Di-cationic Ionic Liquid Catalyzed Synthesis of 1,5-Benzothiazepines

Abstract

A simple and elegant method for the synthesis of 1,5-benzothiazepines has been developed using di-cationic liquid as a solvent cum catalyst by the reaction of o-aminothiophenol with a variety of chalcones under mild reaction conditions. Furthermore the reusability of the catalyst has also been studied for three cycles. All the reactions are proposed to proceed through a 1,4-conjugate Michael addition followed by a cyclo-condensation reaction. [21][22][23]. In addition to this, the special properties of the ionic liquids have influenced the rate of chemical reactions such as elimination reactions where, the rate of the reaction in ionic liquids was observed to be faster than those carried out in conventional organic solvents [24]. Notably, multifunctional group dicationic ionic liquids have been reported to have a greater range of physical properties than traditional and singly charged ionic liquids. They are often more thermally stable, less volatility and are more flexible in tuning their physicochemical virtues [25,26]. Herein, we report an efficient synthesis of various 1,5-benzothiazepines using dicationic liquids as a catalyst and as well as solvent. EXPERIMENTALGeneral procedure: A mixture of o-aminothiophenol (1.2 mmol)/o-phenylenediamine (1 mmol), chalcone (1.0 mmol) and IL-C (0.2 mmol, 0.1 g per mmol of chalcone) was stirred at 80 °C for 80 min under nitrogen atmosphere. After completion of the reaction, which was monitored by TLC, the reaction mixture was diluted with water (10 mL) and extracted with diethyl ether (3 × 25 mL). The combined organic layer was separated and dried over anhydrous magnesium sulphate. The solvent was evaporated under reduced pressure and the residue was purified by crystallization in ethanol to afford the pure solid 1,5-benzothiazepines. The water present in the aqueous layer was subjected for distillation and the left over residue contains the pure ionic liquid, which could be recycled.

Antidepressant Activities of Synthesized Benzodiazepine Analogues in Mice

“…Yield; 72.09%, appearance: light yellow crystalline solid, solubility: ethanol, chloroform, Rf value: 0.54, melting point: 111–114 °C. 1H NMR (400 MHz, CDCl3): δ 15.28 (s, OH), 7.51–7.52 (m, 2H), 7.15–7.41 (m, 6H), 7.21 (td, J = 1.5 Hz, J = 8.3 Hz, 1H), 6.78–7.23 (m, 2H), 6.67 (dd, J = 1.3 Hz, J = 7.9 Hz, 1H), 6.92–6.79 (m, 1H), 5.32 (dd, J = 3.1 Hz, J = 8.0 Hz, 1H), 3.81 (bs, NH), 3.33 (dd, J = 3.7 Hz, J = 13.7 Hz,1H), 3.06 (dd, J = 8.7 Hz, J = 13.6 Hz, 1H) [ 20 ].…”

The green chemistry of chalcones: Valuable sources of privileged core structures for drug discovery

“…Sakirolla et al employed imidazolium salt ionic liquids to synthetize 1,5-benzothiazepine starting from α,β-unsaturated carbonyl systems typified by chalcones ( Figure 4D ). These ILs have proven to be environmentally friendly since they can be recycled for three cycles, IL-C is the most efficient reaction medium among the others because it allowed to reduce the time reaction and increase the final yield ( Sakirolla et al, 2018 ). Recently, the research group of Dhadda, has applied together with the use of ionic liquids with the technique of sonication and managed to create a scheme for different synthetic heterocyclic compounds, including 2-amino-3,4-pyrimidine, pyrazole, oxazole, and pyridine derivatives.…”

Chalcone derived benzoheterodiazepines for medicinal applications: A Two‐pot and one‐pot synthetic approach

“…Apart from acidic and basic condensation, ionic liquid-based condensation has also been reported to refine the reaction conditions and yield. Ionic liquids are thermally stable, environmentally friendly, non-volatile, and reusable 'green' solvents and catalysts for numerous chemical reactions [139]. Protic acidic ionic liquids (PAILs) have dual nature used as efficient acidic catalysts and solvents in organic reactions especially for the synthesis of 1,5-benzodiazepines (17 and 18) via condensation of α, β-unsaturated chalcones ( 16…”