Search

CN-121990998-A - Preparation method of uracil-containing iminoaryl compound

CN121990998ACN 121990998 ACN121990998 ACN 121990998ACN-121990998-A

Abstract

The invention belongs to the field of organic chemical synthesis, and particularly relates to a preparation method of an imino aryl compound containing uracil. The uracil-containing iminoaryl compounds From Is prepared through a series of reactions. The purity of the product finally obtained by the synthetic route is above 99%, meanwhile, no high toxicity and waste water difficult to treat are generated in the process route, the raw materials are cheap and easy to purchase, the reaction process is simple, the condition is mild, the requirement on equipment is low, the process cost is low, and the industrial production is easy to carry out.

Inventors

  • PENG LIANG
  • SHAO ZHUZHOU
  • HAN LONGKUN
  • LI YOU

Assignees

  • 山东清原农冠作物科学有限公司

Dates

Publication Date
20260508
Application Date
20241105

Claims (8)

  1. 1. The preparation method of the uracil-containing iminoaryl compound is characterized by comprising the following steps: (1) Reducing the compound VII to obtain a compound VIII; (2) Reacting the compound VIII with hydroxylamine hydrochloride or ammonium bisulfate to obtain a compound IX; (3) Reacting the compound IX with IX-a to obtain an iminoaryl compound X containing uracil; The synthetic route is as follows: Wherein L represents halogen.
  2. 2. The process according to claim 1, wherein the step (1) is carried out in the presence of a catalyst and a solvent, preferably the solvent is at least one selected from formic acid, acetic acid, propionic acid, ethanol, tetrahydrofuran, 1, 4-dioxane, toluene or water; the step (2) is carried out in the presence of a solvent, preferably an alcohol, and/or The step (3) is carried out in the presence of a base and a polar solvent, preferably at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate or potassium bicarbonate, and/or the polar solvent is at least one of acetonitrile, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, sulfolane or N-methylpyrrolidone, and more preferably the base is in a powder form.
  3. 3. The preparation method according to claim 1 or 2, wherein the compound VII is obtained by cyclizing a compound V and a compound V-a to obtain VI and then methylation, and the reaction formula is as follows: Wherein R 1 is selected from alkyl or aryl, R 2 is selected from alkyl or aryl, and the aforementioned "aryl" is optionally substituted with at least one group selected from hydroxy, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkylthio or alkylsulfonyl; Preferably, R 1 is selected from C1-C8 alkyl or aryl, R 2 is selected from C1-C8 alkyl or aryl, the foregoing "aryl" is optionally substituted with at least one group selected from hydroxy, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, haloC 1-C8 alkyl, haloC 2-C8 alkenyl, haloC 2-C8 alkynyl, C1-C8 alkoxy, haloC 1-C8 alkoxy, C1-C8 alkoxycarbonyl, C1-C8 alkylthio or C1-C8 alkylsulfonyl; More preferably, R 1 is selected from C1-C4 alkyl or phenyl, R 2 is selected from methyl, ethyl, isopropyl or phenyl, the foregoing "phenyl" being optionally substituted with at least one group selected from hydroxy, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, haloC 1-C6 alkyl, haloC 2-C6 alkenyl, haloC 2-C6 alkynyl, C1-C6 alkoxy, haloC 1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylthio or C1-C6 alkylsulfonyl; Preferably, the cyclization reaction is performed in the presence of a solvent, a base, more preferably, the solvent is selected from at least one of acetonitrile, tetrahydrofuran, toluene, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, 1, 3-dimethyl-2-imidazolidinone, sulfolane, or N-methylpyrrolidone, the base is selected from at least one of an inorganic base and an organic base, and/or the methylating agent is selected from at least one of methyl iodide, methyl chloride, methyl bromide, dimethyl sulfate, or dimethyl carbonate.
  4. 4. A process according to claim 3, wherein compound V is obtained by reacting compound IV with chloroformate compound IV-a, the reaction formula being as follows: preferably, the reaction is carried out in the presence of a solvent, more preferably, a base is also present in the reaction, further preferably, the solvent is selected from at least one of acetonitrile, tetrahydrofuran, ethyl acetate, dichloromethane, 1, 2-dichloroethane, toluene, xylene, chlorobenzene or dichlorobenzene, and/or the base is selected from at least one of an organic base or an inorganic base.
  5. 5. The preparation method according to claim 4, wherein the compound IV is obtained by a reduction reaction of a compound III and a hydrogenation reagent, and the reaction formula is as follows: Preferably, the reduction reaction is carried out in the presence of a hydrogenation solvent and a hydrogenation catalyst, more preferably the hydrogenation solvent is selected from at least one of methanol, ethanol, isopropanol or water, and/or the hydrogenation catalyst is selected from at least one of sodium hydrosulfite, ferric trichloride, iron powder, copper powder, raney nickel, palladium carbon or platinum carbon.
  6. 6. The preparation method according to claim 5, wherein the compound III is obtained by fluoridation of a compound II and a fluoride salt, and the reaction formula is as follows: Preferably, the fluorination reaction is carried out in the presence of a fluorinated solvent, more preferably, the fluorinated solvent is selected from at least one of acetonitrile, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, 1, 3-dimethyl-2-imidazolidinone, sulfolane or N-methylpyrrolidone, and/or the fluoride salt is selected from at least one of potassium fluoride, sodium fluoride, cesium fluoride, amine fluoride or tetrabutylammonium fluoride.
  7. 7. The method according to claim 6, wherein the compound II is obtained by nitration of the compound I with nitric acid, and the reaction formula is as follows: Preferably, the nitration is carried out in the presence of a nitration catalyst, more preferably a nitration solvent is added during the reaction, still more preferably the nitration solvent is selected from at least one of dichloromethane, dichloroethane, chloroform, acetic acid, trifluoroacetic acid or water and/or the nitration catalyst is selected from at least one of concentrated sulfuric acid, acetic anhydride or trifluoroacetic anhydride.
  8. 8. The process according to any one of claims 1 to 7, wherein the carbon atom to which the L group of step (3) is attached is in the R configuration, which has the following reaction formula:

