Dibenzoyltartaric Acid Research Articles

The Optimization of the Synthesis Process and the Identification of Levobupivacaine Hydrochloride.

In this study, we not only optimized and improved the synthesis process of levobupivacaine hydrochloride (21) but also conducted a comprehensive exploration of critical industrial-scale production details, and a novel high-performance liquid chromatography (HPLC) analysis method was developed. Starting with the readily available and cost-effective (R,S)-N-(2,6-dimethylphenyl)piperidine-2-carboxamide (28) as the initial material and utilizing l-(-)-dibenzoyl tartaric acid (29) for chiral separation, and then through substitution and a salting reaction, levobupivacaine hydrochloride (21) was obtained with high purity (chemical purity of 99.90% and enantiomeric excess (ee) values of 99.30%). The total yield of the three steps was 45%. Structures of intermediates and the final product were confirmed using nuclear magnetic resonance (NMR) (1H NMR, 13C NMR), mass spectrometry (MS), and elemental analysis. The crystal structure of the final product was determined through differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction (XRD). Furthermore, we evaluated the risk of the substitution reaction using a reaction calorimeter and accelerating rate calorimetry (ARC). This process offers the advantages of simple operation, greenness, safety, controllable quality, and cost-effectiveness. It provides reliable technical support for the industrial-scale production of levobupivacaine hydrochloride (21), which is of significant importance in meeting clinical demands. Pilot-scale production has already been successfully completed by China National Medicines Guorui Pharmaceutical Co., Ltd., with a production scale of 20 kg.

Ligand as Buffer for Improving Chemical Stability of Coordination Polymers.

Chemical stability is one of the key concerns in coordination polymers (CPs). However, technologies to protect CPs against acidic or alkaline aqueous environments have yet to be implemented. Herein we demonstrate an approach for improving the pH stability by utilizing the ligand salt as buffering site to modify the unsaturated coordination sites of CPs. For the selective one-dimensional CP Eu-d-DBTA (d-H2DBTA = d-O,O'-dibenzoyltartaric acid) with a pH stability range of 6-8, the introduction of the ligand salt Na-d-DBTA extends the pH stability interval from 3 to 11. Crystallographic structure data reveal the formation of a Eu/Na-d-DBTA dynamic structure with Na-d-DBTA buffer sites on the Eu-O cluster of the Eu-d-DBTA skeleton. Benefiting from the dynamic single-crystal-to-single-crystal transformation, the buffer sites protect the skeleton from the impact of the acidic or alkaline aqueous environment. In addition, Eu/Na-d-DBTA produces stable photoluminescence properties and selective responses toward l-tryptophan (l-Trp) and further toward l-lysine (l-Lys) over the whole buffer capacity range of 3-11. Noticeably, other Ln/Na-d-DBTA CPs and star metal-organic frameworks also exhibit pH stability improvement when the ligand-as-buffer technology is used, which is significant for developing advanced inorganic-organic hybrid materials with superior functionality.

Optical Resolution of Two Pharmaceutical Bases with Various Uses of Tartaric Acid Derivatives and Their Sodium Salts: Racemic Ephedrine and Chloramphenicol Base.

The optically active dibenzoyltartaric acid, tartaric acid, and its sodium salts were successfully applied to the optical resolution of (1R,2S)(1S,2R)-2-(methylamino)-1-phenylpropan-1-ol (EPH) and (1R,2R)(1S,2S)-2-amino-1-(4-nitrophenyl)propane-1,3-diol (AD) as resolving agents. It was observed that both compounds’ resolution using a mixture of salts of quasi-racemic resolving agents showed a change in chiral recognition under the same conditions compared to the result of the use of the single enantiomeric resolving agent. The changes are followed by detailed analytical (XRD, FTIR, and DSC) studies. Meanwhile, the DASH indexing software package was also tested on powder XRD patterns of pure initial materials and intermediate salt samples of high diastereomeric excess.

