Chemistry

1. Substitution Reactions In
Aliphatic and Aromatic
Compounds
V
. Sri Krishna
A. Chakravarthy

2. Substitution Reactions-Definition
• Reactions which involve the replacement
or substitution of one or more atoms or
groups of a compound by other atoms or
groups are known as SUBSTITUTION
REACTIONS.

3. Classification
• Based on the nature of substituents involved:
A:Q + B·
A:Q + B-
1. Free Radical Substitution
A:B + Q·
2. Electrophilic Substitution
A:B + Q-
3. Nucleophilic Substitution
A:B + Q+ A:Q + B+

4. Free Radical Substitution
• Radical substitution reactions are initiated by
radicals in the gas phase or in non-polar
solvents.
• For example, methane and chlorine react in
presence of sunlight or heat to give
methylchloride

5. Mechanism of free radical substitution
• Light energy or heat causes homolytic fission of
chlorine producing chlorine radicals which attack
methane to form methylchloride.

6. Termination by formation of stable molecules:
• When the ratio of methane to chlorine is high,
methylchloride is formed predominantly.
• When chlorine is in excess, all hydrogens are
replaced to give carbon tetrachloride.

7. Electrophilic Substitution
• When the substitution involves attack by an
electrophile, it is electrophilic substitution.
• This occurs in both aliphatic and aromatic
compounds and hence classified as:
• Electrophilic Aliphatic Substitution
• Electrophilic Aromatic Substitution

8. Electrophilic Aliphatic Substitution
• This reaction is similar to Nucleophilic
Substitution reaction and are differentiated
based on their mechanisms as SE1 and SE2
• Examples:
Nitrosation
Ketone halogenation
Keto-enol tautomerism
Aliphatic diazonium coupling
Carbene insertion into C-H bonds

9. Electrophilic Aromatic Substitution
• A = Electrophile
• B = Lewis Base

10. Examples
• Nitration:
• Sulphonation:
• Halogenation:

11. Examples
• Friedel-Craft’s alkylation:
• Friedel-Craft’s acylation:

12. Effect of Substituents
• Any substituents, if present, affect both the
regioselectivity and speed of the reaction.
• In terms of regioselectivity, the substituents
may be ortho-para directing or meta directing.
• In terms of kinetics, substituents may increase
(activating) or decrease (deactivating) the rate
of reaction.

13. Activating
Substituents:
• They stabilize the
cationic intermediate
formed during the
substitution by donating
electrons into the ring
system, by either
inductive effect or
resonance effects.
Examples are toluene,
aniline and phenol
Deactivating
Substituents:
• These destabilize the
intermediate cation and
thus decrease the
reaction rate by
withdrawing electron
density from the
aromatic ring.
Examples are nitrobenzene,
benzaldehyde and
trifluoromethylbenzene

14. Ortho/para directors
Ortho substitution

15. Ortho/para directors
Para substitution

16. Ortho/para directors
Meta substitution

17. • Non-halogen groups with atoms that are more
electronegative than carbon, such as a carboxylic acid
group (CO2H) draw substantial electron density from
the pi system.
• These groups are strongly deactivating groups.
• Additionally, since the substituted carbon is already
electron-poor, the resonance contributor with a
positive charge on this carbon (produced by ortho/para
attack) is less stable than the others.
• Therefore, these electron-withdrawing groups are
meta directing
Meta directors

18. Nucleophilic Substitution
• Nucleophilic substitution involves the
displacement of a nucleophile by
another.
• Nucleophilic substitution may be any one
of the following:
– Nucleophilic aliphatic substitution
– Nucleophilic aromatic substitution

19. Aliphatic Nucleophilic substitution
• In 1935, Edward D. Hughes and Sir Christopher
Ingold studied nucleophilic substitution reactions of
alkyl halides and related compounds.
• They proposed two main mechanisms—
the SN1 reaction and the SN2 reaction.
• S stands for chemical substitution, N stands for
nucleophilic, and the number represents the kinetic
order of the reaction.

20. SN1 Reaction Mechanism
• L = Leaving group
• Nu- = Attacking Nucleophile

21. SN2 Reaction Mechanism
• L = Leaving group
• Nu- = Attacking Nucleophile

22. Factor SN1 SN2
Kinetics Rate = k[RX] Rate = k[RX][Nuc]
Primary alkyl Never Good
Secondary alkyl Moderate Moderate
Tertiary alkyl Excellent Never
Leaving group Less Basic Less Basic
Nucleophilicity Unimportant Important
Preferred Solvent Polar protic Polar aprotic
Stereochemistry Racemisation(more inversion
possible)
Walden Inversion
Rearrangements Common Rare
Eliminations Common, especially with basic
nucleophiles
Only with heat and basic
nucleophiles

23. Examples
• Organic reductions with hydrides, for example
R-X → R-H using LiAlH4 (SN2)
• Hydrolysis reactions such as
R-Br + OH− → R-OH + Br− (SN2) or
(SN1)
R-Br + H2O → R-OH + HBr
• Williamson ether synthesis
R-Br + OR'− → R-OR' + Br− (SN2)
• The Wenker synthesis, a ring-closing reaction of
aminoalcohols.
• The Finkelstein reaction, a halide exchange reaction
• The Kolbe nitrile synthesis, the reaction of alkyl halides
with cyanides.

24. Aromatic Nucleophilic substitution
• A nucleophilic aromatic substitution is a
substitution reaction in which the nucleophile
displaces a good leaving group,on an aromatic
ring.
There are 6 nucleophilic substitution mechanisms encountered with aromatic systems.

25. SNAr (addition-elimination) mechanism

26. The aromatic SN1 mechanism
encountered with diazonium salts

27. The benzyne mechanism

28. Radical-nucleophilic aromatic
substitution

29. ANRORC mechanism
ANRORC stands for Addition of the Nucleophile, Ring Opening, and Ring
Closure in nucleophilic attack on ring systems

30. Vicarious nucleophilic substitution

31. Examples
• In the Bamberger rearrangement N-
phenylhydroxylamines rearrange to 4-
aminophenols. The nucleophile is water.
• In the Sandmeyer reaction and the
Gattermann reaction diazonium salts react
with halides.
• The Smiles rearrangement is the
intramolecular version of this reaction type.

32. References
• Reactions, Rearrangements and Reagents by
S.N.Sanyal
• Reactions and Reagents by O.P.Agarwal
• www.wikipedia.org
• Google Images

33. Thank
You