This document describes the synthesis of benzocaine from p-aminobenzoic acid. P-aminobenzoic acid is reacted with ethanol in the presence of hydrochloric acid via an esterification reaction to form ethyl p-aminobenzoate (benzocaine). The percentage yield of benzocaine obtained was 93.3%, close to the theoretical yield, and it has a melting point of 91°C. Benzocaine is used as a local anesthetic to relieve minor mouth pain.

1. E X P E R I M E N T 3
M E D I C I N A L C H E M I S T R Y I
S Y N T H E S I S O F B E N Z O C A I N E F R O M P -
A M I N O B E N Z O I C A C I D
P R E S E N T E D B Y… .
P R O F. S O N A L I R . PA W A R
M E D I C I N A L C H E M I S T R Y I
B . P H A R M A C Y I V S E M E S T E R

2. Aim: To synthesize and characterized Benzocaine from P-amino benzoic acid.
Procedure: Place 13 ml of absolute ethanol in a 250-ml two-necked flask equipped with a double surface
reflux condenser and a gas inlet tube. Pass dry hydrogen chloride (13) through the alcohol until saturated - the
increase in weight is about 20 g - remove the gas inlet tube, introduce 2 gm (0.088 mol) of p-aminobenzoic
acid and heat the mixture under reflux for 2 hours. Upon cooling, the reaction mixture sets to a solid mass of
the hydrochloride of ethyl p-aminobenzoate. It is better, however, to pour the hot solution into c. 300 ml of
water (no hydrochloride separates) and add solid sodium carbonate carefully to the clear solution until it is
neutral to litmus. Filter off the precipitated ester at the pump and dry in the air. The yield of ethyl p-
aminobenzoate, m.p. 91 °C, is g (69%). Recrystallisation from rectified (or methylated) spirit does not affect
the m.p.

3. Chemical Reaction:
H2N COOH
C2H5OH
HCl
H2N COOC2H5
p-amino benzoic acid Ethyl-p-amino benzoate
(Benzocaine)
Principle:
 Synthesis of Benzocaine (Ethyl-p-amino benzoate) is based upon the principle of acid catalyzed
esterification reaction.
 When carboxylic acid is boiled with an alcohol in presence of concentrated sulfuric acid or dry
HCl gas, an ester forms.
 Acid catalyzes the reaction as well as absorbs the water formed in the reaction.

4.  Esterification is the process of combining an organic acid (RCOOH) with an alcohol (ROH) to form
an ester (RCOOR) and water; or a chemical reaction resulting in the formation of at least one ester
product. Ester is obtained by an esterification reaction of an alcohol and a carboxylic acid.
 In step 1 common reduction of aromatic para-nitrobenzoic acid by tin and
hydrochloric acid to para-aminobenzoic acid
 In step 2 esterification of para-aminobenzoic acid by sulphuric acid and ethanol
to benzocaine occurring called Fischer esterification.
 Example: CH3-COOH + CH3-CH2-OH →Acid CH3-COO-CH2-CH3 + H2O.
Ethanoic acid Ethanol Ethyl ethanoate (Ester) This reaction is known as esterification reaction.
[Ref: B. S. Furniss, A. J. Hannaford, P. W. G. Smith, Vogel’s textbook of practical organic chemistry, 5th
edition, Copublished in the United States with John Wiley & Sons, Inc., New York Page No. 897
Sachin Kumar Ghosh, Advanced General Organic Chemistry A Modern Approach, Published by New Central
Book Agency (P) Ltd., Kolkata, 2nd edition, Page No. 1016]

5. H2N OH
C
O
H
-H
H2N OH
C
OH
H2N OH
C
OH
C2H5OH
H2N OH
C
OH
O
H
C2H5
H2N OH2
C
OH
O
C2H5
H2N
-H2O
H2O
C
O OH
O C2H5
H
-H
H2N C
O
O C2H5

6.  Benzocaine is used short term to relieve pain from minor mouth problems (such as toothache,
canker sores, sore gums/throat, mouth/gum injury).
 It is a local anesthetic that works by numbing the painful area.
 Do not use this product for children younger than 2 years due to risk of serious side effects.

7. CALCULATIONS :-
Molecular weight of PABA= 137gm/M
Molecular weight of benzocaine = 165gm/M
Weight taken of PABA=2gm/M
Practical yield =2.24gm
X(theoretical yield )=molecular weight benzocaine x weight of PABA
taken
molecular weight of PABA
=165g/M x 2g/137g/M = 2.41gm
Percentage yield = practical yield /theoretical yieldx100%
Percentage yield =2.24/2.41x100%
Percentage yield = 93.3%

8. Calculation:
TLC:
Structure:
Formula: C9H11O2N
Theorotical Yield: 2.41gm
Practical Yield: 2.24gm
% Yield: 93.3%
Melting/Boiling
Point:
3100c/900c
Rf Value: 0.34