There are several factors that influence whether nucleophilic

substitution or elimination reactions take place. Among them is the type of

halide of the haloalkanes. The nature of the halogen substituent on the alkyl
halide is usually not very significant if it is Cl, Br or I. In cases where both SN2
and E2 reactions compete, chlorides generally give more elimination than do
iodides, since the greater electronegativity of chlorine increases the acidity
of beta-hydrogens. Even though alkyl fluorides are relatively unreactive,
when reactions with basic nucleophiles are forced, elimination occurs due to
its high electronegativity. In short, it can be said that similar reactions occur
when alkyl chlorides or iodides are used, but the speed of the reactions and
the exact distribution of products will change.
In addition, the types of haloalkanes also play an important role.
Primary haloalkane (1) mainly tend to undergo rapid substitution reaction
whereas tertiary haloalkane (3) mainly undergo elimination reaction.
Meanwhile, secondary haloalkane (2) undergo both substitution and
elimination. Primary haloalkanes will usually undergo S N2 substitution in
preference to E2 reaction. However, the E2 elimination reaction is favored if
a strong bulky base is used with heating. Meanwhile, for secondary
haloalkanes, both substitution and elimination is favored when dissolved in
protic solvent. Tertiary haloalkane undergo mainly elimination because it has
larger cloud that makes the nucleophile difficult to attack the partial positive
carbon. Thus, substitution is not favored at tertiary haloalkane. These are
summarized in the table below.

Alkyl Group

Anionic
Nucleophiles
( Weak Bases: I,
Br, SCN, N3,
CH3CO2 , RS,
CN etc. )

Primary
RCH2
Rapid SN2
substitution.

Secondary
R2CH
SN2 substitution
and / or E2
elimination
(depending on the
basicity of the
nucleophile).
Bases weaker
than acetate
(pKa = 4.8) give
less elimination.

Tertiary
R3C
E2 elimination
will dominate
with most
nucleophiles
(even if they
are weak
bases). No SN2
substitution
due to steric
hindrance.

Allyl
H2C=CHCH2
Rapid SN2
substitution for 1
and 2-halides.
For 3-halides a
very slow SN2
substitution or, if
the nucleophile is
moderately basic,
E2 elimination.

Benzyl
C6H5CH2
Rapid SN2 substitution
for 1 and 2-halides. For
3-halides a very slow
SN2 substitution or, if the
nucleophile is
moderately basic, E2
elimination. .

Contributors
William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry

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Similar reactions occur when alkyl chlorides or iodides are used, but the speed of the reactions
and the exact distribution of products will change.
https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/alhalrx1.htm

One conclusion, relating the structure of the R-group to possible products, should be
immediately obvious. If R- has no beta-hydrogens an elimination reaction is not possible,
unless a structural rearrangement occurs first. The first four halides shown on the left below do
not give elimination reactions on treatment with base, because they have no -hydrogens. The
two halides on the right do not normally undergo such reactions because the potential
elimination products have highly strained double or triple bonds.
It is also worth noting that sp2 hybridized CX compounds, such as the three on the right, do not
normally undergo nucleophilic substitution reactions, unless other functional groups perturb the
double bond(s).

When several reaction variables may be changed, it is important to isolate the effects of each
during the course of study. In other words: only one variable should be changed at a time,
the others being held as constant as possible. For example, we can examine the effect of
changing the halogen substituent from Cl to Br to I, using ethyl as a common Rgroup, cyanide
anion as a common nucleophile, and ethanol as a common solvent. We would find a common
substitution product, C2H5CN, in all cases, but the speed or rate of the reaction would increase
in the order: Cl < Br < I. This reactivity order reflects both the strength of the CX bond, and the
stability of X() as a leaving group, and leads to the general conclusion that alkyl iodides are the
most reactive members of this functional class.

