Thioamide Derivatives Research Articles

Convenient Synthesis of Pyrano[3,2‐g]chromene‐6‐ones from Naturally Occurring Visnagin and Evaluation of their Antimicrobial Activity

AbstractIt is well known that chromones possess numerous of biological activities. Due to their significant applications, there are increasing for synthesizing of several chromones but few pyranochromene have been synthesized. So, simple and convenient routes for the synthesizing of new pyrano[3,2‐g]chromenone derivatives in high yields were illustrated using visnagin as starting naturally occurring. Ring opening of visnagin afforded 6‐formyl‐7‐hydroxychromone derivative which was subjected to react with variety of active methlyene derivatives to afford pyrano[3,2‐g]chromenone derivatives. Thus, heating of 6‐formylchromone with aroylacetate gave the 3‐(aroyl)‐pyranochromene‐2,6‐dione. The desired pyranochromene‐3‐carboxamide derivatives were obtained when the precursor 6‐formylchromone was condensed with ethyl 3‐oxo‐3‐(arylamino)propanoates. When 6‐formylchromone was condensed with hippuric acid gave oxazolone derivative rather than pyranochromene derivative. Condensation of 6‐formylchromone with cyanothioacetamide led to the formation of thioamide derivative. 2‐Iminopyranochromene derivatives were synthesized through reaction of 6‐formylchromone with diverse cyanoacetamide derivatives. Finally, reaction of 6‐formylchromone with 3‐(dimethylpyrazolyl)‐3‐oxopropanenitrile gave 3‐cyano‐pyranochromenedione rather than pyrazole derivative. Antimicrobial activity of the synthesized pyranochromenone derivatives was evaluated. Nearly all compounds showed weak effects towards B. subtilis and P. vulgaris. All compounds showed no effects towards S. aureus and E. coli. All compounds showed no effects towards all tested fungi except thioamide derivative 6 showed moderate activity.

Photoinduced dual bond rotation of a nitrogen-containing system realized by chalcogen substitution.

Photoinduced concerted multiple-bond rotation has been proposed in some biological systems. However, the observation of such phenomena in synthetic systems, in other words, the synthesis of molecules that undergo photoinduced multiple-bond rotation upon photoirradiation, has been a challenge in the photochemistry field. Here we describe a chalcogen-substituted benzamide system that exhibits photoinduced dual bond rotation in heteroatom-containing bonds. Introduction of the chalcogen substituent into a sterically hindered benzamide system provides sufficient kinetic stability and photosensitivity to enable the photoinduced concerted rotation. The presence of two different substituents on the phenyl ring in the thioamide derivative enables the generation of a pair of enantiomers and E/Z isomers. Using these four stereoisomers as indicators of which bonds are rotated, we monitor the photoinduced C-N/C-C concerted bond rotation in the thioamide derivative depending on external stimuli such as temperature and photoirradiation. Theoretical calculations provide insight on the mechanism of this selective photoinduced C-N/C-C concerted rotation.

Green synthesis of thioamide derivatives in an environmentally benign deep eutectic solvent (DES)

A wide variety of thioamides are obtained in good-to-excellent yields by the reaction of substituted aldehydes/ketones, secondary amines, and elemental sulfur in a choline chloride–urea (1 : 2)-based deep eutectic solvent (DES).

Polymer-supported thioamide-derived cinchona alkaloids as efficient organocatalysts for the enantioselective decarboxylative protonation

A new family of copolymers based on styrene and a polymerizable cinchonidine thioamide derivative was synthesized by conventional radical polymerization. The copolymers were tested as homogeneous supported organocatalysts in the enantioselective decarboxylative protonation (EDP) of α-aminomalonate hemiesters giving access to α-amino acids under very mild conditions. These macromolecular catalysts could be prepared on a large scale and outperformed their unsupported analogues providing the desired products in high yield and enantioselectivity. Furthermore, recycling experiments were conducted which showed good enantioselectivities.

Surface Modification in CsPb0.5Sn0.5I2Br Inorganic Perovskite Solar Cells: Effects of Bifunctional Dipolar Molecules on Photovoltaic Performance.

