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CN-122010824-A - Amide derivative containing trifluoromethyl pyridine and synthetic method and application thereof

CN122010824ACN 122010824 ACN122010824 ACN 122010824ACN-122010824-A

Abstract

The invention relates to the technical field of compound synthesis, in particular to an amide derivative containing trifluoromethyl pyridine, and a synthesis method and application thereof. The structural general formula of the amide derivative is shown as formula I, formula II and formula III. The amide derivative has novel molecular skeleton, has excellent antifungal activity on tomato gray mold, rice sheath blight and rape sclerotium disease, and has good protection and therapeutic activity on tomato crops. The invention also provides a synthesis method and application of the amide derivative containing the trifluoromethyl pyridine.

Inventors

  • LI TINGTING
  • QIN YUELING
  • WANG RUI
  • CHEN MING
  • WU WENQIAN
  • YANG WENJUN
  • LUO XIANGYAN

Assignees

  • 贵州大学

Dates

Publication Date
20260512
Application Date
20260130

Claims (10)

  1. 1. An amide derivative containing trifluoromethyl pyridine is characterized in that the structural general formula of the amide derivative is shown as formula I, formula II and formula III: A formula I; A formula II; Formula III; Wherein R is selected from any one of phenyl, halogenated phenyl, phenyl-C1-C4 alkyl, phenyl-C1-C4 alkoxy and 5-6 membered heterocycle; R 1 is selected from any one of benzyl, methyl and ethyl; r 2 is selected from any one of phenyl, 5-6 membered heterocycle, 5-6 membered halogeno heterocycle, 5-6 membered heterocycle-C1-C6 alkyl and 5-6 membered halogeno heterocycle-C1-C6 alkyl; R 3 is selected from 5-6 membered halogenated heterocycles.
  2. 2. The amide derivative according to claim 1, wherein the amide derivative is any one of the following compounds: 。
  3. 3. a method for synthesizing the amide derivative according to claim 1 or 2, comprising the steps of: 1) Mixing and stirring nitromethane, potassium hydroxide and dimethyl sulfoxide under the nitrogen atmosphere, and then mixing with the compound 1 to perform an arylation reaction to obtain a compound 2; mixing the compound 2 with absolute ethyl alcohol and stannous chloride dihydrate, and then carrying out reduction reaction to obtain a compound 3; mixing the compound 4 with selenium dioxide and pyridine, and then carrying out an oxidation reaction to obtain a compound 5; Mixing the compound 5 with dichloromethane, N-dimethylformamide and oxalyl chloride, and then carrying out substitution reaction to obtain a compound 6; mixing the compound 3 with the compound 6 and diisopropylethylamine, and then carrying out condensation reaction to obtain a compound 7; mixing the compound 7 with methanol, hydroxylamine hydrochloride and potassium carbonate, and performing condensation reaction to obtain a compound 8; mixing the compound 8 with sodium hydride, N-dimethylformamide and halogenated hydrocarbon, and carrying out alkylation reaction to obtain a compound shown in a formula I; 2) Mixing the compound 7 with primary amine and tetraisopropyl titanate, and performing condensation reaction to obtain a compound shown in a formula II; 3) Mixing the compound shown in the formula II with sodium borohydride and absolute ethyl alcohol, and then carrying out reduction reaction to obtain a compound shown in the formula III; the structural formula of the compounds 1-8 is as follows: 。
  4. 4. The synthesis method according to claim 3, wherein the conditions of the arylation reaction comprise a temperature of 20-30 ℃ and a time of 3-5 h, wherein the volume of nitromethane, the mass of potassium hydroxide, the volume of dimethyl sulfoxide and the mass of compound 1 are 12.48mL:10.39g:150mL:10g; The mass of the compound 2, the volume of absolute ethyl alcohol and the mass of stannous chloride dihydrate are 2.41g:70mL:45.13g, and the reduction reaction conditions comprise the temperature of 75-85 ℃ and the time of 4-10 h; the molar ratio of the compound 4 to the mass of selenium dioxide and the volume ratio of pyridine are 5mmol to 1.11g to 20mL, and the oxidation reaction conditions comprise the temperature of 90-110 ℃ and the time of 2-8 h; The molar ratio of the compound 5 to the volume of dichloromethane, the number of drops of N, N-dimethylformamide and the volume ratio of oxalyl chloride are 2mmol:20 mL:1-2 drops:0.18 mL, and the substitution reaction conditions comprise the temperature of 0-30 ℃ and the time of 0.5-2 h; The volume ratio of the mass of the compound 3 to the mol of the compound 6 and diisopropylethylamine is 505.4mg to 2mmol to 0.7mL, and the condensation reaction conditions comprise the temperature of 0-40 ℃ and the time of 0.5-4 h; The molar ratio of the compound 7 to the volume of methanol, the mass of hydroxylamine hydrochloride and the mass of potassium carbonate is 3mmol:25mL:625.39mg:621.92mg, and the condensation reaction conditions comprise that the temperature is 50-70 ℃ and the time is 6-12 h; The molar ratio of the compound 8 to the mass of sodium hydride, the volume of N, N-dimethylformamide and the molar ratio of halogenated hydrocarbon are 0.15mmol:10.8mg:2mL:0.23mmol, and the alkylation reaction conditions comprise no temperature of 0-30 ℃ and the time of 1-6 h.
  5. 5. The synthesis method according to claim 3, wherein the volume ratio of the mole of the compound 7 to the mole of the primary amine and the tetraisopropyl titanate in the step 2) is 0.15mmol:0.45 mmol:1-2 mL, and the condensation reaction condition comprises that the temperature is 20-30 ℃ and the time is 6-24 h.
  6. 6. The synthesis method according to claim 3, wherein the molar ratio of the compound shown in the formula II to sodium borohydride in the step 3) is 0.15 mmol/17 mg/1 mL, and the reduction reaction conditions include a temperature of 20-30 ℃ and a time of 0.5-1 h.
  7. 7. Use of the amide derivatives according to claim 1 or 2for controlling fungal plant diseases.
  8. 8. The use according to claim 7, wherein the amide derivative is used at a concentration of 0.195 to 400 μg/mL.
  9. 9. The use according to claim 7, wherein the plant fungal disease comprises one or more of rice sheath blight, rape sclerotinia, cucumber fusarium wilt, pepper fusarium wilt, tomato gray mold, blueberry gray mold, wheat scab, phomopsis, yellow aspergillosis and pepper anthracnose.
  10. 10. An antibacterial agent against plant fungal diseases, characterized by comprising the amide derivative according to claim 1 or 2; The plant fungal diseases comprise one or more of rice sheath blight, rape sclerotinia rot, cucumber fusarium wilt, pepper fusarium wilt, tomato gray mold, blueberry gray mold, wheat scab, phomopsis, yellow aspergillosis and pepper anthracnose.

