氧化物的原料。
6、碳酸钠(Na 2CO 3)：是一种无机化合物，化学式为Na 2CO 3，又叫纯碱、苏打、碱灰。常温下为白色无气味的粉末或颗粒，有吸水性，易溶于水和甘油，微溶于无水乙醇，难溶于丙醇。其水溶液呈碱性且有一定的腐蚀性，能与酸发生复分解反应，也能与一些钙盐、钡盐发生复分解反应。溶液显碱性，可使酚酞变红。它还是一种重要的无机化工原料，主要用于平板玻璃、玻璃制品和陶瓷釉的生产。还广泛用于生活洗涤、酸类中和以及食品加工等。
本发明的有益效果是：(1)、本发明的方法利用绿色环保的可见光照射，经济、稳定且操作方便的CF 3SO 2Na作为三氟甲基源，市售易得的有机染料Na 2-Eosin Y作为催化剂催化的烯胺与CF 3SO 2Na两组分一步法反应，高效快速地制备出β-三氟甲基烯胺化合物，这是一种具有药用价值的衍生物中间体；(2)、本发明的方法操作简单、实验装置组装简便且易于自动化，使用的底物和原料来源广泛、廉价易得；反应条件温和、绿色，对空气和水不敏感，避免了易燃易爆高污染有机溶剂的使用；具有广泛的底物范围和良好的官能团耐受性，能够以高产率给出目标产物，合成的β-CF 3取代烯胺是潜在的β-氨基酸前体，使得β-三氟甲基烯胺化合物在后期进一步的有机合成研究领域中具有更加巨大实用潜力。
附图说明
图1是本发明的结构流程图。
具体实施方式
为了更清楚地说明本发明的技术方案，下面将对本发明中进行进一步的叙述；显而易见地，下面描述中的仅仅是一部分的实施例，对于本领域的普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些将本发明所述的技术方案应用于其它类似情景；为了更清楚地说明本发明的技术方案，下面结合附图对本发明的技术方案做进一步的详细说明：
如图所述；本发明所述的一种β-三氟甲基烯胺化合物，所述β-三氟甲基烯胺化合物的化学结构如式Ⅰ所示：
Figure PCTCN2022124661-appb-000005
在式Ⅰ中，所述R 1或R 2为氢、长链烷基、环烷基、苄基、丙炔基及其衍生基团中的任意一种；
所述EWG为酯基、羰基、酰胺及其衍生基团中的任意一种；
进一步的，一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法，具体操作步骤如下：
步骤1、在干燥洁净的、带有塞子的石英反应管中放入聚四氟乙烯磁力搅拌子，随后依次向该反应管中加入三氟甲亚磺酸钠CF 3SO 2Na、Na 2CO 3、Na 2-Eosin Y和溶剂二甲基亚砜；室温下搅拌反应混合物使其混合均匀后，再向该混合物中加入烯胺，最后向该反应混合液中加入叔丁基过氧化氢，制得反应液；
步骤2、在空气氛、室温下，将反应混合物在10W白色LEDs(λ max＝455nm)灯照射下搅拌反应12小时；通过TLC板监测反应，待反应烯胺原料消耗直至消失后，停止反应；
步骤3、将步骤(2)中的反应液用去离子水淬灭，之后转移至分液漏斗并用乙酸乙酯萃取，合并有机相通过无水Na 2CO 3干燥之后过滤，滤液收集至圆底烧瓶中，使用旋转蒸发仪减压除去溶剂，从而制得以三氟甲基烯胺类衍生物为主的反应混合物，即β-三氟甲基烯胺化合物及反应副产物的混合物；
步骤4、将得到的含有β-三氟甲基烯胺类衍生物的反应混合物用300目硅胶色谱柱进行分离纯化，用V 石油醚：V 乙酸乙酯：V 三乙胺＝16:1:0.5为洗脱剂，收集含有纯β-三氟甲基烯胺类衍生物的溶液并转移收集至圆底烧瓶中，用旋转蒸发仪除去洗脱剂，即石油醚、乙酸乙酯和三乙胺的混合物；随后，对纯化得到的β-三氟 甲基烯胺类衍生物进行干燥并称重，最终得到浅黄色或黄色的油状或固体β-三氟甲基烯胺化合物，即为基于有机染料催化的β-三氟甲基烯胺化合物。
进一步的，所述Langlois试剂，一种三氟甲基的来源试剂，即CF 3SO 2Na,其构如下：
Figure PCTCN2022124661-appb-000006
进一步的，在步骤(1)中，所述聚四氟乙烯磁力搅拌子的形状为纺锤型，其计量单位大小为6*10mm；在反应中起到搅拌从而能够加快反应进行并使得反应进行彻底的作用，在反应过程中并未参与反应本身。
进一步的，所述石英管是由高纯度的石英粉制成，其二氧化硅的含量在99.9％以上，硬度、透光度以及耐高温特性都比普通玻璃反应管更为优异。
