Pyrimidine compounds and their application in inhibiting plant pathogenic fungi

Abstract

This invention relates to pyrimidine compounds and their application in inhibiting plant pathogenic fungi. The chemical structural formula of the pyrimidine compounds of this invention is shown in Formula I), wherein R is selected from H or R1CO; and R1 is selected from alkyl, haloalkyl, phenyl, and substituted phenyl groups. The compounds of this invention can be used for the control of plant pathogenic fungal diseases, wherein the plant pathogenic fungus can be Fusarium graminearum (…). Fusarium gramineae ), Apple black rot fungus ( The waltz of evil ), Sclerotinia sclerotiorum ( Sclerotinia sclerotia ) or Staphylococcus aureus ( Botryosphaeria dothidae ), formula I).

Description

Technical Field

[0001] This invention relates to the field of hybrid compounds, and particularly to bactericidal compounds. Background Technology

[0002] Wheat scab is mainly caused by Fusarium graminearum, a fungus belonging to the Ascomycota phylum and the Tuberculaceae family. Fusarium graminearum Apple rot is caused by *Sphaerophyte macrantha*, a fungus belonging to the family Ascomycota, family Ascomycetes. Valsa mali Sclerotinia rot in rapeseed is caused by *Sclerotinia sclerotiorum*, a fungus belonging to the Ascomycota phylum. Sclerotinia sclerotiorum Apple ring rot is caused by *Staphylococcus aureus*, a fungus belonging to the family Staphylococcidaceae within the phylum Ascomycota. Botryosphaeria dothidea )cause.

[0003] With the increasing prominence of problems such as the aggravation of pathogen resistance caused by long-term use of single drugs, there is an urgent need to develop new bactericides with novel structures, excellent activity, and high safety. Summary of the Invention

[0004] One aspect of the present invention provides a pyrimidine compound or a pesticide-acceptable salt thereof, the chemical structural formula of which is shown in Formula I). Formula I), Wherein, R is selected from H or R1CO; and R1 is selected from one of alkyl, haloalkyl, phenyl and substituted phenyl.

[0005] In one specific embodiment, the alkyl group is one of C1 to C4 alkyl groups.

[0006] In one specific embodiment, the halogenated group is selected from one of fluorinated, chloro, and brominated groups.

[0007] In one specific embodiment, the substituted phenyl group is selected from at least one of alkylphenyl, halophenyl, nitrophenyl, alkoxyphenyl, and haloalkylphenyl.

[0008] In one specific embodiment, R1 is selected from at least one of chloromethyl, phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-bromophenyl, 4-bromophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, and 4-methoxyphenyl.

[0009] The second invention provides a method for preparing the compound according to the first invention, which includes first reacting 2-chloropyrimidine and 4-nitrophenylboronic acid to generate 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine, and then reducing 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine to generate a compound in which R is H as in the compound of the first invention.

[0010] The third invention provides a method for preparing the compound according to any one of the inventions, wherein a compound in which R is H in the compound according to any one of the inventions reacts with a substituted acid in the presence of a condensing agent to generate a compound in which R is R1CO in the compound according to any one of the inventions.

[0011] In one specific embodiment, the substituted acid is selected from alkyl acids, haloalkyl acids, benzoic acid, and substituted benzoic acid.

[0012] In one specific embodiment, the substituted acid is selected from benzoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, 3-chlorobenzoic acid, 4-chlorobenzoic acid, 3-bromobenzoic acid, 4-bromobenzoic acid, 3-nitrobenzoic acid, 4-nitrobenzoic acid, 4-methylbenzoic acid, 4-trifluoromethylbenzoic acid, 4-methoxybenzoic acid, and 2-chloroacetic acid.

[0013] In one specific embodiment, the preparation method includes the following steps: 1) 2-chloropyrimidine, 4-nitrophenylboronic acid, a first palladium catalyst and a first solvent are mixed and reacted under a first alkaline condition and a first inert gas atmosphere at a first temperature for a first duration to obtain a first reactant containing 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine; 2) The 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine was isolated and purified from the first reactant; 3) The 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine, the second palladium catalyst, and the second solvent are mixed and reacted at a second temperature for a second duration under a hydrogen atmosphere to obtain a second reactant containing a compound in which R is H as described in one of the present invention; 4) The compound with R being H in the compound as described in one of the present invention is isolated and purified from the second reactant.

