Alkylation Reactions Research Articles

Synthesis of Fluorene Derivatives Via TfOH-catalyzed Intramolecular Friedel-Crafts Alkylation Reactions

Synthesis of Fluorene Derivatives Via TfOH-catalyzed Intramolecular Friedel-Crafts Alkylation Reactions

Surface-Modified Nano-Hydroxyapatite Uniformly Dispersed on High-Porous GelMA Scaffold Surfaces for Enhanced Osteochondral Regeneration.

This study aims to investigate the impact of enhancing subchondral bone repair on the efficacy of articular cartilage restoration, thereby achieving improved osteochondral regeneration outcomes. In this study, we modified the surface of nano-hydroxyapatite (n-HAp) through alkylation reactions to prepare n-HApMA. Characterization techniques, including X-ray diffraction, infrared spectroscopy scanning, thermogravimetric analysis, particle size analysis, and electron microscopy, were employed to analyze n-HApMA. Bioinks were prepared using n-HApMA, high porosity GelMA hydrogel, and adipose tissue derived stromal cells (ADSCs). The rheological properties of the bioinks during photocuring were investigated using a rheometer. Based on these bioinks, a biphasic scaffold was constructed. The viability of cells within the scaffold was observed using live-dead cell staining, while the internal morphology was examined using scanning electron microscopy. The stiffness of the scaffold was evaluated through compression testing. Scaffolds were implanted into the osteochondral defects of New Zealand rabbit knees, and microCT was utilized to observe the subchondral bone repair. Hematoxylin and eosin (H&E) staining, Masson's trichrome staining, and Safranin O/Fast Green staining were performed to assess the regeneration of subchondral bone and cartilage. Furthermore, immunohistochemical staining was employed to detect the expression of osteogenic and chondrogenic-related molecules. Scaffold characterization revealed that surface modification enables the uniform distribution of n-HApMA within the GelMA matrix. The incorporation of 5% n-HApMA notably enhanced the elastic modulus and stiffness of the 6% high-porosity GelMA in comparison to n-HAp. Moreover, in-vivo study showed that the homogeneous dispersion of n-HApMA on the GelMA matrix facilitated the osteogenic differentiation of adipose-derived stem cells (ADSCs) and promoted osteochondral tissue regeneration. These findings suggest potential applications of the n-HApMA/GelMA composite in the field of tissue engineering and regenerative medicine.

Исследования катализатора алкилирования Purolite СТ151DRY фирмы Purolite в реакции алкилирования фенола олигомеров этилена фракции С16–С18

The possibility of using a Purolite alkylation catalyst of the CT151DRY brand in the reaction of alkylation of phenol with ethylene oligomers of the C16-C18 fraction to obtain the target alkylphenol, which is a semi-product in the production of multifunctional additives to lubricants is considered in the article. It is shown that the Purolite CT151DRY catalyst is resistant to mechanical influences and high temperatures within the studied range up to 180 °C and the synthesis duration up to 50 hours while maintaining a high alkylating ability in the reaction of phenol alkylation by ethylene oligomers of the C16-C18 fraction and is highly sensitive to changes in the composition of raw materials and the change of raw ethylene oligomers. The Purolite CT151DRY catalyst has an alkylating ability comparable to other catalysts and can be recommended to obtain the target alkylphenol.

Enantioselective Rh(I)-Catalyzed C-H Arylation of Ferroceneformaldehydes.

As an important class of platform molecules, planar chiral ferrocene carbonyl compounds could be transformed into various functional groups offering facile synthesis of chiral ligands and catalysts. However, developing efficient and straightforward methods for accessing enantiopure planar chiral ferrocene carbonyl compounds, especially ferroceneformaldehydes, remains highly challenging. Herein, we report a rhodium(I)/phosphoramidite-catalyzed enantioselective C-H bond arylation of ferroceneformaldehydes. Readily available aryl halides such as aryl iodides, aryl bromides, and even aryl chlorides are suitable coupling partners in this transformation, leading to a series of planar chiral ferroceneformaldehydes in good yields and excellent enantioselectivity (up to 83% yield and >99% ee). The aldehyde group could be transformed into diverse functional groups smoothly, and enantiopure Ugi's amine and PPFA analogues could be synthesized efficiently. The latter was found to be a highly efficient ligand in Pd-catalyzed asymmetric allylic alkylation reactions. Mechanistic experiments supported the formation of imine intermediates as the key step during the reaction.

Design and Synthesis of Rigid‐Featured Tertiary Amine‐Derived C2‐Symmetric Chiral Furan‐N,N′‐dioxide Ligands

AbstractTo expand the chemical space of chiral N‐oxides and chiral furan‐containing ligands, herein we designed and synthesized a new class of rigid‐featured tertiary amine‐derived C2‐symmetric chiral furan‐N,N′‐dioxide (Fu‐2NO) ligands from optically pure l‐prolinamides/hydroxylprolinamides in operationally simple two steps and up to 57 % overall yield. The newly developed rigid‐featured chiral Fu‐2NO ligands possesses two pyrroloimidazolone‐based N‐oxides as non‐flat chiral walls, and afforded the opportunity for fine‐tuning the ligand electronic and conformational properties by judicious choice of the substituent in the nonligating nitrogen atom. More importantly, The Fu‐2NO ligands can tolerate air and moisture such that no special handling is needed for their storage, and can be applied in the Ni(II)‐catalyzed asymmetric Friedel‐Crafts alkylation reaction of indole.

Detoxification of coal-tar pitch by alkylation method and toxicity evaluation by chemical index, fumes and water-soluble substances

Coal-tar pitch (CTP) output in China has consistently exceeded 7 million tons annually since 2011. CTP contains 16 toxic polycyclic aromatic hydrocarbons (PAHs) that are preferentially monitored by the American Environmental Protection Agency (EPA). As a result, the widespread and extensive use of CTP is restricted. Consequently, finding ways to reduce the toxicity of CTP has become an urgent concern. In the paper, the reaction conditions were optimized using model compounds (naphthalene, fluorene, anthracene, phenanthrene, fluoranthene, pyrene, benzo [a]pyrene) of CTP. Subsequently, the CTP was modified through alkylation reaction using 1-dodecene, and the detoxification effect was evaluated based on chemical index, fumes, and water-soluble substances. The total content of 16 toxic PAHs in the modified CTP (MCTP) decreased by 75.56% compared to the original CTP. The toxicity equivalent quotient (TEQ) of the MCTP was reduced by more than 65% according to different environmental standards. The content of the 16 PAHs detected in MCTP fumes released at 140 °C decreased by 80.89%, while in water-soluble substances it decreased by 64.04% and 76.67% at 30 °C and 60 °C, respectively. These results strongly indicate the effectiveness of the alkylation method in reducing the toxicity of CTP. However, in order to develop more environmentally-friendly materials, it is necessary to explore more efficient catalysts and cheaper modifiers, which will be the focus of our future research. Novelty StatementThis study investigated the toxicity inhibition of CTP to reduce the content of PAHs by alkylation method. The modification process was analyzed using model compounds to understand the potential reaction pathways. The objective of toxicity inhibition was achieved by creating low-toxicity and long-chain alkyl substitutes. Additionally, the toxicity of CTP and MCTP was assessed by introducing fumes and water-soluble substances.

Asymmetric Hydrogenation of Tetrapyridine‐Type N‐Heteroarenes Using Phosphine‐Free Ruthenium Diamine Catalysts†

Comprehensive SummaryChiral ruthenium‐catalyzed enantioselective hydrogenation of tetrapyridine‐type N‐heteroarenes was firstly developed. The partial reduction of adjacent tetraheteroaromatic substrates proceeded smoothly in the presence of phosphine‐free chiral cationic ruthenium diamine complexes, affording unprecedented high reactivity, enantioselecitivity and diastereoselectivity (up to 93% yield, >99% ee and 92 : 8 dr). The potential application of chiral tetradentate pyridine‐amine products as chiral ligands has been demonstrated in the Cu‐catalyzed asymmetric Friedel–Crafts alkylation reaction between indoles and nitroalkenes.

A Theoretical Kinetic Study on Concerted Elimination Reaction Class of Peroxyl-hydroperoxyl-alkyl Radicals (•OOQOOH) in Normal-alkyl Cyclohexanes.

