CN103923061A - Heterocyclic 1,4-pentadiene-3-ketoxime compound as well as preparation method and application thereof - Google Patents

Heterocyclic 1,4-pentadiene-3-ketoxime compound as well as preparation method and application thereof Download PDF

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CN103923061A
CN103923061A CN201410154762.7A CN201410154762A CN103923061A CN 103923061 A CN103923061 A CN 103923061A CN 201410154762 A CN201410154762 A CN 201410154762A CN 103923061 A CN103923061 A CN 103923061A
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pentadiene
phenyl
nitrae
isosorbide
compound
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薛伟
陈玉
张贤
王忠波
朱雪松
柳敏
夏丽娟
龚华玉
赵洪菊
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Guizhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The invention discloses a heterocyclic 1,4-pentadiene-3-ketoxime compound 1 as well as a preparation method and application thereof. X in a structural formula 1 is heteroatom O or S, R[1]O can be at the ortho-position and the para-position, and R1 and R2 are one-substituted or multi-substituted aryl and substituted heterocyclic group respectively and can be substituted with one or more groups. A series of heterocyclic 1,4-pentadiene-3-ketoxime compounds are prepared by introducing furan, thiophene and oxime ether active groups on the basis of curcumin derivatives, namely 1,4-pentadiene-3-ketone. A bioactivity test shows that the compounds have the effect of controlling crop pests and especially have a certain control effect on plutella xylostella and aphids; meanwhile, the compounds have a relatively good inhibition effect on tobacco mosaic viruses (TMV).

Description

Contain Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound of heterocycle and its preparation method and application
Technical field
The present invention relates to 1-aryl-5-heterocyclyl base-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound having desinsection and antiviral activity and preparation method thereof.
Background technology
The multiple biological activitys such as curcumine has desinsection, antibacterial, antiviral, anti-inflammatory is anti-oxidant, anticancer, its derivative Isosorbide-5-Nitrae-pentadiene-3-ketone compounds equally has biological activity widely with curcumine, but stability is better, and toxic side effect is less.Therefore, taking curcumine as lead compound, it is carried out to structural modification, expect to obtain more highly active Isosorbide-5-Nitrae-pentadiene-3-ketone compounds, synthesize theoretical support is provided for the design of green bionic pesticide.
Curcumin derivate and analogue Isosorbide-5-Nitrae-pentadiene-3-ketone compounds thereof the progress aspect desinsection, the biological activity such as antiviral, antibacterial is below mainly described.
Aspect desinsection: Zou Huaibo etc. (Zou Huaibo, Ding Wei, Zhou Gang. the synthetic and activity rating [J] of curcumine dinitrobenzene hydrazine derivative. agricultural University Of Southwest's journal (natural science edition), 2006, 8 (1): 58-60.) and synthesize curcumine 2,4 dinitrophenyl hydrazine derivative, preliminary activity research result shows: target compound has certain acaricidal activity.In the time of concentration 3 mg/mL, 24,48 and 72 h are respectively 67.6%, 91.3% and 99.3% to the lethality rate of carmine spider mite, better than the prevention effect of the curcumine of same concentration.Feng little Gui etc. (Feng little Gui, Ding Wei, Zhang Yongqiang. the synthetic and acaricidal activity evaluation [J] of curcumine therewith. southwestern Normal University's journal (natural science edition), 2007, 32 (3): 55-59.) synthesized a kind of phenyl hydrazones curcumin derivate with curcumine and phenylhydrazine, biological activity test shows: target compound to the contact toxicity of citrus red mite (crm) before 48 h higher than curcumine; Before 24 h, to the contact toxicity of carmine spider mite apparently higher than curcumine; Both are suitable to the contact toxicity of tyrophagus putrescentiae.2013, Luo Jinxiang etc. (Luo Jinxiang, Ding Wei, Zhang Yongqiang, Yang Zhenguo, Li Yang. the synthetic and acaricidal activity [J] of curcumine isoxazole and pyrazole derivatives. pesticide Science journal, 2013, 15 (4): 372-380.) and design synthesized the curcumin derivate of Han isoxazole and pyrazoles.Acaricidal activity test result shows: drug concentration is 1 × 10 -3when mol/L, compound shows good acaricidal activity to carmine spider mite and panonychus citri, all higher than curcumine; And the treatment time is longer, activity is higher.
At anti-virus aspect: El-Subbagh etc. (El-Subbagh, H. I.; Abu-Zaid, S. M.; Mahran, M. A.; Badria, M. A.; Al-Obaid, A.M.Synthesis and biological evaluation of certain α, β-unsaturated ketones and their corresponding fused pyridines as antiviral and cytotoxic agents [J]. journal of Medicinal Chemistry, 2000, 43 (15): 2915-2921.) synthesize and contained nisosorbide-5-Nitrae-pentadiene-3-ketone compound of-methylpiperidone, and target compound has been carried out in vitro antiviral activity screening.Result shows: compound has certain inhibition activity to anti-herpes simplex virus-1.Wang Zhen rather wait (Wang Zhenning, Hu Deyu, Song Baoan, Yang Song, Jin Linhong, Xue Wei. the synthetic and bioactivity research [J] of 1,5-disubstituted pyrazole base-Isosorbide-5-Nitrae-pentadiene-3-ketone compounds. organic chemistry, 2009, 29 (9): 1412-1418.) and taking curcumine as lead compound, design has been synthesized a series of 1,5-disubstituted pyrazole base-Isosorbide-5-Nitrae-pentadiene-3-ketone compounds, and it is carried out to the active testing of resisting tobacco mosaic virus.Result shows: part of compounds has good activity of resisting tobacco mosaic virus.Chou Qiujuan etc. (Chou Qiujuan, Xue Wei, Lu Ping, Wang Zhenchao, Wei Xue. containing the synthetic and antiviral activity [J] of oxime ester curcuminoids derivative. synthetic chemistry, 2011, 19 (1): 36-40; 77.) oxime ester is introduced to single carbonyl curcumin derivative 1, in 5-diaryl-Isosorbide-5-Nitrae-pentadiene-3-ketone structure, 11 asymmetric 1 are synthesized, 5-diaryl-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ester compound, has carried out cucumber-mosaic-virus resistant (CMV) test to target compound.Result shows: when concentration is 0.5 mg/L, all compounds have certain anti-CMV activity.
Aspect antibacterial: (Li Shaobo, Hu Deyu, Song Baoan, Yang Song, the Jin Linhong such as Li Shaobo, Xue Wei, Zeng Song, Wang Jun, Chen Zhuo, Lu Ping, Zhou Xia, Fan Linge. novel 1, the synthetic and bacteriostatic activity research [J] of 5-phenylbenzene-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ester compound. organic chemistry, 2008, 28 (2): 311-316.) oxime ester is incorporated in Isosorbide-5-Nitrae-pentadiene-3-ketone structure, obtain a series of Isosorbide-5-Nitrae-pentadienes-3-ketoxime lipoid substance.Bacteriostatic activity result shows: in the time that drug concentration is 50 mg/L, compound is 42 ~ 53% to the inhibiting rate of fusarium graminearum, capsicum wilt bacterium, Valsa mali, and to dislike the inhibition of mould spirit active quite with contrasting medicament.Sahu etc. are with (Sahu, Pramod K.; Sahu Praveen K.; Gupta S.K.; Thavaselvam, D.; Agarwal, D. D. Synthesis and evaluation of antimicrobial activity of 4H-pyrimido[2,1-b] benzothiazole, pyrazole and benzylidene derivatives of curcumin [J]. european Journal of Medicinal Chemistry, 2012, 54:366-378.) curcumine is raw material, respectively with replace hydrazine, substituted benzoyl aldehyde reaction, the curcumin derivate containing pyrazoles and benzylidene has been synthesized in design.Preliminary bacteriostatic activity data show: most compounds all has good bacteriostatic activity to bacteriums such as streptococcus aureus, Pseudomonas aeruginosa, salmonella typhi, intestinal bacteria, bacillus cereus and Providence bacterium, and all higher than curcumine, be 4 ~ 16 times of its bacteriostatic activity.(Lal, the J. such as Lal; Gupta, S. K.; Thavaselvam, D.; Agarwal, D. D. Biological activity, design, synthesis and structure activity relationship of some novel derivatives of curcumin containing sulfonamides [J]. european Journal of Medicinal Chemistry, 201364:579-588.) single carbonyl of curcumine is carried out to structural modification, the curcumin derivate containing benzsulfamide structure has been synthesized in design, bacteriostatic activity shows: it is active that compound has good inhibition to bacteriums such as streptococcus aureus, bacillus cereus, salmonella typhi, Pseudomonas aeruginosa and intestinal bacteria, and all activity are at least all 4 times of curcumine.
Advantages such as oximinoether has efficiently, low toxicity, low residue, and have desinsection, the multiple biological activity such as antibacterial, antiviral, the design of this compounds is synthetic has caused people's extensive concern with activity research.
