CHM122 CCMAS
ALCHOLS
• PROF. OLUGBUYIRO JOSEPH A. O.
7-0
ALCOHOLS
• INTRODUCTION
• Alcohol deals with the chemistry of oxygen-
containing functional group like other important
classes of compounds such as: ethers, aldehydes,
ketones, carboxylic acids, and derivatives of car-
boxylic acids.
• This oxygen-containing functional group is
fundamental to organic chemistry and biochemistry.
1
Functional formula
• Alcohol ROH
• Ether ROR
• Phenol ArOH
2
Structure of Alcohols
• Hydroxyl (OH) functional group
• Oxygen is sp3 hybridized.
=>
3
Classification
• Primary: carbon with –OH is bonded to one other
carbon.
• Secondary: carbon with –OH is bonded to two
other carbons.
• Tertiary: carbon with –OH is bonded to three other
carbons.
• Aromatic (phenol): -OH is bonded to a benzene
ring.
=>
4
Classify these:
CH3 CH3
CH3 CH CH2OH CH3 C OH
CH3
OH OH
CH3 CH CH2CH3 =>
5
Alcohols
NOMENCLATURE
• There are two ways to name alcohols: the systematic,
IUPAC way, and the splendidly vulgar common way.
As usual, these common names are only used for the
smaller members and the IUPAC system takes over as
complexity increases.
• Alcohols are named systematically by dropping the
final "e" of the parent hydrocarbon and adding the
suffix "ol."
6
IUPAC Nomenclature
• Find the longest carbon chain containing the carbon
with the -OH group.
• Drop the -e from the alkane name, add -ol.
• Number the chain, starting from the end closest to
the -OH group.
• Number and name all substituents. =>
7
8
Alcohols are also known by a wide variety of common names,
some of which are given below:
• Examples:
9
Some common names seem to be quite hardy in disappearing e.g.
HO
OH
Prop-2-en-1-ol
Phenol
(Allyl alcohol)
OH
HO
OH OH
OH
Ethane-1,2-diol Propane-1,2,3-triol
(Ethylene glycol Glycerol
10
NOMENCLATURE contd
• Simple alcohols are named as derivatives of the parent
alkane, using the suffix -ol, using the following simple rules:
• Select the longest continuous carbon chain, containing the
hydroxyl group, and derive the parent name by replacing the -
e ending with -ol.
• Number the carbon chain, beginning at the end nearest to the
hydroxyl group.
• Number the substituents and write the name, listing
substituents alphabetically.
11
Some Examples:
12
Name these:
CH3
OH
CH3 CH CH2OH
CH3 CH CH2CH3
2-methylpropan-1-ol
butan-2-ol
CH3 OH
CH3 C OH
CH3
Br CH3
2-methylpropan-2-ol
3-bromo-3-methylcyclohexanol
=>
13
Unsaturated Alcohols
• Hydroxyl group takes precedence. Assign that
carbon the lowest number.
• Use alkene or alkyne name.
OH 4-penten-2-ol (old)
pent-4-ene-2-ol
CH2 CHCH2CHCH3 (1997 revision of IUPAC rules)
=>
14
Naming Priority
• Acids • Alkenes
• Esters • Alkynes
• Aldehydes • Alkanes
• Ketones • Ethers
• Alcohols • Halides
• Amines
=>
7-15
Hydroxy Substituent
• When -OH is part of a higher priority class of
compound, it is named as hydroxy.
• Example:
OH
CH2CH2CH2COOH
4-hydroxybutanoic acid
16
Common Names
• Alcohol can be named as alkyl alcohol.
• Useful only for small alkyl groups.
• Examples:
CH3 OH
CH3 CH CH2OH CH3 CH CH2CH3
isobutyl alcohol sec-butyl alcohol
=>
17
Naming Diols
• Two numbers are needed to locate the two
-OH groups.
• Use -diol as suffix instead of -ol.
HO OH
Hexane-1,6-diol
=>
18
Glycols
• 1, 2 diols (vicinal diols) are called glycols.
• Common names for glycols use the name of the
alkene from which they were made.
CH2CH2 CH2CH2CH3
OH OH OH OH
ethane-1,2-diol Propane-1,2-diol
ethylene glycol propylene glycol
=>
19
Naming Phenols
• -OH group is assumed to be on carbon 1.
• For common names of disubstituted phenols, use
ortho- for 1,2; meta- for 1,3; and para- for 1,4.
