Chemistry 2213a Fall 2012 Western University
Topic 4. Haloalkanes (Alkyl Halides)
A. Structure and Nomenclature
Like hydrogen, the halogens have a valence of one. So, a halogen atom can
replace a hydrogen atom in a molecule, so the general formula of a saturated
mono-halo acyclic compound is C H n 2n+1X.
Therefore, treat X as an H when calculating unsaturation units. e.g. C 3 B4 =2
one unit of unsaturation.
Non-IUPAC, two-word names are commonly used for simple compounds. The
first word identifies the alkyl group, the second identifies the halogen.
IUPAC: 2-chlorobutane bromocyclohexane
Common: sec-butyl chloride cyclohexyl bromide Haloalkanes 2
The reactions that alkyl halides undergo strongly depend on the nature of the
alkyl position. It’s essential that we recognize the “type” of alkyl halide.
1. Primary halide (1°). The CH 2
carbon bearing the halogen
is bonded to one alkyl CH 3H B2 (CH 3 3CH B2
group and has two H.
2. Secondary halide (2°). The carbon
bearing the halogen is bonded to two
alkyl groups and one H.
3. Tertiary halide (3°). The carbon bearing CH
the halogen is bonded to three alkyl 3 Br
groups and no H. Cl
All the above have halogens bonded to sp carbon (alkyl). We need to know
that there can be aryl or vinyl halides, which have rather different chemistry
because the halogen is bonded to an sp carbon (covered later on). Haloalkanes 3
B. Physical Properties
The halogens are more electronegative than carbon, so an sp 3 + -
C–X bond is polar. The polar bond does not cause alkyl halides CH CH Br
to be water-soluble.
Halogenated organic compounds rarely occur in nature is why many organic
halides are highly toxic and are very slowly destroyed. However, we study alkyl
halides because they are very useful in laboratory syntheses. As well, they
serve as excellent examples of natural reaction mechanisms.
C. Characteristic Reactions
Haloalkanes can undergo substitution reactions, where a nucleophile replaces
the halogen (the leaving group). Haloalkanes 4
Nucleophiles can be either neutral or negatively charged, but they must have
at least one nonbonding pair of electrons. Leaving groups are all atoms/groups
that create a charge on an sp carbon atom before they leave.
The above reaction is a template for a wide range of reactions differing in Nu
and LG. If a neutrally charged nucleophile is used, there is usually a
deprotonation step after the substitution reaction. Haloalkanes 5
Because nucleophiles have nonbonding electrons, they can also act as bases.
Therefore, substitution and -elimination are frequently competing reactions.
D. Substitution Mechanisms
How does substitution occur? That is, how does the nucleophile replace the
leaving group? Two possibilities:
1.Nu waits until LG departs C on its own, after which Nu comes and takes
the empty spot; or
2.Nu kicks out the LG through backside attack. Haloalkanes 6
With mechanism #1, the rate of the reaction is dependent entirely on how fast
LG decides to leave on its own. This would entail first-order kinetics.
Rate = k [R−LG]
Whereas, the rate of mechanism #2 depends on how willing LG is to allow
itself to be kicked out, and also how good Nu is at kicking LG out. This entails
Rate = k [Nu] [R−LG]
S 2 Reaction Mechanism
This is a one-step mechanism that involves the collision of the reagents to form
a high-energy transition state that falls apart to give the products. Everything
happens at once (concerted). The nucleophile attacks as LG leaves. Haloalkanes 7
The stereochemical and energetic
requirements of the mechanism allow us
to predict various aspects.
Useful reactions have H sufficiently
exothermic so that products are formed
in good yield
1. The mechanism is bimolecular
Both the Nu and R−LG molecules must collide to form the transition state. This
is the only step of reaction, so it is the rate-determining step. The rate law is
Rate = k [Nu] [R−LG] Haloalkanes 8
2. Stereochemical inversion at the centre
Due to backside attack, the stereochemical configuration at that carbon is
Almost always, an R configuration becomes S, or an S becomes R. However,
the label sometimes remains the same even though inversion has occurred.
H COH C CH OCH
3 2 S N 2 3
Br NC Br
NC H H
The reason for the retention of the S label in this example is due to the change
in group priorities. In this case, the LG and the Nu don’t have the same priority. Haloalkanes 9
3. Steric bulk around the centre slows the reaction
Nu needs to attack from the back. If something is in its way, the reaction will be
The reaction works best when groups on the carbon are small. Large groups
block the incoming Nu.
In general, the rate of an S N reaction for alkyl halides is:
tertiary < secondary < primary < methyl
In fact, tertiary alkyl halides DO NOT react by S 2 Nt all. Haloalkanes 10
In the example below, the only product formed is one where substitution has
occurred at the secondary carbon.
CH 3 CH 3
4. Better the nucleophile, faster reaction
Better nucleophiles are better at kicking
out the LG.
In general, less-electronegative atoms are
better nucleophiles. And, anions (which
are more attracted to the carbon atom of
the haloalkane) are better than neutral. Haloalkanes 11
5. Aprotic solvents increase the reaction rate
Aprotic (non-protic) solvents do not have an H atom with a charge; i.e. they
can’t form hydrogen bonds.
In aprotic solvents, nucleophiles are much more reactive due to the lack of
stabilization from the solvent. The more reactive the nucleophile, the better the
nucleophile, and the faster is the reaction.
Common aprotic solvents
Note that this doesn’t
mean that an S 2 Nill not
occur at all in protic
solvents. They just prefer
aprotic solvents. Protic
solvents include water,
alcohols, acids, etc. Haloalkanes 12
6. Better leaving group, faster reaction
Better leaving groups are
those that are more stable.
We use the same criteria
used to assess the relative
stabilities of conjugate bases.
S 1 Reaction Mechanism
"top" and "bottom" products
LG Nu Nu
The first, rate-determining step involves the ionization of the R−LG bond to
form a carbocation intermediate. i.e. LG must come off on its own. The second 2
step is attack by Nu (neutral or anion) on both sides of the carbocation (sp =
planar) to yield the products. Haloalkanes 13
The reaction coordinate diagram is
just like the addition of HX to alkenes.
An S 1Nreaction also involves a
The reaction coordinate diagram and
mechanism tell us a lot…
1. The first, RDS is unimolecular
The rate-determining step is the
departure of LG on its own.
Rate = k [R−LG]
2. Mixtures of stereoisomers are formed
If a new stereocentre is formed, there will be a mixture of stereoisomers.
Because the carbocation intermediate is sp (flat), the Nu can attack either
face of the carbocation. Haloalkanes 14
If we start with any one enantiomer, we will obtain a racemic mixture. In this
case, an optically active reagent will give a mixture that is optically inactive. For
O O O
S N Cl