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Chapter 11
Alcohols and Ethers
Chapter 11 2
Nomenclature
Nomenclature of Alcohols (Sec. 4.3F)
Nomenclature of Ethers
Common Names The groups attached to the oxygen are listed in alphabetical order
IUPAC Ethers are named as having an alkoxyl substituent on the main chain
Chapter 11 3
Cyclic ethers can be named using the prefix oxa-
Three-membered ring ethers can be called oxiranes;
Four-membered ring ethers can be called oxetanes
Chapter 11 4
Physical Properties of Alcohols and Ethers Ether boiling points are roughly comparable to hydrocarbons of
the same molecular weight Molecules of ethers cannot hydrogen bond to each other
Alcohols have considerably higher boiling points Molecules of alcohols hydrogen bond to each other
Both alcohols and ethers can hydrogen bond to water and have
similar solubilities in water Diethyl ether and 1-butanol have solubilites of about 8 g per 100 mL in water
Chapter 11 5
Synthesis of Alcohols from Alkenes
Acid-Catalyzed Hydration of Alkenes
This is a reversible reaction with Markovnikov regioselectivity
Oxymercuration-demercuration
This is a Markovnikov addition which occurs without
rearrangement
Chapter 11 6
Hydroboration-Oxidation
This addition reaction occurs with anti-Markovnikov
regiochemistry and syn stereochemistry
Chapter 11 7
Alcohols as Acids Alcohols have acidities similar to water
Sterically hindered alcohols such as tert-butyl alcohol are less
acidic (have higher pKa values) Why?: The conjugate base is not well solvated and so is not as stable
Alcohols are stronger acids than terminal alkynes and primary or
secondary amines
An alkoxide can be prepared by the reaction of an alcohol with
sodium or potassium metal
Chapter 11 8
Conversion of Alcohols into Alkyl Halides Hydroxyl groups are poor leaving groups, and as such, are often
converted to alkyl halides when a good leaving group is needed
Three general methods exist for conversion of alcohols to alkyl
halides, depending on the classification of the alcohol and the
halogen desired Reaction can occur with phosphorus tribromide, thionyl chloride or hydrogen
halides
Chapter 11 9
Alkyl Halides from the Reaction of Alcohols with
Hydrogen Halides The order of reactivity is as follows
Hydrogen halide HI > HBr > HCl > HF
Type of alcohol 3o > 2o > 1o < methyl
Mechanism of the Reaction of Alcohols with HX
SN1 mechanism for 3o, 2o, allylic and benzylic alcohols These reactions are prone to carbocation rearrangements
In step 1 the hydroxyl is converted to a good leaving group
In step 2 the leaving group departs as a water molecule, leaving behind a
carbocation
Chapter 11 10
In step 3 the halide, a good nucleophile, reacts with the carbocation
Primary and methyl alcohols undergo substitution by an SN2
mechanism
Primary and secondary chlorides can only be made with the
assistance of a Lewis acid such as zinc chloride
Chapter 11 11
Alkyl Halides from the Reaction of Alcohols with
PBr3 and SOCl2 These reagents only react with 1o and 2o alcohols in SN2 reactions
In each case the reagent converts the hydroxyl to an excellent leaving group
No rearrangements are seen
Reaction of phosphorous tribromide to give alkyl bromides
Chapter 11 12
Reaction of thionyl chloride to give alkyl chlorides Often an amine is added to react with HCl formed in the reaction
Chapter 11 13
Tosylates, Mesylates, and Triflates: Leaving
Group Derivatives of Alcohols The hydroxyl group of an alcohol can be converted to a good
leaving group by conversion to a sulfonate ester
Sulfonyl chlorides are used to convert alcohols to sulfonate esters Base is added to react with the HCl generated
Chapter 11 14
A sulfonate ion (a weak base) is an excellent leaving group
If the alcohol hydroxyl group is at a stereogenic center then the
overall reaction with the nucleophile proceeds with inversion of
configuration The reaction to form a sulfonate ester proceeds with retention of configuration
Triflate anion is such a good leaving group that even vinyl triflates
can undergo SN1 reaction
Chapter 11 15
Synthesis of Ethers
Ethers by Intermolecular Dehydration of Alcohol
Primary alcohols can dehydrate to ethers This reaction occurs at lower temperature than the competing dehydration to an
alkene
This method generally does not work with secondary or tertiary alcohols because
elimination competes strongly
The mechanism is an SN2 reaction
Chapter 11 16
Williamson Ether Synthesis
This is a good route for synthesis of unsymmetrical ethers
The alkyl halide (or alkyl sulfonate) should be primary to avoid E2
reaction Substitution is favored over elimination at lower temperatures
Chapter 11 17
Synthesis of Ethers by Alkoxymercuration-
Demercuration
An alcohol is the nucleophile (instead of the water nucleophile
used in the analogous reaction to form alcohols from alkenes)
tert-Butyl Ethers by Alkylation of Alcohols: Protecting
Groups
This method is used to protect primary alcohols The protecting group is removed using dilute acid
Chapter 11 18
Silyl Ether Protecting Groups
Silyl ethers are widely used protecting groups for alcohols The tert-butyl dimethysilyl (TBDMS) ether is common
The protecting group is introduced by reaction of the alcohol with the
chlorosilane in the presence of an aromatic amine base such as imidazole or
pyridine
The silyl ether protecting group is removed by treatment with fluoride ion (e.g.
from tetrabutyl ammonium fluoride)
Chapter 11 19
Reactions of Ethers Acyclic ethers are generally unreactive, except for cleavage by
very strong acids to form the corresponding alkyl halides Dialkyl ethers undergo SN2 reaction to form 2 equivalents of the alkyl bromide
Chapter 11 20
Epoxides Epoxides are three-membered ring cyclic ethers
These groups are also called oxiranes
Epoxides are usually formed by reaction of alkenes with peroxy
acids This process is called epoxidation and involves syn addition of oxygen
Chapter 11 21
Magnesium monoperoxyphthalate (MMPP) is a common and safe
peroxy acid for epoxidation
Epoxidation is stereospecfic Epoxidation of cis-2-butene gives the meso cis oxirane
Epoxidation of trans-2-butene gives the racemic trans oxirane
Chapter 11 22
Reaction of Epoxides Epoxides are considerably more reactive than regular ethers
The three-membered ring is highly strained and therefore very reactive
Acid-catalyzed opening of an epoxide occurs by initial protonation
of the epoxide oxygen, making the epoxide even more reactive Acid-catalyzed hydrolysis of an epoxide leads to a 1,2-diol
Chapter 11 23
In unsymmetrical epoxides, the nucleophile attacks primarily at
the most substituted carbon of the epoxide
Chapter 11 24
Base-catalyzed reaction with strong nucleophiles (e.g. an alkoxide
or hydroxide) occurs by an SN2 mechanism The nucleophile attacks at the least sterically hindered carbon of the epoxide
Chapter 11 25
Anti 1,2-Dihydroxylation of Alkenes via Epoxides Opening of the following epoxide with water under acid catalyzed
conditions gives the trans diol
Chapter 11 26
Epoxide ring-opening is a stereospecific process
Chapter 11 27