实验十七苯片呐醇的制备及

实验十七苯片呐醇的制备一、实验目的1、学习苯环支链上的氧化反应2、掌握减压过滤和重结晶提纯的方法

二、实验原理三、实验仪器和药品天平、量筒、圆底烧瓶、冷凝管、电炉、布氏漏斗、抽滤瓶、甲苯、高锰酸钾、浓盐酸、沸石、活性炭

四、实验步骤1、在烧瓶中放入2.7ml甲苯和100ml蒸馏水，瓶口装上冷凝管，加热知沸腾。经冷凝管上口分批加入8.5g高锰酸钾。黏附在冷凝管内壁的高锰酸钾用25ml水冲入烧瓶中，继续煮沸至甲苯层消失，回流液中不再出现油珠为止。2、反应混合物趁热过滤，用少量热水洗涤滤渣，合并滤液和洗涤液，并放入冷水浴中冷却，然后用浓盐酸酸化至苯甲酸全部析出为止（若滤液呈紫色加入亚硫酸氢钠除去）。3、将所得滤液用布氏漏斗过滤，所得晶体置于沸水中充分溶解（若有颜色加入活性炭除去），然后趁热过滤除去不溶杂质，滤液置于冰水浴中重结晶抽滤，压干后称重。回流装置图

五、实验数据处理

六、思考题反应完毕后，若滤液呈紫色。加入亚硫酸氢钠有何作用？亚硫酸氢钠可以和高锰酸钾反应，消耗多余的高锰酸钾，生成二氧化锰，溶液紫色褪去，产生棕色沉淀。简述重结晶的操作过程选择溶剂→溶解固体→除去杂质→晶体析出→晶体的收集与洗涤→晶体的干燥①将待重结晶的物质溶解在合适的溶剂中，制成过饱和溶液。②若待重结晶物质含有色杂质，可加活性碳煮沸脱色。③趁热过滤以除去不溶物质及活性碳。④冷却滤液，使晶体从过饱和溶液中析出，而可溶性杂质仍保留在溶液里。⑤减压过滤，把晶体从母液中分离出来，洗涤晶体以除去吸附在晶体表面上的母液。在制备苯甲酸过程中，加料高锰酸钾时，如何避免瓶口附着？实验完毕后，粘附在瓶壁上的黑色固体物是什么？如何除去？答：可借助粗颈漏斗或将称量纸叠成喇叭状将研细的固体物体加入瓶中。粘附在壁上的黑色固体物为二氧化锰，简单的除去方法为：加入稀的亚硫酸钠溶液，轻轻震荡可除去二氧化锰，其原理为氧化还原机理。

七、注意：一定要等反应液沸腾后（高锰酸钾只溶于水不溶于有机溶剂），高锰酸钾分批加入，避免反应激烈从回流管上端喷出。在苯甲酸的制备中，抽滤得到的滤液呈紫色是由于里面还有高锰酸钾，可加入亚硫酸氢钠将其除去。真题再现现有甲苯用高锰酸钾氧化制得的粗苯甲酸5g，其中含有少量杂质，并带有颜色。通常情况下苯甲酸为白色晶体,密度1.27，mp122℃，微溶于冷水，溶于沸水，乙醇，乙醚，氯仿，苯等溶剂。请用重结晶方法提纯苯甲酸，叙述操作过程。（北京理工大学2006年）（1）取5g粗苯甲酸,放入150mL锥形瓶中，加入一定量的水，石棉网上加热至沸腾,等固体完全溶解。若有尚未完全溶解的固体，可继续加入少量热水，每次少量，直至完全溶解后,再多加2~3mL水，移去火源，稍冷后加入少许活性炭,稍加搅拌后继续加热5～10min。（2）安装好预热过的抽滤转装置,将上述热溶液趁热抽滤,滤液倒入干净的烧杯中,慢慢冷却至室温,待晶体完全析出后,再进行抽滤,用少量水洗涤漏斗中的晶体,用玻璃塞挤压晶体,直至抽干。取出晶体,放在培养皿中摊开晾干或用红外灯烘干,称重计算收率。

