Arylamino-containing xanthine derivative as well as preparation method and application thereof

Abstract

The invention relates to an arylamino-containing xanthine derivative as well as a preparation method and application thereof. On the basis of a 1, 3-disubstituted xanthine raw material, the xanthine derivative containing the arylamino group, which is obtained through a series of reactions, is shown as a general formula I in the specification. The compound of the general formula I has high herbicidal activity, and has obvious activity on rape, amaranthus retroflexus, barnyard grass and digitaria sanguinalis. The compound has good insecticidal activity, and especially has a remarkable effect on plutella xylostella. The compound has good bactericidal activity, and has obvious in-vitro inhibitory activity on fusarium graminearum, phytophthora capsici, sclerotinia sclerotiorum, fusarium wilt of cucumber, physalospora piricola, rhizoctonia cerealis and the like. The compound as shown in the general formula I can be used as an active component of a weeding or insecticidal or bactericidal composition, is used for preparing an agricultural herbicide or insecticide or bactericide, and can be used for preventing and treating weeds, pests or germs on various crops. The compound also has a good inhibition effect on the activity of KARI, and can be used as a KARI inhibitor. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of agricultural herbicides, insecticides and fungicides, relates to the synthesis and application of a KARI inhibitor, and specifically relates to a xanthine derivative containing an aromatic amino group and a preparation method and application thereof. Background Art

[0002] The prevention and control of weeds, plant pathogens and pests is of great significance to the smooth development of agriculture, forestry, animal husbandry, sideline production, fishery and public health, and pesticides play a vital role in this. In order to increase crop yields and overcome the defects of traditional pesticides in application, it is a long-term and arduous task to find highly active pesticides with novel structures and excellent performance.

[0003] Structural modification and optimization of biologically active natural products is one of the practical ways to design and discover new agrochemicals. Generally speaking, compounds designed in this way are more likely to have high biological activity and good biocompatibility. Xanthine natural alkaloids represented by theophylline (1,3-dimethylxanthine), caffeine and theobromine are widely present in a variety of plants and have been found to have potential insecticidal and antibacterial activities. This type of compound is closely related to people's diet and life, and often has low toxicity; research on this type of compound is mainly concentrated in the field of medicine. Various natural and synthetic xanthines and their derivatives can be used to treat neurodegenerative diseases, respiratory diseases, kidney diseases, cancer and cardiovascular diseases. However, the research and application of this type of compound in the field of pesticides are relatively small and need to be widely explored. Therefore, the research on structural modification and transformation of xanthine natural alkaloids to obtain new and environmentally friendly and efficient pesticide molecules has certain development space and application prospects. In addition, ketol-acid reductoisomerase (KARI) is one of the key enzymes in the biosynthesis of branched-chain amino acids and exists only in plants and microorganisms. Herbicides and fungicides designed with KARI as a pesticide target theoretically have the advantage of being safe for humans and mammals, which is in line with the research direction of green pesticides. Synthesizing and screening new compounds that inhibit KARI activity are of great significance in the research and development of new pesticides. In the prior art, the preparation method of a xanthine derivative containing an aromatic amino group and its application as an agricultural herbicide, insecticide, fungicide and KARI inhibitor reported in the present invention have not been disclosed. Summary of the invention

[0004] The object of the present invention is to provide a novel structure of a xanthine derivative containing an aromatic amino group as a substitute for a traditional agricultural herbicide, insecticide or fungicide, and a preparation method and use thereof. Such derivatives have good herbicidal activity, insecticidal activity and fungicidal activity, and can be applied to the integrated prevention and control of diseases, insects and weeds on various crops. At the same time, such derivatives also have good KARI inhibitory activity. Therefore, the present invention also includes the use of such derivatives as KARI inhibitors.

[0005] The present invention provides a xanthine derivative containing an aromatic amino group, which has a structural formula as shown in general formula I:

[0006]

[0007] Where:

[0008] R 1 , R 2 It is C 1 -C 6 Alkyl or halogenated C 1 -C 6 alkyl;

[0009] R 3 H or with R 4 The acyl group (R 4 C(=O)-), R 4 It is C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, aryl or aryl-substituted C 1 -C 3 Alkyl, in which the hydrogen on the aromatic ring can be further replaced by the following groups: halogen, C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, cyano, nitro, phenyl, C 1 -C 6 Alkoxy, halogenated C 1 -C 6 Alkoxy, C 1 -C 6 Alkylthio, halo 1 -C 6 Alkylthio, C 2 -C 6 Alkenyl, halogenated C 2 -C 6 Alkenyl, C 3 -C 6 Alkynyl, halo C 3 -C 6 Alkynyl, C 2 -C 6Alkenyloxy, halogenated C 2 -C 6 Alkenyloxy, C 3 -C 6 Alkynyloxy, halo C 3 -C 6 Alkynyloxy, phenoxy, pyridyloxy;

