Alkyl Bromides Research Articles

A highly effective method for the environmentally friendly production of novel chromene derivatives using electron deficient compounds

AbstractNew, high‐yield derivatives of oxepino[3,2‐c]chromene were synthesized through a multicomponent reaction. This reaction involved 2‐hydroxyacetophenone, dimethyl carbonate, activated acetylenic compounds, and alkyl bromide. The reaction took place at room temperature in an aqueous environment, resulting in the formation of these innovative compounds. Oxathiepines were synthesized using multicomponent reactions of 2‐hydroxyacetophenone, dimethyl carbonate, isothiocyanate, and alkyl bromide in water at room temperature. This technology offers several benefits, including quick response times, high product yields, and easy product separation using straightforward techniques.

Metallaphotoredox deuteroalkylation utilizing thianthrenium salts

Deuterium labeling compounds play a crucial role in organic and pharmaceutical chemistry. The synthesis of such compounds typically involves deuterated building blocks, allowing for the incorporation of deuterium atoms and functional groups into a target molecule in a single step. Unfortunately, the limited availability of synthetic approaches to deuterated synthons has impeded progress in this field. Here, we present an approach utilizing alkyl-substituted thianthrenium salts that efficiently and selectively introduce deuterium at the α position of alkyl chains through a pH-dependent HIE process, using D2O as the deuterium source. The resulting α-deuterated alkyl thianthrenium salts, which bear two deuterium atoms, exhibit excellent selectivity and deuterium incorporation in electrophilic substitution reactions. Through in situ formation of isotopically labelled alkyl halides, these thianthrenium salts demonstrate excellent compatibility in a series of metallaphotoredox cross-electrophile coupling with (hetero)aryl, alkenyl, alkyl bromides, and other alkyl thianthrenium salts. Our technique allows for a wide range of substrates, high deuterium incorporation, and precise control over the site of deuterium insertion within a molecule such as the benzyl position, allylic position, or any alkyl chain in between, as well as neighboring heteroatoms. This makes it invaluable for synthesizing various deuterium-labeled compounds, especially those with pharmaceutical significance.

Influence of paternal factors on plastic ingestion and brominated chemical exposure in East Tropical Atlantic Procellariid chicks

The presence of plastic debris and organo-brominated compounds in the marine environment poses a concern to wildlife. Plastic can absorb and release chemical compounds, making their ingestion potentially harmful, while chemical compounds have become omnipresent, with a tendency to bioaccumulate in the food web. Seabirds are often used as indicators of marine plastic pollution, yet studies on the exposure of tropical communities to plastic contamination are still scarce. In this study we monitored the amounts of plastics in faeces and organo-brominated compounds ingested/assimilated in feathers by adults and chicks of Cape Verde shearwaters and Bulwer's petrels from Cabo Verde. Anthropogenic pollutants, polybrominated diphenyl ethers (PBDEs), and naturally generated methoxylated-PBDEs (MeO-PBDEs) were among the probed compounds. The frequency of plastic debris ingestion was similar in both species' adults and chicks, although, the characteristics of the ingested plastic differed. Frequency and number of microplastics increased throughout the nestling season for chicks from both species. All species and age groups showed the presence of PBDEs and MeO-PBDEs. Among PBDEs, Bulwer's petrels exhibited higher concentrations than Cape Verde shearwaters, and chicks had higher concentration profiles than adults. Specifically, Bulwer's petrel chicks showed higher concentrations than Cape Verde shearwater chicks. On the contrary, Cape Verde shearwater adults exhibited higher occurrence and concentrations of MeO-PBDEs when compared to Cape Verde shearwater chicks. We found no effect of plastic loadings or loadings of organohalogen contaminants on body condition or size, although harmful effects may be hidden or reveal themselves in a medium- to long-term. Feather samples from both adults and chicks were shown to be useful for comparing intraspecific contamination levels and appear suitable for the long-term assessment of organohalogen contaminants in seabirds. Species-specific foraging and feeding strategies are likely the drivers of the observed variation in organochlorine contamination burdens among seabird species.

Manganese-Catalyzed Carbonylation of Unactivated Alkyl Bromides with Alkylidenecyclopropanes

Manganese-Catalyzed Carbonylation of Unactivated Alkyl Bromides with Alkylidenecyclopropanes

Repurposing of halogenated organic pollutants via alkyl bromide-catalysed transfer chlorination.

