Synthesis and Spin‐Trapping Properties of a Trifluoromethyl Analogue of DMPO: 5‐Methyl‐5‐trifluoromethyl‐1‐pyrroline N‐Oxide (5‐TFDMPO)1. Issue 14 (3rd March 2014)

• Record Type: Journal Article
• Authors: Karoui, Hakim; Nsanzumuhire, Céline; Le Moigne, François; Hardy, Micael; Siri, Didier; Derat, Etienne; Rockenbauer, Antal; Ouari, Olivier; Tordo, Paul
• Is Part Of: Chemistry. Volume 20:Issue 14(2014)
• Page Start: 4064
• Page End: 4071
• Publication Date: 2014-03-03
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201303774
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The 5‐diethoxyphosphonyl‐5‐methyl‐1‐pyrroline <italic>N</italic>‐oxide superoxide spin adduct (DEPMPOOOH) is much more persistent (about 15 times) than the 5, 5‐dimethyl‐1‐pyrroline <italic>N</italic>‐oxide superoxide spin adduct (DMPOOOH). The diethoxyphosphonyl group is bulkier than the methyl group and its electron‐withdrawing effect is much stronger. These two factors could play a role in explaining the different half‐lifetimes of DMPOOOH and DEPMPOOOH. The trifluoromethyl and the diethoxyphosphonyl groups show similar electron‐withdrawing effects but have different sizes. We have thus synthesized and studied 5‐methyl‐5‐trifluoromethyl‐1‐pyrroline <italic>N</italic>‐oxide (5‐TFDMPO), a new trifluoromethyl analogue of DMPO, to compare its spin‐trapping performance with those of DMPO and DEPMPO. 5‐TFDMPO was prepared in a five‐step sequence by means of the Zn/AcOH reductive cyclization of 5, 5, 5‐trifluoro‐4‐methyl‐4‐nitropentanal, and the geometry of the molecule was estimated by using DFT calculations. The spin‐trapping properties were investigated both in toluene and in aqueous buffer solutions for oxygen‐, sulfur‐, and carbon‐centered radicals. All the spin adducts exhibit slightly different fluorine hyperfine coupling constants, thereby suggesting a hindered rotation of the trifluoromethyl group, which was confirmed by variable‐temperature EPR studies and DFT calculations. In phosphate buffer at pH 7.4, the half‐life of 5‐TFDMPOOOH is about three times shorter than for DEPMPOOOH and five times longer than for DMPOOOH. Our results suggest that the stabilization of the superoxide adducts comes from a delicate balance between steric, electronic, and hydrogen‐bonding effects that involve the β group, the hydroperoxyl moiety, and the nitroxide.</p> </abstract>