Mixture Of Isomers Research Articles

Isomerism in Phenyl 2‐Pyridyl Ketoxime Metal Complexes

AbstractThe octahedral complex [RhCl2(ppkoH)(ppko)] (1) was obtained from the reaction between RhCl3 and phenyl 2‐pyridyl ketoxime (ppkoH). Attempts to prepare the corresponding octahedral platinum compound from K2PtCl6 gave instead the square planar [Pt2+(ppko)2] (2), but when the halogen was changed to bromine, the octahedral [Pt4+Br2(ppko)2] (3) was formed. The crystal structures were determined by X‐Ray crystallography. All the compounds have two N,N‐chelating oxime ligands. In 1, one of them is deprotonated, while in 2 and 3 both ligands are deprotonated. Compounds 1 and 3 have two halogen ligands in trans position. In 1 the oxime groups are situated mutually in cis position with an intramolecular hydrogen bond between the two N−O(H) groups. The formation of 2 involves reduction of the platinum metal and the complex has oximes in trans position to each other. Compound 3 has an all‐trans geometry. Since octahedral and square planar compounds have a possibility to isomerism, we studied the relative stability of different geometries by DFT calculations. A mixture of isomers is likely to be formed in the reactions, but the most stable form was found to crystallize. The properties of the electron density in the preferred isomers were also investigated via QTAIM methods.

Simultaneous Cycloadditions in the Solid State via Supramolecular Assembly

AbstractChemical reactions conducted in the solid phase (specifically, crystalline) are much less numerous than solution reactions, primarily due to reduced motion, flexibility, and reactivity. The main advantage of crystalline‐state transformations is that reactant molecules can be designed to self‐assemble into specific spatial arrangements, often leading to high control over product regiochemistry and/or stereochemistry. In crystalline‐phase transformations, typically only one type of reaction occurs, and a sacrificial template molecule is frequently used to facilitate self‐assembly, similar to a catalyst or enzyme. Here, we demonstrate the first system designed to undergo two chemically unique and orthogonal cycloaddition reactions simultaneously within a single crystalline solid. Well‐controlled supramolecular self‐assembly of two molecules containing different reactive moieties affords orthogonal reactivity without use of a sacrificial template. Using only UV light, the simultaneous [2+2] and [4+4] cycloadditions are achieved regiospecifically, stereospecifically, and products are obtained in high yield, whereas a simultaneous solution‐state reaction affords a mixture of isomers in low yield. Application of dually‐reactive systems toward (supra)molecular solar thermal storage materials is also discussed. This work demonstrates fundamental chemical approaches for orthogonal reactivity in the crystalline state and highlights the complexity and reversibility that can be achieved with supramolecular design.

Scalable synthesis of tranexamic acid under modest reaction conditions using early stage isomerization of dimethyl 1,4-cyclohexanedicarboxylate as a key step

A commercially scalable five-step synthetic process starting from cis/trans (7:3) mixture of dimethyl 1,4-cyclohexanedicarboxylate is devised for preparation of tranexamic acid with more than 99.5% purity. All impurities are controlled as per monograph. 47% overall yield over five steps has been achieved based on recovery. Epimerization of a cis-predominant isomeric mixture to trans predominant isomeric mixture under mild conditions followed by exploiting the difference in solubility to obtain trans isomer in very high purity is the key feature of the synthesis. In addition to this, use of readily available and cost efficient raw materials/reagents, recycling of cis isomer, explicit design of downstream processing enabling the retention of the trans-stereochemistry until final API are some of the highlights of this synthesis. This process also circumvents the use of hazardous chemicals and harsh reaction conditions making it greener and safer compared to the previous reports.”

