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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
pKa = 3.2
H2O
pKa = 15.7
NH3
pKa = 36
Protonation of the amine moiety does not solve the
problem
CH3CH2NH3+ + OH-
CH3CH2NH2 + H2O
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
CH3CH2SH
ethanethiol
CH3CH2CH2SH
1-propanethiol
CH3
CH3CHCH2CH2SH
HSCH2CH2OH
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
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)
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
O
CCH3
+
Br
CH3O
O
CCH3
Pd(PPh3)4
CH2
CH2
(CH3CH2)3N
CH3O
+
OTf
Pd(PPh3)4
(CH3CH2)3N
CH CH2
The Stille Reaction
Br
Pd(Ph3)4
+
OTf
+
H2C CHSn(CH2CH2CH2CH3)3
Pd(Ph3)4
Sn(CH2CH2CH2CH3)4
THF
CH
CH2
THF
CH2CH2CH2CH3
The Suzuki Coupling
CH2
Br
H3C
+ CH3CH2CH2
O
B
O
Br
H O
+ CH3CH C B
O
Pd(PPh3)4
CH2
CH2CH2CH3
NaOH
H3C
Pd(PPh3)4
NaOH
CH CHCH3