Chapter 12

Reactions of Alcohols,Ethers, Epoxides, and

Sulfur-Containing Compounds

Organometallic Compounds

Irene LeeCase Western Reserve University

Cleveland, OH

Reactions of Alcohols

•reaction with hydrogen halides

•acid-catalyzed dehydration (E1 Rxn)

•reaction with thionyl chloride

•reaction with phosphorous tribromide & PCl3

•conversion to sulfonate esters

Secondary and tertiary alcohols undergo SN1 reactions with hydrogen halides

Primary alcohols undergo SN2 reactions with hydrogen halides

ZnCl2 can be used to catalyze certain SN2 reactions

Rearrangement of secondary or tertiary alcohols can occur in the SN1 reaction

Amines do not undergo substitution reactions becauseNH2

– is a very strong base (a very poor leaving group)

RCH2F > RCH2OH > RCH2NH2

HF H2O NH3

pKa = 3.2 pKa = 15.7 pKa = 36

Other Methods for Converting Alcohols into Alkyl Halides

Activation by SOCl2

Converting Alcohols into Sulfonates(Excellent Leaving Groups)

Several sulfonyl chlorides are available to react with -OH group

SN2 Reactions of Activated Sulfonates

Dehydration of Alcohols

To prevent the rehydration of the alkene product, one needs to remove the product as it is formed

Carbocation Rearrangement

Ring Expansion

Primary Alcohols Undergo Dehydration by an E2 Pathway

Stereochemistry of the E1 Dehydration

Milder Dehydration

Substitution Reactions of Ethers

Activation of ether by protonation

Reactions of Epoxides

Epoxides

Nucleophilic attack of hydroxide ion on ethylene oxide and on diethyl ether

Ring Opening

When a nucleophile attacks an unprotonated epoxide,the reaction is a pure SN2 reaction

Epoxides Are Synthetically Useful Reagents

Crown Ethers

A crown ether specifically binds certain metal ions ororganic molecules to form a host–guest complex, an

example of molecular recognition

Thiols are sulfur analogs of alcohols

They are stronger acids (pKa = 10) than alcohols, but do not exhibit hydrogen-binding

ethanethiol 1-propanethiol

3-methyl-1-butanethiol 2-mercaptoethanol

In protic solvent, thiolate ions are better nucleophiles than alkoxide ions

CH3OH

The sulfur analogs of ethers are called sulfides or thioethers

Sulfur is an excellent nucleophile because its electroncloud is polarized

Organometallic CompoundsAn organic compound containing a carbon–metal bond

Preparation of Organolithium Compounds

CH3CH2CH2CH2Br + 2 Li CH3CH2CH 2CH 2Li + L iBr

Cl + 2 Li Li + L iCl

hexane

hexane

1-bromobutane butyllithium

chlorobenzene phenyllithium

Preparation of Organomagnesium Compounds

Alkyl halides, vinyl halides, and aryl halides can all be used to form organolithium and organomagnesiumcompounds

However, these organometallic compounds cannot be prepared from compounds containing acidic groups (OH, NH2, NHR, SH, C=CH, CO2H)

Coupling Reactions

Formation of carbon–carbon bonds