Heterocarboxylic acid dimer as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of pesticides, and discloses a heterocarboxylic acid dimer as well as a preparation method and application thereof. Herbicides such as 2, 4-dichlorphenoxyacetic acid, 2-methyl-4-chlorophenoxyacetic acid and fluroxypyr acting on a TIR1 target point and herbicides such as dicamba and halauralid acting on an AFB5 target point are connected through a connecting arm containing groups such as O, S and N, so that the heterologous carboxylic acid dimer is constructed. The herbicidal activity and crop safety determination results show that compared with the single use or mixed use of the parent compound, the synthesized heterocarboxylic acid dimer has higher herbicidal activity and better crop safety. In addition, the preparation method of the heterologous carboxylic acid dimer is safe, simple and feasible.

Description

Technical Field

[0001] The invention relates to the technical field of pesticides, and in particular to a heterologous carboxylic acid dimer and a preparation method and application thereof. Background Art

[0002] The selectivity of pesticide application can cause weeds and other harmful organisms to develop resistance. Once weeds develop resistance, their sensitivity to a certain type or class of pesticides, or even multiple types of pesticides, will decrease, further leading to reduced or even complete loss of control effects, thus causing significant losses in agricultural production. Therefore, it is necessary to continuously develop new agricultural biological active compounds with high-efficiency herbicidal activity and resistance risks to meet the needs of weed resistance management and agricultural production. In addition, as people pay more and more attention to their health and environmental protection, higher standards are also being put forward for pesticides that directly affect the safety of agricultural products and the environment. It is urgent to develop new varieties of pesticides such as high-efficiency, low-toxic, and environmentally friendly herbicides, insecticides, and fungicides.

[0003] Heterologous carboxylic acid dimers are a new type of compound synthesized using heterologous oligomerization technology. At present, the use of homologous oligomerization synthesis method for compound creation has been widely used in the fields of pesticides, medicine, materials, etc. CN105254546A discloses homologous oligomers of substituted phenoxyacetic acid herbicides; CN1849888A, CN1986522A, CN1995025A, CN101007799A, CN1995023A, CN1986533A respectively disclose homologous oligomers of insecticides such as avermectin, fipronil, carbamates, pyrimidine salicylic acid herbicides and triazoles. Although homologous carboxylic acid dimers show excellent biological activity, they are essentially superpositions of carboxylic acid compounds with the same mechanism of action, and the improvement of their biological activity is also due to the increase in the relative content of active carboxylic acids, which is not good for improving the safety of the agent. Therefore, how to further improve the biological activity of homologous carboxylic acid dimers and their safety to crops is an urgent problem that needs to be solved. Summary of the invention

[0004] The purpose of the present invention is to provide a heterologous carboxylic acid dimer and a preparation method and application thereof, so as to solve the above-mentioned problems existing in the existing homologous oligomer herbicides.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a heterologous carboxylic acid dimer, the structural formula of the heterologous carboxylic acid dimer is as follows:

[0007]

[0008] Among them, R1 Selected from one of the following groups:

[0009]

[0010] R 2 Selected from one of the following groups:

[0011]

[0012] X 1 , X 2 is independently one of O, S, and NH;

[0013] Y is selected from phenyl, pyridyl, piperidyl, pyrimidinyl, tetrahydropyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, tetrahydrothienyl, furanyl, pyrazolyl, oxazolyl, isoxazolyl, quinolyl, isoquinolyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cyclopent ... One of pentenyl, cyclopentadienyl, cyclobutanyl and cyclopropanyl; C2-C12 alkyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl; C2-C12 alkenyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl; one of C2-C12 alkynyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl.

[0014] Preferably, in the structural formula of the heterologous carboxylic acid dimer, R 1 Selected from one of the following groups:

[0015]

[0016] R 2 Selected from one of the following groups:

[0017]

[0018] X 1 , X 2 independently O or S;

[0019] Y is selected from one of C2-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl and phenyl.

[0020] The present invention also provides a method for preparing a heterologous carboxylic acid dimer, which is selected from one of method A, method B, and method C;

[0021] The method A comprises the following steps:

[0022] Will contain R 1 The acyl chloride and the connecting arm are reacted in the presence of a base and a solvent to obtain an intermediate; 2 The acyl chloride and the intermediate react in the presence of a base and a solvent to obtain a heterologous carboxylic acid dimer;

[0023] The method B comprises the following steps:

[0024] Will contain R 1 The carboxylic acid and the connecting arm are subjected to condensation reaction in the presence of a condensing agent, a base and a solvent to obtain an intermediate; 2 The carboxylic acid and the intermediate are subjected to a condensation reaction in the presence of a condensation agent, a base and a solvent to obtain a heterologous carboxylic acid dimer;

[0025] The method C comprises the following steps:

[0026] Will contain R 1 The acyl chloride and the connecting arm are reacted in the presence of a base and a solvent to obtain an intermediate; 2 The carboxylic acid and the intermediate are subjected to a condensation reaction in the presence of a condensation agent, a base and a solvent to obtain a heterologous carboxylic acid dimer;

[0027] Or will contain R 1 The carboxylic acid and the connecting arm are subjected to condensation reaction in the presence of a condensing agent, a base and a solvent to obtain an intermediate; 2 The acyl chloride and the intermediate are reacted in the presence of a base and a solvent to obtain a heterologous carboxylic acid dimer.

