CN107459514B - Chiral piperidine derivative and preparation method and application thereof - Google Patents
Chiral piperidine derivative and preparation method and application thereof Download PDFInfo
- Publication number
- CN107459514B CN107459514B CN201610402572.1A CN201610402572A CN107459514B CN 107459514 B CN107459514 B CN 107459514B CN 201610402572 A CN201610402572 A CN 201610402572A CN 107459514 B CN107459514 B CN 107459514B
- Authority
- CN
- China
- Prior art keywords
- zyj05
- compound
- activity
- compounds
- chiral
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- 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
- A01N43/74—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 one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
The invention provides a chiral piperidine heterocyclic compound containing N and S, a preparation method and application thereof, and in particular relates to a chiral thiazole piperidine compound which has a chemical structural general formula shown as I.
Description
Technical Field
The technical scheme of the invention relates to a chiral piperidine heterocyclic compound containing N and S, in particular to a chiral thiazole piperidine compound.
Background
The nitrogen-containing heterocyclic compound generally has unique biological activity, low toxicity and high systemic property and is an active structural unit of medicines and pesticides; the nitrogen-containing heterocyclic compound is easy to carry out structural modification, and various functional groups can be conveniently introduced (Zhang in, et al. research progress of the nitrogen-containing heterocyclic compound. petrochemical industry, 2011, 40 (6): 1000-. The thiazole ring is an important five-membered aromatic heterocycle containing nitrogen and sulfur heteroatoms, and the special structure of the thiazole ring ensures that the thiazole compound has wide application prospect in various fields such as chemistry, pharmacy, biology, material science and the like, and shows huge development value (catalytic peak, and the like. new progress of application research of the thiazole compound. China science, 2012, 42 (8): 1105-1131). Piperidine derivatives have a wide range of biological activities, and piperidine alkaloids are widely distributed in the plant kingdom and show a variety of biological activities (Riccherson, G.B., et al, Dnaymai acquilubirium of neuro-ransistors not just for reup-takeano. J.Neurophynol, 2003, 90: 1363-. Piperidine derivatives also exhibit a wide range of biological activities in the field of pesticides, such as the fungicides fenpropidin, the herbicides pipindoside, the plant growth regulators mepiquat chloride, etc. (Jiang, et al, design, synthesis and antibacterial activity of novel triazine derivatives stabilizing sub-stances 1, 2, 3-triazine-piperidine derivatives. eur.j.med.chem, 2014, 82: 490-497). The introduction of the active sub-building block thiazole ring into piperidine compounds has been reported in patents (Black, Janic. novel herbicides, WO2000071900A 1; Pasteris, axial. fungoidal amides, WO2008091580A 2).
The invention introduces thiazole into piperidine compounds containing nitrogen heterocyclic groups by utilizing the principle of pesticide molecular design, designs and synthesizes a new chiral piperidine compound containing thiazole rings, and performs systematic biological activity screening to provide more efficient candidate compounds for the creation of new pesticides.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: provides a synthesis method of novel chiral piperidine derivatives, provides a method for regulating and controlling the biological activity of agricultural, horticultural and sanitary pests and plant pathogens of forestry plants by using the compounds and a determination method thereof, and also provides application of the compounds in the agricultural field, the horticultural field, the forestry field and the sanitary field.
The technical scheme adopted by the invention for solving the technical problem is as follows: the chiral piperidine derivative with insecticidal activity and bactericidal activity in the agricultural field, the horticultural field, the forestry field and the sanitary field has a structural general formula I:
wherein A is selected from propionyl and 1-hydroxypropyl; r1Selected from 2- (4' -tert-butyloxycarbonylpiperidine) thiazol-4-yl, 4-methylthiazol-5-yl, thiazol-4-yl; r2Selected from 4-methoxyphenyl, phenyl, 4-nitrophenyl and cyclopropyl.
The synthesis method of the chiral piperidine derivative I comprises the following steps:
wherein: a is selected from propionyl and 1-hydroxypropyl; r1Selected from 2- (4' -tert-butyloxycarbonylpiperidine) thiazol-4-yl, 4-methylthiazol-5-yl, thiazol-4-yl; r2Selected from 4-methoxyphenyl, phenyl, 4-nitrophenyl, cyclopropyl; TFA is trifluoroacetic acid;
the method comprises the following steps:
A. preparation of intermediate 2, 3, 4, 5-tetrahydropyridinimine III:
adding a chiral tetrahydropyridine derivative II into a 50 ml round-bottom flask, then adding 2-8 ml of thioanisole, slowly dropwise adding 1-5 ml of trifluoroacetic acid under an ice bath condition, stirring for 15 minutes in the ice bath, removing the ice bath, stirring for 3 hours at room temperature, completely reacting, adjusting the pH to 8-9 with 1 mol/L of sodium hydroxide solution, then extracting with dichloromethane, separating a dichloromethane layer, washing a dichloromethane phase with saturated sodium chloride, drying with anhydrous magnesium sulfate, performing suction filtration, concentrating, removing a solvent under reduced pressure, purifying the residue by using a 200-300-mesh silica gel column chromatography to obtain an intermediate 2, 3, 4, 5-tetrahydropyridine imine III, eluting with petroleum ether and ethyl acetate at 60-90 ℃, wherein the volume ratio is 4: 1-2: 1 according to different products, and the yield is 60-90%; the preparation amount of the intermediate 2, 3, 4, 5-tetrahydropyridine imine III and the volume of a reaction container are enlarged or reduced according to the corresponding proportion.
