Formation Of Carbocation Research Articles

Enhancement of Push–Pull Properties of Pentafulvene and Pentafulvalene Derivatives by Protonation at Carbon

We report visible color changes and new intense, bathochromically shifted bands in electronic absorption spectra that reach into the near‐infrared region (up to 862 nm) upon protonation of nine pentafulvene and expanded pentafulvalene derivatives. This phenomenon can only be explained by the formation of carbocations with highly delocalized charges. Solution pKa values in organic solvents were determined, making use of the method of relative basicity measurements. All seven 6‐phenylpentafulvenes are weak bases, and pKa values of the protonated forms range from 0.92 to 10.29 in acetonitrile and from 1.3 to 5.9 in 1,2‐dichloroethane. For 6‐phenylfulvenes with varying para‐substituents on the phenyl ring, pKa values correlate well with the Hammett parameters σpara. Furthermore, for most compounds, electrochemical reduction is significantly facilitated by protonation. Extensive theoretical and NMR studies strongly support the postulated protonation at carbon.

Theoretical Study of Sesterfisherol Biosynthesis: Computational Prediction of Key Amino Acid Residue in Terpene Synthase

The cyclization mechanisms involved in the biosynthesis of sesterterpenes are not fully understood. For example, there are two plausible reaction pathways for sesterfisherol biosynthesis, which differ in the order of ring cyclization: A-D-B/C (Path a) and A-B-C/D (Path b). It is difficult to capture intermediates of terpene cyclization, which is a complex, domino-type reaction, and so here we employed a combination of experimental and computational methods. Density functional theory calculations revealed unexpected intermediates and transition states, and implied that C–H···π interaction between a carbocation intermediate and an aromatic residue of sesterfisherol synthase (NfSS) plays a critical role, serving to accelerate the 1,2-H shift (thereby preventing triquinane carbocation formation) and to protect reactive carbocation intermediates from bases such as pyrophosphate or water in the active site. Site-directed mutagenesis of NfSS guided by docking simulations confirmed that phenylalanine F191 is a critical amino acid residue for sesterfisherol synthase, as the F191A mutant of NfSS produces novel sesterterpenes, but not sesterfisherol. Although both pathways are energetically viable, on the basis of our computational and experimental results, NfSS-mediated sesterfisherol biosynthesis appears to proceed via Path a. These findings may also provide new insight into the cyclization mechanisms in related sesterterpene synthases.

Metal-free alkene oxy- and amino-perfluoroalkylations via carbocation formation by using perfluoro acid anhydrides: unique reactivity between styrenes and perfluoro diacyl peroxides.

We present a strategy for metal-free, alkene difunctionalization-type, oxy- and amino-perfluoroalkylations, using perfluoro acid anhydrides as practical and user-friendly perfluoroalkyl sources. This method provides efficient access to oxy-perfluoroalkylation products via carbocation formation due to the unique reactivity between styrenes and bis(perfluoroacyl) peroxides generated in situ from perfluoro acid anhydrides. This reaction is also applicable to metal-free intramolecular amino-perfluoroalkylation of styrenes bearing a pendant amino group. Synthetic utility of the oxy-trifluoromethylation products was confirmed by demonstrating derivatization via hydrolysis, elimination, and acid-catalyzed substitution with carbon nucleophiles. The mechanism of the carbocation formation was investigated experimentally and theoretically.

Controlling factors of oligomerization at the water surface: why is isoprene such a unique VOC?

