Work-up Procedure Research Articles

Efficient Formylation of Alcohols Using a Core-Shell Magnetic Nanocomposite via Vilsmeier-Haack Complex Formation

Introduction: The protection of the hydroxyl group as formamides is a crucial initial step in pharmaceutical synthesis. Methods: In this study, we investigated the O-formylation of alcohols using dimethylfor-mamide (DMF) in a mixture with a new magnetic nanocomposite Fe3O4@Chitosan/POCl2-x. Results: The results demonstrate that this core-shell heterogeneous nanocomposite facili-tates the formation of alkylformate, yielding products with high efficiency ranging from 79% to 96% within a remarkably short reaction time of 1 to 12 hours at room temperature, depending on the substrate structure. Significantly, the presence of this nanocomposite ex-hibits remarkable selectivity, favoring the formylation of less hindered benzylic and ali-phatic primary alcohols. However, bulkier alcohols and phenols exhibit lower reactivity under these conditions and thiols do not react. The simplicity of the work-up procedure, combined with the magnetic recyclability, makes it reusable and environmentally friendly. Conclusion: This study highlights the efficacy of this novel magnetic nanocomposite in facilitating formylation reactions, emphasizing its potential for application in pharmaceu-tical synthesis and bio compounds. This is due to its attributes of non-toxic nature, stabil-ity, and significant advantages over conventional methodologies.

Safety and Feasibility of Interventional Hybrid Fluoroscopy and Nuclear Imaging in the Work-up Procedure of Hepatic Radioembolization.

Purpose To evaluate the safety and feasibility of a novel hybrid nuclear and fluoroscopy C-arm scanner to be used during the work-up procedure of hepatic radioembolization. Materials and Methods In this prospective first-in-human clinical study, 12 participants (median age, 67 years [range: 37-78 years]; nine [75%] male, three [25%] female) with liver tumors undergoing work-up for yttrium 90 radioembolization were included (ClinicalTrials.gov NCT06013774). Work-up angiography and technetium 99m-macroaggregated albumin injection were performed in an angiography suite equipped with a hybrid C-arm that could simultaneously perform fluoroscopy and planar nuclear imaging. Technetium 99m-macroaggregated albumin was injected under real-time hybrid imaging, followed by in-room SPECT imaging. Safety and feasibility were studied by assessing adverse events, technical performance, additional x-ray radiation dose, and questionnaires completed by radiologists and technologists. Results No adverse events were attributed to the hybrid C-arm scanner. The additional x-ray radiation dose was low (median, 19 Gy · cm2; minimum: 12 Gy · cm2; maximum: 21 Gy · cm2 for participants who completed all imaging steps). The interventional personnel considered use of the hybrid C-arm scanner safe and feasible, although the additional time spent in the intervention room was considered long (median, 64 minutes; minimum: 55 minutes; maximum: 77 minutes for participants who completed all imaging steps). Conclusion Use of the hybrid C-arm scanner during the work-up procedure of hepatic radioembolization was found to be safe and feasible in this first-in-human clinical study. Keywords: Angiography, Fluoroscopy, Interventional-Vascular, Radionuclide Studies, Radiosurgery, Gamma Knife, Cyberknife, SPECT, Instrumentation, Physics, Technical Aspects, Technology Assessment Supplemental material is available for this article. Published under a CC BY 4.0 license. Clinical trial registration no. NCT06013774.

Mild acidic charcoal: adsorption, analysis, and application.

The adsorption of glacial acetic acid over a charcoal support was investigated. The amount of adsorption was analyzed using a traditional titration method and the prepared adsorbed system was employed as a heterogeneous catalyst for organic reactions as a viable application. Different 14-aryl-14H-dibenzo[a,j]xanthenes were synthesized using mild acidic charcoal as a catalyst and yields of 88%-94% were obtained. The advantages of this method include the easy preparation of a cheaper and environmentally safe catalyst system, a simple work-up procedure, and excellent catalytic efficacy.

