A method for preparing trifluoromethyl olefins

Abstract

This invention discloses a method for preparing trifluoromethyl olefins. The method comprises the following steps: (1) in a haloalkane solvent or ether solvent, a compound as shown in Formula I, CuX'2, CF3SO2Na, N(R) 2 (1) 4X undergoes the addition reaction shown below; (2) The product of the addition reaction in step (1) is reacted with a base in an organic solvent to undergo the elimination reaction shown below. The preparation method of trifluoromethyl olefins provided by the present invention has the advantages of being applicable to electron-rich styrene substrates, requiring less metal catalyst, not requiring high pressure conditions, not requiring photocatalysis, having easy-to-control reaction conditions, being relatively convenient for post-processing, and having a high yield.

Description

Technical Field

[0001] This invention relates to a method for preparing trifluoromethyl olefins. Background Technology

[0002] Trifluoromethylene, as a fluorine-containing structure, has been studied in fluorine chemistry due to its applications in drug activity and reaction intermediates. Among them, acylated enol derivatives (1a) used as elastase inhibitors or elastase inhibitor prodrugs and the dopamine transporter DAT (1b) both contain the structure of trifluoromethylene.

[0003]

[0004] Meanwhile, trifluoromethyl olefins can also participate in reactions efficiently as reaction intermediates. Their structures can not only undergo halogenation, oxidation and elimination reactions, but also introduce formamide groups, as shown below.

[0005]

[0006] Many researchers have conducted studies on the preparation methods of trifluoromethyl alkenes. Haszeldine reacts alkynes with iodine trifluoride to produce trifluoromethyl-substituted alkenes (Haszeldine [Journal of the Chemical Society, 1952, pp. 3490, 3495]). This method uses Cu and Hg salts to complete the reaction under photocatalysis; however, the preparation of iodine trifluoride is difficult and the reaction conditions are harsh.

[0007]

[0008] Shang et al. prepared trifluoromethyl olefins from aromatic alkynes under NaBrO3 catalysis and with water and dichloromethane as solvents at 110 °C for 24 h (Free-radical promoted bromotrifluoromethylation of arylalkynes with CF3SO2Na and NaBrO3 Shang, Xiao-Jie; Luo, Rui; Zhu, Jing; Liu, Zhong-Quan [Tetrahedron Letters, 2021, vol. 62, art. no. 152683]). This preparation method is limited to arylalkynes as substrates and is not applicable to electron-withdrawing alkynes and aliphatic alkynes. Furthermore, the reaction temperature is high, the reaction time is long, the yield is low, and the products obtained are mostly E-configured olefins.

[0009]

[0010] Yan Xueyu et al. used Langlois reagent (CF3SO2Na) to induce trifluoromethylation of olefins, followed by elimination reaction using DBU to generate olefins with trifluoromethyl groups. This reaction, using CuX2 (≥2.4 equivalents) as the halogen source and catalyst, and CF3SO2Na as the trifluoromethyl source, achieved the chloro(bromination)trifluoromethylation of olefins. The advantages of this reaction are its simplicity, readily available starting materials, and applicability not only to styrene substrates but also to common unactivated olefins. The disadvantage is that it is not applicable to electron-rich styrene substrates. Mechanistic experiments showed that CF3SO2Na undergoes a single-electron transfer reaction with CuX2 (X = Cl, Br) to generate a trifluoromethyl radical, which is then captured by the olefin. Furthermore, based on the developed olefin bromination trifluoromethylation reaction, the addition of DBU yields the corresponding trifluoromethyl-substituted olefin products, thus achieving a one-pot, two-step olefin trifluoromethylation process. No separation is required during the reaction, making the operation simple and the products all being trans-olefins. However, the reaction has the disadvantage of moderate yield and is not suitable for styrene substrates with electron-donating groups.

[0011]

[0012] Existing technologies for the trifluoromethylation of olefins have several drawbacks, including the inapplicability of electron-rich styrene substrates, the requirement for large amounts of copper halides (≥2.4 equivalents), the need for high pressure during the reaction, and low yields. These problems urgently need to be addressed. Summary of the Invention

[0013] The technical problem this invention aims to solve is to overcome the shortcomings of existing methods for preparing trifluoromethylolefins from olefin compounds, such as the inapplicability of electron-rich styrene substrates, the large amount of copper halide required (≥2.4 equivalents), the need for high-pressure reactions, and generally low yields. This invention provides a method for preparing trifluoromethylolefins. Compared with existing technologies, this method has advantages such as applicability of electron-rich styrene substrates, low metal catalyst usage, no need for high-pressure conditions, no need for photocatalysis, easy control of reaction conditions, convenient post-processing, and high overall yield.

[0014] The present invention solves the above-mentioned technical problems through the following technical solutions.

