CN107903265A - A kind of preparation method and application of New-type spiro insecticides - Google Patents
A kind of preparation method and application of New-type spiro insecticides Download PDFInfo
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- CN107903265A CN107903265A CN201711166015.5A CN201711166015A CN107903265A CN 107903265 A CN107903265 A CN 107903265A CN 201711166015 A CN201711166015 A CN 201711166015A CN 107903265 A CN107903265 A CN 107903265A
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
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Abstract
The invention discloses a kind of preparation method and application of New-type spiro insecticides, belong to pesticide synthesis technical field.Technical key point is：
Description
Technical field
The invention belongs to pesticide synthesis technical field, and in particular to a kind of preparation method of New-type spiro insecticides and should
With.
Background technology
With the fast development of social economy and the continuous improvement of living standards of the people, food-safety problem becomes people increasingly
Focus of attention.Therefore, in the development process of new varieties of pesticides, emphasize more to pay attention to the phase of environment while high activity
Capacitive, to ensure the safety of the mankind and non-target organism.Similar insect conditioning agent and loop coil class desinsection with optical activation
Agent, is exactly the environment friendly agricultural that people usually say.The mankind are to the requirements at the higher level of pesticide, and the resistance problem and science of pesticide itself
The continuous development of technology, requires that pesticide will constantly bring forth new ideas.It is excellent that New pesticides discovery is related to MOLECULE DESIGN, synthesis, screening, structure
Change and derivative, determination of activity, field control effectiveness test and its popularization, process exploitation, safety and environmental evaluation and registration etc.
All too many levels, are a system engineerings that professional span is big, subject crossing is strong.The MOLECULE DESIGN of lead compound and synthesis are
The core link of initiative, and wherein MOLECULE DESIGN link be can be successful key, thus reasonable design and synthesize
Pilot compound is the difficult point that New pesticides discovery researcher faces.In mentality of designing, the initiative of novel pesticide is just like issuing
Open up direction：1st, heterocyclic pesticide is the mainstream of novel pesticide development；2nd, racemic pesticide develops to single chiral body；3rd, in compound
New element is introduced in structure；4th, the pesticide molecule design based on physiological and biochemical procedure；5th, the research and development of biogenic pesticide；6、
Applications of the QSAR in pesticide molecule design.The initiative of current novel pesticide mainly has four kinds of approach：Random synthesis screening, similar conjunction
Cheng Fa, natural active matter modelling and biorational design method.Wherein screened with random synthesis with being synthesized mainly with similar
Approach.
Contain one or more spirane structures in loop coil insecticides molecule, be the new lover in the field, foreign countries are present energetically
Develop and use this insecticide and pesticide.And domestic also this structure of utilization not yet in effect, therefore Devoting Major Efforts To Developing and spy at this stage
Its synthesis route of rope is necessary.Two plane of a loops of spiro-compound are mutually perpendicular to, for heterocyclic ring spiroring chemical combination
Thing may also have the special nature that the general organic compound such as different head effect, spiral shell conjugation, spiral shell hyperconjugation does not possess, due to chirality
The presence of axis, under certain conditions, can be into asymmetric molecult or chiral molecular；Chiral spiro is rigidly strong, is not easy racemization
Change.It is unique containing the heteroatomic spiro-compound mechanism of action, the resistance to the action of a drug is not likely to produce, has caused the concern of common people.
Spiral shell worm ethyl ester is one and represents molecule in loop coil insecticides molecule.It is the tetronic acid class developed by Beyer Co., Ltd
Desinsection kills snail agent.Formulation is mainly the suspending agent of 240g/L.It is mainly used for cotton, vegetables and ornamental plant prevention aleyrodid and leaf
Mite.The property of compound is that its ovum and adult to aleyrodid class and snail class is all effective, especially red to room temperature aleyrodid and cotton
Spider.With 100~150g/hm2Dosage be used for cotton, vegetables and ornamental plant, the very long lasting period can be kept；In grass
Good application prospect is also showed that on the orchard crops such as the certain kind of berries, apple and seeding corn and other crops.If it is worth noting that, it is to aleyrodid
Worm and deutonymph are especially effective, also there is high lethality to aleyrodid ovum.The incubation rate of ovum can be also reduced, it is very high except having to its adult
Outside preventive effect, its spawning rate can be also reduced.If it is coordinated to the deficiency for making up its early prevention and treatment with imidacloprid.Applying
On, really one " tolerance " very high kind, new construction introduce new capability for it.We carry out in the structure of spiral shell worm ethyl ester
Optimization, using the benzene ring structure replaced with extensive insecticidal activity oxazole rings in spiral shell worm ethyl ester, finds obtained new
Compound has good killing activity to some plant insects.
