Preparation method of trifluorovinyl alkyl ether compounds and intermediates thereof

Abstract

The present invention discloses a method for preparing a trifluorovinyl ether compound and an intermediate thereof. The present invention provides a method for preparing a trifluorovinyl ether compound, which comprises the following steps: in an organic solvent, in the presence of an initiator, an etherification reaction is carried out between a sodium salt and / or a potassium salt of an alcohol compound containing a fragment as shown in formula I and a 1,2-dihalotetrafluoroethane as shown in formula XCF2CF2X to obtain a 2-halogen-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula II (corresponding to the alcohol compound); wherein X is the halogen, which is independently chlorine or bromine; M is sodium or potassium; C sp3 It indicates that the C connected to O is an sp3 hybridized carbon atom. The preparation method involved in the present invention has cheap and readily available raw materials, mild reaction conditions, simple operation, low cost and easy promotion.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing a trifluorovinyl alkyl ether compound and an intermediate thereof. Background Art

[0002] There are two main categories of trifluorovinyl ethers, one is trifluorovinyl aryl ether and the other is trifluorovinyl alkyl ether.

[0003] Trifluorovinyl aryl ether is an important monomer for polymer synthesis, mainly used for synthesizing polymers containing hexafluorocyclobutane structure. The most widely used method for synthesizing the monomer of trifluorovinyl aryl ether is to use phenol as raw material, directly react with the easily available BrCF2CF2Br under alkaline conditions to obtain 2-bromo-1,1,2,2-tetrafluoroaryl ether (ArOCF2CF2Br), and then obtain trifluorovinyl aryl ether by zinc powder dehalogenation. The synthesis of trifluorovinyl aryl ether is relatively simple because it is relatively easy to synthesize 1,2-dihalotetrafluoroethyl aryl ether compounds directly from phenol, and the reagents used are safe and easy to operate. However, there is a significant disadvantage in the direct zinc powder dehalogenation step: a considerable amount of by-product 1,1,2,2-tetrafluoroaryl ether (ArOCF2CF2H) is generated, and the boiling point and polarity of this by-product are very close to those of the main product, which brings great difficulties to separation and purification (CN106631716A, 2017).

[0004] The research on the corresponding trifluorovinyl alkyl ethers mainly focuses on perfluoro(alkyl vinyl ether) (R f OCF=CF2, PAVE), such as perfluoro(methyl vinyl ether) (CF3OCF=CF2, PMVE), perfluoro(ethyl vinyl ether) (CF3CF2OCF=CF2, PEVE) and perfluoro(propyl vinyl ether) (CF3CF2CF2OCF=CF2, PPVE). This class of compounds is widely used in the synthesis of fluororesins.

[0005] Compared with the above two widely studied and applied trifluorovinyl ethers, another type of trifluorovinyl alkyl ether (oxygen atom is directly connected to non-perfluoroalkyl carbon atom) is rarely studied. This is mainly because the reported synthesis methods for this type of trifluorovinyl alkyl ether are few and not efficient. There are three main synthesis methods: one is Pellerite's report on the use of hexafluoropropylene oxide to obtain trifluorovinyl ether by thermal decomposition of potassium salt of 2-alkoxytetrafluoropropionic acid (J. Fluor. Chem. 1990, 49, 43). Even after continuous improvement, the yield is not ideal. Only the yield of trifluorovinyl ether substituted with trifluoroethoxy (CF3CH2O-) can reach a moderate yield (67%), while the yield of trifluorovinyl ethyl ether (EtOCF=CF2) substituted with potassium salt of tetrafluoropropionic acid substituted with ethoxy (EtO-) can only obtain about 10% of the yield.

[0006] The second is the direct reaction of sodium alcoholate and tetrafluoroethylene to prepare trifluorovinyl alkyl ether reported by Dixon and Kojima et al. (US Patent 2,917,548,1959; Chem.Soc.Jpn.1962,35,532). This is the method commonly used to synthesize trifluorovinyl alkyl ether. However, this method requires the use of tetrafluoroethylene gas at a relatively high pressure and heating, and has strict requirements on experimental operation. If the operation is improper, there will be a risk of explosion. In addition, it is difficult to obtain high-purity sodium alcoholate, and when the sodium alcoholate reacting with tetrafluoroethylene is mixed with raw alcohol, under this reaction condition, the alcohol can react with tetrafluoroethylene to generate a by-product tetrafluoroethyl alkyl ether (ROCF2CF2H). This method is mainly used to prepare some simple trifluorovinyl alkyl ethers, such as CF2=CFOCH3 and CF2=CFOCH2CH3, and the yield is generally low, especially for some complex trifluorovinyl alkyl ethers (for example, the examples given in the US patents show that the calculated yield of nBu ether is 40%, and that of nPr ether is 10%; the yields of Me ether, Et ether and iPr ether in Japanese literature are 28%, 53% and 26% respectively).

[0007] Third, Liu Bo et al. recently disclosed that tetrafluoropropyl trifluorovinyl ether was prepared from trifluoroethylene gas through the reaction of 1,2-dibromo-1,1,2-trifluoroethane intermediate and 2,2,3,3-tetrafluoropropanol (CN111018679A, 2020), but it was limited to one report of tetrafluoropropyl trifluorovinyl ether, and 1,2-dibromo-1,1,2-trifluoroethane was prepared from trifluoroethylene; however, trifluoroethylene gas is a by-product produced in the production process of tetrafluoroethylene and is not easy to obtain.

[0008] The synthesis of trifluorovinyl alkyl ether (ROCF=CF2) is generally prepared by the second method mentioned above, that is, the alcohol substrate is reacted with sodium alcoholate and tetrafluoroethylene gas (there is a risk of explosion, and tetrafluoroethylene gas is not easy to be transported outside the place of production), instead of using phenolic substrates to react with safe and easily available XCF2CF2X (X is chlorine or bromine) and then dehalogenating with zinc powder to obtain trifluorovinyl alkyl ether as in the synthesis of trifluorovinyl aryl ether. The main reason is that there is currently a lack of universal methods for the direct reaction of alcohol substrates with XCF2CF2X to efficiently generate 2-X-1,1,2,2-tetrafluoroethyl alkyl ether. There are only a few sporadic cases at present:

[0009] The first example is the direct reaction of ethanol with BrCF2CF2Br under the action of potassium hydroxide, which can only obtain the target product CH3CH2OCF2CF2Br with a yield of 31% (J. Fluorine Chem. 1979, 13, 123);

[0010]

[0011] The second example is that an alcohol containing an oxygen atom at the β-position directly reacts with BrCF2CF2Br in DMF under the action of NaH to obtain the target product 2-bromo-1,1,2,2-tetrafluoroethyl ethyl ether with a yield of 88%. However, the structure of the reaction substrate is special, and the β-position of the hydroxyl group must contain an oxygen atom substituent (EP3670501A1, 2006);

[0012]

[0013] The third example is the direct reaction of fluoroalkyl-substituted ethanol with BrCF2CF2Br in DMF under the action of NaH to generate 2-bromo-1,1,2,2-tetrafluoroethyl ether with good to excellent yields. Similarly, the reaction substrate has a special structure and contains fluorine atoms at the β-position of the hydroxyl group (JP2007332060A, 2007);

[0014]

[0015] However, the above conditions are not universal. For example, benzyl alcohol can directly react with BrCF2CF2Br under the action of potassium to obtain 2-bromo-1,1,2,2-tetrafluoroethylated product PhCH2OCF2CF2Br with a yield of only 2.6% (J. Fluorine Chem. 2015, 171, 139).

[0016]

[0017] In addition, we used phenylbutanol as the template substrate and directly reacted it with BrCF2CF2Br in DMF with sodium hydride as the base to give Ph(CH2)4OCF2CF2Br with a yield of only 27%.

[0018]

[0019] It can be seen that, unlike aryl trifluorovinyl ethers, there is currently no universal and practical methodology for ordinary laboratories to synthesize trifluorovinyl alkyl ethers from alcohols. Therefore, it is very important to successfully react alcohols with BrCF2CF2Br to generate 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ethers. This is also the biggest challenge and research focus in the synthesis of trifluorovinyl alkyl ethers from alcohols and BrCF2CF2Br.

[0020] Therefore, the art is in urgent need of providing a safe, efficient and widely applicable method for synthesizing trifluorovinyl ether compounds and 2-halogen-tetrafluoroethyl alkyl ether compounds. Summary of the invention

[0021] The purpose of the present invention is to provide a method for preparing trifluorovinyl ether compounds and intermediates thereof in view of the defect of poor substrate applicability in the existing methods for preparing trifluorovinyl ether compounds and intermediates thereof. Specifically, 1,2-dihalotetrafluoroethane and alcohol molecules are used to synthesize 1,2-dihalotetrafluoroethyl ether compounds, and trifluorovinyl ether compounds are further obtained by dehalogenation. The method of the present invention has cheap and readily available raw materials, mild reaction conditions and simple operation.

[0022] In a first aspect, the present invention provides a method for introducing a 2-halogen-1,1,2,2-tetrafluoroethyl group into an alcohol compound molecule. Specifically, a method for preparing a 2-halogen-1,1,2,2-tetrafluoroethyl ether compound comprises the following steps:

[0023] In an organic solvent, in the presence of an initiator, a sodium salt and / or potassium salt of an alcohol compound containing a fragment as shown in formula I is subjected to an etherification reaction with 1,2-dihalotetrafluoroethane as shown in formula XCF2CF2X to obtain a 2-halogeno-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula II (corresponding to the alcohol compound);

[0024]

[0025] Wherein, X is the halogen, which is independently chlorine or bromine;

[0026] M is sodium or potassium;

[0027] C sp3 It means that the C connected to O is an sp3 hybridized carbon atom.

[0028] The organic solvent may be a conventional organic solvent in this type of reaction in the art, such as an aromatic hydrocarbon solvent, a nitrile solvent, an ether solvent, an ester solvent, an amide solvent, a sulfoxide solvent, or a combination thereof. The aromatic hydrocarbon solvent may be toluene; the nitrile solvent may be acetonitrile and / or benzonitrile; the ether solvent may be one or more of tetrahydrofuran, ethyl ether, ethylene glycol dimethyl ether and methyl tert-butyl ether; the ester solvent may be ethyl acetate; the amide solvent may be N,N-dimethylformamide DMF; the sulfoxide solvent may be dimethyl sulfoxide DMSO. DMF is preferred.

[0029] The initiator can be zinc powder and / or tetrafluoroethylene, preferably zinc powder.

[0030] The 1,2-dihalotetrafluoroethane can be 1,2-dibromotetrafluoroethane, 1,2-dichlorotetrafluoroethane, 1-bromo-2-chlorotetrafluoroethane, or a combination thereof; preferably 1,2-dibromotetrafluoroethane.

[0031] The molar ratio of the sodium salt and / or potassium salt of the alcohol compound to the 1,2-dihalotetrafluoroethane can be a conventional molar ratio in this type of reaction in the art, such as 1:1 to 1:10, preferably 1:3 to 1:4.

[0032] The molar ratio of the sodium salt and / or potassium salt of the alcohol compound to the initiator may be 1:0.01 to 1:1, preferably 1:0.1 to 1:0.5.

[0033] The amount of the organic solvent may not be particularly limited as long as it does not affect the reaction. For example, the molar volume ratio of the alcohol compound to the solvent may be 0.01 mol / L to 1 mol / L, such as 0.1±0.05 mol / L.

[0034] The temperature of the etherification reaction can be a conventional temperature for such reactions in the art, such as -40 to 80°C, preferably, the reaction is carried out at -10 to room temperature (e.g., 10 to 35°C), more preferably, the reaction is carried out at -5 to 0°C for a period of time (e.g., 6 to 10 hours), and then at room temperature.

[0035] It may also include the following post-treatment steps, and the post-treatment operation may be a conventional operation in this type of reaction in the art; for example, after the reaction is completed, an ester solvent is added, quenched, water is added, and the ester solvent is extracted three times, and the organic phases are combined, washed, dried, concentrated, and separated to finally obtain the target product. The ester solvent may be ethyl acetate; the quenching may be quenched by adding a saturated aqueous ammonium chloride solution; the washing may be washed by adding a saturated sodium chloride solution; the drying may be dried by adding anhydrous sodium sulfate; and the separation may be rapid column chromatography separation, for example, silica gel mixing, rapid column chromatography separation with petroleum ether as the eluent.

[0036] The sodium salt and / or potassium salt of the alcohol compound can be prepared by conventional methods in the art.

[0037] In a certain embodiment, the preparation method may also include a preparation method of the sodium salt and / or potassium salt of the alcohol compound, which comprises the following steps: in an organic solvent, subjecting the alcohol compound to a salt-forming reaction with a base to obtain the sodium salt and / or potassium salt of the alcohol compound;

[0038] The base is sodium and / or potassium base.

[0039] The base may be sodium, potassium, NaH, KH, sodium methoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, or a combination thereof; for example, NaH.

[0040] The molar ratio of the alcohol compound to the base may be 1:1 to 1:4, preferably 1:2 to 1:3.

[0041] The organic solvent may be a conventional organic solvent in this type of reaction in the art, such as the organic solvent described in the above etherification reaction, and may be independently the same or different, specifically: an aromatic hydrocarbon solvent, a nitrile solvent, an ether solvent, an ester solvent, an amide solvent, a sulfoxide solvent, or a combination thereof. The aromatic hydrocarbon solvent may be toluene; the nitrile solvent may be acetonitrile and / or benzonitrile; the ether solvent may be one or more of tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, methyl tert-butyl ether and dioxane; the ester solvent may be ethyl acetate; the amide solvent may be DMF; the sulfoxide solvent may be DMSO. DMF is preferred.

[0042] The temperature of the salt-forming reaction can be a conventional temperature for such reactions in the art, such as -40 to 80°C, preferably, -10 to room temperature (such as 10 to 35°C), more preferably, -5 to 0°C.

[0043] Preferably, after the salt-forming reaction is completed, the etherification reaction is directly carried out without any treatment.

[0044] In a certain scheme, the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound can be prepared by a one-pot method using the alcohol compound as a raw material (including the salt-forming reaction and the etherification reaction); for example, it can be the following steps: in the organic solvent, in the presence of the initiator and the base, the alcohol compound is subjected to an etherification reaction with 1,2-dihalotetrafluoroethane to obtain the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound.

[0045] In the present invention, the alcohol compound corresponding to the sodium salt and / or potassium salt of the alcohol compound may include one or more (2, 3, 4, 5 or more) hydroxyl groups selected from the following group: primary hydroxyl groups, secondary hydroxyl groups and tertiary hydroxyl groups.

[0046] In one embodiment, the sodium salt and / or potassium salt of the alcohol compound is represented by the formula R-OM, and the corresponding 2-halogen-1,1,2,2-tetrafluoroethyl ether compound is represented by the formula R-OCF2CF2X.

