C3 Alkylation Research Articles

Regulation of isobutane/1-butene adsorption behaviors on the acidic ionic liquids-functionalized MCM-22 zeolite

Abstract The adsorption ratio of isobutane/1-butene on the catalyst surface is one of the most important factors for the C4 alkylation process. Regulation of isobutane/1-butene adsorption ratio on the zeolite-supported acid catalyst is a big challenge for catalyst preparation. To regulate the isobutane/1-butene adsorption ratio, four types of ionic liquid (i.e., IL) with different alkyl chain lengths and different acid group numbers were synthesized and were subsequently immobilized onto the MCM-22 zeolite. The as-synthesized IL-immobilized MCM-22 (i.e., MCM-22-IL) was characterized by FTIR, TGA, BET, XPS and XRD, and their adsorption capacities and adsorption molar ratios of isobutane to 1-butene (I/O) were investigated to correlate with surface features of MCM-22-IL. Results showed that the immobilization of ILs led to a decrease of specific surface area and pore volume. But the surface density of acid groups was increased and the adsorption molar ratio of isobutane/1-butene (I/O) was significantly improved by the immobilization of ionic liquids. The adsorption molar ratio of I/O is substantially improved from 0.75 to above 0.9 at 300 kPa upon immobilizing ILs. Although the alkyl chain length of ILs was found to have little effect on the adsorption molar ratio of I/O, the increase of acid group numbers led to a dramatic decrease in the adsorption I/O ratio. The results illustrated that immobilizing ionic liquids is an effective way to modify the textural, chemical and morphological properties of MCM-22. Accordingly, the immobilization of ionic liquids provides a novel and a feasible way to regulate the adsorption I/O ratio on an adsorbent or a solid catalyst.

Ionic liquid [Dabco-C8][FeCl4] as an efficient and recyclable catalyst for direct C3 alkylation of indoles with electron-deficient olefins

In this paper, a simple and highly efficient Friedel–Crafts Michael–type addition of indoles to electron-deficient olefins was achieved by a new magnetic ionic liquid catalyst ([Dabco-C8][FeCl4]). This catalyst system is applicable to a variety of electron-deficient olefins, including chalcones, enones, and nitro-olefins, and affords the corresponding 3-alkylindole derivatives in good to excellent yields under mild conditions within short times. The catalyst can be recycled four times without considerable activity loss.

Modeling of the interfacial behaviors for the isobutane alkylation with C4 olefin using ionic liquid as catalyst

As a typical liquid/liquid interface reaction, the isobutane alkylation with C4 olefins produces C8 alkylates that are important as clean gasoline components. In this work, the interfacial properties between the hydrocarbons (reactants and/or products) and 1-butyl-3-methylimidazolium ionic liquids (ILs) with various anions corresponding to different acidity, including [Bmim][PF6], [Bmim][BF4], [Bmim][AlCl4] and [Bmim][Al2Cl7], have been investigated using molecular dynamics (MD) simulations. The density of the anions of ILs at interface was found to be about 10% higher than that in the bulk, which was favorable to the generation of carbonium at interface. The butyl groups of the cations tend to orient themselves perpendicular to the interface and protrude into the hydrocarbon mixtures phase, enhancing the dissolution of reactants at interface. It was also revealed that for the reactants, the molar fraction of 2-butene both in the bulk and at interface was much higher than that of isobutane, and 2-butene also had a larger diffusion coefficient at interface. However, for the product systems (isobutane+isooctane+IL), both the molar fraction and the diffusion coefficient of isobutane were obviously higher than that of isooctane. Compared to the neutral ILs, for the acidic ILs the binary hydrocarbon mixtures were easier to disperse into the IL phase with the mole fraction nearly 4 times higher in the bulk and about 1.2 times higher at interface. The difference in interfacial properties for various hydrocarbon-IL systems is in good agreement with the interaction energy between the hydrocarbons and the cations, as well as the anions of the ILs. Hopefully, the information concerning the IL-hydrocarbon interface at the molecular level obtained in this work can bring helpful insights into the C4 alkylation process catalyzed by the ILs.

Visible-Light-Induced C2 Alkylation of Pyridine N-Oxides.

