The document discusses nucleophilic substitution reactions (SN1, SN2, SNi) at sp3 carbons. It explains the key differences between the SN1, SN2 and SNi mechanisms based on their rate equations, stereochemical outcomes, and whether they proceed through a bimolecular transition state (SN2) or a unimolecular carbocation intermediate (SN1). Transition states and reactive intermediates are described. Factors that affect the relative rates of the SN1 and SN2 mechanisms are also discussed, including the nature of the substrate, nucleophile and leaving group, as well as solvent effects.

1. Nuecleophilic
Substitution Reactions
Gautam Sadawarte
Department of Chemistry
B.P. Arts, S.M.A. Science,
K.K.C. Commerce College
Chalisgaon

2. Nuecleophilic
Substitution Reactions
R1
R2
R3
Cl
Nu
R1
R2
R3
Nu
Inversion
of
Configuration
Racemisation
of
Configuration
R1
R2
R3
Nu
R1
R2
R3
Nu
Rate = k [R-Cl][Nu]
SN2
Rate = k [R-Cl]
SN1

3. (i) Understand how by considering both the reaction kinetics and the stereochemical outcome
of substitution reactions the SN2, SN1 and SNi mechanisms were devised,
(ii) Understand the difference in timings of the arrow-pushing in the mechanisms of the SN2, SN1
and SNi reaction,
(iii) Understand the terms bimolecular and unimolecular,
(iv) Understand the reaction energy profile for a reaction in which a transition state leads to the
formation of the products – a SN2 reaction, and
(vi) Understand the reaction energy profile for a reaction in which a reactive intermediate leads to
the formation of the products – a SN1 reaction.
(vii) Understand the reaction mechanism and intermediate leads to the formation of the products
in a SNi reaction.
Substitution Reactions:
Mechanisms
– Introduction to Chemical Reactivity of Organic
Compounds–

4. Nucleophililic Substitution Reactions at sp3 Carbons
It is found that there are two possible stereochemical outcomes, each described
by a different rate equation, and different stereochemical outcomes.
Descriptor Rate Equation Stereochemical
Outcome
SN2 rate = k[R-Hal][Nu] Inversion
SN1 rate = k[R-Hal] Racemisation
Stereochemistry
Rate
Equation
Nu
R
R'
"R
X
X
R
R'
"R
Nu

5. Reaction Mechanisms
The mechanism of a reaction consists of everything that happens as the
starting materials are converted into products.
In principle, therefore, writing (or drawing) the mechanism means describing
everything that happens in the course of the reaction.
However, providing an exact description of a reaction on paper is an
impossible goal.
Instead, a proposal for the mechanism of a reaction should include certain
types of information about the course of the reaction. Thus, the reaction
mechanism should:
[1] Account for the number of reaction steps as indicated by the
rate equation
[2] Account for reactive intermediates or transition states
[3] Account for any stereochemical relationships between
starting materials and products

6. SN2

7. The SN2 Reaction Mechanism
Cl
R1
R3
R2
Nu
Transition State –
Energy Maxima
Bond
Forming
2
1
–
2
1
–
sp2
Bond
Breaking
R1
R2
R3
Nu Cl
Inversion
of Configuration
Nucleophile attacks from behind the
C-Cl s-bond.
This is where the s*-antibonding
orbital of the C-Cl bond is situated.
Rate = k[R-Hal][Nu]
R
1
R
2
R3
Cl
Nu
sp3
Bimolecular
Process
Rate
Determinig
Step

8. http://chemistry.boisestate.edu/rbanks/organic/sn2.gif

9. http://www.personal.psu.edu/faculty/t/h/the1/sn2.htm

10. http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2-1.html

11. Transition States: See SN2 and E2 Reaction Mechanisms
A transition state is the point of highest energy in a reaction or in
each step of a reaction involving more than one step.
The nature of the transition state will determine whether the reaction
is a difficult one, requiring a high activation enthalpy (DG‡), or an easy
one.
Transition states are always energy maxima, I.e. at the top of the
energy hill, and therefore, can never be isolated.
A transition states structure is difficult to identify accurately. It
involves partial bond cleavage and partial bond formation.

12. Transition States
A + B
E
n
e
r
g
y
Reaction Coordinate
A + B
C + D
[A.
B]‡
Transition
State
Energy
Maxima
Rate = k[A][B]
See SN2 and E2
Reaction Mechanisms
DG‡
DGo

13. E
n
e
r
g
y
Reaction Coordinate
R1
R2
R3
Cl
Nu
R1
R2
R3
Nu Cl
Cl
R1
R3
R2
Nu
Transition State –
Energy Maxima
Bond
Forming
2
1
–
2
1
–
sp2
Bond
Breaking

14. SN1

15. The SN1 Reaction Mechanism
R1
R2
R3
Nu
R1
R2
R3
Nu
Racemisation
of
Configuration
R1
R2
R3
Cl
sp3
Unimolecular
Process
Rate = k[R-Hal]
Rate
Determining
State
R1
R3
R2
Nu Cl
Reactive Intermediate –
Energy Minima
sp2
Nucleophile attacks from either side
of the carbocationic intermediate.
R1
R3 R2
+ Cl-

16. Reactive Intermediates: See SN1 and E1 Reaction
Mechanisms
Reactive intermediates are energy minima, i.e. at the bottom of the energy hill,
and therefore, can be isolated.
A reactive intermediate structure is much easier to identify and in certain cases
these high energy species can be isolated and structurally characterised.

