Journal of Chemical Research

Convenient syntheses of quinazoline, benzothiazole, thiadiazole, imidazole, and thiourea derivatives starting from 3-(thiophen-2-yl)prop-2-enoyl isothiocyanate are described. The structures of the synthesized compounds are confirmed from their microanalytical and spectral data. Some of the products are examined for their antibacterial activity against Gram-positive and Gram-negative bacteria and fungi.

A series of 6-alkoxy-3-aryl-[1,2,4]triazolo[4,3-b][1,2,4,5] tetrazine derivatives is synthesized and evaluated for their antitumor activities. These compounds exhibit potent antiproliferative activities against A549, Bewo, and MCF-7 cells. Molecular docking is performed to study the inhibitor–c-Met kinase interactions, and the results show that 6-ethoxyl-3-phenylethyl-[1,2,4]triazolo[4,3-b][1,2,4,5] tetrazine is potently bound to c-Met kinase with two hydrogen bonds and one π–π interaction. Based on these preliminary results, it is thought that compound 6-ethoxyl-3-phenylethyl-[1,2,4]triazolo[4,3-b][1,2,4,5] tetrazine with potent inhibitory activity may be a potential anticancer agent.

The density functional theory (at the B3LYP level using 6-311++G(2d,2p) basis set) was used for the investigation of the geometry and electronic properties of the carvone. The electronic properties and chemical activity of the titled compound were investigated by means of several theoretical approaches, molecular electrostatic potential surface, natural bond orbital, and frontier molecular orbital analyses. It was established that the oxygen atom in the structure characterized the electrophilic reactivity; the positive regions are localized on the hydrogen atoms, which can be considered as possible sites for nucleophilic attack. A detailed analysis of the intermolecular interactions via Hirshfeld surface analysis and fingerprint plots revealed that the carvone structure is stabilized mainly by the formation of O. . .H/H. . .O hydrogen bonds. However, close contacts were established between C. . .H/H. . .C and H. . .H contacts.

Two complexes of N¹-(2-aminoethyl)propane-1,3-diamine (AEPD), [Ni(AEPD)₂](NO₃)₂ (1) and [Cu₂(μ-Cl)₂(AEPD)₂](NO₃)₂·2H₂O (2), are prepared and identified by elemental analysis, Fourier transform infrared spectroscopy and UV–Vis spectroscopy, and single-crystal X-ray diffraction (for 2). Spectral and structural data reveal that the AEPD ligand transfers from nickel to copper in the reaction between 1 and copper chloride. All coordination modes of the AEPD-based ligands are studied by analysis of the Cambridge Structural Database. The nickel atom in 1 has octahedral geometry (NiN₆) while X-ray structure analysis revealed that the copper atom in the binuclear structure of 2 has an elongated square-pyramidal geometry with a CuN₃OCl₂ environment. In the crystal network of 2, water molecules and cationic complex units along with the nitrate ions form different hydrogen bond motifs. The thermodynamic stability of the compounds and their charge distribution patterns is studied by density functional theory and natural bond orbital analysis. The ability of AEPD and its complexes to interact with 10 selected biomacromolecules is investigated by docking calculations.

Novel chiral fluorescent sensors are synthesized from a dibromide containing a tetraphenylethylene moiety and enantiomerically pure amino alcohols and an amine. The sensors are applied for the chiral recognition of a wide range of chiral carboxylic acids and related derivatives.

A simple and efficient process for direct generation of various S-thiocarbamates is developed by cross-coupling of readily available sulfonyl chlorides with cyclohexyl isocyanide. The yields are excellent and the structures of the generated S-thiocarbamates are characterized by nuclear magnetic resonance spectroscopy, infrared spectroscopy, and high-resolution mass spectrometry together with X-ray crystallographic analysis. The protocol has the advantages of using easily available reagents, employs inexpensive KI as the reagent, demonstrates good functional group tolerance, and utilizes mild reaction conditions.

