Experiment 5: Synthesis of a Benzoic Acid

Derivative

Learning Objectives:

The principal aims of this experiment are to use the Grignard reagent as a method of studying
the utility of organometallic reagents in synthesis and to prepare a carboxylic acid by
carbonylation of a Grignard reagent. Students will first prepare and then react an unknown aryl
Grignard reagent with solid carbon dioxide (dry ice). They will isolate and characterize the
resulting benzoic acid derivative to identify the product and the unknown Grignard reagent. This
experiment will:

● enhance students’ understanding of the reactivity of the Grignard reagent.

● enhance students’ understanding of using the acid/base properties of a
carboxylic acid to afford the isolation and purification of their benzoic acid
product by an aqueous workup.
● enhance students’ understanding of spectroscopic characterization methods
and how to interpret spectral data to make conclusions about the structure of
an organic compound.
● enable students to identify an unknown compound based on characterization
data.

Background: Organometallic Compounds and Grignard

Reagents

One of the most important tools an organic chemist has is the ability to form carbon–carbon
bonds. This enables the synthesis of a compound which has more carbon atoms than the
starting compound. Most of the laboratory reactions you have done so far are simple
substitutions (e.g., iodination of salicylamide) or addition reactions (e.g., reduction of camphor).
This experiment is designed to make a new compound having one more carbon in its structure
than the reagent you started with. Accordingly, to achieve that task, you are going to perform a
Grignard reaction, one of the most versatile reactions in organic chemistry.

Grignard reagents were discovered in 1901 by Victor Grignard, who won the Nobel Prize in
1912 for his discovery, and the reagents bear his name. A Grignard reagent is any
organomagnesium halide (RMgX) and is classified as an organometallic compound, which are
compounds that have a carbon–metal bond. Organometallic compounds may have any of a
number of metal elements, but Li, Na, K, Mg, Cu, Zn, Hg, and Pd or other transition metals are
most common. Organomagnesium halide compounds, or Grignard reagents, were the first
organometallic substances to be extensively studied. In the carbon–metal bond, the polarization

of the bond is such that that the carbon is electron-rich and bears a partial negative charge δ–.

As a result of this polarization, one of the characteristic properties of organometallic reagents is

that the carbon atom acts as a nucleophile or Lewis base. In contrast, when a carbon atom is
bonded to a more electronegative element such as a halogen in an organohalide, C–X (X =
halogen), an amine, C–N, or C–O in a carbonyl, the carbon is electron-deficient and acts as a
Lewis acid or electrophile in chemical reactions.

The reactivity of an organometallic compound is highly dependent upon the nature of the
carbon–metal bond, which can be ionic or covalent. Organosodium and organopotassium
reagents are highly ionic and the carbon acts like a powerful base. These reagents react
explosively with water and are pyrophoric (ignite upon exposure to air). Organomagnesium
(Grignard reagents) and organolithium reagents are sufficiently ionic in nature to be strong
carbon nucleophiles and strong bases, yet covalent enough to be soluble in many organic
solvents. These two reagents are widely used in organic synthesis. In recent years the use of
other organometallic compounds, particularly organocuprates and organomercury compounds,
have been widely used in research. However, the very low toxicity of the Grignard reagents
makes them a reagent of choice.
The focal point of the reactivity of the Grignard reagent is its highly polarized C–Mg bond.
Therefore, these reagents are reactive not only toward electrophilic carbonyl carbons as a
nucleophile, but also toward acidic hydrogen (including those in water) in the vicinity as a strong
base. Thus, the Grignard reagent should be viewed as a strong base first, over its well-known
nucleophilicity. Grignard reagents (RMgX) react immediately with acidic hydrogen, if present, to
give corresponding RH (an alkane or aromatic hydrocarbon, depending upon the nature of R
group). Even weak acids such as water, alcohols, phenols, and terminal acetylenes will react
with a Grignard reagent to give the corresponding hydrocarbon, RH. Accordingly, since this side
reaction will only lower the yield, it is important to dry the glassware thoroughly before use in
this experiment.

Reaction of Grignard Reagents

In most instructional chemistry lab courses, Grignard reagents are reacted with electrophiles,
such as the carbonyl carbon of aldehydes, ketones, and esters to form primary (upon reaction
with formaldehyde), secondary or tertiary alcohol products as shown in Figure 1. Esters react
with two moles of Grignard reagent to yield a tertiary alcohol with two of the same R (alkyl or
aryl) group from the Grignard reagent.

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Figure 1. Reaction of Grignard reagents with carbonyl compounds to prepare

alcohol products.
However, Grignard reagents, as nucleophiles, can react with any reagent with an electrophilic
atom. One very simple compound with an electrophilic carbon is carbon dioxide. Nucleophilic
addition of an aryl or alkyl magnesium bromide to carbon dioxide produces an intermediate
carboxylate salt that is converted to a carboxylic acid upon acidification as shown in Figure 2
below.

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Figure 2. Reaction of a Grignard reagent to prepare a carboxylic acid.

This reaction may undergo side reactions, such as the addition of a second equivalent of
Grignard reagent to yield a ketone. The ketone could undergo further reaction with a third
equivalent of Grignard reagent to yield a tertiary alcohol, as shown in Figure 3. The likelihood of
these by-products forming is minimized by the reaction conditions. The low solubility of the
carboxylate salt in ether solvents prevents further reaction of the carboxylate to a small extent.
In addition, the amount of carbon dioxide used in this experiment is approximately a fivefold
excess. This excess, in addition to the slow addition of the Grignard reagent to your dry ice,
ensures that the Grignard reagent is far more likely to react with dry ice than with the

carboxylate salt. Finally, the use of dry ice as the source of CO2 keeps the reaction temperature

very cold (as low as –78 °C). At this temperature, the reaction of a Grignard reagent with the
carboxylate salt has a very slow reaction rate.

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Figure 3. Possible side reactions of the carboxylate salt intermediate in the reaction
of a Grignard reagent with CO2.

After the addition of the Grignard reagent to carbon dioxide is complete, the excess dry ice is
allowed to sublime, and the reaction mixture is reacted with a solution of aqueous acid to yield
the carboxylic acid. The aqueous mixture is extracted with an organic solvent to separate out
the inorganic salts and yield a solution of the product benzoic acid derivative plus any
by-products formed. The possible mixture of product and by-products in the organic phase at
this point is shown in Figure 4.

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Figure 4. The carboxylic acid product and some possible products formed by
over-reaction and side reactions of the Grignard reagent with water.

The product and possible by-products from side reactions of the Grignard reagent with water or
over-reaction of the initial carboxylate product will then be separated by extraction of the
organic solution with a solution of aqueous sodium hydroxide. The base solution will
deprotonate the carboxylic acid to yield the more water-soluble carboxylate salt. The
by-products, however, will remain in the organic solvent. Thus, this extraction serves as a
purification of the carboxylic acid derivative. After separation of the two phases, acidification of
the basic, aqueous extract regenerates the carboxylic acid product which precipitates out of
solution.

Product Analysis

The product of your reaction will be characterized spectroscopically by both IR spectroscopy

and NMR spectroscopy. The IR spectrum will be most useful for you to verify that you have
formed the carboxylic acid product (functional group stretches present at 3550–2500 and 1720

cm−1).

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Figure 5. Different substitution patterns on an aromatic ring.

The 1H NMR spectrum of your product will enable you to fully identify your product. The splitting

pattern and integration of peaks in the aromatic region, at 6–8.5 ppm, will enable you to confirm
your identification of the substitution pattern on your aromatic ring (refer to Figure 5). For
disubstituted aromatic compounds with vastly different groups X and Y, there can be predictable
splitting patterns for the hydrogen atoms on the aromatic ring. Perhaps the easiest to
distinguish is the para-substituted compound which as a result of the symmetry in the
compound would display two doublets with equal integrations. One doublet peak is from the two
magnetically equivalent hydrogens ortho- to group X, and the other double peak is for the two
equivalent hydrogens ortho- to group Y. For a compound with substituents meta- to one
another, there will be up to four distinct signals (some overlap may occur), but there should be
at least one singlet from the proton in between the two groups X and Y on the aryl ring. Lastly,
for an ortho- disubstituted aromatic compound, you would once again see up to 4 signals (some
overlap may occur), but there would be no clear singlet in this case. As your spectra will be

acquired by dissolving your samples in CDCl3, aromatic region is also where the signal for

residual CHCl3 in the deuterated chloroform appears. Therefore, you may see a small singlet at

7.26 ppm from the chloroform. This is not a signal from your sample, nor is it an impurity in your
product.
Once you have determined the substitution pattern on the aromatic ring, your next task is to
identify the substituents themselves. One group will be the carboxylic acid group, and for this
experiment, the other may be a chloro, methyl, or methoxy group. Looking upfield in your NMR
spectrum, in the 2–4 ppm region, the presence or absence of a singlet peak from a methyl
group will enable you to determine if your substituent is an alkyl group or a halogen. The
chemical shift of the peak for the methyl group will enable you to determine if the group is a
methyl or methoxy substituent. Remember that atoms that are closely connected to electron
withdrawing atoms such as oxygen are shifted downfield. Refer to the sections on NMR
spectroscopy in your lecture textbook or on the NMR reference chart on the inside back cover
of your lab manual for more information on interpreting an NMR spectrum.

One final thing to note is that the proton from a carboxylic acid group appears in the 10–12.5

ppm region of the 1H NMR spectrum. This peak is often broad and may be difficult to distinguish

from the baseline in your spectrum. The apparent absence of this signal is common. This is why
your IR spectrum will provide the best evidence for formation of the carboxylic acid group.

Experiment Overview

During this lab, you will prepare an unknown carboxylic acid by reaction of an unknown aryl
Grignard reagent with dry ice.

You will isolate your product by an aqueous workup and save your product to characterize in
the following lab period. You will obtain a mass to determine the yield of your reaction and a
melting point and obtain an IR spectrum. Your sample will also be submitted for characterization

by 1H NMR spectroscopy. You will use your characterization data to identify the product and, in

turn, the identity of the unknown Grignard reagent used.

The Grignard reagent will be prepared from an aryl halide that may have a chloro, methyl, or
methoxy substituent in the ortho-, meta- or para- position, as shown in Figure 6.
 zoom image

Figure 6. Possible unknown Grignard reagents.

SAFETY!

Wear appropriate attire for lab. Goggles should be worn at all times when chemicals and/or
glassware are in use anywhere in the lab. Food, beverages, gum, etc., may not be in the lab.
You must wear gloves for the entire experiment.

Care must be taken with handling dry ice. Prolonged contact of dry ice with skin will freeze cells
and can cause injury similar to a burn. You must wear the insulated gloves when handling
dry ice. the chemical (nitrile) gloves do not afford sufficient protection for handling dry ice
safely.

The hydrochloric acid and sodium hydroxide solutions must be handled carefully. If any
chemicals are spilled on your skin or clothing or get into your eyes, immediately wash the
affected area(s) with running water for 15 minutes and notify your TA. Large spills may require
use of the safety shower.

Dispose of all organic wastes in the appropriate labeled container in the hood as directed by the
instructor. Do not pour anything into the sink!

Green Chemistry
The Grignard reaction provides an excellent example of a chemical transformation that meets
the second principle of green chemistry, which is to maximize the atom economy of the
chemical transformation. What this means is that as many atoms as possible in the reactants
and reagents wind up in the product. In a standard reaction of a Grignard reagent to a ketone or
an aldehyde to yield an alcohol, such as the one shown on the following page, no carbon atoms
are lost.

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Although the preparation of a Grignard reaction can still lead to formation of byproducts (such
as protonation of the Grignard reagent or dimerization by reaction with the alkyl or aryl halide),
the intended transformation is highly economical.

Experimental Procedure

Note that you are working with an unknown reagent which will be provided as a solution in dry
THF for you. You should note the concentration and volume of the aryl halide. Make sure you
record your unknown code. Also note that you should not crush your dry ice until immediately
before you are ready to add the Grignard reagent to your dry ice. While you can weigh out a
small chunk of dry ice (wearing insulated gloves) you should not weigh out the piece of dry ice
you use in the reaction. Obtaining your dry ice too soon will increase the amount of time your
dry ice is exposed to air and will allow for more water to condense on the surface of your dry
ice. This will decrease your yield in the reaction.