A photoredox catalytic method has been developed for the direct C2 alkylation of pyridine N-oxides. This reaction is compatible with a range of synthetically relevant functional groups for providing efficient synthesis of a variety of C2-alkylated pyridine N-oxides under mild conditions. Mechanistic studies are consistent with the generation of a radical intermediate along the reaction pathway.

C3 Alkylation of Indoles Catalyzed by Carbocations under Continuous‐Flow Conditions

AbstractA fast and practical protocol for the C3 alkylation of varied indole substrates catalyzed by carbocations was developed under continuous‐flow conditions. Because of the enhanced mass‐ and heat‐transfer features of the microreactor, the reaction time was significantly reduced compared with batch conditions. The functional group tolerance of this method is good, the substrate scope for indoles and α,β‐unsaturated carbonyls is broad. In addition, the reactants were employed in the ratio of 1:1 to achieve good to excellent yields. It is an effective reaction to cut down chemical waste and is of benefit for environment protection from an industrial production point of view.

Asymmetric Total Syntheses of Aspidodasycarpine, Lonicerine, and the Proposed Structure of Lanciferine.

Aspidodasycarpine and lonicerine are a pair of epimeric aspidophylline-type alkaloids bearing vicinal quaternary C7 and C16. The first and enantioselective total syntheses of these molecules are described here. A Ru-catalyzed asymmetric transfer hydrogenation established the first stereocenter. An Au-promoted Toste cyclization was exploited to assemble the bridged tetracyclic core and define the geometry of the exocyclic olefin; electron deficient (p-CF3C6H4)3P was a suitable ligand for this transformation. An aldol condensation followed by an intramolecular indole C3 alkylation constructed the adjacent quaternary C7 and C16 diastereoselectively, leading to a pentacyclic lactol as an advanced common intermediate for synthesizing both alkaloids. The proposed structure of lanciferine, a highly oxidized congener of aspidodasycarpine, was synthesized from the lactol by tuning the oxidation states of various carbons.

Sequential one-pot Rh(III)-catalyzed direct C2 and C7 alkylation of (hetero)aromatic C–H bonds of indoles

A simple and versatile method for highly efficient synthesis of various polysubstituted indoles via a sequential one-pot Rh(III)-catalyzed direct C2–H and C7–H alkylation with diazo compounds has been developed. This process features with mild reaction conditions, wide substrate scope, and good functional group tolerance (24 examples, up to 96% yield).

Anchoring via covalent binding of β-diimine-nickel complexes in SBA-15 and its application in catalytic reactions

The β-diimine ligands 2-(phenyl)amine-4-(phenyl)imine-2-pentene (L1) and 2-(2,6-dimethylphenyl)amine-4-(2,6-dimethylphenyl)imine-2-pentene (L2) were anchored covalently to SBA-15. The ligands were combined with (3-chloropropyl) trimethoxysilane (CPTMS), which is a trialkoxysilane group, and anchored to a mesoporous SBA-15 support through a complexation of the silanols of the silica matrix with nickel. These complexes were synthesized as catalysts precursors for ethylene and propylene oligomerization processes. The support was first synthesized and calcined before being anchored to the ligand, generating the nickel complex. These materials were characterized using various techniques such as 13C and 29Si NMR, small angle XRD, thermogravimetric analysis, N2 adsorption, transmission electron microscopy, elemental analysis and flame atomic absorption spectroscopy. The heterogenized complexes are active and selective during ethylene and propylene oligomerization, generating C4 and C6 products and alkylation products ranging from C10–C16. The alkylation process being a parallel reaction. The Ni-β-diimine/SBA-15 (SC1) complexes showed an activity of 7.2×103h−1 for the ethylene oligomerization with 98% selectivity toward α- and C4 products and an activity of 2×103h−1for the propylene oligomerization with a 13% selectivity toward C6 linear products. The results of the oligomerization reactions reveal the influence of the support on the products obtained.

Ruthenium-catalyzed direct C3 alkylation of indoles with α,β-unsaturated ketones.

In this paper, a simple and highly efficient ruthenium-catalyzed direct C3 alkylation of indoles with various α,β-unsaturated ketones without chelation assistance has been developed. This novel C-H activation methodology exhibits a broad substrate scope such as different substituted indoles, pyrroles, and other azoles. Further synthetic applications of the alkylation products can lead to more attractive 3,4-fused tricyclic indoles.

