Sodium Methanethiolate Research Articles

Synthesis of hydroxymethyl analogues of mannostatin A and their evaluation as inhibitors of GH38 α-mannosidases

Analogues of mannostatin A were synthesised and evaluated as inhibitors of GH38 α-mannosidases. Different regioselectivity of aziridine opening with sodium methanethiolate was observed and investigated by quantum mechanics calculations.

Efficacy of Intravenous Hydroxocobalamin for Treatment of Sodium Methanethiolate Exposure in a Swine Model (Sus scrofa) of Severe Methanethiol Toxicity.

Methanethiol is a highly toxic chemical present in crude oil and natural gas. At high concentrations, methanethiol causes metabolic acidosis, seizures, myocardial infarction, coma, and death. Occupational Health and Safety Administration lists methanethiol as a potential terrorist weapon. Methanethiol blocks the electron transport chain, resulting in lactic acidosis and acidemia. There is no specific treatment for methanethiol. Our objective was to measure the efficacy of intravenous (IV) hydroxocobalamin (HOC) versus no treatment (control) in methanethiol-induced apnea in a swine model. Sixteen anesthetized swine received IV sodium methanethiolate to apnea and were randomized to receive either IV HOC or no treatment. Physiologic and laboratory parameters were monitored throughout the study. Power analysis indicated that 8 animals per group would be sufficient to find a moderate effect (f = 0.24) with 2 groups, α = 0.05, and 80% power. Both groups were similar in baseline characteristics. Following treatment, the HOC group had significantly higher heart rate and blood pressure at 5-10minutes post-apnea, higher systemic vascular resistance at 5minutes post-apnea, higher tidal volume, higher end-tidal carbon dioxide, and lower end-tidal oxygen 10-15minutes post-apnea compared with controls. None of the animals survived to the end of the study (60minutes). The Kaplan-Meier survival curves were significantly different between cohorts (log-rank p = 0.0321), with the HOC group surviving longer than controls (32.4 ± 7.3 vs. 25.8 ± 1.0minutes). In our model of intravenous methanethiolate poisoning, IV HOC administration resulted in a transient improvement in vital signs and prolonged time to death; however, it did not improve survival.

γ-Ketosulfides and Hydroxysulfides from Sodium Methanthiolate of Sulfidic Spent Caustics

Condensation of pentan-3-one, hexan-2-one, 4-methylpentan-2-one, 5-methylhexan-3-one, or 2,6-dimethylheptan-4-one with formaldehyde and sodium methanethiolate, which is present in sulfidic spent caustic from the Orenburg gas processing plant, yields the corresponding mono- and bis[(methylsulfanyl)methyl]-substituted ketones or their mixtures depending on the reactant ketone structure. Alkylthiomethylation of butan-2-one with equimolar amounts of formaldehyde and sodium methanethiolate results in 3-methyl-5-thiahexan-2-one or, in the case of a twofold excess of the reagents, in 2-methyl-1,5-bis(methylsulfanyl)-4-[(methylsulfanyl)methyl]pentan-3-one. On the basis of 3-methyl-5-thiahexan-2-one, new polyfunctional [(methylsulfanyl)methyl]-substituted alcohol, α-hydroxymethylketone, 1,3-diol, and 1,3-dioxane have been obtained.

Synthesis and Evaluation of Novel 3‐Allylseleno‐6‐Alkylsulfonylpyridazine Derivatives with Potential Anticancer Properties

A new series of 3‐allylseleno‐6‐alkylsulfonylpyridazines and 3‐allylseleno‐6‐alkylsulfinylpyridazines were synthesized from 3,6‐dichloropyridazine for anticancer agent development. The inhibitory effects of 3‐allylseleno‐6‐alkylsulfonylpyridazines on human cancer cell lines were investigated. The synthesis involved thiolation, oxidation, selenylation, and Se‐allylation of alkylthiols. That is, sodium methanethiolate, ethanethiol, propanethiol, butanethiol, pentanethiol, and hexanethiol were inserted into the 6‐position of the pyridazine nucleus. These new synthetic compounds exhibited antiproliferative activity against human breast cancer (MCF‐7), hepatocarcinoma (Hep3B), and human colon carcinoma (RKO) cells in CCK‐8 assays, and are potential candidates for cancer chemotherapy.