Glassware

Obtain a 25 mL round-bottom flask from the drying oven. Make sure that it is clean and dry.
Carefully examine your 25 mL round-bottom flask for the presence of star cracks—none should
be found (if a crack is found, return the flask to the stockroom to obtain a replacement). All
glassware drying must be completed before anyone begins adding THF to the reaction flasks.

Preparation of Grignard Reagent

Set your dried flask into your small beaker. Add 0.25 g magnesium turnings and a stir bar into
the round-bottom flask. Then, immediately take your round-bottom flask (magnesium and all) to
the hood and add 2.5 mL dry THF directly from the auto-dispenser into your round-bottom flask.
Verify the dispensers are set to the correct volume. DO NOT use a graduated cylinder to
measure your solvent, as this increases the risk of exposing your reaction to water or other
contaminants. Then, remove your round-bottom flask from the beaker, and attach the Claisen
head and air condenser to the flask (see Figure 7). Be sure to lightly grease all ground glass
joints when assembling your apparatus. Using excessive amounts of grease is often as bad as
using no grease at all. Use a Keck clamp to ensure the connection to the Claisen head and the
flask is safe and secure.

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Figure 7.

Clamp the apparatus to the bars in your hood directly above your heater/stirrer. Use a
disposable glass pipet to add all of the aryl bromide solution to the reaction flask through the
condenser.
Set the hot plate to 150°C and stir the mixture rapidly. In most instances, the reaction should
initiate once the solvent has begun heating to a gentle reflux for a few minutes. Continue
moderate heating and stirring until the solvent is refluxing and maintain a moderate rate of
reflux throughout the addition of your aryl halide. When the Grignard is formed, the reaction
mixture will turn gray and cloudy.

If your reaction is more resistant to initiating, see your Teaching Assistant for guidance.

During the addition of your alkyl halide, the reaction will warm the solution to the boiling point of
THF (66 °C), but it should not react so vigorously that the solvent is boiled out the top of the air
condenser. (Note if the reaction does become excessively vigorous and you are losing solvent
through the air condenser, you can carefully moderate the temperature with a water or ice-water
bath. But, do not cool excessively.) If the reaction flask does not become very warm with the
added aryl halide and none of the magnesium disappears, stop the addition and seek the
guidance of your Teaching Assistant.

Once all of the aryl halide solution has been added, continue heating the reaction mixture under
gentle reflux for 15 minutes. At the end of the reaction, the solution normally has a tan to chalky
brown appearance and most of the magnesium will have disappeared. Discontinue heating and
allow the mixture to cool to room temperature.

Addition to Solid Carbon Dioxide

After the aryl magnesium bromide mixture has cooled to room temperature, put on the insulated
gloves, take a small chunk of dry ice, and wrap it in a paper towel. Use a hammer to gently
break the dry ice into smaller pieces. You want to obtain an approximately 2 g chunk of dry ice
(about the size of a sugar cube) with a fresh surface unexposed to the air. Place your dry ice
into a 150 mL beaker equipped with a stir bar and slowly pour your Grignard reagent to the dry
ice. Let the mixture stir until all of the remaining dry ice has sublimed.
Then, allow the reaction to stir for about 10 minutes until the solution reaches room
temperature. This step will ensure that most of the dissolved carbon dioxide escapes from
solution. After this time, place the reaction beaker to the ice/water bath on your stir plate. Slowly
add 5 mL of a 6 M solution of HCl to your reaction and allow the mixture to stir for a couple
minutes.

Workup and Isolation of Product

Transfer your reaction solution to your separatory funnel and then rinse out the beaker with 15
mL ethyl acetate. Gently shake the separatory funnel and separate the phases into two
separate beakers. Drain the aqueous phase into a flask and drain the organic phase into a
separate flask. Add the aqueous phase back into the separatory funnel and extract it again with
15 mL of ethyl acetate to ensure you have removed all organic materials from the aqueous
phase and separate the phases again, draining both from the separatory funnel. Combine the
organic phases and return them to the separatory funnel.

Extract your combined organic phases with 5 mL of 3 M solution of sodium hydroxide. Separate
the phases. Do not combine the aqueous sodium hydroxide phase with the acidic aqueous
phase from earlier. Combine the organic phase a second time with an additional 5 mL of 3 M
solution of sodium hydroxide. Separate the phases, and combine the two basic aqueous
extracts. This solution should contain the carboxylate salt of your substituted benzoic acid
product.

To recover your benzoic acid product, add 5 mL of 6 M solution of HCl to the basic solution of
your carboxylate salt. A precipitate should form. Use pH paper to verify a pH of at least 2–3. If
the solution is still basic, or only weakly acidic, add additional HCl, a little bit at a time, until the
mixture is acidic.
Place the beaker containing the now acidic aqueous suspension into an ice/water bath. Obtain
about 10 mL of distilled water in a test tube and cool the water in the ice bath as well. Let these
cool while you assemble a vacuum filtration apparatus.

Collect your product by vacuum filtration. Rinse the filter cake with the ice-cold water. Pull air
through the filter for 5 minutes to further dry your product.

Characterization

After your product has dried, you will obtain a mass of your product, a melting point and an IR
spectrum. The NMR spectrum of your sample will be uploaded to your course LMS page.

Cleanup Procedures

Rinse the round bottom flask with water to remove magnesium shavings. Collect shavings on a
paper towel and transfer the shavings into the solid waste container.

All aqueous solutions should go into the aqueous waste bottle in the hood. The organic solvent
should be put into the organic waste bottle in the hood. Wash all glassware with soap and water
as usual. Rinse the glassware thoroughly with tap water then distilled water. Do a final rinse
with acetone to dry water from the glassware.

AFTER you obtain the melting point and mass of your product next week, discard the rest of
your product in the solid waste container in the hood.

Molecular Modeling in class

Experiment 6: Electrophilic Aromatic
Substitution—The Iodination of Salicylamide

Purpose:

● To perform an electrophilic aromatic substitution and determine the identity of

the major product.

Introduction

One of the most important reactions of aromatic compounds is electrophilic aromatic

substitution. There are numerous electrophiles that react with aromatic compounds by

substitution of an electrophile (E+) for a proton on the aromatic ring. All of these electrophilic

substitutions proceed by a common mechanism which is depicted in Scheme 1. An electron pair

from the electron-rich aromatic ring reacts with the electrophile to produce a carbocation. This
carbocation intermediate is resonance stabilized by the delocalization of the charge around the
ring (Figure 1). In the final step of the reaction, the carbocation loses a proton to re-generate the
aromatic ring, yielding the substituted aromatic compound. Halogenation, nitration, sulfonation,
alkylation, and acylation of aromatic rings proceed by this mechanism.

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Scheme 1. General mechanism for an electrophilic aromatic substitution reaction E.

 zoom image

Figure 1. Resonance delocalization of the cationic intermediate in an electrophilic

aromatic substitution reaction.

Placement of substituents on the aromatic ring affects both the reactivity of the ring and the
location at which substitution is most likely to occur. The reactivity is effected by making the ring
either more reactive (activating groups) or less reactive (deactivating groups) toward
substitution than an unsubstituted ring (benzene). Activating groups, which donate electron
density either through resonance (lone pairs of electrons) or through sigma bonds, make the
ring more susceptible to electrophilic substitution since the resulting intermediate would be
more stable and, therefore, easier to form. (You learned very early on in Organic I lecture that
carbocation stability is increased as the number of electron donating groups on that cation
increase.) Electron withdrawing substituents have the opposite effect.

The electronic nature of a substituent also determines where on the ring, relative to the position
of the substituent, that an electrophile will be added. These directing effects, and the
substituents that cause them, are grouped according to whether they are ortho-, para- directors
(typically activating, electron donating groups) or meta- directors (typically deactivating, electron
withdrawing groups). An exception are the halogens, which are ortho-, para- directing due to the
presence of lone pairs of electrons on the atoms. Halogens can donate electron density through
resonance and therefore direct to the ortho- and para- positions, but are deactivators due to
their electronegativity. Refer to any organic chemistry textbook for a more detailed discussion of
the directing effects of substituents on aromatic rings.
 Directing Groups Examples

Ortho- para- directing activators −OH, −nH2, −OR, alkyl, aryl

Ortho- para- directing deactivators −F, −Cl, −Br, −i

Meta- directing deactivators −CHO, −COR, −CO2H, −CO2R, −Cn,

−nO2

Scheme 2 shows the iodination of salicylamide, the reaction you will perform in this experiment.
Salicylamide has two different substituents. The hydroxyl group is an activating group that
directs to the ortho- and para- positions, while the amide is an electron-withdrawing,
meta-directing group. As part of this experiment, you will predict the site at which substitution is
most likely to occur and then test your hypothesis by analysis of the product you obtain. The

electrophile for the iodination is an iodine cation (I+) which is formed by reaction of sodium

hypochlorite (NaOCl, bleach) with iodide ion. The I+ ion formed in this reaction is a strong

electrophile that reacts quickly in an electrophilic aromatic substitution reaction.

 zoom image

Scheme 2. Iodination of salicylamide.

In addition to predicting the most likely product that will form, you will need to characterize your
final product in order to definitively prove its identity.

The fingerprint region of the IR spectrum, and the region from 700–900 cm−1 in particular,

displays prominent absorptions in aromatic compounds due to C–H bonding. The position of
these absorptions is characteristic for different substitution patterns on aromatic rings.
Therefore, characterization of your product by IR spectroscopy will enable you to identify the
placement of substituents on your product. A summary of IR absorptions for substituted

aromatic compounds are presented in the table below.

Green Chemistry

This experiment was introduced into this course as the result of an in-class assignment in an
upper level chemistry course, CHEM 483 Green Chemistry, in 2018. Students analyzed the
current experiments in the lab curriculum and compared them to alternate experiments that
accomplished a similar transformation. The previous experiment, a nitration accomplished by an
electrophilic aromatic substitution reaction, was more expensive, lower yielding, generated
more waste and was less safe than the iodination experiment. Thus, the introduction of this
experiment into the lab curriculum embodies the principle of the twelfth principle of green
chemistry, as the result of this chemical process is inherently safer than the previous
experiment done in this course.

Experimental Procedure

SAFETY!

in this experiment, you will use and prepare aromatic compounds. Although your starting
material is sold as an over-the-counter drug (analgesic), aromatic compounds, in general, are
considered toxic. Use caution when handling the materials used in this experiment. WEAR
nitrile gloves and appropriate eye protection at all times while in the lab. Salicylamide and
sodium iodide are irritants. Sodium hypochlorite (household bleach) solution and hydrochloric
acid are irritants and are corrosive. Bleach solutions can also emit chlorine gas, which is a
respiratory and eye irritant. Dispense bleach in the hood and keep your test tube with bleach
close to your mini-hood. Avoid contact of chemicals with skin, eyes, and clothing. if any
chemicals come into contact with your skin or clothing or gets into your eyes, immediately and
thoroughly wash the affected area with running water for 15 minutes and notify your TA.

Iodination of Salicylamide

First, prepare an ice and water bath in your 400 mL plastic beaker, which will be used to cool
the reaction flask, and set it near your mini-hood. Label two test tubes, a larger one for ethanol
and the smaller one for bleach, NaOCl, solution. Use the dispensing pumps to obtain 20 mL of
absolute ethanol in the larger test tube and 10.0 mL of the 6.00% NaOCl solution (1.15 M) in
the other. Before using the dispensers, double check that they are set to the proper volume.
Bring the reagents back to your workstation and place them in a beaker near the heater-stirrer
close to the hood intake.

Measure out approximately 1 g of solid salicylamide (record the mass in your notebook to the
same number of digits reported by the balances). Add the solid to a 125-mL Erlenmeyer flask
equipped with a stir bar. Add the ethanol previously obtained to the solid in the Erlenmeyer flask
and gently stir using the hot plate/stirrer to aid in dissolving the solid. Remember to clamp your
flask. It may take a few minutes to completely dissolve the solid. If needed, warm the flask with
your hand to speed up the dissolution, DO NOT turn on the heat on the hot plate-stirrer. Ensure
that salicylamide is completely dissolved and the solution is homogeneous before you add the
next reagent.

Measure out approximately 1.2 g (again, record the exact mass in your notebook) of solid
sodium iodide, NaI, and transfer the solid to the solution of salicylamide in ethanol. Stir the
reaction mixture slowly until the solution is again homogeneous.

