Sulphonium Salts Research Articles

Corey‐Сhaykovsky cyclopropanation of dehydroalanine in the Ni(II) coordination environment: Electrochemical vs. chemical activation

The Corey-Chaykovsky method was used for α,α-cyclopropanation of dehydroalanine in the form of chiral Ni(II) Schiff-base complexes. For generation of the Corey ylide, electrochemical and chemical deprotonation were tested. For sulphonium salts more easily reduced than the Michael acceptor, the direct electrochemical reduction of the salt in the presence of the dehydroalanine complex gives almost quantitative yield of the cyclopropanated amino acid derivative. For the salts reduced at more cathodic potentials than the Ni-Schiff-base complex and are not prone to rearrangements, electrochemical deprotonation followed by the addition of the complex gives significantly higher yield of the cyclopropanated complex then deprotonation with common bases. Notably, insertion of the substituent either in the sulphonium salt or at the double bond of the dehydroalanine complex yields formation of the cyclopropane derivatives with the opposite configurations of the β-stereocenter. The (R;R,cis)-isomer dominates in the former case whereas the (S;R,trans)-diastereomer is formed in the latter case. To shed light on the stereoselectivity observed, the activation free energies for four alternative ring-closure steps leading to four possible diastereomers were calculated using the DFT approach.

Synthetic access to thiolane-based therapeutics and biological activity studies.

Secondary metabolites isolated from bioactive extracts of natural sources iteratively pioneer the research in drug discovery. Modern medicine is often inspired by bioactive natural products or the bio-functional motifs embedded in them. One of such consequential bio-functional motifs is the thiolane unit. Thiolane-based bioactive organic compounds have manifested a plethora of astonishing biological activities such as anti-viral, anti-cancer, anti-platelet, α-glucosidase inhibition, anti-HIV, immunosuppressive and anti-microbial activities which renders them excellent candidates in drug discovery. Hence, to scale up the accessibility of thiolane-based therapeutics its chemical syntheses is essential and in addition; a sneak peek in its biosynthesis would give a perspective for developing biomimetic syntheses. This review highlights the development of important thiolane-based therapeutics such as (i) Nuphar sesquiterpene thioalkaloids (ii) Thiosugar sulphonium salts from Salacia sp. (iii) Albomycins (iv) Thiolane-based therapeutics from Allium sp. (v) 4'-thionucleosides summarizing various synthetic strategies, biosynthesis and biological activity studies, covering literature till 2021. We anticipate that this review will inspire chemists and biochemists to take up the challenges encountered in the synthesis and development of thiolane-based therapeutics.

Photoinitiated curing of mono‐ and bifunctional epoxides by combination of active chain end and activated monomer cationic polymerization methods

AbstractPhotoinitiated cationic polymerization of mono‐ and bifunctional epoxy monomers, namely cyclohexeneoxide (CHO), 4‐epoxycyclohexylmethyl‐3′,4′‐epoxycyclohexanecarboxylate (EEC), respectively by using sulphonium salts in the presence of hydroxylbutyl vinyl ether (HBVE) was studied. The real‐time FTIR spectroscopic, gel content determination, and thermal characterization studies revealed that both hydroxyl and vinyl ether functionalities of HBVE take part in the polymerization. During the polymerization, HBVE has the ability to react via both active chain end (ACE) and activated monomer mechanisms through its hydroxyl and vinyl ether functionalities, respectively. Thus, more efficient curing was observed with the addition of HBVE into EEC‐containing formulations. It was also demonstrated that HBVE is effective in facilitating the photoinduced crosslinking of monofunctional epoxy monomer, CHO in the absence of a conventional crosslinker. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4914–4920, 2007

Efficient Clustering of Cyclic Sulphonium Salts Applying Liquid Secondary Ion Mass Spectrometry

Salt-like cluster ions of the ([cation](n)[anion](n-1))(+) type are commonly composed of mono-atomic, inorganic components. Clusters containing organic ions are also known, with nitrogen-centred cations being particularly prominent. However, sulphur-centred analogues, such as organic sulphonium salts, represent a notable exception. Fast atom bombardment and liquid secondary ion mass spectrometry of such compounds show, in general, a low tendency towards the formation of clusters. The present study reveals that sputtering of cyclic sulphonium salts leads to the efficient formation of cluster ions beyond previous observations. Cluster ions are characterised by isotopic pattern analysis and collision-induced dissociation.

