Efficient Ultrasound-Assisted Green Synthesis of β-Enaminones Using Cost-Effective Coal Tar-Based POP: A Sustainable Approach with Molecular Docking Insights into Antibacterial Potential
M. Sadegh Ramezani, Sadegh Safaei, Mina Ardestani, Zahra Goodarzi, Mahan MirzaeianIntroduction:
A green, sustainable, and ultrasound-assisted method for the synthesis of β-enaminone derivatives was developed. This study introduces a sulfur-enriched coal tar-based porous organic polymer (CTHP-SES) as a highly efficient, metal-free catalyst, providing an environmentally friendly alternative to conventional synthetic methods.
Methods:
The synthesis employed CTHP-SES, a metal-free catalyst characterized by a microporous framework and thiol-functionalized acidic sites. Optimization studies were conducted to determine the optimal reaction conditions, including solvent selection and catalyst loading. Propylene carbonate was identified as the most suitable solvent, while 20 mg of catalyst afforded efficient conversion under mild, ultrasound-assisted conditions.
results:
Propylene carbonate was identified as the optimal solvent, with 20 mg of CTHP-SES catalyst achieving an 88% yield of the model β-enaminone in 20 minutes. The catalyst demonstrated broad substrate scope, efficiently converting a wide range of aromatic and aliphatic amines into β-enaminones with yields up to 93%. CTHP-SES exhibited superior activity and recyclability compared to conventional catalysts, retaining over 80% of its catalytic efficiency after six reuse cycles. In molecular docking, the synthesized β-enaminones showed strong binding affinities, with compound E-17 showing the highest binding affinity (-8.22 kcal.mol⁻¹) through hydrogen bonding with TRP229 and ARG222 residues.
Results:
The optimized protocol enabled the synthesis of β-enaminones in yields of up to 93% within only 20 minutes. The CTHP-SES catalyst exhibited a broad substrate scope, efficiently converting a wide range of aromatic and aliphatic amines. Notably, it outperformed conventional catalysts such as ZnCl₂, AlCl₃·6H₂O, FeCl₃, and p-TSA in terms of catalytic activity and recyclability, retaining more than 71% of its initial efficiency after seven reuse cycles.
Discussion:
The excellent catalytic performance of CTHP-SES is attributed to its acidic framework, which facilitates ketone activation. Its superior activity and reusability highlight its potential as a sustainable green catalyst. Molecular docking studies against the CTX-M-64 enzyme revealed strong antibacterial potential for the synthesized β-enaminones, with compound E-17 exhibiting the highest binding affinity (−8.22 kcal mol⁻¹), suggesting promising therapeutic applications.
Conclusion:
This study successfully established a sustainable and efficient ultrasound-assisted protocol for the synthesis of β-enaminones using the CTHP-SES catalyst. The synthesized β- enaminones demonstrated significant antibacterial potential, highlighting the dual applicability of this work in both catalysis and medicinal chemistry.