Organic phosphine compound, preparation method therefor, and use thereof

Abstract

The present invention relates to the technical field of chemical pesticides, and in particular to an organic phosphine compound, a preparation method therefor, and a use thereof. The structural formula of the organic phosphine compound is as represented by formula (I), wherein R1 and R2 are respectively C1-C6 alkyl and C1-C6 alkoxy, or R1, R2, and P are connected to each other to form a six-membered ring; R3 is hydrogen, methyl, ethyl, propyl, furyl, thienyl, pyridyl, phenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, or 4-methylphenyl; R4, R5, and R6 each are hydrogen, C1-C3 alkyl, or halogen; and X is C or N. The organic phosphine compound can effectively prevent and control the growth of broadleaf weeds and gramineous weeds post-emergently and has relatively good herbicidal activity. The overall herbicidal activity is higher than that of clacyfos, the herbicidal spectrum of the organic phosphine compound is wider, and the inhibitory activity on various weeds is superior to that of glyphosate. The organic phosphine compound has good application value.

Description

Organic phosphine compound, preparation method and application thereof

[0001] Cross-reference to related applications

[0002] This application claims the benefit of Chinese Patent Application No. 202410594848.5, filed May 14, 2024, and Chinese Patent Application No. 202410594849.X, filed May 14, 2024, the contents of which are incorporated herein by reference. TECHNICAL FIELD

[0003] The present application relates to the technical field of chemical pesticides, in particular to an organic phosphine compound, a preparation method and application thereof. BACKGROUND

[0004] Weed killers capable of controlling monocotyledonous and dicotyledonous weeds are the most demanded herbicides in the world every year. However, due to the small number of varieties and serious resistance development, it is extremely important to develop herbicides with new action mechanisms and new structures capable of controlling monocotyledonous and dicotyledonous weeds. Glyphosate with a phosphonate structure is the most widely used weed killer in the world at present, showing the advantages of low toxicity and strong practicability. Due to the very broad activity and structure relationship of phosphonate compounds, there is good research and development potential. Therefore, it will have good application prospects to develop a new type of highly efficient phosphonate herbicide capable of controlling monocotyledonous and dicotyledonous weeds.

[0005] SUMMARY

[0006] The purpose of the present application is to overcome the problems of the prior art, such as the small number of types of weed killers and serious resistance development, and to provide a new type of organic phosphine compound with an action mechanism different from that of the existing weed killers and having an inhibitory effect on monocotyledonous and dicotyledonous weeds, a preparation method and application thereof.

[0007] In order to achieve the above-mentioned purpose, the present application provides, in one aspect, an organic phosphine compound and its stereoisomer, geometric isomer, tautomer, racemate, nitroxide, hydrate, solvate and pharmaceutically acceptable salt, the structure of the organic phosphine compound is shown in formula (I):

[0008] wherein R 1 and R 2 are each C1-C6 alkyl, C1-C6 alkoxy, or R 1 , R 2 and P are mutually connected to form a six-membered ring; R 3 is hydrogen, methyl, ethyl, propyl, furanyl, thienyl, pyridyl, phenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl or 4-methylphenyl; R 4 , R5 and R 6 each is hydrogen, C1-C3alkyl, or halogen; X is C or N; Z is

[0009] The second aspect of the present application provides a method for preparing the above-mentioned organic phosphine compound, which comprises: reacting a compound represented by formula (II) with a compound represented by formula (III),

[0010] wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X and Z are the same as defined in claim 1, and L is hydrogen or halogen.

[0011] The third aspect of the present application provides a pharmaceutical composition containing the above-mentioned organic phosphine compound or its stereoisomer, geometric isomer, tautomer, racemate, nitroxide, hydrate, solvate and pharmaceutically acceptable salt.

[0012] The fourth aspect of the present application provides the use of the above-mentioned organic phosphine compound and its stereoisomer, geometric isomer, tautomer, racemate, nitroxide, hydrate, solvate and pharmaceutically acceptable salt or the above-mentioned pharmaceutical composition in preventing and treating the growth of weeds.

[0013] The organic phosphine compound described in the present application can effectively prevent and treat the growth of broadleaf weeds and gramineous weeds after seedling, has good herbicidal activity, high overall herbicidal activity, and a wide herbicidal spectrum, and has better inhibitory activity on various weeds than glyphosate, and has good application value. DETAILED DESCRIPTION

[0014] The specific embodiments of the present application are described in detail below. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present application, and are not used to limit the present application.

[0015] The endpoints of the ranges and any values disclosed herein are not limited to the precise values stated. The endpoints of the ranges and the values are approximate values and should be understood as including values approximately near to the stated values. For ranges of values, the endpoints of the ranges are combined with the individual points to form new ranges of values that are not specifically disclosed.

[0016] As used herein, and as used by those in the art, the term "compound of the present application" and its grammatical variations, is intended to include the compound of Formula (I) or a stereoisomer, geometric isomer, tautomer, racemic form, nitroso, hydrate, solvate, and pharmaceutically acceptable salt of the compound of Formula (I).

[0017] As used herein, and as used by those in the art, the term "compound of the present application" and its grammatical variations, is intended to include the compound of Formula (I) or a stereoisomer, geometric isomer, tautomer, racemic form, nitroso, hydrate, solvate, and pharmaceutically acceptable salt of the compound of Formula (I).

[0018] As used herein, and as used by those in the art, the term "compound of the present application" and its grammatical variations, is intended to include the compound of Formula (I) or a stereoisomer, geometric isomer, tautomer, racemic form, nitroso, hydrate, solvate, and pharmaceutically acceptable salt of the compound of Formula (I).

[0019] As used herein, and as used by those in the art, the term "compound of the present application" and its grammatical variations, is intended to include the compound of Formula (I) or a stereoisomer, geometric isomer, tautomer, racemic form, nitroso, hydrate, solvate, and pharmaceutically acceptable salt of the compound of Formula (I).

[0020] As used herein, the term "contacting" is to be given its broadest interpretation and can be any means by which at least two reactants can be brought into chemical reaction, for example, by mixing the two reactants under suitable conditions.

[0021] The present application provides an organic phosphine compound and its stereoisomer, geometric isomer, tautomer, racemate, nitroso, hydrate, solvate and pharmaceutically acceptable salt, the structural formula of the organic phosphine compound is shown as Formula (I):

[0022] wherein, R 1 and R 2 each is C1-C6 alkyl, C1-C6 alkoxy, or R 1 , R 2R is interconnected with P to form a six-membered ring; 3 It is hydrogen, methyl, ethyl, propyl, furanyl, thiophene, pyridyl, phenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, or 4-methylphenyl; R 4 R 5 and R 6 Each is hydrogen, a C1-C3 alkyl group, or a halogen; X is C or N; Z is...

[0023] In this invention, the C1-C6 alkyl groups can be selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl, isohexyl and 3,3-dimethylbutyl.

[0024] In this invention, the C1-C3 alkyl groups can be selected from methyl, ethyl, n-propyl and isopropyl.

[0025] In this invention, C 1- The alkoxy group of C6 can be selected from methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, n-pentoxy, isopentoxy, n-hexyloxy, isohexyloxy, and 3,3-dimethylbutoxy.

[0026] In this invention, the halogen is selected from fluorine, chlorine, bromine and iodine.

[0027] In some embodiments, the organophosphorus compounds provided by the present invention have the structural formulas shown in formula (I-1) or (I-2):

[0028] Wherein, each of the two Rs is either methyl or ethyl; R3 is hydrogen, methyl, ethyl, furanyl, thienyl, or pyridyl; R4 is hydrogen or chlorine; Z is...

[0029] In a preferred embodiment, the organophosphorus compound is selected from the following compounds:

[0030] The structure of the organophosphorus compound described in the above embodiments has not been reported. It has a novel structure and can be effectively used for post-emergence control of broadleaf weeds and grass weeds, demonstrating the characteristics of a non-selective herbicide.

[0031] Specifically, compared with the prior art, the organophosphorus compounds described in the above embodiments have the following advantages:

[0032] (1) The present application introduces 2,4-dichloropyridine carboxylic acid and trichloropyridine oxalic acid structural units into the structure of alpha-oxo phosphonate respectively, and first designs and synthesizes a new type of organic phosphine compound, the structural formula of which is shown as formula (I-1) or formula (I-2). The structure is novel, and is significantly different from the existing organic phosphine compound containing phenoxyacetic acid structural unit in structure. In addition, the structure is also significantly different from the existing phosphonate herbicide glyphosate, and the action mechanism is also significantly different from that of the existing phosphonate herbicide glyphosate. It is a new type of compound;

[0033] (2) Compared with the existing organic phosphine compound containing phenoxyacetic acid structural unit, the organic phosphine compound as shown in formula (I-1) or formula (I-2) of the present application can be effectively used to simultaneously control broadleaf weeds and gramineous weeds, and significantly expand the herbicidal spectrum. The existing alpha-oxo phosphonate containing phenoxyacetic acid structural unit (such as this type of herbicide clacyfos) is mainly used for controlling broadleaf weeds, so the organic phosphine compound of the present application has important research significance and application value for the research and development of new type of high-efficiency non-selective herbicide;

[0034] (3) The preparation method of the organic phosphine compound as shown in formula (I-1) or formula (I-2) is simple, the raw materials are cheap and easy to obtain, the post-reaction treatment is simple, the synthesis efficiency is high, the product prepared has high purity, the production cost is low, and it is beneficial to large-scale production. Further, the method of the present application does not involve complex reaction equipment, and does not require harsh preparation conditions such as high temperature and high pressure, completely meeting the requirements of safe production and green chemistry, and the purification and separation operation of the final product is simple, which is very suitable for industrialized production, and lays a foundation for industrialized application.

[0035] In other embodiments, the organic phosphine compound provided by the present application has a structural formula as shown in formula (I-3):

[0036] wherein, R 3 is methyl, ethyl, propyl, 4-chlorophenyl, phenyl, thienyl, furanyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl or 4-methylphenyl; R 4 , R 5 and R 6 are each hydrogen, methyl or halogen; and X is C or N.

[0037] In preferred cases, the organic phosphine compound is selected from the following compounds:

[0038] The organic phosphine compound described in the above embodiment is novel in structure, has not been reported, and can effectively control the growth of various types of weeds before and after seedling.

[0039] Specifically, compared with the prior art, the organic phosphine compound described in the above embodiment has the following advantages:

[0040] (1) The organic phosphine compound described in the present application has a significant difference in structure from the five types of phosphorus-containing herbicides including phosphite, phosphate, phosphoramidate, phosphonate and phosphinate currently used in the global pesticide market. Among these commonly used phosphorus-containing herbicides, the structure type of phosphine oxide is not included, and there is no report on the application of such a phosphine oxide of formula (I-3) as a herbicide at present, which is a completely new compound.

[0041] (2) Compared with the PDHc inhibitor herbicide clacyfos with a phosphonate structure type, the organic phosphine compound described in the present application not only has a significant difference in structure, but also shows good herbicidal activity on broadleaf weeds and major gramineous weeds before and after seedling, and the herbicidal activity of the organic phosphine compound described in the present application is significantly better than that of the phosphonate herbicide clacyfos at the same dose.

[0042] (3) Compared with the synthesis route of the phosphonate herbicide clacyfos, the synthesis route of the organic phosphine compound of formula (I-3) described above is shorter, only two steps are required to prepare, the starting material is cheap and easy to obtain, the post-treatment is simple, and the target product can be obtained by simple washing, the yield is high (all more than >80%), and the industrialized production is convenient.

[0043] The preparation method of the above organic phosphine compound can comprise: reacting a compound represented by formula (II) with a compound represented by formula (III),

[0044] wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X and Z are the same as defined in claim 1, and L is hydrogen or halogen.

