Spiro-specific amino acid framework compound as well as preparation method and application thereof

Abstract

The invention discloses a spiro-specific amino acid skeleton compound which is a compound with a structural general formula as shown in a formula I, and the total number of the compounds is 29. The invention also discloses a preparation method of the spiro-specific amino acid skeleton compound. The invention also discloses an application of the spirotetramic acid skeleton compound in serving as or preparing a herbicide and an application in controlling weeds or preparing a preparation for controlling weeds, and the controlled object or weeds of the herbicide are selected from barnyard grass, green bristlegrass, eleusine indica, digitaria sanguinalis and other monocotyledonous plants. And dicotyledonous plants such as purslane, amaranthus retroflexus, chenopodium album, solanum nigrum and The spirotetramic acid skeleton compound is obtained by performing molecular modification on alternaria tenuissima ketonic acid, and experimental research shows that the spirotetramic acid skeleton compound has a good control effect on weeds, especially a compound C3, a compound C22 and a compound C23, and basically has no influence on the growth of crops. The spiro-specific amino acid skeleton compound is suitable for industrial production and has huge application potential.

Description

Technical Field

[0001] The invention relates to a spirocyclic tert-amino acid skeleton compound and a preparation method and application thereof, and belongs to the field of organic chemistry and pesticides. Background Art

[0002] In order to cope with weed resistance and environmental pressure caused by traditional pesticides, the development of new green pesticides has gradually turned its attention to natural products.

[0003] Tetramine acid skeleton compounds are a class of nitrogen-containing heterocyclic compounds containing pyrrolidine-2,4-dione or pyrrolidine-2-one structures. Natural products containing tetramine acid skeletons can be mainly isolated from various marine products and terrestrial organisms such as sponges, cyanobacteria, bacteria and fungi. They often have multiple biological activities, such as antioxidant, anti-tumor, herbicidal and bactericidal, such as Alternaria tenuifolia acetyl-4-hydroxy-5-sec-butylpyrrolidine-2-one, which has herbicidal activity and has basically no effect on the growth of crops, but its herbicidal activity is still not ideal. Therefore, it is of great significance to transform and develop the structure of tetramine acid skeleton compounds.

[0004] The applicant of the present invention modified the structure of the tert-amino acid skeleton compound in the early stage, as shown in CN117886737A, and obtained 29 spirocyclic tert-amino acid skeleton compounds (4a-4r, 6a, 6c, 8a-8d, 10a-10d, 12a) after molecular modification of the tenuissima acid, and these compounds have good control effects on monocotyledonous weeds and dicotyledonous weeds. However, there is a huge room for modification of the tert-amino acid skeleton compound, and it is still necessary to modify and study it more. Summary of the invention

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

[0006] The present invention is achieved through the following technical solutions:

[0007] The spirocyclic tertamine skeleton compound is a compound having a general structural formula as shown in Formula I;

[0008]

[0009] Specifically, the spirocyclic tert-amino acid skeleton compound is one of the following compounds (the numbers in the present invention are: 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 special amino acid skeleton compound is as follows: first, 4-aminotetrahydropyran-4-carboxylic acid methyl ester and 2,4-dichlorophenylacetic acid are subjected to an amidation reaction; then, the reaction product of the amidation reaction is subjected to a Dickmann condensation reaction, and finally an esterification reaction is carried out with an acid (R-COOH) to obtain spirocyclic special amino acid skeleton compounds C1 to C29; wherein the acid is selected from any one of the following 29 kinds: 2,2-dimethylbutyric acid, 3-chlorobenzoic acid, benzoic acid, 4-trifluoromethylbenzoic acid, n-pentanoic acid, 3-methoxybenzoic acid, 3-methylbenzoic acid Acid, p-chloromethylbenzoic acid, 3,4-difluorobenzoic acid, p-chlorobenzoic acid, p-toluic 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-naphthylacetic acid, isoquinolinecarboxylic acid, quinoxaline-5-carboxylic acid, 4-fluorobenzoic acid, hexanoic acid, methylphthalic acid, bromoacetic acid, 2-fluorobenzoic acid, isovaleric acid; the structural formulas of these 29 acids are as follows:

[0013]

[0014] Furthermore, the steps of the preparation method are as follows:

[0015] (1) Synthesis of Compound A

[0016] Dissolve 10 mmol of methyl 4-aminotetrahydropyran-4-carboxylate in dichloromethane, add 15 mmol of 4-dimethylaminopyridine and 15 mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, add dropwise a dichloromethane solution containing 15 mmol of 2,4-dichlorophenylacetic acid at room temperature, and react at room temperature for 16 hours; remove excess salt by suction filtration, wash the dichloromethane phase with 5% sodium bicarbonate solution 3 times, and then wash with pure water 3 times until the solution is neutral; dry over anhydrous sodium sulfate, filter, and rotary evaporate the organic phase to obtain a crude product, purify the crude product by column chromatography to obtain a white solid, i.e., obtain compound A;

[0017] (2) Synthesis of Compound B

[0018] Dissolve 10 mmol of compound A in methanol, add 40 mL of 0.3 M sodium methoxide solution, heat the mixture to reflux at 75°C, and react for 4 hours; after cooling to room temperature, remove the solvent methanol by rotary evaporation, add pure water to the residue, adjust the pH to 2-3, and filter to obtain a white solid, which is compound B;

