Thioamide Derivatives Research Articles

Synthesis of some fluorinated thiazolopyridine from pentafluoropyridine and 4-phenylsulfonyl tetrafluoropyridine

In this study, the reaction of pentafluoropyridine and 4-phenylsulfonyl tetrafluoropyridine with difunctional nitrogen and sulfur nucleophiles such as thiourea, thioamide derivatives, and unsymmetrical bidentate nitrogen nucleophiles such as diamino-triazole and amino-imidazole in the presence of sodium carbonate was investigated.

Preparation and structural analysis of (±)-cis-ethyl 2-sulfanylidenedecahydro-1,6-naphthyridine-6-carboxylate and (±)-trans-ethyl 2-oxooctahydro-1H-pyrrolo[3,2-c]pyridine-5-carboxylate.

Bicycle ring closure on a mixture of (4aS,8aR)- and (4aR,8aS)-ethyl 2-oxodecahydro-1,6-naphthyridine-6-carboxylate, followed by conversion of the separated cis and trans isomers to the corresponding thioamide derivatives, gave (4aSR,8aRS)-ethyl 2-sulfanylidenedecahydro-1,6-naphthyridine-6-carboxylate, C11H18N2O2S. Structural analysis of this thioamide revealed a structure with two crystallographically independent conformers per asymmetric unit (Z'= 2). The reciprocal bicycle ring closure on (3aRS,7aRS)-ethyl 2-oxooctahydro-1H-pyrrolo[3,2-c]pyridine-5-carboxylate, C10H16N2O3, was also accomplished in good overall yield. Here the five-membered ring is disordered over two positions, so that both enantiomers are represented in the asymmetric unit. The compounds act as key intermediates towards the synthesis of potential new polycyclic medicinal chemical structures.

Development of tertiary thioamide derivatives to recover palladium(II) from simulated complex chloride solutions

Two thioamide derivatives, N-methyl-N-phenyl-octanthioamide (MPHTA) and N-methyl-N-cyclohexyl-octanthioamide (MCHTA), were synthesized from their amide analogues, adequately characterized, and systematically evaluated as extractants for palladium(II) from chloride media. In sequence of previous research, which revealed the adequacy of both compounds, when dissolved in toluene, to efficiently recover Pd(II) from a wide range of differently concentrated hydrochloric acid solutions, the Pd(II) solvent extraction performance of both MPHTA and MCHTA dissolved in commercial diluents is evaluated in this work. Additionally, results obtained on successive extraction–stripping cycles, involving thiourea as stripping agent, confirm the robustness and stability of these Pd(II) solvent extraction systems, even when commercial diluents are employed. Equilibrium extraction isotherms, obtained for both compounds in toluene, show a high Pd(II) loading capacity. Selectivity data has been collected for complex 4.0M and 6.0M HCl mixtures containing two, three, four or five metal ions — palladium(II), platinum(IV), rhodium(III), aluminum(III), and iron(III). Fe(III) is the only metal that affects Pd(II) extraction of both MPHTA and MCHTA, as Pd(II) distribution ratios are significantly reduced; on the other hand, the other metals are practically not extracted. These selectivity results are encouraging from a practical point of view, since both extractants may prove suitable to efficiently and selectively recover Pd(II) from hydrometallurgical solutions coming from the leaching of secondary raw material sources.

3,4-Dimethyl-2,5-functionalized thieno[2,3-b]thiophenes: versatile precursors for novel bis-thiazoles

Synthesis of novel bis(thiazoles) 19–22, 24, 25, 30 and 31 is reported. Thus, reaction of the bis(α-bromoketones) 14 and 15 with the corresponding thioamide derivatives 16–18 in refluxing EtOH in the presence of triethylamine afforded 19–22 in good yields. On the other hand, the novel bis(thiazoles) 24 and 25 can be synthesized by the reaction of 14 and 15 with the corresponding p-chlorobenzaldehyde thiosemicarbazones 23 in refluxing EtOH. The novel isomeric bis(thiazoles) 30 and 31 can also be synthesized by a reaction of the corresponding bis(benzaldehyde thiosemicarbazones) 27 and 28 with p-chlorophenacyl bromide 29. Compounds 27 and 28 were obtained by condensation of the corresponding bis(aldehydes) 12 and 13 with thiosemicarbazide 26.

