1-Pyrroline 1-oxide, 5,5-dimethyl

The same rearrangement was observed somewhat later by the irradiation of 5,5-dimethyl-A -pyrroline oxide (13)/ The product (11% yield) was shown to be identical with the oxazirane (14) synthesized from 5,5-dimethyl-A -pyrroline and hydrogen peroxide. 

Pyrrole oxidizes in air to red or black pigments of uncertain composition. More usehil is the preparation of 2-oxo-A -pyrrolines, which is best carried out by oxidation of the appropriate pyrrole with in pyridine (37), eg, 3,5-dimethyl-ethyl-3-pyrrolin-2-one [4030-24-4] from... 

By means of perbenzoic acid oxidation, a bicyclic oxazirane (233,234) (152) is formed from 5,5-dimethyl-4-phenyl-/l -pyrroline (151). 

The dimer of 1-methyl- -pyrroline (39) was obtained by reduction of N-methylpyrrole with zinc and hydrochloric acid (132) and, together with the trimer, by mercuric acetate dehydrogenation of N-methylpyrrolidine (131). J -Pyrroline-N-oxides form dimers in a similar manner (302). Treatment of 1,2-dimethyl-zl -piperideine with formaldehyde, producing l-methyl-3-acetylpiperidine (603), serves as an example of a mixed aldol reaction (Scheme 18). 

In related work, the reactions of hydrogen peroxide with iron(II) complexes, including Feu(edta), were examined.3 Some experiments were carried out with added 5.5"-dimethyl-1-pyrroline-N-oxide (DMPO) as a trapping reagent fa so-called spin trap) for HO. These experiments were done to learn whether HO was truly as free as it is when generated photochemically. The hydroxyl radical adduct was indeed detected. but for some (not all) iron complexes evidence was obtained for an additional oxidizing intermediate, presumably an oxo-iron complex. 

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). 

FIGU RE 10.1 The structure of DMPO. The diamagnetic compound 5,5-dimethyl-l-pyrroline-iV-oxide reacts with an unstable radical R to form a relatively stable radical adduct. 

The scavenging ability toward O2 can also be measured by using electron spin resonance (ESR) spectrometry. The 02 anion is trapped with 5,5-dimethyl-1-pyrroline TV-oxidc (DMPO), and the resultant DMPO-OH adduct is detected by ESR using manganese oxide as internal standard. Noda and others (1997) used this technique to evaluate antioxidant activities of pomegranate fruit extract and its anthocyanidins (delphinidin, cyanidin, and pelargonidin). 

Addition of the Grignard reagent, generated in situ from (375), to nitrone (373) or to 2,5-dimethyl-l-pyrroline-A-oxide, affords biradical (379) or nitrone containing monoradical (380). Furthermore, (380) can be transformed into biradical (381) and triradical (382) (Scheme 2.165) (620). 

The /V -hydroxylamino compounds (404) and (405), obtained from the reaction of tert-butyl acetate with 3,4-dihydroisoquinoline-A-oxide or 5,5-dimethyl-pyrroline-/V-oxide, when boiled in methylene chloride in the presence of triphenylphosphine, carbon tetrachloride and triethylamine, are transformed to (1,2,3,4- tetrahydroisoquinolin-l-ilidene) acetate (406) or (pyrrolidin-2-ilidene) acetate (407) (Scheme 2.181) (645). 

There is some evidence, from EPR spectroscopy and analysis of spin-trapped adducts, to suggest that OH may indeed be formed by activated neutrophils. However, caution must be exercised in interpreting such data because 02"-generated adducts may decay to form adducts that resemble those generated directly from -OH. For example, 5,5-dimethyl-l-pyrroline-l-oxide (DMPO) can react with C>2 to form DMPO-OOH, and with OH to form DMPO-OH formation of the latter adduct in phagocytosing neutrophils is taken as evidence for OH formation. However, two facts must be considered ... 

Duchenne muscular dystrophy dimethyl formamide 5,5-dimethyl-1 -pyrroline-1 -oxide deoxynucleic acid diphenylene iodonium endothelium-derived relaxing factor epidermal growth factor early growth phase response gene ethyleneglycol- bis- (p- aminoethyl)-N,N,N, N -tetraacetic acid... 

