Benzyl Bromide Research Articles

Nickel-Catalyzed Direct Fluorosulfonylation of Vinyl Bromides and Benzyl Bromides for Sulfonyl Fluorides.

An efficient nickel-catalyzed direct fluorosulfonylation of vinyl bromides and benzyl bromides under mild reaction conditions has been developed for sulfonyl fluorides utilizing Na2S2O4 and NFSI as the sulfur dioxide and fluorine sources, respectively. This reaction system tolerates organic bromide compounds, such as β-styryl bromides, alkyl vinyl bromides, and benzyl bromides, to achieve corresponding sulfonyl fluorides in moderate to good yields, with convenient operation, mild conditions, broad substrate scope, good functional group compatibility, and excellent retention of configuration to vinyl bromides.

Chalcogen Bond-Driven Alkylations: Selenoxide-Pillar[5]arene As A Recyclable Catalyst For Displacement Reactions In Water.

A novel strategy to catalyze alkylation reactions through chalcogen bond interaction using a supramolecular structure is presented herein. Utilizing just 1.0 mol% of selenoxide-pillar[5]arene (P[5]SeO) as the catalyst we achieved efficient catalysis in the cyanation of benzyl bromide in water. Our approach demonstrated high efficiency and effectiveness, with the results supported by designed control experiments and theoretical models, highlighting the catalytic effect of the pillar[5]arene through noncovalent interactions. Quantum-chemical calculations (ωB97X-D/def2-TZVP@SMD) pointed out that the catalyzed cyanation reaction followed an SN2-like mechanism, with energy barriers (ΔH‡) ranging from 16.7 to 18.2 kcal mol-1, exhibiting dissociative character depending on the para-substituent. 1H NMR analysis revealed that P[5]SeO acted as a catalyst through inclusion complex formation, facilitating the transfer of the electrophilic substrate to the aqueous solution for nucleophilic displacement. Our reaction protocol proved applicable to various substrates, including aromatic and alpha-carbonyl derivatives. The use of sodium azide as the nucleophile was also feasible. Importantly, our method allowed scalability, and the catalyst P[5]SeO could be recovered and reused effectively for multiple reaction cycles, showcasing sustainability.

Cyclometalated C^C* Platinum(IV) NHC Complexes.

We present a previously unknown series of cyclometalated platinum(IV) NHC complexes, obtained by oxidative addition of iodine, iodomethane, and different benzyl bromides to platinum(II) complexes with cyclometalated C^C* dibenzofuran, dibenzothiophene, and phenylimidazole ligands together with an acetylacetonate ligand. All compounds were characterized by standard techniques (1H, 13C, and 195Pt NMR and elemental analysis), and for three complexes, solid-state structures could be obtained. DFT calculations (B3LYP(d3)/def2-TZVPP including dispersion interactions in dichloromethane and acetone) were performed to investigate the mechanism of the oxidation and explain the exclusive formation of the observed trans products.

Copper-catalyzed three-component reaction to construct thietane ring using elemental sulfur

Thietanes are vital aliphatic four-membered rings associated with various pharmaceuticals, building blocks and synthons of intermediates used in the total synthesis of natural products and biomolecules. Also, 4-thiazolidinone is a core pharmacophore of many drug molecules. Based on their various applications in medicinal chemistry and organic synthesis, an effort has been made to achieve a thietane ring on 4-thiazolidinone nucleus via quasi-benzylic acid-type intramolecular rearrangement using elemental sulfur, benzyl bromide and Cu(I). The designed methodology is environmentally benign, cheap, and easily accessible, with a broad range of substrate scopes and carried out by the employment of earth-abundant metal catalysts like copper.

