WO2014172924A1

WO2014172924A1 - Quinoline derivative and application thereof

Info

Publication number: WO2014172924A1
Application number: PCT/CN2013/075323
Authority: WO
Inventors: 唐剑峰; 王如军; 吴雪; 潘光明; 刘杰; 李文宏
Original assignee: 山东省联合农药工业有限公司
Priority date: 2013-04-22
Filing date: 2013-05-08
Publication date: 2014-10-30
Also published as: CN103214461B; CN103214461A

Abstract

The present invention provides a quinoline derivative and an application thereof. The quinoline derivative has a structure shown in a general formula A. The quinoline derivative or an agriculture and garden acceptable acid addition salt thereof can be used as an active component of insecticides in the agriculture and the garden to kill insects of lepidoptera, homoptera, coleoptera and orthoptera, does not generate cross resistance, and also has stronger killing activity to pests which already have pesticide resistance.

Description

Quinoline derivative and use thereof

The invention belongs to the technical field of insecticides, and in particular relates to a quinoline derivative and its use.

Background technique

In modern agriculture and garden production, some insect species are difficult to control, and some insect species have significantly increased resistance. The existing insecticides have greatly reduced the rate of pest control, and developed a new type of agriculture and garden with excellent insecticidal activity. Insecticides are an inevitable measure to solve the current low rate of pesticide control.

Quinoline is chemically active and can react with other substances. The resulting quinoline derivative has a broad spectrum of insecticidal activity and high biological activity.

Summary of the invention

The object of the present invention is to provide a quinoline derivative and its use in view of the problems in the prior art mentioned above. In order to achieve the above object, the present invention adopts the following technical scheme: a quinoline derivative having a structure as shown in Formula A

among them:

Represents a hydrogen atom or C0OR ₇ , wherein R ₇ represents a ₄ fluorenyl group;

R ₂ does not. Bu ₄ base;

R _{3 3⁄4} C _t — ₄ yard base;

R ₄ and R ₅ each independently represent a hydrogen atom, a halogen atom, a d- _{4 a} group, a d- ₄ alkyl group optionally substituted by a halogen atom, a d- ₄ alkoxy group, a d- ₄ carbonyl group, wherein R ₄ , R ₅ does not indicate a hydrogen atom;

R ₆ represents a hydrogen atom or a halogen atom.

A quinoline derivative of the invention, wherein:

Represents C0OR ₇ , wherein R ₇ represents d- ₄ alkyl;

No. Bu ₄ base;

table. Bu ₄ base;

R ₄ and R ₅ each independently represent a hydrogen atom optionally substituted by a halogen atom, and a d- ₄ courtyard group, wherein R ₄ and R ₅ do not simultaneously represent a hydrogen atom;

R ₆ represents a hydrogen atom or a halogen atom.

A quinoline derivative of the invention wherein:

Represents C0OR" where R ₇ represents CH ₃ ;

Indicates CH ₃ ;

R ₃ table CH ₃ ;

R ₄ represents CH ₃ ;

Represents a hydrogen atom;

R ₆ represents a hydrogen atom.

A quinoline derivative of the present invention, wherein:

Represents C0OR ₇ , where R ₇ represents C ₂ H ₅ ;

Table is not C ₂ H ₅ ;

Indicates CH ₃ ; Table hydrogen atom;

Indicates CH ₃ ;

R ₆ represents a hydrogen atom.

Use of a quinoline derivative of the present invention or an agriculturally and garden-acceptable acid addition salt thereof for the preparation of an insecticide.

A quinoline derivative of the invention for killing Lepidoptera, Homoptera, Coleoptera, Orthoptera insects.

The quinoline derivative of the invention has a pyridine ring and a quinoline ring structure, and is used for the insecticide with high systemicity and good plant permeability, and can quickly and effectively kill agricultural and garden pests and diseases, insecticidal spectrum. Wide, environmentally compatible.

A quinoline derivative of the present invention or an agriculturally and pharmaceutically acceptable acid addition salt thereof as an active ingredient of an insecticide inhibits respiratory metabolism of a pest by inhibiting electron transfer of mitochondria between pest cytochrome b and cl At the same time, it can also act on the acetylcholine enzyme receptor, interfere with the nervous system of the pest, and kill and control the target organism through contact and killing, and the killing rate can reach 100%.

A quinoline derivative of the present invention or an agriculturally and horticulturally acceptable acid addition salt thereof can be used for killing larvae and adults of Lepidoptera, Coleoptera, Homoptera, Orthoptera, and does not produce cross-resistance Sexually, it also has strong killing activity against pests that have developed resistance.

detailed description

The structure shown in A:

among them:

R ₂ does not. Bu ₄ base;

R ₃ does not. Bu ₄ base;

R _4, _{R. 5} each independently represent a hydrogen atom, a halogen atom, firing d- _4-yl, optionally substituted by a halogen atom d- ₄ embankment, alkoxy, d- _4-ylcarbonyl hospital, wherein R _4, R ₅ does not indicate a hydrogen atom at the same time;

Represents a hydrogen atom or a halogen atom.

The preferred solution is:

A quinoline derivative of the invention, wherein:

Represents C0OR ₇ , wherein R ₇ represents d- ₄ alkyl;

No. Bu ₄ base;

table. Bu ₄ base;

Represents a hydrogen atom or a halogen atom.

A quinoline derivative of the invention wherein:

Represents C0OR" where R ₇ represents CH ₃ ;

Indicates CH ₃ ;

R ₃ table CH ₃ ;

R ₄ represents CH ₃ ;

Represents a hydrogen atom;

R ₆ represents a hydrogen atom. A quinoline derivative of the invention wherein:

Represents C0OR ₇ , where R ₇ represents C ₂ ;

Table is not C ₂ H ₅ ;

R ₃ represents CH ₃ ;

Represents a hydrogen atom;

R ₅ represents CH ₃ ;

Represents a hydrogen atom.

Use of a quinoline derivative of the present invention or an agriculturally and garden-acceptable acid addition salt thereof for the preparation of an insecticide. The insecticide may be combined as an active ingredient with an agriculturally acceptable carrier, and the active ingredient of the insecticide is present in an amount of from 0.5 to 90% by weight. The dosage form of the insecticide may be a dry powder, a visible powder, an emulsifiable concentrate, a microemulsion, a paste, a granule, a solution, a suspending agent, and prepared according to a known method. The agriculturally and garden-acceptable acid addition salts thereof may be hydrochlorides, phosphates, nitrate sulfates or acetates.

Insects.

9

CZCS.0/CT0ZN3/X3d

£Z£SLO/£lOZSi3/13d

6

01

CZCS.0/CT0ZN3/X3d

The synthesis method of a quinoline derivative of the present invention is as follows:

1 compound X phenol is dissolved in a solvent and refluxed under basic conditions to give intermediate I 3 ^C , "

Shen Yuyu I .

2 Intermediate I and compound Y are refluxed under basic conditions to give intermediate II

? V, 0 8 3⁄4w W 3⁄4 ,

, Ί ⁺ α ' ^≠ί , ^Ί : R into ⁱ , o _s

Recorded in the middle of it-f !1 .

3 After dissolving the intermediate II in the solvent, placing it in an autoclave, adding 10% palladium carbon, and introducing a certain pressure of hydrogen,

Middle body

4 intermediate III and the disubstituted propylenedione acid ethyl ester compound are dissolved in a solvent, and refluxed under the catalysis of pity acid or p-toluenesulfonic acid to obtain a reaction product of the reaction step;

According to the structural formula A:

When Ι^=Η, the reaction product is the quinoline derivative of the structure of the invention having the structure shown in the formula ,, and the synthesis reaction ends; when R^COOR, the reaction product is the intermediate IV, and the synthesis reaction continues: 0: o

c., f r. 丫⁰丫1⁄4,

T, 0

In the middle of the foot

3s;=«t, is 衍生 derivative A;: When R^COOR, the synthesis method of a quinoline derivative of the invention still has the fifth step:

5 Intermediate IV is dissolved in a solvent, an acid binding agent is added, and the chloroformate is reacted at 10 ° C or lower to obtain a compound A, which is bound.

'钟!A

In the second step 1-5,

Express C

, R ₅ each independently represent a hydrogen atom, a halogen atom, alkyl with ₄ optionally substituted by a halogen atom hospital group i,

C oxy, d- ₄ carbonyl, wherein R ₄ , R ₅ do not denote a hydrogen atom;

R ₆ represents a hydrogen atom or a halogen atom;

R ₇ does not.卜₄焼基;

The solvent described in the step 1-5 may be an alcohol solvent or hydrazine, hydrazine-dimethylformamide; and the base used in the basic conditions described in the steps 1 and 2 may be an organic base or an inorganic base.

