A bistrifluoromethyl-containing coumarin tertiary alcohol compound, a preparation method and application thereof

Abstract

The application provides a coumarin tertiary alcohol compound containing bistrifluoromethyl and a preparation method and application thereof, and belongs to the technical field of organic synthesis chemistry, and aims to solve the technical problems of single structure and poor bactericidal activity of existing trifluoro tertiary alcohol compounds.The structural formula of the coumarin tertiary alcohol compound is shown in the following formula: in the formula, R is Me, OMe, OEt, F, Cl, Br or Ph.The preparation method is as follows: a trifluoroacetyl coumarin compound, a trifluoromethyl silane compound, a catalyst and a solvent are mixed to prepare a reaction solution, the reaction solution is fully reacted, and after purification, the coumarin tertiary alcohol compound is prepared.The application widens the synthesis of bistrifluoromethyl tertiary alcohol and tertiary alcohol siloxane compound products, the compound has excellent antibacterial activity, has a good effect on more plant fungal diseases, is worth further exploration, and has a wide exploration and application space in the field of pesticides.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis chemistry, and particularly relates to a fluorine-containing coumarin tertiary alcohol and a derivative thereof. BACKGROUND

[0002] Compounds containing trifluoromethyl (CF3) have very wide applications in biology, pharmacy, agriculture, organic materials and other fields, mainly because the introduction of trifluoromethyl can significantly improve the lipophilicity and metabolic stability of the compound. Its performance is excellent, and it has a wide range of uses. Trifluoromethylation is an effective means of introducing trifluoromethyl into target compounds. The introduction of fluorine-containing groups or fluorine atoms in polymers can significantly improve the thermal stability, hydrophobicity / oil repellency, chemical corrosion resistance, oxidation resistance and insulation of the polymers, and therefore fluorine-containing organic compounds are widely used in medicine, pesticides, functional materials and dyes. According to statistical data, 30% of pesticides and 20% of medicines currently contain fluorine atoms. The following are several fluorine-containing pesticides:

[0003] Compound A is a very useful fluorine-containing intermediate, which is widely used in the fields of pesticides, medicines, veterinary drugs, etc. It can be used as a raw material to produce herbicide fluazifop-P-butyl, insecticide chlorfluazuron, pymetrozine, etc. Compound B is an insecticide disclosed in 2017, which has good control effect on Spodoptera litura, Trichoplusia ni and Aedes. Compound C is flubendiamide, which is a neonicotinoid insecticide acting on the acetylcholine receptor of insects. It is mainly used for controlling piercing-sucking mouthpart pests of vegetables, fruit trees and field crops. Compound D is an insecticide, which has good insecticidal effect on Myzus persicae, brown planthopper and the like. Compound E is an SDHI fungicide, which has good effect on powdery mildew, gray mold and the like. Compound F is a triazole fungicide, which can be applied to corn, soybean, grain and other crops, and has the effects of control and protection on crops.

[0004] Coumarin is a natural product, widely distributed in the plants of Rutaceae, Umbelliferae, Leguminosae, Compositae and Orchidaceae. Coumarin derivatives are widely concerned due to their diverse structures, multiple activities and low toxicity. They have a wide range of applications in the fields of medicine, bioactive antifungal drugs, etc. Introducing trifluoromethyl group on coumarin ketone structure is a common organic chemical synthesis strategy, which is often used to prepare compounds with specific biological activity. Obtaining coumarin tertiary alcohol compounds and introducing trifluoromethyl group on them need to selectively introduce one trifluoromethyl group to a specific position of coumarin tertiary alcohol. However, when introducing fluorine-containing groups on coumarin compounds, the existing synthesis methods may have the following shortcomings: such as reaction complexity, the introduction of fluorine-containing groups may require a complex multi-step reaction sequence, including oxidation, reduction, halogenation and fluorination steps, and in the process of introducing fluorine-containing groups, the final yield may be low due to side reactions or other chemical factors. Although there are some methods for synthesizing coumarin compounds and introducing fluorine-containing groups, there may still be problems such as unsatisfactory synthesis path, harsh reaction conditions or long time. In addition, although many experimental data prove that trifluoro tertiary alcohol compounds have good biological activity, the bactericidal activity still needs to be further improved. SUMMARY

[0005] In order to solve the above technical problems, the present application provides a coumarin tertiary alcohol compound containing double trifluoromethyl groups, a preparation method and application thereof, which widens the synthesis of double trifluoromethyl tertiary alcohol and tertiary alcohol siloxane compounds, and the compound has excellent antibacterial activity and good effect on many plant fungal diseases, which is worthy of further exploration and has a wide exploration and application space in the field of pesticides.

