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Transcript
Chapter 16
Introduction
• Electrophilic aromatic substitution is the most
common reaction of aromatic compounds
– It replaces a proton (H+) on an aromatic ring with
another electrophile (E+)
– It leads to the retention of the aromatic core
Some electrophilic aromatic substitution reactions
1.
Bromination of Aromatic Rings
• Benzene is a site of electron density
– Its 6  electrons are in a cyclic conjugated system
– Its 6  electrons are sterically accessible to other
reactants because they are located above or below
the plane
• Benzene acts as an electron donor (a Lewis
base or nucleophile)
– It reacts with electron acceptors (Lewis acids or
electrophiles)
– Benzene’s  electrons participate as a Lewis
base in reactions with Lewis acids
•
Bromination of benzene occurs in two steps:
–
Step 1: The  electrons act as a nucleophile toward
Br2 (in a complex with FeBr3) to form a nonaromatic
carbocation intermediate
–
Step 2: The resonance-stabilized carbocation
intermediate loses H+ to regenerate the aromatic ring
Electrophilic Alkene Addition
Electrophilic Aromatic Bromination
•
Aromatic rings are less reactive toward electrophiles
than alkenes
– Unlike alkenes, benzene does not react rapidly with
Br2 in CH2Cl2
– For bromination, benzene requires FeBr3 as a
catalyst to polarize the bromine reagent and make it
more electrophilic
• Step 1: The  electrons act as a nucleophile and
attack the polarized Br2 (in a complex with FeBr3)
to form a nonaromatic carbocation intermediate
– It is a slow, rate-limiting step (high DG‡)
– The carbocation is doubly allylic (nonaromatic)
and has three resonance forms
– The carbocation intermediate is not aromatic and
is high in energy (less stable than benzene)
– Step 1 is endergonic, has a high DG‡ and is a slow
reaction
• Step 2: The resonance-stabilized carbocation
intermediate loses H+ to regenerate the aromatic
ring and yield a substitution product in which H+
is replaced by Br+
– It is similar to the 2nd step of an E1 reaction
– The carbocation intermediate transfers a H+ to
FeBr4- (from Br- and FeBr3)
– This restores aromaticity (in contrast with
addition in alkenes)
– Step 2 is exergonic, has a low DG‡ and is a fast
reaction
Electrophilic Aromatic Bromination: Mechanism
Why is there electrophilic aromatic substitution rather
than addition?
– Substitution reaction retains the stability of the
aromatic ring and is exergonic
Addition
Loss of aromaticity
Endergonic
Substitution
Retention of aromaticity
Exergonic
Practice Problem: Monobromination of toluene gives a mixture of
three bromotoluene products. Draw and name
them.
2.
Other Aromatic Substitutions
• The reaction with bromine involves a mechanism
that is similar to many other reactions of benzene
with electrophiles
– The cationic intermediate was first proposed by
G. W. Wheland and is often called the Wheland
intermediate
Electrophilic Aromatic Substitution
•
An electrophilic aromatic substitution reaction
involves two steps:
– reaction of an electrophile E+ with an aromatic ring
– loss of H+ from the resonance-stabilized carbocation
intermediate to regenerate the aromatic ring
• The same general mechanism is used by
other aromatic substitutions including:
 Chlorination
 Iodination
 Nitration
 Sulfonation
F is too reactive for monofluorination
Aromatic Chlorination
•
Benzene ring reacts with Cl2 in the presence of FeCl3
catalyst to yield chlorobenzene
– It requires FeCl3 to polarize Cl2 (make it more
electrophilic)
Aromatic Iodination
•
Benzene ring reacts with I2 in the presence of an
oxidizing agent (H2O2 or CuCl2) to yield iodobenzene
– Iodine must be oxidized to form a more powerful
electrophilic I+ species (with Cu2+ or peroxide)
Aromatic Nitration
•
Benzene ring reacts with a mixture of concentrated
nitric and sulfuric acids (HNO3 and H2SO4) to yield
nitrobenzene
– The combination of nitric acid and sulfuric acid
produces NO2+ (nitronium ion), an electrophile
– The electrophile NO2+ is produced when HNO3 is
protonated by H2SO4 and loses H2O
– NO2+ reacts with benzene to give a carbocation
intermediate which loses H+ to yield nitrobenzene
– Aromatic nitration is useful in the pharmaceutical
industry because the nitro-substituted product can
be reduced by Fe or SnCl2 to yield arylamine
Aromatic Sulfonation
•
Benzene ring reacts with fuming sulfuric acid (a
mixture of H2SO4 and SO3) to yield benzenesulfonic
acid
– The reactive electrophile is either HSO3+ or neutral
SO3 depending on reaction conditions
– The reactive electrophile is either sulfur trioxide SO3
or its conjugate acid HSO3+
– The reaction occurs via the Wheland intermediate
(carbocation)
– The reaction is reversible (Sulfonation is favored in
strong acid; desulfonation, in hot, dilute aqueous
acid)
– Aromatic sulfonic acids are useful as intermediates
in the synthesis of dyes and pharmaceuticals.