在步骤(1)中，所述烯胺是仲胺基丙烯酸酯或叔胺基丙烯酸酯中的一种；
其中，所述仲胺基丙烯酸酯的化合物结构((E)-3-(仲胺基)丙烯酸酯化合物)为下列结构中的任意一种：
Figure PCTCN2022124661-appb-000007
所述叔胺基丙烯酸酯的化合物结构((E)-3-(叔胺基)丙烯酸乙酯化合物)为下列结构中的任意一种：
Figure PCTCN2022124661-appb-000008
进一步的，所述Na 2-Eosin Y作为催化剂，用量为10mol％；
所述烯胺、CF 3SO 2Na、Na 2CO 3、叔丁基过氧化氢的反应摩尔比为1:4:3:4；
所述烯胺作为反应底物，在溶剂二甲基亚砜中的浓度为0.1mol/L；
所述CF 3SO 2Na作为反应三氟甲基源，在溶剂二甲基亚砜中的浓度为0.4mol/L。
所述Na 2CO 3作为反应添加剂，在溶剂二甲基亚砜中的浓度为0.3mol/L；
进一步的，所述的室温是：18-33℃。
实施例1：
β-三氟甲基烯胺化合物
2-chlorobenzyl(E)-3-(benzylamino)-2-(trifluoromethyl)acrylate的合成：
Figure PCTCN2022124661-appb-000009
在干燥洁净的10mL石英管中加入聚四氟乙烯磁子，紧接着依次加入CF 3SO 2Na(312.1mg，2.0mmol)、Na 2CO 3(158.9mg，1.5mmol)、Na 2-Eosin Y(0.05mmol，10mol％)、溶剂二甲基亚砜(5.0mL)，搅拌混合均匀后再加入2-氯苄基(E)-3-(苄氨基)-2-(三氟甲基)丙烯酸酯(140.1mg，0.5mmol)，最后加入叔丁基过氧化氢(192.4μL，2.0mmol)，制得反应液；
在空气氛、室温下，将装有反应液的石英管置于10W白色LEDs(λ max＝455nm)灯照射下搅拌反应12小时并用TLC板监测反应，当反应中2-氯苄基(E)-3-(苄基氨基)丙烯酸酯原料消耗直至消失后停止反应；
反应用去离子水淬灭，之后转移至分液漏斗并用乙酸乙酯萃取，合并有机相，通过无水Na 2SO 4干燥之后过滤，滤液收集至圆底烧瓶，接着使用旋转蒸发仪减压除去乙酸乙酯，从而得到以(E)-3-(伯胺基)-2-(三氟甲基)丙烯酸酯类衍生物为主的反应混合物，即2-氯苄基(E)-3-(苄基氨基)-2-(三氟甲基)丙烯酸酯及反应副产物的混合物；
将得到的含有2-氯苄基(E)-3-(苄基氨基)-2-(三氟甲基)丙烯酸酯化合物的反应混合物用300目硅胶色谱柱乙酸乙酯分离纯化，以V 石油醚:V 乙酸乙酯:V 三乙胺＝16:1:0.5为洗脱剂进行过柱，将含有纯2-氯苄基(E)-3-(苄基氨基)-2-(三氟甲基)丙烯酸酯的溶液收集并转移至圆底烧瓶中，用旋转蒸发仪旋除去洗脱剂，即乙酸乙酯、石油醚和三乙胺的混合物，从而得到2-氯苄基(E)-3-(苄基氨基)-2-(三氟甲基)丙烯酸酯从纯品；随后，对其进行干燥并称重最终得到171.6mg黄色油状2-氯苄基(E)-3-(苄基氨基)-2-(三氟甲基)丙烯酸酯纯品，即为所述的一种基于有机染料催化的β-三氟甲基烯胺化合物制备方法；产物2-氯苄基(E)-3-(苄基氨基)-2-(三氟甲基)丙烯酸酯产率为93％。
本实施例产物的鉴定数据：
1H NMR(400MHz,DMSO-d 6)δ9.11(dt,J＝13.3,6.2Hz,1H),7.84(d,J＝14.1Hz,1H),7.52-7.42(m,2H),7.42-7.26(m,7H),5.27(s,2H),4.56(d,J＝6.2Hz,2H). 19F NMR(376MHz,DMSO-d 6)δ-56.20. 13C NMR(101MHz,DMSO-d 6)δ165.2,154.2(q,J＝5.7Hz),138.6,134.1,132.1,129.7,129.3,129.1,128.7,127.5(2C),127.4,125.7(q,J＝265.5Hz),84.65(q,J＝31.9Hz),62.0,51.8.HR-MS(ESI), m/z(％):Calcd for C 18H 15ClF 3NNaO 2 +[M+Na] +:392.0636,Found:392.0635.