[0006] In order to achieve the above purpose, the technical scheme of the present application is as follows:

[0007] A coumarin tertiary alcohol compound containing double trifluoromethyl groups, the structural formula of the coumarin tertiary alcohol compound is as follows:

[0008] In the formula, R is Me, OEt, OMe, F, Cl, Br or Ph.

[0009] A coumarin tertiary alcohol compound containing double trifluoromethyl groups, comprising the following steps: mixing trifluoroacetyl coumarin compound, trifluoromethyl silane compound, catalyst and solvent to prepare a reaction solution, and fully reacting to obtain the coumarin tertiary alcohol compound after purification.

[0010] The structural formula of the trifluoroacetyl coumarin compound is as follows:

[0011] In the formula, R is Me, OEt, OMe, F, Cl, Br or Ph.

[0012] The catalyst is cesium fluoride (CsF), cesium acetate (CsOAc), cesium carbonate (Cs2CO3) and the like, and the catalyst is used in an amount of 20-100 mol%.

[0013] The solvent is tetrahydrofuran (THF), N,N-dimethylformamide (DMF), acetonitrile (MeCN) and the like.

[0014] The solvent is super dry solvent (water content less than 50 ppm), and the super dry solvent is super dry tetrahydrofuran.

[0015] The molar ratio of the trifluoroacetyl coumarin compound and the trifluoromethyl silane compound is 1: (1-3) mmol / mL.

[0016] The catalyst is used in an amount of 20-100 mol%.

[0017] The concentration of the trifluoroacetyl coumarin compound in the reaction solution is (0.25-1).

[0018] The reaction temperature is 50-120 DEG C, and the reaction time is 5-12 h.

[0019] Application of a coumarin tertiary alcohol compound containing double trifluoromethyl in the field of agricultural antibacterial fungicides.

[0020] The application has the beneficial effects that the coumarin ketone compound and the trifluoromethyl silane compound which are commercially available are selected as reactants, the synthesis of the double trifluoromethyl coumarin tertiary alcohol is realized under the action of a catalyst, and it is verified that the double trifluoromethyl coumarin tertiary alcohol indeed has good and broad-spectrum fungicidal activity.

[0021] The application realizes the construction of the skeleton of the novel double trifluoromethyl coumarin tertiary alcohol and tertiary alcohol siloxane compound, provides a simple and effective synthesis method for the construction of the skeleton, and the method has the characteristics of mild reaction condition, simple operation, economical step, strong functional group tolerance and good yield, etc. BRIEF DESCRIPTION OF DRAWINGS

[0022] In order to more clearly illustrate the technical solutions of the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or prior art description will be briefly introduced. Obviously, the drawings in the following description only constitute some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative effort on the basis of these drawings.

[0023] Figure 1 The figure is a nuclear magnetic spectrum of compound 3a, (a) is a nuclear magnetic 1 H spectrum; (b) is a nuclear magnetic 13 C spectrum; (c) is a nuclear magnetic 19 F spectrum.

[0024] Figure 2 The figure is a nuclear magnetic spectrum of compound 3b, (a) is a nuclear magnetic 1 H spectrum; (b) is a nuclear magnetic 13 C spectrum; (c) is a nuclear magnetic 19 F spectrum.

[0025] Figure 3 The figure is a nuclear magnetic spectrum of compound 3c, (a) is a nuclear magnetic 1 H spectrum; (b) is a nuclear magnetic 13 C spectrum; (c) is a nuclear magnetic 19 F spectrum.

[0026] Figure 4 The figure is a nuclear magnetic spectrum of compound 3d, (a) is a nuclear magnetic 1 H spectrum; (b) is a nuclear magnetic 13 C spectrum; (c) is a nuclear magnetic 19 F spectrum.

