Isoquinoline-3-acyl hydrazone aromatic ring cycloalkane compounds and their application in plant disease control

Abstract

The application provides isochinoline-3-acyl hydrazone aromatic ring cycloalkane compounds and application thereof in plant disease prevention, and the structural general formula is as shown in formula 1, formula 2 and formula 3: R1 is one of hydrogen atom, hydroxyl, fluorine atom, chlorine atom, bromine atom, trifluoromethyl, amino, sulfydryl, C 1‑12 alkyl, C 1‑6 alkoxy, C 1‑6 alkylamino, C 1‑6 alkylthiol. The isochinoline-3-acyl hydrazone aromatic ring cycloalkane compounds are applied to prevention and treatment of plant fungal diseases caused by fungal pathogens in agriculture. The raw materials of the isochinoline-3-acyl hydrazone aromatic ring / cycloalkane compounds are easy to obtain, the synthesis method is simple and practical, the cost is low, the isochinoline-3-acyl hydrazone aromatic ring / cycloalkane compounds have excellent inhibition effect on plant fungal diseases, and the structure is novel. The research result has a positive significance for the creation of new pesticides.

Description

Technical Field

[0001] This invention relates to the field of pesticide technology, specifically to isoquinoline-3-acylhydrazone aromatic cycloane compounds and their application in the control of plant diseases. Background Technology

[0002] Fungal diseases of plants have always been a major challenge in agricultural production, such as rice blast, sheath blight, wheat scab, stripe rust, cotton verticillium wilt, and rapeseed sclerotinia stem rot, severely impacting crop yield and quality. Chemical control is an important means of pest control; however, current pesticides, such as triazoles, methoxyacrylates, and succinate dehydrogenase inhibitors, have led to severe resistance due to long-term and excessive use, threatening agricultural product safety and posing environmental risks. Therefore, there is an urgent need to develop novel, highly effective, low-toxicity, and environmentally friendly fungicides to control these increasingly serious plant diseases.

[0003] Isoquinoline-3-carboxylic acid is an isoquinoline compound. The research team discovered for the first time that this compound has broad-spectrum bactericidal activity against plant pathogenic bacteria. Based on this, 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, they modified the structure of this compound and found that isoquinoline compounds containing acylhydrazone disulfone groups have strong bactericidal activity against plant pathogenic bacteria (isoquinoline-3-acylhydrazone disulfone compounds and their preparation methods and applications, application number: 202311550250.8). However, this type of structure has poor bactericidal effect against plant pathogenic fungi. In order to create isoquinoline compounds with novel structures and higher bactericidal activity, the research team used isoquinoline-3-carboxylic acid as the lead skeleton and adopted the pharmacophore active splicing technology to introduce an acylhydrazone aromatic ring and an acylhydrazone cycloalkyl group into the 3-carboxyl group of its active site. They designed and synthesized a new type of isoquinoline compound containing an acylhydrazone aromatic ring / cycloalkyl group, which has excellent bactericidal activity against a variety of plant pathogenic fungi such as tomato gray mold. Summary of the Invention

[0004] Based on the existing technology, the technical problem to be solved by the present invention is isoquinoline-3-acylhydrazone aromatic cycloalkane compounds and their application in the prevention and control of plant diseases, so as to solve the above-mentioned problem.

[0005] The technical solution of this invention:

[0006] Isoquinoline-3-acylhydrazone aromatic cycloalkyl compounds, characterized in that their general structural formula is shown in Formula 1, Formula 2 or Formula 3:

[0007]

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

[0009] Furthermore, in Equation 1, R2 is C 3-10 Cycloalkyl, halogen-substituted C 3-10 cycloalkyl, C 1-4 C with hydrocarbon substitution 3-10 cycloalkyl, C 1-4 alkyloxy-substituted C 3-10 One of the cycloalkyl groups.