[0019] (3) Synthesis of spirocyclic amino acid skeleton compounds

[0020] Dissolve 10mmol of compound B in dichloromethane, add 15mmol of 4-dimethylaminopyridine and 15mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, add dropwise a dichloromethane solution containing 15mmol of R-OH at room temperature, and react at room temperature for 16 hours; wash the dichloromethane phase with 5% sodium bicarbonate solution 3 times, and then wash with pure water 3 times until the solution is neutral; dry over anhydrous sodium sulfate, filter, and rotary evaporate the organic phase to obtain a crude product, purify the crude product by column chromatography to obtain a white solid, that is, obtain a spirocyclic tertamine skeleton compound. The reaction formula is as follows:

[0021]

[0022] The spirocyclic tert-amino acid skeleton compound is used as a herbicide, in controlling weeds, in preparing a herbicide, and in preparing a preparation for controlling weeds.

[0023] Furthermore, the control target or weeds of the herbicide are selected from monocots and / or dicots. Furthermore, the monocots are selected from any one or more of barnyard grass, foxtail grass, goosegrass, and crabgrass; and the dicots are selected from any one or more of purslane, amaranth, quinoa, nightshade, and ramie.

[0024] Furthermore, for Bermuda grass, compound C2, compound C6, compound C15, compound C16, compound C18, compound C22, and compound C23 have better control effects; for barnyard grass, compound C3 and compound C23 have better control effects; for crabgrass, compound C2, compound C15, and compound C22 have better control effects; for Setaria viridis, compound C6, compound C15, compound C16, compound C22, and compound C23 have better control effects; in general, for monocotyledonous plants, compound C22 and compound C23 have better effects.

[0025] Further, for Chenopodium album, compound C2, compound C3, compound C5, compound C11, compound C13, compound C14, compound C20, compound C23, compound C25, compound C27, and compound C28 have better control effects; for Solanum nigrum, compound C2, compound C3, compound C20, compound C23, and compound C26 have better control effects; for Amur ramie, compound C12, compound C17, compound C20, compound C23, compound C24, compound C26, and compound C27 have better control effects; for Amaranthus retroflexus, compound C3, compound C12, compound C20, compound C22, compound C26, and compound C27 have better control effects. In general, for dicotyledonous plants, compound C3 and compound C23 have better effects.

[0026] The spirocyclic special amino acid skeleton compound of the present invention is obtained by molecularly modifying the tenuissima acid. Experimental studies have shown that it has good control effects on monocotyledonous weeds and dicotyledonous weeds, and is significantly better than the tenuissima acid, especially compound C3, compound C22, and compound C23. The spirocyclic special amino acid skeleton compound of the present invention has basically no effect on the growth of crops and has little environmental pollution. The spirocyclic special amino acid skeleton compound of the present invention has cheap and easily available raw materials, a simple and efficient synthesis method, is suitable for industrial production, and has great application potential.

[0027] Various terms and phrases used herein have the general meanings that are well known to those skilled in the art. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 : Hydrogen spectrum structure diagram of compound C3.

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

[0030] Figure 3 : Proton spectrum structure diagram of compound C23. DETAILED DESCRIPTION

[0031] The present invention will be further described below in conjunction with the embodiments. However, the scope of the present invention is not limited to the following embodiments. It will be appreciated by those skilled in the art that various changes and modifications may be made to the present invention without departing from the spirit and scope of the present invention.

[0032] The instruments, reagents, and materials involved in the following examples, unless otherwise specified, are all conventional instruments, reagents, and materials available in the prior art and can be obtained through regular commercial channels. The experimental methods, detection methods, etc. involved in the following examples, unless otherwise specified, are all conventional experimental methods and detection methods available in the prior art.

[0033] The term "TLC" used in the present invention refers to TLC thin layer chromatography technique.

[0034] Example 1 Preparation of Spirocyclic Acid Skeleton Compounds

[0035] Compounds C1 to C29 were prepared by the following preparation methods, respectively, the steps are as follows:

[0036] (1) Synthesis of Compound A

[0037] In a 100 mL eggplant-shaped bottle, 4-aminotetrahydropyran-4-carboxylic acid methyl ester (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, and a dichloromethane solution (10 mL) of 2,4-dichlorophenylacetic acid (3.075 g, 15 mmol) was added dropwise at room temperature, and the mixture was reacted for 16 hours at room temperature. The raw material was tracked by TLC until the reaction was complete. The excess salt was removed by suction filtration, and the dichloromethane phase was washed 3 times with 5% sodium bicarbonate solution (30 mL), and then washed 3 times with pure water (30 mL) until the solution was neutral. The dichloromethane phase was placed on anhydrous sodium sulfate to dry, filtered, and the organic phase was rotary evaporated to obtain a crude product, which was purified by column chromatography to obtain a white solid, namely compound A.