A quinoline derivative having the general formula of the present invention and its use, according to the specific compounds in the table, can have the following specific synthesis examples:

Example 1

Intermediate I

The specific synthetic steps of (R ₆ =H) are as follows:

Dissolve 1 mol of hydroquinone in 5 L of ethanol, add 1 mol of potassium carbonate, reflux for 8 h, distill off ethanol at -0.095 kPa, 80 ° C under reduced pressure, then cool to room temperature, add 1 L of N, N-dimethyl The amide is then added to 1 mol of 2-chloro-5-trifluoromethylpyridine, and the temperature is raised, and the reaction is carried out in the range of 50-55 ° C for 8 h. Then, the reaction mixture is poured into 5 L of water, stirred, and the precipitated crystals are filtered and dried to obtain 200 g of intermediate I in a yield of 78.4%.

Elemental analysis is: C, 56.48; H, 3.16; F, 22.33; N, 5.49; 0, 12.54.

m/z: 255.05 (100.0%), 256.05 (13,4%).

Example 2 Synthesis of intermediate π from intermediate I:

The specific synthetic steps are as follows:

0.05 mol of the intermediate I was dissolved in 100 ml of N,N-dimethylformamide, and 0.05 mol of potassium hydroxide powder and 0.05 mol of 3-methyl-4-chloronitrobenzene were successively added, and the temperature was refluxed for 8 h to be reduced. After normal temperature, the reaction solution was poured into 1 L of water, extracted with 100 ml of chloroform for 30 min, and chloroform was distilled off at -0.095 kPa, and chloroform was distilled off at 100 ° C to obtain a viscous oily substance, which was chromatographed with ethyl acetate / petroleum ether = 8:2. The column was separated to give 9.4 g of Intermediate II.

Elemental analysis: C, 53.73; H, 2.85; C1, 8.35; F, 13.42; N, 6.60; O, 15.07.

m/z: 424.04 (100.0%), 426.04 (32.1%), 425.05 (20.8%), 427.04 (6.8%), 426.05 (2.9%) Example 3

Synthesis of intermediate III from intermediate II:

The specific synthetic steps are as follows:

Dissolve 0.05 mol of the intermediate II in 500 ml of ethanol, place it in an autoclave, replace it with N _{2 for} 3 times, add lg 10% palladium carbon, and pass H l"22 kg/cm ^{2 at} 40-45 ° C until the pressure is not After further dropping, the reaction was carried out for 8 hours, and the mixture was vented, and the filtrate was filtered off, and the mixture was filtered under reduced pressure of -0.095 kPa at 100 ° C to obtain an oily substance, which was separated with ethyl acetate / petroleum ether = 8:2 to obtain 8.5 g of intermediate. III, the yield was 45.5%.

Elemental analysis: C, 64.17; H, 4.58; F, 15.22; N, 7.48; 0, 8.55.

m/z: 374.12 (100.0%), 375.13 (21.9%), 376.13 (2.7%)

Example 4

Synthesis of intermediate IV from intermediate III:

R ₃ =CH ₃ , R ₄ =CH ₃ ,

The specific synthetic steps for R ₅ =H, R ₆ =H) are as follows:

0.05 mol of intermediate III, 0.05 mol of ethyl 2-methyl-3-oxobutanoate, 250 ml of toluene, and 0.5 g of p-toluenesulfonic acid were sequentially added to the reaction vessel, and refluxed for 12 hours, and then added to the reaction vessel. 100 ml, stirred for 30 min, layered, -0.095 kPa, and the solvent was evaporated under reduced pressure at 100 ° C, and separated with ethyl acetate / petroleum ether = 6:4 to give 18.7 g of Intermediate IV. 85%.

Elemental analysis: C, 65.45; H, 4.35; F, 12.94; N, 6.36; 0, 10.90.

m/z: 440.13 (100.0%), 441.14 (26.3%), 442.14 (4.1%)

Example 5

ø

Synthesis of Compound A from Intermediate w: ',^(...,In,,,,, (!^=(:0(» ₇ ,1 ₂ =(3⁄4,1^=(3⁄4

The specific synthetic steps for R ₄ =C , R ₅ =H, R ₆ =H, R ₇ =CH ₃ ) are as follows:

O.Olmol intermediate IV was dissolved in 500 ml of chloroform, 0.012 mol of triethylamine was added, the temperature was lowered to below 10 ° C, and O.Olmol methyl chloroformate was added for 24 h. After completion of the reaction, water was added to 100 ml, stirred for 30 min, and layered. -0.095kPa, 100°C The solvent was evaporated under reduced pressure and purified with ethyl acetate / petroleum ether = 7:3 to give 3 g of Compound A, yield: 60.24% Elemental analysis: C, 62.65; H, 4.25; F, 11.43; N, 5.62; 0, 16.05.

m/z: 498.14 (100.0%), 499.14 (29.1%), 500.15 (3.9%), 500.14 (1.2%).