B. Preparation of chiral piperidine derivative I:
adding 0.24 mmol of intermediate 2, 3, 4, 5-tetrahydropyridinimine III into a 50 ml round-bottom flask, then dropwise adding 2-8 ml of glacial acetic acid, adding sodium cyanoborohydride with the molar quantity being 1-3 times that of the intermediate 2, 3, 4, 5-tetrahydropyridinimine III in batches under the condition of water bath, continuing stirring for 10 minutes under the condition of ice bath after the addition is finished, then removing the ice bath, stirring for 2 hours at room temperature and completely reacting, adjusting the pH value to 9-10 by using 1 mol/L of sodium hydroxide solution, then extracting by using ethyl acetate, separating an ethyl acetate layer, washing an ethyl acetate phase by using saturated sodium chloride, drying anhydrous magnesium sulfate, removing a solvent after suction filtration under reduced pressure, purifying the residue by using 200-300-mesh silica gel column chromatography to obtain a chiral piperidine derivative I, wherein an eluent is dichloromethane and methanol, and according to different products, the volume ratio is 40: 1-20: 1, and the yield is 50-70%; the amount of the chiral piperidine derivative I and the volume of the reaction vessel are enlarged or reduced according to the corresponding proportion.
C. The bactericidal activity of the chiral piperidine derivative I of the invention is determined as follows:
the bactericidal or bacteriostatic activity of the chiral piperidine derivative I adopts a thallus growth rate measuring method, and the specific steps are as follows: dissolving 1.8 mg of sample in 2 drops of dimethylformamide, diluting the sample to 500 micrograms/ml of medicament with an aqueous solution containing a certain amount of Tween 20 emulsifier, sucking 1 ml of the reagent to be tested in a culture dish under an aseptic condition, adding 9 ml of PDA culture medium respectively, shaking uniformly to prepare a 50 micrograms/ml medicament-containing flat plate, taking the flat plate added with 1 ml of sterile water as a blank control, cutting a bacterial disc by a puncher with the diameter of 4 mm along the outer edge of hypha, moving the bacterial disc to the medicament-containing flat plate to be placed in an equilateral triangle, repeating the treatment for 3 times, placing the culture dish in a constant-temperature culture box at 24 +/-1 ℃ for culturing, investigating the expansion diameter of each treated bacterial disc after the diameter of the control bacterial colony is expanded to 2-3 cm, calculating the average value, comparing with the blank control to calculate the relative bacteriostasis rate, wherein the test bacterial strain is the species of most of typical plant pathogenic bacteria actually generated in the field in agricultural production in China, the code numbers and names are as follows: AS: tomato early blight, its latin name is: alternaria solani, BC: the cucumber botrytis cinerea with the latin name as follows: botrysticaine, CA: peanut brown spot pathogen, its latin name is: cercospora arachidicola, GZ: wheat scab, its latin name is: gibberella zeae, PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de Bary, PP: apple ring rot, its latin name is: physiosporia piricola, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii, RC: rhizoctonia cerealis, with the latin name: rhizoctoniacephalis, SS: sclerotinia sclerotiorum, its latin name is: sclerotina sclerotiorum.
D. The invention discloses a method for measuring aphid poisoning activity of a chiral piperidine derivative I, which comprises the following steps:
the method for measuring the aphid poisoning activity of the chiral piperidine derivative I adopts an immersion method, broad bean aphids are normal population fed indoors, and Latin is named Aphis Laburni Kaltenbach (ALK); weighing 2.5 mg of a compound to be tested, adding 1 drop of N, N-Dimethylformamide (DMF) dropwise into a beaker, adding 5 ml of acetone, oscillating and dissolving a sample, and adding water with Tween 80 to prepare a solution to be tested with 200 micrograms/ml; cut the confession broad bean plant that has 30 broad bean aphids at least from the basin, dip in each liquid medicine that awaits measuring for 5 seconds, take out and get rid of unnecessary liquid medicine gently, insert and moisturize on the sponge that has been saturated by water, treat that the liquid medicine covers with the glass cover after air-drying naturally, the opening of glass cover upper end is sealed with the gauze and is used the aphid escape, raises the dead situation of inspection aphid in the cultivation room after 72 hours, and the standard is: all the insects which can crawl or stand or six legs can move violently are live insects; the corrected mortality was calculated with clear water as control.
The invention has the beneficial effects that: the chiral piperidine derivative I is subjected to lead optimization, and the synthesized new compound is subjected to screening of insecticidal activity and bacteriostatic activity.
The synthesis, biological activity and application of chiral piperidine derivative I are more specifically illustrated by specific preparation and biological activity determination examples, which are only used for specifically illustrating the invention and not limiting the invention, and especially, the biological activity is only illustrated and not limiting the patent, and the specific embodiments are as follows:
example 1
Preparation of intermediate 2, 3, 4, 5-tetrahydropyridinimine III:
1.68 mmol of chiral tetrahydropyridine derivative II is added to a 50 ml round-bottom flask, then 5 ml of thioanisole is added, 2.5 ml of trifluoroacetic acid is slowly dropped under the ice bath condition, the ice bath is removed after stirring for 15 minutes in the ice bath, the stirring is carried out for 3 hours at room temperature, after the reaction is completed, 1 mol of sodium hydroxide solution is used for adjusting the pH value to 8-9, then extracting with dichloromethane, separating a dichloromethane layer, washing a dichloromethane phase with saturated sodium chloride, drying with anhydrous magnesium sulfate, carrying out suction filtration, concentrating, removing the solvent under reduced pressure, purifying the residue by 200-300-mesh silica gel column chromatography to obtain an intermediate 2, 3, 4, 5-tetrahydropyridinimine III, eluting with petroleum ether and ethyl acetate at 60-90 ℃, according to different products, the volume ratio is 4: 1-2: 1, the yield is 60-90%, and the physical and chemical parameters and the structural parameters are shown in table 1; the preparation amount of the intermediate 2, 3, 4, 5-tetrahydropyridine imine III and the volume of a reaction container are enlarged or reduced according to the corresponding proportion.
