Download Preparation of Alkyl Halides

CH221 CLASS 18
CHAPTER 10: ALKYL HALIDES
Synopsis. This is an introductory class dealing with nomenclature, structure,
radical halogenation, allyl and benzyl radicals, formation and uses of some
organometallic compounds and oxidation/reduction.
Introduction
Halogenated organic compounds are widespread throughout nature and are very
important in industry and in the laboratory as synthetic intermediates. Some
examples of natural and commercially important organohalogen compounds are
given below, but see also p. 335 in the textbook for other examples from nature.
CH3Cl
Chloromethane (methyl chloride) - secreted by various organisms
from certain species of worms (acorn worm of Okinawa) to kelp, a variety of
seaweed
Cl
Epibatidine, from the South American frog,
Epipedobates tricolor. This compound is
a powerful pain killer
N
NH
H
CH2Cl2
dichloromethane
(methylene chloride)
ClCH=CCl2
Trichloroethylene
CH3-CCl3
1,1,1-Trichloroethane
CH2=CHCl
vinyl chloride, an important monomer
all useful
solvents
E.tricolor
The major types of organohalogen compounds are illustrated below, where it can
be seen that the classification depends on the type of carbon atom to which the
halogen is attached. Furthermore, it will be shown that the group alkyl halides,
which are especially emphasized in this course, can be subdivided into primary,
secondary and tertiary halides.
CH3
CH3CH2Br
an alkyl halide
Br
CH2=CHCl
a vinyl halide
an aryl halide
CH2Br
CH2=CHCH2Br
an allyl halide
special kinds of
alkyl halides
a benzyl halide
Naming Alkyl Halides
To name alkyl halides, carry out the following steps.
1. Find the longest chain and name it as the parent (if a double or triple bond is present,
it must be included in this chain).
2. Number the carbon atoms of the parent chain beginning at the end nearer the first
substituent, irrespective of whether it is alkyl or halogen.
E.g.
CH3
CH3
CH3CHCH2CHCHCH2CH3
The longest carbon chain has 7 carbons
= heptane
Br
CH3
Number from the left (first substituent at 2) gives
5-bromo-2,4-dimethylheptane
CH3
5 6 7
CH3CHCH2CHCHCH2CH3
1 2 3 4
Br
Note the following special situations.
(a) If more than one of the same halogen is present, name as follows.
Cl Cl
4 5 6
CH3CHCHCHCH2CH3
1 2 3
2,3-dichloro-4-methylhexane
CH3
(b) If different halogens are present, list them in alphabetical order:
Br
4 5
ClCH2CH2CHCHCH3
1 2 3
3-bromo-1-chloro-4-methylpentane
CH3
(c) If the parent can be properly numbered from either end, begin at the end nearer
the substutuent that has alphabetical precedence.
CH3
Br
CH3CHCH2CH2CHCH3
6 5 4 3 2 1
2-bromo-5-methylhexane
(NOT 5-bromo-2-methylhexane)
(d) For simple (linear) unsaturated halogen compounds, the halogen-containing carbon
atom is given the lower number.
E.g.
CH2
CHCH2Br
1-bromo-2-propene
Otherwise the numbering is devised to give the lowest total.
E.g.
Br
CH2
Cl
2-bromo-1-propene
CH3
CHCH3
1-methyl-2-chloro-4-bromocyclohexane
Br
Note that many halogen compounds are better known by their trivial names,
including methyl bromide (bromomethane), methylene chloride
(dichloromethane), allyl chloride (1-chloro-2-propene) and benzyl bromide
(bromophenylmethane).
Structure of Alkyl Halides: Polarity and Strength of the C-Hal (C-X) Bond
From Table 10.1 on p. 319 of the textbook, it is possible to make the following
generalizations for the halomethanes, CH3-X.
CH3F
CH3Cl
CH3Br
CH3I
C-X bond strength increases
C-X bond length increases
C-X bond polarity increases
Polarizability of X increases
The same generalizations are true for all alkyl halides. These factors make the
halogen-containing carbon atom electrophilic in nature, which in turn is
responsible for much of the important chemistry of alkyl halides (SN and E
reactions – Chapter 11, see class 19).
Preparation of Alkyl Halides
We have seen already that alkyl halides can be prepared by the halogenation or
hydrohalogenation of alkynes and alkenes (see classes 12, 13 and 15). We have
also seen that light-initiated radical halogenation of alkanes and cycloalkanes
yields alkyl halides (class 9). It is now time to time to consider the last method in
a bit more detail, noting particularly the range of reactivities and the synthetic
limitations of the method.
Radical Halogenation of Alkanes using Elemental Halogens: Chlorination
The one big limitation of this method (especially chlorination) is that it almost
inevitably leads to a (often complex) mixture of products. Even chlorination of
methane gives a mixture:
light
CH4
+
Cl2
CH3Cl, CH2Cl2, CHCl3 and CCl4
The situation is even worse for the chlorination of alkanes that have more than
one kinds of hydrogen:
light (h)
CH3CH2CH2CH3
+
Cl2
CH3CH2CH2CH2Cl
30%
CH3CH2CHCH3
Butane
1-chlorobutane
2-chlorobutane
70%
+ other (polychlorinated) products
CH3
CH3CCH3 35%
CH3
light (h)
+
CH3CHCH3
Cl2
2-chloro-2-methylpropane
Cl
CH3
Methylpropane
CH3CHCH2 Cl 65% 1-chloro-2-methylpropane
+ other (polychlorinated) products
In the first example, 30% of primary halide means that each one of the six
primary hydrogens (CH3) is responsible for 30%/6 = 5% of product, whereas 70%
of secondary alkyl halide means that each one of the four secondary hydrogens
(CH2) is responsible for 70%/4 = 17.5% of the product. Hence, chlorination at
secondary carbon occurs about 3.5 times the rate of chlorination at primary
carbon.
Similarly, in the second example, chlorination occurs at the single tertiary carbon
(CH) at about 5 times the rate of chlorination at the primary carbons.
The order of reactivity toward radical chlorination is
rel. rate
R-CH3
1o
1
<
R2CH2 <
2o
3.5
R3CH
3o
5
This order reflects the relative order of the C-H bond strengths: 3o < 2o < 1o.
Since less energy is needed to break a tertiary C-H bond than either a 2o or a 1o
C-H bond, the resulting tertiary radical is more stable than either a secondary or
primary radical, as we have already noted (see class 10).
However, although the rates of chlorination at different carbon atoms are
different, the difference is not great, so that in practice, some chlorination occurs
at all sites.
Radical chlorination has poor selectivity
Bromination, on the other hand, is much more selective, mainly because of the
lesser reactivity of the halogen species (in particular Br.):
CH3
Br2
CH3CHCH3
CH3
CH3
CH3CCH3
h
and
CH3CHCH2Br
Br
>99%
<1%
Bromination at Allylic and Benzylic Carbon Atoms
Compounds with allylic and benzylic hydrogen atoms can be brominated readily
using the mild brominating agent N-bromosuccinimide (NBS):
O
Br
NBr
(NBS)
O
allylic
initiator
O
+
O
benzylic
CH3
NBr
CH2Br
O
initiator
The reaction is thought to proceed via the following type of radical chain
mechanism:
NH
O
O
O
initiator
N
Br
N
.
+
Br
.
e.g. light
O
O
H
H
.
H
+
Br
.
+
HBr
an allyl radical
O
N
O
Br
+
N
HBr
O
H
+
Br2
O
H
.
H
+
Br
Br2
+
.
Br
etc
Bromination occurs preferentially at the allylic carbon because the allyl radical is
more stable than any other possibility (vinylic and alkyl), a fact that is reflected by
the relative bond energies:
allylic 360 kJ/mol
alkyl
400 kJ/mol H
H
H vinylic 445 kJ/mol
Thus, it is possible to extend the previous radical stability sequence:
Vinyl < 1o alkyl (CH3) < 2o alkyl (CH2) < 3o alkyl (CH) < allyl (benzyl)
Resonance Stabilization of Allyl and Benzyl Radicals
The enhanced stability of allyl and benzyl radicals is best explained by the
influence of resonance or delocalization.
One important synthetic consequence of the delocalized allyl radical is that more
than one bromination product is often obtained:
NBS
initiator
C5H11CH2CH
CH2
.
C5H11CH
CH
CH2
1-octene
C5H11CH
.