[0047] Wherein, the definition of X is as shown above;

[0048] R- is selected from the group consisting of: Substituted or unsubstituted C3-C 30 Cycloalkyl, substituted or unsubstituted 3-30-membered heterocycloalkyl; wherein the 3-30-membered heterocycloalkyl in the substituted or unsubstituted 3-30-membered heterocycloalkyl has 1-6 heteroatoms or heteroatom groups selected from O, N, S, S(═O) and S(═O)2; R y1 , R y2 , R y3 are independently: D, substituted or unsubstituted C1-C 30 Alkyl, substituted or unsubstituted C2-C 30 Alkenyl, substituted or unsubstituted C2-C 30 Alkynyl, substituted or unsubstituted C3-C 30 Cycloalkyl, substituted or unsubstituted 3-30 membered heterocycloalkyl; substituted or unsubstituted C6-C 30 The substituted or unsubstituted 3-30-membered heterocycloalkyl group has 1-6 heteroatoms or heteroatom groups selected from O, N, S, S(═O)2; the substituted or unsubstituted 5-30-membered heteroaryl group has 1-6 heteroatoms selected from O, N and S;

[0049] The substitution refers to the replacement of one or more hydrogen atoms (e.g., 1 to 4) on the group by a substituent R z Replace, each R z are independently: D, halogen, nitro, cyano, oxo (=O), thio (=S), -OH, -NH2, -COOH, -CHO, 1 or 2 substituted or unsubstituted C1-C 20 Alkyl-substituted amino, substituted or unsubstituted C1-C 20 Alkyl, substituted or unsubstituted C2-C 20 Alkenyl, substituted or unsubstituted C2-C 20 Alkynyl, substituted or unsubstituted C3-C 20Cycloalkyl, substituted or unsubstituted 3-20 membered heterocycloalkyl; substituted or unsubstituted C6-C 20 aryl, substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted C1-C 20 Alkyl-substituted amino-Y-, substituted or unsubstituted C1-C 20 Alkyl-Y-, substituted or unsubstituted C2-C 20 Alkenyl-Y-, substituted or unsubstituted C2-C 20 Alkynyl-Y-, substituted or unsubstituted C3-C 20 Cycloalkyl-Y-, substituted or unsubstituted 3-20 membered heterocycloalkyl-Y-, substituted or unsubstituted C6-C 20 wherein each Y- is independently: O-, S-, S(O)-, S(O)2-, Se-, Te-, S(O)2O-, C(O)-, OC(O)-, C(O)O-, NHC(O)-; the substituted or unsubstituted 3-20-membered heterocycloalkyl, the 3-20-membered heterocycloalkyl in the substituted or unsubstituted 3-20-membered heterocycloalkyl-Y- has 1-5 heteroatoms or heteroatom groups selected from O, N, S, S(=O)2; the substituted or unsubstituted 5-20-membered heteroaryl, the 5-20-membered heteroaryl in the substituted or unsubstituted 5-20-membered heteroaryl-Y- has 1-5 heteroatoms selected from O, N and S;

[0050] The substituent R z The substitution on R z One or more hydrogen atoms (e.g., 1 to 4) on the x Replace, each R x are independently: D, halogen, nitro, cyano, oxo (=O), thio (=S), -OH, -NH2, -COOH, -CHO, 1 or 2 C1-C 10 Alkyl substituted amino, halogenated or oxo or unsubstituted C1-C 10 Alkyl, halogenated or unsubstituted C2-C 10 Alkenyl, halogenated or unsubstituted C2-C 10 Alkynyl, halogenated or oxo or unsubstituted C3-C 10 Cycloalkyl, halogenated or oxo-substituted or unsubstituted 3-10 membered heterocycloalkyl; halogenated or unsubstituted C6-C 10 aryl, halogenated or unsubstituted 5-10 membered heteroaryl, 1 or 2 C1-C 10 Alkyl-substituted amino-Z-, halogenated or unsubstituted C1-C 10 Alkyl-Z-, halogenated or unsubstituted C2-C 10Alkenyl-Z-, halogenated or unsubstituted C2-C 10 Alkynyl-Z-, halogenated or unsubstituted C3-C 10 Cycloalkyl-Z-, halogenated or unsubstituted 3-10 membered heterocycloalkyl-Z-, halogenated or unsubstituted C6-C 10 wherein each Z- is independently: C1-C6 alkylene, O-, S-, S(O)-, S(O)2-, Se-, Te-, S(O)2O-, C(O)-, OC(O)-, C(O)O-, NHC(O)-; the substituted or unsubstituted 3-10 membered heterocycloalkyl, the 3-10 membered heterocycloalkyl in the substituted or unsubstituted 3-10 membered heterocycloalkyl-Z- has 1-4 heteroatoms or heteroatom groups selected from O, N, S, S(=O) and S(=O)2; the substituted or unsubstituted 5-10 membered heteroaryl, the 5-10 membered heteroaryl in the substituted or unsubstituted 5-10 membered heteroaryl-Z- has 1-4 heteroatoms selected from O, N and S.

[0051] In a certain embodiment of the present invention, in the alcohol compound corresponding to the sodium salt and / or potassium salt of the alcohol compound, the β position of the alcohol hydroxyl group is not directly substituted by O, S or F.

[0052] The 2-halogen-1,1,2,2-tetrafluoroethyl ether compound is any one of the following:

[0053]

[0054]

[0055] In a second aspect of the present invention, a method for synthesizing trifluorovinyl ether compounds from 2-halo-1,1,2,2-tetrafluoroethyl ether compounds is provided. Specifically, a method for preparing trifluorovinyl ether compounds comprises the following steps:

[0056] In an organic solvent, in the presence of an initiator, a 2-halogeno-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula III and a reducing agent are subjected to a dehalogenation reaction to obtain a trifluorovinyl ether compound containing a fragment as shown in formula IV; the initiator is: zinc salt, water, or a combination thereof;

[0057]

[0058] Wherein, X is the halogen, which is independently chlorine or bromine.

[0059] The organic solvent may be a conventional organic solvent in this type of reaction in the art, such as an aromatic hydrocarbon solvent, a nitrile solvent, an ether solvent, an ester solvent, an alcohol solvent, an amide solvent, a sulfoxide solvent, or a combination thereof. The aromatic hydrocarbon solvent may be toluene; the nitrile solvent may be acetonitrile and / or benzonitrile; the ether solvent may be one or more of tetrahydrofuran, ethyl ether, ethylene glycol dimethyl ether, methyl tert-butyl ether and dioxane; the ester solvent may be ethyl acetate; the alcohol solvent may be one or more of methanol, ethanol, isopropanol and tert-butyl alcohol; the amide solvent may be DMF; the sulfoxide solvent may be DMSO. Acetonitrile is preferred.

[0060] The zinc salt can be zinc chloride, zinc acetate, or a hydrate thereof.

[0061] The initiator can be zinc chloride, zinc acetate dihydrate or water.

[0062] When the initiator is a zinc salt or a hydrate thereof, the molar ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the initiator may be 1:0.01 to 1:10, preferably 1:(0.3±0.1). When the initiator is water, the molar ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the initiator may be 1:(10±1).

[0063] The reducing agent may be a conventional reducing agent in this type of reaction in the art, such as zinc powder, iron powder or a combination thereof; for example, zinc powder.

[0064] The molar ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the reducing agent can be a conventional molar ratio in this type of reaction in the art, such as 1:1 to 1:10, such as 1:(1.5±0.2).

[0065] The amount of the organic solvent may not be particularly limited as long as it does not affect the reaction. For example, the molar volume ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the organic solvent may be 0.01 mol / L to 0.5 mol / L, such as 0.05±0.05 mol / L.

[0066] The temperature of the dehalogenation reaction can be a conventional temperature for such reactions in the art, such as room temperature to 120°C, preferably, 40 to 100°C, such as 95°C±5°C.

[0067] In the present invention, it may also include the following post-treatment steps, and the post-treatment operation may be a conventional operation in this type of reaction in the art; for example, after the reaction is completed, the product is concentrated and separated to finally obtain the target product. The separation may be column chromatography separation, for example, silica gel mixing and rapid column chromatography separation using petroleum ether as an eluent.

[0068] In the present invention, in the 2-halo-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula III and the corresponding trifluorovinyl ether compound containing a fragment as shown in formula IV, the C connected to the -O- shown can be a sp, sp2, or sp3 hybridized carbon atom, such as a C atom in an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, or heteroaryl group; that is, the group connected to the -O- shown is a hydrocarbon group (including an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl) or an aromatic hydrocarbon group (including an aryl or heteroaryl group).

[0069] In a certain embodiment of the present invention, when the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula III and the corresponding trifluorovinyl ether compound containing a fragment as shown in formula IV, the C connected to -O- is a C atom in an aromatic group, and the aromatic group may be a substituted or unsubstituted C6-C 30 The substitution refers to the substitution of one or more hydrogen atoms on the aryl group by a substituent R a Replace, each R a are independently: halogen, cyano, -OH, -NH2, 1 or 2 substituted or unsubstituted C1-C 20 Alkyl-substituted amino, substituted or unsubstituted C1-C 20 Alkyl, substituted or unsubstituted C2-C 20 Alkenyl, substituted or unsubstituted C2-C 20 Alkynyl, substituted or unsubstituted C3-C 20 Cycloalkyl, substituted or unsubstituted 3-20 membered heterocycloalkyl; substituted or unsubstituted C6-C 20 aryl, substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted C1-C 20 Alkyl-substituted amino-M-, substituted or unsubstituted C1-C 20 Alkyl-M-, substituted or unsubstituted C2-C 20 Alkenyl-M-, substituted or unsubstituted C2-C 20 Alkynyl-M-, substituted or unsubstituted C3-C 20 Cycloalkyl-M-, substituted or unsubstituted 3-20 membered heterocycloalkyl-M-, substituted or unsubstituted C6-C 20wherein M- is independently: O-, S-, S(O)2-, S(O)2O-, OC(O)-, C(O)O-, NHC(O)-; the substituted or unsubstituted 3-20-membered heterocycloalkyl, the 3-20-membered heterocycloalkyl in the substituted or unsubstituted 3-20-membered heterocycloalkyl-M- has 1-5 heteroatoms or heteroatom groups selected from O, N, and S; the substituted or unsubstituted 5-20-membered heteroaryl, the 5-20-membered heteroaryl in the substituted or unsubstituted 5-20-membered heteroaryl-M- has 1-5 heteroatoms selected from O, N, and S; the substituent R a The substitution on R a One or more hydrogen atoms on the z Replacement, where R z The definition of is as mentioned above.

[0070] In a certain embodiment of the present invention, the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound containing the fragment shown in formula III can be represented by the formula R-OCF2CF2X as described above.

[0071] In a certain scheme of the preparation method of the trifluorovinyl ether compound, it may include the preparation method of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound, and the operation and reaction conditions of the preparation method of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound may be as shown by the operation and reaction conditions described in any scheme of the preparation method of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound as described above.

[0072] In a third aspect, the present invention further provides a 2-halogen-1,1,2,2-tetrafluoroethyl ether compound,

[0073] It is shown in the formula R'-OCF2CF2X,

[0074] Wherein, X is defined as above; R' is defined as R;

[0075] And the formula R'-OCF2CF2X is not the following compound:

[0076] CH3OCF2CF2Br, CF3(CF2)7CH2OCF2CF2Br, BrCF2CF2OCH2CF2OCF2CF2OCF2CF2OCF2CF2CF2CF3, BrCF2CF2OCH(Me)CH2CH2CH(Me)OCF2CF2H, BrCF2CF2 OCH(Me)CH2CH2CH(Me)OCF2CF2Br, BrCF2CF2OCH(Me)CH2CH2CH2CH2CH(Me)OCF2CF2H, BrCF2CF2OC(CF3)3, BrCF2CF2OC(CF3)2CF2CF3 CH3OCF2CF2CI, CF3CH2OCF2CF2Cl, NO2CF2CH2OCF2CF2Cl, CICF2CF2OCH2(CF2)2CF2H, CICF2CF2OCH2(C F2)5CF2H, CICF2CF2OCH(CF3)2, CICF2CF2OC(CH3)3, CICF2CF2OC(CF3)3, CICF2CF2OCH2CF2CF2CF=CF2.

[0077] Specifically, the 2-halogen-1,1,2,2-tetrafluoroethyl alkyl ether compound is any of the following compounds:

[0078]

[0079] In the fourth aspect of the present invention, there is also provided an application of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound as described above in the preparation of trifluorovinyl ether compounds; wherein the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound is represented by the formula R'-OCF2CF2X as described above.

[0080] In one embodiment of the application, the steps include:

[0081] In an organic solvent, in the presence of an initiator, the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound and a reducing agent are subjected to a dehalogenation reaction to obtain a trifluorovinyl ether compound as shown in formula V; the initiator is: zinc salt, water, or a combination thereof;

[0082]

[0083] The operation and reaction conditions of the dehalogenation reaction may be as shown in the operation and reaction conditions of the preparation method of trifluorovinyl alkyl ether described above.

[0084] Unless otherwise indicated, the following definitions used herein shall apply. For purposes of the present invention, chemical elements are consistent with the Periodic Table of the Elements, CAS version, and Handbook of Chemistry and Physics, 75th edition, 1994. In addition, general principles of organic chemistry can be found in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry" by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007, the entire contents of which are incorporated herein by reference.

[0085] In this specification, groups and substituents thereof can be selected by those skilled in the art to provide stable structural moieties and compounds. When substituents are described by conventional chemical formulas written from left to right, the substituents also include chemically equivalent substituents obtained when the structural formula is written from right to left.

[0086] Certain chemical groups defined herein are preceded by simplified notations to indicate the total number of carbon atoms present in the group. For example, a C1-C6 alkyl group refers to an alkyl group as defined below having a total of 1, 2, 3, 4, 5, or 6 carbon atoms. The total number of carbon atoms in the simplified notation does not include carbons that may be present in substituents of the group.

[0087] As used herein, numerical ranges defined in substituents such as 0 to 4, 1-4, 1 to 3, etc. indicate integers within the range, such as 1-6 is 1, 2, 3, 4, 5, 6.

[0088] In addition to the foregoing, when used in the specification and claims of the present application, the following terms have the meanings indicated below unless otherwise specifically stated.

[0089] The term "comprising" is an open expression, that is, including the contents specified in the present invention but not excluding other contents.

[0090] The term "substituted" means that any one or more hydrogen atoms on a particular atom are replaced by a substituent as long as the valence state of the particular atom is normal and the compound after the substitution is stable.

[0091] In general, the term "substituted" means that one or more hydrogen atoms in a given structure are replaced by a specific substituent. Further, when the group is substituted by more than one substituent, the substituents are independent of each other, that is, the more than one substituent may be different from each other or the same. Unless otherwise indicated, a substituent group may be substituted at each substitutable position of the substituted group. When more than one position in the given structural formula can be substituted by one or more substituents selected from a specific group, the substituents may be substituted at each position in the same or different manner. When a substituent group and a substituted group are both cyclic structures, the substitution may be that the substituent group is connected to the substituted group by a single bond, or that the substituent group is connected to the substituted group by a ring.

[0092] In various parts of this specification, substituents of compounds disclosed in the present invention are disclosed according to group types or ranges. It is particularly pointed out that the present invention includes each independent subcombination of the individual members of these group types and ranges. The term "C x -C y "Alkyl" refers to a straight or branched chain saturated hydrocarbon containing x to y carbon atoms. For example, the term "C1-C6 alkyl" or "C 1-6 "Alkyl" specifically refers to methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl and C6 alkyl disclosed independently; "C 1-4 The term "alkyl" specifically refers to the independently disclosed methyl, ethyl, C3 alkyl (i.e. propyl, including n-propyl and isopropyl), C4 alkyl (i.e. butyl, including n-butyl, isobutyl, sec-butyl and tert-butyl).

[0093] As used herein, the terms "part", "moiety", "chemical moiety", "group", "chemical group" refer to a specific fragment or functional group in a molecule. A chemical moiety is generally considered to be a chemical entity embedded in or attached to a molecule.

[0094] When a substituent is listed without indicating the atom through which it is attached to a chemical formula (including but not specifically mentioned compounds), such a substituent may be bonded via any atom thereof. Combinations of substituents and / or their variants are permitted only if such combinations result in stable compounds.

[0095] When any variable (such as R z ) appears multiple times in the definition of a compound, the definition of the variable at each position is independent of the definition of the other positions, and their meanings are independent of each other and do not affect each other. z group-substituted, that is, the group may be replaced by up to 3 R z Replace, the position R z Definition and other positions Rz In addition, combinations of substituents and / or variables are permissible only if such combinations result in stable compounds.

[0096] When there is no explicit indication that a group has a substituent, such group refers only to unsubstituted groups. For example, when "C1-C4 alkyl" is not preceded by "substituted or unsubstituted", it only refers to "C1-C4 alkyl" itself or "unsubstituted C1-C4 alkyl".

[0097] In various parts of the present invention, linking substituents are described. When the structure clearly requires a linking group, the Markush variable listed for that group should be understood as a linking group. For example, if the structure requires a linking group and the Markush group definition for that variable lists "alkyl", it should be understood that the "alkyl" represents a linked alkylene group.

[0098] In some specific structures, when an alkyl group is clearly indicated as a linking group, the alkyl group represents a linked alkylene group, for example, the C1-C6 alkyl in the group "halo-C1-C6 alkyl" should be understood as a C1-C6 alkylene.

[0099] The term "halogen" refers to fluorine, chlorine, bromine or iodine, in particular to F or Cl.

[0100] The term "ether" refers to a product in which the hydrogen of the hydroxyl group of an alcohol or phenol is replaced by a hydrocarbon group (including an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocycloalkyl group) or an aromatic hydrocarbon group (including an aryl group or a heteroaryl group).

[0101] In the present application, as a group or part of other groups (for example, in haloalkyl, deuterated alkyl and the like), the term "alkyl" refers to a saturated aliphatic hydrocarbon group including branched and straight chains with a specified number of carbon atoms, consisting only of carbon atoms and hydrogen atoms, and connected to the rest of the molecule by a single bond. For example, it has 1 to 30 (preferably 1 to 20, more preferably 1 to 10, more preferably 1 to 6) carbon atoms; wherein propyl is C3 alkyl (including isomers, such as n-propyl or isopropyl); butyl is C4 alkyl (including isomers, such as n-butyl, sec-butyl, isobutyl or tert-butyl); pentyl is C5 alkyl (including isomers, such as n-pentyl, 1-methyl-butyl, 1-ethyl-propyl, 2-methyl-1-butyl The hexyl group is a C6 alkyl group (including isomers, such as n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl). For example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 2-methylbutyl, 2,2-dimethylpropyl, n-hexyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, n-octyl, nonyl, decyl and the like.

[0102] In the present application, as a group or part of other groups, the term "alkylene" means a saturated divalent hydrocarbon group obtained by removing two hydrogen atoms from a saturated straight or branched hydrocarbon group; that is, one hydrogen in an alkyl group is replaced, and the definition of alkyl group is as described above. Examples of alkylene groups include methylene (-CH2-), ethylene {including-CH2CH2- or-CH(CH3)-}, isopropylene {including-CH(CH3)CH2- or-C(CH3)2-}, and the like.

