Alkyl Halides Research Articles

Enantioselective Three‐Component α‐Allylic Alkylation of α‐Amino Esters by Synergistic Photoinduced Pd/Carbonyl Catalysis

Photoinduced excited‐state Pd catalysis has emerged as an intriguing strategy for unlocking new reactivity potential of simple substrates. However, the related transformations are still limited and the enantiocontrol remains challenging. Organocatalysis displays unique capability in substrate activation and stereocontrol. Combination of organocatalysis and photoinduced excited‐state Pd catalysis may provide opportunities to develop new enantioselective reactions from simple substrates. By applying cooperative triple catalysis including excited‐state Pd catalysis, ground‐state Pd catalysis, and carbonyl catalysis, we have successfully realized enantioselective α‐allylic alkylation of α‐amino esters with simple styrene and alkyl halide starting materials. The reaction allows rapid modular assembly of the three reaction partners into a variety of chiral quaternary α‐amino esters in good yields with 90‐99% ee, without protecting group manipulations at the active NH2 group. The cooperation of the chiral pyridoxal catalyst and the chiral phosphine ligand accounts for the excellent chirality induction.

Enantioselective Three‐Component α‐Allylic Alkylation of α‐Amino Esters by Synergistic Photoinduced Pd/Carbonyl Catalysis

Photoinduced excited‐state Pd catalysis has emerged as an intriguing strategy for unlocking new reactivity potential of simple substrates. However, the related transformations are still limited and the enantiocontrol remains challenging. Organocatalysis displays unique capability in substrate activation and stereocontrol. Combination of organocatalysis and photoinduced excited‐state Pd catalysis may provide opportunities to develop new enantioselective reactions from simple substrates. By applying cooperative triple catalysis including excited‐state Pd catalysis, ground‐state Pd catalysis, and carbonyl catalysis, we have successfully realized enantioselective α‐allylic alkylation of α‐amino esters with simple styrene and alkyl halide starting materials. The reaction allows rapid modular assembly of the three reaction partners into a variety of chiral quaternary α‐amino esters in good yields with 90‐99% ee, without protecting group manipulations at the active NH2 group. The cooperation of the chiral pyridoxal catalyst and the chiral phosphine ligand accounts for the excellent chirality induction.

Pnictogen and Chalcogen Salts as Alkylating Agents.

Alkylation reactions and their products are considered crucial in various contexts. Synthetically, the alkylation of a nucleophile is usually promoted using hazardous alkyl halides. Here, we aim to highlight the potential of pnictogen (ammonium or phosphonium) and chalcogen salts (sulfonium, selenonium, and telluronium) to function as alkylating agents. These compounds can be considered as non-volatile electrophilic alkyl reservoirs. We will center our discussion on the strategies developed in recent years to expand the synthetic utility of these salts in terms of transferable alkyl groups, substrate scope, and product selectivity.

Olefination of Activated Alkyl Halides with Phosphonium Salts

Olefination of Activated Alkyl Halides with Phosphonium Salts

Overcoming Copper Reduction Limitation in Asymmetric Substitution: Aryl-Radical-Enabled Enantioconvergent Cyanation of Alkyl Iodides.

Cu-catalyzed enantioconvergent cross-coupling of alkyl halides has emerged as a powerful strategy for synthesizing enantioenriched molecules. However, this approach is intrinsically limited by the weak reducing power of copper(I) species, which restricts the scope of compatible nucleophiles and necessitates extensive ligand optimization or the use of complex chiral scaffolds. To overcome these challenges, we introduce an aryl-radical-enabled strategy that decouples the alkyl halide activation step from the chiral Cu center. We demonstrate that merging aryl-radical-enabled iodine abstraction with Cu-catalyzed asymmetric radical functionalization enables the conversion of racemic α-iodoamides to enantioenriched alkyl nitrile products with good yield and enantioselectivity. The rational design of chiral ligands identified a new class of carboxamide-containing BOX ligands. Mechanistic studies support an aryl-radical-enabled pathway and the unique hydrogen-bonding ability in the newly designed BOX ligands. This aryl-radical-enabled asymmetric substitution reaction has the potential to significantly expand the scope of Cu-catalyzed enantioconvergent cross-coupling reactions.

Visible-Light-Mediated Vicinal Dihalogenation of Unsaturated C-C Bonds Using Dual-Functional Group Transfer Reagents.