Once the solution becomes homogeneous, cool the mixture by placing the reaction flask in the
ice/water bath. When your reaction mixture is cooled to 0 °C (this will take about 5 minutes),
remove the Erlenmeyer flask from the ice/water bath and clamp the cold Erlenmeyer flask back
on the heater-stirrer. Quickly add the 10.0 mL of the 6.00% NaOCl solution using a Pasteur
pipet. Stir the flask vigorously to completely mix the contents. The solution will undergo a series
of color changes. Record the colors you observe in your laborarory notebook pages. When the
solution reaches a faint, pale yellow color, the reaction is complete (typically, this takes less
than five minutes). When the pale yellow color appears, turn off the stirrer and allow the
reaction vessel to sit on the benchtop undisturbed for 10 more minutes.

While waiting, obtain 10 mL of 10% (w/v) sodium thiosulfate solution in a labeled test tube and 6
mL of 10% HCl in a second labeled test tube. After the 10-minute waiting period has finished,
carefully add the sodium thiosulfate solution to the reaction solution using a Pasteur pipet. Stir
the flask until the contents are thoroughly mixed. Next, acidify the reaction solution by slowly
adding 10% HCl. Monitor the acidity of the solution (pH) using alkacid papers. You may not
need to add the entire volume of HCl obtained to achieve an acidic solution. As you add the
acid, you will notice a white solid beginning to form in the reaction vessel. At this point, the pH
of the solution is near neutral. Continue adding 10% HCl, but carefully monitor the acidity.

Product Isolation and Purification

Collect the solid product by vacuum filtration. Use a plastic stir rod to carefully press the solid
product in the Büchner funnel; then wash the solid three to four times with 10 mL portions of
cold water, followed by 10 mL of cold absolute ethanol. Weigh this crude product and then
transfer to a 50 mL Erlenmeyer flask, add about 10 mL of absolute ethanol, and heat on the
heater-stirrer until the solvent is boiling (Note: Do not heat so vigorously that the ethanol
evaporates). Add small amounts of ethanol as necessary to dissolve the product in a minimal
amount of hot absolute ethanol. When all solid is dissolved, remove the flask from the
heater-stirrer, and allow the solution to cool slowly without disturbing the flask. After the mixture
has cooled to room temperature, cool it in an ice bath for about 15 minutes to ensure maximum
crystallization of your product. Collect the recrystallized product by vacuum filtration. Wash the
filter cake with additional 10 mL of ice-cold ethanol. Allow the crystals to remain on the filtration
funnel with air being drawn over them for 20 minutes to speed up the drying process.

For your product, obtain a mass (yield) of your product and characterize it by melting point, and

obtain an IR spectrum. Be sure to carefully label all peaks between 700–900 cm−1 on your

spectrum.

In your post-lab write-up, identify your product, discuss how you identified the substitution
pattern on your product (i.e., explain how you know you did not get a different product isomer),
discuss whether or not the iodination product you predicted was correct, and discuss how the
directing effects groups of each substituent on salicylamide led to the formation of this product.
Cleanup Procedures

Be sure to dispose of all liquid waste in the liquid waste container in the hood; this includes any
liquids generated by the washing of your product, and any excess ethanol, 1 M hydrochloric
acid, sodium thiosulfate, or bleach. Be sure to place any excess salicylamide or sodium iodide
in the solid waste container in the hood. It is proper laboratory courtesy to wipe off your work
area with a damp paper towel. Discard the paper towels in the solid waste container in the
hood.

Reference

Eby, E.; Deal, S. T , J. Chem. Ed. 2008, 85, 1426-1428.

Acknowledgements

Thanks are extended to Dr. Michael Nippe and his CHEM 483 course for their analysis of the
environmental impact of the experiments in CHEM 238. Their analysis led to the identification of
the iodination of salicylamide as a greener and safer experiment on electrophilic aromatic
substitution reactions.

Experiment 7: Reactions of Aldehydes and

Ketones

Purpose:

● To study the reactions of aldehydes and ketones and identify an unknown

based on its physical properties, reactions, and spectral data.
Introduction

Organic chemists spend a vast amount of time and effort trying to duplicate and modify
reactions that occur in nature. While living organisms have enzymes that are specifically tooled
to produce a single product, chemists must use carefully chosen starting materials and selective
reagents, often in multistep syntheses to accomplish the same transformation. Aldehydes and
ketones are key intermediates for both in vivo and in vitro synthesis. Aldehydes differ from
ketones in that they have a hydrogen attached to the carbonyl carbon. This carbonyl is easily
oxidized—providing a simple classification test to distinguish aldehydes from ketones. These
two functional groups can readily be interconverted to virtually any other functional group. Most
organic syntheses have at least one step involving an aldehyde or ketone. Moreover, the
carbonyl group figures predominantly in most carbon–carbon chain building reactions (e.g.,
organometallic additions, aldol condensations, etc.).

Prior to the development of more sophisticated analytical instruments like FTIR, NMR, and MS,
most compounds were identified by a laborious process of elemental analysis and selective
chemical degradation with the isolation and identification of the smaller products produced. As
previously stated, aldehydes and ketones undergo a wide variety of reactions. Many of these
proceed with an obvious color change and/or production of a precipitate. Depending upon the
reaction, many of these precipitates have sharp melting points and can be used as qualitative
tests to help identify the unknown material. Formation of these derivatives and their
characterization enabled more than one data point to be collected to confirm the identity of a
compound. Recall from one of your first experiments in 237 (“Who Has My Compound?”) that

no single test result (melting point, solubility or Rf by TLC) was enough to identify your

unknown, but the combined results enabled more definitive identifications. Many of these
chemical characterization reactions are still used as simple tests in forensics labs and in
medical diagnostic tests. The availability of modern spectroscopic methods such as IR and
NMR, and also mass spectrometry, has enabled much more rapid and definitive proof of the
structure of organic compounds.
Identification of an Unknown

In this experiment, you will use a combination of typical reactions of aldehydes and ketones
along with spectral data to identify an unknown. You will be given about 6.5 g of an unknown
sample. Based upon its physical properties, chemical reactions, and spectral data, you will be
asked to identify this unknown. Your ability to successfully complete this task will depend upon
how easily you can put together the pieces of the puzzle. Be aware that like many of the
high-profile forensic cases, laboratory contamination (especially with acetone) can invalidate
your results and make your task much more difficult. (Tables 1 and 2 list the possible aldehydes
and ketones used in this experiment, and their boiling points.)

Physical Properties

When you get your unknown, you should immediately begin recording your observations. (The
first thing you record should be the code associated with your unknown. This should be
obvious, but it is often forgotten.) Note the physical appearance of your unknown. Is it a liquid or
a solid? What does it look like (free-flowing or viscous liquid; powder, needles, platelets, etc.)?
Is it colorless or colored? Is it transparent or not? Is the unknown water soluble? Older texts
would suggest that you smell your compound (a very bad idea). Volatile aldehydes and ketones
tend to be pleasant-smelling liquids. Aldehydes are frequently described by fragrance chemists
as having a “sharp note as an afterthought of their bouquet” (smells are described like musical
chords). All of these compounds are considered to be irritants—even those responsible for the
fragrance and flavor of foods.

It may be very difficult, but resist the temptation to jump to any conclusions about your
compound. it is quite easy to bend observations to fit a preconceived notion. this biased
approach can lead to misinterpretation of the results and is commonly described as “eye strain
and over anticipation.” Gather, and then interpret, the data. if two tests lead to conflicting
conclusions, repeat the tests to confirm or disprove the previous results. it may even be
necessary to run additional tests to resolve conflicting data.
You also need to record other physical data for your compound. If your sample were solid, you
would need to obtain a melting point for the crude and the recrystallized material. On the other
hand, if your compound is a liquid, a boiling point can be a valuable data point. There are
several methods for determining the boiling point of a liquid, but since it would be a good idea to
purify your material before running these tests and making derivatives of it, you can measure
the boiling point of your compound while distilling it.

Solubility is a very easy property to determine. You will need this information before running a
few of the qualitative tests, so you may as well do it early in your examination. For this, put
approximately 5 mL of water in a clean test tube and add a drop or two of your liquid sample (or
~ 100 mg of a solid sample) to the tube and “shake” gently. If you are unfamiliar with this
technique, grasp the upper portion of the tube in one hand and shake the bottom of the rube
rapidly from side to side. This can also be accomplished by using your other hand to “strum” the
bottom of the tube (similar to strumming a guitar). If the material disappears, it is soluble. If it
does not, it is, at the very least, not infinitely soluble. Do not use a stopper (or your finger) to
plug the tube for shaking— your material can adhere to this foreign organic material and lead
you to believe your compound is water soluble when it is not.

There are two things that can go “wrong” when distilling your unknown. First (and most often
encountered), since the temperature you measure for the boiling point is dependent upon the
positioning of the thermocouple or thermometer, the temperature you observe may be as much
as 10 °C off. Use the boiling point as a rough estimate and do not immediately eliminate any
compound from the list that boils within approximately 10 °C of your recorded value. Second,
saturated aldehydes have a bad tendency of oxidizing when distilled (or heated) in air (Murphy’s
Law applies here). This can transform some of your impure aldehyde into the corresponding
carboxylic acid. To put it mildly, this acid stinks. Minute traces of the carboxylic acid may be
responsible for the “sharp residual note” associated with the smell of these aldehydes. The
smells of volatile carboxylic acids range from the distinctive odor of rancid socks, to wet goats,
to fresh vomitus—which underscores why smelling these unknowns is a bad idea. Needless to
say, it would be a good idea to save some of your starting material, just in case.
You should obtain the FTIR of your purified sample. The presence of a strong peak in the 1690
to 1740 wavenumber region indicates the presence of an aldehyde or ketone carbonyl group. If
you have an aldehyde, the secondary peaks just below 2900 wavenumbers may also be
evident. In the worst-case scenario, the IR should also tell you if your unknown has
decomposed into a carboxylic acid (strong hugely broad absorbance from ~3500 to 2500
wavenumbers and shifted C=O band). After you finish the experiment and have tentatively
identified your unknown, you can confirm your results by comparing your spectrum with a
reference spectrum of that compound. Note: You will need to find the reference spectrum using
www.ChemSpider.com or Google “compound name IR spectrum.” Another useful place to find
reference spectra is on the Spectral Database for Organic Compounds, SDBS. This site can be
found most easily by searching for “SDBS” in any internet search engine.

Qualitative Tests

Qualitative tests are performed in order to identify the functional groups that are present in an
unknown compound. Even though you were told that you have an aldehyde or ketone and have
confirmed this by IR, you will run standard aldehyde and ketone qualitative tests. Typically, you
will use only a drop or two of your sample for each qualitative test. This portion of your sample
is “lost.” IR is an excellent method for the nondestructive identification of functional groups and
has eliminated the need for many of the standard qualitative tests. Unfortunately, it takes lots of
practice and experience to be able to ferret subtle information from an IR spectrum that can be
easily gathered and confirmed by simple qualitative tests.

Qualitative tests yield either an obvious color change and/or the formation of a precipitate. For
this experiment, you will also be using a known material to demonstrate what a positive test
looks like. These known materials were chosen because they give a strong positive result. No
test is infallible, and false-positive (and false-negative) results can occur. If your test results
conflict with your identification, either rerun the test or choose an alternative qualitative test to
clarify the discrepancy. After you have carried out a few qualitative tests and collected some
physical data, it should be possible to narrow the structure of the unknown to a few possibilities.
Additional tests and derivatives should then be chosen to distinguish between these possibilities
and to confirm previous positive tests.

You will carry out three qualitative chemical tests on your unknown. These are the Tollens’,
Schiff’s, and iodoform tests. Tollens’ reagent and Schiff’s reagent, both mild oxidizers, are used
to identify aldehydes. Finally, the iodoform test detects a methyl group attached to the carbonyl
carbon.

Acetone is a solvent that is commonly used to clean glassware. It gives strong positive results
for many of the aldehyde and ketone classification tests. Fortunately, it is relatively easy to
eliminate this problem when dealing with aldehydes and ketones. None of the classification
tests used in this experiment are hurt by traces of water. If you use acetone to clean your
glassware, rinse the glassware with water to remove the acetone.

