CN104003924A - N-substituent-3-[3-(substituted phenyl)-2-allyl-1- ketone]-4-hydroxypyrroline-2-ketone compound as well as preparation method and application thereof - Google Patents

N-substituent-3-[3-(substituted phenyl)-2-allyl-1- ketone]-4-hydroxypyrroline-2-ketone compound as well as preparation method and application thereof Download PDF

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CN104003924A
CN104003924A CN201410230403.5A CN201410230403A CN104003924A CN 104003924 A CN104003924 A CN 104003924A CN 201410230403 A CN201410230403 A CN 201410230403A CN 104003924 A CN104003924 A CN 104003924A
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ketone
pyrroline
hydroxyl
alkene
phenyl
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CN104003924B (en
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杨松
冉义江
薛伟
吴志兵
陈玲
张东阳
丁永正
刘斌
胡德禹
向红梅
张腾腾
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Guizhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/38—2-Pyrrolones
    • 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
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings

Abstract

The invention discloses an N-substituent-3-[3-(substituted phenyl)-2-allyl-1- ketone]-4-hydroxypyrroline-2-ketone compound as well as a preparation method and application thereof, belonging to the technical field of organic synthesis and pesticides. The compound has a general structural formula (I). The N-substituent-3-[3-(substituent phenyl)-2-allyl-1- ketone]-4-hydroxypyrroline-2-ketone compound is synthesized from substituted phenylamine, ethyl chloroacetate, ethyl acetoacetate and substituted benzaldehyde. The compound has good tobacco mosaic virus resistant living body treatment activity and can be used for preparing plant virus resistant pesticides.

Description

N-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one compounds and preparation method and application
Technical field
The present invention relates to have the compound of Antiphytoviral and plant epiphyte, specifically n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] preparation method and the application of-4-hydroxyl pyrroline-2-one compounds.
Background technology
Pyrrolines is the important heterogeneous ring compound of a class, has sterilization, weeding, desinsection, except mite and agricultural chemicals and the medicinal activity such as antitumor, anti-infective.Isosorbide-5-Nitrae-pentadiene-3-ketone compounds is a kind of curcumin analogue, has agricultural chemicals and the medicinal activities such as plant epiphyte resisting, Antiphytoviral, anticancer, anti-inflammatory, anti-oxidant, anti-HIV.Therefore, take pyrrolines introduces Isosorbide-5-Nitrae-pentadiene-3-ketone structure as natural skeleton and carries out further exploitation and have very wide prospect.
1993, (Addor, the R. W. such as Addor; Donovan, S. F.; DIehl, R. E. n-Acylated A rylpyrroles Useful as In sectIcIdal A gents [P]. uS 5328928., 1993.) report and synthesized compound n-acidylate pyrrole derivatives.By biological activity test, show that this compounds has good pesticide and miticide actility, this compounds is 10 in concentration μduring g/mL to southern mythimna separata ( spodop terae IdanIa), Heliothis virescens ( helIothIs vIrescens) third-instar larvae, western potato leaf hopper ( empoasca abrupta) and the tetranychid of organophosphorus resistant strain ( t. urtIcae) lethality rate all reach 100%, to cucumber 11 asterophyllite first ( dIabrotIc undecImp unctata howawdI) and blattaria ( blattellager manIca) also have good inhibition active.
2007, Zhu have congruence (Zhu Youquan, department learns triumphant, Zou little Mao, Liu Bin, Yang Huazheng. novel 3-hydroxy methylene tetramethyleneimine-2, the synthetic and weeding activity research [J] of 4-derovatives. organic chemistry., 2007, 27 (3): 355-390.).Reported novel 3-hydroxy methylene tetramethyleneimine-2,4-dione compounds, take sulphur humulone as contrast medicament, by rape Plating and the little agar diffusion method of barnyard grass, this compounds is carried out to weeding activity test, and test result shows, this compounds has good weeding activity.
2011, Zhou Bing etc. (Zhou Bing, Yan little Hong, Peng Feng, Guo Nianmei, Zhong Juan, Yin Shuaiwen. the bacteriostatic activity of alternaria alternata metabolite [J]. university Of Agriculture and Forestry In Fujian's journal (natural science edition)., 201140 (4): 416-420.) having reported that alternaric bacteria methyl aceto acetate phase metabolite has certain restraining effect to gibberella saubinetii, rice blast fungus, Sclerotinia sclerotiorum, tobacco ash arrhizus bacteria and dothiorella gregaria bacterium 5 kind of plant pathogenic fungies, is 800 in concentration μduring g/mL, the inhibiting rate of 5 kinds of fungies is respectively to 38.11 %, 76.35%, 47.81%, 60.24%, 57.24%.Contrast medicament derosal is 800 in concentration μduring g/mL, the inhibiting rate of 5 kinds of fungies is respectively to 100%, 81.16%, 78.96%, 72.76%, 94.82%.It is active that result shows that alternaric bacteria methyl aceto acetate phase metabolite has good inhibition to rice blast fungus.
2003, (ReksohadIprodjo, the M. S. such as ReksohadIprodjo; TImmerman, H.; SardjIman, S. S. DerIvatIves of benzylIdene cyclohexanone, benzylIdene cyclopentanone, and benzylIdene acetone, and therapeutIc uses thereof [P]. uS 0092772A., 2003) synthesized serial substituted-phenyl-Isosorbide-5-Nitrae-pentadiene-3-ketone and cyclopentanone, pimelinketone analogue, and under 10,20,40 and 80 mg/kg dosage, treat white mouse claw edema, to judge the antiphlogistic activity of each compound.Result of study shows, this compounds has good activity, ED 50value minimum is 20 mg/kg, compound to staphylococcus aureus ( staphyloccocus aureus Rosenbach), streptococcus pneumoniae ( streptococcus pneumonIae), withered grass brood cell ( bacIllus subtIlIs), Candida albicans ( canIdIa albIcans) etc. there is good restraining effect, wherein compound is 0.05 to the minimum inhibition concentration of staphylococcus aureus μmol/L.
2004, (Youssef, the K. M. such as Yousse; El-Sherbeny; El-ShafIle, M. A. SynthesIs of curcumIn analogues as potentIal antIoxIdant, cancer hemopreventIve agents [J]. arch. Pharm. Med. Chem., 2004, 337:42-54.) reported 7 serial curcumin derivates, find that compound shows the activity of trinitro-free radical between good removing phenylbenzene, inhibiting rate is 91.24% ~ 99.85%.In addition, compound is the safest to periphery multinuclear neutrophilic granulocyte, and surviving rate reaches 91%.
2006, (RamalIngan, the C. such as RamalIngan; Park, Y. T.; KabIlan, S. SynthesIs, stereochemIstry and antImIcrobIal evaluatIon of substItuted pIperIdIn-4-one oxIme ethers [J]. eur. J. Med. Chem., 2006, 41 (6): 683-696.) reported compound 2,6-diphenyl-piperidine-4-ketoxime ether compound, has carried out the test of antibacterial, antimicrobial and anti-mycotic activity to this compounds, test result shows, compound to Bacillus subtilus ( bacIllus subtIlIs) to have shown good inhibition active, its minimum inhibition concentration (MIC) and control drug Streptomycin sulphate ( streptomycIn) approach.Compound to flavus ( aspergIllus flavus) and candidiasis-51 ( candIda-51) show potential inhibition activity.According to MIC data, the activity of compound and control drug amphotericin ( amphoterIcIn) approach.
From background technology, pyrrolines has good sterilization, weeding, desinsection, removes mite activity; The sterilization of Isosorbide-5-Nitrae-pentadiene-3-ketone compounds, the biological activity such as anti-oxidant.But about take natural pyrroline as basic framework, the compound of introducing Isosorbide-5-Nitrae-pentadiene-3-ketone structure there is no at present people and reported, and also less about the research report of this compounds activity of resisting tobacco mosaic virus both at home and abroad.
Summary of the invention
The object of the invention is to design and synthesized the new pyrrole quinoline compounds containing Isosorbide-5-Nitrae-pentadiene-3-ketone structure of a series of novel structures.This compounds be take natural pyrroline as basic framework, introduces Isosorbide-5-Nitrae-pentadiene-3-ketone structure on three, and this series compound has been carried out to synthetic method and the test of Antiphytoviral live body treatment prolection.
The present invention, n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one compounds, its general structure is as follows:
( I)
R wherein 1be 2,3-dichloro, 2-methoxyl group, 2,3-dimethoxy, the fluoro-4-bromine of 2-, 3-nitro, 4-methyl, 4-bromine, 2-fluorine, 3-bromine, the fluoro-6-chlorine of 2-, 4-fluorine, 3,4-dichloro, 2,6-dichloro, 2-chlorine, 4-chlorine, hydrogen;
R 2for 4-methyl, 3,4-dimethyl.
