Arylated anilines Subject

Some time ago, Holliman and co-workers illustrated a method for synthesizing polysubstituted phenazines by reductive cyclization of o-nitrodiphenylamine. However, the yield was poor when competitive cyclizations occurred <70CC1423>. Recently, Kamikawa and co-workers reported a more efficient method to synthesize phenazines using sequential aniline arylation, which was first introduced by Buchwald <97JOC1264>. Regioselective bromination of o-nitrodiphenylamine 226 with bromine in the presence of sodium bicarbonate yielded 227 which was subjected to the Buchwald conditions to provide the desired phenazine 228 and the eliminated product 229 <00TL355>. The former compound is a proposed intermediate for the synthesis of the radical scavenger benthocyanin A. 

One limitation is that this re=action cannot be used for rearrangement of amides of aryl carboxylic acids because anilines are subject to further oxidation. ... 

In the laboratory of R. Bihovsky, a series of peptide mimetic aldehyde inhibitors of calpain I was prepared in which the P2 and P3 amino acids were replaced with substituted 3,4-dihydro-1,2-benzothiazine-3-carboxylate-1,1-dioxides. The synthesis began with the diazotization of the substituted aniline substrate using sodium nitrite and hydrochloric acid. The aqueous solution of the corresponding diazonium chloride product was added dropwise to the solution of acrylonitrile in a water-acetone mixture, which contained catalytic amounts of copper(ll) chloride. This Meerwein arylation step afforded the chloronitrile derivative, which was subjected to sulfonation with chlorosulfonic acid, and the resulting sulfonyl chloride was treated with the solution of ammonia in dioxane to give the desired 3,4-dihydro-1,2-benzothiazine-2-carboxamide. 

In 2007, Fujii, Ohno and their coworkers developed an efficient one-pot Buch-wald-Hartwig /V-arylation and oxidative coupling reaction to synthesize carbazoles (Scheme 27) [95]. Typically, Pd-catalyzed N-arylation of anilines with aryl triflates was conducted in toluene under the standard conditions. After completion of the N-ary I at ion as determined by TLC, acetic acid was added and an oxygen balloon was connected to the reaction flask (oxygen conditions) or it was subjected to air by an open system (air conditions). The protocol afforded various types of functionalized carbazoles in good to excellent yields (46->99%). 

Alkyl-substituted aryl bromides and triflates were subjected to react with aniline derivatives in the presence of NaOtBu as the base and provided the sp -amidation products in good to high yields. Substrates prone to oxidation or sensitive to acidic conditions were cleanly converted, underscoring the complementarity of the method. 

Similarly, aniline was subjected to cross coupling with substituted arylboronic acids and o-, p-substituted anilines with phenylboronic acid, and the corresponding Ai-aryl amines were obtained in satisfactory yields (Table 37, entries 1-9). The coupling of alkylamines with phenylboronic acid gave the W-alkyl anilines in moderate yields (Table 37, entries 10-14). However, the reaction of amides and sulfonamides with phenylboronic acid afforded the corresponding products albeit in lower yields (Table 37, entries 15 and 16). 

An illustration of the abiotic reactions that are believed to dominate the fate of aromatic amines in soils and sediments is given in Figure 12. In oxic environments, numerous reactants and reaction schemes have been suggested to account for the rapid disappearance of anilines and related compounds. Many of the products obtained from the oxidation of aromatic amines can be rationalized by examination of the reactivity of the aryl-amino radical, ArNHV Delocalization by resonance stabilizes the aryl-amino radical but makes the ortho- and para- positions of the ring subject to reactions (41, 46). 

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