A method for synthesizing beta-trifluoromethylthio ketone derivatives by ring-opening of cyclopropanol derivatives

Abstract

The application relates to the field of organic synthesis, in particular to a method for synthesizing beta-trifluoromethylsulfinyl ketone derivatives by ring-opening of cyclopropanol. 3 C intermediates, and then adding a trifluoromethylating agent S-trifluoromethyl-4-methylthiobenzenesulfonate to obtain beta-trifluoromethylsulfinyl ketone derivatives. The application uses the simple, easy-to-prepare and stable S-trifluoromethyl-4-methylthiobenzenesulfonate as a trifluoromethylating agent, and the reaction condition is mild, and the synthesis method is simple and easy to operate.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and specifically relates to a method for synthesizing β-trifluoromethylthioketone derivatives from cyclopropanol derivatives by ring-opening. Background Technology

[0002] Over the past decade, fluorine-containing organic molecules have demonstrated exceptional importance not only in the pesticide industry and materials science but also in medicinal chemistry. Trifluoromethyl (CF3) and trifluoromethylthio (SCF3), due to their unique physical and chemical properties, exhibit excellent lipophilicity, which helps adjust cell membrane permeability to improve bioavailability, and they are frequently found in life-saving drug molecules and agrochemicals. Given the importance of this component, organic researchers have developed numerous strategies to introduce trifluoromethylthio groups into small organic molecules. However, a large portion of the methods for introducing trifluoromethylthio groups involve constructing CS bonds between aromatics, alkenes, and trifluoromethylthio groups. Most current methods for constructing sp3C-SCF3 bonds rely on expensive, difficult-to-prepare, poorly reactive, and unstable trifluoromethylthioating reagents, or complex post-processing systems. Therefore, using inexpensive and readily available trifluoromethylthioating reagents to construct sp3C-SCF3 bonds through simple catalytic reactions is crucial. 3 The C-SCF3 bond is one of the hot research topics.

[0003] Meanwhile, the chemical properties of ring-opening reactions, especially those involving three-membered rings, have been extensively studied. Cyclopropanol, due to its inherent ring strain, is widely used as a starting material for various transition metal-mediated or catalytic ring-opening cross-coupling reactions. Moreover, cyclopropanol is a readily available three-membered ring and has found wide applications in organic synthesis and many natural products.

[0004] In 2015, Dai Mingji's research group achieved for the first time a copper-catalyzed ring-opening reaction of cyclopropanol derivatives with electrophilic trifluoromethyl and trifluoromethylthio groups, completing the construction of C-CF3 and C-SCF3 bonds via a radical mechanism. In 2017, Lopp's research group reported the cyclopropanol ring cleavage reaction of cyclopropanol derivatives in methanol with an oxidant in the presence of copper(II) acetate catalyst and sodium sulfinate, yielding derivatives of β-trifluoromethyl ketones.

[0005]

[0006] This patent describes a method for synthesizing β-trifluoromethylthioketones using S-trifluoromethyl-4-methylbenzenesulfonate as a trifluoromethylthiolation reagent via ring-opening of cyclopropanol. Under copper ligand catalysis, the cyclopropanol derivative undergoes ring-opening to form an sp3C intermediate, which is then reacted with the trifluoromethylthiolation reagent to yield β-trifluoromethylthioketone derivatives. Since S-trifluoromethyl-4-methylbenzenesulfonate can be easily prepared from p-toluidine and p-toluenesulfonyl chloride, the method used in this patent employs mild conditions, readily available substrates, and enables rapid synthesis of β-trifluoromethylthioketone derivatives. Summary of the Invention

[0007] To address the shortcomings of existing technologies, the present invention aims to provide a method for ring-opening synthesis of β-trifluoromethylthioketone derivatives from cyclopropanol derivatives.

[0008]

[0009] The objective of this invention is achieved through the following technical solution.