Synthetic compound is as follows:
I1 N-p-methylphenyl-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I2 N-p-methylphenyl-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I3 N-p-methylphenyl-3-[3-(2,3-Dimethoxyphenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I4 N-p-methylphenyl-3-[3-(the fluoro-4-bromophenyl of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I5 N-p-methylphenyl-3-[3-(3-nitrophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I6 N-p-methylphenyl-3-[3-(4-aminomethyl phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I7 N-p-methylphenyl-3-[3-(4-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I8 N-p-methylphenyl-3-[3-(2-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I9 N-p-methylphenyl-3-[3-(3-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I10 N-p-methylphenyl-3-[3-(the fluoro-6-chloro-phenyl-of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I11 N-p-methylphenyl-3-[3-(4-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I12 N-p-methylphenyl-3-[3-(3,4-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I13 N-p-methylphenyl-3-[3-(2-6-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I14 N-p-methylphenyl-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I15 N-p-methylphenyl-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I16 N-(3,4-3,5-dimethylphenyl)-3-[3-(4-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I17 N-(3,4-3,5-dimethylphenyl)-3-[3-(4-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I18 N-(3,4-3,5-dimethylphenyl)-3-[3-(2-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I19 N-(3,4-3,5-dimethylphenyl)-3-[3-(3,4-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I20 N-(3,4-3,5-dimethylphenyl)-3-[3-(3-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I21 N-(3,4-3,5-dimethylphenyl)-3-[3-(the fluoro-4-bromophenyl of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I22 N-(3,4-3,5-dimethylphenyl)-3-(3-phenyl-2-alkene-1-ketone)-4-hydroxyl pyrroline-2 ketone
I23 N-(3,4-3,5-dimethylphenyl)-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I24 N-(3,4-3,5-dimethylphenyl)-3-[3-(3-nitrophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I25 N-(3,4-3,5-dimethylphenyl)-3-[3-(the fluoro-6-chloro-phenyl-of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I26 N-(3,4-3,5-dimethylphenyl)-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I27 N-(3,4-3,5-dimethylphenyl)-3-[3-(4-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I28 N-(3,4-3,5-dimethylphenyl)-3-[3-(2,6-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I29 N-(3,4-3,5-dimethylphenyl)-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
I30 N-(3,4-3,5-dimethylphenyl)-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
The application of compound of the present invention is to prepare the application in plant epiphyte resisting and plant virus medicine.
The application of above-mentioned indication in preparing plant epiphyte resisting and plant virus medicine refers to medicine and the medicament for the preparation of resisting tobacco mosaic virus, fusarium graminearum, capsicum wilt bacterium, Valsa mali.
Of the present invention n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] synthetic method of-4-hydroxyl pyrroline-2-one compounds is with substituted aniline, ethyl chloroacetate, methyl aceto acetate, substituted benzaldehyde is raw material, take ethanol, dimethylbenzene, methyl alcohol as solvent is substituted, closed loop, aldol reaction be synthetic, its synthetic route is:
。
The present invention n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] synthesis step and the processing condition of-4-hydroxyl pyrroline-2-one compounds are:
The first step: nthe preparation of-phenylglycine ethyl ester;
To adding substituted aniline, ethyl chloroacetate, 95% ethanol and sodium acetate in there-necked flask, mol ratio wherein: substituted aniline: ethyl chloroacetate: sodium ethylate=1:1:1-1:1.2:1, every 5mmol substituted aniline adds 95% ethanol 10 mL, reflux, TLC follows the tracks of reaction process, after reaction finishes, adds water, then with benzene, extract, combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with the white solid of dehydrated alcohol recrystallization n-phenylglycine ethyl ester;
Second step: nthe preparation of-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one.
Get substituted-phenyl glycine ethyl ester, methyl aceto acetate, dry dimethylbenzene joins in there-necked flask, at 125-130 ℃ of 24 h that reflux, mol ratio wherein: substituted-phenyl glycine ethyl ester: methyl aceto acetate=1:1-1:1.5, every 1.3 mmol substituted-phenyl glycine ethyl esters add the dry dimethylbenzene of 5 ml, TLC follows the tracks of reaction process, after raw material reaction is complete, be cooled to normal temperature, by 1.3 mmol substituted-phenyl glycine ethyl esters, be that to add concentration be 1 mol/L sodium methylate 15 mL to standard, under normal temperature, stir 48 h, TLC follows the tracks of reaction process, after reaction finishes, in system, add 20 mL water, with 20% dilute hydrochloric acid, be adjusted to pH=2-3, with 20mL dichloromethane extraction 3 times, combining extraction liquid, use saturated common salt water washing, collect organic phase and use anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product obtains solid by methylene dichloride and recrystallizing methanol n-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one;
The 3rd step: n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one:
Take n-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one, adds anhydrous methanol and 50% KOH to join in there-necked flask, every 2 mmol n-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one adds anhydrous methanol 20 mL, 50% KOH 2mL, and stirring at normal temperature 20 minutes, produces a large amount of white flosss, adds substituted benzaldehyde, wherein mol ratio: n-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one: substituted benzaldehyde=1:5; connect prolong backflow 6-8 h; TLC follows the tracks of reaction process; after reaction finishes, to system, add 10 mL water, with 20% dilute hydrochloric acid, be adjusted to pH=2-3; separate out a large amount of yellow solids; normal pressure solid collected by filtration, dry for standby, adopts column chromatography for separation to obtain target compound n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
The present invention n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one compounds is easy to synthesize, and cost is low.Design of the present invention meets the requirement of environmental friendliness and Green Chemistry; The synthetic compound of the inventive method can be used as resisting tobacco mosaic virus drug use.
By embodiment once, foregoing of the present invention is described in further detail.
Embodiment
Embodiment mono-, n-p-methylphenyl-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone]-(compound number is 4-hydroxyl pyrroline-2-one i1) preparation.
The first step: nthe preparation of-p-methylphenyl glycine ethyl ester:
In the there-necked flask of 50 mL, add para-totuidine 0.55 g (5 mmoL), ethyl chloroacetate 0.73 g (6 mmol), 95% ethanol 10 mL, 0.49 g (5 mmol) sodium acetate.Reflux 6 h, add 20 mL water after reaction finishes, then with 20 mL benzene extraction 3 times, and combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with dehydrated alcohol recrystallization, obtains white solid n-p-methylphenyl glycine ethyl ester;
Second step: nthe preparation of-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one:
Get n-p-methylphenyl glycine ethyl ester 1 g (1.3 mmol), methyl aceto acetate 0.28 g (1.9 mmol), 5 mL are dry, and dimethylbenzene joins in there-necked flask, after 125-130 ℃ of backflow 24 h, be cooled to normal temperature, add 15 mL sodium methylates (1 mol/L), under normal temperature, stir 48 h.After reaction finishes, in system, add 20 mL water, the dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction 3 times, combining extraction liquid, uses saturated common salt water washing, collect organic phase and with anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product CH 3oH:CHCl 3=3:1 (volume ratio) recrystallization obtains compound n-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one;
The 3rd step: n-p-methylphenyl-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one:
Take n-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one 500 mg (2 mmol), measure 20 mL anhydrous methanols, 2 mL 50% KOH join in there-necked flask, stirring at normal temperature 20 mIn, produce a large amount of white flosss, add 10 mmol 2, 3-dichlorobenzaldehyde, connect prolong backflow 6-8 h, TLC follows the tracks of reaction process, after reaction finishes, to system, add 10 mL water, dilute hydrochloric acid with 20% regulates pH=2-3, separate out a large amount of yellow solids, normal pressure solid collected by filtration, dry for standby, adopt column chromatography for separation (methylene dichloride: triethylamine=250:1) (volume ratio), precipitation, add water, dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction three times, combining extraction liquid, removal of solvent under reduced pressure obtains target compound n-p-methylphenyl-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
Embodiment bis-, n-p-methylphenyl-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-(compound number is 4-hydroxyl pyrroline-2-one i2) preparation.
The first step: nthe preparation of-p-methylphenyl glycine ethyl ester.
In the there-necked flask of 50 mL, add para-totuidine 0.55 g (5 mmoL), ethyl chloroacetate 0.73 g (6 mmol), 95% ethanol 10 mL, 0.49 g (5 mmol) sodium acetate.Reflux 6 h, add 20 mL water after reaction finishes, then with 20 mL benzene extraction 3 times, and combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with dehydrated alcohol recrystallization, obtains white solid n-p-methylphenyl glycine ethyl ester.
Second step: nthe preparation of-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
Get n-p-methylphenyl glycine ethyl ester 1 g (1.3 mmol), methyl aceto acetate 0.28 g (1.9 mmol), 5 mL are dry, and dimethylbenzene joins in there-necked flask, after 125-130 ℃ of backflow 24 h, be cooled to normal temperature, add 15 mL sodium methylates (1 mol/L), under normal temperature, stir 48 h.After reaction finishes, in system, add 20 mL water, the dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction 3 times, combining extraction liquid, uses saturated common salt water washing, collect organic phase and with anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product CH 3oH:CHCl 3=3:1 (volume ratio) recrystallization obtains compound n-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
The 3rd step: n-p-methylphenyl-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one.
Take n-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one 500 mg (2 mmol), measure 20 mL anhydrous methanols, 2 mL 50% KOH join in there-necked flask, stirring at normal temperature 20 mIn, produce a large amount of white flosss, add 10 mmol Benzaldehyde,2-methoxies, connect prolong backflow 6-8 h, TLC follows the tracks of reaction process, after reaction finishes, to system, add 10 mL water, dilute hydrochloric acid with 20% regulates pH=2-3, separate out a large amount of yellow solids, normal pressure solid collected by filtration, dry for standby, adopt column chromatography for separation (methylene dichloride: triethylamine=250:1) (volume ratio), precipitation, add water, dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction three times, combining extraction liquid, removal of solvent under reduced pressure obtains target compound n-p-methylphenyl-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
Embodiment tri-, n-p-methylphenyl-3-[3-(2,6-dichlorophenyl)-2-alkene-1-ketone]-(compound number is 4-hydroxyl pyrroline-2-one i13) preparation.
The first step: nthe preparation of-p-methylphenyl glycine ethyl ester.
