Trifluoromethylated pyrazolone compound, synthetic method and application

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a trifluoromethylated pyrazolone compound, a synthesis method and application. According to the preparation method, sodium trifluoromethanesulfinate and an acylhydrazone compound are used as raw materials, tetrabutyl ammonium hexafluorophosphate is used as an electrolyte, and the pyrazolone compound with a potential corrosion inhibition effect and a medical application prospect is synthesized at room temperature in a nitrogen atmosphere. Compared with a previously reported synthesis method, the method has the advantages of greenness, environmental protection, safety, high efficiency and energy conservation, the substrate application range is wide, the functional group compatibility is good, the raw materials are easy to obtain, and the operation is simple and convenient.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a trifluoromethylated pyrazolone compound, a synthesis method and an application thereof. Background Art

[0002] Pyrazolone derivatives have a wide range of applications due to their superior structural advantages and biological activities, and are one of the most important nitrogen-containing ring compounds. Among them, pyrazolone compounds can form an adsorption film by acting on iron atoms on the surface of carbon steel, slowing down the occurrence of corrosion reactions, and being used as a corrosion inhibitor. At the same time, it is also the core skeleton of a variety of bioactive molecules and drug molecules, and these skeleton structures have medicinal values such as antipyretic, analgesic, anti-inflammatory, antibacterial, antidepressant, etc., such as edaravone for the treatment of acute cerebral ischemia; celecoxib for relieving arthritis and acute pain, etc. However, currently, these methods generally have disadvantages such as the use of transition metals such as palladium, gold, silver and other catalysts, peroxides such as tert-butyl hydroperoxide and relatively high reaction temperatures. Here, we introduce trifluoromethyl through a green and sustainable electrochemical synthesis method to synthesize trifluoromethyl-containing pyrazolone derivatives. Summary of the Invention

[0003] In view of this, the present invention discloses and provides a trifluoromethylated pyrazolone compound, a synthesis method and an application thereof.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] The first object of the present invention is to provide a synthesis method of a trifluoromethylated pyrazolone compound, comprising the following steps:

[0006] Using (E)-N'-benzylidene-N-methylacryloyl hydrazide derivative and sodium trifluoromethanesulfinate as reaction raw materials, mixing the reaction raw materials, electrolyte and solvent, and passing an electric current in a nitrogen atmosphere for cyclization reaction, so that the electric current induces sodium trifluoromethanesulfinate to generate trifluoromethyl radicals, promoting the cyclization of sulfonyl hydrazide compounds to obtain the trifluoromethylated pyrazolone compound;

[0007] Its synthesis route is:

[0008]

[0009] The reaction is carried out in a reaction vessel provided with a cathode and an anode, the anode and the cathode are oppositely arranged, with a distance of 3-10 mm, and part or all of the cathode and the anode are placed in the reaction solution of the reaction system, and the area of the opposite surfaces of the anode and the cathode placed in the reaction solution is 64-100 mm 2 , optimally 100 mm 2 ; an electric current is applied between the cathode and the anode in the reaction system.

[0010] Such asFigure 1 As shown, the present invention uses (E)-N'-benzylidene-N-methylacryloyl hydrazide derivative and sodium trifluoromethanesulfinate as raw materials, tetrabutylammonium hexafluorophosphate as an electrolyte, and under a nitrogen atmosphere, an electric current is induced to generate trifluoromethyl radicals from sodium trifluoromethanesulfinate, promoting the cyclization of sulfonyl hydrazide compounds to obtain trifluoromethylated pyrazolone compounds.

[0011] It should be noted that the (E)-N'-benzylidene-N-methylacryloyl hydrazide derivative is a known compound, and its synthesis method is as follows:

[0012] The aldehyde and hydrazine are stirred in methanol at 60 °C for 1 - 2 hours, then rinsed with petroleum ether. Next, it is dissolved in 0.1 M dichloromethane, 1.5 equivalents of triethylamine are added at 0 °C, and then 1.2 equivalents of methacryloyl chloride are added, and the mixture is stirred overnight.

