A xanthine derivative containing an arylamino group, and a preparation method and application thereof

Abstract

The present application relates to a kind of arylamino-containing xanthine derivatives and its preparation method and application.On the basis of 1,3-disubstituted xanthine raw material, arylamino-containing xanthine derivatives obtained by series of reactions are shown as general formula I.Compounds of general formula I have higher herbicidal activity, and have obvious activity on rape, amaranthus retroflexus, barnyard grass, crabgrass, have good insecticidal activity, especially on the effect of diamondback moth is remarkable, have good fungicidal activity, and have obvious in vitro inhibitory activity on wheat scab fungus, pepper phytophthora blight fungus, sclerotinia sclerotiorum, cucumber fusarium wilt fungus, apple phialophora quercina, wheat sharp eyespot fungus, etc.Compounds of general formula I can be used as active components of herbicidal or insecticidal or fungicidal composition, for preparing agricultural herbicide or insecticide or fungicide, and can be used for the prevention and treatment of grass damage or insect damage or pathogenic damage on various crops.Also have good inhibitory effect on the activity of KARI, and can be used for KARI inhibitor.

Description

Technical Field

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

[0002] The control of weeds, plant diseases, and pests is of great significance for the smooth operation of various industries, including agriculture, forestry, animal husbandry, sideline production, fisheries, and public health. Pesticides play a crucial role in this process. Finding highly active pesticides with novel structures and superior performance to increase crop yields and overcome the shortcomings of traditional pesticides is a long-term and arduous task.

[0003] Structural modification and optimization of bioactive natural products is a practical approach to designing and discovering new agrochemicals. Generally, compounds designed using this method are more likely to exhibit high bioactivity and good biocompatibility. Xanthine alkaloids, represented by theophylline (1,3-dimethylxanthine), caffeine, and theobromine, are widely found in various plants and have been found to possess potential insecticidal and antibacterial activities. These compounds are closely related to people's diets and often exhibit low toxicity. Research on these compounds has mainly focused on the pharmaceutical field, with various natural and synthetic xanthines and their derivatives used to treat neurodegenerative diseases, respiratory diseases, kidney diseases, cancer, and cardiovascular diseases. However, research and application of these compounds in the pesticide field are relatively limited and require further exploration. Therefore, research on structural modification and transformation of xanthine alkaloids to obtain novel, environmentally friendly, and highly efficient pesticide molecules has considerable development potential and application prospects. Furthermore, ketool acid reductase (KARI) is a key enzyme in the biosynthesis of branched-chain amino acids, existing only in plants and microorganisms. Herbicides and fungicides designed using KARI as pesticide targets theoretically have the advantage of safety for humans and mammals, aligning with the research direction of green pesticides. The synthesis and screening of new compounds that inhibit KARI activity is of great significance in the research and development of new pesticides. In the prior art, there is no publicly available method for preparing a xanthine derivative containing aromatic amino groups, as reported in this invention, nor is its application as an agricultural herbicide, insecticide, fungicide, and KARI inhibitor. Summary of the Invention

[0004] The purpose of this invention is to provide a novel xanthine derivative containing aromatic amino groups as an alternative to traditional agricultural herbicides, insecticides, or fungicides, along with its preparation method and uses. This derivative exhibits good herbicidal, insecticidal, and fungicidal activities and can be applied to the integrated control of diseases, pests, and weeds on various crops. Furthermore, this derivative also exhibits good KARI inhibitory activity. Therefore, this invention also includes the use of this derivative as a KARI inhibitor.

[0005] This invention provides a xanthine derivative containing an aromatic amino group, having the structural formula shown in general formula I:

[0006]

[0007] In the formula:

[0008] R 1 R 2 It is a C1-C6 alkyl or a halo-C1-C6 alkyl;

