Application of compounds containing phenylthiazole acylhydrazone structure as agricultural fungicides in plant disease control

Abstract

The present invention discloses the use of compounds containing a phenylthiazole acylhydrazone structure as agricultural fungicides for plant disease control. The general structural formula of the compound is shown in Formula (I), wherein R1 and R2 are independently unsubstituted, monosubstituted, or disubstituted, and the substituents are selected from hydrogen, halogen, C1-C8 straight-chain or branched alkyl, hydroxyl, amino, nitro, thiol, carboxyl, cyano, ester, ketone, aldehyde, trifluoromethyl, trifluoromethoxy, C1-C8 alkoxy, C1-C8 straight-chain or branched alkyl substituted with 1-3 halogens, C1-C8 straight-chain or branched alkoxy substituted with 1-3 halogens, aryl, and heterocyclic groups. Experiments have shown that the compounds provided by the present invention have strong fungicidal activity against plant pathogenic fungi and bacteria and have the potential to be developed and applied as new agricultural fungicides and bactericides. #imgabs0#

Description

Technical Field

[0001] The present invention belongs to the technical field of pesticides, and in particular relates to the application of a class of compounds containing a phenylthiazole acylhydrazone structure as agricultural fungicides and bactericides in the prevention and treatment of plant diseases. Background Art

[0002] The thiazole ring is an important five-membered aromatic heterocycle containing nitrogen and sulfur heteroatoms. It easily forms hydrogen bonds with other molecules and easily coordinates with metal ions. It has broad application prospects in many fields such as pesticides and medicine. This type of compound has multiple pharmacological activities such as bactericidal, insecticidal, anti-inflammatory, and antiviral. In the field of agricultural fungicide research and development, the thiazole structure has attracted much attention due to its good antifungal, antibacterial and antiviral activities and low toxicity to humans. Several commercial fungicides have been successfully developed: ethaboxam, thiabendazole, thifluzamide, etc. (Journal of Heterocyclic Chemistry, 2020, 57, 2304-2329.).

[0003] Natural products have novel chemical structures, unique targets, and a broad spectrum of biological activity, making them an important source of pesticide lead compounds (Bioorganic & Medicinal Chemistry, 2009, 17, 40-22). For example, phenazine-1-carboxylic acid (PCA) is a secondary metabolite produced by Pseudomonas rhizosphericus. It is safe, environmentally friendly, highly effective, and has a broad bactericidal spectrum. It has been registered for use against various crop diseases, including rice blast and pepper blight (Chinese Journal of Pesticide Science, 2014, 16.4:387-393). Thiasporine A was discovered in 2015 in the marine actinomycete Actinomycetospora. chlorine A natural product containing a thiazole structure was discovered in the metabolites of SNC-032. In previous work, the inventors first reported the agricultural activity of thiasporine A and found that its analogs possessed strong agricultural fungicidal activity. Some of these compounds exhibited strong inhibitory effects against rice sheath blight, white rot of Bletilla striata, tobacco blackstem disease, and rapeseed blackstem disease, exceeding those of the commercial control agent, thiafluamide (Chinese Journal of Pesticide Science, 2022, 24.2:280-288). Previous research results suggest that the phenylthiazole skeleton has the potential to become a lead structure for agricultural fungicides.

[0004] The acylhydrazone structure (-CONHN=CH-) contains two active substructures: an amide and a Schiff base. These unique structural features give it excellent biological activities, including antifungal, antibacterial, insecticidal, herbicidal, anticancer, and anti-inflammatory properties. It has broad applications in pesticide and pharmaceutical research (Pest Management Science, 2023, 79.2:655-665). Currently, in pesticide research and development, commercial fungicides containing acylhydrazone structures include quinone oxime hydrazone (Benquinox), which is primarily used to control rice rot, cotton mildew, and other fungal diseases. Summary of the Invention

[0005] The present invention aims to find a more efficient and broad-spectrum agricultural fungicide.

[0006] To achieve this objective, the present invention designed and synthesized a series of compounds containing phenylthiazole acylhydrazones by introducing an acylhydrazone fragment into the phenylthiazole backbone based on the principle of active substructure splicing. Experimental results indicate that these compounds exhibit strong fungicidal activity against plant pathogenic fungi and bacteria, demonstrating their potential as novel agricultural fungicides and bactericides.

