CN116283802A - A herbicidal compound containing (R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl structure and its preparation and application - Google Patents

Abstract

(R) -2- [4- (6-chloroquinolin-2-yloxy) phenoxy group]Propionyl structural compound, its structural general formula (I) is:

Description

A herbicidal compound containing a (R)-2-[4-(6-chloroquinoline-2-yloxy)phenoxy]propionyl structure and its preparation and application

Technical Field

The invention belongs to the field of pesticide chemistry and discloses a compound containing a (R)-2-[4-(6-chloroquinoline-2-yloxy)phenoxy]propionyl structure, a preparation method thereof and application as a herbicide.

Background Art

Weeds refer to plants that grow in places that are harmful to human survival and activities. They compete with crops for light, nutrients and water, invade part of the above-ground and underground space, hinder field ventilation and light transmission, seriously affect crop yield and quality, and are one of the biological disasters that threaten agricultural production.

Chemical herbicides have good weed control effects and can kill most common annual and perennial weeds. They have the advantages of thorough weed control, time-saving, labor-saving, and low cost, and have become the main means of weed control. However, in recent years, with the succession of weed populations and the emergence and rapid development of their resistance to chemical pesticides, as well as people's increased awareness of protecting the ecological environment, new green, safe, and unique herbicide compounds have become an urgent need for agricultural production.

The (R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl structure is one of the main active structures of aryloxyphenoxypropionic acid herbicides. Aryloxyphenoxypropionic acid herbicides are mainly used to control grass weeds. Their mechanism of action is mainly to inhibit the activity of acetyl-CoA carboxylase in grass plants, thereby inhibiting the synthesis of fatty acids. Fatty acids have important physiological functions in plants. They are the basic structural components of triglycerides, which are the main energy storage and energy supply substances. The phospholipids converted from them are components of cell membranes. Fatty acids can also be converted into hormone substances that regulate metabolism. Due to its high herbicidal activity, low toxicity and good selectivity, researchers have modified and transformed the structure of aryloxyphenoxypropionate esters and developed a series of highly active varieties. Currently, the commercial herbicide varieties based on the aryloxyphenoxypropionate structure include quizalofop-p-butyl, oxadiazol-butyl, thiazolyl-butyl, clodinafop-butyl, cyhalofop-butyl, high-efficiency fluazifop-p-butyl, fluazifop-p-methyl, etc. Patents EP 0023785A2, US4528025A and CN102718722A1 report that certain aryloxyphenoxycarboxylic acid ester compounds have good herbicidal activity.

Summary of the invention

In order to overcome the above-mentioned problems of the prior art, the present invention introduces a series of functional groups into the (R)-2-[4-(6-chloroquinoline-2-yloxy)phenoxy]propionyl structure to increase the target sites of the herbicidal action of the new compound. With the increasingly prominent problem of resistant weeds, new varieties of herbicides with novel structures and unique mechanisms of action have become an urgent demand of the market. Therefore, the development of herbicidal compounds containing multifunctional groups using the (R)-2-[4-(6-chloroquinoline-2-yloxy)phenoxy]propionyl structure as the active leading group has good application prospects.

Specifically, the first aspect of the present invention is to provide a herbicidal compound containing a (R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl structure, the general structural formula of which is shown in formula (I):

In formula (I), (CH2)n represents a straight chain or branched alkyl group having 2 to 6 carbon atoms;

X represents NH, O or S atom;

R represents 2-chloro-5-methyl-thiazole or substituted aryl;

The hydrogen on the substituted aryl benzene ring may be substituted by one or more of the following groups: halogen, nitro, sulfonic acid, alkyl (including branched alkyl), halogen-substituted alkyl.

The preferred R is the following structure:

The second aspect of the present invention is to provide a method for preparing the herbicidal compound represented by formula (I) according to the first aspect of the present invention, comprising the following steps:

1) R-Cl or R-Br reacts with diamine, alcoholamine or aminothiol in a solvent with a base as a catalyst by heating to produce a nucleophilic substitution reaction, and the reaction product is purified by desolventizing to obtain an intermediate C;

2) The intermediate C solution dissolved in an organic solvent is added dropwise to 2(R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl chloride (II), and in the presence of an acid-binding agent, an esterification or amidation reaction is performed to obtain the compound represented by formula (I).