The content of the invention
The technical problem to be solved by the present invention is to provide one kind, operation is simple, raw material is cheap and easy to get, compound structure
Novelty, insecticidal activity is good, reaction efficiency is high and a kind of synthetic method of reproducible New-type spiro insecticides.
The present invention is to solve above-mentioned technical problem to adopt the following technical scheme that, a kind of Cheng Fang of New-type spiro insecticides
Method, it is characterised in that concretely comprise the following steps：
A, pyridone and dimethyl suflfate and methanol are reacted to obtain N- methoxyl group -4- pyridones；
B, N- methoxyl groups -4- pyridones obtain N- methoxyl groups -4-aminopyridine with ammonia generation substitution reaction；
C, N- methoxyl groups -4-aminopyridine occurs annulation in nonpolar solvent with formamide and carbon monoxide and obtains
Cis-8- methoxyl group -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone；
D, cis-8- methoxyl groups -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone hydrolyzes to obtain in alkaline conditions
Cis-4- amino -1- methoxypyridine -4- formic acid；
E, cis-4- amino -1- methoxypyridine -4- formic acid obtains cis-4- amino -1- first with methanol generation esterification
Epoxide pyridine-4-formic acid methyl esters；
F, with 2,5- dimethyl benzenes chloroacetic chloride substitution reaction occurs for cis-4- amino -1- methoxypyridine -4- methyl formates
Self-condensation occurs again in alkaline conditions afterwards and obtains cis-3- (2,5- 3,5-dimethylphenyls) -8- methoxyl group -2- oxos -1,8- two
Azaspiro [4,5] decyl- 3- alkene -4- alcohol；
G, cis-3- (2,5- 3,5-dimethylphenyls) -8- methoxyl group -2- oxo -1,8- diazaspiracyclics [4,5] decyl- 3- alkene -
4- alcohol reacts to obtain with hydrazine hydrate
Further limit, the detailed process of step A：Added in reaction bulb to pyridone, methanol and dimethyl suflfate,
60 DEG C are warming up to after reacting 2h at ambient temperature, the reaction was continued a period of time, and the reaction was complete for TLC monitoring raw material, is cooled to 0
DEG C, it is slowly added dropwise saturated sodium bicarbonate solution, adjusts reaction solution pH as neutrality, then with chloroform extractive reaction liquid, merges organic phase
After be concentrated to give N- methoxyl group -4- pyridones.
Further limit, the detailed process of step B：N- methoxyl group -4- pyridones and triphenyl are added in reaction bulb
Ammonium hydroxide is slowly added dropwise as solvent in phosphine, pyridine, reacts 5h after dripping at ambient temperature, and the reaction was complete for TLC monitoring raw material,
Filtering reacting liquid, with chloroform extractive reaction liquid, N- methoxyl groups -4-aminopyridine is concentrated to give after merging organic phase.
Further limit, the detailed process of step C：Nonpolar solvent is added into autoclave, opens stirring, is added
Formamide, adds N- methoxyl groups -4-aminopyridine, CO is passed through into reaction kettle, pressure in kettle is reached 0.2MPa after stirring, rise
Temperature to 50 DEG C of reaction a period of times, middle control raw material is less than 2%, and reaction terminates, and is cooled to 25~30 DEG C, is added dropwise into reaction solution dilute
Hydrochloric acid, it is 5~6 to adjust pH, has solid precipitation, filters out product, filter cake shuffles once, obtains cis-8- methoxyl groups -1,3,8- tri-
Azaspiro [4,5]-decyl- 2,4- diketone；The nonpolar solvent is hexamethylene, hexahydrotoluene, ethyl cyclohexane, chloro ring
Hexane, preferably ethyl cyclohexane.
Further limit, the detailed process of step D：Water is added into reaction bulb, 40 DEG C or so are heated under stirring, hydrogen
In barium monoxide input four-hole bottle, stirring and dissolving；Addition cis-8- methoxyl groups -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone,
Be heated to back flow reaction 5 it is small when；Sampling monitoring, stops reaction after starting material left amount area percentage composition is less than 2%, has reacted
Cheng Hou, cools down 60 DEG C or so, and the concentrated sulfuric acid is slowly added dropwise into four-hole bottle, adjusts pH value 3 or so；10min repetition measurement pH value is stirred, surely
Water and activated carbon are added in fixed backward system, 80 DEG C is warming up to and stirs 60 minutes；It is residue to filter out solid while hot, and filtrate is heated
Concentrate, concentrate water unnecessary in system under vacuum condition, when steaming to thick-pasty, distillation terminates to add toluene, (for being dehydrated
Toluene can reuse 3 times, when each reuse adds one barrel of new toluene) normal pressure divides water, after moisture to the greatest extent after, be cooled to less than 30 DEG C；
Centrifugal filtration, solid drying are weighed up to cis-4- amino -1- methoxypyridine -4- formic acid.