[0007] The technical solutions of the present invention are as follows:

[0008] A compound containing a phenylthiazole acylhydrazone structure, wherein the structural formula of the compound is shown in formula (I):

[0009]

[0010] In formula (I), R1 and R2 are each independently unsubstituted, monosubstituted or disubstituted, and their substituents are selected from hydrogen, halogen, C1-C8 straight-chain or branched alkyl, hydroxyl, amino, nitro, mercapto, carboxyl, cyano, ester, keto, aldehyde, trifluoromethyl, trifluoromethoxy, C1-C8 alkoxy, C1-C8 straight-chain or branched alkyl substituted by 1-3 halogens, C1-C8 straight-chain or branched alkoxy substituted by 1-3 halogens, aryl, and heterocyclic group.

[0011] The present invention provides a method for synthesizing the above-mentioned compound containing a phenylthiazole acylhydrazone structure, which specifically comprises the following steps:

[0012] S1. dissolving the compound represented by formula (II) in an organic solvent, and then adding magnesium chloride and sodium hydrosulfide to react, and after the reaction is completed, obtaining an intermediate product A represented by formula (III);

[0013] S2, heating the intermediate product A and ethyl 3-bromopyruvate to reflux, extracting the reaction solution to obtain the intermediate product B represented by formula (IV);

[0014] S3, heating the intermediate product B and hydrazine hydrate under reflux to react, to obtain the intermediate product C represented by formula (V);

[0015] S4, dissolving the intermediate product C in ethanol, adding compound (VI) and acetic acid, and heating under reflux to obtain the final product;

[0016]

[0017] In the above structural formula, R1 is unsubstituted (i.e., R1 is hydrogen) or monosubstituted or disubstituted, and its substituents are selected from halogen, C1-C8 straight-chain or branched alkyl, hydroxyl, amino, nitro, thiol, carboxyl, cyano, ester, keto, aldehyde, trifluoromethyl, trifluoromethoxy, C1-C8 alkoxy, C1-C8 straight-chain or branched alkyl substituted with 1-3 halogens, C1-C8 straight-chain or branched alkoxy substituted with 1-3 halogens, aryl, and heterocyclic groups;

[0018] R2 is unsubstituted (i.e., R2 is hydrogen) or monosubstituted or disubstituted, and its substituents are selected from halogen, C1-C8 straight-chain or branched alkyl, hydroxyl, amino, nitro, thiol, carboxyl, cyano, ester, keto, aldehyde, trifluoromethyl, trifluoromethoxy, C1-C8 alkoxy, C1-C8 straight-chain or branched alkyl substituted by 1-3 halogens, C1-C8 straight-chain or branched alkoxy substituted by 1-3 halogens, aryl, and heterocyclic group.

[0019] Preferably, in the above preparation method, the organic solvent used in step S1 is N,N-dimethylformamide. After the reaction in step S1 is completed, the reaction solution is diluted with brine, extracted with ethyl acetate, dried, and filtered. The filtrate is desolvated to obtain intermediate product A.

[0020] Preferably, in step S2 of the above preparation method, the intermediate product A and ethyl 3-bromopyruvate are refluxed in ethanol. After the reaction is completed, the reaction solution is adjusted to alkaline, the solvent is removed, and then diluted with dichloromethane, and then extracted with saturated brine. The organic phase is dried and concentrated, and then passed through a chromatography column to obtain the intermediate product B.

[0021] Preferably, in step S3 of the above preparation method, the intermediate product B and hydrazine hydrate are refluxed in methanol. After the reaction is completed, water is added to precipitate the solid, which is then filtered to obtain the intermediate product C.

[0022] Preferably, in step S4 of the above preparation method, after the reflux is completed, the reaction solution is cooled to room temperature, filtered, and then recrystallized with ethanol to obtain the final product.

[0023] The preferred synthetic route of the compound containing the phenylthiazole acylhydrazone structure is as follows:

[0024]

[0025] The compound containing a phenylthiazole acylhydrazone structure provided by the present invention has strong bactericidal activity against plant pathogenic fungi and plant pathogenic bacteria, and can be used to prepare products for preventing and treating agricultural plant diseases.

[0026] Agricultural plant diseases are fungal and / or bacterial diseases. Fungal diseases include, but are not limited to, rice blast, tea anthracnose, corn leaf spot, rapeseed sclerotinia rot, and cotton verticillium wilt. Bacterial diseases include, but are not limited to, rice bacterial blight and tomato bacterial wilt.

