CN105541748B - 1,3,4 oxadiazole Mannich base class compounds and preparation and application containing piperazine - Google Patents
1,3,4 oxadiazole Mannich base class compounds and preparation and application containing piperazine Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
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- 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
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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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
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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
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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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- General Health & Medical Sciences (AREA)
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Abstract
The invention discloses 1,3,4 oxadiazole Mannich base class compounds of the class containing piperazine and preparation and application.The compounds of this invention has R in the structural formula as shown in formula I and II, formula1And R2Defined with claim 1.The formula I and Compounds of formula II of the present invention has efficient KARI enzyme inhibition activities, it may have higher activity of weeding, particularly to dicotyledon rape activity significantly.Also there is certain bactericidal activity simultaneously, have in vitro inhibitory activity to cucumber fusarium axysporum, peanut Cercospora bacteria, Botryosphaeria berengeriana f. sp, rhizoctonia cerealis, tomato early blight bacterium and fusarium graminearum etc., it is especially notable to rhizoctonia cerealis effect.The present invention is applied to the efficient suppression to KARI enzymatic activitys, and the integrated control to crop smothering and fungus damage on various crops.
Description
Technical field
The invention belongs to farm weeding, bactericide field, it is related to the synthesis and application of KARI enzyme inhibitors, and in particular to one
Plant the 1,3,4- oxadiazoles Mannich base class compound containing piperazine structure and its preparation and application.
Background technology
The preventing and treating of weeds and phytopathogen in agriculture, woods, herd, in the implementation process of the every profession and trade such as secondary, fishing and public health
It is extremely important, and the use of agricultural chemicals occupies very important effect.Influence to ecological, environment, is that New pesticides discovery is faced
Essential importance, this needs scientists to develop new efficient, low toxicity, safety and with the different modes of action
Pesticide species.
The biosynthesis pathway for being proved branched-chain amino acid in practice is the Effective target site of herbicide molecular design.Ketone
Alkyd reduction isomerase (keto-acid reductoisomerase, KARI) is plant, branched-chain amino acid in microbial body
The key enzyme of second step in biosynthesis pathway, by suppressing KARI activity, can prevent the synthesis of branched-chain amino acid, by it
Applied in weeds body then can biorational design target KARI herbicide, it may also be used for design bactericide.It is so far
Only, the KARI inhibitor type and quantity reported are rare, predominantly Hoe 704, IpOHA, cyclopropanes(For example
CPD), 1,2,3- thiadiazole etc., but these inhibitor are to the active poor of weeds, to the active rare report of phytopathogen
Road, therefore also larger research space.1,3,4- oxadiazole is a class 5-member heterocyclic ring containing nitrogen, many chemical combination containing its structure
Thing has extensive bioactivity, such as sterilization, weeding, desinsection.Piperazine can synthesize fluorine piperazine as important pharmaceutical intermediate
Acid, rifampin, Ofloxacin, Lomefloxacin etc., it is extremely common in medical research field.Piperazine ring is introduced in compound structure past
Toward drug effect can be increased, moreover it is possible to effectively the alkalescence of the lipid of regulating drug and acid-base balance constant increase molecule and
Water solubility, so as to increase the activity of molecule.1,3,4- oxadiazole Mannich base class chemical combination of the class that the present invention is reported containing piperazine
The preparation method of thing, and its KARI enzyme inhibition activities, activity of weeding and bactericidal activity, this is in the prior art there is not yet open.
The content of the invention
It is an object of the invention to provide a kind of 1,3,4- oxadiazoles Mannich base class compound containing piperazine and preparation side
Method and application.The Mannich base class compound has efficient KARI enzyme inhibition activities, can be applied to crop smothering on various crops and
The integrated control of fungus damage.