Bio-based nylon intermediates from γ-valerolactone: Catalyst modifications for an enhanced selectivity to methyl 4-pentenoate

Ring-opening transesterification of bio-based γ-valerolactone (GVL) to produce a mixture of methyl pentenoate isomers (MPs) such as methyl 4-pentenoate (M4P), methyl 3-pentenoate (M3P) and methyl 2-pentenoate (M2P) has been carried out using modified Zr-containing catalysts in a gas phase continuous process. As the three MP isomers are potential nylon intermediates, this approach is sustainable from a green chemistry point of view to synthesize bio-based polymers. The reaction was carried out in a fixed bed catalytic reactor at ambient pressure and in the temperature range from 255 to 335°C. In the present study, SiO2 supported zirconia catalysts were prepared by wet impregnation with varying Zr loadings in the range from 5 to 30wt%. The catalysts were characterized by various techniques. The surface areas were determined by N2 adsorption, acid-base properties by NH3-TPD and CO2-TPD techniques. In addition, the distinction of Lewis and Brønsted sites were also estimated by Py-FTIR. Among all catalysts, 25% Zr/SiO2 exhibited the best performance. The influence of various key reaction parameters on the activity/selectivity was explored and suitable reaction conditions were optimized. The conversion of GVL and product distribution was found to be strongly dependent on the reaction temperature and Zr content of the catalysts. The sum selectivity of all the three MP isomers varied in the range from 97 to 99%, of which M4P was always the dominant product. At low reaction temperature (255°C), M4P was the major product while M2P was a minor product. However, with increase in temperature, the selectivity of M2P and M3P increased at the expense of M4P due to isomerisation of the C=C double bond. In addition, the effect of support on the best Zr loading was also explored and it was found that the SiO2 support exhibited superior performance compared to others. In the direction of enhancing the selectivity of M4P, Cr-doping was also done onto 25Zr/SiO2, the best catalyst of this study. Such incorporation of chromium significantly enhanced the selectivity of M4P above 80% at acceptably high conversion of GVL.

A Dual CQD-Catalysis and H-Bond Acceptor for Controlling Product Selectivity and Regioselectivity in Symmetric/Unsymmetric Azoxy Arenes.

Azoxy arenes are valuable compounds in different areas of chemistry, such as organic chemistry, medicinal chemistry, and natural product chemistry. Despite their value, the regioselective synthesis of unsymmetric azoxybenzenes has remained a real challenge in the field. Herein, the product selectivity in oxidative homocoupling of anilines into symmetric azoxybenzenes was first achieved by an asparagine-functionalized CQD catalyst. Subsequently, in the cross-coupling of anilines into the unsymmetric azoxybenzenes via an ortho H-bond acceptor (HBA) on one of the coupling anilines, the regioselectivity was effectively controlled. It was demonstrated that ortho-HBA could mechanistically establish a six-membered intramolecular hydrogen-bonded ring on an N,N'-dihydroxy intermediate. The formed hydrogen bond makes the nearby nitrogen eminently suitable for the slow dehydration step. As a result, the functional oxygen of the azoxy compound is placed far from the HBA. The o-HBA mechanism also controls the regioselectivity ratio in which 1:0 (with an intramolecular H-bonded hexagonal ring), 2:1 (with an intramolecular H-bonded pentagonal ring), and 1:1 (without an ortho-HBA) isomeric mixtures could be achieved. The HBA mechanism was exploited by different substituted anilines, and various unsymmetric azoxybenzenes were synthesized. Finally, with the aid of mechanistic studies, a plausible mechanism for the reaction was proposed.

Can a Mixture of Farnesene Isomers Avert the Infestation of Aphids in Sugar Beet Crops?

