Alkylation Products Research Articles

BODIPY derivatives as light-induced free radical generators for hypoxic cancer treatment

NBDP can self-assemble into nanoparticles (NBDP NPs), which could be internalized by cells via endocytosis. After being irradiated with an 808 nm laser, the BODIPY unit could convert photons into heat and further initiates the production of alkyl radicals. The generated tumor hyperthermia and alkyl radicals synergistically kill cancer cells.

Iridium/N-Heterocyclic Carbene Complex-Catalyzed Intermolecular Allylic Alkylation Reaction

N-Heterocyclic carbenes (NHCs) were found to be suitable ligands in Ir-catalyzed intermolecular allylic alkylation reaction. In the presence of a catalyst derived from [Ir(dncot)Cl]2 (dncot = dinaphthocyclooctatetraene) and triazolium salt L7, the alkylation products from the reaction of aryl allyl carbonates with sodium dialkyl malonates could be obtained in 85–99% yields favoring the formation of branched products (90/10 → >99/1 b/l). In addition, chiral dihydroisoquinoline-type NHC (DHIQ-NHC) (L8) is successfully applied in Ir-catalyzed asymmetric allylic alkylation reactions. Excellent enantioselectivities and moderate regioselectivities were obtained for a wide range of substrates.

On the Stability of Disubstituted Cyclobutenes - A Computational Study.

A computational study of the electrocyclic ring‐opening of 2‐substituted cyclobutenecarboxylic acids is presented. Detailed calculations suggest a model to predict whether the product of nucleophilic alkylation of a bicyclic lactone electrophile will be a cyclobutenecarboxylic acid or its dienoic acid isomer, based on the used nucleophile.

Influence of the Binder Type on the Properties of Nanocrystalline Zeolite Beta-Based Catalysts for Benzene Alkylation with Propylene

The effect of different binders (aluminum hydroxide (sample K-1), silica gel (sample K-2), pseudoboehmite (sample K-3), a kaolin–silica sol mixture (sample K-4), and a kaolin–aluminum hydroxide mixture (sample K-5)) on the set of the textural, acidic, and catalytic properties of catalysts based on nanocrystalline zeolite Beta has been studied. It has been shown that the introduction of aluminum hydroxide, silica gel, and a kaolin–aluminum hydroxide mixture as binders does not lead to the blocking of the pore structure of the zeolite, while the introduction of pseudoboehmite and a kaolin–silica sol mixture into the catalyst composition leads to a decrease in the micropore volume. Using the NH3 TPD method, it has been found that the use of aluminum hydroxide, pseudoboehmite, and a kaolin–aluminum hydroxide mixture as a binder leads to an increase in the number of acid sites of the catalyst compared with the respective parameter of the original BEA-25 zeolite. The observed changes are attributed to the migration of aluminum from the binder to the zeolite structure to form new acid sites, as evidenced by 27Al MAS NMR data. It has been assumed that an increase in acidity for the K-4 sample is associated with the interaction of silica with the extra-framework aluminum of the Beta zeolite. With respect to activity in the benzene alkylation with propylene, the catalysts can be arranged in the following order: K-1 > K-3 > K-2 > K-5 ≈ BEA > K-4, which correlates with the number of acid sites in the samples. The best process parameters have been achieved in the presence of the K-1 sample exhibiting a stable on-stream behavior for 10 h and providing a selectivity for alkylation products (cumene + DIPB) of 99.7% and a cumene selectivity of 89.7 wt % at 100% propylene conversion.