实施例2：
β-三氟甲基烯胺化合物
Ethyl(E)-3-(sec-butylamino)-2-(trifluoromethyl)acrylate的合成：
Figure PCTCN2022124661-appb-000010
在干燥洁净的10mL的石英管中加入聚四氟乙烯磁子，紧接着依次加入CF 3SO 2Na(312.1mg，2.0mmol)、Na 2CO 3(158.9mg，1.5mmol)、Na 2-Eosin Y(0.05mmol，10mol％)、溶剂二甲基亚砜(5.0mL)，搅拌混合均匀后再加入(E)-3-(仲丁氨基)丙烯酸乙酯(85.6mg，0.5mmol)，最后加入叔丁基过氧化氢(192.4μL，2.0mmol)，制得反应液；
在空气氛、室温下，将装有反应液的石英管置于10W白色LEDs(λ max＝455nm)灯照射下搅拌反应12小时并用TLC板监测反应，当反应中(E)-3-(仲丁氨基)丙烯酸乙酯原料消耗直至消失后停止反应；
反应用去离子水洗涤淬灭，之后转移至分液漏斗并用乙酸乙酯萃取，合并有机相，通过无水Na 2SO 4干燥之后过滤，滤液收集至圆底烧瓶并使用旋转蒸发仪减压除去乙酸乙酯，从而得到以(E)-3-(伯胺基)-2-(三氟甲基)丙烯酸酯为主的反应混合物，即(E)-3-(仲丁基氨基)-2-(三氟甲基)丙烯酸乙酯化合物及反应副产物的混合物；
将得到的含有(E)-3-(仲丁基氨基)-2-(三氟甲基)丙烯酸乙酯化合物的反应混合物用300目硅胶色谱柱进行分离纯化，以V 石油醚:V 乙酸乙酯:V 三乙胺＝16:1:0.5为洗脱剂进行过柱，将含有纯(E)-3-(仲丁基氨基)-2-(三氟甲基)丙烯酸乙酯化合物的溶液收集并转移至圆底烧瓶中，用旋转蒸发仪旋除去洗脱剂，即乙酸乙酯、石油醚和三乙胺的混合物，从而得到(E)-3-(仲丁基氨基)-2-(三氟甲基)丙烯酸乙酯纯品；随后，对其进行干燥并称重最终得到109.9mg浅黄色油状(E)-3-(仲丁基氨基)-2-(三氟甲基)丙烯酸乙酯纯品，即为所述的一种基于有机染料催化的β-三氟甲基烯胺化合物制备方法；产物(E)-3-(仲丁基氨基)-2-(三氟甲基)丙烯酸乙酯产率为92％。
本实施例产物的鉴定数据：
1H NMR(400MHz,DMSO-d 6,Major isomer)δ8.58(dd,J＝14.2,8.5Hz,1H),7.63(d,J＝14.0Hz,1H),4.15(q,J＝7.1Hz,2H),3.51-3.39(m,1H),1.52(p,J＝7.3 Hz,2H),1.24-1.16(m,6H),0.85(t,J＝7.4Hz,3H). 19F NMR(376MHz,DMSO-d 6,Major isomer,E/Z≈60/1)δ-56.30. 13C NMR(101MHz,DMSO-d 6,Major isomer)δ166.6,152.9(q,J＝5.7Hz),126.2(q,J＝265.4Hz),84.70(q,J＝31.8Hz),59.5,56.7,30.0,21.3,14.7,10.5.HR-MS(ESI),m/z(％):Calcd for C 10H 16F 3NNaO 2 +[M+Na] +:316.1519,Found:262.1017.
