Synthesis Of Thioamides Research Articles

One‐Pot Synthesis of Thioamides via Nickel‐Catalyzed Coupling of Thiocarbamoyl Fluorides and Boronic Acids

AbstractA novel and efficient one‐pot method has been developed for the synthesis of thioamides through coupling reactions between thiocarbamoyl fluorides, which are generated in situ from amines, and boronic acids. The key to the success of this transformation lies in the use of nickel a catalyst combined with PCy3 as a ligand. This innovative reaction protocol provides mild reaction conditions suitable for producing a diverse array of thioamides, and the late‐stage modification of amoxapine was successfully achieved.

Visible-Light-Driven Multicomponent Reactions for the Versatile Synthesis of Thioamides by Radical Thiocarbamoylation.

Thioamides are widely used structures in pharmaceuticals and agrochemicals, as well as important synthons for the construction of sulfur-containing heterocycles. This report presents a series of visible-light-driven multicomponent reactions of amines, carbon disulfide, and olefins for the mild and versatile synthesis of linear thioamides and cyclic thiolactams. The use of inexpensive and readily available carbon disulfide as the thiocarbonyl source in a radical pathway enables the facile assembly of structurally diverse amine moieties with non-nucleophilic carbon-based reaction partners. Radical thiocarbamoylative cyclization provides a practical protocol that complements traditional approaches to thiolactams relying on deoxythionation. Mechanistic studies reveal that direct photoexcitation of in situ formed dithiocarbamate anions as well as versatile photoinduced electron transfer with diverse electron acceptors are key to the reactions.

Visible‐Light‐Driven Multicomponent Reactions for the Versatile Synthesis of Thioamides by Radical Thiocarbamoylation

Thioamides are widely used structures in pharmaceuticals and agrochemicals, as well as important synthons for the construction of sulfur‐containing heterocycles. This report presents a series of visible‐light‐driven multicomponent reactions of amines, carbon disulfide, and olefins for the mild and versatile synthesis of linear thioamides and cyclic thiolactams. The use of inexpensive and readily available carbon disulfide as the thiocarbonyl source in a radical pathway enables the facile assembly of structurally diverse amine moieties with non‐nucleophilic carbon‐based reaction partners. Radical thiocarbamoylative cyclization provides a practical protocol that complements traditional approaches to thiolactams relying on deoxythionation. Mechanistic studies reveal that direct photoexcitation of in situ formed dithiocarbamate anions as well as versatile photoinduced electron transfer with diverse electron acceptors are key to the reactions.

A comprehensive investigation into the synthesis, characterization, and photocatalytic performance of modified graphene oxide via imino bond with ferrocene as a novel photocatalyst for thioamide synthesis

The study introduces a novel approach involving the amination of graphene oxide (GO) followed by the reaction with ferrocene–aldehyde, resulting in the formation of GO–NFc.

Contemporary Applications of Thioamides and Methods for Their Synthesis.

Thioamides are naturally occurring isosteres of amide bonds in which the chalcogen atom of the carbonyl is changed from oxygen to sulfur. This substitution gives rise to altered nucleophilicity and hydrogen bonding properties with importance for both chemical reactivity and non-covalent interactions. As such, thioamides have been introduced into biologically active compounds to achieve improved target affinity and/or stability towards hydrolytic enzymes but have also been applied as probes of protein and peptide folding and dynamics. Recently, a series of new methods have been developed for the synthesis of thioamides as well as their utilization in peptide chemistry. Further, novel strategies for the incorporation of thioamides into proteins have been developed, enabling both structural and functional studies to be performed. In this Review, we highlight the recent developments in the preparation of thioamides and their applications for peptide modification and study of protein function.

Construction of hybrid ionic liquid‐catalysts for the highly effective conversion of H2S by nitriles into thioamides

AbstractDescribed herein presents a kind of multisite hybrid ionic liquid‐catalysts and establishes a novel strategy for H2S utilization, which has been characterized by multiaspects to reveal internal structural characterization. Through chemical modification, the D101‐based hybrid ILs were used for the direct synthesis of thioamides from the addition of H2S and nitriles. D101‐[PMDETA][DMG] can achieve an impressive activity of quantitative conversion for benzonitrile. Reaction kinetics, adsorption thermodynamics, substrate universality, and catalyst cycling experiments have been systematically studied. A first‐order kinetic model was constructed and studied experimentally for the reaction of nitriles with H2S to produce thioamides. The internal mechanism was proposed through experiments and confirmed by DFT‐based theoretical calculations. Moreover, D101‐based hybrid ILs can be easily recovered, thus completing the cyclic process of thioamide multiplication. This work not only offers an effective method for the construction of organic‐inorganic hybrid materials but also provides a novel insight into efficient H2S conversion.

Copper‐Catalyzed Synthesis of Alkynyl Thioamides: An Efficient Thioacylation of Alkynes

AbstractA copper‐catalyzed efficient synthesis of alkynyl thioamides starting from tetraalkyl thiuram compounds (TMTM: tetramethyl thiuram monosulfide, TIBTM: tetraisobutyl thiuram monosulfide) and alkynes was reported. Thus, tetraalkyl thiurams reacted with alkynes smoothly, giving a variety of alkynyl thioamides promoted by CuI/Cs2CO3 system. This protocol features easy operation, inexpensive starting materials and good yields, illustrating its potential synthetic value for the synthesis of thioamides and their derivatives.

Towards More Practical Methods for the Chemical Synthesis of Thioamides Using Sulfuration Agents: A Decade Update.

Compounds possessing a thioamide function play a crucial role in organic synthesis, serving as key building blocks. They are also important in the pharmaceutical chemistry and drug design, owing to their ability to mimic the amide function in biomolecules while retaining or developing biological activity. From the synthetic viewpoint, several methods have been developed for preparing thioamides using sulfuration agents. The purpose of this review is to give an update of the last decade of contributions focusing on the formation of thioamides employing different sulfur sources. When appropriate, the cleanness and practicality of the new methods are highlighted.

Catalyst Free Synthesis of Thioamides from Pyrazole Aldehydes using DMSO as Solvent

A straightforward synthetic procedure for thioamides has been developed at 100 ºC using pyrazole aldehyde, a secondary amine, precipitated elemental sulphur and DMSO as solvent. The Willgerodt-Kindler reaction was successfully carried out by increasing the mole ratio of the precipitated sulphur and amine derivatives. The synthesized thioamides derivatives were characterized by 1H and 13C NMR, FT IR, HRMS spectrometric techniques. This method has various advantages, including high yields, a relatively rapid reaction time and the ability to operate in catalyst-free conditions.

Palladium-Mediated CO2 Extrusion Followed by Insertion of Allenes: Translating Mechanistic Studies to Develop a One-Pot Method for the Synthesis of Alkenes

A palladium-mediated one-pot synthesis of alkenes from aromatic carboxylic acids and allene substrates (R1R2C═C═CH2, where either: R1 = Ph, R2 = H; R1 = Ph, R2 = Me or R1 = nPe, R2 = H) is reported. This is an isoelectronic variant of CO2 extrusion–insertion (ExIn) reactions previously developed using heterocumulenes for the synthesis of thioamides (from isothiocyanates, RNCS), amidines (from carbodiimides, RNCNR), and amides (from isocyanates, RNCO). Evidence that the key aryl-palladium intermediate reacts to form a stable allyl-palladium product via insertion of the allene at the C2 position that enables the synthesis of alkenes was provided by a combination of gas-phase multistage mass spectrometry (MSn) experiments and condensed-phase monitoring using 1H NMR spectroscopy as well as theoretical computational data. Isolation and X-ray crystallographic analysis of the salt [(phen)Pd(CH2CH(Ar)CHPh)]+(CF3CO2–) (where Ar = 2,6-dimethoxyphenyl) confirmed insertion of the allene at the C2 position and revealed a syn relationship between the two aryl groups. A survey of different hydrogen sources to promote the removal of palladium from the alkene product revealed that NaBH4 provides the highest yield and with the Z-alkene as the major isomer.

Europhtal: An industrial cobalt phthalocyanine complex as the efficient catalyst for synthesis of thioamides by one‐pot reaction of mercaptans and amines

AbstractThe potential of industrial cobalt phthalocyanines in the synthesis of thioamides is reported. A mixture of an industrial sulfonated cobalt phthalocyanines known as Co[(SO3Na)2,3Pc] (Europhtal catalyst additive 8020) is introduced as an efficient catalyst capable of converting benzyl thiols to synthetically valuable thioamides by reaction with amines and DMSO. In this procedure, different primary and secondary amines also heterocyclic amines were successfully converted into benzothioamides in high yields. This simple, one‐pot three‐component conversion method is scalable and provides efficient and practical route to the synthesis of diverse benzothioamides.

Ynamide-Mediated Thioamide and Primary Thioamide Syntheses.

Environmentally friendly ynamide-mediated thioamidation of monothiocarboxylic acids with amines or ammonium hydroxide for the syntheses of thioamides and primary thioamides is described. Simple and mild reaction conditions enable the reaction to tolerate a wide variety of functional groups such as hydroxyl group, ester, tertiary amine, ketone, and amide moieties. Readily available NaSH served as the sulfur source, avoiding the use of toxic, expensive, and malodorous organic sulfur reagents and making this strategy environmentally friendly and practical. Importantly, the stereochemical integrity of α-chiral monothiocarboxylic acids was maintained during the activation step and subsequent aminolysis process, thus offering a racemization-free strategy for peptide C-terminal modification. Furthermore, a number of thioamide-modified drugs were prepared in good yields by using this protocol and the synthesized primary thioamides were transformed into backbone thiazolyl modified peptides.

