124104-99-0Relevant academic research and scientific papers
Microwave-Assisted Aminoalkylation of Phenols via Mustard Carbonate Analogues
Annatelli, Mattia,Aricò, Fabio,Castellano, Sabrina,Milite, Ciro,Trapasso, Giacomo,Viviano, Monica
supporting information, (2022/03/17)
microwave-assisted chlorine-free direct phenol substitution is presented, which is indicated as a key green chemistry research area for pharmaceuticals manufacturers. The reaction of -aminocarbonates (mustard carbonates) with several substituted phenols in the presence of a polar solvent (acetonitrile or butanol) led to the related aminoalkylated products via the anchimeric assistance of the nitrogen incorporated in the organic carbonate backbone. The aminoalkylation required short reaction time (7 min) and the related products were isolated in high yields (>90%) via quick liquid-liquid extraction or column chromatography depending on the solvent employed. Furthermore, microwave irradiation also promoted the one-pot aminoalkylation of phenol in excellent yield. In this approach a -aminoalcohol was reacted with phenol in the presence of diethyl carbonate, used for the in situ formation -aminocarbonate, key intermediate in the consequent anchimerically driven alkylation. The resulting product, namely N,N-dimethyl- 2-phenoxyethanamine, was isolated as pure in almost quantitative yield.
Mustard Carbonate Analogues as Sustainable Reagents for the Aminoalkylation of Phenols
Annatelli, Mattia,Trapasso, Giacomo,Salaris, Claudio,Salata, Cristiano,Castellano, Sabrina,Aricò, Fabio
supporting information, p. 3459 - 3464 (2021/05/24)
N,N-dialkyl ethylamine moiety can be found in numerous scaffolds of macromolecules, catalysts, and especially pharmaceuticals. Common synthetic procedures for its incorporation in a substrate relies on the use of a nitrogen mustard gas or on multistep syntheses featuring chlorine hazardous/toxic chemistry. Reported herein is a one-pot synthetic approach for the easy introduction of aminoalkyl chain into different phenolic substrates through dialkyl carbonate (β-aminocarbonate) chemistry. This new direct alcohol substitution avoids the use of chlorine chemistry, and it is efficient on numerous pharmacophore scaffolds with good to quantitative yield. The cytotoxicity via MTT of the β-aminocarbonate, key intermediate of this synthetic approach, was also evaluated and compared with its alcohol precursor.