•
Example: Sulfadrugs
A sulfadrug
– Aromatic sulfonic acids undergo alkali fusion
reaction
•
Heating with NaOH at 300 ºC followed by neutralization
with acid replaces the SO3H group with an OH
•
Example: Synthesis of p-cresol
Practice Problem: How many products might be formed on
chlorination of o-xylene (o-dimethylbenzene),
m-xylene, and p-xylene?
Practice Problem: When benzene reacts with D2SO4, deuterium
slowly replaces all six hydrogens in the
aromatic ring. Explain.
3.
Alkylation of Aromatic Rings: The
Friedel-Crafts Reaction
• Benzene ring reacts with an alkyl chloride in the
presence of AlCl3 catalyst to yield an arene
– Alkylation was first reported by Charles Friedel
and James Crafts in 1877
• Friedel-Crafts alkylation – is an electrophilic
aromatic substitution in which the electrophile is
a carbocation, R+.
– AlCl3 catalyst promotes the formation of the
alkyl carbocation, R+, from the alkyl halide, RX
– The Wheland (carbocation) intermediate forms
– Alkylation is the attachment of an alkyl group to
benzene; R+ substitutes for H+
Friedel-Crafts Alkylation Reaction: Mechanism
Limitations of the Friedel-Crafts Alkylation
1.
Only alkyl halides can be used (F, Cl, Br, I)
– Aryl halides and vinylic halides do not react (their
carbocations are too high in energy to form)
2.
No reaction occurs if the aromatic ring has an amino
group or a strongly electron-withdrawing group
substituent
– Amino groups react with AlCl3 catalyst in an acidbase reaction
3.
It is difficult to control the reaction. Multiple alkylations
can occur because the first alkylation is activating
– Polyalkylation is often observed
4.
Carbocation rearrangements occur during alkylation,
particularly when a 1o alkyl halide is used
– Catalyst, temperature and solvent affect the amount
of rearrangement
Rearranged
Unrearranged
Carbocation rearrangements of Friedel-Crafts alkylation
– are similar to those that occur during electrophilic
additions to alkenes
– can involve hydride (H:-) or alkyl shifts
More Stable
Limitations of the Friedel-Crafts Alkylation
1.
Only alkyl halides can be used (F, Cl, Br, I)
2.
No reaction occurs if the aromatic ring has an amino
group or a strongly electron-withdrawing group
substituent
3.
It is difficult to control the reaction. Multiple alkylations
can occur because the first alkylation is activating
4.
Carbocation rearrangements occur during alkylation,
particularly when a 1o alkyl halide is used
Practice Problem: The Friedel-Crafts reaction of benzene with 2chloro-3-methylbutane in the presence of AlCl3
occurs with carbocation rearrangement. What
is the structure of the product?
Practice Problem: Which of the following alkyl halides undergo
Friedel-Crafts reaction without
rearrangement?
Explain.
a. CH3CH2Cl
b. CH3CH2CH(Cl)CH3
c. CH3CH2CH2Cl
d. (CH3)3CCH2Cl
e. Chlorocyclohexane
Practice Problem: What is the major monosubstitution product
from Friedel-Crafts reaction of benzene with 1chloro-2-methylpropane in the presence of
AlCl3?
4.
Acylation of Aromatic Rings: The
Friedel-Crafts Reaction
• Benzene ring reacts with a carboxylic acid chloride,
RCOCl, in the presence of AlCl3 catalyst to yield an
acylbenzene
– Acylation is the attachment of an acyl group,-COR,
to benzene; RCO+ substitutes for H+
• Friedel-Crafts acylation – is an electrophilic aromatic
substitution in which the reactive electrophile is a
resonance-stabilized acyl cation, RCO+.
