Pyrroline-1-oxide

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... 

Spectroscopic evidence for peroxy radical 51 was obtained from ESR. Spin trapping studies monitored by ESR have demonstrated that O2 - reacts efficiently with 2-nitrobenzenesulfonyl chloride and results in the formation of the peroxy radical intermediate 51 (equation 88)223. The 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) spin adduct of 51 shows the hyperfine coupling constants, aN = 1.8 G and aH = 10.1 G. 

Another possible route to thienamycin (487) has utilized the dipolar cycloaddition of 1-pyrroline 1-oxide (482) with methyl crotonate (79TL4359). The reaction is highly stereoselective due to the operation of secondary orbital effects. The isoxazolidine (483), produced in 90% yield, was subjected to hydrogenolysis, and the resulting amino alcohol (484) was selectively blocked with hexamethyldisilazane to give (485). Treatment with ethylmagnesium bromide then gave /3-lactam (486 Scheme 107). 

Simple nonconjugated nitrones have a strong absorption maximum in the UV at around 230 nm. Acyclic nitrones are, in general, photo-chemically cyclized to the corresponding oxaziridines.148 The cyclic nitrone, 5,5-dimethyl-l-pyrroline 1-oxide (164) is similarly converted into the oxaziridine (165) by photolysis in ethanol/cyclohexane solution,146 and several 2-substituted 1-pyrroline 1-oxides were subsequently found to undergo the same cyclization in cyclohexane solution.147... 

Formula 475 (215). It is interesting to note, however, that 2-substituted 1-pyrroline-1-oxides do not photoisomerize (215). The corresponding 1-pyrrolines also do not give oxaziranes on peroxidation (215). 

Hydroxypyrrolidine (14), a colorless oil, is readily obtained from 1-ethylpyrrolidine by conversion to the 1-oxide and then heating to split out ethylene. Direct oxidation of pyrrolidine by performic acid gave only a 1% conversion (59CB1748). Oxidation of 14 with mercuric oxide now gave 1-pyrroline 1-oxide 15 as a distillable liquid. Phenylmagnesium bromide added across the dipolarophilic system of 15 yielded l-hydroxy-2-... 

Tufariello has reviewed his strategy for the synthesis of alkaloids (including necine bases) using the 1,3-dipolar cycloaddition of nitrones to alkenes.5 This work began with the synthesis of ( )-supinidine (7) from 1-pyrroline 1-oxide (see these Reports, Vol. 2, Ch. 4). A related approach has been used by Iwashita et al. in their synthesis of ( )-isoretronecanol (5).6 The stereochemistry of the exo-product (8), formed by regiospecific 1,3-dipolar cycloaddition of 1-pyrroline 1-oxide to dihydrofuran (Scheme 2), was confirmed by its conversion into... 

The seco-phenanthroindolizidine alkaloid septicine has been synthesized by a nitrone route. A cycloaddition of 1-pyrroline 1-oxide with 2,3-bis-(3,4-dimethoxyphenyl)butadiene gives two stereoisomeric isoxazolidines, one of which is converted into ( ) septicine.10 ( )-Tylophorine and 5-coniceine have been prepared by a new route that makes use of an intramolecular imino-Diels-Alder reaction.11 A stereoselective synthesis of 3,5-dialkyl-indolizidines has been applied to the synthesis of a stereoisomer of the trail pheromone of the Pharaoh ant and to a stereoisomer of gephyrotoxin 223.12 A stereoselective total synthesis of ( )-perhydrogephyrotoxin (21)13 and a simple synthesis of ( )-gephyran14 have been reported. 

Deoxygenation of a nitrone. Some years ago Todd and co-workers noted that 1-pyrroline-1-oxides can be obtained by reductive cyclization of a y-nitro ketone. This reaction was used recently in a synthesis of chlonns related to vitamin B,. Thus the nitro ketone 1 on reduction with zinc and acetic acid gives the pyrroline N-oxide 2 in high yield. The N-oxide is stable to triphenylphosphiue or trimethyl phosphite, but is reduced to the imine 3 in high yield by TiCl,. 

