Aromatic A-oxides

9 Aromatic A -Oxides. - Tirapazamine is a bioreductive anticancer agent that is particularly toxic to hypoxic cells. The protection afforded from such drugs by oxygen is believed to indicate that oxygen radicals are not primarily responsible for their cytotoxicity, which probably results from DNA damage induced directly by reactive metabolites. Patterson and Taiwo have observed DMPO adducts of-OH, 02 and a carbon-centred radical upon the incubation 

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A number of other miscellaneous transformations of hetero-aromatic A-oxides have been reported. Of particular interest is the application189 of the photolysis of 2-cyanoquinoline 1-oxides to the synthesis of 1-aminocarbostyrils 2-cyano-4-methylquinoline 1-oxide is converted into the quinolinone by irradiation in dichloromethane solution in the presence of a secondary amine, and the conversion presumably takes place via the intermediate oxaziridine [Eq. (45)]. 

Aromatic A-oxides undergo 1,3-dipolar cycloaddition reactions. Phenyl isocyanate with pyridine 1-oxides involves a reaction sequence which in the end gives a 2-anilinopyridine. The initial product is the ring-fused 1,2-dihydropyridine 1-oxide (600), which rapidly undergoes a 1,5-sigmatropic shift to its more stable 2,3-dihydro counterpart (601) which is then aromatized by C02 expulsion (76JHC171,80H(14)19). 

There are a number of thermal and photochemical reactions for which oxaziridine intermediates have been proposed but never isolated. These include, among others, the photochemical Beckmann rearrangement of oximes, many photochemical reactions of aromatic A -oxides, and the thermal rearrangement of nitrones to amides. A brief discussion of the first two seems warranted in this review because they have been studied extensively and some strong inferential evidence for oxaziridine intermediates has been obtained. 

All attempts to supply physical evidence for the formation of oxaziridines as intermediates in the photolysis of aromatic A -oxides have met with scanty success, so investigators have relied on indirect evidence. Theoretical calculations seem to agree that, in aromatic A -oxides, oxaziridines do not arise from the ground state but very likely from the first excited singlet state. A comprehensive critical review of this subject has appeared. ... 

Typical structures of the complexes ((127)-(132)) are illustrated (see also Scheme 19). All the compounds have been characterized by X-ray crystallography, except for (127) and (130) for the latter, the crystal structure of a V111 analog is available.630-636 In addition, a series of articles by Kanno et al. on isomerization and racemization of the Cr111 complexes of substituted 2,2 -bipyridine-l,l -dioxide ligands637-639 continued the earlier works of these authors on the stereochemistry of metal complexes with bidentate aromatic A-oxide ligands.1... 

The synthesis of oxazole A-oxidcs from a-hydroxyimino ketones and aldehydes, and their reductive conversion into oxazoles has already been described (Section II, K). Attempted A-oxidation of 2,5-diphenyloxazole with hydrogen peroxide in acetic acid failed it led to ring-opening.418 Oxazole A-oxides show a strong absorption band around 1240 cm-1 in their infrared spectra, indicative of an aromatic A-oxide group.419 Recently, NMR data for several oxazole A-oxides have been reported.148... 

Figure 5 Degradation of alkyl-substituted aromatics, (a) Oxidation of side chain toluene (R = H) andp-xylene (R = CH3>. (b) Removal after ring cleavage o- and m-cresol. (c) Different end products p-cresol.

A very large number of nickel(II) complexes with a variety of aromatic A-oxides n i .is43 selection of the most representative aromatic A-oxides are reported in T 87 together with their more significant nickel(II) complexes. 

The rate of Jacobsen-Katsuki epoxidation can be enhanced in the presence of additives such as pyridine A-oxide or related aromatic A-oxides. For example, in a synthesis of the potassium channel activator BRL-55834, only 0.1 mol% of the (5,5)-(salen)Mn(III)Cl catalyst 58 was required for efficient epoxidation of the chromene 62 in the presence of 0.1 mol% isoquinoline A-oxide (5.68). In the... 

Ring construction and ring transformation methods involving aromatic A-oxides provide a number of routes to 1,3-oxazepine derivatives and benz- or dibenz-fused analogues. However, extensive scope exists for the development of new ring construction approaches, for example... 