The 1,3,4- oxadiazole Mannich base classes compound containing piperazine that the present invention is provided has as shown in formula I and II
Structural formula:
In formula:
R1It is unsubstituted, monosubstituted, polysubstituted aryl or heteroaryl, the monosubstituted base or multi-substituent are lower alkyls
Base, lower alkoxy, low-grade halogenated alkyl, halogen atom, nitro, cyano group;Heteroaryl is to contain one or more N, O, S hetero atoms
5 yuan of rings or 6 yuan of rings, including:Furans, thiophene, pyrazoles, imidazoles, triazole, pyridine, pyrimidine, pyrazine, pyridazine;Aryl is mainly benzene
Base;
R2It is low alkyl group, benzyl, substituted benzyl, phenyl, substituted-phenyl, pyrimidine radicals, substituted pyrimidyl, pyridine radicals, takes
For pyridine radicals, the substituent on the substituted benzyl, substituted-phenyl, substituted pyrimidyl and substituted pyridinyl is low alkyl group, low
Level haloalkyl or halogen atom, described substitution is monosubstituted or polysubstituted;
Term " low alkyl group " be methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, the tert-butyl group,
Cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl;
Term " lower alkoxy " be methoxyl group, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutoxy,
Sec-butoxy, tert-butoxy, ring propoxyl group, cyclobutoxy group, cyclopentyloxy, cyclohexyloxy;
The carbon skeleton of term " low-grade halogenated alkyl " is identical in defined low alkyl group therewith, herein under the premise of it is rudimentary
Haloalkyl is that the hydrogen atom on low alkyl group partly or entirely can be replaced by halogen atom;
Described halogen atom is fluorine, chlorine, bromine or iodine.
The general formula compound I of the present invention can be prepared by following method, and substituent therein is outer as before unless specified otherwise
Limited.
Formula III compound is mixed with formula IV compound with organic solvent, 37% formaldehyde is added(HCHO)The aqueous solution, stirring
Reaction.Suction filtration goes out solid after solid that suction filtration is born or concentration, is recrystallized with organic solvent, or directly washed with the organic solvent
Wash to obtain compound of formula I.Reaction temperature can be low temperature to solvent boiling point temperature, usually 0oC ~ 78 oC;Reaction time is usual
For 0.5 ~ 3 hour;The organic solvent be methanol, ethanol, propyl alcohol, dichloromethane, tetrahydrofuran, 1,4- dioxane orN,N- dimethylformamide;The formula III compound, formula IV compound, HCHO mol ratio are usually 1: 1 ~ 1.15: 2 ~ 5.
Compounds of formula III can be according to document(Eur. J. Med. Chem.,2010,45, 4963.)Operate into
It is prepared by row.Formula IV(1- substituted-piperazinyls)Part of compounds it is commercially available.The preparation of formula IV part of compounds may be referred to
Document(J. Chem. Res., 2006, 12, 809.)In method carry out.
General formula compound II can be prepared by following method, and substituent therein is outer unless specified otherwise to be limited as before.
Formula III compound and Piperazine anhydrous are mixed with organic solvent, 37% formaldehyde is added(HCHO)The aqueous solution, stirring is anti-
Should.The solid that suction filtration is born, is recrystallized with organic solvent, or Formula II compound is directly obtained with organic solvent washing.Reaction temperature
Degree can be low temperature to solvent boiling point temperature, usually 0oC ~ 78 oC;Reaction time is usually 0.5 ~ 2 hour;It is described to have
Machine solvent be methanol, ethanol, propyl alcohol, dichloromethane, tetrahydrofuran, 1,4- dioxane orN,N- dimethylformamide;It is described
Formula III compound, Piperazine anhydrous, HCHO mol ratio are usually 1: 0.5: 1.5 ~ 3.
The formula I and Compounds of formula II of the present invention has efficient KARI enzyme inhibition activities, it may have higher weeding
Activity, particularly to dicotyledon rape activity significantly.Simultaneously also have certain bactericidal activity, to cucumber fusarium axysporum,
Peanut Cercospora bacteria, Botryosphaeria berengeriana f. sp, rhizoctonia cerealis, tomato early blight bacterium and fusarium graminearum etc. have in vitro suppression
Activity is especially notable to rhizoctonia cerealis effect.Therefore, efficiently press down for KARI enzymes present invention additionally comprises general formula compound
Preparation, and control the purposes of plant crop smothering and fungus damage.
Present invention additionally comprises be used as the weeding of active component or bactericidal composition using formula I and Compounds of formula II.This is removed
Also including acceptable carrier in agricultural, forestry, health in grass or bactericidal composition.