[0045] In some embodiments, the compound represented by formula (II) has a structural formula of formula (II-1), and the compound represented by formula (III) has a structural formula of formula (III-1),

[0046] wherein, two R are each methyl or ethyl; R 3 is hydrogen, methyl, ethyl, furanyl, thienyl or pyridyl; R4 is hydrogen or chlorine; Z is

[0047] The process of the reaction comprises the following steps:

[0048] S1, mixing a compound shown as formula (II), a first acid-binding agent and a first solvent;

[0049] S2, under the condition of stirring, adding a compound shown as formula (III) into the mixture obtained in step S1, and then performing the reaction.

[0050] The organic phosphine compound prepared according to the embodiment has a structural formula shown as formula (I-1),

[0051] In a specific embodiment, in step S1, the compound shown as formula (II-1) and the first acid-binding agent are completely dissolved in the first solvent to obtain a mixture.

[0052] In a preferred embodiment, the first acid-binding agent is pyridine and / or triethylamine.

[0053] In a preferred embodiment, the first solvent is dichloromethane and / or tetrahydrofuran.

[0054] In the present application, in order to further ensure the yield and purity of the compound shown as formula (I-1) prepared, the molar ratio of the amount of the compound shown as formula (II-1), the compound shown as formula (III-1) and the first acid-binding agent in the preparation process is limited to 1:(1-4):(1-5), preferably 1:(2-3):(2-4).

[0055] In a preferred embodiment, in step S2, in order to ensure the sufficient mixing of the reactants and the sufficient progress of the reaction, the compound shown as formula (III-1) can be added into the mixture obtained in step S1 under the condition of low-temperature stirring to perform the reaction, so as to prevent the reactants from reacting too fast when not mixed sufficiently, which leads to the decrease of the purity of the obtained product and the increase of the by-products. Preferably, the temperature during stirring is -10-10°C, and in the present application, the temperature during stirring refers to the temperature of the reaction system during stirring. Specifically, the temperature during stirring can be -10°C, -5°C, 0°C, 5°C or 10°C.

[0056] In a specific embodiment, the specific process of stirring is to first cool the mixture after step S1 to the target temperature, and then perform the stirring at the temperature.

[0057] In a preferred embodiment, in step S2, in order to ensure the solubility of the compound shown as formula (III-1) in the reaction system, the compound shown as formula (III-1) can be first dissolved in a first solvent, and then the obtained solution is added dropwise into the mixture obtained in step S1 for reaction.

[0058] In a preferred embodiment, the reaction conditions include: temperature of 10-50°C, time of 0.5-5h. In the present application, the reaction can be carried out at room temperature, and the reaction condition is mild. Preferably, in order to further ensure the full reaction, stirring can be continued during the reaction, which can be mechanical stirring or magnetic stirring.

[0059] In a specific embodiment, after the reaction, the obtained material is washed with saturated sodium bicarbonate solution, 5% dilute hydrochloric acid and saturated brine in sequence, then dried with anhydrous sodium sulfate, and then suction filtered and desolvated under reduced pressure to obtain the product (the compound shown as formula (I-1)).

[0060] In another embodiment, the compound shown as formula (II) has a structural formula of formula (II-2), and the compound shown as formula (III) has a structural formula of formula (III-1),

[0061] wherein, R 3 is hydrogen, methyl, ethyl, furanyl, thienyl or pyridyl; R 4 is hydrogen or chlorine; and Z is

[0062] The reaction process includes the following steps:

[0063] S3, mixing the compound shown as formula (II-2), a second acid-binding agent and a second solvent;

[0064] S4, under the condition of stirring, adding the compound shown as formula (III-1) into the mixture obtained in step S3, and then carrying out reaction.

[0065] The organic phosphine compound prepared according to the embodiment has a structural formula as shown in formula (I-2),

[0066] In a specific embodiment, in step S3, the compound shown as formula (II-2) and the second acid-binding agent are completely dissolved in the second solvent to obtain a mixture.

[0067] In a preferred embodiment, the second acid-binding agent is pyridine and / or triethylamine.

[0068] In a preferred embodiment, the second solvent is dichloromethane and / or tetrahydrofuran.

[0069] In the present application, the selection of the first and second acid-binding agent does not need to be the same or different, and the selection of the first and second solvent does not need to be the same or different.

[0070] In the present application, in order to further ensure the yield and purity of the compound represented by formula (I-2) prepared, the molar ratio of the compound represented by formula (II-2), the compound represented by formula (III-1) and the first acid-binding agent in the preparation process is limited to 1:(1-4):(1-5), preferably 1:(2-3):(2-4).

[0071] In the preferred embodiment, in step S4, in order to ensure the sufficient mixing of the reactants and the sufficient reaction, the compound represented by formula (III-1) can be added dropwise to the mixture obtained in step S3 under the condition of low-temperature stirring to prevent the reactants from reacting too fast when not mixed sufficiently, which leads to the decrease of the purity of the obtained product and the increase of the by-products. Preferably, the temperature during stirring is -10-10℃, and in the present application, the temperature during stirring refers to the temperature of the reaction system during stirring. Specifically, the temperature during stirring can be -10℃, -5℃, 0℃, 5℃ or 10℃.

[0072] In the specific embodiment, the specific process of stirring is to first cool the mixture after step S3 to the target temperature, and then stir at this temperature.

[0073] In the preferred embodiment, in step S4, in order to ensure the solubility of the compound represented by formula (III-1) in the reaction system, the compound represented by formula (III-1) can be first dissolved in the second solvent, and then the obtained material after dissolution is added dropwise to the mixture obtained in step S3 for reaction.

[0074] In the preferred embodiment, in step S4, the reaction conditions include a temperature of 10-50℃ and a time of 0.5-5h. In the present application, the reaction can be carried out at room temperature, and the reaction conditions are mild. Preferably, in order to further ensure the sufficient reaction, stirring can be continued during the reaction, which can be mechanical stirring or magnetic stirring.

[0075] In the specific embodiment, after the reaction is completed, the obtained material after reaction is washed with saturated sodium bicarbonate solution, 5% dilute hydrochloric acid and saturated brine, then dried with anhydrous sodium sulfate, and then suction filtered and desolvated under reduced pressure to obtain the product (the compound represented by formula (I-2)).

[0076] In some embodiments, the compound of formula (II) has a structural formula of formula (II-3), and the compound of formula (III) has a structural formula of formula (III-2),

[0077] wherein R 3 is methyl, ethyl, propyl, 4-chlorophenyl, phenyl, thienyl, furanyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, or 4-methylphenyl; R 4 , R 5 , and R 6 are each hydrogen, methyl, or halogen; and X is C or N.

[0078] The process of the reaction comprises the following steps:

[0079] S5, mixing the compound of formula (III-2), a third solvent, and a condensing agent to react;

[0080] S6, mixing the compound of formula (II-3), a catalyst, and the material obtained in step S5 to react.

[0081] The organic phosphine compound prepared according to this embodiment has a structural formula of formula (I-3),

[0082] In a specific embodiment, in step S5, to ensure sufficient mixing and contacting of the reactants, the compound of formula (III-2) can be first dissolved in a third solvent, and then the temperature of the obtained mixed solution is lowered to -5-0°C, and then a solution containing the condensing agent is added dropwise to the mixed solution after being cooled, and the reaction is carried out after the reaction system is warmed to the reaction temperature.

[0083] In a specific embodiment, in step S5, to ensure sufficient mixing and contacting of the reactants, the condensing agent can be first dissolved in an organic solvent, and then the obtained solution containing the condensing agent is added dropwise to the mixed solution to carry out the reaction.

[0084] In the present application, in step S5, the reaction conditions can include a temperature of 10-40°C and a time of 5-30 min. Specifically, the reaction temperature can be 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, or 40°C; and the reaction time can be 5 min, 10 min, 15 min, 20 min, 25 min, or 30 min.

[0085] In a preferred embodiment, the solvent is selected from one or two or more of acetonitrile, dichloromethane, and tetrahydrofuran.

[0086] In a preferred embodiment, the condensing agent is selected from one or more of dicyclohexyl carbodiimide (DCC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) and carbonyldiimidazole (CDI).

[0087] In a preferred embodiment, the catalyst is 4-N,N-dimethylpyridine (DMAP) and / or 1-hydroxybenzotriazole (HOBt).

[0088] In the present application, in step S6, the reaction conditions can include a temperature of 20-80℃ and a time of 3-10h. Specifically, the reaction temperature can be 20℃, 25℃, 30℃, 35℃, 40℃, 45℃, 50℃, 55℃, 60℃, 65℃, 70℃, 75℃ or 80℃; and the reaction time can be 3h, 4h, 5h, 6h, 7h, 8h, 9h or 10h.

[0089] In a preferred embodiment, the molar ratio of the compound of formula (II-3), the compound of formula (III-2), the condensing agent and the catalyst is 1:(1-1.2):(1-1.2):(0.05-0.1), more preferably 1:(1.05-1.15):(1.05-1.15):(0.06-0.08).

[0090] In a specific embodiment, in the reaction process of step S5 and step S6, to ensure the full progress of the reaction, stirring can be applied to the system during the reaction to facilitate the full contact and mixing of the reactants.

[0091] The present application also provides a pharmaceutical composition containing the organic phosphine compound provided by the present application or its stereoisomer, geometric isomer, tautomer, racemate, nitroxide, hydrate, solvate and pharmaceutically acceptable salt. Further, the pharmaceutical composition contains an effective amount of the organic phosphine compound. The effective amount refers to the amount of the organic phosphine compound added in the application to achieve the desired effect.

[0092] Further, the pharmaceutical composition of the present application can also optionally contain a pharmaceutically acceptable adjuvant, such as a carrier, excipient. In a specific embodiment, the adjuvant can be at least one of a disintegrant, a glidant, a lubricant, a diluent or a filler, a binder, a colorant.

[0093] The present application also provides the use of the above-mentioned organic phosphine compound and its stereoisomer, geometric isomer, tautomer, racemate, nitroxide, hydrate, solvate and pharmaceutically acceptable salt or the above-mentioned pharmaceutical composition in preventing and treating the growth of weeds.

[0094] In some embodiments, when the organophosphorus compound is a compound represented by formula (I-1) and / or formula (I-2) above, the organophosphorus compound or pharmaceutical composition can be used for post-emergence control of broadleaf weeds and grass weeds.

[0095] In this invention, the broadleaf (dicotyledonous) weeds are selected from at least one of the following: cocklebur, amaranth, cassia seed, mustard greens, velvetleaf, alfalfa, honesty, morning glory, clover, speedwell, purslane, rice bud grass, lambsquarters, sorrel, eclipta prostrata, pokeweed, beggar-ticks, shepherd's purse, chickweed, sedge, lilyturf, fleabane, alligator weed, or perilla.

[0096] In this invention, the grass (monocot) weeds are at least one of the following: foxtail grass, crabgrass, ryegrass, false sorghum, barnyard grass, nitrifying grass, wild oats, Kentucky bluegrass, goosegrass, purslane, bulrush, or foxtail grass.

[0097] In other embodiments, when the organophosphorus compound is a compound represented by formula (I-3) above, the organophosphorus compound or pharmaceutical composition can be used for pre- and post-emergence weed control. This organophosphorus compound or pharmaceutical composition exhibits good activity against various types of weeds both pre- and post-emergence, and demonstrates excellent herbicidal activity by inhibiting the activity of pyruvate dehydrogenase systems in plants.

[0098] In this invention, the weeds can be broadleaf weeds or grass weeds, such as at least one selected from the following: cocklebur, amaranth, cassia seed, mustard greens, velvetleaf, alfalfa, honesty, morning glory, clover, speedwell, purslane, rice leaf grass, lambsquarters, sorrel, angelica, pokeweed, mustard greens, chickweed, cocklebur, chickweed, celery, sedge, lichen, water spinach, perilla, foxtail, crabgrass, ryegrass, false sorghum, barnyard grass, licorice, annual bluegrass, goosegrass, purslane, bulrush, sedge, foxtail grass, begonia, soapberry, sheep's hoof, plantain, black nightshade, and iron amaranth.

