The Hofmann Reaction

August Wilhelm Hofmann

            The Hofmann Amine Synthesis (also called the Hofmann Reaction or the Hofmann Degradation) enables the conversion of an amide into a primary amine. The preparation offered here is the conversion of ethanamide CH3CONH2 into aminomethane CH3NH2. Since the latter is a gas at room temperature, it is absorbed in hydrochloric acid so as to get the solid chloride salt CH3NH3+Cl-.


            Liquid bromine is a volatile brown liquid and is extremely toxic and corrosive, causing ulcerating burns that take a long time to heal. Sodium hydroxide is extremely caustic.

  • Dissolve 36g of sodium hydroxide in 160 cm3 of water contained in a 500 cm3 conical flask, and chill the stirred solution to 0-5oC in iced water.
  • Why does the solution need to be chilled?
  • The dissolution of sodium hydroxide is strongly exothermic; the liquid must not be hot since addition of bromine in the next step would be hazardous; it is very volatile and the reaction is exothermic.
  • Add 10.8 cm3 of bromine slowly to the stirred solution; during the addition the temperature rises slightly, and should be reduced again to 0-5oC.
  • Why is bromine added slowly?
  • The reaction is exothermic, and thermal runaway must be avoided.
  • Add a solution of 12 g of ethanamide in 20 cm3 of water, in small portions, to the stirred bromate(I) solution so that the temperature of the mixture does not rise above 20oC. Then remove the flask from the ice-water, and allow to stand at room temperature for 30 minutes.
  • Why is the ethanamide added slowly in small portions?
  • The reaction is exothermic.
  • Set up a distillation apparatus using a distilling flask of 500 cm3 capacity. Arrange for the outlet of the condenser to join via a short length of rubber tubing to an inverted funnel. The latter is arranged so that the rim is just below the surface of 100 cm3 of a solution of  2.5 mol dm-3 hydrochloric acid contained in a 250 cm3 beaker.
  • What is the function of the inverted funnel?
  • Aminomethane is very soluble in HCl; without the funnel the acid might suck back into the distillation apparatus. If suck-back does occur with the funnel, then the liquid drops below the rim and allows air in to equalise the pressure.
  • Transfer the reaction mixture to the distilling flask, add a few anti-bumping granules, and support the flask over a gauze. Heat the mixture cautiously so that the temperature rises slowly. When brisk effervescence occurs, remove the heat until the reaction subsides. Aminomethane is evolved and is absorbed by the hydrochloric acid solution. Continue to distil so that aminomethane is evolved smoothly and none escapes absorbtion by the hydrochloric acid. The distillation may be considered complete after 30 minutes.
  • What is the function of anti-bumping granules?
  • They provide nuclei on which gas bubbles can grow, leading to smooth boiling rather than bumping which can be hazardous.
  • Concentrate the solution of the amine chloride by distilling it until about 30 cm3 of liquid remains in the distilling flask. Transfer this residue to an evaporating basin, and evaporate to dryness over a boiling water bath.
  • Why is a boiling water bath used rather than direct heating with a flame?
  • The hydrochloride salt would decompose if heated too strongly, giving fumes of aminomethane and HCl which then recombine in the cool air as a white smoke.
  • Immediately break up the solid (a mixture of aminomethane hydrochloride and ammonium chloride) and transfer it to a 150 cm3 round-bottomed flask fitted with a reflux condenser. Add about 60-70 cm3 of absolute (i.e. completely water-free) ethanol and boil the mixture for 5 minutes. Pour the hot liquid through a fluted filter paper into a conical flask. Repeat the extraction with a further 20 cm3 of absolute ethanol and combine this with the previous extract. Cool the solution, and filter off the colourless crystals of the product. Transfer these rapidly to a desiccator.
  • Why must the ethanol be free from water?
  • Ammonium chloride is not soluble in absolute ethanol, but is fairly soluble in the usual laboratory reagent which contains some 5% of water.
  • Why is a fluted paper used?
  • The filtration is faster through a fluted paper.
  • Why is the product transferred rapidly to a desiccator?
  • The product is deliquescent and forms a solution rapidly with atmospheric moisture.