A number of aza-aromatic A-oxides, such as pyridine, quinoline, and pyrimidine A-oxides, were converted into the corresponding a-imidazolyl-substituted heteroarenes in good yields on treatment with sulfuryl diimidazole in nonpolar solvents at elevated temperatures (Scheme 19) [45]. 

Other reviews that have appeared this year include those on radical combination and disproportionation reactions, theoretical models for addition and abstraction reactions, homolytic addition reactions of dialkylaminyl radicals and the chemistry of nitroarene and aromatic A -oxide radicals. ... 

The generation and reactivity of a-oxo gold carbenoids by the action of gold(I) catalyst in the presence of aromatic A-oxides have been detailed. ... 

If an adsorbed chemical group (anchor) is more strongly bound to the surface than a solvent molecule would be at that site, an equiHbrium expression may be written for the displacement of solvent by adsorbate. Adsorption is particularly strong if the chemical nature of the adsorbed group is similar to that of the particle surface for example, in aqueous systems perfluoroalkane groups adsorb weU on polytetrafluoroethene particles and aromatic polyethene oxides adsorb weU on polystyrene. 

The oxidative coupling of 2,6-dimethylphenol to yield poly(phenylene oxide) represents 90—95% of the consumption of 2,6-dimethylphenol (68). The oxidation with air is catalyzed by a copper—amine complex. The poly(phenylene oxide) derived from 2,6-dimethylphenol is blended with other polymers, primarily high impact polystyrene, and the resulting alloy is widely used in housings for business machines, electronic equipment and in the manufacture of automobiles (see Polyethers, aromatic). A minor use of 2,6-dimethylphenol involves its oxidative coupling to... 

Amine oxides, known as A[-oxides of tertiary amines, are classified as aromatic or aliphatic, depending on whether the nitrogen is part of an aromatic ring system or not. This stmctural difference accounts for the difference in chemical and physical properties between the two types. 

Aromatic amine oxides, produced on a much smaller scale and having some pharmaceutical importance, do not demonstrate the surface-acting properties that the aUphatic amine oxides do. 

Reduction. Just as aromatic amine oxides are resistant to the foregoing decomposition reactions, they are more resistant than ahphatic amine oxides to reduction. Ahphatic amine oxides are readily reduced to tertiary amines by sulfurous acid at room temperature in contrast, few aromatic amine oxides can be reduced under these conditions. The ahphatic amine oxides can also be reduced by catalytic hydrogenation (27), with 2inc in acid, or with staimous chloride (28). For the aromatic amine oxides, catalytic hydrogenation with Raney nickel is a fairly general means of deoxygenation (29). Iron in acetic acid (30), phosphoms trichloride (31), and titanium trichloride (32) are also widely used systems for deoxygenation of aromatic amine oxides. 

Substitution Reactions. Aromatic heterocycHc A/-oxides undergo both electrophilic and nucleophilic substitution because the dipolar N-oxide group is both an electron donor and an electron acceptor, giving rise to the resonance stmctures ... 

Owiag to the lower basicity of the parent amines, aromatic amine oxides cannot be formed directiy by hydrogen peroxide oxidation. These compounds may be obtained by oxidation of the corresponding amine with a peracid perbenzoic, monoperphthaUc, and monopermaleic acids have been employed. 

When a hydroxyazole can tautomerize to a non-aromatic structure, oxidation at an annular sulfur atom becomes easy, e.g. as in Scheme 9 (79AHC 25)83). 

A-Oxidation with peracids (Section 4.04.2.1.3) and the transformation of pyrazoles into 4,4-dihalogeno-2-pyrazolin-5-ones (Section 4.04.2.1.4(v)) have already been discussed. Transformation of non-aromatic 2-pyrazolin-5-ones into the 4-oxo derivatives will be examined in Section 4.04.2.2.l(ii). 

Amine oxides, prepared to protect tertiary amines during methylation and to prevent their protonation in diazotized aminopyridines, can be cleaved by reduction (e.g., SO2/H2O, 1 h, 22°, 63% yield H2/Pd-C, AcOH, AC2O, 7 h, 91% yield Zn/HCl, 30% yield). Photolytic reduction of an aromatic amine oxide has been reported [i.e., 4-nitropyridine A-oxide, 300 nm, (MeO)3PO/CH2Cl2, 15 min, 85-95% yieldl. ... 

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