Voltammetric Investigations of Low-Coordinate Manganese As an Electrocatalyst for Organic Coupling and Functionalization

Earth-abundant, first row, low coordinate transition metal complexes are considered promising candidates for the electrocatalysis of many organic reactions. The use of transition metal catalysts is no stranger to the field of synthetic organic chemistry; however, many of the existing catalysts require the use of rare and expensive metals such as platinum, palladium, ruthenium, and iridium. In this study, we seek to identify and understand the mechanism by which an Mn(I) complex may act as an electrocatalyst for simple organic coupling and C-H functionalization reactions, beginning with the radicalization of benzyl bromide and benzyl chloride as representative organic halide substrates. The careful design and evaluation of this manganese complex has the potential to offer an effective non-toxic 3d metal electrocatalyst, provided that common transition metal behaviors, such as disproportionation or carbon-metal bond formation, are avoided. Initial characterization of the complex by cyclic voltammetry (CV) demonstrates general reversibility of the catalyst, while additions of benzyl halide exhibit the execution of the electron transfer and catalytic step. Electrochemical simulations run in parallel with CV experiments provide supplementary guidance into the relationship between the substrate and catalyst. Additional studies conducted using bulk electrolysis, mass spectrometry, nuclear magnetic resonance, and density functional theory (DFT) calculation will help to further characterize the mechanism and supporting details. Elucidation of the catalytic mechanism will allow us to use this electrocatalyst in a series of synthetic organic conditions and aid in our advancement toward sustainable organometallic catalysis.

Electroreductive Cross‐Electrophile Coupling of Aromatic Carbonyl Compounds and Alkyl Bromides

AbstractClassical methods for the synthesis of tertiary alcohols mainly rely on the nucleophilic addition of organometallic reagents to carbonyl compounds. Here, we disclose a strategy for synthesizing tertiary alcohols via electroreductive cross‐electrophile coupling of aromatic carbonyl compounds and alkyl bromides (allyl, propargyl, benzyl and cyclohexyl bromides). This procedure features good substrate tolerance and friendly conditions (undivided cell, cheap and reusable carbon electrodes, reaction in open air, room temperature, without any external transition metal/activating reagent). Using this method, 32 desired products can be obtained with moderate to good yields, and gram‐scale synthesis is feasible, demonstrating the practicality of this approach.

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.

Synthesis of metal-free benzimidazole-based catalysts and its application in CO2 cycloaddition.

Ionic polymers functionalized with hydroxyl, carboxyl, and amino groups can enhance the catalytic activity of catalysts. However, the straightforward preparation of bifunctional ionic polymers containing abundant ionic active sites and hydrogen bond donors remains challenging. In this study, a series of porous ionic polymers (BZIs) containing different hydrogen bond donors (-NH2, -OH, -COOH) were prepared through a simple one-pot Friedel-Crafts alkylation using benzimidazole derivatives and benzyl bromide. The structures and properties of BZIs were characterized by various techniques such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, solid-state nuclear magnetic resonance, and scanning electron microscopy. Among the prepared catalysts (BZI-NH2, BZI-OH, and BZI-COOH), BZI-NH2 exhibited the highest catalytic activity and recyclability, achieving a yield of 97% in the CO2 cycloaddition. The synergistic effect of Br-, hydrogen bond donors (-NH-, -NH2), and N+ in BZI-NH2 was found to contribute to its superior catalytic performance. DFT calculations were employed to study the effect of hydrogen bonds, Br-, and N+ in BZI-NH2 and BZI-OH on the CO2 cycloaddition. Using BZI-NH2 as an example, a mechanism was proposed for the synergistic effect between amino groups and bromide ions in catalyzing the CO2 cycloaddition reaction.

Recognition of screening out hierarchical toxic contaminants tuned by quantified pseudo-components from complex engineering co-combustion

Co-combustion of industrial and municipal solid wastes has emerged as the most promising disposal technology, yet its effect on unknown contaminants generation remains rarely revealed due to waste complexity. Hence, six batches of large-scale engineering experiments were designed in an incinerator of 650 t/d, which overcame the inauthenticity and deviation of laboratory tests. 953–1772 non-targeted compounds were screened in fly ash. Targeting the impact of co-combustion, a pseudo-component matrix model was innovatively integrated to quantitatively extract nine components from complex wastes grouped into biomass and plastic. Thus, the influence was evaluated across eight dimensions, covering molecular characteristics and toxicity. The effect of co-combustion with biomass pseudo-components was insignificant. However, co-combustion with high ratios of plastic pseudo-components induced higher potential risks, significantly promoting the formation of unsaturated hydrocarbons, highly unsaturated compounds (DBE≥15), and cyclic compounds by 19 %− 49 %, 17 %− 31 %, and 7 %− 27 %, respectively. Especially, blending with high ratios of PET plastic pseudo-components produced more species of contaminants. Unique 2 Level I toxicants, bromomethyl benzene and benzofuran-2-carbaldehyde, as well as 4 Level II toxicants, were locked, receiving no concern in previous combustion. The results highlighted risks during high proportion plastics co-combustion, which can help pollution reduction by tuning source wastes to enable healthy co-combustion.

