SN Mechanism

Download as pdf or txt
Download as pdf or txt
You are on page 1of 8

330 ADVANCED ORGANIC CHEMISTRY

these substrates, though for different reasons (Seciion 4.2). SNI reactions Dr

carbocations which must be


planar. rigid cage ike structures of the
Becauseof substrates ihronvph
carbon atoms cannot assume planarity, hence, heterolysis leading to the formation of
ol
also prevented Consequently, bridgehcad carbons are resistant towards substitution
ation brby ndyehea
carbocal ion
mechanism. For example, 1-chloroapocamphane docs not react refluxing with 30% KeS
on

ethanol for 21I hours, although analogous open-chain systems react readily. However,ifh r
ver, if the
large enough, SNI reactions should be possible, because nearly planar carbocation may
be
rings ate
there. For example. [2. 2. 2 ]bicyclic systems undergo SNI reactions much faster than sm pee
systems, though the reaction is still slower than with analogous open-chain systems
following rates were observed for solvolysis in 80% aqueous ethanol at 25°C: Thus. the
Br

Br Br
Open chain system 2.2.2]bicyclic system [2,2, 1Jbicyclic system
(-butyl bromide) ((-bromobicyclo[2, 2, 2]octane) (1-bromo-7, 7-dimethyl
bicyclo[2, 2, 1] heptane)
Rate: 10 1014

4.2 SN2 MECHANISM


Let us take the example of alkaline hydrolysis of methyl bromide to give methanol.
e
CH,Br +0H CH,OH+Br
(Direct displacement)
This is an SN2 (direct displacement). reaction and proceeds through the SN2 mechanin
discussed below:
SN2 mechanism is a one-step (concerted) process and involves no intermediate. In this
reaction
the nucleophile attacks the substrate from the just opposite (back) side (at 180°) to the
The C-OH bond is formed as the C-Br bond is broken:
leaving grouD.

H .HH
H
HO+ HC-Br HO---Br HO-C-H + Br
H H
L H
Transition state Substitution product
The energy necessary to break the C-Br bond is
supplied by simultaneous
C-OH bond. In the transition state (TS) the nucleophile and the leaving
formation of the
group are both 50% bonded
to the carbon being attacked. The three
nonreacting groups and the central carbon atom are
appoximately coplanar in the TS, i.e., the central carbon atom has gone froni its initial
hybridisation to an sp state with an approximately perpendicular p orbital. One lobe of this p orbit
overlaps with the nucleophile, and the other with the leaving group.
Evidence for the SN2 mechanism
1. Kinetics: The SN2 reaction is a second-order reaction following the rate-law given below.

Rate k
=

substrate][nucleophile
PHILIC SUBSTITUTION
ALIPHA 331

That is, the


the rate otf the SN2 reaction
rate
depends on both the concentration of the
acking nucleophile. This rate law has been found to apply in many cases. Ifsubstrate
and tnat
of
t h ea t t a c k i
a large excess of
ent, e.g.
is present, e.g. in solvolysis, the mechanism may still be
nucleophile
ally determined kinetices will be first order bimolecular, although the
experimental

R =k |substrate]

SuCuch kinetics are called pseudo first order. Thus, the kinctic evidence does not necessarily lead
to
corect
conclusions in all the cases.
We have noted that the 2 in SN2 denotes bimolecular. It must be remembered that it is not
same as second order.
always the
As mentioned above in the case
of solvolysis, the molecularity is 2 but the
ander kinetics. The molecularity refers to the number of species (molecules, reaction shows
ions, etc.) that the
are
irst

undergoing bond--breaking and/or bond-formation in one step of the reaction, usually the
te-determining step. The molecularity is not an experimentally determined while the quantity, order
af a reaction is experimentally determined. The molecularity has significance only in the light of the
narticular mechanism chosen for the reaction and is susceptible to re-evaluation, in the light of
par
additional experimental information about the reaction in a way that the order cannot be.
2. Stereochemistry: The SN2 reaction proceeds with inversion of configuration at the carbon
at which the substitution has taken place. SN2 reaction is a stereospecife reaction. For example:
Me Me
EtO+Ph- -Cl EtO Ph +C1