Synthesis of an adenine N-3 substituted CBI adduct by alkylation of adenine with a 1-iodomethylindoline seco-CBI precursor

The synthesis of a 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI)-adenine adduct via regioselective N-3 alkylation of adenine with a 1-(iodomethyl)-2,3-dihydro-1H-benzo[e]indol-5-ol (I-seco-CBI)-containing precursor is described. Spectroscopic analyses of the unlabeled and adenine-C8 carbon-13 labeled adducts utilizing ROESY NMR techniques allowed structural assignment of the alkylation product as the adenine N-3 substituted regioisomer. A stable-isotopically labeled version of the N-3 adduct incorporating six carbon-13 labels was also prepared by this method for use as an LC-MS internal standard. The cyclized CBI-containing compound was also found to alkylate adenine at elevated temperatures to produce the N-3 adduct albeit at a significantly slower rate than that observed for the I-seco-CBI precursor. Adenine alkylation with an I-seco-CBI precursor offers scalable and facile access to a CBI-adenine adduct facilitating its use as an efficacy marker for the development of duocarmycin-based ADCs.

Design and Synthesis of Zirconium‐Containing Coordination Polymer Based on Unsymmetric Indolyl Dicarboxylic Acid and Catalytic Application on Borrowing Hydrogen Reaction

AbstractCatalytic borrowing hydrogen reaction is a very attractive transformation in the field of C‐alkylation reaction. In this work, a new Zr (Zirconium)‐containing coordination polymer containing unsymmetric indolyl dicarboxylic acid 1‐(carboxymethyl)‐1H‐indole‐5‐carboxylic acid (H2CIA) was synthesized by the way of a solvothermal synthetic route and characterized by powder X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Nitrogen adsorption‐desorption, fourier transform infrared spectroscopy and X‐ray photoelectronic spectroscopy (XPS). The coordination polymer Zr‐CIA was employed as the catalyst for C‐alkylation of acetophenone derivatives in the presence of benzyl alcohol. In addition, Zr‐CIA catalyst was also observed to be effective in the reaction of alcohols with alcohols and high yields of alkylation products were achieved. Mechanism investigations were also conducted to better understand the catalysts and transformations. Meanwhile, the Zr‐CIA could be reused at least five times without a notable decrease in activity and selectivity.magnified image

Enantioselective Friedel-Crafts Alkylation Reactions of β-Naphthols with Donor-Acceptor Aminocyclopropanes.

The enantioselective Friedel-Crafts alkylation reaction of β-naphthols with donor-acceptor aminocyclopropane was developed. In the presence of a copper complex derived from Cu(OTf)2 and bisoxazoline, a series of γ-substituted γ-aminobutyric acid derivatives were obtained with good yields (up to 98 %) and excellent enantioselectivities (up to 98 %). Using this catalytic system, the 2-amino cyclopropane-1,1-dicarboxylate was obtained with high enantiomeric excess (up to 98 %) by an efficient kinetic resolution (s values of up to 90). The Friedel-Crafts alkylation product could be transformed into a tetracyclic 1,3-oxazine derivative.

Alkylation versus trans-silylation of N-methyl-N-trimethylsilylacetamide with ambident electrophiles (chloromethyl)fluorosilanes

Bifunctional silanes ClCH2SiF3 and ClCH2SiF2Me react with N-trimethylsilyl-N-methylacetamide and its tautomer О-trimethylsilyl-N-methylacetimidate as ambident substrates to give the products of trans-silylation N-{[chloro(difluoro)silyl]methyl}-N-methylacetamide and N-{[chloro(fluoro)methylsilyl]methyl}-N-methylacetamide with liberation of Me3SiF, as well as the products of alkylation N-methyl-N-[(trifluorosilyl)methyl]acetamide and N-{[difluoro(methyl)silyl]methyl}-N-methylacetamide with liberation of Me3SiCl. The reaction takes place at room temperature in solvents such as CDCl3, CD3CN or hexane. Under these conditions silane ClCH2SiFMe2 with amide gives only the product of trans-silylation, N-{[chloro(dimethyl)silyl]methyl}-N-methylacetamide. The reactions of trans-silylation and alkylation were monitored and the products and reaction intermediates analyzed by NMR and IR spectroscopy. For all possible reaction routes, quantum-chemical calculations were performed including the analysis of transition states.

