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Synthesis of Benzilic Acid
Objectives
 To synthesize Benzilic acid using a solvent free Green Chemistry procedure
K. Tanaka and F. Toda, Chem. Rev., 2000, 100, 1045.
 To investigate a carbon skeleton rearrangement reaction.
 To assess the purity of the product by determining its melting point.
 To determine the molar mass of the product via titration with standardized NaOH.
In the Lab
 Students work in pairs
After Lab
 Complete the Chem21 assignment
Waste
 Place the fluted filter paper in regular trash.
 Place the aqueous filtrate down the sink with plenty of water.
 Place the first three titration solutions (KHP titrations) down the sink with plenty of
water.
 Place the last three titration solutions (Benzilic acid) in the waste container labeled
Lab 17 - Aqueous Ethanol Waste located in the Instructor’s hood.
Safety
 Students must wear goggles for this experiment.
Mechanism
Benzilic acid, although posing no threat itself, is a precursor and degradation product of a
chemical warfare agent called “BZ”.
BZ’s IUPAC name is -hydroxy-phenylbenzeneacetic acid-1-azabicyclo[2.2.2]oct-3-yl ester (see structure below).
OH
O
This compound is a psychogenic agent that incapacitates
C C
its victim. Approximately 30 minutes after exposure,
disorientation and visual and auditory hallucinations
O
N
begin to appear. After four hours and lasting four days,
symptoms can include distended pupils, dry mouth, and
increased body temperature. Most of these symptoms are
the result of BZ’s action on the central and peripheral nervous system via its binding to
muscarinic acetylcholine receptors. Production of BZ began in the United States in 1962 at
Pine Bluff Arsenal in Arkansas. It was later weaponized in bomblets with a pyrotechnic
mixture which, when ignited, produced a solid aerosol of the high-melting BZ. Between
1988 and 1990, the BZ munitions were destroyed and no BZ munitions remain in the US
stockpile.
The evidence proving that this nerve agent was used in warfare rests upon the detection of
benzilic acid (the compound we will make in this lab) in soil and water samples. This can be
accomplished using various instruments/techniques such as GC (gas chromatography), MS
(mass spectrometry), NMR (nuclear magnetic resonance spectroscopy) and LC (liquid
chromatography). To date, only one allegation of its use has surfaced – this from Bosnian
refugees. However, no soil or water samples were available to substantiate their allegations.
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17
• Benzilic acid
Today’s lab uses a “green chemistry” approach that uses fewer, and less expensive reagents
and solvents. Most other procedures use 95% Ethanol as the solvent and its removal requires
time and energy. In addition, these procedures use the more expensive KOH as the base.
Finally, these procedures use decolorizing carbon and celite in their purification schemes.
The “green” procedure, devised by K. Tanaka and F. Toda, uses only solid NaOH, water and
conc HCl to accomplish the same reaction in a shorter amount of time with similar yields.
Table of Physical Constants
n 20
Molecular Melting Boiling
Density D
Weight
Point Point
Chemical Name
Chemical
Formula
Benzil
C6H5COCOC6H5
210.23
Conc Hydrochloric
Acid
HCl
36.46
Benzilic Acid
(C6H5)2C(OH)CO
OH
228.25
Table 1
94-95
1.23
1.200
150-153
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• Benzilic acid
13. Collect the crystals via vacuum
filtration and wash twice with 50 mL ice
cold water.
14. Spread the crystals out on a labeled,
weighed watch glass and place
them in the drying oven for 30
minutes.
15. Weigh the product, record
~½ inch
the mass of the Benzilic Acid
of water
[Data Sheet].
16. Determine the melting
point [Data Sheet] of the
crystals and calculate the
percent yield [Online Report
Sheet].
Day 1 – Making Benzilic acid
1. Pack a melting point tube with the
benzil from Lab 16. Leave 0.5 grams of
the benzil in the labeled vial.
2. Place the rest of the
benzil in a mortar.
3. Wear Gloves!! Add
an equivalent mass of
NaOH to the mortar.
4. Place the mortar on
the counter top and use the
pestle to crush the NaOH
pellets. Once they are
crushed, grind the two
solids to make an easy
flowing powder (~ 2
minutes).
5. Transfer the powder to a 250 mL
Erlenmeyer flask and place the flask in a
600 mL beaker that contains ½ inch of
distilled water.
6. Heat the flask at 100°C for 20 minutes.
7. At the end of 20 minutes, place the
flask on the counter top and add to it 15
mL of the boiling water from the 600 mL
beaker.
8. Swirl to dissolve the solid. Filter the
solution through a fluted filter paper and
rinse the flask / filter paper with an
additional 5 mL of hot distilled water.
9. Cool the solution in an ice / water bath
for 10 minutes.
10. Add conc HCl, with stirring / swirling,
until there is obvious crystal formation.
11. Check the pH with pH paper. If the
pH is greater than 2, add conc HCl until
the pH is 2 or less.
12. Cool the solution in ice for 5 minutes.
Standardizing
the
NaOH
solution
17. Obtain ~200 mL of a sodium
hydroxide solution that is ~ 0.05 M in a
clean beaker. Label the beaker – either
mark on the beaker or write NaOH on a
piece of paper and set the beaker on top of
the paper.
18. Obtain a clean buret and buret clamp.
Make sure the stopcock on the buret is
closed.
19. Add ~ 5 mL of the NaOH solution
(from Step 17) to the buret (rotate the
buret to wash down the sides with this
NaOH solution) and empty it into a beaker
designated for waste.
20. Repeat Step 19.
21. Fill the buret to the top with the NaOH
solution. Place the beaker containing the
waste NaOH under the stopcock and fully
open the stopcock allowing ~1 mL of base
to exit. Repeat opening and closing the
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17
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stopcock until no more air bubbles exit
the tip of the buret.
22. Obtain three 200 (or
250
or
300)
ml
Erlenmeyer flasks. Tare
a weighing paper (make
sure the balance is not
fluctuating due to air
currents).
Using a
spatula, place 0.3 - 0.4 g
Potassium
hydrogen
phthalate (KHP) on the
weighing paper and close
the lid to the balance to
minimize air currents.
Record exactly the mass
of KHP [Data Sheet].
colorless solution to a persistent (for at
least 1 minute) light pink.
28. Record the final volume
of base used [Data Sheet].
Remove Air
Bubble In
Buret Tip.
29. Determine the Molarity
of the NaOH solution
[Online Report Sheet].
30. Repeat Steps 22 – 29 for
Flasks 2 & 3 – record the
data.
31. Determine the average
Molarity of the NaOH
solution from the 3 Trials
[Online Report Sheet].
Titrating Benzilic acid
23. Add the KHP, 100  5 ml of distilled
water, and three drops of the
phenolphthalein indicator to Flask 1.
32. Accurately weigh (to three significant
figures) approximately 0.2 g of Benzilic
acid (obtain this from your Instructor
while your Benzilic acid is drying in the
oven) using weighing paper [Data Sheet].
24. Place a stir bar in the flask and place
the flask on a stirring plate.
25. Adjust the buret so that it is directly
above the flask and the stirring plate.
33. Place the weighed Benzilic acid into
three different 125 (or 250)
mL Erlenmeyer flasks.
26. Record the volume of
NaOH in the buret [Data
Sheet] and begin to slowly
add the base to Flask 1.
27. As base drops onto the
acid solution, a pink color
appears
that
rapidly
disappears with stirring.
As time passes, the color
remains longer – you
should add the base
dropwise at this point.
Eventually, one drop of
base will change the
• Benzilic acid
Light pink
for 1 minute
34. Dissolve the acid in each
flask with 50 mL of 50%
aqueous
ethanol
(the
Benzilic acid does not need
to completely dissolve since
it will dissolve as it is
titrated).
35. Add 3 drops of a
phenolphthalein indicator.
36. Record the starting buret
volume [Data Sheet].
37. Titrate the Benzilic acid
solution to a light peach endpoint - the
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color change will be obvious, but not as
obvious as a colorless solution turning
pink. Make sure the peach color persists
for 1 minute to allow any undissolved acid
to dissolve.
17
• Benzilic acid
Lab Report
Once you have turned in your Instructor
Data Sheet, lab attendance will be entered
and you will have access to enter your lab
data online and begin the lab submission
process. Enter you lab data before exiting
the lab - enter your data accurately to
avoid penalty. The lab program will take
you in order to each calculation. Mouse
over the orange “TOL” link to see the
points and tolerances for each calculation.
38. Record the final buret volume [Data
Sheet].
39. Repeat Steps 36 – 38 for Flasks 2 &
3 – record the data.
40. Calculate the molar mass of benzilic
acid for each titration [Online Lab Sheet].
41. Determine the average molar mass of
Benzilic acid [Online Lab Sheet].
42. Turn in the Benzilic acid crystals in a
labeled vial with your lab data sheet.
Lab 17
Benzilic acid
Name:
Mass:
6
g
17
Synthesis of Benzilic Acid
Student Data Sheet
Mass of Benzil used
KHP
g
Mass (g)
Initial Volume
NaOH (mL)
Final Volume
NaOH (mL)
Mass (g)
Initial Volume
NaOH (mL)
Final Volume
NaOH (mL)
Titration 1
Titration 2
Titration 3
Benzilic Acid
Titration 4
Titration 5
Titration 6
Total mass of Benzilic Acid produced
g
ºC
Melting Point Range of Benzilic Acid

Name:
Partner:
Synthesis of Benzilic Acid
Instructor Data Sheet
Mass of Benzil used
KHP
g
Mass (g)
Initial Volume
NaOH (mL)
Final Volume
NaOH (mL)
Mass (g)
Initial Volume
NaOH (mL)
Final Volume
NaOH (mL)
Titration 1
Titration 2
Titration 3
Benzilic Acid
Titration 4
Titration 5
Titration 6
Total mass of Benzilic Acid produced
g
ºC
Melting Point Range of Benzilic Acid
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Post Lab Quiz (15pts)
At the beginning of the next lab period, you will have a quiz over the questions below. You
will be given the entire question and any structures on the in-class quiz. You may work
together prior to the in-class quiz to find the correct answers.
1 In this lab, a molecular rearrangement, specifically a 1,2-phenyl shift, occurs as shown in
the mechanism. While we have studied similar “shifts” last semester, the intermediate in
the reaction performed in this laboratory is different and the mechanism is different.
What are the names of the other two “shifts” and what intermediate is formed in these
reactions prior to the “shift”? Also, what is the “driving force” for these latter two
reactions (i.e. why does rearrangement even occur)?
2 In fact, this benzilic acid rearrangement is the oldest known molecular rearrangement;
discovered by Justus von Liebig in 1832. How might you synthesize benzilic acid
starting from benzene going through benzophenone and a cyanohydrin intermediate and
finally producing benzilic acid.
3 Assign oxidation numbers to the carbon atoms in Benzil and benzilic acid (see Lab 16
introduction for assigning oxidation numbers). According to your numbers, has an
oxidation or reduction (or neither) occurred?
O O
C C
OH-
OH
C C
O
H+
-
O
OH
C C
O
OH
4 Binding studies on stereoisomers of 3-quinuclidinyl esters (BZ being one such ester) have
shown that it is the (R)-stereoisomer that has the greatest affinity for the muscarinic
acetylcholine receptors. Using a dash or wedge (the structure will be provided on the
quiz), show the R stereoisomer of BZ.
5 BZ’s IUPAC name is α-hydroxy-α-phenylbenzeneacetic acid-1-azabicyclo[2.2.2]oct-3-yl
ester. To what atom(s) do(es) the term “aza” refer? To what does the [2.2.2] refer?
Explain fully (hint: look up “bicyclo" in the McMurray text book).
8
17
6 What aldehyde would you use to prepare the following compounds (these products are in
every way analogous to the benzaldehyde  benzoin  benzil  benzilic acid
reactions studied in Experiments 15 – 17).
OH
OH
a)
CH3O
C
O
b)
COOH
C COOH
O
OCH3
7 Give a mechanism for the following transformations (this mechanism is in every way
analogous to the benzil  benzilic acid mechanism seen in this very lab).
O
O
OH
COOH
1) HO2) H+
8 Alpha hydroxy acids (AHAs) have been marketed and used extensively in the past two
decades by older consumers. Use the Internet or resource book to determine why AHA
producers have enjoyed widespread financial success.
9 Another AHA that forms in milk as it sours and is produced in muscles and blood after
vigorous exercise is lactic acid, CH3CH(OH)COOH. The maximum number of
stereoisomers of a given substance is 2n where n is the # of stereogenic centers. What is
the maximum number of stereoisomers possible for lactic acid? Draw all stereoisomers
and label all stereogenic centers as “R” or “S”.
9