Indole isothiocyanate compound, preparation method and application

Abstract

This invention belongs to the field of pathogen control technology and specifically relates to an indole isothiocyanate compound, its preparation method, and its application. This invention introduces an isothiocyanate group into various indole compounds to produce a class of compounds with novel structures. The structure of these compounds is shown in Formula I. These compounds exhibit broad-spectrum fungicidal activity, particularly against apple blight, tomato gray mold, pepper phytophthora, and tobacco alternatant. They can be used as fungicides to control these plant diseases. #imgabs0#

Description

Technical Field

[0001] The present invention belongs to the technical field of pathogen control, and in particular relates to an indole isothiocyanate compound, a preparation method and an application thereof. Background Art

[0002] Humans are increasingly demanding higher and higher levels of food quality and quantity. Crop diseases caused by fungi and oomycetes annually cause significant economic losses and safety issues for the food and agricultural sectors, and their impacts are receiving widespread attention. Tomato gray mold is a widespread and devastating disease, and resistance to commercially available agents such as diethofencarb and procymidone is becoming increasingly prominent. Therefore, there is an urgent need to develop a new, low-toxic, highly effective, and multifunctional fungicide to avoid the safety and resistance issues associated with the long-term, large-scale use of certain single antimicrobial agents (Qu et al., ACS Appl. Mater. Interfaces., 2017, 9, 37; Natividad et al., J. Agric. Food Chem., 2015, 63, 14). Summary of the Invention

[0003] To discover new agricultural fungicides, the present invention introduces isothiocyanate groups into various indole compounds to obtain a class of novel compounds with excellent antibacterial activity. To this end, the present invention provides an indole isothiocyanate compound, a preparation method, and its application.

[0004] The structural formula of the indole isothiocyanate compound provided by the present invention is shown in Formula I;

[0005]

[0006] wherein the R group is selected from 2-CH3, 3-CH3, 5-CH3, 7-CH3, 2,3-CH3, 2,5-CH3, 4-OCH3, 6-OCH3, 7-OCH3, 4-benzyloxy, 4-Cl, 5-Cl, 6-Cl, 7-Cl, 6-F, 4-NO2, 5-NO2, 6-NO2, 7-NO2, 4-Br, 6-Br or 7-Br.

[0007] The preparation method of the above-mentioned indole isothiocyanate compound comprises the following steps:

[0008] Step 1: reacting the compound represented by Formula II with 1,3-dibromopropane in a first organic solvent at room temperature in the presence of a basic salt to obtain a compound represented by Formula IV;

[0009]

[0010] Step 2: reacting the compound represented by Formula IV with sodium thiocyanate in a second organic solvent at 45-55° C., then heating to 60-85° C. and continuing the reaction to obtain the compound represented by Formula I.

[0011] An optional scheme is that the first organic solvent is selected from acetonitrile or N,N-dimethylformamide; the alkaline salt is selected from potassium hydroxide or sodium hydroxide; the molar ratio of the compound represented by formula II, the alkaline salt and 1,3-dibromopropane is 1:1:(1 to 2.5); the reaction time of step 1 is 6 to 8 hours; the second organic solvent is selected from ethanol; the molar ratio of the compound represented by formula IV and sodium thiocyanate is 1:(1 to 2.5); the reaction time of step 2 is 5 to 8 hours; the reaction time is 4 to 8 hours under conditions of 60 to 85°C.

[0012] The indole isothiocyanate compounds of the present invention are used for preparing plant fungicides.

[0013] The indole isothiocyanate compounds prepared by the preparation method of the present invention are used in preparing plant fungicides.

[0014] The indole isothiocyanate compound of the present invention is used for preparing a fungicide for preventing and treating apple tree rot, tomato gray mold, pepper phytophthora and tobacco brown spot disease.

[0015] The indole isothiocyanate compounds prepared by the preparation method of the present invention are used for preparing fungicides for preventing and treating apple tree rot, tomato gray mold, pepper phytophthora and tobacco brown spot disease.

