Now that weve gone through the mechanisms of the E1 and E2 reactions, lets

take a moment to look at them side by side and compare them.

Heres how each of them work:

Heres what each of these two reactions has in common:

in both cases, we form a new C-C bond, and break a C-H bond and a

C(leaving group) bond

in both reactions, a species acts as a base to remove a proton, forming

the new bond

both reactions follow Zaitsevs rule (where possible)
both reactions are favored by heat.

Now, lets also look at how these two mechanisms are different. Lets look at this
handy dandy chart:

The rate of the E1 reaction depends only on the substrate, since the rate
limiting step is theformation of a carbocation. Hence, the more stable that
carbocation is, the faster the reaction will be. Forming the carbocation is the slow
step; a strong base is not required to form the alkene, since there is no leaving
group that will need to be displaced (more on that in a second). Finally there is no
requirement for the stereochemistry of the starting material; the hydrogen can be
at any orientation to the leaving group in the starting material [although well see
in a sec that we do require that the C-H bond be able to rotate so that its in the
same plane as the empty p orbital on the carbocation when the new bond is
formed].
The rate of the E2 reaction depends on both substrate and base, since the ratedetermining step is bimolecular (concerted). A strong base is generally
required, one that will allow for displacement of a polar leaving group. The
stereochemistry of the hydrogen to be removedmust be anti to that of the
leaving group; the pair of electrons from the breaking C-H bond donate into the
antibonding orbital of the C-(leaving group) bond, leading to its loss as a leaving
group.
Now were in a position to answer a puzzle that came up when we first looked at
elimination reactions. Remember this reaction where one elimination gave the
Zaitsev product, whereas the other one did not. Can you see why now?

So whats going on here?

The first case is an E2 reaction. The leaving group must be anti to the
hydrogen that is removed.

The second case is an E1 reaction.

In our cyclohexane ring here, the hydrogen has to be axial. Thats the only

way we can form a bond between these two carbons; we need the p orbital
of the carbocation to line up with the pair of electrons from the C-H bond that
were breaking in the deprotonation step. We can always do a ring flip to
make this H axial, so we can form the Zaitsev product.
Heres that deprotonation step:

As you can see, cyclohexane rings can cause some interesting complications
with elimination reactions! In the next post well take a detour and talk specifically
about E2 reactions in cyclohexane rings.

Having gone through the E1 mechanism for elimination reactions, weve

accounted for one way in which elimination reactions can occur. However, theres
still another set of data that describes some elimination reactions that we havent
adequately explained yet.
Heres an example of the reaction Im talking about:

Whats interesting about this reaction is that it doesnt follow the same rules that
we saw for the E1 reaction. Well talk about two key differences here.
Clue #1 The Rate Law
Remember that the E1 reaction has a unimolecular rate determining step (that
is, the rateonly depends on the concentration of the substrate?)
Well, when we look at the rate law for this reaction, we find that it depends on two
factors. Its dependent on the concentration of both substrate and the base.
That means that whatever mechanism we propose for this reaction has to explain
this data.

By the way, see how useful chemical kinetics can be? Theyre such simple
experiments measure reaction rate versus concentration and you get these
nice graphs out of it. I cant even begin to stress how important this data can be
in understanding reaction mechanisms. So simple, so elegant, and so useful.
Another note you might notice that the base here (CH3O-) is a stronger base
than we see for the E1 reaction (more on that later).
Second Clue: Stereochemistry
Heres the second key piece of information and we didnt talk about this for the
E1. The reaction below is very dependent on the stereochemistry of the
starting material.
When we treat this alkyl halide with the strong base, CH 3ONa, look at this
interesting result. Whats weird about this? Well, this seems to fly in the face
of Zaitsevs rule, right? Why dont we get the tetrasubstituted alkene here?

The mystery gets a little deeper. If, instead of starting with the alkyl halide above,
we label it with deuterium that is, we replace one of the hydrogens with its
heavy-isotope cousin that has essentially identical chemical properties we see
this interesting pattern:

Note how the group that is on the opposite face of the cyclohexane ring to the
leaving group (Br) is always broken.
In fact, if we use the molecule above and make just one modification, now we
actually do get the Zaitsev product!