[0099] The organophosphorus compounds, their preparation methods, and applications according to the present invention are further illustrated below through examples. These examples are implemented based on the technical solutions of the present invention, providing detailed implementation methods and specific operating procedures; however, the scope of protection of the present invention is not limited to the following examples.

[0100] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods in the art. Unless otherwise specified, the experimental materials used in the following embodiments are commercially available.

[0101] Example 1

[0102] Preparation of compound 1

[0103] The preparation method of compound 1 comprises the following steps:

[0104] (1) Into a 100 mL three-necked round bottom flask, 10 mmol of dimethyl hydroxymethyl phosphonate (its structural formula is shown as formula (1)), 10 mmol of triethylamine and 20 mL of dichloromethane were sequentially added, the raw materials were dissolved by stirring, and the system was cooled to 0°C after being clarified;

[0105] (2) 10 mL of a dichloromethane solution of 3,6-dichloropyridine formyl chloride (its structural formula is shown as formula (2)) (wherein the molar amount of 3,6-dichloropyridine formyl chloride is 10 mmol) was slowly added dropwise to the above-mentioned mixed system under stirring. After the dropwise addition was completed, the reaction was continued to be stirred at 25°C, and the reaction progress was monitored by TLC. The reaction was ended after 2 h. Then the obtained material after the reaction was washed by saturated sodium bicarbonate solution, 5% dilute hydrochloric acid and saturated brine, the organic phase was washed to be neutral and combined, and then dried by anhydrous sodium sulfate, followed by suction filtration, and the yellow solid (compound 1) was obtained by desolventizing under reduced pressure, the yield of compound 1 was 81%, and the melting point was 52-53°C.

[0106] Compound 1 structural identification data: 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 8.23 (d, J = 8.6 Hz, 1H, Ar-H), 7.84 (d, J = 8.5 Hz, 1H, Ar-H), 4.84 (d, J = 8.6 Hz, 2H, CH2), 3.76 (d, J = 10.8 Hz, 6H, OCH3);

[0107] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 162.29 (d, J = 7.7 Hz), 148.63, 146.19, 143.04, 129.74, 129.22, 57.56 (d, J = 163.2 Hz), 53.62 (d, J = 6.1 Hz);

[0108] 31 P NMR (162 MHz, DMSO-d6) δ 20.42 (s);

[0109] HRMS (EI): calcd. For C9H 10 Cl2NO5P [M+H] + 313.97464, found: 313.97476.

[0110] Example 2

[0111] Preparation of compound 2

[0112] The preparation of compound 2 was carried out according to the method of example 1, except that dimethyl hydroxymethyl phosphonate was replaced by equimolar amount of dimethyl (1-hydroxyethyl) phosphonate (its structural formula is shown as formula (3)), to obtain colorless liquid (compound 2) with a yield of 84%.

[0113] Compound 2 structural identification data: 1 H NMR (600 MHz, DMSO-d6) δ (ppm): 8.23 (d, J = 8.6 Hz, 1H, Ar-H), 7.83 (d, J = 8.6 Hz, 1H, Ar-H), 5.55 (p, J = 7.2 Hz, 1H, CH), 3.76 (t, J = 10.1 Hz, 2x3H, OCH3), 1.51 (dd, J = 16.5, 7.2 Hz, 3H, CH3);

[0114] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 162.09 (d, J = 7.2 Hz), 148.69, 146.63, 143.02, 129.45, 129.15, 66.32 (d, J = 168.4 Hz), 54.50 (d, J = 6.8 Hz), 53.74 (d, J = 6.1 Hz), 15.34;

[0115] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 22.03 (s);

[0116] HRMS (ESI): calcd. for C 10 H 12 Cl2NO5P[M+H] + 327.99029, found: 327.99043.

[0117] Example 3

[0118] Preparation of compound 3

[0119] The preparation of compound 3 was carried out according to the method of example 1, except that dimethyl hydroxymethyl phosphonate was replaced by equimolar amount of dimethyl (2-furanyl(hydroxy)methyl) phosphonate (its structural formula is shown as formula (4)), to obtain white solid (compound 3) with a yield of 70% and a melting point of 79-80 °C.

[0120] Compound 3 structural identification data:1 H NMR (600 MHz, DMSO-d6) δ (ppm): 8.22 (d, J = 8.6 Hz, 1 H, Ar-H), 7.83 (d, J = 9.1 Hz, 2 H, Ar-H), 6.84 (s, 1 H, Ar-H), 6.69 (d, J = 14.6 Hz, 1 H, CH), 6.59 (s, 1 H, Ar-H), 3.84 (d, J = 10.7 Hz, 3 H, OCH3), 3.79 (d, J = 10.7 Hz, 3 H, OCH3);

[0121] 13 C NMR (151 MHz, DMSO-d6) δ (ppm): 161.62 (d, J = 7.5 Hz), 148.66, 146.05, 145.87, 145.31, 142.93, 129.59, 129.21, 113.41, 111.56, 64.73 (d, J = 173.5 Hz), 54.48 (d, J = 6.8 Hz), 54.19 (d, J = 6.3 Hz);

[0122] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 16.22 (s);

[0123] HRMS (ESI): calcd. for C 13 H 12 Cl2NO6P[M+H] + 379.98521, found: 379.98496.

[0124] Example 4

[0125] Preparation of compound 4

[0126] The preparation of compound 4 was carried out according to the method of Example 1, except that dimethylhydroxymethylphosphonate was replaced by equimolar amount of dimethyl(2-thienyl(hydroxy)methyl)phosphonate (its structural formula is shown as formula (5)), to obtain yellow solid (compound 4) with a yield of 58% and a melting point of 69-70 °C.

[0127] Compound 4 structural identification data: 1H NMR (400 MHz, DMSO-d6) d (ppm): 8.22 (d, J = 8.5 Hz, 1 H, Ar-H), 7.84 (d, J = 8.5 Hz, 1 H, Ar-H), 7.70 (d, J = 5.1 Hz, 1 H, Ar-H), 7.43 (s, 1 H, Ar-H), 7.11 (t, J = 4.3 Hz, 1 H, Ar-H), 6.87 (d, J = 13.3 Hz, 1 H, CH), 3.79 (d, J = 10.7 Hz, 3 H, OCH3), 3.71 (d, J = 10.6 Hz, 3 H, OCH3);

[0128] 13 C NMR (101 MHz, Chloroform-d) d (ppm): 161.69 (d, J = 8.7 Hz), 149.09, 146.26, 141.24, 133.48, 130.09, 129.65 (d, J = 7.9 Hz), 127.97 (d, J = 2.7 Hz), 127.90, 127.10 (d, J = 2.0 Hz), 67.41 (d, J = 177.7 Hz), 54.51 (d, J = 7.0 Hz), 54.29 (d, J = 6.5 Hz);

[0129] 31 P NMR (162 MHz, DMSO-d6) d (ppm): 17.28 (s);

[0130] HRMS (ESI): calcd. for C 13 H 12 Cl2NO5PS[M+H] + 395.96236, found: 395.96255.

[0131] Example 5

[0132] Preparation of compound 5

[0133] The preparation of compound 5 was carried out according to the method of Example 1, except that dimethylhydroxymethylphosphonate was replaced by equimolar amount of dimethyl(2-pyridyl(hydroxy)methyl)phosphonate (its structural formula is shown as formula (6)), to obtain yellow solid (compound 5) with a yield of 55% and a melting point of 71-72 °C.

[0134] Compound 5 structural identification data: 1H NMR (400 MHz, DMSO-d6) d (ppm): 8.62 (d, J = 4.9 Hz, 1H), 8.25 (d, J = 8.5 Hz, 1H), 7.92 (t, J = 7.7 Hz, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.44 (t, J = 6.4 Hz, 1H), 6.48 (d, J = 13.7 Hz, 1H), 3.76 (dd, J = 15.1, 10.7 Hz, 6H);

[0135] 13 C NMR (101 MHz, DMSO-d6) d (ppm): 161.80 (d, J = 10.3 Hz), 152.95, 149.74, 148.73, 145.95, 143.17, 137.77, 129.95, 129.45, 124.42, 122.95 (d, J = 4.0 Hz), 73.28 (d, J = 163.0 Hz), 54.62 (d, J = 6.7 Hz), 54.28 (d, J = 6.4 Hz);

[0136] 31 P NMR (162 MHz, DMSO-d6) d (ppm): 17.45 (s);

[0137] HRMS (ESI): calcd. for C 14 H 13 Cl2N2O5P[M+H] + 391.00119, found: 391.00159.

[0138] Example 6

[0139] Preparation of compound 6

[0140] The preparation method of compound 6 comprises the following steps:

[0141] (1) Into a 100 mL three-necked round-bottom flask, 10 mmol of (1-hydroxyethyl) cyclic phosphonic acid dimethyl ester (its structural formula is shown as formula (7)), 30 mmol of pyridine and 20 mL of tetrahydrofuran were sequentially added, the raw material was completely dissolved by stirring, and after the system was clarified, the mixed system was cooled to -10 °C;

[0142] (2) 10 mL of a solution of 3,6-dichloropyridinecarboxylic acid chloride (20 mmol) in tetrahydrofuran was slowly added dropwise to the above mixture under stirring. After the dropwise addition was completed, the reaction was continued under stirring at 50°C, and the progress of the reaction was monitored by TLC. The reaction was completed after 0.5 h. The reaction mixture was then washed with saturated sodium bicarbonate solution, 5% dilute hydrochloric acid and saturated brine until the organic phase was neutral, and the organic phase was combined and dried over anhydrous sodium sulfate, followed by suction filtration, and the white solid (compound 6) was obtained by desolventizing under reduced pressure. The yield of compound 6 was 87%, and the melting point was 81-82°C.

[0143] Structural identification data of compound 6: 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 8.24 (d, J = 8.6 Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 5.68 (p, J = 7.0 Hz, 1H), 4.42 (ddd, J = 14.1, 10.8, 3.3 Hz, 2H), 4.04 (dtd, J = 16.5, 11.0, 2.5 Hz, 2H), 1.52 (dd, J = 16.2, 7.0 Hz, 3H), 1.17 (s, 3H), 0.89 (s, 3H);

[0144] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 161.74 (d, J = 8.5 Hz), 148.53, 145.89, 143.27, 130.21, 129.39, 78.23 (d, J = 7.1 Hz), 77.48 (d, J = 6.9 Hz), 66.95 (d, J = 162.0 Hz), 32.57 (d, J = 8.0 Hz), 21.60, 20.10, 15.26;

[0145] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 11.21 (s);

[0146] HRMS (ESI): calcd for C 13 H 16 Cl2NO5P[M+H] + 391.00119, found: 391.00159.

[0147] Example 7

[0148] Preparation of compound 7

[0149] The preparation method of compound 7 comprises the following steps:

[0150] (1) Into a 100 mL three-necked round-bottom flask, 10 mmol of diethyl (1-hydroxyethyl) phosphonate (its structural formula is shown as formula (8)), 40 mmol of triethylamine and 20 mL of tetrahydrofuran were sequentially added, the raw materials were dissolved by stirring, and the system was cooled to 5°C after being clarified;

[0151] (2) 10 mL of a tetrahydrofuran solution of 3,6-dichloropyridine formyl chloride (wherein the molar amount of 3,6-dichloropyridine formyl chloride is 30 mmol) was slowly added dropwise to the above-mentioned mixed system under stirring. After the dropwise addition was completed, the reaction was continued under stirring at 10°C, and the reaction progress was monitored by TLC, and the reaction was ended after 5 h. Then the obtained material after the reaction was washed by saturated sodium bicarbonate solution, 5% dilute hydrochloric acid and saturated brine, the organic phase was washed to neutral and combined, and then dried by anhydrous sodium sulfate, followed by suction filtration, and white solid (compound 7) was obtained by desolventizing under reduced pressure, the yield of compound 7 was 85%, and the melting point was 93-94°C.