Iodoform Test (Haloform Test)

The iodoform test gives positive results for compounds with a methyl group attached to the
functional carbon in methyl ketones and in primary (1°) or secondary (2°) methyl carbinols. The
test solution is iodine dissolved in aqueous base. This solution contains the oxidizing agent,
hypoiodite ion. If the compound is a methyl carbinol, the first step is the oxidation of the alcohol
to a methyl carbonyl (3° alcohols do not oxidize). Ethanol, a 1° methyl carbinol, is oxidized to
acetaldehyde, which produces a strong positive iodoform test. Ethanol is the only 1° alcohol to
produce a positive iodoform test. Acetaldehyde is the only aldehyde to produce a positive
iodoform test. (This fact stated, the further discussion will refer to “methyl ketones” with the
understanding that you recognize that acetaldehyde does the same thing.) The methyl group
attached to the ketone is then iodinated three times under basic conditions to give a
triiodomethyl ketone. In the next step, nucleophilic attack of hydroxide ion at the carbonyl
carbon leads to a tetrahedral intermediate that then loses a triiodomethyl carbanion. This anion
is a relatively good leaving group with the negative charge stabilized by the three halogen

atoms. The carbanion then abstracts a “proton” from water (or the RCO2H formed) to yield
triiodomethane or iodoform. This is visible as a bright yellow precipitate (iodoform or
triiodomethane). This precipitate has a sharp sweet antiseptic smell. Iodoform was widely used
as an antiseptic before the discovery of antibiotics.

This test is also known as the haloform reaction and can be run with chlorine water (chlorine
gas in water) or bromine water. For these two instances, chloroform and bromoform are
produced. These are liquids and will collect on the bottom of the test tube.

Note: Acetone produces a strong positive response for the iodoform test. Rinse the
test tube with water before you start this test.

zoom image

Figure 1.

Schiff ’s Test

Rosaniline hydrochloride is a triphenylmethane dye. It is also known as the dye Acid Violet 19
(named after the color) or acid fuchsin. The amino groups and imine cause the color of this dye
to be wine colored (deep bluish violet to deep-purple). The extended conjugation causes the
compound to strongly absorb in the visible spectrum. The color you see is due to the
reflectance of the light from the blue-purple end of the visible spectrum. When rosaniline
hydrochloride reacts with sodium bisulfite, the central carbon is sulfonated. This destroys the
conjugation between the rings and the resulting product is colorless. This lightly colored solution
of the addition product between rosaniline hydrochloride and sulfur dioxide is called Schiff’s
reagent. Aldehydes react with sulfonate group on the Schiff’s reagent to form the bisulfite
addition product of the aldehyde and result in the removal of the sulfonate from the reagent.
This reaction reestablishes the colored conjugated system, and this is considered a positive
test. There is some evidence that the aldehyde and sulfur dioxide condense with the amino
groups on the rosaniline and this leads to the various colors produced. And this is considered a
positive test.

An important fact to emphasize is that all carbonyl compounds react with sulfur dioxide. Schiff’s
test is primarily used to distinguish between aliphatic and aromatic aldehydes. Aliphatic
aldehydes produce an almost instantaneous color change to wine-purple colors.

Note: You will be running a side-by-side comparison with an authentic aliphatic

aldehyde so you can get a fairly good idea of the time required for this change)

Ketones and aromatic aldehydes also react with Schiff’s reagent to produce an identical color
change, albeit at a much slower rate, at room temperature. Aromatic ketones do not react with
Schiff’s reagent even with warming. A few other compounds besides aldehydes give light pink
colorations, but these colors lack the blue (purple) cast characteristic of carbonyl compounds.
 Note: If you are red-blue color blind, get someone to read your assay for you,
although a deeply tinted solution is indicative of a positive test.

zoom image

Figure 2.

Tollens’ Test

This test takes advantage of the relative ease of oxidation of an aldehyde to a carboxylic acid.
Tollens’ reagent is silver(I) nitrate dissolved in aqueous ammonia (aqueous silver ammonia
complex). This reagent is reduced by aliphatic and aromatic aldehydes to silver(0) and the
aldehyde is oxidized to the carboxylic acid. The silver, reduced from the +1 state to elemental
silver, deposits on the inner surface of the test tube and forms a mirror. Therefore, the Tollens’
test is also known as the silver mirror test. Tollens’ test is negative with ketones because silver
ammonia complex is too mild an oxidizing agent to oxidize the carbon-carbon bonds of ketones.
As always, there are exceptions to this general rule. Ketones with an α-hydroxy group and
some conjugated ketones which exist predominantly as the enol form of the tautomer can give a
false positive Tollens’ test.
 zoom image

Figure 3.

NMR Spectra

This may be the first time that many of you look at “real” NMR spectra and have to determine an
unknown. So there are a few things that can help you decipher the data within these spectra.

Your spectra will be obtained by dissolving your sample in deuterated chloroform (CDCl3). In

your proton spectrum, you will likely see a small signal just downfield of 7.2 ppm. This is from

the solvent your sample was prepared in (>99% CDCl3 with a trace of CHCl3). It is not part of

your unknown. In addition, the important signals for your unknown are integrated and have the
chemical shift given. The integrations are not going to be perfect whole number values. An
integration of 1.94 is almost certainly a signal from two hydrogen atoms. Similarly, an integration
of 3.19 is likely a signal derived from three hydrogen atoms. Finally, some samples will have
signals with complex splitting and/or overlapping signals. The multiplicity of these signals may
be difficult to determine. In those cases, rely on chemical shift and integrations for assignments
or identification of your unknown.

The utility of the 13C NMR spectrum is that it provides a “count” of the number of unique

carbons in your unknown. Just as with the proton spectrum, you will see a signal from the

solvent in your 13C spectrum. This time, however, it will appear as a cluster of three signals right

around 77 ppm. Why is it three signals when there’s only one carbon in CDCl3? Good question!

Unfortunately, the answer is beyond the scope of what you are expected to know at this level.
Just don’t let these signals mislead you into thinking that your unknown has three more carbon
atoms than it actually has. Additionally, remember that you know that you have an unknown that
is either an aldehyde or a ketone; the tests done during lab and also the IR spectrum confirmed
this. Therefore, your sample will have a signal from the carbonyl carbon in the downfield region

of your 13C spectrum. In most cases, this signal will have a chemical shift label. However, on

occassion, this signal may be too low for the automatic data processing software to pick it up.
This is a real signal. Pay attention to it, discuss this signal in your post-lab assignment and
report an approximate chemical shift. The inability to get the exact chemical shift is a software
issue.

Experimental Procedure

SAFETY!

Wear gloves when performing the qualitative tests. A lot of the aldehydes and ketones are considered to
be irritants. All of the reagents used in this laboratory experiment are irritants. Many are also corrosive
and/or toxic. Make certain that your apparatus and various tests are run under the student hood at your
workstation.

Tollens’ reagent should be prepared just before it is used—it will form an explosive precipitate if it is
allowed to stand (several hours to days are required for this). the silver nitrate solution is both toxic and
will cause unsightly stains on whatever skin comes in contact with the solution. the nitric acid used to
clean the silver mirror from the test tube is a corrosive toxin. it will produce strong yellow stains if it comes
in contact with your skin. Wipe up any spills, rinse with copious quantities of water, and then rinse the area
with aqueous bicarbonate solution.

the iodoform test makes use of 6 M naOH. the sodium hydroxide solution is highly corrosive. Aqueous
strong alkali solutions are particularly hazardous to the eyes. take care when handling the solution. the
iodine water (aqueous iodine) solution does give off a low level of iodine vapor. Prolonged inhalation of
iodine vapor can lead to permanent sinus problems. iodoform (a solid) is considered to be a cancer
suspect agent; do not breathe the vapors. Dispose of the iodoform in the appropriate container in the
hood.
Schiff’s reagent is considered to be a corrosive irritant. Triphenylmethane dyes are considered to be
mutagenic (carcinogenic) because they cause tumors at the site of injection—but they are not absorbed
by mammalian systems. the “release” of sulfur dioxide by Schiff’s reagent is responsible for the corrosive
irritant tag. Rinse exposed areas with water.

Distillation

Transfer the unknown aldehyde or ketone to a 25 mL round-bottom flask, add 2–3 boiling chips to the
flask, and set up the apparatus for a microscale simple distillation. (See the apparatus in the on-line
manual.) Lightly grease all ground glass joints before assembling the glassware. Center your distillation
setup under your hood to minimize the escape of any vapor into the laboratory. Carry out a simple
distillation to purify the unknown and to determine the boiling point. When the temperature appears to
reach a constant value, transfer the first fraction with a Pasteur pipet to a capped sample vial. Now collect
the principal fraction and record the boiling point range for the unknown. Transfer the principal fraction to
another clean sample vial with a Pasteur pipet. Cap the vial to minimize exposure to any irritating vapors.
Some of the samples may contain significant quantities of higher boiling impurities. Stop the distillation if
the temperature begins to fall or to rise rapidly, indicating that the principal fraction has distilled, or if there
is only 1 to 2 mL of liquid remaining in the distilling flask. For safety reasons, never continue a distillation
until the distilling flask is dry.

Infrared Spectrum and Solubility

Use a few drops of the principal fraction to determine the infrared spectrum. Also test the solubility of your
unknown in water.

Note: Remember to record the code on your unknown onto your laboratory report.

The Tollens’ Test

Thoroughly clean two test tubes with soap and water. If the tube is not clean, the silver will not deposit on
the inner surface as a mirror, but will appear as a black precipitate. Make a warm water bath using a
beaker with water on the heater-stirrer at a setting of 5. Add two mL of a 5% aqueous solution of silver
nitrate and two drops of 3 M sodium hydroxide to the test tube. Mix the contents of the test tube
thoroughly. A precipitate of silver oxide or silver hydroxide will form in the tube. Add dilute ammonium
hydroxide solution to the test tube drop by drop, with shaking and swirling, until the precipitate just
dissolves. Add two drops of the carbonyl compound to the test tube. Mix the solution by shaking and
warm gently with a water bath. A positive test is the formation of a silver mirror (if the test tube is very
clean). The formation of a black precipitate is also considered to be a positive test—any impurity in the
tube will minimize mirror formation and cause the silver precipitate to be suspended in the solution (it
appears black). Carry out the Tollens’ test on your unknown aldehyde or ketone and then on a reference
aldehyde provided for comparison purposes.

Cleanup! The silver mirror must be removed from the glass surface by rinsing with dilute nitric acid.

The Schiff’s Test

Perform the test on your unknown and a sample of 2-methylpropanal or other aldehyde. Add three drops
of the unknown to 2 mL of Schiff’s reagent. Do not warm the mixture. Aldehydes give a wine-purple color
within 10 minutes (actually, the color change is almost immediate). (If you are red-blue color blind, get a
neighbor to read your test. Typically, you will notice the solution darken even if you cannot distinguish the
color.) You may have two layers, with only one being colored. Aliphatic aldehydes and aldose sugars
(those with an aldehyde rather than a ketone) react with this agent rapidly and produce an almost
immediate color change. Aromatic aldehydes, aliphatic ketones, and ketose sugars (those with a ketone
rather than an aldehyde) produce this same color change much more slowly. This is why it is important
not to warm the reaction, otherwise you will not see the difference in reaction time. Other compounds,
either because of their pH or the presence of other functional groups, can cause this dye to produce a
pinkish solution. Remember, a positive test is an immediate vivid color change.

If your unknown has not produced a color change by the time the test tube treated with 2-methylpropanal
has become wine colored, you can feel fairly confident that your unknown is not an aliphatic aldehyde.

The Iodoform Test

You will need to know if your compound is water soluble before running this test. You will perform the
iodoform test on your compound (or a solution of your compound in dioxane) and on 2-butanone (methyl
ethyl ketone) for comparison purposes. (Warning! Traces of acetone on your glassware will provide a
dramatic positive test.)

Add 1 mL of 6 M NaOH to a test tube containing 5 mL of water. If your compound is water soluble, add
five drops of the compound to the solution. If your compound is not water soluble, mix five drops of it with
2 mL of dioxane (a water soluble ether) and add this to the solution. To this alkaline solution of the
carbonyl compound, add the iodine–potassium iodide solution dropwise until the brown color is no longer
discharged and the solution is light yellow. If the test is positive, a yellow precipitate of iodoform will
appear.

