CN112592321B

CN112592321B - 1,2,3-triazole hydrazide or amide compounds, and preparation method and application thereof

Info

Publication number: CN112592321B
Application number: CN202110059431.5A
Authority: CN
Inventors: 王培义; 丁月; 龙周卿; 张玲; 吉庆田
Original assignee: Guizhou University
Current assignee: Guizhou University
Priority date: 2021-01-15
Filing date: 2021-01-15
Publication date: 2023-05-09
Anticipated expiration: 2041-01-15
Also published as: CN112592321A

Abstract

The invention relates to a 1,2,3-triazole hydrazide or amide compound, a preparation method and application thereof. The compound has a structure shown in a general formula (I):

Description

1,2,3-triazole hydrazide or amide compounds, and preparation method and application thereof

Technical Field

The invention relates to the technical field of pharmaceutical chemistry, in particular to a 1,2,3-triazole hydrazide or amide compound containing a substituted phenyl and a benzylidene structure, and a preparation method and application thereof.

Background

With the increasing population, grain safety is again becoming a rigid requirement. Among the many factors that lead to food shortages, plant microbial diseases lead to dramatic decreases in crop quality and yield per unit. Pathogenic fungi such as Phytocassa, rhizoctonia cerealis, pitaya anthracis, alternaria wheat, etc. are the most damaging plant parasitic organisms and can cause serious diseases on various crops; second are pathogenic bacteria including notorious bacterial blight of rice, citrus canker, and kiwi bacterial ulcers. Chemical pesticides are still the primary aid in controlling plant microbial disease, however, the gradual decrease in efficacy, especially resistance by pathogenic microorganisms, has plagued people and led to an increase in the number of infections. Furthermore, the emergence and propagation of strains of multidrug-resistant microorganisms complicates the situation. Thus, there is an urgent need to develop novel and effective pesticides with unique modes of action to control plant microbial diseases.

Investigation has shown that studies on triazole bactericides and derivatives thereof have been conducted in view of their general purpose triazole moiety functioning as a vital bioactive nucleus. Among these flexible triazoles, 1,2,3-triazole is easily synthesized by Cu (I) -catalyzed click chemistry with Huisgen 1, 3-dipolar cycloaddition, since its derivatives have various pharmacological activities including antibacterial, antifungal, anticancer, antitubercular, and anti-HIV activities. In particular, some 1,2,3-triazole compounds have been used as β -lactamase inhibitors (Tazobactam acid), antibacterial drugs (Cefatrizine), anticancer drugs (carboximidamide), and anticonvulsants (Rufinamide). Notably, the incorporation of 1,2,3-triazole as a promising pharmacophore into the target compound may facilitate the discovery of new bactericides, distinguishing the current structure of SDHIs. Meanwhile, it is expected to find out compounds with higher biological activity, which provides important scientific basis for developing and creating new pesticides.

The study of the biological activity of 1,2,3-triazole and hydrazide or amide compounds has been developed as follows:

in 2018, bi et al [ Bi, f.; ji, s.h.; venter, h.; liu, j.r.; semple, s.j.; ma, s. Substitution of terminal amide with 1H-1,2,3-triazole: identification of unexpected class of potent antibacterial agents.biorg.med.chem. Lett.2018, 28, 884-891.], according to 3-methyl

Oxybenzamide (3-MBA) derivatives have been identified as novel potent antibacterial agents against the bacterial cell division protein FtsZ. As one of the isosteres of the amide groups, 1,2,3-triazole can mimic the topological and electronic characteristics of the amide. A series of 3-MBA analogs containing 1H-1,2,3-triazole are prepared by substitution of terminal amides with triazole alleles, thereby enhancing antibacterial activity. Wherein, the minimum inhibitory concentration of one analogue to bacillus subtilis and staphylococcus aureus is 2 mug/mL, and the analogue also has better inhibitory effect to escherichia coli.

