Dr. Wolf's CHM 201 & 202 22 - 1 Chapter 22 Chapter 22 Phenols Phenols
Jan 19, 2016
Dr. Wolf's CHM 201 & 202 22 - 1
Chapter 22Chapter 22PhenolsPhenols
Chapter 22Chapter 22PhenolsPhenols
Dr. Wolf's CHM 201 & 202 22 - 2
NomenclatureNomenclatureNomenclatureNomenclature
Dr. Wolf's CHM 201 & 202 22 - 3
named on basis of phenol as parentnamed on basis of phenol as parent
substituents listed in alphabetical ordersubstituents listed in alphabetical order
lowest numerical sequence: first point oflowest numerical sequence: first point ofdifference ruledifference rule
5-5-ChloroChloro-2--2-methylmethylphenolphenol
NomenclatureNomenclatureNomenclatureNomenclature OHOH
CHCH33
ClCl
Dr. Wolf's CHM 201 & 202 22 - 4
NomenclatureNomenclatureNomenclatureNomenclature OHOH
OHOH
1,2-Benzenediol1,2-Benzenediol
OHOH
OHOH
OHOH
OHOH
1,3-Benzenediol1,3-Benzenediol 1,4-Benzenediol1,4-Benzenediol
(common name:(common name:pyrocatechol)pyrocatechol)
(common name:(common name:resorcinol)resorcinol)
(common name:(common name:hydroquinone)hydroquinone)
Dr. Wolf's CHM 201 & 202 22 - 5
name on basis of benzoic acid as parentname on basis of benzoic acid as parent
higher oxidation states of carbon outrankhigher oxidation states of carbon outrankhydroxylhydroxyl group group
NomenclatureNomenclatureNomenclatureNomenclature
pp-Hydroxybenzoic acid-Hydroxybenzoic acid
OHOH
COCO22HH
Dr. Wolf's CHM 201 & 202 22 - 6
Structure and BondingStructure and BondingStructure and BondingStructure and Bonding
Dr. Wolf's CHM 201 & 202 22 - 7
phenol is planarphenol is planar
C—O bond distance is 136 pm, which isC—O bond distance is 136 pm, which isslightly shorter than that of CHslightly shorter than that of CH33OH (142 pm)OH (142 pm)
Structure of PhenolStructure of PhenolStructure of PhenolStructure of Phenol
Dr. Wolf's CHM 201 & 202 22 - 8
The OH group of phenols allows hydrogen bondingThe OH group of phenols allows hydrogen bondingto other phenol molecules and to water.to other phenol molecules and to water.
Physical PropertiesPhysical PropertiesPhysical PropertiesPhysical Properties
Dr. Wolf's CHM 201 & 202 22 - 9
HH OOOO
Hydrogen Bonding in PhenolsHydrogen Bonding in PhenolsHydrogen Bonding in PhenolsHydrogen Bonding in Phenols
Dr. Wolf's CHM 201 & 202 22 - 10
Compared to compounds of similar size andCompared to compounds of similar size andmolecular weight, hydrogen bonding in phenol molecular weight, hydrogen bonding in phenol raises its melting point, boiling point, andraises its melting point, boiling point, andsolubility in water.solubility in water.
