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 Chapter 4:
Alkyne Hydrocarbon
Alkene Arene
1.Preparation 1.Preparation 1.Preparation
2.Chemical 2.Chemical properties 2.Chemical
properties properties
 Chapter 4:
Alkyne Hydrocarbon
Alkene Arene
1.Preparation 1.Preparation 1.Preparation
2.Chemical 2.Chemical properties 2.Chemical
properties properties
Alkene

ALKENE
- unsaturated hydrocarbons
- 1 double bond “=”
-formula : CnH2n (n ≥ 2)
Alkene 1. Preparation
- Dehydrations of alcohols
 Alkene 1. Preparation
E1 Elimination : secondary and tertiary
* Tertiary
Alkene 1. Preparation
Alkene 1. Preparation
 Alkene 1. Preparation
E1 Elimination : secondary and tertiary
* Secondary
Alkene 1. Preparation
Regioselectivity of Dehydration Reactions
Alkene 1. Preparation
Rearrangements in Dehydration Reactions
Alkene 1. Preparation
Rearrangements in Dehydration Reactions
Alkene 1. Preparation
E2 Elimination : primary
Alkene 1. Preparation
Rearrangements in Dehydration of Primary Alcohols
Alkene 2.Chemical properties
Addition reactions
 Alkene 2.Chemical properties
Addition reactions
+ HX (hydrohalogenation)
 Alkene 2.Chemical properties
Addition reactions
+ HX (hydrohalogenation)
 Alkene 2.Chemical properties
Addition reactions
+ HX (hydrohalogenation)
 Alkene 2.Chemical properties
Addition reactions
+ HX (hydrohalogenation)

 Markovnikov’s rule
 Alkene 2.Chemical properties
Addition reactions
+ HX (hydrohalogenation)

Example: base on Markovnikov’s rule, find the product

Alkene 2.Chemical properties

Radical intermediates
(ROOR) which is is
efficient for the addition of
HBr but not HCl or HI
 Alkene 2.Chemical properties
Addition reactions
+ HX (hydrohalogenation)
MECHANISM
 Alkene 2.Chemical properties
Addition reactions
+ HX (hydrohalogenation)
STEREOCHEMISTRY
 Alkene 2.Chemical properties
Addition reactions
+ HX (hydrohalogenation)
REARRANGEMENT
 Alkene 2.Chemical properties
Addition reactions
+ H2O, H2SO4 (acid catalyzed hydration)

The rate of an acid-catalyzed hydration is very much

dependent on the structure of the starting alkene

OH is placed in each of the cases above: at the

more substituted position
 Alkene 2.Chemical properties
Addition reactions
+ H2O, H2SO4 (acid catalyzed hydration)
MECHANISIM
 Alkene 2.Chemical properties
Addition reactions
+ H2O, H2SO4 (acid catalyzed hydration)
MECHANISIM

Example
In each of the following cases identify the alkene that is expected to be more reactive
toward acid-catalyzed hydration.
 Alkene 2.Chemical properties
Addition reactions
+ H2O, H2SO4 (acid catalyzed hydration)
MECHANISIM
Solution
By controlling the amount of water present (using either concentrated acid or
dilute acid), one side of the equilibrium can be favored over the other:

Le Châtelier’s principle

Water can also be removed from the system via a distillation process, which
would also favor the alkene.
 Alkene 2.Chemical properties
Addition reactions
+ H2O, H2SO4 (acid catalyzed hydration)
STEREOCHEMISTRY
 Alkene 2.Chemical properties
Addition reactions
+B2H6 – Oxidation (hydroboration - oxidation)

 H and OH on the same face of the π bond

 syn addition
 Alkene 2.Chemical properties
Addition reactions
+Hydroboration
 Alkene 2.Chemical properties
Addition reactions
+Hydroboration
 Alkene 2.Chemical properties
Addition reactions
+Hydroboration
Example:
 Alkene 2.Chemical properties
Addition reactions
+Hydroboration
Example:
 Alkene 2.Chemical properties
Addition reactions
+ H2 (catalytic hydrogenation)
unsaturated  saturated
 Alkene 2.Chemical properties
Addition reactions
+ H2 (catalytic hydrogenation)
Stereospecificity
two new chirality centers are being formed
 Alkene 2.Chemical properties
Addition reactions
+ H2 (catalytic hydrogenation)
Stereospecificity

