Alkyl trifluoromethyl thioether compound and synthesis method thereof

Abstract

The invention relates to the fields of medicine, organic chemical industry and fine chemical industry, in particular to an alkyl trifluoromethyl thioether compound and a synthesis method thereof. The method comprises the following steps: by taking non-activated olefin as a substrate, N-trifluoromethyl thiosaccharin or N-trifluoromethylthio phthalimide as a trifluoromethylthio source and cyclohexyl mercaptan, p-methylthiophenol or methyl 2-mercaptoacetate as a hydrogen source under the protection of inert gas, adding an inorganic alkali and an organic photocatalyst into a reaction system, and reacting under the conditions of blue light irradiation and room temperature, thereby obtaining the target product. Different substituted alkane trifluoromethyl thioether compounds are synthesized. The trifluoromethylthiolation reagent used in the method is easy to prepare and good in stability, participation of precious metal silver salt is avoided, and a 7.5% sodium hypochlorite solution is used for post-treatment to remove incompletely reacted mercaptan. The synthesis reaction conditions are mild, the reaction efficiency is high, the regioselectivity is good, the universality is excellent, and the functional group compatibility is good.

Description

Technical Field

[0001] The invention relates to the fields of medicine, organic chemical industry and fine chemical industry, and in particular to an alkyl trifluoromethyl sulfide compound and a synthesis method thereof. Background Art

[0002] Trifluoromethylthio (SCF3) has a high lipophilic constant (Hansch constant SCF3: 1.44). Introducing it into the drug molecule skeleton can greatly improve the ability of drug molecules to penetrate cell membranes and enhance the absorption and utilization of active ingredients of drugs by organisms. In addition, trifluoromethylthio has a strong electron-withdrawing ability (Hammett constant SCF3: σ p =0.50,σ m =0.40), its existence causes the electron cloud density and polarity of the molecular skeleton to change accordingly, thereby improving the pharmacokinetic effect (Xu, X.-H.; Matsuzaki, K.; Shibata, N. Chem. Rev. 2015, 115, 731-764.).

[0003] However, there is currently no efficient and mild method to synthesize drug molecules containing alkyl trifluoromethylthio groups. Traditional methods mainly rely on halogen-fluorine exchange or trifluoromethylation of thiols. Recently, visible light-promoted redox reactions have been used to directly trifluoromethylthiolate C-H bonds to synthesize various alkyl trifluoromethyl sulfide compounds (Mukherjee, S.; Maji, B.; Tlahuext-Aca A.; Glorius, F. Am. Chem. Soc. 2016, 138, 50, 16200-16203; Xu, W.; Ma, J.; Yuan, X.-A.; Dai, J.; Xie J.; Zhu, C. Angew. Chem. Int. Ed. 2018, 57, 10357-10361; Zhang, H.; Wang, Q.; Wang, Y.; Yuan, Z.; Gao, F.; Britto, R. Asian J. Org. Chem. 2021, 10, 2570.). Although these synthetic strategies have made significant progress, it is still difficult to control the regioselective trifluoromethylthiolation of alkyl groups due to their multiple carbon-hydrogen bonds. In existing reports, organic workers have used alkyl carboxylic acids, alkyl dihydropyridines, etc. as alkyl radical sources to synthesize alkyl trifluoromethyl sulfide compounds (Candish, L.; Pitzer, L.; A.; Glorius, F. Chem. Eur. J. 2016, 22, 4753-4756; Lipp, A.; Badir, SO; Gutierrez, O. Molander, GA Adv. Synth. Catal. 2021, 363, 3507-3520). However, some of these strategies use noble metal iridium complexes as photosensitizers, which does not conform to the synthetic concept of green chemistry. Some reactions have poor atom economy and low atom utilization. Summary of the invention

[0004] The purpose of the present invention is to provide a green and simple method for synthesizing alkyl trifluoromethyl sulfide. The method comprises the following steps: using nitrogen as an inert atmosphere, adding an inorganic base, an organic photocatalyst, a non-activated olefin (compound 1), a trifluoromethylsulfide source (compound 2) and a free radical hydrogen source (compound 3) into a reaction solvent; irradiating the reaction solvent with blue light, causing the non-activated olefin, the trifluoromethylsulfide source and the free radical hydrogen source to undergo a three-component reaction under the catalysis of the organic photocatalyst, and then performing post-treatment to obtain alkyl trifluoromethyl sulfide compounds with different substitutions.