NMR Characterization

Return the rest of your sample in your section’s storage drawer labeled with your section number and your
unknown code (e.g., “505-A” for section 505, unknown A).

1 13
Both H and C NMR spectra will be obtained and processed for you. A .pdf file (with the code for your

sample) of these spectra will be posted on your course LMS page approximately one week following the
experiment.

For the lab report, the NMR spectra need to be labeled and annotated (similar to how your IR spectra are
labeled) to indicate the structure and atom assignments. The analysis of your data should include a
1 13
discussion/interpretation of your functional group tests along with the IR, H, and C NMR spectral data.

Cleanup Procedures

Discard all solutions in the appropriate containers in the hood. Make certain that you do not place the
waste in the wrong container. Discard any filter paper in the container labeled for this solid waste in the
hood. It is common courtesy to use a damp towel to wash your workstation area (make certain to clean
the area under the bench overhang at your station). Traces of these agents are not only capable of
causing holes in whatever apparel (or skin) that comes in contact with them, but also quite toxic. Place
used gloves in appropriate waste container.

Name of Compound Boiling Point (°C)

2-Propanone 56

2-Butanone 80

3-Methyl-2-butanone 94

3-Pentanone 102

2-Pentanone 102
2,2-Dimethyl-3-butanone 106

4-Methyl-2-pentanone 117

2,4-Dimethyl-3-pentanone 124

2-Hexanone 128

4-Methyl-3-penten-2-one 130

Cyclopentanone 131
4-Heptanone 144

5-Methyl-2-hexanone 144

3-Heptanone 148

2-Heptanone 151

Cyclohexanone 156

6-Methyl-3-heptanone 163
5-Methyl-3-heptanone 160

2,6-Dimethyl-4-heptanone 168

2-Octanone 173

Acetophenone 202

Benzyl methyl ketone 216

Propiophenone 220
2-Undecanone 228

Name of Compound
Boiling Point (°C)

Propanal 49

2-Methylpropanal 64

Butanal 74
3-Methylbutanal 93

2-Methylbutanal 93

Trichloroethanal 98

Pentanal 103

Hexanal 131

Heptanal 153
Furfural 161

3-Cyclohexene-carboxaldehyde 165

Benzaldehyde 179

Phenylacetaldehyde 194

Salicylaldehyde 197

o-Tolualdehyde 200
 p-Tolualdehyde 204

Citronellal 207

Discussion Items for the In-Lab Notebook

Record this data in your laboratory notebook. Use the following as a guide for your data entry.

RECORD YOUR UNKNOWN CODE: _________________________

Distillation: Boiling Point:

Infrared Spectrum (attach copy)

Test Result

iodoform
Schiff’s

tollens’

Compound Boiling Point

Experiment 8: Derivatives of Carboxylic
Acids

Purpose:

● To conduct a preparative scale synthesis, isolation, and characterization of

an ester.
● To examine the reactions of an acid chloride with water and ammonia.

Introduction

Carboxylic acids and their derivatives are widely encountered in nature. Primary alcohols,
aldehydes, and carboxylic acids differ only in their oxidation state. Common derivatives of
carboxylic acids include esters, carboxylic acid anhydrides, acid chlorides, and amides.
Hydrolysis of these derivatives yields the starting carboxylic acids. Esters are encountered as
fats, oils, waxes, fragrances, and solvents. A few naturally occurring acid anhydrides are
known; these are also used in industry in synthetic applications. Carboxylic acid halides are
synthetic intermediates used in synthesis. Amides are encountered as enzymes, protein,
coatings (urethanes), and as solvents.

zoom image

Figure 1.

The chemical industry has been under tremendous pressure from environmentalists to eliminate
the use of chlorine and chlorides. Although the chemical industry maintains that should this
happen, there would still be no detectable change in the worldwide level or production of
polychlorinated biphenyls (PCBs) or dioxins, the industry is now using carboxylic acid
anhydrides and mixed anhydrides in the place of acid chlorides for many synthetic applications.

There are countless methods and variations on these methods for the synthesis of esters.
However, if the starting acid is readily available and the synthetic target is the methyl, ethyl, or
propyl ester of said acid, then the Fischer esterification is the method of choice. The Fischer
esterification is an equilibrium process in which the carboxylic acid is mixed with an excess of
the alcohol and a trace of mineral acid acts as the catalyst. The reaction mixture is generally
heated to increase the rate of reaction. The problem is that once an equilibrium is obtained, no
additional product is formed, regardless of further heating. Two steps can be taken to drive the
reaction toward completion.

The first is to use an excess of the alcohol (methyl, ethyl, and propyl alcohol are inexpensive).
This also serves nicely as a solvent for the reaction. Second, if at all possible, one or both of the
products can be removed as it is formed to drive the reaction to completion.
The removal of water is the easiest way to drive a Fischer esterification to completion.
Unfortunately, unless the ethyl or propyl esters are being synthesized, removal of water is very
difficult. Ethanol, n-propyl, and isopropyl alcohol each form azeotropes with water, allowing
them to be easily removed during the reaction. Methanol does not form an azeotrope with
water, but distills at a temperature below 100 °C.

The first step in the Fischer esterification is the protonation of the carbonyl oxygen of the
carboxylic acid. The protonated acid then undergoes nucleophilic attack at the carbonyl carbon
by a molecule of the alcohol to produce a tetrahedral intermediate. Following proton transfer,
the tetrahedral intermediate collapses with the loss of water to form the ester. The forward
reaction is known as esterification. The reverse reaction, the hydrolysis of the ester to form the
carboxylic acid and starting alcohol, follows this same mechanism. Adding excess water drives
the reaction toward hydrolysis.

Acid chlorides, carboxylic acid anhydrides, esters, and amides possess greatly different
reactivities toward nucleophilic acyl substitution. Alkyl acid chlorides show a very exothermic
reaction with water. (The smaller the molecule, the more violent and rapid the reaction.)
Aromatic acid chlorides are less reactive, but will react slowly with water at room temperature.
Carboxylic acid anhydrides are reactive derivatives of carboxylic acids, but generally are less
reactive than the acid chloride. As neutral compounds, these do not react with water and
frequently require an acid catalyst to initiate the reaction. Mixed anhydrides, particularly those
with formic acid, are similar in reactivity to the acid chloride. Esters, on the other hand, are
relatively inert to water, as demonstrated by most oils and waxes. For an ester to show an
appreciable rate of hydrolysis, a mineral acid catalyst must be present and generally the
temperature must be elevated. Amides are even more resistant than esters to hydrolysis.
Elevated temperatures, acid catalysis, and extended reaction times are normally required to
produce hydrolysis of amides. (Note: Biological amides include hair and skin which are
remarkably inert. Their pigments are not amides and are much more easily altered.) Esters and
amides can also be hydrolyzed under basic conditions (saponification).
You encounter carboxylic acids and their derivatives on a daily basis, especially in the kitchen
and with food. For example, the legal definition of a fat is a “triglyceride.” triglycerides are the
triesters of glycerol (1,2,3-propanetriol or glycerin) and three carboxylic acids. Oils are liquids at
room temperature; fats are solid or semi-solid at room temperature. the law does not make this
distinction. Partial hydrolysis of fat (triglycerides, liquid or solid) yields mono- and diglycerides
(one or two esters on the glycerol molecule). Mono- and diglycerides have exactly the same
calorie count per gram and metabolize as fats (triglycerides). However, by legal definition these
are not “fats” and therefore do not show up on the nutrition box required on most food items. the
calorie count does reflect the calories from the food item per serving (note size) regardless of
these legally “hidden” fats.

Acid chlorides are frequently used as intermediates for the synthesis of esters and amides. The

acid chloride may be obtained by treating the carboxylic acid with thionyl chloride, SOCl2.

Equally acceptable methods for the generation of the acid halide is by use of oxalyl chloride or
phosphorus tribromide (to prepare the acid bromide). There are several advantages to using an
acid halide to form esters, even though it adds a step (synthesis and purification) to the overall
reaction scheme. The acid chloride route frequently produces much higher yields, and no
excess of alcohol is required. The reaction can be carried out at room temperature and the
by-product of the reaction is HCl, which can easily be removed. There is one small hitch in the
reaction of acid halides with amines. The HCl formed reacts with the amine to form a relatively
inert ammonium salt. For an acid halide to be used to synthesize an amide, either an excess of
amine (at least 1 molar equivalent) or a proton scavenger is needed to neutralize the HCl. In
these cases, it is common to use a tertiary amine or pyridine. Neither will react with the acid
chloride, but each will easily form a salt with HCl.

Today’s lab consists of two parts:

I. You will synthesize an ester, methyl benzoate, from benzoic acid and
methanol.
 II. You will also observe the ease of reaction of acid chlorides by reacting
benzoyl chloride with water and ammonium hydroxide.

Green Chemistry

Let’s examine this experiment in terms of the fifth principle of green chemistry. This principle
calls for the use of safer (or minimal) solvents. The Fischer esterification of benzoic acid is
performed with methanol as both the solvent and the reagent. Since equilibrium processes such
as the Fischer esterification often require an excess of one reagent, using the reagent as the
solvent renders the need for a separate solvent unnecessary. The product isolation still requires
a biphasic workup which uses ethyl acetate, so it is not a perfect method. But, it is a step in the
right direction. We will build on this principle in later experiments.

Experimental Procedure

SAFETY!

Sulfuric acid is both toxic and corrosive. it will produce serious burns if it comes in contact with
your skin. Wear disposable nitrile gloves during the experiment. Wipe up any spills with a paper
towel, then wash the area with copious quantities of water. Finally, treat the area with aqueous
sodium bicarbonate to neutralize any remaining acid. Benzoic acid is an irritant (it’s also 5% of
cranberries by weight). Benzoyl chloride is a lachrymator. All transfers of this chemical should
take place in the hood. Rinse glassware contaminated with this chemical in the hood! Ammonia
is a corrosive and toxic. its vapors are highly irritating and present a respiratory risk to
asthmatics. Handle the ammonia under the hood. Wipe up any spills with a paper towel
(dispose of this immediately in the container provided for solid paper waste in the hood), wash
the area with copious quantities of water, and treat the area with aqueous sodium bicarbonate.

Part A
Synthesis of Methyl Benzoate

Begin heating 200 mL of water in a 250 mL beaker to near boiling on the heater-stirrer, heating
set to 4, set at the very back in the mini-hood. Dissolve 3.0 g (0.025 mol) of benzoic acid in 7
mL (5.5 g, 0.17 mol) of methanol in a 25 mL round-bottom flask. Carefully pour 3 mL of
concentrated sulfuric acid down the inner walls of the flask. Add a stir bar and equip the
round-bottom flask with an air condenser. Lightly grease all ground glass joints before
assembling the glassware and use a Keck clamp to hold the flask to the column. Clamp the
setup to the flexible frame support and lower the flask into the hot water. Heat the mixture under
reflux (methanol boils at 65 °C) for approximately 20 minutes. Do not allow the methanol to
distill out of the air condenser. You can start Part B while the reaction is under reflux.

After refluxing for 20 minutes, cool the reaction mixture and pour it into a 150 mL beaker
containing about 10 mL of saturated salt solution combined with approximately 20 g of ice.
Rinse the round-bottom flask with 12 mL of ethyl acetate and add this to the beaker. Mix the
phases thoroughly to extract the methyl benzoate into the ethyl acetate layer. Pour the biphasic
mixture into a large test tube. Use another 2 to 3 mL of ethyl acetate to rinse the beaker and
add this to the test tube. After the phases separate, aqueous layer with a Pasteur pipet. Do not
remove any of the organic layer. Is the organic layer on top or bottom? Wash the organic layer
first with 8 mL of water, then with two 8 mL portions of 10% sodium carbonate solution, finally
with 8 mL of saturated sodium chloride solution. Until the final washing, there is no harm in
allowing a little of the aqueous phase to remain in the test tube so as not to lose any of the
product.

Caution! When washing with the sodium carbonate, the mixture may bubble
vigorously. Add the sodium carbonate solution to your reaction mixture slowly, and
perform this wash in your hood. Have a clean beaker ready in case the foaming
 gets out of hand and overflows the tube. If the tube looks like it is going to bubble
over, simply put it in the beaker and wait.