Example
 Alkene 2.Chemical properties
Addition reactions
+ H2 (catalytic hydrogenation)
Stereospecificity
 Alkene 2.Chemical properties
Addition reactions
+ H2 (catalytic hydrogenation)
Homogeneous Catalysts homogeneous catalysts are soluble in the reaction medium.
 Alkene 2.Chemical properties
Addition reactions
+ X2 (X: Cl, Br) (halogenation)
 Alkene 2.Chemical properties
Addition reactions
+ X2 (X: Cl, Br) (halogenation)
Mechanism
 Alkene 2.Chemical properties
Addition reactions
+ X2 (X: Cl, Br) (halogenation)
Cis-trans distinguish
 Alkene 2.Chemical properties
Addition reactions
+ X2 (X: Cl, Br) (halogenation)
Example
 Alkene 2.Chemical properties
Oxidation reactions
+ Anti dihydroxylation (peracid – RCOOOH)
 Alkene 2.Chemical properties
Oxidation reactions
+ Anti dihydroxylation (peracid – RCOOOH)
 Alkene 2.Chemical properties
Oxidation reactions
+ Anti dihydroxylation (peracid – RCOOOH)
Example
 Alkene 2.Chemical properties
Oxidation reactions
+ Anti dihydroxylation (peracid – RCOOOH)
Example
 Alkene 2.Chemical properties
Oxidation reactions
+ Syn dihydroxylation (OsO4 hoặc KMnO4)
 Alkene 2.Chemical properties
Oxidation reactions
+ Syn dihydroxylation (OsO4 hoặc KMnO4)
KMnO4
 Alkene 2.Chemical properties
Oxidation reactions
+ Ozonolysis - O3, DMS

Ozone is a compound with the following resonance structures

 Alkene 2.Chemical properties
Oxidation reactions
+ Ozonolysis - O3, DMS
 Alkene 2.Chemical properties
Oxidation reactions
+ Ozonolysis - O3, DMS
 Alkene 2.Chemical properties
Oxidation reactions
+ Ozonolysis - O3, DMS
Alkene
 Chapter 4:
Alkyne Hydrocarbon
Alkene Arene
1.Preparation 1.Preparation 1.Preparation
2.Chemical 2.Chemical properties 2.Chemical
properties properties
Alkyne

ALKYNE
-unsaturated hydrocarbons
-1 triple bond “≡”
-formula :CnH2n-2 (n ≥ 2)
 Alkyne 1. Preparation
E2 Elimination
 Alkyne 1. Preparation
E2 Elimination
Example
 Alkyne 2. Chemical properties
• Reduction of alkynes
 Alkyne 2. Chemical properties
• Reduction of alkynes
Example
 Alkyne 2. Chemical properties
• Reduction of alkynes
Example
Prepare the following compounds:
+pentane +cis-4-methyl-2-pentene +trans-4-bromo-2-pentene.
 Alkyne 2. Chemical properties
• Reduction of alkynes
Example
SOLUTION:
 Alkyne 2. Chemical properties
• Hydrohalogenation
 Alkyne 2. Chemical properties
• Hydrohalogenation
Mechanism
 Alkyne 2. Chemical properties
• Hydrohalogenation
Mechanism
 Alkyne 2. Chemical properties
• Hydrohalogenation
HBr: anti-Markovnikov
 Alkyne 2. Chemical properties
• Hydrohalogenation
Example
 Alkyne 2. Chemical properties
• Hydrohalogenation
Solution
 Alkyne 2. Chemical properties
• Hydrohalogenation
Solution
 Alkyne 2. Chemical properties
• Hydration - Acid catalyzed hydration
Markovnikov’s rule
 Alkyne 2. Chemical properties
• Hydration - Acid catalyzed hydration
Mechanisim
 Alkyne 2. Chemical properties
• Hydration - Acid catalyzed hydration
Mechanisim
 Alkyne 2. Chemical properties
• Hydroboration
 Alkyne 2. Chemical properties
• Hydroboration
Mechanism
 Alkyne 2. Chemical properties
• Hydroboration
 Alkyne 2. Chemical properties
• Halogenation
 Alkyne 2. Chemical properties
• Halogenation
Mechanism
 Alkyne 2. Chemical properties
• Ozonolysis
 Alkyne 2. Chemical properties
• Alkylation

