One‐Pot Synthesis of Tetrahydropyridine Derivatives: Liquid Salt Catalyst vs Glycolic Acid Promoter. Structure and Antiradical Activity of the New Products

Abstract

Diethanolammonium hydrogensulfate (DHS), as a liquid salt, and glycolic acid (GA) were used for the synthesis of highly functionalized tetrahydropyridines (THPs). Due to the simplicity of the reaction procedure, excellent diastereoselectivity, and catalyst regeneration, these green protocols may be considered as an attractive approach for the preparation of THPs. Unlike numerous reported reactions for the synthesis of THPs that last for hours and with heating, GA‐promoted reactions finished mostly within an hour and at room temperature. As improvement to other organocatalysed reactions for the synthesis of THPs with moderate yields, this protocol provided good to excellent yields. Application of these procedures produced three vanillic compounds reported here for the first time. Their structure was elucidated based on experimental and theoretical data (IR, 1H NMR, 13C NMR, NOESY, UV‐Vis, and DFT). Experimental and theoretical antioxidant evaluation of these compounds has been carried out. DFT thermodynamical parameters supported experimental results that newly synthesized THPs deserve considerable attention as potent radical scavengers.

Acetophenone Mannich bases: study of ionic liquid catalysed synthesis and antioxidative potential of products

“…To determine the most probable mechanism of radical scavenging of MB8 and MB10 (hydrogen atom transfer (HAT), single electron—proton transfer (SET-PT) and sequential proton-loss electron-transfer (SPLET)), DFT was employed, homolytic/heterolytic dissociation of N–H bond was investigated. For estimation of the mechanism in the absence of free radicals, bond dissociation enthalpy (BDE), ionization potential (IP) and proton abstraction (PA) energies were calculated [13,54–60], while in the presence of free radicals, the reaction enthalpies (Δr H ) were calculated for the reactions of MB8 and MB10 with each of the eight selected free radicals. Details on terms upon which radical selection was made (hydroxy ( • OH), hydroperoxy ( • OOH), methylperoxy (CH 3 –O–O • ), superoxide radical anion (O 2 •− ), methoxy ( • OCH 3 ), tert -butoxy ( • OC(CH 3 ) 3 ), vinyl peroxy (CH 2 =CH–O–O • ) and DPPH), as well as details on the calculation of thermodynamic parameters in the absence and in the presence of free radicals are provided in our previous studies, and for the sake of clarity presented in the electronic supplementary material [13,61].…”

“…Acetophenone-derived Mannich bases ( MBs ) are very interesting and important compounds in medicinal chemistry and drug discovery, because they act as important pharmacophores with promising activity [5–11]. It turned out that their cytotoxic activities against T-lymphocyte (Jurkat), renal carcinoma (Renca) and mammary (EMT6) carcinoma cells lines were significant [12,13]. In addition, these compounds possess good antimicrobial [14–17], as well as anti-inflammatory activities [18].…”

“…Published by the Royal Society under the terms of the Creative chloroacetate [HDEA] [ClAc] as catalyst (20 mol%) and 1 ml of ethanol were placed in flask and stirred at room temperature for 24 h. When the reaction was completed, the solid product was separated by filtration and washed with ethanol. The MBs were obtained by recrystallization from chloroform and propanol 2 : 1 (v/v) and identified by 1 H NMR, 13 C NMR, IR spectroscopy, melting point and elemental analysis. Upon the evaporation of the solvent, the remaining catalyst was used in new experiments.…”

“…the yields were up to 5% lower. The characterizations of the new compounds are given in main part of the manuscript, while for known compounds in the electronic supplementary material, as well as 1 H and 13 C NMR spectra for all compounds.…”

Ultrasound-assisted aqua-mediated synthesis of multi-substituted tetrahydropyridine-3-carboxylates using N-carboxymethyl-3-pyridinium hydrogensulfate ([N-CH2CO2H-3-pic]+HSO4−) as a new efficient ionic liquid catalyst

“…Tetrahydropyridine (THP) moiety exists in various alkaloids and natural products [5]. Tetrahydropyridine existence in heterocycles cause to different pharmacological and biological activities such as antimicrobial activity against Escherichia coli [6], antimalarial [7], anti-oxidant (which made them as potent radical scavengers) [8], anti-fungicidal and insecticidal [9], anti-tumor [10], and neuroprotective (Parkinson's disease) [11]. Some compounds hold THP scaffolds also used as corrosion inhibitors for mild steel [12], Recently a wide range of functionalized tetrahydropyridine-3-carboxylates has been synthesized via the reaction of various aldehydes, amines, and β-keto esters utilizing various catalysts under different conditions such as: bromodimethylsulfonium bromide (BDMS) in acetonitrile at room temperature [13], FeCl 3 /SiO 2 NPs in refluxing methanol [14], Bi(III) immobilized on triazine magnetized dendrimer (Fe 3 O 4 @TDSN-Bi(III)) in ethanol at room temperature [15], nano-Al 2 O 3 /BF 3 /Fe 3 O 4 at 80 °C [16], CAN in Supplementary Information The online version contains supplementary material available at https:// doi.…”