CH221 CLASS 20
CHAPTER 11: REACTIONS OF ALKYL HALIDES – SUBSTITUTION AND
ELIMINATION CONTINUED
Synopsis. This class discusses the second of the more common nucleophilic
substitution mechanisms – the SN1 reaction. Like in the previous class, the major
factors that influence the mechanism are considered in some detail. It will be helpful
to view classes 19 and 20 as complementary.
S Winstein, pioneer of carbocation chemistry
The SN1 Reaction
It has long been observed that, unlike primary and secondary alkyl halides, tertiary
halides, such as 2-bromo-2-methylpropane, readily hydrolyze in water (i.e. without
the need for a strong nucleophile, like OH-):
(CH3)3CBr
+
H2O

(CH3)3COH
+
HBr
Moreover, the kinetics of this reaction suggest that the mechanism is a multistep
reaction (more complex than SN2), whose rate determining step (slow step) does not
involve the nucleophile:
Rate = ko[RX]
The accepted mechanism for the above reaction is known as an S N1 reaction,
because it is a two-step process, with the slow, rate determining, step being the
initial ionization of the substrate. Hence it is a unimolecular nucleophilic substitution.
It is illustrated overleaf for the hydrolysis of (S)- 3-bromo-3-methylhexane.
It can be seen that ionization of the chiral (tetrahedral sp 3-hybridized) substrate
gives a planar sp2-hybridized carbocation intermediate, which is achiral. Attack of
nucleophilic water molecules on this intermediate can occur equally from left or right
to give a purely racemic product. In practice, this is rarely observed, because attack
usually occurs before the leaving group (bromide, here) has fully separated from the
carbocation (i.e. the two exist as an ion pair), giving a bias of attack from the left to
produce an excess of (R) (inverted) product. Nevertheless, SN1 reactions always
occur with a certain amount of racemization and the stereochemical result is very
different to that of the SN2 reactions, which occur with full inversion of configuration.
More will be said later of the part played by ion pairs in SN1 reactions.
The energy diagram that accompanies the above scheme is shown below.
Characteristics of the SN1 Reaction
Like the SN2 mechanism, the SN1 reaction is strongly influenced by several factors,
the most important of which this time are, structure of the substrate, identity of the
leaving group and the nature of the solvent. The identity of the nucleophile is
relatively unimportant in SN1 reactions, as will be shown later.
Influence of the Substrate
According to the Hammond postulate, any factor that stabilizes a high-energy
intermediate (the carbocation, here) also stabilizes the transition state that leads to it
(here that of the rate determining step 1):
The more stable the carbocation, the faster the SN1 reaction
We have seen already that a general order of stability of alkyl cations is 3 o > 2o > 1o
> CH3, the 3o cation being most effectively stabilized by hyperconjugation or +I
effects:
Branching at the reaction carbon favors the SN1 mechanism
To this list we can add allylic and benzylic substrates, because allyl and benzyl
cations are extensively stabilized by resonance.
In practice, primary allylic and primary benzylic substrates (like those above) react at
about the same rate as secondary alkyl substrates.
Steric effects are relatively unimportant in SN1 reactions, except in cases where the
carbocation is unable to achieve a planar configuration, as in certain strained ring
systems:
highly strained
nonplanar cation
+
Br
+
Br-
1-bromonorbornane
Influence of the Leaving Group
Because the leaving group is directly involved in the rate determining steps of S N1
reactions, an identical order of leaving group reactivity is observed for SN1 and SN2
reactions, viz.,
CN, OH, NH2, OR, F < H2O < Cl- < Br- < I- < TosOInfluence of the Nucleophile
Since the nucleophile is not involved in the rate determining step of S N1 reactions,
the influence of the nucleophile on reaction rate is minimal. Thus, 2-methyl-2propanol reacts with HX (X = Cl, Br, I) at about the same rate:
(CH3)3COH
+
HX