[0010] A method for preparing a β-trifluoromethylthioketone derivative, comprising the following steps:

[0011] Under anhydrous and oxygen-free conditions, a catalyst, oxidant, cyclopropanol reactants, S-trifluoromethyl-4-methylbenzenesulfonate, and solvent were mixed in a sealed container and stirred at 40°C for 12 hours to obtain β-trifluoromethyl thioether ketone derivatives. The molar ratio of the cyclopropanol derivative to S-trifluoromethyl-4-methylbenzenesulfonate was 1:1.8. The catalyst was anhydrous copper acetate, the oxidant was 2-iodobenzoic acid (IBX), and the solvent was acetonitrile. The general structural formula of the substituted cyclopropanol reactants is:

[0012]

[0013] Wherein, R1 is phenyl, p-methylphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, biphenyl, m-chlorophenyl, o-methoxyphenyl, benzyl, thiophenyl, furanyl, naphthyl, indoleyl, or benzothiophenyl.

[0014] In the above technical solution, the molar ratio of the catalyst to the cyclopropanol reactants is 3:10.

[0015] In the above technical solution, the molar ratio of the oxidant to the cyclopropanol reactant is 3:10.

[0016] In the above technical solution, the concentration of the cyclopropanol reactant in the solvent is 0.15 mol / L.

[0017] A β-trifluoromethylthioketone derivative obtained by the above preparation method, wherein the general structural formula of the β-trifluoromethylthioketone derivative is:

[0018]

[0019] Wherein, R1 is phenyl, p-methylphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, biphenyl, m-chlorophenyl, o-methoxyphenyl, benzyl, thiophenyl, furanyl, naphthyl, indoleyl, or benzothiophenyl.

[0020] The β-trifluoromethylthioketone derivatives synthesized by this invention are shown in the table below:

[0021]

[0022]

[0023]

[0024] Compared with existing technologies, the beneficial effects of the preparation method of the present invention are as follows:

[0025] 1. The reaction conditions in this experiment are mild, the raw materials and catalysts are inexpensive and readily available, and the substrates have a wide range of applicability;

[0026] 2. S-trifluoromethyl-4-methylphenylthiosulfonate is stable and easy to prepare;

[0027] 3. It can rapidly and efficiently synthesize β-trifluoromethylthioketone derivatives with different substitutions. Attached Figure Description

[0028] Figure 1 The image shows the H spectrum of the compound from Example 1.

[0029] Figure 2 The 1H spectrum is for the compound in Example 2.

[0030] Figure 3 The 1H spectrum is for the compound in Example 3.

[0031] Figure 4 The 1H spectrum is for the compound in Example 4.

[0032] Figure 5 The HCl spectrum is shown for the compound in Example 5.

[0033] Figure 6 The HCl spectrum is shown for the compound in Example 6.

[0034] Figure 7 The 1H spectrum is for the compound in Example 7.

[0035] Figure 8The 1H spectrum is of the compound in Example 8.

[0036] Figure 9 The 1H spectrum is for the compound in Example 9.

[0037] Figure 10 The 1H spectrum is of the compound in Example 10.

[0038] Figure 11 The 1H spectrum is of the compound in Example 11.

[0039] Figure 12 The H spectrum of the compound in Example 12 is shown.

[0040] Figure 13 The H spectrum of the compound in Example 13 is shown.

[0041] Figure 14 The H spectrum of the compound in Example 14 is shown.

[0042] Figure 15 The H spectrum of the compound in Example 15. Detailed Implementation

[0043] The method for synthesizing β-trifluoromethylthioketone derivatives from a cyclopropanol derivative provided by this invention, and the reaction formula thereof, are shown below:

[0044]

[0045] The operation steps are as follows:

[0046] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and a cyclopropanol derivative (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate) to obtain the product.

[0047] The following examples illustrate this point:

[0048] Example 1

[0049]

[0050] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-phenylcyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (46.6 mg, yield: 66%).

[0051] NMR data: 1 H NMR (400MHz, CDCl3): δ7.96 (d, J=8.0Hz, 2H), 7.60 (t, J=8.0Hz, 1H), 7.49 (t, J=8.0Hz, 2H), 3.44 (t, J=6.8Hz, 2H), 3.26 (t, J=6.8Hz, 2H); 13 C NMR (100MHz, CDCl3): δ196.95, 136.07, 133.63, 131.23 (q, J=304.0Hz, 1C), 128.75, 127.97, 38.89, 23.85; 19 F NMR (375MHz, CDCl3): δ -41.54.

[0052] Example 2:

[0053]

[0054] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(p-tolyl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (53.5 mg, yield: 72%).