In 2010, sumangla et al [ sumangla, v.; pooJary, B.; chidananda, n.; fernandes, j.; kumari, n.s. synthesis and antimicrobial activity of, 2,3-triazoles containing quinoline mole.arch.pharm.res.2010, 33, 1911-1918 ], a series of new substituted 1,2,3-triazoles were synthesized from 4-azido-2, 8-bistrifluoromethylquinolines and the biological activity of all synthesized compounds on bacteria (e.g., staphylococcus aureus, pseudomonas aeruginosa and klebsiella pneumoniae) and fungi (aspergillus flavus, aspergillus fumigatus, penicillium marneffei and trichomonas gracilis) was evaluated in vitro. The results show that some of the compounds exhibit excellent antimicrobial activity against all microorganisms tested at concentrations of 3.125 and 6.25 μg/mL.

2017, wang et al [, x.; dai, z.c.; chen, y.f.; cao, l.l.; yan, w.; li, S.K.; wang, j.x.zhang, z.g.; ye, Y.H.Synthesis of 1,2,3-triazole hydrazide derivatives exhibiting anti-phytathogenic activity, eur.J.Med.chem.2017, 126, 171-182.]A series of novel hydrazide derivatives of 1,2,3-triazole were designed and synthesized, and antifungal activity against Rhizoctonia solani, sclerotinia sclerotiorum, alternaria wheat and Pyricularia oryzae was studied. The results show that all these target compounds have significant activity. Of these, compound 6ad showed the best antifungal activity, and its EC ₅₀ Values of 0.18, 0.35, 0.37, 2.25mg/mL, respectively, activity comparable to or better than the agent control carbendazim; in vivo experiments also find that 6ad has remarkable control effects on rice sheath blight disease, rape sclerotinia, fusarium and rice blast caused by the plant pathogenic bacteria.

In 2019, nalawade et al [ Nalawade, j.; shinde, a.; chavan, a.; patil, s.; suryovansi, m.; modak, M.; choudhari, p.; bobade, v.d.; mhaske, p.c. synthesis of new thiazolyl-pyrazolyl-1,2,3-triazole derivatives as potential antimicrobial agents, eur.j. Med. Chem.2019, 179, 649-659.], a series of thiazolyl-pyrazolyl-1,2,3-triazole derivatives were synthesized, and the results of the biological activity screening showed that most of the target compounds had better antibacterial activity against gram-negative strains, e.g. escherichia coli and proteus, gram-positive strains, staphylococcus albus; meanwhile, part of the derivatives also show outstanding inhibitory activity on Aspergillus niger at a concentration of 31.5. Mu.g/mL.

In 2018, lal et al [ Lal, K.; yadav, p.; kumar, a.; kumar, a.; paul, A.K. design, synthesis, chemistry, antimicrobial evaluation and molecular modeling studies of some dehydroacetic acid-chalcone-1,2,3-triazo hybrid, biorg. Chem.2018, 77, 236-224 ], designed and synthesized a series of dehydroacetic acid-chalcone-1,2,3-triazole derivatives. The biological activity test results show that part of the compounds show excellent inhibitory activity on the escherichia coli, wherein the MIC value of the compound with the best activity on the escherichia coli is 0.0030 mu M/mL.

Disclosure of Invention

One of the purposes of the present invention is to provide a substituted phenyl, benzyl, 1,2,3-triazole hydrazide or amide compound.

It is another object of the present invention to provide an intermediate compound for preparing the above compound and a method for preparing the same.

It is a further object of the present invention to provide a composition comprising the above compound.

It is a further object of the present invention to provide the use of the above compounds, or of the composition.

It is another object of the present invention to provide a method for controlling agricultural pests using the above-mentioned compound, or the composition.

