The Nitration of Aniline.
Background: The nitration of aniline somewhat problematic. One solution to the
problem is to use an acetyl group (CH3CO) to “protect” the nitrogen atom from some
unwanted reactions. The acetyl group is useful for this purpose because of its electronic
effects, it is rather bulky, and it is easily removed by hydrolysis after the nitration
reaction is complete. We will perform a three-step reaction sequence in order to nitrate
aniline safely. This will introduce you to the use of protecting groups in organic
synthesis, and the principles of electrophilic aromatic substitution reactions. The
reactions involved in the three-step process are outlined below. Please note that we will
cover the theory of nucleophilic acyl subsitution (involved in step 1 and again in step 2)
later in the course. For this reason we will take the unusual approach of performing step
2 first. Later we will do steps 1 and 3. Your task will be to make good notebook entries
for step 2 now so that we can write this up as a single project. You will be provided with
some problems to turn in at the end of today's lab.
step 1: adding the protecting
group: O O
acetic anhydride acetanilide acetic acid
step 2: nitrating the
acetanilide O N
step 3: removing
the protecting group:
1. HCl / H2O
O N O N
Step 1: the preparation of acetanilide:
1. Aniline is toxic and can be absorbed through the skin. Use in a fume hood and
wear gloves. Better yet, let your lab partner handle the stuff.
2. Concentrated hydrochloric acid can cause severe burns.
3. Acetic anhydride is lachrymatory.
To 60 mL water in a 125 mL Erlenmeyer flask add 2.5 mL concentrated hydrochloric
acid with mixing. Add 2.5 mL aniline (density 1.02 g cm-3) and swirl the mixture.
If the solution is colored, add a small amount of decolorizing charcoal, swirl the flask for
about one minute, and filter off the carbon. In a separate container dissolve 4 g sodium
acetate in 10 mL water. Warm the anilinium chloride solution to 50oC on a water bath
and add 3 mL acetic anhydride (density 1.08 g cm-3). Swirl to effect dissolution and add
the aqueous sodium acetate quickly. Swirl the flask a couple of times and set it in an ice-
bath for 20 min. Vacuum filter the crystals of the amide formed and wash with a small
amount of ice-cold water.
Step 2: Nitration of Acetanilide FIRST WEEK OF THIS PROJECT
acetanilide O N
In a 125 mL Erlenmeyer flask, dissolve 3.4 g of acetanilide in 4 mL glacial acetic
acid. You may need to warm the solution gently in order to get all the solid
material to dissolve. Use a hot plate stirrer if necessary, and for heaven’s sake
stir the solution. DO NOT OVERHEAT. When all the material has dissolved, cool
the solution in an ice bath. Crystals may begin to form. Add 5 mL of concentrated
ICE COLD sulfuric acid. Add the sulfuric acid SLOWLY 1 mL at a time using a
medicine dropper or pipette. Leave this in your ice bath to cool to 5 °C.
Obtain 4.3 mL of a mixture of concentrated sulfuric acid and concentrated nitric
acid. (ONLY OPEN THE MIXED ACIDS IN THE HOOD!!) Remove the flask
containing your acetanilide-acetic acid-sulfuric acid mixture from the ice bath and
add the nitrating mixture DROPWISE using a disposable pipette. Swirl the flask
to mix the reagents thoroughly. Keep the temperature in the 20-25 °C range as
you add the nitrating mixture. If the temperature gets too hot, cool the flask in the
ice bath. Add 1-2 drops and swirl, monitoring the temperature carefully. After all
the nitrating mixture has been added, allow the solution to stand at room
temperature for 40 minutes in order for the reaction to go to completion. DO NOT
LEAVE IT FOR MORE THAN ONE HOUR or decomposition or a second nitration
may start to occur. Pour the reaction mixture slowly, with stirring, into a mixture
of 50 mL of water and 10 mL of ice. Collect the product by vacuum filtration
using your Buchner funnel. Press the solid firmly with your spatula to help
remove as much liquid as possible. Since there is still a lot of the nitric/sulfuric
acid mixture remaining, transfer the solid filter cake to a beaker containing 40 mL
of ice cold water. Mix the suspension thoroughly to help wash off the acid and do
another suction filtration using a new piece of filter paper in your Buchner funnel.
Disconnect the filter flask from the vacuum and add an additional 10 mL cold
water. Reconnect the vacuum and filter off this water. Recrystallize all but a
small spatula tip full of the solid from ethanol. Place your recrystallized solid in a
dry beaker and spread out the crystals. Label the beaker with the structure of the
product, your names, which lab day you have, and we will place it an oven to dry
overnight. It is your responsibility to weigh it the next day, and to transfer it to a
labeled product vial (structure, your name, mass) and then to place it in your
cabinet until next week. You are then to get a melting point on the solid and
determine whether you made 2-, 3-, or 4-nitroacetanilide.
Step 3: Hydrolysis of Nitrated Acetanilide
Transfer your weighed nitroacetanilide to a round bottomed flask along with 5 mL
70% sulfuric acid per gram of nitroacetanilide. Stir and reflux for 30 minutes. Pur
the reaction mixture into cold water (about 7 mL water per gram of
nitroacetanilide you began with). Add concentrated ammonium hydroxide
(HOOD) with stirring until basic. You should now have a precipitate. If not, add
more base. Vacuum filter. Wash the solid with water until the solid no longer
smells of ammonia. Place your solid in a dry beaker and spread out the crystals.
Label the beaker with the structure of the product, your names, which lab day
you have, and we will place it an oven to dry overnight. It is your responsibility to
weigh it the next day, and to transfer it to a labeled product vial (structure, your
name, mass) and then to place it in your cabinet until next week. You are then to
get a melting point on the solid and determine whether you made 2-, 3-, or 4-