The negative impact of pesticides on the environment and the potential of pest species to develop pesticide resistance make it necessary to explore new methods of pest control. Pheromones and other behavior-modifying semiochemicals are already important in integrated pest management (IPM). (E)-ß-farnesene (EBF) is a semiochemical that acts as an alarm pheromone in aphids. Upon perception of EBF, aphids stop feeding, move away, and sometimes even abandon the host plant. The aphids Myzus persicae and Aphis fabae are significant crop pests and vectors of many harmful phytopathogens affecting sugar beet (Beta vulgaris). Field trials were conducted at different locations in Germany to test whether dispensers containing a mixture of farnesene isomers (FIMs) including EBF were able to reduce the infestation of these species on sugar beet. Our results showed a reduction in aphid abundance in the FIM-treated patches in two out of three sites. Therefore, we hypothesize that FIM dispensers could prevent aphid infestation and could be used in combination with other IPM measures. However, more research is required to increase the effect and ensure the reliability of this method.

From dairy waste to value-added bio-based surfactants

Cheese whey permeate, the main waste stream of dairy industry, was used as a starting material for the production of bio-based surfactants (SFAEs). Specifically, the first step in the sustainable chemoenzymatic synthesis of n-butyl 6-O-palmitoyl-D-glycosides (Fischer glycosylation followed by enzymatic esterification) was optimized by a chemometric study. The surfactancy of the prepared isomeric mixtures was deeply investigated in terms of static and dynamic interfacial tension and emulsifying capability over time.

Simultaneous Cycloadditions in the Solid State via Supramolecular Assembly.

Chemical reactions conducted in the solid phase (specifically, crystalline) are much less numerous than solution reactions, primarily due to reduced motion, flexibility, and reactivity. The main advantage of crystalline-state transformations is that reactant molecules can be designed to self-assemble into specific spatial arrangements, often leading to high control over product regiochemistry and/or stereochemistry. In crystalline-phase transformations, typically only one type of reaction occurs, and a sacrificial template molecule is frequently used to facilitate self-assembly, similar to a catalyst or enzyme. Here, we demonstrate the first system designed to undergo two chemically unique and orthogonal cycloaddition reactions simultaneously within a single crystalline solid. Well-controlled supramolecular self-assembly of two molecules containing different reactive moieties affords orthogonal reactivity without use of a sacrificial template. Using only UV light, the simultaneous [2+2] and [4+4] cycloadditions are achieved regiospecifically, stereospecifically, and products are obtained in high yield, whereas a simultaneous solution-state reaction affords a mixture of isomers in low yield. Application of dually-reactive systems toward (supra)molecular solar thermal storage materials is also discussed. This work demonstrates fundamental chemical approaches for orthogonal reactivity in the crystalline state and highlights the complexity and reversibility that can be achieved with supramolecular design.

Palladium‐Catalyzed Enantioselective Migratory Hydroamidocarbonylation of Amide‐Linked Alkenes to Access Chiral α‐Alkyl Succinimides

AbstractA Pd‐catalyzed asymmetric isomerization‐hydroamidocarbonylation of amide‐containing alkenes was developed, affording a variety of chiral α‐alkyl succinimides in moderate to good yields with high enantioselectivities. The key to success was introducing bulky 1‐adamentyl P‐substitution and 2,3,5,6‐tetramethoxyphenyl group into the rigid P‐chirogenic bisphosphine ligand to create stronger steric hinderance and deeper catalytic pocket. By this approach, regio‐ or stereo‐convergent synthesis of enantiomeric succinimides from the mixture of olefin isomers was achieved.

Separation of triacylglycerol (TAG) isomers by cyclic ion mobility mass spectrometry