 2 steps
 Alkyne 2. Chemical properties
• Alkylation
Example
 Alkyne 2. Chemical properties
• Alkylation
Example
 Chapter 4:
Alkyne Hydrocarbon
Alkene Arene
1.Preparation 1.Preparation 1.Preparation
2.Chemical 2.Chemical properties 2.Chemical
properties properties
 Arene 2. Chemical properties
1. Electrophilic Substitution
The most common reaction of aromatic compounds is electrophilic aromatic
substitution (SEAr), in which an electrophile (E+) reacts with an aromatic ring and
substitutes for one of the hydrogens.
 Arene 2. Chemical properties
1. Electrophilic Substitution

Through electrophilic substitution,

an aromatic ring can be substituted
by a halogen (-Cl, -Br, -I), a nitro
group (-NO2), a sulfonic acid group
(- SO3H), a hydroxyl group (-OH),
an alkyl group (-R), or an acyl group
(-COR).
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Halogenation Halogenation-bromination
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Halogenation Halogenation-bromination
In this reaction, the hydrogen in the aromatic ring will be replaced by the electrophile
Br+ to form the product Bromide Benzene.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Halogenation Halogenation-chlorination
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Halogenation Halogenation-chlorination
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Halogenation Halogenation-chlorination
A General Mechanism for Electrophilic Aromatic Substitution
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Halogenation Halogenation-chlorination
Example:
Draw the mechanism of the following reaction, and make sure to draw all
three resonance structures of the sigma complex.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Halogenation Halogenation-chlorination
Solution
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Nitration
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Nitration
Electrophilic nitration of an aromatic ring does not occur in nature but is particularly
important in the laboratory because the nitro-substituted productcan be reduced by reagents
such as iron, tin, or SnCl2 to yield an arylamine, ArNH2. Attachment of an amino group to an
aromatic ring by the two-step nitration/reduction sequence is a key part of the industrial
synthesis of many dyes and pharmaceutical agents.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Nitration
Example:
Draw the mechanism of the following reaction, and make sure to draw all
three resonance structures of the sigma complex.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Nitration
Solution
 Arene 2. Chemical properties
1. Electrophilic Substitution
• Sulfonation
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALKYLATION
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALKYLATION
General mechanism
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALKYLATION
Example
Draw the mechanism of the following reaction, and make sure to draw all three
resonance structures of the sigma complex.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALKYLATION
Solution
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALKYLATION
Limitations of Friedel–Crafts alkylation
1. When choosing an alkyl halide, the carbon atom connected to the halogen must be
sp3 hybridized. Vinyl carbocations and aryl carbocations are not sufficiently stable to
be formed under Friedel-Crafts conditions.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALKYLATION
Limitations of Friedel–Crafts alkylation
2. Installation of an alkyl group activates the ring toward further alkylation (for
reasons that we will explore in the upcoming sections of this chapter). Therefore,
polyalkylations often occur.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALKYLATION
Limitations of Friedel–Crafts alkylation
2.

