Heteroaryl nitrenes

Aryl and heteroaryl nitrene insertion processes have also been employed in the synthesis of heterocycles. The azide 459, for example, is converted on irradiation into the imidazole 460,383 and dihydro-10-thiaisoalloxazines are obtained in good yield on photoelimination of nitrogen from 6-(2-azido-phenylthio)uracils.384... 

Heteroaryl nitrenes can be produced by thermolysis and photolysis, however, the reaction pathways are fundamentally different [17]. Under thermolytic conditions, ring cleavage is obtained, however, photolytically... 

The tetrazole is very much less sensitive to photolysis than the azide, and for a number of such systems photochemical generation of the heteroaryl nitrene has failed. This problem is important in nucleotide and nucleic acid chemistry, where azidopurines and azidopyrimidines are, at first sight, attractive candidates for photogenerated reagents. The position of the azide-tetrazole isomerization equilibrium is solvent dependent, and it is not possible to specify under what conditions (or in what kinds of receptor site) useful levels of photogenerated aryl nitrene can be produced. In general, therefore, it may be safer to avoid such systems if reasonable alternatives exist. 

Formation of l-aryl-l//-azepines is rare and occurs only with those arylnitrenes made sufficiently electrophilic by an electron-withdrawing, e.g. CN, N02 or CF3, ortho or para substituent. Even so, these docile nitrenes attack only electron-enriched arenes (e.g. mesity-lene or Af,Af-dimethylaniline) and are of minor synthetic importance (B-73MI51600). More reactive are 7r-deficient heteroarylnitrenes, and moderate yields (15-40%) of 1-heteroaryl-l//-azepines, e.g. (228 R=4,6-dimethoxy-l,3,5-triazin-2-yl), may be obtained by the photodecomposition of 2-azido-4,6-dimethoxy-l,3,5-triazine in a variety of aromatic substrates (81BCJ301). Interestingly, intramolecular insertion of arylnitrenes into arenes is more common and has been used for the synthesis of fused azepines, e.g. the azepinoindoles (229) from o-azidodiphenylmethanes (81JCS(P1)1132). 

Base-induced ring-opening of pyrimidines, or nitrene formation (as in the pyrolysis of azido-pyrimidines) can give imidazoles (see CHEC-I). There are also a few examples of photochemical ring contraction. For example, 4-heteroaryl substituted 1,4- (or 3,4-)dihydropyrimidines give some imidazole products (Equation (76)) <83RTC364>. 

The chemistry of heteroaryl azides is complex and its careful consideration is beyond the scope of the present chapter. Smith s [21] 1984 review presents a thoughtful analysis of the then existing results for this class of compounds. Here we focus exclusively on the chemistry of 1,3,5-triazinyl azides because they illustrate an important issue in nitrene chemistry—the spin multiplicity of the ground state. 

The products from the thermolysis of anthranils bearing a heteroaryl residue at position 3 are less predictable. 3-(2-Pyridyl)anthranils in boiling trichlorobenzene yield pyrido[l,2-h]cinnolin-6-iums (e.g., 139) (cyclization of the initially formed nitrene taking place only at the electron-rich nitrogen center) and no rearranged products.191 In contrast, the 3-(2-imidazolyl)-anthranil 108 (X = N, Y = CH) yields a mixture of the nitrene-induced rearrangement product (157) (63%) and the nitrene insertion product (158) (3%).131 The 3-(5-pyrazolyl)anthranil 108 (X = CH, Y = N) behaves similarly. 

Radical Reactions.—Thiazolyl, pyridyl, and other heteroaryl radicals formed by aprotic diazotization of the corresponding heterocyclic amines substitute homolytically on thiophen with the formation of 2-heteroaryl-thiophens as the main products in 20—50% yield. The results of competitive experiments indicate that the reactivity of thiophen in this reaction at 70—80 °C is slightly higher than that of benzene. The currently accepted mechanism of the decomposition of benzoyl peroxide in thiophen has been criticized on the basis of new experimental results. No free thienyl radicals are involved in the reaction, as demonstrated by scavenging experiments, and the bithienyls formed are probably derived from dimerization of a benzoyloxythiophen radical a-complex, with subsequent loss of benzoic acid. Nitrene insertion into the thiophen ring has been observed in the thermal decomposition of 2-(2-azidobenzyl)thiophen and similar compounds, leading to thieno[3,2-6]quinoline derivatives. ... 

Schuster, G. B. and Platz, M., Photochemistry of phenyl azide, Adv. Phototochem., 17, 69,1992. Smith, P. A. S., Aryl and heteroaryl azides and nitrenes, in Azides and Nitrenes, Reactivity and Utility, Scriven, E. E, Ed., Academic Press, Orlando, FL, 1984. 

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