See whats going

on? The hydrogen that is broken is always opposite, or anti to the leaving group.
So how do we explain these two factors?
Heres a hypothesis for how this elimination reaction works. It accounts for all the
bonds that form and break, as well as the rate law, and crucially the
stereochemistry.

In this mechanism, the base removes the proton from the alkyl halide that is
oriented anti to the leaving group, and the leaving group leaves all in one
concerted step.
Since its an elimination reaction, and the rate law is bimolecular, we call this
mechanism theE2.

In the next post, well directly compare the E1 and E2 reactions

Last time in this walkthrough on elimination reactions, we talked about two types
of elimination reactions. In this post, were going to dig a little bit deeper on one
type of elimination reaction, and based on what experiments tell us, come up with
a hypothesis for how it works.
Heres the reaction. First, look at the bonds that are being formed and broken.
This is a classic elimination reaction were forming a new CC() bond, and
breaking a CH and Cleaving group (Br here) bond.

But now we want to know more than just what happens. We want to
understand how it happens. Whats the sequence of bond-forming and bond
breaking? To understand HOW it happens, we need to look at what the data tells
us. Thats because chemistry is an empirical science; we look at the evidence,
and then work backwards.
First Clue The Rate Laws
Lets look at the first important clue for this reaction. We can measure reaction
rates quite readily. When we vary the concentration of the substrate, the reaction
rate increases accordingly. In other words, there is a first-order dependence of
rate on the concentration of substrate.
However, if we vary the concentration of the base (here, H 2O) the rate of the
reaction doesnt change at all.

What information can we deduce from this? The rate determining step for this
reaction (whatever it is) therefore does not involve the base. Whatever
mechanism we draw will have to account for this fact.
Second Clue Dependence of Rate on Substrate
Another interesting line of evidence we can obtain from this reaction is through
varying the type of substrate, and measure the rate constant that results. So if
we take the simple alkyl halide on the far left (below) where the carbon attached
to Br is also attached to 3 carbons (this is called a tertiary alkyl halide), the rate
is faster than for the middle alkyl halide (a secondary alkyl halide) which is itself
faster than a primary alkyl halide (attached to only one carbon in addition to Br).
So the rate proceeds in the order tertiary (fastest) > secondary >> primary
(slowest)

Any mechanism we draw for this reaction would likewise have to account for this
fact. What could be going on such that tertiary substrates are faster than
primary?
Third Clue This Elimination Reaction Competes with the SN1 Reaction
A final interesting clue about the mechanism of this reaction concerns the byproducts that are often obtained. For instance, when the alkyl halide below is
subjected to these reaction conditions, we do obtain the expected elimination
product. However, we also get substitution reactions in the product mix as well.
Remember substitution reactions involve breakage of C-(leaving group) and
formation of C-(nucleophile). What makes this particular starting alkyl halide
particularly interesting is that the carbon attached to Br is a stereocenter. And if
we start with a single enantiomer of starting material here, we note that the
substitution product formed is a mixture of stereoisomers. Note that both
inversion and retention of stereochemistry at the stereocenter has occurred.
Weve seen this pattern before its an S N1 reaction!

This last part is a very important clue. If an SN1 reaction is occurring in the
reaction mixture, looking back at the mechanism of the SN1 could help us think

about what type of mechanism might be going on in this case to give us the
elimination product.
Taking all of these clues into account, whats the best way to explain what
happens? This:

The reaction is proposed to occur in two steps: first, the leaving group
leaves, forming a carbocation. Second, base removes a proton, forming the
alkene. This nicely fits in with the three clues mentioned above. [Also note that
the more substituted alkene is formed here, following Zaitsevs rule].
Similar to the SN1 mechanism, this is referred to as the E1
mechanism (elimination, unimolecular).

So whats going on in the other type of elimination reaction? Thats the topic for
the next post

3. The E1 Reaction
Just as there were two mechanisms for nucleophilic substitution, there are two
elimination mechanisms. The E1 mechanism is nearly identical to the SN1
mechanism, differing only in the course of reaction taken by the carbocation
intermediate. As shown by the following equations, a carbocation bearing betahydrogens may function either as a Lewis acid (electrophile), as it does in the SN1
reaction, or a Brnsted acid, as in the E1 reaction.

