Chapter 06

Phenols and Aryl Halides: Nucleophilic

Aromatic Substitution
 Structure and Nomenclature of Phenols
 Phenols have hydroxyl groups bonded directly to a benzene ring
 Naphthols and phenanthrols have a hydroxyl group bonded to a polycyclic
benzenoid ring

Chapter 6 2
 Nomenclature of Phenols
 Phenol is the parent name for the family of hydroxybenzenes
 Methylphenols are called cresols

Chapter 6 3
 Synthesis of Phenols
 Laboratory Synthesis
 Phenols can be made by hydrolysis of arenediazonium salts

Chapter 6 4
 Industrial Syntheses
 1. Hydrolysis of Chlorobenzene (Dow Process)
 Chlorobenzene is heated with sodium hydroxide under high pressure
 The reaction probably proceeds through a benzyne intermediate (Section 21.11B)

 2. Alkali Fusion of Sodium Benzenesulfonate

 Sodium benzenesulfonate is melted with sodium hydroxide

Chapter 6 5
 3. From Cumene Hydroperoxide
Benzene and propene are the starting materials for a three-step sequence that produces
phenol and acetone. Most industrially synthesized phenol is made by this method

Chapter 6 6
 Reactions of Phenols as Acids
 Strength of Phenols as Acids
 Phenols are much stronger acids than alcohols

Chapter 6 7
 Phenol is much more acidic than cyclohexanol

 Experimental results show that the oxygen of a phenol is more

positive and this makes the attached hydrogen more acidic
 The oxygen of phenol is more positive because it is attached to an electronegative
sp2 carbon of the benzene ring
 Resonance contributors to the phenol molecule also make the oxygen more
positive

Chapter 6 8
 Distinguishing and Separating Phenols from Alcohols and
Carboxylic Acids
 Phenols are soluble in aqueous sodium hydroxide because of their
relatively high acidity
 Most alcohols are not soluble in aqueous sodium hydroxide
 A water-insoluble alcohol can be separated from a phenol by extracting the phenol into
aqueous sodium hydroxide

 Phenols are not acidic enough to be soluble in aqueous sodium

bicarbonate (NaHCO3)
 Carboxylic acids are soluble in aqueous sodium bicarbonate
 Carboxylic acids can be separated from phenols by extracting the carboxylic acid into
aqueous sodium bicarbonate

Chapter 6 9
 Other Reactions of the O-H Group of Phenols
 Phenols can be acylated with acid chlorides and anhydrides

Chapter 6 10
 Phenols in the Williamson Ether Synthesis
 Phenoxides (phenol anions) react with primary alkyl halides to
form ethers by an SN2 mechanism

Chapter 6 11
 Cleavage of Alkyl Aryl Ethers
 Reaction of alkyl aryl ethers with HI or HBr leads to an alkyl halide
and a phenol
 Recall that when a dialkyl ether is reacted, two alkyl halides are produced

Chapter 6 12
 Reaction of the Benzene Ring of Phenols
 Bromination
 The hydroxyl group is a powerful ortho, meta director and usually
the tribromide is obtained
 Monobromination can be achieved in the presence of carbon disulfide at low
temperature

 Nitration
 Nitration produces o- and p-nitrophenol
 Low yields occur because of competing oxidation of the ring

Chapter 6 13
 Sulfonation
 Sulfonation gives mainly the the ortho (kinetic) product at low
temperature and the para (thermodynamic) product at high
temperature

Chapter 6 14
 The Kolbe Reaction
 Carbon dioxide is the electrophile for an electrophilic aromatic
substitution with phenoxide anion
 The phenoxide anion reacts as an enolate
 The initial keto intermediate undergoes tautomerization to the phenol product
 Kolbe reaction of sodium phenoxide results in salicyclic acid, a synthetic
precursor to acetylsalicylic acid (aspirin)

Chapter 6 15
 The Claisen Rearrangement
 Allyl phenyl ethers undergo a rearrangement upon heating that
yields an allyl phenol
 The process is intramolecular; the allyl group migrates to the
aromatic ring as the ether functional group becomes a ketone
 The unstable keto intermediate undergoes keto-enol tautomerization to give the
phenol group
 The reaction is concerted, i.e., bond making and bonding breaking
occur at the same time

Chapter 6 16
 Quinones
 Hydroquinone is oxidized to p-benzoquinone by mild oxidizing
agents
 Formally this results in removal of a pair of electrons and two protons from
hydroquinone
 This reaction is reversible

 Every living cell has ubiquinones (Coenzymes Q) in the inner

mitochondrial membrane
 These compounds serve to transport electrons between substrates in enzyme-
catalyzed oxidation-reduction reactions

Chapter 6 17
 Aryl Halides and Nucleophilic Aromatic
Substitution

Chapter 6 18
 SN2 reaction also doesn’t occur in aryl (and vinyl halides) because
the carbon-halide bond is shorter and stronger than in alkyl
halides
 Bonds to sp2-hybridized carbons are shorter, and therefore stronger, than to
sp3-hybridized carbons
 Resonance gives the carbon-halogen bond some double bond character

Chapter 6 19
 Nucleophilic Aromatic Substitution by Addition-
Elimination: The SNAr Mechanism
 Nucleophilic substitution can occur on benzene rings when strong
electron-withdrawing groups are ortho or para to the halogen atom
 The more electron-withdrawing groups on the ring, the lower the temperature
required for the reaction to proceed

Chapter 6 20
 Nucleophilic Aromatic Substitution through an
Elimination-Addition Mechanism: Benzyne
 Under forcing conditions, chlorobenzene can undergo an apparent
nucleophilic substitution with hydroxide
 Bromobenzene can react with the powerful base amide

Chapter 6 21
 The reaction proceeds by an elimination-addition mechanism
through the intermediacy of a benzyne (benzene containing a triple
bond)

Chapter 6 22