Chapter 2 Energetics, Kinetics, and The Investigation of Mechanism

2.
Energetics, kinetics, and investigation of mechanism
2.1 Energetics of Reaction

2.2 Kinetics of Reaction
2.2.1 Reaction Rate and Free Energy of Activation
2.2.2 Kinetics and the Rate-Limiting
Rate Limiting Step
2.2.3 Kinetic vs Thermodynamic Control
2 3 Investigation of Reaction Mechanisms

2.3
2.3.1 The Nature of the Products
2.3.2 Kinetic Data
2.3.3 The Use of Isotopes
2.3.4 The Study of Intermediates
2.3.5 Stereochemical Criteria
2. Energetics, kinetics, and investigation of mechanism
“How far” will the reaction go over towards products?
Systems tend to move towards their most stable state.
G o  H o  TS o
G o   RT ln K
 2.303 RT log K
The larger the decrease in ∆G,

The larger
g the value of K,
The further the equilibrium lies in
favor of products
G o  O , K 1
G o  O , K 1
G o  O , K 1
Systems tend to move towards their most stable state. G o  0
G o  H o  TS o
 H o  0,  S o  0 G o  0
p : G o  0
at low temp
 H o  0,  S o  0
at high temp : G o  0
at low temp : G o  0
 H  0,  S  0
o o
at high temp : G o  0
 H o  0,  S o  0 G o  0
Usually, ∆H is more important than ∆S under ambient conditions.

G o  H o  TS o
Difference in energies between the bonds

H o
in the reactants and products
H   BDE (broken )   BDE ( formed )
S o Degree of disorder,
disorder translational
translational,
vibrational, rotational purpose
L
Largest
t iin magnitude!!
it d !!
Increase in the number of molecular

Increase in entropy
species from reactants to products
 H o  0,  S o  0
H   BDE (broken )   BDE ( formed )
G o  H o  TS o at low temp : G o  0

at high temp : G o  0
A + B C S o  0
G o  H o  TS o H o  0 (exothermi c reaction) : G o ???

H o  0 (endotherm ic reaction) : G o  0
 H o  0,  S o  0
H   BDE (broken )   BDE ( fformed )
G  H  TS
o o o at low temp : G o  0
at high temp : 
GGo  0
 H o  0,  S o  0
Intramolecular H
H-bond
bond vs Intermolecular H
H-bond
bond
 H o  0,  S o  0
G o  0
“How fast” the reactants are converted into the products?
G
 Go  0
2.2.1 Reaction Rate and free energy of activation
Transition State (activated complex)
Free energy of activation
G o  H o  TS o (for Energetics )

G  H ‡  T S ‡ (for Kinetics)
‡
Transition state is merely a highly unstable state that passes through in a

dynamic process, and not an intermediate!!
‡
‡
H E act (activatio n energy)
Energy necessary to effect the stretching or even breaking of bonds
k  Ae -E a /RT (Arrhenius Equation)

Ea
ln k  ln A 
RT
The value of Eact can be obtained graphically by plotting values of ln k
against 1/T.
‡
S
Related to randomness
Related to the A factor in the Arrhenius Equation
‡
‡
H E act (activatio n energy)
Ea Ea
k  A exp( ) ln(k )    ln( A)
RT RT
1. Obtain k vs T
 Plot ln(k) vs 1/T
 slope = - Ea/R
2. Obtain two k’s at two different temperature:
Ea  1 1 
ln(k1 / k2 )     
R  T1 T2 
‡
S
Related to the A factor
X-intercept lnA
2.2.2 Kinetics and the rate-limiting step
d [ A] d [C ]
Rate     k [ A] m [ B ] n
dt dt
Keep in mind,
The stiochiometry is no guide to the rate law.
The rate order (m and n) must be determined by experiments.
B ][OH  ]
R t  k [CH 3 Br
Rate
Rate  k [CH 3COCH 3 ][OH  ]

1. Thiss reaction
eact o is
s not
ot o
one-step
e step process.
p ocess
2. Bromine is not involved in the rate-limiting step.
3. Overall reaction must involve at least two steps.
ate  k [C
Rate CH 3COC OH  ]
COCH 3 ][O
‡ ‡
G1  G2
1. First step: RDS

1
2. Bromine: not involved in the
first step.
Experimentally determined rate equation

1. Give information about species in RDS
2. Give no information about the structure of TS
3 Give no direct information about the intermediate in the Non
3. Non-RDS
RDS steps
How we get information about the structure of TS?