Triacylglycerols (TAGs), a major lipid class in foods and the human body, consist of three fatty acids esterified to a glycerol backbone. They can occur in various isomeric forms, including sn-positional, cis/trans configurational, acyl chain length, double bond positional, and mixed type isomers. Separating isomeric mixtures is of great interest as different isomers can have distinct influence on mechanisms, such as digestibility, oxidative stability, or lipid metabolism. However, TAG isomer separation remains challenging with established analytical methodologies such as liquid-chromatography coupled to mass spectrometry (LC-MS). In this study, we developed a method with cyclic ion mobility mass spectrometry (cIMS-MS) for the separation and identification of all types of TAG isomers. First, the influence of different adducts (Li+, NH4+, Na+, and K+) on the separation was studied. Overall, it was concluded that the sodium adduct is the best choice to efficiently separate all types of TAG isomers. In addition, trends were found in the influence of specific structural features on the drift time order. An order of relative influence (from high to low) was established; (1) degree of unsaturation of the fatty acid(s) on an exterior position (if the total degree of unsaturation(s) is equal in both TAGs), (2) acyl chain length on the exterior positions, (3) cis/trans configuration, and (4) double bond (DB)-position. Finally, various cIMS-MS strategies were developed for the separation of mixtures containing four, five, and six isomers. To conclude, the developed methods can be used for separation of complex mixtures of TAG isomers and have great potential to be expanded to isomers of similar types of lipids such as di- and monoacylglycerols. This study also shows the potential of cIMS-MS to be used for the application on real TAG samples.

Investigation of Neighboring Group Participation in 3,4-Diacetylated Glycosyl Donors in the Gas Phase.

A key challenge in oligosaccharide synthesis is the stereoselective installation of glycosidic bonds. Each glycosidic linkage has one of two possible stereo-chemical geometries, α/β or 1,2-cis/trans. An established approach to install 1,2-trans glycosidic bonds is neighboring group participation (NGP), mediated by a 2-O-acyl group. Extension of this intramolecular stabilization to nucleophilic groups located at more remote positions has also been suggested, but remains poorly understood. Previously, we employed infrared ion spectroscopy to characterize the molecular ions of monoacetylated sugar donors and showed how the strength of the stabilizing effect depends on the position of the participating ester group on the glycosyl donor ring as well as on its relative stereochemistry. In this work, we investigated glycosyl donors carrying two acyl groups. Using isotope labelling and isomer population analysis we were able to resolving spectra of isomeric mixtures and establish the relative contribution of individual species. We conclude that 3,4-diacetyl mannosyl donors exclusively form a dioxanium ion as a result of C-3 acyl stabilization. In contrast, the glucosyl and galactosyl cations form mixtures of C-3 and C-4 acyl participation products. Hence, the combination of isotope labeling and population analysis allows for the study of increasingly complex glycosyl cations.

Electrochemical oxidation of furans into 2,5-dimethoxy-2,5-dihydrofurans

Substituted 2,5-dimethoxy-2,5-dihydrofurans (cis/trans isomer mixtures) were obtained via the electrochemical oxidation of the corresponding furans in an undivided cell in methanol in the presence of bromides as mediators. The method is suitable for furans containing electron-donating groups.

Structural study of minor C84 isomers as chlorofullerenes, C84(11)Cl22, C84(14)Cl22, C84(16)Cl22, and C84(16)Cl24

Chlorofullerenes C84Cl22,24 were obtained by chlorination of minor C84 isomers mixture with VCl4 at 330 °C. An X-ray crystallographic study with the use of synchrotron radiation revealed the presence of C84(11)Cl22, C84(14)Cl22, C84(16)Cl22, and C84(16)Cl24 in the same crystal.

Asymmetric conjugate 1,6-addition of organocuprates to N-dienoyl oxazolidinones

A highly regioselective and diastereoselective conjugate 1,6-addition of organocuprates to N-dienoyl oxazolidinones to provide the 1,6-addition products, is described. These products have a β,γ-unsaturated olefin and a new asymmetric center at C(δ). The 1,6-addition products were obtained as a mixture of geometric isomers (E,Z), where its prevalence depends on reaction conditions and the type of Grignard reagent. This methodology can be carried out with small or voluminous alkyl Grignard reagents, aromatic or vinylic Grignard reagents, unlike other methodologies where there are difficulties with bulky Grignard reagents. It is the first paper describing a competition between geometric isomers (E, Z) into the 1,6- addition products depending on the employed reaction conditions. Chiral oxazolidinone moiety removal furnished chiral δ-substituted β,γ-unsaturated carboxylic acids.

