Chapter 12 Reactions of Alcohols, Ethers, Epoxides, and Sulfur-Containing Compounds Organometallic Compounds Irene Lee Case Western Reserve University Cleveland, OH

Reactions of Alcohols reaction with hydrogen halides acid-catalyzed dehydration (E 1 Rxn) reaction with thionyl chloride reaction with phosphorous tribromide & PCl 3 conversion to sulfonate esters

Secondary and tertiary alcohols undergo S N 1 reactions with hydrogen halides

Primary alcohols undergo S N 2 reactions with hydrogen halides

ZnCl 2 can be used to catalyze certain S N 2 reactions

Rearrangement of secondary or tertiary alcohols can occur in the S N 1 reaction

Amines do not undergo substitution reactions because NH 2 – is a very strong base (a very poor leaving group) RCH 2 F > RCH 2 OH > RCH 2 NH 2 HF H 2 O NH 3 pK a = 3.2 pK a = 15.7pK a = 36

Other Methods for Converting Alcohols into Alkyl Halides

Activation by SOCl 2

Converting Alcohols into Sulfonates (Excellent Leaving Groups)

Several sulfonyl chlorides are available to react with -OH group

S N 2 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 S N 2 reaction

Epoxides Are Synthetically Useful Reagents

Crown Ethers

A crown ether specifically binds certain metal ions or organic molecules to form a host–guest complex, an example of molecular recognition

Thiols are sulfur analogs of alcohols They are stronger acids (pK a = 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 CH 3 OH

The sulfur analogs of ethers are called sulfides or thioethers Sulfur is an excellent nucleophile because its electron cloud is polarized

Organometallic Compounds An organic compound containing a carbon–metal bond

Preparation of Organolithium Compounds 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 organomagnesium compounds However, these organometallic compounds cannot be prepared from compounds containing acidic groups (OH, NH 2, NHR, SH, C=CH, CO 2 H)

Coupling Reactions Formation of carbon–carbon bonds