Energetics, Kinetics and Investigation of

Reaction Mechanism

1
 Energetics of Reaction
 Deals with how far the reaction goes to the product

 System tend to move towards most stable state i.e., the more
stable the products compared with starting materials, the further
the equilibrium lies to the product.

 The larger the change in stability, the greater the conversion of

reactants to products 2
 The change in energy that occurs on going from reactants to
products is measured using heat of reaction, which is not
adequate measure of stability as there is no correlation between
∆H and equilibrium constant, K

 Exothermic reactions have only small equilibrium constants (little

conversion of starting materials to products), and some reactions
with larger equilibrium constants are endothermic.

 Hence some factors must be considered in measuring the relative

stability of chemical species in addition to enthalpy. This factor is
entropy: a measure of the degree of disorder of a system

 In seeking the most stable condition, system tends towards

minimum energy and maximum entropy which are provided by
the Gibb’s free energy given by
G = H-TS
3
 The free energy change during a reaction at a particular
temperature is given by ∆G = ∆H-T∆S

 The change in free energy at a standard state ∆Go in going from

the starting material to products is given as

-∆Go =2.303RTlogK, where K is equilibrium constant

 The larger the decrease (minus ∆Go ) in free energy on going from
starting material to products, the larger the K value, and the
further the equilibrium lies to products

4
Kinetics of Reaction
 The magnitude of ∆G tells us nothing about how fast the starting materials
are converted to products.

 For the oxidation of cellulose, ∆G o is negative and large in magnitude so the

equilibrium lies essentially to the products but the rate of conversion is very
slow

 The conversion of starting materials into products, despite large negative ∆G o ,

passes through a large barrier

5
Reaction rate and free energy of activation

 The least stable configuration through which the starting materials

pass during their conversion into products is called transition state
or activated complex. It is highly unstable and not a discrete
molecular species that can be detected and isolated.

 Consider the alkaline hydrolysis of bromomethane, where bond

formation and breaking occurs simultaneously

TS
 The reaction above is SN2
6
 The height of the barrier, , is called the free energy of activation for the reaction
(the higher it is the slower the reaction)

7
Kinetics and Rate limiting step

 Consider the reaction

Rate = k[CH3Br][OH-] where K is rate constant. The reaction is

second order overall and first order with respect to CH3Br and OH-

 The rate equation above tells us as bond formation and

breaking occurs at the slowest step, the step where rate is
measured.

8
 In the base catalyzed bromination of acetone

OH-
CH3COCH3 + Br2 CH3COCH2Br + HBr

Rate = K[CH3COCH3][OH-]

 In the rate equation bromine

doesn't appear but acetone and
hydroxyl do. Clearly bromine
must be involved at some stage in
the overall reaction as it is
incorporated in the product, but
it patently can not be involved in
the step whose rate we are
actually measuring. Such
reaction has to pass through an
intermediate. 9
 In the bromination of acetone, the steps involved are the rate
limiting removal of a proton by a base to form carbanion, which
then undergoes rapid, non-rate limiting attack by Br2 to yield
bromopropanone. The mechanism is depicted below

 The experimentally determined rate equation tells us

information about the species that are involved up to and
including the rate limiting step of the reaction.

10
 The effect of a catalyst is to increase the rate at which a
reaction will take place; this is done by making available an
alternative path of less energetic demand, often through the
formation of a new, and more stable intermediate.

 For instance the rate of hydration of olefins is slow but can be

speeded up by using acids as a catalyst.

11
Thermodynamic Versus Kinetic Control of Reactions

When a reaction produces more than one product, the

product that is formed most rapidly is called the kinetic
product, and the most stable product is called the
thermodynamic product.

Reactions that produce the kinetic product as the major

product are said to be kinetically controlled.

Reactions that produce the thermodynamic product as the

major product are said to be thermodynamically controlled.

12
Electrophilic addition to 1,3-butadiene is an example of a reaction in
which the kinetic product and the thermodynamic product are not the
same:

The1,2-addition product is the kinetic product, and the 1,4-addition

product is the thermodynamic product.

13
 Now we need to see why the 1,2-addition product is formed faster. In other

words, why is the transition state for formation of the 1,2-addition product
more stable than the transition state for formation of the 1,4-addition product?

