CN1594294A - Cyanoacrylate compounds containing fluoro pyridine-methylamino group and their bioactivity - Google Patents
Cyanoacrylate compounds containing fluoro pyridine-methylamino group and their bioactivity Download PDFInfo
- Publication number
- CN1594294A CN1594294A CN 200410019757 CN200410019757A CN1594294A CN 1594294 A CN1594294 A CN 1594294A CN 200410019757 CN200410019757 CN 200410019757 CN 200410019757 A CN200410019757 A CN 200410019757A CN 1594294 A CN1594294 A CN 1594294A
- Authority
- CN
- China
- Prior art keywords
- reaction
- alkyl
- fluoro
- mol ratio
- compound
- 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.)
- Granted
Links
Landscapes
- Pyridine Compounds (AREA)
Abstract
The invention Cyanoacrylate compounds containing fluoro pyridine-methylamino group and their grass-clearing activity, wherein the compound (I) high very high Hill reaction activity and grass-clearing activity, and exhibits fine selectivity for crops, wherein R1 is alkyl, alkoxy, aralkyl, R2 is alkyl or alkyl sulfide.
Description
Technical field
The present invention relates to the cyanoacrylate compound and the weeding activity of fluorinated pyridine methylamino-.
Background technology
Photosynthesis is high green plants and the distinctive important physical biological process of some mushroom, and animal does not have, and considers that from toxicity this selectivity for the photosynthesis weedicide provides solid basis.All have, and to suppress the active compound of photosynthesis all be to have destroyed photoresponse or blocked electron transport in the photosynthesis process.What research was maximum in the inhibitor of photosynthesis is electron transfer inhibitor.
Cyanoacrylate is a class special P SII electron transfer inhibitor, and relevant this electron-like transmits studies show that of inhibitor: it is very remarkable that the variation that this compounds is structurally trickle suppresses activity influence to Hill reaction.For example, introduce the ether structure group that has bigger electronegative Sauerstoffatom in the lateral chain of ester group, the stereoeffect of β position alkyl, and the methylene radical number between aromatic ring and amido, these can both significantly influence the inhibition activity of cyanoacrylate compound.
Cyanoacrylate compound and amides, phenol PSII electron transfer inhibitor be the same to act on QB combining site in the D1 albumen of PSII, and nineteen ninety Mcfadden and Phillps have confirmed this point by the method for mark.
Nineteen ninety, Huppatz etc. have carried out QSAR research to the Hill reaction inhibition activity of the cyanoacrylate compound of following three class formations.
Used alpha-cyanoacrylate ester structure in the QSAR research
Dependent equation is respectively:
I???pI
50＝1.17(±0.18)π+4.86(±0.50)?????n＝13????r＝0.96
II??pI
50＝1.08(±0.22)π+6.29(±1.01)?????n＝27????r＝0.86
III?pI
50＝-0.18(±0.09)MR+8.27(±1.51)????n＝11????r＝0.82
Equation I and II show, the pI of this two classes cyanoacrylate
50Do not have obvious correlationship with substituent electrical property feature σ and substituting group size MR, promptly only substituent hydrophobicity affects the inhibition activity of compound.For the QSAR research of III class alpha-cyanoacrylate ester cpds, dependent equation shows that the big or small MR of meta-substituent influences compound to suppress activity value pI
50Negative factor, the substituting group at this position changes only influence the Hill reaction and suppresses activity on steric factor.
Study as can be seen from the QSAR of above three class cyanoacrylate compound, the inhibition activity of this class PSII electron transfer inhibitor more depends on the steric factor of each substituting group generation and the influence of hydrophobicity factor, and a little less than the electrical influence.Perhaps this is the cause that cyanoacrylate itself has possessed certain electrical property feature.
Chinese patent CN1089089A had reported cyanoacrylate compound and the biological activity that contains sulfenyl pyridyl-methanamine base in 2002.(structure is as follows :)
R
1=CN, CO
2X, CONY R
2=alkyl, benzyl
X is an alkyl, alkoxyalkyl, alcoxyl alkoxyalkyl, alkane sulfane base; Y is an alkoxyalkyl
Successfully pyridine heterocycle has been replaced common phenyl ring, resulting compound has very high Hill reactive behavior and weeding activity, and crop is shown good selectivity.To corn growth safety.It can be used as Amaranthus retroflexus broadleaf weeds and barnyard grass grass in the corn field, the weedicide of weeds such as lady's-grass Gramineae under 20-100 gram/mu dosage.
Chinese patent CN 1483320A discloses a kind of heterocycle methylamino cyanoacrylate compound and weeding activity of containing, it is further cyanoacrylate compound to be carried out composition optimizes, pyridine chlorine in ring atom is contained heteroatomic group (as fluorine, chlorine, bromine, alkoxyl group, alkylthio, alkylamino radical etc.) with other to be replaced, perhaps pyridine ring is changed into other heterocycle (as thiazole, pyrimidine, furans, pyrroles, thiophene, oxazole, thiazole, imidazoles, pyridazine, pyrazine, triazine etc.), synthesized and contained heterocycle methylamino cyanoacrylate compound (C).Biological activity determination is the result show: Compound C has very high weeding activity to broadleaf weeds and gramineous weeds, and crop is shown good selectivity.