[0013] Preferably, the structure of the sulfonyl hydrazide is as shown in Formula 1;

[0014]

[0015] Among them, R 1 is phenyl, thienyl, N-methylpyrrolyl, furyl or substituted phenyl, and the substituents are methyl, cyano, trifluoromethyl, carboxyl, fluorine atom, chlorine atom, bromine atom, and the number of substituents is 1 or 2.

[0016] Preferably, the structure of the sodium trifluoromethanesulfinate is as shown in Formula 2:

[0017]

[0018] Preferably, the proportional relationship of the sulfonyl hydrazide, sodium trifluoromethanesulfinate, electrolyte, and solvent is: 0.1 mmol: 0.3 mmol: 0.2 mmol: 4 mL. The anode is a carbon sheet, the cathode is a nickel sheet, the reaction current is 4 mA, and the reaction time is 5 h.

[0019] It should be noted that regarding the influence of the solvent on the reaction, preferably, the solvent is one of dimethyl sulfoxide, acetonitrile, and a mixture of acetonitrile and water; among them, the best solvent is a mixture of acetonitrile and water with a volume ratio of 5:1.

[0020] Furthermore, the reaction electrolyte is one of tetrabutylammonium perchlorate, tetrabutylammonium acetate, tetrabutylammonium tetrafluoroborate, and tetrabutylammonium hexafluorophosphate; preferably tetrabutylammonium hexafluorophosphate.

[0021] Furthermore, the reaction anode material is graphite or platinum, preferably graphite material; the reaction cathode material is one of graphite, nickel, and platinum, preferably nickel material.

[0022] Further, the reaction current is 2 - 10 mA, and the optimal reaction current is 4 mA; the reaction time is 3 - 5 hours, and the optimal reaction time is 5 hours; the reaction temperature is 10 - 50 °C, and the optimal reaction temperature is 25 °C.

[0023] The second object of the present invention is to provide a trifluoromethylated pyrazolone compound prepared by the above synthesis method.

[0024] The third object of the present invention is the application of pyrazolone compounds in the preparation of corrosion inhibitors and the core skeletons of drug molecules.

[0025] It should be noted that 1 - phenyl - 3 - methyl - 5 - pyrazolone is also known as edaravone, which is mainly used in the medical field, such as treating cerebral infarction. Pyrazolone derivatives (such as ketoprofen, piroxicam, antipyrine) are still used clinically. In recent years, it has been found that grafting picrolonic acid (4 - nitro - 3 - methyl - p - nitrophenyl - 5 - pyrazolone) onto the surface of graphene can significantly improve its stability in salt water. 5 - amino - 1 - phenyl - 3 - methylpyrazolone can inhibit calcium carbonate deposition when compounded with zinc salts in a circulating cooling water system.

[0026] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0027] 1. High efficiency: The synthesis reaction time is short and the yield is high;

[0028] 2. Environmental protection: An electrochemical method is adopted, without the use of toxic and harmful oxidants, reducing environmental hazards;

[0029] 3. Easy to scale up: The reaction device is simple, the electrode material can be reused, and it is easy to realize industrial production;

[0030] 4. Mild conditions: The reaction conditions are mild, without harsh conditions such as high temperature and high pressure;

[0031] 5. Readily available raw materials: The raw materials used are easy to prepare and have low costs;

[0032] 6. Simple operation: The operation is simple and it is easy to realize laboratory and industrial production.

[0033] In summary, this method uses "electrons" as a clean reagent, without the need to additionally add any oxidants or reductants, with mild conditions, energy conservation and environmental protection, cheap and readily available raw materials, simple operation, safety and reliability, easy to scale up for preparation and a relatively high product yield. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] To more clearly illustrate the technical solutions in the embodiments of the present invention or in the prior art, the following will briefly introduce the accompanying drawings required for the description of the embodiments or the prior art. Obviously, the accompanying drawings in the following description are only the embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other accompanying drawings can also be obtained based on the provided accompanying drawings.

[0035] Figure 1 It is the synthesis mechanism diagram of the trifluoromethylated pyrazolone compounds of the present invention.