Thus, hydrolysis of tert-butyl chloride in a mixed solvent of water and acetonitrile

gives a mixture of 2-methyl-2-propanol (60%) and 2-methylpropene (40%) at a rate
independent of the water concentration. The alcohol is the product of an SN1 reaction
and the alkene is the product of the E1 reaction. The characteristics of these two
reaction mechanisms are similar, as expected. They both show first order kinetics;
neither is much influenced by a change in the nucleophile/base; and both are
relatively non-stereospecific.
(CH3)3CCl + H2O

> [ (CH ) C(+) ] + Cl + H O > (CH ) COH +

3 3

()

3 3

(CH3)2C=CH2 + HCl + H2O

To summarize, when carbocation intermediates are formed one can expect them to
react further by one or more of the following modes:
1. The cation may bond to a nucleophile to give a substitution product.
2. The cation may transfer a beta-proton to a base, giving an alkene product.
3. The cation may rearrange to a more stable carbocation, and then react by
mode #1 or #2.

Since the SN1 and E1 reactions proceed via the same carbocation intermediate, the
product ratios are difficult to control and both substitution and elimination usually take
place.
Having discussed the many factors that influence nucleophilic substitution and
elimination reactions of alkyl halides, we must now consider the practical problem of
predicting the most likely outcome when a given alkyl halide is reacted with a given
nucleophile. As we noted earlier, several variables must be considered, the most
important being the structure of the alkyl group and the nature of the
nucleophilic reactant. 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.
Indeed, although alkyl fluorides are relatively unreactive, when reactions with basic
nucleophiles are forced, elimination occurs (note the high electronegativity of
fluorine).

1. The E2 Reaction
We have not yet considered the factors that influence elimination reactions, such as
example 3 in the group presented at the beginning of this section.
(3) (CH3)3C-Br + CN() > (CH3)2C=CH2 + Br() + HCN
We know that t-butyl bromide is not expected to react by an SN2 mechanism.
Furthermore, the ethanol solvent is not sufficiently polar to facilitate an SN1 reaction.
The other reactant, cyanide anion, is a good nucleophile; and it is also a decent
base, being about ten times weaker than bicarbonate. Consequently, a base-induced
elimination seems to be the only plausible reaction remaining for this combination of
reactants. To get a clearer picture of the interplay of these factors consider the
reaction of a 2-alkyl halide, isopropyl bromide, with two different nucleophiles.

In the methanol solvent used here, methanethiolate has greater nucleophilicity than
methoxide by a factor of 100. Methoxide, on the other hand is roughly 106 times more
basic than methanethiolate. As a result, we see a clear-cut difference in the reaction
products, which reflects nucleophilicity (bonding to an electrophilic carbon)
versus basicity (bonding to a proton). Kinetic studies of these reactions show that
they are both second order (first order in RBr and first order in Nu:()), suggesting a
bimolecular mechanism for each. The substitution reaction is clearly SN2. The
corresponding designation for the elimination reaction is E2. An energy diagram for
the single-step bimolecular E2 mechanism is shown on the right. We should be
aware that the E2 transition state is less well defined than is that of SN2 reactions.
More bonds are being broken and formed, with the possibility of a continuum of
states in which the extent of CH and CX bond-breaking and C=C bond-making
varies. For example, if the Rgroups on the beta-carbon enhance the acidity of that
hydrogen, then substantial breaking of CH may occur before the other bonds begin

to be affected. Similarly, groups that favor ionization of the halogen may generate a
transition state with substantial positive charge on the alpha-carbon and only a small
degree of CH breaking. For most simple alkyl halides, however, it is proper to
envision a balanced transition state, in which there has been an equal and
synchronous change in all the bonds. Such a model helps to explain an important
regioselectivity displayed by these elimination reactions.
If two or more structurally distinct groups of beta-hydrogens are present in a given
reactant, then several constitutionally isomeric alkenes may be formed by an E2
elimination. This
situation is illustrated
by the 2-bromobutane
and 2-bromo-2,3dimethylbutane
elimination examples
given below.