This problem can generally be avoided by choosing reaction conditions that favor
monoalkylation. For the remainder of this chapter, assume that all Friedel-Crafts
alkylations are performed under conditions that favor monoalkylation, unless
otherwise specified.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALKYLATION
Limitations of Friedel–Crafts alkylation
3. There are certain groups, such as a nitro group, that are incompatible with a
Friedel-Crafts reaction. In the upcoming sections of this chapter, we will explore the
reason for this incompatibility.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALCYLATION

The difference between an alkyl group and an acyl group is shown below.
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALCYLATION
Mechanism
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALCYLATION
Mechanism with all three resonance structures of the sigma complex
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALCYLATION
Mechanism with all three resonance structures of the sigma complex
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALCYLATION
Example
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALCYLATION
Solution
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALCYLATION
Solution
 Arene 2. Chemical properties
1. Electrophilic Substitution
• FRIEDEL-CRAFTS ALCYLATION
Solution
 Arene 2. Chemical properties
2. REACTION OF SUBSTITUTED BENZEN;

•C1) For benzene due to the 6 carbon atoms being the same, a one-time substitution
gives a single product

• C2) If there is a substituent in the benzene nucleus, these substituents greatly affect
the reactivity of the aromatic compound and preferentially orient the new substituent
to certain positions.
 Arene 2. Chemical properties
2. REACTION OF
SUBSTITUTED
BENZEN;
Type 1
groups with +I, +C, +H effects, most of
these substituents activate the
aromatic nucleus and preferentially
orient the new substituent to the orto
and para positions
Class I agents are arranged from
strong to weak in the following
sequence: -O, NR2, NHR, NH2, OH,
OR, NHCOR, OCOR, R, OC6H5, X
+ Note: Halogen X group belongs to
the 1st substituent but passivates the
benzene ring
 Arene 2. Chemical properties
2. REACTION OF
SUBSTITUTED
BENZEN;
Type 2
substituents: These are substituents
with -, -C effect, these substituents
deactivate the aromatic nucleus and
preferentially orient the new
substituent to the meta position.

Sort from weak to strong: NO2, CN,

SO3H, CF3, CCL3, CHO, COR, COOH
 Arene 2. Chemical properties
2. REACTION OF
SUBSTITUTED
BENZEN;
Mixed substituents:
Do not give priority to orient the new
substituent to any position, but put the
mixture in o, m, p with the ratio rates
are not much different. For example -
N=O, -CH,F, -CH,-NO,
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Going all the way back to the nucleophilic substitution and elimination reactions , we can remember
that benzylic substrates readily undergo SN1, SN2, E and E2 reactions. For the SN2 and E2
mechanisms, it is simply a matter of having a strong base/nucleophile and a non-hindered carbon
atom:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
On the other hand, the reactivity in unimolecular SN1 and E1 reactions is explained by the resonance-
stabilization of the benzylic carbocation formed in the rate-determining step:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Remember that carbocations are sp2-hybridized and the empty p orbital of the positively charged
carbon is nicely aligned with the p orbitals of the aromatic system which makes the cation resonance-
stabilized:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Don’t confuse the benzylic carbocation with the phenyl carbocation. Yes, they are both sp2 carbons
but unlike the benzylic carbon, the positive charge of the phenyl cation is a result of the empty sp2
orbital which lies perpendicular to the conjugated aromatic system and cannot be resonance stabilized:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
This is the reason, for example, why aryl and vinyl halides do undergo Fidel-Crafts alkylation:
 Arene 2. Chemical properties
3, REACTION AT THE
BENZYLIC POSITION
Halogenation of the Benzylic Position
Chlorination and bromination of the benzylic
position are achieved when Lewis acid
catalyst are not used:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Halogenation of the Benzylic Position
The bromination can also be done using N-Bromosuccinimide (NBS) like in the allylic
bromination:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Halogenation of the Benzylic Position
All the halogenation reactions go by a radical mechanism and the reactivity of the
benzylic carbon is again explained by its resonance-stability. Remember, radicals can
also be resonance-stabilized:
 Arene 2. Chemical properties
3, REACTION AT THE
BENZYLIC POSITION
Oxidation of the Benzylic Carbon
Strong oxidizing agents such as KMnO4 and
Na2Cr2O7 oxidize a primary or secondary
benzylic carbon to the carboxy group. The
only requirement here is to have at least one
hydrogen on the benzylic carbon. Therefore,
the oxidation only works for primary and
secondary alcohols:
 Arene 2. Chemical properties
3, REACTION AT THE
BENZYLIC POSITION
Oxidation of the Benzylic Carbon
Notice that even for longer alkyl groups the
remaining carbon atoms are cleaved off in the
oxidation and benzoic acids are formed.
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Oxidation of the Benzylic Carbon
A mild oxidizing agent can be used to oxidize benzylic alcohols to their corresponding
ketones under carefully chosen conditions:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Reduction of the Benzylic Carbon
Aryl ketones prepared by the Friedel-Crafts acylation can be reduced to alkyl benzenes by
the Clemenson or Wolff-Kishner reactions:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Reduction of the Benzylic Carbon
Notice also that other ketones are reduced to alcohols and only aryl ketones can be
reduced to a methylene group by catalytic hydrogenation (H2 + Pt or Pd/C):
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Reduction of the Benzylic Carbon
Even though this is not a reaction at the benzylic position, I’d still like to add here the
reduction of the nitro group on a benzene ring:Even though this is not a reaction at the
benzylic position, I’d still like to add here the reduction of the nitro group on a benzene
ring:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Reduction of the Benzylic Carbon
This reaction is important since there is no direct way of converting benzene into aniline
which is an essential precursor in the preparation of many aromatic compounds.
It is also used to prepare arenediazonium salts which are again a great source for
performing aromatic transformations.
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Synthetic Strategies
The benzylic oxidation is a great way preparing substituted benzoic acids since the
carboxy group cannot be added directly by electrophilic aromatic substitution and it
allows achieving it through a Friedel-Crafts reaction followed by oxidation:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Synthetic Strategies
In addition, benzene can be converted into ortho, para or a meta activated ring
depending on the order of these reactions.
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Synthetic Strategies
For example, how could you prepare p-Nitrobenzoic acid from benzene?
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Synthetic Strategies
The problem here is that both groups are meta directors.

