N-Oxides s. a. Nitrones

Recendy, PEN, a-4-pyridyl-oxide-N-t-butyl nitrone (POEN) or 5-5,dimethyl-1, pyrroline-N-oxide (DMPO) were evaluated in models of experimental shock (endo-toxic, traumatic and mesenteric artery occlusion in rats). All three nitrones, when given prior to the insult intraperitoneally, were protective. When the nitrone s spin trapping ability was inactivated by exposure to solar light and air, they were no longer efficacious (Novelli, 1992). 

A strictly dehned region of chemical shifts of C2, C4, and C5 atoms in A-oxides of 4A-imidazoles allows to dehne clearly the position of the A-oxide oxygen atom (102). Chemical shifts of the a-C nitrone group in a-N-, O-, and S-substituted nitrones are located in the region of 137 to 150 ppm (388, 413). On the basis of 13C NMR analysis of 3-imidazoline-3-oxide derivatives, the position of tautomeric equilibria in amino-, hydroxy-, and mercapto- nitrones has been estimated. It is shown that tautomeric equilibria in OH- and SH-derivatives are shifted toward the oxo and thioxo forms (approximately 95%), while amino derivatives remain as amino nitrones (413). In the compounds with an intracyclic amino group, an aminonitrone (A) - A-hydroxyaminoimino (B) tautomeric equilibrium was observed (Scheme 2.76), depending on both, the nature of the solvent and the character of the substituent in position 2 of the heterocycle (414). 

For the alkynyUiydroxylamines 274 smdied by Holmes (309,311), initial intramolecular 1,3-azaprotiocyclotransfer affords the N-oxides 275 via a 5- or a 6-exo-dig process [Baldwin s terminology (312)], which then tautomerize to the cyclic nitrones (276) (Scheme 1.57). The 1-exo-dig cyclization required for the formation of a seven-membered nitrone (277) by this approach from 278 was found to be disfavored with respect to the alternative reaction of hydroxylamine and alkene 5-exo-trig process) to afford a mixture of the alkynylpyiTolidines 279... 

Dipolar cycloadditions of pyrroHne N-oxides, which could be regarded as cycHc nitrones , on electron-poor aUcenes, represent a viable method to obtain highly substituted pyrrolizidines. Enantiopure (S)-3-alkoxypyrroline N-oxide (170), on the other hand, has been exploited in stereoselective cycloaddition reactions with solid-supported unsaturated esters (169) [266]. A both regio- and stereoselective cycloaddition took place in this case, affording the desired compound (171) as a single isomer (Scheme 36). 

B-adducts involve the -carbon atom endo/exo notation, as usual, defines the di-astereoisomeric relation of the C-N-0 nitrone-group with respect to the substi-tuent(s). The isomer definition is made clearer in the transition structures which are taken to be "concerted according to the extant literature. One can see that all the adducts allowed are present in the reaction mixture with variable, but non negligible fractions. The same is true for the reactions of 3,4-dihydro-isoquinoline-N-oxide and C-phenyl-N-methylnitrone,3 whereas the reactions of N-H-nitrone (H-nitrone), N-Me-nitrone and N-(t)-Bu-nitrone3t>.c lead to a single adduct, which, in our notation, is the B-regioadduct (Scheme 3). The experimental trends extracted from Tables 1-2 and from the cited literature can be summarised as follows ... 

A soln. of startg. hydroxamic acid in dichloromethane treated with a 20% molar excess of methyl triflate at room temp, for 48 h - intermediate nitrone hydrotriflate (Y 95%), in deuteriochloroform deprotonated with a 20% molar excess of triethylamine methyl N-(l,l-dimethylethyl)-benzenecarboximidate N-oxide (Y 85% overall). The products are relatively unstable, being converted to 1-functionalized nitrones with a variety of nucleophiles. F.e., also with ethyl triflate, and deprotonation on silica gel or with the weakly basic anion exchange resin. Bio-rad AG3-X4, s. J.A. Warshaw et al., J. Org. Chem. 54, 1736-43 (1989). 

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