Continuous flow synthesis, characterisation and antioxidant activity of imine and secondary amine derivatives

Herein, we report a series of novel imines and secondary amines synthesized from 2,4,6-trimethylaniline and benzaldehyde derivatives using continuous flow technology coupled with in-line IR monitoring. In the imine synthesis, 95% conversion in approximately 5 minutes at 45 °C was achieved for the reaction between benzaldehyde and 2,4,6-trimethylaniline. A library of 19 novel imines were thereafter successfully generated under flow reaction conditions in 43-92% conversion. The methodology established was then used for the telescoped continuous flow synthesis of 19 secondary amines via reductive amination with a total residence time of 45 min in 31-94% conversion. The in silico ADMET profile for the imines and secondary amines calculated using SwissADME and pkCSM-pharmacokinetics web tools was acceptable for most of the compounds within Lipinski's and Verber's rules. Upon evaluation of antioxidant activity of these compounds using the DPPH free radical scavenging assay, the imine compounds were found to have moderate antioxidant activity (31-55%) compared to the secondary amines, which had low activity (23-39%). Molecular docking studies also elucidated that all synthesised compounds showed binding interactions to human antioxidant enzyme receptor 3MNG with a docking score range of -3.623 to -2.207 kcal mol^-1 for the imines and -3.966 to -2.716 kcal mol^-1 for the amines.