In the there-necked flask of 50 mL, add para-totuidine 0.55 g (5 mmoL), ethyl chloroacetate 0.73 g (6 mmol), 95% ethanol 10 mL, 0.49 g (5 mmol) sodium acetate.Reflux 6 h, add 20 mL water after reaction finishes, then with 20 mL benzene extraction 3 times, and combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with dehydrated alcohol recrystallization, obtains white solid n-p-methylphenyl glycine ethyl ester.
Second step: nthe preparation of-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
Get n-p-methylphenyl glycine ethyl ester 1 g (1.3 mmol), methyl aceto acetate 0.28 g (1.9 mmol), 5 mL are dry, and dimethylbenzene joins in there-necked flask, after 125-130 ℃ of backflow 24 h, be cooled to normal temperature, add 15 mL sodium methylates (1 mol/L), under normal temperature, stir 48 h.After reaction finishes, in system, add 20 mL water, the dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction 3 times, combining extraction liquid, uses saturated common salt water washing, collect organic phase and with anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product CH 3oH:CHCl 3=3:1 (volume ratio) recrystallization obtains compound n-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
The 3rd step: n-p-methylphenyl-3-[3-(2,6-dichlorophenyl)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one.
Take n-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one 500 mg (2 mmol), measure 20 mL anhydrous methanols, 2 mL 50% KOH join in there-necked flask, stirring at normal temperature 20 mIn, produce a large amount of white flosss, add 10 mmol 2, 6-dichlorobenzaldehyde, connect prolong backflow 6-8 h, TLC follows the tracks of reaction process, after reaction finishes, to system, add 10 mL water, dilute hydrochloric acid with 20% regulates pH=2-3, separate out a large amount of yellow solids, normal pressure solid collected by filtration, dry for standby, adopt column chromatography for separation (methylene dichloride: triethylamine=250:1) (volume ratio), precipitation, add water, dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction three times, combining extraction liquid, removal of solvent under reduced pressure obtains target compound n-p-methylphenyl-3-[3-(2,6-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
Embodiment tetra-, n-p-methylphenyl-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone]-(compound number is 4-hydroxyl pyrroline-2-one i15) preparation.
The first step: nthe preparation of-p-methylphenyl glycine ethyl ester.
In the there-necked flask of 50 mL, add para-totuidine 0.55 g (5 mmoL), ethyl chloroacetate 0.73 g (6 mmol), 95% ethanol 10 mL, 0.49 g (5 mmol) sodium acetate.Reflux 6 h, add 20 mL water after reaction finishes, then with 20 mL benzene extraction 3 times, and combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with dehydrated alcohol recrystallization, obtains white solid n-p-methylphenyl glycine ethyl ester.
Second step: nthe preparation of-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
Get n-p-methylphenyl glycine ethyl ester 1 g (1.3 mmol), methyl aceto acetate 0.28 g (1.9 mmol), 5 mL are dry, and dimethylbenzene joins in there-necked flask, after 125-130 ℃ of backflow 24 h, be cooled to normal temperature, add 15 mL sodium methylates (1 mol/L), under normal temperature, stir 48 h.After reaction finishes, in system, add 20 mL water, the dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction 3 times, combining extraction liquid, uses saturated common salt water washing, collect organic phase and with anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product CH 3oH:CHCl 3=3:1 (volume ratio) recrystallization obtains compound n-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
The 3rd step: n-p-methylphenyl-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one.
Take n-p-methylphenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one 500 mg (2 mmol), measure 20 mL anhydrous methanols, 2 mL 50% KOH join in there-necked flask, stirring at normal temperature 20 mIn, produce a large amount of white flosss, add 10 mmol 2, 4-dichlorobenzaldehyde, connect prolong backflow 6-8 h, TLC follows the tracks of reaction process, after reaction finishes, to system, add 10 mL water, dilute hydrochloric acid with 20% regulates pH=2-3, separate out a large amount of yellow solids, normal pressure solid collected by filtration, dry for standby, adopt column chromatography for separation (methylene dichloride: triethylamine=250:1) (volume ratio), precipitation, add water, dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction three times, combining extraction liquid, removal of solvent under reduced pressure obtains target compound n-p-methylphenyl-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
Embodiment five, n-(3,4-3,5-dimethylphenyl)-3-[3-(4-chloro-phenyl-)-2-alkene-1-ketone]-(compound number is 4-hydroxyl pyrroline-2-one i16) preparation.
The first step: nthe preparation of-(3,4-3,5-dimethylphenyl) glycine ethyl ester.
In the there-necked flask of 50 mL, add to 3,4-xylidine, 0.63 g (5 mmoL) ethyl chloroacetate 0.735 g (6 mmol), 95% ethanol 10 mL, 0.492 g (5 mmol) sodium acetate.Reflux 6 h, add 20 mL water after reaction finishes, then with 20 mL benzene extraction 3 times, and combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with dehydrated alcohol recrystallization, obtains white solid n-(3,4-3,5-dimethylphenyl) glycine ethyl ester.
Second step: nthe preparation of-(3,4-dimethyl) phenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
Get n-(3,4-3,5-dimethylphenyl) glycine ethyl ester 1 g (1.2mmol), methyl aceto acetate 0.28 g (1.9mmol), 5 mL are dry, and dimethylbenzene joins in there-necked flask, after 125-130 ℃ of backflow 24 h, be cooled to normal temperature, add 15 mL sodium methylates (1 mol/L), under normal temperature, stir 48 h.After reaction finishes, in system, add 20 mL water, the dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction 3 times, combining extraction liquid, uses saturated common salt water washing, collect organic phase and with anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product CH 3oH:CHCl 3=3:1 (volume ratio) recrystallization obtains compound n-(3,4-dimethyl) phenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
The 3rd step: n-(3,4-3,5-dimethylphenyl)-3-[3-(4-chloro-phenyl-)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one.
Take n-(3, 4-3,5-dimethylphenyl)-3-ethanoyl-4-hydroxyl pyrroline-2-one 500 mg (1.9 mmol), measure 20 mL anhydrous methanols, 2 mL 50% KOH join in there-necked flask, stirring at normal temperature 20 mIn, produce a large amount of white flosss, add 10 mmol 4-chlorobenzaldehydes, connect prolong backflow 6-8 h, TLC follows the tracks of reaction process, after reaction finishes, to system, add 10 mL water, dilute hydrochloric acid with 20% regulates pH=2-3, separate out a large amount of yellow solids, normal pressure solid collected by filtration, dry for standby, adopt column chromatography for separation (methylene dichloride: triethylamine=250:1), precipitation, add water, dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction three times, combining extraction liquid, the target compound of removal of solvent under reduced pressure n-(3,4-3,5-dimethylphenyl)-3-[3-(4-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
Embodiment six, n-(3,4-3,5-dimethylphenyl)-3-[3-(4-bromophenyl)-2-alkene-1-ketone]-(compound number is 4-hydroxyl pyrroline-2-one i17) preparation.
The first step: nthe preparation of-(3,4-3,5-dimethylphenyl) glycine ethyl ester.
In the there-necked flask of 50 mL, add to 3,4-xylidine, 0.63 g (5 mmoL) ethyl chloroacetate 0.735 g (6 mmol), 95% ethanol 10 mL, 0.492 g (5 mmol) sodium acetate.Reflux 6 h, add 20 mL water after reaction finishes, then with 20 mL benzene extraction 3 times, and combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with dehydrated alcohol recrystallization, obtains white solid n-(3,4-3,5-dimethylphenyl) glycine ethyl ester.
Second step: nthe preparation of-(3,4-dimethyl) phenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
Get n-(3,4-3,5-dimethylphenyl) glycine ethyl ester 1 g (1.2mmol), methyl aceto acetate 0.28 g (1.9mmol), 5 mL are dry, and dimethylbenzene joins in there-necked flask, after 125-130 ℃ of backflow 24 h, be cooled to normal temperature, add 15 mL sodium methylates (1 mol/L), under normal temperature, stir 48 h.After reaction finishes, in system, add 20 mL water, the dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction 3 times, combining extraction liquid, uses saturated common salt water washing, collect organic phase and with anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product CH 3oH:CHCl 3=3:1 (volume ratio) recrystallization obtains compound n-(3,4-dimethyl) phenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
The 3rd step: n-(3,4-3,5-dimethylphenyl)-3-[3-(4-bromophenyl)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one.
Take n-(3, 4-3,5-dimethylphenyl)-3-ethanoyl-4-hydroxyl pyrroline-2-one 500 mg (1.9 mmol), measure 20 mL anhydrous methanols, 2 mL 50% KOH join in there-necked flask, stirring at normal temperature 20 mIn, produce a large amount of white flosss, add 10 mmol 4-bromobenzaldehydes, connect prolong backflow 6-8 h, TLC follows the tracks of reaction process, after reaction finishes, to system, add 10 mL water, dilute hydrochloric acid with 20% regulates pH=2-3, separate out a large amount of yellow solids, normal pressure solid collected by filtration, dry for standby, adopt column chromatography for separation (methylene dichloride: triethylamine=250:1), precipitation, add water, dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction three times, combining extraction liquid, the target compound of removal of solvent under reduced pressure n-(3,4-3,5-dimethylphenyl)-3-[3-(4-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
Embodiment seven, n-(3,4-3,5-dimethylphenyl)-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone]-(compound number is 4-hydroxyl pyrroline-2-one i29) preparation.
The first step: nthe preparation of-(3,4-3,5-dimethylphenyl) glycine ethyl ester.