[0055] NMR data: 1H NMR (400MHz, CDCl3): δ7.85 (d, J=8.0Hz, 2H), 7.28 (d, J=8.0Hz, 2H), 3.40 (t, J=6.8Hz, 2H), 3.25 (t, J=6.8Hz, 2H), 2.42 (s, 3H); 13 C NMR (100MHz, CDCl3): δ196.56, 144.54, 133.71, 131.28 (q, J=304.0Hz, 1C), 129.42, 128.10, 38.74, 23.97, 21.66; 19 F NMR (375MHz, CDCl3): δ-41.54.

[0056] Example 3:

[0057]

[0058] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(p-fluorophenyl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (43.1 mg, yield: 57%).

[0059] NMR data: 1 H NMR (400MHz, CDCl3): δ7.99 (q, J=4.0Hz, 2H), 7.15 (t, J=8.0Hz, 2H), 3.41 (t, J=6.8Hz, 2H), 3.25 (t, J=6.8Hz, 2H); 13 C NMR (100MHz, CDCl3): δ195.32, 167.30, 164.76, 131.21 (q, J = 304.0Hz, 1C), 130.66 (d, J = 10.0Hz, 1C), 115.90 (d, J = 21.9Hz, 1C), 38.84, 23.81; 19 F NMR (375MHz, CDC13): δ-41.54, -104.07.

[0060] Example 4:

[0061]

[0062] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(p-chlorophenyl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a bright yellow oily product (58.9 mg, yield: 73%).

[0063] NMR data: 1 H NMR (400MHz, CDCl3): δ7.89 (d, J=8.0Hz, 2H), 7.46 (d, J=8.0Hz, 2H), 3.40 (t, J=6.8Hz, 2H), 3.25 (t, J=6.8Hz, 2H); 13 C NMR (100MHz, CDCl3): δ195.71, 140.12, 134.35, 131.16 (q, J = 304.0Hz, 1C), 129.35, 129.06, 38.88, 23.71; 19 F NMR (375MHz, CDCl3): δ-41.52.

[0064] Example 5:

[0065]

[0066] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(p-bromophenyl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (61.7 mg, yield: 66%).

[0067] NMR data: 1 H NMR (400MHz, CDCl3): δ7.82 (d, J=8.0Hz, 2H), 7.63 (d, J=8.0Hz, 2H), 3.40 (t, J=6.8Hz, 2H), 3.25 (t, J=6.8Hz, 2H); 13C NMR (100MHz, CDCl3): δ195.94, 134.77, 132.09, 131.17 (q, J = 304.0Hz, 1C) 129.45, 128.89, 38.89, 23.72; 19 F NMR (375MHz, CDCl3): δ-41.50.

[0068] Example 6:

[0069]

[0070] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(p-methoxyphenyl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (56.8 mg, yield: 72%).

[0071] NMR data: 1 H NMR (400MHz, CDCl3): δ7.94 (d, J=8.0Hz, 2H), 6.95 (d, J=8.0Hz, 2H), 3.89 (s, 3H), 3.38 (t, J=6.8Hz, 2H), 3.25 (t, J=6.8Hz, 2H); 13 C NMR (100MHz, CDCl3): δ195.41, 163.85, 131.26 (q, J=304.0Hz, 1C), 130.26, 129.16, 113.85, 55.49, 38.43, 24.0; 19 F NMR (375MHz, CDCl3): δ -41.54.

[0072] Example 7:

[0073]

[0074] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-([1,1′-biphenyl]-4-yl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (69.0 mg, yield: 74%).

[0075] NMR data: 1 H NMR (400MHz, CDCl3): δ8.03 (d, J=8.0Hz, 2H), 7.71 (d, J=8.0Hz, 2H), 7.63 (d, J =7.2Hz, 2H), 7.49 (t, J = 7.0Hz, 2H), 7.40-7.50 (m, 1H), 3.47 (t, J = 6.7Hz, 2H), 3.29 (t, J = 6.7Hz, 2H); 13 C NMR (100MHz, CDCl3): δ196.50, 146.29, 139.61, 134.76, 131.26 (q, J=304.0Hz, 1C), 128.97, 128.57, 128.36, 127.34, 127.23, 38.91, 23.91; 19 FNMR (375MHz, CDCl3): δ-41.48.