Examples of photorearrangement in nitrones and heteroaromatic N-oxides have again been described, and the subject has been critically reviewed. The hydroxyoxaziridines (81) have been prepared by irradiation of the corresponding 1-pyrroline 1-oxides (82), ° whereas photorearrangement of the dinitrone (83) gave the oxaziridines (84) and (85) and the lactam (86) oxaziridines (84), (85), and (86) were converted into the piperazine-2,5-dione (87) by further irradiation. ... 

In the case of 2-aryl-1-pyrroline 1-oxides (e.g., 108) ultraviolet irradiation has been shownto form only the isomer (e.g., 109) in which the oxa-ziridine ring is located on the same side of the five-membered ring as the substituent at C3. However, when the 2-substituent is alkyl or hydrogen, there is no stereoselectivity and the two isomers are formed in equal proportions. ... 

Oxazabicyclohexanes 134 have been postulated as undetected intermediates in the photolytic conversion of 2-acyl-1-pyrroline 1-oxides into pyrrolidinones and acyl pyrrolines. 

The oxidation of thioketene (245) by nitrones (246) of the 1-pyrroline 1-oxide type furnishes a-thiolactones (thiiranones) (247) (Equation (40)) <77AG(E)722>. But the oxidation of thioketene S-oxide gives thioketone S-oxide via thiiranone S-oxide (Scheme 87). 

With cyclic nitrones, where ( /Z) isomerization is not possible, the exo transition state is usually steri-cally preferred (equation 19-21). When steric factors in the endo and exo transition states are nearly the same, however, the existeiKe of bonding secondary orbital interactions in the endo transition state can tip the balaiKe in its favor, this appears to be the case for the reaction of methyl crotonate and 1-pyrroline 1-oxide (equation 22). ... 

Treatment of the quaternary ammonium salt PhC=CCH2NMe2CH2COPh Br" with sodium hydroxide gives, inter alia, the betaine (98). Controlled-potential electrolysis of 7-nitro-ketones on a mercury cathode yields 1-pyrroline 1-oxides, pyrrolines, or pyrrolidines, according to conditions thus the oxide (99) is obtained from the compound 02NCMe2CHPhCH2C0Ph. The pyrrolinone (101) results from autoxidation of the furan derivative (100). Irradiation of the amide (102) leads to the pyrrolidinone (103) by an unprecedented [1,6] shift of hydrogen. " ... 

The reaction of sulfenes with cyclic nitrones such as 1-pyrroline 1-oxide, in the presence of triethylamine, gave good yields (50-70%) of /Mminosulfonic acids which can easily be reduced to taurine derivatives (equation 142)227. 

Other than giving a very good account of the experimental qualitative behaviour, the above results probably offer a reasonable quantitative evaluation of the leacbon parameters. The apparent activation free enthdpy of the reaction of 1-pyrroline-1-oxide and 5,5-dimethyl-1-pyrroline-l-oxide with acrylonitrile have been meas-ured 2 in cyclohexane (20.4 0.4 and 21.7 0.4 kcal mol, respectively) and in di-chloromethane (22.4 0.2 and 23.010.8 kcal mol ) at 298K the rate constants for the reactions of H-nitrone have not been measured, but it can be stressed that N-monosubstituted nitrone, e.g, t-Bu-nitrone, exhibits a high reactivity in 1,3-dipolar cycloadditions, which is similar to that of 1-pyrroline-l-oxide so that the evaluations of Table 6 emerge to be surprisingly good. Moreover, the activation entropy of the reaction of 5,5-dimethyI-1-pyrroline-l-oxide with acrylonitrile in cyclohexane has been estimated -31,9 eu, a value which is well reproduced by our calculations in the gas-phase (-33.4, -31.1, footnote of Table 6). 

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