Thioacetic Acid Research Articles

Effect of S Replacement on the Mechanism of Unimolecular Reactions for Ground‐state Thioacetic Acid: A Theoretical Study

AbstractThe potential energy surfaces of nine molecular reactions for the ground‐state CH3C(O)SH and CH3C(S)OH have been investigated with a B3LYP method in conjugation with 6‐31G∗︁∗︁, cc‐pVDZ, aug‐cc‐pVDZ, and cc‐pVTZ basis sets. The present calculations predict that thioacetic acid mainly exists as a CH3C(O)SH tautomer, and both tautomers predominately adopt syn conformations, which reproduces the experimental observations. By comparison of the reactivity difference among CH3C(O)SH, CH3C(S)OH, and CH3C(O)OH, it can be concluded that the replacement of atom O by S in –OH group of CH3C(O)OH has a big effect on the molecular decompositions only when –SH takes part in the reaction as one group, while the CO or CS group has minor contribution to the reactivity difference.

A Simple and Efficient Preparation of Novel Formaldehyde Derivatives

New formaldehyde derivatives were prepared in good yields by a short and versatile route. Several crystal structures of corresponding thioacetic acid esters and thiols were determined. The thioacetates were cleaved under acidic or basic conditions affording the thiols in high yield, thus introducing the new substance classes of N-mercaptomethyl-alkylcarboxamides, N-mercapto­methylsulfonamides, and alkoxymethanethiols.

SAMs on Gold Derived from the Direct Adsorption of Alkanethioacetates Are Inferior to Those Derived from the Direct Adsorption of Alkanethiols

Self-assembled monolayers (SAMs) on gold derived from the direct adsorption of thioacetic acid S-decyl ester (C10SAc) and thioacetic acid S-octadecyl ester (C18SAc) were compared to the corresponding SAMs derived from the analogous adsorption n-decanethiol (C10SH) and n-octadecanethiol (C18SH). All SAMs were characterized using ellipsometry, contact angle goniometry, polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS), and X-ray photoelectron spectroscopy (XPS). The comparison revealed that the SAMs generated from the thioacetates are not as densely packed and well ordered as the SAMs generated from the thiols. Furthermore, studies of the kinetics of adsorption found that the thioacetates adsorb more slowly than the corresponding thiols.

Synthesis, Characterization and Reactivity of a Diorganotin Thiocarboxylate: Dimethyl(thioacetato)-tin(IV) Chloride and its Reactions with Nucleophiles Exhibiting Desulfurization

Dimethyl(thioacetato)tin chloride (1) was synthesized by the reaction of dimethyltin dichloride with thioacetic acid in the presence of triethylamine. Compound 1 was subjected to hydrolysis under different reaction conditions in order to obtain sulfido/hydrosulfidotin compounds. Except for one case where the product was hexamethyl-1,3,5-trithia-2,4,6-tristannacyclohexane, (Me2SnS)3 (4), all other reactions led to desulfurization, and the products obtained were organostannoxane compounds, dinuclear tetramethyl-oxo-dichloroditin, {Me2SnCl2.Me2SnO} 2 (2), and tetraacetatodioxotetra( dimethyltin), (Me2Sn)4O2(O2CMe)4 (3). These complexes have been characterized by 1H, 13C, 119Sn NMR and FTIR spectroscopy, and compounds 2 - 4 also by X-ray crystallography. Density functional calculations were performed to explain the structure and reactivity of the compounds.

Selective Benzylic and Allylic Alkylation of Protic Nucleophiles with Sulfonamides through Double Lewis Acid Catalyzed Cleavage of sp3 Carbon–Nitrogen Bonds

The acid-catalyzed benzylic and allylic alkylation of protic nucleophiles is fundamentally important for the formation of carbon-carbon and carbon-heteroatom bonds, and it is a formidable challenge for benzylic and allylic amine derivatives to be used as the alkylating agents. Herein we report a highly efficient benzylic and allylic alkylation of protic carbon and sulfur nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp(3) carbon-nitrogen bonds at room temperature. In the presence of a catalytic amount of inexpensive ZnCl(2)-TMSCl (TMSCl: chlorotrimethylsilane), 1,3-diketones, beta-keto esters, beta-keto amides, malononitrile, aromatic compounds, thiols, and thioacetic acid can couple with a broad range of tosyl-activated benzylic and allylic amines to give diversely functionalized products in good to excellent yields and with high regioselectivity. Furthermore, the cross-coupling reaction of 1,3-dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one-step synthesis of polysubstituted furans and benzofurans.

