Kinetic Analysis of

Spectroscopic Data
Koushik Ponnuru
April 16 2015

Research Plan

Outline
Comparison of classical Kinetic methodology vs.
kinetic analysis of in-situ Spectroscopic data
Driving Force Analysis - Different Excess Protocol
Process Robustness Analysis - Same Excess Potocol

Spectroscopic data

Concentrati
on

Changes in absorption
correlated to the
concentration of the
species

ReactIR 45M fitted with a dicomp

ATR probe

time

J. Am. Chem. Soc. 2012, 134, 46

Reaction progress Kinetic Analysis

Typical trace of reactant
consumption over time:
One initial rate
point per
experimental run

RPKA teaches us how to

extract information from here
Extract Kinetic Information
Concentration Dependence
Catalyst Stability Analysis

Classical Methodology measures a

small change in concentration at
the beginning of the reaction over a
short period of time

Classical Kinetic methodology :

Drawbacks
Diels Alder
Reaction

Drawbacks
Large number of separate
experiments required
Concentrations are
distorted from
synthetically relevant
conditions

Elementary Reactions : Different

Excess
Diels Alder
Reaction

Difference between
concentrations
Excess [e] = [2]0 [1]0 = [2]
[1]
[2] = [1]+ [e]

[e] has units of concentration

[e] does not change as the reaction
progresses

If we know the concentration

of one we know the
concentration of the other

Kinetic Analysis of Elementary

reactions
Exp. A
Exp. B

[1]0

[2]0

0.2M
0.2M

0.6 M
0.4M

[e] = [2]0 [1]0 =

[2] [1]
0.4 M
0.2M

JACS, 2007,129,15100.

We See curvature because

both [1] and [2] are changing
over the course of the
reaction

Kinetic Analysis of Elementary

reactions
Rearranged rate
Rate equation
equation

Rate Law for Catalytic Cycle

JACS, 2007,129,15100.

St
ea
ra dy
te st
la a t
w e

w
a

er m
r
w
o
Po f

Approxima
tes
This form

Rate Law for Catalytic Cycle

Plot the normalized form of

the power law rate equation
for two different excess
experiments

When Y is chosen correctly,

we obtain straight lines
When X is chosen correctly,
the two curves overlay

Amino acid catalyzed aldol

condensation

1.5M
0.75
M

Same Excess Protocol Explained

The working system after 50
turnovers

The fresh system at the same

concentration

If the catalyst is robust the rates should be identical at this

Same Excess Protocol Design

Conditions
Same Excess I @ 25%

conversion
Same Excess II @ 0%
conversion

If the simple catalytic cycle

truly describes the process,
then at a given set of
concentrations, the fresh and
the working systems should

Proline Catalysed Aldol reaction : Role of water

[e] = 0 M

Red Data :
0.5M
Blue Data:
1.0M

0.5M
1.0M

Second
Experiment starts

No overlay : process is not

robust

overlay : process is robust

Role of water in the catalytic cycle

JACS, 2007,129,15100.

True mechanistic dependence of rate

on H20
Rate = Kobs
[H20]0.7
Under the conditions where
the catalyst concentration is
stable within the cycle
addition of water suppresses
the rate within the cycle

Role of water in the catalytic cycle

Water suppresses the side

reaction that consumes the
reactant E and removes the
catalyst from the cycle
Therefore addition of water
increases the yield
Water suppresses the rate of
main catalytic cycle
Water decreases the rate

Safety moment
DMSO
Slightly hazardous in case of inhalation, ingestion, and skin contact
Flammable in presence of open flames and sparks

2-Chlorobenzaldehyde
Very very hazardous in case of skin contact, eye contact, ingestion, and inhalation
Combustible liquid with a flash point between 37.8C (100F) and 93.3C (200F)

Acetone
Flammable liquid flash point below 100 F
Produce CO upon combustion
Hazardous in case of skin contact (irritant), of eye contact (irritant), of ingestion,
of inhalation. Slightly hazardous in case of skin contact (permeator)

Summary
Same Excess protocol
Catalyst Stability / process robustness
Comparison between on cycle vs. off cycle
processes
Different Excess Protocol
Reaction orders in substrate concentrations
Rate constants
Provide full kinetic analysis from a minimum
number of experiments

THANKS FOR YOUR

ATTENTION