Aryloxenium ions 1 are reactive intermediates that are isoelectronic with the better known arylcarbenium and arylnitrenium ions. They are proposed to be involved in synthetically and industrially useful oxidation reactions of phenols. However, mechanistic studies of these intermediates are limited. Until recently, the lifetimes of these intermediates in solution and their reactivity patterns were unknown. Previously, the quinol esters 2 have been used to generate 1, which were indirectly detected by azide ion trapping to generate azide adducts 4 at the expense of quinols 3, during hydrolysis reactions in the dark. Laser flash photolysis (LFP) of 2b in the presence of O(2) in aqueous solution leads to two reactive intermediates with lambda(max) 360 and 460 nm, respectively, while in pure CH(3)CN only one species with lambda(max) 350 nm is produced. The intermediate with lambda(max) 460 nm was previously identified as 1b based on direct observation of its decomposition kinetics in the presence of N(3)(-), comparison to azide ion trapping results from the hydrolysis reactions, and photolysis reaction products (3b). The agreement between the calculated (B3LYP/6-31G(d)) and observed time-resolved resonance Raman (TR(3)) spectra of 1b further confirms its identity. The second intermediate with lambda(max) 360 nm (350 nm in CH(3)CN) has been characterized as the radical 5b, based on its photolytic generation in the less polar CH(3)CN and on isolated photolysis reaction products (6b and 7b). Only the radical intermediate 5b is generated by photolysis in CH(3)CN, so its UV-vis spectrum, reaction products, and decay kinetics can be investigated in this solvent without interference from 1b. In addition, the radical 5a was generated by LFP of 2a and was identified by comparison to a published UV-vis spectrum of authentic 5a obtained under similar conditions. The similarity of the UV-vis spectra of 5a and 5b, their reaction products, and the kinetics of their decay confirm the assigned structures. The lifetime of 1b in aqueous solution at room temperature is 170 ns. This intermediate decays with first-order kinetics. The radical intermediate 5b decomposes in a biphasic manner, with lifetimes of 12 and 75 mus. The decay processes of 5a and 5b were successfully modeled with a kinetic scheme that included reversible formation of a dimer. The scheme is similar to the kinetic models applied to describe the decay of other aryloxy radicals.

Abstract2-(4-Aminophenyl)benzothiazoles related to 1 are potentially important pharmaceuticals. Metabolism apparently involves oxidation and esterification to 3. In water, hydrolysis and photolysis of 3 generates the nitrenium ion 4 that can be detected indirectly by N 3 − trapping and directly by UV-vis spectroscopy following laser flash photolysis. The transient, with λ max 570 nm, and a lifetime of 530 ns, reacts with N 3 − at a diffusion-controlled rate and generates the quinol 6 by reaction with water.Benzothiazole derivatives such as 2-(4-aminophenyl)benzothiazole, 1, are under investigation as anti-tumor, antifungal, and antibacterial agents, 1-3 and as radiopharmaceuticals for binding and in vivo imaging of Aβ-plaques, one of the earliest pathological processes in the development of Alzheimer's disease. 4 One anti-tumor derivative of 1 is currently in Phase 1 clinical trials in Great Britain. 5 The use of 1 and its derivatives as anti-tumor agents requires biological activation. 5,6 The proposed metabolism of 1 to form the active agent 3 is shown in Scheme 1, although neither 2 nor 3 had been isolated and characterized. It is presumed that 3 further decomposes into a reactive electrophile, but no direct evidence for this proposal has been presented. 7 We have succeeded in synthesizing both 2 and 3 from 2-(4-nitrophenyl)benzothiazole using procedures we previously developed for making similar derivatives of carcinogenic aromatic amines (Scheme 2). 8 Reduction of the nitro compound 9 with hydrazine hydrate in the presence novakm@muohio.edu. † Miami University § The Ohio State University Supporting Information Available Experimental details, a Table of rate constants, Figure S1, synthesis of 2 and 3, NMR spectra of 2 and 3. This material is available free of charge via the internet at http://pubs.acs.org. of 5% Pd/C catalyst generates 2 in moderate yield, while tratment of 2 with acetyl cyanide in the presence of N-ethylmorpholine provides 3 in satisfactory yield. We now report the indirect and direct detection of nitrenium ion 4 (Scheme 3) from hydrolysis and photolysis of 3. NIH Public AccessKinetics of the decomposition of 3 (2.5 × 10 −5 M) at pH 7.1 in phosphate buffer, and the formation of the major hydrolysis product 6 (Scheme 3, identified by HPLC and 1 H NMR comparison to an authentic sample 10 ) monitored by UV spectroscopy, are described by two pseudo-first-order rate constants, k o and k 1 . HPLC studies ( Figure 1A) show that the larger rate constant, k o governs the decay of 3, while the appearance of 6 is biphasic, and is fit well by a rate equation for two consecutive first-order reactions. The larger rate constant generated by the fit is equivalent in magnitude to k o measured for the disappearance of 3. The rate of appearance of 6 is limited by the smaller rate constant, k 1 . Kinetics of the appearance of 6 are consistent with its formation from a long-lived intermediate (lifetime ca. 2 h at 10 °C) that is generated by hydrolysis of 3. Steady-state photolysis of an identical aqueous soluti...