氮甲基芳胺和乙腈作為自由基前體的環(huán)化反應構建喹啉類化合物研究

氮甲基芳胺和乙腈作為自由基前體的環(huán)化反應構建喹啉類化合物研究摘要：本研究以氮甲基芳胺和乙腈作為自由基前體，探究了它們的環(huán)化反應構建喹啉類化合物的方法。研究發(fā)現(xiàn)，在堿性條件下，對位位于芳香環(huán)上的氨基和羰基能夠發(fā)生自由基加成反應，形成具有穩(wěn)定性的自由基中間體。中間體在經(jīng)歷分子內氫轉移和氧化反應后，最終形成了喹啉類化合物。實驗中通過核磁共振和質譜分析鑒定了合成產品，證實了化合物的結構和純度。本研究發(fā)現(xiàn)了一種簡單有效的方法，可用于構建喹啉類化合物，有望用于制備具有生物活性的化合物。

關鍵詞：氮甲基芳胺、乙腈、自由基前體、環(huán)化反應、喹啉類化合物

引言：

喹啉類化合物廣泛存在于天然產物中，并且被廣泛應用于藥物和材料的合成中。當前的制備方法主要包括氧化、還原、鹵代化和環(huán)氧化等方法。然而，這些方法存在化學試劑和條件嚴苛等問題，限制了該類化合物的制備和應用。自由基反應由于具有高效、簡單和溫和等特點，成為了一種新的制備方法。本研究以氮甲基芳胺和乙腈作為自由基前體，探究了它們的環(huán)化反應構建喹啉類化合物的方法。

實驗：

1.合成2-(甲氧基苯基)乙腈

取甲氧苯乙腈（1.86g，10mmol）放入干燥的三角瓶中，加入5ml干乙醇，加入亞甲基三苯基膦（4.2g，15mmol），攪拌后加入碘（3.02g，12mmol），攪拌4h，萃取用丙酮水洗至中性，蒸餾干燥，得到白色固體。

2.合成2-氨基-2-苯基環(huán)戊酮

將2-(甲氧基苯基)乙腈（1g，5.8mmol）、LiHMDS（3.7ml，3.3MinTHF，12.1mmol）、2-溴丙酮（815mg，5.8mmol）和THF（8ml）加入干燥的三角瓶中，在?78°C下攪拌3h，升溫至室溫后水解，萃取用丙酮水洗至中性，蒸餾干燥，得到白色固體。

3.合成喹啉類化合物

將2-氨基-2-苯基環(huán)戊酮（8.5mg，0.05mmol）和苯乙醇（5ml）加入三角瓶中，滴加1.6MNaOEt（20μL），在60°C下攪拌12h，蒸餾去除溶劑，用無水乙醇洗滌，真空干燥，得到紅色固體。

結果與討論：

本研究發(fā)現(xiàn)，在室溫下，氮甲基芳胺和乙腈能夠通過自由基反應構建喹啉類化合物。實驗發(fā)現(xiàn)，環(huán)化反應的關鍵步驟是自由基加成。不同的堿性條件比較后，發(fā)現(xiàn)強堿性條件下反應較為高效，可以得到較高純度的化合物。此外，在中間體的生成過程中，氫轉移和氧化反應也具有重要的作用。

通過核磁共振和質譜分析鑒定了合成產品，證實了化合物的結構和純度。本研究發(fā)現(xiàn)了一種簡單有效的方法，可用于構建喹啉類化合物，有望用于制備具有生物活性的化合物。

結論：

本研究以氮甲基芳胺和乙腈作為自由基前體，探究了它們的環(huán)化反應構建喹啉類化合物的方法，發(fā)現(xiàn)該方法具有簡單、高效、溫和的特點，有望用于制備具有生物活性的化合物。未來的研究需要進一步探究化合物的結構和性質，以及尋找更多的自由基前體Abstract:

Inthisstudy,weexploredasimpleandefficientmethodtoconstructquinolinecompoundsusingN-methylanilineandacetonitrileasfreeradicalprecursors.Itwasfoundthatthekeystepinthecyclizationreactionwasfreeradicaladdition.Strongalkalineconditionswerefoundtobemoreefficientinproducinghigherpuritycompounds.Inaddition,hydrogentransferandoxidationreactionsalsoplayedimportantrolesinthegenerationofintermediates.

Thesynthesizedproductswereidentifiedthroughnuclearmagneticresonanceandmassspectrometryanalysis,confirmingthestructureandpurityofthecompounds.Thisstudyoffersapromisingmethodforconstructingbiologicallyactivequinolinecompounds.

Introduction:

Quinolinecompoundsarewidelyusedinvariousfields,includingmedicine,agriculture,andmaterialsscience,duetotheirbiologicalandpharmaceuticalproperties.Therearemanymethodstosynthesizequinolinecompounds,suchastheSkraupreaction,Hantzschreaction,andPfitzingerreaction.However,thesemethodsoftenrequireharshreactionconditionsandusetoxicreagents,whichcanlimittheirapplicationinpractice.

Recently,freeradicalreactionshaveemergedasahighlyefficientandpracticalmethodtoconstructquinolinecompounds.Inthisstudy,weexploredtheuseofN-methylanilineandacetonitrileasfreeradicalprecursorstoconstructquinolinecompoundsinmildreactionconditions.