• Methyl phenols are cresols.
OH
OH
H3C
4-methylphenol
Cl
3-chlorophenol para-cresol
=>
meta-chlorophenol
20
Physical Properties
• Unusually high boiling points due to hydrogen
bonding between molecules.
• Small alcohols are miscible in water, but solubility
decreases as the size of the alkyl group increases.
=>
21
Acidity of Alcohols
• pKa range: 15.5-18.0 (water: 15.7)
• Acidity decreases as alkyl group increases.
• Halogens increase the acidity.
• Phenol is 100 million times more acidic than
cyclohexanol!
=>
22
Types of Alcohol Reactions
• Dehydration to alkene
• Oxidation to aldehyde, ketone
• Substitution to form alkyl halide
• Reduction to alkane
• Esterification
• Lucas Test
23
Alcohols are Synthetically Versatile
24
Reactions of Alcohols
• DEHYDRATION REACTION
25
i) Dehydration of Alcohols to Yield Alkenes
• The general reaction: forming an alkene from an alcohol
through loss of O-H and H (hence dehydration) of the
neighboring C–H to give bond
• Specific reagents are needed
26
Acid- Catalyzed Dehydration
• Tertiary alcohols are readily dehydrated with acid
• Secondary alcohols require severe conditions (75% H2SO4,
100°C) - sensitive molecules do not survive
• Primary alcohols require very harsh conditions – impractical
• Reactivity is the result of the nature of the carbocation
intermediate
27
Dehydration with POCl3
• Phosphorus oxychloride in the amine solvent pyridine
can lead to dehydration of secondary and tertiary
alcohols at low temperatures
• An E2 reaction via an intermediate ester of POCl2 (see
Figure 17.7)
28
ii) Reduction of Alcohols to Alkanes
• Dehydrate with concentrated H2SO4, then add H2.
• Make a tosylate, then reduce it with LiAlH4.
29
30
Oxidation levels of
oxygen- halogen- and nitrogen-containing
molecules
CH2=CH2 HC CH
CH3CH2OH CH 3CH=O CH 3CO2H
[O] [O] [O]
CH3CH3
CH3CH2Cl CH 3CHCl 2 CH 3CCl3
CH3CH2NH2 CH 3CH=NH CH 3CN
Oxidation
Reduction
31
Oxidation - Reduction
32
Oxidation of 1o Alcohols
33
Oxidation of 2o Alcohols with Cr(VI)
34
Mechanism
Na2Cr2O7 + H2O + 2 H2SO4 2 H2CrO4 + 2 NaHSO 4
OH O OCrO3H
+ HO Cr OH + H2O
o O
2 alcohol Chromic Acid (Cr VI) Chromate ester
CrO3H
O O
+ H3O + HCrO3
OH2
H ketone (Cr IV)
35
Swern Oxidation
• Dimethylsulfoxide (DMSO), with oxalyl chloride
and hindered base, oxidizes 2 alcohols to ketones
and 1 alcohols to aldehydes (same as PCC).
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36
Chapter 11 36
PCC oxidizes 1o Alcohols to Aldehydes
CrO3Cl
N
H PCC
pyridinium chlorochromate
37
Pyridinium Chlorochromate (PCC)
• PCC is a complex of
chromium trioxide,
pyridine, and HCl.
• Oxidizes primary
alcohols to aldehydes.
• Oxidizes secondary
alcohols to ketones.
7-38
Oxidation of 1o Alcohols to
Aldehydes: PCC
39
3° Alcohols Cannot Be Oxidized
• Carbon does not have hydrogen, so oxidation is
difficult and involves the breakage of a C—C bond.
• Chromic acid test is for primary and secondary
alcohols because tertiary alcohols do not react.
Orange color of Cr(VII) turns green - Cr(III); 3o alcohol
is not oxidized, therefore no color change.
40
Sodium Hypochlorite (NaOCl)
• Sodium hypochlorite (household bleach) can oxidize
alcohols without heavy metals or generating
hazardous waste.
• This is a much better option for acid-sensitive
compounds.
