Naphthols Mannich reaction

The potential utility of the Mannich-type phenolic bases makes the aminoalkyla-tion reaction of naphthol derivatives a subject of current chemical interest. But, because of the relatively low reactivity of 1-naphthol, the reaction gave only a moderate yield and displayed moderate diastereoselectivity [5]. 

The case of diketonc 66 is more difficult to interpret, as this substrate undergoes a Mannich reaction initially on the acetyl group at position 4 of the 1-naphthol ring and is then further aminomethylated at the acetyl group in position 2. ... 

Okuda, T. and Maisumoto, U., Alkylation with Mannich bases. V. Mannich reaction of acyl-l-naphthols, YakugakuZasshi, 79, 1140, 1959 C/tem. Ahstr., 54.. 34.62, 1960. 

Fulop and co-workers [124] have reported the synthesis of some new (ami-noalkyl) naphthols and (aminoalkyl) quinolinols 85 in good yields through a one-pot, microwave-assisted three-component modified Mannich reaction of naphthol or quinolinol with two equivalents of an aldehyde using ammonium carbamate or ammonium hydrogen carbonate as solid ammonia sources. It was observed that aliphatic aldehydes did not lead to the formation of the desired (aminoalkyl) quinolinols 85 (Scheme 64). 

Keywords S-naphthol, benzaldehyde, piperidine, Mannich reaction, acidic alumina, aminoalkylation, microwave irradiation... 

In the early 1900s, the distinguished Italian chemist Mario Betti demonstrated that 2-naphthol (1) can be a good carbon nucleophile toward imine 3, produced from benzaldehyde and aniline. Although the Betti reaction is mechanistically related to the Mannich reaction, Betti s work preceded the development of this more widely known reaction. ... 

Although detailed mechanistic studies on the Betti reaction have not been carried out, it is widely assumed the reaction follows a similar course to the Mannich reaction. This principally involves the condensation of the aldehyde and amine constituents to form the active iminium electrophile 7. 2-Naphthol (1) functions as a nucleophile, giving the intermediate represented by the resonance structures 8 and 9, which subsequently loses a proton to yield the product. It is easy to appreciate from this mechanism why acid catalysis may facilitate the reaction, and indeed increased rates have been observed using such catalysis. ... 

A survey has appeared of the reactivity of 2,6-disubstituted phenols and 2-methyl-l-naphthol with A -methoxymethylmonoaza-12-crown-4 ether in the Mannich reaction. The acidity and the electrostatic charge of the aromatic compounds are indicators of their reactivity. Compound (20) was formed from the above naphthol in this reaction. In the presence of aluminium chloride, chlorothiophenes react with activated aromatic compounds to form arylthiophenes. The aluminium chloride-catalysed selfcondensation of chlorothiophenes produces mainly bi- and ter-thiophenes. 

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