Alkyl Halides Research Articles

Photoinduced copper-catalyzed asymmetric cyanoalkylalkynylation of alkenes, terminal alkynes, and oximes.

The asymmetric dicarbofunctionalization of alkenes via a radical relay process can provide routes to diverse hydrocarbon derivatives. Three-component carboalkynylation, limited to particular alkyl halides and using readily available cycloketone oxime esters as redox-active precursors, is restricted by the available pool of suitable chiral ligands for broadening the redox potential window of copper complexes and simultaneously creating the enantiocontrol environment. Herein, we report a new hybrid tridentate ligand bearing a guanidine-amide-pyridine unit for photoinduced copper-catalyzed cyanoalkylalkynylation of alkenes. Leveraging the copper catalyst's redox capability is achieved via merging the electron-rich ligand with a readily organized configuration and enhanced absorption in the visible light range, which also facilitates the enantioselectivity. The generality of the catalyst system is exemplified by the efficacy across a number of alkenes, terminal alkynes and cycloketone oxime esters, working smoothly to give alkyne-bearing nitriles with good yields and excellent enantioselectivity. A mechanistic study reveals that the chiral copper catalyst meets the requirements of possessing sufficient reduction ability, good light absorption properties, and appropriate steric hindrance.

Iodine(iii)-mediated oxidative chlorination, bromination and iodination of chromone derivatives using alkyl halides as the solvent and halogen source

A protocol for iodine(iii)-mediated oxidative chlorination, bromination and iodination of chromone derivatives has been developed using alkyl halide solvents such as CHCl3, CH2Br2 and CH2I2 as the halogen source.

Electrochemically driven cross-electrophile esterification of alkyl halides

A catalyst-free electrochemically driven cross-electrophile esterification has been developed. Various 2-phenylacetic esters are accessed from simple and cheap alkyl halides and alkyl chloroformates with up to 98% yields.

A silylboronate-mediated strategy for cross-coupling of alkyl fluorides with aryl alkanes: mechanistic insights and scope expansion.

The construction of C(sp3)-C(sp3) bonds is pivotal in organic synthesis; however, traditional methods involving alkyl halides are often limited by substrate tolerance and bond dissociation energies, particularly with alkyl fluorides. Herein, we report a silylboronate-mediated cross-coupling strategy that circumvents these challenges, enabling the efficient formation of C(sp3)-C(sp3) bonds between alkyl fluorides and aryl alkanes under mild conditions. Various alkyl fluorides have also been effectively utilized, demonstrating the versatility and broad applicability of this approach. The use of diglyme is critical for this transformation which encapsulates potassium cations and enhances the reaction efficiency. Conventional alkyl halides, including chlorides, bromides, and iodides, are also suitable for this transformation. Density functional theory (DFT) calculations were conducted on the silylboronate-mediated coupling reactions for the first time. Interestingly, while experimental results suggest a radical mechanism, DFT calculations indicate a preference for an ionic pathway.

An extended-gate-type organic transistor for monitoring the Menschutkin reaction of tetrazole at a solid-liquid interface.

We herein propose an approach to visualize the Menschutkin reaction at an interface between a self-assembled monolayer with nucleophilic properties and water containing alkyl halides. An organic field-effect transistor functionalized with a nucleophilic monolayer has detected in situ alkylation depending on differences in the leaving group ability and the bulkiness of electrophilic alkyls.

Alcohol synthesis based on the SN2 reactions of alkyl halides with the squarate dianion.

A convenient method has been developed for transforming alkyl halides into the corresponding alcohols via an SN2 reaction. Treatment of an alkyl halide with the squarate dianion at high temperature produces mono-alkyl squarate, and a one-pot basic hydrolysis of the intermediate affords the alcohol in good yield.

Access to disulfides through ligand-controlled nickel-catalyzed dithiosulfonate and alkyl halides

Nickel-catalyzed C–SS reductive cross-coupling reaction of dithiosulfonate and unactivated alkyl halides for producing unsymmetric disulfides with broad substrate scope under mild conditions and with excellent functional group tolerance.

