Nitrogen Curtius rearrangement

The Curtius rearrangement can be catalyzed by Lewis acids or protic acids, but good yields are often obtained also without a catalyst. From reaction in an inert solvent (e.g. benzene, chloroform) in the absence of water, the isocyanate can be isolated, while in aqueous solution the amine is formed. Highly reactive acyl azides may suffer loss of nitrogen and rearrange already during preparation in aqueous solution. The isocyanate then cannot be isolated because it immediately reacts with water to yield the corresponding amine. 

The origins of sonochemistry lie in the study of homogeneous systems and among the examples of early synthesis is the Curtius rearrangement which appeared in 1938 [34]. In this example benzazide gives nitrogen and phenyl isocyanate when sonicated in benzene (Eq. 3.1), and the rate is increased in comparison to the normal thermal reaction. This reaction was not fully investigated at the time and the observation that the reaction stopped after rapid initial steps was not explained. 

In contrast to the somewhat limited synthetic utility of nitrenes, there is an important group of reactions in which migration occurs to electron-deficient nitrogen. One of the most useful of these reactions is the Curtius rearrangement 16 This reaction has the same relationship to acylnitrene intermediates that the Wolff rearrangement does to acylcar-benes. The initial product is an isocyanate, which can be isolated or trapped by a nucleophilic solvent. 

Some azides are capable of the so-called Curtius rearrangement, which results in the formation of isocyanates with loss of nitrogen. 

This reaction is related to the Hofmann and Schmidt Reactions and the Curtius Rearrangement, in that an electropositive nitrogen is formed that initiates an alkyl migration. 

In both reactions, the alkyl group (R) gets transferred from the carbonyl group to the nitrogen to form an intermediate isocyanate (0=C=N-R). This is then hydrolysed by water to form carbon dioxide and the primary amine. The Curtius rearrangement has the advantage that nitrogen is lost as a gas that helps to take the reaction to completion. 

Acyl azides are easily handled by acetic acid-catalysed Curtius rearrangement which generates one mole of nitrogen per azide This can be done conveniently on a micro scale with no interference from such groups as nitro, nitroso, azoxy, azo, hydrazo, cyano, amido, imido, amino or ammonium. Diazo or A -nitroso groups do interfere. 

In the first transformation, the carboxylic acid moieties are converted to the corresponding isocyanates employing a Curtius rearrangement. This transformation starts with the formation of mixed anhydride 33 which is subsequently attacked by the azide anion to give acyl azide 34. Then, acyl azide 34 rearranges with the formation of isocyanate 35 and nitrogen. As isocyanate 35 is unstable to hydrolysis... 

Denmark, S. E., Dorow, R. L. The stereochemical course of migration from phosphorus to nitrogen in the photo-Curtius rearrangement of phosphinic azides (Harger reaction). J. Org. Chern. 1989, 54, 5-6. 

This is called the Curtius rearrangement. There is no evidence for the existence of the free nitrene in this reaction, unlike in the Wolff rearrangement where there is some evidence for the existence of the free carbene, so probably the steps are concerted in this case. The driving force for this reaction is the production of molecular nitrogen. This provides so much energy, that it is possible to harness it to expand an aromatic ring. Indicate the pathway that is followed when an aryl azide is heated with phenylamine. 

---