B.Sc.

-VI
Unit-I: Aromatic Substitution Reactions

Dr. Madhu Kumar D J. M.Sc., Ph.D

Assistant Prof. Dept. of Chemistry,
A.D.B. First Grade College, Harapanahalli.
 Aromatic Electrophilic substitution:
Aromatic Electrophilic substitution:
The arenium ion mechanism.
Orientation and reactivity, energy profile
diagram.
The ortho / para ratio, ipso attack, orientation
in other ring system, quantitative treatment of
reactivity in substrates and electrophiles.
Diazonium coupling
Vilsmeir reaction
Gatterman-Koch reaction
 ELECTROPHILIC AROMATIC
SUBSTITUTION
Both BENZENE and ALKENE are susceptible to E +
attack due to their exposed π electrons
ELECTROPHILIC ADDITION IN ALKENE

WHY ELECTROPHILIC ATTACK IN BENZENE?

Theory The high electron density of the ring makes
it open to attack by electrophiles

HOWEVER...
Because the mechanism involves an initial disruption
to the ring, electrophiles will have to be more powerful
than those which react with alkenes.

4
 A fully delocalised ring is stable so will
resist ELECTROPHILIC ADDITION.

A STABLE DELOCALISED SYSTEM DOES NOT FORM THIS PRODUCT SINCE

LESS STABLE THAN STARTING MATERIAL
DUE TO LOSS OF AROMATICITY

ELECTRONS ARE NOT DELOCALISED

AROUND THE WHOLE RING - LESS
STABLE

THEREFORE, BENZENE UNDERGOES SUBSTITUTION

REACTION RATHER THAN ADDITION REACTION
ARENIUM ION, ITS MECHANISM, SE2 REACTION

The general equation for this reaction is:

Although the Wheland intermediate is stabilized by resonance

•we have clearly lost the aromatic stabilization of the starting

material and hence the addition of the electrophile is going to be the
slow step (rds = rate determining step).
•The second step will be fast since we regenerate the aromatic
system by loss of the proton.
STEP II
 ENERGY PROFILE DIAGRAM OF
ARENIUM ION

SUBSTITUTION ELECTROPHILIC BIMOLECULAR (SE2)

Orientation and Reactivity in Monosubstituted Benzenes :
When a monosubstituted benzene undergoes an electrophilic
substitution, the position takes up by the incoming group (the
orientation) and the rate of reaction (the reactivity) are determined
by the substituent already present on the benzene ring. On this basis
various substituents can be divided into three categories.
1. Ortho, paradirecting and activating groups : is attached to the ortho
and para positions. Furthermore, the benzene ring containing a group
of this category is more reactive towards electrophilic substitution
han benzene itself. This is called activation of the benzene ring.
2. Meta-directing and deactivating groups :
If a group of this category is already present on the benzene ring
then the incoming group is attached to the meta-position.
Furthermore, the benzene ring containing a group of this category is
less reactive towards electrophilic substitution than benzene itself.
This is called deactivation of benzene ring.

3. Ortho, para-directing and deactivating groups :

Halogens (F, Cl, Br and I) are ortho and para directing but they
deactivate the benzene ring for further electrophilic substitutions.
Explanation for orientation and reactivity : The effect of substituents
on orientation and reactivity can be best explained by writing all the
possible resonating structures of the carbocation (arenium ion)
intermediate for each of the three possible reaction cources, i.e, for the
attack at o, p and m-positions, and comparing their stability.
Ortho, para-directing and activating groups : The groups containing a lone pair
of electrons on the bey atom stabilise the carbocation to a greater extent when
the attack takes place at the o and p-positions as compared to the attack at the m-
positions. This is because for the attack at ortho and para positions an additional
and particularly stable resonating structure (marked A) can be written in which
all the atoms (except hydrogen) have a complete octet of electrons. Thus, the
incoming electrophile is attached to the o and p-positions, i.e., these groups are
op- directing. Electron donation by such groups (z) increases the rate of
substitution compared to that in benzene itself, thus, these are activating groups.