Aspect desinsection: (Liu, the A. P. such as Liu Aiping; Ou, X. M.; Huang, M. Z.; Wang, X. G.; Liu, X. P.; Wang, Y. Q.; Chen, C.; Yao, J. R. Synthesis and insecticidal activities of novel oxime ether pyrethroids [J]. pest Management Science, 2005, 61:166 – 170.) and taking methyl phenyl ketone as raw material, the oximinoether containing pyrethroid has been synthesized in design, and target compound has been carried out to insecticidal activity test.Preliminary activity data shows: all compounds have good insecticidal activity to Homoptera insect and lepidopterous insects.Wherein, part of compounds shows good contact toxicity to rice green leafhopper, and its effect is 5-8 times of contrast medicament bromothalonil.Dai Hong etc. (wear red, Liu Jianbing, seedling literal arts, Wu Shanshan, Qin Xue, Zhang Xin, Wang Tingting. the novel synthetic and bioactivity research [J] containing the cyclosubstituted Pyrazole Oxime Esters of pyridine. organic chemistry, 2011, 31 (10): 1662-1667.) pass through nthe condensation reaction of-pyridyl pyrazoles oxime and CCMP, synthesized a series of cyclosubstituted Pyrazole Oxime Esters of pyridine that contain, insecticidal activity test result shows: part of compounds shows 50.3% kill ratio in the time that concentration is 500 μ g/mL to aphid.(Fu, the C. R. such as Fu; Pei, J.; Ning, Y.; Liu, M.; Shan, P. C.; Liu, J.; Li, Y. Q.; Hu, F. Z.; Zhu, Y. Q.; Yang, H. Z.; Zou, X. M. Synthesis and insecticidal activities of novel pyrazole oxime ether derivatives with different substituted pyridyl rings [J]. pest Management Science, 2013.) design and synthesized a series of Pyrazole Oxime Esters, and tested desinsection and the acaricidal activity of target compound.Preliminary activity data shows: majority of compounds has good desinsection and acaricidal activity.Wherein, in the time that drug concentration is 50 mg/L or 100 mg/L, part is 90% ~ 100% (contrast is 98%) to the lethality rate of bean aphid; Be 94% ~ 100% (contrast is 100%) to the effect of tagging of carmine spider mite.
At anti-virus aspect: (the Yang Song such as Yang Song, Song Baoan, Liu Xinhua, meet Li Li, Jin Linhong, Wang Hua, Hu Deyu, Liu Gang. 2-(benzothiazole-2-base sulfo-)-1-(2,3,4-trimethoxyphenyl) ethyl ketone oxime ester and oxime ether new compound are synthetic studies [J] with activity of resisting tobacco mosaic virus. organic chemistry, 2005, 25:1116-1120.) and synthetic 6 oximinoethers containing benzothiazole, biological activity test shows: most compounds has certain activity to tobacco mosaic virus (TMV).Structure activity relationship shows: R is that the compound activity of resisting tobacco mosaic virus of phenyl or fragrant heterocyclic substituted is better than the compound that alkyl replaces; Antiviral activity containing the compound of 4-Cl on phenyl ring is better.(Xue Wei, Song Baoan, the Wang Hua such as Xue Wei, He Wei, Yang Song, Jin Linhong, Hu Deyu, Liu Gang, Lu Ping. 2-[5-(3,4,5-trimethoxyphenyl)-1,3,4-thiadiazoles-2-base sulfo-]-1-(2,3,4-trimethoxy) acetophenone oxime ether synthesizes and activity of resisting tobacco mosaic virus is studied [J]. organic chemistry, 2006, 26 (5): 702-706.) and synthesize 2-[5-(3,4,5-trimethoxyphenyl)-1,3,4-thiadiazoles-2-base sulfo-]-1-(2,3,4-trimethoxy) acetophenone oxime ether compound.Biological activity test shows: compound all has certain resisting tobacco mosaic virus (TMV) activity.In the time that concentration is 500 mg/L, the activity of part of compounds is respectively 51.3%, 41.1%, has exceeded commodity antiviral agent DHT (30.0%), Ningnanmycin (40.9%), viral A (36.7%).
Aspect antibacterial: (Parthiban, the P. such as Parthiban; Aridoss, G.; Rathika, P.; Ramkumar, V.; Kabilan, S. Synthesis, spectral, crystal and antimicrobial studies of biologically potent oxime ethers of nitrogen, oxygen and sulfur heterocycles [J]. bioorganic & Medicinal Chemistry Letters, 2009, 19:2981 – 2985.) and synthesize the oximinoether of two classes containing hexa-member heterocycle, and target compound has been carried out to bacteriostatic activity test.Preliminary activity data shows: most compounds has good biological activity to common bacterium and fungi, and activity is 1 ~ 4 times of contrast.(Ma, the X. B. such as Ma; Yin, A. Q.; Xue, S. J. Synthesis, crystal structure and bioactivity of 1-(4-Methylbenzy1) piperidi-n-4-one O-(6-chloropyridin-3-y1) methyl oxime [J]. journal of Shanghai Normal University (Natural Sciences), 201140 (1): 41-46.) by the nucleophilic substitution reaction of 1-(4-methyl-benzyl) piperidin-4-one-oxime and CCMP, synthesized compound 1-(4-methyl-benzyl) piperidin-4-one--6-chloropyridine-3-methyloxime ether.Preliminary fungicidal activity test shows: be 1 × 10 in concentration -4when mg/L, this compound is respectively 85.71%, 76.52%, 84.25%, 85.00% and 65.45% to the inhibiting rate of reaping hook wilt, dry thread Pyrenomycetes, ash arrhizus bacteria, wheat scab and Colletotrichum truncatum.
Research is found: curcumin analogue Isosorbide-5-Nitrae-pentadiene-3-ketone compounds is the same with curcumine, has multiple biological activity, and it is carried out to structural modification, expects to improve its biological activity and utility value.In research in the past, (the Song Baoan such as Song Baoan, Wu Jian, Xue Wei, Chen Pengli, Yang Song, Zeng Song, Hu Deyu, Wang Zhenchao, Xu Weiming. 1,5-disubstituted aryl-1,4-pentadiene-3-ketoxime ether compound and preparation method thereof and insecticidal activity application [P]. CN:ZL201010272708.4,2012-06-27 :) synthetic a series of 1 of oxime ether structure, certain insecticidal activity that 5-disubstituted aryl-Isosorbide-5-Nitrae-pentadiene-3-ketone compounds has of containing, but do not relate to the antiviral activity of 1-phenyl-5-heterocyclic radical-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether.The present invention adopts active splicing principle, to there be higher active heterocycle and oxime ether to be incorporated in curcumin derivate pentadienone structure at desinsection, the aspect such as antiviral, antibacterial, the synthetic 1-aryl-5-heterocyclyl of design base-1,4-pentadiene-3-ketoxime ether compound, bioactivity research is found: this compounds has certain contact toxicity to small cabbage moth, aphid, has good resisting tobacco mosaic virus (TMV) activity simultaneously.
Summary of the invention
Object of the present invention, taking curcumine as lead compound, adopt active splicing principle, 1, in 4-pentadiene-3-ketone structure, introduce heterocycle and oxime ether, synthetic 1-aryl-5-heterocyclyl base-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound, and this compounds has been carried out to the desinsection such as small cabbage moth, aphid and activity of resisting tobacco mosaic virus test.Its compound structure general formula ( 1) as follows:
In formula, as the substituting group on phenyl ring, R 1o can be at ortho position or contraposition; R 1the benzyl replacing for benzyl or containing groups such as one or more halogen atoms, itrile group, nitros;
R 2for phenyl, the phenyl replacing containing one or more halogen atoms, itrile group, nitro, oh group; Pyridine ring, replaces containing one or more halogen atoms, itrile group, nitryl group; Described halogen atom is fluorine atom, chlorine atom, bromine atoms or iodine atom.
X is the heteroatomss such as nitrogen, oxygen, sulphur.
General formula be ( 1) compound small cabbage moth and aphid are had to certain insecticidal activity, there is good anti-TMV activity simultaneously.
Synthetic route is as follows:
The compound title of composite part is as follows:
Chloro-benzyl-the 1-[2-of 2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound a);
Chloro-benzyl-the 1-[2-of 2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound b);
Chloro-benzyl-the 1-[2-of 2,4-bis-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound c);
4-nitro-benzyl-1-[2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound d);
Chloro-benzyl-the 1-[2-of 2,4-bis-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound e);
4-methoxyl group-benzyl-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound f);
CMP-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound g);
Benzyl-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound h);
4-nitro-benzyl-1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound i);
CMP-1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound j);
CMP-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound k);
4-nitro-benzyl-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound l);
Benzyl-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound m);
Chloro-benzyl-the 1-[2-of 2,4-bis-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound n);
Fluoro-benzyl-the 1-[2-of 3-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound o).
Preparation method and the processing condition of the compounds of this invention 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether are:
The first step, the preparation of 4-(adjacent or to) hydroxy phenyl-3-butene-2-one
The phenyl aldehyde that monohydroxy is replaced joins in acetone, stirs, and drips 5% aqueous sodium hydroxide solution under ice bath, and reaction solution becomes burgundy clear liquid from faint yellow clear liquid.After reaction finishes, slowly drip dilute hydrochloric acid solution under condition of ice bath, have faint yellow solid to produce, filter, washing, dries, and uses acetone/water recrystallization, obtains faint yellow solid.
The ratio of amount of substance, monosubstituted hydroxy aldehyde: acetone: sodium hydroxide=1:30:2.2 ~ 2.5
Temperature of reaction: 20 ~ 24 DEG C
Reaction times: 10 ~ 30 h
This step is applicable to the synthetic of all above-mentioned 4-(adjacent or to) hydroxy phenyl-3-butene-2-one;
Second step, the preparation of 1-(adjacent or to) hydroxy phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone
By 4-(adjacent or to) hydroxy phenyl-3-butene-2-one and heterocyclic aldehydes, be dissolved in dehydrated alcohol, stir, under condition of ice bath, be added dropwise to 5% aqueous sodium hydroxide solution, reaction solution becomes burgundy clear liquid from faint yellow clear liquid.After question response is complete, under condition of ice bath, slowly drip dilute hydrochloric acid solution, have faint yellow solid to produce, filter, wash, dry, with dehydrated alcohol/water recrystallization, obtain light yellow crystal.