Though above-mentioned document has been put down in writing can the fluorine substituted pyridines, but without any the cyanoacrylate compound of the methylamino-of putting down in writing the fluorine substituted pyridines particularly, more without any the weeding activity of putting down in writing these compounds particularly.
Summary of the invention
The purpose of this invention is to provide a kind of cyanoacrylate compound and their preparation method and application of fluorinated pyridine methylamino-.Compound of the present invention has very high weeding activity to broadleaf weeds and gramineous weeds, and crop is shown good selectivity, to corn growth safety.
The present invention is following general formula (I) compound:
Wherein, R
1Be alkyl, alkoxyalkyl, aryloxyalkyl group, alcoxyl alkoxyalkyl, fragrant oxygen aryloxyalkyl group;
R
2Be alkyl or alkylthio.Above-mentioned alkyl is C
1-C
6Alkyl.
Above-mentioned said R
1Be-C
2H
5O-m-CH
3-Ph ,-C
2H
5O-p-NO
2-Ph ,-C
2H
5O-m-NO
2-Ph-C
2H
5O-m-OCH
3-Ph ,-C
2H
5O-2,4-2Cl-Ph ,-C
2H
5O-o-CF
3-Ph ,-C
2H
5O-2,4-2CH
3, 6-NO
2-Ph ,-C
2H
5O-Ph ,-C
2H
5O-o-Cl-Ph ,-C
2H
5O-C
2H
5, CN or CO
2C
2H
5, R
2Be CH
3S-, PhCH
2S-, C
2H
5-or i-Pr-.
The compounds of this invention (I) synthetic route is as follows:
Concrete synthetic route of the present invention is described in detail as follows:
Cyan-acetic ester or propane dinitrile and dithiocarbonic anhydride, sodium hydroxide or potassium hydroxide (mol ratio 1: 1: 2～2.1) are in dioxane, anhydrous acetonitrile or dehydrated alcohol equal solvent, 0～40 ℃ was reacted 0.5-3 hour down, add haloalkane (X=Cl at 0～40 ℃, Br, 1) or methyl-sulfate (only being used to methylate) (mol ratio 1: 2-2.1), 0～40 ℃ of down reaction about 12 hours.Solid is separated out in the ice-water bath cooling, or the adding elutriation goes out oily matter in reaction system, is intermediate 2-cyano group-3,3-two sulfenyl acrylate or vinyl cyanide.
(mol ratio is 1: 1-1.5) in diacetyl oxide for cyan-acetic ester or propane dinitrile and former propionic acid trimethyl or trimethyl orthoacetate or former isopropylformic acid trimethyl, being heated to 100～140 ℃ reacts after 1-2 hour down, steam lower boiling material, the question response system temperature is raised to 130-140 ℃, continuation was this temperature range reaction 1-2 hour, steam lower boiling material again, the question response system temperature is raised to 130-140 ℃ and continues reaction, reflux temperature up to reaction system arrives about 140 ℃, and keep constant, continued back flow reaction 1-2 hour, cool to room temperature, the sherwood oil that adds 60-90 ℃ in reaction system stirs and separates out solid, filter intermediate 2-cyano group-3-methoxyl group-3 '-alkyl acrylate or vinyl cyanide.
Add 2-fluoro-5-cyanopyridine in autoclave, with the saturated ethanol solution of ammonia, Raney Ni is at 15--100atm H
2, carry out reduction reaction under 20--80 ℃, reaction removes by filter Raney Ni after finishing, and the filtrate carrying out precipitation treatment is removed ethanol and ammonia, and 74-76 ℃/3-5mmHg cut is collected in the residue underpressure distillation, obtains 2-fluoro-5-aminomethyl-pyridine.
2-cyano group-3,3-two sulfenyl acrylate or vinyl cyanide and 2-fluoro-5-aminomethyl-pyridine (mol ratio 1: 1.1-1.2) in dehydrated alcohol or tetrahydrofuran (THF) or chloroform equal solvent, react, backflow 8-12 hour, concentrate.As obtain solid, can obtain target product with the ethyl acetate petroleum ether recrystallization; If obtain oily matter, separate purification with rapid column chromatography, can obtain target product.
2-cyano group-3-methoxyl group-3-alkyl acrylate or vinyl cyanide and 2-fluoro-5-aminomethyl-pyridine (mol ratio 1: 1.1-1.2) in dehydrated alcohol or tetrahydrofuran (THF) or chloroform equal solvent, react, backflow 8-12 hour, concentrate.As obtain solid, can obtain target product with the ethyl acetate petroleum ether recrystallization; If obtain oily matter, separate purification with rapid column chromatography, can obtain target product.
After the present invention replaces benzyl aminopyridine chlorine in ring atom with fluorine atom, the weeding activity of the cyanoacrylate of gained and the selectivity of crop all is enhanced, especially performance is more outstanding on to the selectivity of crop.Compound of the present invention has very high weeding activity to broadleaf weeds and gramineous weeds, and crop is shown good selectivity, to corn growth safety.The present invention can be used as the weedicide of gramineous weedss such as broadleaf weedss such as oily Lay in the corn field, Amaranthus retroflexus and barnyard grass grass, lady's-grass.The direct dispenser in farmland under 5-100 gram/mu dosage.
Substantial characteristics of the present invention can be embodied from following embodiment, but it should not to be considered as be any limitation of the invention.
Embodiment
Embodiment 1:2-cyano group-3,3-diformazan sulfenyl ethyl propenoate synthetic
In the 250ml there-necked flask, add the potassium hydroxide powder (0.25mol) of 17.1 gram porphyrizes, the 100ml dioxane.Be cooled to 0 ℃, drip 14.1 gram ethyl cyanacetates (0.125mol) under the vigorous stirring, 9.5 gram dithiocarbonic anhydride (0.125mol), the 30ml dioxane solution, approximately dropwised, add the back and be raised to room temperature reaction 2-3 hour naturally, stop this reaction with 2 hours, leave standstill, inclining the upper strata dioxane and must consolidate yellow solid.Continuation adds the ethanol of 240ml95%, 40ml water in reaction flask.Stir down that room temperature drips 34.65 gram methyl-sulfates (0.275mol), dropwise with 2-4 hour, continue at room temperature reaction to add 1500ml water about 5 hours in system, yellow solid product is separated out in stirring.
Embodiment 2:2-cyano group-3,3-diformazan sulfenyl vinylformic acid substituted benzene oxygen ethyl ester synthetic
Add 0.0634mol potassium hydroxide and 0.0317mol2-cyano group ethyl phenoxy (1) in the 20mL acetonitrile, drip dithiocarbonic anhydride 0.0317mol behind the 0.5h.Behind the 3h, ice bath drips methyl-sulfate 0.0665mol down, rises to room temperature naturally, and stirring is spent the night.Suction filtration is spin-dried for, recrystallization.
Embodiment 3. 2-cyano group-3,3-diformazan sulfenyl vinylformic acid ethoxy ethyl ester synthetic
In the 100ml there-necked flask, the potassium hydroxide powder (0.04mol) that adds 2.74 gram porphyrizes, and 12ml anhydrous acetonitrile, after being cooled to 5 ℃, drip 2.86 gram cyanoacetic acid ethoxy ethyl esters (0.02mol), 1.5 the mixed solution of gram dithiocarbonic anhydride (0.02mol) and 5ml anhydrous acetonitrile, about 30min drips off, stirring at room 4h.Be cooled to 0 ℃, Dropwise 5 .04 restrains methyl-sulfate (0.04mol), dropwises with 2 hours, continues at room temperature reaction to add 50ml water about 5 hours in system, tells the red oil of generation, is product.
Embodiment 4. 2-cyano group-3,3-two benzylthio-vinyl cyanide synthetic
In the 250ml there-necked flask, add the potassium hydroxide powder (0.25mol) of 17.1 gram porphyrizes, the 80ml dioxane is cooled to 0 ℃, drip the mixed solution of 8.25 gram propane dinitrile (0.125mol), 9.5 gram dithiocarbonic anhydride (0.125mol) and 60ml dioxane under the vigorous stirring, dripped off in about 2 hours.Stirring at room 2 hours is stopped this reaction, leaves standstill, and inclines to the upper strata dioxane and must consolidate yellow solid.Continuation adds the ethanol of 240ml 95%, 40ml water in reaction flask.Stir down that room temperature drips 31.7 gram Benzyl Chlorides (0.25mol), dropwise with 2 hours, continue at room temperature reaction to be heated to 60 ℃ of reactions 3 hours about 2 hours, after ice-water bath fully cools off, add 1500ml water in system, yellow solid product is separated out in stirring.
Synthesizing of embodiment 5. 2-cyano group-3-methoxyl group-3-ethylacrylic acid ethoxy ethyl ester
In the 50ml four-hole bottle, add 0.1mol cyanoacetic acid ethoxy ethyl ester, 0.11mol former propionic acid trimethyl 0.11mol acetic anhydride, being heated to 140 ℃ reacts after 1-2 hour down, steam lower boiling material, the question response system temperature is raised to 130-140 ℃, continuation was this temperature range reaction 1-2 hour, steam lower boiling material again, the question response system temperature is raised to 130-140 ℃ and continues reaction, arrive about 140 ℃ up to the reflux temperature of reaction system, and keep constantly, continued back flow reaction 1-2 hour, cool to room temperature, the sherwood oil that adds 60-90 ℃ in reaction system stirs and separates out solid, filter intermediate 2-cyano group-3-methoxyl group-3 '-ethylacrylic acid ethoxy ethyl ester.
Synthesizing of embodiment 6 6-chloro-nicotinamides
In the 100mL four-hole bottle, add 3.15 gram (0.02moL) 6-chlorine apellagrins, the sulfur oxychloride that 30mL heavily steams, calcium chloride drying, tail gas absorbs, and reflux is until there not being gas to emit, this moment, reaction solution became glassy yellow, stopped reaction steams excessive sulfur oxychloride, obtains 6-chloronicotinoyl chloride (1), in residue, add the methylene dichloride that 20mL heavily steams, cryosel is bathed down, feeds the exsiccant ammonia, occurs a large amount of white solids immediately, turn green until the pH test paper, stop logical ammonia, continue to react half an hour at low temperatures, after having reacted, filter, washing, drying, the solid 2.95 that obtains white restrains.Two step total recoverys 93.95%.M.p=208-210 ℃ (document is 214-216 ℃).
