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CN-121974898-A - Substituted benzoxazinone-isoxazoline compound and preparation method and application thereof

CN121974898ACN 121974898 ACN121974898 ACN 121974898ACN-121974898-A

Abstract

The invention discloses a substituted benzoxazinone-isoxazoline compound, a preparation method and application thereof. The method comprises the steps of taking DMF as a solvent, enabling ethyl bromoacetate and a compound (II) to react to form a compound (III), cyclizing the compound (IV) in the presence of acetic acid and reduced iron powder to obtain a compound (IV), reacting the compound (IV) with hydroxylamine hydrochloride to form a compound (V), reacting the compound (V) with NCS and MMA in the presence of TEA to generate a compound (VI), reacting the compound (VI) with bromopropyne to obtain a substituted benzoxazinone-isoxazoline compound, and reacting and condensing the compound (VI) with alcohol or amine after alkaline hydrolysis to obtain a target product. The result of the weeding activity test shows that under the condition of 100ppm concentration, the compounds I1, I2, I4, I15 and I16 have good inhibiting effect on rape, show excellent weeding activity and have good control effect on invading organism aster.

Inventors

  • MIN LIJING
  • HAN FUXIANG
  • LIU XINGHAI
  • TANG CHAOYANG
  • ZHANG LIQIN

Assignees

  • 湖州师范学院
  • 浙江工业大学

Dates

Publication Date
20260505
Application Date
20251230

Claims (10)

  1. 1. The substituted benzoxazinone-isoxazoline compound is characterized in that the structural formula is shown in the formula (I): In the formula (I), the substituent R 1 is hydrogen or chlorine, the substituent R 2 is alkyl or cycloalkyl, and the substituent R 3 is alkyl or alkoxy.
  2. 2. The substituted benzoxazinone-isoxazoline compound according to claim 1, wherein the substituent R 2 is methyl, ethyl, isopropyl, n-butyl, cyclopentyl or cyclohexyl, and the substituent R 3 is methoxy, ethoxy, cyclopropyl or isopropyl.
  3. 3. A process for the preparation of a substituted benzoxazinone-isoxazoline compound according to claim 1, characterized by comprising the steps of: 1) Heating ethyl bromoacetate and a compound shown as a formula (II) by taking DMF as a solvent to react to generate the compound shown as a formula (III); 2) Heating and reacting the compound shown in the formula (III) obtained in the step 1) with reduced iron powder by taking acetic acid as a solvent, firstly reducing nitro into amino, and then carrying out intramolecular cyclization under the catalysis of acetic acid to generate the compound shown in the formula (IV); 3) Heating and refluxing the compound shown in the formula (IV) obtained in the step 2) with hydroxylamine hydrochloride by taking absolute ethyl alcohol as a solvent and TEA as an acid binding agent to generate a compound shown in the formula (V); 4) Reacting the compound shown in the formula (V) obtained in the step 3) with NCS and MMA at room temperature by taking DMF as a solvent and TEA as an acid binding agent to generate a compound shown in the formula (VI); 5) Reacting the compound shown in the formula (VI) obtained in the step 4) with bromopropyne at room temperature by taking DMF as a solvent and K 2 CO 3 as an acid-binding agent to obtain a substituted benzoxazinone-isoxazoline compound shown in the formula (VII); 6) Reacting the compound shown in the formula (VII) obtained in the step 5) with sodium hydroxide by taking anhydrous as a solvent to obtain an alkaline hydrolysate of the substituted benzoxazinone-isoxazoline compound shown in the formula (VII); 7) Taking DCM as a solvent and EDCl and DMAP as condensing agents, and carrying out condensation reaction on the alkaline hydrolysate of the substituted benzoxazinone-isoxazoline compound shown in the formula (VII) obtained in the step 6) and R 2 OH or R 3 NH 2 to obtain the substituted benzoxazinone-isoxazoline compound shown in the formula (I); the reaction process is as follows: Wherein R 1 is hydrogen or chlorine, R 2 is alkyl or cycloalkyl, and R 3 is alkyl or alkoxy.
  4. 4. The process for producing a substituted benzoxazinone-isoxazoline compound according to claim 3, wherein the mass ratio of the compound represented by the formula (II) to ethyl bromoacetate in step 1) is 1:1.5-2, the reaction temperature is 80 ℃ to 85 ℃, and the reaction time is 5.5 to 6.5 hours, preferably 6 hours.
  5. 5. The process for producing a substituted benzoxazinone-isoxazoline compound according to claim 3, wherein the mass ratio of the compound represented by the formula (III) to the reduced iron powder in step 2) is 1:4-6, the reaction temperature is 80 ℃ to 85 ℃, and the reaction time is 2.5 to 3.5 hours, preferably 3 hours.
  6. 6. The process for producing a substituted benzoxazinone-isoxazoline compound according to claim 3, wherein the mass ratio of the compound represented by the formula (IV) in step 3) to the substance of hydroxylamine hydrochloride is 1:1.5-3.
  7. 7. The process for producing a substituted benzoxazinone-isoxazoline compound according to claim 3, wherein the ratio of the amount of the compound represented by the formula (V) in step 4) to the amounts of NCS, TEA and MMA is 1:1.2 to 2.5:1.2 to 2.5.
  8. 8. The process for producing a substituted benzoxazinone-isoxazoline compound according to claim 3, wherein the mass ratio of the compound represented by the formula (VI) to the bromopropyne compound in step 5) is 1:1.2-3.
  9. 9. The process for producing a substituted benzoxazinone-isoxazoline compound according to claim 3, wherein the mass ratio of the compound represented by the formula (VII), EDCl, DMAP to the substance of R 2 OH or R 3 NH 2 in step 7) is 1:1.2 to 2.5:0.1 to 0.2:2 to 2.5.
  10. 10. Use of a substituted benzoxazinone-isoxazoline compound according to claim 1 or 2 as herbicide.

