Aminomethylated Hydroxinaphthalenes: Synthesis and Application

The analysis of the literature is carried out and the results of the synthetic approaches to the aminomethylation of hydroxy derivatives of naphthalenes developed over the past 20 years are presented. Most of the described aminomethylation processes proceed as Mannich aminomethylation or, as a special case of a similar condensation --- aminobenzylation according to Betti. The results of all studies are grouped according to the nature of the amine used in the synthesis: primary, secondary, tertiary. Most of the examples were considered for 2-naphthol, however, as the analysis of literature data shows, similar methods are applicable to 1-naphthol and dihydroxynaphthalenes with different positions of OH groups in the ring --- often only the yields of the target product differ. Both the classical methods for the preparation of Mannich and Betti bases using the carbonyl component (formaldehyde, benzaldehyde and its derivatives, respectively) and special cases of synthesis, in which condensation is carried out by means of halogen derivatives, substituted azacrown ethers, etc., are presented. Particular attention is paid to the use of various catalysts and activators, allowing to significantly simplify the synthetic procedures and increase the yields of target compounds. The main fields of application of aminomethylated derivatives of hydroxynaphthalenes are presented

Synthesis and transformation of 6-aminomethyl derivatives of 7-hydroxy-2'-fluoroisoflavones

Mannich aminomethylation of 8-methyl-7-hydroxy-2'-fluoroisoflavones applying bis-(N,N-dimethylamino)methane afforded C-6 substituted N,N-dimethylaminomethyl derivatives. Subsequent acetylation of these compounds in acetic anhydride in the presence of potassium acetate provided access to the corresponding acetoxymethyl derivatives that were converted to hydroxymethyl- and alkoxymethyl-substituted 7-hydroxyisoflavonoids. Addition of 3-(N,N-dimethylamino)-5,5-dimethyl-2-cyclohexen-1-one or 1,3-dimethyl-5-aminopyrazole with thermally generated ortho-quinone methides led to hetero-Diels–Alder or Michael adducts.

Synthesis of aminomethyl derivatives of 5-substituted-3-(prop-2-ynyl)dihydrofuran-2(3H)-ones

An easy approach for the synthesis of various 5-substituted-3-(prop-2-ynyl)dihydrofuran-2(3H)-ones is described. As a method of choice, Mannich aminomethylation of terminal alkynes is adopted. The reaction works well with acyclic and cyclic secondary amines and provides the desired products, with good to very good yields.