Spirocyclic tetramic acid skeleton compounds, processes for their preparation and uses thereof

Abstract

The application discloses a kind of spirocyclic amino acid skeleton compounds, it is compound shown as formula I with structural general formula, there are 29 kinds of compounds.The application also discloses the preparation method of spirocyclic amino acid skeleton compound.The application also discloses the application of spirocyclic amino acid skeleton compound in as or preparation herbicide, in the application in weed control or preparation in weed control preparation, the control object or weed of the herbicide is selected from the group consisting of barnyard grass, dogtail grass, Chinese alpine paper, crabgrass and other monocotyledonous plants, and purslane, amaranthus retroflexus, goosefoot, solanum nigrum, abutilon theophrasti and other dicotyledonous plants.Spirocyclic amino acid skeleton compound of the application is obtained after molecular modification to microsphaeropsis ochracea ketonic acid, and experimental research shows that the weed control effect is good, especially compound C3, compound C22, compound C23, the growth of crop has no influence basically.Spirocyclic amino acid skeleton compound of the application is suitable for industrial production, and has great application potential.

Description

Spirocyclic tertidine skeleton compounds, their preparation methods and applications Technical Field

[0001] This invention relates to a spirocyclic tertamine skeleton compound, its preparation method and application, belonging to the fields of organic chemistry and pesticides. Background Technology

[0002] In order to address the herbicide resistance and environmental pressure caused by traditional pesticides, the development of new green pesticides is gradually turning its attention to natural products.

[0003] Teratin skeleton compounds are a class of nitrogen-containing heterocyclic compounds containing pyrrolidine-2,4-dione or pyrrololin-2-one structures. Natural products containing teratin skeletons can be mainly isolated from various marine and terrestrial organisms such as sponges, cyanobacteria, bacteria, and fungi. They often have a variety of biological activities, such as antioxidation, antitumor, herbicides, and bactericides. For example, Alternaria alternata ketone acid (chemical name: 3-acetyl-4-hydroxy-5-sec-butylpyrrololin-2-one) has herbicidal activity and has little effect on crop growth, but its herbicidal activity is still not ideal. Therefore, the modification and development of the structure of teratin skeleton compounds is of great significance.

[0004] The applicant of this invention previously modified the structure of tert-amino acid skeleton compounds, as detailed in CN117886737A. After molecular modification of *Cladosporium coliformis* ketoacid, 29 spirocyclic tert-amino acid skeleton compounds (4a-4r, 6a, 6c, 8a-8d, 10a-10d, 12a) were obtained. These compounds showed good control effects against both monocot and dicot weeds. However, there is still significant room for modification of tert-amino acid skeleton compounds, and further modification and research are necessary. Summary of the Invention

[0005] In view of the above-mentioned prior art, the present invention provides a class of spirocyclic tertamine skeleton compounds, their preparation method, and their application as or in the preparation of herbicides.

[0006] This invention is achieved through the following technical solution:

[0007] Spirocyclic tertidine skeleton compounds are compounds with the general structural formula shown in Formula I;

[0008]

[0009] Specifically, the spirocyclic tertidine skeleton compound is one of the following compounds (numbered sequentially in this invention as: compound C1, compound C2, compound C3, compound C4, compound C5, compound C6, compound C7, compound C8, compound C9, compound C10, compound C11, compound C12, compound C13, compound C14, compound C15, compound C16, compound C17, compound C18, compound C19, compound C20, compound C21, compound C22, compound C23, compound C24, compound C25, compound C26, compound C27, compound C28, compound C29), preferably compound C3, compound C22, and compound C23.

[0010]

[0011]

[0012] The preparation method of the spirocyclic tertidine skeleton compound is as follows: First, methyl 4-aminotetrahydropyran-4-carboxylate undergoes an amidation reaction with 2,4-dichlorophenylacetic acid; then, the reaction product of the amidation reaction undergoes a Dickmann condensation reaction, and finally, it undergoes an esterification reaction with an acid (R-COOH) to obtain a spirocyclic tertidine skeleton compound C1-C29; wherein, the acid is selected from any one of the following 29: 2,2-dimethylbutyric acid, 3-chlorobenzoic acid, benzoic acid, 4-trifluoromethylbenzoic acid, n-valeric acid, 3-methoxybenzoic acid, 3-methylbenzoic acid. The following 29 acids are listed below: p-chloromethylbenzoic acid, 3,4-difluorobenzoic acid, p-chlorobenzoic acid, p-methylbenzoic acid, 4-phenoxybenzoic acid, p-methoxybenzoic acid, 3,4-dimethylbenzoic acid, 3,5-dimethoxybenzoic acid, m-fluorobenzoic acid, thiophene-2-carboxylic acid, 4-methylsulfonylbenzoic acid, 2-nitro-4-methylsulfonylbenzoic acid, 2-chloro-4-methylsulfonylbenzoic acid, 1-naphthaleneacetic acid, isoquinolinecarboxylic acid, quinoxaloline-5-carboxylic acid, 4-fluorobenzoic acid, hexanoic acid, methylphthalic acid, bromoacetic acid, 2-fluorobenzoic acid, and isovaleric acid.

[0013]

[0014] Furthermore, the preparation method comprises the following steps:

[0015] (1) Synthesis of compound A

[0016] 10 mmol of methyl 4-aminotetrahydropyran-4-carboxylic acid was dissolved in dichloromethane, and 15 mmol of 4-dimethylaminopyridine and 15 mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride were added. A dichloromethane solution containing 15 mmol of 2,4-dichlorophenylacetic acid was added dropwise at room temperature, and the reaction was carried out for 16 hours at room temperature. Excess salt was removed by filtration, and the dichloromethane phase was washed three times with 5% sodium bicarbonate solution and then three times with pure water until the solution was neutral. The solution was dried on anhydrous sodium sulfate, filtered, and the organic phase was evaporated by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain a white solid, which is compound A.

[0017] (2) Synthesis of compound B

[0018] 10 mmol of compound A was dissolved in methanol, and 40 mL of 0.3 M sodium methoxide solution was added. The mixture was heated to 75 °C and refluxed for 4 hours. After cooling to room temperature, the solvent methanol was removed by rotary evaporation. Pure water was added to the residue and the pH was adjusted to 2-3. The residue was filtered to obtain a white solid, which was compound B.

[0019] (3) Synthesis of spirocyclic tertamine skeleton compounds

[0020] Compound B10 mmol was dissolved in dichloromethane, and 15 mmol of 4-dimethylaminopyridine and 15 mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride were added. A dichloromethane solution containing 15 mmol of R-OH was added dropwise at room temperature, and the reaction was allowed to proceed for 16 hours at room temperature. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution, and then three times with pure water until the solution was neutral. The solution was dried over anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain the crude product. The crude product was purified by column chromatography to obtain a white solid, which was the spirocyclic tertidine skeleton compound. The reaction formula is shown below:

[0021]

[0022] The application of the spirocyclic tertamine skeleton compound as a herbicide, in the control of weeds, in the preparation of herbicides, and in the preparation of formulations for the control of weeds.

[0023] Furthermore, the target weeds or pests controlled by the herbicide are selected from monocotyledonous plants and / or dicotyledonous plants. Even further, the monocotyledonous plants are selected from any one or more of barnyard grass, foxtail grass, goosegrass, and crabgrass; the dicotyledonous plants are selected from any one or more of purslane, amaranth, lambsquarters, black nightshade, and velvetleaf.

[0024] Furthermore, for *Eleusine indica*, compounds C2, C6, C15, C16, C18, C22, and C23 showed better control effects; for *Barnyardgrass*, compounds C3 and C23 showed better control effects; for *Digitaria sanguinalis*, compounds C2, C15, and C22 showed better control effects; and for *Setaria viridis*, compounds C6, C15, C16, C22, and C23 showed better control effects. Overall, for monocotyledonous plants, compounds C22 and C23 showed better effects.

[0025] Furthermore, for Chenopodium album, compounds C2, C3, C5, C11, C13, C14, C20, C23, C25, C27, and C28 showed better control effects; for Solanum nigrum, compounds C2, C3, C20, C23, and C26 showed better control effects; for Abutilon theophrasti, compounds C12, C17, C20, C23, C24, C26, and C27 showed better control effects; and for Amaranthus retroflexus, compounds C3, C12, C20, C22, C26, and C27 showed better control effects. In summary, for dicotyledonous plants, compounds C3 and C23 showed the best effects.