The growing demand for chemical production continues to drive the development of sustainable and efficient methods for introducing molecular complexity. In this context, the exploration of unconventional functional group transfer reagents (FGTRs) has led to significant advancements in practical and atom-efficient synthetic protocols. Aiming to advance the field of valuable organic synthesis, herein we report the successful development of carbon-based, bench-stable, modular, and inexpensive reagents implemented in dual halogen transfer to unsaturated hydrocarbons via photocatalytic activation of reagents based on a radical-polar crossover mechanism. This method beneficially enables vicinal dichlorination, dibromination, and bromo-chlorination reactions of olefins, offering practical alternatives to the use of toxic binary halogens. Detailed mechanistic studies, combining experimental, spectroscopic, and theoretical investigations, revealed a distinctive photocatalytic single-electron transfer reduction of FGTR. This process triggers mesolytic carbon-halogen bond cleavage, followed by a radical 1,2-halide rearrangement, leading to the continuous generation of dihalogen species in the reaction medium. The wide applicability of the developed protocol is demonstrated through an extensive scope of unsaturated molecules, including additional operations on strain-release dihalogenation.

Marine Gastropod Planaxis sulcatus (Born, 1778) of Uvari Coastal Waters: A Comprehensive Study on Its Antibacterial Activity, Biochemical Composition and FTIR Spectroscopy

Diverse nutritional profiles and potent antimicrobial properties distinguish marine gastropods from other members of the phylum Mollusca. This study targets the investigation of the antibacterial activity, biochemical and FTIR analysis of ethanol extracts of marine gastropod mollusc Planaxis sulcatus. The well diffusion method was used to carry out the antibacterial assay. The extract showed the maximum inhibition (21±2 mm inhibitory zone) against the human bacterial pathogen S. aureus, whereas K. pneumonia showed the lowest susceptibility (12 mm). The extracts had MIC values between 0.21 and 1.04 mg/ml. The biochemical assay's findings revealed that the majority of the snail's flesh (51%) is made up of protein, with only 5% of the mass coming from carbohydrates and very trace amounts of fat (0.2%). The FTIR analysis represents the presence of alkyl halides, nitro compounds, aromatic compounds, alkynes, nitriles, carboxylic acid, aldehyde, alkanes and alcohol in the gastropod extracts. The aforementioned observational result demonstrates the abundance of antibacterial substances in the gastropod extracts. Further research is necessary to fully understand the structural composition of the antibacterial substances found in this marine snail.

Synthesis and Evaluation of New Type Plant Extraction Corrosion Inhibitor

The use of corrosion inhibitors in the development of oil and gas fields is an important means of effectively preventing metal corrosion, at present, the green growth of the oil and gas industry requires low-toxicity, low-residue, easy-to-post-treatment and other environmentally friendly corrosion inhibitors, however, most industrially used corrosion inhibitors such as mercury salts quaternary ammonium salts, and imidazolines are toxic to some degree. In this paper, a plant extract corrosion inhibitor was synthesized, firstly, the purple sweet potato extract was extracted by ethanol, and then the purple sweet potato extract and alkyl halide such as methane were used to produce the purple sweet potato corrosion inhibitor through condensation extraction and other processes, and the corrosion inhibitory performance of the inhibitor was evaluated by the loss-in-weight method, scanning electron microscopy, polarization curves, and impedance spectroscopy. The results show that there is a certain inhibition effect on N80 steel in the simulated stratum water environment, and the retardation rate can reach 91.38% in the gas phase, and the corrosion product morphology and chemical elements on the surface of N80 steel specimens were characterized by SEM, EDS, and it can be observed that a relatively dense protective film was formed after adding purple sweet potato corrosion inhibitor, and the corrosion inhibition rate can be known according to the weightlessness curve, Tafel curve and impedance curve. The corrosion inhibition rate increases with the increase of corrosion inhibitor concentration.

