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A series of ammonium salts was used to propose a step-by-step approach to obtain the stabilization energy and contact area data of supramolecular clusters in charged molecules. A new parameter was presented to assess the cluster energy efficiency.

Crystallization mechanisms were proposed to investigate hydrogen bond and aromatic donor–acceptor interactions in a series of phenyl–perfluorophenyl amides. The modulation of NH⋯OC bonds and aryl complementarity drove a new cocrystal growth.

Quantitative similarity indices (IX) were combined with crystallization mechanism proposals to shed more light on the origins of the supramolecular similarity between a series of benzimidazole derivative structures.

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).

This paper describes the photophysical properties of a series of seven selected examples of 5-(alkyl/aryl/heteroaryl)-2-methyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidines (3), which contain alkyl, aryl, and heteroaryl substituents attached to the scaffolds of 3. Given the electron-donor groups and -withdrawing groups, the optical absorption and emission in the solid state and solution showed interesting results. Absorption UV–Vis and fluorescence properties in several solvents of a pyrazolo[1,5-a]pyrimidines series were investigated, and all derivatives were absorbed in the ultraviolet region despite presenting higher quantum emission fluorescence yields in solution and moderate emission in the solid state. Moreover, the solid-state thermal stability of compounds 3a–g was assessed using thermogravimetric analysis. The thermal decomposition profile showed a single step with almost 100% mass loss for all compounds 3. Additionally, the values of T0.05 are considerably low (72–187 °C), especially for compound 3a (72 °C), indicating low thermal stability for this series of pyrazolo[1,5-a]pyrimidines.

A convenient synthesis of a broad series of thirteen examples of alkyne-spacer derivatives 2 from the well-known Sonogashira cross-coupling reaction on diazenyl-pyrazolo[1,5-a]pyrimidin-2-amine compounds 1 is reported. The reactivity of heterocycles 1 due the presence of selected electron-donor (EDG) and electron-withdrawing (EWG) groups attached to different alkynes was evaluated. Also, the reactional versatility due the position variation of the bromo atom at the scaffolds 1 was also investigated. In general, derivatives presented strong absorption bands at the 250-500 nm optical window and UV to cyan emission properties. Also, the redox analysis was recorded by electrochemical cyclic voltammetry technique. For HSA biomacromolecule assays, spectroscopic studies by UV-Vis, steady-state and time-resolved emission fluorescence, and molecular docking calculations evidenced the ability of each compound to establish interactions with human serum albumin (HSA). Finally, the behavior presented for this new class of heterocycles makes them a promising tool as optical sensors for albumins.

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.

This study reports two strategies for preparing

The selective

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 (E)-2-(((2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenols (Schiff bases), was easy synthesized at yields up to 91% from the reactions involving 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. Complementarily, the Schiff bases showed low to good quantum fluorescence yield values both 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). Also, compounds 3 confirmed to present good stability under white-LED irradiation conditions and moderate ROS generation properties were observed.

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%.

A systematic investigation to assess the degree of similarity between polymorphs was carried out. A similarity indices (IX) approach was applied in ten series of polymorphs with different characteristics and number of molecules in the asymmetric unit. Geometric (ID), contact area (IC), and stabilization energy (IG) parameters were used. It was possible to situate each comparison in different regions of similarity within the polymorphism phenomenon and determine the boundaries between quasi-isostructural polymorphs and polymorphs of low similarity. The multiparameter IDCG index was used as a robust tool to determine the total similarity within the polymorphism phenomenon. The highest contribution of the stabilization energy parameter (45%) toward the final value of similarity (IDCG) was observed, followed by the contact area index (32%). The geometric index contributed approximately 23% to the final value of IDCG. This information reinforces the importance of the contact area and stabilization energy in assessing the degree of similarity between crystalline structures. A new descriptor (IQ) based on the comparison of the energetic contribution of intermolecular interaction types present in each crystal structure is presented. IQ can be a versatile tool and applicable even for systems that do not share any similarity.

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.

The synthesis, antimicrobial activity evaluations, biomolecule-binding properties (DNA), and absorption and emission properties of a new series of (