Curtius rearrangement mechanism

Carboxylic acid derivatives can be converted into primary amines with loss of one carbon atom by both the Hofmann rearrangement and tire Curtius rearrangement. Although the Hofmann rearrangement involves a primary-amide and the Curtius rearrangement involves an acyl azide, both proceed through similar mechanisms. 

The actual product of the reaction is thus the ketene, which then reacts with water (15-3), an alcohol (15-5), or ammonia or an amine (15-8). Particularly stable ketenes (e.g., Ph2C=C=0) have been isolated and others have been trapped in other ways (e.g., as P-lactams, 16-64). The purpose of the catalyst is not well understood, though many suggestions have been made. This mechanism is strictly analogous to that of the Curtius rearrangement (18-14). Although the mechanism as shown above involves a free carbene and there is much evidence to support this, it is also possible that at least in some cases the two steps are concerted and a free carbene is absent. 

The thermal Curtius rearrangement of formyl, acetyl, and benzoyl azides was studied by DFT.78 The authors conclude that the reaction occurs by a concerted mechanism and not by the alternative nitrene intermediate. 

The isocyanate can he isolated if the Curtius degradation is carried out in an inert solvent. The isocyanate also can be reacted with a heteroatom-nucleophile either subsequently or in situ. The heteroatom nucleophile adds to the C=N double bond of the isocyanate via the mechanism of Figure 8.12. In this way, the addition of water initially results in a carbamic acid. However, all carbamic acids are unstable and immediately decarboxylate to give amines (see Figure 8.5). Because of this consecutive reaction, the Curtius rearrangement represents a valuable amine synthesis. The amines formed contain one C atom less than the acyl azide substrates. It is due to this feature that one almost often refers to this reaction as Curtius degradation, not as Curtius rearrangement. 

The following reaction is known as the Curtius rearrangement. Its mechanism is similar to the Hofmann rearrangement. Show the mechanism of this reaction. 

The Curtius rearrangement starts with an acyl azide and occurs by a mechanism very similar to that of the Hofmann rearrangement. 

From the above general discussion, it is obvious that the proposed mechanisms of the Curtius rearrangement must be regarded as tentative. In particular, measurements of lifetimes and rates of intersystem crossing of intermediate nitrenes, coupled with spectroscopic data on the available excited states of acyl azides, should resolve the problem. 

The rearrangement has a mechanism similar to those of the Hofmann rearrangement of amides, the Lossen rearrangement of acylhydroxamic esters, the Schmidt rearrangement of carbonyl compounds and the Wolff rearrangement of diazoketones. Evidence concerning the mechanism of one can often be applied to the others, and the whole family has been reviewed briefly . Sometimes the distinction is made that the conversion of an acyl azide into an isocyanate or urethane is the Curtius rearrangement whereas the overall sequence is the Curtius reaction, but usually the former name is used for both processes. 

The outstanding thermal reaction of the acyl azides is their rearrangement to isocyanates. This Curtius rearrangement occurs also in the photodecomposition of the acyl azides, but the yield of isocyanate is lower than in the corresponding thermal process, and other products appear which can be accounted for by a nitrene precursor. A considerable amount of work has been directed towards an elucidation of the mechanism of the photo-Curtius rearrangement and the bulk of the evidence seems to favour the view that it ° is a concerted process not involving a discrete nitrene intermediate. Nitrenes are nevertheless formed in the photolysis of acyl azides and the products of this alternative route will now be discussed. 

Lwowski s work on pivaloyl azide has some interesting implications for the mechanism of the photo-Curtius rearrangement photolysis of pivaloyl azide in a variety of solvents results invariably in about 40% isocyanate, irrespective of the medium in which the reaction is conducted. Even in mixed solvents the isocyanate yield is hardly affected... 

Problem 24.11 Show the mechanism of the Curtius rearrangement of an acyl azide to an isocyanate. 

Batori, S., Messmer, A., Timpe, H. J. Condensed as-triazines. Part XI. Photoinduced fragmentation of pyrido[2,1-f]-as-triazinium-4-olate and its benzolog. Mechanism of Curtius rearrangement. Heterocycles, 32, 649-654. 

From CFa-COCl + NaNa- CFj CO Na- -CFs NCO. Curtius rearrangement of iri-fluoroacetyl azide, which tends to detonate when subjected to thermal or mechanical shock, was effected at 120 °C in CHCl, the isocyanate thus obtained was contaminated with up to 25%ofCF,-N CF,.> ... 

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