Photochemistry of 2-Azido-1-methylimidazole in Aqueous Solutions. Observation of the 1-Methyl-2-imidazolylnitrenium Ion

Abstract

Irradiation of 2-azido-1-methylimidazole (12) in aqueous solution gives products from two reaction channels. One pathway involves a ring opening typical of azidoheterocycles. The observed products are glyoxal bis-hydrate, the methylammonium ion, and cyanamide; a glyoxal bis-oxime is presumed to be the intermediate initially formed in the ring opening. The other pathway leads to products that retain the five-membered ring, the 2-amino-4,5-dihydro-4,5-dihydroxy-1-methylimidazolium ion 3, its monophosphate ester 6 when the irradiation is carried out in phosphate buffer, and glutathione adducts 7 and 8 when glutathione (GSH) is present. These products have been previously observed in the reactions of 2-hydroxylamino-1-methylimidazole in aqueous solution, and arise from reaction of the 1-methyl-2-imidazolylnitrenium ion (2 + ) with water, phosphate, and GSH. This pathway is therefore proposed to involve formation of the cation 2 + via protonation of the singlet 1-methyl-2-imidazolylnitrene 13 formed upon irradiation of the azide. A single transient species undergoing exponential decay with λmax at 230−235 nm is observed with flash photolysis. This transient is assigned to 2 + on the basis of the pH dependence of the yields of products, and especially because of the correspondence of k 2(GS-):k s ratios measured directly with flash photolysis and by competition kinetics starting from the hydroxylaminoimidazole. The cation 2 + has a lifetime in water of 100 ms, and shows a high selectivity for GSH with k 2(GS-) = 3 × 107 M-1 s-1. There is evidence that this class of nitrenium ion is formed upon reductive metabolism of 2-nitroimidazoles. Thus this class of drugs is capable of producing a relatively long-lived electrophile in biological systems.

Aryl Nitrenium Ions in Aqueous Solution

“…McClelland and coworkers examined the hydrolysis of 94. [141][142][143][144] The hydrolysis mechanism of Scheme 4.28 is consistent with kinetic data. 141,142 An intermediate that can be trapped by H 2 O, 142 phosphate, 143 or glutathione (GSH) 139,142 was identified as the nitrenium ion 95.…”

“…produced by protonation of nitrene 96a generated by LFP of azide 97a. 144 The rate constants k s and k gs-were determined to be 9.4 s À1 and 3 Â 10 7 M À1 s À1 , respectively. 144 The ion 95a has a lifetime of over 100 ms at neutral pH in the absence of buffers or other nucleophiles.…”

Photochemical Reactivity of 2‐Azido‐1,3‐thiazole and 2‐Azido‐1,3‐benzothiazole: A Procedure for the Aziridination of Enol Ethers

“…[2] Among these compounds, 3 does not isomerize, [3] and it undergoes photochemical ring cleavage [4] that provides a facile route to small molecules such as heterodienes, which are useful buildingblocks in hetero-Diels-Alder reactions. [5] These studies indicated that the azido-tetrazole equilibrium is normally affected by the solvent and temperature.…”

“…[6] In light of these results, we would expected that the photochemical reactivity of azido-tetrazole mixtures 1 and 2 does not differ substantially from the photochemical behaviour of azide 3, even if this latter was carried out in water. [4] This study was carried out in view of the chemical, [7] biological [8] and pharmacological [9] importance of these nitrogen-linked azole systems and to find the influence on the photochemical reactivity of the cyclized or open-chain forms.…”

Photochemical Arylation of Brønsted Acids with 2‐Azidobenzimidazole

“…McClelland and co-workers proposed a similar ring opening for the nitrene derived from 2-azido-1-methylimidazole in aqueous solution. [9] Pozharskii and coworkers have shown that oxidation of 1,2-diaminobenzimidazole leads to the corresponding coarctate ring opening after oxidation, affording 3-amino-1,2,4-triazines through re-cyclization. [10] Proton shift at 17 to the more basic nitrogen affords intermediate 18.…”