Nierenstein reaction explained

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 displacement of the chloride with diazomethyl anion.

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]

See also

Notes and References

  1. Clibbens, D. . Nierenstein, M. . The action of diazomethane on some aromatic acyl chlorides . . 1915 . 107 . 1491 . 10.1039/CT9150701491.
  2. Bachman, W. E. . Struve, W. S. . The Arndt-Eistert Reaction . Org. React. . 1942 . 1 . 38 . Werner Emmanuel Bachmann . (Review)
  3. McPhee, W. D; Klingsberg, E. Organic Syntheses, Coll. Vol. 3, p.119 (1955); Vol. 26, p.13 (1946). (Article)
  4. The Action of Diazomethane on some Aromatic Acyl Chlorides II. Synthesis of Fisetol . M. Nierenstein . D. G. Wang . J. C. Warr . amp . . 46 . 11 . 2551–2555 . 1924 . 10.1021/ja01676a028 .
  5. The Action of Diazomethane on some Aromatic Acyl Chlorides III. The Mechanism of the Reaction . H. H. Lewis . M. Nierenstein . Enid M. Rich . amp . . 47 . 6 . 1728–1732 . 1925 . 10.1021/ja01683a036.