Conformationally controlled (entropy effects), stereoselective vibrational quenching of singlet oxygen in the oxidative cleavage of oxazolidinone-functionalized enecarbamates through solvent and temperature variations

On photooxygenation (methylene blue as sensitizer) of E/Z enecarbamates, equipped with the oxazolidinone chiral auxiliary, the oxidative cleavage of the alkenyl functionality releases the enantiomerically enriched methyldesoxybenzoin (MDB) product. The extent (% ee) as well as the sense (R vs S) of the stereoselectivity in the MDB formation depends on the choice of the alkene configuration; the efficacy of stereocontrol may be tuned by appropriate solvent and temperature conditions. Highlighted is the finding that the formation of the preferred MDB enantiomer (R or S) depends for the E isomer on the chosen solvent and temperature, but not for the corresponding Z isomer. The activation parameters for the various solvents disclose that differential entropy effects (ΔΔS^‡) dominate the conformationally more flexible E diastereomers. As mechanistic rationale for this unprecedented conformationally imposed stereochemical behavior, we propose the competitive action of stereoselective vibrational quenching of the attacking singlet oxygen by the enecarbamate versus sterically controlled stereoselective oxidative cleavage of its double bond.     

Stereocontrol within confined spaces: enantioselective photooxidation of enecarbamates inside zeolite supercages

Dye-exchanged Y zeolite is shown to be an effective medium to control the stereoselectivity in the photooxygenation of chiral oxazolidinone-functionalized Z/E-1 enecarbamates. An enantioselectivity (ee) as high as 80% was observed in the methyldesoxybenzoin (MDB) product, obtained in the methylene-blue-exchanged NaY zeolite at room temperature. The efficacy of the asymmetric induction in the MDB product depends on the Z/E geometry of the alkene, the Z-isomer being more effective than the corresponding E-isomer. The stereoselectivity is rationalized in terms of conformational effects through cationic interactions between the zeolite and the substrate.     

A comparative mechanistic analysis of the stereoselectivity trends observed in the oxidation of chiral oxazolidinone-functionalized enecarbamates by singlet oxygen, ozone, and triazolinedione

The stereoselectivity in the reactions of the E/Z enecarbamates 1, equipped with the oxazolidinone chiral auxiliary, has been examined for singlet oxygen (¹O₂), ozone (O₃), and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) in a variety of solvents as a function of temperature. The oxidative cleavage of the alkenyl functionality by ¹O₂ and O₃ releases the enantiomerically enriched methyldesoxybenzoin (MDB) product. The extent (% ee) as well as the sense (R vs S) of the stereoselectivity in the MDB formation depends on the electronic nature of the oxidant. A high stereoselectivity, substantially dependent on solvent and temperature, is displayed for the reactions with ¹O₂, whereas the ground-state reactants O₃ and PTAD are rather unaffected by solvent and temperature variations. The present comparative analysis clearly substantiates our hypothesis of stereoselective vibrational quenching of the attacking ¹O₂, whereas O₃ and PTAD are only subject to steric impositions. The electronically excited ¹O₂ is sensitive to all three stereochemically relevant structural characteristics embodied in the chiral enecarbamates, namely the R/S configuration at the C₄ position of the oxazolidinone chiral auxiliary, the Z/E geometry of the ‘alkene’ functionality, and R/S configuration at the C_3′ position of the enecarbamate side chain.     

A supramolecular "ship in bottle" strategy for enantiomeric selectivity in geminate radical pair recombination

[reaction: see text] Reactions in which zeolites are modified with chiral inductors to serve as media for chiral induction are often limited by the propensity of both substrate and inductor to occupy the same supercage. Herein, we report a "ship in bottle" strategy utilizing the thermal decomposition of dioxetanes obtained from oxazolidinone-substituted enecarbamates for the enantioselective generation of methyl desoxybenzoin (MDB). Photoexcitation of the supramolecular geminate molecular pair results in enrichment of the opposite enantiomer of MDB.     