17. DGo
E
n
e
r
g
y
DG‡ DG‡
E
n
e
r
g
y
Reaction Coordinate
A + B
D + E
C + B
Reactive
Intermediate
Energy
Minima
Reactive Intermediates
Rate = k[A]
See SN1 and E1
Reaction Mechanisms
And Radical Chain
Reaction

18. E
n
e
r
g
y
Reaction Coordinate
R1
R2
R3
Cl
R1
R3
R2
R1
R2
R3
Nu
R1
R2
R3
Nu
Reactive Intermediate

19. – Summary–
Substitution Reactions:
Mechanisms
The difference in electronegativity between the carbon and chlorine atoms in the C-Cl sigma (s)
bond result in a polarised bond, such that there is a partial positive charge (+) on the carbon atom and a slight
negative charge (-) on the halogen atom. Thus, we can consider the carbon atom to be electron deficient, and
therefore electrophilic in nature (i.e. electron liking). Thus, if we react haloalkanes with nucleophiles
(chemical species which have polarisable lone pairs of electrons, which attack electrophilic species), the
nucleophile will substitute the halogen atom.
which in turn is transmitted to the -carbon atom and the protons associated with it. Thus, the
hydrogen atoms on the -carbon atom are slightly acidic. Thus, if we react haloalkanes with bases (chemical
species which react with acids), the base will abstract the proton atom, leading to carbon-carbon double bond
being formed with cleavage of the C-Cl bond.
Substitution (and elimination) reactions can be described by two extreme types of mechanism. One
mechanism is a concerted and relies on the starting materials interacting to form a transition state, and the
other is a step-wise process in which one of the starting material s is converted into a reactive intermediate,
which then reacts with the other reagent.
Discussions of transition states and reactive intermediates in the course of a reaction is very useful
when proposing an organic reaction mechanism, which takes into account the experimental evidence for a
reaction, such as rate equations and stereochemical outcomes.
– Introduction to Chemical Reactivity of Organic
Compounds–

20. SNi
OH
H3C
H
Ph
+ SOCl2
H3C
H
Ph
S
O
Cl
O
+ + HCl

21. The SNi Reaction Mechanism
Nucleophile (Cl-) generate and
attack from Same side
OH
H3C
H
Ph
+ SOCl2 O
H3C
H
Ph
S
Cl
O
+ HCl
O
H3C
H
Ph
S
Cl
O
O
H3C
H
Ph
S
O
Cl-
+
H3C
H
Ph
Cl
S
O
O
+
Retaintion in Configuration

22. The SNi Reaction PY
generate and Cl-
attack from Back side
OH
H3C
H
Ph
+ SOCl2 O
H3C
H
Ph
S
Cl
O
+ HCl
Inversion in Configuration
N
+ HCl
N
H+
Cl-
O
H3C
H
Ph
S
Cl
O
Cl-
H3C
H
S
O
O
Ph
Cl + + Cl-

23. NGP
Nuecleophilic attack
takes place Same side
Retenation in Configuration
Et
O
Et
H
Br
CH3
Et
Et
O H
CH3
OH
Hydrolysis
Neighbouring Group Participation
O,S,N Having
LP electron
Mechanisum
Et
O
Et
H
Br
CH3
Et
Et
O H
CH3
+ Br
Et
Et
O H
CH3
OH
Et
Et
O H
CH3
OH

24. NGP Neighbouring Group Participation
C
H2
Et S H2
C
Cl
Et S
C
H2
CH2
H2O
Fast
C
H2
Et S H2
C
OH

25. NGP Norbornyl System
The π orbitals of
an alkene can
stabilize a by
delocalize the
positive charge
of the
carbocation
unsaturated tosylate
will react more
quickly (1011 times
faster for aqueous
solvolysis) with a
nucleophile than the
saturated tosylate

26. Exercise NGP
Alkyl benzenesulfonate the alkene is able to
delocalise the carbocation.

27. Answer 1: Substitution Reactions
cis-1-Bromo, 3-methylcyclopentane reacts with NaSMe (MeS— is an excellent nucleophile) to afford a product with
molecular formulae C7H14S. The rate of the reaction was found to be dependent on both the bromoalkane and the NaSMe.
(i) Identify the product(s), and
(ii) propose an arrow pushing mechanism to account for the product formation.
Br
Me
Me Br
MeS
Me
Br
MeS
Me
SMe
SMe
Me
Starting material molecular formula = C6H11Br
Product molecular formula = C7H14S
Lost Br, Gained SMe, Substitution Reaction
Rate equation indicates bimolecular process, SN2
Envelope Conformation
of Cyclopentane

