Preparation method of trimethyl-1, 1, 1-trifluoromethyl allyloxy silane and anti-tumor activity of trimethyl-1, 1, 1-trifluoromethyl allyloxy silane

Abstract

The invention discloses a preparation method of a trimethyl-1, 1, 1-trifluoromethyl allyloxy silane compound, and relates to the field of preparation of related products of pharmacy, agriculture and the like, in particular to preparation of the trimethyl-1, 1, 1-trifluoromethyl allyloxy silane compound by introducing a trifluoromethyl functional group into a carbonyl site of an alpha, beta-unsaturated ketone compound. The preparation method of the trimethyl-1, 1, 1-trifluoromethyl allyloxy silane comprises the following steps: by taking an alpha, beta unsaturated ketone compound as a raw material, adding a corresponding reaction reagent and catalyzing by microwave, thereby quickly obtaining a target product with high yield. According to the trimethyl-1, 1, 1-trifluoromethyl allyloxy silane compound provided by the invention, the preparation method is simple and easy, the yield is excellent, and a new thought is provided for trifluoromethylation reaction. The compound is proved to have good biological activity, can effectively inhibit the growth of human prostate tumor cells (PC-3), and has excellent anti-tumor potential.

Description

Technical Field

[0001] The invention relates to the preparation of pharmaceutical, agricultural and other related products, and in particular to the introduction of a trifluoromethyl functional group into the carbonyl position of an α,β-unsaturated ketone compound to prepare a trimethyl-1,1,1-trifluoromethylallyloxy silicon compound. Background Art

[0002] In the field of medicine, trifluoromethyl compounds can treat cancer, malaria, AIDS, tuberculosis, depression, etc. In the field of biologically active molecules, trifluoromethyl compounds show antiplatelet, antituberculosis, antibacterial and anti-inflammatory activities, and studies have found that replacing the methyl group in the molecule with trifluoromethyl can increase the biological activity of the original compound by an order of magnitude. The method of introducing trifluoromethyl into molecules is relatively mature, including using CF3 - Nucleophilic addition reaction with carbonyl group is a common method. The literature (DOI: 10.1016 / j.tet.2017.10.021) reported that when trimethyl trifluoromethylsilane (TMSCF3) was used as trifluoromethylation reagent, MgCl2 was used as catalyst, DMF was used as solvent, and the reaction was carried out for 2h. The yield of the product (2V) similar to the present invention reached 74%; the literature (DOI: 10.1016 / j.tetlet.2008.05.053) reported that When TMSCF3 is used as a trifluoromethylation reagent, TTMPP is used as a catalyst, and DMF is used as a solvent for reaction for 1 hour, the yield of the product similar to the present invention is (75%-92%); the document (DOI: 10.3390 / molecules22050769) reports that when TMSCF3 is used as a trifluoromethylation reagent, CsCO3 is used as a catalyst, and dichloromethane is used as a solvent for reaction for 36 hours, the yield of the product similar to the present invention is (77%-94%). At present, there is a lack of systematic research on the method of introducing trifluoromethyl into α,β-unsaturated carbonyl compounds in a green, rapid, and high-yield manner without solvent or catalyst. Summary of the invention

[0003] The present invention utilizes the property that microwave reaction can change the molecular dipole moment, and directly reacts α, β-unsaturated ketone compounds and TMSCF3 under microwave heating conditions to obtain a product in which C=O is directly added.

[0004] The structure of the trifluoromethylsilyl ether substance prepared by the present invention is:

[0005]

[0006] Wherein, R1 is selected from 4-Ph, 4-MePh, 4-OMePh, 2-naphthalene, 4-BrPh, 4-FPh, 2-thiophene, 2-furan; R2 is selected from 2-furan, 2-thiophene, 2-pyrazine, 2-thiazole, 4-CF3Ph.

[0007] Furthermore, the compound represented by formula I is selected from any one of the structures represented by formula II to VI below,

[0008]

[0009] Furthermore, in II, R3 = 4-H, 4-Me, 4-OMe, 2-naphthyl, 4-BrPh, 2-thiophene; in III, R4 = 4-F, 4-Br, 2-thiophene; in IV, R5 = 2-pyrazine, 2-thiazole; in V, R6 = 2-thiophene, 4-BrPh, 2-furan; in VI, R7 = CH3, CH3O.