Synthesis of Substituted 1-Benzyl-2H-1,2,3-Triazoles by a Click Reaction Using Calcium Carbide as an Acetylene Source

AbstractAn effective strategy for constructing substituted 1-benzyl-1H-1,2,3-triazoles was developed through click reactions of benzylic halides with sodium azide and calcium carbide as sources of nitrogen and acetylene, respectively. The advantages of this method are an easily handled inexpensive source of acetylene, a wide range of substrates, satisfactory yields, and simple workup procedures, which could promote the use of calcium carbide as a sustainable acetylene source in modern industrial chemistry.

Visible-light-mediated flow protocol for Achmatowicz rearrangement.

The batch processes of APIs/pharmaceutical synthesis are prone to suffer significant limitations, including longer process time, shortage of skilled manpower, laborious post-synthetic work-up, etc. To address the inherent limitations of batch processes, a novel approach was undertaken, resulting in the establishment and development of a visible light-assisted modular photo-flow reactor with a seamlessly integrated post-synthetic work-up procedure enabling the efficient synthesis of dihydropyranones from furfuryl alcohols. The reaction uses sun light as green energy source, and the novel photo-flow reactor platform developed with an integrated system enabling a downstream process in a time and labor-efficient manner which facilitates the Achmatowicz rearrangement, resulting in a fast (10 min) formation of the dihydropyranone products.

Nano-reusable CuO-ZnO Catalyzed One-Pot Synthesis of 1-Amidoalkyl-2-Naphthols under Green Condition

Introduction: The Developed CuO-ZnO nanocomposite has been demonstrated as a new and environmentally friendly catalyst for one-pot multicomponent reaction between aldehydes, 2- naphthol and amides in the synthesis of 1-amidoalkyl-2-naphthols. Method: The new catalyst was synthesized by a ball-milling method by mixing a mixture of CuO and ZnO powder in various proportions and characterized by different spectroscopic methods such as powder X-ray diffraction (pXRD), Scanning Electron Microscopy (SEM), UV-Visible analysis, EDAX elemental analysis and mapping. The advantages of the devised protocol include a green approach, simple work-up procedures, avoidance of hazardous solvents, and good to excellent yields. RE Sult: Evaluation of the catalyst performance in the synthesis of some 1-amidoalkyl-2-naphthols showed presentable results. Sixteen derivatives were synthesized in desirable yield by our new method (4a-4p). CuO-ZnO nanocomposite as a safe and efficient catalyst could be reused up to 5 runs for the synthesis of naphthol derivatives without any significant decrease in its potency. Conclusion: The High purity of the products and desirable yields are other points that make the present work more attractive.

Synthesis and investigation of photo-physical properties of fluorescent dyes obtained by the Knoevenagel condensation of mono-, di- or tri-formyl aromatic aldehydes and various CH-acid derivatives

Fluorescent dyes were constructed using the Knoevenagel condensation of the appropriate aldehydes and CH-acid derivatives. Aromatic aldehydes containing one, two or three formyl groups were used as substrates. Cyanoacetamide, ethyl cyanoacetate, benzoylacetonitrile and indan-1,3-dione play the role of CH-acid derivative. The appropriate aldehydes were obtained by the Duff formylation reaction. The dyes synthesis procedure was very simple. The condensation was carried out in water in the presence of NaOH, as the basic catalyst at room temperature, and the dyes were obtained in yields between 58-93%. The work-up procedure was very simple, and the products do not require any further purification. The great advantages of this synthetic procedure are its simplicity, cheapness, compliance with the rules of green chemistry and the fact that it efficiently leads to structurally complex fluorescent dyes. Twenty-three new compounds were obtained, eleven of which exhibited fluorescence in solution and four in the solid state. Taking into account the fluorescence quantum yield and the emission maximum value close to the NIR range, the dye constructed by condensation of indan-1,3-dione and methyl 3,5-diformyl-4-hydroxybenzoate meets the above-mentioned requirements (Φ=16%, λem= 660 nm) best. The dye with the highest value of Φ = 25% in solid is a derivative of cyanoacetamide and 3,4,5-trimethoxybenzaldehyde.

