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Mechanism for the reactions of sulfides and sulfoxides with hypochlorites: Racemization and oxygen exchange of oxysulfonium salts and sulfoxides
... Recently, we have proposed [25] a different mechanism for the reaction of sulfides with hypochlorites (R′OCl, R ′ = H, Me, and t-Bu), involving the attack of the sulfur atom of sulfides at the oxygen atom of hypochlorites (Equation (6)). The formation of oxysulfonium cations (R 2 SOR′ + ) takes place with the leaving of Cl − , in S N 2 type transition state (TS). ...
... The attack of sulfide at chlorine of R′OCl, the formation of R 2 SCl + was excluded, because DFT computations indicated that the reaction has very high energy of activation. [25] ...
... The calculated total and free energy of activation of water-assisted multistep chlorination of Me 2 S with HOCl are ΔE ‡ = 40.1 kJ mol −1 and ΔG ‡ = TABLE 1 Selected net Mulliken atomic charges (Q, a.u.), atomic distances (R, Å), and bond angels (θ, degree) for species formed in the chlorination of Me 2 S (1a) with HOCl (2, Schemes 1 and 2). Calculations were performed at DFT(B3LYP)/6-31G (d) level of theory in water, at 25°C 56.7 kJ mol −1 , while those of the simple one-step oxygen transfer reaction between the Me 2 S and HOCl reactants [25] are ΔE ‡ = 14.0 kJ mol −1 and ΔG ‡ = 57.4 kJ mol −1 (Equation (6); R = Me, R′ = H). ...
DFT computations have been performed to study the mechanism of the reactions of sulfides with hypochlorous acid and N ‐chlorosulfonamides. Sulfides can attack HOCl both at chlorine and oxygen atoms. The attack at chlorine results in the formation of chlorosulfonium cation (R 2 SCl ⁺ ) and OH ⁻ intermediates, which transform to sulfoxide product. The high free energy of activation (Δ G ‡ ), which is needed for the formation of ionic intermediates, is decreased considerably by solvation in protic solvents. Since the attack of sulfides at the oxygen atom of HOCl has low Δ G ‡ value, the chlorination of sulfides can compete with the attack at the oxygen atom only in protic solvents. Kinetic studies showed that the reactivity of species, formed from N ‐chlorosulfonamides in protic solvents, increases in the course: RSO 2 NCl ⁻ << RSO 2 NHCl < < RSO 2 NCl 2 . The chlorination of sulfides with RSO 2 NHCl or RSO 2 NCl 2 results in the formation of R 2 SCl ⁺ and RSO 2 NH ⁻ or RSO 2 NCl ⁻ intermediates, respectively, and the computed and experimentally derived Δ G ‡ data agree in these cases. Sulfilimine (R 2 S═NSO 2 R) and sulfoxide products are formed in the reaction of R 2 SCl ⁺ with RSO 2 NH ⁻ and water, respectively. Acyloxy‐chloro‐λ ⁴ ‐sulfane intermediates are produced in the reactions of N ‐chlorosulfonamides and sulfides, bearing 2‐carboxy‐phenyl group, without the intermediacy of chlorosulfonium cations. Explicit water molecules must also be included in computations for reactions proceeding with formation or destruction of ions, to get Δ G ‡ values, comparable with experimental data.
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... Some researchers have discussed the oxidation of sulfites, sulfoxides, and alcohols by HOCl in organic media and under nonphysiological conditions of temperature, pH, and reactant concentration [14][15][16][17]. The reaction mechanisms reported by these authors have helped us to explain, at least in part, the HOCl scavenging ability of the six vehicles by using the TMB assay under physiological conditions of pH and ionic strength. ...
... On the other hand, the reaction of methionine with HOCl produces a sulfonium chloride that subsequently undergoes hydrolysis, giving the sulfoxide as final product [19]. In addition, the hypochlorite anion and HOCl oxidize sulfides to sulfoxides and sulfoxides to sulfones; in these reactions, the oxygen atom of the reactants attacks the sulfur atom of the substrates [16,17]. ...
... In acetic acid, sodium hypochlorite oxidizes secondary alcohols to ketones faster than it oxidizes primary aliphatic alcohols to aldehydes and esters [14,15]. HOCl can also chlorinate alcohols and produce alkyl hypochlorites, which hydrolyze to HOCl and alcohols in the reverse reaction [17]. ...
... While chlorosulfonium-containing salts can be isolated from aprotic solutions, 25 the chlorosulfonium ion intermediate in an oxidation reaction has never been directly observed in the aqueous phase. 15,26,27 To address this issue, Ruff et al. explored the oxidation of sulfides by hypochlorites with density functional theory (DFT) calculations and found that the barrier for chlorosulfonium formation is very high in the absence of solvent. 27 This led the authors to propose a more energetically favorable pathway that proceeds via direct attack by the oxygen atom of HOCl to form a hydroxysulfonium (4) species (Scheme 1b). ...
