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REACTIONS OF BENZENEREACTIONS OF BENZENE
AND ITS DERIVATIVEAND ITS DERIVATIVE
REACTIONS OF BENZENEREACTIONS OF BENZENE
AND ITS DERIVATIVEAND ITS DERIVATIVEGroup 5:Group 5:L Th Dim Quyn
Vin Hng Nhung
o Ngc ThiNguyn Anh Quc
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OutlinesIntrodution
Electrophilic Aromatic Substitution
Disubstitution and Polysubstitution
Nucleophilic Aromatic Substitution
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Introdution to benzene
function groups
The Halogen
The Nitro group (-NO2)The Sulfonic acid group (-SO3H)
The Alkyl group (-R)
The Acyl group (RCO-)
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Electrophilic Aromatic Substitution
The characteristic reaction of benzene is electrophilic aromaticsubstitutiona hydrogen atom is replaced by an electrophile (E+)
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All occur by a common three-step mechanism
Step 1: Generation of the electrophile
Step 2: Reaction of the electrophile with the ring
Step 3: Proton transfer to regenerate the aromatic ring
+
H
EE+
Hslow
Resonance-stabilized cation intermed iate
E
H
E
H
E
H E
Basefast Base-H
Mechanism
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Benzenedoesnotundergoadditionreactionslikeotherunsaturatedhydrocarbons,becauseaddition would
yieldaproductthatisnotaromatic. Substitutionofahydrogenkeepsthearomaticring
intact.
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Chlorination and Bromination
+-
A molecula complex with
a positive cha ge on chlorineand a negative charge on iron
Ferric chlorid e
(a Lewis acid)
Chlorine
(a Lewis base)
+Cl
FeCl
Cl Fe
Cl Cl+
An ion pair containing
a chloroniu m ion
-Cl Fe
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Step 1: Formationofachloroniumion(E+)
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Step 2: Reactionofthechloroniumion withthearomaticring
+
+
+
Resonance-stabil i ed cation intermediate
+
slow, ratedeterm ining
Cl
HH
Cl
H
Cl
Cl +
Step 3: Protontransferto FeCl4- forms HCl,regeneratesthe Lewisacidcatalyst,andgiveschlorobenzene
Cl
H
Cl Cl
Cl
Cl
Fe
Cl H-Cl Fe Cl
Cl
Cl
Chlorobenzene
f a st
Catio nintermed iate
++
+
+-
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Nitration and Sulfonation
Nitrationandsulfonationintroducetwodifferentfunctionalgroupsintothearomaticring.
Nitrationisespeciallyusefulbecausethenitrogroupcanbe
reducedtoan NH2 group.
Nitration
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The electrophile is NO2+, generated in this way
H O NO2 O SO3 HH O NO2H
H
HSO4++ +
Nit ic cidConjugat acidof
nitic
acid
O
H
H NO2 H O
H
NO2++
+
The n it onium
ion
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COOH
NO2
3H2
Ni
COOH
NH2
2H2O
4-Aminobenzoic acid4-Nitrobenzoic acid
+(3 atm)
+
A particular value of nitration is that the nitro group can bereduced to a 1 amino group.
Reduction occurs with other reagents such as an active metal(Fe, Sn or Zn) in HCl.
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Carried out using concentrated sulfuric acidcontaining dissolved sulfur trioxide.
Concentrated sulfuric acid containing dissolved sulfurtrioxide is fuming sulfuric acid.
+ SO3
H2SO4
SO3H
Benzene Benzenesulfonic acid
Sulfonation
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Friedel-CraftsAlkylation
Friedel-Crafts alkylation forms a new C-C bond between anaromatic ring and an alkyl group.
Mixing benzene and alkyl halide, AlCl3 catalyst, form alkylbenzene and HX
ClAlCl3
HCl+
Benzene 2-Chloropropane
(Isopropyl chloride)
Cumene
(Isopropylbenzene)
+
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Step 1: Formation of an alkyl cation as an ion pair.
Step 2: Attack of the alkyl cation on the ring.
Step 3: Proton transfer regenerates aromaticity.
+ R+
R
H
R
H
R
H
A resonance-stabilized cation
+
+
+
H
RCl lCl3 R AlCl3 HCl
R Cl ClAl
Cl
ClR Cl
Cl
Cl
Al Cl R
+
AlCl4-
An ion pair containinga carbocation
+-
+
A molecularcomplex
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Friedel-CraftsAcylation ofBenzene
Friedel-Crafts acylation forms a new C-C bondbetween a benzene ring and an acyl group.