Amberlyst-15 as a Green and Efficient Reusable Catalyst for Friedel-Crafts Alkylation of Activated Arenes with N -Sulfonyl Aldimines and Synthesis of Bis-triarylmethanes

Amberlyst-15 has been found to be an efficient and an inexpensive acidic heterogeneous catalyst for Friedel–Crafts alkylation of an activated arenes and N-sulfonyl aldimines at room temperature. A Friedel-Crafts alkylation products further undergoes alkylation with another mole of activated arenes to afford bis-triarylmethanes in single transformation. Non-toxicity and high stability of catalyst, broad applicability to various substrates with good to high yields and a simple operational procedure are the major advantages of the present method. The catalyst can be easily recycled by simple filtration and reused consecutively four times times without significant loss of activity.

Hydroarylations by cobalt-catalyzed C-H activation.

As an earth-abundant first-row transition metal, cobalt catalysts offer a broad range of economical methods for organic transformations via C–H activation. One of the transformations is the addition of C–H to C–X multiple bonds to afford alkylation, alkenation, amidation, and cyclization products using low- or high-valent cobalt catalysts. This hydroarylation is an efficient approach to build new C–C bonds in a 100% atom-economical manner. In this review, the recent developments of Co-catalyzed hydroarylation reactions and their mechanistic studies are summarized.

Synthesis of high-performance jet fuel blends from biomass-derived 4-ethylphenol and phenylmethanol

Bicyclic and multi-cyclic hydrocarbons usually have high density over 0.87 g/cm3, which is very popular to synthesize from biomass-derived renewable chemicals, but their cryogenic properties need to be further improved for practical applications. In this work, we synthesized ethyl-substituted bicyclic high-performance hydrocarbons with improved cryogenic properties from the biomass-derived 4-ethylphenol and phenylmethaol. For the alkylation reaction between 4-ethylphenol with phenylmethanol, the reaction conditions were optimized, under which the conversion of phenylmethanol can achieve 100% with monoalkylated products (2-benzyl-4-ethylphenol and 3-benzyl-4-ethylphenol) selectivity of 71%. After hydrodeoxygenation catalyzed by a mixture catalyst of Pd/C and HZSM-5, the alkylation products were mainly converted to the ethyl-substituted dicyclohexylmethane. The obtained fuel shows a high density of 0.873 g/cm3 (20 °C), gravimetric net heat of combustion of 42.7 MJ/kg, and the freezing point of −42 °C, which is promising to serve as a blend component for jet fuel application.

Enantioselective Alkylation of N-Arylhydrazones Derived from α-Keto Esters and Isatin Derivatives through Asymmetric Phase-Transfer Catalysis.

The phase-transfer-catalyzed asymmetric alkylation reactions of N-arylhydrazones derived from α-keto-esters and isatin derivatives afford enantioenriched azo compounds that bear a tetra-substituted carbon stereocenter in good yields with high chemo- and enantioselectivity. The alkylation products can be readily converted into chiral amino esters, hydrazine derivatives, and aza-β-lactams without loss of enantiopurity.

Comparative Evaluation of Zeolite Catalysts of Benzene Alkylation

Using the benzene alkylation reaction with propylene, the catalytic properties of heterogeneous catalysts are compared under conditions of simultaneous action of permanent deactivating factors (atmospheric pressure, increased volume feed rate) on the samples under study. For a comparative evaluation of the tested catalysts, a mathematical analysis of the experimental data on the concentration of the desired alkylation product vs. the time of the catalyst operation was carried out, and a corresponding empirical formula was derived. To compare the activity of catalysts, the power coefficient of the function was proposed as a catalyst activity factor f. A relationship between the value of this factor and the rate of deactivation of the catalyst under the conditions of the experiments was derived.

Synthesis of N-Substituted Methyl 4H-Thieno[3,2-b]pyrrole-5-carboxylates

The alkylation of methyl 4H-thieno[3,2-b]pyrrole-5-carboxylate with methyl iodide and allyl, propargyl, and benzyl bromides in the presence of sodium hydride in THF afforded the corresponding N-substituted derivatives. Some reactions of the alkylation products were studied.

Cytotoxic and mutagenic properties of minor-groove O2-alkylthymidine lesions in human cells

Endogenous metabolism, environmental exposure, and cancer chemotherapy can lead to alkylation of DNA. It has been well documented that, among the different DNA alkylation products, minor-groove O2-alkylthymidine (O2-alkyldT) lesions are inefficiently repaired. In the present study, we examined how seven O2-alkyldT lesions, with the alkyl group being a Me, Et, nPr, iPr, nBu, iBu, or sBu, are recognized by the DNA replication machinery in human cells. We found that the replication bypass efficiencies of these lesions decrease with increasing length of the alkyl chain, and that these lesions induce substantial frequencies of T→A and T→G mutations. Replication experiments using isogenic cells deficient in specific translesion synthesis (TLS) DNA polymerases revealed that the absence of polymerase η or polymerase ζ, but not polymerase κ or polymerase ι, significantly decreased both the bypass efficiencies and the mutation frequencies for those O2-alkyldT lesions carrying a straight-chain alkyl group. Moreover, the mutagenic properties of the O2-alkyldT lesions were influenced by the length and topology of the alkyl chain and by TLS polymerases. Together, our results provide important new knowledge about the cytotoxic and mutagenic properties of O2-alkyldT lesions, and illustrate the roles of TLS polymerases in replicative bypass of these lesions in human cells.

Carbon dioxide assisted toluene side-chain alkylation with methanol over Cs-X zeolite catalyst

Zeolite Cs-X is an acknowledged representative basic catalyst useful for side-chain alkylation of toluene with methanol. In spite of numerous investigations, still there has been long lasting challenge for achieving high selectivity for side-chain alkylated products rather than ring alkylated products. In an effort to improve the yields of side-chain alkylated products, CO2 was introduced during the toluene side-chain alkylation with methanol at 425 °C over Cs loaded faujasite catalyst. The CO2 addition facilitated in removing the formed hydrogen by reverse water-gas shift reaction and enhanced the product yield. Interestingly, CO2 addition helped in obtaining higher yields of side-chain alkylation products including styrene/ethylbenzene and α-methylstyrene/iso-propylbenzene. The CO2 introduction resulted in less H2 formation in the product stream during the reaction. Mesoporosity was also introduced to the zeolite X to improve the activity and product selectivity.

Mechanism and Origins of Stereoinduction in an Asymmetric Friedel-Crafts Alkylation Reaction of Chalcone Catalyzed by Chiral N, N'-Dioxide-Sc(III) Complex.

The mechanism and selectivity of the asymmetric Friedel-Crafts (F-C) alkylation reaction between indole and chalcone catalyzed by chiral N, N'-dioxide-Sc(III) complexes were investigated at the M06/6-311+G(d,p)//M06/[LANL2DZ,6-31G(d)](SMD,CH2Cl2) level. The reaction occurred via a three-step mechanism: (i) the C3-Cβ bond formation by interacting the most mucleophilic C3 center of indole with the most electrophilic Cβ center of chalcone; (ii) the abstraction of the proton at the C3 atom of indole by counterion OTf-; (iii) proton transfer from HOTf to the Cα atom of chalcone, generating the F-C alkylation product. The reaction preferred to occur along the favorable re-face attack pathway, producing the dominant R-product. The turnover frequency (TOF) of catalysis was predicted to be 1.59 × 10-7 s-1, with a rate constant of K( T) = 1.58 × 10-7 exp(-29057/ RT) dm6·mol-2·s-1 over the temperature range of 248-368 K. Activation strain model (ASM) and energy decomposition analysis (EDA), as well as noncovalent interaction (NCI) analysis, for the stereocontrolling transition state revealed that the substituent attached to the N atom of the amide subunits as well as the amino acid backbone of ligand played important roles in chiral inductivity. The benzyl group with structural flexibility tended to form strong π-π stacking with substrate as well as the terminal phenyl group of chalcone, stabilizing re-face attack transition state.

Cytotoxic and mutagenic properties of alkyl phosphotriester lesions in Escherichia coli cells.

Exposure to many endogenous and exogenous agents can give rise to DNA alkylation, which constitutes a major type of DNA damage. Among the DNA alkylation products, alkyl phosphotriesters have relatively high frequencies of occurrence and are resistant to repair in mammalian tissues. However, little is known about how these lesions affect the efficiency and fidelity of DNA replication in cells or how the replicative bypass of these lesions is modulated by translesion synthesis DNA polymerases. In this study, we synthesized oligodeoxyribonucleotides containing four pairs (Sp and Rp) of alkyl phosphotriester lesions at a defined site, and examined how these lesions are recognized by DNA replication machinery in Escherichia coli cells. We found that the Sp diastereomer of the alkyl phosphotriester lesions could be efficiently bypassed, whereas the Rp counterparts moderately blocked DNA replication. Moreover, the Sp-methyl phosphotriester induced TT→GT and TT→GC mutations at the flanking TT dinucleotide site, and the induction of these mutations required Ada protein, which is known to remove efficiently the methyl group from the Sp-methyl phosphotriester. Together, our study provided a comprehensive understanding about the recognition of alkyl phosphotriester lesions by DNA replication machinery in cells, and revealed for the first time the Ada-dependent induction of mutations at the Sp-methyl phosphotriester site.

Development and application of composite ionic liquid catalyzed isobutane alkylation technology

Alkylate from isobutane alkylation is an ideal blending component of motor gasoline. In China its blending ratio in gasoline is continuously increased with upgrading the gasoline quality standards. A series of studies on ionic liquid catalyzed isobutane alkylation were carried out around a new industrial process of alkylate production. The composition, structure and catalytic performance of chloroaluminate ionic liquids were studied, and a composite ionic liquid (CIL) with high catalytic activity and high selectivity was designed and synthesized. The deactivation mechanism of CIL during isobutane alkylation was studied and a feasible regeneration scheme was developed, including a Lewis acid activity monitoring method of chloroaluminate ionic liquids. A long period (2 months) operation test was carried out in a pilot plant, and then the initial process development of CIL catalyzed isobutane alkylation technology (CILA) was completed. A new type static mixing reactor and a hydrocyclone were developed. The first industrial plant of CILA was designed and constructed. The plant includes feed pretreatment, alkylation reaction, catalyst regeneration, product separation and clean-up systems. The industrial operation results were excellent. Butene conversion reached 100%, research octane number of alkylate maintained stably at above 95 and could reached up to above 98 at optimal operating conditions, end boiling point of alkylate was below 198 °C, and Cl content in alkylate was below 5 mg/L. CILA can produce clean alkylate with clean process, having a good application prospect and promotion value.

Enantiospecific Three-Component Alkylation of Furan and Indole.

Furan‐ and indole‐derived boronate complexes react with alkyl iodides under radical (photoredox) or polar (SN2) conditions to generate three‐component alkylation products with high efficiency and complete stereospecificity. The methodology allows the incorporation of versatile functional groups such as nitriles, ketones, esters, sulfones, and amides, providing rapid access to complex chiral heteroaromatic molecules in enantioenriched form. Interestingly, while indolyl boronate complexes react directly with alkyl halides in a polar pathway, furyl boronates require photoredox catalysis. Careful mechanistic analysis revealed that the boronate complex not only serves as a substrate in the reaction but also acts as a reductive quencher for the excited state of the photocatalyst.