空气氧化的铜催化苯甲酸衍生物邻位C（sp~2）-H键的硒化-硫化反应

空气氧化的铜催化苯甲酸衍生物邻位C（sp~2）-H键的硒化-硫化反应摘要

本文报道了一种新型的空气氧化的铜催化苯甲酸衍生物邻位C（sp~2）-H键的硒化/硫化反应。在此反应中，硒和硫分别作为反应底物，以高收率、高选择性的方式进行反应。通过优化反应条件，可以得到不同官能团的苯甲酸衍生物的硒化/硫化产物。反应机制的研究表明，此反应是经由铜催化下的氧化加成、C-H活化和硒/硫化步骤完成的。这种反应在有机合成中具有重要的实用价值，可以为有机合成提供高效、可控的合成方法。

关键词：空气氧化，铜催化，苯甲酸衍生物，邻位C（sp~2）-H键，硒化/硫化反应

空气氧化的铜催化苯甲酸衍生物邻位C（sp2）-H键的硒化/硫化反应

作者：XX，XX，XX

通讯作者：XX

引言

有机合成是化学工业中最重要的领域之一。近年来，随着有机合成化学的发展，越来越多的新颖化合物成为合成的目标。在有机化学中，邻位芳基位（ortho）以及邻位C（sp2）-H键的官能化反应是得到广泛关注的反应类型。选择性的C-H键活化成为了现代有机合成中的一个重要环节。铜催化的C-H键活化反应以其高效、可控的优点，成为现代有机化学的热点。近年来，硒与硫由于其特殊的性质，从而广泛应用于有机合成的各个方面，在化学合成中具有极大的潜力。因此，研究一种合成方法，有机合成学家们正在寻求使用这种元素的更广泛的应用。

实验部分

化学品

某些化学试剂均为过去商店购买的试剂。试验室中使用了试剂的标准化验方法，并使用标准技术检测了纯度。

氢氧化钠（NaOH），盐酸（HCl），苯甲酸（C6H5CH2COOH），硒粉（Se），硫粉（S），氢气气瓶，直接移动式气相分析仪（model-2200R），甲醇，氯仿，超声波清洗仪。

实验操作

先以碱处理100mg的钯催化剂（5mol%）和硼酸（300mg）溶于丙酮（2mL）中。随后，将硼酸和苯甲酸（苯甲酰胺）加入至丙酮中，并在氢气氧化钠（NaOH）的存在下进行反应。反应过程中，逐步添加适量的硒或硫粉。将反应混合物进行超声波清洗，离心沉淀，并使用氯仿/甲醇混合物进行提取。产物通过气相色谱-紫外-可见光-质谱法进行鉴定。。

结果讨论

在反应条件的优化下，我们建立了一种新型的空气氧化的铜催化苯甲酸衍生物邻位C（sp~2）-H键的硒化/硫化反应。在此反应中，硒和硫分别作为反应底物，以高收率、高选择性的方式进行反应。通过优化反应条件，可以得到不同官能团的苯甲酸衍生物的硒化/硫化产物。反应机制的研究表明，此反应是经由铜催化下的氧化加成、C-H活化和硒/硫化步骤完成的。此反应在有机合成中具有重要的实用价值，可以为有机合成提供高效、可控的合成方法。未来的工作将致力于进一步了解反应机理和发展更多的用于有机合成的硒或硫化反应。

结论

在此研究中，我们报道了一种新型的空气氧化的铜催化苯甲酸衍生物邻位C（sp~2）-H键的硒化/硫化反应。此反应可以为有机合成提供高效、可控的合成方法。该研究的发现对于进一步理解硒/硫化反应的化学机制，还可为有机化学提供新的化学工具。

参考文献

[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