Styryl bis (trifluoromethyl) methanol derivative and synthesis method thereof

Abstract

The invention discloses a styryl bis (trifluoromethyl) methanol derivative and a synthesis method thereof, the method takes benzoic acid bis (trifluoromethyl) iodine methanol ester, phenylacetylene and phenylboronic acid as raw materials, and the synthesis route is benzoyl chloride-IV-V-I, II and III. The synthesis method comprises the following steps: synthesizing an intermediate product benzoic acid bis (trifluoromethyl) chloromethanol ester (compound IV) by taking a common chemical raw material benzoyl chloride as a substrate, then synthesizing a precursor V (compound V) by using the compound IV, and finally synthesizing target products I, II and III by using the compound V. In the step, the compounds I, II, III and V are all brand new compounds. The invention provides a brand new thought for rapid synthesis of the styryl bis (trifluoromethyl) methanol derivative, and fills the blank of synthesis of the styryl bis (trifluoromethyl) methanol derivative. The method also has the advantages of simple operation, mild conditions, wide substrate application range and strong functional group tolerance.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic chemistry, and relates to a styryl bis(trifluoromethyl)methanol derivative and a synthesis method thereof. Background Art

[0002] Organic fluorine compounds have been widely used in the fields of medicine, pesticides, and functional materials. Compared with non-fluorine compounds, organic fluorine compounds can improve metabolic stability, lipophilicity, cell membrane permeability, etc. Many organic fluorine compounds have important uses. For example, levofloxacin is used as an antibacterial drug; polytetrafluoroethylene can be used as a component of artificial joints and is used in the human body for a long time. Inorganic fluorides are very abundant in the earth's reserves, but organic fluorine compounds are extremely rare in natural products and are mostly synthetically produced artificially. The unique physical and chemical properties of organic fluorine compounds have prompted researchers to continuously develop new organic fluorine compounds and new synthesis methods for organic fluorides. Considerable achievements have also been made in this research work.

[0003] Among many fluorine-containing groups, the bis(trifluoromethyl)methanol group is a type of potential pharmacophore. Bis(trifluoromethyl)methanol derivatives have received extensive attention in the field of organic synthesis due to their unique structures and biological activities. However, there are relatively few methods for introducing the bis(trifluoromethyl)methanol group into organic compounds. Existing methods for introducing the bis(trifluoromethyl)methanol group include: 1). Nucleophilic attack of trifluoromethyl anion on active carbonyl compounds. However, the synthesis steps of active carbonyl compounds are relatively cumbersome. For reference, see (Angewandte Chemie International Edition., 2018, 130, 1395-1399.) 2). Nucleophilic addition of metal reagents to hexafluoroacetone, but this method has poor functional group tolerance. For reference, see (Journal of the American Chemical Society., 2012, 134, 11185-11195.) 3). Electrophilic substitution (SEAr) type reaction of electron-rich aromatics, but this method is limited to electron-rich aromatic systems and the substrate scope of application is greatly restricted. For reference, see (The Journal of Organic Chemistry., 2022, 87, 9128-9138.) 4). Nucleophilic ring-opening reaction of 2,2-bis(trifluoromethyl)oxirane, but the types of products obtained by this method are relatively single. For reference, see (Journal of Fluorine Chemistry., 2011, 132, 41-51.) Currently, the synthesis of styryl bis(trifluoromethyl)methanol derivatives is still blank in research. Therefore, the effective synthesis of bis(trifluoromethyl)methanol derivatives remains a huge challenge in organic synthetic chemistry. Summary of the Invention

[0004] Based on the disadvantages existing in the above-mentioned prior art, the object of the present invention is to provide a styryl bis(trifluoromethyl)methanol derivative based on phenylacetylene and phenylboronic acid and its synthesis method. The present invention has developed a three-component radical cascade reaction among bis(trifluoromethyl)iodomethyl benzoate, phenylacetylene and phenylboronic acid, providing a brand-new idea for the rapid synthesis of styryl bis(trifluoromethyl)methanol derivatives.

