Experiment: Kinetic vs.

Thermodynamic Control of Organic Reactions

Kinetic vs. Thermodynamic Control

During your study of reactions this year you have examined many mechanisms. You have used
these mechanisms to predict which one of two possible organic products would be formed
exclusively or as the major product. You have also used them to predict which product would
form faster. Usually, the product formed in greater quantity is also the product formed faster.
This is because, in the rate determining step, one of the two products is more stable than the
other. The transition state for this step resembles the products, so the more stable product has a
more stable transition state leading to it, which in turn lowers the energy of activation. The now
familiar set of potential energy curves below shows this clearly.

less stable TS with higher Ea

Potential
Energy less stable product
more stable product

Progress of Reaction

The more stable product is called the thermodynamically controlled product. The product
formed by way of the lower energy of activation pathway forms faster and is referred to as the
kinetically controlled product. In the case discussed above, the same case you have seen over
and over this year, the kinetically controlled product (the one formed faster) and the
thermodynamically controlled product (the more stable one) are the same. The more stable
product is formed faster.

But there are exceptions to this common scenario. One of them is the formation of 1, 2- and
1, 4-addition products from conjugated dienes. You have probably studied this reaction already,
and it would be a good idea to review it before doing this experiment. Another is the formation
of semicarbazones, reactions that you will be doing in this experiment. In these exceptions, the
product that forms faster (the kinetically controlled product) is the less stable product, while the
more stable product (the thermodynamically controlled product) has a higher energy of
activation leading to it and is formed more slowly. In the reactions to be studied in this
experiment, you will allow an aldehyde (2-furaldehyde) and a ketone (cyclohexanone) to react
with semicarbazide hydrochloride to form semicarbazone products called 2-furaldehyde
semicarbazone (FS) and cyclohexanone semicarbazone (CS) respectively.

O O
H+
NNH C NH2 + H 2O
O + NH2NH C NH2
C
O O
H H

2-furaldehyde semicarbazide 2-furaldehyde semicarbazone

(F) (S) (FS)

O
O O H +
NNH C NH2
NH2NH C NH2
+ H2O

cyclohexanone semicarbazide cyclohexanone semicarbazone

C (S) (CS)

One of these reactions is kinetically controlled. The product of this reaction is the one that forms
faster. The other reaction is thermodynamically controlled. The product of this reaction is the
more stable product. For this pair of reactions, the thermodynamically controlled product is not
the same as the kinetically controlled product. One of the products, either FS or CS, will be the
kinetically controlled product. The other product will be the thermodynamically controlled
product. Let’s look at a generalized reaction in which A and B react with semicarbazide to form
S and BS.

A + S → AS

B + S → BS
Potential
Energy B+S

A+S
AS (kinetic control)
BS (thermodynamic control)

Progress of Reaction
As these curves are drawn, AS is the product of kinetic control. It has the lower energy of
activation for formation, but it is less stable. It forms faster. BS is the product of
thermodynamic control. It is the more stable product, but it is harder to form because the energy
of activation for its formation is higher.

At all temperatures, AS, the kinetically controlled product, forms faster. BS, the
thermodynamically controlled product, forms more slowly. However, a careful look at the AS
energy curve shows that the activation energy for the reverse reaction of AS forming A and S is
not much larger than the activation energy for the forward reaction, the formation of AS. At
many temperatures, the A, S, AS system is a very reversible reaction. On the other hand, looking
at the BS energy curve shows that the reverse reaction has a very high energy of activation, one
that markedly slows down the reverse reaction of BS to form B and S. Thus the BS, once it
forms, reverses itself very little. Any equilibrium between BS, B, and S lies far to the BS side.
In summary, at all temperatures, AS more easily reverses back to A and S than BS does. While
AS forms faster, it is less likely to “stay formed.” BS, on the other hand, forms more slowly but
is more likely to “stay formed.”