Extraction and Characterization of Bioactive Compounds from Plant, Michelia champaca (L) in Polar Solvents: GC- MS and Antibacterial properties

For thousands of years, medicinal plants were used to cure many common infectious diseases and health issues. An extremely important medicinal plant called Michelia champaca L.(Magnoliaceae) has long been used to treat various ailments, including inflammatory ones. The current study was designated to explore the antibacterial properties of the alcoholic and methanolic extract of Magnolia champaca leaves and its different fractions. Antibacterial activity was evaluated against a panel of gram-positive (Staphylococcus aureus, Enterococcus faecalis, Staphylococcus saprophyticus) and gram-negative (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Acinetobacter baumannii, and Salmonella paratyphi) bacterial strains using the disc diffusion method. According to the results, methanolic extract showed slightly higher antibacterial activity than acetone extract. The highest zone of inhibition in the methanolic extract was Staphylococcus aureus followed by Staphylococcus saprophyticus and Proteus mirabilis. The acetone extract shows significant efficiency in gram-positive strains such as Staphylococcus spp. The FTIR spectroscopic studies revealed the presence of various functional compounds such as alkanes, carboxylic acid, aromatic compounds, esters, amines, nitro, alkyl halide, and phenols. Acetone and methanol extracts showed the presence of halo compounds, anhydride, isothiocyanate, alcohol, and phenol. GCMS analysis of both extracts shares five biocomponents: Alpha copaene, beta-elemene, beta-caryophyllene, and phytol showed antibacterial activity. This investigation showed that M. champaca leaf extracts had prospective therapeutic properties in terms of their antibacterial properties.

Phytochemical Analysis and hypoglycemic potential of Filago hurdwarica (Wall. ex DC.) Wagenitz in alloxan induced diabetic mice.

Plants have profound therapeutic benefits, more economical treatments, fewer side effects, and a relatively cheap cost, making them a source of drugs for protective, preventative, curative, or conducive purposes and creating novel phytomedicines. Plant derived medicines are relatively safe compared to synthetic medicines. Many plants have proved to successfully aid in the treatment of diabetes including Filago hurdwarica (Wall. ex DC.) Wagenitz. The current investigations were therefore designed to assess the phytochemical, antioxidant, antidiabetic, and antihyperlipidemic activities of F. hurdwarica. The phytochemical investigations and antioxidant activities of different extracts were carried out using standard chemical tests, DPPH, and H2O2 scavenging assays. F. hurdwarica plant extract in Hydromethanolic solution were prepared by Soxhletation method and stored in refrigerator at 4°C for two days before use. Swiss Albino mice were made diabetic by a single dose of alloxan (150 mg/kg). Hydromethanolic plant extract and fractions of F. hurdwarica were screened for antidiabetic activity and given to the alloxan-induced diabetic mice at a concentration of 150-250 mg/kg of body weight in different groups of 6 diabetic mice each orally once a day for 15 days. Glibenclamide is also given to another group to as a standard drug to support the result at a dose of 10 mg/kg of body weight orally once a day for 15 days. Blood glucose levels and body weights of mice were measured on 0, 4, 7, 11 and 15th days. The study found that the extract was safe up to the dose level of 2000 mg/kg and the dose response effect of chloroform extract (150-250 mg/kg) of F. hurdwarica showed expressive antihyperglycemic effects and also improved other altered biochemical parameters associated with diabetes. The FTIR and XRD spectra demonstrated the occurrence of phenols, alcohols, alkenes, alkyl halides, ketones, and aromatic compounds and confirmed the amorphous nature of the extract. GC-MS spectral analysis showed the tentative presence of 31 phytochemical constituents in the chloroform extract of F. hurdwarica with different retention time. To conclude, the chloroform extract (250 mg/kg) of F. hurdwarica revealed considerable antioxidant, antihyperglycemic, and antihyperlipidemic potential and is safe for treating diabetes and related complications.

Benzylamine promoted direct C–H arylation of arenes and heteroarenes via excitation with heat or light†

The carbon-halogen bond cleavage in aryl halides by single electron transfer (SET) is the crucial step in radical-based cross-coupling reactions. Accomplishing such cleavage using an organic system without the assistance...

Mechanochemical reduction of alkyl and aryl halides using mesoporous zinc oxide.

In this study, we propose a mechanochemical approach that combines mesoporous ZnO (m-ZnO) as a mechanoredox catalyst and silane-mediated atom transfer chemistry to achieve efficient hydrodehalogenation of organic halides. The reaction can be conducted under mild conditions without the use of a large amount of organic solvent. Substrates ranging from activated alkyl halides to unactivated aryl halides were converted to the corresponding debrominated hydrogenation products in moderate to excellent isolated yields (50-95%). In addition, m-ZnO can be recycled and reused without appreciable loss of catalytic activity.