In the there-necked flask of 50 mL, add to 3,4-xylidine, 0.63 g (5 mmoL) ethyl chloroacetate 0.735 g (6 mmol), 95% ethanol 10 mL, 0.492 g (5 mmol) sodium acetate.Reflux 6 h, add 20 mL water after reaction finishes, then with 20 mL benzene extraction 3 times, and combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with dehydrated alcohol recrystallization, obtains white solid n-(3,4-3,5-dimethylphenyl) glycine ethyl ester.
Second step: nthe preparation of-(3,4-dimethyl) phenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
Get n-(3,4-3,5-dimethylphenyl) glycine ethyl ester 1 g (1.2mmol), methyl aceto acetate 0.28 g (1.9mmol), 5 mL are dry, and dimethylbenzene joins in there-necked flask, after 125-130 ℃ of backflow 24 h, be cooled to normal temperature, add 15 mL sodium methylates (1 mol/L), under normal temperature, stir 48 h.After reaction finishes, in system, add 20 mL water, the dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction 3 times, combining extraction liquid, uses saturated common salt water washing, collect organic phase and with anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product CH 3oH:CHCl 3=3:1 (volume ratio) recrystallization obtains compound n-(3,4-dimethyl) phenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
The 3rd step: n-(3,4-3,5-dimethylphenyl)-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one.
Take n-(3, 4-3,5-dimethylphenyl)-3-ethanoyl-4-hydroxyl pyrroline-2-one 500 mg (1.9 mmol), measure 20 mL anhydrous methanols, 2 mL 50% KOH join in there-necked flask, stirring at normal temperature 20 mIn, produce a large amount of white flosss, add 10 mmol 2-chlorobenzaldehydes, connect prolong backflow 6-8 h, TLC follows the tracks of reaction process, after reaction finishes, to system, add 10 mL water, dilute hydrochloric acid with 20% regulates pH=2-3, separate out a large amount of yellow solids, normal pressure solid collected by filtration, dry for standby, adopt column chromatography for separation (methylene dichloride: triethylamine=250:1), precipitation, add water, dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction three times, combining extraction liquid, the target compound of removal of solvent under reduced pressure n-(3,4-3,5-dimethylphenyl)-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
Embodiment eight, n-(3,4-3,5-dimethylphenyl)-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-(compound number is 4-hydroxyl pyrroline-2-one i30) preparation.
The first step: nthe preparation of-(3,4-3,5-dimethylphenyl) glycine ethyl ester.
In the there-necked flask of 50 mL, add to 3,4-xylidine, 0.63 g (5 mmoL) ethyl chloroacetate 0.735 g (6 mmol), 95% ethanol 10 mL, 0.492 g (5 mmol) sodium acetate.Reflux 6 h, add 20 mL water after reaction finishes, then with 20 mL benzene extraction 3 times, and combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with dehydrated alcohol recrystallization, obtains white solid n-(3,4-3,5-dimethylphenyl) glycine ethyl ester.
Second step: nthe preparation of-(3,4-dimethyl) phenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
Get n-(3,4-3,5-dimethylphenyl) glycine ethyl ester 1 g (1.2mmol), methyl aceto acetate 0.28 g (1.9mmol), 5 mL are dry, and dimethylbenzene joins in there-necked flask, after 125-130 ℃ of backflow 24 h, be cooled to normal temperature, add 15 mL sodium methylates (1 mol/L), under normal temperature, stir 48 h.After reaction finishes, in system, add 20 mL water, the dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction 3 times, combining extraction liquid, uses saturated common salt water washing, collect organic phase and with anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product.Thick product CH 3oH:CHCl 3=3:1 (volume ratio) recrystallization obtains compound n-(3,4-dimethyl) phenyl-3-ethanoyl-4-hydroxyl pyrroline-2-one.
The 3rd step: n-(3,4-3,5-dimethylphenyl)-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one.
Take n-(3, 4-3,5-dimethylphenyl)-3-ethanoyl-4-hydroxyl pyrroline-2-one 500 mg (1.9 mmol), measure 20 mL anhydrous methanols, 2 mL 50% KOH join in there-necked flask, stirring at normal temperature 20 mIn, produce a large amount of white flosss, add 10 mmol Benzaldehyde,2-methoxies, connect prolong backflow 6-8 h, TLC follows the tracks of reaction process, after reaction finishes, to system, add 10 mL water, dilute hydrochloric acid with 20% regulates pH=2-3, separate out a large amount of yellow solids, normal pressure solid collected by filtration, dry for standby, adopt column chromatography for separation (methylene dichloride: triethylamine=250:1), precipitation, add water, dilute hydrochloric acid with 20% regulates pH=2-3, with 20 mL dichloromethane extraction three times, combining extraction liquid, the target compound of removal of solvent under reduced pressure n-(3,4-3,5-dimethylphenyl)-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
All the other compounds synthetic similar to the above embodiments, does not enumerate at this.
Table 1 synthesizes n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] structure of-4-hydroxyl pyrroline-2-one compounds
Numbering Product structure
I1
I2
I3
I4
I5
I6
I7
I8
I9
I10
I11
I12
I13
I14
I15
I16
I17
I18
I19
I20
I21
I22
I23
I24
I25
I26
I27
I28
I29
I30
Synthesize n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] spectral data of-4-hydroxyl pyrroline-2-one compound.
n-p-methylphenyl-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i1)
Yellow solid, fusing point is higher than 250 ℃, yield: 52.5%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.34 (s, 3H, Ar-CH 3), 4.19 (s. 2H, N-CH 2), 7.2 (d, j=8.0 Hz, 2H, Ar-H), 7.29 (d, j=8.0 Hz, 1H, Ar-H), 7.53 (d, j=16.0 Hz, 1H, Ar-CH=), 7.54 (t, j=8.0 Hz, 2H, Ar-H), 7.7 (d, j=7.45 Hz, 1H, Ar-H), 7.8 (d, j=16 Hz, 1H, Rr-CH=), 8.28 (d, j=16.0 Hz, 1H, CO-CH=). 13cNMR (500 MHz, CDCl 3, ppm), δ: 21.0,56.3,100.0,119.7,119.9,121.5,126.4,127.6,129.7,129.9,132.2,133.8,134.2,135.0,135.1,135.1,139.9,172.5,173.3,190.4. MS (ESI-MS): m/z=388.1 [M+H +]. Anal.Calcd. For C 20h 15cl 2nO 3: C, 61.84; H, 3.99; N, 3.66. Found:C, 61.87; H, 3.89; N, 3.61.
n-p-methylphenyl-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i2)
Yellow solid, fusing point is higher than 250 ℃, yield: 52.5%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.34 (s, 3H, Ar-CH 3), 3.93 (s, 3H ,-OCH 3), 4.16 (s. 2H, N-CH 2), 6.93 (d, j=8.05 Hz, 1H, Ar-H), 7.0 (d, j=8.05 Hz, 1H, Ar-H) 7.2 (d, j=8.0 Hz, 2H, Ar-H), 7.41 (t, j=15.45 Hz, 1H, Ar-H), 7.54 (t, j=8.0 Hz, 2H, Ar-H), 7.73 (d, j=8.0 Hz, 1H, Ar-H), 7.92 (d, j=16.05 Hz, 1H, Ar-CH=), 8.28 (d, j=16.05 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 20.9,55.7,56.3,101.0,119.7,119.9,121.5,126.4,127.6,129.7,129.9,132.2,133.8,134.2,135.0,135.1,135.1,139.9,172.5,173.3,190.3. MS (ESI-MS): m/z=350.13 [M+H +]. Anal.Calcd. For C 21h 19nO 4: C, 72.00; H, 5.28; N, 3.98; Found:C, 72.19; H, 5.48, N, 4.01.
n-p-methylphenyl-3-[3-(2,3-Dimethoxyphenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i3)
Yellow solid, fusing point is higher than 250 ℃, yield: 56.5%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.34 (s, 3H, Ar-CH 3), 3.88 (s, 3H ,-OCH 3), 3.93 (s, 3H ,-OCH 3), 4.18 (s. 2H, N-CH 2), 6.99 (d, j=8.0 Hz, 1H, Ar-H), 7.12 (t, 1H, Ar-H), 7.21 (d, j=8.0 Hz, 2H, Ar-H), 7.39 (d, j=8.0 Hz, 1H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 7.90 (d, j=16.2 Hz, 1H, Rr-CH=), 8.26 (d, j=16.2 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 21.0,56.0,56.2,61.6,102.1,111.3,114.8. 114.9,119.1,119.6,119.7,119.8,124.3,129.8,134.8,139.5,147.4,149.2,153.1,173.0,174.7,190.2. MS (ESI-MS): m/z=380.15 [M+H +]. Anal.Calcd. For C 22h 21nO 5: C, 69.58; H, 5.55; N, 3.84; Found:C, 69.64; H, 5.58, N, 3.69.
n-p-methylphenyl-3-[3-(the fluoro-4-bromophenyl of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i4)
Yellow solid, fusing point is higher than 250 ℃, yield: 46.3%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.39 (s, 3H, Ar-CH 3), 4.18 (s. 2H, N-CH 2), 6.99 (d, j=8.0 Hz, 1H, Ar-H), 7.21 (t, 2H, Ar-H) 7.24 (d, j=8.0 Hz, 2H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 7.58 (s, 1H, Ar-H), 7.82 (d, j=16.0 Hz, 1H, Rr-CH=), 7.90 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 21.7,56.2,101.9,117.3,119.6,120.1,120.3,129.2,129.3,129.7,129.9,131.5,131.9,134.8,135.3,142.1,145.1,173.1,174.7,190.3. MS (ESI-MS): m/z=453.6 [M+K +]. Anal.Calcd. For C 20h 15brFNO 3: C, 57.57; H, 3.65; N, 3.64; Found:C, 57.71; H, 3.63; N, 3.37.
