Isomeric Intermediates Research Articles

Trivalent Heteroglycoclusters as Focal Point Pseudoenantiomers: Synthesis and Preliminary Biological Evaluation

AbstractWe describe the synthesis of the first heteroglycoclusters featuring three distinct carbohydrate ligands. The obtained pair of stereoisomeric glycoclusters were named “focal point enantiomers”, as the configuration of the focal point is the only varying stereogenic element in these molecules. The first pair of such diastereomeric heteroglycoclusters was accessible by an efficient sequence of protection and sequential glycosylation steps utilizing a mannosyl, a N‐acetylglucosaminyl, and a galactosyl donor, respectively, which was applied to a prototype azido‐functionalized tris(hydroxymethyl)aminomethane (TRIS) scaffold molecule. The stereoisomers could be distinguished based on an X‐ray structure of one of the isomeric key intermediates. As previously shown with divalent counterparts, such heterotrivalent cluster glycosides are useful tools for studying the fine‐tuning of carbohydrate recognition. The azido functional group at the focal point of the synthetic scaffold molecule was employed in a conjugation reaction with a linker for further immobilization on a gold surface in order to fabricate glyco‐SAMs (self‐assembled monolayers). A preliminary biological evaluation of the focal point enantiomers was performed in solution using the well‐known model lectin Concanavalin A and the important bacterial lectin FimH.

Consecutive Trifluoromethylation of C88(7) Fullerene: A Theoretical Study

AbstractThe trifluoromethylation of C88(7) fullerene has been systematically studied using an energy‐controlled consecutive CF3 addition approach. The thermodynamically favored C88(7)(CF3)2n isomers with 2n = 2–20 were predicted at the DFT B3LYP‐D3BJ/6–311G* level of theory for the first time, in harmony with the two experimentally characterized isomers C88(7)(CF3)12/16. It was found that these stable isomers are formed mainly by 1,4‐additions of CF3 groups, and meanwhile, there are a few stable isomers with isolated CF3 groups for 2n ≤ 12, with ortho addition for 2n > 12, and with triple‐hexagon‐junction addition for the highest degree of trifluoromethylation (2n ≥ 18). The addition patterns of CF3 groups were discussed in terms of the local structural motif of the pristine cage and the formation of stabilizing substructures of local aromaticity. The possible trifluoromethylation pathways of C88(7) were proposed on the basis of the relative Gibbs free energies. The results show that almost all the intermediate isomers for the thermodynamically most stable isomers of C88(7)(CF3)2n possess low relative Gibbs free energies (below 14 kJ·mol−1). Moreover, the hardness, chemical potential, electrophilicity index, electron affinity, HOMO and LUMO energies, and HOMO–LUMO gaps of the thermodynamically most stable C88(7)(CF3)2n isomers were also calculated.

Isomeric Speciation of Bisbenzoxazine Intermediates by Ion Spectroscopy and Ion Mobility Mass Spectrometry.

Bisbenzoxazines (BisBz) are a relevant model for the diverse bifunctional benzoxazines that are used to increase the polybenzoxazines cross-linking extensions and modulate the final resin properties for various usages. The presence of side products and intermediates during monomer formation can influence the resin characteristics by inducing chain termination and ramifications, affecting the polymerization and cure processes. This work investigated the diverse isomeric intermediates and side products that are present during the BisBz formation from bisphenol A, aniline, and formaldehyde by ion mobility coupled to tandem mass spectrometry (MS/MS) and ion spectroscopy techniques. The species detected in this work suggest that these multifunctional phenols open diverse concurrent reaction pathways based on two main reactive steps: (i) the imine/iminium phenol attack to form a phenylamino intermediate and (ii) the formaldehyde attack followed by dehydration to form the oxazine ring. The species observed also support previous studies of the benzoxazine formation mechanism and showcase the application of advanced analytical techniques in studying complex chemical systems.

Unexpected E-to-Z Isomerizations during the Negishi-Type Homocoupling of E-Iodoalkenes.

The direct insertion of Zn into olefin-halide bonds is a challenge. When (E)-alkenyl iodides were treated with a very large excess of Zn nanoparticles, in the presence of Pd(PPh3)4, the dimerization was observed but, unexpectedly, yielding mainly Z,E-1,3-dienes. This apparently contrathermodynamic E-to-Z isomerization of organometallic intermediates is predicted to be general and is explained with the aid of DFT [principally M06/6-311+G(d,p)], MP2, and CCSD(T) calculations.

