阅读说明：本技术 一种n-取代苯甲酰腙类化合物及其制备方法与应用 (N-substituted benzoyl hydrazone compound and preparation method and application thereof ) 是由 朱翠萍 于 2020-07-28 设计创作，主要内容包括：本发明提供一种N-取代苯甲酰腙类化合物及其制备方法,该类化合物是由酰腙化合物与二芳基丙烯醇在氧化剂的作用下反应制得的,反应氧化剂为二叔丁基过氧化物,溶剂均为无水1、4-二氧六环,该反应条件简单,有较好的底物普适性,产率高；本发明制备的N-取代苯甲酰腙类化合物具有良好的生物活性,对麦蚜、棉铃虫、红蜘蛛、白粉虱具有优良的杀虫活性,对人体正常细胞低毒,且酰腙基团容易降解,残留时间短,代谢产物低毒或无毒,危害较小,可应用于新农药的制备中。(The invention provides an N-substituted benzoyl hydrazone compound and a preparation method thereof, wherein the compound is prepared by reacting an acylhydrazone compound with diaryl allyl alcohol under the action of an oxidant, the reaction oxidant is di-tert-butyl peroxide, and solvents are anhydrous 1 and 4-dioxane; the N-substituted benzoyl hydrazone compound prepared by the invention has good biological activity, has excellent insecticidal activity on wheat aphids, cotton bollworms, red spiders and trialeurodes vaporariorum, is low in toxicity on normal cells of a human body, is easy to degrade an acylhydrazone group, is short in residual time, low in toxicity or non-toxicity of metabolites, small in harm and capable of being applied to preparation of new pesticides.)

1. An N-substituted benzoyl hydrazone compound, which is characterized in that the structural general formula of the N-substituted benzoyl hydrazone compound is as follows:

wherein R is¹＝H、4-F、4-Cl、4-Br、4-Me、4-OMe、3-CF₃、3,4-2Me；R²＝H、4-F、4-Cl、4-Br、4-Me、4-OMe、3-CF₃；R³＝4-Me、4-OMe、4-Cl、2-OH；R⁴＝4-Me、4-OMe、4-tBu、4-N(CH₃)₂4-F, 4-Cl, 2-OMe and 2-OH; or ArR⁴Furan, thiophene, pyridine, naphthalene, indole.

2. The N-substituted benzoylhydrazone compound of claim 1, comprising the product obtained by the following steps:

the benzoyl hydrazine compound reacts with benzaldehyde to prepare an acylhydrazone compound, and then the acylhydrazone compound reacts with diaryl propylene alcohol under the action of an oxidant to generate the N-substituted benzoyl hydrazone compound.

3. The N-substituted benzoylhydrazone compound of claim 1 or 2, wherein the diarylallyl alcohol is 1, 1-diphenylpropenol, 1, 1-bis (4-fluorophenyl) -propenol, 1, 1-bis (4-chlorophenyl) -propenol, 1, 1-bis (4-bromophenyl) -propenol, 1, 1-bis (4-methylphenyl) -propenol, 1, 1-bis (4-methoxyphenyl) -propenol, 1, 1-bis (3-trifluoromethylphenyl) -propenol, 1-phenyl-1- (4-fluorophenyl) -propenol, 1-phenyl-1- (4-chlorophenyl) -propenol, 1-phenyl-1- (3, 4-dimethylphenyl) -propenol.

4. The N-substituted benzoylhydrazone compound of claims 1 to 2, wherein the resulting acylhydrazone compound is N ' -benzylidene-benzohydrazide, N ' -benzylidene-4-methylbenzohydrazide, N ' -benzylidene-4-methoxybenzohydrazide, N ' -benzylidene-4-chlorobenzohydrazide, N ' -benzylidene-2-hydroxybenzohydrazide, N ' - (4-methylbenzylidene) benzohydrazide, N ' - (2-methoxybenzylidene) benzohydrazide, N ' - (4-tert-butylbenzylidene) benzohydrazide, N ' - (4- (dimethylamino) benzylidene) benzohydrazide, n ' - (4-fluorobenzylidene) benzohydrazide, N ' - (4-chlorobenzylidene) benzohydrazide, N ' - (2-hydroxybenzylidene) benzohydrazide, N ' - (furan-2-methylene) benzohydrazide, N ' - (thiophene-2-methylene) benzohydrazide, N ' - (naphthalene-1-methylene) benzohydrazide, N ' - (1H-indole-3-methylene) benzohydrazide.