... 15,26,27 To address this issue, Ruff et al. explored the oxidation of sulfides by hypochlorites with density functional theory (DFT) calculations and found that the barrier for chlorosulfonium formation is very high in the absence of solvent. 27 This led the authors to propose a more energetically favorable pathway that proceeds via direct attack by the oxygen atom of HOCl to form a hydroxysulfonium (4) species (Scheme 1b). This species may then yield the sulfoxide product through deprotonation by either Cl − or H 2 O. ...
The oxidation of the amino acid methionine (Met) by hypochlorous acid (HOCl) to yield methionine sulfoxide (MetO) has been implicated in both the interfacial chemistry of tropospheric sea spray aerosols and the destruction of pathogens in the immune system. Here, we investigate the reaction of deprotonated methionine water clusters, Met-·(H2O)n, with HOCl and characterize the resulting products using cryogenic ion vibrational spectroscopy and electronic structure calculations. Capture of the MetO- oxidation product in the gas phase requires the presence of water molecules attached to the reactant anion. Analysis of its vibrational band pattern confirms that the sulfide group of Met- has indeed been oxidized. Additionally, the vibrational spectrum of the anion corresponding to the uptake of HOCl by Met-·(H2O)n indicates that it exists as an "exit-channel" complex in which the Cl- product ion is bound to the COOH group following the formation of the S═O motif.
... Kabeya et al. (2013) observed the antioxidant interference of DMSO in assays involving capture of HOCl. Studies suggest that the presence of the sulphur atom in the molecule favours the oxidation of DMSO by HOCl (Peskin and Winterbourn, 2001;Ruff et al., 2012), directly influencing the results. ...
Coumarins are phenolic compounds and have various biological properties, including antioxidant activity. The isocoumarin paepalantine, isolated from of Paepalanthus bromelioides Silveira, Eriocaulaceae, exhibits a wide range of biological activities, including antimicrobial, anti-inflammatory, antioxidant and cytotoxic properties. Studies on paepalantine often use dimethylsulfoxide as a solvent. However the dimethylsulfoxide interferes with antimicrobial, cytotoxic and antioxidant assays. Thus, this study aims to evaluate alternative solvents for paepalantine and evaluate their potential to interfere with antioxidant assays (ABTS+, O2−, HOCl). Of the selected solvents, propylene glycol had good solubility and remained stable throughout the study period. The results suggested that there is no interference from propylene glycol in antioxidant assays, while dimethylsulfoxide significantly interfered with the HOCl assay. The antioxidant assays showed that paepalantine demonstrated similar or even better antioxidant activity than Trolox. Thus, propylene glycol may be the solvent of choice for paepalantine, a compound that has significant biological potential.
... However, this latter process was highly dependent upon the concentration of the chloride ion, which presumably generated sulfur oxychloride intermediates, and had to occur in organic solvents such as benzene, nitrobenzene, dioxane or tetrahydrofuran. The presence of water drastically retarded the reaction (Mislow et al., 1964;Ruff et al., 2012). In general, the energy requirement for alteration around the sulfur stereogenic centre is sufficiently high (e.g. ...
1. Incubation of beagle hepatic cytosol, under conditions promoting phenylalanine hydroxylase activity, led to the formation of the sulfoxide derivatives of S-carboxymethyl-l-cysteine, N-acetyl-S-carboxymethyl-l-cysteine, S-methyl-l-cysteine and N-acetyl-S-methyl-l-cysteine. Thiodiglycolic acid was not a substrate. Enzyme kinetic parameters (Km, Vmax) were derived indicating S-carboxymethyl-l-cysteine had the greatest clearance; no enantioselective preference was observed for this S-oxygenation reaction. 2. Following oral administration of S-carboxymethyl-l-cysteine to beagle dogs, the parent substance and its sulfoxide were the only compounds identified in the plasma. Pharmacokinetic data have been obtained indicating that the small amount of sulfoxide formed persisted within the body for longer than the parent material, but that the majority of the ingested dose remained in the administered sulfide form. 3. The sulfide moiety within the muco-regulatory drug, S-carboxymethyl-l-cysteine, is thought to be vital as it acts as a free radical scavenger, resulting in the inactive sulfoxide. Additional extensive enyzme-mediated sulfoxidation would decrease the amount of active sulfide available. In the dog this appears to not be an issue, signalling possible exploitation for therapeutic benefit in treating airway disease.
Herein is reported the development of a continuous flow generator that produces highly reactive organic hypochlorites for the chemical neutralization of sulfur-based chemical warfare agent (CWA) simulants. The generator relies...
