氰转化为酰胺

经典化学合成反应标准操作目 录1222323.1丙稀酰胺的合成23.2苯乙酰胺的合成3经典合成反应标准操作 —Mitsunobu 反应从氰基合成酰胺6.1氰基水解腈加水可以分解为伯酰胺。由于伯酰胺会继续水解为羧酸，一般要控制水解的条件。目前有许多方法报道，有时需要根据底物的特性选择酸性，碱性或中性的水解条件。作为中性的条件，也有文献报道使用镍或钯催化剂的方法。在酸性条件下与饱和碳相连的氰基，可以在酸中很方便的水解转化为酰胺，并在条件较为剧烈时，很容易进一步水解成酸。但乙烯基或芳基腈的水解条件则要求剧烈得多，一般需要强酸条件，而且一般不会进一步水解。在碱性条件下，利用过氧化氢氧化的方法可在室温下短时间内水解腈为伯酰胺，这是一个较为可靠的方法。利用NaOH(aq.)-CH2Cl2相转移催化体系，DMSO-K2CO3体系[2]可以用于各种腈水解为伯酰胺。6.1.1盐酸水解腈为伯酰胺示例 [3]HCl,H2OCN CONH2Ina3-l.three-neckedround-bottomedflaskequippedwithglassjointsareplaced200g.(1.71moles)ofbenzylcyanideand800ml.of35%hydrochloricacid.Theflaskisfittedwitharefluxcondenser,athermometer,andanefficientmechanicalstirrer.Atabathtemperatureofabout40the°mixtureisstirredvigorously. Withinaperiodof20–40minutesthebenzylcyanidegoesintosolution. Duringthistime,thetemperatureofthereactionmixturerisesabout10°abovethatofthebath.Thehomogeneoussolutioniskeptinthebathwith,orwithout,stirringforanadditional20–30minutes.Thewarmwaterinthebathisreplacedbytapwateratabout15–20°,andthethermometerisreplacedbyadroppingfunnelfromwhich800ml.ofcolddistilledwaterisaddedwithstirring. Aftertheadditionofabout100–150ml.,crystalsbegintoseparate.Whenthetotalamountofwaterhasbeenadded,themixtureiscooledexternallywithicewaterforabout30minutes. Thecooledmixtureisfilteredbysuction. Crudephenylacetamideremainsonthefilterandiswashedwithtwo100-ml.portionsof water. Thecrystalsarethendried at50–80°. The yield of crudephenylacetamideis190–200g.(82–86%).Page1of6经典合成反应标准操作 —Mitsunobu 反应6.1.2浓硫酸水解不饱和腈为伯酰胺示例 [4]1.H2SO4CN 2.NH3 CONH2To106gof84%sulfuricacid,wasadded50gofacrylonitrile.Afterstirringfor30minatr.t.,theresultingmixturewasheatedto95℃,andstirredfor2h.Aftercooling,thesolidwascollectedbysuction,andthefiltercakewastransferredintoabeaker.Totheice-cooledsolid,wasaddedaq.ammoniawiththespeedthatkeepthetemperaturelessthan℃50.Theprecipitatedammoniumsulphatewasfilteredoff,andthefiltratewascooled.Theprecipitatewascollectedbyfiltration,andthefiltercakewaswashedbywater,driedinvacuumtogivethedesiredproduct.6.1.3H2O2-K2CO3-DMSO体系水解腈为伯酰胺示例[1]30%H2O2,K2CO3OClCNClDMSO,rt,5minNH2Toastirredsolutionof4-chlorobenzonitrile(1.37g,0.01mol)inDMSO(3ml),cooledinaicebath,wasadded30%H2O2(1.2ml)andK2CO3,thereactionwasallowedtowarmuptor.t.(strongexothermiceffectwasobserved).After5min.,distilledwater(50ml)wasadded,coolingapplied,andtheproductwascollectedbyfiltration,yield85%.