Azido compounds stability

When thermolyzing azido compounds, the question arises as to whether an observed rearrangement is achieved in one step, concerted to the elimination of Nj, or whether there are two steps, elimination and rearrangement, with nitrenes as intermediates. Generally, thermolysis of azidoboranes is more probably a concerted process (22). The decomposition of (tPr2N)2BN3, however, carried out at 450°C, gives a product, besides the main product of Eq. (19), that has to be interpreted in terms of a nitrene stabilized by an intramolecular CH insertion [Eq. (19b)]. 

Azido compounds are versatile molecules. They are used extensively in both organic reactions and chemical biology. All azides are potentially explosive and must be handled with care. Azides, which have been known for over 100 years, are the most widely used precursors of nitrenes. like diazo compounds, they possess a linear 1,3-dipolar stracture and are easily prepared, often by introduction of the azide (Nj ) ion from inorganic salts such as sodium azide. The thermal stability of azides is critically dependent on the substituent on nitrogen. Most azides decompose thermally in the range 100-200 °C to give nitrenes. Azides are also readily decomposed photochemically, and this is often the method of choice, particularly for mechanistic studies. Like diazo compounds, the decomposition of... 

Several simple derivatives of azetine are known, although most of these bear substituents that help stabilize the compound by extending the conjugation of the endocyclic double bond. For example, 2-phenylazetine is obtained by the thermolysis of 1-azido-l-phenylcyclopropane nitrogen is lost from the azide group and a nitrene may be formed, prior to ring expansion (Scheme 8.2). 

An acyclic azide structure was rejected since the compounds show no azide IR absorption. A less likely three-membered ring was also considered. Comparison with other potential dihydro-SIV-thiatriazoles was made. Simple a-azido thioethers show the spectroscopic and chemical properties of azides rather than of dihydro-Slv-thiatriazoles. o-(Methylthio)phenyl azide was prepared but also showed the characteristics of an azide.70 These results cast doubt on the suggested structure, since the only essential difference in composition is an amino group that is not in a position to stabilize the suggested heterocyclic ring. Structure R1(R3R4N)C=N—N=N—SR2 is an alternative, but. further consideration must await X-ray crystallographic analysis. 

Careful and small-scale handling of organic azides, which are usually heat- or shock-sensitive compounds of varying degrees of stability, is necessary. The presence of more than one azido group, particularly if on the same atom (C or N) greatly reduces stability. 

The 2 -azido group of cytarazid renders the nucleoside more resistant to deamination to the 2 -azidouridine derivative (153) by deoxycytidine deaminase, but was also observed to reduce substrate affinity for the deoxycytidine kinase necessary for anabolic phosphorylation to the active cytarazid 5 -triphosphate [180]. Conversely, cytarazid was a more potent inhibitor of the target DNA polymerases a and K = 0.6 and 0.7 //M, respectively) than the parent ara-C (.A = 10 and 17 fiM, respectively), and the dissimilar spectrum of antitumour activity exhibited by the two compounds was attributed to differences in stability, metabolic activation and inhibitory potency [180, 181]. Interestingly, the instability of cytarazid to thiols present in the assay media, was commented on but not pursued [180]. In view of previous discussions concerning the bioreduction of AZT... 

The 3-azido- 1,2,4-triazoles (230) exist in the azide form rather than the triazolotetrazole form.481-484 These compounds were obtained by cyclization of the hydrazonyl bromides (229, R = H) and by treating the 3-hydrazinotriazole (233) with nitrous acid482 (Scheme 26). The former reaction involves a preferential ring interconversion of tetrazole to triazble and presumably could be included in the general classification of Eq. (37) An alkyl substituent located in the tetrazole moiety appears to have a stabilizing influence on the triazolotetrazole ring system, since the bicyclic compounds (232), not azides (231), were obtained when the... 

The tetrazole form is favored in the solid state and in basic solution, and the azido form predominates in acidic solution.579 The presence of the phenyl group adjacent to the tetrazole ring is reported to stabilize the tetrazole form.579 When these compounds contain a second azidoazomethine moiety, e.g., 313, one of the azide groups remains in the open-chain form, and in solution mixtures of isomers are... 

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