A theoretical study simulating the hypohalogenation reaction of cysteine (CSy) and N-acetylcysteine (NAC) has been performed with the objective of obtaining the energetic, electronic and kinetic properties for the reactions at room temperature and body temperature and considering neutral and basic conditions in aqueous medium. The study has been performed using the M06-HF, M06-2X, MPWB1K, BHANDHLYP density functional methods and with the MP2 method along with either the 6-311+G(d, p) basis set or the extended 6-311++G(3df,3pd) basis set. The results of the study indicate that all reactions proceed through the formation of the reactant complex structure, which is stabilised by the formation of intermolecular hydrogen bond between the reactant species. The reactions are also thermodynamically preferred to take place at room temperature. The reaction involving hypochlorous acid is faster and more thermodynamically preferred to the reaction involving hypochlorite anion, both at room temperature and at body temperature. The relative magnitude for the rate constant involving CSy and NAC is dependent on the pH of the solution. A comparison of the calculation methods utilised for the study suggests that the best methods for estimation of the rate constant are those containing both the HF-like exchange and the kinetic density components.
Recent work reviews on the kinetics and mechanisms of oxidation by pyridinium and quinolinium halochromates. A mechanism involving the protonated nitrone as reactive species has been proposed. Mechanism suggests involving decomposition of reductant-BIDC complexes via a cyclic transition state to give carbocationic species through hydride ion transfer from the reductant to the oxidant. Kinetic and activation parameters for oxidation are determined by allyl and alcohol with Waugh-type enneamolybdomanganate(IV). Variety of sulfides and dibenzothiophene are oxidized to the corresponding sulfoxide or sulfone in high yields with mononuclear as well as dinuclear diperoxo complexes of tungsten as oxidants. Heck-type CDC reaction of indolizines with electron-deficient alkenes produces 3-alkenyl-substituted indolizines. Various aspects of this reaction are historical perspective, reaction mechanism, variation and improvements, synthetic utility, and experimental details for the enantioselective preparation of epoxides.
The oxidation of organic sulphides with aqueous hydrogen peroxide in ionic liquids (ILs) and catalysed by oxodiperoxomolybdenum complexes was investigated. The selective formation of several sulfones was achieved by using the 1:3 ratio of sulphide:H2O2 in [C4mim][PF6] (C4mim = 1 butyl-3-methylimidazolium) in a reaction catalysed by [Mo(O)(O2)2(H2O)n] complex. Conversely, sulfoxides were produced with good selectivities by using a 1:1 ratio in the same solvent in a 1h reaction with [Mo(O)(O2)2(Mepz)2] (Mepz = methylpyrazol). The use of [C4mim][PF6] as solvent was advantageous for two reasons: i) the improved performance of the H2O2/IL combination; ii) recycling of the catalyst/IL mixture without a significant diminution of conversion or selectivity. A DFT analysis using the [Mo(O)(O2)2(L)] catalysts (L = Mepz, a; 3,5 dimethylpyrazol, dmpz, b; and H2O, c) indicated that a Sharpless type outer sphere mechanism is more probable than a Thiel type one. The highest barrier of the catalytic profile was the oxo-transfer step, in which the nucleophilic attack of sulphide into the peroxide ligand occurred with formation of dioxoperoxo species. In order to yield the sulfoxide and the starting catalyst, the oxidation of the resulting dioxoperoxo species with H2O2 was found to be the most favourable pathway. Subsequently, the sulfoxide to sulfone oxidation was produced through a similar mechanism involving the [Mo(O)(O2)2(L)] catalyst. The comparable energies found for both the successive two oxo-transfer steps were in agreement with the experimental formation of sulfone in both the reaction with an excess of oxidant and the stoichiometric one in the absence of oxidant. In the latter case, diphenylsulfone was isolated as the major product in the 1:1 combination of diphenylsulphide and [Mo(O)(O2)2(Mepz)2] in the ionic liquid [C4mim][PF6]. Also, the compounds [HMepz]4[Mo8O26(Mepz)2]•2H2O, 1, [Hdmpz]4[Mo8O26(dmpz)2]•2dmpz, 2, and [Hpz]4[Mo8O22(O2)4(pz)2]•3H2O, 3, were obtained by treating in water, stoichiometrically, dimethylsulfoxide and the corresponding [Mo(O)(O2)2(L)2] complex (L = Mepz; 3,5 dimethylpyrazole, dmpz; pyrazol, pz). The crystal structures of octanuclear compounds 1-3 was an indirect proof of the formation of the theoretically proposed intermediates.