[0027] Specifically, when the compounds containing phenylthiazole acylhydrazone structures provided by the present invention are used to prepare fungicide and / or bactericide products, the dosage forms of the products include but are not limited to emulsifiable concentrates, aqueous emulsions, microemulsions, wettable powders, water-dispersible granules, suspensions, and the like.

[0028] Moreover, the compound containing a phenylthiazole acylhydrazone structure provided by the present invention can also be used as one of the active ingredients and compounded with one or more other substances having fungicidal activity to obtain a composite fungicide. Among them, other substances having fungicidal activity include but are not limited to azoxystrobin, pyraclostrobin, prothioconazole, mancozeb, epoxiconazole, tebuconazole, hexaconazole, prochloraz, boscalid, fluopyram, thiofuran, metalaxyl, difenoconazole, propiconazole, chlorothalonil, Jinggangmycin, carbendazim, cyanobacterium methyl, thiabendazole, blastifungin, isoblastin, tricyclazole, blastamide, kasugamycin, fosetyl-aluminum, thiophanate-copper, and thiophene-copper.

[0029] The present invention has the following beneficial effects: A novel class of compounds containing a phenylthiazole acylhydrazone structural skeleton has been designed and prepared. These compounds can be used as agricultural fungicides and bactericides for plant disease control. Experimental data demonstrates their high fungicidal activity and broad applicability. They are superior to the commercial control agents, such as pyraclostrobin, thiophanate-methyl, and sinoprolin against various fungal diseases, and superior to the commercial control agent, thiophanate-methyl, against various bacterial diseases. Therefore, these compounds have significant potential and value in the field of plant disease control. DETAILED DESCRIPTION

[0030] In order to better understand the present invention, the content of the present invention is further explained below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention.

[0031] Unless otherwise specified, all examples were prepared under conventional experimental conditions or the conditions recommended by the manufacturer's instructions. All reagents and materials used were commercially available unless otherwise specified.

[0032] Example 1

[0033] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(o-tolyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0034]

[0035] Compound 1

[0036] In compound 1, R1 and R2 are both monosubstituted and are methyl. The preparation process of the compound is as follows:

[0037] (1) Add 10 mmol of o-methylbenzonitrile (also known as 2-methylbenzonitrile) to a 100 mL single-necked reaction flask, add 30 mL of N,N-dimethylformamide, and stir until the solid is completely dissolved. Add 10 mmol of magnesium chloride hexahydrate at room temperature and stir until it is completely dissolved. Then add 20 mmol of sodium hydrosulfide monohydrate and react for about 16 h. TLC is used to monitor the reaction. Dilute with 70 mL of water: 10 mL of brine and extract with 4 x 50 mL of ethyl acetate. Combine the organic phases and cross-extract with brine (3 x 50 mL), dry with anhydrous sodium sulfate, filter, and remove the solvent from the filtrate to obtain a high-purity product (i.e., intermediate A). It can be used directly in the next reaction without purification.

[0038] (2) Add 10 mmol of o-methylthiobenzamide (intermediate product A) and 30 mL of anhydrous ethanol to a 100 mL single-necked reaction flask, stir until the solid is completely dissolved, add 11 mmol of ethyl 3-bromopyruvate, heat to 65°C, and reflux for about 2 h. Monitor the reaction progress by thin-layer chromatography (TLC) (V(petroleum ether):V(ethyl acetate)=3:1), and the reaction is complete. Add saturated NaHCO3 solution dropwise until the reaction solution becomes weakly alkaline. Remove the solvent from the reaction solution, add 50 mL of dichloromethane to dilute, extract with 2×50 mL of saturated brine, combine the organic phases, dry over anhydrous sodium sulfate, filter under reduced pressure, and concentrate the filtrate under reduced pressure. The concentrate is passed through a chromatography column (petroleum ether:ethyl acetate=8:1) to obtain the intermediate 2-(2-methyl)phenylthiazole-4-carboxylic acid ethyl ester (i.e., intermediate product B).