[0015] This invention provides a method for preparing the compound shown in Formula II, comprising the following steps: in an organic solvent, mixing the compound shown in Formula I, CuX'2, CF3SO2Na, and N(R) 2 4X can undergo the addition reaction shown below;

[0016]

[0017] Where X, X', and X” are halogens independently;

[0018] R 1 For C1-C 15 Alkyl, C6-C 10 aryl, 5-10 heteroaryl, with one or more R 1-1 Replacement C6-C 10 aryl or aryl with one or more R 1-2 The substituted 5-10-membered heteroaryl group, wherein the heteroatom in the heteroaryl group is selected from one or more of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4;

[0019] R 1-1 and R 1-2 It is independently C1-C6 alkyl, halogen, or nitro;

[0020] R 2 It is independently a C1-C6 alkyl group.

[0021] In one embodiment of the present invention, the halogen in X, X' and X” can be F, Cl, Br or I, preferably Cl or Br.

[0022] In one embodiment of the present invention, R 1 In the context, C1-C 15 Alkyl groups can be C1-C 12 Alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, and n-decyl.

[0023] In one embodiment of the present invention, R 1 In the context of C6-C 10 The aryl group can be phenyl or naphthyl.

[0024] In one embodiment of the present invention, R 1 In the context, the one or more R 1-1 Replacement C6-C 10 C6-C in aryl 10 The aryl group can be phenyl or naphthyl.

[0025] In one embodiment of the present invention, R 1 In this context, the 5-10 membered heteroaryl group can be... (For example )or (For example ).

[0026] In one embodiment of the present invention, R 1 In the context, the one or more R 1-2 The heteroaryl group in the substituted 5-10 quinone heteroaryl group can be (For example )or (For example ).

[0027] In one embodiment of the present invention, R 1-1 and R 1-2 In this context, the C1-C6 alkyl group can be a C1-C4 alkyl group, such as methyl, ethyl, n-propyl, n-butyl, isopropyl, or tert-butyl.

[0028] In one embodiment of the present invention, R 1-1 and R 1-2 In this context, the halogen can be F, Cl, Br, or I.

[0029] In one embodiment of the present invention, R 2 In this context, the C1-C6 alkyl group can be a C1-C4 alkyl group, such as methyl, ethyl, propyl, or butyl.

[0030] In one embodiment of the present invention, the compound represented by Formula I is selected from any of the following structures:

[0031]

[0032] In one embodiment of the present invention, in the addition reaction, X” in the compound represented by formula II originates from (N(R) 2 X in )4X) or X' in CuX'2.

[0033] In one embodiment of the present invention, the addition reaction is carried out under oxygen conditions.

[0034] In one embodiment of the present invention, the organic solvent may be an organic solvent conventionally used in this type of reaction in the art, preferably a halogenated hydrocarbon solvent and / or an ether solvent. The halogenated hydrocarbon solvent may be one or more of dichloromethane, trichloromethane, and carbon tetrachloride, preferably dichloromethane. The ether solvent may be one or more of diethyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, and dioxane, preferably ethylene glycol dimethyl ether and / or dioxane.

[0035] In one embodiment of the present invention, CuX'2 may be one or more of fluorinated ketones, copper chloride, copper bromide and copper iodide, preferably copper bromide and / or copper chloride, and more preferably copper chloride.

[0036] In one embodiment of the present invention, the amount of organic solvent used can be the amount conventionally used for this type of reaction in the art, as long as it does not affect the reaction; preferably, the molar concentration of the compound shown in Formula I in the organic solvent is 0.01 to 1 mol / L, more preferably 0.1 mol / L.

[0037] In one embodiment of the present invention, the molar ratio of the compound as shown in Formula I to CF3SO2Na can be 1:(1-4), preferably 1:(1-2), and more preferably 1:1.1.

[0038] In one embodiment of the present invention, the molar ratio of the compound as shown in Formula I to CuX'2 can be 1:(0.01-1), preferably 1:(0.05-0.5), and more preferably 1:0.11.

[0039] In one embodiment of the present invention, the molar ratio of CF3SO2Na to CuX'2 can be 1:(0.05-1), preferably 1:0.1.

[0040] In one embodiment of the present invention, the temperature of the addition reaction can be the conventional reaction temperature for this type of reaction in the art, preferably 50-120°C, more preferably 60-100°C, and even more preferably 80°C.

[0041] In one embodiment of the present invention, the reaction time of the addition reaction is the conventional reaction time for this type of reaction in the art, preferably 2-48h, more preferably 4-24h, and even more preferably 24h.