Description

Preparation method of uracil-containing iminoaryl compound Technical Field The invention belongs to the field of organic chemical synthesis, and particularly relates to a preparation method of an imino aryl compound containing uracil. Background Various production processes of phenyl uracil herbicide compounds exist in the market, but the problems of high three wastes, high toxicity, high production difficulty, low yield and product purity and the like generally exist, and development of a synthesis method suitable for industrial mass production is needed. For example, patent CN113880774 discloses a method for preparing 2-chloro-4-fluoro-5- (3-methyl-2, 6-dione-4-trifluoromethyl-2, 3-dihydropyrimidinyl-1 (6H) -yl) benzaldehyde by using 2-fluoro-4-chloro-5-methylaniline as a raw material and sequentially carrying out acylation, cyclization, methylation, bromination and hydrolysis. The key material 2-fluoro-4-chloro-5-methylaniline used in the method has no bulk goods supply and is not easy to purchase, and carbon tetrachloride is used as a solvent in the methyl halogenation process, so that the problems of high toxicity and the like exist, and the purity of the obtained product is low, so that the method is not beneficial to industrial production. Patent CN115124476 discloses that 2-chloro-4-chloro-5-trifluoromethylaniline is used as a raw material, and the 2-chloro-4-fluoro-5- (3-methyl-2, 6-dione-4-trifluoromethyl-2, 3-dihydropyrimidinyl-1 (6H) -yl) benzaldehyde is prepared by the procedures of acylation, cyclization, reduction, hydrolysis and the like in sequence. Patent CN 114656407 discloses that 2, 4-dichlorotoluene is used as raw material, and is subjected to procedures of nitration, fluorination, reduction, cyclization, bromination, hydrolysis and the like in sequence to prepare 2-chloro-4-fluoro-5- (3-methyl-2, 6-dione-4-trifluoromethyl-2, 3-dihydropyrimidinyl-1 (6H) -yl) benzaldehyde. Disclosure of Invention In order to solve the problems in the prior art, the invention provides a preparation method of an iminoaryl compound containing uracil. The technical scheme adopted by the invention is as follows: A method for preparing an iminoaryl compound containing uracil, which comprises the following steps: (1) Reducing the compound VII to obtain a compound VIII; (2) Reacting the compound VIII with hydroxylamine hydrochloride or hydroxylamine sulfate to obtain a compound IX; (3) Reacting the compound IX with IX-a to obtain an iminoaryl compound X containing uracil; The synthetic route is as follows: Wherein L represents halogen. Preferably, the step (1) is carried out in the presence of a catalyst and a solvent, more preferably the solvent is at least one selected from formic acid, acetic acid, propionic acid, ethanol, tetrahydrofuran, 1, 4-dioxane, toluene or water, and/or the catalyst is Raney nickel or nickel-aluminum alloy. Preferably, the step (2) is carried out in the presence of a solvent, more preferably, the solvent is an alcohol (e.g., methanol, ethanol, isopropanol, t-butanol, etc.). Preferably, the step (3) is performed in the presence of a base and a polar solvent, more preferably, the base is selected from at least one of sodium hydroxide, sodium carbonate, sodium bicarbonate, potassium hydroxide, potassium carbonate or potassium bicarbonate, and/or the polar solvent is selected from at least one of acetonitrile, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, sulfolane or N-methylpyrrolidone, more preferably, the base is in the form of a powder. In a specific embodiment, the compound VII is obtained by cyclizing a compound V and a compound V-a1 to obtain VI and then methylation, or by cyclizing a compound V and a compound V-a2, wherein the reaction formula is as follows: Wherein R 1 is selected from alkyl or aryl, R 2 is selected from alkyl or aryl, and the aforementioned "aryl" is optionally substituted with at least one group selected from hydroxy, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, alkoxycarbonyl, alkylthio or alkylsulfonyl; Preferably, R 1 is selected from C1-C8 alkyl or aryl, R 2 is selected from C1-C8 alkyl or aryl, the foregoing "aryl" is optionally substituted with at least one group selected from hydroxy, halogen, cyano, nitro, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, haloC 1-C8 alkyl, haloC 2-C8 alkenyl, haloC 2-C8 alkynyl, C1-C8 alkoxy, haloC 1-C8 alkoxy, C1-C8 alkoxycarbonyl, C1-C8 alkylthio or C1-C8 alkylsulfonyl; More preferably, R 1 is selected from C1-C4 alkyl or phenyl, R 2 is selected from methyl, ethyl, isopropyl or phenyl, the foregoing "phenyl" being optionally substituted with at least one group selected from hydroxy, halogen, cyano, nitro, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, haloC 1-C6 alkyl, haloC 2-C6 alkenyl, haloC 2-C6 alkynyl, C1-C6 alkoxy, haloC 1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylthio or C1-C6 alkylsulfonyl; Preferably, the cyclization reaction is performed in