Anchoring atomic Pd on molybdenum disulfide with state-of-the-art specific activity in the electrochemical dehalogenation of florfenicol

The widespread discharge of halogenated organic pollutants (HOPs) in wastewater brings significant risks to the environment and human health due to potent high toxicity, antibacterial activity, and strong biodegradation resistance. Adsorbed atomic hydrogen (H*ads)-mediated electrocatalytic hydrodehalogenation (EHDH) has been recognized as an efficient strategy for HOPs removal through selectively breaking carbon-halogen bonds. In this work atomic Pd uniformly anchored on molybdenum disulfide (denoted as Pd-MoS2) was synthesized through a facile hydrothermal method and found with state-of-the-art specific activity in florfenicol (FLO) removal via the H*ads-mediated EHDH process. Pd-MoS2 completely dehalogenated (∼100 %) FLO within 30 min at a rate constant of 0.15 min−1, which was 6.0, 6.5 and 33.1 times the value of MoS2, Pd/C and carbon paper samples, respectively. Notably, the toxicity of the wastewater was reduced to 1/6 of its original value after the treatment. Moreover, Pd-MoS2 presented superior catalytic stability in five successive cycles. Furthermore, Pd-MoS2 was also robust in complex water environment with practical applicability for industrial wastewater treatment. A dual-active-center mechanism with enhanced H*ads production capacity and the improved H*ads utilization efficiency was contributed to the increased EHDH activity on Pd-MoS2.

A Direct Visible‐Light Mediated Coupling Of Azaarenes with Diversely Functionalized Alkyl Carbons via Organophotocatalytic Sp3C−H Bond Activation

AbstractSubstituted azaarenes are one of the most ubiquitous moieties in natural products and drug molecules. An efficient organophotocatalytic method for direct coupling of diverse cyclic and acyclic alkyl carbons of alcohols, ethers, alkyl halides and alkanes with different azaaryl systems has been developed. It uses low loading of easily synthesizable efficient acridinium based photocatalyst and blue LED to generate highly reactive radicals on saturated hydrocarbons through sequential single electron transfer (SET) and hydrogen atom transfer (HAT) process. These in situ generated nucleophilic carbon radicals then undergo instantaneous regio‐selective coupling with azaarenes through Minisci type coupling to generate an array of important pharmacophores through sp2C−sp3C bond formation. With inexpensive organophotocatalysts, higher yield and wide substrate scope, this method provides a greener, efficient and versatile alternative to the previously reported syntheses.

Direct Introduction of Perfluoroacyl (−CORF) Groups into Organic Substrates

AbstractThe direct addition of perfluoroacyl (−CORF) groups to organic frameworks has seen a resurgence in interest due to the benefits of these groups in late‐stage modification of pro‐drugs and biologically active compounds, helping to identify new active leads. The presence of −CORF groups positively impacts the structure‐activity relationships of these compounds. In that sense, both polar methods and radical protocols have been developed for the direct syntheses of trifluoromethyl and perfluoroalkyl ketones. In particular, methodologies to tame the unstable trifluoroacyl radical, which could be a key intermediate in the late‐stage syntheses of trifluoroacyl‐substituted compounds, has allowed much progress in this area. In the next sections, the direct incorporation of perfluoroacyl groups into (hetero)aromatic compounds, −CORF substitutions at Csp3−H, alkyl halides, alkenes, amides, and N‐atoms will be discussed in detail, suggesting the future directions and perspectives in the field. These known reactions are summarized in Table 1.

Exceptionally Short Tetracoordinated Carbon-Halogen Bonds in Hexafluorodihalocubanes.

Molecules that contain bonds whose length significantly deviates from the average are of interest in the context of understanding the nature and limits of the chemical bonds. However, it is difficult to disentangle the individual contributions of the multiple factors that give rise to such bond-length deviations as reports on such molecules remain scarce. In the present study, we have succeeded in synthesizing hexafluorodihalocubanes of the type C8F6X2 (2) (X = Cl (2Cl), Br (2Br), I (2I)), which represent a new series of molecules with unusual C(sp3)-halogen bonds. The C(sp3)-halogen bonds of 2Cl, 2Br, and 2I, determined via single-crystal X-ray diffraction analysis, are approximately 0.07-0.09 Å shorter than typical C(sp3)-halogen bonds. In particular, the carbon-iodine bonds of 2I are the shortest C(sp3)-I bonds reported to date. The solution-state structures and electronic states of the C(sp3)-halogen bonds in these hexafluorodihalocubanes were analyzed by X-ray absorption spectroscopy, which revealed detailed information on the length of these C(sp3)-halogen bonds in solution and the solid state as well as on the electron-deficient nature of 2. Detailed theoretical calculations and a comparison with halotrinitromethanes (1), which represent another series of molecules with shortened C(sp3)-halogen bonds, revealed that the factors responsible for the shortening of the C(sp3)-halogen bond vary among the different C(sp3)-halogen bonds, i.e., for C(sp3)-Cl and C(sp3)-Br, the s-character and hyperconjugation effects predominate, whereas for C(sp3)-I, the interatomic Coulombic interaction effect prevails.

