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Chapter 12Chapter 12
Substituted benzenesSubstituted benzenes
The Benzene Ring as a SubstituentThe Benzene Ring as a Substituent
••CCCC
CC ••CC
benzylic carbon is analogous to allylic carbonbenzylic carbon is analogous to allylic carbon
Resonance in Benzyl RadicalResonance in Benzyl Radical
HH HH••
HH
HHHH
HH
HH
unpaired electron is delocalized betweenunpaired electron is delocalized between
benzylic carbon and the ring carbons that arebenzylic carbon and the ring carbons that are
ortho and para to itortho and para to it
Resonance in Benzyl RadicalResonance in Benzyl Radical
HH HH
HH
HHHH
HH••
HH
unpaired electron is delocalized betweenunpaired electron is delocalized between
benzylic carbon and the ring carbons that arebenzylic carbon and the ring carbons that are
ortho and para to itortho and para to it
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Resonance in Benzyl RadicalResonance in Benzyl Radical
HH HH
HH
HHHH
HH
••
HH
unpaired electron is delocalized betweenunpaired electron is delocalized between
benzylic carbon and the ring carbons that arebenzylic carbon and the ring carbons that are
ortho and para to itortho and para to it
Resonance in Benzyl RadicalResonance in Benzyl Radical
HH HH
HH
HHHH
HH••
HH
unpaired electron is delocalized betweenunpaired electron is delocalized between
benzylic carbon and the ring carbons that arebenzylic carbon and the ring carbons that are
ortho and para to itortho and para to it
industrial processindustrial process
FreeFree--radical chlorination of tolueneradical chlorination of toluene
highly regioselective for benzylic positionhighly regioselective for benzylic position
CHCH33
ClCl22CHCH22ClCl
or or
heatheat
TolueneToluene Benzyl chlorideBenzyl chloride
Similarly, dichlorination and trichlorination areSimilarly, dichlorination and trichlorination are
FreeFree--radical chlorination of tolueneradical chlorination of toluene
..chlorination gives:chlorination gives:
CClCCl33
CHClCHCl22
(Dichloromethyl)benzene(Dichloromethyl)benzene (Trichloromethyl)benzene(Trichloromethyl)benzene
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is used in the laboratory to introduce ais used in the laboratory to introduce a
halogen at the benzylic positionhalogen at the benzylic position
Benzylic BrominationBenzylic Bromination
CHCH33
+ Br + Br 22
CClCCl44, 80, 80°°CC
lightlight
+ HBr + HBr
CHCH22Br Br
NONO22 NONO22
pp--NitrotolueneNitrotoluene pp--NitrobenzylNitrobenzyl
bromide (71%)bromide (71%)
is a convenient reagent for benzylic brominationis a convenient reagent for benzylic bromination
NN--Bromosuccinimide (NBS)Bromosuccinimide (NBS)
CClCCl44
benzo lbenzo l
CHCH22CHCH33
++NNBr Br
OO CHCHCHCH33
NHNH
OO
++
peroxide,peroxide,
heatheatOO OO
(87%)(87%)
Oxidation ofOxidation of Alkylbenzenes Alkylbenzenes
Site of Oxidation is Benzylic CarbonSite of Oxidation is Benzylic Carbon
CHCH
CHCH22RR
or or
COHCOH
OONaNa22Cr Cr 22OO77
HH22SOSO44
HH22OO
CHRCHR22
or or
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ExampleExample
OO
NaNa22Cr Cr 22OO77
HH22SOSO44
HH22OO
heatheat
33
NONO22
pp--NitrotolueneNitrotoluene
NONO22
pp--NitrobenzoicNitrobenzoic
acid (82acid (82--86%)86%)
ExampleExample
CH(CHCH(CH33))22 COHCOH
OO
HH22SOSO44
HH22OO
heatheat
CHCH33 COHCOH
(45%)(45%)
OO
Nucleophilic SubstitutionNucleophilic Substitution
inin BenzylicBenzylic HalidesHalides
Primary Benzylic HalidesPrimary Benzylic Halides
CHCH22ClClOO22NN
acetic acidacetic acid
NaOCCHNaOCCH33
OOMechanism is SMechanism is S
NN
22
CHCH22OCCHOCCH33OO22NN
OO
(78(78--82%)82%)
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What about SWhat about SNN1?1?
