The Nierenstein reaction is an organic reaction describing the conversion of an acid chloride into a haloketone with diazomethane.^[1][2] It is an insertion reaction in that the methylene group from the diazomethane is inserted into the carbon-chlorine bond of the acid chloride.

Reaction mechanism

The reaction proceeds through a diazonium salt intermediate formed by nucleophilic acyl substitution of the chloride with diazomethyl anion. The chloride then displaces the diazo group in an SN2 reaction, with N₂ as the leaving group.

If excess diazomethane is present during the reaction, it can act as a base, abstracting a hydrogen from the diazonium-salt intermediate. The result is a neutral diazoketone, which does not react with the chloride. Instead, the byproduct, diazonium-methyl from the other diazomethane molecule, can be attacked by the chloride to produce chloromethane. The unreactive diazoketone can be re-activated and reacted by treatment with hydrogen chloride to give the normal Nierenstein product.

In some cases, even limiting the amount of diazomethane gives a reaction process that stalls via the neutral diazoketone pathway, requiring the addition of HCl gas to rescue it.^[3]

Scope

One original 1924 Nierenstein reaction:^[4]

and a reaction starting from benzoyl bromide going haywire with formation of the dioxane dimer:^[5]