Working backwards

Section 1 of 4

To make a molecule, chemists start at the end. They draw the molecule they want, the target, and work backwards, step by step, to molecules they can buy.

Each step backwards cuts one bond in the target: a bond that a known reaction can make. The cut leaves two smaller pieces. When both pieces can be bought, the plan is complete. When one cannot, the chemist cuts that piece too, and carries on until every piece is something on a chemical supplier's shelf. Working backwards like this is called retrosynthesis, and chemists draw each step with a hollow, double-lined arrow, ⇒, which means "can be made from".

Cutting aspirin

Aspirin is salicylic acid with an ethanoyl group, -⁠COCH₃, joined to its -⁠OH. An ester link, -⁠COO⁠-, the link that forms when an acid and an alcohol join, holds the two together. Chemists know how to make ester links, so that is the bond to cut.

Working backwards from aspirin Left: aspirin, a benzene ring carrying a -COOH group and, on the next corner, an oxygen joined to an ethanoyl group drawn in amber. A wavy line cuts the bond between that oxygen and the ethanoyl group's carbon: cut the ester link. A hollow, double-lined arrow points right, meaning can be made from. Right: salicylic acid, the same ring with an -OH group where the cut was, plus the amber ethanoyl group, a carbon with a double-bonded oxygen and a methyl group, and a dotted free bond where it joins on. OOHOO aspirin cut the ester link OOHOH salicylic acid + O ethanoyl group
Working backwards from aspirin. Cutting the ester link gives salicylic acid and an ethanoyl group (amber). The ethanoyl group has a free bond, so it needs a molecule to carry it.

Salicylic acid comes in a jar. The ethanoyl group, with its free bond, cannot sit in a bottle on its own, so the chemist picks a molecule that carries one and can hand it over. Ethanoic acid carries an ethanoyl group, and so does ethanoic anhydride, the one chemists use for aspirin. The next section shows why.

Further back

A lab buys its salicylic acid, so its plan stops here. The factories that make salicylic acid go further back. Its -⁠COOH group comes from carbon dioxide. Sodium hydroxide first turns phenol, a benzene ring with one -⁠OH group, into its sodium salt; carbon dioxide then joins the ring under heat and pressure, and an acid gives salicylic acid. Phenol in turn is made from benzene, which comes from crude oil. Each of those steps is a cut that chemists know how to put back together.

Phenol, C₆H₅OHA benzene ring carrying one -OH group.OH
Phenol, C₆H₅OH, the simplest of the phenols: a benzene ring with one -⁠OH group. Once sodium hydroxide has turned it into its salt, carbon dioxide joins its ring on the corner next to the oxygen, and this leads to salicylic acid.

Quick check

A chemist plans to make the ester ethyl ethanoate, the sweet-smelling liquid in some nail polish removers. Working backwards, which cut gives two pieces that are easy to buy?