28. Factor affecting on SN1 & SN2
Nature of Substrate
SN2 mechanism concerted and attack of Nuecleophilic
takes places backside as in primary alkyl halide hydrogen
are smaller group which increases rate of reaction
SN2
While tertiary alkyl halide conation bulky group which
increases steric hindrance hence attack of nu prohibited
and rate of reaction decreases
Methyl > Primary > Secondary > Tertiary

29. Factor affecting on SN1 & SN2
Nature of Substrate
SN1 mechanism involve Formation of cabocation in RDS.
SN1
In tertiary alkyl halide conation alkyl group which
increases electron density on cabocation which cabocation
hence rate of reaction increases
While in primary alkyl halide rate of reaction decreases
Methyl < Primary < Secondary< Tertiary
H
H
H
H
CH3
H
H3C
CH3
H
H3C
CH3
CH3

30. Factor affecting on SN1 & SN2
Nature of Substrate
Compound Relative SN1 Rate Relative SN2 Rate
Methyl halide 30 1.5
Ethyl Halide 1.0 1.0
Isopropyl Halide 0.002 12
Tertiary Butyl
Halide
0 1200000

31. Factor affecting on SN1 & SN2
Benzylic Substrate
CH2
CH2
Cl
CH2
Hydrolysis
CH2
OH
H2C
H2C H2C H2C
Benzyl Halides are very much
reactive in SN1 Reaction
Because Carbonation Stabilized
by resonance

32. Factor affecting on SN1 & SN2
Benzylic Substrate
Compound Relative SN1 Rate
CH3 CH2 -X 1.0
C6H5 CH2 -X 380
(C6H5)2CH -X 100000

33. Factor affecting on SN1 & SN2
Allylic Substrate
H2C
C
H
H2
C
Cl
H2C
C
H
H2
C
Cl
H2C
C
H
CH2 H2C
C
H
CH2
H2O
H2C
C
H
H2
C
OH
Allylic carbcation stabilised
By resonance
TS have low energy
hence SN1 reaction faster

34. Factor affecting on SN1 & SN2
Bridged Carbon
H
C
H2C
H2C
C
H
CH2
CH2
H2C
Bycyclo-alkane
carbon atom common to the both ring
Br
1
Br
10-14
Br
10-14
Br
10-16
SN1 & SN2
Reaction
not possible
Forbidden

35. Factor affecting on SN1 & SN2
Nature of Nucleophile RDS in SN1 no
involvement of
Nu
While in SN2 Nucleophile
play important role in RDS
R1
R2
R3
Cl
sp3
Unimolecular
Process
Rate = k[R-Hal]
Rate
Determining
State
Rate = k.[R-Hal][Nu]
bimolecular
R
1
R
2
R3
Cl
Nu
sp3
Strong nu reacts rapidly
Poor nu reacts slowly

36. Factor affecting on SN1 & SN2
Nature of Nucleophile
OH H
O
H
> >
R
O
R
O
H
R
O
OH R
COO
R
O
H H
O
H
> >> > >
I Br Cl
> > >
RS RO
Negatively Charged Nucleophile
stronger than Conjugate acid
As size of atom increases nucleophilicity also increases

37. Factor affecting on SN1 & SN2
Nature of Leaving group
1) Strength of R-X 2) Polarisation of R-X bond
3) Stability of X - 4) Salvation of X – at TS
In RDS of SN1 & SN2 – Nature of leaving play
important role
R1
R2
R3
Cl
sp3
Unimolecular
Process
Rate = k[R-Hal]
Rate
Determining
State
R
1
R
2
R3
Cl
Nu
sp3

38. Factor affecting on SN1 & SN2
Nature of Leaving group
R-I > R-Br > R-Cl > R-F
Iodine is better leaveing group than bromine
Poor leaving group converted into better leaving group
Better leaving group increases rate of reaction in both
SN1 & SN2
R S
O
O
O
Alkane Sulphonate ion
O S
O
O
O
R
Alkyl Sulphonate ion

39. Factor affecting on SN1 & SN2
Nature of Leaving group
R Cl + H2O R OH + HCl
R Cl + I R I
R I H2O R OH + HI
+
R OH + Br not takes place or slowly
R OH + H R OH2
Br
R Br

40. Factor affecting on SN1 & SN2
Nature of Leaving group
S
O
O
O
H3C
tosylate. 4-Methylbenzenesulfonate
S
O
O
O
O2N
nosylate (methyl 4-nitrobenzenesulfonate)
S
O
O
O
Br
brosyla te (or para-bromophenylsulfonyl)
O S
O
O
O
R
Alkyl Sulphonate ion

41. Effect of sovent
Polar protic solvent makes nucleophile less nucleophilic and
stabilizes anionic leaving group
Polar solvent stabilizes transition state and carbocation
intermediate.
SN2
Need polar solvent to dissolve nucleophile.
SN1
Aprotic solvent increases rate by binding cation and
thus freeing nucleophile.
Protic solvent slows rate by solvating nucleophile