Part 3
CHM1C3
Substitution Reactions
R1
R1
Nu
R1
Rate = k [R-Cl][Nu]
Nu
R3
2
R
Inversion
of
Configuration
Rate = k [R-Cl]
Nu
SN2
R3
2
R
Cl
R3
R2
R1
SN1
Nu
3
R
R2
Racemisation
of
Configuration
Content of Part 3
Part 3i.
The Role of Kinetics and Chirality in Determining
Mechanisms of the Substitution Reaction
Part 3ii.
Effect of Solvent on the Substitution Reaction
Part 3iii.
Effect of Structure on the Substitution Reaction
Part 3iv.
Nature of the Attacking Nucleophile
Part 3v.
Nature of the Leaving Group
Part 5i
Substitution Reactions:
Mechanisms
Bimolecular substitution (SN2) (and elimination (E2))
reactions and transition states
Unimolecular substitution (SN1) (and elimination (E1))
reactions and reactive intermediates
Content of Part 5i
The SN2 Reaction Mechanism
The SN1 Reaction Mechanism
Reaction Rates/Chirality in Determining the Mechanism
Transition States
Reactive Intermediates
CHM1C3
– Introduction to Chemical Reactivity of Organic
Compounds–
– Learning
Objectives Part 5i –
Substitution Reactions:
Mechanisms
After completing PART 4i of this course you should have an understanding of, and be able to demonstrate, the following
terms, ideas and methods.
(i)
Understand how by considering both the reaction kinetics and the stereochemical outcome of substitution
reactions the SN2 and SN1 mechanisms were devised,
(ii)
Understand the difference in timings of the arrow-pushing in the mechanisms of the SN2 and SN1 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.
Nucleophililic Substitution Reactions at sp3 Carbons
R
R
Stereochemistry
Rate
X
Nu
R'
Nu
Equation
R'
"R
X
"R
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
Clearly, two different reaction mechanisms must
be in operation.
It is the job of the chemists to fit the experimental
data to any proposed mechanism
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
SN2
The SN2 Reaction Mechanism
R
Nu
Bimolecular
Process
1
Nucleophile attacks from behind the
C-Cl s-bond.
Cl
R3
Rate = k[R-Hal][Nu]
2
R
sp3
This is where the s*-antibonding
orbital of the C-Cl bond is situated.
Rate
Determinig
Step
R1
1
–
2
Nu
Cl
R3
Bond
Forming
1
–
2
R2
Bond
Breaking
Transition State –
Energy Maxima
sp2
R1
Nu
R3
R2
Inversion
of Configuration
Cl
http://chemistry.boisestate.edu/rbanks/organic/sn2.gif
http://www.personal.psu.edu/faculty/t/h/the1/sn2.htm
http://www.bluffton.edu/~bergerd/classes/CEM221/sn-e/SN2-1.html
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.
involves partial bond cleavage and partial bond formation.
It
Transition States
Rate = k[A][B]
Transition
State
Energy
Maxima
E
n
e
r
g
y
See SN2 and E2
Reaction Mechanisms
[A.B]‡
DG‡
A+B
DGo
C+D
Reaction Coordinate
R1
1
–
2
Nu
Cl
R3
Bond
Forming
E
n
e
r
g
y
1
–
2
R2
Bond
Breaking
Transition State –
Energy Maxima
R
Nu
R3
sp2
1
Cl
2
R
R1
Nu
R3
2
R
Reaction Coordinate
Cl
SN1
The SN1 Reaction Mechanism
Unimolecular
Process
R1
Cl
R
3
R2
sp3
Rate = k[R-Hal]
Rate
Determining
State
Nucleophile attacks from either side
of the carbocationic intermediate.
R1
Nu
R3
R1
R2
Cl
Nu
R3
R1
R2
Reactive Intermediate –
Energy Minima
sp2
Nu
R3
R2
Racemisation
of
Configuration
Reactive Intermediates:
Mechanisms
See
SN1
and
E1
Reaction
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.
Reactive Intermediates
Rate = k[A]
Reactive
Intermediate
See SN1 and E1
Reaction Mechanisms
And Radical Chain
Reaction
C+B
EE
nn
ee
rr
gg
yy
DG‡
Energy
Minima DG‡
A+B
DGo
D+E
Reaction Coordinate
R1
R3
E
n
e
r
g
y
R1
Reactive Intermediate
R1
R3
R2
Nu
R3
2
Cl
R
2
R
R1
R3
Reaction Coordinate
Nu
R2
CHM1C3
– Introduction to Chemical Reactivity of Organic
Compounds–
– Summary
Sheet Part 3i –
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.
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, 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.
Exercise 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)
(ii)
Identify the product, and
propose an arrow pushing mechanism to account for the product formation.
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)
(ii)
Identify the product(s), and
propose an arrow pushing mechanism to account for the product formation.
Starting material molecular formula = C6H11Br
Me
Product molecular formula = C7H14S
Br
Lost Br, Gained SMe, Substitution Reaction
Rate equation indicates bimolecular process, SN2
Br
Me
Br
Me
Me
SMe
MeS
MeS
Envelope Conformation
of Cyclopentane
Me
SMe
Exercise 2: Substitution Reactions
Compounds A and B when treated with a weak base are deprotonated to form the carboxylate anion. One of these
carboxylate anions then reacts further to afford the lactone P, whilst the other carboxylate anion is does not lead to P.
Identify the carboxylate anion which affords P, and rationalise its formation with an arrow pushing mechanism, as well as
rationalising why the other carboxylate anion does not afford P.
I
HO
A
O
I
HO
B
O
O
P
O
Answer 2: Substitution Reactions
Compounds A and B when treated with a weak base are deprotonated to form the carboxylate anion. One of these
carboxylate anions then reacts further to afford the lactone P, whilst the other carboxylate anion is unaffected.
Identify the carboxylate anion which affords P, and rationalise its formation with an arrow pushing mechanism, as well as
rationalising why the other carboxylate anion does not afford P.
I
A
HO
B
I
O
HO
O
O
Base
Base
P Reaction must be
SN2 type, because if
O it was SN1 like the
carbocation
below
would be generated
from both S1 and S2.
Therefore both S1
and S2 would afford
P
I
O
O
I
s* orbital of C-I bond
O
O
H
HO
O