A 4-aminopyrimidinehydrazone compound containing a diphenyl ether group, and its preparation method and application

Abstract

The present invention relates to a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group, a preparation method, and an application thereof. The compound is a compound represented by Formula I, or a stereoisomer, geometric isomer, tautomer, racemate, nitrogen oxide, hydrate, solvate, or pharmaceutically acceptable salt of the compound represented by Formula I. The 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to the present invention has good activity in inhibiting the growth of plant pathogenic fungi.

Description

Technical Field

[0001] The invention belongs to the technical field of pesticides, and particularly relates to a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group, a preparation method and an application thereof. Background Art

[0002] Chemical control is currently one of the most effective means of plant disease prevention and management. However, the frequent use and abuse of chemical fungicides has accelerated the emergence and development of fungal resistance, posing a huge challenge to agriculture. Therefore, it is urgent to develop new types of fungicides to meet the needs of agricultural production.

[0003] Thiamine pyrophosphate (ThDP) is a coenzyme for many important enzymes in the metabolic processes of organisms, such as pyruvate dehydrogenase E1 and acetolactate synthase. Therefore, the rational design of pesticide molecules using ThDP as a guide has high research value. Currently, multiple structural types of ThDP analogues have been reported, such as compounds I-VII. However, these compounds have complex structures and are difficult to synthesize. In addition, these thiamine pyrophosphate analogues have not yet shown any application value in agriculture.

[0004]

[0005] Hydrazone compounds are a class of Schiff base compounds formed by the condensation of hydrazine and a carbonyl group. Many of these compounds exhibit certain biological activity, and some such pesticides have been commercialized, such as the fungicide Benquiox, Ferimzone, the intestinal fungicide Nifuroxazide, and Compound A, which have excellent inhibitory activity against Rhizoctonia solani. Previous research by the inventor's research group has found that a class of hydrazone compounds shown in the following formula has pyruvate dehydrogenase E1 inhibitory activity. However, the inhibitory activity of these hydrazone compounds against pathogens is generally low, especially against dollar spot pathogen and Sclerotinia sclerotiorum.

[0006] Summary of the Invention

[0007] The technical problem solved by the present invention is to provide a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group, a preparation method and application thereof, and the compound has good activity in inhibiting the growth of plant pathogenic fungi.

[0008] The specific solution provided by the present invention includes the following steps:

[0009] In a first aspect of the present invention, a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group is provided, wherein the compound is a compound represented by Formula I or a stereoisomer, geometric isomer, tautomer, racemate, nitrogen oxide, hydrate, solvate, or pharmaceutically acceptable salt of the compound represented by Formula I:

[0010]

[0011] Among them, R 1 is hydrogen or methyl;

[0012] R 2 It is a monosubstituted or polysubstituted group on the benzene ring.

[0013] Preferably, R 2 When it is a multi-substituted group, each group in the multi-substituted group is independently selected from halogen, C 1-10 Alkyl, -CF3 or alkoxy, any two substituents in each group are located at the para position, meta position or ortho position, and the R 2 When it is a monosubstituted group, the R 2 Selected from halogen, -CF3, C 1-10 alkyl or alkoxy;

[0014] Optionally, the halogen is fluorine, chlorine, bromine or iodine;

[0015] Optionally, the R 2 Selected from C 1-4 alkyl;

[0016] Optionally, the alkoxy group is C 1-6 Alkoxy.

[0017] Optionally, the compound is the following compound or a stereoisomer, geometric isomer, tautomer, racemate, nitrogen oxide, hydrate, solvate, or pharmaceutically acceptable salt thereof:

[0018]

[0019]

[0020] The inventors found through experiments that compounds 1-24 exhibited excellent fungicidal activity.

[0021] In a second aspect of the present invention, a method for preparing the above-mentioned 4-aminopyrimidinehydrazone compound containing a diphenyl ether group is provided, wherein the compound represented by Formula II and the compound represented by Formula III are dissolved in a first organic solvent in the presence of an acid catalyst, and heated at 60 to 90 degrees Celsius to react to obtain the compound represented by Formula I.

[0022]

[0023] Optionally, the first organic solvent is at least one selected from acetonitrile, ethanol, 1,2-dichloroethane, acetone, tert-butanol, toluene, benzene, xylene, ethyl acetate, methanol, n-hexane, dichloromethane, chloroform, tetrahydrofuran, dimethyl sulfoxide and N,N-dimethylformamide.

[0024] Optionally, the acid catalyst is selected from at least one of ascorbic acid, acetic acid, tartaric acid, trifluoroacetic acid, formic acid, salicylic acid, and malic acid. When the acid catalyst is used, the reaction efficiency can be improved.

[0025] Preferably, the molar ratio of the compound represented by Formula II to the compound represented by Formula III and the acid catalyst is 1:(1-1.5):(0.01-0.15). Under these conditions, the compound represented by Formula II can be reacted completely, and post-processing is simple, thereby obtaining the target compound with a higher yield.

[0026] Preferably, the temperature of the heating reaction is 64-78 degrees Celsius; thereby, the reaction rate can be increased and the target compound can be obtained with a higher yield. If the reaction temperature is too low, the reaction will not occur or will react very slowly, resulting in reaction failure or a very low yield. The optimal reaction temperature is between 64-78 degrees Celsius. If the reaction temperature is too high, the reaction cost will be increased.

[0027] Optionally, the heating reaction time is 2 to 60 hours.

[0028] Preferably, the heating reaction time is 3 to 48 hours. This ensures that the reactants react fully and the target compound is obtained in a high yield. If the reaction time is too short, the reaction is incomplete, which not only reduces the yield but also increases the difficulty of post-processing. If the reaction time is too long, exceeding the optimal time, the yield is not significantly affected. At a similar yield, it not only increases costs but also wastes time.

[0029] In a third aspect, the present invention provides a pesticide comprising a compound of Formula I or a stereoisomer, geometric isomer, tautomer, racemate, nitrogen oxide, hydrate, solvate, or pharmaceutically acceptable salt of the compound of Formula I. The present invention has discovered that the compound of Formula I can be effectively used to inhibit the growth of plant pathogenic fungi.

[0030] In a fourth aspect, the present invention provides a method for preventing or treating plant diseases, comprising applying the compound or pesticide as described above to the plant.

[0031] Optionally, the plant disease is caused by at least one of peach brown rot, apple ring rot, pepper phytophthora, fusarium spp., fusarium head blight, pythium spp., rapeseed sclerotinia, and dollar spot.

[0032] Preferably, the plant disease is caused by one of Psoralea corylifolia or Sclerotinia sclerotiorum.

[0033] Optionally, the plant is apple, peach or rapeseed.

[0034] The technical solution of the present invention has the following beneficial effects:

[0035] (1) The 4-aminopyrimidinehydrazone compounds containing diphenyl ether groups of the present invention have not been reported. The inventors of the present application used thiamine pyrophosphate (ThDP), a common coenzyme of important enzymes in multiple metabolic processes in organisms, as a guide to design and actually synthesize its analogs. In particular, they explored and discovered new structural ThDP analogs with application value in agricultural fungi, which have important research significance and application value for the development of new and efficient fungicides.

[0036] (2) The compounds of the present invention have good activity in inhibiting the growth of plant pathogenic fungi, especially against Sclerotinia sclerotiorum and Pseudomonas aeruginosa. On the one hand, after the 4-aminopyrimidinehydrazone compound is introduced with a diphenyl ether structural unit having a flexible structure, the target compound synthesized by connecting it can easily adjust its conformation in the enzyme active cavity, thereby obtaining an optimal binding mode and improving the fungicidal activity of the substance. On the other hand, the diphenyl ether structural unit is a highly lipophilic fragment, which helps the molecule penetrate the cell membrane and improves the solubility of the molecule, thereby improving the fungicidal activity.

[0037] (3) The preparation method of 4-aminopyrimidinehydrazone compounds containing diphenyl ether groups proposed in the present invention has cheap and easily available raw materials, adopts a one-pot process, has mild reaction conditions, high synthesis efficiency, high product purity, high yield, low production cost, and is conducive to large-scale preparation; the preparation process is simple and easy to control, does not involve special reaction equipment, meets the requirements of safe production and green chemistry, and is suitable for large-scale industrial production.

[0038] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. DETAILED DESCRIPTION

[0039] The following will further describe in detail the general formula compounds of the present invention, their preparation methods, and applications with reference to specific examples. The following examples are intended only to illustrate and explain the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are encompassed within the scope of protection intended by the present invention.

[0040] Unless otherwise stated, the raw materials and reagents used in the examples are commercially available.

[0041] Example 1

[0042]

[0043] The preparation method of compound 1 comprises the following steps: dissolving 2 mmol of 2-methyl-4-amino-5-formaldehyde pyrimidine and 2 mmol of 4-phenoxyphenylhydrazine in 15 mL of anhydrous ethanol, adding 0.02 mmol of glacial acetic acid, heating under reflux with stirring for 7 hours, and monitoring the reaction progress by TLC. After the reaction is completed, 20 ml of water is added, and a solid is precipitated by stirring. The solid is filtered and dried to obtain a yellow solid with a yield of 60% and an mp of 202-204°C.

[0044] 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.39 (s, 1H, NH), 8.20 (s, 1H, pyrimidine-H), 7.94 (s, 1H, CH=N), 7.77 (s, 2H, NH2), 7.3 3(t,J=7.9Hz,2H,Ar-H),7.05(d,J=7.3Hz,1H,Ar-H),6.99(m,4H,Ar-H),6.92(d,J=7.9Hz,2H,Ar-H),2.38(s,3H,CH3);

[0045] HRMS(ESI):calcd.for C 18 H 18 N5O[M+H] + 320.1506,found:320.1511.

[0046] Example 2

[0047]

[0048] The preparation method of compound 2 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 4-(4-chloro-phenoxy)phenylhydrazine.

[0049] Product structure identification data: 1H NMR (400MHz, DMSO-d6) δ (ppm): 10.42 (s, 1H, NH), 8.21 (s, 1H, pyrimidine-H), 7.95 (s, 1H, CH=N), 7.76 (s ,2H,NH2),7.39(d,J=8.9Hz,2H,Ar-H),7.01(m,4H,Ar-H),6.94(d,J=8.9Hz,2H,Ar-H),2.39(s,3H,CH3);

[0050] HRMS(ESI):calcd.for C 18 H 17 ClN5O[M+H] + 354.1116,found:354.1122.

[0051] Example 3

[0052]

[0053] The preparation method of compound 3 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 4-(4-bromo-phenoxy)phenylhydrazine.

[0054] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.41 (s, 1H, NH), 8.20 (s, 1H, pyrimidine-H), 7.94 (s, 1H, CH=N), 7.77 (s, 2H ,NH2),7.49(d,J=8.9Hz,2H,Ar-H),7.05-6.96(m,4H,Ar-H),6.88(d,J=8.9Hz,2H,Ar-H),2.38(s,3H,CH3);

[0055] HRMS(ESI):calcd.for C 18 H 17 BrN5O[M+H] + 398.0611,found:398.0608.

[0056] Example 4

[0057]

[0058] The preparation method of compound 4 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 4-(4-methylphenoxy)phenylhydrazine.

[0059] Product structure identification data: 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.38 (s, 1H, NH), 8.22 (s, 1H, pyrimidine-H), 7.95 (s, 1H, CH=N), 7.80 (s, 2H, NH2), 7.16 (d, J=8.5 Hz, 2H, Ar-H), 6.98 (m, 4H, Ar-H), 6.84 (d, J=8.5 Hz, 2H, Ar-H), 2.40 (s, 3H, CH3), 2.28 (s, 3H, CH3);

[0060] HRMS(ESI):calcd.for C 19 H 20 N5O[M+H] + 334.1662,found:334.1664.

[0061] Example 5

[0062]

[0063] The preparation method of compound 5 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 4-(2,4-dichloro-phenoxy)phenylhydrazine.

[0064] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.44 (s, 1H, NH), 8.22 (s, 1H, pyrimidine-H), 7.96 (s, 1H, CH=N), 7.77 (s, 2H, NH2), 7.74 (d,J=2.4Hz,1H,Ar-H),7.41-7.33(m,1H,Ar-H),7.06-6.97(m,4H,Ar-H),6.90(d,J=8.8Hz,1H,Ar-H),2.39(s,3H,CH3);

[0065] HRMS(ESI):calcd.for C 18 H 16 Cl2N5O[M+H] + 388.0726,found:388.0740.

[0066] Example 6

[0067]

[0068] The preparation method of compound 6 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 4-(2-chloro-4-trifluoromethylphenoxy)phenylhydrazine.

[0069] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.46 (s, 1H, NH), 8.21 (s, 1H, pyrimidine-H), 8.00-7.92 (m, 2H, Ar-H), 7.74 (s, 2H, NH2), 7.64 (dd ,J=8.7,1.6Hz,1H,CH=N),7.10(d,J=8.9Hz,2H,Ar-H),7.02(d,J=8.9Hz,2H,Ar-H),6.95(d,J=8.7Hz,1H,Ar-H),2.38(s,3H,CH3);

[0070] HRMS(ESI):calcd.for C 19 H 16 ClF3N5O[M+H] + 422.0990,found:422.0992.

[0071] Example 7

[0072]

[0073] The preparation method of compound 7 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 2-phenoxyphenylhydrazine.

[0074] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.02 (s, 1H, NH), 8.21 (s, 1H, pyrimidine-H), 8.10 (s, 1H, CH=N), 7.79 (s, 2H, NH2), 7.37 (t, J=7.8Hz, 2H, Ar -H),7.26(d,J=8.0Hz,1H,Ar-H),7.17-7.06(m,2H,Ar-H),6.99(d,J=8.0Hz,2H,Ar-H),6.89-6.74(t,J=7.8Hz,2H,Ar-H),2.37(s,3H,CH3);

[0075] HRMS(ESI):calcd.for C 18 H 16 N5O[M+H] + 320.1506,found:320.1505.

[0076] Example 8

[0077]

[0078] Product structure identification data: The preparation method of compound 8 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 2-(4-chloro-phenoxy)phenylhydrazine.

[0079] 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.02 (s, 1H, NH), 8.19 (s, 1H, pyrimidine-H), 8.10 (s, 1H, CH=N), 7.78 (s, 2H, NH2), 7.41 (d, J=8.9Hz, 2H, Ar-H), 7.27 (d, J=7.9Hz,1H,Ar-H),7.17(t,J=7.5Hz,1H,Ar-H),6.98(d,J=8.9Hz,2H,Ar-H) ,6.91(d,J=7.8Hz,1H,Ar-H),6.81(t,J=7.6Hz,1H,Ar-H),2.37(s,3H,CH3);

[0080] HRMS(ESI):calcd.for C 18 H 17 ClN5O[M+H] + 354.1116,found:354.1121.

[0081] Example 9

[0082]

[0083] The preparation method of compound 9 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 2-(4-bromo-phenoxy)phenylhydrazine. A yellow solid is obtained by drying with a yield of 63% and mp: 195-197°C.

[0084] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.42 (s, 1H, NH), 8.74 (s, 2H, NH2), 8.36 (s, 1H, pyrimidine-H), 8.21 (s, 1H, CH=N), 7.54 (d, J=8.8Hz, 2H, Ar-H),7.32(d,J=8.0Hz,1H,Ar-H),7.18(t,J=7.6Hz,1H,Ar-H),6.93(m,3H,Ar-H),6.85(dd,J=15.3,8.0Hz,1H,Ar-H),2.50(s,3H,CH3);

[0085] HRMS(ESI):calcd.for C 18 H17 BrN5O[M+H] + 398.0611,found:398.0611.

[0086] Example 10

[0087]

[0088] The preparation method of compound 10 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 2-(4-methylphenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 56% and an mp of 190-191°C.

[0089] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.00 (s, 1H, NH), 8.22 (s, 1H, pyrimidine-H), 8.09 (s, 1H, CH=N), 7.79 (s, 2H, NH2), 7.24 (d, J=7.9Hz, 1H, Ar-H), 7.1 7(d,J=8.1Hz,2H,Ar-H),7.10(t,J=6.8Hz,1H,Ar-H),6.90(d,J=8.1Hz,2H,Ar-H),6.78(t,J=7.7Hz,2H,Ar-H),2.37(s,3H,CH3),2.28(s,3H,CH3);

[0090] HRMS(ESI):calcd.for C 19 H 20 N5O[M+H] + 334.1662,found:334.1660.

[0091] Example 11

[0092]

[0093] The preparation method of compound 11 is the same as that of Example 1, except that 4-phenoxyphenylhydrazine is replaced by 2-(4-tert-butyl-phenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 38% and an mp of 184-186°C.

[0094] Product structure identification data: 1H NMR (400MHz, DMSO-d6) δ (ppm): 9.99 (s, 1H, NH), 8.22 (s, 1H, pyrimidine-H), 8.1 0(s,1H,CH=N),7.80(s,2H,NH2),7.37(d,J=8.7Hz,2H,Ar-H),7.26(d,J=8.0Hz,1 H, Ar-H), 7.12 (t, J = 7.4Hz, 1H, Ar-H), 6.90 (d, J = 8.7Hz, 2H, Ar-H), 6.85 (d, J = 7. 2Hz,1H,Ar-H),6.78(t,J=7.5Hz,1H,Ar-H),2.37(s,3H,CH3),1.27(s,9H,t-Bu);

[0095] HRMS(ESI):calcd.for C 22 H 26 N5O[M+H] + 376.2132,found:376.2126.

[0096] Example 12

[0097]

[0098] The preparation method of compound 12 is the same as that of Example 1, except that 2-methyl-4-amino-5-formylpyrimidine is replaced by 2,6-dimethyl-4-amino-5-formylpyrimidine. The obtained pure product is a yellow solid with a yield of 60% and an mp of 196-198°C.

[0099] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.46 (s, 1H, NH), 8.31 (s, 1H, CH = N), 7.80 (s, 2H, NH2), 7.37 (d ,J=9.0Hz,2H,Ar-H),6.97(dt,J=13.5,9.0Hz,6H,Ar-H),2.39(s,3H,CH3),2.32(s,3H,CH3);

[0100] HRMS(ESI):calcd.for C 19 H 19 ClN5O[M+H] + 368.1273,found:368.1275.

[0101] Example 13

[0102]

[0103] The preparation method of compound 13 is the same as that of Example 1, except that 2-methyl-4-amino-5-formyl pyrimidine is replaced by 2,6-dimethyl-4-amino-5-formyl pyrimidine, and 4-phenoxyphenylhydrazine is replaced by 4-(4-bromo-phenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 62% and an mp of 154-156°C.

[0104] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.38 (s, 1H, NH), 8.28 (s, 1H, CH=N), 7.80 (s, 2H, NH2), 7.56-7.44 (m, 2H, Ar-H), 7.0 2(d,J=9.0Hz,2H,Ar-H),6.96(d,J=9.0Hz,2H,Ar-H),6.91-6.84(m,2H,Ar-H),2.39(s,3H,CH3),2.32(s,3H,CH3);

[0105] HRMS(ESI):calcd.for C 19 H 19 BrN5O[M+H] + 412.0767,found:412.0768.

[0106] Example 14

[0107]

[0108] The preparation method of compound 14 is the same as that of Example 1, except that 2-methyl-4-amino-5-formyl pyrimidine is replaced by 2,6-dimethyl-4-amino-5-formyl pyrimidine, and 4-phenoxyphenylhydrazine is replaced by 4-(4-tert-butyl-phenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 60% and an mp of 143-145°C.

[0109] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.64 (s, 1H, NH), 8.56 (s, 1H, CH = N), 8.25 (s, 2H, NH2), 7.37 (d, J = 8.6Hz, 2H, A r-H),7.01(m,4H,Ar-H),6.87(d,J=8.6Hz,2H,Ar-H),2.50(s,3H,CH3),2.45(s,3H,CH3),1.29(s,9H,t-Bu);

[0110] HRMS(ESI):calcd.for C 23H 28 N5O[M+H] + 390.2288,found:390.2284.

[0111] Example 15

[0112]

[0113] The preparation method of compound 15 is the same as that of Example 1, except that 2-methyl-4-amino-5-formylpyrimidine is replaced by 2,6-dimethyl-4-amino-5-formylpyrimidine, and 4-phenoxyphenylhydrazine is replaced by 4-(2-chloro-4-trifluoromethylphenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 56% and an mp of 147-149°C.

[0114] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.63 (s, 1H, NH), 8.30 (s, 1H, CH=N), 8.15 (s, 2H, NH2), 7.98 (s, 1H, Ar-H), 7.65 (d, J=8.7Hz, 1H, A r-H),7.11(d,J=8.9Hz,2H,Ar-H),7.02(d,J=8.9Hz,2H,Ar-H),6.95(d,J=8.7Hz,1H,Ar-H),2.45(s,3H,CH3),2.38(s,3H,CH3);

[0115] HRMS(ESI):calcd.for C 20 H 18 ClF3N5O[M+H] + 436.1146,found:436.1164.

[0116] Example 16

[0117]

[0118] The preparation method of compound 16 is the same as that of Example 1, except that 2-methyl-4-amino-5-formaldehyde pyrimidine is replaced by 2,6-dimethyl-4-amino-5-formaldehyde pyrimidine, and 4-phenoxyphenylhydrazine is replaced by 4-(2-chlorophenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 47% and an mp of 206-208°C.

[0119] Product structure identification data: 1H NMR (400MHz, DMSO-d6) δ (ppm): 10.51 (s, 1H, NH), 8.20 (m, 3H, CH = N, NH2), 7.55 (dd, J = 8.0, 1.5Hz, 1H, Ar-H), 7.35-7.22 (m, 1H, Ar -H),7.11(td,J=7.9,1.4Hz,1H,Ar-H),6.98(m,4H,Ar-H),6.89(dd,J=8.2,1.3Hz,1H,Ar-H),2.43(s,3H,CH3),2.37(s,3H,CH3);

[0120] HRMS(ESI):calcd.for C 19 H 19 ClN5O[M+H] + 368.1273,found:368.1270.

[0121] Example 17

[0122]

[0123] The preparation method of compound 17 is the same as that of Example 1, except that 2-methyl-4-amino-5-formyl pyrimidine is replaced by 2,6-dimethyl-4-amino-5-formyl pyrimidine, and 4-phenoxyphenylhydrazine is replaced by 4-(4-methoxyphenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 67% and an mp of 179-181°C.

[0124] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.29 (s, 1H, NH), 8.25 (s, 1H, CH = N), 7.81 (s, 2H, NH2),6.91(m,8H,Ar-H),3.72(s,3H,OCH3),2.39(s,3H,CH3),2.32(s,3H,CH3);

[0125] HRMS(ESI):calcd.for C 20 H 22 N5O[M+H] + 364.1768,found:364.1769.

[0126] Example 18

[0127]

[0128] The preparation method of compound 18 is the same as that of Example 1, except that 2-methyl-4-amino-5-formylpyrimidine is replaced by 2,6-dimethyl-4-amino-5-formylpyrimidine, and 4-phenoxyphenylhydrazine is replaced by 4-(3-chlorophenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 52% and an mp of 157-159°C.

[0129] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.44 (s, 1H, NH), 8.30 (s, 1H, CH=N), 7.80 (s, 2H, NH2), 7 .36(t,J=8.1Hz,1H,Ar-H),7.15-6.84(m,7H,Ar-H),2.39(s,3H,CH3),2.32(s,3H,CH3);

[0130] HRMS(ESI):calcd.for C 19 H 19 ClN5O[M+H] + 368.1273,found:368.1275.

[0131] Example 19

[0132]

[0133] The preparation method of compound 19 is the same as that of Example 1, except that 2-methyl-4-amino-5-formaldehyde pyrimidine is replaced by 2,6-dimethyl-4-amino-5-formaldehyde pyrimidine, and 4-phenoxyphenylhydrazine is replaced by 2-phenoxyphenylhydrazine. The obtained pure product is a yellow solid with a yield of 56% and an mp of 182-184°C.

[0134] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.41 (s, 1H, NH), 9.22 (s, 2H, NH2), 8.56 (s, 1H, CH = N), 7.39 (t, J = 7.9Hz, 2H, Ar-H), 7.30 (d, J = 7.9Hz, 1 H,Ar-H),7.15(dt,J=14.8,4.8Hz,2H,Ar-H),7.01(d,J=7.9Hz,2H,Ar-H),6.91-6.81(m,2H,Ar-H),2.54(s,3H,CH3),2.53(s,3H,CH3);

[0135] HRMS(ESI):calcd.for C 19 H 20 N5O[M+H]+ 334.1662,found:334.1660.

[0136] Example 20

[0137]

[0138] The preparation method of compound 20 is the same as that of Example 1, except that 2-methyl-4-amino-5-formylpyrimidine is replaced by 2,6-dimethyl-4-amino-5-formylpyrimidine, and 4-phenoxyphenylhydrazine is replaced by 2-(4-chlorophenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 63% and an mp of 192-193°C.

[0139] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.13 (s, 1H, NH), 8.60 (s, 1H, CH = N), 8.25 (s, 2H, NH2), 7.43 (d, J = 8.9Hz, 2H, Ar-H), 7.26 (d, J = 7.4Hz, 1H, Ar-H), 7.17 (t ,J=7.4Hz,1H,Ar-H),7.01(d,J=8.9Hz,2H,Ar-H),6.91(d,J=7.1Hz,1H,Ar-H),6.82(dd,J=11.1,4.1Hz,1H,Ar-H),2.41(s,3H,CH3),2.38(s,3H,CH3);

[0140] HRMS(ESI):calcd.for C 19 H 19 ClN5O[M+H] + 368.1273,found:368.1270.

[0141] Example 21

[0142]

[0143] Compound 21 was prepared as in Example 1, except that 2-methyl-4-amino-5-formylpyrimidine was replaced with 2,6-dimethyl-4-amino-5-formylpyrimidine, and 4-phenoxyphenylhydrazine was replaced with 2-(4-bromophenoxy)phenylhydrazine. The resulting pure product was a yellow solid. Yield: 58%, mp: 189-191°C.

[0144] Product structure identification data: 1H NMR (400MHz, DMSO-d6) δ (ppm): 10.20 (s, 1H, NH), 8.55 (m, 3H, CH = N, NH2), 7.55 (d, J = 8.8Hz, 2H, Ar-H), 7.27 (d, J = 7.9Hz, 1H, A r-H),7.18(t,J=7.7Hz,1H,Ar-H),6.94(m,8.5Hz,3H,Ar-H),6.84(t,J=7.6Hz,1H,Ar-H),2.44(s,3H,CH3),2.42(s,3H,CH3);

[0145] HRMS(ESI):calcd.for C 19 H 19 BrN5O[M+H] + 412.0767,found:412.0767.

[0146] Example 22

[0147]

[0148] The preparation method of compound 22 is the same as that of Example 1, except that 2-methyl-4-amino-5-formyl pyrimidine is replaced by 2,6-dimethyl-4-amino-5-formyl pyrimidine, and 4-phenoxyphenylhydrazine is replaced by 2-(4-methylphenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 63% and an mp of 187-189°C.

[0149] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 10.59 (s, 1H, NH), 8.56 (s, 2H, NH2), 8.21 (s, 1H, CH = N), 7.14 (d, J = 8.3Hz, 2H, Ar-H),6.97(m,4H,Ar-H),6.82(d,J=8.3Hz,2H,Ar-H),2.48(s,3H,CH3),2.43(s,3H,CH3),2.26(s,3H,CH3);

[0150] HRMS(ESI):calcd.for C 20 H 22 N5O[M+H] + 348.1819,found:348.1815.

[0151] Example 23

[0152]

[0153] The preparation method of compound 23 is the same as that of Example 1, except that 2-methyl-4-amino-5-formaldehyde pyrimidine is replaced by 2,6-dimethyl-4-amino-5-formaldehyde pyrimidine, and 4-phenoxyphenylhydrazine is replaced by 2-(4-tert-butylphenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 58% and an mp of 206-208°C.

[0154] Product structure identification data: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 9.98 (s, 1H, NH), 8.63 (s, 1H, CH = N), 7.84 (s, 2H, NH2),7.38(d,J=8.7Hz,2H,Ar-H),7.23(d,J=7.9Hz,1H,Ar-H),7.12(t,J=7.6H z,1H,Ar-H),6.91(d,J=8.7Hz,2H,Ar-H),6.87-6.80(m,1H,Ar-H),6.77(dd,J= 11.0,4.2Hz,1H,Ar-H),2.35(s,3H,CH3),2.32(s,3H,CH3),1.27(s,9H,t-Bu);

[0155] HRMS(ESI):calcd.for C 23 H 28 N5O[M+H] + 390.2288,found:390.2285.

[0156] Example 24

[0157]

[0158] The preparation method of compound 24 is the same as that of Example 1, except that 2-methyl-4-amino-5-formyl pyrimidine is replaced by 2,6-dimethyl-4-amino-5-formyl pyrimidine, and 4-phenoxyphenylhydrazine is replaced by 2-(4-methoxyphenoxy)phenylhydrazine. The obtained pure product is a yellow solid with a yield of 67% and an mp of 215-217°C.

[0159] Product structure identification data: 1H NMR (400MHz, DMSO-d6) δ (ppm): 10.06 (s, 1H, NH), 8.69 (s, 1H, CH=N), 7.71 (s, 2H, NH2), 7.21 (d, J=7.9Hz, 1H, Ar-H), 7.08 ( t,J=6.5Hz,1H,Ar-H),7.01(m,4H,Ar-H),6.78-6.70(m,2H,Ar-H),3.77(s,3H,OCH3),2.39(s,3H,CH3),2.35(s,3H,CH3);

[0160] HRMS(ESI):calcd.for C 20 H 22 N5O2[M+H] + 364.1768,found:364.1764.

[0161] Example 25

[0162] The preparation method of compound 2 comprises the following steps: dissolving 2 mmol of 2-methyl-4-amino-5-formaldehyde pyrimidine and 3 mmol of 4-(4-chloro-phenoxy)phenylhydrazine in 15 mL of acetonitrile, adding 0.3 mmol of ascorbic acid, heating under reflux with stirring for 48 hours, and monitoring the reaction progress by TLC. After the reaction is completed, 20 ml of water is added, and a solid precipitates under stirring. The solid is filtered and dried to obtain a yellow solid with a yield of 60%.

[0163] Example 26

[0164] The preparation method of compound 3 comprises the following steps: dissolving 2 mmol of 2-methyl-4-amino-5-formaldehyde pyrimidine and 2.5 mmol of 4-(4-bromo-phenoxy)phenylhydrazine in 15 mL of 1,2-dichloroethane, adding 0.05 mmol of tartaric acid, heating under reflux with stirring to react for 3 hours, and monitoring the reaction progress by TLC. After the reaction is completed, 20 ml of water is added, and solid precipitates during stirring. The solid is filtered and dried to obtain a yellow solid. The obtained pure product is a yellow solid with a yield of 58%.

[0165] Example 27

[0166] The preparation method of compound 4 comprises the following steps: dissolving 2 mmol of 2-methyl-4-amino-5-formaldehyde pyrimidine and 2 mmol of 4-(4-methylphenoxy)phenylhydrazine in 15 mL of acetone, adding 0.1 mmol of trifluoroacetic acid, heating under reflux with stirring for 6 hours, and monitoring the reaction progress by TLC. After the reaction is completed, 20 ml of water is added, and a solid precipitates after stirring. The solid is filtered and dried to obtain a yellow solid with a yield of 53%.

[0167] Example 28

[0168] The preparation method of compound 5 comprises the following steps: dissolving 1 mmol of 2-methyl-4-amino-5-formaldehyde pyrimidine and 1.5 mmol of 4-(2,4-dichlorophenoxy)phenylhydrazine in 15 mL of tert-butanol, adding 0.08 mmol of formic acid, heating under reflux and stirring to react for 8 hours, monitoring the reaction progress by TLC, adding 20 ml of water after the reaction is completed, stirring to precipitate a solid, filtering, and drying to obtain a yellow solid, with a yield of 45%.

[0169] Example 29

[0170] The preparation method of compound 6 comprises the following steps: dissolving 3 mmol of 2-methyl-4-amino-5-formaldehyde pyrimidine and 4 mmol of 4-(2-chloro-4-trifluoromethylphenoxy)phenylhydrazine in 15 mL of toluene, adding 0.3 mmol of salicylic acid, heating under reflux with stirring for 12 hours, and monitoring the reaction progress by TLC. After the reaction is completed, 20 ml of water is added, and a solid precipitates after stirring. The solid is filtered and dried to obtain a yellow solid with a yield of 40%.

[0171] Example 30

[0172] The preparation method of compound 7 comprises the following steps: dissolving 2 mmol of 2-methyl-4-amino-5-formylpyrimidine and 2.2 mmol of 2-phenoxyphenylhydrazine in 15 mL of ethyl acetate, adding 0.02 mmol of malic acid, heating under reflux with stirring for 6-8 hours, and monitoring the reaction progress by TLC. After the reaction is completed, 20 ml of water is added, and a solid precipitates after stirring. The solid is filtered and dried to obtain a yellow solid with a yield of 53% and an mp of 195-197°C.

[0173] Example 31

[0174] The preparation method of compound 8 comprises the following steps: dissolving 1.8 mmol of 2-methyl-4-amino-5-formaldehyde pyrimidine and 2 mmol of 2-(4-chloro-phenoxy)phenylhydrazine in 15 mL of tetrahydrofuran, adding 0.02 mmol of glacial acetic acid, heating under reflux with stirring for 6-8 hours, and monitoring the reaction progress by TLC. After the reaction is completed, 20 ml of water is added, and a solid precipitates by stirring. The solid is filtered and dried to obtain a yellow solid with a yield of 55%.

[0175] Bactericidal activity test

[0176] Test materials: peach brown rot fungus, apple ring rot fungus, pepper phytophthora, fusarium head blight, pythium rot, rapeseed sclerotinia, dollar spot fungus. Test method: The compound prepared in the example of the present invention and comparative compound 1 (D1), comparative compound 2 (D2), and comparative compound 3 (D3) were dissolved in DMSO to prepare a series of drug solutions (concentration 50ppm), which were added to the potato culture medium cooled to about 45°C after melting to prepare drug-containing plates with the required drug concentration. A 5mm diameter bacterial cake was taken from the edge of the colony of each strain pre-cultured on the PDA flat culture medium, inoculated on the drug-containing plates with different concentrations, and cultured in the dark at 25°C. When the diameter of the control colony reached more than 80% of the diameter of the culture dish, the colony diameter was measured by the cross-cross method. Each treatment was repeated 3 times, and the DMSO solution was used as the blank control. The percentage (%) of inhibition of hyphae growth by each drug concentration was calculated according to the following formula. The inhibition of the compounds of the present invention, comparative compounds and carbendazim on each pathogenic fungus EC 50 The measurement results are shown in Table 2.

[0177]

[0178]

[0179] Table 1: Activity data of some compounds of the present invention and comparative compounds against apple ring rot pathogen (test concentration 50 ppm)

[0180]

[0181]

[0182] Table 2: Activity data of some compounds of the present invention and comparative compounds against dollar spot pathogen (test concentration 50 ppm)

[0183] Compound Inhibition rate (%) Compound Inhibition rate (%) D1 41 12 83 D2 33 13 81 D3 29 14 68 1 85 15 80 2 80 16 91 3 81 17 86 4 85 18 72 5 90 19 81 6 84 20 83 9 80 21 80 10 86 22 86 11 78

[0184] Table 3: Activity data of some compounds of the present invention and comparative compounds against peach brown rot fungus (test concentration 50 ppm)

[0185] Compound Inhibition rate (%) Compound Inhibition rate (%) D1 84 13 70 D2 86 14 62 D3 87 15 71 12 74 19 56

[0186] Table 4: Activity data of some compounds of the present invention and comparative compounds against Phytophthora capsici (test concentration 50 ppm)

[0187]

[0188]

[0189] Table 5: Activity data of some compounds of the present invention and comparative compounds against Gibberella (test concentration 50 ppm)

[0190] Compound Inhibition rate (%) Compound Inhibition rate (%) D1 44 5 61 D2 53 6 57 D3 55 12 56 2 55 13 64 3 54 21 82

[0191] Table 6: Activity data of some compounds of the present invention and comparative compounds against Sclerotinia sclerotiorum (test concentration 50 ppm)

[0192] Compound Inhibition rate (%) Compound Inhibition rate (%) D1 15 11 91 D2 29 12 95 D3 30 13 93 1 88 14 82 2 73 16 92 3 75 17 85 4 77 19 86 5 69 20 88 7 70 21 96 8 75 22 83 9 96 23 63 10 83

[0193] Table 7: Activity data of some compounds of the present invention and comparative compounds against Pythium spp. (test concentration 50 ppm)

[0194] Compound Inhibition rate (%) Compound Inhibition rate (%) D1 28 12 81 D2 47 13 66 D3 39 16 83

[0195] As can be seen from Tables 1-7, the 4-aminopyrimidinehydrazone compounds containing diphenyl ether groups based on the present invention have certain inhibitory activity against apple ring spot fungus, dollar spot fungus, peach brown rot fungus, pepper phytophthora, fusarium head blight fungus, rapeseed sclerotinia fungus, and pythium fungus. Compared with D1, D2, and D3, the target compounds 1-24 obtained after introducing diphenyl ether structural units into the 4-aminopyrimidinehydrazone compounds have better fungicidal activity, especially showing excellent inhibitory activity against rapeseed sclerotinia fungus and dollar spot fungus.

[0196] Table 8: Bactericidal activity data of the compounds of the present invention, comparative compounds and carbendazim (EC 50 ,μg / mL)

[0197] serial number Dollar spot fungus Sclerotinia sclerotiorum serial number Dollar spot fungus Sclerotinia sclerotiorum D1 179.30 138.56 12 0.74 0.14 D2 207.12 99.38 13 15.63 2.81 D3 156.25 207.17 14 36.32 38.91 1 0.70 1.26 16 1.93 4.12 2 0.41 11.60 17 0.50 0.83 3 0.83 24.03 19 5.48 21.67 4 0.73 2.40 20 0.44 5.30 5 1.23 5.06 21 4.30 2.81 9 2.12 66.82 22 5.43 6.62 10 4.62 21.21 Carbendazim 1.66 >100 11 1.22 1.00

[0198] As can be seen from Table 8, the compounds of the present invention have a strong inhibitory effect on both dollar spot pathogen and rapeseed sclerotinia pathogen, and the inhibitory effect is much better than that of the comparative compounds D1, D2 and D3, and the inhibitory activity against rapeseed sclerotinia pathogen is significantly higher than that of the control drug carbendazim. For example, the inhibitory activity of compound 12 against rapeseed sclerotinia pathogen is more than 700 times higher than that of carbendazim; the inhibitory activity against dollar spot pathogen is also generally higher than that of the control drug carbendazim. For example, the inhibitory activity of compounds 1, 2, 3, 4, 11, 12, 17 and 20 of the present invention against the two pathogenic fungi is higher than that of the control drug carbendazim, among which the inhibitory activity of compounds 2, 17 and 20 against dollar spot pathogen is more than 3 times higher than that of carbendazim, showing good application value.

