Synthesis of Benzocaine

% yield =            =

                                   =  69 % (2 S.F.)

4. Procedure:

No changes were made to the procedure given in CHEM3061 Laboratory Manual, p. 1-1 to 1-2.

5. Results:

Addition of concentrated sulfuric acid to the p-aminobenzoic acid, ethanol mix generated a white solid precipitate to form.

Addition of 10% sodium carbonate solution to the refluxed solution above caused effervescing to occur.

The product appeared to be a white crystalline solid, tabular, semi-transparent with moderate reflectivity, ~5mm in width.

Weight of product = 4.05 g                                % yield = 69 %

Melting point range = 88 – 89 °C                        Literature melting point = 89 °C

6. IR analysis:

7. 1H NMR Analysis

8. Discussion:

The reaction mechanism for the synthesis of benzocaine is divided into six key steps: (1) the protonation of the carbonyl by sulfuric acid to give a resonance stabilised intermediate; NH2 is also protonated (2) nucleophillic attack of the alcohol at the carbonyl carbon (3) loss of oxonium leaving group (4) proton transfer leading to a tetrahedral carbonyl addition intermediate (5) further proton transfer leading to a new oxonium ion and its subsequent loss giving (6) the acidified product, water and regeneration of the acid catalyst; finally the product is neutralised with sodium carbonate.

An acceptable yield of 69% of benzocaine was achieved in the present experiment; product may have been lost through (1) the reversible nature of each step in the reaction, although this was minimised by employing Le Chatelier’s principle (using excess ethanol) and (2) during refluxing, a loss of solvent would lead to a significant decrease in yield.

The identity of the synthesised compound was confirmed through IR and melting point analyses to be that of benzocaine. In particular, the obtained IR spectrum iterated the presence of structures such as a 1,4 di-substituted aromatic ring, primary aromatic amine, and an ester functional group directly attached to the aromatic ring as a result of lower frequency of the carbonyl than expected due to conjugation from the aromatic ring. Furthermore, the melting point range achieved (88-89°C) concurred well with the literature value of 89°C, confirming the purity of the obtained sample.