Selective synthesis of an elusive C-functional bis-cyclam and study of its inhibition of the CXCR4 chemokine receptor.

This article presents the controlled synthesis of a rare example of C,C'-linked bis-cyclam architecture in mild conditions through the "bis-aminal" route previously used for the advantageous synthesis of cyclam, N- and C-functional cyclams and N,N'-bis-cyclams. Two synthetic pathways were explored with the smart design of α,β-unsaturated ketones or alkyl halides bis-cyclizing agents. The first led to the isolation of a key intermediate for the future design of N-functionalized bis-cyclams, whereas the second allowed the preparation of the targeted C,C'-xylylene-bis-cyclam under mild conditions with decent yield. This compound was then studied as a CXCR4 receptor inhibitor, one of the main applications known for bis-macrocyclic compounds, in particular in the context of HIV (human immunodeficiency virus) infection. Although results demonstrated that its potency is lower (i.e. 137-fold higher IC50) than the gold standard AMD3100 against HIV infection, clear evidence of CXCR4 inhibition is presented, confirming the potential of this novel architecture and related compounds in this research field.

Boryl radical-mediated halogen-atom transfer (XAT) enables the Sonogashira-like alkynylation of alkyl halides.

Alkynes are a crucial class of materials with application across the wide range of chemical disciplines. The alkynylation of alkyl halides presents an ideal strategy for assembling these materials. Current methods rely on the intrinsic electrophilic nature of alkyl halides to couple with nucleophilic acetylenic systems, but these methods faces limitations in terms of applicability and generality. Herein, we introduce a different approach to alkynylation of alkyl halides that proceeds via radical intermediates and uses alkynyl sulfones as coupling partners. This strategy exploits the ability of amine-ligated boryl radicals to activate alkyl iodides and bromides through halogen-atom transfer (XAT). The resulting radicals then undergo a cascade of α-addition and β-fragmentation with the sulfone reagent, leading to the construction of C(sp3)-C(sp) bonds. The generality of the methodology has been demonstrated by its successful application in the alkynylation of complex and high-value molecules.

Selective nickel-catalyzed disulfuration of alkyl halides with di/trithiosulfonates

Selective reductive disulfuration of alkyl halides with di/trithiosulfonate reagents was developed through ligand regulation, with key features of broad substrate scope, good tolerance and excellent selectivity to disulfides over trisulfides.

Gas-phase synthesis of [OU-X]+ (X = Cl, Br and I) from a UO22+ precursor using ion-molecule reactions and an [OUCH]+ intermediate.

Difficulty in the preparation of gas-phase ions that include U in middle oxidation states(III,IV) have hampered efforts to investigate intrinsic structure, bonding and reactivity of model species. Our group has used preparative tandem mass spectrometry (PTMS) to synthesize a gas-phase U-methylidyne species, [OUCH]+, by elimination of CO from [UO2(CCH)]+ [M. J. van Stipdonk, I. J. Tatosian, A. C. Iacovino, A. R. Bubas, L. Metzler, M. C. Sherman and A. Somogyi, J. Am. Soc. Mass Spectrom., 2019, 30, 796-805], which has been used as an intermediate to create products such as [OUN]+ and [OUS]+ by ion-molecule reactions. Here, we investigated the reactions of [OUCH]+ with a range of alkyl halides to determine whether the methylidyne is a also a useful intermediate for production and study of the oxy-halide ions [OUX]+, where X = Cl, Br and I, formally U(IV) species for which intrinsic reactivity data is relatively scarce. Our experiments demonstrate that [OUX]+ is the dominant product ion generated by reaction [OUCH]+ with neutral regents such as CH3Cl, CH3CH2Br and CH2CHCH2I.

Arbuzov meets 1,2-oxaphosphetanes: transient 1,2-oxaphosphetan-2-iums as an entry point to beta-halo phosphane oxides and P-containing oligomers.

Herein, we describe the synthesis of a 1,2σ3λ3-oxaphosphetane from ethylene oxide and its reactions with alkyl halides to form β-halo phosphane oxides in an Arbuzov-type reaction. When methyl triflate was used as a hard electrophile, cationic oligomerisation of 1,2-oxaphosphetanes was observed. DFT calculations indicate 1,2-oxaphosphetan-2-iums as intermediates and reveal differences between the Arbuzov and the potential Perkow reaction pathway.