1. Nucleophilicity
Recall the definitions of electrophile and nucleophile:
Electrophile: An electron deficient atom, ion or molecule that has an affinity for
an electron pair, and will bond to a base or nucleophile.
Nucleophile: An atom, ion or molecule that has an electron pair that may be
donated in forming a covalent bond to an electrophile (or Lewis acid).
If we use a common alkyl halide, such as methyl bromide, and a common solvent,
ethanol, we can examine the rate at which various nucleophiles substitute the methyl
carbon. Nucleophilicity is thereby related to the relative rate of substitution reactions at
the halogen-bearing carbon atom of the reference alkyl halide. The most reactive

nucleophiles are said to be more nucleophilic than less reactive members of the group.
The nucleophilicities of some common Nu:() reactants vary as shown in the following
Nucleophilicity: CH3CO2() < Cl() < Br() < N3() < CH3O() < CN() SCN() < I() < CH3S()

The reactivity range encompassed by these reagents is over 5,000 fold, thiolate being
the most reactive. Note that by using methyl bromide as the reference substrate, the
complication of competing elimination reactions is avoided. The nucleophiles used in this
study were all anions, but this is not a necessary requirement for these substitution
reactions. Indeed reactions 6 & 7, presented at the beginning of this section, are
examples of neutral nucleophiles participating in substitution reactions. The cumulative
results of studies of this kind has led to useful empirical rules pertaining to
nucleophilicity:
(i) For a given element, negatively charged species are more nucleophilic (and
basic) than are equivalent neutral species.
(ii) For a given period of the periodic table, nucleophilicity (and basicity)
decreases on moving from left to right.
(iii) For a given group of the periodic table, nucleophilicity increases from top to
bottom (i.e. with increasing size), although there is a solvent dependence due to
hydrogen bonding. Basicity varies in the opposite manner.
Some of the most important information concerning nucleophilic substitution and
elimination reactions of alkyl halides has come from studies in which the structure of the
alkyl group has been varied. If we examine a series of alkyl bromide substitution
reactions with the strong nucleophile thiocyanide (SCN) in ethanol solvent, we find large
decreases in the rates of reaction as alkyl substitution of the alpha-carbon increases.
Methyl bromide reacts 20 to 30 times faster than simple 1-alkyl bromides, which in turn
react about 20 times faster than simple 2-alkyl bromides, and 3-alkyl bromides are
essentially unreactive or undergo elimination reactions. Furthermore, -alkyl substitution
also decreases the rate of substitution, as witnessed by the failure of neopentyl bromide,
(CH3)3CCH2-Br (a 1-bromide), to react.
Alkyl halides in which the alpha-carbon is a chiral center provide additional information
about these nucleophilic substitution reactions. Returning to the examples presented at
the beginning of this section, we find that reactions 2, 5 & 6 demonstrate an inversion of
configuration when the cyanide nucleophile replaces the bromine. Other investigations
have shown this to be generally true for reactions carried out in non-polar organic
solvents, the reaction of (S)-2-iodobutane with sodium azide in ethanol being just one
example ( in the following equation the alpha-carbon is maroon and the azide
nucleophile is blue). Inversion of configuration during nucleophilic substitution has also
been confirmed for chiral 1-halides of the type RCDH-X, where the chirality is due to
isotopic substitution.

(S)-CH3CHICH2CH3 + NaN3

> (R)-CH CHN CH CH + NaI

3

We can now piece together a plausible picture of how nucleophilic substitution reactions
of 1 and 2-alkyl halides take place. The nucleophile must approach the electrophilic
alpha-carbon atom from the side opposite the halogen. As a covalent bond begins to
form between the nucleophile and the carbon, the carbon halogen bond weakens and
stretches, the halogen atom eventually leaving as an anion. The diagram on the right
shows this process for an anionic nucleophile. We call this description
the SN2mechanism, where S stands for Substitution, N stands for Nucleophilic
and 2 stands for bimolecular (defined below). In the SN2 transition state the alpha-carbon
is hybridized sp2 with the partial bonds to the nucleophile and the halogen having largely
p-character. Both the nucleophile and the halogen bear a partial negative charge, the full
charge being transferred to the halogen in the products. The consequence of rear-side
bonding by the nucleophile is an inversion of configuration about the alpha-carbon.
Neutral nucleophiles react by a similar mechanism, but the charge distribution in the
transition state is very different.
This mechanistic model explains many aspects of the reaction. First, it accounts for the
fact that different nucleophilic reagents react at very different rates, even with the same
alkyl halide. Since the transition state has a partial bond from the alpha-carbon to the
nucleophile, variations in these bond strengths will clearly affect the activation energy,
E, of the reaction and therefore its rate. Second, the rear-side approach of the
nucleophile to the alpha-carbon will be subject to hindrance by neighboring alkyl
substituents, both on the alpha and the beta-carbons. The following models clearly show
this "steric hindrance" effect.
The two models displayed below start
as methyl bromide, on the left, and ethyl
bromide, on the right. These may be
replaced by isopropyl, tert-butyl,
neopentyl, and benzyl bromide models by
pressing the appropriate buttons. (note
that when first activated, this display may
require clicking twice on the selected
button.) In each picture the nucleophile is
designated by a large violet sphere,
located 3.75 Angstroms from the alpha-carbon atom (colored a dark gray), and located
exactly opposite to the bromine (colored red-brown). This represents a point on the
trajectory the nucleophile must follow if it is to bond to the back-side of the carbon atom,
displacing bromide anion from the front face. With the exception of methyl and benzyl,
the other alkyl groups present a steric hindrance to the back-side approach of the
nucleophile, which increases with substitution alpha and beta to the bromine. The
hydrogen (and carbon) atoms that hinder the nucleophile's approach are colored a light
red. The magnitude of this steric hindrance may be seen by moving the models about in