(CH3)3CX
+
H2O
Also, for the same reason, charged nucleophiles are no more effective than neutral
ones, so SN1 reactions are often carried out in acidic or neutral media.
Influence of the Solvent
SN1 reactions in which charge is created (the majority), are generally favored by
polar solvents, such as water. This is the exact opposite to solvent effects
experienced by SN2 reactions, many of which involve charge redistribution, rather
than charge creation. For the reaction below, note the data that follows.
(CH3)3C-Cl
+
ROH

(CH3)3C-OR
+
HCl
Solvent
100% ethanol
60% ethanol
40% water
20% ethanol
80% water
100% water
Rel. rate
1
100
1.4x10 4
105
The main reason for these observations is that polar solvents effectively stabilize the
carbocation intermediate. Hence, according to the Hammond postulate, polar
solvents also stabilize the transition state of the step leading to the carbocation – i.e.
the rate determining step. The solvation of a carbocation can be pictured below.
Hence, solvents influence SN1 reactions mainly by stabilization or destabilization of
the rate determining step transition state and the carbocation.
On the other hand, the main influence of solvents on SN2 reactions of the charge
redistribution type is on the ground state energy (stability) of the nucleophilic
reagent.
Ion Pair Formation
It is now known that ion pair formation is the major cause of the incomplete
racemization that is observed for most SN1 reactions. A typical example is the
hydrolysis of (R)-6-chloro-2,6-dimethyloctane, in water:
CH3
C2H5
C2H5 CH3
C
C+
Cl
C6H13
ion pair
Cl-
C6H13
(R)-6-chloro-2,6-dimethyl
octane
H2O
attack preferrentially
from left (less hindered)
-H+
HO
C
CH3
C2H5
CH3
C2H5
and
C6H13
60% (S) (inversion)
C
OH
C6H13
40% (R) (retention)
A general scheme for ion pair formation is
intimate
ion pair
R-X
R+ X-
R+ // X-
dissociated
(solvated) ions
R+ + X-
solvent
separated
ion pair
The presence of intimate ion pairs will result in the maximum amount of inversion
that accompanies racemization during an SN1 reaction.
Summary of SN1 Characteristics
Substrate. The best substrates yield the most stable carbocations. SN1 reactions
are best for tertiary allylic and benzylic halides.
Leaving Group. Good leaving groups (more stable anion) increase SN1 reaction
rates by lowering the transition state energy of the step that leads to carbocation
formation (the first, rate determining step).
Nucleophile. Neutral nucleophiles work well – a strong nucleophile is not needed.
Highly basic nucleophiles should be avoided because of competition from HX
elimination (E1 reaction – see last class)
Solvent. Polar solvents stabilize the carbocation intermediate by solvation, thus
increasing SN1 reaction rates.
Class Questions
1. Predict whether each of the following substitution reactions is likely to be S N1 or
SN2.
Cl
CH3COO
(a)
Secondary benzyl
substrate and aqueous
medium
SN1
CH3COO-Na+
CH3COOH, H2O
Br
(b)
OOCCH3
CH3COO-Na+
DMF
Primary substrate
and polar aprotic
medium
SN2
2. Rank the following in order of their expected SN1 reactivity.
CH3CH2Br, CH2=CHCH(Br)CH3, CH2=CHBr, CH3CH(Br)CH3
3
1
4
2
3. Optically pure 2,2-dimethyl –1-phenyl –1-propyl tosylate was heated with acetic
acid to yield the corresponding acetate, whose specific rotation, []D was + 5.3o.
If complete inversion had occurred, the optically pure acetate would have had
[]D = +53.6o. What percentage of inversion and what percentage of racemization
occurred in this reaction?
CH3 Ph
CH3
C
CH3
CH
CH3 Ph
HOAc
OTs
CH3
-TsOH
For 100% racemization, []D = 0.0o
For 100% inversion []D = 53.6o
Actual []D = 5.3o
_
% racemization = 53.6 5.3 x 100 = 90.1
53.6
% inversion = 9.9
C
CH3
CH
OAc