n-p-methylphenyl-3-[3-(3-nitrophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i5)
Yellow solid, fusing point is higher than 250 ℃, yield: 34.3%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.39 (s, 3H, Ar-CH 3), 4.22 (s. 2H, N-CH 2), 7.22 (d, j=8.0 Hz, 2H, Ar-H), 7.54 (d, j=8.0 Hz, 2H, Ar-H), 7.92 (t, 2H, Ar-H), 8.01 (d, j=16.3 Hz, 1H, Rr-CH=), 8.27 (d, j=16.3 Hz, 1H, CO-CH=). 8.46 (s, 1H, Ar-H). 13c NMR (500 MHz, CDCl 3, ppm), δ: 21.0,56.3,103.1,119.7,120.0,123.7,125.1,129.8,129.9,130.1,133.9,135.0,135.3,136.3,141.3,142.1,148.8,172.5,172.9,190.3. MS (ESI-MS): m/z=365.11 [M+H +]. Anal.Calcd. For C 20h 16n 2o 5: C, 65.86; H, 4.26; N, 7.83; Found:C, 65.93; H, 4.43; N, 7.69.
n-p-methylphenyl-3-[3-(4-aminomethyl phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i6)
Yellow solid, fusing point is higher than 250 ℃, yield: 33.6%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.34 (s, 3H, Ar-CH 3), 3.93 (s, 3H, Ar-CH 3), 4.27 (s. 2H, N-CH 2), 7.13 (d, j=8.0 Hz, 2H, Ar-H), 7.21 (d, j=8.0 Hz, 2H, Ar-H), 7.54 (d, j=8.0 Hz, 2H, Ar-H), 7.57 (d, j=7.8 Hz, 2H, Ar-H), 7.91 (d, j=16.0 Hz, 1H, Rr-CH=), 8.18 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 21.1,46.9,56.3,103.1,119.7,120.0,123.7,125.2,129.8,129.9,130.1,133.9,135.0,135.3,136.7,141.1,142.1,148.8,172.4,172.7,190.4. MS (ESI-MS): m/z=334.15 [M+H +]. Anal.Calcd. For C 21h 19nO 3: C, 65.86; H, 4.26; N, 7.83; Found:C, 65.93; H, 4.43; N, 7.69.
n-p-methylphenyl-3-[3-(4-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i7)
Yellow solid, fusing point is higher than 250 ℃, yield: 45.2%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.34 (s, 3H, Ar-CH 3), 4.18 (s. 2H, N-CH 2), 7.13 (d, j=8.0 Hz, 2H, Ar-H), 7.21 (d, j=8.0 Hz, 2H, Ar-H), 7.51 (d, j=8.0 Hz, 2H, Ar-H), 7.53 (d, j=8.0 Hz, 2H, Ar-H), 7.54 (d, j=8.0 Hz, 2H, Ar-H), 7.56 (d, j=7.7 Hz, 2H, Ar-H), 7.81 (s, 2H, CH=CH), 13c NMR (500 MHz, CDCl 3, ppm), δ: 20.9,56.3,102.4,118.7,119.6,119.8,125.7,129.7,129.7 129.9,129.9,130.3,132.4,133.5,135.0,135.2,143.3,172.8,173.9,190.3. MS (ESI-MS): m/z=398.1 [M+H +]. Anal.Calcd. For C 20h 16brNO 3: C, 60.42; H, 4.34; N, 3.61; Found:C, 60.32; H, 4.05, N, 3.52.
n-p-methylphenyl-3-[3-(2-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i8)
Yellow solid, fusing point is higher than 250 ℃, yield: 53.2%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.35 (s, 3H, Ar-CH 3), 4.19 (s. 2H, N-CH 2), 6.95 (t, 2H, Ar-H), 7.22 (d, j=8.0 Hz, 2H, Ar-H), 7.39 (t, 3H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 8.02 (d, j=16.1 Hz, 1H, Rr-CH=), 8.09 (d, j=16.1 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 20.9,56.3,102.6,119.6,119.7,119.8,125.7,128.7,129.7,129.8,129.9,130.3,132.7,133.5,135.0,135.9,140.3,172.7,173.8,190.3. MS (ESI-MS): m/z=338.5 [M+H +], 360.5 [M+Na +]. Anal.Calcd. For C 20h 16fNO 3: C, 71.75; H, 4.34; N, 4.25; Found:C, 71.21; H, 4.78; N, 4.15.
n-p-methylphenyl-3-[3-(3-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i9)
Yellow solid, fusing point is higher than 250 ℃, yield: 65.2 %, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.35 (s, 3H, Ar-CH 3), 4.20 (s. 2H, N-CH 2), 6.95 (t, 2H, Ar-H), 7.22 (d, j=8.0 Hz, 2H, Ar-H), 7.31 (t, 3H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 7.60 (s, 1H, Ar-H), 7.8 (d, j=15.8 Hz, 2H, CH=CH). 13c NMR (500 MHz, CDCl 3, ppm), δ: 21.1,56.3,102.1,119.7,120.2,123.7,125.1,129.8,129.9,130.3,133.9,135.0,135.3,136.3,141.3,142.1,148.8,172.4,172.9,190.7. MS (EMS): m/z=398.1 [M+H +]. Anal.Calcd. For C 20h 16brNO 3: C, 60.42; H, 4.34; N, 3.61; Found:C, 60.32; H, 4.05; N, 3.52.
n-p-methylphenyl-3-[3-(the fluoro-6-chloro-phenyl-of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i10)
Yellow solid, fusing point is higher than 250 ℃, yield: 38.4%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.40 (s, 3H, Ar-CH 3), 4.20 (s. 2H, N-CH 2), 7.19 (t, 1H, Ar-H), 7.23 (d, j=8.0 Hz, 2H, Ar-H), 7.40 (d, j=7.6 Hz, 2H, Ar-H), 7.54 (d. j=8.0 Hz, 2H, Ar-H), 8.04 (d, j=15.6 Hz, 1H, Rr-CH=), 8.07 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 21.1,56.2,103.2,119.6,126.3,126.6,129.2,129.5,129.9,131.4,131.8,130.3,132.1,132.3,135.4,135.6,137.7,172.6,173.2,190.3. MS (ESI-MS): m/z=416.1 [M+H +]. Anal.Calcd. For C 20h 15clFNO 3: C, 64.45; H, 3.98; N, 3.89; Found:C, 64.61; H, 4.07; N, 3.77.
n-p-methylphenyl-3-[3-(4-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl-pyrroline-2-one (compound i11)
Yellow solid, fusing point is higher than 250 ℃, yield: 34.3%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.34 (s, 3H, Ar-CH 3), 4.16 (s. 2H, N-CH 2), 6.94 (d, j=7.6 Hz, 2H, Ar-H), 7.20 (d, j=8.0 Hz, 2H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 7.64 (d, j=8.0 Hz, 2H, Ar-H), 7.73 (d, j=16.0 Hz, 1H, Rr-CH=), 7.91 (d, j=16.0Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 20.9,56.2,101.3,114.7,115.6,119.5,119.7,127.4,128.8,129.7,129.8,131.1,131.3,134.7,135.4,144.9,162.4,173.2,174.8,190.3. MS (ESI-MS): m/z=338.3 [M+H +]. Anal.Calcd. For C 20h 16fNO 3: C, 72.22; H, 5.55; N, 4.15; Found:C, 71.21; H, 4.78; N, 4.15.
n-p-methylphenyl-3-[3-(3,4-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i12)
Yellow solid, fusing point is higher than 250 ℃, yield: 45.2%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.35 (s, 3H, Ar-CH 3), 4.20 (s. 2H, N-CH 2), 7.22 (d, j=8.0 Hz, 2H, Ar-H), 7.50 (s, 1H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 7.73 (s, 2H, Ar-H), 7.77 (d, j=15.6 Hz, 1H, Rr-CH=), 7.79 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 21.0,56.3,101.9,117.1,119.6,123.5,129.2,129.3,129.6,129.9,131.7,132.4,134.6,134.8,135.2,142.1,145.1,173.2,174.7,190.1. MS (ESI-MS): m/z=388.6 [M+H +]. Anal. Calcd. For C 20h 15cl 2nO 3: C, 61.77; H, 4.10; N, 3.72; Found:C, 61.87; H, 3.89; N, 3.61.
n-p-methylphenyl-3-[3-(2,6-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i13)
Yellow solid, fusing point is higher than 250 ℃, yield: 38.4%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.35 (s, 3H, Ar-CH 3), 4.14 (s. 2H, N-CH 2), 7.20 (t, 1H, Ar-H), 7.22 (d, j=8.0 Hz, 1H, Ar-H), 7.39 (d, j=8.1 Hz, 2H, Ar-H), 7.55 (d. j=8.0 Hz, 2H, Ar-H), 8.02 (d, j=15.6 Hz, 1H, Rr-CH=), 8.05 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm) δ: 21.0,56.3,103.1,119.7,126.4,126.6,129.1,129.1,129.9,131.5,131.8,130.3,132.0,132.3,135.1,135.6,137.8,172.6,173.2,190.1. MS (ESI-MS): m/z=388.6 [M+H +]. Anal.Calcd. For C 20h 15cl 2nO 3: C, 61.89; H, 4.05; N, 3.71; Found:C, 61.87; H, 3.89; N, 3.61.