Attack at ortho position :

Attack at p-position :

Attack at m-position :
b) In the case of alkyl groups the following resonating structures
can be written :
Attack at ortho position :

Attack at para position :

 Attack at meta position :

In the case of ortho and para attacks there is one resonating structure
(marked A) in each case which is particularly stable because it contains
the electron-releasing alkyl group attached to the carbon carrying the
positive charge. No such resonating structure can be written in the case
of meta attack.
• The resonating structures marked A are tertiary carbocations.
•Thus, in the case of alkylbenzenes ortho and para substitution is
preferred to meta.
•Electron donation by alkyl groups increases the rate of substitution
compared to that in benzene itself, thus, these are activating groups.
Meta directing and deactivating groups :
+ +
•The substituents like NH3+ , NR3 , NO2, CF3, CN, SO3H, CHO,
COR, COOH, COOR,etc.
•These substituents are strongly electron with drawing and deactivate
all the ring positions compared to that of benzene.
•More deactivating for the o and p positions than for m-position.
•The substitution takes place at slower rate than benzene and occurs
preferably at m-positions
Attack at ortho position :

Attack at para position :

Attack at meta position :

 Orientation in Other Ring Systems
Unlike benzene, in fused ring hydrocarbons the positions are not
equivalent and there is a preferred orientation even in the
unsubstituted hydrocarbon. For example, in naphthalene the α-
position (position 1) is preferred site of attack, i.e., it is more
reactive than the β- possition (position 2). This is because the
intermediate formed after the attack at α-position is stabilised by
two resonating structures retaining one benzene ring, while only
one such structure can be written in the case of the attack at β -
position.
Inductive donors and acceptors:
•Simple alkyl groups are donating due to hyperconjugation.
•The trifluoromethyl group is electron- withdrawing due to its
electronegative fluorines .
•Directly bound heteroatoms (N, O, halogens) are electron-
withdrawing due to their electronegativities.
•Positively polarized atoms (carbonyl, cyano, nitro and sulfonyl) are
also electron-withdrawing.
Electron-donating groups increase the electron density in the
benzene ring (red) while electron-withdrawing groups decrease
the electron density in the ring (blue).

Since the attacking species is an electrophile, the more electron

rich the arene, the faster the reaction. Electrons donors activate
the ring: Electron acceptors deactivate the ring.
 Steric Effects and Ortho/Para Ratios in Aromatic Electrophilic
Substitution
When a monosubstituted benzene containing an o-p-directing group
undergoes electrophilic substitution, mainly o-and p-substituted products
are obtained. Since, there are two ortho positions available compared to
only one para position, it may be expected that the o and p-isomers
should be formed in 2 : 1 ratio. However, in actual practice this o/p ratio
is less. Several factors like steric hindrance, polar effect. (Inductive and
resonance) of the substituent, solvent effect, temperature, etc. effect the
o/p ratio.
Because of the steric hindrance involved in the T.S. for ortho
substitution, the proportion of ortho isomer decreases as the size of the
o-p-directing group already present on the benzene ring increases, or
the size of the attacking electrophile increases. For example, in the
nitration of toluene and t-butyl benzene under the same conditions,
toluene gives 58% of the ortho compound and 37% of the para, whereas
the latter with the more bulky t-butyl group gave 16% of the ortho
product of 73% of the para.
First H2SO4 donates a proton to SO3 to produce HSO3+ (the
reactive species)
 Diazo Compounds

Compounds containing -N=N- group are known as diazo compounds.

Their general structure is R-N=N-R’
Here R and R’ are preferably arene groups and the azo group is thus
stabilised by becoming part of extended delocalised system. They are
prepared by coupling reaction between a diazonium salt and a
coupling reagent.
Diazonium salts are prepared by adding cold solution of sodium
nitrite (NaNO2) to arylamine solution in dilute acid below 5oC
temperature. This process is called diazotisation. The diazonium
salts are prepared fresh and used immediately.
The hydrochloric acid reacts with sodium nitrite to form unstable
nitrous acid.
The nitrous acid formed in situ reacts with the arylamine to
form diazonium ion.

