Novel synthesis of 2-naphthol Mannich bases and their NMR behaviour

Abstract

A novel two-step procedure involving the formation of 1-arylidene-2-tetralones from 2-tetralone and subsequent Michael addition of a cyclic secondary amine on the alkenone followed by in situ aerial oxidation was developed to produce 2-naphthol Mannich bases. A simple microwave-assisted one-pot synthesis of 2-naphthol Mannich bases was also carried out under solvent-free conditions from 2-naphthol and corresponding aldehydes and amines in the presence of p-toluenesulfonic acid. The compounds of this series displayed interesting NMR behaviour. Extensive variabletemperature NMR investigations, including HSQC experiments, are herein reported. NMR results on the conformation in solution phase were found to be consistent with the X-ray crystal structure in the solid state.Résumé : On a mis au point une nouvelle méthode en deux étapes qui permet de produire des bases de Mannich du 2-naphtol et qui implique la formation de 1-arylidène-2-tétralones à partir de la 2-tétralone, puis une addition subséquente de Michael d'une amine secondaire cyclique sur l'alcénone, suivie d'une oxydation in situ par de l'air. On a aussi réa-lisé une synthèse des bases de Mannich du 2-naphtol par une simple réaction monotope du 2-naphtol, des aldéhydes et des amines correspondants en présence d'acide p-toluènesulfonique, sous l'effet de micro-ondes, dans des conditions sans solvant. Les composés de cette série présentent des comportements RMN intéressants. On a effectué de nombreuses études RMN à température variable, y compris des expériences de « HSQC ». On a trouvé que les résultats de la RMN sur la conformation en solution sont en accord avec la structure cristalline déterminée par diffraction des rayons X, à l'état solide.Mots clés : bases de Mannich, réaction de Mannich assistée par les micro-ondes, spectroscopie RMN à température variable, dynamique RMN, cristallographie par diffraction des rayons X.[Traduit par la Rédaction] Jha et al. 853

Microwave-assisted synthesis of novel 2-naphthol bis-Mannich bases

“…[34][35][36] Our previous endeavour which led to formation of simple Mannich bases of 2-naphthol under solvent-free conditions involved the use of a conventional kitchen microwave and pTSA as catalyst. 26,27 As evident from data presented in Table 1, we were able to obtain bisMannich bases 1a-l in good to excellent yields in absence of any catalyst using neat conditions under microwave irradiation; conventional reflux reactions in ethanol benefitted from the use of pTSA (Table 1, entry 1a). The comparison of isolated yields, reaction time and material requirements of the two conditions employed showed microwave-assisted solvent-free reactions as the most efficient synthetic method in terms of energy and time consumption.…”

“…This led us to speculate that the compounds were crystallizing in a new crystal lattice, exhibiting polymorphism. The precipitation of the compounds after prolonged standing also caused difficulty in recording 13 C NMR spectra where molecular dynamics 27 was already causing disappearance of some peaks at room temperature (vide infra); the problem was compounded by frequent appearance of two peaks for some of the carbons since the products were diastereomeric mixtures. In 1 H-NMR, all compounds clearly showed strong hydrogen-bonding between phenolic H and neighboring N. However, peak broadening was causing ambiguity in the peak assignment.…”

“…Both 1 H and 13 C NMR spectra of compounds suffered from peak broadening owing to molecular dynamics characteristic of cyclic amines. 27 To improve the resolution of the NMR spectra, variable temperature NMR experiments were conducted on compound 1b (Figures 2-4). …”

Synthesis, Structure and Antimicrobial Studies of the Mannich Base N-(Dicyclohexylamino) (Phenyl) Methyl benzamide and its Metal Complexes

“…The widespread use of Mannich base metal complexes in biological field lies in the fact that the synthesis of Mannich base ligand introduces the basic future which can provide a molecule soluble in aqueous solvents and they can easily be transformed into a number of compounds. Many research articles are available in the literature for the synthesis of Mannich bases using indole 13,14 , benzaldehyde and substituted benzaldehydes 15 . In view of all these, it has been decided to synthesize a new Mannich base by the condensation of benzaldehyde, benzamide and dicyclohexylamine.The so synthesized base is made to undergo complexation with first row transition metals.The characterization of the ligand as well as the metal complexes were done by various physico-chemical and spectral methods.They are all tested for their antimicrobial activity against certain selected bacterial species and the results are discussed in this article…”

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“…The first synthesis of racemic Mannich-bases of 2-naphthol was achieved by Betti at the turn of the twentieth century. 4 Thereafter numerous modifications of this reaction surfaced [5][6][7][8][9][10] . Since these compounds have multiple centers for chelation with metal ions, they are likely to be potent inhibitors of metallo-enzymes 11,12 .…”