Coumarin tertiary alcohol compound containing bis (trifluoromethyl) as well as preparation method and application of coumarin tertiary alcohol compound

Abstract

The invention provides a coumarin tertiary alcohol compound containing bis (trifluoromethyl) as well as a preparation method and application thereof, belongs to the technical field of organic synthetic chemistry, and is used for solving the technical problems of single structure and poor bactericidal activity of the existing trifluoro tertiary alcohol compound. The structural formula of the coumarin tertiary alcohol compound is as follows: # imgabs0 #, wherein R is Me, OMe, OEt, F, Cl, Br or Ph. The preparation method comprises the following steps: mixing a trifluoroacetyl coumarin compound, a trifluoromethylsilane compound, a catalyst and a solvent to prepare a reaction solution, fully reacting, and purifying to obtain the coumarin tertiary alcohol compound. Synthesis of products in the field of bis (trifluoromethyl) tertiary alcohol and tertiary alcohol silyl ether compounds is broadened, and the compounds have excellent antibacterial activity, have good effects on many plant fungal diseases, are worthy of further exploration and have wide exploration and application space in the field of pesticides.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthetic chemistry, and in particular relates to a fluorine-containing coumarin tertiary alcohol and a derivative thereof. Background Art

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

[0003] Compound A is a fluorine-containing intermediate with great application value, which is widely used in the fields of pesticides, medicines, veterinary drugs, etc. It can be used as a raw material to produce the herbicide high-efficiency flupyralid, insecticides chlorpyrifos, pyrimidine, etc. Compound B is an insecticide disclosed in 2017, which has a good control effect on Spodoptera exigua, Trichoplusia ni and Aedes aegypti. Compound C is flupyridone, which is a neonicotinoid insecticide that acts on the acetylcholine receptors of insects. It is mainly used to control piercing-sucking mouthparts pests of vegetables, fruit trees and field crops. Compound D is an insecticide, which has a good insecticidal effect on peach aphids, brown planthoppers, etc. Compound E is an SDHI fungicide, which has a good effect on powdery mildew, gray mold, etc. Compound F is a triazole fungicide, which can be applied to a variety of crops such as corn, soybeans, and grains, and has both control and protection effects on crops.

[0004] Coumarin is a natural product widely distributed in plants such as Rutaceae, Umbelliferae, Leguminosae, Asteraceae and Orchidaceae. Coumarin derivatives have attracted wide attention due to their diverse structural types, multiple activities and low toxicity. They are widely used in the fields of medicine, bioactive antifungal drugs and other fields. The introduction of trifluoromethyl groups into the coumarin ketone structure is a common organic chemical synthesis strategy, which is often used to prepare compounds with specific biological activities. To obtain coumarin tertiary alcohol compounds and introduce trifluoromethyl groups into them, it is necessary to pay attention to selectively introduce a trifluoromethyl group into a specific position of the coumarin tertiary alcohol. However, when introducing fluorine groups into coumarin compounds, the existing synthesis methods may have the following disadvantages: such as reaction complexity, the introduction of fluorine groups may require a complex multi-step reaction sequence, including oxidation, reduction, halogenation and fluorination, and in the process of introducing fluorine groups, the final yield may be low due to side reactions or other chemical factors. Although there are some methods for introducing fluorine groups into synthetic coumarin compounds, there may still be problems such as unsatisfactory synthesis routes, harsh reaction conditions or long time. In addition, although multiple experimental data have shown that trifluorotertiary alcohol compounds have good biological activity, the bactericidal activity still needs to be further improved. Summary of the invention

[0005] In view of the above-mentioned technical problems, the present invention proposes a tertiary alcohol coumarin compound containing a bistrifluoromethyl group and a preparation method and application thereof, which broadens the synthesis of products in the field of bistrifluoromethyl tertiary alcohol and tertiary alcohol silyl ether compounds. Such compounds have excellent antibacterial activity and have good effects on a variety of plant fungal diseases. They are worthy of further exploration and have broad exploration and application space in the field of pesticides.