Physical Properties (Table 24.1)Physical Properties (Table 24.1)Physical Properties (Table 24.1)Physical Properties (Table 24.1)
Dr. Wolf's CHM 201 & 202 22 - 11
Physical Properties (Table 24.1)Physical Properties (Table 24.1)Physical Properties (Table 24.1)Physical Properties (Table 24.1)
CC66HH55CHCH33 CC66HH55OHOH CC66HH55FF
Molecular weightMolecular weight 9292 9494 9696
––9595 4343 ––4141Melting point (°C)Melting point (°C)
BoilingBoilingpoint (°C,1 atm)point (°C,1 atm)
111111 132132 8585
Solubility inSolubility inHH22O (g/100 mL,25°C)O (g/100 mL,25°C)
0.050.05 8.28.2 0.20.2
Dr. Wolf's CHM 201 & 202 22 - 12
Acidity of PhenolsAcidity of Phenols
most characteristic property of most characteristic property of phenols is their acidityphenols is their acidity
Dr. Wolf's CHM 201 & 202 22 - 13
CompareCompareCompareCompare OO HH••••••••
KKaa = 10 = 10-10-10
++HH ++
OO•••••••• ••••
––
CHCH33CHCH22OO HH••••
••••
KKaa = 10 = 10-16-16
++HH ++ CHCH33CHCH22OO••••
••••
––••••
Dr. Wolf's CHM 201 & 202 22 - 14
Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion
••••OO••••
HH
HH
HH
HH
HH
••••––
Dr. Wolf's CHM 201 & 202 22 - 15
Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion
••••OO••••
HH
HH
HH
HH
HH
••••–– ••••OO
••••
HH
HH
HH
HH
HH
––••••
Dr. Wolf's CHM 201 & 202 22 - 16
Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion ••••OO••••
HH
HH
HH
HH
HH
––••••
Dr. Wolf's CHM 201 & 202 22 - 17
Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion ••••OO••••
HH
HH
HH
HH
HH
––•••• ••••OO
••••
HH
HH
HH
HH
HH––••••
Dr. Wolf's CHM 201 & 202 22 - 18
Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion ••••OO••••
HH
HH
HH
HH
HH––••••
Dr. Wolf's CHM 201 & 202 22 - 19
Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion
••••OO••••
HH
HH
HH
HH
HH
––••••
••••OO••••
HH
HH
HH
HH
HH––••••
Dr. Wolf's CHM 201 & 202 22 - 20
Phenols are converted to phenoxide ionsPhenols are converted to phenoxide ionsin aqueous basein aqueous base
Phenols are converted to phenoxide ionsPhenols are converted to phenoxide ionsin aqueous basein aqueous base OO HH••••
•••• OO•••••••• ••••
––
++ HOHO–– ++ HH22OO
stronger acidstronger acid weaker acidweaker acid
Dr. Wolf's CHM 201 & 202 22 - 21
Substituent EffectsSubstituent Effectson theon the
Acidity of PhenolsAcidity of Phenols
Substituent EffectsSubstituent Effectson theon the
Acidity of PhenolsAcidity of Phenols
Dr. Wolf's CHM 201 & 202 22 - 22
Electron-releasing groups have little or no effectElectron-releasing groups have little or no effectElectron-releasing groups have little or no effectElectron-releasing groups have little or no effect OHOH
CHCH33
OHOH OHOH
OCHOCH33
KKaa:: 1 x 101 x 10-10-10 5 x 105 x 10-11-11 6 x 106 x 10-11-11
Dr. Wolf's CHM 201 & 202 22 - 23
Electron-withdrawing groups increase acidityElectron-withdrawing groups increase acidityElectron-withdrawing groups increase acidityElectron-withdrawing groups increase acidity OHOH
ClCl
OHOH OHOH
NONO22
KKaa:: 1 x 101 x 10-10-10 4 x 104 x 10-9-9 7 x 107 x 10-8-8
Dr. Wolf's CHM 201 & 202 22 - 24
Effect of electron-withdrawing groups is mostEffect of electron-withdrawing groups is mostpronounced at ortho and para positionspronounced at ortho and para positions
Effect of electron-withdrawing groups is mostEffect of electron-withdrawing groups is mostpronounced at ortho and para positionspronounced at ortho and para positions OHOH
NONO22
OHOH
NONO22
OHOH
NONO22
KKaa:: 6 x 106 x 10-8-8 4 x 104 x 10-9-9 7 x 107 x 10-8-8
Dr. Wolf's CHM 201 & 202 22 - 25
Effect of strong electron-withdrawing groupsEffect of strong electron-withdrawing groupsis cumulativeis cumulative
Effect of strong electron-withdrawing groupsEffect of strong electron-withdrawing groupsis cumulativeis cumulative OHOH
NONO22
OHOH
NONO22
NONO22
OHOH
NONO22
NONO22
OO22NN
KKaa:: 7 x 107 x 10-8-8 1 x 101 x 10-4-4 4 x 104 x 10-1-1
Dr. Wolf's CHM 201 & 202 22 - 26
Resonance DepictionResonance DepictionResonance DepictionResonance Depiction
••••OO••••
NN
HH
HH
HH
HH
••••OO OO
••••
••••
•••••••••••• ––
++
••••
––
••••OO••••
NN
HH
HH
HH
HH
••••
––
OO OO
••••
••••
•••••••••••• ––
++
Dr. Wolf's CHM 201 & 202 22 - 27
Sources of PhenolsSources of PhenolsSources of PhenolsSources of Phenols
Phenol is an important industrial chemical.Phenol is an important industrial chemical.