There is a kind of 1,3,4- oxadiazole Mannich base class compounds containing piperazine that the present invention is provided efficient KARI enzymes to press down
System activity, can be applied to the integrated control to crop smothering and fungus damage on various crops.
Embodiment
The present invention is further illustrated with reference to embodiments, the purpose is to be better understood when that present disclosure is body
The substantive distinguishing features of the existing present invention, therefore the cited case is not construed as limiting the scope of the invention.Here also refer in particular to
Go out specific experiment method and apparatus involved in embodiment unless otherwise specified, be conventional method or said according to manufacturer
The condition of bright book suggestion is implemented, and involved reagent is commercially available without specified otherwise.
Embodiment 1
The preparation method of compound 01
Step 1:Prepare 5- (furans -2- bases) -1,3,4- oxadiazole -2- mercaptan
9.00 g (71.37 mmol) furans -2- formylhydrazines and the anhydrous second of 300 mL are added in 500mL round-bottomed flasks
Under alcohol, ice bath stirring condition, 21.66 g (285.7 mmol) carbon disulfide is slowly added to, then again by 4.00 g (71.37
Mmol) KOH is added portionwise in reaction system, is slowly heated up after being stirred at room temperature 5 minutes, is flowed back 7 hours.Revolving removes solvent,
Residue water dissolves, and then adjusts pH to 2 ~ 3 with watery hydrochloric acid, is stirred at room temperature 0.5 hour, suction filtration, ethyl alcohol recrystallization obtains white
Color solid 8.51g, yield 72%.
Step 2:Preparation 3- ((4- (4- chlorobenzyls) piperazine -1- bases) methyl) -5- (furans -2- bases) -1,3,4- oxadiazoles -
2(3H)-thioketones(01)
In 50mL round-bottomed flasks, 0.25 g (1.49 mmol) 5- (furans -2- bases) -1,3,4- oxadiazole -2- is added
Mercaptan, 0.37 g (1.49 mmol) 1- (4- chlorobenzyls) piperazines and 15 mL absolute ethyl alcohols, 0.45g is added after stirring and evenly mixing
(5.55 mmol) 37% formalin, is stirred at room temperature 1 hour, and suction filtration is washed with a small amount of absolute ethyl alcohol, is dried, is obtained colourless crystalline substance
The g of body 0.41, yield 71%.
Embodiment 2
Compound 06(Double (5- (furans -2- the bases) -1,3,4- oxadiazoles -2 of 3,3 '-(piperazine -1,4- diyls dimethylene)
(3H)-thioketones))Preparation method
In 50mL round-bottomed flasks, 0.50 g (2.98 mmol) 5- (furans -2- bases) -1,3,4- oxadiazole -2- is added
Mercaptan, 0.13 g (1.49 mmol) Piperazine anhydrous and 15 mL absolute ethyl alcohols, add 0.45 g (5.55 after stirring and evenly mixing
Mmol) 37% formalin, is stirred at room temperature 1 hour, and suction filtration is washed with a small amount of absolute ethyl alcohol, is dried, is obtained clear crystal 0.50
G, yield 76%.
Embodiment 3
The preparation method of compound 09
Step 1:Prepare 5- (pyridin-3-yl) -1,3,4- oxadiazole -2- mercaptan
17.00 g (123.9 mmol) 3- pyridinecarboxylics hydrazines and the anhydrous second of 100 mL are added in 250 mL round-bottomed flasks
Alcohol, in ice bath (0oC under) stirring, 37.83 g (324.3 mmol) CS is added2With 6.93 g (123.9 mmol) KOH, plus
Material finishes recession and removes ice bath, is heated to reflux 10 hours.It is cooled to room temperature rotation and removes solvent, residue is adjusted after being dissolved with water with hydrochloric acid
PH to 2 ~ 3, is stirred 2 hours, suction filtration, ethyl alcohol recrystallization obtains 9.10 g white solids, yield 41%.
