Isoquinoline-3-acylhydrazone aromatic cycloalkane compound and application thereof in prevention and control of plant diseases

Abstract

The invention provides an isoquinoline-3-acylhydrazone aromatic cycloalkene compound and application thereof in plant disease control. The structural general formulas of the isoquinoline-3-acylhydrazone aromatic cycloalkene compound are shown as a formula 1, a formula 2 and a formula 3: imgabs0 # R1 is one of hydrogen atoms, hydroxyl groups, fluorine atoms, chlorine atoms, bromine atoms, trifluoromethyl, amino groups, sulfydryl groups, C1-12 alkyl groups, C1-6 alkoxy groups, C1-6 alkyl amino groups and C1-6 alkyl sulfydryl groups. The isoquinoline-3-acylhydrazone aromatic cycloalkane compound disclosed by the invention is applied to prevention and treatment of plant fungal diseases caused by fungal germs in agriculture. The raw materials of the isoquinoline-3-acylhydrazone aromatic ring / naphthenic compound are easy to obtain, the synthesis method is simple and practical, the cost is low, the compound has an excellent inhibition effect on plant fungal diseases, the structure is novel, and research results have positive significance on creation of new pesticides.

Description

Technical Field

[0001] The invention relates to the technical field of pesticides, and in particular to isoquinoline-3-acylhydrazone aromatic ring cycloalkane compounds and applications thereof in plant disease prevention and control. Background Art

[0002] Plant fungal diseases have always been a difficult problem in production control, such as rice blast, sheath blight, wheat head blight, stripe rust, cotton wilt, rapeseed sclerotinia, etc., which seriously affect the yield and quality of crops. Chemical control is an important means of pest control. However, the current control agents such as triazoles, strobilurins, succinate dehydrogenase inhibitors, etc., have caused serious drug resistance due to long-term and large-scale use, which in turn threatens the quality and safety of agricultural products and environmental risks. Therefore, it is urgent to create novel, efficient, low-toxic green fungicides to control the increasingly serious plant diseases.

[0003] Isoquinoline-3-carboxylic acid is an isoquinoline compound. The research team discovered for the first time that the compound has a broad-spectrum fungicidal activity against plant pathogenic bacteria. On this basis, they applied for an invention patent "Application of isoquinoline-3-carboxylic acid in the prevention and control of plant bacterial diseases (application number: 202310826994.1)". At the same time, the compound was structurally modified and it was found that isoquinoline compounds containing acylhydrazone bissulfone groups have strong fungicidal activity against plant pathogenic bacteria (isoquinoline-3-acylhydrazone bissulfone compounds and their preparation methods and applications, application number: 202311550250.8). However, this type of structure has poor fungicidal effect on plant pathogenic fungi. In order to create isoquinoline compounds with novel structure and higher fungicidal activity, the research team used isoquinoline-3-carboxylic acid as the lead skeleton and adopted the pharmacophore active splicing technology to introduce acylhydrazone aromatic ring and acylhydrazone cycloalkyl group into the 3-carboxyl group of its active site. They designed and synthesized new isoquinoline compounds containing acylhydrazone aromatic ring / cycloalkyl group, which have excellent fungicidal activity against a variety of plant pathogenic fungi such as tomato gray mold. Summary of the invention

[0004] Based on the prior art, the technical problem to be solved by the present invention is to provide isoquinoline-3-acylhydrazone aromatic ring cycloalkane compounds and their application in plant disease prevention and control to solve the above problems.

[0005] The technical solution of the present invention:

[0006] Isoquinoline-3-acylhydrazone aromatic ring cycloalkane compound, characterized in that its general structural formula is as shown in Formula 1, Formula 2 or Formula 3:

[0007]

[0008] In the formula, R1 is a hydrogen atom, a hydroxyl group, a fluorine atom, a chlorine atom, a bromine atom, a trifluoromethyl group, an amino group, a mercapto group, a C1-12 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylamino, C 1-6 One of the alkylthio groups;

[0009] Further, in Formula 1, R2 is C 3-10 Cycloalkyl, halogen-substituted C 3-10 Cycloalkyl, C 1-4 Hydrocarbon-substituted C 3-10 Cycloalkyl, C 1-4 Hydroxyl substituted C 3-10 A cycloalkyl group.

[0010] Furthermore, in Formula 1, R2 is one of cyclopropane, cyclobutane, cyclopentane, cyclohexane, and cycloheptane.

[0011] Furthermore, in Formula 2 and Formula 3, R2 and R3 are C 1-4 Hydrocarbon-substituted phenyl, C 1-4 phenyl substituted with alkoxy, benzyl substituted with halogen, phenyl substituted with nitro, phenyl substituted with cyano, phenyl substituted with ester, pyridyl substituted with halogen, C 1-4 Hydrocarbyl-substituted pyridyl, C 1-4 A type of pyridyl substituted with an alkoxy group.