Synthesizing of embodiment 7 2-chloro-5-cyanopyridines
Method 1:6-chloro-nicotinamide is through POCl
3Evaporation
In being housed, churned mechanically 500mL four-hole bottle adds 30 gram (0.192moL) 6-chloro-nicotinamides, the POCl that 100mL heavily steams
3, the chloroform that 300mL heavily steams, reflux, reaction solution gradually becomes clarification by muddiness, and has a large amount of gas to emit, and no gas is emitted the back stopped reaction, steams excessive POCl
3And chloroform, under agitation add a large amount of cold water, to filter, washing obtains brown solid, the solid ethyl alcohol recrystallization, decolorizing with activated carbon obtains white solid 18.49 grams.Yield 69.57%.M.p=116-118 ℃ (document is 117-118 ℃).
Method 2:6-chloro-nicotinamide is through P
2O
5Evaporation
In the pyriform bottle of 10mL, add 5.44 gram (0.035moL) 6-chloro-nicotinamides, the P that 5 grams (0.04moL) pulverize
2O
5, make its thawing under the thorough mixing, high temperature, the limit pyroreaction, the limit underpressure distillation obtains white solid 3.9 grams.Yield 49.79%.M.p=116-118 ℃ (document is 117-118 ℃).
Synthesizing of embodiment 8 2-fluoro-5-cyanopyridines
Add 9.01 gram (0.065moL) 2-chloro-5-cyanopyridines in churned mechanically 100mL four-hole bottle is housed, 60mLDMF adds 9.63 grams (0.166moL) KF of baking newly in the time of 115 ℃, remain on 120 ℃ of reaction 12h.Reaction naturally cools to room temperature after finishing, and adds the saturated trash ice of a large amount of NaCl of using, and occurs a large amount of khaki color solids immediately, filters, and washing with acetone and sherwood oil recrystallization, decolouring, obtains faint yellow solid 5.35 and restrains (GC content 94.59%).Yield 63.82%.M.p=51-52 ℃ (document is 51 ℃).
Embodiment 9 2-fluoro-5-aminomethyl-pyridines are synthetic
In autoclave, add 6.2 gram (0.05mol) 2-fluoro-5-cyanopyridines, the 60mL saturated dehydrated alcohol of ammonia, 6.8 gram Raney Ni are at 15atm H
2, carry out reduction reaction under 40 ℃, reaction removes by filter RaneyNi after finishing, and the filtrate carrying out precipitation treatment is removed ethanol and ammonia, and 74-76 ℃/3-5mmHg cut is collected in the residue underpressure distillation, obtains water white 2-fluoro-5-aminomethyl-pyridine liquid.
Synthesizing of embodiment 10 2-cyano group-3-methylthio group-3-(2 '-fluoro-5 '-pyridine) methylamino-vinylformic acid-3-nitro-phenoxy ethyl ester
In the 100mL four-hole bottle, add the 2-cyano group-3 of 0.261 gram (0.001mol), 3-diformazan sulfenyl vinylformic acid 3-nitro-phenoxy ethyl ester, 10mLTHF, low temperature drip the 10mLTHF solution of 0.126 gram (0.001mol) 2-fluoro-5-amine picoline down.Add the back and rise to room temperature reaction naturally, after reaction finishes, precipitation, ethyl acetate: sherwood oil=1: 2 column chromatography obtains white solid 0.21 gram, productive rate 95.47%.
Synthesizing of embodiment 11 2-cyano group-3-ethyl-3-(2 '-fluoro-5 '-pyridine) methylamino-vinylformic acid ethoxy ethyl ester
In the 100mL four-hole bottle, add 2-cyano group-3-methoxyl group-3-ethylacrylic acid ethoxy ethyl ester of 0.001mol, 10mLTHF, low temperature drip the 10mLTHF solution of the 2-fluoro-5-amine picoline of 0.001mol down.Add the back and rise to room temperature reaction naturally, after reaction finishes, precipitation, ethyl acetate: sherwood oil=1: 2 column chromatography obtains white solid, productive rate 92.35%.
Synthesized compound (I) according to similar method, all compounds are through nuclear-magnetism, and ultimate analysis is proved conclusively.Part of compounds has been done infrared.Concrete outcome sees Table 1
Table 1 compound (I)
Physical properties characterize
| ????No | ??R 1 | ????R 2 | State (mpOC) |
| ????1 | ??-C 2H 5O-m-CH 3-Ph | ????CH 3S- | White solid (70-71) |
| ????2 | ??-C 2H 5O-p-CH 3-Ph | ????CH 3S- | Faint yellow solid (67-68) |
| ????3 | ??-C 2H 5O-o-NO 2-Ph | ????CH 3S- | White solid (99-101) |
| ????4 | ??-C 2H 5O-p-NO 2-Ph | ????CH 3S- | White solid (102-103) |
| ????5 | ??-C 2H 5O-m-OCH 3-Ph | ????CH 3S- | White solid (80-82) |
| ????6 | ??-C 2H 5O-2，4-2Cl-Ph | ????CH 3S- | Yellow solid |
| ????7 | ??-C 2H 5O-o-CF 3-Ph | ????CH 3S- | Yellow solid (68-69) |
| ????8 | ??-C 2H 5O-2.4-2CH 3，6- ??NO 2-Ph | ????CH 3S- | Yellow solid (154-156) |
| ????9 | ??-C 2H 5O-Ph | ????CH 3S- | Yellow liquid |
| ????10 | ??-C 2H 5O-o-CH 3-Ph | ????CH 3S- | Yellow liquid |
| ????11 | ??-C 2H 5O-m-NO 2-Ph | ????CH 3S- | White solid (114-115) |
| ????12 | ????-C 2H 5O-o-Cl-Ph | ????CH 3S- | Faint yellow solid (81-82) |
| ????13 | ????-C 2H 5O-C 2H 5 | ????CH 3S- | White solid (50-51) |
| ????14 | ????CN | ????CH 3S- | White solid (115-116) |
| ????15 | ????CO 2C 2H 5 | ????CH 3S- | Faint yellow solid (95-96) |
| ????16 | ????CO 2C 2H 5 | ????PhCH 2S- | Faint yellow solid |
| ????17 | ????CN | ????PhCH 2S- | Yellow liquid |
| ????18 | ????-C 2H 5O-C 2H 5 | ????C 2H 5- | Yellow liquid |
| ????19 | ????-C 2H 5O-C 2H 5 | ????i-Pr- | Yellow liquid |
Table 2 compound (1)
1HNMR composes data
| ????No.(Sol.) | ? 1H?NMR(δ，ppm) |
| ????1?CDCl 3 | ?2.213(s，3H，CH 3)，2.697(s，3H，SCH 3)，4.205-4.237(t，2H，OCH 2，)，4. ?521-4.553(t，2H，COOCH 2),4.782-4.802(d，2H，NHCH 2)，6.810-8.1 ?67(m，7H，CH?ofpyridinyl?and?Ph)，10.345(w，1H，NH) |
| ????2?CDCl 3 | ?2.283(s，3H，CH 3)，2.700(s，3H，SCH 3)，4.182-4.216(t，2H，OCH 2，)，4. ?475-4.507(t，2H，COOCH 2)，4.781-4.801(d，2H，NHCH 2)，6.805-8.6 ?15(m，7H，CH?ofpyridinyl?and?Ph)，10.335(w，1H，NH) |
| ????3?CDCl 3 | ?2.709(s，3H，SCH 3)，4.119-4.231(t，2H，OCH 2，)，4.487-4.519(1，2H，C ?OOCH 2)，4.792-4.812(d，2H，NHCH 2)，6.809-8.179(m，7H，CHof ?pyrdinyl?and?Ph)10.331(w，1H，NH) |
| ????4?CDCl 3 | ?2.702(s，3H，SCH 3)，4.196(t，2H，OCH 2，)，4.490(s，2H，COOCH 2)，4.7 ?83-4.803(s，2H，NHCH 2)，6.794-8.169(m，7H，CHof?pyridinyl?and ?Ph)10.317(w，1H，NH) |
| ????5?CDCl 3 | ?2.708(s，3H，SCH 3)，3.859(s，3H，OCH 3)，4.287-4313(t，2H，OCH 2)， ?4.509-4.545(t.2H，COOCH 2)，4.783-4.803(d，2H，NHCH 2)，6.887-8 ?.169(m，7H，CHof?pyridinyl?and?Ph)10.331(w，1H，NH) |
| ????6?CDCl 3 | ?2.700(s，3H，SCH 3)，3.859(s，3H，OCH 3)，4.279(s，2H，OCH 2)， ?4.543(s，2H，COOCH 2)，4.788-4.806(d，2H，NHCH 2)，6.930-8.171( ?m，6H，CH?of?pyridinyl?and?Ph)10.322(w，1H，NH) |
| ????7?CDCl 3 | ?2.708(s，3H，SCH 3)，4.249-4.287(t，2H，OCH 2，)，4.511-4.543(t，2H，C ?OOCH 2)，4.791-4.812(d，2H，NHCH 2)，6.966-8.176(m，7H，CHof ?pyridinyl?and?Ph)10.330(w，1H，NH) |
| ????8?CDCl 3 | ?2.248(s，3H，CH 3)，2.342(s，3H，CH 3)，2.699(s，3H，SCH 3)，4.271(s，2 ?H，OCH 2，)，4.517(s，2H，COOCH 2)，4.813-4.831(d，2H，NHCH 2)，6.6 ?76-8.190(m，7H，CHof?pyridinyl?and?Ph)10.294(w，1H，NH) |
| ????9?CDCl 3 | ?2.698(s，3H，SCH 3)，4.228(s，2H，OCH 2，)，4.509(s，2H，COOCH 2)，4.7 ?8333-4.802(d，2H，NHCH 2)，6.906-8.169(m，8H，CHofpyridinyland ?Ph)，10.338(w，1H，NH) |
