CN103242323B - Nitrogen (sulfur) containing bridge ring compound with insecticidal activity, preparation method and application - Google Patents

Nitrogen (sulfur) containing bridge ring compound with insecticidal activity, preparation method and application Download PDF

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CN103242323B
CN103242323B CN201210025856.5A CN201210025856A CN103242323B CN 103242323 B CN103242323 B CN 103242323B CN 201210025856 A CN201210025856 A CN 201210025856A CN 103242323 B CN103242323 B CN 103242323B
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compound
isomer
cis
trans
alkyl
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CN103242323A (en
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李忠
徐晓勇
徐仁博
钱旭红
邵旭升
须志平
曾步兵
宋恭华
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East China University of Science and Technology
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Abstract

The invention relates to a nitrogen (sulfur) containing bridge ring compound with insecticidal activity, a preparation method and an application. Specifically, the invention discloses a compound with a general formula I or an optical isomer, a cis-trans-isomer or an agricultural pharmacology acceptable salt of the compound, and a preparation method thereof, wherein R1, R2, R3, R4, R5, R6, R, m, X and Z are respectively as defined in the specification. The invention also discloses an agricultural composition comprising the above compound and an application thereof. The above compound has high insecticidal activity for homoptera and lepidoptera agriculture and forestry insects, such as aphids, plant hoppers, whiteflies, cotton bollworms, prodenia litura, armyworm, etc. The general formula 1 is shown in the specification.

Description

Nitrogenous (sulfur) endocyclic compound with insecticidal activity, preparation and purposes
Technical field
The present invention relates to a kind of nitrogenous (sulfur) bridged ring class neonicotinoid insecticide, and its preparation method and application.
Technical background
20th century the mid-80 Beyer Co., Ltd (Bayer) develop first anabasine insecticide imidacloprid, become One of most successful novel pesticide, the anabasine insecticide with imidacloprid as representative is high because of insecticidal activity, and insecticidal spectrum is wide, right Mammal and aquatic animal toxicity are low, and have good system physical property and appropriate field stability and environment friendly, into For the important hot fields of New pesticides discovery.Develop later and in succession thiacloprid, clothianidin, Diacloden, Acetamiprid, alkene pyridine worm A series of nicotinic insecticides such as amine, MTI-446.Anabasine insecticide is high because of insecticidal activity, and insecticidal spectrum is wide, to mammal It is low with aquatic animal toxicity, and have good system physical property and appropriate field stability, have become the important of pesticides discovery Hot fields.
But the more serious resistance problem for causing frequently is used because imidacloprid is excessive and due to structural similarity Cross resistance between the neonicotinoid insecticide brought, limits to a certain extent the application of such compound, becomes restriction The major issue of such compound development, while anabasine insecticide is mainly efficient to Homoptera and coleopteran pest, its phase The medication selectivity in terms of pest control is also limit to narrower insecticidal spectrum.
Therefore, to carrying out structure of modification with highly active Nitromethylene compounds, new, more efficient chemical combination is obtained Thing, solves the resistance problem of anabasine insecticide, expands insecticidal spectrum so as to which it is that the present invention needs to solve to be applied to insecticide Technical problem.
The content of the invention
The invention provides new efficient pesticides, improve the insecticidal activity of anabasine compound, parasite killing is expanded Spectrum, solves problems of the prior art.
Present invention aim at, there is provided compound of the efficient pest control of a class and preparation method thereof.
Another object of the present invention be for growth in and results crop by attack of insect and invade and harass and guarantor is provided Shield.
The present invention introduces nitrogenous (sulfur) bridged ring on the Nitromethylene of existing nitro-methylene-type neonicotinoid insecticide, A kind of new anabasine compound is synthesized, such compound has significant insecticidal activity, and insecticidal spectrum is wide.
In a first aspect of the present invention, there is provided a kind of compound with structure shown in formula 1, or the compound Acceptable salt in optical isomer, cis-trans-isomer or Pesticide Science：
Formula 1
In formula：
R1For nitrogenous, oxygen and/or five yuan or hexa-member heterocycle base of sulfur, five yuan or hexa-atomic of the nitrogenous of halo, oxygen and/or sulfur Heterocyclic radical, or substituted or unsubstituted phenyl, wherein, the substituent group is one or more in being selected from the group：Halogen, C1-4Haloalkyl or C1-4Halogenated alkoxy；
R2And R3It is each independently H, saturation or unsaturation C1-8Alkyl, pi-allyl, benzyl, C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, carbobenzoxy, C2-6Alkynyl-carbonyl, C2-3Thiazolinyl-carbonyl, C3-6Cycloalkyl-carbonyl, benzoyl, or Person is selected from halogen atom, saturation or unsaturation C by one or more1-8Alkyl, C1-8Haloalkyl, saturation or unsaturation C1-8Alcoxyl Base or C1-8The benzoyl that the substituent group of alkyl-carbonyl is replaced, furanylcarbonyl or N, N- dimethyl-carbonyl；Or
R2And R3Collectively form-CH2-CH2- ,-CH2-CH2-CH2- or-CH2-MRc-CH2-, M is be selected from the group miscellaneous in formula Atom：N, O or S, Rc is the substituent group on hetero atom, selected from H, saturation or unsaturation C1-8Alkyl or alkoxyl, pi-allyl, benzyl Base, phenyl, C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, carbobenzoxy, C2-6Alkynyl-carbonyl, C2-3Thiazolinyl-carbonyl, C3-6Cycloalkyl-carbonyl, benzoyl, or it is selected from halogen atom, saturation or unsaturation C by one or more1-8Alkyl, C1-8Halogen Substituted alkyl, C1-8Alkoxyl or C1-8The benzoyl that the substituent group of alkyl-carbonyl is replaced, furanylcarbonyl or N, N- dimethyl carbonyl Base；
X independently is N, S, SO or SO2；
Wherein, as X=N, R4It independently is H, saturation or unsaturation C1-8Alkyl, C1-8Haloalkyl, sulfonyl, allyl Base, benzyl, saturation or unsaturation C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, carbobenzoxy, C2-6Alkynyl-carbonyl, C2-3Thiazolinyl-carbonyl, C3-6Cycloalkyl-carbonyl, benzoyl；Or it is selected from halogen atom, saturation or unsaturation by one or more C1-8Alkyl, C1-8Haloalkyl, C1-8Alkoxyl or C1-8The benzoyl that the substituent group of alkyl-carbonyl is replaced, furanylcarbonyl Or N, N- dimethyl-carbonyl；Or contain selected from phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furan, thiophene, oxazoles, quinoline, benzo One kind in nitrogen (oxygen, sulfur) heteroaromatic (miscellaneous) ring, wherein described fragrance (miscellaneous) ring is unsubstituted or is selected from the following group Substituent group is replaced：Halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, dimethylamino, saturation or unsaturation C1-4Alkyl, C1-4 Alkoxyl, C1-4Haloalkyl, or C1-4Alkyl-carbonyl；
Or as X=N, R4- YR can also independently beaRbStructure, wherein Y independently are N, S, SO or SO2；
RaAnd RbIt is each independently H, saturation or unsaturation C1-8Alkyl, pi-allyl, benzyl, C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, carbobenzoxy, C2-6Alkynyl-carbonyl, C2-3Thiazolinyl-carbonyl, C3-6Cycloalkyl-carbonyl, benzoyl；Or Person is selected from halogen atom, saturation or unsaturation C by one or more1-8Alkyl, C1-8Haloalkyl, C1-8Alkoxyl or C1-8Alkyl- The benzoyl that the substituent group of carbonyl is replaced, furanylcarbonyl or N, N- dimethyl-carbonyl；Or selected from phenyl ring, pyridine, naphthalene nucleus, Thiazole, pyrimidine, furan, thiophene ， oxazoles, the one kind in quinoline fragrance (miscellaneous) ring, or above-mentioned fragrance (miscellaneous) ring are optionally by halogen Element, itrile group, nitro, hydroxyl, carboxyl, saturation or unsaturation C1-4Alkyl, C1-4Alkoxyl, C1-4Alkyl-carbonyl, methylamino, or C1-4Haloalkyl is replaced；
Or RaAnd RbCollectively form-CH2-CH2- ,-CH2-CH2-CH2- or-CH2-MRc-CH2-, M is to be selected from the group in formula Hetero atom：N, O or S；Rc is the substituent group on hetero atom, selected from H, saturation or unsaturation C1-8Alkyl, pi-allyl, benzyl, benzene Base, C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, carbobenzoxy, C2-6Alkynyl-carbonyl, C2-3Thiazolinyl-carbonyl, C3-6Ring Alkyl-carbonyl, benzoyl, or it is selected from halogen atom, saturation or unsaturation C by one or more1-8Alkyl, C1-8Alkyl halide Base, C1-8Alkoxyl or C1-8The benzoyl that the substituent group of alkyl-carbonyl is replaced, furanylcarbonyl or N, N- dimethyl-carbonyl； Or
Work as X=S, SO, or SO2When, R4Do not exist；
M is 1～3 integer, and works as m=1,2, or when 3, compound respectively shown in formula A, B, C；
M=1 m=2 m=3
Formula A Formula B formula c
In above-mentioned various (formula 1, A, B and C), R5、R6、R7、R8、R9、R10、R11And R12H is each independently, halogen is satisfied And/or unsaturation C1-8Alkyl, pi-allyl, benzyl, saturation or unsaturation C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy carbonyl, benzene Oxygen carbonyl, C2-6Alkynylcarbonyl groups, C2-3Alkenyl carbonyl, C3-6Naphthene base carbonyl, aromaticacyl radical；Or it is selected from halogen by one or more Atom, saturation or unsaturation C1-8Alkyl, C1-8Haloalkyl, C1-8Alkoxyl or C1-8The virtue that the substituent group of alkyl-carbonyl is replaced Fragrant acyl group, furanylcarbonyl or N, N- dimethyl-carbonyl；C1-8Saturation or unsaturated alkoxyl, halo C1-8Saturation or unsaturated alcoxyl Base, C1-8Alkyl-ester base (RCOO-), C1-8Alkyl-sulfonyl ester group or fluoroform sulfonyl ester；Or for unsubstituted or substituted benzene Ring, pyridine, naphthalene nucleus, furan or quinoline, the substituent group is selected from the group：Halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, Dimethylamino, saturation or unsaturation C1-8Alkyl, C1-8Alkoxyl, C1-8Haloalkyl, C1-8Alkyl-carbonyl；
Z is nitro, cyano group, ester group, aldehyde radical, carboxyl, trifluoromethyl, trifluoroacetyl group, or trifyl.
In another preference, R1It is selected from：Unsubstituted or substituted pyridine radicals, thiazolyl, pyrimidine radicals, tetrahydrofuran base, Oxazolyl or its halides, wherein, the substituent group is one or more in being selected from the group：Halogen, C1-4Haloalkyl or C1-4Halogenated alkoxy.
In another preference, R1It is selected from：The pyridine radicals of halo, the thiazolyl of halo, the pyrimidine radicals of halo, the four of halo Hydrogen furyl or halo oxazolyls；More preferably described halides are chloro thing.
In another preference, R2、R3Collectively form-CH2-CH2- ,-CH2-CH2-CH2- or-CH2-MRc-CH2-, wherein M For the hetero atom being selected from the group：N, O or S；Rc is the saturation on hetero atom or unsaturation C1-8Alkyl or alkoxyl.
In another preference, R2And R3For hydrogen or saturation or unsaturation C1-8Alkyl, or R2And R3Collectively form-CH2- CH2- or-CH2-CH2-CH2-。
In another preference, R2And R3For hydrogen or C1-8Alkyl, preferred hydrogen, methyl or ethyl, or R2And R3Common structure Into-CH2-CH2- or-CH2-CH2-CH2-。
In another preference, X is preferably N, S, SO, or SO2。
In another preference, as X=N, R4It independently is H, saturation or unsaturation C1-8Alkyl, pi-allyl, benzyl, Saturation or unsaturation C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, carbobenzoxy, C2-6Alkynyl-carbonyl, C2-3Thiazolinyl-carbonyl Base, C3-6Cycloalkyl-carbonyl, benzoyl；Or it is selected from halogen atom, saturation or unsaturation C by one or more1-8Alkyl, C1-8 Haloalkyl, C1-8Alkoxyl or C1-8The benzoyl that the substituent group of alkyl-carbonyl is replaced, furanylcarbonyl or N, N- dimethyl Carbonyl；Or selected from phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furan, thiophene ， oxazoles, the one kind in quinoline fragrance (miscellaneous) ring, Above-mentioned fragrance (miscellaneous) ring is optionally by halogen, itrile group, carboxyl, nitro, hydroxyl, methylamino, C1-4Haloalkyl is replaced.