[0010] Ar is an aryl group, wherein the hydrogen atoms on the aryl ring may be further replaced by halogen, C 1 -C 6 Alkyl, halogenated C 1 -C 6 Alkyl, cyano, nitro, phenyl, C 1 -C 6 Alkoxy, halogenated C 1 -C 6 Alkoxy, C 1 -C 6 Alkylthio, halo 1 -C 6 Alkylthio, C 2 -C 6 Alkenyl, halogenated C 2 -C 6 Alkenyl, C 3 -C 6 Alkynyl, halo C 3 -C 6 Alkynyl, C 2 -C 6 Alkenyloxy, halogenated C 2 -C 6 Alkenyloxy, C 3 -C 6 Alkynyloxy, halo C 3 -C 6 Alkynyloxy, phenoxy, pyridyloxy;

[0011] In the above definition of derivatives, the terms used, whether used alone or in compound words, are generally defined as follows:

[0012] Halogen is fluorine, chlorine, bromine or iodine;

[0013] The alkyl group is a straight chain, branched chain alkyl group or a cycloalkyl group, wherein the cycloalkyl group includes a cyclic chain form or an alkyl form with a cyclic chain, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl and the like groups;

[0014] Aryl is phenyl or an aromatic heterocyclic group, for example, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl;

[0015] The alkenyl group is a straight or branched group having 2 to 6 carbon atoms and may have a double bond at any position, for example, a group such as vinyl, propenyl, allyl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1-yl, 2-methylbut-2-en-1-yl, 3-methylbut-2-en-1-yl, pent-2-en-1-yl, pent-3-en-1-yl, pent-4-en-1-yl, 2-methylpent-2-en-1-yl, 3-methylpent-2-en-1-yl, hex-2-en-1-yl, hex-3-en-1-yl, hex-4-en-1-yl or hex-5-en-1-yl;

[0016] Alkynyl is a straight or branched chain having 3 to 6 carbon atoms and may have a triple bond at any position, for example, propynyl, propargyl, but-2-yn-1-yl, but-3-yn-1-yl, pent-2-yn-1-yl, pent-3-yn-1-yl, pent-4-yn-1-yl, 4-methylpent-2-yn-1-yl, hex-2-yn-1-yl, hex-3-yn-1-yl, hex-4-yn-1-yl or hex-5-yn-1-yl;

[0017] The carbon skeleton of the alkoxy group is the same as that of the alkyl group defined therein, and in this context, the alkoxy group refers to a group with an oxygen atom attached to the end of the alkyl group, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentyloxy, n-hexyloxy, cyclopropyloxy, cyclopropylmethoxy, cyclobutyloxy, cyclobutylmethoxy, cyclopentyloxy, cyclopentylmethoxy or cyclohexyloxy groups;

[0018] The carbon skeleton of the alkylthio group is the same as that of the alkyl group defined therein, and in this context, the alkylthio group refers to a group having a sulfur atom attached to the end of the alkyl group, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, n-pentylthio, isopentylthio, n-hexylthio, cyclopropylthio, cyclopropylmethylthio, cyclobutylthio, cyclobutylmethylthio, cyclopentylthio, cyclopentylmethylthio or cyclohexylthio;

[0019] The carbon skeleton of alkenyloxy is the same as that of alkenyl, which is defined as above. In this context, alkenyloxy refers to a group with an oxygen atom attached to the end of the alkenyl, such as vinyloxy, allyloxy, etc.

[0020] The carbon skeleton of the alkynyloxy group is the same as that of the alkynyl group defined therein. The definition of the alkynyl group is as described above. In this context, the alkynyloxy group refers to a group with an oxygen atom attached to the end of the alkynyl group, such as propargyloxy.

[0021] Haloalkyl is a straight chain alkyl, branched chain alkyl or cycloalkyl group, and the hydrogen atoms on these alkyl groups may be partially or completely substituted by halogen atoms; "haloalkoxy", "haloalkylthio", "haloalkenyl", "haloalkynyl", "haloalkenyloxy" and "haloalkynyloxy" are defined similarly to the term "haloalkyl";

[0022] When it is said that it may be further substituted, the number of the substituents may be one or more.

