Chapt 11 Alcohols and Ethers 醇、醚的命名醇、醚的命名醇的制备醇的制备 羟汞化还原反应羟汞化还原反应 硼氢化氧化反应硼氢化氧化反应醇的化学反应醇的化学反应醚的制备醚的制备醚的化学反应醚的化学反应保护基保护基环氧化合物环氧化合物Chapter 11醇醚Structure and Nomencalture lAlcohols: -OH is attached to a saturated carbon atom. lEnols: -OH is attached to an unsaturated carbon atom.CH3CH2OH Ethanol HCCCH2OH 2-PropynolCH2=CHCH2OH 2-PropenolBenzyl alcohollPhenols: -OH is attached to a benzene ring. lEthers are compounds whose molecules have an oxygen atom bonded to two carbon atom. Phenolp-Methylphenol (p-Cresol)CH2=CHCH2OCH3Allyl methyl ether 烯丙基烯丙基Chapter 11醇醚Nomenclature of EtherslIUPAC substitutive names are used for more complicated ethers and for compounds with more than one ether linkage. lEthers are named as alkoxyalkanes, alkoxyalkenes, and alkoxyarenes. lSimple ethers are frequently given common radicofunctional names. Methyl phenyl ether (Anisole茴茴香醚，苯甲醚香醚，苯甲醚)1,2-Dimethoxyethane CH3OCH2CH2OCH32-Methoxypentane1-Ethoxy-4-methylbenzeneChapter 11醇醚lCyclic ethers can be names in several ways.Replacement nomenclature: relating the cyclic ether to the corresponding hydrocarbon ring system and use the prefix oxa- to indicate that an oxygen atom replaces a CH2 group. Oxirane: a cyclic three-membered ether (epoxide). Oxetane: a cyclic four-membered ether.Common names: given in parentheses. Oxacyclopropaneor oxirane(ethylene oxide)1,4-Dioxacyclohexane(1,4-dioxane)Oxacyclobutaneor oxetaneOxacyclopentane(tertahydrofuran)Chapter 11醇醚Physical Properties of Alcohols lAlcohols have much higher b.p. than comparable ethers or hydrocarbons. -H-bondlMethanol, ethanol, both propanols, and tert-butyl alcohol are completely miscible with water. l95%ethanol and 5%water azeotrope(共沸物共沸物,78.15C)lThe solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens. Chapter 11醇醚Physical Properties Ethers lEthers have similar boiling points that are comparable with those of hydrocarbons of the same molecular weight. -The b.p. of diethyl ether (MW = 74) is 34.60C; that of pentane (MW = 74) is 36 0C. lEthers are able to form hydrogen bonds with compounds such as water. lEthers have solubilities in water that are similar to those of alcohols of the same molecular weight. -Diethyl ether and 1-butanol have the same solubility in water, approximately 8g/100 mL at room temperature. Pentane, by contrast, is virtually insoluble in water. Chapter 11醇醚Synthesis of Alcohols from Alkenes lAcid-Catalyzed Hydration of Alkenes: Markovnikovs rule; limited usefulness(rearrangements ) lOxymercuration-Demercuration:Markovnikov addition of H and OH lHydroboration-Oxidation: anti-Markovnikov but syn addition of H and OH Chapter 11醇醚Alcohols from Alkenes through Oxymercuration-Demercuration Complete within 20 s to 10 min at rt or below Step 1: Oxymercuration（羟汞化羟汞化 ） Step 2: Demercuration（脱汞脱汞 ） less than an hourHigh yields, usually greater than 90% Chapter 11醇醚lOxymercuration-demercuration is highly regioselective. lRearrangements of the carbon skeleton seldom occur in oxymercuration- demercuration. Solvomercuration-demercuration:Chapter 11醇醚Hydroboration（硼氢化反应）硼氢化反应）: lCarried out by using the boron hydride (B2H6) called diborane. Great care must be used in handling diborane and alkylboranes because they ignite（自燃）（自燃） spontaneously in air (with a green flame). The solution of THF:BH3 is considerably less prone to spontaneous ignition but still must be used in an inert atmosphere and with care. Chapter 11醇醚lThe Stereochemistry of Hydroboration-a syn addition Hydroboration is regioselective and is anti-Markovnikov steric factors Chapter 11醇醚lThe net result of hydroboration-oxidation is an anti-Markovnikov addition of water to a double bond. lAcid-catalyzed hydration (or oxymercuration-demercuration) of 1-hexene: lHydroboration-oxidation of 