Its chemical reaction process:

The R-Cl or R-Br may be: 2-chloro(bromo)-5-tert-butyl-1,3-dinitrobenzene, 4-chloro(bromo)-3,5-dinitrobenzotrifluoride, 2-chloro(bromo)-5-tert-butyl-1,3-dinitrobenzene, 2,4-dinitrobenzenesulfonyl chloride (bromine), 2-chloro(bromo)-5-chloromethylthiazole;

In the diamine, alcoholamine or aminothiol, (CH ₂ ) _n represents a straight chain or branched alkyl group having 2 to 6 carbon atoms;

The esterification or amidation reaction solvent may be one or more of dichloromethane, dichloroethane, tetrahydrofuran, N,N-dimethylformamide, N-methylpyrrolidone or dimethyl sulfoxide, preferably tetrahydrofuran;

The acid-binding agent in the esterification or amidation reaction can be one of pyridine, triethylamine, tri-n-propylamine, tri-n-butylamine, N,N-diisopropylethylamine, 4-dimethylaminopyridine and tetramethylethylenediamine, preferably triethylamine.

In the above preparation method, the molar ratio of compound (II), intermediate C and acid binding agent in the esterification or amidation reaction is 1:(0.8-2):(0-2), and the optimal molar ratio is 1:1.1:1.1;

The esterification or amidation reaction temperature is 0-100°C, and the optimal reaction temperature is 25°C-40°C;

The esterification or amidation reaction time is 1 to 12 hours, and the optimal reaction time is 2 to 8 hours.

The third aspect of the present invention also provides the use of the compound represented by formula (I) as a herbicide.

The technical effects achieved by the present invention are:

1. The compound containing the (R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl structure provided by the present invention has a novel structure and many advantages such as high herbicidal activity;

2. The preparation method provided by the present invention is simple and has a short reaction process.

DETAILED DESCRIPTION

The technical content of the present invention is further described below in conjunction with specific examples, but it is not intended to limit the present invention. The experimental methods used in the following examples are all conventional methods unless otherwise specified.

Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources. Table 1 shows the structural formula of the intermediate C in the examples.

Table 1 Structural formula of intermediate C

Example 1

(1) Add 7.5 mmol of ethylenediamine, 5.5 mmol of triethylamine and 10 mL of methanol to a 50 mL reaction bottle. Slowly drop 5 mmol of 3,5-dinitro-4-chlorotrifluorotoluene and 15 mL of methanol and stir for 4 hours. After the reaction is completed, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter and desolventize to obtain intermediate C1 as a yellow solid.

The synthesis methods of intermediates C2-C5, C16-C20, C31-C35, and C46-C50 are the same as above.

(2) Add 2.2 mmol of intermediate C1 and 10 mL of tetrahydrofuran to a 50 mL reaction bottle, stir until completely dissolved, then add 3.0 mmol of triethylamine as an acid binding agent. Use an ice bath to lower the temperature of the reaction system to 0-4°C, slowly drop 5 mL of tetrahydrofuran containing 2.0 mmol of 2(R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl chloride (II), heat to 40°C and react for 2 hours. After the reaction is completed, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter, and distill under reduced pressure to obtain product Ⅰ-1 as a yellow solid. The reaction yield is 73.7%, and the product content is 98.4%.

The synthesis methods of products Ⅰ-2~Ⅰ-5, Ⅰ-16~Ⅰ-20, Ⅰ-31~Ⅰ-35, Ⅰ-46~Ⅰ-50 are the same as above.

Example 2

(1) Add 6 mmol of 2-hydroxyethylamine, 5.5 mmol of triethylamine and 10 mL of methanol to a 50 mL reaction bottle. Slowly drop 5 mmol of 3,5-dinitro-4-chlorotrifluorotoluene and 15 mL of methanol and stir for 4 hours. After the reaction is completed, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter and desolventize by vacuum distillation to obtain intermediate C6 as a yellow solid.

The synthesis methods of intermediates C7-10, C21-C25, C36-C40, and C51-C55 are the same as above.

(3) Add 2.2 mmol of intermediate C6 and 10 mL of tetrahydrofuran to a 50 mL reaction bottle, stir until completely dissolved, then add 3.0 mmol of triethylamine as an acid binding agent. Use an ice bath to lower the temperature of the reaction system to 0-4°C, slowly drop 5 mL of tetrahydrofuran containing 2.0 mmol of 2(R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl chloride (II), and react for 6 hours. After the reaction, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter, and distill under reduced pressure to obtain product Ⅰ-6 as a yellow solid. The reaction yield is 72.1%, and the product content is 98.8%.

The synthesis methods of products Ⅰ-7~Ⅰ-10, Ⅰ-21~Ⅰ-25, Ⅰ-36~Ⅰ-40, Ⅰ-51~Ⅰ-55 are the same as above.

Example 3

(1) Add 5.5 mmol of 2-mercaptoethylamine, 5.5 mmol of triethylamine and 10 mL of methanol to a 50 mL reaction bottle. Slowly drop 5 mmol of 3,5-dinitro-4-chlorotrifluorotoluene and 15 mL of methanol and stir for 6 hours. After the reaction is completed, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter and desolventize to obtain intermediate C11 as a yellow solid.

The synthesis methods of intermediates C12-15, C26-C30, C41-C45, and C56-C60 are the same as above.

(2) Add 2.2 mmol of intermediate C11 and 10 mL of tetrahydrofuran to a 50 mL reaction bottle, stir until completely dissolved, then add 3.0 mmol of triethylamine as an acid binding agent. Use an ice bath to lower the temperature of the reaction system to 0-4°C, slowly drop 5 mL of tetrahydrofuran containing 2.0 mmol of 2(R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl chloride (II), and react for 8 hours. After the reaction, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter, and distill under reduced pressure to obtain product Ⅰ-11 as a yellow solid. The reaction yield is 70.5%, and the product content is 97.2%.

The synthesis methods of products Ⅰ-12~Ⅰ-15, Ⅰ-26~Ⅰ-30, Ⅰ-41~Ⅰ-45, Ⅰ-56~Ⅰ-60 are the same as above.

Example 4

(1) Add 7.5 mmol of ethylenediamine, 5.5 mmol of triethylamine and 10 mL of tetrahydrofuran to a 50 mL reaction bottle. Lower the temperature of the reaction system to 0-4°C in an ice bath, slowly drop 5 mmol of 2,4-dinitrobenzenesulfonyl chloride and 15 mL of tetrahydrofuran, and stir for 4 hours. After the reaction is completed, pour the reactants into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter, and evaporate under reduced pressure to obtain intermediate C61 as a yellow solid.

The synthesis method of intermediates C62~C65 is the same as above.

(2) Add 2.2 mmol of intermediate C61 and 10 mL of tetrahydrofuran to a 50 mL reaction bottle, stir until completely dissolved, then add 3.0 mmol of triethylamine as an acid binding agent. Use an ice bath to lower the temperature of the reaction system to 0-4°C, slowly drop 5 mL of tetrahydrofuran containing 2.0 mmol of 2(R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl chloride (II), and react for 2 hours. After the reaction, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter, and distill under reduced pressure to obtain product Ⅰ-61 as a yellow solid. The reaction yield is 71.1%, and the product content is 97.3%.

The synthesis method of products Ⅰ-62~Ⅰ-65 is the same as above.

Example 5

(1) Add 6 mmol of 2-hydroxyethylamine, 5.5 mmol of triethylamine and 10 mL of tetrahydrofuran to a 50 mL reaction bottle. Slowly drop 5 mmol of 2,4-dinitrobenzenesulfonyl chloride and 15 mL of tetrahydrofuran and stir for 4 hours. After the reaction is completed, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter and evaporate under reduced pressure to obtain intermediate C66 as a yellow solid.