Relative solvolysis rates in aqueous acetoneRelative solvolysis rates in aqueous acetone
CC
33
CHCH33
ClCl CC
33
CHCH33
ClClCHCH33
tertiary benzylic carbocation is formedtertiary benzylic carbocation is formed
more rapidly than tertiary carbocation;more rapidly than tertiary carbocation;
therefore, more stabletherefore, more stable
What about SWhat about SNN1?1?
Relative rates of formation:Relative rates of formation:
CC CCCHCH33
33
CHCH33
++
33
CHCH33
++
more s a emore s a e less stableless stable
Compare.Compare.
++CCCC
CC ++CC
benzylic carbon is analogous to allylic carbonbenzylic carbon is analogous to allylic carbon
Resonance in Benzyl CationResonance in Benzyl Cation
HH HH++
HH
HHHH
HH
HH
unpaired electron is delocalized betweenunpaired electron is delocalized between
benzylic carbon and the ring carbons that arebenzylic carbon and the ring carbons that are
ortho and para to itortho and para to it
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Resonance in Benzyl CationResonance in Benzyl Cation
HH HH
HH
HHHH
HH++
HH
unpaired electron is delocalized betweenunpaired electron is delocalized between
benzylic carbon and the ring carbons that arebenzylic carbon and the ring carbons that are
ortho and para to itortho and para to it
Resonance in Benzyl CationResonance in Benzyl Cation
HH HH
HH
HHHH
HH
++
HH
unpaired electron is delocalized betweenunpaired electron is delocalized between
benzylic carbon and the ring carbons that arebenzylic carbon and the ring carbons that are
ortho and para to itortho and para to it
Resonance in Benzyl CationResonance in Benzyl Cation
HH HH
HH
HHHH
HH++
HH
unpaired electron is delocalized betweenunpaired electron is delocalized between
benzylic carbon and the ring carbons that arebenzylic carbon and the ring carbons that are
ortho and para to itortho and para to it
SolvolysisSolvolysis
CC
CHCH33
ClCl
CHCH33
CHCH33CHCH22OHOH
CC
CHCH33
CHCH33
OCHOCH22CHCH33
(87%)(87%)
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PhenolsPhenolsNomenclatureNomenclature
NomenclatureNomenclature
OHOH
named on basis of phenol as parentnamed on basis of phenol as parent
55--ChloroChloro--22--methylmethylphenolphenol
33
ClCl
substituents listed in alphabetical order substituents listed in alphabetical order
lowest numerical sequence: first point of lowest numerical sequence: first point of
difference ruledifference rule
NomenclatureNomenclature
OHOH OHOHOHOH
OHOH
OHOH
1,21,2--BenzenediolBenzenediol 1,31,3--BenzenediolBenzenediol 1,41,4--BenzenediolBenzenediol
(common name:(common name:
pyrocatechol)pyrocatechol)
(common name:(common name:
resorcinol)resorcinol)
(common name:(common name:
hydroquinone)hydroquinone)
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NomenclatureNomenclature
OHOH
pp--Hydroxybenzoic acidHydroxybenzoic acid
COCO22
HH
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 outrank
hydroxylhydroxyl groupgroup
The OH group of phenols allows hydrogen bondingThe OH group of phenols allows hydrogen bonding
Physical PropertiesPhysical Properties
to other phenol molecules and to water.to other phenol molecules and to water.
HH OOOO
Hydrogen Bonding in PhenolsHydrogen Bonding in Phenols Physical PropertiesPhysical Properties
Compared to compounds of similar size andCompared to compounds of similar size and
molecular weight, hydrogen bonding in phenolmolecular weight, hydrogen bonding in phenol
raises its melting point, boiling point, andraises its melting point, boiling point, andsolubility in water.solubility in water.