[0012] Compared with the prior art, the present invention has the following beneficial effects:

[0013] (1) The acylhydrazone cycloalkane compounds of the present invention have high fungicidal activity, especially against tomato gray mold and mango anthracnose, and the activity increases with the extension of the treatment time. The protective effect is 65.03% at a test concentration of 100 μg / mL on the 6th day after treatment.

[0014] (2) The acylhydrazone cycloalkane compounds of the present invention have high fungicidal activity against mango anthracnose, with an inhibition rate ranging from 60.46% to 71.79%, which is better than the control agent boscalid.

[0015] (3) The isoquinoline-3-acylhydrazone cycloalkane compounds of the present invention have novel structures, readily available raw materials, simple and practical synthesis methods, low costs, and have excellent inhibitory effects on plant fungal diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 :Z14 hydrogen spectrum

[0017] In the figure, the horizontal axis f1 refers to the chemical shift and represents the position of the spectrum peak. DETAILED DESCRIPTION

[0018] In order to better understand the technical content of the present invention, specific examples are provided below to further illustrate the present invention. The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.

[0019] Unless otherwise specified, the materials, reagents, etc. used in the embodiments of the present invention can be obtained from commercial sources.

[0020] The isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds in the following examples were synthesized by the Green Pesticide Creation and Application Research Group of the Institute of Environment and Plant Protection, Chinese Academy of Tropical Agricultural Sciences and tested for fungicidal activity.

[0021] Example 1

[0022] Compound was prepared and named as Compound 1.

[0023]

[0024] 4-Cyanobenzylacetic acid (2.0mmol) was added to a round-bottom flask, the system was replaced with an inert environment, 10mL of dry DMF (dimethylformamide) was added, the system was placed in a -30°C low-temperature bath, and a solution of lithium bistrimethylsilylamide (8.0mmol) in THF (tetrahydrofuran) was slowly added dropwise. 3-trifluoromethylbenzoic acid methyl ester (2.02mmol) was added dropwise to the system 10 minutes after the addition was completed. The system temperature was maintained at -30°C, and the temperature was slowly raised to room temperature after 2 hours to react for 8 hours. After TLC (thin layer chromatography) monitoring, a saturated ammonium chloride solution was slowly added dropwise to the system to quench the reaction, extracted with ethyl acetate, washed with water twice, and the organic phase was dried and desolventized to obtain a crude product, which was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 10:1 (V:V) Rf = 0.56) to obtain a light yellow solid compound 1 with a yield of 87.8%.

[0025]

[0026] Isoquinoline-3-hydrazide (2.0 mmol) was added to a reaction tube, and a methanol:n-hexane 10:1 mixed solvent (11 ml) was added. After stirring, compound 1 (2.0 mmol) was added, and 3-5 drops of trifluoroacetic acid were added. The reaction was heated to reflux and reacted for 6 hours, and the reaction was monitored by TLC. After the reaction was completed, the solvent was removed and recrystallized with methanol or purified by column chromatography (eluent: petroleum ether: ethyl acetate = 2:1 (V:V)) to obtain a white solid compound, which was named Z1 with a yield of 81.3%.

[0027] 1H NMR (400MHz, DMSO-d6) δ11.55(s,1H),9.37(s,1H),8.68(s,1H),8.31-8.17(m,4H),7.91(t,J=7.5Hz,1 H),7.87-7.77(m,2H),7.71(t,J=7.9Hz,1H),7.41(d,J=8.2Hz,2H),7.34(d,J=8.3Hz,2H),4.46(s,2H). 13 C NMR(100MHz,DMSO)δ160.1,152.7,151.7,142.4,138.1,135.3,134.0,131.7(*2),130.9,130.1(*2 ),129.9,129.6,129.5,129.3,128.9(*2),128.1,127.9,126.1,125.4,123.0,122.7,120.7,31.7.

[0028] Example 2

[0029] Compound was prepared and named as Z2.

[0030] The preparation method of compound Z2 is the same as the synthesis method of compound Z1, light yellow solid, 1 H NMR (400MHz, DMSO-d6) δ11.48(s,1H),9.35(s,1H),8.66(s,1H),8.24(t,J=8.3H z,2H),7.97(d,J=8.7Hz,2H),7.94-7.79(m,4H),7.57-7.46(m,4H),4.51(s,2H). 13 C NMR (100MHz, DMSO) δ160.0,152.5,151.7,142.5,141.2,135.8,135.3,134.6,132.8(*2),131. 7,129.6,129.5,129.4(*2),128.7(*2),128.6(*2),128.1,127.9,120.6,118.6,109.8,32.5.