However, we can first alkylate the benzene ring, followed by nitration and oxidize the resulting p-
Nitrotoluene to p-Nitrobenzoic acid:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Synthetic Strategies
Notice that the reverse order would require a Friedel-Crafts alkylation of the nitrobenzene and Friedel-
Crafts reactions do not generally work with deactivated benzene rings. But even if we pretend they do, it
still gives the undesired meta product:
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Synthetic Strategies
So, how do you prepare the meta Nitrobenzoic acid then?
 Arene 2. Chemical properties
3, REACTION AT THE BENZYLIC POSITION
Synthetic Strategies
Well, since the methylation of nitrobenzene does not work, we need to go the other way, i.e. install the
carboxy group first and then do the nitration which will occur at the meta position since the carbonyl group
is a meta director:
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
Synthetic Strategies
The benzylic C-H bonds weaker than most sp3 hybridized C-H. This is because the radical formed from
homolysis is resonance stabilized.
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
Synthetic Strategies
Resonance stabilization of the benzylic radical
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
Synthetic Strategies
Because of the weak C-H bonds, benzylic hydrogens can form benzylic halides under radical conditions.
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
NBS as a Bromine Source
NBS (N-bromosuccinimide) is the most commonly used reagent to produce low concentrations of bromine.
When suspended in tetrachloride (CCl4), NBS reacts with trace amounts of HBr to produce a low enough
concentration of bromine to facilitate the allylic bromination reaction.
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
Allylic Bromination Mechanism
Step 1: Initiation
Once the pre-initiation step involving NBS produces small quantities of Br2, the
bromine molecules are homolytically cleaved by light to produce bromine radicals.
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
Allylic Bromination Mechanism

Step 2 and 3: Propagation

 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
Allylic Bromination Mechanism

