Dialkyl Disulfides Research Articles

Alkylthiolation of Aryl Halides under Electrochemical Conditions.

An electrochemical protocol for the alkylthiolation of aryl halides was developed. By using dialkyl disulfides as the alkylthio sources, Mg plate as the sacrificial anode and graphite felt (GF) as the cathode, a series of aryl sulfides were obtained in moderate to good yields. The approach was also suitable for the synthesis of aryl selenides. This method has the features such as simple reaction conditions and good functional group compatibility, which makes it have a good application prospect in organic synthesis and drug synthesis.

Reprocessable Polymer Networks Containing Sulfur-Based, Percolated Dynamic Covalent Cross-Links and Percolated or Non-Percolated, Static Cross-Links.

One method to improve the properties of covalent adaptable networks (CANs) is to reinforce them with a fraction of permanent cross-links without sacrificing their (re)processability. Here, a simple method to synthesize poly(n-hexyl methacrylate) (PHMA) and poly(n-lauryl methacrylate) (PLMA) networks containing static dialkyl disulfide cross-links (utilizing bis(2-methacryloyl)oxyethyl disulfide, or DSDMA, as a permanent cross-linker) and dynamic dialkylamino sulfur-sulfur cross-links (utilizing BiTEMPS methacrylate as a dissociative dynamic covalent cross-linker) is presented. The robustness and (re)processability of the CANs are demonstrated, including the full recovery of cross-link density after recycling. The authors also investigate the effect of static cross-link content on the stress relaxation responses of the CANs with and without percolated, static cross-links. As PHMA and PLMA have very different activation energies of their respective cooperative segmental mobilities, it is shown that the dissociative CANs without percolated, static cross-links have activation energies of stress relaxation that are dominated by the dissociation of BiTEMPS methacrylate cross-links rather than by the cooperative relaxations of backbone segments, i.e., the alpha relaxation. In CANs with percolated, static cross-links, the segmental relaxation of side chains, i.e., the beta relaxation, is critical in allowing for large-scale stress relaxation and governs their activation energies of stress relaxation.

Nickel‐Catalyzed Synthesis of Thioesters from Amides and Disulfides

AbstractA novel nickel‐catalyzed practical and simple synthesis of thioesters from amides and disulfides has been developed. Diverse substituted aromatic amides are capable of coupling with diaryl or dialkyl disulfides via C−N/S−S bonds cleavage to produce the desirable thioesters in moderate to good yields. This procedure features cheap metals, novel and easily preparative substrates, providing a simple and practical access to a variety of thioesters without toxic thiols or CO gas.

Visible-Light-Mediated Annulation/Thiolation of 2-Isocyanobiaryls with Disulfides to Organoylthiophenanthridines Derivatives.

A visible-light-induced annulation/thiolation of 2-isocyanobiaryls with dialkyl(aryl)disulfides has been established, delivering a sustainable and atom-economic route to 6-organoylthiophenanthridines with wild functional group tolerance and good to excellent yields under oxidant-, base-, and transition-metal-free conditions.

Synthesis of Tetrathiophosphates from White Phosphorus

Comprehensive SummaryA transition‐metal‐free one‐pot direct synthesis of tetrathiophosphates (R1S)2P(S)SR2 from white phosphorus (P4), through intermediate sodium alkyltetrathiophosphates (R1S)2P(S)SNa, is presented. In the presence of NaSH, various disulfides such as diaryl disulfidbges and dialkyl disulfides are easily coupled with P4 to give sodium alkyltetrathiophosphates (R1S)2P(S)SNa in almost quantitative yield, which react with alkyl halides in one pot to generate (R1S)2P(S)SR2. Furthermore, S‐(2‐cyanoethyl)‐substituted tetrathiophosphates (R1S)2P(S)SCH2CH2CN are successfully designed as a kind of tetrathiophosphorylation reagent to react with diaryl iodonium salts involving deprotection‐dealkylation process.

Synthesis of Dithioacetals through Iodine-Promoted Insertion Reactions of Vinylsilane to Disulfides and its Application to Diselenoacetalization

AbstractDescribed herein is an iodide-promoted insertion reaction of vinyltrimethylsilane into diaryl or dialkyl disulfides in the presence of iodine/KF leading to the production of a 1,1′-adduct, a dithioacetal derivative. This method also accomplishes insertion into a diaryl diselenide to afford the corresponding diselenoacetal derivative.