[0036] Figure 2 It is the hydrogen spectrum diagram (a), carbon spectrum diagram (b) and fluorine spectrum diagram (c) of the pyrazolone compound prepared in Example 2 of the present invention.

[0037] Figure 3 It is the hydrogen spectrum diagram (a), carbon spectrum diagram (b) and fluorine spectrum diagram (c) of the pyrazolone compound prepared in Example 6 of the present invention. Detailed implementation manners

[0038] The following will clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0039] The special term "embodiment" used here, any embodiment described as "exemplary" does not have to be construed as superior to or better than other embodiments. For the performance index tests in the embodiments of this application, unless otherwise specified, the conventional test methods in the art are adopted. It should be understood that the terms described in this application are only for describing specific embodiments and are not used to limit the content disclosed in this application.

[0040] Unless otherwise specified, the technical and scientific terms used herein have the same meanings as those generally understood by those of ordinary skill in the technical field to which this application belongs; the test methods and technical means not otherwise specifically noted in this application refer to the experimental methods and technical means commonly adopted by those of ordinary skill in the art.

[0041] To better illustrate the content of this application, numerous specific details are given in the following detailed embodiments. Those skilled in the art should understand that this application can also be implemented without some specific details. In the embodiments, some methods, means, instruments, equipment, etc. well-known to those skilled in the art are not described in detail in order to highlight the main idea of this application.

[0042] On the premise of no conflict, the technical features disclosed in the embodiments of this application can be combined arbitrarily, and the obtained technical solutions belong to the content disclosed in the embodiments of this application.

[0043] The present invention discloses a method for synthesizing trifluoromethylated pyrazolone compounds.

[0044] To better understand the present invention, the following embodiments are used to further elaborate the present invention specifically, but it should not be construed as a limitation of the present invention. For those skilled in the art, some non-essential improvements and adjustments made based on the above invention content are also considered to fall within the protection scope of the present invention.

[0045] Example 1

[0046]

[0047] Under a nitrogen atmosphere, into a 15 mL Schlenk reaction tube, (E)-N'-benzylidene-N-methylacryloyl-4-methylbenzenesulfonyl hydrazide 2 (34.2 mg, 0.1 mmol), sodium trifluoromethanesulfinate (47.4 mg, 0.3 mmol), tetrabutylammonium hexafluorophosphate (77.5 mg, 0.2 mmol), and acetonitrile and water (5:1) were added in sequence. The reaction flask was equipped with a graphite sheet as the anode and cathode. The reaction tube was maintained at room temperature of 25 °C and a constant current of 4 mA. The reaction process was detected by TLC plate; after the reaction was completed, the volatile components were removed under reduced pressure, and then separated by silica gel column chromatography (the eluent was petroleum ether (60 - 90 °C) / ethyl acetate, v / v = 10:1) to obtain the target product as a pale yellow oil (30.4 mg, yield 74%).

[0048] The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0049] Comparative Example 1

[0050] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that the reaction was carried out without power supply in an air atmosphere, and the reaction was stopped. After post-treatment, the target product was not obtained.

[0051] It shows that the reaction cannot proceed without power supply.

[0052] Comparative Example 2

[0053] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that in an air atmosphere, the reaction was stopped. After post-treatment, the target product was obtained (24.2 mg, yield 59%).

[0054] It shows that an air atmosphere is not conducive to the reaction.

[0055] Comparative Example 3

[0056] The reaction steps and operations are the same as those in Example 1. The difference from Example 1 is that: in an air atmosphere, the reaction solvent is replaced with dimethyl sulfoxide. The reaction was stopped, and the target product was not obtained after post-treatment.

[0057] It shows that replacing the solvent is not conducive to the reaction.

[0058] Comparative Example 4

[0059] The reaction steps and operations are the same as those in Example 1. The difference from Example 1 is that: in an air atmosphere, the reaction constant current is 8 mA. The reaction was stopped, and the target product (21.7 mg, yield 53%) was obtained after post-treatment.

[0060] It shows that reducing the reaction constant current is not conducive to the reaction.