Example 2
Preparation of chiral piperidine derivative I:
adding 0.24 mmol of intermediate 2, 3, 4, 5-tetrahydropyridine imine III into a 50 ml round-bottom flask, then dropwise adding 5 ml of glacial acetic acid, adding 0.72 mmol of sodium cyanoborohydride in batches under the condition of water bath, stirring for 10 minutes in ice bath after the addition is finished, removing the ice bath, and stirring for 2 hours at room temperature; after the reaction is completed, 1 mol/L of sodium hydroxide solution is used for adjusting the pH value to be 9-10, then ethyl acetate is used for extraction, an ethyl acetate layer is separated, an ethyl acetate phase is washed by saturated sodium chloride again, anhydrous magnesium sulfate is dried, suction filtration and concentration are carried out, a solvent is removed under reduced pressure, a residue is purified by 200-300-mesh silica gel column chromatography to obtain a chiral piperidine derivative I, an eluant is dichloromethane and methanol, the volume ratio is 40: 1-20: 1 according to different products, the yield is 50-70%, and the physicochemical parameters and the structural parameters are shown in table 1; the amount of the chiral piperidine derivative I and the volume of the reaction vessel are enlarged or reduced according to the corresponding proportion.
Example 3
The antibacterial activity determination result of the chiral piperidine derivative I of the invention is as follows:
the codes and names of the common plant pathogenic fungi tested by the invention are as follows: AS: tomato early blight, its latin name is: alternaria solani, BC: the cucumber botrytis cinerea with the latin name as follows: botrytis cinerea, CA: peanut brown spot pathogen, its latin name is: cercospora arachidicola, GZ: wheat scab, its latin name is: gibberellazeae, PI: the late blight of potato, its latin name is: phytophthora infestans (Mont.) de Bary, PP: apple ring rot, its latin name is: physiosporia piricola, PS: rhizoctonia solani, the Latin name of which is: pellicularia sasakii, RC: rhizoctonia cerealis, with the latin name: rhizoctonia cerealis, SS: sclerotinia sclerotiorum, its latin name is: the strains have good representativeness and can represent the species of most pathogenic bacteria in the field in agricultural production.
It is noteworthy that compounds zyj05-140 of the present invention are described in Zugui Shi, Peiyuan Yu, Teck-Pen Long, and Guofu Zhong, catalysis asymmetry [4+2] association of by and-Rauhut-Currier reaction: similar compounds with the structures closest to the chemical structures of the target compounds of the invention, which are reported in facility entry to high purity furan networked tetrahedrons, Angew. chem. int. Ed.2012, 51, 7825-7829, compounds lfy006-39 are high-activity known compounds reported in patent document WO2008091594, compounds lfy004-47 are high-activity known compounds reported in patent CN104650060A, and for comparing the biological activities of the novel compounds synthesized by the invention, known compounds zyj05-105, lfy 006-006 and lfy004-47 with the chemical structures closest to the target compounds of the invention are synthesized by the invention and compared with the biological activities of the target compounds of the invention.
The results of the bacteria growth rate method are shown in table 2, and table 2 shows that the chiral piperidine derivatives I synthesized by the invention have bactericidal activity of different degrees at 50 micrograms/ml, and most of the chiral piperidine derivatives I have good bactericidal activity. For the tomato early blight bacteria, the inhibitory activity of the compounds zyj05-137, zyj05-131, zyj05-139-4 and zyj05-133-1 is more than 30%, the bactericidal activity of the compounds is higher than that of known compounds zyj05-140, lfy006-39 and lfy004-47 with the chemical structures closest to the target compound of the invention reported in the literature, the activity is more than 10% higher than that of a compound lfy004-47 with the chemical structures closest to the target compound of the invention reported in the literature, and the activity of the compounds zyj05-131 and zyj05-133-1 is more than 10% higher than that of a control compound zyj 05-140; for peanut brown spot pathogen, the inhibitory activity of compounds zyj05-130, zyj05-137, zyj05-131, zyj05-139-4 and zyj05-133-1 is more than 40%, the bactericidal activity of the compounds is higher than that of the compounds zyj05-140, lfy006-39 and lfy004-47 with the chemical structures closest to the target compound of the invention reported in the literature, the bactericidal activity is more than 10% higher than that of the known compounds lfy006-39 and lfy004-47 with the chemical structures closest to the target compound of the invention reported in the literature, wherein the bactericidal activity of the compounds zyj05-130, zyj05-137 and zyj05-131 is higher than 60%, the bactericidal activity is higher than that of the known compounds zyj05-140 with the chemical structures closest to the target compound of the invention reported in the literature and the activity of the compounds zyj05-137 is highest, up to 95.24%; for wheat scab, the inhibition activity of compounds zyj05-130, zyj05-137, zyj05-139-4 and zyj05-133-1 is more than 40%, the bactericidal activity is more than 10% higher than that of known compounds zyj05-140 with the closest chemical structures to the target compound of the invention reported in the literature, wherein the bactericidal activity of compounds zyj05-137 is more than 60%, and the bactericidal activity is more than that of known compounds lfy006-39 and lfy004-47 with the closest chemical structures to the target compound of the invention reported in the literature is more than 10%; for ring rot apple, the inhibiting activity of compounds zyj05-75, zyj05-111, zyj05-131, zyj05-139-3, zyj05-139-4, zyj05-133-1, zyj05-133-2 