Azoxyarenes

Nitrosoarenes are readily formed by the oxidation of primary N-hydroxy arylamines and several mechanisms appear to be involved. These include 1) the metal-catalyzed oxidation/reduction to nitrosoarenes, azoxyarenes and arylamines (144) 2) the 02-dependent, metal-catalyzed oxidation to nitrosoarenes (145) 3) the 02-dependent, hemoglobin-mediated co-oxidation to nitrosoarenes and methe-moglobin (146) and 4) the 0 2-dependent conversion of N-hydroxy arylamines to nitrosoarenes, nitrosophenols and nitroarenes (147,148). Each of these processes can involve intermediate nitroxide radicals, superoxide anion radicals, hydrogen peroxide and hydroxyl radicals, all of which have been observed in model systems (149,151). Although these radicals are electrophilic and have been suggested to result in DNA damage (151,152), a causal relationship has not yet been established. Nitrosoarenes, on the other hand, are readily formed in in vitro metabolic incubations (2,153) and have been shown to react covalently with lipids (154), proteins (28,155) and GSH (17,156-159). Nitrosoarenes are also readily reduced to N-hydroxy arylamines by ascorbic acid (17,160) and by reduced pyridine nucleotides (9,161). 

Azo- and azoxyarenes have been repeatedly observed during reactions of nitrosoarenes with thiols5-7,11,29 33 35 36 38. The latter family presumably emerges from the interaction of the TV-hydroxy arylamine with unreacted nitrosoarene, a reaction proceeding even in neutral solutions2,6 58. The formation of azoarenes may be due to condensation of the end-product arylamine with still unreacted nitrosoarene59. 

Carbenes insert into the N=N bond of azo compounds and the unstable adducts rearrange spontaneously to produce benzopyrazoles (e.g. Scheme 7.31) [37,38], The reactions of azo compounds with dichlorocarbene is also catalysed by tertiary amines [36] and, under such conditions, azoxyarenes produce the benzimidazoles, presum-... 

Beim Erhitzen von Arylaziden mit Nitroso-benzolen bilden sich Azoxyarene. Brauchbare Ausbeuten werden allerdings nur dann erzielt, wenn das Arylazid einen elektronenspen-denden Substituenten wie Methyl oder Methoxy in para-Stellung tragt. Die Art der Substitution am Nitroso-aren ist ebenfalls bedeutsam, die hochsten Ausbeuten werden mit 4-Dimethylamino-l-nitroso-benzol erzielt. Von den beiden moglichen Azoxy-isomeren... 

Methods for the oxidation of azo to azoxy compounds have been reviewed.Typical oxidants are MCPBA and other peroxy acids and hydrogen peroxide. r-Butyl hydroperoxide is also an effective oxidant for azobenzenes in the presence of molybdenum hexacarbonyl. Trifluoroperacetic acid has been used to oxidize perfluoroazobenzene and other fluorinated azobenzenes to the azoxy compounds in high yield It is also capable of oxidizing azoxyarenes, such as compound (47), to the di-A(-oxides. 4... 

Deoxygenation of sulfoxides and azoxyarenes. This combination is superior to triphenylphosphine-iodine for deoxygenation of sulfoxides to sulfides (70-95% yield) and of azoxy benzenes to azobenzenes ( 90% yield, two examples). The reaction can be promoted by addition of sodium iodide. One advantage is that the by-product, HMPT, is soluble in water and easily removed. 

Nitroarenes, p-benzoquinone, a-bromoketones, a-bromophenylacetonitrile, and a,p-dibromostyrene are reduced by R jSl) to azoxyarenes, hydroquinone, ketones, 2,3-diphenylsuccinonitrile, and styrene, respectively (Scheme 14.56) [126J. The combined use of Ph2SbH and AICI3 reduces aldehydes to primary alcohols [48 a]. 

NUroarene reduction. Either azoarenes or azoxyarenes can be obtained on the reaction of nitroarenes with Bi-KOH in methanol. 

Selective hydrogenation of enones," particularly assisted by ultrasonic irradiation," is a synthetically valuable process. Ultrasonically activated nickel reduces nitroarenes to the azoxyarene stage. On the other hand, with formic acid or ammonium formate as the hydrogen source, the reduction results in arylamines."... 

Deoxygenation. Ultrasonically dispersed potassium reduces azoxyarenes to azoarenes at room temperature. 

Reduction of nitroarenes. This reagent in combination with zinc is a miid reducing agent, converting nitroarenes to azoxyarenes. 

Reduction of C—N and N=N bonds. The reduction of O-acyl oximes to primary amines and of both azoarenes and azoxyarenes to A.A-diarylhydrazines is readily achieved. 

One-step reduction of nitroarenes to azoxy- and azoarenes by the ball-milling technique was carried out by Suzuki [22], Milling of nitroarenes with bismuth balls (shots) gave as the major products azoxyarenes 76, while under N2 azoarenes 77 were formed predominantly (Scheme 6.27, Table 6.16). Addition of one drop of an inert organic solvent (hexane or benzene) led to complete formation of azoxyarenes. 

Similarly, aromatic nitroso compounds are deoxygenated. The nitrenes are intercepted to yield azoxyarenes (73). The internal trapping of the nitrene or the dipolar precursor (74) leads to heterocyclic products. Thus, 2-nitroso-biphenyl affords carbazole (75) in good yield. Spirodienyl intermediates are in-... 

Azo- and azoxyarenes are often found as by-products in reduction and carbonylation reactions of nitroarenes. It has been shown in several cases (see Chapter 3) that both of these two products can be further reduced and/or carbonylated by the same catalytic systems that reduce and carbonylate nitroarenes, to afford the same products. However, though the reduction from azoxy- to azoarene may be fast under certain conditions, the further reactions of azoarenes are very slow compared to the global reaction when the corresponding nitroarenes are used as substrates, indicating that, unlike nitrosoarenes, azo- and azoxyarenes cannot be intermediates in the main catalytic pathway. In at least... 

The NaBH4/l2 system has been also employed in the reduction of azoarenes and azoxyarenes to the corresponding hydrazobenzenes in good yields (eq 11) (45). 

Knight, G. T. and B. Saville. 1973. Hydrogen transfer from N-arylhydroxylamines to nitrosoarenes an accompaniment to azoxyarene formation. J. Chem. Soc. Perkin Trans. II 1973 1550-1553. 

Deoxygenation of Sulfoxides and Azoxyarenes. Sulfoxides are deoxygenated to sulfides under mild conditions with (Mc2N)3P activated with Iodine in acetonitrile (eq 15)." Equimolar ratios of the sulfoxide, (Me2N)3P, and I2 are generally employed. 

Yields are superior to those obtained with either (Me2N)3P/CCl4 or Ph3P/l2. Reaction time is reduced by addition of Sodium Iodide. Azoxyarenes, such as azoxybenzene, are converted to azoarenes with this reagent combination under similar mild conditions (eq 16). ... 

Nitroso Compounds. Similar treatment of nitrosobenzene resulted in a 75% yield of azobenzene. Aromatic A -nitroso amines have been converted into the secondary amines in 85-92% yields. Under photolytic conditions, azoxyarenes are produced. The choice of solvent is important. Dialkylni-trosoamines afford ureas (eq 26). ... 

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