Abstract: Throughout history to the present day, infectious diseases have been a persistent global threat, causing significant harm to public health and economic stability. To address these challenges, the development of novel antimicrobial drugs is crucial. Hydrazones have gained significant attention in scientific literature as promising candidates for developing new antimicrobial drugs. Two new hydrazone (H3 and H4) incorporating moieties that are known to enhance the antimicrobial activity were synthesized. Method: The hydrazone derivatives were synthesized through a condensation reaction of substituted acetophenone and nitro phenyl hydrazine. The compounds were characterized by their melting points and spectral analyses, including FT-IR, ¹H NMR, ¹³C NMR, and 2D NMR. Their antibacterial effects on Escherichia coli and Staphylococcus aureus, were assessed in-vitro using the agar diffusion and broth dilution method. Result: In-vitro testing demonstrated good activity against tested organisms, particularly gram-positive bacteria. At a concentration of 50 mg/ml, H3 produces zone of inhibition (19 mm) comparable to the standard ciprofloxacin (20 mm) at 0.05 mg/ml. P5 produces less inhibition in comparison to H3 and H4 producing minimum inhibition (12 mm) at highest concentration of 50 mg/ml. Only H3 was able to kill both Staphylococcus aureus and Escherichia coli at a concentration of 50 mg/ml. In all cases, H3 was found to be the most effective with optimum bactericidal and bacteriostatic activity against staphylococcus aureus and Escherichia coli. Conclusion: All the synthesized compounds were proven to possess a promising antibacterial activity in-vitro against tested organism.

The β-carboline are a group of natural and synthetic indole alkaloids that contain a common tricyclic pyrido[3,4-b]indole ring in their structure. The saturated members are known as tetrahydro-β-carboline (TH-β-Cs) and they are well documented for their biological properties. Natural or synthetic derivatives of TH-β-Cs are privileged molecules because they are present in a wide variety of bioactive compounds and some commercial drugs. On the other hand, 1,5-disubstituted-tetrazoles (1,5-DS-T) are a privileged heterocyclic bioisosteres of the cis-amide bond in peptides by mimicking their structure, polarity, and hydrogen donor/bond sites. The Ugi azide (UA) consists in a four-component condensation of amines, aldehydes, trimethylsilyl azide as hydrazoic acid precursor and isocyanides.

UA is the most efficient methodology for the synthesis of 1,5-DS-T. The combination with post- transformation reactions, for example Pictet Spengler (P-S) allows to increase molecular complexity and diversity of final products. The strategy UA/P-S reaction has been exploited for the construction of complex nitrogen heterocycles , however commonly it involves prolonged reaction times and is carried out at elevated temperatures. Herein we developed the one-pot synthesis of tetrahydro-1H-b-carbolines via the UA)/(P-S) strategy, under mild reaction conditions. The complex product contains two privileged heterocyclic: 1,5-disubstituted-1H-tetrazole and tetrahydro- β-carboline that may find application in medicinal chemistry.

Imidazo[1,2-a]pyridine are nitrogen fused heterocycles which are acknowledged as privileged molecules due their wide range of properties in medicinal chemistry, including anti-diabetic, anti-cancer, anti-viral, anti-ulcer, anti-microbial, anti-IHV, hypnotic, analgesic and antipyretic activities. These scaffolds are also valuable for other fields like bioimaging, probes or chemosensors, due to their optoelectronic properties, which include high quantum yields, large Stokes shifts, and good stability. One-pot processes that include multicomponent reactions are the most efficient, robust, and sustainable synthetic tools for the synthesis of valuable molecules. Among these, isocyanide-based multicomponent reactions stand out as the most versatile and effective tools for the synthesis of heterocyclic molecules directly or via post-transformation. Specifically, the Groebke-Blackburn-Bienaymé (GBB) reaction is the most effective tool for accessing imidazo[1,2-a]pyridine. This reaction involves an aldehyde or ketone, an amidine and an isocyanide, with Lewis or Bronsted acid catalysis. The reactivity of the endocyclic nitrogen in the amidine component allows the intramolecular nitrilium ion trapping, leading to the formation of the heterocyclic scaffold, whereas the acid component is not incorporated in the final products as in classical Ugi reaction. Herein we developed the one-pot synthesis under mild conditions to access functionalized imidazo[1,2-a]pyridine using ammonium chlorine as a catalyst. The resulting GBB products could serve as synthetic platforms for further post-transformations.

In recent decades, hydrazone ligands have been extensively studied due to their versatility in coordination chemistry and because of their important biological properties (anticancer, antifungal, antimicrobial, etc.). These types of ligands are widely used in coordination chemistry, due to the variety of metallo-supramolecular architectures they can form. These include the formation of helicates, mesocates and clusters. Among the most relevant properties of metal complexes derived from hydrazone ligands are their interaction with biomolecules such as DNA, as well as their magnetic or antioxidant properties.

In this work, we present the design and synthesis of the bishydrazone ligand H₃L generated through an iminic condensation reaction between 2-hydroxyisophthalaldehyde and 2-hydroxybenzohydrazide. This synthesis is carried out using acid catalysis and ethanol as solvent. This ligand is bicompartimental, potentially pentadentate [N₂O₃] and trianionic. The presence of a spacer consisting of a phenolic group facilitates the coordination of transition and post-transition metal ions, resulting in a wide variety of metallo-supramolecular structures. Several characterisation techniques in solid state and in solution were used to confirm the formation and purity of the ligand, including elemental analysis, mass spectrometry, infrared spectroscopy and nuclear magnetic resonance. Moreover, it was also possible to analyse the structure of H₃L by X-ray diffraction studies.

The spontaneous association of organic ligands and metal ions has given rise to what is known as Metallosupramolecular Chemistry. This emerging field of chemistry has garnered significant attention due to the various supramolecular structures that can be obtained, which have applications in diverse areas such as materials chemistry, biomedical chemistry, and catalysis, among others. In this context, Schiff Base ligands are among the most used for the synthesis of helicates and mesocates.

In this work, the Schiff Base ligand H₂L was designed, synthesized, and characterized. This ligand is potentially dianionic and tetradentate [N₂O₂], with a long and semiflexible spacer, making it a bicompartmental ligand that promotes the formation of dinuclear helicate compounds. Additionally, the presence of bulky tert-butyl and ethyl groups at specific positions of the skeleton is crucial for enhancing the formation of such structures instead of mesocates. The synthesis was carried out through an imine condensation reaction between two equivalents of 4-(tert-butyl)-2-hydroxybenzaldehyde and one equivalent of 4,4’-methylenebis(2,6-diethylamine) in the presence of p-toluenesulfonic acid monohydrate as a catalyst. The reaction was conducted using absolute ethanol as a solvent, under stirring and reflux for four hours. The ligand was characterized using standard techniques, and suitable crystals were obtained for study by X-ray diffraction.

trans-Substituted porphyrins (ABAB) are commonly synthesized through the reaction of an aldehyde with a dipyrromethane. However, in this acid-catalyzed condensation there is a constant risk of fragmentation followed by recombination. Therefore, this procedure can lead to the rearrangement of meso-substituents, ultimately yielding a mixture of porphyrins.

In this work, different approaches were evaluated to obtain 5,15-bis[4-(N,N-diphenyl)aminophenyl]-10,20-bis(pentafluorophenyl)porphyrin and 5,15-bis[4-(9-carbazolyl)phenyl]-10,20-bis(pentafluorophenyl)porphyrin. In particular, these specific substituent patterns are crucial building blocks in obtaining different materials. First, the reaction of 5-pentafluorophenyldypyrromethane with the corresponding benzaldehyde catalyzed by boron trifluoride diethyl etherate in dichloromethane led to a high level of scrambling that produces a mixture of porphyrins. These products involve ABAB (3%), A₃B (15%) and A₄ (4%) symmetries, where A represents a pentafluorophenyl group. These porphyrins have similar polarities and they are very difficult to separate by column chromatography. Therefore, the reagents were changed to pentafluorobenzaldehyde and dipyrromethane. When 1:1 molar ratio was used, the products were a complex mixture. However, the total yield of porphyrins increased to 20% and 25% with a molar ratio of 0.7:1 and 0.5:1, respectively. Furthermore, in the last case, A₄ porphyrin was not obtained and the main products were ABAB (19%) and A₃B (6%). Therefore, condensation of a dipyrromethane with pentafluorobenzaldehyde provides a general method for the rational synthesis of ABAB-porphyrins in good yield with lower scrambling.

The search for new environmentally friendly synthetic processes that reduce the use and generation of hazardous substances is the main interest of green chemistry. Currently, the main challenges for synthetic chemistry are the design, development, and implementation of more efficient methods. One strategy to achieve this is the use of highly efficient synthesis tools such as Isocyanide-Based Multicomponent Reactions (IMCRs).

IMCRs have recently attracted the interest of various researchers in organic synthesis due to their efficiency in forming several bonds in one reaction step. Reducing the number of steps is crucial for minimizing waste generated during the purification processes of synthesis intermediates, which significantly contributes to the development of environmentally friendly strategies. The synthesis of Imidazo[1,2-α]pyridines (IMPs), via IMCR presents several advantages over multistep and/or conventional syntheses.The Groebke-Blackburn-Bienaymé reaction (GBB) is useful for synthesizing imidazole analogs and is the method of choice for synthesizing IMPs. Multiple properties of IMPs have been reported; however, these reports often describe the synthesis of IMPs using a large number of reagents, high temperatures, long reaction times, and overall low yields. The GBB synthesis of IMPs using cheap and environmentally friendly catalysts, such as ammonium chloride, has been little reported. In the present work, we describe the synthesis of analogues of IMPs functionalizated with the chromone into the imidazole ring, which is widely documented in the design of materials with fluorescent properties.

The design and synthesis of new amino acids a has attracted considerable attention in recent times. Particular attention has been devoted to b-amino acids, on account of the metabolic and conformational stability of b‑peptides. Among them, cyclopentane b-amino acids have become attractive candidates for the stabilization of bioactive peptides, due to the high propensity of their homopolymers to fold in rigid secondary structures in short peptide sequences.

Nitro compounds are very versatile in organic synthesis. In particular, nitroalkenes can act as potent Michael acceptors and, in fact, Michael addition of nucleophiles to nitroolefins is an important tool for the creation of carbon-carbon bonds and heteroatom-carbon bonds. After employing this powerful method for carbon-carbon bond construction, the nitro group can be transformed into a wide variety of functionalities, including amino groups, by reduction.

In connection with our continuing interest in nitro compounds and cycloalkane b-amino acids, we report here the unexplored Michael addition of tris(phenylthio)methane (a synthetic equivalent of the carboxyl group) to a cyclopentane sugar nitroolefin derived from D-glucose ([1R, 2R)-2-(benzyloxy)-4-nitrocyclopent-3-en-1-yl formate], this being the key step in a synthetic sequence that allowed new access to a cyclopentane b-amino acid [methyl (1S,2R,3R,5R)-2-(benzyloxy)-5-((tert-butoxycarbonyl)amino)-3-hydroxycyclopentane-1-carboxylate]. This approach is shorter and more efficient than a previous synthesis of this b-amino acid, also obtained from D-glucose.

Carbohydrates constitute an abundant source of useful scaffolds for the synthesis of highly functionalized carbo- and heterocycles.¹ They provide the stereogenic centers bearing their OH substituents and a proper functionality for the generation of the two C-C or the two C-heteroatom bonds involved in the generation of the carbo- or heterocyclic ring. Two approaches have been developed for these purposes.

Sugar triflates showed to be more suitable for these purposes, due to their easy preparation and their high reactivity, that facilitates the easy and efficient formation of the new ring by intramolecular nucleophilic displacements both prior or after the opening of the sugar ring. The alternative of using sugar dimesylates or sugar ditriflates for the simultaneous formation of the two key bonds leading to the new ring is particularly attractive, but has some limitations. In fact, for the formation of ditriflates from diols, it is necessary the absence of a neighboring hydroxyl group that could lead to intramolecular cyclization, particularly to a five membered ring.

The synthesis of carbocycles and heterocycles from sugar ditriflates is at present practically limited to several synthesis of azetidines. This article reports further chemistry on in this field. It includes new divergent synthesis of iminocyclopentitols anad 3,4-dihydroxyprolines

The arylation of aromatic electrophiles (halogenoaromatics, triflates, diazonium) catalyzed by palladium is known with numerous organometallic aryl nucleophiles of boron (Suzuki-Miyaura), silicon(Hiyama), tin(Stille), zinc (Negishi), mercury (Heck)... which obviously leads to sub -products containing metals. If boron and silicon are only slightly or not toxic, a large majority of metals present a toxicity which can be annoying during the synthesis of molecules for therapeutic purposes. This is particularly the case for tin in the Stille reaction.

We investigated whether it was not possible to use a non-organometallic phenyl anion derived from an elimination reaction as a nucleophilic arylation agent. Tests using a carboxylate or a sulfinate were not successful, on the other hand phenylazocarboxylate led to interesting results. Phenylazacarboxylate was introduced by Nesmeyanov (1948) in the synthesis of arylmercury componds. This compound was not reused, however, and was never tested in catalyzed palladium couplings, unknown at that time. During phenylation, one molecule of nitrogen and one molecule of carbon dioxide are removed.The precursor of phenylazocarboxylate is commercially available 1-phenylsemicarbazide, its oxidation gave of 1-phenyldiazocarboxamide.We obtained potassium phenylazacarboxylate by saponification with potash of 1-phenyldiazocarboxamide under ultrasound irradiation, without heating, in a yield of 81%.

A water-dioxane mixture with a water soluble palladium complexe was used under microwave irradiation with the potassium phenylazocarboxylate. It therefore appears that arylazocarboxylates can be non-organometallic arylnucleophiles in aromatic arylations.