Arylamine reactions

Diazonium coupling reactions are typical electrophilic aromatic substitutions in which the positively charged diazonium ion is the electrophile that reacts with the electron-rich, ring of a phenol or arylamine. Reaction usually occurs at the para position, although ortho reaction can take place if the para position is blocked. 

Using the bulky AT-heterocyclic carbene 130 as a ligand for Pd(0) complexes Schneider and coworkers [104] have recently reported a novel synthetic strategy to five-, six- and seven-membered N-arylated heterocycles 131-135 via sequential Pd-catalyzed intra- and intermolecular arylamination reactions (Scheme 49). 

A -Arylaziridines were synthesized in very good yield by palladium-catalyzed N-arylamination reactions utilizing BINAP or xantphos as suitable ligands and either CS2CO3 or NaO/-Bu as a base <07S243>. 

Methylation of arylamines. Reaction of ArNH, with paraformaldehyde, CHjONa, and CH3OH results in N-(methoxymethyl)-N-arylamines (2), which slowly decompose to form a triazinane via an imine, ArN=CH, (a). The imine can be reduced by NaBH4 in CH,OH to ArNHCH, (3) in high yield. 

Primary arylamines. Reaction of aryl iodides with this reagent in refluxing pyridine leads to silyl-protected amines, convertible into free amines by methanolysis. ... 

Direct incorporation of arylamino fragments into heteroaromatic compounds has some features. Unfortunately, the oxidative amination and alkylami-nation procedures cannot be applied for arylamination, because of a reduced A-nucleophilic character, a high sensitivity of aromatic amines towards oxidation, and a low stability of arylamino-arylamination reactions are still rare. A vast majority of the known examples are intramolecular reactions, which are performed in the presence of mild oxidants, such as sulfur, chloranU, or nitrobenzene (for review, see [34]). In some cases, air oxidation of the intermediate 7 -complexes has been observed. In the series of nitroarenes the nitro group often acts as the hydride ion acceptor. Similarly, in arylamination of azaaromatics the cyclic C=N bmid can intercept the hydride ion. 

Only a few intermolecular oxidative arylamination reactions in the heterocyclic series have so far been reported. 5-AzacinnoUne, 1,2,4-triazines, 3-nitropyridines, and heterocyclic quinones are among those compounds which react with anilines or hetarylamines in the presence of a strong base. In fact, in order to perform these reactions metal salts of arylamides are needed as nucleophiles. For instance, interaction of 5-azacinnoline with arylamines in the presence of potassium hydroxide demands 20 days to complete the process with crucial access to air oxygen (Scheme 36) [89]. 

Compound III accumulates in the absence of glutamine. It is hydrolyzed to aminoribosylimidazolecarboxamide phosphate by hot HCl. It can be detected by the arylamine reaction and spectrophotometrically at 290 niM. The enzymes necessary for the synthesis of compound III have been separated from those required for its conversion to aminoribosylimidazole-carboxamide phosphate by treatment with protamine. 

---