1-hexene: Chapter 11醇醚The Stereochemistry of Hydroboration lThe overall result is the syn addition of H and OH. lProtonolysis of Organoboranes Chapter 11醇醚Reactions of Alcohols lThe oxygen atom of an alcohol polarizes both the CO bond and the OH bond: lThe electron pairs on the oxygen atom make it both basic and nucleophilic. lProtonation of the alcohol converts a poor leaving group (OH) into a good one (H2O). It also makes the carbon atom even more positive Substitution reactions become possible. Chapter 11醇醚lAlcohols can react with protonated alcohols to afford ethers. as nucleophilesAt a high enough temperature, and in the absence of a good nucleophile, protonated alcohols are capable of undergoing E1 or E2 reactions. Chapter 11醇醚Alcohols as Acids lAlcohols have acidities similar to that of water. * Methanol is a slightly stronger acid than water l Solvation stabilizes the alkoxide ion and increases the acidity of the alcohol. lIf the R group of the alcohol is bulky, solvation of the alkoxide ion is hindered the alkoxide ion is not so effectively stabilized the alcohol is a weaker acid. Relative Acidity H2O ROH RCCH H2 NH3 RH Chapter 11醇醚Conversion of Alcohols into Mesylates and Tosylatess lAlcohols react with sulfonyl chlorides to form sulfonates. no change of configuration Chapter 11醇醚Mesylates and Tosylates in SN2 Reactions : lAlkyl sulfonates are frequently used as substrates for nucleophilic substitution reactions. The trifluoromethanesulfonate ion (CF3SO2O) is one of the best of all known leaving groups. SN1 reactions and yield vinylic cations. Chapter 11醇醚lAlkyl sulfonates provide an indirect method for carrying out nucleophilic substitution reactions on alcohols Step 2 Step 1 Allkyl sulfonates undergo all the nucleophilic substitution reactions that alkyl halides do. Chapter 11醇醚Conversion of Alcoholsinto Alkyl Halides Hydrogen halides (HCl, HBr, or HI): Phosphorous tribromide (PBr3): Thionyl chloride (SOCl2): Chapter 11醇醚lAlkyl Halides From the Reaction of Alcohols with Hydrogen HalidesThe order of reactivity of the HX is: HI HBr HCl (HF is generally unreactive). The order of reactivity of alcohols is: 3 2 1 methyl. The reaction is acid catalyzed. Chapter 11醇醚lMechanisms of the Reactions of Alcohols with HX l2, 3, allylic, and benzylic alcohols appear to react by an SN1 mechanism. Step 1Step 2MajorrearrangementChapter 11醇醚lAlthough halide ions (particularly I and Br) are strong nucleophiles, they are not strong enough to carry out substitution reactions with alcohols directly. Acid-catalyzed conversion of 1 alcohols and methanol to alkyl halides proceeds through an SN2 mechanism. Chapter 11醇醚lChloride ion is a weaker nucleophile than bromide and iodide ions chloride does not react with 1 or 2 alcohols unless ZnCl2 or some Lewis acid is added. Lucas试剂试剂:浓浓HCl与无水与无水ZnCl2配制的溶液配制的溶液, 试剂用于鉴别不同的试剂用于鉴别不同的醇。醇。Chapter 11醇醚lAlkyl Halides From the Reaction of Alcohols with PBr3 or SOCl2 1 and 2 alcohols react with phosphorous tribromide to yield alkyl bromides. Mechanism Chapter 11醇醚Synthesis of Ethers lDehydration of Alcohols lA Mechanism for the Reaction Chapter 11醇醚The Williamson Synthesis of EtherslThis method is not useful for the preparation of unsymmetrical ethers from 10 alcohols because the reaction leads to a mixture of products: L =OSO2R, or OSO2OR“good leaving group Chapter 11醇醚Best results are obtained when the alkyl halide, sulfonate, or sulfate is 1 (or methyl). If the substrate is 3, elimination is the exclusive result.Substitution is favored over elimination at lower temperatures. Chapter 11醇醚Protecting Groups: tert-Butyl Ethers by Alkylation of alcohols. lThe tert-butyl protecting group can be removed easily by treating the ether with dilute aqueous acid. lPreparation of 