Synthesis, crystal structure and magnetic properties of a one-dimensional Mn2+ complex constructed from (+)-dibenzoyltartaric acid and 2,2'-bipyridine.

The self-assembly reaction of (+)-dibenzoyltartaric acid (D-H2DBTA) with 2,2'-bipyridine (bpy) and Mn(CH3CO2)2·4H2O yielded a new coordination polymer, namely, catena-poly[[[diaqua(2,2'-bipyridine-κ2N,N')manganese(II)]-μ-2,3-bis(benzoyloxy)butanedioato-κ2O2:O3] dihydrate], {[Mn(C18H12O8)(C10H8N2)(H2O)2]·2H2O}n or {[Mn(DBTA)(bpy)(H2O)2]·2H2O}n, (I). Complex (I) has been characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis (TGA) and single-crystal and powder X-ray diffraction. It crystallizes in the orthorhombic space group P212121. In the complex, the Mn2+ cation displays a distorted octahedral {MnO4N2} geometry, formed from two carboxylate O atoms of two DBTA2- ligands, two cis-oriented N atoms from one chelating 2,2'-bipyridine ligand and two trans-oriented O atoms from coordinated water molecules. The polymer displays a 1D chain with an Mn...Mn distance of 9.428 (1) Å. Due to the presence of flexible polycarboxylate and rigid bipyridyl ligands in the molecular structure, a high thermal stability of the complex is attained. The magnetic properties of (I) were analyzed based on the mononuclear Mn2+ model due to the long intramolecular Mn...Mn distance. The zero field splitting (ZFS) contribution in the high-spin Mn2+ cation is almost negligible and there are weak antiferromagnetic couplings between 1D chains [zJ' = -0.062 (5) cm-1], corresponding to an intermolecular Mn...Mn distance of 7.860 (2) Å.

Luminescence-Color-Changing Sensing toward Melamine Based on a White-Light-Emitting Film

Isostructural lanthanide coordination polymers, [Ln(d-DBTA)(d-HDBTA)(H2O)5]n (Ln-d-DBTA; d-H2DBTA = d-O,O′-dibenzoyl tartaric acid; Ln = La, Ce, Nd, Eu, Gd, and Tb), are synthesized and characterized. By uniformly doping this amphophilic Ln-d-DBTA into a poly(methyl methacrylate) (PMMA) matrix, we prepare stable films with tunable luminescence color, even white-light emission. Except for providing the blue-light component, the PMMA matrix plays indispensable roles in dispersing the 1D LnCPs via hydrogen bonds, transferring electrons to organic ligands by means of photoinduced electron transfer, and further sensitizing the luminescence of lanthanide ions. Then, a bifunctional sensing process toward melamine in various dairy products is conducted in terms of luminescent intensity and color. Consequently, the as-prepared white-light-emitting film exhibits 0.012 mg/kg limit of detection and obvious luminescence-color changes from white to blue. The excellent sensitivity, reliability, selectivity, stability, competitiveness, and recyclability state the promising practicality in monitoring quality of dairy products. In this work, using a battery of experimental techniques and theoretical calculation, we show how the PMMA matrix connects the LnCPs and promotes their photophysical properties, what changes have taken place for the energy- and electron-transfer pathways of the as-prepared chemosensor after adsorbing melamine, and why this convenient testing material is applicable.

PHANE‐TetraPHOS, the First D2 Symmetric Chiral Tetraphosphane. Synthesis, Metal Complexation, and Application in Homogeneous Stereoselective Hydrogenation

AbstractPHANE‐TetraPHOS, a new D2 symmetric tetraphosphane based on the [2.2]paracyclophane scaffold, has been synthesized and characterized. The peculiarity of this system is the presence of four homotopic diphenylphosphane groups, exchangeable through C2 symmetry operations and consequently indistinguishable. Their spatial arrangement allows the simultaneous complexation of two metal atoms. Enantiomeric purity was attained at tetra‐phosphane oxide level by fractional crystallization of the diastereomeric adducts obtained from the racemate with enantiopure dibenzoyltartaric acids. Alkaline treatment of diastereomerically pure adducts followed by exhaustive P−O groups reduction with HSiCl3 gave both PHANE‐TetraPHOS antipodes in an enantiopure state. They were tested as rhodium ligands in the homogeneous enantioselective hydrogenation of some benchmark unsaturated compounds. Catalytic activity and enantiodiscrimination ability were found comparable to those exhibited by the complexes of the parent bidentate ligand PHANEPHOS, but only half a mole of precious chiral ligand was employed.