Fluorescence and Photophysical Properties of Anthracene and Phenanthrene in Water.

Polyaromatic hydrocarbons (PAHs) are widely spread pollutants in the environment, including soil and water. Anthracene (anth) and phenanthrene (phen) pose severe health impacts on human lives due to their carcinogenic nature by increasing cancer risk to the skin, lungs, and bladder. Fluorescence spectroscopy is a promising , efficient and straightforward tool for characterizing these trace PAHs in water. Therefore, the current work provides a detailed insight into the fluorescence properties of anth and phen in water. The fluorescence EEMs (excitation-emission matrices) of anth showed emissions at 380nm, 400nm, and 425nm with single excitation at 250nm, whereas phen showed two emissions < 380nm, at 350nm and 365 with single excitation at 250nm. Then the theoretical EX/EM wavelengths were calculated by DFT and CIS-B3LYP for these compounds in water. The environmental effect of pH variation on fluorescence EEM shows a significant difference in fluorescence intensity without changing in peak locations, with highest fluorescence intensity at neutral pH than acidic and alkaline. Furthermore, the theoretical pH effect was described for the first time by simulating the protonated (+ 1), deprotonated (-1) and neutral molecules in water at the DFT level of theory. The variation in simulated oscillator strengths was similar in trend with the experimental fluorescence intensity of these compounds. The HOMO-LUMO were calculated to obtain the energy gap, molecular softness, molecular hardness, electronic potential and electrophilicity of anth and phen. To find the fluorophore contribution, the fluorescence of homogeneous mixture of both isomers was analyzed, which showed an enhanced fluorescence intensity of anth by 12-20%, whereas a decrease of 9-14% was observed in phen. This study describes that the fluorescence technique could be a fast and easy method to distinguish and identify PAHs isomers (anth and phen) in water.

Identifying and Quantifying Relative Concentrations of Epimers in Mixtures via Cyclic Ion Mobility Mass Spectrometry: Dexamethasone and Betamethasone as a Case Study.

Epimers can show different biological activities and different pharmacological behaviors; therefore, their separation and analysis are crucial in the drug development process. Due to their similar chemical and physical properties, separation of epimers is challenging. This study demonstrates the application of cyclic ion mobility-mass spectrometry to separate, identify, and quantify dexamethasone and betamethasone in a binary mixture. Cyclic IMS separation of the isolated protonated dimer resulted in three peaks: dexamethasone homodimer, betamethasone homodimer, and their heterodimer. Besides providing improved separation over the protonated monomer, the presence of a heterodimer peak provides additional confirmation of an isomeric mixture. We identified the dexamethasone and betamethasone homodimer peaks by infusing pure solutions of each epimer and measuring each pure homodimer's arrival time. The measured peak areas indicated that the heterodimer is formed at twice the rate of each homodimer and that dexamethasone and betamethasone contribute equally to the heterodimer signal. Using this observation, we could accurately calculate the relative concentrations of each epimer by adding half of the heterodimer peak area to each homodimer peak area. These findings enable the identification and quantification of dexamethasone and betamethasone based on the arrival time distributions of their protonated dimers. This is the first demonstration of accurate relative quantification of epimers by separating charged dimers in the gas phase.

Self-assembly via hydrogen bonding of bis(18-crown-6)-1,3-distyrylbenzene and [2 + 2] photocycloaddition: Stereoselective synthesis of [2.2]metacyclophanes and butterfly-type thermal isomerization