Mechanism of diazotization

Step 1: Formation or generation of NO (nitrosonium ion) or

+

dinitrogentrioxide: The nitrosonium ion formation takes place

as follows where water is removed from nitrous acid.
Step 2: Attack of NO+ (nitrosonium ion) or N2O3 on the amine

Step 3: Loss of proton

 Step 4: Tautomerisation

Step 5: Loss of water and formation or generation of

diazonium ion
Vilsmeir- Haack Reaction
The reaction of electron-rich aromatic compounds with N,N-
dimethylformamide (DMF) and phosphorus oxychloride
(POCl ) to yield an aromatic aldehyde is called the
3

Vilsmeier–Haack reaction.

Reagents used in Vilsmeier–Haack reaction

The Vilsmeier complexes employed in the formylation reactions
are usually derived from N,Ndisubstituted amide and POCl .
3
Solvents: When liquid amides are used as solvents, excess can be used,
e.g DMF, dimethyl acetamide, N-methyl pyrrolidone, etc. Other
solvents have also been used like benzene, toluene, chloroform,
methylchloride, o-dichlorobenzene, dioxane and tetrahydrofuran

Mechanism of Vilsmeier-Haack reaction

The formylating agent is a chloromethyl iminium salt, also called the

Vilsmeier complex.
 Gattermann Koch Reaction
Gattermann Koch reaction involves the reaction of benzene with CO and
HCl in the presence of Lewis catalysts e.g., AlCl3 to form benzaldehyde.

Gattermann Koch reaction is a variant of the Gattermann chemical

reaction in which carbon monoxide is used instead of hydrogen
cyanide. It is an example of an electrophilic substitution reaction. Here,
benzene reacts with carbon monoxide in an acidic medium in the
presence of anhydrous aluminium chloride or cuprous chloride. The
aluminium chloride or cuprous chloride works as a catalyst to give
Benzaldehyde.
The mechanism of the Gattermann Koch reaction can be explained in 3
steps as follow:

Step 1: Generation of reactive species – Formyl chloride

In the first step, carbon monoxide reacts with HCl to form formyl
chloride. Carbon monoxides act as a lewis acid and accept a proton
from HClHCl. An intermediate having two resonance structures is
formed. Cl− attacks the carbon resulting in the formation of Formyl
chloride.
Step 2: Interaction with AlCl3
The formyl chloride formed in step 1 reacts with the AICl3 to form an
electrophile. Thus, the formyl cation is free to react with benzene.

Step 3: Formation of Benzaldehyde

Benzene is electron-rich and acts as a nucleophile. Therefore, it attacks the
electrophile formed in step 2, forming Benzaldehyde. As a result, the AlCl4 is
converted back to AlCl3.
Nucleophilic Substitution Reactions
SNAr Mechanism
The introduction of electron withdrawing group (EWG) on the
aromatic nucleus makes the system susceptible to nucleophilic
attack. The mechanism is similar to that of electrophilic substitution
except that an anion rather than a cation intermediate is involved.
The nucleophile adds to the aromatic ring to afford a delocalized
anion from which the leaving group (LG) is eliminated.
The delocalization of the negative charge can occur only when the
nucleophile adds to the ortho or para position with respect to the
EWG. Addition to meta position gives an adduct stabilized by the
inductive effect, but not the mesomeric effect. Therefore, towards
nucleophiles, EWG are activating and ortho, para-orienting and, in
contrast, electron donating group (EDG) deactivating and meta
directing. These principles are opposite of those that apply to
electrophilic substitution.
SN1 Mechanism
This mechanism operates in the reaction of diazonium salts with
nucleophiles. The driving force resides in the strength of the bonding in
the nitrogen molecule that makes it a particularly good leaving group.
 Benzyne Mechanism

