A method for synthesizing 4-trifluoroethyl-2-quinazolinones

Abstract

The application discloses a synthesis method of 4-trifluoroethyl-2-quinozolinone compound and belongs to the field of organic chemistry. The method can quickly realize one-pot synthesis of 4-trifluoroethyl-2-quinozolinone compound under blue light irradiation by using a novel trifluoromethyl copper complex, an ortho alkenyl aryl urea compound, potassium carbonate and potassium persulfate as reactants. The method has wide substrate applicability, simple raw materials and low economic cost. In addition, the method realizes synthesis of the target product, does not need to add a catalyst for catalysis, and can obtain the target product in a good yield only by reacting for 12 hours. The target compound has wide application in the fields of medicines, pesticides and the like.

Description

Technical Field

[0001] This invention relates to a method for synthesizing 4-trifluoroethyl-2-quinazolinone compounds, belonging to the field of organic chemistry. Background Technology

[0002] Trifluoromethyl (-CF3), as an important fluorine-containing functional group, possesses excellent lipophilicity, strong electron-withdrawing properties, and the resulting bioactivity, leading to its widespread application in organic synthesis, medicinal chemistry, materials science, and many other fields. The trifluoromethyl group is a highly favored functional group due to its stability and relatively easy chemical introduction. Furthermore, copper, with its low cost, relatively low toxicity, excellent stereoselectivity, and visible light photocatalysis, has played a crucial role in replacing noble metal catalysts. Considering the advantages of both, introducing the trifluoromethyl group by constructing trifluoromethyl copper complexes is a superior functional group modification strategy. However, the current types of trifluoromethyl copper complexes are limited, and the exploration of reactions suitable for trifluoromethyl functionalization is still relatively scarce. Quinazolinones are a class of heterocyclic compounds widely found in natural products, pharmaceuticals, and bioactive substances, belonging to a large category of alkaloids. They have wide applications in pesticides and pharmaceuticals, showing particular promise in antibacterial, antiviral, antidiabetic, and antituberculosis applications, especially in antitumor drug research. Traditionally, quinazolinones are synthesized by coupling 2-aminobenzamide with aldehydes, carboxylic acids, or carboxyl halides. However, these methods suffer from drawbacks such as limited product structure, poor atom economy, demanding reaction conditions, and difficulty in modifying functional groups.

[0003] Therefore, there is a need for a method for synthesizing quinazolinone compounds that is simple in procedure, has good atom economy, mild reaction conditions, and good reaction selectivity. Summary of the Invention

[0004] The first objective of this invention is to provide a method for synthesizing 4-trifluoroethyl-2-quinazolinone compounds, the method comprising: In an organic solvent, using the arylimine-type trifluoromethyl copper complex of formula (1), o-alkenylarylurea compounds, an oxidant, and a base as reactants, an addition cyclization reaction was carried out under blue light irradiation to synthesize the 4-trifluoromethyl-2-quinazolinone compound shown in formula (2):

[0005] Among them, R 1 Selected from H, C1 alkyl, halogen, cyano, nitro, C1 alkoxy, ester; R 2 Selected from C1 alkyl, C1 alkoxy, halogen, nitro, cyano, and acyl groups.

[0006] In one embodiment of the present invention, a pyridyl trifluoromethyl copper complex, 2,6-[1-methyl-2-( N [-benzylimine]pyridine and dichloromethane were used as reactants to synthesize an arylimine-type trifluoromethyl copper complex.

[0007] In one embodiment of the present invention, the reaction conditions for synthesizing the arylimine-type trifluoromethyl copper complex of formula (1) are: at room temperature and pressure, the reaction is carried out at 200 rpm to 500 rpm for 0.5 to 2 h. Preferably, the reaction is carried out at 400 rpm for 1 h.

[0008] In one embodiment of the present invention, the organic solvent includes N,N - One or more of dimethylformamide (DMF), acetonitrile (CH3CN), dichloromethane (DCM), and tetrahydrofuran (THF). DMF is preferred.

[0009] In one embodiment of the present invention, the oxidant includes potassium persulfate, N - One or more of fluorobisbenzenesulfonamide, sodium persulfate, and cerium ammonium nitrate. Potassium persulfate is preferred.