[0039] (3) Weigh 10 mmol of ethyl 2-(2-methyl)phenylthiazole-4-carboxylate into a single-necked reaction flask, add 30 mL of anhydrous methanol as solvent, heat and stir to fully dissolve it, then add 80% hydrazine hydrate (20 mmol) to the reaction system, heat and reflux for 4 h, add water to precipitate the solid, filter it, wash it with ethanol, and dry it to obtain 2-(2-methyl)phenylthiazole-4-carboxylic acid hydrazide (i.e., intermediate C) as a white solid.

[0040] (4) Weigh 5 mmol of 2-(2-methyl)phenylthiazole-4-carboxylic acid hydrazide and place it in a 25 mL single-necked reaction flask. Add 20 mL of ethanol as solvent and stir to fully dissolve it. Then add 5.5 mmol of p-methylbenzaldehyde and dropwise add glacial acetic acid. Heat under reflux for 5 h to stop the reaction. Cool to room temperature, filter, and recrystallize from ethanol to obtain compound 1.

[0041] The product was a white solid with a yield of 69% and an mp of 146.6~148.6℃. 1 H NMR (400 MHz, CDCl3) δ 10.32 (s, 1H), 8.32 (s, 1H), 8.24 (s, 1H), 7.71 (t, J = 6.8 Hz, 3H), 7.35 (tt, J = 14.7, 7.4 Hz, 3H), 7.22 (d, J = 7.9 Hz, 2H), 2.62 (s, 3H), 2.38 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 168.17, 157.14, 148.95, 148.83, 140.97, 136.59, 131.99,131.67, 130.94, 130.19, 130.00, 129.43, 127.85, 126.35, 125.00, 21.52, 21.49. HRMS(ESI) calcd forC 19 H 17 N3OS[M+H] + : 336.1165, found 336.1162.

[0042] Example 2

[0043] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-chlorobenzylidene)-2-(o-tolyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0044]

[0045] Compound 2

[0046] In compound 2, R1 is monosubstituted and the substituent is methyl, and R2 is monosubstituted and the substituent is Cl. The preparation method of compound 2 is similar to Example 1, except that p-tolualdehyde added in step (4) is replaced with p-chlorobenzaldehyde to obtain compound 2.

[0047] The product obtained in this example was a white solid with a yield of 74% and an mp of 137.3~139.4℃. 1 H NMR (400 MHz, DMSO- d 6) δ 11.80 (s, 1H), 8.60 (d, J = 7.2 Hz, 2H), 7.89 (d, J = 7.6 Hz, 1H), 7.75(d, J = 8.8 Hz, 2H), 7.53 (d, J = 8.4 Hz, 2H), 7.40 (dt, J = 20.0, 7.6 Hz, 3H), 2.59 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 167.57, 157.56, 149.25, 148.05,136.71, 135.08, 133.75, 132.34, 131.95, 130.65, 130.36, 129.45, 129.27,126.94, 126.86, 21.59. HRMS(ESI) calcd forC 18 H 14 ClN3OS[M+H] + : 356.0619, found356.0618.

[0048] Example 3

[0049] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-phenylthiazole-4-acylhydrazone, and its structural formula is as follows:

[0050]

[0051] Compound 3

[0052] In compound 3, R1 is unsubstituted, i.e., R1 is hydrogen, and R2 is monosubstituted, and the substituent is methyl. The preparation method of compound 3 is similar to Example 1, except that the o-methylbenzonitrile added in step (1) is replaced with unsubstituted benzonitrile to obtain compound 3.

[0053] The product obtained in this example is a white solid with a yield of 70% and an mp of 177.4-179.1°C. H NMR (400 MHz, CDCl3) δ 10.38 (s, 1H), 8.28 (d, J = 17.2 Hz, 2H), 7.98 (dd, J = 6.8, 3.0 Hz, 2H),7.72 (d, J = 7.6 Hz, 2H), 7.55 – 7.44 (m, 3H), 7.22 (d, J = 7.6 Hz, 2H), 2.39 (s,3H). 13 C NMR (101 MHz, CDCl3) δ 168.56, 157.04, 149.48, 148.83, 141.01, 132.66,130.91, 130.85, 129.46, 129.15, 127.87, 126.74, 124.44, 21.55. HRMS(ESI)calcd forC 18 H 15 N3OS[M+H] + : 322.1009, found 322.1008.

[0054] Example 4

[0055] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(3-methylphenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0056]

[0057] Compound 4

[0058] In compound 4, R1 and R2 are both monosubstituted and are methyl groups, but the substitution position of R1 is different from that in Example 1.

