A New and Convenient Synthesis of Substituted Acylthioacylureas. Reaction of aryl and alkyl thioamides with acyl isocyanates

The addition of acyl isocyanates to a solution of aryl and alkyl thioamides affords substituted acylthioacylureas. The IR. spectra of substituted acylthioacylureas is described.     

Axially chiral thioamides of acrylic acid: correlated and uncorrelated internal rotations

In acrylic thioamides (Scheme. 1), two intramolecular motions are possible: thiocarbonyl–nitrogen (C–N) and alkenyl–carbonyl (C–C) rotations. Since the two mobile molecular fragments can interact by steric and by resonance effects, we intended to demonstrate the existence of correlated in addition to the above uncorrelated motions. For each of the three thioamides chosen, at least two of the four stereoisomers were enriched by crystallization and by liquid chromatography on nonracemic sorbents. Thereby axial chirality of acrylic thioamides was proven for the first time. Thermal equilibrations were monitored quantitatively by time-dependent ¹H NMR spectroscopy in the presence of a nonracemic additive, a method which, to our knowledge, has not previously been described. These kinetic results were evaluated by a simulation program with reference to uncorrelated and correlated rotations (Fig. 4, Fig. 5, Fig. 6). We have shown that all of these motions occur in thioamide 14. The enantiomers of thioamide 13 do not interconvert directly. However, indirect, two-step enantiomerizations in 13 have been proven one of the two steps consisting of correlated rotations. The latter are, therefore, possible in acrylic thioamides, a class of compounds which differ considerably from the molecules for which correlated motions were hitherto known.     

Copper-catalyzed chemoselective cross-coupling reaction of thioamides and α-diazocarbonyl compounds: Synthesis of enaminones

The development of operationally simple and cost-effective methods for CC bond formation reactions are highly important in pharmaceutical, agrochemical and material research. In this article we describe the first copper-catalyzed cross-coupling reaction of thioamides with acceptor/acceptor-substituted and acceptor-only substituted α-diazocarbonyl compounds to yield enaminones. The reaction shows broad substrate scope in terms of thioamides and diazocarbonyl compounds. Primary, secondary and tertiary thioamides all give enanminones when reacted with α-diazodiesters, α-diazoketoesters, α-diazodiketones, α-diazoketoamides, α-diazoesteramides, α-diazoketosulfones and α-diazomonoketones.     

Organocatalytic Domino Michael/cyclization for the synthesis of highly substituted 4, 5-dihydrothiophenes

Based on an umpolung strategy, a series of novel, full substituted, optically active dihydrothiophenes, which contain several functional groups, such as amine, ester and oxime groups, were obtained via an efficient organocatalytic asymmetric a formal thio[3 + 2]-cyclization of acyclic thioamides with (E)-α-nitrostyrenes.     

A facile and eco-friendly synthesis of diarylthiazoles and diarylimidazoles in water

A simple, efficient and high yielding greener protocol for the synthesis of substituted thiazoles and imidazoles is described that utilizes the reaction of readily available α-tosyloxy ketones with variety of thioamides/amidines in water.     

Green synthesis of 1,2,4-thiadizoles from thioamides in water using molecular oxygen as an oxidant

We present here an efficient green process for the synthesis of 1,2,4-thiadiazoles via iodine-catalyzed,oxidative dimerization of thioamides in water using molecular oxygen as a terminal oxidant. Under the optimized reaction conditions, aryl thioamides produced 3,5-diaryl-1,2,4-thiadiazoles in good to excellent yields. Alkyl thioamides and substituted thioureas could also provide corresponding 1,2,4-thiadiazole products.     

Harnessing sulfur and nitrogen in the cobalt(iii)-catalyzed unsymmetrical double annulation of thioamides: probing the origin of chemo- and regio-selectivity

An unconventional cobalt(iii)-catalyzed one-pot domino double annulation of aryl thioamides with unactivated alkynes is presented. Sulfur (S), nitrogen (N), and o,o′-C–H bonds of aryl thioamides are involved in this reaction, enabling access to rare 6,6-fused thiopyrano-isoquinoline derivatives. A reverse ‘S’ coordination over a more conventional ‘N’ coordination of thioamides to the Co-catalyst specifically regulates the formation of four [C–C and C–S at first and then C–N and C–C] bonds in a single operation, a concept which is uncovered for the first time. The power of the N-masked methyl phenyl sulfoximine (MPS) directing group in this annulation sequence is established. The transformation is successfully developed, building a novel chemical space of structural diversity (56 examples). In addition, the late-stage annulation of biologically relevant motifs and drug candidates is disclosed (17 examples). The preliminary photophysical properties of thiopyrano-isoquinoline derivatives are discussed. Density functional theory (DFT) studies authenticate the participation of a unique 6π-electrocyclization of a 7-membered S-chelated cobaltacycle in the annulation process.

A Co-catalyzed one-pot double annulation of sulfoximine bearing thioamides with alkynes for the synthesis of [6,6]-fused thiopyrano-isoquinolines is disclosed. The annulation involves a 6π-electrocyclization of 7-membered S-chelated cobaltacycle.     

Thioamide‐Directed Cobalt(III)‐Catalyzed Selective Amidation of C(sp3)−H Bonds

A mild, oxidant‐free, and selective Cp*Co^III‐catalyzed amidation of thioamides with robust dioxazolone amidating agents via C(sp³)−H bond activation to generate the desired amidated products is reported. The method is efficient and allows for the C−H amidation of a wide range of functionalized thioamides with aryl‐, heteroaryl‐, and alkyl‐substituted dioxazolones under the Cp*Co^III‐catalyzed conditions. The observed regioselectivity towards primary C(sp³)−H activation is supported by computational studies and the cyclometalation is proposed to proceed by means of an external carboxylate‐assisted concerted metalation/deprotonation mechanism. The reported method is a rare example of the use of a directing group other than the commonly used pyridine and quinolone classes for Cp*Co^III‐catalyzed C(sp³)−H functionalization and the first to exploit thioamides.     

O,O-Diethyl dithiophosphoric acid mediated direct synthesis of thioamides from aldehydes and ketones

A general and convenient method for a one-pot conversion of aldehydes and ketones into thioamides has been developed. The protocol involves oximation of aldehydes and ketones followed by deoxygenative thioamidation of oximes with O,O-diethyl dithiophosphoric acid which acts as an acid as well a source of sulfur. The method is operationally simple, high yielding, and also applicable to the conversion of amides and nitriles into the corresponding thioamides.     

The first example of a diastereoselective thio-Ugi reaction: a new synthetic approach to chiral imidazole derivatives

The first example of a diastereoselective thio-Ugi reaction with chiral alpha-methylbenzylamine is described. The reaction results in formation of two diastereomers of thioamides, the major of which was isolated. We have found that under similar conditions stereochemical results of the thio-Ugi reaction are opposite to stereochemical results of the Ugi reaction. Several chiral thioamides were synthesized. The reaction of thioamides with ammonia results in substituted amidines, which can be cyclized to imidazole derivatives in aqueous HCl. The synthesis of chiral imidazole derivatives was elaborated. Using certain approaches, both isomers of a key synthon in the synthesis of SB203386 (an orally bioactive HIV-1 protease inhibitor) were prepared. The scope, limitations, and stereochemistry of the approach are discussed.     

An efficient route for the synthesis of 2-arylthiazino[5,6-b]indole derivatives

Substituted 2-thiobenzamidomethylindole derivatives (14a-e) were prepared by the reaction of 2-aminomethylindole (9) with substituted benzoyl chlorides, followed by sulfurization using Lawesson's reagent. Alternatively, these thioamides were obtained from the amine in one step in an efficient manner by using substituted benzaldehydes in the presence of sulfur, or at room temperature with the aid of substituted methyl dithiobenzoates. The Hugerschoff reactions of thiobenzamides (14a-e) with phenyltrimethylammonium tribromide provided the rare title 2-arylthiazino[5,6-b]indoles (15a-e) in good yields. A convenient one-pot approach for the synthesis of 2-phenyl-1,3-thiazino[5,6-b]indole (15a) from 2-aminomethylindole (9) is also described.     

Heterocyclic compounds. VI. Synthesis of poly nuclear thienopyrimidine derivatives

Quinazoline derivatives have received great interest because of their potential biological activity. This communication describes a facile method for the synthesis of substituted thiophenopyrimidones. 2-Amino-3-earbethoxy-4,5-tetramethylenethiophene on heating with substituted imidoyl-chlorides, iminoethers, iminothioethers or thioamides affords thiophenopyrimidones. By using this method a number of such compounds of varying complexity were synthesized which are otherwise not so easily accessible.     

A novel one-pot synthesis of substituted 4-t-butyldimethylsilyloxy-thiazoles

The reaction of 2-halo-acylimidazolides or halides with primary thioamides in base give 2-halo-N-acylthioamides, which cyclize to the substituted 4-thiazolones and are trapped as the novel 4-t-butyldimethylsilyloxythiazoles in fair to good yield. The 2-aryl-4-t-butyldimethylsilyloxythiazoles undergo a [4+2] cycloaddition reaction with dimethoxyacetylene dicarboxylate [DMAD] to give substituted 2-pyridones in fair yield.     

Divergent regioselectivity in photoredox-catalyzed hydrofunctionalization reactions of unsaturated amides and thioamides

A direct method to construct 2-oxazolines and 2-thiazolines from corresponding allylic amides and thioamides is reported. The redox-neutral intramolecular hydrofunctionalization is enabled by a dual catalyst system comprised of 9-mesityl-N-methyl acridinium tetrafluoroborate and phenyl disulphide and exhibits complete selectivity for the anti-Markovnikov regioisomeric products. The cyclization of allylic thioamides is postulated to operate via a modified mechanism in which oxidation of the thioamide, rather than the alkene, is responsible for the observed reactivity.     

Remote ether groups-directed regioselective and chemoselective cycloaddition of azides and alkynes

Remote ether groups could be used as directing groups to prepare fully substituted 5-ether-1,2,3-triazoles with exclusive 1,5-regioselectivities and excellent chemoselectivities. Ether group could coordinate with iridium catalyst by lone-pair electron at a distance (up to four σ bonds) away from alkyne to control the regioselectivity by weak coordination effect. The cycloaddition reaction chemoselectively occurred at the propargyl ether moiety of diyne to give unique fully substituted 4-alkynyl-triazole.     

Thiocarbamoylation of 1,2,3,4-tetrahydroisoquinoline enamines with phenyl isothiocyanate

Reactions of 1,3,3-trimethyl-3,4-dihydroisoquinoline and its benzo[f] derivative with phenyl isothiocyanate gave the corresponding enamino thioamides. Enamino ester, enamino amides, and enamino nitriles of the 1,2,3,4-tetrahydroisoquinoline series reacted with phenyl isothiocyanate in a similar way. The resulting enamino thioamides underwent acylation with acid chlorides at the β-carbon atom of the enamino fragment. The structure of the obtained enamino thioamides is stabilized by intramolecular H-bonding.     

Synthesis of novel c-hetero-fused thiophene derivatives

An efficient synthesis of novel 5-(4-nitrophenyl)-2-benzoxazol-2-yl-c-hetero-fused thiophenes was achieved by the condensation of 5-(4-nitrophenyl)-2-benzoxazol-2-yl-3,4-dichlorothiophene with ethylene glycol, ethylenediamine, substituted thioamides and 2-mercaptobenzimidazole using sodium carbonate in refluxing dimethyl formamide.     

Progress in intermolecular and intramolecular reactions of thioamides with diazo compounds and azides

Reactions of thioamides with nitrogen-rich 1,3-dipoles, diazo compounds and azides, have been known for long time already. However in recent years introduction of catalysts of different types (rhodium-, ruthenium- and copper-containing and Lewis acids) as well as highly electrophilic sulfonyl azides, allowed the development of new methods for the synthesis of heterocycles, enamines and N-sulfonyl amidines. Moreover, a new methodology in organic synthesis, based on generation and subsequent transformations of α-diazocarbonyl compounds was created. Reactions of sulfonyl azides with thioamides undergo readily in mild conditions to produce different sorts of N-sulfonyl amidines and represent a new type of click-type processes. Most of the cited works were published in the current decade. Earlier seminal papers are also reviewed when they constitute the background for new synthetic methods which were developed further.     

Hyperconjugation effect on diene reactivity in 1-methyltetrazolo[5,1-a]isoindole-derived amides and thioamides

Optimized synthesis of 1-methyltetrazolo[5,1-a]isoindole-derived amides and thioamides was elaborated. Based on ¹³C NMR spectroscopy and X-Ray diffraction studies data, it was proposed that zwitterionic resonance structures contributed significantly to the structure of these compounds. Geometry optimization was performed in vacuo using m06-2x/cc-pvtz method taking into account polarizing effect of environment (PCM model) and specific intermolecular interactions. Electronic density distribution in these molecules was analyzed using NBO method. Using Δ(HOMO_diene–LUMO_dienophile) for amides and thioamides in vacuo and in a protic solvent, possibility of Diels–Alder reaction was evaluated. Energies of π-π conjugation and n→σ* hyperconjugation for the amide derivative were estimated in vacuo, aprotic and protic solvents.     

Amine nucleophilic addition to nitroalkene as a new practical approach for the synthesis of fully substituted isoxazoline-N-oxide

The secondary amine nucleophilic addition to the nitroalkene was used to generate the active nitronate intermediate, followed by the sequential addition to aldehyde and ylide, giving the fully substituted isoxazoline-N-oxide in one-pot fashion. Mechanistic studies revealed the equilibrium nature of the diene intermediates, which provide the foundation for the asymmetric synthesis of this interesting heterocycles.