[0010] In one embodiment of the present invention, the alkali includes any one or more of potassium carbonate, sodium bicarbonate, sodium hydroxide, potassium tert-butoxide, and sodium carbonate. Potassium carbonate is preferred.

[0011] In one embodiment of the invention, the blue light has a wavelength of 365 nm or 390 nm. Preferably, it is 390 nm.

[0012] In one embodiment of the invention, the synthesis reaction is carried out at a distance of 3 to 10 cm from the blue light source. Preferably, it is 5 cm.

[0013] In one embodiment of the invention, the reaction temperature is 25~50°C, preferably 25~39°C.

[0014] In one embodiment of the present invention, the reaction time is 8 to 24 hours. Specifically, 12 hours may be selected.

[0015] In one embodiment of the present invention, the molar ratio of the arylimine-type trifluoromethyl copper complex, the o-alkenylarylurea compound, the oxidant, and the base is 1:(1.0~2.0):(1.0~2.0):(1.0~2.0). Preferably, it is 1.0:1.5:2.0:1.2.

[0016] In one embodiment of the present invention, the reaction concentration of the arylimine-type trifluoromethyl copper complex is 0.05~1 mmol / mL. Preferably, it is 0.1 mmol / mL.

[0017] In one embodiment of the invention, the addition cyclization reaction is carried out under an inert gas atmosphere. A nitrogen atmosphere is preferred.

[0018] The second objective of this invention is to provide a novel, green, and economical synthesis method, comprising the following steps: Using arylimine-type trifluoromethyl copper complex, o-alkenylarylurea compounds, potassium carbonate, and potassium persulfate as raw materials, the crude product of 4-trifluoroethyl-2-quinazolinone compounds was obtained after stirring and reacting under blue light irradiation at 25°C for a period of time. Then, pure 4-trifluoroethyl-2-quinazolinone compounds were obtained by extraction, filtration, washing, and column chromatography purification.

[0019] In one embodiment of the present invention, the method is preferably carried out as follows: arylimine trifluoromethyl copper complex, o-alkenylarylurea compound, potassium carbonate and potassium persulfate are added to a reaction vessel containing DMF solvent in a molar ratio of 1:1.5:1.2:2.0, stirred for 12 hours under blue light irradiation at 25°C, and then separated and purified to obtain the target product.

[0020] A third objective of this invention is to provide the application of the method in the fields of medicine and pesticides.

[0021] In one embodiment of the present invention, the application is used to prepare and modify functional groups to obtain quinazolinone compounds. According to patents such as CN 113754594 A, CN 120887838 A and CN 119462655 A, quinazolinone compounds have antitumor activity, anti-inflammatory activity or antidepressant activity, and therefore have potential drug activity and drug application prospects, and can be used in the research and development of anti-inflammatory, antibacterial, antitumor, antiviral and other drug fields.

[0022] Beneficial effects: (1) The method of the present invention uses pyridyl trifluoromethyl copper complex and aryl imine compounds as reactants in an air atmosphere to facilitate the rapid preparation of aryl imine trifluoromethyl copper complex, and obtain more stable and easier-to-store fluorinated hydrocarbon copper complex.

[0023] (2) The method of the present invention uses arylimine-type trifluoromethyl copper complex, o-alkenyl arylurea compound, potassium carbonate and potassium persulfate as reactants in a nitrogen atmosphere to realize the construction of the 4-trifluoroethyl-2-quinazolinone compound skeleton in a one-pot reaction to obtain the target product.

[0024] (3) The method of the present invention uses a novel trifluoromethyl copper complex as a fluorine source. The ligands in this complex have a larger conjugated structure and have the potential for photoreaction. Moreover, it can generate trifluoromethyl radicals by homolytic cleavage at room temperature with only blue light irradiation. It can be applied to reactions sensitive to high temperature. Therefore, the substrate has wide applicability, the raw materials are simple and easy to obtain, and the economic cost is low. In addition, the method of the present invention does not require a catalyst to achieve the synthesis of the target product and only requires 12 hours of reaction to obtain the target product in good yield. The method is fast and efficient.