Theoretical study of charge transfer complexes between antithyroid thioamides and TCNE: Thermodynamics of the complex formation

Thermodynamic characteristics of charge transfer complexes formed between both mono and bicyclic thioamides as donors and tetracyanoethylene have been studied by selected density functional theory and wave-function based methods combined with the polarizable continuum model. The thioamide derivatives are known to exhibit significant antithyroid activity. The equilibrium constants of complex formation (K) derived from calculated thermodynamic parameters nicely correlate with the donor strength while their experimental counterparts reveal practically no correlation. Based on theoretical calculations we conclude that the rather erratic behavior of the experimental K values is related to the presence of chemical reactions including radical ions formation, which proceed along with the π-complex formation.

Crystal structure, FT-IR, FT-Raman, 1H NMR and computational study of ethyl 2-{[(Z)3-(4-chlorophenyl)-3-hydroxy-2-propene-1-thione] amino} acetate

The molecular structure of a thioamide derivative ethyl 2-{[(Z)3-(4-chlorophenyl)-3-hydroxy-2-propene-1-thione] amino} acetate was determined by X-ray diffraction. The proton NMR (1H NMR), Fourier Transform Infra-Red (FT-IR) and Fourier Transform Raman (FT-Raman) spectra of the compound were recorded and analyzed. The conjugated enol form of the compound was crystallized in the monoclinic space group P21/c, with unit cell dimensions a=12.514(2)Å, b=5.403(5)Å, c=21.233(3)Å, β=94.597(4)°. The structure was solved by direct methods and refined to the R value of 0.0462. The thioamide moiety in the compound adopts the Z-conformation and the CN bond shows a high rotational barrier. The geometry in the gas phase was optimized by B3LYP and RHF quantum mechanical calculations using Gaussian 09 programme and the vibrational frequencies were calculated. The experimental and theoretical data are in good agreement.

Selenorhodamine photosensitizers for photodynamic therapy of P-glycoprotein-expressing cancer cells.

We examined a series of selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenorhodamine core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their colocalization with mitochondrial specific agents in Colo-26 cells. Thioamide derivatives 16b and 18b were more effective photosensitizers than amide derivatives 15b and 17b. Selenorhodamine thioamides 16b and 18b were useful in a combination therapy to treat Colo-26 cells in vitro: a synergistic therapeutic effect was observed when Colo-26 cells were exposed to PDT and treatment with the cancer drug doxorubicin.

Cloud point extraction of some precious metals using Triton X-114 and a thioamide derivative with a salting-out effect

A cloud point extraction procedure is proposed for preconcentration of trace amounts of palladium (II), silver (I) and gold (III) in aqueous medium. The metal ions in the initial aqueous solution were extracted using the non-ionic surfactant, Triton X-114 after complex formation with 4-(p-chlorophenyl)-1-(pyridin-2-yl)thiosemicarbazide at pH 6.0 in the presence of 0.3 mol L−1 sodium sulfate as a salting-out agent at 25 °C. Dilution of the surfactant-rich phase with acidified methanol was performed after phase separation, and the metal ions were determined by electrothermal atomic absorption spectrometry. The main factors affecting extraction procedure, such as pH, concentration of the ligand, and amount of Triton X-114 were studied in detail. Under the optimum experimental conditions, the calibration graphs were linear upto 125, 50 and 100 μg L−1 and the enrichment factors were 52, 46 and 56 for palladium, silver and gold, respectively. The limits of detection, based on three times of standard deviation of blank signal by 10 replicate measurements divided by the slope of calibration curves were 0.12, 0.08 and 0.30 μg L−1 for palladium, silver and gold, respectively. The accuracy of the results was verified by analyzing spiked water samples. The proposed method has been applied for the determination of the metal ions in soil and rock samples with satisfactory results.

Bis(α‐bromo ketones): Versatile Precursors for Novel Bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) and Bis(thiazoles)

A synthesis of novel bis(s‐triazolo[3,4‐b][1,3,4]thiadiazines) 4, 5, 6 in which the triazolothiadiazine is linked to the benzene core through the thiadiazine ring via phenoxymethyl spacers was reported. First attempt to synthesize 4, 5, 6 by the reaction of the appropriate bis(acetophenones) with 4‐amino‐3‐mercapto‐1,2,4‐triazole derivatives using an acidified acetic acid method were unsuccessful. On the other hand, reaction of the corresponding bis(α‐bromoketones) with 4‐amino‐3‐mercapto‐1,2,4‐triazole derivatives afforded 4, 5, 6 in good yields. The reaction pathway is assumed to involve S‐alkylation to give bis(aminotriazole) intermediates, followed by intramolecular cyclocondensation to give 4, 5, 6. The successful isolation of the corresponding bis(aminotriazole) intermediates provides strong evidence for the proposed mechanism. The novel bis(thiazoles) 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, linked to alkyl or aryl spacers can also be synthesized by reaction of the appropriate bis(bromoacetyl) compounds 12a, 12b, 12c and 14, 15, 16, 17, 18, 19 with the corresponding thioamide derivatives 20, 21, 22.

Synthesis of Ferrocenyl and Ruthenocenyl Thioamide Derivatives Using a Single-Step Three-Component Reaction

The efficient syntheses of various metallocenyl thioamides using a single-step three-component condensation reaction between the commercially available (dimethylaminomethyl)ferrocene or aminomethylferrocene and another organic amine in the presence of elemental sulfur are described. All new organometallic thioamide derivatives were unambiguously characterized by 1H and 13C NMR spectroscopy and mass spectrometry. Furthermore, the structures of five ferrocenyl thioamides determined by X-ray crystallography are presented.

Nano n-propylsulfonated magnetic γ-Fe2O3 as an efficient and reusable catalyst for the synthesis of thioamides

One-pot three-component reactions of aldehydes, amines, and sulfur are carried out in the presence of nano n-propylsulfonated magnetic γ-Fe2O3 as a catalyst for the synthesis of biologically interesting thioamide derivatives. The value of this catalytic method lies in its mild reaction catalyst and conditions, good yields, and ease of handling.

Synthesis and cytotoxicity studies of novel benzhydrylpiperazine carboxamide and thioamide derivatives

Synthesis and cytotoxic activities of 32 benzhydrylpiperazine derivatives with carboxamide and thioamide moieties were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. In general, 4-chlorobenzhydrylpiperazine derivatives were more cytotoxic than other compounds. In addition, thioamide derivatives (6a–g) have higher growth inhibition than their carboxamide analogs.

Solid-Contact Ion-Selective Electrodes with Highly Selective Thioamide Derivatives of p-tert-Butylcalix[4]arene for the Determination of Lead(II) in Environmental Samples

Thioamide derivatives of p-tert-butylcalix[4]arene were used as ionophores in the development of solid-contact ion-selective electrodes based on conducting polymer poly(3,4-ethylenedioxythiophene)/polystyrene sulfonate (PEDOT/PSS) which was synthesized by electrodeposition on the glassy carbon electrodes. The typical ion-selective membranes with optionally two different plasticizers [bis(2-ethylhexyl)sebacate (DOS) and 2-nitrophenyl octyl ether (NPOE)] were investigated. The potentiometric selectivity coefficients were determined by separate solution method (SSM) for Pb(2+) over Cu(2+), Cd(2+), Ca(2+), Na(+), and K(+). High selectivity toward Pb(2+) was obtained. By applying two conditioning protocols, a low detection limit log(a(DL)) ≈ -9 was achieved. The fabricated ion-selective electrodes were used to determine Pb(2+) concentration in environmental samples. The obtained results were compared to analysis done by inductively coupled plasma mass spectrometry (ICPMS).

A new parameter that supports speculation on the possible mechanism of hypothyroidism induced by chemical substances in repeated-dose toxicity studies

Hypothyroidism induced by xenobiotic treatment was analyzed for possible underlying mechanism(s) on the basis of different responses of the thyroid gland and the liver, using a newly-created database of repeated-dose toxicity of 500 chemicals. Two mechanisms are proposed: direct inhibition of thyroid hormone biosynthesis in the thyroid gland, and stimulated degradation of thyroid hormone by induction of hepatic drug-metabolizing enzymes. In the database there were 10 chemicals inducing hypertrophy/hyperplasia of follicular cells in the thyroid gland and having data on thyroid glands. On the basis of the chemical structure and information available in the literature, we judged three chemicals to be typical thioamide derivatives that act directly on the thyroid gland, and the others as non-thioamide derivatives that were unlikely to have any direct action on the thyroid gland. All these chemicals were classified into two groups using the ratios of relative weight increase rate of thyroid gland versus that of the liver. These values were at least 1.7, but 3.2 or more in the most of the cases for thioamide derivatives, and 1.2 or less for non-thioamide derivatives. This background analysis suggests the feasibility of parameter-supported speculation on the possible underlying mechanism when new repeated-dose toxicity data on hypothyroidism becomes available.

ChemInform Abstract: Synthesis of Novel Thioamidoalkyl‐ and Thiocarbamidoalkyl Naphthols via a Three‐Component Condensation Reaction Using Heterogeneous Catalyst of Ferric Hydrogensulfate.

Abstract Ferric hydrogensulfate [Fe(HSO4)3] was used as a suitable heterogeneous catalyst for the one-pot multicomponent reaction of β-naphthol, aromatic aldehydes, and thioamide derivatives to obtain the corresponding thioamidoalkyl naphthols. Various novel thioamidoalkyl naphthols and thiocarbamidoalkyl naphthols were synthesized in good yields from thioacetamide and thiourea. The heterogeneous nature of the catalyst made it reusable for further chemical reactions.

Selective signaling of peracetic acid over hydrogen peroxide by desulfurization of an anthracene-thioamide

Selective signaling of peracetic acid by desulfurization of a thioamide was investigated. A thioamide derivative of anthracene 1 was efficiently desulfurized by peracetic acid to the corresponding amide 2, which resulted in a pronounced turn-on type fluorescent signaling. Signaling was not affected by the presence of another important oxidant hydrogen peroxide thereby providing selective signaling of the peracetic acid from its frequent contaminant hydrogen peroxide. Anthracene-thioamide 1 also provided selectivity for peracetic acid over commonly encountered metal ions and anions. The chemical transformation was confirmed by 1H NMR, 13C NMR, and fluorescence measurements.

Synthesis of Novel Thioamidoalkyl- and Thiocarbamidoalkyl Naphthols via a Three-Component Condensation Reaction Using Heterogeneous Catalyst of Ferric Hydrogensulfate

Ferric hydrogensulfate [Fe(HSO4)3] was used as a suitable heterogeneous catalyst for the one-pot multicomponent reaction of β-naphthol, aromatic aldehydes, and thioamide derivatives to obtain the corresponding thioamidoalkyl naphthols. Various novel thioamidoalkyl naphthols and thiocarbamidoalkyl naphthols were synthesized in good yields from thioacetamide and thiourea. The heterogeneous nature of the catalyst made it reusable for further chemical reactions.

TiCl4-promoted desulfurization of thiocarbonyls and oxidation of sulfides in the presence of H2O2

H2O2 in combination with TiCl4 proved to be a highly reactive reagent system for the desulfurization of thioamide and thioketone derivatives in excellent yields and short reaction times with high purity. Sulfides were also found to undergo oxidation to sulfones under similar reaction conditions. In most cases, these reactions are highly selective, simple, and clean, affording products in high yields and purity.

Fluorescence Signaling of Zr4+ by Hydrogen Peroxide Assisted Selective Desulfurization of Thioamide

Thioamide derivative with a pyrene fluorophore was smoothly transformed to its corresponding amide by Zr(4+) ions in the presence of hydrogen peroxide. The transformation was evidenced by (1)H NMR spectroscopy and the signaling was completed within 10 min after sample preparation. Interference from Ag(+) and Hg(2+) ions in Zr(4+)-selective fluorescence signaling was readily suppressed with the use of Sn(2+) as a reducing additive. Discrimination of Zr(4+) from closely related hafnium, which is a frequent contaminant in commercial zirconium, was not possible. Prominent Zr(4+)-selective turn-on type fluorescence signaling was possible with a detection limit of 4.6 × 10(-6) M in an aqueous 99% ethanol solution.

Total synthesis of [Ψ[C(═S)NH]Tpg4]vancomycin aglycon, [Ψ[C(═NH)NH]Tpg4]vancomycin aglycon, and related key compounds: reengineering vancomycin for dual D-Ala-D-Ala and D-Ala-D-Lac binding.

The total synthesis of [Ψ[C(═S)NH]Tpg(4)]vancomycin aglycon (8) and its unique AgOAc-promoted single-step conversion to [Ψ[C(═NH)NH]Tpg(4)]vancomycin aglycon (7), conducted on a fully deprotected substrate, are disclosed. The synthetic approach not only permits access to 7, but it also allows late-stage access to related residue 4 derivatives, alternative access to [Ψ[CH(2)NH]Tpg(4)]vancomycin aglycon (6) from a common late-stage intermediate, and provides authentic residue 4 thioamide and amidine derivatives of the vancomycin aglycon that will facilitate ongoing efforts on their semisynthetic preparation. In addition to early stage residue 4 thioamide introduction, allowing differentiation of one of seven amide bonds central to the vancomycin core structure, the approach relied on two aromatic nucleophilic substitution reactions for formation of the 16-membered diaryl ethers in the CD/DE ring systems, an effective macrolactamization for closure of the 12-membered biaryl AB ring system, and the defined order of CD, AB, and DE ring closures. This order of ring closures follows their increasing ease of thermal atropisomer equilibration, permitting the recycling of any newly generated unnatural atropisomer under progressively milder thermal conditions where the atropoisomer stereochemistry already set is not impacted. Full details of the evaluation of 7 and 8 along with several related key synthetic compounds containing the core residue 4 amidine and thioamide modifications are reported. The binding affinity of compounds containing the residue 4 amidine with the model D-Ala-D-Ala ligand 2 was found to be only 2-3 times less than the vancomycin aglycon (5), and this binding affinity is maintained with the model d-Ala-d-Lac ligand 4, representing a nearly 600-fold increase in affinity relative to the vancomycin aglycon. Importantly, the amidines display effective dual, balanced binding affinity for both ligands (K(a)2/4 = 0.9-1.05), and they exhibit potent antimicrobial activity against VanA resistant bacteria ( E. faecalis , VanA VRE) at a level accurately reflecting these binding characteristics (MIC = 0.3-0.6 μg/mL), charting a rational approach forward in the development of antibiotics for the treatment of vancomycin-resistant bacterial infections. In sharp contrast, 8 and related residue 4 thioamides failed to bind either 2 or 4 to any appreciable extent, do not exhibit antimicrobial activity, and serve to further underscore the remarkable behavior of the residue 4 amidines.