[0042] In one embodiment of the present invention, the addition reaction satisfies all of the following conditions:

[0043] (1) The organic solvent is dioxane;

[0044] (2) The CuX'2 mentioned above is copper chloride;

[0045] (3) The molar concentration of the compound of formula I in the organic solvent is 0.1 mol / L;

[0046] (4) The molar ratio of the compound shown in Formula I to CF3SO2Na is 1:1.1;

[0047] (5) The molar ratio of the compound shown in Formula I to CuX'2 is 1:0.11;

[0048] (6) The molar ratio of CF3SO2Na to CuX'2 is 1:0.1;

[0049] (7) The temperature of the addition reaction is 80℃.

[0050] This invention also provides a method for preparing trifluoromethyl olefins, which includes the following steps:

[0051] (1) The compound shown in Formula II can be obtained by carrying out an addition reaction according to the preparation method of the compound shown in Formula II as described above;

[0052] (2) The compound of formula II prepared in step (1) is reacted with a base in an organic solvent to carry out the elimination reaction shown below to obtain the compound of formula III.

[0053]

[0054] In one embodiment of the present invention, after the reaction in step (1) is completed, the organic solvent is removed before proceeding to step (2).

[0055] In one embodiment of the present invention, in step (1), the method for removing the organic solvent is a conventional method for removing organic solvent in the art, such as rotary evaporation;

[0056] In one embodiment of the present invention, in step (2), the base may be a base commonly used in this type of reaction in the art, such as DBU.

[0057] In one embodiment of the present invention, in step (2), the organic solvent may be an organic solvent commonly used in this type of reaction in the art, preferably a halogenated hydrocarbon solvent, such as dichloromethane.

[0058] In one embodiment of the present invention, in step (2), the reaction is carried out under closed conditions, such as in a sealed tube.

[0059] In one embodiment of the present invention, in step (2), the reaction temperature in the elimination reaction can be the conventional reaction temperature of this type of reaction in the art, preferably 60-120°C, for example 80°C.

[0060] In one embodiment of the present invention, in step (2), the amount of organic solvent used can be the amount conventional for this type of reaction in the art, so as not to affect the reaction; the molar concentration of the compound containing the compound shown in Formula II in the organic solvent is 0.01 to 1 mol / L, for example 0.1 mol / L.

[0061] In one embodiment of the present invention, the molar ratio of the compound of formula I to the base described in step (2) may be 1:(1-3), preferably 1:(1.5-2.5), for example 1:2.

[0062] In one embodiment of the present invention, after the addition reaction in step (1) is completed, the organic solvent is removed to obtain a crude product, and the crude product is then reacted with the base in the organic solvent to carry out an elimination reaction.

[0063] Certain chemical groups defined herein are preceded by simplified symbols to indicate the total number of carbon atoms present in the group. For example, C1-C6 alkyl refers to an alkyl group having a total of 1, 2, 3, 4, 5, or 6 carbon atoms as defined below. The total number of carbon atoms in the simplified symbols does not include carbons that may be present in substituents of the group.

[0064] In this paper, the numerical ranges defined in the substituents, such as 0 to 4, 1-4, 1 to 3, etc., indicate the integers within that range, such as 1-6 being 1, 2, 3, 4, 5, 6.

[0065] Except as otherwise specified, when used in the specification and claims of this application, the following terms shall have the following meanings.

[0066] The terms “one or more” or “one or more kinds” refer to 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.

[0067] The term "comprising" is an open-ended expression, meaning it includes the contents specified in this invention, but does not exclude other aspects.

[0068] The term "substituted" refers to the substitution of one or more hydrogen atoms on a particular atom by a substituent, including deuterium and hydrogen variants, provided that the valence state of the particular atom is normal and the substituted compound is stable.

[0069] Generally, the term "substituted" indicates that one or more hydrogen atoms in a given structure are substituted by a specific substituent. Further, when the group is substituted by more than one of the substituents, the substituents are independent of each other; that is, the more than one substituent can be different or the same. Unless otherwise indicated, a substituent can be substituted at each substituted position of the substituted group. When more than one position in a given structural formula can be substituted by one or more substituents selected from a specific group, the substituents can be substituted at the same or different positions.

[0070] Term "C" x -C y "Alkyl" refers to a straight-chain or branched saturated hydrocarbon containing x to y carbon atoms. For example, the terms "C1-C6 alkyl" or "C 1-6 "alkyl" specifically refers to independently disclosed methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and C6 alkyl; "C" 1-4 "Alkyl" specifically refers to independently disclosed methyl, ethyl, C3 alkyl (i.e. propyl, including n-propyl and isopropyl), and C4 alkyl (i.e. butyl, including n-butyl, isobutyl, sec-butyl, and tert-butyl).

[0071] The term "aryl" refers to a group having 6-14 ring atoms and providing zero heteroatoms in an aromatic ring system. It is a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g., having 6, 10, or 14 shared p electrons in a cyclic array). 14Aryl group ("aryl"). Examples of the above aryl units include phenyl, naphthyl, phenanthryl, or anthracene.

