Reactions of Alcohols,

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Chapter 12 Reactions of Alcohols, Ethers,
Epoxides, and Sulfur-Containing
Compounds Organometallic Compounds
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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
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Secondary and tertiary alcohols undergo SN1
reactions with hydrogen halides
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Primary alcohols undergo SN2 reactions with
hydrogen halides
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ZnCl can be used to catalyze certain SN2
reactions

• SN2 rxn is slower b/c Cl- is poorer nucleophile
  than
• Br- or I-.
• ZnCl2 is used as catalyst, generates Zn2 which
  make
• a strong complex with es of the oxygen.

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Look out for rearrangement product in the SN1
reaction of the secondary or tertiary alcohol
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Amines do not undergo substitution reactions
because NH2 is a very strong base (a very poor
leaving group)
RCH2F gt RCH2OH gt RCH2NH2 HF H2O
NH3
pKa 3.2
pKa 15.7
pKa 36
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Other Methods for Converting Alcohols into Alkyl
Halides Better yield
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Activation by SOCl2
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Converting Alcohols into Sulfonates
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Several sulfonyl chlorides are available to
activate OH groups
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Conversion of Alcohols into Sulfonate Esters
Sulfonic acid strong acid
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SN2 of the Activated Sulfonates
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Dehydration of Alcohols
- H2O acts as a base
- To prevent the rehydration of the alkene
product, one needs to remove the product as
it is formed
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Look out for carbocation rearrangement
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Ring Expansion
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Primary Alcohols Undergo Dehydration by an E2
Pathway
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The Stereochemical Outcome of the E1 Dehydration
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A Milder Way to Dehydrate an Alcohol
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Substitution Reactions of Ethers
Activation of ether by protonation using HI
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Reactions of Epoxides
Epoxides
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Nucleophilic attack of hydroxide ion on ethylene
oxide and on diethyl ether
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Ring Opening
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When a nucleophile attacks an unprotonated
epoxide, the reaction is a pure SN2 reaction
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Under Basic Condition
Rxn is pure SN2
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Under Acidic Condition
CO starts to break before the Nu has chance to
attack
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Epoxides Are Synthetically Useful Reagents
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Arene Oxides
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Crown Ethers
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A crown ether specifically binds certain metal
ions or organic molecules to form a hostguest
complex, an example of molecular recognition
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Thiols are sulfur analogs of alcohols
ethanethiol
1-propanethiol
2-mercaptoethanol
3-methyl-1-butanethiol
are stronger acids (pKa 10) than alcohols are
not good at hydrogen-binding
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In protic solvent, thiolate ions are better
nucleophiles than alkoxide ions
CH3OH
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The sulfur analogs of ethers are called sulfides
or thioethers
Sulfur is an excellent nucleophile because its
electron cloud is polarized
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Organometallic Compounds
An organic compound containing a carbonmetal bond
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Preparation of Organolithium Compounds
hexane
1-bromobutane
butyllithium
hexane
phenyllithium
chlorobenzene
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Preparation of Organomagnesium Compounds
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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, CCH, CO2H)
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A Grignard reagent will undergo transmetallation
if it is added to a metal halide whose metal is
more electropositive than magnesium
I.E Mg 184 kcal /mol I.E Cd 207 kcal /mol
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Coupling Reactions
Formation of carboncarbon bonds
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The Heck Reaction
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The Stille Reaction
Pd(Ph3)4
THF
Pd(Ph3)4
THF
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The Suzuki Coupling
Pd(PPh3)4 NaOH
Pd(PPh3)4 NaOH