I Benzocant Do This Reaction

Fischer Esterification Preparation of Benzocaine

Arvind Narayan
Section 216-133
Luke Peterson, GSI
Fall 2013

Introduction
From phosphoesters that create the back bone of DNA, to esters used in fragrances from fatty
acids and oils, ester functionality is found in virtually every realm of science. Esters are organic
compounds that can only be synthesized from two organic other compounds: alcohol and an
acid. When these two compounds combine, it also creates the byproduct water. The purpose of
this experiment was to make Benzocaine by the process of classical Fischer esterification of paminobenzoic acid with ethanol. [1]
Esterification is highly reversible[2] therefore the removal of water helps keep the reaction in
favor of the products as described by LeChteliers principle. Sulfuric acid (H2SO4 ) works two
fold to catalyze the reaction as well as help stop the formation of water[2]. After the ester is
synthesized, IR spectra, TLC plates and melting point helped characterize the final product.
Reaction

cat. H2SO4

Reagents:
Compound

CAS Number

mol. wt.
(g mol-1)
137.14 --

Concentration
or Density

p-aminobenzoic acid

150-13-0

Ethanol (anhydrous)
Concentrated H2SO4

64-17-5
7664-93-9

46.07 200 proof

98.08 1.840 g/mL

Sodium Carbonate
solution

497-19-8

105.99 10% w/w aq

m.p. or
b.p. (C)
187
189
(mp)
78 (bp)
~ 290
(bp)
--

SAFETY
toxic, irritant

flammable
corrosive
strong acid
toxic

Experiemental Section
ethyl p-aminobenzoic acid. A 10 mL flask was filled with ethanol (3.60 mL, 17.1 M) and paminobenzoic acid (.360 g, 2.62 x 10-3 mol) was dissolved in the flask. A stirbar was added to
aid in the dissolution of the solid. Concentrated sulfuric acid (.30 mL, 16.6 M) was added drop
wise. A water-cooled condenser was attached and the solution boiled for 75 min. The solution
was then transferred with a Pasteur pipet to a flask containing 3 mL of water. Sodium carbonate
(10% w/w) was added dropwise until a precipitate formed. The ethyl p-aminobenzoic acid
precipitate was collected through vacuum filtration using a Hirsch funnel. Recrystallization using
hot ethanol was carried out. The product was left overnight to dry and recrystallize. IR (film)
3420, 3341, 3224, 1680, 1600 cm-1 . TLC Rf 0.571 (70:30 hexanes/ethyl acetate). Melting point
87-89.1 C.
Results and Discussion
The actual mass of reagent used was .3699 g dissolved in 3.60 mL of ethanol. The initial
reagents dissolved after stirring, but a precipitate, the hydrogen sulfate salt of p-aminobenzoic acid,
formed immediate after addition of the sulfuric acid. The pH of the solution was tested here to
check the acidity before the following reflux period. The pH of the solution used was between 2
and 3. When the sodium carbonate was added, the pH rose to 8 and a precipitate formed in the
solution. There were noticeable CO2 bubbles in the solution after the sodium carbonate was
added. The mass of the final product after the collection was .2339 g and after recrystallization
was .2160 g.
The percent is calculated, using the fact that the reaction is 1:1, in the following manner:

The actual mass recovered after the reaction was .2339 which resulted in a yield of
. This medium yield can be explained some product not being transferred to the flask
or a poor removal of water during the reflux process which led to led product created.
The Rf values helped to verify the polarity and purity of the compounds. The starting materials
value of .2 showed that it is very polar. The products value of .57 showed that it less polar that
the starting material. The cospot confirmed that a reaction happened because there is separation
between the starting material and the product.
The melting point showed that the compound melted around 87 89.1 C. This is less that the
literature value listed at 92 C for benzocaine. This could be explained by an incomplete reaction
and an impure product. It is also possible that there is water in the product which causes the
melting point to be skewed.
The IR confirms the identity of the starting material and the product. The peak at 2920 confirms
the hydroxyl group in the compound and the peak at 1680 confirms the carbonyl double bond.
The IR spectrum of the product shows peaks at 3341 for the nitrile group and a peak at 1680 for
the carbonyl bond. The distinct difference between the two spectra is the loss of the broad OH
peak for the p-aminobenzoic acid in the product. This confirms that a reaction happened at that
alcohol.
Conclusion
In conclusion, the melting point, TLC, and IR give solid evidence that the product formed in the
reaction is benzocaine. Although a low yield and a contaminated product was formed, there is
still enough to confirm that and esterification reaction took place.

Works Cited
1. Salkowski, Ber. 1895, 28, 1921 and Adams and Cohen, Org. Syn. Coll. Vol. I, 2nd ed.,
1932, p. 240
2. Roger J. Williams, Alton Gabriel, Roy C. Andrews The Relation Between the
Hydrolysis Equilibrium Constant of Esters and the Strengths of the Corresponding
Acids J. Am. Chem. Soc., 1928, volume 50, 1267