[0006] In order to achieve the above object, the technical solution of the present invention is achieved as follows:

[0007] A tertiary coumarin alcohol compound containing a bistrifluoromethyl group, wherein the structural formula of the tertiary coumarin alcohol compound is as follows:

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

[0009] A tertiary coumarin alcohol compound containing a bistrifluoromethyl group comprises the following steps: a trifluoroacetylcoumarin compound, a trifluoromethylsilane compound, a catalyst and a solvent are mixed to prepare a reaction liquid, the mixture is fully reacted, and the tertiary coumarin alcohol compound is prepared after purification.

[0010] The structural formula of the trifluoroacetylcoumarin compound is shown below:

[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), etc., and the amount of the catalyst is 20-100 mol%.

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

[0014] The solvent is an ultra-dry solvent (with a water content of less than 50 ppm), and the ultra-dry solvent is ultra-dry tetrahydrofuran.

[0015] The molar ratio of the trifluoroacetylcoumarin compound to the trifluoromethylsilane compound is 1:(1-3)mmol / mL.

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

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

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

[0019] Application of a bistrifluoromethyl-containing coumarin tertiary alcohol compound in the field of agricultural antibacterial and sterilization.

[0020] Beneficial effects of the present invention: The present invention innovatively selects commercially available coumarin ketone compounds and trifluoromethylsilane compounds as reactants, and realizes the synthesis of bistrifluoromethylcoumarin tertiary alcohol under the action of a catalyst, and verifies that it does have good, broad-spectrum bactericidal activity. At the same time, when the tetrahydrofuran solvent is in the state of an ultra-dry solvent, another bistrifluoromethylcoumarin tertiary alcohol silyl ether compound can be obtained.

[0021] The present invention realizes the construction of novel tertiary alcohol and tertiary alcohol silyl ether skeletons of coumarin containing bistrifluoromethyl, provides a simple and effective synthesis method for the construction of such skeletons, and the method has the characteristics of mild reaction conditions, simple operation, economical steps, strong functional group tolerance and good yield. The invention carries out fungicidal activity determination on 15 novel tertiary alcohol coumarin compounds containing bistrifluoromethyl synthesized, and the 15 compounds show certain fungicidal activity against six common pathogenic fungi in agricultural fungal diseases (peanut Sclerotium rolfsii, tomato gray mold, wheat sheath blight, wheat take-all pathogen, oxysporum Fusarium, and moniliforme Fusarium), among which excellent fungicidal activity is shown against the soil-borne disease wheat take-all pathogen, and the fungicidal rate of various compounds reaches 100% at 200ppm. In addition, the product obtained by the reaction has broad prospects for medical application, and at the same time provides a new idea and new method for the fields of industry, natural product synthesis and bioactive antifungal drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 is the NMR spectrum of compound 3a, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

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

[0025] Figure 3 is the NMR spectrum of compound 3c, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

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

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

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

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

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

[0031] Fig. 9 is the NMR spectrum of compound 3i, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

[0032] Fig.10 is the NMR spectrum of compound 3j, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

[0033] Fig.11 is the NMR spectrum of compound 3k, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

[0034] Fig.12 is the NMR spectrum of compound 3l, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

[0035] Fig.13 is the NMR spectrum of compound 3m, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

[0036] Fig.14 is the NMR spectrum of compound 3n, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

[0037] Fig.15 is the NMR spectrum of compound 3o, (a) is the NMR 1 H spectrum; (b) NMR 13 C spectrum; (c) NMR 19 F spectrum.

[0038] Fig.16The inhibition rates of 15 compounds against Sclerotium rolfsii at 100 ppm are shown.

[0039] Fig.17 The inhibition rate of 15 compounds against tomato gray mold at 100 ppm.

[0040] Fig.18 The inhibition rates of 15 compounds against wheat sheath blight at 100 ppm are shown.

[0041] Fig.19 The inhibition rates of 15 compounds against wheat take-all pathogen at 200 ppm are shown in Table 2.

[0042] Fig. 20 The inhibition rates of 15 compounds against Fusarium oxysporum at 100 ppm.