Development of stable isotope dilution assays for the quantitation of the food odorants hydrogen sulphide, methanethiol, ethanethiol, and propane-1-thiol and application to durian (Durio zibethinus L.) pulp

Stable isotope dilution assays were developed for the quantitation of the highly volatile odorants hydrogen sulphide, methanethiol, ethanethiol, and propane-1-thiol using sodium (34S)sulphide, sodium (2H3)methanethiolate, (2H5)ethanethiol, and (2H7)propane-1-thiol as internal standards and 3-buten-2-one as derivatisation reagent. Applying sodium as the reducing agent, sodium (34S)sulphide was synthesised from 34S8 and sodium (2H3)methanethiolate from (2H6)dimethyl sulphide. The analytical approach included homogenisation of the food material with the added standards, derivatisation, solvent extraction, and solvent-assisted flavour evaporation (SAFE). Separate detection of analytes and standards was achieved by two-dimensional heart-cut gas chromatography–mass spectrometry using chemical ionisation and characteristic ions of the derivatives 4,4′-sulphanediyldi-2-butanone, 4-(methylsulphanyl)butan-2-one, 4-(ethylsulphanyl)butan-2-one, and 4-(propylsulphanyl)butan-2-one and their isotopically substituted analogues. Application of the approach to durian pulp resulted in high odour activity values (OAV = concentration/odour threshold) with ethanethiol (OAV 480000) being the most potent odorant, followed by methanethiol (OAV 45000), propane-1-thiol (OAV 6300), and hydrogen sulphide (OAV 330).

Crystal structure of 2,3,5,6-tetrakis[(methylsulfanyl)methyl]pyrazine

The title compound, C12H20N2S4, synthesized by the reaction of 2,3,5,6-tetra­kis­(bromo­meth­yl)pyrazine with sodium methane­thiol­ate, crystallizes with a half -mol­ecule in the asymmetric unit. The whole mol­ecule is generated by inversion symmetry; the inversion centre being located in the centre of the pyrazine ring. The mol­ecule has an S-shaped conformation with two (methyl­sulfan­yl)methyl substituent arms directed above the plane of the pyrazine ring and two below. The C(H3)—S—C(H2)—C(aromatic) torsion angles are 70.47 (18) and −67.65 (17)°, respectively. In the crystal, mol­ecules are linked via weak C—H⋯S hydrogen bonds, forming chains along [001] and enclosing R 2 2(12) ring motifs. The chains are linked by further weak C—H⋯S hydrogen bonds, forming sheets lying parallel to (101).

ChemInform Abstract: Regiocontrolled SNAr Reaction on 2,3‐Dihalopyridines with NaSMe to Obtain Bromo(methylthio)pyridines as Key Precursors of 3‐Halo‐2‐(hetero)arylthieno[2,3‐b]pyridines and Thieno[3,2‐b]pyridines.

The synthesis of 3-halo-2-(hetero)arylthieno[2,3-b]pyridines and 3-halo-2-(hetero)arylthieno[3,2-b]pyridines has been performed through a three-step methodology from 3-bromo-2-chloropyridine or 2-bromo-3-fluoropyridine, respectively. The key step of this methodology is the formation of the required bro­mo(methylthio)pyridines by a regiocontrolled nucleophilic aromatic substitution (SNAr) with sodium methanethiolate (NaSMe). Then, the Sonogashira coupling with (hetero)arylalkynes followed by a halocyclization with bromine or iodine, afforded the expected 3-halo-2-(hetero)arylthienopyridines.