Further limit, the detailed process of step E：Methanol is added into reaction bulb, stirs lower addition cis-4- amino -1-
Methoxypyridine -4- formic acid, is stirred 10 minutes；(excessive 1.2mol) thionyl chloride is slowly added dropwise, time for adding is about 2~3 small
When；Process control kettle temperature is added dropwise and is less than 60 DEG C, is suitable with visible micro- reflux on condenser；It is added dropwise, it is anti-is warming up to reflux
Answer 10 it is small when, sampling detection；Detect after reaction raw materials surplus area percentage composition is less than 1% and stop reaction；Vacuum removal is molten
Agent methanol, steams to thick, stopping heating；Hexamethylene is added into reaction bulb, atmospheric pressure reflux separates remaining methanol in system
(water knockout drum lower floor is methanol)；When can't see methanol and separate, stop reaction；Cooling water temperature is opened to less than 30 DEG C, mistake
Filter to obtain cis-4- amino -1- methoxypyridine -4- methyl formates.
Further limit, the detailed process of step F：DMF is added into reaction bulb, stirs lower addition cis-4- amino -1-
Methoxypyridine -4- methyl formates, are slow added into sodium acid carbonate, great amount of carbon dioxide can be released, it is necessary to control in adition process
Make and add speed, (when adding 30% or so of total carbonic acid hydrogen sodium amount, can accelerate to add speed, do not have foam effusion) adds
Stirring 30 minutes after complete；Ethyl acetate is added, is put into ice-water bath, reaction solution is cooled to 0 DEG C；Start that 2,5- dimethyl is added dropwise
Phenyllacetyl chloride, controls 0~5 DEG C of temperature, and rate of addition is controlled with temperature；After being added dropwise, when 0~5 DEG C of stirring reaction 5 is small,
Sampling monitoring reaction process, when starting material left is less than 2%, reaction terminates；Add KF/Al2O3, open stirring；And it is passed through nitrogen
There is bubble to emerge to bubbler.20~30 DEG C of kettle temperature and nitrogen protection are controlled, when this temperature stirring reaction 2 is small, sampling detection,
Raw material area percentage content stops reaction after being less than 0.5%；Vacuum is opened to -0.1Mpa, 80~90 DEG C of kettle temperature, is removed under decompression
Neat solvent is waited to steam to thick-pasty, after being cooled to 40 DEG C, opens nitrogen protection, and water is added dropwise into system and (notices that phenomenon becomes in kettle
Change and temperature change) after completion of dropwise addition, stir 15min, remaining water is disposably added after stablizing, being slow added into concentration is
20min is stirred after 6% NaOH solution, filters out KF/Al2O3(repeatable to utilize), static layering, upper strata floccule point falls to abandon
Go, lower aqueous layer retains, and hydrochloric acid acidifying is added dropwise, and (acid adding speed needs to control, and too fast addition speed can make the moment that product separates out
Parcel impurity and form lump) there are in kettle a large amount of solids to separate out, when pH value reaches 3~4, continue to filter after stirring a period of time
Go out solid product and obtain cis-3- (2,5- 3,5-dimethylphenyls) -8- methoxyl group -2- oxo -1,8- diazaspiracyclics [4,5] decyl- 3-
Alkene -4- alcohol.
Further limit, the detailed process of step G：DMSO is added into reaction bulb；Add and do into bottle under stirring
Dry cis-3- (2,5- 3,5-dimethylphenyls) -8- methoxyl group -2- oxo -1,8- diazaspiracyclics [4,5] decyl- 3- alkene -4- alcohol；Stir
Hydrazine hydrate is slowly added to after mixing, addition finishes adjustment temperature to 150 DEG C；Reacted under air atmosphere, when starting material left is small
React and terminate when 1%；A certain amount of water is added into reaction bulb；Stirring adds a certain amount of chloroform extractive reaction after twenty minutes
Liquid, extraction merge organic phase afterwards three times, and concentration organic phase is isolated through silica gel column chromatography
The synthetic route of New-type spiro insecticides of the present invention is：
Operation is simple, raw material is cheap and easy to get, reaction efficiency is high and reproducible for present invention kind.
Embodiment
The above of the present invention is described in further details by the following examples, but this should not be interpreted as to this
The scope for inventing above-mentioned theme is only limitted to following embodiment, and all technologies realized based on the above of the present invention belong to this hair
Bright scope.
Embodiment 1
Added in reaction bulb to pyridone 100g (1mol) and dimethyl suflfate 126g (1mol), add methanol
100mL, 60 DEG C are warming up to after reacting 2h at ambient temperature, the reaction was continued 3h, and the reaction was complete for TLC monitoring raw material, is cooled to 0
DEG C, it is slowly added dropwise saturated sodium bicarbonate solution, adjusts reaction solution pH as neutrality, then with chloroform extractive reaction liquid, merges organic phase
After be concentrated to give N- methoxyl group -4- pyridones.
