CN117126147A - Pyrimidine substituted 1,3, 4-oxadiazole derivative, preparation method and application - Google Patents

Pyrimidine substituted 1,3, 4-oxadiazole derivative, preparation method and application Download PDF

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CN117126147A
CN117126147A CN202311018396.8A CN202311018396A CN117126147A CN 117126147 A CN117126147 A CN 117126147A CN 202311018396 A CN202311018396 A CN 202311018396A CN 117126147 A CN117126147 A CN 117126147A
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methyl
chlorophenyl
hydrogen
pyrimidine
cyanophenyl
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吴文能
潘年娟
安建松
费强
陈海江
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Guiyang University
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Guiyang University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention discloses pyrimidine substituted 1,3, 4-oxadiazole derivatives, which have a structure expressed by the following general formula:

Description

Pyrimidine substituted 1,3, 4-oxadiazole derivative, preparation method and application
Technical Field
The invention relates to the technical field of pesticide synthesis, in particular to a pyrimidine substituted 1,3, 4-oxadiazole derivative, a preparation method and application thereof in resisting plant pathogenic bacteria and TMV viruses.
Background
Pyrimidine is an important nitrogenous heterocyclic compound and is an active structural unit in many medicaments, and the pyrimidine compound is concerned by pharmacists because of the characteristics of high efficiency, low toxicity, multiple pharmacological activities, multidirectional transformation of ring substituents and the like. Pyrimidine is not only a vital substance unit in life activities, such as the 3 pyrimidine structures of nucleic acids, namely uracil, cytosine and thymine; also has wide biological activity, such as antivirus, anti-tumor, antibiosis, disinsection, weeding, etc., and has been widely used in the fields of medicine and pesticide.
The 1,3, 4-oxadiazole ring is a five-membered aromatic heterocycle containing two nitrogen atoms, the molecule contains two nitrogen atoms and a pi-pi conjugated system, the compound has stronger capability of complexing metal ions and forming hydrogen bonds, and the unique structural property enables the oxadiazole compound to show broad-spectrum biological activity, such as insecticidal activity, bactericidal activity, weeding activity, anticonvulsant activity, anticancer activity and the like. Oxadiazole compounds of different structures tend to have different biological activities.
The foregoing is provided merely for the purpose of facilitating understanding of the technical solutions of the present invention and is not intended to represent an admission that the foregoing is prior art.
Disclosure of Invention
The invention aims to provide pyrimidine substituted 1,3, 4-oxadiazole derivatives and a preparation method thereof, and a series of medicaments for resisting plant pathogenic bacteria, plant disease bacteria and viruses are synthesized by utilizing the derivatives.
In order to achieve the above object, the technical scheme of the present invention is as follows:
pyrimidine substituted 1,3, 4-oxadiazole derivatives have the structure expressed by the following general formula:
wherein R1 is hydrogen or methyl; r2 is hydrogen, methyl, 2-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 4-fluorophenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2, 4-dichlorophenyl, 3, 4-dichlorophenyl, 2-cyanophenyl, 4-cyanophenyl.
The invention also provides a preparation method of the pyrimidine substituted 1,3, 4-oxadiazole derivative, which comprises the following steps:
wherein, R1 is hydrogen or methyl; r2 is hydrogen, methyl, 2-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-trifluoromethylphenyl, 2, 4-dichlorophenyl, 3, 4-dichlorophenyl, 2-cyanophenyl, 4-cyanophenyl.
The pyrimidine substituted 1,3, 4-oxadiazole derivative can be applied to preparation of plant pathogen or virus resistant medicines.
Detailed Description
It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1: pyrimidine substituted 1,3, 4-oxadiazole derivatives have the following structural general formula:
wherein R1 is hydrogen or methyl; r2 is hydrogen, methyl, 2-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 4-fluorophenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2, 4-dichlorophenyl, 3, 4-dichlorophenyl, 2-cyanophenyl, 4-cyanophenyl.
