4-nitrobenzyl Bromide Research Articles

Design, Synthesis, and Anti-Prostate Cancer Potential of 2-(4-Nitrobenzyl) Malonates In Vitro and DAL Acute Oral Toxicity Assessment In Vivo.

New 4-nitrobenzyl derivatives were designed and synthesised by nucleophilic substitution reactions of 4-nitrobenzyl bromide with malonic acid and its derivatives. The synthesised molecules were characterised using mass analysis and spectroscopic techniques and tested for their antioxidant properties using various methods, such as nitric oxide, DPPH, and hydrogen peroxide radical scavenging methods. The anti-inflammatory activities of the molecules were assessed using RBC membrane stabilisation and albumin denaturation methods. We evaluated the compounds' potential anti-prostate cancer activity using the DU145 cell line. The MTT assay determined the cell viability, indicating good anti-proliferative activity. The molecule 3 c exhibited the highest potency, with a CTC50 of 11.83 μg/mL. Molecular dynamics simulations were performed to study the stability of the ligand within the protein after docking and the resulting protein-ligand complex. The in vivo analysis of molecule 3 c in the DAL xenograft model demonstrated promising results. The increase in life span, reduction in tumor volume, and comparable effects to standard drugs are encouraging features that suggest that molecule 3 c may possess significant potential as an anti-cancer agent. The research also implies that these molecules might be potential lead compounds for developing new prostate cancer drugs.

Synthesis and antioxidant properties of novel hybrid molecules containing gallic acid and thiazolidinone moieties

Thiazolidinones, are characterized by a thiazolidine ring structure, have highly biological applications. So, novel hybrid thiazolidinone moieties containing gallic acid were synthesized via cyclo-condensation process or standard Knoevenagel reactions. Hydrazineyl-thiazol-4(5H)-one 2 derivative was synthesized to condensed with benzaldehydes to afford benzylidene thiazolidinone derivatives 3a-c. Also, the product 2 reacted with benzyl bromide or nitro benzyl bromide to give their corresponding methylene active derivatives 4a,b which were readily reacted with aromatic aldehydes to produce 5-arylidene derivatives 5a-f via Knoevenagel reactions. The new thiazolidine derivatives were elucidated according to their spectroscopic and elemental analyses. Two thiazolidinone derivatives 4a,b were elucidated via X-ray analysis. Also, antioxidant activity of the new products were run by DPPH assay and in comparison with reference antioxidants (ascorbic acid and BHT). The results revealed that eight compounds was higher than BHT and was increasing in the following order 4a < 5f < 5a< 3c < 5b < 5d < 3a< 5c. The antioxidant activity of ascorbic acid was higher than all compounds in which compound 5c was very close in its activity with the ascorbic acid.

Carbon black intercalation compound as catalyst for unprecedent phase-transfer-catalyzed nucleophilic substitution (SN2) in water

Carbon black intercalation compound was used for the first time as a heterogeneous phase-transfer-catalyst for SN2 type reaction of NaSCN with 4-nitrobenzyl bromide. The reaction proceeds in the presence of 5 mol% of catalyst with high efficiency in a liquid-liquid biphasic system (CHCl3/H2O), providing 98% conversion after only 4 h. Furthermore, an unprecedent efficient nucleophilic substitution was reported in water solution in the presence of the new catalyst, providing 95% yield in 8 h. The reaction is green, and the heterogeneous catalyst can be recovered and recycled without losing efficiency.

Cooperative NHC and nickel-catalyzed asymmetric reductive coupling of nitrobenzyl bromides and cyclic ketiminesviaSET process

A synergistic NHC/Ni catalyzed asymmetric reductive coupling of nitrobenzyl bromides with cyclic ketiminesviaSET process was realized.

In Silico Studies and Design of Scrupulous Novel Sensor for Nitro Aromatics Compounds and Metal Ions Detection.

A Novel calix[4]pyrrole system bearing carboxylic acid functionality [ABuCP] has been synthesized and its interaction towards various nitroaromatics compounds [NACs] were investigated. ABuCP showed significant color change with 1,3-dinitro benzene (1,3-DNB) in comparison to the solution of other nitroaromatic compounds such as 2,3-dinitro toluene (2,3-DNT), 2,4-dinitro toluene (2,4-DNT), 2,6-dinitro toluene (2,6-DNT), 4-NBB (4-nitrobenzyl bromide) and 4-nitro toluene (4-NT). The ABuCP-1,3-DNB complex produces a red shift in absorption spectra based on charge transfer mediated recognition. Additionally, the density functional theory calculation confirmed the possible mechanism for the binding of 1,3-DNB as a guest is well supported by the calculation of other parameters such as hardness, stabilization energy, softness, electrophilicity index and chemical potential. The TDDFT calculation facilitates the understanding of the proper binding mechanism in reference to experimental results. Additionally we have also developed its derivative which acts as a new fluorescent sensor which can selectively recognize Sr(II) ions. In this view its aminoanthraquinone derivative of calix[4]pyrrole i.e. ABuCPTAA is synthesized which also results in generation of high fluorescence capability sensor.