The ratio of amount of substance, 4-(adjacent or to) hydroxy phenyl-3-butene-2-one: sodium hydroxide: heterocyclic aldehydes=1.1:2.5:1
Temperature of reaction: 20 ~ 25 DEG C
Reaction times: 15 ~ 20 h
This step is applicable to the synthetic of all above-mentioned 1-(adjacent or to) hydroxy phenyl-5-heterocyclic radical-Isosorbide-5-Nitrae-pentadiene-3-ketone;
The 3rd step, the preparation of 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone
1-(adjacent or to) hydroxy phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone, Anhydrous potassium carbonate, potassiumiodide are dissolved in acetone, stir, drip the acetone soln that contains (replacement) benzyl chlorine, reflux.After reaction finishes, be chilled to room temperature, filter, revolve and steam except desolventizing, ethanol or acetone recrystallization, obtain yellow crystals.
The ratio of amount of substance, 1-(adjacent or to) hydroxy phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone: (replacement) benzyl chlorine: Anhydrous potassium carbonate: potassiumiodide=1:1.2:1.5:0.3 temperature of reaction: 50 ~ 60 DEG C
Reaction times: 4-8 h
This step is applicable to the synthetic of all above-mentioned 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone;
The 4th step, the preparation of 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime
1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone, oxammonium hydrochloride are added in dehydrated alcohol, stir, drip pyridine; Under room temperature, stir, solution becomes yellow clear liquid from suspension, reacts completely, rotary evaporation is except desolventizing, add methylene dichloride, drip 5% dilute hydrochloric acid (volume ratio), regulate pH value to be about 5 ~ 6, washing, anhydrous sodium sulfate drying, filters precipitation, obtain yellow viscous fluid, column chromatography for separation obtains pale yellow powder.
The ratio of amount of substance, 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone: oxammonium hydrochloride: pyridine=1:2.5:30
Temperature of reaction: 20 ~ 25 DEG C
Reaction times: 40 ~ 50 h
This step is applicable to the synthetic of all above-mentioned 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime;
The 5th step, target compound substituted-phenyl or heterocyclic radical-1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3
Synthesizing of ketoxime ether
1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime, Anhydrous potassium carbonate are dissolved in dry acetonitrile, stir, drip and contain the anhydrous acetonitrile that replaces benzyl chlorine, reflux.After reaction finishes, be chilled to room temperature,
Filter, concentrated filtrate, obtains brown oil, adds methylene dichloride, saturated common salt washing, and anhydrous sodium sulfate drying, filters, precipitation, column chromatography for separation obtains target compound.
The ratio of amount of substance, 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime: salt of wormwood: benzyl chlorine=1:2:1.2
Temperature of reaction: 75 ~ 85 DEG C
Reaction times: 2-6 h
This step is applicable to the synthetic of all above-mentioned substituted-phenyls or heterocyclic radical-1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3 ketoxime ether.
The application of the compound described in any one of the present invention, is characterized in that as sterilant and antiviral agent.
The present invention is taking curcumine as lead compound, adopt active splicing principle, 1, in 4-pentadiene-3-ketone structure, introduce heterocycle and oxime ether, synthetic 1-aryl-5-heterocyclyl base-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound, and this compounds has been carried out to the desinsection such as small cabbage moth, aphid and anti-TMV active testing, find that it has good contact toxicity to small cabbage moth and aphid, there is good anti-TMV activity simultaneously.
Embodiment
Chloro-benzyl-the 1-[2-of embodiment mono-, 2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound a):
(1) 4-(2-hydroxy phenyl)-3-butene-2-one is synthetic
In the three-necked bottle of 500 mL, add successively salicylaldhyde 7.33 g (60 mmol), acetone 60 mL, are stirred to molten; Under condition of ice bath, slowly drip approximately 5% sodium hydroxide solution 100 mL (132 mmol sodium hydroxide); Stirring at room temperature, TLC following response, volume ratio, sherwood oil: ethyl acetate=2:1, after reaction 10 h, drips dilute hydrochloric acid to solution colour and no longer changes (pH is about 5), has yellow solid to separate out, and leaves standstill a night, and suction filtration, dries naturally, obtains yellow solid.Productive rate: 89%; Fusing point: 139-141 DEG C.
(2) preparation of 1-(2-hydroxy phenyl)-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone
Get 3.57 g 4-o-hydroxy-phenyl-3-butene-2-one (22 mmol), 2.24 g 2 thiophene carboxaldehydes (20 mmol), 40 mL ethanol add in 250 mL three-necked bottles successively, are stirred to molten; Under condition of ice bath, slowly drip 40 mL approximately 5% sodium hydroxide solutions (50 mmol sodium hydroxide); Stirring at room temperature, TLC following response.React after 16 h, under ice bath, drip dilute hydrochloric acid to solution colour and no longer change (pH is about 5), have yellow mercury oxide to generate, leave standstill, suction filtration, ethanol/water recrystallization, obtains yellow crystals.Productive rate: 72%; Fusing point: 153-155 DEG C.
(3) 1-[2-(3-fluorine benzyloxy) phenyl] preparation of-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone
In 100 mL three-necked bottles, add successively 1.28 g 1-o-hydroxy-phenyl-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone (5 mmol), 1.04 g K 2cO 3(7.5 mmol), 0.25 g KI (1.50 mmol), 20 mL acetone, stir; Drip acetone 5 mL containing 0.87 g 3-fluorine benzyl chlorine (6.00 mmol), reflux; TLC following response, volume ratio, sherwood oil: ethyl acetate=3:1, reaction finishes 4.5 h, is cooled to room temperature; Filter, filtrate is revolved to steam and is removed acetone, and ethyl alcohol recrystallization, obtains yellow needle-like crystal.Productive rate: 79%; Fusing point: 116-117 DEG C.
(4) 1-[2-(3-fluorine benzyloxy) phenyl] preparation of-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime
In 100 mL three-necked bottles, add successively 3.64 g 1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-1,4-pentadiene-3-ketone (10 mmol), 1.39 g oxammonium hydrochlorides (20 mmol), 40 mL ethanol, stir lower drip 20 mL pyridines, stirring at room temperature 48 h, TLC following response, volume ratio, sherwood oil: ethyl acetate: CH 2cl 2=2:1:1, obtains yellow clear liquid.Revolve and steam except desolventizing, add 20 mLCH 2cl 2, dilute hydrochloric acid adjusts pH to be about 5, washes anhydrous sodium sulfate drying six times; Filter, concentrated, column chromatography for separation is purified and is obtained white powder.Productive rate: 53%; Fusing point: 128-131 DEG C.
(5) the chloro-benzyl-1-[2-of 2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether synthetic
In 50 mL three-necked bottles, add successively 0.57 g 1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime (1.5 mmol), 0.41 g anhydrous K 2cO 3(3 mmol), 10 mL anhydrous acetonitriles, stir lower anhydrous acetonitrile 4 mL that contain 0.29 g 2-benzyl chloride chlorine (1.2 mmo) that drip, and are warming up to backflow; TLC following response, volume ratio, sherwood oil: ethyl acetate=4:1, after reaction 3 h, is cooled to room temperature, filters, and concentrated filtrate, obtains oily matter, adds 10 mL CH 2cl 2, saturated common salt water washing (25 mL × 4), anhydrous sodium sulfate drying, filters, concentrated, and column chromatography for separation is purified, and obtains brown dope.Productive rate: 48%.
Embodiment bis-, 4-nitro-benzyl-1-[2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound d):
(1) 4-(2-hydroxy phenyl)-3-butene-2-one is synthetic
As synthetic in embodiment mono-(1) method and condition.
(2) preparation of 1-(2-hydroxy phenyl)-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone
As synthetic in embodiment mono-(2) method and condition.
(3) 1-[2-(benzyloxy) phenyl] preparation of-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone
In 100 mL three-necked bottles, add successively 1.28 g 1-o-hydroxy-phenyl-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone (5 mmol), 1.04 g K 2cO 3(7.5 mmol), 0.25 g KI (1.50 mmol), 20 mL acetone, stir; Drip acetone 5 mL containing 0.76 g benzyl chlorine (6.00 mmol), reflux; TLC following response, volume ratio, sherwood oil: ethyl acetate=3:1, reaction finishes 5 h, is cooled to room temperature; Filter, filtrate is revolved to steam and is removed acetone, and ethyl alcohol recrystallization, obtains yellow needle-like crystal.Productive rate: 82%; Fusing point: 91-92 DEG C.
(4) 1-[2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime synthetic
In 100 mL three-necked bottles, add successively 3.46 g 1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-1,4-pentadiene-3-ketone (10 mmol), 1.39 g oxammonium hydrochlorides (20 mmol), 40 mL ethanol, stir lower drip 20 mL pyridines, stirring at room temperature 40 h, TLC following response, volume ratio, sherwood oil: ethyl acetate: CH 2cl 2=2:1:1, obtains yellow clear liquid.Revolve and steam except desolventizing, add 20 mLCH 2cl 2, dilute hydrochloric acid adjusts pH to be about 5, washes anhydrous sodium sulfate drying six times; Filter, concentrated, column chromatography for separation is purified and is obtained pale yellow powder.Productive rate: 49%; Fusing point: 118-121 DEG C.
(5) 4-nitro-benzyl-1-[2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether synthetic
In 50 mL three-necked bottles, add successively 0.54 g 1-[2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime (1.5 mmol), 0.41 g anhydrous K 2cO 3(3 mmol), 10 mL anhydrous acetonitriles, stir lower anhydrous acetonitrile 4 mL that contain 0.33 g 4-nitrobenzyl chlorine (1.2 mmo) that drip, and are warming up to backflow; TLC following response, volume ratio, sherwood oil: ethyl acetate=4:1, after reaction 6 h, is cooled to room temperature, filters, and concentrated filtrate, obtains oily matter, adds 10 mL CH 2cl 2, saturated common salt water washing (25 mL × 4), anhydrous sodium sulfate drying, filters, concentrated, and column chromatography for separation is purified, and obtains white powder.Productive rate: 41%, fusing point: 86-88 DEG C.