[0009] R 3 Is it H or has R 4 Acyl group (R) 4 C(=O)-), R 4 It is a C1-C6 alkyl, a halo-C1-C6 alkyl, an aryl or an aryl-substituted C1-C3 alkyl, wherein the hydrogen on the aryl ring may be further substituted by the following groups: halogen, C1-C6 alkyl, halo-C1-C6 alkyl, cyano, nitro, phenyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, C1-C6 alkylthio, halo-C1-C6 alkylthio, C2-C6 alkenyl, halo-C2-C6 alkenyl, C3-C6 alkynyl, halo-C3-C6 alkynyl, C2-C6 alkenyloxy, halo-C2-C6 alkenyloxy, C3-C6 alkynyloxy, halo-C3-C6 alkynyloxy, phenoxy, pyridoxy;

[0010] Ar is an aryl group, wherein the hydrogen on the aryl ring can be further substituted by the following groups: halogen, C1-C6 alkyl, halo-C1-C6 alkyl, cyano, nitro, phenyl, C1-C6 alkoxy, halo-C1-C6 alkoxy, C1-C6 alkylthio, halo-C1-C6 alkylthio, C2-C6 alkenyl, halo-C2-C6 alkenyl, C3-C6 alkynyl, halo-C3-C6 alkynyl, C2-C6 alkenyloxy, halo-C2-C6 alkenyloxy, C3-C6 alkynyloxy, halo-C3-C6 alkynyloxy, phenoxy, pyridoxy;

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

[0012] Halogens are fluorine, chlorine, bromine, or iodine;

[0013] The alkyl group can be a straight-chain, branched, or cycloalkyl group, wherein the cycloalkyl group includes cyclic chain form or alkyl form with 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, etc.

[0014] The aryl group is a phenyl or aromatic heterocyclic group, such as furanyl, thiophene, pyrrole, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, thiazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, or triazinyl groups.

[0015] Alkenyl groups are straight or branched chains with 2-6 carbon atoms and can have double bonds at any position, 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 groups;

[0016] The alkynyl group is a straight or branched chain with 3-6 carbon atoms and can have a triple bond at any position. Examples include propynyl, propynyl, 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 an alkoxy group is the same as that of an alkyl group as defined herein. Under this premise, an alkoxy group refers to a group with an oxygen atom attached to the end of an alkyl group, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, n-hexoxy, cyclopropoxy, cyclopropylmethoxy, cyclobutoxy, cyclobutylmethoxy, cyclopentoxy, cyclopentylmethoxy, or cyclohexoxy groups.

[0018] The carbon skeleton of an alkylthio group is the same as that of an alkyl group as defined herein. Under this premise, an alkylthio group refers to a group with a sulfur atom attached to the alkyl end, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, n-pentylthio, isopentylthio, n-hexylthio, cyclopropylthio, cyclopropylmethylthio, cyclobutylthio, cyclobutylmethylthio, cyclopentylthio, cyclopentylmethylthio, or cyclohexylthio, etc.

[0019] The carbon skeleton of the olefin group is the same as that of the alkenyl group as defined above. Under this premise, the olefin group refers to the group with an oxygen atom attached to the end of the alkenyl group, such as ethyleneoxy group, allyloxy group, etc.

[0020] The carbon skeleton of the alkynyl group is the same as that of the alkynyl group as defined above. Under this premise, the alkynyl group refers to a group with an oxygen atom attached to the end of the alkynyl group, such as propynyloxy group.

[0021] Haloalkyl is a straight-chain alkyl, branched alkyl, or cycloalkyl, in which hydrogen atoms may be partially or completely replaced by halogen atoms; the definitions of "haloalkoxy", "haloalkylthio", "haloalkenyl", "haloalkynyl", "haloalkenoxy" and "haloalkynoxy" are similar to the term "haloalkyl".

[0022] The term "can be further replaced" refers to the fact that the number of substituents can be one or more.