[0031] Example 3

[0032] Compound was prepared and named Z3.

[0033] The preparation method of compound Z3 is the same as the synthesis method of compound Z1, white solid, 1H NMR (400MHz, DMSO-d6) δ11.43(s,1H),9.35(s,1H),8.66(s,1H),8.24(t,J=8.9Hz,2H),7.90(t,J=7.6Hz,1H),7.87-7.79(m ,4H),7.73(d,J=7.7Hz,1H),7.50(d,J=8.3Hz,2H),7.35(t,J=7.7Hz,1H),7.27(d,J=7.8Hz,1H),4.50(s,2H),2.37(s,3H). 13 C NMR(100MHz,DMSO)δ159.9,153.9,151.7,142.6,141.5,137.8,137.0,135.3,132.8(*2),131.6,13 0.5,129.6,129.4,129.3(*2),128.5,128.1,127.9,127.2,124.2,120.5,118.6,109.7,32.7,21.0.

[0034] Example 4

[0035] Compound was prepared and named Z4.

[0036] The preparation method of compound Z4 is the same as the synthesis method of compound Z1, yellow solid, 1 H NMR (400MHz, DMSO-d6) δ11.53(s,1H),9.36(d,J=4.3Hz,1H),8.67(s,1H),8.24(t,J=8.4Hz,2H),7.96(s,1H),7.91(t,J=7.5Hz ,1H),7.83(dd,J=12.9,7.7Hz,3H),7.67(d,J=14.0Hz,1H),7.50(d,J=8.2Hz,2H),7.35(t,J=9.2Hz,1H),4.54(d,J=5.7Hz,2H). 13 C NMR (100MHz, DMSO) δ163.8,160.2,151.7,140.9,140.5,135.3,134.5,132.8,131.7, 129.7,129.5,129.4,129.0,128.1,127.9,125.4,120.8,118.5,110.1,109.8,32.3.

[0037] Example 5

[0038] Compound was prepared and named Z5.

[0039] The preparation method of compound Z5 is the same as the synthesis method of compound Z1, white powder solid, 1 H NMR (400MHz, DMSO-d6) δ11.50(s,1H),9.35(s,1H),8.67(s,1H),8.24(t,J=8.0Hz,2H),8.14(t,J=1.9Hz,1H),7.96 -7.87(m,2H),7.87-7.78(m,3H),7.64(d,J=7.9Hz,1H),7.50(d,J=8.1Hz,2H),7.42(t,J=7.9Hz,1H),4.52(s,2H). 13 C NMR(100MHz,DMSO)δ160.1,152.1,151.7,142.4,141.1,139.3,135.3,132.8(*2),132.4,131.6, 130.8,129.6,129.5,129.4(*2),129.1,128.1,127.9,126.0,122.1,120.7,118.5,109.8,32.5.

[0040] Example 6

[0041] Compound was prepared and named Z6.

[0042] The preparation method of compound Z6 is the same as the synthesis method of compound Z1, white solid, 1 H NMR (400MHz, DMSO-d6) δ11.50(s,1H),9.35(s,1H),8.67(s,1H),8.24(t,J=8.0Hz,2H),8.14(t,J=1.9Hz,1H),7.91(dd,J=12. 8,7.1Hz,2H),7.83(dd,J=11.9,8.2Hz,3H),7.64(d,J=7.9Hz,1H),7.50(d,J=8.1Hz,2H),7.42(t,J=7.9Hz,1H),4.52(s,2H). 13 C NMR(100MHz,DMSO)δ160.1,152.1,151.7,142.4,141.1,139.3,136.3,132.8(*2),132.4,131.6, 130.8,129.6(*2),129.5,129.4,129.1,128.1,127.9,125.5,122.1,120.7,118.0,109.8,32.5.

[0043] Example 7

[0044] Compound was prepared and named Z7.

[0045] The preparation method of compound Z7 is the same as the synthesis method of compound Z1, orange-yellow solid, 1 H NMR (400MHz, DMSO-d6) δ11.53(s,1H),9.37(s,1H),8.68(s,1H),8.25(t,J=8.2Hz,2H),8.00-7.88(m, 2H),7.88-7.78(m,3H),7.73-7.62(m,1H),7.52(d,J=8.4Hz,2H),7.36(t,J=7.8Hz,1H),4.54(s,2H). 13 C NMR(100MHz,DMSO)δ161.4,160.2,151.7,151.2,150.8,142.3,141.0,135.3,134.6,132.9(*2), 131.7,129.7,129.5,129.4(*2),129.0,128.1,127.9,125.4,120.8,118.6,110.1,109.8,32.3.