– AlCl3 catalyst promotes the formation of the acyl
cation, RCO+, from the acyl chloride, RCOCl
– The acyl cation, RCO+, does not rearrange; it is
resonance-stabilized
– The Wheland (carbocation) intermediate forms
Friedel-Crafts Acylation Reaction: Mechanism
– The mechanism of Friedel-Crafts acylation is
similar to Friedel-Crafts alkylation
• In Friedel-Crafts acylation, there is no carbocation
rearrangement nor multiple substitution
– No carbocation rearrangement: The acyl cation, RCO+, does not
rearrange because it is resonance-stabilized by interaction of the
vacant orbital on C with lone pair of electrons on O
– No multiple substitution: Acylated benzene is less reactive than
nonacylated benzene
Practice Problem: Identify the carboxylic acid chloride that might
be used in a Friedel-Crafts acylation reaction
to prepare each of the following acylbenzenes
5.
Substituent Effects in Substituted
Aromatic Rings
A substituent present on an aromatic ring affects:
•
the reactivity of the aromatic ring
•
the orientation of the reaction
Substituents affect the reactivity of the aromatic ring
Substituents may
•
activate the ring, make it (much) more reactive than
benzene or
•
deactivate the ring, make it (much) less reactive
than benzene
Substituents affect the orientation of the reaction
Substituents present on the ring determine the
position of the 2nd substitution: ortho, meta, and para
Classification of Substituent Effect
Substituents can be classified as:
•
•
•
ortho- and para-directing activators,
ortho- and para-directing deactivators, and
meta-directing deactivators
The directing effects of the groups correlate with their
reactivities:
•
•
•
All meta-directing groups are strongly deactivating
Most ortho- and para-directing groups are activating
Halogens are unique being ortho- and para-directing but
weakly deactivating
Origins of Substituent Effects
Reactivity and orientation in electrophilic aromatic
substitutions are controlled by an interplay of inductive
effects and resonance effects:
– Inductive effect - withdrawal or donation of electrons
through a s bond
– Resonance effect - withdrawal or donation of
electrons through a  bond
Inductive Effects
Inductive effects - withdrawal or donation of electrons
through a s bond due to electronegativity and polarity
of bonds in functional groups
•
Halogens, C=O, CN, and NO2 groups inductively
withdraw electrons through s bond connected to
ring
•
Alkyl groups inductively donate electrons
•
Halogens, C=O, CN, and NO2 inductively
withdraw electrons through s bond connected to
ring
•
Alkyl groups inductively donate electrons
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, CN, and NO2 groups withdraw electrons
from the aromatic ring by resonance
•
Halogen, OH, alkoxyl (OR), and amino substituents
donate electrons to the aromatic ring by resonance
•
C=O, CN, and NO2 groups withdraw electrons
from the aromatic ring by resonance
–  electrons flow from the ring to the substituents,
placing a positive charge in the ring
•
C=O, CN, and NO2 groups withdraw electrons
from the aromatic ring by resonance placing a
positive charge in the ring
– Effect is greatest at ortho and para
– Z is more electronegative than Y
•
Halogen, OH, alkoxyl (OR), and amino substituents
donate electrons to the aromatic ring by resonance
–  electrons flow from the substituents to the rings
placing a negative charge in the ring
•
Halogen, OH, alkoxyl (OR), and amino substituents
donate electrons to the aromatic ring by resonance
placing a negative charge in the ring
– Effect is greatest at ortho and para
– Y has a lone pair of electrons
Contrasting Effects: Inductive vs Resonance
•
When the two effects act in opposite direction, the
strongest effects dominate.
–
Halogens have electron-withdrawing inductive effects
due to electronegativity
–
Halogens have electron-donating resonance effects due
to lone-pair electrons
–
Resonance interactions are generally weaker, affecting
orientation. Thus, halogens deactivate the ring
Practice Problem: Predict the major product of the monosulfonation
of toluene.
Practice Problem: Write resonance structures for nitrobenzene to
show the electron-withdrawing resonance
effect of the nitro group.
Practice Problem: Write resonance structures for chlorobenzene
to show the electron-donating resonance
effect of the chloro group.
