lecture alkene benzen 2
TRANSCRIPT
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Organic ChemistryFor USTH Students
Lecture 2: Electrophilic additionto C=C
Dr. Doan Duy Tien
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Electrophilic addition to C=C
+ General mechanism+ Electrophilic Addition to CarbonCarbon Multiple Bonds
+ Addition of HX
+ Addition of HOH and addition of YX
+ Addition to allene and alkyne+ Substitution at -carbon
+ Reactions via organoborane intermediates
Nucleophilic addition to C=C+ Electron withdrawing group stabilze negative charge
+ Michael reaction with carbon nulceophiles
-1,2 addition favored for more reactive group without steric hindrance
-1,4 addition favored for strerically unhindered 4 position if 2 position is blocked
Contents
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Alkenes are also called olefins.
Alkenes contain a carboncarbon double bond. Terminal alkenes have the double bond at the end of the carbon chain.
Internal alkenes have at least one carbon atom bonded to each end of thedouble bond.
Cycloalkenes contain a double bond in a ring.
Structure and Bonding of C=C
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Structure and Bonding of C=C
Recall that the double bond consists of a bond and a
bond. The
bond is stronger than the bond.
The carbon atom is sp2 hybridized to obtain trigonal planar geometry,with bond angles of approximately 120.
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s + 2 p
=
3 sp2 orbitals
sp2 Hybridization
There is one p orbital left over,and it would be along the z axis.
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H s
Orbital Picture of Ethylene
C
C
H s1
sp2
sp2
sp2
sp2
sp2
sp2
H s
H s
p
x
px
CH
H
CH
H
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Interesting AlkenesEthylene, an industrial starting material for many useful products
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Interesting Alkenes
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The characteristic reaction of alkenes is addition: the bond is broken
and two new bonds are formed.
Addition Reactions
Alkenes have exposed electrons, with the electron density of the bondabove and below the plane of the molecule.
Because alkenes are electron rich, simple alkenes do not react withnucleophiles or bases, reagents that are themselves electron rich. Alkenesreact with electrophiles.
No pi bond
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Because the carbon atoms of a double bond are both trigonalplanar, the elements of X and Y can be added to them from the
same side or from opposite sides.
Addition Reactions
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Five addition reactions of cyclohexene
No pi bond
in products
Addition Reactions
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Two bonds are broken in this reaction: the weak bond of the
alkene and the HX bond, and two new
bonds are formed: one
to H and one to X.
Recall that the HX bond is polarized, with a partial positive
charge on H. Because the electrophilic H end of HX is attracted
to the electron-rich double bond, these reactions are called
electrophilic additions.
Electrophilic Addition ofHydrohalogenation(HX) to C=C
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To draw the products of an addition reaction:
Electrophilic Addition of Hydrohalogenation(HX) to C=C
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The mechanism of electrophilic addition consists of two successive Lewis acid-base reactions. In step 1, the alkene is the Lewis base that donates an electronpair to HBr, the Lewis acid, while in step 2, Br is the Lewis base that donatesan electron pair to the carbocation, the Lewis acid.
Electrophilic Addition of Hydrohalogenation(HX) to C=C: The mechanism
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In the representative energy diagram below, each step has its own energy
barrier with a transition state energy maximum. Since step 1 has a higherenergy transition state, it is rate-determining. H for step 1 is positivebecause more bonds are broken than formed, whereas H for step 2 isnegative because only bond making occurs.
Energy diagram for electrophilic addition:
CH3CH2=CH2 + HBr CH3CH2CH(Br)CH3
Electrophilic Addition of Hydrohalogenation(HX) to C=C: Energy diagram
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With an unsymmetrical alkene, HX can add to the double bond to givetwo constitutional isomers, but only one is actually formed:
This is a specific example of a general trend called Markovnikovs rule.
Markovnikovs rule states that in the addition of HX to an unsymmetricalalkene, the H atom adds to the less substituted carbon atom, that is, thecarbon that has the greater number of H atoms to begin with.
Electrophilic Addition of Hydrohalogenation
(HX) to C=C: Markovnikovs Rule
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The basis of Markovnikovs rule is the formation of a carbocation in therate-determining step of the mechanism.