In this laboratory period, you will be doing several experiments. In parts 1 and 2, you will be
preparing the pure semicarbazones of cyclohexanone and 2-furaldehyde. In parts 3a, and b,
equimolar amounts of cyclohexanone and 2-furaldehyde will be “competing” with each other to
react with a limited amount of semicarbazide. In other words, there is not enough semicarbazide
to react with all of the cyclohexanone and 2-furaldehyde present. Which semicarbazone forms in
greater quantity at different temperatures will tell us which one is the kinetically controlled
product and which one is the thermodynamically controlled product. In 3a, the competitive
reaction occurs at 0oC. Here, both reactions will be slow, but the kinetically controlled product
will form faster and stay formed more, because the low temperature will slow down the reverse
reaction. Because of the low temperature, the higher activation energy needed to form the
thermodynamically controlled product will greatly reduce the formation of this product.

The competitive reaction in part 3b occurs at a temperature between 80-85oC. Here, the
temperature is high enough to form the thermodynamically controlled product while both the
forward and reverse reactions of the kinetically controlled product occur faster too.

Part 4 consists of two parts. In 4a, cyclohexanone semicarbazone is mixed with 2-furaldehyde
and the mixture is allowed to sit together at 80-85oC for a few minutes. If cyclohexanone
semicarbazone is the kinetically controlled product, you would expect it to reverse itself, forming
cyclohexanone and free semicarbazide. The free semicarbazone could then react with 2-
furaldehyde to form the less reversible thermodynamically controlled product, 2-furaldehyde
semicarbazone. On the other hand, if cyclohexanone semicarbazone is the thermodynamically
controlled product, you would expect it not to reverse itself, forming no semicarbazide to react
with the 2-furaldehyde. You would be left with the unreacted cyclohexanone semicarbazone.
From the melting point of the product of part 4a, you will be able to determine whether
cyclohexanone semicarbazone is the kinetically or thermodynamically controlled product.
Similarly, by repeating this procedure in part 4b with 2-furaldehyde semicarbazone and
cyclohexanone, you will get supporting evidence for your conclusions. From parts 3a, b, and c
alone, you should be able to determine which semicarbazone is kinetically controlled and which
one is thermodynamically controlled. Similarly, your results from 4a and b alone should confirm
your conclusions from part 3. Together, your results from parts 3 and 4 should enable you to
conclude with confidence which semicarbazone is kinetically controlled and which is
thermodynamically controlled.

Melting Points of Mixtures

In all parts of 3 and 4, you will determine the composition of the products obtained from the
melting points of the product mixtures, so you will need to know something about how mixtures
behave when they melt.

Theoretically, a pure substance melts at a constant temperature. The melting point of pure
cyclohexanone semicarbazone is 166oC. This means that if heat is applied to a pure sample, it
will begin melting at 166ºC and the temperature will remain at 166ºC until the last bit of solid
has been melted. For pure 2-furaldehyde semicarbazone, which has a melting point of 202oC,
the same is true. [Note: In practice, when taking a melting point of a pure substance, the
melting point technique we use makes it nearly impossible for the start and finish of the melting
process to be at the same temperature. If the sample is heated slowly at the melting point,
approximately 2ºC or less per minute, then the melting point range of the pure sample will be
1ºC or less. This 1ºC melting point range is indicative of a pure substance.]

However, when solid X is contaminated with an impurity that is soluble in molten X, the melting
point of the impure sample is lowered and the melting point range, the range of temperatures
between the appearance of the first drop of liquid and the disappearance of the last bit of solid, is
broadened. For example, when a sample of pure 2-furaldehyde semicarbazone is contaminated
with a little bit of cyclohexanone semicarbazone, the melting point will drop below 202ºC and
the melting point range will broaden. Depending on the amount of contaminant present, the
melting point range might be 192-196ºC. Similarly, when a sample of cyclohexanone
semicarbazone is contaminated with some 2-furaldehyde semicarbazone, the melting point will
drop below 166ºC, even though the “contaminant” is the higher melting2-furaldehyde
semicarbazone. Thus, a sample of cyclohexanone semicarbazone (166ºC) with a small amount
of 2-furaldehyde semicarbazone (202ºC) may have a melting point range of 157-163ºC. The
more impurity that is present, the more the melting point is lowered and the broader the melting
point range becomes.

