SN2 and E2 reactions

Zaitsev alkene product

more substituted, thermodynamic product

Hofmann alkene product

less substituted, kinetic product

S_N2 mechanism

substrate is attacked by the Lewis base acting as a nucleophile, forming a new σ-bond and breaking the old C-LG σ-bond at the same time

E2 mechanism

substrate is attacked by the Lewis base acting as a base, deprotonating the adjacent C-H bond, forming a new π-bond, and breaking the old C-LG σ-bond at the same time

S_N2/E2 reaction coordinate

• S_N and E reactions are usually exothermic

• S_N2 has lower activation energy barrier, but higher energy products

• E2 has higher activation energy barrier, but lower energy products

key features of S_N2 reactions

• bimolecular rate determining step (no carbocation formation)

• nucleophile must approach 180° from the C-LG bond

• inversion of configuration (sp³ carbon is turned inside out, not racemic)

• S_N2 preference with unhindered substrates (1°/2°)

key features of E2 reactions

• bimolecular rate determining step (no carbocation formation)

• C-H must have 180° dihedral angle to C-LG (anti-coplanar)

• π-bond forms between the two new, parallel p-orbitals

• Zaitsev alkene for strong, unhindered bases vs Hofmann alkene for strong, hindered bases

• E2 possible with all appropriate substrates

bulky strong bases (poor nucleophiles)

• ^-OtBu (alkoxides)

• LDA (^-NiPr₂)

considerations for basicity

• charge

• electronegativity

• influence of nearby inductive or resonance EWG/EDG

considerations for nucleophilicity

• charge

• electronegativity

• influence of nearby inductive or resonance EWG/EDG

• sterics (bulkiness)

• polarizability (large element anions are better nucleophiles than bases)

negatively charged Lewis bases

typically more reactive than neutral ones

neutral Lewis base

usually contains a nitrogen, oxygen, or sulfur

solvent preference for S_N2/E2

polar aprotic solvent (less efficient solvatation of anionic base is better)

S_N2 reactions with halide substrate

commonly performed under anionic conditions with good nucleophiles in aprotic solvents

S_N2 reactions with alcohol substrate

• nucleophile can come from a strong HX acid that has a nucleophilic conjugate base, a halogenating agent, or can be converted to a sulfonate

• OH is converted into a better leaving group before reaction

• performed under neutral conditions in aprotic solvent (halogenating/sulfonate)

strong acid S_N2 alcohol reaction

• acidic/aqueous

• alcohol to halide

• S_N1 or S_N2

PBr₃ S_N2 alcohol reaction

• non-aqueous (aprotic)

• alcohol to bromide

SOCl₂ S_N2 alcohol reaction

• non-aqueous (aprotic)

• alcohol to chloride

• S_N1 or S_N2 (pyridine)

ClSO₂R S_N2 alcohol reaction

• non-aqueous (aprotic)

• alcohol to sulfonate (pseudo halide)

E2 reactions with halide substrate

• dehydrohalogenation because there is a net removal of HX

• performed in anionic conditions (with strong base), at high temperatures

• depending on the base, Zaitsev or Hofmann elimination can be favoured

E2 reactions with alcohol substrate

• not possible

• acid-base reactions dominate when a strong base is added to an alcohol

• elimination reactions of alcohols must be done in strong acid using E1 mechanisms

factors that effect S_N2 and E2 reactions

• structure of the substrate

• concentration/nature of Lewis base (stronger are faster)

• nature of the leaving group (weaker bases are fastest)

• effect of the solvent (polar aprotic is fastest)

• temperature (higher temperature favours E2)