C-H alkylation of heterocycles via light-mediated palladium catalysis.

Methods enabling direct C-H alkylation of heterocycles are of fundamental importance in the late-stage modification of natural products, bioactive molecules, and medicinally relevant compounds. However, there is a scarcity of a general strategy for the direct C-H alkylation of a variety of heterocycles using commercially available alkyl surrogates. We report an operationally simple palladium-catalyzed direct C-H alkylation of heterocycles using alkyl halides under the visible light irradiation with good scalability and functional group tolerance. Our studies suggest that the photoinduced alkylation proceeds through cascade of events comprising, site-selective alkyl radical addition, base-assisted deprotonation, and oxidation. A combination of experiments and computations was employed for the generalization of this strategy, which was successfully translated towards the modification of natural products and pharmaceuticals.

C‐H alkylation of heterocycles via light‐mediated palladium catalysis

Methods enabling direct C‐H alkylation of heterocycles are of fundamental importance in the late‐stage modification of natural products, bioactive molecules, and medicinally relevant compounds. However, there is a scarcity of a general strategy for the direct C‐H alkylation of a variety of heterocycles using commercially available alkyl surrogates. We report an operationally simple palladium‐catalyzed direct C‐H alkylation of heterocycles using alkyl halides under the visible light irradiation with good scalability and functional group tolerance. Our studies suggest that the photoinduced alkylation proceeds through cascade of events comprising, site‐selective alkyl radical addition, base‐assisted deprotonation, and oxidation. A combination of experiments and computations was employed for the generalization of this strategy, which was successfully translated towards the modification of natural products and pharmaceuticals.

Nickel-Catalyzed Photoredox Allenylation of Alkyl Halides.

We report a dual Ni/photoredox-catalyzed cross-coupling method for propargyl carbonates and nonactivated alkyl bromides, facilitating the synthesis of a variety of substituted allenes under mild and practical conditions. Mechanistically, the reaction integrates Ni-catalyzed activation of the propargyl electrophile via SN2' oxidative addition at Ni(I) with silyl radical-induced activation of the alkyl halide through halogen-atom transfer. This methodology provides a gentle approach for introducing allenyl groups into complex halogenated aliphatic molecules, offering further opportunities for derivatization.

Synthesis and characterization of two asymmetrical 2-cyclohexylsulfenyl-5-alkylsulfenyl[1,3,4]thiadiazoles and study the impact of substituents on the structural features, thermal behavior, and anti-bacterial activity

Regarding the importance of 1,3,4-thiadiazoles due to versatile biological activity and for investigation of the symmetry impact on thermal behavior and antibacterial activity of 2,5-bisalkylsulfenyl[1,3,4]thiadiazole, two new derivatives viz. 2-cyclohexylsulfenyl-5-cyclopentylsulfenyl[1,3,4]thiadiazole and 2-cyclohexylsulfenyl-5-dodecylsulfenyl[1,3,4]thiadiazole, were synthesized through the nucleophilic substitution reaction appropriate alkyl halide with 5-cyclohexyl-3H-[1,3,4]thiadiazole-2-thione in ethanol under reflux conditions. The chemical structure of the products was elucidated by the physical and spectroscopic techniques. After tedious work, the suitable snow-like crystals of 2-cyclohexylsulfenyl-5-dodecylsulfenyl[1,3,4]thiadiazole for single-crystal X-ray diffraction analysis could be isolated from a mixed solvent, namely ethanol and water in volume ratio of 9:1. Then, the influence of symmetry and cyclic or non-cyclic aliphatic substituents on the important structure parameters of the 2,5-bisalkylsulfenyl[1,3,4]thiadiazole derivatives were negligible, however, those structure characteristics were different for 5–cyclohexylsulfenyl–3H–[1,3,4]thiadiazole–2–thione, due to its thione structure. TGA/DTA study demonstrated the effect of the symmetry and van der Waals interaction on thermal stability, and the robust influence of the pseudo hydrogen bonding NH with C = S on the melting and crystallization phase transitions was revealed by DSC analysis. The pharmacokinetics, drug-likeness, medicinal chemistry friendliness, and toxicology of three derivatives of bis-alkylsulfenyl[1,3,4]thiadiazole were evaluated by two prediction tools of SwissADME and T.E.S.T tools predicted good pharmacokinetics, drug-likeness, and anti-toxicant properties in developmental toxicity for the bis-alkylsulfenyl[1,3,4]thiadiazoles and 5–cyclohexylsulfenyl–3H–[1,3,4]thiadiazole–2–thione. Finally, the in vitro antibacterial activity of two new 2-cyclohexylsulfenyl-5-cyclopentylsulfenyl[1,3,4]thiadiazole and 2-cyclohexylsulfenyl-5-dodecylsulfenyl[1,3,4]thiadiazole against S. aureus and E. coli, confirmed them as promising anti-bacterial agent. All obtained results proved that the physicochemical, thermal, pharmacokinetic, and biological properties of 2,5-bisalkylsulfenyl[1,3,4]thiadiazoles can be tuned by selecting appropriate substituents.