OCl
CH3CCl
O
AlCl3
AlCl3
O
O
HCl
HCl+
Benzene AcetophenoneAcetylchloride
4-Phenylbutanoylchloride
E-Tetralone
+
+
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The electrophile is an acylium ion.
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A special value of Friedel-Crafts acylations is
preparation of unrearranged alkylbenzenes.
+A lCl3
N 2 H 4 , KOH
diethyle eglyc l Is utyl e ze e2-Methyl-1-
phe yl-1-p p e
2-Methylp p ylchl ide
Cl
O
O
Wolff-Kishner reduction
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OtherElectrophilicAromaticAlkylations
Carbocations are also generated from alkenes andalcohols by treatment of an alkene with a protic
acid, most commonly H2SO4, H3PO4, or HF/BF3
CH3CH=CH2H3PO4
Benzene P ene ene
+
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By treating an alkene with a Lewis acid,
By treating an alcohol with H2SO4 or H3PO4.
+
AlCl3
Benzene Cyclohexene Phenylcyclohexane
Benzene
HOH2
H3PO4
++
2-Methyl-2-propanol(tert-Butyl al ohol)
2-Methyl-2-phenylpropane(tert-Butylbenzene)
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Di- and Polysubstitution Two c aracteristics ofa s stit e t
Orientation: Certain substituents direct preferentially to ortho & para
positions; others to meta positions. Substituents are classified as eitherorthoortho--parapara directingdirecting
ormeta directingmeta directing toward furthersubstitution.
Rate: Certain substituents causetherate ofa second
substitution to be greaterthan thatforbenzene itself;others causetherateto belower. Substituents are classified as activatingactivating ordeactivatingdeactivating
toward furthersubstitution.
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-OCH3 is ortho-para directing.
-COOH is meta directing.
O H3
HNO3H3 OOH
O H3
NO2
O H3
NO2
H2 O
p-Nitroa iso e (55%)
o-Nitroa iso e (44%)
iso e
+++
C H
HN H2S
4
N 2
C H C H
N 2N 2
C H
100C
m-N it o-b oi
a i80%)
B n oia i
+ ++
o-N it o-b oi
a i18%)
p-N it o-b o i
a i2%)
Di- and Polysubstitution
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Weakly
activating
Ortho-
araDirecting
Weaklydeactivating
Moderatelyactivating
Stronglyactivating NH NHR NR OH
NH R NH r
OR
OCArOCR
R
F Cl Br I
: : : : :
::
: ::
:
:
:
:
:
:
:
:
:
:
:
::::
Stronglydeactivating
Moderatelydeactivating
CH
O O
CR COH
SO H
CORO
CNH
NO NH+
CF CClMetaDirectin
g
C N
O O O O
OO
Table 1.1. Directing effects of substitution on futher substitution
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DiDi-- and Polysubstitutionand Polysubstitution
Generalizations:Directivity: Alkyl, phenyl,and all substituents in which
theatom bonded to thering has an unshared pairof
electrons are ortho-para directing. All othersubstituentsare meta directing.
Activation: All ortho-para directing groups exceptthe
halogens areactivating toward furthersubstitution. Thehalogens are weakly deactivating.
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DiDi-- and Polysubstitution.and Polysubstitution.
The orderofsteps is important.
CH
3
K2 Cr2 O7
H2 O4
HNO3
H2 O4
CH3
NO2
COOH
H2 O4
HNO3
K2 Cr2O7
H2 O4
COOH
NO2
COOH
NO2
m-N itrobenzoicacid
p-N itrobenzoicacid
Note the key point: transformation of o,p director into m
director.
o,p
m
o,p
m
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Theory of Directing Effects
The rate of EAS is limited by the slowest stepin the reaction
For almost every EAS, the rate-determining
step is attack of E+
on the aromatic ring to givea resonance-stabilized cation intermediate
The more stable this cation intermediate, thefaster the rate-determining step and the faster
the overall reaction
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Theory of Directing EffectsTheory of Directing Effects
-OCH3 is directing: assume ortho-para attack.Here only para attack is shown.
O H3
NO +
fa t
+
( ) ( ) (f)
O H3
H N O
O H3
H NO
O H3
H NO
O H3
H NO
O H3
N O
H+
+
lo
+
+
+
(g)
::::
: : :
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Theory of Directing Effects
-OCH3: assume ortho-para attack
O H3
NO +
fa t
+
( ) ( ) (f)
O H3
H N O
O H3
H NO
O H3
H NO
O H3
H NO
O H3
N O
H+
+
lo
+
+
+
(g)
::::
: : :
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Theory of Directing EffectsTheory of Directing Effects
-CO2H is directing; assume meta attack.