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Physical PropertiesPhysical Properties
CC66HH55CHCH33 CC66HH55OHOH CC66HH55FF
Molecular weightMolecular weight 9292 9494 9696
– –9595 4343 – –4141Melting point (Melting point (°°C)C)
BoilingBoiling
point (point (°°C,1 atm)C,1 atm)
111111 132132 8585
Solubility inSolubility in
HH22O (g/100 mL,25O (g/100 mL,25°°C)C)
0.050.05 8.28.2 0.20.2
Acidity of Phenols Acidity of Phenols
most characteristic property ofmost characteristic property ofphenols is their acidityphenols is their acidity
CompareCompare
••••••
••••••
•• – –
••
KKaa = 10= 10--1010
++HH ++
•• ••
CHCH33CHCH22OO HH••••
••••
aa == --
++HH ++ CHCH33CHCH22OO
••••
••••
– – ••••
Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion
•••• OO
••••
HH HH
••••
– – •••• OO
••••
HH HH – – ••••
HH HH
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Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion
•••• OO
••••
HH HH – – ••••
•••• OO
••••
HH HH
••••
HHHH
Delocalized negative charge in phenoxide ionDelocalized negative charge in phenoxide ion
•••• OO
••••
HH HH – – ••••
•••• OO
••••
HH HH
••••
HHHH
Phenols are converted to phenoxide ionsPhenols are converted to phenoxide ions
in aqueous basein aqueous base
OO HH••••
••••OO••
••••••
••••
– –
++ HOHO – –
++ HH22OO
stronger acidstronger acid weaker acidweaker acid
Substituent EffectsSubstituent Effects
on theon the
Acidity of Phenols Acidity of Phenols
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ElectronElectron--releasing groups have little or no effectreleasing groups have little or no effect
OHOHOHOH OHOH
CHCH33 OCHOCH33
KKaa:: 1 x 101 x 10--1010 5 x 105 x 10--1111 6 x 106 x 10--1111
ElectronElectron--withdrawing groups increase aciditywithdrawing groups increase acidity
OHOHOHOH OHOH
ClCl NONO22
KKaa:: 1 x 101 x 10--1010 4 x 104 x 10--99 7 x 107 x 10--88
Effect of electronEffect of electron--withdrawing groups is mostwithdrawing groups is most
pronounced at ortho and para positionspronounced at ortho and para positions
OHOHOHOH
NONO22
OHOH
NONO
NONO22
KKaa:: 6 x 106 x 10--88 4 x 104 x 10--99 7 x 107 x 10--88
Effect of strong electronEffect of strong electron--withdrawing groupswithdrawing groups
is cumulativeis cumulative
OHOH OHOH
NONO22
OHOH
NONO22OO22NN
NONO22 NONO22NONO22
KKaa:: 7 x 107 x 10--88 1 x 101 x 10--44 4 x 104 x 10--11
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Resonance DepictionResonance Depiction
••••••
•••••••• – –
••••
HH
HH
HH
HH
••••
HH
HH
HH
HH
••
NN••••OO OO
••••
•••••••••••• – –
++••••
– –
NN••••OO OO
••••
•••••••••••• – –
++
Preparation of Aryl EthersPreparation of Aryl Ethers
Typical Preparation is by Williamson SynthesisTypical Preparation is by Williamson Synthesis
SS 22OONaNa ++ RRXX OORR NaNaXX++
Typical Preparation is by Williamson SynthesisTypical Preparation is by Williamson Synthesis
SS 22OONaNa ++ RRXX OORR NaNaXX++
but the other combinationbut the other combination
++ aa
fails because aryl halides are normally unreactivefails because aryl halides are normally unreactive
toward nucleophilic substitutiontoward nucleophilic substitution
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ExampleExample
heatheatOONaNa ++ CHCH33II OOCHCH33
(95%)(95%)
Carboxylation of PhenolsCarboxylation of Phenols
Aspirin and Aspirin and
thethe
KolbeKolbe--SchmittSchmitt
OCCHOCCH33
OO
eac oneac on COHCOH
OO
Aspirin is prepared from salicylic acid Aspirin is prepared from salicylic acid
By esterificationBy esterification
OO
COHCOH
OOCCHCCH33
HH22SOSO44COHCOH
OOHHCHCH33COCCHCOCCH33
how is salicylic acid prepared?how is salicylic acid prepared?
Preparation of Salicylic AcidPreparation of Salicylic Acid
OHOHONaONa
125125°°C, 100 atmC, 100 atm CONaCONa
OO
--
acidification converts the sodium salt shownacidification converts the sodium salt shown
above to salicylic acidabove to salicylic acid
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acidacid--base considerations provide an explanation:base considerations provide an explanation:
What Drives the Reaction?What Drives the Reaction?
