CN108148049B

CN108148049B - Preparation method and application of 5-pyrazole amide compound with triazinone structure

Info

Publication number: CN108148049B
Application number: CN201810067305.2A
Authority: CN
Inventors: 李婉; 杨子辉; 武世杰
Original assignee: Heibei University
Current assignee: Heibei University
Priority date: 2018-01-17
Filing date: 2018-01-17
Publication date: 2020-03-10
Anticipated expiration: 2038-01-17
Also published as: CN108148049A

Abstract

The invention provides 4-chloro-1-alkyl-3-alkyl-N- (3-alkyl-5-oxo-6-phenyl-1, 2, 4-triazine-4- (5H) -yl) -pyrazole-5-formamide shown in a formula (I). Wherein R is¹Is H, C_1‑6A linear or branched alkyl group; r²Is H, halogen, C_1‑6A linear or branched alkyl group; r³Is H, C_1‑6A linear or branched alkyl group; the compound and the pharmaceutically acceptable salt thereof have good killing activity on armyworms at the tested concentration, and can be used as an effective component of an insecticide or a pesticide composition to provide a new choice for the insecticide.

Description

Preparation method and application of 5-pyrazole amide compound with triazinone structure

Technical Field

The invention relates to a preparation method and application of a novel compound, in particular to a 5-pyrazole amide compound containing a triazinone structure and application thereof in preparing pesticides.

Background

N-alkyl-pyrazole-5-carboxamides are newly reported in 90 s as compounds with insecticidal and acaricidal activity, and are concerned by the characteristics of unique action mechanism, safety, high efficiency, no cross resistance and small dosage. Representative species such as tebufenpyrad and tolfenpyrad. The action mechanism of tolfenpyrad is similar to that of tebufenpyrad, and the tolfenpyrad has a broad insecticidal spectrum and has contact killing effect on lepidoptera, hemiptera, thrips and mites.

The triazone is an important structural fragment in pesticide molecules, and the pymetrozine contains a 4-amino 6-methyl-4, 5-dihydro-1, 2, 4-triazine-3-one structure, and is a green pesticide for preventing and controlling cotton and vegetable aphids.

The insecticidal activity of the 5-pyrazole amide compound containing the 4-amino-3-methyl-6-phenyl-1, 2, 4-triazine-5-ketone structure is not reported in the literature.

Disclosure of Invention

The invention aims to provide a preparation method of a 5-pyrazole amide compound containing a triazinone structure and application of the compound as a pesticide.

The 5-pyrazole amide compound containing the triazinone structure has the following structural formula:

wherein R is¹Is H, C_1-6A linear or branched alkyl group;

R²is H, halogen, C_1-6A linear or branched alkyl group;

R³is H, C_1-6A linear or branched alkyl group;

preferably, said R is¹Is C_1-4A linear or branched alkyl group; the R is²Is H, C_1-4A linear or branched alkyl group; the R is³Is H, C_1-4Straight or branched chain alkyl.

More preferably, the compound, or a pharmaceutically acceptable salt thereof, is selected from one of the following compounds:

the preparation method of the 5-pyrazole amide compound containing the triazinone structure provided by the invention comprises the following preparation reactions:

the preparation method of the 5-pyrazole amide compound containing the triazinone structure comprises the following steps:

reaction of 4-amino-3-alkyl-6-phenyl-1, 2, 4-triazin-5- (4H) -one with 4-chloro-1-alkyl-3-alkyl-1H-pyrazole-5-carboxylic acid produces 4-chloro-1-alkyl-3-alkyl-N- (3-alkyl-5-oxo-6-phenyl-1, 2, 4-triazin-4- (5H) -yl) -pyrazole-5-carboxamide.

The preferred molar ratio of the reactants 4-amino-3-alkyl-6-phenyl-1, 2, 4-triazin-5- (4H) -one to 4-chloro-1-alkyl-3-alkyl-1H-pyrazole-5-carboxylic acid is 1: 1.

in some embodiments, the organic solvent is dichloromethane, chloroform, N-dimethylformamide, or tetrahydrofuran.

In some embodiments, the condensing agent is EDCI and HOBt.

In some embodiments, the base is triethylamine

The invention provides an application of 5-pyrazole amide compounds containing triazinone structures or pharmaceutically acceptable salts thereof in preparing insecticide drugs, in particular an application in preparing insecticide drugs.

A further object of the present invention is to provide a pesticidal composition comprising the compound of the present invention or a pharmaceutically acceptable salt thereof as an active ingredient, and one or more pharmaceutically acceptable excipients.

The pesticide composition provided by the invention contains the compound or the pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier or a combination of the compound serving as an active ingredient and a medicinal excipient or a diluent.

The compound and the pharmaceutically acceptable salt thereof have good killing activity on armyworms at the tested concentration, and can be used as an effective component of an insecticide or a pesticide composition to provide a new choice for the insecticide.

