Regioselectivity of the reaction of 4H-1,2,4-triazole-3-thiol derivatives with chloroethynylphosphonates and structure of the products

Chloroethynylphosphonates reacted with 4H-1,2,4-triazole-3-thiols in anhydrous acetonitrile to afford fused heterocyclic compounds, 6-(dialkoxyphosphoryl)-3H-thiazolo[3,2-b][1,2,4]triazol-7-ium chlorides, with high regioselectivity. The products were converted into inner salts (zwitterions) of the corresponding phosphonic acids or their monoesters with the positive charge localized on N⁷. A probable reaction mechanism implies initial formation of sulfonium ion via attack by the thionic sulfur atom on the acetylenic carbon atom linked to chlorine, followed by intramolecular cyclization involving attack on the other acetylenic carbon atom by N² of the triazole ring.     

Stereochemistry of α,α′-difluorosuccinic acids

Treatment of both dimethyl (?)-D-tartrate (IVa) and dimethyl (+)-L- tartrate (Va) with sulfur tetrafluoride gave dimethyl meso-α,α′-difluorosuccinate (Ia). The same reagent converted dimethyl meso-tartrate (IlIa) to a racemic mixture of dimethyl D- and L-α,α′-difluorosuccinate (IIa). This outcome resulting from the replacement of hydroxyl by fluorine with inversion of configuration at one and retention of configuration at the other chiral carbon atom can be rationalized by assuming the formation of a cyclic intermediate. This is opened by a subsequent S_N2 reaction with fluoride ion followed by a four-center displacement of sulfuroxy group by fluorine. The respective configurations of the dimethyl α,α′-difluorosuccinates Ia and IIa were established by ¹H and ¹⁹F NMR using an optically active chemical shift reagent and confirmed by converting the esters to the corresponding acids and these in turn to the cis- and trans-α,α′-difluorosuccinic anhydrides, respectively.     

Experimental and theoretical study of the gas-phase interaction between ionized nitrile sulfides and pyridine

The gas-phase reactivity of ionized nitrile sulfides, R-C≡N⁺-S^·, towards neutral pyridine was studied both experimentally (six sector hybrid mass spectrometer) and theoretically (density functional theory and Møller-Plesset ab initio calculations). An ionized sulfur atom transfer and a cycloaddition process respectively yielding ionized pyridine N-thioxide and a thiazolopyridinium cation were observed. Whereas the very efficient S^·+ transfer reaction probably involves the intermediacy of several ion-molecule complexes, the thiazolopyridinium ion formation is likely to be initiated by an electrophilic attack of the R-C≡N⁺-S^· ion on the nitrogen atom of pyridine; the resulting intermediate then undergo an intramolecular substitution of an α-hydrogen atom by the sulfur atom.     

Quantum Chemical Study of Mechanisms of Organic Reactions: VII. Reaction of Ethane-1,2-dithiol with 1,3-Dichloropropene in the System Hydrazine Hydrate–KOH

A mechanism has been proposed for the reaction of 1,3-dichloropropene with ethane-1,2-dithiol in the system hydrazine hydrate–potassium hydroxide on the basis of DFT quantum chemical calculations [B3LYP/6-311++G(d,p)]. The proposed mechanism involves several consecutive steps, in particular nucleophilic substitution of chlorine at the sp³-hybridized carbon atom by sulfur, prototropic allylic rearrangement of the monosubstitution product with double bond migration toward the sulfur atom, dithiolane ring closure via nucleophilic attack of the second thiolate group on the carbon atom in the γ-position with respect to the second chlorine atom, and prototropic allylic rearrangement of 2-vinyl-1,3-dithiolane to more stable 2-ethylidene-1,3-dithiolane.     

