Nucleophilic aromatic oxidative substitution

Nucleophilic aromatic substitutions involving loss of hydrogen are known. The reaction usually occurs with oxidation of the intermediate either intramoleculady or by an added oxidizing agent such as air or iodine. A noteworthy example is the formation of 6-methoxy-2-nitrobenzonitrile from reaction of 1,3-dinitrobenzene with a methanol solution of potassium cyanide. In this reaction it appears that the nitro compound itself functions as the oxidizing agent (10). 

Hexa-fluorobisphenol A (HFBPA) based polysulfone and poly(arylene ether phosphine oxide) were prepared by nucleophilic aromatic substitution similar to that of bisphenol-A-based polysulfone and poly(arylene ether phosphine oxide).11... 

Chapter 11 focuses on aromatic substitution, including electrophilic aromatic substitution, reactions of diazonium ions, and palladium-catalyzed nucleophilic aromatic substitution. Chapter 12 discusses oxidation reactions and is organized on the basis of functional group transformations. Oxidants are subdivided as transition metals, oxygen and peroxides, and other oxidants. 

Amination of aromatic nitro compounds is a very important process in both industry and laboratory. A simple synthesis of 4-aminodiphenyl amine (4-ADPA) has been achieved by utilizing a nucleophilic aromatic substitution. 4-ADPA is a key intermediate in the rubber chemical family of antioxidants. By means of a nucleophibc attack of the anilide anion on a nitrobenzene, a o-complex is formed first, which is then converted into 4-nitrosodiphenylamine and 4-nitrodiphenylamine by intra- and intermolecular oxidation. Catalytic hydrogenation finally affords 4-ADPA. Azobenzene, which is formed as a by-product, can be hydrogenated to aniline and thus recycled into the process. Switching this new atom-economy route allows for a dramatic reduction of chemical waste (Scheme 9.9).73 The United States Environmental Protection Agency gave the Green Chemistry Award for this process in 1998.74... 

Pyridine A-oxides were converted to tetrazolo[l,5-a]pyridines 172 by heating in the presence sulfonyl or phosphoryl azides and pyridine in the absence of solvent <06JOC9540>. 3-R-5-Trinitromethyltetrazolo[l,5-a]-l,3,5-triazin-7-ones 173 have been prepared from the alkylation of 5-trinitromethyltetrazolo[l,5-a]-l,3,5-triazin-7-one silver salt with different alkylation agents <06CHE417>. The use of 2-fluorophenylisocyanide in the combinatorial Ugi-tetrazole reaction followed by a nucleophilic aromatic substitution afforded tricylic tetrazolo[l,5-a]quinoxaline 174 in good yields and with high diversity <06TL2041>. 

Most syntheses of naturally occurring phenazines, though, are based on a two-step elaboration of the central heterocycle of the phenazine [78]. The first key step involves the generation of orf/zo-monosubstituted 88 or orf/zo, ortho -disubstituted diphenylamines 89-91 via nucleophilic aromatic substitution. Ring formation is then achieved by means of reductive or oxidative cyclization, for which a number of efficient methods are available. The main flaw of this approach is the synthesis of the substituted diphenylamines via nucleophilic aromatic substitution, as this reaction often can only be performed under strongly basic reaction conditions and at high temperatures. In addition, the diphenylamines required may only be achieved with certain substitution patterns with high yields. 

The selective oxidation of the activated aromatic ring, substituted with electron-donating hydroxy or methoxy groups, can be perfomed at relatively low electrode potential (Ep = 0.3-1.2 V vs SCE) and ring closure is the result of the intramolecular nucleophilic attack of an amino group on the oxidized aromatic ring. 

There are a wide number of reports regarding nucleophilic aromatic substitution a to nitrogen in 1,10-phenanthro-line 48. Eor example, the aryllithium reagent 49 adds to 1,10-phenanthroline 48 and on oxidative workup yields... 

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. 

Kita and Tohma found that exposure of p-substituted phenol ethers to [bis(tri-fluoroacetoxy)iodo]benzene 12 in the presence of some nucleophiles in polar, less nucleophilic solvents results in direct nucleophilic aromatic substitution [Eq. (84)] [156]. Involvement of a single-electron transfer (SET) from phenol ethers to A3-iodane 12 generating arene cation radicals was suggested by the detailed UV-vis and ESR studies. SET was involved in the oxidative biaryl coupling of phenol ethers by 12 in the presence of BF3-Et20 [157]. 

In 1,2-type azole N-oxides, leaving groups at the 3- and 5-positions are activated toward nucleophilic aromatic substitution since nucleophilic attack at these positions renders intermediates 28 and 34 in which the positive N-oxide nitrogen atom adopts the negative charge brought to the adduct by the nucleophile. Nucleophilic attack at the 4-substituted isomer 30 would give rise to intermediates like 31 in which such stabilization is impossible (Scheme 6). 

Substituted imidazole 1-oxides 228 are predicted to be activated toward electrophilic aromatic substitution, nucleophilic aromatic substitution, and metallation as described in Section 1. Nevertheless little information about the reactivity of imidazole 1-oxides in these processes exists. The reason for this lack may be the high polarity of the imidazole 1-oxides, which makes it difficult to find suitable reaction solvents. Another obstacle is that no method for complete drying of imidazole 1-oxides exists and dry starting material is instrumental for successful metallation. Well documented and useful is the reaction of imidazole 1-oxide 228 with alkylation and acylation reagents, their function as 1,3-dipoles in cycloadditions, and their palladium-catalyzed direct arylation. 

---