Halogenated organic pollutants (HOPs) are causing a significant environmental and human health crisis due to their high levels of toxicity, persistence and bioaccumulation. Urgent action is required to develop effective approaches for the reduction and reuse of HOPs. Whereas current strategies focus primarily on the degradation of HOPs, repurposing them is an alternative approach, albeit a challenging task. Here we discover that alkyl bromide can act as a catalyst for the transfer of chlorine using alkyl chloride as the chlorine source. We demonstrate that this approach has a wide substrate scope, and we successfully apply it to reuse HOPs that include dichlorodiphenyltrichloroethane, hexabromocyclododecane, chlorinated paraffins, chloromethyl polystyrene and poly(vinyl chloride) (PVC). Moreover, we show that the synthesis of essential non-steroidal anti-inflammatory drugs can be achieved using PVC and hexabromocyclododecane, and we demonstrate that PVC waste can be used directly as a chlorinating agent. Overall, this methodology offers a promising strategy for repurposing HOPs.

Nickel-Catalyzed Four-Component Carbonylation of 1,3-Butadiene To Access β,γ-Unsaturated Ketones.

A new strategy to obtain β,γ-unsaturated ketones via the cross-coupling of 1,3-butadiene, alkyl bromides, and arylboronic acids under 1 bar of CO with nickel as the catalyst has been developed. This newly developed four-component carbonylation procedure features advantages including using a cheap catalytic system, high step economy, mild reaction conditions, and excellent 1,4-regioselectivity, thereby providing a sustainable and alternative tool for β,γ-unsaturated ketones production compared to the present tactics. To elucidate the application potential of this method, olefin synthons are derived from the representative coupling product.

Raman Monitoring of the Electro-Optical Synergy-Induced Enhancements in Carbon-Bromine Bond Cleavage, Reaction Rate, and Product Selectivity of p-Bromothiophenol.

Electro-optical synergy has recently been targeted to improve the separation of hot carriers and thereby further improve the efficiency of plasmon-mediated chemical reactions (PMCRs). However, the electro-optical synergy in PMCRs needs to be more deeply understood, and its contribution to bond dissociation and product selectivity needs to be clarified. Herein, the electro-optical synergy in plasmon-mediated reduction of p-bromothiophenol (PBTP) was studied on a plasmonic nanostructured silver electrode using in situ Raman spectroscopy and theoretical calculations. It was found that the electro-optical synergy-induced enhancements in the cleavage of carbon-bromine bonds, reaction rate, and product selectivity (4,4'-biphenyl dithiol vs thiophenol) were largely affected by the applied bias, laser wavelength, and laser power. The theoretical simulation further clarified that the strong electro-optical synergy is attributed to the matching of energy band diagrams of the plasmonic silver with those of the adsorbed PBTP molecules. A deep understanding of the electro-optical synergy in PBTP reduction and the clarification of the mechanism will be highly beneficial for the development of other highly efficient PMCRs.

Phytic Acid-Promoted Deposition of Gold Nanoparticles with Grafted Cationic Polymer Brushes for the Construction of Synergistic Contact-Killing and Photothermal Bactericidal Coatings.

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.

Mild Strategy for the Preparation of Alkyl Sulfonyl Fluorides from Alkyl Bromides and Alcohols Using Photoredox Catalysis and Flow Chemistry.

Facile access to sp3-rich scaffolds containing a sulfonyl fluoride group is still limited. Herein, we describe a mild and scalable strategy for the preparation of alkyl sulfonyl fluorides from readily available alkyl bromides and alcohols using photoredox catalysis. This approach is based on halogen atom transfer (XAT), followed by SO2 capture and fluorination. The method features mild conditions enabling fast access to high-value derivatives and has been scaled up to 5 g using a continuous stirred tank reactor cascade.

Visible‐Light‐Mediated Alkylation of N‐Heteroarenes Using 2‐Mercaptothiazolinium Salts as Alkyl Radical Source

A visible‐light‐mediated radical heteroarylation of 2‑mercaptothiazolinium salts with N‐heteroarenes is reported, furnishing the corresponding functionalized N‐heteroarenes in good to high yields. Various alkyl bromides were converted conveniently into redox‐active thiazolinium salts and subsequently into alkyl radicals by reaction with an excited‐state photocatalyst. This mild protocol permits efficient functionalization of various N‐heteroarenes with a wild range of cyclic and acyclic primary and secondary alkyl groups.

Efficient Functionalization of Organosulfones via Photoredox Catalysis: Direct Incorporation of α-Carbonyl Alkyl Side Chains into α-Allyl-β-Ketosulfones.

A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-β-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis.

Stereoselective Nucleophilic Halogenation at CF3-Substituted Nonclassical Carbocation.

CF3-substituted cyclopropyl carbinol derivatives undergo regioselective and diastereoselective nucleophilic halogenation at the quaternary carbon center to provide acyclic products as a single diastereomer. The selectivity of the substitution is rationalized by the formation of a nonclassical cyclopropylcarbinyl cation intermediate, reacting at the most-substituted carbon center. Tertiary alkyl chlorides, bromides, and fluorides adjacent to a stereogenic C-CF3-motif are diastereomerically pure and can be obtained in few catalytic steps from commercially available alkynes.

