Organic Chemistry Fifth Edition

1
Chapter 4
Alcohols and Alkyl Halides
Jozsef Devenyi Department of Chemistry, UT Martin
2
Coverage of the chapter
- chemical reactions and their mechanisms
- focus on two reactions that yield alkyl halides
(1) alcohol hydrogen halide ROH
HX ? RX H2O
(2) alkane halogen R-H X2 ?
R-X H-X
Both are substitution reactions
3
IUPAC Nomenclature of Alkyl Halides
The two most widely used IUPAC nomenclature
systems
- functional class nomenclature
- substitutive nomenclature
4
IUPAC Nomenclature of Alcohols
Number chain in direction that gives lowest
numberto the carbon that bears the OH group.
5
Classification
Alcohols and alkyl halides are classified as
primary secondary
tertiary
according to their "degree of substitution."
Degree of substitution is determined by
countingthe number of carbon atoms directly
attached tothe carbon that bears the halogen or
hydroxyl group.
6
Bonding in Alcohols and Alkyl Halides
alcohols and alkyl halides are polar
Dipole Moments
?

H
?
?
?
?
? 1.9 D
? 1.7 D
H
H
?? ?
?? ?
?? ?
?? ?
? ??
7
Physical Properties of Alcohols and Alkyl Halides
Intermolecular Forces
Boiling point Solubility in water
Density
Effect of Structure on Boiling Point
CH3CH2CH3
CH3CH2OH
CH3CH2F
Molecularweight Boilingpoint,
C Dipolemoment, D
44 48 46
- 42 - 32 78
0 1.9 1.7
8
Bonding in Alcohols and Alkyl Halides
Effect of Structure on Boiling Point
CH3CH2CH3
Molecularweight Boilingpoint,
C Dipolemoment, D
Intermolecular forcesare weak. The only
intermolecular forces are induced dipole-induced
dipole attractions.
44 - 42 0
9
Bonding in Alcohols and Alkyl Halides
Effect of Structure on Boiling Point
CH3CH2F
Molecularweight Boilingpoint,
C Dipolemoment, D
A polar moleculetherefore dipole-dipoleand
dipole-induceddipole forces contributeto
intermolecular attractions.
48 - 32 1.9
10
Bonding in Alcohols and Alkyl Halides
Effect of Structure on Boiling Point
CH3CH2OH
Molecularweight Boilingpoint,
C Dipolemoment, D
Highest boiling pointstrongest
intermolecularattractive forces. Hydrogen
bonding isstronger than other dipole-dipole
attractions.
46
78
1.7
11
Bonding in Alcohols and Alkyl Halides
Effect of Structure on Boiling Point
Hydrogen bonding in ethanol
?
?
?
?
12
Bonding in Alcohols and Alkyl Halides
Boiling point increases with increasing number of
halogens
Compound Boiling Point

• CH3Cl - 24C
• CH2Cl2 40C
• CHCl3 61C
• CCl4 77C

Even though CCl4 is the only compound in this
list without dipole moment, it has the highest
boiling point.
Induced dipole-induced dipole forces are greatest
in CCl4 because it has the greatest number of Cl
atoms. Cl is more polarizable than H.
13
Bonding in Alcohols and Alkyl Halides
But trend is not followed when halogen is
fluorine.
Compound Boiling Point
CH3CH2F - 32C CH3CHF2 - 25C CH3CF3 -
47C CF3CF3 - 78C
Reasons

• fluorine is not very polarizable

• the induced dipole - induced dipole forces
• decrease with increasing fluorine substitution

