CN113620849A - Cyclohexenone compounds and preparation method and application thereof - Google Patents

Abstract

The invention discloses cyclohexenone compounds and a preparation method and application thereof, and belongs to the technical field of pesticides. The technical scheme is as follows: the structural formula of the cyclohexenone compounds is shown as the formula (I):

wherein R is₁Selected from H, methyl, ethyl, propyl or isopropyl; r₂Is selected from

Description

Cyclohexenone compounds and preparation method and application thereof

Technical Field

The invention relates to the technical field of pesticides, and particularly relates to a cyclohexenone compound and a preparation method and application thereof.

Background

The weed control is a crucial link in the process of realizing high-efficiency agriculture. Although the kinds of herbicides on the market are various, the emergence of drug-resistant weeds is more and more common due to the problems of unreasonable use of the herbicide, resistance of the weeds, the service life of the drugs and the economic efficiency of the drugs, and thus scientists are required to continuously research and develop new herbicide varieties with high efficiency, safety, economy and different action mechanisms.

US5563114 discloses the preparation and use as herbicide of the following compound a-1 (numbered 4.20 in the patent):

CN 105884665B discloses a preparation method of cyclohexenone compounds and application of cyclohexenone compounds as herbicides. Compound B-1 (numbered 4 in the patent), the structure is as follows:

however, these known compounds have problems of low herbicidal activity against harmful plants, poor selectivity for crops, narrow herbicidal spectrum, and the like, and are not completely satisfactory. And due to the continuous expansion of the market, the drug resistance of weeds, the service life of the drugs, the economic efficiency of the drugs and the like, and the increasing attention of people on environmental protection, scientists are required to continuously research and develop new herbicide varieties with high efficiency, safety, economy and different action modes.

The cyclohexenone compounds shown in the invention are not reported in a public way.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: overcomes the defects of the prior art, and provides a cyclohexenone compound with high herbicide activity and safety to crops, a preparation method and application thereof.

The technical scheme of the invention is as follows:

in a first aspect, the present invention provides a cyclohexenone compound, which has the following structural formula:

wherein R is₁Selected from H, methyl, ethyl, propyl or isopropyl;

R₂is selected from

Preferably, the compound of formula (I) is selected from:

in a second aspect, the invention further provides a preparation method of the cyclohexenone compound, which comprises the following reaction steps:

R₁selected from H, methyl, ethyl, propyl or isopropyl.

The reaction can be carried out in an inert solvent selected from one or more of acetonitrile, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, tetrahydrofuran, dichloromethane, benzene, toluene, xylene, dichloroethane, and ethyl acetate; an acid such as glacial acetic acid can be added to promote the reaction; a base such as potassium carbonate may also be added to facilitate the reaction.

The preparation of intermediate II can be carried out with reference to the example in US63300281 for the synthesis of clethodim.

The structure and physical properties of some of the compounds of formula (I) are shown in the table below.

TABLE 1

Of partial compounds¹HNMR(CDCl₃300MHz) delta (ppm) data are as follows:

compound 1

¹HNMR(500MHz,Chloroform-d)δ7.66(t,J＝1.0Hz,1H),4.35–4.27(m,4H),3.08–2.97(m,2H),2.88(m,1H),2.80–2.67(m,4H),2.50(m,1H),2.31(m,1H),1.87–1.75(m,1H),1.82–1.72(m,2H),1.71(m,1H),1.61–1.54(m,2H),1.47–1.35(m,6H),1.31(t,J＝6.0Hz,3H),1.17(t,J＝7.0Hz,3H)；

Compound 2

¹HNMR(500MHz,Chloroform-d)δ4.15–4.07(m,4H),3.09–2.97(m,1H),2.94–2.85(m,2H),2.81–2.75(m,2H),2.67–2.59(m,2H),2.55(m,1H),2.47(s,3H),2.22(m,1H),1.82–1.75(m,1H),1.78–1.71(m,2H),1.62(m,1H),1.41–1.36(m,2H),1.33–1.26(m,6H),1.28(t,J＝6.0Hz,3H),1.13(t,J＝7.0Hz,3H)；