Negative nonlinear CD-<italic>ee</italic> dependence in dibenzoyltartaric acid induced aggregates of perylenebisimide

Supramolecular chirality of aggregates can be described in terms of the CD signals of the aggregates as a function of the enantiomeric excess of the chiral building block or chiral inducer. While many examples have been reported that show a positive nonlinear CD- ee relationship, indicating chiral amplification, the negative nonlinear dependence has rarely been observed. We recently proposed to build such supramolecular aggregates by using the mesomer of the enantiomeric inducers. Indeed we found that in the presence of enantiomeric dibenzoyltartaric acids (DboTar), achiral perylenebisimide (PBI) dye equipped with two terminal guanidinium groups in alkaline aqueous buffer solution is induced to form chiral supramolecular aggregates, via the known guanidinium-carboxylate salt bridge, that show a positive nonlinear CD- ee relationship, and is turned into negatively nonlinear when 40% or more molar fraction of meso -DboTar was introduced. Absorption and CD spectral titrations suggest that the aggregates led by enantiomers and by mesomer are similar in terms of the supramolecular structure and stability, and when the two kinds of aggregates are mixed no molecular exchange occurs between them. Fluorescence spectral traces of the aggregates show that the mesomer is more powerful in inducing the aggregation of the PBI dyes, and thus dominates the aggregation. Our findings that the mesomer of the enantiomeric inducer could lead to aggregates to exhibit a negative nonlinear CD- ee relationship provide a promising approach to such supramolecular aggregates, which could be of significance for better insight into the mechanism leading to the negative nonlinear dependence and eventually a comprehensive understanding of the supramolecular chirality.

Coordination Compounds Featuring Non-Toxic Chiral 1,4-Dicarboxylic Acids and Copper(II)

Six new coordination compounds of copper cations and 1,4-dicarboxylic acids have been synthesized and structurally investigated. Aspartic acid (H2asp), enantiopure, racemic and meso tartaric acid (H2tart), di-para-toluyltartaric acid (H2dptta) and dibenzoyltartaric acid (H2dbta) represent environmentally benign water-soluble proligands which may be deprotonated for oxygen coordination. Chelating ligands such as tetramethylethylenediamine (TMEDA) and 2-aminomethylpyridine (AMPY) efficiently reduce the dimensionality of the target compounds, and additional aqua ligands complete the coordination environments. In this line of argument, the discrete mononuclear complexes [Cu(AMPY)(asp)(H2O)] and [Cu(Hdbta)2(H2O)4] were obtained; for the latter, only a preliminary structure model can be presented which, however, agrees with the powder diffraction pattern of the bulk. From enantiopure and racemic tartaric acid and TMEDA the closely related chain polymers [CuII(H2tart)(TMEDA)(H2O)2)]n were obtained; the racemic compound consists of individual homochiral strands of opposite chirality. The high steric demand of di-para-toluyltartaric acid leads to one-dimensional [Cu(dptta)(EtOH)(H2O)2]n with coordinated ethanol (EtOH) in the distant Jahn–Teller site of the coordination sphere. Cu(II), meso-tartaric acid and TMEDA aggregate to a trinuclear coordination compound [CuII2CuI(H2tart)(Htart)(TMEDA)2]. Its peripheral cations show the expected Jahn–Teller geometry of Cu(II), but the unambiguous assignment of the oxidation state +I for central cation required susceptibility measurements: their results prove the presence of only two and only very weakly interacting divalent cations, separated by a diamagnetic center.