[0046] Example 8

[0047] Compound was prepared and named Z8.

[0048] The preparation method of compound Z8 is the same as the synthesis method of compound Z1, white solid, 1 H NMR (400MHz, DMSO-d6) δ11.55(s,1H),9.37(s,1H),8.68(s,1H),8.31-8.17(m,4H),7.64(d,J=7.9Hz,1H) ,7.50(d,J=8.1Hz,2H),7.42(t,J=7.9Hz,1H),7.41(d,J=8.2Hz,2H),7.34(d,J=8.3Hz,2H),4.46(s,2H). 13 C NMR(100MHz,DMSO)δ160.1,152.7,151.7,142.4,138.1,135.3,134.0,131.5(*2),130.9,130.1 (*2),129.9,129.6,129.5,129.3,128.9(*2),128.1,127.6,126.1,125.4,124.0,122.3,31.7.

[0049] Example 9

[0050] Compound was prepared and named Z9.

[0051] The preparation method of compound Z9 is the same as the synthesis method of compound Z1, light yellow solid, 1 H NMR (400MHz, DMSO-d6) δ11.50(s,1H),9.35(s,1H),8.67(s,1H),8.24(t,J=8.0Hz,2H),8.14(t,J=1.9Hz,1H ),7.91(d,J=7.1Hz,1H),7.64(dt,J=7.9Hz,4H),7.50(d,J=8.1Hz,2H),7.42(t,J=7.9Hz,2H),4.52(s,2H). 13 C NMR(100MHz,DMSO)δ160.1,152.1,151.7,142.4,141.1,139.3,136.3,132.5(*2),132.4,131 .6,130.8,129.8(*2),129.5,129.4,129.1,128.1,127.9,125.5,122.1,120.0,109.8,32.5.

[0052] Example 10

[0053] Compound was prepared and named Z10.

[0054] The preparation method of compound Z10 is the same as the synthesis method of compound Z1, white solid, 1 H NMR (400MHz, DMSO-d6) δ11.43(s,1H),9.35(s,1H),8.66(s,1H),8.24(t,J=8.9Hz,2H),7.90(t,J=7.6Hz,2H),7.50(d,J=8.3 Hz,2H),7.50(d,J=8.1Hz,2H),7.42(t,J=7.9Hz,2H),7.35(t,J=7.7Hz,1H),7.27(d,J=7.8Hz,1H),4.50(s,2H),2.37(s,3H). 13C NMR(100MHz,DMSO)δ159.9,153.9,151.7,142.6,141.5,137.8,137.0,135.3,132.8(*2),131.6 ,130.5,129.6,129.4,129.3(*2),128.5,128.1,127.9,127.2,124.2,120.5,109.7,32.7,21.0.

[0055] Embodiment 11

[0056] Compound was prepared and named Z11.

[0057] The preparation method of compound Z11 is the same as the synthesis method of compound Z1, light yellow solid, 1 H NMR (400MHz, DMSO-d6) δ11.53(s,1H),9.36(d,J=4.3Hz,1H),8.67(s,1H),8.24(t,J=8.4Hz,2H),7.96(s,1H),7.91(t,J=7.5Hz ,1H),7.83(dd,J=12.9,7.7Hz,3H),7.64(d,J=7.9Hz,1H),7.50(d,J=8.1Hz,2H),7.42(t,J=7.9Hz,1H),4.54(d,J=5.7Hz,2H). 13 C NMR (100MHz, DMSO) δ163.8,160.2,151.7,140.9,140.5,135.3,134.5,132.8,131 .7,129.7,129.5,129.4,129.0,128.1,127.9,125.4,120.8,110.1,109.8,32.3.

[0058] Example 12

[0059] Compound was prepared and named Z12.

[0060] The preparation method of compound Z12 is the same as the synthesis method of compound Z1, light yellow solid, 1 H NMR (400MHz, DMSO-d6) δ11.48(s,1H),9.35(s,1H),8.66(s,1H),8.24(t,J=8.3H z,2H),7.97(d,J=8.7Hz,2H),7.94-7.79(m,4H),7.57-7.46(m,4H),4.51(s,2H). 13C NMR(100MHz,DMSO)δ160.0,152.5,151.7,142.5,141.2,135.8,135.3,134.6,132.8(*2),1 31.7,129.6,129.5,129.4(*2),128.7(*2),128.6(*2),128.1,127.9,120.6,109.8,32.5.

[0061] Example 13

[0062] Compound was prepared and named Z13.

