The Synthetic Routes of Atovaquone

Atovaquone is an antimalarial drug that is used to treat malaria.
It is synthesized through several different routes in the chemical industry, and the choice of route depends on factors such as cost, availability of raw materials, and the desired purity of the final product.

One of the most common synthetic routes for atovaquone involves a sequence of chemical reactions known as the Pichiah-Burley sequence.
This sequence involves the conversion of chloroacetophenone (1) to the alcohol (2) through a series of reactions, including electrophilic substitution, electrophilic addition, and reduction.

The alcohol (2) is then converted to the ketone (3) through a reaction known as hydrolysis.
This reaction involves the removal of water (H2O) from the alcohol (2) to form the ketone (3).

The ketone (3) is then reduced to the aldehyde (4) through a reaction known as reduction.
This reaction involves the addition of hydrogen (H2) to the ketone (3) to form the aldehyde (4).

The aldehyde (4) is then converted to the amide (5) through a reaction known as alkylation.
This reaction involves the addition of an alkyl halide (R-X) to the aldehyde (4) to form the amide (5).

Finally, the amide (5) is converted to the final product, atovaquone, through a series of reactions that involve the removal of the protecting groups and the formation of the desired ring structure.

Overall, the Pichiah-Burley sequence is a widely used synthetic route for atovaquone, and it provides a reliable and efficient way to synthesize this important antimalarial drug.