n-p-methylphenyl-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i14)
Yellow solid, fusing point is higher than 250 ℃, yield: 65.2%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.34 (s, 3H, Ar-CH 3), 4.20 (s. 2H, N-CH 2), 6.95 (t, 2H, Ar-H), 7.22 (d, j=8.0 Hz, 2H, Ar-H), 7.45 (t, 2H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 7.85 (d, j=15.5 Hz, 1H, Rr-CH=), 8.32 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 21.0,56.4,101.6,119.6,119.7,119.8,125.7,127.7,129.7 129.8,129.9,131.3,132.7,133.5,135.0,135.9,140.3,172.6,173.8,191.1. MS (ESI-MS): m/z=354.08 [M+H +]. Anal.Calcd. For C 20h 16clNO 3: C, 67.78; H, 4.66; N, 3.60; Found:C, 67.90; H, 4.56; N, 3.96.
n-p-methylphenyl-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i15)
Yellow solid, fusing point is higher than 250 ℃, yield: 55.3%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.35 (s, 3H, Ar-CH 3), 4.19 (s. 2H, N-CH 2), 7.20 (d, j=8.0 Hz, 2H, Ar-H), 7.32 (d, j=8.0 Hz, 1H, Ar-H), 7.46 (s. 1H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 7.79 (d, j=8.0 Hz, 1H, Ar-H), 7.83 (d, j=16.0 Hz, 1H, Rr-CH=), 8.21 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 20.9,56.4,101.8,117.2,119.5,123.4,129.1,129.4,129.5,129.8,131.6,132.3,134.5,134.5,135.5,142.1,145.3,173.2,174.5,190.2. MS (ESI-MS): m/z=388.6 [M+H +]. Anal.Calcd. For C 20h 15cl 2nO 3: C, 61.89; H, 4.05; N, 3.71; Found:C, 61.87; H, 3.89; N, 3.61.
n-(3,4-3,5-dimethylphenyl)-3-[3-(4-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i16)
Yellow solid, fusing point is higher than 250 ℃, yield: 63.2%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.18 (s. 2H, N-CH 2), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.34 (d, j=7.45 Hz, 1H, Ar-H), 7.40 (d. j=8.0 Hz, 2H, Ar-H), 7.45 (s, 1H, Ar-H), 7.61 (d, j=8.75 Hz, 2H, Ar-H), 7.82 (s, 2H, CH=CH). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.3,20.2,56.4,102.4,117.2,118.7,121.1,129.4,129.4,130.2,130.4,130.3,133.1,133.8,135.4,137.2,137.7,143.1,172.8,173.9,190.4. MS (ESI-MS): m/z=368.3 [M+H +]. Anal.Calcd. For C 21h 18clNO 3: C, 68.56; H, 4.99; N, 3.82; Found:C, 68.57; H, 4.93; N, 3.81.
n-(3,4-3,5-dimethylphenyl)-3-[3-(4-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i17)
Yellow solid, fusing point is higher than 250 ℃, yield: 48.8%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.18 (s. 2H, N-CH 2), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.34 (d, j=8.0 Hz, 1H, Ar-H), 7.45 (s, 1H, Ar-H), 7.56 (t, 4H, Ar-H), 7.82 (s, 2H, CH=CH 2). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.2,20.2,56.6,102.4,117.2,118.7,121.1,129.4,129.4,130.2,130.4,130.3,133.1,133.8,135.4,137.2,137.7,143.1,172.8,173.8,190.1. MS (ESI-MS): m/z=412.1 [M+H +]. Anal.Calcd. For C 21h 18brNO 3: C, 61.22; H, 4.53; N, 3.61; Found:C, 61.18; H, 4.40; N, 3.40.
n-(3,4-3,5-dimethylphenyl)-3-[3-(2-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i18)
Yellow solid, fusing point is higher than 250 ℃, yield: 56.2%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.18 (s. 2H, N-CH 2), 6.95 (t, 2H, Ar-H), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.34 (d, j=8.0 Hz, 1H, Ar-H), 7.45 (s, 1H, Ar-H), 7.85 (d, j=16.0 Hz, 1H, Rr-CH=), 8.32 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.2,20.2,56.4,101.6,119.6,119.7,119.8,125.7,127.7,129.7 129.8,129.9,131.3,132.7,133.5,135.0,135.9,140.3,172.6,173.8,191.1. MS (ESI-MS): m/z=352.1 [M+H +]. Anal.Calcd. For C 21h 18fNO 3: C, 71.12; H, 5.52; N, 4.22; Found:C, 71.78; H, 5.16; N, 3.99.
n-(3,4-3,5-dimethylphenyl)-3-[3-(3,4-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i19)
Yellow solid, fusing point is higher than 250 ℃, yield: 48.3%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.18 (s. 2H, N-CH 2), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.34 (d, j=7.5 Hz, 1H, Ar-H), 7.45 (t, 1H, Ar-H), 7.50 (s, 1H, Ar-H), 7.73 (s, 2H, Ar-H), 7.77 (d, j=16.0 Hz, 1H, Rr-CH=), 7.79 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.3,21.0,56.3,101.9,117.1,119.6,123.5,129.2,129.3,129.6,129.9,131.7,132.4,134.6,134.8,135.2,142.1,145.1,173.2,174.7,190. MS (ESI-MS): m/z=401.5 [M+H +]. Anal.Calcd. For C 21h 17cl 2nO 3: C, 62.58; H, 4.35; N, 3.64; Found:C, 62.70; H, 4.26; N, 3.48.
n-(3,4-3,5-dimethylphenyl)-3-[3-(3-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i20)
Yellow solid, fusing point is higher than 250 ℃, yield: 37.5%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.19 (s. 2H, N-CH 2), 7.14 (d, j=8.0 Hz, 1H, Ar-H), 7.31 (t, 3H, Ar-H), 7.33 (d, j=8.0 Hz, 1H, Ar-H), 7.45 (t, 1H, Ar-H), 7.60 (s, 1H, Ar-H), 7.8 (d, j=15.7 Hz, 2H, CH=CH). 13c NMR (500 MHz, CDCl 3, ppm) δ: 19.3,20.1,56.6,102.6,119.3,119.7,119.9,125.7,126.3,128.7 129.8,129.9,131.3,132.5,133.5,135.0,165.9,140.3,172.5,173.5,190.3. MS (ESI-MS): m/z=412.1 [M+H +]. Anal.Calcd. For C 21h 18brNO 3: C, 60.90; H, 4.52; N, 3.46; Found:C, 61.18; H, 4.40; N, 3.40.
n-(3,4-3,5-dimethylphenyl)-3-[3-(the fluoro-4-bromophenyl of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i21)
Yellow solid, fusing point is higher than 250 ℃, yield: 46.3%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.19 (s. 2H, N-CH 2), 6.99 (d, j=8.0 Hz, 1H, Ar-H), 7.21 (t, 2H, Ar-H) 7.24 (d, j=8.0 Hz, 2H, Ar-H), 7.55 (d, j=8.0 Hz, 2H, Ar-H), 7.58 (s, 1H, Ar-H), 7.82 (d, j=16.0 Hz, 1H, Rr-CH=), 7.90 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.1,21.0,56.7,101.9,117.3,119.6,120.1,120.3,129.2,129.3,129.7,129.9,131.5,131.9,134.8,135.3,142.1,145.1,173.1,174.7,190.3. MS (ESI-MS): m/z=432.1 [M+H +]. Anal.Calcd. For C 21h 17brFNO 3: C, 58.94; H, 3.69; N, 3.35; Found:C, 58.62; H, 3.98; N, 3.26.
n-(3,4-3,5-dimethylphenyl)-3-(3-phenyl-2-alkene-1-ketone)-4-hydroxyl pyrroline-2-one (compound i22)
Yellow solid, fusing point is higher than 250 ℃, yield: 45.3%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.19 (s. 2H, N-CH 2), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.34 (d, j=7.6 Hz, 2H, Ar-H), 7.43 (s, 2H, Ar-H), 7.46 (s, 1H, Ar-H), 7.68 (s. 2H, Ar-H), 7.87 (d, j=15.8 Hz, 1H, Rr-CH=), 7.92 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.1,21.0,56.7,101.9,117.4,119.6,123.5,129.2,129.4,129.5,129.8,131.7,132.3,134.2,134.5,135.8,142.1,145.3,173.4,174.5,191.2. MS (ESI-MS): m/z=334.14 [M+H +]. Anal.Calcd. For C 21h 19nO 3: C, 75.58; H, 5.92; N, 4.15; Found:C, 75.66; H, 5.74; N, 4.20.
n-(3,4-3,5-dimethylphenyl)-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i23)
Yellow solid, fusing point is higher than 250 ℃, yield: 62.1%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.26 (s, 3H, Ar-CH 3), 2.30 (s, 3H, Ar-CH 3), 4.20 (s. 2H, N-CH 2), 7.15 (d, j=8.0 Hz, 1H, Ar-H), 7.28 (t, j=7.8 Hz, 2H, Ar-H), 7.35 (d, j=7.6 Hz, 1H, Ar-H), 7.46 (s, 1H, Ar-H), 7.52 (d. j=7.8 Hz, 1H, Ar-H), 7.75 (d, j=7.7 Hz, 1H, Ar-H), 7.84 (d, j=16.0 Hz, 1H, Rr-CH=), 8.29 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.1,21.2,56.6,101.7,117.4,119.5,123.6,129.3,129.4,129.7,129.8,131.6,132.3,134.4,134.5,135.6,142.1,145.3,173.2,173.5,191.2. MS (ESI-MS): m/z=401.5 [M+H +]. Anal.Calcd. For C 21h 17cl 2nO 3: C, 62.83; H, 4.15; N, 3.31; Found:C, 62.70; H, 4.26; N, 3.48.