[0061] Example 2

[0062]

[0063] The reaction steps and operations are the same as those in Example 1. The difference from Example 1 is that (E)-N-methylacryloyl-4-methyl-N'-(4-methylbenzylidene)benzenesulfonylhydrazide (35.6 mg, 0.1 mmol) is added to the reaction system. After post-treatment, the target product as a pale yellow liquid (26.3 mg, yield 62%) was obtained.

[0064] The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0065] Example 3

[0066]

[0067] The reaction steps and operations are the same as those in Example 1. The difference from Example 1 is that (E)-N'-(4-bromobenzylidene)-N-methylacryloyl-4-methylbenzenesulfonylhydrazide (42.1 mg, 0.1 mmol) is added to the reaction system. The reaction was stopped, and the target product as a pale yellow liquid (33.3 mg, yield 68%) was obtained after post-treatment.

[0068] The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0069] Example 4

[0070]

[0071] The reaction steps and operations were the same as in Example 1. The difference from Example 1 was that (E)-N'-(4-iodobenzylidene)-N-methacryloyl-4-methylbenzenesulfonylhydrazide (46.8 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product as a pale yellow liquid (33.2 mg, yield 62%) was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0072] Example 5

[0073]

[0074] The reaction steps and operations were the same as in Example 1. The difference from Example 1 was that (E)-N-methacryloyl-4-methyl-N'-(4-(trifluoromethyl)benzylidene)benzenesulfonylhydrazide (41.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product as a pale yellow liquid (28.2 mg, yield 59%) was obtained. The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0075] Example 6

[0076]

[0077] The reaction steps and operations were the same as in Example 1. The difference from Example 1 was that (E)-N'-benzylidene-N-phenylmethacryloylhydrazide (26.4 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product as a pale yellow liquid (140 mg, yield 42%) was obtained.

[0078] The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0079] Example 7

[0080]

[0081] The reaction steps and operations were the same as in Example 1. The difference from Example 1 was that (E)-N'-((1-methyl-1H-pyrrol-2-yl)methylene)-N-phenylmethacryloylhydrazide (26.7 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product as a pale yellow liquid (18.0 mg, yield 37%) was obtained.

[0082] The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0083] Example 8

[0084]

[0085] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that (E)-N-methylacryloyl-4-methyl-N'-(3,4,5-trimethoxybenzylidene)benzenesulfonylhydrazide (43.2 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product as a pale yellow liquid (22.5 mg, yield 45%) was obtained.

[0086] The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0087] Example 9

[0088]

[0089] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that (E)-N'-(3,4-dichlorobenzylidene)-N-methylacryloyl-4-methylbenzenesulfonylhydrazide (41.1 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product as a pale yellow liquid (21.9 mg, yield 46%) was obtained.

[0090] The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0091] Example 10

[0092]

[0093] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that (E)-N'-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)-N-methylacryloyl-4-methylbenzenesulfonylhydrazide (40.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product as a white solid (25.3 mg, yield 54%) was obtained.

[0094] The target product was confirmed by nuclear magnetic resonance spectroscopy.

[0095] Example 11

[0096]

[0097] The reaction steps and operations were the same as those in Example 1. The difference from Example 1 was that (E)-N'-(4-cyanobenzylidene)-N-methylacryloyl-4-methylbenzenesulfonylhydrazide (36.7 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped, and after post-treatment, the target product as a pale yellow oil (17.4 mg, yield 40%) was obtained.

[0098] The target product was confirmed by nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.

[0099] Example 12

[0100]

[0101] The reaction steps and operations were the same as those in Example 1, except that (E)-methyl 4-((2-methacryloyl-2-toluenesulfonylhydrazide)methyl)benzoate (40.0 mg, 0.1 mmol) was added to the reaction system. The reaction was stopped and the target product (36.0 mg, 77% yield) was obtained as a light yellow oil after post-treatment.

[0102] The target product was confirmed by NMR and high-resolution mass spectrometry.

[0103] Example 13

[0104] The reaction steps and operations were the same as those in Example 1, except that tetrabutylammonium acetate was added during the reaction. The reaction was stopped and the target product (16.1 mg, yield 39%) was obtained after treatment.