[0014] In one specific embodiment, the molar ratio of 2-chloropyrimidine to 4-nitrophenylboronic acid is 1:(0.5 to 3).

[0015] In one specific embodiment, the molar ratio of 2-chloropyrimidine to 4-nitrophenylboronic acid is 1:(1.1 to 1.5), for example 1:1.2.

[0016] In one specific embodiment, the molar ratio of 2-chloropyrimidine to 4-nitrophenylboronic acid is 1:(1.1 to 1.2).

[0017] In one specific embodiment, the molar ratio of 2-chloropyrimidine to the first palladium catalyst is 1:(0.01 to 1).

[0018] In one specific embodiment, the molar ratio of 2-chloropyrimidine to the first palladium catalyst is 1:(0.5 to 0.7).

[0019] In one specific embodiment, the pH value of the first alkaline condition is 7.2 to 14.

[0020] In one specific embodiment, the first alkaline condition is adjusted by a first alkaline regulator, and the molar ratio of 2-chloropyrimidine to the first alkaline regulator is 1:(0.5 to 5). Further, the molar ratio of 2-chloropyrimidine to the first alkaline regulator is 1:(1 to 1.5).

[0021] In one specific embodiment, the molar ratio of 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine to the second palladium catalyst is 1:(0.1 to 2).

[0022] In one specific embodiment, the preparation method includes the following steps: I) The compound in which R is H in any one of the compounds of the present invention, the substituted acid, the condensing agent and the third solvent are mixed and reacted under a second alkaline condition and a second inert gas atmosphere at a third temperature for a third duration to obtain a third reactant containing a compound in which R is R1CO in any one of the compounds of the present invention. II) Separate and purify from the third reactant a compound in which R is R1CO, as described in any one of the present invention.

[0023] In one specific embodiment, the molar ratio of the compound with R being H to the substituted acid in the compound as described in one of the present invention is 1:(0.5 to 3).

[0024] In one specific embodiment, the molar ratio of the compound with R being H to the substituted acid in the compound as described in one of the present invention is 1:(1.1 to 1.5), for example 1:(1.1 to 1.2).

[0025] In one specific embodiment, the molar ratio of the compound with R being H in the compound described in one of the present invention to the condensing agent is 1:(1 to 1.5), for example 1:(1.2 to 1.25).

[0026] In one specific embodiment, the molar ratio of the compound with R being H in one of the compounds described in this invention to the catalyst is 1:(0.5 to 1), for example 1:1.

[0027] In one specific embodiment, the first palladium catalyst is selected from at least one of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), palladium chloride (PdCl2), and 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride (PdCl2(dppf)).

[0028] In one specific embodiment, the second palladium catalyst is selected from palladium hydroxide on carbon catalyst and palladium metal on carbon.

[0029] In one specific embodiment, the condensing agent is selected from one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), 2-(7-azobenzotriazole)-tetramethylurea hexafluorophosphate (HATU), N,N-dicyclohexylcarbodiimide (DCC), and N,N'-diisopropylcarbodiimide (DIC).

[0030] In one specific embodiment, the first solvent is a mixture of water and ethanol. For example, the first solvent is a mixture of water and ethanol in a volume ratio of 1:8.

[0031] In one specific embodiment, the second solvent is tetrahydrofuran and / or chloroform.

[0032] In one specific embodiment, the third solvent is dichloromethane and / or N,N-dimethylformamide.

[0033] In one specific embodiment, the first alkaline condition is adjusted by at least one of sodium hydroxide, cesium carbonate, sodium bicarbonate, sodium acetate, sodium carbonate, potassium carbonate, and potassium acetate.

[0034] In one specific embodiment, the second alkaline condition is adjusted by triethylamine and / or diisopropylethylamine.

[0035] In one specific embodiment, the first inert gas is nitrogen.