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41
Chapter 11 41
Oxidation Summary
CH2CO2H
Na2Cr2O7
H2SO4
NH
CH2CH2OH CH2CHO
CrO3Cl
OO
CH2CHO
DMSO, ClCCCl
(CH3CH2)3N, in CH 2Cl2
42
Reduction Summary
1) LiAlH4 CH2CO2H
+
2) H3O
CH2CH2OH 1) NaBH4 CH2CHO
+
2) H3O
or
CH2CHO
H2, Raney Ni
43
iii)
Reactions Alcohols and Hydrogen Halides
to generate Alkyl Halides
ROH + HX → RX + H2O
44
Reaction of Alcohols with Hydrogen Halides
ROH + HX → RX + HOH
Hydrogen halide reactivity
HI HBr HCl HF
most reactive least reactive
45
Reaction of Alcohols with Hydrogen Halides
ROH + HX → RX + HOH
Alcohol reactivity
R3COH R2CHOH RCH2OH CH3OH
Tertiary Secondary Primary Methanol
most reactive least reactive
46
Preparation of Alkyl Halides
25°C (CH3)3CCl + H2O
(CH3)3COH + HCl
78-88%
OH + HBr
80-100°C + H2O
Br
73%
CH3(CH2)5CH2OH + HBr 120°C
CH3(CH2)5CH2Br + H2O
87-90%
47
Preparation of Alkyl Halides
A mixture of sodium bromide and sulfuric acid may
be used in place of HBr.
NaBr
H2SO4 CH3CH2CH2CH2Br
CH3CH2CH2CH2OH
heat 70-83%
48
Alcohols to Alkyl Halides (Alkyl
Halide formation)
OH HX (HCl or HBr)
X
+ HOH
rapid SN1
o
3 alcohol
HX X
OH + HOH
moderate SN1
o
2 alcohol
49
Mechanism of the Reaction of
Alcohols with Hydrogen
Halides
See previous slides
50
SN1 Mechanism
Step 1: Protonation.
Step 2: Formation of the carbocation.
Step 3: Bromide attacks the carbocation.
51
Solved Problem 2
When 3-methyl-2-butanol is treated with concentrated HBr, the major product is 2-bromo-2-
methylbutane. Propose a mechanism for the formation of this product.
Solution
The alcohol is protonated by the strong acid. This protonated secondary alcohol loses water to form a
secondary carbocation.
52
Lucas Reagent
• Lucas reagent is a solution of anhydrous
zinc chloride (Lewis acid) in concentrated
hydrochloric acid. It is used as a reagent to
test alcohols and classify them in
accordance to their reactivity. The reaction
is a substitution reaction where the
chloride of the zinc chloride gets replaced
by the hydroxyl group of the alcohol.
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53
Chapter 11 53
Lucas Reagent
• The reactivity of the alcohol with
Lucas Reagent is measured by the
degree of turbidity which may vary
from colorless to turbid. The
formation of turbid solution
happens due to the formation of
chloroalkane.
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54
Chapter 11 54
Lucas Test
CH3
CH3
ZnCl 2
CH3COH CH3CCl forms in seconds
12M HCl
CH3 CH + HOZnCl 2
3
CH3 CH3
CH3C OZnCl2 CH3C
Cl
CH3 H CH3
55
SN2 Reaction with the Lucas Reagent
• Primary alcohols react with the Lucas reagent (HCl
and ZnCl2) by the SN2 mechanism.
• Reaction is very slow. The reaction can take from
several minutes to several days.
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56
Chapter 11 56
Qualitative test for Alcohol
Characterization
OH Cl
primary >10 minutes
(if at all)
OH Cl
ZnCl 2, HCl
secondary <5 minutes
OH Cl
tertiary 1-2 seconds
57
Other Simple Qualitative Tests
Br
Br2
Alkenes colorless
reddish-brown
Br
OH O
Alcohols
Na2Cr2O7
green
H2SO4 Cr(IV)
OH orange
Cr(VI) CO2H
58
Intramolecular Dehydration
• A very important reaction by which alcohols can be
converted to alkenes is intramolecular dehydration.
• An equation for such a reaction is shown here:
59
Intramolecular Dehydration
In this reaction the alcohol is heated in the presence of
sulfuric acid. The -OH group on one carbon atom and
the hydrogen atom on an adjacent carbon atom are
split away from the molecule and are essentially
replaced by a double bond. How concentrated the acid
has to be and how hot the mixture has to be heated
depends on the particular alcohol that is being
dehydrated.
60
Alcohol dehydration
Overview:
• The general form of alcohol dehydrations is as
follows:
•
• The first step involves the protonation of the alcohol
by an acid, followed by loss of water to give a
carbocation.