Embodiment tri-, 4-nitro-benzyl-1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound i):
(1) 4-(4-hydroxy phenyl)-3-butene-2-one is synthetic
In the three-necked bottle of 500 mL, add successively 4-hydroxy benzaldehyde 7.33 g (60 mmol), acetone 60 mL, are stirred to molten; Under condition of ice bath, slowly drip approximately 5% sodium hydroxide solution 110 mL (150 mmol sodium hydroxide, 110 mL water); Stirring at room temperature, TLC following response, volume ratio, sherwood oil: ethyl acetate=2:1, after reaction 16 h, drips dilute hydrochloric acid to solution colour and no longer changes (pH is about 5), has yellow solid to separate out, and leaves standstill a night, and suction filtration, dries naturally, obtains yellow powder.Productive rate: 80%; Fusing point: 96-98 DEG C.
(2) preparation of 1-(4-hydroxy phenyl)-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketone
Get 3.57 g 4-(4-hydroxy phenyl)-3-butene-2-one (22 mmol), 1.92 g 2 furan carboxyaldehydes (20 mmol), 40 mL ethanol add in 250 mL three-necked bottles successively, are stirred to molten; Under condition of ice bath, slowly drip 40 mL approximately 5% sodium hydroxide solutions (50 mmol sodium hydroxide); Stirring at room temperature, TLC following response.React after 16 h, under ice bath, drip dilute hydrochloric acid to solution colour and no longer change (pH is about 5), have yellow mercury oxide to generate, leave standstill, suction filtration, ethanol/water recrystallization, obtains yellow crystals.Productive rate: 69%; Fusing point: 162-163 DEG C.
(3) 1-[4-(benzyloxy) phenyl] preparation of-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketone
In 100 mL three-necked bottles, add successively 1.20 g 1-(4-hydroxy phenyl)-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketone (5 mmol), 1.04 g K 2cO 3(7.5 mmol), 0.25 g KI (1.50 mmol), 20 mL acetone, stir; Drip acetone 5 mL containing 0.76 g benzyl chlorine (6.00 mmol), reflux; TLC following response, volume ratio, sherwood oil: ethyl acetate=3:1, reaction finishes 5 h, is cooled to room temperature; Filter, filtrate is revolved to steam and is removed acetone, and ethyl alcohol recrystallization, obtains yellow needle-like crystal.Productive rate: 86%; Fusing point: 100-101 DEG C.
(4) 1-[4-(benzyloxy) phenyl] preparation of-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime
In 100 mL three-necked bottles, add successively 3.30 g 1-[4-(benzyloxy) phenyl]-5-(2-furans)-1,4-pentadiene-3-ketone (10 mmol), 1.39 g oxammonium hydrochlorides (20 mmol), 40 mL ethanol, stir lower drip 20 mL pyridines, stirring at room temperature 48 h, TLC following response, volume ratio, sherwood oil: ethyl acetate: CH 2cl 2=2:1:1, obtains the yellow stillness of night.Revolve and steam except desolventizing, add 20 mLCH 2cl 2, dilute hydrochloric acid adjusts pH to be about 5, washes anhydrous sodium sulfate drying six times; Filter, concentrated, column chromatography for separation is purified and is obtained pale yellow powder.Productive rate: 50%; Fusing point: 125-126 DEG C.
(5) 4-nitro-benzyl-1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether:
In 50 mL three-necked bottles, add successively 0.52 g 1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime (1.5 mmol), 0.41 g anhydrous K 2cO 3(3 mmol), 10 mL anhydrous acetonitriles, stir lower anhydrous acetonitrile 4 mL that contain 0.33 g 4-nitrobenzyl chlorine (1.2 mmo) that drip, and are warming up to backflow; TLC following response, volume ratio, sherwood oil: ethyl acetate=4:1, after reaction 4 h, is cooled to room temperature, filters, and concentrated filtrate, obtains oily matter, adds 10 mL CH 2cl 2, saturated common salt water washing (25 mL × 4), anhydrous sodium sulfate drying, filters, concentrated, and column chromatography for separation is purified, and obtains brown dope, productive rate: 31%.
Embodiment tetra-, CMP-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound k):
(1) 4-(4-hydroxy phenyl)-3-butene-2-one is synthetic
As synthetic in embodiment tri-(1) methods and condition.
(2) preparation of 1-(4-hydroxy phenyl)-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone
Get 3.57 g 4-(4-hydroxy phenyl)-3-butene-2-one (22 mmol), 2.24 g 2 thiophene carboxaldehydes (20 mmol), 40 mL ethanol add in 250 mL three-necked bottles successively, are stirred to molten; Under condition of ice bath, slowly drip 40 mL approximately 5% sodium hydroxide solutions (50 mmol sodium hydroxide); Stirring at room temperature, TLC following response.React after 16 h, under ice bath, drip dilute hydrochloric acid to solution colour and no longer change (pH is about 5), have yellow mercury oxide to generate, leave standstill, suction filtration, ethanol/water recrystallization, obtains yellow crystals.Productive rate: 68%; Fusing point: 207-209 DEG C.
(3) 1-[4-(3-fluorine benzyloxy) phenyl] preparation of-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone
In 100 mL three-necked bottles, add successively 1.28 g 1-(4-hydroxy phenyl)-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketone (5 mmol), 1.04 g K 2cO 3(7.5 mmol), 0.25 g KI (1.50 mmol), 20 mL acetone, stir; Drip acetone 5 mL containing 0.87 g 3-fluorine benzyl chlorine (6.00 mmol), reflux; TLC following response, volume ratio, sherwood oil: ethyl acetate=3:1, reaction finishes 4.5 h, is cooled to room temperature; Filter, filtrate is revolved to steam and is removed acetone, and ethyl alcohol recrystallization, obtains yellow needle-like crystal.Productive rate: 82%; Fusing point: 122-124 DEG C.
(4) 1-[4-(3-fluorine benzyloxy) phenyl] preparation of-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime
In 100 mL three-necked bottles, add successively 3.64 g 1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-1,4-pentadiene-3-ketone (10 mmol), 1.39 g oxammonium hydrochlorides (20 mmol), 40 mL ethanol, stir lower drip 20 mL pyridines, stirring at room temperature 48 h, TLC following response, volume ratio, sherwood oil: ethyl acetate: CH 2cl 2=2:1:1, obtains the yellow stillness of night.Revolve and steam except desolventizing, add 20 mLCH 2cl 2, dilute hydrochloric acid adjusts pH to be about 5, washes anhydrous sodium sulfate drying six times; Filter, concentrated, column chromatography for separation is purified and is obtained white powder.Productive rate: 51%; Fusing point: 131-133 DEG C.
(5) CMP-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether synthetic:
In 50 mL three-necked bottles, add successively 0.57 g 1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime (1.5 mmol), 0.41 g anhydrous K 2cO 3(3 mmol), 14 mL anhydrous acetonitriles, stir, and add 0.29 g CCMP (1.2 mmo), are warming up to backflow; TLC following response, volume ratio, sherwood oil: ethyl acetate=4:1, after reaction 3.5 h, is cooled to room temperature, filters, and concentrated filtrate, obtains oily matter, adds 10 mL CH 2cl 2, saturated common salt water washing (25 mL × 4), anhydrous sodium sulfate drying, filters, concentrated, and column chromatography for separation is purified, and obtains brown dope.Productive rate: 52%.
Embodiment five, 2, the chloro-benzyl-1-[2-of 4-bis-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound n):
(1) 4-(2-hydroxy phenyl)-3-butene-2-one is synthetic
As synthetic in embodiment mono-(1) method and condition.
(2) preparation of 1-(2-hydroxy phenyl)-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketone
Get 3.57 g 4-(2-hydroxy phenyl)-3-butene-2-one (22 mmol), 1.92 g 2 furan carboxyaldehydes (20 mmol), 40 mL ethanol add in 250 mL three-necked bottles successively, are stirred to molten; Under condition of ice bath, slowly drip 40 mL approximately 5% sodium hydroxide solutions (50 mmol sodium hydroxide); Stirring at room temperature, TLC following response.React after 16 h, under ice bath, drip dilute hydrochloric acid to solution colour and no longer change (pH is about 5), have yellow mercury oxide to generate, leave standstill, suction filtration, ethanol/water recrystallization, obtains yellow crystals.Productive rate: 70%; Fusing point: 164-166 DEG C.
(3) 1-[2-(benzyloxy) phenyl] preparation of-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketone
In 100 mL three-necked bottles, add successively 1.20 g 1-(2-hydroxy phenyl)-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketone (5 mmol), 1.04 g K 2cO 3(7.5 mmol), 0.25 g KI (1.50 mmol), 20 mL acetone, stir; Drip acetone 5 mL containing 0.76 g benzyl chlorine (6.00 mmol), reflux; TLC following response, volume ratio, sherwood oil: ethyl acetate=3:1, reaction finishes 5 h, is cooled to room temperature; Filter, filtrate is revolved to steam and is removed acetone, and ethyl alcohol recrystallization, obtains yellow needle-like crystal.Productive rate: 87%; Fusing point: 92-93 DEG C.
(4) 1-[4-(benzyloxy) phenyl] preparation of-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime
In 100 mL three-necked bottles, add successively 3.30 g 1-[2-(benzyloxy) phenyl]-5-(2-furans)-1,4-pentadiene-3-ketone (10 mmol), 1.39 g oxammonium hydrochlorides (20 mmol), 40 mL ethanol, stir lower drip 20 mL pyridines, stirring at room temperature 48 h, TLC following response, volume ratio, sherwood oil: ethyl acetate: CH 2cl 2=2:1:1, obtains the yellow stillness of night.Revolve and steam except desolventizing, add 20 mLCH 2cl 2, dilute hydrochloric acid adjusts pH to be about 5, washes anhydrous sodium sulfate drying six times; Filter, concentrated, column chromatography for separation is purified and is obtained pale yellow powder.Productive rate: 57%; Fusing point: 103-104 DEG C.