CH
CH2
Br2 thermodynamic
control
Br
C5H11CH CH
17%
CH2
3-bromo-1-octene
C5H11CH
CH
CH2
83%
1-bromo-2-octene
Preparing Alkyl Halides from Alcohols
Just as alkyl halides are often key synthetic intermediates, so are alcohols and
carbonyl compounds and hence a useful sequence is
>C=O
reduction
>CHOH
oxidation
>CHX
Br
Alkyl halides can be formed from alcohols by three basic methods, as
summarized below.
C
PBr3
Br
best for
3o alcohols
HX
C
OH
C
diethyl
ether
X X = I, Br, Cl
diethyl
ether
SOCl2,
pyridine
good for 1o and 2o
alcohols
C
Cl
E.g.
Cl
OH
SOCl2
CH3CH2CHCH3
CH3CH2CHCH3
pyridine
2-chlorobutane
Br
1/3 PBr
3
2-butanol
ether
35oC
CH3CH2CHCH3
2-bromobutane
Reactions of Alkyl Halides: Formation of Grignard Reagents and Other
Organometallic Compounds
Victor Grignard discovered that a dry alkyl halide will react with dry magnesium
metal in a dry ether solvent to produce an organometallic compound with that
behaves as if it has the structure R-Mg-X It is now called an alkylmagnesium
halide or Grignard reagent:
ether
R
X
+
Mg
R
Mg
X
dry
R = alkyl (all types) or
vinyl or alkynyl or
aryl
X = I, Br, Cl
In common with other organometallic compounds the metal-bound carbon atom
is highly nucleophilic,

CH3

Mg
I
methylmagnesium iodide
This carbon atom is also highly basic and hence Grignard reagents must be
prepared in the absence of both water and acidic groups such as –COOH, -OH
or –NH2 in the molecule.
Organometallic Coupling Reactions
Other organometallic compounds, like alkyllithiums, can be made in a similar
manner to Grignard reagents, although many of these are even more sensitive to
the presence of water.
2Li
nC4H9BLi
+
LiBr
nC4H9Br
pentane
n-butyllithium
dry!
These organolithium compounds can be used to make lithium diorganocopper
compound (LiR2Cu), known as Gilman reagents,
2 CH3Li
+
methyllithium
CuI
ether
- +
(CH3)2Cu Li
+
LiI
dry!
lithium dimethylcopper
Gilman reagents are useful coupling agents – they undergo alkylation reactions
with alkyl halides:
dry ether
+
nC9H19CH2I
nC9H19CH2CH3 + LiI + CH3Cu
(CH3)2Cu Li
iododecane
0oC
undecane
These are versatile reactions, occurring at vinyl and aryl carbon atoms, as well
as alkyl carbons,
nC7H15
H
nC7H15
H
+
(n-C
H
)
Cu
Li
C C
C C
4 92
C4H9-n
H
I
H
+ n-C4H9Cu + LiI
A Note on Oxidation and Reduction in Organic Chemistry
Oxidations and reductions (redox reactions) have been met already at several
points on this course (e.g. the perhydroxylation and hydrogenation of alkenes in
class 14 and the hydrogenation of alkynes in class 15). At this point, it is worth
noting qualitative ways (i.e. those that don’t involve the determination of oxidation
numbers) of describing organic oxidation/reduction reactions.
OXIDATION – a reaction that results in loss of electron density at
carbon, by either C-O, C-N or C-X (X = halogen) bond formation
or by C-H bond breaking
REDUCTION – a reaction that results in gain of electron density
at carbon, by either C-H bond formation or by C-O, C-N or C-X
bond breaking
Examples
A list of common compounds (and corresponding functional groups) is given
below, with alkanes being the most reduced and CO2, CCl4 being the most
oxidized. Any conversion left  right is an oxidation, whereas any conversion
right  left is a reduction.
CH3CH3
alkanes
CH2=CH2
alkenes
CH3OH
alcohols
CH3Cl
Alkyl halides
CH3NH2
amines
LOWEST
OXIDATION
LEVEL
CHCH
alkynes
CH2=O
aldehydes
and ketones
CH2Cl2
dihalogen
compounds
CH2=NH
imines
HCOOH
carboxylic
acids
CHCl3
trihalogen
compounds
HCN
nitriles
CO2
CCl4
HIGHEST
OXIDATION
LEVELS