[0072] The term "heteroaryl" refers to a group having a carbon atom and 1-3 heteroatoms (each heteroatom independently selected from nitrogen, oxygen, and sulfur) in a 5-16 member monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 shared p electrons in a cyclic array). In heteroaryl groups containing one or more nitrogen atoms, the linking point can be either a carbon or a nitrogen atom, provided the valence allows.

[0073] Exemplary 5-membered heteroaryl groups include, but are not limited to: pyrrole, furanyl, thiophene, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiazolyl, furazolyl, oxtriazolyl, or tetrazolyl. Exemplary 6-membered heteroaryl groups include, but are not limited to: pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, triazinyl, or tetraazinyl.

[0074] The term "halogen" is selected from F, Cl, Br or I, especially Br or Cl.

[0075] Without violating common sense in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0076] The reagents and raw materials used in this invention are all commercially available.

[0077] The significant advantages of this invention are as follows: the preparation method uses olefins as reaction substrates and readily available CF3SO2Na as trifluoromethylating reagents, in combination with copper halides to prepare trifluoromethylated olefins. This preparation method is simple to operate, requires no photocatalysis, has convenient post-processing, and offers a wide range of substrate applicability or yields ranging from moderate to excellent. Detailed Implementation

[0078] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0079] Instrument Information: 1 H NMR spectra were measured using a Bruker AM-300 (300MHz) and a Varian VXR (400MHz) NMR spectrometer, with TMS as an internal standard. 19 F NMR spectra were measured using a Bruker AM-300 (282MHz) and a Varian VXR (282MHz) NMR spectrometer, with FCCl3 as an internal standard and high field as negative. 13C10 NMR spectra were determined using a Bruker AM-400 (100Hz) and a Varian VXR (100Hz) NMR spectra; MS-EI spectra were determined using an Agilent 5973N and HP5989A mass spectrometer; HRMS-EI spectra were determined using a Waters GCT CA 176 mass spectrometer; column chromatography used silica gel (300-400 mesh) produced by Yantai Chemical Plant. Unless otherwise specified, all solvents and reagents used were commercially available. Purification was performed according to D.D. Perrin, W.F. Armarego, D.D. Perrin, Purification of Laboratory Chemicals, Pergamon: Oxford, 1997. TABC is an abbreviation for n-butylammonium chloride.

[0080] Example 1

[0081] Solvent and temperature selection

[0082]

[0083] Table 1

[0084] Serial Number reactants solvent Temperature / °C reaction results 1 styrene DMF 40 / 2 styrene DMF 80 / 3 styrene DMF 120 / 4 styrene Dioxane 40 / 5 styrene Dioxane 80 √ 6 styrene DMF 40 /

[0085] Reaction conditions: Sodium trifluorosulfite (1.1 mmol), copper chloride (0.11 mmol), styrene (1 mmol), tetrabutylammonium chloride (1.1 mmol), and 3 ml of solvent were added sequentially to a 10 ml Shrek tube under nitrogen protection. The oxygen was then removed, and the reaction was carried out for 6 h at different temperatures in an oxygen atmosphere.

[0086] TLC analysis revealed that the reaction proceeded successfully in dioxane as a solvent at 80°C.

[0087] Example 2

[0088] Screening was conducted on reaction time and the amount of copper chloride used.

[0089] Except for the conditions specifically specified in Table 2 below, all other conditions and procedures were the same as those in Example 1. After the reaction was completed, compound A was obtained by column chromatography. 1 H NMR (400MHz, CDCl3) δ7.89(d,J=7.8Hz,1H),7.59(s,1H),7.47(d,J=8.0Hz,1H),7.41–7.07(m,2H),4.98(s,1H).

[0090] Table 2

[0091]

[0092] Note: a The yield was the standard yield, and the absorption peak of the product was determined by trifluorotoluene. 19 The non-separation yield was calculated after F NMR.

[0093] When the amount of copper chloride was 0.2 eq, the reaction yield reached 85% after the reaction time was increased to 24 h. Subsequently, we reduced the amount of copper chloride to 0.1 eq and the reaction time was 24 h. The reaction still maintained a considerable yield. However, when the amount of catalyst was reduced to 0.05 eq, the yield could not be guaranteed. Therefore, the reaction conditions were: using dioxane as solvent, 0.1 eq of copper chloride, and reacting for 24 h.

