ALIPHATIC NUCLEOPHILIC
SUBSTITUTION REACTION
NUCLEOPHILIC &
ELECTROPHILIC
SUBSTITUTION REACTION
IN ALIPHATIC &
AROMATIC SYSTEM • The carbon must be SP3 hybridized.
By Syeda Kiran Ijaz
EXAMPLE
□ Substitution reaction involve bond making & bond breaking steps.
□ C-nuceophile bond formed, C-leaving group bond break.
Example: Reaction of sodium cyanide with alkyl chloride
Breaking
Condition:
of C-Cl
• For the nucleophilic substitution, the tetrahedral carbon should have bond &
at least some partial positive charge on it. sodium formation
cyanide of C-C
• The electrophilic carbon is attached to halogen (e with drawing) such Alkyl chloride Alkyl cyanide
bond
compounds are called as alkyl halides. C N
ambident ion
ENERGY DIAGRAM FOR
MECHANISM B
N • Mechanism B: 2 steps
C is • Step 1: Formation of carbocation / bond breaking
tetra
valent • Step 2: Attack of nucleophile / bond making
carbocation
C
Rate determining Fast step
N step Breaking bond cost
-NaCl slowest step energy
too much energy making bond realease
transition state energy
need to break C-
Cl b d
• Some energy added to break the C-Cl bond
• Chlorine leave the molecule (leaving group) Bond
• Carbocation is formed breaking
• Ion pair (carbocation & anion) is an intermediate
• Nucleophile ( CN) attack the carbocation i-e C-Cbond formation
carbocation
Bond
making
Summary:
• 2 steps
1st step : bond breaking
Cl leave the 2nd step : bond making
molecule • 1st step is rate determining
ENERGY DIAGRAM FOR
MECHANISM C
RATE LAW FOR MECHANISM B • Mechanism C :
• The rate law for the step wise mechanism is;
RATE = K [REACTANT]
• Rate depends on the 1 st elementary step.
• Order of reaction : First-order
• A first-order reaction is a chemical reaction in which the reaction rate is
dependent on the concentration of only one reactant. Rate determining step
• According to Ingold, reactions that follow first order , or the rate of transition state
reaction depends only on the concentration of only one reactant are
categorize as SN1 reactions.
Short time, • Summary:
transition • 1 step mechanism
state
High energy, • C-C bond formation & C-Cl bond breaking occur at same time as a
single step.
more
unstable • Nucleophile displaces chlorine directly in one step.
• There is formation of transition state.
H
TYPES OF ALIPHATIC
RATE LAW FOR MECHANISM C NUCLEOPHILIC SUBSTITUTION
According to the rate law described by C.K. REACTION
• The rate law for this concerted mechanism is; •ingold
Two types
RATE = K [REACTANT][NUCLEOPHILE] 1. Sn1 For
• Order of reaction: 2nd order 2. Sn2 reactions &
• A second order reaction is chemical reaction in which the rate of the
mechanism
reaction is dependent on both the concentration of the nucleophile see
3. SN1 ; UNIMOLECULAR SUBSTITUTION REACTION
and that of the reactant. previous
• Rate of reaction depends on only one reactant
• According to Ingold, reactions that follow second order , or the rate of slides under
reaction depends on the concentration of reactant & nucleophile are • Rate of reaction:
the title
categorize as SN2 reactions. RATE = K[REACTANT]
organic
• Order of reaction : first order reactions.
• Two step reaction
B d ki &b db ki i 2 diff
ALIPHATIC ELECTROPHILIC
1. SN2 ; BIMOLECULAR SUBSTITUTION REACTION SUBSTITUTION REACTION
• Rate of reaction depends on reactant & nucleophile For reactions
• Rate of reaction: & mechanism
RATE = K[REACTANT] [NUCLEOPHILE] see previous
• Order of reaction : first order slides under
the title
• One step reaction organic
• Bond making & bond breaking occur in one single step reactions.
ALIPHATIC ELECTROPHILIC
EXAMPLE
SUBSTITUTION REACTION
Chlorination of
• Chemical reactions where an electrophile (atom/molecule/ion which
acetone:
are e- deficient) displace a functional group or an atom in a compound.
• Related to carbanion.
• Electron pair of the breaking bond remain with the substrate to form Cl Cl
bond with the coming electrophile.
acetone chlorine chloroacetone
e rich species
following diff
pathways
SE1(UNI MOLECULAR
TYPES OF ELECTROPHILIC
ELECTROPHILIC SUBSTITUTION
SUBSTITUTION REACTION REACTION)
1. Uni molecular electrophilic substitution reaction / SE1
2. Bi molecular electrophilic substitution reaction / SE2
Further classified as;
a. SE2 front
b. SE2 back
• Difference is the intermediate formed.
In SN1 , intermediate formed is carbocation & in SE1 the intermediate formed is
carbanion
GENERAL REACTION REACTION MECHANISM
• Similar to SN1 reactions.
• Involves two steps.
❑ Step # 1: Slow heterolysis / ionization , formation of carbanion (RD
step) slow
Leaving
group
R X
Intermediate/ R + X
carbanion
❑ Step # 2: electrophilic attack / combination of attacking electrophile
with carbanion
Step # 1: Slow heterolysis / ionization , formation of
carbanion
• Rate of reaction:
RATE = K [REACTANT]
Step # 2: electrophilic For reactions
Order of reaction:
attack & mechanism
first order see previous
slides under
the title
organic
reactions.
EXAMPLES OF SE1 REACTION
• Decarboxylation of aliphatic acid
• Acid/base catalysed Halogenation of aldehydes / ketones
STEP 1
bromo acetone
enolate
enolate
acetone can accept a proton (H+)
from another substance
SE2(BI MOLECULAR
ELECTROPHILIC SUBSTITUTION GENERAL REACTION
REACTION)
SE2 backside rxn
SE2 front side rxn
For reactions
AROMATIC ELECTROPHILIC &
& mechanism MECHANISM NUCLEOPHILIC SUBSTITUTION
see previous
slides under REACTIONS
the title
S
• Electrophilic Aromatic Substitution is the reaction in which an
organic RD electrophile substitutes hydrogen in the aromatic ring.
reactions.
• Nucleophilic Aromatic Substitution is the reaction in which a
nucleophile substitutes a leaving group in the aromatic ring.
• Aromatic compounds are chemical compounds that consist of
conjugated planar ring systems accompanied by delocalized pi-
electron clouds in place of individual alternating double and single
bonds.
RD
S
• They are also called aromatics or arenes.
• Aromatic compounds are broadly divided into two categories:
benzenoids (one containing benzene ring) and non-benzenoids (those
not containing a benzene ring) for example, furan , thiophene & pyrrole.
AROMATIC NUCLEOPHILIC
SUBSTITUTION REACTION
Non- benzenoids aromatic ARSN
compounds
• Definition: substitution reaction in which a nucleophile substitutes a
leaving group (typically H) in the aromatic ring.
• Aromatic nucleophilic substitution reactions are often considered
difficult.
• WHY??
furan thiophene
pyrrole.
2. Aromatic Stability:
1. Electron Density Distribution: Aromatic rings have a unique
distribution of electron density, with pi electrons delocalized over the L
entire ring.
reaction
L = electron
not
Nu rich species /
possible
positive
Different
inductive
conjugating
effect
structures,
(electron
L makes the
donating)
aromatic
group
compound
more stable
Another Factors for low reactivity of aroamtic
parti nucleophilic substitution reaction is ;
al
• presence of electron cloud on the aromatic ring
This shield the ring from the attack of nucleophile.
POSSIBILITY
If more
electronegative
atom (halogens)
or groups
showing negative
inductive effect (
electron
withdrawing )
group is attached
to aromatic ring
AROMATIC SUBSTITUTION
TYPES OF AROMATIC NUCLEOPHILIC UNIMOLECULAR
NUCLEOPHILIC SUBSTITUTION REACTION
• ArSN1:
1. ArSN1
2. ArSN2
3. Aromatic nucleophilic substitution via benzyne / aryne
Diazonium aryl cation
salt
AROMATIC SUBSTITUTION
EXAMPLES NUCLEOPHILIC BIMOLECULAR
Nucleophil REACTION
e • ArSN2: most common
Reactant
aromatic azide
Diazonium
salt CH3OH OCH3 + H+
ARENIUM ION /Wheland intermediate /
cyclohexadienyl cation
IPSO ADDITION
• A position which is already occupied by a non-hydrogen
substituent in an aromatic ring is called. ipso position .
• (Latin: ipso, on itself), the attack on this position is called
ipso attack (or ipso addition), and the aromatic substitution
in which a substituent already present is replaced is called
ipso. substitution.
MECHANISM
IPSO
addition
intermediate anion
FACTORS EFFECTING REACTIVITY OF AROMATIC NUCLEOPHILIC
SUBSTRATE FOR ARSN2 REACTION SUBSTITUTION VIA BENZYNE / ARYNE
• This reaction proceeds via benzyne (aryne) intermediate and the
mechanism is called benzyne (aryne) mechanism.
• An interesting feature of this reaction is that the incoming nucleophile
does not necessarily take the position vacated by the leaving group.
• This is called cine substitution.
• Cine is from greek word meaning movement.
• The mechanism of this reaction involve Elimination followed by
Addition , so the reaction is also called ase elimination-addition
mecahnism of aromatic nucleophilic substitution
• Unactivated aryl halide:
• In organic chemistry, "activation" typically refers to the
introduction of electron-donating or electron-withdrawing
groups on the aromatic ring, which can influence the reactivity
of the compound.
NH2 = H
nucleophile
• Unactivated aryl halides are often less reactive in various
chemical reactions compared to their activated counterparts.
This is because the electron density in the benzene ring of
unactivated aryl halides is not significantly altered by X
additional substituents, making them less prone to nucleophilic
substitution reactions .
• "unactivated" aryl halide is one where the halogen has less
impact on the reactivity of the aromatic ring, and the reaction
usually proceeds at a slower rate or with different selectivity
compared to activated aryl halides
REACTION • Cholorbanzene on treatment with potassium amide in liquid ammonia
give almost equal amount of 1-14 C aniline and 2-14 C aniline.
• The formation of these two products depends on the attack of
ammonia (nucleophile) on either of two positions on the intermediate
formed.
NH2
H2
-KCl
FACTORS
PREDICTION OF MAJOR PRODUCT IN
REACTION PROCEEDING VIA ARYNE • One can predict the major product among these product mixture.
• Two factors govern the position of the incoming group in a reaction
1. Incase of ortho/para substituted halobanzene two products are possible. involving benzyne intermediate.
X
X
1) Direction in which benzyne is formed:
2 PRODUCTS Condition 1: o/p substituted halobanzene, there is no choice.
H
2. Incase of meta substituted halobanzene three products are possible.
H H
X X
• In such cases (meta substitued) the more acidic hydrogen is removed.
Condition2: meta substituted halobanzene, there is choice of formation of
two different types of benzynes.
Q. Which hydrogen is more acidic?
Ans.
H
□ If the G group is electron withdrawing (-I) then Hydrogen ortho to it
will be more acidic and will be removed.
□ If G is electron donating (+ I) then Hydrogen para to it will be more
H acidic and will be removed.
EXAMPLE
A B
G is electron G is electron donating ,
withdrawing , then then para H will be
ortho H will be removed and product
removed and product B will be the major
A will be the major product
product
AROMATIC ELECTROPHILIC
SUBSTITUTION REACTIONS
• In electrophilic aromatic substitution a C-H bond is broken and a new
• Characteristic reaction as are very common reactions in aromatic compounds. C-E bond (E being an electrophilic atom such as Cl, Br, N…) is formed.
• There is cloud of pi electrons above and below the aromatic ring that are loosely
held as compared to sigma electrons and are available to electron deficient
species i-e electrophile.
• There is formation of an intermediate known as arenium ion intermediate.
• There are six key electrophilic aromatic substitution reactions: chlorination,
bromination, nitration, sulfonation, Friedel-Crafts alkylation, and Friedel-Crafts
acylation.
• Each of these reactions requires an acid catalyst to activate it so that the
relatively unreactive aromatic ring will attack it.
LEWIS ACIDS ACCELERATE THE RATE
OF ELECTROPHILIC AROMATIC ARENIUM ION FORMATION
SUBSTITUTION REACTIONS
protonation
of banzene
Benzenium ion
STABILITY OF ARENIUM ION DEFINITION OF ARENIUM ION
Cholorination:
Step 2
chlorobanzene
ENERGY LEVEL DIAGRAM
SUMMARY