and zyj05-133-8 is more than 50%, the bactericidal activity is more than 10% higher than that of known compounds zyj05-140 and lfy006-39 with the closest chemical structures to the target compound of the invention reported in the literature, wherein the bactericidal activity of the compounds zyj05-111, zyj05-131, zyj05-139-3, zyj05-139-4 and zyj05-133-1 is more than 60%, the activity of the compounds zyj05-111 is the highest and reaches 78.57%, and the bactericidal activity is more than that of known compounds lfy004-47 with the closest chemical structures to the target compound of the invention reported in the literature; for sclerotinia sclerotiorum, the inhibitory activity of compounds zyj05-111, zyj05-131, zyj05-139-3, zyj05-139-4 and zyj05-133-1 is more than 40%, the bactericidal activity is higher than that of known compounds zyj05-140 with the chemical structures closest to the target compound of the invention reported in the literature, wherein the bactericidal activity of compounds zyj05-131, zyj05-139-4 and zyj05-133-1 is higher than 50%, the activity of compound zyj05-133-1 is highest and reaches 96.15%, and the bactericidal activity is higher than that of known compounds lfy006-39 and lfy004-47 with the chemical structures closest to the target compound of the invention reported in the literature; for botrytis cinerea, the inhibiting activity of compounds zyj05-111, zyj05-137, zyj05-131, zyj05-139-3, zyj05-139-4, zyj05-133-1, zyj05-133-2 and zyj05-138 is more than 50%, the bactericidal activity is more than 10% higher than that of known compounds zyj05-140 and lfy006-39 with the closest chemical structures to the target compounds of the invention reported in the literature, wherein the bactericidal activity of the compounds zyj05-137, zyj05-133-1 and zyj05-133-2 is more than 60%; for potato late blight bacteria, the inhibitory activity of the compounds zyj05-75, zyj05-111, zyj05-131 and zyj05-139-3 is more than 40%, and the bactericidal activity is higher than that of known compounds zyj05-140 with the chemical structures closest to the target compounds reported in the literature, wherein the bactericidal activity of the compounds zyj05-75, zyj05-131 and zyj05-139-3 is higher than 50%; for rhizoctonia cerealis, the inhibitory activity of all tested target compounds is more than 60%, wherein the bactericidal activity of the compounds zyj05-137, zyj05-131 and zyj05-139-3 is more than 70%, and the bactericidal activity is more than 10% higher than that of the known compound zyj05-140 with the closest chemical structure to the target compound of the invention reported in the literature; for rhizoctonia solani, the inhibitory activity of compounds zyj05-111, zyj05-139-4 and zyj05-133-1 is more than 30%, the bactericidal activity is more than 10% higher than that of known compounds zyj05-140 and lfy006-39 with the closest chemical structures to the target compounds of the invention reported in the literature, wherein the activity of compounds zyj05-139-4 and zyj05-133-1 is more than 40%, and the bactericidal activity is more than that of known compounds lfy004-47 with the closest chemical structures to the target compounds of the invention reported in the literature is more than 10%.
The bactericidal activity test result of the chiral piperidine derivative I on the resistant botrytis cinerea mutant is shown in Table 3, and Table 3 shows that T3-10, T1-12, FJ1-10 and BC2 are resistant botrytis cinerea mutants and have good resistance to strobilurin bactericides such as azoxystrobin and kresoxim-methyl, the activity of the compound zyj05-25 of the invention on the resistant botrytis cinerea T3-10 is 100 percent and is higher than that of positive trifloxystrobin with the closest chemical structure by more than 30 percent, the activity to the resistant gray mold fungus T1-12 is 92.06 percent, which is higher than the nearest positive trifloxystrobin of the chemical structure by 5 percent, the activity to the resistant gray mold fungus FJ1-10 is 100 percent, which is higher than the positive trifloxystrobin with the closest chemical structure by more than 40 percent, the activity of the resistant botrytis cinerea BC2 is 93.44%, which is higher than that of the positive trifloxystrobin with the closest chemical structure by more than 10%. zyj05-83 has an activity of 100% against Botrytis cinerea FJ1-10, which is higher than 17% of the positive trifloxystrobin with the closest chemical structure; as can be seen from the above analysis, the compounds zyj05-25 and zyj05-83 of the present invention also have excellent bactericidal activity against the resistant botrytis cinerea mutants, which is higher than that of the positive control strobilurin fungicide.
Example 4
Insecticidal activity of the chiral piperidine derivative I of the present invention:
the results of the determination of the insecticidal activity of the chiral piperidine derivative I are shown in table 4, and table 4 shows: the chiral piperidine derivative I has better insecticidal activity, after the test agent concentration is 100 mg/l and the effect is observed for 72 hours, the chiral piperidine derivative I has better poisoning effect on aphids, the insecticidal activity of compounds zyj05-130, zyj05-111, zyj05-137, zyj05-131, zyj05-139-3, zyj05-139-4, zyj05-133-1, zyj05-133-2 and zyj05-138 is more than 30%, the insecticidal activity of the compounds is higher than that of known compounds zyj05-140 and lfy006-39 with the chemical structures closest to the target compounds of the invention reported in the literature, wherein the insecticidal activity of the compounds zyj05-130, zyj05-137, zyj05-131, zyj05-139-4, zyj05-133-1 and yj05-138 is more than 40%, the insecticidal activity is higher than that of the known compounds zyj05-140 with the chemical structures closest to the target compound reported in the literature, and is more than 10%.
