Benzyl Mercaptan Research Articles

Tetra Butyl Ammonium Bromide Catalyzed Synthesis of Thiols and Thioethers

A simple and commercially feasible route of synthesis of thiols and thioethers was developed using a simple phase transfer catalyst, i.e., Tetra Butyl Ammonium Bromide (TBAB). Sodium hydrogen sulfide (NaSH) is used as a sulfurization agent which is easily available and cost-effective. Thiols are obtained by treating alkyl or benzyl halides with sodium hydrogen sulfide (NaSH) in the presence of a phase transfer catalyst (TBAB) at 10 to 15℃. Thioethers are obtained by benzyl thiols treated with corresponding benzyl halides in the presence of a phase transfer catalyst (TBAB) at 10 to 15℃. Synthesis of thiols and thioethers is achieved by substitution reaction of benzyl or alkyl halides with sulfide in the presence of phase transfer catalyst (TBAB) and monochlorobenzene as a solvent at 10 to 15℃. Milder reaction conditions, excellent yield, shorter reaction time and operational simplicity are the key features of this procedure.

Desulfurization of Thiols for Nucleophilic Substitution.

Although the desulfurization of thiols is a topic of great importance and has received significant attention, most efforts have focused on the hydrodesulfurization of thiols. In this work, we describe the desulfurization of thiols for nucleophilic substitution. This process occurs rapidly, promoted by the Ph3P/ICH2CH2I system, and can be extended to a wide range of nucleophiles. Notably, free amines can be employed as nucleophiles to synthesize various secondary and tertiary amines. This method tolerates a wide array of functional groups, including hydroxyl groups in amination reactions. Benzyl thiols are particularly reactive and can be completely converted at room temperature within 15 min. Although alkyl thiols show lower reactivity, they can also be converted smoothly at a reaction temperature of 70 °C overnight.

Photoinduced Radical Desulfurative C(sp3)-C(sp2) Coupling via Electron Donor-Acceptor Complexes.

Herein, we disclose a radical desulfurative C-C coupling protocol for the synthesis of 4-alkylpyridines. A variety of substituents on both benzyl thiols and 4-cyanopyridines are tolerated. The reaction is carried out under mild and photocatalyst- and transition-metal-free conditions. Preliminary mechanistic studies show that an electron donor-acceptor complex is formed between benzyl thiols and 4-cyanopyridines under alkaline conditions. Then, a variety of 1°, 2°, and 3° C(sp3)-centered radicals was formed by cleavage of the C-S bond, and the 4-alkylpyridines were achieved through a radical-radical coupling with the pyridyl radical anion.

Synthesis, antioxidant and structural properties of modified ebselen derivatives and conjugates.

Ebselen is a drug in clinical trials for several diseases and degenerative conditions where oxidative stress is implicated. A series of novel ebselen analogues was synthesized, including hydroxy-, alkoxy- and aminomethylene derivatives, as well as hybrid species where the ebselen selenium atom is shared with other potent antioxidant structures, such as cyclic selenenyl sulfide, cyclic seleninate ester and spirodioxyselenurane moieties. Conjugates of ebselen with cholesterol, prednisolone and the radical inhibitor BHT were also prepared. The products were tested for antioxidant activity in an NMR-based assay by measuring the rate of consumption of benzyl thiol or the production of dibenzyl disulfide in the presence of hydrogen peroxide when catalyzed by the ebselen analogues. Activities ranged from 12 to 0.12 times that of ebselen. The oxidation of the 2-hydroxymethylene derivative of ebselen was faster than thiolysis in the initial step and the overall rate was further accelerated under basic conditions. The corresponding selenenyl sulfide analogue underwent very slow disproportionation under neutral conditions that was enhanced by the presence of a base catalyst. During investigation of possible fluxional behaviour of a bis-amide analogue, an unusual tetraphenyphosphonium salt of a tricoordinate selenium pincer anion was discovered with exceptionally potent catalytic activity, 130 times that of ebselen. In addition to rate measurements, X-ray crystallography and DFT computational methods were also employed to gain further structural and mechanistic insights.

Oxidation of Thiols with IBX or DMP: One-Pot Access to Thiosulfonates or 2-Iodobenzoates and Applications in Functional Group Transformations.

o-Iodoxybenzoic acid (IBX) and Dess-Martin periodinane (DMP) are employed for thiol to thiosulfonate conversion at rt. DMP is better than IBX in terms of reaction rate, conversion, and required equivalents. IBX-mediated oxidation of benzyl thiols produced thiosulfonates, whereas DMP afforded O-benzyl esters. The one-pot conversion of a thiol to an ester is unprecedented; this atom-economic transformation has potential for functional group transformations (FGTs), e.g., an alcohol and an aldehyde are accessed from benzyl thiol.

Stereoselective Synthesis of Z-Styryl Sulfides from Nucleophilic Addition of Arylacetylenes and Benzyl Thiols.

The stereoselective synthesis of Z-anti-Markovnikov styryl sulfides via an anionic thiolate-alkyne addition reaction was achieved when the terminal alkynes and benzyl mercaptans were reacted using tBuOLi (0.5 equiv) in EtOH under ambient conditions. Exclusive stereoselectivity (ca. 100%) was achieved by stereoelectronic control via anti-periplanar and anti-Markovnikov addition of benzylthiolates to phenylacetylenes. Solvolysis of lithium thiolate ion pairs in ethanol significantly suppresses the competing formation of the E-isomer. A remarkable enhancement of the Z-selectivity under a longer reaction time was observed.

A Versatile, Electrophilic Reagent for Monofluoromethylthiolation†

Comprehensive SummaryA new electrophilic monofluoromethylthiolating reagent N‐fluoromethylthiophthalimide PhthSCH2F 1 was developed. Reagent 1 could be readily synthesized from easily available starting materials benzyl mercaptan and CH2FCl in three steps. N‐Fluoromethylthiophthalimide 1 is a powerful electrophilic monofluoromethylthiolating reagent that allows the monofluoromethylthiolation of a wide range of nucleophiles including alkynes, aryl/vinyl boronic acids, electron‐rich heteroarenes, β‐ketoesters and oxindoles, as well as thiols under mild conditions.

Study of Photophysical Properties of Thiol-capped CdS Quantum Dots Doped with Gold Nanoparticles.

In this study, CdS quantum dots (QDs) capped with benzyl mercaptan (thiol) were prepared by microwave irradiation technique. The shape, size, morphology, and spectral properties of thiol-capped CdS QDs were characterized with transmission electron microscopy (TEM), scanning electron microscopy (SEM), UV-vis absorption, and photoluminescence (PL) spectrometry. The photophysical properties of synthesized thiol-capped CdS QDs in the presence of different amounts of gold nanoparticles (AuNPs) have been investigated, exhibiting strong PL quenching. The amount of fluorescence quenching was found to be dependent on the concentration of metal nanoparticles. A Stern-Volmer kinetics model was used to analyze the observed quenching mechanism as a function of the quencher (AuNPs) concentration. The Stern-Volmer plot along with the absorption spectra of thiol-capped CdS QDs in the absence and presence of AuNPs suggest the dynamic (collision) nature of quenching and rule out the possibility of static quenching. The energy transfers from QDs to Au NPs, and hence the quenching of QDs emissions provides new insight into designing novel optical-based materials and the development of FRET-based bionanosensors and phototherapeutic applications.

Asymmetric S‐Michael Reaction: Synthesis of CF2H−Containing S‐Ether Compounds through Isosteric Replacement

AbstractOptical pharmaceutical important compounds which bring CF2H to mimic the role of –SH were synthesized through the asymmetric S‐Michael addition reaction in the presence of quinine–a derived squaramide catalyst. Various sulfhydryl compounds including Benzyl mercaptan, phenthiol, alkyl thiophenol, mercaptoacetate, methyl 3‐mercaptoacrylate, and 1,4‐dithiane‐2,5‐diol were tested. The broad substrate scope, good functional group tolerance, and easy derivatization make this synthesis method very attractive.

Scalable Synthesis of the Shelf-Stable Radical Difluoromethylthiolation Reagent S-(Difluoromethyl)benzenesulfonothioate PhSO2SCF2H

A procedure for the convenient preparation of an efficient radical difluoromethylthiolation reagent, namely, S-(difluoromethyl)benzenesulfonothioate (PhSO2SCF2H), was reported. The reagent was synthesized on an approximately 500 g scale in two steps from cheap commodity sodium benzene sulfinate, benzyl mercaptan, and HCF2Cl. The key step of this protocol is to control the amount of chlorine and the reaction temperatures for the generation of key intermediate [HCF2SCl]. Differential scanning calorimetry (DSC) was carried out to demonstrate the stability of PhSO2SCF2H. Furthermore, gram-scale reaction of PhSO2SCF2H with electron-rich aromatic (hetero)hydrocarbons, alkyl carboxylic acids, and olefins was demonstrated.

