Chemistry and properties of fluorescent pyrazole derivatives: an approach to bioimaging applications.

Fluorescent bioimaging is a crucial technique for studies in real cell samples, providing vital information about the metabolism of ions or molecules of biological and pharmaceutical significance. This technique typically uses probes based on organic small-molecule fluorophores, with N-heteroaromatic scaffolds playing an essential role due to their exceptional electronic properties and biocompatibility. Among these, pyrazole derivatives stand out as particularly promising due to their high synthetic versatility and structural diversity.

Microwave-assisted synthesis and functionalization of 2-arylimidazo[1,2-]pyrimidin-5(8)-ones.

Despite the limited applications and scarcity of commercial examples of imidazo[1,2-]pyrimidines, their exceptional properties hold great potential, representing a significant challenge in discovering more critical applications. Herein, we present a microwave-assisted approach for preparing 2-arylimidazo[1,2-]pyrimidin-5(8)-ones and their alkylation and bromination products using easily accessible and inexpensive reagents, thus offering a promising avenue for further search. Notably, the photophysical properties of an -alkyl derivative were investigated, and the results highlight the high potential of these compounds as modular fluorophores.

CsCO-Promoted Alkylation of 3-Cyano-2(1H)-Pyridones: Anticancer Evaluation and Molecular Docking.

Herein, a CsCO-promoted N-alkylation of 3-cyano-2(1H)-pyridones containing alkyl groups with diverse alkyl halides to synthesize N-alkyl-2-pyridones over O-alkylpyridines is reported. The use of alkyl dihalides resulted in complex mixtures of N- and O-alkylated products. The primary factor influencing regioselectivity in these reactions is the electronic effects of substituents on the 2(1H)-pyridone ring, as evidenced by the preferential formation of O-alkylpyridines upon the introduction of aryl groups.

Synthesis of structural analogues of Reversan by ester aminolysis: an access to pyrazolo[1,5-]pyrimidines from chalcones.

Reversan, a multidrug resistance-associated protein (MRP1) inhibitor described more than a decade ago, is a commercial drug (CAS: 313397-13-6) that has a high price and is six to eight times more potent than known drug transporter inhibitors. However, to date, a complete route for synthesizing pyrazolo[1,5-]pyrimidine-based Reversan is yet to be published. Herein, the silica gel-mediated synthesis of Reversan and a novel family of its structural analogues (amides) the microwave-assisted amidation reaction of 3-carboethoxy-5,7-diphenylpyrazolo[1,5-]pyrimidine (ester) with primary amines is reported.

Photophysical and anion sensing properties of a triphenylamine-dioxaborinine trimeric compound.

Herein, we report the synthesis and photophysical characterization of the novel tris(4-(2,2-difluoro-6-methyl-2-1λ,3,2λ-dioxaborinin-4-yl)phenyl)amine trimeric probe (A2) the reaction between triphenylamine (1), acetic anhydride, and BF·OEt implying the twelve new bond formation in a one-pot manner. This highly fluorescent compound in solution ( up to 0.91 at 572 nm) and solid state ( = 0.

BF-Mediated Acetylation of Pyrazolo[1,5-]pyrimidines and Other π-Excedent (-Hetero)arenes.

An operably simple microwave-assisted BF-mediated acetylation reaction of pyrazolo[1,5-]pyrimidines and a plausible mechanism based on density functional theory (DFT) theoretical calculations for this transformation are reported. Remarkably, and to the best of our knowledge, this is the first example of the direct acetylation for the functional pyrazolo[1,5-]pyrimidine (PP) core. The synthesis of this essential building block is reported in high yields using mild reaction conditions, inexpensive reagents, and even substrates with electron-deficient or highly hindered groups.

Chemosensors based on N-heterocyclic dyes: advances in sensing highly toxic ions such as CN and Hg.

CN and Hg ions are harmful to both the environment and human health, even at trace levels. Thus, alternative methods for their detection and quantification are highly desirable given that the traditional monitoring systems are expensive and require qualified personnel. Optical chemosensors (probes) have revolutionized the sensing of different species due to their high specificity and sensitivity, corresponding with their modular design.

Influence of Steric Effect on the Pseudo-Multicomponent Synthesis of -Aroylmethyl-4-Arylimidazoles.

A pseudo-three-component synthesis of -aroylmethylimidazoles 3 with three new C-N bonds formed regioselectively under microwave conditions was developed. Products were obtained by reacting two equivalents of aroylmethyl bromide (ArCOCHBr, ) with the appropriate amidine salt (RCNH.HX, ) and with KCO as a base in acetonitrile.

Current Advances in Diazoles-based Chemosensors for CN- and FDetection.

Advances in molecular probes have recently intensified because they are valuable tools in studying species of interest for human health, the environment, and industry. Among these species, cyanide (CN-) and fluoride (F-) stand out as hazardous and toxic ions in trace amounts. Thus, there is a significant interest in probes design for their detection with diverse diazoles (pyrazole and imidazole) used for this purpose.

Functional Pyrazolo[1,5-]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold.

Pyrazolo[1,5-]pyrimidine () derivatives are an enormous family of -heterocyclic compounds that possess a high impact in medicinal chemistry and have attracted a great deal of attention in material science recently due to their significant photophysical properties. Consequently, various researchers have developed different synthesis pathways for the preparation and post-functionalization of this functional scaffold. These transformations improve the structural diversity and allow a synergic effect between new synthetic routes and the possible applications of these compounds.

Water-Compatible Synthesis of 1,2,3-Triazoles under Ultrasonic Conditions by a Cu(I) Complex-Mediated Click Reaction.

A new monophosphine Cu(I) complex bearing (pyrazolyl)methane ( ) ( ) was synthesized and used as a catalyst for the three-component click reaction from an alkyl halide, sodium azide, and terminal alkyne to furnish 1,4-disubstituted 1,2,3-triazoles in up to 93% yield. The catalyst is highly stable, compatible with oxygen/water, and works with total efficiency under ultrasonic condition. The structure of the complex was studied and confirmed by X-ray crystallography, finding a riveting relationship with its catalytic activity.

Pyrazolo[1,5-]pyrimidines-based fluorophores: a comprehensive theoretical-experimental study.

Fluorescent molecules are crucial tools for studying the dynamics of intracellular processes, chemosensors, and the progress of organic materials. In this study, a family of pyrazolo[1,5-]pyrimidines (PPs) 4a-g has been identified as strategic compounds for optical applications due to several key characteristics such as their simpler and greener synthetic methodology (RME: 40-53%) as compared to those of BODIPYS (RME: 1.31-17.

Intermolecular interaction energies and molecular conformations in N-substituted 4-aryl-2-methylimidazoles with promising in vitro antifungal activity.

A convenient one-pot synthesis of 4-aryl-2-methyl-N-phenacylimidazoles (4) through a microwave-assisted pseudo-tricomponent reaction of α-bromoacetophenones (1) with acetamidine hydrochloride (2) is reported. Ketones (4) were successfully used as substrates for the preparation of the respective N-(2-hydroxyethyl)imidazoles (5) with yields up to 87%. The synthesized compounds were characterized by NMR and high-resolution mass spectrometry analyses, and several structures were confirmed and studied by single-crystal X-ray diffraction.

Recent progress in chemosensors based on pyrazole derivatives.

Colorimetric and fluorescent probes based on small organic molecules have become important tools in modern biology because they provide dynamic information concerning the localization and quantity of the molecules and ions of interest without the need for genetic engineering of the sample. In the past five years, these probes for ions and molecules have attracted great attention because of their biological, environmental and industrial significance combined with the simplicity and high sensitivity of absorption and fluorescence techniques. Moreover, pyrazole derivatives display a number of remarkable photophysical properties and wide synthetic versatility superior to those of other broadly used scaffolds.

Cyanide chemosensors based on 3-dicyanovinylpyrazolo[1,5-a]pyrimidines: Effects of peripheral 4-anisyl group substitution on the photophysical properties.

Novel dual-mode colorimetric/fluorometric probes based on 3-dicyanovinylpyrazolo[1,5-a]pyrimidines for cyanide (CN) sensing have been developed (DPPa-c). These probes displayed high selectivity and sensitivity toward CN over other interfering anions, with a detection limit (LOD) as low as 610/170 nmol L (absorption/emission) for some of the prepared probes. After a reaction with CN, low-fluorescent DPPa-c showed a significant decrease of the intramolecular charge transfer (ICT) bands at approximately 390 nm (color changes from yellow to colorless) and exhibited up to an 82-fold fluorescence enhancement at approximately 465 nm (strong blue-light emission).

Synthesis of Pyrrolo[2,3-]isoquinolines via the Cycloaddition of Benzyne with Arylideneaminopyrroles: Photophysical and Crystallographic Study.

An efficient and quick access toward a series of ()-2-arylideneaminopyrroles and to their benzyne-promoted aza-Diels-Alder cycloaddition products is provided. These products are three pyrrolo[2,3-]isoquinolines substituted in position 5 with different electron-acceptor (A) or electron-donor (D) aryl groups. Intermediates and products were obtained in good yields (up to 78 and 84%, respectively), and their structures were determined on the basis of NMR measurements and HRMS analysis.

Synthesis, Photophysical Properties, and Metal-Ion Recognition Studies of Fluoroionophores Based on 1-(2-Pyridyl)-4-Styrylpyrazoles.

A convenient access toward novel fluoroionophores based on 1-(2-pyridyl)-4-styrylpyrazoles (PSPs) substituted at position 3 with donor or acceptor aryl groups is reported. The synthesis proceeds in two steps: the first one via Wittig olefination of the appropriate 4-formylpyrazole and then Mizoroki-Heck coupling to yield the desired products in an overall yield of up to 69%. Photophysical properties of products (4-styryl) and their intermediates (4-vinyl) were explored, finding that they have strong blue-light emission with high quantum yields (up to 66%) due to ICT phenomena.

Pyrazolo-fused 4-azafluorenones as key reagents for the synthesis of fluorescent dicyanovinylidene-substituted derivatives.

A green process to access pyrazolo-fused 4-azafluorenones (indeno[1,2-]pyrazolo[4,3-]pyridines, IPP) 4a-x the three-component reaction between indan-1,3-dione (1), benzaldehydes 2 and 5-amino-1-arylpyrazoles 3 is described. These compounds were successfully used as precursors of the novel dicyanovinylidene derivatives 7a-d containing different acceptor (A) or donor (D) aryl groups at position 4 of its fused system. The structures of products obtained (4a-x and 7a-d) were determined based on NMR experiments, HRMS analysis, and X-ray diffraction studies for 7b.

Synthesis of Fluorescent 1,7-Dipyridyl-bis-pyrazolo[3,4-:4',3'-]pyridines: Design of Reversible Chemosensors for Nanomolar Detection of Cu.

An efficient access toward novel tridentate ligands based on 1,7-dipyridinyl-substituted bis-pyrazolo[3,4-:4',3'-]pyridines (BPs) and their usefulness as fluorescent probes for cation detection is reported. The synthesis proceeds by a three-step sequence starting from 2-chloropyridine (), all reactions were performed using microwave radiation under solvent-free conditions, and an overall yield of up to 63% was obtained. Photophysical properties of three representative 1,7-dipyridinyl-BPs (PBPs, -) substituted at position 4 with different donor (D) or acceptor (A) groups were investigated.

Integrated pyrazolo[1,5-a]pyrimidine-hemicyanine system as a colorimetric and fluorometric chemosensor for cyanide recognition in water.

A new probe for cyanide detection based on the integrated pyrazolo[1,5-a]pyrimidine-hemicyanine (PpHe) system was synthesized in an efficient and straightforward manner using microwave-assisted heating. Photophysical studies in a 100% aqueous solution demonstrated high cyanide selectivity and detection limits as low as 600 and 86 nmol L for UV-vis absorption and fluorescence emission, respectively. Both values are well below 1900 nmol L, which is the maximum concentration permitted for drinking water by the World Health Organization (WHO).

Studies via X-ray analysis on intermolecular interactions and energy frameworks based on the effects of substituents of three 4-aryl-2-methyl-1H-imidazoles of different electronic nature and their in vitro antifungal evaluation.

The crystal structures of 2-methyl-4-phenyl-1H-imidazole, CHN, (3a), 4-(4-chlorophenyl)-2-methyl-1H-imidazole hemihydrate, CHClN·0.5HO, (3b), and 4-(4-methoxyphenyl)-2-methyl-1H-imidazole, CHNO, (3c), have been analyzed. It was found that the electron-donating/withdrawing tendency of the substituent groups in the aryl ring influence the acid-base properties of the 2-methylimidazole nucleus, changing the strength of the intermolecular N-H.

3-Formylpyrazolo[1,5- a]pyrimidines as Key Intermediates for the Preparation of Functional Fluorophores.

A one-pot route for the regioselective synthesis of 3-formylpyrazolo[1,5- a]pyrimidines 4a-k in good yields through a microwave-assisted process is provided. The synthesis proceeds via a cyclocondensation reaction between β-enaminones 1 with NH-3-aminopyrazoles 2, followed by formylation with an iminium salt moiety (Vilsmeyer-Haack reagent). These N-heteroaryl aldehydes 4 were successfully used as strategic intermediates for the preparation of novel functional fluorophores with yields up to 98%.

A series of (E)-5-(arylideneamino)-1-tert-butyl-1H-pyrrole-3-carbonitriles and their reduction products to secondary amines: syntheses and X-ray structural studies.

An efficent access to a series of N-(pyrrol-2-yl)amines, namely (E)-1-tert-butyl-5-[(4-chlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, CHClN, (7a), (E)-1-tert-butyl-5-[(2,4-dichlorobenzylidene)amino]-1H-pyrrole-3-carbonitrile, CHClN, (7b), (E)-1-tert-butyl-5-[(pyridin-4-ylmethylene)amino]-1H-pyrrole-3-carbonitrile, CHN, (7c), 1-tert-butyl-5-[(4-chlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, CHClN, (8a), and 1-tert-butyl-5-[(2,4-dichlorobenzyl)amino]-1H-pyrrole-3-carbonitrile, CHClN, (8b), by a two-step synthesis sequence (solvent-free condensation and reduction) starting from 5-amino-1-tert-butyl-1H-pyrrole-3-carbonitrile is described. The syntheses proceed via isolated N-(pyrrol-2-yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz.

Synthesis of Dicyanovinyl-Substituted 1-(2-Pyridyl)pyrazoles: Design of a Fluorescent Chemosensor for Selective Recognition of Cyanide.

A fluorescence "turn-off" probe has been designed and successfully applied to detect cyanide (CN) based on a Michael-type nucleophilic addition reaction and intramolecular charge transfer (ICT) mechanism. For this research, a family of 3-aryl-4-(2,2-dicyanovinyl)-1-(2-pyridinyl)pyrazoles as donor-π-acceptor (D-π-A) systems have been synthesized in 58-66% overall yield, by a three-step synthesis sequence starting from p-substituted acetophenones. The substituted p-methoxyphenyl showed good fluorescence emission and large Stokes shifts in different solvents due to its greater ICT.