Control of chirality by cations in confined spaces: Photooxidation of enecarbamates inside zeolite supercages

On photooxygenation of the optically active Z/E enecarbamates 1 (X = i-Pr) and 2 (X = Me) equipped with the oxazolidinone chiral auxiliary in methylene-blue (MB)-incorporated, alkali-metal (M = Li, Na, K, Cs, Rb), exchanged Y-type zeolites (MY-MB), oxidative cleavage of the alkenyl functionality releases the enantiomerically enriched methyldesoxybenzoin (MDB) product. The extent (%ee) and/or the sense (R or S) of the stereoselectivity in the formation of the MDB product depends on the choice of the alkyl substiuent (i-Pr or Me) at the C-4 position of the oxazolidinone chiral auxiliary, the Z/E configuration of the alkene functionality in the enecarbamates, and the type of alkali metal in the zeolite. Most significantly-the highlight of this study-is the reversed sense (R or S) in the stereoselection when the photooxygenation is run in CDCl3 solution versus inside the MY-MB zeolite. As a mechanistic rationale for this novel stereochemical behavior, we propose the combined action of spatial confinement and metal-ion coordination (assessed by density-functional calculations) of the substrate within the zeolite supercage, both of which greatly reduce the freedom of the substrate and entropically manipulate the stereochemical outcome.     

Stereoselective E/Z photoisomerization of oxazolidinone functionalized enecarbamates: direct and triplet sensitized irradiation

Oxazolidinone-functionalized enecarbamates undergo diastereoselective E/Z photoisomerization upon direct and triplet sensitized irradiations with chiral/achiral sensitizers, showing that the enhanced product diastereoselectivity depends on the solvent and temperature.     

Stereochemical features of the physical and chemical interactions of singlet oxygen with enecarbamates

Oxazolidinone-substituted enecarbamates represent a mechanistically rich system for the study of stereoelectronic, steric, and conformational effects on stereoselectivity and mode selectivity in (1)O(2) [2 + 2] and ene reactions. Photooxygenation of these enecarbamates with (1)O(2) leads to diastereomerically pure dioxetanes that decompose to yield an oxazolidinone carbaldehyde and one of the two enantiomers of methyldesoxybenzoin in enantiomeric excess. Stereoselectivity originates at the allylic stereocenter, a result supported by quenching studies, computational analysis, and deuterium solvent isotope effects. [reaction: see text]     

Electrochemistry of cytochrome C in aqueous and mixed solvent solutions: thermodynamics, kinetics, and the effect of solvent dielectric constant

The solvent dielectric constant is considered an important factor in determining the redox potential of the heme-containing protein cytochrome c in solution. In this study, we investigate the electrochemical response of cytochrome c in aqueous/organic solvent mixtures (100% aqueous buffer, 30% acetonitrile, 40% dimethyl sulfoxide, and 50% methanol), reporting the redox potential (E degrees'), enthalpy, and entropy of reduction. The temperature dependence of the solvent dielectric constant (epsilon) was also measured. The results show that epsilon alone cannot regulate the E degrees' of cytochrome c in mixed solvent systems. The implications of the temperature dependence of epsilon on the validity of the thermodynamic data are also discussed. The effect of solvent and temperature on the electron-transfer rate constant, k(s), was determined in each solvent mixture. A substantial increase in the activation energy for electron transfer was observed in 40% DMSO.     

A New Method of Low Temperature Methanol Synthesis

Low temperature methanol synthesis is a promising technique for the practical methanol industry. New developments of a new kind of low temperature methanol synthesis were reviewed, including the effects of feed gas, reaction solvent, supercritical media and catalyst modification. The reaction mechanism and kinetics were also summarized primarily. Carbon dioxide played an important role in this new kind of low temperature methanol synthesis. It reacted with hydrogen adsorbed on catalyst surface to form HCOOM, an important reaction intermediate. Alcohol solvent in the low temperature methanol synthesis performed not only a media, but also a homogeneous catalyst. The reaction of the adsorbed formate species with alcohol on Cu/ZnO catalyst surface proceeded according to the Rideal mechanism rather than Langmuir–Hinshelwood mechanism to form alkyl formate. The formation of alkyl formate from alcohol solvent and hydrogenation of such an alkyl formate were the key steps in low temperature methanol synthesis reaction. These results provided new insights into low temperature methanol synthesis.     