Embodiment 2
N- methoxyl group -4- pyridones 13g (0.1mol) are added in reaction bulb and triphenylphosphine 7g, pyridine 200mL make
For solvent, the ammonium hydroxide 20g that concentration is 25% is slowly added dropwise after stirring evenly under the conditions of 0 DEG C, after dripping at ambient temperature
5h is reacted, the reaction was complete for TLC monitoring raw material, and filtering reacting liquid, with chloroform extractive reaction liquid, N- is concentrated to give after merging organic phase
Methoxyl group -4-aminopyridine 11g, yield 84.6%.
Embodiment 3
Hexamethylene 1200mL is added into autoclave, opens stirring, addition concentration is 40% formamide solution 225g
(2mol), after stirring 10min, adds N- methoxyl groups -4-aminopyridine 130g (1mol), CO is passed through into reaction kettle, is made in kettle
Pressure reaches 0.2MPa, is warming up to 50 DEG C, keeps the temperature 20h, and middle control raw material is less than 2%, and reaction terminates, and is cooled to 25~30 DEG C, to
Dilute hydrochloric acid is added dropwise in reaction solution, it is 5~6 to adjust pH, has solid precipitation, filters out product, filter cake shuffles once, obtains cis-8- first
Oxy-1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone 112g, yield 56%, is that accessory substance is mainly unreacted after testing
Complete raw material；1HNMR(400MHz,DMSO-d6)δ:10.14(s,1H),6.31(s,1H),3.75(s,3H),3.29-3.25(m,
4H),2.44-2.41(m,4H)。
Embodiment 4
Hexahydrotoluene 1200mL is added into autoclave, opens stirring, addition concentration is 40% formamide solution
225g (2mol), after stirring 10min, adds N- methoxyl groups -4-aminopyridine 130g (1mol), CO is passed through into reaction kettle, is made
Pressure reaches 0.2MPa in kettle, is warming up to 50 DEG C, keeps the temperature 20h, and middle control raw material is less than 2%, and reaction terminates, and is cooled to 25-30 DEG C,
Dilute hydrochloric acid is added dropwise into reaction solution, it is 5~6 to adjust pH, has solid precipitation, filters out product, filter cake shuffles once, obtains cis-8-
Methoxyl group -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone 154g, yield 77%, is that accessory substance is not predominantly anti-after testing
The raw material answered.
Embodiment 5
Ethyl cyclohexane 1200mL is added into autoclave, opens stirring, addition concentration is 40% formamide solution
225g (2mol), after stirring 10min, adds N- methoxyl groups -4-aminopyridine 130g (1mol), CO is passed through into reaction kettle, is made
Pressure reaches 0.2MPa in kettle, is warming up to 50 DEG C, keeps the temperature 20h, and middle control raw material is less than 2%, and reaction terminates, and is cooled to 25-30 DEG C,
Dilute hydrochloric acid is added dropwise into reaction solution, it is 5~6 to adjust pH, has solid precipitation, filters out product, filter cake shuffles once, obtains cis-8-
Methoxyl group -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone dry product 176g, yield 87%, is that accessory substance is mainly after testing
The complete raw material of unreacted.
Embodiment 6
Chlorocyclohexane 1200mL is added into autoclave, opens stirring, addition concentration is 40% formamide solution
225g (2mol), after stirring 10min, adds N- methoxyl groups -4-aminopyridine 130g (1mol), CO is passed through into reaction kettle, is made
Pressure reaches 0.2MPa in kettle, is warming up to 50 DEG C, keeps the temperature 20h, and middle control raw material is less than 2%, and reaction terminates, and is cooled to 25-30 DEG C,
Dilute hydrochloric acid is added dropwise into reaction solution, it is 5~6 to adjust pH, has solid precipitation, filters out product, filter cake shuffles once, obtains cis-8-
Methoxyl group -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone dry product 162g, yield 81%, is that accessory substance is mainly after testing
Chiral isomer.
Embodiment 7
Water 720g is added into 2000L four-hole bottles, 40 DEG C or so are heated under stirring.400g barium hydroxides are put into four mouthfuls
In bottle, stir 10 minutes, dissolving；Add cis-8- methoxyl group -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone 100g
(0.5mol), be heated to back flow reaction 5 it is small when；Sampling monitoring, stops anti-after starting material left amount area percentage composition is less than 2%
Should, after the completion of reaction, cool down 60 DEG C or so, the concentrated sulfuric acid is slowly added dropwise into four-hole bottle, adjust pH value 3 or so；Again into system
Water 150g is added, adds activated carbon 25g afterwards, 80 DEG C is warming up to and stirs 60 minutes；It is residue to filter out solid while hot, and filtrate adds
Thermal concentration, when vacuum reaches -0.1Mpa, water unnecessary in system is fallen in 100 DEG C of concentrations of kettle temperature, when steaming to thick-pasty, distillation is tied
Beam adds toluene 400g, (be used for the toluene that is dehydrated can reuse 3 times, when each reuse adds one barrel of new toluene) normal pressure divides water, treat
After moisture is most, less than 30 DEG C are cooled to；Centrifugal filtration, solid drying are weighed up to cis-4- amino -1- methoxypyridine -4- first
Sour 81g, yield 92%, filtrate for toluene be applied to dehydration (after 3 times, 3 times can be applied mechanically barrelling preserve, treat re-distillation
After be further continued for applying mechanically).
