Thioacetic Acid Research Articles

Synthesis of a useful anomeric thioacetate of an N-acetyllactosamine derivative and its application

A novel anomeric β-thioacetate of an N-acetyllactosamine derivative was efficiently synthesized in high yield from the known 2-azido glycosyl chloride using thioacetic acid as a convenient reagent. The synthesis involved not only an S N2 replacement of the chloride by a carbothiolate anion but also a reductive acetamidation of the azide group. Applications of the thioacetate for glycosidation were demonstrated to provide both O- and S-glycosides in high yields. Furthermore, both intermediates gave a new class of glycoclusters that included thioglycosidic linkages.

A Practical Procedure for the Synthesis of Esonarimod, (R,S)‐2‐Acetylthiomethyl‐4‐(4‐methylphenyl)‐4‐oxobutanoic Acid, an Antirheumatic Agent. Part 1.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Practical Procedure for the Synthesis of Esonarimod, (R,S)-2-Acetylthiomethyl-4- (4-methylphenyl)-4-oxobutanoic Acid, an Antirheumatic Agent. II#

An efficient large-scale synthesis of Esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (1), a new antirheumatic drug, was established. A small amount of water increased the yield of the Michael addition of thioacetic acid (4) to 2-methylene-4-(4-methylphenyl)-4-oxobutanoic acid (2) to give 1. Multikilogram amounts of 1 (over 25 kg) were successfully obtained using this procedure. In addition, this procedure was repeated nine times, and reproducible results were obtained. See Ref. [1]

The tert -Butyl Moiety—A Base Resistent Thiol Protecting Group Smoothly Replaced by the Labile Acetyl Moiety

Aryl t-butyl sulfides underwent quantitative tert-butyl/acetyl exchange reactions affording thioacetic acid S-aryl esters when treated with acetyl chloride and boron tribromide.

Molecular rectification: asymmetric current–voltage curves from self-assembled monolayers of a donor–(π-bridge)–acceptor dye

Thioacetic acid S-(10-{4-[2-cyano-2-(4-dicyanomethylenecyclohexa-2,5-dienylidene)ethylidene]-4H-quinolin-1-yl}decyl) ester (1a) forms self-assembled monolayers on gold with loss of the acetyl group, the thickness and contact area being 2.25 ± 0.05 nm and 0.36 ± 0.03 nm2 molecule−1 respectively. The films exhibit asymmetric current–voltage characteristics, which have been unambiguously assigned to molecular rectification.

Facile Synthesis of Thiolacetates from Trichloromethyl Compounds

A new method for the conversion of trichloromethyl compounds into the corresponding thiolacetates by treatment with sodium thiolacetate in the presence of thiolacetic acid is described. This transformation proceeds at room temperature in high yield when a strong electron-withdrawing substituent is attached to the trichloromethyl group.

Addition of thiols to ethyl 4,4,4-trifluorocrotonate

Ethyl 4,4,4-trifluorocrotonate 1 readily adds aliphatic and aromatic thiols and aminothiols at the double bond in the presence of catalytic amounts of alkylamines and ammonia to give 3-thiolation products. Thiolacetic acid reacts with ester 1 in the absence of a catalyst at 100 °C.

Synthesis of (Aminoiminomethyl)thioacetic Acid and Some of Its Esters.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Angiotensin II increases expression of cyclooxygenase-2: implications for the function of vascular smooth muscle cells.

In vascular smooth muscle, increased expression of cyclooxygenase-2 (COX-2) has emerged as an important mechanism for regulation of prostanoid synthesis influenced by vessel injury, cytokines, and growth factors. We have investigated how COX-2 participates in angiotensin II (ANG II)-mediated cell responses in cultured human vascular smooth muscle cells (VSMCs). ANG II type 1 (AT1) receptors induce increased accumulation of COX-2, both at the mRNA and protein levels. ANG II increased transcription of the COX-2 gene; also, nuclear extracts from stimulated cells had increased NF-kappa B binding to its DNA consensus sequence. ANG II-induced COX-2 expression was markedly blunted by inhibition of mitogen-activated protein kinase. Furthermore, the ANG II-induced increase in COX-2 protein abundance was attenuated by both the peroxisome proliferator-activated receptor alpha (PPARalpha) activator Wy-14,643 [pyrinixic acid; 4-chloro-6-(2,3-xylidino)-2-pyrimidinyl) thioacetic acid] and the PPARgamma activator 15d-PGJ2 (15-deoxy-Delta(12-14)-prostaglandin J2). Not only did ANG II increase COX-2 expression and prostaglandin synthesis, ANG II-stimulated DNA synthesis and cell migration were dependent on COX-2 activity. PPARalpha and PPARgamma activators inhibited ANG II-stimulated DNA synthesis and cell migration. These results suggest that ANG II enhances COX-2 expression at the transcription level; also, COX-2 activity plays an important role in mediating ANG II- induced proliferation and migration of VSMCs, suggesting the possibility of magnification of ANG II effects over time due to the induction of COX-2 expression. These results also demonstrate that both the alpha and gamma type of PPAR activators inhibit COX-2 expression induced by angiotensin II in VSMCs which may have therapeutic significance in vascular diseases.

Activated polyurethane modified with latent thiol groups

A novel type of modified polyurethane with pendant acetylthio groups (as a latent form of thiol groups) has been proposed for the use in surface modifications with various biomolecules. The polymer was prepared via a modified variant of low-temperature bromoalkylation of urethane hard segments followed by the reaction of pendant bromoalkyl groups with thiolacetic acid in mild conditions. The extent of modification with acetylthio groups can be made as high as 0.45 mmol/g. After deprotection of acetylthio groups and reaction of the resulting thiol groups with an excess of Ellman's reagent, 0.1 nmol/cm 2 of thiol-reactive 3-carboxy-4-nitrophenyldithio groups were detected on the surface of films cast from the modified polymer. A sensitive fluorescent probe—dansyl- l-cysteine was used for the quantification of thiol-reactive groups bound to the surface. The acetylthio-modified polyurethane is sufficiently stable to withstand conditions typical for the high-temperature processing (molding, extrusion) of polyurethanes.

Matrix Photochemistry of CH3C(O)SX Molecules with X = H, CH3, and C(O)CH3: Formation of Ketene in Another Decomposition Channel of Sulfenyl Carbonyl Compounds

CH 3 C(O)SC(O)CH 3 isolated in solid Ar, N 2 , or 5% CO-doped Ar at 15 K and CH 3 C(O)SH and CH 3 C(O)-SCH 3 isolated in solid Ar at 15 K were irradiated with broad-band UV-visible light (200 ≤ λ ≤ 800 nm). On the basis of the IR spectra of the matrixes, hydrogen abstraction from the CH 3 group to give ketene, H 2 C=C=O, with the elimination of HX [X = SC(O)CH 3 , SH, or SCH 3 ] was identified in each case as the main channel of photodecomposition within the confines of a solid matrix environment. The presence of a CH 3 ligand attached to the carbonyl function thus introduces a third type of elimination reaction for matrix-isolated sulfenyl carbonyl compounds of the general type XC(O)SY. Additionally, the conformational properties of the CH 3 C(O)SX molecules have been investigated. In the case of thioacetic acid (X = H), the matrix experiments indicate that the vapor at ambient temperatures consists of a mixture of the syn and anti forms, with the syn form predominating (ca. 85%). Broad-band UV-visible irradiation then results in interconversion of the conformers prior to decomposition. The identification of the different molecules has been underpinned by the results of ab initio and density functional theory (DFT) calculations.

Highly sulfurated heterocycles via dithiiranes and trithietanes as key intermediates.

2,2,4,4-Tetramethyl-3-thioxocyclobutanone (8b) easily reacts with gaseous chlorine to yield the stable alpha-chloro sulfenyl chloride 10. The same product was obtained when 8b was treated either with phosphorus pentachloride (PCl(5)) or sulfuryl chloride (SO(2)Cl(2)) in CCl(4) solution. Sulfur dichloride (SCl(2)) reacts with 8b to give the alpha-chloro thiosulfenyl chloride 12 along with an almost equimolar amount of the trisulfide 13b. The less reactive disulfur dichloride (S(2)Cl(2)) was shown to react slowly with 8b and the symmetrical tetrasulfide 15 was found as the exclusive product. The pure thiosulfenyl chloride 12 added to adamantanethione (8c) yielded the unsymmetrical trisulfide 13c. When 12 was treated with thioacetic acid, the acetylated trisulfide 17 was formed in high yield. "Unzipping" reactions with the acetylated disulfide 16 and trisulfide 17 with morpholine in THF at -40 degrees C led to the formation of mixtures of two sulfur-rich heterocycles identified as the pentathiepane 6b and the hexathiepane 7b. A mixture of analogous products was obtained when alpha-chloro sulfenyl chloride 10 was treated with sodium sulfide in anhydrous THF at -40 degrees C. The formation of 6b and 7b is believed to occur via the intermediate dithiirane 1b and/or the isomeric thiosulfine 2b. In the case of 17 the reaction starts probably with the formation of a nonisolable tetrathiane 18b as presented in Scheme 5.

Preparation of β-amino-α-mercapto acids and amides: stereocontrolled syntheses of 2′-sulfur analogues of the taxol C-13 side chain, both syn and antiS-acetyl- N-benzoyl-3-phenylisocysteine

Stereoselective syntheses of both syn and anti S-acetyl- N-benzoyl-3-phenylisocysteine as coupling-ready reagents via the ring-opening reactions of trans- and cis-oxazoline-5-carboxylates with thiolacetic acid were demonstrated. In addition, we report upon ring-opening reactions of oxazoline-5-carboxamides. Ab initio molecular calculations were used to explain the different reactivities of these oxazolines with respect to the ring-opening reaction.

A practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, an antirheumatic agent (part 1).

An efficient and practical procedure for the synthesis of esonarimod, (R,S)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (1), a new antirheumatic drug, has been developed. The intermediate, 2-methylene-4-(4-methylphenyl)-4-oxobutanoic acid (2), was prepared by Friedel-Crafts acylation of toluene with itaconic anhydride (3) in the presence of aluminum trichloride and nitrobenzene in 63% yield without silica gel column purification. Compound 1 was prepared by Michael addition of 2 with thioacetic acid (4) in 74% yield. Overall, 1 was obtained in 47% yield from 3. The structures and synthetic mechanisms of by-products (five compounds) of 2 were also clarified.

An alternative route for the construction of carbosilane dendrimers uniformly functionalized with lactose or sialyllactose moieties

A new approach for the formation of an acetylthio linkage on aglycon by means of a radical addition of thioacetic acid into the CC double bond of the aglycon was examined. An introduction of a carbohydrate moiety into carbosilane dendrimers was demonstrated using a one-pot coupling reaction in MeOH–DMF in the presence of NaOMe via removal of an acetyl group of the acetylthio linkage in the saccharide moieties, producing a thiolate anion and a nucleophilic replacement of the thiolate to dendric alkyl bromide to form carbosilane dendrimers uniformly bearing lactose or sialyllactose moieties through thioether linkages in high yields.

Synthesis of ω-mercapto-poly(alkylene oxide) by the Mitsunobu reaction

An efficient way to transform ω-hydroxy-poly(alkylene oxide) in ω-mercapto-poly(alkylene oxide) in two steps is described : the Mitsunobu reaction with thiolacetic acid followed by the reduction of the thiol ester. Yields are quantitative with water soluble polymers.

On the reaction of nickel(II) ions with thiolacetic acid

An unexpected mononuclear nickel thiol­ate, bis(per­thio­acetato-S,S′)nickel(II), [Ni(C2H3S3)2], has been obtained by the reaction of NiII ions with ­thiol­acetic acid. It consists of a planar rectangular NiS4 unit. Weak hydrogen bonds of the type C—H⋯Ni form molecular ribbons along the a axis. Among the products, γ-sulfur is also detected.

Evidence for the Role of Electron-Withdrawing Power of Functional Groups and [H+] for Electron-Transfer Reaction in Substituted Alkyl Sulfides

The pulse radiolysis technique has been employed to demonstrate the effects of the electron-withdrawing power of functional groups and the H+ concentration on the nature of •OH radical reaction with substituted alkyl sulfides. The intermediate OH adduct and α-thioalkyl radical could be detected in substituted sulfides having a functional group of high electron-withdrawing power. The concentration of H+ required for the formation of solute radical cations appears to correlate with the electron-withdrawing power of the functional group. The reactivity of eaq- toward dialkyl sulfides increases upon the introduction of strongly electron-withdrawing groups which effectively reduce the electron density at sulfur. The transient absorption band (λmax = 310 nm) observed from the reaction of •OH radicals with methyl thioacetic acid (MTA) is assigned to the α-thioalkyl radical formed via an intermediate OH adduct. In highly acidic solutions ([HClO4] ≥ 3 mol dm-3), •OH radicals are able to react with MTA to form dimer radical cations (λmax = 490 nm). The specific one-electron oxidants (Cl2•-, Br2•-, and SO4•-) undergo electron-transfer reaction with the solute; however, the transient absorption band of the dimer radical cation at 490 nm could not be observed, which may be due to unstable nature of the transient species in neutral and slightly acidic solutions. The oxidation potential is determined to be 1.56 V. The decay kinetics of the solute dimer radical cation is discussed in detail, and deprotonation of the solute radical cation is found to be the rate-determining step. The stability constant for the dimer radical cation has been determined to be 10 dm3 mol-1 at 25 °C. The transient species (λmax = 390 nm, k = 3.3 × 109 dm3 mol-1 s-1), formed from the reaction of Br• atom with the solute, is assigned to a three-electron-bonded Br• adduct.

Synthesis of terminally perfluorinated long-chain alkanethiols, sulfides and disulfides from the corresponding halides

Semifluorinated n-alkanethiols, symmetrical sulfides and disulfides bearing the chain(s) F(CF 2) n (CH 2) m with n=4, 6, 8, 10, and m=2, 11 have been prepared by various synthetic methods, starting from the corresponding iodides or bromides. Methods based on sodium hydrogen sulfide, commonly used to accomplish this conversion, treatment of the Bunte salt obtained from sodium thiosulfate, the basic hydrolysis of isothiouronium salts, the hydrolysis under mild conditions of thiophosphorates formed from sodium thiophosphate and the basic hydrolysis of thiol acetic acid derivatives, have been investigated and compared relatively to the selective synthesis of the title compounds. The thiolacetic route yields essentially the thiols with some amounts of disulfides. Results from thiourea appears similar. Sodium thiophosphate constitutes an excellent route for the synthesis of thioethers, particularly when starting from the bromides. The two classical methods based on sodium hydrogen sulfide and sodium thiosulfate exhibit poor selectivity. It has been possible to obtain all the sulfur compounds reported in the pure state.

Action of acid on 6-thio-hexose derivatives. Synthesis of 1,6-epithio-hexofuranoses

Reaction of 5,6-anhydro-1,2- O-isopropylidene-3- O-methanesulfonyl-β- l-idofuranose with thioacetic acid in pyridine gave 6- S-acetyl-1,2- O-isopropylidene-3- O-methanesulfonyl-6-thio-β- l-idofuranose, which was deacetylated and the resultant thiol was converted into 1,2- O:5,6- O, S-diisopropylidene-3- O-methanesulfonyl-β- l-idofuranose. Alkaline cleavage of the mesyl group gave 1,2- O: 5,6- O, S-diisopropylidene-β- l-idofuranose, which on treatment with hot dilute hydrochloric acid gave, after acetylation, 2,3,5-tri- O-acetyl-1,6-dideoxy-1,6-epithio-α- l-idofuranose and not the expected idopyranose isomer. 1,2:3,5-Di- O-isopropylidene-6- O-toluene- p-sulfonyl-α- d-glucofuranose was converted into 6- S-acetyl-1,2:3,5-di- O-isopropylidene-6-thio-α- d-glucofuranose; conversion into the 6-thiol and isomerisation in acidified acetone gave 1,2- O:5,6- O, S-diisopropylidene-6-thio-α- d-glucofuranose. Acid treatment of this diacetal, or the isomeric 1,2:3,5-di- O-isopropylidene-6-thio-α- d-glucofuranose, followed by acetylation gave 2,3,5-tri- O-acetyl-1,6-dideoxy-1,6-epithio-β- d-glucofuranose. Similar treatment of 1,2:3,4-di- O-isopropylidene-6-thio-α- d-galactopyranose gave 2,3,5-tri- O-acetyl-1,6-dideoxy-1,6-epithio-α- d-galactofuranose.