Flash photolysis study for reactions of NO3· with sulfur compounds in acetonitrile solution

The rate constants for the reaction of NO₃· with sulfur compounds in acetonitrile have been determined by the flash photolysis method. The rate constant for dimethyl sulfone (2.7 × 10⁴ M^?1s^?1 at ?10°C) is larger than that of the deuterium derivative, indicating that NO₃· abstracts the hydrogen atom from dimethyl sulfone. In the case of dimethyl sulfide, the rate constant was evaluated to be 1.5 × 10⁹ M^?1 s^?1 at ?10°C; the transient absorption band attributable to the cation radical was observed after the decay of NO₃·, suggesting the electron transfer reaction from the sulfide to NO₃·. For diphenyl sulfide and dimethyl disulfide, the electron transfer reactions were also confirmed. For dimethyl sulfoxide, the reaction rate constant of 1.2 × 10⁹ M^?1 s^?1 (at ?10°C) was not practically affected by the deuterium substitution, suggesting that NO₃· adds to sulfur atom forming (CH₃)₂?(O)-ONO₂. On the other hand, for diphenyl sulfoxide, the electron transfer reaction occurs. By the comparison of these rate constants in acetonitrile solution with the reported rate constants in the gas phase, the change of the reaction paths was revealed.     

The effect of the sixth sulfur ligand in the catalytic mechanism of periplasmic nitrate reductase

The catalytic mechanism of nitrate reduction by periplasmic nitrate reductases has been investigated using theoretical and computational means. We have found that the nitrate molecule binds to the active site with the Mo ion in the +6 oxidation state. Electron transfer to the active site occurs only in the proton‐electron transfer stage, where the Mo^V species plays an important role in catalysis. The presence of the sulfur atom in the molybdenum coordination sphere creates a pseudo‐dithiolene ligand that protects it from any direct attack from the solvent. Upon the nitrate binding there is a conformational rearrangement of this ring that allows the direct contact of the nitrate with Mo^VI ion. This rearrangement is stabilized by the conserved methionines Met141 and Met308. The reduction of nitrate into nitrite occurs in the second step of the mechanism where the two dimethyl‐dithiolene ligands have a key role in spreading the excess of negative charge near the Mo atom to make it available for the chemical reaction. The reaction involves the oxidation of the sulfur atoms and not of the molybdenum as previously suggested. The mechanism involves a molybdenum and sulfur‐based redox chemistry instead of the currently accepted redox chemistry based only on the Mo ion. The second part of the mechanism involves two protonation steps that are promoted by the presence of Mo^V species. Mo^VI intermediates might also be present in this stage depending on the availability of protons and electrons. Once the water molecule is generated only the Mo^VI species allow water molecule dissociation, and, the concomitant enzymatic turnover. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

Treatment of dimethyl (+)-L-tartrate with sulfur tetrafluoride

Treatment of dimethyl (+)-L-tartrate (I) with sulfur tetrafluoride results in the formation of an intermediate, 2-fluoro-1,2-bis(methoxycarbonyl)ethyl fluorosulfite (II), which under the action of hydrogen fluoride, present in the reaction mixture, is converted into dimethyl (?)(2S:3S)-2-fluoro-3-hydroxysuccinate (III). The reaction of the latter with SF₄ leads to dimethyl meso-2,3-difluorosuccinate (IV). The structure and configurations of the compounds obtained were established by ¹H and ¹⁹F NMR. Treatment of dimethyl (+)-L-tartrate (I) with sulfur tetrafluoride in the presence of excessive hydrogen fluoride gave dimethyl meso-2,3-difluorosuccinate in 96% yield.     

New synthesis of 2-amino-3-cyano-4,5-tetramethylenethiophene

We have shown that 2-amino-3-cyano-4,5-tetramethylenethiophene (IV) is formed in the reaction of cyclohexanethione (I) with malononitrile (II) and sulfur in the presence of triethylamine. The reaction proceeds through a step involving the formation of cyclohexylidenemalononitrile (III) and occurs via attack by the malononitrile anion on the sulfur atom of the thiocarbonyl group of I. Δ^2,α-Bornanylmalononitrile (V) was similarly obtained from thiocamphor and II; the latter reaction cannot be realized with camphor because of the steric hindrance of the carbonyl carbon atom.     

Origin of enantioselectivity with heterobidentate sulfide-tertiary amine (sp) ligands in palladium-catalyzed allylic substitution

A series of new chiral heterobidentate sulfide-tertiary amine (sp³) ligands 3a-c, 6 were readily prepared from cheap and easily available (R)-cysteine and l-(+)-methionine. A Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate was used as a model reaction to examine the catalytic efficiencies of these aziridine sulfide ligands, and ligand 3b afforded the enantioselectivity of up to 91% ee. The origin of enantioselectivity for heterobidentate sulfide-tertiary amine (sp³) ligands was first rationalized based on X-ray crystallographic data, and NMR spectroscopic data for relevant intermediate palladium allylic complexes. Our results demonstrated that the sulfur atom was a better π-allyl acceptor than the nitrogen atom for heterobidentate sulfide-tertiary amine (sp³) ligands, and the steric as well electronic properties of the palladium allylic complexes were crucial for the enantioselectivity.     

