Laser Flash Photolysis Studies on the First Superoxide Thermal Source. First Direct Measurements of the Rates of Solvent-Assisted 1,2-Hydrogen Atom Shifts and a Proposed New Mechanism for This Unusual Rearrangement¹

Abstract

The thermal decomposition of bis(4-carboxybenzyl)hyponitrite (SOTS-1) in aerated water under physiological conditions has previously been shown to give the superoxide radical anion in a yield of 40 mol % (Ingold, K. U.; et al. J. Am. Chem. Soc. 1997, 119, 12364). The absolute kinetics of the elementary reactions involved in the cascade of events leading from the first-formed water-soluble benzyloxyl radical to superoxide have been determined by laser flash photolysis. On the basis of these kinetics it is concluded that SOTS-1 will be suitable for studies of superoxide-induced oxidative stress in most biological systems. A water-assisted 1,2-H shift converting benzyloxyl into the benzyl ketyl radical is an important step in the above reaction cascade. The kinetics of the 1,2-H shift assisted by H 2 O, D 2 O, and a number of nucleophilic alcohols have been measured for the first time. These data have led to a proposed new mechanism involving the initial formation of a ketyl radical anion and an oxonium cation which generally collapse to give the neutral ketyl radical as the first observable product on the time scale of our experiments (ca. 80 ns).

Expedient Solution‐Phase Synthesis and NMR Studies of Arylopeptoids

“…[15] A suspension of finely ground potassium tert-butoxide (2.24 g, 20.0 mmol) in Et 2 O (200 mL) was added dropwise over 1.5 h at room temp. under N 2 to a solution of 4-(bromomethyl)benzoyl bromide (5.56 g, 20.0 mmol) in Et 2 O (150 mL).…”

“…NMR spectra were in full accordance with those reported in the literature. [15] tert-Butyl 3-(Bromomethyl)benzoate (m-1): Treatment of 3-(bromomethyl)benzoyl bromide (1.39 g, 5.00 mmol) by the same procedure as used in the synthesis of p-1 yielded m-1 (877 mg, 65 %) as a colorless solid. R f (heptane/EtOAc 99:1) = 0.05; m.p.…”

The Fenton Reaction in Aerated Aqueous Solutions Revisited

“…This suggests that either R 3 O · radicals are formed in these reactions, which might be true also for reaction (19), or that reaction (4c) takes place in these systems to produce another mixture of R · radicals than reaction (15). R 3 O · radicals might decompose via: [47] CHRЈRЈЈO · Ǟ fast · CRЈRЈЈOH (26) This is, for example, expected to happen for fatty acid hydroperoxides, which are formed biologically, or for the radical formed from (CH 3 ) 3 COOH via: (27) with k = 2.0 × 10 3 s -1 , [48] etc.…”

The frequently overlooked importance of solvent in free radical syntheses

“…Two of these unimolecular reactions have very much higher rates in water and alcohols than in non-polar solvents, while the third has lower rates in polar and H-bond donor (HBD) solvents than in non-polar solvents. These competing reactions are: (i) b-scission of the alkoxyl radical, XCR,R 0 O , with formation of the carbonyl compound, R,R 0 CQO; 20,21 (ii) primary (and secondary) alkoxyls can form ketyl radical anions (or ketyl radicals at low pH) via a 1,2-H-atom shift; [22][23][24] and (iii) isomerization involving a 1,2-shift of an aryl group from carbon to the O oxygen (i.e., an O-neophyl rearrangement), 25,26 see Scheme 3. As illustrated by the kinetic data given in Scheme 3 both b-scissions and 1,2-H shifts in alkoxyl radicals are very strongly accelerated by hydroxylic solvents compared with their rates in benzene or chlorobenzene.…”

“…In any particular solvent, both b-scissions and 1,2-H-atom shifts increase in rate as the product radical becomes more stable. For example, for the b-scission: PhC(O )MeR -PhC(QO)Me + R ; the rates of loss of R increase along the series: R = Me ,E t , i-Pr , t-Bu , PhCH 2 , while the estimated rate constant for the 1,2-H-atomshift for CH 3 24 The solvent-induced acceleration of b-scission is due to stronger solvation of the carbonyl product than of its precursor alkoxyl radical, particularly by HBD solvents. In sharp contrast, the O-neophyl rearrangements of alkoxyl radicals (1,2-aryl group shifts) are retarded by polar, 25 and particularly by HBD, 26 solvents because, for these unimolecular alkoxyl radical reactions it is the starting alkoxyl that is more strongly solvated than the product phenoxymethyl radical.…”