[0023] The preparation method of the compound of general formula I of the present invention is characterized in that the reaction route of the preparation method is shown in the following formula:

[0024]

[0025] Where R 1 , R 2 , R 3 , R 4 , Ar are as defined above unless otherwise specified;

[0026] The preparation method is:

[0027] 1) In an organic solvent, the compound of formula A is reacted with an arylamine and polyformaldehyde ((CH 2 O) n ) at the boiling point of the solvent for 15-30 hours to obtain a compound of formula I, wherein R 3 =H; the molar ratio of the compound of formula A, the arylamine and the paraformaldehyde is 1:1.2:2; the organic solvent is methanol, ethanol, propanol, isopropanol or tert-butanol;

[0028] 2) Under argon protection, the R 3 =H, and 1.1 equivalents of R 4 The acyl chloride and 3.0 equivalents of base are reacted in an organic solvent at 0°C for 2-4 hours to obtain R 3 =R 4 The compound of formula I of CO, wherein the substituents are as defined above unless otherwise specified; the base is sodium hydroxide, potassium hydroxide, potassium carbonate, cesium carbonate, potassium tert-butoxide, triethylamine or diisopropylethylamine; the organic solvent is dichloromethane, tetrahydrofuran or 1,4-dioxane.

[0029] The compound of the general formula I of the present invention has high herbicidal activity, and has obvious effects on dicotyledonous plants such as rape and Amaranthus retroflexus, and monocotyledonous plants such as barnyard grass and crabgrass. The compound of the general formula I of the present invention has good insecticidal activity against Plutella xylostella and the like. The compound of the general formula I of the present invention has good in vitro inhibitory activity against wheat fusarium, pepper phytophthora, rapeseed sclerotinia, cucumber wilt, apple ring rot and wheat sheath blight. At the same time, the compound of the general formula I also has good inhibitory activity against KARI. Therefore, the present invention also includes the use of the compound of the general formula I for controlling weeds, insect pests and pathogenic bacteria on various crops, and as a KARI inhibitor.

[0030] The present invention also includes a herbicidal, insecticidal or fungicidal composition with the compound of general formula I as an active ingredient, which can be used to prepare agricultural herbicides, insecticides or fungicides. The herbicidal, insecticidal or fungicidal composition also includes an agricultural, forestry or hygienic acceptable carrier.

[0031] Advantages and beneficial effects of the present invention:

[0032] The present invention provides a novel xanthine derivative containing aromatic amino groups (compound of general formula I), which has good herbicidal activity, insecticidal activity, fungicidal activity and KARI inhibitory activity. It has good control effect on weedy plants such as rape, Amaranthus retroflexus, barnyard grass, crabgrass, etc., pests such as diamondback moth, etc., and crop pathogens such as wheat fusarium, pepper phytophthora, rapeseed sclerotinia, cucumber wilt, apple ring rot, wheat sheath blight, etc., can be used as an active component of a weeding, insecticidal or fungicidal composition, used for preparing agricultural herbicides, insecticides or fungicides, and can be used for the prevention and control of weeds, insect pests or pathogenic bacteria; it also has a good inhibitory effect on the activity of KARI and can be used as an inhibitor of KARI. DETAILED DESCRIPTION

[0033] The present invention is further described below in conjunction with the examples, the purpose of which is to better understand the content of the present invention and reflect the essential characteristics of the present invention, so the examples cited should not be regarded as limiting the scope of protection of the present invention. It is also particularly pointed out here that the specific experimental methods and equipment involved in the examples are conventional methods or implemented under the conditions recommended by the manufacturer's instructions unless otherwise specified, and the reagents involved are commercially available unless otherwise specified.

[0034] Example 1

[0035] A method for preparing 1,3-dimethyl-7-((phenylamino)methyl)-3,7-dihydro-1H-purine-2,6-dione (Compound I-1).

[0036] The reaction route is shown below:

[0037]

[0038] The preparation method is as follows:

[0039] Theophylline A (10 mmol), aniline (12 mmol), paraformaldehyde (20 mmol) and anhydrous ethanol (20 mL) were placed in a 100 mL round-bottom flask and heated under reflux for 24 hours. The mixture was cooled naturally and filtered to obtain a filtrate. After desolventizing under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid, which was then filtered, washed and dried to obtain compound I-1 as a yellow solid with a yield of 42%.

[0040] Example 2

[0041] A method for preparing 1,3-dimethyl-7-((o-toluylamino)methyl)-3,7-dihydro-1H-purine-2,6-dione (Compound I-2).

[0042] The reaction route is shown below:

[0043]

[0044] The preparation method is as follows:

[0045] Theophylline A (10 mmol), o-toluidine (12 mmol), paraformaldehyde (20 mmol) and anhydrous ethanol (20 mL) were placed in a 100 mL round-bottom flask and heated under reflux for 20 hours. The mixture was cooled naturally and filtered to obtain a filtrate. After desolventizing under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid, which was then filtered, washed and dried to obtain compound I-2 as a yellow solid with a yield of 40%.

