1. Chapter 22 Phenols
Dr. Wolf's CHM 201 & 202 2

2. Nomenclature
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3. 5-Chloro-2-methylphenol
Nomenclature OH
CH3 Cl
5-Chloro-2-methylphenol
named on basis of phenol as parent
substituents listed in alphabetical order
lowest numerical sequence: first point of difference rule
Dr. Wolf's CHM 201 & 202 3

4. Nomenclature OH OH OH 1,2-Benzenediol 1,3-Benzenediol 1,4-Benzenediol
(common name: pyrocatechol)
(common name: resorcinol)
(common name: hydroquinone)
Dr. Wolf's CHM 201 & 202 4

5. p-Hydroxybenzoic acid
Nomenclature OH
CO2H
p-Hydroxybenzoic acid
name on basis of benzoic acid as parent
higher oxidation states of carbon outrank hydroxyl group
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6. Structure and Bonding
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7. Structure of Phenol phenol is planar
C—O bond distance is 136 pm, which is slightly shorter than that of CH3OH (142 pm)
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8. Physical Properties
The OH group of phenols allows hydrogen bonding to other phenol molecules and to water.
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9. Hydrogen Bonding in Phenols
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10. Physical Properties (Table 24.1)
Compared to compounds of similar size and molecular weight, hydrogen bonding in phenol raises its melting point, boiling point, and solubility in water.
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11. Physical Properties (Table 24.1)
C6H5CH3
C6H5OH
C6H5F
Molecular weight 92 94 96
Melting point (°C)
–95 43
–41
Boiling point (°C,1 atm)
111
132 85
Solubility in H2O (g/100 mL,25°C)
0.05
8.2
0.2
Dr. Wolf's CHM 201 & 202 10

12. most characteristic property of phenols is their acidity
Acidity of Phenols
most characteristic property of phenols is their acidity
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13. Compare O H O – Ka = 10-10 + H + Ka = 10-16 CH3CH2O – CH3CH2O H + H +
• • •• O
• • •• –
Ka = 10-10 + H +
Ka = 10-16
CH3CH2O •• –
• •
CH3CH2O H •• + H +
Dr. Wolf's CHM 201 & 202 10

14. Delocalized negative charge in phenoxide ion– •• O
• •
• • H H H H H
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15. Delocalized negative charge in phenoxide ion– ••
• • O •• H – O
• •
• • H H H H H
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16. Delocalized negative charge in phenoxide ion
• • O •• H –
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17. Delocalized negative charge in phenoxide ion
• • O •• H –
• • O •• H –
Dr. Wolf's CHM 201 & 202 11

18. Delocalized negative charge in phenoxide ion
• • O •• H –
Dr. Wolf's CHM 201 & 202 11

19. Delocalized negative charge in phenoxide ion
• • O •• H – •• O
• • H – H •• H H H
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20. Phenols are converted to phenoxide ions in aqueous base
• • •• O
• • •• – HO – + +
H2O
stronger acid
weaker acid
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21. Substituent Effects on the Acidity of Phenols
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22. Electron-releasing groups have little or no effectOH OH
CH3 OH
OCH3
Ka:
1 x 10-10
5 x 10-11
6 x 10-11
Dr. Wolf's CHM 201 & 202 16

23. Electron-withdrawing groups increase acidityOH OH Cl OH
NO2
Ka:
1 x 10-10
4 x 10-9
7 x 10-8
Dr. Wolf's CHM 201 & 202 16

24. Effect of electron-withdrawing groups is most pronounced at ortho and para positionsOH
NO2 OH
NO2 OH
NO2
Ka:
6 x 10-8
4 x 10-9
7 x 10-8
Dr. Wolf's CHM 201 & 202 18

25. Effect of strong electron-withdrawing groups is cumulativeOH
NO2 OH
NO2 OH
NO2
O2N
Ka:
7 x 10-8
1 x 10-4
4 x 10-1
Dr. Wolf's CHM 201 & 202 19

26. Resonance Depiction O N H – + O N H – + • • •• • • •• 20
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27. Sources 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.
Dr. Wolf's CHM 201 & 202 1

28. Industrial Preparations of Phenol
SO3H Cl
CH(CH3)2
1. NaOH heat
2. H+
1. O2
1. NaOH heat OH
2. H2O H2SO4
2. H+
Dr. Wolf's CHM 201 & 202 2

