Preparation of Paracetamol | Synthesis of Paracetamol

Theoretical Background / Context

The general mechanism of the reaction between amino groups and the carboxylic group could be summarized as Follow:

• In this reaction, amines can act as nucleophiles, due to the fact they have the lone pair of electrons on the nitrogen atom.
• They have a partial negative charge which is attracted to an electrophile (has a partial positive charge), in this case, the polarised carbon atom (as it is bonded to the highly electronegative oxygen atom) on the acetic anhydride.
• Nitrogen begins its “attack” on the partially positive carbon.
• Because of the lone pair, it forms a dative covalent bond with the carbon.
• Because it is dative, the carbon atom has gained an electron therefore it has been reduced, so it then donates an electron within the double bond with oxygen to the oxygen atom, which makes the already partially negatively charged oxygen become negatively charged.
• There is now only a single bond between carbon and oxygen.
• The carbon atom then donates an electron to the oxygen below it that it is also singly bonded to, releasing an acetate ion (CH3COO), this has given the carbon atom that donated the electron a positive charge as it has now had a net loss of one electron from its original electron configuration.
• This is now a carbocation. The hydrogen then bonds to the ethanoate ion, forming ethanoic acid (CH3COOH) and ethanamide, ethan- the prefix coming from the two carbon atoms present and the suffix –amide due to the CONH functional group.
• The theoretical mechanism directly supports the preparation of paracetamol as performed in the experiment.

Principle of Work

Paracetamol has the molecular formula of C8H9NO2 as illustrated in the following structure:

The general equation of paracetamol synthesis is displayed in the following scheme:

Figure 1. Chemical Structure of Paracetamol

• The general equation of paracetamol synthesis is displayed in the following scheme:

Figure 2. Schematic Diagram for the Paracetamol Synthesis Reaction

• The mechanism for this reaction is a nucleophilic acyl substitution, with water as the solvent.
• The lone pair of electrons on the amine of the p-aminophenol attacks the C=O bond of the acetic anhydride, causing it to break and resulting in a positive charge on the nitrogen.
• The negative charge on the oxygen reforms the C=O bond, causing the other C-O bond to break.
• The positive nitrogen loses a proton when the negative oxygen attacks, forming acetic acid and leaving a paracetamol molecule.

Figure 3. Mechanism of Paracetamol Synthesis Reaction