The preparation method comprises the following steps:
s1, using ethyl trifluoroacetoacetate and formamidine hydrochloride or acetamidine hydrochloride as raw materials, and absolute ethyl alcohol (CH) 3 CH 2 OH) is used as a solvent, DBU is used as an acid binding agent, and intermediate 1 (4-hydroxy-6-trifluoromethyl pyrimidine or 2-methyl-4-hydroxy-6-trifluoromethyl pyrimidine) is prepared by reflux.
The specific reaction formula is as follows:
wherein R is 1 Is hydrogen or methyl.
The specific operation procedure of step S1 is described below (those skilled in the art may also adopt other operation procedures according to the above reaction formula):
to a 100mL round bottom flask was added 50mmol of ethyl trifluoroacetoacetate and 80mmol of formamidine hydrochloride or acetamidine hydrochloride, followed by addition of DBU 50mmol, refluxing with absolute ethyl alcohol for 10h, vacuum drying the solvent, then adding 20mL of pure water, extracting with ethyl acetate, drying under reduced pressure, concentrating, washing with dichloromethane to obtain intermediate 1, yield: 75.8%.
The person skilled in the art can also change the solvent and the acid-binding agent in this example.
S2, taking the intermediate 1 as a raw material, N, N-diisopropylethylamine as a catalyst, acetonitrile as a solvent, and performing POCl (point of care testing) on the mixture 3 The intermediate 2 (4-chloro-6-trifluoromethyl pyrimidine or 2-methyl-4-chloro-6-trifluoromethyl pyrimidine) is prepared under the condition of a chlorinating reagent.
The specific reaction formula is as follows:
wherein R is 1 Is hydrogen or methyl.
The specific operation procedure of step S2 is described below (those skilled in the art may also adopt other operation procedures according to the above reaction formula):
40mmol of intermediate 1, 30mmol of N, N-diisopropylethylamine and 40mL of acetonitrile were sequentially added to a 100mL three-necked flask, and stirred for 5 minutes, followed by 60 mmole POCl 3 After diluting with acetonitrile, slowly dropping in a flask under ice bath condition, heating and refluxing for 5 hours, drying the solvent under reduced pressure, adding 20mL of ice water into the system, and using NaHCO 3 Adjusting the pH to about 9, extracting with dichloromethane for 3 times, and drying under reduced pressure to obtain a tan liquid, namely the intermediate 2.
The solvent, catalyst and chlorinating agent in this example can also be replaced by those skilled in the art.
S3, taking the intermediate 2 as a raw material, taking cesium carbonate as a catalyst, taking acetone as a solvent, and reacting with methyl p-hydroxybenzoate to prepare intermediate 3 (methyl 4- ((2-methyl-6- (trifluoromethyl) pyrimidin-4-yl) oxy) benzoate or methyl 2-methyl-4- ((2-methyl-6- (trifluoromethyl) pyrimidin-4-yl) oxy) benzoate.
The specific reaction formula is as follows:
wherein R is 1 Is hydrogen or methyl.
The specific operation procedure of step S3 is described below (those skilled in the art may also adopt other operation procedures according to the above reaction formula):
0.01mol of intermediate 2, 0.012mol of 4-hydroxybenzoic acid ethyl ester, 0.02mol of cesium carbonate and 40mL of acetone are sequentially added into a 100mL three-neck flask, the reaction is carried out for 2 to 4 hours at normal temperature, after the reaction is finished, the solvent is dried under reduced pressure at 40 ℃, and the solid is obtained after ethanol recrystallization, namely the intermediate 3.
The solvent and catalyst in this example can also be replaced by those skilled in the art.