Description

Substituted benzoxazinone-isoxazoline compound and preparation method and application thereof Technical Field The invention belongs to the technical field of medicine synthesis, and particularly relates to a substituted benzoxazinone-isoxazoline compound, and a preparation method and application thereof. Background Heterocyclic compounds are widely available in nature and are the most numerous organic compounds. The most common hetero atoms of the heterocyclic structure are nitrogen atoms, sulfur atoms and oxygen atoms, and the hetero atoms have wide biological activity, are easy to carry out structural modification and can often endow molecules with new biological functions. In particular to nitrogen-containing and oxygen-containing heterocyclic compounds (such as benzoxazinone, isoxazoline and the like) with novel structures become hot spots for the creation of new pesticides. The development of heterocyclic compounds with novel structures by taking active natural products or known active frameworks as the lead, so as to obtain high-efficiency and broad-spectrum biological activity, has become one of the most active development directions in the field of pesticide chemistry in recent years. Benzoxazinone is taken as an important nitrogenous-oxygen bi-heterocyclic skeleton, is a core structural unit of a Plurality of Protoporphyrinogen Oxidase (PPO) inhibitor herbicides, and shows excellent herbicidal activity. The isoxazoline is taken as another five-membered heterocyclic ring containing N, O atoms, has unique electronic property and wide biological activity, has small toxicity to human bodies and is easy to modify in structure, and is often introduced into drug molecules as a pharmacophore. Compared with other types of herbicides, the PPO inhibitor has the advantages of good selectivity, low dosage, environmental friendliness, wide weeding spectrum, difficulty in generating resistance of weeds and the like, and the development of the novel PPO inhibitor has important significance. The existing research shows that the isoxazoline fragment with high biological activity is introduced into the benzoxazinone skeleton through a molecular hybridization strategy, so that a synergistic effect is expected to be generated, and the problem of resistance faced by the existing herbicide is solved. Based on the design thought, the invention takes a classical benzoxazinone structure as a lead skeleton, utilizes a bioisosteric principle and a substructure splicing method, creatively introduces an isoxazoline active fragment on the basis of keeping key active sites such as N-substituted propargyl side chains and the like, and designs and synthesizes a series of novel isoxazolinyl-containing benzoxazinone compounds. The invention aims to obtain a novel herbicide variety with higher weeding activity and higher crop safety through the structural optimization. Disclosure of Invention In view of the problems existing in the prior art, the invention aims to provide a substituted benzoxazinone-isoxazoline compound, a preparation method and application thereof, In order to achieve the purpose, the invention has the technical scheme that the invention defines the substituted benzoxazinone-isoxazoline compound, and the structural formula of the compound is shown as the formula (I): In the formula (I), the substituent R 1 is hydrogen or chlorine, the substituent R 2 is alkyl or cycloalkyl, and the substituent R 3 is alkyl or alkoxy. Further, the invention defines that substituent R 2 is methyl, ethyl, isopropyl, n-butyl, cyclopentyl or cyclohexyl, and substituent R 3 is methoxy, ethoxy, cyclopropyl or isopropyl. Further, the invention defines a preparation method of the substituted benzoxazinone-isoxazoline compound, which specifically comprises the following steps: 1) Heating ethyl bromoacetate and a compound shown as a formula (II) by taking DMF as a solvent to react to generate the compound shown as a formula (III); 2) Heating and reacting the compound shown in the formula (III) obtained in the step 1) with reduced iron powder by taking acetic acid as a solvent, firstly reducing nitro into amino, and then carrying out intramolecular cyclization under the catalysis of acetic acid to generate the compound shown in the formula (IV); 3) Heating the compound shown in the formula (IV) obtained in the step 2) and hydroxylamine hydrochloride to reflux reaction by taking absolute ethyl alcohol as a solvent and TEA as an acid binding agent to generate a compound shown in the formula (V); 4) Reacting the compound shown in the formula (V) obtained in the step 3) with NCS and MMA by taking DMF as a solvent and TEA as an acid binding agent to generate a compound shown in the formula (VI), wherein in the step of reaction, H on a benzene ring is not substituted by R1, the obtained product is taken as a main product, H on the benzene ring is substituted by R1, namely a chlorine substitution product is taken as a byproduct, and the byproduct is su