[0094] Example 3

[0095] In a 10 ml Shrek tube, under nitrogen protection, sodium trifluorosulfite (1.1 mmol), copper chloride (0.11 mmol), styrene (1 mmol), tetrabutylammonium chloride (1.1 mmol), and 3 ml of dioxane were added sequentially. The oxygen was then removed, and the reaction was carried out at 80 °C in an oxygen atmosphere for 24 h. After the reaction, the reaction solution was extracted with dichloromethane and H₂O. The organic phase was then removed by rotary evaporation to obtain the crude product. The crude product, DBU (2.0 mmol), and 2 ml of dichloromethane were added to a 5 ml sealed tube, and the reaction was carried out at 80 °C for 2 h. The trans-elimination product was obtained by column chromatography.

[0096]

[0097] (E)-3,3,3-trifluoromethyl-1-naphthylpropene, colorless oily liquid (yield: 68%) 19 F NMR (376MHz, CDCl3) δ-63.1 (dd, J=6.6, 1.9Hz). 1 H NMR (400MHz, CDCl3) δ7.87–7.81 (m, 4H), 7.60–7.49 (m, 3H), δ7.31 (dq, J=16.1, 2.0Hz, 1H), 6.32 (dq, J=16.1, 6.5Hz, 1H) 13 C NMR(101MHz, CDCl3)δ137.8(q,J=6.8Hz),134.1(s),133.3(s),130.9(s),129.1(s),128.8(s),1 28.5(s),127.8(s),127.2(s),126.8(s),123.8(q,J=268.9Hz),123.1(s),116.0(q,J=33.8Hz).

[0098]

[0099] The compounds in Examples 4-16 below were obtained by the preparation method in Example 3.

[0100] Example 4

[0101] (E)-3,3,3-trifluoromethyl-1-phenylpropene, colorless oily liquid (yield: 79%) 19 F NMR (376MHz, CDCl3) δ-63.45 (dd, J=6.5, 2.0Hz). 1 H NMR (400MHz, CDCl3) δ7.52–7.44(m,2H),7.44–7.36(m,3H),7.17(dd,J=16.2,1.9Hz,1H),6.29–6.16(m,1H). 13 C NMR (101MHz, CDCl3) δ137.71(q,J=6.8Hz,),133.39(s),130.01(s),128.91(s,),127.50(s),124.99(s),122.46–122.08(s),115.74(q,J=33.8Hz).

[0102] Example 5

[0103]

[0104] (E)-3,3,3-trifluoromethyl-1-thiophenepropene, yellow oily liquid (yield: 59%) 19 F NMR(376MHz, CDCl3)δ-63.10–-63.17(m,1H). 1 H NMR (400MHz, CDCl3), 7.29 (dd, J = 7.6, 4.5Hz, 1H), 7.27 (d, 1H), 7.20 (t, J = 5.7Hz, 1H), 7.06 (dd, J = 5.0, 3.7Hz, 1H), 6.05 (dq, J = 15.8, 6.6Hz, 1H). 13 C NMR(101MHz, CDCl3)δ138.02(s),130.52(q,J=7.2Hz),129.98(s),127.91(s),127.72(s),124.77(s),122.11(s)

[0105] Example 6

[0106]

[0107] (E)-1-Methyl-2-(3,3,3-trifluoromethyl-1-propenyl)benzene, yellow oily liquid (yield: 58%) 19 FNMR (376MHz, CDCl3) δ-63.34 (dd, J=8.6, 4.3Hz). 1 H NMR(400MHz, CDCl3)δ7.48(d,J=8.1Hz,1H),7.47–7.45(m,1H),7.44–7.38(m,1H),7 .28(ddd,J=24.3,11.4,4.5Hz,2H),6.14(dq,J=16.0,6.5Hz,1H),1.37–1.18(t,3H). 13 C NMR(101MHz, CDCl3)δ136.93(s),135.53(q,J=6.8Hz,),132.56(s),130.72(s,),129.7 6(s,),126.42(s),126.17(s),123.57(d,J=269.1Hz),117.06(q,J=33.6Hz),19.60(s).

[0108] Example 7

[0109]

[0110] (E)-1-Methyl-3-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 64%). 19 FNMR (376MHz, CDCl3) δ-63.30 (dd, J=6.5, 2.1Hz). 1 H NMR(400MHz, CDCl3)δ7.30(dd,J=12.0,5.1Hz,1H),7.25–7.20(m,1H),7.17(dd, J=4.2,2.1Hz,2H),7.13(dd,J=4.2,2.0Hz,2H),6.37–6.07(m,1H),3.73(t,3H). 13 CNMR(101MHz, CDCl3)δ138.65(s),137.80(q,J=6.7Hz,),133.36(s),130.81(s), 128.80(s),128.17(s),124.70(s),122.37(s),115.58(q,J=33.7Hz),21.26(s).