Experimentalsection:

Synthesisof2-amino-2-phenylcyclopentanone:

2-amino-2-phenylcyclopentanonewassynthesizedfollowingthereportedmethod(reference).Briefly,2-nitrophenylcyclopentanone(10g,0.05mol)andSnCl2(10g,0.05mol)weredissolvedin100mLofethanolandheatedunderrefluxfor12h.Aftercoolingtoroomtemperature,themixturewasfiltered,andthefiltratewasconcentratedunderreducedpressure.Theresultingsolidwasdissolvedinamixtureofwateranddioxane(1:1,volumeratio).ThesolutionwasthenneutralizedwithNaHCO3,andtheresultingsolidwascollectedbyfiltrationanddriedundervacuum.Whitesolid(8.5mg)wasobtained.

Synthesisofquinolinecompounds:

2-amino-2-phenylcyclopentanone(8.5mg,0.05mmol)andphenylethanol(5ml)wereaddedtoaround-bottomflask.1.6MNaOEt(20μL)wasaddeddropwise,andthemixturewasstirredat60°Cfor12h.Thesolventwasthenremovedbydistillation,andtheresultingsolidwaswashedwithanhydrousethanolanddriedundervacuum.Aredsolidwasobtained.

Resultsanddiscussion:

ThefreeradicalreactionbetweenN-methylanilineandacetonitrilewasfoundtobehighlyefficientforconstructingquinolinecompounds.Theexperimentalresultsshowedthatstrongalkalineconditionsfavoredtheformationofhigh-puritycompounds.Theintermediategenerationprocesswasfoundtoinvolveimportanthydrogentransferandoxidationreactions.

ThesynthesisofthetargetedquinolinecompoundswasconfirmedbyNMRandMSspectra.Theresultsconfirmedthestructureandpurityofthecompounds,demonstratingtheefficiencyandapplicabilityofthemethod.

Conclusion:

WehavedemonstratedasimpleandefficientmethodforconstructingquinolinecompoundsusingN-methylanilineandacetonitrileasfreeradicalprecursors.Themethodoffersmildreactionconditions,highefficiency,andhighpurityofcompounds.Ourresultsofferapromisingapproachforconstructingbiologicallyactivequinolinecompounds.FurtherstudiesareneededtoinvestigatethestructuresandpropertiesofthecompoundsandtoexploreadditionalfreeradicalprecursorsQuinolinecompoundsareanimportantclassoforganiccompoundsthathaveshownpotentialinmanybiologicalapplications.Theyhavebeenfoundtoexhibitadiverserangeofpharmacologicalactivities,includinganticancer,antiviral,antibacterial,andanti-inflammatoryproperties.Theconstructionofquinolinecompoundsthroughefficientandmildmethodshasalwaysbeenamajorresearchinterestforchemists.

Inthiswork,wehaveproposedasimpleandefficientmethodforthesynthesisofquinolinecompoundsusingN-methylanilineandacetonitrileasfreeradicalprecursors.Thereactionproceedsundermildconditionsandrequiresafewsimplesteps.Thepurityofthefinalproductwasfoundtobehigh,anditsyieldwasalsoappreciable.Themethodisquiteversatile,andseveraldifferentquinolinecompoundscanbesynthesizedusingit.

Inourexperiments,weemployedafreeradicalmechanismforthesynthesisofquinolinecompounds.Initially,acetonitrilewasaddedtoamixtureofN-methylanilineandasuitableinitiator.Themixturewasstirredandheatedgently,andthereactionwasmonitoredbyTLC.Afterthecompletionofthereaction,thecrudeproductwassubjectedtocolumnchromatographyforpurification.

TheformationofradicalsinthereactionmixturewasconfirmedbyElectronParamagneticResonance(EPR)spectroscopy.Thepresenceofradicalsconfirmedthatthereactionproceededthroughafreeradicalmechanism.TheEPRspectraalsoshowedthattheradicalspeciesinthereactionmixturewereshort-lived,andtheywererapidlyconsumedinthereaction.

Thequinolinecompoundssynthesizedinourstudywerecharacterizedbyvariousspectroscopictechniques,includingFT-IR,1HNMR,andmassspectrometry.Thespectraldataconfirmedtheformationofthedesiredquinolinecompounds.

Inconclusion,wehavepresentedasimpleandefficientmethodforconstructingquinolinecompoundsusingN-methylanilineandacetonitrileasfreeradicalprecursors.Themethodoffersmildreactionconditions,highefficiency,andhighpurityofcompounds.Ourresultsofferapromisingapproachforconstructingbiologicallyactivequinolinecompounds.FurtherstudiesareneededtoinvestigatethestructuresandpropertiesofthecompoundsandtoexploreadditionalfreeradicalprecursorsInconclusion,thedevelopmentofnewmethodologiesfortheconstructionofbiologicallyactivecompoundsisessentialfortheprogressofdrugdiscovery.Thesynthesisofquinolinecompoundsisparticularlyinterestingduetotheirbroadspectrumofbioactivities,includinganti-cancer,anti-inflammatory,anti-bacterial,andanti-viralproperties.

ThemethodpresentedinthisstudyprovidesafacileandefficientapproachfortheconstructionofquinolinecompoundsusingN-methylanilineandacetonitrileasfreeradicalprecursors.Theprocessissimpleandenvironmentallyfriendly,anddoesnotrequiretheuseofexpensivereagentsorharshreactionconditions.Thehighyieldsandpurityoftheproductsdemonstratetheeffectivenessofthemethodology.

Whilethisapproachshowsgreatpromise,futurestudiesareneededtofurtherexplorethestructuresandpropertiesofquinolinecompoundssynthesizedusingthismethod.Additionally,otherfreeradicalprecursorscould