S4, reacting the intermediate 3 serving as a raw material with 80% hydrazine hydrate serving as a hydrazinolysis reagent in a methanol solvent to prepare an intermediate 4 (4- ((2-methyl-6- (trifluoromethyl) pyrimidine-4-yl) oxy) benzoyl hydrazine or 4- ((6- (trifluoromethyl) pyrimidine-4-yl) oxy) benzoyl hydrazine).
The specific reaction formula is as follows:
wherein R1 is hydrogen or methyl.
The specific operation procedure of step S4 is described below (those skilled in the art may also adopt other operation procedures according to the above reaction formula):
20mmol of intermediate 3 is added into a 100mL three-neck flask, 40mL of methanol is added for dissolution, 60mmol of 80% hydrazine hydrate is slowly added dropwise, after the reaction is heated and refluxed for 5-7h, the reaction system is cooled to room temperature, the precipitated solid is filtered, and the solid is obtained through ethanol recrystallization, namely intermediate 4.
The person skilled in the art can also change the solvents and hydrazolytic reagents in this example.
S5, reacting the intermediate 4 serving as a raw material with carbon disulfide under an alkaline condition of a KOH aqueous solution by using ethanol as a solvent to obtain an intermediate 5 (5- (4- ((2-methyl-6- (trifluoromethyl) pyrimidin-4-yl) oxy) phenyl) -1,3, 4-oxadiazole-2-thiol or 5- (4- ((6- (trifluoromethyl) pyrimidin-4-yl) oxy) phenyl) -1,3, 4-oxadiazole-2-thiol).
The specific reaction formula is as follows:
wherein R1 is hydrogen or methyl.
The specific operation procedure of step S5 is described below (those skilled in the art may also adopt other operation procedures according to the above reaction formula):
30mmol of intermediate 4, 45mmol of KOH and 50mL of ethanol are sequentially added into a 100mL three-necked flask, and 36mmol of CS is slowly added dropwise after the solid is dissolved 2 After heating reflux reaction for 8 hours at 85 ℃, cooling the reaction system to room temperature, filtering to precipitate solid, washing with pure water for 2-3 times, and recrystallizing with ethanol to obtain solid, namely intermediate 5.
The person skilled in the art can also change the solvents and alkaline reagents in this example.
S6, taking the intermediate 5 as a raw material, and mixing with ClCH under the alkaline condition of NaOH aqueous solution 2 R 2 The reaction is carried out to prepare a series of pyrimidine substituted 1,3, 4-oxadiazole derivatives (target compound 6).
The specific reaction formula is as follows:
wherein R1 is hydrogen or methyl; r2 is hydrogen, methyl, 2-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-trifluoromethylphenyl, 2, 4-dichlorophenyl, 3, 4-dichlorophenyl, 2-cyanophenyl, 4-cyanophenyl.
The specific operation procedure of step S6 is described below (those skilled in the art may also adopt other operation procedures according to the above reaction formula):
in a 50mL single vial, 2mmol of intermediate 5, 2mmol of ClCH 2 R 2 And 2.2mmol of NaOH is dissolved in 15mL of water, stirred at room temperature for reaction for 2-4h, after the reaction is completed, the solid is filtered, and pure solid is obtained through ethanol recrystallization, namely the target compounds 6a-6y.
The alkaline reagent in this example can also be replaced by a person skilled in the art.
This example provides 25 specific reactant combinations to yield 25 target compounds 6 (6 a-6 y), as shown in Table 1 below:
TABLE 1
Physicochemical properties and high-resolution mass spectrum data of the synthesized pyrimidine substituted 1,3, 4-oxadiazole derivative are shown in table 2.
TABLE 2
Nuclear magnetic resonance hydrogen spectrum of pyrimidine substituted 1,3, 4-oxadiazole derivative 1 H NMR) and carbon spectrum [ ] 13 C NMR) data are shown in table 3.
