Alcohols and Phenols
Alcohols and Phenols
Chapter 17 Part 3
17.8 Oxidation of Alcohols Can be accomplished by inorganic reagents,
such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents
1
Oxidation of Primary Alcohols To aldehyde: pyridinium chlorochromate
(PCC, C5H6NCrO3Cl) in dichloromethane
Other reagents produce carboxylic acids
Converts secondary alcohol to ketone
2
CH3O
CH3OH CH3
PCC CH2Cl2, 25oC
O
CH3
O
Testosterone
4-Androstene-3,17-dione
Jones’ Reagent: CrO3 in aqueous sulfuric
acid.
Oxidizes primary alcohols to carboxylic acids:
CH3(CH2)8CH2OH 1-Decanol
O CrO3 CH3(CH2)8COH H2SO4 Decanoic acid
All of the oxidations occur via an E2 mechanism.
Mechanism of Chromic Acid Oxidation Alcohol forms a chromate ester followed by
elimination with electron transfer to give ketone The mechanism was determined by observing the
effects of isotopes on rates
3
Na2Cr2O7 in aqueous acetic acid is an
inexpensive oxidizing agent:
CH3
OH
Na2Cr2O7 acetic acid
4-tert-Methylcyclohexanol
CH3
O
4-tert-Methylcyclohexanone
What alcohols would give these products on oxidation? O
CH3 CH3CHCHO
O
What products would you expect from the oxidation of the following compounds with Jones’ reagent? With PCC? 1 -
Hexanol
Jones’: PCC:
2 -
Hexanol
Jones’: PCC:
Hexanal
Jones’: PCC:
4
Predict the major organic product: OH
K2Cr2O7 acetic acid
Cl
OH
PCC CH2Cl2
17.9 Protection of Alcohols Hydroxyl groups can easily transfer their proton to a
basic reagent This can prevent desired reactions Converting the hydroxyl to a (removable) functional
group without an acidic proton protects the alcohol
Methods to Protect Alcohols Reaction with chlorotrimethylsilane in the
presence of base yields an unreactive trimethylsilyl (TMS) ether The ether can be cleaved with acid or with fluoride ion to regenerate the alcohol
5
Protection -
Deprotection
6
17.10 Preparation and Uses of Phenols Industrial process from readily available
cumene Forms cumene hydroperoxide with oxygen at
high temperature
Laboratory Preparation of Phenols From aromatic sulfonic acids by melting with NaOH
at high temperature
Limited to the preparation of alkyl-substituted phenols
7
17.11 Reactions of Phenols The hydroxyl group is a strongly activating, making
phenols substrates for electrophilic halogenation, nitration, sulfonation, and Friedel–Crafts reactions Reaction of a phenol with strong oxidizing agents yields a quinone Fremy's salt [(KSO3)2NO] works under mild conditions through a radical mechanism
8
Quinones in Nature Ubiquinones mediate electron-transfer processes
involved in energy production through their redox reactions
17.12 Spectroscopy of Alcohols and Phenols Characteristic O–H stretching absorption at 3300 to
3600 cm−1 in the infrared Sharp absorption near 3600 cm-1 except if H-bonded:
then broad absorption 3300 to 3400 cm−1 range Strong C–O stretching absorption near 1050 cm−1
(See Figure 17.11) Phenol OH absorbs near 3500 cm-1
9
Butanol (Gas Phase)
Nuclear Magnetic Resonance Spectroscopy 13C NMR: C bonded to OH absorbs at a lower field, δ 50 to 80 1H NMR: electron-withdrawing effect of the nearby oxygen, absorbs at δ 3.5 to 4 (See Figure 17-13)
Usually no spin-spin coupling between O–H proton and neighboring protons on C due to exchange reactions with moisture or acids Spin–spin splitting is observed between protons on the oxygen-bearing carbon and other neighbors
Phenol O–H protons absorb at δ 3 to 8
10
11
Chapter 17 Part 3
17.8 Oxidation of Alcohols Can be accomplished by inorganic reagents,
such as KMnO4, CrO3, and Na2Cr2O7 or by more selective, expensive reagents
1
Oxidation of Primary Alcohols To aldehyde: pyridinium chlorochromate
(PCC, C5H6NCrO3Cl) in dichloromethane
Other reagents produce carboxylic acids
Converts secondary alcohol to ketone
2
CH3O
CH3OH CH3
PCC CH2Cl2, 25oC
O
CH3
O
Testosterone
4-Androstene-3,17-dione
Jones’ Reagent: CrO3 in aqueous sulfuric
acid.