Calcium(II)-mediated resolution of methyl o-chloromandelate with chiral O,O′-dibenzoyltartaric acid in preparative scale

Abstract We report here the coordination-mediated resolution of methyl o-chloromandelate, which is a key intermediate for clopidogrel, in preparative scale. The reaction of CaO, optically pure (2R, 3R)-O,O′-dibenzoyltartaric acid, and methyl o-chloromandelate in ethanol solution afforded a mixed-ligands calcium(II) complex that was further purified by stirring of the crystals in hot methanol. Methyl (R)-o-chloromandelate was obtained in good enantiomeric excess value (>99.5%) and yield (71%) by treatment of the complex with acid. At the same time, (2R, 3R)-O,O′-dibenzoyltartaric acid was recovered in 72% yield. In addition, methyl (S)-o-chloromandelate was obtained in good enantiomeric excess value (>99.5%) and yield (73%) by recovery from the mother liquor and resolution with the same procedure for methyl (R)-o-chloromandelate, except that (2S, 3S)-O,O′-dibenzoyltartaric acid was used as the resolving reagent.

Facile synthesis of chiral (right-handed) calcium carbonate with exceptional enantioseparation performance of dibenzoyltartaric acid

The chiral morphology of calcium carbonate (mainly vaterite) was successfully synthesized by using CaCl2 under l-aspartic acid guiding by diffusion of in-site generation of CO2 and NH3 from (NH4)2CO3 and NH3·H2O. Its structure was characterized by XRD, SEM/TEM and FT-IR, it indicated that the helical-shaped chiral calcium carbonate was uniform in a diameter of 10–20 μm and height of 1 μm, and tortuous nanosheets with a thickness of 50 nm were evolved more abundant from center to edge in counterclockwise. The enantioseparation performance for racemic dibenzoyltartaric acid was evaluated, the chiral calcium carbonate showed certain recognition ability for l-dibenzoyltartaric acid due to its better matching with l-dibenzoyltartaric acid molecules in stereochemical structure. Chiral separation ability for dibenzoyltartaric acid could be significantly improved by dibutyl maleate modification of chiral calcium carbonate; the maximal ee values for dibenzoyltartaric acid increased from 20.62% to 62.15%. The synergism of chiral helical-shaped suprastructure, large proportion of vaterite and modification of surface by functional group resulted in the excellent enantiomer separation.

2D double-layered dibenzoyl-tartrate chiral coordination polymer containing [Mn4L2(bpp)4] tetrahedral cage

The solution reactions of metal salts with (+)-dibenzoyl-tartaric acid (H2L) and 1,3-bis(4-pyridyl)propane (bpp) or 4,4′-bipyridine (4,4′-bipy) afford three two-dimensional (2D) coordination polymers, [Mn2L2(bpp)2(H2O)4]n·nH2O (1), [CuL(bpp)]n·nH2O (2) and [CoL(4,4′-bipy)(CH3OH)(H2O)]n (3). Dibenzoyl-tartrate ligand displays cis- or trans-conformation, and acts as a 1,4-dicarboxylate linker. Complex 1 features a beautiful 2D double-layered (4,4) network containing [Mn4L2(bpp)4] tetrahedral cage. The flexible bpp ligand links Mn(II) to form an interesting 64-membered saddle-shaped macrocycle [Mn4(bpp)4]. Complex 2 displays a 2D wave-like network assembled by 1D [CuL]n linear chain and 1D [Cu(bpp)]n zigzag chain. Complex 3 is a 2D layered network constructing from [CoL(CH3OH)(H2O)]n chain and [Co(4,4′-bipy)]n chain.

