Increasing polarizability improves nucleophilic
power.
The degree of nucleophilicity increases down the periodic table,
even for uncharged nucleophiles, for which the solvent effects
would be much weaker.
H2Se > H2S > H2O, and PH3 > NH3
This effect is due to the
larger polarizability of the
larger atom at the bottom
of the periodic table
The larger electron clouds
allow for more effective
overlap in the SN2
transition state.
Sterically hindered nucleophiles are poorer
reagents.
Nucleophiles having large bulky substituents are not as reactive
as unhindered nucleophiles:
Sterically bulky nucleophiles react more slowly.
Nucleophilic substitutions may be reversible.
Halide ions (except F-) are both good nucleophiles and good
leaving groups.
The SN2 reactions of these halides are reversible.
The solubility of the sodium halides dramatically decreases in the
order: NaI > NaBr > NaCl.
NaCl is virtually insoluble in propanone so reactions involving the
displacment of Cl- can be made go to completion by using the
sodium salt of the attacking nucleophile:
When the nucleophile in a SN2 reaction is a strong base (HO-,
CH3O-, etc.) it becomes a very poor leaving group, and SN2
reactions involving strong bases as nucleophiles are essentially
irreversible.
The relative
reaction rate of
iodomethane
with a variety of
nucleophiles
illustrates the
previous points:
6-9
Structure and SN2 Reactivity: The Substrate
Branching at the reacting carbon decreases the rate
of the SN2 reaction.
The effects of substituents on the reacting carbon can be seen in
the following data:
The transition states of the reaction of OH- with methyl, primary,
secondary and tertiary carbon centers explain the decrease in
activity:
The steric hindrance caused by adding successive methyl groups
to the electrophilic carbon decreases the transition state stability
to the point that substitution at a tertiary carbon does not occur
at all.
(fast) Methyl > primary > secondary > tertiary (does not occur)
(very slow)
Lengthening the chain by one or two carbons
reduces SN2 reactivity.
Replacement of one hydrogen in chloromethane by a methyl
group to form chloroethane reduces the rate of SN2 displacement
of the chlorine atom by about a factor of 100.
Replacement of the hydrogen by an ethyl group to form
chloropropane reduces the rate of SN2 displacement of the
chlorine atom by another factor of 2.
The gauche conformer
in the 1-propyl case
has similar reactivity
to the ethyl case.
Replacement of a hydrogen in a halomethane by a carbon chain of
3 or more atoms shows no additional effect over a carbon chain of
2 atoms.
Branching next to the reacting carbon also retards
substitution.
Multiple substitution at the position
next to the electrophilic carbon causes
a dramatic decrease in reactivity in SN2
substitution reactions.
1-Bromo-2,2-dimethylpropane is
virtually inert.
The explanation for the decrease in reactivity is in the stabilities
of the transition states involved:
In 1-bromo-2-methylpropane two gauche methyl-halide
interactions occur in the only conformation permitting nucleophilic
attach by the OH-.
In 1-bromo-2,2-dimethylpropane there is no conformation
allowing easy approach of the OH- and the reaction is blocked
almost completely.