[0036] In one specific embodiment, the second inert gas is nitrogen.

[0037] In one specific embodiment, the first temperature is -20 to 100 degrees Celsius.

[0038] In one specific embodiment, the second temperature is 0 to 80 degrees Celsius.

[0039] In one specific embodiment, the third temperature is -20 to 50 degrees Celsius.

[0040] In one specific implementation, the first duration is 1 to 20 hours.

[0041] In one specific implementation, the second duration is 0.5 to 10 hours.

[0042] In one specific implementation, the third duration is 1 to 20 hours.

[0043] In one specific embodiment, the first temperature is 80 to 100 degrees Celsius.

[0044] In one specific embodiment, the second temperature is 5 to 40 degrees Celsius.

[0045] In one specific embodiment, the third temperature is 5 to 40 degrees Celsius.

[0046] In one specific implementation, the first duration is 8 to 12 hours.

[0047] In one specific implementation, the second duration is 1 to 5 hours.

[0048] In one specific implementation, the third duration is 8 to 12 hours.

[0049] In one specific embodiment, 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine is purified from the first reactant by rotary evaporation, extraction, drying, vacuum concentration, and column chromatography.

[0050] In one specific embodiment, after removing the solvent from the first reactant by rotary evaporation, water is added and then extracted with dichloromethane. The mixture is dried with anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography using petroleum ether and ethyl acetate in a volume ratio of 10:1 to obtain 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine.

[0051] In one specific embodiment, compounds with R being H in the compounds described in one of the present invention are purified from the second reactant by filtration, rotary evaporation, and column chromatography.

[0052] In one specific embodiment, compounds in which R is R1CO, as described in any one of the present invention, are purified from the third reactant by extraction, drying, vacuum concentration, and column chromatography.

[0053] In one specific embodiment, the organic phase is extracted from the third reactant with dichloromethane, dried with anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography using petroleum ether and ethyl acetate as the mobile phase to obtain a compound in which R is R1CO as described in any one of the present invention.

[0054] In one specific embodiment, step I) optionally includes a catalyst selected from dimethylaminopyridine and / or 1-hydroxybenzotriazole (HOBt).

[0055] The fourth invention provides a bactericidal composition comprising a compound according to any one of the first inventions, a compound prepared by the preparation method according to the second invention, or a compound prepared by the preparation method according to any one of the third inventions, and a pesticide-acceptable adjuvant.

[0056] In one specific embodiment, the composition is a bactericide emulsifiable concentrate or a bactericide wettable powder.

[0057] In one specific embodiment, the additive is selected from at least one of emulsifiers, penetrants, and solvents.

[0058] In one specific embodiment, the emulsifier may be a surfactant, such as at least one of agricultural emulsion 0208, agricultural emulsion 300#, agricultural emulsion 0203B and Tween-60; the solvent may be toluene and / or xylene.

[0059] In one specific embodiment, the additive is selected from surfactants and / or wettable powder carriers. The surfactant may be NNO; the wettable powder carrier may be silica.

[0060] In one specific embodiment, the bactericidal composition is a bactericidal emulsifiable concentrate, and the content of the compound prepared by the preparation method according to any one of the first invention or any one of the second or third invention, based on the total mass of the bactericidal emulsifiable concentrate, is 1% to 10%, the content of the emulsifier is 5% to 15%, the content of the penetrant is 0.1% to 1%, and the balance is solvent.

[0061] In one specific embodiment, the bactericidal composition is a wettable powder of bactericide, and the content of the compound prepared by the preparation method according to any one of the first invention or any one of the second or third invention, based on the total mass of the wettable powder of bactericide, is 15% to 50%, the content of the surfactant is 10% to 20%, and the content of precipitated silica is 30% to 75%.

[0062] The fifth invention provides the use of compounds according to any one of the first invention, compounds prepared by any one of the preparation methods according to the second or third invention, or compositions according to the fourth invention in the inhibition of plant pathogenic fungi.