| ????10?CDCl 3 | ?2.323(s，3H，CH 3)2.698(s，3H，SCH 3)，4.211(s，2H，OCH 2，)，4.498(s，2 ?H，COOCH 2)，4.784-4.804(d，2H，NHCH 2)，6.707-8.171(m，7H，CH ?of?pyridinyl?and?Ph)，10.336(w，1H，NH) |
| ????11?CDCl 3 | ?2.811(s，3H，SCH 3)，4.486-4.517(t，2H，OCH 2，)，4.701-4.732(t，2H，C ?OOCH 2)，4.933-4.952(d，2H，NHCH 2)，7.107-8.309(m，7H，CHof ?pyridinyl?and?Ph)，10.438(w，1H，NH) |
| ????12?CDCl 3 | ?2.706(s，3H，SCH 3)，4.199-4.231(t，2H，OCH 2，)，4.487-4.519(t，2H，C ?OOCH 2)，4.792-4.812(d，2H，NHCH 2)，6.809-8.179(m，7H，CHofpy ?ridinylandPh)，10.331(w，1H，NH) |
| ????13?CDCl 3 | ?1.174-1.222(t，3H，OCH 2CH 3)，2.687(s，3H，SCH 3)，3.524-3.594(q， ?2H，OCH 2CH 3)，3.666-3.702(t，2H，COOCH 2CH 2O)，4.269-4.304(t， ?2H，COOCH 2CH 2O)，4.776-4.796(d，2H，NHCH 2)，6.961-8.161(m， ?7H，CHof?pyridinyl?and?Ph)，10.343(w，1H，NH) |
| ????14?CDCl 3 | ?2.625(s，3H，SCH 3)，4.486-4.517(t，2H，OCH 2)，4.648-4.668(d，2H，N ?HCH 2)，6.912-8.120(m，3H，CHofpyridinyl) |
| ????15?CDCl 3 | ?1.226-1.275(t，3H，CH 2CH 3)，2.620(s，3H，SCH 3)，4.486-4.517(t，2H， ?OCH 2)，4.112-4.182(q，2H，CH 2CH 3)，4.714-4.734(d，2H，NHCH 2)， ?6.889-8.101(m，3H，CHofpyridinyl)，10.325(w，1H，NH) |
| ????16?CDCl 3 | ?1.318-1.365(t，3H，CH 2CH 3)，4.112-4.182(q，2H，CH 2CH 3)，4.383(s， ?2H，SCH 2Ph)，4.508-4.526(d，2H，NHCH 2)，6.846-7.935(m，8H，CH ?of?pyridinyl?and?Ph)，10.266(w，1H，NH) |
| ????17?CDCl 3 | ?4.353(s，2H，SCH 2Ph)，4.541-4.556(d，2H，NHCH 2)，6.889-7.994(m， ?8H，CHof?pyridinyl?and?Ph) |
| ????18?CDCl 3 | ?1.185-1.233(t，3H，CH 2CH 3)，1.260-1.311(t，3H，OCH 2CH 3)，2.623- ?2.702(q，2H，CH 2CH 3)，3.535-3.605(q，2H，OCH 2CH 3)，3.673-3.705 ?(t，2H，COOCH 2CH 2O)，4.265-4.298(t，2H，COOCH 2CH 2O)，4.560- ?4.581(d，2H，NHCH 2)，6.969-8.161(m，3H，CHofpyridinyl)，10.168( ?w，1H，NH) |
| ????19?CDCl 3 | ?1.187-1.235(m，4H，OCH 2CH 3，CH(CH 3) 2)，1.386-1.408(d，6H，CH( ?CH 3) 2)，3.542-3.613(q，2H，OCH 2CH 3)，3.680-3.713(t，2H，COOCH ? 2CH 2O)，4.280-4.316(t，2H，COOCH 2CH 2O)，4.612-4.631(d，2H，N ?HCH 2)，6.941-8.201(m，3H，CHofpyridinyl)，10.567(w，1H，NH) |
The primary dcreening operation of embodiment 12 weeding activity is measured
Pot-culture method (cauline leaf processing): put into a certain amount of soil in the plastics cuvette of diameter 8cm, add a certain amount of water, after planting cover certain thickness soil, cultivate in greenhouse, it is preceding with plastic covered to come up.After emerging, every day in addition quantitative clear water to keep normal growth.Carrying out the cauline leaf spraying when seedling length to the certain period handles.Treatment dosage is a 100g/ mu.Handle 10 days " Invest, Then Investigate " results, measure the overground part fresh weight, suppress percentage ratio with fresh weight and represent drug effect.
Pot-culture method (soil treatment): put into a certain amount of soil in the plastics cuvette of diameter 8cm, add a certain amount of water, after planting cover certain thickness soil, and in dispenser on the same day, cultivate in greenhouse then, it is preceding with plastic covered to come up.After emerging, every day in addition quantitative clear water to keep normal growth.Carrying out the cauline leaf spraying when seedling length to the certain period handles.Treatment dosage is a 100g/ mu.Handle 10 days " Invest, Then Investigate " results, measure the overground part fresh weight, suppress percentage ratio with fresh weight and represent drug effect.
