Chapter 7 Alcohols

1、Chapter 7Alcohols, Ethers, and Epoxides(醇、醚、环氧化物醇、醚、环氧化物)Text 1: Chapter 10, 11, 14I. Alcohol (醇醇) The origins of alcohols Ethyl alcohol (ethanol): grain alcohol（酒精） Methyl alcohol (methanol): wood alcohol（木醇） Role of alcohols Reagents Solvents Synthetic intermediates (合成中间体)1. Structure of alcohols

2、HOH104.5OHmethanol甲醇Phenol苯酚CHOH3CCHOHH2CEnol (烯醇)Aldehyde (醛)sp3sp2sp2tautomerism互变异构sp3CH3CH2OHCH3OH108.9ethanol乙醇sp32. Classification of alcohols According to the type of carbinol carbon atom alcohols can be classified as follows: CHRHOHCHRROHCRRROHprimary alcohol(伯醇) 1secondary alcohol(仲醇)2terti

3、ary alcohol(叔醇)33. Nomenclature of AlcoholsCH3OHIUPAC names:alkanealkanolCommon names:中文:alkyl alcoholXX醇methanol(methyl alcohol)甲醇CH3CH2OHethanol(ethyl alcohol)乙醇CH3CHCH3OH2-propanolpropan-2-ol(isopropyl alcohol)2-丙醇; 异丙醇CH3CH2CH2CH2OH1-butanolbutan-1-ol(n-butyl alcohol)1-丁醇; (正丁醇)CH3CH2CH OHCH32-b

4、utanolbutan-2-ol(sec-butyl alcohol)2-丁醇; (仲丁醇)CH3CH CH2OHCH32-methyl-1-propanol2-methylpropan-1-oliso-butyl alcohol2-甲基-1-丙醇; (异丁醇)CH3C OHCH3CH32-methyl-2-propanol2-methylpropan-2-olt-butyl alcohol2-甲基-2-丙醇; (叔丁醇)CH2CHCH2CHCH3OH4-penten-2-olpent-4-en-2-ol4-戊烯-2-醇CH3CCHOHCH3CH3COH2-hydroxy-3,3-dimeth

5、ylbutanal2-羟基羟基-3,3-二甲基丁醛The order of precedence of functional groups for assigning IUPAC namesAcidsEstersAldehydesKetonesAlcoholsAminesAlkenesAlkynesAlkanesEthersHalidesDecreasing priorityCH2OHH2CCHCH2OHHCCCH2OHphenylmethanol(benzyl alcohol)苯甲醇苄(基)醇2-propenol(allyl alcohol)2-丙烯醇 烯丙醇2-propynol2-丙炔醇炔

6、丙醇cyclohexanol环已醇OHHHBrOHtrans- 2-bromocyclohexanol(1R,2R)-2-bromocyclohexanolNames of diolsCH3CH CHOHCH3OHbutane-2,3-diol2,3-丁二醇CH2CH2OHOHethane-1,2-diol(ethylene glycol)乙二醇glycol (甘醇)= 1,2-diol = vicinal diol, 邻位二醇OHOHOHBrBrBr2-bromophenol(ortho-bromophenol)2-溴苯酚邻溴苯酚3-bromophenol(meta-bromophenol)

7、3-溴苯酚间溴苯酚4-bromophenol(para-bromophenol)4-溴苯酚对溴苯酚Names of phenolso-, m-, p-邻, 间, 对4. Physical properties of alcoholsp Boiling points: Alcohols have much higher boiling points than ethers or hydrocarbons having similar molecular weight. p Solubility: C1-3, miscible with water. ROHHOR hydrophobic regi

8、on 疏水区hydrophilic region亲水区Problem 10-34Predict which member of each pair has the higher bp, and explain the reasons for your predictions. 1-hexanol or 3,3-dimethyl-1-butanol 2-hexanone or 2-hexanol 2-hexanol or 1,5-hexanediol 2-pentanol of 2-hexanolImportant alcoholsMethanol is highly toxic,it can

9、cause blindness or death. MethanolEthanolYeastCH3CH2OHC6H12O6+ CO2Sugar酵母95%CO + 2 H2300-400oC200-300atmZnO-Cr2O3CH3OHCH3CH2OHCH2=CH2Ethanol+ H2OH+acid5. Synthesis of alcoholsu (A) Hydration of alkenes+H2OH+H OH2) Synthesis of alcohols from alkenes1) Synthesis of alcohol from alkyl halideSN2 reactio

