Diazonium Research Articles

Synthesis of N‐Phenylazo (Triazine) Derivatives of 6‐Aminouracil Using Diazonium Salt Under Catalyst‐Free Condition

AbstractIn the current study, for the first time, N‐phenylazo (triazine) derivatives of 6‐aminouracil compounds were produced at room temperature under catalyst‐free conditions in pyridine using an easy, efficient, and green process. The main advantages of this approach are that it doesn't require a catalyst, is inexpensive, eco‐friendly, non‐toxic, and simple to handle. This technique shows a broad range of substrate compatibility for uracil compounds and diazonium salts.

A New Contribution Confirming the Analogy Between NO+ and Related Aryldiazo Ligands

Abstract. The reaction of the cyclometalated five‐coordinate 16 electron iridium(III) complex [IrCl(H){P(tBu)2C6H4‐k2P,C}{P(tBu)2Ph}] (1) with the diazonium salt [p‐BrC6H4N2]BF4 in dichloromethane at room temperature was investigated. By spontaneous reductive elimination the iridium(I) complex salt trans‐[IrCl(N2C6H4Br‐p){(P(tBu)2)Ph}2]BF4 (2) was obtained in good yield. Therefore, this observed reaction behavior exhibits the diazonium unit as a strong p‐acceptor group and confirms furthermore the analogy between nitrosyl and aryldiazonium ligands. The new compound 2 has been characterized by standard spectroscopic methods and the molecular structure of 2 was determined by a single‐crystal X‐ray diffraction analysis (monoclinic, space group Cc, Z = 4).

Selective Coupling of β-(Borylvinyl)silanes by a Gold-Catalyzed Hiyama Reaction-An Easy Way to Diaryl-Substituted Vinyl Boronates.

The use of diaryl-substituted vinyl boronates, a class of chemical building blocks with well-known synthetic utility, is principally limited by the difficulty faced in their preparation. Herein, we present a convenient synthetic strategy based on a gold-catalyzed Hiyama arylation of (Z)-β-(borylvinyl)silanes, which are easily accessible by hydroboration of silylalkynes. By exploiting the highly electronegative nature of the gold(III) intermediate (which is accessed by light-assisted oxidation using aryl diazonium salts), a selective activation of the silyl group in the presence of the boron moiety is achieved. This opens a route to selectively synthesize diaryl-substituted vinyl boronates. The reaction shows a broad substrate range, excellent functional group tolerance, and perfect chemoselectivity. Experimental studies and density functional theory (DFT) calculations allowed us to elucidate the mechanism of the reaction. The synthetic potential was demonstrated by downstream transformations providing a facile route to bifunctional phenanthrenes and triaryl-substituted olefins.

A Precise Route to Tetrasubstituted Allyl Amines via Regioselective Dicarbofunctionalization of Masked Propargyl Amines.

Allyl amines are vital components in various biologically important molecules and play a significant role in their function. Presently, most methods are geared toward the preparation of di- and trisubstituted allyl amines, leaving a gap for the development of more versatile approaches. We herein describe an approach to yield tetrasubstituted allyl amines through palladium (Pd)-catalyzed regioselective dicarbofunctionalization of masked N-phthalimide-protected propargyl amines. The cationic Pd-intermediate in conjunction with the masked amine exerts collective control for the reaction regioselectivity. This method accommodates a wide range of alkynes, aryl boronic acids, and aryl diazonium salts offering direct access to a wide range of unusual tetrasubstituted allyl amines.

Synthesis of 1,3,5-trisubstituted 1,2,4-triazoles enabled by a gold-catalyzed three-component reaction

Valuable fully substituted 1,2,4-triazoles are obtained via a gold-catalyzed three-component reaction involving ethyl diazoacetate, aryldiazonium salts, and nitriles. The reaction proceeds under mild conditions, is regioselective, and allows the introduction of mono- and di-substituted aryl rings at the ortho, meta, and para positions. Mechanistic evidence suggests the participation of Au(III) species as the active catalysts.

Radical Cyclizations of N‐Methylallyl‐2‐arylindoles with Polychloromethanes to Assemble Polychloroalkylated Indolo[2,1‐a]isoquinolines

AbstractAn efficient synthesis of polychloroalkylated indolo[2,1‐a]isoquinolines has been achieved via aryldiazonium salt induced radical cyclization reaction of N‐methylallyl‐2‐arylindoles with dichloromethane or trichloromethane. In this reaction, neither metal catalyst nor additional oxidant was required, and an isoquinoline ring was constructed by tandem radical additions on the nonactivated carbon‐carbon double bond of allyl group in 2‐arylindoles. This protocol features advantages of wide substituent scope, environmentally friendly conditions and good yields.

Developing a New Method for the Estimation of Valsartan (VST) in Pharmaceutical Dosage Samples by Using Diazotization and Coupling Reactions Spectrophotometrically

Introduction: A new method for valsartan (VST) estimation in pharmaceutical dosage samples by spectrophotometry was developed. Method: The method was based on the formation of coloured dye by the diazotization reaction of 3-amino-2-naphthol with sodium nitrite in an acidic medium to form diazonium compounds, which were then coupled with VST in a basic medium. Results: The drug sample showed linearity in the range 4.6 - 24.2 μgmL-1, and the λmax was found at 432nm. Sandell’s sensitivity (9.950×10-3), Molar absorbtivity (Ɛ= 4.377×104), regression equa-tion (y= 0.0775x + 0.0041), correlation coefficient (r2= 0.968), detection limit (DL= 0.668) and quantitation limit (QL= 2.024) were evaluated. Conclusion: The percentage recovery of the drug samples was found to be 100%. This method successfully determined VST in Pharmaceutical dosage samples.

Synthesis, Characterization, DFT Calculations, and Pharmacological Activity of Azo Dye Ligand and Its Cu(II) Complex Comprising Nitrogen and Oxygen Donor Atoms

ABSTRACTCoupling the diazonium salt of sulfadiazine with dibenzoylmethane afforded the 4‐(2‐(1,3‐dioxo‐1,3‐diphenylpropan‐2‐ylidene)hydrazinyl)‐N‐(pyrimidin‐2‐yl)benzene sulfonamide ligand (HL). The ligand (HL) and its Cu(II) complex structure have been investigated via magnetic attraction testing, TGA, FTIR, UV–visible, XRD, and CHN analyses. The spectrum data indicate that the ligand demonstrates monobasic bidentate behavior via deprotonating opposite the oxygen atom of the carbonyl (CO) group and linking using the NH of the hydrazone group (NNH). Copper (II) complex present in octahedral structure. A number of TGA steps (Ea, A, ΔH*, ΔS*, and ΔG*) had their dynamical characteristics computed and described using the Coats–Redfern and Horowitz–Metzger formulas. Molecular studio programmer was utilized to perform density functional theory (DFT) calculations in order to investigate the ideal configuration of HL and its Cu(II) complex. The HL and its copper (II) complex exhibited antitumor effects against MCF‐7 and HepG‐2 cell lines. Furthermore, the width of the inhibition zone was employed to evaluate the in vitro antibacterial effect of HL and a specific complex towards Gram‐negative organisms Escherichia coli (E. coli) and Gram‐positive organisms Staphylococcus aureus. The ligand and its Cu(II) complex were examined using both the viscosity and spectrum of absorption of calf thymus DNA binding experiments.

Development of microfibrillated cellulose-reinforced carboxymethyl cellulose dipstick imprinted with benzotrifluoride-bearing hydrazone sensor for colorimetric detection of organophosphonate.

The colorless and odorless nerve agents can cause paralysis and even death. The development of novel composite-based microporous strips has allowed for the rapid and visual detection of diisopropyl phosphorofluoridate (DIPF) nerve agent mimics. The active methyl-containing tricyanofuran and 4-aminobenzotrifluoride diazonium salt were azo-coupled in a straightforward manner to produce a new benzotrifluoride (BFT)-comprising tricyanofuran (TCF) hydrazone colorimetric probe. The molecular structure of the benzotrifluoride-bearing hydrazone (BFTH) was explored by different spectroscopic techniques. Microfibrillated cellulose (MFC) was produced using a green process from sugarcane bagasse, an agriculture waste that is notorious for being a solid pollution. Consequently, discovering a straightforward procedure to convert bagasse into valuable materials has been of utmost importance. MFC displayed diameters of 0.25-2 μm, whereas the sensory films exhibited pore diameters of 0.5-2.25 μm. Various quantities of the BFTH chromophore were used to create benzotrifluoride-bearing hydrazone/microfibrillated cellulose/carboxymethyl cellulose (BFTH/MFC@CMC) composites. The absorbance band of the hydrazone-immobilized composite increased from 435 nm to 580 nm as the content of DIPF was raised. When exposed to DIPF, the dipstick color shifted from orange to pink, according to the CIE Lab measurements. The sensor strip showed a detection limit to DIPF between 5 and 200 ppm.

The Prospect of Improving Pancreatic Cancer Diagnostic Capabilities by Implementing Blood Biomarkers: A Study of Evaluating Properties of a Single IL-8 and in Conjunction with CA19-9, CEA, and CEACAM6.

Background/Objectives: This study aims to evaluate the possible clinical application of interleukin 8 (IL-8) as a single biomarker and its capabilities in combination with carbohydrate antigen (CA19-9), carcinoembryonic antigen (CEA), and carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as diagnostic and prognostic tools for pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 170 serum samples from patients with PDAC (n = 100), chronic pancreatitis (CP) (n = 39), and healthy individuals (n = 31) were analysed. IL-8 and CEACAM6 were measured by an enzyme-linked immunosorbent assay (ELISA). CA19-9 and CEA were determined by chemiluminescent microparticle immunoassay, and bilirubin was quantified using a diazonium salt reaction. Receiver operating characteristic curve analysis, logistic regression, and Kaplan-Meier analyses were performed to evaluate the properties of a single IL-8 and in combination with other biomarkers. Results: The concentrations of IL-8 were statistically significantly higher in the PDAC group compared to the CP and control groups. Heterogeneous levels of IL-8 correlated with PDAC stages (p = 0.007). IL-8 had good and satisfactory diagnostic efficacy in differentiating PDAC from controls (0.858; p < 0.001) and patients with CP (0.696; p < 0.001), respectively. High and low expressions of IL-8 were not significantly associated with overall survival (OS) or disease-free survival (DFS). A combination of IL-8, CEACAM6, and CA19-9 reached the highest AUC values for differentiating PDAC from the control group. The best classification score between PDAC and the control group with CP patients was obtained by merging IL-8 and CA19-9 (0.894; p < 0.001). Conclusions: These results provide compelling evidence of IL-8 as a promising diagnostic biomarker. Nonetheless, due to the high complexity of PDAC, only the conjunction of IL-8, CA19-9, and CEACAM6 integrates sufficient diagnostic capabilities.

Demonstrating Synergistic Activity of Magnetic Iron Oxide Nano Photocatalyst for C-H Activation in Heterogeneous Phase.

This report describes a dual catalytic approach for the versatile C‒H arylation of arenes under photo-excitation at room temperature. The cooperative catalysis utilizes iron oxide magnetic nanoparticles (which mostly contain Fe3O4 along with some γ-Fe2O3) as the potential photocatalyst, which merges with the Pd-catalyzed C‒H activation cycle for the reductive generation of aryl radical from aryl diazonium salt, revealing its photocatalytic activities. The method is applicable to a wide range of aryl coupling partners and different directing groups, demonstrating excellent productivity, nice co-operativity and recyclability. Adequate control experiments and mechanistic studies assisted in establishing the radical-based mechanism for the C‒H arylation occurring in the heterogeneous phase.

Spectrophotometric determination of metoclopramide hydrochloride in pharmaceutical tablets, by diazotization-coupling method with 1-naphthol as the coupling agent

Simple, rapid and sensitive spectrophotometric method was proposed for the analysis of metoclopramide hydrochloride (MPH) in pure form as well as in pharmaceutical tablets. The method is based on the diazotization reaction of MPH with sodium nitrite in hydrochloric acid medium to form diazonium salt, which is coupled with 1-naphthol in sodium hydroxide medium to form azo dye, showing absorption maxima at 550 nm. Beer’s law is obeyed in the concentration range of 0.4 – 18 µg mL-1 of MPH with detection limit 0.5448 µg mL-1. The molar absorptivity and Sandell’s sensitivity are 3.4969 × 104 L mol-1 cm-1 and 0.0101 µg cm-2, respectively. The method was successfully applied to the determination of MPH in pharmaceutical tablets without any interference from common excipients used as additives in tablets. The results agree favorably with the official British Pharmacopoeia method.

Synthesis and characterization of some new Schiff base azo disperse dyes based on chromene moiety for simultaneous dyeing and antimicrobial finishing

New azo Schiff base disperse dyes based on a chromene moiety were synthesized by reacting (2-amino-7-hydroxy-4-(4-methoxyphenyl)-4 H-chromene-3 carbonitrile) and(2-amino-4-(3,4-dimethoxyphenyl)-7-hydroxy-4 H-chromene-3-carbonitrile), with vanillin and ninhydrin, producing new chromene Schiff base derivatives, which in turn were coupled with 2-chloro-4-nitroaniline diazonium salt to give new 4 azo disperse dyes (1–4). The structures of the prepared dyes were confirmed using elemental analysis, 1HNMR spectroscopy, mass spectrometry, and IR. The synthesized dyes were applied to polyester and nylon fabrics using different dyeing techniques: high temperature- high pressure, and ultrasonic dyeing methods. The highest K/S values for all investigated dyes were achieved usinga high temperature-high pressure dyeing technique. Also, the color reflectance of all synthesized dyes with different dyeing shades (1%, 2%, and 3%) was obtained. The fastness properties of the dyed samples using the investigated dyes showed good color fastness toward light, washing, rubbing, and perspiration fastness. The presence of a chromene moiety and Schiff base in the investigated dyes promotes a higher antimicrobial activity on nylon and polyester fabrics against all tested bacteria (E. coli gram-negative and Staphylococcus aureus gram-positive) and two fungi, Aspergillus Niger and Candida albicans.

Synthesis of Aryl Alkyl Thioethers via a Copper-Catalyzed Three-Component Reaction with DABSO, Aryldiazonium Salts, and Alkyl Bromides.

We developed a method for synthesizing aryl alkyl thioether compounds via a three-component reaction involving aryldiazonium salts, 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide), and alkyl bromides. Optimal yields were achieved when a copper catalyst was used in conjunction with zinc and tetrabutylammonium bromide in an acetonitrile solvent at 130 °C for 10 h. This methodology demonstrates good functional group tolerance and enables the successful synthesis of various aryl alkyl thioethers with moderate to high yields.

Electrochemical grafting of diazonium salts on silica-terminated versus H-terminated silicon

Diazonium salts are one of the most widely used molecules for functionalising electrode surfaces, due to their high reactivity toward a range of different electrodes but have mostly been studied on carbon and gold. Recent work has demonstrated that diazonium salts can be reduced on silica-terminated silicon (Si/SiOx) despite silica (SiOx) being an electrically insulating material, but this interesting phenomenon was only demonstrated on one specific crystal orientation, Si(111) using specific diazonium salts molecules – a more complete understanding of the electrochemical properties of these silica-terminated silicon electrodes remains unclear. In this work, we develop a thorough understanding of the reduction of diazonium compounds on silica-terminated silicon using silicon with different crystal orientation and using nano-structured silicon surfaces that are chemically etched to simultaneously expose different crystal orientations. A comparison between the reduction process on oxide free silicon (Si–H) and silica-terminated Si is then made to reveal the effect of the crystal orientation (amorphous vs crystalline) and the insulating nature of the distal surface (Si‒H vs SiOx) on the reduction process. Results show that diazonium salts form, well-packed thin films on silica-terminated silicon regardless of the crystal orientation of the silicon. The rate of diazonium reduction was found to be sensitive to the crystal orientation of Si only when the diazonium salts are in direct contact with the crystal plane (i.e. in contact with Si–H) as opposed to when there is a thin layer of native amorphous oxide material in between. The reduction rate is sufficiently slow on silica-terminated silicon that at slow scan rates, the system reaches a steady state current and become diffusion controlled. This is not observed on oxide-free silicon electrodes which are observed to be governed by a kinetically driven mechanism. These findings deepen our understanding of the electrochemical activity of silica-terminated silicon surfaces which are widely used in solar cells, electronics, chemical and biosensors.

A “sizing-free” strategy to improve the interfacial property of PEEK/CF composites based on “grafting-bridging” bifunctional diazonium salt

Achieving simple and efficient interfacial modification between carbon fiber and polyether ether ketone (PEEK) has been the pursuit of researchers. In this study, by comparing the nucleophilicity of various aromatic amines, a direct Schiff base reaction with polyether ether ketone (PEEK) has been achieved. Based on this, a “grafting-bridging” bifunctional diazonium salt containing a phenylethylamine structure was designed and synthesized to enhance the interfacial strength through covalent bonding without the use of sizing agents. The diazonium salt was grafted onto the surface of carbon fiber through electrochemical reduction, while the PEEK resin and phenylethylamine could achieve bridging through heat treatment, thus a PEEK/CF interface with enhanced covalent bonds was constructed. The reaction and conversion rate between phenylethylamine and PEEK resin were confirmed through IR and NMR. The successful grafting of the diazonium salt on the carbon fiber was determined through XPS and cyclic voltammetry. The bridging reaction on the surface of carbon fiber was verified through XPS and the use of 6F-PEEK with characteristic elements. As a result, the interfacial shear strength (IFSS) of the modified PEEK/CF interface reached 86.2 MPa, representing a 102.8 % improvement compared to the untreated interface of 42.5 MPa, fully demonstrating the excellent effect of the bifunctional diazonium salt.

Computationally Optimized Graphene-Based Electrochemical Sensor with Enhanced Signal Stability for the Determination of the Antimicrobial Agent 9-aminoacridine

A hydrophobic aryl diazonium salt has been synthesized from 3,5-bis(trifluoromethyl)aniline and utilized to covalently modify graphene nanoplatelets and carbon nanotubes. The modified nanomaterials were applied on a screen-printed electrode/ion sensing membrane interface resulting in reduced potential drift to 100 μV h−1 compared to control sensors. Characterization was achieved through X-ray photoelectron spectroscopy. The electrode’s response was optimized using response surface methodology and then utilized for determination of 9-Aminoacridine (9-AA) in pharmaceutical gel dosage form and spiked human plasma without prior extraction steps. 9-AA is a fluorescent dye with antimicrobial activity that eradicates a range of microorganisms that can cause oral sores or broken skin and it has been recently used as anticancer among other uses as fluorescent dye and pH indicator. Accurate determination of 9-AA could help in adjusting dosages for each application. The optimized sensor was validated per IUPAC guidelines and obtained a wide linearity range from 1.0 × 10–7 M to 1.0 × 10–2 M, correlation coefficient of 0.9997, improved Nernstian slope 59.72, long term stability, and lower limit of detection (9.0 × 10–8 M). Furthermore, Analytical Eco-scale and AGREE methods were utilized to evaluate the presented method’s greenness.

Nano-synthesis, characterization, theoretical, biological and catalytic studies of Mn(II), Cu(II), Cd(II), and Th(IV) complexes based on antipyrine azo dye ligand

The design and detailed characterization of the azo dye ligand obtained from the reaction of 4-aminoantipyrine diazonium salt with 3-hydroxybenzaldehyde (HL) and its novel metal chelates with Mn2+, Cu2+, Cd2+ and Th4+ ions have been presented. Utilizing modern spectroscopic and analytical techniques, these complexes were found to adopt an octahedral geometry, demonstrate inner sphere d2sp3 hybridization for Th(IV) complex and outer sphere sp3d2 hybridization for other complexes. Particle sizes calculated using the Debye-Scherrer equation on XRD patterns were 32.05 nm for Mn(II), 34.07 nm for Cu(II), 30.90 nm for Cd(II), and 22.05 nm for Th(IV). These substances' anticancer activity was assessed on human lung cancer cells (A-549) and pancreatic carcinoma cell lines (PANC-1). Cd(II) complex exhibited higher cytotoxicity against the A-549 cell line than the reference drug vinblastine sulfate which revealing its potential application as a new anticancer agent. Quantum chemical computations using the DMOL3 module's density functional theory (DFT) and molecular docking studies with the Schrödinger suite demonstrated significant inhibitory effects of the free organic compound and Cu(II) chelate on the FGFR1 protein, crucial for cell development and differentiation. Additionally, the study examined the catalytic activity of HL and its metal chelates in the oxidative degradation of methyl violet 2B dye in presence of H2O2. The order was followed by the pseudo-first-order rate constants: Th(IV) chelate (0.9556 min⁻¹) > HL (0.4911 min⁻¹) > Cu(II) chelate (0.5979 min⁻¹) > Mn(II) chelate (0.2645 min⁻¹) > Cd(II) chelate (0.2280 min⁻¹).

Interactions of novel 1,3-diaryltriazene-sulfamethazines with carbonic anhydrases: Kinetic studies and in silico simulations

Sulfonamides, recognized as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, are crucial in treating diverse diseases, including epilepsy, glaucoma, bacterial infections, and various pathological processes, e.g., high blood pressure, rheumatoid arthritis, ulcerative colitis, pain, and inflammation. Additionally, therapeutically, 1,3-diaryl-substituted triazenes and sulphamethazines (SM) are integral components in various drug structures, and the synthesis of novel compounds within these two categories holds substantial significance. Herein, ten 1,3-diaryltriazene-substituted sulphamethazine derivatives SM(1-10), which were created by reacting the diazonium salt of sulphamethazine with substituted aromatic amines, were synthesized and the physiologically and pharmacologically relevant human (h) isoforms hCA I and II, cytosolic isozymes, were included in the study. The synthesized compounds showed excellent inhibition versus hCAs; the 4-butoxy (SM7, KI of 5.69 ± 0.59 nM) compound exhibited a potent inhibitory effect against the hCA I compared with the reference drug acetazolamide (AAZ, KI of 116.00 ± 8.48 nM). The 4-cyano (SM4, KI of 5.87 ± 0.57 nM) compound displayed higher potency than AAZ (KI of 57.25 ± 4.15 nM) towards hCA II. Meanwhile, among the synthesized molecules, the 3,4-dimethoxy (SM9, KI of 74.98 ± 10.49 nM, SI of 9.94) compound (over hCA I) displayed a noticeable selectivity for hCA isoform II. The target compounds in the molecular docking investigation were determined to take part in various hydrophilic and hydrophobic interactions with nearby amino acids and fit nicely into the active sites of the hCAs. This research has yielded compounds displaying varying affinity toward hCA isoenzymes, ultimately serving as potent and selective hCA inhibitors. Given its substantial biological inhibitory potency, this particular derivative series is determined to hold the potential to serve as a promising lead compound against these hCAs.

A one-pot strategy for modifying the surface of Ti3C2Tx MXene

Surface modification of MXenes significantly expands their potential for a wide range of applications. Here, we demonstrate a one-pot spontaneous polymerization of acrylic acid onto MXene sheet surfaces using an aryl diazonium coupling agent (nitrobenzene diazonium salt) as an approach to tune MXene interfacial properties. We use this formation of polymer coatings as a coagulation strategy for spinning fibers from liquid crystal MXene dispersions, obtaining densified free-standing fibers with tensile strength and breaking energy of ~155 MPa and ~4.5 MJ m−3. This simple method potentially offers a scalable approach for fabricating functional MXene macroarchitectures.