[2]6.1.4 NaOH(aq.)-CH2Cl2相转移催化体系水解腈为伯酰胺(n-C4H)N+HSO-9430%H2O2,CH2Cl2OCN20%NaOH,20-25℃NH2Toamagneticallystirreddichloromethanesolution(1.5ml)ofo-tolunitrile(0.5g,4.27mmol)cooledinanicebath,areadded30%hydrogenperoxide(2.0ml),tetrabutylammoniumhydrogensulfate(0.290g,0.85mmol),anda20%aqueoussolutionofsodiumhydroxide(1.6ml).ThePage2of6经典合成反应标准操作 —Mitsunobu 反应reactionmixtureisallowedtowarmuptor.t.andmaintainedunderstirring.After1.6h,dichloromethaneisadded,theorganiclayerisseparated,washedwithbrine,anddriedwithsodiumsulphate.Thesolventisremovedunderreducedpressuretoleaveawhitesolidfromwhichpureo-toluamideisobtainedbychromatographyonsilicagel.Yield0.485g(97%).6.2 Ritter反应碳正离子加成到腈基的氮原子上生成的腈盐加水分解得到相应的酰胺加水可以分解为酰胺。一般能产生碳正离子化合物都可以发生这类反应。由于醇或烯烃在浓硫酸或其他强酸加热条件下反应，一般在次条件下稳定的腈都可用于该类反应。这类反应通过腈和酸在溶剂中反应，但对于乙腈来说，直接用乙腈中反应即可，对于其他较为复杂，沸点较高的底物，一般用冰醋酸稀释。CH3CN,H2SO4CH3CNH2OOH3CCNNAcOH,20oC,overnight85%H一般卤代物用于这一反应比烯烃和醇要差，但用亚硝基四氟硼酸盐（ NOBF4）和亚硝基六氟磷酸盐(NOPF6)可以室温以下反应[5]。这两个试剂也可直接拔除三取代碳上的氢生成碳正离子。NOBF4,CH3CNOBr0oC-rt,1hNH当使用醇作反应物时，则可以得到相应的N-烃基酰胺[6]。MeOH(1.5eq),PPA(3.eq.)OCN150oC,10hNH而通过卤素或有机硒等对烯烃加成， 得到的碳正性的中间体也可用于对乙腈的加成[7]。如果所用的是环状烯烃，则为反式加成。PhSeCl,TfOH,H 2O SePhCH3CN,reflux,1h NHAcPage3of6经典合成反应标准操作 —Mitsunobu 反应6.2.1 Ritter反应示例一[8]H2SO4,AcOHH+NOHCN<40oC,1hOAsolutionof5.3g(0.1mol)ofacrylonitrile,50mlofaceticacidand7.4gof tbutylalcoholinanice-bathwastreatedwithconc.sulfuricacid(10.1g,0.1mol)withstirringsoastokeepthetemperaturebelow40℃duringtheadditionandsubsequentreaction(anhour),thereactionmixturewaspouredonto200gofice,theproductfilteredandairdried,yield10g(yield80%).Theproductcouldberecrystallizedfrombenzene.6.2.2 Ritter反应示例二[9]PhTMSCN,H2SO4PhPhOHPhNHCHOHOOCrt,18hCOOHToamixtureofalcohol(10mmol)andtrimethylsilylcyanide(20mmnol),cooledto-15Cinanice-saltbath,undernitrogen,isaddedconcentratedsulfuricacid(30mmol)dropwisewithvigorousstirring(caution:highlyexothermic).Aftertheaddition,thecoldbathisremovedandthemixtureisstiffedatambienttemperaturefor18hrs.Tilemixtureisthenpouredontoice,andneutralizedwith50%NaOHsolutiontopH=7.Theaqueousisextractedwitht-BuOMeorCHCl3,andthecombinedorganicextractsarewashedwithbrine,anddriedoverMgSO4.Thecrudeproductispurifiedbyrecrystallization(solid)orflashchromatography(oil).Reference：Synthesis1989,949Synthesis,1980,