Linear Free Energy Relationships Lab
Part A: Synthesis of Standards
As a team, you need to reduce the following acetophenones:
 4-nitroacetophenone
 Acetophenone
 4-ethyl acetophenone
 4-methoxyacetophenone
 4-bromoacetophenone
Procedure: In a roundbottom flask with a magnetic stirbar, add 1 mmol of your acetophenone
derivative and dissolve it in 10 mL of ethanol. Add 1.5 equivalents of sodium borohydride (How many
mmols? Consider that there are 4 hydrides per borohydride) in three portions, slowly—don’t allow to
bubble over! Allow to stir for 10 minutes and then monitor reaction progress by TLC. Allow the reaction
to go until all starting material is consumed. Quench the reaction with 10 mL of 10% aqueous HCl, and
allow to stir for 5 minutes or until no gas is evolved. Extract the crude reaction with chloroform (3 x 10
mL), combine the organic layers and dry over sodium sulfate. Decant the liquid into a roundbottom
flask and remove the solvent under vacuum. Prepare a sample for proton NMR—Sarah will obtain the
data on a 400 MHz instrument.
Part B: Linear Free Energy Relationships
Pre-lab: Your team will need to choose which competitions to perform. Keep in mind that you should
not have a competition between two ketones of very different reactivities, but only between those of
relatively similar relativities. Which pairs should your class do? (HINT: Even though you eventually want
the relative rates for substituents compared to no substituent (acetophenone), not all of these
competitions are necessarily useful!)
Procedure: To a 50 mL roundbottomed flask with a stirbar, add a pair of acetophenone derivatives (1
mmol of each), followed by 20 mL of ethanol. Stir until dissolved. To this mixture, add sodium
borohydride (8 mg, 0.2 mmol) and stir for 15 minutes. [Hint: This is the most technically difficult part of
the lab. Work on being able to add 8 mg of a solid directly to a flask.] Quench the reaction with 20 mL
of 10% aqueous HCl. Extract the aqueous layer with chloroform (3 x 10 mL). Combine the organic
layers, dry over magnesium sulfate, filter, and evaporate the solvent. Obtain proton NMR data of the
crude mixture using CDCl3 as the solvent, with residual CHCl3 (7.26ppm) as an internal standard.
Part C: Data collection and analysis
You will collect proton NMR as the main data source in this lab. This is not trivial. You should be
prepared to spend some time obtaining good data. Be sure that you are consistent between your NMR
samples in terms of concentration, because NMR obtained at different concentrations can show
changes in chemical shift. Also, it is essential that the NMR run is well shimmed. In some cases, it is
difficult to separate the signals, and impossible if you observe line broadening. After obtaining data,
look it over carefully, and obtain a new NMR if yours is not readable.
Results and discussion:
LFER data: the following table should be used in data analysis:
Substitutent
Bromo
Ethyl
H
Methoxy
nitro
Sigma value
0.23
-0.15
What is this value?
-0.27
0.78
Some discussion questions to help guide you:
1.
2.
3.
4.
5.
Explain competition experiments, and how and why they were used to gather these data. How
were the pairings of acetophenone derivatives determined in order to get good data?
Explain how proton NMR was used to determine the product ratios of the reactions.
How were the NMR data used to determine relative rate data? Consider how you would use
tables/figures effectively.
Using Excel, draw a LFER diagram and determine the rho value for this reaction.
What is the significance of the rho value for this reaction? What does it tell you about the
mechanism of this reaction? Is the rho value in line with what you expected, based on your
understanding of the sodium borohydride reduction, or are these data unexpected?