Tetraaryl-3H-Azepines: KOBut/DMSO-Catalyzed Assembly from Diaryldiynes and N-Benzylaldimines.

Di(het)aryldiynes smoothly react with N-benzylaldimines in a [4 + 3] cycloaddition manner under the action of the KOBut/DMSO system (60 °C, 30 min) to afford pharmaceutically relevant tetra(het)arylsubstituted 3H-azepines in up to 71% yield. The process involves the addition of azaallyl anions to one of the triple bonds of diynes followed by prototropic isomerization and cyclization of anionic intermediates with participation of the second triple bond. The cascade mechanism is consistent with quantum-chemical analysis (B2PLYP-D3/6-311+G**//B3LYP-D3/6-31+G* + PCM).

Intrinsic Molecular Mechanisms of Transformation between Isomeric Intermediates Formed at Different Stages of Cysteine-Xylose Maillard Reaction Model through Dehydration.

2-Threityl-thiazolidine-4-carboxylic acid (TTCA) and Amadori rearrangement product (ARP), the isomeric intermediates derived from the cysteine-xylose (Cys-Xyl) Maillard reaction model, possessed the ability to produce similar flavor profile during the thermal process, but the flavor formation or browning rate of heated TTCA was significantly lower than that of ARP. Macroscopically, the yield of TTCA reached the maximum when the moisture content of the reaction system just dropped to nearly 0% during the thermal reaction-vacuum dehydration process. During the subsequent dynamic intramolecular dehydration process, the reaction remained at an early stage of the Maillard reaction, and TTCA was the main intermediate. Thereinto, the water activity of the samples decreased with the increased dehydration time. From a molecular perspective, the dissipation of free water promoted the conversion of combined water to immobilized water and free water, increasing the intramolecular dehydration. Instantaneous high-temperature dehydration during the spray drying process revealed a higher efficiency than the thermal reaction-vacuum dehydration process, which facilitated the specific conversion of substrates to intermediates (TTCA, ARP). The loss of free water and immobilized water was a key driving force for the direct formation of TTCA/ARP, regulating the formation stages of MRIs. The increase of the inlet air temperature could alter the ratio of TTCA and ARP at the equilibrium state.

Molecular Structures and Vibrational Spectra of trans- and cis-Polyacetylene and Their Oligoenes Revisited Using Density Functional Theory Calculations.

Polyacetylene, the most representative synthetic conducting polymer, has attracted much attention because it exhibits high conductivity upon doping. In this paper, molecular structures, electronic excitation energies, and Raman and infrared spectra were calculated using density functional theory for trans- and cis-oligoenes with various chain lengths up to the number of C═C bonds (n) of 100 and trans- and cis-polyacetylenes under one-dimensional periodic boundary condition. The harmonic vibrational frequencies obtained at the B3LYP/6-311G(d,p) level were scaled by the scaling factors determined with respect to the anharmonic vibrational frequencies using the B2PLYP method, in which the coefficients of the functional were optimized for trans-oligoenes. The calculated infrared and Raman frequencies reproduce reasonably well the observed frequencies for trans- and cis-polyacetylene. Based on the chain-length dependence of the calculated Raman spectra of trans-oligoenes, we proposed the possibility of longer conjugated trans-segments observed in the resonance Raman spectra of trans-polyacetylene excited at longer wavelengths of 647.1 and 1064 nm. We also elucidated the origin of the excitation-wavelength dependence of the resonance Raman spectra of trans-polyacetylene and the structure of isomerization intermediates from cis-form to trans-form. In addition, the previous assignments of Raman and infrared spectra of trans- and cis-polyacetylene were reexamined in the present study based on the chain-length dependence of the spectra.

Isotope Effects in the Zundel-Eigen Isomerization of H+(H2O)6.