In order to achieve the above purpose, the present invention adopts the following technical scheme:

a substituted phenyl, benzylidene, 1,2,3-triazole hydrazide or amide compound or a salt or solvate thereof, wherein the compound has a structure shown in a general formula (I):

wherein the method comprises the steps of

R is selected from one or more of hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl;

R ₁ one or more selected from hydrogen, deuterium, optionally substituted or unsubstituted alkyl, optionally substituted or unsubstituted alkenyl, optionally substituted or unsubstituted alkynyl, optionally substituted or unsubstituted alkoxy, optionally substituted or unsubstituted cycloalkyl, optionally substituted or unsubstituted aryl, optionally substituted or unsubstituted heteroaryl;

preferably, R is selected from one or more of hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, substituted or unsubstituted C6-C15 aryl, said substituted referring to being substituted by one or more of C1-C6 alkyl, C1-C6 alkoxy, S, O, amino, hydroxy, halogen, nitro, trifluoromethyl;

R ₁ one or more selected from hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, substituted or unsubstituted C6-C15 aryl, substituted or unsubstituted C6-C10 heteroaryl, said substituted referring to being substituted by one or more of C1-C6 alkyl, C1-C6 alkoxy, amino, hydroxy, halogen, nitro, trifluoromethyl;

preferably, R is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, amino, hydroxy, halogen, nitro, trifluoromethyl, pyridyl, phenyl, chlorophenyl, bromophenyl, fluorophenyl, dichlorophenyl, dibromophenyl, difluorophenyl;

R ₁ selected from the group consisting of

C1-C4 alkyl, trifluoromethyl, pyridyl, phenyl, chlorophenyl, bromophenyl, fluorophenyl, dichlorophenyl, dibromophenyl, difluorophenyl,>

wherein the benzene ring is substituted by one or more R ₂ Substituted, R ₂ Selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, C1-C4 alkoxy, amino, hydroxy, halogen, nitro, trifluoromethyl, trifluoromethoxy, cyano, methylsulfonyl, pyridyl, phenyl.

Most preferably, the compound or salt or solvate thereof is selected from the following specific compounds:

the invention also provides an intermediate compound for preparing the substituted phenyl, the benzylidene, the 1,2,3-triazole hydrazide or the amide compound or the salt or the solvate thereof, which is characterized by comprising the following steps of:

the invention also provides a preparation method of the substituted phenyl, the benzylidene, the 1,2,3-triazole hydrazide or the amide compound or the salt or the solvate thereof, which is characterized by comprising the following steps:

wherein R is ₁ 、R ₂ As described above.

The invention also provides a composition containing the compound or the salt or the solvate thereof, and an agriculturally usable auxiliary or bactericide, insecticide or herbicide; preferably, the formulation of the composition is selected from the group consisting of Emulsifiable Concentrates (EC), powders (DP), wettable Powders (WP), granules (GR), aqueous Solutions (AS), suspensions (SC), ultra low volume sprays (ULV), soluble Powders (SP), microcapsules (MC), smoke agents (FU), aqueous Emulsions (EW), water dispersible granules (WG).

The compound or the salt or the solvate thereof, or the composition can be used for controlling agricultural diseases and insect pests, preferably, the agricultural diseases and insect pests are plant bacterial diseases or fungal diseases; more preferably, the agricultural pest is a plant leaf blight and a plant canker; most preferably, the agricultural pest is rice bacterial leaf blight, cucumber bacterial leaf blight, konjak bacterial leaf blight, citrus canker, grape canker, tomato canker, kiwi fruit canker, apple canker, cucumber gray mold pathogen, pepper fusarium wilt pathogen, rape sclerotinia rot, wheat red mold pathogen, potato late blight pathogen, blueberry root rot pathogen.

The invention also provides a method for controlling agricultural insect pests, which enables the compound or salt or solvate thereof or the composition to act on harmful substances or living environments thereof; preferably, the agricultural pest is a bacterial or fungal plant disease; more preferably, the agricultural pest is rice bacterial leaf blight, tobacco bacterial wilt, cucumber bacterial leaf blight, konjak bacterial leaf blight, citrus canker, grape canker, tomato canker, kiwi fruit canker, apple canker, cucumber gray mold, pepper fusarium wilt, rape sclerotinia rot, wheat red mold, potato late blight, blueberry root rot.