Oxidizes primary alcohols to carboxylic acids:
CH3(CH2)8CH2OH 1-Decanol
O CrO3 CH3(CH2)8COH H2SO4 Decanoic acid
All of the oxidations occur via an E2 mechanism.
Mechanism of Chromic Acid Oxidation Alcohol forms a chromate ester followed by
elimination with electron transfer to give ketone The mechanism was determined by observing the
effects of isotopes on rates
3
Na2Cr2O7 in aqueous acetic acid is an
inexpensive oxidizing agent:
CH3
OH
Na2Cr2O7 acetic acid
4-tert-Methylcyclohexanol
CH3
O
4-tert-Methylcyclohexanone
What alcohols would give these products on oxidation? O
CH3 CH3CHCHO
O
What products would you expect from the oxidation of the following compounds with Jones’ reagent? With PCC? 1 -
Hexanol
Jones’: PCC:
2 -
Hexanol
Jones’: PCC:
Hexanal
Jones’: PCC:
4
Predict the major organic product: OH
K2Cr2O7 acetic acid
Cl
OH
PCC CH2Cl2
17.9 Protection of Alcohols Hydroxyl groups can easily transfer their proton to a
basic reagent This can prevent desired reactions Converting the hydroxyl to a (removable) functional
group without an acidic proton protects the alcohol
Methods to Protect Alcohols Reaction with chlorotrimethylsilane in the
presence of base yields an unreactive trimethylsilyl (TMS) ether The ether can be cleaved with acid or with fluoride ion to regenerate the alcohol
5
Protection -
Deprotection
6
17.10 Preparation and Uses of Phenols Industrial process from readily available
cumene Forms cumene hydroperoxide with oxygen at
high temperature
Laboratory Preparation of Phenols From aromatic sulfonic acids by melting with NaOH
at high temperature
Limited to the preparation of alkyl-substituted phenols
7
17.11 Reactions of Phenols The hydroxyl group is a strongly activating, making
phenols substrates for electrophilic halogenation, nitration, sulfonation, and Friedel–Crafts reactions Reaction of a phenol with strong oxidizing agents yields a quinone Fremy's salt [(KSO3)2NO] works under mild conditions through a radical mechanism
8
Quinones in Nature Ubiquinones mediate electron-transfer processes
involved in energy production through their redox reactions
17.12 Spectroscopy of Alcohols and Phenols Characteristic O–H stretching absorption at 3300 to
3600 cm−1 in the infrared Sharp absorption near 3600 cm-1 except if H-bonded:
then broad absorption 3300 to 3400 cm−1 range Strong C–O stretching absorption near 1050 cm−1
(See Figure 17.11) Phenol OH absorbs near 3500 cm-1
9
Butanol (Gas Phase)
Nuclear Magnetic Resonance Spectroscopy 13C NMR: C bonded to OH absorbs at a lower field, δ 50 to 80 1H NMR: electron-withdrawing effect of the nearby oxygen, absorbs at δ 3.5 to 4 (See Figure 17-13)
Usually no spin-spin coupling between O–H proton and neighboring protons on C due to exchange reactions with moisture or acids Spin–spin splitting is observed between protons on the oxygen-bearing carbon and other neighbors
Phenol O–H protons absorb at δ 3 to 8
10
11
