伯酰胺转化为氰基

See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/260273495Dehydration of Amides to Nitriles: A ReviewArticle · January 2012CITATION1READS8,2741 author:Sangeeta JhaSikkim Manipal Institute of Technology29 PUBLICATIONS 63 CITATIONS SEE PROFILEAll content following this page was uploaded by Sangeeta Jha on 21 February 2014.The user has requested enhancement of the downloaded file.InternationalJournalofChemistryandApplications.ISSN0974-3111Volume4,Number4(2012),pp.295-304©InternationalResearchPublicationHousehttp://www.irphouse.comDehydrationofAmidestoNitriles:AReviewN.K.Bhattacharyya*,SatadruJha,SangeetaJha,TsheringYangdenBhutiaandGitaAdhikaryDepartmentofChemistry,SikkimManipalInstituteofTechnology,Majitar,Rangpo,Sikkim-737136,India*Email:nkamalbhatt@yahoo.comAbstractOverthepastfewdecadesstudiesondehydrationreactionofAmideshavebeenwelldocumentedintheliteratureandtheimportanceofNitrilesasintermediatesinOrganicSynthesisiswellestablished.ThisreviewfocusesonalltherecentsyntheticdevelopmentsinDehydrationofamidestoNitriles.Keywords:dehydration,amide,nitrile.Introduction:NitrilefunctionalitiesareextensivelyappliedinorganicSynthesisandusedfortheproductionofpharmaceuticals,agrochemicals,andpolymers1,2.Therefore,dehydrationofamidestonitrilesisanimportanttransformationinorganicsyntheses3,4,5.Nitrilesareoneofthemostimportantprecursorsinorganicsynthesis.Itmaybeusedasstartingmaterialforalargenumberofotherfunctionalgroupslikecarboxylicacid,amines,ketonesandalargenumberofmoleculesofcommercialsignificance6.Moreover,cyanogroupitselfispresentinHIVproteaseinhibitor7,5-lipoxygenaseinhibitors8andmanyotherbiologicalimportantmolecules9,10.Dehydrationisoneofthefundamentalmethodstoconvertprimaryamidestonitriles23.EarlierstrongacidicdehydratingagentslikeP2O524,POCl325,SOCl226,TiCl427,NaBH428etc.wereusedtoperformthistypeofreaction.Butpresently,anumberofefficientmethodshavebeenreportedforthedehydrationofamidestonitriles.DehydrationofAmidesinhydratedmedia3:Konwaret.al.developedafacilemethodofdehydrationofamidesinhydratedmedia.InthisprocessdehydrationofamideswerecarriedoutusingAlCl3.6H2O/KI/H2O/CH3CNsystem.296N.K.BhattacharyyaetalR-CO-NH2R-CNAlCl3.6H2O/KI/H2OReactionScheme(2.1)AmideswerereactedwiththeAlCl3.6H2O/KI/H2O/CH3CNsystem[1equivalentofAlCl3.6H2O/KI,1equivalentoftheamides]inamixtureofacetonitrileandwater(5:1)atrefluxtemperaturefor6handafterworkupwith5%ammoniumhydroxidesolution,itproducedcorrespondingnitrilesingoodyieldsinthehydratedmedia.Also,whenthesystemwastreatedwiththecyclicamides,intramolecularcyclodehydration(BischlerNaperialskireaction)occurred11andresultedindustriallyimportantisoquinolinederivatives.Zinc–CatalyzeddehydrationofPrimaryAmidestoNitriles1:StephanEnthaleret.al.developedthezinc-catalyzeddehydrationofamideswithN-methyl-N-(trimethylsilyl)trifluoroacetamide(MSTFA)asadehydrationreagentintothecorrespondingnitriles..Withthestraightforwardandcommerciallyavailablezinc(II)triflateastheprecatalystandMSTFA,anexcellentsystemhasbeenestablishedtoaffordnitrilesinexcellentyieldsandchemoselectivities.NH2OZn(1-5mol%)CNF3CNCH3SiMe3O(1-3.5equiv)ReactionScheme(2.2)ApressuretubewaschargedwithanappropriateamountofZn(OTf)2(0.05mmol,5.0mol%),thecorrespondingamide(1.0mmol),andMSTFA(3.5equivalents,3.5mmol).AfteradditionofTHF(2.0mL),thereactionmixturewasstirredinapreheatedoilbathat700Cfor24h.Themixturewascooledinanicebathandbiphenyl(internalstandard)wasadded.ThesolutionwasdilutedwithdichloromethaneandanaliquotwastakenforGC-analysis(30mRxi-5mscolumn,40–3000C).Thesolventwascarefullyremovedandtheresiduewaspurifiedbycolumnchromatography(n-hexane/ethylacetate5:1).DehydrationofPrimaryAmidestoNitrilesinSolventandSolvent-FreeConditions12:ONH2R(EtO)2POClR-CNTolueneorsolvent-freeheatReactionScheme(2.3)DehydrationofAmidestoNitriles:AReview297Primaryalkylandarylamidesefficientlyareconvertedtothecorrespondingnitrilesbyheatinginthepresenceofdiethylchlorophosphateinexcellentyields.Thismethodworksundermildconditionswithshorterreactiontimes.(MethodA):Foreachreaction,theamide(1mmol)andtoluene(1ml)waschargedintoa5mldouble-neckedround-bottomflaskequippedwithamagneticstirrerandcondenser.Themixturewasheatedtorefluxanddiethylchlorophosphate(1mmol)wasadded.Thereactionwasheatedfor5-20minandthenthereactionmixturewascooledtoroomtemperature.Thecrudemixturewasneutralizedby10mlaqueoussolutionofsodiumhydroxide(5%)andwasextractedbydiethylether(2×10ml).Dryingthecombinedethereallayerbyanhydroussodiumsulphateandthenfiltrationandevaporationofthesolventgavethecrudeproduct,whichwaspurifiedbyshortcolumnofsilicagelwithn-hexaneandethylacetate(9:1-1:1)togivethepureproduct.(MethodB):Foreachreaction,theamide(1mmol)waschargedintoa5mldouble-neckedround-bottomflaskequippedwithamagneticstirrerandcondenser.Thenthemixturewasheatedat120°Canddiethylchlorophosphate(1mmol)wasadded.Thereactionwasheatedfor5-25minandthenthereactionmixturewascooledtoroomtemperature.Themixturewasextractedbydiethylether(2×10ml).Thecombinedethereallayerwasallowedtodrybyanhydroussodiumsulphateandthenfiltrationandevaporationofthesolventgavethecrudeproduct,whichwaspurifiedbyshortcolumnofsilicagelwithn-hexaneandethylacetate(9:1-1:1)togivethepureproduct.Copper-CatalyzedDehydrationofPrimaryAmidestoNitriles13:StephanEnthaleret.al.introducedacoppercatalyzedprotocolforthedehydrationofprimaryamidestotheircorrespondingnitrilesapplyingN-methyl-N-(trimethylsilyl)trifluoroacetamide(MSTFA)assilylationreagent.NH2OF2.5mol%[Cu]CNF3CNCH3SiMe3O(3equiv)Toluene,1000C,24hReactionScheme(2.4)Apressuretubewaschargedwithanappropriateamountofcopper(I)chloride(0.018mmol,2.5mol%),andthecorrespondingamide(0.72mmol).Afteradditionoftoluene(2.0mL)2.0equivalentsofMSTFA(1.44mmol)wereaddedandthereactionmixturewasstirredinapreheatedoilbathat1000Cfor24h.Themixturewascooledtoroomtemperature.Thereactionmixturewasdissolvedindiethyletherandpurifiedbycolumnchromatographyafterthatthesolventswereremovedunderreducedpressure.DehydrationofPrimaryAmideswithPdCl2inAqueousAcetonitrile14:Anew,mild,andreversiblemethodtoconvertprimaryamidestonitrilesingoodyieldsusingPdCl2inaqueousacetonitrileisdescribedbySoniaI.Maffioliet.al.298N.K.BhattacharyyaetalR-CO-NH2R-CNcat.PdCl2inH2O-MeCNReactionScheme(2.5)PdCl2wastoconvertprimaryamidesintothecorrespondingnitrilesinaqueousorganicsolventsundermildconditions.ItwasreportedthatbyusingPdCl2inwater/acetonitrileassolventmixture,primaryamidesdehydratedingoodyieldsafterafewhoursatroomtemperature.Thereactiongavesatisfactoryresultsonbothaliphaticandaromaticprimaryamides,andinthelattercase,electronic-withdrawingor-donatinggroupsdidnotsignificantlyaffectthereactionrate.Thereactionwasshowntobereversible,andwaterwasfoundtobeformallytransferredfromthesubstratetotheacetonitrile.Aluminiumchlorideandsodiumiodide(AICI3-Nal):aversatiledehydratingagent15:AICI3-Nalisanefficientreagentfordehydrationofamidesanditformsisoquinolinederivativesbycyclodehydratingamidesinverygoodyieldsatroomtemperature.R-CO-NH2R-CNAlCl3/NaI,CH3CNReactionScheme(2.6)Anhydrousaluminiumchloride(0.264g,2mmol)andsodiumiodide(0.900gm,6mmol)wasaddedtodryacetonitrile(25ml)andthemixturestirredmagneticallyforhalfhouratroomtemperatureundernitrogen.Amide(1mmol)wasaddedandstirringwascontinuedunderrefluxforanother2.5h.TheprogressofthereactionwasmonitoredbyTLC.Thereactionmixturewaspouredintoicecoldammonicalwatersolution(10%)andextractedwithdiethylether.Theorganiclayerwaswashedwithwater(2x100mJ),driedandthesolventwasdistilledoffunderreducedpressuretogivenitrile.PreparationofnitrilesfromPrimaryAmidesunderSwernOxidationConditions16,19:R-CO-NH2R-CN(COCl)2-DMSOEt3NReactionScheme(2.7)NoriyukiNakajimaandMakotoUbukatareportedamildconversionmethodofprimaryamidestonitrilesusingtheactivateddimethylsulfoxide(DMSO)speciesundertheSwernoxidationconditions17,(COCl2)-DMSOandEt3N.DehydrationofAmidestoNitriles:AReview299Asolutionof(COC1)2(0.77mmol)inCH2C12(0.5mL)wasaddedtothesolutionofamide(0.55mmol)andDMSO(1.1mol)inCH2C12(1.5mL)at-780C.Afterstirringfor15min.at-78°C,Et3N(0.23mL,1.65mmol)wasaddeddropwisetothemixture.Afterthereactionmixturewasstirredfor15min.at-780C,themixturewasquenchedbyadditionofwater(5mL).Afterthismixturewaswarmedtoroomtemperature,theaqueouslayerwasextractedwithEtOAc(3x10mL).Thecombinedorganicphaseswerewashedwithbrine(30mL),dried(Na2SO4),andthenfiltered.(yield93%).RapidMethodofConvertingPrimaryAmidestoNitriles18:ArapidandfacilemethodfortheconversionofprimaryamidestonitrilesusinginexpensiveandreadilyavailableZnCl2inaqueousacetonitrileandtheirregenerationusingZnCl2–H2O–THFinthepresenceofacetamideundermicrowaveirradiationingoodyieldsisreported.Thereactioniscompletedby1min.NH2OCNZnCl2inH2O-MeCNReactionScheme(2.8)AmixtureofZnCl2(0.136g,1mmol)in1:1water/acetonitrile(1ml)wastakenintoaPyrexcylindricaltube;benzamide(0.121g,1mmol)wasthenadded.Themixturewashomogenizedandirradiatedinacommercialmicrowaveoven(320W).Attheendofirradiation(30s),themixturewascooledtoroomtemperatureandextractedwithdichloromethane(5ml).Theorganiclayerwasdriedoveranhydroussodiumsulphate,andthesolventwasremovedundervacuum.Thecrudeproductwaschromatographedonashortcolumnofsilicagelusing2.5%EtOAcinlightpetroleumaseluenttogetbenzonitrile(0.097g,94%).N-ProtectedChiralα-AminonitrilesfromN-Protecteds-AminoAcidAmides20,21:MarcRodriguezetal.reportedthedehrdrationofN-protectedα-amino-acidamidestoN-protectedα-aminonitrilesingoodyieldsandwithexcellentpuritiesbyreactionofthecorrespondingprimaryamideswithcyanuricchlorideinDMF.PG-NHNH2ORCyanuricchloride/DMFPG-NHCNRReactionScheme(2.9)ToastirredsolutionofaN-protectedα-amino-acidamide(10mmol.)in300N.K.Bhattacharyyaetaldimethylformamide(10ml)atroomtemperaturewasaddedatoncecyanuricchloride(Aldrich,922mg,5mmoi.).Uponcompletionofthereaction(monitoredbyTLC,generallynotmorethan30min.),water(c.a.100ml)wasadded.Whentheexpectedcompoundprecipitated,thesolidwascollectedbyfiltrationonasinteredglassfunnel,washedwith5%aqueoussodiumbicarbonate,thenwithwater,anddriedinvacuum.Whentheexpectedproductdidnotprecipitate,thereactionmixturewaspartitionedbetweenwaterandethylacetate,theorganiclayerwashedwith5%aqueoussodiumbicarbonate,thenwithwater,driedoversodiumsulfateandconcentratedunderreducedpressure.Theproductwasthencrystallizedfromtheappropriatesolvent.Catalyticpropertiesofironcomplexes:dehydrationofamidestonitriles22:MatthiasBelleretal.reportedvariousironcarbonylclusterssuchasFe2(CO)9or[Et3NH][HFe3(CO)11]tocatalyzethedehydrationofamidesintothecorrespondingnitrilesinthepresenceofsilanesinhighyields.Nagashimaandco-workers29reportedsimilartypeofreactionwithruthenium.CONH2Catalyst(EtO)2MeSiH(3.0equiv),toluene,1000CCNReactionScheme(2.10)Theyselectedbenzamidetobenzonitrilesasamodelsystemtoidentifyandoptimizecriticalreactionparameters.Here,(EtO)2MeSiHisusedasacomparablycheapandstablesilaneintolueneinthepresenceofvariousironcatalysts.Thereactiondidnotoccurintheabsenceofanycatalyst.However,toourdelight5mol%ofnon-toxiciron(II)acetatecatalyzedthedesiredtransformationandaffordedbenzonitrilein83%yield.Noreactionisobservedapplying5mol%ofeitherFe(CO)5,FeCl2orFeCl3.Ontheotherhand,higheractivitiesandgoodyields(83–92%)areobservedinthepresenceof2–3mol%of[CpFe(CO)2]2,Fe3(CO)12and[Et3NH][HFe3(CO)11].Nearlyquantitativeyield(97%)isobtainedapplyingFe2(CO)9.Otherironsources,suchasFe(acac)3,alsogavereasonableyieldofbenzonitrile.Supportedmonomericvanadiumcatalystfordehydrationofamidestoformnitriles30:KiyotomiKanedaetal.reportedthatMonomericvanadiumoxidespecieswhichiscreatedonthesurfaceofhydrotalcite(V/HT),actsasareusablesolidcatalystforthehighlyefficientdehydrationofamidesintothecorrespondingnitriles.DehydrationofAmidestoNitriles:AReview301CONH2CH3Catalystmesitylene,refluxCNCH3+H2Omesitylene,refluxRCONH2V/HTR-CN+H2OReactionScheme(2.11)Hydrotalcites(HTs,Mg6Al2(OH)16CO3)arelayeredanionicclaysconsistingofpositivelychargedtwo-dimensionalbrucitelayersandanionicspecies,suchashydroxideandcarbonate,locatedintheinterlayer.HTshaveattractedmuchattentionascatalystsbecauseoftheirmultifunctionality,includingtheircationandanionexchangeability,surfacetunablebasicityandmetaladsorptioncapacity31.SynthesisofV/HT:HT(1.0g)wasaddedto100mLofanaqueousVCl3solution(4mM)andthenthemixturewasstirredatroomtemperaturefor3h.Theobtainedslurrywasfiltered,washedwithdeionizedwateranddriedovernightatroomtemperatureinvacuotoyieldV/HT(V:1.9wt%)asapalegraypowder.DehydrationofAmidesbySilazanes,Chlorosilanes,Alkoxysilanes,andAminosilanes32:WilliamE.DennisreportedthedehydrationofamidestonitrileswiththehelpofSilazanes,aminosilanes,alkoxysilanes,andchlorosilanes.3RCONH2+(HNSiMe2)33RCN+3NH3+(OSiMe2)x(whereR=Me,Ph)4PhCONH2+(HNSiMe2)44PhCN+4NH3+(OSiMe2)xheatPhCONH2+(n-BuO)4SiPhCN+n-BuOCOPh+[(n-BuO)3Si]2OheatReactionScheme(2.12)CatalyticSynthesisofNitrilesfromAmides33:MatthiasBelleretal.reportedthefluoride-catalyzeddehydrationofamidestonitriles.Basicallytheyhighlightedthecatalyticdehydrationofaromaticandaliphaticamidesusingsilanesinthepresenceofcatalyticamountsoffluoride.Thesynthesisofaliphaticandaromaticnitrilesproceedswithhighselectivityundermildconditions.302N.K.BhattacharyyaetalCONH2TBAF(5mol%)CNhydrosilanesRCONH2RCNORORReactionScheme(2.13)Conversionofsubstitutedamidestonitriles34:Mahajanetal.reportedthesynthesisof2-amino–5-chlorobenzonitrilefrom2-amino-5-chlorobenzamideusingphosphorouspentoxide:CONH2NH2ClCNNH2ClP2O5-H2OReactionScheme(2.14)Phosphorouspentoxide(14mmoles)and2-amino-5-chlorobenzamide(6mmoles)weretakeninaroundbottonflask.Thereactionmixturewasshakenfor30minandthenvacuumdistilledfor1h.Thedistillatecontaining2-amino-5-chlorobenzonitrileandphosphoricacidwascollected.Itwasfilteredofftoseparatethesolidproduct,2-amino-5-chlorobenzonitrile,fromphosphoricacid.Itwaswashedwithcoldwaterandrecrystallizedfromaqueousethanol.Aconvenientnewprocedureforconvertingprimaryamidesintonitriles35:Anoperationallysimpleandhigh-yieldingprocedurehasbeendevelopedfortheconversionofprimaryamidestothecorrespondingnitriles,usingethyldichlorophosphate/DBUasthemilddehydratingagent.NH2OCNEthyldichlorophosphate/DBUReactionScheme(2.15)Procedure:Amide(1.0mmol)wastreatedwith3equivalentsofDBU(0.457g,3.0mmol)indichloromethane(5mL)atroomtemperaturefor10min,atwhichtime2equivalentsofethyldichlorophosphate(0.326g,2.0mmol)wasthenadded,andthereactionwascontinuedatthesametemperatureforadditional50min.AdditionofDehydrationofAmidestoNitriles:AReview303aqueousNH4Clfollowedbydichloromethaneextractionandflashchromatography(silicagel,10%ethylacetateinn-hexane)affordedthecorrespondingnitrile(98%).Whenthereactionwasrepeatedwithphenyldichlorophosphateinplaceofethyldichlorophosphate,97%yieldofthepureproductwasisolated.Conclusion:Thisarticlesummarizestherecentdevelopmentofdehydrationofamidestonitrilessincenitrilesfunctionalitiesareextremelyappliedinorganicsynthesis.Acknowledgement:WethanktheDirector,SikkimManipalInstituteofTechnology,Majitar,Rangpo,Sikkim(East)forprovidingresearchfacilities.References:[1]StephanEnthaler,andShigeyoshiInoue,2012,Chem.AsianJ,7,169–175.[2]R.C.Larock,2010,ComprehensiveOrganicTransformations,Wiley.[3]MonalisaBoruahandDilipKonwar,2002,J.Org.Chem.,67,7138-7139.[4]Konwar,D.;Boruah,R.C.;Sandhu,J.S,1990,TetrahedonLett.,34,1063-64andreferencestherein.[5]ComprehensiveOrganicTransformation,Aguidetofunctionalgrouppreparation;Larock,L.C.,Ed.,1989,VCH,Inc.:NewYork,pp991-993andreferencestherein.[6]A.Saini,SanjayKumar&JagirSSandhu,July2005,Ind.J.Chem,Vol44B,pp.1427-1429.[7]JanakiramanMN,WatenpaughKD,TomichPK,ChongKT&StrohbachJW,1998,BioorgMedChemLett,8,1237.[8]DubeD,BlovinM,BrideauC,TagariP&YoungRN,1998,BioorgMedChemLett,8,1255.[9]SerranoJL,SierraT,GonzalezY,BolmC,WeickhardtK,MagnusA&MoliG,1995,JAmChemSoc,117,8312.[10]ChihiroM,NagamotoH,TakemuraI,KitanoK,KomatsuH,SekiguchiK,TabuseF,MoriT,TomingaM&YabuuchiY,1995,JMedChem,38,353.[11]OrganicReactions,John-Wiley&Sons:London,1951,VolVI,pp.74-150.[12]Z.Shahsavari-FardandA.R.Sardarian,March2011,J.Iran.Chem.Soc.,Vol.8,No.1,pp.204-208.[13]StephanEnthaler,MaikWeidauer,2011,CatalLett,141:1079–1085.[14]SoniaI.Maffioli,EttoreMarzorati,andAlessandraMarazzi,2005,Org.Lett.,Vol.7,No.23,pp.5237–5239.[15]DilipKonwar,MonalisaBoruah,GautomKumarSarmah,NayanKamalBhattacharyya,NaleenBorthakur,BirendraNathGoswamiandKumarRanjanBoruah,2001,J.Chern.Research(5),490-492.304N.K.Bhattacharyyaetal[16]NoriyukiNakajimaandMakotoUbukata,1997,TetrahedronLetters,Vol.38,No.12,pp.2099-2102.[17](a)OmuraK.;SwernD.1978,Tetrahedron,34,1651.b)MancusoA.J.;HuangS-L.;SwernD.,1978,J.Org.Chem.,43,2480.c)Mancuso,A.J.;Swern,D.,1981,Synthesis,165.d)Sharma,A.K.;Ku,T.;Dawson,A.D.;Swern,D.,1975,J.Org.Chem.,40,2758.e)Verkey,T.E..;Whitfidd,G.F.;Swern,D.,1974,J.Org.Chem.,39,3365.f)Lee,T.V.InComprehensiveOrganicSynthesis,Oxidation;S.V.Ley,FRS,Ed.;1991,PergamonPress:Oxford,Vol.7.Chapter2.8.[18]K.ManjulaandM.A.Pasha;2007,SyntheticCommunicationsw,37:1545–1550.[19]NoriyukiNakajima,MihoSaitoandMakotoUbukata,2002,Tetrahedron58,3561-3577.[20]PhilippeMaetzandMarcRodriguez;1997,TetrahedronLetters,vol.38,No.24,pp.4221–4222.[21]Olah,G.A.,Narang,S.C.,Fung,A.P.andGupta,B.G.B.,1980,Synthesis,657-658.[22]ShaolinZhou,DanieleAddis,ShoubhikDas,KathrinJungeandMatthiasBeller,2009,Chem.Commun.,4883–4885.[23](a)R.E.KentandS.M.McElvain,1945,Org.Synth.,25,61.(b)D.T.Mowry,1948,Chem.Rev.,42,189.[24]D.B.ReisnerandE.C.Horning,1963,Org.Synth.,Coll.IV,144.[25]B.RickbornandF.R.Jensen,1962,J.Org.Chem.,27,4608.[26]J.A.KrynitskyandH.WCarhart,1963,Org.Synth.,Coll.IV,436.[27]W.Lehnert,1971,TetrahedronLett.,19,1501.[28]S.E.Ellzey,C.H.MackandW.J.Connick,1967,J.Org.Chem.,32,846.[29]S.Hanada,Y.MotoyamaandH.Nagashima,Eur.,2008,J.Org.Chem.,24,4097.[30]ShoichiroSueoka,TakatoMitsudome,TomooMizugaki,KoichiroJitsukawaandKiyotomiKaneda,2010,Chem.Commun.,46,8243–8245.[31]A.Vaccari,Catal.1991,Today,11,173.[32]WilliamE.Dennis,1970,J.Org.Chem.,Vol.36,No.10,3253.[33]ShaolinZhou,KathrinJunge,DanieleAddis,ShoubhikDas,andMatthiasBeller,2009,OrganicLetters,Vol.11,No.11,2461-2464.[34]S.S.Mahajan&A.Mahalakshmi,May2006,IndJ.Chem,Vol.45B,pp.1299-1300.[35]Chun-WeiKuo,Jia-LiangZhu,Jen-DarWu,Cheng-MingChu,Ching-FaYaoandKak-ShanShia,2007,Chem.Commun.,301–303.Viewpublicationstats