[0023] The method for preparing 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] In the formula R 1 R 2 R 3 R 4 Unless otherwise specified, Ar is as defined above;

[0026] The preparation method is as follows:

[0027] 1) In organic solvents, compounds of formula A react with aryl amines and paraformaldehyde ((CH2O)). n The compound of formula I is obtained by reacting at the solvent boiling point temperature for 15-30 hours, wherein R 3 =H; the molar ratio of compound A, arylamine, and paraformaldehyde is 1:1.2:2; the organic solvent is methanol, ethanol, propanol, isopropanol, or tert-butanol;

[0028] 2) Under argon protection, the R obtained in step 1) is... 3 Compounds of formula I with H and 1.1 equivalents of R 4 The acyl chloride and 3.0 equivalents of base were reacted in an organic solvent at 0°C for 2-4 hours to give R. 3 =R 4 The compound of formula I of CO, wherein the substituents are as specified 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 general formula I of this invention exhibits high herbicidal activity, showing significant effects against dicotyledonous plants such as rapeseed and amaranth, as well as monocotyledonous plants such as barnyard grass and crabgrass. The compound of general formula I of this invention also exhibits good insecticidal activity against diamondback moth and other similar pests. Furthermore, the compound of general formula I of this invention shows good in vitro inhibitory activity against Fusarium graminearum (wheat scab), Phytophthora capsulatum (capsicum), Sclerotinia sclerotiorum (rapeseed), Fusarium wilt (cucumber), Alternaria alternata (apple ring rot), and Rhizoctonia solani (wheat sheath blight). Simultaneously, the compound of general formula I also exhibits good inhibitory activity against KARIs. Therefore, this invention also includes the use of the compound of general formula I for controlling weeds, insect pests, and pathogens on various crops, as well as its use as a KARI inhibitor.

[0030] The present invention also includes herbicidal, insecticidal, or fungicidal compositions using a compound of general formula I as the active ingredient, which can be used to prepare agricultural herbicides, insecticides, or fungicides. The herbicidal, insecticidal, or fungicidal compositions also include an agriculturally, forestryly, or sanitarily acceptable carrier.

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

[0032] This invention provides a novel xanthine derivative containing aromatic amino groups (compound of general formula I). ​​This derivative exhibits good herbicidal, insecticidal, fungicidal, and KARI inhibitory activities. It has excellent control effects on weeds such as rapeseed, amaranth, barnyard grass, and crabgrass; pests such as diamondback moth; and crop pathogens such as Fusarium head blight of wheat, Phytophthora capsici, Sclerotinia sclerotiorum of rapeseed, Fusarium wilt of cucumber, ring rot of apple, and sheath blight of wheat. It can be used as an active ingredient in herbicidal, insecticidal, or fungicidal compositions for the preparation of agricultural herbicides, insecticides, or fungicides, and can be used for the control of weeds, insects, or pathogens. Furthermore, it has a good inhibitory effect on KARI activity and can be used as a KARI inhibitor. Detailed Implementation

[0033] The present invention will be further illustrated below with reference to specific embodiments. The purpose of these embodiments is to provide a better understanding of the invention and to demonstrate its essential characteristics. Therefore, the examples given should not be considered as limitations on the scope of protection of the present invention. It is also specifically noted that, unless otherwise specified, the specific experimental methods and equipment involved in the embodiments are conventional methods or implemented according to the conditions recommended in the manufacturer's instructions, and the reagents involved are all 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 in the following equation:

[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. After natural cooling, the mixture was filtered to obtain the filtrate. After desolvation under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid. The precipitate was then filtered, washed, and dried to obtain compound I-1, a yellow solid, with a yield of 42%.

[0040] Example 2

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

[0042] The reaction route is shown in the following equation:

[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. After natural cooling, the mixture was filtered to obtain the filtrate. After desolvation under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid. The precipitate was then filtered, washed, and dried to obtain compound I-2, a yellow solid, in 40% yield.

[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 in the following equation:

[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. After natural cooling, the mixture was filtered to obtain the filtrate. After desolvation under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid. The precipitate was then filtered, washed, and dried to obtain compound I-9, a yellow solid, in 33% yield.

[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 in the following equation:

[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. After natural cooling, the mixture was filtered to obtain the filtrate. After desolvation under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid. The precipitate was then filtered, washed, and dried to obtain compound I-13, a white solid, in 41% yield.

