N-bromosuccinimide Research Articles

Metal free, one pot 1,6-Conjugate Addition of Diol on para-Quinone Methide followed by ipso cyclization: An Approach to Spiro 1,4-Dioxane cyclohexadienone Derivatives.

A novel one-pot transition metal-free and Brönsted acid mediated 1,6-conjugate addition of bisnuleophilic diol on biselectrophilc para-quinone methide followed by ipso cyclization assisted by NBS has been developed under mild reaction conditions, offers a new approach to synthesize spiro 1,4-dioxane cyclohexadienone derivatives. This strategy features broad substrate scope of p-QMs with high functional group tolerance and good yields of spirocyclic scaffolds (60-92 %). N-Bromo succinimide an important role in an ipso spirocyclization with high efficiency.

Cover Feature: Brønsted Acid versus Phase‐Transfer Catalysis in the Enantioselective Transannular Aminohalogenation of Enesultams (Chem. Eur. J. 62/2022)

Alice points out the preference of one conformational enantiomer by “crossing the mirror” thanks to the catalyst formed from the phosphoric acid and bromine “delivered” by N-bromosuccinimide (NBS). Both the selected conformer and the new catalyst formed in situ merge their respective roads to converge on the product. More information can be found in the Research Article by U. Uria, P. Merino, J. L. Vicario, and co-workers (DOI: 10.1002/chem.202202267).

SiO2-supported HClO4 catalyzed synthesis of (Z)-thiazolylhydrazonoindolin-2-ones and their electrochemical properties

In this paper, an environmentally benign silica-supported perchloric acid (HClO4–SiO2) catalyzed green FCDR strategy has been developed for the synthesis of (Z)-THIs (6) with high stereospecificity via an intramolecular hydrogen bond (IHB) directed approach, involving the reaction of methyl ketones (1), N-bromosuccinimide (NBS) (2), isatins (4) and thiosemicarbazide (5) in ethanol at reflux temperature for 45–60 min in one-pot. The reaction proceeds through the construction of C–Br (α-bromination), C–S & C–N (heterocyclization), and CN (condensation) bonds in one pot. The absolute structure of the compound (Z)-3-(2-(4-(4-bromophenyl)thiazol-2-yl)hydrazono)indolin-2-one (6e) has been confirmed by single-crystal XRD analysis. Further, the role of IHB on Z-configuration of the synthesized (Z)-THIs is proved by single-crystal XRD and 1H NMR studies. Wide substrate scope, good functional group tolerance, scalability, improved safety since the method circumvents the use of highly lachrymatric α-bromoketones as starting materials, high product yields (up to 98%), short reaction times, reusable solid Brønsted acid catalyst (HClO4–SiO2), and products that do not require column chromatography purification are all attractive features of this FCDR strategy. Electrochemical properties of THIs (6) are examined by cyclic voltammetry. The HOMO and LUMO energy level of THIs, 6a, 6c, 6d, 6j, 6o-6v, 6y, and 6aa are comparable with the reported ambipolar materials, and the HOMO levels of other THIs, 6b, 6e-6i, 6n, 6w, 6x, 6z and 6 ab-6ae are similar with the most commonly used hole transporting materials (HTMs).

Synthesis of New Methoxy Actived Mono and Bis-indole Compounds

An indole hydrazone has successfully been synthesized employing Schiff base reaction conditions starting from 4,6-dimethoxy-2,3-diphenylindole-7-carbaldehyde with hydrazine hydrate. The reaction of this compound with acetone yielded indole based imine compound. The structure of targeted compound was identified by mass and 1H spectroscopy along with single crystal X-ray diffraction technique. Also, bromination of bis-indole with N-bromo succinimide was produced corresponding bromo bis-indol derivative.

Efficient Construction of Tetracyclic 1,2,4‐Triazoline‐Fused Dibenzo[b,f][1,4]oxazepines through KI/TBHP‐Mediated [3+2] Annulation between DBO‐Imines and N‐Tosylhydrazones

AbstractThe KI/TBHP (tert‐butyl hydroperoxide) promoted [3+2] annulation between dibenzo[b,f][1,4]oxazepine‐imines (DBO‐Imines) and N‐tosylhydrazones under mild conditions has been developed, affording a direct and high atom‐economical preparation for tetracyclic 1,2,4‐triazoline‐fused dibenzo[b,f][1,4]oxazepines (DBOs) in good to excellent yields. This procedure could tolerate a wide range of functional groups and could also be conveniently conducted on a gram‐scale reaction, even in a one‐pot fashion. The produced 1,2,4‐triazoline‐fused DBOs could be easily converted into biologically interesting 1,2,4‐triazolo‐fused DBOs under the action of NBS (N‐bromosuccinimide).

Visible-Light-Induced [4+1] Cyclization-Aromatization of Acylsilanes and α,β-Unsaturated Ketones

Visible-Light-Induced [4+1] Cyclization-Aromatization of Acylsilanes and α,β-Unsaturated Ketones

Catalyst‐Free Site‐Selective Diverse Functionalization of Inherent C–H Bonds in 1‐Aryl‐β‐carbolines, Norharmane and Harmine

AbstractA catalyst‐free, site‐selective diverse functionalization of latent C−H bonds in 1‐aryl‐β‐carbolines and natural norharmane and harmine has been accomplished. This method enables the functionalization of 1‐aryl‐β‐carbolines as C6‐chlorination, C6‐bromination, and C4‐nitration employing cost‐effective, eco‐friendly reagents such as trichloroisocyanuric acid (TCCA), N‐bromosuccinimide (NBS) and tert‐butyl nitrite (TBN), respectively. Pleasingly, these catalyst‐/additive‐free strategies were suitable with a broad range of substrate functionalities of different electronic nature, providing moderate to good yields of functionalized 1‐aryl‐β‐carbolines. The critical/sensitive functionalities such as ‐CF3, ‐NO2, ‐CN, and 1‐(thiophen‐2‐yl)‐β‐carboline were successfully employed, offering corresponding C6‐halogenated or C4‐nitrated products without strain. Furthermore, site‐selective chlorination and bromination of two natural alkaloids such as harmine, norharmane were realized, resulting in corresponding halogenated products, including natural product eudistomin‐N. In addition, we also employed these products in further diversification through ‐NO2 reduction and Suzuki (C−C) coupling of brominated compounds to deliver a C6‐arylated product.

Potential Application of Carbon‐based Electrical Sensor for the Highly Sensitive Diltiazem HCl Quantification in its Pharmaceutical Products and Biological Samples

AbstractDiltiazem (DTZ) hydrochloride, a calcium channel blocker compound, is a very well‐known drug used by many clinicians to treat important diseases playing a role in increased morbidity and mortality among adults worldwide, namely hypertension, cardiac arrhythmia, and ischemic heart disease (angina pectoris). These diseases are a common public health concern, implying that the construction of a specific, accurate, and simple sensor for DTZ determination is needed. Herein, an innovative, portable, and sensitive modified carbon paste electrode (MCPE) was seamlessly developed based on the affordable green compound N‐bromosuccinimide (NBS) as a sensing material and tricresyl phosphate as a solvent mediator for the voltammetric determination of DTZ. The proposed NBS‐MCPE exhibited an excellent electrocatalytic activity towards the oxidation of DTZ molecules in a phosphate buffer solution of pH 5.0 in presence of 20 μM sodium dodecyl sulfate to improve the developed sensor performance. The sensor was found to respond linearly to the DTZ drug over a wide concentration ranging from 1 μM to 300 μM with a low limit of detection. LSV and EIS measurements were also used to scrutinize our sensor, in addition to using scanning electron microscopy and energy dispersive X‐ray analysis techniques for its surface morphology inspection before and after soaking in the drug‐containing solution. The applicability of the proposed sensor for the rapid, sensitive, and selective determination of DTZ in pharmaceutical preparation and human urine samples was assessed and the obtained results were compared with that of the reported HPLC analytical method.

Kinetics Study of the Reaction between Serine and N-Bromosuccinimide in the Presence of Palladium (Pd2+)

The oxidation of serine using N-bromosuccinimide (NBS) has been studied at fix pH value. The reaction presents a first-order reaction with respect to both substrate and oxidant. It is noted that the rate of reaction increases with increasing the palladium ion concentration. The addition of the reaction product (succinimide) affects the oxidation reaction rate. The protonated Br+ or NBrS and NBrS are used to be the reactive species of the N-bromosuccinimide. Furthermore, intermediate compounds are noticed through the reaction. Finally, a mechanism for the oxidation reaction is suggested in this work.

New spectrophotometric method for determination of mebendazole by oxidative coupling reaction

A rapid , simple, accurate and sensitive spectrophotometric method was developed for determination of mebendazole ( MBL ) in pure form and in its pharmaceutical dosages. This method depend on oxidation of MBL with excess amount of N-bromosuccinimide ( NBS ) in acidic medium with standing for complete the reaction , and the oxidized MBL coupled with Rhodamine B to get red product related with MBL amount and measuring the absorbance of surplus dye at 570 nm. A linear calibration curve was obtained over the concentration range 2.5 – 30 μg.ml-1 with correlation coefficient of 0.9992. The molar absorptivity and sandell's sensitivity index values were determined to be 1.476 × 104 L.mol-1.cm-1 and 0.02 μg.cm-2. The limit of detection (LOD) and quantification (LOQ) were calculated to be 0.469 and 1.982 μg.ml-1, respectively . The proposed method has been successfully applied to the determination of MBL in available dosage form, the validity proposed method was confirmed by recovery study via standard addition technique.

Enhanced Reactivity for Aromatic Bromination via Halogen Bonding with Lactic Acid Derivatives.

We report a new method for regioselective aromatic bromination using lactic acid derivatives as halogen bond acceptors with N-bromosuccinimide (NBS). Several structural analogues of lactic acid affect the efficiency of aromatic brominations, presumably via Lewis acid/base halogen-bonding interactions. Rate comparisons of aromatic brominations demonstrate the reactivity enhancement available via catalytic additives capable of halogen bonding. Computational results demonstrate that Lewis basic additives interact with NBS to increase the electropositive character of bromine prior to electrophilic transfer. An optimized procedure using catalytic mandelic acid under aqueous conditions at room temperature was developed to promote aromatic bromination on a variety of arene substrates with complete regioselectivity.

Spectrophotometric determination of cefixime using hydralazine as coupling reagent

A sensitive, accurate, and easy indirect spectrophotometric method was developed for the determination of cefixime in its pure form and in the pharmaceutical preparation (capsules). The method depended on the oxidation of the mixture of the medicinal compound cefixime by the oxidizing agent N-Bromo succinimide, followed by the addition of the reagent hydralazine. A brown complex was obtained and the absorption was measured at 360 nm for the medicinal compound cefixime, its molar absorbance was 2038.6 liters. Mol-1. cm-1. With a recovery rate of 99.33, the method was developed to be simple, inexpensive and fast because it does not include any solvent extraction. The method was successfully applied to the pharmaceutical preparation.

New method for estimation of metronidazol by oxidative coupling reaction using phenothiazine reagent

A Spectrophotometry method was developed to be faster and more sensitive to determine the purity of metronidazole compound. This method is relying on the reaction of oxidation and conjugation with phenothiazine in the acidic medium and with presence of N-bromo succinimide compound as oxidative factor to give a red product at the wavelength 514 nm. This is will be within the range of Beer's law (5-50 ppm), molar absorbance (2.0538 × 103 L.mol-1.cm-1), correlation coefficient (0.998), and Sandellʹs sensitivity (0.0833 µg/cm2). Limits of detection (LOD) (4.6 x 10-3 ppm). This method was successfully applied to pharmaceutical preparations.

Eco-friendly and rapid extraction of gold by in-situ catalytic oxidation with N-bromosuccinimide

Gold is a valued, critical element whose chemical activation or extraction is challenging. Non-cyanide extraction of gold is now the focus, and N-bromosuccinimide(NBS) is attracting attention. Herein, new insights into the possible mechanism are deeply revealed through comprehensive analysis and detection of the reaction by using elementary gold and gold bearing ore. Experiments on gold foil indicate that Au can be activated in NBS solution to perform a satisfactory dissolution. Application of NBS in gold extraction from ore show a high yield of 86.24% under optimal conditions of NBS dosage 0.05 M, liquid-solid ratio 4:1, stirring speed 400 rpm, pH 8, 25 °C and leaching for 20 h, while yields of other coexisting metals are nearly negligible. The process leads to direct, efficient, one-pot conversion of gold, into simple water-soluble salts. Characterizations show that the framework of NBS are not destroyed, only bromine separates from the framework. The oxidation of neutral gold atom to trivalent Au(III) occurs in a mild, clean and room-temperature chemistry, which converts gold to [AuBr4]-, and the framework to succinimide. The active bromine and radical Br (Br•) generated from in-situ autocatalysis of NBS are responsible for this. The systematic results herald a green procedure for preparation of gold derivatives and gold extraction industry.

Tailored sequencing of highly brominated Poly(ether ether ketone) as a means to preserve crystallizability and enhance Tg

In this report, the bromination of poly(ether ether ketone) (PEEK) using the mild reagent N-bromosuccinimide (NBS) is explored to generate controlled random and blocky microstructures. Bromination proceeded quantitatively in both the solution state and semicrystalline gel-state, and degrees of bromination between 25 and 175 mol% were obtained for both random and blocky BrPEEK. Spectroscopic evidence revealed a higher prevalence of unfunctionalized repeat units for blocky BrPEEK than random BrPEEK at similar degrees of functionality. Furthermore, at similar degrees of bromination, blocky BrPEEK exhibited enhanced glass transition temperatures, greater crystallizability, higher melting temperatures, and faster crystallization kinetics than random BrPEEK, suggesting longer segments of unfunctionalized PEEK in blocky BrPEEK. Overall, this work demonstrates that PEEK can be brominated to very high degrees of substitution in the semicrystalline gel-state while preserving crystallizability and effectively blocking up the functionality.

Organocatalytic Enantioselective α-Bromination of Aldehydes with N-Bromosuccinimide.

Despite the wealth of existing organocatalytic, enantioselective transformations, the α-bromination of aldehydes remains a challenging reaction. The four examples reported to date require expensive, inconvenient brominating agents to achieve the desired products in excellent yields and enantioselectivities. The preferred brominating agent, N-bromosuccinimide (NBS), has been repeatedly discarded for these reactions because it results in low yields and relatively poor enantioselectivities. We describe a methodology that uses NBS and performs excellently with low catalyst loadings, short reaction times, and mild temperatures.

High-performance thin-layer chromatography in combination with an acetylcholinesterase-inhibition bioassay with pre-oxidation of organothiophosphates to determine neurotoxic effects in storm, waste, and surface water

Pesticides such as organothiophosphates (OTPs) are neurotoxically active and enter the aquatic environment. Bioassays, using acetylcholinesterase (AChE), a suitable substrate and reactant, can be applied for the photometric detection of AChE-inhibiton (AChE-I) effects. The oxidized forms of OTPs, so-called oxons, have higher inhibition potentials for AChE. Therefore, a higher sensitivity is achieved for application of oxidized samples to the AChE assay. In this study, the oxidation of malathion, parathion, and chlorpyrifos by n-bromosuccinimide (NBS) was investigated in an approach combining high-performance thin-layer chromatography (HPTLC) with an AChE-I assay. Two AChE application approaches, immersion and spraying, were compared regarding sensitivity, precision, and general feasibility of the OTP effect detection. The oxidation by NBS led to an activation of the OTPs and a strong increase in sensitivity similar to the oxons tested. The sensitivity and precision of the two application techniques were similar, although the spray method was slightly more sensitive to the oxidized OTPs. The 10% inhibition concentrations (IC10) for the spray approach were 0.26, 0.75, and 0.35 ng/spot for activated malathion, parathion, and chlorpyrifos, respectively. AChE-I effect recoveries in samples from a stormwater retention basin and receiving stream were between 69 and 92% for malathion, parathion, and chlorpyrifos. The overall workflow, including sample enrichment by solid-phase extraction, HPTLC, oxidation of OTPs, and AChE-I assay, was demonstrated to be suitable for the detection of AChE-I effects in native water samples. An effect of unknown origin was found in a sample from a stormwater retention basin.

Sonochemical Synthesis and In Silico Evaluation of Imidazo[1,2-a]Pyridine Derivatives as Potential Inhibitors of Sirtuins

Encouraged by the reported sirtuin modulating ability of an imidazopyridazine derivative the structurally relevant imidazo[1,2-a]pyridine framework was explored for the design and synthesis of prospective inhibitors of sirtuins. The synthesis of targeted imidazo[1,2-a]pyridine derivatives was carried out via a NBS (N-bromosuccinimide) promoted reaction of 2-aminopyridines with β-keto esters (or 1,3-dione derivatives) in PEG-400 under ultrasound irradiation. This sonochemical method afforded the desired product in good yield when 2-aminopyridines containing electron donating methyl group were employed whereas the corresponding products were obtained in low yields when the electron withdrawing chloro group was present in 2-aminopyridines. The use of 1,3-diones in place of β-keto esters generally afforded the corresponding products in moderate to low yields. The compounds obtained from 1,3-diones were evaluated in silico against SIRT1, 2 and 3 for their potential inhibitory properties against these proteins. The carbonyl group generally played an important role in the interaction of test compounds with the target protein via formation of H-bond(s) with the appropriate residue(s). The docking studies also indicated the selective inhibition of SIRT1 over SIRT2 and 3 by the compound 4a whereas the selective SIRT3 inhibition was specified for compound 3x. Additionally, the in vitro SIRT1 inhibition e.g. 66.7 ± 2.1, 76.8 ± 1.3, 51.9 ± 3.0 and 70.1 ± 1.9% shown by 3x, 4a, 4b and 4c, respectively at 10 µM corroborated the in silico findings concerning this protein.

Indirect Spectrophotometric Determination of Mebendazole Using Methyl Orange Dyein the Presence of the Oxidizing Agent NBS

Aim: To develop a swift , simple, accurate and sensitive spectrophotometric method for determination of mebendazole (MBZL) in pure and pharmaceutical formulations. Methods: The suggested method depend on oxidation of MBZL with known excess amount of N-bromosuccinimide ( NBS ) in acidic medium and after reaction is insured to be complete , the surplus NBS is estimated by de colorization of methyl orange (MO) dye and measuring the absorbance of surplus dye at 508 nm. A linear calibration curve was obtained over the concentration range 2.5– 25 μg.ml-1 with correlation coefficient of 0.9997. The molar absorptivity and sandell's sensitivity index values were determined to be 1.505 × 104 L.mol-1.cm-1 and 0.019607 μg.cm-2. The limit of detection (LOD) and quantification (LOQ) were calculated to be 0.3736 and 2.553 μg.ml-1, respectively. The proposed method has been successfully applied to the determination of MBZL in available dosage form, the validity proposed method was confirmed by recovery study via standard addition technique . Keywords: mebendazole ; N-bromosuccinimide ; Determination ;Spectrophotometry ; methyl orange

Kinetics of catalytic activities of micro amount of Ir(III) in oxidation of D(-) Galactose by N-bromosuccinimide in acidic homogeneous medium

It has been investigated how iridium(III) catalyses the oxidation of D(-)Galactose by N-bromosuccinimide (NBS) in an aqueous perchloric acid solution at 308 K. NBS kinetics is first-order, while galactose kinetics is zero-order. As a function of [Ir(III)], the reactions demonstrate first order at lower [Ir(III)] and zero-order behaviour at higher [Ir(III)]. On the rate of oxidation, inverse fractional-order has been reported in [H+], [Cl-] and [succinimide]. There is no difference in the rate of oxidation with changes in the ionic strength of the medium or with the addition of Hg(OAc)2 (a Br-ion scavenger). Galactonic acid has been identified as the major oxidation product of the process. It is possible to compute the activation parameters by utilizing the rate constants observed at four distinct temperature levels. For the sake of this research, it is hypothesised that HOBr and [IrCl5H2O]2-are both reactive species oxidants (i.e. NBS) as well as catalysts. It is very probable that the reaction mechanism for the oxidation of galactose by NBS is supported by current kinetic data, reaction stoichiometry, and product analysis.