Recent studies have shown that atmospheric particles are sufficiently acidic to enhance the uptake of unsaturated volatile organic compounds (VOCs) by triggering acid-catalyzed oligomerization. Controlling factors of oligomerization at the aqueous surfaces, however, remain to be elucidated. Herein, isoprene (2-methyl-1,3-butadiene, ISO), 1,3-butadiene (1,3-b), 1,4-pentadiene (1,4-p), 1-pentene (1-p), and 2-pentene (2-p) vapors are exposed to an acidic water microjet (1 ≤ pH ≤ 5), where cationic products are generated on its surface within ∼10 μs and directly detected using surface-sensitive mass spectrometry. We found that carbocations form at the air-water interface in all the cases, whereas the extent of oligomerization largely depends on the structure in the following order: ISO ≫ 1,3-b > 1,4-p ≫ 1-p ≈ 2-p. Importantly, the cationic oligomerization of ISO yields a protonated decamer ((ISO)10H+, a C50 species of m/z 681.6), while the pentenes 1-p/2-p remain as protonated monomers. We suggest that ISO oligomerization is uniquely facilitated by (1) the resonance stabilization of (ISO)H+ through the formation of a tertiary carbocation with a conjugated C[double bond, length as m-dash]C bond pair, and (2) π-electron enrichment induced by the neighboring methyl group. Experiments in D2O and D2O : H2O mixtures revealed that ISO oligomerization on the acidic water surface proceeds via two competitive mechanisms: chain-propagation and proton-exchange reactions. Furthermore, we found that ISO carbocations undergo addition to relatively inert 1-p, generating hitherto uncharacterized co-oligomers.

Protonation-Initiated Cyclization by a Class II Terpene Cyclase Assisted by Tunneling.

Terpenes represent one of the most diversified classes of natural products with potent biological activities. The key to the myriad of polycyclic terpene skeletons with crucial functions in organisms from all kingdoms of life are terpene cyclase enzymes. These biocatalysts enable stereospecific cyclization of relatively simple, linear, prefolded polyisoprenes by highly complex, partially concerted, electrophilic cyclization cascades that remain incompletely understood. Herein, additional mechanistic light is shed on terpene biosynthesis by kinetic studies in mixed H2O/D2O buffers of a class II bacterial ent‐copalyl diphosphate synthase. Mass spectrometry determination of the extent of deuterium incorporation in the bicyclic product, reminiscent of initial carbocation formation by protonation, resulted in a large kinetic isotope effect of up to seven. Kinetic analysis at different temperatures confirmed that the isotope effect was independent of temperature, which is consistent with hydrogen tunneling.

Concerning the Role of Supercritical Carbon Dioxide in SN 1 Reactions.

A series of SN 1-type reactions has been studied under various conditions to clarify the role of supercritical carbon dioxide (scCO2 ) as reaction medium for this kind of transformations. The application of scCO2 did not result in higher yields in any of the experiments in comparison to those under neat conditions or in the presence of other inert compressed gases. High-pressure UV/Vis spectroscopic measurements were carried out to quantify the degree of carbocation formation of a highly SN 1-active alkyl halide as a function of the applied solvent. No measureable concentration of carbocations could be detected in scCO2 , just like in other low polarity solvents. Taken together, these results do not support the previously claimed activating effect via enhanced SN 1 ionization due to the quadrupolar moment of the supercritical fluid.

Crystal structure and enantioselectivity of terpene cyclization in SAM-dependent methyltransferase TleD.

TleD is a SAM (S-adenosyl-l-methionine)-dependent methyltransferase and acts as one of the key enzymes in the teleocidin B biosynthesis pathway. Besides methyl transferring, TleD also rearranges the geranyl and indole moieties of the precursor to form a six-membered ring. Moreover, it does not show homologies with any known terpenoid cyclases. In order to elucidate how such a remarkable reaction could be achieved, we determined the complex crystal structures of TleD and the cofactor analogue S-adenosyl-l-homocysteine with or without the substrate teleocidin A1. A domain-swapped pattern via an additional N-terminal α-helix is observed in TleD hexamers. Structural comparison and alignment shows that this additional N-terminal α-helix is the common feature of SAM methyltransferase-like cyclases TleD and SpnF. The residue Tyr21 anchors the additional N-terminal α-helix to a 'core SAM-MT fold' and is a key residue for catalytic activity. Molecular dynamics simulation results suggest that the dihedral angle C23-C24-C25-C26 of teleocidin A1 is preferred to 60-90° in the TleD and substrate complex structure, which tend to adopt a Re-face stereocenter at C25 position after reaction and is according to in vitro enzyme reaction experiments. Our results also demonstrate that methyl transfer can be a new chemical strategy for carbocation formation in the terpene cyclization, which is the key initial step.