实验十五、十六二苯甲醇的制备二苯甲醇，常温下白色至浅米色结晶固体，熔点69℃。易溶于乙醇、醚、氯仿和二硫化碳，几乎不溶于冷的粗汽油，20℃水中溶解度仅为0.5g/L。低毒，缺乏有关毒性数据，可参照甲醇毒性，避免与皮肤和眼睛接触。明火、高温、遇强氧化剂可着火燃烧，释放出有毒气体。

二苯甲醇主要用于有机合成，医药工业中间体。可作为抗过敏药物苯海拉明、帕金森药物苯甲托品的中间体。二苯甲醇用还原二苯甲酮的方法制备，还原方法有很多种，实验室常用的有硼氢化钠还原及碱性条件下以锌粉还原。方法一硼氢化钠还原法该法属于金属氢化物还原，由金属氢化物提供负氢离子还原羰基。类似的金属氢化物还有氢化铝锂、三叔丁氧基氢化铝锂；硼氢化钠，性质温和，可在水或醇溶液中反应；选择性高，不还原双键、三键，一般也不还原酯，酰胺，羧酸及腈。方法二锌粉还原法该法是活泼金属单分子还原法，底物接受金属一个电子生成负离子自由基，再接受一个电子生成二价负离子，最后与质子结合生成醇。金属还可选择钠、锂、镁、铁、锡等。锌的还原性和价格都适中，反应条件温和，后处理简单。两种方法的具体操作稍有不同，详细过程如下：方法一在装有回流冷凝管的25毫升圆底烧瓶中，加入1.83克二苯甲酮和8毫升甲醇，摇动使其溶解，迅速称取0.23克硼氢化钠加入瓶中，摇动使之溶解；反应物自然升温至沸腾，室温下放置20分钟，不时振荡，入3毫升水，加热至沸，保持5分钟；冷却，析出结晶。抽滤，粗品干燥后以石油醚重结晶，干燥后得白色针状晶体，称重，计算收率，测熔点。方法二在装有冷凝管和搅拌磁子的50毫升烧瓶中，依次加入2.0克氢氧化钠、1.83克二苯甲酮、2克锌粉、20毫升95%乙醇，充分振荡，使氢氧化钠和二苯甲酮逐渐溶解。反应微放热，约20分钟后，以80℃温度加热搅拌2小时；反应物冷却后，抽滤，固体以少量乙醇洗涤，滤液倒入80毫升事先用冰水冷却的水中，摇荡混匀后以浓盐酸小心酸化，使pH=5~6，抽滤；粗产物干燥后，以15毫升石油醚重结晶，得针状晶体，干燥，称重，计算收率，测熔点。实验过程中，请大家注意以下事项：硼氢化钠有一定腐蚀性，称量时小心操作，不要接触皮肤，也不要吸入颗粒或粉末；二苯甲醇粗品应干燥彻底后再进行重结晶，否则水分会影响重结晶过程；酸化时溶液酸性不宜太强，否则晶体难以析出。