The isomerization pathway between the energetically low-lying Zundel and Eigen isomers of the protonated water hexamer was investigated using high-level ab initio calculations including a treatment of zero-point corrections. On the basis of these calculations, the Zundel-Eigen isomerization was found to proceed through a stable intermediate isomer, which consists of a four-membered ring with two single acceptor water molecules. The inclusion of vibrational zero-point energy is shown to be important for accurately establishing the relative energies of the three relevant isomers involved in the Zundel-Eigen isomerization. Diffusion Monte Carlo calculations including anharmonic vibrational effects show that all three isomers of H+(H2O)6 and D+(D2O)6 have well-defined structures. The energetic ordering of the three isomers changes upon deuteration. The implications of these results for the vibrational spectra of H+(H2O)6 and D+(D2O)6 are also discussed.

An experimental and theoretical investigation of the N(2D) + C6H6 (benzene) reaction with implications for the photochemical models of Titan.

We report on a combined experimental and theoretical investigation of the N(2D) + C6H6 (benzene) reaction, which is of relevance in the aromatic chemistry of the atmosphere of Titan. Experimentally, the reaction was studied (i) under single-collision conditions by the crossed molecular beams (CMB) scattering method with mass spectrometric detection and time-of-flight analysis at the collision energy (Ec) of 31.8 kJ mol-1 to determine the primary products, their branching fractions (BFs), and the reaction micromechanism, and (ii) in a continuous supersonic flow reactor to determine the rate constant as a function of temperature from 50 K to 296 K. Theoretically, electronic structure calculations of the doublet C6H6N potential energy surface (PES) were performed to assist the interpretation of the experimental results and characterize the overall reaction mechanism. The reaction is found to proceed via barrierless addition of N(2D) to the aromatic ring of C6H6, followed by formation of several cyclic (five-, six-, and seven-membered ring) and linear isomeric C6H6N intermediates that can undergo unimolecular decomposition to bimolecular products. Statistical estimates of product BFs on the theoretical PES were carried out under the conditions of the CMB experiments and at the temperatures relevant for Titan's atmosphere. In all conditions the ring-contraction channel leading to C5H5 (cyclopentadienyl) + HCN is dominant, while minor contributions come from the channels leading to o-C6H5N (o-N-cycloheptatriene radical) + H, C4H4N (pyrrolyl) + C2H2 (acetylene), C5H5CN (cyano-cyclopentadiene) + H, and p-C6H5N + H. Rate constants (which are close to the gas kinetic limit at all temperatures, with the recommended value of 2.19 ± 0.30 × 10-10 cm3 s-1 over the 50-296 K range) and BFs have been used in a photochemical model of Titan's atmosphere to simulate the effect of the title reaction on the species abundances as a function of the altitude.

Reaction N(2D) + CH2CCH2 (Allene): An Experimental and Theoretical Investigation and Implications for the Photochemical Models of Titan.

We report on a combined experimental and theoretical investigation of the N(2D) + CH2CCH2 (allene) reaction of relevance in the atmospheric chemistry of Titan. Experimentally, the reaction was investigated (i) under single-collision conditions by the crossed molecular beams (CMB) scattering method with mass spectrometric detection and time-of-flight analysis at the collision energy (Ec) of 33 kJ/mol to determine the primary products and the reaction micromechanism and (ii) in a continuous supersonic flow reactor to determine the rate constant as a function of temperature from 50 to 296 K. Theoretically, electronic structure calculations of the doublet C3H4N potential energy surface (PES) were performed to assist the interpretation of the experimental results and characterize the overall reaction mechanism. The reaction is found to proceed via barrierless addition of N(2D) to one of the two equivalent carbon–carbon double bonds of CH2CCH2, followed by the formation of several cyclic and linear isomeric C3H4N intermediates that can undergo unimolecular decomposition to bimolecular products with elimination of H, CH3, HCN, HNC, and CN. The kinetic experiments confirm the barrierless nature of the reaction through the measurement of rate constants close to the gas-kinetic rate at all temperatures. Statistical estimates of product branching fractions (BFs) on the theoretical PES were carried out under the conditions of the CMB experiments at room temperature and at temperatures (94 and 175 K) relevant for Titan. Up to 14 competing product channels were statistically predicted with the main ones at Ec = 33 kJ/mol being formation of cyclic-CH2C(N)CH + H (BF = 87.0%) followed by CHCCHNH + H (BF = 10.5%) and CH2CCNH + H (BF = 1.4%) the other 11 possible channels being negligible (BFs ranging from 0 to 0.5%). BFs under the other conditions are essentially unchanged. Experimental dynamical information could only be obtained on the overall H-displacement channel, while other possible channels could not be confirmed within the sensitivity of the method. This is also in line with theoretical predictions as the other possible channels are predicted to be negligible, including the HCN/HNC + C2H3 (vinyl) channels (overall BF < 1%). The dynamics and product distributions are dramatically different with respect to those observed in the isomeric reaction N(2D) + CH3CCH (propyne), where at a similar Ec the main product channels are CH2NH (methanimine) + C2H (BF = 41%), c-C(N)CH + CH3 (BF = 32%), and CH2CHCN (vinyl cyanide) + H (BF = 12%). Rate coefficients (the recommended value is 1.7 (±0.2) × 10–10 cm3 s–1 over the 50–300 K range) and BFs have been used in a photochemical model of Titan’s atmosphere to simulate the effect of the title reaction on the species abundance (including any new products formed) as a function of the altitude.