Practice Problem: Predict the major products of the following
reactions
a. Mononitration of bromobenzene
b. Monobromination of nitrobenzene
c. Monochlorination of phenol
d. Monobromination of aniline
6.
An Explanation of Substituent
Effects
• Activating groups donate electrons to the ring,
stabilizing the Wheland intermediate (carbocation)
– OH, OR, NH2 and R
• Deactivating groups withdraw electrons from the
ring, destabilizing the Wheland intermediate
– CN, C=O, NO2 and X
•
An electron-withdrawing group makes the ring more
electron-poor (eg. CN and Cl)
•
An electron-donating group makes the ring more
electron-rich (eg. CH3 and NH2)
Practice Problem: Rank the compounds in each group in order of
their reactivity to electrophilic substitution
a. Nitrobenzene, phenol, toluene, benzene
b. Phenol, benzene, chlorobenzene, benzoic acid
c. Benzene, bromobenzene, benzaldehyde, aniline
Practice Problem: Explain why Friedel-Crafts alkylations often
give polysubstitution but Friedel-Crafts
acylations do not
Practice Problem: Would you expect trifluoromethylbenzene to be
more reactive or less reactive than toluene
toward electrophilic substitution? Explain.
Ortho- and Para-Directing Activators: Alkyl Groups
•
Alkyl groups are activating
– They have an electron-donating inductive effect
•
Alkyl groups are ortho and para directors
– The ortho and para intermediates are the most
stabilized (lower in energy)
– The positive charge is directly on the alkylsubstituted carbon (3o carbon) and is stabilized by
the inductive electron-donating effect of the alkyl
group
•
The positive charge is directly on the alkyl-substituted
carbon (3o carbon) and is stabilized by the inductive
electron-donating effect of the alkyl group
Ortho- and Para-Directing Activators: OH and NH2
•
OH, OR and NH2 groups are activating
– They have a strong electron-donating resonance
and a weak electron-withdrawing inductive effect
•
OH, OR and NH2 groups are ortho and para directors
– The ortho and para intermediates are the most
stabilized (lower in energy)
– The positive charge is stabilized by resonance
donation of an electron pair from O or N
•
The ortho and para intermediates are more stable because
of resonance donation of an electron pair from O or N
Practice Problem: Acetanilide is less reactive than aniline toward
electrophilic substitution. Explain.
Ortho- and Para-Directing Deactivators: Halogens
•
Halogens are deactivating
– They have a strong electron-withdrawing inductive
and a weak electron-donating resonance effect
•
Halogens are ortho and para directors
– The ortho and para intermediates are the most
stabilized (lower in energy)
– Halogens stabilize the positive charge by resonance
donation of a lone pair of electrons
•
The ortho and para intermediates are more stable because
of resonance donation of an electron pair from X
Meta-Directing Deactivators
•
All meta-directing groups are strongly deactivating
– They have electron-withdrawing inductive and
resonance effects that reinforce each other
– The ortho and para intermediates are destabilized
– The positive charge of the carbocation intermediate
in ortho and para attack is directly on the carbon
that bears the deactivating group and resonance
cannot produce stabilization
•
The meta intermediate is more stable because resonance
does not place the positive charge directly on the carbon
that bears the deactivating group
Summary of Substituent Effects in Aromatic Substitution
Practice Problem: Draw resonance structures for the intermediates
from reaction of an electrophile at the ortho, meta,
and para positions of nitrobenzene. Which
intermediates are most stable?
7.
Trisubstituted Benzenes: Additivity
of Effects
Three rules for the additive effects of two different groups:
1. If the directing effects of the two groups are the
same, the result is additive
2. If the directing effects of two groups oppose
each other, the more powerful activating group
determines the principal outcome
3. The position between the two groups in metadisubstituted compounds is unreactive
1.
If the directing effects of the two groups are the
same, the result is additive
–
It gives a single product
2.
If the directing effects of two groups oppose each
other, the more powerful activating group determines
the principal outcome
–
It usually gives mixtures of products
3.
The position between the two groups in metadisubstituted compounds is unreactive
–
The reaction site is too hindered
–
To make aromatic rings with three adjacent
substituents, it is best to start with an orthodisubstituted compound
Practice Problem: What product would you expect from bromination
of p-methylbenzoic acid?
Practice Problem: At what positions would you expect electrophilic
substitution to occur in the following substances?
