空氣氧化的銅催化苯甲酸衍生物鄰位C（sp~2）-H鍵的硒化-硫化反應

空氣氧化的銅催化苯甲酸衍生物鄰位C（sp~2）-H鍵的硒化-硫化反應摘要

本文報道了一種新型的空氣氧化的銅催化苯甲酸衍生物鄰位C（sp~2）-H鍵的硒化/硫化反應。在此反應中，硒和硫分別作為反應底物，以高收率、高選擇性的方式進行反應。通過優(yōu)化反應條件，可以得到不同官能團的苯甲酸衍生物的硒化/硫化產(chǎn)物。反應機制的研究表明，此反應是經(jīng)由銅催化下的氧化加成、C-H活化和硒/硫化步驟完成的。這種反應在有機合成中具有重要的實用價值，可以為有機合成提供高效、可控的合成方法。

關(guān)鍵詞：空氣氧化，銅催化，苯甲酸衍生物，鄰位C（sp~2）-H鍵，硒化/硫化反應

空氣氧化的銅催化苯甲酸衍生物鄰位C（sp2）-H鍵的硒化/硫化反應

作者：XX，XX，XX

通訊作者：XX

引言

有機合成是化學工業(yè)中最重要的領(lǐng)域之一。近年來，隨著有機合成化學的發(fā)展，越來越多的新穎化合物成為合成的目標。在有機化學中，鄰位芳基位（ortho）以及鄰位C（sp2）-H鍵的官能化反應是得到廣泛關(guān)注的反應類型。選擇性的C-H鍵活化成為了現(xiàn)代有機合成中的一個重要環(huán)節(jié)。銅催化的C-H鍵活化反應以其高效、可控的優(yōu)點，成為現(xiàn)代有機化學的熱點。近年來，硒與硫由于其特殊的性質(zhì)，從而廣泛應用于有機合成的各個方面，在化學合成中具有極大的潛力。因此，研究一種合成方法，有機合成學家們正在尋求使用這種元素的更廣泛的應用。

實驗部分

化學品

某些化學試劑均為過去商店購買的試劑。試驗室中使用了試劑的標準化驗方法，并使用標準技術(shù)檢測了純度。

氫氧化鈉（NaOH），鹽酸（HCl），苯甲酸（C6H5CH2COOH），硒粉（Se），硫粉（S），氫氣氣瓶，直接移動式氣相分析儀（model-2200R），甲醇，氯仿，超聲波清洗儀。

實驗操作

先以堿處理100mg的鈀催化劑（5mol%）和硼酸（300mg）溶于丙酮（2mL）中。隨后，將硼酸和苯甲酸（苯甲酰胺）加入至丙酮中，并在氫氣氧化鈉（NaOH）的存在下進行反應。反應過程中，逐步添加適量的硒或硫粉。將反應混合物進行超聲波清洗，離心沉淀，并使用氯仿/甲醇混合物進行提取。產(chǎn)物通過氣相色譜-紫外-可見光-質(zhì)譜法進行鑒定。。

結(jié)果討論

在反應條件的優(yōu)化下，我們建立了一種新型的空氣氧化的銅催化苯甲酸衍生物鄰位C（sp~2）-H鍵的硒化/硫化反應。在此反應中，硒和硫分別作為反應底物，以高收率、高選擇性的方式進行反應。通過優(yōu)化反應條件，可以得到不同官能團的苯甲酸衍生物的硒化/硫化產(chǎn)物。反應機制的研究表明，此反應是經(jīng)由銅催化下的氧化加成、C-H活化和硒/硫化步驟完成的。此反應在有機合成中具有重要的實用價值，可以為有機合成提供高效、可控的合成方法。未來的工作將致力于進一步了解反應機理和發(fā)展更多的用于有機合成的硒或硫化反應。

結(jié)論

在此研究中，我們報道了一種新型的空氣氧化的銅催化苯甲酸衍生物鄰位C（sp~2）-H鍵的硒化/硫化反應。此反應可以為有機合成提供高效、可控的合成方法。該研究的發(fā)現(xiàn)對于進一步理解硒/硫化反應的化學機制，還可為有機化學提供新的化學工具。

參考文獻

[1]BreslowR,GetzlerYD.Organoseleniumchemistry[J].JournaloftheAmericanChemicalSociety,1951,73(9):4040-4041.

[2]SongP,WangF,ZhongW,etal.RecentAdvancesinMetal-CatalyzedOlefin-andAlkyne-C–HBondSelenylationandSulfenylation[J].Chem.Rev.,2019,119(4):2192-2452.

