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CN-121991036-A - Triazolyl isoindolinone compound and preparation method and application thereof

CN121991036ACN 121991036 ACN121991036 ACN 121991036ACN-121991036-A

Abstract

The invention belongs to the field of agricultural science, and discloses a triazolyl isoindolinone compound I, which is obtained by constructing an amide structure by connecting triazole rings containing substituent groups through amino acid based on an isoindolinone skeleton. The compound has the advantages of simple structure, mild synthesis reaction condition, simple operation, high yield and good bactericidal activity, and can be used for developing agricultural bactericides.

Inventors

  • HUANG QINGCHUN
  • WANG HONGYE
  • WANG CHENHUI
  • YANG ZHENREN
  • SUN YUEWEI
  • XIAO CIYING

Assignees

  • 华东理工大学

Dates

Publication Date
20260508
Application Date
20260304

Claims (7)

  1. 1. A triazolyl isoindolinone compound comprising a compound having the structure of formula I: I Wherein: R 1 and R 2 are any one of halogen, nitro, amino, cyano, methyl, ester group or sulfhydryl; r 3 is any one of hydrogen, isopropyl, phenyl, benzyl, substituted phenyl, nitrogen-containing heterocycle or substituted nitrogen-containing heterocycle; r 4 is any one of hydrogen, halogen, nitro, amino, alkyl and aralkyl; l is any one of alkyl groups containing 0-4 carbon atoms. .
  2. 2. The method for preparing the triazolyl isoindolinone compound according to claim 1, which is characterized by comprising the following steps: 1) Dissolving a compound II with amino and carboxyl functional groups and a phthalic anhydride compound III in an organic solvent A and fully reflecting the compound II and the phthalic anhydride compound III, and separating and purifying the fully reacted solution by using an eluent to obtain an intermediate formula IV; 2) Dissolving an intermediate formula IV and a substituted triazole compound V in an organic solvent B, adding alkali and a condensing agent, stirring for 8-16 hours at room temperature, washing, drying, extracting by an organic solvent C, purifying by column chromatography and the like after the reaction is completed, and obtaining a triazolyl isoindolinone compound;
  3. 3. wherein the organic solvent A is glacial acetic acid; The organic solvent B is selected from any one of dichloromethane, 1, 2-dichloroethane, diethyl ether, tetrahydrofuran, acetonitrile and toluene; the organic solvent C is selected from any one of dichloromethane, ethyl acetate, diethyl ether, cyclohexane and n-hexane; Wherein R 1 、R 2 、R 3 、R 4 , L are as defined in claim 1.
  4. 4. The method for preparing the triazolyl isoindolinone compound according to claim 2, characterized in that, The compound II is selected from any one of 4-nitrophthalic anhydride, 4-bromophthalic anhydride, 4-chlorophthalic anhydride, 3-bromophthalic anhydride and 3-chlorophthalic anhydride; The compound III is selected from any one of L-alanine, 2-amino-2-phenylacetic acid, DL-2-aminoisovaleric acid, glycine, beta-alanine and 3-amino-3- (4-chlorophenyl) propionic acid; The compound V is selected from any one of 5-amino-1, 2, 4-triazole-3-carboxylic acid methyl ester, 3-nitro-1, 2, 4-triazole, 3-cyano-1, 2, 4-triazole, -1,2, 4-triazole-3-carboxylic acid methyl ester, 3, 5-dibromo-1, 2, 4-triazole, 3-bromo-1, 2, 4-triazole, 5-chloro-1, 2, 4-triazole, 3, 5-dimethyl-1, 2, 4-triazole, 3-methyl-1, 2, 4-triazole, 3, 5-diamino-1, 2, 4-triazole, 3-amino-1, 2, 4-triazole and 3-mercapto-1, 2, 4-triazole; the base is selected from any one of triethylamine, N-ethyldiisopropylamine, potassium carbonate, cesium fluoride, 4-dimethylaminopyridine, 1, 8-diazabicyclo [5.4.0] undec-7-ene and 1, 5-diazabicyclo [4.3.0] non-5-ene; The condensing agent is selected from any one of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride, N, N ' -carbonyldiimidazole, 2- (7-azabenzotriazol) -N, N, N ', N ' -tetramethyl urea hexafluorophosphate, 1-hydroxybenzotriazole and N, N, N ', N ' -tetramethyl chloroformyl amidine hexafluorophosphate; The developing agent used in the column chromatography is selected from any two of methanol, ethyl acetate, methylene dichloride and n-hexane, wherein the volume ratio of n-hexane to ethyl acetate is (1-7) to 1, or the volume ratio of methylene dichloride to methanol is (10-50) to 1.
  5. 5. The preparation method of the triazolyl isoindolinone compound, which is disclosed in claim 2, is characterized in that in the step 1), the molar ratio of the compound II to the compound III is 1:1-2, and the millimole volume ratio of the compound II to the organic solvent A is 1:1-10 mmol/mL.
  6. 6. The preparation method of the triazolyl isoindolinone compound is characterized in that in the step 2), the molar ratio of the compound IV to alkali is 1:1-4, the molar ratio of the compound IV to a condensing agent is 1:1-2, the molar ratio of the compound IV to the compound V is 1:1-2, and the millimole volume ratio of the compound IV to the organic solvent B is 1:5-10 mmol/mL.
  7. 7. The application of the triazolyl isoindolinone compound in the development of bactericides, which is characterized by having good bactericidal activity on alternaria alternate, rice blast, sclerotinia sclerotiorum, sheath blight of rice, cucumber fusarium wilt, botrytis cinerea, anthracnose of grape, gibberella zeae or alternaria mali.