[0026] The spirocyclic teratogenic acid skeleton compounds of this invention are obtained by molecular modification of *Lycopodium clavatum* ketoacid. Experimental studies have shown that they have good control effects on both monocot and dicot weeds, significantly better than *Lycopodium clavatum* ketoacid, especially compounds C3, C22, and C23. The spirocyclic teratogenic acid skeleton compounds of this invention have virtually no impact on crop growth and minimal environmental pollution. Furthermore, the spirocyclic teratogenic acid skeleton compounds of this invention use inexpensive and readily available raw materials, and the synthesis method is simple and efficient, making them suitable for industrial production and possessing great application potential.

[0027] The various terms and phrases used in this invention have their general meanings known to those skilled in the art. Attached Figure Description

[0028] Figure 1: Proton NMR spectrum of compound C3.

[0029] Figure 2: Proton NMR spectrum of compound C22.

[0030] Figure 3: Proton NMR spectrum of compound C23. Detailed Implementation

[0031] The present invention will be further described below with reference to embodiments. However, the scope of the present invention is not limited to the following embodiments. Those skilled in the art will understand that various changes and modifications can be made to the present invention without departing from the spirit and scope thereof.

[0032] Unless otherwise specified, the instruments, reagents, and materials used in the following embodiments are all conventional instruments, reagents, and materials already available in the prior art and can be obtained through legitimate commercial channels. Unless otherwise specified, the experimental methods and detection methods used in the following embodiments are all conventional experimental methods and detection methods already available in the prior art.

[0033] The term used in this invention, "TLC", refers to TLC thin-layer chromatography.

[0034] Example 1: Preparation of spirocyclic tertidine skeleton compounds

[0035] Compounds C1 to C29 were prepared using the following method, with the steps as follows:

[0036] (1) Synthesis of compound A

[0037] In a 100 mL pear-shaped flask, methyl 4-aminotetrahydropyran-4-carboxylic acid (10 mmol) was dissolved in anhydrous dichloromethane (30 mL). 4-Dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol) were added dropwise to a dichloromethane solution (10 mL) at room temperature. The reaction was allowed to proceed for 16 hours at room temperature. The reaction was monitored by TLC until complete. Excess salts were removed by filtration. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL), and then three times with pure water (30 mL) until neutral. The dichloromethane phase was dried over anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain a crude product. The crude product was purified by column chromatography to obtain a white solid, which was compound A.

[0038] Compound A: White solid, melting point 103-105°C; yield 95%. ¹H NMR (600 MHz, cd₃od) δ 7.44 (d, J = 2.0 Hz, ¹H), 7.33 (d, J = 8.6 Hz, ¹H), 7.29-7.27 (m, ¹H), 3.78-3.76 (m, 2H), 3.72 (s, 2H), 3.71–3.67 (m, 2H), 3.67 (s, 3H), 2.13-2.08 (m, 2H), 1.96 (d, J = 13.8 Hz, 2H). HRMS [ESI+] for C 15 H 17Cl2NO4[(M+H)+],m / z Calcd:346.0607; Found:346.0610.

[0039] (2) Synthesis of compound B

[0040] In a 200 mL round-bottom flask, compound A (10 mmol) was dissolved in 20 mL of methanol and stirred for five minutes. Then, 40 mL of 0.3 M sodium methoxide solution (12 mmol) was added (Note: 12 mmol refers to the amount of sodium methoxide). The mixture was slowly heated to reflux at 75 °C and reacted for 4 hours, monitored by TLC until complete. After cooling to room temperature, the methanol solvent was removed by rotary evaporation. 12 mL of pure water was added to the residue, and the pH was adjusted to 2–3 with 1 mol / L hydrochloric acid. The mixture was then filtered to obtain a white solid, which was compound B.

[0041] Compound B: White solid, melting point 113-115℃; yield 98.3%. ¹H NMR (600MHz, cd₃od) δ 7.51 (s, ¹H), 7.34 (d, J = 8.4 Hz, ¹H), 7.27 (d, J = 8.2 Hz, ¹H), 4.00 (d, J = 9.7 Hz, 2H), 3.75 (t, J = 12.8 Hz, 2H), 2.24-2.19 (m, 2H), 1.47 (d, J = 13.6 Hz, 2H). HRMS [ESI+] for C 14 H 13 Cl2NO3[(M+H)+],m / z Calcd:314.0345; Found:314.0348.

[0042] (3) Synthesis of compounds C1 to C29

[0043] In a 100 mL flask, compound B (10 mmol) was dissolved in 30 mL of anhydrous dichloromethane. 4-Dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol) were added dropwise. A solution of acid (R-COOH) (15 mmol) in dichloromethane (10 mL) was added dropwise at room temperature. (The acid used was one of 29 different types: 2,2-dimethylbutyric acid, 3-chlorobenzoic acid, benzoic acid, 4-trifluoromethylbenzoic acid, n-valeric acid, 3-methoxy...) Benzoic acid, 3-methylbenzoic acid, p-chloromethylbenzoic acid, 3,4-difluorobenzoic acid, p-chlorobenzoic acid, p-methylbenzoic acid, 4-phenoxybenzoic acid, p-methoxybenzoic acid, 3,4-dimethylbenzoic acid, 3,5-dimethoxybenzoic acid, m-fluorobenzoic acid, thiophene-2-carboxylic acid, 4-methylsulfonylbenzoic acid, 2-nitro-4-methylsulfonylbenzoic acid, 2-chloro-4-methylsulfonylbenzoic acid, 1-naphthaleneacetic acid, isoquinolinecarboxylic acid, quinoxaloline-5-carboxylic acid, 4-fluorobenzoic acid, hexanoic acid, methylphthalic acid, bromoacetic acid, 2-fluorobenzoic acid, isovaleric acid), reacted at room temperature for 16 hours. The reaction was monitored by TLC until the reaction was complete. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL), and then three times with pure water (30 mL) until the solution was neutral. The dichloromethane phase was dried on anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain a crude product. The crude product was purified by column chromatography to obtain a white solid, namely compounds C1-C29. The reaction formula is shown below.

[0044]

[0045] Compound C1: White solid, melting point 101-105 °C; yield 95.3%. ¹H NMR (600 MHz, dmso) δ 9.32 (s, ¹H), 7.64 (s, ¹H), 7.44 (d, J = 8.2 Hz, ¹H), 7.23 (d, J = 8.9 Hz, ¹H), 3.84 (d, J = 9.5 Hz, 2H), 3.68 (t, J = 12.1 Hz, 2H), 1.91 (s, 2H), 1.48 (q, J = 7.6 Hz, 2H), 1.36 (d, J = 13.1 Hz, 2H), 1.07 (s, 6H), 0.58 (t, J = 7.5 Hz, 3H). HRMS [ESI+] for C 20 H 23 Cl2NO4[(M+H)+],m / z Calcd:412.1077; Found:412.1080.

[0046] Compound C2: white solid, melting point 125-127°C; yield 95.3%. ¹H NMR (600MHz, cdCl₃) δ 8.15 (s, ¹H), 7.99 (s, ¹H), 7.92 (d, J = 7.8 Hz, ¹H), 7.63 (d, J = 8.1 Hz, ¹H), 7.46–7.42 (m, 2H), 7.35 (d, J = 2.1 Hz, 1H), 7.32–7.29 (m, ¹H), 4.07 (dd, J = 11.3, 4.0 Hz, 2H), 3.69 (t, J = 11.3 Hz, 2H), 2.27 (s, 2H), 1.65 (d, J = 13.5 Hz, 2H). HRMS [ESI+] for C 21 H 16 Cl3NO4[(M+H)+],m / zCalcd:452.0218; Found:452.0223.

[0047] Compound C3: white solid, melting point 132-135°C; yield 92.3%. ¹H NMR (600MHz, cdCl₃) δ 8.04 (d, J = 8.4 Hz, 2H), 7.97 (s, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.43 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 2.2 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 4.08 (d, J = 12.5 Hz, 2H), 3.69 (t, J = 12.4 Hz, 2H), 2.29 (s, 2H), 1.65 (d, J = 12.9 Hz, 2H). HRMS [ESI+] for C 21 H 17 Cl2NO4[(M+H)+],m / z Calcd:418.0607; Found:418.0610.

[0048] Compound C4: white solid, melting point 109-113°C; yield 96.7%. ¹H NMR (600MHz, cdCl₃) δ 8.16 (d, J = 8.4 Hz, 2H), 7.76 (d, J = 6.7 Hz, 2H), 7.69 (s, 1H), 7.44 (d, J = 9.5 Hz, 1H), 7.34 (s, 1H), 7.31 (d, J = 8.4 Hz, 1H), 4.09 (d, J = 11.4 Hz, 2H), 3.67 (t, J = 12.3 Hz, 2H), 2.27 (s, 2H), 1.66 (d, J = 13.6 Hz, 2H). HRMS [ESI+] for C 22 H 16Cl2F3NO4[(M+H)+],m / z Calcd:486.0481; Found:486.0476.

