Free Radical Reactions: Notes by Nida

Advanced Organic Chemistry Notes

Covers Elimination, Pyrolytic, Free Radical, and Electrophilic Addition Reactions (Pages 1-47)

Pages 1-2

1. Stereochemistry of E2 Reaction

E2 reactions require a specific geometry for the proton and leaving group. The transition state is Anti-periplanar (Staggered, Dihedral angle 180°), which is lower energy than Syn-periplanar (Eclipsed, 0°).

Example: Meso-Stilbene Dibromide

\(\xrightarrow[\text{Base}]{E2}\)

Meso compound \(\xrightarrow{Anti-Elim}\) Cis-alkene.
(d,l) Pair \(\xrightarrow{Anti-Elim}\) Trans-alkene.

Cyclic Systems

In cyclohexane rings, E2 only occurs when H and LG are Trans-Diaxial.

\(\xrightarrow{E2}\)

\(\text{Alkene (Only if LG is Axial)}\)

Pages 3-5

2. E1 Elimination & Dehydration

Two-step process via Carbocation. First order kinetics: \( r = K[\text{Substrate}] \).

Dehydration of Alcohols

Reagents: Conc. \(H_2SO_4\), \(H_3PO_4\), \(P_2O_5\), \(POCl_3\), \(ThO_2\).

\(\xrightarrow{H^+}\)

\(\xrightarrow[-H_2O]{RDS}\)

\(\xrightarrow{Fast}\)

Regioselectivity

• Saytzeff Rule: Major product is the more substituted alkene (more stable).
• Bredt's Rule: Double bond cannot form at bridgehead carbon in small bicyclic systems (Planarity issue).

Pages 6-9

3. E1cB (Conjugate Base) Mechanism

Conditions: Poor Leaving Group (OH, OR, F) + Acidic \(\beta\)-Hydrogen + Electron Withdrawing Group (EWG).

General Mechanism

\(+ \text{Base} \rightleftharpoons\)

\(\xrightarrow{Slow}\)

Carbanion intermediate is stabilized by Resonance (-M) or Inductive (-I) effects.

Comparison Spectrum

• E1: Carbocation must be stable. Weak base.
• E2: Strong base. Simultaneous bond break/form.
• E1cB: Carbanion must be stable. Poor LG.

Pages 10-15

4. Kinetic Isotope Effect & Pyrolytic Elimination

Kinetic Isotope Effect (KIE)

\( \frac{k_H}{k_D} \approx 1 \) for E1 (Bond not broken in RDS).
\( \frac{k_H}{k_D} \approx 7 \) for E2 (Bond broken in RDS).

Pyrolytic Elimination (Ei)

Thermal elimination without external reagents. Proceeds via Syn-Elimination (Cyclic Transition State).

A. Chugaev Reaction (Xanthates)

\(\xrightarrow{1. CS_2/Base, 2. MeI}\)

\(\xrightarrow{\Delta}\)

B. Cope Elimination (Amine Oxides)

\(\xrightarrow[\text{Syn-Elim}]{\Delta}\)

\(+ \text{Hydroxylamine}\)

Pages 16-19

5. Free Radical Reactions

Initiated by heat, light (\(h\nu\)), or peroxides.

Peroxide Effect (Kharasch Effect)

Anti-Markovnikov addition of HBr to alkenes in presence of Peroxide.

\(+ HBr \xrightarrow{ROOR}\)

Selectivity of Halogenation

Reactivity order: \(F_2 > Cl_2 > Br_2 > I_2\).
Bromination is highly selective for 3° hydrogens ($1600 : 82 : 1$). Chlorination is less selective ($5 : 3.8 : 1$).

Pages 20-22

6. Radical Generation & Carriers

Initiator: AIBN decomposes to \(N_2\) + 2 Radicals.

Chain Carrier: Tributyltin Hydride (\(Bu_3SnH\)) is used to reduce alkyl halides.

\(+ Bu_3SnH \xrightarrow{AIBN}\)

Pages 23-30

7. Aromatic Substitution & Decarboxylation

Homolytic Aromatic Substitution

Radicals attack the benzene ring. Substituents affect orientation via Inductive/Mesomeric effects, but steric factors are significant.

Hunsdiecker Reaction

Silver salt of carboxylic acid + \(Br_2\) gives Alkyl Bromide (Decarboxylation).

\(+ Br_2 \xrightarrow{CCl_4, \Delta}\)

\(+ CO_2 + AgBr\)

Pages 31-35

8. NBS, Sandmeyer & Coupling

NBS (N-Bromosuccinimide)

Used for Allylic and Benzylic bromination.

\(+ \text{Allylic System} \xrightarrow{h\nu}\)

Sandmeyer Reaction

\(\xrightarrow{CuCl / HCl}\)

Pages 36-40

9. Auto-oxidation & Cumene Process

Cumene to Phenol

\(\xrightarrow{O_2}\)

\(\xrightarrow{H^+}\)

\(+ \text{Acetone}\)

Involves a phenyl migration rearrangement.

Pages 41-47

10. Electrophilic Addition to Alkenes

Stereochemistry

\(X_2\) addition is Anti. \(HX\) addition involves carbocation (rearrangement possible).

Ring Expansion

\(\xrightarrow{HCl}\)

Reaction driven by relief of ring strain and formation of stable carbocation.

Hydroboration-Oxidation

Syn-addition of H and OH. Anti-Markovnikov orientation.

\(\xrightarrow{1. BH_3, 2. H_2O_2/OH^-}\)