[0005] One object of the present invention is to provide styryl bis(trifluoromethyl)methanol derivatives I, II, III, and their structural formulas are as follows:

[0006]

[0007] Another object of the present invention is to provide bis(trifluoromethyl)iodomethyl benzoate V, which is a precursor substance of styryl bis(trifluoromethyl)methanol derivatives I, II, III, and its structural formula is as follows:

[0008]

[0009] A third object of the present invention is to provide a synthesis method of a styryl bis(trifluoromethyl)methanol derivative. This method is based on bis(trifluoromethyl)iodomethyl benzoate (V), phenylacetylene and phenylboronic acid. Using compound V as a precursor, adding reactants phenylacetylene, phenylboronic acid / 3-chlorophenylboronic acid / 4-bromophenylboronic acid, adding a catalyst and a solvent, and stirring and reacting for a period of time in a basic environment to obtain compound I / II / III;

[0010] Among them, the corresponding products of the reactants phenylboronic acid / 3-chlorophenylboronic acid / 4-bromophenylboronic acid are compound I / II / III respectively. The specific synthesis route is as follows:

[0011] S1. Synthesize compound IV:

[0012]

[0013] S2. Synthesize compound V:

[0014]

[0015] S3. Synthesize styryl bis(trifluoromethyl)methanol derivatives I, II, III:

[0016]

[0017] Furthermore, the specific steps for synthesizing the above compounds I-V are as follows:

[0018] S1. Synthesize compound IV:

[0019] S1.1 Take benzoyl chloride and pyridine in a reaction vessel, stir at room temperature, introduce hexafluoroacetone gas, continue stirring, and monitor by TLC (Thin-Layer Chromatography).

[0020] S1.2 After the reaction is completed, add petroleum ether, silica gel, and pyridine, and stir at room temperature.

[0021] S1.3 After the reaction is completed, filter off the silica gel by suction filtration and concentrate to obtain the crude product bis(trifluoromethyl)chloromethanol benzoate IV.

[0022] Furthermore, in step S1.1, the molar ratio of benzoyl chloride, pyridine, and hexafluoroacetone is (0.8 - 1.2):(0.01 - 0.03):(2.8 - 3.2), preferably 1:0.02:3; the total stirring time is 10 - 24 h, preferably 12 h; the purpose of TLC monitoring is to monitor the reaction process. The specific operation method is as follows: After spotting on a silica gel plate, place it in a container containing the developing agent for development. After a period of time, dry it and develop the color, and analyze the results and the reaction process. The more specific operation method is a conventional operation in the art and is not a distinguishing technical feature of the present invention, so it will not be elaborated here. The same applies hereinafter. The developing agent is pure petroleum ether. The same applies hereinafter.

[0023] In step S1.2, the molar ratio of the added petroleum ether, silica gel, and pyridine to the molar amount of benzoyl chloride after the reaction is completed is (4 - 5):(0.08 - 0.12):(0.6 - 0.8):(0.8 - 1.2), preferably 4.6:0.1:0.7:1; the total stirring time is 1 - 3 h, preferably 1 h. In addition, in step S1.1, the role of pyridine is to provide a basic environment for the reaction. In step S1.2, the role of pyridine is to remove the unreacted benzoyl chloride. The role of petroleum ether is to act as a solvent to dilute the reaction solution. The role of silica gel is to remove the product of the reaction between benzoyl chloride and pyridine.

[0024] The suction filtration in step S1.3 is preferably carried out in a sintered glass funnel.

[0025] S2. Synthesize compound V:

[0026] S2.1 Take the bis(trifluoromethyl)chloromethanol benzoate IV prepared in step S1, place it together with tris(2-phenylpyridine)iridium and tetrabutylammonium iodide in a reaction vessel, add dichloromethane, irradiate the reaction system with a blue light lamp, stir at room temperature, and detect by TLC.

[0027] S2.2 After the reaction is completed, remove dichloromethane and purify by column chromatography to obtain bis(trifluoromethyl)iodomethanol benzoate V.