Step 4: Termination
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
REACTION OF TOLUENE WITH Br2
Step 1 (Initiation)
Heat or uv light cause the weak halogen bond to undergo homolytic cleavage to
generate two bromine radicals and starting the chain process.
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
REACTION OF TOLUENE WITH Br2
Step 2 (Propagation)
(a) A bromine radical abstracts a hydrogen to form HBr and a benzyl radical, then
(b) The benzyl radical abstracts a bromine atom from another molecule of Br2 to form
the benzyl bromide product and another bromine radical, which can then itself
undergo reaction 2(a) creating a cycle that can repeat.
 Arene 2. Chemical properties
4, HALOGENATIONS OF ALKYL SUBSTITUENTS
REACTION OF TOLUENE WITH Br2
Step 3 (Termination)
Various reactions between the possible pairs of radicals allow for the formation of Br2
or the product, benzyl bromide. These reactions remove radicals and do not
perpetuate the cycle.
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
DEFINITION:
Nucleophilic aromatic substitution is a classical reaction in which a nucleophile
displaces a leaving group on an aromatic ring. The presence of the electron-
withdrawing group increases the rate of nucleophilic aromatic substitution.
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
Conditions of Nucleophilic Aromatic Substitution
• The nitro group is generally used as an electron-withdrawing group to activate the
aromatic ring for nucleophilic aromatic substitution.
• Ortho or Para position of the electron-withdrawing group to the leaving group
supports the resonance stabilisation of the negative charge in the transition state.
• –OH, –OR, –NH2, –SR, NH3, and other amines are nucleophiles that generally
show nucleophilic aromatic substitution.
• Alike SN1 or SN2 greater the halogen atoms electronegativity, the more readily it
will leave.
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
Addition-Elimination Mechanism of Nucleophilic Substitution of Aryl Halides
Although the simple aryl halides are inert to the usual nucleophilic reagents, considerable activation is
produced by strongly electron-attracting substituents provided these are located in either the ortho or
para positions, or both. For example, the displacement of chloride ion from 1-chloro-2,4-
dinitrobenzene by dimethylamine occurs readily in ethanol solution at room temperature. Under the
same conditions chlorobenzene completely fails to react; thus the activating influence of the two nitro
groups amounts to a factor of at least 108:
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION

A related reaction is that of 2,4-

dinitrofluorobenzene with the amino groups of
peptides and proteins, and this reaction provides
a means for analysis of the N-terminal amino
acids in polypeptide chains.
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
The generally accepted mechanism of nucleophilic aromatic substitution of aryl halides carrying
activating groups involves two steps. The first step involves attack of the nucleophile Y:⊖ at the carbon
bearing the halogen substituent to form an intermediate carbanion. The aromatic system is destroyed
on forming the anion, and the carbon at the reaction site changes from planar (sp2 bonds) to
tetrahedral (sp3 bonds).
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
In the second step, loss of an anion, X⊖ or Y⊖, regenerates an aromatic system, and, if X ⊖ is lost, the
overall reaction is nucleophilic displacement of X by Y.
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
In the case of a neutral nucleophilic reagent, Y or HY, the reaction sequence would be the same except
for the necessary adjustments in the charge of the intermediate:

Why is this reaction pathway generally unfavorable for the simple aryl halides? The answer is that the
intermediate is too high in energy to be formed at any practical rate. Not only has it lost the aromatic
stabilization of the benzene ring, but its formation results in transfer of a negative charge to the ring
carbons, which themselves are not very electronegative.
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
When strongly electron-attracting groups are located on the ring at the ortho-para positions, the
intermediate anion is stabilized by delocalization of electrons from the ring carbons to more favorable
locations on the substituent groups. As an example, consider the displacement of bromine by methoxid
(OCH3) in the reaction of 4-bromonitrobenzene and methoxide ion:
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
The anionic intermediate formed by addition of methoxide ion to the aryl halide can be described by
the valence-bond structures 5a-5d. Of these structures 5d is especially important because in it the
charge is transferred from the ring carbons to the oxygen of the nitro substituent:
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
Substituents in the meta positions have much less effect on the reactivity of an aryl
halide because delocalization of electrons to the substituent is not possible. No
formulas can be written analogous to 5c and 5d in which the negative charges are
both on atoms next to positive nitrogen and
 Arene 2. Chemical properties
5, NUCLEOPHILIC AROMATIC SUBSTITUTION REACTION
In a few instances, stable compounds resembling the postulated reaction intermediate
have been isolated. One classic example is the complex 7 (isolated by J.
Meisenheimer), which is the product of the reaction of either the methyl aryl ether 6
with potassium ethoxide, or the ethyl aryl ether 8 and potassium methoxide:
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