CN103242323A - 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 PDFInfo
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- CN103242323A CN103242323A CN2012100258565A CN201210025856A CN103242323A CN 103242323 A CN103242323 A CN 103242323A CN 2012100258565 A CN2012100258565 A CN 2012100258565A CN 201210025856 A CN201210025856 A CN 201210025856A CN 103242323 A CN103242323 A CN 103242323A
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- 0 *CN(*)C1=C(*)C(*)(C(*C2)C3*)*2C3(*)N1* Chemical compound *CN(*)C1=C(*)C(*)(C(*C2)C3*)*2C3(*)N1* 0.000 description 4
- VMTHRRYIEUFJJU-BYMHUXMISA-N CC(CCC1N(CCN2Cc(cc3)cnc3Cl)C2=C(C23)[N+]([O-])=O)[C@@]22[N]13N2c1ccccc1 Chemical compound CC(CCC1N(CCN2Cc(cc3)cnc3Cl)C2=C(C23)[N+]([O-])=O)[C@@]22[N]13N2c1ccccc1 VMTHRRYIEUFJJU-BYMHUXMISA-N 0.000 description 1
- AWZKZPGAZRQOQO-FMIVXFBMSA-N Cc1ccc(CN(CCCN2)/C2=C/[N+]([O-])=O)cn1 Chemical compound Cc1ccc(CN(CCCN2)/C2=C/[N+]([O-])=O)cn1 AWZKZPGAZRQOQO-FMIVXFBMSA-N 0.000 description 1
- ALNDHUQPXHHNON-JXMROGBWSA-N [O-][N+](/C=C1/N(Cc(cn2)ccc2Cl)CCN1)=O Chemical compound [O-][N+](/C=C1/N(Cc(cn2)ccc2Cl)CCN1)=O ALNDHUQPXHHNON-JXMROGBWSA-N 0.000 description 1
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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
Technical field
The present invention relates to a kind of nitrogenous (sulphur) bridged ring class neonicotine sterilant, and its preparation method and application.
Technical background
20th century the mid-80 Beyer Co., Ltd (Bayer) develop first anabasine insecticide Provado, become one of the most successful novel pesticide, be that the anabasine insecticide of representative is because of the insecticidal activity height with the Provado, insecticidal spectrum is wide, low to Mammals and hydrocoles toxicity, and good system's rerum natura and suitable field stability and environment friendly are arranged, become the important hot fields of novel pesticide initiative.Developed a series of nicotinic insecticides such as thiophene worm quinoline, thiophene worm amine, thiophene worm piperazine, acetamiprid, Ti304, MTI-446 afterwards again in succession.Anabasine insecticide is because of the insecticidal activity height, and insecticidal spectrum is wide, and is low to Mammals and hydrocoles toxicity, and good system's rerum natura and suitable field stability are arranged, and become the important hot fields of agricultural chemicals initiative.
But because the comparatively serious resistance problem that causes of the excessive frequent use of Provado and because the cross resistance between the neonicotine sterilant that structural similarity is brought, limited such application of compound to a certain extent, become the major issue of this compounds development of restriction, anabasine insecticide is mainly efficient to Homoptera and coleopteran pest simultaneously, and the insecticidal spectrum of its relative narrower has also limited the medication selectivity of pest control aspect.
Therefore, carry out structure of modification to having highly active Nitromethylene compounds, obtain new, compound more efficiently, solve the resistance problem of anabasine insecticide, enlarge insecticidal spectrum, making it be applied to sterilant is the technical issues that need to address of the present invention.
Summary of the invention
The invention provides new efficient pesticides, improved the insecticidal activity of anabasine compound, enlarged insecticidal spectrum, solved problems of the prior art.
The object of the invention is, compound of a class high-efficiency prevention and control insect and preparation method thereof is provided.
Another object of the present invention is not to be subjected to attack of insect and invasion that protection is provided for the crop with results in the growth.
The present invention introduces nitrogenous (sulphur) bridged ring at the Nitromethylene of existing nitro-methylene-type neonicotine sterilant, has synthesized a kind of novel anabasine compound, and this compounds has significant insecticidal activity, and insecticidal spectrum is wide.
In a first aspect of the present invention, a kind of compound with structure shown in the general formula 1 is provided, or acceptable salt on the optical isomer of described compound, cis-trans-isomer or the Pesticide Science:
General formula 1
In the formula:
R
1Be five yuan or hexa-member heterocycle base of nitrogenous, oxygen and/or sulphur, nitrogenous, the oxygen of halo and/or five yuan or hexa-member heterocycle base of sulphur perhaps replace or unsubstituted phenyl, and wherein, described substituting group is to be selected from down one or more in organizing: halogen, C
1-4Haloalkyl or C
1-4Halogenated alkoxy;
R
2And R
3Be H independently of one another, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl is perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, saturated or unsaturated C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps
R
2And R
3Common formation-CH
2-CH
2-,-CH
2-CH
2-CH
2-or-CH
2-MRc-CH
2-, M is the heteroatoms that is selected from down group: N in the formula, O or S, and Rc is the substituting group on the heteroatoms, is selected from H, saturated or unsaturated C
1-8Alkyl or alkoxyl group, allyl group, benzyl, phenyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl is perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl;
X is N, S, SO or SO independently
2
Wherein, when X=N, R
4Be H independently, saturated or unsaturated C
1-8Alkyl, C
1-8Haloalkyl, alkylsulfonyl, allyl group, benzyl, saturated or unsaturated C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl; Perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps be selected from a kind of in phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furans, thiophene, oxazole, quinoline, nitrogenous (oxygen, the sulphur) heteroaromatic of benzo (mixing) ring, wherein said fragrance (mixing) ring is unsubstituted or is selected from down the substituting group of organizing and replaces: halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, dimethylin, saturated or unsaturated C
1-4Alkyl, C
1-4Alkoxyl group, C
1-4Haloalkyl, or C
1-4Alkyl-carbonyl;
Perhaps when X=N, R
4Also can be independently-YR
aR
bStructure, wherein Y is N, S, SO or SO independently
2
R
aAnd R
bBe H independently of one another, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl; Perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps be selected from phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furans, a kind of in the thiophene ， oxazole, quinoline fragrance (mixing) ring, or above-mentioned fragrance (mix) encircles optionally by halogen itrile group, nitro, hydroxyl, carboxyl, saturated or unsaturated C
1-4Alkyl, C
1-4Alkoxyl group, C
1-4Alkyl-carbonyl, methylamino, or C
1-4Haloalkyl replaces;
Perhaps R
aAnd R
bCommon formation-CH
2-CH
2-,-CH
2-CH
2-CH
2-or-CH
2-MRc-CH
2-, M is the heteroatoms that is selected from down group in the formula: N, O or S; Rc is the substituting group on the heteroatoms, is selected from H, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, phenyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl is perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps
Work as X=S, SO, or SO
2The time, R
4Do not exist;
M is 1～3 integer, and works as m=1,2, or 3 o'clock, be respectively compound shown in general formula A, B, the C;
m＝1 m＝2 m＝3
General formula A Formula B general formula c
In above-mentioned various (general formula 1, A, B and C), R
5, R
6, R
7, R
8, R
9, R
10, R
11And R
12Be H independently of one another, halogen, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, saturated or unsaturated C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxy carbonyl, carbobenzoxy, C
2-6The alkynyl carbonyl, C
2-3Alkenyl carbonyl, C
3-6Naphthene base carbonyl, aromaticacyl radical; Perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The aromaticacyl radical that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; C
1-8Saturated or unsaturated alkoxyl group, halo C
1-8Saturated or unsaturated alkoxyl group, C
1-8Alkyl-ester group (RCOO-), C
1-8Alkyl-sulphonyl ester group or fluoroform sulfonyl ester; Perhaps be phenyl ring, pyridine, naphthalene nucleus, furans or the quinoline that does not replace or replace, described substituting group is selected from down group: halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, dimethylin, saturated or unsaturated C
1-8Alkyl, C
1-8Alkoxyl group, C
1-8Haloalkyl, C
1-8Alkyl-carbonyl;
Z is nitro, cyano group, ester group, aldehyde radical, carboxyl, trifluoromethyl, trifluoroacetyl group, or trifyl.
In another preference, R
1Be selected from: the pyridyl, thiazolyl, pyrimidyl, tetrahydrofuran base, oxazolyl or its halides that replace or replace, wherein, described substituting group is to be selected from down one or more in organizing: halogen, C
1-4Haloalkyl or C
1-4Halogenated alkoxy.
In another preference, R
1Be selected from: the pyrimidyl of the pyridyl of halo, the thiazolyl of halo, halo, the tetrahydrofuran base of halo or halo De oxazolyl; More preferably described halides is the chloro thing.
In another preference, R
2, R
3Common formation-CH
2-CH
2-,-CH
2-CH
2-CH
2-or-CH
2-MRc-CH
2-, wherein M is the heteroatoms that is selected from down group: N, O or S; Rc is the saturated or unsaturated C on the heteroatoms
1-8Alkyl or alkoxyl group.
In another preference, R
2And R
3Be the saturated or unsaturated C of hydrogen
1-8Alkyl, perhaps R
2And R
3Common formation-CH
2-CH
2-or-CH
2-CH
2-CH
2-.
In another preference, R
2And R
3Be hydrogen or C
1-8Alkyl, preferred hydrogen, methyl or ethyl, perhaps R
2And R
3Common formation-CH
2-CH
2-or-CH
2-CH
2-CH
2-.
In another preference, X is preferably N, S, SO, or SO
2
In another preference, when X=N, R
4Be H independently, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, saturated or unsaturated C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl; Perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps be selected from phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furans, a kind of in the thiophene ， oxazole, quinoline fragrance (mixing) ring, above-mentioned fragrance (mixing) encircles optionally by halogen, itrile group, carboxyl, nitro, hydroxyl, methylamino, C
1-4Haloalkyl replaces.
In another preference, when X=N, R
4Also can be independently-YR
aR
bStructure, wherein Y is N, S, SO or SO independently
2R
aAnd R
bBe H independently of one another, saturated or unsaturated C
1-8Alkyl, allyl group, phenyl, benzyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, or carbobenzoxy; Perhaps R
aAnd R
bCommon formation-CH
2-CH
2-,-CH
2-CH
2-CH
2-or-CH
2-MRc-CH
2-, M is the heteroatoms that is selected from down group in the formula: N, O or S; Rc is the substituting group on the heteroatoms, is selected from H, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, phenyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, or carbobenzoxy.
