108-98-5

A new method for deprotection of thioesters using TiCl4/Zn at 0-25 deg C is described. The procedure chemoselectively cleaves the S-CO bond in thioesters in the presence of other carbonyl functional groups and other protecting groups to cleanly produce thiols.

Preparation methods of dibenzoxanthene derivatives are surveyed alongside the synthesis of some of the titled compounds, which are the sulfur analogues of dibenzoxanthenes. Our new procedure for the conversion of phenols to thiophenols was used to prove the structure of such sulfur analogues. Copyright Taylor & Francis Inc.

Human farnesyl pyrophosphate synthase (Homo sapiens FPPS, HsFPPS) is a target for treating bone resorption diseases and some cancers. HsFPPS is potently inhibited by bisphosphonates, but due to poor cell penetration and distribution in soft tissue, there is currently interest in the development of non-bisphosphonate inhibitors as cancer therapeutics. Here, we report the discovery and development of HsFPPS inhibitors based on the phenolic diterpene carnosic acid (CA), an antimicrobial found in rosemary and sage, which showed better cellular anticancer activities than the bisphosphonate drug zoledronate in pancreatic cancer cell lines, as well as an HsFPPS-dependent mechanism of action. Hit-to-lead optimization of CA improved HsFPPS inhibition by >100-fold. A slow dissociation inhibition pattern and a noncompetitive allosteric binding mode were found, and cellular mechanism-of-action studies showed that these inhibitors inhibit tumor cell growth primarily by inhibiting HsFPPS, leading to downregulation of Ras prenylation and cell apoptosis. The discovery of this series of compounds together with proof-of-mechanism in pancreatic cancer cells may pave the way for targeting HsFPPS in soft tissue cancers using natural-product-derived inhibitors.

Borylation of the C-S bond of diaryl sulfoxides with bis(pinacolato)diboron (B 2 pin 2) is accomplished by means of a phosphine-ligated palladium catalyst and LiN(SiMe 3) 2 as a base. Both of the aryl rings of the diaryl sulfoxides are converted into borylated products.

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A highly effective and mild deprotection method was developed for benzyl thioethers using dibutylmagnesium in the presence of a catalytic amount of titanocene dichloride. This methodology is applicable to both aromatic and aliphatic benzyl thioethers.

The reactions of O-ethyl S-phenyl dithiocarbonate (1) and O-ethyl S-(p-nitrophenyl dithiocarbonate (2) with a series of secondary alicyclic amines, namely, piperidine, piperazine, 1-(β-hydroxyethyl)piperazine, morpholine, 1-formylpiperazine, and (with 2 only) piperazinium ion, are subject to a kinetic study at several pH values.The reaction leads to the corresponding thiocarbamates and thiophenols (measured as thiophenoxide ion by UV-vis spectrophotometry).Pseudo-first-order rate coefficients (kobsd) are found throughout (amine excess).The kinetics are first order in amine for the reactions of 2.The plots of kobsd vs for the reaction of 1, except with 1-formylpiperazine, are linear, but near the origin they are curved, showing a more complex rate equation.The reaction of 1 with 1-formylpiperazine shows a second-order dependence on the amine.No dependence on pH of the second-order rate constant values is observed.The findings are well-accommodated by a mechanistic model involving reversible nucleophilic attack on the thiocarbonyl group, two tetrahedral intermediates, 3 and 4, and a deprotonation step.The Bronsted-type plots obtained are linear (β1 = 0.22) for the reaction of 1 and curved for 2 (β1 = 0.2 and β2 = 0.8).The Bronsted-type plot obtained with the rate constants for amine expulsion from 3 is linear with β-1 = -0.67 and -0.54 for the reactions of 1 and 2, respectively.

Vinylselenols and vinyltellurols have been prepared by slow addition of tributyltin hydride to the corresponding divinyldiselenide or divinylditelluride in tetraglyme.

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The difluoropropargyl group is a useful moiety for biological applications such as in vivo click chemistry for molecular imaging techniques. Silyl-protected bromodifluoropropyne is an important difluoropropargylation reagent with previously unexplored radical reactivity. Herein, we report visible-light-induced thiyl-radical-catalyzed hydrodifluoropropargylation reactions between silyl-protected bromodifluoropropyne and alkenes in the presence of benzothiazoline as a critical reductant. (Figure presented.).

Pd-PVP-Fe (palladium-poly(N-vinylpyrrolidone)-iron) nano catalyst catalyzes selective C–S cross-coupling (S-arylation) reactions of thiols with aryl halides and avoids the formation of S–S (disulfide) homocoupling byproducts. The reactions were carried out in aqueous media using only 0.23?mol% palladium with high selectivity and short reaction time. The effects of the Pd0and Fe0moieties on the C–S cross-coupling reaction mechanism, yield, and selectivity were investigated. The yield and selectivity can be controlled by adjusting the order of adding the reactants and catalyst into the reaction medium. The X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD) microscopy, energy dispersive X-ray (EDX) spectroscopy, and thermal gravimetric analysis (TGA) tools were used to characterize the catalyst. The C–S cross-coupling reaction process could be repeated up to six times without losing effectiveness. The metals leaching of Pd-PVP-Fe nanocatalyst after reusing cycles were investigated by atomic absorption spectroscopic (AAS) and EDX spectroscopy. The nature of Pd metal after the first run of the C–S cross-coupling reaction was studied by UV–vis spectrophotometry. The morphology of bimetallic nanocatalyst after the first run of the C–S cross-coupling reaction was investigated by SEM, EBSD, and EDX microscopy.