For mixtures containing two components, melting point diagrams like the one shown below can
be drawn. Consider two compounds, X (mp 125ºC) and Y (mp 175ºC). If a series of mixtures of
X and Y of known composition are made, and the melting points of the mixtures are determined,
a plot of melting temperature vs. composition might look like this.
 175ºC
Melting point of Y

125ºC
Melting point of X

Temperature

Eutectic Point

100% X Percentage of X (by mass) 0% X

(0% Y) (100% Y)

As you can see from this melting point diagram, as more and more Y is added to X and the
percentage of X decreases, the melting point of the mixture decreases. Similarly, as more and
more X is added to Y, and the percentage of Y decreases, the melting point of the mixture
decreases. The point where the two melting point lines meet is called the eutectic point.
(Eutectic means “easy melting” in Greek). The mixture of X and Y that has the composition
shown at this point is called a eutectic mixture. The eutectic mixture has the lowest melting
point that a mixture of two substances, in this case X and Y, can have. Unlike all other mixtures
of X and Y, the eutectic mixture has a constant melting point, much like that of a pure substance.
It begins and finishes melting at the same temperature.

In your pre-lab assignment, you will be making a melting point diagram like this from
experimental melting point–percentage composition data for 2-furaldehyde semicarbazone and
cyclohexanone semicarbazone. From this diagram and your own experimental data you will
determine the composition of the mixtures you obtain from parts 3 and 4. It is important to note
something here. On the diagram above, between the melting point of the eutectic mixture and
125ºC, each temperature corresponds to two different compositions of an X-Y mixture. You will
have to take this into account when determining the compositions of your semicarbazone
mixtures from parts 3 and 4 of the experiment. In some cases, it will not be possible to do more
than narrow down to two possibilities the composition based on the melting point of your sample
and the melting point diagram you will generate in the pre-lab work.
 Pre-lab Preparation

1. Read thoroughly the theory section of this experiment and the section in your lecture
textbook dealing with kinetic and thermodynamic control.

2. Carefully go over the procedure for this experiment, especially parts 3 and 4, to be sure
that you understand the purpose of each procedural step. Since you will be working
with a partner for this experiment, determine before you come to lab, which parts of the
experiment each of you will do. A logical breakdown of responsibilities would be for
one of you to do part 1 and either part 3 or 4 with the other of you doing the remaining
parts.

3. Answer the following questions about the AS and BS reactions discussed in the
background portion of this experiment.

a. When a competitive reaction occurs between A and B and a limited amount

of S, which product, AS or BS, would you expect to form in largest yield at
0ºC? Briefly explain.

b. Which product would you expect to form in largest yield at high

temperatures? Briefly explain.

c. If BS and A were mixed together with the appropriate solvents used

throughout the experiment and heated to the same high temperature as in “b”
above, what would you expect to happen? Briefly explain.

4. Using the following melting point-percentage composition data, draw a melting point
diagram like the one drawn for X and Y in the background section of this experiment.
Use the average melting point data for your graph, not the melting point range. Graph to
show the best fit line. Do not just “connect the dots”. To draw the best fit lines, do not
attempt to begin and end at data points. Instead, draw a line interpolating between all
points. To get a good graph, the lowest temperature on your y-axis should be 100ºC and
the graph should be sufficiently large to allow you to use it to answer post-lab questions.