[0103] In the present application, as a group or part of other groups, the term "alkenyl" refers to a straight or branched hydrocarbon chain radical having a specified number of carbon atoms, including at least one double bond, consisting only of carbon atoms and hydrogen atoms, and connected to the rest of the molecule by a single bond. For example, having 2 to 30 (preferably 2 to 20, more preferably 2 to 10, most preferably 2 to 6) carbon atoms, such as but not limited to vinyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, sec-butenyl, tert-butenyl, n-pentenyl, 2-methylbutenyl, 2,2-dimethylpropenyl, n-hexenyl, heptenyl, 2-methylhexenyl, 3-methylhexenyl, octenyl, nonenyl and decenyl, etc.

[0104] In the present application, as a group or as part of other groups, the term "alkynyl" refers to a straight or branched hydrocarbon chain radical having a specified number of carbon atoms, including at least one triple bond, consisting only of carbon atoms and hydrogen atoms, and connected to the rest of the molecule by a single bond. For example, having 2 to 30 (preferably 2 to 20, more preferably 2 to 10, most preferably 2 to 8) carbon atoms; for example, including but not limited to ethynyl, n-propynyl, isopropynyl, n-butynyl, isobutynyl, sec-butynyl, tert-butynyl, n-pentynyl, 2-methylbutynyl, 2,2-dimethylpropynyl, n-hexynyl, heptynyl, 2-methylhexynyl, 3-methylhexynyl, octynyl, nonynyl and decynyl, etc.

[0105] In the present application, as a group or part of other groups, the term "cycloalkyl" means a saturated monocyclic or polycyclic (e.g., bicyclic, tricyclic or more cyclic bridged ring, fused ring or spirocyclic system) carbocyclic substituent with a specified number of carbon atoms, and which can be connected to the rest of the molecule by a single bond via any suitable carbon atom. For example, a 3-30-membered cycloalkyl having 3 to 30 carbon atoms, preferably a 3-20-membered cycloalkyl having 3 to 20 carbon atoms, more preferably a 3-10-membered cycloalkyl having 3 to 10 carbon atoms, and most preferably a 3-6-membered cycloalkyl having 3 to 6 carbon atoms. In a certain embodiment, a typical monocyclic cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or adamantyl. For the purpose of the present invention, "cycloalkyl" can also be fused with an aryl or heteroaryl as defined herein, provided that the cycloalkyl is connected to the rest of the molecule by a single bond via an atom on the cycloalkyl ring.

[0106] In the present application, the term "cycloalkenyl" as a group or part of another group means a cyclic hydrocarbon group having a specified number of carbon atoms, having at least one double bond (such as a carbon-carbon double bond), a monocyclic or polycyclic (e.g., a bicyclic, tricyclic or more cyclic bridged ring, a fused ring or a spirocyclic system), and which can be connected to the rest of the molecule by a single bond via any suitable carbon atom. For example, it has 3 to 30 carbon atoms, preferably 3 to 20 carbon atoms, and more preferably 3 to 10 carbon atoms. For the purposes of the present invention, "cycloalkenyl" can also be fused to an aryl or heteroaryl group as defined herein, provided that the cycloalkenyl group is connected to the rest of the molecule by a single bond via an atom on the cycloalkenyl ring.

[0107] In the present application, as a group or part of other groups, the term "heterocycloalkyl" refers to a stable saturated monocyclic or polycyclic (e.g., bicyclic, tricyclic or more cyclic bridged, fused or spirocyclic) heterocyclic hydrocarbon group having at least one carbon atom and a specified number of heteroatoms or heteroatoms, and which can be connected to the rest of the molecule through any suitable carbon atom or heteroatom by a single bond. For example, a stable 3- to 30-membered (preferably 3- to 20-membered, more preferably 3- to 10-membered, most preferably 3- to 7-membered) saturated heterocyclic hydrocarbon group consisting of 2 to 29 carbon atoms (preferably 2 to 19-membered, more preferably 2 to 9-membered, most preferably 2 to 6-membered) and 1 to 6 heteroatoms or heteroatom groups selected from N, O, S, S(=O) and S(=O)2, preferably a 4- to 10-membered saturated monocyclic or polycyclic (e.g., bicyclic, tricyclic or more cyclic bridged, fused or spirocyclic) heterocyclic hydrocarbon group containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, S(=O) and S(=O)2. The ring system of the heterocycloalkyl bicyclic ring may include one or more heteroatoms in one or both rings; and is saturated. For purposes of this invention, "heterocycloalkyl" may also be fused to an aryl or heteroaryl group as defined herein, provided that the heterocycloalkyl is attached to the rest of the molecule by a single bond through an atom on the heterocycloalkyl ring.

[0108] In the present application, as a group or part of other groups, the term "heterocycloalkenyl" refers to a stable unsaturated non-aromatic monocyclic or polycyclic (e.g., bicyclic, tricyclic or more cyclic bridged, fused or spirocyclic) heterocycloalkenyl having at least one carbon-carbon double bond and a specified number of heteroatoms or heteroatom groups, and which can be connected to the rest of the molecule through any suitable carbon atom or heteroatom by a single bond. For example, a stable 3- to 30-membered (preferably 3- to 20-membered, more preferably 3- to 10-membered, most preferably 3- to 7-membered) unsaturated non-aromatic heterocycloalkenyl group consisting of 2 to 29 carbon atoms (preferably 2 to 19-membered, more preferably 2 to 9-membered, most preferably 2 to 6-membered) and 1 to 6 heteroatoms or heteroatom groups selected from N, O, S, S(=O) and S(=O)2, preferably a 4- to 10-membered unsaturated non-aromatic monocyclic or polycyclic (e.g., bicyclic, tricyclic or more cyclic bridged, fused or spirocyclic) heterocycloalkenyl group containing 1, 2, 3 or 4 heteroatoms or heteroatom groups independently selected from N, O, S, S(=O) and S(=O)2. The bicyclic ring system of the heterocycloalkenyl group may include one or more heteroatoms in one or both rings; and contains at least one olefinic bond. For purposes of this invention, "heterocyclenyl" may also be fused to an aryl or heteroaryl group as defined herein, provided that the heterocyclenyl group is attached to the rest of the molecule by a single bond through an atom on the heterocyclenyl ring.

[0109] In the present application, as a group or part of other groups, the term "aryl" means a conjugated hydrocarbon ring system group having a specified number of carbon atoms and satisfying the 4n+2 rule. For example, a conjugated hydrocarbon ring system group having 6 to 30 carbon atoms (preferably having 6 to 20 carbon atoms, more preferably having 6 to 10 carbon atoms) that satisfies the 4n+2 rule. For the purposes of the present invention, aryl can be a monocyclic, bicyclic, tricyclic or more ring system, and can also be fused with a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl as defined herein, provided that the aryl is connected to the rest of the molecule via a single bond via an atom on the aromatic ring. Examples of aryl include, but are not limited to, phenyl, naphthyl, anthracenyl, phenanthrenyl or fluorenyl.

[0110] In the present application, as a group or part of other groups, the term "heteroaryl" means a stable conjugated heterocyclic ring system group that satisfies the 4n+2 rule and has a specified number of carbon atoms and a specified number of heteroatoms in the ring. For example, a 5- to 30-membered (preferably 5- to 20-membered, more preferably 5- to 10-membered) conjugated ring system group having 1 to 29 carbon atoms (preferably 1 to 19 carbon atoms, more preferably 1 to 9 carbon atoms) and 1 to 6 heteroatoms selected from nitrogen, oxygen and sulfur. Unless otherwise specifically indicated in this specification, the heteroaryl group can be a monocyclic, bicyclic, tricyclic or more cyclic ring system, and can also be fused with a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl group as defined above, provided that the heteroaryl group is connected to the rest of the molecule via atoms on the aromatic ring by a single bond. Examples of heteroaryl groups include, but are not limited to, thienyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, diazolyl, oxadiazolyl, isoxazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, benzimidazolyl, benzopyrazolyl, indolyl, furanyl, pyrrolyl, triazolyl, tetrazolyl, triazinyl, indolizinyl, isoxazolyl, thiadiazolyl, isoindolyl, indazolyl, isoindazolyl, purinyl, quinolyl, isoquinolyl, naphthazinyl, naphthyridinyl, quinoxalinyl, pteridinyl, carbazolyl, carbolinyl, phenanthridinyl, phenanthrolinyl, acridinyl, phenazinyl, isothiazolyl, benzothiazolyl, benzisothiazolyl, benzothienyl, oxatotriazolyl, cinnolinyl, quinazolinyl, o-phenanthroline, isoxazolyl, phenoxazinyl, phenothiazinyl, or benzoxazolyl.

[0111] It should be understood that as used herein, the singular forms, such as "a," and "an," include plural references unless otherwise specified.

[0112] The term "one or more" or "one or more than two" means 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.

[0113] Unless otherwise specified, the present invention adopts conventional methods of mass spectrometry and elemental analysis, and each step and condition can refer to conventional operating steps and conditions in the art.

[0114] Unless otherwise indicated, the present invention adopts standard nomenclature and standard laboratory procedures and techniques of analytical chemistry, organic synthetic chemistry and optics. In some cases, standard techniques are used for chemical synthesis, chemical analysis, and light emitting device performance testing.

[0115] In addition, it should be noted that, unless otherwise explicitly stated, the description method "... independently are" used in the present invention should be understood in a broad sense, meaning that the individuals described are independent of each other and can independently be the same or different specific groups. In more detail, the description method "... independently are" can mean that in different groups, the specific options expressed by the same symbols do not affect each other; it can also mean that in the same group, the specific options expressed by the same symbols do not affect each other.

[0116] Those skilled in the art will appreciate that, according to the conventions used in the art, the structural formulas used in this application to describe groups and It means that the corresponding group R is connected to other fragments and groups in the compound through this site.

[0117] Unless otherwise specified, all technical and scientific terms used herein have the standard meaning in the field to which the claimed subject matter belongs. If there are multiple definitions for a term, the definition herein shall prevail.

[0118] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0119] The reagents and raw materials used in the present invention are commercially available.

[0120] The positive progressive effects of the present invention are: 1. The present invention provides a new method for synthesizing 2-halogen-1,1,2,2-tetrafluoroethyl ether compounds and trifluorovinyl alkyl ether compounds with high efficiency and wide versatility. Various alcohols can be conveniently converted into 2-halogen-1,1,2,2-tetrafluoroethyl ether compounds and further converted into trifluorovinyl alkyl ether compounds by the method of the present invention. The method of the present invention has good compatibility of substrate functional groups and little effect on other functional groups of the substrate, which can further expand the substrate range, improve the yield and reduce the cost.

[0121] 2. This method has mild reaction conditions, safe operation, fast reaction speed, high yield, and does not require the use of explosive substances. It is very suitable for industrial production. The obtained product has great application potential in biomedicine, pesticides and materials science. DETAILED DESCRIPTION

[0122] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples. The experimental methods in the following examples without specifying specific conditions are carried out according to conventional methods and conditions, or selected according to the product specifications.

[0123] In the present invention, room temperature refers to ambient temperature, which is 10°C-35°C.

[0124] Before conducting the experimental research, we first explored why phenolic substrates can react well with BrCF2CF2Br under the action of base to generate 2-bromo-1,1,2,2-tetrafluoroethyl aryl ether, but it is more difficult for alcohols to react with BrCF2CF2Br.

[0125] In 1982, Wakselman and Rico reported the first case that thiophenol and potassium salt of phenol can react with BrCF2CF2Br to generate the corresponding 2-bromo-1,1,2,2-tetrafluoroethyl aryl (thio) ether. It was specifically mentioned that potassium salt of phenol cannot react spontaneously with BrCF2CF2Br and needs a small amount of thiol to initiate the reaction (J. Fluorine Chem. 1982, 20, 759).

[0126] ArXK+BrCF2CF2Br→ArXCF2CF2Br

[0127] X=O,S

[0128] The authors proposed the following ionic chain reaction mechanism: As to why potassium phenolate requires an initiator to react, the authors believe that this is because the phenol anion is too "hard" compared to the thiophenol anion, and cannot attack BrCF2CF2Br smoothly during the initiation stage of the reaction, causing the reaction to fail to proceed spontaneously.

[0129] Initiation:RS - +BrCF2CF2Br→RSBr+-CF2CF2Br

[0130] Propagation: - CF2CF2Br→CF2=CF2+Br -

[0131] ArX - +CF2=CF2→ArXCF2CF 2-

[0132] ArXCF2CF2 - +BrCF2CF2Br→ArXCF2CF2Br+ - CF2CF2Br

[0133] termination: ArXCF2CF2 - +″H″[solvent]→ArXCF2CF2H

[0134] Subsequently, in 1984, Jiang Xikui et al. corrected the conclusion of Wakselman and Rico and found that potassium phenolate can spontaneously react with BrCF2CF2Br to generate 2-bromo-1,1,2,2-tetrafluoroethyl aryl ether, and the reaction can also be extended to more dibromoperfluoroalkyl groups (Tetrahedron Lett. 1984, 25, 4937). The author reported that this reaction can be carried out in a variety of solvents, as long as the potassium salt and BrCF2CF2Br are carefully purified and dried, a higher yield than before can be obtained without an initiator. They also proposed an anionic chain reaction mechanism, believing that the phenolate anion can initiate the reaction by nucleophilic attack on the bromine atom in BrCF2CF2Br, as shown below:

[0135] Initiation: Aro - +BrCF2CF2Br→ArOBr+ - CF2CF2Br

[0136] Propagation: - CF2CF2Br→CF2=CF2+Br -

[0137] AO - +CF2=CF2→ArOCF2CF2 -

[0138]

[0139]

[0140] In 2007, Li et al. further revealed the experimental details of the reaction of phenol with BrCF2CF2Br (Tetrahedron Lett. 2007, 48, 7516). Based on the previous work, the reaction conditions were further optimized, and cesium carbonate was used as a base to achieve the efficient preparation of 2-bromo-1,1,2,2-tetrafluoroethyl aryl ether by the reaction of phenol with BrCF2CF2Br. Previously, the raw materials needed to be carefully purified, especially potassium phenolate, which needed to be dried, otherwise the reaction yield would drop significantly. Since potassium phenolate easily absorbs water, the authors adopted the method of preparing potassium phenolate in situ, and found that cesium carbonate could significantly shorten the reaction time and increase the yield by screening the base. Finally, the authors also proposed the anion chain reaction mechanism, and also believed that the SRN1 mechanism involving single electron transfer could not be completely ruled out.

[0141]

[0142] In summary, it can be found that the reason why phenol can react well with BrCF2CF2Br to generate 2-bromo-1,1,2,2-tetrafluoroethyl aryl ether under the action of alkali is that the phenol oxygen anion can successfully initiate the reaction. For alcohol, the alcohol oxygen anion is difficult to attack the bromine atom in BrCF2CF2Br with nucleophilicity and cannot successfully initiate the reaction, making the reaction of alcohol with BrCF2CF2Br particularly difficult. In order to solve the difficulty of the reaction between alcohol and BrCF2CF2Br, we explored and tried to add various initiators to the system to promote the reaction.

[0143] Example 1

[0144] First, a catalytic amount of tetrafluoroethylene (12.5 mol%) was introduced to promote the reaction, and Ph(CH2)4OCF2CF2Br was obtained in a yield of 34%. Compared with the reaction without the additive, the yield of Ph(CH2)4OCF2CF2Br was indeed improved.

[0145]

[0146] Under nitrogen protection, weigh (2mmol, 1.0equiv) was placed in a 25-mL sealed tube, anhydrous DMF (5mL) was added, and then NaH (101mg, 95% purity, 4.0mmol, 2.0equiv) was slowly added. After stirring at room temperature for 6 hours, 1,2-dibromotetrafluoroethane (1.04g, 4.0mmol, 2.0equiv) was added. After stirring for 5 to 10 minutes, tetrafluoroethylene (0.25mmol) was introduced at -78°C. After sealing, the temperature was raised to 60°C for reaction for 12 hours, and ethyl acetate was added for dilution. Trifluorotoluene was used as the internal standard. The yield was 34% as determined by fluorine spectrum.

[0147] Example 2-37 Typical operation of synthesizing 2-bromo-1,1,2,2-tetrafluoroethyl ether from alcohol

[0148]

[0149] Under nitrogen protection, alcohol (0.5mmol, 1.0equiv) and zinc powder (3.3mg, 0.05mmol, 0.1equiv) were weighed in a 25mL sealed tube, anhydrous DMF (5mL) was added, and NaH (25.2mg, 95% purity, 1.0mmol, 2.0equiv) was slowly added. After stirring at room temperature for 4 hours, 1,2-dibromotetrafluoroethane (389.7mg, 1.5mmol, 3.0equiv) was added. After stirring for 5 to 10 minutes, the mixture was stirred at -5 to 0°C for 6 hours. After returning to room temperature, the reaction was continued at room temperature for 12 hours, ethyl acetate was added for dilution, saturated ammonium chloride aqueous solution was added for quenching, water was added, and ethyl acetate was extracted three times. The organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated, mixed with silica gel, and separated by rapid column chromatography with petroleum ether as eluent to finally obtain the target product.