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A 3,3'-tetramethylene-bridged 4-methylthiazolium salt, in methanol containing o-methylbenzaldehyde and triethylamine or 1,5-diazabicycloundec-5-ene, catalyses the reduction of diphenyl disulphide and lipoamide to the corresponding thiols, with concomitant oxidation of o-methylbenzaldehyde to methyl o-methylbenzoate.

Phosphine oxides may be chemoselectively reduced to phosphines in excellent yield in the presence of several other functional groups using alane. An aqueous workup is not required.

Eight previously unreported phenyl arylsulfonyl-alkyl-dithiocarbamates were synthesized by treatment of arylsulfonamides with phenyl chlorodithioformate in an adaptation of a general amine acylation method. A kinetic investigation of their alkaline hydrolysis was performed and the experimental data are discussed. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.

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The triethylamine-catalyzed addition reactions of benzenethiol to 2-cyclopenten-1-one and its 2-and 3-methyl derivatives have been found to be appreciably reversible in chloroform solution. Rates and equilibria have been carefully measured at 25°C in order to assess the negative influence on addition exerted by methyl groups substituted on the carbon-carbon double bond. 2-Methyl-2-cyclopenten-1-one has been found to react with benzenethiol under kinetic control to give the cis adduct as the sole detectable product in a highly stereoselective anti addition process. However, on prolonged reaction times the system slowly evolved toward a new state of equilibrium in which the more stable trans adduct, derived from a syn addition mode, was the predominant isomer.

Rate and equilibria constants for the reactions of 3,6-bis(dimethylamino)xanthylium cation with several amines and thiolates in dimethyl sulfoxide solution have been measured.Assumptions used in previous work to estimate equilibrium constants in dimethyl sulfoxide solution are found to be incorrect.Conclusions reached from those assumptions are not supported by the present data, and there are no examples in the present or past work where solvent effects on rates are appreciably greater than those on the corresponding equilibria for simple bond-forming reactions.Equilibrium constants have also been determined for the reactions of thiophenoxide and trifluoroethoxide ions with (p-(dimethylamino)phenyl)tropylium ion in water.The kinetic reactivities of trifluoroethoxide relative to hydroxide ion and of thiophenoxide relative to alkanethiolates are much greater than the corresponding equilibrium reactivities.In addition, an example of a slow, rate-determining, proton transfer in the reaction of morpholine with 3,6-bis(dimethylamino)xanthylium cation in dimethyl sulfoxide has been found.

A novel method for the Cu(OAc)2 catalyzed synthesis of unsymmetrical sulfides from triphenyltin chloride and aryl halides using S8 as the sulfur source in PEG200 at 60-80°C is reported. Triphenyltin chloride is capable of delivering all of its phenyl groups to the product. Also, the copper catalyzed synthesis of symmetrical diaryl sulfides from aryl halides using S8 is described.

Second-order rate constants (kN) for the nucleophilic reactions of piperidine, morpholine, piperazine, and N-substituted piperazines with the title substrates are reported in water, at 25 deg C, ionic strength 0.2 M (maintained with KCl).The Broensted-type plot obtained for the aminolysis of phenyl thiolacetate is linear while that for the p-nitrophenyl derivative (NPTA) is curved, with the center of curvature at pKa=10.5 (pKa0).According to these results the most likely mechanism involves a zwitterionic tetrahedral intermediate (T+/-), for which decomposition to products is the rate-limiting step for all the reactions, except that of NPTA with piperidine.For this reaction the formation of T+/- is rate determining.A semiempirical equation based on the above hypothesis accounts for the Broensted-type curve obtained in the aminolysis of NPTA.Estimation of the microscopic rate constants involved, in a possible more general reaction scheme and evaluation of the pKa's of T+/- indicate that expulsion of the leaving group of the substrate from T+/- is faster than deprotonation of T+/- by a base, precluding therefore the formation of an anionic tetrahedral intermediate.The fact that pKa0=10.5 for the NPTA reactions means that an (hypothetical) amine of pKa=10.5 leaves T+/- as readily as p-nitrothiophenoxide ion (pKa=4.6).From these and other data it is calculated that the nucleofugality from T+/- of an amine of pKa=4.6 is ca. 3*104 times larger than that of p-nitrothiophenoxide ion.The estimated pKa0 values for the aminolysis of (hipothetical) aryl acetates with leaving groups of pKa=4.6 and 6.5 (the same pKa as thiophenol) are pKa0=8.0 and 9.0, respectively, which gives nucleofugality ratios (a given amine/aryl oxide ion) from the oxy T+/- smaller than those from the corresponding sulfur T+/-.It is claimed that expulsion of ArS- from T+/- is only slightly slower than that of an isobasic ArO- from the oxy T+/-.Therefore, the above results indicate that the "push" provided by ArS in T+/- to expel a given amine is much stronger than that exerted by an isobasic ArO in the oxy T+/-.Activation parameters are reported for the reactions of the title substrates with piperidine, piperazine, and N-formylpiperazine.