[0063] In one specific embodiment, the plant pathogenic fungus is Fusarium graminearum (Fusarium graminearum). Fusarium graminearum ), Apple black rot fungus ( Valsa mali ), Sclerotinia sclerotiorum ( Sclerotinia sclerotiorum ) and Staphylococcus aureus ( Botryosphaeria dothidea At least one of the following.

[0064] In one specific embodiment, the compound of the present invention is used to control at least one of wheat scab, apple rot, rapeseed sclerotinia stem rot, apple ring rot, pepper blight, tomato early blight, rice sheath blight, cotton damping-off, tomato late blight, tomato gray mold, and cotton wilt.

[0065] The beneficial effects of this invention: The pyrimidine compounds of this invention have antifungal activity and can be used for the prevention and control of plant pathogenic fungal diseases, wherein the plant pathogenic fungi may be, for example, Fusarium graminearum (…). Fusarium graminearum ), Apple black rot fungus ( Valsa mali ), Sclerotinia sclerotiorum ( Sclerotinia sclerotiorum ) or Staphylococcus aureus ( Botryosphaeria dothidea ). Attached Figure Description

[0066] Figure 1 The proton NMR spectrum of PPI-A0 is shown (300 MHz, CDCl3).

[0067] Figure 2 The proton NMR spectrum of PPI-A2 is shown (300 MHz, CDCl3). Detailed Implementation

[0068] The present invention will be further described in detail below through preferred embodiments, but these embodiments do not constitute a limitation thereof.

[0069] Unless otherwise specified, the reagents and strains used in the embodiments of this invention can be purchased commercially.

[0070] Fusarium graminearum ( Fusarium graminearum ), Apple black rot fungus ( Valsa mali ), Sclerotinia sclerotiorum ( Sclerotinia sclerotiorum ) and Staphylococcus aureus ( Botryosphaeria dothidea All of these materials were provided by the College of Science, China Agricultural University. Example 1: Preparation of compound PPI-A0 from 2-chloropyrimidine

[0071]

[0072] 1) Compound 2-chloropyrimidine (1.7 g, 10.0 mmol), 4-nitrophenylboronic acid (2.0 g, 12 mmol), tetrakis(triphenylphosphine)palladium (Pd(PPh3)4, 0.8 g, 0.7 mmol), sodium carbonate (1.3 g, 12 mmol), ethanol (40 mL) and water (5 mL) were added to a round-bottom flask. The mixture was stirred at 90 °C for 10 hours under a nitrogen atmosphere to obtain the first reactant. The reaction was confirmed to be complete by thin-layer chromatography using petroleum ether and ethyl acetate in a volume ratio of 3:1 as the developing solvent.

[0073] 2) Remove the solvent from the first reactant by rotary evaporation, add 100 mL of deionized water, and extract three times with 50 mL of dichloromethane each time. Combine the organic phases extracted three times to obtain the first combined organic phase.

[0074] 3) The first combined organic phase was dried over anhydrous sodium sulfate to remove water, concentrated under reduced pressure, and purified by column chromatography using petroleum ether to ethyl acetate (volume ratio 10:1) as the mobile phase to obtain 2.1 g of the first compound, with a calculated yield of 82%. The first compound was detected using a Bruker AVANCE 600 spectrometer with nuclear magnetic resonance. 1 The H NMR results are as follows: (300 MHz, CDCl3) δ 8.59 (d, J = 9.0 Hz, 2H), 8.27 (d, J = 9.0Hz, 2H), 6.99 (s, 1H), 2.54 (s, 3H), 2.05-1.93 (m, 1H), 1.30-1.21 (m, 2H), 1.13-1.07 (m, 2H). ESI-MS [M+H] + 256.76, this result indicates that the first compound is 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine.

[0075] 4) Compound 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine (2 g, 7.8 mmol), palladium on carbon (Pd / C, 1.0 g) and tetrahydrofuran (70 mL) were placed in a round-bottom flask and reacted under H2 atmosphere for 2 hours to obtain the second reactant. The second reactant was analyzed by thin-layer chromatography using petroleum ether and ethyl acetate in a volume ratio of 3:1 as the developing solvent to confirm that the reaction was complete.