Water Mediated Direct Thioamidation of Aldehydes at Room Temperature.

A mild, greener approach toward thioamide synthesis has been developed. Its unique features include water-mediated reaction with no input energy, additives, or catalysts as well. The presented protocol is attractive with readily available starting materials and the use of different array amines, along with a scaled-up method. Biologically active molecules such as thionicotinamide and thioisonicotinamide can be synthesized from this procedure.

Cellulose-reinforced poly(ethylene-co-vinyl acetate)-supported Ag nanoparticles with excellent catalytic properties: synthesis of thioamides using the Willgerodt-Kindler reaction.

Cellulose, a bio-derived polymer, is widely used in food packaging, dye removal, coatings, and solid-supported catalysis. Heterogeneous catalysts play a critical role in environmental remediation. In this context, the demand for green and cost-effective catalysts has rapidly increased. In this study, cellulose was extracted from rice straw, and a highly active solid-supported catalytic model was developed. First, cellulose was conjugated with poly(ethylene-co-vinyl acetate) (PEVA), and then Ag nanoparticles (AgNPs) were inserted into the cellulose–PEVA composite. The process involved the reduction of AgNPs in the presence of sodium borohydride. The fabricated hybrid catalyst was characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray, and powder X-ray diffraction. Thereafter, the obtained hybrid was used as a catalyst for the Willgerodt–Kindler reaction of aromatic aldehydes, amines, and S8 to synthesize thioamides with excellent yields. The developed catalytic system exhibited high stability and recyclability. Moreover, the mechanical properties of the hybrid catalyst were evaluated using tensile strength and impact tests. RGB analysis of digital images was also performed to investigate the primary components of the catalyst.

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.

Study on the synthesis of thioamides from aldehyde N-tert-butylsulfinyl amide and sulfur in aqueous media

Thioamides have been widely used in the fields of medicine and organic chemistry, some of which are essential bioactive compounds, plant protection agents, and drugs. It could also be used as a vulcanizing agent, an additive to lubricants and greases, and a ligand in organic synthesis. Usually, thioamide is synthesized at high temperatures or in the microwave using an expensive noble metal complex as catalysts. This paper presented a straightforward method for synthesizing thioamides by using N-tert-butylsulfinyl amide, aldehyde, and sulfur. The reaction was carried out in water, which is an environmentally friendly solvent. The reaction selectivity and yield were up to 89%.

General Construction of Thioamides under Mild Conditions: A Stepwise Proton Transfer Process Mediated by EDTA

AbstractA general and clean method for the one‐pot synthesis of thioamides was investigated using a combination of experiments and quantum chemical calculations. Ester, amide, and elemental sulfur were employed as starting materials and ethylene diamine tetraacetic acid (EDTA) as catalyst. Both alkyl and aryl thioamides with various functional groups were obtained in moderate to good yields. Neither transition metals nor external oxidants were required in this reaction. The catalytic performance of EDTA originates from a stepwise, proton transfer process in which EDTA transports a proton from the benzyl carbon to a sulfur atom. Such a process is concerted by discrete charge transfer such that the associated barrier gets lowered.

Transition‐Metal‐Free, General Construction of Thioamides from Chlorohydrocarbon, Amide and Elemental Sulfur

AbstractA general method for one‐pot synthesis of thioamides is developed through a three‐component reaction involving chlorohydrocarbon, amide and elemental sulfur. Such a strategy does not only avoid residual transition metal in the product but also prevent the generation of C−N coupling by‐product. The latter is prone to be generated when alkane halide and amine are present. With the protocol proposed in this work, both alkyl and aryl thioamides can be obtained in moderate to excellent yields with a high tolerance of various functional groups. External oxidants are not required in the reaction. In addition, the reaction mechanisms are addressed using a combination of controlling experiments and quantum chemical calculations.

Synthesis of thioamides from thiocarboxylic acids using phosphonium-type condensing reagents

The synthesis of thioamides via the condensation reaction of thiocarboxylic acids with amines is described. Using 3-cyano-1,2,4-triazole as a favorable nucleophilic catalyst and 3-cyano-1,2,4-triazol-1-yl-tris(pyrrolidine-1-yl)phosphonium hexafluorophosphate (PyCTP) as a new phosphonium-type condensing reagent, thioamides are obtained selectively over amides, which can be attributed to the hardness of the phosphorus center of the condensing reagent.

Metal-free three-component synthesis of thioamides from β-nitrostyrenes, amines and elemental sulfur

A metal-free CC bond cleavage reaction of β-nitrostyrenes in the presence of elemental sulfur and secondary amines/amides is described. Elemental sulfur serves as both a raw material and an oxidant for CC bond cleavage, and secondary amines or amides are both feasible nitrogen sources. Besides mild reaction condition and simple work-up procedure, the method provided thioamides with good to excellent yields.