Major use is in phenolic resins for adhesives Major use is in phenolic resins for adhesives and plastics.and plastics.
Annual U.S. production is about 4 billion Annual U.S. production is about 4 billion pounds per year.pounds per year.
Dr. Wolf's CHM 201 & 202 22 - 28
1. NaOH 1. NaOH heat heat
2. H2. H++
1. NaOH 1. NaOH heat heat
2. H2. H++1. O1. O22
2. H2. H22OO
H H22SOSO44
IndustrialIndustrial
PreparationsPreparations
of Phenolof Phenol
IndustrialIndustrial
PreparationsPreparations
of Phenolof Phenol
SOSO33HH
ClCl
CH(CHCH(CH33))22
OHOH
Dr. Wolf's CHM 201 & 202 22 - 29
(81-86%)(81-86%)
OO22NN
NNHH22
OO22NN
OOHH
1.1. NaNONaNO22,,
HH22SOSO44,,
HH22OO
2.2. HH22O, heatO, heat
Laboratory Synthesis of PhenolsLaboratory Synthesis of PhenolsLaboratory Synthesis of PhenolsLaboratory Synthesis of Phenols
from arylamines via diazonium ionsfrom arylamines via diazonium ions
Dr. Wolf's CHM 201 & 202 22 - 30
Naturally Occurring PhenolsNaturally Occurring PhenolsNaturally Occurring PhenolsNaturally Occurring Phenols
Many phenols occur naturallyMany phenols occur naturally
Dr. Wolf's CHM 201 & 202 22 - 31
CH(CHCH(CH33))22
OHOH
CHCH33
ThymolThymol
(major constituent of oil of thyme)(major constituent of oil of thyme)
Example: ThymolExample: ThymolExample: ThymolExample: Thymol
Dr. Wolf's CHM 201 & 202 22 - 32
ClCl
OHOH
ClCl
2,5-Dichlorophenol2,5-Dichlorophenol
(from defensive secretion of(from defensive secretion of
a species of grasshopper)a species of grasshopper)
Example: 2,5-DichlorophenolExample: 2,5-DichlorophenolExample: 2,5-DichlorophenolExample: 2,5-Dichlorophenol
Dr. Wolf's CHM 201 & 202 22 - 33
Reactions of Phenols:Reactions of Phenols:
Electrophilic Aromatic Electrophilic Aromatic
SubstitutionSubstitution
Reactions of Phenols:Reactions of Phenols:
Electrophilic Aromatic Electrophilic Aromatic
SubstitutionSubstitution
Hydroxyl group strongly activates the ringHydroxyl group strongly activates the ringtoward electrophilic aromatic substitutiontoward electrophilic aromatic substitution
Dr. Wolf's CHM 201 & 202 22 - 34
HalogenationHalogenation
NitrationNitration
NitrosationNitrosation
SulfonationSulfonation
Friedel-Crafts AlkylationFriedel-Crafts Alkylation
Friedel-Crafts AcylationFriedel-Crafts Acylation
Electrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in Phenols
Dr. Wolf's CHM 201 & 202 22 - 35
HalogenationHalogenationHalogenationHalogenation
monohalogenation in nonpolar solventmonohalogenation in nonpolar solvent(1,2-dichloroethane)(1,2-dichloroethane)
++ BrBr22
ClCHClCH22CHCH22ClCl
0°C0°C
OOHH OOHH BrBr
(93%)(93%)
Dr. Wolf's CHM 201 & 202 22 - 36
HalogenationHalogenationHalogenationHalogenation
multiple halogenation in polar solventmultiple halogenation in polar solvent(water)(water)
++ 3Br3Br22
HH22OO
25°C25°C
OOHH FF
OOHH
BrBr
BrBrBrBr
FF
(95%)(95%)
Dr. Wolf's CHM 201 & 202 22 - 37
HalogenationHalogenation
NitrationNitration
NitrosationNitrosation
SulfonationSulfonation
Friedel-Crafts AlkylationFriedel-Crafts Alkylation
Friedel-Crafts AcylationFriedel-Crafts Acylation
Electrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in Phenols
Dr. Wolf's CHM 201 & 202 22 - 38
NitrationNitrationNitrationNitration
HNOHNO33
acetic acidacetic acid5°C5°C
(73-77%)(73-77%)OH group controls OH group controls regiochemistryregiochemistry
OOHH CHCH33
OOHH
CHCH33
NNOO22
Dr. Wolf's CHM 201 & 202 22 - 39
HalogenationHalogenation
NitrationNitration
NitrosationNitrosation
SulfonationSulfonation
Friedel-Crafts AlkylationFriedel-Crafts Alkylation
