1 substitution reactions of benzene and its derivatives: electrophilic addition/elimination...
TRANSCRIPT
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Substitution Reactions of Benzene and Its Derivatives:Electrophilic Addition/Elimination Reactions.
Benzene is aromatic: a cyclic conjugated compound with 6 electrons
Reactions of benzene lead to the retention of the aromatic core
Electrophilic aromatic substitution replaces a proton on benzene with another electrophile
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Aromatic Substitutions
via the Wheland Intermediates All electrophile additions involve a cationic intermediate that
was first proposed by G. W. Wheland of the University of Chicago and is often called the Wheland intermediate.
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Bromination of Aromatic Rings
Benzene’s electrons participate as a Lewis base in reactions with Lewis acids
The product is formed by loss of a proton, which is replaced by bromine
FeBr3 is added as a catalyst to polarize the bromine reagent
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Addition Intermediate in Bromination
The addition of bromine occurs in two steps In the first step the electrons act as a nucleophile toward
Br2 (in a complex with FeBr3) This forms a cationic addition intermediate from benzene
and a bromine cation The intermediate is not aromatic and therefore high in
energy
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Formation of the Product from the Intermediate
The cationic addition intermediate transfers a proton to FeBr4
- (from Br- and FeBr3)
This restores aromaticity (in contrast with addition in alkenes)
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Aromatic Chlorination and Iodination
Chlorine and iodine (but not fluorine, which is too reactive) can produce aromatic substitution with the addition of other reagents to promote the reaction
Chlorination requires FeCl3
Iodine must be oxidized to form a more powerful I+ species (with Cu+ or peroxide)
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Aromatic Nitration and Sulfonation
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Aromatic Nitration and Sulfonation
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Alkylation of Aromatic Rings:The Friedel–Crafts Reaction
Aromatic substitution of a R+ for H
Aluminum chloride promotes the formation of the carbocation
Only alkyl halides can be used (F, Cl, I, Br)
Aryl halides and vinylic halides do not react (their carbocations are too hard to form)
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CH3CH2Br
AlBr3
+ HBr AlBr3+
CH3CH2 Br + AlBr3 CH3CH2 Br AlBr3
δ δ
CH3CH2 Br AlBr3δ δ
H
CH2CH3
+ AlBr4
1.
2.
Alkylation of Aromatic Rings:The Friedel–Crafts Reaction
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Multiple alkylations can occur because the first alkylation is activating
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Carbocation Rearrangements During Alkylation
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Carbocation Rearrangements During Alkylation
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Acylation of Aromatic Rings Reaction of an acid chloride (RCOCl) and an
aromatic ring in the presence of AlCl3 introduces acyl group, COR
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Mechanism of Friedel-Crafts Acylation
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Reduction of Aryl Alkyl Ketones Allows Synthesis
of Non-rearranged Alkyl Benzenes. Aromatic ring activates neighboring carbonyl group toward
reduction. Ketone is converted into an alkylbenzene by catalytic
hydrogenation over Pd catalyst, or Wolff-Kishner or Clemensen reductions.
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Reduction of Aryl Alkyl Ketones Allows Synthesis
of Non-rearranged Alkyl Benzenes. C
CH3
CH3
CH3
+ C
CH3H3C
H3CC
Cl
O
AlCl3
C
C
CH3
CH3
CH3
O
Zn/Hg + HCl
C
CH3
CH3
CH3
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Nucleophile Reaction Conditions Reaction mode(Purpose)
N2H4and derivatives
1. N2H4 / H3O+
2. OH- / DMSOIntermolecular 1,2-addition(Wolff-Kishner reduction of
aldehydes, ketones;synthesis of hydrazones, alkanes
and alkyl benzenes)
H2
H2 / (Me/C)Me = Pd, Pt, Ni
Intermolecular 1,2-addition(reduction of aldehydes,
ketones and esters;synthesis of alcohols
and alkanes)
H2
Zn/Hg amalgamin HCl
Clemensen Reduction(reduction of aryl ketones toalkyl aromatic compounds)
Summary of reduction nucleophiles in 1,2-additionsto aromatic C=O groups.
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Substituent Effects in Aromatic Rings Substituents can cause a compound to be (much) more or (much)
less reactive than benzene and affect the orientation of the reaction.
There substituents are: ortho- and para-directing activators, ortho- and para-directing deactivators, and meta-directing deactivators.