[0010] Further, compound I is prepared from compound VII, i.e., an α,β-unsaturated carbonyl compound.

[0011]

[0012] Furthermore, the preparation method of compound II is: at 120°C, without solvent, at normal pressure, α,β-unsaturated ketone and trimethyltrifluoromethylsilane are reacted under 300W microwave conditions for 10 minutes, and after the reaction is completed, the temperature is gradually restored to room temperature, a small amount of water is added to quench the reaction, and ethyl acetate and saturated brine are used for extraction. The organic phase is concentrated to obtain a yellow oily solid with a yield of 85-96%.

[0013] Furthermore, the preparation method of compound III is: at 140°C, without solvent, α,β-unsaturated ketone and trimethyltrifluoromethylsilane are reacted under 300W microwave conditions for 10 minutes. After the reaction is completed, it is gradually restored to room temperature, a small amount of water is added to quench the reaction, ethyl acetate and saturated brine are extracted, and the organic phase is concentrated to obtain a yellow oily liquid with a yield of 78-83%.

[0014] Furthermore, the preparation method of compound IV is: at 140°C, without solvent, α,β-unsaturated ketone and trimethyltrifluoromethylsilane are reacted under 300W microwave conditions for 10 minutes, gradually returning to room temperature, the reaction is completed, extracted, and dried to obtain a colorless oily liquid with a yield of 91-95%.

[0015] Furthermore, the preparation method of compound V is: at 120°C, without solvent, α,β-unsaturated ketone and trimethyltrifluoromethylsilane are reacted under 300W microwave conditions for 10 minutes. After the reaction is completed, it is gradually restored to room temperature, a small amount of water is added to quench the reaction, ethyl acetate and saturated brine are extracted, and the organic phase is concentrated to obtain a red oily liquid with a yield of 75%.

[0016] Furthermore, the preparation method of compound VI is: at 140°C, without solvent, α,β-unsaturated ketone and trimethyltrifluoromethylsilane are reacted under 300W microwave conditions for 15 minutes. After the reaction is completed, it is gradually restored to room temperature, a small amount of water is added to quench the reaction, ethyl acetate and saturated brine are extracted, and the organic phase is concentrated to obtain a yellow oily liquid with a yield of 85-88%.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] 1) The present invention is the first to prepare a variety of trifluoromethylsilyl ether compounds by microwave catalysis.

[0019] 2) The preparation method of the present invention is simple, the reaction is rapid, and the post-treatment process is simple.

[0020] 3) The present invention has wide applicability, high yield and excellent practical value. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 IC of trimethyl-1,1,1-trifluoromethyl-3-(4-fluorophenyl)-1-(2-thiophene)allyloxysilane on PC-3 cells 50 image. DETAILED DESCRIPTION

[0022] The technical solution of the present invention is not limited to the specific implementation modes listed below, but also includes any combination of the specific implementation modes.

[0023] Specific embodiment 1: The structure of the trifluoromethylsilyl ether substance in this embodiment is:

[0024]

[0025] Wherein, R1 is selected from Ph, 4-MePh, 4-OMePh, 2-naphthalene, 4-BrPh, 4-FPh, 2-thiophene, 2-furan; R2 is selected from 2-furan, 2-thiophene, 2-pyrazine, 2-thiazole, 4-CF3Ph.

[0026] Specific embodiment 2: In this embodiment, the compound prepared is selected from any one of the structures shown in the following formulae II to VI:

[0027]

[0028] Among them, in II, R3 = 4-H, 4-Me, 4-OMe, 2-naphthyl, 4-BrPh, 2-thiophene. In III, R4 = 4-F, 4-Br, 2-thiophene. In IV, R5 = 2-pyrazine, 2-thiazole. In V, R6 = 2-thiophene, 4-BrPh, 2-furan. In VI, R7 = 4-MePh, 4-OMePh.

[0029] Specific implementation method three, the preparation method of trimethyl-1,1,1-trifluoromethyl-3-aryl-1-(2-furan)allyloxysilane II prepared in this implementation method is: at 120°C, without solvent, 1-(2-furanyl)-3-aryl propenone and trimethyltrifluoromethylsilane are reacted under 300W microwave conditions for 10 minutes, and after the reaction is completed, the temperature is gradually restored to room temperature, a small amount of water is added to quench the reaction, ethyl acetate and saturated brine are extracted, the organic phase is concentrated, and column chromatography is performed with n-hexane:ethyl acetate = 15:1 volume ratio Purification, to obtain trimethyl-1,1,1-trifluoromethyl-3-aryl-1-(2-furan)allyloxysilane yellow oil, the yield is 85-96%.