Friedel-Crafts AcylationFriedel-Crafts Acylation
Electrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in Phenols
Dr. Wolf's CHM 201 & 202 22 - 40
NitrosationNitrosationNitrosationNitrosation
NaNONaNO22
HH22SOSO44, H, H22OO
0°C0°C
OOHH
NNOO
(99%)(99%)only strongly activated only strongly activated rings undergo nitrosation rings undergo nitrosation when treated with nitrous when treated with nitrous acidacid
OOHH
Dr. Wolf's CHM 201 & 202 22 - 41
HalogenationHalogenation
NitrationNitration
NitrosationNitrosation
SulfonationSulfonation
Friedel-Crafts AlkylationFriedel-Crafts Alkylation
Friedel-Crafts AcylationFriedel-Crafts Acylation
Electrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in Phenols
Dr. Wolf's CHM 201 & 202 22 - 42
OOHH
CHCH33HH33CC
SOSO33HH
(69%)(69%)
HH22SOSO44
100°C100°C
SulfonationSulfonationSulfonationSulfonation
OOHH
CHCH33HH33CC
OH group controls OH group controls regiochemistryregiochemistry
Dr. Wolf's CHM 201 & 202 22 - 43
HalogenationHalogenation
NitrationNitration
NitrosationNitrosation
SulfonationSulfonation
Friedel-Crafts AlkylationFriedel-Crafts Alkylation
Friedel-Crafts AcylationFriedel-Crafts Acylation
Electrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in Phenols
Dr. Wolf's CHM 201 & 202 22 - 44
Friedel-Crafts AlkylationFriedel-Crafts AlkylationFriedel-Crafts AlkylationFriedel-Crafts Alkylation
(63%)(63%)
(CH(CH33))33COH reacts COH reacts
with Hwith H33POPO44 to give to give
(CH(CH33))33CC++
OOHH
CC
CHCH33
CHCH33HH33CC
CHCH33
HH33POPO44
60°C60°C
(CH(CH33))33COHCOH
OOHH
CHCH33
Dr. Wolf's CHM 201 & 202 22 - 45
HalogenationHalogenation
NitrationNitration
NitrosationNitrosation
SulfonationSulfonation
Friedel-Crafts AlkylationFriedel-Crafts Alkylation
Friedel-Crafts AcylationFriedel-Crafts Acylation
Electrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in PhenolsElectrophilic Aromatic Substitution in Phenols
Dr. Wolf's CHM 201 & 202 22 - 46
Acylation of PhenolsAcylation of PhenolsAcylation of PhenolsAcylation of Phenols
Acylation can take place either on the ringAcylation can take place either on the ringby electrophilic aromatic substitution or onby electrophilic aromatic substitution or onoxygen by nucleophilic acyl substitutionoxygen by nucleophilic acyl substitution
Dr. Wolf's CHM 201 & 202 22 - 47
Friedel-Crafts AcylationFriedel-Crafts AcylationFriedel-Crafts AcylationFriedel-Crafts Acylation
AlClAlCl33
OOHH
(74%)(74%)
CHCH33CClCCl
OO OOHH CC
OO CHCH33
++ ortho isomerortho isomer
(16%)(16%)
under Friedel-Crafts under Friedel-Crafts conditions, acylation conditions, acylation of the ring occursof the ring occurs(C-acylation)(C-acylation)
Dr. Wolf's CHM 201 & 202 22 - 48
O-AcylationO-AcylationO-AcylationO-Acylation
(95%)(95%)
in the absence of AlClin the absence of AlCl33, acylation of the , acylation of the
hydroxyl group occurs (O-acylation)hydroxyl group occurs (O-acylation)
OOHH
CHCH33(CH(CH22))66CClCCl
OO
++
OOC(CHC(CH22))66CHCH33 OO
Dr. Wolf's CHM 201 & 202 22 - 49
O- versus C-AcylationO- versus C-AcylationO- versus C-AcylationO- versus C-Acylation
OOC(CHC(CH22))66CHCH33 OO
OOHH CC
OO (CH(CH22))66CHCH33
AlClAlCl33
formed fasterformed faster more stablemore stableO-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 22 - 50
Carboxylation of PhenolsCarboxylation of PhenolsCarboxylation of PhenolsCarboxylation of Phenols
Aspirin and Aspirin and the the
Kolbe-Schmitt Kolbe-Schmitt ReactionReaction COHCOH
OO
OCCHOCCH33
OO
Dr. Wolf's CHM 201 & 202 22 - 51
how is salicylic acid prepared?how is salicylic acid prepared?