[0027] Figure 5 The figure is a nuclear magnetic spectrum of compound 3e, (a) is a nuclear magnetic 1 H spectrum; (b) is a nuclear magnetic 13 C spectrum; (c) is a nuclear magnetic 19 F spectrum.

[0028] Figure 6 The figure is a nuclear magnetic spectrum of compound 3f, (a) is a nuclear magnetic 1 H spectrum; (b) is a nuclear magnetic 13 C spectrum; (c) is a nuclear magnetic 19 F spectrum.

[0029] Figure 7 The figure is a nuclear magnetic spectrum of compound 3g, (a) is a nuclear magnetic 1 H spectrum; (b) is a nuclear magnetic 13 C spectrum; (c) is a nuclear magnetic 19 F spectrum.

[0030] Figure 8 NMR spectra of compound 3h, (a) is the1H NMR spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 1 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 13 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 19 F spectrum.

[0031] Figure 9 NMR spectra of compound 3i, (a) is the1H NMR spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 1 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 13 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 19 F spectrum.

[0032] Figure 10 NMR spectra of compound 3j, (a) is the1H NMR spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 1 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 13 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 19 F spectrum.

[0033] Figure 11 NMR spectra of compound 3k, (a) is the1H NMR spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 1 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 13 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 19 F spectrum.

[0034] Figure 12 NMR spectra of compound 3l, (a) is the1H NMR spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 1 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 13 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 19 F spectrum.

[0035] Figure 13 NMR spectra of compound 3m, (a) is the1H NMR spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 1 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 13 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 19 F spectrum.

[0036] Figure 14 NMR spectra of compound 3n, (a) is the1H NMR spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 1 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 13 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 19 F spectrum.

[0037] Figure 15 NMR spectra of compound 3o, (a) is the1H NMR spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 1 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 13 H spectrum; (b) is the13C NMR spectrum; (c) is the19F NMR spectrum. 19 F spectrum.

[0038] Figure 16The inhibition rate of 15 compounds on Sclerotinia sclerotiorum at 100 ppm.

[0039] Figure 17 The inhibition rate of 15 compounds on Botrytis cinerea at 100 ppm.

[0040] Figure 18 The inhibition rate of 15 compounds on Gaeumannomyces graminis at 100 ppm.

[0041] Figure 19 The inhibition rate of 15 compounds on Septoria tritici at 200 ppm.

[0042] Figure 20 The inhibition rate of 15 compounds on Fusarium oxysporum at 100 ppm.

[0043] Figure 21 The inhibition rate of 15 compounds on Fusarium moniliforme at 100 ppm. DETAILED DESCRIPTION

[0044] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the protection scope of the present application.

[0045] Embodiment 1

[0046]

[0047] Substituted fluorine-containing benzopyrone 1a (1.0 mmol), trifluoromethyl silane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added to a 10 mL reaction bottle, and reacted overnight in a 60-degree reaction module. The obtained reaction liquid was poured into a round-bottom flask, rotary evaporated until a small amount of liquid was left, an appropriate amount of silica gel was added, and rotary evaporation was continued until all the products were loaded onto the silica gel. The product was separated by silica gel column chromatography, and the target product (3a) was obtained. The eluent used was petroleum ether and ethyl acetate prepared in a ratio of 20:1. The product data characterization: (PE:EA=20:1, Rf=0.36, light yellow solid, 72% yield). The nuclear magnetic resonance results of compound 3a are shown in f Figure 1 1 ​​H NMR (400 MHz, Chloroform-d) δ 8.49 (s, 1H), 8.18 (s, 1H), 7.77-7.70 (m, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.45 (t, J = 8.2 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 145.80, 145.78, 145.75, 145.73, 145.70, 134.55, 129.63, 126.01, 122.21 (q, J = 288.6 Hz), 116.83, 79.94-75.30 (m). 19 F NMR (377 MHz, Chloroform-d) δ -76.12.