5. A method for preparing N-substituted benzoyl hydrazone compounds according to claims 1 to 4, comprising the following general reaction formula and reaction steps:

adding a diaryl propylene alcohol compound, an acylhydrazone compound and an oxidant into a reaction tube, adding a solvent under the protection of inert gas, and then heating and reacting at 100 ℃ for 8 hours to obtain a reaction mixed solution;

and secondly, separating and purifying the reaction mixed liquid obtained in the step one to obtain the N-substituted benzoyl hydrazone compound.

6. The method according to claim 5, wherein the molar mass ratio of the diarylpropenol compound to the acylhydrazone compound to the oxidizing agent is 1:1.1-1.3: 1.2-1.5.

7. The method for preparing N-substituted benzoylhydrazone compound according to claim 5, wherein the solvent is anhydrous 1, 4-dioxane, and the oxidizing agent is di-tert-butyl peroxide.

8. The method for preparing an N-substituted benzoylhydrazone compound according to claim 5, wherein the separation and purification in step two is specifically a column chromatography, and the developing solvent used is ethyl acetate: the volume ratio of the petroleum ether is 1:6-1: 8.

9. The N-substituted benzoyl hydrazone compound is applied to preparation of pesticides for inhibiting wheat aphids, cotton bollworms, red spiders and trialeurodes vaporariorum.

Technical Field

The invention belongs to the technical field of pesticides, and particularly relates to an N-substituted benzoyl hydrazone compound and a preparation method and application thereof.

Background

The benzoyl hydrazine can be used for the production of pesticides, the production of dyes, spices and the like, is also an important intermediate for organic synthesis, and is mainly used for medical intermediates, organic synthesis and organic solvents. The pesticide has a great effect on the development of agriculture, and along with the development of agriculture, the pesticide is used in a large amount, and the production and income increase brings serious environmental and social problems, such as water resource pollution, air pollution, extinction of biological populations, increase of human diseases and the like, so that along with the further enhancement of consciousness of human beings on environmental protection, the concept of people on the pesticide is changed, namely the safety of the pesticide on human beings, environment and non-target organisms is emphasized while the high biological activity is emphasized.

Hydrazide insect growth regulators are high-efficiency, strong-selectivity and environment-friendly insect growth regulators developed successively in recent years, and kill pests by inducing insects to molt in advance but preventing the molting process from being completely carried out. And compared with acylhydrazone pesticide precursor hydrazide compound, -NH₂The base disappears, the toxicity is small, and the low toxicity and high efficiency required by modern pesticides are met.

The acylhydrazone compound molecules contain oxygen atoms and nitrogen atoms at the same time, so that the acylhydrazone compound molecules can participate in the formation of hydrogen bonds in organisms, increase the affinity with receptors and further influence the normal biochemical reaction process in the organisms. The metabolic products of the acylhydrazone groups are low-toxic or non-toxic and less harmful, and the acylhydrazone groups are easy to degrade and have short residual time, so that the method for improving the pesticide, reducing the toxicity and improving the selectivity by introducing the hydrazone groups is a new, more convenient and safer method.

Disclosure of Invention

The invention aims to provide an N-substituted benzoyl hydrazone compound, a preparation method thereof and application thereof in pest inhibition.

The N-substituted benzoyl hydrazone compound has the following structural general formula:

wherein R is¹＝H、4-F、4-Cl、4-Br、4-Me、4-OMe、3-CF₃、3,4-2Me；R²＝H、4-F、4-Cl、4-Br、4-Me、4-OMe、3-CF₃；R³＝4-Me、4-OMe、4-Cl、2-OH；R⁴＝4-Me、4-OMe、4-tBu、4-N(CH₃)₂4-F, 4-Cl, 2-OMe and 2-OH; or ArR⁴Furan, thiophene, pyridine, naphthalene, indole.

The N-substituted benzoyl hydrazone compound can be prepared into a product by the following method:

the benzoyl hydrazine compound reacts with benzaldehyde to prepare an acylhydrazone compound, and then the acylhydrazone compound reacts with diaryl propylene alcohol under the action of an oxidant to generate the N-substituted benzoyl hydrazone compound.