Aspirin is prepared from salicylic acidAspirin is prepared from salicylic acidAspirin is prepared from salicylic acidAspirin is prepared from salicylic acid
COHCOH
OO
OOCCHCCH33
OO HH22SOSO44
COHCOH
OO
OOHHOO
CHCH33COCCHCOCCH33
OO
Dr. Wolf's CHM 201 & 202 22 - 52
called the Kolbe-Schmitt reactioncalled the Kolbe-Schmitt reaction
acidification converts the sodium salt shownacidification converts the sodium salt shownabove to salicylic acidabove to salicylic acid
Preparation of Salicylic AcidPreparation of Salicylic AcidPreparation of Salicylic AcidPreparation of Salicylic Acid
COCO22
125°C, 100 atm125°C, 100 atm
CONaCONa
OO
OHOHONaONa
Dr. Wolf's CHM 201 & 202 22 - 53
acid-base considerations provide an explanation:acid-base considerations provide an explanation:stronger base on left; weaker base on rightstronger base on left; weaker base on right
What Drives the Reaction?What Drives the Reaction?What Drives the Reaction?What Drives the Reaction?
++ COCO22
OO ––
••••••••••••
stronger base:stronger base:ppKKaa of conjugate of conjugate acid = 10acid = 10
weaker base:weaker base:ppKKaa of conjugate of conjugate acid = 3acid = 3
OO
––
••••••••••••CC
OO
OO
••••
••••HH
•••• ••••
Dr. Wolf's CHM 201 & 202 22 - 54
how does carbon-carbon bond form?how does carbon-carbon bond form?
recall electron delocalization in phenoxide ionrecall electron delocalization in phenoxide ion
negative charge shared by oxygen and by thenegative charge shared by oxygen and by thering carbons that are ortho and para to oxygenring carbons that are ortho and para to oxygen
Preparation of Salicylic AcidPreparation of Salicylic AcidPreparation of Salicylic AcidPreparation of Salicylic Acid
COCO22
125°C, 100 atm125°C, 100 atm
CONaCONa
OO
OHOHONaONa
Dr. Wolf's CHM 201 & 202 22 - 55
••••OO••••
HH
HH
HH
HH
HH
••••–– ••••OO
••••
HH
HH
HH
HH
HH
––•••• ••••OO
••••
HH
HH
HH
HH
HH––••••
••••OO••••
HH
HH
HH
HH
HH
––••••
Dr. Wolf's CHM 201 & 202 22 - 56
OO
CC
Mechanism of ortho CarboxylationMechanism of ortho CarboxylationMechanism of ortho CarboxylationMechanism of ortho Carboxylation
••••
••••
••••
•••• OO OO
HH
••••••••••••––
OO•••• ••••
HH
––
••••••••••••
CCOO
OO•••• ••••
Dr. Wolf's CHM 201 & 202 22 - 57
OO
CC
Mechanism of ortho CarboxylationMechanism of ortho CarboxylationMechanism of ortho CarboxylationMechanism of ortho Carboxylation
••••
••••OO
••••
•••• OO
HH
••••••••••••
––
OO•••• ••••
HH
––
••••••••••••
CCOO
OO•••• •••• OO
––
••••••••••••CC
OO
OO
••••
••••HH
•••• ••••
Dr. Wolf's CHM 201 & 202 22 - 58
Why ortho?Why ortho?