Theoretical study of temperature and solvent dependence of the free-energy surface of the intramolecular electron-transfer based on the RISM-SCF theory: application to the 1,3-dinitrobenzene radical anion in acetonitrile and methanol

The free-energy surfaces along the intramolecular electron-transfer reaction path of the 1,3-dinitrobenzene radical anion in acetonitrile and methanol are investigated with the reference interaction site model self-consistent field theory. Although acetonitrile and methanol have similar values of the dielectric constant, the free-energy profiles are quite different. In the methanol solution, the charge is strongly localized on one of the nitrile substituents due to a strong hydrogen bond between 1,3-dinitrobenzene and the solvent, while the polarization is not so large in the case of acetonitrile. The temperature dependence of the reorganization energy, the coupling strength, and the activation barrier is evaluated in both acetonitrile and methanol. The reorganization energy and the activation barrier decrease with increasing temperature for both cases. The electronic coupling strength also shows a similar tendency in the temperature dependence; it increases with increasing temperature in both solvents but with different rates. The behavior is explained in terms of the strong polarization induced by the hydrogen bond between the solute and solvent in the methanol solution.     

Probing the stereoselectivity of the Heck arylation of endocyclic enecarbamates with diazonium salts. Concise syntheses of (2S,5R)-phenylproline methyl ester and Schramm's C-azanucleoside

[reaction: see text] The diastereoselectivity of the Heck arylation of several chiral, nonracemic, five-membered endocyclic enecarbamates with aryldiazonium tetrafluoroborates was evaluated. The cis selectivity observed for some enecarbamates bearing coordinating groups was explored in the concise synthesis of the (2S,5R)-(+)-phenylproline methyl ester, a scaffold for the nonpeptide cholecystokinin antagonist (+)-RP 66803, and in the synthesis of Schramm's potent antiprotozoan C-azanucleoside.     

Pressurized liquid extraction as a sample preparation method for the analysis of isoflavones in pulses

In this work, we describe a rapid and simple analytical method that exploits pressurized liquid extraction (PLE) and liquid chromatography with diode array detection for the determination of isoflavones in samples of Spanish pulses. Confirmation of the analytes present was performed using ion-trap mass spectrometry. To optimize the PLE extraction, variables such as the dispersing agent, type of solvent and sample amount, and the experimental parameters, such as temperature and the number of extraction cycles, were studied. Separation was carried out using a reverse-phase C18 with polar endcapping as the stationary phase and acetonitrile/water with 0.2?% of formic acid, under a gradient regime, as the mobile phase. Optimal extraction of formononetin and biochanin-A from chickpeas with PLE was achieved using Hydromatrix as a dispersant agent, methanol/water (50:50), a temperature of 90?°C, and three cycles. The same optimal conditions-except methanol/water (75:25)-for solvent extraction were obtained for the extraction of daidzin, genistin, and formononetin from lentils. Recoveries ranged from 97 to 110?%, and standard deviations lower than 20?% were obtained. The contents obtained for daidzin in lentils using the proposed method were not significantly different from those obtained using another official method of analysis.     