Cleanly separate the aqueous phase from the organic phase after the final washing. Transfer
the ethyl acetate solution to a flask and dry with approximately 0.5 g of anhydrous magnesium
sulfate. Swirl the flask and determine if more drying agent is needed (if some of the magnesium
sulfate swirls, you have added enough; if it all clumps together, you will need to add a little more
to the vial). Obtain the mass of a 50 mL beaker. Decant the solution to the beaker and boil off
the ethyl acetate (set the temperature to 150 °C). Obtain the mass of the beaker and product.
Obtain an IR spectrum of the crude product.

Decant the dry ethyl acetate solution into a 25 mL round-bottom flask, and add a few boiling
chips. Don’t worry if a little magnesium sulfate slips into the distillation flask; it may serve as
additional boiling chips. Set up an apparatus for microscale simple distillation. Lightly grease all
ground glass joints and use a Keck clamp to hold flask to column. Distill the ethyl acetate using
the heating mantle at a low Variac setting (about 40%). The ethyl acetate has a boiling point of
77 °C, so any distillate that collects at or below this temperature is just solvent and may be
disposed of. Periodically remove the ethyl acetate from the collection well of the distillation head
with a Pasteur pipet. Dispose of the ethyl acetate in the appropriate waste bottle in the hood.
After most of the solvent has distilled and only 3 to 4 mL remains in the round-bottom flask, the
temperature will begin to fall. Then turn up the Variac setting to 70 to distill the methyl benzoate.
With a Pasteur pipet, periodically transfer the material that distills while the temperature is rising
into a separate container. This fraction will not be as pure as the fraction of methyl benzoate
that distills at a higher temperature; for the sake of purity, it is best to separate them. When the
temperature levels off near 195 °C, transfer the methyl benzoate (Caution! Hot liquid!) from the
collection well of the distillation head into a preweighed, capped vial. Collect the fractions that
collect once the temperature on the thermometer has plateaued. Weigh your product and
determine the yield. Obtain an IR spectrum of the purified methyl benzoate.
Part B

Hydrolysis of Benzoyl Chloride

Add five drops of benzoyl chloride to 5 mL of water in a 25-mL Erlenmeyer flask and then swirl
the flask. Heat the mixture on the hot-plate stirrer with occasional shaking. After the mixture
clears, cool the solution and collect the benzoic acid by filtration. Take the melting point of your
sample. (lit. mp 122–123 °C).

Ammonolysis of Benzoyl Chloride

Add 1 mL of benzoyl chloride dropwise to 5 mL of cold, concentrated ammonium hydroxide in a

large test tube under your mini-hood. Stir the mixture for two to three minutes. Carefully pour
the mixture into 10 mL of water. Break up any clumps of precipitate that may have formed and
collect the benzamide by filtration. After drying, determine the yield and melting point of your
product (lit. mp 128–129 °C).

Cleanup Procedures

Rinse all glassware that was used with benzoyl chloride with acetone in the hood. Dispose of
this rinse in the bottle provided in the hood. Dispose of your products and contaminated filter
paper in the individual containers labeled for this purpose in the hood. The aqueous phases
may safely be disposed of in the sink.

Experiment 10: The Aldol Condensation

Purpose:
 ● To use aldol condensation reactions to synthesize a colored
cyclopenta-dienone.
● To use UV-Vis spectrophotometry to characterize the dienone.
● To use computer visualization to better understand its unusual
three-dimensional structure.

Introduction

Aldehyde and ketones undergo an almost limitless number of reactions. The vast majority of
these fall under four general reaction types: nucleophilic addition to the carbonyl carbon,
substitution at the α-hydrogen, condensation reactions (reaction with another aldehyde or
ketone), and oxidation. In condensation reactions, the α-carbon of one carbonyl compound
becomes bonded to the carbonyl carbon of the other compound. This produces a
β-hydroxycarbonyl compound. Another name for a β-hydroxycarbonyl compound is “aldol.”
Because two molecules combine or “condense” to form one, this general type of reaction is
collectively known as the “aldol condensation.” Although the reaction in this experiment is base
catalyzed, aldol reactions can be run under either strongly acidic or strongly basic conditions.

In the first step of the base-catalyzed mechanism, a hydroxide ion abstracts one of the
α-hydrogens of acetaldehyde to produce the enolate. The carbanion of the enolate then reacts
with the carbonyl of another acetaldehyde molecule. The resultant anion reacts with water to
regenerate a hydroxide ion. This yields an aldol, 3-hydroxybutanal. This usually dehydrates to
yield the more thermally stable α,β-unsaturated aldehyde, 2-butenal (crotonaldehyde).
 zoom image

Figure 1.

Aldol condensations between different carbonyl compounds are known as mixed aldol
condensations. Mixed aldol condensations between two carbonyl compounds of similar
reactivity are not usually synthetically useful because they produce complex mixtures of
products. Typically, these reactions produce four major products in roughly equal amounts.
Many of the products formed in these reactions are capable of undergoing further aldol
condensation and readily oblige. This not only leads to a frightening number of products, but
also reduces the yield of the desired product (or products) and makes isolation difficult, if not
impossible. However, if the carbonyl compounds have very different reactivity or if one of the
compounds has no α-hydrogen, mixed aldol condensations can produce a single product in
high yields.

The Preparation of Tetraphenylcyclopentadienone

In this experiment, benzil and dibenzyl ketone (1,3-diphenyl-2-propanone, 1,3-diphenylacetone)

will be condensed under strongly basic conditions to form tetraphenylcyclopentadienone. This
reaction proceeds through two consecutive aldol condensations with dehydration to give a deep
purple, unsaturated, cyclic ketone. Dibenzyl ketone first loses an α-hydrogen to form the
enolate. The enolate than condenses with a carbonyl carbon of benzil. (Benzil has no
α-hydrogens and cannot form the enolate.) After protonation and loss of water, an enolate is
formed at the other a-carbon. The enolate carbon then attacks the other carbonyl group in the
same molecule in an intramolecular nucleophilic addition. Protonation and loss of water from
this intermediate leads to the formation of tetraphenylcyclopentadienone (TPCP).

Note: This reaction could also be run under acidic conditions to yield the same
product.

zoom image

Figure 2.

Carbonyl condensation reactions are widely encountered in nature. Fats, steroids, amino acids,
and many hormones have a carbonyl condensation as a key step in their biosynthesis.

Color and Absorption of Visible Light

The TPCP product produced in the reaction in this experiment is highly colored. Color arises
because the highly conjugated structure of the molecule allows for absorption of
electromagnetic radiation in the visible region (400 to 700 nm wavelength). The absorption
results in an electron from a bonding or antibonding orbital in the structure being transferred to
a higher-energy nonbonding orbital. The energy gap between the orbitals determines the
energy (and thus the wavelength) of electromagnetic energy that is absorbed. In organic
molecules, absorption of energy in the UV or visible region is most often the result of the
transition of pi electrons in a conjugated r system being promoted to nonbonding pi asterisk
times orbitals. The longer the conjugated system, the longer the wavelength of light that is
absorbed.

Light observable by the human eye lies in the region of 400 to 700 nm. White light consists of
light over the entire region. Light of particular wavelengths within this region would appear
colored (see Table 1). If light in one region is selectively absorbed, the resulting light that is
transmitted (or reflected) will be observed as colored. It is important to recognize that if light of a
particular wavelength (color) is absorbed, the resulting color transmitted through the solution will
be the complementary color. Thus, a solution that absorbs violet light will appear yellow. It is
also important to recognize that molecules absorb electromagnetic radiation over a range of
wavelengths, not a single wavelength. Thus the observed color is a function of the relative
absorption of various colors by the molecules. Note that most objects are absorbing over a
band of wavelengths.

Wavelength,
Color of Light
Absorbed
straight lambda Resulting Color*

(nm)

400 Violet Yellow

430 Blue Orange

500 Green Red

580 Yellow Violet

600 Orange Blue

650 Red–Orange Blue–Green

700 Red Green

* This is the color transmitted through a solution with light of wavelength λ being absorbed.

Experimental Procedure

SAFETY!

WEAR nitrile gloves for this experiment. The potassium hydroxide pellets and the ethanolic
solution of potassium hydroxide are toxic corrosives. These pose a particular hazard to your
eyes (reported to include, in addition to cornea damage, instantaneous and debilitating pain).
Alkali on your skin produces a slick, soapy feeling. Wipe up any spills and wash the area with
copious quantities of water. Rinse the area with the aqueous boric acid solution. The hexanes
you are using are flammable. Hexanes are also volatile irritants, and all transfers of this material
should take place under the hood.

There are three components to today’s lab period:

Part A. Synthesis and Characterization of TPCP

Part B. Spectrometric Analysis of TPCP

Part C. Computer Visualization of the TPCP Structure

Since there are only two computers for the visualization portion of this experiment, some
students need to be on the computer early in the lab period—either before starting the synthesis
or while the reaction is being heated or cooled.

Part A. Synthesis and Characterization of TPCP

The Aldol Condensation

Dissolve four pellets of potassium hydroxide in 6 mL of absolute ethanol in a small plastic

beaker. Use a spatula to crush the pieces of potassium hydroxide to aid the solution process.
While the potassium hydroxide is dissolving, set up a 25 mL round-bottom flask with an air
condenser and a heating mantle. Lightly grease all ground glass joints before assembling the
glassware and use a Keck clamp. Obtain 10 mL of the prepared Aldol Condensation Solution
from the bottle in the chemical hood and put it into your 25 mL round-bottom flask. This 10 mL
solution contains 0.3 g (1.43 mmol) of benzil and 0.3 g (1.43 mmol) of dibenzyl ketone. Use the
heating mantle (use tile plates from your common drawer around the flask) to heat the
benzil/dibenzyl ketone solution to boiling (start with a setting of 35%), then reduce heating to
allow boiling to stop and, using a Pasteur pipet, slowly add the ethanolic solution of potassium
hydroxide at a dropwise rate. Caution! Foaming may occur. The mixture will immediately turn a
deep purple color. After adding the potassium hydroxide solution, allow the mixture to reflux for
about 15 minutes. Swirl the flask several times during this period.

Product Purification

Cool the mixture in an ice-water bath (below 5 °C). Collect the deep purple crystals by vacuum
filtration and wash them with three 1 mL portions of ice-cold 95% ethanol. The filtrate should be
purple-pink and not brown. Dry the crystals by drawing air through them for about five minutes.
Weigh the crystals and determine the percent yield. (If necessary, you may store the crystals
and determine their weight and melting point during the next laboratory period.) The yield of this
reaction is often too low to obtain a melting point of your product (lit. mp 217–220 °C), so this
characterization data is not required for this experiment.

Part B. Spectrometric Analysis of TPCP

Product Characterization

You will be using Beer’s law to determine the concentration of TPCP in the solution you
prepare. TPCP crystals are highly colored, having absorption peaks in both the UV and visible
light wavelengths. (See discussion of UV spectroscopy in on-line description of this
experiment.)

The absorbance, A, of the sample at a particular wavelength is governed by Beer’s law, A = ε I

c

Where:

c = sample concentration in moles per liter (or mmol/mL)

l = path length of light through the cell (cuvette) in centimeters

ε = the molar extinction coefficient (or molar absorptivity) of the sample

Time management is critical. Read the following procedure carefully before beginning. Delay
in any of the steps can force you to repeat this entire procedure.

Obtain a 5 mL volumetric flask and stopper. Transfer a small amount of your dried TPCP
crystals (equal to the size of a match head) into the 5 mL volumetric flask. (It is very important
that your sample be completely dry.) Add hexanes (use the Pasteur pipet provided on the
hexanes bottle) to the mark on the volumetric. Do the transfer of hexanes in the hood. Stopper
the volumetric flask and shake it vigorously for 30 seconds. Not all of these crystals will
dissolve—this is exactly what you should expect.

Go immediately to your workstation and within one minute (30 or more seconds), quickly place
about one mL of your TPCP/hexanes solution in a cuvette (use a 9” glass pipet for this transfer).
Wipe the outside of the cuvette with a Kimwipe, if necessary. Take your prepared cuvette to the
UV-Vis spectrometer and place it in the sample holder. The spectrum should appear on the
screen. Print the spectra immediately (press Control P, then Enter).

TPCP has three absorption maxima (peaks) in the UV spectrum that you are obtaining. You will
only use the region at ~330 nm to determine if the spectrum you obtain is acceptable for your

needs. Use 2950 for epsilon330 in your calculations. note that this is not the absorption

responsible for the color of TPCP.