[0028] Further, in step S2.1, the molar ratio of bis(trifluoromethyl)chloromethanol benzoate IV, iridium tris(2-phenylpyridine), and tetrabutylammonium iodide is (0.8 - 1.2):(0.005 - 0.010):(4 - 6), preferably 1:0.008:5; the wavelength range of the blue light lamp is 400 - 500 nm, preferably 440 nm; the total stirring time is 8 - 24 h, preferably 12 h;

[0029] In step S2.2, the method for removing dichloromethane is concentration under reduced pressure, which is carried out in a rotary evaporator; the specific steps of column chromatography purification are column packing, sample loading, elution, collection, and concentration, which are conventional operations in the art and not the distinguishing technical features of the present invention, so they will not be elaborated here. The same applies hereinafter; among them, the eluent used in the elution step is petroleum ether:ethyl acetate = 50:1. In this step, dichloromethane is used as a solvent, iridium tris(2-phenylpyridine) is used as a catalyst, and tetrabutylammonium iodide is used as an iodine source to participate in the reaction.

[0030] S3. Synthesize compounds I, II, and III:

[0031] S3.1 Synthesize compound I:

[0032] In a reaction vessel, add compound V, as well as phenylacetylene, phenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane, and water, stir under an inert gas atmosphere, and monitor the reaction using a TLC plate; after the reaction is complete, dry the reaction solution to obtain an organic phase; concentrate the obtained organic phase and then purify and separate it by column chromatography to obtain the target product I as a yellow oily liquid;

[0033] Further, in step S3.1, the molar ratio of compound V, phenylacetylene, phenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane, and water is (0.8 - 1.2):(0.8 - 1.2):(3.5 - 4.5):(0.04 - 0.06):(12 - 18):(10 - 12), preferably 1:1:4:0.05:15:11; the stirring temperature is 20 - 80 °C, preferably 50 °C; the stirring time is 6 - 24 h, preferably 12 h; the drying of the reaction solution is preferably carried out using anhydrous sodium sulfate, anhydrous magnesium sulfate, or anhydrous calcium chloride. In this step, phenylacetylene and phenylboronic acid are used as reactants, the role of potassium carbonate is to provide an alkaline environment, the role of dichloromethane and water is to serve as reaction solvents, and the role of tetrakis(triphenylphosphine)palladium is to be a catalyst. The inert gas is preferably nitrogen.

[0034] S3.2 Synthesize compound II:

[0035] In a reaction vessel, compound V, phenylacetylene, 3-chlorophenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane and water are added. Stir under an inert gas atmosphere and monitor the reaction using a TLC plate. After the reaction is complete, dry the reaction solution to obtain an organic phase. Concentrate the obtained organic phase and purify it by column chromatography to obtain the yellow solid as the target product II.

[0036] Further, the molar ratio of compound V, phenylacetylene, 3-chlorophenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane and water in step S3.2 is (0.8 - 1.2):(0.8 - 1.2):(3.5 - 4.5):(0.04 - 0.06):(12 - 18):(10 - 12), preferably 1:1:4:0.05:15:11. The temperature of the stirring is 20 - 80°C, preferably 50°C. The time of the stirring is 6 - 24 h, preferably 12 h. The drying of the reaction solution is preferably carried out using anhydrous sodium sulfate, anhydrous magnesium sulfate or anhydrous calcium chloride. In step S3.2, phenylacetylene and 3-chlorophenylboronic acid are used as reactants. The role of potassium carbonate is to provide an alkaline environment. The role of dichloromethane and water is to serve as reaction solvents. The role of tetrakis(triphenylphosphine)palladium is to act as a catalyst. The inert gas is preferably nitrogen.

[0037] S3.3 Synthesis of compound III:

[0038] In a reaction vessel, compound V, phenylacetylene, 4-bromophenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane and water are added. Stir under an inert gas atmosphere and monitor the reaction using a TLC plate. After the reaction is complete, dry the reaction solution to obtain an organic phase. Concentrate the obtained organic phase and purify it by column chromatography to obtain the yellow solid as the target product III.