A new algorithm is presented for obtaining points on a steepest descent path from the transition state of the reactants and products. In mass‐weighted coordinates, this path corresponds to the intrinsic reaction coordinate. Points on the reaction path are found by constrained optimizations involving all internal degrees of freedom of the molecule. The points are optimized so that the segment of the reaction path between any two adjacent points is given by an arc of a circle, and so that the gradient at each point is tangent to the path. Only the transition vector and the energy gradients are needed to construct the path. The resulting path is continuous, differentiable and piecewise quadratic. In the limit of small step size, the present algorithm is shown to take a step with the correct tangent vector and curvature vector; hence, it is a second order algorithm. The method has been tested on the following reactions: HCN→CNH, SiH2+H2→SiH4, CH4+H→CH3+H2, F−+CH3F→FCH3+F−, and C2H5F→C2H4+HF. Reaction paths calculated with a step size of 0.4 a.u. are almost identical to those computed with a step size of 0.1 a.u. or smaller.
DFT computations have been performed in acetone and water solvents in order to investigate the mechanism of hydrolysis of acid chlorides. Acetyl chloride and chloroacetyl chloride hydrolyze via concerted, one-step SN2 mechanism, with the attack of water at the sp2 hybridized carbon atom of the CO group, and the transition state (TS) has distorted tetrahedral geometry. Solvent molecules act as general base and general acid catalysts. The TS of chloroacetyl chloride is tighter and less polar than the TS of acetyl chloride. The structure of the SN2 TS for the hydrolysis of benzoyl chlorides changes with the substituents and the solvent. Tight and loose TSs are formed for substrates bearing electron withdrawing (e-w) and electron donating (e-d) groups, respectively. In acetone, only the e-w effect of the substituents increase the reactivity of the substrates, and the change of the structure of the TSs with the substituents is small. In water, polar and very loose TSs are formed in the reactions of benzoyl chlorides bearing e-d substituents, and the rate enhancing effect of both e-d and e-w groups can be computed at higher level of theory. Calculated reactivities and the changes of the structure of the TSs with substituents and solvent are in accordance with the results of kinetic studies. In SN2 nucleophilic substitutions late/early TSs are formed if the attacking reagent is poorer/better nucleophile than the leaving group, and loose/tight TSs are formed for substrates bearing e-d/e-w substituents and in protic/aprotic solvents. Copyright © 2010 John Wiley & Sons, Ltd.
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Thiane and thiolane derivatives with 2-methyl, 2-ethyl, 2-isopropyl and 2-tert-butyl groups were prepared and converted to cis and trans sulphilimines and sulphoxides by various stereoselective methods. Cis-sulphilimines were formed by using t-BuOCl and TsNH- in a two-stage process, while cyclic sulphides were converted by chloramine-T predominantly to trans-sulphilimines. Sulphoxides enriched in cis and trans isomers were obtained by different methods of oxidation. Diastereoisomeric product distributions were measured by hplc and the configurations of diastereoisomers were assigned by 13C NMR spectroscopy. Preferred conformations of sulphilimines were determined by analysis of 13C NMR and X-ray data. As shown by 13C NMR spectra, the conformations of sulphilimines and sulphoxides are analogous.
The conversion of alkylthiolanes and alkylthianes by tert-butyl hypochlorite in methanol yields an equilibrium mixture of cis- and trans-methoxysulfonium chlorides. The corresponding methoxysulfonium tetrafluoroborates prepared from sulfoxides by O-alkylation show equilibration and methoxy exchange in methanol containing chloride ions. The rate constants have been determined by 1H NMR measurements, and an SN(Ad+E) mechanism is proposed for these reactions. Both the greater thermodynamic stability of the cis isomers and the greater reactivity of the trans analogues are explained by stereoelectronic effect of σ(CH) - σ*(SX) type with X OMe or Cl.
The formation of tert.-butyl hypochlorite from the alcohol and hypochlorous acid and its hydrolysis have been investigated in a series of buffer solutions ranging in pH from 6.3 to 2.7. By the use of 18O as tracer it has been shown that in both reactions the bond between the tert.-butyl group and the oxygen atom remains intact. Kinetic investigations showed the reaction to be subject to general acid-base catalysis. The rate coefficients for a number of catalysts have been determined. A mechanism of these reactions is postulated involving various active intermediates such as H2OCl+, acetyl hypochlorite, and other related compounds of the type ACl, where A is the anion of any general acid. The relationship between the reactions of tert.-butyl hypochlorite and those of hypochlorous acid is discussed.