• Elimination occurs when the acid conjugate base
plucks off a hydrogen. Alcohol dehydrations generally
go by the E1 mechanism.
61
Example of alcohol dehydration:
62
Intramolecular Dehydration of
Alcohols
• Alcohol dehydration generally takes place through the E1
mechanism.
• Rearrangements are possible.
• The rate of the reaction follows the same rate as the ease
of formation of carbocations: 3o > 2o > 1o.
• Primary alcohols rearrange, so this is not a good reaction
for converting 1° alcohols into alkenes.
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63
Chapter 11 63
Dehydration of Alcohols – E1
OH
H
H2SO4 (aq) cat.
+ H2 O
H
regenerated
H H HSO 4
O or H2O
-H2O H
64
Methide Shift is Faster than Loss of H+
OH CH3
CH3 CH3
H2SO4 (aq) CH3
CH3 + CH3
distill
+ H2O
major minor
65
Intermolecular Dehydration
• Alcohols can also undergo a reaction known
as intermolecular dehydration in which the H-
comes from one alcohol molecule and the -OH
comes from another alcohol molecule. When that
takes place, a different kind of compound, called
an ether.
66
Intermolecular Dehydration
• If the -OH group comes off of a carbon atom in the first
molecule, that carbon atom will have to form a bond to
something else. Also, if the hydrogen atom in the second
molecule comes off of the oxygen atom, that oxygen atom will
have to form a bond to something else. That carbon atom in
the first molecule bonds to the oxygen atom in the second
molecule and forms a new larger molecule.
• Also, a water molecule is formed by the H- and -OH joining
together.
67
68
Dimerization of Alcohols:
Symmetrical Ethers
Dehydration
o
H2SO4, 125-140 C
2 CH3CH2CH2OH CH3CH2CH2OCH2CH2CH3
+ H2O
69
Mechanism
Dehydration, Acid-Catalyzed
o
H2SO4, 125-140 C
2 CH3CH2CH2OH CH3CH2CH2OCH 2CH2CH3
+ H 2O
H
loss of H2O
CH3CH2CH2-OH CH3CH2CH2OCH2CH2CH3
H 2O H
CH3CH2CH2OH
70
Synthesis/Preparation of Alcohols (Review)
Several methods for preparing alcohols
1. Hydration of alkenes
a) water in acid solution (not very effective)
b) oxymercuration - demercuration
c) hydroboration - oxidation
2. Nucleophilic substitution of OH- on alkyl
halide
=>
71
-Hydration of alkenes
72
-Hydration of alkenes
• More effective ways are:
b) oxymercuration-reduction which leads
to Markovnikov addition
c) hydroboration-oxidation which gives
anti Markovnikov addition
73
Glycols (Review)
• Syn hydroxylation of alkenes
– osmium tetroxide, hydrogen peroxide
– cold, dilute, basic potassium permanganate
• Anti hydroxylation of alkenes
– peroxyacids, hydrolysis
=>
74
Reduction of carbonyl groups.
75
Nucleophilic addition to carbonyl groups
• Overview:
• The general form of the nucleophilic addition to carbonyl
group mechanism is as follows:
• First step is the attack of the nucleophile on the partially
positive carbon to make the tetrahedral intermediate with the
full negatively charged oxygen. The oxygen then becomes
protonated to yield the alcohol.
• Variety of nucleophiles:
• Grignard Reagents
• Alcohols
• Amines
• Alkyl Lithium Reagents
• Acetylide Ions 76
Example of nucleophilic addition to carbonyl groups:
• In this case, acetylide anion is acting as the
nucleophile
77
Preparation of Alcohols
1. Hydration of Alkenes:
• Simple acid-catalyzed hydration of alkenes is a
stepwise reaction involving a carbocation
intermediate. Rearrangements will often occur
and hydroxide anion will bond to the most
stable carbocation center in the molecule
(Markovnikov's Rule).
78
1a) acid-catalyzed hydration of alkenes
• rxns
79
1b) Oxymercuration of Alkenes:
• Oxymercuration of alkenes is a stepwise reaction
involving a bridged mercurinium ion intermediate. In
asymmetrical alkenes, the alkene carbon which
would form the most stable carbocation will bear
more of the positive charge and will be attacked by
hydroxide anion (or water) to give the addition
intermediate;
80
• rearrangements do not occur, but the
orientation follows Markovnikov's Rule.