In another preference, as X=N, R4- YR can also independently beaRbStructure, wherein Y independently are N, S, SO Or SO2；RaAnd RbIt is each independently H, saturation or unsaturation C1-8Alkyl, pi-allyl, phenyl, benzyl, C1-8Alkoxy -C1-8Alkane Base, C1-8Alkoxy-carbonyl, or carbobenzoxy；Or RaAnd RbCollectively form-CH2-CH2- ,-CH2-CH2-CH2- or-CH2- MRc-CH2-, M is the hetero atom being selected from the group in formula：N, O or S；Rc is the substituent group on hetero atom, selected from H, saturation or insatiable hunger And C1-8Alkyl, pi-allyl, benzyl, phenyl, C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, or carbobenzoxy.
In another preference, as X=N, R4It independently is H, saturation or unsaturation C1-8Alkyl, or selected from phenyl ring, Pyridine, naphthalene nucleus, thiazole, pyrimidine, furan, thiophene ， oxazoles, the one kind in fragrance (miscellaneous) ring of quinoline；In another preference, when During X=N, R4Preferably H, methyl, ethyl, phenyl,Sulfonyl,
In another preference, work as X=S, SO, or SO2When, R4Do not exist.
In another preference, m is 1～3 integer, and as m=1,During m=2, During m=3,Wherein, it is above-mentioned it is various in, R7、R8、R9、R10、R11And R12Such as institute in first aspect present invention Definition.
In another preference, R5、R6、R7、R8、R9、R10、R11And R12It is each independently H, halogen, saturation or unsaturation C1-8Alkyl, C1-8Saturation or unsaturated alkoxyl, halo C1-8Saturation or unsaturated alkoxyl, C1-8Alkyl-ester base (RCOO-), C1-8Alkyl-sulfonyl ester group or fluoroform sulfonyl ester；Or phenyl ring, pyridine, naphthalene nucleus, furan or the quinoline to replace, it is described to take Dai Ji is selected from the group：Halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, dimethylamino, saturation or unsaturation C1-8Alkyl, C1-8 Alkoxyl, C1-8Haloalkyl, C1-8Alkyl-carbonyl.
In another preference, R5、R6、R7、R8、R9、R10、R11And R12It is each independently H, saturation or unsaturation C1-8Hydrocarbon Base, halogen, C1-8Saturation or unsaturated alkoxyl, halo C1-8Saturation or unsaturated alkoxyl, C1-8Alkyl-ester base (RCOO-), C1-8Alkyl-sulfonyl ester group or fluoroform sulfonyl ester.
In another preference, R5、R6、R7、R8、R9、R10、R11And R12It is each independently hydrogen, methyl, chlorine, bromine, methoxy Base or ethyoxyl；It is preferred that hydrogen, methyl, or methoxyl group.
In another preference, Z is nitro, cyano group, ester group, aldehyde radical, carboxyl, trifluoromethyl, trifluoroacetyl group, or trifluoro Mesyl.
In another preference, the preferred nitros of Z.
In a second aspect of the present invention, there is provided a kind of agriculturally useful compositions, it is included：
Compound, its optical isomer described in the first aspect present invention of (a) 0.0001-99.99 weight %, along anti- Acceptable salt or combinations thereof in isomer or Pesticide Science；And
Acceptable carrier and/or excipient in (b) Pesticide Science.
In a preference, component (a) accounts for 0.01-99.9 weight % of the agriculturally useful compositions, preferred 0.05-90 weights Amount %.
In another preference, the agriculturally useful compositions are used to killing or preventing the insect being selected from the group：Coleoptera, squama wing Mesh, Semiptera, Orthoptera, Isoptera or dipteral insect.
In another preference, the insect has pierce-suck type or rasping-sucking mouthparts.
In another preference, the insect is aphid, plant hopper, aleyrodid, leafhopper, thrips, bollworm, Pieris rapae, pickles Moth, Prodenia litura or mythimna separata.
In another preference, the agriculturally useful compositions also include other active substances, and described other active substances are selected from： Insecticide, bait formulation, antibacterial, acaricide, nematicide, antifungal or growth control agent.
In a third aspect of the present invention, there is provided the purposes of agriculturally useful compositions described in second aspect present invention, for killing Or the insect of prevention agricultural pests, sanitary insect pest and harm animal health；Or as killing or prevent agricultural pests, health Insect and the insecticides of harm animal health.
In a fourth aspect of the present invention, there is provided a kind of method for preparing agriculturally useful compositions described in second aspect present invention, Including step：By in the compound described in (a) first aspect present invention, its optical isomer, cis-trans-isomer or Pesticide Science Acceptable salt or combinations thereof；Mixed with acceptable carrier and/or excipient in (b) Pesticide Science, so as to shape Into agriculturally useful compositions.
In a fifth aspect of the present invention, there is provided a kind of parasite killing and/or insect-prevention method, methods described is included first aspect Described in compound or the compositionss described in second aspect put on plant, the animal that be subjected to or can suffer from insect pest In body, the soil around it or environment.
In a sixth aspect of the present invention, there is provided compound described in first aspect, its optical isomer, cis-trans-isomer Or in Pesticide Science acceptable salt or combinations thereof purposes, for prepare for kill or prevent agricultural pests, health evil Worm and the insecticides of harm animal health.
In a seventh aspect of the present invention, there is provided compound, its optical isomer described in first aspect, cis-trans-isomer Or in Pesticide Science acceptable salt preparation method, as X=N, including step：
In polar solvent, in the presence of the acid of catalytic amount, by compound W and R4NH2Inorganic acid salt or acylate, Reacted with formula A0 compound, formula B0 compound or formula C0 compound respectively, so as to obtain formula A1 compound, formula B1 respectively Compound, or formula C1 compound；
It is above-mentioned it is various in, R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12With determine in Z such as first aspect present invention Justice.
In another preference, the acid of the catalytic amount is one or more Bronsted acid or Louis in being selected from the group Acid：Hydrochloric acid, acetic acid, sodium dihydrogen phosphate, p-methyl benzenesulfonic acid, trifluoroacetic acid, boron trifluoride, aluminum chloride, ferric chloride, chlorination Magnesium, cobaltous chloride, strontium chloride, Palladous chloride. or Nickel dichloride..
In another preference, the polar solvent is acetonitrile.
In another preference, the reaction temperature is -78-50 DEG C, preferably -20-40 DEG C.
In another preference, the response time is 2-48 hours, preferably 6-24 hours.
In a eighth aspect of the present invention, there is provided compound, its optical isomer described in first aspect present invention, along anti- The preparation method of acceptable salt in isomer or Pesticide Science, as X=S, SO or SO2When, including step：
(1) ' compound, formula B ' compound or formula C in polar solvent, by formula A ' compound and CH3I reaction after, again and Na2S reacts, so as to obtain formula A2 compound, formula B2 compound or formula C2 compound respectively；
It is above-mentioned it is various in, R1、R2、R3、R5、R6、R7、R8、R9、R10、R11、R12With Z as defined in first aspect present invention；
(2) in atent solvent, by formula A2 compound, formula B2 compound or formula C2 compound and benzoyl hydroperoxide (mCPBA) react, so as to obtain formula A3 compound, formula A4 compound, formula B3 compound, formula B4 compound, formula C3 chemical combination respectively Thing, formula C4 compound；
It is above-mentioned it is various in, R1、R2、R3、R5、R6、R7、R8、R9、R10、R11、R12With Z as defined in first aspect present invention, X3=SO, X4=SO2。
In another preference, the atent solvent is dichloromethane.
It should be understood that within the scope of the present invention, above-mentioned each technical characteristic of the present invention and have in below (eg embodiment) Can be combined with each other between each technical characteristic of body description, so as to constitute new or preferred technical scheme.As space is limited, exist This no longer tires out one by one states.
Specific embodiment
The present inventor by long-term and in-depth study, in the structure base of existing nitro-methylene-type neonicotinoid insecticide Active pharmacophore Nitromethylene is remained on plinth, by dialdehyde, primary amine hydrochlorate, iodomethane, sodium sulfide, benzoyl hydroperoxide With nitromethylene-compound reaction, a kind of new miscellaneous bridged ring anabasine compound is synthesized, the parasite killing of the compound is lived Property significantly improve, and with expand insecticidal spectrum.On this basis, inventor completes the present invention.
Group definition
As used herein, term " C1-8Alkyl " refers to the alkyl with 1-8 carbon atom, thiazolinyl, alkynyl, cycloalkyl, ring Only carbon containing, the saturation of hydrogen or the unsaturated group such as thiazolinyl, aryl, preferred C1-8Alkyl, C2-8Thiazolinyl or C2-8Alkynyl.
Term " thiazolinyl " refers to the thiazolinyl of the straight or branched with 2-8 carbon atom, such as vinyl, pi-allyl, 1- third Thiazolinyl, isopropenyl, 1-butylene base, crotyl or similar group.
Term " alkynyl " refers to the alkynyl of the straight or branched with 2-8 carbon atom, such as acetenyl, propinyl etc..
Term " saturation or unsaturation C1-8Alkyl " includes C1-8Alkyl, C2-8Thiazolinyl and C2-8Alkynyl.
Term " cycloalkyl " cyclopropyl, cyclobutyl, cyclopenta, cyclohexyl or suberyl etc..
As used herein, term " C1-8Alkyl " refers to the straight or branched alkyl with 1-8 carbon atom, such as methyl, second Base, propyl group, isopropyl, butyl, isobutyl group, sec-butyl, the tert-butyl group or similar group.
Term " C1-8Alkoxyl " refers to the straight or branched alkoxyl with 1-8 carbon atom, for example methoxyl group, ethyoxyl, Propoxyl group, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy or similar group.
Term " halogen " refers to fluorine, chlorine, bromine or iodine.Term " halo " refers to above-mentioned by one or more identical or different The group that halogen atom replaces, such as trifluoromethyl, pentafluoroethyl group or similar group.
Term " five yuan or hexa-member heterocycle base " refers to containing one or more selected from heteroatomic five yuan or hexa-atomic of nitrogen, oxygen or sulfur Ring, such as pyridine radicals, thiazolyl, pyrimidine radicals, tetrahydrofuran base, Huo oxazolyls etc..
The groups such as term " sulfonyl " methylsulfonyl, ethylsulfonyl, trifluoromethyl sulfonyl.
Term " aromaticacyl radical " includes the groups such as benzoyl, picolinoyl.
The compound of the present invention can contain one or more asymmetric centers, and therefore be mixed with raceme, raceme The form of thing, single enantiomer, diastereomeric compound and single diastereomer occurs.There may be it is asymmetric in The heart, depending on the property of various substituent groups on molecule.Each this asymmetric center will independently produce two optical isomers, And all possible optical isomer and non-enantiomer mixture and pure or partial-purified compound are included in the model of the present invention Within enclosing.All isomeric forms of the present invention including compound.
The insecticidal activity of active substance of the present invention
Term " active substance of the present invention " or " reactive compound of the present invention " refer to that the compounds of this invention, its optics are different Acceptable salt in structure body, cis-trans-isomer or Pesticide Science, it has the Nitromethylene structure of pyrroles and pyrrolin condensed ring, It has significant insecticidal activity, and insecticidal spectrum is wide, and stability is strong.
Term " acceptable salt in Pesticide Science " means that the compound of formula 1 forms insecticide medicine with suitable acid or alkali Acceptable salt on.It is preferred that the salt is the anion salt of the compound of formula 1.It is preferred that the salt is water miscible.Represent Property, the acid-addition salts formed by the compound of formula 1 include the salt that mineral acid is formed, such as hydrochlorate, phosphate, sulfate, nitre Hydrochlorate etc.；And including the salt that organic acid is formed, such as acetate, benzoate etc..
The active substance of the present invention can serve as controlling and eliminating extensive agriculture and forestry plant insect, the insect of stored grains, danger Insect and public health insect of evil animal health etc..In this manual, " insecticide " is that have preventing and treating mentioned above The general designation of the material of the effect of all insects.