[0152] Compound 7 structural identification data: 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 8.23 (d, J = 8.6 Hz, 1H), 7.83 (d, J = 8.6 Hz, 1H), 5.48 (p, J = 7.1 Hz, 1H), 4.13 (h, J = 7.0 Hz, 4H), 1.50 (dd, J = 16.3, 7.0 Hz, 3H), 1.26 (td, J = 7.0, 3.1 Hz, 6H);

[0153] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 162.09 (d, J = 7.5 Hz), 148.66, 146.65, 142.98, 129.40, 129.10, 67.49, 65.81, 63.28 (d, J = 6.8 Hz), 63.03 (d, J = 6.2 Hz), 16.74 (t, J = 5.4 Hz), 15.33;

[0154] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 19.52;

[0155] HRMS (ESI): calcd. for C 12 H 16 Cl2NO5P[M+H] + 368.0216, found: 368.0212.

[0156] Example 8

[0157] Preparation of compound 8

[0158] (1) Into a 100 mL three-necked round-bottom flask, dimethylhydroxymethyl phosphonate (10 mmol), triethylamine (50 mmol) and 20 mL of dichloromethane were sequentially added, the raw material was completely dissolved by stirring, and the system was clarified. After cooling to 10 °C, the mixed system was cooled to 10 °C;

[0159] (2) 10 mL of 3,5,6-trichloropyridine acetyl chloride (its structural formula is shown in formula (9)) in tetrahydrofuran solution (wherein the molar amount of 3,5,6-trichloropyridine acetyl chloride is 40 mmol) was slowly added to the above mixed system under stirring. After the addition was completed, the reaction was continued at 30 °C under stirring, and the reaction progress was monitored by TLC. After 3 h of reaction, the reaction was ended. Then the obtained material after reaction was washed with saturated sodium bicarbonate solution, 5% dilute hydrochloric acid and saturated brine, the organic phase was washed to neutral and combined, and then dried with anhydrous sodium sulfate, followed by suction filtration, and white solid (compound 8) was obtained by desolventizing under reduced pressure. The yield of compound 8 was 90%, and the melting point was 65-66 °C.

[0160] Structure identification data of compound 8: 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 8.50 (s, 1H, Ar-H), 5.18 (s, 2H, CH2), 4.62 (d, J = 8.6 Hz, 2H, CH2), 3.72 (d, J = 10.8 Hz, 6H, OCH3);

[0161] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 167.53 (d, J = 7.9 Hz), 155.77, 142.65, 141.79, 122.52, 117.03, 64.00, 56.43 (d, J = 164.0 Hz), 53.46 (d, J = 6.0 Hz);

[0162] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 20.68 (s);

[0163] HRMS (ESI): calcd. for C 10 H 11 Cl3NO6P[M+H] + 377.94623, found: 377.94678.

[0164] Example 9

[0165] Preparation of compound 9

[0166] The preparation of compound 9 was carried out according to the method of Example 8, except that dimethyl hydroxymethyl phosphonate was replaced by equimolar amount of dimethyl (1-hydroxyethyl) phosphonate to obtain a white solid (compound 9) with a yield of 87% and a melting point of 67-68 °C.

[0167] Structural identification data of compound 9: 1 H NMR (600 MHz, DMSO-d6) δ (ppm): 8.47 (s, 1H, Ar-H), 5.28 (p, J = 7.4 Hz, 1H, CH), 5.11 (q, J = 16.2 Hz, 2H, CH2), 3.71 (d, J = 10.5 Hz, 3H, OCH3), 3.67 (d, J = 10.6 Hz, 3H, OCH3), 1.37 (dd, J = 16.5, 7.1 Hz, 3H, CH3);

[0168] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 167.27 (d, J = 7.9 Hz), 155.81, 142.57, 141.88, 122.50, 117.01, 65.76, 64.19 (d, J = 21.3 Hz), 53.90 (d, J = 6.7 Hz), 53.55 (d, J = 6.3 Hz), 15.29;

[0169] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 22.39 (s);

[0170] HRMS (ESI): calcd. for C 11 H 13 Cl3NO6P [M+H] + 391.96188, found: 391.96106.

[0171] Example 10

[0172] Preparation of compound 10

[0173] The preparation of compound 10 was carried out according to the method of Example 8, except that dimethyl hydroxymethyl phosphonate was replaced by equimolar amount of dimethyl (2-furanyl(hydroxy)methyl) phosphonate to obtain a yellow solid (compound 10) with a yield of 86% and a melting point of 77-78 °C.

[0174] Structural identification data of compound 10: 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 8.46 (s, 1H, Ar-H), 7.73 (s, 1H, Ar-H), 6.64 (s, 1H, Ar-H), 6.50 (s, 1H, Ar-H), 6.36 (d, J = 14.8 Hz, 1H, CH), 5.16 (s, 2H, CH2), 3.74 (d, J = 10.7 Hz, 3H, OCH3), 3.66 (d, J = 10.8 Hz, 3H, OCH3);

[0175] 13 C NMR (101 MHz, CDC13-d) δ (ppm): 166.47 (d, J = 7.6 Hz), 155.35, 145.53, 144.21, 143.16, 140.59, 123.11, 117.15, 112.77 (d, J = 6.3 Hz), 111.05, 63.66 (d, J = 177.8 Hz), 63.47, 54.18 (d, J = 6.9 Hz), 54.03 (d, J = 6.3 Hz);

[0176] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 16.48 (s);

[0177] HRMS (ESI): calcd. for C 14 H 13 Cl3NO7P [M + H] + 443.95680, found: 443.95679.

[0178] Example 11

[0179] Preparation of compound 11

[0180] The preparation process of compound 11 was carried out according to the method of Example 8, except that dimethyl hydroxymethyl phosphonate was replaced by equimolar amount of (2-thienyl(hydroxy)methyl) dimethyl phosphonate, to obtain a yellow solid (compound 11) with a yield of 91% and a melting point of 91-92°C.

[0181] Structural identification data of compound 11: 1H NMR (400 MHz, DMSO-d6) d (ppm): 8.45 (s, 1 H, Ar-H), 7.62 (d, J = 5.1 Hz, 1 H, Ar-H), 7.26 (s, 1 H, Ar-H), 7.04 (t, J = 4.4 Hz, 1 H, Ar-H), 6.58 (d, J = 13.4 Hz, 1 H, CH), 5.18 (s, 2 H, CH2), 3.73 (d, J = 10.6 Hz, 3 H, OCH3), 3.64 (d, J = 10.6 Hz, 3 H, OCH3);

[0182] 13 C NMR (101 MHz, CDC13-d) d (ppm): 166.38 (d, J = 8.1 Hz), 155.33, 143.18, 140.57, 133.61, 129.33 (d, J = 7.9 Hz), 127.82 (d, J = 2.6 Hz), 127.10 (d, J = 1.0 Hz), 123.10, 117.13, 66.24 (d, J = 177.8 Hz), 63.53, 54.17 (dd, J = 6.8, 4.3 Hz);

[0183] 31 P NMR (162 MHz, DMSO-d6) d (ppm): 17.46 (s);

[0184] HRMS (ESI): calcd. for C 14 H 13 Cl3NO6PS [M + H] + 459.93395, found: 459.93390.

[0185] Example 12

[0186] Preparation of compound 12

[0187] The preparation of compound 12 was carried out according to the method of Example 8, except that dimethylhydroxymethylphosphonate was replaced by equimolar amount of dimethyl(2-pyridyl(hydroxy)methyl)phosphonate to give a colorless liquid (compound 12) with 85% yield.

[0188] Structural identification data of compound 12: 1H NMR (400 MHz, DMSO-d6) d (ppm): 8.57 (d, J = 4.9 Hz, 1H), 8.48 (s, 1H), 7.86 (td, J = 7.8, 1.8 Hz, 1H), 7.50-7.34 (m, 2H), 6.22 (d, J = 13.9 Hz, 1H), 5.28 (s, 2H), 3.74 (d, J = 10.7 Hz, 3H), 3.68 (d, J = 10.7 Hz, 3H);

[0189] 13 C NMR (101 MHz, Chloroform-d) d (ppm): 166.46 (d, J = 9.3 Hz), 155.32, 152.61, 149.43, 143.07, 140.58, 137.10, 123.64, 123.07, 122.44 (d, J = 4.0 Hz), 117.14, 72.02 (d, J = 166.5 Hz), 63.52, 54.15 (d, J = 6.9 Hz), 53.95 (d, J = 6.2 Hz);

[0190] 31 P NMR (162 MHz, DMSO-d6) d (ppm): 17.73 (s);

[0191] HRMS (ESI): calcd. for C 15 H 14 Cl3N2O6P[M + H] + 454.97278, found: 454.97281.

[0192] Example 13

[0193] Preparation of compound 13

[0194] The preparation of compound 13 was carried out according to the method of Example 8, except that dimethylhydroxymethylphosphonate was replaced by equimolar amount of dimethyl(1-hydroxyethyl)cyclic phosphonate to obtain white solid (compound 13) with a yield of 88% and a melting point of 88-89 °C.

[0195] Structural identification data of compound 13: 1H NMR (400 MHz, DMSO-d6) d (ppm): 8.50 (s, 1H), 5.52 (p, J = 6.9 Hz, 1H), 5.15 (s, 2H), 4.24 (ddd, J = 38.4, 10.8, 3.9 Hz, 2H), 4.09 - 3.93 (m, 2H), 1.38 (dd, J = 16.3, 7.0 Hz, 3H), 1.16 (s, 3H), 0.89 (s, 3H);

[0196] 13 C NMR (101 MHz, DMSO-d6) d (ppm): 167.37 (d, J = 8.4 Hz), 155.83, 142.58, 141.95, 122.55, 116.99, 77.97 (d, J = 6.9 Hz), 77.23 (d, J = 6.6 Hz), 64.86 (d, J = 162.6 Hz), 64.45, 32.47 (d, J = 7.7 Hz), 21.57, 20.20, 15.16;

[0197] 31 P NMR (162 MHz, DMSO-d6) d (ppm): 11.96 (s);

[0198] HRMS (ESI): calcd. for C 14 H 17 Cl3NO6P [M+H] + 431.9932, found: 431.9933.

[0199] Example 14

[0200] Preparation of compound 14

[0201] The preparation of compound 14 was carried out according to the method of Example 8, except that dimethylhydroxymethylphosphonate was replaced by equimolar amount of diethyl (1-hydroxyethyl)phosphonate to give a colorless liquid (compound 14) with 82% yield.

[0202] Structural identification data of compound 14: 1 H NMR (600 MHz, DMSO-d6) d (ppm): 8.48 (s, 1H), 5.21 (p, J = 7.2 Hz, 1H), 5.15 - 5.05 (m, 2H), 4.04 (dp, J = 14.8, 7.4 Hz, 4H), 1.35 (dd, J = 16.3, 7.0 Hz, 3H), 1.22 (dt, J = 11.6, 7.0 Hz, 6H);

[0203] 13C NMR (101 MHz, DMSO-d6) d (ppm): 167.24 (d, J = 8.1 Hz), 155.77, 142.50, 141.81, 122.42, 116.97, 66.12, 64.44, 64.20, 62.99 (d, J = 6.8 Hz), 62.75 (d, J = 6.1 Hz), 16.66 (dd, J = 8.2, 5.3 Hz), 15.21;

[0204] 31 P NMR (162 MHz, DMSO-d6) d (ppm): 19.91 (s);

[0205] HRMS (ESI): calcd for C 13 H 17 Cl3NO6P[M+H] + 419.99318, found: 419.99325.

[0206] Test Example

[0207] Test Example 1

[0208] Primary screening test of compound 1 to compound 14 against weed inhibition activity.