n-(3,4-3,5-dimethylphenyl)-3-[3-(3-nitrophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i24)
Yellow solid, fusing point is higher than 250 ℃, yield: 30.1%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.26 (s, 3H, Ar-CH 3), 2.30 (s, 3H, Ar-CH 3), 4.20 (s. 2H, N-CH 2), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.34 (d, j=8.0 Hz, 1H, Ar-H), 7.46 (d, j=7.5 Hz, 1H, Ar-H), 7.61 (d, 1H, Ar-H), 7.92 (t, 2H, Ar-H), 7.99 (d, 1H, Ar-H), 8.15 (d, j=16.0 Hz, 1H, Rr-CH=), 8.46 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.2,21.1,56.7,102.6,119.3,119.7,119.8,125.7,126.3,128.4 129.8,129.9,131.3,132.4,133.5,135.0,165.7,140.3,172.3,173.5,191.1. MS (ESI-MS): m/z=368.1 [M+H +]. Anal.Calcd. For C 21h 18nO 3: C, 66.30; H, 5.05, N, 8.05; Found:C, 66.66; H, 4.79; N, 7.40.
n-(3,4-3,5-dimethylphenyl)-3-[3-(the fluoro-6-chloro-phenyl-of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i25)
Yellow solid, fusing point is higher than 250 ℃, yield: 58.5%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.01 (s. 2H, N-CH 2), 6.87 (d, j=8.1 Hz, 1H, Ar-H), 7.06 (d, j=8.0 Hz, 1H, Ar-H), 7.14 (d, j=8.0 Hz, 1H, Ar-H), 7.28 (d, j=8.0 Hz, 1H, Ar-H), 7.34 (d, j=7.8 Hz, 1H, Ar-H), 7.46 (s, 1H, Ar-H), 8.31 (d, j=16.0 Hz, 1H, Rr-CH=), 8.35 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.3,21.0,56.6,102.4,118.3,118.7,118.8,125.7,126.5,128.4 129.5,129.9,130.3,132.4,133.5,135.2,165.7,140.3,172.2,173.3,190.1. MS (ESI-MS): m/z=386.1 [M+H +]. Anal.Calcd. For C 21h 17clFNO 3: C, 65.25; H, 4.31; N, 3.56; Found:C, 65.37; H, 4.44; N, 3.63.
n-(3,4-3,5-dimethylphenyl)-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i26)
Yellow solid, fusing point is higher than 250 ℃, yield: 62.1%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.18 (s. 2H, N-CH 2), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.25 (t, j=8.0 Hz, 1H, Ar-H), 7.33 (s, 1H, Ar-H), 7.42 (d, j=8.0 Hz, 1H, Ar-H), 7.45 (d. 1H, Ar-H), 7.77 (s, 1H, Ar-H), 7.84 (d, j=16.0 Hz, 1H, Rr-CH=), 8.29 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.3,20.2,56.4,102.8,117.2,120.7,121.1,127.3,127.8,129.5,130.2,133.2,133.9,135.3,136.4,137.2,137.7,138.6,172.5,173.4,190.5. MS (ESI-MS): m/z=401.5 [M+H +]. Anal.Calcd. For C 21h 17cl 2nO 3: C, 62.59; H, 4.73; N, 3.41; Found:C, 62.70; H, 4.26; N, 3.48.
n-(3,4-3,5-dimethylphenyl)-3-[3-(4-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i27)
Yellow solid, fusing point is higher than 250 ℃, yield: 65.3%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.19 (s. 2H, N-CH 2), 7.15 (d, j=8.0 Hz, 1H, Ar-H), 7.28 (m, 4H, Ar-H), 7.45 (d, j=8.0 Hz, 1H, Ar-H), 7.47 (s. 1H, Ar-H), 7.96 (d, j=16.1 Hz, 1H, Rr-CH=), 8.31 (d, j=16.1 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.3,20.2,56.4,102.5,117.4,120.3,121.3,127.3,128.3,131.0,131.8,132.7,133.9,135.4,135.9,137.2,137.3,142.1,172.9,173.6,191.0. MS (ESI-MS): m/z=352.2 [M+H +]. Anal.Calcd. For C 21h 18fNO 3: C, 70.12; H, 5.56; N, 4.12; Found:C, 71.78; H, 5.16; N, 3.99.
n-(3,4-3,5-dimethylphenyl)-3-[3-(2,6-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i28)
Yellow solid, fusing point is higher than 250 ℃, yield: 73.1%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.18 (s. 2H, N-CH 2), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.19 (t, 1H, Ar-H), 7.34 (d, j=8.0 Hz, 1H, Ar-H), 7.37 (d, j=8.0 Hz, 2H, Ar-H), 7.45 (s. 1H, Ar-H), 8.02 (d, j=16.0 Hz, 1H, Rr-CH=), 8.05 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.3,20.2,56.4,103.2,117.3,120.7,121.1,126.5,127.8,129.0,130.2,133.1,133.9,135.5,136.4,137.2,137.7,138.6,172.5,173.2,190.2. MS (ESI-MS): m/z=401.1 [M+H +]. Anal.Calcd. For C 21h 17cl 2nO 3: C, 62.11; H, 5.07; N, 4.20; Found:C, 62.70; H, 4.26; N, 3.48.
n-(3,4-3,5-dimethylphenyl)-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i29)
Yellow solid, fusing point is higher than 250 ℃, yield: 55.7%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.25 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 4.19 (s. 2H, N-CH 2), 7.16 (d, j=8.0 Hz, 1H, Ar-H), 7.30 (m, 4H, Ar-H), 7.43 (d, j=8.0 Hz, 1H, Ar-H), 7.46 (s. 1H, Ar-H), 7.86 (d, j=16.0 Hz, 1H, Rr-CH=), 8.30 (d, j=16.0 Hz, 1H, CO-CH=). 13c NMR (500 MHz, CDCl 3, ppm), δ: 19.3,20.2,56.4,102.7,117.3,120.3,121.1,127.3,128.3,130.0,131.8,132.7,133.9,135.4,135.9,137.2,137.7,140.1,172.7,173.8,190.5. MS (ESI-MS): m/z=348.2 [M+H +]. Anal.Calcd. For C 21h 18clNO 3: C, 68.07; H, 5.15; N, 4.04; Found:C, 62.70; H, 4.26; N, 3.48.
n-(3,4-3,5-dimethylphenyl)-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one (compound i30)
Yellow solid, fusing point is higher than 250 ℃, yield: 55.7%, 1h NMR (500 MHz, CDCl 3, ppm), δ: 2.21 (s, 3H, Ar-CH 3), 2.29 (s, 3H, Ar-CH 3), 3.94 (s. 3H, O-CH 3), 4.17 (s. 2H, N-CH 2), 6.90 (d, j=7.5 Hz, 1H, Ar-H), 6.93 (d, j=8.0 Hz, 1H, Ar-H), 7.14 (d, j=8.0 Hz, 1H, Ar-H), 7.30 (m, 2H, Ar-H), 7.43 (d, j=8.0 Hz, 1H, Ar-H), 7.46 (s. 1H, Ar-H), 7.74 (d, j=8.0 Hz, 1H, Ar-H), 7.95 (d, j=16.0 Hz, 1H, Rr-CH=), 8.27 (d, j=16.0 Hz, 1H, CO-CH=), carbon spectrum does not go out peak. and MS (ESI-MS): m/z=386.3 [M+H +]. Anal.Calcd. For C 22h 21nO 4: C, 72.72; H, 5.93; N, 4.09; Found:C, 72.71; H, 5.82; N, 3.85.
Embodiment nine, the inhibition activity test method of part of compounds to three kind of plant pathogenic fungies
Adopt growth rate method, with fusarium graminearum ( g. zeae), capsicum wilt bacterium ( f.oxysporum), apple decay bacterium ( c. mandshurIca) be tested object, the Antifungal Activity in Vitro of target compound is carried out to preliminary screening.Main potato dextrose agar (PDA) substratum that adopts, measuring respectively 90 mL substratum, to be divided in 200 mL triangular flasks sterilizing standby.The preparation of pastille substratum is all carried out under aseptic condition, and every kind of drug concentration is made as 50 μ g/mL.Take respectively various medicaments in 10 mL volumetric flasks, add the aqua sterilisa containing 0.1% Tween 20 to be mixed with certain density medicament, add in 90 mL PDA substratum (40-50 ℃), fully shake up, be poured in the culture dish after the sterilizing of diameter 9 cm, if three times are repeated, take that to add the solvent of equivalent be blank.During primary dcreening operation, take fusarium graminearum, capsicum wilt bacterium, apple decay bacterium is screening object, with punch tool (internal diameter 4 mm), the normal bacterium colony punching of growth is made to some bacterium cakes standby, with inoculating needle, bacterium cake is moved and receives dull and stereotyped central authorities, every ware connects a bacterium cake, be placed in 27 ℃ of saturated humidity constant incubators and cultivate, when contrast is covered with, measure colony diameter.Each bacterium colony is measured 2 times by right-angled intersection method, represents the size of bacterium colony with its mean number, and the calculation formula of bacteriostasis rate is as follows:
I%＝[(C－T)/(C－0.4)]×100
I is inhibiting rate, and C is blank diameter, and T is for processing diameter
table 2 n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-the inhibition (500 of 4-hydroxyl pyrroline-2-one compounds to plant epiphyte μg/mL)
By table 2can find out, be 500 in concentration μduring g/mL, compound i2, i3, i16, ithe inhibiting rate of 18 pairs of fusarium graminearums is respectively 36.0%, 25.2%, 25.9%, 26.1%, compound i2, i3, i16, ithe inhibiting rate of 18 pairs of capsicum wilt bacterium is respectively 39.6%, 19.4%, 21.3%, 25.2%.