14
Bonding in Alcohols and Alkyl Halides
Solubility in water
- Alkyl halides are insoluble in water.
- Methanol, ethanol, isopropyl alcohol are
completely miscible with water.
- The solubility of an alcohol in water
decreases with increasing number of carbons
(compound becomes more hydrocarbon-like).
15
Bonding in Alcohols and Alkyl Halides
Hydrogen Bonding Between Ethanol and Water
16
Bonding in Alcohols and Alkyl Halides
Density
- Alkyl fluorides and alkyl chlorides are less
dense than water.
- Alkyl bromides and alkyl iodides are more
dense than water.
- All liquid alcohols have densities of about 0.8
g/mL.
17
Acids and Bases General Principles A Review
Recall acid-base theories from General Chemistry
- strength of acidity (Ka, pKa values)
- memorize Table 4.2 for relative acid strength
( 5 accuracy for pKa values)
18
Acids and Bases General Principles A Review
Example
19
Proton Transfer Reactions Mechanism
20
Proton Transfer Reactions Mechanism
21
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Reaction of Alcohols with Hydrogen Halides
ROH HX ? RX HOH
- Hydrogen halide reactivity HF HCl HBr HI
most reactive
least reactive
- Alcohol reactivity CH3OH
RCH2OH R2CHOH R3COH
methanol primary secondary
tertiary
most reactive
least reactive
22
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Examples of reactions
25C
(CH3)3CCl H2O
(CH3)3COH HCl
78-88
23
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
- A mechanism describes how reactants are
converted to products step by step.
- Mechanisms are often written as a series of
chemical equations showing the elementary steps.
- An elementary step is a reaction that proceeds
by way of a single transition state.
- Mechanisms can be shown likely to be correct,
but cannot be proven correct.
24
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
For the reaction
the generally accepted mechanism involves three
elementary steps
- Step 1 protonation of alcohol oxygen
(Brønsted acid-base reaction)
- Step 2 carbocation formation
(breakage of C-O bond in alcohol onium ion)
- Step 3 carbocation capture by Cl-
(Cl- attacks carbocation)
25
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Like proton transferfrom a strong acid towater,
proton transferfrom a strong acid toan alcohol
is normallyvery fast.
Mechanism of reactions
Two molecules reactin this elementarystep
therefore it is bimolecular.
26
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
Potential energy diagram for Step 1
(CH3)3COH HCl

27
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
Step 2 Carbocation formation
Dissociation of the alkyloxonium ion involves
bond- breaking, withoutany bond-making to
compensate for it. It has a high activation
energy and is slow.
28
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
Step 2 Carbocation formation
A single moleculereacts in this steptherefore,
it isunimolecular.
29
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
Potential energy diagram for Step 2

30
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
Carbocation
- positively charged carbon is sp2-hybridized

• key intermediate in rxn of 2o and 3o
• alcohols with HX
• is a carbocation

• all four carbons in
• same plane

- unhybridized p orbital is perpendicular to
plane of four carbons.

• a cation with center carbon with 6 valence
• e- and a () charge

31
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
Bond formation between the positively charged
carbocation and the negatively charged chloride
ion is fast.
Step 3 Carbocation capture


(CH3)3C
fast, bimolecular
..
Two species are involved in this
step.Therefore, this stepis bimolecular.
tert-butyl chloride
32
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
This is a Lewis acid-Lewis base reaction.The
carbocation is theLewis acid chlorideion is
the Lewis base.
Step 3 Carbocation capture


(CH3)3C
fast, bimolecular
The carbocation is an electrophile. Chloride ion
is anucleophile.
..
tert-butyl chloride
33
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
Step 3 Carbocation capture
34
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanism of reactions
Potential energy diagram for Step 3
carbocation capture

(CH3)3CCl
35
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Potential Energy Diagrams for Multistep Reactions
- The potential energy diagram for a multistep
mechanism is simply a collection of the
potential energy diagrams for the individual
steps.
- Consider the three-step mechanism for the
reaction of tert-butyl alcohol with HCl.
36
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37
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanistic notation
The mechanism just described is an example of an
SN1 process.
SN1 stands for substitution-nucleophilic-unimolec
ular.
The molecularity of the rate-determining step
defines the molecularity of the overall reaction.
38
Preparation of Alkyl Halides from Alcohols and
Hydrogen Halides
Mechanistic notation
The molecularity of the rate-determining step
defines the molecularity of the overall reaction.
Rate-determining step is unimolecular
dissociation of alkyloxonium ion.
39
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41
Structure, Bonding, and Stability of Carbocations
Carbocations
- Most carbocations are too unstable to be
isolated, but occur as reactive intermediates
in a number of reactions.
Can all these types of carbocations form in a
rxn? (i.e., all of them stable enough to be
allowed to form?)
42
Structure, Bonding, and Stability of Carbocations
Carbocations
- the different types of carbocations have
different stabilities
- order of carbocation stability
- the more alkyl groups attached to positively-
charged carbon the more stable carbocation is
- reason behind varying carbocation stability
different degrees of
inductive effect
positively chargedcarbon pullselectrons in ?
bondscloser to itself