[0028] Preferably, the R 1 The structure of the carboxylic acid is The R-containing 2 The structure of the carboxylic acid is The structure of the connecting arm is

[0029] Preferably, the R 1 The preparation method of the acyl chloride is as follows: 1 The carboxylic acid and the chlorine-containing compound are reacted in the presence of a catalyst and a solvent to obtain a compound containing R 1 of acyl chloride;

[0030] The R 2 The preparation method of the acyl chloride is as follows: 2 The carboxylic acid and the chlorine-containing compound are reacted in the presence of a catalyst and a solvent to obtain a compound containing R2 of acyl chloride.

[0031] Preferably, the chlorine-containing compound is one of thionyl chloride, oxalyl chloride and triphosgene.

[0032] Preferably, in method A and method C, the R 1 The molar ratio of the acyl chloride, the base, and the connecting arm is independently 1:1 to 5:1 to 4; the R 2 The molar ratio of the acid chloride, the base and the intermediate is independently 1:1-5:1-4.

[0033] Preferably, in method B and method C, the R 1 The molar ratio of the carboxylic acid, condensing agent, base and connecting arm is independently 1:1.1-5:1.1-5:1.1-4; the R-containing 2 The molar ratio of the carboxylic acid, the condensing agent, the base and the intermediate is independently 1:1 to 5:1 to 5:1 to 4.

[0034] Preferably, in method A and method C, the reaction temperature is independently 25°C or 66-153°C reflux; the reaction time is independently 2-12h;

[0035] In method B and method C, the temperature of the condensation reaction is independently 25° C. or 66-153° C. reflux; and the time of the condensation reaction is independently 2-12 hours.

[0036] The present invention also provides an application of a heterologous carboxylic acid dimer in controlling weeds.

[0037] It can be seen from the above technical solution that compared with the prior art, the present invention has the following beneficial effects:

[0038] The present invention connects herbicides such as 2,4-dichlorophenoxyacetic acid, 2-methyl-4-chlorophenoxyacetic acid, clofopyralid, etc., which act on the TIR1 target, and herbicides such as dicamba and clofopyralid, which act on the AFB5 target, through a connecting arm containing groups such as O, S, and N, thereby constructing a heterologous carboxylic acid dimer. The results of herbicidal activity and crop safety determination show that compared with the parent compound used alone or in combination, the synthesized heterologous carboxylic acid dimer has higher herbicidal activity and better crop safety. In addition, the preparation method of the heterologous carboxylic acid dimer of the present invention is safe, simple and feasible. DETAILED DESCRIPTION

[0039] The present invention provides a heterologous carboxylic acid dimer, the structural formula of the heterologous carboxylic acid dimer is as follows:

[0040]

[0041] Among them, R 1Selected from one of the following groups:

[0042]

[0043] R 2 Selected from one of the following groups:

[0044]

[0045] X 1 , X 2 is independently one of O, S, and NH;

[0046] Y is selected from phenyl, pyridyl, piperidyl, pyrimidinyl, tetrahydropyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, tetrahydrothienyl, furanyl, pyrazolyl, oxazolyl, isoxazolyl, quinolyl, isoquinolyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cyclopent ... One of pentenyl, cyclopentadienyl, cyclobutanyl and cyclopropanyl; C2-C12 alkyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl; C2-C12 alkenyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl; one of C2-C12 alkynyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl.

[0047] In the present invention, in the structural formula of the heterologous carboxylic acid dimer, R 1 Preferably it is one of the following groups:

[0048]

[0049] More preferably, it is one of the following groups:

[0050] In the present invention, in the structural formula of the heterologous carboxylic acid dimer, R 2 Preferably it is one of the following groups:

[0051] More preferably, it is one of the following groups:

[0052] In the present invention, in the structural formula of the heterologous carboxylic acid dimer, X 1 , X 2 Preferably, they are independently O or S, more preferably O.

[0053] In the present invention, in the structural formula of the heterologous carboxylic acid dimer, Y is preferably one of C2-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, and phenyl, and more preferably one of C2-C12 alkyl, C2 alkenyl, C4 alkenyl, and phenyl.

[0054] The present invention also provides a method for preparing a heterologous carboxylic acid dimer, which is selected from one of method A, method B, and method C;

[0055] The method A comprises the following steps:

[0056] Will contain R 1 The acyl chloride and the connecting arm are reacted in the presence of a base and a solvent to obtain an intermediate; 2 The acyl chloride and the intermediate react in the presence of a base and a solvent to obtain a heterologous carboxylic acid dimer;

[0057] The method B comprises the following steps:

[0058] Will contain R 1 The carboxylic acid and the connecting arm are subjected to condensation reaction in the presence of a condensing agent, a base and a solvent to obtain an intermediate; 2 The carboxylic acid and the intermediate are subjected to a condensation reaction in the presence of a condensation agent, a base and a solvent to obtain a heterologous carboxylic acid dimer;

[0059] The method C comprises the following steps:

[0060] Will contain R 1 The acyl chloride and the connecting arm are reacted in the presence of a base and a solvent to obtain an intermediate; 2 The carboxylic acid and the intermediate are subjected to a condensation reaction in the presence of a condensation agent, a base and a solvent to obtain a heterologous carboxylic acid dimer;

[0061] Or will contain R 1 The carboxylic acid and the connecting arm are subjected to condensation reaction in the presence of a condensing agent, a base and a solvent to obtain an intermediate; 2 The acyl chloride and the intermediate are reacted in the presence of a base and a solvent to obtain a heterologous carboxylic acid dimer.

[0062] In the present invention, the R 1 The structure of the carboxylic acid is preferably The R 2 The structure of the carboxylic acid is preferably The structure of the connecting arm is preferably

[0063] In the present invention, the R 1 The preparation method of the acyl chloride is as follows: 1 The carboxylic acid and the chlorine-containing compound are reacted in the presence of a catalyst and a solvent to obtain a compound containing R 1 of acyl chloride;

[0064] The R 2 The preparation method of the acyl chloride is as follows: 2 The carboxylic acid and the chlorine-containing compound are reacted in the presence of a catalyst and a solvent to obtain a compound containing R 2 of acyl chloride.

[0065] In the present invention, R 1 Acid chloride, containing R 2 In the method for preparing the acyl chloride, the chlorine-containing compound is preferably one of thionyl chloride, oxalyl chloride and triphosgene, more preferably oxalyl chloride or triphosgene, more preferably oxalyl chloride; the catalyst is preferably N,N-dimethylformamide; the amount of the chlorine-containing compound relative to the amount of R 1 Carboxylic acid or R 2 The carboxylic acid is in excess; the amount of the catalyst is preferably a catalytic amount; the reaction temperature is preferably 25°C or 66-153°C reflux, more preferably 25°C; the reaction time is preferably 2-12h, more preferably 3-8h, more preferably 4h.

[0066] In the present invention, in method A, method B and method C, the solvent is independently preferably one of tetrahydrofuran, acetonitrile, acetone, butanone, cyclohexane, dimethylformamide, dichloromethane, chloroform, dioxane, methylnaphthalene, dimethyl sulfoxide, N-methylpyrrolidone, N-formylmorpholine and N-acetylmorpholine, further preferably one of tetrahydrofuran, dichloromethane, chloroform and N-methylpyrrolidone, and more preferably dichloromethane.

[0067] In the present invention, in method A, method B and method C, the base is independently preferably one of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, triethylamine, tri-n-propylamine, N,N-diisopropylethylamine, pyridine and 4-dimethylaminopyridine, further preferably one of potassium carbonate, triethylamine, pyridine and 4-dimethylaminopyridine, and more preferably triethylamine.

[0068] In the present invention, in method B and method C, the condensing agent is preferably one or more of dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), more preferably DCC or EDCI, and more preferably EDCI.

[0069] In the present invention, in method A and method C, the R 1 The molar ratio of the acyl chloride, the base, and the linker arm is independently preferably 1:1-5:1-4, more preferably 1:1.1-2:1.1-1.5, and more preferably 1:1.2:1.2; the R-containing 2 The molar ratio of the acid chloride, the base, and the intermediate is independently preferably 1:1 to 5:1 to 4, more preferably 1:1 to 2:1 to 2, and even more preferably 1:1:1.

[0070] In the present invention, in method B and method C, the R 1 The molar ratio of the carboxylic acid, condensing agent, base and connecting arm is preferably 1:1.1-5:1.1-5:1.1-4 independently, more preferably 1:1.1-1.5:1.1-2:1.1-2, more preferably 1:1.2:1.2:1.2; the R-containing 2 The molar ratio of the carboxylic acid, the condensing agent, the base and the intermediate is independently preferably 1:1 to 5:1 to 5:1 to 4, more preferably 1:1 to 3:1 to 3:1 to 2, and more preferably 1:1:1:1.