[0016] The present invention introduces isothiocyanate groups into different indole compounds. The obtained compounds have novel structures and good fungicidal activity, especially having obvious inhibitory effects on apple tree rot bacteria, tomato gray mold bacteria, pepper phytophthora bacteria and tobacco brown spot disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The accompanying drawings are used to provide a further understanding of the present disclosure and constitute a part of the specification. Together with the following detailed description, they are used to explain the present disclosure but do not constitute a limitation of the present disclosure. In the accompanying drawings:

[0018] Figure 1 The carbon spectrum (A) and hydrogen spectrum (B) of compound I-02 of the present invention are shown.

[0019] Figure 2 The carbon spectrum (A) and hydrogen spectrum (B) of compound I-06 of the present invention are shown.

[0020] Figure 3 The carbon spectrum (A) and hydrogen spectrum (B) of compound I-09 of the present invention are shown.

[0021] Figure 4 The carbon spectrum (A) and hydrogen spectrum (B) of compound I-13 of the present invention are shown.

[0022] Figure 5 The carbon spectrum (A) and hydrogen spectrum (B) of compound I-14 of the present invention are shown.

[0023] Figure 6 The carbon spectrum (A) and hydrogen spectrum (B) of compound I-16 of the present invention are shown.

[0024] Figure 7 The carbon spectrum (A) and hydrogen spectrum (B) of compound I-21 of the present invention are shown. DETAILED DESCRIPTION

[0025] Unless otherwise specified, the scientific and technical terms used herein are understood according to the knowledge of ordinary technicians in the relevant fields.

[0026] The present invention is further described below with reference to specific examples, but the present invention is not limited to these examples. The methods described are conventional methods unless otherwise specified. The materials described are commercially available unless otherwise specified.

[0027] The preparation route of the compound of the present invention is as follows: specifically, the compound represented by formula II is reacted with the compound represented by formula III (1,3-dibromopropane) in an organic solvent to obtain the compound represented by formula IV, the compound represented by formula IV is reacted with the compound represented by formula V (sodium thiocyanate) in an organic solvent to obtain the compound represented by formula VI, and then the temperature is increased to continue the reaction to obtain the compound represented by formula I.

[0028]

[0029] The indole isothiocyanate compounds disclosed in the present invention have the general structural formula of Formula I;

[0030]

[0031] For more details, see the data listed in Table 1:

[0032] Table 1

[0033]

[0034]

[0035]

[0036]

[0037]

[0038] It should be noted that, based on the disclosure of the present invention, the technology in the art can optimize the ratio of the reaction materials, temperature, time, etc. to obtain the corresponding compound. The following are examples of the preparation of the compounds of the present invention, but the preparation method of the compounds of the present invention is not limited thereto. Unless otherwise specified, the reagent ratios used in the following examples are all molar ratios.

[0039] Example 1: Preparation of compound 2-methylindole-1-propyl isothiocyanate (I-01)

[0040]

[0041] Step 1: Add 2-methylindole (0.005 mol) and KOH powder (0.005 mol) to a reaction vessel, stir, use acetonitrile as solvent, add 1,3-dibromopropane (0.005 mol) dropwise at room temperature, react for 6 hours, and spin-dry the reaction solution to obtain an intermediate for use;

[0042] Step 2: In another reaction vessel, add NaSCN (0.01 mol) and ethanol: water = 1:1 (30 mL in total) as solvent. When the water bath is heated to 50°C, add the intermediate obtained in step 1 dropwise using a constant pressure low liquid funnel. After the addition is complete, react at 50°C for 5 hours; then heat to 80°C and continue the reaction for 5 hours.

[0043] After the reaction is completed, the mixture is filtered while hot, rotary evaporated at 40°C, washed with anhydrous ethanol, and separated by column chromatography to obtain a yellow oily liquid. 1 H NMR (500MHz, CDCl3) δ7.58 (ddd, J = 6.9, 2.1, 1.4Hz, 1H), 7.50-7.32 (m, 1H), 7.31-7.16 (m, 2H), 6. 78(d,J=2.7Hz,1H),3.94(t,J=5.4Hz,2H),3.48(t,J=6.2Hz,2H),2.26(s,3H),2.19-2.04(m,2H); 13 C NMR (125MHz, CDCl3) δ136.66,136.04,128.22,120.96,120.03,119.72,111.73,108.68,100.98,40.79,31.00,30.33,12.90.