Surface plasmon plays an important role in surface catalysis reactions, and thus the tuning of plasmon on metal nanostructures and the extension of plasmon induced surface catalysis reactions have become important issues. Au nanoparticle monolayer film was fabricated by the assembling of Au nanoparticles at the liquid-air interface with numerous hot spots for strong surface plasmon coupling. A facile approach was developed to achieve the decarboxylation reaction driven by appropriate surface plasmon on the Au nanoparticle monolayer film surface, and surface enhanced Raman spectroscopy (SERS) has been developed as a sensitive tool for the in situ monitoring of the plasmon induced surface reaction. The effects of the power and wavelength of the laser and solution pH on the decarboxylation reaction were investigated. With laser illumination, para-mercaptobenzoic acid (PMBA) was transformed to thiophenol (TP), and the decarboxylation was enhanced on increasing the laser power and illumination time. The results revealed that the carboxylate groups of the adsorbed PMBA molecules were removed to produce TP, which were still adsorbed onto Au surfaces. The solution pH values exhibited a significant influence on the decarboxylation reaction. In air and neutral solution, decarboxylation proceeded at a slow rate to transform PMBA to TP, while it was absent in acidic solution. The deprotonated carboxylate group accelerated the decarboxylation for producing TP with a fast rate in alkaline solution. As a comparison, a similar plasmon driven decarboxylation reaction was observed on a Ag nanoparticle monolayer film surface. These results suggested that the transformation from PMBA to TP molecules on an Au nanoparticle film surface under laser illumination was associated with a surface-catalyzed reaction driven by local surface plasmon.

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An efficient and transition-metal-free approach for the synthesis of 4-arylquinolines from readily available anilines and alkynes in the presence of K2S2O8 and DMSO has been developed. A variety of alkynes and anilines having a diverse range of substitution patterns can undergo the one-pot cascade process successfully. Effectively, this method uses DMSO as one carbon source, thus providing a highly atom-economical and environmentally benign approach for the synthesis of 4-arylquinolines.

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Diaryl thioethers can be prepared via a copper-catalyzed cross-coupling between aryl halides and thioacetamide using Cs2CO3 as a base and DMSO-H2O as a solvent at 120 °C. Georg Thieme Verlag Stuttgart - New York.

Hydrogen sulfide is an important biological signaling molecule and an important environmental target for detection. A major challenge in developing H2S detection methods is separating the often similar reactivity of thiols and other nucleophiles from H2S. To address this need, the nucleophilic aromatic substitution (SNAr) reaction of H2S with electron-poor aromatic electrophiles was developed as a strategy to separate H2S and thiol reactivity. Treatment of aqueous solutions of nitrobenzofurazan (7-nitro-1,2,3-benzoxadiazole, NBD) thioethers with H 2S resulted in thiol extrusion and formation of nitrobenzofurazan thiol (λmax = 534 nm). This reactivity allows for unwanted thioether products to be converted to the desired nitrobenzofurazan thiol upon reaction with H2S. The scope of the reaction was investigated using a Hammett linear free energy relationship study, and the determined ρ = +0.34 is consistent with the proposed SN2Ar reaction mechanism. The efficacy of the developed probes was demonstrated in buffer and in serum with associated submicromolar detection limits as low as 190 nM (buffer) and 380 nM (serum). Furthermore, the sigmoidal response of nitrobenzofurazan electrophiles with H2S can be fit to accurately quantify H2S. The developed detection strategy offers a manifold for H2S detection that we foresee being applied in various future applications.

Classic acetyl thioester protection/deprotection methodologies are widely used in organic synthesis, but deprotection step usually requires harsh conditions not suitable for labile substrates. In this work, a new method for thioester deprotection using a thiotransesterification approach is described. Firstly, thioglycolic acid (TGA) was identified as a good deprotecting reagent in solution. In order to develop a thiol polymer-supported reagent, TGA was anchored to a PEG-based resin through an amide bond (TG-NCO-SH). Both homogeneous and heterogeneous approaches were conveniently carried out at room temperature, in aqueous buffer at pH 8. The mild conditions were suitable for alkyl and phenyl thioesters. Moreover labile thioesters containing thiazolidine and oxazolidine scaffolds, bearing amine, ester and acetal functionalities were also deprotected. The polymer-supported TGA gave better deprotection yields compared to TGA in solution, yields ranging from 61 to 90%. The feasibility of the recovery and reuse of TG-NCO-SH reagent was explored, showing it can be reused at least five times without lossing the activity.

The invention provides a method for selectively removing benzyl, allyl and propargyl protecting groups by visible light or near visible light, namely a substrate containing benzyl, allyl or propargyl protecting groups. The method has the advantages of simple operation, safe and clean visible light or near visible light as excitation conditions, cheap and easily available reagents, high reaction yield, high reaction chemistry and regional selectivity, and is suitable for selective removal of benzyl, allyl and propargyl protecting groups in various substrates.

Organo disulfides represent an abundant class of compounds in chemical biology, pharmaceutical fields, and industry. They are traditionally synthesized by the oxidation of mercaptan in the presence of an organic ligand supported metal catalyst or toxic oxidants under harsh conditions. Here, we disclose a highly-efficient pathway in which disulfide is synthesized by organic boric acid and Na2S2O3 using the catalyst (NH4)3[CrMo6O18(OH)6], demonstrating a high activity and excellent selectivity. Various boric acid derivatives have been successfully transformed into the corresponding disulfides. Mechanistic insights have been furnished based on the observation of intermediate and control experiments.

