Intramolecular 1,3-Dipolar Cycloaddition of Alkenylnitrones of the 4H-Imidazole Series: Synthesis of a New Nitroxide pH-Sensitive Spin Probe

Abstract

A new method was used for the preparation of a pH-sensitive spin probe involving an intramolecular 1,3-dipolar cycloaddition - reductive isoxazolidine ring-opening - oxidation reaction sequence. 2-(2-Allyloxyphenyl)-5-R-4,4-dimethyl-4H-imidazole-3-oxides (R = Me, NMe₂), prepared from 3-hydroxylamino-3-methylbutan-2-one, undergo intramolecular 1,3-dipolar cycloaddition upon heating in toluene. Treatment of the cycloadducts with low-valence titanium (LVT) reagent resulted in reductive cleavage of the N-O bond of the isoxazolidine ring to give 3′-hydroxymethyl-5,5-dimethyl-4-R-2,5-dihydrospiro[imidazol-2,4′-chromane]s. The amine (R = NMe₂) was then oxidized with MCPBA to the target nitroxide - 3′-hydroxymethyl-5,5-dimethyl-4-dimethylamino-2,5-dihydrospiro[imidazole-2,4′-chroman]-1-oxyl.

Key words

1,3-dipolar cycloaddition - low-valence titanium - nitroxide radical - 4H-imidazole 3-oxide - pH-sensitive spin probe

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