Synthesis of cyclic disulfides using didecyldimethylammonium bromide as phase transfer catalyst

A convenient, practical and general method for the synthesis of symmetrical and unsymmetrical cyclic disulfides based on the reaction of sulfur with sodium sulfide in the presence of didecyldimethylammonium bromide (DDAB) as a phase transfer catalyst is described.     

Preparation of cyclic alkenylmagnesium reagents via an iodine/magnesium exchange

The reaction of various cyclic alkenyl iodides with i-PrMgCl.LiCl produces the corresponding alkenylmagnesium reagents under mild conditions. After reaction with various electrophiles, like allylic halides, disulfides, aldehydes and acid chlorides, the expected products are obtained in 53-91% yield. Remarkably, the mild conditions of the I/Mg-exchange tolerate the presence of sensitive diene functionalities.     

Ring Tension Applied to Thiol‐Mediated Cellular Uptake

The objective of the study was to explore the potential of ring tension in cyclic disulfides for thiol‐mediated cellular uptake. Fluorescent probes that cannot enter cells were equipped with cyclic disulfides of gradually increasing ring tension. As demonstrated by flow cytometry experiments, uptake into HeLa Kyoto cells increased with increasing tension. Differences in carbon‐sulfur‐sulfur‐carbon (CSSC) dihedral angles as small as 8° caused significant changes in uptake efficiency. Uptake with high ring tension was better than with inactivated or activated linear disulfides or with thiols. Conversion of thiols on the cell surface into sulfides and disulfides decreased the uptake. Reduction of exofacial disulfides into thiols increased the uptake of transporters with disulfides and inactivated controls with thiols. These results confirm the occurrence of dynamic covalent disulfide‐exchange chemistry on cell surfaces. Mechanistic and colocalization studies indicate that endocytosis does not fully account for this cellular uptake with ring tension.     

Rhodium-catalyzed organothio exchange reaction of α-organothioketones with disulfides

RhH(PPh(3))(4) and 1,2-bis(diphenylphosphino)ethane (dppe) catalyzed the organothio exchange reaction of α-organothioketones and organic disulfides. The reaction was affected by the structure of the substrate: α-phenylthio and α-alkylthio aryl ketones reacted effectively with diaryl and dialkyl disulfides; α-phenylthio dialkyl ketones reacted with diaryl disulfides but not with dialkyl disulfides; diaryl disulfides with electron-donating p-substituents were more reactive than those with electron-withdrawing p-substituents.     

Effect of ring strain on the thiolate-disulfide exchange. A computational study

B3LYP/aug-cc-pVDZ and MP2/6-31+G calculations of the reactions of HS(-) with small cyclic disulfides (dithiirane, 1,2-dithietane, 1,2-dithiolane, and 1,2-dithiane) were performed to determine the reaction mechanism. For the five- and six-membered rings, the reaction proceeds via the addition-elimination pathway, consistent with acyclic analogues. The smaller, more strained three- and four-membered rings react by the S(N)2 mechanism. Addition of the nucleophile cannot be accommodated by the small rings without concomitant ring cleavage.     

Electrochemical Oxidation of Disulfides Derived from Isocyanuric Acid

Anodic oxidation of linear and bicyclic disulfides derived from isocyanuric acid was studied by cyclic voltammetry and numerical simulation. The PM3 molecular modeling revealed three types of the highest occupied molecular orbitals determining the electrochemical reactivity of these compounds: n electrons of the sulfur atoms of the disulfide bridge in linear and N-Me- and N-Ph-substituted bicyclic disulfides, π electrons of the aromatic fragment in the disulfide with the N-2-(2-methoxyphenoxy)ethyl isocyanurate substituent, and n electrons of the sulfide sulfur atoms in the compound with the -SS- and -S- fragments in the aliphatic chain. Oxidation of the disulfides with the SS-localized highest occupied molecular orbital follows the scheme with reversible electron transfer, followed by a fast potential-determining second-order reaction and a slow current-determining first-order reaction (ECC mechanism). The isocyanurate heterocycle does not participate directly in redox transformations but stabilizes the electrochemically generated radical cations by the mechanism of transannular interaction.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 3, 2005, pp. 422–429.Original Russian Text Copyright © 2005 by Grogger, Fattakhov, Jouikov, Shulaeva, Reznik.     