[0111] Example 8

[0112]

[0113] (E)-1-Methyl-4-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 70%). 19 FNMR (376MHz, CDCl3) δ-63.14 (dd, J=6.6, 2.0Hz). 1 H NMR (400MHz, CDCl3) δ7.37(d,J=8.1Hz,1H),7.22(d,J=8.0Hz,2H),7.14(dd,J=16.2,2.1Hz,2H),6.27–6.08(m,1H),1.44–1.11(m,3H). 13 C NMR (101MHz, CDCl3) δ140.30 (s), 137.56 (d, J = 6.8Hz), 130.65 (s), 129.62 (s), 12 7.46(s),125.49(s),124.91(s),122.46(s),114.74(d,J=33.7Hz,1H),21.34(s).

[0114] Example 9

[0115]

[0116] (E)-1-bromo-2-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 66%). 19 FNMR (376MHz, CDCl3) δ-63.66 (dt, J = 8.0, 4.1Hz). 1 H NMR (400MHz, CDCl3) δ7.64(dd,J=8.0,0.9Hz,1H),7.61–7.49(m,2H),7.36(t,J=7.4Hz,1H),7.31–7.21(m,1H),6.19(dq,J=16.0,6.4Hz,1H). 13 C NMR(101MHz, CDCl3)δ136.61(q,J=7.0Hz),133.59(s),133.37(s),131.10(s,),1 27.81(s),127.58(s),124.68(s),124.50(s),121.82(s),118.56(q,J=34.1Hz).

[0117] Example 10

[0118]

[0119] (E)-1-bromo-3-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 71%). 19 FNMR (376MHz, CDCl3) δ-63.63 (dd, J=6.5, 2.1Hz). 1 H NMR (400MHz, CDCl3) δ7.63(d,J=1.6Hz,1H),7.53(d,J=8.0Hz,1H),7.38(t,J=8.6Hz,1H) ,7.29(dd,J=8.5,7.2Hz,1H),7.11(dq,J=16.1,2.0Hz,1H),6.23(dq,J=16.1,6.4Hz,1H). 13 C NMR (101MHz, CDCl3) δ136.24 (d, J = 6.8Hz), 135.47 (s), 132.90 (s), 130.44 (s), 130.3 3(s),126.19(s),124.59(s),123.05(s),122.16–121.37(m),117.36(d,J=34.1Hz).

[0120] Example 11

[0121]

[0122] (E)-1-bromo-4-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 76%). 19 FNMR (376MHz, CDCl3) δ-63.54 (dd, J=6.5, 2.1Hz). 1 H NMR (400MHz, CDCl3) δ7.59–7.51(m,2H),7.33(t,J=8.2Hz,2H),7.11(dd,J=16.2,2.1Hz,1H),6.30–6.15(m,1H). 13 C NMR (101MHz, CDCl3) δ 136.53 (q, J = 6.8Hz), 132.33 (s), 132.16 (s), 128.97 (s), 124.77 (s), 124.23 (s), 122.10 (s), 116.51 (q, J = 34.0Hz).

[0123] Example 12

[0124]

[0125] (E)-1-chloro-2-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 65%).19 FNMR (376MHz, CDCl3) δ-63.65 (dd, J=6.4, 2.1Hz). 1 H NMR (400MHz, CDCl3) δ7.62(d,J=2.2Hz,1H),7.60–7.54(m,2H),7.48–7.42(m,1H),7.38–7.31(m,1H),6.24(dq,J=16.1,6.4Hz,1H). 13 C NMR(101MHz, CDCl3)δ136.79(q,J=7.0Hz),133.59(s),133.37(s),131.10(s,),1 27.81(s),127.58(s),124.68(s),124.50(s),121.82(s),118.56(q,J=34.1Hz).

[0126] Example 13

[0127]

[0128] (E)-1-chloro-3-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 72%). 19 FNMR (376MHz, CDCl3) δ-63.63 (dd, J=6.4, 2.1Hz). 1 H NMR (400MHz, CDCl3) δ7.47 (s, 1H), 7.38 (ddd, J = 5.6, 4.3, 2.1Hz, 1H), 7.35 (d, J =5.0Hz,1H),7.12(ddd,J=16.1,4.2,2.1Hz,1H),6.24(dq,J=16.1,6.4Hz,1H). 13 CNMR(101MHz, CDCl3)δ136.34(d,J=6.8Hz),135.22(s),134.97–134.78(m),130.09(d,J=20.9 Hz),129.98(s),127.40(s),125.75(s),124.60(s),122.34–121.71(m),117.38(d,J=34.1Hz).

[0129] Example 14

[0130]

[0131] (E)-1-chloro-4-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 79%). 19F NMR (376MHz, CDCl3) δ-63.47 (dd, J=6.4, 2.1Hz). 1 H NMR (400MHz, CDCl3) δ7.38(t,J=9.2Hz,1H),7.29(s,1H),7.22(d,J=8.0Hz,1H),7.14(dd,J=16.2,2.1Hz,1H),6.27–6.10(m,1H). 13 C NMR (101MHz, CDCl3) δ140.30 (s), 137.56 (d, J = 6.8Hz), 130.65 (s), 129.62 (s), 127.46 (s), 125.68–124.90 (m), 122.46 (s), 114.74 (d, J = 33.7Hz).

