Nucleophilic Substitution

Organic Substitution versus Inorganic Single Replacement Oxidation-reduction, with new ionic bonds, in single replacement Making and breaking covalent bonds in organic substitution

Aromatic and Acyl Substitution Addition/elimination that reconstitutes aromatic system Addition/elimination that reconstitutes carbonyl group

Radical Substitution

Nucleophilic Substitution Bimolecular Nucleophilic Substitution (SN2) Second Order with Inversion Unimolecular Nucleophilic Substitution (SN1) First Order with Racemization

SN2 Inversion versus SN1 Racemization Stereospecific SN1 Racemization Loss of optical purity

Kinetics of SN2 versus SN1 Rate = k[Substrate][Nucleophile] Rate depends on nucleophile conc. Restrictive collision orientation in RDS SN1 Rate = k[Substrate] Rate independent of nucleophile conc. Net bond dissociation in RDS

Kinetic Control versus Thermodynamic Control

Steric Hindrance versus Carbocation Stability Less hindered substrate favors SN2 More stable carbocation favors SN1

Protic Solvents for SN2 versus SN1 Nucleophile stabilized in SN2 Charged intermediates stabilized in SN1

Protic versus Aprotic Solvents

Effect of Nucleophile SN2 could be favored with superior nucleophiles: Localized, destabilized anion Low electronegativity atom Larger, more polarizable atom High p-character hybrid orbital Low steric hindrance

Factors Favoring SN2 versus SN1 Less hindered substrates favor SN2; substrates with more stable carbocation intermediates favor SN1. Polar aprotic solvents, which avoid sequestration of nucleophiles, are favored for SN2; protic solvents, which stabilize intermediates, are favored for SN1. Exceptional nucleophiles may improve the preference for SN2 over SN1.