Inorganic tin-lead binary perovskites have piqued the interest of researchers as effective absorbers for thermally stable solar cells. However, the nonradiative recombination originating from the surface undercoordinated Sn2+ cations and the energetic offsets between different layers cause an excessive energy loss and deteriorate the perovskite device's performance. In this study, we investigated two thioamide derivatives that differ only in the polar part connected to their common benzene ring, namely, benzenecarbothioamide and 4-fluorophenylcarbothioamide (F-TBA). These two molecules were implemented as modifiers onto the inorganic tin-lead perovskite (CsPb0.5Sn0.5I2Br) surface in the perovskite solar cells. Modifiers that carry C═S and NH2 functional groups, equipped with lone electron pairs, can autonomously associate with surface Sn2+ through coordination and electrostatic attraction mechanisms. This interaction serves effectively to passivate the surface. In addition, due to the permanent dipole moment of the intermediate layer, an interfacial dipole field appears at the PCBM/CsPb0.5Sn0.5I2Br interface, reducing the electron extraction potential barrier. Consequently, the planar solar cell with an ITO/PEDOT:PSS/CsPb0.5Sn0.5I2Br/PCBM/BCP/Ag layered structure featuring an F-TBA surface post-treatment demonstrated a noteworthy power conversion efficiency of 14.01%. Simultaneously, after being stored for 1000 h in an inert atmosphere glovebox, the non-encapsulated CsPb0.5Sn0.5I2Br solar cells managed to preserve 94% of their original efficiency.

Synthesis and Evaluation of Thioamide and Bromo Derivatives of 1,3-Diphenylpropane-1,3-dione as 5α-Reductase Inhibitors.

1,3-Diphenylpropane-1,3-dione (1) is an acetylacetone β-diketone in which both of the methyl groups have been replaced with phenyl groups. It is a component of licorice root extract (Glycyrrhiza glabra) and has anti-mutagenic and anti-cancer properties. It functions as a metabolite, an anti-mutagen, and an anti-neoplastic agent. It is an aromatic ketone and a β-diketone. 1,3-Diphenylpropane-1,3-dione (1) is primarily used in PVC hard and soft materials, including plates, films, profiles, pipes, and fittings. This research aims to examine the utility of 1,3-diphenylpropane-1,3-dione (1) for the synthesis of a variety of new heterocyclic compounds, such as thioamide, thiazolidine, thiophene-2-carbonitrile, phenylthiazole, thiadiazole-2-carboxylate, 1,3,4-thiadiazole derivatives, 2-bromo-1,3-diphenylpropane-1,3-dione, new substituted benzo[1,4]thiazines, phenylquinoxalines, and imidazo[1,2-b][1,2,4]triazole derivatives of potential biological activity Methods: 1,3-Diphenylpropane-1,3-dione (1) was used as a starting compound for the synthesis of 3-oxo-N,3-diphenyl-2-(phenylcarbonyl)propanethioamide (3) and 2-bromo-1,3-diphenylpropane-1,3-dione (25), which can be used for further preparations. The 5α-reductase inhibitor activity of some of the synthesized compounds was also tested in vivo; the ED50 and LD50 data were established, Results: Using IR, 1H-NMR, mass spectroscopy, and elemental analysis, the structures of all produced compounds were elucidated. Some of these prepared compounds were reported as 5α-reductase inhibitors. New heterocyclic compounds can be formed via 1,3-diphenylpropane-1,3-dione (1), and some of these compounds can act as 5α-reductase inhibitors.

Direct Radical Copolymerizations of Thioamides To Generate Vinyl Polymers with Degradable Thioether Bonds in the Backbones

Direct radical addition reactions of thiocarbonyl (C═S) groups unaccompanied by β-scission have rarely been reported despite their potential for constructing various sulfur-containing compounds. Herein, we report direct radical copolymerizations of the C═S double bonds of simple thioamide derivatives and the C═C double bonds of common vinyl monomers to produce novel degradable vinyl polymers that contain thioether units in the backbones. In particular, N-acylated thioformamides copolymerized smoothly with various vinyl monomers, such as methyl acrylate, vinyl acetate, N,N-dimethylacrylamide, and styrene. RAFT copolymerization was also successfully mediated. The resultant copolymers had high glass transition temperatures and were readily degradable under ambient conditions. This work will expand the potential for use of thiocarbonyl compounds in radical reactions and develop novel poly(thioether)-vinyl polymer hybrid materials with unusual properties.

