Aminomethyl aromatic compounds

Phenols, secondary and tertiary aromatic amines, pyrroles, and indoles can be aminomethylated by treatment with formaldehyde and a secondary amine. Other aldehydes have sometimes been employed. Aminoalkylation is a special case of the Mannich reaction (16-15). When phenols and other activated aromatic compounds are treated withA-hydroxymethylchloroacetamide, amidomethylation takes place " ... 

Ferrocene is an aromatic compound similar to benzene. As the aromatic rings of ferrocene are coordinated by iron, ferrocene shows a higher basicity than that of benzene. Then an electrophilic reaction is liable to proceed. For example, Friedel-Crafts acylation, Mannich reaction (aminomethylation) and lithiation easily proceeds as shown in eqs. (15.12)-(15.14) [26]. 

Ferrocenes are aromatic compounds similar to benzene, as they have a high basicity, electrophilic substitution reactions such as Friedel-Crafts acylation (eq. (15.12)), metalation (eqs. (15.14) and (15.16), Scheme 15.1), Mannich reaction (aminomethylation, eq. (15.13)) and formylation (Scheme 15.1) are liable to proceed as described above. These products also have a high reactivity and they are used as raw materials for other ferrocene derivatives as shown in Schemes 15.1 and 15.2. For example, if one bridged ferrocene is obtained from Scheme 15.1 to form another bridge, lithium diisopropylamide (EDA) is reacted, oxidized with CuCl2, and reduced with LiAlH4 to afford a two bridged ferrocenophane as shown in eq. (15.23) [50,69]. 

Aminomethylation Reaction. The Hf(OTf)4-dopedMe3SiCl system was used as Lewis acid to catalyze the aminomethylation of electron-rich aromatic compounds. Suitable arenes include indoles, furans, pyrroles, thiophenes, and anilines, with new t)q)es of iV,0-acetals having a variety of functional groups, such as cyano, ester, bis(trimethylsilyl)amino, diallylamino, and cyclic amino moieties. This method allowed for the facile synthesis of nonnatural aromatic amino acid derivatives (eq 1). 4 Aminomethylation using a A, 0-acetal with a bis(trimethylsilyl)amino group was particularly successful in the direct preparation of a N-unsubstituted a-indolylglycine derivative, which required only a standard aqueous workup as the deprotective step. ... 

Whatever the detailed mechanism of the reaction between formaldehyde, secondary or primary amines and a suitably reactive aromatic compound, it is clear that essentially the Mannich aminomethylation is an electrophilic substitution. It is therefore not surprising that pyrrole reacts very readily with formaldehyde and secondary amines to give Mannich bases . If an excess of pyrrole is not maintained during the reaction, more highly substituted products result" 4, 1-Methylpyrrole reacts, if anything, more readily... 

Thus many compounds arc obtained (250, Table 24), which may be considered to be derived from C-alkylation of the nucleophilic reagent by the Mannich base. Alkyl ketonic and phenolic bases arc mostly involved in this reaction, which exhibits many analogies with aminomethylation, particularly concerning chemo- and regioselectivity on aromatic and heteroaromatic derivatives. Ring activation by means of hydroxy and amino substituents in the alkylation of pyridine and pyrimidine derivatives is also required. 

Permanent hair dyes are often derivatives of an aromatic amine, discovered as a hair dye in 1883, called /Mra-phenylenediamine (H2N-C6H4-NH2), including primary intermediates such as pcirci-aminophenol, dihydroxybenzene, 4-methylaminophenol, tetraaminopyrimidine, 2-aminomethyl-4-aminophenol, and / ara-aminodiphenylamine. The / zrra-phenylenedi-amine compound produces a black color, with its derivative parci- mmo-diphenylaminesulfonic acid used in blond formulations. Couplers are generally aromatic phenols or amines that have an available site that is subject to electrophilic interaction. Typical couplers include chemicals such as resorcinol, wrte-phenylenediamine, 2,4-diaminoanisole, mrm-aminophenol,... 

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