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A protocol for synthesizing triazole-containing pyrazolines and pyrazoles selectively using trifluoromethylated 5-(1,2,3-triazol-1-yl)enones as starting materials, is reported. The selectivity of the reaction was controlled by the nature of the hydrazine or derivative used: free hydrazines furnished the 1,5-regiosiomer exclusively in yields up to 98%, whereas protected hydrazines provided the 1,3-regioisomer in yields up to 77%. To demonstrate the synthetic versatility of the triazole-based enone, reactions with other unsymmetrical dinucleophiles (hydroxylamine hydrochloride and S-methyl isothiourea sulfates) allowed the selective preparation of triazole-containing isoxazoline and pyrimidine rings.

In this work, the reactivity of 5-bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one toward primary aliphatic amines was studied. The reaction was found to be extremely selective to synthesize a series of 1-alkyl-4-(aminoalkyl)-2-(trifluoromethyl)-1H-pyrroles (13 examples, up to 90% yield) and a series of highly functionalized β-enaminones (6 examples, up to 78% yield), with only the amount of amine and the reaction conditions needing to be controlled. The structure of the products was unambiguously determined by single crystal X-ray diffraction and 2D NMR experiments.

This paper covers the synthesis of a series of eleven examples of new 7-(1H-pyrrol-1-yl)spiro[chromeno[4,3-b]quinoline-6,1′-cycloalkanes] (3), where cycloalkanes are cyclopentane, cyclohexane, and cycloheptane. Heterocyclic system 3 was successfully obtained in 53–78% yields by the Clauson–Kaas reaction, in which 7-amino-spiro[chromeno[4,3-b]quinoline-6,1′-cycloalkanes] (1) were reacted with 2,5-dimethoxytetrahydrofuran (2) in an acetic acid medium at 90 °C for 48 h. Then, to demonstrate synthetic applicability, the 9-bromoquinoline-substituted derivative 3h was selected and successfully employed in traditional CC and CN cross-coupling reactions, yielding three new modified tacrine scaffolds (4–6). Photophysical studies of π → π* and n → π* transitions corroborated the aromatic structures of the heterocycle molecules and showed high emission properties, good Φf values, and moderate to large Stokes shifts (SS).

The present work reports the biological assays between synthetic BF2-naphtyridine complexes and four proteins: human serum albumin (HSA), calf-thymus DNA (CT-DNA), tyrosinase and acetylcholinesterase enzymes via spectroscopic analysis at physiological conditions, combined with molecular docking simulations. The BF2-complexes presented spontaneous and moderate binding ability to HSA through the ground-state association (static fluorescence quenching mechanism). The main binding site is Sudlow's site I (subdomain IIA) and the binding does not perturb significantly both secondary and surface structure of HSA. Despite BF2-complexes showed good binding ability with HSA, these compounds presented weak intercalative ability with CT-DNA (the most conventional and simple model to preliminary studies), except in the case of 1 h, which suggested that the presence of electronic donor groups in both aromatic ring moieties of BF2-complex structure can increase the intercalative ability for DNA strands. Competitive binding displacement assays in the presence of methyl green and molecular docking calculations indicated that the studied compounds interact preferentially in the major groove of DNA. In addition, the assayed compounds presented the ability to activate or inhibit both tyrosinase (the decontrolled activity can induce melanoma carcinoma) or AChE (involved in reactions related to the function of neurotransmitters) enzymes.

The regioselective synthesis of twenty novel [3-substituted 5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl][6-aryl-(2-methylthio)pyrimidin-4-yl]methanones from the cyclocondensation reactions of new 6-aryl-2-(methylthio)pyrimidine-4-carbohydrazides with 4-substituted 1,1,1-trifluorobut-3-en-2-ones is reported. Human acetylcholinesterase (HsAChE) and butyrylcholinesterase (HsBChE) inhibition tests were performed on selected products in order to explore the possible pharmacological applications of these compounds. Two compounds showed significant and selective inhibitory activity for BChE.

The 1,4-dicarbonyl scaffold ethyl 3-formyl-4,5-dihydrofuran-2-carboxylate was obtained through the rearrangement of the parent ethyl 2-(4,5-dihydrofuran-3-yl)-2-oxoacetate and applied to the synthesis of a series of 7-alkoxy-2,3-dihydrofuro[2,3-d]pyridazines. Twelve pyridazines­ were obtained in yields of up to 70%.

5-Bromo- and 5,5-dibromo-1,1,1-trihalo-4-methoxypent-3-en-2-ones (brominated enones) have proven to be attractive building blocks for the construction of heterocyclic and polyheterocyclic compounds bearing a trihalomethyl moiety through interesting cyclocondensation, alkylation, and cycloaddition reactions. This review compiles all of the reactions conducted with these brominated enones since they were first disclosed in 2001.1 Introduction2 Synthesis and Initial Applications3 Synthesis Using First-Generation Intermediates4 Synthesis Using Second-Generation Intermediates5 Synthesis Using Third-Generation Intermediates6 Conclusions

The crystallization mechanisms of a series of fourteen 7-chloro-4-substituted-quinolines (substituents: (1) OCH3, (2) OCH2CH3, (3) OCH2CHCH2, (4) O(CH2)2OH, (5) O(CH2)3OH, (6) NH(CH2)2CH3, (7) NH(CH2)3CH3, (8) NH(CH2)2OH, (9) NHCH(CH2CH3)CH2OH, (10) NH(CH2)2Cl, (11) NHNCH(C6H5), (12) NHNCH(2-FC6H4), (13) NHNCH(3-FC6H4), and (14) NHNCH(4-FC6H4)) were proposed based on a retrocrystallization approach using the supramolecular cluster as demarcation. Crystallization mechanism stage parameters – NCG% and NG/NC – were determined. The 4-substituents present in quinolines caused six different mechanisms, starting from the monomers in solution to dimers, 1D nuclei, and 2D nuclei (6, 11, 12); 2D nucleus formation (5); 1D nuclei to 2D nuclei (7, 9); concomitant dimers and 1D nuclei to a 3D crystal (8); 1D nuclei directly to a 3D crystal lattice (1–4, 10, 14), and dimers to 2D nuclei and then to a 3D crystal (13). Analysis of GAI showed atom⋯atom intermolecular interactions in the proposed first nuclei for compounds 4 and 5. The nucleation process inferred in the solid state was partially confirmed during the formation of the proto-crystal in solution due to the changes of the hydrogen chemical shift in variable-concentration 1H-NMR experiments. Results revealed that the size of the alkyl chain and the presence of different functional groups in the 4-substituents influenced the crystallization process.

Graphical abstract, Highlights • Ultrasound is a powerful tool in the synthesis of pyrimidines. • Selectivity in the synthesis of pyrimidines under ultrasound is demonstrated. • Synergic effects of US combined with other methods are presented., The pyrimidine scaffold is present in many bioactive drugs; therefore, efficient synthetic routes that provide shorter reaction times, higher yields, and site-selective reactions are constantly being sought. Ultrasound (US) irradiation has emerged as an alternative energy source in the synthesis of these heterocyclic scaffolds, and over the last ten years there has been a significant increase in the number of publications mentioning US in either the construction or derivatization of the pyrimidine core. This review presents a detailed summary (with 140 references) of the effects of US (synergic or not) on the construction and derivatization of the pyrimidine core through classical reactions (e.g., multicomponent, cyclocondensation, cycloaddition, and alkylation reactions). The main points that were taken into consideration are as follows: chemo- and regioselectivity issues, and the results of conventional heating methods compared to US and mechanistic insights that are also presented and discussed for key reactions.

A new series of ten examples of Schiff bases, namely (E)-2-(((2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenols 3, was easily synthesized with yields of up to 91% from the reactions involving a series of 2-(R-substituted) 6-amino-4-(trifluoromethyl)quinolines 1 and 4(5)-R1-substituted salicylaldehydes 2 – in which alkyl/aryl/heteroaryl for 2-R-substituents are Me, Ph, 4-MeC6H4, 4-FC6H4, 4-NO2C6H4, and 2-furyl, and R1-substituents are 5-NEt2, 5-OCH3, 4-Br, and 4-NO2. Complementarily, the Schiff bases showed low to good quantum fluorescence yield values in CHCl3 (Φf = 0.12–0.80), DMSO (Φf = 0.20–0.75) and MeOH (Φf = 0.13–0.85). Higher values of Stokes shifts (SS) were observed in more polar solvents (DMSO; 65–150 nm and MeOH; 65–130 nm) than in CHCl3 (59–85 nm). Compounds 3 presented good stability under white-LED irradiation conditions and moderate ROS generation properties were observed.