Charge-Separated Reactive Intermediates from the UV Photodissociation of Chlorobenzene in Solution.

Although ultraviolet (UV)-induced photochemical cleavage of carbon–halogen bonds in gaseous halocarbons is mostly homolytic, the photolysis of chlorobenzene in solution has been proposed to produce a phenyl cation, c-C6H5+, which is a highly reactive intermediate of potential use in chemical synthesis and N2 activation. Any evidence for such a route to phenyl cations is indirect, with uncertainty remaining about the possible mechanism. Here, ultrafast transient absorption spectroscopy of UV-excited (λ = 240 and 270 nm) chlorobenzene solutions in fluorinated (perfluorohexane) and protic (ethanol and 2,2,2-trifluoroethanol) solvents reveals a broad electronic absorption band centered at 540 nm that is assigned to an isomer of chlorobenzene with both charge-separated and triplet-spin carbene character. This spectroscopic feature is weaker, or absent, when experiments are conducted in cyclohexane. The intermediate isomer of chlorobenzene has a solvent-dependent lifetime of 30–110 ps, determined by reaction with the solvent or quenching to a lower-lying singlet state. Evidence is presented for dissociation to ortho-benzyne, but the intermediate could also be a precursor to phenyl cation formation.

Theoretical Investigation of Dissociation versus Intramolecular Rearrangements in Aminohydroxymethylene.

Aminohydroxymethylene (H2N-C̈-OH) is the simplest aminooxycarbene which is a heteroatom stabilized carbene. This highly reactive molecule was prepared in an Ar matrix in a recent experimental work. Unimolecular reactivity of this astrochemically important molecule was investigated and only fragmentations were identified contrary to the observations of both fragmentations and intramolecular rearrangements in other hydroxycarbenes. These rearrangement reactions form the corresponding imine and carbonyl compounds. In the present work, direct chemical dynamics simulations of unimolecular chemistry of aminohydroxymethylene were performed in the gas phase to study atomic level dissociation mechanisms. Classical trajectories were generated on-the-fly using potentials and gradients computed at the density functional B3LYP/6-31+G* level of electronic structure theory. Simulation results showed that intramolecular rearrangements accompany fragmentations during the unimolecular decay process of aminohydroxymethylene. However, the average lifetime of the intermediate isomers were found to be only few picoseconds which might not have been long enough for detection in the experiments.

Mechanism and the Origins of Periselectivity in Cycloaddition Reactions of Benzyne with Dienes.

Density functional theory calculations have been used to explore the reaction mechanism of (4 + 2) and (2 + 2) cycloadditions of benzyne with classical dienes. The results indicate the following: (1) (4 + 2) products arise via concerted pathways, (2) (2 + 2) products arise via stepwise pathways with diradical intermediates, and (3) these diradical intermediates are formed via isomerization of carbene intermediates. The origins of periselectivity in these reactions are analyzed using distortion/interaction analysis for the key steps, and they indicate that the tiny distortion in the very early [4 + 2] transition structure, coupled with an entropic favorability, controls selective (4 + 2) cycloaddition.

