Diazonium Research Articles

Dual-Probe SERS Nanosensor: A Promising Approach for Sensitive and Ratiometric Detection of Glucose in Clinical Settings.

Diabetes is a major global health concern, with millions of annual deaths. Monitoring glucose levels is vital for clinical management, and urine samples offer a noninvasive alternative to blood samples. Optical techniques for urine glucose sensing have gained notable traction due to their cost-effectiveness and portability. Among these methods, surface-enhanced Raman spectroscopy (SERS) has attracted considerable attention thanks to its remarkable sensitivity and multiplexing capabilities. However, challenges remain in achieving reliable quantification through SERS. In this study, an alternative approach is proposed to enhance quantification involving the use of dual probes. Each probe is encoded with unique SERS signatures strategically positioned in the biologically silent region. One probe indicates the glucose presence, while the other acts as an internal reference for calibration. This setup enables ratiometric analysis of the SERS signal, directly correlating it with the glucose concentration. The fabrication of the sensor relies on the prefunctionalization of Fe sheets using an aryl diazonium salt bearing a -C≡CH group (internal reference), followed by the immobilization of Ag nanoparticles modified with an aryl diazonium salt bearing a -B(OH)2 group (for glucose capture). A secondary probe bearing a -B(OH)2 group on one side and a -C≡N group on the other side enables the ratiometric analysis by forming a sandwich-like structure in the presence of glucose (glucose indicator). Validation studies in aqueous solutions and artificial urine demonstrated the high spectral stability and the potential of this dual-probe nanosensor for sensitive glucose monitoring in clinical settings.

In situ Diazonium Salt Formation and Photochemical Aryl-Aryl Coupling in Continuous Flow Monitored by Inline NMR Spectroscopy.

A novel class of diazonium salts is introduced for the photochemical aryl-aryl coupling to produce (substituted) biphenyls. As common diazonium tetrafluoroborate salts fail, soluble and safe aryl diazonium trifluoroacetates are applied. In this mild synthesis route no catalysts are required to generate an aryl-radical by irradiation with UV-A light (365 nm). This reactive species undergoes direct C-H arylation at an arene, forming the product in reasonable reaction times. With the implementation of a continuous flow setup in a capillary photoreactor 13 different biphenyl derivatives are successfully synthesized. By integrating an inline 19F-NMR benchtop spectrometer, samples are reliably quantified as the fluorine-substituents act as a probe. Here, real-time NMR spectroscopy is a perfect tool to monitor the continuously operated system, which produces fine chemicals of industrial relevance even in a multigram scale.

Regioselective Twofold Annulation of Propargyl Acetates.

The regioselective annulation of unsymmetrical alkynes has always been a focused research topic. A Pd-catalyzed double annulation of unsymmetrical alkynes (i.e., yne-acetates) with aryl diazonium salts for the synthesis of substituted naphthalene derivatives is developed. The process addresses intrinsic regioselectivity challenges in the annulations of unsymmetrical alkynes. Mechanistic investigations shed light on the crucial role of the acetate-directing groups in determining the regiochemical reaction outcome.

Scalable electrochemical grafting of anthraquinone for fabrication of multifunctional carbon fibers

Carbon fiber electrodes were prepared by grafting anthraquinone molecules via a scalable electrochemical approach which simultaneously increased interfacial and electrochemical capacitance properties. In this work, anthraquinone diazonium salts were synthesized and grafted onto carbon fiber tows at various concentrations. These modified fibers were subsequently evaluated mechanically and electrochemically to analyze their suitability in structural supercapacitors. Compared to control fibers, the grafted anthraquinone groups resulted in a 30% increase in interfacial shear strength (IFSS) and 6.6× increase in specific capacitance. Industry application was also a focus thus carbon fibers were also modified with in-situ generated diazonium salts to determine the applicability to an in-line industrial process. Specifically, potentiostatic functionalization of fibers with in-situ generated diazonium salts AQ-1 and AQ-2, showed 3× and 4.3× increase in specific capacitance, respectively, relative to unmodified carbon fiber (CF). We expect that implementing a scalable method to introduce a conductive and electrochemically active covalently bound surface chemistry layer onto carbon fiber exhibits a higher specific capacitance than carbon fiber grafted with most other small molecules reported in literature. This will open new avenues for manufacturing multifunctional and high-performance fibers with tailored properties for specific/targeted applications.

Three-Component Radical Cross-Coupling: Asymmetric Vicinal Sulfonyl-Esterification of Alkenes Involving Sulfur Dioxide.