Cooperative Catalytic Coupling of Benzyl Chlorides and Bromides with Electron-Deficient Alkenes.

Benzyl radicals are an important class of intermediate. The use of visible light to generate them directly from their respective halides is an ideal synthetic strategy. The central impediment associated with their direct single-electron reduction (photo- or electro-) lies in their highly variable and structurally dependent reduction potential, which combine to make the identification of a general set of conditions difficult. Herein, we have employed a strategy of nucleophilic cooperative catalysis in which catalytic lutidine undergoes halide substitution, which decreases and levels the reduction potential. This allows a general set of photocatalytic conditions to transform a broad range of benzyl halides into radicals that can be used in the synthesis of more complex molecules, exemplified here by Giese coupling with electron-deficient alkenes.

Nucleophilic fluorine substitution reaction of α-carbonyl benzyl bromide, phenylthiofluoroalkyl bromide, and 2-bromo-2-phenoxyacetonitrile.

We herein describe a new method for nucleophilic fluorine substitution of alkylbromides using Et3N·3HF. The process is characterized by a broad substrate scope, good functional-group compatibility, and mild conditions and provides a variety of alkylfluorides including tertiary alkylfluorides that are versatile and structurally attractive.

Highly Efficient One-pot Electrosynthesis of Oxime Ethers from NOx over Ultrafine MgO Nanoparticles Derived from Mg-based Metal-Organic Frameworks.

Oxime ethers are attractive compounds in medicinal scaffolds due to the biological and pharmaceutical properties, however, the crucial and widespread step of industrial oxime formation using explosive hydroxylamine (NH2OH) is insecure and troublesome. Herein, we present a convenient method of oxime ether synthesis in a one-pot tandem electrochemical system using magnesium based metal-organic framework-derived magnesium oxide anchoring in self-supporting carbon nanofiber membrane catalyst (MgO-SCM), the in situ produced NH2OH from nitrogen oxides electrocatalytic reduction coupled with aldehyde to produce 4-cyanobenzaldoxime with a selectivity of 93 % and Faraday efficiency up to 65.1 %, which further reacted with benzyl bromide to directly give oxime ether precipitate with a purity of 97 % by convenient filtering separation. The high efficiency was attributed to the ultrafine MgO nanoparticles in MgO-SCM, effectively inhibiting hydrogen evolution reaction and accelerating the production of NH2OH, which rapidly attacked carbonyl of aldehydes to form oximes, but hardly crossed the hydrogenation barrier of forming amines, thus leading to a high yield of oxime ether when coupling benzyl bromide nucleophilic reaction. This work highlights the importance of kinetic control in complex electrosynthetic organonitrogen system and demonstrates a green and safe alternative method for synthesis of organic nitrogen drug molecules.

Highly Efficient One‐pot Electrosynthesis of Oxime Ethers from NOx over Ultrafine MgO Nanoparticles Derived from Mg‐based Metal‐Organic Frameworks

AbstractOxime ethers are attractive compounds in medicinal scaffolds due to the biological and pharmaceutical properties, however, the crucial and widespread step of industrial oxime formation using explosive hydroxylamine (NH2OH) is insecure and troublesome. Herein, we present a convenient method of oxime ether synthesis in a one‐pot tandem electrochemical system using magnesium based metal‐organic framework‐derived magnesium oxide anchoring in self‐supporting carbon nanofiber membrane catalyst (MgO‐SCM), the in situ produced NH2OH from nitrogen oxides electrocatalytic reduction coupled with aldehyde to produce 4‐cyanobenzaldoxime with a selectivity of 93 % and Faraday efficiency up to 65.1 %, which further reacted with benzyl bromide to directly give oxime ether precipitate with a purity of 97 % by convenient filtering separation. The high efficiency was attributed to the ultrafine MgO nanoparticles in MgO‐SCM, effectively inhibiting hydrogen evolution reaction and accelerating the production of NH2OH, which rapidly attacked carbonyl of aldehydes to form oximes, but hardly crossed the hydrogenation barrier of forming amines, thus leading to a high yield of oxime ether when coupling benzyl bromide nucleophilic reaction. This work highlights the importance of kinetic control in complex electrosynthetic organonitrogen system and demonstrates a green and safe alternative method for synthesis of organic nitrogen drug molecules.

Trifluoromethanesulfonate salt of 5,10,15,20-tetrakis(1-benzylpyridin-1-ium-4-yl)-21H,23H-porphyrin and its CaII complex

The synthesis, crystallization and characterization of a trifluoromethanesulfonate salt of 5,10,15,20-tetrakis(1-benzylpyridin-1-ium-4-yl)-21H,23H-porphyrin, C68H54N8 4+·4CF3SO3 −·4H2O, 1·OTf, are reported in this work. The reaction between 5,10,15,20-tetrakis(pyridin-4-yl)-21H,23H-porphyrin and benzyl bromide in the presence of 0.1 equiv. of Ca(OH)2 in CH3CN under reflux with an N2 atmosphere and subsequent treatment with silver trifluoromethanesulfonate (AgOTf) salt produced a red–brown solution. This reaction mixture was filtered and the solvent was allowed to evaporate at room temperature for 3 d to give 1·OTf. Crystal structure determination by single-crystal X-ray diffraction (SCXD) revealed that 1·OTf crystallizes in the space group P21/c. The asymmetric unit contains half a porphyrin molecule, two trifluoromethanesulfonate anions and two water molecules of crystallization. The macrocycle of tetrapyrrole moieties is planar and unexpectedly it has coordinated CaII ions in occupational disorder. This CaII ion has only 10% occupancy (C72H61.80Ca0.10F12N8O16S4). The pyridinium rings bonded to methylene groups from porphyrin are located in two different arrangements in almost orthogonal positions between the plane formed by the porphyrin and the pyridinium rings. The crystal structure features cation...π interactions between the CaII atom and the π-system of the phenyl ring of neighboring molecules. Both trifluoromethanesulfonate anions are found at the periphery of 1, forming hydrogen bonds with water molecules.

Harnessing redox-inactive rare-earth metals for photocatalytic reductive coupling of benzyl bromides

Compared with rare and expensive late-transition metals, rare-earth photocatalysts are much less investigated in synthetic chemistry, particularly concerning redox-inactive rare-earth metals. Herein, we describe a general strategy to realize the redox-inactive rare-earth photocatalysis by grafting a light-absorbing scaffold onto common ligands in rare-earth organometallics. Three guanidinate rare-earth complexes with photocatalytic functions were synthesized and found to exhibit higher catalytic efficiency than phenothiazine in the reductive homocoupling of benzyl bromides. These preliminary results illustrated that our “grafting” strategy could serve as a facile methodology for the construction of redox-inactive rare-earth photocatalysis systems.

Reactions of Platinum Terminal Polyynyl Complexes trans-(C6F5)(p-tol3P)2Pt(C≡C)nH (n = 2-4) and n-BuLi, Generation of Functional Equivalents of Pt(C≡C)nLi Species, and Derivatization with Organic and Inorganic Electrophiles.

Reactions of the title complexes and n-BuLi (1.5 equiv, -45 °C) afford functional equivalents of the deprotonated species trans-(C6F5)(p-tol3P)2Pt(C≡C)nLi (n = 2-4), as assayed by subsequent additions of MeI or Me3SiCl to give trans-(C6F5)(p-tol3P)2Pt(C≡C)nMe (66-52%) or trans-(C6F5)(p-tol3P)2Pt(C≡C)nSiMe3 (63-49%). However, 31P NMR data suggest more complicated mechanistic scenarios, and small amounts of the hydride complex trans-(C6F5)(p-tol3P)2PtH (independently synthesized from the chloride complex, AgClO4, and NaBH4) are detected in most cases. Analogous sequences involving trans-(C6F5)(p-tol3P)2Pt(C≡C)2H and benzyl bromide, D2O, or W(CO)6/Me3O+ BF4- similarly afford products with Pt(C≡C)2Bn, Pt(C≡C)2D, or Pt(C≡C)2C(OCH3)=W(CO)5 linkages. The crystal structures of the tungsten and corresponding SiMe3 adduct, the three Pt(C≡C)nMe species, and hydride complex are determined.