[0043] Fig.21 The inhibition rates of 15 compounds against Fusarium moniliforme at 100 ppm are shown in Table 2. DETAILED DESCRIPTION

[0044] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0045] Example 1

[0046]

[0047] Under air atmosphere, unsubstituted fluorinated benzopyrone 1a (1.0 mmol), trifluoromethylsilane 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 reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3a). The eluent used was prepared by petroleum ether and ethyl acetate in a ratio of 20:1. Product data characterization: (PE:EA=20:1, R f =0.36, light yellow solid, 72% yield). The NMR results of compound 3a are as follows Figure 1 As shown, 1H NMR (400MHz, Chloroform-d) δ8.49 (s, 1H), 8.18 (s, 1H), 7.77-7.70 (m, 1H), 7.67 (d, J = 7.8Hz, 1H), 7.45 (t, J = 8.2Hz, 2H). 13 C NMR (101MHz, Chloroform-d) δ145.80, 145.78, 145.75, 145.73, 145.70, 134.55, 129.63, 126.01, 122.21 (q, J = 288.6Hz), 116.83, 79.94-75.30 (m). 19 F NMR(377MHz,Chloroform-d)δ-76.12.

[0048] Example 2

[0049]

[0050] Under air atmosphere, 5-fluoro-3-trifluoroformylbenzopyrone 1b (1.0 mmol), trifluoromethylsilane 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 90 degree reaction module. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3b). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 20:1. Product data characterization: (PE:EA=10:1, R f =0.45, white solid, 52% yield). The NMR results of compound 3b are as follows Figure 2 As shown, 1 H NMR (400MHz, Chloroform-d) δ8.32 (s, 1H), 8.16 (s, 1H), 7.68-7.56 (m, 1H), 7.19 (d, J = 8.5Hz, 1H), 7.09 (t, J = 8.6Hz, 1H). 13 CNMR (101MHz, CDCl3) δ161.63, 158.98 (d, J = 259.5Hz), 153.35 (d, J = 4.1Hz), 138.64, 135.11 (d, J = 9.8Hz), 122.22 ( q,J=289.1,287.9Hz),114.91,112.72(d,J=4.1Hz),111.78(d,J=19.5Hz),108.38(d,J=18.7Hz),77.94-75.80(m). 19F NMR(377MHz, CDCl3)δ-75.99,-116.64.

[0051] Example 3

[0052]

[0053] Under air atmosphere, 5-chloro-3-trifluoroformylbenzopyrone 1c (1.0mmol), trifluoromethylsilane 2a (3.0mmol), cesium fluoride (20mol%) and solvent THF (1mL) were added to a 10mL reaction bottle, and reacted in a reaction module at 60 degrees for 5 hours. 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3c). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 10:1. Product data characterization: (PE:EA=10:1, Rf=0.47, green solid, 61% yield). The NMR results of compound 3c are shown as follows Figure 3 As shown, 1 H NMR (400MHz, Chloroform-d) δ8.57(s,1H),8.24(s,1H),7.64(t,J=8.2Hz,1H),7.48(dd,J=8.0,1.1Hz,1H),7.36(d,J=8.5Hz,1H). 13 C NMR (101MHz, CDCl3) δ161.60,153.82,142.07,142.04,142.02,141.99,141.96,134.4 6,133.99,126.53,122.21(q,J=288.6Hz),116.49,115.66,115.46,78.35-76.68(m). 19 FNMR (377MHz,CDCl3)δ-76.03.

[0054] Example 4

[0055]

[0056] Under air atmosphere, 5,7-dimethoxy-3-trifluoroformylbenzopyrone 1d (1.0 mmol), trifluoromethylsilane 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 reaction module at 100 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3d). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 50:1. Product data characterization: (PE:EA=50:1, R f =0.38, white solid, 44% yield). The NMR results of compound 3d are as follows Figure 4 As shown, 1 H NMR (400MHz, CDCl3) δ8.55(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 (101MHz, CDCl3) δ166.18,163.22,157.98,156.14,140.85,122.53(q,J =288.1Hz),107.94,103.69,96.02,92.44,77.85-76.21(m),56.33,56.21. 19 F NMR(377MHz,Chloroform-d)δ-76.35.