[0005] The method of the invention uses cheap carbazole molecules or organic dye molecules as organic photosensitizers, and the reaction has significant advantages such as mild reaction conditions, little environmental pollution, simple operation, and good tolerance of reaction functional groups.

[0006] The specific process of the reaction is as follows:

[0007]

[0008] Among them, the R group can be The aromatic ring para-substituent R' is methyl, ethyl, isopropyl, methoxy, bromine, or chlorine. The R group can also be R 1 It may be cyclohexyl, 4-methylphenyl, or methyl acetate.

[0009] The above reaction conditions are: under nitrogen protection, at room temperature, irradiated with KESSILE blue light (45W), and the synthesis was carried out for 18 hours.

[0010] The reaction solvents are: N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), acetonitrile (MeCN);

[0011] The free radical hydrogen source is: R 1 -SH, R 1 It can be cyclohexyl, 4-methylphenyl, methyl acetate;

[0012] The trifluoromethylthio source is: N-trifluoromethylthiosaccharin or N-trifluoromethylthiophthalimide;

[0013] Inorganic bases are: dipotassium hydrogen phosphate (K2HPO4), potassium dihydrogen phosphate (KH2PO4), disodium hydrogen phosphate (Na2HPO4), and sodium dihydrogen phosphate (NaH2PO4).

[0014] The photocatalysts used are: 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN), 2,4,5-tris(9-carbazolyl)-6-(N-methylanilino)isophthalonitrile (3CzMPAIPN), and eosin Y. The amount of organic photocatalyst used is 2 mmol% of the molar number of non-activated olefins.

[0015] The molar ratio of the non-activated olefin, the trifluoromethylsulfenyl source and the free radical hydrogen source is 1:2:1.

[0016] The general structural formula of the obtained alkyl trifluoromethyl sulfide compound is: The R group can be The aromatic ring para-substituent R' is methyl, ethyl, isopropyl, methoxy, bromine, or chlorine. The R group can be

[0017] The three-component reaction post-treatment of the present invention uses a sodium hypochlorite solution with a content of 7.5% to remove the unreacted thiol; then only simple thin layer chromatography is needed for separation and purification, and petroleum ether: ethyl acetate = 70:1-50:1 is used as a developing solvent for thin layer chromatography separation, and the product is then concentrated under reduced pressure to remove the solvent to obtain a pure alkyl trifluoromethyl sulfide compound.

[0018] Beneficial effects:

[0019] The present invention avoids the use of precious metal photosensitive catalysts, uses cheap 4CzIPN, 3CzMPAIPN, and eosin YEosin Y as photocatalysts, and the catalyst is easy to prepare and has high catalytic efficiency; uses non-activated olefins with a wide range of industrial sources as substrates, and can achieve highly regioselective anti-Markovnikov hydrotrifluoromethylthiolation of non-activated olefins under mild photoredox conditions. In addition, the obtained alkyl trifluoromethyl sulfide compound can be further oxidized to obtain trifluoromethyl alkyl sulfone or trifluoromethyl alkyl sulfonimide, which can be used as an important synthetic intermediate. DETAILED DESCRIPTION

[0020] The reaction raw material N-trifluoromethylthiosaccharin or N-trifluoromethylthiophthalimide of the present invention is synthesized according to the literature (Xu, C.; Ma, B.; Shen, Q. Angew. Chem. Int. Ed. 2014, 53, 9316-9320; Xing, S.; Zhu, Y.-Y.; Liu, W.; et al. al.Org.Lett.2022,24,3378-3383.); another raw material olefin is a commercially available product or obtained by condensation of the corresponding carboxylic acid and alkenyl alcohol; the free radical hydrogen source is a commercially available product, including cyclohexyl mercaptan, p-methylbenzenethiol, and methyl 2-mercaptoacetate; the photocatalyst 4CzIPN is synthesized according to the literature (Huang, H.; Yu, C.; Zhang, Y. et al. J. Am. Chem. Soc. 2017, 139, 9799-9802); the reaction solvent is a commercially available product.

[0021] The present invention will be described in detail below with examples, and each reaction is shown in the following formula:

[0022]

[0023] Example 1

[0024] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 90%. 1 H NMR (400MHz, CDCl3) δ8.02-7.87(m,2H),7.30-7.24(m,2H),4.39-4.31(m,2H),2.99(t,J=6.8Hz,2H),2.44(s,3H),1.97-1.87(m,4H).

[0025] Example 2

[0026] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 3CzMPAIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 53%.

[0027] Example 3

[0028] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), Eosin Y (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 17%.

[0029] Example 4

[0030] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiophthalimide (2b, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), KH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 71%.

[0031] Example 5

[0032] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), DMF (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 28%.

[0033] Example 6

[0034] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), DMSO (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 33%.

[0035] Example 7

[0036] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), p-methylthiophenol (3b, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 7%.

[0037] Example 8

[0038] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), methyl 2-mercaptoacetate (3c, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 18%.

[0039] Example 9

[0040] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), Na2HPO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 72%.

[0041] Example 10

[0042] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), K2HPO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 55%.

[0043] Embodiment 11

[0044] 3-Butenyl p-methylbenzoate (1a, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), KH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4a was separated by thin layer chromatography, with a yield of 79%.

[0045] Example 12

[0046] 3-Butenyl p-ethylbenzoate (1b, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4b was separated by thin layer chromatography, with a yield of 80%. 1 H NMR (400MHz, CDCl3) δ7.95 (d, J = 8.2Hz, 2H), 7.29-7.26 (m, 2H), 4.41-4.31 (m, 2H), 2. 96(t,J=6.7Hz,2H),2.71(q,J=7.6Hz,2H),1.94-1.85(m,4H),1.26(t,J=7.6Hz,3H).

[0047] Example 13

[0048] 3-Butenyl p-isopropylbenzoate (1c, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4c was separated by thin layer chromatography, with a yield of 76%. 1 H NMR (400MHz, CDCl3) δ8.00-7.92(m,2H),7.34-7.28(m,2H),4.37-4.32(m,2H),3.02-2.92(m,3H),1.92-1.83(m,4H),1.27(d,J=6.9Hz,6H).

[0049] Embodiment 14

[0050] Add 3-butenyl p-methoxybenzoate (1d, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) to a Schlenk reaction tube, and perform gas replacement so that the reaction is carried out under nitrogen protection. Place the reaction tube under blue light irradiation, and the reaction time is 18h at room temperature. After the reaction is completed, add 2mL of acetonitrile, and then add 0.5mL of 7.5% sodium hypochlorite solution, and stir at room temperature for 30 minutes. Then separate the liquids, collect the organic phase, and then concentrate under reduced pressure to obtain a crude product, and then separate the target product 4d by thin layer chromatography, with a yield of 81%. 1 H NMR (400MHz, CDCl3) δ8.03-7.96(m,2H),6.95-6.89(m,2H),4.36-4.27(m,2H),3.86(s,3H),2.96(t,J=6.6Hz,2H),1.94-1.82(m,4H).

[0051] Embodiment 15

[0052] 3-Butenyl p-bromobenzoate (1e, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4e was separated by thin layer chromatography, with a yield of 75%. 1 H NMR (400MHz, CDCl3) δ7.95-7.86(m,2H),7.62-7.55(m,2H),4.35(t,J=5.9Hz,2H),2.96(t,J=6.7Hz,2H),1.92-1.86(m,4H).

[0053] Example 16

[0054] 3-Butenyl p-chlorobenzoate (1f, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4f was separated by thin layer chromatography, with a yield of 78%. 1 H NMR (400MHz, CDCl3) δ8.07-7.90(m,2H),7.50-7.37(m,2H),4.35(t,J=6.0Hz,2H),2.96(t,J=6.7Hz,2H),1.99-1.82(m,4H).

[0055] Embodiment 17

[0056] 1-naphthoic acid-3-butenyl ester (1g, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4g was obtained by thin layer chromatography, and the yield was 76%. 1 H NMR (400MHz, CDCl3) δ8.90(d,J=8.7Hz,1H),8.20-8.15(m,1H),8.03(d,J=8.2Hz,1H),7.89(d,J=7.4Hz,1 H),7.65-7.59(m,1H),7.57-7.48(m,2H),4.44(t,J=5.9Hz,2H),2.98(t,J=6.8Hz,2H),2.02-1.85(m,4H).

[0057] Embodiment 18

[0058] 2-(Alkenylbutyloxy)naphthalene (1h, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4h was obtained by thin layer chromatography, with a yield of 67%. 1 H NMR (400MHz, CDCl3) δ8.22(d,J=8.6Hz,1H),7.86-7.71(m,3H),7.57(t,J=7.7Hz,1H),7.41( t,J=7.7Hz,1H),7.38-7.26(m,1H),4.26-4.16(m,2H),3.09-3.00(m,2H),2.06-1.98(m,4H).

[0059] Embodiment 19

[0060] 9-(3-Butenyl)-carbazole (1i, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2ml of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4i was obtained by thin layer chromatography, with a yield of 91%. 1 H NMR (400MHz, CDCl3) δ8.12-8.10(m,2H),7.51(t,J=7.7Hz,1H),7.49-7.32(m,3H),7.31-7.2 1(m,2H),4.44(t,J=6.7Hz,2H),2.85(t,J=6.9Hz,2H),2.36-2.23(m,2H),1.33-1.23(m,2H).

[0061] Embodiment 20

[0062] N-(3-Butenyl)benzamide (1j, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4j was obtained by thin layer chromatography, with a yield of 90%. 1 H NMR (400MHz, CDCl3) δ7.80-7.72(m,2H),7.53-7.46(m,1H),7.45-7.39(m,2H) ,6.32(s,1H),3.48(q,J=6.4Hz,2H),2.92(t,J=6.8Hz,2H),1.81-1.71(m,4H).

[0063] Embodiment 21

[0064] 5-(But-3-ene-1-ylthio)-1-methyl-1H-tetrazole (1k, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to the Schlenk reaction tube, and the gas was replaced so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 4k was obtained by thin layer chromatography, with a yield of 49%. 1 H NMR (400MHz, CDCl3) δ3.91 (s, 3H), 3.36 (t, J = 7.1Hz, 2H), 2.92 (t, J = 7.1Hz, 2H), 2.00-1.91 (m, 2H), 1.90-1.82 (m, 2H).

[0065] Embodiment 22

[0066] 2-((tert-butyldiphenylsilyl)oxy)propylene (11, 0.1mmol), N-trifluoromethylthiosaccharin (2a, 0.2mmol), cyclohexyl mercaptan (3a, 0.1mmol), NaH2PO4 (0.1mmol), MeCN (1mL), 4CzIPN (2mmol%) were added to a Schlenk reaction tube, and gas replacement was performed so that the reaction was carried out under nitrogen protection. The reaction tube was placed under blue light irradiation and the reaction time was 18h at room temperature. After the reaction was completed, 2mL of acetonitrile was added, and then 0.5mL of 7.5% sodium hypochlorite solution was added, and stirred at room temperature for 30 minutes. Then the liquid was separated, and the organic phase was collected, and then the crude product was obtained by vacuum concentration, and then the target product 41 was obtained by thin layer chromatography, with a yield of 50%. 1 H NMR (400MHz, CDCl3) δ7.72-7.61(m,4H),7.44(d,J=7.0Hz,1H),7.43-7.40(m,2H),7.39(d,J=1.5Hz,2H ),7.37(d,J=1.8Hz,1H),3.67(t,J=6.1Hz,2H),2.86(t,J=7.4Hz,2H),1.72-1.62(m,2H),1.06(s,9H).

[0067] Embodiment 23

[0068] 4-Methylbenzoic acid (4-(trifluoromethylthio))butyl ester (4a, 0.1mmol), m-chloroperbenzoic acid (0.5mmol), and DCM (1mL) were added to a Schlenk reaction tube. The reaction time was 1h at room temperature. After the reaction, 2mL of 20% sodium thiosulfate aqueous solution was added, and the mixture was stirred at room temperature for 0.5h. DCM was then added for extraction, and the mixture was separated. The organic phase was collected and concentrated under reduced pressure to obtain a crude product, which was then separated by thin layer chromatography to obtain the target product trifluoromethyl alkyl sulfone 5 with a yield of 82%. 1 H NMR (400MHz, CDCl3) δ7.91(d,J=7.9Hz,2H),7.25(d,J=7.9Hz,2H),4.37(t,J=6.0 Hz,2H),3.33(t,J=7.8Hz,2H),2.41(s,3H),2.17-2.09(m,2H),2.03-1.95(m,2H).