[0209] Test material: broad-leaved (dicotyledonous) weeds: Amaranthus retroflexus, Abutilon theophrasti, Eclipta prostrata; grasses (monocotyledonous) weeds: Setaria viridis, Digitaria sanguinalis, Echinochloa crus-galli.

[0210] Herbicidal activity primary screening test method: post-emergence stem and leaf spray treatment, test weeds are Echinochloa crus-galli, Digitaria sanguinalis, Setaria viridis, Abutilon theophrasti, Amaranthus retroflexus, Eclipta prostrata.

[0211] A certain amount of technical material (compound 1 to compound 14) was weighed with an analytical balance (0.0001 g), first dissolved in DMF to prepare a 1.0% stock solution, then diluted with distilled water containing 0.1% Tween-80 for standby. Take a flowerpot with an inner diameter of 7.5 cm, fill the composite nutrient soil to 3 / 4 of the flowerpot, directly sow the above six kinds of weeds (germination rate ≥ 85%), cover the soil with 0.2 cm, add water at the bottom to make the soil saturated, then place it in the greenhouse for growth, keep the soil moisture content appropriate, and wait until the weeds grow to about 3 leaves for standby. After the automatic spray tower (model: 3WPSH-700E) is applied with each compound (compound 1 to compound 14) at a dose of 450, 150 g a.i. / ha, the weeds are moved into the greenhouse for culture after the leaf surface of the weeds is dried, and the activity (%) against weeds is investigated after 25 days, the results are expressed in growth inhibition rate (%), and the results are shown in Table 1.

[0212] Table 1: Screening results of the inhibitory activity of compounds 1-14 against broadleaf weeds (growth inhibition rate %) - post-emergence foliar spray treatment (25 days after application)

[0213] Table 2: Screening results of the inhibitory activity of compound 8-14 against grassy weeds (growth inhibition rate %) - post-emergence foliar spray treatment (25 days after application)

[0214] As shown in Tables 1 and 2, compounds 1 to 14 tested in this invention exhibited moderate to highly effective inhibitory activity against the tested weeds at concentrations of 450 and 150 g.i. / ha. Compounds 8, 9, 11, and 14 showed highly effective inhibitory activity against broadleaf weeds (velvetleaf, amaranth, and edelweiss), with inhibition rates of 80–100%, comparable to the control herbicide Clacyfos. Compounds 8, 11, 12, and 14 showed significant inhibitory activity against gramineous weeds (barnyardgrass and crabgrass), with inhibition rates of 75–95%, and also showed some inhibitory activity against foxtail grass (40–70%), with all activities significantly superior to the control herbicide Clacyfos. In particular, compounds 8, 11, and 14 showed excellent inhibitory activity against both broadleaf and gramineous weeds, indicating that the organophosphorus compounds described in this invention can effectively control the growth of broadleaf and gramineous weeds post-emergence.

[0215] Test Example 2

[0216] Herbicidal spectrum test of highly active compounds

[0217] Experimental materials: Broadleaf (dicotyledonous) weeds: Xanthium sibiricum, Amaranth, Cassia tora, Mustard greens, Abutilon theophrasti, Alfalfa, Orychophragmus violaceus, Morning glory, Alternanthera philoxeroides, Veronica persica, Portulaca oleracea, Eriocaulon buergerianum, Lamb's quarters, Rumex japonicus, Eclipta prostrata, Phytolacca acinosa, Bidens pilosa, Capsella bursa-pastoris, Chickweed, Cressida albicans, Lepidium apetalum, Erigeron brevis, Alternanthera philoxeroides, Perilla frutescens;

[0218] Grass (monocot) weeds: foxtail grass, crabgrass, ryegrass, false sorghum, barnyard grass, nitrifying grass, wild oats, Kentucky bluegrass, goosegrass, purslane, sedge, foxtail grass.

[0219] Herbicidal spectrum test method: A certain amount of technical material was weighed by an analytical balance (0.0001 g), dissolved in DMF to prepare a 1.0% stock solution, and then diluted with 0.1% Tween-80 distilled water for standby. An inner diameter of 7.5 cm flowerpot was used, and composite nutrient soil was filled to 3 / 4 of the flowerpot, and crop seeds (germination rate ≥ 85%) were directly sown, covered with soil, and water was added to keep the soil moist. When the weeds grew to 3-4 leaf stage, they were ready for use. After the test compound was applied at a dose of 450 g a.i. / ha in an automatic spray tower (model: 3WPSH-700E), it was moved into a greenhouse for culture, and after 25 days, the results were observed by visual inspection. The results were expressed as growth inhibition rate (%), and the results are shown in Tables 3, 4 and 5.

[0220] Table 3: High-activity compound herbicidal spectrum test results - broadleaf weed spectrum, (growth inhibition rate %) - post-emergence stem and leaf spray treatment (25 days after treatment)

[0221] Table 4: High-activity compound herbicidal spectrum test results - broadleaf weed spectrum, (growth inhibition rate %) - post-emergence stem and leaf spray treatment (25 days after treatment)

[0222] Table 5: High-activity compound herbicidal spectrum test results - gramineous weed spectrum (growth inhibition rate %) - post-emergence stem and leaf spray treatment (25 days after treatment)

[0223] According to the results in Tables 3 and 4, the inhibition activities of compound 2, compound 3, compound 6, compound 8, compound 9, compound 10, compound 11, compound 13 and compound 14 against the tested broadleaf weeds are comparable to glyphosate, and the inhibition activities of compound 2, compound 3, compound 6, compound 8, compound 9, compound 10, compound 11, compound 13 and compound 14 against broadleaf weeds such as velvetleaf and cleavers are even better than glyphosate, confirming that these compounds show excellent activity in post-emergence control of broadleaf weeds.

[0224] According to the results in Table 5, compound 8, compound 9, compound 10, compound 11, compound 13 and compound 14 also have significant inhibition activities against gramineous weeds, and the inhibition activities of compound 9, compound 10 and compound 13 against elephant's ear are higher than glyphosate, so the organic phosphine compounds described in the present application have significant research significance as a non-selective herbicide or a lead structure, and are worth further research and promotion.

[0225] Example 15

[0226] Preparation of compound 15

[0227] The preparation method of compound 15 comprises the following steps:

[0228] (1) Into a 50 mL three-necked round-bottom flask, 4.5 mmol of trichloropyridineoxalic acid (its structural formula is shown in formula (10)) and 10 mL of tetrahydrofuran were sequentially added, and the system was cooled to 0 °C in an ice bath, and then 2 mL of a tetrahydrofuran solution of carbonyldiimidazole (the amount of substance of carbonyldiimidazole was 4.95 mmol) was added dropwise into the round-bottom flask. Then the system was moved to 25 °C for reaction for 20 min, and the stirring was turned off.

[0229] (2) Into the material obtained in step (1), 0.23 mmol of 4-N,N-dimethylpyridine (DMAP) and 4.5 mmol of (1-hydroxyethyl)dimethyl phosphine oxide (its structural formula is shown in formula (11)) were added, and the system was heated to 60 °C for reaction for 6 h, and then the reaction was monitored by TLC, and the heating was turned off. The obtained material was cooled, washed and dried to obtain a white solid, and the yield was 87.2%, and the melting point (m.p.) was 130-131 °C.

[0230] The structure identification data of the compound 15 product are as follows: 1H NMR (600 MHz, CDCl3) δ (ppm): 7.80 (s, 1H, Ar-H), 5.34 (s, 1H, CH), 4.97 (dd, J = 72.0, 36.0 Hz, 2H, CH2), 1.65-1.40 (m, 3x3H, CH3);

[0231] 13C NMR (101 MHz, CDCl3) δ (ppm): 166.91, 155.41, 143.13, 140.77, 123.31, 117.22, 69.10 (d, J = 79.4 Hz), 63.74, 14.43 (d, J = 71.2 Hz), 13.57, 12.33 (d, J = 61.6 Hz);

[0232] 31P NMR (162 MHz, DMSO-d6) δ (ppm): 39.80;

[0233] HRMS (ESI): calcd. for Chemical Formula: C11H13Cl3NO4P [M+H] + 359.97205, found: 359.97124.

[0234] Example 16

[0235] Preparation of compound 16

[0236] The preparation method of compound 16 was carried out according to the method of example 15, except that (1-hydroxyethyl)dimethyl phosphine oxide was replaced by equimolar (1-hydroxypropyl)dimethyl phosphine oxide (its structural formula is shown as formula (12)).

[0237] The obtained pure product was white solid, with a yield of 82.5% and a melting point (m.p.) of 131-132°C.

[0238] The structural identification data of compound 16 product: 1 H NMR (400 MHz, CDCl3) δ (ppm): 7.85 (s, 1H, Ar-H), 5.31 (d, J = 11.0 Hz, 1H, CH), 5.17-4.92 (m, 2H, CH2), 2.00 (d, J = 112.0 Hz, 2H), 1.65-1.43 (m, 2x3H, CH3), 1.09 (t, J = 7.3 Hz, 3H, CH3);

[0239] 13 C NMR (101 MHz, CDCl3) δ (ppm): 167.34, 155.40, 143.14, 140.78, 123.33, 117.26, 73.76 (d, J = 82.82 Hz), 63.41, 21.50, 14.7 (d, J = 66.66 Hz), 12.65 (d, J = 68.68 Hz), 10.59 (d, J = 10.1 Hz);

[0240] 31 P NMR (162 MHz, CDCl3) δ (ppm): 43.89;

[0241] HRMS (ESI): calcd. for Chemical Formula: C 12 H 15 C l3 NO4P [M+H] + 373.9877, found: 373.98775.

[0242] Example 17

[0243] Preparation of compound 17

[0244] The preparation method of compound 17 was carried out according to the method of example 15, except that (1-hydroxyethyl)dimethyl phosphine oxide was replaced by equimolar (1-hydroxypropyl)dimethyl phosphine oxide (its structural formula is shown as formula (12)).

[0245] The obtained pure product was white solid with a yield of 88.4% and a melting point (m.p.) of 127-128 °C.

[0246] Structure identification data of compound 17 product: 1 H NMR (400 MHz, CDC13) δ (ppm): 7.83 (s, 1H, Ar-H), 5.39 (d, J = 11.1 Hz, 1H, CH), 5.02 (dd, J = 31.7, 16.8 Hz, 2H, CH2), 1.91 (d, J = 80.0 Hz, 2H, CH2), 1.61-1.32 (m, 2+2x3H, CH2, CH3), 0.99 (t, J = 4.0 Hz, 3H, CH3);

[0247] 13 C NMR (101 MHz, CDC13) δ (ppm): 167.24, 155.42, 143.14, 140.78, 123.34, 117.26, 72.04 (d, J = 82.82 Hz), 63.43, 29.89, 19.18 (d, J = 10.1 Hz), 14.63 (d, J = 68.3 Hz), 13.49, 12.57 (d, J = 67.3 Hz);

[0248] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 38.95;

[0249] HRMS (ESI): calcd. for Chemical Formula: C 13 H 17 Cl3NO4P [M+H] + 388.00335, found: 388.00329.

[0250] Example 18

[0251] Preparation of compound 18

[0252] The preparation method of compound 18 comprises the following steps:

[0253] (1) Into a 50 mL three-necked round-bottom flask, 5.4 mmol of trichloropyridineoxalic acid and 10 mL of acetonitrile were sequentially added, and the system was ice-bathed to -5 °C. Then, 2 mL of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide acetonitrile solution (the amount of substance of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide was 5.4 mmol) was added dropwise into the round-bottom flask. Then, the system was moved to 40 °C for reaction for 5 min, and the stirring was stopped.

[0254] (2) To the material obtained in step (1), 0.45 mmol of 1-hydroxybenzotriazole (HOBt) and 4.5 mmol of 1-[(4-chlorophenyl)hydroxymethyl]dimethylphosphine oxide (its structural formula is shown as formula (14)) were added, and heated to 80°C for 3h after TLC monitoring reaction was completed, the heating was turned off. The resulting material was cooled, washed, dried to obtain white solid, yield 80.6%, melting point (m.p.) 174-175°C.