Influence of titanium dioxide nanotubes with alkyl ammonium alkyl bromide on the physicochemical properties and adhesion of experimental adhesive resins to dentin

ObjectiveThis study evaluated the effect of the incorporation of titanium dioxide nanotubes with alkyl trimethyl ammonium bromide (ntTiO2/ATAB) into experimental adhesive resins on their physicochemical properties and adhesion to dentin. Materials & methodsThe experimental adhesive resins were formulated with 66.66 wt% Bis-GMA and 33.33 wt% HEMA, photoinitiator with addition of ntTiO2/ATAB (1:1) in different concentrations: G1%, G2.5%, and G5%. One groups with no ntTiO2/ATAB addition was used as control (G0%). An optical tensiometer was used to analyze the contact angle (COA) by the sessile drop method (distilled water and α-bromonaphthalene) (n = 5), while the surface free energy (SFE) was calculated using Owens-Wendt-Rabel-Kaelble method. Flexural strength (FS) test (three-point bending) of polymerized adhesive samples was performed according to ISO 4049:2019 (n = 10) after 24 h or one year of water storage at 37 °C, as well as for the microtensile bond strength (μTBS) test, in which a commercial adhesive (GSBMP) was also used as control (n = 10). The adhesive-dentin interfaces were evaluated by scanning electron microscopy and X-ray spectrometry (n = 5). Data were analyzed by one-way (COA and SFE), two-way (FLE and μTBS) ANOVA and Tukey's test (α = 0.05). ResultsG5% showed the highest COA with nonpolar liquid and higher SFE than G0%. The G5% showed decreased FS compared to G0%. The μTBS of both controls (G0% and GSBMP) decreased after one year. TiO2/ATAB-containing adhesives to dentin showed no significant decrease after one year. All adhesives formed hybrid layer and the resin tags inside the dentinal tubules. ConclusionsThe incorporation of 1 and 2.5% of ntTiO2/ATAB into experimental adhesive resins did not impar the SFE. After one year, any concentration of ntTiO2/ATAB reduced the FS compared with control, but did not impair the μTBS.

Anion exchange membranes derived from poly(ionic liquid) of poly(bis-piperidinium) and polybenzimidazole blends

Anion exchange membranes (AEMs) play a critical role in various environmentally friendly electrochemical energy conversion and storage devices such fuel cells, water electrolysis and flow batteries. Recently, AEMs based on ether-free ionomers or ionenes have attracted much attention due to their excellent alkaline stabilities, however normally suffering from multiple-step synthetic procedure, post-functionalization and the use of precious metal catalysts. In this study, we develop a facile method to synthesize bis-piperidinium main-chain poly(ionic liquid)s devoid of ether linkages through the nucleophilic reaction between a bis-piperidine monomer of 4,4′-trimethylene bis(1-methyl-piperidine) and various bifunctional alkyl or aryl bromides. Seven poly(ionic liquid)s of poly(bis-alkyl piperidinium) are subsequently blended with polybenzimidazole (PBI) to give mechanically robust and dimensionally stable AEMs. The membrane performances are readily adjusted by changing the chemical structure of poly(bis-alkyl piperidinium)s. The membrane based on the poly(bis-alkyl piperidinium) containing a flexible butylidene spacer chain achieves the highest Br- conductivity of 67 mS cm−1 at 80 °C, tensile strength of around 13 MPa at room temperature, and a superior alkaline stability in 1 mol/L KOH at 60 °C during 1250 h. Density functional theory calculations further support the enhanced alkaline stability of the piperidinium cation with alkyl group compared with the one with benzyl group.

Alkyl Radical Initiated Cyclization/Cascade for Synthesizing Lactam‐Substituted Alkyl Sulfones

Comprehensive SummaryAn alkyl radical initiated cyclization/tandem reaction of alkyl bromides and alkyl electrophiles by using potassium metabisulphite (K2S2O5) as a connector is developed for the synthesis of various lactam‐substituted alkyl sulfones. Notably, this process does not require a metal catalyst or metal powder reductant, highlighting its environmentally friendly features. The reaction demonstrates outstanding substrate adaptability and a high tolerance towards diverse functional groups. Furthermore, the biologically active molecules and commercially available drugs with a late‐stage modification are also highly compatible with this transformation. Mechanistic studies revealed that the reaction proceeds through a single‐step process involving intramolecular radical cyclization, "SO2" insertion, and external alkyl incorporation.

Metal‐Free and NBS‐Mediated C(sp3)−S Bond Cleavage of Thioethers to Access Alkyl Bromides

AbstractA selective C(sp3)−S bond cleavage of thioethers mediated by NBS is developed. Various alkyl bromides have been obtained in good yields using N‐aryl‐3‐(methylthio)propanamides and arylmethylene alkylthioethers. Mechanistic studies suggest that the formation of 3‐bromo‐N‐arylpropanamides may involve sulfoxide intermediates, while the arylmethylene bromides are formed through direct bromination process mediated by NBS. The significance of this strategy lies in its pioneering use of NBS for C−S bond cleavage and subsequent bromination reaction.

Electrochemical Nickel‐Catalyzed Hydrogenation

AbstractOlefin hydrogenation is one of the most important transformations in organic synthesis. Electrochemical transition metal‐catalyzed hydrogenation is an attractive approach to replace the dangerous hydrogen gas with electrons and protons. However, this reaction poses major challenges due to rapid hydrogen evolution reaction (HER) of metal‐hydride species that outcompetes alkene hydrogenation step, and facile deposition of the metal catalyst at the electrode that stalls reaction. Here we report an economical and efficient strategy to achieve high selectivity for hydrogenation reactivity over the well‐established HER. Using an inexpensive and bench‐stable nickel salt as the catalyst, this mild reaction features outstanding substrate generality and functional group compatibility, and distinct chemoselectivity. In addition, hydrodebromination of alkyl and aryl bromides could be realized using the same reaction system with a different ligand, and high chemoselectivity between hydrogenation and hydrodebromination could be achieved through ligand selection. The practicability of our method has been demonstrated by the success of large‐scale synthesis using catalytic amount of electrolyte and a minimal amount of solvent. Cyclic voltammetry and kinetic studies were performed, which support a NiII/0 catalytic cycle and the pre‐coordination of the substrate to the nickel center.

Electrochemical Nickel-Catalyzed Hydrogenation.

Olefin hydrogenation is one of the most important transformations in organic synthesis. Electrochemical transition metal-catalyzed hydrogenation is an attractive approach to replace the dangerous hydrogen gas with electrons and protons. However, this reaction poses major challenges due to rapid hydrogen evolution reaction (HER) of metal-hydride species that outcompetes alkene hydrogenation step, and facile deposition of the metal catalyst at the electrode that stalls reaction. Here we report an economical and efficient strategy to achieve high selectivity for hydrogenation reactivity over the well-established HER. Using an inexpensive and bench-stable nickel salt as the catalyst, this mild reaction features outstanding substrate generality and functional group compatibility, and distinct chemoselectivity. In addition, hydrodebromination of alkyl and aryl bromides could be realized using the same reaction system with a different ligand, and high chemoselectivity between hydrogenation and hydrodebromination could be achieved through ligand selection. The practicability of our method has been demonstrated by the success of large-scale synthesis using catalytic amount of electrolyte and a minimal amount of solvent. Cyclic voltammetry and kinetic studies were performed, which support a NiII/0 catalytic cycle and the pre-coordination of the substrate to the nickel center.

Halogen-Bond-Promoted Direct Cross-Coupling of Trifluoromethylated Alkyl Bromides with Coumarins/Quinolinones: Unraveling Trifluoromethyl Effects.

This study introduces a novel approach involving XB-mediated cross-coupling of α-trifluoromethylated alkyl bromides with coumarins and quinolinones under visible light irradiation. Both density functional theory (DFT) calculations and experimental studies converge to suggest that the noncovalent interaction between alkyl bromides and DMAP, intensified by the α-trifluoromethyl group, plays a pivotal role in facilitating this chemoselective reaction.

Enantioselective domino alkyl arylation of vinyl phosphonates by combining photoredox and nickel catalysis

A nickel/photoredox mediated asymmetric domino alkyl arylation of vinyl phosphonates to generate a diverse array of enantioenriched α-aryl phosphonates is disclosed. This asymmetric three-component difunctionalization couples aryl halides and alkyl bromides with vinyl phosphonates, exhibiting excellent chemo- and regioselectivity under mild reaction conditions. The method avoids the need for pre-formed organometallics and phosphorus halides. Mechanistic and DFT studies suggest that photoexcited [4CzIPN]* oxidizes diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate (HEH) to generate the [4CzIPN]•–, which then reduces the alkyl bromide to form alkyl radicals that undergo Giese addition to the vinyl phosphonate. At the same time, Ni0 oxidatively adds the aryl bromide followed by enantiodetermining oxidative radical trapping of the phosphonate-based radical by the tetrahedral NiII center followed by reductive elimination. Independent gradient model based on Hirshfeld partition (IGMH) analysis suggests that the orientation of the phosphonate group (P=O…π interaction) is expected to play an essential role in controlling the enantioselectivity.