[0049] Compound C5: white solid, melting point 136–138 °C; yield 95.8%. ¹H NMR (600 MHz, cdCl₃) δ 7.83 (s, ¹H), 7.41 (s, ¹H), 7.34 (d, J = 8.2 Hz, ¹H), 7.30 (d, J = 8.8 Hz, ¹H), 4.05 (d, J = 11.6 Hz, 2H), 3.64 (t, J = 12.3 Hz, 2H), 2.46 (t, J = 7.3 Hz, 2H), 2.15 (s, 2H), 1.58–1.52 (m, 4H), 1.24 (q, J = 7.5 Hz, 2H), 0.87 (t, J = 7.3 Hz, 3H). HRMS [ESI+] for C 19 H 21 Cl2NO4[(M+H)+],m / z Calcd:398.0920; Found:398.0917.

[0050] Compound C6: white solid, melting point 142-146°C; yield 97.1%. ¹H NMR (600MHz, cdCl₃) δ 7.84 (d, J = 7.0 Hz, 1H), 7.66 (s, 1H), 7.55 (t, J = 7.8 Hz, 1H), 7.42 (d, J = 8.7 Hz, 1H), 7.37 (s, 1H), 7.28 (d, J = 8.2 Hz, 1H), 7.00 (t, J = 9.0 Hz, 2H), 4.07 (d, J = 10.6 Hz, 2H), 3.88 (s, 3H), 3.66 (t, J = 11.9 Hz, 2H), 2.30 (s, 2H), 1.63 (d, J = 13.2 Hz, 2H). HRMS [ESI+] for C 22 H 19 Cl2NO5[(M+H)+],m / z Calcd:448.0713; Found:448.0710.

[0051] Compound C7: white solid, melting point 126-129°C; yield 94.2%. ¹H NMR (600MHz, cdCl₃) δ 7.84 (d, J = 7.5 Hz, 1H), 7.82 (s, 1H), 7.80 (s, 1H), 7.46 (d, J = 8.1 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 7.8 Hz, 1H), 7.34 (s, 1H), 7.29 (d, J = 8.4 Hz, 1H), 4.07 (d, J = 9.7 Hz, 2H), 3.68 (t, J = 12.3 Hz, 2H), 2.41 (s, 3H), 2.29 (s, 2H), 1.65 (d, J = 14.2 Hz, 2H). HRMS [ESI+] for C 22 H 19 Cl2NO4[(M+H)+],m / z Calcd:432.0764; Found:432.0760.

[0052] Compound C8: white solid, melting point 142-145°C; yield 92.1%. ¹H NMR (600MHz, cdCl₃) δ 8.03 (d, J = 8.2 Hz, 2H), 7.98 (s, 1H), 7.51 (d, J = 8.2 Hz, 2H), 7.43 (d, J = 8.5 Hz, 1H), 7.34 (s, 1H), 7.30 (d, J = 9.4 Hz, 1H), 4.62 (s, 2H), 4.07 (d, J = 11.2 Hz, 2H), 3.68 (t, J = 12.1 Hz, 2H), 2.27 (s, 2H), 1.66 (s, 2H). HRMS [ESI+] for C 22 H 18 Cl3NO4[(M+H)+],m / z Calcd:466.0374; Found:466.0370.

[0053] Compound C9: white solid, melting point 146–149°C; yield 92.3%. ¹H NMR (600 MHz, cdCl₃) δ 7.87–7.82 (m, 2H), 7.69 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 2.2 Hz, 1H), 7.32–7.28 (m, 2H), 4.09 (dd, J = 12.3, 4.7 Hz, 2H), 3.67 (t, J = 11.6 Hz, 2H), 2.26 (s, 2H), 1.64 (s, 2H). HRMS [ESI+] for C 21 H 15Cl2F2NO4[(M+H)+],m / z Calcd:454.0419; Found:454.0423.

[0054] Compound C10: white solid, melting point 110-113°C; yield 94.6%. ¹H NMR (600MHz, cdCl₃) δ 7.96 (d, J = 6.7 Hz, 2H), 7.68 (s, 1H), 7.47 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 9.7 Hz, 1H), 7.34 (s, 1H), 7.29 (d, J = 9.0 Hz, 1H), 4.08 (d, J = 11.3 Hz, 2H), 3.66 (t, J = 12.0 Hz, 2H), 2.27 (s, 2H), 1.63 (s, 2H). HRMS [ESI+] for C 21 H 16 Cl3NO4[(M+H)+],m / z Calcd:452.0218; Found:452.0218.

[0055] Compound C11: white solid, melting point 138-140°C; yield 97.1%. ¹H NMR (600MHz, cdCl₃) δ 7.92 (d, J = 6.9 Hz, 2H), 7.70 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.33 (s, 1H), 7.28 (d, J = 8.2 Hz, 3H), 4.07 (d, J = 11.9 Hz, 2H), 3.67 (t, J = 11.8 Hz, 2H), 2.44 (s, 3H), 2.28 (s, 2H), 1.65 (d, J = 13.9 Hz, 2H). HRMS [ESI+] for C 22 H 19 Cl2NO4[(M+H)+],m / z Calcd:432.0764; Found:432.0760.

[0056] Compound C12: white solid, melting point 142-144°C; yield 92.2%. ¹H NMR (600MHz, cdCl₃) δ 7.98 (d, J = 8.4 Hz, 2H), 7.54 (s, 1H), 7.42 (d, J = 8.0 Hz, 3H), 7.35 (s, 1H), 7.29 (d, J = 8.3 Hz, 1H), 7.23 (s, 1H), 7.08 (d, J = 7.9 Hz, 2H), 7.00 (d, J = 8.4 Hz, 2H), 4.07 (d, J = 11.9 Hz, 2H), 3.65 (t, J = 12.3 Hz, 2H), 2.27 (s, 2H), 1.64 (d, J = 13.4 Hz, 2H). HRMS [ESI+] for C27 H 21 Cl2NO5[(M+H)+],m / z Calcd:510.0870; Found:510.0874.

[0057] Compound C13: white solid, melting point 151-154°C; yield 91.8%. ¹H NMR (600MHz, cdCl₃) δ 7.98 (d, J = 9.1 Hz, 2H), 7.48 (s, 1H), 7.41 (d, J = 8.9 Hz, 1H), 7.33 (s, 1H), 7.28 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 8.5 Hz, 2H), 4.08 (d, J = 11.7 Hz, 2H), 3.88 (s, 3H), 3.65 (t, J = 12.0 Hz, 2H), 2.28 (s, 2H), 1.64 (d, J = 12.9 Hz, 2H). HRMS [ESI+] for C 22 H 19 Cl2NO5[(M+H)+],m / z Calcd:448.0713; Found:448.0710.

[0058] Compound C14: white solid, melting point 111-115°C; yield 85.7%. ¹H NMR (600 MHz, cdCl₃) δ 7.77 (s, 2H), 7.57 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.33 (s, 1H), 7.28 (d, J = 7.9 Hz, 1H), 7.23 (d, J = 8.2 Hz, 1H), 4.08 (d, J = 10.6 Hz, 2H), 3.66 (t, J = 12.4 Hz, 2H), 2.34 (s, 3H), 2.31 (s, 3H), 1.72 (s, 2H), 1.65 (d, J = 13.9 Hz, 2H). HRMS [ESI+] for C 23 H 21 Cl2NO4[(M+H)+],m / z Calcd:446.0920; Found:446.0924.

[0059] Compound C15: white solid, melting point 137-140°C; yield 93.5%. ¹H NMR (600MHz, cdCl₃) δ 7.41 (d, J = 8.5 Hz, 1H), 7.36 (s, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.15 (s, 2H), 6.72 (s, 1H), 4.08 (d, J = 11.4 Hz, 2H), 3.82 (s, 6H), 3.65 (t, J = 12.2 Hz, 2H), 2.27 (s, 2H), 1.64 (d, J = 13.2 Hz, 2H). HRMS [ESI+] for C 23 H 21 Cl2NO6[(M+H)+],m / z Calcd:478.0819; Found:478.0822.

[0060] Compound C16: white solid, melting point 156-159°C; yield 91.0%. ¹H NMR (600MHz, cdCl₃) δ 8.19 (s, 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.71 (d, J = 9.4 Hz, 1H), 7.48 (d, J = 7.6 Hz, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.36 (s, 2H), 7.30 (d, J = 8.5 Hz, 1H), 4.07 (d, J = 11.7 Hz, 2H), 3.70 (t, J = 12.8 Hz, 2H), 2.27 (s, 2H), 1.65 (d, J = 12.9 Hz, 2H). HRMS [ESI+] for C 21 H 16 Cl2FNO4[(M+H)+],m / z Calcd:436.0513; Found:436.0516.

