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CN-121990994-A - Imidazole derivative and preparation method and application thereof

CN121990994ACN 121990994 ACN121990994 ACN 121990994ACN-121990994-A

Abstract

The invention discloses an imidazole derivative shown in a formula (I), Or a salt, stereoisomer or oxynitride thereof, wherein R and R 1 are as defined in the description. The compound shown in the formula (I) can be used as an agent for killing harmful microorganisms, and has a good effect on fungus causing damping-off.

Inventors

  • LI GUDONG

Assignees

  • 帕潘纳(北京)科技有限公司

Dates

Publication Date
20260508
Application Date
20241101

Claims (12)

  1. 1. A compound of the formula (I), Salts thereof, stereoisomers thereof or oxynitride, Wherein R is H, C 1 -C 6 alkyl or halogenated C 1 -C 6 alkyl; R 1 is R 2 is H, C 1 -C 6 alkyl or halogenated C 1 -C 6 alkyl; Wherein, the Representing the connection end.
  2. 2. A compound, salt, stereoisomer or oxynitride thereof according to claim 1, characterized in that R and R 2 are each independently selected from H, methyl, ethyl, propyl or trifluoromethyl.
  3. 3. The compound, salt, stereoisomer or oxynitride thereof according to claim 1 or 2, characterized in that the compound of formula (I) is a compound of formula A, Wherein R and R 2 are as defined in claim 1 or 2.
  4. 4. The compound, salt, stereoisomer or oxynitride thereof according to claim 1 or 2, characterized in that the compound of formula (I) is a compound of formula B, Wherein R is as defined in claim 1 or 2.
  5. 5. A compound, salt thereof, stereoisomer thereof or oxynitride compound according to claim 1, characterized by being selected from the group consisting of,
  6. 6. A process for the preparation of compound a according to claim 3, characterized by the following synthetic route: Wherein R and R 2 are as defined in claim 3, X is a leaving group, preferably halogen; Preferably, the preparation method comprises the following steps of reacting a compound (5) with thionyl chloride to form an acyl chloride compound (5), reacting the compound (5) with a 2-fluoroaniline compound in an organic solvent A, adding an acid-binding agent, and then obtaining the compound A, wherein the organic solvent A is one or more of acetonitrile, 1, 2-dichloroethane, dichloromethane and N, N-dimethylformamide, and the acid-binding agent is one of sodium carbonate, potassium carbonate, triethylamine and diisopropylethylamine.
  7. 7. A process for the preparation of compound B as claimed in claim 4, wherein the synthetic route is as follows: Wherein R is H, C 1 -C 6 alkyl or halogenated C 1 -C 6 alkyl; Preferably, the preparation method comprises the steps of carrying out substitution reaction on a compound (4') and a compound R-L to generate a compound (5), wherein L is a leaving group, preferably halogen, reacting the compound (5) with hydroxylamine hydrochloride to form oxime, then reacting the oxime with methyl 2-chloropropionate in an organic solvent B, adding inorganic base into the organic solvent B to obtain the compound B, wherein the organic solvent B is one or more of acetonitrile, tetrahydrofuran, acetone and N, N-dimethylformamide, and the inorganic base is one of sodium carbonate and potassium carbonate.
  8. 8. A process for producing compound (4'), characterized by the following synthetic route: Preferably, the preparation method comprises the following steps: the method comprises the steps of (1) reacting a compound (3) with a chlorinating agent to synthesize a compound (4), wherein the chlorinating agent in the step (1) is preferably one or more selected from chlorine, sodium chlorate, calcium hypochlorite, N-chlorosuccinimide, dichlorohydantoin, trichloroisocyanuric acid and sulfonyl chloride, and the molar ratio of the chlorinating agent to the compound (3) is 1-2:1; The compound (4) is reacted with an oxide in the presence of a phase transfer catalyst A, an accelerating catalyst B and an oxidizing catalyst C to synthesize the compound (4'), preferably, the phase transfer catalyst A in the step (2) is selected from one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, benzyltriethylammonium chloride and tetramethylammonium chloride, the accelerating catalyst B is selected from one or more of potassium bromide and sodium bromide, the oxidizing catalyst C is selected from one or more of 2, 6-tetramethylpiperidine oxide and 4-hydroxy-2, 6-tetramethylpiperidine oxide, the oxide is selected from one or more of sodium hypochlorite, hypochlorous acid, sodium hypochlorite, N-chlorosuccinimide and sulfonyl chloride, the molar ratio of the phase transfer catalyst A to the compound (4) is 0.01-0.2:1, the molar ratio of the accelerating catalyst B to the compound (4) is 0.01-0.25:0.1, and the molar ratio of the oxidizing catalyst B to the compound (4) is 0.01-0.2:1, the molar ratio of the oxidizing catalyst B to the compound (4) is 0.1:1.5.
  9. 9. A preparation method of the compound (3) is characterized in that the synthetic route is as follows: Preferably, the preparation method comprises the following steps: The method comprises the steps of (a) reacting a compound (1) with a metal glycolate under the action of a phase transfer catalyst to obtain a compound (2), wherein the metal glycolate is preferably selected from sodium salt, potassium salt or calcium salt of glycolic acid, the molar ratio of the metal glycolate to alpha-halogenated-p-methylacetophenone is 1-1.5:1, the phase transfer catalyst is one or more of tetrabutylammonium bromide, tetrabutylammonium chloride and benzyltriethylammonium chloride, and the mass ratio of the phase transfer catalyst to the compound (1) is 0.05-0.2:1; The compound (2) is subjected to rearrangement ring-closing reaction with an ammonia source under the action of organic acid to obtain a compound (3), preferably, the organic acid is selected from one or more of formic acid, acetic acid and propionic acid, the molar ratio of the organic acid to the compound (2) is 1-10:1, the ammonia source is one or more of ammonia water, ammonium formate, ammonium acetate, ammonium isobutyrate and hexamethyldisilazane, and the molar ratio of the ammonia source to the compound (2) is 3-10:1.
  10. 10. The compound is used as a carrier of a compound, Wherein R is H, C 1 -C 6 alkyl or halogenated C 1 -C 6 alkyl, preferably H or methyl.
  11. 11. The compound is used as a carrier of a compound, Wherein R is H, C 1 -C 6 alkyl or halogenated C 1 -C 6 alkyl, preferably H or methyl.
  12. 12. A fungicidal composition comprising a compound according to any one of claims 1 to 5, a salt thereof, a stereoisomer thereof or an oxynitride compound.