The chiral piperidine derivative I also has good insecticidal activity on pest mites of orthoptera, isoptera, hemiptera, homoptera, thysanoptera, coleoptera, lepidoptera, vein-ptera, diptera, hymenoptera and acarina in agriculture, forestry and gardening.
Example 5
The application of the chiral piperidine derivative I and the pesticide composition in preventing and treating agricultural, forestry and horticultural plant insect pests:
all chiral piperidine derivatives I of the invention are combined with any one or two of commercial insecticides selected from the group consisting of: grunts, acetamiprid, emamectin benzoate, milbemectin, abamectin, spinosad, Beta-cypermethrin, cyhalothrin, cyfluthrin, deltamethrin, fenpropathrin, Beta-cyfluthrin, Lambda-cyhalothrin, permethrin, bifenthrin, permethrin, flumethrin, cyhalothrin, imidacloprid, nitenpyram, imidacloprid, thiacloprid, thiamethoxam, clothianidin, dinotefuran, cotin, dinotefuran, diflubenzuron, chlorbenzuron, tefluazuron, fluazuron, flufenoxuron, pyridinuron, lufenuron, chlorflufenoxuron, bayflurea, novifumuron i.e.e.polyfluorourea, CAS number 121451-02-3, fluxuron, Novaluron i.e.e.e.e.e.e.e.g. Novaluron, Novaluron i.e.e.e.e.g. Noviflumuron i.e.e.e.e.g. Novaluron, Novaluron i.e.e.e.e.e.e. Novaluron, nov, Bay SIR-8514 [1- (4-trifluoromethoxyphenyl) -3- (2-chlorophenyl) -urea ], flufenoxuron, Bistrifluuron, Bistrifluron, furfenozide, tebufenozide, chlorfenapyr, methoxyfenozide, chromafenozide, cyfenozide, dimethoate, dichlorvos, acephate, quinalphos, pyridaphethione, cicada powder, carbaryl, pirimicarb, metolcarb, isoprocarb, cartap, fenobucarb, propafenone, carbosulfan, fenitrothion, bromopropylate, hexythiazox, fenpyroximate, tetrazozine, propargite, diafenthiuron, pymetrozine, spirodiclofen, buterflosil, fentin, buprofezin, monosultap, dimehypo, chlorantraniliprole, flubendiamide, cyantraniliprole, fenpyraclofenamide, pyraclofenapyr, pyraclonil, pyl, pymetrozine, Etoxazole, tebufenpyrad, pyridaben, pyriproxyfen and emamectin; the chiral piperidine derivative I accounts for 1-90% of the insecticidal composition by mass, and the chiral piperidine derivative I and the commercial insecticide are mixed in a ratio of 1% to 99% to 1% by mass; the insecticide composition is processed into a dosage form selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the plant insect pests controlled by the insecticidal composition are selected from: red spider, east Asian planthopper, spruce-car locust, Chinese rice locust, Japanese yellow-back locust, Gryllotalpa Sinicae, Gryllotalpa orientalis, rice thrips, thrips tabaci, thrips oryzae, thrips tritici, aleyrodid fuliginosus, aleyrodids fuliginosus, Empoecia fuliginosus, Sectinopsis melanogaster, big leafhopper, cotton leafhopper, Acronychus cicada, Ceratoda fuliginosus, brown planthopper, Aleuropecurus albus, Laodera saccharina, Adenophora horridis, Mylophaga persicae, Aphis gramineus, Kazu Ipomonensis, Adenophora, Aphis viridis, Aleuropecurus, lytus perus pernicifluke, Adenopsis viridis, Orfly, Ornitus stinkbug, Adenopsis terroris, Adenopsis viridis, Adenopsis terres, Adenopsis, Adenop, Plutella xylostella, carposina niponensis, carposina glycines, carposina niponensis, codling borer, pink moth, striped rice borer, pink borer, yellow rice borer, rice leaf roller, striped rice borer, cotton leaf borer, peach moth, armyworm, prodenia litura, rice snout moth, cotton small bridgehead, beet armyworm, sesamia inferens, cotton bollworm, diamond-back moth, black cutworm, yellow cutworm, pirate moth, gypsy moth, sweet potato hawkmoth, bean hawkmoth, straight-line rice skipper, cryptophysalis grain, orange butterfly, jade belt moth, cabbage butterfly, red butterfly, ramie yellow butterfly, lilyturf beetle, pink beetle, black beetle, yellow beetle, black beetle, Aerugo Liriomys, black tortoise, big Holotrichia parallela, Morgans mulatta, Sinopodophylla, Monochamus aurantiaca, Tapionella cupreum, apes apectis, Calotropis chrysosporium, Phymatopsis fusca, Phyllotreta flava, Phaseolus radiatus, Pipisum piscatum, Pediophora faberi, Zedoariae zea, Pediophora tritici, Ceripomoea flavicans, Choisea virens, Choisea orbiculatula, Chrysocola indica, Ceripomoea filiformis, Choisea infantopus, Ceripomoea gossypii, Paralichia canis, Pholiota indica, Anemophilus, mosquito, fly, Tabanus, Mycoplasma melitensis, Musca griseus, Hygrophysalis oryzae, Bactrocera minata, Cucubis lirioides, Musca griseus, Pholiota indica, Pholiota; the plants controlled by the insecticidal composition are selected from the following plants: rice, wheat, barley, oats, corn, sorghum, sweet potato, cassava, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetable, bamboo shoot, hop, pepper, banana, papaya, orchid, bonsai.