In the addition of HX to an unsymmetrical alkene, the H atom is added tothe less substituted carbon to form the more stable, more substituted
carbocation.
Electrophilic Addition of Hydrohalogenation
(HX) to C=C: Markovnikovs Rule
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Recall that trigonal planar atoms react with reagents from twodirections with equal probability.
Achiral starting materials yield achiral products.
Sometimes new stereogenic centers are formed fromhydrohalogenation:
A racemic mixture
Electrophilic Addition of Hydrohalogenation(HX) to C=C: Stereochemistry
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The mechanism of hydrohalogenation illustrates why two enantiomers areformed. Initial addition of H+ occurs from either side of the planar doublebond.
Both modes of addition generate the same achiral carbocation. Eitherrepresentation of this carbocation can be used to draw the second step of
the mechanism.
Electrophilic Addition of Hydrohalogenation(HX) to C=C: Stereochemistry
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Hydrohalogenation occurs with syn and anti addition of HX. The terms cis and trans refer to the arrangement of groups in a particular
compound, usually an alkene or disubstituted cycloalkene.
The terms syn and anti describe stereochemistry of a process, for example,how two groups are added to a double bond.
Addition of HX to 1,2-dimethylcyclohexene forms two new stereogeniccenters, resulting in the formation of four stereoisomers (2 pairs ofenantiomers).
Electrophilic Addition of Hydrohalogenation(HX) to C=C: Stereochemistry
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22Reaction of 1,2-dimethyl cyclohexene with HCl
Electrophilic Addition of Hydrohalogenation(HX) to C=C: Stereochemistry
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Electrophilic Addition of Hydrohalogenation(HX) to C=C: Summary
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Electrophilic Addition of Water to C=C
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Electrophilic Addition of Water to C=C
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Alcohols add to alkenes, forming ethers by the same mechanism. For
example, addition of CH3OH to 2-methylpropene, forms tert-butyl methylether (MTBE), a high octane fuel additive.
Note that there are three consequences to the formation of carbocationintermediates:
1. Markovnikovs rule holds.
2. Addition of H and OH occurs in both syn and anti fashion.
3. Carbocation rearrangements can occur.
Electrophilic Addition of Alcohols to C=C
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Halogenation is the addition of X2 (X = Cl or Br) to an alkene to form avicinal dihalide.
Electrophilic Addition of Halogen to C=C
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Carbocations are unstable because theyhave only six electrons around carbon.Halonium ions are unstable because of
ring strain.
Electrophilic Addition of Halogen to C=C
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Consider the chlorination of cyclopentene to afford both enantiomers oftrans-1,2-dichlorocyclopentane, with no cis products.
Initial addition of the electrophile Cl+ from (Cl2) occurs from either sideof the planar double bond to form a bridged chloronium ion.
Electrophilic Addition of Halogen toC=C: Stereochemistry
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In the second step, nucleophilic attack of Cl must occur from the backside.
Since the nucleophile attacks from below and the leaving group departs fromabove, the two Cl atoms in the product are oriented trans to each other.
Backside attack occurs with equal probability at either carbon of the three-membered ring to yield a racemic mixture.
Electrophilic Addition of Halogen toC=C: Stereochemistry
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cis-2-Butene yields two enantiomers, whereas trans-2-butene yields a single
achiral meso compound.
Halogenation of c is- and trans-2-butene
Electrophilic Addition of Halogen toC=C: Stereochemistry
Electrophilic Addition of Halogen in
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Treatment of an alkene with a halogen X2 and H2O forms a halohydrin byaddition of the elements of X and OH to the double bond.
Electrophilic Addition of Halogen inWater to C=C: Halohydrin Formation:
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Even though X is formed in step [1] of the mechanism, its concentration issmall compared to H2O (often the solvent), so H2O and not X is thenucleophile.
Electrophilic Addition of Halogen inWater to C=C: Halohydrin Formation:
i i A i i f i
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Electrophilic Addition of Halogen inWater to C=C: Halohydrin Formation:
El hili Addi i C C
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Hydroborationoxidation is a two-step reaction sequence that
converts an alkene into an alcohol.
