Ch 11- Alcohols and Ethers
Alcohols
• Alcohols are compounds whose molecules
have a hydroxyl group attached to a saturated
carbon atom
• The saturated carbon may be that of a simple
alkyl group
• Examples
• Or the saturated carbon may be connected to
an alkenyl, alkynyl, or benzene ring
Alcohols and Ethers
• Compounds that have a hydroxyl group
attached directly to a benzene ring are called
phenols
• Ethers differ from alcohols in that the oxygen
atom is bonded to 2 carbons
Nomenclature of Alcohol
• See section 4.3f
• Remember that the hydroxyl group has
priority over halogens, double bonds, triple
bonds, and alkyl groups in numbering and
naming.
Nomenclature of Ethers
• Common Name:
• List the two alkyl groups in alphabetical order,
followed with ether
– example
• IUPAC Name:
• IUPAC names are used for more complex ethers or
compounds with more than one ether linkage
• In IUPAC, ethers are named as Alkoxy substitutes
Physical Properties
• Ethers have BP that are roughly comparable
with alkanes of similar molecular weight
• Alcohols on the other hand have much higher
BP’s due to hydrogen bonding
• Ethers can hydrogen bond with water, just not
other ether molecules
• Because of this, both have increased water
solubility.
Synthesis of Alcohols from Alkenes
• We have already covered 3 ways:
1) Acid-Catalyzed Hydration Alkenes:
-Markovnikov addition
-rearrangement possible due to carbocation
2) Oxymercuration-Demercuration
-Markovnikov addition
-no carbocation, no rearrangement
3) Hydroboration-Oxidation
-Anti-Markovnikov product
-no carbocation, no rearrangement
- Stereoselective: gives syn-addition product
Reactions of Alcohols
1) Alcohols as Acids
- The hydrogen of the hydroxyl group can
be abstracted in the presence of bases stronger
than the Alkoxide product
-ex.
-The equilibrium when mixed with
hydroxide favors the alcohol!
Reactions of Alcohols
2) Conversion of Alcohols into Alkyl Halides
A) Via substitution with HX
example:
-primary and methyl via Sn2
-secondary and tertiary via Sn1
-Because Chlorine is a weaker nucleophile,
must add ZnCl2 must be added for primary and
secondary alcohols.
Reactions of Alcohols
• B) Alkyl Bromides using phosphorus tribromide
– Example and Mechanism
– Usually occurs without presence of carbocation
– Preferred method of synthesis of Alkyl Bromide from
alcohol
Reactions of Alcohols
• C) Alkyl Chlorides using Thionyl Chloride
– Example and Mechanism
– Usually done with a tertiary Amine present to
consume HCl
Reactions of Alcohols
3) Tosylates, Mesylates, and Triflates
Leaving Groups/Protecting Groups of Alcohols
The Hydroxyl group of an alcohol can be converted
to a super group or protected by converting it to a
sulfonate ester derivative
Why protect?
• Prevents unwanted reactions
• Differentiates and selectively react certain
alcohols in organic synthesis
Most Common Sulfonate Esters
• The mesyl group, methane sulfonate esters,
(mesylates)
• The tosyl group, p-toluene sulfonate esters,
(tosylates)
• The trifyl group, trifluoromethane sulfonate
esters, (triflates)
Synthesis of Sulfonate Esters
• The desired sulfonate ester is prepared by
reacting the appropriate alcohol with the
desired sulfonyl chloride
• Examples:
Reactions of Sulfonate Esters
• Mesylates, tosylates, and triflates are
frequently used to promote nucleophilic
substitution reactions because they are great
leaving groups.
• example
Reactions of Sulfonate Esters
• They are great leaving groups because the
sulfonate anions are very weak bases and
nucleophiles
• The triflate anion is one of the best of all
known leaving groups.
• Triflates can actually leave to form vinylic
carbocations, which are the least stable of all
carbocations
Reactions of Sulfonate Esters
• Stereochemistry is not affected in the
formation of the sulfonate ester because the
C-O bond is unchanged.
• Example
• For the substitution steps, typical protocol is
followed: Sn2=inverted
Sn1= loss
Mechanism for Sulfonate Ester
• Very straight forward
Synthesis of Ethers
• 1) Intermolecular Dehydration of Alcohols
– Already seen dehydration of alcohol to form
alkenes
– Primary alcohols can dehydrate to form ethers
– Usually occurs at lower temperatures than
required to form alkene
– Promoted by distilling off the ether as it forms
– The process is acid catalyzed:
Synthesis of Ethers
• This method only works with primary alcohols
• Secondary and tertiary alcohols dehydrate to
the alkene before ethers can form.
Synthesis of Ethers
• 2) The Williamson Ether Synthesis
– An important reaction to synthesized
unsymmetrical ethers
– It is an Sn2 reaction with a sodium alkoxide as the
nucleophile and an alkyl halide, sulfonate, or
sulfate as the leaving group
– Example
Note: Since this is an Sn2 reaction, the LG must be
either a methyl, primary or secondary LG!
