Quite a lot of active pharmaceutical ingredients with various pharmacological effects have been obtained based on pyrimidine hydroxy derivatives. Our attention was drawn to 2-methylpyrimidine-4,6-diol (1). Its 5-formyl derivative has potentially antihypertensive activity with a high probability according to in silico screening data. For the implementation of formylation, the Vilsmeier-Haack method was chosen as the most powerful and effective among the known methods for introducing a formyl group into heterocyclic systems. The aim of the work is to study the Vilsmeier-Haack reaction for substrate 1, to select optimal conditions for obtaining the maximum practical yield with the shortest synthesis time. In the course of the work, the influence of the conditions of the Vilsmeier-Haack reaction for 2-methylpyrimidine-4,6-diol. A comparative analysis of approaches using various solvents (o-xylene,
N,N-dimethylformamide (DMFA), benzene and dichloroethane) as the reaction medium and the optimal one was selected. The amount of Vilsmeier reagent and substrate 1 was strictly equivalent. During the formylation of substrate 1 under the conditions of the Vilsmeier-Haack reaction in the medium of o-xylene, DMFA, benzene and dichloroethane, only 4,6-dihydroxy-2-methylpyrimidine-5-carbaldehyde (2). It should be noted that there was no substitution of hydroxyl groups for chlorine atoms observed in reactions with similar substrates. The synthesis was monitored using the thin-layer chromatography method. The structure of the resulting product 2 was proved using NMR spectroscopy on ¹H and ¹³C nuclei and confirmed by mass spectrometry. Formylation in DMFA medium is characterized by the highest practical yield of product 2, shorter synthesis time, and minimal solvent costs.

Azine compounds has recently gained significant attention due to the interesting properties that they display which could be relevant in fields such as Pharmacology and Material Sciences. These types of ligands recently stand out in Coordination Chemistry because of the facilities that exhibit to easy coordinate to diverse transition and post-transition metal ions. Besides to the azine skeleton (C=N-N=C), the addition of other donor atoms in the brands such as sulphur, oxygen or phosphorus in the ligand increases the coordination possibilities. In this sense, we are interested in azine ligands as precursors of metallosupramolecular architectures which could shown interesting properties.

The research herein reported is focused on the design, synthesis and characterization of a potentially dianionic and tetradentate [P₂O₂] organic phosphino-azine ligand (LP⁸). The addition of the phosphine group to the azine skeleton allows the stabilisation of soft metal ions and the assembly of novel functional structures. The azine ligand LP⁸ has been prepared by an iminic condensation reaction between two equivalents of (diphenylphosphino)benzaldehyde and one equivalent of azine monohydrate. The obtained compound was fully characterized by using several techniques both in solution and in solid state such as elemental analysis, mass spectrometry, infrared spectroscopy, ¹H NMR spectroscopy and X-ray diffraction.

Interactions of nano cobalt chloride in the absence and presence of Schiff base ligands derived from 4,6-diacetyl resorcinol are studied thermodynamically in mixed binary solvent (DMF-H₂O). The organic ligands are nominated as EAH₂DAR and O-PhenH₂DAR. The nano cobalt chloride was characterized by the TEM tool. The calculated parameters depend on the conductivity of solutions measured at different temperatures and concentrations. The study was done at 298.15, 308.15, 318.15, and 328.15 K in various concentrations of a mixed solvent of dimethylformamide and water. The association parameters such as the enthalpies, entropies, free energies of association, degree of association, and association constant were calculated in the absence and presence of Schiff base ligands. The results showed the strong electrolyte behavior of nano cobalt chloride in the absence and presence of organic ligands. The interactions between cobalt species increase after adding Schiff bases ligands where the degree of dissociation decreases in the presence of ligands. Small values of degree of dissociation and s of molar conductance show that the interactions increase in the case of O-PhenH₂DAR than EAH₂DAR ligand. The solution of nano cobalt chloride salt with O-PhenH₂DAR has the highest values of association constants and more negative Gibbs free energies at all temperatures and concentrations used.

This study explores a novel class of chromone-hydrazone derivatives, capitalizing on the chromone scaffold's well-established biological potential and hydrazone moieties' efficient probe for coordination. Through strategic condensation reactions with diverse hydrazine derivatives, we successfully functionalized the chromone core, resulting in a library of structurally varied chromone-hydrazones. Employing ¹H NMR, ¹³C NMR, and FT-IR spectroscopy, the synthesized compounds were meticulously characterized to confirm their structures and elucidate the influence of substituents. This detailed characterization provided insights into the electronic and steric effects imparted by different substituents on the chromone-hydrazone framework.

