Alkylation Reactions Research Articles

Strategies for Using Quaternary Ammonium Salts as Alternative Reagents in Alkylations.

Alkylation reactions are pivotal in organic chemistry, with wide-ranging utilization across various fields of applied synthetic chemistry. However, conventional reagents employed in alkylations often pose substantial health and exposure risks. Quaternary ammonium salts (QAS) present a promising alternative for these transformations offering significantly reduced hazards as they are non-cancerogenic, non-mutagenic, non-flammable, and non-corrosive. Despite their potential, their use in direct organic transformations remains relatively unexplored. This review outlines strategies for utilizing QAS as alternative reagents in alkylation reactions, providing researchers with safer approaches to chemical synthesis.

Asymmetric synthesis of allylic sulfonamides with axially and central chirality via palladium-catalyzed of atroposelective N-allylic alkylation

Axially chiral anilide compounds are an emerging but scarcely investigated class of stereogenic molecules with potential applications as chiral catalysts, biologically active scaffolds and functional materials. Compared to the C–C axially chiral molecules, the synthesis of axially chiral anilide compounds is a challenge owing to the lower rotation barriers. Herein, the construction of chiral allylic amine bearing axial chirality and central chirality via Pd-catalyzed atroposelective N-allylic alkylation reaction of cyclic vinyl carbonates and sulfonamides is reported. A diverse range of chiral sulfonamides bearing axial chirality and central chirality were synthesized in high yields and excellent enantioselectivities (up to 92 ​% yield and 99 ​% ee). In addition, the practical application of this protocol was also demonstrated by gram-scale synthesis and derivatives of the compound.

A Mass Spectrometry Strategy for Protein Quantification Based on the Differential Alkylation of Cysteines Using Iodoacetamide and Acrylamide.

Mass spectrometry has become the most prominent yet evolving technology in quantitative proteomics. Today, a number of label-free and label-based approaches are available for the relative and absolute quantification of proteins and peptides. However, the label-based methods rely solely on the employment of stable isotopes, which are expensive and often limited in availability. Here we propose a label-based quantification strategy, where the mass difference is identified by the differential alkylation of cysteines using iodoacetamide and acrylamide. The alkylation reactions were performed under identical experimental conditions; therefore, the method can be easily integrated into standard proteomic workflows. Using high-resolution mass spectrometry, the feasibility of this approach was assessed with a set of tryptic peptides of human serum albumin. Several critical questions, such as the efficiency of labeling and the effect of the differential alkylation on the peptide retention and fragmentation, were addressed. The concentration of the quality control samples calculated against the calibration curves were within the ±20% acceptance range. It was also demonstrated that heavy labeled peptides exhibit a similar extraction recovery and matrix effect to light ones. Consequently, the approach presented here may be a viable and cost-effective alternative of stable isotope labeling strategies for the quantification of cysteine-containing proteins.

Quaternization of porphyrin conjugated organic polymer as an effective photocatalyst for fast degradation of 2,4-D and BPA

Conjugated organic polymers (COPs) originating from porphyrin and perylene bisimide exhibit promising capacity as photocatalysts benefiting from their inherent semiconducting characteristics, but most of them suffer from the hydrophobic properties, which strongly hinder their surface reactions and photocatalytic performance. To solve this problem, the quaternary ammonium groups were introduced into the porous skeleton of a COP-based photocatalyst (PDIN-Py) through Friedel-Crafts alkylation & Menschutkin reactions to yield a super-hydrophilic COP, denoted as PDIN-PyN+. Apart from the hydrophilicity, such post-modification strategy also enhances the visible light utilization, boosts the photogenerated carriers transport and endows PDIN-PyN+ with more positive zeta potential (21.9 mV), thus enhancing the electrostatic interaction with target anionic model pollutants including bisphenol A (BPA) and 2,4-dichlorophenoxyacetic acid (2,4-D) and improving the photocatalytic degradation performance. The removal efficiency (η) of PDIN-PyN+ towards 2,4-D (150 ppm) and BPA (20 ppm) can reach >99 % within 30 min under the irradiation of visible light, and the PDIN-PyN+ also exhibits excellent reusability and withstands various environmental influencing factors, thereby it shows great potential in real-water treatment scenarios.

