Arylation of primary alkylamine

Several reports on the application of the intermolecular arylation of primary alkylamines have appeared. For example, the reaction of primary amines with chloro 1,3 azoles has been used to produce the H-l-antihistaminic norastemizole [153]. As shown in Eq. (32), the palladium chemistry is dictated by the steric properties of the amines. This property creates selectivity that complements the thermal chemistry, which is dictated by amine nucleophilicity. These researchers have also shown that this high selectivity for arylation of primary over secondary amines with catalysts containing BINAP as ligand allows for the rapid assembly of other multiamino-based structures [154]. 

FIGURE 9. Josiphos ligand that generates highly active catalysts for the coupling of primary alkylamines with aryl chlorides... 

Phosphines that are tightly chelated to the metal center often achieve high selectivity of secondary over tertiary amine products in reactions of primary alkylamines with unhindered aryl halides. The chelation helps prevent competing /3-hydrogen elimination of the aryl palladium amido intermediate (vide infra). Additionally, the greater steric hindrance of bisphosphine palladium complexes, when compared to mono phosphine palladium complexes, prevents diarylation. Some ligands originally introduced by... 

The reactions of primary arylamines with aryl halides are simpler to catalyze than those of primary alkylamines because /3-hydrogen elimination will not compete with reductive elimination. However, diarylation of the aniline can be a competing process, and for some reason the original catalyst system containing P(o-tolyl)3 showed low activity for the reactions of aniline with aryl halides. 

A full paper detailing the conversion of primary alkylamines into the corresponding thiocyanates has appeared,and this important contribution to thiocyanate synthesis has now been extended to include aromatic derivatives. Thus, the readily prepared (56) reacts, in refluxing ethanol, with arylamines to give (57), which are smoothly pyrolysed to aryl thiocyanates in preparatively useful yields (Scheme 55). 

Primary arylfflnines, like primary alkylamines, for-m diazonium ion salts on nitro-sation. Ar-yl diazonium ions are considerably more stable than their- alkyl counterparts. Whereas alkyl diazonium ions decompose under the conditions of their for-mation, aryl diazonium salts are stable enough to be stored in aqueous solution at 0-5°C for a reasonable time. Loss of nitrogen from an aryl diazonium ion generates an unstable aryl cation and is much slower than loss of nitrogen from an alkyl diazonium ion. 

Primary amine (Section 22.1) An amine with a single alkyl or aryl substituent and two hydrogens an amine of the type RNH2 (primary alkylamine) or ArNH2 (primary aryl-amine). 

The N,N-diethylamide of salicylic acid is a useful ligand in conjunction with Cul and permits amination of aryl bromides by primary alkylamines.151... 

A great variety of 3-alkyl- and 3-aryl-1,2,4,5-tetrazines can also easily be alkylaminated when treated with appropriate primary alkylamines in the presence of potassium permanganate (Scheme 30). The yields vary depending on the size of the alkyl group in the amine. Attempts to introduce an arylamino group were unsuccessful. 

An alternative pathway when soluble alkoxide or silylamido bases are used involves reaction of an arylpalladium halide complex with the alkoxide or silylamide to form an intermediate alkoxide or amide. These complexes can react with amines to form the required amido aryl intermediates. The reaction of Pd(PPh3)(Ph)(//-OH) 2 with primary alkylamines to generate palladium amido complexes and water (Eq. (49)) [70, 280] gave an early indication that the conversion of an alkoxide to an amide could be occurring during the catalytic cycle. These reactions are reversible, but the equilibrium favors the amido complex. 

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