Hiram College, Chem. 320: Spring 2010
Student Notes: Aldol-Dehydration Chemistry Using Unknown
Aldehydes and Ketones
nd
(ref: Modern Projects and Experiments in Organic Chemistry: Miniscale and Standard Taper Microscale, 2 edition, by Mohrig,
Hammond, Schatz, and Morrill, 2003, W.H. Freeman Company)
In this experiment you will:
Carry out an aldol condensation between an unknown aldehyde and an unknown ketone
Identify the aldehyde and ketone by MP
Analyze the NMR spectrum of the dehydration product of their aldol condensation
Prepare solid derivatives of the aldehyde and ketone and use their MP’s as additional data in
determining their identities
Techniques: suction filtration and melting points
Characterization: MP and 1H NMR,
Pre-Lab Assignments
Notebook
After table of reagents include: overall reactions for each part (draw the structures)
convert all amounts to moles
label the limiting reagent
calculate the theoretical yield
Questions (on a separate sheet of paper, turn in at the beginning of lab)
1. What are the structures of an “unknown” aldehyde and ketone that react with NaOH
in ethanol to form an aldol condensation product followed by its dehydration?
2. How can you use solid derivatives to confirm the structures of your “unknown”
aldehyde and ketone?
Waste Disposal: all filtrates-organic waste
1
Hiram College, Chem. 320: Spring 2010
Aldol Condensation-Dehydration Chemistry
The formation of carbon-carbon bonds is of fundamental importance in synthetic organic
chemistry, and the aldol condensation has a long and successful history as a method of carbon-carbon
bond formation. The base-promoted condensation of a molecule of benzaldehyde with a molecule of
acetophenone (1-phenylethanone) represents a typical aldol condensation between two different
carbonyl compounds. The aldol product can subsequently lose a molecule of water (dehydrate) to form
a conjugated ketone:
Whereas the ketone has α-protons and can react with OH- to form an enolate anion,
benzaldehyde cannot do so because it has no α-protons. The aldehyde, however, is more susceptible to
nucleophilic attack by an enolate anion than is the ketone. Therefore, this crossed aldol condensation
can produce a relatively pure product. The reaction mechanism involves base-catalyzed abstraction of
an α-proton of acetophenone, followed by condensation of the resonance-stabilized enolate anion with
a molecule of benzaldehyde:
2
Hiram College, Chem. 320: Spring 2010
The elimination of water from the aldol product occurs in two steps. The first step is the formation of an
enolate anion by base-catalyzed abstraction of an α-proton from the aldol condensation product. The
second is the expulsion of the hydroxylide anion to from the conjugated dehydration product:
Often the dehydration of the initially formed aldol product does not occur spontaneously.
However, dehydration is strongly favored in the reaction that you will be carrying out. the rate of
dehydration is more favorable because loss of hydroxide produces a product with extended conjugation.
this conjugation also influences the equilibrium constant for the reaction, and even more important is
the fact that the dehydration product precipitated from the reaction mixture.
Symmetrical ketones are used for most aldol condensation reactions. Not only does
dehydration occur under the reaction conditions, but a “double condensation” occurs. Two molecules
of an aromatic aldehyde condense with one molecule of a symmetrical ketone to form, after
dehydration, an extensively conjugated product. Using an excess of the aldehyde ensures that a double
aldol-dehydration cycle occurs in the reaction. The double aldol-dehydration cycle that would occur
with 3-pentanone and benzaldehyde follows:
NMR Spectroscopy of the Aldol-Dehydration Product
To characterize your unknown compounds, you need to obtain an NMR spectrum of your aldoldehydration product as well as synthesize solid derivatives of the aldehyde and the ketone. Analysis of
the 1H NMR spectrum will allow you to draw conclusions about the structure of your aldol-dehydration
product and, by deduction, the structures of the aldehyde and ketone you used as starting materials for
the reaction.
The β-proton of a conjugated ketone is more strongly deshielded than the α-proton, even
though the α-proton is closer to the electron withdrawing carbonyl group. This phenomenon can be
understood when the resonance in a conjugated ketone is considered:
3
Hiram College, Chem. 320: Spring 2010
The substantial amount of positive charge at the β-carbon atom strongly deshields the β-proton.
the phenyl group also deshields the proton that is β to the carbonyl group. as a consequence, the βproton (and sometimes even the α-proton) is superimposed on the aromatic protons, and NMR peaks in
the aromatic region can be difficult to assign with certainty. However, it is not difficult to distinguish a
para-disubstitued benzene ring from a monosubstitued benzene ring by NMR analysis.
In addition, the structure of the ketone portion of the aldol-dehydration product can readily be
ascertained by its NMR spectrum. Two of the ketones that are possible unknowns contain cyclohexane
rings, which have axial and equatorial hydrogen atoms that usually have different chemical shifts. An
equatorial hydrogen on a cyclohexane-carbon atom generally has a chemical shift approximately 0.5
ppm greater than an axial hydrogen on the same carbon atom. Although the NMR spectrum of your
aldol-dehydration product may be complex, it will contain valuable information about the structure of
the product and thus indirectly about the structures of your unknown aldehyde and ketone.
You will be assigned an aldehyde and a ketone from the following list as the starting reagents for
your aldol condensation.
Table 1 lists the melting points of the aldol dehydration products formed from these aldehydes
and ketones. The identification of the aldol-dehydration product deduced from these melting points
and from the 1H NMR data must, of course, be the same.
Table 1
Melting points of aldol-dehydration products
KETONES
Acetone
ALDEHYDES
benzaldehyde
113°C
p-tolualdehyde
175°C
p-anisaldehyde 129-130°C
cinnamaldehyde
144°C
Cyclopentanone Cyclohexanone 4-Methylcyclohexanone
189°C
118°C
98-99°C
235-236°C
170°C
133-135°C
212°C
159°C
141-142°C
225°C
180°C
163-164°C
4
Hiram College, Chem. 320: Spring 2010
Arylhydrazone Derivatives of Aldehydes and Ketones
Both aldehydes and ketones usually undergo rapid reaction with arylhydrazines such as phenylhydrazine
or 2,4-dinitrophenylhydrazine:
These hydrazones are normally high melting-point solids, especially in the case of the deeply
colored 2,4-dinitrophenylhydrazones. Their melting points can serve as aids in identifying your starting
carbonyl compounds. Before the advent of modern infared and NMR spectroscopy, the use of solid
derivatives of liquid compounds was widespread in organic chemistry. You will prepare a 2,4dinitrophenylhydrazone derivative of your ketone, and you have the choice of preparing the
phenylhydrazone or the 2,4-ditrophenylhydrazone derivative of your aldehyde. In summary the
following strategy will be useful in your study.
1.
Carry out the aldol condensation and dehydration between an “unknown” aldehyde and an
unknown” ketone.
2.
Obtain the melting point and 1H NMR spectrum of your product.
3.
Prepare the phenylhydrazone or 2,4-dinitrophenylhydrazone of the aldehyde and the 2,4dinitrophenylhydrazone of the ketone and determine the melting points.
4.
Deduce the structure of your aldol-dehydration product and your starting materials by
evaluating the data collected in steps 2 and 3.
5
Hiram College, Chem. 320: Spring 2010
Procedure:
DAY 1
Safety Information:
-Wear gloves while performing the experiment and work in the hood.
-The aldehydes and ketones used in this experiment are skin and eye irritants
-Aqueous sodium hydroxide solutions are corrosive and cause burns.
1.
Obtain a set of unknowns from your instructor. The vials contain enough of each compound for
the aldol-dehydration reaction and the preparation of a derivative.
2.
With a 1-ml graduated pipet, measure 0.8 ml of the unknown aldehyde and place it in a 25-ml
Erlenmeyer flask, (make sure to note the unknown number).
3.
Using another 1-ml graduated pipet, measure 0.2 ml of the unknown ketone and add that
compound to the same 25-ml Erlenmeyer flask.
4.
Add 0.4 ml of 95% ethanol and 3.0 ml of 2M sodium hydroxide solution to the flask. Stir the
solution with a magnetic stirrer for 15 min--or longer, if precipitate is still forming. If the
solution is only cloudy or very little precipitate has formed after 15 min, heat the reaction
mixture in a boiling water bath for 10-15 min. Cool the flask to room temperature.
5.
When precipitation is complete, cool the flask in an ice-water bath for 10 min. While the flask is
cooling, place 8 ml of 95% ethanol in a test tube; repeat this procedure with 4 ml of 4% acetic
acid in 95% ethanol (v/v).
6.
Collect the product by vacuum filtration on a Buchner funnel.
-Disconnect the vacuum and rinse the product with 4 ml of the ice-cold ethanol.
-Reconnect the vacuum and draw the liquid from the product.
-Repeat this washing procedure with the 4 ml of acetic acid/ethanol solution
-Finally wash the crude product with the remaining 4 ml of ethanol
7.
Before crystallizing the crude product, you need to find a suitable solvent
-test 95% ethanol and toluene according to the procedure described in Technique 9.2.
The addition of a few drops of hexane may be necessary to promote crystallization
from a toluene solution.
-If neither of these recrystallization solvents is satisfactory for your aldol-dehydration
product, test 9:1 (v/v) mixture of 95% ethanol/acetone. Once you have selected a
suitable solvent, carry out the recrystallization. Allow the crystallized product to dry
until the next lab period.
8.
Weigh your aldol-dehydration product and determine its melting point. Obtain an NMR
spectrum of your product using deuterated chloroform as your solvent.
6
Hiram College, Chem. 320: Spring 2010
DAY 2
Safety Information:
-Wear gloves while performing the experiment and work in the hood.
-The aldehydes and ketones used in this experiment are skin and eye irritants
-2,4-Dinitrophenylhydrazine is toxic and an irritant. Phenylhydrazine is toxic and a suspected cancer
agent.
Your instructor will advise you about whether you will prepare the phenylhydrazone or the 2-4dinitrophenylhydrazone of your unknown aldehyde. If you are preparing the 2,4dinitrophenylhydrazone, use the same procedure as the on used for the ketone derivative.
Compare the melting point of the phenylhydrazone or the 2,4-dinitrophenylhydrazone of your aldehyde,
whichever you prepared, with those in Table 2. You will need to use your interpretation of the NMR
spectrum of your aldol-dehydration product to distinguish between the two aldehydes that have similar
melting points for the 2,4-dinitrophenylhydrazone derivative.
Table 2
Melting points of phenylhydrazones and 2,4-dinitrophenylhydrazones of Aldehydes
ALDEHYDES
benzaldehyde
p-tolualdehyde
p-anisaldehyde
cinnamaldehyde
Phenylhydrazone MP, °C
158
114
120
168
2,4-dinitrophenylhydrazone MP, °C
237
232
254
255 (decomposition)
Phenylhydrazone of Unknown Aldehyde
1.
2.
3.
4.
Place 4 Pasteur pipet drops of the unknown aldehyde and 0.5 ml of ethanol in a 10 x 75 mm test
tube.
Add water dropwise, shaking after each drop, until the cloudiness produced just disappears (an
indication of saturation). If too much water is used, add 1 or 2 drops of ethanol to give a clear
solution.
Add 4 drops of phenylhydrazine and shake the test tube in an ice-water bath and collect the
phenyhydrazone on a Hirsch funnel by vacuum filtration.
Allow the phenyl hydrazone to dry and then determine its melting point. Compare the melting
point of your derivative with those given in table 2.
2,4-Dinitrophenylhydrazone of Unknown Aldehyde and Ketone
1.
Dissolve 4 Pasteur pipet drops of the unknown ketone in 0.5 ml ethanol in a 10 x 75 mm test
tube.
2.
Add 1.5 ml of the 2,4-dinitrophenylhydrazine reagent solution. Shake the tube to mix the
contents. A precipitate usually forms immediately. Let the mixture stand at room temperature
for 15 min before collecting the solid product on a Hirsch funnel by vacuum filtration.
7
Hiram College, Chem. 320: Spring 2010
3.
Wash the crystals with three 1-ml portions of cold ethanol (to do this, remove the
suction, add the ethanol, and stir the crystals gently to wash them completely. Then
apply suction again.
4.
Recrystallize the 2,4-dinitrophenylhydrazone from ethanol (technique 9.7a). Allow it to dry and
determine its melting point. Compare the melting point of your derivative with those given in
Table 3.
Table 3
Melting points of 2,4-dinitrophenylhydrazones of Ketones
KETONE
Acetone
Cyclopentanone
Cyclohexanone
4-methylcyclohexanone
2,4-dinitrophenylhydrazone MP, °C
126
142
162
134
LAB REPORTS (20 points) -You must have in order:
1) Title (in bold and centered)
2) Objectives-1 pt
3) Procedure -a few sentences, reference where the entire procedure can be found -1 pt
4) Results -must include the overall reactions (draw the structure of your aldol-dehydration product (day
1) and write a balanced equation for its formation, and write the equations for the formation of your
hydrazones (day 2) using the structures of your identified aldehyde and ketone). Show the equation for
percent yield, one sample calculation for percent yield, a table with all obtained percent yields (if only
one product was obtained no table is needed for percent yield), a table for melting points with both
experimental and literature values and reference where it was found, a table with important chemical
shifts from 1H NMR-labeling each shift with it’s characteristic bond, - 6 pt
5) Discussion-discuss the results and explain the percent yield results from the aldol-dehydration.
Explain if the NMR spectrum of your aldol-dehydration product supports the identifications determined
from the melting points. Also explain how the derivatives obtained (MP) further support the identity of
your unknowns. -9 pt
6) Conclusion- be brief, restate results, include error, and provide enhancements for future
experiments-3 pt
8