Sahaya Asirvatham

lAn element is identified by its symbol, mass number,

and atomic number.

lThe atomic number is the number of protons in the

nucleus while the mass number is the total number of

protons and neutrons in the nucleus.

lIsotopes are two atoms of the same element that have

the same number of protons but different numbers of

neutrons. Isotopes are specified by the mass number.

Why Kinetic Isotope effect???

Traditional kinetics studies do not provide

information as to what bonds are broken/formed

and changes in hybridization that occur during the

rate limiting step of a reaction.

Isotope effects can provide this information.

Substituting one iosotope for another at or near an

atom at which bonds are breaking or re-hybridizing

typically leads to a change in the rate of the

reaction.

Kinetic Isotope Effects

The kinetic isotope effect (KIE) is a

phenomenon associated with isotopically

substituted molecules exhibiting different

reaction rates.

Differences in the properties which arise from the

difference in mass are called as isotope effect.

Rates of reactions are measurable different for the

process in which E-H & E-D bonds are broken,

made or rearranged (E – another element).

The detection of this kinetic isotope effect help to

support a proposed reaction mechanism of many

chemical reactions.

The isotope effect is expressed as a ratio of rate

constants:

The rate constant for the reaction with the natural

abundance isotope over the rate constant for the

reaction with the altered isotope.

For H/D substitutions: kH/kD

The magnitude of the IE gives information about

reaction mechanism:

If kH/KD = 1, the bond where substitution has

occured is not changing during the chemical

reaction (RDS)

OR The IE is negligible to be measured

If kH/KD > 1, the IE is Normal IE

If kH/KD < 1, the IE is Inverse IE

Primary kinetic isotope effects

A Primary Kinetic Isotope effect may

be found when a bond to the

Isotopically labelled atom is being

formed or broken.

Origin of Primary Kinetic Isotope Effects

The origins of isotope effects is the difference in the

frequencies of various Vibrational modes of a

molecule, arising when one isotope is substituted for

another.

Different type of bond in a molecule have different

frequency.

Vibrational frequancy of a molecule is calculated by

using the formula:

Where Mr = Reduced mass

The VF is directly proportional to FORCE constant

‘k’ and inversely proportional to the mass of the

atom.

As deuterium is heavier than hydrogen the VF of

C-H bond will be more as compared to C-D bond.

Energy for bond breaking is directly proportional to

VF

Thus energy for C-H bond will be less as compared

to C-D bond.

Vibrational energy which is calculated at

ambient temperature for bond is called Zero

Point energy (ZPE)

Zero Point energy (ZPE) can be stated as,

Example

lDehydrohalogenation reaction

lWithout isotope:

lCH3-CH2-CH2-Br CH3-CH=CH2

lWithout isotope:

lCH3-CD2-CH2-Br CH3-CD=CH2

NaOC2H5

C2H5OH

NaOC2H5

C2H5OH

kH/kD= 6.7

Secondary Kinetic Isotope Effects

lWhen the IE is attributed to a REHYBRIDIZATION or when IE

arises from substitution remote/away from the bond

undergoinig reaction it is reffered to as Secondary IE.

lα or β secondary isotope effects: based on whether the

isotope is on a position α or β to the bond that is changing.

In Secondary IE we consider change in Hybridization of

Carbon atom.

As the hybridization state of carbon changes the VF of C-

H and C-D bond will change

When C-H bond involving an sp3 hybridized carbon is

changing to a bond involving an sp2 hybridized carbon

the vibrational modes changes.

C-H bond strengths decrease in the order sp > sp2 > sp3

Hybridization Changes

Consider the in-plane and out-of-plane bending motions for sp3 and sp2

hybridized carbons, along with the associated IR frequencies.

The in-plane and out-of-plane bends for an sp3 hybridized carbon are

degenerate.

However, the in-plane bend is a much stiffer motion for the sp2 hybridized

carbon than is the out-of-plane bend ---- because of Steric Hindrance

This large difference in force constant for the out-of-plane bend

of an sp3 hybrid vs sp2 hybrid leads to -----

Significant difference in ZPE differences between C-H and C-D

bonds in reactions that involve rehybridization between sp3 and

sp2.

Therefore, it is this bending mode that leads to a measurable

Secondary Isotope Effect.