Chloro-benzyl-the 1-[2-of (5) 2,4-bis-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether synthetic:
In 50 mL three-necked bottles, add successively 0.52 g 1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime (1.5 mmol), 0.41 g anhydrous K 2cO 3(3 mmol), 10 mL anhydrous acetonitriles, stir lower dropping containing 0.35 g 2, and anhydrous acetonitrile 4 mL of the chloro-benzyl chlorine of 4-bis-(1.2 mmo), are warming up to backflow; TLC following response, volume ratio, sherwood oil: ethyl acetate=4:1, after reaction 2 h, is cooled to room temperature, filters, and concentrated filtrate, obtains oily matter, adds 10 mL CH 2cl 2, saturated common salt water washing (25 mL × 4), anhydrous sodium sulfate drying, filters, concentrated, and column chromatography for separation is purified, and obtains pale yellow powder, productive rate: 50%, fusing point: 100-103 DEG C.
Utilize similar synthetic method, synthetic 1-aryl-5-heterocyclyl base-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound structure as table 1shown in.
table 1the part of compounds structural formula of synthesized
Numbering Target compound structural formula Numbering Target compound structural formula
A B
C D
E F
G H
I J
K L
M N
O
Under the spectral data institute of synthetic part substituted-phenyl or heterocyclic radical-1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound:
Chloro-benzyl-the 1-[2-of 2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound a):
Brown dope, yield 48%; IR (KBr, cm -1): n max3067,3032,2930,1616,1595,1489,1449,1362,1240,1034,1016,962,750,698; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.69 ~ 7.59 (m, 2H, Ar (Cl)-3-H, tiophene-5-H), 7.53 ~ 7.21 (m, 11H, Ar (OCH 2)-4,6-H, Ar (Cl)-4,5,6-H, Ar (F)-4,5,6-H, Ar (OCH 2)-CH=, tiophene-CH=, tiophene-4-H), 7.18 ~ 6.98 (m, 5H, tiophene-C=CH, Ar (OCH 2)-C=CH, tiophene-3-H, Ar (OCH 2)-5-H, Ar (F)-2-H), 6.73 ~ 6.70 (d, j=16.0 Hz, 1H, Ar (OCH 2)-3-H), 5.35 ~ 5.33 (d, j=6.3 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer), 5.22 ~ 5.20 (d, j=8.6 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 156.6,156.3,154.4,154.1,141.7; 135.9,132.5,130.4,130.1,129.9; 129.3,128.0,127.6,127.1,126.0; 125.7,125.4,123.2,122.0; 121.4,117.5,116.0,114.6; 114.2,112.8,77.4,69.3; MS (ESI, m/z): 504.2 [M+ H] +.
Chloro-benzyl-the 1-[2-of 2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound b):
Brown dope, yield 37%; IR (KBr, cm -1): n max3065,3030,2932,1595,1489,1449,1362,1240,1059,1015,962,748,696; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.69 ~ 7.62 (m, 2H, Ar (Cl)-3-H, tiophene-5-H), 7.52 ~ 7.49 (m, 3H, Ar (OCH 2)-6-H, Ar-2,6-H), 7.45 ~ 7.42 (m, 3H, Ar (Cl)-4-H, tiophene-CH=, Ar (OCH 2)-CH=), 7.37 ~ 7.27 (m, 7H, Ar-3,4,5-H, Ar (Cl)-5,6-H, Ar (OCH 2)-4-H, tiophene-4-H), 7.21 ~ 7.14 (m, 2H, tiophene-C=CH, Ar (OCH 2)-C=CH), 7.07 ~ 7.05 (m, 1H, tiophene-3-H), 7.03 ~ 7.00 (m, 1H, Ar (OCH 2)-5-H), 6.73 ~ 6.69 (d, j=16.0 Hz, 1H, Ar (OCH 2)-3-H), 5.33 (s, 2H, CH 2), 5.20 (s, 2H, CH 2); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 156.9,154.5,141.8,137.2,135.9,132.7,132.6,130.5,129.9; 129.3,128.6,128.2,128.0,127.9,127.6,127.5,127.1; 126.0,125.3,121.5,121.2,117.3,112.9,77.4,70.0; MS (ESI, m/z): 486.3 [M+ H] +, 508.2 [M+Na] +.
Chloro-benzyl-the 1-[2-of 2,4-bis-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound c):
Yellow crystals, yield 58%, 129 ~ 131 ° of C of m.p.; IR (KBr, cm -1): n max1616,1589,1558,1489,1450,1381,1314,1250,1109,1072,1043,961,908,854,837,814,775,754,716,679; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.71 ~ 7.70 (d, j=6.3 Hz, 1H, Ar (Cl)-3-H), 7.65 ~ 7.61 (d, j=17.2 Hz, 1H, tiophene-5-H), 7.52 ~ 7.50 (m, 2H, Ar (OCH 2)-6-H, Ar (F)-5-H), 7.46 ~ 7.35 (m, 7H, tiophene-CH=, Ar (OCH 2)-CH=, Ar (F)-4,6-H, Ar (Cl)-5,6-H, Ar (OCH 2)-4-H), 7.30 ~ 7.28 (d, j=9.7 Hz, 1H, tiophene-4-H), 7.20 ~ 7.16 (m, 2H, tiophene-C=CH, Ar (OCH 2)-C=CH), 7.07 ~ 7.02 (m, 3H, tiophene-3-H, Ar (OCH 2)-5-H, Ar (F)-2-H), 6.73 ~ 6.69 (d, j=16.0 Hz, 1H, Ar (OCH 2)-3-H), 5.30 (s, 2H, CH 2), 5.26 (s, 2H, CH 2); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 156.7,154.6,141.7,140.2,135.1; 133.7,133.6,132.7,131.1,130.5; 128.9,128.2,128.0,127.7; 126.1,125.3,123.2,121.3; 117.4,114.7,114.5,114.2; 114.1,112.9,72.7,69.3; MS (ESI, m/z): 538.2 [M+ H] +.
4-nitro-benzyl-1-[2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound d):
white powder, yield 41%, 86 ~ 88 ° of C of m.p., IR (KBr, cm -1): n max3065,2849,1599,1514,1450,1345,1246,1107,1064,959,908,858,752,733,692, 1H NMR (500 MHz, CD3COCD3, ppm) δ: 8.25 ~ 8.22 (m, 2H, Ar (NO2)-3, 5-H), 7.72 ~ 7.60 (m, 4H, tiophene-5-H, Ar (NO2)-2, 6-H, Ar (OCH2)-6-H), 7.57 ~ 7.43 (m, 4H, Ar-2, 6-H, tiophene-CH=, Ar (OCH2)-CH=), 7.38 ~ 7.26 (m, 5H, Ar-3, 4, 5-H, Ar (OCH2)-4-H, tiophene-4-H), 7.20 ~ 7.11 (m, 2H, tiophene-C=CH, Ar (OCH2)-C=CH), 7.08 ~ 6.98 (m, 2H, tiophene-3-H, Ar (OCH2)-5-H), 6.72 ~ 6.69 (d, j=16.0 Hz, 1H, Ar (OCH2)-3-H), 5.39,5.37 (s, 2H, CH2, e-oxime isomer+ z-oxime isomer), 5.23,5.20 (s, 2H, CH2, e-oxime isomer+ z-oxime isomer), 13C NMR (125 MHz, CD3COCD3, ppm) δ: 157.0,154.7,146.5,141.7,137.3, 132.9,130.5,129.6,128.5,128.4, 128.3,128.2,128.0,127.9, 127.6,127.2,126.1,125.3, 123.5,121.3,121.2,117.3, 115.9,113.0,74.8,70.2, MS (ESI, m/z): 497.3 [M+ H] +, 519.3 [M+Na] +.
Chloro-benzyl-the 1-[2-of 2,4-bis-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound e):
White powder, yield 40%, 93 ~ 96 ° of C of m.p.; IR (KBr, cm -1): n max3030,2860,1628,1597,1489,1474,1450,1381,1362,1339,1238,1109,1074,1045,961,748,694; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.70 ~ 7.65 (m, 1H, Ar (Cl)-3-H), 7.61 ~ 7.58 (d, j=16.6 Hz, 1H, tiophene-5-H), 7.55 ~ 7.50 (m, 4H, Ar (OCH 2)-6-H, Ar (Cl)-5-H, Ar-2,6-H), 7.47 ~ 7.25 (m, 7H, tiophene-CH=, Ar (OCH 2)-CH=, Ar-3,4,5-H, Ar (Cl)-6-H, Ar (OCH 2)-4-H), 7.19 ~ 7.08 (m, 3H, tiophene-4-H, tiophene-C=CH, Ar (OCH 2)-C=CH), 7.03 ~ 6.98 (m, 2H, tiophene-3-H, Ar (OCH 2)-5-H), 6.72 ~ 6.69 (d, j=16.0 Hz, 1H, Ar (OCH 2)-3-H), 5.32 ~ 5.30 (d, j=10.3 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer), 5.22 ~ 5.20 (d, j=10.9 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 156.6,154.4,141.6,137.3,135.1,133.8,131.3,130.6,129.9; 129.6,129.0,128.6,128.2,127.9,127.5,127.3,127.2; 127.1,125.5,121.7,121.1,116.0,112.8,72.7,70.1; MS (ESI, m/z): 520.2 [M+ H] +, 542.2 [M+Na] +.