[0059] The preparation method of compound 4 is as follows: refer to Example 1, and replace o-methylbenzonitrile added in step (1) with 3-methylbenzonitrile to obtain compound 4.

[0060] The product obtained in this example was a white solid with a yield of 73% and an mp of 152.8~154.1℃. 1 H NMR (400 MHz, DMSO- d 6) δ 11.65 (s, 1H), 8.62 (s, 1H), 8.46 (s, 1H), 7.98 – 7.87 (m, 2H), 7.64(d, J = 8.0 Hz, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.36 (d, J = 7.6 Hz, 1H), 7.29 (d, J =8.0 Hz, 2H), 2.43 (s, 3H), 2.36 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 168.17,157.33, 149.98, 149.43, 140.50, 139.16, 132.89, 132.13, 131.99, 129.94,129.59, 127.64, 127.46, 125.77, 124.40, 21.50, 21.36. HRMS(ESI) calcdforC 19 H 17 N3OS[M+H] + : 336.1165, found 336.1165.

[0061] Example 5

[0062] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(4-methylphenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0063]

[0064] Compound 5

[0065] In compound 5, R1 and R2 are both monosubstituted and are methyl groups, but the substitution position of R1 is different from that in Example 1.

[0066] The preparation method of compound 5 refers to Example 1, and the o-methylbenzonitrile added in step (1) is replaced by 4-methylbenzonitrile to obtain compound 5.

[0067] The product obtained in this example was a white solid with a yield of 75% and an mp of 144.4~145.4℃. 1 H NMR (400 MHz, DMSO- d 6) δ 11.71 (s, 1H), 8.61 (s, 1H), 8.48 (s, 1H), 7.98 – 7.88 (m, 2H), 7.64(d, J = 7.6 Hz, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.37 (d, J = 7.6 Hz, 1H), 7.29 (d, J =8.0 Hz, 2H), 2.42 (s, 3H), 2.36 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 168.13,157.31, 149.90, 149.37, 140.52, 139.16, 132.84, 132.09, 132.03, 129.96,129.61, 127.65, 127.44, 125.92, 124.39, 21.53, 21.37. HRMS(ESI) calcdforC 19 H 17 N3OS[M+H] + : 336.1165, found 336.1164.

[0068] Example 6

[0069] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(2-chlorophenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0070]

[0071] Compound 6

[0072] In compound 6, R1 is monosubstituted and the substituent is Cl, and R2 is monosubstituted and the substituent is methyl.

[0073] The preparation method of compound 6 refers to Example 1, and the o-methylbenzonitrile added in step (1) is replaced by 2-chlorobenzonitrile to obtain compound 6.

[0074] The product obtained in this example was a white solid with a yield of 68% and an mp of 170.6-172.5°C. 1 H NMR (400 MHz,CDCl3) δ 10.36 (s, 1H), 8.45 – 8.15 (m, 3H), 7.71 (d, J = 8.0 Hz, 2H), 7.60 –7.49 (m, 1H), 7.46 – 7.34 (m, 2H), 7.22 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 163.91, 157.01, 148.90, 148.32, 141.00, 132.30, 131.10,131.06, 130.93, 130.91, 129.45, 127.86, 127.18, 126.04, 126.01, 21.53. HRMS(ESI) calcd forC 18 H 14 ClN3OS[M+H] + : 356.0619, found 356.0618.

[0075] Example 7

[0076] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(2-fluorophenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0077]

[0078] Compound 7

[0079] In compound 7, R1 is monosubstituted and the substituent is F, and R2 is monosubstituted and the substituent is methyl.

[0080] The preparation method of compound 7 refers to Example 1, and the o-methylbenzonitrile added in step (1) is replaced by 2-fluorobenzonitrile to obtain compound 7.