[0255] Compound 18 product structure identification data: 1 H NMR (600 MHz, DMSO-d6) δ (ppm): 8.41 (s, 1H, Ar-H), 7.41 (d, J = 8.3 Hz, 2H, Ar-H), 7.33 (d, J = 7.9 Hz, 2H, Ar-H), 6.13 (d, J = 5.0 Hz, 1H, CH), 5.21 (s, 2H, CH2), 1.37 (d, J = 13.2 Hz, 2x3H, CH3);

[0256] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 167.43 (d, J = 6.9 Hz), 155.77, 142.54, 141.88 (d, J = 5.3 Hz), 133.43, 132.94, 129.37, 128.72, 122.53, 116.95, 73.87 (d, J = 77.1 Hz), 64.38, 14.01 (d, J = 68.9 Hz), 13.09 (d, J = 68.4 Hz);

[0257] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 40.64;

[0258] HRMS (ESI): calcd. for Chemical Formula: C 16 H 14 Cl4NO4P[M+H] + 455.9487, found: 455.9471.

[0259] Example 19

[0260] Preparation of compound 19

[0261] The preparation method of compound 19 was carried out according to the method of example 18, except that 1-[(4-chlorophenyl)hydroxymethyl]dimethylphosphine oxide was replaced by equimolar amount of 1-[(phenyl)hydroxymethyl]dimethylphosphine oxide (its structural formula is shown as formula (15)).

[0262] The obtained pure product was white solid with a yield of 84.3% and a melting point (m.p.) of 169-170°C.

[0263] The structural identification data of compound 19 product: 1 H NMR (600 MHz, DMSO-d6) δ (ppm): 8.44 (s, 1H, Ar-H), 7.49-7.17 (m, 5H, Ar-H), 6.09 (d, J = 6.0 Hz, 1H, CH), 5.22 (s, 2H, CH2), 1.35 (t, J = 12.0 Hz, 6H, CH3);

[0264] 13 C NMR (151 MHz, DMSO-d6) δ (ppm): 167.29 (d, J = 7.4 Hz), 155.65, 142.43, 141.72 (d, J = 3.7 Hz), 133.72, 128.50, 127.29 (d, J = 3.5 Hz), 122.35, 116.82, 74.41 (d, J = 77.9 Hz), 64.19, 13.85 (d, J = 68.9 Hz), 12.92 (d, J = 68.4 Hz);

[0265] 31 P NMR (162 MHz, CDCl3) δ (ppm): 42.57;

[0266] HRMS (ESI): calcd. for Chemical Formula: C 16 H 15 Cl3NO4P[M+H] + 421.9877, found: 421.9872.

[0267] Example 20

[0268] Preparation of compound 20

[0269] The preparation method of compound 20 includes the following steps:

[0270] (1) Into a 50 mL three-necked round-bottom flask, 4.95 mmol of 2,4-dichlorophenoxyacetic acid and 10 mL of dichloromethane were sequentially added, and the flask was ice-bathed to -2 °C, followed by dropwise addition of 2 mL of a dichloromethane solution of dicyclohexylcarbodiimide (the amount of substance of dicyclohexylcarbodiimide was 4.5 mmol) into the round-bottom flask. Then, the system was moved to 10 °C for reaction for 30 min, and the stirring was turned off.

[0271] (2) Into the material obtained in step (1), 0.32 mmol of 4-N,N-dimethylpyridine (DMAP) and 4.5 mmol of 1-[(thienyl)hydroxymethyl]dimethylphosphine oxide (its structural formula is shown as formula (16)) were added, and after heating to 20 °C for reaction for 10 h, the reaction was completed as monitored by TLC, and the heating was turned off. The obtained material was cooled, washed, and dried to obtain a white solid, with a yield of 81.3% and a melting point (m.p.) of 60-61 °C.

[0272] Product structure identification data of compound 20: 1 H NMR (400 MHz, CDC13) δ (ppm): 7.37 (d, J = 5.0 Hz, 1H, Ar-H), 7.22 (s, 1H, Ar-H), 7.17 (dd, J = 7.9, 2.8 Hz, 1H, Ar-H), 7.09-7.03 (m, 1H, Ar-H), 6.98-6.87 (m, 1H, Ar-H), 6.87-6.80 (m, 1H, Ar-H), 6.45 (d, J = 5.7 Hz, 1H, CH), 4.80 (dd, J = 28, 16 Hz, 2H), 1.54 (dd, J = 12.4, 8.2 Hz, 6H, CH3);

[0273] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 168.00 (d, J = 6.9 Hz), 156.61 (d, J = 240.5 Hz), 150.14 (d, J = 2.5 Hz), 135.42, 128.58 (d, J = 5.6 Hz), 128.02, 127.42, 122.46 (d, J = 10.8 Hz), 117.84 (d, J = 26.4 Hz), 115.31-114.96 (m), 114.87, 70.79 (d, J = 80.9 Hz), 65.96, 14.39, 13.70, 13.02;

[0274] 31 P NMR (162 MHz, CDC13) δ (ppm): 42.72;

[0275] HRMS (ESI): calcd. for Chemical Formula: C 15 H 15 Cl2NO4PS[M+Na] + 414.96979, found: 414.97041.

[0276] Example 21

[0277] Preparation of compound 21

[0278] The preparation of compound 21 was carried out according to the method of example 20, except that 2,4-dichlorophenoxyacetic acid was replaced by equimolar amount of 2-methyl-4-chlorophenoxyacetic acid.

[0279] The obtained pure product was white solid with a yield of 89.2% and a melting point (m.p.) of 83-84 °C.

[0280] Structural identification data of compound 21 product: 1 H NMR (600 MHz, CDC13) δ (ppm): 7.36 (d, J = 4.3 Hz, 1H, Ar-H), 7.20 (s, 1H, Ar-H), 7.14 (s, 1H, Ar-H), 7.05 (d, J = 8.7 Hz, 2H, Ar-H), 6.57 (d, J = 8.6 Hz, 1H, Ar-H), 6.42 (d, J = 4.7 Hz, 1H, CH), 4.75 (q, J = 16.4 Hz, 2H, CH2), 2.25 (s, 3H, CH3), 1.48 (t, J = 12.0 Hz, 2x3H, CH3);

[0281] 13 C NMR (101 MHz, DMSO-d6) δ (ppm): 168.33 (d, J = 6.06 Hz), 154.87, 135.46, 130.59, 129.01, 128.55, 127.95, 127.36, 126.71, 125.08, 113.49, 70.64 (d, J = 80.8 Hz), 65.38, 16.21, 13.67 (d, J = 139.38 Hz), 13.66;

[0282] 31 P NMR (162 MHz, CDC13) δ (ppm): 42.92;

[0283] HRMS (ESI): calcd. for Chemical Formula: C 16 H 18Cl2ClO4PS[M+H] + 373.0427, found: 373.04207.

[0284] Example 22

[0285] Preparation of compound 22

[0286] Compound 22 was prepared according to the method of Example 20, except that 2,4-dichlorophenoxyacetic acid was replaced with an equal amount of 2-chloro-4-fluorophenoxyacetic acid.

[0287] The obtained pure product is a white solid with a yield of 89.4% and a melting point (mp) of 135-136℃.

[0288] Structural identification data of compound 22: 1 H NMR (400MHz, DMSO-d6) δ (ppm): 7.61 (s, 2H, Ar-H), 7.34 (dd, J=8.8, 2.0Hz, 1H, Ar-H), 7.22 (s, 1H), 7.11 (d, J=8.0Hz, 1H, Ar-H), 7 .07(t,J=4.0Hz,1H,Ar-H),6.44(d,J=5.2Hz,1H,CH),5.16(dd,J=43.9,16.9Hz,2H,CH2),1.42(dd,J=27.5,13.2Hz,2×3H,CH3);

[0289] 13 C NMR (151MHz, DMSO-d6)δ (ppm): 13 C NMR (101MHz, DMSO-d6) δ (ppm): 167.83 (d, J = 6.8Hz), 152.47, 135.37 (d, J = 1.8Hz), 130.01, 128.60 (d, J = 5.6Hz) ,128.41,128.04,127.41,125.78,122.90,115.50,70.83(d,J=80.8Hz),65.74,13.72(d,J=137.36Hz),13.72;

[0290] 31 P NMR (162MHz, DMSO-d6) δ (ppm): 40.65;

[0291] HRMS(ESI):calcd.for Chemical Formula:C 16 H 18Cl2ClO4PS[M+K]+ 414.97328, found: 414.96982.

[0292] Example 23

[0293] Preparation of compound 23

[0294] The preparation method of compound 23 was carried out according to the method of example 20, except that 2,4-dichlorophenoxyacetic acid was replaced by equimolar 4-chlorophenoxyacetic acid.

[0295] The obtained pure product was white solid with a yield of 88.8% and a melting point (m.p.) of 132-133℃.

[0296] Structural identification data of compound 23 product: 1 H NMR (400 MHz, DMSO-d6) δ (ppm): 7.61 (d, J = 5.1 Hz, 1H, Ar-H), 7.32 (d, J = 8.7 Hz, 2H, Ar-H), 7.22 (s, 1H, Ar-H), 7.07 (t, J = 4.0, 1H, Ar-H), 6.97 (d, J = 8.8 Hz, 2H, Ar-H), 6.44 (d, J = 4.9 Hz, 1H, CH), 5.01 (dd, J = 46.9, 17.0 Hz, 2H, CH2), 1.41 (dd, J = 27.2, 13.2 Hz, 2x3H, CH3);

[0297] 13 C NMR (151 MHz, DMSO-d6) δ (ppm): 168.28 (d, J = 7.55 Hz), 156.68, 135.37, 129.67, 128.57 (d, J = 4.53 Hz), 127.98, 127.33, 125.49, 116.76, 70.87, 70.33, 65.08, 13.99 (d, J = 68.9 Hz), 13.36 (d, J = 68.0 Hz);

[0298] 31 P NMR (162 MHz, CDCl3) δ (ppm): 41.77;

[0299] HRMS (ESI): calcd. for Chemical Formula: C 15 H 16 ClO4PS[M+H] + 359.02682, found: 359.02664.

[0300] Example 24

[0301] Preparation of compound 24

[0302] The preparation method of compound 24 was carried out according to the method of Example 15, except that (1-hydroxyethyl)dimethylphosphine oxide was replaced by 1-[(thienyl)hydroxymethyl]dimethylphosphine oxide in equal amount.

[0303] The obtained pure product was white solid with a yield of 89.4% and a melting point (m.p.) of 53-55°C.

[0304] Structural identification data of compound 24 product: 1 H NMR (600 MHz, CDCl3) δ (ppm): 7.77 (s, 1H, Ar-H), 7.36 (s, 1H, Ar-H), 7.24 (s, 1H, Ar-H), 7.04 (s, 1H, Ar-H), 6.41 (s, 1H, CH), 5.03 (dd, J = 102.0, 18.0 Hz, 2H, CH2), 1.54 (t, J = 11.6 Hz, 2x3H, CH3);

[0305] 13 C NMR (101 MHz, CDCl3) δ (ppm): 166.70 (d, J = 5.05 Hz), 155.36, 143.20, 140.74, 133.62, 128.43 (d, J = 5.0 Hz), 127.39, 127.28, 123.32, 117.24, 70.79 (d, J = 82.3 Hz), 63.63, 14.25 (d, J = 69.7 Hz), 13.39 (d, J = 69.3 Hz);

[0306] 31 P NMR (162 MHz, CDCl3) δ (ppm): 42.18;

[0307] HRMS (ESI): calcd. for Chemical Formula: C 14 H 13 Cl3NO4PS [M+H] + 427.94412, found: 427.94328.