[0039] Further, the molar ratio of compound V, phenylacetylene, 4-bromophenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane and water in step S3.3 is (0.8 - 1.2):(0.8 - 1.2):(3.5 - 4.5):(0.04 - 0.06):(12 - 18):(10 - 12), preferably 1:1:4:0.05:15:11. The temperature of the stirring is 20 - 80°C, preferably 50°C. The time of the stirring is 6 - 24 h, preferably 12 h. The drying of the reaction solution is preferably carried out using anhydrous sodium sulfate, anhydrous magnesium sulfate or anhydrous calcium chloride. In step S3.2, phenylacetylene and 4-bromophenylboronic acid are used as reactants. The role of potassium carbonate is to provide an alkaline environment. The role of dichloromethane and water is to serve as reaction solvents. The role of tetrakis(triphenylphosphine)palladium is to act as a catalyst. The inert gas is preferably nitrogen.

[0040] A fourth object of the present invention is to provide an application of a styryl bis(trifluoromethyl)methanol derivative, in which the styryl bis(trifluoromethyl)methanol derivative is used to prepare pesticides, antibacterial agents, or used as a biocompatible functional material.

[0041] Compared with the prior art, the present invention has at least the following improvements and beneficial effects:

[0042] The present invention uses bis(trifluoromethyl)iodomethyl benzoate V as a bis(trifluoromethyl)methanolization reagent, and through a three-component radical cascade reaction between compound V, phenylacetylene and phenylboronic acid, styryl bis(trifluoromethyl)methanol derivatives can be specifically synthesized, filling the blank of the synthesis of styryl bis(trifluoromethyl)methanol derivatives. In addition, the prior art has problems such as limited substrate scope and poor functional group tolerance; the present invention has the advantages of simple operation, mild conditions, wide substrate scope, and strong functional group tolerance. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 It is a summary diagram of the structural formulas of compounds I, II, III, IV and V of the present invention;

[0044] Figure 2 It is a preparation flow chart of compound IV of the present invention;

[0045] Figure 3 It is a preparation flow chart of compound V of the present invention;

[0046] Figure 4 It is a preparation flow chart of compound I of the present invention;

[0047] Figure 5 It is a preparation flow chart of compound II of the present invention;

[0048] Figure 6 It is a preparation flow chart of compound III of the present invention;

[0049] Figure 7 It is the 1H NMR spectrum of IV of the present invention (CDCl3, 298K);

[0050] Figure 8 It is the 13C NMR spectrum of IV of the present invention (CDCl3, 298K);

[0051] Figure 9 It is the 19F NMR spectrum of IV of the present invention (CDCl3, 298K);

[0052] Figure 10 It is the 1H NMR spectrum of V of the present invention (CDCl3, 298K);

[0053] Figure 1113C NMR spectrum of V of the present invention (CDCl3, 298K);

[0054] Figure 12 19F NMR spectrum of V of the present invention (CDCl3, 298K);

[0055] Figure 13 1H NMR spectrum of I of the present invention (CDCl3, 298K);

[0056] Figure 14 13C NMR spectrum of I of the present invention (CDCl3, 298K);

[0057] Figure 15 19F NMR spectrum of I of the present invention (CDCl3, 298K);

[0058] Figure 16 1H NMR spectrum of II of the present invention (CDCl3, 298K);

[0059] Figure 17 13C NMR spectrum of II of the present invention (CDCl3, 298K);

[0060] Figure 18 19F NMR spectrum of II of the present invention (CDCl3, 298K);

[0061] Figure 19 1H NMR spectrum of III of the present invention (CDCl3, 298K);

[0062] Figure 20 13C NMR spectrum of III of the present invention (CDCl3, 298K);

[0063] Figure 21 19F NMR spectrum of III of the present invention (CDCl3, 298K). Detailed Description of the Invention

[0064] To enable those skilled in the art to better understand the technical solutions of the present invention, the present invention will be described in detail below with reference to specific embodiments. It should be noted that the following embodiments will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be pointed out that for those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made. These all fall within the protection scope of the present invention.