[0105] The target product was confirmed by NMR and high-resolution mass spectrometry.

[0106] Embodiment 14

[0107] The reaction steps and operations are the same as those of Example 1, except that tetrabutylammonium tetrafluoroborate is added during the reaction. The reaction is stopped and the target product (18.5 mg, yield 45%) is obtained through post-treatment.

[0108] The target product was confirmed by NMR and high-resolution mass spectrometry.

[0109] The characterization data of the above compounds are as follows:

[0110] 1) 4-methyl-5-(p-tolyl)-2-toluenesulfonyl-4-(2,2,2-trifluoroethyl)-2,4-dihydro-3H-pyrazol-3-one: pale yellow oil.

[0111] The NMR data of the pyrazolone compound prepared in Example 2 are as follows:

[0112] 1 H NMR (600MHz, CDCl3) δ7.96(d,J=8.4Hz,2H),7.65(d,J=8.4Hz,2H),7.33(d,J=8.4Hz, 2H),7.23(d,J=8.4Hz,2H),2.86-2.78(m,2H),2.42(s,3H),2.38(s,3H),1.54(s,3H).

[0113] 1313C NMR (150 MHz, CDCl3) δ 173.9, 160.1, 145.9, 142.0, 134.1, 129.9, 129.8, 128.4, 126.7, 124.2 (q, J = 276.0 Hz), 49.6 (d, J = 1.5 Hz), 40.3, (q, J = 28.5 Hz), 23.8, 21.9, 21.6.

[0114] 19 19F NMR (565 MHz, CDCl3) δ 14.6 (s).

[0115] C 20 H 19 HRMS calculated for F3N2O3S [M+Na] + : 447.0961; found: 447.0953.

[0116] 2) 4-Methyl-2-tosyl-4-(2,2,2-trifluoroethyl)-5-(4-(trifluoromethyl)phenyl)-2,4-dihydro-3H-pyrazol-3-one: pale yellow oil.

[0117] The NMR data of the pyrazolone compound prepared in Example 5 are as follows:

[0118] 1 1H NMR (600 MHz, CDCl3) δ 7.97 (d, J = 8.4 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 2.91 - 2.78 (m, 2H), 2.44 (s, 3H), 1.58 (s, 3H).

[0119] 13 13C NMR (150 MHz, CDCl3) δ 173.4, 158.7, 146.3, 133.9, 133.1, 132.8, 130.1, 128.4, 127.1, 126.1 (q, J = 4.5 Hz), 124.1 (q, J = 276.0 Hz), 123.7 (q, J = 270.0 Hz), 49.5 (d, J = 3.0 Hz), 40.3 (q, J = 30.0 Hz), 23.5, 21.9.

[0120] 19 19F NMR (565 MHz, CDCl3) δ 14.7 (s), 14.5 (s).

[0121] C 20 H 16 HRMS calculated for F6N2O3S [M+Na]+ : 501.0678; Found: 501.0668.

[0122] 3) 4-Methyl-2,5-diphenyl-4-(2,2,2-trifluoroethyl)-2,4-dihydro-3H-pyrazol-3-one: A pale yellow oil.

[0123] The NMR data of the pyrazolone compound prepared in Example 6 are as follows:

[0124] 1 H NMR (600 MHz, CDCl3) δ 8.02 (d, J = 7.8 Hz, 2H), 7.88 - 7.84 (m, 2H), 7.47 - 7.44 (m, 5H), 7.25 (t, J = 7.8 Hz, 1H), 3.07 - 2.99 (m, 1H), 2.97 - 2.89 (m, 1H), 1.65 (s, 3H).

[0125] 13 C NMR (150 MHz, CDCl3) δ 174.5, 159.0, 138.0, 130.7, 129.1 (d, J = 3.0 Hz), 126.4, 125.8, 124.7 (q, J = 276.0 Hz), 119.4, 49.7 (d, J = 3.0 Hz), 40.8 (q, J = 28.5 Hz), 23.9.

[0126] 19 F NMR (565 MHz, CDCl3) δ 14.5 (s).