High-throughput selection of (new) enzymes: phage display-mediated isolation of alkyl halide hydrolases from a library of active-site mutated epoxide hydrolases.

Epoxide hydrolase StEH1, from potato, is similar in overall structural fold and catalytic mechanism to haloalkane dehalogenase DhlA from Xanthobacter autotrophicus. StEH1 displays low (promiscuous) hydrolytic activity with (2-chloro)- and (2-bromo)ethanebenzene producing 2-phenylethanol. To investigate possibilities to amplify these very low dehalogenase activities, StEH1 was subjected to targeted randomized mutagenesis at five active-site amino acid residues and the resulting protein library was challenged for reactivity towards a bait chloride substrate. Enzymes catalyzing the first half-reaction of a hydrolytic cycle were isolated following monovalent phage display of the mutated proteins. Several StEH1 derived enzymes were identified with enhanced dehalogenase activities.

Visible-light-induced alkyl-arylation of olefins via a halogen-atom transfer process.

Visible-light-induced three-component 1,2-alkyl-arylation of alkenes and alkyl radical addition/cyclization of acrylamides have been realized via a photocatalytic halogen-atom transfer (XAT) process. This metal-free protocol utilizes readily available tertiary alkylamine as both an electron donor and an XAT reagent for the activation of alkyl halides using naphthalimide (NI)-based organic photocatalysts. This process features broad substrate scope and good functional group tolerance under mild conditions, and could be effectively applied to a variety of medicinally relevant substrates.

INVESTIGATION OF FUNGICIDAL PROPERTIES OF HEXYL BROMIDE COMPLEX OF N'-(2,2-BITCYCLO[2.2.1]HEPT-5-EN-2-YL-4,5-DIHYDRO-1-H-IMIDAZOLIN-1- YLETHYL)ETHANE-1,2-DIAMINE AS ANTIMICROBIAL ADDITIVE TO LUBRICANTCOOLANT FLUIDS

The results of a study of the antifungal properties of an imidazoline hexyl bromide complex obtained on the basis of bicyclo[2.2.1]hept-5-ene-2-carboxylic acid and triethylenetetraamine as an additive to cutting fluids are presented. First, imidazoline was obtained by reacting norbornene carboxylic acid with triethylene tetraamine. In the next step, imidazoline was reacted with hexyl bromide to obtain its alkyl halide complex. The physicochemical properties of the resulting complex were determined, and its composition and structure were confirmed by IR spectroscopy. The complex has been tested as an antimicrobial additive in cutting fluids. It was found that the resulting complex has a destruction zone of 1.3-1.5 cm at a concentration of 0.25% and 2.4-2.6 cm at a concentration of 0.5%. N'-(2,2-bicyclo[2.2.1]hept-5-en-2-yl-4,5-dihydro-1-Himidazolin-1-ylethyl)ethane-1,2-diamine hexyl bromide complex as an antimicrobial additive exhibiting high fungicidal properties, destroys fungi even at a concentration of 0.25% - the affected area is 1.3-1.5 cm.

Enantioselective organocatalyzed one-pot synthesis of N-phenyl thioether-tethered tetrasubstituted dihydropyrrole-3-carbaldehydes.

An efficient method for the asymmetric one-pot synthesis of N-phenyl thioether-tethered tetrasubstituted chiral 4,5-dihydropyrrole-3-carbaldehydes have been developed using readily available benzothiazolium salts and α,β-unsaturated aldehydes as starting materials in the presence of the chiral organocatalyst (R)-diphenylprolinol trimethylsilyl ether. The protocol afforded various functionally enantioenriched chiral tetrasubstituted 4,5-dihydropyrrole-3-carbaldehydes in high yields, with excellent enantio- and diastereoselectivity (≤90% yield, ≤98% ee, and >20 : 1 d.r.). This asymmetric one-pot reaction starts with the reaction of azomethine ylides with dipolarophiles to yield pyrrolo-thiazine-2-carbaldehydes as intermediates. Subsequently, the electrophile alkyl halide is attacked by the sulfur atom of the intermediate, followed by C-S bond cleavage (ring-opening), which furnishes the desired chiral tetrasubstituted 4,5-dihydropyrroles.