Detailed Description

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

The reaction equation of the invention is as follows:

example 1

4-amino-3-alkyl-6-phenyl-1, 2, 4-triazin-5- (4H) -one (4.9mmol), 4-chloro-1-alkyl-3-alkyl-1H-pyrazole-5-carboxylic acid (4.9mmol) were dissolved in DMF and Et was added₃N (0.99g, 9.8mmol), followed by EDCI (5.9mmol), HOBt (5.9mmol) were added and reacted at 50 ℃ for 8 hours,the reaction was complete by TLC. And (3) post-treatment process: removing DMF under reduced pressure, diluting with dichloromethane (50ml), washing with water for three times, washing with brine for one time, drying the dichloromethane layer with anhydrous sodium sulfate, removing dichloromethane under reduced pressure to obtain crude product, and separating with chromatography column [ V ]_{Petroleum ether}∶V_{Ethyl acetate}＝6∶1～4∶1]800mg of white crystals are obtained, m.p.92-95 ℃ with a yield of 44%.¹H NMR(400MHz，CDCl₃)δ：9.02(s，1H，NH)，8.26(d，J＝7.3Hz，2H，C₆H₅)，7.45-7.51(m，3H，C₆H₅)，4.13(s，3H，NHCH₃)，2.70(q，J＝7.6Hz，2H， ₂CHCH₃，pyrazole)，2.64(s，3H，CH₃)，1.28(t，J＝7.6Hz，3H，CH₂ CH ₃，pyrazole)。HRMS(EI)(calcd.m/z)：377.1100(377.1102，M⁺)。

Example 2

And (3) testing the insecticidal activity of the 5-pyrazole amide compound containing the triazinone structure.

Targets were armyworm, alfalfa aphid, cinnabar leaf-house and rice planthopper.

Test agents: example 1 Compounds

Test concentration: the screening concentration was 500 mg/L.

The test method comprises the following steps: the compound of example 1 was formulated with emulsifier (tween-80) and DMF to give a 5.0% EC formulation, which was diluted with distilled water to give a liquid medicine at the desired concentration for measurement. The screening concentration was 500mg/L, and the amount of drug treatment solution was 10 mL. The insecticidal activity of the compound of example 1 against armyworm (Mythima separata) was tested by the leaf dipping method according to "national center for the creation of pesticides standardization" in the south of the country.

Insect sticking: and (3) fully soaking a proper amount of cut corn leaf sections in the prepared liquid medicine, naturally drying in the shade, putting into a culture dish padded with filter paper, inoculating 15 heads/dishes of larvae of 3-year-old midage of armyworms, covering with a mark, and then putting into an observation room for feeding and observing. The results were examined after 3 d. If the body of the insect is touched with a brush pen lightly, no response is regarded as dead insect.

The compound of example 1 has certain inhibitory activity to armyworm at the concentration of 500mg/L, and the inhibition rate is 50%; the inhibition rate to the rice planthopper is 20%, and the compound has an optimization value.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein R is¹Is H, C_1-6A linear or branched alkyl group;

R²is H, halogen, C_1-6A linear or branched alkyl group;

R³is H, C1-6 straight chain or branched chain alkyl.

2. A compound or pharmaceutically acceptable salt thereof according to claim 1, wherein R is¹Is H, C_1-4Straight or branched alkyl, R²Is H, halogen, C_1-4Straight or branched alkyl, R³Is H, C_1-4Straight or branched chain alkyl.

3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, selected from the following compounds:

。

4. a process for preparing 5-pyrazolecarboxamide compounds containing a triazinone structure according to claim 1, which comprises:

taking compounds of formula (II) and formula (III) as raw materials, and synthesizing a target compound (I) through one-step reaction under the conditions of alkali, a condensing agent and an organic solvent; the reaction formula is as follows:

wherein: r¹、R²And R³As defined in claim 1.

5. The method for preparing the 5-pyrazolecarboxamide-based compound containing the triazinone structure according to claim 4, wherein: the feeding molar ratio of the compound of the formula (III) to the compound of the formula (II) is 1: 1.

6. The method for preparing the 5-pyrazolecarboxamide-based compound containing the triazinone structure according to claim 4, wherein: the organic solvent is one or more of dichloromethane, trichloromethane, N, N-dimethylformamide or tetrahydrofuran.

7. The method for preparing the 5-pyrazolecarboxamide-based compound containing the triazinone structure according to claim 4, wherein: the condensing agent is EDCI or HOBt, and the alkali is triethylamine.

8. Use of 5-pyrazolecarboxamide compounds containing a triazinone structure according to any one of claims 1 to 3 for the preparation of insecticides as armyworm-killing insecticides.

9. A pesticidal composition comprising a compound according to any one of claims 1 to 3 or a pharmaceutically acceptable salt thereof as an active ingredient and one or more pharmaceutically acceptable adjuvants, carriers and/or excipients.