Table 3: the weeding activity inhibiting rate (%) of part of compounds (I) (dosage 100 gram/mus)
| Numbering | Rape | The barnyard grass grass | ||
| Cauline leaf is handled | Soil treatment | Cauline leaf is handled | Soil treatment | |
| ????1 | ????96.0 | ????19.9 | ????43.8 | ????0 |
| ????2 | ????52.0 | ????54.8 | ????14.6 | ????7.9 |
| ????4 | ????31.2 | ????23.7 | ????1.1 | ????6.9 |
| ????5 | ????89.6 | ????12.9 | ????58.2 | ????12.2 |
| ????6 | ????72.8 | ????19.9 | ????22.0 | ????7.9 |
| ????7 | ????100 | ????20.4 | ????29.0 | ????18.0 |
| ????8 | ????41.6 | ????18.3 | ????9.8 | ????5.8 |
| ????9 | ????100 | ????43.5 | ????69.5 | ????59.8 |
| ????10 | ????100 | ????27.4 | ????68.6 | ????29.6 |
| ????12 | ????100 | ????27.4 | ????56.9 | ????3.7 |
| ????13 | ????100 | ????89.2 | ????96.9 | ????69.8 |
| ????14 | ????18.8 | ????16.1 | ????7.2 | ????66.1 |
| ????15 | ????93.6 | ????66.1 | ????42.0 | ????36.0 |
| ????16 | ????37.1 | ????28.5 | ????0 | ????55.6 |
| ????17 | ????5.4 | ????39.2 | ????8.1 | ????33.3 |
| ????18 | ????100 | ????80.1 | ????95.6 | ????70.9 |
| ????19 | ????100 | ????88.2 | ????97.6 | ????68.6 |
The multiple sieve of embodiment 13. weeding activity is measured
Allowing 13,18,19 reduction dosage carry out multiple sieve to the outstanding compound of activity measures.Measuring method the results are shown in Table 4 with embodiment 12: the weeding activity of part of compounds (I) sieves result (inhibiting rate %) again
Table 4: the weeding activity inhibiting rate (%) of part of compounds (I) (dosage 12.5 gram/mus)
| Numbering | Rape | The barnyard grass grass | ||
| Cauline leaf is handled | Soil treatment | Cauline leaf is handled | Soil treatment | |
| ????13 | ????100 | ????87.2 | ????93.9 | ????39.8 |
| ????18 | ????100 | ????78.9 | ????93.6 | ????32.9 |
| ????19 | ????100 | ????88.2 | ????92.6 | ????24.3 |
Claims (5)
1, a kind of cyanoacrylate compound of fluorinated pyridine methylamino-is characterized in that it is that general formula is the compound of (I):
Wherein, R
1Be alkyl, alkoxyalkyl, aryloxyalkyl group, alcoxyl alkoxyalkyl, fragrant oxygen aryloxyalkyl group; R
2Be alkyl or alkylthio.
2,, it is characterized in that said alkyl is C according to the cyanoacrylate compound of the said fluorinated pyridine methylamino-of claim 1
1-C
6Alkyl.
3, according to the cyanoacrylate compound of claim 1 or 2 said fluorinated pyridine methylamino-s, it is characterized in that said R
1Be-C
2H
5O-m-CH
3-Ph ,-C
2H
5O-m-NO
2-Ph ,-C
2H
5O-m-NO
2-Ph ,-C
2H
5O-m-OCH
3-Ph ,-C
2H
5O-2,4-2Cl-Ph ,-C
2H
5O-o-CF
3-Ph ,-C
2H
5O-2,4-2CH
3, 6-NO
2-Ph ,-C
2H
5O-Ph ,-C
2H
5O-o-Cl-Ph ,-C
2H
5O-C
2H
5, CN or CO
2C
2H
5, R
2Be CH
3S-, PhCH
2S-, C
2H
5-or i-Pr-.
4,, it is characterized in that it is through following step according to the preparation method of the cyanoacrylate compound of the said fluorinated pyridine methylamino-of claim 1:
(1) with cyan-acetic ester or propane dinitrile and dithiocarbonic anhydride, sodium hydroxide or potassium hydroxide, wherein mol ratio is 1: 1: 2-2.1, put into dioxane, anhydrous acetonitrile or anhydrous ethanol solvent, and reacted 0.5-3 hour down at 0-40 ℃; Add haloalkane or methyl-sulfate at 0-40 ℃, mol ratio is 1: 2-2.1, reacted 6-10 hour down in 0-40 ℃; Ice bath is separated out solid, or the adding elutriation goes out oily matter in reaction system, is intermediate 3,3-two alkylthio acrylate or vinyl cyanide;
(2) cyan-acetic ester or propane dinitrile and former propionic acid trimethyl or trimethyl orthoacetate or former isopropylformic acid trimethyl, mol ratio is 1: 1-1.5, in diacetyl oxide, being heated to 100～140 ℃ reacts after 1-2 hour down, steam lower boiling material, the question response system temperature is raised to 130-140 ℃, continuation was this temperature range reaction 1-2 hour, steam lower boiling material again, the question response system temperature is raised to 130-140 ℃ and continues reaction, arrive 140 ℃ up to the reflux temperature of reaction system, and keep constantly, continued back flow reaction 1-2 hour, cool to room temperature, the sherwood oil that adds 60-90 ℃ in reaction system stirs and separates out solid, filter intermediate 2-cyano group-3-methoxyl group-3 '-alkyl acrylate or vinyl cyanide;
(3) add 2-fluoro-5-cyanopyridine in autoclave, with the saturated ethanol solution of ammonia, Raney Ni is at 15-100atm H
2, carry out reduction reaction under 20-80 ℃, reaction removes by filter Raney Ni after finishing, and the filtrate carrying out precipitation treatment is removed ethanol and ammonia, and 74-76 ℃/3-5mmHg cut is collected in the residue underpressure distillation, obtains 2-fluoro-5-aminomethyl-pyridine;
(4) make 3,3-two alkylthio acrylate or vinyl cyanide and 2-fluoro-5-pyridyl-methanamine, mol ratio is 1: 1.1～1.2, reacts in tetrahydrofuran (THF) or chloroform, alcoholic acid solvent, refluxes 8～12 hours, concentrates; As obtain solid, get final product with ethyl acetate-sherwood oil recrystallization; If obtain oily matter, separate purification with rapid column chromatography, can obtain final product;
(5) make 3 '-alkyl-3-alkoxy acrylic ester or vinyl cyanide and 2-fluoro-5-pyridyl-methanamine, mol ratio is 1: 1.1～1.2, reacts in tetrahydrofuran (THF) or chloroform, alcoholic acid equal solvent, refluxes about 12 hours, concentrates; As obtain solid, get final product with ethyl acetate-sherwood oil recrystallization; If obtain oily matter, separate purification with rapid column chromatography, can obtain final product.