Tagging Peptides with a Redox Responsive Fluorescent Probe Enabled by Photoredox Difunctionalization of Phenylacetylenes with Sulfinates and Disulfides.

Herein, we describe a photoredox three-component atom-transfer radical addition (ATRA) reaction of aryl alkynes directly with dialkyl disulfides and alkylsulfinates, circumventing the utilization of chemically unstable and synthetically challenging S-alkyl alkylthiosulfonates as viable addition partners. A vast array of (E)-β-alkylsulfonylvinyl alkylsulfides was prepared with great regio- and stereoselectivity. Moreover, this powerful tactic could be employed to tag cysteine residues of complex polypeptides in solution or on resin merging with solid phase peptide synthesis (SPPS) techniques. A sulfonyl-derived redox responsive fluorescent probe could be conveniently introduced on the peptide, which displays green fluorescence in cells while showing blue fluorescence in medium. The photophysical investigations reveal that the red shift of the emission fluorescence is attested to reduction of carbonyl group to the corresponding hydroxyl moiety. Interestingly, the fluorescence change of tagged peptide could be reverted in cells by treatment of H2O2, arising from the reoxidation of hydroxyl group back to ketone by the elevated level of reactive oxygen species (ROS).

Nickel‐Catalyzed Thiocarbonylation of Aryl Iodides with Dialkyl Disulfides for the Synthesis of Thioesters

AbstractA nickel‐catalyzed molybdenum‐promoted carbonylative synthesis of thioesters between aryl iodides and dialkyl disulfides has been developed. This method provides a novel and practical route to aryl thioesters under CO‐gas‐free conditions. Using Mo(CO)6 as a solid CO source, many thioesters were obtained in moderate yields without expensive metals such as palladium.

Decatungstate-catalyzed radical disulfuration through direct C-H functionalization for the preparation of unsymmetrical disulfides

Unsymmetrical disulfides are widely found in the areas of food chemistry, pharmaceutical industry, chemical biology and polymer science. Due the importance of such disulfides in various fields, general methods for the nondirected intermolecular disulfuration of C-H bonds are highly desirable. In this work, the conversion of aliphatic C(sp3)-H bonds and aldehydic C(sp2)-H bonds into the corresponding C-SS bonds with tetrasulfides (RSSSSR) as radical disulfuration reagents is reported. The decatungstate anion ([W10O32]4−) as photocatalyst is used for C-radical generation via intermolecular hydrogen atom transfer in combination with cheap sodium persulfate (Na2S2O8) as oxidant. Herein a series of valuable acyl alkyl disulfides, important precursors for the generation of RSS-anions, and unsymmetrical dialkyl disulfides are synthesized using this direct approach. To demonstrate the potential of the method for late-stage functionalization, approved drugs and natural products were successfully C-H functionalized.

Experimental substantiation of the tentatively safe level of diethyl disulfide in the air of the working area and the atmospheric air of populated areas

Introduction. Diethyl disulfide belongs to the group of dialkyl disulfides, is a part of disulfide oil and a mixture of dialkyl disulfides. As a result of industrial purification of hydrocarbon raw materials from mercaptans, tens of thousands of tons of dialkyldisulfides and their mixtures are accumulated annually, the toxicity and danger of which have not been fully studied. No hygiene standards have been developed for diethyl disulfide. Materials and methods. Studies of the effects of diethyl disulfide were carried out in non-linear animals (rats and mice). The toxic properties of diethyl disulfide were studied under the conditions of single and repeated exposure to the intragastric, intraperitoneal, inhalation and cutaneous routes of entry into the body. Results. Based on the studies carried out, the toxicometric parameters of diethyl disulfide were established. Average lethal dose with intragastric administration LD50 = 1575 mg/kg, average lethal concentration CL50 = 18700 mg/m3, coefficient of possible inhalation poisoning CPIP = 1.3, limit of acute inhalation action (Limac) is set at 120 mg/m3, acute zone Zac = 156, cumulation coefficient was 3.2. Diethyl disulfide does not have a skin-resorptive toxic effect, but it has a moderately pronounced irritating effect on the mucous membrane of the eyes. Limitations of the study. The results of the diethyl disulfide exposure assessment are given for two animal species and four main routes of entry. Conclusion. The data obtained indicate that diethyl disulfide is a moderately hazardous substance with a single intragastric, inhalation and cutaneous route of entry into the body. The cumulative properties of diethyl disulfide are moderately expressed. Based on the analysis of literature data, the results of experimental studies and mathematical forecasting, a value of 4.0 mg/m3 is recommended as an approximate safe level of exposure in the air of the working area, in the atmospheric air of urban and rural settlements - 0.04 mg/m3.

