Lab.
The general reaction :
1
preparation of acetanilide from aniline or acetylation of aniline
Acetylation.
Compounds of the type ROH (alcohols and phenols), and also compounds of the
type RNH2 and R2NH (primary and secondary amines) can be directly acetylated,
the reactive H atom being replaced by the acetyl radical, -COCH3.
Primary and secondary amines give acetyl derivatives of the type RNHCOCH 3 and
R2NCOCH3 respectively, which can be regarded as mono-and di-substituted
derivatives of acetamide, H2NCOCH3.
The chief method of acetylation of amines :
Heating with a mixture of acetic anhydride and acetic acid.
If a primary or secondary amine is heated with glacial acetic acid, the
corresponding acetyl derivative is produced, but the process is often extremely
slow. If, however, the acetic acid is mixed with acetic anhydride, rapid
acetylation usually results.
One disadvantage of using acetic anhydride is that with primary amines,
traces of the diacetyl compound, RN(COCH3)2, may be formed: the chances of
this secondary acetylation are, however, usually remote, and recrystallisation
from an aqueous solvent will generally hydrolyse the diacetyl derivative rapidly
back to the mono-acetyl compound
2
Acetanilide is an odourless solid chemical of leaf or flake-like appearance. It is
also known as N-phenylacetamide, acetanil, or acetanilide
Acetanilide was the first aniline derivative found to possess analgesic as
well as antipyretic properties, and was quickly introduced into medical practice
under the names of Antifebrin in 1886. But its (apparent) unacceptable toxic
effects, the most alarming being cyanosis due to methemoglobinemia and
ultimately liver and kidney damage, prompted the search for supposedly less toxic
aniline derivatives such as phenacetin. After several conflicting results over the
ensuing fifty years, it was established in 1948 that acetanilide was
mostly metabolized to paracetamol (acetaminophen) in the human body, and that it
was this metabolite that was responsible for the analgesic and antipyretic
properties. The observed methemoglobinemia after acetanilide administration was
ascribed to the small proportion of acetanilide that is hydrolyzed to aniline in the
body. Acetanilide is no longer used as a drug in its own right, although the success
of its metabolite – paracetamol (acetaminophen) – is well known (although it is
itself toxic in excessive amounts).
Mechanism of action
3
Required:
- Acetic acid/anhydride mixture, 20 ml
- Aniline 10 ml.
Procedure
1- Add 20 ml. of a mixture of equal volumes of acetic anhydride and
glacial acetic acid to 10 ml. (10.3 g.) of aniline contained in a 150 ml.
conical flask.
2- Fit a reflux water-condenser to the flask, and boil the mixture gently for
10 minutes.
3- Then pour the hot liquid into 200 ml. of cold water, stirring the latter
well
4- during the addition. The acetanilide rapidly crystallises. Filter at the
pump, and wash the crude acetanilide well with water.
5- Recrystallise from about 60 ml. of a mixture of one volume of acetic
acid and two volumes of water:
4
6- filter off the colourless crystals at the pump, again wash thoroughly with
water, drain, and dry. M.p. 113°.
calculations :
since the aniline is the limiting reagent , the yield should be calculated
from its amount taken .
- M.,wt of aniline = 93 g / mole
- M.wt of acetanilide = 135 g / mole
Theoretical yield :
1mole of aniline forms = 1 mole of acetanilide
93 g/mole of aniline form = 135 g/mole
Therefore , 10.3 g ( 10ml ) aniline = x g
X = (10.3 x 135 ) / 93
X= 14.95 g
Yield = practical wt. / theoretical wt x 100%