Herein, a novel heterogeneous nanoscale reducing agent for antibody cleavage, made of iron oxide nanoparticles, silica network, palladium on calcium carbonate (10%), and dithiothreitol (Fe3O4?Pd/CaCO3-DTT), is presented as a substantial alternative for traditional homogeneous analogues. Conventionally, antibody fragmentation is accomplished using reducing agents and proteases that digest or cleave certain portions of the immunoglobulin protein structure to provide active thiol sites for drug tagging aims. Then, dialysis process is needed to separate excess chemical structures and purify the reduced antibody. In this work, we have made an effort to design a suitable heterogeneous tool for protein cleavage and skip the dialysis process for purification of the reduced antibody. In this regard, firstly, various preparation methods including microwave irradiation, reflux and ultrasonication have been precisely compared, and it has been proven that the best result is obtained through 10 min ultrasound (US) irradiation using an US bath with 50 KHz frequency and 200 W L?1 power density. Then, all the necessary structural analyses have been done and thoroughly interpreted for the final product. Afterward, the catalytic performance of Fe3O4?Pd/CaCO3-DTT nanoscale system in the presence of US waves (50 KHz, 200 W) has been monitored using some disulphide derivatives. The NPs could be conveniently separated from the mixture through their substantial paramagnetic property. Thus, dialysis process in which various types of membranes are used is practically jumped after the reduction process. In this work, this is clearly demonstrated that there is a constructive synergistic effect between US waves and prepared Fe3O4?Pd/CaCO3-DTT nanoscale reducing agent. Ultimately, trastuzumab (anti HER-2) antibody has been used to test the performance of the prepared Fe3O4?Pd/CaCO3-DTT NPs in a real protein reduction reaction.

An operationally simple mechanochemical C-S coupling of aryl halides with thiols has been developed. The reaction process operates under benchtop conditions without the requirement for a (dry) solvent, an inert atmosphere, or catalyst preactivation. The reaction is finished within 3 h. The reaction is demonstrated across a broad range of substrates; the inclusion of zinc metal has been found to be critical in some instances, especially for coupling of alkyl thiols.

We describe a three-component reaction of o-iodoanilines with K2S and DMSO that provides 2-unsubstituted benzothiazoles in moderate to good isolated yields with good functional group tolerance. Electron-rich aromatic amines and o-phenylenediamines instead of o-iodoanilines provided 2-unsubstituted benzothiazoles and 2-unsubstituted benzimidazoles with and without K2S under similar conditions. Notably, DMSO plays three vital roles: carbon source, solvent, and oxidant.

Direct hydrogenation of thioesters with H2 provides a facile and waste-free method to access alcohols and thiols. However, no report of this reaction is documented, possibly because of the incompatibility of the generated thiol with typical hydrogenation catalysts. Here, we report an efficient and selective hydrogenation of thioesters. The reaction is catalyzed by an acridine-based ruthenium complex without additives. Various thioesters were fully hydrogenated to the corresponding alcohols and thiols with excellent tolerance for amide, ester, and carboxylic acid groups. Thiocarbamates and thioamides also undergo hydrogenation under similar conditions, substantially extending the application of hydrogenation of organosulfur compounds.

The invention discloses a novel synthesis method for a thiophenol derivative, and belongs to the technical field of synthesis. The method comprises the steps that a diphenyl sulfide derivative of thegeneral formula II and hydrogen sulfate are adopted as raw materials, a tubular reactor is used as a reactor, and an equimolar quantitative reaction is performed under the normal pressure and the temperature of 330-350 DEG C to synthesize the thiophenol derivative of the general formula I. By adopting the method, the raw material utilization rate can reach 100%, no solvent or catalyst needs to beadopted in the reaction, the reaction temperature is low, and the product yield and purity are high.

A four-step synthesis of benzo- and naphthothiophenes that have biological importance and application in material science was integrated into a one-pot reaction by using silica gel-supported acid and base reagents, NaHSO 4 /SiO 2 and Na 2 CO 3 /SiO 2. The supported reagents provided acid and base environments on the surface of the supports without neutralization and worked separately in the same medium. The four-step reaction comprises (i) deacetylation of 3-halo-2,4-pentanediones to α-halo ketones, (ii) deacetylation of S -aryl thioacetates to arenethiols, (iii) coupling of α-halo ketones and arenethiols to give α-sulfanyl ketones, and (iv) cyclization of sulfanyl ketones to benzo- and naphthothiophenes. The steps (i) and (iii) proceeded by Na 2 CO 3 /SiO 2, and (ii) and (iv) by NaHSO 4 /SiO 2. The four-step reaction proceeded efficiently by introduction of starting materials and reagents in a single reaction vessel. The starting materials were very easy to handle and unpleasant smell of aryl thiols that were used in conventional methods could be avoided. Novel thirty-nine benzo- and naphthothiophenes were synthesized by this method in excellent to fair yields.

A new oxidative [2+2+1] heteroannulation of 1,7-enynes with disulfanes promoted by Et3N, producing 3,3a-dihydro-thieno[3,4-c]quinolin-4(5H)-ones, is described. This reaction is achieved by using equivalent amounts of 1,7-enynes, sulfur atoms (disulfanes), tert-butyl peroxybenzoate (TBPB) as an oxidant and Et3N as the base, and represents an unprecedented strategy to applications of disulfanes as sulfur atom sources in synthesis. (Figure presented.).

To expand the toolbox of dynamic covalent and systems chemistry, we investigated the acid-catalyzed exchange reaction of trithioorthoesters with thiols. We found that trithioorthoester exchange occurs readily in various solvents in the presence of stoichiometric amounts of strong Bronsted acids or catalytic amounts of certain Lewis acids. The scope of the exchange reaction was explored with various substrates, and conditions were identified that permit clean metathesis reactions between two different trithioorthoesters. One distinct advantage of S, S, S-orthoester exchange over O, O, O-orthoester exchange is that the exchange reaction can kinetically outcompete hydrolysis, thereby making the process less sensitive to residual moisture. We expect that the relatively high stability of the products might be beneficial in future supramolecular receptors or porous materials.

Organosulfur compounds are ubiquitous in synthetic chemistry, biology and materials chemistry. The reactivity of free sulfhydryls requires their masking in many synthetic strategies. To facilitate the isolation of protected thiols by chromatography, we propose 2-(3-cyanopropyldimethylsilyl)ethyl as a polar protecting group analogue of 2-(trimethylsilyl)ethyl. The masked thiophenol is obtained in two synthetically complementing ways. Either an existing thiophenol is protected, or the protected thiol group is introduced by a cross-coupling reaction. In both cases the required reagents are readily available from inexpensive starting materials. Thiol protection and thiol introduction both tolerate a large variety of functional groups and substitution patterns, and the protected thiophenols are stable toward a broad range of reaction conditions. The stability of the protected derivatives in cross-coupling reactions and the mild reaction conditions for the release of the protecting group further emphasizes the potential of the methodology.

A selective four-electron reduction of CO2 with thiophenol using NaBH4 as a reductant is described to access dithioacetals. This reaction provides a novel synthetic method for the highly selective conversion of CO2 into methylene, and a new access to molecular structures via formation of C-S bonds using CO2 as the C1 source.

We report an additive-free, base-catalyzed C-, N-, O-, and S-Si bond cleavage of various organosilanes in mild conditions. The novel catalyst system exhibits high efficiency and good functional group compatibility, providing the corresponding products in good to excellent yields with low catalyst loadings. Overall, this transition-metal-free process may offer a convenient and general alternative to current employing excess bases, strong acids, or metal-catalyzed systems for the protodesilylation of organosilanes.

Under catalyst-free and additive-free conditions, a novel, convenient, eco-friendly method for the synthesis of benzothiazolethiones has been developed. The three-component reaction of o-iodoanilines and K2S with DMSO proceeded smoothly and the corresponding benzothiazolethiones were obtained with good isolated yields. Meanwhile, this method could be used for the synthesis of thioureas from primary diamines. Furthermore, mechanism research showed that DMSO not only functioned as a carbon source, but also as a mild oxidant in this reaction.

The invention provides a method for preparing sulfhydryl compounds by hydroxyl substitution and the sulfhydryl compounds. According to the method, low-cost and easily-obtained benzene or fused ring compounds with phenolic hydroxyl groups or benzyl hydroxyl substituents serving as raw materials to react with the raw materials such as inorganic sulfide under the catalysis conditions to prepare the corresponding sulfhydryl compounds. The method has the advantages that the preparation method is simple, convenient and rapid, low in cost, mild in reaction condition, high in reaction site selectivity and high in yield, a post-processing process is simple, and no pollution is caused.

Hydropersulfides (RSSH) are formed endogenously via the reaction of the gaseous biotransmitter hydrogen sulfide (H2S) and disulfides (RSSR) and/or sulfenic acids (RSOH). RSSH have been investigated for their ability to store H2S in vivo and as a line of defense against oxidative stress, from which it is clear that RSSH are much more reactive to two-electron oxidants than thiols. Herein we describe the results of our investigations into the H-atom transfer chemistry of RSSH, contrasting it with the well-known H-atom transfer chemistry of thiols. In fact, RSSH are excellent H-atom donors to alkyl (k ～ 5 × 108 M-1 s-1), alkoxyl (k ～ 1 × 109 M-1 s-1), peroxyl (k ～ 2 × 106 M-1 s-1), and thiyl (k > 1 × 1010 M-1 s-1) radicals, besting thiols by as little as 1 order and as much as 4 orders of magnitude. The inherently high reactivity of RSSH to H-atom transfer is based largely on thermodynamic factors; the weak RSS-H bond dissociation enthalpy (～70 kcal/mol) and the associated high stability of the perthiyl radical make the foregoing reactions exothermic by 15-34 kcal/mol. Of particular relevance in the context of oxidative stress is the reactivity of RSSH to peroxyl radicals, where favorable thermodynamics are bolstered by a secondary orbital interaction in the transition state of the formal H-atom transfer that drives the inherent reactivity of RSSH to match that of α-tocopherol (α-TOH), nature's premier radical-trapping antioxidant. Significantly, the reactivity of RSSH eclipses that of α-TOH in H-bond-accepting media because of their low H-bond acidity (α2H ～ 0.1). This affords RSSH a unique versatility compared to other highly reactive radical-trapping antioxidants (e.g., phenols, diarylamines, hydroxylamines, sulfenic acids), which tend to have high H-bond acidities. Moreover, the perthiyl radicals that result are highly persistent under autoxidation conditions and undergo very rapid dimerization (k = 5 × 109 M-1 s-1) in lieu of reacting with O2 or autoxidizable substrates.