The use of nitrone scavengers was precedented by the work of Iwamura and Inamoto (1967), who had used esr spectroscopy to detect the nitroxide formed by addition of cyanopropyl radicals to the cyclic nitrone, 5,5-dimethyl-pyrroline-N-oxide (DMPO) [2], and had actually isolated the cyanopropyl radical adduct of the nitrone [3]. 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Formation of phenylhydronitroxide radicals, DMPO (5,5-dimethyl-l-pyrroline-7V-oxide)/glutathiyl and DMPO/hemoglobin thiyl free radical adducts has been detected in erythrocytes of rats in vivo after administration of nitrosobenzene and phenylhydroxylamine, respectively92,94. The data, however, could also be interpreted in a different way ... 

In this type of spin traps, 5,5-dimethyl-l-pyrroline-Af-oxide (DMPO) deserves particular mention. DMPO is widely employed as a spin trap in the detection of transient radicals or ion-radicals in chemical and biological systems (see, e.g., Siraki et al. 2007). Characteristic ESR spectra arising from the formation of spin adducts are used for identification of specific spin species. In common opinion, such identification is unambiguous. However, in reactions with superoxide ion (Villamena et al. 2004, 2007b), carbon dioxide anion-radical (Villamena et al. 2006), or carbonate anion-radical (Villamena et al. 2007a), this spin trap gives rise to two adducts. Let us consider the case of carbonate anion-radical. The first trapped product arises from direct addition of carbonate anion-radical, second adduct arises from partial decarboxylation of the first one. Scheme 4.25 illustrates such reactions based on the example of carbonate anion-radical. 

Spectroscopic evidence for peroxy radical 51 was obtained from ESR. Spin trapping studies monitored by ESR have demonstrated that 02 reacts efficiently with 2-nitrobenzenesulfonyl chloride and results in the formation of the peroxy radical intermediate 51 (equation 88). The 5,5-dimethyl-l-pyrroline-l-oxide (DMPO) spin adduct of 51 shows the hyperfine coupling constants, aN = 1.8 G and aH = 10.1 G. 

Oxidation of a sulfide to sulfoxide is known to be an electrophilic reaction, in contrast with nucleophilic oxidation of sulfoxide to sulfone. Since 2-nitrobenzenesulhnyl ehloride/K02 oxidizes sulfides to sulfoxides selectively, intermediate 48 must be the actual active intermediate. Moreover, in the presence of l,4-diazabicyclo[2.2.2.]octane (DABCO), which is a radical capturing reagent, the oxidation of methyl phenyl sulfide to the sulfoxide was inhibited. In order to further detect the intermediate 48, pure 5,5-dimethyl-1-pyrroline-l-oxide (DMPO) was used as a trapping reagent and spin adduct was obtained223. The ESR spectrum of the DMPO spin adduct was obtained by the reaction of 02 with 2-nitrobenzenesulfinyl chloride (hyperfine coupling constants, aH = 10.0 G and aN = 12.8 G). 

ATP, adenosine 5 -triphosphate BH4, 5,6,7,8-tetrahydrobiopterin BMPO, 5- er -butoxycarbonyl-5-pyrroline A-oxide DBNBS, 3,5-dibromo-4-nitrosoben-zene sulfonate DEPMPO, 5-diethoxyphosphoryl-5-methyl-l-pyrroline A-ox-ide DMPO, 5,5-dimethyl- 1-pyrroline A-oxide EMPO, 5-ethoxycarbonyl-5-methyl-l-pyrroline A-oxide GSH, glutathione (y-L-glutamyl-L-cysteinyl-glycine) HRP, horseradish peroxidase MNP, 2-methyl-2-nitrosopropane MPO, myeloperoxidase NAD(P)H, fl-nicotinamine adenine dinucleotide (3 -phosphate), reduced from NMDA, A-methyl-D-aspartic acid PBN, N-tert-butyl-a-phenylnitrone PMN, polymorphonuclear lymphocyte POBN, a-(4-pyridyl-l-oxide)-A-fer -butylnitrone SOD, superoxide dismutase TEMP,... 

As a means of identifying the potent oxidant another approach was made. By the use of certain organic compounds one can infer the presence of a free radical by converting a highly unstable one such as OH to a much more stable compound which can accumulate in solution, rendering its detection by electron spin resonance possible. To measure the presence of OH the compound DMPO (5,5-dimethyl l-pyrroline-N-oxide) has been used The characteristic adduct of OH with... 

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