Lalic, G.

Chem 530A

Chemistry 530A
Advanced Organic Chemistry
Lecture notes 10

Kinetics: A Practical Approach

Simple Kinetics Scenarios

Fitting Experimental Data

Using Kinetics to Determine the Mechanism

Dougherty, D. A., "Modern Physical Organic Chemistry", Chapter 7

p. 374-397.
Lalic G. Reaction Kinetics as a Tool in Studies Of Reaction Mechanism Chem 530A

Reaction Kinetics and Reaction Mechanism
The mechanism of the reaction tells us how the starting materials are
transformed into products. Ideally, we would like to know the energies of all the
SM, P, Intermediates, and all transition states (i.e. the full energy diagram).
Often we settle for less and we try to distinguish between several reasonable
general hypotheses.
The ultimate goal of kinetics experiments is to derive a rate law which gives
a quantitative relationship between the concentrations of the starting
materials and the rate of the reaction. That means that we know quite a bit
about the mechanism of the reaction.
We experimentaly observe the changes in concentrations of reactants,
intermediates, and/or products over time and try to fit the data to theoretical
rate laws that correspond to our mechanistic hypotheses. We also try to
determine kinetic order of reactants and the overall kinetic order of the reaction
which can be very helpful in discrediting wrong hypotheses.
Simple Kinetics Scenarios
-d[A]/dt = k[A][B] becomes d[P]/dt = -d[A]/dt = k1[B]
k1 = k[A]
Reaction becomes pseudo-first order. Behaves like it is 1st order, but it is not.
We use large excess of A relative to B, so [A] does not change during the
course of the reaction. This removes [A] for the overall order of the reaction.
As a reasult, we can isolate [B] and determine the order in B more easily.
Even when dealing with complicated reactions, we can isolate the influence
that the change in the concentration of one of the reagents has on the rate of
the reaction by making the starting concentration of all the other substrates
large relative to the substrate we are isolating, We usually need a 10 fold
excess of other substrates.
nA P
n-th order kinetics:
-d[A]/dt = k[A]n rate law
1/(n-1)(1/[A]n-1-1/[A]0n-1) = kt integrated rate law
Ideal picture looks like this (except for 0 order reactions):

relative concentration
First order kinetics: A P
d[P]/dt = -d[A]/dt = k[A] -d[A]/dt = k[A] rate law 1.0 [P] A+B P
ln[A] = ln[A]0 - kt integrated rate law
[A] = [A]0e-kt integrated rate law 0.5

Second order kinetics: 2A P

reaction is second order in A -d[A]/dt = k[A]2 rate law
1/[A] = kt + 1/[A]0 integrated rate law
A+B P
-d[A]/dt = k[A][B] rate law
[1/([B]0 - [A]0)]ln([A]0[B]/[B]0[A]) = kt integrated rate law
[B]0 = [A]0 goes to 1/[A] = kt + 1/[A]0
Pseudo-f irst order kinetics: A+B P the reaction flask).
0 [SM]
10xt1/2 t
0 t1/2 5xt1/2
Monitoring concentration changes over time:
Every kinetics experiment requires monitoring the change in the concentration
of the starting materials, products, and/or intermediates with time.
In Situ method: Concentration of relevant species is determined in situ,
usually by NMR (reaction performed in an NMR tube) or IR (IR probe inside

Sampling method: Taking samples from the reaction mixture at different time
What if, in a reaction of second order, [A] does not change during the points and determining concentrations of relevant species by an appropriate
course of the reaction? analytical technique (NMR, GC,HPLC, MS etc.).
Lalic G. Initial and "Total" Kinetics Experiments Chem 530A

Initial rate measurements "Total kinetics"

In the first 5 to 10% conversion, we can assume that the rate is constant We monitor the concentrations of relevant species throughout the course
because concentrations of reactants do not change significantly. As a result, of the rection. In pricinple, a single measurement does allow us to
we obtain a linear plot (relative concentration vs. time). The slope of this plot determine the overall order or the order in a reagent.
gives as the rate of the reaction.

