HYDROXYL COMPOUNDS

1
Alcohols and Phenols
Alcohols contain an OH group connected to a a
saturated C (sp
3
)
They are important solvents and synthesis intermediates
Methanol, CH
3
OH, called methyl alcohol, is a common
solvent, a fuel additive, produced in large quantities
Ethanol, CH
3
CH
2
OH, called ethyl alcohol, is a solvent, fuel,
beverage
Phenols contain an OH group connected to a carbon
in a benzene ring
Phenol, C
6
H
5
OH (phenyl alcohol) has diverse uses - it
gives its name to the general class of compounds
2
Naming Alcohols
General classifications of alcohols based
on substitution on C to which OH is
attached
Methyl (C has 3 Hs), Primary (1) (C has
two Hs, one R), secondary (2) (C has
one H, two Rs), tertiary (3) (C has no H,
3 Rs),
3
IUPAC Rules for Naming Alcohols
Select the longest carbon chain containing the hydroxyl
group, and derive the parent name by replacing the -e
ending of the corresponding alkane with -ol
Number the chain from the end nearer the hydroxyl
group
Number substituents according to position on chain,
listing the substituents in alphabetical order
4
Properties of Alcohols and
Phenols: Hydrogen Bonding
The structure around O of the alcohol or phenol is similar
to that in water, sp
3
hybridized
Alcohols and phenols have much higher boiling points
than similar alkanes and alkyl halides
5
Alcohols Form Hydrogen Bonds
A positively polarized OH hydrogen atom from one molecule is
attracted to a lone pair of electrons on a negatively polarized oxygen
atom of another molecule
This produces a force that holds the two molecules together
These intermolecular attractions are present in solution but not in
the gas phase, thus elevating the boiling point of the solution
6
Properties of Alcohols and
Phenols: Acidity and Basicity
Weakly basic and weakly acidic
Alcohols are weak Brnsted bases
Protonated by strong acids to yield oxonium ions, ROH
2
+

7
Alcohols and Phenols are Weak
Brnsted Acids
Can transfer a proton to water to a very
small extent
Produces H
3
O
+
and an alkoxide ion, RO

,
or a phenoxide ion, ArO

8
pK
a
Values for Typical OH
Compounds
9
Generating Alkoxides from
Alcohols
Alcohols are weak acids requires a strong base to form
an alkoxide such as NaH, sodium amide NaNH
2
, and
Grignard reagents (RMgX)
Alkoxides are bases used as reagents in organic
chemistry
10
Phenol Acidity
Phenols (pK
a
~10) are much more acidic than alcohols
(pK
a
~ 16) due to resonance stabilization of the
phenoxide ion
Phenols react with NaOH solutions (but alcohols do not),
forming soluble salts that are soluble in dilute aqueous
A phenolic component can be separated from an organic
solution by extraction into basic aqueous solution and is
isolated after acid is added to the solution
11
Nitro-Phenols
Phenols with nitro groups at the ortho and para
positions are much stronger acids
The pKa of 2,4,6-trinitrophenol is 0.6, a very
strong acid
12
Preparation of Alcohols
Alcohols are derived from many types of compounds
The alcohol hydroxyl can be converted to many other
functional groups
This makes alcohols useful in synthesis
13
Preparation of Alcohols by
Regiospecific Hydration of Alkenes
Hydroboration/oxidation: syn, non-Markovnikov hydration
Oxymercuration/reduction: Markovnikov hydration
14
Alcohols from Reduction of
Carbonyl Compounds
Reduction of a carbonyl compound in general gives an
alcohol
Note that organic reduction reactions add the equivalent
of H
2
to a molecule
15
Reduction of Aldehydes and
Ketones
Aldehydes gives primary alcohols
Ketones gives secondary alcohols
16
Reduction Reagent: Sodium
Borohydride
NaBH
4
is not sensitive to moisture and it does not
reduce other common functional groups
Lithium aluminum hydride (LiAlH
4
) is more powerful, less
specific, and very reactive with water
Both add the equivalent of H