Understanding the dewatering of fermentation-based 1,3-propanediol with acetone before cyclohexanone synthesis

Acetone can be produced by microbial fermentation using Clostridium acetobutylicum (acetone-n-butanol-ethanol fermentation, ABE fermentation), but it provides a mixture of acetone, 1-butanol, and ethanol. N-butanol and ethanol can be used as biofuels, but high-value applications of acetone generally require upgrading. Bio-based 1,3-propanediol is more readily produced by fermentation and separated at higher titers and has been used industrially. Therefore, the coupled upgrading of the two fermentation products can provide another avenue for high-value utilization of acetone. In this paper, salting-out extraction of 1,3-propanediol with acetone was carried out, and 1,3-propanediol and acetone would spontaneously form an organic phase, thus reducing the energy consumption in the 1,3-propanediol separation process. As the double alkylation reaction of acetone with equivalent 1,3-propanediol would generate cyclohexanone, the extraction of 1,3-propanediol with acetone can provide new insight into the process intensification (removing water, salt and water concentrated in the aqueous phase) for the 1,3-propanediol separation and conversion.

Recent Advances in the Nickel-Catalyzed Alkylation of C-H Bonds.

Functionalization of C-H bonds has emerged as a powerful strategy for converting inert, nonfunctional C-H bonds into their reactive counterparts. A wide range of C-H bond functionalization reactions has become possible by the catalysis of metals, typically from the second row of transition metals. First-row transition metals can also catalyze C-H functionalization, and they have the merits of greater earth-abundance, lower cost and better environmental friendliness in comparison to their second-row counterparts. C-H bond alkylation is a particularly important C-H functionalization reaction due to its chemical significance and its applications in natural product synthesis. This review covers Ni-catalyzed C-H bond alkylation reactions using alkyl halides and olefins as alkyl sources.

Stable 2-Azaallyl Salts as a Bridge between 2H-Azirines and Densely Functionalized 2H-Pyrroles.

An efficient protocol for the synthesis of stable 2-azaallyl anion salts by the reaction of alkyl 2-bromo-2H-azirine-2-carboxylates with trimethylsilyl cyanide/Bu4NF has been developed. The domino reaction proceeds in four steps via the cleavage of the azirine C-C bond to provide the tetrabutylammonium salts of stereochemically pure 2-azaallyl anions having U-configuration relative to the cyano groups. The anions with an ortho-substituted aryl group or styryl group exist as a mixture of two geometrical isomers across the N2-C3 bond. 2-Azaallyl anion salts have been shown to be convenient substrates for the one-pot synthesis of densely functionalized 2H-pyrroles by the alkylation-cyclization sequence.

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions.

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods for their functionalization require them to first be converted into a more activated derivative, while recent years have seen a vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can be used toward this goal. These transformations are broadly classified into three categories. Deoxygenative functionalizations, representing derivatization of the C-O bond, enable the alcohol to act as a leaving group toward the formation of new C-C bonds. Etherifications, characterized by derivatization of the O-H bond, represent classical reactivity that has been modernized to include mild reaction conditions, diverse reaction partners, and high selectivities. Lastly, chain functionalization reactions are described, wherein the alcohol group acts as a mediator in formal C-H functionalization reactions of the alkyl backbone. Each of these three classes of transformation will be discussed in context of intermolecular arylation, alkylation, and related reactions, illustrating how catalysis can enable alcohols to be directly harnessed for organic synthesis.

Fine-Tuning Electron-Donor Capability in the Basic Anion of Poly(ionic liquid) Frameworks for Revolutionizing Catalytic Synthesis of Ethyl Methyl Carbonate with Both Ultrahigh Catalytic Activity and Selectivity.

Ethyl methyl carbonate (EMC) is a crucial solvent extensively utilized in lithium-ion battery electrolytes; the transesterification of dimethyl carbonate (DMC) with ethanol is a pivotal reaction for EMC production. However, this reaction faces challenges due to the trade-off between catalytic activity and selectivity from the basic catalysts. In this issue, we report an innovative strategy through fine-tuning the electron-donor capability of the basic phenolate anion ([PhO]) in a novel poly(ionic liquid) (PIL) framework, as synthesized via an alkylation reaction between 1,3,5-tris(bromomethyl)benzene, biphenyldiimidazole, and N,N'-carbonyldiimidazole (CDI) to trigger targeted basicity that can directionally catalyze the transesterification of DMC with ethanol, so as to achieve both ultrahigh catalytic activity and selectivity toward EMC. By varying the substituent groups with electron-withdrawing and electron-donating effects on the phenolate anion, the PILs show expected changes in the catalytic performance, following well with the trend of charge density on these substituted phenolate anions. The optimized catalyst [CPIL-CDI][MeOPhO], induced by p-methoxyphenolate anions, allows an extraordinary EMC yield of 72.19% and an EMC selectivity of 91.48% under mild conditions without any process intensifications, suppressing all of the reported catalysts reported to date. Outcomes and approaches shown in this work have the potential to expedite the systematic design of cations and anions within PILs for industrial-scale EMC production through environmentally friendly transesterification processes.

Investigating the Role of Cs Species in the Toluene–Methanol Side Chain Alkylation Catalyzed by CsX Catalysts

The side chain alkylation of toluene with methanol was studied on a series of CsX catalysts prepared by varying the Cs species and ion exchange conditions. The effects of various parameters, such as the exchanging temperatures and times on the adsorption/activation properties of different CsX catalysts, were investigated by combining a variety of characterization means for understanding the role of Cs species in the side chain alkylation reaction. On the basis of the various characterization results and their related literature results, it can be proposed that the Cs ions located on the ion-exchanged sites of X zeolites could effectively adsorb and activate toluene molecularly through modifying the basicity of framework oxygen, whereas the cluster of cesium oxide (Cs2O) could ensure the effective conversion of methanol into formaldehyde. Additionally, Cs ions can promote the production of monodentate formate, which enhances the selectivity of styrene. However, too much Cs2O will lead to the excessive decomposition of methanol into CO2, CO, and H2, thus inhibiting the production of styrene. In summary, the presence of suitable amounts of Cs ions and Cs2O clusters plays a significant role in the formation of the side chain products of styrene and ethylbenzene.

N‐Heteroaromatic Fluoroalkylation through Ligand Coupling Reaction of Sulfones

AbstractLigand coupling on hypervalent main group elements has emerged as a pivotal methodology for the synthesis of functionalized N‐heteroaromatic compounds in recent years due to the avoidance of transition metals and the mildness of the reaction conditions. In this direction, the reaction of N‐heteroaryl sulfur(IV) and N‐heteroaryl phosphorus(V) compounds has been well studied. However, the ligand coupling of sulfur(VI) is still underdeveloped and the reaction of alkyl N‐heteroarylsulfones is still elusive, which does not match the high status of sulfones as the chemical chameleons in organic synthesis. Here we present a ligand coupling‐enabled formal SO2 extrusion of fluoroalkyl 2‐azaheteroarylsulfones under the promotion of Grignard reagents, which not only enriches the chemistry of sulfones, but also provides a novel and practical synthetic tool towards N‐heteroaromatic fluoroalkylation.

Nickel‐Catalyzed Intramolecular Dual Annulation Reaction of Alkyl Nitrile‐Containing 1,2,3‐Benzotriazin‐4(3H)‐ones: A Pathway to Access Diversely Polycyclic Quinazolinone Alkaloids

AbstractHerein, we report a nickel‐catalyzed intramolecular dual annulation reaction of alkyl nitrile‐containing 1,2,3‐benzotriazin‐4(3H)‐ones to synthesize polycyclic quinazolinones. This catalytic reaction can construct the core structure of polycyclic quinazolinone alkaloids; therefore, we also apply this reaction as the critical step to access fifteen relevant alkaloids to demonstrate efficacy.

Synthesis of 2-Substituted Indoles via Migration Reaction of 3-Substituted Indoles with Triflic Acid.

This study showcases the 1,2-migration reactions of alkyl and aryl groups on the indole molecule. Trifluoromethanesulfonic acid effectively facilitates the migration of the substituent from C3- to C2-position of the indole structure. The resulting C2-substituted indoles offer a valuable pathway for the synthesis of natural products and medicinal compounds.

Eco-Friendly Bamboo-Based Composites

The study focuses on obtaining bamboo-based composite materials and new environmentally friendly binders with different degrees of silylation (15-35%) at different pressures and temperatures. The synthesis was carried out using silylated polystyrene (poly[trimethoxy(4-vinylphenethyl)] silane) and styrene as a binder and reinforcing agent in the presence of organic/inorganic additives, antioxidants and antipirene. Poly[trimethoxy(4-vinylphenethyl)] silane, a solid brown substance, was synthesized via an alkylation reaction of vinyltrimethoxysilane and polystyrene, in the presence of anhydrous AlCl3. This paper presents the development of composites for ecological purposes (eco-composites) using bamboo fibers and their basic mechanical properties. The surface structures of the new composites were studied by several techniques including electron microscopy, energy dispersive X-ray microanalysis, bending test, Charpy impact test, thermogravimetry study, and water absorption determination. The new composites are characterized by good mechanical properties, thermal resistance, ecological purity, and water absorption capacity much smaller than the water absorption of existing particle boards.