Aryl halides that have no activating groups proceed reactions with

strong base to give benzyne intermediate which undergoes reaction with
nucleophile to give a mixture of regioisomers.
 SRN1 Mechanism: R stands for radical
SRN1 reactions takes place via free-radical intermediate and have
wide substrate scope. Besides initiation by solvated electrons, they
are also initiated photochemically, electrochemically and even
thermally.
Unactivated aryl halides proceed nucleophilic substitution with
typically enolates, amide ion and thiol anion via a chain reaction
involving anion radicals in that the initiation step is an electron
transfer. The first two steps are similar to those in SN1 reaction
which led to the designation SRNI (R for radical).
 The Substrate in SN1Reactions
SN1 reactions follow first order kinetics due to a multi-step mechanism in
which the rate-determining step consists of the ionization of the alkyl halide to
form a carbocation.
The transition state for the rate determining step shows the transition of an
alkyl halide to a carbocation. Because the rate determining step is
endothermic, the Hammond postulate says that the transition state more
closely resembles the carbocation intermediate. Factors which stabilize this
intermediate will lower the energy of activation for the rate determining step
and cause the rate of reaction to increase. In general, a more stable
carbocation intermediate formed during the reaction allows for a faster the
SN1 reaction rate.
the stability of alky carbocations was shown to be 3o > 2o > 1o > methyl. Two
special cases of resonance-stabilized carbocations, allyl and benzyl, must be
considered and added to the list. The delocalization of the positive charge over
an extended p orbital system allows for allyl and benzyl carbocations to be
exceptionally stable. The resonance hybrid of an allyic cation is made up of
two resonance forms while the resonance hybrid of the benzylic carbocation is
made up of five.
 Effects of Leaving Group
Since leaving group removal is involved in the rate-determining step of the
SN1 mechanism, reaction rates increase with a good leaving group. A good
leaving group can stabilize the electron pair it obtains after the breaking of the
C-Leaving Group bond faster. Once the bond breaks, the carbocation is
formed and the faster the carbocation is formed, the faster the nucleophile can
come in and the faster the reaction will be completed.
The two reactions below only vary by the different leaving groups in each
reaction. The reaction with a more stable leaving group is significantly faster
than the other. This is because the better leaving group leaves faster and thus
the reaction can proceed faster.

The Nucleophile
Since nucleophiles only participate in the fast second step, their relative
molar concentrations rather than their nucleophilicities should be the primary
product-determining factor. If a nucleophilic solvent such as water is used,
its high concentration will assure that alcohols are the major product.
Note that SN1 reactions in which the nucleophile is also the solvent are
commonly called solvolysis reactions. The SN1 reaction of allyl bromide in
methanol is an example of what we would call methanolysis, while if water
is the solvent the reaction would be called hydrolysis:
The strength of the nucleophile does not affect the reaction rate of SN1
because, as described previously, the nucleophile is not involved in the rate-
determining step. However, if you have more than one nucleophile competing
to bond to the carbocation, the strengths and concentrations of those
nucleophiles affects the distribution of products that you will get. For
example, if you have (CH3)3CCl reacting in water and formic acid where the
water and formic acid are competing nucleophiles, you will get two different
products: (CH3)3COH and (CH3)3COCOH. The relative yields of these
products depend on the concentrations and relative reactivities of the
nucleophiles.
 Goldberg Reaction
The Goldberg reaction is the copper-catalyzed reaction between aryl halides
and aromatic amines or amides mediated yielding arylamines or arylamides,
respectively, in the presence of bases. The reaction is named after Irma
Goldberg who first described it in 1906.
Bucherer reaction:

Some phenols proceed reaction with aqueous ammonium nitrite to give

aromatic amines. The reactions are believed to take place via sulfite adduct of
the keto-tautomer of phenol. Similarly, certain aromatic amines can be
converted into phenols.
Balz–Schiemann reaction is the conversion of phenylamine (aniline)
into phenyl fluoride (fluorobenzene) using nitrous acid, fluoroboric
acid, and heat
 Mechanism of Balz Schiemann Reaction
the Balz–Schiemann reaction is thought to proceed via an SN1 reaction
mechanism, reactivity trends have been unpredictable. Aromatic amines
undergo diazotization under the influence of nitrous acid. Fluoroboric acid is
added to give rise to the corresponding aryl diazonium salt. This aryl diazonium
salt is subjected to heat to undergo thermal decomposition and give the aryl
fluoride along with nitrogen gas and boron trifluoride