Synthesis of a Novel Series of Cu(I) Complexes Bearing Alkylated 1,3,5-Triaza-7-phosphaadamantane as Homogeneous and Carbon-Supported Catalysts for the Synthesis of 1- and 2-Substituted-1,2,3-triazoles.

The N-alkylation of 1,3,5-triaza-7-phosphaadamantane (PTA) with ortho-, meta- and para-substituted nitrobenzyl bromide under mild conditions afforded three hydrophilic PTA ammonium salts, which were used to obtain a new set of seven water-soluble copper(I) complexes. The new compounds were fully characterized and their catalytic activity was investigated for the low power microwave assisted one-pot azide–alkyne cycloaddition reaction in homogeneous aqueous medium to obtain disubstituted 1,2,3-triazoles. The most active catalysts were immobilized on activated carbon (AC), multi-walled carbon nanotubes (CNT), as well as surface functionalized AC and CNT, with the most efficient support being the CNT treated with nitric acid and NaOH. In the presence of the immobilized catalyst, several 1,4-disubstituted-1,2,3-triazoles were obtained from the reaction of terminal alkynes, organic halides and sodium azide in moderate yields up to 80%. Furthermore, the catalyzed reaction of terminal alkynes, formaldehyde and sodium azide afforded 2-hydroxymethyl-2H-1,2,3-triazoles in high yields up to 99%. The immobilized catalyst can be recovered and recycled through simple workup steps and reused up to five consecutive cycles without a marked loss in activity. The described catalytic systems proceed with a broad substrate scope, under microwave irradiation in aqueous medium and according to “click rules”.

The electrochemical behavior of 4-nitrobenzyl bromide and its catalytic activity for reduction of CO2 in the acetonitrile solvent at the Cu/Pd/rGO/GCE surface

In this study, 4-nitrobenzyl bromide was used as a catalyst for reduction of CO2 and as an initial substrate for electrosynthesis of 4-nitrophenylacetic acid. Cu nanoparticles/Pd nanoparticles/reduced graphene oxide nanocomposite modified glassy carbon electrode (Cu/Pd/rGO/GCE) was used to promote electroactivation of CO2. rGO film was fabricated via electrochemical reduction of dispersed GO nanosheets on the GCE surface. Cyclic voltammetry procedure was applied in two steps to deposit Pd and Cu nanoparticles on the rGO/GCE surface. The morphology and structure of the nanocomposites were characterized using FESEM, EDS, AFM and XRD analysis. FTIR, 1H and 13C NMR spectral characteristics were used to identify the final products of the catalytic process. The electrocarboxylation of 4-nitrobenzyl bromide occurs at a potential which is less negative than those reported for other aryl halides. The results indicate that 4-nitrobenzyl bromide, as a catalyst, plays a dual role in the electrosynthesis of 4-nitrophenylacetate. The dual role includes the electrocatalytic reduction of CO2 and reaction of produced CO2•− with 4-nitrobenzyl bromide radical anion. Finally, an EC’C mechanism is proposed for the electrosynthesis of 4-nitrophenylacetate.

Stereochemistry of oxidative addition reactions of cycloneophyl complexes of Platinum(II): A methylene insertion reaction from dichloromethane