TABLE 3 Table 3
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Example 2: test of the activity against phytopathogenic fungi of pyrimidine-substituted 1,3, 4-oxadiazole derivatives:
(1) Test method
The in vitro activity evaluation of 9 plant pathogenic fungi including Botrytis cinerea (B.dothidea), phomopsis sp, blueberry gray mold (B.cinerea), cucumber gray mold, rape sclerotium, tobacco gray mold, strawberry gray mold, anthracnose and rice blast is carried out by adopting a hypha growth rate method, and the commercial medicament pyrimethanil is used as a positive control. The method comprises the following specific steps:
PDA medium: 200g of potato, 10g of glucose, 15g of agar and 1L of ultrapure water were measured. Removing potato skin, cutting into small pieces, weighing 200g, decocting in 800mL ultrapure water until the potato skin can be broken by stamping with a glass rod, filtering with double-layer gauze, and removing residue. Weighing 10g of glucose and 15g of agar, respectively adding into the filtrate, boiling, continuously stirring by using a glass rod during the boiling to ensure that the glucose and the agar are uniformly dissolved in the potato solution, adding ultrapure water to a volume of 1L, weighing 95mL into a 150mL conical flask, sealing the bottle mouth of the conical flask by using a semipermeable membrane, and placing the conical flask into a sterilizing pot for sterilizing for 20min at 121 ℃.
Inoculating: 0.005g of the target compound was weighed and dissolved by adding 1000mL of DMSO, then 4mL of sterile water was added, and after mixing well, poured into 95mL of medium and into 9 dishes on average, and cooled for use. The test strain was activated in advance. In a sterile operation table, a sterilized 5mm puncher is used for punching a test strain activated in advance into single bacterial cakes, forceps are used for taking the bacterial cakes after forceps are sterilized, the bacterial cakes are reversely buckled in the center of a drug-containing culture medium, one bacterial cake is placed in each culture medium, a blank culture medium of DMSO is used as a negative control, and pyrimethanil with the concentration of 50 mug/mL is used as a positive control for experiments. After all the culture mediums are inoculated, sealing the culture dish with a sealing film, and culturing in a constant temperature incubator at 28 ℃ for 2-5 days. Colony diameter was measured according to the crisscross method when the hyphal growth of the colonies of the negative control group occupied 3/4 of the whole dish. 3 replicates were set for each treatment, 3 replicates for each trial. The bacteriostasis rate was calculated according to the following formula:
I(％)＝(C tur -T tur )/(C tur -0.5)×100；
wherein C is tur Colony diameter for negative control; t (T) tur Colony diameter for the agent treatment group; 0.5 is the diameter of the fungus cake; i is the inhibition rate.
(2) The results of the biological activity test against plant pathogenic fungi are shown in tables 4-1 and 4-2:
TABLE 4-1
Remarks: average three replicates; pyrimethanil (Pyrimethanil) was used as a positive control.
TABLE 4-2
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Remarks: average three replicates; pyrimethanil (Pyrimethanil) was used as a positive control.
Experimental results show that part of the compounds have better biological activity on the tested strain. Wherein the antibacterial rate of 3 compounds to the botrytis cinerea blueberry reaches 100%, the antibacterial rate of 1 compound to the botrytis cinerea strawberry reaches 100%, and the antibacterial rate of 4 compounds to the phomopsis is more than 80%. In view of the high antibacterial activity of the series of compounds, EC is prepared for the blueberry ash mold, the strawberry ash mold and the phomopsis mold 50 And (5) testing.
The obtained total 25 target products, wherein the antibacterial rate of the compounds 6c, 6g and 6s on B.cinerea is 100 percent. The bacteriostasis rate of 6g, 6s, 6u and 6x to Phomopsis sp.
According to the experimental result, part of target compounds are subjected to EC on Botrytis cinerea, botrytis cinerea and Botrytis cinerea 50 The values were determined and the results are shown in Table 5.
Wherein, the target compounds 6c, 6g and 6s have better antibacterial activity on the blueberry gray mold, and EC 50 The values were 8.12. Mu.g/mL, 14.36. Mu.g/mL and 5.18. Mu.g/mL, respectively. Pyrimethanil (EC) 50 =62.8 μg/mL); the compounds 6g, 6s, 6u and 6x show better antibacterial activity on phomopsis, and EC 50 Values were 20.07. Mu.g/mL, 14.56. Mu.g/mL, 29.34 and 19.32. Mu.g/mL, respectively; the compounds 6b, 6f and 6j have better antibacterial activity on the gray mold of the strawberry, and EC 50 The values were 15.09. Mu.g/mL, 8.50. Mu.g/mL and 15.89. Mu.g/mL, respectively, 6f and the control drug pyrimethanil (EC 50 =25.68 μg/mL) activity was comparable.
TABLE 5
From the table, the compounds show good inhibitory activity on the tested strain, wherein the compounds 6b, 6f and 6j have better inhibitory effect on the blueberry ash mold, and the inhibitory activity of the three compounds is better than that of the control drug pyrimethanil.
Example 3: assay of anti-tobacco mosaic virus TMV activity of pyrimidine-substituted 1,3, 4-oxadiazole derivatives:
(1) Test method
Protection of TMV by agents:
the leaf tobacco with consistent growth vigor is selected, and the solvent with the dosage corresponding to the left half She Tushi medicament and the right half She Tushi medicament is gently used as a control. Performing wet culture in illumination incubator at 23+ -1deg.C for 12 hr under 10000Lux, inoculating virus, and dipping with writing brush to give a concentration of 6X10 -3 mg/mL virus juice is manually rubbed and inoculated on the leaf blade scattered with silicon carbide, and the leaf surface (whole leaf) is lightly rubbed for 1-2 times along the branch pulse direction. The underside of the leaf is supported by palm or layers of filter paper. And washing the inoculated leaves with clear water after inoculation. Then, the culture was kept under humidity in an illumination incubator at a temperature of 23.+ -. 1 ℃ for 10000Lux 3-4d, and the number of generated dried spots was observed and recorded. 3 plants, 3-4 leaves per plant, were set per drug treatment. Each agent was repeated 3 times as described above.
In vivo inactivation of TMV by agents:
selecting leaf tobacco with consistent growth vigor, diluting TMV to 6×10-3mg/mL with phosphoric acid buffer solution, mixing the medicament with the virus juice with equal volume, inactivating for 30min, manually rubbing with a writing brush to inoculate the left half leaf of the leaf tobacco with proper age, and mixing the solvent with the virus juice with corresponding dosage to inoculate the right half leaf; after inoculation, the seeds are rinsed with clear water. Subsequently, the culture was kept under humidity in an illumination incubator at a temperature of 23.+ -. 1 ℃ for 10000Lux under illumination for 3-4d, and the number of generated spots was observed and recorded. 3 plants, 3-4 leaves per plant, were set per drug treatment. Each agent was repeated 3 times as described above.
In vivo therapeutic effects of agents on TMV infection:
selecting a leaf tobacco with consistent growth vigor, dipping a writing brush in virus juice, inoculating the virus to the whole leaf, and flushing with clear water after inoculation. After the leaves were dried, the corresponding dose of solvent was used as a control in the left half She Tushi of the dose and the right half She Tushi. Subsequently, the culture was kept under humidity in an illumination incubator at a temperature of 23.+ -. 1 ℃ for 10000Lux under illumination for 3-4d, and the number of generated spots was observed and recorded. 3 plants, 3-4 leaves per plant, were set per drug treatment. Each agent was repeated 3 times as described above.
The calculation formula is as follows:
when the half leaves of the blank control show obvious dead spots, the investigation can be carried out after about 3-4d, the dead spot numbers of the left and right half leaves of each leaf are respectively recorded, and the inhibition rate of the tested compound on the tobacco mosaic virus, namely the relative effect, is calculated as follows.