[0046] Example 3

[0047] A method for preparing 7-(((3,4-difluorophenyl)amino)methyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (Compound I-9).

[0048] The reaction route is shown below:

[0049]

[0050] The preparation method is as follows:

[0051] Theophylline A (10 mmol), 3,4-difluoroaniline (12 mmol), paraformaldehyde (20 mmol) and anhydrous ethanol (20 mL) were placed in a 100 mL round-bottom flask and heated under reflux for 20 hours. Natural cooling and suction filtration were performed to obtain a filtrate. After desolventizing under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid, which was then suction filtered, washed and dried to obtain compound I-9 as a yellow solid with a yield of 33%.

[0052] Example 4

[0053] A method for preparing 7-(((4-chloro-2-methoxyphenyl)amino)methyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (Compound I-13).

[0054] The reaction route is shown below:

[0055]

[0056] The preparation method is as follows:

[0057] Theophylline A (10 mmol), 4-chloro-2-methoxyaniline (12 mmol), paraformaldehyde (20 mmol) and anhydrous ethanol (20 mL) were placed in a 100 mL round-bottom flask and heated under reflux for 24 hours. Natural cooling and suction filtration were performed to obtain a filtrate. After desolventizing under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid, which was then suction filtered, washed and dried to obtain compound I-13 as a white solid with a yield of 41%.

[0058] Example 5

[0059] A method for preparing 1,3-dimethyl-7-((pyrimidin-2-ylamino)methyl)-3,7-dihydro-1H-purine-2,6-dione (Compound I-14).

[0060] The reaction route is shown below:

[0061]

[0062] The preparation method is as follows:

[0063] Theophylline A (10 mmol), pyrimidine-2-amine (12 mmol), paraformaldehyde (20 mmol) and anhydrous ethanol (20 mL) were placed in a 100 mL round-bottom flask and heated under reflux for 22 hours. Natural cooling was performed and suction filtration was performed to obtain a filtrate. After desolventizing under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid, which was then suction filtered, washed and dried to obtain compound I-14 as a white solid with a yield of 44%.

[0064] Example 6

[0065] A method for preparing 2-chloro-N-((1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)methyl)-N-(o-tolyl)acetamide (Compound I-18).

[0066]

[0067] Compound I-2 (1 mmol) prepared in Example 2, NaOH (3 mmol) and 5 mL of dichloromethane were added to a round-bottom flask, and chloroacetyl chloride (1.1 mmol) was added at 0°C in an argon atmosphere, and the reactants were magnetically stirred for 3 hours at 0°C. 10 mL of water was added to the reaction system for washing, and the organic phase was separated and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by column chromatography (dichloromethane / methanol, v / v=120:1) to obtain compound I-18 as a white solid with a yield of 37%.

[0068] Example 7

[0069] A method for preparing 2-chloro-N-(3,4-difluorophenyl)-N-((1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)methyl)acetamide (Compound I-22).

[0070]

[0071] Compound I-9 (1 mmol) prepared in Example 2, NaOH (3 mmol) and 5 mL of dichloromethane were added to a round-bottom flask, and chloroacetyl chloride (1.1 mmol) was added under an argon atmosphere at 0°C, and the reactants were magnetically stirred for 3 hours at 0°C. 10 mL of water was added to the reaction system for washing, and the organic phase was separated and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by column chromatography (dichloromethane / methanol, v / v=120:1) to obtain compound I-22 as a white solid with a yield of 35%.

[0072] Example 8

[0073] A method for preparing 2-chloro-N-(4-chloro-2-methoxyphenyl)-N-((1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)methyl)acetamide (Compound I-24).

[0074]

[0075] Compound I-13 (1 mmol) prepared in Example 2, NaOH (3 mmol) and 5 mL of dichloromethane were added to a round-bottom flask, and chloroacetyl chloride (1.1 mmol) was added at 0°C in an argon atmosphere, and the reactants were magnetically stirred for 3 hours at 0°C. 10 mL of water was added to the reaction system for washing, and the organic phase was separated and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain a crude product, which was purified by column chromatography (dichloromethane / methanol, v / v=120:1) to obtain compound I-24 as a white solid with a yield of 31%.

[0076] The following Table 1a and Table 1b list the structures and physical properties of some compounds of Formula I.

[0077] Table 1a Structures and physical properties of some compounds of formula I

[0078]

[0079]

[0080] Table 1b Structures and physical properties of some compounds of formula I

[0081]

[0082] Table 2 lists the NMR and HRMS data of some compounds of formula I.