[0030] Specific embodiment 4. The preparation method of trimethyl-1,1,1-trifluoromethyl-3-aryl-1-(2-thiophene)allyloxysilane III prepared in this embodiment is as follows: at 140°C, without solvent, 1-(2-thiophene)-3-aryl propenone and trimethyltrifluoromethylsilane are reacted under 300W microwave conditions for 10 minutes. After the reaction is completed, the temperature is gradually restored to room temperature, a small amount of water is added to quench the reaction, ethyl acetate and saturated brine are extracted, the organic phase is concentrated, and column chromatography is performed with a volume ratio of n-hexane:ethyl acetate = 15:1 to purify trimethyl-1,1,1-trifluoromethyl-3-aryl-1-(2-thiophene)allyloxysilane, and the yield is 78-83%.

[0031] Specific embodiment 5. The preparation method of trimethyl-1,1,1-trifluoromethyl-3-(2-furan)allyloxysilane IV prepared in this embodiment is: at 140°C, without solvent, 1-aryl-3-(2-furanyl)propenone and trimethyltrifluoromethylsilane are reacted under 300w microwave conditions for 10 minutes, gradually restored to room temperature, the reaction is completed, extracted, dried, and purified by column chromatography with a volume ratio of n-hexane: ethyl acetate = 15:1 to obtain trimethyl-1,1,1-trifluoromethyl-3-(2-furan)allyloxysilane as a yellow oily liquid with a yield of 91-95%.

[0032] Specific embodiment six: The preparation method of trimethyl-1,1,1-trifluoromethyl-3-(2-thiophene)allyloxysilane V prepared in this embodiment is: at 120°C, without solvent, 1-(2-thiophene)-3-aryl propenone and trimethyltrifluoromethylsilane are reacted under 300w microwave conditions for 10 minutes. After the reaction is completed, the temperature is gradually restored to room temperature, a small amount of water is added to quench the reaction, ethyl acetate and saturated brine are extracted, the organic phase is concentrated, and column chromatography is performed with a volume ratio of n-hexane:ethyl acetate = 15:1 to purify trimethyl-1,1,1-trifluoromethyl-3-(2-thiophene)allyloxysilane. A red oily liquid with a yield of 75% is obtained.

[0033] Specific embodiment seven: The preparation method of trimethyl-1,1,1-trifluoromethyl-3-aryl-1-(4-trifluoromethyl)phenylallyloxysilane VI prepared in this embodiment is: at 140°C, without solvent, 1-(4-trifluoromethyl)phenyl-3-arylpropenone and trimethyltrifluoromethylsilane are reacted under 300W microwave conditions for 15 minutes, after the reaction is completed, gradually return to room temperature, add a small amount of water to quench the reaction, extract with ethyl acetate and saturated brine, concentrate the organic phase, and purify by column chromatography with a volume ratio of n-hexane:ethyl acetate=20:1 to obtain trimethyl-1,1,1-trifluoromethyl-3-aryl-1-(4-trifluoromethyl)phenylallyloxysilane as a yellow oily liquid with a yield of 85-88%.

[0034] The embodiments of the present invention are described in detail below. The following embodiments are implemented on the premise of the technical solution of the present invention, and detailed implementation schemes and specific operation processes are given, but the protection scope of the present invention is not limited to the following embodiments.

[0035] Example 1: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-phenyl-1-(2-furan)allyloxysilane, which is carried out according to the following steps: At room temperature, 0.29mmol of 1-(2-furanyl)-3-phenylpropenone and 0.64mmol of trifluoromethyltrimethylsilane are added to a 10mL thick-walled glass tube, placed in a microwave reactor, and the microwave power is adjusted to 300w, the reaction temperature is 120°, and the reaction is carried out at normal pressure for 10min. After the reaction is completed, it is cooled and the reaction is monitored by thin layer chromatography (n-hexane: ethyl acetate = 15:1). A small amount of water is added to quench the reaction, and ethyl acetate is extracted with saturated brine. After the organic phase is concentrated, 300-400 mesh silica gel powder is used for wet column, and the mobile phase ratio is n-hexane: ethyl acetate = 15:1 to obtain a yellow oily liquid with a yield of 93%. The structural data of trimethyl-1,1,1-trifluoromethyl-3-phenyl-1-(2-furan)allyloxysilane are: 1HNMR (300MHz, CDCl3) δ = 7.52 (m, J = 8.4, 3.7, 1.6Hz, 3H), 7.46–7.31 (m, 3H), 6 .97(d,J=15.8Hz,1H),6.59(d,J=3.4Hz,1H),6.56–6.45(m,2H),0.12(s,9H). 13 C NMR (75MHz, CDCl3) δ=149.92,142.90,135.77,134.49,128.72,128.47,127.52,127.06,125.98,124.37,122.19,111.16,111.13,110.81,1.02.

[0036] Example 2: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(4-methylphenyl)-1-(2-furan)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 1, except that 1-(2-furanyl)-3-phenylpropenone is replaced by 1-(2-furanyl)-3-(4-methyl)phenylpropenone. The final product yield is 89%. The structural data of trimethyl-1,1,1-trifluoromethyl-3-(4-methylphenyl)-1-(2-furan)allyloxysilane is: 1 H NMR (300MHz, CDCl3) δ7.51 (dd, J=1.8, 0.8Hz, 1H), 7.45–7.32 (m, 2H), 7.20 (d, J=7.9Hz, 2H), 6. 88(d,J=15.8Hz,1H),6.55(dt,J=3.3,0.7Hz,1H),6.52–6.25(m,2H),2.39(s,3H),0.09(s,9H). 13 C NMR (75MHz, CDCl3) δ142.85,138.43,134.38,132.96,129.39,126.95,123.24,111.11,110.75,1.04.

[0037] Example 3: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(4-methoxyphenyl)-1-(2-furan)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 1, except that 1-(2-furanyl)-3-phenylpropenone is replaced by 1-(2-furanyl)-3-(4-methoxy)phenylpropenone. The final product yield is 90%. The structural data of trimethyl-1,1,1-trifluoromethyl-3-(4-methoxyphenyl)-1-(2-furan)allyloxysilane is: 1H NMR (300MHz, CDCl3) δ7.62–7.33(m,3H),7.01–6.72(m,3H),6.55(dt,J=3.4,0.7Hz,1H ),6.46(dd,J=3.4,1.8Hz,1H),6.35(dt,J=15.9,0.9Hz,1H),3.85(s,3H),0.09(s,9H). 13 C NMR (75MHz, CDCl3) δ159.91,150.12,142.83,133.96,128.48,128.30,122.00,114.10,111.07,111.04,110.74,55.31,1.05.

[0038] Example 4: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(2-naphthyl)-1-(2-furan)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 1, except that 1-(2-furanyl)-3-phenyl-propenone is replaced by 1-(2-furanyl)-3-(4-bromo)phenylpropenone. The final product yield is 89%. The structural data of trimethyl-1,1,1-trifluoromethyl-3-(2-naphthyl)-1-(2-furan)allyloxysilane is: 1 H NMR(300MHz, CDCl3)δ7.89–7.80(m,4H),7.68(dd,J=8.6,1.7Hz,1H),7.58–7.43(m,3H ),7.08(d,J=15.8Hz,1H),6.71–6.55(m,2H),6.47(dd,J=3.4,1.8Hz,1H),0.11(s,9H). 13 C NMR (75MHz, CDCl3) δ142.93,134.53,133.50,133.14,128.41,128.12,127.70,127.53,126.45,126.31,124.61,123.64,111.17,110.82,1.06.

[0039] Example 5: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(4-bromophenyl)-1-(2-furan)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 1, except that 1-(2-furanyl)-3-phenylpropenone is replaced with 1-(2-furanyl)-3-(2-naphthyl)phenylpropenone. The final product yield is 89%. The structural data of trimethyl-1,1,1-trifluoromethyl-3-(4-bromophenyl)-1-(2-furan)allyloxysilane is: 1H NMR (300MHz, CDCl3) δ7.54–7.46(m,3H),7.37–7.31(m,2H),6.85(d,J=15.8Hz,1H),6.53(dt,J=3.4,0.8Hz,1H),6.50–6.35(m,2H),0.06(s,9H). 13 C NMR (75MHz, CDCl3) δ149.57,142.91,133.14,131.81,128.52,122.34,110.81,0.95.

[0040] Example 6: Preparation of trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-furanyl)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 1, except that 1-(2-furanyl)-3-phenylpropenone is replaced with 1-(2-furanyl)-3-(2-thienyl)propenone. The final product yield is 88%. The structural data of trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-furanyl)allyloxysilane is: 1 H NMR(300MHz,Chloroform-d)δ7.52(dd,J=1.9,0.8Hz,1H),7.33–7.20(m,1H),7.10(dd,J=3.7,1.2Hz,1H),7.0 6–6.92(m,2H),6.56(dt,J=3.5,0.7Hz,1H),6.46(dd,J=3.4,1.8Hz,1H),6.32(d,J=15.6Hz,1H),0.09(s,9H). 13 C NMR (75MHz, Chloroform-d) δ149.66,142.94,140.66,127.62,127.60,127.56,127.36,125.53,123.62,122.07,111.16,110.79,1.05.

[0041] Example 7: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(4-fluorophenyl)-1-(2-thiophene)allyloxysilane, which is carried out according to the following steps: At room temperature, 0.43 mmol of 1-(2-thienyl)-3-(4-fluoro)phenylpropenone and 0.94 mmol of trifluoromethyltrimethylsilane are added to a 10 mL thick-walled glass tube, placed in a microwave reactor, and the microwave power is adjusted to 300 w, the reaction temperature is 140°, and the reaction is carried out at normal pressure for 10 min. After the reaction is completed, the reaction is cooled and monitored by thin layer chromatography (n-hexane: ethyl acetate = 15:1). A small amount of water is added to quench the reaction, and the ethyl acetate is extracted with saturated brine. After concentrating the organic phase, 300-400 mesh silica gel powder is used for wet column chromatography. The mobile phase ratio is n-hexane: ethyl acetate = 15:1 to obtain a yellow oily liquid with a yield of 78%. The structural data of trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-furyl)allyloxysilane are: 1 H NMR(300MHz,Chloroform-d)δ7.60–7.47(m,2H),7.44–7.30(m,3H),7.20(m,J=3.2,1.0Hz,1H), 7.10(dd,J=5.1,3.7Hz,1H),6.85(d,J=15.9Hz,1H),6.61(dd,J=15.9,0.8Hz,1H),0.18(s,9H). 13 C NMR (75MHz, Chloroform-d) δ135.46,135.40,128.83,128.77,127.26,127.24,127.16,127.05,126.32,125.95,1.81.

[0042] Example 8: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(4-bromophenyl)-1-(2-thiophene)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 7, except that 1-(2-thiophene)-3-(4-fluoro)phenylpropenone is replaced by 1-(2-thiophene)-3-(4-bromo)phenylpropenone. The final product yield is 81%. The product trimethyl-1,1,1-trifluoromethyl-3-(4-bromophenyl)-1-(2-thiophene)allyloxysilane structure data is: 1 H NMR (300MHz, Chloroform-d) δ7.49–7.38(m,3H),7.25–7.17(m,1H),7.14–7.05(m,3H),6.88(d,J=16.0Hz,1H),6.55(d,J=16.0Hz,1H),0.19(s,9H). 13C NMR(75MHz,Chloroform-d)δ164.64,161.35,141.99,134.12,131.67,131.63,1 28.74,128.63,127.24,127.22,127.18,126.37,125.80,115.97,115.68,1.75.

[0043] Example 9: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-thiophene)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 7, except that 1-(2-thienyl)-3-(4-fluoro)phenylpropenone is replaced by 1-(2-thienyl)-3-(2-thienyl)propenone. The product yield is 80%. The structural data of the product trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-thiophene)allyloxysilane is: 1 H NMR(300MHz,Chloroform-d)δ7.42(dd,J=5.1,1.2Hz,1H),7.31(dt,J=5.1,1.0Hz,1H),7.22(dt ,J=3.7,1.1Hz,1H),7.17–7.08(m,2H),7.08–6.93(m,2H),6.49(d,J=15.8Hz,1H),0.24(s,9H). 13 C NMR (75MHz, Chloroform-d) δ141.92,140.42,128.81,127.90,127.76,127.24,127.21,127.19,126.37,126.03,125.13,1.82.

[0044] Example 10: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(4-bromophenyl)-1-(2-thiophene)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 7, except that 1-(2-thiophene)-3-(4-fluoro)phenylpropenone is replaced by 1-(2-thiophene)-3-(4-bromo)phenylpropenone. The product yield is 85%. The structural data of the product trimethyl-1,1,1-trifluoromethyl-3-(4-bromophenyl)-1-(2-thiophene)allyloxysilane is: 1 H NMR (300MHz, Chloroform-d) δ7.72–7.40(m,4H),7.30–7.27(m,1H),7.09–6.97(m,2H),6.77(d,J=16.2Hz,1H),6.35(d,J=16.2Hz,1H),0.19(s,9H). 13C NMR(75MHz,Chloroform-d)δ140.41,136.88,131.15,129.75,129.73,129.71,129.10,129.09,127.79,127.74,125.99,125.46,123.03,122.71,1.98.

[0045] Example 11: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(2-furyl)-1-(2-thiazole)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 7, except that 1-(2-thienyl)-3-(4-fluoro)phenylpropenone is replaced by 1-(2-thiazolyl)-3-(2-furyl)propenone. The product yield is 86%. The structural data of the product trimethyl-1,1,1-trifluoromethyl-3-(2-furyl)-1-(2-thiazole)allyloxysilane is: 1 H NMR (300MHz, Chloroform-d) δ7.44 (dd, J=7.7, 2.5Hz, 2H), 6.70 (d, J=15.9Hz, 1H), 6. 58(d,J=15.9Hz,1H),6.42(dd,J=3.4,1.8Hz,1H),6.38(d,J=3.3Hz,1H),0.23(s,9H). 13 C NMR(75MHz,Chloroform-d)δ170.31 143.59,143.23,129.18,123.55,122.69,122.18,120.84,111.57,111.00,1.80.

[0046] Example 12: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-thiazole)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 7, except that 1-(2-thienyl)-3-(4-fluoro)phenylpropenone is replaced by 1-(2-thiazolyl)-3-(2-thienyl)propenone. The product yield is 82%. The structural data of the product trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-thiazole)allyloxysilane is: 1 H NMR (300MHz, Chloroform-d) δ7.93(d,J=3.3Hz,1H),7.46(d,J=3.3Hz,1H),7.06(d,J=3.2Hz,1H),7.05–6.93(m,2H),6.46(d,J=15.9Hz,1H),0.24(s,9H). 13C NMR (75MHz, Chloroform-d) δ143.65,140.26,128.03,127.63,126.06,123.06,120.88,1.80.

[0047] Example 13: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-pyrazine)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 7, except that 1-(2-thienyl)-3-(4-fluoro)phenylpropenone is replaced by 1-(2-pyrazine)-3-(2-thienyl)propenone. The product yield is 75%. The structural data of the product trimethyl-1,1,1-trifluoromethyl-3-(2-thienyl)-1-(2-pyrazine)allyloxysilane is: 1 H NMR (300MHz, Chloroform-d) δ9.04(s,1H),8.69–8.52(m,2H),7.54–7.36(m,1H),6.73–6.53(m,2H),6.49–6.27(m,2H),0.19(s,9H). 13 C NMR (75MHz, Chloroform-d) δ151.22,144.55,144.12,143.08,142.90,123.29,123.26,111.55,110.56,1.94.

[0048] Example 14: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(4-trifluoromethylphenyl)-1-(4-methylphenyl)allyloxysilane, and the specific steps are as follows: At room temperature, 0.34 mmol of 1-(4-trifluoromethyl)phenyl-3-(4-methyl)phenylpropenone and 0.75 mmol of trifluoromethyltrimethylsilane are put into a 10 mL thick-walled glass tube, placed in a microwave reactor, and the microwave power is adjusted to 300 w, the reaction temperature is 120°, and the reaction is carried out at normal pressure for 10 min. After the reaction is completed, the reaction is cooled and monitored by thin layer chromatography (n-hexane: ethyl acetate = 15:1). A small amount of water is added to quench the reaction, and the ethyl acetate is extracted with saturated brine. After the organic phase is concentrated, 300-400 mesh silica gel powder is used for wet column chromatography. The mobile phase ratio is n-hexane: ethyl acetate = 15:1 to obtain a yellow oily liquid with a yield of 85%. The structural data of the product trimethyl-1,1,1-trifluoromethyl-3-(4-trifluoromethylphenyl)-1-(4-methylphenyl)allyloxysilane are: 1H NMR(300MHz,Chloroform-d)δ7.89–7.79(m,2H),7.78–7.69(m,2H),7.42–7.34(m,2H),7.25(d ,J=7.9Hz,2H),6.69(d,J=16.4Hz,1H),6.60(dd,J=16.4,0.9Hz,1H),2.43(s,3H),0.26(s,9H). 13 C NMR(75MHz,Chloroform-d)δ142.32,139.10,136.21,136.19,132.55,129.63,128.52, 128.50,126.81,125.90,125.01,124.95,124.90,124.85,124.80,122.93,21.21,1.99.

[0049] Example 15: This example is a method for preparing trimethyl-1,1,1-trifluoromethyl-3-(4-trifluoromethylphenyl)-1-(4-methoxyphenyl)allyloxysilane. All experimental conditions and treatment methods are the same as those in Example 14, except that 1-(4-trifluoromethyl)phenyl-3-(4-methyl)phenylpropenone is replaced by 1-(4-trifluoromethyl)phenyl-3-(4-methoxy)phenylpropenone, with a yield of 88%. The structural data of the product trimethyl-1,1,1-trifluoromethyl-3-(4-trifluoromethylphenyl)-1-(2-(4-methoxyphenyl))allyloxysilane is: 1 H NMR(300MHz,Chloroform-d)δ7.80(d,J=8.3Hz,2H),7.75–7.60(m,2H),7.49–7.34(m,2H),7.0 2–6.85(m,2H),6.61(d,J=16.4Hz,1H),6.48(dd,J=16.4,0.8Hz,1H),3.86(s,3H),0.23(s,9H). 13 C NMR(75MHz,Chloroform-d)δ160.33,142.33,135.83,130.51,128.52,128.51, 128.17,127.97,124.91,124.86,124.81,124.76,123.70,114.31,55.26,1.98.

[0050] Example 16: This example is a method for exploring the anti-tumor effect of trimethyl-1,1,1-trifluoromethyl-3-(4-fluorophenyl)-1-(2-thiophene) allyloxysilane. The MTT cell detection method is used. PC-3 cells are selected and sterilized by ultraviolet for 30 minutes. The control group is added with PC-3 cells without adding any chemical substances. The experimental group is added with 0.1umol / L, 1nmol / L, 10umol / L, 50umol / L, and 100umol / L of different concentration gradients of trimethyl-1,1,1-trifluoromethyl-3-(4-fluorophenyl)-1-(2-thiophene) allyloxysilane. After 36 hours, the survival rate of PC-3 cells is observed at a wavelength of 570nm, and the IC value of the substance on PC-3 cells is measured. 50 The value is 8.735. IC 50 See attached for details Figure 1 .

Claims

1. The present invention relates to a method for preparing trimethyl-1,1,1-trifluoromethylallyloxysilane compounds, characterized in that The method comprises the following steps: mixing α,β-unsaturated ketone with TMSCF3, and then, in a microwave reactor, under a certain power, without solvent, to obtain a trimethyl-1,1,1-trifluoromethylallyloxysilane compound with a yield of 70-95%. The trimethyl-1,1,1-trifluoromethylallyloxysilane compound has a structural formula of Among them, R1 is 4-Ph, 4-MePh, 4-OMePh, β-naphthalene ring, 4-BrPh, 4-FPh, 2-thiophene, 2-furan; R2 is 2-furan, 2-thiophene, 2-pyrazine, 2-thiazole, 4-CF3Ph.

2. The method for preparing trimethyl-1,1,1-trifluoromethylallyloxysilane compounds according to claim 1 is prepared under the condition that the microwave power is 200-300W.

3. The method for preparing trimethyl-1,1,1-trifluoromethylallyloxysilane compounds according to claim 1 is completed at a temperature of 100°C-150°C.

4. The method for preparing trimethyl-1,1,1-trifluoromethylallyloxysilane compounds according to claim 1, wherein the reaction time is 10-15 minutes.

5. According to claim 1, trimethyl-1,1,1-trifluoromethylallyloxysilane compounds have certain application prospects in the pharmaceutical field, and the application does not include direct implementation on living human / animal bodies for the purpose of treating diseases.

6. According to claim 5, trimethyl-1,1,1-trifluoromethylallyloxysilane compounds have a good inactivation effect on human prostate tumor cells PC-3, Ic50 = 8.735um / L.

Images