17
Mechanism of Reduction
The reagent adds the equivalent of hydride to
the carbon of C=O and polarizes the group as
well
18
Reduction of Carboxylic Acids and
Esters
Carboxylic acids and esters are reduced to give primary
alcohols
LiAlH
4
is used because NaBH
4
is not effective
19
Alcohols from Reaction of Carbonyl
Compounds with Grignard Reagents
Alkyl, aryl, and vinylic halides react with magnesium in
ether or tetrahydrofuran to generate Grignard reagents,
RMgX
Grignard reagents react with carbonyl compounds to
yield alcohols
20
Examples of Reactions of Grignard
Reagents with Carbonyl Compounds
21
Mechanism of the Addition of a
Grignard Reagent
Grignard reagents act as nucleophilic carbon anions
(carbanions, : R) in adding to a carbonyl group
The intermediate alkoxide is then protonated to produce
the alcohol
22
Reactions of Alcohols
Two general classes of reaction
At the carbon of the CO bond
At the proton of the OH bond
23
REACTION OF ALCOHOLS WITH
SODIUM METAL (Acidic reaction)
R OH + Na (s) RO
-
Na
+
+
1/2 H
2
OH
+ Na
O
-
Na
+
+ 1/2H
2
sodium phenoxide
H
3
C
OH
+
Na
O
-
Na
+
+
1/2H
2
propanol
sodium propoxide
H
3
C
OH
+
NaH
O
-
Na
+
+
H
2
propanol
sodium propoxide
sodium hydride
24
REACTION OF ALCOHOLS WITH
ACID (basic reaction)
The oxygen center can donate electron
density and this causes the alcohols basic
nature. Acts as Lewis bases especially for
tertiary alcohols
Me OH +
HBr
Me O
+
H
H
Br
-
25
Dehydration of Alcohols to Alkenes
The general reaction: forming an alkene from an alcohol
through loss of O-H and H (hence dehydration) of the
neighboring CH to give bond
Specific reagents are needed
26
Acid- Catalyzed Dehydration
Tertiary alcohols are readily dehydrated with acid
Secondary alcohols require severe conditions (75%
H
2
SO
4
, 100C) - sensitive molecules don't survive
Primary alcohols require very harsh conditions
impractical
Reactivity is the result of the nature of the carbocation
intermediate
27
Conversion of Alcohols into Alkyl
Halides
3 alcohols are converted by HCl or HBr at low
temperature
1 and alcohols are resistant to acid use SOCl
2

or PBr
3
by an S
N
2 mechanism
28
Oxidation of Alcohols
Can be accomplished by inorganic reagents, such as
KMnO
4
, CrO
3
, and Na
2
Cr
2
O
7
or by more selective,
expensive reagents
29
Oxidation of Primary Alcohols
To aldehyde: pyridinium chlorochromate (PCC,
C
5
H
6
NCrO
3
Cl) in dichloromethane
Other reagents produce carboxylic acids
30
Oxidation of Secondary
Alcohols
Effective with inexpensive reagents such as
Na
2
Cr
2
O
7
in acetic acid
PCC is used for sensitive alcohols at lower
temperatures
31
Mechanism of Chromic Acid
Oxidation
Alcohol forms a chromate ester followed by elimination
with electron transfer to give ketone.
32
ESTERIFICATION
Alcohols react with carboxylic acids/acid
chlorides to form esters
RCOOH + R'OH RCOOR' + H
2
O
H
3
C O
H
O
+ CH
3
CH
2
OH
H
3
C O
CH
2
CH
3
O
+ H
2
O
ethyl ethanoate ethanoic acid
ethanol
O
H
O
+
CH
3
OH
O
CH
3
O
methyl benzoate benzoic acid
H
3
C Cl
O
+ CH
3
CH
2
OH
H
3
C O
CH
2
CH
3
O
ethyl ethanoate ethanoil chloride
ethanol
33
PHENOLS
Not exactly the same as alcohols because
the lone pair on oxygen and the ring
system are in conjugation
Increases the electron density in the ring
activating it towards electrophilic
substitution (ortho and para positions)
Also decreases the bond strength of O-H
making it more acidic than alcohols
34
Synthesis of phenol
From diazonium salts