4-methoxyl group-benzyl-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound f):
White powder, yield 33%, 93 ~ 96 ° of C of m.p.; IR (KBr, cm -1): n max2934,2835,1616,1595,1516,1489,1448,1371,1302,1254,1238,1109,1015,953,779,750,706; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.72 ~ 7.71 (d, j=6.3 Hz, 1H, tiophene-5-H), 7.62 ~ 7.59 (d, j=16.6 Hz, 1H, Ar (OCH 2)-6-H), 7.51 ~ 7.50 (d, j=4.6 Hz, 1H, Ar (F)-5-H), 7.44 ~ 7.30 (m, 7H, Ar (F)-4,6-H, tiophene-CH=, Ar (OCH 2)-CH=, Ar (OCH 2)-4-H, tiophene-C=CH, tiophene-4-H), 7.22 ~ 7.21 (d, j=3.4 Hz, 1H, Ar (OCH 2)-C=CH), 7.15 ~ 7.13 (d, j=8.0 Hz, 2H, tiophene-3-H, Ar (OCH 2)-5-H), 7.10 ~ 7.07 (m, 2H, Ar (OCH 3)-2,6-H), 7.04 ~ 7.00 (m, 2H, Ar (OCH 3)-3,5-H), 6.92 ~ 6.91 (m, 2H, Ar (F)-2-H, Ar (OCH 2)-3-H), 5.25 (s, 2H, CH 2), 5.16,5.14 (s, 2H, CH 2, e-oxime isomer+ z-oxime isomer), 3.79 (s, 3H, OCH 3); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 159.7,156.3,153.1,141.7,130.5; 130.1,129.9,129.7,129.3,128.7; 128.1,127.1,126.9,125.8,123.2; 122.2,121.3,116.2,114.6; 114.5,114.2,114.0,113.7; 112.8,76.2,69.3,54.7; MS (ESI, m/z): 500.3 [M+ H] +, 522.3 [M+Na] +.
CMP-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound g):
Yellow oil, yield 40%; IR (KBr, cm -1): n max3067,2930,2872,1616,1591,1489,1458,1387,1240,1105,1016,964,750,704; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 8.56 ~ 8.53 (d, j=12.6 Hz, 1H, pyridine-6-H), 7.95 ~ 7.89 (m, 1H, pyridine-4-H), 7.75 ~ 7.73 (d, j=7.4 Hz, 1H, tiophene-5-H), 7.69 ~ 7.65 (m, 1H, Ar (OCH 2)-6-H), 7.56 ~ 7.28 (m, 8H, Ar (F)-4,5,6-H, tiophene-CH=, Ar (OCH 2)-CH=, pyridine-3-H, Ar (OCH 2)-4-H, tiophene-4-H), 7.23 ~ 7.06 (m, 5H, tiophene-C=CH, Ar (OCH 2)-C=CH, tiophene-3-H, Ar (OCH 2)-5-H, Ar (F)-2-H), 6.80 ~ 6.76 (d, j=16.0 Hz, 1H, Ar (OCH 2)-3-H), 5.34 ~ 5.32 (d, j=6.8 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer), 5.26 (s, 2H, CH 2); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 156.7,154.6,150.5,149.6,141.7; 139.2,133.3,132.6,130.5,129.9; 129.5,128.2,127.7,127.3,126.1; 125.3,124.1,123.2,122.0,121.3; 117.4,115.9,114.7,114.3; 114.0,112.9,72.8,69.3; MS (ESI, m/z): 505.2 [M+ H] +.
Benzyl-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound h):
Brown dope, yield 42%; IR (KBr, cm -1): n max3065,3030,2926,2870,1616,1595,1489,1450,1238,1016,962,748,698; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.68 ~ 7.64 (m, 1H, tiophene-5-H), 7.62 ~ 7.58 (m, 1H, Ar (OCH 2)-6-H), 7.47 ~ 7.26 (m, 11H, Ar-H, tiophene-CH=, Ar (OCH 2)-CH=, Ar (F)-4,5,6-H, Ar (OCH 2)-4-H), 7.20 ~ 6.98 (m, 6H, tiophene-3,4-H, tiophene-C=CH, Ar (OCH 2)-C=CH, Ar (OCH 2)-5-H, Ar (F)-2-H), 6.73 ~ 6.70 (d, j=16.0 Hz, 1H, Ar (OCH 2)-3-H), 5.24 ~ 5.23 (d, j=6.3 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer), 5.18 (s, 2H, CH 2); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 156.3,153.4,141.9,141.4,138.4; 132.1,130.5,130.1,129.8,129.3; 128.9,128.4,128.1,127.8,127.5; 127.2,127.0,125.9,125.7,123.2; 122.2,121.7,121.3,117.6,116.2; 114.3,114.1,112.8,76.4,69.3; MS (ESI, m/z): 470.2 [M+ H] +.
4-nitro-benzyl-1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound i):
Brown dope, yield 31%; IR (KBr, cm -1): n max2859,1603,1508,1344,1250,1173,1063,1015,968,735,696; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 8.26 ~ 8.25 (d, j=6.3 Hz, 2H, Ar (NO 2)-3,5-H), 7.73 ~ 7.71 (d, j=6.3 Hz, 2H, Ar (NO 2)-2,6-H), 7.67 ~ 7.55 (m, 3H, furan-5-H, Ar (OCH 2)-2,6-H), 7.49 (s, 2H, Ar-2,6-H), 7.41 ~ 7.16 (m, 5H, Ar-3,4,5-H, Ar (OCH 2)-CH=, furan-CH=), 7.13 ~ 7.02 (m, 3H, Ar (OCH 2)-3,5-H, furan-3-H), 6.87 ~ 6.78 (m, 1H, furan-4-H), 6.68 ~ 6.52 (m, 2H, Ar (OCH 2)-C=CH, furan-C=CH), 5.39 (s, 2H, CH 2), 5.19 ~ 5.17 (d, j=10.3 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 159.9,154.2,152.6,147.5,146.4,143.5,137.3,137.1; 131.7,129.2,129.0,128.5,127.9,127.6,123.5,121.9; 119.8,115.2,114.7,112.0,111.0,74.8,69.7; MS (ESI, m/z): 481.3 [M+ H] +.
CMP-1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound j):
Light yellow crystal, yield 39%, 99 ~ 101 ° of C of m.p.; IR (KBr, cm -1): n max3032,2932,1603,1508,1456,1385,1246,1015,986,745; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 8.48 (s, 1H, pyridine-6-H), 7.93 ~ 7.91 (d, j=8.0 Hz, 1H, pyridine-4-H), 7.66 ~ 7.55 (m, 3H, furan-5-H, Ar (OCH 2)-2,6-H), 7.50 ~ 7.34 (m, 6H, ArH, pyridine-3-H), 7.26 ~ 7.02 (m, 5H, Ar (OCH 2)-CH=, furan-CH=, furan-3-H, Ar (OCH 2)-3,5-H), 6.86 ~ 6.78 (m, 1H, furan-4-H), 6.66 ~ 6.52 (m, 2H, Ar (OCH 2)-C=CH, furan-C=CH), 5.27 (s, 2H, CH 2), 5.17 (s, 2H, CH 2); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 159.9,154.1,152.6,149.6,143.4; 139.3,137.3,137.0,134.0,133.3; 129.1,128.9,128.5,127.9,127.6; 124.0,121.8,119.8,115.2; 114.7,114.6,112.7,112.2; 112.0,111.0,72.7,69.7; MS (ESI, m/z): 471.3 [M+ H] +.
CMP-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound k):
Brown dope, yield 52%; IR (KBr, cm -1): n max2928,1603,1591,1508,1458,1383,1246,1175,1105,1016,964,824,781,704; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 8.48 (s, 1H, pyridine-6-H), 7.91 ~ 7.89 (d, j=8.0 Hz, 1H, pyridine-4-H), 7.59 ~ 7.57 (d, j=9.2 Hz, 2H, Ar (OCH 2)-2,6-H), 7.45 ~ 7.22 (m, 9H, tiophene-5-H, Ar (F)-4,5,6-H, pyridine-3-H, Ar (OCH 2)-CH=, tiophene-CH=, Ar (OCH 2)-C=CH, tiophene-C=CH), 7.11 ~ 7.04 (m, 4H, tiophene-3,4-H, Ar (OCH 2)-3,5-H), 6.75 ~ 6.71 (d, j=16.0 Hz, 1H, Ar (F)-2-H), 5.27 (s, 2H, CH 2), 5.19 (s, 2H, CH 2); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 159.5,154.2,150.4,149.6,141.8; 140.2,139.3,137.1,133.4,130.4; 129.4,129.0,128.2,128.0,127.5; 126.0,124.1,123.2,121.1; 115.3,114.8,114.6,114.5; 114.2,114.0,72.8,68.8; MS (ESI, m/z): 505.2 [M+ H] +.
4-nitro-benzyl-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound l):
Yellow dope, yield 38%; IR (KBr, cm -1): n max1605,1593,1508,1450,1344,1260,1240,1175,1072,1016,960,856,818,689; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 8.31 ~ 8.25 (m, 1H, Ar (NO 2)-5-H), 7.74 ~ 7.71 (t, j=7.7 Hz, 1H, Ar (NO 2)-3-H), 7.57 ~ 7.52 (m, 5H, tiophene-5-H, Ar (NO 2)-2,6-H, Ar (OCH 2)-2,6-H), 7.47 ~ 7.41 (m, 2H, tiophene-CH=, Ar (OCH 2)-CH=), 7.33 ~ 7.32 (d, j=4.6 Hz, 2H, Ar (F)-5,6-H), 7.28 ~ 7.04 (m, 7H, tiophene-3,4-H, Ar (F)-4-H, Ar (OCH 2)-3,5-H, tiophene-C=CH, Ar (OCH 2)-C=CH), 6.89 ~ 6.85 (m, 1H, Ar (F)-2-H), 5.40,5.32 (s, 2H, CH 2, e-oxime isomer+ z-oxime isomer), 5.20 (s, 2H, CH 2); 13c NMR (125 MHz, CD 3cOCD 3) δ: 159.6,154.3,147.5,146.4,141.8; 137.2,130.5,129.4,129.0,128.6; 128.5,128.0,127.6,126.1,124.2; 123.5,123.2,121.1,115.2; 115.1,114.8,114.6,114.5; 114.2,114.0,74.8,68.8; MS (ESI, m/z): 515.3 [M+ H] +.