[0061] Compound C17: white solid, melting point 138-141°C; yield 97.3%. ¹H NMR (600 MHz, cdCl₃) δ 7.88 (s, ¹H), 7.71 (s, ¹H), 7.50 (s, ¹H), 7.42 (d, J = 8.5 Hz, ¹H), 7.36 (s, ¹H), 7.30 (d, J = 8.2 Hz, ¹H), 7.16 (s, ¹H), 4.08 (d, J = 10.9 Hz, 2H), 3.65 (t, J = 12.3 Hz, 2H), 2.28 (s, 2H), 1.64 (d, J = 13.5 Hz, 2H). HRMS [ESI+] for C 19 H 15 Cl2NO4S[(M+H)+],m / z Calcd:424.0172; Found:424.0176.

[0062] Compound C18: white solid, melting point 146-149°C; yield 88.6%. ¹H NMR (600MHz, cdCl₃) δ 8.23 ​​(d, J = 9.4 Hz, 2H), 8.08 (d, J = 7.9 Hz, 2H), 7.70 (s, 1H), 7.44 (d, J = 7.9 Hz, 1H), 7.34 (s, 1H), 7.32 (d, J = 9.1 Hz, 1H), 4.08 (d, J = 10.4 Hz, 2H), 3.66 (t, J = 12.3 Hz, 2H), 3.10 (s, 3H), 2.26 (s, 2H), 1.66 (d, J = 13.2 Hz, 2H). HRMS [ESI+] for C 22 H 19 Cl2NO6S[(M+H)+],m / z Calcd:496.0383; Found:496.0380.

[0063] Compound C19: white solid, melting point 119-124°C; yield 91.9%. ¹H NMR (600 MHz, dmso) δ 9.53 (s, 1H), 8.60 (s, 1H), 8.39 (d, J = 9.7 Hz, 1H), 8.09 (d, J = 7.9 Hz, 1H), 7.67 (s, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.37 (d, J = 7.9 Hz, 1H), 3.87 (d, J = 10.9 Hz, 2H), 3.71 (t, J = 12.0 Hz, 2H), 3.38 (s, 3H), 2.10 (s, 2H), 1.40 (d, J = 13.9 Hz, 2H). HRMS [ESI+] for C 22 H 18 Cl2N2O8S[(M+H)+],m / zCalcd:541.0234; Found:541.0238.

[0064] Compound C20: white solid, melting point 158–161°C; yield 96.8%. ¹H NMR (600 MHz, dmso) δ 9.51 (s, ¹H), 8.20 (d, J = 8.2 Hz, ¹H), 8.14 (d, J = 1.9 Hz, ¹H), 8.02 (d, J = 8.2 Hz, ¹H), 7.64 (d, J = 2.1 Hz, ¹H), 7.47 (d, J = 8.4 Hz, ¹H), 7.40 (d, J = 8.4 Hz, ¹H), 3.87 (dd, J = 11.0, 5.7 Hz, 2H), 3.72 (t, J = 10.9 Hz, 2H), 3.34 (s, 3H), 2.19–2.12 (m, 2H), 1.42 (d, J = 11.7 Hz, 2H). HRMS [ESI+] for C22 H 18 Cl3NO6S[(M+H)+],m / zCalcd:529.9993; Found:529.9997.

[0065] Compound C21: white solid, melting point 129-131°C; yield 89.8%, 1H NMR(600MHz,dmso)δ9.28(s,1H),7.91(d,J=8.1Hz,1H),7.85(d,J=6.3Hz,1H),7 .59(d,J=8.2Hz,1H),7.50(s,2H),7.41(d,J=11.3Hz,3H),7.26(d,J=9.0Hz,1H) ,7.11(d,J=10.9Hz,1H),4.38(s,1H),4.01(s,1H),3.81(d,J=9.7Hz,2H),3.65( t,J=12.5Hz,2H),1.98(t,J=12.6Hz,2H),1.28(d,J=13.4Hz,2H).HRMS[ESI+]for C 26 H 21 Cl2NO4[(M+H)+],m / z Calcd:482.0920; Found:482.0917.

[0066] Compound C22: white solid, melting point 138-140°C; yield 97.8%, 1H NMR(600MHz,cdcl3)δ8.34(d,J=8.7Hz,1H),8.30(d,J=8.5Hz,1H),8.14(d,J=8 .5Hz,1H),7.92(d,J=8.4Hz,1H),7.83-7.81(m,1H),7.71-7.69(m,1H),7.47(d ,J=8.4Hz,1H),7.35(d,J=2.1Hz,1H),7.28-7.26(m,1H),4.13(d,J=14.4Hz,2H ),3.71(t,J=11.0Hz,2H),2.40(s,2H),1.73(d,J=13.6Hz,2H).HRMS[ESI+]for C 24 H 18 Cl2N2O4[(M+H)+],m / z Calcd:469.0716; Found:469.0714.

[0067] Compound C23: white solid, melting point 141-144°C; yield 86.7%. ¹H NMR (600MHz, cdCl₃) δ 8.99 (s, 2H), 8.90 (d, J = 1.9 Hz, 1H), 8.31–8.28 (m, 1H), 8.22 (d, J = 8.8 Hz, 1H), 7.58 (s, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.34–7.31 (m, 2H), 4.11 (d, J = 7.3 Hz, 2H), 3.68 (t, J = 11.4 Hz, 2H), 2.35 (s, 2H), 1.70 (d, J = 12.8 Hz, 2H). HRMS [ESI+] for C 23 H 17 Cl2N3O4[(M+H)+],m / z Calcd:470.0669; Found:470.0665.

[0068] Compound C24: white solid, melting point 128-132°C; yield 97.1%. ¹H NMR (600 MHz, cdCl₃) δ 8.25 (s, ¹H), 8.07–8.03 (m, 2H), 7.42 (d, J = 8.5 Hz, ¹H), 7.35 (d, J = 2.1 Hz, ¹H), 7.31–7.27 (m, ¹H), 7.16 (t, J = 8.6 Hz, 2H), 4.06 (dd, J = 12.3, 5.1 Hz, 2H), 3.70 (t, J = 12.3 Hz, 2H), 2.26 (s, 2H), 1.64 (d, J = 13.5 Hz, 2H). HRMS [ESI+] for C 21 H 16 Cl2FNO4[(M+H)+],m / z Calcd:436.0513; Found:436.0515.

[0069] Compound C25: white solid, melting point 129-133°C; yield 94.7%. ¹H NMR (600MHz, cdCl₃) δ 7.97 (s, ¹H), 7.41 (d, J = 1.9 Hz, ¹H), 7.34 (d, J = 8.4 Hz, ¹H), 7.30 (d, J = 8.4 Hz, ¹H), 4.04 (d, J = 7.3 Hz, 2H), 3.64 (t, J = 12.2 Hz, 2H), 2.46 (t, J = 7.4 Hz, 2H), 2.15 (s, 2H), 1.60–1.52 (m, 4H), 1.30–1.24 (m, 2H), 1.21–1.15 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H). HRMS [ESI+] for C 20 H 23Cl2NO4[(M+H)+],m / z Calcd:412.1077; Found:412.1075.

[0070] Compound C26: white solid, melting point 150-153°C; yield 92.6%. ¹H NMR (600MHz, cdCl₃) δ 7.89 (s, ¹H), 7.41 (d, J = 2.1 Hz, ¹H), 7.35 (d, J = 8.4 Hz, ¹H), 7.30 (d, J = 8.4 Hz, ¹H), 4.05 (d, J = 7.2 Hz, 2H), 3.64 (t, J = 12.4 Hz, 2H), 2.50 (q, J = 7.6 Hz, 2H), 2.16 (s, 2H), 1.53 (s, ¹H), 1.12 (t, J = 7.6 Hz, 3H). HRMS [ESI+] for C 19 H 17 Cl2NO7[(M+H)+],m / z Calcd:414.0506; Found:414.0510.

[0071] Compound C27: white solid, melting point 149-153°C; yield 83.3%. ¹H NMR (600 MHz, cdCl₃) δ 8.04 (s, ¹H), 7.43 (d, J = 2.1 Hz, ¹H), 7.37 (d, J = 8.4 Hz, ¹H), 7.32 (d, J = 6.2 Hz, ¹H), 4.19 (s, 2H), 4.06 (d, J = 9.2 Hz, 2H), 3.67–3.62 (m, 2H), 2.19 (s, 2H), 1.56 (d, J = 13.5 Hz, 2H). HRMS [ESI+] for C 17 H 14 BrCl2NO5[(M+H)+],m / z Calcd:433.9556; Found:433.9559.