Unusual features are observed in studies of oxidative addition to cycloneophylplatinum(II) complexes [Pt(CH2CMe2C6H4)(NN)], 2, NN = 3,4,7,8-tetramethyl-1,10-phenanthroline (phen*) or 3, NN = 4,4′-di-t-butyl-2,2′-bipyridine (bubipy). The oxidative addition of 4-nitrobenzyl bromide to 2 or of HgCl2 to 3 occurs with cis stereochemistry to give [PtBr(CH2-4-C6H4NO2)(CH2CMe2C6H4)(phen*)] or [PtCl(HgCl)(CH2CMe2C6H4)(bubipy)], whereas similar reactions with dimethylplatinum(II) complexes occur with trans stereochemistry. The reaction of 2 with CH2Cl2 occurs, with formal insertion of methylene into the arylplatinum bond, to give [PtCl2(CH2CMe2C6H4CH2)(phen*)], the first time such a reaction has been observed with the reagent CH2Cl2. Hydrogen peroxide reacts with 2 to give oxidative addition with trans stereochemistry to give [Pt(OH)2(CH2CMe2C6H4)(phen*)] and reaction with chlorinated solvent then gives [PtCl(OH)(CH2CMe2C6H4)(phen*)]. Depending on the reaction conditions, the peroxyacid m-ClC6H4CO3H reacts with 2 to give [Pt(OH2)2(CH2CMe2C6H4)(phen*)](m-ClC6H4CO2)2, [{Pt(OH2)2(CH2CMe2C6H4)(phen*)}.{Pt(OH)(OH2)(CH2CMe2C6H4)(phen*)}](m-ClC6H4CO2)3, or [PtCl{OOC(=O)C6H4Cl-m}(CH2CMe2C6H4)(phen*)]. Computational studies indicate that the stereochemistry of oxidative addition may be determined by kinetic or thermodynamic factors in different cases, and that the unique CH2 insertion reaction with CH2Cl2 occurs by a radical mechanism. X-ray structure determinations are reported for eight of the platinum(IV) complexes.

One-Pot Reaction between N-Tosylhydrazones and 2-Nitrobenzyl Bromide: Route to NH-Free C2-Arylindoles.

A one-pot Barluenga coupling between N-tosylhydrazones and nitro-benzyl bromide, followed by deoxygenation of ortho-nitrostyrenes, and subsequent cyclization has been developed, providing a new way to synthesize various C2-arylindoles. This method exhibits a good substrate scope and functional group tolerance, and it allows an access to NH-free indoles, which can present a potential utility in medicinal chemistry applications.

Synthesis, antioxidant and antibacterial activity of azo dye-stilbene hybrid compounds

PurposeThe purpose of this paper is synthesis and evaluation of antioxidant and antibacterial activities of a series of new azo dyes derived from 4-aminostilbene.Design/methodology/approachFirst, the starting material 4-aminostilbene was prepared via two successive Wittig and reduction reactions from 4-nitrobenzyl bromide. The obtained 4-aminostilbene was then reacted with some phenols under the normal azo coupling reaction conditions to give five new azo products. Antioxidant activity of the azo compounds was determined by radical scavenging assay using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Also, the antimicrobial activity of the compounds against one gram-positive and eight gram-negative strains was evaluated based on the inhibition zone using disc diffusion assay.FindingsThe structures of the azo dyes were identified and characterized by fourier-transform Infrared, 1H nuclear magnetic resonance (NMR) and ultraviolet-visible (UV-V) is spectroscopic methods. All the compounds showed higher antioxidant activity than ascorbic acid (Asc) and butylated hydroxytoluene (BHT) as positive controls. Moreover, the compounds showed lower antibacterial activity than the standard antibiotic vancomycin.Research limitations/implicationsExcellent antioxidant activity, along with antibacterial activity against Streptococcus pneumoniae and Pseudomonas aeruginosa, was observed for the two synthesized azo dyes.Originality/valueFive novel azo dyes based on 4-aminostilbene were synthesized. The dyes have a highly p-extended conjugated structure comprising the phenolic and stilbenic segments, and they indicated good antioxidant activity, so that the two dyes (2c and 2d) even showed much more scavenging activity compared to BHT which is used as an antioxidant agent in food industries. These compounds with highest antioxidant activity also inhibited the growth of S. pneumoniae and P. aeruginosa.

Derivatives of 1-benzyl-4-(4-triphenylvinylphenyl) pyridinium bromide: Synthesis, characterization, mechanofluorochromism/aggregation-induced emission (AIE) character and theoretical simulations

4-(4-triphenylvinyl phenyl) pyridine (TPEPy) was used, along with the benzile bromide derivatives, to prepare 1-benzyl-4-(4-triphenylvinyl phenyl) pyridinium bromide (1) and its derivatives by replacing the benzyl bromide with 4-cyanobenzyl bromide for 2, 4-nitrobenzyl bromide for 3 and 4-trifluoromethyl benzyl bromide for 4, respectively. The maxima of the photoluminescent (PL) spectra of the freshly prepared powder samples of 1 ~ 4 are in the range of 510nm ~ 530nm with the absolute luminescence quantum yields (ALQY) of 88.10% for 1, 4.69% for 2, 1.70% for 3 and 36.30% for 4, respectively, which would redshift to the range of 554nm ~ 571nm with ALQYs of 54.70% for 1, 41.00% for 2, 14.70% for 3 and 43.40% for 4, respectively, after they are ground. At the same time, 1 ~ 4 have no obvious PL bands in dichlormethane solution (10-5mol/L) until ≥ 80% n-hexane was added. Finally, the ground-state geometries and the UV-Vis absorption spectra of 1 ~ 4 were simulated at B3LYP/6-31G(d,p) level to theoretically explain their photophysical behaviors.