[0063]

[0064] Add isoquinoline-3-hydrazide (2.0 mmol) to a reaction tube, add methanol:n-hexane 10:1 mixed solvent (11 ml), stir evenly, add cycloheptanone (2.0 mmol), and drop 3-5 drops of trifluoroacetic acid. Heat the reaction to reflux for 6 hours and monitor the reaction by TLC. After the reaction, remove the solvent and use methanol for recrystallization or column chromatography purification (eluent: petroleum ether: ethyl acetate = 2:1 (V:V)) to obtain a white solid compound, which is named Z13 with a yield of 83.6%.

[0065] 1 H NMR(400MHz,Chloroform-d)δ10.93(s,1H),9.12(s,1H),8.71(s,1H),8.01(d,J=8.1Hz,1H),7.96(d,J=8.1Hz,1H), 7.75(t,J=7.5Hz,1H),7.69(t,J=6.9Hz,1H),2.74-2.64(m,2H),2.64-2.56(m,2H),1.83(s,2H),1.70-1.62(m,6H). 13 C NMR (100MHz, CDCl3) δ164.1,160.5,151.2,143.4,136.1,131.3,129.9,129.1,128.2,127.8,121.1,37.3,30.5,30.4(*2),27.6,24.5.

[0066] Embodiment 14

[0067] Compound and named it as compound Z14.

[0068] The preparation method of compound Z14 is the same as the synthesis method of compound Z13, white solid, 1H NMR (400MHz, Chloroform-d) δ10.95 (s, 1H), 9.05 (s, 1H), 8.61 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.69-7.57 (m, 2H), 2.43 (dt, J = 9.6, 6.2 Hz, 4H), 1.69 (d, J = 3.4 Hz, 4H), 1.60 (d, J = 4.8 Hz, 2H). 13C NMR (100MHz, CDCl3) δ161.8,160.4,151.0,143.1,135.8,131.1,129.6,128.9,127.9,127.6,120.8,35.6,26.9,26.8,26.0,25.5.

[0069] Embodiment 15

[0070] Compound was prepared and named Z15.

[0071] The preparation method of compound Z15 is the same as the synthesis method of compound Z13, white solid, 1 H NMR (400MHz, Chloroform-d) δ10.61(s,1H),9.06(s,1H),8.64(s,1H),7.95(d,J=8.1Hz,1H),7.89(d,J=8.0Hz,1H),7.73-7. 67(m,1H),7.63(t,J=7.5Hz,1H),2.56(t,J=7.1Hz,2H),2.44(t,J=7.4Hz,2H),1.88(p,J=6.9Hz,2H),1.76(p,J=6.8Hz,2H). 13 C NMR (100MHz, CDCl3) δ168.0,160.3,151.1,143.1,135.9,131.2,129.8,129.0,128.0,127.7,121.0,33.6,27.7,24.8,24.7.

[0072] Example 16

[0073] Compound was prepared and named Z16.

[0074] The preparation method of compound Z16 is the same as the synthesis method of compound Z13, white solid, 1H NMR(400MHz,Chloroform-d)δ10.51(s,1H),9.02(s,1H),8.61(s,1H),7.93(d,J=8.1Hz,1H),7.85(d, J=8.1Hz,1H),7.67(t,J=7.5Hz,1H),7.61(t,J=7.6Hz,1H),3.10-2.94(m,4H),2.03(p,J=8.0Hz,2H). 13 C NMR (100MHz, CDCl3) δ160.8,160.1,151.0,142.9,135.8,131.1,129.7,129.0,128.0,127.6,121.0,34.2,31.8,13.8.

[0075] Embodiment 17

[0076] Compound was prepared and named Z17.

[0077] The preparation method of compound Z17 is the same as the synthesis method of compound Z13, white solid, 1 H NMR (400MHz, DMSO-d6) δ11.18(s,1H),9.10(s,1H),8.67(s,1H),8.23(s,1H),7.98(d,J=8.0Hz,1H),7.91 (d,J=8.1Hz,1H),7.76-7.63(m,3H),7.53(d,J=7.6Hz,1H),7.25(t,J=7.6Hz,1H),7.17(d,J=7.6Hz,1H). 13 C NMR (100MHz, DMSO) δ160.7,151.1,148.9,142.8,138.4,135.9,133.7,131.4,131.3,129.5,129.2,128.4,128.1,127.1,126.7,124.5,120.3.

[0078] Embodiment 18

[0079] Compound was prepared and named Z18.

[0080] The preparation method of compound Z18 is the same as the synthesis method of compound Z13, white solid, 1H NMR (400MHz, Chloroform-d) δ11.20(s,1H),9.15(s,1H),8.73(s,1H),8.32(s,1H),8.09-7.97(m,2H),7.87-7.70(m,4H),7.10(t,J=8.6Hz,2H). 13 C NMR (100MHz, CDCl3) δ165.5,163.1,160.8,151.3,147.6,142.9,136.1,131.4,130.1,129.9,129.8,129.4,128.4,127.9,121.5,116.1,115.9.