The present invention also provides a method for protecting plants from agricultural pests comprising the step of contacting the plants with said compound or salt or solvate thereof, or said composition.

The term "alkyl" as used herein is intended to include both branched and straight chain saturated hydrocarbon groups having a specified number of carbon atoms. For example "C _1-10 Alkyl "(or alkylene) is intended to mean C1, C2, C3, C4, C5, C6, C7, C8, C9 and C10 alkyl. In addition, e.g. "C _1-6 Alkyl "means an alkyl group having 1 to 6 carbon atoms. Alkyl groups may be unsubstituted or substituted such that one or more of its hydrogen atoms is replaced by another chemical group. Examples of alkyl groups include, but are not limited to, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl) and the like。

"alkenyl" is a hydrocarbon that includes both straight or branched chain structures and has one or more carbon-carbon double bonds that occur at any stable point in the chain. For example "C _2-6 Alkenyl "(or alkenylene) is intended to include C2, C3, C4, C5 and C6 alkenyl groups. Examples of alkenyl groups include, but are not limited to, vinyl, 1-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-methyl-2-propenyl, 4-methyl-3-pentenyl and the like.

"alkynyl" is a hydrocarbon that includes both straight or branched chain structures and has one or more carbon-carbon triple bonds that occur at any stable point in the chain. For example "C _2-6 Alkynyl "(or alkynylene) is intended to include C2, C3, C4, C5, and C6 alkynyl; such as ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like.

The term "substituted" as used herein refers to any one or more hydrogen atoms on a specified atom or group being replaced with a selected specified group, provided that the specified atom's general valency is not exceeded. Substituents are named to the central structure, unless otherwise indicated. For example, it is understood that when (cycloalkyl) alkyl is the possible substituent, the point of attachment of the substituent to the central structure is in the alkyl moiety. As used herein, a ring double bond is a double bond formed between two adjacent ring atoms (e.g., c= C, C =n or n=n). When referring to substitution, particularly polysubstituted, it is meant that a plurality of substituents are substituted at various positions on the indicated group, e.g. dichlorophenyl refers to 1, 2-dichlorophenyl, 1, 3-dichlorophenyl and 1, 4-dichlorophenyl.

Combinations of substituents and or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates. The stable compound or stable structure implies that the compound is sufficiently stable when isolated from the reaction mixture in useful purity, and is formulated to form an effective therapeutic agent. Preferably, the compounds at present do not comprise N-halogen, S (O) ₂ H or S (O) H group.

The term "aryl" refers to a monocyclic or bicyclic aromatic hydrocarbon group having 6 to 12 carbon atoms in the ring portion, such as phenyl and naphthyl, each of which may be substituted.

The term "halogen" or "halogen atom" refers to chlorine, bromine, fluorine and iodine.

The term "haloalkyl" refers to a substituted alkyl group having one or more halogen substituents. For example, "haloalkyl" includes mono-, di-and trifluoromethyl; even though the halo in the haloalkyl is explicitly fluoro, chloro, bromo, iodo, it also refers to substituted alkyl groups having one or more fluoro, chloro, bromo, iodo substituents.

The term "heteroaryl" refers to substituted and unsubstituted aromatic 5-or 6-membered monocyclic groups, 9-or 10-membered bicyclic groups, and 11 to 14-membered tricyclic groups, having at least one heteroatom (O, S or N) in at least one ring, said heteroatom-containing ring preferably having 1,2 or 3 heteroatoms selected from O, S and N. Each ring of the heteroatom-containing heteroaryl group may contain one or two oxygen or sulfur atoms and/or from 1 to 4 nitrogen atoms provided that the total number of heteroatoms in each ring is 4 or less and that each ring has at least one carbon atom. The fused ring completing the bicyclic and tricyclic groups may contain only carbon atoms and may be saturated, partially saturated, or unsaturated. The nitrogen and sulfur atoms may optionally be oxidized and the nitrogen atoms may optionally be quaternized. Bicyclic or tricyclic heteroaryl groups must include at least one wholly aromatic ring and the nitrogen other fused rings may be aromatic or non-aromatic. Heteroaryl groups may be attached at any available nitrogen or carbon atom of any ring. When the valency permits, if the other ring is cycloalkyl or heterocycle, it is additionally optionally substituted with =o (oxygen).