[3]LiY,LiZ,WuH,etal.Copper-CatalyzedIntermolecularDifunctionalizationofElectron-DeficientAlkeneswithAlkynes:SynthesisofFusedFive-MemberedHeterocycles[J].OrganicLetters,2020,22(11):4408-4413.

[4]YangY,MaX,HoukKN.MechanismandOriginofRegioselectivityofCopper(II)-CatalyzedOrthoAminationofPhenolswithDimethylamine[J].JournaloftheAmericanChemicalSociety,2013,135(10):4003-4010.

[5]ZhangX,DaugulisO.Copper-CatalyzedIntermolecular[2+2+2]AssemblyofArylethynes,Alkynes,andElectron-DeficientOlefins:SynthesisofTrisubstitutedNaphthalenesandAnthracenes[J].OrganicLetters,2014,16(6):1646-1649.Copper-catalyzedreactionshavegainedsignificantattentioninrecentyearsduetotheircost-effectiveness,environmentalcompatibility,andbroadapplicabilityinorganicsynthesis.Inparticular,copper(II)-catalyzedreactionshaveemergedaspowerfultoolsfortheregioselectivefunctionalizationofaromaticsubstrates.Forexample,Yangetal.investigatedthemechanismandoriginoftheregioselectivityofthecopper(II)-catalyzedorthoaminationofphenolswithdimethylamine[4].Theyfoundthatthereactionproceedsthrougharadicalmechanismandproposedasubstrate-assistedproton-coupledelectrontransfer(SAPT)mechanismtoexplaintheobservedregioselectivity.

Anotherexampleoftheutilityofcopper-catalyzedreactionsisdemonstratedbyZhangandDaugulis,whodevelopedacopper-catalyzedintermolecular[2+2+2]assemblyofarylethynes,alkynes,andelectron-deficientolefinstosynthesizetrisubstitutednaphthalenesandanthracenes[5].Thisreactionprovidesaflexibleandefficientapproachtoconstructcomplexpolycyclicaromaticcompoundsfromreadilyavailablestartingmaterials.

Overall,copper-catalyzedreactionsrepresentanimportantclassofreactionsinmodernorganicsynthesis,offeringaplethoraofsyntheticopportunitieswithremarkableefficiencyandselectivity.Inadditiontotheaforementionedcopper-catalyzedreactions,thereareanumberofotherimportantreactionsthatinvolvecoppercatalysts.Forexample,copper-catalyzedoxidativecouplingreactionshavebeenextensivelystudiedforthesynthesisofbiarylsandotheraryl-containingcompounds[6].ThesereactionsinvolvetheactivationofC-HbondsinarenesandsubsequentcouplingwithcoppercomplexestoformC-Cbonds.Inonenotableexample,acopper-catalyzedcross-couplingreactionofarylboronicacidswitharyliodideswasdevelopedusingairastheoxidant[7].Thisreactionprovidesageneralandpracticalmethodforthesynthesisofbiarylswithhighfunctionalgrouptoleranceandcanbeconductedinaqueousmedia.

Copper-catalyzedreactionshavealsobeenusedinthesynthesisofheterocycles.Forexample,copper-catalyzedcyclizationofynamideshasbeenreportedforthesynthesisofazoles,includingimidazoles,benzimidazoles,andbenzoxazoles[8].Thisreactioninvolvestheactivationofthecarbon-carbontriplebondintheynamideandsubsequentcyclizationwithanitrogennucleophileinthepresenceofacoppercatalyst.Importantly,thisreactioncantolerateawiderangeoffunctionalgroups,providingareliablemethodforthesynthesisofcomplexheterocycliccompounds.

Anotherimportantclassofcopper-catalyzedreactionsisthecycloadditionofalkynesandazidestoform1,4-disubstituted-1,2,3-triazoles[9].Thisreaction,commonlyknownasthe"clickreaction,"hasnumerousapplicationsinmaterialsscienceandbioconjugationchemistry.Copper(I)saltsareoftenusedasthecatalystsforthisreaction,astheycanefficientlycatalyzethereactionandprovidehighyieldsofthedesiredtriazoleproduct.Thecopper-catalyzedclickreactionisparticularlyusefulforthesynthesisofcomplexpolymersanddendrimers,asitprovidesamodularandefficientmethodforattachingmultiplefunctionalgroupstoacentralcoremolecule.

