Search Results (50)

Two series of imidazole-2(3H)-thiones inspired by naturally occurring lepidiline alkaloids, bearing either one or two benzyl-type substituents located at the N(1)/N(3) atoms, respectively, were prepared and examined in reactions with in situ generated C-trifluoromethyl-N-aryl nitrile imines. N,N-Dibenzylated imidazole-2-thiones served exclusively as C=S dipolarophiles to afford hitherto unknown CF₃-functionalized spiro [1,3,4-thiadiazole-5,2′-imidazole] derivatives formed through the (3+2)-cycloaddition pathway. In contrast, the enolizable N-monobenzylated imidazole-2-thiones provided acyclic products, i.e., hydrazonothioates, resulting from nucleophilic addition of the respective en(thio)late onto the C-termini of the 1,3-dipole. The presented results extend the scope of both fluorinated products available via trapping of the in situ generated CF₃-nitrile imines as well as synthetic analogues of lepidilines. In addition, spectroscopic analysis of the obtained products and the known related systems revealed ¹³C NMR chemical shifts attributed to the C-(CF₃) atom as useful probes to differentiate the open-chain hydrazonothioates (δ = 112–120), 2,2-diaryl/dialkyl-2,3-dihydro-1,3,4-thiadiazoles (δ = 130–145), and more strained spiro-1,3,4-thiadiazole derivatives (δ = 166–170) reported herein. Full article

The metabolic cycle of L-proline plays a crucial role in cancer cell survival, proliferation, and metastasis. A key intermediate in the biosynthesis and degradation of proline is 3,4-dihydro-2H-pyrrole-2-carboxylic acid. A direct route for synthesizing substituted derivatives of this acid involves the cyclization of 2-amino-5-oxonitriles. Michael additions of [(diphenylmethylene)amino]acetonitrile to enones in a basic medium—either with aqueous sodium hydroxide or under solid–liquid phase-transfer catalysis conditions using CaO as a base—enable the synthesis of substituted 2-amino-5-oxonitriles as single diastereoisomers or as diastereoisomeric mixtures. Selective removal of the diphenylmethylene-protecting group, followed by in situ cyclization in acidic conditions, yields trans- and cis-3,5-diaryl-3,4-dihydro-2H-pyrrole-2-carbonitriles. The reaction of nitriles with HCl/dioxane/methanol followed by treatment with water produces esters and amides as by-products. In vitro screening of the synthesized compounds against multiple human cancer cell lines revealed that some compounds exhibit a good or high selectivity index. In conclusion, the synthetic schemes presented offer simple and efficient routes for the preparation of the derivatives of substituted 3,4-dihydro-2H-pyrrole-2-carboxylic acids, with some compounds exhibiting promising antiproliferative activity. Full article

It was shown for the first time that diaryl(hetaryl)ketones are capable of directly phosphorylating with red phosphorus in the superbase suspension KOH/DMSO(H₂O) at 85 °C for 1.5 h to afford potassium bis(diaryl(hetaryl)methyl)phosphates that were earlier inaccessible in a yield of up to 45%. The ESR data demonstrate that unlike previously published phosphorylation with elemental phosphorus, this new phosphorylation reaction proceeds via a single electron transfer from polyphospide anions to diaryl(hetaryl)ketones. This is the first example of the C-O-P bond generation during the phosphorylation with elemental phosphorus in strongly basic media, which usually provides C-P bond formation. Full article

The so far unattended version of the Hirao reaction involving the coupling of the less reactive chloroarenes with >P(O)H reagents, such as diarylphosphine oxides, diethyl phosphite, and ethyl phenyl-H-phosphinate, was investigated in detail using Pd(OAc)₂ as the catalyst precursor, and applying some excess of the P-reagent to provide the ligand via its trivalent tautomeric (>P-OH) form. In the presence of triethylamine, no P–C coupling took place, meaning that there was a need for a stronger base, an alkali carbonate. The solvent had a significant effect on the efficiency of the Hirao reaction. The optimum conditions (10% of the Pd(OAc)₂, 1.3 equiv. of the P-reagent, 1.1 equiv. of the alkali carbonate, 135–150 °C) explored herein were applied in the synthesis of diaryl-phenylphosphine oxides, aryl-diphenylphosphine oxides, diethyl arylphosphonates, and ethyl diphenylphosphinate. Theoretical calculations performed at the M06-2X/6-31G(d,p)[PCM(MeCN)] level also justified coupling with the chloroarenes under appropriate conditions, and were in accord with the experimental results revealing the unsuitability of triethylamine as a base and the need for an alkali carbonate. The new protocol elaborated herein is more practical and “greener” than the version with bromoarenes, and embraces a wide substrate scope. Full article

Organic compounds with 1,3-diketone or 3-amino enone functional groups are extremely important as they can be converted into a plethora of carbo- or heterocyclic derivatives or can be used as ligands in the formation of metal complexes. Here, we have achieved the preparation of a series of non-symmetrical β-ketoenamines (O,N,N proligand) of the type (4-MeOC₆H₄)C(=O)CH=C(R)NH(Q) obtained through the Schiff base condensation of 1,3-diketones (1-anisoylacetone, 1-anisyl-3-(4-cyanophenyl)-1,3-propanedione, and 1-anisyl-3-(4,4,4-trifluorotolyl)-1,3-propanedione) functionalized with electron donor and electron-withdrawing substituents and 8-aminoquinoline (R = CH₃, 4-C₆H₄CN, 4-C₆H₄CF₃; Q = C₉H₇N). Schiff base ketoimines with a pendant quinolyl moiety were isolated as single regioisomers in yields of 22–56% and characterized with FT-IR, ¹H NMR, and UV-visible spectroscopy, as well as single-crystal X-ray crystallography, which allowed for the elucidation of the nature of the isolated regioisomers. The regioselectivity of the condensation of electronically unsymmetrical 1,3-diaryl-1,3-diketones with 8-aminoquinoline was studied by ¹H NMR, providing regioisomer ratios of ~3:1 and ~2:1 in the case of CN and CF₃ substituents, respectively. The electronic effects correlate well with the difference between the Hammett σ⁺ coefficients of the two para substituents on the aryl rings. Full article

The characterization of lignocellulosic biomass present in archaeological wood is crucial for understanding the degradation processes affecting wooden artifacts. The lignocellulosic fractions in both the external and internal parts of Moroccan archaeological cedar wood (9th, 12th, and 21st centuries) were characterized using infrared spectroscopy (FTIR-ATR deconvolution mode), X-ray diffraction (XRD), and SEM analysis. The XRD demonstrates a significant reduction in the crystallinity index of cellulose from recent to aging samples. This finding is corroborated by the FTIR analysis, which shows a significant reduction in the area profiles of the C-H crystalline cellulosic bands (1374, 1315, and 1265 cm⁻¹) and C-O-C (1150–1000 cm⁻¹). The alterations in the lignin fraction of aging samples (from the 9th and 12th centuries) were demonstrated by a reduction in the intensity of the bands at 1271 and 1232 cm⁻¹ (C_ar-O) and the formation of new compounds, such as quinones and/or diaryl carbonyl structures, within the 1700–1550 cm⁻¹ range. The SEM images of cedar wood samples from the 9th and 12th centuries reveal voids, indicating that the entire cell wall component has been removed, a characteristic feature of simultaneous white rot fungi. In addition, horizontal “scratches” were noted, indicating possible bacterial activity. Full article

In this work, we applied commercially available 2-pyridinecarboxylic acid to modify cellulose by simple manipulations, and then anchored low-toxicity metal nickel onto the modified cellulose to prepare the heterogeneous catalyst (CL-AcPy-Ni). The obtained catalyst was characterized by FT-IR, TG-DSC, BET, XRD, SEM-EDS, ICP-OES, XPS, and GPC. The catalytic performance of CL-AcPy-Ni in the Suzuki cross-coupling reaction was investigated using 4-methyl iodobenzene and phenylboronic acid as the model substrates reacting in THF under 120 °C for 24 h. The catalytic ability of CL-AcPy-Ni for various halobenzenes and phenylboronic acid derivatives was also further investigated under optimal conditions and demonstrated good catalytic activity, and a series of diaryls were successfully synthesized. Finally, this green nickel-based catalyst could be reused for five successive cycles by simple centrifugation. Full article

Synthesis of 3,8-diaryl-2H-cyclohepta[b]furan-2-ones was accomplished by the one-pot procedure involving sequential iodation and Suzuki–Miyaura coupling reactions. The optical and structural characteristics of 3,8-diaryl-2H-cyclohepta[b]furan-2-ones prepared were scrutinized using UV/Vis spectroscopy, theoretical calculations, and single-crystal X-ray crystallography. The redox properties of the compounds were also evaluated through cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The findings reveal that the introduction of aryl groups at both the 3- and 8-positions significantly influences the electronic properties of the CHFs, resulting in distinct optical and electrochemical characteristics. Full article

2,6-Diaryl-4H-tetrahydro-thiopyran-4-ones and corresponding sulfoxide and sulfone derivatives were designed to lower the major toxicity of their parent anti-kinetoplatidal diarylideneacetones through a prodrug effect. Novel diastereoselective methodologies were developed and generalized from diarylideneacetones and 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones to allow the introduction of a wide substitution profile and to prepare the related S-oxides. The in vitro biological activity and selectivity of diarylideneacetones, 2,6-diaryl-4H-tetrahydro-thiopyran-4-ones, and their S-sulfoxide and sulfone metabolites were evaluated against Trypanosoma brucei brucei, Trypanosoma cruzi, and various Leishmania species in comparison with their cytotoxicity against human fibroblasts hMRC-5. The data revealed that the sulfides, sulfoxides, and sulfones, in which the Michael acceptor sites are temporarily masked, are less toxic against mammal cells while the anti-trypanosomal potency was maintained against T. b. brucei, T. cruzi, L. infantum, and L. donovani, thus confirming the validity of the prodrug strategy. The mechanism of action is proposed to be due to the involvement of diarylideneacetones in cascades of redox reactions involving the trypanothione system. After Michael addition of the dithiol to the double bonds, resulting in an elongated polymer, the latter—upon S-oxidation, followed by syn-eliminations—fragments, under continuous release of reactive oxygen species and sulfenic/sulfonic species, causing the death of the trypanosomal parasites in the micromolar or submicromolar range with high selectivity indexes. Full article

Through the implementation of a one-pot strategy, five examples of non-symmetrical [N,N-diaryl-11-phenyl-1,2,3,7,8,9,10-heptahydrocyclohepta[b]quinoline-4,6-diimine]iron(II) chloride complexes (aryl = 2,6-Me₂Ph Fe1, 2,6-Et₂Ph Fe2, 2,6-i-Pr₂Ph Fe3, 2,4,6-Me₃Ph Fe4, and 2,6-Et₂-4-MePh Fe5), incorporating fused six- and seven-membered carbocyclic rings and appended with a remote para-phenyl group, were readily prepared. The molecular structures of Fe2 and Fe3 emphasize the variation in fused ring size and the skewed disposition of the para-phenyl group present in the N′,N,N″-ligand support. Upon activation with MAO or MMAO, Fe1–Fe5 all showed high catalytic activity for ethylene polymerization, with an exceptional level of 35.92 × 10⁶ g (PE) mol⁻¹ (Fe) h⁻¹ seen for mesityl-substituted Fe4/MMAO operating at 60 °C. All catalysts generated highly linear polyethylene with good control of the polymer molecular weight achievable via straightforward manipulation of run temperature. Typically, low molecular weight polymers with narrow dispersity (M_w/M_n = 1.5) were produced at 80 °C (MMAO: 3.7 kg mol⁻¹ and MAO: 4.9 kg mol⁻¹), while at temperatures between 40 °C and 50 °C, moderate molecular weight polymers were obtained (MMAO: 35.6–51.6 kg mol⁻¹ and MAO: 72.4–95.5 kg mol⁻¹). Moreover, analysis of these polyethylenes by ¹H and ¹³C NMR spectroscopy highlighted the role played by both β-H elimination and chain transfer to aluminum during chain termination, with the highest rate of β-H elimination seen at 60 °C for the MMAO-activated system and 70 °C for the MAO system. Full article

The concise and highly convergent synthesis of the isodityrosine unit of seongsanamide A–D and its derivatives bearing a diaryl ether moiety is described. In this work, the synthetic strategy features palladium-catalyzed C(sp³)–H functionalization and a Cu/ligand-catalyzed coupling reaction. We report a practical protocol for the palladium-catalyzed mono-arylation of β-methyl C(sp³)–H of an alanine derivative bearing a 2-thiomethylaniline auxiliary. The reaction is compatible with a variety of functional groups, providing practical access to numerous β-aryl-α-amino acids; these acids can be converted into various tyrosine and dihydroxyphenylalanine (DOPA) derivatives. Then, a CuI/N,N-dimethylglycine-catalyzed arylation of the already synthesized DOPA derivatives with aryl iodides is described for the synthesis of isodityrosine derivatives. Full article

Among the methods used for the synthesis of functionalized heterocyclic compounds, photochemistry has gained immense popularity due to the reactivity of intermediates in photoinduced reactions. In this study, we report on the effect of diaryl disulfides as hydrogen atom transfer catalysts on the photoinduced transformations of pyrazolo[1,2-a]pyrazolones. After excitation with visible light, these compounds are susceptible to C–N bond cleavage, followed by intermolecular hydrogen atom abstraction. By modifying the reaction conditions, we have developed two novel methods for the synthesis of highly substituted pyrazoles. Full article

A simple and efficient hydroxide-mediated S_NAr rearrangement was reported to synthesize new depside derivatives containing the diaryl ether skeleton from the natural product barbatic acid. The prepared compounds were determined using ¹H NMR, ¹³C NMR, HRMS, and X-ray crystallographic analysis and were also screened in vitro for cytotoxicity against three cancer cell lines and one normal cell line. The evaluation results showed that compound 3b possessed the best antiproliferative activity against liver cancer HepG2 cell line and low toxicity, which made it worth further study. Full article

Diaryl-furanones are specific analytical reagents for the biochemical detection of primary amines by fluorescence techniques. Well-known reagents are fluorescamine (Fluram) and 2-methoxy-2,4-diphenyl-3(2H)-furanone (MDPF), yielding fluorescent products with λem at 480–490 nm. Although the reaction products claim to be pyrrolinones, recent studies show that they are really 3-oxopyrrole (pyrrolone) derivatives. Both reagents have been used for the cytochemical demonstration of primary amines. In this work, we have applied the fluorescent products of MDPF with amines (n-butylamine, BA; glucosamine, GA; and spermine, Sp), which showed interesting fluorescence reactions with chromatin DNA. 2,4-diphenyl-3-oxopyrrole products (diPOPy) can be easily synthesized according to well-known procedures, by mixing solutions of MDPF in acetone with water at pH 9 containing the amino compounds. DiPOPy derivatives of BA, GA, and Sp were used for spectroscopic, microscopic, and molecular modeling studies, showing a bright and selective blue–green fluorescence on DNA substrates, mainly chromatin, kinetoplast DNA, and stretched chromatin fibers. The cationic diPOPy fluorophore is planar, with a high partial positive charge in the N atom, and suitable for intercalative binding to DNA. A mechanism of fluorescamine fluorescence due to an inner-salt isomeric form is proposed, and an astonishing correlation between adenine–thymine-rich centromeric heterochromatin in mouse metaphase chromosomes after reaction of the fluorescamine reagent with protein amino groups is also discussed. Full article

Photodynamic Antimicrobial Chemotherapy (PACT) has received great attention in recent years since it is an effective and promising modality for the treatment of human oral and skin infections with the advantage of bypassing pathogens’ resistance to antimicrobials. Moreover, PACT applications demonstrated a certain activity in the inhibition and eradication of biofilms, overcoming the well-known tolerance of sessile communities to antimicrobial agents. In this study, 13 diaryl-porphyrins (mono-, di-cationic, and non-ionic) P1–P13 were investigated for their potential as photosensitizer anti-Staphylococcus aureus. The efficacy of the diaryl-porphyrins was evaluated through photo-inactivation tests. Crystal-violet staining combined with viable count techniques were aimed at assaying their anti-biofilm activity. Among the tested compounds, the neutral photosensitizer P4 was better than the cationic ones, irrespective of their corresponding binding rates. In particular, P4 was active in inhibiting the biofilm formation and in impairing the viability of the adherent and planktonic populations of a 24 h old biofilm. The inhibitory activity was also efficient against a methicillin resistant S. aureus strain. In conclusion, the diaryl-porphyrin family represents a reservoir of promising compounds for photodynamic applications against the pathogen S. aureus and in preventing the formation of biofilms that cause many infections to become chronic. Full article