[0081] Embodiment 19

[0082] Compound was prepared and named Z19.

[0083] The preparation method of compound Z19 is the same as the synthesis method of compound Z13, white solid, 1 H NMR(400MHz,DMSO-d6)δ11.21(s,1H),9.13(s,1H),8.70(s,1H),8.28(s,1H),8.07-7.93(m, 2H),7.80-7.66(m,2H),7.44(s,1H),7.29(d,J=4.8Hz,2H),7.00-6.91(m,1H),3.84(s,3H). 13 C NMR (100MHz, DMSO) δ160.7,160.0,151.2,148.8,142.8,136.0,135.3,131 .3,130.0,129.7,129.3,128.2,127.8,121.4,121.3,117.5,111.3,55.6.

[0084] Embodiment 20

[0085] Compound was prepared and named Z20.

[0086] The preparation method of compound Z20 is the same as the synthesis method of compound Z13, white solid, 1H NMR (400MHz, DMSO-d6) δ11.18(s,1H),9.10(s,1H),8.67(s,1H),8.23(s,1H),7.98(d,J=8.0Hz,1H),7.91(d,J= 8.1Hz,1H),7.76-7.63(m,3H),7.53(d,J=7.6Hz,1H),7.25(t,J=7.6Hz,1H),7.17(d,J=7.6Hz,1H),2.33(s,3H). 13 C NMR (100MHz, DMSO) δ160.7,151.1,148.9,142.8,138.4,135.9,133.7,131 .4,131.3,129.9,129.2,128.5,128.1,128.1,127.7,125.5,121.3,21.2.

[0087] Embodiment 21

[0088] Compound was prepared and named Z21.

[0089] The preparation method of compound Z21 is the same as the synthesis method of compound Z13, white solid, 1 H NMR(400MHz,Chloroform-d)δ11.40(s,1H),11.04(s,1H),9.18(s,1H),8.70(s,1H),8.48(s,1H),8.12-7.99(m ,2H),7.86-7.71(m,2H),7.16(d,J=8.6Hz,1H),6.57(d,J=2.4Hz,1H),6.49(dd,J=8.5,2.5Hz,1H),3.83(s,3H). 13 C NMR (100MHz, CDCl3) δ163.4,160.9,151.3,136.2,132.2,131.5,129.9,129.4,128.4,127.9,121.4,113.2,107.3,101.7,55.6.

[0090] Embodiment 22

[0091] Compound was prepared and named Z22.

[0092] The preparation method of compound Z22 is the same as the synthesis method of compound Z13, white solid, 1H NMR (400MHz, DMSO-d6) δ12.43(s,1H),9.40(s,1H),8.64(d,J=16.1Hz,2H),8.22(dd,J=16.8,8.0Hz,2H),7.95-7.77(m,2H),7.69(s,2H),7.58(s,1H). 13 C NMR (100MHz, DMSO) δ160.9,151.6,145.9,138.1,135.3,134.6,131.5,129.5,129.1,128.1,127.8,125.3(*2),121.0.

[0093] Embodiment 23

[0094] Compound was prepared and named Z23.

[0095] The preparation method of compound Z23 is the same as the synthesis method of compound Z13, yellow solid, 1 H NMR (400MHz, DMSO-d6) δ12.42(s,1H),9.41(s,1H),8.84-8.62(m,2H),8.23(s,2H),7.96-7.72(m,6H). 13 CNMR(100MHz,DMSO)δ160.9,151.6,147.3,143.0,138.4,135.3,131.5,129.4,128.0,127.8,127.7,125.7,121.0.

[0096] Embodiment 24

[0097] Compound was prepared and named Z24.

[0098] The preparation method of compound Z24 is the same as the synthesis method of compound Z13, yellow solid, 1 H NMR(400MHz,DMSO-d6)δ12.50(s,1H),9.40(s,1H),8.87(s,1H),8.66(s,1H),8.3 0-8.13(m,2H),7.93-7.74(m,3H),7.58(d,J=10.0Hz,1H),7.47(d,J=8.5Hz,1H). 13C NMR (100MHz, DMSO) δ161.7,160.9,159.1,151.5,143.0,140.8,140.8,135.3,131.4,129.4, 129.4,128.2,128.1,128.0,127.8,127.8,123.5,123.4,121.7,121.6,120.9,119.4,119.2.

[0099] Embodiment 25

[0100] Compound was prepared and named as Z25.