Why not para? Why not para?
Why ortho?Why ortho?
Why not para? Why not para? OO••••••••••••
–– OO
––
••••••••••••CC
OO
OO
••••
••••HH
•••• ••••
OO••••
••••HH
CC
•••• ••••OO
OO••••••••••••––
Dr. Wolf's CHM 201 & 202 22 - 59
weaker base:pKa of conjugate acid = 3
Why ortho?Why ortho?
Why not para? Why not para?
Why ortho?Why ortho?
Why not para? Why not para? OO••••••••••••
–– OO
––
••••••••••••CC
OO
OO
••••
••••HH
•••• ••••
stronger base:pKa of conjugate acid = 4.5
OO••••
••••HH
CC
•••• ••••OO
OO••••••••••••––
Dr. Wolf's CHM 201 & 202 22 - 60
Hydrogen bonding between carboxylate and hydroxylHydrogen bonding between carboxylate and hydroxylgroup stabilizes salicylate ion. Salicylate is less basic group stabilizes salicylate ion. Salicylate is less basic than para isomer and predominates under conditionsthan para isomer and predominates under conditionsof thermodynamic control.of thermodynamic control.
Intramolecular Hydrogen BondingIntramolecular Hydrogen Bonding
in Salicylate Ionin Salicylate Ion
Intramolecular Hydrogen BondingIntramolecular Hydrogen Bonding
in Salicylate Ionin Salicylate Ion
OO
OO
CC OO ––
HH
Dr. Wolf's CHM 201 & 202 22 - 61
Preparation of Aryl EthersPreparation of Aryl EthersPreparation of Aryl EthersPreparation of Aryl Ethers
Dr. Wolf's CHM 201 & 202 22 - 62
Typical Preparation is by Williamson SynthesisTypical Preparation is by Williamson SynthesisTypical Preparation is by Williamson SynthesisTypical Preparation is by Williamson Synthesis OONaNa ++ RRXX
OORR NaNaXX++
SSNN22
Dr. Wolf's CHM 201 & 202 22 - 63
Typical Preparation is by Williamson SynthesisTypical Preparation is by Williamson SynthesisTypical Preparation is by Williamson SynthesisTypical Preparation is by Williamson Synthesis OONaNa ++ RRXX
OORR NaNaXX++
SSNN22
but the other combinationbut the other combination XX ++ RROONaNa
fails because aryl halides are normally unreactivefails because aryl halides are normally unreactivetoward nucleophilic substitutiontoward nucleophilic substitution
Dr. Wolf's CHM 201 & 202 22 - 64
acetoneacetone
heatheat
ExampleExampleExampleExample OONaNa ++ CHCH33II
OOCHCH33
(95%)(95%)
Dr. Wolf's CHM 201 & 202 22 - 65
acetone, heatacetone, heat
ExampleExampleExampleExample OOHH ++
(86%)(86%)
HH22CC CHCHCHCH22BrBr
KK22COCO33 OOCHCH22CHCH CHCH22
Dr. Wolf's CHM 201 & 202 22 - 66
Aryl Ethers from Aryl HalidesAryl Ethers from Aryl HalidesAryl Ethers from Aryl HalidesAryl Ethers from Aryl Halides FFNONO22
++ KKOOCHCH33
CHCH33OHOH
25°C25°C
OOCHCH33
NONO22
++ KKFF
(93%)(93%)
nucleophilic aromatic substitution is effective nucleophilic aromatic substitution is effective with nitro-substituted (ortho and/or para) aryl with nitro-substituted (ortho and/or para) aryl halides halides
Dr. Wolf's CHM 201 & 202 22 - 67
Cleavage of Aryl EthersCleavage of Aryl Ethersby Hydrogen Halidesby Hydrogen Halides
Cleavage of Aryl EthersCleavage of Aryl Ethersby Hydrogen Halidesby Hydrogen Halides
Dr. Wolf's CHM 201 & 202 22 - 68
Cleavage of Cleavage of AlkylAlkyl ArylAryl Ethers EthersCleavage of Cleavage of AlkylAlkyl ArylAryl Ethers Ethers
OO
ArAr
RR
HH++ ••••OO
ArAr
RR
•••••••• HH BrBr
••••••••
••••
••••••••
••••BrBr••••
––++ ++
Dr. Wolf's CHM 201 & 202 22 - 69
Cleavage of Cleavage of AlkylAlkyl ArylAryl Ethers EthersCleavage of Cleavage of AlkylAlkyl ArylAryl Ethers Ethers
OO
ArAr
RR
HH++ ••••OO
ArAr
RR
•••••••• HH BrBr
••••••••
••••
••••••••
••••BrBr••••
––++ ++
RR BrBr••••
••••••••
++ OO
ArAr••••
HH••••
An An alkylalkyl halide is halide is formed; never an formed; never an arylaryl halide! halide!