[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 in the following equation:

[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. After natural cooling, the mixture was filtered to obtain the filtrate. After desolvation under reduced pressure, an appropriate amount of water was added to the residue to precipitate a solid. The precipitate was then filtered, washed, and dried to give 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-purine-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. Chloroacetyl chloride (1.1 mmol) was added under an argon atmosphere at 0 °C, and the reaction mixture was continuously stirred magnetically at 0 °C for 3 hours. The reaction mixture was washed with 10 mL of water, and the organic phase was separated and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated to obtain a crude product. Column chromatography (dichloromethane / methanol, v / v = 120:1) was used to purify the crude product, yielding 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-purine-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. Chloroacetyl chloride (1.1 mmol) was added under an argon atmosphere at 0 °C, and the reaction mixture was continuously stirred magnetically at 0 °C for 3 hours. The reaction mixture was washed with 10 mL of water, and the organic phase was separated and dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated to obtain a crude product. Column chromatography (dichloromethane / methanol, v / v = 120:1) was used to purify the crude product, yielding compound I-22 as a white solid in 35% yield.

[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-purine-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. Chloroacetyl chloride (1.1 mmol) was added under an argon atmosphere at 0 °C, and the reaction mixture was continuously stirred magnetically at 0 °C for 3 hours. The reaction system was washed with 10 mL of water, the organic phase was separated, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain the crude product. The crude product was purified by column chromatography (dichloromethane / methanol, v / v = 120:1) to give compound I-24, a white solid, in 31% yield.

[0076] Tables 1a and 1b below list the structures and physical properties of some compounds of general formula I.

[0077] Table 1a shows the structure and physical properties of some compounds of general formula I.

[0078]

[0079]

[0080] Table 1b shows the structure and physical properties of some compounds of general formula I.

[0081]

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

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

[0084]

[0085]

[0086]

[0087]

[0088]

[0089]

[0090] Examples of bioactivity testing for compounds of general formula I

[0091] Example 9

[0092] The herbicidal activity of the compounds provided by this invention was determined.

[0093] (1) Plate method: Using rapeseed (Brassica campestris) as the test object, a 5.6 cm diameter filter paper was placed in a 6 cm diameter petri dish, and 2 mL of the test compound solution with a concentration of 100 μg / mL or 10 μg / mL was poured in (the compound was dissolved in DMF and then diluted with distilled water to the required concentration). 15 rapeseed seeds that had been soaked in distilled water for 4 hours were added to the petri dish. The petri dish was then placed at 28±1℃ and cultured in the dark for 65 hours. The length of the radicle was then measured. The herbicidal activity of the compound was detected by inhibiting the growth of the rapeseed radicle under dark conditions. The inhibition rate was obtained by comparing the compound with the blank control.

[0094] (2) Small cup method: Using barnyard grass (Echinochloa crus-galli) as the test object, glass beads and filter paper were placed in a 50 mL beaker, and 6 mL of the test compound solution with a concentration of 100 μg / mL or 10 μg / mL was poured in (the compound was dissolved in DMF and then diluted with distilled water to the required concentration). Ten barnyard grass seeds that had just sprouted were added to the beaker. The beaker was then placed at 28±1℃ and cultured under light for 65 hours. The height of the seedlings was then measured. The herbicidal activity of the compound was detected by inhibiting the growth of barnyard grass seedling height under light conditions. The inhibition rate was obtained by comparing the compound with the blank control.

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

[0096] Table 3 shows the growth inhibition rates of some compounds of general formula I on rapeseed and barnyard grass.

[0097]

[0098]

[0099] (3) Pot method: Using rapeseed (Brassica campestris), amaranth (Amaranthus retroflexus), barnyard grass (Echinochloa crus-galli), and crabgrass (Digitaria adscendens) as test subjects, a fixed amount of soil was placed in 7.0 cm diameter paper cups, an appropriate amount of water was added, and after sowing, a fixed thickness of soil was added. The plants were then moved to a greenhouse for cultivation. Before seedling emergence, the seedlings were covered with plastic sheeting, and a fixed amount of water was applied daily to maintain normal plant growth. The experiment was divided into soil treatment (conducted before seedling emergence, i.e., spraying the soil with different corresponding doses of herbicide before sowing) and foliar treatment (conducted after seedling emergence, i.e., spraying the stems and leaves with different corresponding doses of herbicide during the seedling stage). The experimental results were investigated 15 days after treatment, and the fresh weight of the above-ground parts was measured. The fresh weight inhibition rate was calculated by comparing the results with the untreated group to measure the herbicidal effect of the compound.