[0038] Compound A: white solid, melting point 103-105; yield 95%, 1H NMR (600MHz, cd3od) δ7.44 (d, J = 2.0Hz, 1H), 7.33 (d, J = 8.6Hz, 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 = 13.8Hz, 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 eggplant-shaped bottle, compound A (10 mmol) was dissolved in methanol (20 mL), stirred for five minutes, 0.3 M sodium methoxide solution (40 mL, 12 mmol) (Note: 12 mmol refers to the amount of sodium methoxide) was added, the mixture was slowly heated to 75 ° C to reflux, reacted for 4 hours, and followed by TLC until the reaction was complete. After cooling to room temperature, the solvent methanol 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, and filtered to obtain a white solid, which was compound B.

[0041] Compound B: white solid, melting point 113-115°C; yield 98.3%. 1H NMR (600MHz, cd3od) δ7.51 (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 eggplant-shaped bottle, compound B (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, and a dichloromethane solution (10 mL) of acid (R-COOH) (15 mmol) was added dropwise at room temperature (there were 29 kinds of acids, namely: 2,2-dimethylbutyric acid, 3-chlorobenzoic acid, benzoic acid, 4-trifluoromethylbenzoic acid, n-pentanoic acid, 3-methoxy The mixture was stirred for 16 hours at room temperature. The raw material was followed by TLC until the reaction was complete. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL) and then washed three times with pure water (30 mL) until the solution was neutral. The dichloromethane phase was placed on anhydrous sodium sulfate for drying, 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, compound C1-C29. The reaction formula is shown below.

[0044]

[0045] Compound C1: white solid, melting point 101-105; yield 95.3%, 1H NMR (600MHz, dmso) δ9.32 (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; yield 95.3%, 1H NMR (600MHz, cdcl3) δ8.15 (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; yield 92.3%, 1H NMR (600MHz, cdcl3) δ8.04 (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; yield 96.7%, 1H NMR (600MHz, cdcl3) δ8.16 (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; yield 95.8%, 1H NMR (600MHz, cdcl3) δ7.83 (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; 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; yield 94.2%, 1H NMR (600MHz, cdcl3) δ 7.84 (d, J = 7.5Hz, 1H), 7.82 (s, 1H), 7.80 (s, 1H), 7.46 (d, J = 8.1Hz, 1H), 7.42 (d, J = 8.4Hz, 1H), 7.38 (d, J = 7.8Hz, 1H), 7.34 (s, 1H), 7.29 (d, J = 8.4Hz, 1H), 4.07 (d, J = 9.7Hz, 2H), 3.68 (t, J = 12.3Hz, 2H), 2.41 (s, 3H), 2.29 (s, 2H), 1.65 (d, J = 14.2Hz, 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; yield 92.1%, 1H NMR (600MHz, cdcl3) δ8.03 (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; yield 92.3%, 1H NMR (600MHz, cdcl3) δ7.87–7.82 (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; yield 94.6%, 1H NMR (600MHz, cdcl3) δ7.96 (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; yield 97.1%, 1H NMR (600MHz, cdcl3) δ7.92 (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; yield 92.2%, 1H NMR (600MHz, cdcl3) δ7.98 (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; yield 91.8%, 1H NMR (600MHz, cdcl3) δ7.98 (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; yield 85.7%, 1H NMR (600MHz, cdcl3) δ7.77 (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; yield 93.5%, 1H NMR (600MHz, cdcl3) δ7.41 (d, J = 8.5Hz, 1H), 7.36 (s, 1H), 7.29 (d, J = 8.4Hz, 1H), 7.15 (s, 2H), 6.72 (s, 1H), 4.08 (d, J = 11.4Hz, 2H), 3.82 (s, 6H), 3.65 (t, J = 12.2Hz, 2H), 2.27 (s, 2H), 1.64 (d, J = 13.2Hz, 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; yield 91.0%, 1H NMR (600MHz, cdcl3) δ8.19 (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; yield 97.3%, 1H NMR (600MHz, 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; yield 88.6%, 1H NMR (600MHz, cdcl3) δ8.23 (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; 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; yield 96.8%, 1H NMR (600MHz, dmso) δ9.51 (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; 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; yield 86.7%, 1H NMR (600MHz, cdcl3) δ8.99 (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; yield 97.1%, 1H NMR (600MHz, cdcl3) δ8.25 (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; yield 94.7%, 1H NMR (600MHz, cdcl3) δ7.97 (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; yield 92.6%, 1H NMR (600MHz, cdcl3) δ7.89 (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; yield 83.3%, 1H NMR (600MHz, cdcl3) δ8.04 (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; yield 91.6%, 1H NMR (600MHz, cdcl3) δ7.94-7.89 (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 Tetramine Acid Skeleton Compounds on Weeds

[0075] (1) Pretreatment of test materials: Place the test seeds (Purslane, Echinochloa crus-galli) in a germination box, add an appropriate amount of distilled water, and soak in a constant temperature box at 28°C for 12 h. Filter out the clean water, place in a germination box again, and place in a constant temperature box at 30°C to germinate the seeds until they turn white.

