Alcohol & Ether-Chemistry [Gujarat Board-XII-Sem-3-Ch-7]

1. Chapter 11
Alcohols and Ethers

2. 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

3. 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

4. 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

5. 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

6. Chapter 11 6
 Hydroboration-Oxidation
This addition reaction occurs with anti-Markovnikov
regiochemistry and syn stereochemistry

7. 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

8. 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

9. 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

10. 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

11. 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

12. Chapter 11 12
Reaction of thionyl chloride to give alkyl chlorides
Often an amine is added to react with HCl formed in the reaction

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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)

19. 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

20. 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

21. 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

22. 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

23. Chapter 11 23
In unsymmetrical epoxides, the nucleophile attacks primarily
at the most substituted carbon of the epoxide

24. 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

25. 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

26. Chapter 11 26
Epoxide ring-opening is a stereospecific process

27. Chapter 11 27