Total synthesis and high performance liquid chromatography analysis of phenylethanolamine A

A simple, effective and reliable synthetic method was developed to construct beta-agonist phenylethanolamine A(PEAA) in good yield with 4-nitrobenzyl bromide as the starting material, which underwent SN2 reaction with ethyl acetoacetate, followed by hydrolysis with concentrated HCl and amination by Leukart reaction to furnish 4-(4-nitrophenyl)butan-2-amine(A). A one-pot reaction was studied to construct PEAA skeleton and reduced carbonyl with KBH4, the conditions were optimized, including reaction temperature, reaction time, solvent and the molar ratio of 2-bromo-1-(4-methoxyphenyl)ethanone(B) to A. Meanwhile, a reliable and practical high performance liquid chromography(HPLC) method with UV detector was developed after screening wavelength, chromatographic column and optimization of mobile phase. The optimal conditions of detecting PEAA were water(0.1% formic acid and 0.1% triethylamine)-methanol(volume ratio 44:56) at 278 nm with plus-C18 column. The above synthetic method would be used to synthesize standard reference materials and advance extensive application of analytical method. In order to ensure food safety and safeguard human health, the analytical method might be used as a standard method in detection and supervision of PEAA.

Carbene-Catalyzed Reductive Coupling of Nitrobenzyl Bromide and Nitroalkene via the Single-Electron-Transfer (SET) Process and Formal 1,4-Addition.

A carbene-catalyzed reductive 1,4-addition of nitrobenzyl bromides to nitroalkenes is disclosed. The reaction proceeds via a carbene-enabled single-electron-transfer process that generates radicals as key intermediates. The present study expands the potentials of carbene catalysis and offers unusual transformations for common substrates in organic synthesis.

Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process.

Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions.

Synthesis of ortho-arylated/benzylated arylacetamide derivatives: Pd(OAc)2-catalyzed bidentate ligand-aided arylation and benzylation of the γ-C[sbnd]H bond of arylacetamides

In this paper, we report the Pd(OAc)2/AgOAc, bidentate ligand-directed CH functionalization of the sp2 γ-CH bond of arylacetamides. While, the bidentate ligand-directed site selective functionalization of the β-CH bond of aromatic carboxylic acid derivatives is well known, we herein, report our attempts on the Pd(II)-catalyzed, bidentate ligand-directed arylation, benzylation, alkylation, acetoxylation and hydroxylation of the sp2 γ-CH bond of the arylacetamide systems. The arylation and benzylation of arylacetamides were successful; however, the alkylation and acetoxylation/hydroxylation of arylacetamides were not successful. Various ligands were screened to substantiate the need for the bidentate ligand in the arylation/benzylation of arylacetamides, and 8-aminoquinoline was found to be the best bidentate ligand. Several substituted aryl-/heteroaryl iodides, 4-nitrobenzyl bromide and arylacetamide substrates were used to examine their reactivity pattern and accomplish the substrate scope/generality. In general, the bidentate ligand 8-aminoquinoline-directed arylation of arylacetamides gave the corresponding ortho-diarylated arylacetamides and benzylation of arylacetamides gave the corresponding ortho-mono benzylated arylacetamides as the predominant compounds. Overall, this method has led to the synthesis of new ortho-substituted arylacetamides in good to high yields.

Identification and functional characterization of an epsilon glutathione S-transferase from the beet armyworm (Spodoptera exigua)

In the present study, an epsilon glutathione S-transferase from the beet armyworm Spodoptera exigua (SeGSTe) was cloned and characterized. The SeGSTe gene consists of 746bp full-length cDNA with a 669bp open reading frame encoding a predicted protein of 223 amino acid residues weighing 24.517kDa and an isoelectric point of 6.44. Furthermore, sequence analysis of SeGSTe showed 90% sequence identity to Spodoptera litura GSTe2 and 47–36% to other insect GSTs. Phylogenetic relationship analysis further revealed that SeGSTe is a novel member of the Epsilon-class of GSTs. During S. exigua development, SeGSTe is expressed in the midgut of the prepupa stage but not in the epidermis and fat body. Recombinant SeGSTe (25kDa) purified from baculovirus-infected insect cells was able to protect super-coiled DNA from oxidative damage. It was also able to catalyze the conjugation of both 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene (DCNB), but not 4-nitrobenzyl chloride (4-NBC) and 4-nitrophenethyl bromide (4-NPB), to glutathione (GSH). Additionally, recombinant SeGSTe exhibited an optimal pH of 6.0 and an optimal temperature of 40°C. The enzyme activity of recombinant SeGSTe was sensitive to heavy metals Cu2+ and Cd2+ and was significantly inhibited by various kinds of pesticides including insecticide, herbicide, and fungicide. Taken together, these findings suggest that the SeGSTe may be involved in the detoxification of pesticides and protecting S. exigua against oxidative stress, which provides a molecular basis for understanding the mechanisms of insecticide resistance in S. exigua.