[0076] 5) The second reactant was filtered, concentrated by rotary evaporation, and purified by column chromatography using petroleum ether to ethyl acetate at a volume ratio of 5:1 as the mobile phase, yielding 1.4 g of the second compound as a white solid. The calculated yield was 80%. The second compound was analyzed using a Bruker AVANCE 600 spectrometer with nuclear magnetic resonance (NMR). The 1H NMR spectrum is shown below. Figure 1 , 1 The 1H NMR results are as follows: (300 MHz, CDCl3) δ 8.36 – 8.18 (m, 2H), 6.80 (s, 1H), 6.76 – 6.70 (m, 2H), 3.88 (s, 2H), 2.48 (s, 3H), 2.00 – 1.88 (m, 1H), 1.27 – 1.18 (m, 2H), 1.08 – 0.99 (m, 2H); HRMS (ESI) calcd for C 14 H 16 N3(M+H + ) 226.1344, found 226.1339. The results showed that the second compound was 4-(4-cyclopropyl-6-methylpyrimidin-2-yl)aniline, which was designated PPI-A0. Comparative Example 1: An attempt was made to prepare the intermediate product of compound PPI-A0 using 1-cyclopropyl-1,3-butanedione and p-nitrobenzomidine as starting materials.

[0077] Using 1-cyclopropyl-1,3-butanedione and p-nitrobenzomidine as raw materials, the intermediate product 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine, which is used to prepare PPI-A0, was not obtained under different reaction conditions as shown in Table 1.

[0078]

[0079] Table 1 Comparative Example 2: An intermediate product of compound PPI-A0 was prepared using 1-cyclopropyl-1,3-butanedione, nitrobenzaldehyde, and ammonium acetate as raw materials.

[0080]

[0081] The comparative example attempted to prepare the intermediate product of compound PPI-A0 with reference to the following literature: C. Rakhi, K. Ramesh, MP Darbem, TA Branquinho, AR de Oliveira, PS Manjari, NLCDomingues, Novel multi-component syntheses of pyrimidines using β-CD inaqueous medium, Tetrahedron Lett., 57(15) (2016), pp. 1656-1660.

[0082] 10 mmol of β-cyclodextrin was dissolved in 10 mL of water and heated to 65°C. Then, 1.0 mmol of p-nitrobenzaldehyde was added, and the reaction was allowed to proceed for 10 minutes. Next, ammonium acetate (2.0 mmol, 154 mg) and 1-cyclopropyl-1,3-butanedione (1.0 mmol, 126 mg) were added to the reaction mixture, and the mixture was stirred at 65°C for 10 hours. After the reaction was complete, the system was cooled to room temperature and extracted three times with 20 mL of ethyl acetate each time. The organic phases from the three extractions were combined, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and then purified by column chromatography to obtain 106 mg of the compound as a pale yellow oily liquid. The calculated yield was 41%. The compound was detected using a Bruker AVANCE 600 spectrometer with nuclear magnetic resonance. 1 The H NMR results are as follows: (300 MHz, CDCl3) δ 8.23 ​​(d, J = 9.0 Hz, 2H), 7.69– 7.55 (m, 3H), 2.42 (s, 3H), 2.04 – 1.91 (m, 1H), 1.31 – 1.22 (m, 2H), 1.10– 0.98 (m, 2H). ESI-MS [M+H] + 260.55. The results showed that the compound was 1-cyclopropyl-2-(4-nitrobenzyl)butane-1,3-dione, meaning that the intermediate 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine used to prepare PPI-A0 could not be synthesized using 1-cyclopropyl-1,3-butanedione, nitrobenzaldehyde, and ammonium acetate as raw materials. Example 2: Preparation and structural identification of compound PPI-A2

[0083]

[0084] 1) PPI-A0 (225 mg, 1 mmol), 2-fluorobenzoic acid (154 mg, 1.1 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 240 mg, 1.25 mmol), dimethylaminopyridine (122 mg, 1 mmol), triethylamine (277 μL, 2 mmol) and anhydrous dichloromethane (5 mL) were added to a flask. The mixture was stirred at room temperature under a nitrogen atmosphere for 10 hours. The reaction was confirmed to be complete by thin-layer chromatography with a petroleum ether to ethyl acetate volume ratio of 3:1. The reaction was quenched with 30 mL of water to obtain the third reactant.