CH
3
NH
2
NaNO
2
/H
2
SO
4
0
0
C
CH
3
N
2
+
heat
H
2
O
CH
3
OH
Draw the mechanism of the reaction?
35
Synthesis of phenols
Hydrolysis of chlorobenzene

Cl
1. NaOH, H
2
O, 370
0
C
2. H
3
O
+
OH
36
Reactions of Phenols
OH group is acidic
O is nucleophilic O-acylation and O-
alkylation
Can be oxidised to quinones
Electrophloic substitution at the ring
37
Reactions of phenols
O-alkylation and O-acylation; formation of
ethers and esters
OH
acid or base cat.
O
O O
O
O
ester
OH
NaH
or NaOH
O
-
R-X
O R
ether
38
Reaction with diazomethane-
formation of methyl esters
Diazomethane can be used to methylate phenols
The acidic OH proton is first removed to give diazomethane to
give methyl diazonium ion which is then attacked by the
phenoxide ion
O
H
H
2
C N N diazomethane H
3
C N N
O
O
CH
3
+ N
2
39
Electrophilic substitutions
Phenols react very rapidly with
electrophiles at the ring because the
oxygen atom can donate electron density
to the ring making it electron rich. This
activates the ring towards electrophilic
substitution
Substitutions occur at the ortho and para
positions
40
Examples
OH
E
+
OH
E
+
OH
E
OH
HNO
3
/acetic acid
OH
NO
2
CH
3
CH
3
OH
OH
H
2
SO
4
100
0
C
SO
3
H
nitration
sulphonation
OH
OH
(CH
3
)
3
COH
phosporic acid. 60
0
C
Friedel-Crafts reaction
41
Oxidation of phenols
Phenols can be oxidised to give 1,4-quinone
(para-quinone)
OH
H
2
CrO
4
O
O
mechanism:
O
CrO
3
H
H
2
O
-H
+
O
HO H
OH
OH
H
2
CrO
4
O
CrO
3
H
O
H
42
Oxidation of phenols
Oxidation of dihydroxyarenes
OH
OH
Ag
2
O
O
O
OH
OH
O
O
Ag
2
O
43
Riemer-Tiemann Reaction
Conversion from phenol to 2-
hydroxybenzaldehyde using chloroform and
base
OH
CHCl
3
/NaOH
OH
C
H
O
mechanism:
O
-
CHCl
2
CCl
2
H
O
O
-
C
Cl
H
Cl
O
Cl
H
H
2
O
O
-
O
Cl
H
H
OH
C
H
O
44
Ethers
45
Ethers and Their Relatives
An ether has two organic groups (alkyl, aryl, or vinyl)
bonded to the same oxygen atom, ROR

Diethyl ether is used industrially as a solvent

Tetrahydrofuran (THF) is a solvent that is a cyclic ether

Epoxides contain a C-O-C unit which make-up a three
membered ring

Thiols (RSH) and sulfides (RSR) are sulfur (for
oxygen) analogs of alcohols and ethers
46
47
Naming Ethers
Ethers are named two ways:

As alkoxy derivatives of alkanes

Derived by listing the two alkyl groups in the general
structure of ROR in alphabetical order as separate
words and adding the word ether
When both alkyl groups are the same, the prefix di-
precedes the name of the alkyl group
(Ethers can be described as symmetrical or
unsymmetrical)
48
Naming Ethers
CH
3
CH
2
O CH
2
CH
3
Diethyl ether
Ethoxyethane
CH
3
CH
2
O CH
3
Ethyl methyl ether
Methoxyethane
CH
3
CH
2
O CH
2
CH
2
CH
2
Cl
3-Chloropropyl ethyl ether
1-Chloro-3-ethoxypropane
49
Naming Ethers
Epoxides (oxiranes)
epoxy always
preceeds the name of
the alkane
O
1,2-Epoxycyclohexane
O
2-Methyl-2,3-epoxybutane
50
Example 1: Name
51
1
2
3
4
5
6
7
8
O
O
O
Br
O
Br Cl
Br OCH
3
OCH
3
O
O
1
2
3
4
5
6
7
8
O
O
O
Br
O
Br Cl
Br OCH
3
OCH
3
O
O
Example 2: Draw
1. Isopropyl methyl ether