[0081] The product obtained in this example was a white solid with a yield of 72% and an mp of 169.9~172.5℃. 1 H NMR (400 MHz,CDCl3) δ10.39 (s, 1H), 8.38 – 8.27 (m, 3H), 7.71 (d, J = 8.0 Hz, 2H), 7.46 (q, J =6.0 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 7.22 (d, J = 8.0 Hz, 3H), 2.38 (s, 3H). 13 CNMR (101 MHz, CDCl3) δ 161.11 (d, J = 5.4 Hz), 160.34 (d, J = 252.8 Hz), 157.12,149.02, 148.56, 141.14, 132.10 (d, J = 8.6 Hz), 131.05, 129.58, 128.88 (d, J =2.4 Hz), 127.99, 125.86 (d, J = 8.9 Hz), 124.84 (d, J = 3.3 Hz), 120.66 (d, J =11.4 Hz), 116.52 (d, J = 21.6 Hz), 21.68. HRMS(ESI) calcd forC 18 H 14 FN3OS[M+H] + :340.0914, found 340.0913.

[0082] Example 8

[0083] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(4-fluorophenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0084]

[0085] Compound 8

[0086] In compound 8, R1 is monosubstituted and the substituent is F (the position of the substituent is different from that of compound 7), and R2 is monosubstituted and the substituent is methyl.

[0087] The preparation method of compound 8 refers to Example 1, and the o-methylbenzonitrile added in step (1) is replaced by 4-fluorobenzonitrile to obtain compound 8.

[0088] The product obtained in this example was a white solid with a yield of 66% and an mp of 180.0~181.3℃. 1 H NMR (400 MHz, DMSO- d 6) δ 11.73 (s, 1H), 8.59 (s, 1H), 8.49 (s, 1H), 8.19 (dd, J = 8.8, 5.5Hz, 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.42 (t, J = 8.8 Hz, 2H), 7.29 (d, J = 8.0 Hz,2H), 2.35 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 166.25, 163.54 (d, J = 249.0 Hz),156.72, 149.35, 148.86, 140.02, 131.53, 129.44, 129.05, 128.96, 127.13,125.57, 116.25 (d, J = 22.1 Hz), 21.01. HRMS(ESI) calcd forC 18 H 14 FN3OS[M+H] + :340.0914, found 340.0914.

[0089] Example 9

[0090] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(2-bromophenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0091]

[0092] Compound 9

[0093] In compound 9, R1 is monosubstituted and the substituent is Br, and R2 is monosubstituted and the substituent is methyl.

[0094] The preparation method of compound 9 is as follows: with reference to Example 1, except that o-methylbenzonitrile added in step (1) is replaced with 2-bromobenzonitrile to obtain compound 9.

[0095] The product obtained in this example was a white solid with a yield of 74% and an mp of 172.7~175.3℃. 1 H NMR (400 MHz,CDCl3) δ 10.35 (s, 1H), 8.41 (s, 1H), 8.27 (s, 1H), 8.01 (dd, J = 7.6, 1.6 Hz,1H), 7.78 – 7.69 (m, 3H), 7.46 (td, J = 7.6, 1.3 Hz, 1H), 7.34 (td, J = 7.6, 2.0Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 2.39 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.41,156.99, 148.81, 148.44, 141.05, 134.31, 133.15, 131.61, 131.31, 130.85,129.46, 127.88, 127.72, 126.04, 121.83, 21.57. HRMS(ESI) calcd forC 18 H 14 BrN3OS[M+H] + : 400.0114, found 400.0114.

[0096] Example 10

[0097] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(2-methoxyphenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0098]

[0099] Compound 10

[0100] In compound 10, R1 is monosubstituted and the substituent is methoxy, and R2 is monosubstituted and the substituent is methyl.

[0101] The preparation method of compound 10 refers to Example 1, and the o-methylbenzonitrile added in step (1) is replaced by 2-methoxybenzonitrile to obtain compound 10.

[0102] The product was a white solid with a yield of 67% and an mp of 138.2-140.1°C. 1 H NMR (400 MHz, CDCl3) δ 10.44 (s, 1H), 8.41 (dd, J = 7.6, 2.0 Hz, 1H), 8.31 (d, J = 4.0 Hz, 2H), 7.73 (d, J = 8.0 Hz, 2H), 7.49 – 7.41 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.13 (t, J = 7.6Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 4.05 (s, 3H), 2.39 (s, 3H). 13 C NMR (101 MHz,CDCl3) δ 162.64, 157.46, 156.70, 148.50, 147.46, 140.87, 131.48, 131.04,129.43, 128.33, 127.83, 125.36, 121.43, 121.05, 111.52, 55.63, 21.54. HRMS(ESI) calcd forC 19 H 17 N3O2S[M+H] + : 400.0114, found 352.1113.

