Nitronates formation

Scheme 2.183. Examples of the domino nitrone formation/1,3-dipolar cycloaddition.

As a result of Ag (I) catalyzed cyclization of allenic oximes (124) and (125), stable five- (126) and six-membered (127) cyclic nitrones were obtained (Scheme 2.46) (298a). Recently, a novel method of pyrroline-type nitrone formation via P-allenyl-oxime cyclization has been described (298b). 

A general method for nitrone formation is based on the interaction of nitro compounds with carbanions. Interaction between nitroso compounds (175) and anions of aliphatic nitro compounds (178) leads to nitrones (179). The source of anions are metal salts of nitro compounds, triethylamines, and trimethylsilylni-tronates (Scheme 2.63) (334, 335). 

FIGURE 4.86 Oxidation of a secondary amine to a hydroxylamine followed by nitrone formation. 

Correlative studies revealed that the faster the rate of nitronate formation, the higher the yields of the hydroxamic acids130 (equations 103 and 104). 

Hydrolysis of nitrones, oximes and hydroxamic acids is frequently used as a final step in the preparation of substituted hydroxylamines. Although hydrolysis is the most commonly utilized method for oximes, oxime ethers and nitrones, formation of sensitive hydroxylamines can also be achieved under milder reaction conditions by treatment of... 

The versatility of 5-nitrosopyrimidines in pteridine syntheses was noticed by Pachter (64MI21603) during modification of the Timmis condensation between (262) and benzyl methyl ketone simple condensation leads to 4-amino-7-methyl-2,6-diphenylpteridine (264) but in the presence of cyanide ion 4,7-diamino-2,6-diphenylpteridine (265) is formed (equation 90). The mechanism of this reaction is still uncertain (63JOC1187) it may involve an oxidation of an intermediate hydroxylamine derivative, nitrone formation similar to the Krohnke reaction, or nucleophilic addition of the cyanide ion to the Schiff s base function (266) followed by cyclization to a 7-amino-5,6-dihydropteridine derivative (267), oxidation to a quinonoid-type product (268) and loss of the acyl group (equation 91). Extension of these principles to a-aryl- and a-alkyl-acetoacetonitriles omits the oxidation step and gives higher yields, and forms 6-alkyl-7-aminopteridines, which cannot be obtained directly from simple aliphatic ketones. 

Moreover, biotransformation of secondary arylalkylamines also affords nitrones. Thus, N-oxygenation of a series of 4-substituted iV-benzylanilines in liver microsomal preparations from various animal species has been detected to be a minor pathway of metabolism, usually generating a,7V-diphenylnitrones (34) in a species-dependent manner26. Nitrone formation was most abundant in liver, kidney and lung53. There was a clear sex difference... 

Further possibilities for nonenzymatic nitrone formation include the disproportionation of nitroxides in cases where the nitroxyl functionality is attached to an a-carbon bearing at least one hydrogen142 (equation 14), or the rearrangement of certain N-hydroxy compounds to the thermodynamically more stable tautomeric forms, as has been observed for the formation of a-aminonitrone from N--hydroxy-7V-methylbenzamidine50 (equation 15). 

Scheme VII/5. Nitrone formation as a side reaction [12]. a) KOtBu, THF b) H2Q.

Nitrones, formation of, 153 p-Nitrophenylacetate, glyceraldehyde-3-phosphate dehydrogenase and, 21,45 Nitrous acid, catalase and, 388, 398 Nitrous oxide, catalase and, 400 Nonheme iron, see also Iron adenylyl sulfate reductase and, 282,... 

In Section III.E we noted that alkynes may be attacked by hydroxylamines at oxygen or nitrogen and illustrated nitrone formation in equation (111). The possibility of rearrangement of the nitrogen and oxygen products was also indicated. Hiere we give an example of the former (equation 176) . By comparison, isoxazole formation from keto alkynes is routine (equation 177) . 

Formation of an aminyl radical on the aromatic side of HPPD is a result of the NH-bond oxidation. The N-N coupling of aminyls accounts for the formation of interesting dimers, e.g. VI, able to be oxidized into nitroxide and nitrone. Formation of a C centered radical, mesomeric to the originally formed aminyl, should be expected. Thus, also other oligomeric products may be formed via C-N and C-C couplings. 

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