On the basis of 2-benzyl-6-hydroxypyridazin-3(2H)-one, a series of its novel O-substituted (including 6-(1,3,5-triazin-2-yl)oxy) derivatives is prepared. It is proven that the substitution reactions in the initial compound occur mainly at the oxygen atom of the hydroxy group. On the basis of the obtained oxy-aceto(propane)hydrazides, the corresponding azides and anilides are synthesized. A series of 2-[(1-benzyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy]-N′-(substituted benzylidene)aceto(propane)hydrazides is obtained via the reaction of various aromatic aldehydes with the same hydrazides. Heterocyclization of the latter affords compounds with a combination of pyridazine and 1,3,4-oxadiazole rings in the molecule. The reaction of oxy-acetohydrazide with potassium thiocyanate and a mixture of CS₂/KOH leads to potassium salts of 2-{[(1-benzyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy]methyl}hydrazine-1-carbothioamide and 2-{2-[(1-benzyl-6-oxo-1,6-dihydropyridazin-3-yl)oxy]acetyl}hydrazine-1-carbodithioic acid, respectively. Acid hydrolysis of the latter affords 2-benzyl-6-[(5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)methoxy]pyridazin-3(2H)-one.

A novel one-pot 1,3-dipolar cycloaddition/oxidation reaction of 1,4-quinones, aromatic aldehydes, and N-substituted amino esters to construct polysubstituted benzo[f]isoindole-4,9-diones induced by benzoic acid is reported. Based on optimized reaction conditions, various polysubstituted benzo[f]isoindole-4,9-diones derivatives are obtained in moderate yields. This straightforward methodology employs mild reaction conditions, a green oxidant, and readily available starting materials. Notably, a wide range of substrates is tolerated.

Mauveine chromophores and a family of phenosafranins have been extracted from the Colour Experience Museum black precipitate with boiling ethanol and separated by chromatography. Phenosafranin (287.1295), monomethylphenylsafranin (301.1452) and a dimethylphenosafranin (315.1609) were observed. Tentative evidence for small quantities of N-tert-butylmauveine A and N-tert-butylmauveine B has been found by comparison of the data to standard retention times and accurate mass data. A synthetic method which reproduces the composition of mauveine extracted from the black precipitate, which is rich in mauveine A, is described.

An improved process for the synthesis of YG-056SP, a potent oxazolidinone candidate against multi-drug resistant bacteria, is developed. Compared with the original synthetic route, this new approach is two steps shorter, and all of the steps involve simple purifications without column chromatography. More importantly, it avoids the use of explosive azide compounds and expensive metal catalysts. The new reaction conditions are mild and safe, which is more suitable for the scalable synthesis of YG-056SP for preclinical studies.

A simple strategy to afford trifluoromethyl-containing bendamustine hydrochloride in 34% overall via nine simple steps including substitution, selective reduction, N-acylation, cyclization, esterification, nitro-reduction, N-dihydroxyethylation, chlorination, and acid-catalyzed hydrolysis from commercially available 2,4-dinitrochlorobenzene is described. The structures of the intermediates and target product are established on the basis of infrared, nuclear magnetic resonance, and high resolution mass spectrometer. Moreover, the structure of target product is also confirmed by X-ray crystal analysis, and further studies indicate that the existence of intermolecular O–H···Cl and N–H···Cl hydrogen bonds are effective in stabilization of the crystal structure.

Rh(III)-catalyzed C–H activation of salicylaldehyde followed by an insertion reaction with sulfoxonium ylides and cyclization is applied to the synthesis of flavonoids. This one-pot strategy exhibits good functional group tolerance and gives flavones in moderate-to-good yields.

Two sets of novel indole-based thiosemicarbazone systems 8a–d and 9a–d are prepared by the Schiff base condensation reaction of indole carbaldehydes 4 and 6 with a range of thiosemicarbazides 7a–d in high yields and purity. The antioxidant properties of the synthesised compounds 8a–d and 9a–d are determined by employing three different assays, namely 2,2-diphenyl-1-picrylhydrazyl hydrate–free radical scavenging, ABTS [2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] cationic radical decolarization and cupric ion reducing antioxidant capacity. The anticholinesterase properties of the products are investigated by acetylcholinesterase and butyrylcholinesterase enzyme inhibition assays. The methyl-substituted compounds 8b and 9b display the highest inhibition for the ABTS assay and absorbance values for the cupric ion reducing antioxidant capacity assay, while compound 9c shows the best activity for 2,2-diphenyl-1-picrylhydrazyl hydrate assay. Moderate inhibition of acetylcholinesterase and butyrylcholinesterase is determined in the case of compound 8b.

A simple and efficient one-pot multicomponent approach for the synthesis of tertiary arylamines bearing N,N-bis(isoxazol-5-yl)methyl groups is developed through reactions including sequential diprop-3-ynylation of primary amines with propargyl bromide in the presence of calcium hydride in N,N-dimethylformamide, and 1,3-dipolar cycloaddition with nitrile oxides generated in situ from hydroximyl chlorides in DMF-Et₃N. This protocol provides advantages such as high regioselectivity, easy operation, and moderate-to-good product yields with a wide substrate scope under mild conditions.

Cucurbit[8]uril (Q[8]) was used as the building block for the facile preparation of Q[8]-based supramolecular assemblies in aqueous HCl solutions (A). The Q[8]-based supramolecular assembly was constructed of Q[8] molecules held together through outer surface interactions of cucurbit[n]urils, and hydrogen bonding between latticed water molecules and portal carbonyl oxygens of Q[8]. The porous structure resulted in different adsorption properties for different fluorophore guests (FGs), including dyes and fused-ring compounds, and fluorescence enhancement or colour changes resulted in luminescent materials (FG@As). Moreover, some of the FG@A systems could selectively respond to certain volatile organic compounds, for which they can be used as solid sensors.

Selective aerobic oxidation of α-pinene to high-value products is a major challenge in chemistry. Metalloporphyrins are proved to be selective catalysts for aerobic oxidation of simple hydrocarbons. Herein, we extend this method to more complex substrates using metallodeuteroporphyrins as model catalysts. It was found that the oxidation occurs mainly on the C=C and allylic C–H bonds of α-pinene influenced by the reaction temperature, reaction time, catalyst concentration, and oxygen flow rate. Allylic C–H oxidation products are obtained with a maximum selectivity value of 78.4% using the following reaction conditions: 105°C, 7 h, 5 ppm, and 60 mL/min. The influence of the metal nuclei of the metallodeuteroporphyrins on this reaction is also investigated. It was found that metallodeuteroporphyrins with Fe³⁺ as the metal nucleus exhibit the highest catalytic activity.

A new hydrazone-based colorimetric Cu²⁺ chemosensor is synthesized. Its structure was confirmed by single-crystal X-ray diffraction. Its binding properties towards various metal ions are examined through absorption spectroscopy. In aqueous THF solution, the chemosensor exhibits selective recognition towards Cu²⁺ over other metal ions with a colour change from colourless to pink. The complex formed between the chemosensor and Cu²⁺ ions forms a 2:1 stoichiometry with an association constant of 2.46 × 10⁸M⁻². The analytical detection limit for Cu²⁺ by the naked eye is as low as 10.0 μM.

An efficient method is developed for the synthesis of 4-(3-arylprop-2-ynyloxy)-6-methyl-2-(methylthio)pyrimidines via palladium-catalyzed Sonogashira reactions of 4-methyl-2-(methylthio)-6-(prop-2-yn-1-yloxy)pyrimidine with electron-poor aryl iodides in acetonitrile at room temperature. Excellent yields of the products were obtained in reaction times of 9–11 h.

A series of bimetallic dppfM(II) (dppf = 1,1’-bis (diphenyphosphino) ferrocene; M = Pt and Pd) dithiocarbamate complexes is synthesized and characterized by spectroscopic methods and single-crystal X-ray diffraction. Their antitumor activities in vitro are investigated by MTT assays against four cancer cell lines. The anticancer studies indicate most of the complexes display good to excellent antitumor activity. Remarkably, the platinum complex with a pyrrolidinyl substituent (3b) was identified as the most promising candidate due to its high potency and broad spectrum of activity.