43
Structure, Bonding, and Stability of Carbocations
Carbocations
as a result, positive charge is "dispersed ",
i.e., shared by carbon and the three atoms
attached to it
??
??
electrons in CC bonds are more polarizable than
those in CH bonds therefore, alkyl groups
stabilize carbocations better than H.
??
??
Electronic effects transmitted through ??bonds
are called "inductive effects."
44
Effect of Alcohol Structure on Reaction Rate
slowest step of rxn ROH HX
Recall
RX H2O

is
R

- the more stable the carbocation, the faster it
forms
- since order of carbocation stability is
therefore, 3o alcohols react faster than 2o,
which react faster than 1o, which react faster
than methanol
45
Effect of Alcohol Structure on Reaction Rate
Why?
very high Ea for formation of methyl cation
high Ea for formation of 1o carbocation
46
Effect of Alcohol Structure on Reaction Rate
Eact
lower Ea for formation of 2o carbocation
lowest Ea for formation of 3o carbocation
47
Reaction of Primary Alcohols with Hydrogen Halides
Recall examples of reactions
25C
(CH3)3CCl H2O
(CH3)3COH HCl
78-88
48
Reaction of Primary Alcohols with Hydrogen Halides
- 1o carbocations are too high in energy to
allow for SN1 mechanism. Yet, 1o alcohols are
converted to alkyl halides.
120C
CH3(CH2)5CH2OH HBr
CH3(CH2)5CH2Br H2O
87-90
- therefore, 1o alcohols have to react through
a different type of mechanism to give 1o alkyl
halides
- 1o alcohols react by (substitution-nucleop
hilic-bimolecular)
SN2 mechanism
49
Reaction of Primary Alcohols with Hydrogen Halides
SN2 mechanism
a two-step mechanism for conversion of alcohols
to alkyl halides

• proton transfer to alcohol to form alkyloxonium
• 
  ion

• bimolecular displacement of water from
• alkyloxonium ion by halide

Example
120C
CH3(CH2)5CH2OH HBr
CH3(CH2)5CH2Br H2O
87-90
50
Reaction of Primary Alcohols with Hydrogen Halides
SN2 mechanism
Step 1 H transfer from HBr to
1-heptanol
..
..



..
H
51
Reaction of Primary Alcohols with Hydrogen Halides
SN2 mechanism
Step 2 rxn of alkyloxonium ion
with bromide ion

52
Reaction of Primary Alcohols with Hydrogen Halides
SN2 mechanism
53
Other Methods for Converting Alcohols to Alkyl
Halides
For 1o and 2o alkyl halide preparations
alternative ways are also available
ROH SOCl2
R-Cl HCl
1. thionyl chloride
2. phosphorus tribromide
3 ROH PBr3
3R-Br 3H3PO3
3. phosphorus, iodine
P
ROH I2
R-I
(these three rxns occur via SN2 mechanism)
54
Other Methods for Converting Alcohols to Alkyl
Halides
Examples
SOCl2
CH3CH(CH2)5CH3
CH3CH(CH2)5CH3
K2CO3
Cl
(81)
OH
PBr3
(CH3)2CHCH2OH
(CH3)2CHCH2Br
(55-60)
55
Halogenation of Alkanes
Another way to prepare R-X alkane
halogen
free-radical halogenation of alkanes
RH X2 ? RX HX
Energetics

• - explosive for F2
• - exothermic for Cl2 and Br2
• - endothermic for I2

Example
chlorination of methane
hn or D
a free-radical chain reaction
CH4 X2 CH3Cl HCl
56
Halogenation of Alkanes

• rxn proceeds through a new type of mechanism

• free-radicals form during reaction

free-radicals atoms, groups of atoms with
unpaired electron
(typically neutral radicals)
..
Examples
NO
Structure and Stability of Free Radicals

• most alkyl free-radicals in which carbon bears
  the
• unpaired electron are too unstable to be
  isolated

• alkyl free-radicals are classified as 1o , 2o
  or 3o
• in the same way that carbocations are

57
Halogenation of Alkanes
Structure and Stability of Free Radicals

• stability of alkyl free-radicals follow
  stability order
• of carbocations

methyl free-radical - planar, - central carbon
is sp2-hybridized - unpaired electron is in a p
orbital

• The order of stability of free radicals can be
• determined by measuring bond strengths.

58
Halogenation of Alkanes
Structure and Stability of Free Radicals

• By "bond strength" we mean the energy required
  to break a covalent bond.