% by mass of CS Melting point range (ºC) Average melting point (ºC)

100 165.2 - 166.8 166.0
90 144.9 - 160.0 152.5
80 140.0 - 144.0 142.0
70 143.7 - 148.4 146.1
50 143.0 -160.0 151.0
20 171.0 - 180.0 175.5
0 201.6 - 202.4 202.0
 Experimental Procedure

! Safety Considerations

! Semicarbazide hydrochloride is carcinogenic. Use gloves when working with this compound.
If you get any on your skin, wash it thoroughly with soap and hot water.

1. Preparing Cyclohexanone Semicarbazone

In a 50-mL Erlenmeyer flask, dissolve 1.0 g of semicarbazide hydrochloride and 2.0 g of

dibasic potassium phosphate (K2HPO4) in 25 mL of water. Using a 10-mL graduated
cylinder, measure out 1.0 mL of cyclohexanone and pour it into a test tube containing
5 mL of 95% ethanol. Pour this ethanol solution into the solution containing the
semicarbazide and swirl the mixture thoroughly to mix the reactants. Let the mixture sit
for 5-10 minutes to allow crystals of cyclohexanone semicarbazone to form.

Note: The reactions of aldehydes and ketones with semicarbazide hydrochloride

require that the pH of the solution be acidic but not too much so. The function of the
dibasic potassium phosphate is to assure the optimum pH for the reaction.

Note: Throughout this experiment, you will be allowing solutions to sit, waiting for
crystals of the semicarbazones to form. Sometimes these crystals form readily, and
sometimes they do not. Crystallization is a tricky thing in organic lab. When crystals are
slow in forming, cooling in an ice bath can help. So can scratching the sides of the
container with a glass stirring rod. The scratch mark made by the stirring rod can provide
a spot just right for molecules to collect and start developing a crystal. Once crystals start
to form, other crystals will form more rapidly.

Filter the crystals with suction using a Hirsch funnel. (A Hirsch funnel is a small, conical
funnel designed for suction filtration. It works exactly like a Buchner funnel except it is
used for filtering small amounts of solid. Use small pieces of filter paper that just cover
the holes at the base of the funnel.) Wash the crystals with 2-3 mL of cold water.
Remove the crystals, place them between two pieces of filter paper folded on the sides to
keep the crystals from falling out, and label them. Note the color of the crystals.

Set this solid aside for use in part 4.

The melting point of pure cyclohexanone semicarbazone is 166oC.

2. Preparing 2-Furaldehyde Semicarbazone

Repeat exactly the procedure for the preparation of cyclohexanone semicarbazone, using
0.8 mL of 2-furaldehyde instead of 1.0 mL of cyclohexanone. The melting point of 2-
furaldehyde semicarbazone is 202oC.

3. Competitive Reactions of Cyclohexanone and 2-Furaldehyde with Semicarbazide

Prepare the following solutions in appropriately sized Erlenmeyer flasks and stopper
them.

Solution S (semicarbazide solution)

Dissolve 2.0 g of semicarbazide hydrochloride and 4.0 g of dibasic potassium phosphate

in 50 mL of water.

Solution FC (furaldehyde and cyclohexanone mixture)

Dissolve 2.0 mL of cyclohexanone and 1.6 mL of 2-furaldehyde in 10 mL of 95%

ethanol.

a. In separate Erlenmeyer flasks, cool 5 mL of solution FC and 25 mL of solution S

in an ice-water bath at 0-2oC. Then add the cold solution FC to the cold solution
S, swirling well to mix the reactants. Crystals should form quickly. Keep the
reaction mixture at 0-2oC for 3-5 minutes after the crystals have formed. Vacuum
filter the crystals and wash them with 2-3 mL of cold water. Allow the crystals to
dry for at least 24 hours before taking their melting point.

b. In separate Erlenmeyer flasks, warm 5 mL of solution FC and 25 mL of solution S

in an 80-85oC water bath. After 5 minutes of warming, add the warm FC solution
to the warm solution of S and swirl well to insure thorough mixing of the
reactants. Heat the mixture in the hot-water bath for 15 minutes, cool it to room
temperature and then in an ice-water bath until crystals are formed. Scratch the
sides of the flask with a glass stirring rod if necessary to induce crystallization.
Vacuum filter the crystals, wash them with 2-3 mL of cold water, and let them dry
for at least 24 hours before taking their melting point.

Note: Students sometimes are confused in this experiment when they cool the
reaction mixture that has been heated at 85ºC for 15 minutes. They sometimes
think that cooling the reaction in ice water that they are changing the nature of the
products that were formed at 85ºC. The composition of the products will not
change upon cooling. The cooling is just to speed up the formation of crystals.
4. Testing for Reversibility: reacting semicarbazones with cyclohexanone and furaldehyde

a. Cyclohexanone Semicarbazone with 2-Furaldehyde

In a 25-mL Erlenmeyer flask, put 0.3 g of the cyclohexanone semicarbazone

prepared in part 1, 0.3 mL of 2-furaldehyde, 2 mL of 95% ethanol, and 10 mL of
water. Warm the mixture with swirling in an 80-85oC water bath until the solids
dissolve and then warm the mixture for 3 minutes more. Cool the mixture to
room temperature and then in an ice-water bath. Vacuum filter the crystals, wash
the crystals with 2-3 mL of cold water and allow them to dry for at least 24 hours
before taking their melting point.

b. 2-Furaldehyde Semicarbazone with Cyclohexanone

In a 25-mL Erlenmeyer flask, put 0.3 g of the 2-furaldehyde semicarbazone

prepared in part 2, 0.3 mL of cyclohexanone, 2 mL of 95% ethanol, and 10 mL of
water. Warm the mixture with swirling in an 80-85oC water bath until the solids
dissolve and then warm the mixture for 3 minutes more. Cool the mixture to
room temperature and then in an ice-water bath. Vacuum filter the crystals, wash
the crystals with 2-3 mL of cold water and allow them to dry for at least 24 hours
before taking their melting point.

5. Dispose of all filtrates, the liquids left over from crystal filtration, down the sink.
Leftover CF and S solutions will be disposed of in waste bottles in the hood

6. After 24 hours, take the melting points of all of your samples and record them in your
notebook. See Appendix 4 for details on how to correctly measure melting point. Your
instructor will show you how to crush your crystals, put them in a capillary tube and pack
the crystals in the tube. Your instructor will also talk to you about how to use the melting
point apparatuses in the lab and when to record the beginning and end of the melting
point range. To get an accurate and meaningful melting point range, the most important
thing is to heat slowly, at a rate of no more that 2ºC/minute. Heating any faster than that
near the melting point will cause your melting points to be too high and the ranges to be
too broad to be of value. When you have finished with your melting points, dispose of
the solid products in a waste jar in the hood.

 Post-Lab and Report Requirements

1. Write equations for the reactions of cyclohexanone and 2-furaldehyde with semicarbazide
in the presence of an HCl catalyst.

2. Give a theoretical discussion of the difference between a kinetically controlled product

and a thermodynamically controlled product. Be sure to explain how temperature affects
the product mixture in reactions such as the ones we studied in this experiment in which
 the kinetically controlled product and the thermodynamically controlled product are not
the same. Include a labeled energy diagram in your answer.

3. Give the experimental melting point ranges for each of the solids that you and your
partner made. For each of the sample mixtures of parts 3 and 4, average the beginning
and ending temperatures of the range and use this average temperature to determine the
approximate composition of the sample from the melting point diagram that you made for
your pre-lab assignment.

4. State which semicarbazone is the kinetically controlled product and which is the
thermodynamically controlled product.

a. Explain in detail how the results from the competitive reaction experiments in
experimental procedures 3a and b support this conclusion.

b. Explain in detail how the results from the experiments in experimental procedures 4a
and b support this conclusion