[0076] (2) Preparation of the primary screening solution: Accurately weigh 25.00 mg of each of the 29 spirocyclic tetraamine skeleton compounds (C1-C29) prepared in Example 1, add a small amount of methanol to dissolve them, transfer them to a 25 mL volumetric flask, dilute to 25 mL, and prepare 1000 mg / L mother solutions of each test compound. Transfer 1 mL of the mother 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 S-isopropylamine, 2,4-D, and Alternaria acid in a 10 mL centrifuge tube, add a small amount of methanol to dissolve, transfer to a 25 mL volumetric flask, dilute to 25 mL, and prepare 1000 mg / L S-isopropylamine mother solution, 2,4-D mother solution, and Alternaria acid mother solution. Transfer 1 mL each of S-isopropylamine mother solution, 2,4-D mother solution, and Alternaria acid mother solution to a 15 mL centrifuge tube, add 9 mL of methanol, and dilute to a primary screening control solution with a concentration of 100 mg / L.

[0078] (3) Determination of seed germination inhibition rate: Take a culture dish with a diameter of 8.5 cm, put two filter papers with a diameter of 8.3 cm in each culture dish, put 10 test seeds of the same growth state and size in each culture dish, number and mark, and repeat the treatment three times. Take 3 mL of each primary screening solution and primary screening control solution, add them to the culture dish, put them in a 35°C drying oven and dry for half an hour to remove methanol. After half an hour, add 10 mL of distilled water to the culture dish, cover the dish, and move it into an artificial climate incubator for 72 hours. After 72 hours, measure the root length and sprout length of the seeds in each dish, and calculate the seed germination inhibition rate.

[0079] The seeds with the same growth degree in each culture dish were taken to measure the root length and the bud length, and the results were accurate to one decimal place. The data were processed and calculated using Excel software. The germination inhibition rates of each spirocyclic amino acid skeleton compound and S-isopropylamine, 2,4-D, and succinic acid on the seeds of Portulaca oleracea and Echinochloa crus-galli at a concentration of 100 mg / L are shown in Table 1.

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

[0081]

[0082]

[0083] EC of the compound in Example 3 for inhibiting the root growth of weeds 50 Determination of value

[0084] From the measurement results in Example 2, it can be seen that compounds C7 and C20 have better inhibitory effects on Portulaca oleracea, and compounds C16 and C26 have better inhibitory effects on Echinochloa crusgalli.

[0085] Compounds C7, C20, C16, C26 and positive controls (2,4-D, S-isopropylamine) were prepared into 6 concentration solutions 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 a culture dish with a diameter of 8.5 cm, put two filter papers with a diameter of 8.3 cm in each culture dish, put 10 test seeds (Purslane, Echinochloa crusgalli) of the same growth state and size in each culture dish, number and mark them, and repeat the treatment three times. Pipette 3 mL of each concentration of the 6 compounds prepared above, add them to the culture dish, and put 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 culture dish, cover the dish with a lid, and move it to an artificial climate incubator for 72 hours. After 72 hours, measure the root length of the seeds in each dish, and calculate the EC value of each compound for the inhibitory effect on the root length of weeds.50 The results are shown in Table 2 (95% CI**of EC 50 b refers to the 0.05 confidence limit).

[0087] Table 2 EC values ​​of compounds for inhibition of weed root growth 50 value

[0088]

[0089] Example 4 Determination of the control effect of greenhouse potted plants

[0090] (1) Soil treatment methods

[0091] Dicotyledonous plants Chenopodium album, Solanum nigrum, Ramie and Amaranthus retroflexus and monocotyledonous plants Goosegrass, Digitaria sanguinea, Echinochloa crusgalli and Setaria viridis were used as test materials. Air-dried sandy loam with an organic matter content of ≤2%, neutral pH, good permeability and sieved was used. The test soil was quantitatively filled to 4 / 5 of the pot, and the bottom of the pot was infiltrated to make the soil completely wet. The germinated and white weed seeds (15 seeds / pot) were evenly sown on the soil surface, and then covered with 0.5-2cm of soil according to the seed size. Soil spray treatment was carried out 24 hours after sowing. Each treatment was repeated 3 times. All experiments were carried out under natural light conditions of 18-28℃. In addition, sodium vapor lamps were used for lighting in unfavorable weather, with a lighting time of 12h:12h and a dark-light cycle.

[0092] Preparation of drug solution: Take 29 kinds of spirocyclic tetraamine skeleton compounds (C1-C29) prepared in Example 1 respectively, dissolve them in 1 mL of acetone, and dilute them with 0.1% Tween-80 aqueous solution to a drug solution with a concentration of 6.67 g / L for spray treatment, with deionized water as a blank control, and with S-isopropylamine solution (6.67 g / L) and Alternaria tenuifolia acid solution (6.67 g / L) as positive controls.

[0093] Soil spray treatment: The weeds were placed in the ASS-4 automatic pesticide spraying system for spraying. The TEEJET-9503EVS fan nozzle was used. The spray pressure was set to 275.8 kPa and the spray volume was set to 45 mL / m 2 The distance between the nozzle and the plant was kept at 50 cm, and the plants were cultured in a greenhouse after treatment.

[0094] Determination of fresh weight inhibition rate: After 21 days of cultivation, the fresh weight of the aboveground part of the tested weeds was weighed using a GA110 1 / 10,000 electronic balance to calculate the fresh weight inhibition rate: 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 is 0, so it is not listed in the table).