Molecular diversity of triphenylphosphine promoted reaction of electron-deficient alkynes and arylidene Meldrum acid (N,N'-dimethylbarbituric acid)

The three-component reaction of triphenylphosphine, dimethyl hex-2-en-4-ynedioate and arylidene N,N'-dimethylbarbituric acids in dry methylene dichloride at room temperature afforded trans-1,3-disubstituted 7,9-diazaspiro[4.5]dec-1-enes in good yields and with high diastereoselectivity. However, the similar three-component reaction with arylidene Meldrum acids resulted in a mixtures of cis/trans-1,2-disubstituted 7,9-dioxaspiro[4.5]dec-1-enes. Additionally, the three-component reaction of triphenylphosphine, dimethyl but-2-ynedioate and arylidene Meldrum acids gave polysubstituted 5-(triphenyl-λ⁵-phosphanylidene)cyclopenta-1,3-dienes. A plausible reaction mechanism was proposed for the formation of various products with different regioselectivity and diastereoselectivity.     

S‐Trifluoromethylation of Thiols by Hypervalent Iodine Reagents: A Joint Experimental and Computational Study

The radical trifluoromethylation of thiophenol in condensed phase applying reagent 1 (3,3‐dimethyl‐1‐(trifluoromethyl)‐1λ³,2‐benziodoxol) has been examined by both theoretical and experimental methodologies. On the basis of ab initio molecular dynamics and metadynamics we show that radical reaction mechanisms favourably compete with polar ones involving the S‐centred nucleophile thiophenol, their free energies of activation, ΔF^≠, lying between 9 and 15 kcal mol^?1. We further show that the origin of the proton activating the reagent is important. Hammett plot analysis reveals intramolecular protonation of 1 , thus generating negative charge on the sulfur atom in the rate‐determining step. The formation of a CF₃ radical can be thermally induced by internal dissociative electron transfer, its activation energy, ΔF^≠, amounting to as little as 10.8 and 2.8 kcal mol^?1 for reagent 1 and its protonated form 2 , respectively. The reduction of the iodine atom by thiophenol occurs either subsequently or in a concerted fashion.     

Flash photolysis resonance fluorescence investigation of the reaction of OH radicals with dimethyl sulfide

Rate constants for the reaction of OH radicals in a homogeneous gas phase reaction with dimethyl sulfide have been determined using the flash photolysis resonance fluorescence technique over the temperature range 273–400 K. The data (combined with the results of another recent study) can be fit to the Arrhenius expression k = (6.08 ± 2.54) × 10^?12 exp[(134 ± 135)/T] cm³ molecule^?1 s^?1 applicable from 273–426 K. The results are discussed in terms of reaction mechanisms and in light of recent suggestions that dimethyl sulfide plays an important role in the transport of natural sulfur to the earth's atmosphere.     

A SERS spectroelectrochemical investigation of the interaction of O-isopropyl-N-ethylthionocarbamate with copper surfaces

The interaction of the sulfide mineral flotation collector, O-isopropyl-N-ethylthionocarbamate (IPETC), with copper surfaces has been investigated by surface enhanced Raman scattering (SERS) spectroscopy. Adsorption of IPETC has been shown to involve a charge transfer process in which the sulfur atom in the organic species becomes bonded to a copper atom in the metal surface and the hydrogen is displaced from the nitrogen atom to form a hydrogen ion in solution. IPETC and copper IPETC compounds were characterised by ¹³C NMR and Raman spectroscopy to provide a basis for identifying surface species. The formal potential for the Cu ∣ IPETC system in acid and neutral solutions was found to be 0.131 V and the dependence of the reversible potential on IPETC concentration and on pH to be in agreement with the proposed mechanism. The SERS investigations showed that adsorption of IPETC commenced at a potential more than 0.31 V below the reversible value for the formation of the bulk copper compound; this behaviour is analogous to that previously found for the adsorption of other thiol collectors on metal and sulfide mineral surfaces. An estimate is made of the potential dependence of the interaction of IPETC with chalcocite.     

Synthesis and structure of the rhodium complex [Ph3MeP][RhBr4(DMSO)2-trans]

The ionic complex, methyltriphenylphosphonium(I) trans-bis(dimethylsulfoxido)tetrabromorhodiate, was prepared by the reaction of sodium hexabromorhodiate with methyltriphenylphosphonium bromide in dimethyl sulfoxide and studied by X-ray diffraction. The phosphorus atom in the [Ph₃MeP]⁺ cation has an almost undistorted tetragonal coordination (the CPC angles are 108.3(2)°–110.5(2)°, the P-C bonds are 1.779(6)–1.798(4) Å). In the octahedral complex anion [RhBr₄(DMSO)₂-trans]^?, the dimethyl sulfoxide ligands are coordinated by the sulfur atoms (Rh-S, 2.344(1), 2.336(1); Rh-Br, 2.4839(7)–2.4934(7) Å; SRhS, 179.56(7)°; trans-BrRhBr, 179.30(3)°, 179.56(7)°) (CIF file CCDC no. 978748).     

Synthesis, characterization, and SAMs electroactivity of ruthenium complexes with sulfur containing ligands

The vibrational and ¹H NMR data hints that the coordination of the 2,2′-dithiodipyridine (2-pySS) ligand to the [Ru(CN)₅]³⁻ metal center occurs through the sulfur atom instead of the nitrogen atoms which is usually observed for N-heterocyclic ligands. Electrochemical results show that this coordination mode implies an additional thermodynamic stabilization of the Ru^II over Ru^III oxidation state due to a relative stronger π-back-bonding interaction with the empty low-lying dπ orbitals of the sulfur atom. Computational data reinforce the experimental results showing that the 2-pySS Lewis base centers are located on the sulfur atoms. Ligands containing only sulfur atoms as coordination sites (2,2′-dithiodipyridine N-oxide (2-pySSNO), 1,4-dithiane (1,4-dt), and 2,6-dithiaspiro[3.3]heptane (asp)) were also coordinated to the [Ru(CN)₅]³⁻ metal center to undoubtedly correlate the electrochemical results with the ligand coordination atom. Among the synthesized compounds, the [Ru(CN)₅(1,4-dt)]³⁻ and [Ru(CN)₅(asp)]³⁻ complexes showed to be able to form self-assembled monolayers (SAMs) on gold. These SAMs, which were characterized by SERS (surface-enhanced Raman scattering) spectroscopy, successfully assessed the heterogeneous electron transfer reaction of the cytochrome c metalloprotein in physiological medium.     

Oxidative transformation of ciprofloxacin by alkaline permanganate – A kinetic and mechanistic study

This spectroscopic study presents the kinetics and degradation pathways of oxidation of ciprofloxacin by permanganate in alkaline medium at constant ionic strength of 0.04 mol⁻³. Orders with respect to substrate, oxidant and alkali concentrations were determined. Effect of ionic strength and solvent polarity of the medium on the rate of the reaction was studied. The oxidation products were identified by LC-ESI-MS technique. Product characterization of ciprofloxacin reaction mixtures indicates the formation of three major products corresponding to m/z 263, 306, and 348 (corresponding to full or partial dealkylation of the piperazine ring). The piperazine moiety of ciprofloxacin is the predominant oxidative site to KMnO₄. Product analyses showed that oxidation by permanganate results in dealkylation at the piperazine moiety of ciprofloxacin, with the quinolone ring essentially intact. The reaction kinetics and product characterization point to a reaction mechanism that likely begins with formation of a complex between ciprofloxacin and the KMnO₄, followed by oxidation at the aromatic N1 atom of piperazine moiety to generate an anilinyl radical intermediate. The radical intermediates subsequently undergo N-dealkylation. Investigations of the reaction at different temperatures allowed the determination of the activation parameters with respect to the slow step of proposed mechanism. The proposed mechanism and the derived rate laws are consistent with the observed kinetics.     

Reaction Equilibrium and Kinetics of Synthesis of Polyoxymethylene Dimethyl Ethers from Formaldehyde and Methanol

Polyoxymethylene dimethyl ethers (PODE _n ) are environmentally friendly diesel fuel additives. They belong to alkyl ethers that could reduce solid particulate matter formation and emissions of carbon monoxide and nitrogen oxide when added into diesel fuels. This work aimed to researching chemical equilibrium and reaction kinetics of the synthesis of polyoxymethylene dimethyl ethers from formaldehyde and methanol catalyzed by an ion-exchange resin at the reaction temperatures 313, 333, 343 and 353 K. In the reversible reaction, the K_{n ≥ 2}/K₂ ratio was equal to one. The reaction orders of methanol, formaldehyde, water and PODE _n were 0.2638, 0.1328, 0.1565 and 0.0048, respectively. At a 10 wt % dosage of H-SIR1 resin, the rate constants of the methylal (dimethoxymethane) formation and depolymerization were 1.04 × 10⁴ and 3.43 × 10⁶ min^–1, respectively, and the pre-exponential factor for the PODE_{n + 1} formation was 2.50 × 10³ min^–1. Activation energies for the methylal propagation and depolymerization and PODE_{n > 1} formation were 30.46, 48.40 and 27.10 kJ/mol, respectively. The results indicated that the equilibrium constants of PODE_{n > 1} formation reactions were consistent. The exothermic reaction of methylal formation was easier than the reverse reaction and more difficult than the formation of PODE_{n > 1}.     

Kinetics and mechanism of oxidation of dimethyl sulfide with molecular oxygen catalysed by K[RuIII(EDTA-H)Cl] complex in water-dioxan medium

Oxidation of dimethyl sulfide (Me₂S) with molecular oxygen catalysed by [Ru^III(EDTA)(H₂O)]⁻1a (EDTA = ethylenediaminetetraacetate anion) was studied spectrophotometrically in water-dioxan medium at constant pH 5.0 (acetic acid-acetate buffer) and ionic strength 0.2 M (KCl). The reaction proceeds through the formation of a [Ru^III(EDTA)(Me₂S)]⁻2 intermediate which undergoes oxidation with molecular oxygen to give dimethyl sulfoxide (Me₂SO) as the oxidation product. The rate of formation of 2 and its decomposition was followed spectrophotometrically by monitoring the reactions at 528 nm the characteristic peak of 2. The rate of formation of 2 was found to be first order in the concentrations of 1a and Me₂S. The rate of decomposition of 2 is independent of the concentration of Me₂S and is half-order with respect to oxygen concentration. Both the formation and decomposition reactions of 2 were studied at different temperatures, and the activation parameters ΔH≠ and ΔS≠ were determined. A suitable mechanism was proposed for the catalytic oxidation of dimethyl sulfide to dimethyl sulfoxide with molecular oxygen.     

First example of the Mislow-Braverman-Evans rearrangement retaining the sulfur atom on the original carbon

Treatment of 1-chloro-2-methylalkenyl p-tolyl sulfoxides with N-lithio 2-piperidone in THF at room temperature resulted in the formation of 1-chloro-2-(hydroxymethyl)alkenyl p-tolyl sulfides in good yields. This reaction is the first example of the Mislow-Braverman-Evans rearrangement retaining the sulfur atom on the original carbon.     

Reactivity of fluorinated sulfur-containing heterocycles towards nucleophilic and oxidizing reagents

The reaction of 5,5-bis(trifluoromethyl)-6-thia-bicyclo[2.2.1]hept-2-ene, 5,5-bis(trifluoromethyl)-6-thia-bicyclo[2.2.2]oct-2-ene and 2,2-bis(trifluoromethyl)-3,6-dihydro-4,5-dimethyl-2H-thiopyran with i-C₃H₇MgCl leads to the formation of ring opening products as the result of nucleophilic attack of the Grignard reagent on the sulfur atom. According to DFT calculations the reactivity of the sulphur-containing substrate correlates with the strain energy of the heterocycle. The oxidation of 3-thia-4,4-bis(trifluoromethyl)tricyclo[5.2.1.0^2,5]non-7-ene by hydrogen peroxide in hexafluoro-iso-propanol solvent resulted in formation of the corresponding sulfoxide however, the reaction with m-chloroperoxybenzoic acid produced the product of exhaustive oxidation of sulfur and the double bond. In sharp contrast, the oxidation of 5,5-bis(trifluoromethyl)-6-thia-bicyclo[2.2.1]hept-2-ene and 5,5-bis(trifluoromethyl)-6-thia-bicyclo[2.2.2]oct-2-ene by MCPBA (2d, 25 °C) proceeds with the preservation of the double bond, leading to the selective formation of the corresponding sulfones.