In a second step, BH4- is used to remove
the mercury and give the final product.
81
1b) Oxymercuration of Alkenes:
82
1c). Formation of 1,2-Diols from Alkenes:
• Reaction of an alkene with MnO4- or OsO4 results in
the formation of a cis-1,2-diol. The reaction involves
the formation of an intermediate cyclic ester, which
decomposes to give the diol. For OsO4, reaction with
HSO3- is necessary to decompose the intermediate
ester and form the final product.
83
1c) Reaction of an alkene with MnO4-
or OsO4 results in the formation of a
cis-1,2-diol
• Rxn:
84
1d) Hydroboration of alkenes
(read up)
85
2. Preparation of Alcohols by Reduction of Aldehydes
and Ketones:
• 2a) Reduction of simple aldehydes and ketones with
BH4- yields the corresponding alcohol directly. The
reaction works well for simple compounds, but
reaction of BH4- with a-b-unsaturated aldehydes and
ketones can result in significant reduction of the
double bond.
86
2. Preparation of Alcohols by Reduction of
Aldehydes and Ketones:
• Rxns
87
2b) A much more powerful reductant is LiAlH4, which will reduce
aldehydes, ketones, esters, carboxylic acids and nitriles. Some sample
reactions are shown below:
• rxns
88
As seen in the first example, the reduction of carboxylate esters results in the
addition of two moles of hydride to the carbonyl carbon, with loss of the
alcohol portion of the ester, forming the corresponding primary alcohol.
• Mechanism
89
3. FURTHER DISCUSION ON Addition of Grignard
Reagents to Carbonyl Compounds
90
Grignard Reagents
• Formula R-Mg-X (reacts like R:- +MgX)
• Stabilized by anhydrous ether
• Iodides most reactive
• May be formed from any halide
– primary
– secondary
– tertiary
– vinyl
– aryl =>
91
Some Grignard Reagents
Br
ether MgBr
+ Mg
Cl MgCl
ether
CH3CHCH2CH3 + Mg CH3CHCH2CH3
CH3C CH2
ether
Br + Mg CH3C CH2 =>
MgBr
92
Organolithium Reagents
-
• Formula R-Li (reacts like R: +Li)
• Can be produced from alkyl, vinyl, or aryl halides, just
like Grignard reagents.
• Ether not necessary, wide variety of solvents can be
used.
=>
93
Reaction with Carbonyl
• R:- attacks the partially positive carbon in the
carbonyl.
• The intermediate is an alkoxide ion.
• Addition of water or dilute acid protonates the
alkoxide to produce an alcohol.
R
C O R C O R C OH
HOH
=> OH
94
Synthesis of 1° Alcohols
Grignard + formaldehyde yields a primary alcohol
with one additional carbon.
CH3 H H CH3 H
H3C C CH2 C MgBr C O CH3 CH CH2 CH2 C O MgBr
H
H H H
CH3 H
HOH
CH3 CH CH2 CH2 C O H
H
=>
95
Synthesis of 2º Alcohols
Grignard + aldehyde yields a secondary alcohol.
CH3 H H3C CH3 CH3
H3C C CH2 C MgBr C O CH3 CH CH2 CH2 C O MgBr
H
H H H
CH3 CH3
HOH
CH3 CH CH2 CH2 C O H
H
=>
96
Synthesis of 3º Alcohols
Grignard + ketone yields a tertiary alcohol.
CH3 H H3C CH3 CH3
H3C C CH2 C MgBr C O CH3 CH CH2 CH2 C O MgBr
H3C
H H CH3
CH3 CH3
HOH
CH3 CH CH2 CH2 C O H
CH3
=>
97
Grignard Reactions
with Acid Chlorides
and Esters
• Use two moles of Grignard reagent.
• The product is a tertiary alcohol with
two identical alkyl groups.
• Reaction with one mole of Grignard reagent
produces a ketone intermediate, which reacts
with the second mole of Grignard reagent.
=>
98
Limitations of Grignard
• No water or other acidic protons like
O-H, N-H, S-H, or -C—C-H. Grignard reagent is
destroyed, becomes an alkane.
• No other electrophilic multiple bonds, like C=N, C—
N, S=O, or N=O.
=>
99
Formation of Phenoxide Ion
Phenol reacts with hydroxide ions to form
phenoxide ions - no redox is necessary.
O H O
+ OH
+ HOH
pKa = 15.7
pKa = 10
=>
100