等离子体电化学通过片纳醇偶联形成碳-碳键醛酮片醇偶联形成碳-碳键需要较大的负还原电位，通常用化学计量还原试剂来实现。在这里，我们使用通过等离子液相过程产生的溶剂化电子。对甲基-4-甲酰基苯甲酸酯的参数研究表明，在竞争还原成酒精的选择性需要对质量运输的小心控制。这种通用性在苯甲醛、苯酮和糠醛中得到了证明。反应扩散模型解释了观察到的动力学，从头计算提供了对机理的洞察力。这项研究为还原有机反应提供了一种无金属、电力、可持续的方法。图1。实验产率(红方框)和模型结果(虚线)在MFB等离子-液体过程中得到的片纳醇产品作为(a)反应时间和(B)电流的函数。MFB初始浓度为0.12M，电流为2.3mA，反应时间为4h，甲醇(MeOH)与水的体积比为5:1。用核磁共振氢谱测定产率。误差条代表了六个独立试验的标准差。图2。(A)MFB的摩尔转化率随初始MFB浓度的变化;(B)产物产率与甲醇/水体积比的关系;(C)片那醇产品的法拉第效率随初始MFB浓度的变化;(D)片呐醇产物的法拉第效率随甲醇/水体积比的变化。Pinacol=红色，缩醛=蓝色，酒精=粉红色，酸=紫色。MFB初始浓度为0.12M，电流为2.3mA，反应时间为4h，除另有说明外，meoh与水的体积比为5:1。图3。采用复合相关G3(MP2)B351方法，采用DFT//M06/DZVP2等配线法计算MFB片纳醇偶联中间体的自由能面。自由基二聚(红色)和自由基加成(蓝色)途径显示。方案一。等离子体介导的片纳醇偶联的范围总之，我们证明了等离子体-液体过程中产生的溶剂化电子能够通过片呐醇偶联反应形成碳-碳键。模型底物(MFB)的参数研究表明，通过解决质量运输限制，对竞争酒精的选择性是可以实现的。该方法的通用性延伸到其他对取代苯甲醛、芳酮和糠醛，产率接近40%。据我们所知，这是等离子体产生的溶剂化电子用于有机氧化还原耦合反应的第一个例子，并为类似的还原有机反应提供了一个可持续的解决方案。

经典化学合成反应标准操作-醇的制备1.

羧酸酯还原为醇1.1金属钠和醇为还原剂Thecentralneckofa5-l.three-neckedround-bottomedflaskisfittedwithastoppercarryingamercury-sealedmechanicalstirrer.Oneofthesidenecksisconnectedbymeansofashortpieceofheavyrubbertubingtoalargerefluxcondenserabout2m.long,withaninnertube2.5cm.indiameter.Thethirdneckisfittedwithaseparatoryfunnel.Intheflaskareplaced70g.(3moles)ofsodiumand200cc.ofdrytoluene.Theflaskisheatedinanoilbathuntilthesodiumismelted.Thestirreristhenstarted;whenthesodiumisfinelydivided,theoilbathisremovedandthemixtureallowedtocool.Stirringmustbecontinuedduringthecoolinginordertokeepthesodiumfinelydivided.Whenthemixturehascooledtoabout60°,thereareaddedfromtheseparatoryfunnel,first,asolutionof114g.(0.5mole)ofethyllauratein150cc.ofabsolutealcohol,then500cc.moreofalcohol,asrapidlyasispossiblewithoutlossofmaterialthroughthecondenser.Thetimerequiredfortheadditionoftheestersolutionandthealcoholislessthanfiveminutes,usuallytwoorthreeminutes.Whenthereactionhassubsided,theflaskisheatedonasteambathuntilthesodiumiscompletelydissolved.Themixtureisthensteam-distilledtoremovethetolueneandethylalcohol.Thecontentsoftheflaskaretransferredtoaseparatoryfunnelwhilestillhotandwashedthreetimeswith200-cc.portionsofhotwatertoremovethesodiumlaurate.Thelaurylalcoholisextractedwithetherfromthecooledmixtureandthewashings.Thecombinedetherextractsarewashedwithwater,sodiumcarbonatesolution,andagainwithwater,anddriedoveranhydrousmagnesiumsulfate.Theetherisevaporatedandthelaurylalcoholdistilledunderdiminishedpressure.Theyieldis60–70g.(65–75percentofthetheoreticalamount)ofaproductboilingat143–146°/18mm.or198–200°/135mm.1.2金属氢化物为还原剂Adry,500-mL,three-necked,round-bottomedflaskisequippedwitha150-mLpressure-equalizingadditionfunnel,arefluxcondensertoppedwithaninertatmosphereline,aglassstopper,andanegg-shapedmagneticstirringbar.Theflaskischargedwithlithiumaluminumhydride(2.66g,0.070mol)andanhydrousether(50mL).Theflaskiscooledto5°Cinanice-waterbath.Asolutionofcycloadduct

