Riina Aav

Preparation of highly enantiopure stereoisomers of 1-(2,6-dimethylphenoxy)-2-aminopropane (mexiletine)

Abstract Mexiletine [1-(2,6-dimethylphenoxy)-2-aminopropane], an orally effective antiarrhythmic agent, exhibits enantioselective pharmacokinetics and pharmacodynamics during mexiletine therapy. The purpose of this paper is to emphasize the advantage of tetrahydropyranyl-protected mandelic acid (THPMA) in the resolution of mexiletine enantiomers. Both enantiomers of mexiletine were obtained in 99% enantiomeric excess. Judging by the differential shielding effects in the 1 H and 13 C NMR analyses, we have observed the opposite predominant conformation for the mexiletine mandelates in comparison with the O -methylmandelates.

New homologues of chiral cyclohexylhemicucurbit[n]urils

The existence of new 7-, 8-, 9- and 10-membered homologues of chiral cyclohexylhemicucurbituril is reported. The barrel-shaped (all-R)-cyclohexylhemicucurbit[8]uril ((all-R)-cycHC[8]) was isolated and its complexes with anions were detected in negative ion mode MS. Here, 7-, 9- and 10-membered homologues were detected by HPLC–HRMS. Geometries of all reported macrocycles were calculated using quantum chemical methods, which showed that even-numbered homologues were barrel-shaped and odd-numbered homologues were asymmetrical barrel-shaped with unequal dimensions of the openings. The size of the ((all-R)-cycHC[8]) cavity was comparable to CB[8] and it probably can serve as a chiral host.

Synthesis and Characterisation of Chiral Triazole‐Based Halogen‐Bond Donors: Halogen Bonds in the Solid State and in Solution

A general platform for the synthesis of various chiral halogen-bond (XB) donors based on the triazole core and the characterisation of factors that influence the strength of the halogen bond in the solid state and in solution are reported. The characterisation of XB donors in the solid state by X-ray crystallography and in solution by 1 H NMR titration can be used to aid the design of new XB donors. We describe the first example of a XB between iodotriazoles and thioureas in solution. In addition, the enantiodiscrimination of acceptors in solution through halogen-bond participation is described.

Organic acid catalyzed synthesis of 5-methylresorcinol based organic aerogels in acetonitrile

A method of preparing 5-methylresorcinol and formaldehyde based organic aerogels in non-aqueous media with a benzoic acid derivative as a catalyst is being proposed in this paper. Here acetonitrile is used as a solvent that allows direct drying with carbon dioxide over the supercritical state without the need for a solvent exchange. The acidic properties of 2,6-dihydroxy-4-methyl benzoic acid promote the reaction of sol–gel polymerization, and at the same time it takes part in the reaction as a co-monomer and influences the nanostructure of the material. The evolution of the polymer was monitored using nuclear magnetic resonance spectroscopy and the structure of the resulting organic aerogels depending on the molar ratio of 5-methylresorcinol to 2,6-dihydroxy-4-methyl benzoic acid was studied by nitrogen adsorption–desorption measurements, scanning electron microscopy and infrared spectrometry.

Theoretical prediction and assignment of vicinal 1H-1H coupling constants of diastereomeric 3-alkoxy-6,7-epoxy-2-oxabicyclo[3.3.0]octanes.

Spin–spin coupling constants between nuclei in NMR spectroscopy reflect their spatial arrangement. A number of calculation methods, applying different levels of theory, have been developed to support the stereochemical assignment of novel compounds. Nevertheless, revisions of the assignment of structures in the literature are not rare. In the present work, the reliability of the calculation methods amenable for a theoretical prediction of spin–spin coupling constants of vicinal protons to support correct stereochemical assignment of substitution at five‐membered rings of 3‐alkoxy‐6,7‐epoxy‐2‐oxabicyclo[3.3.0]octanes was studied. Experimental 3J(H,H) coupling constants were compared with the coupling constants calculated for all possible diastereomers. The fully quantum chemical approach provided theoretical 3J(H,H) coupling constants with an absolute deviation of no more than 1.1 Hz for 91% of the experimentally studied coupled spins, whereas the methods without quantum chemical geometry optimization resulted in completely unreliable predictions. Consequently, for a reliable stereochemical assignment of small and medium size molecules, the protocol for calculating the coupling constants based on the results of the quantum chemical geometry optimization is recommended. Copyright

rac-8a’-Methyl-3′,4′,8′,8a’-tetra­hydro-2′H-spiro­[[1,3]dioxolane-2,1′-naphthalen]-6′(7′H)-one

The title racemic compound, C13H18O3, a common precursor in the total synthesis of terpenes, crystallizes with two molecules in the asymmetric unit. The crystal structure is made up of triple chains, formed by weak intermolecular C—H⋯O contacts, propagating in the a-axis direction.