[0083] Table 2 NMR and HRMS data of some compounds of general formula I

[0084]

[0085]

[0086]

[0087]

[0088]

[0089]

[0090] Examples of biological activity tests of compounds of formula I

[0091] Example 9

[0092] The herbicidal activity of the compound provided by the invention is measured.

[0093] (1) Plate method: Rapeseed (Brassica campestris) was used as the test object. A filter paper with a diameter of 5.6 cm was placed in a culture dish with a diameter of 6 cm. 2 mL of a test compound solution with a concentration of 100 μg / mL or 10 μg / mL (the compound was dissolved in DMF and then diluted to the required concentration with distilled water) was poured into the dish. Fifteen rapeseed seeds that had been soaked in distilled water for 4 hours were added thereto. The culture dish was then placed at 28±1°C. After 65 hours of dark culture, the radicle length was measured. The herbicidal activity of the compound was detected by the inhibition of the growth of the rapeseed radicle under dark conditions. The inhibition rate was compared with that of the blank control to obtain the corresponding inhibition rate.

[0094] (2) Small cup method: Echinochloa crus-galli was used as the test object. Glass beads and filter paper were placed in a 50-mL small beaker. 6 mL of a 100 μg / mL or 10 μg / mL solution of the test compound (the compound was dissolved in DMF and diluted to the required concentration with distilled water) was poured into the beaker. Ten newly white Echinochloa seeds were added. The beaker was then placed at 28±1°C. After 65 hours of light culture, the height of the seedlings was measured. The herbicidal activity of the compound was detected by the inhibition of the growth of the height of the Echinochloa seedlings under light conditions. The inhibition rate was compared with that of the blank control to obtain the corresponding inhibition rate.

[0095] The growth inhibition rates of some compounds of general formula I obtained by the above plate method and cup method on rapeseed and barnyard grass are shown in Table 3.

[0096] Table 3 Growth inhibition rate of some compounds of general formula I on rapeseed and barnyard grass

[0097]

[0098]

[0099] (3) Potted method: Rapeseed (Brassica campestris), Amaranthus retroflexus, Echinochloa crus-galli and Digitaria adscendens were used as test objects. A fixed amount of soil was placed in a paper cup with a diameter of 7.0 cm, and an appropriate amount of water was added. After sowing, a layer of soil of a fixed thickness was covered and the plants were moved to a greenhouse for cultivation. Before the seedlings emerged, they were covered with plastic sheets and a fixed amount of clean water was applied every day to maintain normal plant growth. The test was divided into soil treatment (carried out before the seedlings emerged, that is, the soil was sprayed with different corresponding doses of the agent and then sown) and stem and leaf treatment (carried out after the seedlings emerged, that is, the stems and leaves were sprayed with different corresponding doses of the agent when the seedlings were one peduncle). The experimental results were investigated 15 days after the treatment, and the fresh weight of the aboveground part was measured. The fresh weight inhibition rate was calculated by comparing with the untreated group to measure the herbicidal effect of the compound.

[0100] The herbicidal activity test results of some compounds of the general formula I obtained in the above pot plant test are shown in Table 4.

[0101] Table 4 Herbicidal activity of some compounds of formula I

[0102]

[0103]

[0104] Example 10

[0105] The insecticidal activity of the compound provided by the invention is measured.

[0106] Bioactivity assay on diamondback moth (Plutella xylostella Linnaeus): The diamondback moth insecticidal activity test adopts the leaf dipping method, the test compound is dissolved with 1mL DMF, then diluted with distilled water to prepare a solution of the corresponding test concentration, and then immersed in cabbage leaves (5×1cm), the remaining liquid is shaken off after 3-5s, and after drying, it is placed in a 10cm long test tube, and 10 2-instar diamondback moth larvae are inoculated. Each sample is made into three groups, and the room temperature is maintained at 25±1°C. The blank control is only fed with cabbage leaves immersed in the DMF diluted solution. The experimental results are recorded after 72 hours, and the death standard of the larvae is immobility to touch. The toxicity of the test compound to the diamondback moth larvae is evaluated with 0-100% (lethality), where 0% means no insecticidal effect and 100% means complete killing.

[0107] The above insecticidal activity test results are shown in Table 5.

[0108] Table 5 Insecticidal activity of some compounds of general formula I

[0109]

[0110]

[0111] Embodiment 11

[0112] The fungicidal activity test was carried out using the compound of general formula I provided by the present invention.

[0113] Determination of fungicidal activity by in vitro plate method: The test objects were wheat fusarium, pepper phytophthora, rapeseed sclerotinia, cucumber wilt, apple ring rot and wheat sheath blight. The test compound was dissolved in DMSO to a concentration of 1.0×10 4 1.0mL of the test solution was added to 9mL of PDA medium under sterile conditions, and the test strain was inoculated. The culture medium with 1mL of sterile water was used as a blank control. After the culture medium was cultured in a constant temperature incubator at 25±1℃ for 72h, the colony diameter was measured and compared with the colony diameter in the blank test to calculate the inhibition rate.

[0114] The fungicidal activity test results of some compounds of general formula I at a concentration of 50 mg / L are shown below.

[0115] Inhibition rate of wheat fusarium rust: I-10 55.6%, I-15 36.1%, I-19 35.0%;

[0116] Inhibition rate of pepper phytophthora: I-6 36.1%, I-10 88.9%, I-17 41.7%, I-18 33.3%, I-19 33.3%;

[0117] Inhibition rate of Sclerotinia sclerotiorum in rapeseed: I-3 34.4%, I-6 93.8%, I-10 62.5%, I-10 98.4%, I-11 93.8%, I-12 81.3%, I-14 59.4%, I-15 50.0%, I-16 59.4%, I-17 31.3%, I-1964.2%, I-24 32.1%;

[0118] Inhibition rate of cucumber wilt pathogen: I-4 26.5%, I-11 30.6%, I-15 30.6%, I-18 22.4%, I-21 28.6%;

[0119] Inhibition rate of apple ring spot pathogen: I-2 30.9%, I-8 39.7%, I-10 39.7%, I-12 66.2%, I-13 30.3%, I-14 50.0%, I-15 73.5%, I-16 47.1%, I-17 39.7%, I-19 54.5%, I-2056.1%, I-24 51.5%;

[0120] The inhibition rate against wheat stripe rust: I-6 68.3%, I-11 39.0%, I-12 78.0%, I-21 39.5%, I-23 48.1%.

[0121] Example 12

[0122] The KARI inhibitory activity test was performed using the compound of general formula I provided by the present invention.

[0123] Test method: KARI was expressed in large quantities in E. coli cells transformed with a recombinant plasmid (containing the rice KARI gene), and the interaction between the compound and KARI was studied in vitro. The dynamic analysis method was used to add appropriate amounts of inhibitor solution, 0.1 mol / L Tris-HCl buffer (pH = 8.0), 0.2 mmol / L NADPH, 1 mmol / L MgCl 2 and an appropriate amount of rice KARI protein were mixed in a cuvette and kept at 30°C for 10 minutes. A mixture containing 0.1 mmol / L acetolactate was added to start the enzyme reaction. The slope of the initial linear change part (ΔOD 340The initial enzyme activity was represented by 1:100 nm / min, and the absorbance at 340 nm was continuously recorded (to monitor the reduction of NADPH). The activity inhibition curve of the inhibitor on the KARI enzyme was obtained, and the inhibition rate was calculated compared with the blank control. The results are shown in Table 6.

[0124] Table 6 Inhibitory activity of some compounds of general formula I against KARI at a concentration of 200 mg / L

[0125] No. Inhibition rate % No. Inhibition rate % No. Inhibition rate % I-1 58.3 I-9 37.5 I-17 30.0 I-2 72.2 I-10 56.9 I-18 30.0 I-3 59.7 I-11 0 I-19 57.0 I-4 27.8 I-12 27.8 I-20 37.0 I-5 37.5 I-13 79.0 I-21 74.0 I-6 62.9 I-14 34.7 I-22 66.0 I-7 76.4 I-15 19.4 I-23 52.0 I-8 15.3 I-16 28.9 I-24 61.0

Claims

1. A xanthine derivative containing an aromatic amino group, characterized in that It has the structural formula shown in general formula I: Where: R 1 , R 2 is C1-C6 alkyl or halogenated C1-C6 alkyl; R 3 H or with R 4 The acyl group (R 4 C(=O)-), R 4 It is C1-C6 alkyl, halogenated C1-C6 alkyl, aryl or aryl-substituted C1-C3 alkyl, wherein the hydrogen on the aryl ring may be further substituted by halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, cyano, nitro, phenyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C1-C6 alkylthio, halogenated C1-C6 alkylthio, C2-C6 alkenyl, halogenated C2-C6 alkenyl, C3-C6 alkynyl, halogenated C3-C6 alkynyl, C2-C6 alkenyloxy, halogenated C2-C6 alkenyloxy, C3-C6 alkynyloxy, halogenated C3-C6 alkynyloxy, phenoxy, pyridyloxy; Ar is an aromatic group, wherein the hydrogen on the aromatic ring may be further substituted by halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, cyano, nitro, phenyl, C1-C6 alkoxy, halogenated C1-C6 alkoxy, C1-C6 alkylthio, halogenated C1-C6 alkylthio, C2-C6 alkenyl, halogenated C2-C6 alkenyl, C3-C6 alkynyl, halogenated C3-C6 alkynyl, C2-C6 alkenyloxy, halogenated C2-C6 alkenyloxy, C3-C6 alkynyloxy, halogenated C3-C6 alkynyloxy, phenoxy, pyridyloxy.