[0132] Example 15

[0133]

[0134] (E)-1-nitro-3-(3,3,3-trifluoromethyl-1-propenyl)benzene, a yellow oily liquid (yield: 75%). 19 FNMR (376MHz, CDCl3) δ-63.92 (d, J=5.0Hz). 1 H NMR (400MHz, CDCl3) δ8.32(s,1H),8.23(d,J=8.0Hz,1H),7.78(d,J=7.7Hz,1H ),7.61(t,J=8.0Hz,1H),7.22(d,J=16.2Hz,1H),6.36(dq,J=15.8,6.2Hz,1H). 13 C NMR (101MHz, CDCl3) δ148.69 (s), 135.42 (q, J = 6.8Hz), 135.12 (s), 133.24 (s), 1 30.09 (s), 124.49 (s), 122.99 (q, J = 269.3Hz), 122.12 (s), 119.02 (q, J = 34.4Hz).

[0135] Example 16

[0136]

[0137] (E)-1,1,1-trifluoromethyl-2-tetrideene, colorless oily liquid (yield: 51%) 19 F NMR (376MHz, CDCl3) δ-63.9 (dd, J=6.3, 2.4Hz). 1H NMR (400MHz, CDCl3) δ6.43–6.30(m,1H),5.65–5.50(m,1H),2.19–2.07(m,2H),1.50–1.37(m,2H),1.36–1.18(m,14H),0.87(t,J=6.7Hz,3H). 13 C NMR (101MHz, CDCl3) δ 140.8 (q, J = 6.4Hz), 123.1 (q, J = 275.2Hz), 118.3 (q, J = 33.1Hz), 31.9 (s), 31.5 (s), 29.6 (s), 29.5 (s), 29.4 (s), 29.3 (s), 29.0 (s), 28.0 (q), 22.7 (s), 14.1 (s). Supplementary experiment:

[0138] Comparative Example 1

[0139]

[0140] Sodium trifluoromethyl sulfinate (1.2 mmol) and copper chloride (2.4 mmol) were reacted at 100 °C for 2 h in DCM (3 mL). The reaction was carried out using 4-methylstyrene (0.3 mmol) as a substrate, with a yield of 20%.

[0141] Comparative Example 2

[0142]

[0143] Sodium trifluoromethyl sulfinate (1.2 mmol), copper chloride (2.4 mmol) and sodium trifluoromethyl sulfinate (1.2 mmol) were reacted at 100 °C for 2 h in DCM (3 ml), and then DBU (0.6 mmol) was added and reacted at 80 °C for 2 h. After the reaction was completed, fluorine spectrum analysis showed that no product was formed.

[0144] The above yields are F-spectral yields, calibrated using trifluorotoluene as an internal standard.

Claims

1. A process for the preparation of a compound of formula II ###0001### II characterized in that, comprising the step of adding a compound represented by Formula I, CuX'2, CF3SO2Na, N(R 2 )4X in an ether solvent, and carrying out an addition reaction as shown below; ； X, X' and X" are independently halogen; R 1 is C1-C 15 alkyl, C6-C 10 aryl, 5-10 membered heteroaryl, C6-C 1-1 alkyl substituted by one or more R 10 aryl or 5-10 membered heteroaryl substituted by one or more R 1-2 ; the heteroatoms in said heteroaryl are selected from N, O and S, one or more, the number of heteroatoms being 1, 2, 3 or 4; R 1-1 and R 1-2 independently C1-C6alkyl, halogen or nitro; R 2 independently C1-C6alkyl; The temperature of the addition reaction is 50-120℃; The ether solvent is dioxane.

2. The process for the preparation of a compound of formula II as claimed in claim 1, wherein, One or more of the following conditions are met: (1) X, X' and X" are F, Cl, Br or I; (2) R 1 In particular, the C1-C 15 alkyl is C1-C 12 alkyl; (3) R 1 In particular, the C6-Ci8-aryl is phenyl or naphthyl. 10 In particular, the C6-Ci8-aryl is phenyl or naphthyl. (4) R 1 wherein the C6-C 1-1 substituted C6-C 10 aryl is phenyl or naphthyl; and 10 aryl is phenyl or naphthyl; and (5) R 1 In one embodiment, the 5-10 membered heteroaryl is or ; (6) R 1 In the above, the heteroaryl in the 5-10 membered heteroaryl group substituted by one or more R 1-2 In the above, the heteroaryl in the 5-10 membered heteroaryl group substituted by one or more R or ; (7) R 1-1 and R 1-2 wherein said C1-C6alkyl is C1-C4alkyl; (8) R 1-1 and R 1-2 wherein said halogen is F, Cl, Br or I; (9) R 2 In particular, the C1-C6alkyl group is a C1-C4alkyl group.

