Nucleophilic Substitution Chapter 6 Nucleophilic Substitution

FunctIonal-Group TransformatIon by nucleophIlIc substItutIon Section 6.1 FunctIonal-Group TransformatIon by nucleophIlIc substItutIon

Nucleophilic Substitution Formation of alkyl halides from alcohols is a substitution process SN1: SN2: In these reactions halide serves as the nucleophile and H2O as the leaving group

Nucleophilic Substitution Alkyl halides undergo an analogous process with nucleophiles M+Y– Because the added reagent is nucleophilic, this is called nucleophilic substitution electrophile

The Nucleophile The nucleophile is typically a simple metal salt M+Y–, where M+ is Li+, K+, or Na+ The anion Y– can be any of a variety of organic or inorganic anions. Examples: Nucleophilicity is related in general to basicity, since nucleophiles are Lewis bases

The partially positive carbon reacts as a Lewis acid. The Electrophile The electrophile must contain a C–LG bond polarized towards LG, the leaving group Alkyl halides and pseudohalides (sulfonates) are most common The electrophilic carbon must be sp3 hybridized The partially positive carbon reacts as a Lewis acid.

RelatIve ReactIvIty of halIde LeavIng Groups Section 6.2 RelatIve ReactIvIty of halIde LeavIng Groups

Leaving Group Ability In a nucleophilic substitution reaction, the leaving group accepts electrons, just like an acid Good leaving groups –X are associated with strong acids HX Good leaving groups are also associated with weaker C–X bonds

The SN2 MechanIsm of NucleophIlIc SubstITutIon Section 6.3 The SN2 MechanIsm of NucleophIlIc SubstITutIon

Kinetics of SN2 Substitution of primary and methyl alcohols and primary and methyl halides is found to be bimolecular The rate law depends on the concentrations of both reactants Both reactants are involved in the rate-determining transition state In this TS, attack of the nucleophile and loss of the leaving group occur simultaneously

Reaction Coordinate Diagram

Stereochemistry of SN2 Studies of substitutions of optically active alkyl halides show that the nucleophile does not occupy the position where the leaving group was… SN2 occurs with inversion of configuration 100%! stereospecific

SterIc Effects and SN2 ReactIon Rates Section 6.4 SterIc Effects and SN2 ReactIon Rates

Steric Hindrance in the Electrophile Alkyl groups bound to the electrophilic carbon represent a hindrance toward backside attack of the nucleophile We observe this in the relative rates of SN2 for methyl, primary, secondary, and tertiary alkyl bromides The space “occupied” by the alkyl groups is called steric hindrance

Steric Hindrance in the Electrophile

The Neopentyl Effect: Adjacent Alkyl Groups Even alkyl groups adjacent to the electrophilic carbon slow the rate of SN2 This is often called the neopentyl effect because neopentyl halides react very slowly in SN2 neopentyl bromide