Electrophilic Addition to C=C:Hydroboration - Oxidation
El hili Addi i C C
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With unsymmetrical alkenes, the boron atom bonds to the less substituted
carbon atom.
Electrophilic Addition to C=C:Hydroboration - Oxidation
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Bi t f ti f C C
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Biotransformation of C=C:
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Biotransformation of C=C:
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KEY CONCEPTS
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KEY CONCEPTS
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KEY CONCEPTS
El t hili Additi t C C
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Electrophilic Addition to C
C
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Electrophilic Addition to CC
El t hili Additi t C C
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Electrophilic Addition to C
C
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Problems
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Problems
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Organic Chemistry
For USTH Students
Lecture 3:
Electrophilic substitution inAromatic systems
Dr. Doan Duy Tien
El hili b i i i A i
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Electrophilic substitution in Aromatic systems
Contents:
+ The General Mechanism
+ Halogenation
+ Nitration and Sulfonation
+ Nitration and Sulfonation
+ Substituted Benzenes: Inductive Effects, Resonance Effects
+ Electrophilic Aromatic Substitution of Substituted Benzenes
+ Application : Synthesis of the hallucinogenic effects of LSD
I t ti b i
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Interesting benzene rings
St t f b
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Structure of benzene
Aromaticity-Hckels Rule:
+ A molecule must be cyclic
+ A molecule must be planar+ A molecule must be completely conjugated+ A molecule must satisfy Hckels rule, and contain a particular numberof electrons. An aromatic compound must contain 4n + 2 electrons (n= 0, 1, 2, and so forth).
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Antimalarial drugthat reduces feverDrug for the treatment of type2 diabetes; that increases the
bodys ability to lower blood
sugar levels,
Aromaticity-Hckels Rule ?
A ti it H k l R l ?
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Aromaticity-Hckels Rule ?
Buckminsterfullerene, C60
Mg
NN
NN
OMeOOCO
O phytyl
phytyl =
chlorophyll a
E
1
R R
1
2
34
5
6
7
8
9
10
11
12
13141516
17
18
19
20
Molecule of life
Electrophilic Aromatic Substitution
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Electrophilic Aromatic Substitution
The characteristic reaction of benzene is electrophilic aromaticsubstitution: a hydrogen atom is replaced by an electrophile.
Background:
Electrophilic Aromatic Substitution
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Benzene does not undergo addition reactions likeother unsaturated hydrocarbons, because addition
would yield a product that is not aromatic.
Substitution of a hydrogen keeps the aromatic ring
intact. There are five common examples of electrophilic
aromatic substitution.
Electrophilic Aromatic Substitution
Background:
Electrophilic Aromatic Substitution
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Electrophilic Aromatic Substitution
Mechanism:
Electrophilic Aromatic Substitution
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The energy changes in electrophilic aromatic
substitution are shown below:Figure 18.2 Energy diagram for electrophilic aromatic substitution:
PhH + E+ PhE + H+
Electrophilic Aromatic Substitution
Background:
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Figure 18.1Five examples
of electrophilic
aromaticsubstitution
Electrophilic Aromatic Substitution
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Nitration and sulfonation introduce two differentfunctional groups into the aromatic ring.
Nitration is especially useful because the nitro group
can be reduced to an NH2 group.
Nitration and Sulfonation:
Electrophilic Aromatic Substitution
Electrophilic Aromatic Substitution
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Generation of the electrophile in nitration requires
strong acid.
Electrophilic Aromatic Substitution
Nitration and Sulfonation:
Generation of the electrophile in sulfonation requires
strong acid.
Electrophilic Aromatic Substitution
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In Friedel-Crafts alkylation, treatment of benzene withan alkyl halide and a Lewis acid (AlCl3) forms an alkyl
benzene.
Friedel-Crafts Alkylation and Friedel-Crafts Acylation:
Electrophilic Aromatic Substitution
Electrophilic Aromatic Substitution
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In Friedel-Crafts acylation, a benzene ring is treatedwith acid chloride (RCOCl) and AlCl3 to form a ketone.
Because the new group bonded to the benzene ring is
called an acyl group, the transfer of an acyl group from
one atom to another is an acylation.
Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation and Friedel-Crafts Acylation:
Electrophilic Aromatic Substitution
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Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation:
Electrophilic Aromatic Substitution
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Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation:
Electrophilic Aromatic Substitution
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Four additional facts about Friedel-Crafts alkylationshould be kept in mind:
[1] Vinyl halides and aryl halides are less reactive than
alkyl halides so do not react in Friedel-Crafts alkylation.
Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation:
[2] Alkyl groups activate the benene ring toward further
EAS so polyalkylation can occur.
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Electrophilic Aromatic Substitution
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Electrophilic Aromatic Substitution
Friedel-Crafts Alkylation:
Electrophilic Aromatic Substitution
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Each carbocation can then go on to react with benzene
to form a product of electrophilic aromatic substitution.
For example:
p
Starting materials that contain both a benzene ring and
an electrophile are capable of intramolecular Friedel-
Crafts reactions.
Friedel-Crafts Alkylation and Friedel-Crafts Acylation:
Electrophilic Aromatic Substitution
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Considering the inductive effect, the NH2 group
withdraws electron density. The CH3 donates electron
density through hyperconjugation.
Electrophilic Aromatic Substitution
Substituted Benzenes:
Electrophilic Aromatic Substitution
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Resonance effects are only observed with substituents
containing lone pairs or bonds.
An electron-donating resonance effect is observed
whenever an atom Z having a lone pair of electrons is
directly bonded to a benzene ring.
Electrophilic Aromatic Substitution
Substituted Benzenes:
Electrophilic Aromatic Substitution
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An electron-withdrawing resonance effect is observed
in substituted benzenes having the general structure
C6H5-Y=Z, where Z is more electronegative than Y.
Seven resonance structures can be drawn for
benzaldehyde (C6H
5CHO). Because three of them place
a positive charge on a carbon atom of the benzene ring,
the CHO group withdraws electrons from the benzene
ring by a resonance effect.
Electrophilic Aromatic Substitution
Substituted Benzenes:
Electrophilic Aromatic Substitution
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The inductive and resonance effects in compoundshaving the general structure C6H5-Y=Z (with Z more
electronegative than Y) are both electron withdrawing.
Substituted Benzenes:
Electrophilic Aromatic Substitution
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These compounds represent examples of the generalstructural features in electron-donating and electron
withdrawing substituents.
Electrophilic Aromatic Substitution
Substituted Benzenes:
Electrophilic Aromatic Substitution
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First, consider tolueneToluene reacts faster thanbenzene in all substitution reactions.
The electron-donating CH3 group activates the
benzene ring to electrophilic attack.
Ortho and para products predominate.
The CH3 group is called an ortho, para director.
Electrophilic Aromatic Substitution
EAS and Substituted Benzenes:
Electrophilic Aromatic Substitution
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Now consider nitrobenzeneIt reacts more slowlythan benzene in all substitution reactions.
The electron-withdrawing NO2 group deactivates the
benzene ring to electrophilic attack.
The meta product predominates.
The NO2 group is called a meta director.
Electrophilic Aromatic Substitution
EAS and Substituted Benzenes:
Electrophilic Aromatic Substitution
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All substituents can be divided into three general types:
Electrophilic Aromatic Substitution
EAS and Substituted Benzenes:
Electrophilic Aromatic Substitution
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p
EAS and Substituted Benzenes:
Electrophilic Aromatic Substitution
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To understand how substituents activate or deactivate
the ring, we must consider the first step inelectrophilic aromatic substitution.
The first step involves addition of the electrophile (E+)
to form a resonance stabilized carbocation.
The Hammond postulate makes it possible to predictthe relative rate of the reaction by looking at the
stability of the carbocation intermediate.
EAS and Substituted Benzenes:
Electrophilic Aromatic Substitution
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p
EAS and Substituted Benzenes:
Electrophilic Aromatic Substitution
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Orientation Effects in Substituted Benzenes:
There are two general types of ortho, para directors
and one general type of meta director.
All ortho, para directors are R groups or have a
nonbonded electron pair on the atom bonded to the
benzene ring.