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

[0101] Table 4 shows the herbicidal activity of some compounds of general formula I.

[0102]

[0103]

[0104] Example 10

[0105] The insecticidal activity of the compounds provided by this invention was determined.

[0106] Bioactivity assay against diamondback moth (Plutella xylostella Linnaeus): The insecticidal activity against diamondback moth was tested using the leaf-dip method. The test compound was dissolved in 1 mL of DMF, then diluted with distilled water to prepare a solution of the corresponding test concentration. Cabbage leaves (5 × 1 cm) were then immersed in the solution for 3–5 seconds. After removing the excess solution and allowing the leaves to dry, they were placed in 10 cm long test tubes and inoculated with 10 second-instar diamondback moth larvae. Three groups were prepared for each sample, and the room temperature was maintained at 25 ± 1℃. The blank control consisted of larvae reared by immersing cabbage leaves in a diluted DMF solution. Results were recorded after 72 hours. Inactivity was considered the mortality criterion for larvae. The lethality of the test compound against diamondback moth larvae was assessed using a range of 0–100% (lethality rate), where 0% indicated no insecticidal effect and 100% indicated complete killing.

[0107] The results of the above insecticidal activity tests are shown in Table 5.

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

[0109]

[0110]

[0111] Example 11

[0112] The bactericidal activity was tested using the compound of general formula I provided by this invention.

[0113] Determination of bactericidal activity using the in vitro agar plate method: *Fusarium graminearum* (wheat scab), *Phytophthora capsici* (pepper causal agent), *Sclerotinia sclerotiorum* (rapeseed sclerotinia rot), *Fusarium wilt* (cucumber wilt), *Rhizoctonia solani* (apple ring rot), and *Rhizoctonia solani* (wheat sheath blight) were used as test targets. The test compounds were dissolved in DMSO to prepare a concentration of 1.0 × 10⁻⁶. 4 A 50 mg / L test solution was prepared by diluting the 50 mg / L solution with Tween solution. Under aseptic conditions, 1.0 mL of the test solution was added to 9 mL of PDA medium, and the test strain was inoculated. A blank control was prepared using medium with 1 mL of sterile water. The medium was incubated at 25 ± 1 °C for 72 h. The colony diameter was then measured and compared with that of the blank test to calculate the inhibition rate.

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

[0115] Inhibition rates against Fusarium graminearum: I-10 55.6%, I-15 36.1%, I-19 35.0%;

[0116] Inhibition rates against Phytophthora capsici: 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 rates against cucumber wilt pathogens: 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] Inhibition rates against wheat sheath blight fungus: 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 was tested using the compound of general formula I provided by this invention.

[0123] Test Methods: KARI was expressed in large quantities in *E. coli* cells transformed with a recombinant plasmid (containing the rice KARI gene). The interaction between the compound and KARI was studied under in vitro conditions. A dynamic analysis method was used. Appropriate amounts of inhibitor solution, 0.1 mol / L Tris-HCl buffer (pH 8.0), 0.2 mmol / L NADPH, 1 mmol / L MgCl2, and an appropriate amount of rice KARI protein were mixed in a cuvette and incubated at 30°C for 10 minutes. A mixture containing 0.1 mmol / L acetolactate was added to initiate the enzyme reaction. The slope of the initial linear change (ΔOD) was used as the starting point for the reaction. 340 The initial enzyme activity was represented by absorbance at 340 nm ( / min). The absorbance was continuously recorded at 340 nm (to monitor the reduction of NADPH) to obtain the inhibition curve of the inhibitor on KARI enzyme activity. The inhibition rate was then calculated by comparing it with the blank control. The results are shown in Table 6.

[0124] Table 6 shows the 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 a structural formula as shown in general formula I: In the formula: R 1 R 2 It is a C1-C6 alkyl group; When R 3 When H is present, Ar is 2-methylphenyl, 4-methylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 4-chloro-2-methoxyphenyl, pyrimidinyl or 2-chloropyridin-3-yl, wherein the hydrogen on the pyrimidinyl ring can be further substituted by C1-C6 alkyl groups; When R 3 It is R 4 When C(=O)-, R 4 It is a halogenated C1-C6 alkyl group, Ar is phenyl, and the hydrogen on the phenyl ring can be further replaced by the following groups: halogen, C1-C6 alkyl, C1-C6 alkoxy.