[0071] In the present invention, in method A and method C, the reaction temperature is independently preferably 25°C or 66-153°C reflux, more preferably 25°C; the reaction time is independently preferably 2-12h, further preferably 3-5h, more preferably 4h.

[0072] In the present invention, in method B and method C, the temperature of the condensation reaction is independently preferably 25°C or 66-153°C reflux, more preferably 25°C; the time of the condensation reaction is independently preferably 2-12h, further preferably 3-5h, more preferably 4h.

[0073] The present invention also provides an application of a heterologous carboxylic acid dimer in controlling weeds.

[0074] In the present invention, the weeds are preferably weeds in orchards, non-arable land, dry fields and paddy fields; the weeds are preferably one or more of broadleaf weeds, grass weeds and sedge weeds; the broadleaf weeds preferably include velvetleaf, Amaranthus retroflexus, Chenopodium album, Commelina, Kochia scoparia, Echinochloa serrata, Polygonum aviculare and the like; the grass weeds preferably include barnyard grass, crabgrass, Setaria viridis and the like; the sedge weeds preferably include firefly rush, Scirpus sylvestris, Cyperus rotundus, and cow hair felt and the like.

[0075] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0076] The heterologous carboxylic acid dimer of the present invention includes but is not limited to one of the following structures, as specifically shown in Table 1.

[0077] Table 1 Structures of heterocarboxylic acid dimers

[0078]

[0079]

[0080]

[0081]

[0082]

[0083]

[0084] Taking the above-mentioned compounds A1, A2, A3, A14, B1, B6, C1, D1, E1, F1 and G1 as examples, their preparation methods and related test results are shown below.

[0085] Example 1

[0086] Preparation of Compound A1

[0087] (1) 10 mmol of 2-methyl-4-chlorobenzene was added to a 100 mL round-bottom flask, followed by 25 mL of ultra-dry dichloromethane and 12 mmol of ethylene glycol. 12 mmol of EDCI and 12 mmol of DMAP were then added. The reaction flask was then placed on a magnetic stirrer and sealed with a drying tube. After reacting at room temperature for 4 h, the reaction solution was tested by thin layer chromatography (TLC) [V (petroleum ether): V (ethyl acetate) = 3:1]. The progress of the reactants was determined based on the results of the silica gel plate spotting. After the reaction of the raw materials was complete, the reaction was stopped. The reaction solution was poured into a clean beaker and the pH value was adjusted to a weakly alkaline state. The solution was transferred to a separatory funnel and 100 mL of ethyl acetate was added for extraction. The extraction was repeated twice. The ethyl acetate phase was retained and the solution was poured into a 250 mL conical flask. Sufficient anhydrous sodium sulfate and anhydrous sodium chloride were added and shaken well. The solution was allowed to stand for 2 h for drying. The solution was filtered to remove the desiccant, and the solution was concentrated by rotary evaporation and then separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 3:1] to obtain the intermediate 2-methyl-4-chloroethylene glycol monoester compound.

[0088] (2) Add 6mmol of dicamba and 6mmol of 2-methyl-4-chloroethylene glycol monoester compound into a 100mL round-bottom flask, add 25mL of ultra-dry dichloromethane, continue to add 6mmol of EDCI and 6mmol of DMAP, then place the reaction bottle on a magnetic stirrer and seal it with a drying tube. After reacting at room temperature for 4 hours, the reaction solution was detected by thin layer chromatography (TLC) [V (petroleum ether): V (ethyl acetate) = 3:1]. The progress of the reactants was judged according to the spotting situation of the silica gel plate. After the raw materials reacted completely, the reaction was stopped. The reaction solution was poured into a clean beaker and the pH value was adjusted to weak alkalinity. It was transferred to a separatory funnel and 100mL of ethyl acetate was added for extraction. The extraction was repeated 3 times. The ethyl acetate phase was retained, and the solution was poured into a 250mL conical flask, and sufficient anhydrous sodium sulfate and anhydrous sodium chloride were added and shaken well, and then allowed to stand for 2 hours for drying. The solution was filtered to remove the desiccant, and the solution was concentrated by rotary evaporation and then separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 3:1] to obtain the target compound A1.

[0089] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=7.39(d,J=8.7Hz,1H),7.16-7.10(m,2H),7.03(dd,J=8.6,2.7Hz,1H),6.62(d,J= 8.6Hz,1H),4.66(s,2H),4.64-4.60(m,2H),4.54-4.50(m,2H),3.90(s,3H),2.25(s,3H).

[0090] Example 2

[0091] Preparation of Compound A2

[0092] (1) 10 mmol of 2-methyl-4-chloropropane was added to a 100 mL round-bottom flask, followed by 20 mL of ultra-dry dichloromethane and 2 drops of DMF. 12 mmol of oxalyl chloride was slowly added dropwise under ice bath. The reaction was carried out at room temperature for 4 h until the starting material point disappeared. No post-treatment was required to obtain 2-methyl-4-chloropropane chloride for standby use.

[0093] 10 mmol of 2-methyl-4-chloroyl chloride was slowly dripped into a 100 mL round-bottom flask containing 12 mmol of ethanedithiol, 12 mmol of triethylamine and 20 mL of ultra-dry dichloromethane under ice bath conditions. After the addition, the mixture was returned to room temperature and reacted until the raw material point disappeared. The reaction solution was washed with saturated NaHCO 3 The solution was adjusted to neutral and then transferred to a separatory funnel and 100 mL of ethyl acetate was added for extraction. After three extractions, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated by rotary evaporator. Silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 3: 1] was used for separation and purification to obtain the intermediate 2-methyl-4-chloroethanedithiol monothioester compound.

[0094] (2) The subsequent preparation process is similar to step (2) of Example 1, except that the 2-methyl-4-chloroethylene glycol monoester compound is replaced by a 2-methyl-4-chloroethylene dithiol monothioester compound to obtain the target compound A2.

[0095] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=7.48(d,J=8.6Hz,1H),7.16-7.10(m,2H),7.03(dd,J=8.6,2.7Hz,1H),6.71(d,J=8 .6Hz,1H),4.95(s,2H),3.66-3.62(m,2H),3.56-3.52(m,2H),,3.90(s,3H),2.25(s,3H).

[0096] Example 3

[0097] Preparation of Compound A3

[0098] (1) Preparation of intermediate 2-methyl-4-chloroethylenediamine monoamide compound The preparation method is similar to step (1) of Example 1, except that ethylene glycol is replaced by ethylenediamine to obtain intermediate 2-methyl-4-chloroethylenediamine monoamide compound.

[0099] (2) The subsequent preparation process is similar to step (2) of Example 1, except that the 2-methyl-4-chloroethylene glycol monoester compound is replaced by the 2-methyl-4-chloroethylenediamine monoamide compound to obtain the target compound A3.

[0100] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=7.45(d,J=8.6Hz,1H),7.16-7.10(m,2H),7.03(dd,J=8.6,2.7Hz,1H),6.69(d,J= 8.6Hz,1H),4.45(s,2H),3.70-3.64(m,2H),3.57-3.51(m,2H),3.84(s,3H),2.25(s,3H).

[0101] Example 4

[0102] Preparation of compound A14

[0103] (1) Preparation of intermediate 2-methyl-4-chlorohydroquinone monoester compound The preparation method is similar to step (1) of Example 1, except that ethylene glycol is replaced by hydroquinone to obtain intermediate 2-methyl-4-chlorohydroquinone monoester compound.

[0104] (2) The subsequent preparation process is similar to step (2) of Example 1, except that the 2-methyl-4-chloroethylene glycol monoester compound is replaced by the 2-methyl-4-chlorohydroquinone monoester compound to obtain the target compound A14.

[0105] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=7.39(d,J=8.7Hz,1H),7.16-7.10(m,2H),7.03(dd,J=8.6,2.7Hz,1H),6.62(d,J= 8.6Hz,1H),4.66(s,2H),4.64-4.60(m,2H),4.54-4.50(m,2H),3.90(s,3H),2.25(s,3H).

[0106] Example 5

[0107] Preparation of compound B1

[0108] (1) Preparation of intermediate dicamba ethylene glycol monoester compound The same method as in step (1) of Example 1 is used, except that 2-methyl-4-chloro-4-nitropropene is replaced by dicamba to obtain an intermediate dicamba ethylene glycol monoester compound.

[0109] (2) The subsequent preparation process is similar to step (2) of Example 1, except that the 2-methyl-4-chloroethylene glycol monoester compound is replaced by a dicamba glycol monoester compound, and dicamba is replaced by clofopyralid to obtain the target compound B1.

[0110] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=7.37(d,J=8.7Hz,1H),7.12(d,J=8.6Hz,1H),4.88(s,2H),4.61-4.55(m,2H),4.50-4.45(m,2H),3.90(s,3H).

[0111] Example 6

[0112] Preparation of compound B6

[0113] (1) Preparation of intermediate dicamba hydroquinone monoester compound The preparation method is similar to step (1) of Example 5, except that ethylene glycol is replaced by hydroquinone to obtain an intermediate dicamba hydroquinone monoester compound.

[0114] (2) The subsequent preparation process refers to step (2) of Example 5, except that the dicamba ethylene glycol monoester compound is replaced by a dicamba hydroquinone monoester compound to obtain the target compound B6.

[0115] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=7.35(dd,J=8.7,1.4Hz,1H),7.11(d,J=8.7Hz,1H),4.88(d,J=5.3Hz,2H),4.42(dt,J =19.8,6.2Hz,2H),4.32(dt,J=10.6,6.3Hz,2H),3.90(s,3H),2.11(dp,J=12.5,6.3Hz,2H).

[0116] Example 7

[0117] Preparation of compound C1

[0118] (1) The preparation of the intermediate dicamba ethylene glycol monoester compound refers to step (1) of Example 5.

[0119] (2) 10 mmol of 2,4-dichlorophenoxyacetic acid was added to a 100 mL round-bottom flask, and then 20 mL of ultra-dry dichloromethane and 2 drops of DMF were added. 12 mmol of oxalyl chloride was slowly added dropwise under ice bath. The reaction was carried out at room temperature for 4 h until the raw material point disappeared. No post-treatment was required to obtain 2,4-dichlorophenoxyacetyl chloride, which was set aside.

[0120] Add 6mmol of 2,4-dichlorophenoxyacetyl chloride and 6mmol of ethylene glycol monoester of dicamba into a 100mL round-bottom flask, add 25mL of ultra-dry dichloromethane and 6mmol of triethylamine, then place the reaction bottle on a magnetic stirrer and seal it with a drying tube. After reacting at room temperature for 4h, the reaction solution was tested by thin layer chromatography (TLC) [V (petroleum ether): V (ethyl acetate) = 3:1]. The progress of the reactants was judged according to the situation of the silica gel plate spot plate. After the raw materials reacted completely, the reaction was stopped. Pour the reaction solution into a clean beaker and adjust the pH value to weak alkalinity, transfer it to a separatory funnel, add 100mL of ethyl acetate for extraction, and repeat the extraction 3 times. Retain the ethyl acetate phase, pour the solution into a 250mL conical flask, add sufficient anhydrous sodium sulfate and anhydrous sodium chloride, shake well, and let it stand for 2h to dry. The solution was filtered to remove the desiccant, and the solution was concentrated by rotary evaporation and then separated and purified by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 3:1] to obtain the target compound C1.

[0121] NMR data: 1 H NMR (600 MHz, DMSO-d 6)δppm=7.45(s,1H),7.39(d,J=8.6Hz,1H),7.14(d,J=8.6Hz,1H),7.05(dd,J=8.6,2.7Hz,1 H),6.64(d,J=8.6Hz,1H),4.66(s,2H),4.64-4.60(m,2H),4.54-4.50(m,2H),3.90(s,3H),.

[0122] Example 8

[0123] Preparation of compound D1

[0124] (1) Preparation of intermediate 2-methyl-4-chloroethylene glycol monoester compound The preparation method is similar to step (1) of Example 2, except that ethylenedithiol is replaced by ethylene glycol to obtain intermediate 2-methyl-4-chloroethylene glycol monoester compound.

[0125] (2) The subsequent preparation process refers to step (2) of Example 7, except that 2,4-dichlorophenoxyacetic acid is replaced by flucloracic acid, 2,4-dichlorophenoxyacetyl chloride is replaced by flucloracic acid chloride, and dicamba ethylene glycol monoester compound is replaced by 2-methyl-4-chloroethylene glycol monoester compound to obtain the target compound D1.

[0126] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=7.64(dd,J=8.7,7.7Hz,1H),7.21-7.18(m,2H),7.09(dd,J=2.6,0.9Hz,1H),6.99(ddd,J=8.7,2.7,0.6Hz, 1H), 6.60 (d, J = 8.7Hz, 1H), 4.89 (s, 2H), 4.68-4.61 (m, 4H), 4.59-4.54 (m, 2H), 3.96 (d, J = 0.9Hz, 3H), 2.23 (s, 3H).

[0127] Example 9

[0128] Preparation of compound E1

[0129] (1) Preparation of intermediate fluazifop-butyl ethylene glycol monoester compound The preparation method is similar to step (1) of Example 7, except that dicamba is replaced by fluazifop-butyl ethylene glycol monoester compound to obtain intermediate fluazifop-butyl ethylene glycol monoester compound.

[0130] (2) The subsequent preparation process is similar to step (2) of Example 7, except that the ethylene glycol monoester compound of dicamba is replaced by ethylene glycol monoester compound of fluazifop-codone to obtain the target compound E1.

[0131] NMR data:1 H NMR (600 MHz, DMSO-d 6 )δppm=7.64(dd,J=8.7,7.7Hz,1H),7.46(s,1H),7.21-7.18(m,1H),7.09(dd,J=2.6,0.9Hz,1H),7.05(dd,J=8. 6,2.7Hz,1H),6.64(d,J=8.6Hz,1H),4.89(s,2H),4.68-4.61(m,4H),4.59-4.54(m,2H),3.96(d,J=0.9Hz,3H).