Practice Problem: Show the major product(s) from reaction of the
following substances with (i) CH3CH2Cl, AlCl3
and (ii) HNO3, H2SO4
8.
Nucleophilic Aromatic Substitution
• Nucleophilic aromatic substitution is a reaction that
aryl halides with electron-withdrawing substituents
undergo
– It replaces a halide ion (X-) on an aromatic ring with
another nucleophile (Nu-)
Nucleophilic Aromatic Substitution
•
A nucleophilic aromatic substitution reaction occurs
in two steps by the addition/elimination mechanism:
– Step 1: Addition of the nucleophile (Nu-) to the
electron-deficient aryl halide, forming a resonance
stabilized carbanion intermediate (Meisenheimer
complex)
– Step 2: Elimination of a halide ion (X-) from the
carbanion intermediate to regenerate the aromatic
ring
Nucleophilic Aromatic Substitution: Mechanism
•
Nucleophilic aromatic substitution occurs ONLY if the
aryl halide has an electron-withdrawing substituent in
ortho and/or para position
– The more such substituents, the faster the reaction
– Only ortho and para electron-withdrawing
substituents can stabilize the anion intermediate
through resonance
•
Only ortho and para intermediate carbanions (Meisenheimer
complex) are resonance stabilized by electron-withdrawal
•
A nucleophilic aromatic substitution reaction is neither
an Sn1 nor an Sn2 reaction:
–
Not Sn1: Aryl cations are unstable for dissociation to occur
–
Not Sn2: Backside displacement is sterically blocked
Electrophilic vs Nucleophilic Aromatic Substitution
• Electrophilic Aromatic
Substitution
• Nucleophilic Aromatic
Substitution
– is favored by electrondonating groups
– is favored by electronwithdrawing groups
– involves a carbocation
intermediate
– involves a carbanion
intermediate
– replaces a H with an
electrophile
– replaces a leaving group
with a nucleophile
• Electron-donating
groups
• Electron-withdrawing
groups
– favor electrophilic
aromatic substitution
– favor nucleophilic
aromatic substitution
– stabilize carbocation
intermediate
– stabilize carbanion
intermediate
– are ortho-para
directors in
electrophilic reaction
– are ortho-para directors
in nucleophilic reaction
but meta-directors in
electrophilic substitution
Practice Problem: Propose a mechanism for the reaction of 1chloroanthraquinone with methoxide ion to give
the substitution product 1-methoxyanthraquinone.
Use curved arrows to show the electron flow in
each step.
9.
Benzyne
• Aryl halides without electron-withdrawing substituents
undergo substitution with a benzyne intermediate
– Phenol is prepared on an industrial scale by
treatment of chlorobenzene with dilute aqueous
NaOH at 340°C under high pressure
•
The synthesis of phenol occurs in two steps by the
elimination/addition mechanism rather than
addition/elimination:
– Step 1: Elimination of a HX from halobenzene in an
E2 reaction catalyzed by a strong base, forming a
highly reactive benzyne intermediate
– Step 2: Addition of a nucleophile (Nu-) to the
benzyne intemediate
Evidence for Benzyne as an Intermediate
• Bromobenzene with 14C only at C1 gives substitution
product with label scrambled between C1 and C2
– The reaction proceeds through a symmetrical
intermediate in which C1 and C2 are equivalent
– The intermediate must be benzyne
• Trapping experiments further demonstrate that
benzyne was the intermediate
– Benzyne is too reactive to be isolated and thus can be
intercepted in a Diels-Alder reaction
Structure of Benzyne
• Benzyne is a highly distorted alkyne
– The triple bond uses sp2-hybridized carbons, not the
usual sp
– The triple bond has one  bond formed by p–p
overlap and one  bond formed by weak sp2–sp2
overlap
Practice Problem: Treatment of p-bromotoluene with NaOH at 300oC
yields a mixture of two products, but treatment of
m-bromotoluene with NaOH yields a mixture of
three products. Explain
10. Oxidation of Aromatic Compounds
There are two reactions of alkylbenzene side chains:
• Oxidation of Alkylbenzene Side Chains
• Bromination of Alkylbenzene Side Chains
Aromatic ring activates neighboring benzylic (C-H)
position toward oxidation
Oxidation of Alkylbenzene Side Chains
•
Alkyl side chains can be oxidized to carboxyl groups,
-CO2H, by strong oxidizing agents such as KMnO4
and Na2Cr2O7
– The alkyl side chains must have a C-H next to the
ring
– This converts an alkylbenzene into a benzoic acid,
Ar-R  Ar-CO2H
•
The mechanism of side-chain oxidation involves
reaction of C-H next to the ring to form intermediate
benzylic radicals
–
t-butylbenzene is inert (no benzylic H’s)
Practice Problem: What aromatic products would you obtain from the
KMnO4 oxidation of the following substances?
