Photolysis Of Aryl Azides Research Articles

Formation of 1,2,4-oxadiazoles in the course of photooxidation of aromatic azides in acetonitrile

Photolysis of aryl azides at room temperature in acetonitrile in the presence of oxygen proceeds as arene ring opening and acetonitrile trapping to afford 5-methyl-3-(5-oxopenta-1,3-dien-1-yl)-1,2,4-oxadiazoles. In the case of 4-methoxyphenyl azide, a product depriving of acetonitrile reactant, 1-hydroxyimino-3-methylcyclopentadiene-2-carbaldehyde, is also formed.

ChemInform Abstract: Photochemistry of ortho-Phenoxymethyl-Substituted Aryl Azides: A Novel Nitrene Rearrangement En Route to Isolable Iminoquinone Methides?

The answer to the question in the title is: probably yes. A surprising reaction is observed upon photolysis of aryl azide 1 in the presence of diethylamine. The iminoquinone methide 2 is isolable and is probably formed by a shift of the phenoxy group to the nitrene center followed by nucleophilic attack of diethylamine and elimination of phenol.

Two-Component Mixed and Patterned Films on Carbon Surfaces through the Photografting of Arylazides

Organic films have been grafted to glassy carbon surfaces by the photolysis of arylazides. Atomic force microscopy and electrochemical measurements reveal that the films are loosely packed. The methodology was expanded to prepare two-component thin films incorporating either a reactive tether species and a nonreactive background film or two different reactive tethers. Strategies were developed to generate both continuous mixed films and surfaces presenting patterns of two components. For patterning, the arylazide derivative was grafted onto previously modified glassy carbon surfaces. In this case, the first modification step is not limited to photografting, which increases the scope of the methods. For all grafted surfaces, the reactivity of tether species was confirmed by coupling electroactive targets to the tethers, followed by electrochemical monitoring. The ease of preparing surfaces with spatially controlled functionality offers promise for the design of sensing platforms on graphitic carbon substrates.

1H NMR aided elucidation of products derived from photodegradation of ethyl 3-azido-4,6-difluorobenzoate in 2,2,2-trifluoroethanol

The major products formed upon photolysis of ethyl 3-azido-4,6-difluorobenzoate in 2,2,2-trifluoroethanol- d 3 has been elucidated by 1H NMR analysis of the product mixture. Among the products formed and structurally elucidated was a hitherto unreported product formed during photolysis of aryl azides, namely azoxybenzene 19. The structural assignments of the major components of the reaction mixture were aided by comparison with 1H NMR data from synthetic reference materials and compound isolation. MS, MS/MS, and HPLC analysis as well as UV spectroscopy was also employed in order to confirm and aid the structural analysis.

Determination of Solvent‐Trapped Products Obtained by Photolysis of Aryl Azides in 2,2,2‐Trifluoroethanol

A series of nonfluorinated and fluorinated aryl azides with varied functionality patterns were irradiated in 2,2,2-trifluoroethanol with either a high-pressure or a low-pressure mercury lamp. Interestingly, one of the major products in these reactions was the result of the recombination of anilino and alkyl radicals to form the corresponding hemiaminal compounds. The structure of the recombination products was assigned unambiguously after proton/deuterium exchange experiments followed by MS and MS/MS analysis.

New syntheses of DNA adducts from methylated anilines present in tobacco smoke.

A new synthetic pathway for the formation of deoxyguanosine-monoarylamine adducts is described, involving the generation and use of arylnitrenes as electrophilic synthons. Photolysis of aryl azides, the most common method for generating arylnitrenes, was tested in the presence of 2'-deoxyguanosine. N-(2'-Deoxyguanosin-8-yl)monoarylamine (dG-C8-Ar) adducts were obtained, but the yields were typically low. Deoxygenation of nitro- and nitrosoarenes by triethyl phosphite in the presence of 2'-deoxyguanosine proved to be an effective method, by which dG-C8-Ar, (2'-deoxyguanosin-N1-yl)monoarylamine (dG-N1-Ar), and (2'-deoxyguanosin-O(6)-yl)monoarylamine (dG-O(6)-Ar) adducts were obtained in acceptable yields.