Step 2:Prepare 3- ((4- (2,4- dichloro benzyls) piperazine -1- bases) methyl) -5- (pyridin-3-yl) -1,3,4- Evil
Diazole -2 (3H)-thioketones(09)
In 50mL round-bottomed flasks, 0.25 g (1.40 mmol) 5- (pyridin-3-yl) -1,3,4- oxadiazole -2- is added
Mercaptan, 0.34 g (1.40 mmol) 1- (2,4- dichloro benzyl) piperazines and 15 mL absolute ethyl alcohols, are added after stirring and evenly mixing
0.45g (5.55 mol) 37% formalin, is stirred at room temperature 1 hour, suction filtration is washed with a small amount of absolute ethyl alcohol, dries, obtains nothing
The g of color crystal 0.48, yield 79%.
Embodiment 4
The preparation method of compound 19
Step 1:Prepare 5- (3,4,5- trimethoxy -2- nitrobenzophenones) -1,3,4- oxadiazole -2- mercaptan
Added in 50 mL round-bottomed flasks 1.36 g (5.00 mmol) 3,4,5- trimethoxies -2- nitrobenzoyls hydrazides and
20 mL absolute ethyl alcohols, in ice bath (0oC) under stirring condition, it is slowly added to 1.52 g (20.00 mmol) CS2With 0.28 g
(5.00 mmol) KOH, charging finishes recession and removes ice bath, is heated to reflux 7 hours.It is cooled to room temperature rotation and removes solvent, residue adds
Enter after suitable quantity of water dissolving with salt acid for adjusting pH to 2 ~ 3, stir 2 hours, suction filtration, ethyl alcohol recrystallization obtains 1.46 g light yellow solid
Body, yield 93%.
Step 2:Prepare 3- ((4- (pyridine -2- bases) piperazine -1- bases) methyl) -5- (3,4,5- trimethoxy -2- nitrobenzene
Base) -1,3,4- oxadiazoles -2 (3H)-thioketones(19)
Added in 50 mL round-bottomed flasks 0.31 g (1.00 mmol) 5- (3,4,5- trimethoxy -2- nitrobenzophenones) -
1,3,4- oxadiazole -2- mercaptan and 10 mL absolute ethyl alcohols, dissolve by heating, 0.16 g (1.00 mmol) are sequentially added after cooling
1- (pyridine -2- bases) piperazines and 0.40 g (4.93 mmol) 37% formalin, are stirred at room temperature suction filtration after 1 hour, use second
Alcohol is recrystallized, and obtains 0.36 g clear crystals, yield 73%.
Embodiment 5
The preparation method of compound 22
Step 1:Prepare 5- phenyl -1,3,4- oxadiazole -2- mercaptan
19.00 g (139.6 mmol) benzoyl hydrazines and 100 mL absolute ethyl alcohols are added in 250 mL round-bottomed flasks, in ice
Bath (0oC under) stirring, 42.43 g (558.2 mmol) CS is added2With 7.81 g (139.6 mmol) KOH, charging is finished
Ice bath is removed in recession, is heated to reflux 7 hours.It is cooled to room temperature rotation and removes solvent, residue adds suitable quantity of water to use salt acid for adjusting pH after dissolving
To 2 ~ 3, stir 2 hours, suction filtration, ethyl alcohol recrystallization obtains 18.16 g white solids, yield 73%.
Step 2:Preparation 3- ((4- (4- methylpyrimidine -2- bases) piperazine -1- bases) methyl) -5- phenyl -1,3,4- oxadiazoles -
2(3H)-thioketones(22)
0.31 g (1.74 mmol) 5- phenyl -1,3,4- oxadiazole -2- mercaptan, 0.31 are added in 50 mL round-bottomed flasks
G (1.96 mmol) 1- (4- methylpyrimidine -2- bases) piperazines and 10 mL absolute ethyl alcohols, add 0.40 g after stirring and evenly mixing
(4.93 mmol) 37% formalin, is stirred at room temperature reaction 2 hours, suction filtration, solid ethyl alcohol recrystallization obtains 0.45 g white
Color solid, yield 70%.
Embodiment 6
The preparation method of compound 25
Step 1:Prepare 5- (2- fluorophenyls) -1,3,4- oxadiazole -2- mercaptan
The adjacent fluorobenzoyl hydrazines of 5.00 g (32.4 mmol) and 50 mL absolute ethyl alcohols are added in 100 mL round-bottomed flasks,
Ice bath (0oC under) stirring, 9.86 g (129.8 mmol) CS is added2With 1.82 g (32.4 mmol) KOH, charging is finished
Ice bath is removed in recession, is heated to reflux 7 hours.It is cooled to room temperature rotation and removes solvent, residue is adjusted after adding suitable quantity of water dissolving with hydrochloric acid
PH to 2 ~ 3, is stirred 2 hours, suction filtration, ethyl alcohol recrystallization obtains 5.41 g brown solids, yield 85%.
Step 2:Preparation 5- (2- fluorophenyls) -3- ((4- (pyrimidine -2-base) piperazine -1- bases) methyl) -1,3,4- oxadiazoles -
2(3H)-thioketones(25)
In 50 mL round-bottomed flasks, 0.2 g (1.00 mmol) 5- (2- fluorophenyls) -1,3,4- oxadiazole -2- sulphur is added
Alcohol, 0.16 g (1.00 mmol) 1- (pyrimidine -2-base) piperazines and 10 mL absolute ethyl alcohols, add 0.40 g after stirring and evenly mixing
(4.93 mmol) 37% formalin, is reacted at room temperature 2 hours, suction filtration, with ethyl alcohol recrystallization, obtains the g of white solid 0.22, production
Rate 58%.
The compound physical constant now prepared according to the preparation method of embodiment 1~6 using different material is included in
Table 1, the proton nmr spectra of compound(1H NMR)Data are included in table 2.
The target compound of table 1(Formula I and II)Physical constant
The target compound of table 2(Formula I and II)Nmr spectrum data
Biological activity test example
Embodiment 7
The compound provided using the present invention carries out the in vitro inhibitory activity test of KARI enzymes.
Method of testing:The Bacillus coli cells converted using recombinant plasmid (containing paddy rice KARI enzyme genes) are come high-volume
Expressing K ARI enzymes, the interaction of research compound and KARI enzymes uses dynamic-analysis method under conditions of in vitro, will
Appropriate inhibitor solution, 0.1 mol/L Tris-HCl buffer solutions (pH=8.0), 0.2 mmol/L NADPH, 1 mmol/L
MgCl2And appropriate paddy rice KARI zymoproteins are mixed in cuvette, are incubated 10 minutes in 30 DEG C, addition contains
The acetolactic mixed liquors of 0.1 mmol/L start enzyme reaction, with slope (the Δ OD of initial reaction stage linear change part340/
Min initial enzyme activity) is represented, 340 nm of continuous record absorbance (monitoring NADPH abatement) can obtain inhibitor
Inhibiting rate is calculated to the activity suppression curve of KARI enzymes, and then with blank control, 3 are the results are shown in Table.With inhibitor concentration and just
Beginning enzymatic activity is respectivelyX WithY, making nonlinear regression analysis, (mathematical formulae is:Y=A/ (1+X/B), calculate suppression normal
NumberK i, as shown in table 4.
The in vitro inhibitory activity data of partial target compound K ARI enzymes (200 mg/L) of table 3
Inhibition constant of the partial target compound of table 4 to KARI enzymes
Embodiment 8
The compound provided using the present invention carries out the measure of activity of weeding.
Rape Plating:Complete a cm of diameter 5.6 filter paper respectively in two groups of diameter 6cm culture dish, add respectively
Enter 2 milliliter of 10 μ g/mL and 100 μ g/mL test compounds solution(Solvent DMF), add the rape seed 10 of seed soaking 6 hours
Grain, 28 ± 1oUnder C, dark culturing determines radicle length after 72 hours, the life by compound under dark condition to rape radicle
The long activity of weeding for suppressing to carry out detection compound, each processing is repeated twice, and is compared and is inhibited with blank control group
Rate(Formula is as follows).Activity index:Embryo root colonization(%), the results are shown in Table 5.