REACTION OF BIS-[DIALKOXYPHOSPHORYL]- AND BIS-[DIALKOXYTHIOPHOSPHORYL]- DISULFIDES WITH TRIALKYLSILYLCYANIDES NEW ROUTE TO DIALKYLPHOSPHORO- AND DIALKYLTHIOPHOSPHORO THIOCYANIDATES AND O,O,O,O-TETRAALKYLPYROPHOS- PHOROTRITHIOATES

Abstract

The reaction of organophosphorus disulfides with trialkylsilylcyanide has been investigated. It provided direct evidence for the intermediacy of thiocyanidate >P(X)SCN, X=O, S in this type of reaction. The disulfides studied involved phosphoryl, phosphonyl and/or phosphinyl disulfides. They have been shown to follow the common mechanism. The studied reaction of thiophosphoryl disulfides with trimethylsilylcyanide represents a new and highly efficient route to tetraalkylpyrophosphoro-trithioates.     

Rhodium-catalyzed disulfide exchange reaction

A system of RhH(PPh3)4, trifluoromethanesulfonic acid, and (p-tol)3P catalyzes the disulfide exchange reaction. Treatment of two symmetrical dialkyl disulfides with the catalyst provides an equilibrium mixture of three disulfides within 15 min in refluxing acetone. The catalyst is active after reaching the equilibrium, and addition of a disulfide to the mixture changes the ratio of the products. The use of 4 mol equiv excess of one of the disulfides provides the unsymmetrical disulfide in a yield exceeding 80%. Disulfide-containing peptides also undergo an exchange reaction. The reactions of diaryl disulfides and dialkyl disulfides are even faster, and reach equilibrium within 5 min at room temperature in the presence of the rhodium complex and 1,2-bis(diphenylphosphino)ethane (dppe). This exchange reaction is considerably affected by the substituents on the disulfides. Treatment of diphenyl disulfide, di(p-tolyl) disulfide, and bis(sec-butyl) disulfide yields phenyl p-tolyl disulfide at room temperature with unchanged bis(sec-butyl) disulfide; random disproportionation occurs at reflux. The rhodium catalysis can be used for the exchange reaction of disulfides and diselenides giving selenosulfides as well as disulfides and ditellurides giving tellurinosulfides.     

Rhodium-catalyzed arylthiolation reaction of nitroalkanes, diethyl malonate, and 1,2-diphenylethanone with diaryl disulfides: control of disfavored equilibrium reaction

In the presence of catalytic amounts of RhH(PPh₃)₄ and 1,2-bis(diphenylphosphino)ethane (dppe), 1-nitroalkanes reacted with a diaryl disulfide giving 1-arylthio-1-nitroalkanes in air. The equilibrium to form thermodynamically disfavored products was shifted by the rhodium-catalyzed oxidation of thiols to disulfides and water. The thiolation reaction of cyclic nitroalkanes proceeded in high yields provided that suitable diaryl disulfides were employed depending on the substrate: di(p-chlorophenyl) disulfide was used for the thiolation reaction of 1-nitroalkanes, 1-nitrocyclopentane and 1-nitrocycloheptane with acidic α-protons (pK_a 16 and 17); di(p-methoxyphenyl) disulfide for 1-nitrocyclobutane and 1-nitrocyclohexane with less acidic α-protons (pK_a ca. 18). Related reactivities were observed in the thiolation reactions of malonate and 1,2-diphenylethanone.     

Direct preparation of nucleoside vinyl disulfides from 2-(trimethylsilyl)ethyl sulfides, an access to vinylthiols

We report here a straightforward preparation of various nucleoside vinyl disulfides in high yields under mild conditions using the new reaction of vinyl 2-(trimethylsilyl)ethyl (TMSE) sulfides with sulfenyl chlorides. This reaction allows the preparation of various mixed disulfides from stable silyl sulfides without formation of oxidizable and/or unstable thiols. The easy preparation of vinyl disulfides through this reaction should offer new perspectives in vinylthiol chemistry.     

A traceless, one-pot preparation of unsymmetric disulfides from symmetric disulfides through a repeated process involving sulfenic acid and thiosulfinate intermediates

A variable group of unsymmetric disulfides was prepared under mild reaction conditions and in high yields through the reaction of symmetric disulfides with sulfuryl chloride followed by treatment with thiols in the presence of water.     