In another preference, when X=N, R
4Be H independently, saturated or unsaturated C
1-8Alkyl perhaps is selected from phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furans, a kind of in the thiophene ， oxazole, the fragrance of quinoline (mixing) ring; In another preference, when X=N, R
4Be preferably H, methyl, ethyl, phenyl,
Alkylsulfonyl,
In another preference, work as X=S, SO, or SO
2The time, R
4Do not exist.
In another preference, m is 1～3 integer, and when m=1,
During m=2,
During m=3,
Wherein, above-mentioned various in, R
7, R
8, R
9, R
10, R
11, and R
12Such as in the first aspect present invention definition.
In another preference, R
5, R
6, R
7, R
8, R
9, R
10, R
11And R
12Be H independently of one another, halogen, saturated or unsaturated C
1-8Alkyl, C
1-8Saturated or unsaturated alkoxyl group, halo C
1-8Saturated or unsaturated alkoxyl group, C
1-8Alkyl-ester group (RCOO-), C
1-8Alkyl-sulphonyl ester group or fluoroform sulfonyl ester; Perhaps be phenyl ring, pyridine, naphthalene nucleus, furans or the quinoline of replacement, described substituting group is selected from down group: halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, dimethylin, saturated or unsaturated C
1-8Alkyl, C
1-8Alkoxyl group, C
1-8Haloalkyl, C
1-8Alkyl-carbonyl.
In another preference, R
5, R
6, R
7,R
8, R
9, R
10, R
11And R
12Be H independently of one another, saturated or unsaturated C
1-8Alkyl, halogen, C
1-8Saturated or unsaturated alkoxyl group, halo C
1-8Saturated or unsaturated alkoxyl group, C
1-8Alkyl-ester group (RCOO-), C
1-8Alkyl-sulphonyl ester group or fluoroform sulfonyl ester.
In another preference, R
5, R
6, R
7, R
8, R
9, R
10, R
11And R
12Be hydrogen independently of one another, methyl, chlorine, bromine, methoxy or ethoxy; Preferred hydrogen, methyl, or methoxyl group.
In another preference, Z is nitro, cyano group, ester group, aldehyde radical, carboxyl, trifluoromethyl, trifluoroacetyl group, or trifyl.
In another preference, the preferred nitro of Z.
In a second aspect of the present invention, a kind of agricultural composition is provided, it comprises:
(a) acceptable salt or their combination on the compound described in the first aspect present invention of 0.0001-99.99 weight %, its optical isomer, cis-trans-isomer or the Pesticide Science; And
(b) acceptable carrier and/or vehicle on the Pesticide Science.
In a preference, component (a) accounts for the 0.01-99.9 weight % of described agricultural composition, preferred 0.05-90 weight %.
In another preference, described agricultural composition is used for killing or prevent to be selected from down the insect of group: Coleoptera, lepidopteran, Hemiptera, Orthoptera, Isoptera or dipteral insect.
In another preference, described insect has pierce-suck type or rasping sucking mouthparts.
In another preference, described insect is aphid, plant hopper, aleyrodid, leafhopper, thrips, bollworm, cabbage caterpillar, small cabbage moth, prodenia litura or mythimna separata.
In another preference, described agricultural composition also comprises other active substance, and described other active substance is selected from: sterilant, bait formulation, sterilant, miticide, nematocides, mycocide or growth control agent.
In a third aspect of the present invention, the purposes of the described agricultural composition of second aspect present invention is provided, be used for killing or preventing the insect of Agricultural pests, sanitary insect pest and harm animal health; Or with acting on the insecticides of killing or prevent Agricultural pests, sanitary insect pest and harm animal health.
In a fourth aspect of the present invention, a kind of method for preparing the described agricultural composition of second aspect present invention is provided, has comprised step: with acceptable salt or their combination on compound, its optical isomer, cis-trans-isomer or the Pesticide Science described in (a) first aspect present invention; Mix with acceptable carrier and/or vehicle on (b) Pesticide Science, thereby form agricultural composition.
In a fifth aspect of the present invention, a kind of desinsection and/or insect protected method are provided, and described method comprises the composition described in the compound described in the first aspect or the second aspect is put in the plant materials that suffers or may insect infestation, animal body, soil or environment around it.
In a sixth aspect of the present invention, provide the purposes of acceptable salt on compound described in the first aspect, its optical isomer, cis-trans-isomer or the Pesticide Science or their combination, for the preparation of the insecticides that is used for killing or preventing Agricultural pests, sanitary insect pest and harm animal health.
In a seventh aspect of the present invention, the preparation method of acceptable salt on the described compound of first aspect, its optical isomer, cis-trans-isomer or the Pesticide Science is provided, when X=N, comprise step:
In polar solvent, in the presence of the acid of catalytic amount, with compound W and R
4NH
2Inorganic acid salt or organic acid salt, react with formula A0 compound, formula B0 compound or formula C0 compound respectively, thereby obtain formula A1 compound respectively, formula B1 compound, or formula C1 compound;
Above-mentioned various in, R
1, R
2, R
3, R
4, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z in the first aspect present invention definition.
In another preference, the acid of described catalytic amount is one or more protonic acids or the Lewis acid that is selected from down in the group: hydrochloric acid, acetic acid, SODIUM PHOSPHATE, MONOBASIC, tosic acid, trifluoroacetic acid, boron trifluoride, aluminum chloride, iron trichloride, magnesium chloride, cobalt chloride, strontium chloride, Palladous chloride or nickelous chloride.
In another preference, described polar solvent is acetonitrile.
In another preference, described temperature of reaction is-78-50 ℃, preferably is-20-40 ℃.
In another preference, the described reaction times is 2-48 hour, preferably is 6-24 hour.
In a eighth aspect of the present invention, provide the preparation method of acceptable salt on the described compound of first aspect present invention, its optical isomer, cis-trans-isomer or the Pesticide Science, as X=S, SO or SO
2The time, comprise step:
(1) in polar solvent, with formula A ' compound, formula B ' compound or formula C ' compound and CH
3I reaction back, again and Na
2The S reaction, thus formula A2 compound, formula B2 compound or formula C2 compound obtained respectively;
Above-mentioned various in, R
1, R
2, R
3, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z in the first aspect present invention definition;
(2) in inert solvent, with formula A2 compound, formula B2 compound or formula C2 compound and benzoyl hydroperoxide (mCPBA) reaction, thus obtain formula A3 compound, formula A4 compound, formula B3 compound, formula B4 compound respectively, formula C3 compound, formula C4 compound;
Above-mentioned various in, R
1, R
2, R
3, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z in the first aspect present invention definition, X
3=SO, X
4=SO
2
In another preference, described inert solvent is methylene dichloride.
In should be understood that within the scope of the present invention, above-mentioned each technical characterictic of the present invention and can making up mutually between specifically described each technical characterictic in below (eg embodiment), thus constitute new or optimized technical scheme.As space is limited, this tired stating no longer one by one.
Embodiment
The inventor is by long-term and deep research, on the architecture basics of existing nitro-methylene-type neonicotine sterilant, kept active pharmacophore Nitromethylene, by dialdehyde, primary amine hydrochloride, methyl iodide, sodium sulphite, benzoyl hydroperoxide and the reaction of Nitromethylene compounds, synthesized a kind of novel assorted bridged ring anabasine compound, the insecticidal activity of this compound significantly improves, and has the insecticidal spectrum of expansion.On this basis, the contriver has finished the present invention.
Group definition
As used herein, term " C
1-8Alkyl " the saturated or unsaturated group of carbon containing, hydrogen only such as alkyl, thiazolinyl, alkynyl, cycloalkyl, cycloalkenyl group, aryl that refers to have 1-8 carbon atom, preferred C
1-8Alkyl, C
2-8Thiazolinyl or C
2-8Alkynyl.
Term " thiazolinyl " refers to have the thiazolinyl of the straight or branched of 2-8 carbon atom, for example vinyl, allyl group, 1-propenyl, pseudoallyl, 1-butylene base, crotyl or similar group.
Term " alkynyl " refers to have the alkynyl of the straight or branched of 2-8 carbon atom, for example ethynyl, proyl etc.
Term " saturated or unsaturated C
1-8Alkyl " comprise C
1-8Alkyl, C
2-8Thiazolinyl and C
2-8Alkynyl.
Term " cycloalkyl " finger ring propyl group, cyclobutyl, cyclopentyl, cyclohexyl or suberyl etc.
As used herein, term " C
1-8Alkyl " refer to have the straight or branched alkyl of 1-8 carbon atom, for example methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-, sec-butyl, the tertiary butyl or similar group.
Term " C
1-8Alkoxyl group " refer to have the straight or branched alkoxyl group of 1-8 carbon atom, for example methoxyl group, oxyethyl group, propoxy-, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert.-butoxy or similar group.
Term " halogen " refers to fluorine, chlorine, bromine or iodine.Term " halo " refers to by the group of identical or different one or more above-mentioned halogen atom replacement, for example trifluoromethyl, pentafluoroethyl group or similar group.
Term " five yuan or hexa-member heterocycle base " refers to contain one or more heteroatomic five yuan or six-rings that are selected from nitrogen, oxygen or sulphur, for example pyridyl, thiazolyl, pyrimidyl, tetrahydrofuran base, Huo oxazolyl etc.
Groups such as term " alkylsulfonyl " nail base alkylsulfonyl, ethylsulfonyl, trifluoromethyl sulfonyl.
Term " aromaticacyl radical " comprises groups such as benzoyl, pyridine formyl radical.
Therefore compound of the present invention can contain one or more asymmetric centers, and occurs with the form of raceme, racemic mixture, single enantiomer, diastereomeric compound and single diastereomer.The asymmetric center that can exist depends on various substituent character on the molecule.Each this asymmetric center will produce two optically active isomers independently, and all possible optically active isomer and non-enantiomer mixture and pure or partial-purified compound comprise within the scope of the present invention.The present invention includes all isomeric form of compound.
