Download Preparation and Reactions of Epoxides: A Review and more Study notes Organic Chemistry in PDF only on Docsity! 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 H OH Br H NaOH H2O (81%) H H O Example O Br H H •• •• •• •• •••• – via: anti addition inversion Epoxidation via Vicinal Halohydrins Br2 H2O OH corresponds to overall syn addition of oxygen to the double bond Br NaOH O anti addition inversion Epoxidation via Vicinal Halohydrins Br2 H2O OH NaOH corresponds to overall syn addition of oxygen to the double bond O H H H3C CH3 H H CH3 H3C Br HH3C CH3H 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 Stereochemistry Inversion of configuration at carbon being attacked by nucleophile Suggests SN2-like transition state NaOCH2CH3 CH3CH2OHO H H H OH H OCH2CH3 (67%) NH3 H2O (70%) R S R R Stereochemistry H3C CH3 H3C CH3 O H H H H OHH2N 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 OHH2N H3N O H3C H H3C H NaOCH3 CH3OH CH3CH CCH3 CH3 OH CH3O (53%) CC H H3C CH3 CH3O consistent with SN2-like transition state Anionic nucleophile attacks less-crowded carbon Anionic nucleophile attacks less-crowded carbon 1. diethyl ether 2. H3O+ MgBr + O H2C CHCH3 CH2CHCH3 OH (60%) Hydride attacks less-crowded carbon Lithium aluminum hydride reduces epoxides O H2C CH(CH2)7CH3 1. LiAlH4, diethyl ether 2. H2O (90%) OH H3C CH(CH2)7CH3 16.13 Acid-Catalyzed Ring-Opening Reactions of Epoxides Example O H2C CH2 CH3CH2OCH2CH2OH (87-92%) CH3CH2OCH2CH2OCH2CH3 formed only on heating and/or longer reaction times CH3CH2OH H2SO4, 25°C Example O H2C CH2 HBr 10°C BrCH2CH2OH (87-92%) BrCH2CH2Br formed only on heating and/or longer reaction times Mechanism Br •• •••• –•• •• •• O •• Br CH2CH2 H •• •• ••O H2C CH2 + •• HBr •• •• •• ••O H2C CH2 + H Figure 16.6 Acid-Catalyzed Hydrolysis of Ethylene Oxide ••O H2C CH2 + •• O•• H H H+ ••O H2C CH2 + HO•• H H •• Step 1 Figure 16.6 Acid-Catalyzed Hydrolysis of Ethylene Oxide ••O H2C CH2 + H O •• •• H H Step 2 •• + •• O O CH2CH2 H H H •• are common are involved in numerous biological processes Naturally Occurring Epoxides enzyme-catalyzed oxygen transfer from O2 to alkene enzymes are referred to as monooxygenases Biosynthesis of Epoxides + + C C + +O2 H+ C C O NADH H2O + NAD + enzyme this reaction is an important step in the biosynthesis of cholesterol Example: biological epoxidation of squalene O2, NADH monoxygenase O 16.15 Preparation of Sulfides prepared by nucleophilic substitution (SN2) Preparation of RSR' + R' XSR – •• •• •• •• R S R' •• CH3CHCH CH2 Cl NaSCH3 methanol CH3CHCH CH2 SCH3 16.16 Oxidation of Sulfides: Sulfoxides and Sulfones either the sulfoxide or the sulfone can be isolated depending on the oxidizing agent and reaction conditions Oxidation of RSR' •• R S R' •• •• R S R' O•• •••• – + sulfide sulfoxide R S R' O•• •••• – ++ O•••• •• – sulfone Example •• SCH3 •• NaIO4 •• SCH3 O•• •••• – + Sodium metaperiodate oxidizes sulfides to sulfoxides and no further. (91%) water Example H2O2 1 equiv of H2O2 or a peroxy acid gives a sulfoxide, 2 equiv give a sulfone (74-78%) (2 equiv) •• SCH •• CH2 SCH O•• •••• – ++ CH2 O•••• •• – 16.17 Alkylation of Sulfides: Sulfonium Salts product is a sulfonium salt Sulfides can act as nucleophiles + R" XSR •• •• R S R" •• R' R' + X– Example CH3(CH2)10CH2SCH3 CH3I CH3(CH2)10CH2SCH3 CH3 + I–