[0127] C 18 H 14 The theoretical value of HRMS for C6H6F6N2O4S [M + Na] + : 355.1029; Measured value: 355.1027.

[0128] 4) 4-Methyl-5-(1-methyl-3-(trifluoromethyl)-1H-pyrrol-2-yl)-2-toluenesulfonyl-4-(2,2,2-trifluoroethyl)-2,4-dihydro-3H-pyrazol-3-one: A yellow oil.

[0129] The NMR data of the pyrazolone compound prepared in Example 7 are as follows:

[0130] 11H NMR (600 MHz, CDCl3) δ 7.93 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 4.2 Hz, 1H), 6.43 (d, J = 4.2 Hz, 1H), 3.93 (m, 3H), 2.80 - 2.74 (m, 1H), 2.70 - 2.64 (m, 1H), 2.45 (s, 3H), 1.55 (s, 3H).

[0131] 13 13C NMR (150 MHz, CDCl3) δ 172.5, 154.0, 146.3, 134.0, 130.0, 128.4, 126.9 (q, J = 26.5 Hz), 124.2 (q, J = 277.5 Hz), 120.8 (q, J = 265.5 Hz), 112.1, 111.4 (q, J = 4.5 Hz), 50.2 (d, J = 3.0 Hz), 40.4 (q, J = 28.5 Hz), 35.2 (d, J = 1.5 Hz), 24.2, 21.9.

[0132] 19 19F NMR (565 MHz, CDCl3) δ 18.4 (s), 14.6 (s).

[0133] C 19 H 17 HRMS calculated for C6H2F6N2O3S [M+Na]: + 504.0787; found: 504.0787.

[0134] 5) 5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-4-methyl-2-tolyl-4-(2,2,2-trifluoroethyl)-2,4-dihydro-3H-pyrazol-3-one: white solid. Melting point: 162.3 - 163.0 °C.

[0135] The NMR data of the pyrazolone compounds prepared in Example 10 are as follows:

[0136] 1 1H NMR (600 MHz, CDCl3) δ 7.95 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.28 - 7.24 (m, 2H), 6.89 (d, J = 8.4 Hz, 1H), 4.31 - 4.27 (m, 4H), 2.84 - 2.75 (m, 2H), 2.43 (s, 3H), 1.53 (s, 3H).

[0137] 1313C NMR (150 MHz, CDCl3) δ 173.9, 159.6, 146.5, 145.9, 143.8, 134.12, 129.9, 128.3, 124.2 (q, J = 276.0 Hz), 123.1, 120.4, 117.9, 115.9, 64.7, 64.3, 49.5 (d, J = 1.5 Hz), 40.3 (q, J = 28.5 Hz), 23.8, 21.9.

[0138] 19 19F NMR (565 MHz, CDCl3) δ 14.6 (s).

[0139] C 21 H 19 HRMS calculated value of F3N2O5S [M+Na] + : 491.0859; measured value: 491.0866.

[0140] 6) Methyl 4-(4-methyl-5-oxo-1-tosyl-4-(2,2,2-trifluoroethyl)-4,5-dihydro-1H-pyrazol-3-yl)benzoate: pale yellow oil.

[0141] The NMR data of the pyrazolone compound prepared in Example 12 are as follows:

[0142] 1 1H NMR (600 MHz, CDCl3) δ 8.08 (d, J = 8.4 Hz, 2H), 7.96 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H), 2.89 - 2.80 (m, 2H), 2.42 (s, 3H), 1.57 (s, 3H).

[0143] 13 13C NMR (150 MHz, CDCl3) δ 173.5, 166.2, 159.1, 146.2, 133.9, 133.6, 132.4, 130.2, 130.0, 128.3, 126.7, 124.1 (q, J = 277.5 Hz), 52.5, 49.5 (d, J = 1.5 Hz), 40.2 (q, J = 30.0 Hz), 23.5, 21.8.

[0144] 19 19F NMR (565 MHz, CDCl3) δ 14.5 (s).