++ COCO22
OO – –
••••
•••••••• OO
– – ••••••••CC OO
••••
••••HH
stronger base:stronger base:ppKKaa of conjugateof conjugateacid = 10acid = 10
weaker base:weaker base:ppKKaa of conjugateof conjugateacid = 3acid = 3
••••
OO•••• ••
••
Preparation of Salicylic AcidPreparation of Salicylic Acid
OHOHONaONa
how does carbonhow does carbon--carbon bond form?carbon bond form?
125125°°C, 100 atmC, 100 atm CONaCONa
OO
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 the
ring carbons that are ortho and para to oxygenring carbons that are ortho and para to oxygen
•••• OO
••••
HH HH
••••
– – •••• OO
••••
HH HH – – ••••
HH HH
•••• OO
•••• ••
•• OO••••
HH
HH
HH
HH
HH – – ••••
HH
HH
HH
HH
HH
– – ••••
Mechanism ofMechanism of orthoortho CarboxylationCarboxylation
••••••••OO
•••• – –
OO••••
••••
OO
HH
••••
••••OO••
••
HH
– –
••••
••••••••
CC
OO
OO•••• ••••
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Mechanism ofMechanism of orthoortho CarboxylationCarboxylation
••••OO••••
•••• – –
OO••••
••••
OO
HH
••••
••••OO••
••
HH
– –
••••
••••••••
CC
OO
OO•••• ••
••
••••
– –
••••
••••••••CC
OO
OO
••••
•••• ••
••
Reimer Reimer--Tiemann reaction.Tiemann reaction.
Synthesis of phenolic aldehydesSynthesis of phenolic aldehydes
DichlorocarbenesDichlorocarbenes
Reimer Reimer--Tiemann rxnTiemann rxn
OH O- O- OH
CHCl3, aq. NaOH
70 C
CHCl2 CHO
HCl
CHO
Mechanism of Reimer Mechanism of Reimer--TiemannTiemann
OH- + CHCl3 H2O + Cl3C:- Cl- + Cl2C:
O- O-
CCl2
O-
CHCl2
+ :CCl2 H
Strong ElectrophileStrong Electrophile
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Oxidation of Phenols:Oxidation of Phenols:
QuinonesQuinones
The most common examples of phenol oxidationsThe most common examples of phenol oxidationsare the oxidations of 1,2are the oxidations of 1,2-- and 1,4and 1,4--benzenediolsbenzenediols
QuinonesQuinones
to give quinones.to give quinones.
OHOH OO
NaNa22Cr Cr 22OO7,7, HH22SOSO44
(76(76--81%)81%)
OHOH OO
HH22OO
The most common examples of phenol oxidationsThe most common examples of phenol oxidationsare the oxidations of 1,2are the oxidations of 1,2-- and 1,4and 1,4--benzenediolsbenzenediols
QuinonesQuinones
to give quinones.to give quinones.
OO
OO Ag Ag22OO
OHOH
OHOH
(68%)(68%)
diethyl ether diethyl ether
CHCH33 CHCH33
Some quinones are dyesSome quinones are dyes
OHOH
Alizarin Alizarin(red pigment)(red pigment)
OO
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Some quinones are important biomoleculesSome quinones are important biomolecules
OO
CHCH33OO
CHCH33OO
OO
CHCH33
nn
Ubiquinone (Coenzyme Q)Ubiquinone (Coenzyme Q)nn = 6= 6--1010
involved in biological electron transportinvolved in biological electron transport
Some quinones are important biomoleculesSome quinones are important biomolecules
OO
CHCH33
OOCHCH
33CHCH
33CHCH
33CHCH
33
CHCH33
Vitamin KVitamin K(blood(blood--clotting factor)clotting factor)
Aryl Diazonium Salts Aryl Diazonium Salts