[0199] Definitions and explanations of terms in this invention:

[0200] “C1-10 alkyl” is understood to mean preferably a straight-chain or branched saturated monovalent hydrocarbon radical having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, isopentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 1,2-dimethylpropyl, neopentyl, 1,1-dimethylpropyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 2-ethylbutyl, 1-ethylbutyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 2,3-dimethylbutyl, 1,3-dimethylbutyl or 1,2-dimethylbutyl, or the like, or isomers thereof. C1-6 alkyl has 1, 2, 3, 4, 5 or 6 carbon atoms, such as methyl, ethyl, propyl, butyl, isopropyl, isobutyl, sec-butyl, tert-butyl; C1-3 alkyl has 1, 2 or 3 carbon atoms, such as methyl, ethyl, n-propyl or isopropyl, and C1-4 alkyl has 1, 2, 3 or 4 carbon atoms.

[0201] Unless otherwise indicated, when "compounds of the present invention" or "compounds of the present invention" are used herein, it is intended to cover the compound represented by formula (I), its stereoisomers, geometric isomers, tautomers, racemates, nitrogen oxides, hydrates, solvates, and pharmaceutically acceptable salts.

[0202] As used herein, all stereoisomers of the compounds of the present invention (whether in mixture or pure or substantially pure form) are taken into account. The term "stereoisomer" as used herein may include compounds that are optical isomers by possessing one or more chiral atoms, as well as compounds that are optical isomers by restricted rotation around one or more bonds. The definition of the compounds of the present invention encompasses all possible stereoisomers and mixtures thereof. Racemic forms and isolated optical isomers with specific activity are very specifically encompassed. The racemic form can be resolved by physical methods, including but not limited to fractional crystallization, separation or crystallization of diastereomeric derivatives, or separation by chiral column chromatography. Individual optical isomers can be obtained from the racemate by conventional methods, including but not limited to salt formation with an optically active acid, followed by crystallization.

[0203] Term used in the present invention, compound shown in formula I and salt thereof can exist by their tautomeric form, and in described tautomeric form, hydrogen atom is transferred to other parts of molecule, and therefore the chemical bond between atom in molecule is rearranged.Should be understood that all tautomeric forms (as long as they can exist) are all included in the present invention.In addition, compound shown in formula I of the present invention can have trans isomer and cis isomer.

[0204] The term "chemically acceptable salt" used in the present invention refers to a salt formed by the reaction of the compound represented by Formula I with an inorganic acid or an organic acid.

[0205] The term "contact" used herein should be understood in a broad sense, and can be any manner that allows at least two reactants to undergo a chemical reaction, such as mixing the two reactants under appropriate conditions.

[0206] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to the embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the claims and their equivalents.

Claims

1. A 4-aminopyrimidinehydrazone compound containing a diphenyl ether group, characterized in that: The compound is a compound represented by Formula I or a pharmaceutically acceptable salt of the compound represented by Formula I: Among them, R 1 is hydrogen or methyl; R 2 is a single or multiple substituted group on the benzene ring, R 2 When it is a multi-substituted group, each group in the multi-substituted group is independently selected from halogen, C 1-10 Alkyl, -CF3 or alkoxy, R 2 When it is a monosubstituted group, R 2 Selected from halogen, -CF3, C 1-10 Alkyl or alkoxy.

2. The 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to claim 1, wherein The halogen is fluorine, chlorine, bromine or iodine.

3. The 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to claim 1, wherein The R 2 Selected from C 1-4 alkyl.

4. The 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to claim 1, wherein The alkoxy group is C 1-6 Alkoxy.

5. The 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to claim 1, wherein The compound is the following compound or a pharmaceutically acceptable salt thereof:

6. The method for preparing a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to any one of claims 1 to 5, wherein: In the presence of an acid catalyst, the compound represented by Formula II and the compound represented by Formula III are dissolved in a first organic solvent, and heated at 60 to 90 degrees Celsius to react to obtain the compound represented by Formula I.

7. The method for preparing a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to claim 6, wherein the first organic solvent is at least one selected from acetonitrile, ethanol, 1,2-dichloroethane, acetone, tert-butanol, toluene, benzene, xylene, ethyl acetate, methanol, n-hexane, dichloromethane, chloroform, tetrahydrofuran, dimethyl sulfoxide, and N,N-dimethylformamide.

8. The method according to claim 6, characterized in that The acid catalyst is selected from at least one of ascorbic acid, acetic acid, tartaric acid, trifluoroacetic acid, formic acid, salicylic acid, and malic acid.

9. The method for preparing a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to any one of claims 6 to 8, characterized in that: The molar ratio of the compound represented by formula II to the compound represented by formula III and the acid catalyst is 1:(1-1.5):(0.01-0.15).

10. The method for preparing a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to any one of claims 6 to 8, characterized in that: The temperature of the heating reaction is 64 to 78 degrees Celsius.

11. The method for preparing a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to any one of claims 6 to 8, characterized in that: The heating reaction time is 2 to 60 hours.

12. The method for preparing a 4-aminopyrimidinehydrazone compound containing a diphenyl ether group according to any one of claims 6 to 8, characterized in that: The heating reaction time is 3 to 48 hours.

13. A pesticide, characterized in that The invention comprises the 4-aminopyrimidinehydrazone compound containing a diphenyl ether group as described in any one of claims 1 to 5.

14. A method for preventing or treating plant diseases, characterized in that: Applying the diphenyl ether group-containing 4-aminopyrimidinehydrazone compound according to any one of claims 1 to 5 to plants or applying the pesticide according to claim 13 to plants.

15. The method according to claim 14, characterized in that The plant disease is caused by at least one of peach brown rot fungus, apple ring rot fungus, pepper phytophthora, fusarium sclerotinia, pythium sclerotiorum, rapeseed sclerotinia and dollar spot fungus.

16. The method according to claim 14, characterized in that The plant disease is caused by one of the pathogens of dollar spot or Sclerotinia sclerotiorum.

17. The method according to claim 14, characterized in that The plant is apple, peach or rapeseed.

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