2. The xanthine derivative containing an aromatic amino group according to claim 1, characterized in that: In the definition of derivatives, the terms used, whether used alone or in compound words, are generally defined as follows: The halogen is fluorine, chlorine, bromine or iodine; The alkyl group is specifically methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl or cyclohexyl; The aryl group is specifically phenyl, furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl; The alkenyl group is specifically vinyl, propenyl, allyl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1-yl, 2-methylbut-2-en-1-yl, 3-methylbut-2-en-1-yl, pent-2-en-1-yl, pent-3-en-1-yl, pent-4-en-1-yl, 2-methylpent-2-en-1-yl, 3-methylpent-2-en-1-yl, hex-2-en-1-yl, hex-3-en-1-yl, hex-4-en-1-yl or hex-5-en-1-yl; The alkynyl group is specifically propynyl, propargyl, but-2-yn-1-yl, but-3-yn-1-yl, pent-2-yn-1-yl, pent-3-yn-1-yl, pent-4-yn-1-yl, 4-methylpent-2-yn-1-yl, hex-2-yn-1-yl, hex-3-yn-1-yl, hex-4-yn-1-yl or hex-5-yn-1-yl; The alkoxy group is specifically methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentyloxy, n-hexyloxy, cyclopropyloxy, cyclopropylmethoxy, cyclobutyloxy, cyclobutylmethoxy, cyclopentyloxy, cyclopentylmethoxy or cyclohexyloxy; The alkylthio group is specifically methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, n-pentylthio, isopentylthio, n-hexylthio, cyclopropylthio, cyclopropylmethylthio, cyclobutylthio, cyclobutylmethylthio, cyclopentylthio, cyclopentylmethylthio or cyclohexylthio; The carbon skeleton of the alkenyloxy group is the same as that of the alkenyl group defined therein. The definition of the alkenyl group is as described above. Under this premise, the alkenyloxy group refers to a group with an oxygen atom attached to the end of the alkenyl group. The carbon skeleton of the alkynyloxy group is the same as that of the alkynyl group defined therein. The definition of the alkynyl group is as described above. Under this premise, the alkynyloxy group refers to a group with an oxygen atom attached to the end of the alkynyl group; The halogenated C1-C6 alkyl group is a straight-chain alkyl group, a branched alkyl group or a cycloalkyl group, and the hydrogen atoms on these alkyl groups may be partially or completely substituted by halogen atoms; the definitions of "halogenated C1-C6 alkoxy", "halogenated C1-C6 alkylthio", "halogenated C2-C6 alkenyl", "halogenated C3-C6 alkynyl", "halogenated C2-C6 alkenyloxy" and "halogenated C3-C6 alkynyloxy" are similar to the term "halogenated C1-C6 alkyl"; When it is said that it may be further substituted, the number of the substituents may be one or more.

3. A xanthine derivative containing an aromatic amino group according to claim 2, characterized in that: R 1 , R 2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclopropylmethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3-fluoropropyl, 3,3-difluoropropyl or 3,3,3-trifluoropropyl; R 3 H or with R 4 The acyl group (R 4 C(=O)-), R 4 It is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclopropylmethyl, halomethyl, haloethyl, halo-n-propyl, haloisopropyl, halo-n-butyl, haloisobutyl, halo-sec-butyl, halo-tert-butyl, halo-n-pentyl, haloisopentyl, halo-n-hexyl, haloisohexyl, halocyclopropyl, halocyclobutyl, halocyclopentyl, halocyclohexyl, halocyclopropylmethyl, aryl, arylmethyl, 1-arylethyl, 2-arylethyl, 1-arylpropyl, 2-arylpropyl, 3-arylpropyl, 1-aryl-1-methylethyl or 2-aryl-1-methylethyl, wherein the halo means that the hydrogen atoms on the carbon skeleton are replaced by a single or multiple halogen atoms; The aryl group is phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl, and the hydrogen on the aryl ring can be further substituted by the following groups: halogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, Cyclopropylmethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, cyano, nitro, phenyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylthio, ethylthio, trifluoromethylthio, trifluoroethylthio, vinyl, propenyl, allyl, propargyl, allyloxy, 3,3-dichloroallyloxy, propargyloxy, phenoxy or pyridyloxy; which may be further substituted, and the number of substituents may be one or more; Ar is an aryl group, wherein the aryl group is phenyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or triazinyl, and the hydrogen on the aryl ring may be further substituted by the following groups: halogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl, cyclobutyl, cyclopentyl ... hexyl, cyclopropylmethyl, trifluoromethyl, 2,2,2-trifluoroethyl, heptafluoroisopropyl, cyano, nitro, phenyl, methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylthio, ethylthio, trifluoromethylthio, trifluoroethylthio, vinyl, propenyl, allyl, propargyl, allyloxy, 3,3-dichloroallyloxy, propargyloxy, phenoxy or pyridyloxy; which may be further substituted, and the number of substituents may be one or more.

