Synthesis of Acetanilide Paracetamol Phenacetin

Acetanilide, Paracetamol, and Phenacetin are the class of antipyretic analgesics drugs. Antipyretic analgesics are the class of drug that relieves mild to moderate pain, such as headache, myalgia, and arthralgia, and also lower the body temperature in pyrexia, that is in situations when the body temperatures have been raised above normal. In therapeutic doses, they do not have any effect on normal temperature. These drugs exert their action on the heat-regulating centre in the hypothalamus. The common group of compounds that used as antipyretic analgesics drugs are---

1. Aniline and para aminophenol derivatives such as acetanilide, paracetamol, phenacetin etc.

2. Salicylic acid derivatives such as aspirin, salol, sodium salicylate etc.

3. Quinoline derivatives such as cinchophen, neocinchophen etc.

4. Pyrazolones and pyrazolodiones derivatives such as phenazone, aminophenazone, phenylbutazone etc.

5. N-arylanthranilic acids derivatives such as mefenamic acid, meclofenamate sodium etc.

Synthesis of acetanilide

Aniline is the starting material for the synthesis of acetanilide. When aniline is treated with acetic anhydride in the presence of sodium acetate acetanilide is obtained.

Synthesis of acetanilide

Synthesis of paracetamol

The reduction of nitrobenzene by zinc and ammonium chloride gives phenylhydroxylamine. When phenylhydroxylamine is treated with sulfuric acid it gives para aminophenol, para aminophenol can be acetylated by a mixture of acetic anhydride and glacial acetic acid to give paracetamol (acetaminophen).

Synthesis of paracetamol

Paracetamol causes antipyresis by exerting its action on the hypothalamic heat-regulating centre, and analgesia by enhancing the pain threshold profile appreciably. It is effective in a wide variety of arthritic and rheumatic condition involving musculoskeletal pain as well as the pain of headache, neuralgias, myalgias, and dysmenorrhea. It is particularly useful in aspirin-sensitive patients.

Synthesis of phenacetin

Para nitrophenol on reaction with ethyl bromide in the presence of sodium hydroxide gives para nitrophenetole, this para nitrophenetole is reduced by Fe in presence of HCl to give para phenetidine, the resulting para phenetidine is acetylated with acetic anhydride to yield the compound phenacetin.

Synthesis of phenacetin

It is an analgesic and an antipyretic with similar effectiveness as aspirin. It has greater potential for toxicity (hemolytic anemia and methemoglobinemia) than paracetamol. Phenacetin is mainly used for mild to moderate pain.