TfOH-Catalyzed Regioselective S–H Insertion of Cyclic Thioamide Derivatives with Diazo Compounds at Room Temperature

We have developed a method for highly regioselective S-H bond insertion reactions of various diazo compounds and cyclic thioamide derivatives at room temperature. These reactions provide straightforward access to alkylated benzimidazoles, benzothiazoles, and benzoxazoles. This mild method uses readily available TfOH as a catalyst and features a broad substrate scope, good functional group tolerance, good to excellent yields, and high regioselectivities.

Synthesis of novel thiazole, imidazole, benzimidazole, and benzothiazole derivatives incorporating 2‐phenoxy‐N‐arylacetamide unit as novel hybrid molecules

AbstractNovel 2‐phenoxy‐N‐phenylacetamide hybrids with heterocyclic scaffolds such as thiazoles, imidazoles, benzimidazoles, and benzothiazoles were synthesized efficiently in this study. The reaction of the appropriate α‐haloketone with the corresponding thioamide derivatives in EtOH/DMF at reflux in the presence of a few drops of TEA produced good yields of 2‐aryl‐ or heteroarylthiazoles. A one‐pot three‐component reaction of 1,2‐diketone with aldehydes and ammonium acetate in methanol at reflux yielded imidazole derivatives. It was also feasible to synthesize benzimidazoles, benzothiazoles, or imidazo[4,5‐b]pyridines by employing the reactions of the appropriate aldehydes with o‐phenylenediamine, 2‐aminothiophenol, or 2,3‐diaminopyridine, respectively, in ethanol at reflux in the presence of NaHSO3. The new compounds' structures were validated using spectrum data and elemental analyses.

Modulation of inflammatory mediators involved in the antinociceptive and anti-inflammatory effects of a new thioamide derivative: thiocyanoacetamide.

Inflammatory pain is part of the body's defense mechanism and plays an important role in the healing process. Although some drugs are efficient and intensively used for their potent anti-inflammatory properties, they present problematic side effects. The aim of this study was to evaluate the anti-nociceptive effect of the thiocyanoacetamide (Thm) compared to paracetamol (Para), dexamethasone (Dex) and morphine (Morph) and to study inflammatory mediators on models of acute inflammatory pain in rats using the formalin injection test in the hind paw of rats as chemical stimulus. The obtained results showed significant modulation of pain by Thm pretreatment with a maximum at an effective dose (10mg/kg) proved by the absence of lickingand biting of the affected paw during the early and late phases of inflammation. This effect was comparable to Dex at 10mg/kg, Para at 400mg/kg and less than Morph at 5mg/kg pretreatment doses. The study of anti-inflammatory targets showed that Thm pretreatment maintained plasma serotonin release at normal level compared to the negative control group (T-) and corrected the decrease in the plasma level of prostaglandins after inflammatory induction with no variation in the level of histamine in different groups. The evaluation of inflammation mediators demonstrated that the pretreatment with Thm induced the decrease in the amount of both IL-1 Beta and TNF alpha in plasma and the increase in their amount in the tissue of the injection site. The Thm has been promoted as an anti-nociceptive drug that induces modulation of inflammatory mediators.

Synthesis and antioxidant activity evaluation of some new 4-thiomethyl functionalised 1,3-thiazoles

The 4-bromomethyl-substituted thiazolium salts and corresponding thiazoles obtained through the condensation of 1,3-dibromoacetone with thioamide derivatives were utilised as efficient alkylating reagents for a series of thiophenols and heterylthiols. As a result, a small library of 4-thiomethyl-functionalised 1,3-thiazoles was synthesised in high yields, and their structures were characterised by 1H, 13C NMR, LC-MS and IR spectra. Antioxidant activity of obtained compounds was studied in vitro using the DPPH test. The synthesised compounds showed high absorption level of DPPH radicals in the 70-98% range. For the most active derivatives 7e,m,p,t IC50 values were determined, which were in the range 191-417 µM (for ascorbic acid (reference) IC50 value was 29 µM). Obtained radical scavenging activity screening data suggest in-depth study of the antioxidant potential for these types of heterocyclic compounds.