Description

Imidazole derivative and preparation method and application thereof Technical Field The invention belongs to the field of pesticide synthesis, and particularly relates to an imidazole derivative, a preparation method thereof and application thereof as a bactericide. Technical Field Through investigation, more than 8 ten thousand microorganisms harmful to crops worldwide exist, so that the crop diseases are serious, and huge economic losses are caused. Historically, there have been a number of fatalities that have been hungry to a large population due to the pandemic of plant diseases. In recent years, a large number of novel agricultural bactericides with different skeleton structures are appeared on the market for preventing and treating various crop diseases. There are data indicating that the market size of the germicides in China is nearly 60 hundred million yuan. Therefore, the discovery and preparation of the novel bactericide are still of great significance and have wide market prospect. Imidazole structures are widely used in the existing bactericides such as prochloraz, fenamidone, imazalil, oxazamate and the like. The stronger bactericidal effect of the medicines is enough to reflect the specificity of imidazole structures. Therefore, the structural design and preparation of imidazole derivatives are extremely potential research directions in the discovery of novel bactericides. Based on this, the applicant has completed the present invention. Disclosure of Invention The invention aims to provide an imidazole derivative with excellent bactericidal effect. Specifically, the invention firstly provides a compound of formula (I), Salts thereof, stereoisomers thereof or oxynitride, Wherein R is H, C 1-C6 alkyl or halogenated C 1-C6 alkyl; R 1 is R 2 is H, C 1-C6 alkyl or halogenated C 1-C6 alkyl; wherein "" "indicates a connecting terminal. Preferably, the compound of formula (I) is a compound of formula A, Wherein R and R 2 are as defined above. Preferably, the compound of formula (I) is a compound of formula B, Wherein R is as defined above. The invention also provides a preparation method of the compound A, which comprises the following synthetic route: Wherein R and R 2 are as defined above and X is a leaving group. The invention also provides a preparation method of the compound B, which comprises the following synthetic route: wherein R is H, C 1-C6 alkyl or halogenated C 1-C6 alkyl. The invention also provides a preparation method of the compound (4'), which is characterized in that the synthetic route is as follows: the invention also provides a preparation method of the compound (3), which comprises the following synthetic route: the present invention also provides the following intermediate compounds: the present invention also provides a fungicidal composition comprising the compound of the present invention, a salt thereof, a stereoisomer thereof or an oxynitride compound. Detailed Description For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations thereof such as "comprises" or "comprising", etc. will be understood to include the stated elements or steps without excluding the presence of other material elements or steps. In addition, numerous specific details are set forth in the following description in order to provide a better illustration of the invention. It will be understood by those skilled in the art that the present invention may be practiced without some of these specific details. In some embodiments, materials, methods, means, etc. well known to those skilled in the art are not described in detail in order to highlight the gist of the present invention. For the purpose of more clearly illustrating the objects, technical solutions and advantages of the embodiments of the present invention, the technical solutions of the embodiments of the present invention will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention. Throughout the specification and claims, unless explicitly stated otherwise, the term "comprise" or variations thereof such as "comprises" or "c