4. A xanthine derivative containing an aromatic amino group according to claim 3, characterized in that: R 1 , R 2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl or isohexyl; R 3 H or with R 4 The acyl group (R 4 C(=O)-), R 4 is halogenated methyl, halogenated ethyl, halogenated n-propyl, halogenated isopropyl, halogenated n-butyl, halogenated isobutyl, halogenated sec-butyl, halogenated tert-butyl, halogenated n-pentyl, halogenated isopentyl, halogenated n-hexyl or halogenated isohexyl, wherein the halogenated group refers to the hydrogen atoms on the carbon skeleton being replaced by a single or multiple halogen atoms; Ar is an aromatic group, which is phenyl, pyridyl or pyrimidinyl, and the hydrogen on the aromatic ring may be further substituted by halogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, methoxy, ethoxy, n-propoxy or isopropoxy; the group may be further substituted, and the number of substituents may be one or more.

5. A xanthine derivative containing an aromatic amino group according to claim 4, characterized in that: R 1 , R 2 It is methyl; R 3 H or with R 4 The acyl group (R 4 C(=O)-), R 4 It is monochloromethyl; Ar is phenyl, 2-methylphenyl, 4-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 4-chloro-2-methoxyphenyl, pyrimidin-2-yl, 4,6-dimethylpyrimidin-2-yl, 2-chloropyridin-3-yl.

6. The method for preparing the xanthine derivative containing an aromatic amino group according to claim 1, characterized in that Prepared by the following method: Where R 1 , R 2 , R 3 , R 4 , Ar has the same definition as given in claim 1 above; The preparation method is: (1) In an organic solvent, the compound of formula A, an aromatic amine and polyformaldehyde ((CH2O) n ) at the boiling point of the solvent for 15-30 hours to obtain a compound of formula I, wherein R 3 =H; the molar ratio of the compound of formula A, the arylamine and the paraformaldehyde is 1:1.2:2; the organic solvent is methanol, ethanol, propanol, isopropanol or tert-butanol; (2) Under argon protection, the R 3 =H, and 1.1 equivalents of R 4 The acyl chloride and 3.0 equivalents of base are reacted in an organic solvent at 0°C for 2-4 hours to obtain R 3 =R 4 CO is a compound of formula I; the base is sodium hydroxide, potassium hydroxide, potassium carbonate, cesium carbonate, potassium tert-butoxide, triethylamine or diisopropylethylamine; the organic solvent is dichloromethane, tetrahydrofuran or 1,4-dioxane.

7. Use of the xanthine derivative containing an aromatic amino group according to any one of claims 1 to 5 in preventing and controlling weeds, insect pests and pathogenic bacteria on various crops, characterized in that The use refers to the use for preparing agricultural herbicides, insecticides and fungicides.

8. The xanthine derivative containing an aromatic amino group according to any one of claims 1 to 5 as a KARI inhibitor.

9. Use of the xanthine derivative containing an aromatic amino group according to claim 7 for preparing agricultural herbicides, insecticides and fungicides, characterized in that The herbicide is a herbicide for killing rapeseed, Amaranthus retroflexus, barnyard grass or crabgrass, the insecticide is a pesticide for killing diamondback moth, and the fungicide is a fungicide for killing wheat fusarium, pepper phytophthora, rapeseed sclerotinia, cucumber wilt, apple ring rot or wheat sheath blight.

10. Use of the xanthine derivative containing an aromatic amino group according to claim 7 in preventing and controlling weeds, insect pests and pathogenic bacteria on various crops, characterized in that The use also includes the following steps: deriving the xanthine containing aromatic amino groups The compound is used as an active ingredient of a herbicidal, insecticidal or fungicidal composition for preparing agricultural herbicides, insecticides or fungicides; The herbicidal, insecticidal or fungicidal composition also includes an agricultural, forestry and hygienic acceptable carrier.

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