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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 (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 because
NH2– is a very strong base (a very poor leaving group)
RCH2F > RCH2OH > RCH2NH2
HF
pKa = 3.2
H2O
NH3
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 or
organic molecules to form a host–guest complex, an
example of molecular recognition
Thiols are sulfur analogs of alcohols
ethanethiol
3-methyl-1-butanethiol
1-propanethiol
2-mercaptoethanol
They are stronger acids (pKa = 10) than alcohols,
but do not exhibit 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
CH3CH2CH2CH2Br + 2 Li
1-bromobutane
CH3CH2CH2CH2Li + LiBr
butyllithium
hexane
Cl
chlorobenzene
+ 2 Li
Li
phenyllithium
+ LiCl
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)
Coupling Reactions
Formation of carbon–carbon bonds