Example 6
The application of the chiral piperidine derivative I and the bactericide composition in preventing and treating agricultural, forestry and horticultural plant diseases comprises the following steps:
all chiral piperidine derivatives I of the invention are combined with any one or two of commercial bactericides to form a bactericidal composition for preventing and treating agricultural and forestry and horticultural plant diseases, wherein the commercial bactericides are selected from: benzothiadiazole, tiadinil, abbreviated as TDL, thiamide, methiazide, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, 4-methyl-1, 2, 3-thiadiazole-5-sodium formate, 4-methyl-1, 2, 3-thiadiazole-5-ethyl formate, DL-beta-aminobutyric acid, isotianil, the english generic name of which is: isotianil, 3, 4-dichloroisothiazole-5-carboxylic acid, 3, 4-dichloroisothiazole-5-sodium formate, 3, 4-dichloroisothiazole-5-ethyl formate, ribavirin, antofine, ningnanmycin or salicylic acid, cymoxanil, thiram, ziram, mancozeb, fosetyl-aluminum, thiophanate-methyl, chlorothalonil, dichlorvos, procymidone, fenpropidin, thiophanate-methyl, metalaxyl-M, flumorph, dimethomorph, metalaxyl-M, benalaxyl-M, diclocyanide, sulfsulfamide, thifluzamide, flutolclofenamide, dielphthalein, cyprodinil, cyhexamid, silthiopham, furametpyr, penthiopyrad, fenpropam, iprodione, trifloxystrobin, dimoxystrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, trifloxystrobin, enestrobin, epoxiconazole, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimenol, triticonazole, bitertanol, thiabendazole, fuberidazole, imazalil, prochloraz, triflumizole, cyazofamid, fenamidone, oxpoconazole, fenpyrad, famoxadone, pyridaben, oxadixyl, thiabendazole, trifloxystrobin, octopirox, fenbuconazole, tridemorph, fenpropimorph, fenpropiconazole, fenpyroxapyroxapyrone, fludioxonil, fenpropiconazole, fenpyroxapyroxapyroxapyroxapyroxad-ethyl, flufen, fludioxonil, fludioxo, Fluazinam, pyribenzoxim, cyprodinil, boscalid, fluopicolide, pyrimethanil, cyprodinil, fluoxamid, mepizone, mepanipyrim, pyrimethanil, fenarimol, fluoropyrimidinol, fenaminosulf, dithianon, oxyquinoline, hydroxyquinoline, propoxymine, phenoxyquinoline, diethofencarb, iprovalicarb, benthiavalicarb, propamocarb, edifenphos, iprobenfos, pyrazofos, tolclofos-methyl, blasticidin, kasugamycin, polyoxin, validamycin, streptomycin, metalaxyl, furalaxyl, benalaxyl, furalamide, fenbutamide, carbendazim, benomyl, thiophanate-methyl, triadimefon, bupirimate, dimeticonol, ethirimol, fenarimol, captan, fenflurazole, vinclozolirtide, flufenapyr, dimethachlon, chlorothalonil, fenozide, isoprothiolane, pyriminostrobilyn, pyriminostrobilurin, pyrimethanil, pyri, Bismerthiazol, quintozene, propineb, fosetyl-aluminum, sulfur, bordeaux mixture, copper sulfate, copper oxychloride, cuprous oxide, copper hydroxide, metrafenone, pencycuron, pyridaben, tetrachlorophthalide, pyroquilon, spiroxamine, tricyclazole, azinam, dodine, iminoctadine, chloronitramine, bentiamine, tolfenpyrad, indolylate, sodium diuron, quinconazole, probenazole, bronopol, iodomethane, metam, fenaminoesters, dazomet, dichloroisopropyl ether, fosthiazate, fosfon, ethoprophos, dichlofenthion, buthion, oxamyl, sulfuryl fluoride, dichloropropylene, dichloroisonicotinic acid, probenazole; the total mass percentage content of the chiral piperidine derivative I in the bactericidal composition is 1% -90%, and the ratio of the chiral piperidine derivative I to the commercial bactericide is 1% to 99% to 1% in mass percentage; the bactericidal composition is processed into a dosage form selected from the group consisting of: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the plant diseases controlled by the bactericidal composition are selected from: rice seedling blight, tomato root rot, potato late blight, tobacco black shank, millet powdery mildew, grape downy mildew, lettuce downy mildew, cucumber anthracnose; the plants suitable for the bactericidal composition are selected from the group consisting of: rice, wheat, barley, oats, corn, sorghum, sweet, potato, woody, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, potherby, bamboo shoots, hops, pepper, banana, papaya, orchid, bonsai.
Example 7
The application of the chiral piperidine derivative I and the plant virus resisting agent in preventing and treating virus diseases of agricultural, forestry and horticultural plants is as follows:
all chiral piperidine derivatives I of the invention are combined with any one or two of commercial antiviral medicaments to form an antiviral composition for preventing and treating viral diseases of agricultural, forestry and horticultural plants, wherein the commercial antiviral medicaments are selected from: diazosulfide and tiadinil, which are abbreviated as TDL and isotianil, and have English common names of: isotianil, 4-methyl-1, 2, 3-thiadiazole-5-carboxylic acid, 4-methyl-1, 2, 3-thiadiazole-5-sodium formate, 4-methyl-1, 2, 3-thiadiazole-5-ethyl formate, 3, 4-dichloroisothiazole-5-carboxylic acid, 3, 4-dichloroisothiazole-5-sodium formate, 3, 4-dichloroisothiazole-5-ethyl formate, DL-beta-aminobutyric acid, ribavirin, antofine, ningnanmycin, thiaamide, methidazine or salicylic acid, pyriminomycin, dichloroisonicotinic acid, probenazole, validamine, validamycin; the total mass percentage content of the chiral piperidine derivative I in the antiviral composition is 1-90%, and the ratio of the chiral piperidine derivative I to the commercial anti-plant virus agent is 1-99% to 99-1% by mass; the antiviral composition is processed into a dosage form selected from: seed treatment emulsions, aqueous emulsions, microemulsions, suspoemulsions, capsule suspensions, water soluble granules, fine granules, soluble concentrates, venoms, block baits, granular baits, tablet baits, concentrated baits, sustained release blocks, electrostatic sprays, oil-in-water emulsions, aerosol cans, aerosol candles, aerosol cartridges, aerosol sticks, aerosol tablets, aerosol pellets, gas generants, ointments, hot fogging formulations, cold fogging formulations, aerosols, solid/liquid mixtures, liquid/liquid mixtures, solid/solid mixtures, lacquers, microgranules, chasing powders, oil suspensions, oil dispersible powders, concentrated gels, pour-on formulations, seed coatings, paints, film-forming oils, ultra-low volume liquids, vapor release agents; the antiviral composition can be used for preventing and treating viral diseases selected from: rice dwarf, yellow dwarf, stripe disease, tomato fern leaf virus, pepper mosaic virus, tobacco vein necrosis virus, maize dwarf mosaic, cauliflower mosaic, citrus virus, cymbidium mosaic, cymbidium ringspot virus; the plants for preventing and treating the antiviral composition are selected from the following plants: rice, wheat, barley, oats, corn, sorghum, sweet potato, wood, soybean, sweet broad bean, pea, mung bean, small bean, cotton, silkworm, peanut, rape, sesame, sunflower, sugar beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal, tobacco, tomato, pepper, radish, cucumber, cabbage, celery, tuber mustard, sugar beet, rape, shallot, garlic, watermelon, melon, cantaloupe, papaya, apple, citrus and peach, tea, wild vegetable, bamboo shoot, hop, pepper, banana, papaya, orchid, bonsai.
Table 2 bacteriostatic activity of chiral piperidine derivative I of the invention (inhibition of 50 μ g/ml/%)
| Serial number | Test code | AS | CA | GZ | PP | SS | BC | PI | RC | PS |
| 1 | zyj05-130 | 29.63 | 66.67 | 46.15 | 32.61 | 0 | 43.75 | 34.62 | 68.63 | 15.38 |
| 2 | zyj05-75 | 23.08 | 0 | 25.00 | 57.14 | 30.67 | 33.33 | 60.00 | 60.00 | 19.05 |
| 3 | zyj05-111 | 27.42 | 21.43 | 20.41 | 78.57 | 42.86 | 51.16 | 40.91 | 60.71 | 36.36 |
| 4 | zyj05-137 | 33.33 | 95.24 | 61.54 | 32.61 | 26.92 | 68.75 | 30.77 | 78.43 | 3.85 |
| 5 | zyj05-131 | 44.44 | 61.90 | 38.46 | 63.04 | 57.69 | 56.25 | 57.69 | 74.51 | 7.69 |
| 6 | zyj05-139-3 | 22.22 | 33.33 | 19.23 | 69.57 | 42.31 | 56.25 | 57.69 | 70.59 | 7.69 |
| 7 | zyj05-139-4 | 37.04 | 42.86 | 42.31 | 60.87 | 50.00 | 75.00 | 23.08 | 66.67 | 61.54 |
| 8 | zyj05-133-1 | 40.74 | 47.62 | 50.00 | 69.57 | 96.15 | 75.00 | 38.46 | 68.63 | 42.31 |
| 9 | zyj05-133-2 | 22.22 | 23.81 | 34.62 | 54.35 | 38.46 | 62.50 | 15.38 | 60.78 | 7.69 |
| 10 | zyj05-138 | 29.63 | 47.62 | 26.92 | 58.70 | 38.46 | 56.25 | 30.77 | 68.63 | 19.23 |
| 11 | zyj05-140 | 26.00 | 30.05 | 26.55 | 42.70 | 35.67 | 43.26 | 30.54 | 52.50 | 15.28 |
| 12 | lfy006-39 | 33.33 | 11.11 | 44.83 | 42.25 | 61.40 | 31.58 | 67.50 | 68.29 | 10.00 |
| 13 | lfy004-47 | 16.67 | 27.78 | 44.83 | 74.65 | 52.63 | 100 | 88.75 | 68.29 | 27.50 |
TABLE 3 fungicidal Activity of the chiral piperidine derivative I of the present invention against resistant Botrytis cinerea mutants (inhibition rate,%, 50 mg/l)
| Medicament | T3-10 | T1-12 | FJ1-10 | BC2 |
| Trifloxystrobin | 66.00 | 87.30 | 59.26 | 80.33 |
| zyj05-25 | 100 | 92.06 | 100 | 93.44 |
| zyj05-83 | 77.78 |
TABLE 4 insecticidal Activity of the chiral piperidine derivatives I of the present invention against aphids (mortality,%, 100 mg/l)
| Serial number | Test code | The mortality rate is% | Numbering | Compound (I) | The mortality rate is% |
| 1 | zyj05-130 | 45.75 | 8 | zyj05-133-1 | 65.28 |
| 2 | zyj05-75 | 24.41 | 9 | zyj05-133-2 | 30.33 |
| 3 | zyj05-111 | 32.03 | 10 | zyj05-138 | 55.36 |
| 4 | zyj05-137 | 40.35 | 11 | zyj05-140 | 28.92 |
| 5 | zyj05-131 | 48.62 | 12 | lfy006-39 | 0 |
| 6 | zyj05-139-3 | 30.28 | 13 | lfy004-47 | 74.60 |
| 7 | zyj05-139-4 | 60.57 |
Claims (3)
1. A chiral piperidine derivative is characterized by having a chemical structural general formula shown as a formula I:
wherein A is selected from propionyl and 1-hydroxypropyl; r1Selected from 2- (4' -piperidine) thiazol-4-yl, 4-methylthiazol-5-yl, thiazol-4-yl; r2Is selected from 4-methoxyphenyl, phenyl and 4-nitrophenyl.
2. Use of a chiral piperidine derivative I according to claim 1 together with agriculturally acceptable adjuvants in the preparation of a pesticide.
3. Use of the chiral piperidine derivative I of claim 1 in combination with an agriculturally acceptable adjuvant for the preparation of a fungicide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610402572.1A CN107459514B (en) | 2016-06-06 | 2016-06-06 | Chiral piperidine derivative and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610402572.1A CN107459514B (en) | 2016-06-06 | 2016-06-06 | Chiral piperidine derivative and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107459514A CN107459514A (en) | 2017-12-12 |
| CN107459514B true CN107459514B (en) | 2020-10-23 |
Family
ID=60545902
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610402572.1A Expired - Fee Related CN107459514B (en) | 2016-06-06 | 2016-06-06 | Chiral piperidine derivative and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107459514B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113004263B (en) * | 2021-03-11 | 2024-01-26 | 陕西大美化工科技有限公司 | 4-thiophene ring substituted pyridine derivative and application thereof in pesticides |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102459246A (en) * | 2009-04-07 | 2012-05-16 | 阿斯利康(瑞典)有限公司 | Method and apparatus for producing heat energy and carbon dioxide |
| CN105622597A (en) * | 2016-01-26 | 2016-06-01 | 南开大学 | Chloroisothiazole neonicotine compound, as well as preparation method and application thereof |
-
2016
- 2016-06-06 CN CN201610402572.1A patent/CN107459514B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102459246A (en) * | 2009-04-07 | 2012-05-16 | 阿斯利康(瑞典)有限公司 | Method and apparatus for producing heat energy and carbon dioxide |
| CN105622597A (en) * | 2016-01-26 | 2016-06-01 | 南开大学 | Chloroisothiazole neonicotine compound, as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| [4+2] Annulation of Vinyl Ketones Initiated by a Phosphine-Catalyzed Aza-Rauhut–Currier Reaction: A Practical Access to Densely Functionalized Tetrahydropyridines;Zugui Shi，等;《Chem. Eur. J.》;20121231;第18卷;第9804页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107459514A (en) | 2017-12-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105622422B (en) | A kind of bromo hexahydro indanone compounds and its production and use | |
| CN109970650A (en) | Pyrazole phenyl formamide analog derivative and its preparation method and application | |
| US11166460B2 (en) | α-amino acrylate microbicide, and preparation method therefor and uses thereof | |
| CN105622597A (en) | Chloroisothiazole neonicotine compound, as well as preparation method and application thereof | |
| CN110041260A (en) | A kind of multi-substituted pyrazol amide derivatives and its preparation method and application | |
| US11716992B2 (en) | 5A5B6C tricyclic spirolactone derivative, preparation method therefor and use thereof | |
| CN109970653A (en) | Methoxy acrylate derivative and its preparation method and application of the one kind containing difluoromethyl pyrazole | |
| CN110128419A (en) | A kind of difluoro pyrazole heterocycle carboxamides derivatives and its preparation method and application | |
| CN101891709B (en) | 5-halogenated methyl-1,2,3-thiadiazole compound and preparation method and use thereof | |
| CN112939980A (en) | 3, 4-dichloroisothiazole heterocyclic purine derivatives and preparation method and application thereof | |
| CN107459509B (en) | Nitrogenous and sulphurous sulfimide derivatives and preparation method and application thereof | |
| CN107459514B (en) | Chiral piperidine derivative and preparation method and application thereof | |
| CN104974150B (en) | A kind of carboxamidine derivatives of 3,4 2 chloroisothiazole 5 and its production and use | |
| CN113929696A (en) | Acylthiourea psoralen derivatives, and preparation method and application thereof | |
| CN110128346A (en) | A kind of biaryl amide pyrazole derivatives and its preparation method and application | |
| CN113880863B (en) | 1,2, 4-triazole [3,4-b ] -1,3, 4-thiadiazine derivatives, and preparation method and application thereof | |
| CN112358474A (en) | Difluoropyrazole thiazole methanamide derivatives and preparation method and application thereof | |
| CN112480103A (en) | Coumarin derivatives containing 3, 4-dichloroisothiazole and preparation method and application thereof | |
| CN107602547A (en) | Heterocycle triazole derivative and its production and use | |
| CN102633746A (en) | Di-hydrazide derivatives containing 5-methyl-1, 2, 3-thiadizole and preparation method and application of di-hydrazide derivatives containing 5-methyl-1, 2, 3-thiadizole | |
| US10906880B2 (en) | Kind of isothiazole oxime ether-containing strobilurin derivatives and its preparation methods and application | |
| CN108191787A (en) | A kind of isothiazole imdazole derivatives and its preparation method and application | |
| CN110041324A (en) | A kind of thiadiazoles and isothiazole amide derivatives and its preparation method and application | |
| CN108640887B (en) | Heterocyclic morpholine derivatives, and preparation method and application thereof | |
| CN103214475A (en) | Alpha-(substituted)oxyamide derivatives containing 4-methyl-1,2,3-thiadiazole and preparation methods and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20201023 Termination date: 20210606 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |