1

Exp't 17
Mystery Product: The Reaction of Benzaldehyde and Aniline
by Kurt Rublein, Organic Instructional Laboratories, 2/1/95 Revised 6/30/98
PreLab
1. More than one geometric isomer is possible for the imine product. Draw them and predict which one will be most
favored.
2. How could you determine the ratio of the possible products? For that matter, how could you easily separate the different
isomers?
Introduction
Aldehydes and ketones show a high degree of reactivity with respect to nucleophilic attack of the
carbonyl carbon. Ammonia and its derivatives such as primary amines, hydrazine (N
2
H
4
) or
phenylhydrazines (C
6
H
5
NHNH
2
) all react by initially attacking the carbonyl carbon, followed by
hydrogen transfers to give an amine where the nitrogen is bonded to a carbon that also contains a
hydroxy group. Under acidic conditions, the hydroxyl group is protonated, followed by loss of water
R
C
O
R' R
C
O
-
R'
N
R"
H
H
R
C
OH
R'
N
R"
H
R
C
OH2
R'
N
R"
H
R
C
'R
N
R"
H
R
C
'R
N
R"
R' = carbon group, ketone
R' = H, aldehyde
+ NH
2
R"
+
H-B
B
H-B
+
B
"Schiff Base" or also
known as an "imine"
to give the conjugate acid of the observed product. Hydrogen ion transfer then gives the Schiff base
product. The condensation step to give water is acid catalyzed and is the rate-determining step of the
sequence. All of the steps of the above sequence are reversible. In principle, the reaction of water with
the Schiff base will give back the aldehyde or ketone and the amine from which it was formed.
However, here, we are using aromatic reagents, which form products that are more stable than analogous
alkyl-containing reagents. Ketones do not react as readily as do aldehydes.
The Importance of Imines
From a synthetic perspective, imines are important in the syntheses of complicated amines. The Schiff
base can be reduced with hydrogen to give the amine.
From a biological perspective, imines also play an important role in the chemistry of vision: 11-cis-
retinal is bonded to opsin (the entire complex is called rhodopsin) by the formation of an imine with the
NH
2
of an amino acid residue of the opsin protein. The cis linkage of cis-retinal isomerizes when struck
by a photon to form the trans-isomer. The trans isomer does not fit as well in the pocket formed by the
opsin, thus the imine linkage hydrolyzes to give the trans-retinal and opsin. Enzymatic isomerization
gives back the cis isomer, and the cycle is ready to begin again.

H3 C
H3 C
H3 C C O
H
CH3
CH3
H2 N Opsin
H3 C
H3 C
H3 C C N
H
CH3
CH3
Opsin
11-cis-retinal
rhodopsin
2
Precautions
Aniline is highly toxic and is an irritant; it is also an anticipated carcinogen. Avoid breathing fumes or
fumes from solutions that contain aniline. Wear gloves and keep the reaction in the hood at all times.
PreLab
Be sure to include all sections of the PreLab that accompany the Synthetic Experiments. In the Chemical Data Table, you
should include your best guess for the structure of the product. If you are correct, the data for your product is in Aldrich (use
the formula index).
Procedure
Obtain a sample of fresh pure benzaldehyde prepacked in a shorty vial from the hooded shelf or the
stockroom. To a tared 13 x 100 test tube, add 2.05 mmoles of benzaldehyde and 2.00 mmol of aniline.
Add 1.0 mL of ethanol and 3 boiling chips. Add 1 drop of 5% HCl solution. (If it is not available,
make a small amount of your own by mixing 0.1 mL of 10% HCl and 0.1 mL of water.) Gently reflux
the mixture for 1 hr. After 1 hr, let the mixture cool to room temperature. Add 2 mL of water to the
mixture, with stirring. At this point, you should have a medium to very cloudy water layer and a yellow
to brownish-yellow oil on the bottom of the test tube. Warm the solution up gently, just until the upper
aqueous layer becomes rather clear. (This step is designed to remove benzoic acid from the mixture,
which is always present to some degree in benzaldehyde; if it's not removed here, the chance of forming
oils later is greater.) Remove the top layer. Now add 2 mL of ethanol, stir to dissolve the oil
completely, and transfer to another test tube, leaving the boiling chips behind. Use another 2 mL of
ethanol to rinse the first tube and add the rinsing the fresh test tube. Place the tube (which now contains
a total of 4 mL of solution) in an ice water bath for 10 min. Once it is very cold, add one small chunk of
ice (it has to be small to go into the test tube) and scratch the inner wall of the test tube. Keep the tube
chilled and continue to add a few more small chunks of ice. (This step allows the water content of the
solution to slowly increase, rather than the sudden change that occurs when water is added; it also helps
to chill the solution.) Once crystals begin to form, let the mixture stand for another 5 minutes in ice
water. Filter the product using pipet filtration. Wash the solid twice with 1 mL of water.
Recrystallization
The product can be recrystallized with a two solvent system using ethanol and water. This can be
accomplished by dissolving the solid in a minimum amount (the smallest amount it takes to dissolve the
solid) of warm ethanol (heat the solution on a sand bath with a boiling stick.) Once all the crystals have
dissolved, take solution off the heat and while cooling, add water dropwise with intermittent scratching
on the inside walls of the container with a stir rod. Collect the crystals by pipette filtration or on the
Hirsch funnel. Once all the liquid has been removed, dump the pasty solid onto a piece of filter paper
and allow the solid to dry thoroughly before it is weighed, the melting point obtained, and the product
analyzed.
Cleaning Up
Dispose of all filtrates and wastes in the non-halogenated organic waste containers.
Analyses
The product may be analyzed by IR, NMR, or UV-VIS; see your assignment strip for the specific analysis you are assigned.
If you analyze the product by IR, the C=N stretch common to imines appears between 1615 and 1700 cm
-1
; note also that
conjugation will shift the absorbance to lower wavenumbers, just as the case with C=O stretching when the carbonyl is
conjugated.
Questions to be answered in the Final Report
1. Use Aldrich to determine the structure of 1,2-phenylenediamine. Predict the structures of the products that form from the
reactions of one mole of 1,2-phenylenediamine and
a. one mole of benzaldehyde b. two moles of benzaldehyde
2. Use resonance structures of your product to rationalize the decreased wavenumber of absorbance of the C=N stretch of a
conjugated imine.
3
Synthetic Experiment PreLab Grading Sheet
Name(s):
TA:
Date:
PreLab For Exp't # 17
Mystery Product: The Reaction of Benzaldehyde and Aniline
Possible Missed
Points Points
Date, Name, Desk #, Experiment # & Title(abbreviated after 1
st
pg), Section &
TA Name
4
Summary
8
Goals
8
Reactions, structures, conditions, diagrams
14
Completeness of Chemical Data Table(s)
- Include your best guess for the structure of the Mystery product (4 pts)
14
Chromatographic Behavior Comparison
16
Spectral Features Comparison
12
Work-up - Explanation of the product isolation and purification process
12
PreLab Questions
12
TOTAL FOR PRELAB
100
Date Handed in:
General Comments: Total Points:
4
Synthetic Experiment Final Report Grading Sheet
Name:
TA:
Date:
Final Report For Exp't # 17
Mystery Product: The Reaction of Benzaldehyde and Aniline
Possible Missed
Points Points
Name, Date, Experiment Title (abbreviated after 1st page) and every page
numbered
4
OBSERVATIONS and DATA - Overall organization, readability, completeness
8
Data: Weighing data, molecular weights, moles, density, volumes, refractive
index,
Product analysis conditions i.e. gas chromatographic analysis conditions sheet
for GC and/or GC-MS, weight of sample and KBr for IR; solvent and field
strength for NMR; ionization mode for MS;
12
Yield: Show % yield calculations with limiting reagent clearly stated.
Indicators of product purity such as gas chromatograms or TLC, boiling point
or refractive index.
12
RESULTS AND DISCUSSION - Overall organization, readability, completeness 8
Results; Achievement of goals
16
Product Analysis Data: Quality and Interpretation Structures assigned to all
gas chromatogram peaks and structures written on the corresponding mass
spectra from GC-MS. Structure(s) drawn and interpreted on the product
spectrum. Calculate relative %s of isomers, by-products or starting materials
from GC peak areas.
Interpret major MS or IR peaks or all NMR peaks (including impurities).
Explain how spectra confirm product identity.
See Lab Guide Chapter 3, Section 3.4 for guidelines in annotating spectra and
Ch 11 for help with interpretation.
24
POSTLAB QUESTIONS
16
TOTAL POINTS
100
Date Handed in:
General Comments: Total Points: