A fast, mild, and efficient catalyst-free approach has been developed for the synthesis
of chromonyl-substituted alpha-aminophosphine oxides by the three-component reaction
of 3-formyl-6-methylchromone, primary amines, and secondary phosphine oxides at ambient
temperature. Carrying out the reaction with aliphatic amines or aminoalcohols at a
higher temperature (80 degrees C), phosphinoyl-functionalized 3-aminomethylene chromanones
were formed instead of the corresponding chromonyl-substituted alpha-aminophosphine
oxides. No reaction occurred when 3-formyl-6-methylchromone and secondary phosphine
oxides were reacted with aromatic amines in the absence of any catalyst. Applying
a basic catalyst, the formation of the phosphinoyl-functionalized 3-aminomethylene
chromanones was observed; however, the reaction was not complete. Detailed experimental
and quantum chemical studies were performed to study the transformation. Moreover,
the in vitro cytotoxicity of phosphinoyl-functionalized 3-aminomethylene chromanones
was also investigated in three different cell lines, such as human lung adenocarcinoma
(A549), mouse fibroblast (NIH/3T3), and human promyelocytic leukemia (HL60) cells.
Several derivatives showed modest activity against the human promyelocytic leukemia
(HL60) cell line.