Regiocontrolled SNAr Reaction on 2,3-Dihalopyridines with NaSMe To Obtain Bromo(methylthio)pyridines as Key Precursors of 3-Halo-2-(hetero)arylthieno[2,3-b]pyridines and Thieno[3,2-b]pyridines

The synthesis of 3-halo-2-(hetero)arylthieno[2,3-b]pyridines and 3-halo-2-(hetero)arylthieno[3,2-b]pyridines has been performed through a three-step methodology from 3-bromo-2-chloropyridine or 2-bromo-3-fluoropyridine, respectively. The key step of this methodology is the formation of the required bro­mo(methylthio)pyridines by a regiocontrolled nucleophilic aromatic substitution (SNAr) with sodium methanethiolate (NaSMe). Then, the Sonogashira coupling with (hetero)arylalkynes followed by a halocyclization with bromine or iodine, afforded the expected 3-halo-2-(hetero)arylthienopyridines.

A detailed quantum chemical study of the interactions of [Pt(dien)Cl]+ with a series of S-donor ligands: A computational approach

The mechanism of substitution reaction of [Pt(dien)Cl]+ (dien=diethylenetriamine) with a series of endogenous and exogenous S-containing ligands such as H2S, sodium methanethiolate (NaSMe), dimethylsulfane (Me2S), diethylsulfane (Et2S), thiourea (TU), 1,3-dimethylthiourea (DMTU), 1,3-diethylthiourea (DMTU), sodium-2-mercaptoethanesulfonate (mesna), sodium diethyldithiocarbamate (Naddtc), l-methionine (Met) and l-cysteine (Cys) were studied by computational methods. Within the framework of transition state theory, DFT-based calculations were performed in gas phase using the B3LYP exchange–correlation functionals as implemented in the Gaussian 09 program. Pentacoordinated square pyramidal (SP) and trigonal–bipyramidal (TBP)-like structure transition states (TS) along with other stationary points on potential energy surface were optimized and characterized. Results led us to conclude that for platination of S-ligands as protecting agents Naddtc, mesna and TU are more suitable than thiol and thioether ligands. Natural bond orbital (NBO) analysis method was performed for the investigation of major stabilizing orbital interactions. To obtain accurate energies for the reaction surfaces, single-point energies were calculated by conductor-like polarisable calculation model (CPCM) using larger basis sets at MP2 and B3LYP levels of theory. The sequence of rate constants found in our study in aqueous phase is: Naddtc>mesna>TU>Met>Cys>Me2S>Et2S≈MeSH>H2S≈DETU>NaSMe>DMTU.

From 2,3-, 2,6-, 3,4- and 4,6-Dichloroquinolines to Isomeric Chloroquinolinesulfonyl Chlorides

The action of sodium methanethiolate (in boiling DMF) on x,y-dichloroquinolines (1) (x=3 or 6, y=2 or 4) occured via chlorine ipso-substitution followed by methanethiolato-S-demethylation to yield x,y-quinolinedithiolates 2A which were: i) subjected to S-methylation, ii) oxidatively chlorinated to y-chloro-x-quinolinesulfonyl chlorides (5). Oxidative chlorination of y,y'-bis(x-chloro quinolinyl) disulfides (7) led to x-chloro-y-quinolinesulfonyl chlorides (8) accompanied by x,y-dichloroquinolines (1). Both quinolinesulfonyl chlorides 5 and 8 were efficiently converted to the corresponding quinolinesulfonamides 6 and 9.

Synthesis of thiamono- and thiabicyclanes from sodium sulfide and methanethiolate

1-[5-Acetyl-3-(methylthiomethyl)tetrahydro-3-thiopyranyl]-1-ethanone was obtained by the interaction of sodium sulfide and sodium methanethiolate with formaldehyde and acetone. The intramolecular crotonate condensation of the product leads to 4-methyl-1-methylthiomethyl-7-thiabicyclo[3.3.1]non-3-en-2-one. The participation of 3-methylthiomethyl-3-buten-2-one in the formation of a thiamono-cyclane is clarified. A probable scheme for the conversions is proposed.

Synthesis of 4- and 7-Quinolinesulfonamides from 4,7-Dichloroquinoline

Action of sodium methanethiolate (in boiling DMF) towards 4,7-dichloroquinoline (1) or 7-chloro-l-methyl-4(1H)-quinolinone (11) occured via chlorine ipso-substitution followed by methanethiolato-S-demethylation to yield dithiolate 1A or thiolate 18A, which were: i) subjected to S-methylation, ii) oxidatively chlorinated to quinolinesulfonyl chlorides (5 or 14 and 15). Oxidative chlorination of 4,4'-bis (7-chloroquinolinyl) disulfide (7) led to 7-chloro-4-quinolinesulfonyl chloride (8). All quinolinesulfonyl chlorides 5, 8, 14 and 15 were effectively converted to corresponding azinesulfonamides 6, 9, 16 and 17.

TLC Separation of Isomeric Diazinodithiins and Diazinyl Sulfides as the Smiles Rearrangement Products

The reactions of diazinodithiins 1, 5, and 9 with sodium methanethiolate in DMSO, followed by methylation with methyl iodide, proceed with or without the Smiles rearrangement to give isomeric diazinodithiins 4, 8, and 12 and diazinyl sulfides 2, 3, 6, 7, 10, and 11. The aim of this was to find TLC conditions to follow the rearrangement, to separate and identify thioazines 1–12. The retention parameter RF was measured and next calculated as separation factors ΔRF, RS, and α. The RF values were correlated with the dipole moments of thioazines 1–12 and the symmetry (C2h and C2v) of diazinodithiins 1, 4, 5, 8, 9, and 12.

From Haloquinolines and Halopyridines to Quinoline- and Pyridinesulfonyl Chlorides and Sulfonamides

The action of sodium methanethiolate (in boiling DMF) towards haloazines (i.e. chloro- or bromo-pyridines and quinolines) (1) (with halogen substituent in non-aza-activated position) causes sequentially halogen ipso-substitution to methylthioazines (2) and then S-demethylation to azinethiolates (3A), which were: i) subjected to S-methylation, ii) oxidized to diazinyl disulfides (4) and iii) oxidatively chlorinated to azinesulfonyl chlorides (5). α- and γ-pyridine- and quinolinesulfonyl chlorides (5a, 5c, 5d and 5f) were prepared by oxidative chlorination of respective disulfides (4) performed in conc. hydrochloric acid and characterized by 1 H and 13 C NMR spectra. All azinesulfonyl chlorides (5) were effectively converted to corresponding azinesulfonamides (6).

Functionalization of [60]fullerene through the anionic route

Abstract The reactivity of C602– anion, easily generated upon chemical reduction of the C60 core by sodium methanethiolate, has been systematically investigated versus a great number of saturated halogenated compounds RX or X–CH2–R′–CH2–X (X = I or Br), while these halo-compounds are unreactive with C60 itself. Various C60-derivatives in the series of bis-adducts R2C60 and fused cycloadducts R′(CH2)2C60 are thus obtained in fair to good yields, the R or R′ groups bearing functionalities such as ethylenic double bond, halogen, ketone, alcohol, or ester moieties. On the other hand a judicious utilization of the overall mechanism of the reaction between C602– anion and well chosen different RX and R′X compounds allow to extend this methodology to the preparation of mixed adducts RR′C60. Functional adducts in the series R2C60 and R′(CH2)2C60 are new attractive building blocks in C60 chemistry, and can lead to novel highly functionalized C60-based molecules. Some examples of such covalent ensembles are presented, the specific physical properties of which are typical of organic materials. To cite this article: J. Cousseau et al., C. R. Chimie 9 (2006).

Synthesis and Structure of Dipyrido-1,4-dithiins

Synthesis, properties and reactions of two isomeric dipyrido-1,4-dithiins of the C-2h and C-2v symmetry are described. Their structure detennination and identification are based on spectroscopic methods (H-1 and C-13 NMR, HETCOR, gHMBC and MS), physical properties (mp and R-f), the 1,4-dithiin ring opening reactions and finally X-Ray analysis. A very unusual type of the Smiles rearrangement (S -> S, the pyridyl group migrates from one sulfur atom to another) during the 1,4-dithiin ring opening with sodium methanethiolate enabling isomerization of dithiin with the C-2h symmetry to dithiin with the C-2v symmetry is found.

A New Approach to Imidazo[1,5-a]indole Derivatives

Reaction of indole-2-carbonyl isothiocyanate (1) with sodium methanethiolate afforded 1-thioxo-1H-imidazo[1,5-a]indol-3(2H)-one (3). Its methylation with methyl iodide in the presence of lithium hydride in dimethylformamide, or potassium carbonate in acetone resulted in the formation of corresponding S- and N-methyl derivatives 4 and 5. N-(Indole-2-carbonyl)thiocarbamates and N-(indole-2-carbonyl)thioureas prepared by treatment of isothiocyanate 1 with corresponding nucleophilic reagents were S-methylated with methyl iodide in acetone in the presence of potassium carbonate. The obtained N-(indole- 2-carbonyl) substituted thiocarbonimidates 15, 16 and isothioureas 17-20 afforded by treatment with lithium hydride in dimethylformamide the derivatives of imidazo[1,5-a]- indol-3-one 23-28 in 49-87% yields. Antifungal activity of the prepared compounds has been examined, using the fungus Bipolaris leersiae. 1-Methylsulfanyl-3H-imidazo-[1,5-a]- indol-3-one (4) exhibited the highest antifungal activity.

Syntheses and properties of oxyalkylene copolymers containing methylsulfonylmethyl and chloromethyl side groups or methylthiomethyl and chloromethyl side groups

Three series of oxyalkylene copolymers containing chloromethyl and methylthiomethyl side groups were synthesized by reacting the starting chloromethyl polymers with sodium methanethiolate. The methylthiomethyl groups were oxidized to sulfone groups using m-CPBA to produce oxyalkylene copolymers containing chloromethyl and methylsulfonylmethyl side groups. T g versus composition for methylthiomethyl-substituted copolymers followed those calculated from the Fox equation, while 2 of the 3 series of methylsulfonylmethyl-substituted copolymers showed positive deviations from the Fox equation. T g s of the copolymers calculated using the Johnston equation showed very good agreement with experimental values in all cases.

Regio- and Diastereoselectivity in the Thiomethylation of α-(1-Hydroxyalkyl)acrylate Derivatives

The regio-and diastereoselectivity of reactions of selected α-(1-hydroxyalkyl)acrylate derivatives with sodium methanethiolate have been investigated. The hydroxy compounds typically undergo conjugate addition with up to 66% d.e., while the acetoxy and bromo analogues favour SN' and SN reactions, respectively.

Synthesis and Structure of a Cyclic Complex of Digold Sulfide Au2S and of Related Compounds

Abstract1,4‐Bis(diphenylphosphanylmethyl)benzene (1) was converted into its bis[chlorogold(I)] complex [1 · (AuCl)2] upon treatment with two equivalents of chloro(dimethyl sulfide)‐gold(I). The reaction of 1 · (AuCl)2 with one equivalent of silver tetrafluoroborate afforded a cyclic di[gold(I)]chloronium tetrafluoroborate [1 · Au2Cl+ BF‐4]. Substitution of chloride in 1 · (AuCl)2 by sodium methanethiolate in wet chloroform, gave the bis[methylthiogold(I)] complex 1 · (AuSMe)2], while with sodium sulfide a cyclic complex 1 · Au2S was obtained. Reaction of 1 · (AuCl)2 with two equivalents of AgBF4 followed by treatment with diphenyldisulfide or sodium methanethiolate yielded the cyclic methyl/phenylsulfonium tetrafluoroborates 1 · Au2SPh+ BF‐4 and 1 · Au2SMe+BF‐4, respectively. All compounds were identified on the basis of their analytical and spectroscopic data. The crystal structures of 1 · (AuCl)2, 1 · (AuSMe)2, and 1 · Au2S have been determined. The Au2S complex has a cyclic structure with a narrow Au‐S‐Au angle of 86.7(1)° indicating a significant intraannular Au…Au interaction.