[0150]

[0151] a Reaction conditions: ROH (0.5 mmol, 1.0 eq.) BrCF2CF2Br (1.5 mmol, 3.0 eq.), NaH (1.0 mmol, 2.0 eq.) and Zn (0.05 mmol, 0.1 eq.) in DMF (5 mL). Isolated yield. b The yields in brackets are given by 19 F NMR was measured with PhCF3 as the internal standard.

[0152] It can be seen that whether it is primary alcohol, secondary alcohol, or tertiary alcohol, it can react with BrCF2CF2Br to generate the corresponding bromotetrafluoroethyl alkyl ether with moderate to good yields. For primary alcohols, the reaction yield of alcohols with longer chains is relatively high, among which the yield of benzyl alcohol is relatively low, but the yield of electron-rich benzyl alcohol is slightly higher. For secondary and tertiary alcohols, their overall yields are higher than those of primary alcohols. Whether they are linear or cyclic secondary and tertiary alcohols, they can react well and give good yields.

[0153] Example 2

[0154] The specific compound prepared in Example 2 is

[0155] The substrate was alcohol, and 132.3 mg of colorless oily liquid was obtained with a yield of 83%. 1H NMR (400MHz, CDCl3) δ7.29 (dd, J=8.7, 7.4Hz, 2H), 6.97 (t, J=7.4Hz, 1H), 6.91 ( dd,J=8.7,1.0Hz,2H), 4.34(dd,J=5.8,4.0Hz,2H), 4.21(dd,J=5.7,4.0Hz,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 4.8Hz, 2F), -89.1 (t, J = 4.8Hz, 2F). 13 C NMR (101MHz, CDCl3) δ158.4, 129.7, 121.6, 117.0 (tt, J = 272.0, 31.8Hz), 114. 9,113.8(tt,J=312.4,45.5Hz),65.7,64.2(t,J=5.1Hz).MS(EI,m / z,%):316(M + ,95.67),318(M + +2,100),94(98.9),77(83.26),107(69.12),181(60.58).HRMS(EI):m / z Calcd.for C 10 H9O2BrF4(M)315.9722, found 315.9717.

[0156] Example 3

[0157] The specific compound prepared in Example 3 is

[0158] The substrate was alcohol, and 53.0 mg of colorless oily liquid was obtained with a yield of 30%. 1 H NMR (400MHz, CDCl3) δ8.01(d,J=8.3Hz,1H),7.88(d,J=8.5Hz,1H),7.79(d,J=7.9Hz,1 H),7.60–7.47(m,2H),7.46–7.37(m,2H),4.34(t,J=7.5Hz,2H),3.51(t,J=7.5Hz,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.0Hz, 2F), -89.0 (t, J = 5.0Hz, 2F). 13C NMR (101MHz, CDCl3) δ134.1,132.5,132.0,129.1,128.0,127.4,126.5,125.9,125.7,123.3,117.0(t t,J=271.5,31.7Hz),114.0(tt,J=312.4,46.0Hz),65.7(t,J=4.9Hz),32.7.MS(DART,m / z):351.0(M+H + ).HRMS(DART):m / z Calcd.for C 14 H 12 OBrF4 + (M+H + )351.0002, found 350.9998.

[0159] Example 4

[0160] The specific compound prepared in Example 4 is

[0161] The substrate was alcohol, and 113.1 mg of colorless oily liquid was obtained with a yield of 57%. 1 H NMR (400MHz, CDCl3): δ7.42(d,J=8.3Hz,2H), 7.07(d,J=8.3Hz,2H), 4.01(t,J=6.2Hz,2H), 2.70(t,J=7.5Hz,2H), 2.08–1.92(m,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.0 Hz, 2F), -89.2 (t, J = 5.0 Hz, 2F). 13 CNMR(101MHz,CDCl3)δ139.7,131.7,130.4,120.1,117.0(tt,J=270.7,31.4Hz), 114.0(tt,J=312.3,45.9Hz),64.6(t,J=5.0Hz),31.1,30.4.MS(EI,m / z,%):392(M + ,12.04),394(M + +2,24.21),396(M + +4,11.45),91(100),171(97.01),169(95.76),117(36.63).HRMS(EI):m / z Calcd.for C 11 H 10 OBr2F4(M)391.9035,found 391.9036.

[0162] Example 5

[0163] The specific compound prepared in Example 5 is

[0164] The substrate was alcohol, and 118.5 mg of colorless oily liquid was obtained with a yield of 72%. 1 H NMR (400MHz, CDCl3) δ7.30(t,J=7.5Hz,2H),7.20(t,J=8.0Hz,3H),4.14–3.96(m,2H),2.76–2.57(m,2H),1.84–1.67(m,4H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.0 Hz, 2F), -89.2 (t, J = 5.0 Hz, 2F). 13 C NMR(101MHz,CDCl3)δ142.0,128.56,128.54,126.1,119.7(tt,J=270.8,31.4Hz),114 .1(tt,J=312.2,46.1Hz),65.8(t,J=5.0Hz),35.4,28.5,27.4.MS(DART,m / z):328.0(M + ).HRMS(DART):m / z Calcd.for C 12 H 13 OBrF4(M)328.0080, found 328.0077.

[0165] Example 6

[0166] The specific compound prepared in Example 6 is

[0167] The substrate was alcohol, and 102.9 mg of colorless oily liquid was obtained with a yield of 65%. 1 H NMR (400MHz, CDCl3) δ7.29(t,J=7.5Hz,2H),7.19(t,J=6.8Hz,3H),4.02(t,J=6.5Hz,2H),2.70–2.58(m,2H),1.81–1.61(m,4H),1.52–1.40(m,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.0 Hz, 2F), -89.2 (t, J = 5.0 Hz, 2F). 13C NMR (101MHz, CDCl3) δ142.4, 128.53, 128.47, 125.9, 117.0 (tt, J = 270.6, 31.5Hz), 114.1 (tt,J=312.4,46.2Hz),65.9(t,J=5.0Hz),35.9,31.0,28.9,25.3.MS(EI,m / z,%):342(M + ,14.91),344(M + +2,14.5),91(100),92(38.68).HRMS(EI):m / z Calcd.forC 13 H 15 OBrF4 342.0242(M), found 342.0247.

[0168] Example 7

[0169] The specific compound prepared in Example 7 is

[0170] The substrate was alcohol, and 132.6 mg of colorless oily liquid was obtained with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ7.10 (d, J = 8.6 Hz, 2H), 6.84 (d, J = 8.6 Hz, 2H), 4.08–3.98 (m, 2H), 3.09 (s, 3H), 2.67–2.55 (m, 2H), 1.81–1.64 (m, 4H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.1Hz, 2F), -89.2 (t, J = 5.1Hz, 2F).

[0171] Example 8

[0172] The specific compound prepared in Example 8 is

[0173] The substrate was alcohol, and 100.3 mg of white solid was obtained with a yield of 52%. 1 H NMR (400MHz, CDCl3) δ7.89–7.81(m,2H),7.77–7.68(m,2H),4.11(t,J=6.2Hz,2H),3.84(t,J=6.9Hz,2H),2.13(p,J=6.5Hz,2H). 19 F NMR (376MHz, CDCl3) δ-67.9 (t, J = 5.0 Hz, 2F), -89.6 (t, J = 5.0 Hz, 2F). 13C NMR(101MHz,CDCl3)δ168.3,134.2,132.2,123.4,116.8(tt,J=271.7,31.8Hz),11 3.7(tt,J=312.4,45.5Hz),63.7(t,J=5.3Hz),34.9,28.1.MS(ESI,m / z):384.0(M+H + ),406.0(M+Na + ).HRMS(ESI):m / z Calcd.for C 13 H 11 O3BrF4N + (M+H + )383.9853, found 383.9846.

[0174] Example 9

[0175] The specific compound prepared in Example 9 is

[0176] The substrate was alcohol, and 82.1 mg of colorless oily liquid was obtained with a yield of 41%. 1 H NMR (400MHz, CDCl3) δ7.65(d,J=7.6Hz,1H),7.56(s,1H),7.34(t,J=7.9Hz,1H),7.09(dd,J=8.2,1.4Hz,1H),4. 37(q,J=7.1Hz,2H), 4.26(t,J=6.1Hz,2H), 4.13(t,J=5.9Hz,2H), 2.20(p,J=5.9Hz,2H), 1.39(t,J=7.1Hz,3H). 19 F NMR (376MHz, CDCl3) δ-67.8 (t, J = 4.9 Hz, 2F), -89.4 (t, J = 4.9 Hz, 2F).

[0177] Example 10

[0178] The specific compound prepared in Example 10 is

[0179] The substrate was alcohol, and 69.2 mg of colorless oily liquid was obtained with a yield of 44%. 1 H NMR (400MHz, CDCl3) δ8.52(d,J=4.8Hz,2H),7.14(d,J=4.9Hz,2H),4.02(t,J=6.0Hz,2H),2.75(t,J=7.6Hz,2H),2.10–1.96(m,2H). 19F NMR(376MHz, CDCl3)δ-67.8(t,J=4.9Hz,2F),-89.4(t,J=4.9Hz,2F).MS(ESI,m / z):316.0(M+H + ).HRMS(ESI):m / z Calcd.for C 13 H 11 O3F3N + (M+H + )315.9955, found315.9958.

[0180] Embodiment 11

[0181] The specific compound prepared in Example 11 is

[0182] The substrate was alcohol, and 119.6 mg of colorless oily liquid was obtained with a yield of 73%. 1 H NMR(400MHz, CDCl3)δ7.30(t,J=7.4Hz,1H),7.21(t,J=7.3Hz,2H),4.60–4.46(m,1 H),2.73(dtd,J=23.4,14.2,6.1Hz,1H),2.09–1.79(m,1H),1.39(d,J=6.2Hz,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.1Hz, 2F), -85.7–-86.7 (m, 2F).

[0183] Example 12

[0184] The specific compound prepared in Example 12 is

[0185] The substrate was alcohol, and 152.3 mg of colorless oily liquid was obtained with a yield of 88%. 1 H NMR (400MHz, CDCl3) δ6.96–6.83(m,4H),4.46(m,1H),4.37–4.25(m,2H),4.17(ddd,J=17.8,11.0,6.3Hz,2H). 19 F NMR (376MHz, CDCl3) δ-67.9 (t, J=4.8Hz, 2F), -89.6 (dt, J=9.6, 4.9Hz, 2F). 13C NMR (101MHz, CDCl3) δ143.0,142.6,122.1,122.0,117.6,117.5,116.8(tt,J= 273.0, 32.0Hz), 113.5 (tt, J = 311.9, 44.9Hz), 70.4, 64.6, 63.4 (t, J = 4.9Hz).

[0186] Embodiment 13

[0187] The specific compound prepared in Example 13 is

[0188] The substrate was alcohol, and 159.2 mg of colorless oily liquid was obtained with a yield of 76%. 1 H NMR (400MHz, CDCl3) δ7.36 (q, J = 8.4Hz, 4H), 4.70 (tt, J = 6.8, 3.6Hz, 1H), 3.98–3.20 (m, 4H), 2.18–1.60 (m, 4H). 19 F NMR (376MHz, CDCl3) δ-68.0 (t, J = 5.1Hz, 2F), -87.1 (t, J = 5.1Hz, 2F). 13 C NMR (101MHz, CDCl3) δ169.5,136.1,134.0,128.9,128.5,117.0 (tt,J=272.2,31.6Hz) ,113.9(tt,J=312.7,46.1Hz),72.6(t,J=3.9Hz),44.1,31.8.MS(ESI,m / z):418.0(M+H + ).HRMS(ESI):m / zCalcd.for C 14 H 14 O2NBrClF4 + (M+H + )417.9827, found 417.9829.

[0189] Embodiment 14

[0190] The specific compound prepared in Example 14 is

[0191] The substrate was alcohol, and 170.8 mg of white solid was obtained with a yield of 81%. 1H NMR (400MHz, CDCl3) δ7.76(d,J=8.2Hz,2H),7.61(t,J=7.2Hz,1H),7.54(t,J=7.5Hz,2H),4.54–4.45(m,1H),3.23–3.03(m,4H),2.09–1.81(m,4H). 19 F NMR (376MHz, CDCl3) δ-68.1 (t, J = 5.0Hz, 2F), -87.3 (t, J = 4.9Hz, 2F). 13 C NMR (101MHz, CDCl3) δ136.2, 133.1, 129.2, 127.7, 116.9 (tt, J = 271.4, 31.7Hz), 11 3.8(tt,J=312.8,45.9Hz),71.7(t,J=4.0Hz),42.6,31.1.MS(ESI,m / z):420.0(M+H + ).HRMS(ESI):m / z Calcd.for C 13 H 15 O3NBrF4S + (M+H + )419.9887,found419.9889.

[0192] Embodiment 15

[0193] The specific compound prepared in Example 15 is

[0194] The substrate was alcohol, and 166.8 mg of bright yellow oily liquid was obtained with a yield of 81%. 1 H NMR (400MHz, CDCl3) δ7.72(d,J=8.1Hz,2H),7.50(d,J=8.1Hz,2H),4.77–4.68(m,1H),3.86(s,2H),3.55(s,1H),3.34(s,1H),2.13–1.62(m,4H). 19 F NMR (376MHz, CDCl3) δ-68.0 (t, J = 5.0Hz, 2F), -87.2 (t, J = 5.1Hz, 2F). 13 C NMR (101MHz, CDCl3) δ168.5,140.1,132.7,127.7,118.1,117.1(tt,J=271.9,31.6Hz),11 3.9,113.8(tt,J=312.6,45.7Hz),72.3(t,J=4.0Hz),43.9,31.3.HRMS(EI):m / zCalcd.for C15 H 13 O2N2BrF4(M)408.0097, found 408.0095.

[0195] Example 16

[0196] The specific compound prepared in Example 16 is

[0197] The substrate was alcohol, and 109.7 mg of colorless oily liquid was obtained with a yield of 66%. 1 H NMR (400MHz, CDCl3)δ 1 H NMR (400MHz, cdcl3) δ2.21 (s, 3H), 2.08 (d, J = 2.3Hz, 6H), 1.66 (t, J = 2.9Hz, 6H). 19 F NMR (376MHz, CDCl3) δ-67.9 (t, J = 4.9Hz, 2F), -78.9 (t, J = 4.8Hz, 2F). 13 C NMR (101MHz, CDCl3) δ117.8 (tt, J = 274.1, 31.0Hz), 114.8 (tt, J = 313.4, 48.0Hz), 85.3, 43.1, 35.9, 31.3. HRMS (EI): m / z Calcd.for C 12 H 15 OBrF4(M)330.0242,found330.0241.

[0198] Embodiment 17

[0199] The specific compound prepared in Example 17 is

[0200] The substrate was alcohol, and 138.7 mg of white solid was obtained with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ7.74(d,J=4.6Hz,1H),7.68(d,J=3.4Hz,1H),7.26–7.22(m,1 H),4.95–4.86(m,1H),4.21(dd,J=10.3,6.7Hz,2H),3.91(dd,J=10.2,4.9Hz,2H). 19 F NMR (376MHz, CDCl3) δ-68.5 (t, J = 4.8Hz, 2F), -88.6 (t, J = 4.7Hz, 2F). 13C NMR (101MHz, CDCl3) δ134.3, 133.6, 128.1, 116.4 (tt, J = 274.3, 32.3Hz), 113.0 (tt, J = 312.1, 44.4Hz), 63.1 (t, J = 5.5Hz), 57.9. HRMS (EI): m / z Calcd.for C9H8O3NBrF4S2(M)396.9065,found 396.9065.

[0201] Embodiment 18

[0202] The specific compound prepared in Example 18 is

[0203] The substrate was alcohol, and 132.7 mg of colorless oily liquid was obtained with a yield of 59%. 1 H NMR (400MHz, CDCl3) δ7.45(d,J=7.4Hz,2H),7.37(t,J=7.4Hz,2H),7.30(t,J=7.2Hz,1H),6.82(d,J=8.1Hz,1H),6.74(d,J=1.8 Hz,1H),6.67(dd,J=8.1,1.8Hz,1H),5.14(s,2H),4.02(t,J=6.2Hz,2H),3.89(s,3H),2.69(t,J=7.4Hz,2H),2.05–1.96(m,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.1Hz, 2F), -89.1 (t, J = 5.1Hz, 2F). 13 C NMR (101MHz, CDCl3) δ149.8,146.8,137.5,133.9,128.6,127.9,127.4,120.5,117.0(tt,J=270.9,31.6H z),114.5,114.0(tt,J=312.4,46.3Hz),112.6,71.4,64.8(t,J=5.0Hz),56.1,31.2,30.6.HRMS(EI):m / z Calcd.forC 19 H 19 O3BrF4(M)450.0454,found 450.0451.

