Primary Thioamides Research Articles

Application of thioamides as sulfur sources to the synthesis of thieno[2,3-b]quinoxalines

An efficient synthesis of thieno[2,3-b]quinoxalines by thiolative cyclization of 2-chloro-3-(phenylethynyl)quinoxalines using primary thioamides as sulfur sources has been proposed. The reactions provided moderate to good yields under mild conditions.

Transamidation of Primary Thioamides with Primary and Secondary Amines via C(S)–N Bond Cleavage and Formation by Hydroxylamine Hydrochloride Catalysis

Transamidation of Primary Thioamides with Primary and Secondary Amines via C(S)–N Bond Cleavage and Formation by Hydroxylamine Hydrochloride Catalysis

Palladium and platinum complexes of primary 2-pyridinethioamide

Primary thioamide, 2-pyridinethioamide reacts with palladium and platinum compounds K2PdCl4, K2PtCl4 and Pd(CH3COO)2 to give the products [PdCl2(2-pyridinethioamide)].2DMF (1), [PtCl2(2-pyridinethioamide)] (2a), [Pd(2-pyridinethioamide)2]Cl2 (3), [Pt(2-pyridinethioamide)2]Cl2 (4) and [Pd(2-pyridinethioamidinate)2] (5), respectively. The structures 1, [PtCl(DMSO)(2-pyridinethioamidinate)] (2b), which was obtained from crystallization of 2a in DMSO, 4 and 5 were determined by X-ray crystallography. Compound 3 was spectroscopically analyzed and found to have a structure similar to that of 4. The ligand coordinates in a neutral form in complexes 1, 2a, 3 and 4, but in 2b and 5 it exists in a deprotonated form. Compounds 3 and 4 are cationic complexes with Cl− counterions in the structure. The ligand prefers coordination as the bidentate N(py),S-mode in all the crystallized compounds. In the bis-chelates, the sulfur and the nitrogen atoms are mutually trans-located. Computational DFT calculations and topological charge density analysis were utilized to clarify the coordination modes and to interpret the spectral information.

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

Reactions of thiobenzamide or thioacetamide with 4-bromo-1,1-dimethyl-1,4-dihydroisoquinoline-3(2H)-one, 4-bromoisoquinoline-1,3(2H,4H)-dione and two α-bromo(phenyl)acetamides were examined under various conditions (base, solvent, thiophile, temperature) and structure/medium features that influence product distribution (Eschenmoser coupling reaction, Hantzsch thiazole synthesis and elimination to nitriles) were identified. The key factor that enables the successful Eschenmoser coupling reaction involves the optimum balance in acidity of nitrogen and carbon atoms of the intermediary α-thioiminium salts.

The effect of halogens in the coordination of 2-pyridinethioamide to gold centers

Primary thioamide, 2-pyridinethioamide reacts with gold compounds Na[AuCl4], [AuCl(tetrahydrothiophene)], AuBr3 and AuI to [AuCl2(2-pyridinecarboxamide)] (1), [AuCl(2-pyridinethioamide)]3 (2), [AuBr(2-pyridinethioamide)]3 (3), and [AuI(2-pyridinethioamide)] (4), respectively. Formation of 1 involves interconversion of thioamide to amide and creation of a N,Ń-auracycle. Compounds 2 and 3 both consist of linear trimeric adducts with aurophilic interactions between the gold atoms. In these compounds, the sulfur donor ligands show monodentate coordination. Similar monomeric unit is present in 4, which in solid state produces dimers via SS chalcogen interactions. The structures were determined by X-ray crystallography. Computational DFT calculations and topological charge density analysis were utilized to clarify interactions, which determine the structures in solid state.

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.

Selectively Oxidative Thiolysis of Nitriles into Primary Thioamides and Insecticidal Application

AbstractPrimary thioamides are useful building blocks for drug and insecticide development, therefore an environmentally benign synthesis of primary thioamides is desired. This paper discloses an oxidative thiolysis for the selective transformation of nitriles into primary thioamides using elemental sulfur or thiuram in the presence of K2S2O8 in DMF/H2O. This practical method enables access to a wide range of synthetically and pharmaceutically useful primary thioamides. Advantages of this reaction include transition‐metal‐free and base‐free reaction conditions, use of an environmentally benign solvent (DMF/H2O) system, the use of non‐toxic elemental sulfur or thiuram as the sulfur sources, and good functional groups tolerances with excellent selectivity. Furthermore, the insecticide Fipronil can also be converted to the corresponding thioamide and maintains excellent bioactivity against P. xylostella. The LC50 value of Fipronil thioamide is 1.25 mg/L.

Highly efficient synthesis of 1,2,4-thiadiazoles from thioamides utilizing tetra(n-butyl)ammonium peroxydisulfate

A new synthetic approach to 1,2,4-thiadiazoles using tetra(n-butyl)ammonium peroxydisulfate via oxidative dimerization of thioamides is described. This new oxidative protocol is simple, highly efficient, and allows the practical synthesis of 1,2,4-thiadiazoles from various primary thioamides in good to excellent yields.

Expedient Synthesis of 1,2,4‐Thiadiazoles from Primary Thioamides Using Calcium Hypochlorite in Dichlomethane

Expedient synthesis of 1,2,4-thiadiazoles from primary thioamides using calcium hypochlorite in dichloromethane. Appendix S1. Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Triphenylbismuth Dichloride‐Mediated Conversion of Thioamides to Nitriles

Thioamides were efficiently converted to nitriles using the pentavalent triphenylbismuth dichloride in combination with triethylamine. The reaction involved the dehydrosulfurization of primary thioamides to afford substituted aromatic or aliphatic nitriles in good to excellent yields. The process was also successfully extended to the synthesis of cyanamides starting from the corresponding thioureas and of thiocyanates from dithiocarbamates.

Tert-Butyl nitrite induced radical dimerization of primary thioamides and selenoamides at room temperature

A simple and efficient method for the dimerization of primary thioamides into 1,2,4-thiadiazoles using tert-butyl nitrite is described. The optimized condition was also found to be suitable for the dimerization of benzoselenoamides into 1,2,4-selenadiazoles. All the reactions proceed smoothly at room temperature and gave the desired products in excellent yields in a short span of time.

ChemInform Abstract: High Yielding Protocol for Oxidative Dimerization of Primary Thioamides: A Strategy Toward 3,5‐Disubstituted 1,2,4‐Thiadiazoles.

AbstractCeric ammonium nitrate is used as an oxidant for the rapid oxidative dimerization of primary thioamides to afford thiadiazoles.

A Simple and Convenient Method for the Synthesis of 3,5‐disubstituted 1,2,4‐thiadiazoles via Oxidative Dimerization of Primary Thioamides

A simple and efficient protocol has been developed for the preparation of 3,5‐diaryl‐1,2,4‐thiadiazoles in high yields through the oxidative dimerization of primary thioamides in aqueous medium at room temperature.

High yielding protocol for oxidative dimerization of primary thioamides: a strategy toward 3,5-disubstituted 1,2,4-thiadiazoles

Ceric ammonium nitrate (CAN), a highly versatile reagent, was found to efficiently mediate the oxidative dimerization of primary thioamides in acetonitrile at room temperature leading to the rapid and expeditious synthesis of symmetrically 3,5-disubstituted 1,2,4-thiadiazoles in high yields.

L-Proline: An Efficient and Selective Catalyst for Transamidation of Thioamides with Amines

L-Proline catalysed transthioamidation of primary thioamides with amines under solvent-free conditions has been described. The transthioamidation is compatible with wide range of amines with yields up to 97%.