[0095] (2) Stem and leaf processing methods

[0096] Same as above (1), except that: the positive control drugs are mesotrione solution (6.67 g / L) and tricholoma acid solution (6.67 g / L); after the seeds are covered with soil, when the weeds grow to the 3-leaf 1-heart stage, they are placed in the ASS-4 automatic control pesticide spraying system for spraying. Calculate the stem and leaf fresh weight inhibition rate (the calculation formula is the same as above). The results of the determination of the stem and leaf fresh weight inhibition rate 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 is 0, so it is not listed in the table).

[0097] Table 3 Inhibition rate of fresh weight of four monocotyledonous plants treated with soil by compounds

[0098]

[0099]

[0100] Table 4 Inhibition rate of fresh weight of four dicotyledonous plants treated with soil by compounds

[0101]

[0102]

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

[0104]

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

[0106]

[0107]

[0108] From Tables 3 and 5, among monocotyledonous plants, for Eleocharis sutchuenensis, the soil inhibition rates of compounds C2, C6, C15, C18 and C22 were the highest in the soil treatment, which were 88.4%, 81.6%, 89.6%, 94.7% and 98.7%, respectively. In the stem and leaf treatment, the fresh weight inhibition rates of compounds C16 and C23 were the highest, which were 89.3% and 90.3%, respectively. For barnyardgrass, the soil inhibition rate of compound C3 was the highest in the soil treatment, which was 82.3%, and the fresh weight inhibition rate of compound C23 was the highest in the stem and leaf treatment, which was 89.9%. For Digitaria, the soil inhibition rate of compound C2 was the highest in the soil treatment, which was 84.2%. The fresh weight inhibition rates of compound C15 and compound C22 were the highest in the stem and leaf treatment, which were 84.1% and 93.3%, respectively. For Setaria, the soil inhibition rates of compound C22 and compound C23 were the highest in the soil treatment, which were 88.2% and 98.3%, respectively. The fresh weight inhibition rates of compound C6, compound C15 and compound C16 were the highest in the stem and leaf treatment, which were 83.5%, 87.2% and 82.0%, respectively (the data listed above are all significantly better than the corresponding data of Alternaria tenuifolia acid). In general, compound C22 and compound C23 have better effects.

[0109] From Table 4 and Table 6, among dicotyledonous plants, for Chenopodium album, in the soil treatment, the soil inhibition rates of compound C5, compound C23, and compound C25 were the highest, which were 92.1%, 93.7%, and 94.2%, respectively. The inhibition rates of compound C3, compound C11, compound C14, and compound C27 were all above 80%. In the stem and leaf treatment, the fresh weight inhibition rates of compound C2 and compound C20 were the highest and both were 100.0%, and the inhibition rates of compound C3, compound C13, and compound C28 were all above 80%. For Solanum nigrum, in the soil treatment, the soil inhibition rates of compound C23 and compound C26 were the best, which were 97.6% and 86.1%, respectively. In the stem and leaf treatment, the fresh weight inhibition rates of compound C2, compound C3, compound C20, and compound C26 were the highest, which were 89.6%, 94.9%, 96.8%, respectively. 3.6%, 88.3%; for Abutilon, in soil treatment, compound C12, compound C17, compound C26 had the highest soil inhibition rates, which were 93.8%, 85.6%, 85.7%, respectively, and in stem and leaf treatment, compound C20, compound 23, compound C24, compound C27 had the highest fresh weight inhibition rates, which were 87.4%, 88.6%, 86.7%, 83.5%, respectively; for Amaranthus retroflexus, in soil treatment, compound C12 and compound C22 had the highest soil inhibition rates, which were 87.4% and 82.2%, respectively, and in stem and leaf treatment, compound C3, compound C20, compound C26, and compound C27 had the highest fresh weight inhibition rates, which were 95.8%, 97.4%, 91.4%, and 97.8%, respectively (the above data are significantly better than the corresponding data of Alternaria tenuifolia acid). In summary, compound C3 and compound C23 have better effects.

[0110] Example 5 Safety Evaluation of Compounds on Cotton and Wheat

[0111] Mix cotton and wheat seeds with soil and spread them evenly in the tilled and leveled field. Cover with film. Remove the film after the seeds germinate. When they grow to 2-3 leaves (about 90% of them are seedlings before 2 leaves), divide them into small plots, each with 1m 2 , spraying with different concentrations of compound C23 (compound C23 has high activity on both monocotyledonous and dicotyledonous leaves as shown in Example 4), the dosage of the solution is 100mL / m 2 , a clear water control was set up, and the fresh weight of the seedlings of each treatment was counted 5d and 12d after the application of the drug. The fresh weight inhibition rate of compound C23 on cotton and wheat was calculated according to the fresh weight inhibition rate formula (the same as the calculation formula in Example 4). The plant injury rate of compound C23 on cotton and wheat was calculated as follows:

[0112]

[0113] Preparation of drug solution: Compound C23 prepared in Example 1 was dissolved in 1 mL of acetone, and then diluted with 0.1% Tween-80 aqueous solution to obtain drug solutions with concentrations of 0.67, 1.67, 3.34, and 6.67 g / L, respectively.