[0085] 2) Extract the third reactant twice with 20 mL of dichloromethane each time, and combine the organic phases extracted twice to obtain the second combined organic phase.

[0086] 3) The second combined organic phase was dried over anhydrous sodium sulfate to remove water, concentrated under reduced pressure, and purified by column chromatography using petroleum ether to ethyl acetate in a volume ratio of 10:1 to obtain 295 mg of the third compound, with a calculated yield of 85%. The third compound was analyzed using a Bruker AVANCE 600 spectrometer with nuclear magnetic resonance (NMR). The 1H NMR spectrum is shown below. Figure 2 , 1 The H NMR results are as follows: (300 MHz, CDCl3) 8.57 (d, J = 15.7 Hz, 1H, NH),8.50 – 8.41 (m, 2H, Ph-H), 8.20 (m, 1H, Ph-H), 7.77 (m, 2H, Ph-H), 7.58 –7.49 (m, 1H, Ph-H), 7.38 – 7.28 (m, 1H, Ph-H), 7.20 (m, 1H, Ph-H), 6.88 (s,1H, pyrimidin-H), 2.53 (s, 3H, CH3), 2.02 – 1.92 (m, 1H, CH), 1.28 – 1.22 (m,2H, CH2), 1.11 – 1.03 (m, 2H, CH2); HRMS (ESI) calcd for C 21 H 19 FN3O (M+H + )348.1512, found 348.1498. The results showed that the third compound was N-(4-(4-cyclopropyl-6-methylpyrimidin-2-yl)phenyl)-2-fluorobenzamide, which was designated as PPI-A3.

[0087] In this embodiment, 2-fluorobenzoic acid was replaced with the substituted acid listed in Table 2, and other operations were the same as in this embodiment, to synthesize PPI-A1, PPI-A3 to PPI-A12. The compound numbers, substituted acids used in the reaction, substituents corresponding to R1, physicochemical data, and appearance are shown in Table 2. The proton NMR and high-resolution mass spectrometry data for structural identification are shown in Table 3. Example 3: Preparation and structural identification of compound PPI-A13

[0088]

[0089] 1) PPI-A0 (113 mg, 0.5 mmol), chloroacetic acid (56.7 mg, 0.6 mmol), 2-(7-azobenzotriazole)-tetramethylurea hexafluorophosphate (HATU, 228 mg, 0.6 mmol), triethylamine (138 μL, 1 mmol) and anhydrous dichloromethane (5 mL) were added to a flask. The mixture was stirred at room temperature for 10 hours under a nitrogen atmosphere. The reaction was confirmed to be complete by thin-layer chromatography using petroleum ether and ethyl acetate in a volume ratio of 3:1 as the developing solvent. The reaction was quenched with 20 mL of water to obtain the fourth reactant.

[0090] 2) Extract the fourth reactant twice with 20 mL of dichloromethane each time, and combine the organic phases extracted twice to obtain the third combined organic phase.

[0091] 3) The third combined organic phase was dried over anhydrous sodium sulfate to remove water, concentrated under reduced pressure, and purified by column chromatography using petroleum ether to ethyl acetate (volume ratio 15:1) as the mobile phase to obtain 132 mg of the fourth compound. The yield was calculated to be 87%. The fourth compound was detected using a Bruker AVANCE 600 spectrometer with nuclear magnetic resonance (NMR). 1 The 1H NMR results are as follows: (300 MHz, CDCl3) δ 8.54 – 8.40 (m, 2H, Ph-H), 8.33 (s, 1H, NH), 7.72 – 7.59 (m, 2H, Ph-H), 6.89 (s, 1H, pyrimidin-H), 4.21 (s, 2H, CH2), 2.50 (s, 3H, CH3), 1.99 – 1.77 (m, 1H, CH), 1.31 – 1.17 (m, 2H, CH2), 1.11 – 0.97 (m, 2H, CH2). HRMS (ESI) calcd for C 21 H 20 N3O (M+H + ) 302.1060, found 302.1051. The results showed that the fourth compound was 2-chloro-N-[4-(4-cyclopropyl-6-methylpyrimidin-2-yl)phenyl]acetamide, which was designated PPI-A13.

[0092] Table 2

[0093] Table 3 Example 4: Antibacterial activity test

[0094] Compounds PPI-A0 to PPI-A13 and benzalkonium chloride were prepared into 10 mg / mL solutions using dimethyl sulfoxide.

[0095] Each pathogen to be tested was inoculated onto PDA medium and incubated at 25°C for 2 days. After perforating with a 7mm diameter punch, the medium was then inoculated onto PDA plates containing a final concentration of each compound of 50 μg / mL. PDA plates containing neither the compound nor dimethyl sulfoxide served as a blank control group. One plate constituted one biological replicate, with three replicates. The plates were incubated at 25°C. After the pathogens in the blank control group had grown sufficiently, the diameter (mm) of colonies in each plate was measured using the cross-hatching method. The average value was taken, and the inhibition rate was calculated. The inhibition rate results are shown in Table 4.

[0096] Antibacterial rate (%) = (colon diameter of blank control group - colony diameter of each compound treatment group) × 100 / (colon diameter of blank control group - 7).

[0097] Table 4

[0098] As shown in Table 4, the compounds PPI-A0 to PPI-A13 of the present invention have antibacterial activity against Fusarium graminearum, black rot of apple, Sclerotinia sclerotiorum and Staphylococcus aureus. Example 5: Formulation of emulsifiable concentrates of compounds PPI-A0 to PPI-A13

[0099] Add 1 to 10 g of compound PPI-A3, 5 to 15 g of emulsifier (Tween-60), and 0.1 to 1 g of penetrant (JFC-2) to a 100 mL volumetric flask, and then dilute to volume with a solvent such as xylene to obtain an emulsifiable concentrate with a content of 1% to 10%.

[0100] The emulsifiable concentrates of PPI-A0 to PPI-A2 and PPI-A4 to PPI-A13 compounds were prepared according to the above method. Example 6: Formulation of wettable powders of compounds PPI-A0 to PPI-A13

[0101] Take 15 to 50 g of compound PPI-A3, 10 to 20 g of surfactant SP408, and 30 to 75 g of silica, mix and pulverize them to obtain a wettable powder with a content of 15% to 50%.

[0102] The wettable powders of compounds PPI-A0 to PPI-A2 and PPI-A4 to PPI-A13 were all prepared according to the above method.

Claims

1. A pyrimidine compound or a pesticide-acceptable salt thereof, having the chemical structural formula shown in Formula I), Equation I), in, R is selected from H or R1CO; R1 is selected from alkyl, haloalkyl, phenyl and substituted phenyl.

2. The compound according to claim 1, characterized in that, The alkyl group is one of C1 to C4 alkyl groups; and / or The halogen group is selected from one of fluorinated, chloro, and bromo groups; and / or The substituted phenyl group is selected from at least one of alkylphenyl, halophenyl, nitrophenyl, alkoxyphenyl and haloalkylphenyl.

3. The compound according to claim 1, characterized in that, R1 is selected from at least one of chloromethyl, phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-bromophenyl, 4-bromophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-methylphenyl, 4-trifluoromethylphenyl, and 4-methoxyphenyl.

4. The method for preparing the compound according to claim 1, comprising first reacting 2-chloropyrimidine with 4-nitrophenylboronic acid to generate 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine, and then reducing 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine to generate the compound in claim 1 where R is H.

5. The method for preparing the compound according to any one of claims 1 to 3, wherein a compound in which R is H in the compound according to claim 1 is reacted with a substituted acid in the presence of a condensing agent to generate a compound in which R is R1CO in the compound according to any one of claims 1 to 3; Preferably, the substituted acid is selected from one of alkyl acids, haloalkyl acids, benzoic acid, and substituted benzoic acid; Preferably, the substituted acid is selected from one of benzoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, 3-chlorobenzoic acid, 4-chlorobenzoic acid, 3-bromobenzoic acid, 4-bromobenzoic acid, 3-nitrobenzoic acid, 4-nitrobenzoic acid, 4-methylbenzoic acid, 4-trifluoromethylbenzoic acid, 4-methoxybenzoic acid, and 2-chloroacetic acid.

6. The preparation method according to claim 4, characterized in that, The preparation method includes the following steps: 1) 2-chloropyrimidine, 4-nitrophenylboronic acid, a first palladium catalyst and a first solvent are mixed and reacted under a first alkaline condition and a first inert gas atmosphere at a first temperature for a first duration to obtain a first reactant containing 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine; 2) The 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine was isolated and purified from the first reactant; 3) The 4-cyclopropyl-6-methyl-2-(4-nitrophenyl)pyrimidine, the second palladium catalyst, and the second solvent are mixed and reacted at a second temperature for a second duration under a hydrogen atmosphere to obtain a second reactant containing a compound in which R is H in the compound as described in claim 1; 4) The compound in which R is H in claim 1 is isolated and purified from the second reactant.

7. The preparation method according to claim 5, characterized in that, The preparation method includes the following steps: I) The compound in claim 1 in which R is H, the substituted acid, the condensing agent and the third solvent are mixed and reacted under a second alkaline condition and a second inert gas atmosphere at a third temperature for a third duration to obtain a third reactant containing a compound in any one of claims 1 to 3 in which R is R1CO. II) Separate and purify from the third reactant the compound in which R is R1CO as described in any one of claims 1 to 3.

8. The preparation method according to claim 6 or 7, characterized in that, The first palladium catalyst is selected from at least one of tetra(triphenylphosphine)palladium, palladium chloride, and 1,1'-bis(diphenylphosphine)ferrocene palladium dichloride, and / or The second palladium catalyst is selected from palladium hydroxide on carbon and palladium on carbon; and / or The condensing agent is selected from one of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 2-(7-azobenzotriazole)-tetramethylurea hexafluorophosphate, N,N-dicyclohexylcarbodiimide, and N,N'-diisopropylcarbodiimide; and / or The first solvent is a mixture of water and ethanol; and / or The second solvent is tetrahydrofuran and / or chloroform; and / or The third solvent is dichloromethane and / or N,N-dimethylformamide; and / or The first alkaline condition is adjusted by at least one of sodium hydroxide, cesium carbonate, sodium bicarbonate, sodium acetate, sodium carbonate, potassium carbonate, and potassium acetate; and / or The second alkaline condition is adjusted by triethylamine and / or diisopropylethylamine; and / or The first inert gas is nitrogen; and / or The second inert gas is nitrogen; and / or The first temperature is -20 to 100 degrees Celsius; and / or The second temperature is 0 to 80 degrees Celsius; and / or The third temperature is -20 to 50 degrees Celsius; and / or The first duration is 1 to 20 hours; and / or The second duration is 0.5 to 10 hours; and / or The third duration is 1 to 20 hours; Preferably, the first temperature is 80 to 100 degrees Celsius; and / or The second temperature is 5 to 40 degrees Celsius; and / or The third temperature is 5 to 40 degrees Celsius; and / or The first duration is 8 to 12 hours; and / or The second duration is 1 to 5 hours; and / or The third duration is 8 to 12 hours.

9. A composition comprising a compound according to any one of claims 1 to 3 or a compound prepared by any one of claims 4 to 8, and an adjuvant that is pesticide-acceptable; Preferably, the composition is a bactericide emulsifiable concentrate or a bactericide wettable powder.

10. The use of the compound according to any one of claims 1 to 3, the compound prepared by the method according to any one of claims 4 to 8, or the composition according to claim 9 in the inhibition of plant pathogenic fungi; Preferably, the plant pathogenic fungus is Fusarium graminearum (Fusarium graminearum). Fusarium graminearum ), Apple black rot fungus ( Valsa mali ), Sclerotinia sclerotiorum ( Sclerotinia sclerotiorum ) and Staphylococcus aureus ( Botryosphaeria dothidea At least one of the following.

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