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:

Structure and SN2 Reactivity: The Substrate 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.