- Spin adducts of several N-2-(2-alkoxycarbonyl-propyl)-α- pyridylnitrone derivatives with superoxide, alkyl and lipid-derived radicals
-
Several derivatives of N-t-butyl-α-phenylnitrone (PBN) such as N-2-(2-ethoxycarbonyl-propyl)-α-phenylnitrone (EPPN) have recently been reported to form superoxide spin adducts (t1/2 ca. 2-7 min at pH 7.0), which are considerably more stable than their respective PBN or DMPO adducts (t1/2 ca. 10 and 45 s, respectively). In continuation of our studies on structure optimization of EPPN derivatives, a series of 12 novel spin traps with 2-, 3- and 4-pyridinyl substituents was synthesized and fully characterized by 1H NMR, 13C NMR and IR spectroscopy. In addition to the replacement of the phenyl ring by a 2-, 3- or 4-pyridinyl substituent, the ethoxy group of the parent compound EPPN was replaced by either a propoxy, iso-propoxy, or cyclopropylmethoxy moiety. Superoxide adducts of all PPyN derivatives were considerably more stable than those of the respective EPPN derivatives with half-lives ranging from about 6 to 11 min. In addition, alkoxyl radical adducts were also considerably more stable than those of the EPPN series. Hydroxyl radical adducts were not detected, on the other hand, very stable spin adducts were formed from a series of carbon centered radicals, e.g. from the methyl or hydroxymethyl radical. The novel spin traps are offering an alternative to PBN or POBN, especially where the higher stability of oxygen-centered radical adducts is of major importance. All of them can easily be synthesized from commercially available compounds in two or three steps.
- Stolze, Klaus,Udilova, Natascha,Rosenau, Thomas,Hofinger, Andreas,Nohl, Hans
-
-
Read Online
- Synthesis of a polar phosphinoferrocene amidosulfonate ligand and its application in pd-catalyzed cross-coupling reactions of aromatic boronic acids and acyl chlorides in an aqueous medium
-
The reaction of [1′-(diphenylphosphino)ferrocenyl]methylamine (1), generated in situ from its hydrochloride and triethylamine, with 2-sulfobenzoic anhydride afforded an anionic phosphino-amide, which was isolated as a triethylammonium salt, Ph2PfcCH2NHCOC6H4SO3(HNEt3) (2; fc = ferrocene-1,1′-diyl). A similar reaction of 1 with phthalic anhydride only furnished the salt (Ph2PfcCH2NH3)[C6H4CO2H(CO2)]. When it was reacted with [PdCl2(MeCN)2] and [LNCPd(μ-Cl)]2 (LNC = 2-[(dimethylamino-κN)methyl]phenyl-κC1), compound 2 gave rise to the bis-phosphine complex [PdCl2(2-κP)2] and the bridge-cleavage product [LNCPdCl(2-κP)], respectively. An analogue of the latter complex containing 2′-amino-[1,1′-biphenyl]-2-yl-κ2N,C2 as the auxiliary chelating ligand, compound 8, was prepared in a similar manner from 2 and the respective Pd precursor. Finally, the reaction of 2 with [LNCPd(acac)] proceeded with the replacement of the acetylacetonate ligand (acac), affording a dipalladium complex featuring two phosphinosulfonate anions as the O,P-bridges, [LNCPd(μ(P,O)-Ph2PfcCH2NHCOC6H4SO3)]2, which was structurally characterized by single-crystal X-ray diffraction analysis. All of these Pd(II) complexes, especially compound 8, formed active catalysts for Pd-mediated cross-coupling of aromatic boronic acids with benzoyl chlorides to produce substituted benzophenones in toluene (benzene)-water biphasic mixtures. This particular coupling reaction was employed during the preparation of 4′-chloro-4-hydroxybenzophenone, which was in turn converted to fenofibrate, a generic drug widely used to reduce cholesterol levels in blood.
- ?koch, Karel,Císa?ová, Ivana,?těpni?ka, Petr
-
supporting information
p. 3378 - 3387
(2016/10/21)
-
- Spin trapping of superoxide, alkyl- and lipid-derived radicals with derivatives of the spin trap EPPN
-
The N-t-butyl-α-phenylnitrone derivative N-2-(2-ethoxycarbonyl-propyl)-α-phenylnitrone (EPPN) has recently been reported to form a superoxide spin adduct (t1/2=5.25min at pH 7.0), which is considerably more stable than the respective N-t-butyl-α -phenylnitrone or 5,5-dimethylpyrroline N-oxide adducts (t1/2 ～10 and 45s, respectively). In continuation of our previous studies on structure optimization of 5-(ethoxycarbonyl)-5-methyl-1-pyrroline N-oxide derivatives, a series of six different EPPN derivatives was synthesized and characterized by 1H NMR, 13C NMR and IR spectroscopy. The ethoxy group of EPPN was replaced by a propoxy, iso-propoxy, n-butoxy, sec-butoxy, and tert-butoxy moiety, as well as the phenyl by a pyridyl ring. Electron spin resonance spectra and stabilities of the superoxide adducts of the propoxy derivatives were found to be similar to those of the respective EPPN adduct, whereas the electron spin resonance spectra of the superoxide adducts of N-2-(2-ethoxycarbonyl-propyl)-α-(4-pyridyl) nitrone and the butoxy derivatives were accompanied by decomposition products. In contrast to the 5-(ethoxycarbonyl)-5-methyl-1-pyrroline N-oxide series, no significant improvement of the superoxide adduct stability could be obtained when the ethoxy group was replaced by other substituents. Carbon centered radical adducts derived from methanol, ethanol, formic acid and linoleic acid hydroperoxide were more stable than those of 5,5-dimethylpyrroline N-oxide, whereas among the alkoxyl radicals only the methoxyl radical adduct could be detected.
- Stolze, Klaus,Udilova, Natascha,Rosenau, Thomas,Hofinger, Andreas,Nohl, Hans
-
p. 1717 - 1726
(2007/10/03)
-