The example of insect is included but is not limited to：Coleopteron, such as sitophilus zea-maises (Sitophilus zeamais), red plan paddy Steal (Tribolium castaneum), potato bug (Henosepilachna vigintioctomaculata), 28 Star ladybug (Henosepilachna sparsa), agriotes fussicollis (Agriotes fuscicollis), red foot green gold Testudiniss (Anomala cupripes), beautiful tortoise with four lines (Popillia quadriguttata), colorado potato beetles (Monolepta Hieroglyphica), ponderous borer (Monochamus alternatus), rice root weevil (Echinocnemus squameus), bubble Folium paulowniae first (Basiprionota bisignata), longicorn beetle (Anoplophora chinensis), mulberry borer (Apriona Germari), umbilicuss abdomen bark beetle (Scolytus schevy), or Agriotes subrittatus Motschulsky (Agriotes fuscicollis)；Lepidoptera Insecticide, such as waves malicious pretty young woman (Lymantria dispar), tent caterpillar (Malacosoma neustria testacea), Buxus sinica (Rehd.et Wils.) thin,tough silk Wild snout moth's larva (Diaphania perspectalis), Clania variegata Snellen (Clania variegata), cnidocampa flavescens walker (Cnidocampa Flavscens), dendrolimus punctatus (Dendrolimus punctatus), orgyia antiqua (Orgyia gonostigma), Cortex Populi dividianae is saturating Wing moth (Paranthrene tabaniformis), Prodenia litura (Spodoptera litura), striped rice borer (Chilo Suppressalis), Pyrausta nubilalis (Hubern). (Ostrinia nubilalis), meal moth (Ephestia cautella), lap moth (Adoxophyes orana), Li Shie (laspeyresia splendana), black cutworm (Agrotis fucosa), greatly Galleria mellonella waxmoth (Galleria mellonella), diamond-back moth (Plutella xylostella), Fructus Citri tangerinae lyonetid (Phyllocnistis ), or oriental armyworm (Mythimna separata) citrella；Homoptera insect, such as rice green leafhopper (Nephotettix Cincticeps), brown plant-hopper (Nilaparvata lugens), Kang Shi mealybugs (Pseudococcus comstocki), arrow Sharp a red-spotted lizard (Unaspis yanonensis), black peach aphid (Myzus persicae), cotten aphid (Aphis gossypii), radish aphid (Lipaphis erysimi pseudobrassicae), pears class lace bug (Stephanitis nashi), or aleyrodid (Bemisia tabaci)；Orthopteran, such as Groton bug (Blattella germanica), the big Lian (Periplaneta in the U.S. Americana), African mole cricket (Gryllotalpa africana), or Asiatic migratory locust (Locus migratoria)；Isoptera Insecticide, such as S.invicta Buren (Solenopsis invicta), or Coptotermes formosanus Shtrari． (Coptotermes formosanus)；Diptera Insecticide, such as housefly (Musca domestica), Aedes aegypti (Aedes aegypti), Hylemyia Platura Meigen (Delia platura), culex (Culex sp.), or Anopheles sinensises (Anopheles sinensis)；
The insect of harm animal health, such as boophilus micropluses (Boophilus microplus), haemaphysalis longicornises (Haemaphysalis longicornis), hyalomma anatolicum anatolicum (Hyalomma anatolicum), bomb fly (Hypoderma Spp.), distoma hepaticum (Fasciola hepatica), bayesian moniezia (Moniezia benedeni), oersted line Worm (Ostertagia spp.), Trypanosoma evansi (Trypanosoma evansi, Babesia bigemina), coccidiosiss (Coccidium) etc..
Compound according to the present invention especially to pierce-suck type, rasping-sucking mouthparts insect such as：Aphid, leafhopper, plant hopper, thrips, The agriculture and forestry injurious insects such as aleyrodid have specially good effect.
Insecticides containing active substance of the present invention
The active substance of the present invention can be in a conventional way prepared into insecticides.These reactive compounds can do Into conventional preparation, such as solution, Emulsion, suspensoid, powder, foam, paste, granule；Aerosol, uses active substance Dipping natural and synthesis material, the microcapsule in polymer, for the coating compound recipe of seed, and with burner one The preparation that block is used, such as sootiness cartridge case, sootiness tank and sootiness disk, and ULV harls (Cold mist) and hot mist (Warm Mist) preparation.
The available known method production of these preparations, for example, reactive compound is mixed with agent is expanded, and these expand agent just Liquid or liquefied gas or solid diluent or carrier, and can arbitrarily from surfactant be emulsifying agent and/or point Powder and/or formation of foam agent.For example when expansion agent is made with water, organic solvent also is used as auxiliary agent.
When making diluent or carrier with liquid flux, substantially suitably, such as：Arene, such as dimethylbenzene, toluene Or alkylnaphthalene；The fragrance or the fat hydrocarbon of chlorination, such as chlorobenzene, vinyl chloride or dichloromethane of chlorination；Fat hydrocarbon, such as ring Hexane or paraffin, such as mineral oil fractions；Alcohols, such as ethanol or ethylene glycol and their ether and lipid；Ketone, such as third Ketone, butanone, methyl iso-butyl ketone (MIBK) or Ketohexamethylene；Or the polar solvent being of little use, such as dimethylformamide and dimethyl are sub- Sulfone, Yi Jishui.
The diluent or carrier of liquefied gas is said, refer to that the liquid of gas will be become at normal temperatures and pressures, such as gas is molten The hydro carbons and butane of glue propellant, such as halogenation, propane, nitrogen and carbon dioxide.
Solid carrier can use the natural mineral for grinding, such as Kaolin, clay, Talcum, quartz, active hargil to cover De- soil, or kieselguhr, and the mineral of grinding synthesis, the silicic acid of such as high degree of dispersion, aluminium oxide and silicate.For granule Solid carrier is natural announcement stone pulverize and classification, such as calcite, marble, Pumex, meerschaum and dolomite, Yi Jiwu Machine and the granule of organic coarse powder synthesis, and the granule of organic material such as wood sawdust, Exocarpium cocois (Cocos nucifera L), maize cob and tobacco stems etc..
The emulsifying row of non-ionic and anion can be used as emulsifying agent and/or formation of foam agent.Such as polyoxyethylene-fatty Esters of gallic acid, polyoxyethylene-fatty alcohol ethers, such as alkaryl Polyethylene Glycol ethers, alkyl sulfonates, alkylsurfuric acid esters, Aryl sulfonic acid esters and albumin hydrolyzate.Dispersant includes, such as lignin sulfite waste liquor and methylcellulose.
Can use binding agent in the formulation, for example carboxymethyl cellulose and with the natural of powder, granule or emulsion form and The polymer of synthesis, such as arabic gum, polyvinyl alcohol and polyvinyl acetate.
Can be with coloring agent such as inorganic dyestuff, such as ferrum oxide, oxidation brill and Prussian blue；Organic dyestuff, if any engine dyeing Material, such as azo dyes or metal phthalcyanine；With use trace nutritional agent, such as ferrum, suddenly, boron, copper, cobalt, the salt of aluminum and zinc etc..
These reactive compounds of the present invention can make a kind of mixture and be present in their business with other reactive compounds In the use dosage form prepared in product preparation or from these preparations, these other reactive compounds are insecticide, close bait, sterilization Agent, acaricide, nematicide, antifungal, growth control agent etc..Insecticide includes, such as phosphoric acid ester, carbamate Class, cinerins, chlorinated hydrocarbons, benzoyl area kind, neires toxin and the material produced by microorganism, such as Avermectin Element.
Additionally, these reactive compounds of the present invention also can make a kind of mixture with synergist is present in their commodity In preparation in the use dosage form prepared from these preparations.Synergist is the compound for improving reactive compound effect, due to work Property compound itself is active, can also add synergist.
These preparations are usually contained and account for insecticides 0.001-99.99 weight %, preferred 0.01-99.9 weights Amount %, the more preferably reactive compound of the invention of 0.05-90 weight %.Make using the activation in dosage form from commercial preparation The concentration of compound can change in wide scope.Can be from 0.0000001- using the concentration of the reactive compound in dosage form 100% (g/v), preferably between 0.0001 and 1% (g/v).
The preparation method of the compounds of this invention
Compound shown in formula of the present invention 1 can be obtained by following method, but the condition of the method, for example react Thing, solvent, alkali, the amount of compound used therefor, reaction temperature, reaction required time etc. are not limited to explanation below.Chemical combination of the present invention Various synthetic methods describing in this manual or known in the art optionally can also be combined and easily be made by thing , such combination can readily be carried out by those skilled in the art in the invention.
Acid used in reaction is Bronsted acid or lewis acid, including (but being not limited to)：Hydrochloric acid, acetic acid, biphosphate Sodium, p-methyl benzenesulfonic acid, trifluoroacetic acid, boron trifluoride, aluminum chloride, ferric chloride, magnesium chloride, cobaltous chloride, strontium chloride, chlorination Palladium or Nickel dichloride., or its combination.
In a preference, compound shown in the structure of formula of the present invention 1 can be synthesized by following method：
(1) as X=N, methods described comprises the steps：
In polar solvent (such as acetonitrile), in the presence of the acid of catalytic amount, under -78-50 DEG C (preferably -20-40 DEG C), will Compound W and R4NH2Hydrochlorate (such as R4NH2HCl), respectively with formula A0 compound, formula B0 compound or formula C0 compound Reaction a period of time (such as 2-48 hours, preferably 6-24 hours) is carried out, so as to obtain formula A1 compound, formula B1 chemical combination respectively Thing, or formula C1 compound；
It is above-mentioned it is various in, R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12With Z as hereinbefore defined.
The formula W compound can be the compound as shown in formula W1 or formula W2；
Wherein, in formula W1, R1It is as defined above defined in text with Z, n is the integer of 1-3；
In formula W2, R1It is as defined above defined in text with Z, R2And R3It is each independently H, saturation or unsaturation C1-8Hydrocarbon Base, pi-allyl, benzyl, C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, carbobenzoxy, C2-6Alkynyl-carbonyl, C2-3Alkene Base-carbonyl, C3-6Cycloalkyl-carbonyl, benzoyl, or it is selected from halogen atom, saturation or unsaturation C by one or more1-8Hydrocarbon Base, C1-8Haloalkyl, saturation or unsaturation C1-8Alkoxyl or C1-8The benzoyl that the substituent group of alkyl-carbonyl is replaced, furan Mutter carbonyl or N, N- dimethyl-carbonyl.
The preparation method of the compound shown in compound or formula W2 shown in formula W1 can be in prior art Conventional preparation method.
A kind of preparation method of preferably described formula W1 compound, including step：
Appropriate acetonitrile is added in (i) diamidogen, the acetonitrile lysate of Deca formula F compound under ice bath, TLC tracking react into Journey, after reaction terminates, adds substantial amounts of water, chloroform extraction to be dried in reaction mixture, and sucking filtration boils off solvent, obtains Oily liquids formula E compound；
(ii) formula E compound and formula G compound, with atent solvent (such as ethanol) solvent is made, and backflow a period of time is (such as 2-16 Hour or 4-8 hours), cooling and standings, the solid that sucking filtration is separated out obtains product formula W1 compound；
It is above-mentioned it is various in, R1With Z as hereinbefore defined, n is the integer of 1-3.
A kind of preparation method of preferably described formula W2 compound, including step：
(a)R2NH2Appropriate acetonitrile is added in aqueous solution, the acetonitrile solution of Deca formula F compound under ice bath, TLC tracking is anti- After answering process, reaction to terminate, substantial amounts of water, dichloromethane extraction is added to be dried in reaction mixture, sucking filtration boils off solvent, Obtain oily liquids formula H compound；
B () formula H compound and formula G compound, in atent solvent (such as ethanol), backflow a period of time is (such as 2-16 or 4-8 Hour), concentration, column chromatography for separation obtains product formula J compound；
C () formula J compound reacts with amine, in atent solvent (such as ethanol), reaction a period of time is (such as 4-8 under ice bath Hour), concentration, column chromatography for separation obtains formula W2 compound；
It is above-mentioned it is various in, R1It is as defined above defined in text with Z, R2And R3It is each independently H, saturation or unsaturation C1-8Alkyl, pi-allyl, benzyl, C1-8Alkoxy -C1-8Alkyl, C1-8Alkoxy-carbonyl, carbobenzoxy, C2-6Alkynyl-carbonyl, C2-3Thiazolinyl-carbonyl, C3-6Cycloalkyl-carbonyl, benzoyl, or it is selected from halogen atom, saturation or unsaturation by one or more C1-8Alkyl, C1-8Haloalkyl, saturation or unsaturation C1-8Alkoxyl or C1-8The benzoyl that the substituent group of alkyl-carbonyl is replaced Base, furanylcarbonyl or N, N- dimethyl-carbonyl.
(2) as X=S, SO or SO2When, including step：
(I) ' compound, formula B ' compound or formula C in polar solvent (such as ethanol), respectively by formula A ' compound and CH3I After reaction (2-8 hours are such as stirred at room temperature), a little ether is added, filtered, collect precipitation；By the precipitation collected and sodium sulfide reaction (as being dissolved in water together, at 80-100 DEG C, reacting 1-4 hours), after reaction terminates, concentration, column chromatography, so as to obtain formula respectively A2 compounds, formula B2 compound or formula C2 compound；
In formula, R1、R2、R3、R5、R6、R7、R8、R9、R10、R11、R12With Z as hereinbefore defined；(II) in atent solvent (such as Dichloromethane) in, respectively by formula A2 compound, formula B2 compound, or formula C2 compound and benzoyl hydroperoxide (mCPBA) reaction, Reaction 1-4 hours, after reaction completely, concentration, column chromatography, so as to obtain formula A3 compound, formula A4 compound, formula B3 chemical combination respectively Thing, formula B4 compound, formula C3 compound or formula C4 compound.