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

[0011] Furthermore, in equations 2 and 3, R2 and R3 are C 1-4 Hydrocarbon-substituted phenyl, C 1-4 alkyloxylated phenyl, halogen-substituted benzyl, nitro-substituted phenyl, cyano-substituted phenyl, ester-substituted phenyl, halogen-substituted pyridyl, C 1-4 Hydrocarbon-substituted pyridyl, C 1-4 One of the pyridinyl groups substituted with alkyloxy groups.

[0012] Compared with the prior art, the beneficial effects of the present invention are:

[0013] (1) The acylhydrazone compounds of the present invention have high bactericidal activity, especially against tomato gray mold and mango anthracnose, and the activity increases with the extension of treatment time. On the 6th day after treatment, the control efficacy was 65.03% at the test concentration of 100 μg / mL.

[0014] (2) The acylhydrazone compounds of the present invention have high bactericidal activity against mango anthracnose, with an inhibition rate of 60.46%-71.79%, which is better than the control agent cytotoxicant.

[0015] (3) The isoquinoline-3-acylhydrazone compounds of the present invention have novel structures, readily available raw materials, simple and practical synthesis methods, low cost, and excellent inhibitory effects on plant fungal diseases. Attached Figure Description

[0016] Figure 1 Z14 proton spectrum

[0017] In the figure, the horizontal axis f1 refers to the chemical shift, which represents the position of the spectral peak. Detailed Implementation

[0018] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention. Unless otherwise specified, the experimental methods used in the embodiments of this invention are conventional methods.

[0019] Unless otherwise specified, all materials and reagents used in the embodiments of this invention can be obtained commercially.

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

[0021] Example 1

[0022] compound The preparation of [the compound] was carried out, and it was named compound 1.

[0023]

[0024] 4-Cyanophenylacetic acid (2.0 mmol) was added to a round-bottom flask to replace the system with an inert environment. 10 mL of dry DMF (dimethylformamide) was added, and the system was placed in a -30°C low-temperature bath. A solution of bis(trimethylsilylamino) lithium (8.0 mmol) and THF (tetrahydrofuran) was slowly added dropwise. Ten minutes after the addition was complete, methyl 3-trifluoromethylbenzoate (2.02 mmol) was added dropwise. The system temperature was maintained at -30°C for 2 hours, then slowly raised to room temperature for 8 hours. After TLC (thin-layer chromatography) monitoring, the reaction was quenched by slowly adding saturated ammonium chloride solution. The mixture was extracted with ethyl acetate, washed twice with water, and the organic phase was dried before solvent removal to obtain the crude product. The crude product was purified by column chromatography (eluent: petroleum ether:ethyl acetate = 10:1 (V:V), Rf = 0.56) to give a pale yellow solid compound 1, with a yield of 87.8%.

[0025]

[0026] Isoquinoline-3-hydrazide (2.0 mmol) was added to a reaction tube, followed by 11 mL of a methanol:n-hexane 10:1 mixture. After stirring until homogeneous, compound 1 (2.0 mmol) was added, and 3–5 drops of trifluoroacetic acid were added dropwise. The reaction was heated to reflux and carried out for 6 hours, monitored by TLC. After the reaction was complete, the solvent was removed, and the mixture was recrystallized from methanol or purified by column chromatography (eluent: petroleum ether:ethyl acetate = 2:1 (V:V)) to give 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 The preparation of it was named Z2.

[0030] Compound Z2 was prepared using the same method as compound Z1; it is a pale 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 The preparation of it was named Z3.

[0033] Compound Z3 was prepared using the same method as compound Z1; it is a 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 The preparation of it was named Z4.

[0036] Compound Z4 was prepared using the same method as compound Z1; it is a 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 The preparation of it was named Z5.

[0039] Compound Z5 was prepared using the same method as compound Z1; it is a 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 The preparation of it was named Z6.

[0042] Compound Z6 was prepared using the same method as compound Z1; it is a 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 The preparation of it was named Z7.

[0045] Compound Z7 was prepared using the same method as compound Z1; it is an 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 The preparation of it was named Z8.

[0048] Compound Z8 was prepared using the same method as compound Z1; it is a 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 The preparation of it was named Z9.

[0051] Compound Z9 was prepared using the same method as compound Z1; it is a pale 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 The preparation of this material was named Z10.

[0054] Compound Z10 was prepared using the same method as compound Z1; it is a 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] Example 11

[0056] compound The preparation of it was named Z11.

[0057] Compound Z11 was prepared using the same method as compound Z1; it is a pale 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 The preparation of it was named Z12.

[0060] Compound Z12 was prepared using the same method as compound Z1; it is a pale 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 The preparation of it was named Z13.

[0063]

[0064] Isoquinoline-3-hydrazide (2.0 mmol) was added to a reaction tube, followed by 11 mL of a methanol:n-hexane 10:1 mixture. After stirring until homogeneous, cycloheptanone (2.0 mmol) was added, and 3–5 drops of trifluoroacetic acid were added dropwise. The reaction was heated to reflux and carried out for 6 hours, with TLC monitoring. After the reaction was complete, the solvent was removed, and the mixture was recrystallized from methanol or purified by column chromatography (eluent: petroleum ether:ethyl acetate = 2:1 (V:V)) to give a white solid compound, which was 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] Example 14

[0067] compound The preparation of the compound was named compound Z14.

[0068] Compound Z14 was prepared using the same method as compound Z13. It is a white solid. ¹H NMR (400 MHz, Chloroform-d) δ 10.95 (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] Example 15

[0070] compound The preparation of it was named Z15.

[0071] Compound Z15 was prepared using the same method as compound Z13; it is a 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 The preparation of this was named Z16.

[0074] Compound Z16 was prepared using the same method as compound Z13; it is a 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] Example 17

[0076] compound The preparation of this material was named Z17.

[0077] Compound Z17 was prepared using the same method as compound Z13; it is a 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] Example 18

[0079] compound The preparation of it was named Z18.

[0080] Compound Z18 was prepared using the same method as compound Z13; it is a 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] Example 19

[0082] compound The preparation of this was named Z19.

[0083] Compound Z19 was prepared using the same method as compound Z13; it is a 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] Example 20

[0085] compound The preparation of this was named Z20.

[0086] Compound Z20 was prepared using the same method as compound Z13; it is a 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] Example 21

[0088] compound The preparation of it was named Z21.

[0089] Compound Z21 was prepared using the same method as compound Z13; it is a 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] Example 22

[0091] compound The preparation of it was named Z22.

[0092] Compound Z22 was prepared using the same method as compound Z13; it is a 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] Example 23

[0094] compound The preparation of it was named Z23.

[0095] Compound Z23 was prepared using the same method as compound Z13; it is a 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] Example 24

[0097] compound The preparation of it was named Z24.

[0098] Compound Z24 was prepared using the same method as compound Z13; it is a 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] Example 25

[0100] compound The preparation of it was named Z25.

[0101] Compound Z25 was prepared using the same method as compound Z13; it is a 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 the fungicidal activity of isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds against plant pathogenic fungi

[0103] The tested plant pathogenic bacteria were: *Botrytis cinerea* (tomato gray mold), *Colletotrichum gloeosporioides* (mango anthracnose causal agent), *Rhizoctonia solani* (rice sheath blight), *Fusarium graminearum* (wheat scab), *Phytophthora capsici* (pepper causal agent), and *Lasiodiplodia pseudotheobromae* (green orange fruit rot causal agent). The tested plant pathogenic bacteria were preserved at the Institute of Environment and Plant Protection, Chinese Academy of Tropical Agricultural Sciences – Green Pesticide Creation and Application Research Group.

[0104] Fungicidal activity test method: The fungicidal activity of the compounds prepared in Examples 3-12 against plant pathogenic fungi was tested (see Table 1). This invention uses the growth rate method to evaluate the fungicidal activity of isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds against six plant fungi, including *Botrytis cinerea*, the causal agent of tomato rot. The experimental method follows the method described by Fang Zhongda (Fang Zhongda. Plant Disease Research Methods. Beijing: China Agriculture Press, 1998). Mycelial growth was carefully observed and recorded under an inverted microscope (400X). The inhibitory effect of isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds on mycelial growth of plant pathogenic fungi was determined using a screening concentration of 100 μg / mL. Pathogens showing high inhibitory activity were subjected to tissue assays to verify their activity intensity. Each treatment was repeated three times (three petri dishes), with a blank culture medium as a control.