29. Laboratory Synthesis of Phenols
from arylamines via diazonium ions
O2N
NH2
1. NaNO2, H2SO4, H2O
2. H2O, heat
O2N OH
(81-86%)
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30. Naturally Occurring Phenols
Many phenols occur naturally
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31. Thymol (major constituent of oil of thyme)
Example: Thymol OH
CH3
CH(CH3)2
Thymol (major constituent of oil of thyme)
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32. Example: 2,5-DichlorophenolOH Cl Cl
2,5-Dichlorophenol (from defensive secretion of a species of grasshopper)
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33. Reactions of Phenols: Electrophilic Aromatic Substitution
Hydroxyl group strongly activates the ring toward electrophilic aromatic substitution
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34. Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
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35. Halogenation OH OH ClCH2CH2Cl + Br2 0°C Br (93%)
monohalogenation in nonpolar solvent (1,2-dichloroethane)
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36. Halogenation OH F OH Br F H2O + 3Br2 25°C (95%)
multiple halogenation in polar solvent (water)
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37. Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
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38. Nitration OH CH3 OH CH3 NO2 HNO3 acetic acid 5°C (73-77%)
OH group controls regiochemistry
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39. Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202 2

40. Nitrosation NO OH OH NaNO2 H2SO4, H2O 0°C (99%)
only strongly activated rings undergo nitrosation when treated with nitrous acid
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41. Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202 2

42. Sulfonation OH CH3 H3C OH CH3 H3C H2SO4 100°C SO3H (69%)
OH group controls regiochemistry
(69%)
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43. Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202 2

44. Friedel-Crafts AlkylationOH
CH3 OH C
CH3
H3C
H3PO4 60°C
(CH3)3COH
(CH3)3COH reacts with H3PO4 to give (CH3)3C+
(63%)
Dr. Wolf's CHM 201 & 202 3

45. Electrophilic Aromatic Substitution in Phenols
Halogenation
Nitration
Nitrosation
Sulfonation
Friedel-Crafts Alkylation
Friedel-Crafts Acylation
Dr. Wolf's CHM 201 & 202 2

46. Acylation of Phenols
Acylation can take place either on the ring by electrophilic aromatic substitution or on oxygen by nucleophilic acyl substitution
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47. Friedel-Crafts AcylationOH OH C O
CH3
CH3CCl O +
ortho isomer
AlCl3
under Friedel-Crafts conditions, acylation of the ring occurs (C-acylation)
(74%)
(16%)
Dr. Wolf's CHM 201 & 202 3

48. O-Acylation O OH OC(CH2)6CH3 O + CH3(CH2)6CCl (95%)
in the absence of AlCl3, acylation of the hydroxyl group occurs (O-acylation)
Dr. Wolf's CHM 201 & 202 3

49. O- versus C-Acylation OC(CH2)6CH3 O OH C O (CH2)6CH3 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
Dr. Wolf's CHM 201 & 202 3

50. Carboxylation of Phenols
COH O
OCCH3
Aspirin and the Kolbe-Schmitt Reaction
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51. Aspirin is prepared from salicylic acid
COH O
OCCH3 O
CH3COCCH3
COH O OH
H2SO4
how is salicylic acid prepared?
Dr. Wolf's CHM 201 & 202 2

52. Preparation of Salicylic Acid
ONa
CONa O OH
CO2
125°C, 100 atm
called the Kolbe-Schmitt reaction
acidification converts the sodium salt shown above to salicylic acid
Dr. Wolf's CHM 201 & 202 3

53. What Drives the Reaction?
acid-base considerations provide an explanation: stronger base on left; weaker base on right O – ••
• • O – ••
• • C H +
CO2
• •
stronger base:
pKa of conjugate acid = 10
weaker base:
pKa of conjugate acid = 3
Dr. Wolf's CHM 201 & 202 3

54. Preparation of Salicylic Acid
ONa
CONa O OH
CO2
125°C, 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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55. – O O – H H O O – – H H • • •• • • •• • • •• • • •• 11
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56. Mechanism of ortho Carboxylation•• O H ••
• • –
• • •• C O – ••
• • C O
• • O
• • •• H
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57. Mechanism of ortho Carboxylation•• O
• • •• – •• C O
• • O – ••
• • C O ••
• • O
• • •• H H O – ••
• • C H
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58. Why ortho? Why not para? •• – O •• O H O H – – C C •• • • • • • • 6
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59. Why ortho? Why not para? •• – O •• O H O H – – C C •• stronger base:
• • – O – ••
• • C H O •• H C
• • –
weaker base:
pKa of conjugate acid = 3
stronger base:
pKa of conjugate acid = 4.5
Dr. Wolf's CHM 201 & 202 6

60. Intramolecular Hydrogen Bonding in Salicylate Ion– H
Hydrogen bonding between carboxylate and hydroxyl group stabilizes salicylate ion. Salicylate is less basic than para isomer and predominates under conditions of thermodynamic control.
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61. Preparation of Aryl Ethers
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62. Typical Preparation is by Williamson Synthesis
ONa
SN2 OR + RX +
NaX
Dr. Wolf's CHM 201 & 202 2