Exemplary monocyclic heteroaryl groups include pyrrolyl, pyrazolyl, pyrazolinyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, furanyl, thienyl, oxadiazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, and the like.

Exemplary bicyclic heteroaryl groups include indolyl, benzothiazolyl, benzodioxolyl, benzoxazolyl, benzothienyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzofuranyl, indolizinyl, benzofuranyl, chromonyl, coumarin, benzofuranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridinyl, fluoropyridyl, dihydroisoindolyl, tetrahydroquinolinyl, and the like.

The compounds of the present invention are understood to include both the free form and salts thereof, unless otherwise indicated. The term "salt" means an acid and/or base salt formed from inorganic and/or organic acids and bases. In addition, the term "salt" may include zwitterionic (inner salts), such as when the compounds of formula I contain basic moieties such as amine or pyridine or imidazole rings, and acidic moieties such as carboxylic acids. Pharmaceutically acceptable (i.e., non-toxic, physiologically acceptable) salts are preferred, such as acceptable metal and amine salts, wherein the cation does not contribute significantly to the toxicity or bioactivity of the salt. However, other salts may be useful, such as by employing isolation or purification steps in the preparation process, and are therefore also included within the scope of the present invention.

Preferably C ₁ -C ₁₀ Alkyl refers to methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and isomers thereof; c (C) ₁ -C ₁₀ Alkoxy refers to methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy, octoxy, nonoxy, decyloxy and isomers thereof; c (C) ₂ -C ₅ Alkenyl refers to ethenyl, propenyl, allyl, butenyl, pentenyl and isomers thereof.

When referring to substituents as alkenyl, alkynyl, alkyl, halogen, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxy, amino, mercapto, phosphino, or when referring to such substituents as in particular to a particular alkenyl, alkynyl, alkyl, halogen, aryl, heteroaryl, alkoxy, cycloalkyl, hydroxy, amino, mercapto, phosphino, one to three of the above substituents are meant. For example methylphenyl refers to one to three methyl-substituted phenyl groups.

By adopting the technical scheme, the invention synthesizes a series of substituted phenyl, benzylidene, 1,2,3-triazole hydrazide or amide compounds based on 1,2,3-triazole hydrazide or amide, and discovers that the compounds have good inhibition effect on pathogenic fungi, and have good inhibition effects on pathogenic fungi [ such as Gibberella zeae (G.z.), rhizoctonia cerealis (Rhizoctonia solani, R.s), botrytis cinerea (Botryosphaeria dothidea, B.d.) ], and provides an important scientific basis for research and development and creation of new pesticides.

Detailed Description

The invention is further illustrated by the following examples. It should be understood that the methods described in the examples of the present invention are only for illustrating the present invention, and not for limiting the present invention, and that simple modifications to the preparation methods of the present invention under the concept of the present invention are within the scope of the present invention as claimed. All the starting materials and solvents used in the examples are commercially available products.

Example 1: preparation of intermediate 2 (methyl 4- (azidomethyl) benzoate)

Raw material 4-bromomethylbenzoate (5.00 g,21.83 mmol) and sodium azide (7.10 g,0.11 mol) were added to a 100mL reaction flask, 14mL of N, N-Dimethylformamide (DMF) was added, the reaction was stopped after heating to 60℃for 4 hours, extraction was performed with ethyl acetate, saturated ammonium chloride was washed three to four times, dried over anhydrous sodium sulfate, and desolventized to give 4.12g of colorless oil in 98.80% yield.

