Making aspirin

Section 2 of 4

In the lab, salicylic acid meets ethanoic anhydride, with a few drops of acid as a catalyst. Warm them together, and aspirin forms.

Ethanoic anhydride is two ethanoyl groups joined through one oxygen atom. Its name tells you where it comes from: anhydride means "without water", and the molecule is two ethanoic acid molecules joined with one water molecule taken out, the same kind of condensation that makes an ester.

Ethanoic anhydride (acetic anhydride), (CH₃CO)₂OTwo ethanoyl groups, each a methyl group on a carbon with a double-bonded oxygen, joined through one oxygen atom in the middle.HOOHHCCOCCHHH
Ethanoic anhydride, (CH₃CO)₂O: two ethanoyl groups joined through one oxygen atom. It is a colourless liquid that smells strongly of vinegar.

Why the anhydride

Salicylic acid's -⁠OH sits on a benzene ring, and an -⁠OH on a ring joins ethanoic acid only slowly. That reaction also gives off water, and water can split the new ester apart again, so the mixture stops part of the way. Ethanoic anhydride reacts much faster. Its leftover half comes off as ethanoic acid, which leaves the ester alone, so the reaction goes almost all the way to aspirin.

Salicylic acid, C₇H₆O₃A benzene ring carrying a -COOH group and, on the next corner, an -OH group.OHOHO plus Ethanoic anhydride (acetic anhydride), (CH₃CO)₂OTwo ethanoyl groups, each a methyl group on a carbon with a double-bonded oxygen, joined through one oxygen atom in the middle.OOO
make
Aspirin, C₉H₈O₄A benzene ring carrying a -COOH group and, on the next corner, an oxygen joined to a two-carbon piece with a double-bonded oxygen.OOHOO plus Acetic acid (ethanoic acid), CH₃COOHTwo carbon atoms; the second carbon has a double bond to one oxygen atom and a single bond to an -OH group.OHO
Salicylic acid and ethanoic anhydride make aspirin and ethanoic acid: C₇H₆O₃ + (CH₃CO)₂O → C₉H₈O₄ + CH₃COOH. The ethanoyl group moves from the anhydride onto salicylic acid's -⁠OH.
Atoms on each side when aspirin forms
AtomC₇H₆O₃ + C₄H₆O₃C₉H₈O₄ + C₂H₄O₂
carbon7 + 4 = 119 + 2 = 11
hydrogen6 + 6 = 128 + 4 = 12
oxygen3 + 3 = 64 + 2 = 6

The catalyst is a few drops of concentrated sulfuric or phosphoric acid. Its H⁺ joins the oxygen of one of the anhydride's C=O groups. That oxygen then pulls electrons harder, so its carbon becomes more δ+, and the lone pair on salicylic acid's -⁠OH oxygen reaches it faster. At the end the H⁺ comes off again, ready for the next molecule, as a catalyst does.

In the flask

  1. Salicylic acid crystals, ethanoic anhydride and the drops of acid go into a flask.
  2. The flask sits in a bath of hot water for about 15 minutes, and the crystals dissolve as they react.
  3. Cold water goes in. It turns the leftover ethanoic anhydride into ethanoic acid.
  4. The flask goes into ice. Aspirin dissolves poorly in cold water, so it comes out of the liquid as white, needle-like crystals.
  5. The crystals are filtered off, washed with ice-cold water and dried.

Quick check

Salicylic acid reacts with ethanoic anhydride. What else is made along with aspirin?