A highly sensitive sensor for ethyl acetate by changing fluorescent colour of lanthanide complex

A lanthanide complex, namely, [La2 (L-DBTA)3 (CH3 OH)2 (H2 O)2 ]∙2H2O has been synthesized using a simple reaction of L-O,O´-dibenzoyl tartaric acid with LaCl3 ∙6H2 O under ambient temperature. The luminescence spectrum in the solid state at room temperature revealed that the complex exhibited blue-light emission that originated from ligand. In addition, the lanthanide complex is developed as a fluorescent probe for sensing small molecules. Luminescence studies reveal that the lanthanide complex could detect ethyl acetate sensitively through fluorescence colour change from blue to yellow. Furthermore, the complex exhibited appealing features including high sensitivity and an ultrafast response.

Enantioenrichment of a tungsten dearomatization agent utilizing chiral acids.

A method is described for the resolution of the versatile dearomatization reagent TpW(NO)(PMe3)(η(2)-benzene), in which the 1,3-dimethoxybenzene (DMB) analogue of this complex is synthesized. In turn, the coordinated arene of TpW(NO)(PMe3)(DMB) is protonated with either D or L dibenzoyl tartaric acid (DBTH2) in a butanone/water or 2-pentanone/water solution. Sustained stirring of this mixture results in the selective precipitation of a single form of the diastereomeric salt [TpW(NO)(PMe3)(DMBH)](DBTH). After isolation, the salt can be redissolved, and the DMB ligand can be deprotonated and exchanged for benzene to produce the desired product TpW(NO)(PMe3)(η(2)-benzene) in either its R or S form. The absolute configuration of the tungsten stereocenter in TpW(NO)(PMe3)(η(2)-benzene) can be determined in either case by substituting the naturally occurring terpene (S)-β-pinene for benzene and evaluating the 2D NMR spectrum of the corresponding β-pinene complex.

Molecular recognition directed supramolecular control over perylene-bisimide aggregation resulting in aggregation induced enhanced emission (AIEE) and induced chiral amplification

Achiral functional perylene recognizes only dibenzoyl tartaric acid (d/l) among others by expressing different self-assembled structures, and the selectivity is further transferred to chiral amplification in an enantiomeric excess experiment.

Chiral tetrakis(4-carboxyphenyl)porphyrin aggregates induced by enantiomeric dibenzoyl tartaric acids at the air–water interface

Abstract Enantiomeric dibenzoyl tartaric acid (DBTarA)-induced formation of chiral tetrakis(4-carboxyphenyl)porphyrin (TCPP) aggregates have been investigated in solutions and at the air–water interface. Surface pressure–area isotherms of the monolayers, UV–vis, and infrared spectra, as well as X-ray photoelectron spectra of the transferred Langmuir–Blodgett (LB) films, indicated that, though the small DBTarA molecules had difficulty forming insoluble monolayers at the interfaces, they could insert themselves in the matrix of porphyrins to form TCPP-DBTarA mixed monolayers and LB films. The inorganic salt of CdCl2 in the subphase could stabilize the mixed monolayers due to formation of the coordination bond between Cd(II) ions and carboxylic acid substituents of TCPP and DBTarA. Mirror-imaged circular dichroism spectra were recorded with two signals centered at about 230–250 and 400–450 nm; the former indicated that chirality of the DBTarA remained in the LB films while the latter (corresponding to the Soret absorption band of porphyrins) indicated that the co-existing DBTarA could induce the formation of supramolecular chirality in the porphyrins. It was revealed that pure TCPP formed dot-like aggregates while its mixtures with DBTarA formed irregular nanowires on the CdCl2 subphase surface, a phenomenon which may be attributed to the fact that the coordination bond of Cd OOC connects TCPP and DBTarA molecules to form larger one-dimensional ternary molecular assemblies.

Syntheses of Four Enantiomers of 2,3-Diendo- and 3-Endo-aminobicyclo[2.2.2]oct-5-ene-2-exo-carboxylic Acid and Their Saturated Analogues

Ethyl 2,3-diendo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylate ((±)-1) was resolved with O,O'-dibenzoyltartaric acid via diastereomeric salt formation. The efficient synthesis of the enantiomers of 2,3-diendo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid ((+)-7 and (–)-7), 3-endo-aminobicyclo[2.2.2]oct-5-ene-2-exo-carboxylic acid ((+)-5 and (–)-5), cis- and trans-3-aminobicyclo[2.2.2]octane-2-carboxylic acid ((+)-6, (–)-6, (+)-8 and (–)-8) was achieved via isomerization, hydrogenation and hydrolysis of the corresponding esters (–)-1 and (+)-1. The stereochemistry and relative configurations of the synthesized compounds were determined by NMR spectroscopy (based on the 3J(H,H) coupling constants) and X-ray crystallography.