Synthesis of Ethers
• Typically, Sodium Hydride is used to prepare
the sodium alkoxide
• Example:
• The usual limitations of Sn2 apply:
– Best results with methyl/primary LG
– Tertiary LG only yields elimination
– Substitution favored at low temperature
Synthesis of Ethers
• When synthesizing an ether using this
method, look at the two ether bonds to
decide which is better to make via Sn2
• Example 1- Synthesize 2-methoxypentane
using Williamson Ether synthesis.
Synthesis of Ethers
• Example 2- Synthesize 1-ethoxy-4methylbenzene
Synthesis of Ethers
• YOUR TURN!!
• Example 3- synthesize t-butyl ethyl ether
Synthesis of Ethers
• 3) Synthesis of Ethers by Alkoxymercurationdemercuration
– It is the reaction of an alkene with an alcohol in
the presence of a mercury salt, such as mercuric
acetate, Hg(OAc)2 , mercuric trifluoroacetate, Hg
(OCOCF3)2
– When the alcohol is the solvent, it is called a
Solvomercuration-Demercuration.
Synthesis of Ethers
• This method parallels hydration by
oxymercuration-demercuration we covered
last semester, but instead of water attacking
the merconium bridge, the alcohol does.
• Reaction and Mechanism:
• examples
Problem
• Say you wanted to make 2-t-butoxy-2methylbutane. Which would be the best way,
williamson or mercuration? Evaluate all the
possible ways and give an explanation on why
you chose the one you think is best.
Synthesis of Ethers
• 4) t-butyl ethers by alkylation of alcohols
– Also used as protecting groups
– T-butyl ethers can be made from primary alcohols
by mixing them first with strong acid (H2SO4) then
with 2-methylpropane
– Ex.
– The tbutyl ether, can be hydrolyzed easily with
dilute acid to reform the primary alcohol and
tbutyl alcohol
Use of a Protecting Group
• Example:
Synthesis of Ethers
• 5) Silyl Ether Protecting Group
– Alcohol can also be protected as silyl ethers
– One of the most common is t-butyl dimethyl silyl ether
group (TBDMS)
– TBDMS groups are stable in a pH range of ~4-12
– They are synthesized by mixing the alcohol with tbutyl
chloro dimethyl silane in the presence of an aromatic
amine such as:
– Usually done in aprotic solvent.
Synthesis of Ethers
• Examples:
• The TBDMS group can be removed using the
fluoride ion.
– Tetrabutyl ammonium fluoride (TBAF) or aqueous
HF usually provides the fluoride ion.
• Example:
Reactions of Ethers
• Dialkyl ethers react with very few reagents other
than acids
• This lack of reactivity coupled with the ability to
solvate cations makes ethers especially useful as
solvents
• The Oxygen of the ether linkage makes the ether
basic
• They can accept protons from strong acids to form
oxonium salts
• Example:
Reactions of Ethers
• Heating dialkyl ethers with very strong acids
(HI, HBr, H2SO4) causes a reaction in which the
carbon-oxygen bond breaks.
• Reaction:
• Mechanism:
Epoxides
• Epoxides- are cyclic ethers with a 3 membered
ring
• In IUPAC nomenclature, epoxides are named
as Oxiranes.
• Examples:
Synthesis of Epoxides
• Epoxides are made from reacting alkenes with
an organic peroxy acid (peracid)
• This process is called epoxidation
• Example:
• Possible Mechanism:
Synthesis of Epoxides
• Some peracids are unstable, therefore
dangerous to use.
• Because of its stability, the peracid
magnesium monoperoxy phthalate (MMPP)
• Examples:
Stereochemistry
• Note the stereochemistry!
• Because it’s a 3 member ring, formation of the
epoxide must be syn-addition
• With straight chain alkenes, the reaction is
stereospecific as well
• The resulting oxirane will have the same
configuration as the alkene had!
• Examples:
Reactions of Epoxides
• The highly strained 3 membered ring of
epoxides make them much more reactive
towards nucleophilic substitution
• The opening of the epoxide can either be acid
catalyzed or base catalyzed with different
regiochemistry results.
Acid Catalyzed Mechanism
• Seen with weak nucleophiles:
Base Catalyzed Mechanism
• Seen with strong nucleophiles:
Regioselectivity
• The opening of unsymmetrical epoxides is
regioselective
• In the base catalyzed mechanism, attack by
the strong nucleophile is on the less
substituted carbon
• Ex
• This is expected because it is an Sn2-like
attack!
Regioselectivity
• In the acid catalyzed opening, with the weak
nucleophiles, the nucleophiles attack the More
substituted carbon
• Ex.
• Rationale: In the protonated epoxide, the additional
positive charge on the oxygen adds to the ring
strain already present.
• As a result, bonds start to break leaving a partial
positive charge on the more substituted carbon,
which is where the nucleophile attacks
Regioselectivity
• This is the same reasoning used when the
water attacked the Bromonium or merconium
bridges!!
Problems
Anti 1,2-dihydroxylation of Alkene via
epoxides
• Anti 1,2-diols can be synthesized from alkenes by
first forming the epoxide, then doing an acid
catalyzed opening.
• Example:
• NOTE: This is opposite of the Osmium reaction
we saw in chapter 8 that produced the syn diols