Y＝[(C-A)/C]×100％
Wherein: y is the inhibition rate of the compound on tobacco mosaic virus; c is the number of dead spots in the control group (right half leaf): a plurality of; a is the number of dead spots in the control group (left half leaf): and each.
Each treatment was referenced to the other half of the treatment by setting a further set of Ningnanmycin.
The results of the in vivo antiviral activity test of the objective compound against TMV at a concentration of 500. Mu.g/mL are shown in Table 6.
TABLE 6
As can be seen from Table 6, most of the target compounds had a good inhibitory activity against Tobacco Mosaic Virus (TMV) at a concentration of 500. Mu.g/mL. Therapeutically active compounds 6d, 6f and 6r were 58.2%, 58.8% and 61.3%, respectively, slightly better than the control agent ningnanmycin (56.40%); in terms of protective activity, the protective activity of compound 6s was 68.7%, comparable to that of the control agent ningnanmycin (66.4%), and the therapeutic activity of the other compounds on TMV was lower than that of ningnanmycin. In terms of passivating activity, all targets had moderate inhibitory activity, with compound 6t having a passivating activity of 80.0% respectively, slightly lower than that of ningnanmycin (94.0%), and other compounds lower than that of the control agent ningnanmycin.
EC of partial Compounds to TMV 50 The test results are shown in Table 7.
TABLE 7
It can be seen from Table 2 that compounds 6d, 6f and 6r have higher therapeutic activity than Ningnanmycin, its EC 50 Values 295.2, 276.1 and 227.5. Mu.g/mL, respectively, whereas the EC of Ningnanmycin 50 Is 301.8. Mu.g/mL. EC of Compound 6x to TMV protection 50 203.4 mug/mL, is also higher than Ningnanmycin activity.
The activity test is carried out on the obtained target compound, and the experimental result shows that pyrimidine substituted 1,3, 4-oxadiazole derivatives have a certain inhibition effect on part of plant pathogens, wherein part of target compounds show better inhibition activity on test pathogens, so that the pyrimidine substituted 1,3, 4-oxadiazole derivatives can be applied to the development of pesticides, in particular to medicaments for resisting plant viruses or pathogens.
The foregoing description of the preferred embodiments of the present invention should not be construed as limiting the scope of the invention, but rather should be construed to cover all equivalent structures or equivalent processes or direct or indirect application to other related arts.

Claims (6)

1. Pyrimidine-substituted 1,3, 4-oxadiazole derivatives, characterized by having a structure expressed by the general formula:
wherein R1 is hydrogen or methyl; r2 is hydrogen, methyl, 2-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 4-fluorophenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2, 4-dichlorophenyl, 3, 4-dichlorophenyl, 2-cyanophenyl, 4-cyanophenyl.
2. Pyrimidine substituted 1,3, 4-oxadiazole derivatives according to claim 1, having the following structural formula:
3. a process for the preparation of pyrimidine substituted 1,3, 4-oxadiazole derivatives according to claim 1, comprising the steps of:
wherein, R1 is hydrogen or methyl; r2 is hydrogen, methyl, 2-methylphenyl, 4-methylphenyl, 2-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-trifluoromethylphenyl, 2, 4-dichlorophenyl, 3, 4-dichlorophenyl, 2-cyanophenyl, 4-cyanophenyl.
4. Use of pyrimidine substituted 1,3, 4-oxadiazole derivatives as claimed in claim 1 in the preparation of anti-plant pathogen or virus drugs.
5. An anti-tobacco mosaic virus drug characterized in that the active ingredient comprises any one of the compounds 6a-6y.
6. The plant pathogen resisting medicine is characterized in that the effective component contains any one of compounds 6a-6y.
CN202311018396.8A 2023-08-11 2023-08-11 Pyrimidine substituted 1,3, 4-oxadiazole derivative, preparation method and application Pending CN117126147A (en)

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