Hydroxamic acids, cyclic oxidation

No simple pteridine 1- or 3-oxides are yet known. If the AT-atom of an amide function is formally oxidized, tautomerism favours the cyclic hydroxamic acid structure, as found for 3-hydroxypteridin-4-one (55JA3927), 1-hydroxylumazine (64JOC408) and 2,4-diamino-8-hydroxypteridin-7-ones (75JOC2332). 

Cyclic hydroxamic acids and V-hydroxyimides are sufficiently acidic to be (9-methylated with diazomethane, although caution is necessary because complex secondary reactions may occur. N-Hydroxyisatin (105) reacted with diazomethane in acetone to give the products of ring expansion and further methylation (131, R = H or CH3). The benzalphthalimidine system (132) could not be methylated satisfactorily with diazomethane, but the V-methoxy compound was readil3 obtained by alkylation with methyl iodide and potassium carbonate in acetone. In the pyridine series, 1-benzyl-oxy and l-allyloxy-2-pyridones were formed by thermal isomeriza-tion of the corresponding 2-alkyloxypyridine V-oxides at 100°. 

In a very interesting paper Hu and Miller have described the synthesis of a L-lysine-derived cyclic hydroxamic acid 174 starting by the oxidation of protected Z-L-lysine 171 (formed from 170) with dimethyldioxirane (DMD) in acetone, followed by nitrone... 

The 1,8-naphthyridine di-iV-oxide (145), was prepared by oxidation of the corresponding base.154 Hydrolysis of 145 gave the 2-hydroxy derivative (146) in equilibrium with the cyclic hydroxamic acid (147).155... 

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... 

In one of our alternative approaches the lactol unit of the 2,4-dihydroxy-2i/-l,4-benzoxazin-3(4//)-one skeleton was developed by oxidation of the unsubstituted methylene function (Fig. (9)) [114]. The starting cyclic hydroxamic acids have been prepared by catalytic transfer hydrogenation of appropriate 2-nitrophenoxyacetate precursors with the sodium borohydride/Pt-C method. The oxidative transformation intended caused a need for protection of the hydroxamic acid moiety. From several... 

Fig. (9). Oxidative generation of the lactol unit by a-hydroxylation of a cyclic hydroxamic acid...

Oxidation of secondary amines, such as piperidine (94), with dimethyldioxirane (95) led to synthesis of cyclic hydroxamic acids (Scheme 52) (93ACS(47)1141). 

A further type of nitro-group rearrangement gives rise to a cyclic hydroxamic ether. Noland e.t aL describe the action of cold, dilute sulfuric acid on the sodium salt of 5-nitronorbornene (98), which results in conversion to the oxazinone (101). This complex rearrangement is rationalized by the sequence 98 101 involving intermediate formation of the nitrile oxide (99) and the hydroxamic acid (100). 

Alicyclic hydroxamic acids undergo several specific oxidative cleavage reactions which may be of diagnostic or preparative value. In the pyrrolidine series compounds of type 66 have been oxidized with sodium hypobromite or with periodates to give y-nitroso acids (113). Ozonolysis gives the corresponding y-nitro acids. The related cyclic aldonitrone.s are also oxidized by periodate to nitroso acids, presumably via the hydroxamic acids.This periodate fission was used in the complex degradation of J -nitrones derived from aconitine. 

More recently, the soundness of the electrochemical approach for the generation of PINO from HPI has been confirmed by using cyclic voltammetry at a rotating disk electrode. Anodic oxidation had been also employed for the generation of the aminoxyl radical from hydroxamic acids. ... 

---