Synthesis of (E)-2-methoxy-6-(R-imino)methylphenols and 2-methoxy-6-(R-amino)methylphenols

Abstract

E)-2-Methoxy-6-(R-imino)methylphenols were synthesized by the condensation of 2-hydroxy-3-methoxybenzaldehyde with primary amines. By reduction of the iminophenols with sodium triacetoxyborohydride 2-methoxy-6-(R-amino)methylphenols were obtained.The necessity to control the newly emerging resistant pathogen strains stimulates permanently a research on the synthesis of new biocidal agents to update their range [1]. Using the ester and azomethine bonds as the mounting elements (linkers) for covalent attachment of different functional and pharmacophore groups to the aldehydes of the vanillin series may serve as an example of such molecular design [2]. Previously we reported on the synthesis of Schiff bases, the derivatives of 4-hydroxy-3-methoxy-(ethoxy)benzaldehydes with high biological activity [3,4].In this paper we describe the preparative method of the synthesis of hydroxy-containing Schiff bases III obtained by condensation of 2-hydroxy-3-methoxybenzaldehyde (ortho-vanillin) I with aliphatic, cycloaliphatic, and aromatic amines II in anhydrous methanol at the boiling point of the solvent. The yield of compounds III was 80-87%.We have studied reduction of hydroxyazomethines III with sodium triacetoxyborohydride Na[BH(OAc) 3 ] in ether at a temperature of 20-25°C. Reduction of azomethines III to the corresponding hydroxyamines IV is completed in 10-12 h. The yield of the hydroxyamines IV was almost quantitative, 92 to 94%. At the reduction, which was carried out in specially chosen mode of moderate temperature and acid exposure [5], there was no side reaction of reduction or hydrolysis of the side ester groups in the compounds IVd-IVg, IVy, IVz.