This work not only enriches the repertoire of chromone-based derivatives but also paves the way for future exploration of their functional applications. The structural diversity of these compounds holds promise for a wide range of applications, reflecting the versatile nature of the chromone scaffold. Notably, the newly synthesized chromone-hydrazones will be evaluated for their potential as chemosensors for metal ions, anions, and small pollutant/critical molecules. These investigations are expected to open exciting avenues for biological, environmental, and analytical applications, showcasing the practical utility of these derivatives in real-world scenarios. By expanding the understanding and application of chromone-hydrazone derivatives, this study sets the stage for innovative advancements in chemosensing technologies and beyond.

In this paper, a novel, cost-effective, and green methodology has been investigated for preparation of cobalt (II) nanoparticles supported on the nanodiamond carbon structure-grafted-polyethyleneimine@folic acid (ND-g-PEI@FA@Co(II)) nanocomposite. Some of the physicochemical characteristics of the synthesized efficient heterogeneous nanocatalyst, including bond formation and functional groups, percentage of elements, crystalline phase, and surface morphology were studied using techniques such as Fourier Transform Infrared Spectroscopy (FT-IR), Energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Field emission scanning electron microscopy (FE-SEM). Following the principles of green chemistry, this nanocatalyst has been used in the production of 5-substituted 1H-tetrazole derivatives using different benzaldehyde derivatives, sodium azide and malononitrile agents in ethanol eco-friendly solvent with high efficiency. The mechanism of tetrazole synthesis is carried out through cascade condensations, such as knoevenagel condensation, 1,3-dipolar cycloaddition, and tautomerization reactions. The main advantages of ND-g-PEI@FA@Co(II) nanocatalyst include facil preparation, easy separation, low consumption of catalyst for this multi-component reaction (MCR), use of cheap and recyclable materials, excellent product yield, and reusability up to 4 times with good efficiency. The substrate used in this heterogeneous catalyst (ND) with appropriate thermal stability, abundant availability in large quantities, non-toxicity are prominent features of the synthesized nanocomposite.

Studies show that compounds such as 1,3-oxazine-6-ones are promising starting reagents that allow to obtain various acyclic and heteroaromatic systems. These substances demonstrate a wide range of biological activity. Meanwhile, it is known that depending on 1,3-oxazine cycles number in molecule, pharmacological activity may vary. Therefore, purpose of our work was to study reaction of benzene-1,4-dicarboxamide with methylmalonyl dichloride as the most rational way to obtain new compounds of given structure. This interaction can potentially lead to both mono- and bis(1,3-oxazine-6-one) derivatives. Reaction between terephthalamide and methylmalonyl dichloride was conducted at their equimolar ratio and with twofold excess of the latter. Syntheses were carried out in two media: absolute benzene and 1,2-dichloroethane. Reaction of equimolar amounts of reagents resulted in obtaining the only product 4-(4-hydroxy-5-methyl-6-oxo-6H-1,3-oxazine-2-yl)benzamide (1). In twofold excess of methylmalonyl dichloride, just product 1 was obtained after 24 hours of refluxing and after 58 hours only 2,2'-(benzene-1,4-diyl)bis(4-hydroxy-5-methyl-6H-1,3-oxazine-6-one) (2) formed. Determination of partial negative charge on nitrogen atoms of amido groups of terephthalamide and compound 1 allowed us to confirm sequential formation firstly of mono- (1) and then bis(1,3-oxazine-6-one) derivative (2) in reaction mass. Structure of obtained compounds was proved by NMR spectroscopy on ¹H and ¹³C nuclei. When studying solvent influence on synthesis rate, no significant differences were noted between benzene and 1,2-dichloroethane. However, the yield of 2,2'-(benzene-1,4-diyl)bis(4-hydroxy-5-methyl-6H-1,3-oxazine-6-one) during synthesis in 1,2-dichloroethane was lower – 77% compared with 85% in benzene.

The 2-pyridones have at least three active sites based on the presence of the non-substituted "NH ", "C=O", and "CN" groups. The regioselectivity of N- versus O-alkylation depends on various factors, including the nature of metals, the structure of alkyl halides, the substituents on the 2-pyridone ring, solvents, and temperature. Due to the ambiditious nucleophilic characters of 2-pyridones, we have paid considerable attention to these fragments synthesis which can be versatile reagents for accessing bioactive compounds.
In this work, we present new methods of synthesis of different molecules including a 2-pyridone nucleus under ecological conditions, including effective multi-component syntheses, solvent-free, and under microwave irradiation. The products were successfully obtained in a very short reaction time. First, we prepared a series of 1H-free 2-pyridones and N-alkyl 2-pyridones from ethyl cyanoacetate, aromatic aldehydes, various acetophenone derivatives and ammonium acetate or diamino-alkane. These molecules have served as building blocks that, in conjunction with acyl chloride derivatives, glycoside derivatives, etc. have resulted in various heterocyclic hybrid structures carrying a 2-pyridone ring. Moreover, based on the cyano group reactivity of the 2-pyridone ring, we synthesized 5-pyridone 1H-tetrazole in a single step by a cycloaddition reaction [3+2] between 3-cyano-2-pyridone nitriles and sodium azide in the presence of metal-free L-proline.

Within the area of study of neurodegenerative diseases, particularly Alzheimer's disease (AD), this research focused on the synthesis and evaluation of novel tetrahydroquinoline (THQ) derivatives with potential antioxidant activity. The toluidine N-propargylation synthesis protocol was optimized, achieving a significant increase in yield by using sodium carbonate and reaction temperature variation. Subsequently, four THQs compounds with alkene variation were successfully synthesized, including some not previously reported in the literature. The synthesized compounds were characterized by nuclear magnetic resonance (NMR), mass spectrometry, and infrared spectroscopy (IR), which confirmed their structures and purity. In silico analyses performed with SwissADME and OSIRIS Property Explorer indicated that most of the compounds exhibited excellent drug-like characteristics and favorable pharmacokinetic profiles. Antioxidant evaluation was performed using DPPH and ABTS assays where vinyl-formamide THQ and indene THQ demonstrated excellent antioxidant capacity, with EC50 values below 2 μg/mL in the ABTS assay, significantly outperforming the ascorbic acid control (EC50 = 35 μg/mL). The results suggest that the predominant radical scavenging mechanism is single electron transfer (SET). This study provides a solid foundation for further investigations into the potential of THQs derivatives as antioxidants and potential cholinesterase inhibitors in the context of neurodegenerative diseases such as Alzheimer's. As a future projection, an enzymatic evaluation, including mechanism of action and the exploration of a hybrid synthesis of THQ/triazole is proposed based on these promising results.

Diversity Oriented Synthesis and asymmetric aminocatalysis constitute two important tools to access new compounds of interest. The extraordinary development of these two areas has allowed chemists to populate new regions of chemical space. Therefore, new libraries of complex and diverse structures are available for the development of new drugs. In recent years, the term Aminocatalytic privileged-structure Diversity Oriented Synthesis (ApDOS) has been conceptualized, highlighting its potential towards the asymmetric synthesis and diversification of privileged structures, small base molecules of complex natural architectures that usually present important biological activities.

Herein, we present the development of new organocatalytic cascade reactions for the synthesis and diversification of privileged structures, using trienamine activation as a key step. An important feature of this process is that once it has been completed, it is possible to generate new reactive species within the same molecule. In this sense, a series of consecutive reactions can be carried out incorporating dienophiles with an addition-nucleophilic functionality. As a result, complex and diverse compounds can be accessed through simple starting materials. It should be noted that, under this methodology, it will be possible to obtain polycyclic structures with up to four stereogenic centers. The choice of catalyst will be of great importance to enable processes with a high degree of stereoselectivity

1. Pawar, T. J., Jiang, H., Vázquez-Guevara, M. A., Villegas-Gómez, C., Cruz-Cruz, D. Eur. J. Org. Chem. 2018, 16, 1835.

2. Gómez, C. V., Cruz, D. C., Mose, R., Jørgensen, K. A. Chem. Commun., 2014, 50, 6035.

1,5-disubstituted tetrazoles are bioisosteres of cis-amide bond in peptides by adopt their steric conformation, which have contributed to decrease toxicity, increase potency, improve stability, selectivity, and pharmacokinetic properties in peptidomimetics. Additionally, they have been used as bidentate ligands, chelating agents, metal-organic framework precursors, bioimaging agents, energetic materials such as explosives, propellants and pyrotechnics. Isocyanide based multicomponent reactions have proven to be versatile synthetic tools for the synthesis of heterocycles, specifically the Ugi-azide reaction is the best tool to access 1,5-disustituted tetrazoles under mild conditions, in which orthogonal reagents can be included into components to increase its synthetic potential. The Ugi-azide reaction involve an aldehyde or ketone, an amine, an isocyanide and replaced the carboxylic acid used in the classical Ugi reaction by hydrazoic acid. In that the imine is protonated by hydrazoic acid and the remaining azide anion captures the intermediate nitrilium ion, leading to the formation of the final 1,5-disubstituted tetrazole. In the past, Ugi was using isolated hydrazoic acid in a benzene stock solution. Nowadays, trimethylsilyl azide is often used as a safer alternative to azide source, generating hydrazoic acid in situ in protic solvents. Herein we developed a one-pot synthesis under mild conditions to access functionalized 1,5-disubstituted tetrazoles which could be synthetic platforms for further post-transformations.