H H
100% R 100% S

Thus, in the SN2 reaction an enantiomerically pure reactant leads to an enantiomerically pure
product with inversion of configuration. This is a very strong evidence for the SN2 mechanism
because it predicts inversion of configuration in view of the attack of the nucleophile from the
backside of the leaving group in a one-step process. This inversion of configuration is called Walden
inversion (1893) and was observed long before the SN2 mechanism was proposed by Hughes and
Ingold (1937).
3. Formation of a single substitution product: SN2 reactions usually yield single substitution
products. This is evidence that these are one-step reactions, i.e, they do not proceed via reactive
intermediates. This is ulike SNI reactions which are often accompanied by rearrangement, and
involve carbocation intermediate.
4. No substitution at bridgehead carbons: Ifthe SN2 mechanism is correct. the compounds
with potential leaving groups at bridgehead carbons should not be ableto react by this mechanism.
his is because the SN2 mechanism requires the backside attact by the nucleophile, inversion of
Coniguration, and coplanarity of the three nonreacting groups in the TS all of which are prevented at
tne bridgehead carbons due to rigid cage like structures of the compounds containing the bridgehead
carbons. For example, under SN2 conditions 1-bromo-3,3-dimethylbicyclo|2.2.2]octane is resistant
Owards reaction with ethoxide ion, whereas the open-chain analogues underwent the reactions
readily

EtO
No reaction
SN2 conditions
Br
ADVANCED ORGANIC CHEMISTRY
332
and
o ee"ope substitutim hy both the SNI
is inert
1-bromotripreene
Problem 1. Explain why planar
which has
SN2 mechanisms? ermeidate
reactions proceed througn c b c a
cage like
of ,1-bromotriptycene, the bridgehead
structure

Solution: SNI
ation at the bridgehead position doe
the following rigid f o r m a t i o n of a
carboca ti
structure. Because of
the SNI reactions.
carbon cannot assume planarity. hence, is inert to
1-bromotriptycence

hot take place. Conscquently.

Br
inversion of configuration and
nucleophile,
attack by the prevented at the bridgehead
du
reactions require the backside all of these are
SN2 the TS, substitution
groups in inert to nucleophilic by
coplananity of the three nonreacting Thus, it 1S
1-bromotriptycene.
of
cage like
structure
to the rigid
SN2 mechanism. on treatment with sodium iodida
a racemic product
(+)-4-Bromo-2-pentene forms
Problem 2.
stable allylic carbocation which is
Explain why? formation of relatively
Solution: This is due to the should be noted that there is no
no
a racemic product. It
from either side of its plane
give to
front-side.
attacked carbocation to shield its
the neighbourhood ofthe
leaving group (Br) in
CH3-CH= CH-CH-CH +
Br
CH-CH=CH- CH-CH3

Br
Nal CHa-CH=CH-CH-CH
-NaBr
I
Racemic product
and lIl without racemisation
Problem 3. Explain the formation of a mixture of optically pure ll
when epoxide I reacts with acidic methanol (for structures of 1-I see the solution).
Solution: Me
MeO R Et

Me
Et i C o MeOH,SN Me Et H
0-H
H,C CH,OH
() HO-CH2 Inversion of configuration
(III)
MeOH,SN2-H
Me
OH
Eti C

M e o - H

Retention of configuration
ALIPHATIC UCLEOPHILIC SUBSTITUTION 333
CN2 reaction occurs at the less hindered carbon of the protonated epoxide I without disturbing the
centre to give the product il with retention of configuration. SNI attack occurs on the 1-carbon of
chi ide to give III. The front-side of the involved carbocation is shielded by the leaving group
tn thus, the attack occurs from the backside resulting in inversion of
configuration.
(
Deoblem 4. Trans-2-chlorocyclohexanol gives epoxycyclohexane in high yield on treatment with a
ewhereas the cis ISomer does not react in this way. Explain why?
Solution: In the trans isomer nucleophilic - 0 replaces CI by a backside attack
atramolecular SN2)) to give epoxycyclohexane in high yield.

OH
Intramolecular
OH SN2

CI Cl
In the case of cis isomer, the nucleophilic-0 is not in a favourable position for the backside
attack. Here Cl and H are trans to each other and undergo elimination to give a vinyl alcohol which
tautomerises to a ketone.
H
OH O
HO
H OH
-HCI
Tautomerisation

The backside attack by nucleophile is an essential requirement of SN2 without which these
reactions are not possible.