[0101] The preparation method of compound Z25 is the same as the synthesis method of compound Z13, white solid, 1 H NMR (400MHz, DMSO-d6) δ12.26(s,1H),9.43(s,1H),8.68(s,1H),8.63(s,1H),8.24(dd,J=14.7,8.3Hz ,2H),7.91-7.85(m,1H),7.85-7.78(m,1H),6.87(d,J=2.3Hz,2H),6.56(t,J=2.3Hz,1H),3.79(s,6H). 13 C NMR (100MHz, DMSO) δ160.6,160.6,151.5,148.9,143.1,136.4,135.3,131.4,129.4,129.3,128.0,127.8,120.7,104.9,102.3,55.3.

[0102] Experiment 1: Determination of fungicidal activity of isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds against plant pathogenic fungi

[0103] The plant pathogenic bacteria tested include: Botrytis cinerea, Colletotrichum gloeosporioides, Rhizoctonia solani, Fusarium graminearum, Phytophthora capsici, and Lasiodiplodia pseudotheobromae. The preservation institution of the plant pathogenic bacteria tested is the Green Pesticide Creation and Application Research Group of the Institute of Environment and Plant Protection, Chinese Academy of Tropical Agricultural Sciences.

[0104] Bactericidal activity experimental method: The bactericidal activity of the compounds prepared in Example 3-12 against plant pathogenic fungi was tested (see Table 1). The present invention uses the growth rate method to evaluate the bactericidal activity of isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds against 6 plant fungi such as tomato gray mold. The test method refers to the method of Fang Zhongda (Fang Zhongda. Plant Pathology Research Methods. Beijing: China Agriculture Press, 1998). The mycelial growth was carefully observed and recorded under an inverted microscope (400X). The determination of the inhibitory effect of isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds on the mycelial growth of plant pathogenic fungi was 100 μg / mL as the screening concentration, and the pathogens with higher inhibitory activity were subjected to tissue method determination tests to verify their activity strength. Each of the above treatments was repeated 3 times (3 culture dishes), with blank culture medium as the control.

[0105] Mycelium growth inhibition rate (%) = control colony diameter - treated colony diameter (control colony diameter) / control colony diameter × 100%

[0106] Experimental results: The fungicidal activity of 25 isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds against tomato gray mold, rice sheath blight, wheat fusarium, mango anthracnose, pepper phytophthora and citrus acid rot was tested. The results showed that the fungicidal activity of compounds Z1-Z10 containing acylhydrazone biphenyl groups was not high overall, and the inhibition rate was between 25% and 50% at a test concentration of 100 μg / mL; the fungicidal activity trend of phenylhydrazone compounds Z17-Z25 was similar to that of acylhydrazone biphenyl compounds. The compounds are similar; the acylhydrazone cycloalkane compounds Z13-Z16 have high fungicidal activity, especially against tomato gray mold, the inhibition rates at the tested concentration of 100 μg / mL are 87.68%, 90.50%, 85.14% and 86.43%, respectively; at the same time, this type of compounds also has high fungicidal activity against mango anthracnose, and the inhibition rates are 60.46%, 71.79%, 57.86% and 62.86%, respectively, which are better than the control agent boscalid.

[0107] Table 1 Fungicidal activity of the compounds prepared in Examples 1-25 against plant pathogenic fungi

[0108]

[0109]

[0110] Experiment 2: Tissue assay of compound Z-14 against tomato gray mold

[0111] Test materials: grapes, the grape variety is commercially available Sunshine Rose.

[0112] Pot test method: The in vivo effect of the compound on Botrytis cinerea was determined by the live fruit pricking method (Wang, K., Liao, Y., Kan, J., Han, L., Zheng, Y. Response of direct or priming defense against Botrytis cinerea to methyljasmonate treatment at different concentrations in grape berries. Int. J. Food Microbiol. 2015, 194, 32-39.). The specific operation method of the live fruit pricking method is referenced to the literature. Select healthy Sunshine Rose grapes of similar size, clean the surface of the fruit with clean water, immerse in a disinfectant solution containing 75% ethanol for 1 min, and dry. Dissolve the compound in DMSO to prepare a mother solution, and prepare the test solution with sterile water containing 0.3% Tween 80 (the compound concentration is 50μg / mL and 100μg / mL, and the control agent is boscalid at 100μg / mL). Set a control CK with inoculation without drug application and equal amount of solvent. Use the fruit soaking method, soak for 5-10 seconds, and dry. Then rinse the surface of the PDA plate where the gray mold fungus has been cultured for 10-14 days with sterile water to obtain a spore suspension. Use a gun to make a 2mm wide wound on the central surface of the clean grape fruit and suck out the overflowing juice. Take 10μL of the gray mold fungus spore suspension (10 5 / mL), injected into the wound of grape fruit, then placed the inoculated grapes in a fresh-keeping box, placed in a greenhouse at 23-26℃, 60%-80% dark for 6 days, observed and photographed every day until the inoculated control without drug application became obviously ill, measured the diameter of the fruit lesions on the 2nd, 4th and 6th day after drug application, measured the diameter of the lesions on all treated grape fruits, and calculated the in vivo control effect of the compound according to the following formula. Each treatment group includes 3 replicates, and each replicate uses 10 grapes.

