A novel dual three and five-component reactions between dimedone, aryl aldehydes, and 1-naphthylamine: synthesis and computational studies

A series of one-pot, atom-economic, in parallel three and five-component reactions for the synthesis of acridine and bis(2-benzyl-5,5-dimethylcyclohexane-1,3-dione)-N-and 4-disubstituted naphthylamine derivatives under green conditions from the reaction between dimedone, aryl aldehydes, and 1naphthylamine have been investigated. The three-component route to the synthesis of acridine derivatives is well-known, but the five component route results in bis(2-benzyl-5,5-dimethylcyclohexane-1,3 dione)-N-and 4-disubstituted naphthylamine derivatives, which is an unprecedented pathway and is reported herein for the first time. By this achievement, a broad range of novel acridine and bis(2-benzyl 5,5-dimethylcyclohexane-1,3-dione)-N-and 4-disubstituted naphthylamine derivatives have been synthesized with substantial scores during in silico analyses, including molecular docking, molecular dynamics, and ADMET prediction tools. Acridine derivatives and N,4-disubstituted naphthylamines appear to interact significantly with 5-HT2A/C and MAO-A/B, respectively.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

A series of one-pot, atom-economic, parallel three and five-component reactions have been investigated for the synthesis of acridine and bis(2-benzyl-5,5-dimethylcyclohexane-1,3-dione)-N-and 4-disubstituted naphthylamine derivatives under green conditions. The five-component route resulted in unprecedented bis(2-benzyl-5,5-dimethylcyclohexane-1,3-dione)-N-and 4-disubstituted naphthylamine derivatives. The synthesized compounds showed significant scores in in silico analyses, including molecular docking, molecular dynamics, and ADMET prediction tools. Acridine derivatives and N,4-disubstituted naphthylamines exhibited significant interactions with 5-HT2A/C and MAO-A/B, respectively.