Embodiment 8
Methanol 320mL is added into 1000mL four-hole bottles, stirs lower addition cis-4- amino -1- methoxypyridine -4- first
Sour 80g, is stirred 10 minutes；66g (excessive 1.2mol) thionyl chloride is slowly added dropwise, when time for adding is about 2~3 small；It was added dropwise
Process control kettle temperature is less than 60 DEG C, is suitable with visible micro- reflux on condenser.Be added dropwise, be warming up to back flow reaction 10 it is small when,
Sampling detection；Detect after reaction raw materials surplus area percentage composition is less than 1% and stop reaction；Vacuum extremely -0.08Mpa is opened,
40~60 DEG C of removing solvent methanols, steam to thick, stopping heating；Hexamethylene 400mL, atmospheric pressure reflux point are added into four-hole bottle
Go out remaining methanol in system (water knockout drum lower floor is methanol)；Stop reaction when can't see methanol and separated, open cooling water
Less than 30 DEG C are cooled to, filtering, filtrate recycle to hexamethylene band methanol process, solid is weighed, and obtains cis-4- amino -1- methoxyl groups
Pyridine-4-formic acid methyl esters 95g, yield 92%.
Embodiment 9
Dichloromethane 630g is added into 2000mL four-hole bottles, 2,5- dimethyl benzene second is added from hand hole under stirring
Sour 485g, is stirred 10 minutes；Thionyl chloride 386g is added dropwise into reaction kettle, process is added dropwise and keeps kettle temperature to be less than 40 DEG C, reacted
A large amount of sour gas are produced in journey, tail gas is absorbed with lye；Completion of dropwise addition be warming up to 50 DEG C of back flow reactions 8 it is small when, sampling detection
Raw material area percentage composition stops reaction after being less than 0.5%；If reaction not exclusively continue keep the temperature 1h after sample again in control.Reaction
Still need to not exclusively adding the thionyl chloride of total amount 10%, the reaction was continued, until qualified.After reaction is qualified, normal pressure desolventizing dichloromethane
Alkane, keeps kettle temperature to be no more than 60 DEG C, then vacuumizes -0.08Mpa, steams to not flow liquid, and Liquid Residue is 2,5- dimethyl benzenes in kettle
Chloroacetic chloride, bottling are stand-by；Closed preservation.
Embodiment 10
DMF700g is added into 3000mL four-hole bottles, stirs lower addition cis-4- amino -1- methoxypyridine -4- formic acid
Methyl esters 164g, is slowly added to sodium acid carbonate 154g, great amount of carbon dioxide can be released in adition process afterwards, and particularly preceding 50g adds
It is most obvious, it is necessary to control addition speed to enter process foam, (when adding 30% or so of total carbonic acid hydrogen sodium amount, can accelerate
Enter speed, do not have foam effusion) add after stir 30 minutes；Ethyl acetate 1230g is added, is put into ice-water bath, will react
Liquid is cooled to 0 DEG C；Start that phenyllacetyl chloride 103g is added dropwise, control 0~5 DEG C of temperature, rate of addition is controlled with temperature；It is added dropwise
Afterwards, when 0~5 DEG C of stirring reaction 5 is small, sampling monitoring reaction process, when starting material left is less than 2%, reaction terminates；Add KF/
Al2O3100g, opens stirring；And being passed through nitrogen to bubbler has bubble to emerge；20~30 DEG C of kettle temperature and nitrogen protection are controlled,
When this temperature stirring reaction 2 is small, sampling detection, raw material area percentage content stops reaction after being less than 0.5%；Open vacuum
It is lower except neat solvent is waited to steam to thick-pasty to -0.1Mpa, 80~90 DEG C of kettle temperature, decompression, after being cooled to 40 DEG C, open nitrogen and protect
Shield, (adjustment nitrogen pressure 0.02Mpa) be added dropwise into system water 100g (start 20g to be slowly added dropwise, pays attention in kettle phenomenon change and
Temperature change) after completion of dropwise addition, 15min is stirred, remaining water is disposably added after stablizing, 10min is stirred, is slow added into
The NaOH solution 480g that concentration is 6% stirs 20min after adding, and filters out KF/Al2O3(repeatable to utilize), static layering, on
Layer floccule point falls to discard, and lower aqueous layer retains, and hydrochloric acid acidifying is added dropwise, (acid adding speed needs to control, and too fast addition speed can make
Moment parcel impurity that product separates out and form lump) there are in kettle a large amount of solids to separate out, when pH value reaches 4, acidifying terminates, greatly
Hydrochloric acid 230g is about needed, when pH stable is to 3, continues to stir 30min, filters out solid product afterwards and obtain cis-3- (2,5-