[0072] Compound C28: white solid, melting point 106–109 °C; yield 91.6%. ¹H NMR (600 MHz, cdCl₃) δ 7.94–7.89 (m, ¹H), 7.61 (d, J = 22.9 Hz, 2H), 7.44 (d, J = 8.4 Hz, 1H), 7.37 (s, ¹H), 7.30 (d, J = 8.4 Hz, 1H), 7.22–7.17 (m, ¹H), 4.08 (d, J = 12.3 Hz, 2H), 3.65 (t, J = 12.3 Hz, 2H), 2.30 (s, 2H), 1.63 (d, J = 13.6 Hz, 2H). HRMS [ESI+] for C 21 H 16Cl2FNO4[(M+H)+],m / z Calcd:436.0513; Found:436.0516.

[0073] Compound C29: white solid, yield 92.8%. ¹H NMR (600 MHz, cdCl₃) δ 7.92 (s, ¹H), 7.40 (d, J = 1.9 Hz, ¹H), 7.34 (d, J = 8.4 Hz, ¹H), 7.30 (d, J = 6.3 Hz, ¹H), 4.04 (d, J = 6.9 Hz, 2H), 3.64 (t, J = 12.3 Hz, 2H), 2.34 (d, J = 7.2 Hz, 2H), 2.15 (s, 2H), 2.07–2.00 (m, ¹H), 1.54 (d, J = 11.7 Hz, 2H), 0.88 (d, J = 6.7 Hz, 6H). HRMS [ESI+] for C 19 H 21 Cl2NO4[(M+H)+],m / z Calcd:398.0920; Found:398.0924.

[0074] Example 2: Inhibitory effect of spirocyclic tertamine skeleton compounds on weeds

[0075] (1) Pretreatment of test materials: The test seeds (purslane and barnyard grass) were placed in a germination box, an appropriate amount of distilled water was added, and the seeds were soaked in a constant temperature box at 28℃ for 12 hours; the water was filtered out, and the seeds were placed in a germination box at 30℃ to germinate the seeds until they showed white.

[0076] (2) Preparation of primary screening solution: Accurately weigh 25.00 mg of each of the 29 spirocyclic tertidine skeleton compounds (C1-C29) prepared in Example 1, add a small amount of methanol to dissolve them, transfer to a 25 mL volumetric flask, and make up to 25 mL to prepare a 1000 mg / L stock solution for each test compound. Transfer 1 mL of the stock solution to a 15 mL centrifuge tube, add 9 mL of methanol, and dilute to a primary screening solution with a concentration of 100 mg / L.

[0077] Accurately weigh 25.00 mg each of metolachlor, 2,4-D, and cyclohexane ketone acid into a 10 mL centrifuge tube. Dissolve the solutions in a small amount of methanol, transfer the solutions to a 25 mL volumetric flask, and bring the volume to 25 mL to prepare 1000 mg / L stock solutions of metolachlor, 2,4-D, and cyclohexane ketone acid. Transfer 1 mL each of the metolachlor, 2,4-D, and cyclohexane ketone acid stock solutions into a 15 mL centrifuge tube, add 9 mL of methanol, and dilute to prepare a 100 mg / L initial screening control solution.

[0078] (3) Determination of seed germination inhibition rate: Take a petri dish with a diameter of 8.5 cm, place two filter paper discs with a diameter of 8.3 cm in each petri dish, and place 10 test seeds of the same growth state and size in each petri dish. Number and label the seeds, and repeat each treatment three times. Transfer 3 mL of each initial screening solution and the initial screening control solution to the petri dish, and place them in a drying oven at 35℃ for half an hour to remove methanol. After half an hour, add 10 mL of distilled water to the petri dish, cover the dish, and transfer it to an artificial climate incubator for 72 h. After 72 h, measure the root length and shoot length of the seeds in each dish, and calculate the seed germination inhibition rate.

[0079] Seeds of uniform growth in each petri dish were used to measure root and shoot lengths, accurate to one decimal place. Excel software was used for data processing and calculation. Table 1 shows the germination inhibition rates of various spirocyclic teratoside skeleton compounds, as well as S-metolachlor, 2,4-D, and Alternaria alterniflora ketone acid at a concentration of 100 mg / L, on *Portulaca oleracea* and *Barnyardgrass* seeds.

[0080] Table 1 Seed germination inhibition rate (n=35)

[0081]

[0082]

[0083] Example 3: EC inhibitory effect of compound on weed root growth 50 Determination of value

[0084] Based on the results of the measurements in Example 2, compounds C7 and C20 showed better inhibitory effects on purslane, while compounds C16 and C26 showed better inhibitory effects on barnyard grass.

[0085] Compounds C7, C20, C16, C26, and the positive control (2,4-D and metolachlor) were prepared into six concentrations of 100 mg / L, 50 mg / L, 10 mg / L, 1 mg / L, 0.1 mg / L, and 0.01 mg / L, respectively, and placed in 15 mL centrifuge tubes.

[0086] Take 8.5 cm diameter petri dishes, place two 8.3 cm diameter filter paper discs in each dish, and add 10 test seeds (purslane and barnyard grass) of uniform growth state and size to each dish. Number and label the seeds, and repeat each treatment three times. Transfer 3 mL of each concentration of the six compounds prepared above to the petri dishes, place them in a 35°C drying oven for half an hour to remove methanol. After half an hour, add 10 mL of distilled water to the petri dishes, cover them, and incubate them in an artificial climate incubator for 72 hours. After 72 hours, measure the root length of the seeds in each dish and calculate the EC50 of each compound's inhibitory effect on weed root length. 50 The values ​​and results are shown in Table 2 (95% CI of EC). 50 b (Refers to a confidence limit of 0.05).

[0087] Table 2. EC50 of the compounds inhibiting root growth in weeds 50 value

[0088]

[0089] Example 4: Determination of the effectiveness of potted pest control in greenhouses

[0090] (1) Soil treatment methods

[0091] The test materials included dicotyledonous plants such as *Chenopodium album*, *Solanum nigrum*, *Abutilon theophrasti*, and *Amaranthus retroflexus*, and monocotyledonous plants such as *Eleusine indica*, *Digitaria sanguinalis*, *Barnyardgrass*, and *Setaria viridis*. The soil was air-dried sandy loam with an organic matter content ≤2%, neutral pH, good permeability, and sieved. The soil was quantitatively filled to 4 / 5 of the pots and thoroughly moistened using bottom irrigation. Germinated weed seeds (15 seeds / pot) were evenly sown on the soil surface, and then covered with 0.5–2 cm of soil, depending on seed size. Soil spraying was performed 24 hours after sowing. Each treatment was replicated in triplicate. All experiments were conducted under natural light conditions at 18–28°C. For unfavorable weather conditions, sodium vapor lamps were used for illumination, with a 12h:12h light cycle and a dark period.

[0092] Preparation of the solution: Take 29 spirocyclic tertidine skeleton compounds (C1-C29) prepared in Example 1, dissolve them in 1 mL of acetone, and dilute them with 0.1% Tween-80 aqueous solution to a concentration of 6.67 g / L. Use the solution for spraying treatment. Use deionized water as a blank control and use succinate-methyl solution (6.67 g / L) and Alternaria alternata ketone acid solution (6.67 g / L) as positive controls.

[0093] Soil spraying treatment: The tested weeds were placed in an ASS-4 type automatic pesticide spraying system for spraying treatment, using a TEEJET-9503EVS fan-shaped nozzle, with the spray pressure set at 275.8 kPa and the spray volume at 45 mL / m³. 2 Maintain a distance of 50cm between the nozzle and the plant, and then place it in a greenhouse for cultivation after treatment.

[0094] Determination of fresh weight inhibition rate: After 21 days of cultivation, the fresh weight of the aboveground parts of the tested weeds was weighed using a GA110 type electronic balance with a strength of 0.01%, and the fresh weight inhibition rate was calculated as follows: Fresh weight inhibition rate (%) = (fresh weight of control weeds - fresh weight of treated weeds) ÷ fresh weight of control weeds × 100%. The results of the determination of the soil fresh weight inhibition rate of each compound on 4 monocotyledonous plants and 4 dicotyledonous plants are shown in Tables 3 and 4 (the inhibition rate of the blank control was 0, so it was not listed in the table).