Acidic ionic liquid-based liposome for efficient catalytic degradation of azo dyes

Amphiphilic ionic liquids (ILs) with an imidazole head and two undecene tails (abbreviated as [MimV11, V11]Br) were synthesized through alkylation reaction. They were utilized as lipoid monomers for constructing an isotropic catalytic degradation platform of azo dyes. The spherical structure of this IL-based liposome was reinforced by cross-linking polymerization of the olefin tails. The imidazole groups served as anchor points for attaching catalytic heteropolyanions (such as [PW12O40]3-, [PMo12O40]3-) to the liposomal vehicle. Furthermore, the arrangement of these linkers on the liposome surface facilitated the trapping and enrichment of the catalytic species. Consequently, a series of isotropic catalysts decorated with heteropolyanions (poly[MimA11, A11][heteropolyanions]) were prepared through anion exchange, where sufficiently exposed heteropolyanions maximized the catalytic degradation activity. The morphology, structure, and properties of the catalysts were confirmed using SEM, TEM, FTIR, XPS, UV–vis, and GC–MS. Experimental results found that poly[MimA11, A11][PW12O40] was the optimal catalyst, achieving a removal efficiency of 97.2% for methyl orange (MO) within 3 h. The intermediates involved in the reaction were analyzed to propose the degradation pathway of MO. Moreover, this kind of solid catalyst could be recovered by centrifugation, and its degradation efficiency remained above 91% even after five cycles. This research provides valuable insights for expanding the applications of IL-functionalized materials.

Insight studies on the deactivation of sulfuric acid regeneration catalyst

The SAR unit is used for regenerating spent sulfuric acid for alkylation reactions. In the SAR unit, the converter employs a potassium and vanadium-based catalyst for conversion of SO2 to SO3. The multiple bed fixed bed reactor is there to ensure that almost entire amount of SO2 is converted to SO3. On observing the generation of large amounts of fines in the reactor catalyst, the spent catalyst and fines are collected for insight studies. The current study enlightens the possible causes of catalyst deactivation and fines generation. Structural changes in potassium/vanadium based catalyst during the oxidation of sulfur dioxide identified as the major cause of catalyst deactivation. Such structural changes and their impact on catalyst property were determined using various physico-chemical characterization methods like crushing strength, Loss on drying (LOD), XRF, XRD, FTIR and XPS analysis. LOD analysis shows the higher moisture and volatile content in spent and fines compared to fresh catalyst. High moisture content in spent catalyst decreases hardness of catalyst resulting in leaching of vanadium salt and carrier degradation due to thermal cycling. Chemical analysis data found to show the active vanadium content in fines is higher compared to spent which indicates vanadium has leached out from fresh catalyst and is deposited on fines. These observations are further correlated with XRD and XPS results. XPS analysis shows the relative distribution of V4+ and V5+ species on the catalyst surface are altered and found very low concentration of V4+ sites on spent catalyst. The XRD analysis demonstrates the leaching of the active component, potassium vanadyl sulfate K(VO2) (SO4)·3H2O, which then accumulated in the fines fraction. FT-IR and XRD results further shows increase in sulfate accumulation on spent catalyst surface along with phase changes. FTIR analysis of simulated spent catalyst are well correlated with these findings.

Zr/Hf-containing metallocene-based ceramic precursors

Polymer-derived-ceramic (PDC) route is an excellent strategy to tailor components at the molecular level, while existing synthetic methods face various problems such as complex preparation, multi-step reaction, and high conversion temperature, etc. Here, we propose an approach to prepare Zr-, Hf-, or Zr/Hf-containing metallocene-based ceramic precursors, which are constructed by the alkylation reaction between cyclopentadienyl ligand and methylene. Through the homogeneous and one-pot reaction occurs, we collect the target products. The reaction condition is mild, and the conversion temperature (1400 °C) is relatively low, and with a high ceramic yield (57.50–66.34%). The obtained metal-containing polymers are further converted to the orthorhombic phase (M7O8.79F9.71, M = Zr, Hf) after pyrolysis at 800 °C. Annealing at an intermediate temperature of 1400 °C in an argon atmosphere results in cubic crystalline ZrC or HfC nanoparticles embedded in a ceramic matrix. The free carbons are in-situ formed after high-temperature treatment, and higher disorder of carbons is observed with increasing temperature. This work provides a good strategy for the potential precursor of ultrahigh-temperature ceramics.

Mechanism and kinetics of catalytic decalin alkylation for the synthesis of high-performance fuel

Alkyl decalins are promising jet fuel components with high density and well cryogenic properties, but are difficult to obtain. Here we bring up a facile approach to synthesize methyl-substituted decalins including methyl decalin, dimethyl decalin and trimethyl decalin via catalytic alkylation reaction. The reaction conditions are optimized to obtain the high decalin conversion of 83.1 %. Based on a series of experiments, it is indicated that the intermediate complex formed by tetramethylsilane, aluminum chloride and dichloroethane is the key to accelerate the reaction rate, and the reaction mechanism is proposed. Moreover, a pseudo-first-order irreversible reaction dynamics is studied, and the reaction kinetics parameters and reaction rate equati andons are obtained. After vacuum distillation, the fuel product shows high density (0.872 g/cm3) and high volumetric neat heat of combustion (36.9 MJ/L), much higher than those of RP-3 fuel. This work provides a facile method to synthesize high-performance jet fuel.

Colorimetric detection of Staphylococcus aureus based on self-linkable and hollow organic-inorganic nanocomposites as light-driven oxidase-like nanozyme for cascade signal amplification

Facing increasingly serious bacterial infections and their threat to food safety and human health, exploring specific and sensitive bacterial strategies is indispensable. Nanozyme-based colorimetric biosensors with the superiorities of easy-to-read and catalytic signal amplification have attracted increasing interest. However, few investigations relate to the nanozymes with excellent light-driven oxidase-like activity. In this study, a sensitive colorimetric biosensor for Staphylococcus aureus (S. aureus) detection was constructed based on a light-driven oxidase-like nanozyme (PHCS@CuNcPOPTP) as well as the self-chain linking process. The hollow organic-inorganic nanocomposite (PHCS@CuNcPOPTP) was prepared by a one-step Friedel-Crafts alkylation reaction. The PHCS@CuNcPOPTP exhibited excellent and synergistically enhanced light-driven oxidase-like activity originating from its unique photosensitive properties. Subsequently, PHCS@CuNcPOPTP was served as a scaffold, loading with the rabbit anti-Staphylococcus aureus Rosenbach tropina antibody (bs-4582R, Ab2), DNA1, and DNA2, respectively, to construct signal probes (PHCS@CuNcPOPTP@Au-Ab2/DNA1, PHCS@CuNcPOPTP@Au-DNA1, and PHCS@CuNcPOPTP@Au-DNA2). By the repetitive DNA hybridization among signal probes, a large amount of PHCS@CuNcPOPTP-DNA dendrimers were formed and utilized to trigger the chromogenic reaction without the participation of high-concentration H2O2, resulting in the cascaded catalytic amplification and the lower background signal. As expected, the suggested sensing platform presented ultrasensitive bacterial detection with a remarkably broad linear range (101 to 108 CFU/mL) and a limit of detection (LOD, 3.40 CFU/mL).

From Pulp to Aromatic Products-Reaction Pathways of Lignin Depolymerization.

This study investigated the depolymerization of lignin into aromatic monomer compounds under hydrothermal conditions. A reaction scheme highlighting secondary alkylation reactions as well as the molecular weight shift was developed based on the experimental data. Lignin is produced in large quantities in paper production and dissolved in what is known as black liquor (BL). To avoid lignin recovery as an additional process step, BL is used directly as feedstock in the hydrothermal liquefaction (HTL) in this work. We performed various batch experiments in micro autoclaves with BL and model substances at different reaction temperatures (TR = 250-400 °C) and a holdingtime of tR = 20 min, as well as continuous experiments (TR = 325-375 °C, tR = 20 min). We were able to show that different derivatives of catechols are the main products among the monomers in our process. With the help of the model substance experiments, we were able to work out three main reactions: demethoxylation, demethylation, and alkylation. This behavior could be observed in the case of BL from hardwood as well as from softwood. 31P nuclear magnetic resonance (NMR) spectroscopy analysis has shown that these reactions take place on aromatic monomers as well as on larger aromatic oligomer structures. At higher temperatures, a large fraction of the carbon ends up in the solid product, while the yields of the monomers decrease sharply. 13C NMR spectroscopy of the solid material shows that the monomers are probably incorporated into the solid phase by repolymerization. We were also able to see this effect using size exclusion chromatography analysis based on the relative molecular weight. From all of the analytical results of the products, a reaction scheme was developed that describes the reaction pathways of the lignin during HTL. Based on this, a reaction kinetic model can be developed in the next step.