[0057] Example 5

[0058]

[0059] Under air atmosphere, 6-fluoro-3-trifluoroformylbenzopyrone 1e (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added to a 10 mL reaction bottle, and the reaction was carried out overnight in a reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3e). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 30:1. Product data characterization: (PE:EA=30:1, R f =0.42, white solid, 75% yield). The NMR results of compound 3e are as follows Figure 5 As shown, 1H NMR (400MHz, CDCl3) δ8.35 (s, 1H), 8.12 (s, 1H), 7.45 (d, J = 1.7Hz, 1H), 7.44 (d, J = 1.7Hz, 1H), 7.36 (d, J = 7.3Hz, 1H). 13 CNMR(101MHz, CDCl3)δ161.92,159.38(d,J=247.7Hz),149.30,144.67(q,J=3.0Hz),123.67,122.19(q, J=24.7Hz),118.68(d,J=8.6Hz),118.44(d,J=9.3Hz),115.89,114.72(d,J=24.5Hz),78.96-75.00(m). 19 F NMR(377MHz,Chloroform-d)δ-75.98,-114.37.

[0060] Example 6

[0061]

[0062] Under air atmosphere, 6-chloro-3-trifluoroformylbenzopyrone 1f (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added to a 10 mL reaction bottle, and the reaction was carried out overnight in a reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3f). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 10:1. Product data characterization: (PE:EA=10:1, R f =0.42, green solid, 72% yield). The NMR results of compound 3f are as follows Figure 6 As shown, 1 H NMR (400MHz, Chloroform-d) δ8.28 (s, 1H), 8.11 (s, 1H), 7.67 (d, J = 10.5Hz, 2H), 7.40 (d, J = 7.4Hz, 1H). 13 C NMR (101MHz, CDCl3) δ161.78,151.45,144.53,134.45,131.49,128.74,122.23(q,J=288.0Hz),118.71,118.33,117.93,115.85,78.46-76.80(m). 19F NMR(377MHz,Chloroform-d)δ-76.01.

[0063] Example 7

[0064]

[0065] Under air atmosphere, 6-chloro-3-trifluoroformylbenzopyrone 1g (1.0mmol), trifluoromethylsilane 2a (3.0mmol), cesium fluoride (20mol%) and solvent THF (1mL) were added to a 10mL reaction bottle, and reacted overnight in a reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3g). The eluent used was prepared by petroleum ether and ethyl acetate in a ratio of 20:1. Product data characterization: (PE:EA=20:1, R f =0.53, brown solid, 41% yield). The NMR results of compound 3g are as follows Figure 7 As shown, 1 H NMR (400MHz, CDCl3) δ8.26(s,1H),8.10(s,1H),7.83(s,1H),7.80(d,J=8.8Hz,1H),7.34(d,J=8.8Hz,1H). 13 CNMR(101MHz, CDCl3)δ161.71,151.90,144.46,137.24,131.81,122.22(q,J=288.7Hz),119.16,118.69,118.53,115.79,78.50-76.36(m). 19 F NMR (377 MHz, CDCl3) δ-76.01.

[0066] Example 8

[0067]

[0068] Under air atmosphere, 6-methyl-3-trifluoroformylbenzopyrone 1h (1.0mmol), trifluoromethylsilane 2a (3.0mmol), cesium fluoride (20mol%) and solvent THF (1mL) were added to a 10mL reaction bottle, and reacted overnight in a reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3h). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 10:1. Product data characterization: (PE:EA=10:1, R f =0.65, yellow solid, 77% yield). The NMR results of compound 3h are as follows Figure 8 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, CDCl3) δ162.66,151.31,145.67,136.04,135.62,129.26,122 .40(d,J=288.7Hz),117.62,116.55,114.21,122.40(d,J=288.7Hz),20.77. 19 F NMR(377MHz,Chloroform-d)δ-76.13.

[0069] Example 9

[0070]

[0071] Under air atmosphere, 5,6-phenyl-3-trifluoroformylbenzopyrone 1I (1.0mmol), trifluoromethylsilane 2a (3.0mmol), cesium fluoride (20mol%) and solvent THF (1mL) were added to a 10mL reaction bottle, and reacted overnight in a reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3i). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 10:1. Product data characterization: (PE:EA=10:1, R f =0.54, light yellow solid, 63% yield). The NMR results of compound 3i are as follows Fig. 9 As shown, 1H NMR (400MHz, DMSO-d6) δ9.27 (s, 1H), 9.19 (s, 1H), 8.50 (d, J = 8.5Hz, 1H), 8.32 (d ,J=9.1Hz,1H),8.10(d,J=8.1Hz,1H),7.81(t,J=7.7Hz,1H),7.70-7.57(m,2H). 13 C NMR (101MHz, DMSO-d6) δ156.81,154.09,142.14,135.56,129.94,129.17,129.12,128. 64,126.52,122.56(q,J=289.2Hz),121.80,117.65,116.24,111.55,77.98-76.73(m). 19 F NMR (377MHz, DMSO-d6) δ-72.26