Herein, we explore the synthetic potential of tetrazolo[1,5-a]pyrimidines to obtain new pyrimidine derivatives by click chemistry and hydrogenation. Click chemistry reactions of the trifluoromethyltetrazolo[1,5-a]pyrimidines with terminal acetylenes produced unprecedented trifluoromethylated triazolylpyrimidines in excellent yields (84-98 %) in which one of them was active against all tested microorganisms, presenting moderate MIC values (62.5-15.62 mg/ml). Hydrogenation was carried out using Pd/C-H2 in MeOH under conventional, photochemical, and pressure (5 bar) conditions. The hydrogenation was an excellent method to obtain 2-amino-6-aryl-4-trifluoromethyl pyrimidines and/or 2-amino-6-aryl-4-trifluoro methyltetrahydro pyrimidines with a preference for 2-aminopyrimidine formation. The photochemical hydrogenation was the fastest and only pathway to reduce aryl-brominated substrate for the product without dehalogenation. Trifluoromethyl-substituted tetrazolo[1,5-a]pyrimidines reacted to 2-amino-6-aryl-4-trifluoromethyl pyrimidine formation in preference to the formation of the corresponding tethaydropyrimidines. However, the hydrogenation of non-trifluoromethylated tetrazolo[1,5-a]pyrimidines showed a preference for tetrahydropyrimidine formation.

A series of seven 5-aryl-1-(1,1-dimethylethyl)-3-trifluoromethyl-1H-pyrazoles [in which aryl: C6H5 (1); C6H4-4-F (2); C6H4-4-Cl (3); C6H4-4-Br (4); C6H4-4-I (5); C6H4-4-CH3 (6), C6H4-4-OCH3 (7)] and 5-aryl-1-(1,1-dimethylethyl)-1H-pyrazole [C6H4-4-NO2 (8)] was studied at the molecular and supramolecular level. X-ray diffraction, thermal analysis, sublimation enthalpy data, NMR spectroscopy, and DFT calculations were used in this systematic study. The supramolecular cluster was used as demarcation and furnished energetic and contact area data of each compound, which allowed proposals of crystallization mechanisms. Two different mechanisms were observed: (i) compounds 1–4 had 2 stages, where initially the monomers formed a 2-D block, followed by the formation of the 3-D block; (ii) compounds 5–8 also had 2 stages, where initially the monomers formed a 1-D block, followed by formation of the 3-D block. The packing observed in the crystal was corroborated by data from 1H NMR experiments. The types of interactions observed were evaluated using Hirshfeld surface and QTAIM analysis and showed slight differences in both methods. Lastly, energetic and topologic data obtained from the clusters were correlated with crystal properties such as crystal packing efficiency, sphericity, and sublimation enthalpy and presented good trends between data.

The synthetic potential of 5-bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one toward the catalyst-free synthesis of N-pyrrolyl(furanyl)-piperazines, 1,4-diazepanes, and 1,4-diazocanes through a telescoped protocol is reported. This three-component one-pot method provided 23 examples with high chemo- and regioselectivity at yields up to 96%.

This paper describes the synthesis of a novel series of 2-aryl-6-(1H-indol-1-yl)-4-(trifluoromethyl)quinolines, in which aryl = C6H5, 4-CH3C6H4, 4-FC6H4, 4-CF3C6H4 and heteroaryl = 2-thienyl, by an Ullmann-type cooper-catalyzed amination cross-coupling reaction. Photophysical properties of indolyl-quinolines were investigated using absorption and emission analysis. The emission fluorescence analysis showed a blue to cyan region emission in the 400–650 nm range. Large Stokes shifts values were observed for all new quinolines and attributed to the ICT state and to the electron-substituent properties. The ability to generate 1O2 species after being exposed to white light and biomolecule-binding DNA / HSA properties were also investigated.

An efficient protocol for the assembly of a new series of 1,3-disubstituted 4,5-bis(trifluoromethyl)-1H-pyrazoles – through a concise sequential iodination-trifluoromethylation reaction at the C-4 position of an initial series of 1-aryl-3-(alkyl/aryl)-5-trifluoromethyl-1H-pyrazoles (electronically deactivated heterocycles), using NIS and MFSDA, at good conversion yields and in short reaction times – is reported.

