Chapter-2-Alcohols-and-Ethers.lecture.presentation

Alcohols and ethers

1. Chapter 2
Alcohols and Ethers

2. ❖Alcohols have a hydroxyl (–OH) group bonded to a
saturated carbon atom (sp
3
hybridized)
Structure of Alcohols and Ethers

4. Phenols
•Compounds that have a hydroxyl group attached directly to a
benzene ring

5. Ethers
•The oxygen atom of an ether is bonded to two carbon atoms

6. ▪Ether boiling points are roughly comparable to
hydrocarbons of the same molecular weight.
▪Alcohols have considerably higher boiling points
since molecules of alcohols hydrogen bond to each
other.
▪Both alcohols and ethers can hydrogen bond to
water and have similar solubilities in water.
Physical Properties of Alcohols and Ethers

9. Some Important Alcohols and Ethers
➢ Ethylene oxide is the starting material for polyethylene
oxide (PEO, also called polyethylene glycol, PEG) used
for covalent attachment to therapeutic proteins such
as interferon, a use that has been found to increase the
circulatory lifetime of the drug.

➢ PEO is also used in some skin creams and as a laxative prior to
digestive tract procedures.

10. ➢ Albuterol is used in some
commonly prescribed
respiratory medications.
➢ Vanillin is used as flavoring.

11. ❖Methanol is highly toxic
❖Ingestion of even small quantities of methanol can cause
blindness
❖Large quantities cause death
❖Methanol poisoning can also occur by inhalation of the
vapors or by prolonged exposure to the skin
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Methanol

12. ❖Ethanol can be produced by
•Fermentation
•Acid-catalyzed hydration of ethene
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Ethanol

13. a good automobile
anti-freeze
as a low-toxicity,
environmentally friendly
alternative
to ethylene glycol
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Ethylene and Propylene Glycols

14. ❖Diethyl ether is a very low boiling, highly flammable liquid
❖Most ethers react slowly with oxygen by a radical process
called autoxidation to form hydroperoxides and peroxides
© 2014 by John Wiley & Sons, Inc. All rights reserved.
Diethyl ether

16. ▪Acid-Catalyzed Hydration of Alkenes
•This is a reversible reaction with Markovnikov
regioselectivity.
alkene
alcohol
Synthesis of Alcohols from Alkenes

17. ▪Oxymercuration-demercuration
•This is a Markovnikov addition which occurs
without rearrangement.
Oxymercuration
Demercuration

18. ▪Hydroboration-Oxidation
•This addition reaction occurs with anti-Markovnikov
regiochemistry and syn stereochemistry.

20. Reactions of Alcohols
▪ mainly due to the following:
• The oxygen atom of the hydroxyl group is nucleophilic
and weakly basic.
• The hydrogen atom of the hydroxyl group is weakly acidic.
• The hydroxyl group can be converted to a leaving group
so as to allow subsitution or elimination reactions.
➢Polarization of the O-H bond
makes the H partially positive
making the alcohol a weak acid.

21. • The electron pairs on the oxygen atom make it both
basic and nucleophilic. In the presence of strong acids,
alcohols act as bases and accepts protons:
➢ The protonation converts a poor leaving group (-OH) into a good
one (H
2O).
➢ Also makes the C more positive and substitution (S
N1 or S
N2)
reactions become possible, the type depending on the class of
alcohols.

22. • Since alcohols are nucleophiles, they too can react
with protonated alcohols: an important step in the
synthesis of ethers.
• At high T and in the absence of a good nucleophile,
protonated alcohols may undergo E
1 or E
2 reactions
(alcohol dehydrations ).
• Alcohols also react with PBr
3 and SOCl
2 to yield alkyl
bromides and alkyl chlorides.

23. ▪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 as Acids

24. ▪Alcohols are stronger acids than terminal
alkynes and primary or secondary amines.
HO
–
and RO
–
order reversed for R = CH
3
H
2O and ROH order reversed for R = CH
3

25. ▪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.
Conversion of Alcohols into Alkyl Halides

27. ▪The order of reactivity is as follows:
•Hydrogen halide HI > HBr > HCl > HF
•Type of alcohol 3
o
> 2
o
> 1
o
< methyl
▪Mechanism of the Reaction of Alcohols with HX
•S
N1 mechanism for 3
o
, 2
o
, allylic and benzylic
alcohols.
➢These reactions are prone to carbocation
rearrangements.
Alkyl Halides from the Reaction of Alcohols
With Hydrogen Halides

28. ➢In step 1 the hydroxyl is converted to a good
leaving group.
Step 1

29. •In step 2 the leaving group departs as a water
molecule, leaving behind a carbocation.
•In step 3 the halide, a good nucleophile, reacts with
the carbocation.

30. ▪Primary and methyl alcohols undergo substitution
by an S
N2 mechanism:

31. ▪Primary and secondary chlorides can only be
made with the assistance of a Lewis acid such
as zinc chloride:

32. ▪These reagents only react with 1
o
and 2
o
alcohols
in S
N2 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:
Alkyl Halides from the Reaction of Alcohols
With PBr
3 and SOCl
2

34. ▪Reaction of thionyl chloride to give alkyl chlorides
•Often an amine is added to react with HCl formed in
the reaction.

36. ▪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.
Synthesis of Ethers

37. •The mechanism is an S
N2 reaction:
This is an acid-base reaction in which the alcohol
accepts a proton from the sulfuric acid.
Another molecule of the alcohol acts as a nucleophile
and attacks the protonated alcohol in an S
N2 reaction.
Step 1
Step 2

38. •The mechanism is an S
N2 reaction:
Another acid-base reaction converts the protonated ether
to an by transferring a proton to molecule of water
(or to another molecule of the alcohol).
Step 3

39. ▪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).

40. ▪Acyclic ethers are generally unreactive, except
for cleavage by very strong acids (HBr, HI) to
form the corresponding alkyl halides.
•e.g. Dialkyl ethers undergo S
N2 reaction to form
2 equivalents of the alkyl bromide.
Reactions of Ethers

41. Chem 36 Ch4. MMUy 29
Step 1

42. Step 2

43. ⚫Williamson Ether Synthesis
This is a good route for synthesis of unsymmetrical ethers
The alkyl halide (or alkyl sulfonate) should be primary to avoid E
2
reaction
Substitution is favored over elimination at lower temperatures

44. Crown Ethers
▪ compounds having structures like that of 18-Crown-6,
a cyclic oligomer of ethylene glycol
▪ named as x-crown-y where x = total number of atoms
in the ring and y = number of oxygen atoms
▪ key property: able to bind cations

45. ▪ Its relationship with the bound ion is called a host-guest
relationship in a mechanism of Lewis acid-base
complex with the oxygen atoms donating their electron
pairs to the central ion.
▪ are called phase-transfer catalysts: they render many
salts soluble in nonpolar solvents by masking the ion
with a hydrocarbon-like exterior
• Use of a crown ether with a nonpolar solvent can favor an
S
N2 reaction since the nucleophile is unencumbered by
the solvent in an aprotic solvent, while at the same time
the cation is prevented by the crown ether from associatin
with the nucleophile.
• Can also be used in oxidation reactions.