[0025] (4) The synthesis method of the present invention converts readily available o-alkenylarylurea compounds into corresponding 2-quinazolinone compounds under relatively simple conditions, thereby achieving the synthesis of 4-trifluoroethyl-2-quinazolinone compounds in one step. The target compounds have wide applications in the fields of medicine, pesticides and functional materials. Attached Figure Description

[0026] Figure 1 This is a synthetic route diagram of the present invention; Figure 2 This is the X-ray single-crystal diffraction pattern of the arylimine-type trifluoromethyl copper complex in Example 1 of the present invention; Figure 3 This is the structural formula of the target product in Embodiment 12 of the present invention. Detailed Implementation

[0027] The preferred embodiments of the present invention are described below. It should be understood that the embodiments are for better explanation of the present invention and are not intended to limit the present invention.

[0028] The following are specific embodiments of the present invention.

[0029] 1. The o-alkenylarylurea compounds involved in the following examples, such as N-(2-vinylphenyl)-N′-(4-methylphenyl)urea; N-(2-vinyl-4-tert-butylphenyl)-N′-(4-methylphenyl)urea; N-(2-vinyl-4-nitrophenyl)-N′-(4-methylphenyl)urea; N-(2-vinyl-3-cyanophenyl)-N′-(4-methylphenyl)urea; N-(4,6-dimethyl-2-vinylphenyl)-N′-(4-methylphenyl)urea; and N-(2-vinyl-6-methoxyphenyl)-N′-(4-methylphenyl)urea, were synthesized by methods reported in existing literature.

[0030] Potassium carbonate, potassium persulfate N,N Dimethylformamide, ethyl acetate, and anhydrous MgSO4 were all purchased from Adamas.

[0031] 2. The chromatographic separation and purification method involved in the following examples: Column type: G3, stationary phase: silica gel (particle size 200-300 mesh), mobile phase: V石油醚 :V 乙酸乙酯 =10:1.

[0032] 3. The synthesis route diagram of the embodiments of the present invention, as follows: Figure 1 As shown, specifically: The pyridyl trifluoromethyl copper complex and the aryl imine compound were added to a reaction vessel containing dichloromethane solvent at a molar ratio of 1:1.5 and stirred at 25°C for 1 hour to obtain the aryl imine type trifluoromethyl copper complex.

[0033] Using arylimine-type trifluoromethyl copper complexes, o-alkenylarylurea compounds, potassium carbonate, and potassium persulfate as raw materials, a 4-trifluoroethyl-2-quinazolinone compound was obtained after stirring under blue light irradiation at 25°C for a period of time. The reaction formula is as follows: Figure 1 .

[0034] 4. Based on the solutions provided above, the technical solution of the present invention is further optimized to... Figure 1 4-Trifluoroethyl-2-quinazolinone compounds.

[0035] Example 1: Synthesis of arylimine-type trifluoromethylcopper complex

[0036] In an air atmosphere, pyridyl trifluoromethyl copper complex (871 mg, 2.5 mmol) and 2,6-[1-methyl-2-( N [-phenylimine]pyridine (826 mg, 3.75 mmol) and dichloromethane (10 mL) were added to a 50 mL reaction tube equipped with a stir bar and reacted at 25 °C and 400 rpm for 1 h. After the reaction was completed, the mixture was filtered, and the filter cake was washed with cold dichloromethane and then dried under vacuum to obtain 979 mg of the target compound, an arylimine-type trifluoromethyl copper complex, with a yield of 80%. After washing with dichloromethane, the purity can reach over 95%. Figure 2 ).

[0037] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, DMSO) δ 8.66 (s, 1H), 7.45 (t, J = 7.0 Hz, 2H), 7.23 (t, J = 7.4 Hz, 1H), 6.99 (d, J = 7.7 Hz, 3H), 2.53 (s, 2H). 19F NMR (376 MHz, DMSO) δ -24.00 – -24.28 (m), -33.23 (q, J = 9.2 Hz). Example 2: Synthesis of 3-(4-Tolyl)-4-trifluoroethyl-2-quinazolinone

[0038] Under nitrogen protection, the arylimine-type trifluoromethyl copper complex (48.9 mg, 0.1 mmol), N-(2-vinylphenyl)-N′-(4-tolyl)urea (37.8 mg, 0.15 mmol), potassium carbonate (16.6 mg, 0.12 mmol), potassium persulfate (54.1 mg, 0.2 mmol), and DMF (2 mL) synthesized in Example 1 were added to a 25 mL reaction tube equipped with a stir bar. The reaction tube was irradiated with 390 nm blue light and stirred at a distance of about 5 cm from the light source for 12 hours. After the reaction was completed, the mixture was extracted with ethyl acetate and deionized water. After thorough shaking, the mixture was allowed to stand for separation and separation. Anhydrous MgSO4 was added to the obtained organic phase for drying. The mixture was filtered, and the organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 24.3 mg of the target compound, with a yield of 80%.