The use of β-enamino diketones as an easy entry to the regioselective synthesis of [1,2,4]triazolo[1,5-a]pyrimidines is reported. These ketones reacted with 3-amino-1H-1,2,4-triazoles to furnish exclusively 6-substituted 5-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidines in yields of up to 95%. The regioselectivity of the reactions performed was maintained regardless of the substituent in the starting ketone or aminoazole.

This paper presents a new family of pyrimidine-based BF2 complexes. The series contains six examples of 1,1-difluoro-3-aryl(heteroaryl)-1H-pyrimido[1,2-c][1,3,5,2]oxadiazaborinin-9-ium-1-uides (2) — in which aryl(heteroaryl) = phenyl, 4-MeC6H4, 4-N(CH3)2C6H4, 4-NO2C6H4, 2-naphthyl, and 2-thienyl. The heterocycles 2 were easily synthesized at yields of 50–68% from reactions — at room temperature for 24 h — of simple N-(pyrimidin-2-yl)benzamides (1) with BF3·Et2O, and they were fully characterized by 1H-, 13C-, 19F, 11B-NMR, GC–MS, and X-ray diffractometry. Moreover, the photophysical properties, TD-DFT analysis, BSA-binding experiments, and molecular docking studies for the new organoboron complexes 2 were determined, presented, discussed, and compared with similar compounds that have already been described.

The synthesis and structural elucidation of a new series of six 6-amino-2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl) quinolines are reported, yielding 22 to 87% isolated products. This was achieved through a regioselective intramolecular cyclization reaction of novel (Z)-4-((4-aminophenyl)amino)-1,1,1-trifluoro-but-3-en-2-ones in an acidic solvent-free medium, in which alkyl/aryl/heteroaryl = methyl, phenyl, 4-MeC6H4, 4-FC6H4, 4-NO2C6H4, and 2-furyl. The novel compounds were fully characterized by 1H-, 13C- and 19F-NMR spectroscopy, GC-MS and single-crystal X-ray diffraction. In addition, the preliminary investigation of photophysical properties of the 6-aminoquinolines (UV-Vis, fluorescence, quantum yield calculations, Stokes shifts, and TD-DFT analysis) and inhibitory activity against M. tuberculosis H37Rv strain was also presented. Thermal analyses were carried out to assess their properties as new materials.

Deep eutectic solvents (DES) have been used as sustainable media for the synthesis of more efficient nanoparticle-based catalysts. However, the effects of DES deposition on the catalytic activity of metal oxide nanoparticles like TiO2 are unknown. Thus, the goal of this study was to facilitate the deposition of DES onto TiO2 surfaces and investigate how this coating modulates the catalytic activity of TiO2 in the photodecomposition of organic dyes. Results for the thermal and spectroscopic properties of the TiO2 coated with DES in relation to pure materials indicated interactions between these two materials, confirming the deposition of DES onto the TiO2 surface. Different choline chloride : HBD molar ratios had little impact on the thermal stability, phase transitions, crystallization and amorphization of the mixture. In general, the catalytic activity of TiO2 coated with DES was reduced. However, TiO2 covered with ChCl : malonic acid (1 : 2) showed the best catalytic activity and it was better as greater the amount of DES used in the surface deposition.

Reaction of 5-bromo enones with pyrazoles provided a series of unexpected N,O-aminal derivatives, through a 1,4-conjugated addition at the β-carbon of the 5-bromo enones instead of the expected nucleophilic substitution of the bromine. This reaction also furnished the 1,3-regioisomer of the pyrazole. A similar reaction of pyrazoles using 5-bromo enaminones furnished only N-alkylated pyrazoles-with high regioselectivity and at good yields-through nucleophilic substitution of the bromine.

A new series of ten examples of (E)-2-(((2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenols (Schiff bases), was easy synthesized at yields of up to 91% from the reactions between a series of 2-(R-substituted) 6-amino-4-(trifluoromethyl)quinolines and 4(5)-R1-substituted salicylaldehydes – in which alkyl/aryl/heteroaryl for 2-(R)-substituents are Me, Ph, 4-MeC6H4, 4-FC6H4, 4-NO2C6H4, and 2-furyl, and (R1)-substituents are 5-NEt2, 5-OCH3, 4-Br, and 4-NO2. The compounds are fully characterized by 1H-, 13C-, and 19F-NMR spectroscopy and SC-XRD. Complementarily, the photophysical, photostability, and reactive oxygen species (ROS) generation properties of these novel trifluoromethylated Schiff bases are evaluated.