The invention relates to a method for synthesizing thiophenol from hydrogen sulfide and chlorobenzene in a channelization reactor. Particularly, chlorobenzene and hydrogen sulfide are mixed in an autoclave, mixed liquor is pumped into the channelization reactor through a metering pump, and a sulfhydrylation reaction is carried out under oil bath heating. The molar ratio of chlorobenzene to hydrogen sulfide is 1:1 to 1:10, the reaction pressure ranges from 10 MPa to 25 MPa, the reaction temperature ranges from 120 DEG C to 300 DEG C, and the reaction time ranges from 10 mins to 180 mins. After the reaction is completed, alkali liquor absorbs light components in the reaction system, a reaction mixture is washed with deionized water, an oil phase is collected and directly subjected to reduced pressure distillation, and fractions (10 mmHg and 47-49 DEG C) are collected.

The invention relates to a phenthiol synthesis method, in particular to a method comprising the following steps that in a high-pressure reaction vessel, hydrogen sulfide takes a contact reaction with chlorobenzene in a supercritical state, wherein the mol ratio of the chlorobenzene to the hydrogen sulfide is 1:1 to 1:10, the reaction temperature is 100 DEG C to 200 DEG C, the reaction pressure is 9 to 25 MPa, and the reaction time is 1 to 10 hours; after the reaction is completed, water is used for washing a reaction mixture; an oil phase is collected; reduced pressure distillation is performed; fraction (10mmHg, 47 to 49 DEG C) is collected; the phenthiol is obtained.

A highly porous metal–organic frame work Cu3 BTC2 (copper(II)-benzene-1,3,5-tricarboxylate) that is known as MOF-199 was synthesized from the reaction of 1,3,5-benzenetricarboxylic acid and Cu(OAc)2·H2O by a solvothermal method and characterized by several techniques including FT-IR, XRD, EDX and scanning electron microscopy. The MOF-199 used as an efficient catalyst for one-pot synthesis of thiols by domino reactions of aryl halides and thiourea, and subsequently conversion to aryl alkyl sulfides and diaryl disulfides in polyethylene glycols (PEGs). A variety of aryl alkyl sulfides can be obtained in good to excellent yields in a relatively short reaction time and in the presence of the trace amount of catalyst. Also, the catalyst can be separated from the reaction mixture by decanting, and be reused without significant degradation in catalytic activity.

The reversible ring-opening addition and fragmentation reaction of p-cresol-based N-phenylbenzoxazine with aliphatic and aromatic thiols was investigated in solvent-mediated and solvent-free reactions. Independently of the used thiol, N-phenylbenzoxazine and the thiols reacted to equilibrium with comparable amounts of reactants and products in aprotic solvent, whereas in protic solvent almost full conversions were reached. In contrast, thiol reactivity was a crucial factor in solvent-free reactions yielding fast and complete conversions for a more acidic thiol and balanced equilibrium concentrations in case of thiols with high pKa values. The strong influence of thiols with low pKa values emphasizes the relevance of the protonation step in the ring-opening reactions of 1,3-benzoxazines with thiols in absence of solvents where acidity predominates nucleophilicity. The reverse reactions, namely adduct dissociation and benzoxazine recovery, were successfully conducted at elevated temperatures and reduced pressure facilitated by the removal of the formed thiols yielding up to 95% recovered 1,3-benzoxazine. These results provide deeper understanding of the reversible ring-opening reaction mechanism of 1,3-benzoxazine with thiols.

In this paper, we report a method for the conversion of primary carbamates into thiols in the presence of phosphorus pentasulfide (P 2 S 5) in refluxing toluene. Presently, no method exists in the literature for conversion of carbamates into thiols and, to the best of our knowledge, it is the first report for this type of conversion. This method presents an indirect route for the conversion of alcohols into thiols via their carbamate derivatives that may be useful in the total synthesis of compounds containing a thiol functionality.

P-S bond formation/cleavage mediated by a nickel ion supported by a PPP ligand (PPP = P[2-PiPr2-C6H4]2-) has been investigated herein. To gain an entry into this chemistry, a mononuclear thiolato nickel complex, (PPP)Ni(SAr) (1a,b) was prepared by treating the chloride starting material with NaSPh. Upon carbonylation, this complex produces a nickel(0) monocarbonyl species, (PPSArP)Ni(CO) (2a,b), in which the thiolate migrates onto the central P of the ligand to give a P-S bond and two-electron reduction of a nickel(II) center. The reaction undergoes via a pseudo-first-order decay with respect to consumption of a nickel(II) thiolato species, suggesting an intramolecular reaction under the excess CO(g) conditions. The reverse reaction involving P-S bond cleavage with concomitant decarbonylation occurs to regenerate 1a,b in benzene. Reaction of 2a with trityl chloride results in Ph3CSPh formation, whereas the reaction with MeI gives methylation at a phosphide moiety or a thiolate group.

In this paper, we report hemithioketal formation of diphenylpropanetrione (DPPT) with thiols and their recovery. Addition of thiols to the central carbonyl group occurred readily at ambient temperature to provide the thiol adducts of DPPT (DPPT–thiols), which has a hemithioketal structure. On the other hand, oxidizing DPPT–thiols with an oxidation reagent enabled successful recovery of DPPT, which indicated the reversible nature of this system.

PROBLEM TO BE SOLVED: To provide a method of production, obtaining a thiol compound in a high yield by using a hydroxy compound and hydrogen sulfide as raw materials. SOLUTION: This method of production includes reacting the hydroxy compound with hydrogen sulfide in the presence of a metal oxide catalyst selected from a complex metal oxide containing zirconia, acid-carrying zirconia or silica/titania having mesoporous pores, under gas phase heating, and it is especially useful for the production of an aromatic thiol compound such as thiophenol. COPYRIGHT: (C)2011,JPOandINPIT

Tris(3-hydroxypropyl)phosphine (THPP) is demonstrated to be a versatile, water-soluble and air-stable reducing agent, allowing for the rapid, irreversible reductive cleavage of disulfide bonds in both aqueous and buffered aqueous-organic media. The reagent shows exceptional stability at biological pH under which condition it permits the rapid reduction of a wide range of differentially functionalized small-molecule disulfides.

A general, practical, and efficient method for the dimerization of dithiocarbamates has been developed that can be used to prepare the corresponding bis(1-arylimino-1-alkyl/ arylthiomethyl) disulfides with dilauroyl peroxide (DLP) as mild oxidant. Notably, a lauroyl radical, rather than an undecyl radical, was established as the radical hydrogen-ab- stractor during the dimerization process. The amount of DLP impacts the dimerization yield, with 50 mol-% DLP giving the disulfides in the highest yields. The use of an excess of DLP generates the undecyl radical, which decomposes the disulfides rapidly to the corresponding isothiocyanates.

Leinamycin (LNM) is a sulfur-containing antitumor antibiotic featuring an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2- dithiolane moiety is essential for LNM's antitumor activity, by virtue of its ability to generate an episulfonium ion intermediate capable of alkylating DNA. We have previously cloned and sequenced the lnm gene cluster from Streptomyces atroolivaceus S-140. In vivo and in vitro characterizations of the LNM biosynthetic machinery have since established that: (i) the 18-membered macrolactam backbone is synthesized by LnmP, LnmQ, LnmJ, LnmI, and LnmG, (ii) the alkyl branch at C-3 of LNM is installed by LnmK, LnmL, LnmM, and LnmF, and (iii) leinamycin E1 (LNM E1), bearing a thiol moiety at C-3, is the nascent product of the LNM hybrid nonribosomal peptide synthetase (NRPS)-acyltransferase (AT)-less type I polyketide synthase (PKS). Sulfur incorporation at C-3 of LNM E1, however, has not been addressed. Here we report that: (i) the bioinformatics analysis reveals a pyridoxal phosphate (PLP)-dependent domain, we termed cysteine lyase (SH) domain (LnmJ-SH), within PKS module-8 of LnmJ; (ii) the LnmJ-SH domain catalyzes C-S bond cleavage by using L-cysteine and L-cysteine S-modified analogs as substrates through a PLP-dependent β-elimination reaction, establishing L-cysteine as the origin of sulfur at C-3 of LNM; and (iii) the LnmJ-SH domain, sharing no sequence homology with any other enzymes catalyzing C-S bond cleavage, represents a new family of PKS domains that expands the chemistry and enzymology of PKSs and might be exploited to incorporate sulfur into polyketide natural products by PKS engineering.

Herein, we have developed a mild and selective reductive deprotection method for the MAc protected alcohols using sodium borohydride. The new deprotection conditions provide a complete orthogonality between O-MAc and other protecting groups such as tert-butyl ester, N-Boc, Fmoc, Cbz, O-TBDMS, N-benzyl, O-benzyl, O-acetyl, N-acetyl, N-MAc, etc. In addition to O-MAc deprotection, this method is also applicable for S-MAc deprotection.

A copper-catalyzed chalcogenation of arylboronic acids with elemental sulfur or selenium is established, which provides diaryl disulfides or diaryl monoselenides in moderate to good yields with excellent selectivities, respectively. Moreover, after sequential reduction and coupling with aryl/alkyl iodides in one pot, unsymmetrical monosulfides were obtained in good yields.

The three-component reaction of aryl halides, sodium sulfide pentahydrate (Na2S×5 H2O), and propiolic acid in the presence of 2.5% bis(triphenylphosphine)palladium chloride [Pd(PPh3) 2Cl2], 5% 1,4-bis(diphenylphosphino)butane (dppb) and 2equivalents of 1,8-diazabicycloundec-7-ene (DBU) produces stereoselectively (Z)-3-arylthioacrylic acids in good yields. A study of the reaction pathway suggested that the C-S bond formation between aryl halides and Na 2S×5 H2O proceeded first, and the resulting intermediate reacted with propiolic acid to produce the desired product. In addition, when the resulting product was treated with acid, the respective thiochromenones were formed in good yields. Copyright

The chromium(III) tris-o-semiquinolate complex Cr(LSQ) 3 (LSQ is 3,6-di-tert-butyl-o-semiquinone) and the monoanionic paramagnetic nickel(II) complex [n-Bu4N][Ni(L S SQ)(L S DT)] (L S SQ is o-thiosemiquinone, L S DT is benzene-1,2-dithiolate) are considered as electromediators of hydrogen sulfide oxidation in the presence of various organic substrates (hex-1-ene, oct-1-ene, benzene, toluene, and benzoic acid). It is revealed that the electrolysis of hydrogen sulfide at the oxidation potential of the mediators in the presence of the substrates affords the corresponding aliphatic and aromatic thiols in a yield of 62-75%.