[0204] Embodiment 19

[0205] The specific compound prepared in Example 19 is

[0206] The substrate was alcohol, and 165.1 mg of colorless oily liquid was obtained with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ7.79(d,J=8.8Hz,2H),7.71(d,J=8.5Hz,2H),7.45(d,J=8.5Hz,2H), 6.97(d,J=8.8Hz,2H), 4.27(t,J=6.0Hz,2H), 4.17(t,J=5.9Hz,2H), 2.23(p,J=6.0Hz,2H). 19 F NMR (376MHz, CDCl3) δ-67.8 (t, J = 5.0 Hz, 2F), -89.4 (t, J = 5.0 Hz, 2F).

[0207] Embodiment 20

[0208] The specific compound prepared in Example 20 is

[0209] The substrate was alcohol, and 141.2 mg of colorless oily liquid was obtained with a yield of 63%. 1 H NMR(400MHz, CDCl3)δ7.70(d,J=8.1Hz,1H),7.37–7.23(m,4H),7.19(t,J=7.6 Hz,3H),7.10–7.04(m,1H),5.40(s,2H),4.69–4.62(m,2H),4.48–4.41(m,2H). 19 FNMR(376MHz, CDCl3)δ-67.7(t,J=4.9Hz,2F),-88.9(t,J=4.9Hz,2F). 13 CNMR(101MHz, CDCl3)δ155.4,141.8,137.5,128.8,127.7,127.1,120.2,119.5,117.0(tt,J=271.7,31.8 Hz),113.8(tt,J=312.2,45.6Hz),113.0,109.0,66.3,64.1(t,J=5.0Hz),52.5.MS(ESI,m / z):447.0(M+H + ).HRMS(ESI):m / z Calcd.forC 18 H 16 O2N2BrF4 + (M+H + )447.0326, found 447.0328.

[0210] Embodiment 21

[0211] The specific compound prepared in Example 21 is

[0212] The substrate was alcohol, and 132.2 mg of colorless oily liquid was obtained with a yield of 80%. 1 H NMR (400MHz, CDCl3) δ7.36–7.27(m,2H),7.04–6.96(m,1H),6.96–6.85(m,2H),4.91–4.77 (m,1H),4.09(ddd,J=8.5,5.9,2.5Hz,1H),4.03–3.94(m,1H),1.49(dd,J=6.3,3.2Hz,3H). 19 F NMR (376MHz, CDCl3) δ-67.8 (t, J = 4.8Hz, 2F), -86.2–-87.2 (m, 2F). 13 C NMR (101MHz, CDCl3) δ158.5,129.7,121.5,117.1(t,J=272.0,31.6Hz),114.9,114.0(tt,J=312.5,46.0Hz),72.7(t,J=3.8Hz),70.3,18.2.HRMS(EI):m / z Calcd.for C 10 H9O2BrF4(M)329.9879, found 329.9869.

[0213] Embodiment 22

[0214] The specific compound prepared in Example 22 is

[0215] The substrate was alcohol, and 134.8 mg of yellow oily liquid was obtained with a yield of 64%. 1 H NMR (400MHz, CDCl3) δ6.15 (s, 2H), 4.24 (t, J = 6.1Hz, 2H), 4.04 (t, J = 5.9Hz, 2H), 3.83 (s, 6H), 3.78 (s, 3H), 2.17 (p, J = 5.9Hz, 2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 4.8Hz, 2F), -89.3 (t, J = 4.9Hz, 2F).

[0216] Embodiment 23

[0217] The specific compound prepared in Example 23 is

[0218] The substrate was alcohol, and 219.7 mg of yellow solid was obtained with a yield of 88%.1 H NMR (400MHz, CDCl3) δ8.55(d,J=8.5Hz,1H),8.44(d,J=8.6Hz,1H),8.21(d,J=7.3Hz,1H),7.53(dt,J=8.6,8.1Hz,2H),7.18(d,J=7.5Hz,1H),4.9 5(s,1H),3.70(dd,J=11.7,4.9Hz,1H),3.66–3.58(m,1H),3.55(d,J=11 .7Hz,1H),3.47(dd,J=17.0,8.7Hz,1H),2.87(s,6H),2.21–2.07(m,2H). 19 F NMR (376MHz, CDCl3) δ-68.4 (t, J = 5.0 Hz, 2F), -87.6 (t, J = 5.0 Hz, 2F). 13 C NMR (101MHz, CDCl3) δ151.8,133.7,130.8,130.6,130.2,129.8,128.3,123.3,119.6,116.7(tt,J= 272.9,31.8Hz),115.4,113.4(tt,J=312.5,44.8Hz),75.8(t,J=4.5Hz),53.2,45.53,45.49,32.6.

[0219] Embodiment 24

[0220] The specific compound prepared in Example 24 is

[0221] The substrate was alcohol, and 146.4 mg of white solid was obtained with a yield of 66%. 1 H NMR (400MHz, CDCl3) δ7.75(d,J=8.4Hz,2H),7.49(d,J=8.4Hz,2H),4.91(d,J=2.5Hz,1H),3.60(dd,J= 12.3, 4.6Hz, 1H), 3.56–3.48 (m, 1H), 3.41 (d, J=12.3Hz, 1H), 3.25 (q, J=8.8Hz, 1H), 2.17–2.04 (m, 2H). 19 FNMR (376MHz, CDCl3) δ-68.5 (t, J=4.9Hz, 2F), -87.1–-88.0 (m, 2F). 13C NMR (101MHz, CDCl3) δ139.7, 135.0, 129.6, 129.0, 116.6 (tt, J = 273.3, 32.1Hz), 113.3 (tt,J=312.4,44.9Hz),75.6(t,J=4.5Hz),53.8,45.9,32.4.MS(ESI,m / z):461.9(M+Na + ).HRMS(ESI):m / zCalcd.for C 12 H 11 O3NBrClF4NaS + (M+Na + )461.9160, found 461.9166.

[0222] Embodiment 25

[0223] The specific compound prepared in Example 25 is

[0224] The substrate was alcohol, and 116.1 mg of colorless oily liquid was obtained with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ7.16 (dd, J=8.4, 5.5Hz, 2H), 6.99 (t, J=8.7Hz, 2H), 4.66 (h, J=6.3H z,1H),2.94(dd,J=14.0,6.7Hz,1H),2.85(dd,J=14.0,5.9Hz,1H),1.34(d,J=6.3Hz,3H). 19 F NMR (376MHz, CDCl3) δ-67.8 (t, J=5.1Hz, 2F), -86.7 (qt, J=138.9, 5.0Hz, 2F), -116.2–-116.3 (m, 1F). 13 C NMR (101MHz, CDCl3) δ162.1 (d, J = 244.6Hz), 132.4 (d, J = 3.4Hz), 131.3 (d, J = 8.0Hz), 117.0 (tt, J = 2 71.3,31.4Hz),115.4(d,J=21.1Hz),114.1(tt,J=312.2,46.3Hz),75.7,42.4,20.8.HRMS(EI):m / z Calcd.for C 11 H 10 OBrF5(M)331.9835, found 331.9833.

[0225] Embodiment 26

[0226] The specific compound prepared in Example 26 is

[0227] The substrate was alcohol, and 59.3 mg of colorless oily liquid was obtained with a yield of 32%. 1 H NMR (400MHz, CDCl3) δ7.40 (s, 1H), 7.24–7.16 (m, 2H), 4.23 (t, J = 6.7Hz, 2H), 3.13 (t, J = 6.7Hz, 2H). 19 F NMR (376MHz, CDCl3) δ-67.8 (t, J = 5.0 Hz, 2F), -89.3 (t, J = 5.0 Hz, 2F). 13 C NMR (100MHz, CDCl3) δ134.9,133.8,133.1,132.4,129.6,127.4,116.9(tt,J=271.9, 31.6Hz), 113.8(tt,J=312.3,45.7Hz), 64.3(t,J=5.0Hz), 32.9.MS(EI,m / z,%): 368(M + ,7.41),370(M + +2,10.78),159(100),161(67.49),163(11.7).HRMS(EI):m / z Calcd.for C 10 H7OBrCl2F4(M)367.8993, found 367.8987.

[0228] Embodiment 27

[0229] The specific compound prepared in Example 27 is

[0230] The substrate was alcohol, and 51.4 mg of colorless oily liquid was obtained with a yield of 30%. 1 H NMR (400MHz, CDCl3) δ7.56(d,J=7.4Hz,1H),7.53(s,1H),7.49(d,J=8.0Hz,1H),7.36–7.22(m,2H),4.30(t,J=6.8Hz,2H),3.12(t,J=6.8Hz,2H). 19 F NMR (376MHz, CDCl3) δ-67.8 (t, J = 5.0Hz, 2F), -89.2 (t, J = 5.0Hz, 2F). 13C NMR (100MHz, CDCl3) δ155.4,142.4,127.8,124.7,122.7,119.4,117.0(tt,J=271.6,31.7H z),115.6,113.9(tt,J=312.3,45.7Hz),111.8,64.8(t,J=5Hz),23.8.MS(EI,m / z,%):340(M + ,13.25),342(M + +2,12.28),131(100),77(14.37),115(12.04).HRMS(EI):m / z Calcd.for C 12 H9O2BrF4(M)339.9722, found 339.9727.

[0231] Embodiment 28

[0232] The specific compound prepared in Example 28 is

[0233] The substrate was alcohol, and 132.1 mg of light yellow oily liquid was obtained with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ7.59 (d, J = 8.9 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 4.25 (t, J = 6.0 Hz, 2H), 4.13 (t, J = 6.0 Hz, 2H), 2.22 (p, J = 6.0 Hz, 2H). 19 F NMR (376MHz, CDCl3) δ-67.8 (t, J = 4.9 Hz, 2F), -89.4 (t, J = 4.9 Hz, 2F). 13 C NMR (100MHz, CDCl3) δ162.0, 134.1, 119.2, 116.9 (tt, J = 271.6, 31.7Hz), 113.8 (tt, J=312.3,45.7Hz),104.4,63.9,62.2(t,J=5.2Hz),28.8.MS(DART,m / z):356.0(M+H + ).HRMS(DART):m / z Calcd.for C 12 H 11 O2BrF4N + (M+H + )355.9904, found 355.9900.

[0234] Embodiment 29

[0235] The specific compound prepared in Example 29 is

[0236] The substrate was alcohol, and 113.9 mg of colorless oily liquid was obtained with a yield of 57%. 1 H NMR(400MHz, CDCl3) δ6.84(d,J=8.1Hz,1H),6.77–6.67(m,2H),5.96(ddt,J=16.8,10.1,6.7Hz,1H),5.15–5.01 (m,2H),4.27(t,J=6.1Hz,2H),4.11(t,J=6.1Hz,2H),3.85(s,3H),3.34(d,J=6.7Hz,2H),2.21(p,J=6.1Hz,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.0 Hz, 2F), -89.3 (t, J = 5.0 Hz, 2F). 13 C NMR (100MHz, CDCl3) δ149.9,146.6,137.7,133.8,120.7,116.9(tt,J=271.4,31.6Hz),115.8,114.6,11 4.0(tt,J=312.4,45.8Hz),112.7,65.4,62.8(t,J=5.3Hz),56.0,39.9,29.2.MS(DART,m / z):401.0(M+H + ).HRMS(DART):m / z Calcd.for C 15 H 18 O3BrF4 + (M+H + )401.0370, found 401.0366.

[0237] Embodiment 30

[0238] The specific compound prepared in Example 30 is

[0239] The substrate was alcohol, and 88.2 mg of colorless oily liquid was obtained with a yield of 44%. 1 H NMR (400MHz, CDCl3) δ7.10(d,J=8.6Hz,2H),6.82(d,J=8.5Hz,2H),4.24(t,J=6.2Hz,2H),4.0 5(t,J=6.0Hz,2H),2.89–2.79(m,2H),2.78–2.68(m,2H),2.17(p,J=6.1Hz,2H),2.13(s,3H). 19F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.0 Hz, 2F), -89.3 (t, J = 5.0 Hz, 2F). 13 C NMR (100MHz, CDCl3) δ208.1, 157.1, 133.5, 129.4, 116.9 (tt, J = 271.4, 31.6Hz), 114.6, 113.9 (tt,J=312.4,45.9Hz),63.6,62.6(t,J=5.3Hz),45.4,30.1,29.0,28.9.MS(EI,m / z,%):400(M + ,3.61),402(M + +2,3.51),61(100),45(94.31),70(92.71),73(45.34),88(42.06).HRMS(EI):m / z Calcd.forC 15 H 17 O3BrF4(M)400.0297, found 400.0293.

[0240] Embodiment 31

[0241] The specific compound prepared in Example 31 is

[0242] The substrate was alcohol, and 85.8 mg of white solid was obtained with a yield of 40%. 1 H NMR (400MHz, CDCl3) δ7.16(d,J=8.6Hz,2H),6.86(d,J=8.7Hz,2H),4.24(t,J=6.1Hz,2H),4.06(t,J =5.9Hz,2H),2.99(tt,J=12.1,3.3Hz,1H),2.57–2.42(m,4H),2.28–2.10(m,4H),1.99–1.82(m,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.0 Hz, 2F), -89.3 (t, J = 5.0 Hz, 2F). 13 C NMR (100MHz, CDCl3) δ211.3,157.4,137.4,127.7,116.9(tt,J=271.4,31.6Hz),114.7,113.9(t t,J=312.4,45.8Hz),63.6,62.7(t,J=5.2Hz),42.0,41.5,34.3,29.1.MS(DART,m / z):427.1(M+H +).HRMS(DART):m / z Calcd.for C 17 H 20 O3BrF4 + (M+H + )427.0527, found 427.0523.

[0243] Embodiment 32

[0244] The specific compound prepared in Example 32 is

[0245] The substrate was alcohol, and 91.2 mg of colorless liquid was obtained with a yield of 45%. 1 H NMR(400MHz, CDCl3)δ8.00(d,J=8.9Hz,2H),6.91(d,J=8.9Hz,2H),4.35(q,J=7.1Hz,2H), 4.25(t,J=6.1Hz,2H), 4.13(t,J=6.0Hz,2H), 2.21(p,J=6.0Hz,2H), 1.38(t,J=7.1Hz,3H). 19 F NMR (376MHz, CDCl3) δ-67.8 (t, J = 5.0 Hz, 2F), -89.4 (t, J = 5.0 Hz, 2F). 13 C NMR (100MHz, CDCl3) δ166.4,162.4,131.7,123.4,116.9 (tt,J=271.6,31.5Hz),114.1,113 .9(tt,J=312.3,45.9Hz),63.7,62.4(t,J=5.3Hz),60.8,28.9,14.4.MS(EI,m / z,%):402(M + ,12.36),404(M + +2,12.33),84(100),121(86.26),86(64.09),138(36.98).HRMS(EI):m / z Calcd.for C 14 H 15 O4BrF4(M)402.0090, found 402.0092.

[0246] Embodiment 33

[0247] The specific compound prepared in Example 33 is

[0248] The substrate is alcohol, and the fluorine spectrum yield is 54%. (Trifluorotoluene is used as internal standard, δ-63.0ppm). 19F NMR(376MHz,DMF)δ-70.4(m,2F),-88.7(m,2F).

[0249] Embodiment 34

[0250] The specific compound prepared in Example 34 is

[0251] The substrate is alcohol, and the fluorine spectrum yield is 59%. (Trifluorotoluene is used as internal standard, δ-63.0ppm). 19 F NMR(376MHz,DMF)δ-70.3(m,2F),-89.4(m,2F).

[0252] Embodiment 35

[0253] The specific compound prepared in Example 35 is

[0254] The substrate is alcohol, and the fluorine spectrum yield is 91%. (Trifluorotoluene is used as internal standard, δ-63.0ppm). 19 F NMR(376MHz,DMF)δ-70.3(m,2F),-81.4(m,2F).

[0255] Embodiment 36

[0256] The specific compound prepared in Example 36 is

[0257] The substrate is alcohol, and the fluorine spectrum yield is 82%. (Trifluorotoluene is used as internal standard, δ-63.0ppm). 19 F NMR(376MHz,DMF)δ-70.1(m,2F),-80.7(m,2F).

[0258] Embodiment 37

[0259] The specific compound prepared in Example 37 is

[0260] The substrate is alcohol, and the fluorine spectrum yield is 84%. (Trifluorotoluene is used as internal standard, δ-63.0ppm). 19 F NMR(376MHz,DMF)δ-68.0(m,2F),-87.2(m,2F).

[0261] Embodiment 38

[0262] The specific compound prepared in Example 38 is

[0263] The substrate was alcohol, and 203.4 mg of colorless liquid was obtained with a yield of 61%. 1H NMR (400MHz, CDCl3) δ4.34(t,J=6.1Hz,2H),3.76(t,J=5.8Hz,2H),2.58(t,J=6.7Hz,2H),2.23 –2.04(m,11H),1.88–1.70(m,2H),1.63–1.18(m,18H),1.18–1.00(m,6H),0.90–0.80(m,12H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 4.9 Hz, 2F), -89.3 (t, J = 4.9 Hz, 2F). 13 C NMR (100MHz, CDCl3) δ148.1,148.0,127.9,125.9,123.1,117.7,117.1(tt,J=2 71.4,31.6),114.0(tt,J=312.2,45.8Hz),75.0,67.9,62.8(t,J=5.2Hz),40.2 ,39.6,37.8–37.4(4C),33.0,32.9,31.4,30.0,28.2,25.0,24.6,24.0,22.9,2 2.8,21.2,20.8,19.9–19.7(2C),12.7,11.93,11.86.MS(DART,m / z):667.3(M+H + ).HRMS(DART):m / z Calcd.for C 34 H 56 O3BrF4 + (M+H + )667.3343, found667.3334.