Biological example

Biological testing of insecticides prepared by using a quinoline derivative of the formula A having the structure of the formula A or an agriculturally and pharmaceutically acceptable acid addition salt thereof as an active ingredient, and existing Insecticides for comparison:

Example 1, apple leaf curler (Lepidoptera) test

Solvent: 7 parts by weight of dimethyl sulfoxide;

Emulsifier: 2 parts by weight of decyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 2, compound 5, trichlorfon;

The above components are mixed in a weight ratio and diluted to a desired concentration. In accordance with national standards - "Indoor Biometric Test Guidelines"

The results in the table indicate that the insecticides prepared by using Compound 2 and Compound 5 as active ingredients have comparable activities, and the control effect is significantly higher than that of trichlorfon.

Example 2, Helicoverpa armigera (Lepidoptera) test

Solvent: 7 parts by weight of dimethyl sulfoxide;

Emulsifier: 2 parts by weight of decyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 7, compound 8, compound 10,

The above components are mixed in a weight ratio and diluted to a desired concentration. According to the national standard - "Indoor Bioassay Test Guidelines", cotton bollworms were immersed in each agent for treatment by dipworm and leaf dip method. The results are as follows:

The results in the table show that the insecticides prepared by using Compound 7, Compound 8, and Compound 10 as active ingredients are significantly more effective than beta-cypermethrin.

Example 3, Plutella xylostella (Lepidoptera) Test

Solvent: 7 parts by weight of dimethyl sulfoxide;

Emulsifier: 2 parts by weight of decyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 11, compound 12, compound 14, avermectin;

The above components are mixed in a weight ratio and diluted to a desired concentration. In accordance with the national standard - "Indoor Bioassay Test Guidelines", Plutella xylostella was immersed in each agent for treatment. The results are as follows:

The results in the table show that the insecticides prepared by using Compound 11, Compound 12, and Compound 14 as active ingredients have a significantly higher control effect than avermectin.

Example 4, Green-spotted cockroach (Homoptera) test

Solvent: 7 parts by weight of dimethyl sulfoxide; Emulsifier: 2 parts by weight of decyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 16 hydrochloride, malathion;

The above components are mixed in a weight ratio and diluted to a desired concentration. In accordance with the national standard - "Indoor Bioassay Test Guidelines", the green blind cockroaches were immersed in each agent for treatment by the immersion method and the leaf leaching method. The results are as follows:

The results in the table indicate that the insecticide prepared by using the hydrochloride salt of Compound 16 as the active ingredient has a significantly higher control effect than malathion.

Example 5, Cotton leafhopper (Homoptera) test

Solvent: 7 parts by weight of dimethyl sulfoxide;

Emulsifier: 2 parts by weight of decyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 17, compound 20, bifenthrin;

The above components are mixed in a weight ratio and diluted to a desired concentration. According to the national standard - "Indoor Bioassay Test Guidelines", the larvae of cotton leafhopper were immersed in each medicament for treatment. The results are as follows:

The results in the table show that the control effect of pesticides prepared with compound 17 and compound 20 as active ingredients is significantly higher than that of biphenyl. Example 6, straw tube (Homoptera) test

Solvent: 8.5 parts of acetone;

Emulsifier: 0.5 parts by weight of decyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 22, compound 23, compound 24, imidacloprid;

The above components are mixed in a weight ratio and diluted to a desired concentration. In accordance with the national standard - "Indoor Bioassay Test Guidelines" dip method, the larvae of the wheat larvae were immersed in each agent for treatment. The results are as follows:

The results in the table show that the insecticides prepared by using Compound 22, Compound 23 and Compound 24 as active ingredients have significantly higher control effects than imidacloprid.

