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An efficient reduction of sulfoxides to sulfides mediated by N-bromosuccinimide (NBS)/HCl system has been developed. This protocol shows good functional group compatibility as well as broad substrates scope with operational simplicity.

Ni-catalyzed C?S cross-coupling reactions have received less attention compared with other C-heteroatom couplings. Most reported examples comprise the thioetherification of most reactive aryl iodides with aromatic thiols. The use of C?O electrophiles in this context is almost uncharted. Here, we describe that preformed Ni(II) precatalysts of the type NiCl(allyl)(PMe2Ar’) (Ar’=terphenyl group) efficiently couple a wide range of (hetero)aryl halides, including challenging aryl chlorides, with a variety of aromatic and aliphatic thiols. Aryl and alkenyl tosylates are also well tolerated, demonstrating, for the first time, to be competent electrophilic partners in Ni-catalyzed C?S bond formation. The chemoselective functionalization of the C?I bond in the presence of a C?Cl bond allows for designing site-selective tandem C?S/C?N couplings. The formation of the two C-heteroatom bonds takes place in a single operation and represents a rare example of dual electrophile/nucleophile chemoselective process.

Abstract: Diaryl sulfides have been synthesized in moderate to excellent yield by S-arylation of arenethiols with arylboronic acids using copper slag as a catalyst. Copper slag is a by-product obtained from smelting and refining of copper. Conventional heating method has been compared with the microwave-assisted technique. The proposed microwave-assisted synthesis provides excellent yields of diaryl sulfides in a short time (10 min) and is ligand-free, green, and cost-effective.

A NiCl2/2,2′-bipyridine-catalyzed cross-coupling of thiophenols with arylboronic acids has been developed for the synthesis of symmetric and unsymmetric diarylsulfides at room temperature and in air. This methodology is reliable and offers a mild and easy to operate process for the synthesis of arylthioethers, which are essential compounds with applications in the pharmaceutical and agricultural industries. This method avoids the use of expensive transition metals, such as Pd, Ir or Rh, sophisticated ligands and elevated temperatures. It also has a wide substrate scope (55 examples) and provides products in good to excellent yields (72-93%).

A simple and efficient approach of C-S cross-coupling of a wide variety of (hetero)aryl thiols and (hetero)aryl halides under mild conditions, mostly at room temperature, catalyzed by well-defined singlet diradical Ni(II) catalysts bearing redox noninnocent ligands is reported. Taking advantage of ligand centered redox events, the high-energetic Ni(0)/Ni(II) or Ni(I)/Ni(III) redox steps were avoided in the catalytic cycle. The cooperative participation of both nickel and the coordinated ligands during oxidative addition/reductive elimination steps allowed us to perform the catalytic reactions under mild conditions.

In this work, we report a simple and versatile method for the modification of a metal-organic framework (NH2-MIL53(Al)) in a step-wise manner. To characterize the synthesized nanostructured catalyst, a variety of spectroscopic and microscopic techniques including FT-IR, XRD, BET, TEM, FE-SEM, EDX, EDX-mapping, TGA, XPS, VSM, ICP-OES and CHN have been employed. Fe3O4@AMCA-MIL53(Al)-NH2-CoII NPs, which benefit from small nanocrystalline size (10-30 nm, according to the XRD and TEM data) in combination with the coexistence of magnetic nanoparticles, a metal-organic framework, and cobalt species, were found to be an excellent environment catalyst to promote the C-N and C-S cross coupling reactions. A wide range of functional substrates including electron-withdrawing and electron-donating aryl halides underwent the coupling reaction with aromatic/heteroaromatic/benzylic and aliphatic amines and sulfides. The results demonstrated that the yields of the target products were good to excellent and the catalyst can be recycled for at least seven recycling runs without a discernible decrease in its catalytic activity. Furthermore, the heterogeneity studies (such as hot filtration and poisoning tests) efficiently confirmed that the as-synthesized nanostructured catalyst is heterogeneous and completely stable under the reaction conditions. We hope that our study inspires more interest in designing novel catalysts based on using low-cost metal ions (such as cobalt) in the field of cross coupling reactions.

The Chan–Lam coupling reaction starting from phenyldithiocarbamates and phenylboronic acids is reported. To avoid using the volatile, hazardous, and foul-smelling thiols, which are sometimes expensive and not sufficiently available, phenyldithiocarbamates can be employed. They are demonstrated to be good sulfuration reagents in the Chan–Lam coupling to prepare biaryl sulfides. By using this protocol, dithiocarbamate substrates with a wide range of functional groups including electron-rich and electron-deficient ones are explored to obtain the desired substituted biaryl sulfides smoothly. This method is ligand-free, has a broad substrate scope, enables good yields, and is easy to perform. It provides a facile and convenient preparation of biaryl sulfides.

In one aspect, the invention provides a method of promoting a carbon-sulfur bond forming reaction. In certain embodiments, the reaction comprises cross-coupling of a(n) (hetero)aryl halide with a thiol to form the carbon-sulfur bond, wherein the method is promoted by light irradiation in the absence of a photocatalyst. In other embodiments, the cross-coupling reaction can be promoted through visible light irradiation, including sunlight.

A nickel-catalyzed C–S bond-formation protocol for the synthesis of diaryl sulfides is described. In a reaction catalyzed by NiCl2, phenyldithiocarbamates react with iodobenzenes to give diaryl sulfides smoothly in good to excellent yields (66–93 %). The catalyst is cheap, the reaction is easy to carry out, the substrate scope is broad, and the yields are good. Thus, this gives an alternative way to prepare diaryl sulfides.

Disclosed is a mild, scalable, visible-lightpromoted cross-coupling reaction between thiols and aryl halides for the construction of C-S bonds in the absence of both transition metal and photoredox catalysts. The scope of aryl halides and thiol partners includes over 60 examples and therefore provides an entry point into various aryl thioether building blocks of pharmaceutical interest. Furthermore, to demonstrate its utility, this C-S coupling protocol was applied in drug synthesis and latestage modifications of active pharmaceutical ingredients. UV-vis spectroscopy and time-dependent density functional theory calculations suggest that visible-lightpromoted intermolecular charge transfer within the thiolate-aryl halide electron donor-acceptor complex permits the reactivity in the absence of catalyst.

Regioselective arylthiolations of aromatic amines, arenols and ketones via C–H bond functionalization have been achieved with I2and PPh3in an aqueous system, whereby arylsulfenyl radicals are in situ generated from odorless sodium arylsulfinates. The arylsulfenyl radicals can react with free anilines containing electron-withdrawing groups and complex substrates (estrone and progesterone). Further experiments and quantum chemical calculations were also performed to deduce a mechanism for the formation of arylsulfenyl radicals. (Figure presented.).

An efficient TBATB mediated debenzylative cross coupling of aryl benzyl sulfides with electron rich compounds provides diaryl sulfides in moderate to excellent yield. The salient features of the present protocol are simplicity, high efficiency and compati

Sub-nanometric Cu clusters formed by endogenous reduction of Cu salts and Cu nanoparticles are active and selective catalysts for C-N, C-C, C-O, C-S, and C-P bond-forming reactions. Sub-nanometric Cu clusters have also been generated within a polymeric film and stored with full stability for months. In this way, they are ready to be used on demand and maintain high activity (TONs up to 104) and selectivity for the above reactions. A potential mechanism for the formation of the sub-nanometric clusters and their electronic nature is presented.

A simple, efficient and environmentally friendly method for iron or boron-catalyzed C-H arylthiation of substituted phenols at room temperature has been developed, and the corresponding diaryl sulfides were prepared in good to excellent yields. The protocol uses readily available 1-(substituted phenylthio)pyrrolidine-2,5-diones as the arylthiation reagents and inexpensive and environmentally friendly FeCl3 or BF3·OEt 2 as the catalyst, moreover no ligands, additives or extrusion of air are required, and the reactions can be performed successfully at room temperature. This journal is the Partner Organisations 2014.

The preparation of diaryl and alkyl aryl sulfides via acid-mediated coupling of thiols and thioethers with diaryliodonium salts is reported. The scope, limitations, and mechanism of the transformation are discussed.

An efficient, CuI catalyzed, ligand free, synthetic protocol for thioethers has been developed by using nitroarenes. A variety of thiols and nitroarenes was scanned by using this method to produce aryl sulfides. Newly developed method demonstrates a new alternative to existing method which is cost effective approach to synthesize nonsymmetrical aryl thioethers.

The AgNO3-mediated in situ scission of aromatic disulfides in the presence of electron-rich aromatic compounds results in the efficient synthesis of diaryl sulfides. Key features of this new methodology are high yields of aromatic and heteroaromatic sulfides, mild reaction conditions, simplicity, simple workup, and avoiding foul-smelling reactants like thiols. Georg Thieme Verlag Stuttgart · New York.

A transition-metal-free synthetic method has been developed for the synthesis of unsymmetrical diaryl chalcogenides (S, Se, and Te) from diaryl dichalcogenides and arenes under oxidative conditions by using potassium persulfate at room temperature. Variously substituted arenes such as anisole, thioanisole, diphenyl ether, phenol, naphthol, di- and trimethoxy benzenes, xylene, mesitylene, N,N-dimethylaniline, bromine-substituted arenes, naphthalene, and diaryl dichalcogenides underwent carbon-chalcogen bond-forming reaction to give unsymmetrical diaryl chalcogenides in trifluoroacetic acid. To understand the mechanistic part of the reaction, a detailed in situ characterization of the intermediates has been carried out by 77Se NMR spectroscopy by using diphenyl diselenide as the substrate. 77Se NMR study suggests that electrophilic species ArE+ is generated by the reaction of diaryl dichalcogenide with persulfate in trifluoroacetic acid. The electrophilic attack of arylchalcogenium ion on the arene may be responsible for the formation of the aryl-chalcogen bond.

In this work, an efficient CuSO4-catalyzed S-arylation of thiols with aryl and heteroaryl boronic acids at room temperature is established. This catalytic system can tolerate a wide variety of thiols and arylboronic acids in the presence of only 5 mol % of CuSO4 as the catalyst and inexpensive 1,10-phen?H2O as the ligand. Moreover, this catalytic system used environment-friendly solvent (EtOH) and oxidant (oxygen).

A highly efficient and ligand-free copper(I) sulfide catalyzed cross-coupling reaction of aryl iodides with diaryl disulfides was developed. With only 1 mol-% of Cu2S as the catalyst, iron powder as the reductant, and K2CO3 as the base, aryl iodides reacted with disulfides in DMSO at 90-110 °C for 18-24 h under an atmosphere of argon to give the corresponding aryl sulfides in good to excellent yields. In addition, the catalyst is recyclable and reusable with some loss of activity.

(Chemical Equation Presented) A catalytic amount of zinc chloride in combination with a palladium catalyst ligated by a monodentate phosphine allows the coupling of aryl and alkyl thiols with aryl bromides in high yields. The addition of zinc chloride to a palladium catalyst system that reportedly failed to promote sulfide formation allows this once ineffective catalyst system to provide the sulfide product in good yield. This paper describes a high-yielding and general monodentate phosphine-ligated palladium catalyst for biaryl and alkyl aryl sulfide formation.

A mild, general, and efficient copper-catalyzed system for C-S bond formation with high chemoselectivity and wide functional group tolerance is developed. With CuBr as catalyst and 1,2,3,4-tetrahydro-8-hydroxy-quinoline as ligand, the S-arylation of thiols with aryl halides performed well, the activated aryl iodides could take place even at room temperature, and the activated aryl bromides and chlorides give the corresponding products with good to excellent yields as well.

A new protocol for the coupling of aryl iodides with thiophenols or alkanethiols is reported. The reaction is catalyzed by CuI-PEG or CuI-PEG-H2O system in the absence of ligands and volatile organic solvents. A variety of functionalized aryl sulfides are prepared in excellent yields. The isolation of the products is readily performed by the extraction with diethyl ether or petroleum ether, and the CuI-PEG catalyst can be reused without significant loss in activity. The simple catalytic system is economically competitive and environmentally friendly.

Indium-catalyzed C-S cross-coupling of aromatic and alkane thiols with aryl halides proceeds smoothly in the presence of In(OTf)3 (10 mol %), TMEDA (20 mol %), and KOH as a base in DMSO at 135 °C. When this protocol was utilized, a variety of thiols could be cross-coupled with aryl halides to afford the corresponding aryl sulfides in good to excellent yields.

(Chemical Equation Presented) This article describes the methodology for a copper-catalyzed preparation of numerous monochalcogenides from dichalcogenides with organoboronic acids. Unsymmetrical diorgano-monosulfides, selenides, and tellurides can be synthesized by the coupling of dichalcogenides with aryl- or alkylboronic acids using a copper catalyst in air. The present reaction can take advantage of both organochalcogenide groups on dichalcogenide.

Disclosed is an efficient and widely-applicable method for commercially producing a thioether compound or a thiol compound which is useful as a pharmaceutical compound or a production intermediate of it. Specifically disclosed is a method for producing a thioether compound represented by the general formula [I] below or a salt thereof. This method is characterized in that a compound represented by the following general formula [III]: [III] (wherein X represents a bromine atom, a chlorine atom or a trifluoromethylsulfonyloxy group, and ring A represents an aryl group or a heteroaryl ring group) or a salt thereof is reacted with a thiol compound represented by the following general formula [II]: [II] or a salt thereof in the presence of a palladium compound such as Pd2(dba)3, a base such as i-Pr2NEt and a phosphorus compound represented by the following formula [AA].

Diaryl chalcogenide synthesis employing diaryl dichalcogenides and aryl halides as starting materials in the presence of excess magnesium and a catalytic amount of CuI/bipyridyl is significantly improved by microwave heating. Reaction times can be reduced from 2 to 3 days to 6-8 h. Both aryl bromides and aryl chlorides can be used as substrates in the substitution reaction. The procedure is useful not only for diaryl sulfide and diaryl selenide synthesis but also for the preparation of unsymmetrical diaryl tellurides. Starting from suitable aryl halides, the novel microwave-assisted procedure was used for the facile preparation of novel chalcogen analogues (PhS-, PhSe-, and PhTe-) of various antioxidants (ethoxyquin and 3-pyridinol). Attempts to use dialkyl dichalcogenides for the coupling of alkylchalcogeno moieties to aryl halides were only successful in the case of long-chain (such as n-octyl) disulfides and diselenides.

A variety of unsymmetrical monosulfides can be synthesized in good yields by copper-catalyzed coupling of disulfides with organoboronic acids in air. Furthermore, this method can result in the successful aryl- or alkylation of both organosulfide groups in a disulfide. Georg Thieme Verlag Stuttgart.

A new cobalt-catalyzed coupling of aryl halides with thiophenols and alkanethiols is reported. A variety of aryl sulfides can be prepared in excellent yields under mild reaction conditions using 1-2 mol % of Col2(dppe) and Zn. This new cobalt-catalyzed coupling represents an interesting addition to previously known methods to synthesize thioethers.

Disclosed is an efficient and widely-applicable method for commercially producing a thioether compound or a thiol compound which is useful as a pharmaceutical product or a production intermediate of a pharmaceutical product. Specifically disclosed is a method for producing a thioether compound represented by the general formula [I] below or a salt thereof. This method is characterized in that a compound represented by the following general formula [III]: [III] (wherein X represents a bromine atom, a chlorine atom or a trifluoromethylsulfonyloxy group, and ring A represents an aryl group or a heteroaryl ring group) or a salt thereof is reacted with a thiol compound represented by the following general formula [II]: [II] or a salt thereof in the presence of a palladium compound such as Pd2(dba)3, a base such as i-Pr2NEt and a phosphorus compound represented by the following formula [AA].

(Chemical equation presented) We have developed an efficient palladium-catalyzed carbon-sulfur bond formation reaction of aryl bromides, triflates, and activated aryl chloride. Using this protocol, we have shown tolerance to a wide variety of aryl thiols and alkyl thiols that can also be used as sulfide equivalents.

Several drugs bearing the 4-phenoxyphenoxy skeleton and other closely related structures were designed, synthesized, and evaluated as antiproliferative agents against Trypanosoma cruzi, the etiologic agent of Chagas' disease. The new class of drugs was envisioned by modifying the nonpolar 4-phenoxyphenoxy moiety replacing selected aromatic protons by different groups via electrophilic aromatic substitution reactions as well as introducing a sulfur atom at file polar extreme. Of the designed compounds, sulfur-containing derivatives were shown to be potent antireplicative agents against T. cruzi. Among these drugs, 4-phenoxyphenoxyethyl thiocyanate (compound 56) proved to be an extremely active growth inhibitor of the epimastigote forms of T. cruzi and displayed an IC500 of 2.2 μM. Under the same assay conditions, this drug was much more active than Nifurtimox, one of the drugs currently in clinical use to control this disease. This thiocyanate derivative was also a very active inhibitor against the intracellular form of the parasite at the nanomolar level. Other sulfur derivatives prepared also exhibited very potent antiproliferative action against T. cruzi. The presence of a sulfur atom at the polar extreme for this family of compounds seems to be very important for biological action because this atom was always associated with high inhibition values. 4-Phenoxyphenoxyethyl thiocyanate presents very good prospective not only as a lead drug but also as a potential chemotherapeutic agent.

In the liquid phase at 125-215 deg C thiophenol only reacts effectively with 2- and 4-bromophenol, 1-bromo-2-napthol, 1-bromonapthalene, and 9-bromoanthracene, forming the corresponding phenyl aryl sulfides. 2-Thiophenethiol and 1-thionapthol reduce the same bromine derivatives to the corresponding arenes.The disulfides formed here undergo secondary transformations.The reactions of thiophenol with 2- and 4-bromophenol and 1-bromo-2-napthol are convenient preparative methods for the synthesis of the previously difficulty obtainable phenyl hydroxyaryl sulfides.

2,2′-, 2,4′- and 4,4′-Monothiobisphenol separately rearrange in phenol at 180° in the presence of sodium hydroxide to give similar mixtures containing only 2,2′-, 2,4′- and 4,4′-monothiobisphenol in the approximate ratio, 45:45:10. The rearrangements appear to be intermolecular and they are interpreted in terms of polar processes which lead initially to the formation of o- and p-monothiobenzoquinones. 2,2′-Dithiobisphenol, 4,4′-dithiobisphenol and 4,4′-trithiobisphenol under similar conditions are desulphurated with the evolution of hydrogen sulphide also to give mixtures containing only 2,2 - 2,4′- and 4,4′-monothiobisphenol whilst 3,3′-dithiobisphenol is stable in alkaline phenol even after long periods at 180°. Similar initial heterolyses to o- and p-monothiobenzoquinones are suggested as sources of the monothiobisphenols and displacements of sulphide- or hydrosulphide-ions from intermediate benzeneperthiolate ions by carbanions derived from phenol are suggested as sources of the hydrogen sulphide.

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