The mechanistic investigations of the concurrent oxygen exchange and racemization reactions of 18O-labeled and optically active methyl p-tolyl sulfoxide (I) and phenyl p-tolyl sulfoxide (II) in sulfuric acid of various concentrations have been carried out by the determination of detailed kinetics. The kinetic data were analyzed in the lights of kex⁄krac values, activation parameters, correlations between the rates and acidity functions, solvent isotope effects, polar effects of substituents, etc.. A gradual change of mechanism of the reaction from an SN2 type process to a predominant A-1 like one (in above 95% sulfuric acid) with the increase of the concentration of sulfuric acid was observed. All these observations suggest that the A-1 like reaction takes place through a cation radical (–\overset+·S–) or a dication (–\overset++S–) intermediate at higher concentrations of sulfuric acid, while the SN2 type reaction that involves a water molecule as nucleophile in the rate-limiting step is the predominant path in less concentrated sulfuric acid.
The oxidation of thioethers with hypochlorite using a two phase system is investigated. The following parameters are varied: (a) the pH-value, (b) the concentration of hypochlorite (c) the participation of phase transfer catalysts (d) the structure of the thioethers and (e) the behaviour of the organic phase. The rate of the oxidation of thioethers in acetic esters is accelerated by the pH-decrease initiated by the hypochlorite catalyzed hydrolysis of the esters.Die Oxidation von Thioethern mit Hypochlorit im Zweiphasensystem wird in Abhängigkeit von folgenden Parametern untersucht: (a) vom pH-Wert, (b) der Konzentration an Hypochlorit (c) unter Mitwir-kung von Phasentransfer-Katalysatoren (d) der Struktur der Thioether und (e) vom Verhalten der organischen Phase. Die Oxidation der Thioether verläuft in Essigsäureestern am schnellsten, verursacht durch eine von Hypochlorit katalysierte Esterspaltung, die über eine Absenkung des pH-Wertes zu einer Beschleunigung der Oxidation führt.
The mechanism of the concurrent oxygen exchange and racemization reactions of sulfoxides with chloride ion in sulfuric acid 64.7–80.2% has been studied. We have found that the rate of oxygen exchange of O-labeled and optically active phenyl p-tolyl sulfoxide becomes identical to that of racemization by the addition of at least 0.08 mol/l potassium chloride to sulfuric acid media. The rate of the racemization cannot be correlated with HA, and the steric effect of substituent is not very large. Based on these observations, a mechanism (Scheme II) which does not include the rate-limiting formation of the chlorosulfonium ion intermediate may be suggested as most plausible for the reaction.
2-Alkylthianes react with tert-butyl hypochlorite to give trans-1-tert-butoxythianium salts which are hydrolyzed to trans-2-alkylthiane 1-oxides with high stereoselectivity.
The kinetics of the oxidation of RSAr, R2S, and (CH2)nS sulphides with NaIO4yielding sulphoxides were investigated in ethanol–water solutions, and the rate equation v=k2[sulphide][IO4–] was found to be valid. The observed substituent (ρ– 1.40 for YC6H4SMe; ρ*–1.06 and –0.60 for RSPh and R2S, respectively) and solvent effects (m 0.722 for MeSPh) are explained by an electrophilic attack of periodate oxygen on sulphide, leading to a polar transition state. The slight steric requirements of the reaction (δ 0.27 and 0.105 for RSPh and R2S, respectively) and the lack of solvent isotope effect exclude the participation of water in an SN2-type nucleophilic displacement on a sulphonium centre, which might be considered to have been formed from sulphide and periodate in a fast pre-equilibrium. A moderate anchimeric assistance was observed for the conversion of XC6H4SMe sulphides with o-X =CO2Me, CO2H, and CO2–(k2°/k2pca. 1). From the results it is concluded that oxidation proceeds by a one-step electrophilic oxygen transfer from IO4– to sulphide through a polar product-like transition state that is stabilized by a polar neighbouring group or by the increasing polarity of the medium.
The stereochemical course of the reaction of optically active diarylethoxysulphonium salts with halide ions to give sulphoxides depends on the nature of the halide. For chloride, bromide, and iodide ions the reaction proceeds with retention of configuration at sulphur, whereas for fluoride ions net inversion is observed; this is tentatively explained on the basis of nucleophilic substitution involving apical attack by fluoride ion and equatorial departure of the leaving group, or of Berry pseudorotation.
