Aminomethyl derivatives phenols

Deaminomethylation of Mannich bases may also occur in the presence of electrophilic species, capable of replacing the aminomethyl group linked to the substrate moiety, such as, for example, diazonium salts acting on Mannich bases of phenols and indoles, or alcohols acting on cyclic O-Mannich bases. The deaminomethylation reaction is also prc.sent in. several equilibria afforded by aminomethyl derivatives of benzotriazole (sec 209, Chap. 1, C.6). 

Para-substiluted phenols with strongly hindering groups in the ortho positions (544 X, sec Fig. 184, below) arc used as effective inhibitors of radical chain reactions, according to requirement (a), above. They can be prepared by Mannich synthesis or by reaction of aminomethyl derivatives. The relationships between structure and antioxidant properties of this class of compounds have been thoroughly investigated. - ... 

Nuclear aminomethyl derivatives are obtained by the Mannich synthesis when phenols or napthols are reacted with secondary cyclic and acyclic a%l amines. p-HydroxydimethylbenzylamLne (m.p. 200°C) is obtained from dimethylamine, formaldehyde, and phenoP - . ... 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

The synthesis of the series of 2,4,5-amino-substituted derivatives of 1-phenoxy-anthraquinone (II) was accomplished by an exchange of chlorine or bromine atoms upon heating the corresponding 1-chloro- or 1-bromoanthraquinones in a phenol-phenoxide solution as well as by alkylation of 1-aminomethyl- or dimethylanthra-quinones using methyliodide.14... 

When the aminomethylating species is an X-aminomethyl reagent, a mechanism involving the hydrogen-bonded complex 54 is generally proposed for carbonyl, - - - phenolic, and other - - substrates. Alternatively, an Sn2 mechanism, involving attack by the carbanion derived from the substrate, has been hypothesized. - - - - ... 

In several deamination reactions, formation of the hydroxymethyl derivatives 243 (Fig. 90) is frequently reported instead of the expected unsaturated product. Thus, deamination of para-aminomethyl phenols (242, R = p-hydroxyphenyl) produces an intermediate methylenequinonc, which then evolves to hydroxymethyl phenol by reaction with water, - whereas deamination of aminome-thane sulfonates (242, R = SO Na) proceeds through an Sn2 attack by water on the zwit-terionie form of the Mannich base to yield the hydroxylated derivative. - "... 

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. 

Macromolecular phenol derivatives have been extensively studied, and the ami-nomethylation reaetion is performed even on crosslinked substrates."- Aminomethylation of lignin for the purpose of produeing complexing agents should also be included in this erouD of reactions, as it is likely to occur on the phenolic moieties abundantly... 

The process, which includes the simultaneous separation and synthesis of vitamin E (a-tocopherol) (F ig, 181), appears particularly interesting aminomethylation at the phenolic ring of type 489 compounds allows the separation from the aminomethylated material of any vitamin E that may be present and that is unable to undergo Mannich reaction. In a second step, further amounts of vitamin E are provided by hydrogenolysis of the aminomethylated product to the corresponding methyl derivative. ... 

Aminomcthylation of hctcroatoms (X-aminomcthylation in Table 6) is generally the easiest, whereas C-aminomethylation requires a great variety of experimental conditions. Indeed, the C—H moiety bound to a carboxyl group is among the less reactive systems, so that alkyl ketones require conditions A alkyl esters, which would be unstable under such conditions, have to be allowed to react with methyleneimmonium salts. Alkenes, as well as ferrocenyl derivatives, are also barely reactive. By contrast, the nitro group of nitroalkanes behaves as a very good activator of aminomcthylation, and phenols are readily aminomethylated. 

Homocydic aromatic substrates 214a-f (Table 16) include benzcnoid derivatives 214a-c, which arc mostly represented by phenols and give aminomethylation in the ortho or para position (Sec. C.2). Mannich reactions on the corresponding phcnolethers are much less frequent, and recent papers deal actually only with cyclizations (Sec. 

Phenolic Mannich bases afford cyclic derivatives as the result of deamination, O-heterocycles being prepared to a larger extent than N-heterocycles, although an interesting example of homocycle synthc.sis (Fig. 135) from para-aminomethylated phenolic Mannich bases is worth mentioning. ... 

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,... 

As with any molecule, a calixarene may be converted into chiral derivatives simply by attaching chiral substituents. In principle this can be done at the lower rim (at the phenolic oxygens) or at the upper rim (p-positions). Thus, compounds 1 and 2 were obtained by etherification of the corresponding calixarenes with 2-methylbutyl bromide or by Friedel-Crafts acylation with 2-methylbutanoyl chloride [1]. Aminomethylation with chiral amines like proline (3) may be mentioned as an example in the resorcarene series [2]. 

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