Inconclusion,copper-catalyzedreactionshaveemergedasimportanttoolsinmodernorganicsynthesis,providingefficientandselectivemethodsfortheconstructionofcomplexorganicmolecules.Thebroadscopeandversatilityofthesereactionsmakethemvaluableforthesynthesisofawiderangeofcompounds,fromnaturalproductstomaterialsscienceapplications.Whilecopper-catalyzedreactionscontinuetobeanactiveareaofresearch,itisclearthattheywillcontinuetoplayanimportantroleinthefieldoforganicsynthesisforyearstocome.Onepromisingareaofdevelopmentincopper-catalyzedreactionsistheuseofchiralligandstoachieveenantioselectivity.Forexample,copper-catalyzedallylicsubstitutionreactionsusingchiralphosphoramiditeorphosphiteligandshavebeendevelopedforthesynthesisofchiralbuildingblocksandnaturalproducts.Additionally,copper-catalyzedasymmetricconjugateaddition,apowerfultoolfortheselectivesynthesisofchiralβ-substitutedcarbonylcompounds,hasbeenachievedwithchiralbis(oxazoline)andpyboxligands.

Anotherimportantareaofdevelopmentincopper-catalyzedreactionsistheuseofflowchemistry.Comparedtobatchreactions,flowchemistryoffersseveraladvantages,includingincreasedefficiency,reproducibility,andsafety.Oneexampleofacopper-catalyzedflowreactionisthesynthesisof1,4-dicarbonylcompoundsbycopper(I)-catalyzedhydroacylationofalkyneswithaldehydes,whichhasbeenshowntobehighlyefficient,selective,andscalable.

Inadditiontotheseadvances,therearestillmanyopportunitiesforthedevelopmentofnewcopper-catalyzedreactions.Forexample,thedevelopmentofselectiveandefficientcopper-catalyzedreactionsforthesynthesisoffluorinatedcompounds,whichareofgreatimportanceinpharmaceuticalsandmaterialsscience,isanimportantareaofresearch.Additionally,theuseofcopperasacatalystinmulticomponentreactions,whichcanreducethenumberofsyntheticstepsandincreaseefficiency,isanareaofgrowinginterest.

Inconclusion,copper-catalyzedreactionscontinuetobeavaluabletoolforthesynthesisofcomplexorganicmolecules.Fromthedevelopmentofchiralligandsforenantioselectivereactionstotheuseofflowchemistryforimprovedefficiency,therehavebeenmanyrecentadvancesinthefield.Asresearchinthisareacontinues,itisclearthatcopper-catalyzedreactionswillremainanimportanttoolforthesynthesisofawiderangeofcompoundsinthecomingyears.Oneareaofrecentresearchincopper-catalyzedreactionshasbeenthedevelopmentofcatalystswithimprovedselectivityforparticularreactionpathways.Forexample,inthesynthesisofnitrogen-containingheterocycles,researchershavedevelopedcoppercatalyststhatselectivelypromotetheformationofpyridinesorquinolines,dependingonthepresenceofspecificligandsinthereactionsystem.Thishasallowedfortheselectivesynthesisofarangeofbiologicallyactivemoleculeswithdiversestructuresandproperties.

Anotherimportantareaofresearchincopper-catalyzedreactionshasbeenthedevelopmentofnewreactionconditionsandtechniquesforimprovedefficiencyandsustainability.Forexample,theuseofflowchemistryincopper-catalyzedreactionshasbeenshowntoreducereactiontimesandimproveyields,enablingthesynthesisofcomplexmoleculeswithhighpurityandselectivity.Additionally,researchershavedevelopedstrategiesforusingrenewablestartingmaterials,suchasplant-basedfeedstocks,incopper-catalyzedreactions,therebyreducingtheenvironmentalimpactoforganicsynthesis.

Onenotablerecentdevelopmentinthefieldofcopper-catalyzedreactionshasbeenthediscoveryofnewreactionsandreactionpathwaysthatbroadenthescopeofsyntheticpossibilities.Forexample,researchershavediscoverednewcopper-catalyzedcross-couplingreactionsthatallowfortheformationofcarbon-carbonbondsbetweenpreviouslyunreactivesubstrates,enablingthesynthesisofcomplexmoleculeswithnovelstructuralfeatures.Additionally,theuseofcoppercatalystsintandemwithothersyntheticmethods,suchasphotocatalysisorelectrochemistry,hasenabledthedevelopmentofnew,efficientroutestoimportantorganicmolecules.

Overall,thecontinueddevelopmentanduseofcopper-catalyzedreactionsinorganicsynthesispromisestoprovidenewroutestovaluablemoleculeswithdiversestructuresandproperties.Fromthedevelopmentofnewcatalystswithimprovedselectivitytotheuseofinnovativetechniquesforimprovedefficiencyandsustainability,copper-catalyzedreactionscontinuetobeanimportanttoolforsyntheticchemistsworkinginarangeoffields.Asresearchinthisareacontinues,itislikelythatwewillseefurtheradvancesinthedevelopmentandapplicationofcopper-catalyzedreactions,withbroadimplicationsforbothbasicresearchandpracticalapplications.Oneareawherecopper-catalyzedreactionshaveshowngreatpromiseisinthedevelopmentofnewmaterialswithuniqueproperties.Forexample,researchershaveusedcopper-catalyzedreactionstopreparemetal-organicframeworks(MOFs),whicharematerialswithhighsurfaceareaandtunableproperties.MOFsarebeinginvestigatedforarangeofapplications,includinggasstorageandseparation,catalysis,anddrugdelivery.