Compound 3

¹HNMR(500MHz,Chloroform-d)δ4.22–4.13(m,4H),3.43–3.32(m,5H),3.11(d,J＝6.0Hz,1H),2.99–2.87(m,2H),2.76(m,1H),2.32(m,1H),2.22(m,1H),1.89–1.78(m,1H),1.78–1.71(m,2H),1.66(m,1H),1.55–1.45(m,2H),1.33–1.21(m,12H),1.14(t,J＝7.0Hz,3H)；

Compound 4

¹HNMR(500MHz,Chloroform-d)δ4.34–4.17(m,4H),3.15–3.07(m,5H),2.99(d,J＝6.0Hz,1H),2.91–2.75(m,2H),2.71(m,1H),2.48(m,1H),2.33(m,1H),1.93–1.81(m,5H),1.85–1.77(m,1H),1.69–1.64(m,2H),1.57–1.50(m,6H),1.37(t,J＝6.0Hz,3H),1.24–1.17(m,6H)；

Compound 5

¹HNMR(500MHz,Chloroform-d)δ4.11–4.02(m,4H),3.37(m,1H),3.29-3.23(m,1H),3.14–3.10(m,1H),3.03(m,1H),2.99(d,J＝6.0Hz,1H),2.89–2.81(m,2H),2.72(m,1H),2.61(m,1H),2.31(m,1H),1.92–1.89(m,1H),1.88–1.82(m,2H),1.79(m,1H),1.71–1.64(m,2H),1.65–1.52(m,9H),1.42–1.36(m,6H),1.17(t,J＝7.0Hz,3H)；

Compound 6

¹HNMR(500MHz,Chloroform-d)δ7.75–7.68(m,1H),7.59(t,J＝1.0Hz,1H),7.44–7.38(m,2H),4.95(m,1H),4.41(m,1H),4.33(m,1H),2.93(m,1H),2.87(m,1H),2.81–2.75(m,4H),2.55(m,1H),2.31(m,1H),1.81(m,1H),1.58(m,1H),1.49(d,J＝6.2Hz,3H),1.33(d,J＝5.7Hz,3H),1.26(t,J＝6.0Hz,3H)；

Compound 7

¹HNMR(500MHz,Chloroform-d)δ7.41–7.35(m,1H),7.21–7.04(m,2H),4.67(m,1H),4.21–4.15(m,2H),2.91–2.83(m,2H),2.89(d,J＝6.0Hz,1H),2.75(d,J＝1.0Hz,1H),2.67–2.61(m,1H),2.55–2.48(m,1H),2.46(m,1H),2.33(s,3H)2.23(m,1H),1.74(m,1H),1.66(m,1H),1.52(d,J＝6.2Hz,3H),1.39(d,J＝5.7Hz,3H),1.33(t,J＝6.0Hz,3H)；

Compound 8

¹HNMR(500MHz,Chloroform-d)δ7.55–7.47(m,1H),7.44–7.38(m,2H),4.88(m,1H),4.51–4.46(m,2H),2.85(m,4H),2.66(d,J＝6.0Hz,1H),2.55–2.47(m,2H),2.41(m,1H),2.32(m,1H),2.26(m,1H),1.78(m,1H),1.71(m,1H),1.55(d,J＝6.2Hz,3H),1.27(d,J＝5.7Hz,3H),1.42–1.36(m,6H)；

Compound 9

¹HNMR(500MHz,Chloroform-d)δ7.80–7.77(m,1H),7.43–7.32(m,2H),4.63(m,1H),4.14–4.03(m,2H),2.92(m,1H),2.83–2.68(m,3H),2.79(d,J＝6.0Hz,1H),2.69–2.62(m,2H),2.53(m,1H),2.33(m,1H),2.21(m,1H),1.85–1.73(m,3H),1.63(m,1H),1.55(d,J＝6.2Hz,3H),1.33(d,J＝5.7Hz,3H),1.26(t,J＝6.0Hz,3H),1.17(t,J＝7.4Hz,3H)；