By using the strongly

basic hydroxide
nucleophile, we direct
these reactions
toward elimination. In
both cases there are
two different sets of
beta-hydrogens
available to the
elimination reaction
(these are colored red
and magenta and the alpha carbon is blue). If the rate of each possible elimination
was the same, we might expect the amounts of the isomeric elimination products to
reflect the number of hydrogens that could participate in that reaction. For example,
since there are three 1-hydrogens (red) and two 2-hydrogens (magenta) on betacarbons in 2-bromobutane, statistics would suggest a 3:2 ratio of 1-butene and 2butene in the products. This is not observed, and the latter predominates by 4:1. This
departure from statistical expectation is even more pronounced in the second
example, where there are six 1-beta-hydrogens compared with one 3-hydrogen.
These results point to a strong regioselectivity favoring the more highly substituted
product double bond, an empirical statement generally called the Zaitsev Rule.
The main factor contributing to Zaitsev Rule behavior is the stability of the alkene.
We noted earlier that carbon-carbon double bonds are stabilized (thermodynamically)
by alkyl substituents, and that this stabilization could be evaluated by
appropriate heat of hydrogenation measurements. Since the E2 transition state has
significant carbon-carbon double bond character, alkene stability differences will be
reflected in the transition states of elimination reactions, and therefore in the
activation energy of the rate-determining steps. From this consideration we anticipate
that if two or more alkenes may be generated by an E2 elimination, the more stable
alkene will be formed more rapidly and will therefore be the predominant product.

This is illustrated for 2-bromobutane by the energy diagram on the right. The
propensity of E2 eliminations to give the more stable alkene product also influences
the distribution of product stereoisomers. In the elimination of 2-bromobutane, for
example, we find that trans-2-butene is produced in a 6:1 ratio with its cis-isomer.
The Zaitsev Rule is a good predictor for simple elimination reactions of alkyl
chlorides, bromides and iodides as long as relatively small strong bases are used.
Thus hydroxide, methoxide and ethoxide bases give comparable results. Bulky bases
such as tert-butoxide tend to give higher yields of the less substituted double bond
isomers, a characteristic that has been attributed to steric hindrance. In the case of 2bromo-2,3-dimethylbutane, described above, tert-butoxide gave a 4:1 ratio of 2,3dimethyl-1-butene to 2,3-dimethyl-2-butene ( essentially the opposite result to that
obtained with hydroxide or methoxide). This point will be discussed further once we
know more about the the
structure of the E2
transition state.

Bredt's Rule
The importance of
maintaining a
planar configuration
of the trigonal
double-bond
carbon components
must never be
overlooked. For
optimum pi-bonding
to occur, the porbitals on these
carbons must be parallel, and the resulting doubly-bonded planar
configuration is more stable than a twisted alternative by over 60 kcal/mole.
This structural constraint is responsible for the existence of alkene
stereoisomers when substitution patterns permit. It also prohibits certain
elimination reactions of bicyclic alkyl halides, that might be favorable in
simpler cases. For example, the bicyclooctyl 3-chloride shown below
appears to be similar to tert-butyl chloride, but it does not undergo elimination,
even when treated with a strong base (e.g. KOH or KOC4H9). There are six
equivalent beta-hydrogens that might be attacked by base (two of these are
colored blue as a reference), so an E2 reaction seems plausible. The problem
with this elimination is that the resulting double bond would be constrained in
a severely twisted (non-planar) configuration by the bridged structure of the
carbon skeleton. The carbon atoms of this twisted double-bond are colored
red and blue respectively, and a Newman projection looking down the twisted
bond is drawn on the right. Because a pi-bond cannot be formed, the
hypothetical alkene does not exist. Structural prohibitions such as this are
often encountered in small bridged ring systems, and are referred to
as Bredt's Rule.

