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1、16.9Preparation of Epoxides:A Review and a Preview,Epoxides are prepared by two major methods.Both begin with alkenes.,reaction of alkenes with peroxy acids(Section 6.18) conversion of alkenes to vicinalhalohydrins, followed by treatmentwith base (Section 16.10),Preparation of Epoxides,16.10Conversi
2、on of Vicinal Halohydrinsto Epoxides,NaOH,H2O,(81%),H,H,O,Example,O,Br,H,H,NaOH,H2O,(81%),H,H,O,Example,via:,antiaddition,Epoxidation via Vicinal Halohydrins,Br2,H2O,OH,Br,antiaddition,inversion,Epoxidation via Vicinal Halohydrins,Br2,H2O,OH,NaOH,corresponds to overall syn addition ofoxygen to the d
3、ouble bond,Br,O,antiaddition,inversion,Epoxidation via Vicinal Halohydrins,Br2,H2O,OH,NaOH,corresponds to overall syn addition ofoxygen to the double bond,Br,H,H3C,CH3,O,H,H,CH3,H3C,H,antiaddition,inversion,Epoxidation via Vicinal Halohydrins,Br2,H2O,OH,NaOH,corresponds to overall syn addition ofoxy
4、gen to the double bond,Br,H,H3C,CH3,O,H,H,H3C,CH3,H,H,CH3,H3C,H,16.11Reactions of Epoxides:A Review and a Preview,All reactions involve nucleophilic attack at carbon and lead to opening of the ring. An example is the reaction of ethylene oxide with a Grignard reagent (discussed in Section 15.4 as a
5、method for the synthesis of alcohols).,Reactions of Epoxides,Reaction of Grignard Reagentswith Epoxides,CH2,CH2,OMgX,H3O+,R,RCH2CH2OH,H2C,CH2,O,+,1. diethyl ether 2. H3O+,(71%),Example,Reactions of epoxides involve attack by anucleophile and proceed with ring-opening.For ethylene oxide:,NuH,+,NuCH2C
6、H2OH,In general.,For epoxides where the two carbons of thering are differently substituted:,In general.,Nucleophiles attack herewhen the reaction iscatalyzed by acids:,Anionic nucleophilesattack here:,16.12Nucleophilic Ring-OpeningReactions of Epoxides,NaOCH2CH3,CH3CH2OH,(50%),Example,Mechanism,Mech
7、anism,Mechanism,CH3CH2,O,CH2CH2,O,H,Mechanism,(99%),Example,KSCH2CH2CH2CH3,ethanol-water, 0C,Stereochemistry,Inversion of configuration at carbon being attacked by nucleophile Suggests SN2-like transition state,H,OH,H,OCH2CH3,(67%),NH3,H2O,(70%),R,S,R,R,Stereochemistry,H3C,CH3,H3C,CH3,O,H,H,H,H,OH,H
8、2N,Inversion of configuration at carbon being attacked by nucleophile Suggests SN2-like transition state,NH3,H2O,(70%),d+,d-,R,S,R,R,Stereochemistry,H3C,CH3,H3C,CH3,O,H,H,H,H,OH,H2N,H3N,O,H3C,H,H3C,H,NaOCH3,CH3OH,(53%),consistent with SN2-like transition state,Anionic nucleophile attacks less-crowde
9、d carbon,Anionic nucleophile attacks less-crowded carbon,1. diethyl ether 2. H3O+,+,(60%),(90%),Hydride attacksless-crowdedcarbon,Lithium aluminum hydride reduces epoxides,1. LiAlH4, diethyl ether 2. H2O,16.13Acid-Catalyzed Ring-OpeningReactions of Epoxides,Example,CH3CH2OCH2CH2OH,(87-92%),CH3CH2OCH
10、2CH2OCH2CH3 formed only on heating and/or longer reaction times,CH3CH2OH,H2SO4, 25C,Example,HBr,10C,BrCH2CH2OH,(87-92%),BrCH2CH2Br formed only on heating and/or longer reaction times,Mechanism,Mechanism,Figure 16.6 Acid-Catalyzed Hydrolysis of Ethylene Oxide,O,H2C,CH2,+,H,O,H2C,CH2,+,O,H,H,Step 1,Fi
11、gure 16.6 Acid-Catalyzed Hydrolysis of Ethylene Oxide,Step 2,Figure 16.6 Acid-Catalyzed Hydrolysis of Ethylene Oxide,Step 3,Acid-Catalyzed Ring Opening of Epoxides,nucleophile attacks more substituted carbon of protonated epoxide inversion of configuration at site of nucleophilic attack,Characterist
12、ics:,CH3OH,CH3CH,CCH3,CH3,OH,OCH3,(76%),consistent with carbocation character at transition state,Nucleophile attacks more-substituted carbon,H2SO4,Stereochemistry,Inversion of configuration at carbon being attacked by nucleophile,(73%),HBr,H,OH,Br,H,(57%),R,S,R,R,Stereochemistry,H3C,CH3,H3C,CH3,O,H,H,H,H,OH,CH3O,Inversion of configuration at carbon being attacked by nucleophile,R,S,R,R,Stereochemistry,H3C,CH3,H3C,CH3,O,H,H,H,H,OH,CH3O,d+,d+,CH3O,O,H3C,H,H3C,H,H,d+,H,H2O,HClO4,(80%),anti-Hydroxylation of Alkenes,H,OH,OH,H,