Study on Disulfur-Backboned Nucleic Acids: Part 3. Efficient Synthesis of 3′,5′-Dithio-2′-Deoxyuridine and Deoxycytidine

A general method is described for synthesizing 3′,5′-dithio-2′-deoxypyrimidine nucleosides 6 and 13 from normal 2′-deoxynucleosides. 2,3′-Anhydronucleosides 2 and 9 are applied as intermediates in the process to reverse the conformation of 3′-position on sugar rings. The intramolecular rings of 2,3′-anhydrothymidine and uridine are opened by thioacetic acid directly to produce 3′-S-acetyl-3′-thio-2′-deoxynucleosides 3 or 5. To cytidine, OH− ion exchange resin was used to open the ring and 2′-deoxycytidine 10 was abtained in which 3′-OH group is in threo-conformation. The 3′-OH is activated by MsCl, and then substituted by potassium thioacetate to form the S,S′-diacetyl-3′,5′-dithio-2′-deoxycytidine 12. The acetyl groups in 3′,5′ position are removed rapidly by EtSNa in EtSH solution to afford the target molecules 6 and 13. The differences of synthetic routes between uridine and cytidine are also discusssed.

Chemical Manipulation by X-rays of Functionalized Thiolate Self-Assembled Monolayers on Au

The chemical modification caused by prolonged exposure to X-rays on a series of para-substituted phenyl moieties (-NO2, -CN, -CHO, -COOH, -CO2Me, and -CO2(1)Bu) at the surface of thiolate-Au self-assembled monolayers (SAMs) has been investigated by X-ray photoelectron spectroscopy (XPS). Furthermore, the influence that the phenyl group has on the chemical modification induced by the X-ray irradiation on the SAMs was investigated by comparing the XPS results obtained from irradiation on a NO2-aromatic-terminated SAM (6-(4-nitro-phenoxy)-hexane-1-thiolate (NPHT)) and NO2-aliphatic-terminated SAM (thioacetic acid S-(12-nitrododecyl) ester (TNDDE)). The NPHT and TNDDE SAMs have been shown to behave differently to X-ray exposure. The irradiation of the NPHT SAM led to the reduction of the nitro (-NO2) moiety to the amine (-NH2) moiety, as shown by the decrease in the intensity of the N 1s photoelectron peak for -NO2 (406 eV) in the XPS spectra with the concomitant increase in the N 1s photoelectron peak for -NH2 (399 eV). On the TNDDE SAM, XPS showed the -NO2 photoelectron peak again decreasing with prolonged X-ray irradiation whereas no peak was observed at 399 eV; therefore, the -NO2 moieties are selectively cleaved. No change was observed on the other functionalized monolayers apart from the -CO2(t)Bu-functionalized monolayer, where after 100 min of X-ray irradiation approximately 11% of the carbon content was lost. The S 2p and O 1s spectra remained unchanged during the irradiation suggesting the conversion of the -CO2(t)Bu to the -COOH moiety, although the conversion was not complete because the tertiary butyl moiety contributes 25% to the total carbon content of the SAM. Also, there was no evidence of the molecules desorbing from the substrate for any of the SAMs studied during the X-ray irradiation as shown by no change in the S 2p and C 1s XPS spectra taken during the X-ray irradiation.

Mechanistic Studies on the Nucleation of Zinc Sulphide Nanoparticles by Means of XAFS Spectroscopy

Mechanistic studies on the nucleation of zinc sulphide nanoparticles from thioacetic acid were performed by means of X-ray absorption fine structure spectroscopy. Solutions of thioacetic acid and zinc salt (acetate or oxide) dissolved in a solvent (acetic acid or acetone) were investigated and compared with the corresponding zinc precursor and crystalline zinc sulphide to study the evolution of the structural environment around the zinc atoms in the solution. The investigations reveal that the coordination of sulphur atoms take place immediately when the mixture is prepared and zinc-sulphur species gradually evolve during the course of the reaction. However, the complete formation of zinc sulphide could not be evidenced even after a considerable period of time. This is likely due to the presence of unreacted zinc-oxygen species. The obtained results indicate that, once dissolved, zinc oxide reacts comparatively faster with thioacetic acid than with zinc acetate and that the choice of the reaction medium plays a crucial role in determining the kinetics and mechanism of zinc sulphide nucleation.

Activation of TRPA1 by Farnesyl Thiosalicylic Acid

The nonselective cation channel TRPA1 (ANKTM1, p120) is a potential mediator of pain, and selective pharmacological modulation of this channel may be analgesic. Although several TRPA1 activators exist, these tend to be either reactive or of low potency and/or selectivity. The aim of the present study, therefore, was to identify novel TRPA1 agonists. Using a combination of calcium fluorescent assays and whole-cell electrophysiology, we discovered several compounds that possess potent, selective TRPA1-activating activity, including several lipid compounds (farnesyl thiosalicylic acid, farnesyl thioacetic acid, 15-deoxy-Delta(12,14)-prostaglandin J(2), and 5,8,11,14-eicosatetraynoic acid), and two marketed drugs: disulfiram (Antabuse; a compound used in the treatment of alcohol abuse) and the antifungal agent chlordantoin. Farnesyl thiosalicylic acid activates the channel in excised patches and in the absence of calcium. Furthermore, using a quadruple TRPA1 mutant, we show that the mechanism of action of farnesyl thiosalicylic acid differs from that of the reactive electrophilic reagent allylisothiocyanate. As a TRPA1 agonist with a potentially novel mechanism of action, farnesyl thiosalicylic acid may be useful in the study of TRPA1 channels.

Synthesis and Reactivity of 4‐(2‐Chloro‐5‐nitrophenyl)‐1,2,3‐thiadiazole. A Novel One‐Pot Synthesis of N‐Substituted Indole‐2‐thiols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Ring-opening of oxazolines derived from l-serine: a short and efficient stereoselective synthesis of all four diastereomers of 3-mercaptoaspartic acid derivatives

Facile methods are described for accessing four diastereomerically pure 3-mercaptoaspartic acid derivative from l-aspartic acid. In our synthesis, ring-opening reactions of oxazoline-4,5-dicarboxylate with thiolacetic acid as well as the stereochemical interconversion of both α- and β-configuration via oxazoline chemistry were utilized as key steps.

Synthesis and Reactivity of 4-(2-Chloro-5-nitrophenyl)-1,2,3-thiadiazole. A Novel One-pot Synthesis of N-Substituted Indole-2-thiols

4-(2-Chloro-5-nitrophenyl)-1,2,3-thiadiazole undergoes ring opening to produce a thioketene intermediate that reacts with an O- or N-nucleophile, forming an ester or an amide of the aryl-substituted thioacetic acid. Intermolecular cyclization of the thioacetic acid derivative via nucleophilic substitution of halogen in the aromatic ring gives an N-substituted indole-2-thiol (in case of an N-nucleophile) or a 2-alkoxy-substituted benzo[b]thiophene (in case of an O-nucleophile). The reaction is also applicable to the synthesis of heterocyclic analogues of N-substituted indole-2-thiols: 1-butyl-1,3-dihydropyrrolo[2,3-b]pyridine-2-thione was synthesized as an example. In the presence of potassium thioacetate (an S-nucleophile) 4-nitro-2-(1,2,3-thiadiazol-4-yl)benzenethiol is formed more quickly than thiadiazole ring opening occurs, making the heterocyclic ring tolerant toward the base.

Cadmium Sulfide Nanoparticle Synthesis in Dps Protein from Listeria innocua

Cadmium sulfide (CdS) nanoparticles (NPs) were synthesized in the cavity of the recombinant Dps cage-shaped protein from Listeria innocua (rLiDps) modifying the slow chemical reaction synthesis (SCRY) and two-step synthesis protocol (TSSP). The SCRY is realized by stabilizing cadmium ions as tetraamminecadmium and employing thioacetic acid (which is added in the final stage of the TSSP). The optimized condition produced cubic CdS NPs in the rLiDps cavity with an average diameter of 4.2 nm and small size dispersion. These CdS NPs showed photoluminescence. It was also found that the pH of the reaction solution affects the elemental composition CdS NPs. At pH 4.5 and 6.5, CdxSy (x < y) NPs were obtained, and at pH 8.5, cubic CdS NPs were synthesized at pH 8.5.

Synthesis and Pharmacological Study of Thiazolidinones and Mannich Bases of 4‐Amino‐3‐mercapto‐5‐pyridin‐3′‐yl‐[1,2,4]‐triazole.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Efficient Synthesis of Taurine and Structurally Diverse Substituted Taurines from Aziridines

Taurine and substituted taurines were synthesized efficiently from aziridines via ring-opening reaction with thioacetic acid, oxidation with performic acid, and hydrolysis in hydrochloric acid. The current method shows more benefit in purification and efficiency in the preparation of taurine and structurally diverse 2-substituted, 2,2-disubstituted, and 1,2-, 2,2-, and 2,N-alkylene taurines.

Fabrication of CdS nanoparticles in the bio-template, apoferritin cavity by a slow chemical reaction system

Cadmium sulfide (CdS) nanoparticle (NP) was synthesized in the apoferritin cavity by slow chemical reaction system (SCRY) and two step synthesis protocol (TSSP). The survey showed thioacetic acid as the optimum sulfur source to form CdS NPs in the apoferirin cavity. Thioacetic acid degrades slowly in weak acidic solution and releases the sulfide ions continuously for long period. The synthesized NP was determined as CdS in cubic phase by energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction measurement (XRD). Semiconductor CdS NP surrounded by protein shell can disperse in aqueous solution and will be able to be applied to nano-electronic devices or fluorescent biomarker.

Gas-phase acidities of thiocarboxylic acids

The gas-phase acidity of thioacetic acid, determined using ion–molecule equilibrium reactions, was found to be Δ G acid = 329.0 ± 1.5 kcal mol −1. The gas-phase acidity of thiobenzoic acid was determined by ion–molecule bracketting reactions to be Δ G acid = 323 ± 5 kcal mol −1. Gas-phase acidities of these compounds, as well as of thioformic acid, were calculated; our calculations and experiments are in good agreement. The calculated value of the enthalpy of deprotonation of thioformic acid is consistent with previously published computational results.

A Microwave and Quantum Chemical Study of (Trifluoromethyl)thiolacetic Acid, CF3COSH, a Compound with an Unusual Double-Minimum Potential

The microwave spectra of CF3COSH and one deuterated species, CF3COSD, have been investigated by Stark spectroscopy in the 40-80 GHz spectral range at -78 degrees C and by quantum chemical calculations using the HF, MP2, and B3LYP procedures with the aug-cc-pVTZ basis set. The microwave spectrum of one conformer was assigned. The conformations of the COSH and CF3 groups determine the overall conformation of this rotamer. It was not possible experimentally to find precise values for the associated dihedral angles, but it appears that the COSH group is distorted somewhat from an exact synperiplanar arrangement, while the CF3 group is rotated several degrees from a position where one of the C-F bonds eclipses the C-S bond. This rotamer tunnels through a transition state that has an exact Cs symmetry, where one C-F bond eclipses the C-S bond and the COSH group is synperiplanar. Relative intensity measurements yielded 28(15) cm-1 for the tunneling frequency. Two additional vibrationally excited states were assigned and their frequencies determined to be 94(30) and 184(40) cm-1, respectively. The theoretical calculations predict conflicting conformational properties for the identified rotamer. The B3LYP calculations find an exact synperiplanar arrangement for the COSH group, whereas the MP2 and HF calculations predict that this group is distorted slightly form this conformation. One of the C-F bonds is found to eclipse the C-S bond in the B3LYP calculations, while the MP2 calculations predict a slight deviation and the HF calculations a large deviation from the eclipsed position, as the corresponding F-C-C-S dihedral angle is calculated to be 0.9 degrees (MP2) and 27.6 degrees (HF). All three methods of calculations predict that a second rotamer coexists with the identified form but is several kJ/mol less stable. The spectrum of this form, which has overall Cs symmetry and is predicted to have an antiperiplanar conformation for the COSH group with one of the C-F bonds eclipsing the C=O bond, was not identified.

Lactotriaose-containing carbosilane dendrimers: Syntheses and lectin-binding activities

Carbosilane dendrimers periphery-functionalized with lactotriaose (GlcNAcβ1–3Galβ1–4Glc) with valencies of three, four, six, and twelve were prepared for use in a lectin-binding assay. A lactotriaose derivative was prepared from d-glucosamine and d-lactose derivatives. The N-Troc-protected glucosamine glycosyl donor and 3′-O-unprotected lactose glycosyl acceptor were condensed in the presence of silver trifluoromethanesulfonate and methylsulfenyl bromide to provide corresponding trisaccharide with new β-1-3 linkages in 92% yield. The protection group of the trisaccharide was transformed into an acetyl group. The 4-pentenyl glycoside was prepared from the acetate via glycosyl bromide. The alkene was converted into acetyl sulfide by addition of thioacetic acid under radical conditions. The lactotriaose unit was linked with carbosilane dendrimers to afford acetyl-protected glycodendrimers. De-O-acetylation of the dendrimers was carried out in the presence of sodium methoxide and then aq NaOH to give the desired lactotriaose clusters using a carbosilane dendrimer backbone. Their biological activities toward WGA were evaluated by fluorescence methods. The binding constants of free lactotriaose and trivalent, tetravalent, hexavalent, and dodecavalent glycodendrimers to WGA were determined to be 1.1 × 10 3, 4.4 × 10 4, 5.1 × 10 4, 2.8 × 10 6, and 1.3 × 10 6 M −1, respectively. The hexavalent glycodendrimer showed a 2500-fold larger binding effect than that of free lactotriaose.

Synthesis of Symmetric Diallyl Disulfides from Baylis-Hillman Acetates

During the past decade, the Baylis-Hillman (BH) reaction has been extensively studied and is now one of the most efficient carbon-carbon bond forming reaction. Much attention has recently been focused on the SN2' nucleophilic substitution of the BH adducts with a variety of nucleophiles and many heterocycles have been synthesizied including quinolines, dihydroquinolines, quinolones, pyrrolidines, coumarins and indoles. It was reported that 2,2'-dithiodibenzaldehyde could be used as a masked thiosalicyl aldehyde in the BH reaction with suitably activated alkenes in the presence of DBU to give thiochromenes. However, the most obvious drawback is that the starting dithiodibenzaldehyde is not available commercially. As part of our continuing studies towards development of the BH chemistry, we desired to have the thiol group at the allylic position of 3-aryl-2-propenoates. To the best of our knowledge, there are only limited number of reports in the literature for the conversion of the BH adducts into the corresponding 2-acetylthiomethyl-2-propenoates in acidic conditions using thiolacetic acid, but the thiolacetylation of the BH acetates is not known. In principle, such acetylthiomethyl compounds after hydrolysis of thiolester group might be extended further toward the building of thiochromene derivatives via an intramolecular nucleophilic aromatic substitution reaction as shown in Scheme 1. The readily available BH acetates 1a-h provided a convenient starting point for the synthesis of 2-acetylthiomethyl-2-propenoates 2a-h. Treatment of the BH acetates 1a-h with thiolacetic acid in the presence of triethylamine at room temperature gave the 2-acetylthiomethyl-2-propenoates 2a-h in good to excellent yields as shown in Table 1 (Scheme 2). The stereochemistry of the products was established by compairing H NMR values of olefinic proton with literature values of similar compounds. In all cases, the stereoselectivity was found to be 100% (E)-selectivity. In order to prepare the unknown thiol derivative 3, we carried out the hydrolysis of thioacetyl derivative 2a with weakly basic NaN3 in aqueous acetone 13 at reflux temperature. The desired allyl thiol 3a was not obtained. Instead, symmetric diallyl disufides 4a produced in 71% yield. This result led us to transform the representative acetylthiomethyl derivatives 2b-h into diallyl disufides 4b-h under the similar reaction conditions. We then examined the effect of the base. In the case of using NaOMe in methanol the same reaction occurred rapidly, but the yields of disulfides are generally low. The results and reaction conditions were summarized in Table 2. The interconversion of thiols and disulfides is a fundamental transformation in organosulfur chemistry and such switching plays important role in biological system. The easy oxidation of thiols on exposure to air is well known. It is also known that autooxidation of thiols is accelerated by bases. Literatures reveal the availability of a Scheme 1 Scheme 2