Nature Of Substrate Nature Of Nucleophile Nature of Solvent Nature Of Leaving Group

1. Factors Affecting Nucleophilic
Substitution Reactions
By Sumaiya Banu S.Y.B.Pharmacy

2. Four Factors…..
1. Nature Of Substrate
2. Nature Of Entering Group a.k.a. Nucleophile
3. Nature of Solvent
4. Nature Of Leaving Group

3. SN1 and SN2 Reactions

4. Nature of Substrate
SN1(stability)
• As there is formation of Carbocation in the SN1 mechanism; more stable
the Carbocation more reasonable the SN1 reaction rate
• tertiary > secondary >> (primary—unreactive)
• Only tertiary halides react by an SN1 mechanism(moststable).
SN2(steric hinderance)
• Simple alkyl halides show the following general order of reactivityin SN2
reactions:
Methyl > primary > secondary >> (tertiary—unreactive)
• The important factor behind this order of reactivity is a steric effect,
and in this case, steric hindrance.

5. • Very large and bulky groups can often hinder the formation of the required transitionstate. In some cases
they can prevent its formation altogether.
• Tertiary carbocations are stabilized because sigma bonds at three adjacent carbons contribute
electron density to the carbocation p orbital by hyperconjugation. Secondary and primary
carbocations have less stabilization by hyperconjugation. A methyl carbocation has no
stabilization.

6. Nature Of Entering Group a.k.a. Nucleophile
• Nucleophile: Donate a lone pair of electron
• Basicity: nucleophile attackshydrogen
• Nucleophilicity: nucleophile attacksany atom other than hydrogen
• Nucleophilicity is measured by relative rates of reaction,by how rapidly an
electron pair donor reacts at an atom (usually carbon) bearing a leaving
group.
• Nucleophile does not participate in the rate-determining step of an SN1
reaction, the rates of SN1 reactions are unaffected by either the
concentration or the identity of the nucleophile
• The rates of SN2 reactions, however, depend on both the
concentration and the identity of the attackingnucleophile.

7. FACTORS
• Nucleophile should be small in size.
• Nucleophile should less electronegative.
• Nucleophile should be strong Base.
• A good nucleophile is one that reacts rapidly in an SN2 reaction with a
given substrate [STRONGER BASES]. A poor nucleophile is one that
reacts slowly in an SN2 reaction with the same substrate under
comparable reaction conditions [WEAK BASES].

8. • Methanol, on the other hand, is a poor nucleophile for reaction with
iodomethane. Under comparable conditions it reacts very slowly. It is
not a sufficiently powerful Lewis base (i.e., nucleophile) to cause
displacement of the iodide leaving group at a significant rate:
• Methoxide anion, for example, is a good nucleophile for a
substitution reaction with iodomethane. It reacts rapidly by an SN2
mechanism to form dimethyl ether:

9. Nature of Solvent
• Two Types of solvents
Polar Non-Polar
Polar Protic Polar Aprotic
• SN2 SN1
• Can donate H+ ions Cannot donateH+ ions
• Solvateboth anionand cation Solvateonly Cation
• Eg.: CH3COOH, R-NH2,etc Eg.: DMF, DMSO, HMPT,
Acteone,etc

10. SN1 and SN2 Reactions

11. Two properties affecting rate of reaction:
• Ionization Power
Dielectrict constant SN1 Highly Polar
Polarity SN2 Less Polar
Ionization Power
• Solvation Power

12. Nature of Leaving Group
• Weaker the base stronger the leaving group
• In either an SN1 or SN2 reaction the leaving group begins to acquire a
negative charge as the transition state is reached.
• If it were a strong base it will put +ve charge on C atom, which is
undesired.
• This lowers the free energy of activation and thereby increases the
rate of the reaction.
• Weaker the bond b/w C and the leaving group, more easy will it be to
carry out SN1 and SN2 reaction

13. • The hydroxideion, for example, is a strong base and thus
reactionslike the following do not take place:
• However, when an alcoholis dissolved in a strong acid, it
can undergo substitutionby a nucleophile.Because the acid
protonatesthe -OH group of the alcohol,the leavinggroup
no longer needs to be a hydroxideion;it is now a molecule
of water—a much weaker base than a hydroxideion and a
good leavinggroup:

14. • Among the halogens, an iodide ion is the best leaving group and a
fluoride ion is the poorest:
• The trifluoromethanesulfonate ion (CF3SO3
-, commonly called the triflate
ion) is one of the best leaving groups known to chemists.

15. Thank you