Synthesis of Benzocaine Pharmacist Omar abdulrahman Pharmaceutical Chemistry Department College Of Pharmacy-HMU

Benzocaine: is a local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products for oral ulcers. It is also combined with antipyrine to relieve ear pain and remove earwax.

Chemical Structure of bezocaine

Local anesthetic agents conform to a similar molecular configuration consisting of a lipophilic aromatic ring connected to hydrophilic amine group . The linking chain may be used to classify the agents as an ester, amide, ketone or ether. Other molecules without this structure may also have local anaesthetic properties, but are not used clinically in this role (e.g. atropine, propranolol ) Ester and amides have achieved popularity in clinical practice.

Esters include cocaine, procaine, 2-chloroprocaine, tetracaine and benzocaine. Amides include lidocaine, bupivacaine, levobupivacaine, and articaine.

Chemistry of local anesthetic The basic chemical structure of a local anesthetic molecule consists of 3 parts: 1. Lipophilic group- an aromatic group, usually an unsaturated benzene ring. 2. Intermediate bond- a hydrocarbon connecting chain, either an ester (-CO-) or amide (-HNC-) linkage. The intermediate bond determines the classification of local anesthetic. 3. Hydrophilic group- a tertiary amine and proton acceptor.

Physiochemical property of benzocaine Benzocaine is sparingly soluble in water; it is more soluble in dilute acids and very soluble in ethanol, chloroform and ethyl ether. The melting point of benzocaine is 88-90 C, and the boiling point is about 310 C.

Chemical synthesis Benzocaine is the ethyl ester of p-aminobenzoic acid (PABA); it can be prepared from PABA and ethanol by fischer esterification or via the reduction of ethyl p-nitrobenzoate.

Reduction of ethyl p-nitrobenzoate

Procedure Add 1.20 g of p-amino benzoic acid and 12.0 ml of ethanol to a round-bottom flask with a magnetic stirbar. Left the mixture to stir until the solid dissolved. Add 1.0 ml of conc. Sulfuric acid slowly and allow the mixture to boil gently under reflux for about 75 minutes. Allow the mixture to cool and transfer it to a beaker containing 30 ml of water. 10% sodium carbonate solution was added until gas was no longer evolved. Filter the precipitate and calculate the percent of yield.