[0105] Mycelial growth inhibition rate (%) = (Control colony diameter - Treated colony diameter - Control colony diameter) / Control colony diameter × 100%

[0106] Experimental Results: The fungicidal activities of 25 isoquinoline-3-acylhydrazone aromatic ring / cycloalkanes against *Botrytis cinerea* (tomato causal agent), *Rhizoctonia solani* (rice sheath blight), *Fusarium graminearum* (wheat scab), *Anthracnose* (mango anthracnose), *Phytophthora capsici* (pepper causal agent), and *Acid rot* (citrus sour rot) were tested. The results showed that compounds Z1-Z10 containing acylhydrazone biphenyl groups generally exhibited low fungicidal activity, with inhibition rates ranging from 25% to 50% at a tested concentration of 100 μg / mL. The fungicidal activity trends of phenylhydrazone compounds Z17-Z25 were similar to those of acylhydrazone biphenyl compounds. Similar compounds; acylhydrazone compounds Z13-Z16 exhibit high fungicidal activity, especially against tomato gray mold, with inhibition rates of 87.68%, 90.50%, 85.14%, and 86.43% at the tested concentration of 100 μg / mL, respectively. Simultaneously, these compounds also show high fungicidal activity against mango anthracnose, with inhibition rates of 60.46%, 71.79%, 57.86%, and 62.86%, respectively, superior to the control agent, cyazofamid.

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

[0108]

[0109]

[0110] Experiment 2: Histological determination of compound Z-14 against tomato gray mold.

[0111] Test material: Grapes, the grape variety being commercially available Sunshine Rose.

[0112] Pot experiment method: The in vivo effect of the compound on Botrytis cinerea to methyljasmonate treatment at different concentrations in grape berries was determined by the live fruit needle prick 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.). Specific procedures for the live fruit needle prick method are detailed in the literature. Healthy Shine Muscat grapes of similar size were selected, the fruit surface was cleaned with water, and the fruits were immersed in a disinfectant solution containing 75% ethanol for 1 minute, then air-dried. The compound was dissolved in DMSO to prepare a stock solution, and the test solutions (compound concentrations of 50 μg / mL and 100 μg / mL, with 100 μg / mL of cymoxanil as the control agent) were prepared using sterile water containing 0.3% Tween 80. A control (CK) was established, inoculated without treatment but with an equal amount of solvent. The spore suspension was obtained by immersion in the sap for 5-10 seconds, followed by air drying. Then, the surface of the PDA plate containing *Botrytis cinerea* cultured for 10-14 days was rinsed with sterile water. A 2mm wide wound was made in the center of a clean grape berry using a pipette tip, and the overflowing juice was aspirated. 10 μL of the *Botrytis cinerea* spore suspension (10...) 5 Inject the compound (infected grapes per mL) into the wounds on the grape berries. Then, place the inoculated grapes in a sealed container and incubate in the dark at 23-26℃ and 60%-80% humidity for 6 days. Observe and photograph the grapes daily until the control group (inoculated but not treated) shows obvious signs of disease. Measure the diameter of lesions on the fruit on days 2, 4, and 6 after treatment. Measure the diameter of lesions on the grape berries of all treatments and calculate the in vivo control effect of the compound using the formula below. Each treatment group includes 3 replicates, with 10 grapes used per replicate.