Chemistry Related to the Catalytic Cycle of the Antioxidant Ebselen.

The antioxidant drug ebselen has been widely studied in both laboratories and in clinical trials. The catalytic mechanism by which it destroys hydrogen peroxide via reduction with glutathione or other thiols is complex and has been the subject of considerable debate. During reinvestigations of several key steps, we found that the seleninamide that comprises the first oxidation product of ebselen underwent facile reversible methanolysis to an unstable seleninate ester and two dimeric products. In its reaction with benzyl alcohol, the seleninamide produced a benzyl ester that reacted readily by selenoxide elimination, with formation of benzaldehyde. Oxidation of ebselen seleninic acid did not afford a selenonium seleninate salt as previously observed with benzene seleninic acid, but instead generated a mixture of the seleninic and selenonic acids. Thiolysis of ebselen with benzyl thiol was faster than oxidation by ca. an order of magnitude and produced a stable selenenyl sulfide. When glutathione was employed, the product rapidly disproportionated to glutathione disulfide and ebselen diselenide. Oxidation of the S-benzyl selenenyl sulfide, or thiolysis of the seleninamide with benzyl thiol, afforded a transient thiolseleninate that also readily underwent selenoxide elimination. The S-benzyl derivative disproportionated readily when catalyzed by the simultaneous presence of both the thiol and triethylamine. The phenylthio analogue disproportionated when exposed to ambient or UV (360 nm) light by a proposed radical mechanism. These observations provide additional insight into several reactions and intermediates related to ebselen.

ELECTRON TRANSFER REACTIONS OF BRIDGED BINUCLEAR IRON(III)- COMPLEXES: A REVIEW

Binuclear iron (III) complexes comprising of the -oxo-bridged form, [Fe2O]4+ or [Fe(OH)2]4+, and the dicarboxylic bridged chains incorporating salen or saloph ligands have been synthesized and characterized. Their close resemblance to some haeme and non-haeme iron-based enzymes has elicited a lot of interest in studying them. Biological studies have shown some of them to be good mimics of superoxide dismutase. The saloph and salen analogues also showed physiological actions very close to the porphyrins. The study of their electron transfer reactions, with a view of understanding their potential as electron transfer enzymes, has generated interesting results and some unusual kinetic behaviours. Reactions of [(FeHEDTA)2O]2+ with ascorbic acid and some thiols were second order and followed outer-sphere path mediated by ion-pairs formation. However, reaction of [Fe2(bipy)O]4+ with some reductants were zero order with respect to the oxidant and also followed outer-sphere path. Reduction of the adipato-bridged dimer, [Fe(saloph)2µ-adi], by SO32- and SO42-, S2O52-, benzyl mercaptan, mercaptobenzothiazole and thioglycolic acid followed inner-sphere paths. However, all the reactions were acid-catalysed and were mediated by intervening protonated oxidant precursor complexes.

Advanced investigation of a putative adsorption process of nine non key food odorants (non-KFOs) on the broadly tuned human olfactory receptor OR2W1: Statistical physics modeling and molecular docking study

In the present paper, statistical physics formalism was used to understand the olfactory perception via the investigation of dose-olfactory response curves of a putative adsorption process of nine non key food odorants (non-KFOs) on the broadly tuned human olfactory receptor OR2W1, in order to quantitative characterize the interactions between the nine studied non-KFOs, i. e., furfuryl sulfide, furfuryl disulfide, benzyl methyl disulfide, furfuryl methyl disulfide, benzyl methyl sulfide, 1-phenylethanethiol, benzyl mercaptan, furfuryl methyl sulfide and 3-phenylpropanol molecules and OR2W1 binding sites at a molecular level. Two advanced adsorption models have been proposed: the advanced monolayer monoenergy model (monolayer model with identical and independent olfactory receptor binding sites) (Model 1) and the advanced monolayer model with two independent types of olfactory receptor binding sites (Model 2). It was concluded that the monolayer monoenergy model was selected as the most adequate model to fit the experimental dose-olfactory response curves tabulated in literature. Actually, the numerical values of the three fitted physico-chemical parameters (RM1, n and C1) were obtained by a non-linear regression. Indeed, modeling results suggested that the number of docked non-KFOs per OR2W1 binding site n values (1.24 < n < 1.94) was always superior to 1, which indicated the non-parallel orientation of the studied odorants on the olfactory receptor and the multi-molecular adsorption mechanism. The estimated molar adsorption energy ΔEa values (ranged from 6.07 to 12.16 kJ/mol) for the nine olfactory systems confirmed the physical the exothermic characters of the adsorption process since ΔEa values were lower than 40 kJ/mol and positive. Furthermore, these estimated parameters were applied to characterize stereographically and energetically the interaction between the nine non-KFOs and OR2W1 through the determination of the human receptor binding site size distributions (RSDs) and the adsorption energy distributions (AEDs), which were spread out from 0.25 to 6.50 nm and from 0 to 22.50 kJ/mol, respectively. The docking computation between these nine non-KFOs and OR2W1 proved that the estimated binding affinities were belonged to the adsorption energies spectrum in general and the specific adsorption energy band or the molecular vibration modes limited spectrum (between 2.50 kJ/mol and 17 kJ/mol) (approximate olfactory band).