14
Investigation of Reaction Mechanisms

1. Nature of products
 The most fundamental information about a reaction is provided by establishing the
structure of the products that are formed during its course, and relating this information
to the reactants.

 Information about the products of a reaction can be particularly informative when one
of them is unexpected.

 Compound 8 can not clearly be obtained by direct substitution which clearly shows as
both involve the same intermediate, called benzyne.

15
2. Kinetic data

 The largest body of information about reaction pathways come and still
come from kinetic studies. But the use of kinetic data to rationalize
mechanism is not as simple as expected

 If the hydrolysis of aqueous solution of the alkyl halide, RHal, is found

to follow the rate equation
Rate = K[RHal]
It is not necessarily safe to conclude that the rate limiting step does not
involve the participation of water, simply on the ground that the [H2O]
does not appear in the are equation; for if water is used as a solvent it will
be preset in large excess, and its concentration would remain virtually
unchanged.

 If you use formic acid as a solvent and water in small amount as a

potential nucleophile, the rate become

Rate = K[Rhal][H2O] 16
 3. The use of isotopes
 The vibrational frequencies of bonds and hence their bond dissociation
energies depend on their mass. Hence the greater the mass the stronger
the bond.

 A secondary kinetic isotope effect is observed when no bond to

the isotopically labeled atom in the reactant is broken or formed
17
 For instance, C-H bond breaks faster than C-D bond.

 It was found that the rate difference KH/KD is about 7 at 25oC.

Such difference is due to primary isotope effect

Thus in the oxidation

OH O

 It was found out the Ph2CHOH is oxidized 6.7 times faster than
Ph2CDOH; the reaction is said to be primary isotope effect and C-H
bond breaking occurs in the rate limiting step.

18
 On the other hand benzene and hexadeuterobenzene are found
to undergo nitration at essentially the same rate, and C-H bond
breaking, that must occur at some stage in the overall process,
thus cannot be involved in the rate limiting step.

19
 Isotopes can also be used to solve mechanistic problems that are
non-kinetic. Thus the aqueous hydrolysis of esters to yield and
acid and an alcohol could, in theory, proceed by cleavage at (a)
alkyl/oxygen fission, or (b) acyl/oxygen fission:

 If the reaction is carried out in water enriched in heavier oxygen

isotope 18O,
 will lead to an alcohol which is enriched with 18O and an acid
which is not, while
 will lead to an 18O enriched in acid indicating the hydrolysis under
these condition proceed via path way (b)
20
4. The study of intermediates

 Among the most concrete evidence obtainable about the reaction

mechanism is that provided by the actual isolation of one or more
of the intermediates from the reaction mixtures.
 Consider the Hofmann reaction by which amides are converted to
amines

 With care it is possible to isolate N-bromoamide, RCONHBr and

isocyanate, RNCO. The intermediates are different from side
products as they are converted to the desired products so fast.

21
 Consider the conversion of carbonyl compounds to oxime using
hydroxylamine. The formation of oxime can easily be deduced
from IR which tells us the disappearance of carbonyl and
appearance of an imine in the IT spectrum.

Oxime

 The presence of carbinolamine as an intermediate is a clear

evidence for the formation of the oxime

Carbinolamine

22
 Trapping intermediate
 If we suspect the involvement of a particular species as a labile
intermediate, it may be possible to confirm our suspicions by
introducing into the reaction mixture, a reactive species which
we should expect our postulated intermediate to react with
particularly readily.

 In the hydrolysis of trichlorometane with strong bases, the highly

electron deficient dichlorocarbene, was trapped by introducing
olefin into the reaction mixture, and then isolating the resultant
cyclopropane derivative

23
Exercises

25
1. Propose a rate law for each possible mechanism

2. Describe an experiment that could distinguish between the

two mechanism using KIE

26
2. When C-14 labeled chlorobenzene reacted with hot aqueous sodium
hydroxide, a 50:50 mixture of the C-14 labeled phenols shown below
were obtained. Propose an explanation for this finding and suggest a
reasonable mechanism for the reaction

Cl OH OH
14 14
1) hot aqueous NaOH 14
+
2) H3O

27
 3. When ketones are dissolved in H2O18 , the O18 is incorporated into
the carbonyl group. Draw reasonable mechanisms for this reaction
under acidic (H3O+/H2O), basic (–OH/H2O) and neutral conditions (H2O).

18
O H2O18 O
Me Me Me Me

28