[0044] According to the same method as the preparation of compound I-01, various indole compounds were used to replace the corresponding products I-02 to I-22. 1 H NMR, 13 The C NMR spectrum data are shown below.

[0045] 3-Methylindole-1-propyl isothiocyanate (I-02), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.55 (d, J = 7.8Hz, 1H), 7.23-7.04 (m, 3H), 6.77 (s, 1H), 4.13 (t, J = 6.4Hz, 2H), 2.65 (t, J = 7.0Hz, 2H), 2.32-2.17 (m, 5H); 13 C NMR (125MHz, CDCl3) δ136.29,129.05,125.26,121.99,119.43,119.13,111.92,111.29,109.09,43.37,30.90,30.33,9.78.

[0046] 5-Methylindole-1-propyl isothiocyanate (I-03), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.51-7.30(m,1H),7.19(d,J=8.4Hz,1H),7.11-6.93(m,2H),6.41(dd,J=3.2, 0.8Hz,1H),4.23(t,J=6.3Hz,2H),2.70(t,J=6.9Hz,2H),2.46(d,J=5.3Hz,3H),2.35-2.22(m,2H); 13 C NMR (125MHz, CDCl3) δ134.26,130.60,129.06,127.66,123.63,120.96,111.75,108.89,101.57,43.65,30.82,30.12,21.46.

[0047] 7-Methylindole-1-propyl isothiocyanate (I-04), yellow oily liquid 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 7.8 Hz, 1H), 7.11-6.94 (m, 3H), 6.62-6.43 (m, 1H), 4.51 (t, J = 6.5 Hz, 2H), 2.92-2.68 (m, 5H), 2.31 (p, J = 6.7 Hz, 2H); 13 C NMR (101MHz, CDCl3) δ134.41,130.04,129.19,125.13,120.50,120.07,119.44,111.59,102.52,46.18,32.32,30.79,19.99.

[0048] 2,3-Dimethylindole-1-propyl isothiocyanate (I-05), red oily liquid, 1 H NMR (500MHz, CDCl3) δ7.51 (dd, J=7.1, 1.4Hz, 1H), 7.35 (ddd, J=7.5, 6.4, 1.3Hz, 1H), 7.25-6.95 (m, 2H ),3.92(t,J=5.4Hz,2H),3.48(t,J=6.2Hz,2H),2.34(s,3H),2.15(tt,J=6.1,5.4Hz,2H).2.06(s,3H); 13 C NMR (125MHz, CDCl3) δ138.06,134.26,130.99,127.86,125.58,119.71,117.75,111.90,110.34,44.30,39.81,28.32,10.20,9.03.

[0049] 2,5-Dimethylindole-1-propane isothiocyanate (I-06), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.30 (s, 1H), 7.12 (d, J = 8.3Hz, 1H), 6.97 (d, J = 8.3Hz, 1H), 6.17 (s, 1H), 4. 18(t,J=6.7Hz,2H),2.81(t,J=7.1Hz,2H),2.41(d,J=6.8Hz,6H),2.25(dt,J=15.1,7.5Hz,2H); 13 CNMR(125MHz, CDCl3)δ136.04,135.05,128.91,128.47,122.42,119.82,111.72,108.36,100.49,40.80,31.01,30.36,21.43,12.92.

[0050] 4-Methoxyindole-1-propyl isothiocyanate (I-07), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.46(dd,J=6.6,1.3Hz,1H),7.32(dd,J=7.5,6.6Hz,1H),7.26(d,J=5.1Hz,1H),7.11(dd,J=7.8,1 .4Hz,1H),6.67(d,J=5.3Hz,1H),4.01(t,J=5.3Hz,2H),3.92(s,3H),3.44(t,J=6.2Hz,2H),2.15(tt,J=6.2,5.3Hz,2H); 13C NMR (125MHz, CDCl3) δ152.36,137.93,130.99,128.51,121.56,121.20,108.85,103.71,97.63,55.21,44.50,44.30,28.85.