Redox-inactive metal ions have been recognized to be able to participate in redox metal-ion-mediated biological and chemical oxidative events; however, their roles are still elusive. This work presents how the redox-inactive metal ions affect the oxidative reactivity of a well-investigated manganese(II) with its corresponding manganese(IV) complexes having cross-bridged cyclam ligand. In dry acetone, the presence of these metal ions can greatly accelerate stoichiometric oxidations of triphenylphosphine and sulfides by the manganese(IV) complexes through electron transfer or catalytic sulfoxidations by the corresponding manganese(II) complexes with PhIO. Significantly, the rate enhancements are highly Lewis-acid strength dependent on added metal ions. These metal ions like Al3+ can also promote the thermodynamic driving force of the MnIV-OH moiety to facilitate its hydrogen abstraction from ethylbenzene having a BDECH value of 85 kcal/mol, while it is experimentally limited to 80 kcal/mol for MnIV-OH alone. Adding Al3+ may also improve the manganese(II)-catalyzed olefin epoxidation with PhIO. However, compared with those in electron transfer, improvements in hydrogen abstraction and electron transfer are minor. The existence of the interaction between Lewis acid and the manganese(IV) species was evidenced by the blue shift of the characteristic absorbance of the manganese(IV) species from 554 to 537 nm and by converting its EPR signal at g = 2.01 into a hyperfine 6-line signal upon adding Al3+ (I = 5/2). Cyclic voltammograms of the manganese(IV) complexes reveal that adding Lewis acid would substantially shift its potential to the positive direction, thus enhancing its oxidizing capability.

The enzyme thioredoxin reductase (TrxR) is attracting much interest as a potential target for cancer therapy. The presence of a selenium atom in the catalytic site makes it sensitive to inhibition by electrophilic molecules, including the AuI complex auranofin [2,3,4,6-tetra-O-acetyl-1-thio- β-D-glucopyranosato-S-(triethylphosphane)gold]. The reactions between auranofin and models of thiol and selenol nucleophiles present in TrxR (PhSH and PhSeH) have been investigated in chloroform and methanol by means of 1H, 31P, and 77Se NMR spectroscopy. In chloroform, auranofin undergoes ligand substitution of the tetraacetylthioglucose moiety by a PhS or PhSe group. The reaction is reversible in both cases, but it is characterized by widely different equilibrium constants (ca. 1 for S and at least 103 for Se). In polar solvents, such as methanol, the reaction is more complex, and the phosphane moiety also undergoes ligand exchange. Some features have been clarified through the investigation of Et3PAuCl. The elementary processes involved have been characterized by DFT calculations. Copyright

A new method to reduce aryl sulfo compounds via transfer hydrogenation was investigated, using Pd/C as a catalyst, and 2-propanol or formic acid as hydrogen sources. This new process is simple and clean.

In this work, at first, triazenes were synthesized from primary aryl amines. Afterwards, triazenes were converted into the corresponding thiophenols in one-pot using sodium sulfide in acidic media, by in situ generation of diazonium counterion beside hydrogen sulfide as anionic sulfur nucleophile at room temperature. The procedure can be a convenient shortcut for the preparation of thiophenols from primary aryl amines. Georg Thieme Verlag Stuttgart · New York.

The bis(triflimide)iron(III) salt catalyzes the hydrothiolation of styrenes in a Markovnikov fashion with good selectivities and high yields. After isolation, different benzylic thioethers are obtained. This iron(III) catalyst is unique in terms of regioselectivity and represents a sustainable and economic alternative to those processes based on stoichiometric reagents. Copyright

A new method is described for the oxidative chlorination of thiols to sulfonyl chlorides using titanium tetrachloride in combination with the oxidant hydrogen peroxide. Direct conversion of thiols into their corresponding thiosulfonates is also reported. Good to excellent yields, short reaction times, high efficiencies, cost-effectiveness, and, facile isolation of the desired products make the present methodology a practical alternative.

A mild and efficient method for the selective hydrolysis of 4-picolyl esters with magnesium in methanol or water in the presence of other esters and sensitive protecting groups is described. 4-Picolyl aryl ethers and thioethers are also smoothly deprotected to give the corresponding phenols and thiophenols. Georg Thieme Verlag Stuttgart. New York.

Otherwise sluggish or completely ineffective radical reductions of alkyl and aryl halides by N-heterocyclic carbene boranes (NHC-boranes) are catalyzed by thiols. Reductions and reductive cyclizations with readily available 1,3-dimethylimidazol-2-ylidene borane and a water-soluble triazole relative are catalyzed by thiophenol and tert-dodecanethiol [C9H 19C(CH3)2SH]. Rate constants for reaction of the phenylthiyl (PhS?) radical with two NHC-boranes have been measured to be ～108 M-1 s-1 by laser flash photolysis experiments. An analysis of the available evidence suggests the operation of polarity reversal catalysis.

CuI-nanoparticles-catalyzed selective synthesis of phenols, anilines, and thiophenols from aryl halides was developed in the absence of both ligands and organic solvents. Anilines were formed selectively with ammonia competing with hydroxylation and thiophenols were generated selectively with sulfur powder after subsequent reduction competing with hydroxylation and amination.