In formula, R1、R2、R3、R5、R6、R7、R8、R9、R10、R11、R12With Z as hereinbefore defined.
Wherein, formula A3 compound, formula A4 compound, formula B3 chemical combination can be respectively obtained by controlling the amount of benzoyl hydroperoxide Thing, formula B4 compound, formula C3 compound or formula C4 compound.
Main advantages of the present invention include：
A () the invention provides the novel compound of a class formation, the insecticidal activity of the compound is significantly improved；
B compound that () present invention is provided has the insecticidal spectrum for expanding, and to bean sprout and mythimna separata highly significant is all shown Insecticidal activity.
With reference to being embodied as, the present invention is expanded on further.It should be understood that these embodiments be merely to illustrate the present invention and It is not used in restriction the scope of the present invention.The experimental technique of unreceipted actual conditions in the following example, generally according to normal condition, Or according to the condition proposed by manufacturer.Unless otherwise indicated, otherwise percentage ratio and number are calculated by weight.
Embodiment 1-44：The preparation of miscellaneous bridged ring anabasine compound
The 1- of embodiment 1 ((6- chloropyridine -3- bases) methyl) -8- nitro -1,2,3,5,6,7- hexahydro -5,7- epimino miaows The synthesis of azoles simultaneously [1,2-a] pyridine (compound A-1)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the ammonium chloride of 0.531g (10.0mmol), slowly the malonaldehyde of Deca 0.360g (5.0mmol).Reaction 24 After hour, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 42%.1H NMR (400MHz, DMSO- d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=8.0Hz, 1H), 4.84 (s, 2H), 4.00 (t, J=7.6Hz, 1H), 3.90 (t, J=9.5Hz, 1H), 3.04 (m, 4H), 2.41 (m, 1H), 1.84 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 150.02,149.48,148.61,138.84,130.35,123.76, 54.68,50.86,50.62,37.44ppm；HRMS(ES+)C13H14 35ClN5O2(M+H)+, value of calculation：308.0836；Measured value： 308.0756；C13H14 37ClN5O2(M+H)+, value of calculation：310.0807；Measured value：310.0743.
The 1- of embodiment 2 ((6- chloropyridine -3- bases) methyl) -9- methyl -8- nitro -1,2,3,5,6,7- hexahydro -5,7- rings The synthesis of imine imidazole simultaneously [1,2-a] pyridine (compound A-2)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the malonaldehyde of Deca 0.360g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 34%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=1.6Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=8.0Hz, 1H), 4.84 (s, 2H), 3.36 (t, J=8.0Hz, 1H), 3.27-2.81 (m, 5H), 2.43 (m, 1H), 2.26 (s, 3H), 1.79 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 153.38,149.48,148.61,138.84,130.35,123.76, 54.68,50.62,49.95,41.67,31.15ppm；HRMS(ES+)C14H16 35ClN5O2(M+H)+, value of calculation：322.0993； Measured value：322.0778；C14H16 37ClN5O2(M+H)+, value of calculation：324.0963；Measured value：324.0765.
The 1- of embodiment 3 ((6- chloropyridine -3- bases) methyl) -9- phenyl -8- nitro -1,2,3,5,6,7- hexahydro -5,7- rings The synthesis of imine imidazole simultaneously [1,2-a] pyridine (compound A-18)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the aniline hydrochloride of 1.290g (10.0mmol), slowly the malonaldehyde of Deca 0.360g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains yellow powder sterling, and yield is 37%.1H NMR (400MHz, DMSO- d6) δ 8.71 (d, J=1.4Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=7.5Hz, 1H), 7.21 (t, J=7.5Hz, 2H), 6.94 (dd, J=7.5,1.4Hz, 2H), 6.83-6.75 (m, 1H), 4.84 (s, 2H), 4.53 (m, 2H), 3.19 (t, J=6.9Hz, 1H), 3.06 (m, 2H), 2.92 (t, J=6.9Hz, 1H), 2.75-2.65 (m, 1H), (2.27-2.17 m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 151.54,149.48,148.61,146.37, 138.84,130.35,128.57,123.76,122.46,116.84,54.68,50.62,49.95,31.66ppm；HRMS(ES +)C19H18 35ClN5O2(M+H)+, value of calculation：384.1149；Measured value：384.0974；C19H18 37ClN5O2(M+H)+, value of calculation： 386.1120；Measured value：386.0951.
The 1- of embodiment 4 ((6- chloropyridine -3- bases) methyl) -9- methyl -8- cyano group -1,2,3,5,6,7- hexahydro -5,7- rings The synthesis of imine imidazole simultaneously [1,2-a] pyridine (compound A-38)：
By 2- (1- ((6- chloropyridine -3- bases) methyl) imidazoline -2- subunits) acetonitriles of 1.170g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the malonaldehyde of Deca 0.360g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 34%.1H NMR δ 8.71 (d, J= 2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 3.85 (t, J=9.8Hz, 1H), 3.39 (t, J=8.0Hz, 1H), 3.25-2.93 (m, 3H), 2.85 (dd, J=20.1,6.9Hz, 1H), (m, the 1H) ppm of 2.49 (m, 1H), 2.26 (s, 3H), 1.79；13CNMR (100MHz, DMSO-d6)：δ 160.04,149.48, 148.61,138.84,130.35,123.76,110.63,61.65,54.68,50.62,49.95,41.67,25.77ppm； HRMS(ES+)C15H16 35ClN5(M+H)+, value of calculation：302.1094；Measured value：302.0047；C15H16 37ClN5(M+H)+, meter Calculation value：304.1065；Measured value：304.0018.
The N- of embodiment 5 ((2- diuril azoles -5- bases) methyl)-N- ethyl -2,6- dimethyl -4- nitro -2,6- diazas two The synthesis of ring [3.1.1] hept- 3- alkene -3- amine (compound A-50)：
By N- ((2- diuril azoles -5- bases) the methyl)-N- ethyl-N-methyl -2- nitroethylenes of 1.380g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.671g (10.0mmol), slowly Deca 0.360g (5.0mmol) Malonaldehyde.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 36%.1H NMR (400MHz, DMSO-d6) δ 6.76 (s, 1H), 3.24 (q, J=12.6Hz, 2H), 3.00 (s, 3H), 2.79 (s, 2H), 2.26 (s, 3H), 1.17 (t, J=12.6Hz, 3H), 0.95-1.05 (m, 2H), 0.09-0.33 (m, 2H) ppm；13C NMR (100MHz, DMSO-d6)：δ 159.18,155.82,142.12,140.55,48.03,45.58,41.67,39.81,31.94,13.15ppm； HRMS(ES+)C13H18 35ClN5O2S(M+H)+, value of calculation：344.0870；Measured value：344.0687；C13H18 37ClN5O2S(M+H )+, value of calculation：346.0840；Measured value：346.0657.
The 1- of embodiment 6 ((6- chloropyridine -3- bases) methyl) -8- nitro-N-phenyl -1,2,3,5,6,7- hexahydro -5,7- rings The synthesis of imine imidazole simultaneously [1,2-a] pyridine -9- amine (compound A-23)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the phenylhydrazine hydrochloride of 1.440g (10.0mmol), slowly the malonaldehyde of Deca 0.360g (5.0mmol).Reaction After 24 hours, pale yellow powder shape sterling is filtrated to get, yield is 47%.1H NMR (400MHz, DMSO-d6) δ 8.70 (d, J= 2.9Hz, 1H), 8.04 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.38-7.17 (m, 3H), 7.13-7.00 (m, 2H), 6.87-6.73 (m, 1H), 4.84 (s, 2H), 4.22 (t, J=9.2Hz, 1H), 3.22 (m, 2H), 3.09-2.87 (m, 3H), 2.54 (dd, J=24.8,9.2Hz, 1H), 1.98 (dd, J=24.8,9.2Hz, 1H) ppm；13C NMR (100MHz, DMSO- d6)：δ 153.91,149.48,148.61,147.96,138.84,130.35,128.97,123.76,122.18,114.39, 54.68,50.62,49.95,27.62ppm；HRMS(ES+)C19H19 35ClN6O2(M+H)+, value of calculation：399.1258；Measured value： 399.0987；C19H19 37ClN6O2(M+H)+, value of calculation：401.1229；Measured value：401.0973.
The 1- of embodiment 7 ((6- chloropyridine -3- bases) methyl)-N- isopropyl -8- nitro-N-phenyl -1,2,3,5,6,7- six Hydrogen -5, the synthesis of 7- epimino imidazo [1,2-a] pyridines -9- amine (compound A-28)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the 1- isopropyl -1- hydrazinobenzene hydrochloride salts of 1.881g (10.0mmol), slowly Deca 0.360g (5.0mmol) Malonaldehyde.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.38- 7.17 (m, 3H), 7.17-7.07 (m, 2H), 6.91 (m, 1H), 4.84 (s, 2H), 4.22 (t, J=9.0Hz, 1H), 3.26- 2.94 (m, 4H), 2.86 (dd, J=20.0,7.2Hz, 1H), 2.55 (dd, J=24.7,8.9Hz, 1H), 2.06 (dd, J= 24.8,9.0Hz, 1H), 1.22 (d, J=12.1Hz, 6H) ppm；13C NMR (100MHz, DMSO-d6)：δ 152.91,149.48, 148.61,146.29,138.84,130.35,129.34,123.76,119.82,117.79,55.61,54.68,50.62, 49.95,28.31,21.22ppm；HRMS(ES+)C22H25 35ClN6O2(M+H)+, value of calculation：441.1728；Measured value： 441.1587；C22H25 37ClN6O2(M+H)+, value of calculation：443.1698；Measured value：443.1568.
The 1- of embodiment 8 ((6- chloropyridine -3- bases) methyl) -8- nitro -1,2,3,5,6,7- hexahydro -5,7- epithio imidazoles And the synthesis of [1,2-a] pyridine (compound A-33)：
By 1- ((6- chloropyridine -3- bases) methyl) -9- methyl -8- nitro -1 of 1.605g (5.0mmol), 2,3,5,6,7- Hexahydro -5, add 20ml acetonitriles, slowly the iodine first of Deca 0.852g (6.0mmol) in 7- epimino imidazo [1,2-a] pyridines Alkane.After reaction 2 hours, brown solid is filtrated to get, yield is 91%.By brown solid 2.084g (4.5mmol) and The Na of 0.421g (5.4mmol)2S is soluble in water, under nitrogen protection, after reacting 2 hours at 85 DEG C, removes solvent, column chromatography Isolated pale yellow powder shape sterling yield is 40%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 3.74 (m, 2H), (m, the 1H) ppm of 3.26-2.97 (m, 3H), 2.93-2.80 (m, 1H), 2.53 (m, 1H), 2.06；13C NMR (100MHz, DMSO- d6)：δ 152.47,149.48,148.61,138.84,130.35,123.76,54.68,50.62,50.46,39.12ppm； HRMS(ES+)C13H13 35ClN4O2S(M+H)+, value of calculation：325.0448；Measured value：325.0285；C13H13 37ClN4O2S(M+H )+, value of calculation：327.0418；Measured value：327.0264.
N- ethyl -2 of embodiment 9,6- dimethyl -4- nitro-N- ((tetrahydrofuran -3- bases) methyl) the miscellaneous phenodiazines two of -2,6- The synthesis of ring [3.1.1] hept- 3- alkene -3- amine (compound A-64)：
By N- ethyl-N-methyl -2- nitro-N- ((tetrahydrofuran -3- bases) methyl) ethylene of 1.145g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.671g (10.0mmol), slowly Deca 0.360g (5.0mmol) Malonaldehyde.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 3.87-3.54 (m, 3H), 3.54-3.30 (m, 3H), 3.22-2.95 (m, 7H), 2.43-2.07 (m, 5H), (t, J=12.6Hz, the 3H) ppm of 2.05-1.74 (m, 2H), 1.61 (m, 1H), 1.17；13C NMR (100MHz, DMSO- d6)：δ 156.49,71.54,68.13,52.44,49.10,41.67,39.85,39.81,31.94,30.04,13.15ppm； HRMS(ES+)C14H24N4O3(M+H)+, value of calculation：297.1848；Measured value：297.1686.