Coke formation on the surface of Ni/HZSM-5 and Ni-Cu/HZSM-5 catalysts during bio-oil hydrodeoxygenation

Deactivation of zeolite catalysts due to coke deposition is a pronounced challenge in the hydrodeoxygenation (HDO) of bio-oil. This paper reports on the mechanism of coke formation and catalyst regeneration for two catalysts (Ni/HZSM-5, Ni-Cu/HZSM-5). FT-IR, XPS and Raman spectroscopy characterizations indicate that catalyst deactivation can be divided into three main stages: (1) Lewis acid sites in HZSM-5 support are rapidly covered by oxygenated hydrocarbons. The Brønsted acid sites of HZSM-5 donate protons to oxygenates, leading to the formation of carbocations - precursors of soluble coke on the catalyst surfaces. (2) Soluble coke is then stacked to form disordered filament-like carbon strands that are similar to carbon nanotubes or graphite-like structures. (3) Filament-like carbon evolves into graphite carbon. At the same HDO temperature, more graphite particles are found on the Ni/HZSM-5 catalyst than on the Ni-Cu/HZSM-5 catalyst, indicating higher resistance for the coke formation for Ni-Cu/HZSM-5 catalyst.

Single Molecule Nanospectroscopy Visualizes Proton-Transfer Processes within a Zeolite Crystal.

Visualizing proton-transfer processes at the nanoscale is essential for understanding the reactivity of zeolite-based catalyst materials. In this work, the Brønsted-acid-catalyzed oligomerization of styrene derivatives was used for the first time as a single molecule probe reaction to study the reactivity of individual zeolite H-ZSM-5 crystals in different zeolite framework, reactant and solvent environments. This was accomplished via the formation of distinct dimeric and trimeric fluorescent carbocations, characterized by their different photostability, as detected by single molecule fluorescence microscopy. The oligomerization kinetics turned out to be very sensitive to the reaction conditions and the presence of the local structural defects in zeolite H-ZSM-5 crystals. The remarkably photostable trimeric carbocations were found to be formed predominantly near defect-rich crystalline regions. This spectroscopic marker offers clear prospects for nanoscale quality control of zeolite-based materials. Interestingly, replacing n-heptane with 1-butanol as a solvent led to a reactivity decrease of several orders and shorter survival times of fluorescent products due to the strong chemisorption of 1-butanol onto the Brønsted acid sites. A similar effect was achieved by changing the electrophilic character of the para-substituent of the styrene moiety. Based on the measured turnover rates we have established a quantitative, single turnover approach to evaluate substituent and solvent effects on the reactivity of individual zeolite H-ZSM-5 crystals.

Decarboxylation Facilitated by Carbocation Formation and Rearrangement during Steam Distillation of Vetiver Oil.

Density functional theory (DFT) calculations are used to probe the validity of mechanistic proposals for the conversion of isozizanoic acid to 12-norisoziza-5-ene, a reaction that occurs during steam distillation of vetiver oil. While this conversion corresponds overall to a simple decarboxylation, a multistep mechanism involving carbocation intermediates is supported by the computational results.

A novel chemical technique for compatibility of ethylene-propylene-diene monomer rubber and styrene-butadiene rubber in their blends

The market for commercial polymer blends has grown steadily. A good blend should have strong interphases between different parts of the constituted polymers. Lack of strong interphases is a classical problem of the blend industry. Ethylene-propylene-diene monomer rubber (EPDM)/styrene-butadiene rubber (SBR) blends have a very good aging resistance and good compression sets. However, these rubbers are partially miscible. To improve the miscibility of EPDM and SBR in their blends, a Lewis acid, AlCl3, was used to form EPDM–g–SBR copolymer through Friedel–Crafts reactions. The existence of covalent bonds between EPDM and SBR macromolecules was studied by the cure traces of the blends, that is, ΔTorque, Fourier transform infrared spectrums, differential scanning calorimetry (DSC) heat flow curves, thermogravimetric analysis curves, and scanning electron (SEM) micrographs. Subsequently, several blends with EPDM/SBR ratio of 40/60 and with various AlCl3 amounts were prepared and after curing, their mechanical properties were measured and compared. The results showed covalent bonds formed between SBR–EPDM and SBR–SBR macromolecules. An exothermic change in heat flow in the DSC curve was observed around 111.28°C, which can be attributed to the formation of carbocations in Friedel–Crafts reactions. Adding 2 phr AlCl3 had an efficient effect on EPDM–SBR and or SBR–SBR linkages. The mechanical properties of the cured blends, that is, tensile strength were lower when compared with corresponding values for prepared compound with SBR. Excellent compatibility between the two polymers and strong interphases were observed in SEM micrograph of the cured blend with 1 phr AlCl3.