[0076] Example 8:

[0077]

[0078] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(3-chlorophenyl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a colorless oily product (43.0 mg, yield: 53%).

[0079] NMR data: 1H NMR (400MHz, CDCl3): δ7.92 (t, J=4.0Hz, 1H), 7.83 (dt, J1=8.0Hz, J2=1.1Hz, 1H), 7.57 (dq, J1=8.0Hz, J2=1.0Hz, 1H), 7.43 (t, J=8.0Hz, 1H), 3.41 (t, J=6.8Hz, 2H), 3.25 (t, J=6.8 Hz, 2H); 13 C NMR (100MHz, CDCl3): δ195.71, 137.62, 135.19, 133.56, 131.18 (q, J=304.0Hz, 1C), 130.11, 128.12, 126.06, 39.10, 23.71; 19 F NMR (375MHz, CDCl3): δ-41.50.

[0080] Example 9:

[0081]

[0082] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(2-methoxyphenyl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a colorless oily product (52.5 mg, yield: 66%).

[0083] NMR data: 1 H NMR (400MHz, CDCl3): δ7.78 (dd, J1=4.0Hz, J2=8.0Hz, 1H), 7.50 (t, J=8.0Hz, 1H), 7.01 (q, J=8.0Hz, 2H), 3.92 (s, 3H), 3.44 (t, J=6.8Hz, 2H), 3.21 (t, J=6.8Hz, 2H); 13 C NMR (100 MHz, CDCl3): δ198.59, 159.03, 134.26, 131.32 (q, J=304.0Hz, 1C), 130.59, 126.78, 120.77, 111.59, 55.49, 44.06, 24.28; 19 F NMR (375MHz, CDCl3): δ-41.63.

[0084] Example 10:

[0085]

[0086] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-benzylcyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a colorless oily product (48.0 mg, yield: 64%).

[0087] NMR data: 1 H NMR (400MHz, CDCl3): δ7.35 (t, J=8.0Hz, 2H), 7.30 (d, J=8.0Hz, 2H), 7.20 (d, J=7.2Hz, 2H), 3.72 (s, 2H), 3.03 (t, J=6.8Hz, 2H), 2.88 (t, J=6.8Hz, 2H); 13 C NMR (100MHz, CDCl3): δ 205.23, 133.37, 131.07 (q, J=304.0Hz, 1C), 129.34, 128.88, 127.32, 50.13, 41.74, 23.43; 19 F NMR (375 MHz, CDCl3): δ-41.56.

[0088] Example 11:

[0089]

[0090] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(thiophene-3-yl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a yellow oily product (51.0 mg, yield: 71%).

[0091] NMR data:1 H NMR (400MHz, CDCl3): δ8.08 (s, 1H), 7.55 (d, J=8.0Hz, 1H), 7.34 (dd, J1=4.7Hz, J2=2.8Hz, 1H), 3.34 (d, J=6.8Hz, 2H), 3.23 (d, J=6.8Hz, 2H); 13 C NMR (100MHz, CDCl3): δ191.13, 141.36, 132.36, 131.18 (q, J=304.0Hz, 1C), 126.73, 126.61, 39.88, 23.69; 19 F NMR (375MHz, CDCl3): δ -41.49.

[0092] Example 12:

[0093]

[0094] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(furan-3-yl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a colorless oily product (36.3 mg, yield: 54%).

[0095] NMR data: 1 H NMR (400MHz, CDCl3): δ8.05 (s, 1H), 7.46 (s, 1H), 6.78 (s, 1H), 3.21 (s, 4H); 13 CNMR (100MHz, CDCl3): δ191.48, 147.35, 144.49, 131.17 (q, J=304.0Hz, 1C), 127.19, 108.42, 40.34, 23.59; 19 F NMR (375MHz, CDCl3): δ-41.49.

[0096] Example 13:

[0097]

[0098] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(2-naphthyl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (52.7 mg, yield: 62%).