The synthesis, antimicrobial activity evaluations, biomolecule-binding properties (DNA), and absorption The synthesis, antimicrobial activity evaluations, biomolecule-binding properties (DNA), and absorption and emission properties of a new series of (Z)-1,1,1-trichloro-4-alkyl(aryl)amino-4-arylbut-3-en-2-ones (4,5) and 2,2-difluoro-3-alkyl(aryl)amino-4-aryl-6-(trichloromethyl)-2H-1,3,2-oxazaborinin-3-ium-2-uides (6,7) in which 3(4)-alkyl(aryl) = H, Me, iso-propyl, n-butyl, C6H5, 4-CH3C6H4, 4-CH3OC6H4, 4-NO2C6H4, 4-FC6H4, 4-BrC6H4, 2-naphthyl, is reported. A series of β-enaminoketones (4,5) is synthesized from the O,N-exchange reaction of some amines (3) with (Z)-1,1,1-trichloro-4-methoxy-4-aryl-but-3-en-2-ones (1,2) at 61–90% yields. Subsequently, reactions of the resulting β-enaminoketones with an appropriate source of boron (BF3.OEt2) gave the corresponding oxazaborinine derivatives (6,7) at 50-91% yields. UV-Vis and emission properties of biomolecule-binding properties for the DNA of these new BF2-β-enamino containing CCl3 units were also evaluated. Some compounds from the present series also exhibited potent antimicrobial effects on various pathogenic microorganisms at concentrations below those that showed cytotoxic effects. Compounds 4d, 4e, 6e, and 6f showed the best results and are very significant against P. zopfii, which causes diseases in humans and animals.

A series of seven N-phenylamides [R–C(O)NHPh, in which R: CH3, C(CH3)3, Ph, CF3, CCl3, CBr3, and H] were used as models in this study. Molecular packing and intermolecular interactions were evaluated by theoretical calculations, solution NMR, and quantum theory of atoms in molecules analyses. Crystallization mechanisms were proposed based on the energetic and topological parameters using the supramolecular cluster as demarcation. Concentration-dependent 1H NMR experiments corroborated the proposed interactions between molecules. For all compounds (except for R: H, which initially formed tetramers), layers (two-dimensional) or chains (one-dimensional) were formed in the first stage of the proposed crystallization mechanisms. The presence of strong intermolecular NH···O═C interactions promoted the first stages. The study in solution provided different values of association constant (Kass) governed by the hydrogen bond NH···O═C, showing that the stronger interactions are directly influenced by the substituen...

The synthetic versatility of 4-alkoxy-4-alkyl/aryl-1,1,1-trichloroalk-3-en-2-ones (enones) for the synthesis of [1,2,4]triazolo[1,5-a]pyrimidines, in which the trichloromethyl group is either maintained or eliminated from the product by simply controlling the reaction medium, is reported. These enones react with 3-amino-1H-1,2,4-triazoles under acidic conditions to furnish exclusively 7-(trichloromethyl)-[1,2,4]triazolo[1,5-a]pyrimidines, whereas under basic conditions [1,2,4]triazolo[1,5-a]pyrimidin-5/7(1H)-ones are obtained with elimination of the trichloromethyl group. The regioselectivity of the reactions performed under basic conditions is highly influenced by the substituents present in the starting enones. Twenty-one examples are synthesized using these two methodologies, with yields of up to 86%.

The present paper describes first an efficient methodology for an easy O -functionalization (alkylation) of tetracyclic hydroxyisoxazolines 1 applied to the synthesis of eight examples of new 3-(alkoxy)-3-(trifluoromethyl)-3,3a-dihydrospiro[chromeno [4,3- c ]isoxazole-4,1′-cycloalkanes] ( 6-9 ) at 61–84% yields, in which the alkoxy substituents were methoxy, benzyloxy, allyloxy, or prop-2-yn-1-yloxy; while the cycloalkanes were 5-, 6-, and 7-membered carbocycles, as well as 4′-methyl- and 4′- t -butyl-cyclohexane. The reaction medium used 1 , four alkyl halides ( 2 - 5 ), K 2 CO 3 , and KI in DMF at room temperature. The selected 3-(prop-2-yn-1-yloxy)-substituted isoxazolines 6 were successfully used as a CC -fragment in the construction of another series of five examples of 3-((1-benzyl-1 H -1,2,3-triazol-4-yl)methoxy)-3-(trifluoromethyl)-3,3a-dihydrospiro[chromeno[4,3- c ]isoxazole-4,1′-cycloalkanes] ( 10 ), at 36–84% yields, through a regioselective 1,3 dipolar cycloaddition reaction catalyzed by copper iodide (CuAAC), using benzyl azide as an NNN -building block (Click Chemistry).