10、nC+ intermediateu(B) oxymercuration-Demercuration(羟汞化脱汞)+H2O( 1 ) Hg(OAc)2 / THFOHHgOCOCH3Oxymercuration( 2 ) NaBH4 / H2OOHHDemercuration (脱Hg)anti addtionfollow Mars ruleu(C) Hydroboration-oxidation (硼氢化-氧化反应)+H BHHHydroborationC CH BOrganoboraneBoron hydrideAlkeneTHFH2O2, NaOHC CH OHsyn additionan

11、ti Mars productProblem: (10-37)Show how you would synthesize the following alcohols from appropriate alkenes.OHCH3OHOHOH3) Synthesis of alcohols from carbonyl compounds (由羰基化合物制醇）carbonyl group 羰基carboxylic ester羧酸酯aldehyde醛ketone酮carboxylic acid羧酸C ORCHORCRORCHOORCROOCONu:-NuCONucleophilic addition

12、(亲核加成亲核加成)NuCOHH2O or H3O+alkoxide ion(A) Reaction of carbonyl compounds with organometallic reagents to give alcoholsCOR2R1RCC+CCR1R2OCRCCR1R2OHCR H3O+alkynol (炔醇)Organometallic compounds （有机金属化合物）（有机金属化合物）Compounds that contain carbon-metal bonds (C-M) are called organometallic compounds. C:-M+M =

13、 Na+ or K+(Primarily ionic)(a) highly reactive Nu;(b) powerful B.C:MM = Mg or Li + -(a) great important in organic synthesis; (b) relatively stable in ether solutions. (Primarily covalent)CMM = Pb, Sn, Hg, or TI(a) much less reactive;(b) often volatile (挥发性的) and are stable in air; (c) all poisonous

14、;(d) generally soluble in nonpolar solvents. Tetraethyllead has been used as an antiknock compound in gasoline.Preparation of organolithium and organomagnesium compoundsOrganolithium compounds (有机锂化合物）(Butyl bromide)CH3CH2CH2CH2Br + 2 Li- 10oCEt2OCH3CH2CH2CH2Li + LiBrButyllithium(80-90%)The order of

15、 reactivity of halides is:RXX+ 2 LiRLi + LiX(or ArLi)ArRI RBr RClGrignard reagents （格利雅试剂, 格氏试剂）RX + MgRMgXEt2Oor THFArX + MgEt2Oor THFArMgXGrignard reagentsCH3I + MgCH3MgIEt2Oor THFC6H5Br + MgEt2Oor THFC6H5MgBrMethylmagnesium iodide(95%)Phenylmagnesium bromide(95%)RMgXOORMgXH3CH2COH3CH2COCH2CH3CH2C

16、H3Grignard reagents are stable in etherPreparation of alcohols by the addition of Grignard reagents to carbonyl compoundsNucleophilic addition+RMgX + - + -H+RCEt2OH2OCOAldehyde or Ketone or esterAlcoholsOHRCOMgXFormaldehydePrimary alcoholGrignard reagentHigher aldehydeSecondary alcoholGrignard reage

17、ntKetoneTertiary alcoholGrignard reagent+C6H5MgBr Et2OHCHOC6H5CH2OMgBrH+C6H5CH2OHH2OAcetaldehyde乙醛+CH3CH2MgBr Et2OH3CCHOCH3CH2CHOMgBrCH3H+CH3CH2CHOHH2OCH3+C6H5MgBr Et2Ocyclohexanone环己酮OOMgBrH+H2OOH+RMgBr Et2ORCROOestersRCORROMgBrBrMgORRCRO KetonesRMgBrRCRROMgBrH+H2ORCRROHGrignard reagentesterketonet

18、ertiary alcoholGrignard reagentOrganolithium reagents (RLi) react with carbonyl compounds in the same way as Grignard reagents.RLi+CO RCOLiH3O+RCOHCH3Li+H3CCH3CO H3CCCH3CH3OLiH3O+H3CCCH3CH3OHRCCH+RMgXR H+RCCMgXRCCH + RLiR H+ RCCLiCH3MgI+ H2OCH4 +MgOHICH3MgI+ HOCH3CH4 +MgOCH3ISide reactions of organo

19、metallic reagents体系中不能有活泼氢体系中不能有活泼氢, 如如 O-H, N-H, S-H, -CC-H;底物中不能含有其它极性多重键底物中不能含有其它极性多重键,如如 C=O, C=N, CN, S=O, N=O.Attention!CH3MgBrHOCH2CH2CCH3OHOCH2CH2COMgBrCH3CH3+CH3MgBr+ HOCH2CH2CCH3OCH4+ BrMgOCH2CH2CCH3OXRCOOH H ReductionRCH2OHCarboxylic acid1o AlcoholsRCOOR H ReductionRCH2OH1o Alcohols+ ROHR