Example 2: preparation of intermediate 3 (methyl 4- ((4- (2-chlorophenyl) -1H-1,2, 3-triazol-1-yl) methyl) benzoate)

Intermediate 2 (4.0 g,20.92 mmol) and 1-chloro-2-ethynylbenzene (2.60 g,19.02 mmol) were dissolved in 10mL of THF, then 10mL of water was added to the system, anhydrous copper sulfate (0.48 g,1.90 mmol) and sodium ascorbate (0.75 g,3.80 mmol) were dissolved in 8mL of water and then added dropwise to the above system, the reaction was stopped after 14 hours at normal temperature, desolventized, dissolved with water, extracted with dichloromethane, dried over anhydrous sodium sulfate, desolventized, and separated by column chromatography to give 6.24g of a white solid with a yield of 99.39%. The nuclear magnetic data are as follows: ¹ H NMR(50 0MHz，CDCl ₃ )δ8.23(dd，J＝7.9，1.7Hz，1H，2-Cl-phenyl-H)，8.15(s，1H，t riazole-H)，8.03-8.00(m，2H，benzene-H)，7.40(dd，J＝8.0，1.3Hz，1H，2-Cl-ph enyl-H)，7.36-7.33(m，2H，benzene-H)，7.33-7.31(m，1H，2-Cl-phenyl-H)，7.24 (ddd，J＝9.1，6.6，1.3Hz，1H，2-Cl-phenyl-H)，5.65(s，2H，CH ₂ )，3.89(s，3H， CH ₃ )； ¹³ C NMR(126MHz，CDCl ₃ )δ166.5，144.6，139.6，131.2，130.6，130.4，1 30.3，129.8，129.2，129.1，127.8，127.3，123.4，53.8，52.4.

example 3: preparation of intermediate 4 (4- ((4- (2-chlorophenyl) -1H-1,2, 3-triazol-1-yl) methyl) benzoic acid)

Intermediate 3 (4.30 g,13.12 mmol) was dissolved in 20mL tetrahydrofuran, then 20mL water in which KOH (1.10 g,19.68 mmol) was dissolved was added to the system, the reaction was stopped after heating to 55℃for 3 hours, the reaction was desolventized, the pH was adjusted to 3-4 with dilute hydrochloric acid, a large amount of solids was precipitated, and the solution was suction-filtered to give 3.85g of a white solid with a yield of 93.3%. The nuclear magnetic data are as follows: ¹ H NMR(400MHz，DMS0-d6)δ13.04(s，1H，-COOH)， 8.82(s，1H，triazole-H)，8.09(dd，J＝7.8，1.8Hz，1H，2-Cl-phenyl-H)，7.96(d， J＝8.3Hz，2H，benzene-H)，7.56(dd，J＝7.9，1.3Hz，1H，2-Cl-phenyl-H)，7.4 8-7.44(m，2H，benzene-H)，7.44(d，J＝2.5Hz，1H，2-Cl-phenyl-H)，7.41-7.35 (m，1H，2-Cl-phenyl-H)，5.80(s，2H，CH ₂ )； ¹³ C NMR(101MHz，DMSO-d ₆ )δ1 67.4，143.3，141.3，131.0，130.8，130.7，130.3，130.0，129.5，128.4，128.0，125.2， 53.0.

example 4: preparation of the target Compound (4- ((4- (2-chlorophenyl) -1H-1,2, 3-triazol-1-yl) methyl) -N' -phenylbenzoyl hydrazine)

In a pressure-resistant bottle, intermediate 3 (0.2 g,0.64 mmol), EDCI (0.24 g,1.27 mmol) and HOBT (0.09 g,0.64 mmol) were added, and after 8mL of dichloromethane was added, triethylamine (0.13 g,1.27 mmol) was added, and after 10 minutes of reaction at normal temperature, phenylhydrazine hydrochloride (0.11 g,0.76 mmol) was added, the reaction was stopped at a spot and plate, desolventized, extracted with ethyl acetate after adding water, dried over anhydrous sodium sulfate, desolventized, and separated by column chromatography to give yellow solid 0.22g, yield 86.43%.