2. The xanthine derivative containing an aromatic amino group according to claim 1, characterized in that: The halogen is fluorine, chlorine, bromine or iodine; The alkyl group specifically includes 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 alkoxy group specifically includes methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, n-hexyloxy, cyclopropoxy, cyclopropylmethoxy, cyclobutoxy, cyclobutylmethoxy, cyclopentoxy, cyclopentylmethoxy, or cyclohexyloxy. 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 replaced by halogen atoms; The term "can be further replaced" refers to the fact that the number of substituents can be one or more.

3. A xanthine derivative containing an aromatic amino group according to claim 2, characterized in that: R 1 R 2 It is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl, isopentyl, n-hexyl, isohexyl, cyclopropyl or cyclopropylmethyl; When R 3 When H is present, Ar is 2-methylphenyl, 4-methylphenyl, 4-fluorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 4-chloro-2-methoxyphenyl, pyrimidin-2-yl, 4,6-dimethylpyrimidin-2-yl, or 2-chloropyridin-3-yl; When R 3 It is R 4 When C(=O)-, R 4 The group is a halogenated methyl group, a halogenated ethyl group, a halogenated n-propyl group, a halogenated isopropyl group, a halogenated n-butyl group, a halogenated isobutyl group, a halogenated sec-butyl group, a halogenated tert-butyl group, a halogenated n-pentyl group, a halogenated isopentyl group, a halogenated n-hexyl group, a halogenated isohexyl group, a halogenated cyclopropyl group, a halogenated cyclobutyl group, a halogenated cyclopentyl group, a halogenated cyclohexyl group, or a halogenated cyclopropylmethyl group, where Ar is a phenyl group. The hydrogen on the phenyl 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, methoxy, ethoxy, n-propoxy, isopropoxy; the group can be further substituted, and the number of substituents can be one or more.

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

5. The method for preparing the xanthine derivative containing aromatic amino groups according to claim 1, characterized in that... Prepared by the following method: In the formula R 1 R 2 R 3 R 4 Ar has the same definition given in claim 1 above; The preparation method is as follows: (1) In an organic solvent, the compound of formula A reacts with an aryl amine and paraformaldehyde at the solvent boiling point temperature for 15-30 hours to obtain the compound of formula I, wherein R 3 = H; the molar ratio of compound A, arylamine, and paraformaldehyde is 1:1.2:2; the organic solvent is methanol, ethanol, propanol, isopropanol, or tert-butanol; (2) Under argon protection, the R obtained in step (1) is... 3 = H, the compound of formula I and 1.1 equivalents of R 4 The acyl chloride and 3.0 equivalents of base were reacted in an organic solvent at 0°C for 2-4 hours to give R. 3 = R 4 The compound of formula I of CO; 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.

6. The use of the xanthine derivative containing aromatic amino groups according to any one of claims 1-4 in the preparation of agricultural herbicides, insecticides, and fungicides, characterized in that... The herbicide is a herbicide that kills rapeseed, amaranth, barnyard grass, or crabgrass; the insecticide is an insecticide that kills diamondback moth; and the fungicide is a fungicide that kills Fusarium graminearum, Phytophthora capsici, Sclerotinia sclerotiorum, Fusarium wilt, Rhizoctonia solani, or Rhizoctonia solani.

7. Use of the aromatic amino-containing xanthine derivative according to any one of claims 1-4 in the preparation of KARI inhibitors.

8. The use of the xanthine derivative containing aromatic amino groups according to claim 6 in the preparation of agricultural herbicides, insecticides, and fungicides, characterized in that... The uses also include using the aromatic amino-containing xanthine derivative as an active ingredient in a herbicidal, insecticidal, or fungicidal composition for the preparation of agricultural herbicides, insecticides, or fungicides; the herbicidal, insecticidal, or fungicidal composition also includes an agriculturally, forestryly, and sanitarily acceptable carrier.

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