If the absorption at ~330 nm is between ~0.9 and ~1.5, you are finished. If the absorption is less
than ~0.9, put the cuvette sample back into the 5 mL volumetric flask and shake it for an
additional 10 seconds. Repeat as above to obtain spectrum. If the absorption is greater than
1.5, you will need to start over (with a new sample).

TPCP is not very soluble in hexanes, but it will continue to dissolve over time in the hexanes,
giving a more concentrated solution. This solution will absorb more UV light. Within a short time,
the solution will become so concentrated that it will absorb all of the light between 300 and 360
nanometers (nm) (and the absorbance value will exceed a value of 2). Beer’s law is not valid
under these conditions.

Important! Do not have any chemicals near the laptops (the cuvette may be in the area).

After you have obtained your spectrum, remove your cuvette from the sample holder in the
UV-Vis spectrophotometer. When you are finished, pour the solutions in the cuvette and that
remaining in the 5 mL volumetric flask into the waste bottle labeled specifically for this purpose
in the hood.

Important: Rinse the 5 mL volumetric and stopper twice with hexanes using the
squeeze bottle of hexanes provided for this purpose in the hood.
Return the stopper and volumetric flask to your bin. Place the used cuvette in the beaker
provided for this purpose in the hood.

Hexanes is a generic term used to describe a fraction of aliphatic compounds that boils at 69

°C. the majority of these have the formula of C6H14. this fraction can include a variety of

compounds including methylpentanes and cycloalkanes, which are very difficult to separate by
distillation. Hexanes can be used in place of pure n-hexane (which is more expensive) for most
applications. the hexanes used for this experiment are UV grade. UV grade means that the
solvent being used is UV transparent (does not absorb) in a specified region.

Part C. Computer Visualization of the TPCP Structure

Sometime during the lab period, go to one of the portable computers at the TA desk. On these
computers you will find a 3D representation of TPCP—the product of your aldol reaction
experiment. This structure has been geometry-optimized to provide the structure of lowest total
energy by Spartan calculations. Examine this structure following the instructions below to
generate answers to the questions on the worksheet.

Notice! You are to complete this computer visualization of TPCP individually.

Purpose

The purpose of this exercise is to use the graphical abilities of the computer to give you another
mechanism for visualizing the three dimensional properties of molecules. I strongly suspect that
your concept of the TPCP structure prior to this exercise was significantly different than what
you will see here.
 zoom image

Figure 3.

The above structure implies that all carbon atoms are in the same plane—this planar structure
would give a system in which the conjugation of the phenyl rings with the pi system of the
cyclopentadienone ring would be maximized, since all p-orbitals are oriented in the same
direction.

Part C of the In-Lab Observations sheet indicates what information you need to record while
looking at this structure. Every student should complete this exercise individually.

Important! Follow these instructions exactly! Every bullet contains an instruction!

Visualization Instructions

The computer should already be running Spartan and contain a structure of TPCP on the
screen. If not, select File | Open | and select the “TPCP.spartan” file.

I. Visualization in Space-Filling Rendering

● Prepare to rotate the molecule by clicking on View button if it is not the active
button. This is the first button to the right of the Save button. Move the cursor
into the drawing area. The cursor is now an arrow point.
 ● Hold the mouse button down and move the cursor to rotate the molecule. Try
several orientations so that you look at the molecule both in the plane of the
five-membered ring and perpendicular to the five-membered ring.
● To see the molecule with atoms of a relative size approximating real atoms,
use the mouse to select from the menu bar | Model | Space Filling |.
● Write your explanation on the worksheet for the phenyl groups not being
oriented so that the phenyl rings are coplanar with the five-membered ring,
as implied by the structure in Figure 3.

II. Visualization in Tube Structure

● Now choose | Model | Tube | to go back to the original display.

● Again, hold the mouse button down and move the cursor to rotate the
molecule so that the five-membered ring is perpendicular to the plane of the
computer screen (rotate the molecule 90° by holding down the mouse button
and moving the cursor straight down). Note which way the phenyl rings are
rotated from planarity with the ring—clockwise or counterclockwise as you
look past a phenyl in front to the five-membered ring behind it. (Choose the
direction that requires the least amount of rotation.) If you flip the molecule
over like a pancake is flipped (rotate the molecule 180° by holding down the
mouse button and moving the cursor straight down or up), are the rings tilted
in the same direction or a different direction? Record answer on worksheet.
● Now rotate the molecule so that the five-membered ring is in the plane of the
screen. Visualize running a stick skewer through the center of the
five-membered ring. If the skewer is then rotated clockwise and you consider
the phenyl groups as solid blades, would the system pull air toward the hand
 rotating the skewer, or blow air away from the hand holding the skewer?
Record answer on worksheet.
● This molecular structure is chiral in the same way that a screw or a propeller
is chiral. Describe how the mirror image of this structure would differ from the
representation shown. Record answer on worksheet.

III. Dihedral Angle Measurements

You can see that the extent of rotation away from planarity is not the same for all phenyl groups;
the distortion is less for the two phenyl groups adjacent to the oxygen containing only an
oxygen substituent. We can measure the angle of deviation from planarity in the following way.

● Rotate the molecule until the five-membered ring is in, or nearly in, the plane
of the computer screen. Make sure you know which carbons of the phenyl
groups are above the plane of the screen, then click on the Dihedral button.
● Let’s first measure the rotation from planarity for a phenyl adjacent to the
carbonyl. Click sequentially on the carbonyl carbon, C2 in the
cyclopentadienone, the phenyl carbon attached to C2, and finally the phenyl
carbon closest to the carbonyl.
● You should now have four adjacent carbons highlighted with green balls, and
the lower right of the screen should have a box containing a bond angle
following the words “Dihedral (Cw,Cx,Cy,Cz).” If this torsion angle is more
than 90°, you selected the wrong second phenyl carbon. Start over and
make sure the fourth carbon is the one oriented closest to the carbonyl
group.
● Record the torsion angle shown (less than 90°) in Section III of the
worksheet.
 ● We will now measure the extent of rotation for a phenyl group farther from
the carbonyl group. Click sequentially on the C2 carbon, the C3 carbon, the
phenyl carbon attached to C3, and then the next adjacent phenyl carbon that
is closer to C2. If this torsion angle is more than 90°, you selected the wrong
second phenyl carbon.
● Record this torsion angle (it must be less than 90°) in the worksheet.
● Close the file by selecting | File | Close |. (Select No when asked “Save
changes to TPCP?”)

Cleanup Procedures

Rinse all glassware with acetone. Catch this first rinse and dispose of it in the container
provided in the hood. Dispose of all contaminated filter paper in the appropriate container in the
hood. Dispose of the TPCP in the special container labeled for this purpose.

Experiment 11: Organic Dyes—Indigo and

Azo Dyes

Purpose:

● To synthesize two different organic dyes and use these dyes to observe their
effectiveness in dyeing both synthetic and natural fabrics.

Introduction
Despite the current fad that “organic” is natural, organic was originally described as the
chemicals derived from living things. The alchemists recognized that organic chemicals were
somewhat different from other materials in nature and their explanation was that in addition to
the basic elements of earth, wind, fire, and water, organic chemicals also contained the “breath
of life.” That definition has evolved over time to include covalent compounds that contain carbon
and usually hydrogen along with other elements. These chemicals were not limited to those
produced by living things.

When you think of ancient alchemists, you always think of ancient efforts to change lead into
gold. In truth, far more effort was spent trying to create color. The ancient fibers cotton, wool,
mohair, flax, and silk make quite durable but remarkably drab and somewhat dingy fabrics and
textiles. Mineral-derived colors, while providing pigments useful as paints and pottery glazes,
just didn’t work with organic fibers. Colors derived from roots, berries, leaves, and flowers were
tried. They provided a limited number of colors, usually in the browns, greens, and yellows to
drab reds. Tyrian or imperial purple was derived from sea snails, Hexaplex trunculus. Indigo
was originally isolated from an Indian plant, Indigofera tinctoria, and more recently from the
woad plant, Isatis tinctoria, of Europe. Even the bright red of the British “Red Coats” came from
a scale insect that feeds primarily on prickly pear cactus in tropical and subtropical South
America and Mexico. The vibrant colors that we take for granted in the fabrics of today were
prohibitively expensive until the late 19th century. This is when chemists discovered methods of
synthesizing brightly colored organic compounds that worked very well as fabric dyes.

Discussion

Today’s lab consists of three parts. You will synthesize two different organic dyes, and then as
the third part you will use each of these chemicals to dye several types of natural and synthetic
fabrics. To be a dye, a chemical must be able to absorb one wavelength of light (e.g., green)
causing its contrasting wavelength of light (e.g., red) to be reflected. This is caused by the
presence of “conjugated pi bonds” (i.e., many –C=C–, –C=N–, or –N=N– adjacent to each
other). The natural orange color of carrots is caused by eleven such –C=C– bonds. In the past,
natural dyes were isolated from snails, plants, or insects by a series of tedious and sometimes
complicated series of steps. As a result, these dyes were not readily available and expensive.
They also tended to be very sensitive to both light and laundering—leading to rapid fading or
deterioration of the original color. Roughly 150 years ago, in a failed effort to synthesize quinine
(a natural material useful in the treatment of malaria), the dye Aniline Purple (mauve) was
discovered. Shortly after that, Baeyer (Americanized as Bayer) developed a synthesis of indigo,
which had previously been isolated from plants. Because these dyes could be produced from
relatively inexpensive sources, including coal tar, synthetic dyes are generally called “coal tar
dyes.” Indigo, whether natural or synthetic in origin, is also generally listed as a coal tar dye.

The third part of the experiment will come from your observations of the interaction of your dyes
with a fabric. For a fabric dye to work, it has to interact with the fabric so that it is not
immediately removed upon laundering the fabric. On a molecular level this can involve ionic
interaction, hydrogen bonding, covalent bonding, or simply solubility. The affinity of a dye for a
particular fabric depends upon the chemical structure of the dye and of the fabric molecules and
the interaction between them. This interaction and the relative solubility of the dye are both
related to its fastness or ability to maintain its color without fading or washing away.

You will be dyeing a strip of fabric that contains samples of eight (8) different types of fabrics.
(See end of Experimental Procedure for key to fabric strips.) Whether natural or synthetic, all of
these fabrics are high molecular weight polymers. Each is a long chain molecule made up of
smaller repeating units. The structure of each of these repeating units is shown in Figure 1. The
number of repeating units (n) varies depending upon the fiber and how it is prepared. A
discussion of the chemical composition of each of the different fabric types on your test strip
follows.

Cotton is a fibrous form of a polysaccharide made up of glucose units attached to one another
by covalent bonds. This polysaccharide is also known as cellulose and often found in
nonfibrous form. There are three polar hydroxyl groups (–OH) on each of the glucose subunits
in cellulose. Several fibers are made by chemical modification of cellulose derived from a
variety of sources. Cellulose diacetate, known as diacetate, and filament acetate are both
chemically derived from cellulose. Diacetate averages two acetates (esters) and one free
(unreacted) –OH group per glucose subunit. Filament acetate, also known as triacetate, has at
least 92% (if not all) of the hydroxyl groups (– OH) in cellulose converted to the acetate esters.
The presence of acetate side chains do make the acetates softer than cotton. However, each
acetate removes one highly polar –OH group and reduces the number of strong binding sites
for dyes. Viscose (Rayon) is manufactured by chemical modification of non-fibrous cellulose
and regenerating the cellulose as a fiber. Because it is produced from naturally occurring
polymers, it is neither truly natural nor truly synthetic. Rayon is sometimes referred to as a
semisynthetic fiber. Rayon is also sometimes known as art silk and Viscose Rayon. Bleached
cotton is softer and more hygienic than raw cotton.

zoom image

Figure 1.

Polyacrylics like Creslan and Orlon are polymeric acrylonitriles manufactured by different
companies. The polyacrylics contain one –CN per repeating unit. While chemically identical,
they differ slightly in their molecular weight and fiber characteristics based upon manufacturing
differences.