relative concentration
1.0 [P]
relative concentration

0.1
-d[SM]/dt = d[P]/dt = rate
0.5
0.05 Slope = rate of the reaction

0 [SM]
0 t
0 t1/2 5xt1 10xt1/2
t
/2
A single measurement of initial rate does not allow us to determine the overall
kinetic order of the reaction or the kinetic order in any of the reagents.
If we repeat the experiment and systematically change [SM] under pseudo- To obtain information about the reaction's rate law, we fit the experimental
first order conditions we can obtaine the order in SM. data to the theoretical rate law in the integrated form. There are several
methods to fit the experimental data.
The shape gives us the order.
Flat line is 0, sloped line is a
first order first order, parabole is second
rate
order and so on. reaction rate integrated rate law
law
A P k[A] ln([A]/[A]0) = -kt
Notice that every data point is
a separate experiment in which 2A P k[A]2 1/[A] = kt + 1/[A]0
zero order we monitored change in [SM]
A+B P k[A][ [1/([B]0 - [A]0)]ln([A]0[B]/[B]0[A]) = kt
and/or [P] over time.
B] [B]0 = [A]0 goes to 1/[A] = kt + 1/[A]0
nA P k[A]n 1/(n-1)(1/[A]n-1-1/[A]0n-1) = kt
[A]0

Initial rate kinetics:

Direct fit:
Allows us to make certain simplifications because changes in
concentrations are small.
The experimental data are fitted directly to the integrated rate law in
Good for monitoring slow reactions. the form of [A] = f(t). Often, fit will be good for multiple rate laws and it
We assume that the first 5% of the reaction are representative of is hard to establish which one fits the best, but worth trying.
the whole reaction!
Lalic G. Mechanisms of Complex Organic Reactions Chem 530A

Consider the following transformation. What can we learn about the Kinetics
mechanism of this reaction from kinetics experiments?
Predictions
SN2 rate law rate = k1[RBr][CN]
Br + CN CN + Br
SN1 rate law rate = k2[R+][CN] [R+] hard to determine
Hypotheses:
steady state approximation (SSA)
SN2 k1 The net rate of the formation of I is assumed to be negligible.
Br + CN CN + Br
This approximation allows us to get a rate law independant of [R+]

k1 d[R+]/dt = 0 k1[RBr] = k2[R+][CN] + k-1[R+][Br]

SN1 CN
Br + Br CN + Br [R+] = k1[RBr]/(k2[CN] + k-1[Br])
k-1 k2
SN1 rate law rate = k2k1[RBr][CN]/(k2[CN] + k-1[Br])
Reaction diagrams of complex reactions SSA works often, because common intermediates are often unstable and an
appreciable concentration of intermediates rarely accumulated.
SN2 Single step. Elementary reaction.
If SSA is valid for a system then -d[SM]/dt = d[P]/dt.
TS
case 1:
E k2 > k-1 under normal reaction conditions [CN] ~ [Br] during
most of the reaction.

k2[CN] >> k-1[Br] rate = k1[RBr]

RBr
Intuitive picture: every time the cation is formed, it is trapped by CN,
RCN and it never has a chance to get back to bromide.
SN1 Two-step processes with two transition states. Assuming that we know This situation is discribed in the first reaction diagram. In this scenario, the
relative stabilities of all species involved, there are two scenarios: first step determines the rate of the overall reaction and we call this step
the rate determining step.
k2 > k-1 k-1 > k2 In general, the rate determining step is the step associated with the
E E highest energy transition state. Not the one with the highest activation
energy! This also means that this step is the first irreversible step.
However read the paper!!!!!!!

I I No k2, [CN]
or [Br] in
RBr RBr
the rate law
RCN Using kinetics experiments we cannot obtain information
RCN
about the parts of the reaction mechanism that take place after
the rate determining step.
Lalic G. Chem 530A
case 2: k2 ~ k-1 rate = k2k1[RBr][CN]/(k2[CN] + k-1[Br]) Initial rate
measurements
By changing the [CN]0 and [Br]0, we can change the rate law. At the high In the first 5 to 10% conversion, we can assume that the rate will be constant
enough [CN]0/[Br]0 ratio, the rate law will become k1[RBr]. because the concentrations of RBr and CN will not change significantly. At the
same time, [CN] is going to be much higher than [Br], and k2[CN] >> k-1[Br] is
likely to hold.
Rmax = k1[RBr] kmax = k1
saturated in CN Rinitial = k2k1[RBr][CN]/(k2[CN] + k-1[Br]) 0.1
R
-d[SM]/dt = d[P]/dt = rate
kinitial = k2k1[CN]/(k2[CN] + k-1[Br])
0.05 Slope = rate of the reaction
Rmax If [CN] and [Br] are constant, for
example, when [CN]0 and [Br]0 large:
kinitial = k1(1/(1+k-1[Br]/k2[CN]))
0
k-1[Br]/k2[CN] will always be positive so
t
kinitial < k1 0
[CN]0
Remember, a single measurement of initial rate does not allow us to determine
This is an example of saturation kinetics = reaching the [reactant] at the overall kinetic order of the reaction or the kinetic order in any of the reagents.
which rate becomes independant of the [ractant]. That usually means that we
changed the rate determining step. Then we vary [CN]0 while keeping [RBr]0 the same.
Does this mean that the reaction diagram changes as we change the
concentration of the reactants? NO! The diagram deals only with rate SN1 rate = k1[RBr]0 rate/[RBr]0 = k1 = kobs
constants and not with k2[CN] and k-1[Br]. In discussing the reaction kobs not a function of [CN]0
diagrams and rate determining steps, we assume that the concentrations of SN2 rate =k1[RBr]0[CN]0 rate/[RBr]0 = k1[CN]0 = kobs
species involved are similar. kobs is a function of [CN]0
case 3: What does the rate law simplify to if k-1[Br] >> k2[CN]?
kobs (1/s) SN2
Experiments
Slope is the order of
Several reasonable choices that would allow us to distinguish between
the reaction in CN.
SN1 and SN2.
Overall kinetic order of the reaction
SN1
Kinetic order in CN
Kinetic order in Br
[CN]0
The choice of our experiments depends on our intuition and practical
considirations. Order between zero and one would indicate the SN1 mechanism operating
under non-saturation conditions, or that both mechanisms are operational.
A reasonable start would be to use 1 equivalent of RBr and 1 equivalent of CN.
Lalic G. Competition Experiments Chem 530A

"Total kinetics" Could we use these reactions under these conditions to determine the relative
rates of reactions of these two nucleophiles with a carbocation?
We can do the experiment with [CN] ~ [RBr]. We can fit the data obtained
under these conditions using Van't Hoff's method and, with a little bit of The rate determining step obscures the kinetics of all subsequent steps.
luck, in a single experiment, we can obtain the overall order of the
reaction. If Van't Hoff's plot indicates that the reaction is first order, it is What if we did the same experiment but added both nucleophiles at the
likely SN1 in a saturation regime. If the plot indicates the second order, same time? (same conc. of nucleophiles simplifies the math, but it is not
than the reaction is likely SN2. Something in between would indicate that necessary)
we are in non-saturation regime or that both mechanism are operational.
SN1
If we want more inf ormation we can do the f ollowing: CN
CN
k 2CN
An experiment with high [CN] relative to [RBr] so that the reaction is pseudo- k1
first order. Besides, this maximizes the probability that the reaction operates in Br Br +
the saturation regime. k -1
N3
N3
k 2N3
By using Van't Hoff's method, we can obtain order in RBr from a single
measurement. By doing experiments with different [CN]0, we can obtain
kobs vs. [CN]0 plot that will give us order in CN. The observed ratio of the two products (product distribution) is a direct
SN1 rate = k 1[RBr]0 rate/[RBr]0 = k 1 = k obs reflection of k 2CN/k 2N3
k obs not a function of [CN]0
rate determining step
SN2 rate =k 1[RBr]0[CN]0 rate/[RBr]0 = k 1[CN]0 = k obs
k obs is a function of [CN]0 product determining step

Competition experiments
kobsCN
Br + CN CN + Br

kobsN3 RBr RN3

Br + N3 N3 + Br
RCN
If we did kinetics experiments with the same [RBr] in the saturation
regime with N3- and CN- as nucleophiles, would the rates differ? The rate of the reaction is determined by rates of all the steps prior to and
including the rate determining step, i.e., by all the steps that contribute to the
k1 Nu
SN1 rate law.
Br + Br Nu + Br
k -1 k2 The product distribution is determined by the relative rates of product
determining step(s).
-d[RBr]/dt = rate = k 2k 1[RBr][Nu]/(k 2[Nu] + k -1[Br])
Competition experiments allow us to gain insight into the product determining
k 2[Nu] >> k -1[Br] rate = k1[RBr] steps regardless of their position relative to the rate determining step.