COO
O+
COO
O
COO
O
COO
O
-+
COO
O
+ slow
fast
(a) ( ) (c)
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Theory of Directing EffectsTheory of Directing Effects
-CO2H is directing: assume ortho-para attack.COOH
NO2+
COOH
H NO2
COOH
H NO2
COOH
H NO2
-H+
COOH
NO2
+ slow
fast
(d) (e) (f)
Themostdisfa oredcontribu tin structure
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Activating-Deactivating
Any resonance effectAny resonance effect, such as that of -NH2, -OH,and -OR, that delocalizes the positive charge onthe cation intermediate lowers the activation
energy for its formation, and has an activatingeffect toward further EAS
Any resonance or inductive effectAny resonance or inductive effect, such as that of-NO2, -CN, -CO, or -SO3H, that decreases
electron density on the ring deactivates the ringtoward further EAS
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Aryl halides, dont undergo substitution by either of the
SN1 or SN2 pathways that are characteristic of nucleophilic
aliphatic substitution
Undergo nucleophilic aromatic substitution under certain
condition but by mechanisms quite different from those for
nucleophilic aliphatic substitution
Nucleophilic aromatic substitutions are far less common
than electrophilic aromatic substitutions
Nucleophilic Aromatic Substitution
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Benzyne IntermediatesBenzyne Intermediates
When heated at 3000C under hight pressure with aqueous
NaOH, chlorobenzene is converted to sodium phenoxide.
Neutralization of this salt with aqueous Acid gives phenol
Cl
2 NaOHH2O
O-
Na
NaCl H2O
So i me o i e
C loro -be ze e
++re ss re, 300oC
+
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3-M e thy lphe n ol(m-Cre so l)
2-M eth ylp he no l(o-Cre so l)
+
CHCl OH
CH CH
OH
1 . NaOH,he at ,p ressure
. HCl, H O
BenzyneBenzyne IntermediatesIntermediates
At pressure high and temperature atAt pressure high and temperature at 50050000CC reactionreaction
appears to involveappears to involve nucleophilicnucleophilic substitution of group OH forsubstitution of group OH for
groupgroup ClCl on the benzene ringon the benzene ring
For example oFor example o--chlorotoluenechlorotoluene under these conditionsunder these conditions
gives a mixture of ogives a mixture of o--cresol and mcresol and m--cresolcresol
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Benzyne IntermediatesBenzyne Intermediates
The same type of reaction can be brought about usingof sodiumamide in liquid ammonia
Under these condition p-chlorotoluene gives amixture
of 4-methylaniline and 3-methylaniline
CH3
Cl
NaNH2NH3 (l)
CH3
NH2
CH3
NH2
NaCl
3-Met yla ili e(m-Tol i i e)
4-Met yla ili e(p-Tol i i e)
++(-33
oC)
+
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BenzyneBenzyne IntermediatesIntermediates
Mechainsm
Step1: Dehydrohalogenation of the benzene ring gives a
benzyne intermediate
When elimination of HX gives a benzyne intermediate, thatthen adds the nucleophile to give new products
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Step 2: Addition to either carbon of the triple is possible
Step 3: Proton transfer from ammonia to the carbanion
BenzyneBenzyne IntermediatesIntermediates
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AdditionAddition-- eliminationelimination
When an aryl halide contains electron-
withdrawing NO2 groups ortho and/or para to X,
nucleophilic aromatic substitution takes placereadily
Aromatic halides are normally inert to the
types of nucleophiles that readily displace
halide ions from alkyl halides
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AdditionAddition-- eliminationelimination
When 1-chloro-2,4-dinitrobenzene is heated at reflux in aqueous Na2CO3
Hence product react with acid
form 2,4-dinitrophenol
ClNO 2
NO 2
N a2 CO 3 , H 2 O
O-
Na+
NO 2
NO 2
1 0 0oC
S o i m 2 ,4 -d i i tro -e o id e
1 -C loro -2 ,4 -d i i tro b e z e e
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Mechainsm
AdditionAddition-- eliminationelimination
Step 1: the nucleophile adds to the aromatic ring at the carbon
bearing the halogen
Step 2:Elimination of halide ion regenerates the aromatic ring and
gives the observed product
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2,6-di-tert-butyl-4-methylphenol
Or Butylated
hydroxytoluene (BHT)In food industry, it is anantioxidation in food toretard spoilage
ProblemsProblems
Problem 22.23: Mechanism
OH
2,6-di-tert-butyl-4-methylphenol
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Starting materials :
4-methylphenol (p-cresol)2-methylpropene
H3PO4 catalystOH
p-cresol2-methylpropene
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Summary
Reaction sof
Benzene
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Summary
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References
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Thank for your
attention