[0048] Example 2

[0049]

[0050] Under air atmosphere, 5-fluoro-3-trifluoromethylbenzopyrone 1b (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a 90 degree reaction module overnight. The resulting reaction solution was poured into a round bottom flask, and rotary evaporation was carried out until a small amount of liquid was left. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the eluent used was petroleum ether and ethyl acetate prepared in a ratio of 20: 1. The product data characterization: (PE: EA = 10: 1, Rf = 0.45, white solid, 52% yield). The nuclear magnetic resonance results of compound 3b are shown in f Figure 2 1 H NMR (400 MHz, Chloroform-d) δ 8.32 (s, 1H), 8.16 (s, 1H), 7.68-7.56 (m, 1H), 7.19 (d, J = 8.5 Hz, 1H), 7.09 (t, J = 8.6 Hz, 1H). 13 CNMR (101 MHz, CDCl3) δ 161.63, 158.98 (d, J = 259.5 Hz), 153.35 (d, J = 4.1 Hz), 138.64, 135.11 (d, J = 9.8 Hz), 122.22 (q, J = 289.1, 287.9 Hz), 114.91, 112.72 (d, J = 4.1 Hz), 111.78 (d, J = 19.5 Hz), 108.38 (d, J = 18.7 Hz), 77.94-75.80 (m). 19 ​​F NMR (377 MHz, CDCb) d -75.99, -116.64.

[0051] Example 3

[0052]

[0053] Into a 10 mL reaction vial, 5-chloro-3-trifluoromethylbenzopyrone 1c (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added under air atmosphere, and the reaction was carried out in a 60-degree reaction module for 5 hours. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was performed until a small amount of liquid remained. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the target product (3c) was obtained. The eluent used was petroleum ether and ethyl acetate prepared in a ratio of 10:1. Product data characterization: (PE:EA = 10:1, Rf = 0.47, green solid, 61% yield). The nuclear magnetic resonance results of compound 3c are shown in Figure 3 1 H NMR (400 MHz, Chloroform-d) d 8.57 (s, 1H), 8.24 (s, 1H), 7.64 (t, J = 8.2 Hz, 1H), 7.48 (dd, J = 8.0, 1.1 Hz, 1H), 7.36 (d, J = 8.5 Hz, 1H). 13 C NMR (101 MHz, CDCb) d 161.60, 153.82, 142.07, 142.04, 142.02, 141.99, 141.96, 134.46, 133.99, 126.53, 122.21 (q, J = 288.6 Hz), 116.49, 115.66, 115.46, 78.35 - 76.68 (m). 19 F NMR (377 MHz, CDCb) d -76.03.

[0054] Example 4

[0055]

[0056] ​Under air atmosphere, 5,7-dimethoxy-3-trifluoromethylbenzopyrone 1d (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a 100 degree reaction module overnight. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was performed until a small amount of liquid remained. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the target product (3d) was obtained. The eluent used was petroleum ether and ethyl acetate prepared in a ratio of 50:1. Product data characterization: (PE:EA = 50:1, Rf = 0.38, white solid, 44% yield). The nuclear magnetic results of compound 3d are shown in f Figure 4 1 H NMR (400 MHz, CDC13) δ 8.55 (s, 1H), 8.41 (s, 1H), 6.48 (s, 1H), 6.36 (s, 1H), 3.95 (s, 3H), 3.91 (s, 3H). 13 C NMR (101 MHz, CDC13) δ 166.18, 163.22, 157.98, 156.14, 140.85, 122.53 (q, J = 288.1 Hz), 107.94, 103.69, 96.02, 92.44, 77.85-76.21 (m), 56.33, 56.21. 19 F NMR (377 MHz, Chloroform-d) δ -76.35.