Size- and Shape-Dependent Photoexcitation Electron Transfer in Metal Nanoclusters

There are some unresolved fundamental issues for metal nanoclusters; for instance, the close-packed structure transformation from face-centered cubic (fcc) to hexagonal close-packed (hcp) has not yet been reported, and photoexcitation electron transfer is not well understood. Herein, we realized for the first time the fcc-to-hcp structure transformation and revealed the size- and shape-dependent photoexcitation electron transfer for metal nanoclusters. Specifically, a thermally induced ligand exchange method was developed, and a rod-shaped hcp Au42(SCH2Ph)32 (HSCH2Ph: benzyl mercaptan) with the largest aspect ratio was synthesized from fcc Au28(SPh-tBu)20 (HSPh-tBu: p-tert-butylphenol) and structurally resolved, which shows a sharp absorption at 815 nm and dual emission that is well interpreted by time-dependent density functional theory (TD-DFT) calculations. The structure transformation pathway was proposed, and a novel, rod-shaped hcp Au58(SR)40 with larger aspect ratio was predicted. Interestingly, it is found that the kernel-based middle-to-both ends sp ← sp photoexcitation electron transfer can be extended to other rod-like (one-dimensional) gold nanoclusters, and the major photoexcitation turns to the kernel-based sp ← sp transition from the staple-to-kernel sp ← d transition when the spherical gold nanocluster size is increased to Au42 and the Au(6sp) composition increases with increasing size for structure-similar nanoclusters. These findings deepen our understanding of metal nanocluster photoexcitation electron transfer and provide guidance for future nanocluster property tuning aimed at practical applications.

Thiol-promoted intermolecular cyclization to synthesize 1,2,4-oxadiazoles including tioxazafen under transition metal-free conditions.

A simple and efficient one-pot intermolecular annulation reaction for the synthesis of 1,2,4-oxadiazoles from amidoximes and benzyl thiols has been developed, in which benzyl thiols act as not only reactants but also organo-catalysts. The control experiments proved that thiol substrates could facilitate the dehydroaromatization step. High yield, functional group diversity and transition metal-free, extra oxidant-free, and mild conditions are the important practical features. Moreover, this protocol provides an effective alternative method for the synthesis of a commercially available broad-spectrum nematicide, tioxazafen.

Anaerobic degradation of thiobencarb by mixed culture of isolated bacteria.

Thiobencarb is a highly effective thiocarbamate herbicide frequently used in rice fields globally. In this study, three bacterial strains (Dechloromonas sp. Th1, Thauera sp. Th2, and Azoarcus sp. Th3) isolated from immobilized biomass were analyzed for thiobencarb degradation under anaerobic conditions, with nitrate serving as an electron acceptor. The experimental results showed that thiobencarb was transformed by Dechloromonas sp. Th1 and Thauera sp. Th2 to produce high concentrations of metabolites in a mineral medium. Dechloromonas sp. Th1 dechlorinated the herbicide to benzyl mercaptan, which was then degraded by Thauera sp. Th2 and Azoarcus sp. Th3. Azoarcus sp. Th3 effectively degraded intermediates, i.e. 4-chlorobenzyl alcohol, 4-chlorobenzoic acid, and benzoic acid, produced from the degradation by Dechloromonas sp. Th1 and Thauera sp. Th2. The cross-feeding, nutrient sharing, and cooperation of all isolates in the degradation process decreased the concentrations of intermediate products. The determination of the degradation kinetics showed that the utilization in the exponential phase of the mixed bacteria was consistent with the Michaelis-Menten model, with a maximum degradation rate of 1.56±0.16µM day-1. This study showed the degradation mechanisms in bacteria and the synergistic process in the degradation of thiobencarb and its metabolites.