the usual way, and is clearly greatest for tert-butyl and neopentyl, the two compounds
that fail to give substitution reactions.

Steric Hindrance to Rear-side Approach in Nucleophilic Substitution

View Isopropyl Bromide

View tert-Butyl Bromide

View Neopentyl Bromide

View Benzyl Bromide

Return to Methyl Bromide

Return to Ethyl Bromide

The stereoselectivity of SN2 reactions is in large part due to a stereoelectronic

effect.
This important factor will be described by clicking here.

4. Molecularity
If a chemical reaction proceeds by more than one step or stage, its overall velocity or
rate is limited by the slowest step, the rate-determining step. This "bottleneck concept"
has analogies in everyday life. For example, if a crowd is leaving a theater through a
single exit door, the time it takes to empty the building is a function of the number of
people who can move through the door per second. Once a group gathers at the door,
the speed at which other people leave their seats and move along the aisles has no
influence on the overall exit rate. When we describe the mechanism of a chemical
reaction, it is important to identify the rate-determining step and to determine its
"molecularity". The molecularity of a reaction is defined as the number of molecules or
ions that participate in the rate determining step. A mechanism in which two reacting
species combine in the transition state of the rate-determining step is
called bimolecular. If a single species makes up the transition state, the reaction would
be called unimolecular. The relatively improbable case of three independent species
coming together in the transition state would be called termolecular.

5. Kinetics
One way of investigating the molecularity of a given reaction is to measure changes in
the rate at which products are formed or reactants are lost, as reactant concentrations
are varied in a systematic fashion. This sort of study is called kinetics, and the goal is to
write an equation that correlates the observed results. Such an equation is termed a
kinetic expression, and for a reaction of the type: A + B > C + D it takes the

form: Reaction Rate = k[A] n[B] m, where the rate constant k is a proportionality constant
that reflects the nature of the reaction, [A] is the concentration of reactant A, [B] is the
concentration of reactant B, and n & m are exponential numbers used to fit the rate
equation to the experimental data. Chemists refer to the sum n + m as the kinetic
order of a reaction. In a simple bimolecular reaction n & m would both be 1, and the
reaction would be termed second order, supporting a mechanism in which a molecule of
reactant A and one of B are incorporated in the transition state of the rate-determining
step. A bimolecular reaction in which two molecules of reactant A (and no B) are present
in the transition state would be expected to give a kinetic equation in which n=2 and m=0
(also second order). The kinetic expressions found for the reactions shown at the
beginning of this section are written in blue in the following equations. Each different
reaction has its own distinct rate constant, k#. All the reactions save 7 display second
order kinetics, reaction 7 is first order.

It should be recognized and remembered that the molecularity of a reaction is a

theoretical term referring to a specific mechanism. On the other hand, the kinetic order of
a reaction is an experimentally derived number. In ideal situations these two should be
the same, and in most of the above reactions this is so. Reaction 7 above is clearly
different from the other cases reported here. It not only shows first order kinetics (only
the alkyl halide concentration influences the rate), but the chiral 3-alkyl bromide
reactant undergoes substitution by the modest nucleophile water with extensive
racemization. Note that the acetonitrile cosolvent does not function as a nucleophile. It
serves only to provide a homogeneous solution, since the alkyl halide is relatively
insoluble in pure water.
One of the challenges faced by early workers in this field was to explain these and other
differences in a rational manner.
Two discrete mechanisms for nucleophilic substitution reactions will be described in the
next section.

Nucleophilic Substitution Mechanisms

This page is the property of William Reusch. Comments, questions and errors should
be sent to whreusch@msu.edu.
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education. 05/05/2013