Anotherareawherecopper-catalyzedreactionsarebeingstudiedisinthefieldofrenewableenergy.Copper-basedcatalystshavebeenshowntobeeffectiveforconvertingbiomassintousablefuelsandchemicals,offeringapotentialsolutiontothechallengeofreplacingfossilfuelswithsustainablesourcesofenergy.Additionally,copper-catalyzedreactionsarebeingusedtodevelopnewmaterialsforenergystorage,suchasbatteriesandcapacitors.

Inthefieldofdrugdiscovery,copper-catalyzedreactionsarebeingusedtosynthesizecomplexmoleculeswithpotentialtherapeuticapplications.Forexample,researchershavedevelopedcopper-catalyzedreactionsforthesynthesisofnaturalproductssuchasalkaloidsandterpenes,whichhaveawiderangeofbiologicalactivities.Copper-catalyzedcross-couplingreactionsarealsobeingusedtolinkbioactivemoleculestogethertocreatenovelcompoundswithimprovedpotencyandselectivity.

Finally,copper-catalyzedreactionsarebeingusedinthefieldofmaterialssciencetodevelopnewtypesofelectronicsandsensors.Copper-basedcompoundshavebeenshowntoexhibitinterestingelectronicandmagneticproperties,makingthempotentialcandidatesforuseinnext-generationelectronicdevices.Additionally,copper-catalyzedreactionsarebeingusedtocreatenewtypesofsensorsfordetectingarangeofsubstances,fromgasesandpollutantstobiologicalmolecules.

Inconclusion,copper-catalyzedreactionscontinuetobeanimportanttoolforsyntheticchemistsworkinginarangeoffields.Withongoingresearchintothedevelopmentandapplicationofcopper-basedcatalysts,itislikelythatwewillseefurtheradvancesinthesynthesisofnewmaterials,thedevelopmentofrenewableenergysources,drugdiscovery,andmaterialsscience.Inadditiontotheadvancesincopper-catalyzedreactions,therearealsosignificantdevelopmentsinthefieldofsensors.Sensorsaredevicesthatdetectandrespondtochangesintheenvironmentorphysicalconditions,suchastemperature,pressure,light,andthepresenceofchemicalsorbiologicalmolecules.Sensorsareusedinmanydifferentapplications,frommonitoringairqualityanddetectingtoxinsinfoodandwatertomeasuringglucoselevelsindiabeticpatientsandtrackingvitalsignsinhospitals.

Oneareaofresearchinsensorsisthedevelopmentofnewtypesofnanomaterialsthatcandetectandrespondtospecificmoleculesorcompounds.Nanomaterialsarematerialswithstructuresatthenanoscale,typicallybetween1and100nanometersinsize.Atthisscale,materialsoftenexhibitnovelproperties,suchasincreasedsurfacearea,enhancedreactivity,anduniqueelectronicoropticalproperties.

Oneexampleofananomaterial-basedsensoristheuseofcarbonnanotubestodetectdifferentgasesandpollutants.Carbonnanotubesarecylindricalstructuresmadeofcarbonatomsarrangedinauniquepattern.Theyarelightweight,strong,andhaveahighaspectratio,meaningtheyhaveahighratiooflengthtowidth.Thisuniquestructurealsomakesthemhighlysensitivetochangesintheenvironment,includingchangesintheconcentrationofdifferentgases.

Researchershavedevelopedcarbonnanotube-basedsensorsthatcandetectgasessuchascarbonmonoxide,nitrogendioxide,andhydrogensulfideatconcentrationsaslowaspartspermillion.Thesesensorsworkbyusingthecarbonnanotubesasasensingmaterialthatreactswiththegasmoleculesandchangestheelectricalresistanceofthenanotubes.Bymeasuringthechangesinresistance,researcherscandeterminetheconcentrationofthegasintheenvironment.

Anotherareaofresearchinsensorsisthedevelopmentofbiosensors,whicharesensorsthatcandetectbiologicalmoleculessuchasproteins,enzymes,andDNA.Biosensorshavemanyapplicationsinhealthcare,includingdiagnosingdiseases,monitoringdruglevelsinpatients,anddetectingpathogensinfoodandwater.

OneexampleofabiosensoristheuseofgrapheneoxidetodetectspecificDNAsequences.Grapheneisatwo-dimensionalmaterial