[0264] Embodiment 39

[0265] The specific compound prepared in Example 39 is

[0266] The substrate was alcohol, and 66.0 mg of white solid was obtained with a yield of 33%. 1 H NMR(400MHz, CDCl3)δ7.67(d,J=9.5Hz,1H),7.39(d,J=8.5,1H),6.91–6.77(m,2H),6.2 9(d,J=9.5Hz,1H), 4.26(t,J=6.0Hz,2H), 4.14(t,J=5.9Hz,2H), 2.24(p,J=5.9Hz,2H). 19F NMR (376MHz, CDCl3) δ-67.8 (t, J = 4.9 Hz, 2F), -89.5 (t, J = 5.0 Hz, 2F). 13 C NMR (100MHz, CDCl3) δ162.0, 161.9, 155.8, 143.9, 129.0, 116.8 (tt, J=271.7, 31.8Hz), 113.8 (tt, J= 312.4, 45.6Hz), 113.13, 113.05, 112.9, 101.5, 64.2, 62.3 (t, J = 5.2Hz), 28.7.MS (EI, m / z, %): 398 (M + ,3.69),400(M + +2,3.07),131(100),51(30.85),134(30.24),95(26.85).HRMS(EI):m / z Calcd.forC 14 H 11 O4BrF4(M)397.9777, found 397.9784.

[0267] Embodiment 40

[0268] The specific compound prepared in Example 40 is

[0269] Under nitrogen protection, potassium tert-butoxide (22.4 mg, 0.2 mmol, 1.0 equiv) and zinc powder (1.3 mg, 0.02 mmol, 0.1 equiv) were weighed into a 25 mL sealed tube, anhydrous DMF (2 mL) was added, and the mixture was stirred at room temperature for 5 minutes. 1,2-dibromotetrafluoroethane (156 mg, 0.6 mmol, 3.0 equiv) was added, and the mixture was stirred at -5 to 0°C for 6 hours. After returning to room temperature, the reaction was continued at room temperature for 12 hours. Trifluorobenzene was used as an internal standard (δ-63.0 ppm) for fluorine spectrum analysis. The fluorine spectrum yield of the target product was 62%. 19 F NMR(376MHz,DMF)δ–70.4(m,2F),-81.6(m,2F).

[0270] Embodiment 41

[0271] The specific compound prepared in Example 41 is

[0272] Under nitrogen protection, weigh (5mmol, 1.0equiv) and zinc powder (33mg, 0.5mmol, 0.1equiv) were placed in a 250-mL sealed tube, anhydrous DMF (50mL) was added, and then NaH (252mg, 95% purity, 10.0mmol, 2.0equiv) was slowly added. After stirring at room temperature for 6 hours, 1,2-dibromotetrafluoroethane (3.897g, 15.0mmol, 3.0equiv) was added. After stirring for 5-10 minutes, the mixture was stirred at -5-0℃ for 6 hours. After returning to room temperature, the reaction was continued at room temperature for 12 hours, and ethyl acetate was added for dilution. Saturated aqueous ammonium chloride was added for quenching. Water was added and the mixture was extracted with ethyl acetate three times. The organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated, mixed with silica gel, and separated by rapid column chromatography with petroleum ether as the eluent to obtain 1.30g of colorless oily liquid with a yield of 82%.

[0273] Embodiment 42

[0274] The specific compound prepared in Example 42 is

[0275] Under nitrogen protection, weigh (5mmol, 1.0equiv) and zinc powder (33mg, 0.5mmol, 0.1equiv) were placed in a 250-mL sealed tube, anhydrous DMF (50mL) was added, and then NaH (252mg, 95% purity, 10.0mmol, 2.0equiv) was slowly added. After stirring at room temperature for 6 hours, 1,2-dibromotetrafluoroethane (3.897g, 15.0mmol, 3.0equiv) was added. After stirring for 5-10 minutes, the mixture was stirred at -5-0℃ for 6 hours. After returning to room temperature, the reaction was continued at room temperature for 12 hours, and ethyl acetate was added for dilution. Saturated aqueous ammonium chloride was added for quenching, water was added, and ethyl acetate was extracted three times. The organic phases were combined, washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated, mixed with silica gel, and separated by rapid column chromatography with petroleum ether as the eluent to obtain 1.13g of colorless oily liquid with a yield of 68%.

[0276] Examples 43-53

[0277] Investigation of material ratio and solvent

[0278]

[0279] Under nitrogen protection, weigh (0.2mmol, 1.0equiv) and zinc powder (x mmol) were placed in a 25-mL sealed tube. After adding dry solvent (2mL), NaH (10.8mg, 95% purity, 0.4mmol, 2.0equiv) was slowly added. After stirring at room temperature for 4 hours, 1,2-dibromotetrafluoroethane (ymmol) was added. The temperature was raised to 60°C and the reaction was continued for t hours. Trifluorotoluene was used as the internal standard and the fluorescence spectrum was used for detection. The yield.

[0280] Using phenylbutanol (1) as a template substrate, 2 equivalents of sodium hydride as a base, and zinc powder as an initiator, its reaction with BrCF2CF2Br in DMF solvent was investigated (Table 1). First, 0.2 equivalents of zinc powder were added as an initiator, and the reaction was heated at 60°C for 9 hours to obtain bromotetrafluoroethylphenylbutyl ether 2 with a 25% fluorine spectrum yield.

[0281] Since extending the reaction time to 16 hours did not significantly improve the reaction yield, the equivalent of BrCF2CF2Br was optimized. The amount of BrCF2CF2Br was increased from the initial 2.5 equivalents to 3 equivalents, 3.5 equivalents, and 4 equivalents, and it was found that when the amount of BrCF2CF2Br added was 3 equivalents, it was better and the yield could be increased to 58%.

[0282] Then we tried to reduce the equivalent of zinc powder to 0.1 equivalent, and found that the yield did not drop too much, and a yield of 54% could be obtained when the reaction time was 12 hours. When zinc powder was not added, the reaction could also occur, but the yield dropped to 27%.

[0283] Then the solvent DMF was replaced with DMSO, and it was found that the yield decreased significantly.

[0284] Table 1 Investigation of material ratio and solvent

[0285]

[0286]

[0287] Examples 54-61

[0288] Study on reaction temperature

[0289]

[0290] Under nitrogen protection, weigh (0.2mmol, 1.0equiv) and zinc powder (0.02mmol, 0.1equiv) were placed in a 25-mL sealed tube, and dry DMF (2mL) was added. Then, NaH (10.8mg, 95% purity, 0.4mmol, 2.0equiv) was slowly added. After stirring at room temperature for 4 hours, 1,2-dibromotetrafluoroethane (0.6mmol) was added. The reaction was carried out at different temperatures T for t hours. Trifluorotoluene was used as the internal standard and the fluorescence spectrum was used for detection. The yield.

[0291] When the reaction temperature was raised to 80°C, the reaction yield dropped to 40%. Attempting to lower the temperature yielded better results, with the yield increasing to 67% at 50°C. Further lowering the temperature to 40°C increased the reaction yield to 71%, and reacting at room temperature for 16 hours also yielded 69%, which shows that lowering the reaction temperature is beneficial to improving the reaction yield.

[0292] Then we tried to react at a lower temperature. We first placed the reaction system at -5 to 0°C for 6 hours, and then returned it to room temperature for 12 hours. We could get a yield of 83%. We placed the reaction system at -10°C and -40°C for 6 hours, and the yields decreased to 75%. Finally, we screened the reaction time at -5 to 0°C and found that extending the reaction time did not increase the yield.

[0293] Thus, the optimal conditions for the reaction of alcohol with BrCF2CF2Br to generate 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether were obtained. In addition, it can be seen from the process of condition optimization that low temperature is more conducive to the reaction, but it cannot inhibit the formation of protonated byproduct tetrafluoroethyl alkyl ether.

[0294] Table 2 Investigation of reaction temperature

[0295] Example No. Reaction temperature T and reaction time t Fluorine spectrum yield Embodiment 54 80℃, 12 hours 40％ Embodiment 55 60℃, 12 hours 54％ Embodiment 56 50℃, 12 hours 67％ Embodiment 57 40℃, 12 hours 71％ Embodiment 58 Room temperature, 16 hours 69％ Embodiment 59 -5℃, 6 hours; then room temperature, 12 hours 83％ Embodiment 60 -10℃, 6 hours; then room temperature, 12 hours 75％ Embodiment 61 -40℃, 6 hours; then room temperature, 12 hours 75％

[0296] Examples 62-81 Typical Operations for Producing Trifluorovinyl Ether from 2-Bromo-1,1,2,2-Tetrafluoroethyl Ether

[0297] The debromination reaction of the above-prepared bromotetrafluoroethyl alkyl ether (ROCF2CF2Br) was carried out to investigate the universality of the substrate.

[0298]

[0299] In the glove box, zinc powder (29.4 mg, 0.45 mmol, 1.5 equiv) and ZnCl2 (12.3 mg, 0.09 mmol, 0.3 equiv) were weighed into a dried 25-mL sealed tube, and 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether (0.30 mmol, 1.0 equiv) and anhydrous CH3CN (6 mL) were added under N2 protection after removal from the glove box. The mixture was heated at 95°C for 12 hours. After the reaction was completed, the mixture was concentrated by rotary evaporation, mixed with silica gel, and separated by column chromatography using petroleum ether as the eluent to obtain the target product.

[0300]

[0301] a Reaction conditions: ROCF2CF2Br (0.3mmol, 1.0equiv), Zn (0.45mmol, 1.5equiv), ZnCl2 (0.09mmol, 0.3equiv), MeCN 6.0mL. Isolated yield. b EtOAc 0.5 mL was added as a co-solvent. PhOCF3 was used as an internal standard. 19 The yield was determined by FNMR.

[0302] 2-Bromo-1,1,2,2-tetrafluoroethyl ethers of various primary, secondary, and tertiary alcohols can be converted to trifluorovinyl ethers in moderate to excellent yields, with little hydrogenation byproduct (ROCF2CF2H) being observed. Due to the poor solubility of some substrates in acetonitrile, it is difficult for the raw materials to react completely. Adding ethyl acetate to aid solubilization can promote the reaction.

[0303] Embodiment 62

[0304] The specific compound prepared in Example 62 is

[0305] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 52.8 mg of colorless oily liquid is obtained with a yield of 81%. 1 H NMR (400MHz, CDCl3) δ7.31(dd,J=8.5,7.5Hz,2H),6.99(t,J=7.4Hz,1H),6.93(d,J=7.9Hz,2H),4.36–4.30(m,2H),4.26–4.19(m,2H). 19F NMR (376MHz, CDCl3) δ-122.6 (dd, J=103.2, 56.3Hz, 1F), -129.3 (dd, J=108.2, 103.3Hz, 1F), -134.9 (dd, J=108.3, 56.4Hz, 1F). 13 C NMR (101MHz, CDCl3) δ158.4, 146.0 (ddd, J=277.0, 270.5, 66.4Hz), 137.0 (ddd, J=261.5,47.3,40.6Hz),129.7,121.6,114.8,72.3,66.1.MS(EI,m / z,%):218(M + ,81.72),121(100),77(95.6),93(92.06),65(91.47),91(82.05),218(81.72).HRMS(EI):m / z Calcd.for C 10 H9O2F3(M)218.0555, found 218.0550.

[0306] Embodiment 63

[0307] The specific compound prepared in Example 63 is

[0308] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 59.3 mg of colorless oily liquid is obtained with a yield of 78%. 1 H NMR (400MHz, CDCl3) δ8.01(d,J=8.3Hz,1H),7.89(d,J=8.0Hz,1H),7.79(d,J=7.9Hz,1 H),7.61–7.48(m,2H),7.48–7.36(m,2H),4.32(t,J=7.6Hz,2H),3.52(t,J=7.6Hz,2H). 19 F NMR (376MHz, CDCl3) δ-122.9 (dd, J=104.7, 55.7Hz, 1F), -129.8 (dd, J=108.1, 104.7Hz, 1F), -134.3 (dd, J=108.0, 55.6Hz, 1F). 13C NMR (101MHz, CDCl3) δ146.1 (ddd, J=277.1, 269.4, 67.1Hz), 136.9 (ddd, J=260.8, 47.2, 40.0Hz), 134.1 ,132.5,132.0,129.1,127.9,127.3,126.5,125.9,125.7,123.2,74.0,32.7.MS(DART,m / z):351.0(M+H + ).MS(DART,m / z):253.1(M+H + ).HRMS(DART):m / z Calcd.for C 12 H 14 OF3 + (M+H + )253.0835, found 253.0835.

[0309] Embodiment 64

[0310] The specific compound prepared in Example 64 is

[0311] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 78.2 mg of colorless oily liquid is obtained with a yield of 89%. 1 H NMR (400MHz, CDCl3): δ7.42(d,J=8.3Hz,2H), 7.07(d,J=8.2Hz,2H), 3.98(t,J=6.0Hz,2H), 2.71(t,J=7.6Hz,2H), 2.05–1.92(m,2H). 19 F NMR (376MHz, CDCl3) δ-123.0 (dd, J=105.3, 55.7Hz, 1F), -130.3 (dd, J=107.8, 105.5Hz, 1F), -134.5 (dd, J=107.9, 55.7Hz, 1F). 13 C NMR (101MHz, CDCl3) δ146.1 (ddd, J=277.2, 269.0, 67.4Hz), 139.8, 136.8 (ddd, J=260.5, 47.1,39.7Hz),131.7,130.4,120.1,73.1(d,J=2.4Hz),31.1,30.6.MS(EI,m / z,%):294(M +,1.69),171(100),169(97.84),118(46.19),117(44.56),90(37.94).HRMS(EI):m / z Calcd.for C 11 H 10 OBrF3(M)293.9867, found 293.9874.

[0312] Embodiment 65

[0313] The specific compound prepared in Example 65 is

[0314] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 57.6 mg of colorless oily liquid is obtained with a yield of 83%. 1 H NMR (400MHz, CDCl3) δ7.30 (t, J = 7.4Hz, 2H), 7.23–7.15 (m, 3H), 4.05–3.93 (m, 2H), 2.73–2.55 (m, 2H), 1.82–1.66 (m, 4H). 19 F NMR (376MHz, CDCl3) δ-123.4 (dd, J=105.7, 55.4Hz, 1F), -130.6 (dd, J=107.7, 105.8Hz, 1F), -134.3 (dd, J=107.8, 55.4Hz, 1F). 13 C NMR (101MHz, CDCl3) δ146.1 (ddd, J=276.8, 268.8, 67.9Hz), 141.9, 136.9 (ddd, J=259.9, 46.9 ,39.6Hz),128.5(2C),126.1,74.3(d,J=2.2Hz),35.5,28.7,27.4.MS(DART,m / z):231.1(M+H + ).HRMS(DART):m / z Calcd.for C 12 H 14 OF3 + (M+H + )231.0991, found 231.0989.

[0315] Embodiment 66

[0316] The specific compound prepared in Example 66 is

[0317] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 60.4 mg of colorless oily liquid is obtained with a yield of 82%. 1 H NMR(400MHz, CDCl3)δ7.29(t,J=7.4Hz,2H),7.24–7.15(m,3H),3.99(td,J=6 .6,1.6Hz,2H),2.64(t,J=7.7Hz,2H),1.80–1.60(m,4H),1.51–1.39(m,2H). 19 FNMR (376MHz, CDCl3) δ-123.5(dd,J=105.8,55.4Hz,1F),-130.7(dd,J=107.5,106.2Hz,1F),-134.3(dd,J=107.8,55.4Hz,1F). 13 C NMR (101MHz, CDCl3) δ146.2 (ddd, J=276.5, 268.8, 67.7Hz), 142.4, 136.9 (ddd, J=259.9, 46.8, 39.6 Hz),128.51,128.46,125.9,74.4(d,J=2.5Hz),35.9,31.1,29.0,25.2.MS(DART,m / z):262.1(M+NH4 + ).HRMS(DART):m / zCalcd.for C 13 H 19 OF3N + (M+NH4 + )262.1413, found 262.1414.