[0114] The severity of plant diseases caused by compound C23 was evaluated, and the evaluation criteria are 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 injury 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 capital letters in each column indicate extremely significant differences (P < 0.01).

[0115] Table 7 Evaluation criteria for plant disease severity

[0116]

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

[0118]

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

[0120]

[0121]

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

[0123]

[0124] As shown in Tables 8 to 10, the damage of compound C23 to wheat and cotton is relatively small. Even at a concentration of 6.67 g / L, the plant damage rates to wheat and cotton after 12 days are only 6.4% and 4.8%, respectively, which are significantly different from those at low concentrations. 12 days after application, the damage and fresh weight inhibition rate of compound C23 to wheat and cotton are not much different from those at 5 days after application. Therefore, the spirocyclic tert-amino acid skeleton compounds of the present invention represented by compound C23 are safe for the growth of crops.

[0125] In summary, the spirocyclic tetraamine skeleton compound of the present invention has different weed control effects due to different substituent groups, and there is no regular pattern. However, it can still be seen that it has a good control effect on both monocotyledonous weeds and dicotyledonous weeds, especially when the substituent group R is phenyl (corresponding to compound C3), 1-isoquinolinecarboxyl (corresponding to compound C22) and quinoxaline-5-carboxyl (corresponding to compound C23), it has an excellent control effect on both monocotyledonous weeds and dicotyledonous weeds, which is significantly better than the tenuissorbic acid. Although the control effect on monocotyledonous weeds is not as good as that of S-isopropylamine, the spirocyclic tetraamine skeleton compound of the present invention also has a good control effect on dicotyledonous weeds (S-isopropylamine has no control effect on dicotyledonous weeds). Similarly, although the control effect on dicotyledonous weeds is not as good as that of mesotrione, the spirocyclic tetraamine skeleton compound of the present invention also has a good control effect on monocotyledonous weeds (mesotrione has no control effect on monocotyledonous weeds), which is significantly better than S-isopropylamine and mesotrione.

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

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

[0128] (1) Synthesis of methyl-4-(2-(2,4-dichlorophenyl)acetylamino)tetrahydro-2H-pyrancarboxylic acid (Compound A)

[0129] In a 100 mL eggplant-shaped bottle, take 4-aminotetrahydropyran-4-carboxylic acid methyl ester (1.592 g, 10 mmol) and dissolve it in anhydrous dichloromethane (30 mL), add 4-dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol), add 2,4-dichlorophenylacetic acid (3.075 g, 15 mmol) in dichloromethane (10 mL) dropwise at room temperature, and react at room temperature for 16 hours. Use TLC to track the raw material until the reaction is complete. Remove excess salt by suction filtration, and wash the dichloromethane phase with 5% sodium bicarbonate solution (30 mL) 3 times, and then wash it with pure water (30 mL) 3 times until the solution is neutral. The dichloromethane phase was placed on anhydrous sodium sulfate for drying, 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 compound A.

[0130] Compound A: white solid, melting point 103-105; yield 95%, 1H NMR (600MHz, cd3od) δ7.44 (d, J = 2.0Hz, 1H), 7.33 (d, J = 8.6Hz, 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 = 13.8Hz, 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 eggplant-shaped bottle, compound A (3.462 g, 10 mmol) was dissolved in methanol (20 mL), stirred for five minutes, 0.3 M sodium methoxide solution (40 mL, 12 mmol) (Note: 12 mmol refers to the amount of sodium methoxide) was added, the mixture was slowly heated to 75 ° C to reflux, reacted for 4 hours, and followed by TLC until the reaction was complete. After cooling to room temperature, the solvent methanol 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, and filtered to obtain a white solid, which was compound B.

[0133] Compound B: white solid, melting point 113-115°C; yield 98.3%. 1H NMR (600MHz, cd3od) δ7.51 (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 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 eggplant-shaped bottle, compound 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, and a dichloromethane solution (10 mL) of benzoic acid (1.832 g, 15 mmol) was added dropwise at room temperature, and the mixture was reacted at room temperature for 16 hours. The raw material was tracked by TLC until the reaction was complete. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL), and then washed three times with pure water (30 mL) until the solution was neutral. The dichloromethane phase was placed on anhydrous sodium sulfate to dry, 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 compound C3, the hydrogen spectrum structure diagram of which is shown in FIG. Figure 1 shown.

[0136] Compound C3: white solid, melting point 132-135; yield 92.3%, 1H NMR (600MHz, cdcl3) δ8.04 (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)acetylamino)tetrahydro-2H-pyrancarboxylic acid (Compound A)

[0139] In a 100 mL eggplant-shaped bottle, take 4-aminotetrahydropyran-4-carboxylic acid methyl ester (1.592 g, 10 mmol) and dissolve it in anhydrous dichloromethane (30 mL), add 4-dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol), add 2,4-dichlorophenylacetic acid (3.075 g, 15 mmol) in dichloromethane (10 mL) dropwise at room temperature, and react at room temperature for 16 hours. Use TLC to track the raw material until the reaction is complete. Remove excess salt by suction filtration, and wash the dichloromethane phase with 5% sodium bicarbonate solution (30 mL) 3 times, and then wash it with pure water (30 mL) 3 times until the solution is neutral. The dichloromethane phase was placed on anhydrous sodium sulfate for drying, 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 compound A.