Benzyl-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound m):
Yellow oil, yield 38%; IR (KBr, cm -1): n max3032,2920,1605,1558,1508,1458,1364,1231,1175,1015,964,698; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.64 ~ 7.62 (d, j=9.2 Hz, 2H, Ar (OCH 2)-2,6-H), 7.54 ~ 7.43 (m, 7H, tiophene-5-H, Ar-H, Ar (F)-5-H), 7.40 ~ 7.25 (m, 6H, tiophene-CH=, Ar (OCH 2)-CH=, Ar (F)-4,6-H, tiophene-3,4-H), 7.19 ~ 7.11 (m, 4H, tiophene-C=CH, Ar (OCH 2)-C=CH, Ar (OCH 2)-3,5-H), 6.85 ~ 6.82 (d, j=16.0 Hz, 1H, Ar (F)-2-H), 5.33 (s, 2H, CH 2), 5.25 (s, 2H, CH 2); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 159.5,153.4,142.0,138.4,136.7,130.4,129.5,128.9; 128.4,128.1,128.0,127.8,127.1,125.9,123.2,121.6; 115.2,115.0,114.6,114.5,114.2,114.0,76.4,68.8; MS (ESI, m/z): 470.3 [M+ H] +.
Chloro-benzyl-the 1-[2-of 2,4-bis-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound n):
Pale yellow powder, yield 50%, 100 ~ 103 ° of C of m.p.; IR (KBr, cm -1): n max3030,2916,2864,1636,1599,1560,1487,1452,1244,1107,1072,1045,959,935,731,691; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.69 ~ 7.50 (m, 7H, Ar (Cl)-3,5,6-H, furan-5-H, Ar (OCH 2)-6-H, Ar-2,6-H), 7.45 ~ 7.31 (m, 5H, Ar-3,4,5-H, Ar (OCH 2)-CH=, furan-CH=), 7.25 ~ 7.22 (d, j=16.6 Hz, 1H, Ar (OCH 2)-4-H), 7.18 ~ 7.14 (m, 1H, furan-C=CH), 7.10 ~ 6.98 (m, 3H, Ar (OCH 2)-C=CH, furan-3-H, Ar (OCH 2)-5-H), 6.62 ~ 6.53 (m, 2H, Ar (OCH 2)-3-H, furan-4-H), 5.32 ~ 5.29 (d, j=13.2 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer), 5.23 ~ 5.20 (d, j=13.2 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 156.6,154.3,152.2,144.3,137.4; 135.0,133.8,132.7,131.4,131.1; 129.8,129.5,128.9,128.6,127.9; 127.5,127.3,125.5,124.6; 121.6,121.1,117.3,114.5; 112.8,112.1,72.7,70.1; MS (ESI, m/z): 504.2 [M+ H] +.
Fluoro-benzyl-the 1-[2-of 3-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether (compound o):
Brown dope, yield 42%; IR (KBr, cm -1): n max1622,1595,1558,1489,1450,1246,1015,968,883,746,696; 1h NMR (500 MHz, CD 3cOCD 3, ppm) δ: 7.79 ~ 7.71 (m, 2H, furan-5-H, Ar (OCH 2)-6-H), 7.65 ~ 7.55 (m, 4H, Ar-2,6-H, Ar (OCH 2)-CH=, furan-CH=), 7.45 ~ 7.29 (m, 7H, Ar-3,4,5-H, Ar (F)-4,5,6-H, Ar (OCH 2)-4-H), 7.17 ~ 7.06 (m, 4H, Ar (OCH 2)-C=CH, furan-C=CH, Ar (OCH 2)-5-H, furan-3-H), 7.00 ~ 6.97 (d, j=16.0 Hz, 1H, Ar (F)-2-H), 6.61 ~ 6.53 (m, 2H, Ar (OCH 2)-3-H, furan-4-H), 5.36 (s, 2H, CH 2), 5.18 ~ 5.17 (d, j=6.3 Hz, 2H, CH 2, e-oxime isomer+ z-oxime isomer); 13c NMR (125 MHz, CD 3cOCD 3, ppm) δ: 157.0,154.4,152.7,144.1,143.4,137.2,134.2,130.5,130.3; 128.7,128.0,127.5,125.5,123.7,122.0,121.3,120.5; 117.6,114.6,114.4,112.9,112.1,111.0,75.5,70.2; MS (ESI, m/z): 454.3 [M+ H] +.
Embodiment six, the insecticidal activity testing method of compound to small cabbage moth and aphid
Topical application: be placed in culture dish with the examination worm that writing brush is chosen neat and consistent in the length of time for subsequent use.Carry out drop processing by trying worm in culture dish by head, lepidopterous larvae drop on polypide pronotum, every drop medicament 0.5-1 μl; Aphid drop is in polypide belly, every drop medicament 0.02-0.1 μl.Examination worm after drop is transferred to respectively under normal condition and is raised.Every processing 4 times repeats, and often repeats to try worm 10-20 head, and establishes not containing the processing of the corresponding organic solvent of medicament in contrast.
Dip method: target insect is soaked after into the liquid 5-10 s, draw unnecessary liquid with worry paper, examination worm is transferred under normal condition and is raised.Every processing 4 times repeats, and often repeats to soak worm 10-20 head, and establishes not containing the processing of the corresponding organic solvent of medicament in contrast.
Immersion method continuously: the healthy and strong plant of select tape root, root is carefully cleaned, dried; Plant root is inserted and is equipped with in the beaker of liquid, give normal illumination and culture condition, ensure plant root normal growth.The plant that continues to process after 24h is taken out from liquid, cut the part that base of the plant do not contact medicament and be placed in culture dish, moisturizing is for subsequent use.Every processing 4 times repeats, and often repeats to connect examination worm 10-20 head, and establishes not containing the processing of the corresponding organic solvent of medicament in contrast.
After processing, 24h investigation examination worm death condition, records total borer population and dead borer population.According to enquiry data, calculate mortality ratio and corrected mortality.The results are shown in table 2:
The anti-TMV activity of embodiment seven, compound
Live body therapeutic action: select the Nicotiana glutinosa that growing way is consistent, TMV crude extract is diluted to suitable concentration with phosphoric acid buffer, with the artificial frictional inoculation of writing brush on the of the right age blade sprinkled with silicon carbide (full leaf virus inoculation, every blade is manually smeared virus once gently, the left and right half leaf dynamics of smearing is accomplished evenly as far as possible), after inoculation, rinse with clear water. after blade is dry (after 1 h), spread compound solution at Zuo Banye, the solvent that right half leaf spreads matched doses compares.
Live body provide protection: select the Nicotiana glutinosa that growing way is consistent; spread compound solution at Zuo Banye; the solvent that right half leaf spreads matched doses compares; and moisturizing is cultivated in illumination box; control temperature (23 ± 1) DEG C, illumination 10000 Lux, are diluted to suitable concentration with phosphoric acid buffer by TMV virus crude extract after 12 h;, on the of the right age blade sprinkled with silicon carbide, after inoculation, rinse with clear water with the artificial frictional inoculation of writing brush.
Live body passivation: select the Nicotiana glutinosa that growing way is consistent, TMV is diluted to 6 × 10 with phosphoric acid buffer -3mg/mL, by compound and isopyknic viral juice mixing passivation 30 min, with the artificial frictional inoculation of writing brush, in left half leaf of the of the right age Nicotiana glutinosa sprinkled with silicon carbide, the solvent of matched doses mixes with viral juice by planting in right half leaf of the of the right age Nicotiana glutinosa sprinkled with silicon carbide; After inoculation, all rinse with clear water.
All in illumination box, moisturizing is cultivated subsequently, controls temperature (23 ± 1) DEG C, and illumination 10000 Lux observe and record the number that produces withered spot after 3 ~ 4 d.Every chemicals treatment is established 3 strains, 3 ~ 4 leaves of every strain.Every medicament carries out 3 repetitions as stated above.
The processing of experimental result: when presenting obvious withered spot on half leaf of blank, just can investigate after test 3 ~ 4 d, record respectively the withered spot number of left and right half leaf of every leaf, be calculated as follows out the inhibiting rate of test compound to plant virus, be i.e. relative effect.
Y=(C-A)/C×100%
(C is control group (right half leaf) withered spot number, and A is compound treatment group (Zuo Banye) withered spot number (unit: individual 1).Each processing be with oneself second half in contrast, then the processing that one group of commodity Ningnanmycin is set is as a comparison.)
The anti-TMV activity data of target compound is shown in table 3
table 3anti-TMV active testing result when concentration is 500 mg/L
Numbering Therapeutic action (%) Provide protection (%) Passivation (%)
A 39.31 60.69 94.43
B 42.67 53.29 95.51
C 51.35 62.18 85.38
D 35.00 57.19 92.55
E 49.58 58.42 95.03
F 38.14 54.25 85.46
G 55.36 59.30 89.46
H 56.36 63.76 90.48
I 52.07 54.54 91.50
J 58.28 66.86 78.47
K 61.70 63.94 95.80
L 61.92 61.55 87.78
M 50.99 56.33 85.90
N 47.94 62.36 88.19
O 63.46 64.36 84.00
Ningnanmycin 64.71 76.09 96.54
Wherein, therapeutic action aspect: compound g, h, j, k, lwith oinhibiting rate be all greater than 55%, suitable with the effect that contrasts medicine Ningnanmycin (inhibiting rate is 64.71%); Provide protection aspect: compound a, c, h, j, k, lwith ninhibiting rate be all greater than 60%, slightly lower than Ningnanmycin (76.09%); Passivation aspect: compound a~ gwith minhibiting rate be all greater than 85%, suitable with the effect of Ningnanmycin (96.54%).