3,5-dimethylphenyl) -8- methoxyl groups -2- oxo -1,8- diazaspiracyclics [4,5] decyl- 3- alkene -4- alcohol 211g, yield 93.4%；1HNMR(400MHz,DMSO-d6)δ:13.86 (s, 1H), 8.55 (s, 1H), 7.13 (d, J=4.0Hz, 1H), 6.74 (d, J=
4.0Hz,1H),3.75(s,3H),3.49-3.46(m,4H),2.40(s,3H),2.25(s,3H),1.66-1.62(m,4H)。
Embodiment 11
DMSO500mL is added into reaction bulb, adds dry cis-3- (2,5- dimethyl benzenes under stirring into bottle
Base) -8- methoxyl groups -2- oxo -1,8- diazaspiracyclics [4,5] decyl- 3- alkene -4- alcohol 60g (0.2mol)；It is slowly added to after stirring
Hydrazine hydrate (0.5mol), addition finish adjustment temperature to 150 DEG C；Reacted under air atmosphere, when starting material left is less than 1%
Shi Fanying terminates；Water 1000mL is added into reaction bulb；Stirring adds chloroform 500mL extractive reactions liquid three times after twenty minutes, closes
And organic phase, concentration organic phase are isolated through silica gel column chromatographyYield is 90%；1HNMR(400MHz,DMSO-d6)δ:8.15 (s, 1H), 7.71 (s, 1H), 6.71 (d, J=4.0Hz, 1H), 6.29 (d, J=
4.0Hz,1H),3.92(s,3H),3.54-3.50(m,4H),2.34(s,3H),2.12(s,3H),1.71-1.69(m,4H)。
Embodiment 12
Insecticidal activity is tested
It is 1 to take 2.5mL volume ratios:The mixed solvent of 1 acetone-methanol is added separately to fill 4mg obtainedMeasuring cup in, stirring makes it fully dissolve, and adds 2.5mL and contains mass fraction for 0.2%
Tween 80 standing tap water, obtain 800mg/L's after stirring evenlySolution 5mL, into one
Step dilution obtains the solution that concentration is 5mg/L.Sprayed using Airbrush spray-on processes.Room temperature aleyrodid and the processing of two-spotted spider mite larva
Observe feeding and death condition day by day afterwards, if test worm eats the feed of chemicals treatment to the greatest extent, supplement untreated fresh feed, 120h
Investigation survival borer population amount afterwards, calculates the death rate.
As can be seen from the above table, the obtained New-type spiro insecticides of the present inventionIt is right
The killing effect of room temperature aleyrodid and two-spotted spider mite larva has reached the level of spiral shell worm ethyl ester.
Basic principle, main features and advantages embodiment above describes the present invention, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe the original of the present invention
Reason, under the scope for not departing from the principle of the invention, various changes and modifications of the present invention are possible, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (10)
1. a kind of New-type spiro insecticides, it is characterised in that its structural formula is：
2. the preparation method of the New-type spiro insecticides described in a kind of claim 1, it is characterised in that concretely comprise the following steps：
A, pyridone and dimethyl suflfate and methanol are reacted to obtain N- methoxyl group -4- pyridones；
B, N- methoxyl groups -4- pyridones obtain N- methoxyl groups -4-aminopyridine with ammonia generation substitution reaction；
C, annulation occurs in nonpolar solvent and obtains cis- with formamide and carbon monoxide for N- methoxyl groups -4-aminopyridine
8- methoxyl group -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone；
D, cis-8- methoxyl groups -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone hydrolyzes to obtain cis-4- in alkaline conditions
Amino -1- methoxypyridine -4- formic acid；
E, cis-4- amino -1- methoxypyridine -4- formic acid obtains cis-4- amino -1- methoxyl groups with methanol generation esterification
Pyridine-4-formic acid methyl esters；
F, cis-4- amino -1- methoxypyridine -4- methyl formates and 2,5- dimethyl benzenes chloroacetic chloride occur after substitution reaction
Self-condensation occurs under alkaline condition again and obtains cis-3- (2,5- 3,5-dimethylphenyls) -8- methoxyl group -2- oxo -1,8- diazas
Loop coil [4,5] decyl- 3- alkene -4- alcohol；
G, cis-3- (2,5- 3,5-dimethylphenyls) -8- methoxyl group -2- oxo -1,8- diazaspiracyclics [4,5] decyl- 3- alkene -4- alcohol
React to obtain with hydrazine hydrate
3. the preparation method of a kind of New-type spiro insecticides according to claim 2, it is characterised in that step A's is specific
Process is：Added in reaction bulb to pyridone, methanol and dimethyl suflfate, 60 are warming up to after reacting 2h at ambient temperature
DEG C, the reaction was continued a period of time, and the reaction was complete for TLC monitoring raw material, is cooled to 0 DEG C, saturated sodium bicarbonate solution is slowly added dropwise, adjust
Reaction solution pH is saved as neutrality, then with chloroform extractive reaction liquid, N- methoxyl group -4- pyridones are concentrated to give after merging organic phase.