The structure of four spiro[chromeno[4,3-b]quinoline-6,1′-cycloalkan]-7-amine (1–4) was determined by X-ray diffraction methods. The quinoline rings were obtained as almost planar structures, with an RMS deviation within a range of 0.0345–0.0641 A, while the chromene rings are not planar. Moreover, the cycloalkane rings are attached to the chromene in spiro form. Three of the four compounds crystallize as solvates—one with ethanol and the other two with water. The crystal packing for compounds 1–4 is discussed in terms of intermolecular interactions, and it is shown that the crystal packing of these heterocycles is governed by: strong O–H···N and N–H···O hydrogen bonds; weak C–H···O and C–H···N hydrogen bonds; and very weak C–H···Cl, C–H···Br, and C–H···π interactions. Also, π···π and lone pair···π interactions are present in the crystal packing of the heterocycles. These interactions lead to the formation of endless chains along a plane, as well as supramolecular dimers and the arrangement of molecules in layers. Additionally, UV–Vis absorption spectra properties are also discussed. The structure of four spiro[chromeno[4,3-b]quinoline-6,1’-cycloalkan]-7-amines are determined by single crystal X-ray diffraction. The crystal packing is discussed in terms of intermolecular interactions (strong O–H···N and N–H···O hydrogen bonds; weak C–H···O and C–H···N hydrogen bonds; and very weak C–H···Cl, C–H···Br, and C–H···π interactions). Also, π···π and lone pair π interactions are present in the crystal packing of the heterocycles.

This study reports a comparison between conventional methods, ionic liquids, microwave (MW) irradiation, and combinations thereof for the synthesis of a series of fourteen 1-aryl-2-arylamino-5-trifluoroacetyl-1,2,3,4-tetrahydropyridines. In all of the reactions tested, the products were obtained at very good yields (87–97%), but the reaction times were very different, depending on the method used. Comparing to other methods, the time decreased to 1 min when [BMIM]BF 4 under MW irradiation was used, thus evidencing a synergic effect.

Electrospray ionization mass spectrometry with variable collision-induced dissociation (CID) was used to conduct a comprehensive study of cation-anion interaction strength in dicationic ionic liquids (ILs). This investigation reports the influence of anion structure (Cl−, Br−, NO3−, BF4−, and SCN−) and spacer chain length (n = 4, 6, 8, and 10) on the interaction strength of dicationic ILs derived from 1,n-bis(3-methylimidazolim-1-yl)alkane. The anion-cation interaction strength was determined from the binary mixture of ILs and from the center-of-mass energy (Ecm). Moreover, two novel models were proposed, based on the extended first order and zero order equations, which allow determining the order of stability from the constant dissociation (Kd) and decay rate (k0), respectively. Additionally, quantum chemical calculations of cation-anion energy were done in order to support experimental results. The order of energy of the anion-cation interaction determined by both Ecm,1/2 and Kd followed the same trend, while the order of the cation-anion interaction strength observed in the binary mixtures was in accordance with quantum chemical calculations. The model based on zero order process did not show good agreement with either the Ecm,1/2 or Kd, thus indicating that it is a very simplified model that does not result in an appropriate order for the cation-anion energy interaction. Orders were not comparable; however, it was the first time that binary mixture experiments and Ecm were used with the same set of ILs.

This paper firstly describes the synthesis of a series of (Z)-4-((3-chloro-4-fluorophenyl)amino)-1,1,1-trifluorobut-3-en-2-ones (3a–f) as well as 1-(1-((3-chloro-4-fluorophenyl)amino)-3,4-dihydronaphthalen-2-yl)-2,2,2-trifluoroethanone (3g), from the O,N-exchange reaction of some 4-methoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones (1) with 3-chloro-4-fluoroaniline (2), at 70–90% yields. Subsequently, in concentrated sulfuric acid, the enaminoketones 3 underwent a successful and regioselective intramolecular cyclocondensation reaction, which furnished a novel series of 2-alkyl(aryl)-7-chloro-6-fluoro-4-(trifluoromethyl)-quinolines (4) at 70–85% yields. To demonstrate synthetic applicability through the Sonogashira coupling reaction for obtaining quinolines with potential antimicrobial activity, the synthesis of a novel series of 2-alkyl(aryl)-6-fluoro-7-(phenylethynyl)-4-(trifluoromethyl)-quinolines (5) was performed, using quinolines 4 and phenylacetylene, via a regioselective Sonogashira coupling reaction (25–50% yield). Unfortunately, the new series of heterocycles 4 and 5 did not produce significant results against bacteria and fungi at the concentrations of 80–0.31 μg/mL.

This paper reports the results of the synthesis and structural elucidation by multinuclear NMR spectroscopy and single crystal X-ray diffraction of a new series of four examples of 1,1-difluoro-3-methyl-9-(aryl/heteroaryl)-7-(trifluoromethyl)-1H-[1,3,5,2]oxadiazaborinino[3,4-a][1,8]naphthyridin-11-ium-1-uides, which were obtained, at good yields (60–66%), from the reaction of 7-substituted N-(5-(trifluoromethyl)-1,8-naphthyridin-2-yl)acetamides — in which the 7-substituents are C6H5, 4-CH3C6H4, 4-FC6H4, and 2-Thienyl — with BF3·Et2O solution. One-dimensional multinuclear NMR spectroscopy (1H, 13C, 19F, and 11B) and two-dimensional 1H–15N HMBC are presented as powerful tools for an easy and secure NMR chemical shift assignments and structural characterization of fluorinated 1,8-naphthyridine-based boron complexes. Additionally, investigations of photophysical, electrochemical and DNA-binding properties were done.

This work reports a successful synthesis of two new series of 2-(aryl/heteroaryl)-6-(morpholin-4-yl/pyrrolidin-1-yl)-(4-trifluoromethyl)quinolines via the Buchwald–Hartwig amination, at 60–88% yields, starting from 2-(aryl/heteroaryl)-6-bromo-4-trifluoromethyl-quinolines and heteroarylamines (morpholine and pyrrolidine). The 6-bromoquinoline precursors were obtained from an easy intramolecular cyclization reaction of (Z)-4-((4-bromophenyl)amino)-1,1,1-trifluoro-but-3-en-2-ones, which were previously prepared through the reaction of 4-methoxy-(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones with 4-bromoaniline. Photophysical analyses indicated intraligand and charge-transfer type transitions, in agreement with the aromatic structures of the heterocycle moieties. In the case of ct-DNA titrations (via the absorption and emission method), morpholinyl- and pyrrolydinyl-substituted quinolines had strong interactions with ct-DNA, which could be attributed to π-stacking and/or hydrogen-bonding interactions.

A series of 5(3)-aryl-3(5)-carboxyethyl-1-tert-butylpyrazoles (aryl, 4-X-C6H4, where X = H, F, Cl and Br) were studied in the solid state. The 1,3-regioisomers (carboxyethyl group in 3-position) of t-butylpyrazoles crystalized in three different forms: s-cis, s-trans or s-cis + s-trans. On the other hand, the 1,5-regioisomers (carboxyethyl group in 5-position) of t-butylpyrazoles showed only s-trans conformation. The 13C CPMAS and SCXRD data confirmed that each 1,3- and 1,5-regioisomers of t-butylpyrazoles crystallized only one of the three mentioned forms. The potential energy surface (PES) yielded insights regarding the formation of each conformer. In general, quantum mechanical calculations showed that the conformer s-trans is more stable than s-cis, and the calculated stability difference was 0.7 kcal mol−1 for the 1,3-regioisomers and 3.5 kcal mol−1 for the 1,5-regioisomers. Moreover, 1,5-regioisomers of t-butylpyrazoles showed intramolecular interactions of type CH⋯OC between the carbonyl and t-butyl group, which was obtained by QTAIM analysis. This interaction can influence the stabilization for s-trans conformation in the solid state. In contrast, the 1,3-regioisomers did not show intramolecular interaction with the COOEt group, and the conformation adopted in the solid state should be the consequence of the crystalline packing. The QTAIM analysis of the more stable dimers of s-trans-conformation for X = Cl, Br showed that the halogen atoms interact with the COOEt group, helping stabilize this conformation. On the other hand, in the s-cis⋯s-cis conformation dimer (X = Cl, Br), the COOEt group was stabilized by the phenyl group, which is the same stabilization for X = H.

This paper presents a series of six examples of 1,1-difluoro-3-aryl(heteroaryl)-1H-pyrido[1,2-c][1,3,5,2]oxadiazaborinin-9-ium-1-uides (2)—in which aryl(heteroaryl) = phenyl, 4-MeC6H4, 4-N(CH3)2C6H4, 4-NO2C6H4, 2-naphthyl, and 2-thienyl—as pyridine-based boron heterocycles with variable ligand structures. The heterocycles 2 were easily synthesized at yields of 51–70% from reactions—at room temperature for 24 h—of simple N-(pyridin-2-yl)benzamides (1) with BF3·Et2O, and they were fully characterized by 1H-, 13C-, 19F-, and 11B-NMR spectroscopy, GC-MS, and X-ray diffractometry. The optical and electrochemical properties of 2 (UV-vis spectra, fluorescence spectra, quantum yield calculations, Stokes’ shifts, redox potentials, and DFT calculations) were determined and discussed. BSA-binding experiments and molecular docking studies of new complexes 2 were performed and correlated between each other.

A series of seven novel scaffolds of 2-substituted 4-trifluoromehyl-5H-chromeno[4,3-b]pyridin-5-ones (3a-g), where R (2-substituents) = Me, Ph, 4-tolyl, 4-NO2C6H4, 4-FC6H4, 4-BrC6H4, and 2-thienyl, were easily and regioselectively synthesized by employing a [3 + 3] cyclocondensation reaction of 4-methyl(aryl/thienyl)-4‑methoxy-1,1,1-trifluoroalk-3-en-2-ones (1) with 4-aminocoumarin (2) in up to 66% yields. The photophysical and electrochemical analysis of 3a-g revealed large Stokes shifts (30 to 130 nm) due to the ICT state and low redox oxidation processes. Additionally, the antioxidant activity evaluated by DPPH assays (aided by cyclic voltammetry) showed that compounds 3b (R = Ph, EC50 (µM) = 19.6) and 3e (R = 4-FC6H4, EC50 (µM) = 19.1) had the most significant radical scavenging capacity (ref. ascorbic acid = 10.9 µM).

An efficient synthesis methodology for a series of tetrazolo[1,5-a]pyrimidines substituted at the 5- and 7-positions from the cyclocondensation reaction [CCC + NCN] was developed. The NCN corresponds to 5-aminotetrazole and CCC to β-enaminone. Two distinct products were observed in accordance with the β-enaminone substituent. When observed in solution, the compounds can be divided into two groups: (a) precursor compounds with R = CF3 or CCl3, which leads to tetrazolo[1,5-a]pyrimidines in high regioselectivity with R at the 7-position of the heterocyclic ring; and (b) precursor compounds with R = aryl or methyl, which leads to a mixture of compounds, tetrazolo[1,5-a] pyrimidines (R in the 5-position of the ring) and 2-azidopyrimidines (R in the 4-position of the ring), which was attributed to an equilibrium of azide–tetrazole. In the solid state, all compounds were found as 2-azidopyrimidines. The regiochemistry of the reaction and the stability of the products are discussed on the basis of the data obtained by density functional theory (DFT) for energetic and molecular orbital (MO) calculations.

The first Quantum Theory of Atoms in Molecules (QTAIM) analysis of [2]rotaxanes was used in combination with quantum mechanical calculations and variable temperature NMR experiments. The study shows all the intramolecular interactions of tetraalkylsuccinamide[2]rotaxanes with different templates. The threads have different stoppers [R1R2NC(O)-CH2CH2-C(O)NR2R1, in which R2/R1 = CH2cy-Hex/CH2Ph, i-Bu, Bu, and Pr]. The different threads used allowed us verify that the contact area between the submolecular components (CMcy···Thr) is closely correlated with the interaction energy (GMcy···Thr) in the [2]rotaxanes studied. Furthermore, the QTAIM data and quantum mechanical calculations confirmed that, in all of the compounds, the hydrogen bonds are responsible for most of the energy from the intramolecular interactions that follow the C–H···π and H···H interactions, independent of the thread used. In the liquid state, using NMR 1H some intramolecular interactions were observed, which is in agreement with the dat...