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Preparation of Benzocaine by Acid-catalysed Esterification of a Carboxylic acid and Alcohol

(C9H11NO2 Mol.Wt. 165.2)

Theory:
When a carboxylic acid is heated with an alcohol in presence of mineral acid, e.g. sulphuric acid, hydrochloric acid or hydrogen chloride gas, the hydrogen atom of the carboxyl group is replaced by an alkyl group in the resulting product is called an ester. Hence, the reaction of a carboxylic acid with an alcohol to give an ester is known as esterification. When ethanol is heated with p-Amino benzoic acid in presence of Conc. sulphuric acid, Benzocaine (Ethyl p- amino benzoate) forms. This esterification is Fischer esterification.

H2N
p-Amino benzoic acid

+
Ethanol

H2SO4

+ H2 O Benzocaine(Ethyl p-amino benzoate)

Procedure:
Weigh and transfer 3.0g of p-Amino benzoic acid in a R.B. flask, then add 30ml of absolute ethanol. Shake well to dissolve the solid. Add 3ml of sulphuric acid dropwise into the ethanol-amino benzoic acid solution. A solid precipitates out of the solution. Attach a condenser to the round bottom flask , and set up the apparatus for heating under reflux. Connect the condenser to tap water supply. Heat the solution on a heating mantle under gentle reflux for approximately 30 minutes. Start heating slowly. Adjust the heat to keep the solution refluxing, but not boiling violently. Refluxing is confirmed when liquid droplets form at the tip of the condenser where the condenser is attached to the round bottom flask. If any solid precipitate remains after heating, take the condenser off of the round bottom flask and remove the round bottom flask from the heating mantle. Cool the solution at room temperature for 3-5 minutes. Add 9ml of absolute ethanol and 1.5ml of sulfuric acid (dropwise) to the round bottom flask containing the solution and precipitate. Reattach the condenser to the round bottom flask, and resume heating under gentle reflux until all of the solid has dissolved. It is very important for this experiment to succeed that ALL of the solids dissolve during this period. Once the solid is completely dissolved, continue heating the solution under gentle reflux for another 30 minutes.

Remove the round bottom flask from the heat source and allow the reaction mixture to cool to room temperature (7-10 minutes). Fill a 250mL beaker with 60ml of water and pour the cooled reaction mixture into the beaker. Basify the reaction mixture and water solution to a pH of about 8. To do this, calculate the approximate volume of 20% aqueous sodium carbonate required to neutralize the total amount of sulfuric acid you used (Usually between 27-36 ml). Slowly pour the calculated amount of 20% aqueous sodium carbonate into the beaker containing the reaction mixture and water solution. Be sure to add the sodium carbonate slowly as frothing occurs during neutralization . A solid should precipitate. This is crude benzocaine. Filter the mixture. Then transfer the crude benzocaine into a 125ml conical flask. Add about 60ml of water, then shake to mix properly. Heat the mixture to 60 C. Add minimum quantity of methanol (15-25ml) to dissolve the precipitates . Do not add more methanol than required. Then remove the flask from the heating source and allow the solution to cool to room temperature. It takes about 10 minutes. Cool the solution in an ice water bath for 15 minutes to complete crystallization of the benzocaine (white or colourless crystals) , then filter. Allow to dry the crystals. Finally calculate the yield and find out its m.p. (89.0 92)C.

Benzocaine