[0132] Example 10

[0133] Preparation of compound F1

[0134] (1) Preparation of intermediate fluroxypyr ethylene glycol monoester compound The same method as in Example 1 was used, except that 2-methyl-4-chloro-1-pyridine was replaced by fluroxypyr ethylene glycol monoamide compound to obtain an intermediate 2-methyl-4-chloro-1-pyridine ethylene glycol monoamide compound.

[0135] (2) The subsequent preparation process is similar to step (2) of Example 1, except that the 2-methyl-4-chloroethylene glycol monoester compound is replaced by a chlorpyrifos ethylene glycol monoester compound, and dicamba is replaced by chlorpyrifos ethylene glycol monoester to obtain the target compound F1.

[0136] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=7.58(dd,J=8.7,7.8Hz,1H),7.39(dd,J=8.7,1.6Hz,1H),7.26(d,J=1.7Hz,1H),6.89(s,2H ), 6.45 (s, 2H), 4.91 (d, J = 5.9Hz, 2H), 4.58-4.51 (m, 2H), 4.47-4.39 (m, 2H), 3.93 (d, J = 0.8Hz, 3H).

[0137] Embodiment 11

[0138] Preparation of compound G1

[0139] (1) Preparation of intermediate dichloroquinoline glycol monoester compound Referring to step (1) of Example 1, the difference is that 2-Methyl-4-chloro-1-nitropropene is replaced by dichloroquinoline glycol monoester to obtain the intermediate dichloroquinoline glycol monoester compound.

[0140] (2) The subsequent preparation process is similar to step (2) of Example 1, except that the 2-methyl-4-chloroethylene glycol monoester compound is replaced by a dichloroquinoline glycol monoester compound to obtain the target compound G1.

[0141] NMR data: 1 H NMR (600 MHz, DMSO-d 6 )δppm=8.57(s,1H),8.36(d,J=8.6Hz,1H),7.78(s,1H),7.58(d,J=8.6Hz,1H),7.36(d,J=8.6H z,1H),6.68(d,J=8.6Hz,1H),4.66(s,2H),4.64-4.60(m,2H),4.54-4.50(m,2H),3.90(s,3H).

[0142] Evaluation of herbicidal activity:

[0143] Common weeds such as Abutilon, Amaranthus retroflexus, Echinochloa crusgalli, and Digitaria were selected for efficacy tests to evaluate the herbicidal activity of heterologous carboxylic acid dimers. Two concentrations were set for each agent, and three replicates were set for each concentration. Each replicate had one pot, and each pot had five weeds. The weed control effect was visually investigated 14 days after application. The results are shown in Tables 2 to 8.

[0144] Table 2 The control effect of series A compounds on weeds

[0145]

[0146]

[0147] Table 3 B series compounds against weeds

[0148]

[0149] Table 4 Control effect of C series compounds on weeds

[0150]

[0151] Table 5: Control effect of D series compounds on weeds

[0152]

[0153] Table 6 E series compounds against weeds

[0154]

[0155] Table 7 F series compounds against weeds

[0156]

[0157] Table 8 Control effect of G series compounds on weeds

[0158]

[0159]

[0160] It can be seen from Tables 2 to 8 that the heterologous carboxylic acid dimers synthesized in the present invention all exhibit good herbicidal activity, and the weed control effect is significantly better than that of the parent compound.

[0161] Corn, rice, wheat, sorghum, soybean and peanut were selected for safety test to evaluate the safety of heterologous carboxylic acid dimer on crops. Two concentrations were set for each agent, and three replicates were set for each concentration. Each replicate had one pot and three crops per pot. No heterologous carboxylic acid dimer was used as blank control. The safety of crops was visually investigated 14 days after application. The results are shown in Tables 9 to 15.

[0162] Visual grading standards:

[0163] Excellent: The inhibition rate of crop growth is less than 10% compared with the blank control;

[0164] Good: The crop growth is 10%<inhibition rate<20% compared with the blank control;

[0165] Middle: Crop growth is 20%<inhibition rate<30% compared with the blank control;

[0166] Poor: The crop growth inhibition rate is >30% compared with the blank control.

[0167] Table 9 Safety of series A compounds at 900 mg / L on crops

[0168]

[0169] Table 10 Safety of B series compounds 900 mg / L on crops

[0170]

[0171]

[0172] Table 11 Safety of C series compounds 900 mg / L on crops

[0173]

[0174] Table 12 Safety of D series compounds at 225 mg / L on crops

[0175]

[0176] Table 13 Safety of E series compounds 225 mg / L on crops

[0177]

[0178]

[0179] Table 14 Safety of F series compounds 225 mg / L on crops

[0180]

[0181] Table 15 Safety of G series compounds 900 mg / L on crops

[0182]

[0183] It can be seen from Tables 9 to 15 that the heterologous carboxylic acid dimers synthesized in the present invention all exhibit good crop safety, and compared with the parent compound, their safety to crops is significantly improved or equivalent.