4-pentyn-1-ol from 3-bromo-1-propanol and sodium acetylide: Chapter 11醇醚lThe OH group has to be protected first!Silyl Ether Protecting Groups pH 412volatileChapter 11醇醚Reactions of Ethers lEthers resist attack by nucleophiles and by bases.lDialkyl ethers react with very few reagents other than acids. Use as solvents lThe oxygen of the ether linkage makes ethers basic Ethers can react with proton donors to form oxonium salts(氧鎓盐氧鎓盐). lHeating dialkyl ethers with very strong acids (HI, HBr, and H2SO4) cleaves the ether linkage: Chapter 11醇醚lEther Cleavage by Strong Acids The reaction begins with formation of an oxonium ion. An SN2 reaction with a bromide ion acting as the nucleophile produces ethanol and ethyl bromide. Chapter 11醇醚Epoxides lEpoxidation:Syn addition react an alkene with an organic peroxy acid (peracid). Chapter 11醇醚lThe epoxidation of alkenes with peroxy acids is stereospecific: Chapter 11醇醚lThe Chemistry of The Sharpless Asymmetric Epoxidationtitanium(IV) tetraisopropoxide Ti(OiPr)4tert-butyl hydroperoxide t-BuOOHa specific enantiomer of a tartrate ester(酒石酸酒石酸). allylic alcohol to form the epoxide Chapter 11醇醚Reactions of EpoxideslThe highly strained three-membered ring of epoxides makes them much more reactive toward nucleophilic substitution than other ethers. lAcid-Catalyzed Ring Opening of an Epoxide Chapter 11醇醚lIf the epoxide is unsymmetrical, the nucleophile attacks primarily at the more substituted carbon atom in acid-catalyzed ring opening. lBonding in the protonated epoxide is unsymmetrical, which the more highly substituted carbon atom bearing a considerable positive charge; the reaction is SN1 like. 马式加成马式加成Chapter 11醇醚lBase-Catalyzed Ring Opening of an Epoxide lIf the epoxide is unsymmetrical, the nucleophile attacks primarily at the less substituted carbon atom in base-catalyzed ring opening. 反马式加成反马式加成Chapter 11醇醚Anti Hydroxylation of Alkenes via Epoxides lEpoxidation of cyclopentenelAcid-catalyzed hydrolysis of 1,2-epoxycyclopentane Chapter 11醇醚lEpoxidation followed by acid-catalyzed hydrolysis constitutes a method for anti hydroxylation of a double bond. Chapter 11醇醚 Phase-Transfer Catalysis(PTC) lSN2 reactions take place much more rapidly in polar aprotic solvents (DMSO and DMF) .lIn some ways the ideal solvent for an SN2 reaction would be a nonpolar aprotic solvent such as a hydrocarbon or a relatively nonpolar chlorinated hydrocarbon. low boiling points they are inexpensivethey are relatively stablelPhase-transfer catalysts are used with two immiscible phases in contact often an aqueous phase containing an ionic reactant and an organic phase (benzene, CHCl3, etc.) containing the organic substrate. Chapter 11醇醚lThe phase-transfer catalyst (Q+X) is usually a quaternary ammonium halide (R4N+X) such as tetrabutylammonium halide Bu4N+X. lThe phase-transfer catalyst causes the transfer of the nucleophile (e.g. CN) as an ion pair Q+CN into the organic phase. Q+ : lipophilicChapter 11醇醚lAn example of phase-transfer catalysis: lMany other types of reactions using PTC: Oxidation of alkenes Another important PTC: Crown ethers They can transport ionic compounds into an organic phase high efficiency. Chapter 11醇醚Crown Ethers: lCrown ethers are cyclic polymers of ethylene glycol lnamed as x-crown-y lX=the total number of atoms in the ringlY=the number of oxygen atoms. host-guest complexationHost-guest chemistrySupramolecular chmistry: “molecular recognition” Chapter 11醇醚lWhen crown ethers coordinate with a metal cation, they thereby convert the metal ion into a species with a hydrocarbonlike exterior. lCrown ethers render many salts soluble in nonpolar solvents. Chapter 11醇醚lP532l11.25(b)(d)(e)(f)l11.27(c)(d)l11.28(a)(d)l11.33l11.34(a)(d)l11.37l11.46(a)(d)Chapter 11醇醚