WO2020147861A1 - Electrochemical preparation method for β-trifluoromethylamide compound - Google Patents

Electrochemical preparation method for β-trifluoromethylamide compound Download PDF

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WO2020147861A1
WO2020147861A1 PCT/CN2020/073672 CN2020073672W WO2020147861A1 WO 2020147861 A1 WO2020147861 A1 WO 2020147861A1 CN 2020073672 W CN2020073672 W CN 2020073672W WO 2020147861 A1 WO2020147861 A1 WO 2020147861A1
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electrochemical
trifluoromethyl
compound
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黄玉冰
卢景俊
江虹
李亦彪
朱忠智
陈修文
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五邑大学
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    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
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    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
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    • C25B3/23—Oxidation

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  • the invention relates to the field of organic synthesis, in particular to a method for synthesizing ⁇ -trifluoromethylamide compounds by using arylacetylene compounds under electrochemical oxidation conditions.
  • the reaction system including the transition metal catalyst system and the photo-redox system, which initiates the formation of trifluoromethyl radicals by stoichiometric oxidants or organometallic reagents, has been applied to the trifluoromethyl functionalization of olefins, such as hydrogen/trifluoro Methylation, oxygen/trifluoromethylation, halogen/trifluoromethylation and amino/trifluoromethylation.
  • the technical problem to be solved by the present invention is to provide an electrochemical preparation method of ⁇ -trifluoromethylamide compounds with simpler operation and lower cost.
  • the technical solution adopted by the present invention is: an electrochemical preparation method of ⁇ -trifluoromethyl amide compounds, including the following steps: using aryl acetylene compounds and a trifluoromethyl source as raw materials,
  • the ⁇ -trifluoromethyl amide compound is prepared by an electrochemical anodic oxidation method.
  • the structural formula of the aryl acetylene compound is shown in the following formula (1):
  • R 1 is selected from hydrogen, methyl, fluorine, chlorine, bromine or haloalkyl; more preferably, the aryl group is a phenyl group; more preferably, the alkyl group is an alkyl group with less than eight carbon atoms .
  • the electrochemical anodization method uses at least one of tetra-n-butylammonium tetrafluoroborate, tetra-n-butylammonium acetate, tetra-n-butylammonium hydrogen sulfate and tetra-n-butylammonium hexafluorophosphate as the electrolyte .
  • the molar ratio of the aryl acetylene compound to the electrolyte is 1:0.4 to 1; more preferably, the molar ratio of the aryl acetylene compound to the electrolyte is 1:0.4 to 0.6.
  • the molar ratio of the aryl acetylene compound to the trifluoromethyl source is 1:2 to 4; more preferably, the molar ratio of the aryl acetylene compound to the trifluoromethyl source is 1:2 ⁇ 3.
  • the trifluoromethyl source is selected from at least one of trifluoromethyltrifluorosilane, sodium trifluoromethanesulfinate and Togni reagent; preferably, the fluoromethyl source is selected from trifluoromethyl At least one of methyltrifluorosilane and sodium trifluoromethanesulfinate.
  • the electrochemical anodic oxidation method uses a platinum sheet as a cathode and a carbon rod or another platinum sheet as an anode.
  • the solvent of the reaction system contains acetonitrile; preferably, the solvent may also contain N-pyrrolidone, N,N-dimethylformamide, N,N-dimethylethyl At least one of amide, dichloroethane, methylene chloride, chlorobenzene, ethanol, dimethyl sulfoxide, toluene, xylene, and 1,4-dioxane; more preferably, the solvent is acetonitrile And dichloromethane, and the volume ratio of acetonitrile and dichloromethane is 2-1:1.5.
  • the volume dosage of the solvent is 1.5-10 ml/mmol based on the amount of the aryl acetylene compound; the dosage of the solvent is more preferably 2-5 ml/mmol.
  • the direct current used by the reaction system is 5-20 mA; preferably, the direct current is 10-15 mA.
  • the temperature of the reaction system is 25-40°C; more preferably, the temperature of the reaction system is normal temperature.
  • the electrochemical anodic oxidation reaction time is 6-24 hours; more preferably, 6-12 hours.
  • the preparation method further includes the step of purifying the product obtained by the electrochemical anodic oxidation method: the purification process includes adding ethyl acetate to quench the reaction after the completion of the reaction, then adding saturated brine, washing, and separating The organic phase and the aqueous phase were extracted with ethyl acetate for 3 to 5 times. The organic phases were combined, added with anhydrous sodium sulfate and dried, the solvent was removed by distillation under reduced pressure, and the ⁇ -trifluorophore with higher purity was obtained by column chromatography. Methyl amide compounds.
  • the volumetric amount of ethyl acetate is 5-55 mL/mmol based on the amount of aryl acetylene compounds.
  • the volume dosage of the saturated salt water is 4-30 mL/mmol based on the amount of the aryl acetylene compound.
  • the volumetric amount of ethyl acetate is 4-30 mL/mmol based on the amount of arylacetylene compounds.
  • the beneficial effect of the present invention is that the Langlois reagent (CF 3 SO 2 Na) and other cheap and easily available trifluoromethylation reagents can generate trifluoromethyl radicals through a single-electron oxidation process and release SO 2 at the same time.
  • electrochemical synthesis is a well-known green and sustainable synthesis tool, which provides an effective alternative to conventional chemical methods for redox conversion.
  • electrochemical synthesis avoids the extensive use of chemical oxidants and reducing agents in structurally complex molecules, simplifies the operation steps, and at the same time avoids the use of expensive catalysts and saves production and manufacturing costs; the solution of the invention provides A more convenient and effective olefin trifluoromethyl functionalization scheme was developed, and the application of electrosynthesis was further expanded.
  • the method for the synthesis of ⁇ -trifluoromethylamide derivatives by chemical olefin ammoniating and trifluoromethylation provided by the scheme of the present invention has the advantages of not requiring the use of precious metal catalysts or external oxidants, simple conditions, and waste discharge. Few, good functional group tolerance, mild reaction conditions, high yield and other advantages, suitable for industrial production.
  • the first embodiment of the present invention is: an electrochemical preparation method of ⁇ -trifluoromethyl amide compounds, including the following steps: using the aryl acetylene compound represented by formula (I) as a raw material, trifluoromethyl trifluoromethyl Fluorosilane is used as the source of trifluoromethyl group, by electrochemical anodization, using tetra-n-butylammonium acetate as the electrolyte, reacting for a period of time in a solvent composed of acetonitrile and ethanol, and then purifying and preparing formula (II) The ⁇ -trifluoromethylamide product shown;
  • CF 3 SO 2 Na is used as the trifluoromethyl source
  • acetonitrile is used as the reactant and at the same time as the solvent
  • the cyano group is used as the amide source to realize trifluoromethylation of the ortho amino group
  • Fluoromethyltrifluorosilane is used as a source of trifluoromethyl and tetra-n-butylammonium acetate is used as an electrolyte.
