阅读说明：本技术 一种喹啉4-位羟基吡啶甲酸酯类化合物及其防治水稻稻瘟病菌的用途 (Quinoline 4-hydroxypyridine formate compound and application thereof in preventing and treating rice blast germs ) 是由 杨子辉 杨树林 刘畅 白玉凤 于 2020-05-29 设计创作，主要内容包括：本发明公开一种喹啉4-位羟基吡啶甲酸酯类化合物,所述化合物具有如下结构：<Image he="242" wi="700" file="DDA0002516540070000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>其中R＝F,Cl,OCH<Sub>3</Sub>。具体制备步骤如下,6-三氟甲基-4-喹啉醇和7,8-二甲氧基-4-喹啉醇分别与2-取代吡啶-3-甲酸在催化剂,缩合剂和有机溶剂条件下反应制备一种喹啉4-位羟基吡啶甲酸酯化合物(I)和(II)。所述化合物(I)和(II)对水稻稻瘟病菌有较好的防效。化合物(I)和(II)的制备方法操作简单,收率较高,产物性质稳定。(The invention discloses a quinoline 4-hydroxypicolinate compound, which has the following structure: wherein R ═ F, Cl, OCH 3 . The specific preparation steps are as follows, 6-trifluoromethyl-4-quinolinol and 7, 8-dimethoxy-4-quinolinol react with 2-substituted pyridine-3-formic acid respectively under the conditions of a catalyst, a condensing agent and an organic solvent to prepare quinoline 4-position hydroxypicolinate compounds (I) and (II). The compounds (I) and (II) have better control effect on rice blast germs. The preparation method of the compounds (I) and (II) has the advantages of simple operation, high yield and stable product property.)

1. A quinoline 4-position hydroxypyridine formate compound and an application thereof in preventing and treating rice blast germs are disclosed, wherein the quinoline 4-position hydroxypyridine formate compound has the following structural formula:

wherein R ═ F, Cl, OCH₃。

2. The compound of quinoline 4-hydroxypicolinate according to claim 1, wherein 6-trifluoromethyl-4-quinolinol and 7, 8-dimethoxy-4-quinolinol are reacted with 2-substituted pyridine-3-carboxylic acid under the conditions of catalyst, condensing agent and organic solvent to prepare the quinoline 4-hydroxypicolinate compounds (I) and (II), respectively.

3. The preparation method of the quinoline 4-hydroxypicolinate compound according to claim 2, wherein the feeding molar ratio of the reactants 6-trifluoromethyl-4-quinolinol and 7, 8-dimethoxy-4-quinolinol to the 2-substituted picolinic acid is 1.0-1.2:1, preferably 1: 1.1.

4. The method for preparing quinoline 4-hydroxypicolinate compounds according to claim 2, wherein the organic solvent is one or more of dichloromethane, tetrahydrofuran and chloroform.

5. The method for preparing quinoline 4-hydroxypicolinate compounds according to claim 2, wherein the catalyst is 4-Dimethylaminopyridine (DMAP).

6. The method for preparing quinoline 4-hydroxypicolinate compounds according to claim 2, wherein the condensing agent is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI).

7. Use of a compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for controlling Pyricularia oryzae.

8. A pesticide composition, which is characterized by comprising the compound or pharmaceutically acceptable salt thereof as an effective component according to any one of claims 1 to 7 and one or more pharmaceutically acceptable auxiliary materials.

Technical Field

The invention relates to a new compound and application thereof, in particular to a quinoline 4-hydroxypicolinate compound and application thereof in preventing and treating rice blast germs.

Background

The quinoline compounds have wide biological activity, such as insecticidal activity, bactericidal activity and herbicidal activity. In the field of fungicides, two varieties of phenoxyquinoline and tebufloquin have been marketed. Has gradually become a research hotspot of various large pesticide companies at home and abroad.

The first variety of quinoline bactericides, namely, the quinoxyquinoline, has been developed by Yinong Dow, has the drug effect by disturbing spore germination, is mainly used for strawberry powdery mildew and wheat powdery mildew, has been applied to crops such as vegetables, wheat and the like in a large area since the 20 th century and the 70 th era, and has the characteristics of systemic property and protection.