20、COH H ReductionRCH2OHAldehyde1o AlcoholsRCOR H ReductionRCHKetone2o AlcoholsOHR2) Reduction of carbonyl compounds to give alcohols (10-11, 11-1)LiAlH4 lithium aluminum hydride 氢化铝俚，四氢铝锂 NaBH4sodium borohydride 硼氢化钠硼氢化钠aldehydesketonesacidsestersNaBH4LiAlH4COLiAlH4NaBH4H-CO-HHOHCOHHhydride transfernu

21、cleophile addition(A)CH3COOHCH3CH2OHCH3CH3COOH2,2-Dimethylpropanoic acid1. LiAlH4 / Et2O2. H2OAcetic acidEthanolCH31. LiAlH4 / Et2O2. H2OCH3CH3CH2OHCH3Neopentyl alcohol 新戊醇 (92%)CH3CH2CH2CHOButanal1-ButanolReductionNaBH4SodiumBorohydrideH2O+CH3CH2CH2CH2OHCH3CH2CCH3Butanone2-ButanolReductionNaBH4Sodi

22、umBorohydrideH2O+CH3CH2CHCH3OOHLiAlH4 + H2O H2 + LiOH + Al(OH)3NaBH3 + H2O H2 + NaOH + B(OH)3fastslowLiAlH4: dry Et2O, THF as solventsNaBH4: EtOH, MeOH, etc. as solventsOC+H2Raney NiOHCH(B) Catalytic hydrogenation of aldehydes and ketonesCH2CHCH2CCH3CH3COH+ H2Raney NiCH3CH2CH2CCH3CH3CH2OHProblems: g

23、ive the main products. CH3CH2CHCHCHOLiAlH4H2OOOHOi. NaBH4ii. H2O, pH = 7AssignmentsText 1: 10-31, 33, 38, 44, 49 Oxidation (氧化) substitution dehydration (脱水) Esterification （酯化）7. Reactions of alcoholsR O HuReduction (还原还原)of an organic molecule usually corresponds to increasing its hydrogen content

24、 or to decreasing its oxygen content.(加氢、去氧或去卤加氢、去氧或去卤素素, 增加键数或减少键数增加键数或减少键数)uOxidation (氧化氧化): increasing the oxygen content of an organic molecule or decreasing its hydrogen content.(加氧或加卤素、去氢，加氧或加卤素、去氢，减少减少键数或增加键数或增加键数键数)Oxidation-Reduction reactions in organic chemistry1) Oxidation of alcohols (

25、11-1, 2, 3)RCOOH H ReductionRCOHCarboxylic acidAldehydeoxygen content decreasesRCOH H ReductionRCH2OHAldehydeAlcoholhydrogen content increases H ReductionRCH3AlcoholAlkanesoxygen content decreasesRCH2OHC-O, 32C-O, 21C-O, 10 O RCH2ClAlkanesRCH3 H O H RCHCl2 O H RCCl3Problem 11-1 p 446 RCHOH O RC2o al

26、coholketoneRRORCH2OH O RCHORCOOH1o AlcoholAldehydeCarboxylic acid O Tertiary alcoholsPrimary alcoholsaldehydescarboxylic acidsSecondary alcohols ketonesdifficult to be oxidized.(A) Oxidization with Cr(VI) (11-2)Oxidants: K2Cr2O7 or Na2Cr2O7 / H2SO4 CrO3/ H2SO4OHCyclooctanolH2CrO4Acetone 35 COCyclooc

27、tanone环辛醇环辛酮CH3CH2CH2CH2OH1-ButanolK2Cr2O7H2SO4CH3CH2CH2CHOButanalK2Cr2O7H2SO4CH3CH2CH2COOHbutyric acidMechanism of chromate oxidations （铬酸氧化机理）（铬酸氧化机理）Step 1RCROHH+HOCrOOOHRCROHCrOOOH+ H2OChromate ester (铬酸酯）RCROHCrOOOHRCRO+ HCrO3-+ H3O+Step 2KetoneCr 6+Cr4+6+4+H2OChromate ester (铬酸酯）OrA Chemical t

28、est for 1, 2, and 3 alcoholsalcoholphenomenon1greenish opaque solution Cr3+2greenish opaque solution Cr3+3No reactionReagent: CrO3 / aqueous H2SO4 or Na2Cr2O7 / aqueous H2SO4 CH3CH2CH2CH2OH1-ButanolCH3CH2CH2CHOButanalPCC25 oCCH2Cl2CrO3 + HCl +NNHCrO3Cl-+Pyridinium chlorochromate吡啶三氧化铬Pyridine PCC (P