Palladium-catalyzed asymmetric carbene coupling en route to inherently chiral heptagon-containing polyarenes.

Developing facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial. However, originate chirality from the distorted structure around heptagon-containing polyarenes is largely overlooked, the enantioselective construction of all-carbon heptagon-containing polyarenes remains a challenge. Herein, we present a highly enantioselective synthesis route for fabricating all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross-coupling of benzyl bromides and N-arylsulfonylhydrazones. A wide range of nonplanar, saddle-shaped tribenzocycloheptene derivatives are efficiently prepared in high yields with excellent enantioselectivities using this approach. In addition, stereochemical stability experiments show that these saddle-shaped tribenzocycloheptene derivatives have high inversion barriers.

Divergent total synthesis of sesquiterpene (hydro)quinone meroterpenoids dysideanones A and E–G

The first total synthesis of marine sesquiterpene (hydro)quinone meroterpenoids dysideanones A and E–G (1 and 4–6) has been accomplished in an enantioselective and divergent way. The sesquiterpene fragment and the aromatic moiety were efficiently connected via a site-selective and diastereoselective intermolecular alkylation of Wieland–Miescher ketone derivative 9 and benzyl bromide 10. The core 6/6/6/6-fused backbone of dysideanones was efficiently constructed through an intramolecular radical cyclization reaction. Dysideanone G (6) was easily prepared on a gram-scale and dysideanones A, E, and F (1, 4, and 5) were divergently transformed from dysideanone G (6) in one or two steps

Effect of fluorination on the cytotoxic potentials of benzimidazolium-based N-heterocyclic carbene ligands and their silver(I) complexes

The current study reports a new series of fluorinated benzimidazolium salts and their silver(I) complexes. The ligands were prepared via N-alkylation of 1-decylbenzimidazole with benzyl/fluorinated benzyl bromides. In situ deprotonation of the salts with silver oxide and metathesis reaction with potassium hexafluorophosphate yielded the mononuclear silver(I)–NHC complexes. All compounds were characterized using FTIR and NMR spectroscopies, CHN elemental analysis and liquid chromatography-time-of-flight mass spectrometry (LCMS-TOF). The in vitro cytotoxic activities of the ligands and complexes against human cervical cancer (HeLa), estrogen-positive human breast cancer (MCF-7) and triple-negative human breast cancer (MDA-MB-231) cells were evaluated using the MTT assay. All compounds exhibited remarkable growth inhibition against these cells, superior to etoposide, a clinical anticancer drug. Fluorination exerted different growth inhibition effects against HeLa, MDA-MB-231 and MCF-7 cells. Fluorination modulated the growth inhibition potencies of the salts and complexes against HeLa but had no enhancement effect against MCF-7 and MDA-MB-231. Incorporating silver(I) ions enhanced the cytotoxicity of the complexes against all tested cell lines (IC50: 0.46–1.36 µM).

Utilization of High-Throughput Experimentation (HTE) and ChemBeads Toward the Development of an Aryl Bromide and Benzyl Bromide Photoredox Cross-Electrophile Coupling.

The discussion herein describes a metallaphotoredox reaction that allows for efficient exploration of benzyl structure-activity relationships in medicinal chemistry. The use of HTE (high-throughput experimentation) and ChemBeads allows for rapid reaction optimization. The formation of di(hetero)arylmethanes via cross-electrophile coupling between aryl bromides and benzyl bromides provides access to diverse chemical space. The breadth of the substrate scope will be discussed, along with the utilization of batch photochemistry for the preparation of this di(hetero)arylmethane motif on a larger scale.