[0057] Example 5

[0058]

[0059] Under air atmosphere, 5,7-dimethoxy-3-trifluoromethylbenzopyrone 1d (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a 100 degree reaction module overnight. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was performed until a small amount of liquid remained. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the target product (3d) was obtained. The eluent used was petroleum ether and ethyl acetate prepared in a ratio of 50:1. Product data characterization: (PE:EA = 50:1, Rf = 0.38, white solid, 44% yield). The nuclear magnetic results of compound 3d are shown in f Figure 5 1 ​​​​H NMR (400 MHz, Chloroform-d) δ 8.28 (s, 1H), 8.11 (s, 1H), 7.67 (d, J = 10.5 Hz, 2H), 7.40 (d, J = 7.4 Hz, 1H). 13 CNMR (101 MHz, CDC13) δ 161.92, 159.38 (d, J = 247.7 Hz), 149.30, 144.67 (q, J = 3.0 Hz), 123.67, 122.19 (q, J = 24.7 Hz), 118.68 (d, J = 8.6 Hz), 118.44 (d, J = 9.3 Hz), 115.89, 114.72 (d, J = 24.5 Hz), 78.96 - 75.00 (m). 19 F NMR (377 MHz, Chloroform-d) δ -75.98, -114.37.

[0060] Example 6

[0061]

[0062] Under air atmosphere, 6-chloro-3-trifluoromethylbenzopyrone 1f (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a 60-degree reaction module overnight. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was carried out until a small amount of liquid was left. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the eluent used was petroleum ether and ethyl acetate prepared in a ratio of 10:1. The product data characterization: (PE:EA = 10:1, Rf = 0.42, green solid, 72% yield). The nuclear magnetic resonance results of compound 3f are shown in f Figure 6 1 H NMR (400 MHz, Chloroform-d) δ 8.28 (s, 1H), 8.11 (s, 1H), 7.67 (d, J = 10.5 Hz, 2H), 7.40 (d, J = 7.4 Hz, 1H). 13 CNMR (101 MHz, CDC13) δ 161.92, 159.38 (d, J = 247.7 Hz), 149.30, 144.67 (q, J = 3.0 Hz), 123.67, 122.19 (q, J = 24.7 Hz), 118.68 (d, J = 8.6 Hz), 118.44 (d, J = 9.3 Hz), 115.89, 114.72 (d, J = 24.5 Hz), 78.96 - 75.00 (m). 19 ​​F NMR (377 MHz, Chloroform-d) δ -76.01.

[0063] Example 7

[0064]

[0065] Under air atmosphere, 6-chloro-3-trifluoroformylbenzopyrone lg (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a 60 degree reaction module overnight. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was carried out until a small amount of liquid was left. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the target product (3g) was obtained. The eluent used was petroleum ether and ethyl acetate prepared in a ratio of 20: 1. Product data characterization: (PE: EA = 20: 1, R f = 0.53, brown solid, 41% yield). The nuclear magnetic resonance results of compound 3g are shown in Figure 7 1 H NMR (400 MHz, CDC13) δ 8.26 (s, 1H), 8.10 (s, 1H), 7.83 (s, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H). 13 CNMR (101 MHz, CDC13) δ 161.71, 151.90, 144.46, 137.24, 131.81, 122.22 (q, J = 288.7 Hz), 119.16, 118.69, 118.53, 115.79, 78.50-76.36 (m). 19 F NMR (377 MHz, CDC13) δ -76.01.

[0066] Example 8

[0067]

[0068] ​Under air atmosphere, 6-methyl-3-trifluoromethylbenzopyrone 1h (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a 60 degree reaction module overnight. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was performed until a small amount of liquid remained. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the target product (3h) was obtained. The eluent used was petroleum ether and ethyl acetate prepared in a ratio of 10:1. Product data characterization: (PE:EA = 10:1, Rf = 0.65, yellow solid, 77% yield). The nuclear magnetic results of compound 3h are shown in f Figure 8 1 H NMR (400 MHz, Chloroform-d) δ 8.56 (s, 1H), 8.12 (s, 1H), 7.52 (d, J = 8.5 Hz, 1H), 7.46 (s, 1H), 7.33 (d, J = 8.5 Hz, 1H), 2.46 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 162.66, 151.31, 145.67, 136.04, 135.62, 129.26, 122.40 (d, J = 288.7 Hz), 117.62, 116.55, 114.21, 122.40 (d, J = 288.7 Hz), 20.77. 19 F NMR (377 MHz, Chloroform-d) δ -76.13.