The concerted elimination reaction class of peroxyl-hydroperoxyl alkyl radicals (•OOQOOH) plays a crucial role in the low-temperature combustion of normal-alkyl cyclohexanes. The generation of the relatively unreactive HO2 radicals in this reaction is one of the factors leading to the negative temperature coefficient (NTC) behavior, which hinders the low-temperature oxidation of normal-alkyl cyclohexanes. In this study, 44 reactions are selected and divided into 4 different subclasses according to the nature of the carbon atom where the H atom is eliminated and the reaction center position. Utilizing the CBS-QB3 method, we compute the energy barriers for the concerted elimination reactions of peroxyl-hydroperoxyl alkyl radicals. Following this, we assess both the high-pressure limit and pressure-dependent rate constants for all reactions by applying TST and RRKM/ME theory. These calculations allow for the development of rate rules, which come to fruition through an averaging process involving the rate constants of representative reactions within each subclass. Our work provides accurate rate constants and rate rules for this reaction class, which can aid in constructing more accurate combustion mechanisms for normal-alkyl cyclohexanes.

Ruthenium-Catalyzed Selective α-Alkylation of β-Naphthols using Primary Alcohols: Elucidating the Influence of Base and Water.

Functionalized arenes and arenols have diverse applications in chemical synthesis and material chemistry. Selective functionalization of arenols is a topic of prime interest. In particular, direct alkylation of arenols using alcohols is a challenging task. In this report, a ruthenium pincer catalyzed direct α-alkylation of β-naphthol using primary alcohols as alkylating reagents is reported. Notably, aryl and heteroaryl methanols and linear and branched aliphatic alcohols underwent selective alkylation reactions, in which water is the only byproduct. Notably, catalytically derived α-alkyl-β-naphthol products displayed high absorbance, emissive properties, and quantum yields (up to 93.2 %). Dearomative bromination on α-alkyl-β-naphthol is demonstrated as a synthetic application. Mechanistic studies indicate that the reaction involves an aldehyde intermediate. DFT studies support this finding and further reveal that a stoichiometric amount of base is required to make the aldol condensation as well as elementary steps required for regeneration of catalytically active species. In situ-generated water molecule from the aldol condensation reaction plays an important role in the regeneration of an active catalyst.

Indole-functionalized polythiourethane/tetrapodal shaped ZnO nanocomposites for eco-friendly marine biofouling control

Antifouling coatings for marine use are a widely employed method for controlling the settlement and growth of unwanted aquatic organisms on surfaces. In this study, indole derivative N-(1H-5-bromo indole-3-ylmethyl) acrylamide (BIAM)-functionalized polythiourethane (PTU)/tetrapodal shaped zinc oxide (t-ZnO) nanocomposites (PTU/BIAM/t-ZnO) were synthesized through a Friedel–Crafts Alkylation reaction, thiol-ene click reaction and polyaddition reaction. Nanocomposites' surface characteristics, such as surface free energy, chemical composition, and surface morphology were investigated here. The mechanical characteristics and antifouling properties of the coating materials were also considered. These nanocomposites exhibited not only superior mechanical properties, due to the presence of both PTU and t-ZnO, but also promising antifouling properties owing to the incorporation of BIAM on their surfaces. The adhesion strength of the nanocomposites increased from 0.26 MPa to 0.68 MPa due to the incorporation of t-ZnO particles. Benefiting from the PTU matrix, the tensile strength of nanocomposite can reach over 57 MPa. The PTU/BIAM/t-ZnO nanocomposites demonstrated improved algae resistance and marine antifouling performance compared to the reference PTU/t-ZnO nanocomposite without indole derivative. The PTU/BIAM/t-ZnO nanocomposites exhibit resistance to fouling organisms due to the synergistic effect of the easy-to-clean characteristic of the PTU/t-ZnO and the reduction of the polar component of the surface free energy resulting from the inclusion of indole derivative BIAM on the surface. This, in turn, reduces the interaction between fouling organisms and the material surface. Furthermore, BIAM interferes with the homeostasis of cellular calcium ions, thereby hindering the attachment of fouling organisms. Under the combined action of PTU, BIAM, and t-ZnO, the synergistic effect of good antifouling properties, environmental compatibility, good mechanical properties and strong adhesion to the substrate was achieved.

Recent Advances in Base‐Metal‐Catalyzed Carbonylation of Unactivated Alkyl Electrophiles†

Comprehensive SummaryTransition metal‐catalyzed carbonylation reactions represent a direct and atom‐economical approach to synthesize carbonyl compounds or their derivatives by using CO as a cheap and readily available C1 feedstock. While carbonylation of C(sp2)‐hybridized electrophiles (e.g., aryl halides) is well developed, carbonylation of less reactive unactivated alkyl electrophiles remains challenging. Recently, the use of earth‐abundant base metals including Cu, Co, Mn, Fe, Ni as catalysts has enabled advances in carbonylative coupling of alkyl electrophiles for approaching diverse carbonyl compounds or their derivatives, notably, some of which are of synthetic importance but difficult to be synthesized through previous reported methods. Herein, we have summarized and discussed these recent achievements in base‐metal‐catalyzed carbonylative C—C, C—N, C—O, C—X coupling and other carbonylation reactions of unactivated alkyl electrophiles using CO as C1 source.

Betainization of Polydopamine/Polyethylenimine Coating for Universal Zwitterionization.

Biofoulants can adhere to multiple surfaces, degrading the performance of medical devices and industrial facilities and/or causing nosocomial infection. The surface immobilization of zwitterionic materials can prevent the initial attachment of the foulants but lacks extensive implementation. Herein, we propose a facile, universal, two-step surface modification strategy to improve fouling resistance. In the first step, the substrates were immersed in a codeposition solution containing dopamine and branched polyethylenimine (PEI) to form a "primer" layer (PDA/PEI). In the second step, the primer layers were treated with 1,3-propane sultone to betainize primary/secondary/tertiary amine moieties of PEI, generating zwitterions on substrates. After betainization, PS-grafted PDA/PEI (PDA/PEI/S) via a ring-opening alkylation reaction manifested changes in wettability. X-ray photoelectron spectroscopy revealed the presence of zwitterionic moieties on the PDA/PEI/S surfaces. Further investigations using ellipsometry and atomic force microscopy were conducted to scrutinize the relation among the PEI content, film thickness, primer stability, and betainization. As a result, zwitterion-decorated substrates prepared under optimal conditions can exhibit high resistance against bacterial fouling, achieving a 98.5% reduction in bacterial attachment. In addition, the method shows a substrate-independent property, capable of successfully applying it on organic and inorganic substrates. Finally, the newly developed approach shows excellent biocompatibility, displaying no significant difference compared with blank control samples. Overall, we envision that the facile surface modification strategy can further promote the preparation of zwitterion-decorated materials in the future.

Catalytic asymmetric Friedel–Crafts alkylation of unprotected indoles with nitroalkenes using a novel chiral Yb(OTf)3–pybox complex

Chiral chloro-indeno pybox has served as a new ligand for the Yb(OTf)3-catalyzed asymmetric Friedel–Crafts alkylation reaction of indoles with nitroalkenes. The tunable nature of pybox ligands enables the rational design of catalysts for optimal performance in terms of both activity and stereoselectivity in a Friedel–Crafts-type reaction. Good to excellent yields and enantioselectivities were obtained for a relatively wide range of substrates, including sterically hindered compounds, under optimized reaction conditions.

Rh(III)‐Catalyzed Direct ortho Alkylation of Carbazoles with Nitroalkenes

AbstractThe Rh(III)‐catalyzed ortho alkylation of N‐pyridylcarbazoles with nitroalkenes has been developed, furnishing a wide range of 2‐(2‐nitroalkyl)carbazoles. Both aromatic and aliphatic nitroalkenes participated in this alkylation reaction successfully. This protocol also proceeded well with an indoline based substrate. Derivatization of the representative nitroalkane product was described.

Mesoporous Beta zeolites with controlled distribution of Brønsted acid sites for alkylation of benzene with cyclohexene

The distribution of Brønsted acid sites in three-dimensional 12-membered pore channels of Beta zeolite was a decisive factor in the alkylation of benzene with cyclohexene. Here, the Brønsted acid site distribution in Beta zeolitic channels was precisely regulated by tuning the content of Na+ in crystallization system combined with tetraethylammonium cation, the Beta-55 with Brønsted acid sites exclusively located in straight channels (along a- and b-axis directions) was successfully synthesized by utilizing tetraethylammonium as the structure-directing agents without Na+ species, and the fraction of Brønsted acid sites in sinusoidal/straight channels of Beta zeolites can be accurately controlled by tailoring the content of Na+ in synthesis gel. Catalytic properties in the liquid alkylation between benzene and cyclohexene exhibited that Beta-55 zeolites with the Brønsted acid sites solely located in a-axis and b-axis channels showed the highest cyclohexene conversion, cyclohexylbenzene selectivity and longest lifetime in this reaction. In addition, the resultant Beta zeolites also exhibited low coke generation rate and robust regeneration performance in the alkylation reaction.

Carbocation rearrangement, methyl migration, and long-range hydrogen transfer in phenyl fatty acid esters

Various isomers can be observed in the Friedel–Crafts alkylation of benzene. However, the mechanism and influence of these isomerization reactions were still unclear. In this work, several methyl phenylundecanoate were analyzed by gas chromatography–mass spectrometry to explore the isomerization of the Friedel–Crafts alkylation. The results showed that there were three isomerization reactions in the Friedel–Crafts alkylation reaction: five isomers of methyl 6–10-phenylundecanoate due to carbocation rearrangement, five isomers of methyl 6–9-methyldecanoate and methyl undecanoate due to methyl migration, and the loss of neutral alcohol molecular fragments due to hydrogen transfer. At higher reaction temperature, carbocation migration was more active and the formation of methyl undecanoate isomers was observed. There was a competitive relationship between the production of methyl undecanoate isomers and methyl phenylundecanoate isomers. In addition, the hydrogen transfer could be initiated in the presence of unsaturated bonds and alcohol molecules lost as a fragment. The hydrogen from the phenyl groups, which were at a different position on the carbon chain of fatty acid esters, could be transferred to the ester group. It was found that hydrogen could be transferred intramolecularly over a long range. This work revealed the isomerization process in the Friedel–Crafts alkylation and further deepened the understanding of alkylation.

Cisplatin Dependent Secretion of Immunomodulatory High Mobility Group Box 1 (HMGB1) Protein from Lung Cancer Cells.

High mobility group box 1 (HMGB1) is secreted from activated immune cells, necrotic cells, and certain cancers. Previous studies have reported that different patterns of post-translational modification, particularly acetylation and oxidation, mediate HMGB1 release and confer distinct extracellular HMGB1 signaling activity. Here we report that cisplatin but not carboplatin induces secretion of HMGB1 from human A549 non-small cell lung cancer (NSCLC) cells. Cisplatin-mediated HMGB1 secretion was dose-dependent and was regulated by nuclear exportin 1 (XPO1) also known as chromosomal maintenance 1 (CRM1) rather than adenosine diphosphate (ADP)-ribosylation, acetylation, or oxidation. HMGB1, as well as lysine acetylation and cysteine disulfide oxidation of secreted HMGB1, were monitored by sensitive and specific assays using immunoprecipitation, stable isotope dilution, differential alkylation, and nano liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry (nano-LC-PRM/HRMS). A major fraction of the HMGB1 secreted by low-dose cisplatin treatment of A549 NSCLC cells was found to be in the fully reduced form. In contrast, mainly oxidized forms of HMGB1 were secreted by dimethyl sulfoxide (DMSO)-mediated apoptosis. These findings suggest that inhibition of XPO1 could potentiate the anti-tumor activity of cisplatin by increasing the nuclear accumulation of HMGB1 protein, an inhibitor of cisplatin DNA-adduct repair. Furthermore, low-dose cisplatin therapy could modulate the immune response in NSCLC through the established chemokine activity of extracellular reduced HMGB1. This could potentially enhance the efficacy of subsequent immunotherapy treatment.

Synthesis of New Bioactive Triazolpyrimidine Derivatives Using Multicomponent Reactions of Hydrazonoyl Chloride

In this research, the preparation of 1,2,4-triazolpyrimidine derivatives was performed by using four component reactions of alkyl 2,4-dioxo-4-(arylamino) butanoate, aldehydes, cyanoguanidine, and hydrazonoyl chloride in the presence of catalytic amounts of Et3N in water at room temperature. In addition, for investigation of antioxidant activity was performed radical trapping by DPPH and reducing the power of ferric ion experiments. As a result, synthesized compounds show excellent radical trapping by DPPH and good reducing ability of ferric ion because of having NH2 group. The current procedure has benefits for instance excellent yield of reaction, green media, and easy separation of product.

Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions.

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.

Visible-Light-Induced Reductive Coupling of Arylacetylenes with Benzothiazole Sulfones.

In this study, we propose heavy-metal-free reductive coupling of arylacetylenes with benzothiazole sulfones. The reactions of alkyl or benzylic benzothiazole sulfones with arylacetylenes are successfully performed in the presence of Hantzsch esters and K2CO3 under visible-light irradiation to afford 1,2-disubstituted alkenes in moderate to good yields, with Z-isomer as the major product. The utility of this protocol is expanded to α-deuterative coupling using a deuterated Hantzsch ester, furnishing the corresponding alkenes with high deuterium incorporation.