 Use the relevant intermediates as model compounds for TS
Hammond’s Postulate
The effect of a catalyst:
y increase the rat of a reaction
Make available an alternative path of less

energetic demand through the formation of a
new, and more stable intermediate
2.2.3 Kinetic versus thermodynamic control
Kinetic control: Thermodynamic control:
The proportion of the product The proportion of the product mixture
mixture is determined by their is determined by their relative
relative rate of formation thermodynamic stabilities
2.2.3 Kinetic versus thermodynamic control
Kinetic control:
the proportion of the product mixture is determined by their relative rate
of formation
y
Thermodynamic control:
the proportion of the product mixture is determined by their relative
thermodynamic stabilities
Thermodynamic control Kinetic control
More examples
Diels-Alder Reaction: endo-exo selectivity
2.3 Investigation of Reaction Mechanisms
2.3.1 The Nature of products
The most fundamental information about a reaction!!
Initially proposed structure
Expected 1H NMR spectrum: 30 aromatic Hs

Actual 1H NMR spectrum: 25 aromatic Hs + four dienic Hs + one aliphatic H
2.3.1 The Nature of products
When more than one product is formed, it is an advantage to know the
structure
t t off products
d t and
d their
th i ratio.
ti
SNAr?? Rule out SNAr

2.3.2 Kinetic data
The largest body of information about reaction pathways comes from
ki ti studies.
kinetic t di
However, the interpretation of kinetic data is not always as simple!!
Rate  k [ R  Hal ]
Can we conclude that water does not participate in the RDS?
Rate  k [ R  Hal ][ H 2 O ]
Can we conclude that water does participate in the RDS now?
Actual mechanism for hydrolysis might change depending to the

reaction media (solvent).
2.3.3 The use of isotope
Primary kinetic isotope effect:
Tell whether the chemical bond concerned is broken in the RDS.
RDS
C H bond cleavage is involved in the RDS?

C-H
kH
 6 .7
kD
In the RDS, the C-H bond

C-D bond is stronger than C-H bond cleavage occurs.
Tell whether the chemical bond concerned is broken in the RDS.
RDS
kH
1
kD
The C-H bond breaking g is

not involved in the RDS.
kH
 27 Strong evidence that C-H bond
is being broken in the RDS!!!
kD
Can we apply primary KIE to other atoms than hydrogen?
k 12 C
 1.09
k 14 C
k 35 Cl
 1.0076
k 37 Cl
Since the relative mass difference is smaller,

their maximum values is accordingly smaller!!
kH
 27 Strong evidence that C-H bond
is being broken in the RDS!!!
kD
More examples
kH
 4 .0
kD
CH3 H3C
kH
H3C Br + H2O CH2  1 .0
CH3 H3C kD
Isotope Labeling Experiments
Hydrolysis of ester
How to discriminate the reaction pathway between them?

Isotope Labeling Experiments Where this hydrogen
y g is from?
Cannizzaro reaction
Elucidation of biosynthetic pathways: use 14C isotope
1) 14CH3CO2H O OH 1) 8 14C atoms
O O
2) CH314CO2H 2) 9 14C atoms
O OMe
sterigmatocystin
Major challenges in isotope experiments

1. Incorporation of isotopes at the specific position
2. Find where the label is located in the products
NMR technique could tell where the labels are unequivocally!!
2.3.4 The Study of intermediates
1. Isolation of intermediates
Hofmann reaction
Can be isolated
1. Need to show that the isolated intermediate can be converted into

the p
product under normal reaction conditions.
2. Need to establish that the isolated intermediate is on the direct
pathway, and not merely in equilibrium with the true intermediate.
2. Spectroscopic detection of intermediates
Detected in IR
3. Trapping:
Converting the labile intermediate from the reaction pathway into the
stable species
Carbene Intermediate
B
Benzyne IIntermediate
t di t
2.3.5 Stereochemical criteria
Cannot be direct, one-step addition of bromine to the double bond!!

2.3.5 Stereochemical criteria
“Lasso Chemitry”
Groups are eliminated most readily when closest together.
together

Chapter 2 Energetics, Kinetics, and The Investigation of Mechanism

Uploaded by

Copyright:

Available Formats

Chapter 2 Energetics, Kinetics, and The Investigation of Mechanism

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Chapter 2 Energetics, Kinetics, and The Investigation of Mechanism

Uploaded by

Copyright:

Available Formats

2.

Energetics, kinetics, and investigation of mechanism

2.1 Energetics of Reaction

2 3 Investigation of Reaction Mechanisms

The larger the decrease in ∆G,

Usually, ∆H is more important than ∆S under ambient conditions.

Difference in energies between the bonds

Increase in the number of molecular

G o  H o  TS o at low temp : G o  0

G o  H o  TS o H o  0 (exothermi c reaction) : G o ???

Transition State (activated complex)

Free energy of activation

G o  H o  TS o (for Energetics )

Transition state is merely a highly unstable state that passes through in a

k  Ae -E a /RT (Arrhenius Equation)

2. Obtain two k’s at two different temperature:

Rate  k [CH 3COCH 3 ][OH  ]

1. First step: RDS

Experimentally determined rate equation

How we get information about the structure of TS?

Make available an alternative path of less

Thermodynamic control Kinetic control

Initially proposed structure

Expected 1H NMR spectrum: 30 aromatic Hs

SNAr?? Rule out SNAr

Can we conclude that water does participate in the RDS now?

Actual mechanism for hydrolysis might change depending to the

C H bond cleavage is involved in the RDS?

In the RDS, the C-H bond

The C-H bond breaking g is

Since the relative mass difference is smaller,

How to discriminate the reaction pathway between them?

1) 14CH3CO2H O OH 1) 8 14C atoms

Major challenges in isotope experiments

1. Need to show that the isolated intermediate can be converted into

Cannot be direct, one-step addition of bromine to the double bond!!

You might also like