The insecticidal activity of active substance of the present invention
Term " active substance of the present invention " or " active compound of the present invention " refer to acceptable salt on The compounds of this invention, its optical isomer, cis-trans-isomer or the Pesticide Science, it has the Nitromethylene structure of pyrroles and pyrrolin condensed ring, it has significant insecticidal activity, insecticidal spectrum is wide, and stability is strong.
Term " acceptable salt on the Pesticide Science " means formula 1 compound of the present invention and suitable acid or alkali and forms the sterilant pharmacy acceptable salt.Preferably, this salt is the anion salt of the compound of formula 1.Preferably, this salt is water miscible.Typically, comprise the salt that mineral acid forms by the acid salt of formula 1 compound formation, for example hydrochloride, phosphoric acid salt, vitriol, nitrate etc.; And comprise the salt that organic acid forms, and as acetate, benzoate etc.
Actives mass-energy of the present invention is as control and eliminate agriculture and forestry plant insect, the insect of storage cereal, the insect that endangers animal health and public health insect etc. widely.In this manual, " sterilant " is the general designation with material of the effect that prevents and treats above-mentioned all insects of mentioning.
The example of insect includes but not limited to: coleopteron, as sitophilus zea-mais (Sitophilus zeamais), red flour beetle (Tribolium castaneum), potato bug (Henosepilachna vigintioctomaculata), potato ladybug (Henosepilachna sparsa), agriotes fussicollis (Agriotes fuscicollis), red pin green gold tortoise (Anomala cupripes), beautiful tortoise with four lines (Popillia quadriguttata), colorado potato beetles (Monolepta hieroglyphica), ponderous borer (Monochamus alternatus), rice root weevil (Echinocnemus squameus), paulownia chrysomelid (Basiprionota bisignata), longicorn beetle (Anoplophora chinensis), mulberry borer (Apriona germari), navel abdomen bark beetle (Scolytus schevy), or Agriotes subrittatus Motschulsky (Agriotes fuscicollis); Lepidopterous insects, as wave malicious pretty young woman (Lymantria dispar), tent caterpillar (Malacosoma neustria testacea), the wild snout moth's larva (Diaphania perspectalis) of Chinese littleleaf box thin,tough silk, Clania variegata Snellen (Clania variegata), cnidocampa flavescens walker (Cnidocampa flavscens), dendrolimus punctatus (Dendrolimus punctatus), orgyia antiqua (Orgyia gonostigma), paranthrene tabaniformis (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), greater wax moth (Galleria mellonella), diamond-back moth (Plutella xylostella), tangerine lyonetid (Phyllocnistis citrella), or oriental armyworm (Mythimna separata); Homoptera insect, as rice green leafhopper (Nephotettix cincticeps), Nilaparvata lugen (brown planthopper) (Nilaparvata lugens), Kang Shi mealybug (Pseudococcus comstocki), arrowhead scales (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, as Groton bug (Blattella germanica), the big Lian of the U.S. (Periplaneta americana), African mole cricket (Gryllotalpa africana), or Asia migratory locusts (Locus migratoria); Isoptera insect, as invasion red fire ant (Solenopsis invicta), or Coptotermes formosanus Shtrari (Coptotermes formosanus); Dipteral insect, as housefly (Musca domestica), Aedes aegypti (Aedes aegypti) is planted fly (Delia platura), culex (Culex sp.), or Anopheles sinensis (Anopheles sinensis);
The insect of harm animal health, as boophilus microplus (Boophilus microplus), haemaphysalis longicornis (Haemaphysalis longicornis), hyalomma anatolicum anatolicum (Hyalomma anatolicum), bomb fly (Hypoderma spp.), liver fluke (Fasciola hepatica), Bei Shi moniezia (Moniezia benedeni), oersted nematode (Ostertagia spp.), Trypanosoma evansi (Trypanosoma evansi, Babesia bigemina), coccidia (Coccidium) etc.
The compound that the present invention relates to especially to pierce-suck type, rasping sucking mouthparts insect as: agriculture and forestry injurious insects such as aphid, leafhopper, plant hopper, thrips, aleyrodid have special efficacy.
The insecticides that contains active substance of the present invention
Active substance of the present invention can be prepared into insecticides with the method for routine.These active compounds can be made conventional preparation, solution for example, emulsion, suspensoid, pulvis, foaming agent, paste, granule; Aerosol, natural and synthetic material with the active substance dipping, microcapsule in polymer, the dressing compound that is used for seed, with with the preparation of a use of combustion unit, sootiness cartridge case for example, sootiness jar and sootiness dish, and the cold mist of ULV (Cold mist) and hot mist (Warm mist) preparation.
These preparations can be with known method production, for example, with active compound with expand agent and mix, these expand agent is exactly the diluent or carrier of liquid or liquefied gas or solid, and can to select tensio-active agent arbitrarily for use be emulsifying agent and/or dispersion agent and/or foam formation agent.For example when using water as the expansion agent, organic solvent also can be used as auxiliary agent.
When making diluent or carrier with liquid solvent, be suitable basically, as arene, dimethylbenzene for example, toluene or alkylnaphthalene; The fragrance of chlorination or the fat hydrocarbon of chlorination, chlorobenzene for example, vinylchlorid or methylene dichloride; Fat hydrocarbon, for example hexanaphthene or paraffin, for example mineral oil fractions; Alcohols, for example ethanol or ethylene glycol and their ether and lipid; Ketone, acetone for example, methylethylketone, methyl iso-butyl ketone (MIBK) or pimelinketone; Or the polar solvent that is of little use, for example dimethyl formamide and dimethyl sulfoxide (DMSO), and water.
Diluent or carrier with regard to liquefied gas is said, refers to the liquid that will become gas at normal temperatures and pressures, and aerosol propellants for example is as hydro carbons and butane, propane, nitrogen and the carbonic acid gas of halogenation.
Solid carrier can be with the natural mineral substance that grinds, kaolin for example, clay, talcum, quartz, atlapulgite, polynite, or diatomite and grind synthetic mineral substance, for example silicic acid of high dispersing, aluminum oxide and silicate.The solid carrier of using for particle is that pulverize and natural announcement stone classification, calcite for example, marble, float stone, sepiolite and rhombspar, and the synthetic particle of inorganic and organic meal, with organic materials wood sawdust for example, Exocarpium cocois (Cocos nucifera L), the particle of corn cob and tobacco stems etc.
Emulsification row non-ionic and negatively charged ion can be used as emulsifying agent and/or foam forms agent.Polyoxyethylene-fatty acid ester for example, polyoxyethylene-Fatty Alcohol(C12-C14 and C12-C18) ethers, for example alkaryl polyoxyethylene glycol ethers, alkyl sulfonates, alkyl sulfuric ester class, aromatic yl sulphonate class and albumin hydrolysate.Dispersion agent comprises, for example xylogen sulfite waste lye and methylcellulose gum.
In preparation, can use tackiness agent, carboxymethyl cellulose and with powder for example, the natural and synthetic polymer of particle or emulsion form, gum arabic for example, the pure and mild polyvinyl acetate of polyvinyl.
Can be with tinting material inorganic dyestuff for example, as ferric oxide, oxidation is bored and is Prussian blue; Organic dye is as organic dye, as azo dyes or metal titanium cyanine dyes; With use the trace nutrition agent, violent as iron, boron, copper, cobalt, the salt of aluminum and zinc etc.
These active compounds of the present invention can be made in the commodity preparation that a kind of mixture is present in them or from the use formulation of these formulation preparation with other active compounds, these other active compound is sterilant, close bait, sterilant, miticide, nematocides, mycocide, growth control agent etc.Sterilant comprises, phosphoric acid ester for example, amino formate, cinerins, chlorinated hydrocarbons, benzoyl area kind, neires toxin and by the material of microorganisms, as Avrmectin.
In addition, these active compounds of the present invention also can be made in the commodity preparation that a kind of mixture is present in them to become from the use formulation of these formulation preparation with synergistic agent.Synergistic agent is the compound that improves the active compound effect, because active compound itself has activity, also can add synergistic agent.
These preparations contain usually and account for described insecticides 0.001-99.99 weight %, preferred 0.01-99.9 weight %, the more preferably active compound of the present invention of 0.05-90 weight %.The concentration of making the active compound the use formulation from the commodity preparation can change in wide scope.Use the concentration of the active compound in the formulation to be preferably between 0.0001 and 1% (g/v) from 0.0000001-100% (g/v).
The preparation method of The compounds of this invention
Compound can make by following method shown in the general formula 1 of the present invention, however the condition of this method, and for example the amount of reactant, solvent, alkali, compound used therefor, temperature of reaction, reaction required time etc. are not limited to following explanation.The compounds of this invention can also be chosen various synthetic methods that will describe in this manual or known in the art wantonly and combine and make easily, and such combination can be easy to carry out by those skilled in the art in the invention.
Used acid is protonic acid or Lewis acid in the reaction, comprise (but being not limited to): hydrochloric acid, acetic acid, SODIUM PHOSPHATE, MONOBASIC, tosic acid, trifluoroacetic acid, boron trifluoride, aluminum chloride, iron trichloride, magnesium chloride, cobalt chloride, strontium chloride, Palladous chloride or nickelous chloride, or its combination.
In a preference, compound shown in general formula 1 structure of the present invention can be synthetic by following method:
(1) when X=N, described method comprises the steps:
In polar solvent (as acetonitrile), in the presence of the acid of catalytic amount, under-78-50 ℃ (preferred-20-40 ℃), with compound W and R
4NH
2Hydrochloride (as R
4NH
2HCl), react for some time (as 2-48 hour, preferably being 6-24 hour) respectively with formula A0 compound, formula B0 compound or formula C0 compound, thereby obtain formula A1 compound respectively, formula B1 compound, or formula C1 compound;
Above-mentioned various in, R
1, R
2, R
3, R
4, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z as hereinbefore defined.
Described formula W compound can be suc as formula the compound shown in W1 or the formula W2;
Wherein, among the formula W1, R
1With define in the definition of Z as mentioned, n is the integer of 1-3;
Among the formula W2, R
1With in the definition of Z as mentioned define R
2And R
3Be H independently of one another, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl is perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, saturated or unsaturated C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl.
The preparation method of the compound shown in the compound shown in the described formula W1 or the described formula W2 can be preparation method conventional in the prior art.