DFT computations on the mechanisms of nucleophilic substitutions on benzyl bromides were performed and the calculated activation parameters were compared with experimentally acquired data. In vacuo, the presence of electron-withdrawing (e-w) groups on the benzyl bromides accelerated the reactions and the calculated ΔG‡/ΔH‡/ΔS‡ vs. σ plots were linear, while in solvents there were breaks in the calculated and measured ΔG‡/ΔH‡ vs. σ+ plots of the reactions between the benzyl bromides and Br–, both with electron-donating (e-d) and with e-w substituents accelerating the reactions. The calculated ΔS‡ values appeared to be independent of the substituents. In solvents, the calculated ΔG‡/ΔH‡/ΔS‡ vs. σ+ plots for the reactions between benzyl bromides and pyridine were linear, whereas breaks were observed in the plots of the measured data. These reactions were promoted by e-d substituents, but the measured reactivities of substrates bearing e-w groups were higher than expected. No breaks in the ΔG‡/ΔH‡/ΔS‡ vs. σ plots were observed when the substituents on the pyridine nucleophile were changed. The best agreement between the calculated and measured values was obtained for the least solvent-dependent ΔG‡ parameter. The experimentally measured ΔS‡ and ΔH‡ data were influenced by the rearrangement of the solvent molecules. The calculated structural parameters of the transition states (TSs) varied linearly with the substituent constants, with loose and tight distorted trigonal-bipyramidal TSs being formed by benzyl bromides bearing e-d and e-w groups, respectively. The reactions proceeded by SN2 mechanisms; only the transition structures were changed with the substituents and the media. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Reactions of thianes andcis-andtrans-1-thiadecalins with 4-chloroaniline andN-chlorsuccinimide ortert-butylhypochlorite gave configurationally homogeneous cyclicN-4-chlorophenyl sulfimides. With appropriately substituted sulfides conformationally homogeneous thiane-and cis-1-thiadecalin-1-imides were obtained. Formation of sulfimides with axially oriented S-N bond is strongly disfavoured. Reactions with conformationally rigid ring systems yielded only sulfimides with equatorial S-N bond; two isomeric sulfimides, both with equatorial S-N bond, were obtained with the mobilecis-1-thiadecalin. Sulfimides with axial S-N bond were prepared from conformationally rigid sulfoxides with equatorial S-O bond. It is assumed that formation of sulfimides with rigid ring systems proceeds viaN-chloroanilines, while reactions of conformationally mobile systems withN-chlorosuccinimide may also occur via intermediate succinimidyl sulfonium ions.
A range of sulfides can be selectively oxidized to the corresponding sulfoxides in good yields using NaClO/H2SO4 in both water and 50:50 water:EtOH as solvent. Two new compounds are reported that show a diastereoselective oxidation in 2-phenylthioalcohols with possible neighboring hydroxyl group participation with a logic proposed mechanism.
DFT computations have been performed at different levels of theory to identify the mechanism for the oxidation of sulfides and sulfoxides with periodates. The periodate ion (IO4–), periodic acid (HIO4) and their hydrated derivatives all oxidize sulfides to sulfoxides in one-step oxygen-transfer reactions and the relative reactivities are HIO4 >> H5IO6 > IO4– > H4IO6– >> H3IO62–. The hydration and dissociation equilibria of the periodates are shifted towards IO4– in neutral and moderately acidic solutions, and sulfides are oxidized mainly with IO4– under normal experimental conditions. The oxygen atoms of the periodates attack the sulfides perpendicularly to the plane of the C–S–C atoms and the S···O···I atoms are in a linear arrangement in the very early transition state (TS). The sulfides are the electron donors and periodates are the electron acceptors in the reactions; the geometries of the TSs are determined by the overlap of the HOMO and the LUMO of the reactants. Other mechanisms can be ruled out because the attack of the sulfur atom of the substrate on the iodine atom of the reactants increases the energy of the system continuously very steeply as the S···I distance decreases. Experimentally derived ΔG‡ values are in good agreement with the ΔG‡ data computed for the oxygen-transfer mechanism. Sulfoxides are also oxidized to sulfones with IO4– in a one-step oxygen-transfer reaction, and the structures of the TSs and the ΔG‡ data are similar to those obtained for the reactions of sulfides. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Molecules rearrange by regular and irregular processes. The former occur with preservation of bonds and coordination numbers while the latter involve rupture and reformation of bonds via states possessing different coordination numbers. For molecules with skeletons that carry n ligands both processes can be represented by permutation operators belonging to the symmetrical group Sn. These operators are obtained from the descriptors of the particular molecules in a simple manner; the conceivable reaction mechanisms correspond to the skeletal symmetry subclasses of Sn. Regular rearrangements—e.g. of phosphorane derivatives with a monocentric skeleton, including their analogs, or of ethane derivatives with a dicentric skeleton—all submit themselves to classification based upon skeletal non-rigidity. Flexible molecular skeletons are representable by a collection of rigid skeletal models which can be interconverted by deformations of bond angles and/or some form of internal rotation. To accomplish mechanistic understanding of these regular processes, it is useful to represent the symmetries of the rigid skeletal models and the existent ligand equivalencies by subgroups of Sn and consider the dependence of the skeletal flexibility upon the given ligand set. This procedure is based on the ideas of Polya and Longuet-Higgins. The former introduced separation of permutational molecular symmetry into skeletal symmetry and ligand set symmetry, which, combined with the total molecular symmetry concept developed by Longuet-Higgins for the treatment of non-rigid symmetric molecules, yield the foundation for the following classification of regular pentacoordinate rearrangements and related processes. It will be shown that with the given quantum chemical properties of the pentacoordinate phosphorus bond system, including participation of the P3d orbital set, not only the BPR‘2’ mechanism but also single and multiple TR[2] processes must be considered in the interpretation of the observed phenomena. Although some experimental observations can be interpreted by either of the two mechanisms, and certain other regular rearrangements can be explained only by invoking the TR mechanism, no regular processes are known, as yet, that can be explained solely by the BPR mechanism.