Photochemistry ofortho-Phenoxymethyl-Substituted Aryl Azides: A Novel Nitrene Rearrangement En Route to Isolable Iminoquinone Methides?

The answer to the question in the title is: probably yes. A surprising reaction is observed upon photolysis of aryl azide 1 in the presence of diethylamine. The iminoquinone methide 2 is isolable and is probably formed by a shift of the phenoxy group to the nitrene center followed by nucleophilic attack of diethylamine and elimination of phenol.

Reactivity and genotoxicity of arylnitrenium ions in bacterial and mammalian cells

Electrophilic arylnitrenium ions are considered to be the ultimate reactive intermediates formed by metabolism of mutagenic and carcinogenic arylamines and nitroarenes; they can produce DNA damage by reaction with specific sites on DNA bases. We studied their formation, reactivity and the genotoxic sequelae of their reactions with cellular DNA to understand the mutagenic and carcinogenic activities of arylamines and nitroarenes as a function of their chemical structure. Arylnitrenium ions were generated by the convenient non-metabolic procedure, photolysis of arylazides, to study the reactivity of these ultimate intermediates with DNA, by means of 32P-postlabelling, and the induction of histidine reversions in Salmonella, HPRT mutations and sister chromatid exchange in mammalian (Chinese hamster V79) cells. Good correlations were observed between the DNA-binding potencies and the mutagenic and SCE-inducing potencies of the arylnitrenium ions, among these the nitrenium ions derived from the heterocyclic food mutagens/ carcinogens MeIQ, IQ, and MeIQx. This suggests that the reactivity of the arylnitrenium ions and the quantity of adducts formed with DNA are the principal determinants of the final quantity of genetic alterations in Salmonella and in V79 cells. Conversely, the quality of the adducts, that is, the structure of the arylamine residue bound, appears to be of less significance.

Quantitative structure-activity relationships of mutagenic aromatic and heteroaromatic azides and amines.

Photolysis of arylazides with long-wavelength UV light in an aqueous medium produces short-lived reactive species that bind to DNA and induce mutations in Salmonella typhimurium TA98. Nitrenes are known reactive products of azide photolysis, so that the DNA-binding and mutagenic species is either a nitrene or nitrene derivative. In the present study we presupposed that the nitrenium ion is the key intermediate. The electronic properties of 19 nitrenium ions with different chemical structures were calculated by the semi-empirical method AM1 and the resulting values plotted against the logarithm of the mutagenicity (log MUT) by means of linear regression analysis. Log MUT correlates with the stability of the nitrenium ion, the energy level of the LUMO and the charges on the exocyclic nitrogen with r = -0.804, 0.865 and -0.874 respectively. Thus, the mutagenicity of the azides is directly proportional to the stability of the nitrenium ions and inversely proportional to the electrophilicity of the exocyclic nitrogen. Furthermore, the mutagenicity of the azides correlates with the mutagenicity of the corresponding arylamines with r = 0.91 (n = 13). These correlations support the key role of the nitrenium ions and demonstrate the value of their electronic structure for the prediction of the mutagenicity of arylazides and arylamines.

A novel pathway to the ultimate mutagens of aromatic amino and nitro compounds.

Photolysis of arylazides in aqueous media was recently found to generate presumed nitrenium ions, species which are generally considered as the ultimate mutagens/carcinogens derived from arylamines and nitroarenes. The primary photolysis products of arylazides, the arylnitrenes, can possibly react as electrophiles themselves, or they can be protonated and thus form the electrophilic nitrenium ions. Numerous arylazides and aryldiazides can be photoactivated to short-lived mutagens detectable in Salmonella typhimurium TA98. Structure-activity comparisons between arylazides and the matching arylamines and nitroarenes show correlations; e.g., phenyl azide and methyl-substituted phenyl azides are not mutagenic or only weakly mutagenic like aniline, nitrobenzene, and their methyl homologues, whereas 4-azidodiphenyl, 2-azidofluorene, 1-azidopyrene, azido-IQ, and azido-isoIQ are increasingly mutagenic in that order, like the matching amino and nitro compounds. It is hypothesized on the basis of these data that the nitrene/nitrenium ion is the reactive intermediate common to the three mutagenic pathways and that the reaction of the nitrene/nitrenium ion with DNA is rate limiting for the overall mutagenic process in Salmonella. The photochemical generation from arylazides of the reactive species, the nitrene/nitrenium ions, opens new perspectives for the understanding of the genotoxic activity of arylamines and nitroarenes in general and, specifically, of the food mutagens/carcinogens of the IQ type.