The Tebufloquin bactericide developed and marketed by Mingzhi fruit-control company in 2012 is a new variety with a fluorine-containing quinoline structure, has good control effect on powdery mildew and rice blast, and has the characteristics of low production cost and low dosage. In China, some researchers have designed and synthesized derivatives of Tebufloquin, according to the existing literature reports, Heptafluoropropyl is introduced by the chemical research institute in Zhejiang province, a plurality of series of quinoline compounds containing Heptafluoroisopropyl are synthesized, and a candidate bactericide ZJ5337 (benzyl carbonate-2, 3, 8-trimethyl-6-Heptafluoroisopropyl-4-quinoline ester) with better activity than Tebufloquin is screened out from the derivatives, has the inhibition rate of 80% on rice blast and powdery mildew at the concentration of 50mg/L-100mg/L, and has the characteristics of safety to rice and rain wash resistance; compound HNPC-A15269 developed by Hunan chemical research institute for inhibiting EC in living bodies of wheat powdery mildew₅₀1.48mg/L, is better than tebufloquin and is safe to crops.

A series of compounds, 6- (tert-butyl) -8-fluoro-2, 3-dimethyl quinoline ester, such as a compound 1A, are designed and synthesized by Chenlong and the like, and have better prevention and treatment activity on rice blast; the compound 1B reported by Liu Hainan has good bactericidal activity on rice blast fungi at the concentration of 100 mg/L; compound 1C synthesized by chaperone or the like; has excellent control effect on wheat powdery mildew.

In the subject, a salesman takes a commercial variety of tebufloquin as a lead compound and introduces a picolinate group into a 4-quinol mother nucleus, and the synthesis of the compounds shown in the formula I and the formula II and the activity of preventing and treating rice blast germs are not researched and developed.

Disclosure of Invention

One of the objects of the invention is achieved by: a quinoline 4-position hydroxypicolinate compound is provided, and has the following structural formula:

wherein R ═ F, Cl, OCH₃。

The second object of the present invention, namely the selected compounds, is the following:

the third purpose of the invention is realized by the following steps: a preparation method of quinoline 4-position hydroxypicolinate comprises the following steps of reacting 6-trifluoromethyl-4-quinolinol and 7, 8-dimethoxy-4-quinolinol with 2-substituted pyridine-3-formic acid respectively in the presence of a catalyst, a condensing agent and an organic solvent to prepare quinoline 4-position hydroxypicolinate compounds (I) and (II).

The invention aims to provide a preparation method of quinoline 4-position hydroxypicolinate, which is characterized by comprising the following preparation reactions:

wherein R ═ F, Cl, OCH₃。

Preferably, the feeding molar ratio of the reactant 6-trifluoromethyl-4-quinalditol or 7, 8-dimethoxy-4-quinalditol to the 2-substituted picolinic acid is 1.0-1.2:1, preferably 1: 1.1.

Preferably, the reaction solvent is one or more of dichloromethane, tetrahydrofuran and chloroform.

Preferably, the catalyst is 4-Dimethylaminopyridine (DMAP).

Preferably, the condensing agent is 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI).

The fourth purpose of the invention is realized by the following steps: the application of the formula (I) and the formula (II) provided by the invention can effectively prevent and treat the rice blast fungus plant fungal diseases under a lower dose, and can be used alone or combined with other compounds with bactericidal activity.

The fifth purpose of the invention is realized by the following steps:

a pesticide composition takes quinoline 4-position hydroxypicolinate shown in formula (I) and formula (II) or pharmaceutically acceptable salt thereof as an active component, and an agriculturally acceptable carrier.

The quinoline 4-hydroxypicolinate prepared by the invention has bactericidal activity on the common rice blast of paddy fields in agriculture, can be used independently, and can also be used in combination with other active substances with bactericidal activity, so that the comprehensive performance of the product is improved; because the bactericide contains pyridine-3-formic acid group, namely nicotinic acid group, the bactericide has low toxicity to beneficial organisms, is easy to degrade and has good environmental compatibility, provides a new choice for creating new varieties of bactericides and has potential industrial application prospect.

Detailed Description

The following examples are intended to illustrate the invention without further limiting it.