Comparative Analysis of Paracetamol Essay Example

had taken phenacetin and in 1889, paracetamol was also shown to be a urinary metabolite of acetanilide. However, it was not until 1948 that Brodie and Axelrod established that paracetamol was a major metabolite of both phenacetin and acetanilide.

This, and other work, led to the belief that the clinical effect of these two drugs was entirely due to rapid conversion in the body to paracetamol. This belief was supported by the observation that the analgesic and antipyretic effects of paracetamol were of the same order as those of its parent compound. Some years later, it was shown that phenacetin had both effects in its own right and that paracetamol formation was not essential for its pharmacological action. However, because a very high proportion is converted to paracetamol during first passage through the liver, phenacetin itself exerts a direct analgesic effect only at very high doses.

The work of Brodie and Axelrod led to the introduction of 500 mg tablets of paracetamol in the United Kingdom in 1956, primarily as a prescription product. In 1963, paracetamol was added to the British Pharmacopoeia and its popularity as an over-the-counter analgesic increased rapidly. Subsequently, it also became an ingredient of compound analgesics, being combined with such centrally-acting compounds as codeine, dihydrocodeine and dextropropoxyphene, as well as with oral decongestants in a variety of formulations for the relief of the symptoms of the common cold, influenza and sinusitis.

Synthesis

Compared with many other drugs, paracetamol is much easier to synthesize, because it lacks stereocenters. As a result, there is no need to design a stereo-selective synthesis. Industrial preparation of paracetamol usually proceeds from nitrobenzene.

A one-step reductive acetamidation reaction can be mediated by thioacetate. Paracetamol may be easily prepared in the laboratory by nitrating phenol with sodium nitrate, separating the desired p-nitrophenol from the ortho- byproduct, and reducing the nitro group with sodium borohydride. The resultant p-aminophenol is then acetylated with acetic anhydride. In this reaction, phenol is strongly activating, thus the reaction only requires mild conditions.