Deracemization of Axially Chiral Nicotinamides by Dynamic Salt Formation with Enantiopure Dibenzoyltartaric Acid (DBTA)

Dynamic atroposelective resolution of chiral salts derived from oily racemic nicotinamides and enantiopure dibenzoyltartaric acid (DBTA) was achieved by crystallization. The absolute structures of the axial chiral nicotinamides were determined by X-ray structural analysis. The chirality could be controlled by the selection of enantiopure DBTA as a chiral auxiliary. The axial chirality generated by dynamic salt formation was retained for a long period after dissolving the chiral salt in solution even after removal of the chiral acid. The rate of racemization of nicotinamides could be controlled based on the temperature and solvent properties, and that of the salts was prolonged compared to free nicotinamides, as the molecular structure of the pyridinium ion in the salts was different from that of acid-free nicotinamides.

Chiral Discrimination of the Diastereomeric Salts with (R)-Nipecotic Acid and Tartaric Acid Derivative

An effective resolving agent, (D)-dibenzoyl tartaric acid (2b), was screened to yield direct resolution of (S)- ethyl nipecotate (1) with high optical purity and yield. Molecular recognition was studied by 1H NMR, IR, DSC and single crystal diffraction of the pair of diastereomeric salts. The less-soluble salt formed a supra molecular structure by enantio differentiating self-assembly.

Asymmetric Noncovalent Synthesis of Self-Assembled One-Dimensional Stacks by a Chiral Supramolecular Auxiliary Approach

Stereoselective noncovalent synthesis of one-dimensional helical self-assembled stacks of achiral oligo(p-phenylenevinylene) ureidotriazine (AOPV3) monomers is obtained by a chiral supramolecular auxiliary approach. The racemic mixture of helical stacks of achiral AOPV3 molecules is converted into homochiral helical stacks, as shown by both spectroscopic measurements and molecular modeling simulations. The conversion is promoted by an orthogonal two-point ion-pair interaction with the chiral auxiliary dibenzoyl tartaric acid (D- or L-TA) molecules, which biases the angle population distribution and thereby the stack helicity. The induced preferred helicity is maintained by the OPV stacks even after the removal of the chiral auxiliary by extraction with ethylenediamine (EDA), due to the kinetic stability of the OPV stacks at room temperature. Spectroscopic probing of the helical self-assembly and the racemization process of these π-conjugated OPV chromophores shed further light into the mechanistic pathways of this chiral asymmetric noncovalent synthesis and the kinetic stability of the stacks produced. The racemization of the stacks follows first-order kinetics and no switch in mechanism is observed as a result of a temperature change; therefore, a racemization via disassembly assembly is proposed. Remarkably, the preferred helicity of the stacks of achiral AOPV3 can be retained almost completely after a heating-cooling cycle where the stacks first partially depolymerize and then polymerize again with the still existing stacks being the seeds for self-assembly of achiral AOPV3. Only after a fully dissociated state is obtained at high temperatures, the optical activity of the supramolecular stack self-assembled at room temperature is lost.

Study on the Synthesis and Resolution of Dl-Ephedrine

For curing the common cold due to windcold , bosom frowsty cough, feng shui edema, bronchial asthma disease and etc, DL-ephedrine was synthesized by taking α-(Methylamino) propiophenone as the starting material followed reduction reaction. L-(-)-dibenzoyltartaric acid was used to resolve DL-ephedrine to get optically pure isomers D-(-)-ephedrine and L-(+)-ephedrine.Chemical structure was confirmed by IR and optical purify was up to grade.