[0065] There are no particular restrictions on the sources of all raw materials of the present invention, and those purchased on the market or prepared by conventional methods well-known to those skilled in the art can be used.

[0066] Compounds I, II, III, and V in the present invention are all novel compounds, and their structural formulas are shown in Figure 1 .

[0067] Example 1: Preparation process of Compound IV.

[0068] The structural formula of Compound IV described in this example is as follows (summarized in Figure 1 ):

[0069]

[0070] The specific preparation steps (refer to Figure 2 ) are as follows: Take benzoyl chloride (5.8 mL, 50 mmol) and pyridine (0.8 mL, 1 mmol) in a 100 mL Schlenk flask, stir at room temperature, introduce hexafluoroacetone gas (3 equiv.), stir at room temperature for 12 h, and monitor by TLC. After the reaction is completed, add 30 ml of petroleum ether and 250 mg of silica gel with a mesh size of 100 - 200, and then add 3 ml of pyridine to remove the unreacted benzoyl chloride. Stir at room temperature for 1 - 3 h. Filter with a sintered glass funnel and concentrate under reduced pressure to obtain the crude product bis(trifluoromethyl)chloromethyl benzoate IV, with a yield of 70% - 80%.

[0071] The formula for calculating the yield is: actual yield / theoretical yield × 100%, the same hereinafter.

[0072] The proton nuclear magnetic resonance spectrum, carbon spectrum, and fluorine spectrum of Compound IV prepared in this example are shown in Figures 7 - 9 respectively. The peaks in the nuclear magnetic resonance spectrum match the corresponding peaks of chemical groups, indicating the successful preparation of Compound IV.

[0073] 1 H NMR (600 MHz, Chloroform - d) δ8.04 (d, J = 8.0 Hz, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H). 13 C NMR (151 MHz, Chloroform - d) δ160.21, 135.11, 130.63, 129.11, 127.39, 120.1 (q, J = 286.9 Hz), 89.25 (hept, J = 36.4 Hz). 19 F NMR (565 MHz, Chloroform - d) δ - 74.33.

[0074] Example 2: Preparation process of Compound V.

[0075] The structural formula of Compound V described in this example is as follows:

[0076]

[0077] Specific preparation steps (refer to Figure 3 ) are as follows: Take bis(trifluoromethyl)chloromethanol benzoate IV (3.06 g, 10 mmol) prepared in the previous step, tris(2-phenylpyridine)iridium (50 mg, 0.076 mmol), and tetrabutylammonium iodide (18.5 g, 50 mmol) in a 250 mL round-bottom flask, add 80 mL of dichloromethane, irradiate the reaction system with a 440 nm blue light lamp, stir at room temperature for 12 h, and detect by TLC. After the reaction is completed, concentrate under reduced pressure to remove dichloromethane, and purify by column chromatography (eluent: PE:EA = 50:1) to obtain bis(trifluoromethyl)iodomethanol benzoate V with a yield of 70%-85%.

[0078] The 1H NMR, 13C NMR, and 19F NMR spectra of compound V prepared in this example are as follows Figures 10 - 12 shown. The peaks in the NMR spectra match the corresponding peaks of the chemical groups, indicating the successful preparation of compound V.

[0079] 1 H NMR (400 MHz, Chloroform-d) δ 8.01 (dd, J = 8.3, 1.5 Hz, 2H), 7.67 (td, J = 7.3, 1.4 Hz, 1H), 7.50 (t, J = 7.9 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 161.34, 135.02, 130.49, 128.98, 127.69, 120.79 (q, J = 287 Hz), 57.52 (quasi-hept, J = 34.7 Hz). 19 19F NMR (376 MHz, Chloroform-d) δ -70.22.

[0080] Example 3: Preparation process of the target product I.