Unexpected Formation and Potent Antioxidant Activity of Macrocyclic Dimers Containing Disulfide and Selenide Groups.

During attempts to prepare spirodithiaselenuranes as GPx mimetics, a series of unexpected dimeric macrocycles was obtained, each containing two selenide and two disulfide moieties in rings ranging from 18- to 26-membered. The products showed potent GPx-like activity in an NMR assay based on their ability to catalyze the reduction of hydrogen peroxide with benzyl thiol. The high catalytic activity was attributed to transannular effects during selenide to selenoxide oxidation. This redox process was also characterized by an induction period that indicated autocatalysis in the formation of an intermediate selenoxide from the oxidation of the corresponding selenide.

Unexpected Formation and Potent Antioxidant Activity of Macrocyclic Dimers Containing Disulfide and Selenide Groups

AbstractDuring attempts to prepare spirodithiaselenuranes as GPx mimetics, a series of unexpected dimeric macrocycles was obtained, each containing two selenide and two disulfide moieties in rings ranging from 18‐ to 26‐membered. The products showed potent GPx‐like activity in an NMR assay based on their ability to catalyze the reduction of hydrogen peroxide with benzyl thiol. The high catalytic activity was attributed to transannular effects during selenide to selenoxide oxidation. This redox process was also characterized by an induction period that indicated autocatalysis in the formation of an intermediate selenoxide from the oxidation of the corresponding selenide.

Ultrathin organic polymer with p-π conjugated structure for simultaneous photocatalytic disulfide bond generation and CO2 reduction

Combining photocatalytic organic reactions with CO2 reduction is an efficient solar energy utilization mode, but it is still limited by the organic species that can be matched and the low conversion. Herein, ultrathin organic polymer with p-π conjugated structure (TPP) was rationally designed and prepared, and showed a high yield of CO (15.2 mmol g−1) and conversion of SS coupled products (100%), far exceeding the organic polymer with PO structure. The enhanced photoredox activity of TPP is ascribed to the orbital interaction between the p-orbital on phosphorus and the π-orbitals of aromatic, which can accelerate the photoinduced charge carrier separation and improve the CO2 adsorption capacity. TPP can also be used for the dehydrocoupling of various benzyl mercaptans to the corresponding SS bond products. This work provides a new concept for the efficient synthesis of disulfide bonds combined with CO2 reduction in a photoreaction system.

Metallic Porphyrazine Networks: Synthesis, as Well as Thermal and Optical Properties for Accelerating the Oxidation of Thiols to Their Disulfides

A condensation reaction of 2,3,5,6-tetraamino-1,4-benzoquinone 1 with 4,5-Dichloro-3,6-dihydroxy-phthalonitrile 2 produced p-benzoquinone [2,3-b:2,3-b]bis[(5,8-dihydroxybenzopyrazine)-6,7-dinitrile] 3. Utilizing acetic acid with lithium/pentanol, the tetra-nitrile monomer was cyclo-tetramerized, yielding the matching network polymer, tetra p-benzoquinone[2,3-b:2,3-b]. bis[(5,8-dihydroxybenzopyrazino) porphyrazine (2H-Pz) 4a. The equivalent tetra p-benzoquinone[2,3-b:2,3-b]bis[(5,8-dihydroxybenzopyrazino) metallic porphyrazine networks (M-Pz) M = Zn 4b or Ni 4c, were obtained by cyclo-tetramerizing the tetra-nitril monomer 3 using metal salt and quinoline. The synthesized molecules’ elemental analytical results, as well as their IR and NMR spectral data, are consistent with their assigned structures. The prepared compounds have large molecular weights and metal content, indicating that reactions of tetramerization, polymerization, and chelation were all productive. The synthesized porphyrazines were proved to be excellent substrates for oxidizing thiophenol and benzyl thiol to their respective disulfides in atmospheric oxygen. The maximal production of the corresponding disulfides after 15 min was 96 percent for thiophenol and 93 percent for benzyl thiol, respectively.