2

(22.4g,0.072mol)inether(80mL)istransferredtotheadditionfunnelandaddedovera30-minperiod.Thereactionmixtureisstirredforanother15min,dilutedwithether(100mL),andquenchedbydropwiseadditionofwater(9mL).Theice-waterbathisremoved,theresultinggraysuspensionisallowedtoreachroomtemperature,andthemixtureisstirredvigorouslyforanadditional60min.Themixtureistransferredtoa1.0-LErlenmeyerflaskanddilutedwith350mLofether.Anhydroussodiumsulfate(Na2SO4)(60g)isadded,thesuspensionisstirredfor30min,andfiltered.Thefiltercakeiswashedtwicewithether(50mLeachtime).Thesolventisremovedonarotaryevaporatorandtheremainingvolatilematerialisremovedunderhighvacuumtoafford18.6g(91%)ofthedesiredaminoalcoholasaviscousclearoil.2.

羧酸还原为醇2.1LAH和硼烷还原羧酸Anoven-dried,3-L,three-neckedflaskequippedwithamechanicalstirrer,aFriedrichcondenser,andanitrogen-inlettubeisflushedwithnitrogen,andthenchargedwithasuspensionoflithiumaluminumhydride(47.9g,1.26mol)in1200mLoftetrahydrofuran(THF).Themixtureiscooled(10°C,icebath)andL-valine(100g,0.85mol)isaddedinportionsovera30-minperiodfroma200-mLround-bottomedflaskconnectedtothereactionflaskviaaflexibleplasticsleevesoasnottoproducetoovigorousanevolutionofhydrogen.Aftertheadditioniscomplete,theplasticsleeveisreplacedbyastopper,theicebathisremoved,andthereactionmixtureiswarmedtoroomtemperatureandthenrefluxedfor16hr.Thereactionmixtureisthencooledagain(10°C,icebath)anddilutedwithethylether(1000mL).Thereactionisquenchedovera30-minperiodwithwater(47mL),aqueous15%sodiumhydroxide(47mL,over20min),andwater(141mL,over30min).Thesolutionisstirredfor30minandthewhiteprecipitateisfiltered.Thefiltercakeiswashedwithethylether(3×150mL)andtheorganicfiltratesarecombined,driedwithanhydroussodiumsulfate,andconcentratedunderreducedpressure.DistillationoftheresidueundervacuumaffordsL-valinol(63.9–65.7g,73–75%)(Note5)asaclearliquid:bp63–65°C(0.9mm)(Note6):[α]D+14.6°(neat);

nD1.455;IR(neat)cm1:3300,1590;1HNMR(CDCl3)δ:0.92(d,6H),2.38–2.74(m,4H),3.13–3.78(m,2H).A2-L,three-necked,round-bottomedflaskisequippedwithamechanicalstirrer,heatingmantel,250-mLgraduatedadditionfunnel,andan8-in.,air-cooledrefluxcondenser(Westtype)toppedwithawater-cooleddistillationheadanda1-Lreceivingflask.Itisconnectedtoanitrogenlinethroughthestillhead.Theglasswareiseitheroven-driedandcooledinadesiccatororflame-driedandassembledwhilestillhot.Theassemblyisflushedwithnitrogenandchargedwith200gofL-valine(1.7mol),400mLoftetrahydrofuran(THF),and210mLoffreshlydistilledborontrifluorideetherate(242g,1.7mol).ThemixtureisheatedataratesufficienttocausetheTHFtorefluxgentlyand188mL(1.88mol)ofborane–methylsulfidecomplex(BMS)isaddeddropwiseoverthecourseof2hr.Thesolutionisthenrefluxedfor18hr.Themethylsulfidethathascollectedatthedstillheadisdiscarded,andthereactionmixtureiscooledto0°Candquenchedbytheslowadditionof200mLofmethanol.Theadditionfunnelisreplacedbyaglassstopper,andtheair-cooledcondenserisremoved,leavingtheflaskequippedfordistillationofsolventthroughthedistillationhead.Thereactionmixtureisconcentratedunderreducedpressurewithheatingandstirring.Thedistillationheadisreplacedbyawater-cooledrefluxcondenser,andtheresidueisdissolvedin1Lof6