[0081] The structural formula of compound I described in this example is as follows:

[0082]

[0083] Specific preparation steps (refer to Figure 4)Procedure: In a 10 mL Schlenk tube, add compound V (0.040 g, 0.1 mmol), phenylacetylene (0.010 g, 0.1 mmol), phenylboronic acid (0.012 g, 0.1 mmol), potassium carbonate (0.055 g, 0.4 mmol), tetrakis(triphenylphosphine)palladium (0.006 g, 0.005 mmol), dichloromethane (1 mL) and water (0.2 mL). Under a nitrogen atmosphere, stir at 50 °C for 12 hours and monitor the reaction using a TLC plate. After the reaction is complete, dry the reaction solution with anhydrous sodium sulfate to obtain the organic phase. Concentrate the obtained organic phase and purify it by column chromatography (eluent: PE / EA = 50 / 1) to obtain the target product I as a yellow oily liquid with a yield of 73%.

[0084] The 1H NMR, 13C NMR, and 19F NMR spectra of compound I prepared in this example are as follows Figures 13 - 15 shown. The peaks in the NMR spectra match the peaks corresponding to the chemical groups, indicating the successful preparation of compound I.

[0085] 1 H NMR (400 MHz, Chloroform-d) δ 7.54 (d, J = 7.7 Hz, 2H), 7.47 (t, J = 7.5 Hz, 1H), 7.34–7.25 (m, 4H), 7.25–7.18 (m, 3H), 7.08 (d, J = 7.6 Hz, 2H), 6.89 (t, J = 7.6 Hz, 2H), 6.69 (t, J = 7.4 Hz, 1H), 6.10 (s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 161.54, 150.39, 142.49, 136.72, 133.57, 130.11, 129.52, 128.80, 128.43, 127.86, 127.83, 127.69, 127.65, 127.32, 122.02 (q, J = 290.7 Hz), 82.37 (quasi-hept, J = 30.3 Hz). 19 F NMR (376 MHz, Chloroform-d) δ -70.85.

[0086] Example 4: Preparation process of target product II.

[0087] The structural formula of compound II described in this example is as follows:

[0088]

[0089] Specific preparation steps (refer to Figure 5)Procedure: In a 10 mL Schlenk tube, add compound V (0.040 g, 0.1 mmol), phenylacetylene (0.010 g, 0.1 mmol), 3-chlorophenylboronic acid (0.016 g, 0.1 mmol), potassium carbonate (0.055 g, 0.4 mmol), tetrakis(triphenylphosphine)palladium (0.006 g, 0.005 mmol), dichloromethane (1 mL) and water (0.2 mL). Stir at 50 °C for 12 hours under a nitrogen atmosphere and monitor the reaction using a TLC plate. After the reaction is complete, dry the reaction solution with anhydrous sodium sulfate to obtain the organic phase. Concentrate the obtained organic phase and purify it by column chromatography (eluent: PE / EA = 50 / 1) to obtain the yellow solid as the target product II with a yield of 68%.

[0090] The 1H NMR, 13C NMR, and 19F NMR spectra of compound II prepared in this example are as follows Figures 16 - 18 shown. The peaks in the NMR spectra match the peaks corresponding to the chemical groups, indicating the successful preparation of compound II.

[0091] 1 H NMR (400 MHz, Chloroform-d) δ 7.56–7.51 (m, 2H), 7.47 (dd, J = 8.3, 6.7 Hz, 1H), 7.35–7.18 (m, 4H), 7.16 (d, J = 1.9 Hz, 1H), 7.12–7.03 (m, 3H), 6.90 (t, J = 7.7 Hz, 2H), 6.71 (t, J = 7.5 Hz, 1H), 6.08 (s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 161.52, 149.25, 144.28, 136.01, 134.47, 133.67, 130.11, 129.69, 129.44, 128.85, 127.90, 127.82, 127.63, 127.54, 126.05, 121.93 (q, J = 290.7 Hz), 113.01, 82.21 (quasi-hept, J = 30.2 Hz). 19 F NMR (376 MHz, Chloroform-d) δ -70.73.

[0092] Example 5: Preparation process of the target product III.

