Radical-nucleophilic substitution (SRN1) reactions: electron spin resonance studies of electron capture processes. Part 6. Nitroimidazole derivatives

Abstract

Exposure of dilute solutions of a range of nitroimidazole derivatives [(1)–(5), (8)–(12), and (14)] in methanol (CD₃OD) or methyltetrahydrofuran to ⁶⁰Co γ-rays at 77 K gave the corresponding radical anions, detected by e.s.r. spectroscopy. Analysis of the results shows that the radical anions of 4- and 5-nitroimidazoles [(8) and (9), and (1)–(5), respectively] have remarkably similar SOMOs, with ca. 46% of the SOMO localised on the nitrogen atom of the nitro group and ca. 20% on the adjacent CH units. Spin densities on the two ring nitrogen atoms and on C-2 are low. In contrast, the spin density on the nitro nitrogen of the radical anions of the 2-nitroimidazoles (12) and (13) is only ca. 34%, and is very low at both methine sites.

For the 4-nitro derivatives, when the N(1)-substituent was –C(Me)₂NO₂, the radical Me₂ĊNO₂ was a major product. When the N(1)-substituent was p-nitrobenzyl, electron capture occurred preferentially at the aryl ring.

For the 2-bromomethyl-5-nitro derivative (2) dissociative electron capture occurred as a major pathway, and, in this case, a small hyperfine coupling to the bromine nucleus was detected for the radical anion. When the C(2)-substituent was CH₂Cl, CH₂OH, or CH₂NMe₃[(1), (2), or (4)], only the parent radical anion was observed: there was no loss of Cl^–, ^–OH, or NMe₃, respectively. The significance of these, and related liquid-phase data, is discussed in terms of S_RN1 reactions observed for some of these compounds. The results are also discussed in terms of the large differences in antimicrobial activity of 2-, 4-, and 5-nitro derivatives.