[0113] Fruit lesion diameter = average of the vertical and horizontal diameters of the fruit lesion;

[0114] Control effect (%) = 100 × (control lesion diameter - treatment lesion diameter) / control lesion diameter

[0115] Test results: The results of the in vivo tissue test are shown in Table 2. Compound Z14 has a high control effect on tomato gray mold, and the effect increases with the extension of the treatment time. The control effect is 65.03% at a test concentration of 100 μg / mL on the 6th day after treatment, which is not significantly different from the control agent boscalid. In summary, isoquinoline-3-acylhydrazone cycloalkane compounds have potential antibacterial activity against tomato gray mold, and have a novel structure and a simple synthesis method. They are expected to be further studied and developed into a new type of fungicide candidate compound.

[0116] Table 2 The efficacy of the compounds prepared in Example Z14 against tomato gray mold

[0117]

[0118] Note: Different letters in the table indicate significant differences at the P 0.05 level.

[0119] Experimental summary: The fungicidal activity of the isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds prepared in Examples 3-12 of the present invention against tomato gray mold, rice sheath blight, wheat fusarium, mango anthracnose, pepper phytophthora and citrus acid rot was tested. The results showed that the fungicidal activity of compounds Z1-Z10 containing acylhydrazone biphenyl groups was low, the fungicidal activity trend of phenylhydrazone compounds Z17-Z25 was similar to that of acylhydrazone biphenyl compounds, and acylhydrazone cycloalkane compounds Z13-Z16 had high fungicidal activity, especially against tomato gray mold and mango anthracnose, which was better than the control agent boscalid. The in vivo tissue test of the isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compound prepared in Example Z14 of the present invention shows that the compound Z14 has a high control effect on tomato gray mold, and the effect increases with the extension of the treatment time. The control effect is 65.03% at a test concentration of 100 μg / mL on the 6th day after treatment, which is not significantly different from the control agent boscalid. Therefore, the isoquinoline-3-acylhydrazone cycloalkane compound has a novel structure, a simple synthesis method, and potential antibacterial activity against tomato gray mold, and is expected to be further studied and developed into a new type of fungicide candidate compound.

[0120] The above description is merely an exemplary 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. An isoquinoline-3-acylhydrazone aromatic ring cycloalkane compound, characterized in that: Its general structural formula is shown in Formula 1, Formula 2 or Formula 3: In the formula, R1 is a hydrogen atom, a hydroxyl group, a fluorine atom, a chlorine atom, a bromine atom, a trifluoromethyl group, an amino group, a mercapto group, a C 1-12 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylamino, C 1-6 One of the alkylthio groups.

2. The isoquinoline-3-acylhydrazone aromatic ring cycloalkane compound according to claim 1, characterized in that: In Formula 1, R2 is C 3-10 Cycloalkyl, halogen-substituted C 3-10 Cycloalkyl, C 1-4 Hydrocarbon-substituted C 3-10 Cycloalkyl, C 1-4 Hydroxyl substituted C 3-10 A cycloalkyl group.

3. The isoquinoline-3-acylhydrazone aromatic ring cycloalkane compound according to claim 1, characterized in that: In Formula 1, R2 is one of cyclopropane, cyclobutane, cyclopentane, cyclohexane and cycloheptane.

4. The isoquinoline-3-acylhydrazone aromatic ring cycloalkane compound according to claim 1, characterized in that: In Formula 2 and Formula 3, R2 and R3 are C 1-4 Hydrocarbon-substituted phenyl, C 1-4 phenyl substituted with alkoxy, benzyl substituted with halogen, phenyl substituted with nitro, phenyl substituted with cyano, phenyl substituted with ester, pyridyl substituted with halogen, C 1-4 Hydrocarbyl-substituted pyridyl, C 1-4 A type of pyridyl substituted with an alkoxy group.

5. The isoquinoline-3-acylhydrazone aromatic ring cycloalkane compound according to any one of claims 1 to 4 is used for preventing and controlling plant fungal diseases caused by fungal pathogens in agriculture.

6. The use according to claim 5, characterized in that The fungal pathogens include tomato gray mold, rice blast, rice false smut, rice sheath blight, wheat fusarium rust, wheat stripe rust, wheat powdery mildew, soybean root rot, mango anthracnose, rubber anthracnose, banana anthracnose, cucumber polysporus, apple rot, and melon vine blight.

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