[0095] (2) Stem and leaf treatment methods

[0096] Similar to (1) above, the difference is that the positive control drugs were nicosulfuron solution (6.67 g / L) and Alternaria alterniflora ketone solution (6.67 g / L); after the seeds were covered with soil, when the weeds grew to the 3-leaf-1-heart stage, they were placed in the ASS-4 type automatic control pesticide spraying system for spraying. The fresh weight inhibition rate of stems and leaves was calculated (the calculation formula is the same as above). The results of the determination of the fresh weight inhibition rate of stems and leaves of each compound on 4 monocotyledonous plants and 4 dicotyledonous plants are shown in Tables 5 and 6 (the inhibition rate of the blank control was 0, so it was not listed in the table).

[0097] Table 3. Inhibition rate of fresh weight of the compounds on soil treatment of four monocotyledonous plants.

[0098]

[0099]

[0100] Table 4. Inhibition rate of fresh weight of the compounds on soil treatment of four dicotyledonous plants.

[0101]

[0102]

[0103] Table 5. Inhibition rate of fresh weight of the compounds on the stems and leaves of four monocotyledonous plants.

[0104]

[0105] Table 6. Inhibition rate of fresh weight of compounds on stems and leaves of four dicotyledonous plants

[0106]

[0107]

[0108] As shown in Tables 3 and 5, among monocotyledonous plants, for *Eleusine indica*, compounds C2, C6, C15, C18, and C22 showed the highest soil inhibition rates in the soil treatment (88.4%, 81.6%, 89.6%, 94.7%, and 98.7%, respectively), while compounds C16 and C23 showed the highest fresh weight inhibition rates in the stem and leaf treatment (89.3% and 90.3%, respectively). For *Barnyardgrass*, compound C3 showed the highest soil inhibition rate in the soil treatment (82.3%), while compound C23 showed the highest fresh weight inhibition rate in the stem and leaf treatment (89.9%). For *Digitaria sanguinalis*, compound C2 showed the highest soil inhibition rate (84.2%) in soil treatment, while compounds C15 and C22 showed the highest fresh weight inhibition rates (84.1% and 93.3%, respectively) in foliar treatment. For *Setaria viridis*, compounds C22 and C23 showed the highest soil inhibition rates (88.2% and 98.3%, respectively) in soil treatment, while compounds C6, C15, and C16 showed the highest fresh weight inhibition rates (83.5%, 87.2%, and 82.0%, respectively) in foliar treatment (all data are significantly better than the corresponding data for *Alternaria alternifolia* ketone acid). Overall, compounds C22 and C23 showed better efficacy.

[0109] As shown in Tables 4 and 6, among dicotyledonous plants, for *Chenopodium album*, compounds C5, C23, and C25 showed the highest soil inhibition rates in soil treatments, at 92.1%, 93.7%, and 94.2%, respectively. Compounds C3, C11, C14, and C27 all showed inhibition rates above 80%. In stem and leaf treatments, compounds C2 and C20 showed the highest fresh weight inhibition rates, both reaching 100.0%, while compounds C3, C13, and C28 all showed inhibition rates above 80%. For *Solanum nigrum*, compounds C23 and C26 showed the best soil inhibition rates in soil treatments, at 97.6% and 86.1%, respectively. In stem and leaf treatments, compounds C2, C3, C20, and C26 showed the highest fresh weight inhibition rates, at 89.6%, 94.9%, 96.1%, and 94.2%, respectively. 3.6% and 88.3%; for Abutilon theophrasti, compounds C12, C17, and C26 showed the highest soil inhibition rates in soil treatment, at 93.8%, 85.6%, and 85.7%, respectively; while compounds C20, C23, C24, and C27 showed the highest fresh weight inhibition rates in stem and leaf treatment, at 87.4%, 88.6%, 86.7%, and 83.5%, respectively. For Amaranthus retroflexus, compounds C12 and C22 showed the highest soil inhibition rates in soil treatment, at 87.4% and 82.2%, respectively; while compounds C3, C20, C26, and C27 showed the highest fresh weight inhibition rates in stem and leaf treatment, at 95.8%, 97.4%, 91.4%, and 97.8%, respectively (all the data listed above are significantly better than the corresponding data for Alternaria alternifolia ketone acid). Overall, compounds C3 and C23 showed better effects.

[0110] Example 5: Safety evaluation of the compound on cotton and wheat.

[0111] Mix cotton and wheat seeds with soil and sow evenly in the plowed and leveled field. Cover with a thin film and remove the film after the seeds germinate. When the seeds reach the 2-3 leaf stage (about 90% of the seedlings are before the 2-leaf stage), divide the field into plots, each 1m in size. 2 Different concentrations of compound C23 (compound C23 showed high activity against both monocots and dicots, as determined in Example 4) were sprayed, with a solution volume of 100 mL / m². 2 A water control was also included. The fresh weight of seedlings in each treatment was measured 5 and 12 days after application. The fresh weight inhibition rate of compound C23 on cotton and wheat was calculated using the same formula as in Example 4. The plant damage rate of compound C23 on cotton and wheat was calculated using the following formula:

[0112]

[0113] Drug solution preparation: Take compound C23 prepared in Example 1, dissolve it in 1 mL of acetone, and then dilute it with 0.1% Tween-80 aqueous solution to prepare drug solutions with concentrations of 0.67, 1.67, 3.34 and 6.67 g / L.

[0114] The severity of plant diseases caused by compound C23 was evaluated using the criteria shown in Table 7. The statistical results of the severity of plant diseases caused by compound C23 on wheat and cotton are shown in Tables 8 and 9. The plant damage rate and fresh weight inhibition rate of compound C23 on wheat and cotton are shown in Table 10. In Table 10, different lowercase letters in each column indicate significant differences (P < 0.05), and different uppercase letters in each column indicate extremely significant differences (P < 0.01).

[0115] Table 7 Evaluation Criteria for the Severity of Plant Diseases

[0116]

[0117] Table 8. Statistical results of plant disease severity after 5 and 12 days of treatment with compound C23 on wheat (n=25)

[0118]

[0119] Table 9. Statistical results of plant disease severity after 5 and 12 days of treatment with compound C23 on cotton (n=25)

[0120]

[0121]

[0122] Table 10. Plant damage rate and fresh weight inhibition rate of compound C23 on wheat and cotton (n=25)

[0123]

[0124] As shown in Tables 8-10, compound C23 caused relatively little damage to wheat and cotton. Even at a concentration of 6.67 g / L, the plant damage rates to wheat and cotton after 12 days were only 6.4% and 4.8%, respectively, which were significantly different from the low concentration. Twelve days after application, the damage and fresh weight inhibition rates of compound C23 to wheat and cotton were not significantly different from those after 5 days. Therefore, the spirocyclic tertidine skeleton compounds of this invention, represented by compound C23, are relatively safe for crop growth.

[0125] In summary, the spirocyclic tertamine skeleton compounds of the present invention exhibit varying degrees of weed control efficacy depending on the substituent groups, and the pattern is unpredictable. However, it is still evident that they demonstrate good control efficacy against both monocot and dicot weeds. In particular, when the substituent group R is phenyl (corresponding to compound C3), 1-isoquinoline carboxyl (corresponding to compound C22), or quinoxaline-5-carboxyl (corresponding to compound C23), they exhibit excellent control efficacy against both monocot and dicot weeds, significantly superior to Alternaria alternifolia ketone acid. Although its control effect on monocotyledonous weeds is not as good as that of S. metolachlor, the spirocyclic tert-amino acid skeleton compound of the present invention also has a good control effect on dicotyledonous weeds (S. metolachlor has no control effect on dicotyledonous weeds). Similarly, although its control effect on dicotyledonous weeds is not as good as that of nicosulfuron, the spirocyclic tert-amino acid skeleton compound of the present invention also has a good control effect on monocotyledonous weeds (nicosulfuron has no control effect on monocotyledonous weeds), which is significantly better than that of S. metolachlor and nicosulfuron.

[0126] Example 6: Specific preparation of compounds C3, C22, and C23

[0127] (I) Compound C3 is a preferred compound of this invention, and its specific synthesis method is as follows:

[0128] (1) Synthesis of methyl-4-(2-(2,4-dichlorophenyl)acetamido)tetrahydro-2H-pyranocarboxylic acid (compound A)

[0129] In a 100 mL round-bottom flask, methyl 4-aminotetrahydropyran-4-carboxylic acid (1.592 g, 10 mmol) was dissolved in anhydrous dichloromethane (30 mL). 4-Dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol) were added dropwise. A dichloromethane solution (10 mL) of 2,4-dichlorophenylacetic acid (3.075 g, 15 mmol) was added dropwise at room temperature, and the reaction was allowed to proceed for 16 hours at room temperature. The reaction was monitored by TLC until complete. Excess salts were removed by filtration. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL), and then three times with pure water (30 mL) until the solution was neutral. The dichloromethane phase was dried on anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain a crude product. The crude product was purified by column chromatography to obtain a white solid, which is compound A.