[0318] Embodiment 67

[0319] The specific compound prepared in Example 67 is

[0320] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 59.1 mg of light yellow oily liquid is obtained with a yield of 76%. 1 H NMR (400MHz, CDCl3) δ7.09 (d, J = 8.5Hz, 2H), 6.84 (d, J = 8.5Hz, 2H), 4.04–3.94 (m, 2H), 3.79 (s, 3H), 2.60 (t, J = 7.0Hz, 2H), 1.79–1.63 (m, 4H). 19F NMR (376MHz, CDCl3) δ-123.4 (dd, J=105.7, 55.3Hz, 1F), -130.6 (dd, J=107.7, 105.9Hz, 1F), -134.3 (dd, J=107.8, 55.4Hz, 1F). 13 C NMR (101MHz, CDCl3) δ158.0, 146.1 (ddd, J=276.4, 268.8, 67.8Hz), 136.8 (ddd, J=260.1, 47.1,39.9Hz),134.0,129.4,113.9,74.3,55.3,34.5,28.6,27.6.MS(EI,m / z,%):260(M + ,1.46),121(100),163(15.79),122(10.98),91(10.8).HRMS(EI):m / z Calcd.for C 13 H 15 O2F3(M)260.1024,found 260.1029.

[0321] Embodiment 68

[0322] The specific compound prepared in Example 68 is

[0323] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 73.8 mg of colorless oily liquid is obtained with a yield of 86%. 1 H NMR (400MHz, CDCl3) δ7.90–7.80(m,2H),7.77–7.67(m,2H),4.06(td,J=6.2,1.2Hz,2H),3.84(t,J=6.9Hz,2H),2.11(p,J=6.5Hz,2H). 19 F NMR (376MHz, CDCl3) δ-122.9 (ddd, J=104.4, 55.9, 3.2Hz, 1F), -129.7 (dd, J=107.9, 104.6Hz, 1F), -135.1 (dd, J=108.0, 55.9Hz, 1F). 13 CNMR(101MHz, CDCl3)δ168.3,146.0(ddd,J=277.1,270.0,67.1Hz),136.6(ddd,J=260.8,47 .3,40.0Hz),134.1,132.1,123.4,71.8(d,J=2.0Hz),34.7,28.3.MS(DART,m / z):286.0(M+H+ ).HRMS(DART):m / z Calcd.for C 13 H 11 O3F3N + (M+H + )286.0686, found 286.0684.

[0324] Embodiment 69

[0325] The specific compound prepared in Example 69 is

[0326] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 68.2 mg of colorless oily liquid is obtained with a yield of 84%. 1 H NMR (400MHz, CDCl3) δ7.40 (s, 1H), 7.24–7.17 (m, 2H), 4.19 (td, J = 6.9, 1.5Hz, 2H), 3.13 (t, J = 6.9Hz, 2H). 19 F NMR (376MHz, CDCl3) δ-122.8 (dd, J=104.2, 56.0Hz, 1F), -129.7 (dd, J=108.2, 104.3Hz, 1F), -134.6 (dd, J=108.2, 56.1Hz, 1F). 13 CNMR (101MHz, CDCl3) δ146.0 (ddd, J=277.2, 269.8, 66.9Hz), 136.8 (ddd, J=261.0, 47.2, 40.2Hz), 134.9, 133.7, 133.2, 132.2, 129.6, 127.4, 72.6 (d, J = 2.7Hz), 33.1.

[0327] Embodiment 70

[0328] The specific compound prepared in Example 70 is

[0329] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 50.6 mg of colorless oily liquid is obtained with a yield of 70%. 1 H NMR (400MHz, CDCl3) δ7.55(d,J=7.5Hz,1H),7.53(s,1H),7.50(d,J=7.9Hz,1H),7.36–7.22(m,2H),4.28(td,J=6.9,1.5Hz,2H),3.11(t,J=6.7Hz,2H). 19F NMR (376MHz, CDCl3) δ-122.8 (dd, J=104.2, 56.0Hz, 1F), -129.7 (dd, J=108.2, 104.3Hz, 1F), -134.6 (dd, J=108.2, 56.1Hz, 1F). 13 C NMR (101MHz, CDCl3) δ155.4,146.1(ddd,J=277.4,269.6,66.7Hz),142.4,136.8(ddd,J=261.0,47.1 ,40.0Hz),127.8,124.6,122.7,119.4,115.6,111.8,73.0(d,J=2.5Hz),23.9.MS(EI,m / z,%):242(M + ,51.34),117(100),145(99.24),91(97.31),115(96.2),116(73.34).HRMS(EI):m / z Calcd.for C 12 H9O2F3(M)242.0555, found 242.0564.

[0330] Embodiment 71

[0331] The specific compound prepared in Example 71 is

[0332] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 81.5 mg of colorless oily liquid is obtained with a yield of 89%. 1 H NMR (400MHz, CDCl3) δ8.00(d,J=8.9Hz,2H),6.91(d,J=8.9Hz,2H),4.35(q,J=7.1Hz,2H),4.2 1(td,J=6.1,1.5Hz,2H),4.14(t,J=6.0Hz,2H),2.20(p,J=6.0Hz,2H),1.38(t,J=7.1Hz,3H). 19 F NMR (376MHz, CDCl3) δ-122.9 (dd, J=104.7, 56.0Hz, 1F), -130.1 (dd, J=108.1, 104.8Hz, 1F), -134.6 (dd, J=108.2, 56.0Hz, 1F). 13C NMR (101MHz, CDCl3) δ166.4,162.4,146.0(ddd,J=277.1,269.1,67.2Hz),136.8(ddd,J=260.9,47 .2,39.9Hz),131.7,123.3,114.1,70.9(d,J=2.5Hz),63.8,60.8,29.0,14.4.MS(EI,m / z,%):304(M + ,3.29),179(100),107(81.61),135(68.62),161(59.38),121(58.65).HRMS(EI):m / z Calcd.for C 14 H 15 O4F3(M)304.0922, found 304.0926.

[0333] Embodiment 72

[0334] The specific compound prepared in Example 72 is

[0335] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 87.2 mg of colorless oily liquid is obtained with a yield of 89%. 1 H NMR (400MHz, CDCl3) δ7.16(d,J=8.6Hz,2H),6.86(d,J=8.7Hz,2H),4.24(t,J=6.1Hz,2H),4.06(t,J =5.9Hz,2H),2.99(tt,J=12.1,3.3Hz,1H),2.57–2.42(m,4H),2.28–2.10(m,4H),1.99–1.82(m,2H). 19 F NMR (376MHz, CDCl3) δ-67.7 (t, J = 5.0 Hz, 2F), -89.3 (t, J = 5.0 Hz, 2F). 13 C NMR(101MHz, CDCl3)δ211.2,157.4,146.0(ddd,J=277.2,269.3,67.2Hz),137.3,136.8(ddd,J =260.6,47.2,40.0Hz),127.7,114.6,71.1,63.6,42.0,41.4,34.2,29.1.MS(EI,m / z,%):328(M + ,1.96),143(100),145(35.77),107(27.82).HRMS(EI):m / z Calcd.for C 17H 19 O3F3(M)328.1286,found328.1296.

[0336] Embodiment 73

[0337] The specific compound prepared in Example 73 is

[0338] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 81.3 mg of colorless oily liquid is obtained with a yield of 90%. 1 H NMR(400MHz, CDCl3) δ7.09(d,J=8.5Hz,2H),6.82(d,J=8.5Hz,2H),4.20(t,J=6.2Hz,2H),4.06 (t,J=6.0Hz,2H),2.84(t,J=7.5Hz,2H),2.77–2.67(m,2H),2.16(p,J=6.1Hz,2H),2.13(s,3H). 19 FNMR (376MHz, CDCl3) δ-123.1(dd,J=105.2,55.8Hz,1F),-130.2(dd,J=108.0,105.2Hz,1F),-134.5(dd,J=108.0,55.8Hz,1F). 13 C NMR (101MHz, CDCl3) δ208.1, 157.2, 146.0 (ddd, J=277.0, 269.0, 67.3Hz), 136.8 (ddd, J=260.6, 47.1, 39. 9Hz),133.5,129.3,114.6,71.1(d,J=2.5Hz),63.7,45.4,30.1,29.2,29.0.MS(DART,m / z):320.2(M+NH4 + ).HRMS(DART):m / z Calcd.for C 15 H 21 O3F3N + (M+NH4 + )320.1468, found 320.1473.

[0339] Embodiment 74

[0340] The specific compound prepared in Example 74 is

[0341] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 66.3 mg of colorless oily liquid is obtained with a yield of 86%. 1H NMR (400MHz, CDCl3) δ7.59 (d, J = 9.0 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 4.20 (td, J = 6.0, 1.6 Hz, 2H), 4.14 (t, J = 6.0 Hz, 2H), 2.21 (p, J = 6.0 Hz, 2H). 19 F NMR (376MHz, CDCl3) δ-122.7 (dd, J=104.7, 56.1Hz, 1F), -130.0 (dd, J=108.2, 104.8Hz, 1F), -134.7 (dd, J=108.1, 56.2Hz, 1F). 13 C NMR(101MHz, CDCl3) δ162.0,146.0(ddd,J=277.4,269.3,66.9Hz),136.8(ddd,J=261.0,47 .3,39.8Hz),134.1,119.2,104.3,70.7(d,J=2.6Hz),64.0,28.9.MS(DART,m / z):258.1(M+H + ).HRMS(DART):m / z Calcd.for C 12 H 11 O2F3N + (M+H + )258.0736, found 258.0744.

[0342] Embodiment 75

[0343] The specific compound prepared in Example 75 is

[0344] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 70.8 mg of colorless oily liquid is obtained with a yield of 78%. 1 H NMR (400MHz, CDCl3) δ6.84(d,J=8.7Hz,1H),6.88–6.79(m,2H),5.96(ddt,J=16.8,10.1,6.7Hz,1H),5.17–4.99(m, 2H), 4.23 (td, J=6.2, 1.4Hz, 2H), 4.12 (t, J=6.1Hz, 2H), 3.85 (s, 3H), 3.34 (d, J=6.6Hz, 2H), 2.21 (p, J=6.2Hz, 2H). 19F NMR (376MHz, CDCl3) δ-123.2 (dd, J=105.2, 55.7Hz, 1F), -130.3 (dd, J=107.8, 105.4Hz, 1F), -134.5 (dd, J=107.9, 55.7Hz, 1F). 13 C NMR (101MHz, CDCl3) δ149.8, 146.6, 146.1 (ddd, J=276.8, 269.3, 67.4Hz), 137.7, 136.8 (ddd, J=260.6, 47.1, 40.0Hz),133.7,120.7,115.8,114.3,112.6,71.3(d,J=2.2Hz),65.4,56.0,39.9,29.3.MS(EI,m / z,%):302(M + ,62.67),164(100),162(63.36),177(45.39),91(39.67).HRMS(EI):m / z Calcd.for C 15 H 17 O3F3(M)302.1130, found 302.1139.

[0345] Embodiment 76

[0346] The specific compound prepared in Example 76 is

[0347] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 66.3 mg of colorless oily liquid is obtained with a yield of 74%. 1 H NMR (400MHz, CDCl3) δ7.63(d,J=9.5Hz,1H),7.38(d,J=8.5,1H),6.89–6.76(m,2H),6.25( d, J=9.5Hz, 1H), 4.21 (td, J=6.1, 1.4Hz, 2H), 4.15 (t, J=6.0Hz, 2H), 2.22 (p, J=6.0Hz, 2H). 19 F NMR (376MHz, CDCl3) δ-122.8 (dd, J=104.7, 56.0Hz, 1F), -130.0 (dd, J=108.2, 104.7Hz, 1F), -134.6 (dd, J=108.1, 56.1Hz, 1F). 13C NMR (101MHz, CDCl3) δ161.9, 161.2, 155.9, 146.0 (ddd, J = 277.8, 269.5, 67.1Hz), 143.5, 136.8 (ddd, J = 260. 8,47.2,39.8Hz),128.9,113.3,112.83,112.75,101.6,70.8(d,J=2.4Hz),64.2,28.9.MS(EI,m / z,%):300(M + ,8.52),84(100),86(71.99),175(33.99),47(25.78).HRMS(EI):m / z Calcd.for C 14 H 11 O4F3(M)300.0609, found 300.0613.

[0348] Embodiment 77

[0349] The specific compound prepared in Example 77 is

[0350] The substrate was 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether, ethyl acetate (0.5 mL) was used as a co-solvent, the reaction time was 12 hours, and the fluorine spectrum yield was 77% (with trifluoromethyl phenyl ether as an internal standard). 19 F NMR(376MHz, CDCl3)δ-123.1(dd,J=105.4,55.7Hz,1F),-130.2(dd,J=107.8,105.5Hz,1F),-134.6(dd,J=107.9,55.6Hz,1F).MS(DART,m / z):569.4(M+H + ).HRMS(DART):m / z Calcd.for C 34 H 56 O3F3 + (M+H + )569.4176, found 569.4168.

[0351] Embodiment 78

[0352] The specific compound prepared in Example 78 is

[0353] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether. The reaction time is 12 hours. 83.5 mg of bright yellow solid is obtained with a yield of 87%. 1H NMR (400MHz, CDCl3) δ7.76 (d, J = 8.2Hz, 2H), 7.62 (t, J = 7.3Hz, 1H), 7.54 (t, J = 7. 3Hz,2H),4.15(s,1H),3.22–3.12(m,2H),3.11–3.01(m,2H),2.07–1.81(m,4H). 19 F NMR (376MHz, CDCl3) δ-121.6 (dd, J=103.0, 56.0Hz, 1F), -129.6 (dd, J=108.2, 103.0Hz, 1F), -132.6 (dd, J=108.2, 56.0Hz, 1F).

[0354] Embodiment 79

[0355] The specific compound prepared in Example 79 is

[0356] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether, the reaction time is 12 hours, and the fluorine spectrum yield is 31% (using trifluorotoluene as the internal standard, δ-63.0ppm). 19 F NMR (376MHz, CH3CN) δ-122.8 (dd, J=104.8, 55.2Hz, 1F), -130.7 (dd, J=107.1, 105.4Hz, 1F), -134.9 (dd, J=107.6, 55.4Hz, 1F).

[0357] Embodiment 80

[0358] The specific compound prepared in Example 80 is

[0359] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether, the reaction time is 12 hours, and the fluorine spectrum yield is 62% (using trifluorotoluene as the internal standard, δ-63.0ppm). 19 F NMR (376MHz, CH3CN) δ-123.9 (dd, J=104.7, 56.1Hz, 1F), -131.0 (m, 1F), -132.0 (dd, J=107.2, 56.1Hz, 1F).

[0360] Embodiment 81

[0361] The specific compound prepared in Example 81 is

[0362] The substrate is 2-bromo-1,1,2,2-tetrafluoroethyl alkyl ether, the reaction time is 12 hours, and the fluorine spectrum yield is 38% (using trifluorotoluene as the internal standard, δ-63.0ppm).19 F NMR (376MHz, CH3CN) δ-120.7 (dd, J=106.9, 53.6Hz, 1F), -122.4 (dd, J=103.9, 53.5Hz, 1F), -130.2 (t, J=105.3Hz, 1F).

[0363] Examples 82-86

[0364] Investigation of the effects of water, Lewis acid and other additives on the reaction

[0365]

[0366] In the glove box, zinc powder (4.9 mg, 0.075 mmol, 1.5 equiv) was weighed into a dried 25-mL sealed tube. After removing from the glove box, add (0.05mmol, 1.0equiv) and anhydrous CH3CN (1.0mL), and then a certain amount of additives were added. After heating at 95°C for 12 hours, trifluoromethyl phenyl ether was used as an internal standard and the fluorine spectrum was used for detection. The yield.

[0367] Example No. additive Fluorine spectrum yield Embodiment 82 <![CDATA[H2O(0.1mmol,2.0equiv)]]> 10％ Embodiment 83 <![CDATA[H2O(0.25mmol,5.0equiv)]]> 30％ Embodiment 84 <![CDATA[H2O(0.5mmol,10.0equiv)]]> 70％ Embodiment 85 <![CDATA[ZnCl2(0.09mmol,0.3equiv)]]> 85％ Embodiment 86 <![CDATA[Zn(OAc)2·2H2O(0.09mmol,0.3equiv)]]> 79％

[0368] Whether using acetonitrile that had just been treated by the solvent treatment system in the laboratory or the ultra-dry acetonitrile purchased from J&K, the target compound could not be obtained. It can be seen that the presence of water does have an effect on the reaction, and to a certain extent, the more water content, the higher the yield. A 70% yield can be obtained when 10 equivalents of water are added.

[0369] Embodiment 87

[0370] Formation of trifluoroethylene aryl ether from 2-bromo-1,1,2,2-tetrafluoroethyl aryl ether

[0371]

[0372] In the glove box, zinc powder (9.8 mg, 0.15 mmol, 1.5 equiv) was weighed into a dried 25-mL sealed tube. After removing from the glove box, add (0.1mmol, 1.0equiv) and anhydrous CH3CN (1.0mL), then zinc chloride (0.03mmol, 0.3equiv) was added. After heating at 95℃ for 12 hours, trifluoromethylphenyl ether was used as an internal standard (δ-60.0ppm) and the fluorescence spectrum was used for detection. The conversion rate was 100%, and the target product The yield was 52%, and the by-product The yield is 0.

[0373] As a control, without adding zinc chloride, the reaction was carried out under the same conditions as above for 12 hours. The conversion rate was 67%, and the target product The yield is 30%, and the by-product The yield is 4%.

[0374] Fluorine spectrum characterization data are as follows: δ-71.1(m,2F),-87.9(m,2F); δ-123.0(m,1F),-130.3(m,1F),-136.8(m,1F); δ-90.1(s,2F),-127.0(m,2F).

[0375] The method of the present invention is not only applicable to alkyl ether compounds, but also surprisingly found through research that it has better effects on non-alkyl ether substrates such as aryl ethers.

Claims

1. A method for preparing a 2-halogen-1,1,2,2-tetrafluoroethyl ether compound, characterized in that: It includes the following steps: In an organic solvent, in the presence of an initiator, a sodium salt and / or potassium salt of an alcohol compound represented by formula I is subjected to an etherification reaction with 1,2-dihalotetrafluoroethane represented by formula XCF2CF2X to obtain a 2-halogeno-1,1,2,2-tetrafluoroethyl ether compound represented by formula II; Wherein, X is the halogen, which is independently chlorine or bromine; M is sodium or potassium; R-for R y1 R y2 R y3 C-, substituted or unsubstituted C3-C 30 Cycloalkyl, substituted or unsubstituted 3-30-membered heterocycloalkyl; wherein the 3-30-membered heterocycloalkyl in the substituted or unsubstituted 3-30-membered heterocycloalkyl has 1-6 heteroatoms or heteroatom groups selected from O, N, S, S(═O) and S(═O)2; R y1 , R y2 , R y3 are independently D, substituted or unsubstituted C1-C 30 Alkyl, substituted or unsubstituted C2-C 30 Alkenyl, substituted or unsubstituted C2-C 30 Alkynyl, substituted or unsubstituted C3-C 30 Cycloalkyl, substituted or unsubstituted 3-30 membered heterocycloalkyl; substituted or unsubstituted C6-C 30 The substituted or unsubstituted 3-30-membered heterocycloalkyl group has 1-6 heteroatoms or heteroatom groups selected from O, N, S, S(═O)2; the substituted or unsubstituted 5-30-membered heteroaryl group has 1-6 heteroatoms selected from O, N and S; The substitution refers to the substitution of one or more hydrogen atoms on the group by a substituent R z Replace, each R z are independently: D, halogen, nitro, cyano, oxo, thio, -OH, -NH2, -COOH, -CHO, 1 or 2 substituted or unsubstituted C1-C 20 Alkyl-substituted amino, substituted or unsubstituted C1-C 20 Alkyl, substituted or unsubstituted C2-C 20 Alkenyl, substituted or unsubstituted C2-C 20 Alkynyl, substituted or unsubstituted C3-C 20 Cycloalkyl, substituted or unsubstituted 3-20 membered heterocycloalkyl; substituted or unsubstituted C6-C 20 aryl, substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted C1-C 20 Alkyl-substituted amino-Y-, substituted or unsubstituted C1-C 20 Alkyl-Y-, substituted or unsubstituted C2-C 20 Alkenyl-Y-, substituted or unsubstituted C2-C 20 Alkynyl-Y-, substituted or unsubstituted C3-C 20 Cycloalkyl-Y-, substituted or unsubstituted 3-20 membered heterocycloalkyl-Y-, substituted or unsubstituted C6-C 20 wherein Y- is independently: O-, S-, S(O)-, S(O)2-, Se-, Te-, S(O)2O-, C(O)-, OC(O)-, C(O)O-, NHC(O)-; the substituted or unsubstituted 3-20-membered heterocycloalkyl, the 3-20-membered heterocycloalkyl in the substituted or unsubstituted 3-20-membered heterocycloalkyl-Y- has 1-5 heteroatoms or heteroatom groups selected from O, N, S, S(=O)2; the substituted or unsubstituted 5-20-membered heteroaryl, the 5-20-membered heteroaryl in the substituted or unsubstituted 5-20-membered heteroaryl-Y- has 1-5 heteroatoms selected from O, N and S; The substituent R z The substitution on R z One or more hydrogen atoms on the x Replace, each R x are independently: D, halogen, nitro, cyano, oxo, thio, -OH, -NH2, -COOH, -CHO, 1 or 2 C1-C 10 Alkyl substituted amino, halogenated or oxo or unsubstituted C1-C 10 Alkyl, halogenated or unsubstituted C2-C 10 Alkenyl, halogenated or unsubstituted C2-C 10 Alkynyl, halogenated or oxo or unsubstituted C3-C 10 Cycloalkyl, halogenated or oxo-substituted or unsubstituted 3-10 membered heterocycloalkyl; halogenated or unsubstituted C6-C 10 aryl, halogenated or unsubstituted 5-10 membered heteroaryl, 1 or 2 C1-C 10 Alkyl-substituted amino-Z-, halogenated or unsubstituted C1-C 10 Alkyl-Z-, halogenated or unsubstituted C2-C 10 Alkenyl-Z-, halogenated or unsubstituted C2-C 10 Alkynyl-Z-, halogenated or unsubstituted C3-C 10 Cycloalkyl-Z-, halogenated or unsubstituted 3-10 membered heterocycloalkyl-Z-, halogenated or unsubstituted C6-C 10 wherein each Z- is independently: C1-C6 alkylene, O-, S-, S(O)-, S(O)2-, Se-, Te-, S(O)2O-, C(O)-, OC(O)-, C(O)O-, NHC(O)-; the substituted or unsubstituted 3-10 membered heterocycloalkyl, the 3-10 membered heterocycloalkyl in the substituted or unsubstituted 3-10 membered heterocycloalkyl-Z- has 1-4 heteroatoms or heteroatom groups selected from O, N, S, S(=O)2; the substituted or unsubstituted 5-10 membered heteroaryl, the 5-10 membered heteroaryl in the substituted or unsubstituted 5-10 membered heteroaryl-Z- has 1-4 heteroatoms selected from O, N and S; The organic solvent is an amide solvent; The initiator is zinc powder.

2. The method for preparing the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound according to claim 1, characterized in that: It meets one or more of the following conditions: (1) The 1,2-dihalotetrafluoroethane is 1,2-dibromotetrafluoroethane, 1,2-dichlorotetrafluoroethane, 1-bromo-2-chlorotetrafluoroethane, or a combination thereof; (2) The molar ratio of the sodium salt and / or potassium salt of the alcohol compound to the 1,2-dihalotetrafluoroethane is 1:1 to 1:10; (3) The molar ratio of the sodium salt and / or potassium salt of the alcohol compound to the initiator is 1:0.01 to 1:1; (4) The molar volume ratio of the alcohol compound to the solvent is 0.01 mol / L to 1 mol / L; (5) The preparation method also includes a preparation method of the sodium salt and / or potassium salt of the alcohol compound, which comprises the following steps: in an organic solvent, the alcohol compound is subjected to a salt-forming reaction with a base to obtain the sodium salt and / or potassium salt of the alcohol compound, wherein the base is a sodium and / or potassium base; or, the preparation method of the 2-halogeno-1,1,2,2-tetrafluoroethyl ether compound, which comprises the following steps: in the organic solvent, in the presence of the initiator and the base, the alcohol compound is subjected to an etherification reaction with 1,2-dihalotetrafluoroethane to obtain the 2-halogeno-1,1,2,2-tetrafluoroethyl ether compound.

3. The method for preparing the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound according to claim 2, characterized in that: It meets one or more of the following conditions: (1) The amide solvent is DMF; (2) The 1,2-dihalotetrafluoroethane is 1,2-dibromotetrafluoroethane; (3) The molar ratio of the sodium salt and / or potassium salt of the alcohol compound to the 1,2-dihalotetrafluoroethane is 1:3 to 1:4; (4) The molar ratio of the sodium salt and / or potassium salt of the alcohol compound to the initiator is 1:0.1 to 1:0.5; (5) The molar volume ratio of the alcohol compound to the solvent is 0.1±0.05 mol / L; (6) The temperature of the etherification reaction is -10 to 35°C; (7) In the method for preparing the sodium salt and / or potassium salt of the alcohol compound, the base is: sodium, potassium, NaH, KH, sodium methoxide, potassium methoxide, sodium tert-butoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, or a combination thereof; (8) In the method for preparing the sodium salt and / or potassium salt of the alcohol compound, the molar ratio of the alcohol compound to the base is 1:1 to 1:4; (9) In the method for preparing the sodium salt and / or potassium salt of the alcohol compound, the organic solvent is as shown in the organic solvent in the etherification reaction and is independently the same or different; (10) In the method for preparing the sodium salt and / or potassium salt of the alcohol compound, the temperature of the salt-forming reaction is -40 to 80°C; (11) After the salt-forming reaction is completed, the etherification reaction is directly carried out without any further treatment.

4. The method for preparing the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound according to claim 3, characterized in that: It meets one or more of the following conditions: (1) In the method for preparing the sodium salt and / or potassium salt of the alcohol compound, the base is NaH; (2) In the method for preparing the sodium salt and / or potassium salt of the alcohol compound, the molar ratio of the alcohol compound to the base is 1:2 to 1:3; (3) In the method for preparing the sodium salt and / or potassium salt of the alcohol compound, the temperature of the salt-forming reaction is -10 to 35°C; (4) the alcohol compound corresponding to the sodium salt and / or potassium salt of the alcohol compound comprises one or more hydroxyl groups selected from the group consisting of a primary hydroxyl group, a secondary hydroxyl group and a tertiary hydroxyl group; (5) In the alcohol compound corresponding to the sodium salt and / or potassium salt of the alcohol compound, the β position of the alcohol hydroxyl group is not directly substituted by O, S or F.

5. The method for preparing 2-halogen-1,1,2,2-tetrafluoroethyl ether compounds according to claim 4, characterized in that: The 2-halogen-1,1,2,2-tetrafluoroethyl ether compound is any one of the following:

6. A method for preparing a trifluorovinyl ether compound, characterized in that: It includes the following steps: In an organic solvent, in the presence of an initiator, a 2-halogen-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula III and a reducing agent are subjected to a dehalogenation reaction to obtain a trifluorovinyl ether compound containing a fragment as shown in formula IV; the initiator is: zinc salt, water, or a combination thereof; Wherein, X is the halogen, which is independently chlorine or bromine; The reducing agent is zinc powder, iron powder, or a combination thereof; The method comprises the steps of the method for preparing the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound as described in any one of claims 1 to 5.

7. The method for preparing trifluorovinyl ether compounds according to claim 6, characterized in that: It meets one or more of the following conditions: (1) The organic solvent is an aromatic hydrocarbon solvent, a nitrile solvent, an ether solvent, an ester solvent, an alcohol solvent, an amide solvent, a sulfoxide solvent, or a combination thereof; (2) The zinc salt is zinc chloride, zinc acetate, or a hydrate thereof; (3) When the initiator is a zinc salt or a hydrate thereof, the molar ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the initiator is 1:0.01 to 1:10; (4) When the initiator is water, the molar ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the initiator is 1:(10±1); (5) The molar ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the reducing agent is 1:1 to 1:10; (6) The molar volume ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the organic solvent is 0.01 mol / L to 0.5 mol / L; (7) The temperature of the dehalogenation reaction is room temperature to 120°C; (8) In the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula III and the corresponding trifluorovinyl ether compound containing a fragment as shown in formula IV, the C connected to the -O- is a C atom in an alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl or heteroaryl group.

8. The method for preparing trifluorovinyl ether compounds according to claim 6, characterized in that: It meets one or more of the following conditions: (1) When the organic solvent is an aromatic hydrocarbon solvent, the aromatic hydrocarbon solvent is toluene; (2) When the organic solvent is a nitrile solvent, the nitrile solvent is acetonitrile and / or benzonitrile; (3) When the organic solvent is an ether solvent, the ether solvent is one or more of tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether and methyl tert-butyl ether; (4) When the organic solvent is an ester solvent, the ester solvent is ethyl acetate; (5) When the organic solvent is an amide solvent, the amide solvent is DMF; (6) When the organic solvent is a sulfoxide solvent, the sulfoxide solvent is DMSO; (7) When the organic solvent is an alcohol solvent, the alcohol solvent is one or more of methanol, ethanol, isopropanol and tert-butanol; (8) The initiator is zinc chloride, zinc acetate dihydrate or water; (9) When the initiator is a zinc salt or a hydrate thereof, the molar ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the initiator is 1:(0.3±0.1); (10) The reducing agent is zinc powder; (11) The molar ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the reducing agent is 1:(1.5±0.2); (12) The molar volume ratio of the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound to the organic solvent is 0.05±0.05 mol / L; (13) The temperature of the dehalogenation reaction is 40 to 100°C; (14) In the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula III and the corresponding trifluorovinyl ether compound containing a fragment as shown in formula IV, when the C connected to -O- is an alkyl C, the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in formula III is represented by the formula R-OCF2CF2X as described in claim 1; (15) When the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound containing a fragment as shown in Formula III and the corresponding trifluorovinyl ether compound containing a fragment as shown in Formula IV, the C connected to -O- is a C atom in an aromatic group, and the aromatic group is a substituted or unsubstituted C6-C 30 The substitution refers to the substitution of one or more hydrogen atoms on the aryl group by a substituent R a Replace, each R a are independently: halogen, cyano, -OH, -NH2, 1 or 2 substituted or unsubstituted C1-C 20 Alkyl-substituted amino, substituted or unsubstituted C1-C 20 Alkyl, substituted or unsubstituted C2-C 20 Alkenyl, substituted or unsubstituted C2-C 20 Alkynyl, substituted or unsubstituted C3-C 20 Cycloalkyl, substituted or unsubstituted 3-20 membered heterocycloalkyl; substituted or unsubstituted C6-C 20 aryl, substituted or unsubstituted 5-20 membered heteroaryl, substituted or unsubstituted C1-C 20 Alkyl-substituted amino-M-, substituted or unsubstituted C1-C 20 Alkyl-M-, substituted or unsubstituted C2-C 20 Alkenyl-M-, substituted or unsubstituted C2-C 20 Alkynyl-M-, substituted or unsubstituted C3-C 20 Cycloalkyl-M-, substituted or unsubstituted 3-20 membered heterocycloalkyl-M-, substituted or unsubstituted C6-C 20 wherein M- is independently: O-, S-, S(O)2-, S(O)2O-, OC(O)-, C(O)O-, NHC(O)-; the substituted or unsubstituted 3-20-membered heterocycloalkyl, the 3-20-membered heterocycloalkyl in the substituted or unsubstituted 3-20-membered heterocycloalkyl-M- has 1-5 heteroatoms or heteroatom groups selected from O, N, and S; the substituted or unsubstituted 5-20-membered heteroaryl, the 5-20-membered heteroaryl in the substituted or unsubstituted 5-20-membered heteroaryl-M- has 1-5 heteroatoms selected from O, N, and S; The substituent R a The substitution on R a One or more hydrogen atoms on the z Replacement, where R z The definition is as shown in claim 1.

9. Use of a 2-halogen-1,1,2,2-tetrafluoroethyl ether compound in the preparation of a trifluorovinyl ether compound; characterized in that: in, The 2-halogen-1,1,2,2-tetrafluoroethyl ether compound is shown in the formula R'-OCF2CF2X, Wherein, the definition of X is as described in claim 1; the definition of R' is as described in claim 1; And the formula R'-OCF2CF2X is not the following compound: CH3OCF2CF2Br, CF3(CF2)7CH2OCF2CF2Br, BrCF2CF2OCH2CF2OCF2CF2OCF2CF2OCF2CF2CFCF3, BrCFCF2OCH(Me)CH2CH2CH(Me)OCF2CF2H, BrCF2CF2OC H(Me)CH2CH2CH(Me)OCF2CF2Br, BrCF2CF2OCH(Me)CH2CH2CH2CH2CH(Me)OCF2CF2H, BrCF2CF2OC(CF3)3, BrCF2CF2OC(CF3)2CF2CF3, CH3OCF2CF2Cl, CF3CH2OCF2CF2Cl, NO2CF2CH2OCF2CF2Cl, ClCF2CF2OCH2(OF2)2CF2H, ClCF2CF2OCH2(CF2)5CF2H, ClCF2CF2OCH(CF3)2, ClCF2CF2OC(CH3)3, CICF2CF2OC(CF3)3, ClCF2CF2OCH2CF2CF2CF=CF2, which includes the steps in the preparation method of 2-halogen-1,1,2,2-tetrafluoroethyl ether compounds as described in any one of claims 1 to 5.

10. The use according to claim 9, characterized in that It includes the following steps: In an organic solvent, in the presence of an initiator, the 2-halogen-1,1,2,2-tetrafluoroethyl ether compound and a reducing agent are subjected to a dehalogenation reaction to obtain a trifluorovinyl ether compound as shown in formula V; the initiator is: zinc salt, water, or a combination thereof; Wherein, the operation and reaction conditions of the dehalogenation reaction may be as shown in the operation and reaction conditions of the preparation method of trifluorovinyl alkyl ether according to any one of claims 6 to 8; R' is defined as in claim 9.

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