Diethylzinc-Promoted Synthesis of Trifluromethyl-Containing Tryptamine Analogues from Indoles and 2-Trifluromethyl-N-(4-Toluenesulfonyl)-Aziridine

Incorporation of fluorine atoms into biologically active organic molecules often causes enhancement of activity, stability, and solubility, as well as reduction of toxicity. Tryptamine derivatives are known for important medicines concerning our mental health. Therefore, fluorinated tryptamine derivatives could be promising medicinal candidates for pharmaceutical chemistry. We have already reported the regioselective ring-opening reaction of 2-CF3-N-Ts-aziridine (Ts=4-toluenesulfonyl) with some nucleophiles. If this ring-opening reaction proceeds smoothly at the C3 position of indoles, it could provide a solution for the synthesis of CF3-containing tryptamine analogues. We examined the diethylzinc-promoted direct C3 alkylation of indoles with 2-CF3-N-Ts-aziridine under basic conditions. We have developed the synthesis of CF3-tryptamine from 2-CF3-N-Ts-aziridines and indoles by using diethylzinc as a base with excellent yields and complete regioselectivity.

Catalytic Friedel–Crafts Reaction of Aminocyclopropanes

A Lewis acid catalyzed Friedel-Crafts reaction between donor-acceptor aminocyclopropanes and indoles and other electron-rich aromatic compounds is reported. Indole alkylation at the C3 position was generally obtained for a broad range of functional groups and substitution patterns. In the case of C3-substituted indoles, C2 alkylation was observed. The reaction gives a rapid access to gamma amino acid derivatives present in numerous bioactive molecules.

Chlorogallate(III) ionic liquids: Synthesis, acidity determination and their catalytic performances for isobutane alkylation

A series of triethylammonium-based chlorogallate(III) ionic liquids with varied Lewis acidity was synthesized, characterized, and firstly applied to isobutane alkylation. The [Et3NHCl]-GaCl3 with \(\chi _{GaCl_3 } \) = 0.65 displayed a potential catalytic activity for the alkylation. The addition of copper halide into the chlorogallate(III) ionic liquids dramatically enhanced the alkylation reaction. Up to 70.1% C8 selectivity and 91.3 RON were achieved with the [Et3NHCl]-GaCl3-CuCl (\(\chi _{GaCl_3 } \) = 0.65, CuCl = 5% mol) under 0.5 MPa, 900 r/min, 15 min, 288 K using the industrial C4 cut (isobutane/butene = 10). These results indicate that the chlorogallate(III) system may be used as a promising catalyst for the C4 alkylation.

Asymmetric N‐Allylation of Indoles Through the Iridium‐Catalyzed Allylic Alkylation/Oxidation of Indolines

The synthesis of enantiopure indole derivatives is of significant importance because optically active indole moieties are a common occurrence in bioactive natural products and pharmaceuticals. To this end, enormous efforts have been devoted to the development of catalytic asymmetric reactions of indoles in the past decade. It has been well documented that the C3-position of an indole is the most reactive one among the three positions (N1, C2, C3) under the conditions of the Friedel–Crafts reaction. Recently, the enantioselective C2 alkylation of indoles was realized through variations of the Pictet–Spengler reaction, alkylation of 2-indolyl trifluoroborate salts, and alkylation/oxidation of 4,7-dihydroindoles. However, the enantioselective N-substitution of indoles has rarely been explored due to the weak acidity of the N H group, despite the fact that the products are privileged structural motifs in natural alkaloids and biologically active compounds (Figure 1).

A Concise Synthesis of 6H-Indolo[2,3-b]quinolines: Formal Synthesis of Neocryptolepine

A new two-step approach for the synthesis of 6H-indolo[2,3-b]quinolines is described using indole C3 alkylation and a one-pot reduction–cyclization–aromatization sequence. The synthesis of the parent 6H-indolo[2,3-b]quinoline system constitutes a formal synthesis of the alkaloid neocryptolepine (cryptotackieine).