Other target compounds were synthesized using the corresponding starting materials or substituents, with reference to the procedure of the examples described above.

The structure and nuclear magnetic resonance hydrogen spectrum and carbon spectrum data of the synthesized substituted phenyl, benzylidene, 1,2,3-triazole hydrazide or amide partial compounds are shown in table 1, and the physical and chemical properties are shown in table 2.

TABLE 1 Nuclear magnetic resonance Hydrogen Spectroscopy and carbon Spectroscopy data for the compounds of the present application

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TABLE 2 physicochemical Properties of the Compounds of the present application

Pharmacological example 1:

EC ₅₀ (median effective concentration) is an important index for evaluating sensitivity of plant pathogenic bacteria to compoundsThe target is also an important parameter for setting the concentration of the compound when researching the action mechanism of the target compound. In the concentration gradient experiment, proper 5 concentrations are set by adopting a double dilution method, and finally the inhibition rate of the medicament to plant pathogenic bacteria and the medicament concentration are converted into logarithmic values, and the virulence curve is obtained by SPSS software regression analysis, so that EC is calculated ₅₀ 。

Testing the effective medium concentration EC of the target compound against plant pathogenic bacteria by using growth rate method ₅₀ The test subjects were gibberella wheat (G.z), botrytis cinerea (b.d), and banded sclerotial blight of rice (R.s). DMSO was dissolved in the medium as a blank. Weighing a compound to be measured by a ten-thousandth balance, adding 1mL of DMSO to dissolve the compound, transferring to a 15mL sterilized centrifuge tube in a sterile operation table, adding 9mL of Tween-water (Tween-20) to a volume of 10mL, pouring into a melted culture medium, uniformly mixing, and evenly split charging into 9 culture dishes for later use; in a sterile operation table, a puncher (5 mm) is burnt and sterilized, bacterial colonies are made into bacterial cakes, the bacterial cakes are connected to the center of a culture medium by a bacterial connection ring, the bacterial cakes are cultured for about 5 days at the temperature of 25-28 ℃, the bacterial colonies of a blank control are measured for 2 times by a straight ruler according to a crisscross method when the bacterial colonies grow to about 6cm, and the average value is taken as the diameter of the bacterial colonies. The hypha growth inhibition rate of each concentration is calculated according to a calculation formula, and a linear regression equation is made according to the concentration and the corresponding inhibition rate, so that EC is obtained ₅₀ Values, fluopyram, boscalid were used as a drug control to participate in the test together.

Inhibition (%) = (N1-N2)/(N1-0.5) ×100

0.5-diameter/cm of parent fungus cake;

n1-control colony diameter, i.e., colony diameter of control group/cm;

n2-diameter of treated colonies, i.e., diameter of colonies treated with target compound/cm:

the present invention is described with the aid of examples, but the contents of examples are not limited thereto, and the experimental results of the target compounds are shown in table 3.

TABLE 3 EC of the compounds of the present application against phytopathogenic fungi ₅₀

As can be seen from table 3, the target compounds generally exhibit good inhibitory activity against phytopathogenic fungi in an ex vivo assay. Wherein compounds 5, 8, 10 have EC against Puccinia ₅₀ The value was lower than that of the reference azoxystrobin (EC ₅₀ =2.30 μg/mL). EC of Compound 5 against gibberella wheat ₅₀ The value is lower than 1 mug/mL, and the activity of most compounds is better than that of fluopyram, so that the fluopyram can be used for preparing pesticides for resisting plant pathogenic fungi.