[0051] 6-Methoxyindole-1-propyl isothiocyanate (I-08), red oily liquid, 1 H NMR (500MHz, CDCl3) δ7.62(dd,J=7.9,1.1Hz,1H),7.33(d,J=5.1Hz,1H),7.27(d,J=2.2Hz,1H),6.96(dd,J=7.9,2. 2Hz,1H),6.45-6.32(m,1H),4.01(t,J=5.3Hz,2H),3.83(s,3H),3.46(t,J=6.2Hz,2H),2.15(tt,J=6.2,5.3Hz,2H); 13 C NMR (125MHz, CDCl3) δ156.47,136.57,126.51,122.91,121.83,111.30,109.62,102.04,92.84,55.82,43.54,31.33,29.60.

[0052] 7-Methoxyindole-1-propyl isothiocyanate (I-09), red oily liquid, 1 H NMR (500MHz, CDCl3) δ7.20 (dd, J=8.0, 0.9Hz, 1H), 7.04-6.88 (m, 2H), 6.62 (dd, J=7.8, 0.8Hz, 1H), 6.43 ( d,J=3.1Hz,1H),4.50(t,J=6.4Hz,2H),3.93(s,3H),2.77(t,J=7.0Hz,2H),2.31(pd,J=6.8,2.1Hz,2H). 13 C NMR (125MHz, CDCl3) δ147.31,131.14,128.88,125.46,120.26,113.97,112.13,102.57,102.11,55.35,46.83,32.22,31.10.

[0053] 4-Benzyloxyindole-1-propyl isothiocyanate (I-10), yellow oily liquid, 1H NMR(500MHz, CDCl3)δ7.58(dd,J=6.6,1.5Hz,1H),7.33-7.22(m,4H),7.21-7.16(m,1H),7.07-6.94(m,3H),6 .78(d,J=5.2Hz,1H),5.15(s,2H),4.01(t,J=5.3Hz,2H),3.44(t,J=6.2Hz,2H),2.15(tt,J=6.2,5.3Hz,2H). 13 C NMR (125MHz, CDCl3) δ158.86,135.89,131.53,130.99,129.59,129.42,128.39 ,122.80,122.53,121.98,115.14,111.29,100.74,68.77,44.53,44.30,28.85.

[0054] 4-Chloroindole-1-propyl isothiocyanate (I-11), yellow oily liquid, 1 H NMR(500MHz, CDCl3)δ7.76-7.43(m,1H),7.36(dd,J=7.5,6.6Hz,1H),7.31-7.17(m,2H),6.6 9(d,J=5.3Hz,1H), 4.01(t,J=5.3Hz,2H), 3.44(t,J=6.2Hz,2H), 2.15(tt,J=6.2,5.3Hz,2H). 13 C NMR (125MHz, CDCl3) δ136.58,128.15,127.43,126.47,122.62,119.56,111.55,111.24,107.88,100.81,44.00,31.32,29.56.

[0055] 5-Chloroindole-1-propyl isothiocyanate (I-12), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.55(d,J=8.2Hz,1H),7.46(d,J=4.4Hz,1H),7.34(d,J=4.9Hz,1H),7.24(dd,J=8.2,2.2 Hz,1H),6.50(dd,J=5.0,2.0Hz,1H),3.98(t,J=5.3Hz,2H),3.44(t,J=6.2Hz,2H),2.15(tt,J=6.2,5.3Hz,2H). 13C NMR (125MHz, CDCl3) δ134.27,129.67,129.20,125.21,122.06,120.44,111.64,110.44,101.68,43.94,31.41,29.79.