实施例3：
β-三氟甲基烯胺化合物
Ethyl(E)-3-(dibenzylamino)-2-(trifluoromethyl)acrylate的合成：
Figure PCTCN2022124661-appb-000011
在干燥洁净的10mL的石英管中加入聚四氟乙烯磁子，紧接着依次加入CF 3SO 2Na(312.1mg，2.0mmol)、Na 2CO 3(158.9mg，1.5mmol)、Na 2-Eosin Y(0.05mmol，10mol％)、溶剂二甲基亚砜(5.0mL)，搅拌混合均匀后再加入(E)-3-(二苄基氨基)丙烯酸乙酯(147.6mg，0.5mmol)，最后加入叔丁基过氧化氢(192.4μL，2.0mmol)，制得反应液；
在空气氛、室温下，将装有反应液的石英管置于10W白色LEDs(λ max＝455nm)照射下搅拌反应12小时并用TLC板监测反应，当反应中(E)-3-(二苄基氨基)丙烯酸乙酯原料消耗直至消失后停止反应；
反应混合物用去离子水淬灭，之后转移至分液漏斗并用乙酸乙酯萃取，合并有机相，通过无水Na 2SO 4干燥之后过滤，滤液收集至圆底烧瓶并使用旋转蒸发仪减压除去乙酸乙酯,从而得到以(E)-3-(叔胺基)-2-(三氟甲基)丙烯酸酯类衍生物为主的反应混合物，即(E)-3-(二苄基氨基)-2-(三氟甲基)丙烯酸乙酯化合物及反应副产物的混合物；
将得到的含有(E)-3-(二苄基氨基)-2-(三氟甲基)丙烯酸乙酯化合物的反应混合物用300目硅胶色谱柱进行分离纯化，以V 石油醚:V 乙酸乙酯:V 三乙胺＝16:1:0.5为洗脱剂进行过柱，将含有纯(E)-3-(二苄基氨基)-2-(三氟甲基)丙烯酸乙酯化合物的溶液进行收集并转移至圆底烧瓶中，用旋转蒸发仪旋除去洗脱剂，即乙酸乙酯、石油醚和三乙胺的混合物，从而得到(E)-3-(二苄基氨基)-2-(三氟甲基)丙烯酸乙酯纯品；随后，对其进行干燥并称重最终得到148.9mg浅黄色油状(E)-3-(二苄基氨基)-2-(三氟甲基)丙烯酸乙酯纯品，即为所述的一种基于有机染料催化的β-三氟 甲基烯胺化合物制备方法；产物(E)-3-(二苄基氨基)-2-(三氟甲基)丙烯酸乙酯产率为82％。
本实施例产物的鉴定数据：
1H NMR(400MHz,DMSO-d 6,Major isomer)δ7.59(d,J＝4Hz,1H),7.38-7.28(m,6H),7.23-7.19(m,4H)4.60(s,4H),3.97(q,J＝7.1Hz,2H),1.04(t,J＝7.1Hz,3H). 19F NMR(376MHz,DMSO-d 6,Major isomer,E/Z≈10/1)δ-55.38. 13C NMR(100MHz,DMSO-d 6,Major isomer)δ163.4,150.5(q,J＝6.5Hz),129.4,129.2(q,J＝268.7Hz),129.1,128.1,128.0,89.4(q,J＝29.8Hz),60.1,14.5.HR-MS(ESI),m/z(％):Calcd for C 20H 21F 3NO 2 +[M+H] +:364.1519,Found:364.1516.
