Alcohol

1
Chapter 17

• Alcohol Phenol
• ROH ArOH

2
Chapter 17

• Naming
• Properties
• Synthesis
• Reactions

3
5-methyl-2,4-hexanediol
4
2-methyl-4-phenyl-2-butanol
5
4,4-Dimethylcyclohexanol
6
trans-2-Bromocyclopentanol
7
4-Bromo-3-methyl-phenol
8
2-(2-Hydroxyethyl)phenol
o-(2-Hydroxyethyl)phenol
9
Chapter 17

• Naming
• Properties
• Synthesis
• Reactions

10
Properites

• Hydrogen bonding
• Acidity and Basicity

11
Hydrogen Bonding
H2O
HF
H2Te
NH3
H2Se
H2S
SnH4
extrapolation
GeH4
SiH4
CH4
1. Water, HF, and NH3 show unusually high bp.
2. Dotted lines depict bp if there were no
H-bonding.
3. All others follow normal trend.
12
Hydrogen Bonding in Water
?
?
?
?
?--
?--
?
?
?--
?
?
?
?--
?
?--
13
Hydrogen Bonding in Alcohol
?
?
?-
?-
?
?-
?
?
?-
?-
14
Hydrogen Bonding and Boiling Point
15
Properites

• Hydrogen bonding
• Acidity and Basicity

16
Acidity Basicity
Like water, alcohol can act as an acid or as a
base.
base
acid
oxonium ion
alkoxide ion
acid
base
phenoxide ion
17
1. Why does the reaction shift to the right?
2. Why is phenoxide ion stable?
3. Why is phenol acidic (compare to water)?
.
18
Resonance, Stability, Acid Strength
1. Resonance structures implies stability.
3. Stable anion also implies that phenol is a
stronger acid than water.
19
Substituted Phenol
Which one is more acidic and why?
20
To examine the acid strength,
21
Resonance, Stability, Acid Strength
2. Fifth structure shows that nitro is an
electron-withdrawing group.
5. See page 663 for para position effect.
22
Resonance, Stability, Acid Strength
1. Phenol is more acidic than p-methylphenol.
2. pKa indicates that CH3 is an
electron-donating group.
23
Arrange the order of acidity (from highest to
lowest) of the following compounds and explain
why.
24
Answer Key
4-methoxylphenol (least acidic)
phenol
4-nitrobenzylphenol (most acidic)
Reason The nitro- on 4-nitrobenzylphenol is an
electron-withdrawing group which enhances the
aciditiy compare to phenol. The methoxy-
of 4-methoxylphenol is an electron-donating
group, thus it is less acidic than phenol.
25
Chapter 17

• Naming
• Properties
• Synthesis
• Reactions

26
Synthesis

• Hydroboration, Oxymercuration, Hydroxylation.
• Reaction with peroxide.
• Reduction of carbonyl compounds.

27
M
halogenation
anti
halohydrination
oxidation
M
anti
oxymercuration
M
oxidation
Alkene
hydroboration
non-M
syn
Simmons-Smith
syn
hydrogenation
syn
carbenation
syn
syn
hydroxylation
28
Synthesis

• Hydroboration, Oxymercuration, Hydroxylation.
• Reaction with peroxide.
• Reduction of carbonyl compounds.

29
Also from alkene
1-Methyl-1,2-epoxy- cyclohexane
1-Methyl- trans-1,2-cyclohexanol
30
Synthesis

• Hydroboration, Oxymercuration, Hydroxylation.
• Reaction with peroxide.
• Reduction of carbonyl compounds.

31
Reduction of Aldehyde Ketone
Reducing Agents
1. NaBH4, ethanol, H 2. LiAlH4, ether, H
32
Reduction of Carboxylic Acid Ester
Reducing Agents
LiAlH4, ether, H
33
Carbonyl compounds Grignard reagent
34
Chapter 17

• Naming
• Properties
• Synthesis
• Reactions

35
Reactions

• Dehydration ? alkenes
• With HX ? alkyl halides
• With Tosylates
• Oxidation - 1o, 2o, 3o
• Protection of alcohol

36
Synthesis of Alkene
From halides - dehydrohalogenation (minus HX)
Elimination
From alcohol - dehydration (minus H2O)
Chapter 7 slide 5
37
Dehydration
1. Watch for Zaitsevs rule!!!
2. Only 3o alcohols are readily dehydrated with
acid.
3. 2o alcohols are dehydrated under mild basic
condition.
4. Alcohol dehydration via E2.
38
Dehydration Mechanism
E1
39
Reactions

• Dehydration ? alkenes
• With HX ? alkyl halides
• With Tosylates
• Oxidation - 1o, 2o, 3o
• Protection of alcohol

40
Alcohol to Alkyl Halide
SN2
41
Reactions

• Dehydration ? alkenes
• With HX ? alkyl halides
• With Tosylates
• Oxidation - 1o, 2o, 3o
• Protection of alcohol

42
p-toluenesulfonyl Chloride (p-TosCl)
ROTos
43
With Tosylate
CO broken
Inversion
Inversion
R
S
R
CO not broken
No inversion
Inversion
S
R
R
44
Reactions

• Dehydration ? alkenes
• With HX ? alkyl halides
• With Tosylates
• Oxidation - 1o, 2o, 3o
• Protection of alcohol

45
Oxidation - Primary Alcohol
46
Oxidation - Secondary Alcohol
47
Oxidation - Tertiary Alcohol
No Reaction
48
Reactions

• Dehydration ? alkenes
• With HX ? alkyl halides
• With Tosylates
• Oxidation - 1o, 2o, 3o
• Protection of alcohol

49
Protection of Alcohol
It often happens, particularly during synthesis
of complex molecules, that one functional group
in a molecule interferes with an intended
reaction on a second functional group elsewhere
in the same molecule. - p 682.
50
Trimethylsilyl (TMS) ether
Chlorotrimethylsilane
TMS ether
ROH is now blocked or protected!!!
51
Step 1 Adding Protection Group

52
Step 2a Carrying Out Reaction
53
Step 2b Carrying Out Reaction

54
Step 3 Removing Protection Group