A novel catalytic system for radical cross-coupling reactions based on copper and chiral Pyridyl-bis(imidazole) (PyBim) ligandsis described. It overcomes the challenges of chemoselectivity and enantioselectivity, achieving a highly enantioselective vicinal sulfonyl-esterification reaction of alkenes involving sulfur dioxide. This strategy involves the use of earth-abundant metal catalyst, mild reaction conditions, a broad range of substrates (84 examples), high yields (up to 97% yield), and exceptional control over enantioselectivity. The reaction system is compatible with different types of radical precursors, including O-acylhydroxylamines, cycloketone oxime esters, aryldiazonium salts, and drug molecules. Chiral ligand PyBim is identified as particularly effective in achieving the desired high enantioselectivity. Mechanistic studies reveal that copper/PyBim system plays a vital role in C─O coupling, employing an outer-sphere model. In addition, the side arm effect of ligand is observed.

A novel ACE2-Based electrochemical biosensor for sensitive detection of SARS-CoV-2

SARS-CoV-2 emerged in late 2019 and quickly spread globally, resulting in significant morbidity, mortality, and socio-economic disruptions. As of now, collaborative global efforts in vaccination and the advent of novel diagnostic tools have considerably curbed the spread and impact of the virus in many regions. Despite this progress, the demand remains for low-cost, accurate, rapid and scalable diagnostic tools to reduce the influence of SARS-CoV-2. Herein, the angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV-2, was immobilized on two types of electrodes, a screen-printed gold electrode (SPGE) and a screen-printed carbon electrode (SPCE), to develop electrochemical biosensors for detecting SARS-CoV-2 with high sensitivity and selectivity. This was achieved by using 1H, 1H, 2H, 2H-perfluorodecanethiol (PFDT) and aryl diazonium salt serving as linkers for SPGEs and SPCEs, respectively. Once SARS-CoV-2 was anchored onto the ACE2, the interaction of the virus with the redox probe was analyzed using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Aryl diazonium salt was observed as a superior linker compared to PFDT due to its consistent performance in the modification of the SPCEs and effective ACE2 enzyme immobilization. A distinct pair of redox peaks in the cyclic voltammogram of the biosensor modified with aryl diazonium salt highlighted the redox reaction between the functional groups of SARS-CoV-2 and the redox probe. The sensor presented a linear relationship between the redox response and the logarithm of SARS-CoV-2 concentration, with a detection limit of 1.02 × 106 TCID50/mL (50% tissue culture infectious dose). Furthermore, the biosensor showed remarkable selectivity towards SARS-CoV-2 over H1N1virus.

Transition Metal and Photocatalyst Free Arylation via Photoexcitable Electron Donor Acceptor Complexes:Mediation and Catalysis

AbstractVisible‐light‐activated organic reactions unlock novel avenues for complex molecular transformations, impossible under standard “thermal” conditions, which makes them powerful tools in the arsenal of synthetic chemistry. However, transition metal‐based or organic photoredox catalysts are often used to ensure productive absorption of visible light, which might be not desirable to medicinal chemistry and industry due to toxicity, low sustainability, and high cost of most photocatalysts. A more environmentally and economically benign approach is based on the formation of transient electron donor‐acceptor (EDA) complexes between two reagents or a reagent and an additive, that readily absorb visible light, acting as internal photosensitizers. Within the EDA complex‐based arylation strategies, chemical transformations are mediated by noncovalent interaction between two molecules, namely between electron‐poor aryl halides or their synthetic equivalents and electron‐rich nucleophilic reagents or additives. Moreover, besides stoichiometric EDA complexes between two molecules, EDA complex based organocatalysis can be achieved in certain cases through regeneration of the donor molecules in the course of the reaction. Photoexcitation of the EDA complexes induces a single electron transfer (SET) process to generate aryl radical species for the arylation step. This Review will focus on the state‐of‐the‐art EDA complex‐based arylation strategies utilizing aryl halides, aryldiazonium, diaryliodonium, arylsulfonium and arylphosphonium salts as reactants, published mainly in the last five years.

Synthesis, characterization, solvatochromic, computational and antibacterial studies of a series of new 4-imino-3-(2-heteroarylhydrazono)chroman-2-one dyes

Herein, 4-aminocoumarin was synthesized and reacted with some diazonium salts derived from substituted 2-aminothiazoles to produce corresponding new azo dyes. These newly synthesized compounds were fully characterized by FT-IR and NMR spectroscopies and mass spectral analysis. The results testified that the obtained products exclusively exist in the hydrazone tautomeric form both in solid and solution states, and no spectral evidence of an azo structure was detected. The visible absorption spectral changes of the dyes were also studied in acetic acid, ethanol, chloroform, acetonitrile, dimethyl formamide, and dimethyl sulfoxide in the region of 300–600 nm, and the results were discussed according to possible electronic transitions in the compounds. The visible spectral behavior of ethanol-water solutions (50:50, v: v) of the dyes was also examined at different pH values at ambient temperature. Furthermore, the geometries of the proposed azo and hydrazone tautomeric forms of the dyes were optimized at B3LYP/6-311++G (d, p) level of theory. DFT calculations have been performed to evaluate the stability of the proposed azo and hydrazone tautomeric forms of the prepared dyes both in the gas phase and in solution, and the outcomes were compared with spectroscopic findings. Besides, antibacterial activities of the dyes dissolved in DMSO were evaluated using the well diffusion method against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) bacterial strains.

Synthesis, Identification, Biological Evaluation of Seven-membered Heterocyclic Derivatives from 2,3-di Chloroaniline

This study?s focus was centered on the synthesis of heterocyclic compounds incorporating a seven-membered ring, specifically 1,3-oxazepine. The initial phase of the synthesis involved the preparation of azo compound (1) through the coupling of the diazonium salt of 2,3-dichloroaniline with 4-bromoacetophenone in an alkaline alcoholic medium. This was then succeeded by the reaction of azo compound (1) with 4-nitroaniline and 4-methoxyaniline in absolute ethanol, employing glacial acetic acid as a catalyst, resulting in Schiff base derivatives (2) and (3), respectively. Subsequent to this, Schiff base (2) was reacted with phthalic anhydride and maleic anhydride, as well as succinic anhydride, in a dehydrated benzene environment, leading to the formation of heterocyclic seven-membered compounds (4), (5), and (6), respectively. Finally, Schiff base (3) was subjected to reaction with phthalic anhydride and maleic anhydride, as well as succinic anhydride, in dry benzene, resulting in the synthesis of heterocyclic seven-membered compounds (7), (8), and (9) respectively. Each of these synthesized compounds underwent characterization through Fourier-transform infrared and proton nuclear magnetic resonance spectroscopic analysis, and the progress of reactions was monitored through Rf and thin-layer chromatography techniques. Melting points were recorded as part of the characterization process. In addition, an investigation into the biological activity of these compounds was conducted against both positive and negative bacterial strains.. KEYWORDS :Azo compounds, Oxazepine, Schiff bases.

Organic Photoredox Carbonylation of Arenediazonium under Mild Conditions

AbstractThe modular synthesis of diverse carbonyl compounds is at the heart of organic synthesis. An optimized protocol for photoredox carbonylation was developed that operates under milder conditions with mesitylacridinium as a photocatalyst. Arenediazonium salts were converted into benzoates (with alcohols), benzoic acids (with water), benzamides (with amines), and chlorides (with 1-butyl-3-methylimidazolium chloride) at 20 bar CO and 20 °C.

Correction to “Mechanisms for the Oxidative Addition of Palladium(0) Complexes to Arenediazonium Salts”

Correction to “Mechanisms for the Oxidative Addition of Palladium(0) Complexes to Arenediazonium Salts”

Photosensitizer-free, visible light-mediated heterogeneous gold-catalyzed cross-coupling of aryldiazonium salts with allyltrimethylsilane

An efficient visible light-mediated and heterogeneous gold-catalyzed cross-coupling of aryldiazonium tetrafluoroborates and allyltrimethylsilane has been developed. The photosensitizer-free cross-coupling reaction proceeds smoothly in MeCN under irradiation with blue LEDs at room temperature by using 10 mol% of SBA-15-supported triphenylphosphine-gold(I) complex [SBA-15-Ph3PAuCl] as catalyst and provides a general and practical route for the synthesis of allylarenes in moderate to good yields. This heterogenized gold(I) catalyst can be readily recovered via a simple filtration of the reaction mixture and recycled up to eight times without any significant loss of catalytic activity.

Visible-light-promoted Meerwein 3,4-diarylation of maleimides with electron-deficient diazonium salts

3,4-Diarylmaleimides are widely explored as structural fragments of natural products, bioactive substances and components of luminescent materials. The reaction of aryl diazonium salts with various maleimides under visible light irradiation was studied. It was found, that aryl diazonium salts with electron withdrawing substituents give 3,4-diarylmaleimides under visible light irradiation at room temperature in the presence of sodium trifluoroacetate under photocatalyst and transition-metal-free conditions in yields up to 54%.

Two-step Continuous-flow Synthesis of 1,2-dimethyl-3-methylsulfanylbenzene via Diazotization and Methanethiolation

Abstract: 1,2-Dimethyl-3-methylsulfanylbenzene is the key intermediate of topramezone. This work designed a two-step continuous-flow device to synthesize 1,2-dimethyl-3-methylsulfanylbenzene via diazotization and methanethiolation. The results showed that compared with the batch process, the continuous-flow method greatly shortened the residence time to 1 minute, avoided the accumulation of large amounts of diazonium salts to reduce decomposition and increased the product yield to 91.7%. At the same time, the continuous-flow process improved the safety and efficiency of the reactions, saved reaction time and had good prospects for industrial application.

Efficient Synthesis of Pyrido[3,4-c]cinnolines and Pyrido[3,2-c]cinnolines by Intramolecular Azo Coupling Reaction of 4,6-Diaryl-3-pyridine Diazonium Salts and Study of Their Antiviral Activity

AbstractA new method is proposed for the synthesis of pyrido[3,4-c]cinnolines and pyrido[3,2-c]cinnolines. Pyridine-3-diazonium tetrafluoroborates, containing donor methoxy groups in one of the aryl substituents, form pyridocinnolines at 0 °C by intramolecular azo coupling reaction. The 2′-methoxy group in the aryl substituent of the pyridine-3-diazonium salt participates in the aromatic nucleophilic substitution reaction, which results in the elimination of the diazo group to form benzofuro[2,3-c]pyridine and benzofuro[3,2-b]pyridine. The intermediate and target reaction products were isolated in high yields.

Synthesis of new azo compounds based on 4-aminosalicylic acid and study anti-corrosive activity

New azo dyes were prepared from 4-amino-2-hydroxy-benzoic acid in two steps; the first step includes preparation the diazonium salt. Then, diazonium compound coupled with different aromatic compounds containing donating groups (orcinol, 2,6-dimethylphenol, hydroquinone, catechol, 1,2,4-triazole, 2-methyl-naphthol and 4-toluidine, respectively). The physical properties of synthesized compounds were studied like melting point and solubility. The target molecules were characterized using FTIR, NMR and CHNS techniques. The activity of the compounds 1, 3 and 5 as anticorrosion on carbon steel in 0.5 M HCl solution was studied using weight loss method at different times and two concentrations (0.003 M, 0.005 M) of inhibitors at 298 K. Compound 5 showed more inhibition efficiency and less weight loss at different concentration in comparison with compound 1 and compound 3.
 KEY WORDS: Azo dye, 4-Aminosalicylic acid, Diazonium salt, Anti-corrosion
 Bull. Chem. Soc. Ethiop. 2024, 38(2), 473-479. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i2.14

Synthesis, characterization and theoretical aspects of copper and zinc divalent ion complexes with azo dye derived from 4,5-diphenylimidazole

Azo dye ligand derived from 4,5-diphenyl imidazole and 4,4-diaminodiphenylmethane was synthesized by diazomium coupling reaction. In this reaction an amine (4,4-diaminodiphenylmethane was converted to the diazonium salt and coupled with 4,5-diphenyl imidazole. The bright coloured Cu(II) and Zn(II) complexes with this ligand were synthesized by refluxing the latest with both metals chloride salts. The prepared compounds were characterized by 1H-NMR, 13C-NMR, FTIR, UV-Visible, molar conductivity and atomic absorption. By the infrared data, the coordination between copper and zinc ions and the azo ligand achieved through the nitrogen of the azo group and one of the nitrogen atoms in the imidazole ring. By the molar conductivity test, the non- electrolytic nature of both complexes was also confirmed. The suggested structure for these complexes is octahedral. Using density functional theory (DFT) some theoretical data was obtained for the synthesized complexes. The obtained data include the highest occupied and the lowest unoccupied molecular orbitals energy (HOMO and LUMO), electron density, thermodynamic functions (ΔG°, ΔS°, ΔH°, ΔE°), ionization potential (IP), electron affinity (EA), electrophilicity(ὠ), electronegativity (En), chemical hardness (η) and dipole moment (μ). According to these studied parameters some properties of the two complexes were explained and discussed.
 KEY WORDS: Cu(II) and Zn(II) complexes, Azo ligand, 4,5-Diphenylimidazole, 4,4-Diaminodiphenylmethane, Theoretical study
 Bull. Chem. Soc. Ethiop. 2024, 38(2), 313-323. 
 DOI: https://dx.doi.org/10.4314/bcse.v38i2.4

Investigation of solvatochromic, optical, organic field effect transistor (OFET), antibacterial, and molecular bonding of some azothiazolidine-2,4-dione (AZO-TZD) dyes

Here, new AZO-TZD derivatives (1−11) were synthesized using cellulose sulphuric acid (CSA) as a catalyst to prepare diazonium salts and Knoevenagel condensation to produce final products. The prepared dyes were characterized by various methods including UV–Vis, FT-IR, MS, NMR spectroscopic techniques, X-ray diffraction analysis (XRD) and elemental analysis to perform detailed structure elucidation. Then, in another attempt, solvatochromic absorption was studied using different solvents. Also, the effects of substituent with electron-withdrawing and electron-donating groups at their o-, m-, and p-position were investigated. To access a deeper understanding of molecular properties, computational analysis of molecular geometry, optoelectronic properties, and ionization potential was performed. The purpose of the calculations is to clarify the role of different solvents, substituents and donor and acceptor characteristics of the connected rings in the synthesized compounds. Analysis of the UV–Vis spectrum confirmed that these molecules have acceptor–donor-acceptor characteristics that resemble an organic field effect transistor (OFET).In other efforts to evaluate their use as antibacterial, anticancer and anti-Alzheimer agents and their interaction with four different types of enzymes, such as carotenoid dehydrosqualene synthase (PDB ID: 3ACX, gram-positive), aromatase (PDB Id: 4GL7) and acetylcholinesterase (PDB) Id: 7AIX), through UDP-3-O-Acyl-N-Acetylglucosamine Deacetylase (PDB ID: 5U39, gram-negative) and their anticancer docking calculations were investigated.

Controlled surface functionalization using aryldiazonium salts with bulky protecting groups for the development of DNA-based sensing platforms

Developing a comprehensive procedure for tuning the surface and interfacial properties of DNA biorecognition interfaces is crucial for a wide range of analytical applications, but proves to be a difficult task. This study aims to address the challenge by exploiting the significant advantages of surface grafting with protected aryldiazonium salts and “click” azide-alkyne functionalization reactions. In order to control the surface density of reactive alkyne moieties over a wide range, suitable for the immobilization of large biomolecules, we explored novel protecting groups such as triphenylsilyl (TPS) and tris(biphen-4-yl)silyl (TBPS), which are bulkier than the triisopropylsilyl (TIPS) group employed in previous studies. We prepare phenylethynyl-grafted glassy carbon substrates using a two-step protocol consisting in electrografting with the corresponding silyl-protected diazonium salt, followed by nucleophilic cleavage of the protecting group. Using appropriate derivatization reagents and a combination of electrochemical and surface analytical techniques, we find a strong correlation between the protecting group size and the surface coverage of phenylethynyl groups. Next, using the phenylethynyl-grafted substrates for the immobilization of an azide-modified cocaine/quinine aptamer as model bioreceptor, we demonstrate that the surface density of ssDNA decreases with increasing size of the protecting group employed in the grafting procedure. Finally, we prove that our strategy can be effectively employed to fine-tune the analytical performance of an aptasensing platform for quinine detection.

Synthesis of novel azo pyrazole disperse dyes for dyeing and antibacterial finishing of PET fabric under supercritical carbon dioxide

Supercritical carbon dioxide (scCO2) has been suggested as a good substitution to environmentally harmful water-based tincturing. The present study describes the successful synthesis of some biologically active dispersion tinctures for supercritical carbon dioxide tincturing of polyester fabric. The coupling of 1-cyanoacetylpiperidine (1) with the diazonium salt of aryl amine derivatives (2a–d) produced 1-((aryldiazenyl) cyanoacetyl piperidines (3a–d). To create the derivatives of 4-(phenyldiazenyl)-5-(piperidin-1-yl)-1H-pyrazol-3-amine (5a), the propane nitriles (3a–d) were condensed with hydrazine hydrate. However, the unexpected 3-aminopyrazol-5-ol yellow–red dispersion dyes (4a–d) were identified as the reaction results. The MS, IR, and NMR spectra were used to describe the novel dyes, and the results exactly matched the suggested structures. The antibacterial test, which was conducted using the AATCC method, revealed that some of the compounds (3a–d) and (4a–d) had impressive antibacterial capabilities against the researched +ve and gram −ve bacteria. For eight dyestuffs, the dyeability, color strength, and color fastness of the tincturing process were evaluated. The evaluation focused on determining color uptake using a gauge for color strength (K/S). All dyes displayed excellent rubbing, washing, and light fastness (color change and staining grade of 4–5).