The synthesis method of intermediates C67~C70 is the same as above.

(3) Add 2.2 mmol of intermediate C6 and 10 mL of tetrahydrofuran to a 50 mL reaction bottle, stir until completely dissolved, then add 3.0 mmol of triethylamine as an acid binding agent. Use an ice bath to lower the temperature of the reaction system to 0-4°C, slowly drop 5 mL of tetrahydrofuran containing 2.0 mmol of 2(R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl chloride (II), and react for 6 hours. After the reaction, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter, and distill under reduced pressure to obtain product Ⅰ-66 as a yellow solid. The reaction yield is 72.5%, and the product content is 98.8%.

The synthesis method of products Ⅰ-67~Ⅰ-70 is the same as above.

Example 6

(1) Add 5.5 mmol of 2-mercaptoethylamine, 5.5 mmol of triethylamine and 10 mL of tetrahydrofuran to a 50 mL reaction bottle. Slowly drop 5 mmol of 2,4-dinitrobenzenesulfonyl chloride and 15 mL of tetrahydrofuran and stir for 6 hours. After the reaction is completed, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter and evaporate under reduced pressure to obtain intermediate C71 as a yellow solid.

The synthesis method of intermediates C72~75 is the same as above.

(2) Add 2.2 mmol of intermediate C71 and 10 mL of tetrahydrofuran to a 50 mL reaction bottle, stir until completely dissolved, then add 3.0 mmol of triethylamine as an acid binding agent. Use an ice bath to lower the temperature of the reaction system to 0-4°C, slowly drop 5 mL of tetrahydrofuran containing 2.0 mmol of 2(R)-2-[4-(6-chloroquinolin-2-yloxy)phenoxy]propionyl chloride (II), and react for 8 hours. After the reaction, pour the reactant into water, extract with ethyl acetate, wash with water 3 times, dry the organic phase with anhydrous magnesium sulfate, filter, and distill under reduced pressure to obtain product Ⅰ-71 as a yellow solid. The reaction yield is 73.5%, and the product content is 97.8%.

The synthesis method of products Ⅰ-72~Ⅰ-75 is the same as above.

The appearance and yield of the product (I) of the above example are listed in Table 2.

Table 2 Appearance and yield of product (I)

Example 7

Determination of herbicidal activity: The herbicidal activity of the compounds of the present invention was evaluated by potted stem and leaf treatment experiment.

Seeds of barnyard grass and foxtail grass were sown in plastic pots with a diameter of 9 cm respectively. The experimental soil was a mixture of vermiculite, nutrient soil and humus soil. After sowing, the soil was covered with 0.5 cm and cultured in a greenhouse according to conventional methods after watering. During the period, the seedlings were thinned twice to ensure that there were 12-15 barnyard grasses in each pot. The weeds were applied when they had two leaves and one heart leaf. The compounds of the present invention were dissolved in methanol and 0.5% Tween 80 was added and stirred evenly. After being diluted with water to a solution of a certain concentration, the application amount per pot was 2 mL. The experiment was repeated 3 times. After application, the fresh weight inhibition rate of the compound on barnyard grass was investigated in the greenhouse for one week to calculate the calculation formula:

Fresh weight inhibition rate (100%) = [(fresh weight of control weeds - fresh weight of treated weeds) / fresh weight of control weeds] × 100%

For comparison, a comparative experiment was conducted using Quizalofop-Ph-ethyl, a commercial herbicide based on the aryloxyphenoxypropionate structure.

The statistical results of fresh weight inhibition rate are shown in Table 3.

Table 3 Statistical results of the fresh weight inhibition rate of compounds on barnyard grass and foxtail grass

Note: ++++++, 100%. +++++, ≥90%. ++++, ≥80%. +++, ≥70%. ++, ≥60%. +, ≥50%. --, <50%

From the statistical results of the fresh weight inhibition rate of the compounds on barnyard grass and foxtail grass shown in Table 3 above, it can be seen that the fresh weight inhibition rate of the compounds of the present invention on barnyard grass and foxtail grass is above 70%, and many of them reach 90%, indicating that the compounds of the present invention have the advantage of high herbicidal activity.