[0113] Fruit lesion diameter = average of the longitudinal and transverse diameters of the fruit lesion;

[0114] Control efficacy (%) = 100 × (diameter of control lesions - diameter of treated lesions) / diameter of control lesions

[0115] Experimental Results: Table 2 shows the results of the in vivo tissue method test. Compound Z14 exhibits high control efficacy against tomato gray mold, and this efficacy increases with treatment time. On day 6 after treatment, at a tested concentration of 100 μg / mL, the control efficacy was 65.03%, which was not significantly different from the control agent, boscalid. In summary, isoquinoline-3-acylhydrazone compounds possess potential antifungal activity against tomato gray mold, and their novel structure and simple synthesis method suggest their potential for further research and development into a new class of fungicide candidates.

[0116] Table 2 shows the control efficacy of the compound 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 activities of the isoquinoline-3-acylhydrazone aromatic ring / cycloalkane compounds prepared in Examples 3-12 of this invention against *Botrytis cinerea* (tomato causal agent), *Rhizoctonia solani* (rice sheath blight), *Fusarium graminearum* (wheat scab), *Anthracnose* (mango anthracnose), *Phytophthora capsulatum* (pepper causal agent), and *Acid rot* (citrus rot) were tested. The results showed that compounds Z1-Z10 containing acylhydrazone biphenyl groups had low fungicidal activity, while the fungicidal activity trend of phenylhydrazone compounds Z17-Z25 was similar to that of acylhydrazone biphenyl compounds. Acylhydrazone cycloalkane compounds Z13-Z16 had high fungicidal activity, especially against *Botrytis cinerea* (tomato causal agent) and *Anthracnose* (mango anthracnose), and were superior to the control agent cyazofamid. In vivo tissue assays of the isoquinoline-3-acylhydrazone aromatic / cycloalkane compound prepared in Example Z14 of this invention showed that compound Z14 exhibited high control efficacy against tomato gray mold, with the efficacy increasing with treatment time. On day 6 after treatment, at a tested concentration of 100 μg / mL, the control efficacy was 65.03%, showing no significant difference compared to the control agent, boscalid. Therefore, isoquinoline-3-acylhydrazone cycloalkane compounds possess novel structures, simple synthesis methods, and potential antifungal activity against tomato gray mold, and are expected to be further studied and developed into a novel class of fungicide candidates.

[0120] The above description is merely an example of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. An isoquinoline-3-acylhydrazone aromatic cycloalkyl compound, characterized in that, Its general structural formula is shown in Equation 1 or Equation 3: ； In the formula, R1 represents a hydrogen atom, hydroxyl group, fluorine atom, chlorine atom, bromine atom, trifluoromethyl group, amino group, mercapto group, or C. 1-12 Alkyl, C 1-6 Alkoxy, C 1-6 Alkylamino, C 1-6 One of the alkyl mercapto groups; In Equation 1, R2 is C 3-10 Cycloalkyl, halogen-substituted C 3-10 cycloalkyl, C 1-4 C with hydrocarbon substitution 3-10 cycloalkyl, C 1-4 alkyloxylated C 3-10 One of the cycloalkyl groups; In Equation 3, R2 and R3 are C 1-4 Hydrocarbon-substituted phenyl, C 1-4 alkyloxylated phenyl groups, halogenated benzyl groups, nitro-substituted phenyl groups, cyano-substituted phenyl groups, C 1-4 Hydrocarbon-substituted pyridyl, C 1-4 One of the pyridinyl groups substituted with alkyloxy groups.

2. The isoquinoline-3-acylhydrazone aromatic cycloalkyl compound as described in claim 1, characterized in that, In Formula 1, R2 is one of cyclopropane, cyclobutane, cyclopentane, cyclohexane, and cycloheptane.

3. The isoquinoline-3-acylhydrazone aromatic cycloalkyl compounds as described in claim 1 or 2 are used to control plant fungal diseases caused by fungal pathogens in agriculture.

4. The application as described in claim 3, characterized in that, The fungal pathogens include tomato gray mold, rice blast fungus, rice false smut fungus, rice sheath blight fungus, wheat scab fungus, wheat stripe rust fungus, wheat powdery mildew fungus, soybean root rot fungus, mango anthracnose fungus, rubber anthracnose fungus, banana anthracnose fungus, cucumber polyphylla, apple rot fungus, and melon vine blight fungus.

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