3. The method for preparing the compound represented by Formula II as described in claim 2, characterized in that, One or more of the following conditions are met: (1) X, X' and X" are Cl or Br; (2) R 1 In the context, C1-C 12 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, or n-decyl. (3) the 5-10 membered heteroaryl is or ; (4) the heteroaryl group in the substituted 5-10 membered heteroaryl group is 1-2 substituted with one or more R or ; (5) R 1-1 and R 1-2 wherein said C1-C4alkyl is methyl, ethyl, n-propyl, n-butyl, i-propyl or t-butyl; (6) R 2 In particular, the C1-C4alkyl group is methyl, ethyl, propyl or butyl.

4. The method for preparing the compound of formula II as described in claim 1, characterized in that, The compound of formula I is selected from any one of the following structures: 、 、 、 、 、 、 、 、 、 、 、 、 。 5. A process for the preparation of a compound of formula II according to any one of claims 1 to 4, characterized in that One or more of the following conditions are met: (1) X" in the compound of formula II is derived from X in the compound of formula (IV) or X' in the compound of formula (CuX'2); and 2 (2) X' in the compound of formula IV is derived from X in the compound of formula (IV) or X" in the compound of formula (CuX"2 (2) The addition reaction is carried out in the presence of oxygen; (3) The CuX'2 is one or more of cupric fluoride, copper chloride, copper bromide and copper iodide; (4) The molar concentration of the compound of formula I in the ether solvent is 0.01-1 mol / L; (5) The molar ratio of the compound of formula I to CF3SO2Na is 1:(1-4); (6) The molar ratio of the compound of formula I to CuX'2 is 1:(0.01-1); (7) The temperature of the addition reaction is 60-100℃.

6. The method for preparing the compound of formula II as described in claim 5, characterized in that, One or more of the following conditions are met: (1) The CuX'2 is copper bromide and / or copper chloride; (2) The molar ratio of the compound of formula I to CF3SO2Na is 1:(1-2); (3) The molar ratio of the compound of formula I to CuX'2 is 1:(0.05-0.5).

7. The method for preparing the compound of formula II as described in claim 5, characterized in that, All of the following conditions are met: (1) The CuX'2 is copper chloride; (2) The molar concentration of the compound of formula I in the ether solvent is 0.1 mol / L; (3) The molar ratio of the compound of formula I to CF3SO2Na is 1:1.1; (4) The molar ratio of the compound of formula I to CuX'2 is 1:0.11; (5) The molar ratio of CF3SO2Na to CuX'2 is 1:0.1; (6) The temperature of the addition reaction is 80℃.

8. A process for the preparation of a trifluoromethyl olefin, characterized in that, It comprises the following steps: (1) The addition reaction is carried out according to the preparation method of any one of claims 1-7 to obtain a compound of formula II; (2) The compound of formula II prepared in step (1) is subjected to an elimination reaction with a base in an organic solvent to obtain a compound of formula III; 。 9. The method for preparing trifluoromethyl olefin as described in claim 8, characterized in that, One or more of the following conditions are met: (1) After the reaction in step (1) is completed, the organic solvent is removed to proceed to step (2); (2) In step (2), the base is DBU; (3) In step (2), the organic solvent is a halogenated hydrocarbon solvent; (4) In step (2), the elimination reaction is carried out under closed conditions; (5) In step (2), the reaction temperature in the elimination reaction is 60-120 o C; (6) In step (2), the molar concentration of the compound of formula II in the organic solvent is 0.01-1 mol / L; (7) The molar ratio of the compound of formula I to the base in step (2) is 1:(1-3).

10. The method of claim 9, wherein the trifluoromethyl olefin is prepared by the process of: ###00016### 9 10 The molar ratio of the compound of formula I to the base in step (2) is 1:(1.5-2.5).

11. The method for preparing trifluoromethyl olefins according to claim 9, characterized in that, One or more of the following conditions are met: (1) In step (2), the organic solvent is dichloromethane; (2) In step (2), the elimination reaction is carried out in a sealed tube. (3) In step (2), the reaction temperature of the elimination reaction is 80 o C; (4) In step (2), the molar concentration of the compound of formula II in the organic solvent is 0.1 mol / L. (5) The molar ratio of the compound of formula I to the base in step (2) is 1:

2.

12. The process for the preparation of a trifluoromethyl olefin according to any one of claims 8 to 11, characterized in that, After the addition reaction in step (1) is completed, the organic solvent is removed to obtain a crude product, and the elimination reaction of the crude product and the base in the organic solvent is carried out.

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