29、yridinium chlorochromate, 吡啶三氧化铬) PDC (Pyridinium dichromate, 重铬酸吡啶盐)Oxidation with KMnO4, or HNO3 (11-3)CH3CH2CHCH3OH2-ButanolKMnO4, KOHCH3CH2CCH3OButanoneCH3CH2CH2CH2OH1-ButanolCH3CH2CH2COOKKMnO4, KOHHClCH3CH2CH2COOHIf the conditions are not controlled, KMnO4 or HNO3 will cleave the carbon-carbon

30、bonds.OHKMnO4COOHCOOHCH3CH2OHCu300 oCCH3CHO + H2DehydrogenationCatalytic dehydrgenation (11-3)Swern oxidation: convert alcohols to aldehyde or ketone DMSO/(COCl)2/Et3N/CH2Cl2COH C-O bondO-H bondare polarizedHydrogen can be replaced by sodium (Na) and potassium (K)The hydroxyl group can be replaced b

31、y other groups.2) Substitution ROH + NaRONa + H2ROH + KROK + H2reactivity of alcohols:CH3OH 1 2 3(CH3)3COH + KH(CH3)3COK + H2OH+ NaOHONa+ NaOH+ H2O(1) Acidity of alcohols and phenols (10-6)pKa = 10(2) Conversion of alcohols into alkyl halidesROHHX+RX+H2O(NaX + H2SO4)A.COH+HXStrong acidAlcoholCOHH+Pr

32、otonated alcohol质子化的醇+ X-1 alcohols, SN23 alcohols, SN1reactivity :HI HBr HCl3 2 1 HICH3CH2CH2CH2OHCH3CH2CH2CH2I + H2OheatingHBr, H2SO4CH3CH2CH2CH2OHCH3CH2CH2CH2Br + H2OheatingHCl, ZnCl2CH3CH2CH2CH2OHCH3CH2CH2CH2Cl + H2Oheating+ H2O(CH3)3COHconcd HCl(CH3)3CClr.t.The Lucas reagent: HCl / ZnCl2H CCH3C

33、H3OHZnCl2H CCH3CH3OZnCl2HCCH3CH3HcarbocationCl H CCH3CH3Cl+HOZnCl2The Lucas test: To distinguish 1, 2, and 3 alcohols alcoholTime to react (min)phenomenon16No reaction or react very slow215Emulsion (乳状)3 HBr HCl.The molecule must not contain any acid-sensitive functional group!CH3CH2OCH2CH3+HBr(HI)2

34、 CH3CH2Br + H2OCH3CH2OCH2CH3+ HBrCH3CH2OH+CH2CH3+ Br-An oxonium saltSN2CH3CH2OH + CH3CH2BrHBrCH3CH2OHH+Br-CH3CH2BrSN2CH3O CCH3CH3CH3HICH3O CCH3CH3CH3HIHCH3OH+CCH3CH3CH3SN1CH3OH+ICCH3CH3CH3I Phenyl ethersOCH2CH3HBrOCH2CH3HBrOH+CH3CH2BrEthyl phenyl etherProtonated ether Phenol + ethyl bromideHBrBrNo f

35、urther reaction伯烷基醚按伯烷基醚按S SN N2 2机制断裂，机制断裂，叔烷基醚按叔烷基醚按S SN N1 1机制断裂，机制断裂，芳基烷基醚总是烷氧键断裂。芳基烷基醚总是烷氧键断裂。Odiphenyl ether二二苯苯醚醚?Propose a mechanism. CH3CH2OCH2CH3O2CH3CH2OCHCH3OOHa hydroperoxideautoxidationCH3CH2OOCH2CH3+diethyl peroxideAdd FeSO4 to remove a hydroperoxide!Peroxides test: KI/starch(淀粉淀粉), o

36、r FeSO4/KSCN, etc.2) Autoxidation of ethers5. Important ethers Diethyl ether: bp 35 C, polar solvent THF: bp 66 C, strong polar solvent Crown ethers: as PTC (相转移催化剂)使用乙醚注意事项使用乙醚注意事项 蒸馏时不能蒸干！蒸馏时不能蒸干！ 蒸馏时尾接管要通下水道！蒸馏时尾接管要通下水道！ 周围不能有明火！周围不能有明火！ 不能在冰箱里敞口存放！不能在冰箱里敞口存放！ 萃取时要及时放气萃取时要及时放气!Structural characte