A kind of preferably preparation method of described formula W1 compound comprises step:
(i) add an amount of acetonitrile in the diamines, drip the acetonitrile lysate of formula F compound under ice bath, TLC follows the tracks of reaction process, after reaction finishes, in reaction mixture, add a large amount of water, chloroform extraction, drying, suction filtration boils off solvent, obtains oily liquids formula E compound;
(ii) formula E compound and formula G compound are made solvent with inert solvent (as ethanol), reflux for some time (as 2-16 hour or 4-8 hour), and cooling is left standstill, and the solid that suction filtration is separated out obtains product formula W1 compound;
Above-mentioned various in, R
1Define in as mentioned with Z, n is the integer of 1-3.
A kind of preferably preparation method of described formula W2 compound comprises step:
(a) R
2NH
2Add an amount of acetonitrile in the aqueous solution, drip the acetonitrile solution of formula F compound under ice bath, TLC follows the tracks of reaction process, after reaction finishes, in reaction mixture, add a large amount of water, dichloromethane extraction, drying, suction filtration boils off solvent, obtains oily liquids formula H compound;
(b) formula H compound and formula G compound, in inert solvent (as ethanol), for some time of refluxing (as 2-16 or 4-8 hour), concentrate, column chromatography for separation obtains product formula J compound;
(c) (as 4-8 hour) in inert solvent (as ethanol), reacted for some time in formula J compound and amine reaction under ice bath, concentrate, and column chromatography for separation obtains formula W2 compound;
Above-mentioned various in, R
1With in the definition of Z as mentioned define R
2And R
3Be H independently of one another, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl is perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, saturated or unsaturated C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl.
(2) as X=S, SO or SO
2The time, comprise step:
(I) in polar solvent (as ethanol), respectively with formula A ' compound, formula B ' compound or formula C ' compound and CH
3After the I reaction (as stirring at room 2-8 hour), add a little ether, filter collecting precipitation; Precipitation and sodium sulphite reaction (as water-soluble together, under 80-100 ℃, reacting 1-4 hour) with collecting after reaction finishes, concentrate, column chromatography, thus obtain formula A2 compound, formula B2 compound or formula C2 compound respectively;
In the formula, R
1, R
2, R
3, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z as hereinbefore defined; (II) in inert solvent (as methylene dichloride), respectively with formula A2 compound, formula B2 compound, or formula C2 compound and benzoyl hydroperoxide (mCPBA) reaction, reacted 1-4 hour, and after reacting completely, concentrated, column chromatography, thus formula A3 compound, formula A4 compound, formula B3 compound, formula B4 compound, formula C3 compound or formula C4 compound obtained respectively.
In the formula, R
1, R
2, R
3, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z as hereinbefore defined.
Wherein, the amount by the control benzoyl hydroperoxide can obtain formula A3 compound, formula A4 compound, formula B3 compound, formula B4 compound, formula C3 compound or formula C4 compound respectively.
Major advantage of the present invention comprises:
(a) the invention provides the compound of a class formation novelty, the insecticidal activity of this compound significantly improves;
(b) compound provided by the invention has the insecticidal spectrum of expansion, bean sprouts and mythimna separata has all been shown the insecticidal activity of highly significant.
Below in conjunction with concrete enforcement, further set forth the present invention.Should be understood that these embodiment only to be used for explanation the present invention and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example, usually according to normal condition, or the condition of advising according to manufacturer.Unless otherwise indicated, otherwise per-cent and umber calculate by weight.
Embodiment 1-44: the preparation of assorted bridged ring anabasine compound
Embodiment 1 1-((6-chloropyridine-3-yl) methyl)-8-nitro-1,2,3,5,6,7-six hydrogen-5,7-epimino imidazo [1,2-a] pyridine (compd A-1) synthetic:
To add the 20ml acetonitrile in the ammonium chloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 0.531g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 42%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): δ 150.02,149.48,148.61,138.84,130.35,123.76,54.68,50.86,50.62,37.44ppm; HRMS (ES+) C
13H
14 35ClN
5O
2(M+H)
+, calculated value: 308.0836; Measured value: 308.0756; C
13H
14 37ClN
5O
2(M+H)
+, calculated value: 310.0807; Measured value: 310.0743.
Embodiment 2 1-((6-chloropyridine-3-yl) methyl)-9-methyl-8-nitro-1,2,3,5,6,7-six hydrogen-5,7-epimino imidazo [1,2-a] pyridine (compd A-2) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 0.671g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 34%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=1.6Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
14H
16 35ClN
5O
2(M+H)
+, calculated value: 322.0993; Measured value: 322.0778; C
14H
16 37ClN
5O
2(M+H)
+, calculated value: 324.0963; Measured value: 324.0765.
Embodiment 3 1-((6-chloropyridine-3-yl) methyl)-9-phenyl-8-nitro-1,2,3,5,6,7-six hydrogen-5,7-epimino imidazo [1,2-a] pyridine (compd A-18) synthetic:
To add the 20ml acetonitrile in the aniline hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.290g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=1.4Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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), and 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), and 2.75-2.65 (m, 1H), 2.27-2.17 (m, 1H) ppm;
13C NMR (100MHz, DMSO-d
6): 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+) C
19H
18 35ClN
5O
2(M+H)
+, calculated value: 384.1149; Measured value: 384.0974; C
19H
18 37ClN
5O
2(M+H)
+, calculated value: 386.1120; Measured value: 386.0951.
Embodiment 4 1-((6-chloropyridine-3-yl) methyl)-9-methyl-8-cyano group-1,2,3,5,6,7-six hydrogen-5,7-epimino imidazo [1,2-a] pyridine (compd A-38) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-(1-((6-chloropyridine-3-yl) methyl) tetrahydroglyoxaline-2-subunit) acetonitrile of 1.170g (5.0mmol) and 0.671g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 34%.
1H NMR δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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), 2.49 (m, 1H), 2.26 (s, 3H), 1.79 (m, 1H) ppm;
13CNMR (100MHz, DMSO-d
6): 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+) C
15H
16 35ClN
5(M+H)
+, calculated value: 302.1094; Measured value: 302.0047; C
15H
16 37ClN
5(M+H)
+, calculated value: 304.1065; Measured value: 304.0018.
Embodiment 5 N-((2-diuril azoles-5-yl) methyl)-N-ethyl-2,6-dimethyl-4-nitro-2,6-diazabicylo [3.1.1] heptan-3-alkene-3-amine (compd A-50) synthetic:
With N-((2-diuril azoles-5-yl) methyl)-N-ethyl-N-methyl-2-nitroethylene-1 of 1.380g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.671g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 36%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): δ 159.18,155.82,142.12,140.55,48.03,45.58,41.67,39.81,31.94,13.15ppm; HRMS (ES+) C
13H
18 35ClN
5O
2S (M+H)
+, calculated value: 344.0870; Measured value: 344.0687; C
13H
18 37ClN
5O
2S (M+H)
+, calculated value: 346.0840; Measured value: 346.0657.
Embodiment 6 1-((6-chloropyridine-3-yl) methyl)-8-nitro-N-phenyl-1,2,3,5,6,7-six hydrogen-5,7-epimino imidazo [1,2-a] pyridine-9-amine (compd A-23) synthetic:
To add the 20ml acetonitrile in the phenylhydrazine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.440g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, filter and obtain the pure product of pale yellow powder shape, productive rate is 47%.
1H NMR (400MHz, DMSO-d
6) δ 8.70 (d, J=2.9Hz, 1H), 8.04 (dd, J
1=8.0Hz, J
2=2.0Hz, 1H), 7.38-7.17 (m, 3H), 7.13-7.00 (m, 2H), and 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-d
6): 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+) C
19H
19 35ClN
6O
2(M+H)
+, calculated value: 399.1258; Measured value: 399.0987; C
19H
19 37ClN
6O
2(M+H)
+, calculated value: 401.1229; Measured value: 401.0973.
Embodiment 7 1-((6-chloropyridine-3-yl) methyl)-N-sec.-propyl-8-nitro-N-phenyl-1,2,3,5,6,7-six hydrogen-5,7-epimino imidazo [1,2-a] pyridine-9-amine (compd A-28) synthetic:
To add the 20ml acetonitrile in 1-sec.-propyl-1-hydrazinobenzene hydrochloride salt of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.881g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
22H
25 35ClN
6O
2(M+H)
+, calculated value: 441.1728; Measured value: 441.1587; C
22H
25 37ClN
6O
2(M+H)
+, calculated value: 443.1698; Measured value: 443.1568.
Embodiment 8 1-((6-chloropyridine-3-yl) methyl)-8-nitro-1,2,3,5,6,7-six hydrogen-5,7-epithio imidazo [1,2-a] pyridine (compd A-33) synthetic:
With 1-((6-chloropyridine-3-yl) methyl)-9-methyl-8-nitro-1,2,3,5,6 of 1.605g (5.0mmol), 7-six hydrogen-5 add the 20ml acetonitrile in 7-epimino imidazo [1, the 2-a] pyridine, slowly drip the methyl iodide of 0.852g (6.0mmol).React after 2 hours, filter and obtain brown solid, productive rate is 91%.Na with this brown solid 2.084g (4.5mmol) and 0.421g (5.4mmol)
2S is soluble in water, under the nitrogen protection, and after reacting 2 hours under 85 ℃, desolventizing, it is 40% that column chromatography for separation obtains the pure product productive rate of pale yellow powder shape.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), 4.84 (s, 2H), 3.74 (m, 2H), 3.26-2.97 (m, 3H), 2.93-2.80 (m, 1H), 2.53 (m, 1H), 2.06 (m, 1H) ppm;
13C NMR (100MHz, DMSO-d
6): δ 152.47,149.48,148.61,138.84,130.35,123.76,54.68,50.62,50.46,39.12ppm; HRMS (ES+) C
13H
13 35ClN
4O
2S (M+H)
+, calculated value: 325.0448; Measured value: 325.0285; C
13H
13 37ClN
4O
2S (M+H)
+, calculated value: 327.0418; Measured value: 327.0264.
Embodiment 9 N-ethyls-2,6-dimethyl-4-nitro-N-((tetrahydrofuran (THF)-3-yl) methyl)-2,6-the synthetic of diaza-bicyclo [3.1.1] heptan-3-alkene-3-amine (compd A-64) of mixing:
With N-ethyl-N-methyl-2-nitro-N-((tetrahydrofuran (THF)-3-yl) methyl) ethene-1 of 1.145g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.671g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) 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), 2.05-1.74 (m, 2H), 1.61 (m, 1H), 1.17 (t, J=12.6Hz, 3H) ppm;
13C NMR (100MHz, DMSO-d
6): 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+) C
14H
24N
4O
3(M+H)
+, calculated value: 297.1848; Measured value: 297.1686.