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Summary Table:Effect of Substituents in Aromatic Substitution
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The Explanation of Substituent Effects Activating groups donate electrons to the ring, stabilizing the Wheland intermediate (carbocation).
Deactivating groups withdraw electrons from the ring, destabilizing the Wheland intermediate.
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Origins of Substituent Effects: Inductive Effects
The overall effect of a substituent is defined by the interplay of inductive effects and resonance effects.
Inductive effect - withdrawal or donation of electrons through bonds. Controlled by electronegativity and the polarity of bonds in functional groups,
i.e. halogens, C=O, CN, and NO2 withdraw electrons through bond connected to ring.
Alkyl group inductive effect is to donate electrons.
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Origins of Substituent Effects: Resonance Effects
Resonance effect - withdrawal or donation of electrons through a bond due to the overlap of a p orbital on the substituent with a p orbital on the aromatic ring.
C=O, CN, and NO2 substituents withdraw electrons from the aromatic ring by resonance, i.e. the electrons flow from the rings to the substituents.
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Origins of Substituent Effects: Resonance Effects
Resonance effect - withdrawal or donation of electrons through a bond due to the overlap of a p orbital on the substituent with a p orbital on the aromatic ring.
Halogen, OH, alkoxyl (OR), and amino substituents donate electrons, i.e. the electrons flow from the substituents to the ring.
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NH2
Br Br
Br
C N C
N
OH
O
HOH
Br Br
Br
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Ortho- and Para-Directing
Activators: Alkyl Groups
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Ortho- and Para-Directing Activators:
OH and NH2
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Ortho- and Para-Directing
Deactivators: Halogens
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Meta-Directing Deactivators Inductive and resonance effects reinforce each other. Ortho and para intermediates destabilized by deactivation of
the carbocation intermediate
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Disubstituted Benzenes:
Additivity of Effects If the directing effects of the two groups are the same, the
result is additive.
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Disubstituted Benzenes:
Opposition of Effects If the directing effects of the two groups are different, the more powerful
activating group decides the principal outcome. Usually the mixture of products results.
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Linked Benzenes:
Opposition of Effects
NH
O
NH
OCH3Br / AlBr3
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Diazonium Salts: The Sandmeyer Reaction
Primary arylamines react with HNO2, yielding stable arenediazonium salts.
The N2 group can be replaced by a nucleophile.
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Reactions of Arenediazonium Salts Allow Formation of “Impossibly” Substituted Aromatic
Rings.
Typical synthetid sequence consists of: (1) nitration, (2) reduction, (3) diazotization, and (4) nucleophilic
substitution
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Preparation of Aryl Halides
Reaction of an arenediazonium salt with CuCl or CuBr gives aryl halides (Sandmeyer Reaction).
Aryl iodides form from reaction with NaI without a copper(I) salt.
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Br2 / AlBr3
+N2Cl-
Br
?
X
NOO
Fe / HCl
BF4NO2
NOO
Br
NH2
Br
KNO2 / HCl HBr/ CuCN
Br
X = Br, I , F
Br
Br
NaI HBF4I
Br
F
Br
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Preparation of Aryl Nitriles and Carboxylic Acids
An arenediazonium salt and CuCN yield the nitrile, ArCN, which can be hydrolyzed to ArCOOH.
OHO
CH3Br / AlBr3
OHO
KMnO4
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CH3Br / AlBr3
OHO
OHO
?
NOO
Fe / HCl
BF4NO2
NOO
H2N
KNO2 / HCl KCN / CuCN H3O+
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Reduction to a CH aromatic bond
By treatment of a diazonium salt with hypophosphorous acid, H3PO2
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Br
Br Br
Br
Br Br
X
N2 Cl
Br
KNO2
HCl, 0°C
NH2
Br
Br2
0°C/H2O
NH2
FeHCl
NO2
H3PO2
0°C or RT
Reduction via diazonium salts
BrBrBrBr
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OH
fromphenol
CO2H
OH
OH
CO2H
CO2CH3
OH
CO2CH3
NO2 BF4
CO2CH3
NO2
NaOH CO2
Fe
HCl
CO2CH3
NH2
HCl, 0°CKNO2
CO2CH3
N2 Cl
H3O+
CO2CH3
OH
metameta
v.s.
Preparation of complex phenols