[0099] NMR data: 1 H NMR (400MHz, CDCl3): δ8.47 (s, 1H), 8.02 (dd, J1=8.6Hz, J2=1.7Hz, 1H), 7.98 (d, J=8.0Hz, 1H), 7.91 (t, J=8.9Hz, 2H), 7.63 (td, J1=6.9Hz, J2=1.3Hz, 1H), 7.57 (td, J1=8.2Hz, J2= 1.4Hz, 1H), 3.58 (t, J=6.8Hz, 2H), .3.32 (t, J=6.8Hz, 2H); 13 CNMR (100MHz, CDCl3): δ196.85, 135.82, 133.50, 132.47, 131.29 (q, J=304.0Hz, 1C), 129.60, 128.76, 128.68, 127.82, 126.97, 123.51, 38.99, 24.02; 19 F NMR (375MHz, CDCl3): δ-41.46.

[0100] Example 14:

[0101]

[0102] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube, followed by S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(1-methyl-1H-indol-5-yl)cyclopropanol (0.3 mmol). The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (59.5 mg, yield: 69%).

[0103] NMR data: 1 H NMR (400MHz, CDCl3): δ8.29 (d, J=1.3Hz, 1H), 7.89 (dd, J1=8.7Hz, J2=1.6Hz, 1H), 7.36 (d, J=8.7Hz, 1H), 7.13 (d, J=3.1Hz, 1H), 6.62 (d, J=3.1Hz, 1H), 3.83 (s, 3H), 3.51 (d, J=6.9 Hz, 2H), 3.30 (d, J=6.8Hz, 2H); 13 C NMR (100MHz, CDCl3): δ195.80, 139.33, 131.35 (q, J=304.0Hz, 1C), 130.63, 128.29, 127.93, 122.77, 121.49, 109.25, 103.08, 38.57, 33.02, 24.30; 19 F NMR (375MHz, CDC13): δ-41.52.

[0104] Example 15:

[0105]

[0106] Under nitrogen protection, anhydrous copper acetate (0.09 mmol) as catalyst, 2-iodobenzoic acid (0.09 mmol) as oxidant, and 2 mL of acetonitrile were added to a 10 mL reaction tube. Then, S-trifluoromethyl-4-methylthiobenzenesulfonate (0.54 mmol) and 1-(1-1-(benzo[b]thiophene-3-yl)cyclopropanol (0.3 mmol) were added. The mixture was stirred in an oil bath at 40 °C for 12 h. After the reaction was complete, the mixture was transferred to a 10 mL round-bottom flask, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography (eluting with petroleum ether:ethyl acetate = 50:1) to give a white solid product (43.5 mg, yield: 50%).

[0107] NMR data: 1 H NMR (400MHz, CDCl3): δ8.75 (d, J=8.0Hz, 1H), 8.30 (t, J=1.8Hz, 1H), 7.88 (d, J= 8.2Hz, 1H), 7.51 (t, J=7.9Hz, 1H), 7.44 (t, J=7.2Hz, 1H), 3.46 (t, J=6.7Hz, 2H), 3.30 (t, J=6.7Hz, 2H); 13C NMR(100MHz,CDCl3):δ191.84,139.74,137.19,136.31,134.46,131.24(q,J=304.0Hz,1C), 126.01,125.65,125.52,122.27,40.05,23.90; 19 F NMR(375MHz,CDCl3):δ-41.43。

Claims

1. A process for the synthesis of β-trifluoromethylsulfenyl ketone derivatives from cyclopropanol derivatives by ring opening, characterized in that, The reaction is as follows: wherein R1 is phenyl, p-methylphenyl, p-fluorophenyl, p-chlorophenyl, p-bromophenyl, p-methoxyphenyl, biphenyl, m-chlorophenyl, o-methoxyphenyl, benzyl, thienyl, furanyl, naphthyl, indolyl, benzothienyl.

2. The process for synthesis of β-trifluoromethylthio ketone derivatives by ring opening of cyclopropanol derivatives according to claim 1, wherein: Specific steps: under anhydrous and anaerobic conditions, add anhydrous copper acetate, 2-iodoxybenzoic acid, acetonitrile, cyclopropyl alcohol derivative and S-trifluoromethyl-4-methylthiobenzenesulfonic acid thioester, react in a 40°C oil bath for 12 hours, after the reaction is completed, remove the solvent by reduced pressure distillation and separate by column chromatography to obtain trifluoromethylthio ketone derivative.

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