实施例4：
β-三氟甲基烯胺化合物
Ethyl(E)-3-(dipropylamino)-2-(trifluoromethyl)acrylate的合成
Figure PCTCN2022124661-appb-000012
在干燥洁净的10mL的石英管中加入聚四氟乙烯磁子，紧接着依次加入CF 3SO 2Na(312.1mg，2.0mmol)、Na 2CO 3(158.9mg，1.5mmol)、Na 2-Eosin Y(0.05mmol，10mol％)、溶剂二甲基亚砜(5.0mL)，搅拌混合物使其混合均匀后再往混合中加入(E)-3-(二丙氨基)丙烯酸乙酯(99.6mg，0.5mmol)，最后加入叔丁基过氧化氢(192.4μL，2.0mmol)，制得反应液；
在空气氛、室温下，将装有反应液的石英管置于10W白色LEDs(λ max＝455nm)照射下搅拌反应12小时并用TLC板监测反应，当反应中(E)-3-(二丙氨基)丙烯酸乙酯原料消耗消直至失后停止反应；
反应用去离子水淬灭，之后转移至分液漏斗并用乙酸乙酯萃取，合并有机相，通过无水Na 2SO 4干燥之后过滤，滤液收集至圆底烧瓶中并使用旋转蒸发仪减压除去乙酸乙酯,从而得到以(E)-3-(叔胺基)-2-(三氟甲基)丙烯酸酯类衍生物为主的反应混合物，即(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸乙酯化合物及反应副产物的混合物；
将得到的含有(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸乙酯化合物的反应混合物用300目硅胶色谱柱进行分离纯化，再用V 石油醚:V 乙酸乙酯:V 三乙胺＝16:1:0.5为洗脱剂进行过柱，将含有纯(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸乙酯化合物的溶液收集并转移至圆底烧瓶中，用旋转蒸发仪旋除去洗脱剂，即乙酸乙酯、石油醚和 三乙胺的混合物，从而得到(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸乙酯纯品；随后，对其进行干燥并称重最终得到116.2mg浅黄色油状(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸乙酯纯品，即为所述的一种基于有机染料催化的β-三氟甲基烯胺化合物制备方法；产物(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸乙酯产率为87％。
本实施例产物的鉴定数据：
1H NMR(400MHz,DMSO-d 6,Major isomer)δ7.17(d,J＝1.1Hz,1H),4.09(q,J＝7.1Hz,2H),3.35-3.31(t,J＝7.3Hz,4H,containing one water peak),1.50-1.46(m,4H),1.17(t,J＝7.1Hz,3H),0.79(t,J＝7.4Hz,6H). 19F NMR(376MHz,DMSO-d 6,Major isomer,E/Z≈6.5/1)δ-54.84. 13C NMR(101MHz,DMSO-d 6,Major isomer)δ163.0,149.3(q,J＝6.2Hz),126.44(q,J＝268.9Hz),86.07(q,J＝29.7Hz),59.31,14.23,10.51.HR-MS(ESI),m/z(％):Calcd for C 12H 20F 3NO 2Na +[M+Na] +:290.1338,Found:290.1347.
实施例5：
β-三氟甲基烯胺化合物
(tetrahydrofuran-2-yl)methyl(E)-3-(dipropylamino)-2-(trifluoromethyl)acrylate的合成
Figure PCTCN2022124661-appb-000013
在干燥洁净的10mL的石英管中加入聚四氟乙烯磁子，紧接着依次加入CF 3SO 2Na(312.1mg，2.0mmol)、Na 2CO 3(158.9mg，1.5mmol)、Na 2-Eosin Y(0.05mmol，10mol％)、溶剂二甲基亚砜(5.0mL)，搅拌混合物使其混合均匀后再往混合中加入(四氢呋喃-2-基)甲基(E)-3-(二丙氨基)丙烯酸酯(127.6mg，0.5mmol)，最后加入叔丁基过氧化氢(192.4μL，2.0mmol)，制得反应液；
在空气氛、室温下，将装有反应液的石英管置于10W白色LEDs(λmax＝455nm)照射下搅拌反应12小时并用TLC板监测反应，当反应中(四氢呋喃-2-基)甲基(E)-3-(二丙氨基)丙烯酸酯原料消耗直至消失后停止反应；
反应用去离子水淬灭，之后转移至分液漏斗并用乙酸乙酯萃取，合并有机相，通过无水Na 2SO 4干燥之后过滤，滤液收集圆底烧瓶并使用旋转蒸发仪减压除去乙酸乙酯，从而得到以(E)-3-(叔胺基)-2-(三氟甲基)丙烯酸酯类衍生物为主的反应混合物，即(四氢呋喃-2-基)甲基(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸酯化合 物及反应副产物的混合物；
将得到的含有(四氢呋喃-2-基)甲基(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸酯化合物的反应混合物用300目硅胶色谱柱进行分离纯化，再用V 石油醚:V 乙酸乙酯:V 三乙胺＝16:1:0.5为洗脱剂进行过柱，将含有纯(四氢呋喃-2-基)甲基(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸酯化合物的溶液收集并转移至圆底烧瓶中，用旋转蒸发仪旋除去洗脱剂，即乙酸乙酯、石油醚和三乙胺的混合物，从而得到(四氢呋喃-2-基)甲基(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸酯纯品；随后，对其进行干燥并称重最终得到122.8mg浅黄色油状(四氢呋喃-2-基)甲基(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸酯纯品，即为所述的一种基于有机染料催化的β-三氟甲基烯胺化合物制备方法；产物(四氢呋喃-2-基)甲基(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸酯产率为76％。
本实施例产物的鉴定数据：
1H NMR(400MHz,DMSO-d 6,Major isomer)δ7.20(s,1H),4.02-3.99(m,3H),3.75-3.60(m,2H),3.34(t,J＝7.6Hz,4H),1.95-1.74(m,3H),1.63-1.48(m,5H),0.85-0.78(m,6H). 19F NMR(376MHz,DMSO-d 6,Major isomer,E/Z≈5/1)δ-54.73. 13C NMR(101MHz,DMSO-d 6,Major isomer)δ162.8,149.8(q,J＝6.4Hz),126.4(q,J＝268.0Hz),85.7(q,J＝29.6Hz),75.9,67.5,65.4,27.5,25.2,10.5.HR-MS(ESI),m/z(％):Calcd for C 15H 25F 3NO 3 +[M+H] +:324.1781,Found:324.1792.
实施例6：
β-三氟甲基烯胺化合物
2-chlorobenzyl(E)-3-(dipropylamino)-2-(trifluoromethyl)acrylate的合成
Figure PCTCN2022124661-appb-000014
在干燥洁净的10mL的石英管中加入聚四氟乙烯磁子，紧接着依次加入CF 3SO 2Na(312.1mg，2.0mmol)、Na 2CO 3(158.9mg，1.5mmol)、Na 2-Eosin Y(0.05mmol，10mol％)、溶剂二甲基亚砜(5.0mL)，搅拌混合均匀后再加入2-氯苄基(E)-3-(二丙氨基)丙烯酸酯(147.6mg，0.5mmol)，最后加入叔丁基过氧化氢(192.4μL，2.0mmol)，制得反应液；
在空气氛、室温下，将装有反应液的石英管置于10W白色LEDs(λ max＝455nm)照射下搅拌反应12小时并用TLC板监测反应，当反应中2-氯苄基(E)-3-(二丙氨 基)丙烯酸酯原料消耗直至消失后停止反应；
反应用去离子水淬灭，之后转移至分液漏斗中并用乙酸乙酯萃取，合并有机相，通过无水Na 2SO 4干燥之后过滤，滤液收集至圆底烧瓶并使用旋转蒸发仪减压除去乙酸乙酯,从而得到以(E)-3-(叔胺基)-2-(三氟甲基)丙烯酸酯类衍生物为主的反应混合物，即2-氯苄基(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸酯化合物及反应副产物的混合物；
将得到的含有2-氯苄基(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸酯化合物的反应混合物用300目硅胶色谱柱进行分离纯化，再用V 石油醚:V 乙酸乙酯:V 三乙胺＝16:1:0.5为洗脱剂进行过柱，将含有纯2-氯苄基(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸酯化合物的溶液收集并转移至圆底烧瓶中，用旋转蒸发仪旋除去洗脱剂，即乙酸乙酯、石油醚和三乙胺的混合物，从而得到2-氯苄基(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸酯纯品；随后，对其进行干燥并称重最终得到126.0mg浅黄色油状纯2-氯苄基(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸酯纯品，即为所述的一种基于有机染料催化的β-三氟甲基烯胺化合物制备方法；产物2-氯苄基(E)-3-(二丙氨基)-2-(三氟甲基)丙烯酸酯产率为75％。
本实施例产物的鉴定数据：
1H NMR(400MHz,DMSO-d 6,Major isomer)δ7.47-7.41(m,2H),7.35-7.30(m,2H),7.23(s,1H),5.17(s,2H),3.31(d,J＝7.3Hz,4H),1.60-1.29(m,4H),0.84-0.64(m,6H). 19F NMR(376MHz,DMSO-d 6,Major isomer,E/Z≈5/1)δ-54.47. 13C NMR(101MHz,DMSO-d 6,Major isomer)δ162.3,150.46(q,J＝6.2Hz),134.0,132.3,129.7,129.6,129.3,127.3,126.5(q,J＝267.8Hz),85.14(q,J＝29.9Hz),62.3,10.5.HR-MS(ESI),m/z(％):Calcd for C 17H 22ClF 3NO 2 +[M+H] +:364.1286,Found:364.1286.
实施例7：
β-三氟甲基烯胺化合物
Phenyl(E)-3-(dipropylamino)-2-(trifluoromethyl)acrylate的合成
Figure PCTCN2022124661-appb-000015
在干燥洁净的10mL的石英管中加入聚四氟乙烯磁子，紧接着依次加入 CF 3SO 2Na(312.1mg，2.0mmol)、Na 2CO 3(158.9mg，1.5mmol)、Na 2-Eosin Y(0.05mmol，10mol％)、溶剂二甲基亚砜(5.0mL)，搅拌混合均匀后再加入(E)-3-(二丙氨基)丙烯酸苯酯(123.6mg，0.5mmol)，最后加入叔丁基过氧化氢(192.4μL，2.0mmol)，制得反应液；
在空气氛、室温下，将装有反应液的石英管置于10W白色LEDs(λ max＝455nm)照射下搅拌反应12小时并用TLC板监测反应，当反应中(E)-3-(二丙氨基)丙烯酸苯酯原料消耗直至消失后停止反应；
反应用去离子水淬灭，之后转移至分液漏斗并用乙酸乙酯萃取，合并有机相，通过无水Na 2SO 4干燥之后过滤，滤液收集至圆底烧瓶并使用旋转蒸发仪减压除去乙酸乙酯，从而得到以(E)-3-(叔胺基)-2-(三氟甲基)丙烯酸酯衍生物为主的反应混合物，即(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸苯酯化合物及反应副产物的混合物；
将得到的含有(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸苯酯的反应混合物用300目硅胶色谱柱进行分离纯化，再用V 石油醚:V 乙酸乙酯:V 三乙胺＝16:1:0.5为洗脱剂进行过柱，将含有纯(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸苯酯化合物的溶液收集并转移至圆底烧瓶中，用旋转蒸发仪旋除去洗脱剂，即乙酸乙酯、石油醚和三乙胺的混合物，从而得到(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸苯酯纯品；随后，对其进行干燥并称重最终得到148.0mg浅黄色油状(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸苯酯纯品，即为所述的一种基于有机染料催化的β-三氟甲基烯胺化合物制备方法；产物(E)-3-(二丙基氨基)-2-(三氟甲基)丙烯酸苯酯产率为94％。
本实施例产物的鉴定数据：
1H NMR(400MHz,DMSO-d 6,Major isomer)δ7.47-7.35(m,3H),7.24(t,J＝7.4Hz,1H),7.05(d,J＝7.9Hz,2H),3.40(m,4H),1.69-1.44(m,4H),0.91-0.76(m,6H). 19F NMR(376MHz,DMSO-d 6,Major isomer,E/Z≈6/1)δ-54.42. 13C NMR(101MHz,DMSO-d 6,Major isomer)δ161.1,151.4(d,J＝6.4Hz),150.6,129.5,126.4(d,J＝268.4Hz),125.5,121.8,84.7(d,J＝30.0Hz),10.52.HR-MS(ESI),m/z(％):Calcd for C 16H 21F 3NO 2 +[M+H] +:316.1519,Found:316.1522.