UV radiation curing of epoxidized palm oil–cycloaliphatic diepoxide system induced by cationic photoinitiators for surface coatings

Epoxidized palm oil (EPO) can be cured with ultraviolet (UV) radiation using either radical, cationic or hybrid initiation. Cationic curing system has been chosen in this study due to the fact that epoxy groups present in EPO can be utilized directly to form cross links. Curing was carried out in a 20 cm wide UV IST machine. Triaryl sulphonium salts and ferrocenium salt were used as cationic photo initiators. Formulations were developed based on selected grades of EPO. Other materials employed included different types and concentrations of photo initiators, monomers and photo-sensitizer. The effect of post-cure conditions was also studied. The properties of the cured film, namely, pendulum hardness, percentage of gel content and tensile strength were determined. It was found that triarylsulphonium hexafluorophosphate exhibited low solubility in EPO. Addition of a vinyl ether monomer to the formulation did not enhance pendulum hardness and gel content of the cured films. Post-cure temperature had no significant effect on the properties of the cured film. The FTIR studies showed evidence of the ring opening of the epoxide groups present in the formulation.

Antibacterial and Bacterium Adsorbing Macromolecules

Currently studies on antibacterial macromolecules, i. e., bactericidal and bacteriostatic ones, have been made to develop a new utilization field of polymeric materials. In these studies, there are immobilizations of iodine to quaternary ammonium salts, antibiotics, antibacterial groups to macromolecular substances, as well as syntheses of polymers with quaternary ammonium salts, biguanide groups, quaternary pyridinium salts, sulphonium salts, phosphonium salts, and other antibacterial groups. On the other hand, studies have been made of bacterium adsorbing macromolecules, which can remove by adsorbing bacterial cells in water. The macromolecules are the ones based on poly(4-vinylpyridine-co-divinylbenzene), crosslinked poly(3- and 4-chloromethylated styrene-g-amine), and poly(glycidyl methacrylate-g-amine), as well as filters and microporous membranes are covered with a macromolecule based on quaternized poly(4-vinylpyridine-co-styrene). Here, a review is made of the syntheses and preparation of the respective macromolecules, as well as of their antibacterial activities and the bacterium adsorbing activities.

Antibacterial and Bacterium Adsorbing Macromolecules

Currently studies on antibacterial macromolecules, i. e., bactericidal and bacteriostatic ones, have been made to develop a new utilization field of polymeric materials. In these studies, there are immobilizations of iodine to quaternary ammonium salts, antibiotics, antibacterial groups to macromolecular substances, as well as syntheses of polymers with quaternary ammonium salts, biguanide groups, quaternary pyridinium salts, sulphonium salts, phosphonium salts, and other antibacterial groups. On the other hand, studies have been made of bacterium adsorbing macromolecules, which can remove by adsorbing bacterial cells in water. The macromolecules are the ones based on poly(4-vinylpyridine-co-divinylbenzene), crosslinked poly(3- and 4-chloromethylated styrene-g-amine), and poly(glycidyl methacrylate-g-amine), as well as filters and microporous membranes are covered with a macromolecule based on quaternized poly(4-vinylpyridine-co-styrene). Here, a review is made of the syntheses and preparation of the respective macromolecules, as well as of their antibacterial activities and the bacterium adsorbing activities.

Photopolymerization of carbazolyloxiranes with sulphonium and tropylium salts

The photopolymerization of 1-allyloxa-3-(carbazol-9-yl)-2-propanol glycidyl ether (ACPGE) and 1-(carbazol-9-yl)-4-oxa-2-pentanol glycidyl ether (COPGE) with cyclopropyldiphenylsulphonium tetrafluoroborate and tropylium hexafluorophosphate is reported. Oligomers with a degree of polymerization of 9–19 were obtained in the photopolymerization of ACPGE with these salts. The photopolymerization of COPGE yielded oligomers with a degree of polymerization of 4–5. The behaviour of tropylium and sulphonium salts is discussed. Tropylium hexafluorophosphate initiates both the photopolymerization of carbazolyloxiranes and the cationic polymerization of unsaturated monomers. Cyclopropyldiphenylsulphonium tetrafluoroborate acts exclusively as a photoinitiator.

Photopolymerization of glycidyl acrylate and glycidyl methacrylate investigated by differential photocalorimetry and FT-I.R.

The kinetics of photopolymerization of glycidyl acrylate (GA) and glycidyl methacrylate (GMA) sensitized by radical and cationic initiators have been studied using a combination of photodifferential scanning calorimetry (PDSC) and Fourier Transform i.r. spectroscopy (FT-i.r.). PDSC analysis shows that GA has much higher reactivity than GMA when a typical radical photoinitiator, 2,2-dimethoxy-2-phenylacetophenone (DMPA), was used. No great difference in rate constants and activation energies between the two monomers, except the higher conversion of GA, was found for the cationic polymerization initiated by sulphonium salts. The results of FT-i.r. show that both double bond and epoxy ring are polymerized at the same time. For both radical and cationic initiating systems, photopolymerization kinetics are also studied as a function of initiator concentration.

Investigation of liquid chromatographic systems for the separation of sulphonium salts

The liquid chromatographic separation of basic compounds encounters often many problems related to interactions between these analytes and the usual silica-based stationary phases. In this study, the difficulty of separating sulphonium salts used in the synthesis of poly(p-phenylenevinylene) is discussed. A chromatographic system using a polymer-based column for the separation of these compounds was developed that also demonstrated the high reactivity and instability of some tetrahydrothiophenium salts.

The synthesis of inhibitors for processing proteinases and their action on the Kex2 proteinase of yeast

Peptidyl chloromethane and sulphonium salts containing multiple Arg and Lys residues were synthesized as potential inhibitors of prohormone and pro-protein processing proteinases. The potencies of these compounds were assayed by measuring the kinetics of inactivation of the yeast Kex2 proteinase, the prototype of a growing family of eukaryotic precursor processing proteinases. The most potent inhibitor, Pro-Nvl-Tyr-Lys-Arg-chloromethane, was based on cleavage sites in the natural Kex2 substrate pro-alpha-factor. This inhibitor exhibited a Ki of 3.7 nM and a second-order inactivation rate constant (k2/Ki) of 1.3 x 10(7) M-1.s-1 comparable with the value of kcat./Km obtained with Kex2 for the corresponding peptidyl methylcoumarinylamide substrate. The enzyme exhibited sensitivity to the other peptidyl chloromethanes over a range of concentrations, depending on peptide sequence and alpha-amino decanoylation, but was completely resistant to peptidyl sulphonium salts. Kinetics of inactivation by these new inhibitors of a set of 'control' proteinases, including members of both the trypsin and subtilisin families, underscored the apparent specificity of the compounds most active against Kex2 proteinase.

Reaction of borane-dimethyl sulfide complex with aromatic acids: access to methyl compounds or to benzyl dimethyl sulphonium salts.

In certain conditions, the action of borane dimethyl sulfide (BMS) with aromatic carboxylic acids leads to the corresponding methyl derivatives or, in the presence of BF 3, to the benzyl dimethyl sulphonium salts.

Functionalized polymers and their applications

Part 1 Chemistry of reactive polymers - preparation and properties of functionalized polymers: preparation of functionalized polymers - polymerization, chemical functionalization of synthetic organic polymers, functionalization of biopolymers, fuvctionalization of inorganic supports properties and characterization of functionalized polymers - physical forms, solvation behaviour, porosity, permeability, stability, reactivity of functionalized polymers. Part 2 Chemical applications: polymeric reagents - polymeric phosphine reagents, polymeric sulphonium salts, polymeric halogenating reagents, polymeric condensing reagents, polymeric redox reagents, polymeric protecting groups, polymeric acylation and alkylation reagents, polymer-bound nucleophiles, miscellanous polymeric catalysts - ion exchange resin catalysts, polymeric Lewis acid and superacid catalysts, polymeric photosensitizer catalysts, polymeric hydrolyzing and decarboxylating systems, polymeric phase transfer catalysts, polymer-supported transition metal catalysts, immobilized enzymes, polymeric pH indicators, polymeric initiators separations on functionalized polymers - metal ion separations, resolution of racemic mixtures, other separations organic synthesis on polymeric carriers. Part 3 Biological applications: controlled release formulations - pharmacologically active polymers, polymeric agrochemicals and related biocides polymeric supports for active groups - polymeric food additives, polymeric sunscreen. Part 4 Other technological applications: conductive polymers polymers in energy polymers in lithographic processes polymeric nuclear track detectors polymeric liquid crystals polymeric surfactants polymeric stabilizers polymeric corrosion inhibitors polymeric flocculating agents ionomers polymers in building polymers in enhanced oil production polymers in improving fibre properties.

One-electron reduction of sulphonium salts in aqueous solution: a pulse radiolysis study

Absolute rate constants have been measured for the reduction of 1-alkylthiolanium (1a–c), 1-alkylthianium (2a–e), 1-(n-carboxyalkyl)thiolanium (3a,b) and 1–(n-carboxyalkyl)thianium (4a,b) salts, and ω-dimethylsulphonioalkanoic acids (5a,b), including biologically active S-methyl-methionine (6) and dimethyl-β-propiothetin (5b), by hydrated electrons in aqueous solutions using the pulse radiolysis method. This reaction was found to occur very rapidly (k in the range 109–1010 dm3 mol–1 s–1), the individual rate constants being dependent on the electron inductive power of the substituents on the positive sulphur centre. The sulphuranyl radical R3S˙, a possible reaction intermediate, could not be detected within the 0.1 µs time resolution of the applied technique. No reaction was observed between S-methylmethionine and CO2˙– or Me2ĊOH under experimental conditions. The one-electron reduction potential of this sulphonium salt has been estimated to be < –1.8 V. C-centred radicals produced upon the reduction of the cyclic sulphonium salts 1-methyl- and 1-ethylthiolanium and 1-methylthianium salts by e–aq were characterized by using p-benzoquinone as a radical scavenger. It was found that ring opening is the predominant process rather than the cleavage of methyl or ethyl radicals.

α-Alkylation of the Diels–Alder cycloadducts of the thioaldehyde, ethyl thioxoacetate

The cycloadduct 1a of anthracene and the labile thioaldehyde, ethyl thioxoacetate 2a, has been converted into the α-lithio derivative 1b with lithium diisopropylamide (LDA). Subsequent treatment with, separately, methyl iodide, ethyl iodide, allyl bromide and benzyl bromide gave the corresponding 12-‘alkyl’ derivatives 1c–f. Each derivative, when heated in toluene at 111 °C, dissociates to liberate anthracene and a thioketone 2, which can be trapped in situ with 2,3-dimethylbuta-1,3-diene 3 to afford the corresponding 2-substituted dihydrothiine 4 in good yield. The same set of products 4 was obtained directly by α-alkylation of the parent dihydrothiine 4a. Similarly, the 12-methyl anthracene adduct 1c gives, with cyclopentadiene and cyclohexadiene, the stereoisomeric cycloadducts 5 and 6, and 7 and 8 of the cyclic dienes and ethyl 2-thioxopropionate 2c. When treated with LDA and methyl iodide, the thioaldehyde adducts 9a and 13a of cyclopentadiene and cyclohexadiene undergo rearrangement and S-methylation, rather than C-methylation, and afford the cyclopropanecarboxylates 10a and 14a. The methyl and ethyl sulphonium salts 17a–b of the parent dihydrothiine 4a rearrange similarly to give the cyclopropanecarboxylates 19a–b. Methylation of the dilithio derivatives of the cycloadducts of thioxoacetic acid has also been investigated. The cyclopropanecarboxylic acid 14b was found to rearrange slowly in the crystalline state to give the epimeric γ-lactones 15 and 16.

Photolysis of tris(4-tert-butoxycarbonyloxyphenyl) sulphonium salts. A mechanistic study

Tris(4-tert-butoxycarbonyloxyphenyl)sulphonium salts of the structure Ar3S+X–(X–: CF3SO3– or AsF6–) were irradiated with UV light in acetonitrile or dimethyl sulphoxide solution. Product analysis by ion pair chromatography (IPC), 1H NMR measurements and IR spectroscopy revealed that simultaneously bis(4-tert-butoxycarbonyloxyphenyl) sulphide, Ar2S, and a protonic acid (CF3SO3H or HAsF6) were formed. The latter catalyses the decomposition of the tert-butylcarbonate groups in the absence of water at room temperature. In the presence of water the acids dissociate, and H3O+ ions, thus formed, only catalyse the decomposition significantly at elevated temperatures (T > 70 °C). Therefore, photolysis products formed in the absence of water consist, apart from (4-HO–C6H4)2S, essentially of a mixture of salts of the ions: Ar2(4-HO–C6H4)S+, Ar(4-HO–C6H4)2S+ and (4-HO–C6H4)3S+. In addition to these products, (ButOCO2-C6H4)2S and an as yet unidentified product were formed when the irradiation was performed in the presence of water. Quantum yields (in the absence of water) determined by IPC are: φ[–salt]= 0.2 and φ[(4-HO–C6H4)2S]= 0.1.

A new method for radical generation: reductive C–Se or C–S bond cleavage of cyclic onium salts

2-Methyl-3,4-dihydro-1 H-2-benzoselenopyranium salt (1) was reduced by some metallic reagents or magnesium metal via the single-electron transfer (SET) process to give 2-[2-(methylseleno)ethyl]-toluene (2). Magnesium metal was a good SET reducing agent. Some other selenonium or sulphonium salts (7), (14). (22), (27) and (32) were similarly reduced by magnesium. Particularly, sonication accelerated the reductions. Iµ-Eneselenonium salt (43) was treated with activated magnesium to give a cyclised pyrrolidine derivative (44).

S-alkylation of α-thioether iron compounds by [Ph3C]+and [Fe(η-C5Me5)(CO)2(CH2)]+

Treatment of the thiomethyl complexes [Fe(η-C5Me5)(CO)2(CH2SR)](R = Me or Ph) with [Ph3C]+ or [Fe(η-C5Me5)(CO)2(CH2)]+ results in S-alkylation, affording the sulphonium salts [Fe(η-C5Me5)(CO)2{CH2S(R)CPh3}]+ and [{Fe(η-C5Me5)(CO)2CH2}2SR}]+ respectively; the former show promise as agents for methylene transfer to alkenes.

MECHANISTIC ASPECTS OF CYCLIC SULPHONIUM SALT FORMATION AND HYDROLYSIS OF 1,n-HALO(ALKYLTHIO) ALKANES

Abstract Cyclization rate constants for various 1,n-halo(alkylthio)alkanes X[sbnd](CH2) n [sbnd]S[sbnd]R with n=4 and n=5 were determined in CH3CN, CH2CI2, C6H14, CDCI3 and H2O/CH3CN (9:1) at T=25°C. The rate of formation of the five- and six-membered cyclic sulphonium salts depends on the halogen atom (I>Br>Cl), the number of methylene groups between sulphur and halogen (n=4>n=5), on the alkyl group R and on the solvent. In aqueous CH3CN hydrolysis becomes competetive. The hydrolysis rate constants of several 1,n-halo(alkylthio)alkanes with n>3 were determined in water at T=25 and 60°C and compared to those of some alkyl halides and the mustard derivative 1-chloro-2-methylthioethane. Hydrolysis of the chloro compounds is slower than of the bromo and iodo analogoues and depends on the number of methylene groups (n) between halogen and sulphur.

Synthesis of lysine-containing sulphonium salts and their properties as proteinase inhibitors.

Some sulphonium salts derived from lysine were synthesized with the general structure R-Lys-CH2S+-(alkyl)2. They were examined as inhibitors of the cysteine proteinase clostripain, which has a preference for cleaving peptide bonds at the carboxy group of basic amino acids, and of a number of trypsin-related serine proteinases. Clostripain was irreversibly inactivated by all reagents examined, but in the case of the serine proteinases, depending on the reagent structure, irreversible and reversible inhibitions were observed. These were kinetically characterized.