The 1- of embodiment 10 ((6- chloropyridine -3- bases) methyl) -8- nitro -1,2,3,5,6,7- hexahydro -5,7- epithio imidazoles And [1,2-a] pyridine -9, the synthesis of 9- double oxides (compound A-35)：
By 1- ((6- chloropyridine -3- bases) methyl) -8- nitro -1 of 1.605g (5.0mmol), 2,3,5,6,7- hexahydro -5, 20ml dichloromethane is added in 7- epithio imidazo [1,2-a] pyridines, slowly the m-chloro peroxide of Deca 1.726g (10.0mmol) Benzoic acid.After reaction 2 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling yield for 60%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J =14.9Hz, 1H), 5.20-5.08 (m, 2H), 4.84 (s, 2H), 3.71 (m, 1H), 3.23 (m, 1H), 3.15-3.00 (m, 2H), 2.99-2.85 (m, 1H), 2.60 (m, 1H) .ppm；13C NMR (100MHz, DMSO-d6)：δ 162.29,149.48, 148.61,138.84,130.35,123.76,54.68,50.62,50.46,32.02ppm；HRMS(ES+)C13H13 35ClN4O4S (M+H)+, value of calculation：356.0346；Measured value：356.0296；C13H13 37ClN4O4S(M+H)+, value of calculation：358.0317；It is real Measured value：358.0272.
The 1- of embodiment 11 ((6- chloropyridine -3- bases) methyl) -9- nitro -2,3,5,6,7,8- hexahydro -1H-5,8- rings are sub- The synthesis of amine imidazo [1,2-a] azepine (compound B-1)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the ammonium chloride of 0.531g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction 24 After hour, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 38%.1H NMR (400MHz, DMSO- d6) δ 8.66 (d, J=2.9Hz, 1H), 8.01 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.30 (d, J=14.9Hz, 1H), 4.81 (s, 2H), 4.28 (t, J=7.3Hz, 1H), 3.96 (t, J=8.7Hz, 1H), 3.18 (t, J=13.9Hz, 1H), 3.05 (t, J=13.8Hz, 1H), 2.89 (t, J=13.7Hz, 1H), 2.69 (t, J=13.9Hz, 1H), 2.27 (s, 1H), 1.95- 1.75 (m, 1H), 1.72-1.41 (m, 2H), 1.32-1.11 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48, 148.61,138.84,130.35,123.76,64.35,54.68,50.62,49.31,29.97,27.81ppm；HRMS(ES+) C14H16 35ClN5O2(M+H)+, value of calculation：322.0993；Measured value：322.0763；C14H16 37ClN5O2(M+H)+, value of calculation： 323.0963；Measured value：323.0748.
The 1- of embodiment 12 ((6- chloropyridine -3- bases) methyl) -10- methyl -9- nitro -2,3,5,6,7,8- hexahydro -1H- The synthesis of 5,8- epimino imidazo [1,2-a] azepines (compound B-2)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 3.77-3.68 (m, 1H), 3.55-3.46 (m, 1H), 3.19 (t, J=13.8Hz, 1H), 3.06 (t, J =13.9Hz, 1H), 2.83 (t, J=13.8Hz, 1H), 2.71 (t, J=13.8Hz, 1H), 2.26 (s, 3H), 1.86-1.47 (m, 2H), 1.47-1.21 (m, 2H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,138.84, 130.35,123.76,55.70,54.68,50.62,48.79,38.45,27.89,24.75ppm；HRMS(ES+) C15H18 35ClN5O2(M+H)+, value of calculation：336.1149；Measured value：336.0986；C15H18 37ClN5O2(M+H)+, value of calculation： 338.1120；Measured value：338.0957.
The 1- of embodiment 13 ((6- chloropyridine -3- bases) methyl) -9- nitro -10- phenyl -2,3,5,6,7,8- hexahydro -1H- The synthesis of 5,8- epimino imidazo [1,2-a] azepines (compound B-18)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the aniline hydrochloride of 1.290g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains yellow powder sterling, and yield is 33%.1H NMR (400MHz, DMSO- d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 7.30-7.13 (m, 2H), 7.01-6.86 (m, 2H), 6.86-6.72 (m, 1H), 4.90-4.80 (m, 3H), 4.51 (t, J= 8.1Hz, 1H), 3.13 (m, 2H), 2.85 (m, 2H), 2.05-1.56 (m, 3H), 1.54-1.34 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,147.76,138.84,130.35,128.58,123.76,120.82, 120.25,54.68,53.23,50.62,48.79,28.68,25.78ppm；HRMS(ES+)C20H20 35ClN5O2(M+H)+, calculate Value：398.1306；Measured value：398.1278；C20H20 37ClN5O2(M+H)+, value of calculation：400.1276；Measured value： 400.1254。
The 1- of embodiment 14 ((6- chloropyridine -3- bases) methyl) -10- methyl -9- cyano group -2,3,5,6,7,8- hexahydro -1H- The synthesis of 5,8- epimino imidazo [1,2-a] azepines (compound B-49)：
By 2- (1- ((6- chloropyridine -3- bases) methyl) imidazoline -2- subunits) acetonitriles of 1.170g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=1.4Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=7.5Hz, 1H), 4.84 (s, 2H), 4.05-3.98 (m, 1H), 3.70 (t, J=3.5Hz, 1H), 3.21 (t, J=6.7Hz, 1H), 3.08 (t, J=6.8Hz, 1H), 2.95 (t, J=6.7Hz, 1H), 2.60 (t, J=6.8Hz, 1H), 2.26 (s, 3H), 1.72 (m, 2H), 1.60-1.42 (m, 1H), 1.37-1.21 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61, 138.84,130.35,123.76,119.16,58.00,57.19,54.68,50.62,48.79,38.45,27.89, 25.53ppm；HRMS(ES+)C16H18 35ClN5(M+H)+, value of calculation：316.1251；Measured value：316.1087；C16H18 37ClN5 (M+H)+, value of calculation：318.1221；Measured value：318.1057.
The N- of embodiment 15 ((2- diuril azoles -5- bases) methyl)-N- ethyl -2,8- dimethyl -4- nitro -2,8- diazas The synthesis of bicyclo- [3.2.1] octyl- 3- alkene -3- amine (compound B-62)：
By N- ((2- diuril azoles -5- bases) the methyl)-N- ethyl-N-methyl -2- nitroethylenes of 1.380g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.671g (10.0mmol), slowly Deca 0.430g (5.0mmol) Butanedial.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 6.76 (s, 1H), 4.62 (s, 1H), 4.33 (s, 1H), 3.56-3.39 (m, 2H), 3.24 (q, J= 12.6Hz, 2H), 3.00 (s, 3H), 2.26 (s, 3H), 1.79-1.25 (m, 4H), 1.17 (t, J=12.6Hz, 3H) ppm；13C NMR (100MHz, DMSO-d6)：δ 159.18,142.12,140.55,55.70,48.03,45.58,38.45,38.16, 27.18,24.75,13.15ppm；HRMS(ES+)C14H20 35ClN5O2S(M+H)+, value of calculation：358.1026；Measured value： 358.0846；C14H20 37ClN5O2S(M+H)+, value of calculation：360.0997；Measured value：360.0817.
The 1- of embodiment 16 ((6- chloropyridine -3- bases) methyl) -9- nitro-N-phenyl -2,3,5,6,7,8- hexahydro -1H-5, The synthesis of 8- epimino imidazo [1,2-a] azepines -10- amine (compound B-23)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the phenylhydrazine hydrochloride of 1.440g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction After 24 hours, pale yellow powder shape sterling is filtrated to get, yield is 47%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J= 2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.38-7.17 (m, 3H), 7.13-6.97 (m, 2H), 6.88-6.74 (m, 1H), 4.84 (s, 2H), 3.21 (m, 2H), 3.09-2.96 (m, 2H), 2.76 (t, J=14.0Hz, 1H), 1.84 (m, 2H), 1.68-1.36 (m, 2H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,147.96, 138.84,130.35,128.97,123.76,122.18,114.39,56.30,54.68,50.62,48.79,29.23, 24.86ppm；HRMS(ES+)C20H21 35ClN6O2(M+H)+, value of calculation：413.1415；Measured value：413.1296； C20H21 37ClN6O2(M+H)+, value of calculation：415.1385；Measured value：415.1273.
The 1- of embodiment 17 ((6- chloropyridine -3- bases) methyl)-N- isopropyl -9- nitro-N-phenyl -2,3,5,6,7,8- The synthesis of hexahydro -1H-5,8- epimino imidazo [1,2-a] azepine -10- amine (compound B-28)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the 1- isopropyl -1- hydrazinobenzene hydrochloride salts of 1.861g (10.0mmol), slowly Deca 0.430g (5.0mmol) Butanedial.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.38- 7.17 (m, 3H), 7.17-7.03 (m, 2H), 6.97-6.83 (m, 1H), 4.84 (s, 2H), 3.24-2.83 (m, 4H), 2.77 (t, J=14.0Hz, 1H), 1.99-1.64 (m, 3H), 1.52-1.33 (m, 1H), 1.22 (d, J=12.2Hz, 6H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,146.29,138.84,130.35,129.34,123.76,119.82, 117.79,56.43,55.61,54.68,50.62,48.79,29.91,25.30,21.22ppm；HRMS(ES+) C23H27 35ClN6O2(M+H)+, value of calculation：455.1884；Measured value：455.0425；C23H27 37ClN6O2(M+H)+, value of calculation： 457.1855；Measured value：457.0402.
The 1- of embodiment 18 ((6- chloropyridine -3- bases) methyl) -9- nitro -2,3,5,6,7,8- hexahydro -1H-5,8- epithios The synthesis of imidazo [1,2-a] azepine (compound B-33)：
By 1- ((6- chloropyridine -3- bases) methyl) -10- methyl -9- nitro -2 of 1.676g (5.0mmol), 3,5,6,7, 20ml acetonitriles are added in 8- hexahydro -1H-5,8- epimino imidazo [1,2-a] azepine, slowly Deca 0.852g (6.0mmol) iodomethane.After reaction 2 hours, brown solid is filtrated to get, yield is 89%.By brown solid 2.147g (4.5mmol) with the Na of 0.421g (5.4mmol)2S is soluble in water, under nitrogen protection, after reacting 2 hours at 85 DEG C, removes Solvent, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 38%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J =2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 3.79-3.70 (m, 1H), 3.42-3.33 (m, 1H), 3.14 (m, 2H), 2.85 (m, 2H), 2.25-2.02 (m, 2H), 1.98- (1.69 m, 2H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,138.84,130.35,123.76, 54.68,50.62,49.91,48.29,30.59,27.79ppm；HRMS(ES+)C14H15 35ClN4O2S(M+H)+, value of calculation： 339.0604；Measured value：339.0014；C14H15 37ClN4O2S(M+H)+, value of calculation：341.0575；Measured value：340.9989.
Embodiment 19N- ethyl -2,8- dimethyl -4- nitro-N- ((tetrahydrofuran -3- bases) methyl) the miscellaneous phenodiazines two of -2,8- The synthesis of ring [3.2.1] octyl- 3- alkene -3- amine (compound B-74)：
By N- ethyl-N-methyl -2- nitro-N- ((tetrahydrofuran -3- bases) methyl) ethylene of 1.145g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.671g (10.0mmol), slowly Deca 0.430g (5.0mmol) Butanedial.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 3.84-3.34 (m, 8H), 3.20 (q, J=12.6Hz, 1H), 3.06-2.91 (m, 4H), 2.28- (t, J=12.6Hz, the 3H) ppm of 1.85 (m, 5H), 1.85-1.30 (m, 5H), 1.17；13C NMR (100MHz, DMSO-d6)：δ 71.54,68.13,55.70,52.44,49.10,39.85,38.45,38.16,30.04,27.18,24.75,13.15ppm； HRMS(ES+)C15H26N4O3(M+H)+, value of calculation：311.2005；Measured value：311.1967.
The 1- of embodiment 20 ((6- chloropyridine -3- bases) methyl) -9- nitro -2,3,5,6,7,8- hexahydro -1H-5,8- epithios Imidazo [1,2-a] azepine -10, the synthesis of 10- double oxides (compound B-35)：
By 1- ((6- chloropyridine -3- bases) methyl) -8- nitro -1 of 1.690g (5.0mmol), 2,3,5,6,7- hexahydro -5, 20ml dichloromethane is added in 7- epithio imidazo [1,2-a] pyridines, slowly the m-chloro peroxide of Deca 1.726g (10.0mmol) Benzoic acid.After reaction 2 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling yield for 50%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=1.4Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J =7.5Hz, 1H), 4.84 (s, 2H), 4.24 (t, J=3.5Hz, 1H), 3.94 (t, J=4.5Hz, 1H), 3.21 (t, J= 6.7Hz, 1H), 3.07 (t, J=6.8Hz, 1H), 2.99 (t, J=6.7Hz, 1H), 2.89-2.73 (m, 2H), 2.62 (m, 2H), 2.21 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,138.84,130.35,123.76, 54.68,50.62,49.91,30.05,25.64ppm；HRMS(ES+)C14H15 35ClN4O4S(M+H)+, value of calculation：371.0503； Measured value：371.0147；C14H15 37ClN4O4S(M+H)+, value of calculation：373.0473；Measured value：373.0103.
