Thermal Curtius

The pyrrole derivative of carbonyl azide 206 undergoes thermal Curtius rearrangement into isocyanate, which spontaneously cyclizes into pyrrolo-diazepinone 207 (Equation (27) (1991JHC1911)). 

However, Lwowski and co-workers demonstrated that photolysis of 7 in cyclohexane, cyclohexene- or 2-methylbutane does lead to the formation of adducts. Therefore, the acylnitrene 8 is a trappable intermediate. The thermal Curtius rearrangement does not involve free nitrenes and it must be a concerted process. 

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. 

Triazole-based annelations have also been used to prepare 2-phenyl-2/7-[l,2,3]triazolo[4,5-e]py-ridin-4-one (233) from 2-(2-phenyl-l,2,3-triazole)acrylic acid via a thermal Curtius reaction of the a,/J-unsaturated acyl azide (232) (Scheme 43). Further functionalization of the nucleus was accomplished using the intermediate 2//-4-chlorotriazolo[4,5-c]pyridine (234) <85 LA 1922). 

The thermal Curtius reaction of a 3-aminopyrazine-2-carboxylic acid azide proceeds with intramolecular cyclization to provide a versatile synthetic route to a wide variety of 1,3-dihydro-2tf-imidazo[4,5-i]-pyrazin-2-ones. Many compounds in this series are potent hypotensive agents in animals they are also inhibitors of the enyzme cyclic AMP phosphodiesterase in vitro. 

Acyl azides are well-known compounds. Their role in the thermal Curtius rearrangement, a reaction that apparently does not involve a nitrene, will be discussed in subsection 8.3.2. Photochemical decomposition of acyl azides elidts nitrene reactivity. In particular, intramolecular C-H-insertion reactions have been observed, but not usually in high 5deld. ... 

We anticipated that a similar strategy would be applicable to the synthesis of l,3-oxazine-2,4-diones, involving the in situ formation of isocyanates by thermal Curtius rearrangement of acyl azides under the same conditions of the Wolff rearrangement. Indeed, tenperature-regulated microwave irradiation of a 1 1 mixture of a 2-diazo-1,3-diketone and an acyl azide afforded the desired l,3-oxazine-2,4-dione products 33 (Scheme 3.281. This sequence nicely illustrates the utilization of microwave activation for the selective one-pot thermal rearrangements of azido and diazo compounds. 

The thermal Curtius rearrangement of benzoyl azide in the presence of Lewis acids was studied using DFT. ... 

In 2010, Studer et al. reported A -heterocyclic carbene catalyzed oxidative amidations of various aldehydes to the corresponding acyl azides by using the readily available organic oxidant [43]. Acyl azides can readily be converted via thermal Curtius rearrangement to carbamoyl azides as shown for the transformation of benzaldehyde to phenyl carbamoylazide (Scheme 5.7), when r-BuOH was further added to the crude reaction mixture, which was then heated for 1 h to reflux. Therefore, a mild NHC-catalyzed oxidative azidation of aromatic aldehydes to form the corresponding acyl azides which can be rearranged to carbomoylazides in the same pot. 

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... 

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 reaction of Curtius, which is especially to be preferred in the case of the higher members on account of the favourable solubilities of the intermediate products, involves as its first stage the preparation of the hydrazide from an ester (or acid chloride). The hydrazide is then converted, usually very readily, by the action of nitrous acid into the azide. In many cases it is more convenient to prepare the azide by treating an acid chloride with sodium azide previously activated with hydrazine hydrate.1 Azides easily undergo thermal decomposition, the two azo nitrogen atoms being eliminated as elementary nitrogen. In this way, however, the same radicle is formed as was invoked above to explain the Hofmann reaction ... 

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 a related type of reaction, the styryl isocyanates, readily available by Curtius rearrangement of cinnamoyl azides, undergo thermal cyclization to l-isoquinolones in good yield (equation 34) the reaction can also be carrried out using Friedel-Crafts catalysts. 2,3-Dihydro-4( 1//)- isoquinolones are obtained by Dieckmann cyclization of N- (o- carbalkoxy-benzyl)glycine ester derivatives (equation 35). The same reaction has been used for the synthesis of a range of non-aromatic heterocycles (equations 36 and 37). 

The expl props, as detd by Haid et al (Ref 8), indicate that Ca azide is the most powerful of the alkaline earth azides. Although Curtius found that this salt did not expl by percussion, Wohler Martin (Ref 5) and Haid et al (Ref 8) obtained deton by impact (Refs 7 12). When heated rapidly Ca(Nj)3 expl between 144-156°. Heated in a capillary tube, metallic Ca appears at 120-130° (Ref 11) and in vacuo expl between 160-170° (Ref 14). The kinetics of the thermal decompn has been studied by Andreev (Ref 10), Garner Reeves (Ref 19) and others ionic conductance of the solid by Jacobs Tompkins (Ref 18) in the temp range 290-370°K, and initiation and propogation of expln by Bowden Williams (Ref 16) who measured the rate of deton as 770 m/sec. 

Eloy and Deryckere have applied their synthesis of isocarbostyrils (69HCA1755) to the preparation of thieno[2,3-c]- and thieno[3.2-c]-pyridines (Scheme 65) (70BSB301). Thermal-cyclization of 3-thienylvinyl isocyanate prepared from the corresponding azide (269) by Curtius rearrangement yields thieno[2,3-c]pyridin-7-one (270), which is transformed to (259) following usual methods. 

Compound 610 was transformed thermally to the tetrazolo[5,l-b]purin-7(8//)-one 639 through Curtius rearrangement via the isocyanate intermediate 638 (86H1899). Reaction of 626 (R = Ph) with bromine or sulfuryl chloride led by ring opening and decarboxylation to the halogenated tetra-... 

The Curtius Rearrangement is the thermal decomposition of carboxylic azides to produce an isocyanate. These intermediates may be isolated, or their corresponding reaction or hydrolysis products may be obtained. 

The thermal decomposition of terminal vinyl azides was originally believed to give only nitriles or, in some cases, indoles. The presence of 3-monosubstituted 1-azirines, however, has been inferred in the photolytic decomposition of some terminal azides.22,29 30 The nitrile is thought to arise in a similar manner to the ketenimine by an analogous Curtius-type rearrangement. The ketenimine (53) derived from terminal azides is unstable and rearranges to the nitrile (54). 

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