M

sodiumhydroxideandrefluxedfor4hr.Themixtureissaturatedwithpotassiumcarbonate(ca.400g);cooled;filteredthroughaCelitepadonacoarse,frittedfunnel;andextractedwiththree1-Lportionsofchloroform.Thecombinedextractsarewashedwiththreeportionsofsaturatedsodiumchloride(5002020mLeach),stirredoveranhydrouspotassiumcarbonatefor24hr,andconcentratedunderreducedpressuretogiveayellowoil.Thecrudematerialisvacuumdistilledtogive77.5g(44%)ofpurifiedLvalinol,bp62–67°C/2.5mm;[α]D+14.6°(neat),

nD1.455;IR(neatfilm)cm−1:3300(OH),and1590(NH2);NMRδ:0.92(d,6H),1.54(m,1H),2.38–2.74(m,4H),3.13–3.78(m,2H).2.2

硼烷还原不饱和酸Adry,2-L,one-necked,round-bottomedflaskisequippedwitha1-Lpressure-equalizingfunnelandalargemagneticstirringbar.Thesystemisflame-driedunderaninternalatmosphereofdrynitrogen.Theflaskischargedwith300mLofanhydroustetrahydrofuranand100gofmonoethylfumarate.Thesolutionisthenstirredundernitrogenandbroughttoabout−5°Cusinganice–salt/methanolbath(−10°C).A1

M

solutionof700mL(0.70mol)ofborane–tetrahydrofurancomplexis

cautiously

addeddropwise(rapidH2evolutionoccurs)withrigoroustemperaturecontroltoavoidanexothermicreaction.Theice–saltbathismaintainedinpositionthroughoutthe90minofaddition.Thestirredreactionmixtureisthengraduallyallowedtowarmtoroomtemperatureoverthenext8–10hr.Thereactioniscarefullyquenchedatroomtemperaturebydropwiseadditionof1:1water:aceticacid(ca.20mL)withstirringuntilnomoregasevolutionoccurs.Thereactionisconcentratedatroomtemperatureandwaterpumppressuretoaslurrybyremovalofmostofthetetrahydrofuran.Theslurryiscarefullypouredovera20-minperiodinto300mLofice-cold,saturatedsodiumbicarbonatesolutionwithmechanicalstirringtoavoidprecipitationofsolids,andtheproductisextractedwith300mLofethylacetate.Theaqueouslayerisagainextractedwith100mLofethylacetate.Theorganiclayersarecombined,washedoncewith200mLofsaturatedsodiumbicarbonate,thendriedwellwithanhydrousmagnesiumsulfate.Solventremovalatreducedpressuregives61g(67%yield)ofessentiallypureethylhydroxycrotonate.Ananalyticalsamplemaybepreparedbyquickdistillation(orKugelrohrdistillation)at117–120°C(15mm),butthereissignificantlossofmaterialbecauseofdecompositioninthedistillationpot.From1gofproduct,0.72gofpurematerialisobtainedinthisway,andrecoverydecreasesasscaleofdistillationincreases.3.醛和酮还原成醇3.1.醛和酮还原的加氢还原Ina2-l.three-neckedflaskequippedwithastirrerandthermometerareplaced336g.(2.62moles)of3,4-dihydro-2-methoxy-4-methyl-2H-pyran(p.311),630ml.ofwater,and24ml.ofconcentratedhydrochloricacid(sp.gr.1.19).Themixtureisstirredfor2hours,duringwhichthetemperaturemayreach50°butshouldnotbepermittedtorisehigher.SolidsodiumbicarbonateisthenaddeduntilthesolutionisneutraltopHindicatorpaper(Note1).Theentirereactionmixtureweighingabout1kg.togetherwith39g.ofRaneynickel2isintroducedintoa3-l.stainless-steelrockinghydrogenationautoclave.Ahydrogenpressureofatleast1625p.s.i.(Note2)isapplied,andtheautoclaveisheatedto125°andheldtherewithshakingfor4hours.Themixtureisallowedtocoolovernight,andthecatalystisseparatedeitherbysuctionfiltrationthroughFilter-Celorbycentrifugation.Thesolutionisdistilledthrougha12-in.Vigreuxcolumn.Afterthemethanolandwaterareseparated,the3-methyl-1,5-pentanedioldistilsat139–146°/17mm.,149–150°/25mm.Theyieldis251–256g.(81–83%),