[0184] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A heterologous carboxylic acid dimer, characterized in that: The structural formula of the heterologous carboxylic acid dimer is shown below: Wherein, R1 is selected from one of the following groups: R2 is selected from one of the following groups: X1 and X2 are independently one of O, S and NH; Y is selected from phenyl, pyridyl, piperidyl, pyrimidinyl, tetrahydropyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, thienyl, tetrahydrothienyl, furanyl, pyrazolyl, oxazolyl, isoxazolyl, quinolyl, isoquinolyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cyclopent ... One of pentenyl, cyclopentadienyl, cyclobutanyl and cyclopropanyl; C2-C12 alkyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl; C2-C12 alkenyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl; one of C2-C12 alkynyl substituted or unsubstituted by at least one of halogen, methyl, ethyl, isopropyl, tert-butyl, trifluoromethyl, nitro, cyano, aryl, alkoxy, alkenyl and alkynyl.

2. A heterologous carboxylic acid dimer according to claim 1, characterized in that: In the structural formula of the heterologous carboxylic acid dimer, R1 is selected from one of the following groups: R2 is selected from one of the following groups: X1 and X2 are independently O or S; Y is selected from one of C2-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl and phenyl.

3. The method for preparing a heterologous carboxylic acid dimer according to claim 1 or 2, characterized in that: Selected from one of method A, method B, and method C; The method A comprises the following steps: The acyl chloride containing R1 and the connecting arm are reacted in the presence of a base and a solvent to obtain an intermediate; the acyl chloride containing R2 and the intermediate are reacted in the presence of a base and a solvent to obtain a heterologous carboxylic acid dimer; The method B comprises the following steps: Carrying out a condensation reaction between a carboxylic acid containing R1 and a connecting arm in the presence of a condensing agent, a base and a solvent to obtain an intermediate; carrying out a condensation reaction between a carboxylic acid containing R2 and an intermediate in the presence of a condensing agent, a base and a solvent to obtain a heterologous carboxylic acid dimer; The method C comprises the following steps: The acyl chloride containing R1 and the connecting arm are reacted in the presence of a base and a solvent to obtain an intermediate; the carboxylic acid containing R2 and the intermediate are subjected to a condensation reaction in the presence of a condensing agent, a base and a solvent to obtain a heterologous carboxylic acid dimer; Alternatively, a carboxylic acid containing R1 and a connecting arm are subjected to a condensation reaction in the presence of a condensing agent, a base and a solvent to obtain an intermediate; an acyl chloride containing R2 and an intermediate are reacted in the presence of a base and a solvent to obtain a heterologous carboxylic acid dimer.

4. The method for preparing a heterologous carboxylic acid dimer according to claim 3, characterized in that: The structure of the carboxylic acid containing R1 is The structure of the carboxylic acid containing R2 is The structure of the connecting arm is 5. The method for preparing a heterologous carboxylic acid dimer according to claim 4, characterized in that: The preparation method of the acyl chloride containing R1 is: reacting a carboxylic acid containing R1 and a chlorine-containing compound in the presence of a catalyst and a solvent to obtain an acyl chloride containing R1; The preparation method of the acyl chloride containing R2 is: reacting a carboxylic acid containing R2 and a chlorine-containing compound in the presence of a catalyst and a solvent to obtain the acyl chloride containing R2.

6. The method for preparing a heterologous carboxylic acid dimer according to claim 5, characterized in that: The chlorine-containing compound is one of thionyl chloride, oxalyl chloride and triphosgene.

7. The method for preparing a heterologous carboxylic acid dimer according to claim 3 or 4, characterized in that: In method A and method C, the molar ratio of the acyl chloride containing R1, the base, and the connecting arm is independently 1:1-5:1-4; the molar ratio of the acyl chloride containing R2, the base, and the intermediate is independently 1:1-5:1-4.

8. The method for preparing a heterologous carboxylic acid dimer according to claim 7, characterized in that: In method B and method C, the molar ratio of the carboxylic acid containing R1, the condensing agent, the base, and the connecting arm is independently 1:1.1-5:1.1-5:1.1-4; the molar ratio of the carboxylic acid containing R2, the condensing agent, the base, and the intermediate is independently 1:1-5:1-5:1-4.

9. The method for preparing a heterologous carboxylic acid dimer according to claim 8, characterized in that: In method A and method C, the reaction temperature is independently 25°C or 66-153°C reflux; the reaction time is independently 2-12h; In method B and method C, the temperature of the condensation reaction is independently 25° C. or 66-153° C. reflux; and the time of the condensation reaction is independently 2-12 hours.

10. Use of a heterologous carboxylic acid dimer according to claim 1 or 2 in controlling weeds.

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