Wool, silk, and Nylon are polyamides. Wool and silk are naturally occurring polymers made up
of amino acid repeating units. Many amino acids have acidic or basic side chains that are often
charged. Worsted wool is high-quality, long-shaped wool used for tailored garements as
opposed to woolen wool which is used for knitted items. Nylon® is a polymer made with a
diamine and a dicarboxylic acid, resulting in a polymeric amide of repeating units from the
amine and carboxylic acid. The numbers associated with Nylon (e.g., Nylon 66 and Nylon 56)
refer to the total carbon chain length of the amine followed by the carbon chain length of the
dicarboxylic acid. The highly polar amide groups of the polyamides (natural and synthetic) do
provide sites for hydrogen bonding to dye molecules. All polyamides are fire resistant and tend
to quit burning once the source of the flame is removed. Dacron 54 and Dacron 64 are
polyesters, technically polyethylene terephthalate, commonly abbreviated as PET or PETE.
Dacron 54 is untreated PETE, while Dacron 64 has a brightener added. Polyesters have only
weakly polar groups and do not bind highly polar dyes. They require hydrophobic dyes that can
be “dispersed” within the fibers.

Indigo

Indigo is a natural dye originally isolated from the plant, Indigofera tinctoria, that has been used
in India for roughly 4000 years. In Northern Europe, the woad plant, Isatis tinctoria, which also
contains indigo, was used as a source of this blue dye. The woad plant contains other
chemicals, so the blue dye derived from this source was not a “pure” blue like the indigo from
India. In 1879, Baeyer developed a synthesis of indigo. Today, virtually all of the indigo used is
synthesized rather than isolated from the plant. Indigo will be synthesized by treating
2-nitrobenzaldehyde and acetone with sodium hydroxide. A series of condensations,
disproportionations, and oxidations take place within a few seconds to produce indigo.

zoom image
 Figure 2.

Indigo is a vat dye that is highly insoluble. For indigo to be used as a fabric dye, it must first be
reduced to form a water-soluble derivative, leucoindigo. Although leucoindigo is technically
colorless, the container of leucoindigo will appear pale yellow. The fabric is soaked in a solution
of leucindigo and then allowed to air dry. The exposure to air oxidizes leucoindigo back to
insoluble indigo, which is trapped in the fabric.

Natural indigo was isolated by first soaking the plant leaves in water and allowing them to
ferment until the water became deep blue. the dye was precipitated by the addition of a strong
base such as lye. The dried cake was compressed and shipped to the dyeing location. The
indigo was then placed into a large container, vat, treated with a reducing agent, and allowed to
react (ferment) until it was reduced to the soluble and colorless leucoindigo. Traditionally, this
involved treating the powder with urine. today, reducing agents such as sodium dithionite are
used in the place of urine. The fabric is dipped into the colorless solution and then allowed to
dry. Exposure to air causes the leucoindigo to oxidize back to the highly colored and insoluble
indigo. This is the process used to color blue jeans. The color wears off rather than washes out.
As of 2012, over 50,000 tons of synthetic indigo are produced annually with over 40,000 tons
being used specifically to produce denim for blue jeans.

Azo Dyes

Azo dyes are synthetic colors that contain an azo group, –N=N–, as part of their structure. Azo
groups do not occur naturally, and most azo dyes contain only one azo group. Azo dyes
account for roughly 60–70% of all dyes used in the food, textile, and leather industry. In theory,
azo dyes can be made in all of the colors of the rainbow by changing the structure of the groups
bonded to the azo group. In reality, the red/yellow dyes are more common than the blue/brown
dyes.
 zoom image

Figure 3.

Azo dyes are made as part of a two-step reaction. First an aromatic primary amine, ArNH2, is

converted into a diazonium salt and then a reactive aromatic ring, frequently a phenol, is added.
The reaction is an electrophilic aromatic substitution reaction with the aryl azide as the
electrophile. Since the structure of both the starting aromatic amine and the reactive coupling
reagent can be modified extensively, an almost limitless number of dyes are possible. The
reaction is quite simple and generally run at temperatures at or below room temperature. The
dyes are stable and do not fade when exposed to air or light. The dyes are remarkably nontoxic
and are technically too small to elicit allergic response. However, some of the aromatic amines
used to prepare azo dyes are considered carcinogenic, and there are mechanisms for azo dyes
to be broken down biologically to these component amines, so such dyes are prohibited as food
colorants.

In this experiment, each pair of students will prepare one of several different azo dyes by using
different aromatic amines and phenolic compounds in the synthesis. Each pair of students will
be assigned a particular pair of reagents. The code for the assignments are shown in the
following graph. Your TA will give you your assignment code.
 zoom image

Figure 4.

Experimental Procedure

SAFETY!

You will need to WEAR gloves during this experiment. Aromatic nitrogen compounds can be irritants and
mutagenic. Avoid contact with skin. Sodium hydroxide is a caustic agent. Phenolic compounds are skin
irritants. indigo can be absorbed by the skin and all of the dyes will stain skin and clothes.

Part A. Indigo

(1) Synthesis of Indigo

Place ~0.1 g (100 mg) of 2-nitrobenzaldehyde into a test tube and, using a 10 mL graduated cylinder, add
2 mL of reagent acetone to the test tube. Swirl the tube to dissolve the solid 2-nitrobenzaldehyde, and
then add 25 drops of distilled water and swirl gently. Now slowly add 15 drops of 3.0 M NaOH solution.
Your solution should rapidly darken, and a deep purple solid (indigo) should precipitate from the solution.
Place the test tube in a rack to stand while you complete the synthesis of your azo dye. (Part B)

When you return from Part B, filter the solution with a Büchner funnel/125 mL filter flask and wash the
solid with distilled water until no more color washes from the solid. Finish by washing the solid with 95%
ethanol. Assess the mass of the solid.

(2) Reduction to Leucoindigo

Take the 250 mL filter flask from your bin that has a pipet bulb with a slit cut in it attached to the sidearm.
You will also need the cork that fits the flask. The slit in the pipet bulb will allow you to safely heat the
stoppered flask without the danger of pressurizing the flask. This normally closed “opening” will also limit
the amount of oxygen allowed into the flask.

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Figure 5.

Place the solid indigo from the filter paper into this 250 mL filter flask, then add 10 mL of 3 M NaOH to the
flask, stopper it with the cork, and begin heating the flask (keep the pipet bulb on the side arm) on the
heater-stirrer with an initial setting of 6 (DO NOT BOIL). Swirl occasionally to mix. While the suspension
is heating, prepare some chemicals you will need for the next few steps of the experiment. First, prepare a
10% solution of sodium dithionite by dissolving 3 g of sodium dithionite in 27 mL of water in the 150-mL
beaker. Then obtain 75 mL of distilled water in the 100 mL graduated cylinder.
When the indigo suspension is hot, add 2 mL of 10% sodium dithionite (Na2S2O4) solution. Return the

cork to the flask and continue heating and swirl the suspension. Continue to add 10% Na2S2O4 solution in

2 mL increments until the indigo has dissolved, leaving a clear yellow solution.

Note: You may not need to add all of the sodium dithionite solution. Stop the addition once
all of the indigo has dissolved.

(3) Dying a Fiber Strip and Air Oxidation

When you obtain the clear yellow solution, add the 75 mL of distilled water to your flask and add one of
your fiber test strips. Use a spatula to make sure the strip is immersed in the solution. Do not be
concerned if a blue precipitate forms on the surface of the solution when you make this addition. Replace
the cork and heat the mixture again. Heat the flask for at least 10 minutes before removing it from the heat
and allowing it to cool. Once the solution has cooled, carefully remove the cloth strip with forceps (there
are some in your equipment drawers), use paper towels to avoid dripping dye solution onto the desktop,
and lay the fabric strip on some dry paper towels. Pat with a paper towel to remove most liquid. Allow it to
dry somewhat and then take the fabric to the sink in a 250 mL GLASS beaker and rinse the fabric strip
with water to remove any clumps of dye and then dry again.

Record how well each type of fabric is dyed by indigo in the Table on the In-lab Observations page.

Part B. Azo Dye

First—Record the Dye Combination (A1–C4) assigned to your group by your TA. Then write the names
and structures of the two starting materials you will be using. You will need to calculate the weight
corresponding to 2.6 mmol of your assigned phenolic compound (this weight will NOT be the same for all
four possibilities). Weigh out both of these materials before starting the experiment. Also prepare an
ice-water bath in a 250 mL plastic beaker and a hot-water bath by heating 100 mL of water in the 250 mL
glass beaker on the heater-stirrer. (Make sure indigo has been well rinsed from beaker used in Part A.)
(1) Diazonium Salt Preparation

In a test tube place 0.49 g (2.8 mmol) of your assigned aminobenzenesulfonic acid, and add 5 mL of
0.245 M sodium carbonate. A clear, but colored, solution is obtained by warming the test tube in the
hot-water bath. Remove the test tube from the water bath and, using the preset micropipettor, add 0.50
mL of a 3.0 M solution of sodium nitrite in the hood. Remember, do NOT eject the tip from these
micropipettors. The partner should add 3 g of ice to a second test tube and slowly add 0.53 mL of
concentrated HCl using the preset micropipettor set up with the HCl solution. Then the solution from the
first test tube is added dropwise with a Pasteur pipet to the second test tube. The resulting mixture is
swirled to mix well and then placed in your ice-water bath (prepared in a 250 mL beaker) to induce
precipitation of the diazonium salts. The suspension is used in the next step.

(2) Coupling Reaction

In a 25 mL Erlenmeyer flask with a stir bar, place 2.6 mmol of phenolic coupling reagent (1- or 2-naphthol,
salicylic acid, or 4-chloro-3-methylphenol depending on your assigned dye combination) and add 2 mL of
a 3 M aqueous solution of sodium hydroxide. Clamp the Erlenmeyer flask in the prepared ice-water bath.
Then add the suspension of diazonium salts prepared in the first step (mixture of solid and liquid with the
Pasteur pipet) portion-wise with a Pasteur pipet to the Erlenmeyer flask. The reaction mixture should be
stirred with a stir bar after each addition. The color of the solution should change during this period of
reaction. Let the reaction proceed for about 10 min with stirring. Then heat the suspension on the
heater-stirrer while stirring until the solid dissolves. Carefully add 1 g of NaCl and continue heating and
stirring to dissolve the sodium chloride.

Remove the Erlenmeyer flask from the heat and allow it to cool to room temperature first. Then cool the
flask in an ice-water bath. After it has cooled, use a Büchner funnel and 250 mL filter flask to collect the
solid by vacuum filtration. Wash the solid with 2 mL of saturated NaCl solution and dry it by pulling air
through the funnel. Remove the filter paper and allow the product to air dry. When it is dry, transfer the
product to a weighed watch glass to determine the yield of your azo dye. If you do not obtain much
precipitate, save the filtrate and use this solution to dye the fabric strip. Note: If you proceed with this
route, you will need to be extra diligent when washing the fabric strip to ensure that you have thoroughly
removed all chemical residues.
(3) Dying a Fiber Strip

Dissolve 50 mg of the azo dye prepared in the previous step in 20 mL of water in a 150 mL beaker. Put a
strip of the multi-fiber cloth (see key to multi-fiber cloth below) in the solution of the azo dye (or your filtrate
if you did not obtain any precipitate of your azo dye) and keep it immersed (use beaker tongs) while
heating the solution vigorously on the heater-stirrer for about 10 minutes. Remove the beaker from the
heat. At the sink, remove the cloth strip with a pair of large forceps and, after it has cooled slightly, rinse
the fabric with tap water. Pat dry the dyed fabric with a paper towel. Record the effect on the different
fabric strips in the table on the In-lab Observations page. Then compare the color effects of your dye with
those of at least one of the other azo dye combinations. Record the fiber identity and dye combination that
give the brightest/deepest colors.

Cleanup Procedures

Aqueous solutions of dyes should be poured into the liquid waste container. The solid dyes should be
placed in the solid waste container. Rinse glassware with acetone to ensure the removal of all traces of
dyes.

Return the pipet bulb with a slit attached to one of the 250 mL filter flasks with your glassware
bin—even if it is stained.

Rinse and return the cork to your bin as well—even if it is stained. Place used gloves in the
appropriate waste container.

Key to multi-fiber strip

Black Thread
1. Filament Acetate

2. Bleached Cotton

3. nylon 66 (spun polyamide)

4. Disperse Polyester

5. Polyacrylic

6. Silk
7. Viscose Rayon

8. Worsted Wool