Sulfur-Containing Compounds Organic Chemistry 4th Edition Paula Yurkanis Bruice Chapter 12 Reactions of Alcohols, Ethers, Epoxides, and Sulfur-Containing Compounds Organometallic Compounds Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall

Alcohols and ethers have to be activated before they can undergo a substitution or an elimination reaction Convert the strongly basic leaving group (OH–) into a good leaving group Only weakly basic nucleophiles can be used

Secondary and tertiary alcohols undergo SN1 reactions with hydrogen halides

Primary alcohols undergo SN2 reactions with hydrogen halides

ZnCl can be used to catalyze certain SN2 reactions

Look out for rearrangement product in the SN1 reaction of the secondary or tertiary alcohol

Amines do not undergo substitution reactions because NH2– is a very strong base (a very poor leaving group) RCH2F > RCH2OH > RCH2NH2 HF H2O NH3 pKa = 3.2 pKa = 15.7 pKa = 36 Protonation of the amine moiety does not solve the problem

Other Methods for Converting Alcohols into Alkyl Halides

Activation by SOCl2

Converting Alcohols into Sulfonates

Several sulfonyl chlorides are available to activate OH groups

SN2 of the Activated Sulfonates

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

Look out for carbocation rearrangement

Ring Expansion

Primary Alcohols Undergo Dehydration by an E2 Pathway

The Stereochemical Outcome of the E1 Dehydration

A Milder Way to Dehydrate an Alcohol

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 or organic molecules to form a host–guest complex, an example of molecular recognition

Thiols are sulfur analogs of alcohols ethanethiol 1-propanethiol 3-methyl-1-butanethiol 2-mercaptoethanol are stronger acids (pKa = 10) than alcohols are not good at hydrogen-binding

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 electron cloud is polarized

Organometallic Compounds An organic compound containing a carbon–metal bond

Preparation of Organolithium Compounds hexane 1-bromobutane butyllithium hexane 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, NH2, NHR, SH, C=CH, CO2H)

A Grignard reagent will undergo transmetallation if it is added to a metal halide whose metal is more electropositive than magnesium

Coupling Reactions Formation of carbon–carbon bonds

The Heck Reaction Pd(PPh3)4 (CH3CH2)3N Pd(PPh3)4 (CH3CH2)3N

The Stille Reaction Pd(Ph3)4 THF Pd(Ph3)4 THF

The Suzuki Coupling Pd(PPh3)4 NaOH Pd(PPh3)4 NaOH