n25，1.4512–1.4521.3.2金属还原3.2.1Na-NH3体系A5-L,three-necked,round-bottomedflaskisequippedwithavariablespeedHershbergstirreranda500-mLDewarcondenserfilledwithdryice–acetoneandconnectedbyitsupperjointtoamineraloilbubblerthroughwhichpassesdrynitrogengas.Theflaskisimmersedinadryice–acetonebath,flushedwellwithnitrogenand3000mLofammoniaiscondensedintotheflaskviaaglasstubepassedthrougharubberseptumintheremainingneckoftheflask.Cleansodium,125g(5.43g-atom),isaddedslowlytotheammoniawithslowstirring.Then250.3g(0.906mol)of5-methyl-2-[1-methyl-1-(phenylmethylthio)ethyl]cyclohexanoneand72.5mL(1.8mol)ofmethanolin625mLofanhydrousetherareaddeddropwiseviaapressure-equalizedadditionfunnelover5hrtothevigorouslystirred(ca.500rpm)solution.Stirringiscontinuedanadditional30minfollowingwhich150mLofmethanolisaddedover2.5hrdropwise(toavoidaviolenteruption).Thesolutionisallowedtowarmslowlyandtheadditionfunnelandthecondenserareremovedtoallowtheammoniatoevaporateovernight.Thereactionflaskisimmersedinanicebathand700mLofwaterisaddedcautiouslyoveranhourtotheyellowsolidleftbyevaporationoftheammonia.Thesolutionistransferredtoa2-Lseparatoryfunnelandextractedwithtwo200-mLportionsofether,whicharediscarded.Theaqueouslayerispouredintoamixtureof500mLofconcentratedhydrochloricacidand1000gofice,transferredtoa4-Lseparatoryfunnel,andextractedwithfour200-mLportionsofether.Thecombinedetherextractsarewashedwith200mLofwaterand200mLofsaturatedaqueoussodiumchloride,driedovermagnesiumsulfate,andconcentratedbyrotaryevaporationataspiratorvacuum.Theresidualliquidisplacedunderreducedpressure(0.2mm)for1hrtoremovetheremainingsolventtogive137–140g(80–82%)ofanorangeoilthatisadiastereomericmixtureofwhichthemajorcomponentconstitutes80%,asindicatedby13CNMR.3.2.2Na-EtOH体系Ina3-l.round-bottomedflask,fittedwithanefficientLiebigcondenser(100by1cm.),228g.(2moles)ofmethyl

n-amylketoneisdissolvedinamixtureof600cc.of95percentalcoholand200cc.ofwater.Onehundredthirtygrams(5.6gramatoms)ofsodiumintheformofwireisgraduallyaddedthroughthecondenser.Duringtheadditionofthesodiumtheflaskiscooledwithrunningwater

