Chapter 22 (Substituted Benzenes)

• CBenzylic—H bonds are weaker (i.e. lower bond-dissociation energy) than Csp3—H bonds. • CBenzylic—H bonds are more acidic (i.e. lower pKa value) than Csp3—H bonds. These atypical Benzylic properties are caused by the resonance stabilization facilitated by the adjacent phenyl group.

Benzylic alcohols are more easily oxidized than standard alcohol-containing compounds. The oxidation of Benzylic alcohols requires the MnO2 oxidative reagent. (Jones Oxidation and PCC are too strong of oxidation processes to effectively oxidize the Benzylic alcohol group.)

Benzylic halides are more reactive in SN1 reactions than standard alkyl halides. This atypical Benzylic property is caused by the resonance stabilization facilitated by the adjacent phenyl group.

Radical Benzylic Halogenation

• X2, hv • X2, Δ

Halide Electrophilic Aromatic Substitution (Halide EAS)

• X2, FeX3 • X2, AlX3

• Electrophilic Aromatic Substitution is favored if a Lewis-acid catalyst is present. • Radical Halogenation is favored if heat (Δ) and/or light (hv) is added.

87 kcal/mol The relatively low BDE of CBenzylic—H bonds is brought about by the resonance stabilization of the resulting benzylic radical. (Conjugation with the π electrons of the adjacent phenyl group delocalizes the radical throughout the benzene ring.)

pKa ≈ 41 The relatively high acidity of CBenzylic—H bonds is brought about by the resonance stabilization of the resulting benzylic anion. (Conjugation with the π electrons of the adjacent phenyl group delocalizes the negative charge throughout the benzene ring.)

n–Butyl Lithium Deprotonation

n–Butyl Lithium, TMEDA n–Butyl Lithium = CH3CH2CH2CH2Li

n–Butyl Lithium is a strong base used to deprotonate CBenzylic—H bonds (and CAllylic—H bonds).

SN1 attack at the CarbonBenzylic creates the most stable addition product because the benzene’s aromaticity is maintained. SN1 attack at a cationic Carbon of another resonance form would create a less stable addition product because the benzene’s aromaticity would be destroyed.

Room-Temperature Jones Oxidation The room-temperature Jones Oxidation reaction cannot break C—C bonds.

Heated Jones Oxidation The heated Jones Oxidation reaction will break CBenzylic—C bonds.

• Na2Cr2O7, H2SO4 • CrO3, H2O, H2SO4

• KMnO4, Δ • H2O, H2SO4 • Na2Cr2O7, H2SO4, Δ • H2O, H2SO4

The CBenzylic—C bond is a weak C—C bond, so it is readily broken under the strong/unstable Jones Oxidation conditions.

MnO2 Oxidation

MnO2 Oxidation MnO2 is a mild oxidizing agent that only oxidizes CBenzylic—OH bonds (and CAllylic—OH bonds).

Benzylic Hydrogenolysis Benzylic Deprotection Typical CBenzylic—O bonds do not undergo Hydrogenolysis (within these conditions).

Benzylic Hydrogenolysis Benzylic Deprotection Typical CBenzylic—O bonds do not undergo Hydrogenolysis (within these conditions).

H2, Pd-C Any transition-metal catalyst can be used during the Benzylic Hydrogenolysis reaction (in place of Pd-C).