Embodiment 10 1-((6-chloropyridine-3-yl) methyl)-8-nitro-1,2,3,5,6,7-six hydrogen-5,7-epithio imidazo [1,2-a] pyridine-9,9-double oxide (compd A-35) synthetic:
With 1-((6-chloropyridine-3-yl) methyl)-8-nitro-1,2,3,5,6 of 1.605g (5.0mmol), 7-six hydrogen-5 add the 20ml methylene dichloride in 7-epithio imidazo [1, the 2-a] pyridine, slowly drip the metachloroperbenzoic acid of 1.726g (10.0mmol).React after 2 hours, desolventizing, it is 60% that column chromatography for separation obtains the pure product productive rate of pale yellow powder shape.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): δ 162.29,149.48,148.61,138.84,130.35,123.76,54.68,50.62,50.46,32.02ppm; HRMS (ES+) C
13H
13 35ClN
4O
4S (M+H)
+, calculated value: 356.0346; Measured value: 356.0296; C
13H
13 37ClN
4O
4S (M+H)
+, calculated value: 358.0317; Measured value: 358.0272.
Embodiment 11 1-((6-chloropyridine-3-yl) methyl)-9-nitro-2,3,5,6,7,8-six hydrogen-1H-5,8-epimino imidazo [1,2-a] azepine (compd B-1) synthetic:
To add the 20ml acetonitrile in the ammonium chloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 0.531g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 38%.
1H NMR (400MHz, DMSO-d
6) δ 8.66 (d, J=2.9Hz, 1H), 8.01 (dd, J
1=8.0Hz, J
2=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), and 1.72-1.41 (m, 2H), 1.32-1.11 (m, 1H) ppm;
13C NMR (100MHz, DMSO-d
6): 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+) C
14H
16 35ClN
5O
2(M+H)
+, calculated value: 322.0993; Measured value: 322.0763; C
14H
16 37ClN
5O
2(M+H)
+, calculated value: 323.0963; Measured value: 323.0748.
Embodiment 12 1-((6-chloropyridine-3-yl) methyl)-10-methyl-9-nitro-2,3,5,6,7,8-six hydrogen-1H-5,8-epimino imidazo [1,2-a] azepine (compd B-2) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 0.671g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
15H
18 35ClN
5O
2(M+H)
+, calculated value: 336.1149; Measured value: 336.0986; C
15H
18 37ClN
5O
2(M+H)
+, calculated value: 338.1120; Measured value: 338.0957.
Embodiment 13 1-((6-chloropyridine-3-yl) methyl)-9-nitro-10-phenyl-2,3,5,6,7,8-six hydrogen-1H-5,8-epimino imidazo [1,2-a] azepine (compd B-18) synthetic:
To add the 20ml acetonitrile in the aniline hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.290g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of yellow powder shape, and productive rate is 33%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=2.0Hz, 1H), 7.34 (d, J=14.9Hz, 1H), and 7.30-7.13 (m, 2H), 7.01-6.86 (m, 2H), and 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-d
6): 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+) C
20H
20 35ClN
5O
2(M+H)
+, calculated value: 398.1306; Measured value: 398.1278; C
20H
20 37ClN
5O
2(M+H)
+, calculated value: 400.1276; Measured value: 400.1254.
Embodiment 14 1-((6-chloropyridine-3-yl) methyl)-10-methyl-9-cyano group-2,3,5,6,7,8-six hydrogen-1H-5,8-epimino imidazo [1,2-a] azepine (compd B-49) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-(1-((6-chloropyridine-3-yl) methyl) tetrahydroglyoxaline-2-subunit) acetonitrile of 1.170g (5.0mmol) and 0.671g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=1.4Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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), and 1.60-1.42 (m, 1H), 1.37-1.21 (m, 1H) ppm;
13C NMR (100MHz, DMSO-d
6): 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+) C
16H
18 35ClN
5(M+H)
+, calculated value: 316.1251; Measured value: 316.1087; C
16H
18 37ClN
5(M+H)
+, calculated value: 318.1221; Measured value: 318.1057.
Embodiment 15 N-((2-diuril azoles-5-yl) methyl)-N-ethyl-2,8-dimethyl-4-nitro-2,8-diazabicylo [3.2.1] suffering-3-alkene-3-amine (compd B-62) synthetic:
With N-((2-diuril azoles-5-yl) methyl)-N-ethyl-N-methyl-2-nitroethylene-1 of 1.380g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.671g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): 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+) C
14H
20 35ClN
5O
2S (M+H)
+, calculated value: 358.1026; Measured value: 358.0846; C
14H
20 37ClN
5O
2S (M+H)
+, calculated value: 360.0997; Measured value: 360.0817.
Embodiment 16 1-((6-chloropyridine-3-yl) methyl)-9-nitro-N-phenyl-2,3,5,6,7,8-six hydrogen-1H-5,8-epimino imidazo [1,2-a] azepine-10-amine (compd B-23) synthetic:
To add the 20ml acetonitrile in the phenylhydrazine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.440g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, filter and obtain the pure product of pale yellow powder shape, productive rate is 47%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
20H
21 35ClN
6O
2(M+H)
+, calculated value: 413.1415; Measured value: 413.1296; C
20H
21 37ClN
6O
2(M+H)
+, calculated value: 415.1385; Measured value: 415.1273.
Embodiment 17 1-((6-chloropyridine-3-yl) methyl)-N-sec.-propyl-9-nitro-N-phenyl-2,3,5,6,7,8-six hydrogen-1H-5,8-epimino imidazo [1,2-a] azepine-10-amine (compd B-28) synthetic:
To add the 20ml acetonitrile in 1-sec.-propyl-1-hydrazinobenzene hydrochloride salt of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.861g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
23H
27 35ClN
6O
2(M+H)
+, calculated value: 455.1884; Measured value: 455.0425; C
23H
27 37ClN
6O
2(M+H)
+, calculated value: 457.1855; Measured value: 457.0402.
Embodiment 18 1-((6-chloropyridine-3-yl) methyl)-9-nitro-2,3,5,6,7,8-six hydrogen-1H-5,8-epithio imidazo [1,2-a] azepine (compd B-33) synthetic:
With 1-((6-chloropyridine-3-yl) methyl)-10-methyl-9-nitro-2,3 of 1.676g (5.0mmol), 5,6,7,8-, six hydrogen-1H-5, add the 20ml acetonitrile in 8-epimino imidazo [1, the 2-a] azepine, slowly drip the methyl iodide of 0.852g (6.0mmol).React after 2 hours, filter and obtain brown solid, productive rate is 89%.Na with this brown solid 2.147g (4.5mmol) and 0.421g (5.4mmol)
2S is soluble in water, under the nitrogen protection, and after reacting 2 hours under 85 ℃, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 38%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
14H
15 35ClN
4O
2S (M+H)
+, calculated value: 339.0604; Measured value: 339.0014; C
14H
15 37ClN
4O
2S (M+H)
+, calculated value: 341.0575; Measured value: 340.9989.
Embodiment 19N-ethyl-2,8-dimethyl-4-nitro-N-((tetrahydrofuran (THF)-3-yl) methyl)-2,8-are mixed synthesizing of diaza-bicyclo [3.2.1] suffering-3-alkene-3-amine (compd B-74):
With N-ethyl-N-methyl-2-nitro-N-((tetrahydrofuran (THF)-3-yl) methyl) ethene-1 of 1.145g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.671g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) δ 3.84-3.34 (m, 8H), 3.20 (q, J=12.6Hz, 1H), 3.06-2.91 (m, 4H), 2.28-1.85 (m, 5H), 1.85-1.30 (m, 5H), 1.17 (t, J=12.6Hz, 3H) ppm;
13C NMR (100MHz, DMSO-d
6): 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+) C
15H
26N
4O
3(M+H)
+, calculated value: 311.2005; Measured value: 311.1967.
Embodiment 20 1-((6-chloropyridine-3-yl) methyl)-9-nitro-2,3,5,6,7,8-six hydrogen-1H-5,8-epithio imidazo [1,2-a] azepine-10,10-double oxide (compd B-35) synthetic:
With 1-((6-chloropyridine-3-yl) methyl)-8-nitro-1,2,3,5,6 of 1.690g (5.0mmol), 7-six hydrogen-5 add the 20ml methylene dichloride in 7-epithio imidazo [1, the 2-a] pyridine, slowly drip the metachloroperbenzoic acid of 1.726g (10.0mmol).React after 2 hours, desolventizing, it is 50% that column chromatography for separation obtains the pure product productive rate of pale yellow powder shape.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=1.4Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): δ 149.48,148.61,138.84,130.35,123.76,54.68,50.62,49.91,30.05,25.64ppm; HRMS (ES+) C
14H
15 35ClN
4O
4S (M+H)
+, calculated value: 371.0503; Measured value: 371.0147; C
14H
15 37ClN
4O
4S (M+H)
+, calculated value: 373.0473; Measured value: 373.0103.
Embodiment 21 1-((6-chloropyridine-3-yl) methyl)-10-nitro-1,2,3,5,6,7,8,9-octahydro-5,9-epimino imidazo [1,2-a] nitrogen heterocyclic suffering rare (Compound C-1) synthetic:
To add the 20ml acetonitrile in the ammonium chloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 0.531g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 38%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
15H
18 35ClN
5O
2(M+H)
+, calculated value: 336.1149; Measured value: 336.0728; C
15H
18 37ClN
5O
2(M+H)
+, calculated value: 338.1120; Measured value: 338.0688.
Embodiment 22 1-((6-chloropyridine-3-yl) methyl)-11-methyl isophthalic acid 0-nitro-1,2,3,5,6,7,8,9-octahydro-5,9-epimino imidazo [1,2-a] nitrogen heterocyclic suffering rare (Compound C-2) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 0.671g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 36%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
16H
20 35ClN
5O
2(M+H)
+, calculated value: 350.1306; Measured value: 350.1078; C
16H
20 37ClN
5O
2(M+H)
+, calculated value: 352.1276; Measured value: 352.1057.