2. 4-t-butoxy-1-cyclohexene

3. Phenyl propyl ether

4. O- nitro anisole


52
Structure, Properties and Sources
of Ethers
ROR ~ tetrahedral bond angle (112 in
dimethyl ether)

Oxygen is sp
3
-hybridized

Oxygen atom gives ethers a slight dipole
moment (diethyl ether 1.2 D)
53
Structure, Properties, and Sources of
Ethers (comparative boiling points)
CH
3
CH
2
OCH
2
CH
3
Diethyl ether
bp =35
o
C
solubility in water: 7.5 g/100mL
CH
3
CH
2
CH
2
CH
2
CH
3
Pentane
bp =36
o
C
solubility in water: insoluble
CH
3
CH
2
CH
2
CH
2
OH
1-Butanol
bp =117
o
C
solubility in water: 9 g/100mL 54
Preparation of Ethers
1. Acid catalyzed synthesis of ethers
H
2
SO
4
Dibutyl ether
130
o
C
OH
2
butanol
O
+ H
2
O
Limited to symmetrical ethers
55
Mechanism 1: Acid catalyzed
synthesis of ethers
56
2
130 C
H---Cl
H3O
+
Cl
-
H3O
+
Cl
-
OH O
OH O
+
H
H O
H
O
+
H
O
H H
O
HCl
+
+
+
+
2
130 C
H---Cl
H3O
+
Cl
-
H3O
+
Cl
-
OH O
OH O
+
H
H O
H
O
+
H
O
H H
O
HCl
+
+
+
+
Preparation of Ethers
2. Williamson ether synthesis
Metal alkoxides react with primary alkyl halides by an
S
N
2 pathway to yield ethers.

Secondary and tertiary substrates react following an
E2 mechanism

57
Mechanism 2: Williamson Ether
Synthesis
58
NaH
THF
CH3CH2----I
THF
H2
Na
+
H
-
NaI
H2
CH3CH2----I
NaI
THF
Na
+
Na
+
OH O

O
O

O
H
O
+
+
+
+
+
+
NaH
THF
CH3CH2----I
THF
H2
Na
+
H
-
NaI
H2
CH3CH2----I
NaI
THF
Na
+
Na
+
OH O

O
O

O
H
O
+
+
+
+
+
+
Example 3: Williamson ether
synthesis
O
+
CH
3
CH
2
Br
S
N
2
?
Br
CH
3
CH
2
O
E2
?
+
59
Example 4
How would you prepare the following
compounds using a Williamson synthesis?

Methyl propyl ether


Anisole (methyl phenyl ether)


60
Example 5: Predict the product
+
Br
CH
3
CH
2
CHCH
3
O
61
Preparation of Ethers
3. Alkoxymercuration of alkenes

React alkene with an alcohol and mercuric
acetate or trifluoroacetate

Demercuration with NaBH
4
yields an ether

Overall Markovnikov addition of alcohol to
alkene
62
63
64
Reactions of Ethers: Acidic Cleavage
Ethers are generally unreactive

Strong acid will cleave an ether at elevated
temperature

HI, HBr produce an alkyl halide from less
hindered component by S
N
2 (tertiary ethers
undergo S
N
1)
65
66
Mechanism 3: Acidic Cleavage
67
Note that the halide attacks the protonated ether at
the less highly substituted site
Example 6
68
Reactions of Ethers: Claisen
Rearrangement
Specific to allyl aryl ethers, ArOCH
2
CH=CH
2

Heating to 200250C leads to an o-allylphenol
Result is alkylation of the phenol in an ortho position
69
Mechanism 4: Claisen
Rearrangement
Concerted pericyclic 6-electron, 6-membered
ring transition state
Mechanism consistent with
14
C labeling
70