# Thiamine hydrochloride (VB1) in aqueous media catalyzed the synthesis of polysubstituted quinolines via a one-pot strategy: a combined experimental and theoretical investigation

## TL;DR

This study shows how thiamine hydrochloride in water can efficiently synthesize complex quinoline compounds in one step, with high yields and catalyst reusability.

## Contribution

A novel one-pot method using thiamine hydrochloride in water for synthesizing polysubstituted quinolines, supported by DFT calculations.

## Key findings

- Thiamine hydrochloride catalyzed the synthesis of 4-amino-2-benzoylquinoline-3-carboxamide in water with high yields.
- Solvent stability calculations showed water to be the most effective medium for the reaction.
- Electronic properties of the compounds were estimated and correlated with solvent effects.

## Abstract

In this work, an efficient one-pot three-component reaction of 2-cyano-N-methylacetamide, arylglyoxals, and arylamines in the presence of thiamine hydrochloride in H2O under reflux conditions was designed for the synthesis of 4-amino-2-benzoylquinoline-3-carboxamide. In this protocol, various synthetic methods such as Knoevenagel/Michael/cyclization cascade reactions were used to introduce different functional groups, such as amino and carboxamide groups, on the quinoline ring system in a single step. In addition to operational simplicity and absence of tedious separation procedures, this method offered the advantages of catalyst reusability and high product yields. Characterization techniques such as nuclear magnetic resonance spectroscopy, infrared spectroscopy, and CHN analysis were used to confirm the structure and purity of the synthesized compounds. In addition to the experimental results, the influence of solvent on the stability of compounds was investigated using DFT calculations at the B3LYP/6-311++G(d,p) level. Compared with solvent-free conditions, the stability of compounds was amplified in the presence of solvents and increased in the order of H2O > DMF > CH3CN > EtOH > THF. This trend was also in agreement with the experimental results. Theoretical data confirmed that the reaction performed best in water medium. Moreover, some electronic properties of these compounds, such as band gap, first ionization energy, electron affinity, electronic chemical potential, electrophilicity index, hardness and softness, were theoretically estimated in the presence of various solvents.

A combined experimental and theoretical investigation on the synthesis of polysubstituted quinolines in the presence of VB1 in aqueous media.