[0069] Embodiment 24

[0070] 4-Methylbenzoic acid (4-(trifluoromethylthio))butyl ester (4a, 0.1mmol), ammonium carbamate (0.2mmol), iodophenyl diacetic acid (0.3mmol), trifluoroethanol (1mL) were added to a Schlenk reaction tube. The reaction time was 6h at room temperature. After the reaction was completed, the crude product obtained by vacuum concentration was dissolved in a mixed solvent of 6M hydrochloric acid and acetonitrile and stirred at room temperature for 12h. After the reaction was completed, saturated sodium bicarbonate solution was added to neutral, and then DCM was added for extraction, and the organic phase was collected and concentrated under reduced pressure to obtain a crude product, which was then separated by thin layer chromatography to obtain the target product trifluoromethyl alkyl sulfonyl imide 6 with a yield of 77%. 1 H NMR (400MHz, CDCl3) δ7.48-7.44(m,3H),7.30(s,1H),7.30-7.28(m,2H),7.27-7.23(m,2H),7.19(dd,J=7.6,1.9 Hz,2H),5.98(s,1H),4.57(s,2H),2.19(s,3H).

Claims

1. An alkyl trifluoromethyl sulfide compound, characterized in that The structural formula of the alkyl trifluoromethyl sulfide compound is: Among them, R is The aromatic ring para-substituent R' is methyl, ethyl, isopropyl, methoxy, bromine, or chlorine, or R is 2. A method for synthesizing the alkyl trifluoromethyl sulfide compound according to claim 1, characterized in that: The synthesis method steps are as follows: (1) under nitrogen protection, adding an inorganic base, an organic photocatalyst, a non-activated olefin, a trifluoromethylthio source and a free radical hydrogen source into a reaction solvent; (2) Under blue light irradiation, under the catalysis of an organic photocatalyst, a three-component reaction occurs among an unactivated olefin, a trifluoromethylsulfide source and a free radical hydrogen source, and then after post-treatment, alkyl trifluoromethyl sulfide compounds with different substitutions are obtained.

3. The method for synthesizing an alkyl trifluoromethyl sulfide compound according to claim 2, characterized in that: The reaction solvent is: N,N-dimethylformamide, dimethyl sulfoxide, and acetonitrile.

4. The method for synthesizing an alkyl trifluoromethyl sulfide compound according to claim 2, characterized in that: The inorganic base is: dipotassium hydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate NaH2PO4, and the amount of the inorganic base is 1 equivalent.

5. The method for synthesizing an alkyl trifluoromethyl sulfide compound according to claim 2, characterized in that: The structural formula of the non-activated olefin is Among them, R is The aromatic ring para-substituent R' is methyl, ethyl, isopropyl, methoxy, bromine, chlorine, or R is 6. The method for synthesizing an alkyl trifluoromethyl sulfide compound according to claim 2, characterized in that: The trifluoromethylthio source is: N-trifluoromethylthiosaccharin or N-trifluoromethylthiophthalimide.

7. The method for synthesizing an alkyl trifluoromethyl sulfide compound according to claim 2, characterized in that: The structural formula of the free radical hydrogen source is: R 1 -SH; wherein R1 is cyclohexyl, 4-methylphenyl, or methyl acetate.

8. The method for synthesizing an alkyl trifluoromethyl sulfide compound according to claim 2, characterized in that: The organic photocatalyst is: 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile 4CzIPN, 2,4,5-tris(9-carbazolyl)-6-(N-methylanilino)isophthalonitrile 3CzMPAIPN, and eosin Y. The amount of the organic photocatalyst is 2 mol% of the molar number of the non-activated olefin.

9. The method for synthesizing an alkyl trifluoromethyl sulfide compound according to claim 2, characterized in that: The molar ratio of the non-activated olefin, the trifluoromethylthio source and the free radical hydrogen source is 1:2:

1.

10. The method for synthesizing an alkyl trifluoromethyl sulfide compound according to claim 2, characterized in that: The three-component reaction conditions are: the synthesis is carried out for 18 hours at room temperature; and a 7.5% sodium hypochlorite solution is used for post-reaction treatment of the three-components to remove the unreacted thiol.

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