Salivary biochemical assessments to determine smoking cessation under smoking cessation program

The study aim was to investigate the potential of salivary biochemical assessments to determine smoking cessation in patients under smoking cessation programs. The study validated smoking behavior and degree of nicotine dependence using Fagerström test for nicotine dependence in smokers and non-smokers. Protein components were examined using Raman spectroscopy. Salivary matrix metalloproteinases-8 (MMP-8) levels were analyzed using Quantikine human total MMP-8 immunoassay-kits. Thiocyanate (SCN−) concentrations, peroxidase and glutathione-peroxidase activities were determined using spectrophotometric methods. Human mononuclear cell line was examined for M1 polarization. The data were analyzed using Fisher’s exact test and two-tailed paired t-test at α = 0.05. Amide I peak in smoker group was significantly reduced as compared to non-smokers (p < 0.05). Sulfhydryl bond, dialkyl disulfides SS-stretch and corresponding disulphide bond at 500−545 cm-1 were significantly increased in smokers (p < 0.05). The CH2 wag showed higher intensity amongst smoker group representing a recoil of carbon atoms. Salivary MMP-8 levels of participants after smoking cessation was significantly lower than smoking salivary levels (p < 0.05). The SCN− and peroxidase concentrations were significantly higher in smoking group whereas an M1 polarization was seen in non-smokers. Salivary biochemical analysis can aid clinicians to verify smoking cessation in patients under smoking cessation programs.

Time‐of‐flight secondary ion mass spectrometry and gas chromatography–mass spectrometry studies of alkanethiol self‐assembled monolayers on nanoporous gold surfaces

The dimerization of alkanethiol mixtures (hexanethiol, octanethiol, and dodecanethiol) to form self‐assembled monolayers (SAMs) from headspace on nanoporous gold surfaces was studied for the first time using gas chromatography (GC/MS) and time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS). The nanoporous gold surfaces were obtained by an acidic etching of a 585‐gold alloy. Field emission scanning electron microscopy (FE‐SEM) was utilized to study the change of the surface geometry and porosity of the gold surfaces before and after etching. Alkanethiols were deposited from the vapor phase above the thiol solutions (headspace) on nanoporous gold plates and nanoporous gold solid‐phase vmicroextraction (SPME) fibers. The nanoporous gold substrates were analyzed by TOF‐SIMS and GC/MS, respectively. The TOF‐SIMS spectra exhibited various gold–sulfur ion clusters and specific peaks related to the adsorption of thiols such as deprotonated monomers, thiolate–Au, dimers (e.g., dialkyl sulfides–Au and dialkyl disulfides–Au). The GC/MS analysis of headspace extractions of alkanethiol mixtures by nanoporous gold SPME fibers showed a high extraction efficiency of alkanethiol, dialkyl sulfide, and dialkyl disulfide when compared with the commercial SPME fibers (DVB‐CAR‐PDMS and CAR‐PDMS). Different GC/MS optimization factors were studied including the extraction time and desorption temperature.

Cross-Dehydrogenative Coupling of Azoarenes with Dialkyl Disulfides.

A catalyst-free cross-dehydrogenative coupling reaction of purines and some azoarenes with dialkyl disulfides has been developed. This procedure provided a novel strategy to construct unsymmetrical disulfides through the α-heterocyclic functionalization of symmetrical dialkyl disulfides. The S-S bond was successfully tolerated in this transformation. The mild conditions and the broad scope of azoarenes indicated the potential application of this procedure.

One‐Pot Synthesis of Dithioacetals and Diselenoacetals: An Indium‐Catalyzed Reductive Insertion into Disulfides and Diselenides with Orthoesters as a Methylene Source

AbstractHerein it is described that an indium(III) compound effectively catalyzes a reductive insertion into either diaryl or dialkyl disulfides with orthoesters to produce a variety of dithioacetal derivatives. This method could also be adapted to the diselenoacetalization of diselenides. During a series of reductive insertions using this method, it is noteworthy that an orthoester functions as a masked methylene moiety.

Synthesis of 4-Sulfenyl Isoxazoles through AlCl3-Mediated Electrophilic Cyclization and Sulfenylation of 2-Alkyn-1-one O-Methyloximes.

An efficient method for the synthesis of 4-sulfenyl isoxazoles has been developed via AlCl3-mediated electrophilic cyclization/sulfenylation of 2-alkyn-1-one O-methyloximes. Remarkably, N-arylsulfanylsuccinimides are employed as electrophiles for the construction of 4-arylsulfanyl isoxazoles, and 4-alkylsulfanyl isoxazoles are accessed with dialkyl disulfides as electrophiles.

Selenosilane-Promoted Selective Mild Transformation of N-Thiophthalimides into Symmetric Disulfides

The reactivity of N-thiophthalimides with silyl chalcogenides is described. Treatment of N-thiophthalimides with bis(trimethylsilyl) sulfide [(Me3Si)2S] leads to the formation of a mixture of the corresponding disulfides and trisulfides. On the other hand, N-thiophthalimides react with bis(trimethylsilyl) selenide [(Me3Si)2Se] under TBAF catalysis to smoothly give variously substituted diaryl, divinyl, and dialkyl disulfides; formation of a selenotrisulfide (dithiaselane, RSSeSR) is rationalized as an intermediate. Exploiting the different chemical behavior of silyl chalcogenides, we have disclosed a novel, selective, and operationally simple method to access disulfides in good yields under mild conditions.

Environmentally friendly synthesis of unsymmetrical dialkyl disulfides by reacting organic halides with thiourea and sodium thiosulfate in an aqueous medium

The developed synthetic procedure is economical and environmentally friendly. It also avoids using toxic organic solvents, and an oxidant or a reductant.

Catalytic Conversion of Petroleum Dialkyl Disulfides to Dialkyl Sulfides

A mixture of lower dialkyl disulfides (R = C1–C2) obtained by the demercaptanization of petrochemicals is converted to alkanethiols and dialkyl sulfides under the action of solid acid catalysts. In a helium medium, the main reaction products are methanethiol and ethanethiol; the total dialkyl sulfide selectivity is less than 20%. In a mixture of disulfides with methanol, the main reaction products are dimethyl, methyl ethyl, and diethyl sulfides; the total selectivity for these products achieves 98%.

Thermal conversion of primary alcohols to disulfides via xanthate intermediates: an extension to the Chugaev elimination.

Primary alcohols are converted into dialkyl disulfides via heating in situ generated O-alkyl S-difluoro(ethoxycarbonyl)methyl xanthates from ethyl bromodifluoroacetate and potassium xanthates, prepared from primary alcohols and carbon disulfide in the presence of KOH. The reaction mechanism is suggested as an alkyl C[1,3] shift followed by a radical mechanism. This extends to the Chugaev elimination which yields olefins. The current research provides easy access to dialkyl disulfides from commercially available primary alkanols.

Speciation of CuCl and CuCl2 Thiol-Amine Solutions and Characterization of Resulting Films: Implications for Semiconductor Device Fabrication.

Thiol-amine mixtures are an attractive medium for the solution processing of semiconducting thin films because of their remarkable ability to dissolve a variety of metals, metal chalcogenides, metal salts, and chalcogens. However, very little is known about their dissolution chemistry. Electrospray ionization high-resolution tandem mass spectrometry and X-ray absorption spectroscopy were employed to identify the species formed upon dissolution of CuCl and CuCl2 in 1-propanethiol and n-butylamine. Copper was found to be present exclusively in the 1+ oxidation state for both solutions. The copper complexes detected include copper chlorides, copper thiolates, and copper thiolate chlorides. No complexes of copper with amines were observed. Additionally, alkylammonium ions and alkylammonium chloride adducts were observed. These findings suggest that the dissolution is initiated by proton transfer from the thiol to the amine, followed by coordination of the thiolate anions with copper cations. Interestingly, the mass and X-ray absorption spectra of the solutions of CuCl and CuCl2 in thiol-amine were essentially identical. However, dialkyl disulfides were identified by Raman spectroscopy as an oxidation product only for the copper(II) solution, wherein copper(II) had been reduced to copper(I). Analysis of several thiol-amine pairs suggested that the dissolution mechanism is quite general. Finally, analysis of thin films prepared from these solutions revealed persistent chlorine impurities, in agreement with previous studies. These impurities are explained by the mass spectrometric finding that chloride ligands are not completely displaced by thiolates upon dissolution. These results suggest that precursors other than chlorides will likely be preferred for the generation of high-efficiency copper chalcogenide films, despite the reasonable efficiencies that have been obtained for films generated from chloride precursors in the past.