Nitrosation of Primary ArylaminesNitrosation of Primary Arylamines
gives aryl diazonium ionsgives aryl diazonium ions
aryl diazonium ions are much more stable thanaryl diazonium ions are much more stable than
alkyl diazonium ionsalkyl diazonium ions
most aryl diazonium ions are stable under themost aryl diazonium ions are stable under theconditions of their formation (0conditions of their formation (0--1010°°C)C)
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Nitrosation of Primary ArylaminesNitrosation of Primary Arylamines
gives aryl diazonium ionsgives aryl diazonium ions
aryl diazonium ions are much more stable thanaryl diazonium ions are much more stable than
alkyl diazonium ionsalkyl diazonium ions
most aryl diazonium ions are stable under themost aryl diazonium ions are stable under the
conditions of their formation (0conditions of their formation (0--1010°°C)C)
ArN ArN NN++
RNRN NN++ fastfast
slowslow
RR++ ++ NN22
Ar Ar ++ ++ NN22
Example:Example:
33 22 22
NaNONaNO22, H, H22SOSO44
HH22O, 0O, 0--55°°CC
(CH(CH33))22CHCH NN NN++
HSOHSO44 – –
Synthetic Origin of Aryl Diazonium SaltsSynthetic Origin of Aryl Diazonium Salts
Ar Ar HH
Ar Ar NNOO22
Ar Ar NNHH22
33,, 22 44
Fe, HCl or Pd, HFe, HCl or Pd, H22
Ar Ar NN NN++
NaNONaNO22, HCl, H, HCl, H22OO
00--55°°CC
Synthetic Transformations of Aryl Diazonium SaltsSynthetic Transformations of Aryl Diazonium Salts
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Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
Ar Ar Br Br Ar Ar ClCl
Ar Ar NN NN++
Ar Ar FF Ar Ar CNCN
Ar Ar HH
Ar Ar OHOH
Ar Ar II
Preparation of PhenolsPreparation of Phenols
hydrolysis of a diazonium salthydrolysis of a diazonium salt
Ar Ar NN NN++
Ar Ar OHOH
22 ,,
ExampleExample
(CH(CH33))22CHCH NNHH22
2. H2. H22O, heatO, heat
1. NaNO1. NaNO22, H, H22SOSO44
HH22O, 0O, 0--55°°CC
(CH(CH33))22CHCH OOHH
(73%)(73%)
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
Ar Ar Br Br Ar Ar ClCl
Ar Ar NN NN
++
Ar Ar FF Ar Ar CNCN
Ar Ar HH
Ar Ar OHOH
Ar Ar II
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Preparation of Aryl IodidesPreparation of Aryl Iodides
reaction of an aryl diazonium salt withreaction of an aryl diazonium salt with
Ar Ar NN NN++
po ass um o epo ass um o e
KIKI
Ar Ar II
ExampleExample
2. KI, room temp.2. KI, room temp.
1. NaNO1. NaNO22, HCl, HCl
HH22O, 0O, 0--55°°CC
22
Br Br Br Br
--
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
Ar Ar Br Br Ar Ar ClCl
Ar Ar NN NN
++
Ar Ar FF Ar Ar CNCN
Ar Ar HH
Ar Ar OHOH
Ar Ar II
Preparation of Aryl FluoridesPreparation of Aryl Fluorides
Ar Ar NN NN
++
Ar Ar FF
heat the tetrafluoroborate salt of a diazonium ion;heat the tetrafluoroborate salt of a diazonium ion;
process is called the Schiemann reactionprocess is called the Schiemann reaction
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ExampleExample
22
CCHCCH22CHCH33
2. HBF2. HBF44
. a. a 22, ,, ,
HH22O, 0O, 0--55°°CC
CCHCCH22CHCH33
(68%)(68%)
OO..