63. Typical Preparation is by Williamson Synthesis
ONa
SN2 OR + RX +
NaX
but the other combination X +
RONa
fails because aryl halides are normally unreactive toward nucleophilic substitution
Dr. Wolf's CHM 201 & 202 2

64. Example
ONa
acetone
OCH3 +
CH3I
heat
(95%)
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65. Example OH + H2C CHCH2Br K2CO3 acetone, heat (86%) OCH2CH CH2 3
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66. Aryl Ethers from Aryl Halides
NO2
OCH3
NO2
CH3OH +
KOCH3 + KF
25°C
(93%)
nucleophilic aromatic substitution is effective with nitro-substituted (ortho and/or para) aryl halides
Dr. Wolf's CHM 201 & 202 5

67. Cleavage of Aryl Ethers by Hydrogen Halides
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68. Cleavage of Alkyl Aryl Ethers+ •• H Br ••
• • ••
• • Br – ••
• • O + + R
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69. Cleavage of Alkyl Aryl Ethers+ •• ••
• • H Br ••
• • ••
• • Br – O + + R
An alkyl halide is formed; never an aryl halide! O Ar •• H R Br ••
• • +
Dr. Wolf's CHM 201 & 202 7

70. Example OCH3 OH OH HBr + CH3Br heat (85-87%) (57-72%) 9
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71. Claisen Rearrangement of Allyl Aryl Ethers
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72. Allyl Aryl Ethers Rearrange on Heating
OCH2CH
CH2
allyl group migrates to ortho position
200°C OH
CH2CH
CH2
(73%)
Dr. Wolf's CHM 201 & 202 2

73. keto-to-enol isomerization
Mechanism
OCH2CH
CH2 O
rewrite as
keto-to-enol isomerization OH O H
Dr. Wolf's CHM 201 & 202 3

74. Sigmatropic Rearrangement
Claisen rearrangement is an example of a sigmatropic rearrangement. A  bond migrates from one end of a conjugated  electron system to the other.
this  bond breaks O O H
“conjugated  electron system” is the allyl group
this  bond forms
Dr. Wolf's CHM 201 & 202

75. Oxidation of Phenols: Quinones
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76. Quinones
The most common examples of phenol oxidations are the oxidations of 1,2- and 1,4-benzenediols to give quinones. OH O
Na2Cr2O7, H2SO4
H2O
(76-81%)
Dr. Wolf's CHM 201 & 202

77. Quinones
The most common examples of phenol oxidations are the oxidations of 1,2- and 1,4-benzenediols to give quinones. OH
CH3 O
CH3 O
Ag2O
diethyl ether
(68%)
Dr. Wolf's CHM 201 & 202

78. Alizarin (red pigment)
Some quinones are dyes O OH
Alizarin (red pigment)
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79. Some quinones are important biomolecules
CH3O O
CH3 n
Ubiquinone (Coenzyme Q)
n = 6-10
involved in biological electron transport
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80. Some quinones are important biomolecules
CH3
Vitamin K
(blood-clotting factor)
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81. Spectroscopic Analysis of Phenols
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82. Infrared Spectroscopy
infrared spectra of phenols combine features of alcohols and aromatic compounds
O—H stretch analogous to alcohols near cm-1
C—O stretch at cm-1
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83. Figure 24.3: Infrared Spectrum of p-Cresol
CH3 OH
C—H
O—H
C—O
2000
3500
3000
2500
1000
1500
500
Wave number, cm-1
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84. 1H NMR
Hydroxyl proton of OH group lies between alcohols and carboxylic acids; range is ca.  4-12 ppm (depends on concentration). For p-cresol the OH proton appears at  5.1 ppm (Figure 24.4).
CH3 HO H
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85. H HO CH3 Chemical shift (, ppm) 1 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Chemical shift (, ppm)
Dr. Wolf's CHM 201 & 202 1

86. 13C NMR
CH3 OH
139.8
21.3
129.4
112..3
116.1
155.1
121.7
Oxygen of hydroxyl group deshields carbon to which it is directly attached.
The most shielded carbons of the ring are those that are ortho and para to the oxygen.
Dr. Wolf's CHM 201 & 202

87. UV-VIS
Oxygen substitution on ring shifts max to longer wavelength; effect is greater in phenoxide ion. – OH O
max
204 nm
256 nm
210 nm
270 nm
235 nm
287 nm
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88. Mass Spectrometry
Prominent peak for molecular ion. Most intense peak in phenol is for molecular ion. OH •+ ••
m/z 94
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89. End of Chapter 22
Dr. Wolf's CHM 201 & 202