All meta directors have a full or partial positive charge
on the atom bonded to the benzene ring.
p
Electrophilic Aromatic Substitution
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Figure 18.7 The reactivity anddirecting effects of common
substituted benzenes
p
Orientation Effects in Substituted Benzenes:
Electrophilic Aromatic Substitution
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Limitations in Electrophilic Aromatic Substitutions:
Benzene rings activated by the strong electron-
donating groups, OH, NH2, and their derivatives (OR,NHR, and NR2), undergo polyhalogenation when
treated with X2 and FeX3.
Electrophilic Aromatic Substitution
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A benzene ring deactivated by strong electron-
withdrawing groups (i.e., any of the meta directors)is not electron rich enough to undergo Friedel-Crafts
reactions.
Friedel-Crafts reactions also do not occur with NH2groups because the complex that forms between the
NH2 group and the AlCl3 catalyst deactivates the ring
towards Friedel-Crafts reactions.
Limitations in Electrophilic Aromatic Substitutions:
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Electrophilic Aromatic Substitution
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2. If the directing effects of two groups oppose eachother, the more powerful activator controls the
reaction.
Disubstituted Benzenes:
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Electrophilic Aromatic Substitution
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Planning Synthesis of Benzene Derivatives:
In a disubstituted benzene, the directing effects indicatewhich substituent must be added to the ring first.
Let us consider the consequences of bromination firstfollowed by nitration, and nitration first, followed by
bromination.
Electrophilic Aromatic Substitution
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Pathway I, in which bromination precedes nitration,
yields the desired product. Pathway II yields the
undesired meta isomer.
Electrophilic Aromatic Substitution
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Halogenation of Alkyl Benzenes:
Electrophilic Aromatic SubstitutionHalogenation of Alkyl Benzenes:
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Note that alkyl benzenes undergo two different
reactions depending on the reaction conditions:
With Br2 and FeBr3 (ionic conditions), electrophilic
aromatic substitution occurs, resulting in replacementof H by Br on the aromatic ring to form o and p isomers.
With Br2 and light or heat (radical conditions),
substitution of H by Br occurs at the benzylic carbon of
the alkyl group.
Halogenation of Alkyl Benzenes:
Electrophilic Aromatic Substitution
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Oxidation and Reduction of Substituted Benzenes:
Arenes containing at least one benzylic CH bond are
oxidized with KMnO4 to benzoic acid.
Substrates with more than one alkyl group are
oxidized to dicarboxylic acids. Compounds without
a benzylic hydrogenare inert to oxidation.
Electrophilic Aromatic Substitution
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We now know two different ways to introduce an alkyl
group on a benzene ring:
1. A one-step method using Friedel-Crafts alkylation.
2. A two-step method using Friedel-Crafts acylation to
form a ketone, followed by reduction.
Figure 18.8 Twomethods to prepare
an alkyl benzene
Oxidation and Reduction of Substituted Benzenes:
Electrophilic Aromatic Substitution
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Although the two-step method is longer, it must be
used to synthesize certain alkyl benzenes thatcannot be prepared by the one-step Friedel-Crafts
alkylation because of possible rearrangements.
Oxidation and Reduction of Substituted Benzenes:
Electrophilic Aromatic Substitution
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A nitro group (NO2) that has been introduced on abenzene ring by nitration with strong acid can
readily be reduced to an amino group (NH2) under a
variety of conditions.
Oxidation and Reduction of Substituted Benzenes:
Electrophilic substitution in Aromatic systems
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Electrophilic substitution in Aromatic systems
+ Application : Synthesis of the hallucinogenic effects of LSD
El t hili b tit ti i A ti t
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Application: Swimming pool test kit forchlorine
97
NH2
Cl2(aq.)
NH2
CH3
Cl
ClCH3
o-toluidine
bright yellow!
Electrophilic substitution in Aromatic systems
Electrophilic substitution in Aromatic systems
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Naproxen production: Albemarle Company
Anti-inflammatory drugHeck Coupling: Nobel prize 2010:
KEY CONCEPTS
http://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drughttp://en.wikipedia.org/wiki/Nonsteroidal_anti-inflammatory_drug -
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KEY CONCEPTS
KEY CONCEPTS
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Problems
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Reaction of Carbocation
Key intermediate for biosynthesis