Leaving Groups • During SN1, SN2, E1, and E2 reactions, the leaving group begins to develop a negative charge as the transition state is reached. • Leaving groups that can better stabilize the developing negative charge reduce the energy of the transition state (lower Ea) and increase the rate of reaction. = SN1 + = SN2
Leaving Groups • The best leaving groups are weak bases: • I- > Br- > Cl- >> F- • alkanesulfonate ions: • Strongly basic ions rarely act as leaving groups: • OH- is a poor leaving group • H2O (a weak base) is a good leaving group • H- and R- never act as leaving groups
Solvent Effects • The solvent used during a nucleophilic substitution reaction can affect the relative strength of a nucleophile and the rate of reaction. • Polar protic solvent: • a solvent containing a hydrogen atom attached to a strongly electronegative element such as oxygen or nitrogen • capable of forming hydrogen bonds • water, alcohols
Solvent Effects • Polar aprotic solvents: • polar solvents that do not have a hydrogen atom attached to an atom of an electronegative element • DMF = dimethylformamide • DMSO = dimethylsulfoxide • HMPA = hexamethylphosphoramide
Solvent Effects • SN2Reactions: • Polar protic solvents form hydrogen bonds with nucleophiles and hinder their participation in substitution reactions. • Larger nucleophiles are more polarizable and less strongly solvated so nucleophile strength increases with increasing size: • I- > Br- > Cl- > F- • RSH > ROH • RS- > RO-
Solvent Effects • SN2Reactions: • Polar aprotic solvents solvate cations but cannot solvate the nucleophile due to steric hinderance. • “Naked” nucleophile (anion) is much stronger base and nucleophile. • Nucleophile strength parallels basicity (and is opposite of that observed using polar protic solvents) • F- > Cl- > Br- > I- • Reaction rate is significantly faster than using a polar protic solvent.