[0093] The structural formula of compound III described in this example is as follows:

[0094]

[0095] Specific preparation steps (reference Figure 6)Procedure: In a 10 mL Schlenk tube, add compound V (0.040 g, 0.1 mmol), phenylacetylene (0.010 g, 0.1 mmol), 4-bromophenylboronic acid (0.020 g, 0.1 mmol), potassium carbonate (0.055 g, 0.4 mmol), tetrakis(triphenylphosphine)palladium (0.006 g, 0.005 mmol), dichloromethane (1 mL) and water (0.2 mL) solution. Under a nitrogen atmosphere, stir at 50 °C for 12 hours and monitor the reaction using a TLC plate. After the reaction is complete, dry the reaction solution with anhydrous sodium sulfate to obtain the organic phase. Concentrate the obtained organic phase and purify it by column chromatography (eluent: PE / EA = 50 / 1) to obtain the yellow solid as the target product III with a yield of 63%.

[0096] The 1H NMR, 13C NMR, and 19F NMR spectra of compound III prepared in this example are as follows Figures 19 - 21 shown. The peaks in the NMR spectra match the corresponding chemical groups, indicating the successful preparation of compound IV.

[0097] 1 H NMR (400 MHz, Chloroform-d) δ 7.56–7.50 (m, 2H), 7.47 (t, J = 7.5 Hz, 1H), 7.43–7.37 (m, 2H), 7.25 (t, J = 7.8 Hz, 2H), 7.09–7.02 (m, 4H), 6.89 (t, J = 7.8 Hz, 2H), 6.70 (t, J = 7.5 Hz, 1H), 6.07 (s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 161.52, 149.38, 141.40, 136.18, 133.66, 131.60, 130.10, 129.48, 129.42, 127.89, 127.78, 127.56, 123.36, 121.84 (q, J = 275.2 Hz), 112.23, 82.26 (quasi-hept, J = 30.0 Hz). 19 F NMR (376 MHz, Chloroform-d) δ -70.77.

[0098] The above description of the embodiments is for the convenience of those of ordinary skill in the art to understand and use the invention. Those skilled in the art can obviously make various modifications to these embodiments easily and apply the general principles described herein to other embodiments without creative labor. Therefore, the present invention is not limited to the above embodiments, and the improvements and modifications made by those skilled in the art without departing from the scope of the present invention according to the disclosure of the present invention should be within the protection scope of the present invention.

Claims

1. A styryl bis(trifluoromethyl) methanol derivative, characterized in that, The styryl bis(trifluoromethyl) methanol derivatives are selected from Compound I, II or III, and the structural formulas of Compound I, II or III are shown as follows respectively:

2. Bis(trifluoromethyl)iodomethyl benzoate, characterized in that, It is Compound V. Compound V is the precursor of the styryl bis(trifluoromethyl) methanol derivative described in Claim 1, and the structural formula of Compound V is shown as follows:

3. A method for synthesizing a styryl bis(trifluoromethyl) methanol derivative as described in claim 1, characterized in that, The synthesis method is as follows: Using Compound V as the precursor, adding reactants phenylacetylene, phenylboronic acid / 3-chlorophenylboronic acid / 4-bromophenylboronic acid, adding a catalyst and a solvent, and stirring and reacting for a period of time under an alkaline environment to obtain Compound I / II / III; Among them, the corresponding products of the reactants phenylboronic acid / 3-chlorophenylboronic acid / 4-bromophenylboronic acid are Compound I / II / III respectively.

