Hydroxamic acids, cyclic reduction

Perhaps the most reliable method for the reductive cyclization of a nitro ester to a hydroxamic acid is that which involves treatment with sodium horohydride in the presence of palladium on charcoal. Although under these conditions aromatic nitro compounds are reduced to amines, o-nitro esters such as 53, in which the ester group is suitably oriented with respect to the nitro group, give good yields of cyclic hydroxamic acids (54). Coutts and his co-... 

In one particular example, an interesting intramolecular acylation occurred. Reduction of cis-iVi-acetyl-o-nitrobenzylideneoxindole (55) gave rise to a cyclic hydroxamic acid, assigned structure 56. 

Reduction of cyclic hydroxamic acids generally leads to lactams or the corresponding amines. Chemical methods have frequently been preferred to catalytic hydrogenation, probably because the choice of... 

Hydroxamic acids constitute an important class of siderophores, which play a major role in iron solubilization and transport. Some of them are important as therapeutic agents. The Michael addition of nitroacetyl proline esters to allyl acrylate followed by Pd(0)-catalyzed intramolecular allyl transfer and subsequent reduction of the nitro group yields a novel class of cyclic hydroxamic acids related to pyroglutamic acid (Scheme 5.9).85... 

The electrochemical reduction of the corresponding nitrophenylpyridine or pyridinium derivatives only produces cyclic hydroxamic acids. 

The literature contains several references to reductive cyclizations producing cyclic hydroxamic acids like those described above, though not in solid-phase chemistry.43-47 We showed that this reaction competes well with lactam formation. The relative extent of these two reaction pathways is highly dependent on the presence and the nature of other heteroatoms and substituents around the ring system as well as on the conditions used to effect the reduction. 

The cyclohexene 121, which was readily accessible from the Diels-Alder reaction of methyl hexa-3,5-dienoate and 3,4-methylenedioxy-(3-nitrostyrene (108), served as the starting point for another formal total synthesis of ( )-lycorine (1) (Scheme 11) (113). In the event dissolving metal reduction of 121 with zinc followed by reduction of the intermediate cyclic hydroxamic acid with lithium diethoxyaluminum hydride provided the secondary amine 122. Transformation of 122 to the tetracyclic lactam 123 was achieved by sequential treatment with ethyl chloroformate and Bischler-Napieralski cyclization of the resulting carbamate with phosphorus oxychloride. Since attempts to effect cleanly the direct allylic oxidation of 123 to provide an intermediate suitable for subsequent elaboration to ( )-lycorine (1) were unsuccessful, a stepwise protocol was devised. Namely, addition of phenylselenyl bromide to 123 in acetic acid followed by hydrolysis of the intermediate acetates gave a mixture of two hydroxy se-lenides. Oxidative elimination of phenylselenous acid from the minor product afforded the allylic alcohol 124, whereas the major hydroxy selenide was resistant to oxidation and elimination. When 124 was treated with a small amount of acetic anhydride and sulfuric acid in acetic acid, the main product was the rearranged acetate 67, which had been previously converted to ( )-lycorine (108). 

The nitrile group of (172) reacts with hydroxylamine to give the hydroxyamidine (173). Reduction of the nitro to an amino group and then treatment with trimethyl orthoformate gives the aminopyrazolopyrimidine (V-oxide (174) which, with care, can be hydrolyzed to the cyclic hydroxamic acid (175 Scheme 54) (70JHC863). 

MisceUaneous Reactions.—Details of the formation of nitrous oxide by photofragmentation of methyl nitrite have been reported.Photorearrangement is observed, however, on irradiation of the nitrites (183) derived from 6-methyl- and 4,4,6-trimethyl-cholest-5-en-3-ol to give the cyclic hydroxamic acids (184). There is ample precedent for these transformations, the likely pathway for which is outlined in Scheme 12. An alkoxyl radical (185) is also thought to be involved in the photochemicaUy induced conversion of O-nitrobenzoin (186) into benzaldehyde (187) and 2-phenylbenzo[b]furan (188). Reductive photoelimination of vicinal dinitro-groups takes place by... 

Similarly (Scheme 42) (82JOC1302), oxidation of hydroxamic acid 313 in the presence of 9,10-dimethylanthracene gave an 82% yield of the hetero Diels-Alder adduct 314. This product was decomposed in refluxing toluene to afford a quantitative yield of the ene adduct 315. The cyclic hydroxamic acid 315 was converted to the corresponding lactam (316) by TiClj reduction. The... 

Sometimes a cathodic substitution reaction takes place during the reduction of o-substituted nitrobenzenes thus, the reduction of 2-nitrophenoxyacetic acid [52] in 2 A hydrochloric acid (50% ethanol) yielded 5-chloro-2i7-l,4-benzoxazin-3(4H)-one rather than the expected cyclic hydroxamic acid [52]. In the presence of another nucleophile Y (e.g., thiocyanate), a ring substitution with this reagent occurs. 

Cyclic hydroxamic acids are formed by partial reduction of A -(nitrophenyl)gly-cine in an acidic medium at 60 C. The glycine ester (72.6) may be heated with a base to give the dione. 

Claisen rearrangements, in nitrogen heterocyclic systems, 8, 143 Complex metal hydrides, reduction of nitrogen heterocycles with, 5, 45 Covalent hydration, in heteroaromatic compounds, 4, 1, 43 Cyclic enamines and iinines, 6,147 Cyclic hydroxamic acids, 10, 199 Cyclic peroxides, 8, 165... 

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