37、ristic: Containing more than three OCH2CH2O- units in one molecule. OOOOOOOOOOOOOO12-crown-412-冠-415-crown-515-冠-5Crown Ethers （冠醚）（冠醚）Nomenclature: x-crown-y x-total atom number in the ring y-oxygen atom numberOOOOOOOOOOOO18-crown-6Dibenzo-18-crown-6二苯基-18-冠-6Dicyclohexyl-18-crown-6二环己基-18-冠-6OOOOO

38、ONH4+K+OOOOOOPhase-Transfer catalysis (PTC) (相转移催化）相转移催化）RX + NaCNQ+X- ( (季季铵铵盐盐）RCN + NaXSN2 reaction Without catalyst, long time is needed to finish this reaction. Addition of Q+X- can speed up the reaction. Q+X-(CH3(CH2)3)4N+X-(CH3(CH2)3)4N+Cl- ( (四四丁丁基基氯氯化化铵铵）RX + NaCNQ+X- (季铵盐）RCN + NaXSN2 reac

39、tionRXNaCNaqueous phaseOrganic phase(CH2Cl2)(水相 ）add Q+X- (季铵 盐）Q+X-+RCNQ+CN+ RXNaCN+ Q+X-NaX+Q+CNQ+X-(CH3(CH2)3)4N+X-(CH3(CH2)3)4N+Cl- ( (四四丁丁基基氯氯化化铵铵）Crown ethers are also used as phase-transfer catalysts.OOOOOO18-Crown-618-冠-6K+MnO4-18-Crown-618-冠-6K+CN-oxidant氧化剂nucleophile亲核试剂OOOOOOK+MnO4(or CN

40、)C6H5CH2Cl + KFSN2 reaction18-Crown-6C6H5CH2F + KCl100%C6H5CH2Cl + KCNSN2 reaction18-Crown-6C6H5CH2CN + KClCH3(CH2)5CH=CH2 + KMnO4CH3(CH2)5COOH18-Crown-6Summary for ethersuNomenclature: “alkyl alkyl ether”, “alkoxy alkane”(IUPAC)uSynthesis Ethers by intermolecular dehydration of alcohols (醇的分子间脱水制醚）

41、 The Williamson synthesis of ethers (醚的威廉姆逊合成）醚的威廉姆逊合成） Alkoxymercuration-demercurationuReactions Cleavage of ethers by HBr and HI Autoxidation of ethersuApplication Solvents: stable, low bp., diethyl ether, THF, 1,4-dioxane Crown ethers: as PTCEpoxides 环氧化物环氧化物OHHMCPBAcyclohexene oxideOHHHH3Ctrans-

42、1,2-epoxy-4-methylcyclohexanetrans-4-甲基甲基-1,2-环氧环氧环己烷环己烷OH(H3C)2HCCH2CH3CH2CH32,2-diethyl-3-isopropyloxirane2,2-二乙基二乙基-3-异丙基异丙基环氧乙烷环氧乙烷CCOan epoxide环氧化物环氧化物OIUPAC: oxiraneCommon: Ethylene oxide 环氧乙烷环氧乙烷1. Synthesis of epoxides1) Epoxidation of alkenes2) Base-Promoted cyclization of halohydrinsCC+RCO

43、OHOORCOHO+CCXOHCCONaOH+ HX1) Epoxidation of alkenesCC+RCOOHOORCOHO+peroxyacid过氧酸CH3COOHOCOOHOCOOHOClperoxyacetic acid peroxybenzoic acid m-chloroperoxybenzoic acid 过过氧乙酸氧乙酸 过过氧苯甲酸氧苯甲酸间氯过间氯过氧苯甲酸氧苯甲酸 (MCPBA)Stereochemistry: the epoxide retains the stereochemistry present in the alkene.epoxide环氧化物2) Ba

44、se-Promoted cyclization of halohydrinsCCXOHX = Cl, Br, I+-OHCCXO-CCOCCXOHCCONaOH+ HX2. Reactions of epoxides1) Acid-catalyzed ring opening (review)CCOH+CCOH+H2OCCOH+OH2- H+CCOHOH1,2-DiolsNu: H2O ROH HXOrientation of acid-catalyzed epoxides openingSN2H2CCCH3OCH3CH2OHCH3H+HOCH2CCH3OCH2CH3CH3H+HOCH2CH(CH3)2OCH2CH3+ H+酸性条件下酸性条件下, 亲核试剂进攻取代基多的碳亲核试剂进攻取代