Barnyard grass small-radius curve track:After completing bead and filter paper respectively in two groups 50 milliliters of small beaker, 6 milliliters are separately added into
10 μ g/mL and 100 μ g/mL test compounds solution(Solvent DMF), 10, the barnyard grass seed just showed money or valuables one carries unintentionally, 28 ± 1oC
Under, illumination cultivation determines the height of seedling after 72 hours, the growth of barnyard grass Seedling Height is pressed down by compound under illumination condition
System carrys out the activity of weeding of detection compound, and each processing is repeated twice, and is compared the rate of being inhibited with blank control group(It is public
Formula is as follows).Activity index:Height growth inhibiting rate(%), the results are shown in Table 5.
The Herbicide activity data of the part of compounds of table 5(Inhibiting rate %, 100 μ g/mL)
Embodiment 9
The compound provided using the present invention carries out in vitro bactericidal activity test.
Test target:Under 50 μ g/mL concentration, to cucumber fusarium axysporum, peanut Cercospora bacteria, Botryosphaeria berengeriana f. sp,
6 kinds of plant pathogenic fungis such as rhizoctonia cerealis, tomato early blight bacterium and fusarium graminearum carry out antibacterial test.
Method of testing:It will be broken into for examination germ in culture dish of the bacterium piece access containing 50 μ g/mL decoctions, be put into 25oC is biochemical
Dark culturing in incubator, after 72 hours, measures colony diameter, and be compared the rate of being inhibited with blank control group(Formula
It is as follows).Using only plus sterilized water not adding medicine person for compare.It the results are shown in Table 6.
The in vitro bactericidal activity data of the compound of table 6(Inhibiting rate %, 50 μ g/mL)
Claims (7)
1. a kind of 1,3,4- oxadiazole Mannich base class compounds containing piperazine, with the structural formula as shown in formula I and II:
It is characterized in that:
R1It is 2- fluorophenyls, 3,4,5- trimethoxy -2- nitrobenzophenones, furans -2- bases, pyridin-3-yl;
R2It is that benzyl, 4- chlorobenzyls, 2,4- dichloro benzyls, phenyl, pyridine -2- bases, 4- methylpyrimidine -2- bases, 4,6- dimethyl are phonetic
Pyridine -2- bases.
2. 1 containing piperazine described in claim 1, the preparation method of 3,4- oxadiazole Mannich base class compounds, its feature exists
Mixed in by formula III compound with formula IV compound with organic solvent, add 37% formalin, stirring reaction;Reaction temperature
For 0 DEG C ~ 78 DEG C;Reaction time is 0.5 ~ 3 hour, after the completion of reaction, by suction filtration after the solid suction filtration of generation or concentration,
Solid is recrystallized with organic solvent, or directly obtains compound of formula I with the organic solvent washing, and reaction equation is as follows:
R in formula1、R2Defined with claim 1;The formula III compound, formula IV compound, the mol ratio of formaldehyde are 1: 1
~ 1.15∶2 ~ 5。
3. 1 containing piperazine described in claim 1, the preparation method of 3,4- oxadiazole Mannich base class compounds, its feature exists
Mixed in by formula III compound and Piperazine anhydrous with organic solvent, add 37% formalin, stirring reaction;Reaction temperature is
0 ℃ ~ 78 ℃;Reaction time is 0.5 ~ 2 hour, and after the completion of reaction, the solid suction filtration of generation is tied again with organic solvent
Crystalline substance, or Formula II compound directly is obtained with the organic solvent washing, reaction equation is as follows:
R in formula1、R2Defined with claim 1;The formula III compound, Piperazine anhydrous, the mol ratio of formaldehyde are 1: 0.5:
1.5 ~ 3。
4. the preparation method according to Claims 2 or 3, it is characterised in that the organic solvent be methanol, ethanol, propyl alcohol,
Dichloromethane, tetrahydrofuran, 1,4- dioxane orN,N- dimethylformamide.
5. the 1,3,4- oxadiazole Mannich base classes compound containing piperazine described in claim 1 is used to manufacture KARI enzyme levels
Agent.
6. the 1,3,4- oxadiazoles Mannich base class compound containing piperazine described in claim 1 is used as the weeding of active component
Or bactericidal composition;And also including acceptable carrier in agricultural, forestry, health in the weeding or bactericidal composition.
7. the 1,3,4- oxadiazole Mannich base classes compound containing piperazine described in claim 1 is used for careless on various crops
The purposes of the preventing and treating of evil and fungus damage.
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