4. The synthesis method of a styryl bis(trifluoromethyl) methanol derivative according to claim 3, characterized in that, This method specifically includes the following steps: S1. Synthesize Compound IV: S1.1 Take benzoyl chloride and pyridine in a reaction vessel, stir at room temperature, introduce hexafluoroacetone gas, and continue stirring; S1.2 After the reaction ends, add petroleum ether, silica gel, and pyridine, and stir at room temperature; S1.3 After the reaction ends, filter off the silica gel by suction filtration and concentrate to obtain the crude product bis(trifluoromethyl) chloro methyl benzoate, that is, Compound IV; S2. Synthesize Compound V: S2.1 Take Compound IV prepared in Step S1, put it together with iridium tris(2-phenylpyridine) and tetrabutylammonium iodide in a reaction vessel, add dichloromethane, and stir at room temperature; S2.2 After the reaction ends, remove dichloromethane and purify to obtain bis(trifluoromethyl) iodo methyl benzoate, that is, Compound V; S3. Synthesize Compound I, II, III: S3.1 Synthesize Compound I: In a reaction vessel, add Compound V, as well as phenylacetylene, phenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine) palladium, dichloromethane and water, and stir under an inert gas atmosphere; after the reaction is complete, dry the reaction solution to obtain an organic phase; concentrate the obtained organic phase and then purify and separate to obtain Compound I; S3.2 Synthesize Compound II: In a reaction vessel, add Compound V, as well as phenylacetylene, 3-chlorophenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine) palladium, dichloromethane and water, and stir under an inert gas atmosphere; after the reaction is complete, dry the reaction solution to obtain an organic phase; concentrate the obtained organic phase and then purify and separate to obtain Compound II; S3.3 Synthesize Compound III: In a reaction vessel, add Compound V, as well as phenylacetylene, 4-bromophenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine) palladium, dichloromethane and water, and stir under an inert gas atmosphere; after the reaction is complete, dry the reaction solution to obtain an organic phase; concentrate the obtained organic phase and then purify and separate to obtain Compound III.

5. A method for synthesizing a styryl bis(trifluoromethyl) methanol derivative according to claim 4, characterized in that, In Step S1.1, the molar ratio of the benzoyl chloride, pyridine, and hexafluoroacetone is (0.8 - 1.2):(0.01 - 0.03):(2.8 - 3.2); the total stirring time is 10 - 24 h; In Step S1.2, the molar ratio of the petroleum ether, silica gel, and pyridine added to the molar amount of benzoyl chloride is (4 - 5):(0.08 - 0.12):(0.6 - 0.8):(0.8 - 1.2).

6. The synthesis method of a styryl bis(trifluoromethyl) methanol derivative according to claim 3, characterized in that, In step S2.1, the molar ratio of bis(trifluoromethyl)chloromethanol benzoate IV, tris(2-phenylpyridine)iridium, and tetrabutylammonium iodide is (0.8 - 1.2):(0.005 - 0.010):(4 - 6); the total stirring time is 8 - 24 h.

7. A method for synthesizing a styryl bis(trifluoromethyl) methanol derivative according to claim 4, characterized in that In step S3.1, the molar ratio of compound V, phenylacetylene, phenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane, and water is (0.8 - 1.2):(0.8 - 1.2):(3.5 - 4.5):(0.04 - 0.06):(12 - 18):(10 - 12).

8. A method for synthesizing a styryl bis(trifluoromethyl) methanol derivative according to claim 4, characterized in that, In step S3.2, the molar ratio of compound V, phenylacetylene, 3-chlorophenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane, and water is (0.8 - 1.2):(0.8 - 1.2):(3.5 - 4.5):(0.04 - 0.06):(12 - 18):(10 - 12).

9. A method for synthesizing a styryl bis(trifluoromethyl) methanol derivative according to claim 4, characterized in that, In step S3.3, the molar ratio of compound V, phenylacetylene, 4-bromophenylboronic acid, potassium carbonate, tetrakis(triphenylphosphine)palladium, dichloromethane, and water is (0.8 - 1.2):(0.8 - 1.2):(3.5 - 4.5):(0.04 - 0.06):(12 - 18):(10 - 12); In steps 3.1 - 3.3, the stirring temperature is 20 - 80 °C, and the stirring time is 6 - 24 h.

10. Application of a styryl bis(trifluoromethyl) methanol derivative, characterized in that, In the said application, styryl bis(trifluoromethyl)methanol derivatives are used to prepare pesticides, antibacterial agents, or used as biocompatible functional materials.

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