Embodiment 23 1-((6-chloropyridine-3-yl) methyl)-10-nitro-11-phenyl-1,2,3,5,6,7,8,9-octahydro-5,9-epimino imidazo [1,2-a] nitrogen heterocyclic suffering rare (Compound C-18) synthetic:
To add the 20ml acetonitrile in the aniline hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.290g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of yellow powder shape, and productive rate is 35%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 5H), 8.05 (dd, J
1=8.0Hz, J
2=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), and 1.97-1.55 (m, 24H), 1.53 (d, J=1.8Hz, 1H), 1.50-1.31 (m, 5H) ppm;
13CNMR (100MHz, DMSO-d
6): 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+) C
21H
22 35ClN
5O
2(M+H)
+, calculated value: 412.1462; Measured value: 412.0138; C
21H
22 37ClN
5O
2(M+H)
+, calculated value: 414.1433; Measured value: 414.0114.
Embodiment 24 1-((6-chloropyridine-3-yl) methyl)-11-methyl isophthalic acid 0-cyano group-1,2,3,5,6,7,8,9-octahydro-5,9-epimino imidazo [1,2-a] nitrogen heterocyclic suffering rare (Compound C-49) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-(1-((6-chloropyridine-3-yl) methyl) tetrahydroglyoxaline-2-subunit) acetonitrile of 1.170g (5.0mmol) and 0.671g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 36%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
17H
20 35ClN
5(M+H)
+, calculated value: 330.1407; Measured value: 330.1186; C
17H
20 37ClN
5(M+H)
+, calculated value: 332.1378; Measured value: 332.1157.
Embodiment 25 N-((2-diuril azoles-5-yl) methyl)-N-ethyl-2,9-dimethyl-4-nitro-2,9-diazabicylo [3.3.1] ninth of the ten Heavenly Stems-3-alkene-3-amine (Compound C-62) synthetic:
With N-((2-diuril azoles-5-yl) methyl)-N-ethyl-N-methyl-2-nitroethylene-1 of 1.380g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.671g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 33%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): 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+) C
15H
22 35ClN
5O
2S (M+H)
+, calculated value: 372.1183; Measured value: 372.0973; C
15H
22 37ClN
5O
2S (M+H)
+, calculated value: 374.1153; Measured value: 374.0943.
Embodiment 26 1-((6-chloropyridine-3-yl) methyl)-10-nitro-N-phenyl-1,2,3,5,6,7,8,9-octahydro-5,9-epimino imidazo [1,2-a] nitrogen heterocyclic suffering is rare-11-amine (Compound C-23) synthetic:
To add the 20ml acetonitrile in the phenylhydrazine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.440g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, filter and obtain the pure product of pale yellow powder shape, productive rate is 47%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
21H
23 35ClN
6O
2(M+H)
+, calculated value: 427.1571; Measured value: 427.1256; C
21H
23 37ClN
6O
2(M+H)
+, calculated value: 429.1542; Measured value: 429.1232.
Embodiment 27 1-((6-chloropyridine-3-yl) methyl)-N-sec.-propyl-10-nitro-N-phenyl-1,2,3,5,6,7,8,9-octahydro-5,9-epimino imidazo [1,2-a] nitrogen heterocyclic suffering is rare-11-amine (Compound C-28) synthetic:
To add the 20ml acetonitrile in 1-sec.-propyl-1-hydrazinobenzene hydrochloride salt of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) pyridine of 1.270g (5.0mmol) and 1.861g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 38%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=3.1Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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), 2.60-2.48 (m, 1H), 1.92-1.48 (m, 5H), 1.46-1.26 (m, 1H), 1.22 (d, J=12.1Hz, 6H) ppm;
13C NMR (100MHz, DMSO-d
6): 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+) C
24H
29 35ClN
6O
2(M+H)
+, calculated value: 469.2041; Measured value: 469.1985; C
24H
29 37ClN
6O
2(M+H)
+, calculated value: 471.2011; Measured value: 471.1962.
Embodiment 28 1-((6-chloropyridine-3-yl) methyl)-10-nitro-1,2,3,5,6,7,8,9-octahydro-5,9-epithio imidazo [1,2-a] nitrogen heterocyclic suffering rare (Compound C-33) synthetic:
With 1-((6-chloropyridine-3-yl) methyl)-11-methyl isophthalic acid 0-nitro-1,2 of 1.745g (5.0mmol), 3,5,6,7,8,9-octahydro-5, add the 20ml acetonitrile during 9-epimino imidazo [1,2-a] nitrogen heterocyclic is hot rare, slowly drip the methyl iodide of 0.852g (6.0mmol).React after 2 hours, filter and obtain brown solid, productive rate is 88%.Na with this brown solid 2.210g (4.5mmol) and 0.421g (5.4mmol)
2S is soluble in water, under the nitrogen protection, and after reacting 2 hours under 85 ℃, desolventizing, it is 38% that column chromatography for separation obtains the pure product productive rate of pale yellow powder shape.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
15H
17 35ClN
4O
2S (M+H)
+, calculated value: 353.0761; Measured value: 353.0471; C
15H
17 37ClN
4O
2S (M+H)
+, calculated value: 355.0731; Measured value: 355.0448.
Embodiment 29 N-ethyls-2,9-dimethyl-4-nitro-N-((tetrahydrofuran (THF)-3-yl) methyl)-2,9-the synthetic of diaza-bicyclo [3.3.1] ninth of the ten Heavenly Stems-3-alkene-3-amine (Compound C-74) of mixing:
With N-ethyl-N-methyl-2-nitro-N-((tetrahydrofuran (THF)-3-yl) methyl) ethene-1 of 1.145g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.67lg (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 34%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): 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+) C
16H
28N
4O
3(M+H)
+, calculated value: 325.2161; Measured value: 325.1874.
Embodiment 30 1-((6-chloropyridine-3-yl) methyl)-10-nitro-1,2,3,5,6,7,8,9-octahydro-5,9-epithio imidazo [1,2-a] nitrogen heterocyclic suffering is rare-11,11-double oxide (Compound C-35) synthetic:
With 1-((6-chloropyridine-3-yl) methyl)-10-nitro-1,2 of 1.760g (5.0mmol), 3,5,6,7,8,9-octahydro-5, add the 20ml methylene dichloride during 9-epithio imidazo [1,2-a] nitrogen heterocyclic is hot rare, slowly drip the metachloroperbenzoic acid of 1.726g (10.0mmol).React after 2 hours, desolventizing, it is 50% that column chromatography for separation obtains the pure product productive rate of pale yellow powder shape.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
15H
17 35ClN
4O
4S (M+H)
+, calculated value: 385.0659; Measured value: 385.0468; C
15H
17 37ClN
4O
4S (M+H)
+, calculated value: 387.0630; Measured value: 387.0424.
Embodiment 31 N-((6-chloropyridine-3-yl) methyl)-N-ethyl-2,6-dimethyl-4-nitro-2,6-diazabicylo [3.1.1] heptan-3-alkene-3-amine (compd A-33) synthetic:
With N-((6-chloropyridine-3-yl) methyl)-N-ethyl-N-methyl-2-nitroethylene-1 of 1.350g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.671g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 36%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): 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+) C
15H
20 35ClN
5O
2(M+H)
+, calculated value: 338.1306; Measured value: 338.1126; C
15H
20 37ClN
5O
2(M+H)
+, calculated value: 340.1276; Measured value: 340.1102.
Embodiment 32 N-((6-chloropyridine-3-yl) methyl)-N-ethyl-2,8-dimethyl-4-nitro-2,8-diazabicylo [3.2.1] suffering-3-alkene-3-amine (compd B-44) synthetic:
With N-((6-chloropyridine-3-yl) methyl)-N-ethyl-N-methyl-2-nitroethylene-1 of 1.350g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.671g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=3.1Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
16H
22 35ClN
5O
2(M+H)
+, calculated value: 352.1462; Measured value: 352.1233; C
16H
22 37ClN
5O
2(M+H)
+, calculated value: 354.1433; Measured value: 354.1212.
Embodiment 33 N-((6-chloropyridine-3-yl) methyl)-N-ethyl-2,9-dimethyl-4-nitro-2,9-diazabicylo [3.3.1] ninth of the ten Heavenly Stems-3-alkene-3-amine (Compound C-44) synthetic:
With N-((6-chloropyridine-3-yl) methyl)-N-ethyl-N-methyl-2-nitroethylene-1 of 1.350g (5.0mmol), add the 20ml acetonitrile in the methylamine hydrochloride of 1-diamines and 0.671g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 33%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
17H
24 35ClN
5O
2(M+H)
+, calculated value: 366.1619; Measured value: 366.1486; C
17H
24 37ClN
5O
2(M+H)
+, calculated value: 368.1589; Measured value: 368.1462.
Embodiment 34 9-methyl-8-nitro-1-((tetrahydrofuran (THF)-3-yl) methyl)-1,2,3,5,6,7-six hydrogen-5,7-epimino imidazo [1,2-a] pyridine (compd A-71) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-(Nitromethylene)-1-((tetrahydrofuran (THF)-3-yl) methyl) tetrahydroglyoxaline of 1.065g (5.0mmol) and 0.671g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): δ 152.31,71.54,68.13,53.05,51.69,49.95,41.67,39.85,31.15,30.04ppm; HRMS (ES+) C
13H
20N
4O
3(M+H)
+, calculated value: 280.1535; Measured value: 280.1273.
Embodiment 35 10-methyl-9-nitro-1-((tetrahydrofuran (THF)-3-yl) methyl)-2,3,5,6,7,8-six hydrogen-1H-5,8-epimino imidazo [1,2-a] azepine (compd B-80) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-(Nitromethylene)-1-((tetrahydrofuran (THF)-3-yl) methyl) tetrahydroglyoxaline of 1.065g (5.0mmol) and 0.671g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 37%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): 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+) C
14H
22N
4O
3(M+H)
+, calculated value: 295.1692; Measured value: 295.1473.
Embodiment 36 11-methyl isophthalic acid 0-nitro-1-((tetrahydrofuran (THF)-3-yl) methyl)-1,2,3,5,6,7,8,9-octahydro-5,9-epimino imidazo [1,2-a] nitrogen heterocyclic octene (Compound C-80) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-(Nitromethylene)-1-((tetrahydrofuran (THF)-3-yl) methyl) tetrahydroglyoxaline of 1.065g (5.0mmol) and 0.671g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 34%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): 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+) C
15H
24N
4O
3(M+H)
+, calculated value: 309.1848; Measured value: 309.0128.
Embodiment 37 2-chloro-5-(synthesizing of (9-methyl-8-nitro-2,3,6,7-tetrahydrochysene-5,7-epimino imidazo [1,2-a] pyridine-1 (5H)-yl) methyl) thiazole (compd A-57):
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) thiazole of 1.300g (5.0mmol) and 0.671g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 35%.
1H NMR (400MHz, DMSO-d
6) 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), 2.91 (t, J=13.7Hz, 1H), 2.45 (m, 1H), 2.26 (s, 3H), 1.82 (m, 1H) ppm;
13C NMR (100MHz, DMSO-d
6): δ 159.18,152.72,142.12,140.55,51.50,49.95,47.97,41.67,31.15ppm; HRMS (ES+) C
12H
14 35ClN
5O
2S (M+H)
+, calculated value: 328.0557; Measured value: 328.0287; C
12H
14 37ClN
5O
2S (M+H)
+, calculated value: 330.0527; Measured value: 330.0257.
Synthesizing of embodiment 38 2-chloro-5-((10-methyl-9-nitro-2,3,5,6,7,8-six hydrogen-1H-5,8-epimino imidazo [1,2-a] azepine-1-yl) methyl) thiazole (compd B-68):
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) thiazole of 1.300g (5.0mmol) and 0.671g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 39%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): δ 159.18,142.12,140.55,55.70,51.50,48.79,47.97,38.45,27.89,24.75ppm; HRMS (ES+) C
13H
16 35ClN
5O
2S (M+H)
+, calculated value: 342.0713; Measured value: 342.0568; C
13H
16 35ClN
5O
2S (M+H)
+, calculated value: 344.0684; Measured value: 344.0549.
Embodiment 39 2-chloro-5-(synthesizing of (11-methyl isophthalic acid 0-nitro-2,3,6,7,8,9-six hydrogen-5,9-epimino imidazo [1,2-a] nitrogen heterocyclic octene-1 (5H)-yl) methyl) thiazole (Compound C-68):
To add the 20ml acetonitrile in the methylamine hydrochloride of 2-chloro-5-((2-(Nitromethylene) tetrahydroglyoxaline-1-yl) methyl) thiazole of 1.300g (5.0mmol) and 0.671g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 34%.
1H NMR (400MHz, DMSO-d
6) 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-d
6): 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+) C
14H
18 35ClN
5O
2S (M+H)
+, calculated value: 356.0870; Measured value: 356.0687; C
14H
18 37ClN
5O
2S (M+H)
+, calculated value: 358.0840; Measured value: 358.0657.
Embodiment 40 1-((6-chloropyridine-3-yl) methyl)-10-methyl-9-nitro-2,3,4,6,7,8-six hydrogen-1H-6,8-epimino pyrido [1,2-a] pyrimidine (compd A-44) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 1-((6-chloropyridine-3-yl) methyl)-2-(Nitromethylene) hexahydropyrimidine of 1.340g (5.0mmol) and 0.671g (10.0mmol), slowly drip the mda of 0.360g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 36%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
15H
18 35ClN
5O
2(M+H)
+, calculated value: 336.1149; Measured value: 336.0856; C
15H
18 37ClN
5O
2(M+H)
+, calculated value: 338.1120; Measured value: 338.0832.
Embodiment 41 1-((6-chloropyridine-3-yl) methyl)-11-methyl isophthalic acid 0-nitro-1,2,3,4,6,7,8,9-octahydro-6,9-epimino Mi Dingbing [1,2-a] azepine (compd B-56) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 1-((6-chloropyridine-3-yl) methyl)-2-(Nitromethylene) hexahydropyrimidine of 1.340g (5.0mmol) and 0.671g (10.0mmol), slowly drip the suceinic aldehyde of 0.430g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 39%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
16H
20 35ClN
5O
2(M+H)
+, calculated value: 350.1306; Measured value: 350.1046; C
16H
20 37ClN
5O
2(M+H)
+, calculated value: 352.1276; Measured value: 352.1022.
Embodiment 42 1-((6-chloropyridine-3-yl) methyl)-12-methyl isophthalic acid 1-nitro-2,3,4,6,7,8,9,10-octahydro-1H-6,10-epimino Mi Dingbing [1,2-a] nitrogen heterocyclic suffering rare (Compound C-56) synthetic:
To add the 20ml acetonitrile in the methylamine hydrochloride of 1-((6-chloropyridine-3-yl) methyl)-2-(Nitromethylene) hexahydropyrimidine of 1.340g (5.0mmol) and 0.671g (10.0mmol), slowly drip the glutaraldehyde of 0.501g (5.0mmol).React after 24 hours, desolventizing, column chromatography for separation obtains the pure product of pale yellow powder shape, and productive rate is 38%.
1H NMR (400MHz, DMSO-d
6) δ 8.71 (d, J=2.9Hz, 1H), 8.05 (dd, J
1=8.0Hz, J
2=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-d
6): 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+) C
17H
22 35ClN
5O
2(M+H)
+, calculated value: 364.1462; Measured value: 364.1203; C
17H
22 37ClN
5O
2(M+H)
+, calculated value: 366.1433; Measured value: 366.1179.
The preparation of other compounds in embodiment 43 tables 1～3
Repeat the method among the embodiment 1-42, difference is corresponding starting raw material in employing table 1～3, thereby makes 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, has piercing mouth parts, is a kind of common crop pests.(Aphis craccivora) is tested object with bean aphid, adopts the pickling process test.
Operating process: the accurate various samples of weighing, add N respectively, dinethylformamide is mixed with the 10g/L mother liquor, with the aqueous solution that contains 0.2mL/L Triton X-100 it is diluted to the concentration of 500ug/mL during experiment.Treat aptery one-tenth aphid the bean sprouts is stable suck after, immerse in the soup that concentration is 500ug/mL together with the bean sprouts, take out behind the 5s, inhale with thieving paper and remove unnecessary soup, move in the clean vessel and raise in 23 ℃ of constant temperature.Every concentration is established 3 repetitions, and control group is the aqueous solution that contains 0.2mL/L Triton X-100.Handle after 24 hours, the dead borer population of statistics examination aphid, and calculate mortality ratio (%), the results are shown in Table 1～table 3.
Mortality ratio (%)=(contrast borer population alive-processing borer population alive)/contrast borer population alive * 100%
(2): to the insecticidal activity of mythimna separata
The leaf feeding method is soaked in employing.Fresh maize leaf was flooded 3 seconds in above-mentioned solution, and airing is at room temperature got food for the examination worm then, checks and calculate the mortality ratio (%) (formula is the same) of examination worm behind the 24h, and 10 examination worms are used in every processing, establish 3 repetitions.Make blank with the clear water processing, and calculate mortality ratio (%).The results are shown in Table 1～table 3.
General formula A Formula B general formula c
Table 1 has the active tabulation of representation compound of general formula A structure
Table 2 has the active tabulation of representation compound of Formula B structure
Table 3 has the active tabulation of representation compound of general formula C-structure
Embodiment 45. contains the preparation of the insecticides of The compounds of this invention
(a) oily suspension
Prepare following component in proportion: any compound among 25% (weight percent, down together) compd A-1～A-87, B-1～B-95, the C-1～C-95; 5% polyoxyethylene sorbitol, six oleic acid esters; 70% senior aliphatics hydrocarbon ils.Each component is ground in sand mill together, up to solid particulate be down to about below 5 microns till.The thickness suspension of gained can directly use, but also can use after the emulsification in water.
(b) aqeous suspension
Prepare following component in proportion: any compound among 25% compd A-1～A-87, B-1～B-95, the C-1～C-95; 3% hydration attapulgite (hydrate attapulgit); 10% calcium lignin sulphonate; 0.5% SODIUM PHOSPHATE, MONOBASIC; 61.5% water.Each component is ground in ball mill together, up to solid particulate be down to about below 10 microns till.This aqeous suspension can directly use.