Making the second generation of molecular motors operate unidirectionally in response to electricity

Electricity is an attractive energy input to operate molecular motors. We found that anionization using constant potential could make the 2nd generation molecular motors operate under ground state unidirectionally, persistently, and free from ultraviolet light. In this approach, the original energetically uphill step with large energy barrier driven by ultraviolet could be replaced by a combination of an anionization step followed by an energetically downhill anionic isomerization and a neutralization step. Anionization decreases the energy barrier of the first isomerization step significantly, while the barrier of the second isomerization step still keeps high level, which ensures nearly 100% perfect unidirectionality kinetically. The free energy of the anionic intermediate isomer is lower enough than that of the original isomer, which makes the isomerization could be driven thermodynamically and ensures the nearly 100% perfect unidirectionality. We hope that our investigations could provide a new strategy for constructing electronic stimuli-responsive nanosystems based on the 2nd generation molecular motors.

An examination of the reaction pathways of XO + O → X + O2 (X = Br and I)

Kinetics and mechanism of potentially important atmospheric ozone depletion reactions XO + O → X + O2 (X = Br and I) have been explored at the ab initio level. Several minimum energy geometries and transition states are identified at the MP2 level using correlation consistent triple zeta and effective core potential basis sets and energetics are obtained at the QCISD(T)//MP2 level of theory. Possible reaction pathways are discussed on the basis of IRC calculations and changes of geometries along the reaction paths. A direct reaction mechanism as well as reaction path via transition states and equilibrium geometries are identified. For both the reactions, early transition states have been detected just after the reactions start. In case of BrO + O reaction, we obtained a transition state of Br.OO type before the product formation, whereas in case of IO + O reaction, an equilibrium geometry of I.OO type has been detected leading to the product formation. Similar to I.OO, for ClO + O reaction an equilibrium geometry of Cl.OO type was reported in literature for product formation. This anomaly for TS-Br.OO may be due the artifact of MP2 optimization method. A multi-reference approach is expected to reveal the correct picture. A detailed dynamical study of this transition state may lead to clear bond-breaking and bond-forming information, which may be helpful to predict the true reaction pathway. Heats of reaction are found to be consistent with experimental data. Bond dissociation energies of the ground state intermediate isomers to various dissociation asymptotes are also reported. This is the first theoretical report for the possible reaction pathways and may be served as a reference for future investigation using higher methodology.

Efficient and stable SiO2-encapsulated NiPt/HY catalyst for catalytic cracking of β-O-4 linkage compound

Development of highly active and stable catalyst for C–O bonds cracking is important in biomass conversion, in this work, we report a SiO2-encapsulated NiPt/HY core-shell catalyst for phenethoxybenzene (PEB) catalytic cracking. The as-grown silica shell with defined pores serves as a ‘storage’ to enhance local concentration of PEB and intermediate isomers and promotes catalytic cracking on NiPt/HY core. With the increase of silica shell thickness from 0 to 40 nm, PEB reaction rate has increased more than five times, and the major cracking product selectivity is raised to above 90%, which is attributed to the continuous conversion of PEB isomers within the shell. This designed structure endows the NiPt/HY@SiO2 with a high activity and no obvious deactivation in PEB cracking to corresponding phenol and aromatics. The outstanding performance benefit from the enrichment effect on the unique core-shell structure, as well as the moderate acidity originated from silica regulation. This work can be extended to the modulation of microenvironment to promote the catalytic behavior of core-shell catalysts.

Stability of Terpenoid-Derived Secondary Ozonides in Aqueous Organic Media

1,2,4-Trioxolanes, known as secondary ozonides (SOZs), are key products of ozonolysis of biogenic terpenoids. Functionalized terpenoid-derived SOZs are readily taken up into atmospheric aerosols; however, their condensed-phase fates remain unknown. Here, we report the results of a time-dependent mass spectrometric investigation into the liquid-phase fates of C10 and C13 SOZs synthesized by ozonolysis of a C10 monoterpene alcohol (α-terpineol) in water:acetone (1:1 = vol:vol) mixtures. Isomerization of Criegee intermediates and bimolecular reaction of Criegee intermediates with acetone produced C10 and C13 SOZs, respectively, which were detected as their Na+-adducts by positive-ion electrospray mass spectrometry. Use of CD3COCD3, D2O, and H218O solvents enabled identification of three types of C13 SOZs (aldehyde, ketone, and lactol) and other products. These SOZs were surprisingly stable in water:acetone (1:1) mixtures at T = 298 K, with some persisting for at least a week. Theoretical calculations supported the high stability of the lactol-type C13 SOZ formed from the aldehyde-type C13 SOZ via intramolecular rearrangement. The present results suggest that terpenoid-derived SOZs can persist in atmospheric condensed phases, potentially until they are delivered to the epithelial lining fluid of the pulmonary alveoli via inhaled particulate matter, where they may exert hitherto unrecognized adverse health effects.