Bredt's Rule should not be applied blindly to all bridged ring systems. If large
rings are present their conformational flexibility may permit good overlap of
the p-orbitals of a double bond at a bridgehead. This is similar to recognizing
that trans-cycloalkenes cannot be prepared if the ring is small (3 to 7membered), but can be isolated for larger ring systems. The anti-tumor agent
taxol has such a bridgehead double bond (colored red), as shown in the
following illustration. The bicyclo[3.3.1]octane ring system is the smallest in
which bridgehead double bonds have been observed. The drawing to the
right of taxol shows this system. The bridgehead double bond (red) has a cisorientation in the six-membered ring (colored blue), but a trans-orientation in
the larger eight-membered ring.

2. Stereochemistry of the E2 Reaction

E2 elimination reactions of certain isomeric cycloalkyl halides show unusual
rates and regioselectivity that are not explained by the principles thus far
discussed. For example, trans-2-methyl-1-chlorocyclohexane reacts with
alcoholic KOH at a much slower rate than does its cis-isomer. Furthermore,
the product from elimination of the trans-isomer is 3-methylcyclohexene (not
predicted by the Zaitsev rule), whereas the cis-isomer gives the predicted 1methylcyclohexene as the chief product. These differences are described by
the first two equations in the following diagram.
Unlike open chain structures, cyclic compounds generally restrict the spatial
orientation of ring substituents to relatively few arrangements. Consequently,
reactions conducted on such substrates often provide us with information
about the preferred orientation of reactant species in the transition state.
Stereoisomers are particularly suitable in this respect, so the results shown
here contain important information about the E2 transition state.

The most sensible interpretation of the elimination reactions of 2- and 4substituted halocyclohexanes is that this reaction prefers an anti
orientation of the halogen and the beta-hydrogen which is attacked by the
base. These anti orientations are colored in red in the above equations. The
compounds used here all have six-membered rings, so the anti orientation of
groups requires that they assume a diaxial conformation. The observed
differences in rate are the result of a steric preference for equatorial
orientation of large substituents, which reduces the effective concentration of
conformers having an axial halogen. In the case of the 1-bromo-4-tertbutylcyclohexane isomers, the tert-butyl group is so large that it will always
assume an equatorial orientation, leaving the bromine to be axial in the cisisomer and equatorial in the trans. Because of symmetry, the two axial betahydrogens in the cis-isomer react equally with base, resulting in rapid
elimination to the same alkene (actually a racemic mixture). This reflects the
fixed anti orientation of these hydrogens to the chlorine atom. To assume a
conformation having an axial bromine the trans-isomer must tolerate serious
crowding distortions. Such conformers are therefore present in extremely low
concentration, and the rate of elimination is very slow. Indeed, substitution by

hydroxide anion predominates.

A similar analysis of the 1-chloro-2-methylcyclohexane isomers explains both
the rate and regioselectivity differences. Both the chlorine and methyl groups
may assume an equatorial orientation in a chair conformation of the transisomer, as shown in the top equation. The axial chlorine needed for the E2
elimination is present only in the less stable alternative chair conformer, but
this structure has only one axial beta-hydrogen (colored red), and the
resulting elimination gives 3-methylcyclohexene. In the cis-isomer the smaller
chlorine atom assumes an axial position in the more stable chair
conformation, and here there are two axial beta hydrogens. The more stable
1-methylcyclohexene is therefore the predominant product, and the overall
rate of elimination is relatively fast.
An orbital drawing of the anti-transition state is shown on the right. Note that
the base attacks the alkyl halide from the side opposite the halogen, just as in
the SN2 mechanism. In this drawing the and carbon atoms are undergoing
a rehybridization from sp3 to sp2 and the developing -bond is drawn as
dashed light blue lines. The symbol R represents an alkyl group or hydrogen.
Since both the base and the alkyl halide are present in this transition state,
the reaction is bimolecular and should exhibit second order kinetics. We
should note in passing that a syn-transition state would also provide good
orbital overlap for elimination, and in some cases where an anti-orientation is
prohibited by structural constraints syn-elimination has been observed.
It is also worth noting that anti-transition states were preferred in
several addition reactions to alkenes, so there is
an intriguing symmetry to these inverse structural
transformations.