Three-component synthesis, utilization and biological activity of phosphinoyl-functionalized isoindolinones

Abstract

A new method for the synthesis of 3-oxoisoindolin-1-ylphosphine oxides bearing same or different substituents on the phosphorus atom is described. The one-pot three-component reaction of 2-formylbenzoic acid, primary amines and...

Multicomponent Synthesis of Potentially Biologically Active Heterocycles Containing a Phosphonate or a Phosphine Oxide Moiety

“…[54][55][56][57][58][59][60][61] In our research work, the three-component condensation of FBA, butyl-, cyclohexyl-, benzylamine or aniline and diphenylphosphine oxide was studied. 62 An efficient method was elaborated by us, where complete conversion was obtained in the absence of any catalyst, at room temperature, after short reaction times (10-20 min) in acetonitrile. The condensation was extended to various secondary phosphine oxides, such as bis(p-tolyl)-, bis(3,5-dimethylphenyl)-, bis(2-naphthyl)-or dibenzylphosphine oxides (Scheme 2).…”

“…Among (3-oxo-2,3-dihydro-2H-isoindol-1-yl)phosphine oxides 23-34, derivatives containing 3,5-dimethylphenyl-or naphthyl groups on the phosphorus atom showed activity. 62 The N-butyl and N-benzyl bis(3,5-dimethylphenyl)…”

Phosphoryl- or phosphinoyl-functionalized benzo[de]isoquinolinones: synthesis, experimental design, mechanism and biological activity

“…In these cases, an increased temperature of 60 °C in a MW reactor was necessary to form the corresponding benzo[de]isoquinolin-1-one-3-phosphine oxides (18)(19)(20) in good yields. Finally, the three-component reaction of 1,8-naphthalaldehydic acid with the secondary phosphine oxides mentioned above was also carried out using a chiral primary amine, DL-1-phenylethylamine.…”

“…Finally, the in vitro cytotoxicity on the MV-411 cell line was investigated, and it was found that all of the compounds showed moderate or good activity against these cells. The most active compounds were bis(3,5-dimethylphenyl) (2-benzyl-3-oxo-2,3-dihydro-1H-benzo[de]isoquinolin-1-yl)phosphine oxide (17) and bis(p-tolyl)-( 19) as well as bis(3,5-dimethylphenyl) [2-(3dimethylamino-propyl)-3-oxo-2,3-dihydro-1H-benzo[de]isoquinolin-1-yl)phosphine oxide (20).…”

“…18 In our preliminary studies, we have described the special catalyst-free Kabachnik-Fields reaction followed by cyclization as a suitable synthetic route for the ring closure of compounds bearing aldehyde and carboxylic groups with primary amines and >P(O)H reagents. 19,20 Based on these experiences, in this paper, we described the first method for the synthesis of benzo[de]isoquinolin-1one-3-phosphonates and phosphine oxidesas a new family of benzo[de]isoquinolin-1-onesby the propylphosphonic anhydride (T 3 P®)-mediated three-component reaction of 1,8-naphthalaldehydic acid, primary amines and dialkyl phosphites or secondary phosphine oxides [Scheme 1, eqn (4)]. T 3 P®, a process-friendly commercial compound, generally acts as an acidic and dehydrating agent in many organic syntheses known in the literature.…”