• A chemical bond can be broken in two different
• waysheterolytically or homolytically.

two e- inthe bond divided equally
Homolytic



Heterolytic
one atom retains both e-

59
Halogenation of Alkanes
Structure and Stability of Free Radicals
The species formed by a homolytic bond
cleavageof a neutral molecule are free radicals.
Therefore, measure energy cost of homolytic
bond cleavage to gain information about
stability of free radicals.
The more stable the free-radical products, the
weaker the bond, and therefore the lower the
bond-dissociation energy.
For example, bond-dissociation energy
measurements tell us that isopropyl free-radical
is 13 kJ/mol more stable than propyl
free-radical.
60
Halogenation of Alkanes
Structure and Stability of Free Radicals
CH3CH2CH3
61
Halogenation of Alkanes
Structure and Stability of Free Radicals
Also, bond-dissociation energy measurements tell
us that tert-butyl radical is 30 kJ/mol more
stable than isobutyl.
.
(CH3)2CHCH2 H
.
410
380
(CH3)3CH
62
Halogenation of Alkanes
Mechanism of chlorination of methane
hn or D
a free-radical chain reaction
CH4 X2 CH3Cl HCl
Mechanism
stage 1 initiation
stage 2 propagation
stage 3 termination
Stage 1 initiation
"gets the reaction going"
63
Halogenation of Alkanes
Mechanism of chlorination of methane
Stage 2 propagation
each step consumes one free-radical but
generates another one
64
Halogenation of Alkanes
Mechanism of chlorination of methane
65
Halogenation of Alkanes
Mechanism of chlorination of methane
Stage 3 termination
any step that stops chain-reaction by consuming
free-radicals
66
Halogenation of Alkanes
Higher alkanes
Chlorination of higher alkanes
can be used to prepare alkyl chlorides from
alkanes (frequently used as first step of
multi-step syntheses to introduce functional
group into alkanes, especially where all of the
hydrogens are equivalent)
420C
Examples
CH3CH3 Cl2
CH3CH2Cl HCl
67
Halogenation of Alkanes
Higher alkanes
Chlorination of higher alkanes
Major limitation - chlorination gives every
possible monochloride derived from
original carbon skeleton
- not much difference in reactivity of different
hydrogens in molecule
CH3CH2CH2CH2Cl
Example
Cl2
(28)
CH3CH2CH2CH3
h?
CH3CHCH2CH3
(72)
Cl
68
Halogenation of Alkanes
Higher alkanes
Chlorination of higher alkanes
- chlorination of butane gives a mixture of two
different monochlorides because butane contains
two different sets of hydrogens
- relative ratio (statistical product
distribution) of 2o to 1o monochlorobutanes
is calculated based on formula
rate of 2o H abstraction x of 2o Hs
2o

1o
rate of 1o H abstraction x of 1o Hs
69
Halogenation of Alkanes
Higher alkanes
Chlorination of higher alkanes
For chlorinations, the relative H abstraction
rates
3o H
2o H
1o H
type of H
rate of abstraction
5.2
3.9
1
Therefore, for butane
15.6
3.9 x 4
2o
72
2.6



6
1o
28
1 x 6
70
Halogenation of Alkanes
Higher alkanes
Chlorination of higher alkanes
Similarly, chlorination of isobutane gives a
mixture of isobutyl chloride and tert-butyl
chloride.
71
Halogenation of Alkanes
Higher alkanes
Chlorination of higher alkanes
72
Halogenation of Alkanes
Higher alkanes
Bromination of higher alkanes
For brominations, the relative H abstraction rates
3o H
2o H
1o H
type of H
rate of abstraction
1640
82
1
Br2
Therefore, for bromination of isobutane
hn
1640
1640 x 1
3o
99.5
182



1o
0.5
9 x 1
9
73
Halogenation of Alkanes
Higher alkanes
Bromination of higher alkanes
- bromination takes place practically by
substitution of only 3o hydrogens
- therefore, synthetically free-radical
bromination is more useful
Comparison of bromination and chlorination
chlorination gives a mixture of every possible
isomer having the same skeleton as the starting
alkane. Useful only when all hydrogens are
equivalent.
74
Halogenation of Alkanes
Comparison of bromination and chlorination
On the other hand, bromination is highly
selective toward substitution of tertiary
hydrogens. Major synthetic application is in
synthesis of tertiary alkyl bromides.
Br2
h?
Therefore, bromination is referred to as a highly
regioselective reaction for substitution of 3o
hydrogens.
Chlorination is non-regioselective.
75
End of Chapter 4