Compound 10

¹HNMR(500MHz,Chloroform-d)δ7.70–7.64(m,1H),7.47–7.41(m,2H),4.55(m,1H),4.22–4.13(m,2H),3.13(m,1H),2.99(m,1H),2.86(m,1H),2.79(d,J＝6.0Hz,1H),2.69–2.61(m,2H),2.58(m,1H),2.44(dd,J＝12.4,7.1Hz,1H),2.17(dq,J＝14.3,7.1Hz,1H),1.68(ddd,J＝13.4,7.3,6.2Hz,1H),1.59(m,1H),1.54(d,J＝6.2Hz,3H),1.36–1.27(m,12H)。

In organic molecules, increasing the length of the carbon chain results in large differences in electronegativity, spatial structure, etc. of the entire molecule, and thus the conductance of the entire molecule in organisms such as plants is greatly different. The conductive properties of bioactive molecules are unpredictable and require a great deal of creative work to obtain.

Compared with the disclosed compounds A-1 and B-1, the compound of the general formula (I) not only has high biological activity and wider weed control spectrum, but also has unexpected crop safety, especially very safe to crops such as rice, rape and the like.

In a third aspect, the invention also provides the application of the cyclohexenone compounds in herbicide compositions.

Preferably, the weight percentage of the cyclohexenone compounds in the herbicide composition is 0.1-99%.

A further embodiment of the present invention is a method of controlling weeds which comprises applying a herbicidally effective amount of the herbicidal composition to the weeds or to the locus where the weeds grow or to the surface of the growth medium thereof. In general, effective amounts of from 10 grams per hectare to 5000 grams per hectare are preferred, with effective amounts of from 30 grams per hectare to 500 grams per hectare being preferred. Also, one or more other classes of herbicides can be added to the herbicidal compositions of the present invention, thereby yielding additional advantages and effects.

Several methods for preparing the compounds of the present invention are described in detail in the examples below. The starting materials are commercially available or can be prepared by methods known in the literature or as shown in detail. It will be appreciated by those skilled in the art that other synthetic routes may also be utilized to synthesize the compounds of the present invention. Although specific starting materials and conditions for the synthetic route are described below, they can be readily substituted with other similar starting materials and conditions, and variations or modifications of the preparation process of the present invention, such as various isomers of the compounds, are included in the scope of the present invention. In addition, the preparation methods described below may be further modified in accordance with the present disclosure using conventional chemical methods well known to those skilled in the art. For example, protecting the appropriate groups during the reaction, and the like.

The compound of the invention not only has high herbicidal activity, but also is safe to crops, provides a new raw material for herbicides, and is suitable for wide popularization and application.

Detailed Description

Synthesis example 1: synthesis of Compound 3

Step 1:

methyl 3-hydroxy-2-methylpropionate (16.0g,100mmol), phthalimide (16.3g,100mmol) and triphenylphosphine (28.8g,110mmol) were added to a 500mL three-necked flask, and then dissolved in tetrahydrofuran (200mL) with stirring, and the temperature was reduced to 0 ℃ or lower. A solution of DEAD (19.2g,110mmol) in tetrahydrofuran was added dropwise, and after the addition was completed, the temperature was naturally raised to room temperature, followed by stirring overnight. TLC monitored reaction completion, water (200mL) was added and extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated, and chromatographed on silica gel to give a white solid (22.7g,75mmol) in 75% yield.

Step 2:

the product of the previous step (22.7g,75mmol) was added to a 500mL three-necked flask, dissolved in methanol (200mL), and 80% hydrazine hydrate (24g,375mmol) was added and stirred overnight. TLC was carried out until the reaction was complete, and the solid was removed by suction filtration, methanol was removed by rotary drying, and the residue was dissolved in ethyl acetate, washed with water, dried over anhydrous sodium sulfate, filtered, concentrated, and subjected to silica gel column chromatography to obtain a syrup (10.7g,62mmol) in 82% yield.

And step 3:

in a 100mL single neck flask was added the compound of step 2 (3.5g,20mmol), sodium bicarbonate (5.1g,60mmol), methanol (50mL), the compound butyrylcyclohexanone (5.4g,20mmol, prepared as described in document U.S. Pat. No. 6,63300281) and stirred overnight. TLC monitoring, until the material disappeared, suction filtration to remove solid, spin-dry methanol, ethyl acetate dissolved, water washed, anhydrous sodium sulfate drying, filtration, concentration, silica gel column chromatography to obtain the target product (7.8g,18.5mmol), yield 93%.

Other compounds of the invention can be prepared by the methods described above.

Bioassay example 2: determination of herbicidal Activity and crop safety

Evaluation of biological Activity:

the activity level criteria for harmful plant destruction (i.e. growth control rate) are as follows:

and 5, stage: the growth control rate is more than 85 percent;

4, level: the growth control rate is more than or equal to 60 percent and less than 85 percent;

and 3, level: the growth control rate is more than or equal to 40% and less than 60%;

and 2, stage: the growth control rate is more than or equal to 20% and less than 40%;

level 1: the growth control rate is more than or equal to 5% and less than 20%;

level 0: the growth control rate is less than 5%.

The growth control rate is the fresh weight control rate.

Sowing quantitative weed seeds (barnyard grass, semen Euphorbiae Lathyridis) and crop seeds (rice) in 8cm diameter plastic pots filled with soil, covering soil 0.5-2cm after sowing, compacting, spraying water, and culturing in greenhouse by conventional method. So that the plant can grow in a good greenhouse environment. When weeds and rice grow to 2-3 leaf stages, selecting test materials with uniform growth for spraying the stem leaves after seedlings; the compound of the invention to be tested is dissolved by acetone respectively, then a proper amount of Tween 80 is added, and the solution is diluted into solution with a certain concentration by a certain amount of water and is sprayed on plants by a spray tower. After the application, the culture is carried out in a greenhouse for 21 days, the experimental effect is counted after 21 days, and the treatment of spraying the Tween 80 aqueous solution with the same concentration without the medicament is taken as a blank control. The compound doses used were 20, 10, 5 g/ha, and each treatment was repeated three times, and the average was taken. And the compound A-1 and the compound B-1 are used as control agents, and the herbicidal activity and safety are measured in parallel. Representative data are presented in table 2.

TABLE 2 herbicidal Activity and crop safety of different compounds (21d)

Indoor activity experiments show that the compounds with the formula (I) numbers 1-10 of the invention show high biological activity on grassy weeds which are difficult to control in three paddy fields of barnyard grass, moleplant seed and digitaria sanguinalis at three doses of 5, 10 and 20 g/ha 21 days after application, and are obviously higher than the control compound A-1 and the control compound B-1, especially the compound 3, the compound 4, the compound 8 and the compound 9. Meanwhile, the safety of the compound numbers 1-10 of the formula (I) to crop rice at three doses of 5, 10 and 20 g/ha is also obvious due to the control compound A-1 and the control compound B-1. The compound of formula (I) has high weeding bioactivity, wide weeding spectrum and good selectivity to crops such as rice and the like, and has good development and application prospects.

This is because, in organic compounds, compound molecules having different chemical structures have large differences in physical and chemical properties such as steric structure, active group, electronegativity, charge distribution, hydrophobicity, and the like. There are great differences in the biological activity, the mechanism of herbicidal action, and the absorption and in vivo conductance properties of compounds of different structures on plant surfaces. The difference of physical and chemical properties such as spatial structure, active group, electronegativity, charge distribution and hydrophobicity is the reason that the compound of formula (I) is superior to the control compound A-1 and the control compound B-1 in the aspects of safety to rice, herbicidal activity to barnyard grass, large crabgrass and moleplant seed and the like.

Claims (5)

1. The cyclohexenone compound is characterized in that the structural formula is as follows:

wherein R is₁Selected from H, methyl, ethyl, propyl or isopropyl;

R₂is selected from

2. Cyclohexenone compound according to claim 1, wherein the compound of formula (I) is selected from:

3. the process for producing the cyclohexenone compounds according to claim 1 or 2, wherein the reaction steps are as follows:

R₁selected from H, methyl, ethyl, propyl or isopropyl.

4. Use of the cyclohexenone compounds as claimed in claim 1 or 2 in a herbicidal composition.

5. The use as claimed in claim 4, wherein the weight percentage of the cyclohexenone compounds in the herbicidal composition is from 0.1 to 99%.