Functionalization of Graphene Oxide with Guanidine: Synthesis, Characterization and Catalytic Potential in Aldol and Knoevenagel Condensation Reactions

AbstractHerein, we synthesized guanidine functionalized graphene oxide nanocomposites referred to GO‐GN NCs using hummer's method. GO‐GN NCs was characterized using Fourier‐Transform Infrared Spectroscopy, Powder X‐ray Diffraction, Thermogravimetric Analysis, Raman Spectroscopy, Field Emission Scanning Electron Microscopy, Transmission Electron Microscopy, Brunauer‐Emmett‐Teller (BET) surface area analysis to confirm successful formation of GO‐GN NCs catalysts. The catalytic performance for GO‐GN NCs was evaluated for Knoevenagel and Aldol condensation reaction in aqueous medium at ambient condition and result shows that it could be used as a highly efficient, stable, and durable catalyst. In addition, it has another feature such as easy workup procedure, large substrate tolerance, high reaction yield, good recyclability, and environmental friendliness.

Synthesis and application of merrifield resin based supported ionic liquids as organocatalyst for the greener synthesis of bio-active triazoles

A green and highly efficient catalysts based on merrifield resin supported acidic ionic liquids (MRBT-SILs) were synthesized using merrifield resin (non-toxic and chemically inert) and benzothiazole. The application of MRBT-SILs for the greener synthesis of 1,2,4-triazole-3-thiones or 1,2,4-triazole-3-oxones from condensation of ketones and thiosemicarbazide or semicarbazide respectively in 60% ethanol under ultra-sonication was studied. The protocol so developed has many additional benefits compared to those reported in previous articles such as smooth reaction, use of alcohol as solvent, good yield, ambient temperature, an easy workup procedure, catalyst recyclability, and high atom economy, making it highly efficient for synthesis as it obeys green chemistry principles. Further, catalyst could be reused up to eight cycles without any loss of its catalytic activity.

Efficient bis(indoyl)methanes synthesis enabled by SnO2/SiO2 nanocomposite

This study focuses on the synthesis of SnO2/SiO2 nanocomposite materials using sol-gel method and investigates their role in the synthesis of bis(indoyl)methanes via the Friedel–Craft alkylation route. The results, based on TON and TOF, show that 15 wt % SnO2/SiO2 exhibits high production efficiency and greater stability, with yields reaching 91–93% within 80–93 min. The prepared catalysts were characterized using various analytical techniques. The XRD revealed a crystalline size of 25.05 nm. The TEM analysis indicated a reduced particle size of about 25–30 nm. The SEM reflected the porous nature of the material and EDS showed the constituent elements Sn, O and Si with 3.65, 54.93, and 41.44 atomic %, respectively. FT-IR identified the composite framework with bands at 3408, 1620, 1093, 806 and 631 cm−1. The NH3-TPD indicated the presence of both Lewis acidic and Bronsted acidic sites in the composite materials. The BET method revealed a specific surface area and average pore diameter of 331.5814 m2/g. The developed method offers several advantages, such as a simple workup procedure, high yield, nontoxicity, cleanliness, and the ability to recycle and reuse the catalytic materials three times without loss in catalytic activity. These findings demonstrate the potential of SnO2/SiO2 nanocomposites as efficient and environmentally friendly catalysts for the synthesizing bis(indoyl)methane derivatives.

Complications after fine-needle aspiration cytology and core-needle biopsy in benign head & neck neoplasms

IntroductionBenign neck masses are one of the most common causes of clinical consultation in head & neck (H&N) clinics. Fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) have become among the main strategies for the diagnostic work-up of palpable and non-palpable neck lumps. Moreover, numerous studies have established the safety, high diagnostic yield, and added value of image-guided H&N biopsies, which play an important role in diagnosis, staging, and treatment planning, and can obviate the need for surgery for many patients. Nonetheless, despite the success of both techniques, there is a lack of recent studies regarding their safety and associated complication rates. Material & methodA retrospective analysis was performed of prospective data on patients undergoing ultrasound-guided FNAC or CNB for benign H&N disease (e.g., salivary gland benign tumors, branchial cleft cyst, thyroglossal duct, cyst, lipoma, or neurinoma) between June 2016 and June 2021 in a tertiary university hospital. ResultsOverall, 192 patients were included (105 [54.7%] men and 87 [45.3%] women). The Kolmogorov-Smirnov test indicated that our data were normally distributed (p = 0.452). The mean age of enrolled patients was 54 ± 10 (range: 18–87). The anatomical site most commonly affected was a major salivary gland (74%). Regarding incidence and type of complications, nine (4.7%) patients experienced complications, infection being the most common problem. The risk of complications was highest in patients with branchial cleft cysts who had undergone FNAC (p = 0.028). Overall, the risk of complications was not associated with the type of technique (p = 0.603; OR: 0.942; 95% confidence interval = 0.245–3.624). ConclusionAccording to our results, FNAC and CNB are generally safe and reliable procedures in the diagnostic work-up of H&N lumps. Nevertheless, physicians should be aware of certain risks associated with these procedures.

An Improved and Efficient Practical Process for the Synthesis of Enantiomerically Pure Solifenacin Succinate as an Antimuscarinic Agent

Background: Solifenacin succinate is an active pharmaceutical drug molecule that is extremely effective in treating overactive bladder symptoms, such as urine incontinence, urgency, and frequent urination. The free base is yellow oil, and the salt solifenacin succinate forms yellowish crystals that are extremely stable and effective. Solifenacin is a very active antagonist due to its potent muscarinic M3 receptor antagonist characteristics. Furthermore, solifenacin is effective in the treatment of bowel syndrome (IBS) by blocking M3 receptors and a broad spectrum of bowel dysfunction. Objective: The objective of this study was to develop a practical and highly efficient scalable synthesis of enantiomerically pure solifenacin as an antimuscarinic agent. Methods: In this work, the Zn(OTf)2 catalyst was used to develop a novel, environmentally benign, high-yielding, and robust protocol for the synthesis of enantiomerically pure solifenacin succinate. Results: The synthesis of enantiomerically pure solifenacin succinate was achieved in seven steps using commercially available phenylethylamine and benzoyl chloride as the starting materials. We carried out the reaction optimization by treatment of (S)-1-phenyl-3,4-dihydroisoquinoline-2(1H)- carbonyl chloride and (R)-(-)-3-Quinuclidinolin in the presence of Zn(OTf)2 catalyst. Furthermore, the solifenacin-free base was treated with succinic acid to afford its corresponding salt. The highlight of this protocol is the use of 20 mol% Zn(OTf)2 catalyst for the first time. The readily available starting materials, robustness, easy operation, high yield, and low cost make the approach more attractive and highly applicable. Conclusion: In summary, we developed a novel Zn(OTf)2-catalysed environmentally benign, highyielding, and robust protocol for the synthesis of enantiomerically pure solifenacin succinate. The proposed strategy is highly cost-effective and avoids the use of hazardous and unsafe sensitive, strong bases as well as tedious work-up procedures. Effective synthesis was achieved using readily available starting materials and reagents. Thus, the protocol is highly efficient, compatible, and commercially viable for the synthesis of important solifenacin products.

Practical Synthesis of N-Anilinylphenothiazines Using a Cyclic Hypervalent Iodine Coupling Reagent

AbstractAn improved protocol for the synthesis of N-anilinylphenothiazines based on the coupling reaction of anilines with phenothiazines using cyclic iodine(III) reagent is presented. In the improved method, the product can be isolated and purified without using column chromatography, and the cyclic hypervalent iodine reagent can be quantitatively recovered by aliquot manipulation. The workup procedure presented here is simpler compared to previously reported ones, facilitating large-scale synthesis. The para-selective phenothiazination of nitrogen-containing heterocycles such as hydroquinoline, which is important in pharmacology, was also successfully performed.

Microwave and ultrasound-assisted green protocols for 5-methylthiazole induced Betti bases: molecular docking, in-silico pharmacokinetics, and anticancer activity studies

ABSTRACT Herein, we describe an efficient one-pot three-component microwave and ultrasound-endorsed approaches for synthesizing distinct 5-methylthiazole induced Betti bases (5-methyl-thiazol-2-ylamino-aryl-benzylnapthols) employing silica sulfuric acid (SSA, silica-OSO3H) as an active heterogeneous acid catalyst. The title compounds produced in good yields (86–95%) from naphthalen-2-ol, 5-methylthiazol-2-amine, and assorted aryl aldehydes; and structurally characterized by spectral and elemental analyses. A comprehensive comparative study of conventional, ultrasonic, and microwave-irradiated synthetic routes has been achieved by optimizing various reaction parameters. These new protocols provide several advantages, including the use of an inexpensive, non-toxic, and reusable catalyst. Additionally, they benefit from mild reaction conditions, short reaction times, and simple workup and purification procedures, thereby increasing their practicality. Furthermore, the synthesized compounds were evaluated for their anticancer potency against A-549 (lung cancer) and A-498 (kidney cancer) cell lines, with scaffold IVa demonstrating excellent (GI50 < 10 µg/mL) inhibitory activity against A-549. Additionally, molecular docking was performed to investigate potential binding interactions between ligands and proteins. Scaffold IVa exhibited the best docking with cancerous target proteins 1M17 (−8.9 kcal/mol) and 1M14 (−7.2 kcal/mol), thereby supporting our bio-activity studies.

MPC@But-SO3H a mesoporous heterogeneous organocatalyst in one-pot tandem synthesis of dihydroindeno[1,2-b]pyrrole derivatives

A sustainable, metal-free, and highly efficient protocol for the synthesis of dihydroindeno[1,2-b]pyrrole derivatives via a tandem one-pot three-component reaction in aqueous medium at room temperature using an effective and reusable mesoporous heterogeneous organocatalyst, MPC@But-SO3H has been developed. MPC@But-SO3H was easily synthesized using a melamine-based covalent organic polymer and 1,4-butane sultone. The organocatalyst was well characterized by numerous spectroscopic techniques such as Fourier Transform Infrared (FTIR), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS), Powder X-ray diffraction (PXRD), Scanning Electron Microscope (SEM), Energy Dispersive X-ray (EDX), elemental mapping, and Thermal Gravimetric (TG) analyses. The catalyst displayed excellent catalytic potential, high thermochemical stability, and reusability for up to eight catalytic cycles. It offered the title compounds in excellent yields (˃90%) in a short reaction time (9-14 min). The synthesized compounds were characterized through FTIR, 1H, and 13C Nuclear Magnetic Resonance (NMR), and the molecular structure of 2-(benzylamino)-3a,8b-dihydroxy-1-methyl-3-nitro-3a,8b-dihydroindeno[1,2-b]pyrrol-4(1H)-one (4a) was confirmed by the Single Crystal XRD (SC-XRD) analysis. The key features of the present protocol include the use of water as a green solvent, zero involvement of any metal, sustainable reaction conditions, easy catalyst recovery, and a simple work-up procedure. The calculations for green metrics parameters further supported the greenness and sustainability of the protocol.

One‐Step Construction of 9,10‐Diarylphenanthrenes Using Solid Calcium Carbide as an Alternative of Gaseous Acetylene

AbstractA convenient method for the construction of 9,10‐diarylphenanthrenes through one‐pot multicomponent reactions of iodoarenes, o‐bromobenzoic acids, and calcium carbide is described. A series of target compounds are efficiently synthesized via Csp2−H activation and the simultaneous construction of five C−C bonds. The salient features of this method are the use of inexpensive and easy‐to‐handle solid alkyne source as an alternative of flammable and explosive gaseous acetylene. Meanwhile the use of commercially available substrates, wide functional tolerance, and simple workup procedure are also advantage of this protocol. In addition, the corresponding products can also be synthesized on gram scale.

Synthesis and crystal structural analysis of bismuth phosphovanadate compounds: An eco-friendly and recyclable catalyst for green synthesis of imidazole derivatives

In this investigation, our primary objective is to synthesize and characterize a bismuth phosphovanadate compound Bi13V0.8-xBa0.1PxO21.55 isotype to γ-Bi2O3 of sillenite type and space group is I23. This compound serves as a catalyst for the environmentally friendly synthesis of imidazole derivatives. These derivatives are produced via the reaction of benzil, ammonium acetate, and aromatic aldehydes, yielding satisfactory yields ranging from 87 % to 96 %. The composite catalyst underwent thorough characterization using a variety of analytical techniques, including Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction analysis (XRD). The investigations revealed the excellent performance of this catalyst system. The findings revealed that this catalyst system exhibited excellent performance, offering advantages such as quick reaction time, high product yields, and a simple workup procedure. Moreover, the catalyst demonstrated high stability and could be recovered for at least five repeated runs, providing cost-effective benefits and aligning with principles of green chemistry. This method has the potential to serve as an environmentally friendly protocol for synthesizing other heterocyclic compounds.

Application of Experimental Design (DoE) to Improve a Very Dilute Workup Procedure

Application of Experimental Design (DoE) to Improve a Very Dilute Workup Procedure

Harnessing aerial oxygen as an oxidant for dehydrogenation of 2, 3-dihydroquinolones: An application to synthesis of 4-quinolone alkaloids

Reagent and catalyst-free dehydrogenation (aromatization) of 2, 3-dihydroquinolones under aerobic oxidation is reported. This protocol involves metal-free synthesis of 4-quinolones from easily accessible stating materials in mixture of xylenes as solvent at 130 °C for 3–6 days. No chromatography purification and workup procedures are not needed. The product solidified in pure state from the reaction mixture and unreacted starting material remain in solution. The yields are up to 95 %. This methodology will be accessible to synthesize some 4-quinolone alkaloids.

Exploration of thiosemicarbazone-quinolone hybrids over in-silico, antioxidant, and zebrafish embryo toxicity studies

In this study, we successfully synthesized a series of acetyl quinolone thiosemicarbazones (5a-d, 6a-d) using a simple work-up procedure yielding column-free products. The structures of the synthesized compounds were confirmed by various spectroscopic techniques, including 1H, 13C, and 2D NMR, along with FT-IR. Detailed 2D NMR analyses such as COSY, HSQC, and HMBC were also performed. The biological activities were evaluated through in-vitro, in-vivo, and in-silico studies. In-vitro antioxidant properties were assessed using radical scavenging assays, revealing significant activity for compounds 5b and 6b, likely due to the aromatic ring substitution in the thiosemicarbazide side chain. In-vivo zebrafish embryo toxicity studies indicated minimal toxicity for these compounds. Additionally, in-silico studies showed that compounds 5b and 6b have good binding energies for proteins 2C0U, 3NM8 and 2X08. Further the DFT study of HOMO and LUMO energy gap is small for 5b and 6b. These findings suggest that acetyl quinolone thiosemicarbazones are promising candidates for various biological applications due to their potent antioxidant activity and low toxicity.