Optimization of microwave-assisted extraction for alizarin and purpurin in Rubiaceae plants and its comparison with conventional extraction methods

A simple and rapid microwave-assisted extraction (MAE) procedure was developed and optimized for two common color pigments, alizarin and purpurin, in various samples of Rubiaceae plants. Several variables that can potentially affect the extraction efficiency, namely temperature, methanol concentration in the extractant mixture, time, and solvent volume were optimized by means of a central composite design approach. The results suggest that temperature and methanol concentration in the solvent mixture are statistically the most significant factors. The separation and quantitative determination of the pigments was carried out in less than 6 min by a developed high-performance liquid chromatographic method with UV detection at 250 nm. Under optimum operating conditions, MAE showed significantly higher recoveries than those obtained by the conventional extraction methods (ultrasonic and reflux extraction), ranging from 84 to 94%. In addition, a drastic reduction of the extraction time (20 min versus 6 h) and solvent consumption (20 versus 100 mL) was achieved with a reproducibility (RSDs < 10%) comparable with that provided by the reflux extraction as a reference method.     

The Solvent‐Dependent Shift of the Amide I Band of a Fully Solvated Peptide as a Local Probe for the Solvent Composition in the Peptide/Solvent Interface

We determine the shift and line shape of the amide I band of a model AK peptide from molecular dynamics (MD) simulations of the peptide dissolved in methanol/water mixtures with varying composition. The IR spectra are determined from a transition dipole coupling exciton model. A simplified empirical model Hamiltonian is employed, which takes into account both the effect of hydrogen bonding and the intramolecular vibrational coupling. We consider a single isolated AK peptide in a mostly helical conformation, while the solvent is represented by 2600 methanol or water molecules, simulated for a pressure of 1 bar and a temperature of 300 K. Over the course of the simulations, minor reversible conformational changes at the termini are observed, which are found to only slightly affect the calculated spectral properties. Over the entire composition range, which varies from pure water to the pure methanol solvent, a monotonous shift towards higher frequency of the IR amide I band of about 8 wavenumbers is observed. This shift towards higher frequency is comparable to the shift found in preliminary experimental data also presented here on the amide I′ band. The shift is found to be caused by two counter‐compensating effects. An intramolecular red shift of about 1.2 wavenumbers occurs, due to stronger intramolecular hydrogen bonding in a methanol‐rich environment. Dominating, however, is the intermolecular solvent‐dependent shift towards higher frequency of about 10 wavenumbers, which is attributed to the less effective hydrogen‐bond‐donor capabilities of methanol compared to water. The importance of the solvent contribution to the IR shift, as well as the significantly different hydrogen formation capabilities of water and methanol, makes the amide I band sensitive to composition changes in the local environment close to the peptide/solvent interface. This allows, in principle, an experimental determination of the composition of the solvent in close proximity to the peptide surface. For the AK peptide case, we observe at low methanol concentrations a significantly enhanced methanol concentration at the peptide/solvent interface, supposedly promoted by the partially hydrophobic character of the AK peptide’s solvent‐accessible surface.     

Strategies for the synthesis of 2-substituted indoles and indolines starting from acyclic alpha-phosphoryloxy enecarbamates

Strategies have been developed for the synthesis of 2-substituted indoles and indolines starting from acyclic alpha-phosphoryloxy enecarbamates. A highly chemoselective cross-coupling of N-(o-bromophenyl)-alpha-phosphoryloxyenecarbamates with boron nucleophiles enabled the efficient preparation of various N-(o-bromophenyl)enecarbamates, which served as useful precursors for subsequent Heck-type cyclization or 5-endo-trig aryl radical cyclization to furnish 2-substituted indoles or indolines, respectively.     

Optimization of an analytical procedure for the determination of banned azo dyes in leather

The possibility of improving an existing method, based on supercritical-fluid extraction (SFE) and microwave-assisted extraction (MAE), for the determination of banned azo dyes in leather has been studied. Thus, optimization of experimental conditions in different steps (degreasing, reduction, and extraction) of the analytical procedure was performed. The influence of different variables (reaction time, temperature, and concentration of reducing agent) on the reduction process was evaluated by use of a factorial design. It was found that the concentration of the reducing agent and the interaction between time and temperature were the most influential variables. Consequently, by applying a higher temperature, the reaction time could be halved. The use of acidified water as extraction solvent in MAE was also investigated. Usually 1 mol L^–1 HCl was superior to methanol and buffer in terms of extraction efficiency. In conclusion, the present method gave significantly higher recoveries in comparison with the original method. All dyes were determined indirectly by measuring their corresponding harmful amines, formed after reduction by use of sodium dithionite.     

Effect of temperature on pH measurements and acid-base equilibria in methanol-water mixtures

The knowledge of the acid-base equilibria in water-solvent mixtures of both common buffers and analytes is necessary in order to predict their retention as function of pH, solvent composition and temperature. This paper describes the effect of temperature on acid-base equilibria in methanol-water solvent mixtures commonly used as HPLC mobile phases. We measured the delta-correction parameter (delta = sw pH - ss pH = Ej - log sw(gamma)oh) between two pH scales: pH measured in the solvent concerned and referred to the same standard state, ss pH, and the pH measured in that solvent mixture but referred to water as standard state, sw pH, for several methanol compositions in the temperature range of 20-50 degrees C. These determinations suggest that the delta-term depends only on composition of the mixture and on temperature. In water-rich mixtures, for which methanol is below 40% (w/w), delta-term seems to be independent of temperature, within the experimental uncertainties, whereas for methanol content larger than 50% (w/w) the delta-correction decreases as temperature increases. We have attributed this decrease to a large increase in the medium effect when mixtures have more than 50% methanol. The pKa of five weak electrolytes of different chemical nature in 50% methanol-water at 20-50 degrees C are presented: the effect of temperature on pKa was large for amines, pyridine and phenol, but almost no dependence was found for benzoic acid. This indicates that buffers can play a critical role in affecting retention and selectivity in HPLC at temperatures far from 25 degrees C, particularlyfor co-eluted solutes.     

New process of low-temperature methanol synthesis from CO/CO_2/H_2 based on dual-catalysis

A new process of low-temperature methanol synthesis from CO/CO2/H2 based on dual-catalysis has been developed. Some alcohols, especially 2-alcohol, were found to have high catalytic promoting effect on the synthesis of methanol from CO hydrogenation. At 443 K and 5 MPa, the synthesis of methanol could process high effectively, resulting from the synergic catalysis of Cu/ZnO solid catalyst and 2-alcohol solvent catalyst. The primary results showed that when 2-butanol was used as reaction solvent, the one-pass average yield and the selectivity of methanol, in 40 h continuous reaction at temperature as low as 443 K and 5 MPa, were high up to 46.51% and 98.94% respectively. The catalytic activity was stable and the reaction temperature was 80 K or so lower than that in current industry synthesis process. This new process hopefully will become a practical method for methanol synthesis at low temperature.     

New process of low-temperature methanol synthesis from CO/CO2/H2 based on dual-catalysis

A new process of low-temperature methanol synthesis from CO/CO₂/H₂ based on dual-catalysis has been developed. Some alcohols, especially 2-alcohol, were found to have high catalytic promoting effect on the synthesis of methanol from CO hydrogenation. At 443 K and 5 MPa, the synthesis of methanol could process high effectively, resulting from the synergic catalysis of Cu/ZnO solid catalyst and 2-alcohol solvent catalyst. The primary results showed that when 2-butanol was used as reaction solvent, the one-pass average yield and the selectivity of methanol, in 40 h continuous reaction at temperature as low as 443 K and 5 MPa, were high up to 46.51% and 98.94% respectively. The catalytic activity was stable and the reaction temperature was 80 K or so lower than that in current industry synthesis process. This new process hopefully will become a practical method for methanol synthesis at low temperature.     

An efficient method for the synthesis of enol ethers and enecarbamates. Total syntheses of isoindolobenzazepine alkaloids, lennoxamine and chilenine

An efficient method for the synthesis of enol ethers and enecarbamates has been developed based on catalytic hydrosilane reduction of alpha-phosphonoxy enol ethers and alpha-phosphonoxy enecarbamates. This method has been applied to the total syntheses of two isoindolobenzazepine alkaloids, lennoxamine and chilenine.