The 1- of embodiment 21 ((6- chloropyridine -3- bases) methyl) -10- nitro -1,2,3,5,6,7,8,9- octahydro -5,9- rings The synthesis of imine imidazole simultaneously [1,2-a] azacyclo- pungent dilute (compound C-1)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the ammonium chloride of 0.531g (10.0mmol), slowly the glutaraldehyde of Deca 0.501g (5.0mmol).Reaction 24 After hour, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 38%.1H NMR (400MHz, DMSO- d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 4.46 (t, J=5.8Hz, 1H), 4.24 (dd, J=7.6,4.5Hz, 1H), 3.13 (m, 2H), 2.85-2.66 (m, 2H), 2.35 (s, 1H), 1.94-1.72 (m, 1H), 1.71-1.23 (m, 5H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,145.32,138.84,130.35,123.76,57.93,54.68,51.20,50.62,49.31, 34.00,33.68,17.42ppm；HRMS(ES+)C15H18 35ClN5O2(M+H)+, value of calculation：336.1149；Measured value： 336.0728；C15H18 37ClN5O2(M+H)+, value of calculation：338.1120；Measured value：338.0688.
The 1- of embodiment 22 ((6- chloropyridine -3- bases) methyl) -11- methyl isophthalic acid 0- nitro -1,2,3,5,6,7,8,9- eight Hydrogen -5, the synthesis of 9- epimino imidazo [1,2-a] azacyclo-s pungent dilute (compound C-2)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the glutaraldehyde of Deca 0.501g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 36%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 6.23 (dd, J=15.9,9.4Hz, 1H), 4.84 (s, 2H), 3.64-3.53 (m, 1H), 3.18 (m, 2H), 2.98 (t, J =13.5Hz, 1H), 2.60 (t, J=13.5Hz, 1H), 2.26 (s, 3H), 1.94-1.18 (m, 6H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,149.39,148.61,138.84,130.35,123.76,69.23,54.68, 52.84,50.62,48.79,42.32,33.63,32.04,17.62ppm；HRMS(ES+)C16H20 35ClN5O2(M+H)+, calculate Value：350.1306；Measured value：350.1078；C16H20 37ClN5O2(M+H)+, value of calculation：352.1276；Measured value： 352.1057。
The 1- of embodiment 23 ((6- chloropyridine -3- bases) methyl) -10- nitro -11- phenyl -1,2,3,5,6,7,8,9- eight Hydrogen -5, the synthesis of 9- epimino imidazo [1,2-a] azacyclo-s pungent dilute (compound C-18)：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the aniline hydrochloride of 1.290g (10.0mmol), slowly the glutaraldehyde of Deca 0.501g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains yellow powder sterling, and yield is 35%.1H NMR (400MHz, DMSO- d6) δ 8.71 (d, J=2.9Hz, 5H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 5H), 7.34 (d, J=14.9Hz, 5H), 7.30-7.13 (m, 10H), 7.01-6.86 (m, 10H), 6.86-6.72 (m, 5H), 4.99-4.88 (m, 5H), 4.84 (s, 10H), 4.76-4.66 (m, 5H), 3.17 (m, 10H), 2.86 (m, 10H), 1.97-1.55 (m, 24H), 1.53 (d, J= 1.8Hz, 1H), 1.50-1.31 (m, 5H) ppm；13CNMR (100MHz, DMSO-d6)：δ 149.48,148.70,148.63, 148.61,138.84,130.35,128.63,123.76,123.58,123.48,66.67,54.68,50.62,50.13, 48.79,33.25,32.02,17.62ppm；HRMS(ES+)C21H22 35ClN5O2(M+H)+, value of calculation：412.1462；Measured value： 412.0138；C21H22 37ClN5O2(M+H)+, value of calculation：414.1433；Measured value：414.0114.
The 1- of embodiment 24 ((6- chloropyridine -3- bases) methyl) -11- methyl isophthalic acid 0- cyano group -1,2,3,5,6,7,8,9- eight Hydrogen -5, the synthesis of 9- epimino imidazo [1,2-a] azacyclo-s pungent dilute (compound C-49)：
By 2- (1- ((6- chloropyridine -3- bases) methyl) imidazoline -2- subunits) acetonitriles of 1.170g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the glutaraldehyde of Deca 0.501g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 36%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 4.05-3.97 (m, 1H), 3.78 (dd, J=8.0,3.7Hz, 1H), 3.19 (m, 2H), 2.99 (t, J= 13.7Hz, 1H), 2.66 (t, J=13.7Hz, 1H), 2.26 (s, 3H), 1.92-1.67 (m, 1H), 1.67-1.24 (m, 5H) ppm；13C NMR (100MHz, DMSO-d6)：δ 152.65,149.48,148.61,138.84,130.35,123.76,118.72, 69.23,67.10,54.68,52.74,50.62,48.79,42.32,33.63,32.30,17.62ppm；HRMS(ES+) C17H20 35ClN5(M+H)+, value of calculation：330.1407；Measured value：330.1186；C17H20 37ClN5(M+H)+, value of calculation： 332.1378；Measured value：332.1157.
The N- of embodiment 25 ((2- diuril azoles -5- bases) methyl)-N- ethyl -2,9- dimethyl -4- nitro -2,9- diazas The synthesis of bicyclo- [3.3.1] nonyl- 3- alkene -3- amine (compound C-62)：
By N- ((2- diuril azoles -5- bases) the methyl)-N- ethyl-N-methyl -2- nitroethylenes of 1.380g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.671g (10.0mmol), slowly Deca 0.501g (5.0mmol) Glutaraldehyde.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 33%.1H NMR (400MHz, DMSO-d6) δ 6.81 (dd, J=25.7,13.1Hz, 2H), 4.51 (s, 1H), 4.37 (s, 1H), 3.64 (t, J= 10.9Hz, 1H), 3.24 (q, J=12.6Hz, 2H), 3.00 (s, 3H), 2.26 (s, 3H), 1.99-1.73 (m, 2H), 1.60- (1.11 m, 7H) ppm；13C NMR (100MHz, DMSO-d6)：δ 159.18,144.10,142.12,140.55,74.06, 52.84,48.03,45.58,42.32,38.16,32.04,31.89,17.62,13.15ppm；HRMS(ES+) C15H22 35ClN5O2S(M+H)+, value of calculation：372.1183；Measured value：372.0973；C15H22 37ClN5O2S(M+H)+, value of calculation： 374.1153；Measured value：374.0943.
The 1- of embodiment 26 ((6- chloropyridine -3- bases) methyl) -10- nitro-N-phenyl -1,2,3,5,6,7,8,9- octahydros - The synthesis of the pungent dilute -11- amine (compound C-23) of 5,9- epimino imidazo [1,2-a] azacyclo-s：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the phenylhydrazine hydrochloride of 1.440g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction After 24 hours, pale yellow powder shape sterling is filtrated to get, yield is 47%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J= 2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.38-7.17 (m, 3H), 7.13-6.97 (m, 2H), 6.88-6.74 (m, 1H), 4.84 (s, 2H), 3.27-2.97 (m, 4H), 2.66 (t, J=13.4Hz, 1H), 1.92-1.48 (m, 5H), 1.37 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,147.96,145.15,138.84, 130.35,128.97,123.76,122.18,114.39,66.32,54.68,53.74,50.62,48.79,34.45,33.02, 17.62ppm；HRMS(ES+)C21H23 35ClN6O2(M+H)+, value of calculation：427.1571；Measured value：427.1256； C21H23 37ClN6O2(M+H)+, value of calculation：429.1542；Measured value：429.1232.
The 1- of embodiment 27 ((6- chloropyridine -3- bases) methyl)-N- isopropyl -10- nitro-N-phenyl -1,2,3,5,6,7, 8,9- octahydro -5, the synthesis of the pungent dilute -11- amine (compound C-28) of 9- epimino imidazo [1,2-a] azacyclo-s：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) pyridines of 1.270g (5.0mmol) and 20ml acetonitriles are added in the 1- isopropyl -1- hydrazinobenzene hydrochloride salts of 1.861g (10.0mmol), slowly Deca 0.501g (5.0mmol) Glutaraldehyde.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 38%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=3.1Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.38- 7.19 (m, 3H), 7.19-7.03 (m, 2H), 6.97-6.83 (m, 1H), 4.84 (s, 2H), 3.22-2.91 (m, 4H), 2.60- (d, J=12.1Hz, the 6H) ppm of 2.48 (m, 1H), 1.92-1.48 (m, 5H), 1.46-1.26 (m, 1H), 1.22；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,146.29,144.31,138.84,130.35,129.34,123.76, 119.82,117.79,66.22,55.61,54.68,54.10,50.62,48.79,35.12,33.35,21.22,17.62ppm； HRMS(ES+)C24H29 35ClN6O2(M+H)+, value of calculation：469.2041；Measured value：469.1985；C24H29 37ClN6O2(M+H)+, Value of calculation：471.2011；Measured value：471.1962.
The 1- of embodiment 28 ((6- chloropyridine -3- bases) methyl) -10- nitro -1,2,3,5,6,7,8,9- octahydro -5,9- rings The synthesis of sulfur imidazo [1,2-a] azacyclo- pungent dilute (compound C-33)：
By 1- ((6- chloropyridine -3- bases) methyl) -11- methyl isophthalic acid 0- nitro -1 of 1.745g (5.0mmol), 2,3,5,6, 7,8,9- octahydro -5, the pungent dilute middle addition 20ml acetonitriles of 9- epimino imidazo [1,2-a] azacyclo-s, slowly Deca 0.852g (6.0mmol) iodomethane.After reaction 2 hours, brown solid is filtrated to get, yield is 88%.By brown solid 2.210g (4.5mmol) with the Na of 0.421g (5.4mmol)2S is soluble in water, under nitrogen protection, after reacting 2 hours at 85 DEG C, removes Solvent, column chromatography for separation obtains pale yellow powder shape sterling yield for 38%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J =2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 3.85-3.74 (m, 1H), 3.68-3.58 (m, 1H), 3.13 (m, 2H), 2.80 (m, 2H), 2.00 (m, 1H), 1.87-1.53 (m, 5H), 1.53 (s, 1H) ppm；13CNMR (100MHz, DMSO-d6)：δ 149.48,148.61,146.68,138.84,130.35, 123.76,55.53,54.68,50.62,49.91,36.68,31.69,31.66,20.42ppm；HRMS(ES+) C15H17 35ClN4O2S(M+H)+, value of calculation：353.0761；Measured value：353.0471；C15H17 37ClN4O2S(M+H)+, value of calculation： 355.0731；Measured value：355.0448.
N- ethyl -2 of embodiment 29,9- dimethyl -4- nitro-N- ((tetrahydrofuran -3- bases) methyl) the miscellaneous phenodiazines of -2,9- The synthesis of bicyclo- [3.3.1] nonyl- 3- alkene -3- amine (compound C-74)：
By N- ethyl-N-methyl -2- nitro-N- ((tetrahydrofuran -3- bases) methyl) ethylene of 1.145g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.67lg (10.0mmol), slowly Deca 0.501g (5.0mmol) Glutaraldehyde.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 34%.1H NMR (400MHz, DMSO-d6) δ 6.83 (t, J=6.3Hz, 1H), 3.84-3.73 (m, 1H), 3.62 (m, 4H), 3.51-3.41 (m, 1H), 3.35 (dd, J=12.4,6.6Hz, 1H), 3.05-2.91 (m, 5H), 2.26 (s, 3H), 2.08-1.74 (m, 4H), 1.73-1.56 (m, 1H), 1.55-1.43 (m, 2H), 1.40-1.13 (m, 5H) ppm；13C NMR (100MHz, DMSO-d6)：δ 144.96,74.06,71.54,68.13,52.84,52.44,49.10,42.32,39.85,38.16,32.04,31.89, 30.04,17.62,13.15ppm；HRMS(ES+)C16H28N4O3(M+H)+, value of calculation：325.2161；Measured value：325.1874.
The 1- of embodiment 30 ((6- chloropyridine -3- bases) methyl) -10- nitro -1,2,3,5,6,7,8,9- octahydro -5,9- rings The synthesis of pungent dilute -11, the 11- double oxides (compound C-35) of sulfur imidazo [1,2-a] azacyclo-：
By 1- ((6- chloropyridine -3- bases) methyl) -10- nitro -1 of 1.760g (5.0mmol), 2,3,5,6,7,8,9- eight Hydrogen -5, the pungent dilute middle addition 20ml dichloromethane of 9- epithio imidazo [1,2-a] azacyclo-s, slowly Deca 1.726g (10.0mmol) Metachloroperbenzoic acid.After reaction 2 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling yield and is 50%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 4.24 (t, J=6.1Hz, 1H), 3.89 (t, J=6.5Hz, 1H), 3.19 (dd, J=19.9,7.4Hz, 1H), 3.14-2.95 (m, 2H), 2.73 (dd, J=19.9,7.4Hz, 1H), 2.25-1.57 (m, 6H) ppm；13C NMR (100MHz, DMSO-d6)：δ 160.00,149.48,148.61,138.84,130.35,123.76, 54.68,50.62,49.91,28.51,23.74,20.42ppm；HRMS(ES+)C15H17 35ClN4O4S(M+H)+, value of calculation： 385.0659；Measured value：385.0468；C15H17 37ClN4O4S(M+H)+, value of calculation：387.0630；Measured value：387.0424.