Radical Chemistry of Iminepyridine Ligands

AbstractThe reactivity of metal fragments MeLi(THF), Me2Mg, Me2Zn and Me3Al with a variety of imine/pyridine ligands was studied by DFT methods. Ligands having at least two such groups in conjugation very effectively accept an electron from a metal–carbon bonding orbital and thus assist alkyl dissociation: the M–Me dissociation free energy ΔGd decreases by about 45 kcal/mol for the Li, Mg and Zn fragments, and by 60–70 kcal/mol for Me3Al. Paths for transfer of an alkyl group to the ligands were also explored. Paths for transfer to ligand carbon atoms were found to have high barriers, and such transfers are instead proposed to proceed via initial M–Me dissociation. Direct alkyl transfer to ligand nitrogen atoms is somewhat easier, and for the most electropositive metal Li such a transfer might compete with radical chemistry. For Dimpy, the most stable products are the C3 and C4 alkylation ones. However, the observed regioselectivity of alkyl transfer (often to Npy or C2) does not correlate with product stability and is likely to be a complicated function of radical stability, steric factors and unpaired electron density distribution. The results illustrate that Dimpy and related ligands should be considered strong, reversible oxidants.

A cycloisomerization/Friedel-Crafts alkylation strategy for the synthesis of pyrano[3,4-b]indoles.

The synthesis of pyrano[3,4-b]indoles is described. The reaction sequence involves Sonogashira coupling of dihydropyran propargyl ether scaffolds with iodoanilines to afford intermediate indoles. Lewis acid-catalyzed ionization of the dihydropyrans, followed by intramolecular C3 alkylation of the indole, provides the title compounds.

Selective C4 Alkylation of Pyridines Using Nickel/Lewis Acid Catalysis

A direct C4-selective addition of pyridine across alkenes via nickel/Lewis acid ­cocatalysis has been described. The method ­proceeds highly regioselectively furnishing the ­linear 4-alkylpyridines in modest to good yields. Branched 4-alkylpyridines are obtained when ­styrenes are used.

Tris(pentafluorophenyl)borane-Catalyzed Alkylation of 1,3-Dicarbonyl Compounds with Benzylic Alcohols: Access to Oxygenated Heterocycles

Tris(pentafluorophenyl)borane has found to be an effective catalyst for the alkylation of 1,3-dicarbonyl compounds using benzylic alcohols as alkylating agents. Various 1,3-dicarbonyl compounds reacted cleanly with different benzylic alcohols to provide the corresponding monoalkylated products in good yield. In addition tris(pentafluorophenyl)borane efficiently promoted the C3 alkylation of 4-hydroxycoumarins. Further, several oxygenated heterocycles such as furans, 4H-chromenes, and furanocoumarins have been prepared using the described methodology as the key step.

Reaction of the Diimine Pyridine Ligand with Aluminum Alkyls: An Unexpectedly Complex Reaction

The diimine pyridine ligand 2,6-{2,6-iPr2C6H3NCMe}2C5H3N (1) was reacted with a series of aluminum alkyls (Me3Al, Et3Al, iBu3Al, iBu2AlH, Et2AlCl). Depending on the choice of alkyl, addition to the imine carbon and the pyridine C2 and C4 positions was observed. Addition to C2 usually dominates but is reversible; the C4 alkylation product eventually dimerizes via double C−C coupling. Reaction of 1 with AlCl3 gave the ionic complex [1·AlCl2]+[AlCl4]-. DFT calculations were used to support NMR assignments of the various addition products and also to study alkyl transfer from Et2AlCl to simplified model ligand 1‘. Direct alkyl transfer from coordinated Et2AlCl to the ligand C4 position is not possible. Introduction of a second molecule of Et2AlCl results in formation of the ion pair [1‘·AlEtCl]+[Et3AlCl]-, from which alkyl transfer to any position of the ligand is relatively easy. The dimerization of the C4-alkylated product is symmetry-forbidden and was calculated to follow a stepwise biradical path with an unusually low barrier.

Highly Enantioselective Synthesis of Rigid, Quaternary 1,4-Benzodiazepine-2,5-diones Derived from Proline

[reaction: see text] Proline-derived 1,4-benzodiazepine-2,5-diones are extremely useful scaffolds in medicinal chemistry. In this paper, we describe a protocol for retentive C3 alkylation of these materials, thus accomplishing the direct synthesis of enantiopure quaternary 1,4-benzodiazepine-2,5-diones. The high enantioselectivities (up to 99.5%) are attributed to memory of chirality.