Stability-Indicating HPLC-UV for the Determination of 4-bromomethyl-3-nitrobenzoic acid, a Bioactive Nitrocompound

The nitroaromatic compound 4-bromomethyl-3-nitrobenzoic acid (ANB) is a promising antitumoral agent whose activity has recently been investigated. Forced degradation studies were conducted on ANB with a high-performance liquid chromatography-ultraviolet assay to establish its stability and selectivity. ANB was subjected to degradation studies under hydrolytic (acid and alkaline), oxidative and light exposition conditions. The compound showed greater lability only in acid and alkaline conditions by forming a major degradation product. The chromatographic separation of ANB and its degradation product was achieved on an octadecylsilane column using a mobile phase of methanol-water (80:20, v/v), pH 4.0 adjusted with formic acid, flow rate of 0.7 mL/min, ultraviolet diode array detection at λ 271 nm, injection volume of 20 µL and temperature of 30°C. The method was validated according to International Conference on Harmonization guidelines with respect to precision (average relative standard deviation 0.67%), accuracy (average 99.97%), linearity (y = 118730x + 12912; coefficient of determination > 0.999), specificity and robustness (p > 0.05). The degradation product formed as a result from the hydrolysis of nitrobenzyl bromide, corresponded to its benzyl alcohol, 4-hydroxymethyl-3-nitrobenzoic acid (ANOH) and was characterized by co-elution with a synthetic ANOH working standard.

Regio- and Diastereoselective Synthesis of trans-2,3-Dihydrofuran Derivatives in an Aqueous Medium

A wide variety of fused<i> trans</i>-2,3-dihydrofuran derivatives were synthesized through a one-pot three-component reaction of an aromatic aldehyde, a cyclic β-diketo compound, and an <i>in situ</i>-generated pyridinium ylide in refluxing. The pyridinium ylide was formed from either 2-bromo-1-phenylethanone or 4-nitrobenzyl bromide and pyridine in the presence of 10 mol% of sodium hydroxide. Pyridine plays crucial role in forming the pyridinium salt, which, in turn, forms a nitrogen ylide in the presence of sodium hydroxide. The ylide assists a Michael-initiated ring-closure reaction, but is not itself incorporated in the final product. The protocol is environmentally acceptable because no organic solvent is involved at any stage. Furthermore, the method is highly diastereoselective, gives good yields, and does not involve extensive workup procedures or chromatographic separations, as the desired products can be isolated by filtration and drying.

Synthesis and oxidative cyclization of 3-amino-2-arylazo-5-tert-cycloalkylaminothiophenes

A series of 3-amino-4-arylazo-4,5-dihydrothiophenes has been synthesized by the reaction of arylhydrazonocyanothioacetamides (containing a tert-cycloalkylamino group) with α-halo ketones, 2-chloroacetonitrile, or 4-nitrobenzyl bromide. Their oxidation in the presence of metal acetates was investigated. It was shown that heating in pyridine with Cu(OAc)2 leads to the formation of thieno- [3,4-d]-1,2,3-triazoliumolates.

A General Strategy for the Synthesis of Cyclic N-Aryl Hydroxamic Acids via Partial Nitro Group Reduction

We describe a generalized approach to stereocontrolled synthesis of substituted cyclic hydroxamic acids (3-amino-1-hydroxy-3,4-dihydroquinolinones) by selective reduction of substituted 2-nitrophenylalanine substrates. Compounds in this series have antibacterial properties and have also recently been reported as KAT II inhibitors. The key nitrophenyl alanine intermediates are prepared enantioselectively in excellent yield by phase transfer catalyzed alkylation of the corresponding nitrobenzyl bromides. The scope and limitations of the reductive cyclization transformation have been explored with attention to the effects of substitution pattern and electronics on reaction efficiency and byproduct formation. In addition, a novel activated trifluoroethyl ester cyclization strategy has been developed as an alternate approach to the most sterically demanding systems in this series.