[0056] 6-Chloroindole-1-propyl isothiocyanate (I-13), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.51 (d, J = 8.4Hz, 1H), 7.30 (s, 1H), 7.17-6.98 (m, 2H), 6.47 (d ,J=3.2Hz,1H),4.19(t,J=6.5Hz,2H),2.73(t,J=7.0Hz,2H),2.28(p,J=6.8Hz,2H). 13 C NMR (125MHz, CDCl3) δ136.26,128.40,127.94,127.29,122.19,120.49,111.69,109.25,102.39,43.79,30.71,30.00.

[0057] 7-Chloroindole-1-propyl isothiocyanate (I-14) Yellow oily liquid, 1 H-NMR (500MHz, CDCl3) δ7.51 (dd, J=7.8, 1.1Hz, 1H), 7.17 (dd, J=7.6, 1.0Hz, 1H), 7.08-6.98 (m, 2H), 6.51 (d, J = 3.2Hz, 1H), 4.65 (t, J = 6.6Hz, 2H), 2.84 (t, J = 7.0Hz, 2H), 2.40 (q, J = 6.8Hz, 2H). 13 CNMR (125MHz, CDCl3) δ132.10,130.99,130.55,123.75,120.61,120.12,116.35,111.72,102.62,46.24,32.25,30.79.

[0058] 6-Fluoroindole-1-propyl isothiocyanate (I-15) Yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.73-7.60(m,1H),7.41-7.22(m,2H),7.14(td,J=7.8,2.2Hz,1H),6. 51-6.32(m,1H),4.01(t,J=5.3Hz,2H),3.44(t,J=6.2Hz,2H),2.15(tt,J=6.2,5.3Hz,2H). 13C NMR (125MHz, CDCl3) δ157.55,137.06,130.99,128.91,125.45,121.63,109.81,104.04,95.61,44.30,44.15,28.85.

[0059] 4-Nitroindole-1-propyl isothiocyanate (I-16), yellow powder, 1 H NMR (500MHz, CDCl3) δ8.13 (dd, J=7.9, 0.8Hz, 1H), 7.69 (d, J=8.2Hz, 1H), 7.42-7 .22(m,3H),4.43(t,J=6.6Hz,2H),2.86(t,J=6.9Hz,2H),2.43(p,J=6.8Hz,2H). 13 C NMR (125MHz, CDCl3) δ140.63,137.97,131.89,122.76,120.98,117.79,115.94,111.32,102.82,44.17,30.55,30.08.

[0060] 5-Nitroindole-1-propyl isothiocyanate (I-17), yellow powder, 1 H NMR (500MHz, CDCl3) δ8.16-8.00(m,2H),7.91(d,J=9.1Hz,1H),7.35(d,J=5.1Hz,1H),6.56(dd ,J=5.1,2.1Hz,1H),3.98(t,J=5.3Hz,2H),3.44(t,J=6.2Hz,2H),2.15(tt,J=6.2,5.3Hz,2H). 13 C NMR (125MHz, CDCl3) δ141.73,138.70,130.76,127.88,118.44,117.60,111.45,109.10,104.90,44.21,30.59,30.05.

[0061] 6-Nitroindole-1-propyl isothiocyanate (I-18), yellow powder, 1H NMR (500MHz, CDCl3) δ8.49(d,J=2.2Hz,1H),8.01(dd,J=8.7,2.3Hz,1H),7.84(dd,J=8.6,1.1Hz,1H),7.35(d,J=5 .1Hz,1H),6.41(dd,J=5.1,1.1Hz,1H),4.01(t,J=5.3Hz,2H),3.44(t,J=6.2Hz,2H),2.15(tt,J=6.2,5.3Hz,2H). 13 C NMR (125MHz, CDCl3) δ144.32,136.29,132.51,130.99,129.02,120.59,118.18,106.08,105.18,44.33,44.30,28.85.

[0062] 7-Nitroindole-1-propyl isothiocyanate (I-19), yellow powder, 1 H NMR (500MHz, CDCl3) δ7.89-7.75(m,2H),7.55-7.39(m,1H),7.32(d,J=5.1Hz,1H),6.64 -6.46(m,1H),4.13(t,J=5.3Hz,2H),3.46(t,J=6.2Hz,2H),2.17(tt,J=6.3,5.3Hz,2H). 13 C NMR (125MHz, CDCl3) δ137.61,132.32,130.99,130.68,129.90,123.97,120.90,120.86,106.61,44.35,44.05,28.83.