Description

Amide derivative containing trifluoromethyl pyridine and synthetic method and application thereof Technical Field The invention relates to the technical field of compound synthesis, in particular to an amide derivative containing trifluoromethyl pyridine, and a synthesis method and application thereof. Background Fungi are important factors threatening agricultural production, causing huge losses to agricultural production. Fungi infects crop plants, destroys the physiological structure and metabolic processes of the plants, causes various diseases and rapidly spreads, even some fungi can generate toxins harmful to human beings and animals, and enters a food chain through agricultural products, so that huge harm and economic loss are caused. At present, bactericides are a main means for scientifically preventing and controlling fungal diseases and guaranteeing agricultural production. However, the wide use of chemical pesticides leads to the problems of drug resistance of pathogenic fungi, serious soil and water pollution and the like. Therefore, it is urgent to create a novel green bactericide which is efficient, low in risk and excellent in crop safety. Amide functionalities are widely available in the biological and synthetic fields, covering proteins, polymers, agrochemicals and pharmaceutical products. In the field of agrochemicals, amide derivatives exhibit diverse and broad-spectrum biological activities including antifungal, insecticidal, herbicidal and antiviral activities, and their synthesis and biological evaluation have long been an important topic of agrochemical chemistry. Numerous carboxamide containing bactericides have been commercialized to date, with the succinate dehydrogenase inhibitor (SDHIs) being one of the fastest growing, most active broad-spectrum fungicide classes in recent years. Notably, fragments of trifluoromethylpyridine have been introduced into portions of SDHI and other commercial bactericides such as fluopicolide, fluopyram and fluoride ether bacteria amide containing the fragments exhibit excellent protective efficacy against a variety of fungal diseases. As a biologically active fragment of important application value, trifluoromethylpyridine plays a key role in drug design, and is of great interest in the field of antifungal agent development. Compounds containing-CF 3 often exhibit significant biological activity and unique physicochemical properties due to the strong electronegativity, high stability and lipophilicity of the trifluoromethyl group. The introduction of the trifluoromethyl pyridine fragment can enhance the antifungal activity of antibiotics and improve the drug effect of the antibiotics on drug-resistant strains. In addition, the building blocks have been widely used in the design of novel antifungal agents to inhibit the growth and multiplication of fungi by targeting specific sites on the cell wall or membrane. Therefore, the trifluoromethyl pyridine fragment and the amide structure are spliced, and the antifungal candidate compound with potential crop protection application prospect is expected to be generated. Disclosure of Invention In order to solve the problems, the invention provides an amide derivative containing trifluoromethyl pyridine, a synthesis method and application thereof, wherein the amide derivative has a novel molecular skeleton, has excellent antifungal activity on tomato gray mold, rice sheath blight and rape sclerotium disease, and has good protection and treatment activity on tomato crops. In order to achieve the above object, the present invention provides the following technical solutions: the invention provides an amide derivative containing trifluoromethyl pyridine, which has a structural general formula shown in formula I, formula II and formula III: A formula I; A formula II; Formula III; Wherein R is selected from any one of phenyl, halogenated phenyl, phenyl-C1-C4 alkyl, phenyl-C1-C4 alkoxy and 5-6 membered heterocycle; R 1 is selected from any one of benzyl, methyl and ethyl. R 2 is selected from any one of phenyl, 5-6 membered heterocycle, 5-6 membered halogeno heterocycle, 5-6 membered heterocycle-C1-C6 alkyl and 5-6 membered halogeno heterocycle-C1-C6 alkyl; R 3 is selected from 5-6 membered halogenated heterocycles. Preferably, the amide derivative is any one of the following compounds: 。 the invention also provides a synthesis method of the amide derivative, which comprises the following steps: 1) Mixing and stirring nitromethane, potassium hydroxide and dimethyl sulfoxide under the nitrogen atmosphere, and then mixing with the compound 1 to perform an arylation reaction to obtain a compound 2; mixing the compound 2 with absolute ethyl alcohol and stannous chloride dihydrate, and then carrying out reduction reaction to obtain a compound 3; mixing the compound 4 with selenium dioxide and pyridine, and then carrying out an oxidation reaction to obtain a compound 5; Mixing the compound 5 with dichloromethane, N-di