sothatthereactiondoesnotbecomeundulyviolent.Whenthesodiumhasdissolved,2l.ofwaterisaddedandthemixtureiscooledto15°.Theupperoilylayeristhenseparated,washedwith50cc.of1:1hydrochloricacidandthenwith50cc.ofwater,driedover20g.ofanhydroussodiumsulfate,anddistilledwithafractionatingcolumn.Afterasmallfore-runoflow-boilingliquid,thepureheptanoldistilsat155–157.5°.Theyieldis145–150g.(62–65percentofthetheoreticalamount).3.2.3Na(Hg)

体系Anamalgampreparedfrom9.0g.(0.39atom)ofsodiumand750g.(55cc.)ofmercury(Note1)iswarmedtoabout50°(Note2)ina500-cc.Pyrexround-bottomedflask(Note3).Toitisthenaddedacoldsuspensionof25g.(0.13mole)ofxanthone(p.552)in175cc.of95percentethylalcohol.Theflaskisatoncestoppered,heldinacloth,andvigorouslyshaken,thestopperbeingraisedfromtimetotimetoreleaseanypressure.Thetemperaturerisesrapidlyto60–70°.Thesolidxanthonerapidlygoesintosolution,averyfaintandtransientbluecolorbeingdeveloped.Attheendofaboutfiveminutesthealcoholicsolutionisclearandpracticallycolorless.Afterafurtherten-minuteshakingthemercuryisseparatedandwashedwith10–15cc.ofalcohol.Thealcoholicsolutionisfilteredwhilewarmandslowlypouredwithstirringinto2l.ofcolddistilledwater.Theprecipitatedxanthydrolisfilteredwithsuction,washedwithwateruntilfreeofalkali,anddriedat40–50°toconstantweight.Thecrystallineproduct,whichweighs23–24g.(91–95percentofthetheoreticalamount),meltsat121–123°andispracticallypure(Note4)and(Note5).3.2.4Fe-HOAc体系Ina12-l.flaskfittedwithamechanicalstirrerandashortrefluxcondenserareplaced1800g.(32.2atoms)ofironfilings,3l.(52.5moles)ofglacialaceticacid,3l.ofwater,and450g.(3.95moles)ofheptaldehyde.Themixtureisheatedonthesteambath,withstirring,forsixtosevenhours.Theflaskisthenfittedtoanapparatusforsteamdistillation(p.479)andthemixturedistilledinacurrentofsteamuntilnomoreoilpassesover(7–8l.ofdistillate).Theoilisthenseparated,andtheaqueouspartdistilledtorecoverasmallquantityofdissolvedorsuspendedheptylalcohol.Thecombinedproductismixedwith1l.of20percentsodiumhydroxidesolutionandstirredonthesteambathforfourhours,inordertohydrolyzeasmallproportionofheptylacetate.Theoilisthenseparatedanddistilled,andtheportionboilingat172–176°iscollected.Theresidueintheflaskismixedwithabout100cc.ofwateranddistilled,whereuponafurthersmallquantityofoilpassesoverwiththesteam.Thisdistillateandtheforerunarefreedofthebulkofthewaterinaseparatoryfunnelanddistilledfromasmallerflask.Inthiswaythetotalyieldof