The embodiment of the present invention is aided with explanation technical scheme of the present invention, but the content of embodiment is not limited to this.

Claims (7)

1. containing Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound of heterocycle, it is characterized by and there is general formula ( 1) compound:
In formula, as the substituting group on phenyl ring, R 1o can be at ortho position or contraposition; R 1the benzyl replacing for benzyl or containing one or more halogen atoms, itrile group, nitryl group;
R 2for phenyl, the phenyl replacing containing one or more halogen atoms, itrile group, nitro, oh group; Pyridine ring, replaces containing one or more halogen atoms, itrile group, nitryl group;
X is nitrogen, oxygen, sulfur heteroatom;
General formula be ( 1) compound small cabbage moth, aphid are had to certain insecticidal activity, there is good anti-TMV activity simultaneously.
2. compound according to claim 1, wherein said heterocyclic group is thiphene ring, furan nucleus, pyrrole ring; Described halogen atom fluorine atom, chlorine atom, bromine atoms or iodine atom.
3. compound according to claim 1, is characterized by and be selected from following particular compound:
Compound a: the chloro-benzyl-1-[2-of 2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound b: the chloro-benzyl-1-[2-of 2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound c: the chloro-benzyl-1-[2-of 2,4-bis-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound d: 4-nitro-benzyl-1-[2-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound e: the chloro-benzyl-1-[2-of 2,4-bis-(benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound f: 4-methoxyl group-benzyl-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound g: CMP-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound h: benzyl-1-[2-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether; ;
Compound i: 4-nitro-benzyl-1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound j: CMP-1-[4-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound k: CMP-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound l: 4-nitro-benzyl-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound m: benzyl-1-[4-(3-fluorine benzyloxy) phenyl]-5-(2-thiophene)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound n: the chloro-benzyl-1-[2-of 2,4-bis-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether;
Compound o: the fluoro-benzyl-1-[2-of 3-(benzyloxy) phenyl]-5-(2-furans)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether.
As described in one of claim 1-3 compound ( 1) preparation method, it is characterized in that taking monohydroxy replace phenyl aldehyde and acetone as initial feed, synthesis of hydroxy phenyl methylene acetone; With the formaldehyde reaction containing heterocyclic substituted, synthetic 1-aromatic ring-5-heterocyclic substituted-Isosorbide-5-Nitrae-pentadiene-3-ketone compounds; Its 1-aromatic ring phenolic hydroxyl group is carried out to etherificate; Then oximate, etherificate again, synthetic Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound containing heterocycle ( 1), synthetic route is as follows:
。
5. the preparation method of a kind of Isosorbide-5-Nitrae-pentadiene-3-ketoxime ether compound containing heterocycle according to claim 4 is characterized in that processing step and processing condition are:
The first step, the preparation of 4-(adjacent or to) hydroxy phenyl-3-butene-2-one
The phenyl aldehyde that monohydroxy is replaced joins in acetone, stir, drip 5% aqueous sodium hydroxide solution under ice bath, reaction solution becomes burgundy clear liquid from faint yellow clear liquid, after reaction finishes, under condition of ice bath, slowly drip dilute hydrochloric acid solution, have faint yellow solid to produce, filter, washing, dry, use acetone/water recrystallization, obtain faint yellow solid;
The ratio of amount of substance, monosubstituted hydroxy aldehyde: acetone: sodium hydroxide=1:30:2.2～2.5
Temperature of reaction: 20～24 DEG C
Reaction times: 10～30 h
This step is applicable to the synthetic of all above-mentioned 4-(adjacent or to) hydroxy phenyl-3-butene-2-one;
Second step, the preparation of 1-(adjacent or to) hydroxy phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone
By 4-(adjacent or to) hydroxy phenyl-3-butene-2-one and heterocyclic aldehydes, be dissolved in dehydrated alcohol, stir, under condition of ice bath, be added dropwise to 5% aqueous sodium hydroxide solution, reaction solution becomes burgundy clear liquid from faint yellow clear liquid;
After question response is complete, under condition of ice bath, slowly drip dilute hydrochloric acid solution, have faint yellow solid to produce, filter, wash, dry, with dehydrated alcohol/water recrystallization, obtain light yellow crystal;
The ratio of amount of substance, 4-(adjacent or to) hydroxy phenyl-3-butene-2-one: sodium hydroxide: heterocyclic aldehydes=1.1:2.5:1 temperature of reaction: 20～25 DEG C
Reaction times: 15～20 h
This step is applicable to the synthetic of all above-mentioned 1-(adjacent or to) hydroxy phenyl-5-heterocyclic radical-Isosorbide-5-Nitrae-pentadiene-3-ketone;
The 3rd step, the preparation of 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone
1-(adjacent or to) hydroxy phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone, Anhydrous potassium carbonate, potassiumiodide are dissolved in acetone, stir, drip the acetone soln that contains (replacement) benzyl chlorine, reflux;
After reaction finishes, be chilled to room temperature, filter, revolve and steam except desolventizing, ethanol or acetone recrystallization, obtain yellow crystals;
The ratio of amount of substance, 1-(adjacent or to) hydroxy phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone: (replacement) benzyl chlorine: Anhydrous potassium carbonate: potassiumiodide=1:1.2:1.5:0.3 temperature of reaction: 50～60 DEG C
Reaction times: 4-8 h
This step is applicable to the synthetic of all above-mentioned 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone;
The 4th step, the preparation of 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime
1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone, oxammonium hydrochloride are added in dehydrated alcohol, stir, drip pyridine; Under room temperature, stir, solution becomes yellow clear liquid from suspension, reacts completely, rotary evaporation is except desolventizing, add methylene dichloride, drip 5% dilute hydrochloric acid (volume ratio), regulate pH value to be about 5 ~ 6, washing, anhydrous sodium sulfate drying, filters precipitation, obtain yellow viscous fluid, column chromatography for separation obtains pale yellow powder;
The ratio of amount of substance, 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketone: oxammonium hydrochloride: pyridine=1:2.5:30
Temperature of reaction: 20～25 DEG C
Reaction times: 40～50 h
This step is applicable to the synthetic of all above-mentioned 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime;
The 5th step, target compound substituted-phenyl or heterocyclic radical-1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3
Synthesizing of ketoxime ether
1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime, Anhydrous potassium carbonate are dissolved in dry acetonitrile, stir, drip and contain the anhydrous acetonitrile that replaces benzyl chlorine, reflux;
After reaction finishes, be chilled to room temperature,
Filter, concentrated filtrate, obtains brown oil, adds methylene dichloride, and with saturated common salt washing, anhydrous sodium sulfate drying, filters, precipitation, and column chromatography for separation obtains target compound;
The ratio of amount of substance, 1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3-ketoxime: salt of wormwood: benzyl chlorine=1:2:1.2
Temperature of reaction: 75～85 DEG C
Reaction times: 2-6 h
This step is applicable to the synthetic of all above-mentioned substituted-phenyls or heterocyclic radical-1-(substituted benzyloxy) phenyl-5-(2-heterocyclic radical)-Isosorbide-5-Nitrae-pentadiene-3 ketoxime ether.
6. according to the application of the compound described in claim 1-3 any one, it is characterized in that as sterilant and antiviral agent.
7. purposes according to claim 5, is characterized in that as control small cabbage moth, the medicine of aphid and the medicine of resisting tobacco mosaic virus (TMV).
CN201410154762.7A 2014-04-17 2014-04-17 Heterocyclic 1,4-pentadiene-3-ketoxime compound as well as preparation method and application thereof Pending CN103923061A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106749046A (en) * 2016-12-08 2017-05-31 贵州大学 The ketoxime ether derivative of 1,4 pentadiene 3 of one kind containing 4 (3H) quinazolinones and preparation method thereof
CN107056687A (en) * 2016-11-23 2017-08-18 贵州大学 The ketoxime ester compound of 1,4 pentadiene 3, Preparation method and use containing pyridine groups

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101973934A (en) * 2010-09-06 2011-02-16 贵州大学 1,5-disubstituted aryl-1,4-pentadiene-3-ketoxime ether compound and preparation method thereof and insecticidal activity application
CN103554080A (en) * 2013-11-13 2014-02-05 贵州大学 1,4-pentadiene-3-ketoxime ester compounds containing heterocyclic groups as well as preparation method and application thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101973934A (en) * 2010-09-06 2011-02-16 贵州大学 1,5-disubstituted aryl-1,4-pentadiene-3-ketoxime ether compound and preparation method thereof and insecticidal activity application
CN103554080A (en) * 2013-11-13 2014-02-05 贵州大学 1,4-pentadiene-3-ketoxime ester compounds containing heterocyclic groups as well as preparation method and application thereof

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107056687A (en) * 2016-11-23 2017-08-18 贵州大学 The ketoxime ester compound of 1,4 pentadiene 3, Preparation method and use containing pyridine groups
CN107056687B (en) * 2016-11-23 2020-06-30 贵州大学 Pyridine group-containing 1, 4-pentadiene-3-ketoxime ester compound, preparation method and application
CN106749046A (en) * 2016-12-08 2017-05-31 贵州大学 The ketoxime ether derivative of 1,4 pentadiene 3 of one kind containing 4 (3H) quinazolinones and preparation method thereof
CN106749046B (en) * 2016-12-08 2019-08-09 贵州大学 One kind containing the 1,4- pentadiene -3- ketoxime ether derivative and preparation method thereof of 4 (3H)-quinazolinones

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