[0039] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 7.8Hz, 1H), 7.14 (d, J = 8.0 Hz, 3H), 7.06 (t, J = 7.4 Hz, 1H), 6.99 (d, J = 7.5Hz, 1H), 5.65 (dd, J = 10.2, 3.0 Hz, 1H), 2.90 – 2.76 (m, 1H), 2.49 (t, J =12.4 Hz, 1H), 2.32 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -63.24. 13 C NMR (101 MHz, CDCl3) δ 148.60, 139.80, 134.48, 131.97, 128.67, 128.46, 125.70, 122.46 (d, J = 22.5 Hz), 122.06, 120.93, 118.88, 38.32, 38.04, 19.76. Example 3: Synthesis of 3-(4-Tolyl)-4-trifluoroethyl-6-tert-butyl-2-quinazolinone

[0040] Under nitrogen protection, the arylimine-type trifluoromethyl copper complex (48.9 mg, 0.1 mmol), N-(2-vinyl-4-tert-butylphenyl)-N′-(4-tolyl)urea (46.3 mg, 0.15 mmol), potassium carbonate (16.6 mg, 0.12 mmol), potassium persulfate (54.1 mg, 0.2 mmol), and DMF (2 ml) synthesized in Example 1 were added to a 25 mL reaction tube equipped with a stir bar. The mixture was irradiated with 390 nm blue light and stirred at a distance of approximately 5 cm from the light source for 12 hours. After the reaction was completed, the mixture was extracted with ethyl acetate and deionized water. After thorough shaking, the mixture was allowed to stand and separate into layers. Anhydrous MgSO4 was added to the obtained organic phase for drying. The mixture was filtered, and the organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 26.7 mg of the target compound, with a yield of 74%.

[0041] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 8.0 Hz, 2H), 7.31 (dd, J = 8.3, 2.2 Hz, 1H), 7.13 (d, J = 8.2 Hz, 2H), 7.07 (d, J = 8.3 Hz, 1H), 6.97 (s, 1H), 5.63 (dd, J = 10.1, 3.0 Hz, 1H), 2.89 – 2.76 (m, 1H), 2.47 (ddd, J = 15.6,10.8, 3.2 Hz, 1H), 2.32 (s, 3H), 1.31 (s, 9H). 19 F NMR (376 MHz, CDCl3) δ -63.17. Example 4: Synthesis of 3-(4-Tolyl)-4-trifluoroethyl-6-nitro-2-quinazolinone

[0042] Under nitrogen protection, the arylimine-type trifluoromethyl copper complex (48.9 mg, 0.1 mmol), N-(2-vinyl-4-nitrophenyl)-N′-(4-tolyl)urea (44.6 mg, 0.15 mmol), potassium carbonate (16.6 mg, 0.12 mmol), potassium persulfate (54.1 mg, 0.2 mmol), and DMF (2 ml) synthesized in Example 1 were added to a 25 mL reaction tube equipped with a stir bar. The reaction tube was irradiated with 390 nm blue light and stirred at a distance of about 5 cm from the light source for 12 hours. After the reaction was completed, the mixture was extracted with ethyl acetate and deionized water. After thorough shaking, the mixture was allowed to stand for separation and separation. Anhydrous MgSO4 was added to the obtained organic phase for drying. The mixture was filtered, and the organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 17.1 mg of the target compound, with a yield of 49%.