Oxidation of disulfides with electrophilic halogenating reagents: concise methods for preparation of thiosulfonates and sulfonyl halides

The reaction of aromatic or benzylic disulfides with 2.5 equiv of Selectfluor™ in acetonitrile/water (10:1) at room temperature efficiently produced the corresponding thiosulfonates. Conversely, the reaction of disulfides with 6.5 equiv of Selectfluor™ or thiosulfonates with 4.5 equiv of Selectfluor™ in refluxing acetonitrile/water (10:1) provided sulfonyl fluorides in high yields. Accufluor™ and FP-T300™ are also effective in preparing sulfonyl fluorides from disulfides under the similar reaction conditions. Sulfonyl chlorides or sulfonyl bromides were effectively obtained from the reaction of disulfides with 6 equiv of either N-chlorosuccinimide or N-bromosuccinimide in acetonitrile/water (10:1) at room temperature. Some other electrophilic chlorinating or brominating reagents are also able to be used instead of N-chlorosuccinimide or N-bromosuccinimide for the syntheses of sulfonyl halides from disulfides. These reactions of disulfides with electrophilic halogenating reagents are convenient methods to prepare thiosulfonates and sulfonyl halides.     

Characterization of alkali induced formation of lanthionine, trisulfides, and tetrasulfides from peptide disulfides using negative ion mass spectrometry

Peptide disulfides are unstable under alkaline conditions, resulting in the formation of products containing lanthionine and polysulfide linkages. Electrospray ionization mass spectrometry has been used to characterize major species obtained when cyclic and acyclic peptide disulfides are exposed to alkaline media. Studies on a model cyclic peptide disulfide () and an acyclic peptide, oxidized glutathione, bis (^γGlu - Cys - Gly - COOH), are described. Disulfide cleavage reactions are initiated by the abstraction of C^αH or C^βH protons of Cys residues, with subsequent elimination of H₂S or H₂S₂. The buildup of reactive thiol species which act on intermediates containing dehydroalanine residues, rationalizes the formation of lanthionine and polysulfide products. In the case of the cyclic peptide disulfide, the formation of cyclic products is facilitated by the intramolecular nature of the Michael addition reaction of thiols to the dehydroalanine residue. Mass spectral evidence for the intermediate species is presented by using alkylation of thiol groups as a trapping method. Mass spectral fragmentation in the negative ion mode of the peptides derived from trisulfides and tetrasulfides results in elimination of S₂.     

Rhodium-catalyzed thiophosphinylation and phosphinylation reactions of disulfides and diselenides

Alkyl and aryl dithiophosphinates were synthesized by the reaction of disulfides with biphosphine disulfides in the presence of RhH(PPh₃)₄ and 1,2-diphenylphosphinoethane (dppe). The catalyst also promoted synthesis of thiophosphinates and selenothiophosphinates from disulfides and diselenides.     

Reduction of diaryl disulfides with 1-benzyl-1,4-dihydronicotinamide

Reduction of diaryl disulfides with 1-benzyl-1,4-dihydronicotinamide (BNAH) proceeded through a radical chain reaction, while dialkyl disulfides were found to be inert to BNAH.     

Disulfide interchange reactions by superoxide

Superoxide, which was produced by an electrochemical method, catalyzes instantaneously the interchange reaction of disulfides. The relationship between the half-wave potentials of disulfides and the amounts of superoxide required to complete the reaction were examined.     

Electrodeposition of ferrocenoyl peptide disulfides

Using electrodeposition of cyclic and acyclic Fc-peptide disulfides tightly-packed Fc-peptide monolayers were conveniently formed, which exhibit significant differences in their electron transfer kinetics.     

一锅法合成二硫醚的简便制备过程研究

双（三氯甲基）碳酸酯与三苯基膦反应生成的二氯三苯基膦在三乙胺存在下与 硫酚（醇）反应，合成了一系列收率良好的二硫醚化合物。该过程采用“一锅法” ，操作方便，后处理简单，条件温和，提供了一条合成二硫醚的重要路线。     

Synthesis of new cyclic dialkoxy disulfides

Five new cyclic dialkoxy disulfides have been synthesized and fully characterized. An X-ray structure was obtained for the 2,3-furandimethylene dialkoxy disulfide.     

Reactions of Diorganyl Disulfides with Dihaloalkanes in Basic Reductive Media. Synthesis of Bis(organylthio)alkanes

A convenient preparative synthesis of bis(organylthio)alkanes was developed. It is based on alkylation with dihaloalkanes of solutions of diorganyl disulfides in the basic reductive system hydrazine hydrate-alkali. The generation of organylthiolate anions from disulfides and the subsequent reaction of the anions with dihaloalkanes are performed in one reaction vessel without isolation of intermediate alkali metal thiolates. At the same time, the reactions of diphenyl or dithienyl disulfides with dihaloalkanes result in substitution with the thiolate anions of only one halogen atom to give the corresponding unsymmetrical sulfides. In certain cases in the presence of excess alkali the latter sulfides are dehalogenated to form alkyl vinyl sulfides.