[0103] Example 11

[0104] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(3-methoxyphenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0105]

[0106] Compound 11

[0107] In compound 11, R1 is monosubstituted and the substituent is a methoxy group (the position of the substituent is different from that of compound 10), and R2 is monosubstituted and the substituent is a methyl group.

[0108] The preparation method of compound 11 refers to Example 1, and the o-methylbenzonitrile added in step (1) is replaced by 3-methoxybenzonitrile to obtain compound 11.

[0109] The product obtained in this example was a white solid with a yield of 69% and an mp of 117.4-119.9°C. 1 H NMR (400 MHz, DMSO- d 6) δ 11.73 (s, 1H), 8.62 (s, 1H), 8.50 (s, 1H), 7.71 (s, 1H), 7.66 (t, J =6.8 Hz, 3H), 7.48 (t, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.14 (dd, J = 8.4,2.6 Hz, 1H), 3.89(s,3H), 2.36(s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 167.73,160.30, 157.27, 149.84, 149.43,140.54,134.14, 132.07, 130.95, 129.97, 127.66,126.15, 119.61, 116.93, 112.36, 55.94, 21.53. HRMS(ESI) calcd forC 19 H 17 N3O2S[M+H] + : 400.0114, found 352.1114.

[0110] Example 12

[0111] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N' -(4-methylbenzylidene)-2-(2-trifluoromethylphenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0112]

[0113] Compound 12

[0114] In compound 12, R1 is monosubstituted and the substituent is trifluoromethyl, and R2 is monosubstituted and the substituent is methyl.

[0115] The preparation method of compound 12 refers to Example 1, and the o-methylbenzonitrile added in step (1) is replaced by 2-trifluoromethylbenzonitrile to obtain compound 12.

[0116] The product obtained in this example was a white solid with a yield of 65% and an mp of 154.1~155.2℃. 1 H NMR (400 MHz, DMSO- d 6) δ 11.63 (s, 1H), 8.67 (s, 1H), 8.53 (s, 1H), 7.96 (d, J = 7.6 Hz, 1H),7.85 (d, J = 4.4 Hz, 2H), 7.81 (dd, J = 8.0, 4.3 Hz, 1H), 7.61 (d, J = 8.0 Hz, 2H),7.26 (d, J = 7.6 Hz, 2H), 2.34 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 163.83,156.68, 148.95, 148.91, 139.95, 132.65, 132.60, 131.54, 131.20, 130.85,129.37, 127.70, 127.35 (q, J = 30.5 Hz), 127.12, 126.66 (q, J = 5.2 Hz), 122.22(q, J = 274.0 Hz)20.97. HRMS(ESI) calcd forC 19 H 14 F3N3OS[M+H] + : 390.0882, found390.0882.

[0117] Example 13

[0118] In this example, a compound containing a phenylthiazole acylhydrazone structure was prepared, and its name is N'-(4-methylbenzylidene)-2-(2-methyl, 4-fluorophenyl)thiazole-4-acylhydrazone, and its structural formula is as follows:

[0119]

[0120] Compound 13

[0121] In compound 13, R1 is disubstituted and the substituents are F and methyl, and R2 is monosubstituted and the substituent is methyl.

[0122] The preparation method of compound 13 refers to Example 1, and the o-methylbenzonitrile added in step (1) is replaced by 4-fluoro, 2-methylbenzonitrile to obtain compound 13.

[0123] The product obtained in this example was a white solid with a yield of 66% and an mp of 157.4~159.5℃. 1 H NMR (400 MHz, DMSO- d 6) δ 11.61 (s, 1H), 8.60 (s, 1H), 8.54 (s, 1H), 7.93 (dd, J = 8.4, 5.9 Hz,1H), 7.62 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.4 Hz, 3H), 7.18 (td, J = 8.4, 2.8 Hz,1H), 2.59 (s, 3H), 2.33 (s, 3H). 13 C NMR (101 MHz, DMSO- d 6) δ 165.83, 162.60 (d, J = 248.3 Hz), 156.84, 148.91, 148.88, 139.86, 139.40 (d, J = 8.7 Hz), 132.08 (d, J = 9.0 Hz), 131.55, 129.30, 128.44 (d, J = 3.0 Hz), 127.05, 125.93, 117.83 (d, J = 21.6 Hz), 113.16 (d, J = 21.6 Hz), 20.97 (d, J= 1.4 Hz), 20.90. HRMS(ESI)calcd forC 19 H 16 FN3OS[M+H] + : 354.1071, found 354.1071.