[0308] Example 25

[0309] Preparation of compound 25

[0310] The preparation method of compound 25 was carried out according to the method of example 15, except that (1-hydroxyethyl)dimethylphosphine oxide was replaced by equimolar amount of 1-[(furyl)hydroxymethyl]dimethylphosphine oxide (its structural formula is shown as formula (17)).

[0311] The obtained pure product was white solid with a yield of 86.9% and a melting point (m.p.) of 115-116°C.

[0312] The structural identification data of compound 25 product: 1 H NMR (400 MHz, CDCl3) δ (ppm): 7.77 (d, J = 2.2 Hz, 1H, Ar-H), 7.45 (s, 1H, Ar-H), 6.61 (s, 1H, Ar-H), 6.41 (s, 1H, Ar-H), 6.26 (d, J = 7.2 Hz, 1H, CH), 5.01 (dd, J = 58.7, 16.0 Hz, 2H, CH2), 1.63 (s, 2x3H, CH3);

[0313] 13 C NMR (101 MHz, CDCl3) δ (ppm): 166.65 (d, J = 5.9 Hz), 155.34, 145.62 (d, J = 2.5 Hz), 144.24 (d, J = 2.02 Hz), 143.16, 140.69, 123.25, 117.19, 113.07 (d, J = 5.1 Hz), 111.11, 67.74 (d, J = 83.3 Hz), 63.58, 14.66 (d, J = 51.0 Hz), 13.97 (d, J = 51.0 Hz);

[0314] 31 P NMR (162 MHz, DMSO-d6) δ (ppm): 37.67;

[0315] HRMS (ESI): calcd. for Chemical Formula: C 14 H 13 Cl3NO5P[M+H] + 411.96697, found: 411.96706.

[0316] Example 26

[0317] Preparation of compound 26

[0318] The preparation method of compound 26 was carried out according to the method of example 15, except that (1-hydroxyethyl)dimethylphosphine oxide was replaced by 1-[(2,4-dichlorophenyl)hydroxymethyl]dimethylphosphine oxide (its structural formula is shown as formula (18)) in equal amount.

[0319] The obtained pure product was white solid with a yield of 83.8% and a melting point (m.p.) of 125-126°C.

[0320] Structural identification data of compound 26 product: 1 H NMR (400 MHz, CDCl3) δ (ppm): 7.77 (d, J = 2.3 Hz, 1H, Ar-H), 7.53 (d, J = 8.1 Hz, 1H, Ar-H), 7.44 (s, 1H, Ar-H), 7.33 (d, J = 8.1 Hz, 1H, Ar-H), 6.53 (s, 1H, CH), 5.05 (dd, J = 63.9, 16.3 Hz, 2H, CH2), 1.66 (d, J = 11.8 Hz, 3H, CH3), 1.47 (d, J = 11.2 Hz, 3H, CH3);

[0321] 13 C NMR (101 MHz, CDCl3) δ (ppm): 167.16 (d, J = 6.4 Hz), 158.59, 156.16, 149.82, 133.79, 128.49, 128.43, 127.45, 127.31 (d, J = 2.3 Hz), 118.03 (d, J = 26.1 Hz), 115.00 (d, J = 8.8 Hz), 114.26 (d, J = 22.9 Hz), 70.89 (d, J = 83.7 Hz), 66.65, 13.86 (d, J = 34.3 Hz), 13.17 (d, J = 34.3 Hz);

[0322] 31 P NMR (162 MHz, CDCl3) δ (ppm): 41.66;

[0323] HRMS (ESI): calcd. for Chemical Formula: C 16 H 13 Cl5NO4P[M+H] + 489.90976, found: 489.91008.

[0324] Example 27

[0325] Preparation of compound 27

[0326] The preparation method of compound 27 was carried out according to the method of example 15, except that (1-hydroxyethyl)dimethylphosphine oxide was replaced by 1-[(3,4-dichlorophenyl)hydroxymethyl]dimethylphosphine oxide (its structural formula is shown as formula (19)) in equal amount.

[0327] The obtained pure product was white solid with a yield of 84.5% and a melting point (m.p.) of 143-144℃.

[0328] Structural identification data of compound 27 product: 1 H NMR (400 MHz, CDCl3) δ (ppm): 7.81 (d, J = 3.7 Hz, 1H, Ar-H), 7.46 (d, J = 12.4 Hz, 2H, Ar-H), 7.27 (s, 1H, Ar-H), 6.10 (s, 1H, CH), 5.08 (dd, J = 41.5, 14.5 Hz, 2H, CH2), 1.55 (d, J = 12.5 Hz, 3H, CH3), 1.43 (d, J = 10.4 Hz, 3H, CH3).

[0329] 13 C NMR (101 MHz, CDCl3) δ (ppm): 166.55, 155.28, 143.24, 140.89, 133.35 (d, J = 23.1 Hz), 132.46, 130.89, 128.70, 126.44, 123.57, 117.23, 73.54, 72.76, 63.63, 14.31 (d, J = 69.5 Hz), 12.73 (d, J = 68.8 Hz).

[0330] 31 P NMR (162 MHz, CDCl3) δ (ppm): 42.76.

[0331] HRMS (ESI): calcd. for Chemical Formula: C 16 H 13 Cl5NO4P [M+H]+489.90976, found: 489.90951.

[0332] Example 28

[0333] Preparation of compound 28

[0334] The preparation method of compound 28 was carried out according to the method of example 15, except that (1-hydroxyethyl)dimethylphosphine oxide was replaced by 1-[(4-methylphenyl)hydroxymethyl]dimethylphosphine oxide (its structural formula is shown as formula (20)) in equal amount.

[0335] The obtained pure product was white solid with a yield of 84.5% and a melting point (m.p.) of 143-144°C.

[0336] Structure identification data of compound 28 product: 1 H NMR (400 MHz, CDCl3) δ (ppm): 7.76 (d, J = 22.2 Hz, 1H, Ar-H), 7.22 (dd, J = 28.9, 7.7 Hz, 4H, Ar-H), 6.10 (s, 1H, CH), 5.07 (dd, J = 53.0, 16.1 Hz, 2H, CH2), 2.32 (d, J = 21.8 Hz, 3H, CH3), 1.47 (dd, J = 27.9, 12.7 Hz, 2x3H, CH3);

[0337] 13 C NMR (101 MHz, CDCl3) δ (ppm): 166.70 (d, J = 6.6 Hz), 155.41, 143.24, 140.72, 139.01, 129.59, 129.24, 127.03 (d, J = 4.1 Hz), 123.30, 117.21, 74.64 (d, J = 81.0 Hz), 63.71, 21.25, 14.05 (d, J = 69.0 Hz), 12.96 (d, J = 69.0 Hz);

[0338] 31 P NMR (162 MHz, CDCl3) δ (ppm): 42.50;

[0339] HRMS (ESI): calcd. for Chemical Formula: C 17 H 17 Cl3NO4P [M+H]+436.00335, found: 436.00249.

[0340] Test Example 3

[0341] Primary screening test of weed inhibition activity of compounds 15 to 28.

[0342] Test materials: barnyard grass, crabgrass, dogtail grass, abutilon, amaranthus retroflexus, earthnut pea, sowthistle, spiny amaranth, gooseweed, hollowhead amaranth.

[0343] Control: 95%;

[0344] Herbicidal activity primary screening test method:

[0345] Activity general screening (pot method, post-emergence stem-leaf spray treatment): The test targets were barnyardgrass, crabgrass, dogtailgrass, abutilon, amaranthus retroflexus, eclipta, goosefoot, spiny amaranth, gooseweed, and hollowhead amaranth. Inner diameter 7.5 cm pots were filled with compound nutrient soil to ¾, and the six kinds of weeds above were directly seeded (germination rate ≥ 85%) and covered with 0.2 cm of soil. After the soil was saturated with water at the bottom, the pots were placed in a greenhouse for growth. The soil moisture content was maintained as appropriate, and the weeds were grown until they reached the 3-leaf stage for use. Each compound was applied at a dose of 450, 150 g a.i. / ha using an automatic spray tower (model: 3WPSH-700E), and after the weed leaves were dried, the pots were moved to the greenhouse for cultivation. The activity (%) against weeds was investigated 20 days and 35 days later, and the results were expressed as growth inhibition rate (%). The results are shown in Tables 6 and 7.

[0346] Activity general screening (pot method, pre-emergence soil sealing treatment): The test targets were barnyardgrass, crabgrass, dogtailgrass, abutilon, amaranthus retroflexus, eclipta, goosefoot, spiny amaranth, gooseweed, and hollowhead amaranth. Inner diameter 7.5 cm pots were filled with compound nutrient soil to ¾, and the seeds were sown (germination rate ≥ 85%) and covered with soil the day before spraying. After the soil was saturated with water at the bottom, the pots were placed in a greenhouse for growth. The soil moisture content was maintained as appropriate, and the weeds were grown until they reached the 3-leaf stage for use. Each compound was applied at a dose of 450, 150 g a.i. / ha using an automatic spray tower (model: 3WPSH-700E), and after the pots were naturally dried in a ventilation hall for 2-3 hours, they were moved to the greenhouse for cultivation. The activity (%) against weeds was investigated 20 days and 35 days later, and the results were expressed as growth inhibition rate (%). The results are shown in Tables 8 and 9.

[0347] Table 6: Herbicidal activity screening results of test compounds (growth inhibition rate, %) - post-emergence stem-leaf spray treatment (20 days, 35 days after application)

[0348] Table 7: Herbicidal activity screening results of test compounds (growth inhibition rate, %) - post-emergence stem-leaf spray treatment (20 days, 35 days after application)

[0349] As can be seen from the data in Table 6 and Table 7, after the post-emergence stem-leaf spray treatment at the dosage of 450 and 150 g a.i. / ha, it was found that the compounds 15 to 28 according to the present application all have certain herbicidal activity, and the overall inhibition activity on broadleaf weeds is significantly better than that on grass weeds, wherein the activity of compound 17 is the highest, at the dosage of 450 g a.i. / ha, it was found that after 35 days of treatment, it has high activity on 10 kinds of tested targets (3 kinds of grass weeds and 7 kinds of broadleaf weeds), and the activity is all above 90%, the activities of compounds 15, 16, 20, 21, 22, 18 and 19 are the second, and at the dosage of 450 g a.i. / ha, they all have high activity on 7-9 kinds of tested targets, and the activity is all above 80%. It was also found that even when the concentration of the compound according to the present application is reduced to 150 g a.i. / ha, compound 17 still shows 60-100% inhibition activity on 10 kinds of tested targets after 35 days of treatment. Compared with clacyfos, the inhibition activity of compound 17 on both grass weeds and broadleaf weeds is more excellent.

[0350] Table 8: Herbicidal activity screening results (growth inhibition rate, %) of tested compounds - pre-emergence soil sealing treatment (after 20 days, 35 days of treatment)

[0351] Table 9: Herbicidal activity screening results (growth inhibition rate, %) of tested compounds - pre-emergence soil sealing treatment (after 20 days, 35 days of treatment)

[0352] As can be seen from the data in Table 8 and Table 9, after the pre-emergence soil sealing treatment at the dosage of 450 and 150 g a.i. / ha, it was found that the compounds 15 to 28 according to the present application have significantly better overall sealing herbicidal activity on broadleaf weeds than on grass weeds, and the sealing activity of compound 17 on targets is the highest, at the dosage of 450 g a.i. / ha, it was found that after 35 days of treatment, compound 17 has high activity on 10 kinds of tested targets (3 kinds of grass weeds and 7 kinds of broadleaf weeds), and the activity is all above 80%, and the activities of compounds 15, 16, 25, 26, 27 and 28 are the second. And clacyfos has almost no inhibition activity on grass weeds in sealing treatment, which shows that the organic phosphine compounds according to the present application have excellent inhibition activity on weeds before and after emergence.