4. the preparation method of a kind of New-type spiro insecticides according to claim 2, it is characterised in that step B's is specific
Process is：Adding N- methoxyl group -4- pyridones and triphenylphosphine in reaction bulb, ammonium hydroxide is slowly added dropwise as solvent in pyridine,
5h is reacted after dripping at ambient temperature, the reaction was complete for TLC monitoring raw material, and filtering reacting liquid, with chloroform extractive reaction liquid, is closed
And N- methoxyl groups -4-aminopyridine is concentrated to give after organic phase.
5. the preparation method of a kind of New-type spiro insecticides according to claim 2, it is characterised in that step C's is specific
Process is：Nonpolar solvent is added into autoclave, opens stirring, adds formamide, N- methoxyl groups -4- is added after stirring
Aminopyridine, CO is passed through into reaction kettle, pressure in kettle is reached 0.2MPa, is warming up to 50 DEG C of reaction a period of times, and middle control is former
Material is less than 2%, and reaction terminates, and is cooled to 25~30 DEG C, and dilute hydrochloric acid is added dropwise into reaction solution, and it is 5~6 to adjust pH, there is solid analysis
Go out, filter out product, filter cake shuffles once, obtains cis-8- methoxyl groups -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone；Institute
The nonpolar solvent stated is hexamethylene, hexahydrotoluene, ethyl cyclohexane, chlorocyclohexane, preferably ethyl cyclohexane.
6. the preparation method of a kind of New-type spiro insecticides according to claim 2, it is characterised in that step D's is specific
Process is：Water is added into reaction bulb, 40 DEG C or so are heated under stirring, barium hydroxide is put into four-hole bottle, stirring and dissolving；
Add cis-8- methoxyl groups -1,3,8- thriazaspiros [4,5]-decyl- 2,4- diketone, be heated to back flow reaction 5 it is small when；Sampling prison
Survey, stop reaction after starting material left amount area percentage composition is less than 2%, after the completion of reaction, cool down 60 DEG C or so, to four-hole bottle
The concentrated sulfuric acid is inside slowly added dropwise, adjusts pH value 3 or so；10min repetition measurement pH value is stirred, stablizes and water and activity is added in backward system
Charcoal, is warming up to 80 DEG C and stirs 60 minutes；It is residue to filter out solid while hot, and filtrate heating concentrates, and concentrates body under vacuum condition
Unnecessary water in system, when steaming to thick-pasty, distillation terminates to add toluene, (be used for the toluene that is dehydrated can reuse 3 times, return every time
Used time adds one barrel of new toluene) normal pressure divides water, after moisture to the greatest extent after, be cooled to less than 30 DEG C；Centrifugal filtration, solid drying are weighed i.e.
Obtain cis-4- amino -1- methoxypyridine -4- formic acid.
7. the preparation method of a kind of New-type spiro insecticides according to claim 2, it is characterised in that step E's is specific
Process is：Methanol is added into reaction bulb, lower addition cis-4- amino -1- methoxypyridine -4- formic acid is stirred, stirs 10 points
Clock；(excessive 1.2mol) thionyl chloride is slowly added dropwise, when time for adding is about 2-3 small；Process control kettle temperature is added dropwise and is less than 60 DEG C,
It is suitable with visible micro- reflux on condenser；Be added dropwise, be warming up to back flow reaction 10 it is small when, sampling detection；Detection reaction is former
Expect that surplus area percentage composition stops reaction after being less than 1%；Solvent removed by vacuum methanol, steams to thick, stopping heating；To
Hexamethylene is added in reaction bulb, atmospheric pressure reflux separates remaining methanol in system (water knockout drum lower floor is methanol)；When having can't see
When methanol separates, stop reaction；Cooling water temperature is opened to less than 30 DEG C, filters to obtain cis-4- amino -1- methoxypyridines -4-
Methyl formate.