Dr. Wolf's CHM 201 & 202 22 - 70
++
ExampleExampleExampleExample OOCHCH33
OHOH
OHOH
OHOH
(85-87%)(85-87%)
CHCH33BrBr
(57-72%)(57-72%)
HBrHBr
heatheat
Dr. Wolf's CHM 201 & 202 22 - 71
Claisen RearrangementClaisen Rearrangement
of Allyl Aryl Ethersof Allyl Aryl Ethers
Claisen RearrangementClaisen Rearrangement
of Allyl Aryl Ethersof Allyl Aryl Ethers
Dr. Wolf's CHM 201 & 202 22 - 72
Allyl Aryl Ethers Rearrange on HeatingAllyl Aryl Ethers Rearrange on HeatingAllyl Aryl Ethers Rearrange on HeatingAllyl Aryl Ethers Rearrange on Heating
OHOH
CHCH22CHCH CHCH22
OCHOCH22CHCH CHCH22
200°C200°C
(73%)(73%)
allyl group allyl group migrates to migrates to ortho positionortho position
Dr. Wolf's CHM 201 & 202 22 - 73
rewrite as rewrite as
MechanismMechanismMechanismMechanism OCHOCH22CHCH CHCH22
OO OO
HH
keto-to-enolketo-to-enol
isomerizationisomerization
OHOH
Dr. Wolf's CHM 201 & 202 22 - 74
Claisen rearrangement is an example of a Claisen rearrangement is an example of a sigmatropic rearrangement. A sigmatropic rearrangement. A bond migrates bond migratesfrom one end of a conjugated from one end of a conjugated electron system electron systemto the other.to the other.
this this bond breaks bond breaks
this this bond forms bond forms
““conjugated conjugated electron system” electron system” is the allyl groupis the allyl group
Sigmatropic RearrangementSigmatropic RearrangementSigmatropic RearrangementSigmatropic Rearrangement OO
OO
HH
Dr. Wolf's CHM 201 & 202 22 - 75
Oxidation of Phenols:Oxidation of Phenols:QuinonesQuinones
Oxidation of Phenols:Oxidation of Phenols:QuinonesQuinones
Dr. Wolf's CHM 201 & 202 22 - 76
The most common examples of phenol oxidationsThe most common examples of phenol oxidationsare the oxidations of 1,2- and 1,4-benzenediolsare the oxidations of 1,2- and 1,4-benzenediolsto give quinones. to give quinones.
(76-81%)(76-81%)
QuinonesQuinonesQuinonesQuinones OHOH
OHOH
OO
OO
NaNa22CrCr22OO7,7, H H22SOSO44
HH22OO
Dr. Wolf's CHM 201 & 202 22 - 77
The most common examples of phenol oxidationsThe most common examples of phenol oxidationsare the oxidations of 1,2- and 1,4-benzenediolsare the oxidations of 1,2- and 1,4-benzenediolsto give quinones. to give quinones.