(c) bait formulation
Prepare following component in proportion: any compound among 0.1-10% compd A-1～A-87, B-1～B-95, the C-1～C-95; 80% whole meal flour; The 19.9-10% molasses.These components are mixed fully, form the bait shape on demand.The edible bait can be distributed to the place that sanitary insect pest infects, and for example household or industrial site are regional such as kitchen, hospital or shop or open air, to come pest control by oral absorption.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (16)
1. compound with structure shown in the general formula 1, or acceptable salt on the optical isomer of described compound, cis-trans-isomer or the Pesticide Science:
General formula 1
In the formula:
R
1Be five yuan or hexa-member heterocycle base of nitrogenous, oxygen and/or sulphur, nitrogenous, the oxygen of halo and/or five yuan or hexa-member heterocycle base of sulphur perhaps replace or unsubstituted phenyl, and wherein, described substituting group is to be selected from down one or more in organizing: halogen, C
1-4Haloalkyl or C
1-4Halogenated alkoxy;
R
2And R
3Be H independently of one another, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl is perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, saturated or unsaturated C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps
R
2And R
3Common formation-CH
2-CH
2-,-CH
2-CH
2-CH
2-or-CH
2-MRc-CH
2-, M is the heteroatoms that is selected from down group: N in the formula, O or S, and Rc is the substituting group on the heteroatoms, is selected from H, saturated or unsaturated C
1-8Alkyl or alkoxyl group, allyl group, benzyl, phenyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl is perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl;
X is N, S, SO or SO independently
2
Wherein, when X=N, R
4Be H independently, saturated or unsaturated C
1-8Alkyl, C
1-8Haloalkyl, alkylsulfonyl, allyl group, benzyl, saturated or unsaturated C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl; Perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps be selected from a kind of in phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furans, thiophene, oxazole, quinoline, nitrogenous (oxygen, the sulphur) heteroaromatic of benzo (mixing) ring, wherein said fragrance (mixing) ring is unsubstituted or is selected from down the substituting group of organizing and replaces: halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, dimethylin, saturated or unsaturated C
1-4Alkyl, C
1-4Alkoxyl group, C
1-4Haloalkyl, or C
1-4Alkyl-carbonyl;
Perhaps when X=N, R
4Also can be independently-YR
aR
bStructure, wherein Y is N, S, SO or SO independently
2
R
aAnd R
bBe H independently of one another, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl; Perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps be selected from phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furans, a kind of in the thiophene ， oxazole, quinoline fragrance (mixing) ring, or above-mentioned fragrance (mix) encircles optionally by halogen itrile group, nitro, hydroxyl, carboxyl, saturated or unsaturated C
1-4Alkyl, C
1-4Alkoxyl group, C
1-4Alkyl-carbonyl, methylamino, or C
1-4Haloalkyl replaces;
Perhaps R
aAnd R
bCommon formation-CH
2-CH
2-,-CH
2-CH
2-CH
2-or-CH
2-MRc-CH
2-, M is the heteroatoms that is selected from down group in the formula: N, O or S; Rc is the substituting group on the heteroatoms, is selected from H, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, phenyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl is perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps
Work as X=S, SO, or SO
2The time, R
4Do not exist;
M is 1～3 integer, and works as m=1,2, or 3 o'clock, be respectively compound shown in general formula A, B, the C;
m＝1 m＝2 m＝3
General formula A Formula B general formula C
Above-mentioned various in, R
5, R
6, R
7, R
8, R
9, R
10, R
11And R
12Be H independently of one another, halogen, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, saturated or unsaturated C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxy carbonyl, carbobenzoxy, C
2-6The alkynyl carbonyl, C
2-3Alkenyl carbonyl, C
3-6Naphthene base carbonyl, aromaticacyl radical; Perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The aromaticacyl radical that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; C
1-8Saturated or unsaturated alkoxyl group, halo C
1-8Saturated or unsaturated alkoxyl group, C
1-8Alkyl-ester group (RCOO-), C
1-8Alkyl-sulphonyl ester group or fluoroform sulfonyl ester; Perhaps be phenyl ring, pyridine, naphthalene nucleus, furans or the quinoline that does not replace or replace, described substituting group is selected from down group: halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, dimethylin, saturated or unsaturated C
1-8Alkyl, C
1-8Alkoxyl group, C
1-8Haloalkyl, C
1-8Alkyl-carbonyl;
Z is nitro, cyano group, ester group, aldehyde radical, carboxyl, trifluoromethyl, trifluoroacetyl group, or trifyl.
2. acceptable salt on the optical isomer of compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science is characterized in that R
1Be selected from: the pyridyl, thiazolyl, pyrimidyl, tetrahydrofuran base, oxazolyl or its halides that replace or replace, wherein, described substituting group is to be selected from down one or more in organizing: halogen, C
1-4Haloalkyl or C
1-4Halogenated alkoxy.
3. acceptable salt on the optical isomer of compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science is characterized in that R
2, R
3Common formation-CH
2-CH
2-,-CH
2-CH
2-CH
2-or-CH
2-MRc-CH
2-, wherein M is the heteroatoms that is selected from down group: N, O or S; Rc is the saturated or unsaturated C on the heteroatoms
1-8Alkyl or alkoxyl group.
4. acceptable salt on the optical isomer of compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science is characterized in that, when X=N, and R
4Be H independently, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, saturated or unsaturated C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, carbobenzoxy, C
2-6Alkynyl-carbonyl, C
2-3Thiazolinyl-carbonyl, C
3-6Cycloalkyl-carbonyl, benzoyl; Perhaps by one or more halogen atom, saturated or unsaturated C of being selected from
1-8Alkyl, C
1-8Haloalkyl, C
1-8Alkoxyl group or C
1-8The benzoyl that the substituting group of alkyl-carbonyl replaces, furans carbonyl or N, N-dimethyl carbonyl; Perhaps be selected from phenyl ring, pyridine, naphthalene nucleus, thiazole, pyrimidine, furans, a kind of in the thiophene ， oxazole, quinoline fragrance (mixing) ring, above-mentioned fragrance (mixing) encircles optionally by halogen, itrile group, carboxyl, nitro, hydroxyl, methylamino, C
1-4Haloalkyl replaces.
5. acceptable salt on the optical isomer of compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science is characterized in that, when X=N, and R
4Also can be independently-YR
aR
bStructure, wherein Y is N, S, SO or SO independently
2
R
aAnd R
bBe H independently of one another, saturated or unsaturated C
1-8Alkyl, allyl group, phenyl, benzyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, or carbobenzoxy; Perhaps
R
aAnd R
bCommon formation-CH
2-CH
2-,-CH
2-CH
2-CH
2-or-CH
2-MRc-CH
2-, M is the heteroatoms that is selected from down group in the formula: N, O or S; Rc is the substituting group on the heteroatoms, is selected from H, saturated or unsaturated C
1-8Alkyl, allyl group, benzyl, phenyl, C
1-8Alkoxy-C
1-8Alkyl, C
1-8Alkoxyl group-carbonyl, or carbobenzoxy.
6. acceptable salt on the optical isomer of compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science is characterized in that, works as X=S, SO, or SO
2The time, R
4Do not exist.
7. acceptable salt on the optical isomer of compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science is characterized in that, m is 1～3 integer, and when m=1,
During m=2,
During m=3,
Wherein, above-mentioned various in, R
7, R
8, R
9, R
10, R
11, and R
12As defined in claim 1.
8. acceptable salt on the optical isomer of compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science is characterized in that R
5, R
6, R
7, R
8, R
9, R
10, R
11And R
12Be H independently of one another, halogen, saturated or unsaturated C
1-8Alkyl, C
1-8Saturated or unsaturated alkoxyl group, halo C
1-8Saturated or unsaturated alkoxyl group, C
1-8Alkyl-ester group (RCOO-), C
1-8Alkyl-sulphonyl ester group or fluoroform sulfonyl ester; Perhaps be phenyl ring, pyridine, naphthalene nucleus, furans or the quinoline of replacement, described substituting group is selected from down group: halogen, itrile group, nitro, hydroxyl, methylamino, carboxyl, dimethylin, saturated or unsaturated C
1-8Alkyl, C
1-8Alkoxyl group, C
1-8Haloalkyl, C
1-8Alkyl-carbonyl.
9. acceptable salt on the optical isomer of compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science is characterized in that, Z is nitro, cyano group, ester group, aldehyde radical, carboxyl, trifluoromethyl, trifluoroacetyl group, or trifyl.
10. agricultural composition, it comprises:
(a) acceptable salt or their combination on each described compound, its optical isomer, cis-trans-isomer or the Pesticide Science among the claim 1-9 of 0.0001-99.99 weight %; And
(b) acceptable carrier and/or vehicle on the Pesticide Science.
11. the purposes of agricultural composition as claimed in claim 10 is characterized in that, is used for killing or preventing the insect of Agricultural pests, sanitary insect pest and harm animal health; Or with acting on the insecticides of killing or prevent Agricultural pests, sanitary insect pest and harm animal health.
12. method for preparing the described agricultural composition of claim 10, it is characterized in that, comprise step: with acceptable salt or their combination on each described compound, its optical isomer, cis-trans-isomer or the Pesticide Science among (a) claim 1-9; Mix with acceptable carrier and/or vehicle on (b) Pesticide Science, thereby form agricultural composition.
13. a desinsection and/or insect protected method is characterized in that, comprise each described compound of claim 1-9 or the described composition of claim 10 are put in the plant materials that suffers or may insect infestation, animal body, soil or environment around it.
14. the purposes of acceptable salt or their combination on the optical isomer of a compound as claimed in claim 1 or described compound, cis-trans-isomer or the Pesticide Science, it is characterized in that, for the preparation of the insecticides that is used for killing or preventing Agricultural pests, sanitary insect pest and harm animal health.
15. the preparation method as acceptable salt on each described compound, its optical isomer, cis-trans-isomer or the Pesticide Science among the claim 1-9 is characterized in that, when X=N, comprises step:
In polar solvent, in the presence of the acid of catalytic amount, with compound W and R
4NH
2Inorganic acid salt or organic acid salt, react with formula A0 compound, formula B0 compound or formula C0 compound respectively, thereby obtain formula A1 compound respectively, formula B1 compound, or formula C1 compound;
Above-mentioned various in, R
1, R
2, R
3, R
4, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z as defined in claim 1.
16. the preparation method as acceptable salt on each described compound, its optical isomer, cis-trans-isomer or the Pesticide Science among the claim 1-9 is characterized in that, as X=S, SO or SO
2The time, comprise step:
(1) in polar solvent, with formula A ' compound, formula B ' compound or formula C ' compound and CH
3I reaction back, again and Na
2The S reaction, thus formula A2 compound, formula B2 compound or formula C2 compound obtained respectively;
Above-mentioned various in, R
1, R
2, R
3, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z as defined in claim 1;
(2) in inert solvent, with formula A2 compound, formula B2 compound or formula C2 compound and benzoyl hydroperoxide (mCPBA) reaction, thus obtain formula A3 compound, formula A4 compound, formula B3 compound, formula B4 compound respectively, formula C3 compound, formula C4 compound;
Above-mentioned various in, R
1, R
2, R
3, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12With Z as defined in claim 1, X
3=SO, X
4=SO
2
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Cited By (3)
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|---|---|---|---|---|
| CN105017257A (en) * | 2014-04-30 | 2015-11-04 | 华东理工大学 | Derivative of tetrahydroindeno-6-vinyl-1,3a-diazapentalene and preparation method and application thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105017257A (en) * | 2014-04-30 | 2015-11-04 | 华东理工大学 | Derivative of tetrahydroindeno-6-vinyl-1,3a-diazapentalene and preparation method and application thereof |
| CN105017257B (en) * | 2014-04-30 | 2017-05-24 | 华东理工大学 | Derivative of tetrahydroindeno-6-vinyl-1,3a-diazapentalene and preparation method and application thereof |
| CN105461724A (en) * | 2014-08-11 | 2016-04-06 | 华东理工大学 | Nitrogen-containing bridged ring compound having insect disinfestation activity, preparation and uses thereof |
| CN105461724B (en) * | 2014-08-11 | 2019-11-05 | 华东理工大学 | Nitrogenous endocyclic compound and its preparation and use with insecticidal activity |
| CN111165505A (en) * | 2020-02-24 | 2020-05-19 | 华东理工大学 | Use of eight-membered oxygen bridged heterocyclic compounds as bee selective insecticide synergists |
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