[0063] 4-Bromoindole-1-propyl isothiocyanate (I-20), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.65 (dd, J=6.8, 1.3Hz, 1H), 7.42 (dd, J=7.6, 1.5Hz, 1H), 7.36-7.28 (m, 2H) ,6.68(d,J=5.5Hz,1H),4.01(t,J=5.3Hz,2H),3.44(t,J=6.2Hz,2H),2.15(tt,J=6.2,5.3Hz,2H). 13 CNMR (125MHz, CDCl3) δ136.15,129.32,128.20,122.93,122.72,115.19,111.28,108.45,102.50,44.05,31.33,29.58.

[0064] 6-Bromoindole-1-propyl isothiocyanate (I-21), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.54-7.44(m,2H),7.21(dd,J=8.5,1.6Hz,1H),7.04(d,J=3.1Hz,1H),6. 48(dd,J=3.2,0.8Hz,1H), 4.24(t,J=6.4Hz,2H), 2.76(t,J=7.0Hz,2H), 2.33(p,J=6.7Hz,2H). 13 CNMR (125MHz, CDCl3) δ136.66,128.23,127.58,123.08,122.54,115.62,112.17,111.54,102.45,43.76,30.70,29.96.

[0065] 7-Bromoindole-1-propyl isothiocyanate (I-22), yellow oily liquid, 1 H NMR (500MHz, CDCl3) δ7.57 (dt, J=6.9, 1.4Hz, 1H), 7.42 (dd, J=7.2, 1.2Hz, 1H), 7.37-7.16 ( m,2H),6.61-6.32(m,1H),3.99(t,J=5.3Hz,2H),3.44(t,J=6.2Hz,2H),2.23-2.11(m,2H). 13 C NMR (125MHz, CDCl3) δ132.19,132.04,130.77,127.26,121.00,120.71,111.71,103.47,102.53,45.82,32.26,30.74.

[0066] Example 2: Inhibitory activity of compounds of formula I-01 to 22 against four plant pathogens

[0067] The fungicidal activity of the compounds of formula I-01 to 22 was determined using the mycelial growth rate method. The test bacteria were apple tree rot pathogen, tomato gray mold pathogen, pepper phytophthora pathogen, and tobacco alternata pathogen, all of which were obtained from the College of Plant Protection, Northwest Agriculture and Forestry University.

[0068] Weigh each compound of Formula I-01-22 and prepare a 10,000 mg / L stock solution in methanol. Use a pipette to pipette each 10,000 mg / L stock solution into sterilized, cooled potato dextrose agar (PDA) medium. Mix thoroughly to prepare a 100 mg / L drug-coated culture medium. Pour 15 mL into 90 mm diameter Petri dishes, with four replicates for each drug. After the drug-coated culture medium condenses in the dishes, prepare drug-coated PDA plates. Methanol serves as a solvent control. A 4 mm diameter cake is punched along the edge of the colony on the cultured pathogen plate. This cake is inoculated onto the drug-coated and blank control PDA plates and incubated in the dark at 25°C. After the colonies on the blank control PDA plate have fully grown, measure the colony diameters of each treatment using the cross-hatch method and take the average value.

[0069] The mycelial growth inhibition rate was calculated using the following formula:

[0070]

[0071] The inhibitory effects of compounds I-01 to I-22 on four pathogens are shown in Table 2.

[0072] Table 2 Antibacterial activity test results of compounds I-01-22 against four pathogens at 100 mg / L

[0073]

[0074]

[0075]

[0076] In this test, at a concentration of 100 mg / L, compounds I-02, I-03, I-07, I-11, I-12, I-13, I-14, I-15, I-16, I-17, I-19, I-20, I-21, and I-22 showed an inhibition rate of greater than 80% (some compounds were higher than 90%) against tomato gray mold, and compounds I-11 and I-15 showed a 100% inhibition rate against tomato gray mold.