[0140] Compound A: white solid, melting point 103-105; yield 95%, 1H NMR (600MHz, cd3od) δ7.44 (d, J = 2.0Hz, 1H), 7.33 (d, J = 8.6Hz, 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 = 13.8Hz, 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 eggplant-shaped bottle, compound A (3.462 g, 10 mmol) was dissolved in methanol (20 mL), stirred for five minutes, 0.3 M sodium methoxide solution (40 mL, 12 mmol) (Note: 12 mmol refers to the amount of sodium methoxide) was added, the mixture was slowly heated to 75 ° C to reflux, reacted for 4 hours, and followed by TLC until the reaction was complete. After cooling to room temperature, the solvent methanol 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, and filtered to obtain a white solid, which was compound B.

[0143] Compound B: white solid, melting point 113-115°C; yield 98.3%. 1H NMR (600MHz, cd3od) δ7.51 (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 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 eggplant-shaped bottle, compound 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, and a dichloromethane solution (10 mL) of 1-isoquinolinecarboxylic acid (2.598 g, 15 mmol) was added dropwise at room temperature, and the mixture was reacted for 16 hours at room temperature. The raw material was tracked by TLC until the reaction was complete. The dichloromethane phase was washed three times with 5% sodium bicarbonate solution (30 mL), and then washed 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 a crude product. The crude product was purified by column chromatography to obtain a white solid, i.e., compound C22, the hydrogen spectrum structure of which is shown in FIG. Figure 2 shown.

[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 C24 H 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)acetylamino)tetrahydro-2H-pyrancarboxylic acid (Compound A)

[0149] In a 100 mL eggplant-shaped bottle, take 4-aminotetrahydropyran-4-carboxylic acid methyl ester (1.592 g, 10 mmol) and dissolve it in anhydrous dichloromethane (30 mL), add 4-dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol), add 2,4-dichlorophenylacetic acid (3.075 g, 15 mmol) in dichloromethane (10 mL) dropwise at room temperature, and react at room temperature for 16 hours. Use TLC to track the raw material until the reaction is complete. Remove excess salt by suction filtration, and wash the dichloromethane phase with 5% sodium bicarbonate solution (30 mL) 3 times, and then wash it with pure water (30 mL) 3 times until the solution is neutral. The dichloromethane phase was placed on anhydrous sodium sulfate for drying, 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 compound A.

[0150] Compound A: white solid, melting point 103-105; yield 95%, 1H NMR (600MHz, cd3od) δ7.44 (d, J = 2.0Hz, 1H), 7.33 (d, J = 8.6Hz, 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 = 13.8Hz, 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 eggplant-shaped bottle, compound A (3.462 g, 10 mmol) was dissolved in methanol (20 mL), stirred for five minutes, 0.3 M sodium methoxide solution (40 mL, 12 mmol) (Note: 12 mmol refers to the amount of sodium methoxide) was added, the mixture was slowly heated to 75 ° C to reflux, reacted for 4 hours, and followed by TLC until the reaction was complete. After cooling to room temperature, the solvent methanol 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, and filtered to obtain a white solid, which was compound B.

[0153] Compound B: white solid, melting point 113-115°C; yield 98.3%. 1H NMR (600MHz, cd3od) δ7.51 (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 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-quinoxaline-5-carboxylic acid (C23)

[0155] In a 100 mL eggplant-shaped bottle, take the intermediate product B (3.142 g, 10 mmol) and dissolve it in anhydrous dichloromethane (30 mL), add 4-dimethylaminopyridine (1.833 g, 15 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.876 g, 15 mmol), add quinoxaline-5-carboxylic acid (2.612 g, 15 mmol) in dichloromethane (10 mL) dropwise at room temperature, and react at room temperature for 16 hours. Use TLC to track the raw material until the reaction is complete. The dichloromethane phase is washed 3 times with 5% sodium bicarbonate solution (30 mL), and then washed 3 times with pure water (30 mL) until the solution is neutral. The dichloromethane phase is placed on anhydrous sodium sulfate to dry, filtered, and the organic phase is rotary evaporated to obtain a crude product. The crude product is purified by column chromatography to obtain a white solid, that is, compound C23, the hydrogen spectrum structure diagram is as shown Figure 3 shown.

[0156] Compound C23: white solid, melting point 141-144; yield 86.7%, 1H NMR (600MHz, cdcl3) δ8.99 (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 examples are provided to those skilled in the art to fully disclose and describe how to make and use the claimed embodiments, and are not intended to limit the scope of the disclosure herein. Modifications that are obvious to those skilled in the art will fall within the scope of the appended claims.