Investigating C═S···I Halogen Bonding for Cocrystallization with Primary Thioamides

Cocrystallization utilizing halogen bonding involving the thiocarbonyl functional group of a series of primary aromatic thioamides has been investigated. The well-known organoiodide 1,4-diiodotetrafluorobenzene was utilized as the halogen bond donor and the C═S···I halogen bond was established as a robust supramolecular synthon in these systems. Weak N–H···S hydrogen bonding involving the thioamides influences the overall supramolecular architectures, meaning that there is a diverse range of structural motifs and cocrystal stoichiometries observed. The majority (60%) of the cocrystals obtained have a 2:1 ratio of thioamide/organiodide with the latter present over an inversion center. The higher ratio of organoiodide seen in the other cocrystals is achieved by additional I···I and I···π halogen bonding. The C═S···I halogen bond is replaced by N···I halogen bonding in the one cocrystal containing a pyridyl-substituted thioamide. The ability of the thioamides to form cocrystals and the strength of the haloge...

Selective thioacylation of amines in water: a convenient preparation of secondary thioamides and thiazolines

Preparation of secondary thioamides and thiazolines via formation of β-hydroxythioamides from primary thioamides and aminoethanol in water.

ChemInform Abstract: Facile Access to 3,5‐Symmetrically Disubstituted 1,2,4‐Thiadiazoles Through Phosphovanadomolybdic Acid Catalyzed Aerobic Oxidative Dimerization of Primary Thioamides.

In the presence of Keggin-type phosphovanadomolybdic acids, e.g., H6PV3Mo9O40, oxidative dimerization of various kinds of primary thioamides including aromatic, heterocyclic, and aliphatic ones efficiently proceeded to give the corresponding 3,5-disubstituted 1,2,4-thiadiazoles in excellent yields.

Synthesis of Rhodium–Primary Thioamide Complexes and Their Desulfurization Leading to Rhodium Sulfido Cubane-Type Clusters and Nitriles

Although molecular thioamide complexes of late-transition metals have been prepared since 1979, the chemistry of primary thioamide complexes remains relatively unexplored. To shed light on this area, we have investigated synthesis, structures, and reactivities of simple rhodium organometallic complexes with a primary arenecarbothioamide ligand [Cp*RhCl2{S═C(Ar)NH2-κ1S}] (Cp* = η5-C5Me5). Intra- and intermolecular hydrogen bonding in the thioamide complexes is discussed on the basis of 1H NMR spectroscopy and X-ray analysis. When these rhodium complexes were treated with a large excess amount of Et3N, desulfurization of the thioamide ligand took place to give arenecarbonitriles (ArCN) in high GC yield and the cubane-type cluster [(Cp*Rh)4(μ3-S)4] (3) in good yield as the organometallic product. Use of a smaller amount (2.4 equiv) of Et3N followed by treatment with NaBArF4 (ArF = 3,5-(CF3)2C6H3) led to the isolation of the cationic clusters [(Cp*Rh)4(μ3-S)4](BArF4) or [(Cp*Rh)4(μ3-S)4](BArF4)2 in low yield. Reaction mechanisms of the desulfurization of the coordinated thioamides and the formation and one- or two-electron oxidation of 3 during the desulfurization are discussed.

Halogen Bonding with Sulfur Functional Groups

Crystal engineering has been defined as "the understanding of intermolecular interactions in the context of crystal packing and the utilisation of such understanding in the design of new solids with desired physical and chemical properties".[1] Halogen bonding is a significant type of intermolecular interaction involving a halogen atom with neutral or anionic components which has recently been exploited for the formation of multicomponent crystalline materials. Sulfur can exist in a variety of different oxidation states, giving rise to a wide variety of different functional groups that are potentially available for halogen bonding. We have recently reported our investigations with sulfoxide,[2] sulfone[2] and sulfinamide functional groups.[3] Herein we extend this work to include the thioamide functional group and compare it with its more extensively studied amide analogue. Investigation into the propensity for primary aromatic thioamides to form halogen interactions through the thiocarbonyl (C=S) functional group. A range of substituent aromatic primary thioamides containing different electronic substituents on the aromatic ring were synthesized and investigated for cocrystallisation. These cocrystals are held together by a combination of weak hydrogen bonding (N–H···S=C) and strong halogen interactions (C–X···S=C).