Embodiment ten, compound are 500 μresisting tobacco mosaic virus live body therapeutic activity test under g/mL concentration.
Select the Nicotiana glutinosa that growing way is consistent, with phosphoric acid buffer, TMV crude extract is diluted to suitable concentration, 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, with clear water, rinse.After blade is dry, at Zuo Banye, spread compound solution, the solvent that right half leaf spreads matched doses compares.In illumination box, moisturizing is cultivated subsequently, controls 23 ± 1 ℃ of temperature, 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.
On half leaf of blank, present obvious withered spot, after test 3 ~ 4 d, just can investigate, 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.
Expression mode: Y=(C-A)/C * 100%
Wherein: Y is the inhibiting rate of compound to plant virus.
C is control group (right half leaf) withered spot number, unit: individual.
A is compound treatment group (Zuo Banye) withered spot number, unit: individual.
Wherein control group (right half leaf) withered spot number and compound treatment group (Zuo Banye) withered spot number can be joined mean number or each the withered spot sum of organizing repetition repeating by each group.Each process be with oneself second half in contrast, then the processing that one group of commodity Ningnanmycin is set is as a comparison.
table 3 n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one compounds is to tobacco mosaic virus (TMV) live body treatment inhibition (500 μg/mL)
From table 3can find out, when concentration is 500 μduring g/mL, it is active that target compound has certain inhibition to TMV, compound i13, ithe inhibition activity of 15 pairs of tobacco mosaic virus (TMV) live body treatments is respectively 60.2%, 61.2%, higher than contrast medicament Ningnanmycin, i16, i22, ithe inhibition activity of 28 pairs of tobacco mosaic virus (TMV) live body treatments is respectively 55.2%, 49.9%, 47.3%, a little less than the inhibition activity 55.6% of contrast medicament Ningnanmycin.To the structure of compound and biologically active data analysis, find, when the substituting group on phenyl ring is electron-withdrawing group, compound i15 activity is the strongest.
Embodiment 11, compound are 250 μresisting tobacco mosaic virus live body therapeutic activity test under g/mL concentration.
table 4 n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one compounds is to tobacco mosaic virus (TMV) live body treatment inhibition (250 μg/mL)
From table 4can find out, when concentration is 250 μduring g/mL, it is active that part target compound has certain inhibition to TMV, compound i7, i14, i15, i16, i28 inhibition activity is respectively 32.3%, 32.1%, 35.7%, 35.9%, 32.1%, a little less than the inhibition activity 45.1% of contrast medicament Ningnanmycin.

Claims (6)

1. n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one compounds, its general structure is as follows:
( I)
R wherein 1be 2,3-dichloro, 2-methoxyl group, 2,3-dimethoxy, the fluoro-4-bromine of 2-, 3-nitro, 4-methyl, 4-bromine, 2-fluorine, 3-bromine, the fluoro-6-chlorine of 2-, 4-fluorine, 3,4-dichloro, 2,6-dichloro, 2-chlorine, 4-chlorine, hydrogen;
R 2for 4-methyl, 3,4-dimethyl.
2. compound according to claim 1, is characterized in that synthetic compound is as follows:
I1 N-p-methylphenyl-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I2 N-p-methylphenyl-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I3 N-p-methylphenyl-3-[3-(2,3-Dimethoxyphenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I4 N-p-methylphenyl-3-[3-(the fluoro-4-bromophenyl of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I5 N-p-methylphenyl-3-[3-(3-nitrophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I6 N-p-methylphenyl-3-[3-(4-aminomethyl phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I7 N-p-methylphenyl-3-[3-(4-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I8 N-p-methylphenyl-3-[3-(2-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I9 N-p-methylphenyl-3-[3-(3-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I10 N-p-methylphenyl-3-[3-(the fluoro-6-chloro-phenyl-of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I11 N-p-methylphenyl-3-[3-(4-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I12 N-p-methylphenyl-3-[3-(3,4-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I13 N-p-methylphenyl-3-[3-(2-6-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I14 N-p-methylphenyl-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I15 N-p-methylphenyl-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I16 N-(3,4-3,5-dimethylphenyl)-3-[3-(4-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I17 N-(3,4-3,5-dimethylphenyl)-3-[3-(4-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I18 N-(3,4-3,5-dimethylphenyl)-3-[3-(2-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I19 N-(3,4-3,5-dimethylphenyl)-3-[3-(3,4-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I20 N-(3,4-3,5-dimethylphenyl)-3-[3-(3-bromophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I21 N-(3,4-3,5-dimethylphenyl)-3-[3-(the fluoro-4-bromophenyl of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I22 N-(3,4-3,5-dimethylphenyl)-3-(3-phenyl-2-alkene-1-ketone)-4-hydroxyl pyrroline-2 ketone I23 N-(3,4-3,5-dimethylphenyl)-3-[3-(2,3-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I24 N-(3,4-3,5-dimethylphenyl)-3-[3-(3-nitrophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I25 N-(3,4-3,5-dimethylphenyl)-3-[3-(the fluoro-6-chloro-phenyl-of 2-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I26 N-(3,4-3,5-dimethylphenyl)-3-[3-(2,4 dichloro benzene base)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I27 N-(3,4-3,5-dimethylphenyl)-3-[3-(4-fluorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I28 N-(3,4-3,5-dimethylphenyl)-3-[3-(2,6-dichlorophenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I29 N-(3,4-3,5-dimethylphenyl)-3-[3-(2-chloro-phenyl-)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone I30 N-(3,4-3,5-dimethylphenyl)-3-[3-(2-p-methoxy-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2 ketone
Each compound structure is as follows:
I1 I2 I3 I4 I5 I6 I7 I8 I9 I10 I11 I12 I13 I14 I15 I16 I17 I18 I19 I20 I21 I22 I23 I24 I25 I26 I27 I28 I29 I30
。
3. the application of compound in preparing plant epiphyte resisting and plant virus medicine as claimed in claim 1 or 2.
4. the application of compound according to claim 3 in preparing plant epiphyte resisting and plant virus medicine, is characterized in that medicine and medicament for the preparation of resisting tobacco mosaic virus, fusarium graminearum, capsicum wilt bacterium, Valsa mali.
5. as claimed in claim 1 n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] synthetic method of-4-hydroxyl pyrroline-2-one compounds, it is characterized in that with substituted aniline, ethyl chloroacetate, methyl aceto acetate, substituted benzaldehyde is raw material, take ethanol, dimethylbenzene, methyl alcohol as solvent is substituted, closed loop, aldol reaction be synthetic, its synthetic route is:
。
6. according to claim 5 n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] synthetic method of-4-hydroxyl pyrroline-2-one compounds, it is characterized in that synthesis step and processing condition are:
The first step: nthe preparation of-phenylglycine ethyl ester;
To adding substituted aniline, ethyl chloroacetate, 95% ethanol and sodium acetate in there-necked flask, mol ratio wherein: substituted aniline: ethyl chloroacetate: sodium ethylate=1:1:1-1:1.2:1, every 5mmol substituted aniline adds 95% ethanol 10 mL, reflux, TLC follows the tracks of reaction process, after reaction finishes, adds water, then with benzene, extract, combining extraction liquid, removal of solvent under reduced pressure obtains red-purple solid, with the white solid of dehydrated alcohol recrystallization n-phenylglycine ethyl ester;
Second step: nthe preparation of-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one;
Get substituted-phenyl glycine ethyl ester, methyl aceto acetate, dry dimethylbenzene joins in there-necked flask, at 125-130 ℃ of 24 h that reflux, mol ratio wherein: substituted-phenyl glycine ethyl ester: methyl aceto acetate=1:1-1:1.5, every 1.3 mmol substituted-phenyl glycine ethyl esters add the dry dimethylbenzene of 5 ml, TLC follows the tracks of reaction process, after raw material reaction is complete, be cooled to normal temperature, by 1.3 mmol substituted-phenyl glycine ethyl esters, be that to add concentration be 1 mol/L sodium methylate 15 mL to standard, under normal temperature, stir 48 h, TLC follows the tracks of reaction process, after reaction finishes, in system, add 20 mL water, with 20% dilute hydrochloric acid, be adjusted to pH=2-3, with 20mL dichloromethane extraction 3 times, combining extraction liquid, use saturated common salt water washing, collect organic phase and use anhydrous magnesium sulfate drying, remove by filter magnesium sulfate, removal of solvent under reduced pressure obtains thick product,
Thick product obtains solid by methylene dichloride and recrystallizing methanol n-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one;
The 3rd step: n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone] preparation of-4-hydroxyl pyrroline-2-one:
Take n-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one, adds anhydrous methanol and 50% KOH to join in there-necked flask, every 2 mmol n-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one adds anhydrous methanol 20 mL, 50% KOH 2mL, and stirring at normal temperature 20 minutes, produces a large amount of white flosss, adds substituted benzaldehyde, wherein mol ratio: n-replacement-3-ethanoyl-4-hydroxyl pyrroline-2-one: substituted benzaldehyde=1:5; connect prolong backflow 6-8 h; TLC follows the tracks of reaction process; after reaction finishes, to system, add 10 mL water, with 20% dilute hydrochloric acid, be adjusted to pH=2-3; separate out a large amount of yellow solids; normal pressure solid collected by filtration, dry for standby, adopts column chromatography for separation to obtain target compound n-replacement-3-[3-(substituted-phenyl)-2-alkene-1-ketone]-4-hydroxyl pyrroline-2-one.
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