Preferably, the diarylallyl alcohol is 1, 1-diphenylpropenol, 1, 1-bis (4-fluorophenyl) -propenol, 1, 1-bis (4-chlorophenyl) -propenol, 1, 1-bis (4-bromophenyl) -propenol, 1, 1-bis (4-methylphenyl) -propenol, 1, 1-bis (4-methoxyphenyl) -propenol, 1, 1-bis (3-trifluoromethylphenyl) -propenol, 1-phenyl-1- (4-fluorophenyl) -propenol, 1-phenyl-1- (4-chlorophenyl) -propenol, 1-phenyl-1- (3, 4-dimethylphenyl) -propenol;

preferably, the prepared acylhydrazone compound is N '-benzylidene-benzohydrazide, N' -benzylidene-4-methylbenzhydrazide, N '-benzylidene-4-methoxybenzenehydrazide, N' -benzylidene-4-chlorobenzenehydrazide, N '-benzylidene-2-hydroxybenzenehydrazide, N' - (4-methylbenzylidene) benzohydrazide, N '- (2-methoxybenzylidene) benzohydrazide, N' - (4-tert-butylbenzylylidene) benzohydrazide, N '- (4- (dimethylamino) benzylidene) benzohydrazide, N' - (4-fluorobenzylidene) benzohydrazide, n '- (4-chlorobenzylidene) benzohydrazide, N' - (2-hydroxybenzylidene) benzohydrazide, N '- (furan-2-methylene) benzohydrazide, N' - (thiophene-2-methylene) benzohydrazide, N '- (naphthalene-1-methylene) benzohydrazide, N' - (1H-indole-3-methylene) benzohydrazide.

The preparation method of the N-substituted benzoyl hydrazone compound comprises the following steps:

adding a diaryl propylene alcohol compound, an acylhydrazone compound and an oxidant into a reaction tube, adding a solvent under the protection of inert gas, and then heating and reacting at 100 ℃ for 8 hours to obtain a reaction mixed solution;

and secondly, separating and purifying the reaction mixed liquid obtained in the step one to obtain the N-substituted benzoyl hydrazone compound.

Preferably, the molar mass ratio of the diaryl propylene alcohol compound to the acylhydrazone compound to the oxidant is 1:1.1-1.3: 1.2-1.5;

preferably, the solvents are all anhydrous 1, 4-dioxane;

preferably, the oxidizing agent is di-tert-butyl peroxide;

preferably, the separation and purification in the second step is specifically a column chromatography purification method, and the developing agent used is ethyl acetate: the volume ratio of petroleum ether is 1:6-1: 8;

the general formula of the synthetic reaction of the N-substituted benzoyl hydrazone compound is as follows:

the N-substituted benzoyl hydrazone compound is an acylhydrazone compound prepared from a benzoyl hydrazine compound and benzaldehyde, wherein the acylhydrazone compound generates a nitrogen center free radical of acylhydrazone under the action of an oxidant, the free radical attacks a double bond of diaryl propylene alcohol to obtain a carbon center free radical intermediate, and the intermediate is oxidized and deprotonated after intramolecular cyclization and aryl migration to obtain a target product.

The N-substituted benzoyl hydrazone compound has good insecticidal activity on wheat aphids, cotton bollworms, red spiders and trialeurodes vaporariorum, and can be applied to preparation of pesticides.

Compared with the prior art, the invention has the following beneficial effects:

1. the N-substituted benzoyl hydrazone compound prepared by the invention has good biological activity, has excellent insecticidal activity on wheat aphids, cotton bollworms, red spiders and trialeurodes vaporariorum, and has low toxicity on normal cells of a human body.

2. The N-substituted benzoyl hydrazone compound provided by the invention is simple in preparation method, good in substrate universality, and good in application prospect, and the gram-level reaction yield reaches 88%.

Drawings

FIG. 1 shows the antiproliferative activity of N-substituted benzoylhydrazones of the present invention on HEK293 cells.

Detailed Description

The following detailed description of the embodiments of the present invention is provided in connection with the accompanying drawings for the purpose of better understanding and enabling those skilled in the art to practice the invention, and the embodiments are not intended to limit the invention.

The invention relates to an N-substituted benzoyl hydrazone compound, which has the structural formula:

^aratio of the Compound to its isomer

References to the preparation of acylhydrazone compounds as starting materials (Vantomme G, Jiang S M, Lehn jm. addition in structural Dynamic precursors and Networks, swithching between organic precursors and Processes [ J ]. j.am. chem. soc., 136(26): 9509-: weighing a certain amount of benzoyl hydrazine, dissolving in ethanol, adding benzaldehyde, heating for refluxing, stirring overnight, detecting by TLC (thin layer chromatography) for complete reaction, cooling the reaction liquid to room temperature, separating out solids, filtering, separating, recrystallizing the solids with ethanol, and washing with diethyl ether to obtain the pure benzoyl hydrazine compound.