Bromination of Alkylbenzene Side Chains
•
Reaction of an alkylbenzene with N-bromo-succinimide
(NBS) and benzoyl peroxide (radical initiator)
introduces Br into the side chain
– Bromination occurs exclusively in the benzylic
position
Mechanism of NBS (Radical) Reaction
•
Abstraction of a benzylic hydrogen atom generates
an intermediate benzylic radical
–
–
–
This reacts with Br2 to yield product and Br·
Br· radical cycles back into reaction to carry on chain
Br2 is produced from reaction of HBr with NBS
•
Bromination occurs exclusively in the benzylic
position because the benzylic radical intermediate is
resonance-stabilized
–
The benzylic radical is stabilized by overlap of its p orbital
with the ring p electron system
Practice Problem: Refer to Table 5.3 for a quantitative idea of the
stability of a benzyl radical. How much stable (in
kJ/mol) is the benzyl radical than a primary alkyl
radical? How does a benzyl radical compare in
stability to an allyl radical
Practice Problem: Styrene, the simplest alkenylbenzene, is prepared
commercially for use in plastics manufacture by
catalytic dehydrogenation of ethylbenzene. How
might you prepare styrene from benzene?
11. Reduction of Aromatic Compounds
There are two reduction reactions:
• Catalytic hydrogenation of Aromatic Rings
• Reduction of Aryl Alkyl Ketones
Catalytic hydrogenation of Aromatic Rings
•
Reduction of an aromatic ring requires more powerful
reducing conditions (H2/Pt at high pressure or
rhodium catalysts)
•
Aromatic rings are inert to catalytic hydrogenation
under conditions that reduce alkene double bonds
–
It is possible to selectively reduce an alkene double
bond in the presence of an aromatic ring
Reduction of Aryl Alkyl Ketones
•
Aromatic ring activates neighboring carbonyl group
toward reduction
•
Aryl alkyl ketone is converted into an alkylbenzene
by catalytic hydrogenation over Pd catalyst
•
Conversion of a carbonyl group to a methylene group
by catalytic hydrogenation (C=O  CH2)
– is limited to aryl alkyl ketones
– is not compatible with the presence of a nitro group
Practice Problem: Show how you would prepare diphenylmethane
(Ph)2CH2, from benzene and an appropriate acid
chloride
12. Synthesis of Trisubstituted Benzenes
•
These syntheses require planning and consideration
of alternative routes
1. Compare the target and the starting material
1. Consider reactions that efficiently produce the
outcome.
1. Look at the product and think of what can lead to
it
•
A synthesis combines a series of proposed steps to
go from a defined set of reactants to a specified
product
Synthesis as a Tool for Learning Organic Chemistry
• In order to propose a synthesis, one must be
familiar with reactions:
–
–
–
–
What they begin with
What they lead to
How they are accomplished
What the limitations are
• The order in which reactions are carried is critical
in the synthesis of substituted aromatic rings
– The introduction of a new substituent is strongly
affected by the directing effects of other substituents
Practice Problem: Synthesize p-bromobenzoic acid from benzene
Br – Bromination using Br2/FeBr3
CO2H – Friedel-Crafts alkylation or acylation followed by oxidation
Practice Problem: Propose a synthesis of 4-chloro-1-nitro-2propylbenzene from benzene
Cl – Chlorination using Cl2/FeCl3
NO2 – Nitration using HNO3/H2SO4
CH2CH2CH3 – Friedel-Crafts acylation followed by reduction
Practice Problem: Propose syntheses of the following substances
from benzene:
a. m-Chloronitrobenzene
b. m-Chloroethylbenzene
c. p-Chloropropylbenzene
Practice Problem: In planning a synthesis, it is important to know
what NOT to do as to know what do. As written,
the following reaction schemes have flaws in
them. What is wrong with each?
Chapter 16