Fischer Esterification of p-aminobenzoic acid: Synthesis of Benzocaine

Adapted from the Revised Procedure: Expt. 21.1 Multistep Synthesis of Benzocaine Analogs
http://web.uccs.edu/bgaddis/chem338/expt21_1corr.htm

To a 100-mL round bottom flask fitted with a stir bar, add 2.50 g of p-aminobenzoic acid and 20
mL of ethyl alcohol. While stirring, add 2.0 mL of concentrated H2SO4 dropwise. The precipitate
that forms upon the addition of sulfuric acid should dissolve when the solution is heated.
Reflux, with stirring, for 1 hour. If you notice that the white suspension persist, add 1 additional
mL of concentrated H2SO4 dropwise. Cool to room temperature. Neutralize cautiously with
dropwise addition of 10% Na2CO3 until the pH is approximately 8. (Gas evolution will be
vigorous.) Extract with two 10-mL portions of methylene chloride. Wash the combined
methylene chloride layers with two 8-mL portions of water. Dry the methylene chloride
solution over anhydrous sodium sulfate. Gravity filter into a clean Erlenmeyer flask containing a
boiling stone. Evaporate the methylene chloride using the rotary evaporator. Recrystallize the
whitish residue using as a solvent pair, ethyl alcohol and water. Suction filter the product, and
let air dry. Weigh the white crystals and take the melting point. Perform IR spectroscopy and
compare the IR of the p-aminobenzoic acid to that of the product (collect 2 IR spectra: 1 of the
starting material and 1 of the product).

Prelaboratory Questions

Novocaine
1. Refer to the structure of Novocaine. Using p-aminobenzoic acid, propose a mechanism of
how Novocaine could be prepared.

2. Which of the two possible amino functional groups in Procaine would be protonated first?
Why?

3. What is the purpose of the sulfuric acid for this reaction? Is the acid consumed during the
synthesis?

Postlab Questions.
1. Write out the mechanism of your reaction. Tell what LeChatliers Principle is and how it
applies to this procedure. What is removed to drive the reaction to completion?

2. Why did you wash with aqueous sodium bicarbonate? Explain using balanced chemical
equations.

3. The oxygen from which material is incorporated into the new created ester bond? Where
does the oxygen in the product of water originate?
Benzocaine

This page contains recent news articles, when available, and an overview of Benzocaine but
does not offer medical advice. You should contact your physician with regard to any health
issues or concerns.

Overview:
Benzocaine (when available)

Pharmacology and use:

Benzocaine is a local anesthetic commonly used as a topical pain reliever. It is the active
ingredient in many over-the-counter analgesic ointments. It is also indicated for general use as
a lubricant and topical anesthetic on intratracheal catheters and pharyngeal and nasal airways
to obtund the pharyngeal and tracheal reflexes; on nasogastric and endoscopic tubes; urinary
catheters; laryngoscopes; proctoscopes; sigmoidoscopes and vaginal specula. For general use as
a lubricant and topical anesthetic on esophagus, larynx, mouth, nasal cavity, rectum,
respiratory tract or trachea, urinary tract, vagina. It is also used to suppress gag reflex.

Mechanism Of Action:
Benzocaine binds to sodium channel and reversibly stabilizes the neuronal membrane which
decreases its permeability to sodium ions. Depolarization of the neuronal membrane is
inhibited thereby blocking the initiation and conduction of nerve impulses.

Doctors unsure what causes canker sores - 20 Apr 2009

Liquids or ointments with a numbing ingredient, such as benzocaine (Anbesol, Oragel, Orabase,
Zilactin-B, Tanac) help relieve the discomfort of canker News-Leader.com

Family Doctor: Chiggers can spoil a day of outdoor fun - Apr 9, 2009
Its active ingredients are precipitated sulfur and benzocaine, which work together for quick
relief. It can also be used for mosquitoes, fleas, no-see-ums, Canton Repository

Collingham OAP stashed cocaine in washing machine - Mar 31, 2009

Police also found a 1kg bag of cocaine cutting agent Benzocaine in the tumble dryer at 65-year-
old Michael Hunter's home in Collingham near Wetherby. Yorkshire Evening Post

http://www.mongabay.com/health/medications/Benzocaine.html