4.3 NEIGHBOURING GROUP PARTICIPATION (NEIGHBOURING GROUP


MECHANISM)
A number of nucleophilic substitution reactions are known which occur with complete retention
(no inversion or racemisation) of configuration and with unexpectedly greater rate of reaction. In
these cases usually there is an atom or group with an unshared electron pair ß to the leaving group (or
sometimes farther away). The mechanism operating in such cases is called neighbouring group
mechanism or neighbouring group participation. It consists of two consecutive SN2 substitutions
with inversion of configuration, thus, the net result is retention of configuration. In the first step of
this reaction the neighbouring group acts as a nucleophile pushing out the leaving group. In the
second step the external nucleophile pushes out the neighbouring group. A common feature of all
neighbouring group mechanisms is the formation of a cyclic intermediate.
Step 1. Slow Intermolecular SN2
intramolecular SN2 Step 2. Fast
(inversion) (inversion)
C- -C-C
Nu
Nu
Netr esu s retention
of configuration

Since, the neighbouring group acting as the nucieophile (Z is present in the same molecule and
is immediately available for the attack. such reactions occur thousands times faster than comparable
R =0
C

MECHANISMS
4.5 MIxED SN1 AND SN2
conditions show al the
reactions under a given set of
Certain nucleophilic substituion mechanism, but there are certain
others seem to proceed by SNI
characteristics of SN2 mechanisms: between, a mechanistic
cannot be characterized so easily.
There s e e m s to be something in
which or SN2
cases
where it is not clear whether the reaction
is proceeding through SNI
borderline region
devised for explaining these borderline
cases:
mechanism. Two theories have been borderiine behaviour is
mechanisms : According to this theory
1. Simultaneous SN1 and SN2
mechanisms in the some vessel. i. e.
some
both the SNI and SN2
caused by simultaneous occurring of
the SN2 mechanism.
molecules react by SN1, while others react by
This theory is very broad and applies
2. The intermediate mechanism theory (Sneen, 1965) :
saturated carbon. All SN1
not only to borderline cases
but also to all nucleophilic substitutions at a
mechanism).
one basic mechanism (the ion pair
and SN2 reactions can be accommodated by only
ion pair which is then converted to products :
The substrate first ionises to an intermediate
k k
RX R x = products
The difference between SN1 and SN2 mechanisms
is that in the former case the formation of the
mechanism its destruction (k,) is rate-determining.
ion pair (k) is rate-determining, whereas in SN2
i.e, when k^ >kj, the mechanism is SNI,
and when k^ >k2, the mechanism is SN2. The borderline
behaviour is found when kj = k2.

4.6 THE SET MECHANISM


mechanism is highly probable. it has
In nucleophilic substitution reactions where SNI
some
involved. In such cases
been shown, by esr detection of the intermediate, that free radicals are actually
is an electron donor. The mechanism
a carbocation is a good electron acceptor and nucleophile
the reaction between the
involved is named as SET (single electron transfer) mechanisms, e.g,
triphenyimethyl cation and 7-butoxide ion
PhC+1-BuO > PhC+t-BuO >I-BuOCPh

4.7 FACTORS AFFECTINGREACTIVITY IN sN REACTIONS


Evidence for the SN1 mechanism
1. Kinetics : The SNI reaction is a first order reaction following the rate-law given below:
Rate = k [substrate]
That is, the rate of the SNI reaction depends only on the concentration of the substrate and it is
independent of the concentration and nucleophilicity of the attacking nucleophile. Thus, kinetics is a
very strong evidence for SNI mechanism.
2. Stereochemistry: The SNI reactions proceed with partial racemisation and some
inversion.
In SN1 reactions an intermediate carbocation is formed which is planar, and the nucleophile
should attack with equal facility from either side of the plane, resulting in complete racemisation.
However, in practice the expected complete racemisation is rarely observed. Usually, there is 5
20% inversion. This may be explained
by considering that the attack by a nucleophile
occurs before

the leaving group has completely departed from the neighbourhood of thecarbocation, thus, to a
certain extenttheleaving group shields the front-side ofthe carbocationfrom attack. Consequenily,
the backside attack is preferred to some extent resulting in the inversion of configuration.
The more stable the carbocation, the greater is the
proportion of racemisation. This is because 1n
suchcasestheleaving group gets time to leavetheneighbourhood of thecarbocationbeforethe atack
by a nucelphile occurs, thus,
there is almost equal facility for attack from
either side ot the
carbocation plane leading to a greater degree of racemisation. For example, the solvolysis of
ALIPHATIC NUCLEOPHILIC SUBSTITUTION 329