Carbocations Confined in a Thiatriazuliporphyrin Frame.

In the search for tricarbaporphyrinoids, a three-component acid-catalyzed condensation of azulene, 2,5-bis[(p-tolyl)hydroxymethyl]thiophene, and an aryl aldehyde has been elaborated, affording the appropriate thiatriazuliporphyrinogens. The subsequent oxidation yielded a rare example of a macrocyclic organic tetracation, which can be readily and reversibly converted into macrocyclic tri- and dicarbocations by addition of one or two hydroxides bound at the meso position(s). Further insight into the influence of carbocation formation on the geometry, electronic structure, and magnetic manifestation in (1) H NMR spectroscopy has been obtained by using density functional theory calculations. The charge distribution was evaluated by mapping electron density surfaces with electrostatic potential (ESP).

The effects of an ionic liquid on unimolecular substitution processes: the importance of the extent of transition state solvation.

The reaction of bromodiphenylmethane and 3-chloropyridine, which proceeds concurrently through both unimolecular and bimolecular mechanisms, was examined in mixtures of acetonitrile and an ionic liquid. As predicted, the bimolecular rate constant (k2) gradually increased as the amount of ionic liquid in the reaction mixture increased, as a result of a minor enthalpic cost offset by a more significant entropic benefit. Addition of an ionic liquid had a substantial effect on the unimolecular rate constant (k1) of the reaction, with at least a 5-fold rate enhancement relative to acetonitrile, which was found to be due to a significant decrease in the enthalpy of activation, partially offset by the associated decrease in the entropy of activation. This is in contrast to the effects seen previously for aliphatic carbocation formation, where the entropic cost dominated reaction outcome. This change is attributed to a lessened ionic liquid-transition state interaction, as the incipient charges in the transition state were delocalized across the neighbouring π systems. By varying the mole fraction of ionic liquid in the reaction mixture the ratio between k1 and k2 could be altered, highlighting the potential to use ionic liquids to control which pathway a reaction proceeds through.

Synthesis and some properties of 2H-benzimidazole 1,3-dioxides

The synthesis of novel 2H-benzimidazole 1,3-dioxides on the basis of benzofuroxans interaction with alcohols in acids is described. The formation of a stable secondary carbocation from alcohol is necessary for formation of 2H-benzimidazole 1,3-dioxide while substituents in benzofuroxans don't prevent the reaction. Under heating 2H-benzimidazole 1,3-dioxides are rearranged to 3H-[2,1,4]benzoxadiazine 4-oxides whose stability depends on substituents in the aromatic ring. Under irradiation oxadiazines are converted back to 2H-benzimidazole 1,3-dioxides.

Analysis of diarylmethylamine compounds using electrospray mass spectrometry: formation mechanisms of radical ions and dehydro cations.

A series of diarylmethylamine compounds were analyzed using electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). [M](+)˙ and [M - H](+) were both observed, but showed different abundances. A possible mechanism for the formation of [M](+)˙ and [M - H](+) was proposed to explicate the rule for the ratio change of I([M](+)˙)/I([M-H](+)). The [M](+)˙ has two structures, which can interconvert into each other in the gas phase. The substituted groups on the benzene rings play a crucial role in the transfer between the two structures. Electron withdrawing groups can prevent the formation of carbocations, thus nitro-containing diarylmethylamines remained mainly as structure I and were detected as [M](+)˙. On the contrary, electron donating groups help to stabilize carbocations. This makes structure I transfer to structure II, and structure II prefers to further generate [M - H](+) by loss of an H radical. Nuclear magnetic resonance and D-labelled MS experiments indicate that the 1-C-H bond has strong activity.

