Heteroaromatic Aldehydes Research Articles

One-pot synthesis of new benzo[4,5]imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a] pyrimidines as an eco-friendly and effective method catalyzed by acetic acid with prospective antimicrobial agents

A novel set chalcones 3a-d was efficiently synthesized in elevated produces across the condensing process of Claisen-Schmidt. An eco-friendly and efficient process was designed for creating a novel desired products 5a-f and 7a-f, respectively with excellent yields. This synthesis was accomplished by reacting acetophenone derivatives 1a-d, heteroaromatic aldehydes 2a,b and aminobenzoimidazole 4 or 3-aminopyrazole 6a,b, using acetic acid as both the catalyst and solvent. Solvent optimization was performed during the synthesis of the desired compounds 5a or 7a, highlighting the benefits of using acetic acid that is harmless for the environment, which offers easy procedure, rapid reaction, elevated efficiency and broad tolerance of starting materials. The preferred products were verified through compatible spectroscopic data. The antimicrobial efficacious for all compounds was successfully evaluated against various microorganisms, revealing that 3b exhibited significant antimicrobial activity across all tested microbes, with measurements of the minimum inhibitory concentrations being between 4.80 to 63.8 μM.

Visible Light-Mediated Co(II) Catalyzed Synthesis of α,β-Epoxy Ketones by Oxidative Coupling of Alkenes and Aldehydes in Water.

A one-step, two-component visible light-mediated CoCl2·6H2O-catalyzed oxidative acylation of alkenes by aldehydes to synthesize α,β-epoxy ketone has been achieved in water at room temperature. The photocatalytic activity of Co(II) presented a remarkable achievement for synthesis of α,β-epoxy ketones from aldehydes and olefins, with a wide substrate compatibility including aromatic, heteroaromatic and aliphatic aldehydes, styrenes with both electron-donating and withdrawing groups, α-substituted styrenes, stilbene, acrylates, and even the challenging unactivated aliphatic alkenes. Mechanistic studies including radical trapping experiments, intermediate detection by GCMS, Hammett analysis, and DFT studies unveil the nature of the photocatalytic pathway.

Photo-Activated Carbon Dots as Catalysts in Knoevenagel Condensation: An Advance in the Synthetic Field

Photoinduced chemical reactions and the development of new materials represent a current and significant topic. We present a sustainable and eco-friendly approach to the Knoevenagel condensation reaction involving carbonyl and active methylene compounds. Our method utilizes photo-activated carbon dots (CDs) derived from 5-hydroxymethylfurfural (5HMF) within an aqueous medium and does not require acidic, basic, or thermal conditions. This protocol operates effectively with aromatic, aliphatic, and heteroaromatic aldehydes and ketones. The 5HMF-derived-CDs can be reused four times without significant loss of activity. Moreover, this methodology is suitable for scaling up reactions, thereby highlighting its potential for industrial applications.

Tetrabutylammonium hydroxide (TBAH) ionic liquid for the sustainable and efficient production of α-hydroxyphosphonates

Ionic liquids were known as eco-solvents/catalysts, encourages the clean hydrophosphonylation of aldehydes to produce structurally various α-hydroxyphosphonates in a well-organized and ecologically friendly manner. This study used tetrabutylammonium hydroxide (TBAH) used to addition phosphite nucleophiles to aldehydes under neat condition, resulting in different α-hydroxyphosphonates that are essential components of the modern chemical industry. The current method produces targeted compounds from a wide range of aromatic, and heteroaromatic aldehydes with various substitution. The current protocol has high impact because it allows for the formation of desired products in good yields. This catalyst is applicable for gram scale synthesis of the targeted product and without any additional energy (Microwave, ultrasonication, ball milling and thermal heating). Some reported methods used various external sources (mechano-chemical) for the synthesis of α-hydroxyphosphonates.

Microwave Assisted Benzoin Condensation using N,N-Dimethylbenzimidazolium Iodide as an Efficient Greener Catalyst in Neutral Ionic Liquid [Bmim]BF4

The utilization of N,N-dimethylbenzimidazolium iodide as a catalyst in [Bmim]BF4 for benzoin condensation under microwave irradiation demonstrates its efficiency and eco-friendliness. This method enables the synthesis of α-hydroxy carbonyl compounds from various aromatic and heteroaromatic aldehydes with significant yields, ranging from good to high (89-96%). The reactions proceed swiftly, yielding no detectable byproducts. Moreover, the recycled reaction media, comprising benzimidazolium salt and NaOH after extraction, can be reused multiple times without a significant loss of efficiency.

Nucleic Acid-Templated Synthesis of Cationic Styryl Dyes in Vitro and in Living Cells.

A novel method for synthesizing cationic styryl dyes through a nucleic acid-templated reaction has been developed. This approach overcomes issues associated with traditional synthesis methods, such as harsh conditions, low throughput, and wasteful chemicals. The presence of a nucleic acid template accelerated the styryl dye formation from quaternized heteroaromatic and cationic aldehyde substrates. These styryl dyes show remarkable optical properties change when bound to nucleic acids, hence the success of the synthesis could be readily monitored in situ by UV-Vis and fluorescence spectroscopy and the optical properties data were also observable at the same time. This method provides the desired products from a broad range of coupling partners. By employing different substrates and templates, it is possible to identify new dyes that can bind to a specific type of nucleic acid such as a G-quadruplex. The templated dye synthesis is also successfully demonstrated in live HeLa cells. This approach is a powerful tool for the rapid synthesis and screening of dyes specific for diverse types of nucleic acids or cellular organelles, facilitating new biological discoveries.

Effective and Scalable General Method for the Preparation of Enantiomeric (α‐Aminoalkyl)dimethylphosphine Oxides

AbstractThe Ti(OPr‐i)4‐mediated three–component condensation of enantiomeric Ellman's amides, dimethylphosphine oxide, and aliphatic, aromatic or heteroaromatic aldehydes proceeds in high yields and diastereoselectivities enabling the rapid, scalable and general asymmetric synthesis of (α‐amino)dimethylphosphine oxide derived compounds bearing alkyl, cycloalkyl or hetaryl group at the chiral carbon atom. Asymmetric synthesis of α‐amino‐α‐polyfluoroalkyl dimethylphosphine oxides was accomplished through diastereoselective addition of dimethylphosphine oxide to enantiomeric Ellman's aldimines, RFCH=NS(O)tert‐Bu (RF=CF3, CHF2, PhCF2).

Design, Synthesis, and In Vivo Evaluation of a New Series of Indole-Chalcone Hybrids as Analgesic and Anti-Inflammatory Agents.

Indole-chalcone hybrids have burst into prominence as potent weapons in the battle against pain and inflammation due to their unique features, allowing these ligands to form pivotal interactions with biological targets. In this context, the base-catalyzed Claisen-Schmidt condensation of 3',4'-(methylenedioxy)acetophenone with heteroaromatic aldehydes carrying an indole scaffold yielded new chalcones (1-7). The central and peripheral antinociceptive activities of all chalcones (compounds 1-7) at the dose of 10 mg/kg (i.p.) were evaluated by hot plate (supraspinal response), tail immersion (spinal response), and acetic acid-induced writhing tests in mice. The anti-inflammatory activities of compounds 1-7 were also investigated by means of a carrageenan-induced mouse paw edema model. The results revealed that compounds 1-7 extended the latency of response to thermal stimulus significantly in a hot-plate test similar to dipyrone (300 mg/kg; i.p.), the positive control drug. However, only compounds 2-7 were found to be significantly effective in the tail-immersion test. Compounds 1-7 also significantly showed analgesic effect by reducing the number of writhes and anti-inflammatory activity by inhibiting edema formation at different time intervals and levels. 1-(1,3-Benzodioxol-5-yl)-3-(1-methyl-1H-indol-2-yl)prop-2-en-1-one (4) drew attention by providing the highest efficacy results in both acute analgesia and inflammation models. Based on the in silico data acquired from the QikProp module, compound 4 was predicted to possess favorable oral bioavailability and drug-like properties. Taken together, it can be concluded that chalcones (1-7), especially compound 4, are outstanding candidates for further research to investigate their potential use in the management of pain and inflammation.

Green chemistry approach to the synthesis of 2-aryl/heteroaryl substituted 2,3-dihydroquinazolin-4(1H)-ones using lemon juice under concentrated solar radiations as a renewable source.

This study explores a novel and eco-friendly synthesis of 22 derivatives of 2-aryl/heteroaryl substituted 2,3-dihydroquinazolin-4(1H)-ones, compounds with significant medicinal potential, using concentrated solar radiation (CSR) and lemon juice as a natural catalyst. Traditional methods for synthesizing these compounds often involve complex, energy-intensive processes and toxic reagents. In contrast, the method presented here utilizes solar energy and a biodegradable, non-toxic catalyst, aligning with the principles of green chemistry. The reaction, involving 2-aminobenzamide and various aromatic and heteroaromatic aldehydes, was optimized by varying temperature, catalyst concentration, and solvent. Through optimization, a combination of 0.3 mL of lemon juice and CSR achieved a 97% product yield in 10 minutes. A wide range of aromatic and heteroaromatic aldehydes were tested, all of which produced excellent yields, confirming the method's broad applicability. The substrate scope was explored with different aldehydes, containing groups/structures like chloro, bromo, nitro, methyl, methoxy, fluoro, hydroxy, imidazole, thiazole, chromone, pyrrole, and 1,4-dioxane, yielding up to 97%. Comparative studies with other catalysts and solvents confirmed the superior efficiency of lemon juice. This study not only demonstrates a sustainable approach to synthesizing 2,3-dihydroquinazolin-4(1H)-ones but also highlights the potential of solar energy in organic synthesis, offering a viable alternative to conventional methods. This environmentally benign method offers an efficient and sustainable route for synthesizing 2,3-dihydroquinazolin-4(1H)-one derivatives.

Chemoselective oxidation of aromatic aldehydes to carboxylic acids: potassium tert-butoxide as an anomalous source of oxygen.

Chemoselective oxidation of aromatic and heteroaromatic aldehydes (>45 examples) to their corresponding carboxylic acids has been developed. Potassium tert-butoxide acts as an oxygen source during this transformation that delivers the corresponding acids without chromatographic purifications. The use of bench-top reagents, operational simplicity, and high level of chemo-selectivity with respect to oxidation of the least preferred aldehyde functionality, in the presence of more susceptible functional groups, are some of the highlights of this strategy.

Comparison of simultaneous saccharification and fermentation with LPMO-supported hybrid hydrolysis and fermentation.

Enzymatic saccharification is used to convert polysaccharides in lignocellulosic biomass to sugars which are then converted to ethanol or other bio-based fermentation products. The efficacy of commercial cellulase preparations can potentially increase if lytic polysaccharide monooxygenase (LPMO) is included. However, as LPMO requires both a reductant and an oxidant, such as molecular oxygen, a reevaluation of process configurations and conditions is warranted. Saccharification and fermentation of pretreated softwood was investigated in demonstration-scale experiments with 10m3 bioreactors using an LPMO-containing cellulase preparation, a xylose-utilizing yeast, and either simultaneous saccharification and fermentation (SSF) or hybrid hydrolysis and fermentation (HHF) with a 24-hour or 48-hour initial phase and with 0.15 vvm aeration before addition of the yeast. The conditions used for HHF, especially with 48h initial phase, resulted in better glucan conversion, but in poorer ethanol productivity and in poorer initial ethanol yield on consumed sugars than the SSF. In the SSF, hexose sugars such as glucose and mannose were consumed faster than xylose, but, in the end of the fermentation >90% of the xylose had been consumed. Chemical analysis of inhibitory pretreatment by-products indicated that the concentrations of heteroaromatic aldehydes (such as furfural), aromatic aldehydes, and an aromatic ketone decreased as a consequence of the aeration. This was attributed mainly to evaporation caused by the gas flow. The results indicate that further research is needed to fully exploit the advantages of LPMO without compromising fermentation conditions.

Efficient synthesis, crystal structure, Hirshfeld surface analysis, biological evaluation, DFT calculations and Docking study of pyrano[4,3-b]pyran derivatives

In this work we describe a simple and rapid method for the synthesis of a series of pyrano[4,3-b]pyran derivatives by a three-component reaction between 4‑hydroxy-6-methylpyran-2-one, malononitrile and a variety of aromatic and heteroaromatic aldehydes. The reactions are carried out at reflux of a water/ethanol mixture in the presence of 10 mol% of pyridinium p-toluenesulfonate as catalyst with excellent yields of expected products. The antimicrobial and anti-Alzheimer's activities of the prepared products were evaluated and some molecules gave interesting results. In addition, theoretical studies such as Density Functional Theory (DFT), IR and UV–visible spectra and molecular docking have also been carried out. Moreover, the molecular structure of one compound was confirmed by X-ray diffraction analysis with its Hirshfeld surface analysis.

Facile Synthesis of Substituted 2-Styrylnaphthyridine and its Derivatives via sp3 C-H Functionalization under Mild Conditions and their Antimicrobial Activity

A simple, metal free strategy is described for the synthesis of substituted 2-styryl-1,8-naphthyridines and pyrazole, imidazopyridine based styryl conjugates under basic mild conditions (piperidine in ethanol) at 70 ºC. The reaction progressed via sp3 C-H functionalization of substituted methyl-1,8-naphthyridines with various aromatic, heteroaromatic aldehyde substrates by Knoevenagel condensation to provides functionalized pyrazole, imidazopyridine based styryl-1,8-naphthyridines in good to excellent yields (85-95%) at impressive reaction time. This approach involves a common organocatalyst, cheap starting materials and shorter reaction times. An extensive variability of substrates was tolerated well to afford the desired products. Furtherly, all the synthesized derivatives were tested for their biological activity, i.e., antibacterial and antifungal. In tested series, compounds 3c, 3d, 3e, 3i, 3k, 3l, 4c, 4d and 4f established excellent inhibition zone of activity against standard drugs.

Incorporation of gem-Difluorocycloalkyl Substituents into Heterocycles via the Levin’s “Nitrogen Deletion” Strategy

A series of compounds containing heterocyclic cores and gem-difluorocycloalkyl substituents was obtained under conditions of the parallel synthesis (i.e., simultaneous performance of reaction procedures, treatment of the reaction mixture, and product isolation for a number of similar transformations) using the reductive amination – the “Nitrogen deletion” reaction sequence. The synthesis of the target compounds commenced from heteroaromatic aldehydes and the corresponding gem-difluorocycloalkyl or (gem-difluorocycloalkyl)methyl amines and included the NaBH3CN-mediated reductive amination and “Nitrogen deletion” upon the action of Levin’s anomeric amide. It has been shown that the method can be used to obtain compounds with the aforementioned structural fragments separated by one or two methylene units. The developed protocol allowed for the preparation of a 12-member compound library (67 % synthetic efficiency). Therefore, this novel synthetic methodology is suitable for decorating heterocyclic cores with sp3-enriched substituents that are attractive for medicinal chemistry.

K2CO3-nanoparticles catalyzed the synthesis of 3-arylidine imidazo[1,2-c]pyrimidine candidates: Cytotoxic activity and docking study

The present work describes an green and eco-friendly synthetic protocol, and vitro anti-proliferative activity of a new series of 3-arylidine imidazo[1,2-c]pyrimidines. The target molecules 4a–p were synthesized via one-pot cyclization of 6-amino-4-(4-chlorophenyl)-2-thioxo-1,2-dihydropyrimidine-5-carbonitrile(1) with chloroacetyl chloride followed by condensation with a series of aromatic and heteroaromatic aldehydes in the presence of K2CO3-NPs at room temperature. The high yield (80–96%), mild reaction conditions (short reaction time and no heat needed), simple purification, and soft, cheap, high efficiency readily available and stability of K2CO3-NPs are evident features of the present approach. Pyrimidines 4c, 4 g and 4i demonstrated significant anti-proliferative activity against MCF-7 especially compound 4i was found to be the most effective among the tested compounds with IC50 values 3.83 µg/ml in MCF-7 cell line compared to the standard drug doxorubicin. In addition, compounds 4b, 4c, 4d, 4i, and 4n demonstrated high cytotoxic activity against HCT116, particularly compound (4b) was the most potent among the tested compounds with IC50 values 9.3 µg/ml in HCT116 cell line compared to doxorubicin.

Synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives as potential inhibitors of TNF-α

'The anti-inflammatory activities of the 2,3-dihydroquinazolin-4(1H)-one derivatives along with results from our in silico predictions (this study) encouraged us to explore this class of compounds as potential inhibitors of TNF-α. Among all the molecules assessed in silico the best ranked molecules were identified with the order as 3h > 3p > 3l based on the estimated total energy. The compound 3h participated in a H-bond interaction through its C = O group of the quinazoline-4(1H)-one ring with TYR151 of chain A in addition to the interactions with all the critical TYR residues via its chloro group. The interesting docking results were also obtained for compound 3l and 3p. For the access of this class of fused N-heteroarenes we adopted the β-cyclodextrin (β-CD) catalyzed approach involving the cyclocondensation of 2-aminobenzamide with aldehydes / ketones in pure water. Various aromatic, aliphatic and heteroaromatic aldehydes (including the cinnamaldehyde) along with ketones were employed for this purpose to afford the corresponding product in good to excellent yield. The recovery and recycling of the catalyst β-CD was successful. The inexpensive and eco-friendly nature along with the simple product purification as well as good product yield are the key advantages of this approach. When examined in vitro the compound 3h, 3l and 3p with the inhibition > 70% emerged as the most active compounds in this series as predicted by in silico studies. According to the SAR (Structure Activity Relationship) the effectiveness of the C-2 aryl group was found to be in the order Ar = C6H4Cl-p > 4-pyridyl > C6H4OMe-p > C6H2(OMe)3-m,p > C6H4OH-p etc. whereas an heteroaryl or alkyl group at this position was found to be less effective or ineffective. In terms of IC50 values the compound 3h, 3l and 3p appeared as superior than the known inhibitor thalidomide though they were not better than rolipram. Being identified as preliminary hits these compounds are of further pharmacological interest.

One-pot synthesis of 2,6-diaryl-4,5-dihydropyridazin-3(2H)-ones: Copper catalyzed annulation of aldehydes, arylhydrazines and 3-acryloyloxazolidin-2-one

The three-component synthesis of pyridazinones from aldehydes, arylhydrazines and 3-acryloyloxazolidin-2-one catalyzed by Cu(OTf)2 has been developed. This strategy exhibits high tolerance towards many functional groups including various aliphatic, aromatic and hetero-aromatic aldehydes to give 2,6-diaryl-4,5-dihydropyridazin-3(2H)-one products in moderate to high yields.

Facile chemoselective dithioacetalization of carbonyl compounds promoted by Fe3O4@MCM-41-GPTMS-Gu-CuIINPs as an efficient magnetic nanostructured catalyst

Dithioacetalization, as a well-known class of organic transformation, was carried out for protection of a wide variety of aromatic (with electron releasing and electron withdrawing substituents), heteroaromatic and aliphatic aldehydes as well as ketones by 1,2-ethanedithiol/or 1,3-propanedithiol in the presence of Fe3O4@MCM-41-GPTMS-Gu-CuIINPs. The corresponding 1,3-dithiolanes and 1,3-dithianes were obtained chemoselectively in the presence of Fe3O4@MCM-41-GPTMS-Gu-CuIINPs with hexagonal core-shell structure, superparamagnetic behavior, and average particle size of 8–25 nm under mild reaction conditions. The nanostructured catalyst could be separated easily from the reaction mixture using a magnetic bar and reused in several reaction runs without any remarkable reduction in its catalytic activity. Nearly neutral conditions, good to high yields of the products, operational simplicity, easy work-up procedure, compatibility with various functional groups make the present method valuable in addition to the known methodologies.

Potent heteroaromatic hydrazone based 1,2,4-triazine motifs: synthesis, anti-oxidant activity, cholinesterase inhibition, quantum chemical and molecular docking studies

1,2,4-Triazine based hydrazone scaffolds possessing impressive biological activities are synthesized using heteroaromatic aldehydes. The target molecules were characterized by detailed spectroscopic techniques. Anti-oxidant capacities of target compounds were determined using DPPH free radical scavenging activity, ABTS method and superoxide anion scavenging assay by means of NBT. Compound 4a displayed potent anti-oxidant potential against ABTS having IC50 28.09 ± 0.15 µM comparative to the standard Trolox (26.01 ± 0.02 µM). Cholinesterase inhibitory potentials of the synthesized compounds were also evaluated, where compound 4b intensely inhibited against AChE and BChE in dose dependent method compared to standard drugs, allanzanthane and galantamine. The IC50 value of compound 4b for AChE was 15.24 ± 0.03 µM vs 10.13 ± 0.01 for allanzanthane and 13.01 ± 0.02 for galantamine, whereas, IC50 value of 4b for BChE was 17.01 ± 0.6 µM vs 22.00 ± 0.01 for allanzanthane and 26.02 ± 0.09 for galantamine. Density functional theory (DFT) simulations of synthesized compounds (4a-c) complement the experimental spectroscopic data (FTIR, 1H & 13C NMR & UV–Visible). The HOMO-LUMO energy gaps of 3.58 eV to 3.80 eV reflect the kinetic stability of the compounds (4a-c). Moreover, the MEP analysis confirmed the chemical reactivities of these compounds and more nucleophilic sites were identified at the heteroatoms of heterocyclic moiety and triazine moiety. In silico molecular docking study revealed that our active targeted compounds have minimum binding energy and good affinity toward the active pocket of target protein. These results showed that our synthesized compounds are excellent inhibitors of AChE & BChE enzymes, and therefore, can be subjected to further studies in order to accomplish potent drug responsible for the treatment of Alzheimer's disease.

α,β-Unsaturated CF3-ketones via secondary amine salts-catalyzed aldol condensation of 1,1,1-trufluoroacetone with aromatic and heteroaromatic aldehydes

A facile and efficient approach to the synthesis of α,β-unsaturated CF3-ketones in moderate to excellent yields via the amine salt-catalyzed aldol condensation of aromatic and heteroaromatic aldehydes with trifluoroacetone has been developed.