[0069] Example 9

[0070]

[0071] Under air atmosphere, 6-methyl-3-trifluoromethylbenzopyrone 1h (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a 60 degree reaction module overnight. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was performed until a small amount of liquid remained. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the target product (3h) was obtained. The eluent used was petroleum ether and ethyl acetate prepared in a ratio of 10:1. Product data characterization: (PE:EA = 10:1, Rf = 0.65, yellow solid, 77% yield). The nuclear magnetic results of compound 3h are shown in f Figure 9 1 ​​​​H NMR (400 MHz, DMSO-d6) δ 9.27 (s, 1H), 9.19 (s, 1H), 8.50 (d, J = 8.5 Hz, 1H), 8.32 (d, J = 9.1 Hz, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.81 (t, J = 7.7 Hz, 1H), 7.70 - 7.57 (m, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 156.81, 154.09, 142.14, 135.56, 129.94, 129.17, 129.12, 128.64, 126.52, 122.56 (q, J = 289.2 Hz), 121.80, 117.65, 116.24, 111.55, 77.98 - 76.73 (m). 19 F NMR (377 MHz, DMSO-d6) δ -72.26

[0072] Example 10

[0073]

[0074] Example 10 Figure 10 Under air atmosphere, 7-methoxy-3-trifluoromethylbenzopyrone 1j (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a 60 degree reaction module overnight. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was carried out until a small amount of liquid was left. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the eluent used was petroleum ether and ethyl acetate prepared in a ratio of 10:1. The product data characterization: (PE:EA = 10:1, Rf = 0.42, white solid, 66% yield). The nuclear magnetic resonance results of compound 3j are shown in f Figure 10 1 H NMR (400 MHz, Chloroform-d) δ 8.53 (s, 1H), 8.08 (s, 1H), 7.54 (d, J = 8.7 Hz, 1H), 6.99 (dd, J = 8.7, 2.4 Hz, 1H), 6.88 (d, J = 2.3 Hz, 1H), 3.93 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 165.08, 162.92, 155.33, 145.45, 130.68, 122.48 (q, J = 289.1 Hz), 114.69, 111.62, 110.25, 100.43, 77.96 - 76.48 (m), 56.18.19 F NMR (377 MHz, Chloroform-d) δ -76.26

[0075] Example 11

[0076]

[0077] To a 10 mL reaction vial, 8-methoxy-3-trifluoromethylbenzopyrone 1k (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added under air atmosphere, and the reaction was carried out in a 60-degree reaction module overnight. The resulting reaction solution was poured into a round-bottom flask, and rotary evaporation was carried out until a small amount of liquid remained. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the target product (3k) was obtained. The eluent used was petroleum ether and ethyl acetate prepared in a ratio of 10:1. Product data characterization: (PE:EA = 10:1, Rf = 0.48, white solid, 55% yield). The nuclear magnetic resonance results of compound 3k are shown in f Figure 11 1 H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 8.15 (s, 1H), 7.36 (t, J = 8.0 Hz, 1H), 7.23 (d, J = 8.3 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 3.99 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 162.11, 147.13, 145.95, 142.69, 125.94, 122.33 (q, J = 288.3 Hz), 120.49, 118.41, 115.87, 114.47, 77.95-77.25 (m), 56.36. 19 F NMR (377 MHz, Chloroform-d) δ -76.18.

[0078] Example 12

[0079]

[0080] ​​Under air atmosphere, 8-ethoxy-3-trifluoroacetylbenzopyrone 1l (1.0 mmol), trifluoromethylsilane 2a (1.0 mmol), cesium carbonate (50 mol%) and solvent DMF (2 mL) were added to a 10 mL reaction bottle and reacted overnight in a reaction module at 50 degrees. The resulting reaction solution was poured into a round-bottom flask and rotary evaporated until a small amount of liquid remained. An appropriate amount of silica gel was added and rotary evaporated until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography to obtain the target product (3l). The eluent used was petroleum ether and ethyl acetate in a ratio of 10:1. Product data characterization: (PE:EA=10:1, R f =0.52, white solid, 48% yield). The NMR results of compound 31 are as follows Figure 12 As shown, 1 H NMR (400MHz, CDCl3) δ8.50(d,J=3.1Hz,1H),8.06(d,J=2.9Hz,1H),7.25(t,J=6.2Hz,1 H),7.17-7.07(m,2H),4.13(d,J=2.9Hz,1H),4.11(d,J=7.2Hz,1H),1.47-1.38(m,3H). 13 C NMR(101MHz,Chloroform-d)δ162.31,146.54,146.03,142.86,125.93,122.36( q, J=288.5Hz),120.38,118.52,116.90,114.36,77.96,78.05-76.67(m),14.55. 19 F NMR(377MHz,Chloroform-d)δ-76.19.

[0081] Example 13

[0082]

[0083] Under air atmosphere, 3-trifluoroacetylbenzopyrone 1m (1.0mmol), trifluoromethylsilane 2a (3.0mmol), cesium fluoride (20mol%) and ultra-dry THF (1mL) were added to a 10mL reaction bottle and reacted overnight in a reaction module at 60 degrees. The resulting reaction solution was poured into a round-bottom flask and rotary evaporated until a small amount of liquid remained. An appropriate amount of silica gel was added and rotary evaporated until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography to obtain the target product (3m). The eluent used was petroleum ether and ethyl acetate in a ratio of 20:1. Product data characterization: (PE:EA=20:1, R f =0.52, light yellow solid, 57% yield). The NMR results of compound 3m are as followsFigure 13 as shown, 1 H NMR (400 MHz, Chloroform-d) δ 7.35 - 7.28 (m, 1H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (td, J = 7.5, 1.1 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 0.26 (s, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 148.72, 130.85, 130.81, 130.38, 127.11, 122.68, 122.19, 120.34 (q, J = 292.6 Hz), 119.56, 116.00, 113.13, 77.94, -0.45. 19 F NMR (377 MHz, Chloroform-d) δ -71.87, -74.31 (d, J = 8.9 Hz), -83.82.

[0084] Example 14

[0085]

[0086] Under air atmosphere, 5-chloro-3-trifluoroacetylbenzopyrone 1n (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent super dry THF (1 mL) were added into a 10 mL reaction vial, and the reaction was carried out in a reaction module at 120 degrees overnight. The resulting reaction solution was poured into a round bottom flask, and rotary evaporation was carried out until a small amount of liquid was left. An appropriate amount of silica gel was added, and rotary evaporation was continued until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography, and the eluent used was petroleum ether and ethyl acetate prepared in a ratio of 20: 1. The product data characterization: (PE: EA = 20: 1, Rf = 0.44, yellow-green solid, yield: 41%, m.p. 52-54 °C). The nuclear magnetic results of compound 3n are shown in f Figure 14 as shown, 1 H NMR (400 MHz, Chloroform-d) δ 7.35 - 7.28 (m, 1H), 7.19 (dd, J = 7.6, 1.6 Hz, 1H), 7.03 (td, J = 7.5, 1.1 Hz, 1H), 6.93 (d, J = 8.1 Hz, 1H), 0.26 (s, 9H). 13 ​C NMR(101MHz,Chloroform-d)δ149.69,131.52,130.34,127.12,122.07,121. 80,120.63(q,J=289.9Hz),118.75,114.68,111.98,76.80-75.14(m),-1.51. 9 F NMR (377MHz, Chloroform-d) δ -71.95 (d, J = 9.2Hz), -74.07 (d, J = 8.5Hz), -83.53.

[0087] Example 15

[0088]

[0089] Under air atmosphere, 6-methyl-3-trifluoroacetylbenzopyrone 1o (1.0 mmol), trifluoromethylsilane 2a (2.0 mmol), cesium acetate (100 mol%) and ultra-dry THF (4 mL) were added to a 10 mL reaction bottle and reacted in a reaction module at 120 degrees for 5 h. The resulting reaction solution was poured into a round-bottom flask and rotary evaporated until a small amount of liquid remained. An appropriate amount of silica gel was added and rotary evaporated until all the product was loaded onto the silica gel. The product was separated by silica gel column chromatography to obtain the target product (3o). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 20:1. Product data characterization: (PE:EA=20:1, R f =0.39, light yellow solid, 47% yield). The NMR results of compound 3o are as follows Figure 15 As shown, 1 H NMR (400MHz, Chloroform-d) δ8.56(s,1H),8.12(s,1H),7.52(d,J=8.5Hz,1H),7.46(s,1H),7.33(d,J=8.5Hz,1H),2.46(s,3H). 13 C NMR(101MHz,Chloroform-d)δ156.87,152.42,145.64,134.60,134.57,128.73, 122.25(q,J=290.7Hz),120.23,117.45,116.15,78.55-76.52(m),20.66,1.32. 19 F NMR(377MHz,Chloroform-d)δ-76.13.