Example 7, Brown planthopper (Homoptera) test

Solvent: 8.5 parts of acetone;

Emulsifier: 0.5 parts by weight of decyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 30, compound 31, imidacloprid;

The above components are mixed in a weight ratio and diluted to a desired concentration. In accordance with the national standard - "Indoor Bioassay Test Guidelines" dipworm method, the brown planthopper larvae were immersed in each agent for treatment. The results are as follows:

The results in the table show that the control effect of pesticides prepared with compound 30 and compound 31 as active ingredients is significantly higher than that of imidacloprid. Example 8, Golden Needle (Coleoptera) Test

Solvent 8.5 parts of acetone;

Emulsifier: 0.5 part by weight of t alkyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 33, compound 34, compound 35, butyl thiocarbamate;

The above components are mixed at a weight I: ratio and diluted to the desired concentration. Oral bioassay was used and the results are as follows:

The results in the table show that the insecticides prepared by using Compound 33, Compound 34 and Compound 35 as active ingredients have a significantly higher control effect than those of butyl thiocarbamate.

Example 9, Mung bean (Coleoptera) test

Solvent: 8.5 parts of acetone;

Emulsifier: 0.5 part by weight of t-mercaptoaryl polyglycol ether;

Active ingredient: 1 part by weight I: compound 40, compound 44, fenthion;

The above components are mixed by weight: ratio and diluted to the desired concentration. Oral bioassay was used and the results are as follows:

The results in the table show that the control effect of the insecticide prepared by using Compound 40 and Compound 44 as active ingredients is significantly higher than that of chlorpyrifos.

Example 10, Yellow-striped Jumping (Coleoptera) Test

Solvent: 8.5 parts of acetone;

Emulsifier: 0.5 parts by weight of alkyl aryl polyglycol ether;

Active ingredient: 1 part by weight of compound 46, compound 47, compound 48, chlorpyrifos;

The results in the table show that the insecticides prepared by using Compound 46, Compound 47, and Compound 48 as active ingredients have a significantly higher control effect than chlorpyrifos.

Example 11, Chinese rice blast (Orthoptera) test

Solvent: 9 parts of dimethyl sulfoxide;

Active ingredient: 1 part by weight of compound 51, compound 52, compound 53, flubenzuron;

The above components are mixed in a weight ratio and diluted to a desired concentration. Oral bioassay was used and the results are as follows:

The results in a table show that the insecticidal control effect prepared by using compound 51, compound 52 and compound 53 as active ingredients is significantly higher than that of flubendiamide. Example 12, 嵝蛄 (Orthoptera) test

Solvent: 9 parts of dimethyl sulfoxide;

Active ingredient: 1 part by weight of compound 60, chlorpyrifos;

The above components are mixed in a weight ratio and diluted to a desired concentration. Using the soil mixed feeding method, the results are as follows:

The results in the table show that the insecticidal control effect prepared by using compound 60 as the active ingredient is significantly higher than that of chlorpyrifos.

Claims

A quinoline derivative characterized by having a structure as shown in Formula A:

Formula A

Two of them

It represents a hydrogen atom or C0OR _7, wherein R ₇ represents alkyl C _H;

Table is not C Bu ₄ yard base;

Table C- ₄ yard base;

R _4, _{R. 5} each independently represent a hydrogen atom, a halogen atom, D- ₄ alkyl, optionally substituted by a halogen atom D- ₄ alkyl group, 4 embankment group, d- ^ carbonyl group, wherein R _4, R ₅ does not indicate a hydrogen atom at the same time;

Represents a hydrogen atom or a halogen atom.

2. A quinoline derivative according to claim 1 wherein:

Represents C0OR ₇ , where R ₇ represents d_ ₄ fluorenyl;

R _z 3⁄4 Js. [— ₄焼 base;

Represents C _w alkyl;

R ₄ and R ₅ each independently represent a hydrogen atom optionally substituted by a halogen atom, and a d ₄ alkyl group, wherein R ₄ and R ₅ do not simultaneously represent a hydrogen atom;

Represents a hydrogen atom or a halogen atom.

3. A quinoline derivative according to claim 1 wherein:

Represents C0OR ₇ , where R ₇ represents C;

R ₂ represents CH ₃ ;

Indicates CH ₃ ;

Indicates CH _3;

Represents a hydrogen atom:

Represents a hydrogen atom.

4. The two quinoline derivatives according to claim 1, wherein:

Represents C0OR ₇ , where R ₇ represents C ₂ H ₅ ;

Table ^ C ₂ H ₅ ;

Table CH ₃ ;

Represents a hydrogen atom;

Table does not CH ₃ ;

Represents a hydrogen atom.

Use of a quinoline derivative or an agriculturally and pharmaceutically acceptable acid addition salt thereof according to claim 1 or 2 for the preparation of an insecticide.

6. A quinoline derivative according to claim 1 for use in the killing of Lepidoptera, Homoptera, Coleoptera, Orthoptera.