(68%)(68%)
QuinonesQuinonesQuinonesQuinones
OO
OOAgAg22OO
diethyl etherdiethyl ether
OHOH
OHOH
CHCH33
CHCH33
Dr. Wolf's CHM 201 & 202 22 - 78
AlizarinAlizarin(red pigment)(red pigment)
Some quinones are dyesSome quinones are dyesSome quinones are dyesSome quinones are dyes OO
OO
OHOH
OHOH
Dr. Wolf's CHM 201 & 202 22 - 79
Ubiquinone (Coenzyme Q)Ubiquinone (Coenzyme Q)nn = 6-10 = 6-10
involved in biological electron transportinvolved in biological electron transport
Some quinones are important biomoleculesSome quinones are important biomoleculesSome quinones are important biomoleculesSome quinones are important biomolecules
CHCH33OO
CHCH33OO
OO
OO
CHCH33
nn
Dr. Wolf's CHM 201 & 202 22 - 80
Vitamin KVitamin K(blood-clotting factor)(blood-clotting factor)
Some quinones are important biomoleculesSome quinones are important biomoleculesSome quinones are important biomoleculesSome quinones are important biomolecules OO
CHCH33
OO CHCH33 CHCH33 CHCH33 CHCH33
CHCH33
Dr. Wolf's CHM 201 & 202 22 - 81
Spectroscopic Analysis of PhenolsSpectroscopic Analysis of Phenols
Dr. Wolf's CHM 201 & 202 22 - 82
infrared spectra of phenols combine features infrared spectra of phenols combine features of alcohols and aromatic compoundsof alcohols and aromatic compounds
O—H stretch analogous to alcohols nearO—H stretch analogous to alcohols near3600 cm3600 cm-1-1
C—O stretch at 1200-1250 cmC—O stretch at 1200-1250 cm-1-1
Infrared SpectroscopyInfrared SpectroscopyInfrared SpectroscopyInfrared Spectroscopy
Dr. Wolf's CHM 201 & 202 22 - 83
2000200035003500 30003000 25002500 1000100015001500 500500
Wave number, cmWave number, cm-1-1
Figure 24.3: Infrared Spectrum of p-CresolFigure 24.3: Infrared Spectrum of p-Cresol
O—HO—H
C—HC—H
C—OC—O
CHCH33
OHOH
Dr. Wolf's CHM 201 & 202 22 - 84
Hydroxyl proton of OH group lies between alcoholsHydroxyl proton of OH group lies between alcoholsand carboxylic acids; range is and carboxylic acids; range is ca. ca. 4-12 ppm 4-12 ppm(depends on concentration). For (depends on concentration). For pp-cresol the OH-cresol the OHproton appears at proton appears at 5.1 ppm (Figure 24.4). 5.1 ppm (Figure 24.4).
1H NMR1H NMR CHCH33HOHO
HH HH
HHHH
Dr. Wolf's CHM 201 & 202 22 - 85
01.02.03.04.05.06.07.08.09.010.0
Chemical shift (Chemical shift (, ppm), ppm)
CCHH33HHOO
HH HH
HHHH
Dr. Wolf's CHM 201 & 202 22 - 86
CHCH33
OHOH
139.8139.8
21.321.3129.4129.4
112..3112..3 116.1116.1
155.1155.1
121.7121.7
Oxygen of hydroxyl group deshields carbonOxygen of hydroxyl group deshields carbonto which it is directly attached.to which it is directly attached.
The most shielded carbons of the ring are those thatThe most shielded carbons of the ring are those thatare ortho and para to the oxygen.are ortho and para to the oxygen.
13C NMR13C NMR
Dr. Wolf's CHM 201 & 202 22 - 87
maxmax
204 nm204 nm
256 nm256 nm
maxmax
210 nm210 nm
270 nm270 nm
maxmax
235 nm235 nm
287 nm287 nm
Oxygen substitution on ring shifts Oxygen substitution on ring shifts maxmax to longer to longer
wavelength; effect is greater in phenoxide ion.wavelength; effect is greater in phenoxide ion.
UV-VISUV-VIS OHOH
OO––
Dr. Wolf's CHM 201 & 202 22 - 88
Prominent peak for molecular ion. Most intense Prominent peak for molecular ion. Most intense peak in phenol is for molecular ion.peak in phenol is for molecular ion.
m/z m/z 9494
Mass SpectrometryMass Spectrometry OHOH••++
••••
Dr. Wolf's CHM 201 & 202 22 - 89
End of Chapter 22