[0353] Test Example 4

[0354] Test of the herbicidal spectrum of compound 17

[0355] Test materials: Xanthium, Amaranthus retroflexus, Cassia, Brassica juncea, Abutilon theophrasti, Medicago polymorpha, Viola, Ipomoea, Aeschynomene, Veronica, Portulaca, Chenopodium, Rumex, Euphorbia, Galium aparine, Stellaria, Capsella, Lamium, Conyza, Galium aparine, Eleusine indica, Eragrostis curvula, Eragrostis pilosa, Digitaria sanguinalis, Eleusine indica, Eragrostis pilosa, etc.

[0356] Herbicidal activity primary screening test method: Take an inner diameter of 7.5 cm flowerpot, fill with compound nutrient soil to 3 / 4, directly sow crop seeds (germination rate ≥ 85%), cover with soil, and add water to keep the soil moist, and wait for the weeds to grow to 3-4 leaf stage for standby. Compound 17 is applied at a dose of 450 g a.i. / ha in an automatic spray tower, and then moved to a greenhouse for culture. After 35 days, the results are observed by visual inspection (growth inhibition rate, %), and the results are shown in Table 10.

[0357] Table 10 Test results of the herbicidal activity spectrum of high-activity compound 17 (growth inhibition rate, %) - post-emergence stem and leaf spraying treatment (35 days after treatment)

[0358] As can be seen from the data in Table 10, after post-emergence stem and leaf spraying at a treatment dose of 450 g a.i. / ha, the results observed 35 days after treatment are as follows: compound 17 has a super-high herbicidal spectrum activity against the 23 types of broadleaf weeds tested, and a relatively wide herbicidal spectrum. Except for slightly poor activity against Cassia, Viola, and Conyza, the inhibition rate against other broadleaf weeds tested is 100%. It has excellent inhibition activity against Digitaria sanguinalis, Eleusine indica, and Eragrostis pilosa in the grass family.

[0359] Test Example 5

[0360] Further test of the herbicidal spectrum of high-activity compound 17 at a reduced concentration

[0361] Test materials are shown in Table 11:

[0362] Table 11 List of test weeds

[0363] Control agents: 95% clacyfos and 95% glyphosate;

[0364] Test method: This test was carried out according to the method of "NY / T 1155.4-2006 Pesticide Indoor Biological Test Guidelines Herbicide Part 4: Activity Determination Test Stem and Leaf Spraying Method", and the results are shown in Table 12.

[0365] Table 12 Fresh weight inhibition rate of compound 17 against 19 weeds - 15 days after treatment

[0366] The data and test results in Table 12 show that the sensitive weeds treated with compound 17 have symptoms of stem base hyperplasia and deformity; 15 days after treatment, 5 kinds of broadleaf weeds, including small plantain, pigweed, alligator weed, morning glory, and field senna, are highly sensitive (the control effect is greater than 80%) at a dose of 37.5 g a.i. / ha of compound 17; 9 kinds of broadleaf weeds, including nightshade, alligator weed, abutilon, morning glory, earthnut weed, pigweed, small plantain, field senna, and ironweed, and 1 kind of gramineous weed, including Chinese alpine rush, are highly sensitive at a dose of 75 g a.i. / ha of compound 17; and 14 kinds of broadleaf weeds, including three-leaf mustard, shepherd's purse, sheep hoof, small plantain, nightshade, abutilon, cornflower, morning glory, earthnut weed, pigweed, alligator weed, field senna, mustard, and ironweed, and 2 kinds of gramineous weeds, including foxtail grass and Chinese alpine rush, are highly sensitive at a dose of 150 g a.i. / ha of compound 17.

[0367] At the same dose (150 g a.i. / ha), the inhibitory activity of compound 17 on 15 kinds of test weeds, including earthnut weed, pigweed, small plantain, alligator weed, senna, field senna, three-leaf mustard, shepherd's purse, mustard, sheep hoof, cornflower, abutilon, morning glory, nightshade, and Chinese alpine rush, is significantly better than that of glyphosate; at the same dose (75 g a.i. / ha), the inhibitory rate of compound 17 on ironweed is higher than that of glyphosate. The recommended dose of glyphosate is currently 450 g a.i. / ha, and it can be seen from the data in Table 12 that even if compound 17 is significantly lower than 450 g a.i. / ha (such as 150 g a.i. / ha), the inhibitory activity of compound 17 on 13 kinds of test weeds, including earthnut weed, pigweed, small plantain, alligator weed, field senna, mustard, cornflower, abutilon, morning glory, nightshade, ironweed, foxtail grass, and Chinese alpine rush, is still better than or equivalent to the control effect of glyphosate at a dose of 450 g a.i. / ha; at a dose of 75 g a.i. / ha, the inhibitory activity of compound 17 on 9 kinds of test weeds, including earthnut weed, pigweed, alligator weed, field senna, abutilon, morning glory, nightshade, ironweed, and Chinese alpine rush, is still better than or equivalent to the control effect of glyphosate at a dose of 450 g a.i. / ha. In addition, at the same dose (75 g a.i. / ha), the inhibitory activity of compound 17 on 15 of the 19 test weeds is significantly better than that of clacyfos.

[0368] Therefore, the organic phosphine compound described in the present application shows better herbicidal activity, in particular, compound 17, the overall herbicidal activity is higher than that of clacyfos, and the herbicidal spectrum becomes wider, the inhibitory activity on a variety of weeds is better than that of glyphosate, and has good application value.

[0369] The preferred embodiments of the present application are described in detail above, but the present application is not limited thereto. Within the technical concept of the present application, various simple modifications can be made to the technical solutions of the present application, including that each technical feature is combined in any other suitable manner. These simple modifications and combinations should also be considered as disclosed by the present application and fall within the protection scope of the present application.

Claims

1. An organophosphorus compound and its stereoisomers, geometric isomers, tautomers, racemates, nitrides, hydrates, solvates, and pharmaceutically acceptable salts, characterized in that, The organic phosphine compound has a structural formula as shown in formula (I): wherein R 1 and R 2 are each C1-C6 alkyl, C1-C6 alkoxy, or R 1 and R 2 are connected to P to form a six-membered ring; R 3 is hydrogen, methyl, ethyl, propyl, furanyl, thienyl, pyridyl, phenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, or 4-methylphenyl; R 4 , R 5 , and R 6 are each hydrogen, C1-C3 alkyl, or halogen; X is C or N; and Z is 2. The organic phosphine compound according to claim 1, and stereoisomers, geometric isomers, tautomers, racemates, nitroso compounds, hydrates, solvates, and pharmaceutically acceptable salts thereof, characterized in that, The structural formula of the organic phosphine compound is shown as formula (I-1) or (I-2): wherein, two R are each methyl or ethyl; R3 is hydrogen, methyl, ethyl, furanyl, thienyl or pyridyl; and R4 is hydrogen or chlorine.

3. The organophosphorus compound and its stereoisomers, geometric isomers, tautomers, racemates, nitrides, hydrates, solvates, and pharmaceutically acceptable salts according to claim 2, characterized in that, The organic phosphine compound is selected from the following compounds:

4. The organic phosphine compound according to claim 1, and stereoisomers, geometric isomers, tautomers, racemates, nitroso compounds, hydrates, solvates, and pharmaceutically acceptable salts thereof, characterized in that, The structural formula of the organic phosphine compound is shown as formula (I-3): wherein R 3 is methyl, ethyl, propyl, 4-chlorophenyl, phenyl, thienyl, furanyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, or 4-methylphenyl; R 4 , R 5 and R 6 are each hydrogen, methyl, or halogen; and X is C or N.

5. The organic phosphine compound according to claim 4, characterized in that, 5 The organic phosphine compound is selected from the following compounds:

6. A method for producing the organic phosphine compound according to any one of claims 1 to 5, characterized by, The method comprises: reacting a compound shown in formula (II) with a compound shown in formula (III), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , X and Z are as defined in claim 1 and L is hydrogen or halogen.

7. The method of claim 6, wherein, The structural formula of the compound represented by formula (II) is formula (II-1), and the structural formula of the compound represented by formula (III) is formula (III-1), wherein, two R are each methyl or ethyl; R3 is hydrogen, methyl, ethyl, furanyl, thienyl or pyridyl; and R4 is hydrogen or chlorine. The process of the reaction comprises the following steps: S1, mixing a compound shown in formula (II), a first acid-binding agent and a first solvent; S2, under stirring, dropping a compound shown in formula (III) into the mixture obtained in step S1, and then reacting.

8. The method of claim 7, wherein, The first acid-binding agent is pyridine and / or triethylamine. Preferably, the first solvent is dichloromethane and / or tetrahydrofuran. Preferably, the molar ratio of the compound shown in formula (II-1), the compound shown in formula (III-1) and the first acid-binding agent is 1:(1-4):(1-5). Preferably, the temperature during stirring is -10-10℃. Preferably, the reaction condition comprises a temperature of 10-50℃ and a time of 0.5-5h.

9. The method of claim 6, wherein, The structural formula of the compound represented by formula (II) is formula (II-2), and the structural formula of the compound represented by formula (III) is formula (III-1), wherein R 3 is hydrogen, methyl, ethyl, furanyl, thienyl or pyridyl; R 4 is hydrogen or chloro; The process of the reaction comprises the following steps: S3, mixing a compound shown in formula (II-2), a second acid-binding agent and a second solvent; S4, under stirring, dropping a compound shown in formula (III-1) into the mixture obtained in step S3, and then reacting.

10. The method of claim 9, wherein, The molar ratio of the compound shown in formula (II-2), the compound shown in formula (III-1) and the second acid-binding agent is 1:(1-4):(1-5). Preferably, the temperature during stirring is -10-10℃. Preferably, the reaction condition comprises a temperature of 10-50℃ and a time of 0.5-5h. Preferably, the second acid-binding agent is pyridine and / or triethylamine. Preferably, the second solvent is dichloromethane and / or tetrahydrofuran.

11. The method of claim 6, wherein, The structural formula of the compound represented by formula (II) is formula (II-3), and the structural formula of the compound represented by formula (III) is formula (III-2), wherein R 3 is methyl, ethyl, propyl, 4-chlorophenyl, phenyl, thienyl, furanyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, or 4-methylphenyl; R 4 , R 5 and R 6 are each hydrogen, methyl, or halogen; and X is C or N. The process of the reaction comprises the following steps: S5, mixing a compound shown in formula (III-2), a third solvent and a condensing agent for reaction; S6, mixing a compound shown in formula (II-3), a catalyst and the material obtained in step S5 for reaction.

12. The method of claim 11, wherein, The third solvent is selected from one or more than two of acetonitrile, dichloromethane and tetrahydrofuran; Preferably, the condensing agent is selected from one or more than two of dicyclohexyl carbodiimide, 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide and carbonyl diimidazole; The catalyst is 4-N,N-dimethylpyridine and / or 1-hydroxybenzotriazole.

13. The method according to claim 11 or 12, characterized in that, The molar ratio of the compound shown in formula (II-3), the compound shown in formula (III-2), the condensing agent and the catalyst is 1:(1-1.2):(1-1.2):(0.05-0.1).

14. The method according to any one of claims 11-13, characterized in that, The reaction condition in step (1) comprises a temperature of 10-40℃ and a time of 5-30min. Preferably, the reaction condition in step (2) comprises a temperature of 20-80℃ and a time of 3-10h.

15. A pharmaceutical composition comprising, The pharmaceutical composition contains the organic phosphine compound or its stereoisomer, geometric isomer, tautomer, racemate, nitroxide, hydrate, solvate and pharmaceutically acceptable salt according to any one of claims 1 to 5.

16. Use of the organic phosphine compound according to any one of claims 1 to 5, and its stereoisomer, geometric isomer, tautomer, racemate, nitroxide, hydrate, solvate and pharmaceutically acceptable salt, or the pharmaceutical composition according to claim 15, for preventing and treating the growth of weeds.

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