The photochemistry of bis(18-crown-6)-containing 1,3-distyrylbenzene and its 2 : 2 bis-pseudo-sandwich complex with ethane-1,2-diammonium was studied. The UV irradiation of the supramolecular complex resulted in the formation of three geometric isomers of tetracrown-containing dicyclobutano[2.2]metacyclopane, differing in the orientation of the cyclobutane moieties, with the unsymmetrical isomer (>50 %) predominating. The diammonium cations used as the template could be removed after photolysis by simple extraction, and the product was obtained in high yield (82 %). The 1H NMR signals of a mixture of geometric isomers of [2.2]metacyclophane derivative were assigned resorting to quantum chemistry methods (DFT). The kinetic and thermodynamic parameters of thermal isomerization between the endo,endo- and exo,exo-isomers were measured. Tetracrown-containing dicyclobutano[2.2]metacyclophanes are homotetratopic ligands that contain four binding sites for metal and ammonium cations, which is of interest for the design of photo- and thermo-switchable supramolecular devices with a variable complex formation behavior and supramolecular machines owing to the butterfly-type thermal isomerization.

Synthesis of Bifluorenylidene- and Cycloocta[1,2,3-jk:6,5,4-j′k′]difluorene-Extended Tetrathiafulvalenes: Novel Multi-Redox Systems

AbstractHerein, we present the synthesis of a novel 9,9′-bifluorenylidene-extended tetrathiafulvalene (TTF) as an E/Z isomeric mixture that was found to readily undergo an oxidative dimerization to furnish a TTF vinylogue with the two dithiafulvene units connected to an eight-membered ring fused to a bifluorenylidene core. This compound exhibited multiredox behavior and was found to take six charge states under cyclic voltammetry conditions: –2, –1, 0, +1, +2, +3. The dication corresponds to a cycloocta[1,2,3-jk:6,5,4-j′k′]difluorene with two appended 1,3-dithiolium rings.

Stilbenes in Carex acuta and Carex lepidocarpa.

Stilbenes in the roots of Carex acuta and Carex lepidocarpa were studied. Root samples were extracted with 100% methanol and analyzed by HPLC and LC-MS. In this way, trans-resveratrol dimers (m/z 455 Da [M + H]+), trimers (m/z 681 Da [M + H]+) and tetramers (m/z 907 Da [M + H]+) were identified in the extracts. Using LC-NMR in stop-flow mode, pallidol and trans-ε-viniferin as dimers were identified. After the separation of individual peaks and their measurement by 1H NMR, cis and trans-miyabenol A as a tetramer and cis-miyabenol C as a trimer were identified. In the case of miyabenol A, it is a chromatographically inseparable mixture of cis and trans isomers in the ratio of 2:3 according to 1H NMR measurement. In the case of cis-miyabenol C, the Z-trans-trans-miyabenol C configuration was confirmed. The remaining unidentified peak with a practically identical UV-VIS spectrum to that of cis-miyabenol C is most likely another isomer of miyabenol C.

Efficient separation of linear and mono-branched hexane isomers using large-area silicalite-1 membranes

Membrane-based hydrocarbon isomer separation is a promising and energy-saving alternative to distillation. For the first time, tubular silicalite-1 membranes with large areas of 180 cm2 were employed in this study to separate linear and mono-branched hexane isomers. The membrane had a thickness of around 8 μm and showed highly (h0h) orientation. In binary and ternary mixtures of n-hexane (n-C6), 2-methylpentane (2MP), and 3-methylpentane (3MP), the effects of temperature and partial pressure on the separation performance of silicalite-1 membrane were examined. Moreover, the long-term stability of the membrane in binary and ternary mixture separation was also investigated. The large-area membrane showed a n-C6 permeance of 2.4 × 10-8 mol/(m2 s Pa) and n-C6/2MP and n-C6/3MP separation factors of 36 and 74 in the ternary n-C6/2MP/3MP (2.8 kPa/2.9 kPa/2.8 kPa) mixture with N2 as the balanced gas at 100 kPa absolute and 303 K, respectively. The scaling-up membranes demonstrated good and stable separation performance during the long-term test, highlighting the effectiveness and potential application of using large-area silicalite-1 membranes for the separation of hexane isomer mixtures.