Catalyst‐ and Solvent‐Free Thioamidation of Aromatic Aldehydes through a Willgerodt‐Kindler Reaction

AbstractA simple, straightforward, and highly efficient approach has been developed to synthesize thioamide derivatives under catalyst‐ and solvent‐free conditions at 100 °C/room temperature. Total 51 thioamides were synthesized via a one‐pot multicomponent Willgerodt‐Kindler reaction between substituted aromatic aldehydes, elemental sulfur powder and amines with 70–98 % yield within 20–70 min using cyclic secondary amines and 1.5–24 h using aliphatic primary and secondary amines. The cyclic secondary amines react faster than aliphatic amines. Twenty‐one newer compounds were prepared and characterized by 1H NMR, 13C NMR, HRMS. Mild reaction conditions, good yields, and a wide range of reactions demonstrate the excellent synthetic utility of this method. The developed protocol showed that there is no need to collect, purify, recycle, and remove the solvent after the reaction is complete. Reaction rates are generally high due to the high availability of reactants, i. e., shortens the reaction time, is environmentally friendly, and which makes the overall process more sustainable and economical.

Thioamide synthesis via copper-catalyzed C–H activation of 1,2,3-thiadiazoles enabled by slow release and capture of thioketenes

A copper-catalyzed coupling of 1,2,3-thiadiazoles with various amines under base-free conditions was developed as a robust protocol for the synthesis of thioamide derivatives via C–H activation/Cu coordination strategy.

Preparation and evaluation of some eco-friendly olethio-amide derivatives as lube oil additives

Eco-friendly synthesis of organic compounds is a major trend in green chemistry. Thus, we aim at producing some of the lube oil additives through the use of green chemistry. Dispersant lube oil additives are remarkable additives that regulate the formation of deposits throughout the process. Antioxidants do not prevent the oxidation reactions but only delay the rate of this process. In the present work, some additives for lube oil based on thiourea derivative were prepared by one-step reaction, which is the reaction of octadeca-7-enoy) chloride with ammonium thiocyanate in addition to different amines such as ethylenediamine, diethylene triamine, and tetraethylene pentamine as three-component system in order to prepare thioamide derivatives (A, B, and C). Infrared spectroscopy, elemental analysis, nuclear magnetic resonance, determination of molecular weights, and yield determination verified the chemical structure of all synthesized molecules. All the compounds produced are tested as lube oil additives (dispersants and antioxidants), and it has been found that all the compounds prepared are good as dispersants but have poor effect as antioxidants. The theoretical result is the same as the experimental result of antioxidants through the use of the quantum chemical calculations by calculating the energy gap (EHOMO-ELUMO). The best dispersant lube oil additive is (C).

Synthesis, anti-proliferative activity, gene expression, docking and DFT investigation of novel pyrazol-1-yl-thiazol-4(5H)-one derivatives

