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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.