[0145] HRMS (ESI) m / z Calcd for C 21 H21 F3N2O5S HRMS theoretical value [M+Na] + : 491.0859; measured value: 491.0848.

[0146] II. Yield test

[0147] The present invention obtains the optimal reaction conditions by exploring reaction parameters and conducts a universality exploration under the optimal reaction conditions.

[0148] Table 1 Actual yield results of synthesizing pyrazolone compounds in Comparative Examples 1-4 and Examples 1-14

[0149] Specific Embodiment Yield Comparative Example 1 Failed to obtain the target product Comparative Example 2 59％ Comparative Example 3 Failed to obtain the target product Comparative Example 4 53％ Example 1 74％ Example 2 62％ Example 3 68％ Example 4 62％ Example 5 59％ Example 6 42％ Example 7 37％ Example 8 45％ Example 9 46％ Example 10 54％ Example 11 40％ Example 12 77％ Example 13 39％ Example 14 45％

[0150] Table 1 shows the actual yield results of synthesizing pyrazolone compounds in Examples 1-14 and Comparative Examples 1-4. It can be seen from Table 1 that compared with Example 1, the reaction in Comparative Example 1 was carried out without electricity. When the reaction was stopped, the target product was not obtained after post-treatment; this shows that the reaction cannot proceed without electricity. The reaction in Comparative Example 3 used dimethyl sulfoxide as the solvent. When the reaction was stopped, the target product was not obtained after post-treatment; this shows that the reaction cannot proceed in this solvent.

[0151] The present invention has expanded the scope of reaction substrates. As shown in Examples 1-12, pyrazolone compounds with trifluoromethylation can be prepared with good yields.

[0152] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be obvious to those skilled in the art. The general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A trifluoromethylated pyrazolone compound, characterized in that, The structure of the trifluoromethylated pyrazolone compounds is as follows: Among them, R 1 is phenyl, thienyl, N-methylpyrrolyl, furyl or substituted phenyl, the substituent is selected from methyl, cyano, trifluoromethyl, carboxyl, fluorine atom, chlorine atom, bromine atom, and the number of substituents is 1 or 2; R 2 is a tosyl group or a phenyl group.

2. A method for synthesizing the trifluoromethylated pyrazolone compounds as claimed in claim 1, characterized in that R 1 and R 2 are defined as in claim 1.

3. The synthesis method of the trifluoromethylated pyrazolone compounds according to claim 2, characterized in that, using (E)-N'-benzylidene-N-methylacryloyl hydrazide derivatives as raw materials, under electrochemical conditions, adding one equivalent of (E)-N'-benzylidene-N-methylacryloyl hydrazide derivatives, two equivalents of electrolyte and three equivalents of sodium trifluoromethanesulfinate for reaction to form the trifluoromethylated pyrazolone compounds.

4. The method for synthesizing trifluoromethylated pyrazolone compounds according to claim 2 or 3, characterized in that, In the electrochemical reaction, the reaction anode material is a carbon sheet, the reaction cathode material is one of graphite, nickel, and platinum, the reaction solvent is one of dimethyl sulfoxide, acetonitrile, and a mixture of acetonitrile and water (v:v = 5:1), the reaction electrolyte is one of tetrabutylammonium perchlorate, tetrabutylammonium acetate, tetrabutylammonium tetrafluoroborate, and tetrabutylammonium hexafluorophosphate, and the electrolyte concentration is 0.025 mol / L - 0.05 mol / L.

5. The method for synthesizing trifluoromethylated pyrazolone compounds according to claim 2 or 3, characterized in that, The constant current of the electrochemical reaction is 2 - 10 mA, the reaction time is 3 - 5 hours, the reaction temperature is 10 - 50 °C, and the reaction atmosphere is a nitrogen atmosphere; after the reaction is completed, the product is separated and purified by column chromatography to obtain the trifluoromethylated pyrazolone compounds.

6. An application of the trifluoromethylated pyrazolone compounds as claimed in claim 1 or the trifluoromethylated pyrazolone compounds prepared by the method as claimed in claim 2 in the preparation of corrosion inhibitors and the core skeletons of drug molecules.

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