Heteroaromatic N-oxidation

Relatively few heteroaromatic N-oxides occur in nature. The chemistry of compounds that contain the oxidized peptide bond (the so-called hydroxamic acids) and their role in iron metabolism have been reviewed (67SC1443). Another review deals with the natural occurrence of N-oxides (68MI1). 

One of the most rewarding and intensively investigated areas of research in heterocyclic chemistry has been the study of the photorearrangement of nitrones and heteroaromatic N-oxides. The subject was thoroughly reviewed in 1970.45 A more recent review concerned with the photochemistry of aromatic N-oxides has been published.46... 

The role of oxazirdines as intermediates in the rearrangement of heteroaromatic N-oxides has not been fully established although in most cases the formation of photoproducts can best be rationalized in terms of such intermediates. Rearrangement appears to be singlet-derived and competes with triplet-derived deoxygenation. 

Five-membered heteroaromatic N-oxides have been less systematically investigated although in most cases reaction via an intermediate oxaziridine appears to be involved. The imidazole 3-oxide 90, for example, is converted on irradiation in polar or nonpolar media to the diimine 91.7 5... 

A. R. Katritzky and J. M. Lagowski, Heteroaromatic N-Oxides. Academic Press, New York, 1970. 

Recently37, the importance of CT complexes in the chemistry of heteroaromatic N-oxides has been investigated in nucleophilic aromatic substitutions. Electron acceptors (tetracyanoethylene and p-benzoquinones) enhance the electrophilic ability of pyridine-N-oxide (and of quinoline-N-oxide) derivatives by forming donor-acceptor complexes which facilitate the reactions of nucleophiles on heteroaromatic substrates. 

Sulfotransferase activity is not restricted to minoxidil. The ability of other pyrimidine-, as well as pyridine-, triazine- and imidazole N-oxides to serve as substrates was investigated using soluble liver preparation and PAPS. The variety of structures studied indicated that heteroaromatic N-oxides are generally metabolized by sulfotransferases183. Presumably, all of the heterocycles tested were conjugated via their N-oxide oxygens. 

This review constitutes the first comprehensive description of the preparation, properties, and reactions of 5-membered heteroaromatic N-oxides derived from pyrazole, imidazole, 1,2,3-triazole, 1,2,4-triazole, and tetrazole. 

Chemical research of drugs by the Prof. M. Protiva group 91CCC2501. Contribution of Prof. M. Hamana to the chemistry of heteroaromatic N-oxides 92H(33)1. 

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. ... 

Methods of deoxygenation of nitrones (28), nitrile oxides (29), heteroaromatic N-oxides (30) and tertiary amine oxides (31) are described in this section. There are some reagents, such as trialkyl phosphites, which can deoxygenate compounds of all these types as well as those in the preceding section, whereas others are more limited in scope. Oae and coworkers have outlined three distinct mechanistic types of deoxygenation process, which are illustrated in Scheme 17. Clearly, a mechanism of type C will not apply to tertiary amine oxides (31) on the other hand, these compounds are more easily deoxygenated than heteroaromatic N-oxides, such as (30), by some reagents because the aromatic N-oxides are inherently more stable. 

No reports of any significance have been published on the photochemistry of nitrones during the year. Further investigations on the photorearrangement of heteroaromatic N-oxides and related systems have, however, been described in the literature. Debate on the possible intermediacy of oxaziridines in these transformations continues. A study of the effect of a magnetic field on the photorearrangement of isoquinoline N-oxide (60) in ethanol indicates that conversion into the lactam (61) does not... 

Although the multiplicity of excited states of heteroaromatic N-oxides is disputed, it is established that for pyridazine N-oxides the triplet state is involved in oxygen abstraction reactions, whereas the singlet state is involved in rearrangements and isomerizations. ... 

N-oxides can also be reduced. For example, the microbial deoxygenation of a series of aromatic and heteroaromatic N-oxide compounds, including quinoline N-oxides, isoquinoline N-oxides, 2-aryl-2H-benzotriazole 1-oxides, benzo[c]cinnoline N-oxide and azoxybenzene, has performed with bakers yeast-NaOH to afford quinolines and pyridines (291l... 

Azine approach. Heteroaromatic N-oxides will undergo 1,3-dipolar cycloaddition as a nitrone. Thus quinoxaline 1-oxide reacts with a variety of dipolarophiles, e.g. in the formation of the adduct (85). The 1,4-dioxide can form cycloadducts at both N-oxide functions. The adduct from 2//-l,4-benzoxazine 4-oxide and acrylonitrile is the isoxazolo[3,2-c][l,4]benzoxazine (86) (79T1771). 

The photochemistry of nitrones and heteroaromatic N-oxides has attracted much attention in previous years. Little of significance has been reported in the period covered by this... 

Many of the reactions of quinoxaline N-oxides are typical of those of heteroaromatic N-oxides in general. Thus the N-oxide function is readily reduced, nuclear substitution products are obtained on treatment with... 

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