Curtius rearrangement reactions

To this point has been called the Curtius Rearrangement /Reaction... 

Synthetic routes for preparing previously unknown 2,5-diamide-substituted furans by exploiting Curtius rearrangement reactions were described (14EJ05487). 

Phosgenation of N,N-bis(trimethylsilyl)amine is superior to the use of methylamine. The Curtius rearrangement reaction effectively produces the labeled methylisocyanate but is very time consuming and results in a low radiochemical yield. 

In a second example, the Lessen rearrangement was utilized in the scale-up synthesis of neutrophil elastase inhibitor, ONO-6868, circumventing the need for a potentially explosive Curtius rearrangement reaction. Lessen transformation of 43 using 0-acetylated hydroxamate took place in refluxing THF/H2O condition. The yield for the rearrangement itself was not provided, however, the overall yield for conversion of 43 to 45 was reported to be 63%. ... 

Baumann, M., Baxendale, I.R., Ley, S.V., Nikbin, N., Smith, C.D., and Tierney, J.P. (2008) Azide monoliths as convenient flow reactors for efficient Curtius rearrangement reactions. Org. Biomol Chem., 6, 1587-1593. 

The thermal decomposition of acyl azides into isocyanate intermediates is known as Curtius rearrangement reaction (Scheme 5.2) [27, 28]. Conventionally used general methods to synthesize aroyl azides are limited to diazotization of hydrazides and reactions of NaNs with acid chlorides, mixed anhydrides, and Al-acyl benzotriazoles [35-38]. However, these procedures involve highly reactive chemicals which put significant limitations on functionalities of the substrate. The development of methodologically new, highly functional-group tolerant, catalytic routes to aroyl azides is particularly desirable. 

The Curtius rearrangement in acetic anhydride of the azide (8) prepared from 4-carboxythiazole yields 4-acetamidothiazole (Scheme 8) (47). The same reaction starting with ethyl-2-methyl-4-thiazolyl carboxy-late, failed to give the 4-aminothiazole (48). Heterocyclizations are more convenient synthetic methods (Chapter II. Table 40). 

A related reaction sequence, which proceeds through a Curtius rearrangement, allows the transformation of a-cyano acids into hydantoins (66) ... 

If primary or secondary amines are used, A/-substituted amides are formed. This reaction is called aminolysis. Hydra2ines yield the corresponding hydra2ides, which can then be treated with nitrous acid to form the a2ides used in the Curtius rearrangement. Hydroxylamines give hydroxamic acids. 

The thermal decomposition of an acyl azide 1 to yield an isocyanate 2 by loss of N., is called the Curtius reaction - or Curtius rearrangement. It is closely... 

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. 

An isocyanate 2 formed by a Curtius rearrangement can undergo various subsequent reactions, depending on the reaction conditions. In aqueous solution the isocyanate reacts with water to give a carbaminic acid 6, which immediately decarboxylates to yield an amine 3. When alcohol is used as solvent, the isocyanate reacts to a carbamate 7 ... 

Acyl azides can undergo photolytic cleavage and rearrangement upon irradiation at room temperature or below. In that case acyl nitrenes 8 have been identified by trapping reactions and might be reactive intermediates in the photo Curtius rearrangement. However there is also evidence that the formation of isocyanates upon irradiation proceeds by a concerted reaction as in the case of the thermal procedure, and that the acyl nitrenes are formed by an alternative and competing pathway " ... 

The Curtius rearrangement, like the Hofmann rearrangement, involve migration of an -R group from the G-O carbon atom to the neighboring nitro gen with simultaneous loss of a leaving group. The reaction takes place on heat ing an acyl azide that is itself prepared by nucleophilic acyl substitution of m acid chloride. 

Curtius rearrangement, 933 diazotization reaction, 941 Gabriel amine synthesis, 929 heterocycle, 945... 

Curtius rearrangement (Section 24.6) The conversion of an acid chloride into an amine by reaction with azide ion, followed by heating with water. 

Claisen rearrangement, 660 conjugate carbonyl addition reaction, 725-726 Curtius rearrangement, 935 cyanohydrin formation, 707 dichlorocarbene formation, 227 Dieckmann cyclization reaction, 892-893... 

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 Curtius rearrangement involves the pyrolysis of acyl azides to yield isocy-anates. " The reaction gives good yields of isocyanates, since no water is present to... 

This version of the Curtius rearrangement has been applied to the synthesis of amino acid analogs and structures containing amino acids. Several m-2-aminocyclopropane carboxylate esters were prepared by selective hydrolysis of cyclopropane-1,2-dicarboxylates, followed by reaction with DPPA.267... 

Section A of Scheme 10.15 contains a number of examples of Curtius rearrangements. Entry 1 is an example carried out in a nonnucleophilic solvent, permitting isolation of the isocyanate. Entries 2 and 3 involve isolation of the amine after hydrolysis of the isocyanate. In Entry 2, the dihydrazide intermediate is isolated as a solid and diazotized in aqueous solution, from which the amine is isolated as the dihydrochloride. Entry 3 is an example of the mixed anhydride procedure (see p. 948). The first stage of the reaction is carried out in acetone and the thermolysis of the acyl azide is done in refluxing toluene. The crude isocyanate is then hydrolyzed in acidic water. Entry 4 is a reaction that demonstrates the retention of configuration during rearrangement. 

The pyrido[l,2-tf][l,3,5]triazine-2,4(3//)-dione derivative 89 was obtained in a cycloaddition reaction of diphenyl-methyl isocyanate 90 with 2-pyridyl isocyanate 91 derived from the corresponding acyl azide via Curtius rearrangement <2002ARK438>. Compound 89 was also synthesized by the reaction of diphenylacetyl chloride 118 and picolinyl azide 116a in the presence of triethylamine (Scheme 11) <2002ARK438>. ... 

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