A mechanism-based inactivator of glycoside hydrolases involving formation of a transient non-classical carbocation.

The design of mechanism-based enzyme inactivators to generate chemical probes for biological research is an important challenge in carbohydrate chemistry. Here we describe the synthesis and biological evaluation of a novel carbocyclic mechanism-based inactivator of galactosidases (glycoside hydrolase families 27 and 36). Upon catalysis of this unnatural substrate, a transient non-classical carbocation forms within the enzyme active site. We show that the inactivation event, which proceeds via a bicyclobutonium ion intermediate, leads to a single alkylation event that occurs on the enzymatic nucleophile, an aspartic acid residue in this case. We also show that the catalytic proficiencies for enzymatic hydrolysis of substrates and inactivation by our bicyclo[4.1.0]heptyl analogue of galactose differ by only a factor of 20. This inactivator has the potential for further development as a useful biological research tool for both basic research and biotechnological applications.

Origin of product selectivity in a prenyl transfer reaction from the same intermediate: exploration of multiple FtmPT1-catalyzed prenyl transfer pathways.

FtmPT1 is a fungal indole prenyltransferase that catalyzes the reaction of tryptophan derivatives with dimethylallyl pyrophosphate to form various biologically active compounds. Herein, we describe detailed studies of FtmPT1 catalysis involving dimethylallyl pyrophosphate and Brevianamide F following the native pathway (yielding Tryprostatin B) and an alternate pathway observed in the Gly115Thr mutant of FtmPT1 yielding a novel cyclized product. Importantly, these two products arise from the same intermediate state, meaning that a step other than the cleavage of the dimethylallyl pyrophosphate (DMAPP; C–O) bond is differentiating between the two product reaction channels. From detailed potential of mean force (PMF) and two-dimensional PMF analyses, we conclude that the rate-limiting step is the cleavage of the C–O bond in DMAPP, while the deprotonation/cyclization step determines the final product distribution. Hence, in the case of FtmPT1, the optimization of the necessary catalytic machinery guides the generation of the final product after formation of the intermediate carbocation.

ChemInform Abstract: Copper Triflate: An Efficient Catalyst for Direct Conversion of Secondary Alcohols into Azides.

A simple, practical, and efficient strategy has been demonstrated for the direct synthesis of organic azides from alcohols using azidotrimethylsilane (TMSN3) as azide source in the presence of copper(II) triflate [Cu(OTf)2]. A variety of alcohols was converted into the corresponding azides in good to excellent yields. The formation of an intermediate carbocation was confirmed by the synthesis of bis(diphenylmethyl) ether.

Induced‐Fit Mechanism in Class I Terpene Cyclases

We present crystallographic and functional data of selina-4(15),7(11)-diene synthase (SdS) from Streptomyces pristinaespiralis in its open and closed (ligand-bound) conformation. We could identify an induced-fit mechanism by elucidating a rearrangement of the G1/2 helix-break motif upon substrate binding. This rearrangement highlights a novel effector triad comprising the pyrophosphate sensor Arg178, the linker Asp181, and the effector Gly182-O. This structural motif is strictly conserved in class I terpene cyclases from bacteria, fungi, and plants, including epi-isozizaene synthase (3KB9), aristolochene synthase (4KUX), bornyl diphosphate synthase (1N20), limonene synthase (2ONG), 5-epi-aristolochene synthase (5EAT), and taxa-4(5),11(12)-diene synthase (3P5R). An elaborate structure-based mutagenesis in combination with analysis of the distinct product spectra confirmed the mechanistic models of carbocation formation and stabilization in SdS.

Copper Triflate: An Efficient Catalyst for Direct Conversion of Secondary Alcohols into Azides

A simple, practical, and efficient strategy has been demonstrated for the direct synthesis of organic azides from alcohols using azidotrimethylsilane (TMSN₃) as azide source in the presence of copper(II) triflate [Cu(OTf)₂]. A variety of alcohols was converted into the corresponding azides in good to excellent yields. The formation of an intermediate carbocation was confirmed by the synthesis of bis(diphenylmethyl) ether.