The N- of embodiment 31 ((6- chloropyridine -3- bases) methyl)-N- ethyl -2,6- dimethyl -4- nitro -2,6- diazas The synthesis of bicyclo- [3.1.1] hept- 3- alkene -3- amine (compound A-33)：
By N- ((6- chloropyridine -3- bases) the methyl)-N- ethyl-N-methyl -2- nitroethylenes of 1.350g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.671g (10.0mmol), slowly Deca 0.360g (5.0mmol) Malonaldehyde.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 36%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=1.4Hz, 1H), 8.05 (dd, J=7.6,1.5Hz, 1H), 7.34 (d, J= 7.5Hz, 1H), 4.84 (s, 2H), 3.23 (m, 3H), 3.06-2.98 (m, 4H), 2.36 (m, 1H), 2.26 (s, 3H), 1.82 (m, 1H), 1.17 (t, J=6.3Hz, 3H) ppm；13CNMR (100MHz, DMSO-d6)：δ 156.28,149.48,148.61, 138.84,130.35,123.76,55.24,47.45,41.67,39.81,31.94,13.15ppm；HRMS(ES+) C15H20 35ClN5O2(M+H)+, value of calculation：338.1306；Measured value：338.1126；C15H20 37ClN5O2(M+H)+, value of calculation： 340.1276；Measured value：340.1102.
The N- of embodiment 32 ((6- chloropyridine -3- bases) methyl)-N- ethyl -2,8- dimethyl -4- nitro -2,8- diazas The synthesis of bicyclo- [3.2.1] octyl- 3- alkene -3- amine (compound B-44)：
By N- ((6- chloropyridine -3- bases) the methyl)-N- ethyl-N-methyl -2- nitroethylenes of 1.350g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.671g (10.0mmol), slowly Deca 0.430g (5.0mmol) Butanedial.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=3.1Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J =14.9Hz, 1H), 4.84 (s, 2H), 3.55-3.42 (m, 2H), 3.24 (m, 2H), 3.00 (s, 3H), 2.26 (s, 3H), 1.80-1.59 (m, 1H), 1.54-1.11 (m, 6H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61, 138.84,130.35,123.76,55.70,55.24,47.45,38.45,38.16,27.18,24.75,13.15ppm；HRMS (ES+)C16H22 35ClN5O2(M+H)+, value of calculation：352.1462；Measured value：352.1233；C16H22 37ClN5O2(M+H)+, calculate Value：354.1433；Measured value：354.1212.
The N- of embodiment 33 ((6- chloropyridine -3- bases) methyl)-N- ethyl -2,9- dimethyl -4- nitro -2,9- diazas The synthesis of bicyclo- [3.3.1] nonyl- 3- alkene -3- amine (compound C-44)：
By N- ((6- chloropyridine -3- bases) the methyl)-N- ethyl-N-methyl -2- nitroethylenes of 1.350g (5.0mmol) - 20ml acetonitriles are added in the methylamine hydrochloride of 1,1- diamidogen and 0.671g (10.0mmol), slowly Deca 0.501g (5.0mmol) Glutaraldehyde.After reaction 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 33%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J =14.9Hz, 1H), 6.84 (t, J=12.7Hz, 1H), 4.84 (s, 2H), 3.74 (t, J=11.1Hz, 1H), 3.24 (m, 2H), 3.00 (s, 3H), 2.26 (s, 3H), 1.99-1.76 (m, 2H), 1.60-1.41 (m, 2H), 1.41-1.11 (m, 5H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,144.32,138.84,130.35,123.76,74.06,55.24, 52.84,47.45,42.32,38.16,32.04,31.89,17.62,13.15ppm；HRMS(ES+)C17H24 35ClN5O2(M+H )+, value of calculation：366.1619；Measured value：366.1486；C17H24 37ClN5O2(M+H)+, value of calculation：368.1589；Measured value： 368.1462。
9- methyl -8- nitro-the 1- of embodiment 34 ((tetrahydrofuran -3- bases) methyl) -1,2,3,5,6,7- hexahydro -5,7- The synthesis of epimino imidazo [1,2-a] pyridine (compound A-71)：
By 2- (Nitromethylene) -1- ((tetrahydrofuran -3- bases) methyl) imidazolines of 1.065g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the malonaldehyde of Deca 0.360g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 4.09-3.95 (m, 1H), 3.85-3.53 (m, 3H), 3.53-3.38 (m, 1H), 3.28 (m, 2H), 3.10-2.91 (m, 3H), 2.83 (dd, J=19.6,7.3Hz, 1H), 2.42 (m, 2H), 2.26 (s, 3H), 2.06-1.51 (m, 4H) ppm；13C NMR (100MHz, DMSO-d6)：δ 152.31,71.54,68.13,53.05,51.69,49.95,41.67,39.85,31.15, 30.04ppm；HRMS(ES+)C13H20N4O3(M+H)+, value of calculation：280.1535；Measured value：280.1273.
10- methyl -9- nitro -1- ((tetrahydrofuran -3- bases) methyl) -2,3,5,6,7, the 8- hexahydro -1H- of embodiment 35 The synthesis of 5,8- epimino imidazo [1,2-a] azepines (compound B-80)：
By 2- (Nitromethylene) -1- ((tetrahydrofuran -3- bases) methyl) imidazolines of 1.065g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 37%.1H NMR (400MHz, DMSO-d6) δ 3.86-3.38 (m, 6H), 3.31-3.19 (m, 2H), 3.02 (t, J=13.7Hz, 1H), 2.88 (t, J= 13.7Hz, 1H), 2.76-2.54 (m, 2H), 2.48-2.10 (m, 4H), 1.93 (m, 1H), 1.79-1.28 (m, 5H) ppm；13C NMR (100MHz, DMSO-d6)：δ 71.54,68.13,55.70,53.05,51.69,48.79,39.85,38.45,30.04, 27.89,24.75ppm；HRMS(ES+)C14H22N4O3(M+H)+, value of calculation：295.1692；Measured value：295.1473.
The 11- methyl isophthalic acid 0- nitro -1- of embodiment 36 ((tetrahydrofuran -3- bases) methyl) -1,2,3,5,6,7,8,9- eight Hydrogen -5, the synthesis of 9- epimino imidazo [1,2-a] azepine cyclo-octene (compound C-80)：
By 2- (Nitromethylene) -1- ((tetrahydrofuran -3- bases) methyl) imidazolines of 1.065g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the glutaraldehyde of Deca 0.501g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 34%.1H NMR (400MHz, DMSO-d6) δ 6.30 (dd, J=15.9,9.3Hz, 1H), 3.84-3.35 (m, 6H), 3.23-2.90 (m, 4H), 2.58 (dd, J =20.0,6.9Hz, 1H), 2.43-2.23 (m, 4H), 2.03-1.21 (m, 8H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.23,71.54,69.23,68.13,53.05,52.84,51.69,48.79,42.32,39.85,33.63,32.04, 30.04,17.62ppm；HRMS(ES+)C15H24N4O3(M+H)+, value of calculation：309.1848；Measured value：309.0128.
The chloro- 5- of the 2- of embodiment 37 ((9- methyl -8- nitro -2,3,6,7- tetrahydrochysene -5,7- epimino imidazos [1,2-a] Pyridine -1 (5H)-yl) methyl) thiazole (compound A-57) synthesis：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) thiazoles of 1.300g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the malonaldehyde of Deca 0.360g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 35%.1H NMR (400MHz, DMSO-d6) δ 6.76 (s, 1H), 5.26 (s, 1H), 4.26 (s, 1H), 3.44-3.22 (m, 4H), 3.05 (t, J=13.7Hz, 1H), (m, the 1H) ppm of 2.91 (t, J=13.7Hz, 1H), 2.45 (m, 1H), 2.26 (s, 3H), 1.82；13C NMR (100MHz, DMSO-d6)：δ 159.18,152.72,142.12,140.55,51.50,49.95,47.97,41.67,31.15ppm；HRMS (ES+)C12H14 35ClN5O2S(M+H)+, value of calculation：328.0557；Measured value：328.0287；C12H14 37ClN5O2S(M+H)+, meter Calculation value：330.0527；Measured value：330.0257.
The chloro- 5- of the 2- of embodiment 38 ((10- methyl -9- nitro -2,3,5,6,7,8- hexahydro -1H-5,8- epimino imidazos [1,2-a] azepine -1- bases) methyl) thiazole (compound B-68) synthesis：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) thiazoles of 1.300g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 39%.1H NMR (400MHz, DMSO-d6) δ 6.76 (s, 1H), 5.06 (s, 1H), 4.56 (s, 1H), 3.76-3.67 (m, 1H), 3.40-3.11 (m, 3H), 2.87 (t, J=13.9Hz, 1H), 2.75 (t, J=13.9Hz, 1H), 2.26 (s, 3H), 1.80-1.30 (m, 4H) ppm；13C NMR (100MHz, DMSO-d6)：δ 159.18,142.12,140.55,55.70,51.50,48.79,47.97,38.45, 27.89,24.75ppm；HRMS(ES+)C13H16 35ClN5O2S(M+H)+, value of calculation：342.0713；Measured value：342.0568； C13H16 35ClN5O2S(M+H)+, value of calculation：344.0684；Measured value：344.0549.
The chloro- 5- of the 2- of embodiment 39 ((11- methyl isophthalic acid 0- nitro -2,3,6,7,8,9- hexahydro -5,9- epimino imidazos [1,2-a] azacyclo- octene-1 (5H)-yl) methyl) thiazole (compound C-68) synthesis：
By the chloro- 5- of 2- ((2- (Nitromethylene) imidazoline -1- bases) methyl) thiazoles of 1.300g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the glutaraldehyde of Deca 0.501g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 34%.1H NMR (400MHz, DMSO-d6) δ 6.76 (s, 1H), 5.15 (s, 1H), 4.17 (s, 1H), 3.80 (dd, J=7.4,4.4Hz, 1H), 3.52 (dd, J =8.4,4.4Hz, 1H), 3.24 (m, 2H), 2.93 (t, J=14.1Hz, 1H), 2.71 (t, J=14.1Hz, 1H), 2.26 (s, 3H), 2.05-1.72 (m, 1H), 1.71-1.30 (m, 5H) ppm；13CNMR (100MHz, DMSO-d6)：δ 159.18,148.65, 142.12,140.55,69.23,52.84,51.50,48.79,47.97,42.32,33.63,32.04,17.62ppm；HRMS (ES+)C14H18 35ClN5O2S(M+H)+, value of calculation：356.0870；Measured value：356.0687；C14H18 37ClN5O2S(M+H)+, meter Calculation value：358.0840；Measured value：358.0657.
The 1- of embodiment 40 ((6- chloropyridine -3- bases) methyl) -10- methyl -9- nitro -2,3,4,6,7,8- hexahydro -1H- The synthesis of 6,8- epimino pyrido [1,2-a] pyrimidines (compound A-44)：
By 1- ((6- chloropyridine -3- bases) methyl) -2- (Nitromethylene) hexahydropyrimidines of 1.340g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the malonaldehyde of Deca 0.360g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 36%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 3.22 (t, J=10.8Hz, 2H), 2.26 (s, 3H), 1.93 (p, J=10.7Hz, 2H), 1.05 (t, J =10.6Hz, 2H), 1.00 (m, 4H) ppm；13C NMR (100MHz, DMSO-d6)：δ 164.01,149.48,148.61, 138.84,130.35,123.76,56.61,48.59,48.31,41.67,31.15,21.83ppm；HRMS(ES+) C15H18 35ClN5O2(M+H)+, value of calculation：336.1149；Measured value：336.0856；C15H18 37ClN5O2(M+H)+, value of calculation： 338.1120；Measured value：338.0832.
The 1- of embodiment 41 ((6- chloropyridine -3- bases) methyl) -11- methyl isophthalic acid 0- nitro -1,2,3,4,6,7,8,9- eight Hydrogen -6, the synthesis of 9- epimino pyrimido [1,2-a] azepines (compound B-56)：
By 1- ((6- chloropyridine -3- bases) methyl) -2- (Nitromethylene) hexahydropyrimidines of 1.340g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the butanedial of Deca 0.430g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 39%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 3.37-3.17 (m, 4H), 2.77 (m, 2H), 2.26 (s, 3H), 1.92 (m, 2H), 1.76-1.28 (m, 3H), 1.06-0.85 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 157.56,149.48,148.61,138.84, 130.35,123.76,56.61,55.70,48.59,46.16,38.45,27.89,24.75,21.83ppm；HRMS(ES+) C16H20 35ClN5O2(M+H)+, value of calculation：350.1306；Measured value：350.1046；C16H20 37ClN5O2(M+H)+, value of calculation： 352.1276；Measured value：352.1022.