8. the preparation method of a kind of New-type spiro insecticides according to claim 2, it is characterised in that step F's is specific
Process is：DMF is added into reaction bulb, stirs lower addition cis-4- amino -1- methoxypyridine -4- methyl formates, then slowly
Sodium acid carbonate is added, great amount of carbon dioxide can be released, it is necessary to control addition speed in adition process, (when addition total carbonic acid hydrogen sodium
Amount 30% or so when, can accelerate add speed, do not have foam effusion) add after stir 30 minutes；Add ethyl acetate,
It is put into ice-water bath, reaction solution is cooled to 0 DEG C；Start dropwise addition 2,5- dimethyl benzene chloroacetic chlorides, control 0~5 DEG C of temperature, are added dropwise
Speed is controlled with temperature；After being added dropwise, when 0~5 DEG C of stirring reaction 5 is small, sampling monitoring reaction process, when starting material left is small
When 2%, reaction terminates；Add KF/Al2O3, open stirring；And being passed through nitrogen to bubbler has bubble to emerge.Control kettle temperature 20
~30 DEG C and nitrogen protection, when this temperature stirring reaction 2 is small, sampling detection, after raw material area percentage content is less than 0.5%
Stop reaction；Vacuum is opened to -0.1Mpa, 80~90 DEG C of kettle temperature, decompression is lower except neat solvent is waited to steam to thick-pasty, is cooled to 40
After DEG C, nitrogen protection is opened, after water (paying attention to phenomenon change and temperature change in kettle) completion of dropwise addition is added dropwise into system, stirring
15min, disposably adds remaining water after stablizing, and 20min, mistake are stirred after being slow added into the NaOH solution that concentration is 6%
Filter out KF/Al2O3(repeatable to utilize), static layering, upper strata floccule point falls to discard, and lower aqueous layer retains, and hydrochloric acid acid is added dropwise
Change, have in (acid adding speed needs to control, and the moment that too fast addition speed can separate out product wraps up impurity and forms lump) kettle
A large amount of solids separate out, and when pH value reaches 3~4, continue to stir filtering out solid product after a period of time and obtain cis-3- (2,5- bis-
Aminomethyl phenyl) -8- methoxyl groups -2- oxo -1,8- diazaspiracyclics [4,5] decyl- 3- alkene -4- alcohol.
9. the preparation method of a kind of New-type spiro insecticides according to claim 2, it is characterised in that step G's is specific
Process is：DMSO is added into reaction bulb；Dry cis-3- (2,5- 3,5-dimethylphenyls) -8- is added under stirring into bottle
Methoxyl group -2- oxo -1,8- diazaspiracyclics [4,5] decyl- 3- alkene -4- alcohol；Hydrazine hydrate is slowly added to after stirring, addition finishes tune
Whole temperature is to 150 DEG C；Reacted under air atmosphere, react and terminate when starting material left is less than 1%；Added into reaction bulb
A certain amount of water；Stirring adds a certain amount of chloroform extractive reaction liquid after twenty minutes, and extraction merges organic phase afterwards three times, and concentration has
Machine is mutually isolated through silica gel column chromatography
10. application of the New-type spiro insecticides as claimed in claim 1 in insecticidal materials are prepared.
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| CN107857722A (en) * | 2017-11-21 | 2018-03-30 | 河南紫微星化学有限公司 | A kind of novel processing step of spiral shell worm ethyl ester |
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| TW200530215A (en) * | 2003-12-12 | 2005-09-16 | Syngenta Participations Ag | Chemical compounds |
| CN103097391A (en) * | 2010-07-09 | 2013-05-08 | 雷科尔达蒂爱尔兰有限公司 | Novel spiroheterocyclic compounds as mGlu5 antagonists |
| CN103190433A (en) * | 2013-04-20 | 2013-07-10 | 海利尔药业集团股份有限公司 | Pesticide composition with spirotetramat and dinotefuran |
| CN107325099A (en) * | 2017-06-05 | 2017-11-07 | 李芷琪 | The preparation method of piperidines with insecticidal activity and the triazole derivative of 4,5 dihydro of pyrido 1,2,3 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| TW200530215A (en) * | 2003-12-12 | 2005-09-16 | Syngenta Participations Ag | Chemical compounds |
| CN103097391A (en) * | 2010-07-09 | 2013-05-08 | 雷科尔达蒂爱尔兰有限公司 | Novel spiroheterocyclic compounds as mGlu5 antagonists |
| CN103190433A (en) * | 2013-04-20 | 2013-07-10 | 海利尔药业集团股份有限公司 | Pesticide composition with spirotetramat and dinotefuran |
| CN107325099A (en) * | 2017-06-05 | 2017-11-07 | 李芷琪 | The preparation method of piperidines with insecticidal activity and the triazole derivative of 4,5 dihydro of pyrido 1,2,3 |
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| CN107857722A (en) * | 2017-11-21 | 2018-03-30 | 河南紫微星化学有限公司 | A kind of novel processing step of spiral shell worm ethyl ester |
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