[0043] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 17.4Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.2 Hz, 2H), 5.36 (s, 1H), 2.35(s, 3H), 2.22 (t, J = 8.3 Hz, 1H), 2.03 (d, J = 10.0 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ -60.88. Example 5: Synthesis of 3-(4-Tolyl)-4-trifluoroethyl-7-cyano-2-quinazolinone

[0044] Under nitrogen protection, the arylimine-type trifluoromethyl copper complex (48.9 mg, 0.1 mmol), N-(2-vinyl-5-cyanophenyl)-N′-(4-tolyl)urea (41.6 mg, 0.15 mmol), potassium carbonate (16.6 mg, 0.12 mmol), potassium persulfate (54.1 mg, 0.2 mmol), and DMF (2 ml) synthesized in Example 1 were added to a 25 mL reaction tube equipped with a stir bar. The reaction tube was irradiated with 390 nm blue light and stirred at a distance of about 5 cm from the light source for 12 hours. After the reaction was completed, the mixture was extracted with ethyl acetate and deionized water. After thorough shaking, the mixture was allowed to stand for separation and separation. Anhydrous MgSO4 was added to the obtained organic phase for drying. The mixture was filtered, and the organic phases were combined and the solvent was removed by vacuum distillation. The crude product was then purified by column chromatography to obtain 7.6 mg of the target compound, with a yield of 23%.

[0045] The obtained product was analyzed and characterized, and the specific data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.91 (d, J = 8.3 Hz, 1H), 7.35 (d, J = 15.8Hz, 2H), 7.20 (d, J = 11.1 Hz, 2H), 6.71 (s, 1H), 6.39 (s, 1H), 5.35 (t, J =4.8 Hz, 1H), 2.35 (s, 3H), 2.27 – 2.21 (m, 1H), 2.01 (d, J = 6.4 Hz, 1H). 19 FNMR (376 MHz, CDCl3) δ -60.88. Example 6: Effects of different bases on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone Referring to Example 2, the base was replaced with sodium bicarbonate (16.6 mg, 0.198 mmol), sodium hydroxide (16.6 mg, 0.415 mmol), potassium tert-butoxide (16.6 mg, 0.148 mmol), and sodium carbonate (16.6 mg, 0.157 mmol) respectively, while keeping other conditions unchanged, to synthesize 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone. Specific yield results are shown in Table 1.

[0046] Table 1. Effects of different inorganic bases on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone

[0047] The results showed that using sodium bicarbonate, sodium hydroxide, potassium tert-butoxide, or sodium carbonate instead of potassium carbonate in Example 2 as the base could all yield the target product, but the product yield was worse than that in Example 1.

[0048] Example 7: Effect of different solvents on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone Referring to Example 2, the solvent was changed from... N,N By replacing dimethylformamide with acetonitrile (CH3CN), dichloromethane (DCM), and tetrahydrofuran (THF), respectively, under the same conditions, 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone was synthesized. Specific yield results are shown in Table 2.

[0049] Table 2. Effects of different solvents on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone

[0050] The results showed that replacing acetonitrile, dichloromethane, and tetrahydrofuran in Example 2 was effective. N,N Using dimethylformamide as a solvent, the target product can be obtained, but the product yield is worse than that in Example 2.

[0051] Example 8: Effect of different oxidants on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone Referring to Example 2, the oxidant was replaced by potassium persulfate instead of [other oxidant]. N 3-(4-Tolyl)-4-trifluoroethyl-2-quinazolinone was synthesized using fluorobis(benzenesulfonamide) (NFSI, 54.1 mg, 0.172 mmol), sodium persulfate (54.1 mg, 0.227 mmol), and cerium ammonium nitrate (CAN, 54.1 mg, 0.0987 mmol) under otherwise constant conditions. Specific yield results are shown in Table 3.

[0052] The specific yield results are shown in Table 3.

[0053] Table 3. Effects of different oxidants on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone

[0054] The results showed that: using N Replacing potassium persulfate in Example 2 with fluorobisbenzenesulfonamide (NFSI), sodium persulfate, or cerium ammonium nitrate (CAN) also yielded the target product, but the product yield was worse than that in Example 2.

[0055] Example 9: Effect of different wavelengths of blue light on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone Referring to Example 2, while ensuring the irradiation distance was 5 cm, the blue light wavelength of 390 nm was replaced with 365 nm, and other conditions remained unchanged, to synthesize 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone. The specific yield results are shown in Table 4.

[0056] Table 4. Effects of blue light at different wavelengths on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone

[0057] The results showed that replacing 390nm in Example 2 with 365nm could yield the target product, but the product yield was worse than that in Example 2.

[0058] Example 10: Molar ratios of different trifluoromethylcopper reagents, o-alkenylarylurea compounds, oxidants, and bases Referring to Example 2, the molar ratios of the arylimine-type trifluoromethyl copper complex, o-alkenylarylurea compound, oxidant, and base synthesized in Example 1 were adjusted to 1:1.5:1.5:1.2, 1:1.5:2:2, 1:1.5:2:3, and 1:1:2:1.2, while keeping other conditions unchanged, to synthesize 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone. Specific yield results are shown in Table 5.

[0059] Table 5. Effects of the molar ratios of arylimine-type trifluoromethyl copper complexes, o-alkenylarylurea compounds, oxidants, and bases synthesized in Example 1 on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone

[0060] The results showed that replacing the 1:1.5:2:1.2 ratio in Example 2 with the arylimine-type trifluoromethyl copper complex synthesized in Example 1, the o-alkenylarylurea compound, the oxidant, and the base in the molar ratios of 1:1.5:1.5:1.2, 1:1.5:2:2, 1:1.5:2:3, and 1:1:2:1.2, all yielded the target product, but the yield of the product was worse than that in Example 2.

[0061] Example 11: Different reaction times Referring to Example 2, the reaction time of blue light irradiation was adjusted to 8 h, 10 h, 18 h, and 24 h, while other conditions remained unchanged, to synthesize 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone. Specific yield results are shown in Table 7.

[0062] Table 7. Effect of different reaction times on the synthesis of 3-(4-tolyl)-4-trifluoroethyl-2-quinazolinone

[0063] The results showed that replacing the 12 h reaction time in Example 2 with 8 h, 10 h, 18 h, and 24 h all yielded the target product, but the product yield was worse than that in Example 2, and there was no significant change in the reaction yield when the reaction time was extended.

[0064] Example 12: The synthesis route diagram of this embodiment is as follows: Figure 1 As shown, adjust R 1 and R 2 , structural formula as Figure 3 As shown. Specifically: Table 8

[0065] The obtained product was analyzed and characterized, and the specific data are as follows: Option (1): 1 H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 8.2 Hz, 2H), 7.13 (d, J = 9.4Hz, 2H), 7.05 (d, J = 8.1 Hz, 1H), 6.83 – 6.77 (m, 1H), 5.61 (dd, J = 10.2,2.8 Hz, 1H), 2.83 (s, 1H), 2.47 (ddd, J = 15.6, 10.9, 2.9 Hz, 1H), 2.32 (s,6H). 19 F NMR (376 MHz, CDCl3) δ -63.26. Option (2): 1 H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 7.9 Hz,2H), 7.00 (s, 1H), 6.64 (s, 1H), 5.55 (d, J = 10.2 Hz, 1H), 2.88 – 2.74 (m,2H), 2.40 (s, 3H), 2.33 (s, 3H), 2.29 (s, 3H). 1919F NMR (376 MHz, CDCl3) δ -63.29. Scheme (3): 1 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J J = 8.2 Hz, 2H), 7.14 (d, J J = 7.9 Hz,1H), 6.88 (d, J J = 8.3 Hz, 1H), 6.68 (d, J J = 2.5 Hz, 1H), 6.61 (dd, J J = 8.3, 2.5Hz, 1H), 5.61 (dd, J J = 10.0, 3.0 Hz, 1H), 3.80 (s, 3H), 2.79 (dt, J J = 15.6, 9.9Hz, 1H), 2.55 – 2.38 (m, 1H), 2.33 (s, 3H). 19 19F NMR (376 MHz, CDCl3) δ -63.21. Scheme (4): 1 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J J = 7.9 Hz, 2H), 7.19 – 7.07 (m,3H), 6.85 (dd, J J = 8.7, 2.9 Hz, 1H), 6.55 (s, 1H), 5.61 (d, J J = 7.5 Hz, 1H),3.80 (s, 3H), 2.89 – 2.76 (m, 2H), 2.32 (s,3H). 19 19F NMR (376 MHz, CDCl3) δ -63.21. Scheme (5): 1 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J J = 8.0 Hz, 2H), 7.13 (d, J J = 8.1 Hz,2H), 7.04 (t, J J = 7.9 Hz, 1H), 6.89 (d, J J = 8.2 Hz, 1H), 6.63 (d,J = 7.7 Hz, 1H), 5.68 (d, J = 9.5 Hz, 1H), 3.94 (s, 3H), 2.91 – 2.74 (m, 0H), 2.62 – 2.46 (m, 2H), 2.32 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -63.31. Option (6): 1 H NMR (400 MHz, CDCl3) δ 11.27 (s, 1H), 8.52 (dd, J = 12.4, 2.6 Hz,1H), 7.77 – 7.69 (m, 1H), 7.31 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.2 Hz, 3H), 5.35 (t, J = 4.8 Hz, 1H), 2.34 (s, 3H), 2.31 – 2.18 (m, 1H), 2.01 (d, J = 6.1Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ -62.00, -96.93. Option (7): 1 H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.0 Hz, 3H), 7.03 (dd, J = 8.1, 2.1 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H), 5.62 (dd, J =10.0, 3.1 Hz, 1H), 2.81 (dt, J = 15.5, 9.8 Hz, 1H), 2.46 (ddd, J = 15.6, 10.7,3.2 Hz, 1H), 2.33 (s, 3H). 19 F NMR (376 MHz, CDCl3) δ -63.16. Option (8): 1 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J J = 7.7 Hz, 1H), 7.44 (d, J J = 8.1 Hz,2H), 7.25 – 7.18 (m, 2H), 7.16 (d, J J = 8.1 Hz, 2H), 5.69 (dd, J J = 10.1, 3.0 Hz,1H), 2.92 – 2.76 (m, 1H), 2.59 – 2.43 (m, 1H), 2.34 (s,3H). 19 19F NMR (376 MHz,CDCl3) δ -61.80, -63.16. Scheme (9): 1 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J J = 9.0 Hz, 2H), 7.32 – 7.24 (m,1H), 7.11 (d, J J = 7.9 Hz, 1H), 7.04 (t, J J = 7.4 Hz, 1H), 6.97 (d, J J = 7.8 Hz,2H), 5.63 (dd, J J = 10.0, 3.0 Hz, 1H), 3.80 (s, 3H), 2.82 (dp, J J = 17.0, 9.9 Hz,1H), 2.57 – 2.39 (m, 1H). 19 19F NMR (376 MHz, CDCl3) δ -63.25. Scheme (10): 1 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J J = 8.8 Hz,2H), 7.70 (d, J J = 8.5 Hz,2H), 7.33 (t, J J = 7.7 Hz, 1H), 7.19 (d, J J = 7.9 Hz, 1H), 7.12 (t, J J = 7.4 Hz,1H), 7.02 (d, J= 7.5 Hz, 1H), 5.71 (dd, J = 10.2, 2.9 Hz, 1H), 2.98 – 2.75 (m,1H), 2.59 (s, 3H), 2.55 – 2.45 (m, 1H). 19 19F NMR (376 MHz, CDCl3) δ -63.21. Scheme (11): 1 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.8 Hz, 2H), 7.72 (d, J = 8.8 Hz,2H), 7.45 (td, J = 7.7, 1.5 Hz, 1H), 7.16 (d, J = 7.9 Hz, 1H), 7.08 (td, J =7.5, 1.1 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 5.73 (dd, J = 10.1, 2.9 Hz, 1H),2.53 – 2.47 (m, 1H), 2.03 (q, J = 6.6 Hz,1H). 19 19F NMR (376 MHz, CDCl3) δ -63.22. Scheme (12): 1 1H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 8.8 Hz,2H), 7.35 (td, J = 7.7, 1.5 Hz, 1H), 7.20 (d, J = 7.9 Hz, 1H), 7.15 (td, J =7.5, 1.1 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H), 5.75 (dd, J = 10.1, 2.9 Hz, 1H),2.63 – 2.46 (m, 1H), 2.01 (q, J = 6.6 Hz,1H). 19F NMR (376 MHz, CDCl3) δ -63.24. Scheme (13): Option (13): 1 H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.4 Hz, 2H), 7.31 (dd, J = 7.7, 5.4 Hz, 3H), 7.17 (d, J = 7.9 Hz, 1H), 7.11 (t, J = 7.5 Hz, 1H), 7.01 (d, J =7.6 Hz, 1H), 5.70 (dd, J = 10.1, 2.9 Hz, 1H), 2.93 – 2.75 (m, 1H), 2.53 (ddd, J = 15.0, 10.6, 3.1 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ -63.26. Scheme (14): Option (14): 1 H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 5.69 (dd, J = 10.1, 3.0 Hz, 1H), 2.92 – 2.74 (m,1H), 2.52 (ddd, J = 15.6, 10.7, 3.1 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ -63.25. Option (15): 1 H NMR (400 MHz, CDCl3) δ 7.45 (q, J= 9.0 Hz, 4H), 7.31 (t, J = 7.7 Hz, 1H), 7.14 (d, J = 7.9 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 7.4 Hz, 1H), 5.66 (dd, J = 10.1, 3.0 Hz, 1H), 2.92 – 2.73 (m, 1H), 2.50 (ddd, J = 15.7, 10.7, 3.0 Hz, 1H). 19 F NMR (376 MHz, CDCl3) δ -63.24. Comparative Example 1: Referring to Example 2, potassium carbonate was not added, and everything else remained the same.

[0066] The results showed that without the addition of potassium carbonate, the yield decreased to 26%.

[0067] Comparative Example 2: Referring to Example 2, potassium persulfate was not added, and everything else remained the same.

[0068] The results showed that without the addition of potassium persulfate, the yield decreased to 35%.

[0069] Comparative Example 3: Referring to Example 2, the free radical scavenger TEMPO was added, while everything else remained the same.

[0070] The results showed that adding TEMPO reduced the yield to 7%.

[0071] Comparative Example 4: Referring to Example 2, the reported pyridyltrifluoromethylcopper complex was used as a control, and the reaction was carried out under the same conditions. The results showed that the yield of the control group was 0%.

[0072] Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Anyone skilled in the art can make various modifications and alterations without departing from the spirit and scope of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for synthesizing a 4-trifluoroethyl-2-quinazolinone compound, characterized in that, The structure of the compound is as follows: The method involves using an o-alkenylarylurea compound of formula (1) and a novel trifluoromethyl copper complex as trifluoromethylating agents in an organic solvent to undergo an addition cyclization reaction, thereby synthesizing a trifluoromethylated quinazolinone compound of formula (2): ， Among them, R 1 Selected from H, C1 alkyl, halogen, cyano, nitro, C1 alkoxy, ester; R 2 Selected from C1 alkyl, C1 alkoxy, halogen, nitro, cyano, and acyl groups; The pyridyltrifluoromethylcopper complex, 2,6-[1-methyl-2-( N A novel trifluoromethyl copper complex was synthesized using pyridine (-benzylamine) as a reactant and dichloromethane as a solvent.

2. The method according to claim 1, characterized in that, The organic solvent includes N,N - Any one or more of dimethylformamide, acetonitrile, dichloromethane, and tetrahydrofuran.

3. The method according to claim 1, characterized in that, The oxidant includes potassium persulfate, N - Any one or more of fluorobisbenzenesulfonamide, sodium persulfate, and cerium ammonium nitrate.

4. The method according to claim 1, characterized in that, The alkali includes any one or more of potassium carbonate, sodium bicarbonate, sodium hydroxide, potassium tert-butoxide, and sodium carbonate.

5. The method according to claim 1, characterized in that, The blue light wavelength is either 365nm or 390nm; optionally, the synthesis reaction is carried out at a distance of 3 to 10 cm from the blue light.

6. The method according to claim 1, characterized in that, The reaction temperature is 25 ℃-50 ℃.

7. The method according to claim 1, characterized in that, The molar ratio of the novel trifluoromethyl copper complex, the o-alkenylarylurea compound, the oxidant and the base is 1:(1.0-2.0):(1.0-2.0):(1.0-2.0).

8. The method according to claim 1, characterized in that, The reaction concentration of the novel trifluoromethyl copper complex is 0.05-1 mmol / mL.

9. The method according to claim 1, characterized in that, The addition cyclization reaction was carried out in an inert gas atmosphere.

10. The application of the method according to any one of claims 1-9 in the fields of pharmaceutical and pesticide preparation.

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