Description

Triazolyl isoindolinone compound and preparation method and application thereof Technical Field The invention belongs to the field of agricultural science, and relates to an active compound based on isoindolinone group, substituted triazolyl, amide group and the like, and a preparation method and application thereof. Background Plant diseases caused by various plant pathogenic fungi constitute a serious threat to global agricultural production and grain safety. The increase in disease outbreak frequency not only causes crop losses throughout the year, but also is a critical threat to the initiation of large-scale crop epidemics. It is estimated that five key crops, wheat, rice, corn, potato and soybean, can cause up to 60% of the global grain supply to be impacted if they encounter severe fungal epidemics. The isoindoline skeleton structure compound is widely applied to the related fields of materials, medicines and the like, and particularly in the medicine field, a plurality of isoindolinone structure-containing compounds show remarkable biological activities such as anticancer, anti-inflammatory, antirheumatic, antibacterial and the like. The compounds can damage cell walls and cell membrane structures of bacteria or fungi or interfere metabolic processes of the bacteria or fungi, so that the compounds can play a role in inhibiting the bacteria or fungi. In the agricultural field, the compounds are often developed as pesticides and herbicides. Triazole compounds have become indispensable dominant structures in modern pharmaceutical chemistry due to their unique chemical structures and diverse biological activities. Triazole compounds generally have antimalarial, antimuremic, antiviral, anticonvulsant, antioxidant and antifungal activities and are used in a number of critical therapeutic areas. Triazole bactericides are an important systemic bactericide, and the action mechanism of the triazole bactericides is to inhibit biosynthesis of pathogenic fungus ergosterol efficiently and specifically. The target is lanosterol 14 alpha-demethylase (CYP 51), which is a cytochrome P450 monooxygenase superfamily member and catalyzes the demethylation step which is indispensable in the ergosterol synthesis pathway. The amide structure is also a very important functional group, and many antibacterial and anticancer drugs contain the amide structure. Part of the bactericide containing the amide structure can interact with specific components on the cell membrane of the pathogenic bacteria to destroy the integrity and permeability of the cell membrane, so that the cell death is caused, and the bactericide can be combined with key enzymes in the pathogenic bacteria to inhibit the activity of the bactericide. The invention discloses a molecular design strategy based on active substructure splicing, which introduces an isoindolinone skeleton and constructs an amide structure by connecting triazole rings containing substituent groups through amino acid. By adopting an economic and efficient method, the triazolyl isoindolinone compounds with novel structures are synthesized, have good bactericidal activity and can be used for developing agricultural bactericides. . Disclosure of Invention The invention provides a synthetic method of isoindolinone compounds containing a substituted triazole structure, which has a novel structure. The compound has the advantages of simple structure, mild synthesis reaction condition, simple and convenient operation and high yield. Still another object of the present invention is to splice isoindolinone and substituted triazole groups through amide structures of amino acids, and the obtained triazolyl isoindolinone compound can act on multiple targets in pathogenic bacteria simultaneously, thereby reducing the risk of pathogenic bacteria developing drug resistance. In order to achieve the above purpose, the technical scheme adopted by the invention comprises the following steps: The structural general formula of the triazolyl isoindolinone compounds is as follows: I Wherein: R 1 and R 2 are any one of halogen, nitro, amino , cyano, methyl, ester or sulfhydryl; r 3 is any one of hydrogen, isopropyl, phenyl, benzyl, substituted phenyl, nitrogen-containing heterocycle or substituted nitrogen-containing heterocycle; r 4 is any one of hydrogen, halogen, nitro, amino, alkyl and aralkyl; L is any one of C 0-4 alkyl. The invention also provides a preparation method of the triazolyl isoindolinone compound, which comprises the following steps: 1) Dissolving a compound II with amino and carboxyl functional groups and a phthalic anhydride compound III in an organic solvent A, fully reacting, and separating and purifying the fully reacted solution by using an eluent to obtain an intermediate formula IV; 2) Dissolving an intermediate formula IV and a substituted triazole compound V in an organic solvent B, adding alkali and a condensing agent, stirring for 8-16 hours at room temperature, and after the reacti