The 1- of embodiment 42 ((6- chloropyridine -3- bases) methyl) -12- methyl isophthalic acid 1- nitro -2,3,4,6,7,8,9,10- eight The synthesis of hydrogen -1H-6,10- epimino pyrimido [1,2-a] azacyclo- pungent dilute (compound C-56)：
By 1- ((6- chloropyridine -3- bases) methyl) -2- (Nitromethylene) hexahydropyrimidines of 1.340g (5.0mmol) and 20ml acetonitriles are added in the methylamine hydrochloride of 0.671g (10.0mmol), slowly the glutaraldehyde of Deca 0.501g (5.0mmol).Reaction After 24 hours, solvent is removed, column chromatography for separation obtains pale yellow powder shape sterling, and yield is 38%.1H NMR (400MHz, DMSO-d6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J1=8.0Hz, J2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 6.54-6.42 (m, 1H), 4.84 (s, 2H), 3.39-3.27 (m, 1H), 3.22 (t, J=10.8Hz, 2H), 2.89 (t, J =10.7Hz, 1H), 2.65 (t, J=10.8Hz, 1H), 2.26 (s, 3H), 2.01-1.49 (m, 7H), 1.49-1.30 (m, 1H) ppm；13C NMR (100MHz, DMSO-d6)：δ 149.48,148.61,138.84,130.35,123.76,72.06,56.61, 52.84,48.59,46.16,42.32,33.63,32.04,21.83,17.62ppm；HRMS(ES+)C17H22 35ClN5O2(M+H )+, value of calculation：364.1462；Measured value：364.1203；C17H22 37ClN5O2(M+H)+, value of calculation：366.1433；Measured value： 366.1179。
The preparation of other compounds in the table 1～3 of embodiment 43
Repeat the method in embodiment 1-42, difference is using corresponding initiation material in table 1～3, so as to be obtained Other compounds shown in table 1～3.
Embodiment 44：The insecticidal activity test of the compounds of this invention
(1) to the insecticidal activity of aphid：
Aphid belongs to homoptera pest, is a kind of common crop pests with piercing mouth parts.With bean aphid (Aphis Craccivora) it is test object, is tested using infusion process.
Operating process：The various samples of precise, are separately added into DMF and are configured to 10g/L mother solutions, real The concentration of 500ug/mL is diluted to when testing with the aqueous solution of the X-100 of Triton containing 0.2mL/L.Treat aptery adult aphid in bean sprout On stably suck after, together with bean sprout immerse concentration be 500ug/mL medicinal liquid in, after 5s take out, it is unnecessary to be sucked with absorbent paper Medicinal liquid, moves in clean vessel and is raised in 23 DEG C of constant temperature.3 repetitions are set per concentration, matched group is the X- of Triton containing 0.2mL/L 100 aqueous solution.After processing 24 hours, the dead borer population of statistics examination aphid, and mortality rate (%) is calculated, the results are shown in Table 1～table 3.
Mortality rate (%)=(control borer population living-process work borer population)/control borer population × 100% living
(2)：Insecticidal activity to mythimna separata
Using leaching leaf feeding method.Fresh maize leaf impregnates in above-mentioned solution 3 seconds, then airing at room temperature, Take food for test worm, the mortality rate (%) (formula is ibid) of test worm is checked and calculated after 24h, often process and use 10 test worms, if 3 weights It is multiple.Blank is made with clear water process, and calculates mortality rate (%).The results are shown in Table 1～table 3.
Formula A Formula B formula c
Table 1 has the representation compound activity list of formula A structures
Table 2 has the representation compound activity list of Formula B structure
Table 3 has the representation compound activity list of formula C-structure
The preparation of insecticides of the embodiment 45. containing the compounds of this invention
(a) oleaginous suspension
Prepare following components in proportion：25% (percentage by weight, similarly hereinafter) compound A-1～A-87, B-1～B-95, C-1 Any one compound in～C-95；The oleate of 5% polyoxyethylene sorbitol six；70% higher aliphatic hydrocarbon ils.Each component is existed Grind together in sand mill, till solid particle is down to below about 5 microns.The thick suspension of gained can be used directly, but Also can use after emulsifying in water.
(b) water slurry
Prepare following components in proportion：Any one change in 25% compound A-1～A-87, B-1～B-95, C-1～C-95 Compound；3% hydration Attagel (hydrate attapulgit)；10% calcium lignosulfonate；0.5% sodium dihydrogen phosphate； 61.5% water.Each component is ground together in ball mill, till solid particle is down to below about 10 microns.The aqueous suspension Liquid can be used directly.
(c) bait formulation
Prepare following components in proportion：It is arbitrary in 0.1-10% compounds A-1～A-87, B-1～B-95, C-1～C-95 Plant compound；80% Semen Tritici aestivi flour；19.9-10% molasses.These components are thoroughly mixed, bait shape is formed on demand.It is edible The place that sanitary insect pest is infected, such as such as household or industrial site, kitchen, hospital or shop or family can be distributed to bait Exterior domain, with by being orally ingested come pest control.
The all documents referred in the present invention are all incorporated as in this application reference, independent just as each document It is incorporated as with reference to such.In addition, it is to be understood that after the above-mentioned teachings for having read the present invention, those skilled in the art can To make various changes or modifications to the present invention, these equivalent form of values equally fall within the model that the application appended claims are limited Enclose.

Claims (25)

1. a kind of optical isomer of compound with structure shown in formula 1, or the compound, cis-trans-isomer or pesticide Acceptable salt on：
In formula：
R1For unsubstituted or substituted pyridine radicals, thiazolyl, tetrahydrofuran base, wherein, be substituted by being selected from the group Or multiple substituent groups：Halogen, C1–4Haloalkyl；
R2And R3It is each independently saturation or unsaturation C1-8Alkyl；Or
R2And R3Collectively form-CH2-CH2- or-CH2-CH2-CH2-,；
X independently is N；
Wherein, as X=N, R4It independently is H, saturation or unsaturation C1-8Alkyl, C1–8Haloalkyl, sulfonyl；Or be selected from One kind in phenyl ring, naphthalene nucleus, furan, oxazoles, wherein above-mentioned group is substituent group that is unsubstituted or being selected from the following group being replaced： Halogen, nitro, saturation or unsaturation C1-4Alkyl；
Or as X=N, R4- YR can also independently beaRbStructure, wherein Y independently are N, SO or SO2；
RaAnd RbIt is each independently H, saturation or unsaturation C1-8Alkyl；Or for phenyl ring, or above-mentioned phenyl ring is optionally by halogen Element, nitro, saturation or unsaturation C1-4Alkyl is replaced；
M is 1 or 3, and as m=1 or 3, compound respectively shown in formula A, C；
It is above-mentioned it is various in, R5、R6、R7、R10、R11And R12It is each independently H, halogen, saturation or unsaturation C1-8Alkyl；
Z is nitro, cyano group, trifluoroacetyl group.
2. can in the optical isomer of compound as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science The salt of acceptance, it is characterised in that the saturation or unsaturation C1-8Alkyl is pi-allyl.
3. can in the optical isomer of compound as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science The salt of acceptance, it is characterised in that R1It is selected from：The pyridine radicals of halo, the thiazolyl of halo, the tetrahydrofuran base of halo.
4. can in the optical isomer of compound as claimed in claim 3 or the compound, cis-trans-isomer or Pesticide Science The salt of acceptance, it is characterised in that the halo is chloro.
5. can in the optical isomer of compound as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science The salt of acceptance, it is characterised in that R2、R3Collectively form-CH2-CH2- or-CH2-CH2-CH2。
6. can in the optical isomer of compound as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science The salt of acceptance, it is characterised in that R2And R3For hydrogen or saturation or unsaturation C1-8Alkyl.
7. can in the optical isomer of compound as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science The salt of acceptance, it is characterised in that R2And R3It is selected from the group：Methyl or ethyl.
8. can in the optical isomer of compound as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science The salt of acceptance, it is characterised in that as X=N, R4It independently is H, saturation or unsaturation C1-8Alkyl；Or selected from phenyl ring, naphthalene Ring, the one kind in furan ， oxazoles, optionally by halogen, nitro is replaced above-mentioned group.
9. can in the optical isomer of compound as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science The salt of acceptance, it is characterised in that as X=N, R4- YR can also independently beaRbStructure, wherein Y independently are N, SO or SO2；
RaAnd RbIt is each independently H, saturation or unsaturation C1-8Alkyl.
10. in the optical isomer of compound as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science Acceptable salt, it is characterised in that as X=N, R4It independently is H, saturation or unsaturation C1-8Alkyl, or selected from phenyl ring.
In the optical isomer of 11. compounds as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science Acceptable salt, it is characterised in that as X=N, R4For H, methyl, ethyl, phenyl, Sulfonyl.
In the optical isomer of 12. compounds as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science Acceptable salt, it is characterised in that the optical isomer of the compound or the compound, cis-trans-isomer or Pesticide Science Upper acceptable salt is selected from the group：
In the optical isomer of 13. compounds as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science Acceptable salt, it is characterised in that m is 1 or 3, and as m=1, Its In, it is above-mentioned it is various in, R7、R10、R11And R12As defined in claim 1.
In the optical isomer of 14. compounds as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science Acceptable salt, it is characterised in that R5、R6、R7、R10、R11And R12It is each independently H, halogen, saturation or unsaturation C1-8Hydrocarbon Base.
In the optical isomer of 15. compounds as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science Acceptable salt, it is characterised in that R5、R6、R7、R10、R11And R12It is each independently hydrogen, methyl, chlorine, bromine.
In the optical isomer of 16. compounds as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science Acceptable salt, it is characterised in that Z is nitro, cyano group, trifluoroacetyl group.
In the optical isomer of 17. compounds as claimed in claim 1 or the compound, cis-trans-isomer or Pesticide Science Acceptable salt, it is characterised in that Z is nitro.
A kind of 18. agriculturally useful compositions, it is included：
Compound, its optical isomer any one of claim 1-17 of (a) 0.0001-99.99 weight %, along anti- Acceptable salt or combinations thereof in isomer or Pesticide Science；And
Acceptable carrier and/or excipient in (b) Pesticide Science.
19. agriculturally useful compositions as claimed in claim 18, it is characterised in that the agriculturally useful compositions also include other active matters Matter, described other active substances are selected from：Insecticide, bait formulation, antibacterial, acaricide or growth control agent.
The purposes of 20. agriculturally useful compositions as claimed in claim 18, it is characterised in that kill or prevent agricultural evil for preparing The pesticide of the insect of worm, sanitary insect pest and harm animal health；Or be used to killing or preventing agricultural pests, health evil as preparing Worm and the insecticides of harm animal health.
A kind of 21. methods for preparing agriculturally useful compositions described in claim 18, it is characterised in that including step：Will by (a) right Ask in compound any one of 1-17, its optical isomer, cis-trans-isomer or Pesticide Science acceptable salt or it Combination；Mixed with acceptable carrier and/or excipient in (b) Pesticide Science, so as to form agriculturally useful compositions.
A kind of 22. parasite killing and/or insect-prevention method, it is characterised in that include the compound described in any one of claim 1-17 Or the compositionss described in claim 18 put on plant, animal body, the soil around it that be subjected to or can suffer from insect pest Or in environment.
The optical isomer of a kind of 23. compounds as claimed in claim 1 or the compound, cis-trans-isomer or pesticide The purposes of acceptable salt or combinations thereof on, it is characterised in that for prepare for kill or prevent agricultural pests, The insecticides of sanitary insect pest and harm animal health.
Optical isomer, the cis-trans-isomer of 24. compounds as any one of claim 1-17 or the compound Or in Pesticide Science acceptable salt preparation method, it is characterised in that as X=N, including step：
In polar solvent, in the presence of the acid of catalytic amount, by compound W and R4NH2Inorganic acid salt or acylate, respectively Reacted with formula A0 compound or formula C0 compound, so as to obtain formula A1 compound or formula C1 compound respectively；
It is above-mentioned it is various in, R1、R2、R3、R4、R5、R6、R7、R10、R11、R12It is as defined in claim 1 with Z.
25. preparation methoies as claimed in claim 24, it is characterised in that the acid of the catalytic amount is the one kind in being selected from the group Or various Bronsted acids or lewis acid：Hydrochloric acid, acetic acid, sodium dihydrogen phosphate, p-methyl benzenesulfonic acid, trifluoroacetic acid, boron trifluoride, trichlorine Change aluminum, ferric chloride, magnesium chloride, cobaltous chloride, strontium chloride, Palladous chloride. or Nickel dichloride..
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