  • the raw materials are low in price, non-toxic and tasteless, and the post-processing is simple and suitable for industrial production.
  • the second embodiment of the present invention is the electrochemical synthesis method of N-(3,3,3-trifluoro-1-phenylpropyl)acetamide:
  • the third embodiment of the present invention is the synthesis of N-(1-(4-(tert-butyl)phenyl)-3,3,3-trifluoropropyl)acetamide:
  • the fourth embodiment of the present invention is: the synthesis of N-(3,3,3-trifluoro-1-(4-fluorophenyl)propyl)acetamide:
  • the fifth embodiment of the present invention is: the synthesis of N-(3,3,3-trifluoro-1-(4-chlorophenyl)propyl)acetamide:
  • the sixth embodiment of the present invention is the synthesis of N-(1-(3-bromophenyl)-3,3,3-trifluoropropyl)acetamide:
  • the seventh embodiment of the present invention is the synthesis of N-(1-(4-(chloromethyl)phenyl)-3,3,3-trifluoropropyl)acetamide:
  • another platinum piece in the present invention is only different from the pole piece in the cathode, that is, if platinum pieces are used as the cathode and anode at the same time, two platinum pieces are used, and the size and material of the two platinum pieces can be completely Consistency is not limited, and it is not the same piece. It is only used for distinguishing and should not be interpreted as any limitation.

Abstract

Disclosed is an electrochemical preparation method for a β-trifluoromethylamide compound, comprising the following steps: using an arylacetylene compound and a trifluoromethyl source as raw materials, and preparing the β-trifluoromethylamide compound by means of electrochemical anodic oxidation. Said preparation method further comprises a step of purifying the product prepared by electrochemical anodic oxidation, the purification treatment process comprising: adding ethyl acetate to quench the reaction after the reaction is completed, adding saturated brine to perform washing, separating the organic phases from the aqueous phase, performing extraction on the aqueous phase using ethyl acetate 3 to 5 times, combining the organic phases, adding anhydrous sodium sulfate for drying, removing the solvent by distillation under reduced pressure, and performing column chromatography to obtain the β-trifluoromethylamide compound having higher purity. Compared with the prior art, the solution of the present invention has the advantages of such as a simple operation, low production costs, and a high yield.

Description

一种β-三氟甲基酰胺类化合物的电化学制备方法Electrochemical preparation method of β-trifluoromethyl amide compound 技术领域Technical field
本发明涉及有机物合成领域，具体涉及一种利用芳基乙炔类化合物在电化学氧化条件下合成β-三氟甲基酰胺类化合物的方法。The invention relates to the field of organic synthesis, in particular to a method for synthesizing β-trifluoromethylamide compounds by using arylacetylene compounds under electrochemical oxidation conditions.
背景技术Background technique
烯烃的邻位双官能化已被认为是通过在相邻碳原子上引入不同基团来快速和直接构建不同分子结构的有效策略。近年来，烯烃的邻位三氟甲基官能化备受关注，由于引入CF 3基团可以显着改变有机分子的物理、化学和生物学性质，因此，含三氟甲基的化合物在医药、农药等领域均有广泛应用。目前，包括过渡金属催化剂体系和光氧化还原体系的反应体系，通过化学计量氧化剂或有机金属试剂引发三氟甲基自由基的形成，已经应用于烯烃的三氟甲基官能化，例如氢/三氟甲基化，氧/三氟甲基化，卤/三氟甲基化和氨基/三氟甲基化。近年来，通过使用亲电子三氟甲基化试剂如Togni试剂(三氟甲基取代高价碘试剂)和Umemoto试剂(S-三氟甲基芳基锍合三氟甲磺酸盐或S-三氟甲基芳基锍合四氟硼酸盐)等进行光催化三氟甲基化反应被多次报道。然而，由于光催化催化剂价格昂贵，使得高成本和三步甲基化试剂的制备步骤繁琐成为阻碍相关应用发展的主要因素。 The ortho-difunctionalization of olefins has been considered as an effective strategy to quickly and directly construct different molecular structures by introducing different groups on adjacent carbon atoms. In recent years, the ortho trifluoromethyl functionalization of olefins has attracted much attention. Since the introduction of CF 3 groups can significantly change the physical, chemical and biological properties of organic molecules, compounds containing trifluoromethyl are used in medicine, Pesticides and other fields are widely used. At present, the reaction system including the transition metal catalyst system and the photo-redox system, which initiates the formation of trifluoromethyl radicals by stoichiometric oxidants or organometallic reagents, has been applied to the trifluoromethyl functionalization of olefins, such as hydrogen/trifluoro Methylation, oxygen/trifluoromethylation, halogen/trifluoromethylation and amino/trifluoromethylation. In recent years, by using electrophilic trifluoromethylation reagents such as Togni reagent (trifluoromethyl substituted hypervalent iodine reagent) and Umemoto reagent (S-trifluoromethylarylsulfonium trifluoromethanesulfonate or S-trifluoromethanesulfonate) The photocatalytic trifluoromethylation reaction of fluoromethyl arylsulfonium tetrafluoroborate) has been reported many times. However, due to the high price of photocatalytic catalysts, the high cost and cumbersome preparation steps of the three-step methylation reagent have become the main factors hindering the development of related applications.
基于此，找出一种操作更简便且成本更低廉的三氟甲基酰胺类化合物具有重要意义。Based on this, it is of great significance to find a trifluoromethyl amide compound with simpler operation and lower cost.
发明内容Summary of the invention
本发明所要解决的技术问题是：提供一种操作更简便且成本更低廉的β-三氟甲基酰胺类化合物的电化学制备方法。The technical problem to be solved by the present invention is to provide an electrochemical preparation method of β-trifluoromethylamide compounds with simpler operation and lower cost.
为了解决上述技术问题，本发明采用的技术方案为：一种β-三氟甲基酰胺类化合物的电化学制备方法，包括以下步骤：以芳基乙炔类化合物和三氟甲基源为原料，通过电化学阳极氧化法制得所述β-三氟甲基酰胺类化合物。In order to solve the above technical problems, the technical solution adopted by the present invention is: an electrochemical preparation method of β-trifluoromethyl amide compounds, including the following steps: using aryl acetylene compounds and a trifluoromethyl source as raw materials, The β-trifluoromethyl amide compound is prepared by an electrochemical anodic oxidation method.
优选地，所述芳基乙炔类化合物的结构式如下式(1)所示：Preferably, the structural formula of the aryl acetylene compound is shown in the following formula (1):
Figure PCTCN2020073672-appb-000001
Figure PCTCN2020073672-appb-000001
式中，R 1选自氢、甲基、氟、氯、溴或卤代烷基；更优选地，所述芳基为苯基；更优选地，所述烷基为八个碳原子以下的烷基。 In the formula, R 1 is selected from hydrogen, methyl, fluorine, chlorine, bromine or haloalkyl; more preferably, the aryl group is a phenyl group; more preferably, the alkyl group is an alkyl group with less than eight carbon atoms .
进一步地，所述电化学阳极氧化法以四正丁基四氟硼酸铵、四正丁基醋酸铵、四正丁基硫酸氢铵和四正丁基六氟磷酸铵中的至少一种为电解质。Further, the electrochemical anodization method uses at least one of tetra-n-butylammonium tetrafluoroborate, tetra-n-butylammonium acetate, tetra-n-butylammonium hydrogen sulfate and tetra-n-butylammonium hexafluorophosphate as the electrolyte .
优选地，所述芳基乙炔类化合物与电解质的摩尔比为1:0.4～1；更优选地，所述芳基乙炔类化合物与电解质的摩尔比为1:0.4～0.6。Preferably, the molar ratio of the aryl acetylene compound to the electrolyte is 1:0.4 to 1; more preferably, the molar ratio of the aryl acetylene compound to the electrolyte is 1:0.4 to 0.6.
优选地，所述芳基乙炔类化合物与三氟甲基源的摩尔比为1:2～4；更优选地，所述芳基乙炔类化合物与三氟甲基源的摩尔比为1:2～3。Preferably, the molar ratio of the aryl acetylene compound to the trifluoromethyl source is 1:2 to 4; more preferably, the molar ratio of the aryl acetylene compound to the trifluoromethyl source is 1:2 ~3.
进一步地，所述三氟甲基源选自三氟甲基三氟硅烷、三氟甲基亚磺酸钠和Togni试剂中的至少一种；优选地，所述氟甲基源选自三氟甲基三氟硅烷和三氟甲基亚磺酸钠中的至少一种。Further, the trifluoromethyl source is selected from at least one of trifluoromethyltrifluorosilane, sodium trifluoromethanesulfinate and Togni reagent; preferably, the fluoromethyl source is selected from trifluoromethyl At least one of methyltrifluorosilane and sodium trifluoromethanesulfinate.
进一步地，所述电化学阳极氧化法以铂片为阴极，碳棒或另一铂片为阳极。Further, the electrochemical anodic oxidation method uses a platinum sheet as a cathode and a carbon rod or another platinum sheet as an anode.
优选地，电化学阳极氧化反应过程中，反应体系的溶剂中含有乙腈；优选地，所述溶剂还可以含有N-吡咯烷酮、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二氯乙烷、二氯甲烷、氯苯、乙醇、二甲基亚砜、甲苯、二甲苯和1,4-二氧六环中的至少一种；更优选地，所述溶剂为乙腈和二氯甲烷的混合液，且乙腈和二氯甲烷的体积比为2～1:1.5。Preferably, during the electrochemical anodic oxidation reaction, the solvent of the reaction system contains acetonitrile; preferably, the solvent may also contain N-pyrrolidone, N,N-dimethylformamide, N,N-dimethylethyl At least one of amide, dichloroethane, methylene chloride, chlorobenzene, ethanol, dimethyl sulfoxide, toluene, xylene, and 1,4-dioxane; more preferably, the solvent is acetonitrile And dichloromethane, and the volume ratio of acetonitrile and dichloromethane is 2-1:1.5.
更优选地，所述溶剂的体积用量以芳基乙炔类化合物的物质的量计为1.5～10ml/mmol；所述溶剂的用量更优选为2～5ml/mmol。More preferably, the volume dosage of the solvent is 1.5-10 ml/mmol based on the amount of the aryl acetylene compound; the dosage of the solvent is more preferably 2-5 ml/mmol.
进一步地，电化学阳极氧化反应过程中，反应体系使用的直流电流为5～20mA；优选地，所述直流电流为10～15mA。Further, during the electrochemical anodic oxidation reaction, the direct current used by the reaction system is 5-20 mA; preferably, the direct current is 10-15 mA.
进一步地，电化学阳极氧化反应过程中，反应体系的温度为25～40℃；更优选地，所述反应体系温度为常温。Further, during the electrochemical anodic oxidation reaction, the temperature of the reaction system is 25-40°C; more preferably, the temperature of the reaction system is normal temperature.
优选地，电化学阳极氧化反应的时间为6～24小时；更优选为6～12小时。Preferably, the electrochemical anodic oxidation reaction time is 6-24 hours; more preferably, 6-12 hours.
进一步地，所述制备方法还包括对电化学阳极氧化法制得的产物进行提纯的步骤：所述提纯处理过程为反应结束后加入乙酸乙酯淬灭反应，再加入饱和食盐水，洗涤，分出有机相，水相再用乙酸乙酯萃取3～5次，合并有机相，加入无水硫酸钠干燥，经减压蒸馏除去溶剂，再经柱层析得到纯度更高的所述β-三氟甲基酰胺类化合物。Further, the preparation method further includes the step of purifying the product obtained by the electrochemical anodic oxidation method: the purification process includes adding ethyl acetate to quench the reaction after the completion of the reaction, then adding saturated brine, washing, and separating The organic phase and the aqueous phase were extracted with ethyl acetate for 3 to 5 times. The organic phases were combined, added with anhydrous sodium sulfate and dried, the solvent was removed by distillation under reduced pressure, and the β-trifluorophore with higher purity was obtained by column chromatography. Methyl amide compounds.
优选地，淬灭反应过程中，乙酸乙酯的体积用量以芳基乙炔类化合物的物质的量计为5～55mL/mmol。Preferably, in the quenching reaction process, the volumetric amount of ethyl acetate is 5-55 mL/mmol based on the amount of aryl acetylene compounds.
优选地，所述饱和食盐水的体积用量以芳基乙炔类化合物的物质的量计为4～30mL/mmol。Preferably, the volume dosage of the saturated salt water is 4-30 mL/mmol based on the amount of the aryl acetylene compound.
优选地，每次萃取过程中，乙酸乙酯的体积用量以芳基乙炔类化合的物质的量计为4～30mL/mmol。Preferably, in each extraction process, the volumetric amount of ethyl acetate is 4-30 mL/mmol based on the amount of arylacetylene compounds.
本发明的有益效果在于：利用Langlois试剂(CF 3SO 2Na)等廉价且易于获得的三氟甲基化试剂，可通过单电子氧化过程产生三氟甲基自由基，同时释放SO 2。一直以来，电化学合成法是众所周知的绿色和可持续的合成工具，为氧化还原转化的常规化学方法提供了有效的替代方案。通过阳极氧化和阴极还原，电化学合成避免了在构造复杂分子中大量使用化学氧化剂和还原剂，简化了操作步骤，同时，避免了昂贵的催化剂的使用，节约了生产制造成本；本发明方案提供了一种更方便和有效的烯烃三氟甲基官能化方案，并进一步扩展了电合成的应用。与现有技术相比，本发明方案提供的化学烯烃氨化三氟甲基化合成β-三氟甲基酰胺类衍生物的方法，具有无需使用贵金属催化剂或外部氧化剂及条件简单、废弃物排放少、官能团耐受性好、反应条件温和、收率高等优点，适于工业生产。 The beneficial effect of the present invention is that the Langlois reagent (CF 3 SO 2 Na) and other cheap and easily available trifluoromethylation reagents can generate trifluoromethyl radicals through a single-electron oxidation process and release SO 2 at the same time. For a long time, electrochemical synthesis is a well-known green and sustainable synthesis tool, which provides an effective alternative to conventional chemical methods for redox conversion. Through anodic oxidation and cathode reduction, electrochemical synthesis avoids the extensive use of chemical oxidants and reducing agents in structurally complex molecules, simplifies the operation steps, and at the same time avoids the use of expensive catalysts and saves production and manufacturing costs; the solution of the invention provides A more convenient and effective olefin trifluoromethyl functionalization scheme was developed, and the application of electrosynthesis was further expanded. Compared with the prior art, the method for the synthesis of β-trifluoromethylamide derivatives by chemical olefin ammoniating and trifluoromethylation provided by the scheme of the present invention has the advantages of not requiring the use of precious metal catalysts or external oxidants, simple conditions, and waste discharge. Few, good functional group tolerance, mild reaction conditions, high yield and other advantages, suitable for industrial production.
具体实施方式detailed description
为详细说明本发明的技术内容、所实现目的及效果，以下结合实施方式予以说明。In order to describe in detail the technical content, the achieved purpose and the effect of the present invention, the following description is combined with the embodiments.
本发明的实施例一为：一种β-三氟甲基酰胺类化合物的电化学制备方法，包括以下步骤：以式(I)所示的芳基乙炔类化合物为原料，三氟甲基三氟硅烷用作三氟甲基源，通过电化学阳极氧化方式，以四正丁基醋酸铵为电解质，在乙腈和乙醇组成的溶剂中反应一段时间后，经提纯处理后制备得到式(II)所示的β-三氟甲基酰胺产物；The first embodiment of the present invention is: an electrochemical preparation method of β-trifluoromethyl amide compounds, including the following steps: using the aryl acetylene compound represented by formula (I) as a raw material, trifluoromethyl trifluoromethyl Fluorosilane is used as the source of trifluoromethyl group, by electrochemical anodization, using tetra-n-butylammonium acetate as the electrolyte, reacting for a period of time in a solvent composed of acetonitrile and ethanol, and then purifying and preparing formula (II) The β-trifluoromethylamide product shown;
Figure PCTCN2020073672-appb-000002
Figure PCTCN2020073672-appb-000002
本发明方案中，以CF 3SO 2Na作为三氟甲基源，乙腈既作为反应物，同时又作为溶剂，氰基用作酰胺源，即可实现邻位的氨基三氟甲基化；三氟甲基三氟硅烷作为三氟甲基源和四正丁基醋酸铵作为电解质，原料价格低廉，无毒无味，后处理简便且适用于工业化生产。 In the scheme of the present invention, CF 3 SO 2 Na is used as the trifluoromethyl source, acetonitrile is used as the reactant and at the same time as the solvent, and the cyano group is used as the amide source to realize trifluoromethylation of the ortho amino group; Fluoromethyltrifluorosilane is used as a source of trifluoromethyl and tetra-n-butylammonium acetate is used as an electrolyte. The raw materials are low in price, non-toxic and tasteless, and the post-processing is simple and suitable for industrial production.
本发明实施例二为：N-(3,3,3-三氟-1-苯基丙基)乙酰胺的电化学合成法：The second embodiment of the present invention is the electrochemical synthesis method of N-(3,3,3-trifluoro-1-phenylpropyl)acetamide:
Figure PCTCN2020073672-appb-000003
Figure PCTCN2020073672-appb-000003
取三口圆底烧瓶，以碳棒作为阳极，铂片作为阴极分别加入苯乙烯52mmg(0.50mmol)，三氟甲基亚磺酸钠234mmg(1.50mmol)，四正丁基六氟磷酸铵194mmg(0.50mmol)，乙腈1.5mL， 二氯甲烷1mL，常温下搅拌反应6小时，反应结束加入乙酸乙酯10mL淬灭反应，加入5mL饱和食盐水洗涤，分出有机相，水相再用乙酸乙酯萃取3次，每次乙酸乙酯用量为5mL，合并有机相，加入无水硫酸钠干燥，经减压蒸馏除去溶剂，再经柱层析得到产物纯品，产物的收率为90％。Take a three-necked round-bottom flask with carbon rod as anode and platinum plate as cathode. Add 52mmg (0.50mmol) of styrene, 234mmg (1.50mmol) of sodium trifluoromethanesulfinate, and 194mmg of tetra-n-butylammonium hexafluorophosphate. 0.50mmol), 1.5mL of acetonitrile, 1mL of dichloromethane, and the reaction was stirred at room temperature for 6 hours. At the end of the reaction, 10mL of ethyl acetate was added to quench the reaction, 5mL of saturated brine was added to wash, and the organic phase was separated. Extract 3 times with 5 mL of ethyl acetate each time, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by distillation under reduced pressure, and then column chromatography to obtain the pure product, the yield of the product is 90%.
取上述产物进行核磁共振波谱法(Nuclear Magnetic Resonance Spectroscopy，NMR)和质谱法(Mass Spectrometry，MS)表征，表征数据如下：The above products were used for nuclear magnetic resonance spectroscopy (Nuclear Magnetic Resonance Spectroscopy, NMR) and mass spectrometry (Mass Spectrometry, MS) characterization, the characterization data are as follows:
1H NMR(500MHz,CDCl 3)δ7.39-7.36(m,2H),7.32(dd,J＝9.6,4.5Hz,3H),5.36(td,J＝8.3,5.9Hz,1H),2.80-2.66(m,1H),2.65-2.52(m,1H),1.98(s,3H)； 1 H NMR (500MHz, CDCl 3 ) δ 7.39-7.36 (m, 2H), 7.32 (dd, J = 9.6, 4.5 Hz, 3H), 5.36 (td, J = 8.3, 5.9 Hz, 1H), 2.80- 2.66(m,1H),2.65-2.52(m,1H),1.98(s,3H);
13C NMR(126MHz,CDCl 3)δ169.6,140.2,129.0,128.1,126.4,125.6(q,J＝267Hz),48.2,39.5(q,J＝27.5Hz),23.1； 13 C NMR(126MHz, CDCl 3 )δ169.6, 140.2, 129.0, 128.1, 126.4, 125.6 (q, J=267Hz), 48.2, 39.5 (q, J=27.5Hz), 23.1;
19F NMR(471MHz,CDCl 3)δ-63.55； 19 F NMR(471MHz, CDCl 3 )δ-63.55;
MS(EI,70eV)m/z:231,188,155,126,106。MS (EI, 70eV) m/z: 231,188,155,126,106.
本发明实施例三为：N-(1-(4-(叔丁基)苯基)-3,3,3-三氟丙基)乙酰胺的合成：The third embodiment of the present invention is the synthesis of N-(1-(4-(tert-butyl)phenyl)-3,3,3-trifluoropropyl)acetamide:
Figure PCTCN2020073672-appb-000004
Figure PCTCN2020073672-appb-000004
取三口圆底烧瓶，以碳棒作为阳极，铂片作为阴极分别加入4-叔丁基苯乙烯80mmg(0.50mmol)，三氟甲基亚磺酸钠234mmg(1.50mmol)，四正丁基六氟磷酸铵194mmg(0.50mmol)，乙腈1.5mL，二氯甲烷1mL，常温下搅拌反应6小时，反应结束加入乙酸乙酯10mL淬灭反应，加入5mL饱和食盐水洗涤，分出有机相，水相再用乙酸乙酯萃取3次，每次乙酸乙酯用量为5mL，合并有机相，加入无水硫酸钠干燥，经减压蒸馏除去溶剂，再经柱层析得到产物纯品，产物的收率为86％。Take a three-necked round-bottomed flask with carbon rod as anode and platinum sheet as cathode. Add 80mmg (0.50mmol) of 4-tert-butylstyrene, 234mmg (1.50mmol) of sodium trifluoromethanesulfinate, and tetra-n-butylhexanol. 194mmg (0.50mmol) of ammonium fluorophosphate, 1.5mL of acetonitrile, 1mL of dichloromethane, and the reaction was stirred at room temperature for 6 hours. At the end of the reaction, 10mL of ethyl acetate was added to quench the reaction, and washed with 5mL of saturated brine. The organic phase and the aqueous phase were separated. Then extract with ethyl acetate 3 times, the amount of ethyl acetate each time is 5mL, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by distillation under reduced pressure, and then column chromatography to obtain the pure product, the yield of the product Is 86%.
取上述产物进行NMR和MS表征，表征数据如下：Take the above products for NMR and MS characterization, the characterization data are as follows:
1H NMR(500MHz,CDCl 3)δ7.40(d,J＝8.3Hz,2H),7.25(d,J＝8.3Hz,2H),5.90(s,1H),5.35(d,J＝6.2Hz,1H),2.81-2.70(m,1H),2.65-2.56(m,1H),2.01(s,3H),1.33(s,9H)； 1 H NMR(500MHz,CDCl 3 )δ7.40(d,J=8.3Hz,2H), 7.25(d,J=8.3Hz,2H), 5.90(s,1H), 5.35(d,J=6.2Hz ,1H),2.81-2.70(m,1H),2.65-2.56(m,1H),2.01(s,3H),1.33(s,9H);
13C NMR(126MHz,CDCl 3)δ169.3,151.3,136.8,126.4(q,J＝37.8Hz),126.1,126.0,47.9,39.3(q,J＝27.5Hz),34.6,31.3,23.4； 13 C NMR(126MHz, CDCl 3 )δ169.3, 151.3, 136.8, 126.4 (q, J=37.8Hz), 126.1, 126.0, 47.9, 39.3 (q, J=27.5Hz), 34.6, 31.3, 23.4;
19F NMR(471MHz,CDCl 3)δ-63.38； 19 F NMR(471MHz, CDCl 3 )δ-63.38;
MS(EI,70eV)m/z:287,272,230,188。MS (EI, 70eV) m/z: 287,272,230,188.
本发明实施例四为：N-(3,3,3-三氟-1-(4-氟苯基)丙基)乙酰胺的合成：The fourth embodiment of the present invention is: the synthesis of N-(3,3,3-trifluoro-1-(4-fluorophenyl)propyl)acetamide:
Figure PCTCN2020073672-appb-000005
Figure PCTCN2020073672-appb-000005
取三口圆底烧瓶，以碳棒作为阳极，铂片作为阴极分别加入4-氟苯乙烯61mmg(0.50mmol)，三氟甲基亚磺酸钠156mmg(1.00mmol)，四正丁六氟磷酸铵194mmg(0.50mmol)，乙腈1.5mL，二氯乙烷1.5mL，常温下搅拌反应6小时，反应结束加入乙酸乙酯10mL淬灭反应，加入5mL饱和食盐水洗涤，分出有机相，水相再用乙酸乙酯萃取3次，每次乙酸乙酯用量为5mL，合并有机相，加入无水硫酸钠干燥，经减压蒸馏除去溶剂，再经柱层析得到产物纯品，产物的收率为85％。Take a three-necked round-bottom flask with carbon rod as anode and platinum sheet as cathode. Add 61mmg (0.50mmol) of 4-fluorostyrene, 156mmg (1.00mmol) of sodium trifluoromethanesulfinate, and ammonium tetra-n-butylhexafluorophosphate. 194mmg (0.50mmol), 1.5mL of acetonitrile, 1.5mL of dichloroethane, and the reaction was stirred at room temperature for 6 hours. At the end of the reaction, 10mL of ethyl acetate was added to quench the reaction, washed with 5mL of saturated brine, the organic phase was separated, and the aqueous phase was again Extract 3 times with ethyl acetate, the amount of ethyl acetate each time is 5mL, combine the organic phases, add anhydrous sodium sulfate and dry, remove the solvent by distillation under reduced pressure, and then column chromatography to obtain the pure product. The yield of the product is 85%.
取上述产物进行NMR和MS表征，表征数据如下：Take the above products for NMR and MS characterization, the characterization data are as follows:
1H NMR(500MHz,CDCl 3)δ7.30(dd,J＝6.0,2.7Hz,2H),7.08-7.04(m,2H),5.33(dd,J＝14.1,8.1Hz,1H),2.79-2.67(m,1H),2.56(pd,J＝10.3,5.5Hz,1H),1.99(s,3H)； 1 H NMR (500MHz, CDCl 3 ) δ 7.30 (dd, J = 6.0, 2.7 Hz, 2H), 7.08-7.04 (m, 2H), 5.33 (dd, J = 14.1, 8.1 Hz, 1H), 2.79- 2.67(m,1H),2.56(pd,J=10.3,5.5Hz,1H),1.99(s,3H);
13C NMR(126MHz,CDCl 3)δ169.6,162.4(d,J＝247.3Hz),135.9,128.2(d,J＝8.2Hz),126.5(q,J＝277.6Hz),115.9(d,J＝21.8Hz),47.8(d,J＝2.5Hz),39.5(q,J＝27.7Hz),23.2. 19F NMR(471MHz,CDCl 3)δ-63.53,-113.81；MS(EI,70eV)m/z:249,138,124。 13 C NMR (126MHz, CDCl 3 ) δ169.6, 162.4 (d, J = 247.3Hz), 135.9, 128.2 (d, J = 8.2Hz), 126.5 (q, J = 277.6Hz), 115.9 (d, J = 21.8 hz), 47.8 (d, J = 2.5Hz), 39.5 (q, J = 27.7Hz), 23.2 19 F NMR (471MHz, CDCl 3) δ-63.53, -113.81;. MS (EI, 70eV) m / z : 249,138,124.
本发明实施例五为：N-(3,3,3-三氟-1-(4-氯苯基)丙基)乙酰胺的合成：The fifth embodiment of the present invention is: the synthesis of N-(3,3,3-trifluoro-1-(4-chlorophenyl)propyl)acetamide:
Figure PCTCN2020073672-appb-000006
Figure PCTCN2020073672-appb-000006
取三口圆底烧瓶，以碳棒作为阳极，铂片作为阴极分别加入4-氯苯乙烯69mmg(0.50mmol)，三氟甲基亚磺酸钠156mmg(1.00mmol)，四正丁基六氟磷酸铵97mmg(0.25mmol)，乙腈1.5mL，二氯乙烷1.5mL，常温下搅拌反应6小时，反应结束加入乙酸乙酯10mL淬灭反应，加入5mL饱和食盐水洗涤，分出有机相，水相再用乙酸乙酯萃取3次，每次乙酸乙酯用量为5mL，合并有机相，加入无水硫酸钠干燥，经减压蒸馏除去溶剂，再经 柱层析得到产物纯品，产物的收率为88％。Take a three-necked round-bottom flask with carbon rod as anode and platinum sheet as cathode. Add 69mmg (0.50mmol) of 4-chlorostyrene, 156mmg (1.00mmol) of sodium trifluoromethanesulfinate, and tetra-n-butylhexafluorophosphoric acid. 97mmg (0.25mmol) of ammonium, 1.5mL of acetonitrile, 1.5mL of dichloroethane, and the reaction was stirred at room temperature for 6 hours. At the end of the reaction, 10mL of ethyl acetate was added to quench the reaction, and washed with 5mL of saturated brine. The organic phase and the aqueous phase were separated. Then extract with ethyl acetate 3 times, the amount of ethyl acetate each time is 5mL, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by distillation under reduced pressure, and then column chromatography to obtain the pure product, the yield of the product Is 88%.
取上述产物进行NMR和MS表征，表征数据如下：Take the above products for NMR and MS characterization, the characterization data are as follows:
1H NMR(500MHz,CDCl 3)δ7.33(d,J＝8.5Hz,2H),7.24(d,J＝8.5Hz,2H),6.38(d,J＝7.4Hz,1H),5.30(dd,J＝10.9,5.1Hz,1H),2.73-2.66(m,1H),2.57-2.50(m,1H),1.98(s,3H)； 1 H NMR(500MHz, CDCl 3 )δ7.33(d,J=8.5Hz,2H), 7.24(d,J=8.5Hz,2H), 6.38(d,J=7.4Hz,1H), 5.30(dd , J = 10.9, 5.1 Hz, 1H), 2.73-2.66 (m, 1H), 2.57-2.50 (m, 1H), 1.98 (s, 3H);
13C NMR(126MHz,CDCl 3)δ169.58,138.57,133.98,129.17,127.81,125.4(q,J＝277.5Hz),47.77,39.35(q,J＝27.6Hz),23.20； 13 C NMR(126MHz, CDCl 3 )δ169.58,138.57,133.98,129.17,127.81,125.4(q,J=277.5Hz),47.77,39.35(q,J=27.6Hz),23.20;
19F NMR(471MHz,CDCl 3)δ-63.46(t,J＝10.3Hz)； 19 F NMR (471MHz, CDCl 3 )δ-63.46 (t, J=10.3Hz);
MS(EI,70eV)m/z:265,222,188,154,140。MS (EI, 70eV) m/z: 265, 222, 188, 154, 140.
本发明实施例六为：N-(1-(3-溴苯基)-3,3,3-三氟丙基)乙酰胺的合成：The sixth embodiment of the present invention is the synthesis of N-(1-(3-bromophenyl)-3,3,3-trifluoropropyl)acetamide:
Figure PCTCN2020073672-appb-000007
Figure PCTCN2020073672-appb-000007
取三口圆底烧瓶，以碳棒作为阳极，铂片作为阴极分别加入3-溴苯乙烯91mmg(0.50mmol)，三氟甲基亚磺酸钠156mmg(1.00mmol)，四正丁基六氟磷酸铵97mmg(0.25mmol)，乙腈1.5mL，二氯乙烷1.5mL，常温下搅拌反应6小时，反应结束加入乙酸乙酯10mL淬灭反应，加入5mL饱和食盐水洗涤，分出有机相，水相再用乙酸乙酯萃取3次，每次乙酸乙酯用量为5mL，合并有机相，加入无水硫酸钠干燥，经减压蒸馏除去溶剂，再经柱层析得到产物纯品，产物的收率为89％。Take a three-necked round-bottom flask with carbon rod as anode and platinum plate as cathode. Add 91mmg (0.50mmol) of 3-bromostyrene, 156mmg (1.00mmol) of sodium trifluoromethanesulfinate, and tetra-n-butylhexafluorophosphate. 97mmg (0.25mmol) of ammonium, 1.5mL of acetonitrile, 1.5mL of dichloroethane, and the reaction was stirred at room temperature for 6 hours. At the end of the reaction, 10mL of ethyl acetate was added to quench the reaction, and washed with 5mL of saturated brine. The organic phase and the aqueous phase were separated. Then extract with ethyl acetate 3 times, the amount of ethyl acetate each time is 5mL, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by distillation under reduced pressure, and then column chromatography to obtain the pure product, the yield of the product Is 89%.
取上述产物进行NMR和MS表征，表征数据如下：Take the above products for NMR and MS characterization, the characterization data are as follows:
1H NMR(500MHz,CDCl 3)δ7.48(d,J＝1.6Hz,1H),7.44(dt,J＝7.1,1.8Hz,1H),7.26-7.22(m,2H),5.33(td,J＝8.6,5.3Hz,1H),2.72-2.62(m,1H),2.53(ddt,J＝15.3,10.2,5.1Hz,1H),2.00(s,3H)； 1 H NMR (500MHz, CDCl 3 ) δ7.48 (d, J = 1.6 Hz, 1H), 7.44 (dt, J = 7.1, 1.8 Hz, 1H), 7.26-7.22 (m, 2H), 5.33 (td, J = 8.6, 5.3 Hz, 1H), 2.72-2.62 (m, 1H), 2.53 (ddt, J = 15.3, 10.2, 5.1 Hz, 1H), 2.00 (s, 3H);
13C NMR(126MHz,CDCl 3)δ169.7,142.5,131.2,130.6,129.4,125.4(q,J＝277.6Hz),125.2,123.0,47.8,47.8,47.8,39.4(q,J＝27.8Hz),23.2； 13 C NMR (126MHz, CDCl 3 ) δ 169.7, 142.5, 131.2, 130.6, 129.4, 125.4 (q, J = 277.6 Hz), 125.2, 123.0, 47.8, 47.8, 47.8, 39.4 (q, J = 27.8 Hz), 23.2 ；
19F NMR(471MHz,CDCl 3)δ-63.59； 19 F NMR(471MHz, CDCl 3 )δ-63.59;
MS(EI,70eV)m/z:309,252,228,184。MS (EI, 70eV) m/z: 309,252,228,184.
本发明实施例七为：N-(1-(4-(氯甲基)苯基)-3,3,3-三氟丙基)乙酰胺的合成：The seventh embodiment of the present invention is the synthesis of N-(1-(4-(chloromethyl)phenyl)-3,3,3-trifluoropropyl)acetamide:
Figure PCTCN2020073672-appb-000008
Figure PCTCN2020073672-appb-000008
取三口圆底烧瓶，以碳棒作为阳极，铂片作为阴极分别加入1-(氯甲基)-4-乙烯基苯76mmg(0.50mmol)，三氟甲基亚磺酸钠156mmg(1.00mmol)，四正丁基六氟磷酸铵97mmg(0.25mmol)，乙腈1.5mL，二氯乙烷1.5mL，常温下搅拌反应6小时，反应结束加入乙酸乙酯10mL淬灭反应，加入5mL饱和食盐水洗涤，分出有机相，水相再用乙酸乙酯萃取3次，每次乙酸乙酯用量为5mL，合并有机相，加入无水硫酸钠干燥，经减压蒸馏除去溶剂，再经柱层析得到产物纯品，产物的收率为94％。Take a three-necked round-bottom flask, use carbon rod as anode and platinum sheet as cathode, respectively add 76mmg (0.50mmol) of 1-(chloromethyl)-4-vinylbenzene and 156mmg (1.00mmol) of sodium trifluoromethanesulfinate , Tetra-n-butylammonium hexafluorophosphate 97mmg (0.25mmol), 1.5mL of acetonitrile, 1.5mL of dichloroethane, and the reaction was stirred at room temperature for 6 hours. At the end of the reaction, 10mL of ethyl acetate was added to quench the reaction, and 5mL of saturated brine was added to wash , Separate the organic phase, extract the aqueous phase with ethyl acetate 3 times, the amount of ethyl acetate each time is 5mL, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by distillation under reduced pressure, and then column chromatography to obtain The product is pure, and the yield of the product is 94%.
取上述产物进行NMR和MS表征，表征数据如下：Take the above products for NMR and MS characterization, the characterization data are as follows:
1H NMR(500MHz,CDCl 3)δ7.39(d,J＝8.1Hz,2H),7.31(d,J＝8.1Hz,2H),6.41(d,J＝7.6Hz,1H),5.36(dd,J＝14.0,8.2Hz,1H),4.59(s,2H),2.76–2.66(m,1H),2.57(ddt,J＝15.5,10.4,5.1Hz,1H),1.99(s,3H)； 1 H NMR (500MHz, CDCl 3 ) δ 7.39 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 6.41 (d, J = 7.6 Hz, 1H), 5.36 (dd ,J=14.0,8.2Hz,1H),4.59(s,2H),2.76-2.66(m,1H), 2.57(ddt,J=15.5,10.4,5.1Hz,1H),1.99(s,3H);
13C NMR(126MHz,CDCl 3)δ169.6,140.3,137.4,129.28,126.8,125.3(d,J＝243.2Hz),48.0,39.4(q,J＝27.6Hz),45.7,23.2； 13 C NMR (126MHz, CDCl 3 ) δ169.6, 140.3, 137.4, 129.28, 126.8, 125.3 (d, J = 243.2 Hz), 48.0, 39.4 (q, J = 27.6 Hz), 45.7, 23.2;
19F NMR(471MHz,CDCl 3)δ-63.48； 19 F NMR(471MHz, CDCl 3 )δ-63.48;
MS(EI,70eV)m/z:279,244,202,188,154。MS (EI, 70eV) m/z: 279,244,202,188,154.
本发明中所称“另一铂片”仅为区别于阴极中的极片，即若同时采用铂片作为阴阳极时，是取用两块铂片，两块铂片的大小材质均可完全一致，并不作限定，非同一块即可，仅作区分标识，不应理解为任何限定作用。The term "another platinum piece" in the present invention is only different from the pole piece in the cathode, that is, if platinum pieces are used as the cathode and anode at the same time, two platinum pieces are used, and the size and material of the two platinum pieces can be completely Consistency is not limited, and it is not the same piece. It is only used for distinguishing and should not be interpreted as any limitation.
以上所述仅为本发明的实施例，并非因此限制本发明的专利范围，凡是利用本发明说明书内容所作的等同变换，或直接或间接运用在相关的技术领域，均同理包括在本发明的专利保护范围内。The above are only the embodiments of the present invention and do not limit the scope of the present invention. Any equivalent transformations made using the content of the present invention description, or directly or indirectly applied in related technical fields, are all included in the present invention. Within the scope of patent protection.

Claims (10)

  1. 一种β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：包括以下步骤：以芳基乙炔类化合物和三氟甲基源为原料，通过电化学阳极氧化法制得所述β-三氟甲基酰胺类化合物。An electrochemical preparation method of β-trifluoromethyl amide compounds, characterized in that it comprises the following steps: using aryl acetylene compounds and a trifluoromethyl source as raw materials, the β-trifluoromethyl amide compound is prepared by an electrochemical anodic oxidation method. -Trifluoromethyl amide compounds.
  2. 根据权利要求1所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：所述芳基乙炔类化合物的结构式如下式(1)所示：The electrochemical preparation method of β-trifluoromethyl amide compounds according to claim 1, wherein the structural formula of the aryl acetylene compound is shown in the following formula (1):
    Figure PCTCN2020073672-appb-100001
    Figure PCTCN2020073672-appb-100001
    式中，R 1选自氢、甲基、氟、氯、溴或卤代烷基；更优选地，所述芳基为苯基；更优选地，所述烷基为八个碳原子以下的烷基。 In the formula, R 1 is selected from hydrogen, methyl, fluorine, chlorine, bromine or haloalkyl; more preferably, the aryl group is a phenyl group; more preferably, the alkyl group is an alkyl group with less than eight carbon atoms .
  3. 根据权利要求1所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：所述电化学阳极氧化法以四正丁基四氟硼酸铵、四正丁基醋酸铵、四正丁基硫酸氢铵和四正丁基六氟磷酸铵中的至少一种为电解质；优选地，所述芳基乙炔类化合物与电解质的摩尔比为1:0.4～1；更优选地，所述芳基乙炔类化合物与电解质的摩尔比为1:0.4～0.6。The electrochemical preparation method of β-trifluoromethyl amide compounds according to claim 1, characterized in that: the electrochemical anodization method uses tetra-n-butylammonium tetrafluoroborate, tetra-n-butylammonium acetate, At least one of tetra-n-butylammonium hydrogen sulfate and tetra-n-butylammonium hexafluorophosphate is an electrolyte; preferably, the molar ratio of the arylacetylene compound to the electrolyte is 1:0.4-1; more preferably, The molar ratio of the aryl acetylene compound to the electrolyte is 1:0.4-0.6.
  4. 根据权利要求1所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：所述芳基乙炔类化合物与三氟甲基源的摩尔比为1:2～4；更优选地，所述芳基乙炔类化合物与三氟甲基源的摩尔比为1:2～3。The electrochemical preparation method of β-trifluoromethyl amide compounds according to claim 1, wherein the molar ratio of the aryl acetylene compound to the trifluoromethyl source is 1:2 to 4; Preferably, the molar ratio of the aryl acetylene compound to the trifluoromethyl source is 1:2~3.
  5. 根据权利要求1所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：所述三氟甲基源选自三氟甲基三氟硅烷、三氟甲基亚磺酸钠和Togni试剂中的至少一种；优选地，所述氟甲基源选自三氟甲基三氟硅烷和三氟甲基亚磺酸钠中的至少一种。The electrochemical preparation method of β-trifluoromethyl amide compounds according to claim 1, wherein the trifluoromethyl source is selected from the group consisting of trifluoromethyltrifluorosilane and trifluoromethylsulfinic acid At least one of sodium and Togni reagent; preferably, the fluoromethyl source is selected from at least one of trifluoromethyltrifluorosilane and sodium trifluoromethanesulfinate.
  6. 根据权利要求1所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：电化学阳极氧化反应过程中，反应体系的溶剂中含有乙腈；所述溶剂还含有N-吡咯烷酮、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二氯乙烷、二氯甲烷、氯苯、乙醇、二甲基亚砜、甲苯、二甲苯和1,4-二氧六环中的至少一种；优选地，所述溶剂的体积用量以芳基乙炔类化合物的物质的量计优选为1.5～10ml/mmol；所述溶剂的用量更优选为2～5ml/mmol。The electrochemical preparation method of β-trifluoromethylamide compounds according to claim 1, characterized in that: during the electrochemical anodization reaction, the solvent of the reaction system contains acetonitrile; the solvent also contains N-pyrrolidone , N,N-dimethylformamide, N,N-dimethylacetamide, dichloroethane, dichloromethane, chlorobenzene, ethanol, dimethyl sulfoxide, toluene, xylene and 1,4- At least one of dioxane; preferably, the volume dosage of the solvent is 1.5-10ml/mmol based on the amount of the arylacetylene compound; the dosage of the solvent is more preferably 2-5ml/ mmol.
  7. 根据权利要求6所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：所述溶剂为乙腈和二氯甲烷的混合液，且乙腈和二氯甲烷的体积比为2～1:1.5。The electrochemical preparation method of β-trifluoromethyl amide compounds according to claim 6, wherein the solvent is a mixture of acetonitrile and dichloromethane, and the volume ratio of acetonitrile and dichloromethane is 2 ~ 1:1.5.
  8. 根据权利要求1所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：所述电化学阳极氧化法以铂片为阴极，碳棒或另一铂片为阳极；电化学阳极氧化反应过程中，反应体系使用的直流电流为5～20mA；优选地，所述直流电流为10～15mA；电化学阳极氧化反 应过程中，反应体系的温度为25～40℃；电化学阳极氧化反应的时间为6～24小时；更优选为6～12小时。The electrochemical preparation method of β-trifluoromethylamide compounds according to claim 1, wherein the electrochemical anodic oxidation method uses a platinum sheet as a cathode and a carbon rod or another platinum sheet as an anode; During the chemical anodic oxidation reaction, the direct current used by the reaction system is 5-20 mA; preferably, the direct current is 10-15 mA; during the electrochemical anodic oxidation reaction, the temperature of the reaction system is 25-40°C; The anodic oxidation reaction time is 6 to 24 hours; more preferably 6 to 12 hours.
  9. 根据权利要求1-8任一项所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：所述制备方法还包括对电化学阳极氧化法制得的产物进行提纯的步骤：The electrochemical preparation method of β-trifluoromethyl amide compounds according to any one of claims 1-8, characterized in that: the preparation method further comprises a step of purifying the product obtained by the electrochemical anodization method :
    所述提纯处理过程为反应结束后加入乙酸乙酯淬灭反应，再加入饱和食盐水，洗涤，分出有机相，水相再用乙酸乙酯萃取3～5次，合并有机相，加入无水硫酸钠干燥，经减压蒸馏除去溶剂，再经柱层析得到纯度更高的所述β-三氟甲基酰胺类化合物。The purification process is that after the reaction is completed, ethyl acetate is added to quench the reaction, then saturated brine is added, washed, and the organic phase is separated, the aqueous phase is extracted with ethyl acetate for 3 to 5 times, the organic phases are combined, and anhydrous is added It is dried over sodium sulfate, the solvent is removed by distillation under reduced pressure, and the β-trifluoromethylamide compound with higher purity is obtained by column chromatography.
  10. 根据权利要求9所述的β-三氟甲基酰胺类化合物的电化学制备方法，其特征在于：淬灭反应过程中，乙酸乙酯的体积用量以芳基乙炔类化合物的物质的量计为5～55mL/mmol；所述饱和食盐水的体积用量以芳基乙炔类化合物的物质的量计为4～30mL/mmol；每次萃取过程中，乙酸乙酯的体积用量以芳基乙炔类化合的物质的量计为4～30mL/mmol。The electrochemical preparation method of β-trifluoromethyl amide compounds according to claim 9, characterized in that: in the quenching reaction process, the volume of ethyl acetate is calculated as the amount of aryl acetylene compounds 5～55mL/mmol; The volume and dosage of the saturated brine is 4～30mL/mmol based on the amount of arylacetylene compounds; in each extraction process, the volume and dosage of ethyl acetate is based on arylacetylene compounds The amount of the substance is 4-30mL/mmol.
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