16.9 Preparation 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 vicinal halohydrins, followed by treatment with base (Section 16.10),Preparation of Epoxides,16.10 Conversion of Vicinal Halohydrins to Epoxides,NaOH,H2O,(81%),H,H,O,Example,O,Br,H,H, , , , ,NaOH,H2O,(81%),H,H,O,Example,via:,anti addition,Epoxidation via Vicinal Halohydrins,Br2,H2O,OH,Br,anti addition,inversion,Epoxidation via Vicinal Halohydrins,Br2,H2O,OH,NaOH,corresponds to overall syn addition of oxygen to the double bond,Br,O,anti addition,inversion,Epoxidation via Vicinal Halohydrins,Br2,H2O,OH,NaOH,corresponds to overall syn addition of oxygen to the double bond,Br,H,H3C,CH3,O,H,H,CH3,H3C,H,anti addition,inversion,Epoxidation via Vicinal Halohydrins,Br2,H2O,OH,NaOH,corresponds to overall syn addition of oxygen to the double bond,Br,H,H3C,CH3,O,H,H,H3C,CH3,H,H,CH3,H3C,H,16.11 Reactions 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 method for the synthesis of alcohols).,Reactions of Epoxides,Reaction of Grignard Reagents with Epoxides,CH2,CH2,OMgX,H3O+,R,RCH2CH2OH,H2C,CH2,O,+,1. diethyl ether 2. H3O+,(71%),Example,CH2MgCl,CH2CH2CH2OH,Reactions of epoxides involve attack by a nucleophile and proceed with ring-opening. For ethylene oxide:,NuH,+,NuCH2CH2OH,In general.,For epoxides where the two carbons of the ring are differently substituted:,In general.,Nucleophiles attack here when the reaction is catalyzed by acids:,Anionic nucleophiles attack here:,16.12 Nucleophilic Ring-Opening Reactions of Epoxides,NaOCH2CH3,CH3CH2OH,(50%),Example, ,Mechanism, ,Mechanism, ,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,H2N,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-crowded carbon,Anionic nucleophile attacks less-crowded carbon,1. diethyl ether 2. H3O+,MgBr,+,(60%),(90%),Hydride attacks less-crowded carbon,Lithium aluminum hydride reduces epoxides,1. LiAlH4, diethyl ether 2. H2O,16.13 Acid-Catalyzed Ring-Opening Reactions of Epoxides,Example,CH3CH2OCH2CH2OH,(87-92%),CH3CH2OCH2CH2OCH2CH3 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,Figure 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,Characteristics:,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,