本发明中所实施案例的烯胺底物不仅限于胺源是脂肪族链氨、苄基胺、炔丙胺，其次，氨源是四氢吡咯、吗啉、四氢吡啶及其不同位置上有取代基团时，这些化合物用作反应底物原料，反应依然可以顺利的进行并且能以较高产率给出目标产物。此外，在炔酯底物中，取代基团酯基部分不仅限于烷基酯、苄基酯，当羰基、酰胺为取代基团时，这些化合物依然能够适用于该反应的底物并以令人满意的收率给出目标产物。
最后，应当理解的是，本发明中所述实施例仅用以说明本发明实施例的原则；其他的变形也可能属于本发明的范围；因此，作为示例而非限制，本发明实施例的替代配置可视为与本发明的教导一致；相应地，本发明的实施例不限于本发明明确介绍和描述的实施例。

Claims (6)

  1. 一种β-三氟甲基烯胺化合物，其特征在于，
    所述的β-三氟甲基烯胺化合物的化学结构如式I所示：
    Figure PCTCN2022124661-appb-100001
    其中，所述R 1或R 2为氢、长链烷基、环烷基、苄基、丙炔基及其衍生基团中的任意一种；
    所述EWG为酯基、羰基、酰胺及其衍生基团中的任意一种。
  2. 一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法，其特征在于，其具体步骤包括如下：
    步骤1、往石英反应管中放入聚四氟乙烯磁力搅拌子，随后依次向该石英反应管中加入CF 3SO 2Na、Na 2CO 3、Na 2-Eosin Y和溶剂二甲基亚砜；在室温下搅拌混合均匀后，再加入烯胺及叔丁基过氧化氢，制得反应液；
    步骤2、在空气氛、室温下，将制得的反应液在10W白色LEDs灯下照射并搅拌12小时，通过TLC板监测反应，待反应液中的烯胺被消耗至消失后，停止反应；
    步骤3、将步骤(2)中的反应液用去离子水淬灭，后转移至分液漏斗并用乙酸乙酯萃取，合并有机相通过无水Na 2SO 4干燥之后过滤，滤液收集至圆底烧瓶中，使用旋转蒸发仪减压除去乙酸乙酯，从而制得以三氟甲基烯胺类衍生物为主的反应混合物，即β-三氟甲基烯胺化合物及反应副产物的混合物；
    步骤4、将制得的β-三氟甲基烯胺化合物及反应副产物的混合物用300目硅胶色谱柱进行分离纯化，用V 石油醚：V 乙酸乙酯：V 三乙胺＝16:1:0.5为洗脱剂，收集含有纯β-三氟甲基烯胺类衍生物的溶液并转移至圆底烧瓶中，用旋转蒸发仪除去洗脱剂，即石油醚、乙酸乙酯和三乙胺的混合物，随后，对纯化得到的β-三氟甲基烯胺类衍生物进行干燥并称重，最终得到浅黄色或黄色的油状或固体β-三氟甲基烯胺化合物，即为基于有机染料催化的β-三氟甲基烯胺化合物。
  3. 根据权利要求2所述的一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法，其特征在于，
    在步骤(1)中，所述聚四氟乙烯磁力搅拌子的形状为纺锤型，其计量单位大小为6*10mm。
  4. 根据权利要求2所述的一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法，其特征在于，
    在步骤(1)中，所述烯胺是仲胺基丙烯酸酯或叔胺基丙烯酸酯中的一种；
    其中，所述仲胺基丙烯酸酯的化合物结构为下列结构中的任意一种：
    Figure PCTCN2022124661-appb-100002
    所述叔胺基丙烯酸酯的化合物结构为下列结构中的任意一种：
    Figure PCTCN2022124661-appb-100003
  5. 根据权利要求2所述的一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法，其特征在于，
    在步骤(1)中，所述Na 2-Eosin Y的用量为10mol％；
    所述烯胺、CF 3SO 2Na、Na 2CO 3、叔丁基过氧化氢的反应摩尔比为1:4:3:4；
    所述烯胺在溶剂二甲基亚砜中的浓度为0.1mol/L；
    所述CF 3SO 2Na在溶剂二甲基亚砜中的浓度为0.4mol/L；
    所述Na 2CO 3在溶剂二甲基亚砜中的浓度为0.3mol/L；
    所述叔丁基过氧化氢在溶剂二甲基亚砜中的浓度为0.4mol/L。
  6. 根据权利要求2所述的一种基于有机染料催化的β-三氟甲基烯胺化合物的制备方法，其特征在于，所述室温是：18-33℃。
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