24.6 Sources of Phenols

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24.6Sources of Phenols

• Phenol is an important industrial chemical.
• Major use is in phenolic resins for adhesives
  and plastics.
• Annual U.S. production is about 4 billion pounds
  per year.

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IndustrialPreparationsof Phenol
1. NaOH heat
2. H
1. O2
1. NaOH heat
2. H2O H2SO4
2. H
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Laboratory Synthesis of Phenols

• from arylamines via diazonium ions

(81-86)
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24.7Naturally Occurring Phenols

• Many phenols occur naturally

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Example Thymol
OH
CH3
CH(CH3)2
Thymol(major constituent of oil of thyme)
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Example 2,5-Dichlorophenol
OH
Cl
Cl
2,5-Dichlorophenol(from defensive secretion ofa
species of grasshopper)
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24.8Reactions of PhenolsElectrophilic Aromatic
Substitution
Hydroxyl group strongly activates the ringtoward
electrophilic aromatic substitution
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Electrophilic Aromatic Substitution in Phenols

• Halogenation
• Nitration
• Nitrosation
• Sulfonation
• Friedel-Crafts Alkylation
• Friedel-Crafts Acylation

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Halogenation

Br2
(93)

• monohalogenation in nonpolar solvent(1,2-dichloro
  ethane)

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Halogenation
H2O

3Br2
25C
(95)

• multiple halogenation in polar solvent(water)

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Electrophilic Aromatic Substitution in Phenols

• Halogenation
• Nitration
• Nitrosation
• Sulfonation
• Friedel-Crafts Alkylation
• Friedel-Crafts Acylation

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Nitration
(73-77)

• OH group controls regiochemistry

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Electrophilic Aromatic Substitution in Phenols

• Halogenation
• Nitration
• Nitrosation
• Sulfonation
• Friedel-Crafts Alkylation
• Friedel-Crafts Acylation

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Nitrosation
NO
OH
(99)

• only strongly activated rings undergo
  nitrosation when treated with nitrous acid

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Electrophilic Aromatic Substitution in Phenols

• Halogenation
• Nitration
• Nitrosation
• Sulfonation
• Friedel-Crafts Alkylation
• Friedel-Crafts Acylation

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Sulfonation
H2SO4
100C
SO3H

• OH group controls regiochemistry

(69)
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Electrophilic Aromatic Substitution in Phenols

• Halogenation
• Nitration
• Nitrosation
• Sulfonation
• Friedel-Crafts Alkylation
• Friedel-Crafts Acylation

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Friedel-Crafts Alkylation

• (CH3)3COH reacts with H3PO4 to give (CH3)3C

(63)
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Electrophilic Aromatic Substitution in Phenols

• Halogenation
• Nitration
• Nitrosation
• Sulfonation
• Friedel-Crafts Alkylation
• Friedel-Crafts Acylation

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24.9Acylation of Phenols
Acylation can take place either on the ringby
electrophilic aromatic substitution or onoxygen
by nucleophilic acyl substitution
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Friedel-Crafts Acylation

ortho isomer
AlCl3

• under Friedel-Crafts conditions, acylation of the
  ring occurs(C-acylation)

(74)
(16)
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O-Acylation
(95)

• in the absence of AlCl3, acylation of the
  hydroxyl group occurs (O-acylation)

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O- versus C-Acylation
AlCl3
formed faster
more stable

• O-Acylation is kinetically controlled process
  C-acylation is thermodynamically controlled
• AlCl3 catalyzes the conversion of the aryl ester
  to the aryl alkyl ketones this is called the
  Fries rearrangement

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24.10Carboxylation of Phenols

• Aspirin and the Kolbe-Schmitt Reaction

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Aspirin is prepared from salicylic acid
H2SO4

• how is salicylic acid prepared?

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Preparation of Salicylic Acid
CO2
125C, 100 atm

• called the Kolbe-Schmitt reaction
• acidification converts the sodium salt
  shownabove to salicylic acid

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What Drives the Reaction?

• acid-base considerations provide an
  explanationstronger base on left weaker base
  on right

CO2
stronger base pKa of conjugate acid 10
weaker base pKa of conjugate acid 3
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Preparation of Salicylic Acid
CO2
125C, 100 atm

• how does carbon-carbon bond form?
• recall electron delocalization in phenoxide ion
• negative charge shared by oxygen and by
  the ring carbons that are ortho and para to
  oxygen

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Mechanism of ortho Carboxylation



C
O

O


H
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Mechanism of ortho Carboxylation

O




C
O
O



O


H
H
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Why ortho?Why not para?
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Why ortho?Why not para?
stronger base pKa of conjugate acid 4.5
weaker base pKa of conjugate acid 3
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Intramolecular Hydrogen Bondingin Salicylate Ion
Hydrogen bonding between carboxylate and
hydroxylgroup stabilizes salicylate ion.
Salicylate is less basic than para isomer and
predominates under conditionsof thermodynamic
control.