[0130] Compound A: White solid, melting point 103-105°C; yield 95%. ¹H NMR (600 MHz, cd₃od) δ 7.44 (d, J = 2.0 Hz, ¹H), 7.33 (d, J = 8.6 Hz, ¹H), 7.29-7.27 (m, ¹H), 3.78-3.76 (m, 2H), 3.72 (s, 2H), 3.71–3.67 (m, 2H), 3.67 (s, 3H), 2.13-2.08 (m, 2H), 1.96 (d, J = 13.8 Hz, 2H). HRMS [ESI+] for C 15 H 17 Cl2NO4[(M+H)+],m / z Calcd:346.0607; Found:346.0610.

[0131] (2) Synthesis of 3-(2,4-dichlorophenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one (compound B)

[0132] In a 200 mL round-bottom flask, compound A (3.462 g, 10 mmol) was dissolved in 20 mL of methanol and stirred for five minutes. Then, 40 mL of 0.3 M sodium methoxide solution (12 mmol) was added (Note: 12 mmol refers to the amount of sodium methoxide). The mixture was slowly heated to 75 °C and refluxed for 4 hours, monitored by TLC until the reaction was complete. After cooling to room temperature, the methanol solvent was removed by rotary evaporation. 12 mL of pure water was added to the residue, and the pH was adjusted to 2–3 with 1 mol / L hydrochloric acid. The mixture was filtered to obtain a white solid, which was compound B.

[0133] Compound B: White solid, melting point 113-115℃; yield 98.3%. ¹H NMR (600MHz, cd₃od) δ 7.51 (s, ¹H), 7.34 (d, J = 8.4Hz, ¹H), 7.27 (d, J = 8.2Hz, ¹H), 4.00 (d, J = 9.7Hz, 2H), 3.75 (t, J = 12.8Hz, 2H), 2.24-2.19 (m, 2H), 1.47 (d, J = 13.6Hz, 2H). HRMS [ESI+] for C₁₄H₁₃Cl₂NO₃[(M+H)⁺], m / z Calcd: 314.0345; Found: 314.0348.

[0134] (3) Synthesis of 3-(2,4-dichlorophenyl)-2-oxo-8-oxa-1-azaspiro[4,5]dec-3-ene-4-benzoic acid (compound C3)

[0135] In a 100 mL flask, compound B (3.142 g, 10 mmol) was dissolved in 30 mL of anhydrous dichloromethane. 4-Dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol) were added dropwise. Benzoic acid (1.832 g, 15 mmol) in dichloromethane solution (10 mL) was added dropwise at room temperature, and the reaction was allowed to proceed for 16 hours. The reaction was monitored by TLC until complete. The dichloromethane phase was washed three times with 30 mL of 5% sodium bicarbonate solution, and then three times with 30 mL of pure water until the solution was neutral. The dichloromethane phase was dried over anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain the crude product. The crude product was purified by column chromatography to obtain a white solid, compound C3, whose 1H NMR spectrum is shown in Figure 1.

[0136] Compound C3: white solid, melting point 132-135°C; yield 92.3%. ¹H NMR (600MHz, cdCl₃) δ 8.04 (d, J = 8.4 Hz, 2H), 7.97 (s, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.43 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 2.2 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 4.08 (d, J = 12.5 Hz, 2H), 3.69 (t, J = 12.4 Hz, 2H), 2.29 (s, 2H), 1.65 (d, J = 12.9 Hz, 2H). HRMS [ESI+] for C 21 H 17 Cl2NO4[(M+H)+],m / z Calcd:418.0607; Found:418.0610.

[0137] (II) Compound C22 is a preferred compound of the present invention, and its specific synthesis method is as follows:

[0138] (1) Synthesis of methyl-4-(2-(2,4-dichlorophenyl)acetamido)tetrahydro-2H-pyranocarboxylic acid (compound A)

[0139] In a 100 mL round-bottom flask, methyl 4-aminotetrahydropyran-4-carboxylic acid (1.592 g, 10 mmol) was dissolved in anhydrous dichloromethane (30 mL). 4-Dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol) were added dropwise. A dichloromethane solution (10 mL) of 2,4-dichlorophenylacetic acid (3.075 g, 15 mmol) was added dropwise at room temperature, and the reaction was allowed to proceed for 16 hours at room temperature. The reaction was monitored by TLC until complete. Excess salts were removed by filtration. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL), and then three times with pure water (30 mL) until the solution was neutral. The dichloromethane phase was dried on anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain a crude product. The crude product was purified by column chromatography to obtain a white solid, which is compound A.

[0140] Compound A: White solid, melting point 103-105°C; yield 95%. ¹H NMR (600 MHz, cd₃od) δ 7.44 (d, J = 2.0 Hz, ¹H), 7.33 (d, J = 8.6 Hz, ¹H), 7.29-7.27 (m, ¹H), 3.78-3.76 (m, 2H), 3.72 (s, 2H), 3.71–3.67 (m, 2H), 3.67 (s, 3H), 2.13-2.08 (m, 2H), 1.96 (d, J = 13.8 Hz, 2H). HRMS [ESI+] for C 15 H 17 Cl2NO4[(M+H)+],m / z Calcd:346.0607; Found:346.0610.

[0141] (2) Synthesis of 3-(2,4-dichlorophenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one (compound B)

[0142] In a 200 mL round-bottom flask, compound A (3.462 g, 10 mmol) was dissolved in 20 mL of methanol and stirred for five minutes. Then, 40 mL of 0.3 M sodium methoxide solution (12 mmol) was added (Note: 12 mmol refers to the amount of sodium methoxide). The mixture was slowly heated to 75 °C and refluxed for 4 hours, monitored by TLC until the reaction was complete. After cooling to room temperature, the methanol solvent was removed by rotary evaporation. 12 mL of pure water was added to the residue, and the pH was adjusted to 2–3 with 1 mol / L hydrochloric acid. The mixture was filtered to obtain a white solid, which was compound B.

[0143] Compound B: White solid, melting point 113-115℃; yield 98.3%. ¹H NMR (600MHz, cd₃od) δ 7.51 (s, ¹H), 7.34 (d, J = 8.4Hz, ¹H), 7.27 (d, J = 8.2Hz, ¹H), 4.00 (d, J = 9.7Hz, 2H), 3.75 (t, J = 12.8Hz, 2H), 2.24-2.19 (m, 2H), 1.47 (d, J = 13.6Hz, 2H). HRMS [ESI+] for C₁₄H₁₃Cl₂NO₃[(M+H)⁺], m / z Calcd: 314.0345; Found: 314.0348.

[0144] (3) Synthesis of 3-(2,4-dichlorophenyl)-2-oxo-8-oxa-1-azaspiro[4,5]dec-3-ene-4-isoquinoline-1-carboxylic acid (compound C22)

[0145] In a 100 mL flask, compound B (3.142 g, 10 mmol) was dissolved in 30 mL of anhydrous dichloromethane. 4-Dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol) were added dropwise. A 10 mL solution of 1-isoquinoline carboxylic acid (2.598 g, 15 mmol) in dichloromethane was added dropwise at room temperature, and the reaction was allowed to proceed for 16 hours. The reaction was monitored by TLC until complete. The dichloromethane phase was washed three times with 30 mL of 5% sodium bicarbonate solution, and then three times with 30 mL of pure water until the solution was neutral. The dichloromethane phase was dried over anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain the crude product. The crude product was purified by column chromatography to obtain a white solid, compound C22, whose 1H NMR structure is shown in Figure 2.

[0146] Compound C22: white solid, melting point 138-140°C; yield 97.8%, 1H NMR(600MHz,cdcl3)δ8.34(d,J=8.7Hz,1H),8.30(d,J=8.5Hz,1H),8.14(d,J=8 .5Hz,1H),7.92(d,J=8.4Hz,1H),7.83-7.81(m,1H),7.71-7.69(m,1H),7.47(d ,J=8.4Hz,1H),7.35(d,J=2.1Hz,1H),7.28-7.26(m,1H),4.13(d,J=14.4Hz,2H ),3.71(t,J=11.0Hz,2H),2.40(s,2H),1.73(d,J=13.6Hz,2H).HRMS[ESI+]for C 24H 18 Cl2N2O4[(M+H)+],m / z Calcd:469.0716; Found:469.0714.

[0147] (III) Compound C23 is a preferred compound of the present invention, and its specific synthesis method is as follows:

[0148] (1) Synthesis of methyl-4-(2-(2,4-dichlorophenyl)acetamido)tetrahydro-2H-pyranocarboxylic acid (compound A)

[0149] In a 100 mL round-bottom flask, methyl 4-aminotetrahydropyran-4-carboxylic acid (1.592 g, 10 mmol) was dissolved in anhydrous dichloromethane (30 mL). 4-Dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol) were added dropwise. A dichloromethane solution (10 mL) of 2,4-dichlorophenylacetic acid (3.075 g, 15 mmol) was added dropwise at room temperature, and the reaction was allowed to proceed for 16 hours at room temperature. The reaction was monitored by TLC until complete. Excess salts were removed by filtration. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL), and then three times with pure water (30 mL) until the solution was neutral. The dichloromethane phase was dried on anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain a crude product. The crude product was purified by column chromatography to obtain a white solid, which is compound A.

[0150] Compound A: White solid, melting point 103-105°C; yield 95%. ¹H NMR (600 MHz, cd₃od) δ 7.44 (d, J = 2.0 Hz, ¹H), 7.33 (d, J = 8.6 Hz, ¹H), 7.29-7.27 (m, ¹H), 3.78-3.76 (m, 2H), 3.72 (s, 2H), 3.71–3.67 (m, 2H), 3.67 (s, 3H), 2.13-2.08 (m, 2H), 1.96 (d, J = 13.8 Hz, 2H). HRMS [ESI+] for C 15 H 17 Cl2NO4[(M+H)+],m / z Calcd:346.0607; Found:346.0610.

[0151] (2) Synthesis of 3-(2,4-dichlorophenyl)-4-hydroxy-8-oxa-1-azaspiro[4,5]dec-3-en-2-one (compound B)

[0152] In a 200 mL round-bottom flask, compound A (3.462 g, 10 mmol) was dissolved in 20 mL of methanol and stirred for five minutes. Then, 40 mL of 0.3 M sodium methoxide solution (12 mmol) was added (Note: 12 mmol refers to the amount of sodium methoxide). The mixture was slowly heated to 75 °C and refluxed for 4 hours, monitored by TLC until the reaction was complete. After cooling to room temperature, the methanol solvent was removed by rotary evaporation. 12 mL of pure water was added to the residue, and the pH was adjusted to 2–3 with 1 mol / L hydrochloric acid. The mixture was filtered to obtain a white solid, which was compound B.

[0153] Compound B: White solid, melting point 113-115℃; yield 98.3%. ¹H NMR (600MHz, cd₃od) δ 7.51 (s, ¹H), 7.34 (d, J = 8.4Hz, ¹H), 7.27 (d, J = 8.2Hz, ¹H), 4.00 (d, J = 9.7Hz, 2H), 3.75 (t, J = 12.8Hz, 2H), 2.24-2.19 (m, 2H), 1.47 (d, J = 13.6Hz, 2H). HRMS [ESI+] for C₁₄H₁₃Cl₂NO₃[(M+H)⁺], m / z Calcd: 314.0345; Found: 314.0348.

[0154] (3) Synthesis of 3-(2,4-dichlorophenyl)-2-oxo-8-oxa-1-azaspiro[4,5]dec-3-ene-4-quinoxaloline-5-carboxylic acid (C23)

[0155] In a 100 mL round-bottom flask, intermediate product B (3.142 g, 10 mmol) was dissolved in anhydrous dichloromethane (30 mL). 4-Dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol) were added dropwise. A dichloromethane solution of quinoxaloline-5-carboxylic acid (2.612 g, 15 mmol) (10 mL) was added dropwise at room temperature, and the reaction was allowed to proceed for 16 hours. The reaction was monitored by TLC until complete. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL), and then three times with pure water (30 mL) until the solution was neutral. The dichloromethane phase was dried over anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain the crude product. The crude product was purified by column chromatography to obtain a white solid, namely compound C23, whose 1H NMR structure is shown in Figure 3.

[0156] Compound C23: white solid, melting point 141-144°C; yield 86.7%. ¹H NMR (600MHz, cdCl₃) δ 8.99 (s, 2H), 8.90 (d, J = 1.9 Hz, 1H), 8.31–8.28 (m, 1H), 8.22 (d, J = 8.8 Hz, 1H), 7.58 (s, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.34–7.31 (m, 2H), 4.11 (d, J = 7.3 Hz, 2H), 3.68 (t, J = 11.4 Hz, 2H), 2.35 (s, 2H), 1.70 (d, J = 12.8 Hz, 2H). HRMS [ESI+] for C 23 H 17 Cl2N3O4[(M+H)+],m / z Calcd:470.0669; Found:470.0665.

[0157] The above embodiments are provided to those skilled in the art to fully disclose and describe how the claimed implementations can be carried out and used, and are not intended to limit the scope of the disclosure herein. Modifications that will be obvious to those skilled in the art will be within the scope of the appended claims.

Claims

1. A spirocyclic terephthalic acid skeleton compound, characterized in that, The structural formula is as follows:

2. The method for preparing the spirocyclic tertidine skeleton compound according to claim 1, characterized in that, The steps are as follows: (1) Synthesis of compound A - methyl-4-(2-(2,4-dichlorophenyl)acetamido)tetrahydro-2H-pyranocarboxylic acid: In a 100 mL flask, methyl 4-aminotetrahydropyran-4-carboxylic acid was taken and dissolved in 30 mL of anhydrous dichloromethane. The mass of methyl 4-aminotetrahydropyran-4-carboxylic acid was 1.592 g and the molar amount was 10 mmol. 4-dimethylaminopyridine and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride were added. The mass of 4-dimethylaminopyridine was 1.833 g and the molar amount was 15 mmol. 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride The salt, with a mass of 2.876 g and a molar mass of 15 mmol, was added dropwise in 10 mL of a dichloromethane solution containing 2,4-dichlorophenylacetic acid (3.075 g, 15 mmol). The reaction was carried out at room temperature for 16 hours. The reaction was monitored by TLC until the reaction was complete. Excess salt was removed by filtration. The dichloromethane phase was washed three times with 30 mL of 5% sodium bicarbonate solution, and then three times with 30 mL of pure water until the solution was neutral. The dichloromethane phase was dried on anhydrous sodium sulfate, filtered, and the organic phase was evaporated by rotary evaporation to obtain the crude product. The crude product was purified by column chromatography to obtain a white solid, which was compound A. (2) Synthesis of Compound B – 3-(2,4-dichlorophenyl)-4-hydroxy-8-oxa-1-azaspirocyclic [4,5]dec-3-en-2-one: In a 200 mL round-bottom flask, compound A was dissolved in 20 mL of methanol. The mass of compound A was 3.462 g and the molar amount was 10 mmol. The mixture was stirred for five minutes, and then 40 mL of 0.3 M sodium methoxide solution (12 mmol) was added. The mixture was then slowly heated to 75 °C and refluxed for 4 hours. The reaction was carried out using TL... C. Follow the reaction until it is complete; after cooling to room temperature, remove the solvent methanol by rotary evaporation, add 12 mL of pure water to the residue, and adjust its pH to 2-3 with 1 mol / L hydrochloric acid. Filter to obtain a white solid, which is compound B; (3) Synthesis of compound C23-3-(2,4-dichlorophenyl)-2-oxo-8-oxa-1-azaspirocyclic[4,5]dec-3-ene-4-quinoxaloline-5-carboxylic acid. In a 100 mL eggplant-shaped flask, dissolve compound B in 30 mL of anhydrous dichloromethane. Compound B, with a mass of 3.142 g and a molar amount of 10 mmol, was added to a mixture of 4-dimethylaminopyridine and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride. The mass of 4-dimethylaminopyridine was 1.833 g and the molar amount was 15 mmol, and the mass of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride was 2.876 g and the molar amount was 15 mmol. Quinoxaloline-5-carboxylic acid (2.612 g, 15 mmol) was then added dropwise at room temperature. 10 mL of chloromethane solution and 2.612 g of quinoxaloline-5-carboxylic acid (15 mmol molar) were reacted at room temperature for 16 hours. The reaction was monitored by TLC until the reaction was complete. The dichloromethane phase was washed three times with 30 mL of 5% sodium bicarbonate solution and then three times with 30 mL of pure water until the solution was neutral. The dichloromethane phase was dried on anhydrous sodium sulfate, filtered, and the organic phase was rotary evaporated to obtain the crude product. The crude product was purified by column chromatography to obtain a white solid, namely compound C23.

3. The use of the spirocyclic tertamine skeleton compound of claim 1 as a herbicide, or in the control of weeds, or in the preparation of herbicides, or in the preparation of formulations for the control of weeds, characterized in that: The herbicide targets foxtail grass and / or velvetleaf.

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