Hydroxamic acids nitroso derivatives

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. 

An intramolecular hetero-Diels-Alder reaction of enantiomerically pure iV-acyl nitroso derivatives 78, prepared from hydroxamic acids 77 by oxidation on treatment with Pr4NI04 in an aqueous medium, afforded a mixture of diastereomeric pyrido[l,2-A][l,2]oxazin-8-ones 79 and 80 (Scheme 5) <1996J(P1)1113, 20000L2955,... 

Acyl nitroso compounds (3, Scheme 7.2) contain a nitroso group (-N=0) directly attached to a carbonyl carbon. Oxidation of an N-acyl hydroxylamine derivative provides the most direct method for the preparation of acyl C-nitroso compounds [10]. Treatment of hydroxamic acids, N-hydroxy carbamates or N-hydroxyureas with sodium periodate or tetra-alkyl ammonium periodate salts results in the formation of the corresponding acyl nitroso species (Scheme 7.2) [11-14]. Other oxidants including the Dess-Martin periodinane and both ruthenium (II) and iridium (I) based species efficiently convert N-acyl hydroxylamines to the corresponding acyl nitroso compounds [15-18]. The Swern oxidation also provides a useful alternative procedure for the oxidative preparation of acyl nitroso species [19]. Horseradish peroxidase (HRP) catalyzed oxidation of N-hydroxyurea with hydrogen peroxide forms an acyl nitroso species, which can be trapped with 1, 3-cyclohexanone, giving evidence of the formation of these species with enzymatic oxidants [20]. 

In general, C-acyl nitroso compounds-9,10-dimethylanthracene cycloadducts derived from hydroxamic acids (-R = alkyl, aryl, ti/2 = 4.1 h for -R = -Ph at 60°C) decompose more slowly than those derived from N-hydroxycarbamates or N-hydroxyureas [11, 13, 14]. Further addition of alkyl groups to the N atom of N-hydroxyurea-derived cycloadducts produces a further increase in the rate of the retro-Diels-Alder reaction of these cycloadducts [36]. These general trends suggest the possibility of the development of acyl nitroso compound-9, 10-dimethylanthracene cycloadducts as a general class of HNO or NO donors with varied release profiles. 

Tetra-rt-propylammonium periodate oxidation of the hydroxamic acids 215 (R = CH2OH, CH20Me, CH2NHPI1 or CC Me), derived from L-proline, generates nitroso compounds 216, which, in the presence of cyclohexadiene, give mixtures of diastereomeric cycloadducts 217 in 79-89% yields and 26-68% de values (equation 115)109. 

Nitro-compounds fRNOj) are isomeric with nitrites, but their electronic structure, excited states and photochemistry are very different. There is no very low-lying (n.jt ) state, and nitroalkanes show n — 3i absorption with a maximum around 275 nm ( —201 mol - cm In cyclohexane solution, nitromethane (CH1NOi) is photoreduced to nitrosomethane(CH,NO, but nitroethane under the same conditions gives rise to a nitroso-dimer derived from the solvent CS.47). The latter process is probably initiated by cleavage of the carbon-nitrogen bond in the nitroalkane. In basic solution (when the nitroalkane is converted to a nitronate anion) irradiation can lead to efficient formation of a hydroxamic acid (S.48), and this reaction most likely proceeds through formation of an intermediate three-mem bered cyclic species. 

Studies on the addition of acyl nitroso compounds to 1,2-dihydropyridine derivatives have been described, and some of the results are shown in equation (38). It was found that the nitroso dienophiles produced from hydroxamic acids (100) reacted with dihydropyridine (99) at di erent rates and afforded the ratios of regioisomeric products indicated. Both the relative reaction rates and orientation are in accord with a HOMO-diene/LUMO-dienophile controlled process. 

Brief reports of cycloadditions with chiral acyl nitroso dienophiles have recently appeared. - In one study, acyl nitroso compound (101) derived from the corresponding hydroxamic acid was added to cy-clohexadiene to afford a 3.5 1 mixture of diastereomeric adducts (102) and (103). It was proposed that dienophile (101) reacts in the cyclic chelated form shown, since the related methyl ether which cannot internally hydrogen bond shows much lower diastereoselectivity. ... 

N-oxidation can occur in a number of ways to give either hydroxylamines from primary and secondary amines [Eqs. (11) and (12)], hydroxamic acids from amides, or N-oxides from tertiary amines [Eq. (13)]. The enzyme systems involved are either cytochrome P450 or a flavoprotein oxygenase. Hydroxylamines may be further oxidized to a nitro compound via a nitroso intermediate [Eq. (11)]. Oximes can be formed by rearrangement of the nitroso intermediate or N-hydroxylation of an imine, that could in turn be derived by dehydration of a hydroxylamine [Eq. (11)]. N-Oxides may be formed from both tertiary arylamines and alkylamines and from nitrogen in heterocyclic aromatic systems, such as a pyridine ring. 

An intramolecular nitroso Diels-Alder approach to the frog neurotoxin gephyrotoxin 223AB (25) has recently been reported (Scheme 3-XIV). Cyclization of the nitroso compound derived from hydroxamic acid 23 afforded the bicyclic adduct 24 in good yield, directly establishing two of... 

A number of types of compound can be considered as hydroxylamine derivatives. Hydroxamic acids have the general formula RC(OH)NOH and can be used to precipitate or extract a range of metal ions, including Zr, Th, Fe and Cr. Cupferron (ammonium iV-nitroso-Af-phenylhydroxylamine) and iV-substi-tuted phenylhydroxylamines such as iV-Benzoyl-IV-plienylliydroxylamine behave similarly to the hydroxamic acids, and are used for similar purposes. 

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