5, the application of the cyanoacrylate compound of the described fluorinated pyridine methylamino-of claim 1 is characterized in that the weedicide as the rape in the corn field, Amaranthus retroflexus broadleaf weeds, barnyard grass grass or lady's-grass gramineous weeds.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410019757 CN1286813C (en) | 2004-06-28 | 2004-06-28 | Cyanoacrylate compounds containing fluoro pyridine-methylamino group and their bioactivity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410019757 CN1286813C (en) | 2004-06-28 | 2004-06-28 | Cyanoacrylate compounds containing fluoro pyridine-methylamino group and their bioactivity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1594294A true CN1594294A (en) | 2005-03-16 |
| CN1286813C CN1286813C (en) | 2006-11-29 |
Family
ID=34663079
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410019757 Expired - Fee Related CN1286813C (en) | 2004-06-28 | 2004-06-28 | Cyanoacrylate compounds containing fluoro pyridine-methylamino group and their bioactivity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1286813C (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101659636A (en) * | 2009-03-24 | 2010-03-03 | 南开大学 | Synthesis and herbicidal activity of 2-cyano-3-alkoxy-3'-methyl acrylic acid ester |
| CN102952066A (en) * | 2011-08-30 | 2013-03-06 | 南开大学 | Synthesis and biological activity of cyanoacrylate compound containing pyridylmethyl phenyl ether structure |
-
2004
- 2004-06-28 CN CN 200410019757 patent/CN1286813C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101659636A (en) * | 2009-03-24 | 2010-03-03 | 南开大学 | Synthesis and herbicidal activity of 2-cyano-3-alkoxy-3'-methyl acrylic acid ester |
| CN101659636B (en) * | 2009-03-24 | 2014-01-15 | 南开大学 | Synthesis and herbicidal activity of 2-cyano-3-alkoxy-3'-methyl acrylic acid ester |
| CN102952066A (en) * | 2011-08-30 | 2013-03-06 | 南开大学 | Synthesis and biological activity of cyanoacrylate compound containing pyridylmethyl phenyl ether structure |
| CN102952066B (en) * | 2011-08-30 | 2014-06-04 | 南开大学 | Synthesis and biological activity of cyanoacrylate compound containing pyridylmethyl phenyl ether structure |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1286813C (en) | 2006-11-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101279950B (en) | 2-pyrimindinyloxy (pyrimindinylthio) benzoxy acetamide compound and application thereof | |
| CN1066440C (en) | Preparing method for 4-benzoyl isooxazole derivative | |
| CZ9489A3 (en) | Heterocyclically substituted alkylene quinolinyloxyphenoxypropenoates, herbicides containing such substance and process for suppression of undesired plant growth | |
| CN1286813C (en) | Cyanoacrylate compounds containing fluoro pyridine-methylamino group and their bioactivity | |
| CN1194975C (en) | Helerocyclic substituted benzoxazine cyclic compound having biological activity | |
| CN108191755B (en) | Herbicides compounds and its preparation method and application | |
| CN1129936A (en) | Substituted 1-amino-3-phenyluracils with berbicidal activities | |
| CN1239403A (en) | Herbicidal compsn. | |
| CN103012289B (en) | Synthesis and biological activity of cyanoacrylate compound containing pyrimidine phenylate structure | |
| CN114957166B (en) | Phenylacetamide compound and preparation method and application thereof | |
| KR910008476B1 (en) | Process for fungicidal pyridazines | |
| CN102952066B (en) | Synthesis and biological activity of cyanoacrylate compound containing pyridylmethyl phenyl ether structure | |
| CN1246474A (en) | Cyanoacrylate compounds containing sulfenyl pyridinemethanamine group and its bioactivity | |
| CN102883599B (en) | For reducing the isomerized UV absorbent of agricultural chemicals E/Z | |
| JPS6072871A (en) | N-substituted-5-(substituted phenyl)-1,3- oxazolidine and herbicidal detoxicant | |
| CN1309303C (en) | Herbicide used in rape field, prepn. method and use thereof | |
| CN1106393A (en) | Sulfonylurea compound herbicide | |
| CN101747202B (en) | 2-chloro-benzoate compound and application thereof | |
| CN1927843A (en) | Compound of 2-substituted alkylacrylate and application thereof | |
| CN1233618C (en) | Benzoylcyclohexanone amine compounds with herbicidal activity | |
| CN1233623C (en) | 2,6-dibromo-4-cyanophenyl ester compounds with herbicidal activity | |
| CN1289493C (en) | Compound of dibenzanthracene-1,3-dioxa-cyclooctane-2-amide class of possessing weeding activity | |
| JPH01250363A (en) | 4-benzylaminopyrimidine derivative and herbicide | |
| CN1033551C (en) | Thiadiazabicyciononane derivatives and herbicidal compositions | |
| CN116589430A (en) | Fluorine-containing amide thiazolidine ester compound and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |