N-bromosuccinimide Research Articles

Application of Relay C−H Oxidation Logic to Polyhydroxylated Oleanane Triterpenoids

Summary Although clinical applications of abundant feedstock triterpenoids such as oleanolic acid are limited because of poor solubility and bioavailability, synthetic access to higher hydroxylated oleanane terpenoids is challenging. We now report the use of relay C−H oxidation logic to mimic the processes carried out in nature by P450 monooxygenase enzymes. To this end, we used the C-23-OH as natural handle for a hydrogen-atom transfer to access C-6, enabling the first syntheses of highly oxidized natural products uncargenin C and protobassic acid as well as uncovering the anti-leukemic activity of a synthetic intermediate.

Rhodium-Catalyzed ortho-Bromination of O-Phenyl Carbamates Accelerated by a Secondary Amide-Pendant Cyclopentadienyl Ligand.

It has been established that a newly developed cyclopentadienyl rhodium(III) [CpA RhIII ] complex, bearing an acidic secondary amide moiety on the Cp ring, is able to catalyze the ortho-bromination of O-phenyl carbamates with N-bromosuccinimide (NBS) at room temperature. The presence of the acidic secondary amide moiety on the CpA ligand accelerates the bromination by the hydrogen bond between the acidic NH group of the CpA ligand and the carbonyl group of NBS.

Ni-Catalyzed Enantioconvergent Coupling of Epoxides with Alkenylboronic Acids: Construction of Oxindoles Bearing Quaternary Carbons

We have developed a nickel- nickel/bisphosphine-catalyzed stereoconvergent cross-coupling reaction of epoxides with alkenylboronic acids. Racemic spiroepoxyoxindoles were converted to chiral homoal...

Triazole‐fused indolo[2,3‐a]carbazoles: synthesis, structures, and properties

AbstractThe synthesis, structure, and photophysical and electrochemical properties of triazole fused indolo[2,3‐a]carbazole derivatives 2‐5 are reported. The key step involved in the synthesis of triazole fused indolo[2,3‐a]carbazole derivatives is the Cadogan ring closing reaction. 2‐Hexyl‐5,6‐dinitro‐2H‐benzo[d][1,2,3]triazoles having 4,7‐diaryl capping were subjected to the Cadogan cyclization reaction to obtain compounds 2‐5. In contrast to thiadiazole‐fused indolo[2,3‐a]carbazole 1, bromination of triazole‐fused indolo[2,3‐a]carbazole 4 afforded only meta‐dibrominated product with respect to the nitrogen of fused pyrrole rings on treatment with both N‐bromosuccinimide (NBS) and elemental bromine. These compounds showed positive solvatochromism in their emission spectra. Incorporation of electron‐donating substituent in the indole moiety resulted in the elevation of the highest occupied molecular orbital (HOMO) level. Density functional theory (DFT) calculations were performed to support the experimental findings.

Spectrophotometric Method for Indirect Determination Of Antihypertensive Drugs in Pharmaceuticals

Abstract A spectrophotometric method is proposed for the determination of antihypertensive drugs namely Propranolol and Methyldopa in their pure forms and in pharmaceutical formulations, based on the oxidation of the drugs with an excess of N-Bromo succinimide and the residual oxidizing agent bleaches the red colored eriochrom black-T (EBT) which is measured at 530 nm at room temperature. Linear calibration graphs were obtained in the concentration range 0.1-10 and 0.1-9 μg ml-1 with molar absorptivity 6.06×104 and 4.60×104 L.mol-1.cm-1 for above drugs respectively. No interference was observed coexistent substance. The proposed method was applied successfully for the determination of the drugs in their pharmaceutical formulations.

ANS Interacts with the Ca2+-ATPase Nucleotide Binding Site.

The binding of 8-anilino-1-naphthalene sulfonate (ANS) to the nucleotide binding domain (N-domain) of the sarcoplasmic reticulum Ca2+-ATPase (SERCA) was studied. Molecular docking predicted two ANS binding modes (BMI and BMII) in the nucleotide binding site. The molecular interaction was confirmed as the fluorescence intensity of ANS was dramatically increased when in the presence of an engineered recombinant N-domain. Molecular dynamics simulation showed BMI (which occupies the ATP binding site) as the mode that is stable in solution. The above was confirmed by the absence of ANS fluorescence in the presence of a fluorescein isothiocyanate (FITC)-labeled N-domain. Further, the labeling of the N-domain with FITC was hindered by the presence of ANS, i.e., ANS was bound to the ATP binding site. Importantly, ANS displayed a higher affinity than ATP. In addition, ANS binding led to quenching the N-domain intrinsic fluorescence displaying a FRET pattern, which suggested the existence of a Trp-ANS FRET couple. Nonetheless, the chemical modification of the sole Trp residue with N-bromosuccinimide (NBS) discarded the existence of FRET and instead indicated structural rearrangements in the nucleotide binding site during ANS binding. Finally, Ca2+-ATPase kinetics in the presence of ANS showed a partial mixed-type inhibition. The Dixon plot showed the ANS-Ca2+-ATPase complex as catalytically active, hence supporting the existence of a functional dimeric Ca2+-ATPase in sarcoplasmic reticulum vesicles. ANS may be used as a molecular platform for the development of more effective inhibitors of Ca2+-ATPase and appears to be a new fluorescent probe for the nucleotide binding site. Graphical Abstract Molecular docking of ANS to the nucleotide binding site of Ca2+-ATPase. ANS fluorescence increase reveals molecular interaction.

Lipophilic indole mediated chemoselective α-monobromination of 1,3-dicarbonyl compounds

A mild and efficient mono-selective bromination of 1,3-dicarbonyl compounds has been developed using lipophilic indole catalysts. Inexpensive and commercially available N-bromosuccinimide (NBS) was used as the brominating reagent. The selectivity was further enhanced when using stoichiometric amount of 3-bromoindole species. Mechanistic studies reveal that the indole catalyst has dual functions in the mono-bromination process.

Regioselective Bromination of the Dextran Nonreducing End Creates a Pathway to Dextran-Based Block Copolymers

Preparation of polysaccharide-based block copolymers with linear architectures is an important goal, opening up clear application potential and requiring significant advances in polysaccharide regio- and chemoselectivity. Herein we report a simple approach to prepare dextran-based block copolymers. Reaction with N-bromosuccinimide (NBS)/triphenyl phosphine (PPh3) regioselectively brominates the sole primary alcohol of linear, unbranched dextran at C-6 of the nonreducing end monosaccharide. The resulting dextran, monofunctionalized with a terminal C-6 bromide, was coupled with various amine terminated polymers to prepare block copolymers, including dextran-b-poly(ethylene glycol), dextran-b-polystyrene, and dextran-b-poly(N-isopropylacrylamide). These renewable-based block copolymers, prepared in two selective, high-yielding steps from native linear dextran, exhibit various interesting properties. Dextran-b-poly(N-isopropylacrylamide) undergoes thermally induced micellization as revealed by dynamic light scattering (DLS), forming micelles upon exceeding 33 °C. We also observed microphase separation in dextran-b-polystyrene by using small-angle X-ray scattering (SAXS). Overall, this methodology provides a new, highly chemo- and regioselective, versatile route to diverse dextran-based block copolymers with useful properties, enabling drug delivery, compatibilization, and other applications.

Chloramine-T/N-Bromosuccinimide/FeCl3/KIO3 Decorated Graphene Oxide Nanosheets and Their Antibacterial Activity.

In this work, we report the synthesis of graphene oxide nanosheets (GO NS) using four different oxidants, namely, chloramine-T (CAT), FeCl3, N-bromosuccinimide (NBS), and KIO3. Fourier transform infrared spectroscopy (FTIR) was used to characterize the functional groups present in the synthesized GO. The microstructure analysis was performed using X-ray diffraction (XRD) and scanning electron microscopy (SEM) to investigate the morphology of GO. High-resolution transmission electron microscopy (HRTEM) studies demonstrated the nanostructure and crystalline phases of GO. The antibacterial activity of the prepared GO NS was investigated against pure cultures of Pseudomonas pneumonia and Staphylococcus aureus. The synthesized GO NS with CAT-GO (C-GO) exhibited very good antibacterial activity towards pathogens.

Kinetics Spectrophotometric determination of Ranitidine based on its Inhibitory effect on the Oxidation Rate of Malachite green by N-bromosuccinide

A simple and sensitive kinetic spectrophotometric method is described for the determination of ranitidine. The method is based on the inhibiting effect of ranitidine on the rate of oxidation of malachite green (MG+ ) with N-bromosuccinimide (NBS) The oxidation reaction was followed spectrophotometrically by measuring the rate of change of the absorbance of malachite green with time at λ=617nm in the presence of different concentrations of ranitidine using the recommended procedure. Ranitidine can be determined from 0.08 to 2.40 g ml-1 with a linear calibration graph and detection limit of 0.026 g ml-1 . The method was successfully applied for the determination of ranitidine in pure ranitidine samples and in ranitidine tablets. The recovery of the analyzed samples were 97-100% with relative standard deviation, sr (%) =1.14 x 10-4 indicating high accuracy and precision of the suggested method. The interference of various cations and anions in the determination of ranitidine was studied

Ultrasound Promoted Synthesis and Antimicrobial Evaluation of Novel Seven and Eight-Membered 1,3-Disubstituted Cyclic Amidinium Salts

Series of 1,3-dibenzyl-1H-4,5,6,7-tetrahydro-1,3-diazepinium and 1,4,5,6,7,8-hexahydro-1,3-diazocinium salts derivatives were efficiently synthesized in excellent yields by dehydrogenation of the corresponding N,N'-dibenzyl aminals employing N-bromosuccinimide (NBS) as dehydrogenating agent under ultrasound irradiation. The present methodology has proven to be simple, efficient and environmentally benign. All novel compounds were identified and characterized by 1H and 13C NMR spectra. The synthesized compounds were screened for their antimicrobial activities.

An Efficient and Green Microwave-Assisted One Pot Synthesis of Imidazothiadiazoles in PEG-400 and Water

Imidazothiadiazoles have attracted great deal of interest because of its several valuable diversified applications in the field of medicinal chemistry. Therefore, there is, requirement to design new environmentally benign protocol for the synthesis of benzo[d]imidazo[2,1-b]thiazoles. Herein, a simple, rapid, green and one-pot cascade process has been developed for synthesis of benzo[d]imidazo [2,1-b]thiazoles from the condensation of aromatic ketones, NBS (N-bromosuccinimide) and 5-(Biphenyl-4-yl)-1,3,4-thiadiazol-2-amine under microwave irradiation at 80–85 °C in PEG (polyethylene glycol)-400 and water as a green reaction medium. The product obtained in good to excellent yield (94-98%) in minimum reaction time.

Metal-Free Synthesis of 4-Chloroisocoumarins by TMSCl-Catalyzed NCS-Induced Chlorinative Annulation of 2-Alkynylaryloate Esters.

4-Chloroisocoumarins can be conveniently prepared from 2-alkynylaryloate esters via the activation of alkynes by electrophilic chlorine, generated in situ from N-chlorosuccinimide (NCS) in the presence of 10 mol % trimethylsilyl chloride (TMSCl), which leads to 6-endo-dig-selective chlorinative annulation to give the desired products in moderate to quantitative yields. The procedure employs readily available reagents and can be conveniently carried out on a wide scope of substrates under mild conditions (0 °C to rt). Furthermore, the reaction is scalable for gram-scale preparation of 4-chloroisocoumarins. Additionally, 4-bromo- and 4-iodoisocoumarins can be prepared in moderate to good yields by replacing NCS with N-bromosuccinimide (NBS) and N-iodosuccinimide (NIS), respectively.

Comparison of Vitamin C Content of Commercially Available Fresh Fruits

Aims: The aim of the current paper is to identify the ascorbic acid level in ten commercially available fruits in order to expand the existing database about fruits rich in Vitamin C and to promote their daily consumption.
 Study Design: Research was conducted experimentally.
 Place and Duration of Study: University of food technologies, Plovdiv, Bulgaria, October 2019.
 Methodology: Ascorbic acid levels were determined with the use of two oxidation-reduction titration methods – Dichlorophenoliodophenol (DCPIP) and N-Bromosuccinimide (NBS).
 Results: All studies samples possessed different amounts of ascorbic acid. Both DCPIP and NBS assay resulted in determining strawberries as the fruit with the highest ascorbic acid levels – 55.1 ± 1.6 mg/100 g and 59.8 ± 2.2 mg/100 g respectively. Lowest values were obtained for fig. All results are commensurable to those obtained in other studies. Ascorbic acid levels were as follows: strawberries > grapefruit > pear > green apple > blueberries > quince > banana > plum > white grapes > fig.
 Conclusion: In this study, ten commercially available fruits were studied for their ascorbic acid levels. Comparison between two titration methods showed moderate differences in the results confirming that the NBS method is more sensitive. All reported data confirms that differences occur, but fruits can be considered sources of vitamin C.

Microwave‐Assisted Metal‐Free Decarboxylative Iodination/Bromination of Isoxazole‐4‐carboxylic Acids

AbstractA microwave‐assisted metal‐free route to substituted 4‐haloisoxazoles via decarboxylative halogenation of substituted isoxazole‐4‐carboxylic acids using N‐iodosuccinimide (NIS) and N‐bromosuccinimide (NBS) in the presence of K3PO4 is described. It was discovered that the substitutions present at the 3‐position of differently 3,5‐disubstituted isoxazoles influenced the outcome of the protocol. The methodology is compatible for performing decarboxylative halogenation followed by decarboxylative Suzuki‐Miyaura and Sonogashira couplings as one‐pot process.

SYNTHESIS AND ANTIOXIDANT EVALUATION OF 3-BROMO-FLAVONE

Objective: The objective of the study was to obtain a flavone derivative compound through N-bromosuccinimide (NBS) reducing the reaction. Theantioxidant activity of the synthetic compound was then assayed by the 2,2-diphenyl-1-picrylhydrazyl method.Methods: Chalcone (3 mmol) as intermediate precursor was suspended with dimethyl sulfoxide and reacted with NBS (3 mmol), stirred at roomtemperature for 25 min and diluted in cold water. The synthesis of flavone derivatives resulted in yellow crystalline powder, freely soluble in methanoland ethanol, renamed 60% with a melting point of 87.7°C. Detection by thin-layer chromatography using hexane:chloroform (2:1) showed single spotwith Rf = 0.38 which is different from the Rf value of the starting compound (chalcone, 0.66 and 0.78).Results: The results of the characterization of the synthesized compound using ultraviolet-visible and Fourier transform-infared showed the groupcharacteristic containing C=C (1604.77 and 1639.49 cm-1), C=O (1681.93 cm-1), C-O-C (1242.16 cm-1), Ar-H (3032.1 and 3062.96 cm-1), and C-Br(663.51 cm-1) at maximum absorption of wavelength 253 nm.Conclusion: The synthesis of flavone using NBS resulted in 3-bromo-flavone with a weak antioxidant activity.

A Crystallographic Charge Density Study of the Partial Covalent Nature of Strong N⋅⋅⋅Br Halogen Bonds.

The covalent nature of strong N-Br⋅⋅⋅N halogen bonds in a cocrystal (2) of N-bromosuccinimide (NBS) with 3,5-dimethylpyridine (lut) was determined from X-ray charge density studies and compared to a weak N-Br⋅⋅⋅O halogen bond in pure crystalline NBS (1) and a covalent bond in bis(3-methylpyridine)bromonium cation (in its perchlorate salt (3). In 2, the donor N-Br bond is elongated by 0.0954 Å, while the Br⋅⋅⋅acceptor distance of 2.3194(4) is 1.08 Å shorter than the sum of the van der Waals radii. A maximum electron density of 0.38 e Å-3 along the Br⋅⋅⋅N halogen bond indicates a considerable covalent contribution to the total interaction. This value is intermediate to 0.067 e Å-3 for the Br⋅⋅⋅O contact in 1, and approximately 0.7 e Å-3 in both N-Br bonds of the bromonium cation in 3. A calculation of the natural bond order charges of the contact atoms, and the σ*(N1-Br) population of NBS as a function of distance between NBS and lut, have shown that charge transfer becomes significant at a Br⋅⋅⋅N distance below about 3 Å.

A Crystallographic Charge Density Study of the Partial Covalent Nature of Strong N⋅⋅⋅Br Halogen Bonds

AbstractThe covalent nature of strong N−Br⋅⋅⋅N halogen bonds in a cocrystal (2) of N‐bromosuccinimide (NBS) with 3,5‐dimethylpyridine (lut) was determined from X‐ray charge density studies and compared to a weak N−Br⋅⋅⋅O halogen bond in pure crystalline NBS (1) and a covalent bond in bis(3‐methylpyridine)bromonium cation (in its perchlorate salt (3). In 2, the donor N−Br bond is elongated by 0.0954 Å, while the Br⋅⋅⋅acceptor distance of 2.3194(4) is 1.08 Å shorter than the sum of the van der Waals radii. A maximum electron density of 0.38 e Å−3 along the Br⋅⋅⋅N halogen bond indicates a considerable covalent contribution to the total interaction. This value is intermediate to 0.067 e Å−3 for the Br⋅⋅⋅O contact in 1, and approximately 0.7 e Å−3 in both N−Br bonds of the bromonium cation in 3. A calculation of the natural bond order charges of the contact atoms, and the σ*(N1−Br) population of NBS as a function of distance between NBS and lut, have shown that charge transfer becomes significant at a Br⋅⋅⋅N distance below about 3 Å.

Optimization and Validation of the Spectrophotometric Methods for the Assay of Dexmedetomidine Hydrochloride in Pure and Dosage Forms

Four simple, precise, low-cost, sensitive, and diversely applicable UV-Vis spectrophotometric methods have been developed for the assay of dexmedetomidine hydrochloride in pure and pharmaceutical dosage forms. The methods are based on the oxidation of the drug by N-bromosuccinimide (NBS) (excess) at room temperature and estimating the amount of unconsumed NBS by amaranth dye at λmax = 530 nm (method A), safranin dye at λmax = 530 nm (method B), aniline blue at λmax = 610 nm (method C), or rhodamine B at λmax = 560 nm (method D). Regression analysis of Beer–Lambert's plots proves excellent correlation in the concentration ranges 2–9, 4–11, 2–10, and 1.2–3.5 μg/mL for methods A, B, C, and D, respectively. The apparent molar absorptivity, Sandell’s sensitivity, and detection and quantification limits are calculated. The proposed methods can be applied to drug formulation and recommended for routine analysis in quality control laboratories. Statistical comparison of the results with the reference method shows excellent agreement.

Kinetics and mechanism of the oxidative degradation of sofosbuvir by N-bromosuccinimide in aqueous medium

The kinetics of the electron transfer in sofosbuvir (Sofo) using N-bromosuccinimide (NBS) in aqueous medium has been studied spectrophotometrically over the (10–30) °C range, (0.1–0.5) mol dm−3 ionic strength, pH = 6.0–8.0 range over a range of NBS and Sofo concentrations. The rate of reaction was first order dependence on both [NBS] and [Sofo] and decreased with increasing [H+] over the range studied suggesting that the deprotonated form of sofosbuvir is more reactive than its conjugate acid. The hydrogen atom attached to the nitrogen atom of pyrimidine dione ring has a highly acidic character due to withdrawing effect of the adjacent two carbonyl groups and so the sofosbuvir acted as an acid. The rate decreased with increasing the ionic strength of the reaction mixture and supported that the reaction took place between two ions of different charges.