PhCHMeCI. which can form a stabilised benzylic carbocation, leads to 98% racemisation, while
(+)P
CHCHMeCI (2-octyl chloride). where no comparable stabilisation can occur, leadsto only 34%

a
cemisation.
racem Insolvolysisreactions,the morenucleophilicisthesolvent,the greateris the proportion
inversion. This is due to the fast attack of the more nucleophilic solvent molecule from the

acksidebut, not from the front-side which is shiclded by the leaving group. For example, the
ba
solvolysis of PHCHMeClin mixture of 80% acetone and 20% water leads to 98% racemisation
(see above). but in the more nucleophilic water alone to only 80%. i.e., the greater proportion of
inversion.

The role of lon pairs


The stereochemistry of SN1 reactions discussed above is easily understandable if the heterolysis
in its rate-determining step follows the following sequence

R-X
Rx R x R+X
III
Here I is an intimate, contact or tight ion pair, II a solvent separated ion pair, and l the
dissociated ions (each surrounded by solvent molecules). In I and II, X is called the counterion. The
reaction in which the intimate ion pair recombines to give the original substrate is referred to as
iniernal retur. The reaction product can be formed by the attack of nucleophile at any stage. The
intimate ion I is likely to lead to inversion, as the attack can take place from the backside, but not
from the front-side which is shielded by X. Attack in II is more likely from backside, leading to
racemisation, whereas attack on l can take place with equal facility from either side. Thus, as we
proceed from I to II the degree of racemisation increases, and proportion of inversion decreases. As
the stability of R increases and the power of attacking nucleophile decreases, the proportion of I
increases.
3 . Formation of rearranged products : Rearragement is one of the characteristic features of
carbocations. Because of strong corelation between rearangement and formation of carbocations,
rearrangement is often taken as an indication of an SNI mechanism, which are frequently
accompanied by rearrangement. For example
CI

MeCHCH=CH Me CH-CH=CH, MeCH=CH- CH21Cl


OEt

Me CHCH=CH+ MeCH=CH-CH,OEt
Normal product Rearranged product
In general, there is greater number of by-products in the case of SNI reaction as compared to the
SN2 which is a one-step process involving nointemediate, hence, does not undergo rearrangement.
In fact, the formation of different products from a single substrate in a reaction which foliows the first
raeT is classic evidence that the reaction is proceeding through an
kinetics a
intermediate
4. No substitutions at bridgehead carbons: Substiution reactions under SNI conditions
either do not take place or proceed very slowiy at bridgehead carbons. SN2 reactions also fail with

KOHEtOH, Noreaction
Reflux, 21h
C1
330 ADVANCED ORGANIC CHEMISTRY

these substrates, ctions proceed


though for different reasons (Section 4.2). SNI through
arbocations which must be planar, Because of rigid cage like structures of the substrates, bridgehead
through
carbon atoms cannot assume planarity, hence. heterolvsis leading to the formation o carbocation is

also prevented. Consequently. bridgehead carbons are resistant towards substitution by the SNI
mechanism. For example. does not react on refluxing with KOH in
1-chloroapocamphane s0% 90
ethanol for 21 hours, although analogous open-chain systems react readily. However, it the rings are
iarge enough, SNI reactions should be possible, because nearly planar carbocation may be expected
nere.
example. [2. 2, 2]bicyclic systems undergo SNI reactions much faster than smaller bicyclic
ror
systems, though the reaction is still slower than with analogous open-chain systems. Thus, the
following rates were observed for solvolysis in 80% aqueous ethanol at 25°C:
Br

Br Br
Open chain system [2,2, 2]bicyclic system [2, 2, 1]bicyclic system
(1-butyl bromide) (1-bromobicyclo[2, 2, 2]octane) (1-bromo-7, 7-dimethyl
bicyclof2, 2, 1] heptane)
10-14
106
Rate:

You might also like