Alkyl aryl sulphoxides are reduced by dialkyl sulphides in 2 : 1 methanol–water in the presence of 4M-HCl. The kinetics of the reaction between p-chlorophenyl methyl sulphoxide and dibutyl sulphide and the basic properties of the sulphoxide have been investigated in detail. Reaction orders, acid catalysis, and comparison of the reduction rate with that of the loss of optical activity by the (+)-R-sulphoxide indicate a predominant role for the chlorosulphonium cation. A mechanism is suggested in which the changes of the oxidation states occur through the reaction between the sulphide and this intermediate.
Treatment of the important electrostatic effects of solvation by means of reaction field theory is becoming common in electronic structure calculations on molecules. Most extant reaction field methods neglect or crudely approximate the often important influence of volume polarization arising from solute charge that quantum mechanically penetrates outside the cavity that nominally encloses it. This work proposes and examines a new formulation that provides an accurate simulation of volume polarization effects while being much simpler to implement and use than an exact treatment. Detailed comparisons with other related methods are also given. © 2000 American Institute of Physics.
© 2001 American Institute of Physics.
A set of rules for determining the atomic radii of spheres used to build the molecular cavities in continuum solvation models are presented. The procedure is applied to compute the hydration free energy for molecules containing H, C, N, O, F, P, S, Cl, Br, and I at a computational level (Hartree–Fock with a medium size basis set) allowing the study of relatively large systems. The optimized radii reduce the mean error with respect to the experimental solvation energies below 0.20 kcal/mol for a set of 43 neutral solutes and around 1 kcal/mol for 27 ions. Moreover the correct trends are observed for the solvation energies of homolog series, like the series ammonia–trimethylamine, that are not correctly reproduced by usual solvation models. © 1997 American Institute of Physics.
The oxidation of organic sulphides (n-Bu2S, PhSCH3, Tolyl-SCH3, p-Cl-C6H4SCH3, and Ph2S by (HMPT)CrO(O2)21′ in CHCl3 has been studied. The reaction produces the corresponding sulphoxides in nearly quantitative yields according to a 2:1 stoichiometry of sulphide to metaldiperoxide. A second-order-overall (order one in each of the reagents) kinetic law is obeyed. In parallel, the oxidation of organic sulphides by (HMPT)MoO(O2)21' has been studied. Kinetic data, the observed rate laws, and the effect of inhibitors (HMPT, DABCO) have pointed out that-although 1' is significantly more reactive than 1′—considerable similarity exists between the two metaldiperoxides, in that both appear to act as electrophilic oxidizers. Also, through 1H, 31P and 13C NMR investigations have permitted to assess the relevance of equilibria (HMPT)MO(O22 MO(O2)2 + HMPT [with M = Mo(VI) or Cr(VI)]in solution, whereas no NMR evidence could be found for significant substrate coordination under the given conditions.
The oxidation with t-butyl hypochlorite of a number of sulfides of the general structure RSCH2R′ is described. In methanol or ethanol as solvents and R′ = ethynyl or carbomethoxy groups, no sulfoxide was formed; instead, almost complete conversions to the corresponding α-methoxy- or α-ethoxy-substituted compounds were observed. In the case of R′ = phenyl, mixtures of the α-substituted products with sulfoxides were obtained, whereas with R′ = alkyl, sulfoxides were the sole products. In t-butyl alcohol as solvent, however, only the sulfoxide appears to be formed. A plausible reaction sequence is discussed.
The reaction of representative alkoxysulfonium salts with a variety of alkoxides has been examined. The salts were found to undergo rapid alkoxy exchange followed by (a) base-catalyzed collapse to carbonyl compounds and sulfides or (b) α rearrangements (analogous to the Pummerer reaction) to produce monothioacetals. An ylide appears to be a common intermediate in these reactions. Appropriate deuterium-labeling experiments reveal that the elimination to carbonyl compounds proceeds via a cyclic transition state involving the sulfur ylide. The preponderance of the α-rearrangement reaction appears to be a function of the stability of the carbonium ion formed via elimination of alkoxide from the ylide intermediate. In all cases the ylide reacts rapidly in the manners stated and is not reprotonated to any significant extent.
t-Butyl hypochlorite reacts (2 moles) rapidly with diphenyl sulfide at room temperature to yield diphenyl sulfoxide and a mixture of products from the hypochlorite. The reaction is insensitive to light and air and does not induce chlorination of cyclohexane. A polar mechanism involving molecular chlorine and diphenylsulfur dichloride is suggested. Dimethyl sulfide is oxidized similarly to dimethyl sulfoxide, stabilized toward further oxidation as its HCl complex. Dimethyl sulfoxide alone, however, reacts rapidly with 3 moles of hypochlorite to give some derivative of trichloromethyl methyl sulfoxide, and more slowly with additional hypochlorite with C-S bond cleavage since CCl4 is one of the products formed. t-Butyl hypochlorite undergoes an acetate-catalyzed reaction with acetic anhydride, apparently to give acetyl hypochlorite and t-butyl acetate. The former then decomposes to methyl chloride and CO2. No evidence is found for the exchange of chlorine between t-butyl hypochlorite and acetic acid as proposed by Anbar and Dostrovsky. In fact, acetic acid inhibits the above anhydride exchange.
Para-substituted phenyl methyl sulfoxides-18O undergo oxygen-18 exchange with water in aqueous dioxane solutions of most mineral acids (reduction of the sulfoxides to sulfides takes place with hydrobromic and hydroiodic acids), but hydrochloric acid is a more effective catalyst by at least a factor of ten than other mineral acids at the same concentration. A much slower base-catalyzed exchange has also been detected. For the hydrogen chloride catalyzed exchange, the relative rates for p-methoxy-, p-methyl-, unsubstituted, p-chloro-, and p-nitro-phenyl methyl sulfoxides are 2.18, 1.61, 1.00, 0.52, and 0.21, respectively. A Hammett plot of log k/k0 vs. σ is linear with ρ = 1.046. Coupled with the work of others, these results indicate that there are at least four mechanisms for oxygen-18 exchange between sulfoxides and water.
The reaction of ClO- and BrO- with NO2- proceeds with almost complete transfer of hypohalite oxygen to nitrite. This reaction has been applied in the isotopic analysis of ClO- and BrO- undergoing exchange with water. The exchange of ClO- and water in alkaline solution proceeds by the paths kA[(ClO-)/(OH-)] and kB[[(ClO-)(Cl-)]/(OH-)]. Paths of similar kinetic form are indicated for the exchange of BrO- and water, and Cl- as well as Br- can catalyze the exchange. The reactions reverse to the kB paths are the attack of Cl2, Br2 or BrCl by OH-, and the specific rates for these reactions have been calculated. The mechanisms of the reactions and the mode of action of H+ in reactions of oxy-ions are discussed.
It has been shown that the proportions of cis and trans sulfoxides obtained by the oxidation of 4-substituted thianes vary over a wide range with change in the oxidizing agent. The mechanisms of certain of these oxidations are discussed with reference to steric approach control, product development control, and thermodynamic product control. It has been observed that dinitrogen tetroxide rapidly and cleanly equilibrates sulfoxides and that a six-membered ring sulfoxide is more stable with the oxide in the axial position.
The kinetics of the oxidation of thioxane (1-thia-4-oxacyclohexane) by hydrogen peroxide in several solvents (H2O, D2O, ethylene glycol, MeOH, i-PrOH, t-BuOH, acetic acid, dioxane, and N-methylacetamide) have been investigated. Some mixed solvent systems have been studied, as has the influence of solvent on the mechanistically related oxidation of thioxane by t-butyl hydroperoxide. The results are discussed in terms of solvent participation in the activated complex.
The rates of reaction of a number of nucleophiles with methyl iodide and trans-[Pt(py)2Cl2] have been measured in methyl alcohol at 25°. Relative nucleophilic reactivity parameters, nCH3I and nPt, have been calculated. It was not found possible to correlate these numbers with each other or with other extra-kinetic data. Equations in the literature for predicting nucleophilic reactivity have only a limited range of usefulness.
The hydrolysis of alkoxysulfonium salts, obtained by the O-alkylation of sulfoxides, proceeds with inversion of configuration of the sulfur atom. The method has been employed to interconvert (R)- and (S)-benzyl p-tolyl sulfoxide and the cis and trans sulfoxides derived from a series of 4-substituted thianes. Several methods were employed successfully to separate the geometrical isomers of the 4-substituted thiane 1-oxides. The mechanism of displacement reactions on sulfur is discussed.