Those skilled in the art will readily appreciate other embodiments of the present disclosure after considering the specification and practicing the disclosure disclosed herein. This application is intended to cover any modification, use or adaptation of the present disclosure, which follows the general principles of the present disclosure and includes common knowledge or customary techniques in the art that are not disclosed in the present disclosure. The specification and examples are intended to be exemplary only, and the true scope and spirit of the present disclosure are indicated by the claims of the present application.

Claims (9)

1. A weeding compound containing (R) -2- [4- (6-chloroquinolin-2-yloxy) phenoxy ] propionyl structure has a structural formula shown in formula (I):

in the formula (I), (CH) ₂ ) n represents a linear or branched alkyl group having 2 to 6 carbon atoms;

x represents NH, O or S atom;

r represents 2-chloro-5-methyl-thiazole or substituted aryl;

the hydrogen on the substituted aryl benzene ring may be substituted with one or more of the following groups: halogen, nitro, sulfonic, alkyl containing branches, halogen substituted alkyl.

2. The compound of formula (i) according to claim 1, wherein R is of the structure:

3. a process for the preparation of a compound of formula (i) as claimed in claim 1, comprising the steps of:

step 1): R-Cl or R-Br and diamine, alcohol amine or amino mercaptan are heated in a solvent by taking alkali as a catalyst to carry out nucleophilic substitution reaction, and a reaction product is desolventized and purified to obtain an intermediate C;

step 2): the intermediate C solution dissolved in an organic solvent is added into 2 (R) -2- [4- (6-chloroquinolin-2-yloxy) phenoxy ] propionyl chloride (II) in a dropwise manner, and the compound shown in the formula (I) is obtained through esterification or amidation reaction in the presence of an acid binding agent.

4. The process according to claim 3, wherein R-Cl or R-Br in step 1 is: 2-chloro (bromo) -5-tert-butyl-1, 3-dinitrobenzene, 4-chloro (bromo) -3, 5-dinitrobenzotrifluoride, 2-chloro (bromo) -5-tert-butyl-1, 3-dinitrobenzene, 2, 4-dinitrobenzenesulfonyl chloride (bromo), 2-chloro (bromo) -5-chloromethylthiazole;

in the diamine, alcohol amine or aminothiol, (CH) ₂ ) _n Represents a linear or branched alkyl group having 2 to 6 carbon atoms.

5. The preparation method according to claim 3, wherein the esterification or amidation reaction solvent in the step 2 is one or more of dichloromethane, dichloroethane, tetrahydrofuran, N-dimethylformamide, N-methylpyrrolidone and dimethyl sulfoxide;

the acid binding agent in the esterification or amidation reaction is one of pyridine, triethylamine, tri-N-propylamine, tri-N-butylamine, N-diisopropylethylamine, 4-dimethylaminopyridine and tetramethyl ethylenediamine.

6. The process according to claim 5, wherein the esterification or amidation reaction solvent is tetrahydrofuran;

the acid binding agent in the esterification or amidation reaction is triethylamine.

7. The preparation method according to claim 2, wherein the molar ratio of the compound (II), the intermediate C and the acid-binding agent in the esterification or amidation reaction in the step 2 is 1 (0.8-2): 0-2;

the esterification or amidation reaction temperature is 0-100 ℃;

the esterification or amidation reaction time is 1-12 hours.

8. The process according to claim 7, wherein the molar ratio of compound (II), intermediate C and acid-binding agent in the esterification or amidation reaction in step 2 is 1:1.1:1.1;

acid binding agent in the esterification or amidation reaction, wherein the temperature of the esterification or amidation reaction is 25-40 ℃;

the esterification or amidation reaction time is 2-8 hours.

9. The use of a compound of formula (i) as claimed in claim 1 as herbicide.