n-heptylalcoholboilingat172–176°(uncorr.)is350–370g.(75–81percentofthetheoreticalamount).Thealcoholmayberedistilledunderreducedpressure,whenitpassesoveralmostwithoutlossat71–72°/12mm.3.2.5Zn-EtOH体系Ina3-l.round-bottomedflaskfittedwithamechanicalstirrerareplaced200g.oftechnicalflakesodiumhydroxide,200g.ofbenzophenone,2l.of95percentalcohol,and200g.oftechnicalzincdust.Thestirrerisstartedandthemixtureslowlywarmstoabout70°spontaneously.Aftertwotothreehoursthemixture,whichhasstartedtocool,isfilteredwithsuction,andtheresidueiswashedtwicewith100-cc.portionsofhotalcohol.Thefiltrateispouredintofivevolumesoficewateracidifiedwithabout425cc.ofconcentratedcommercialhydrochloricacid.Thebenzohydrolseparatesasawhitecrystallinemassandisfilteredbysuction.Theyieldofcrudeair-driedproductmeltingat65°is194–196g.(96–97percentofthetheoreticalamount).From200g.ofcrudeproductin200cc.ofhotalcoholthereisobtained,aftercoolinginanice-saltmixture,filtering,anddrying,140–145g.ofproductmeltingat68°.Thebenzohydrolremaininginthemotherliquorsmaybeprecipitatedwithwater.3.3金属氢化物还原3.3.1LAH还原Phenanthrenequinone(6g.,0.03mole)isplacedinafritted-glass(coarseporosity)extractionthimbleofaSoxhletapparatusovera1-l.flaskcontainingasuspensionof3g.oflithiumaluminumhydridein500ml.ofanhydrousdiethylether.Extractionofthequinoneoveraperiodof16hoursaffordsagreensolution.Thereactionisquenchedbythecautiousadditionofwaterandneutralizedwithglacialaceticacid.Theetherlayerisseparated,andtheaqueouslayerisextractedwithtwo200-ml.portionsofether.Thecombinedetherextractsarewashedconsecutivelywithaqueoussodiumhydrogencarbonateandwater,thendriedovermagnesiumsulfate.Evaporationofthesolventunderreducedpressuregivesthecrudeproduct,whichisrecrystallizedfrombenzene,giving3.8–4.1g.(62–68%)ofpurediol

1

asfluffy,whiteneedles,m.p.185–190°4.

手性醇的合成4.1CBS还原法A250-mL,three-necked,round-bottomedflaskisequippedwithaTeflon-coatedthermocoupleprobe,a125-mLpressure-equalizingadditionfunnel,nitrogeninlet,andTeflon-coatedmagneticstirringbar.Theflaskischargedwiththe(S)-oxazaborolidine-boranecomplex(2.91g,10.0mmol),purgedwithnitrogen,andchargedwithdrydichloromethane(10mL).Tothestirredsolutionisaddedborane-methylsulfide(10M,20mL,200mmol).Thesolutioniscooledto−20°Candtheadditionfunnelchargedwithasolutionof1-indanone(26.4g,200mmol)indrydichloromethane(75mL).The1-indanonesolutionisthenaddeddropwiseovera4–6hrperiodwhilemaintainingtheinternaltemperatureofthereactionmixtureat−20±5°C.Aftertheadditioniscomplete,thereactionmixtureisstirredfor2hrat−20°C.Afterthereactioniscomplete,themixtureiscautiouslypouredintoa1-Lflaskcontainingmagnetically-stirred,pre-cooled(−20°C)methanol(300mL).Thecoolingbathisremoved,andthestirredmixtureallowedtowarmtoroomtemperature(20–25°C).Afterevolutionofhydrogenceases,themixtureisconcentratedbydistillation(1atm)toavolumeofca.50mL.Methanol(200mL)isadded,andthedistillationrepeated.Theresiduecontainingtheproductanddiphenylprolinolisdilutedwithmethanol(100mL)andthenloadedontoa2.5×30-cmcolumnpackedwithAmberlyst15(NH+)atca.2.5mL/min,collecting40-mLfractions.Thecolumnisrinsedwithmethanoluntiltheproductiseluted.Thecolumnisthenrinsedwith1Mmethanolicammoniauntilthediphenylprolinoliseluted.Thefractionscontainingtheproduct(2–15)arecombined,andthenconcentratedunderreducedpressure(40°C,100mm)togive26.2gofcrudeproductasawhitecrystallinesol