columbia大学有机化学课件16_09_13 html

1、16.9Preparation of Epoxides: A Review and a PreviewEpoxides 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 treatmentwith base(Section 16.10)Preparation of Epoxides16.10Conversion

2、of Vicinal Halohydrins to EpoxidesHHOHNaOHH2OOHH(81%)BrExampleHHOHNaOHH2OOHH(81%)Br O via:HH Br ExampleBrBr2H2OOHanti additionEpoxidation via Vicinal HalohydrinsBrBr2H2ONaOHOOHcorresponds to overall syn addition of oxygen to the double bondinversionanti additionEpoxidation via Vicinal HalohydrinsBrH

3、 CBr2H2OHNaOHH3HH3HOCH3OHcorresponds to overall syn addition of oxygen to the double bondinversionanti addition3CCHEpoxidation via Vicinal HalohydrinsBrH CBr2H2OHH3HNaOHH3HHH3HOCH3OHcorresponds to overall syn addition of oxygen to the double bondinversionanti addition3CCH3CCHEpoxidation via Vicinal

4、Halohydrins16.11Reactions of Epoxides: A Review and a PreviewAll 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 Epo

5、xidesRMgXRCH2CH2OMgXCH2OH3O+RCH2CH2OHH2CReaction of Grignard Reagents with EpoxidesCH2H2CCH2MgCl+Odiethyl ether H3O+1.2.CH2CH2CH2OH(71%)ExampleReactions of epoxides involve attack by a nucleophile and proceed with ring-opening.For ethylene oxide:CH2+H2CNuHONuCH2CH2OHIn general.For epoxides where the

6、 two carbons of thering are differently substituted:Nucleophiles attack here when the reaction is catalyzed by acids:RCHAnionic nucleophiles attack here:CH2OIn general.16.12Nucleophilic Ring-Opening Reactions of EpoxidesH2CCH2ONaOCH2CH3CH3CH2OHCH3CH2OCH2CH2OH(50%)ExampleCH3CH2OH2CCH2O MechanismCH3CH

7、2OH2CCH2O CH3CH2OOCH2CH2MechanismCH3CH2OH2CCH2O 2CH3 CH CHCH CHOO3222 OCHHMechanismCH3CH2OH2CCH2O 2CH3 CH CHCH CHOO3222CH3CH2OOCH2CH2 OCH2CH3H OCHHMechanismH2CCH2OKSCH2CH2CH2CH3ethanol-water, 0CCH3CH2CH2CH2SCH2CH2OH(99%)ExampleOCH2CH3HNaOCH CH23HHCH3CH2OHHOOH(67%)Inversion of configuration at carbon

8、 being attacked by nucleophileSuggests SN2-like transition stateStereochemistryCH3H3CRRHRH3CNHHOH3OH NHH2O2SHCH3(70%)Inversion of configuration at carbon being attacked by nucleophileSuggests SN2-like transition stateStereochemistryCH3H3CRRHRH3CNHHOH3OH NHH2O2SHCH3(70%)H3C Hd+d-H3N OHH3CStereochemis

9、tryCH3OCH3H CCHNaOCH33 C3CH CHCCH33CCH OH3OH(53%)HCH3Oconsistent with SN2-like transition stateAnionic nucleophile attacks less-crowded carbonMgBr+H2CCHCH3Odiethyl ether H3O+1.2.CH2CHCH3OH(60%)Anionic nucleophile attacks less-crowded carbonCH(CH2)7CH3H2COHydride attacks less-crowded carbon1.2.LiAlH4

10、, diethyl ether H2OH3CCH(CH2)7CH3OH(90%)Lithium aluminum hydride reduces epoxides16.13Acid-Catalyzed Ring-Opening Reactions of EpoxidesCH3CH2OHH2CCH2CH CH OCH CH OH3222OH2SO4, 25C(87-92%)CH3CH2OCH2CH2OCH2CH3 formed only on heating and/or longer reaction timesExampleHBr10CH2CCH2BrCH CH OH22O(87-92%)B

11、rCH2CH2Br formed only on heating and/or longer reaction timesExampleH2CCH2CH2H2C+O O B BrHrHMechanism BrH2CCH2CH2H2C+O O BH BrHOCH2CH2rHMechanismStep 1H2CCH2H2CCH2+O O HH O HH O+HHFigure 16.6Acid-Catalyzed Hydrolysis of Ethylene OxideHStep 2HOH2CCH2+O H +HO CH2CH2HHOFigure 16.6Acid-Catalyzed Hydroly

12、sis of Ethylene OxideH+Step 3OHHHH O CH2CH2OH HHOHOCH2CH2 +HOFigure 16.6Acid-Catalyzed Hydrolysis of Ethylene OxideCharacteristics:nucleophile attacks more substituted carbon of protonated epoxideinversion of configuration at site of nucleophilic attackAcid-Catalyzed Ring Opening of EpoxidesOCH3H CC

13、HCH OH333CH3CHCCH3CCH SO24CH3OHHCH3O(76%)consistent with carbocation character attransition stateNucleophile attacks more-substituted carbonHHOHHBrOHHBr(73%)Inversion of configuration at carbon being attacked by nucleophileStereochemistryCH3H3CRRHRCH OHH3OHOCH OH3H SOS24HH C3CH3(57%)Inversion of conf