[0077] In this test, at a concentration of 100 mg / L, compounds I-07, I-08, I-11, I-12, and I-15 exhibited an inhibition rate of greater than 80% against Phytophthora capsici, and compound I-07 exhibited a 100% inhibition rate against Phytophthora capsici.

[0078] In this test, at a concentration of 100 mg / L, compounds I-01, I-02, I-04, I-08, I-09, I-11, I-14, and I-19 showed an inhibition rate of greater than 60% against tobacco brown spot pathogen.

[0079] In this test, at a concentration of 100 mg / L, all test compounds showed an inhibition rate of greater than 90% against apple tree rot pathogen; compounds I-02, I-03, I-04, I-05, I-07, I-08, I-09, I-11, I-12, I-13, I-14, I-15, I-17, I-18, I-19, I-20, I-21, and I-22 showed an inhibition rate of 100%.

[0080] Example 3: EC activity of some compounds of formula I against three plant pathogens 50 Value determination

[0081] The fungicidal activity of the compound of formula I was determined using the mycelial growth rate method. The test strains were apple tree rot pathogen, tomato gray mold pathogen, and pepper phytophthora.

[0082] Weigh each compound of Formula I and prepare a 10,000 mg / L stock solution with methanol. Use a pipette to pipette each of these 10,000 mg / L stock solutions and add them to sterilized, cooled potato dextrose agar (PDA) medium. After mixing, prepare drug-coated culture media at concentrations of 100, 50, 25, 12.5, 6.25, 3.12, 1.56, 0.780, and 0.390 mg / L, respectively. Pour 15 mL of the drug-coated culture media into 90 mm diameter Petri dishes, with four replicates for each agent. After the drug-coated culture media in the dishes condenses, prepare drug-coated PDA plates. Methanol is used as a solvent blank control. A 4 mm diameter cake is punched along the edge of the colony on the cultured pathogen plate. This cake is inoculated onto the drug-coated and blank PDA plates, respectively, and incubated in the dark at 25°C in an incubator. After the colonies in the blank control PDA plate have grown fully, the diameters of the colonies in each treatment are measured by the cross method and the average value is taken.

[0083] The mycelial growth inhibition rate was calculated using the following formula:

[0084]

[0085] Table 3 Regression equations and EC values ​​of the antibacterial toxicity of the four compounds against the three pathogens 50 Measurement results

[0086]

[0087] In this test, the EC of compounds I-07, I-11, I-12, and I-15 against Botrytis cinerea 50 The values ​​are 2.12mg / L, 0.64mg / L, 2.08mg / L, and 9.28mg / L respectively.

[0088] In this test, compounds I-07, I-11, I-12, and I-15 had EC 50 The values ​​are 47.30mg / L, 9.83mg / L, 13.44mg / L, and 18.93mg / L respectively.

[0089] In this test, the EC values ​​of compounds I-07, I-11, I-12, and I-15 against apple rot pathogens were 50 The values ​​are 7.60mg / L, 3.36mg / L, 4.81mg / L, and 7.89mg / L respectively.

[0090] The results of Example 3 show that compounds I-07, I-11, I-12, and I-15 have a certain inhibitory effect on the mycelial growth of tomato gray mold, pepper phytophthora, and apple rot pathogens, and their EC 50 The values ​​were all less than 20 mg / L. Among them, the EC values ​​of compounds I-11 and I-12 on the mycelial growth of tomato gray mold pathogen were 50 The value is less than 2.1 mg / L, which has an excellent inhibitory effect. In order to verify its activity, the efficacy of compounds I-11 and I-12 on tomato gray mold was further studied.

[0091] Example 4: Potted efficacy test of compounds I-11 and I-12 against tomato gray mold

[0092] The protective efficacy of compounds I-11 and I-12 against tomato gray mold was verified using the pot culture method.

