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Concept
Curtius rearrangement
Summary
The Curtius rearrangement (or Curtius reaction or Curtius degradation), first defined by Theodor Curtius in 1885, is the thermal decomposition of an acyl azide to an isocyanate with loss of nitrogen gas. The isocyanate then undergoes attack by a variety of nucleophiles such as water, alcohols and amines, to yield a primary amine, carbamate or urea derivative respectively. Several reviews have been published.
The acyl azide is usually made from the reaction of acid chlorides or anydrides with sodium azide or trimethylsilyl azide. Acyl azides are also obtained from treating acylhydrazines with nitrous acid. Alternatively, the acyl azide can be formed by the direct reaction of a carboxylic acid with diphenylphosphoryl azide (DPPA).
It was believed that the Curtius rearrangement was a two-step processes, with the loss of nitrogen gas forming an acyl nitrene, followed by migration of the R-group to give the isocyanate. However, recent research has indicated that the thermal decomposition is a concerted process, with both steps happening together, due to the absence of any nitrene insertion or addition byproducts observed or isolated in the reaction. Thermodynamic calculations also support a concerted mechanism.
The migration occurs with full retention of configuration at the R-group. The migratory aptitude of the R-group is roughly tertiary > secondary ~ aryl > primary. The isocyanate formed can then be hydrolyzed to give a primary amine, or undergo nucleophilic attack with alcohols and amines to form carbamates and urea derivatives respectively.
Research has shown that the Curtius rearrangement is catalyzed by both Brønsted and Lewis acids, via the protonation of, or coordination to the acyl oxygen atom respectively. For example, Fahr and Neumann have shown that the use of boron trifluoride or boron trichloride catalyst reduces the decomposition temperature needed for rearrangement by about 100 °C, and increases the yield of the isocyanate significantly.
Photochemical decomposition of the acyl azide is also possible.
Official source
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Related concepts (4)
Schmidt reaction
In organic chemistry, the Schmidt reaction is an organic reaction in which an azide reacts with a carbonyl derivative, usually an aldehyde, ketone, or carboxylic acid, under acidic conditions to give an amine or amide, with expulsion of nitrogen. It is named after Karl Friedrich Schmidt (1887–1971), who first reported it in 1924 by successfully converting benzophenone and hydrazoic acid to benzanilide. The intramolecular reaction was not reported until 1991 but has become important in the synthesis of natural products.
Hofmann rearrangement
The Hofmann rearrangement (Hofmann degradation) is the organic reaction of a primary amide to a primary amine with one less carbon atom. The reaction involves oxidation of the nitrogen followed by rearrangement of the carbonyl and nitrogen to give an isocyanate intermediate. The reaction can form a wide range of products, including alkyl and aryl amines. The reaction is named after its discoverer, August Wilhelm von Hofmann, and should not be confused with the Hofmann elimination, another name reaction for which he is eponymous.
Rearrangement reaction
In organic chemistry, a rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. Often a substituent moves from one atom to another atom in the same molecule, hence these reactions are usually intramolecular. In the example below, the substituent R moves from carbon atom 1 to carbon atom 2: Intermolecular rearrangements also take place.