[0072] Example 10

[0073]

[0074] Under air atmosphere, 7-methoxy-3-trifluoroformylbenzopyrone 1j (1.0 mmol), trifluoromethylsilane 2a (3.0 mmol), cesium fluoride (20 mol%) and solvent THF (1 mL) were added to a 10 mL reaction bottle, and the reaction was carried out overnight in a reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3j). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 10:1. Product data characterization: (PE:EA=10:1, R f =0.42, white solid, 66% yield). The NMR results of compound 3j are as follows Fig.10 As shown, 1 H NMR (400MHz, Chloroform-d) δ8.53(s,1H),8.08(s,1H),7.54(d,J=8.7Hz,1H),6.99(dd,J=8.7,2.4Hz,1H),6.88(d,J=2.3Hz,1H),3.93(s,3H). 13 C NMR(101MHz,Chloroform-d)δ165.08,162.92,155.33,145.45,130.68,122. 48(q,J=289.1Hz),114.69,111.62,110.25,100.43,77.96-76.48(m),56.18.19 F NMR(377MHz,Chloroform-d)δ-76.26

[0075] Embodiment 11

[0076]

[0077] Under air atmosphere, 8-methoxy-3-trifluoroformylbenzopyrone 1k (1.0mmol), trifluoromethylsilane 2a (3.0mmol), cesium fluoride (20mol%) and solvent THF (1mL) were added to a 10mL reaction bottle, and reacted overnight in a reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3k). The eluent used was a mixture of petroleum ether and ethyl acetate in a ratio of 10:1. Product data characterization: (PE:EA=10:1, R f =0.48, white solid, 55% yield). The NMR results of compound 3k are as follows Fig.11 As shown, 1 H NMR (400MHz, CDCl3) δ8.53(s,1H),8.15(s,1H),7.36(t,J=8.0Hz,1H),7.23(d,J=8.3Hz,1H),7.20(d,J=7.8Hz,1H),3.99(s,3H). 13 C NMR(101MHz,Chloroform-d)δ162.11,147.13,145.95,142.69,125.94,122. 33(q,J=288.3Hz),120.49,118.41,115.87,114.47,77.95-77.25(m),56.36. 19 F NMR(377MHz,Chloroform-d)δ-76.18.

[0078] Example 12

[0079]

[0080] Under air atmosphere, 8-ethoxy-3-trifluoroacetylbenzopyrone 1l (1.0mmol), trifluoromethylsilane 2a (1.0mmol), cesium carbonate (50mol%) and solvent DMF (2mL) were added to a 10mL reaction bottle, and reacted overnight in a reaction module at 50 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3l). The eluent used was prepared by 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 Fig.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] Embodiment 13

[0082]

[0083] Under air atmosphere, 3-trifluoroacetylbenzopyrone 1m (1.0mmol), trifluoromethylsilane 2a (3.0mmol), cesium fluoride (20mol%) and solvent ultra-dry THF (1mL) were added to a 10mL reaction bottle, and reacted overnight in a reaction module at 60 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3m). 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 =0.52, light yellow solid, 57% yield). The NMR results of compound 3m are as follows Fig.13 As shown, 1 H NMR (400MHz, Chloroform-d) δ7.35-7.28(m,1H),7.19(dd,J=7.6,1.6Hz,1H),7.03(td,J=7.5,1.1Hz,1H),6.93(d,J=8.1Hz,1H),0.26(s,9H). 13 C NMR (101MHz, Chloroform-d) δ 148.72, 130.85, 130.81, 130.38, 127.11, 122.68, 122.19, 120.34 (q, J = 292.6Hz), 119.56, 116.00, 113.13, 77.94, -0.45. 19 FNMR(377MHz,Chloroform-d)δ-71.87,-74.31(d,J=8.9Hz),-83.82.

