4447-54-5

Reported is a safe, rapid method for the synthesis of α-nitro esters via the trapping of nitronium ions. The two-stage nitration and subsequent deacetylation of readily available 1,3-dicarbonyl compounds was achieved using a biphasic semicontinuous approach. α-Nitro esters and amides were obtained in good overall yields (53-84%). Some of the α-nitro-1,3-dicarbonyl intermediates exhibit enhanced reactivity and undergo an acid-catalyzed Nef-type reaction to α-oxo-carbonyls.

The spin trapping behavior of five carbamoyl-substituted EMPO derivatives, 5-aminocarbonyl-5-methyl-pyrroline N-oxide (CAMPO (AMPO)), 5-aminocarbonyl-5-ethyl-pyrroline N-oxide (CAEPO), 5-aminocarbonyl-5-propyl-pyrroline N-oxide (CAPPO), 5-aminocarbonyl-5-n-butyl-pyrroline N-oxide (CABPO), and 5-aminocarbonyl-5-n-pentyl-pyrroline N-oxide (CAPtPO), toward different oxygen- and carbon-centered radicals is described, the stabilities of the superoxide adducts ranging from about 8 to 17 min.

The HOF·CH3CN complex, readily prepared by passing F 2 through aqueous acetonitrile, is an exceptionally efficient oxygen transfer agent. It is unique in its capacity to oxidize various azides into the corresponding nitro derivatives. This method requires short reactions times and room temperature or below, and the desired nitro compounds were usually isolated in very good yields. The respective nitroso derivatives are believed to be the intermediates in this reaction. Functional groups such as aromatic rings, ketones, nitriles, halides, alcohols, and esters are tolerated. Sulfides react with HOF·CH3CN usually at the same rate as azides. Amines and olefins, however, react faster, so they have to be protected first. Nitro derivatives with various oxygen isotopes can be made using the labeled H 18OF·CH3CN. In the case of chiral azides the stereochemistry around the nitrogen-bonded carbons is retained.

Free radicals are involved in the onset of many diseases, therefore the availability of adequate spin traps is crucial to the identification and localization of free radical formation in biological systems. In recent studies several hydrophilic compounds of 2-ethoxycarbonyl-2-methyl-pyrroline-N-oxide (EMPO) have been found to form rather stable Superoxide spin adducts with half-lives up to twenty minutes at physiological pH. This is a major improvement over DMPO (t1/2 = ca. 45 s), and even over DEPMPO (t1/2 = ca. 14 min), the best commercially available spin trap for the unambiguous detection of superoxide radicals. In order to allow the detection of superoxide and also other radicals in lipid environment a series of more lipophilic derivatives of EMPO was synthesized and their structure unambiguously characterized by 1H and 13C NMR spectroscopy. In this way, six different compounds with a n-butyl group in position 5 and either an ethoxy- (EBPO), propoxy- (PBPO), iso-propoxy- (iPBPO), butoxy- (BBPO), sec-butoxy- (sBBPO) or tert-butoxycarbonyl group (tBBPO) in position 5 of the pyrroline ring were obtained and fully analytically characterized (NMR, IR). The stability of the superoxide adducts of all investigated spin traps were comparable with EMPO (t1/2 = ca. 8 min), except for the two compounds bearing an additional methyl group in position 3 or 4 of the pyrroline ring, 5-butyl-5-ethoxycarbonyl-3-methyl-pyrroline-N-oxide (BEMPO-3) and 5-butyl-5-ethoxycarbonyl-4-methyl-pyrroline-N-oxide (BEMPO-4), of which the superoxide adducts were stable for more than 30 min. Spin adducts of other carbon- and oxygen-centered radicals were also investigated.