Selective dehydra-decyclization of cyclic ethers to conjugated dienes over zirconia

ZrO2 provides high selectivity (>90%) to conjugated pentadienes through the dehydra-decyclization of C-5 cyclic ethers, even at high conversions. 1,3-Pentadiene was the major product in both reaction of 2-methyltetrahydrofuran and tetrahydropyran over ZrO2. The reaction of 3-methyltetrahydrofuran produced nearly stoichiometric amounts of isoprene. Other catalysts, including TiO2, γ-Al2O3, and H-ZSM-5, were generally much less selective and produced a mixture of diene isomers. A combination of TPD and steady-state measurements revealed that both piperylenes are exclusively produced through primary catalytic pathways from 2-methyltetrahydrofuran, avoiding any isomerization once formed. First-principle calculations on ZrO2 imply the presence of an energetically favored, surface isomerization of ring-opened intermediates to conjugated alkenolates that selectively dehydrate to conjugated dienes, providing high selectivity to the desired products. The stabilization of the conjugated alkenolate is key for understanding the ability of ZrO2 to selectively produce conjugated dienes from cyclic ethers, without the need for the thermo-limited diene isomerization.

Development of a [2 + 2]-Nitroso/Alkene Cycloaddition Using Sodium Tetrakis[3,5-bis(trifluoromethyl)phenyl]borate Catalyst: Controlled Chemoselectivity of Two Equilibrating Isomeric Intermediates.

Sodium tetrakis[3,5-bis(trifluoromethyl)-phenyl]borate (NaBArF) catalyzes the [2 + 2] cycloaddition of 1,4-disubstituted cyclopenta-1,3-dien-2-yl esters with nitrsobenzene in toluene, affording two isolable regioisomers of 6-oxa-7-azabicyclo[3.2.0] heptanes, which thermally rearrange into the same 4-aminocyclopent-1-en-3-ones. In the case of 4-substituted cyclopenta-1,3-dien-2-yl esters, their initial [2 + 2] cycloaddition intermediates undergo a rapid ring expansion to afford six-membered piperidone derivatives efficiently.

Efficient conversion of carbohydrates and biomass into furan compounds by chitin/Ag co-modified H3PW12O40 catalysts

The development of heterogeneously functional catalysts is of great significance in selective catalysis for biomass valorization. Herein, we report for the first time the applicability of chitin/Ag co-modified H3PW12O40 composites (Chx-AgPW) as catalysts for producing valuable furans from carbohydrates and biomass. The as-prepared Ch15-AgPW catalyst exhibited the best catalytic performance, due to the dual Brǿnsted-Lewis acidity and appropriate chitin content. When the amount of Ch15-AgPW catalyst was 0.25 mmol, an excellent 5-hydroxymethylfurfural (HMF) yield of 78.3% could be achieved at 150 °C for 3 h with nearly 100% glucose conversion in the H2O/MIBK (VH2O:MIBK = 4:6) solvent system. Furthermore, high-yield HMF could also be obtained from other carbohydrates such as fructose (85.3%), sucrose (72.3%), cellobiose (65.6%), starch (52.7%) and inulin (43.5%). Additionally, corn stover, rice straw and sugarcane bagasse under typical reaction conditions simultaneously produced furfural and HMF in yields of 64.6%–72.2% and 18.5%–25.6%, respectively. Combined with the characterization, mechanism study demonstrated that the surface functional groups in chitin were conductive to rapid absorption of the substrates; the Brǿnsted acid sites from heteropoly anion (H2[PW12O40]-) promoted the initial depolymerization of biomass and the final dehydration to furans; the introduction of Ag+ favored the isomerization of intermediates. After reaction finished, the Ch15-AgPW catalyst could be easily recovered by filtration and effectively reused at least eight cycles without substantial loss in catalytic activity. This work provides a novel strategy to synthesize stable heterogeneous catalysts with tunable acidity for producing bio-based fuels and chemicals from renewable resources.