In this elucidation, the novel thaizolone derivatives 8a-n were synthesised via the reaction between thioamide derivatives 4a, b with chloroacetic acid and the appropriate aldehyde derivatives 7a-g in acetic acid which were confirmed through spectral analysis such as FT-IR, 1HNMR,13CNMR and mass spectrum. Furthermore, the optimization of these thiazolone were investigated utilized DFT/B3LYP/6-31(G) basis set and compared their energies and physical characterizations, which showed the most stable compounds from biphenyl and phenyl-piperidine fused thiazolone rings were 8f and 8m. The compounds 8f and 8m were exhibited as anti-proliferative compounds against MCF-7 breast cancer and PC-3 prostate cancer cells using neutral red uptake assay. Compound 8f showed more inhibitory influence on MCF-7 growth, while compound 8m revealed more cytotoxicity in PC-3 cells. The results were confirmed through a morphology study, where the expression levels of BCL2, Cyclin D1, FGF1 and HIF1α genes were examined by QRT-PCR. This study showed that compounds 8f and 8m exhibited significant pro-apoptotic effects, through the down regulation of BCl-2 and CCND1 genes. Also, the anti-angiogenic effect of compound 8f emerged due to the downregulation of FGF1 expression levels and the upregulation of HIF-1α. The stability and structural properties of the predicted conformers were studied using DFT theoretical calculations, which demonstrated that the stability of the anticipated conformers is affected by the configuration of the biphenyl and phenyl pipridine moieties in the synthesised thiazolone. Furthermore, the docking structures of these compounds 8f and 8m were investigated by (PDBID:4hdq), (PDBID:3ruk), (PDBID:5jsn) and (PDBID:5VZU) which confirmed the experimental results and showed the stability of 8f rather than 8m due to the presence of biphenyl and made more conjugation.

Cobalt(III)-catalyzed C-H amidation of N,N-dialkyl thiobenzamides by sulfur coordination.

An efficient inexpensive cobalt(III)-catalyzed intermolecular amidation of N,N-dialkyl thiobenzamides with 1,4,2-dioxazol-5-ones via C-H bond activation is described. The reaction proceeds with high functional group tolerance under external oxidant free conditions, providing a straightforward approach for the direct modification of thioamide derivatives, which are prevalent organic motifs found in vital biological and pharmaceutical molecules.

Synthesis of Fluorinated Amide Derivatives via a Radical N-Perfluoroalkylation-Defluorination Pathway.

A one-pot approach to fluorinated hydroxamic acid, amide, and thioamide derivatives is reported. The reaction proceeds via an N-perfluoroalkylation of nitrosoarenes with perfluoroalkanesulfinates, resulting in labile N-perfluoroalkylated hydroxylamines. By the addition of suitable additives, a controllable oxy/thiodefluorination of the fluorinated hydroxylamine intermediates was achieved. The method highlights N-perfluoroalkylated amines as versatile intermediates for further synthesis.

A copper-catalyzed multicomponent reaction for the synthesis of thioamide skeletons

In this report, in situ generated sulfide has been reacted with sulfonylketimine derived from the reaction of alkynes and sulfonyl azides by the action of copper salts to form a wide range of thioamide derivatives. Various terminal alkynes including aromatic, heteroaromatic, and aliphatic alkynes have been well tolerated and the reaction also shows good generality along with azides.

Synthesis of novel scaffolds based on thiazole or triazolothiadiazine linked to benzofuran or benzo[d]thiazole moieties as new hybrid molecules

A synthesis of novel hybrid molecules containing thiazole or bis(thiazoles) each bearing benzofuran and/or benzo[d]thiazole moieties by the reaction of the appropriate thioamide derivatives with the corresponding bis-bromoacetyl derivatives is reported. Mono- and bis(triazolothiadiazine) derivatives based on benzofuran or benzo[d]thiazole moieties were also synthesized in good yields by the reaction of the appropriate bis(bromoacetyl) derivatives with each of 4-amino-5-mercapto-1,2,4-triazoles and their corresponding bis-derivatives.

Synthesis of some novel pyrazoline‐thiazole hybrids and their antimicrobial activities

AbstractA series of novel thiazolyl pyrazolines 7a‐h, 9a‐f, and 11a‐f have been synthesized by the reaction of thioamide derivatives 5a,b with 1‐aryl‐2‐bromoethanones 6a‐d, chloroacetones 8a‐c, and hydrazonoyl chlorides 10a‐c. Additionally, pyrazoles 15a‐c and 20 were prepared starting from enaminone 13. These newly synthesized compounds were screened for their in vitro antibacterial activity against four bacterial species. Compound 11b showed a moderate activity against Klebsiella pneumoniae. Compounds 7c and 11c revealed a moderate activity against Pseudomonas aeruginosa. In addition, the antifungal activity of the newly synthesized compounds was determined against five fungal strains. Compounds 7e, 7g, and 11e showed a good activity against Aspergillus flavus and Penicillium expansum.