One‐Pot Synthesis of 2,4,6‐Trialkoxy‐ and Triaryloxybenzoates by Cs2CO3‐Mediated Tandem Dimerization/(3+3) Cyclocondensation of 1,3‐Acetonedicarboxylates

AbstractIn this study, Cs2CO3‐mediated one‐pot tandem dimerization/(3+3) cyclocondensation of 1,3‐acetonedicarboxylates followed by substitution of alkyl or aryl halides was developed to construct functionalized 2,4,6‐trialkoxy‐ and triaryloxybenzoates. In the effective reaction, the core benzene system was formed in a single‐step process under open‐vessel conditions. A plausible mechanism for this reaction is proposed and discussed herein.

Post-synthetic modification of Zr-based metal organic framework by schiff base zinc complex for catalytic applications in a click reaction

A novel nanocatalyst, denoted as UiO-66/Sal-ZnCl2, has been synthesized and systematically characterized employing a range of analytical techniques, including Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), Brunauer–Emmett–Teller (BET) surface area analysis, and inductively coupled plasma (ICP) analysis. The comprehensive analyses collectively affirm the effective coordination of zinc chloride onto the functionalized UiO-66. Subsequently, the catalytic efficacy of UiO-66/Sal-ZnCl2 was assessed in a one-pot, three-component click reaction involving terminal alkynes, alkyl halides, and sodium azide, conducted in an aqueous medium. The catalyst demonstrated remarkable catalytic activity, showcasing the capability to facilitate the reaction with high yields and exceptional regioselectivity. Noteworthy attributes of this nanocatalyst and the method include its elevated efficiency, recyclability, convenient product workup, and, significantly, the utilization of a sustainable solvent medium. The synthesis, characterization, and catalytic performance of this catalyst collectively contribute to its potential as an innovative and reusable nanocatalyst for diverse synthetic transformations.

Nickel‐Catalyzed α‐selective Hydroalkylation of Vinylarenes

AbstractC(sp3) centers adjacent to (hetero) aryl groups are widely present in physiologically active molecules. Metal‐hydride‐catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)−C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel‐hydride‐catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α‐selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand‐free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio‐ and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α‐branched alkylated pyrrole derivatives.

Microwave Assisted Williamson Synthesis: A Green Approach towards the Preparation of Ethers

Introduction: Microwave-assisted reactions align with the principles of green chemistry by significantly reducing synthesis time, avoiding high temperatures, and typically yielding high product quantities. Method: A catalyst was synthesized from waste banana peels, ensuring both availability and lowcost production. Ethers were synthesized using microwave irradiation at 300W, employing two different alkyl halide variants with both substituted and unsubstituted phenols. Results: The reaction proceeded efficiently without the need for corrosive bases such as caustic soda or caustic potash. Microwave irradiation facilitated reduced reaction times for ether formation. Additionally, the supported catalyst demonstrated the advantage of reusability. Conclusion: This protocol offers several benefits, including the use of a green solvent and the exclusion of phase transfer catalysts and harsh conditions. Consequently, an efficient and green synthesis of ethers has been achieved.