[0124] Example 14

[0125] This example compares the effects of the above 13 compounds and commercial fungicides (anthraquinone, thiophanate-methyl and succinimide) on plant pathogenic fungi, as follows:

[0126] Select the rice blast pathogen ( Magnaportheoryzae ), tea anthracnose ( Colletotrichum gloeosporioides ), Bipolaris maydis ( Bipolarism may be )、Sclerotinia sclerotiorum ( Sclerotinia sclerotia ), Verticillium dahliae ( Verticillium dahliae ) as the test strain, and the mycelial growth rate method was used to determine the phytopathic fungicidal activity of the test compounds according to the Agricultural Industry Standard of the People's Republic of China (NY / T 1156.2-2006). The test results are shown in Table 1.

[0127] Table 1 Inhibition rate of compounds 1-13 against five plant pathogenic fungi at a concentration of 25 μg / mL (%)

[0128]

[0129] Note: Each treatment was repeated 3 times (mean ± SD).

[0130] Example 15

[0131] This example compares the effects of the above 13 compounds and a commercial bactericide (thiophanate-methyl) on the activity of plant pathogenic bacteria, as follows:

[0132] Select rice bacterial blight pathogen ( Xanthomonas oryzae) and tomato bacterial wilt pathogen ( Ralstonia nightshade ) as the test strain. The inhibitory activity of the test compounds against plant pathogenic bacteria was determined using the turbidity method for bacterial growth inhibition according to the Agricultural Industry Standard of the People's Republic of China (NY / T 1156.16-2008). The test results are shown in Table 2.

[0133] Table 2 Inhibitory effects of compounds 1-13 on two plant pathogenic bacteria at a concentration of 100 μg / mL (%)

[0134]

[0135] Note: Each treatment was repeated 3 times (mean ± SD).

[0136] The results of Examples 14 and 15 show that the test compounds exhibited significant fungicidal activity against the above-tested plant pathogenic fungi and plant pathogenic bacteria. The test compounds exhibited moderate to strong fungicidal activity against all five plant pathogenic fungi tested, particularly against rice blast and tea anthracnose, with most compounds showing stronger fungicidal effects than the commercial control agents thiabendazole, sinoprolin, and thiophanate-methyl. In addition, strong fungicidal activity was also exhibited against rice bacterial blight and tomato bacterial wilt, with most compounds showing stronger fungicidal effects than the commercial control agent thiabendazole.

[0137] It can be seen that the compound containing a phenylthiazole acylhydrazone structural skeleton designed and prepared by the present invention has a broad-spectrum and highly effective fungicidal activity and has great application potential and value in the field of plant disease prevention and control.

[0138] The above implementation cases are only for illustrating the technical solutions and features of the present invention, and their purpose is to enable people familiar with the technology to implement them better. They cannot be used to limit the scope of protection of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention are within the scope of protection of the present invention. The ones not described in detail are prior art.

Claims

1. Use of a compound containing a phenylthiazole acylhydrazone structure as an agricultural fungicide in plant disease prevention and control, characterized in that: The compound is used as an agricultural fungicide for preventing and controlling agricultural fungal diseases and agricultural bacterial diseases. The structural formula of the compound is shown in formula (I): （Ⅰ） In formula (I), R1 and R2 are each independently unsubstituted, monosubstituted or disubstituted, and their substituents are selected from hydrogen, halogen, C1-C8 straight-chain or branched alkyl, hydroxyl, amino, nitro, mercapto, carboxyl, cyano, aldehyde, C1-C8 alkoxy, C1-C8 straight-chain or branched alkyl substituted by 1-3 halogens, and C1-C8 straight-chain or branched alkoxy substituted by 1-3 halogens.

2. The use according to claim 1, characterized in that The agricultural fungal diseases are selected from rice blast, tea anthracnose, corn leaf spot, rapeseed sclerotinia and cotton verticillium wilt, and the agricultural bacterial diseases are selected from rice bacterial blight and tomato bacterial wilt.

3. The use according to claim 1, characterized in that The dosage form of the agricultural fungicide is selected from emulsifiable concentrate, water emulsion, microemulsion, wettable powder, water dispersible granule and suspension.

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