[0093] When the tomato plants have grown to 2 to 4 true leaves, select plants with uniform growth and use an inoculation needle to inoculate the side of the activated tomato gray mold cake with mycelium on the treated leaves. Spray the test agent evenly on the front and back of the leaves until they are moistened and no liquid drips. The protective effect test is inoculated 4 hours after the test agent spray treatment, and the therapeutic effect test is inoculated 6 hours before the test agent treatment. After inoculation (piercing small holes on the plant leaves), wrap the leaves with a small self-sealing bag to keep them moist. Each treatment is repeated 3 times, with 3 pots of plants per repetition, and cultured for 2-3 days. Each drug treatment includes clean water (blank control), compounds I-11 and 12 (200 and 50 μg / mL, drug treatment), and the incidence of the blank control is investigated. The diameter of the lesions is measured by the cross-cross vertical method, and the average value is taken in millimeters (mm). The lesion area and the control effect (protective effect or therapeutic effect) are calculated as follows.

[0094]

[0095]

[0096] Table 4 The pot control efficacy of two compounds on tomato gray mold

[0097]

[0098] In this test, at a concentration of 200 mg / L, compound I-11 showed a protective effect of 79.51% against tomato gray mold, and I-12 showed a protective effect of 86.34% against tomato gray mold.

[0099] The preferred embodiments of the present disclosure are described in detail above. However, the present disclosure is not limited to the specific details of the above embodiments. Within the technical concept of the present disclosure, various simple modifications can be made to the technical solutions of the present disclosure, and these simple modifications all fall within the scope of protection of the present disclosure.

[0100] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present disclosure will not further describe various possible combinations.

[0101] In addition, the various embodiments of the present disclosure may be arbitrarily combined, and as long as they do not violate the concept of the present disclosure, they should also be regarded as the contents disclosed by the present disclosure.

Claims

1. An indole isothiocyanate compound, characterized in that: The structural formula of the compound is shown in Formula I; Formula I wherein the R group is selected from 2-CH3, 3-CH3, 5-CH3, 7-CH3, 2,3-CH3, 2,5-CH3, 4-OCH3, 6-OCH3, 7-OCH3, 4-benzyloxy, 4-Cl, 5-Cl, 6-Cl, 7-Cl, 6-F, 4-NO2, 5-NO2, 6-NO2, 7-NO2, 4-Br, 6-Br or 7-Br.

2. The method for preparing the indole isothiocyanate compound according to claim 1, wherein The method comprises the following steps: Step 1: reacting the compound represented by Formula II with 1,3-dibromopropane in a first organic solvent at room temperature in the presence of a basic salt to obtain a compound represented by Formula IV; ， ； Step 2: reacting the compound represented by formula IV with sodium thiocyanate in a second organic solvent at 45-55° C., then heating to 60-85° C. and continuing the reaction to obtain the compound represented by formula I.

3. The method for preparing the indole isothiocyanate compound according to claim 2, wherein: The first organic solvent is selected from acetonitrile or N , N -dimethylformamide; the alkaline salt is selected from potassium hydroxide or sodium hydroxide.

4. The method for preparing the indole isothiocyanate compound according to claim 2, wherein: The molar ratio of the compound represented by formula II, the basic salt and 1,3-dibromopropane is 1:1:(1-2.5).

5. The method for preparing the indole isothiocyanate compound according to claim 2, wherein: The reaction time of step 1 is 6 to 8 hours.

6. The method for preparing the indole isothiocyanate compound according to claim 2, wherein: The second organic solvent is selected from ethanol.

7. The method for preparing the indole isothiocyanate compound according to claim 2, wherein: The molar ratio of the compound represented by formula IV to sodium thiocyanate is 1:(1-2.5); the reaction time in step 2 is 5-8 hours; and the reaction time at 60-85° C. is 4-8 hours.

8. Use of the indole isothiocyanate compound according to claim 1 in preparing a botanical fungicide.

9. Use of the indole isothiocyanate compound according to claim 1 in the preparation of a fungicide for preventing and treating tomato gray mold, apple rot, pepper phytophthora or tobacco brown spot.

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