Pharmacological example 2:

EC ₅₀ (median effective concentration) is an important index for evaluating the sensitivity of plant pathogenic bacteria to a compound, and is also an important parameter for setting the concentration of the compound when researching the action mechanism of the target compound. In the concentration gradient experiment, proper 5 concentrations are set by adopting a double dilution method, and finally the inhibition rate of the medicament to plant pathogenic bacteria and the medicament concentration are converted into logarithmic values, and the virulence curve is obtained by SPSS software regression analysis, so that EC is calculated ₅₀ 。

Testing the effective medium concentration EC of the target compound to plant pathogenic bacteria by using turbidity method ₅₀ The test subjects were rice bacterial leaf blight bacteria (Xoo), citrus canker bacteria (Xac) and kiwi fruit canker bacteria (Psa). DMSO was dissolved in the medium as a blank. Putting rice bacterial leaf blight bacteria (rice bacterial leaf blight pathogenic bacteria are in an M210 solid culture medium) into an NB culture medium, and carrying out shake culture in a constant-temperature shaking table at 28 ℃ and 180rpm until the bacterial leaf blight bacteria are in a logarithmic growth phase for later use; the citrus canker fungus (on M210 solid medium) is placed in NB medium and shake-cultured in a thermostatic shaker at 28℃and 180rpm until logarithmic growth phase is ready for use. The kiwi fruit canker (on M210 solid medium) is put into NB medium and is shake-cultured in a constant temperature shaker at 28 ℃ and 180rpm until logarithmic phase is ready for use. Configuring the medicament (compound) not to be5mL of toxic NB liquid culture medium with the same concentration (for example: 100, 50, 25, 12.5,6.25 mug/mL) is added into a test tube, 40 mu L of NB liquid culture medium containing phytopathogenic bacteria is respectively added, and the culture is carried out by shaking in a constant-temperature shaking table at 28-30 ℃ and 180rpm, so that the rice bacterial leaf blight pathogen is cultured for 36h, the citrus canker is cultured for 48h and the kiwi fruit canker is cultured for 28h. Measuring OD of bacterial solutions with various concentrations on a spectrophotometer ₅₉₅ Values, and additionally determining the OD of corresponding concentrations of toxic sterile NB liquid medium ₅₉₅ Values.

Corrected OD = bacteria-containing medium OD-sterile medium OD

Inhibition ratio = [ (corrected control culture medium bacterial liquid OD value-corrected toxic culture medium OD value)/corrected control culture medium bacterial liquid OD value ] ×100

The present invention is described with the aid of examples, but the contents of examples are not limited thereto, and the experimental results of the target compounds are shown in table 4.

TABLE 4 EC of the compounds of the present application against phytopathogenic bacteria ₅₀

As can be seen from Table 4, in the in vitro test, the two target compounds showed good inhibitory activity against plant pathogenic bacteria (such as Rhizoctonia solani and Rhizoctonia cerealis). Compound 18 shows good inhibitory activity against bacterial leaf blight of rice (Xanthomonas oryzae pv. Oryzae, xoo), its EC ₅₀ 28 μg/mL; compound 19 exhibits excellent inhibitory activity against Leuconostoc citruses (Xanthomonas axonopodis pv. Citri, xac), EC thereof ₅₀ 17.9 μg/mL; can be used for preparing pesticides against plant pathogenic bacteria.

Claims

1. A compound, characterized by being selected from the group consisting of:

2. a composition characterized by: comprising a compound according to claim 1, together with agriculturally acceptable adjuvants.

3. Use of a compound according to claim 1 or a composition according to claim 2 for controlling agricultural pests, which are fusarium graminearum, rhizoctonia solani, bacterial blight of rice, and citrus canker.

4. A method for controlling agricultural plant diseases and insect pests, which is characterized by comprising the following steps: allowing the compound according to claim 1, or the composition according to claim 2 to act on a pest or its living environment, wherein the pest is gibberella gracilis, chaetomium viticola, rhizoctonia solani, or Citrus canker.