[0084] Embodiment 14

[0085]

[0086] Under air atmosphere, 5-chloro-3-trifluoroacetylbenzopyrone 1n (1.0mmol), trifluoromethylsilane 2a (3.0mmol), cesium fluoride (20mol%) and solvent ultra-dry THF (1mL) were added to a 10mL reaction bottle, and the reaction was carried out overnight in a reaction module at 120 degrees. The obtained 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 products were loaded on the silica gel. The products were separated by silica gel column chromatography to obtain the target product (3n). 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 =0.44, yellow-green solid, yield: 41%, mp 52-54°C). The NMR results of compound 3n are as follows Fig.14 As shown, 1 H NMR (400MHz, Chloroform-d) δ7.57(s,1H),7.21(t,J=8.1Hz,1H),7.04(d,J=8.0Hz,1H),6.82(d,J=8.2Hz,1H),0.22(s,9H). 13C 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] Embodiment 15

[0088]

[0089] Under air atmosphere, 6-methyl-3-trifluoroacetylbenzopyrone 1o (1.0 mmol), trifluoromethylsilane 2a (2.0 mmol), cesium acetate (100 mol%) and solvent 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 products were loaded on the silica gel. The products were 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 Fig.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 6 common pathogens in agricultural production was measured, namely peanut white rot fungus, tomato gray mold fungus, wheat eye spot fungus, wheat take-all fungus, oxysporum fungus, and moniliforme fungus. Take 6.6 mg of the above-synthesized drug and dissolve it in 3.3 mL DMSO, then add an aqueous solution containing 1% Tween 80 to make a 2 mg / mL original drug. Pipette an appropriate amount of the test agent into a conical flask under sterile conditions, shake it well, and then pour an equal amount into three culture dishes with a diameter of 9 cm to make a 100-200 μg / mL drug-containing plate. The above experiment sets the treatment without the drug as a blank control, and each treatment is repeated three times. Use a 5 mm diameter puncher to cut the cultured pathogens along the edge of the colony under sterile conditions, and use an inoculator to inoculate the cake in the center of the drug-containing plate with the mycelium side facing up. Cover the plate with a lid and place the culture plate in a constant temperature incubator at 25 degrees Celsius for culture. When the diameter of the control colony expands to more than 6 cm, measure the colony diameter using the cross method and take the average value. Calculate the inhibition rate at the end of the culture.

[0092] The calculation formula is: Inhibition rate I = (D0-D t ) / D0×100%

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

[0094] The results show that the 15 novel bis-trifluoromethyl-containing coumarin tertiary alcohol compounds 3a-3o synthesized in Examples 1-15 all have certain inhibitory effects on 6 different pathogens, among which compounds 3a-3o show excellent fungicidal activity against wheat take-all pathogen, and the inhibition rate of seven compounds can reach 100% under the condition of 200ppm. The inhibitory effects of other compounds are detailed in Figure 16-21 .

[0095] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A tertiary alcohol coumarin compound containing a bistrifluoromethyl group, characterized in that: The structural formula of the coumarin tertiary alcohol compound is as follows: In the formula, R is Me, OEt, OMe, F, Cl, Br or Ph.

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 liquid, allowing the mixture to fully react, and obtaining a bistrifluoromethyl-containing coumarin tertiary alcohol compound after purification.

3. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 2, characterized in that: The structural formula of the trifluoroacetylcoumarin compound is shown below: In the formula, R is Me, OEt, OMe, F, Cl, Br or Ph.

4. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 2, characterized in that: The catalyst is cesium fluoride, cesium acetate or cesium carbonate, and the amount of the catalyst is 20-100 mol%.

5. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 4, characterized in that: The solvent is tetrahydrofuran, N,N-dimethylformamide or acetonitrile.

6. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 4, characterized in that: The solvent is an ultra-dry solvent, and the ultra-dry solvent is tetrahydrofuran.

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

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

9. The method for preparing the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 8, characterized in that: The reaction temperature is 50-120° C., and the reaction time is 5-12 hours.

10. Use of the bistrifluoromethyl-containing coumarin tertiary alcohol compound according to claim 1 in the field of agricultural antibacterial and sterilization.

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