A quantitative method for analysis of mixtures of homologues and stereoisomers of hemicucurbiturils that allows us to follow their formation and stability

Hemicucurbiturils are a sub-group of macrocyclic compounds within the cucurbit[n]uril family. The ability of unsubstituted and substituted hemicucurbiturils to form host–guest complexes allows selective binding of anions, application in catalysis and chiral discrimination between enantiomeric guests. Herein we demonstrate the separation of hemicucurbituril homologues and diastereomers by reverse phase HPLC and the quantitative analysis of hemicucurbit[6]uril, (all-R,R)-cyclohexanohemicucurbit[6]uril, (all-R,S)-cyclohexanohemicucurbit[6]uril and (all-R,R)-cyclohexanohemicucurbit[8]uril. The applicability of the developed quantitative analysis is demonstrated by the estimation of the reaction yields of cyclohexanohemicucurbiturils and by following the depolymerisation of hemicucurbit[6]uril under acidic conditions. Analysis of the studied set of compounds – monomers, oligomers and macrocycles – reveals that the number of repeating units and UV extinction coefficients are not proportional; also, the UV absorbance of a macrocycle is 10-fold higher compared to its linear isomer. The possibility of a drastic difference in the ultraviolet absorbance of oligomeric analogues should also be considered in quantification of other classes of polymeric macrocycles.

Cucurbiturils: Synthesis, Structures, Formation Mechanisms, and Nomenclature

The cucurbituril (CB) family has grown exponentially during the past two decades due to its exceptional binding ability and wide possibilities for applications. This article focuses on the description of the currently known core cucurbiturils, with the objective of bringing their homologues and derivatives under a unified nomenclature. An overview of the CB formation mechanisms, which follow the principles of dynamic covalent chemistry, is given, and synthetic methods used in cucurbituril chemistry are covered. Based on their crystal structures, a comparison of the dimensions and shapes of cucurbituril derivatives is made, and their known solubilities in water are also listed.

Methylphosphonic acid as a 31P-NMR standard for the quantitative determination of phosphorus in carbonated beverages

Methylphosphonic acid (MPA) is introduced as an internal standard for the determination of the phosphorus content of carbonated beverages (cola drinks) by quantitative 31P-NMR analysis. Phosphorus in cola beverages was analyzed as phosphate in ten commercially available drinks. Phosphate concentration in the studied samples was in the range of 3.5 to 6.1 mM. The preparation of the samples included: degassing of commercially available beverages, addition of MPA as an internal standard, D2O for signal locking and a solution of NaOH to ensure a basic environment in the sample. The calibration graphs of the MPA standard and analyte showed a linear response in the concentration range of interest. The measured values of the phosphoric acid standard solutions lay within the confidence limits of the MPA, showing that these compounds give a similar response in NMR analysis. The measured concentrations of phosphorus were in good agreement with the values detected by the traditional spectrophotometric method. The presented 31P-NMR method using MPA as an internal standard is reliable and simple for the determination of the phosphorus content of cola type beverages.

Unexpected Reactivity of Ethyl 2-(Diethylphosphono)Propionate Toward 2,2-Disubstituted-1,3-cyclopentanediones

Abstract A Horner-Wadsworth-Emmons reagent-ethyl 2-(diethylphosphono)propionate in the reaction with 2,2-disubstituted-1,3-cyclopentanediones, results in 4-oxohexanoic acid ethyl ester derivative up to 90% isolated yield. 31P-13C- and 1H-NMR study of the intermediates of the reaction involving the ethyl 2-(diethylphosphono)propionate was accomplished.