OO
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
Ar Ar Br Br Ar Ar ClCl
Ar Ar NN NN++
Ar Ar FF Ar Ar CNCN
Ar Ar HH
Ar Ar OHOH
Ar Ar II
Preparation of Aryl Chlorides and BromidesPreparation of Aryl Chlorides and Bromides
Ar Ar Br Br Ar Ar ClCl
Ar Ar NN NN
++
heating a diazonium salt with copper(I) chloride orheating a diazonium salt with copper(I) chloride or
bromidebromide
substitutions of diazonium salts that use copper(I)substitutions of diazonium salts that use copper(I)
halides are calledhalides are called Sandmeyer Sandmeyer reactionsreactions
ExampleExample
22
NONO22
2. CuCl, heat2. CuCl, heat
. a. a 22, ,, ,
HH22O, 0O, 0--55°°CC
NONO22
(68(68--71%)71%)
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ExampleExample
2. CuBr, heat2. CuBr, heat
. a. a 22, r,, r,
HH22O, 0O, 0--1010°°CCNNHH22
ClCl
Br Br
ClCl
(89(89--95%)95%)
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
Ar Ar Br Br Ar Ar ClCl
Ar Ar NN NN++
Ar Ar FF Ar Ar CNCN
Ar Ar HH
Ar Ar OHOH
Ar Ar II
Preparation of Aryl NitrilesPreparation of Aryl Nitriles
Ar Ar NN NN
++
Ar Ar CNCN
salt with copper(I) cyanidesalt with copper(I) cyanide
this is another type of Sandmeyer reactionthis is another type of Sandmeyer reaction
ExampleExample
2. CuCN, heat2. CuCN, heat
. a. a 22, ,, ,
HH22O, 0O, 0°°CCNNHH22
CHCH33
CNCN
CHCH33
(64(64--70%)70%)
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Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
Ar Ar Br Br Ar Ar ClCl
Ar Ar NN NN++
Ar Ar FF Ar Ar CNCN
Ar Ar HH
Ar Ar OHOH
Ar Ar II
Transformations of Aryl Diazonium SaltsTransformations of Aryl Diazonium Salts
hypophosphorous acid (Hhypophosphorous acid (H33POPO22) reduces diazonium) reduces diazonium
Ar Ar NN NN++
this is calledthis is called reductive deaminationreductive deamination
Ar Ar HH
ExampleExample
aa 22,, 22 44,,
HH33POPO22
NNHH22
CHCH33 CHCH33
(70(70--75%)75%)
Value of Diazonium SaltsValue of Diazonium Salts
1)1) allows introduction of substituents such asallows introduction of substituents such as
, , ,, , ,
2)2) allows preparation of otherwise difficultlyallows preparation of otherwise difficultly
accessible substitution patternsaccessible substitution patterns
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NNHH22
ExampleExample
NaNONaNO22, H, H22SOSO44,,
NNHH22
Br Br
HH22O, CHO, CH33CHCH22OHOHBr Br 22
HH22OO
Br Br Br Br
(74(74--77%)77%)
(100%)(100%)
Br Br
Azo Azo CouplingCoupling
Azo Coupling Azo Coupling
Diazonium salts are weak electrophiles.Diazonium salts are weak electrophiles.
eac w s rong y ac va e aroma ceac w s rong y ac va e aroma c
compounds by electrophilic aromaticcompounds by electrophilic aromatic
substitution.substitution.
Azo Coupling Azo Coupling
Diazonium salts are weakDiazonium salts are weak electrophileselectrophiles..
eac w s rong y ac va e aroma ceac w s rong y ac va e aroma c
compounds bycompounds by electrophilicelectrophilic aromaticaromatic
substitution.substitution.
Ar Ar NN NN++
Ar' Ar' HH++ Ar Ar NN NN Ar' Ar'
an azo compoundan azo compound
Ar' Ar' must bear a strongly electronmust bear a strongly electron--releasing groupreleasing group
such as OH, OR, or NRsuch as OH, OR, or NR22..
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http://slidepdf.com/reader/full/benzene-sub 25/25
ExampleExample
OHOH
++++ CC66HH55NN NN ClCl – –
OHOH
NN NCNC66HH55
HalobenzenesHalobenzenes and Nucleophilicand Nucleophilic
Aromatic Substitution Aromatic Substitution
ClCl OHOHNaOH, 350CNaOH, 350C
300 atm.300 atm.
Reactivity increases as we attach more electronReactivity increases as we attach more electron
withdrawing groups:withdrawing groups:
NaOH, 160CNaOH, 160C
300 atm.300 atm.ClClOO22NN OHOHOO22NN
NONO22NONO22
HH22O, warmO, warmClCl
OO22NN
NONO22
OHOHOO22NN
NONO22
Mechanism:
If the ring is substituted by an electron withdrawing group the
reaction proceeds through a two-step carbanion intermediate.
O2N Cl O2N
Cl
O2N OH
Slow Fast
OH-
OH
If the ring is unsubstituted, the reaction proceeds through a
benzyne intermediate.
Cl NH2Slow
NH2-, NH3-HCl