Photolysis of arylazides and generation of highly electrophilic DNA-binding and mutagenic intermediates.

Photolysis of arylazides with long wavelength ultraviolet (NUV) light in an aqueous medium produces short-lived reactive chemical species which bind to DNA and deoxynucleoside 3'-phosphates and induce reversion mutations in frameshift tester strains of Salmonella typhimurium. Nitrenes are known reactive products of azide photolysis, so the DNA-binding and mutagenic species is either a nitrene or a nitrene-derivative. An N-hydroxyarylamine intermediate, potentially formed from a nitrene and water, can be excluded because the mutagenic potencies of the reactive species in TA98 and in the hydroxylamine-resistant TA98/1,8-DNP6 are of the same order, and because the life-time of this species is very short. The mutagenic potency of the arylazide photolysis products decreases in the order azido-IQ greater than 1-azidopyrene greater than azido-MeIQx greater than 6-azidochrysene greater than 2-azidofluorene greater than 4-azidobiphenyl greater than 2-azido-naphthalene greater than 1-azido-naphthalene. This potency sequence correlates with that of the corresponding arylamines. Furthermore, their DNA binding products are chromatographically identical with those obtained in cellular, metabolizing systems from nitroarenes and arylamines. Therefore, the reactive, electrophilic azide photolysis product is very likely a nitrenium ion formed by protonation of a nitrene. Nitrenium ions are also the ultimate mutagens/carcinogens formed from nitroarenes and arylamines. Arylazides can therefore be considered as stabilized forms of arylnitrenium ions. The arylazide-nitrene technique reported here is new and simple and provides ready access to presumed nitrenium ions which are otherwise difficult to obtain.

Synthesis of 2-azido-3-methylimidazo[4,5-f]quinoline and photolytic generation of a highly reactive and mutagenic IQ derivative.

Azido-IQ (2-azido-3-methylimidazo[4,5-f]quinoline), a novel analog of the food mutagen and carcinogen IQ (2-amino-3-methylimidazo[4,5-f]quinoline) was synthesized and characterized. Both thermolysis and photolysis of this azide yield a short-lived nitrene which can react as an electrophile either directly or via protonation to a nitrenium ion. Reaction of the nitrene/nitrenium ion with water produces N-hydroxy-IQ; reactions with nucleotides and with DNA (in vitro and in cells) produce adducts efficiently. Correspondingly, high frequencies of mutations are induced in Salmonella typhimurium by photolyzed azido-IQ. Comparative mutation assays with the S. typhimurium strains TA98 and the hydroxylamine-resistant TA98/1,8-DNP6 provide evidence for a novel mechanism of mutation, direct reaction of the nitrene or nitrene-derived nitrenium ion with DNA without involvement of the hydroxylamine. The photolysis of arylazides promises to be a very convenient and generally applicable non-enzymatic procedure for the cell-free or intracellular generation of short-lived and highly reactive electrophilic species which are assumed to be identical with the metabolically formed ultimate mutagens/carcinogens of arylamines and nitroarenes.

Reaction of triplet aryl nitrenes and azides with molecular oxygen

Photolysis of aryl azides in the presence of oxygen gives nitro-compounds via a triplet nitrene and, in the case of para-substituted azides, also the azoxy-compound, probably via the nitroso-compound from the reaction of excited azide with oxygen, while triethyl phosphite deoxygenation of nitrosobenzene under oxygen also gave some nitrobenzene.