[0090] Bactericidal activity test:

[0091] The activity of the 6 kinds of pathogenic bacteria commonly found in agricultural production was determined, which were peanut Sclerotium rolfsii, tomato Botrytis cinerea, wheat Helminthosporium turcicum, wheat Gaeumannomyces graminis, Fusarium oxysporum, and Fusarium moniliforme. 6.6 mg of the above-synthesized drug was dissolved in 3.3 mL of DMSO, and then 1% Tween 80 in water was added to prepare a 2 mg / mL technical material. The test agent was taken in a sterile condition, and then shaken well in a conical flask. Then, an equal amount was poured into three culture dishes with a diameter of 9 cm to prepare a 100-200 μg / mL drug-containing plate. The above experiment was set up without the drug agent as a blank control, and each treatment was repeated three times. The cultured pathogenic bacteria were cut into a bacterial cake along the edge of the colony under sterile conditions using a 5 mm puncher, and the bacterial cake was inoculated in the center of the drug-containing plate using an inoculator, with the mycelium facing up. The culture dish was placed in a 25°C constant temperature incubator for incubation. When the control colony diameter expanded to more than 6 cm, the colony diameter was measured by cross method, and the average value was taken. The inhibition rate was calculated at the end of the incubation.

[0092] The calculation formula is: inhibition rate I = (D0-D t ) / D0x100%

[0093] D0 is the average diameter of the control plate mycelium, and D t is the average diameter of the sample plate mycelium.

[0094] The results show that the 15 new coumarin tertiary alcohol compounds 3a-3o containing bistrifluoromethyl synthesized in Examples 1-15 have certain inhibition on 6 different pathogenic bacteria. Among them, the compounds 3a-3o show excellent bactericidal activity on wheat Gaeumannomyces graminis, and seven compounds can reach 100% inhibition at 200 ppm. The inhibition effect of other compounds is shown in Figures 16-21 .

[0095] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A tertiary coumarin alcohol compound containing a bis(trifluoromethyl) group, characterized in that: The structural formula of the coumarin tertiary alcohol compound is as follows: 、 、 、 、 、 、 、 、 、 or .

2. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 1, characterized in that: The method comprises the following steps: mixing a trifluoroacetylcoumarin compound, a trifluoromethylsilane compound, a catalyst and a solvent to prepare a reaction solution, allowing the mixture to react fully, and purifying the mixture to obtain a tertiary coumarin alcohol compound containing a bistrifluoromethyl group; the structural formula of the trifluoroacetylcoumarin compound is shown below: , wherein R is consistent with the substituent at the corresponding position in the structural formula of the coumarin tertiary alcohol compound in claim 1; the catalyst is cesium fluoride, cesium acetate or cesium carbonate.

3. The method for preparing a bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 2, wherein: The amount of the catalyst is 20-100 mol%.

4. The method for preparing a bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 3, wherein: The solvent is tetrahydrofuran, N,N - dimethylformamide or acetonitrile.

5. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 3, wherein: The solvent is an ultra-dry solvent, and the ultra-dry solvent is tetrahydrofuran.

6. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 4 or 5, characterized in that: The molar ratio of the trifluoroacetylcoumarin compound to the trifluoromethylsilane compound is 1:(1-3).

7. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 6, characterized in that: The concentration of the trifluoroacetylcoumarin compound in the reaction solution is (0.25-1) mmol / mL.

8. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 7, wherein: The reaction temperature is 50-120° C., and the reaction time is 5-12 h.

9. Use of the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 1 in the field of agricultural antibacterial and sterilization, characterized in that: Used for agricultural fungi; the agricultural fungi are peanut white rot fungi, tomato gray mold fungi, wheat sheath blight fungi, wheat take-all fungi, Fusarium oxysporum or Fusarium moniliforme.

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