Claims

1. A spirocyclic amino acid skeleton compound, characterized in that: One of the following 29 compounds:

2. The method for preparing the spirocyclic amino acid skeleton compound according to claim 1, characterized in that: First, 4-aminotetrahydropyran-4-carboxylic acid methyl ester is subjected to an amidation reaction with 2,4-dichlorophenylacetic acid; then, the reaction product of the amidation reaction is subjected to a Diekmann condensation reaction, and finally an esterification reaction is carried out with an acid to obtain spirocyclic tetraamino acid skeleton compounds C1 to C29; wherein the acid is selected from any one of the following 29 kinds: 2,2-dimethylbutyric acid, 3-chlorobenzoic acid, benzoic acid, 4-trifluoromethylbenzoic acid, n-pentanoic acid, 3-methoxybenzoic acid, 3-methylbenzoic acid, p-chloromethylbenzoic acid Acid, 3,4-difluorobenzoic acid, p-chlorobenzoic acid, p-toluic 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-naphthylacetic acid, isoquinolinecarboxylic acid, quinoxaline-5-carboxylic acid, 4-fluorobenzoic acid, hexanoic acid, methylphthalic acid, bromoacetic acid, 2-fluorobenzoic acid, isovaleric acid.

3. The method for preparing the spirocyclic amino acid skeleton compound according to claim 2, characterized in that: Here are the steps: (1) Synthesis of Compound A Dissolve 10 mmol of methyl 4-aminotetrahydropyran-4-carboxylate in dichloromethane, add 15 mmol of 4-dimethylaminopyridine and 15 mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, add dropwise a dichloromethane solution containing 15 mmol of 2,4-dichlorophenylacetic acid at room temperature, and react at room temperature for 16 hours; remove excess salt by suction filtration, wash the dichloromethane phase with 5% sodium bicarbonate solution 3 times, and then wash with pure water 3 times until the solution is neutral; dry over anhydrous sodium sulfate, filter, and rotary evaporate the organic phase to obtain a crude product, purify the crude product by column chromatography to obtain a white solid, i.e., obtain compound A; (2) Synthesis of Compound B Dissolve 10 mmol of compound A in methanol, add 40 mL of 0.3 M sodium methoxide solution, heat the mixture to reflux at 75°C, and react for 4 hours; after cooling to room temperature, remove the solvent methanol by rotary evaporation, add pure water to the residue, adjust the pH to 2-3, and filter to obtain a white solid, which is compound B; (3) Synthesis of spirocyclic amino acid skeleton compounds Dissolve 10 mmol of compound B in dichloromethane, add 15 mmol of 4-dimethylaminopyridine and 15 mmol of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, add dropwise a dichloromethane solution containing 15 mmol of R-OH at room temperature, and react at room temperature for 16 hours; wash the dichloromethane phase with 5% sodium bicarbonate solution 3 times, and then wash with pure water 3 times until the solution is neutral; dry over anhydrous sodium sulfate, filter, and rotary evaporate the organic phase to obtain a crude product, and purify the crude product by column chromatography to obtain a white solid, i.e., obtain a spirocyclic tertamine skeleton compound.

4. The method for preparing the spirocyclic amino acid skeleton compound according to claim 2, characterized in that: The reaction formula is as follows:

5. Use of the spirocyclic tertiary amino acid skeleton compound according to claim 1 as a herbicide, or in controlling weeds, or in preparing a herbicide, or in preparing a preparation for controlling weeds.

6. The use according to claim 5, characterized in that: The control target or weeds of the herbicide are selected from monocotyledonous plants and / or dicotyledonous plants.

7. The use according to claim 6, characterized in that: The monocotyledonous plant is selected from any one or more of barnyard grass, foxtail grass, goosegrass, and crabgrass; the dicotyledonous plant is selected from any one or more of purslane, amaranth, quinoa, nightshade, and ramie.

8. The use according to claim 7, characterized in that: For monocots, the spirocyclic tert-amino acid skeleton compound is selected from compound C22 and / or compound C23; for dicots, the spirocyclic tert-amino acid skeleton compound is selected from compound C3 and / or compound C23.

9. The use according to claim 7, characterized in that: For Glechoma longituba, the spirocyclic tert-amino acid skeleton compound is selected from any one or more of Compound C2, Compound C6, Compound C15, Compound C16, Compound C18, Compound C22, and Compound C23; For barnyard grass, the spirocyclic tert-amino acid skeleton compound is selected from any one or more of compound C3 and compound C23; For crabgrass, the spirocyclic tert-amino acid skeleton compound is selected from any one or more of compound C2, compound C15, and compound C22; For Setaria viridis, the spirocyclic tert-amino acid skeleton compound is selected from any one or more of compound C6, compound C15, compound C16, compound C22, and compound C23.

10. The use according to claim 7, characterized in that: For Chenopodium album, the spirocyclic tert-butylamine skeleton compound is selected from any one or more of compound C2, compound C3, compound C5, compound C11, compound C13, compound C14, compound C20, compound C23, compound C25, compound C27, and compound C28; For Solanum nigrum, the spirocyclic tert-butyl amino acid skeleton compound is selected from any one or more of compound C2, compound C3, compound C20, compound C23, and compound C26; For ramie, the spirocyclic tert-amino acid skeleton compound is selected from any one or more of compound C12, compound C17, compound C20, compound C23, compound C24, compound C26, and compound C27; For Amaranthus retroflexus, the spirocyclic tert-amino acid skeleton compound is selected from any one or more of Compound C3, Compound C12, Compound C20, Compound C22, Compound C26, and Compound C27.

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