Katarzyna Ślepokura

Synthesis of pyrrolidinone derivatives from aniline, an aldehyde and diethyl acetylenedicarboxylate in an ethanolic citric acid solution under ultrasound irradiation

The ultrasound-promoted one-pot multicomponent synthesis of substituted 3-pyrrolin-2-ones using citric acid as a green additive in a green solvent is reported. Citric acid catalyzed the reaction efficiently without the need for any other harmful organic reagents. Clean reaction profile, easy work-up procedure, excellent yields and short reaction times are some remarkable features of this method. The utilization of ultrasound irradiation makes this method potentially very useful, fast, clean and convenient.

Synthesis and X-ray single crystal structure of dialkyl 2-[1-(2,2-dimethylpropionyl)-3,3-dimethyl-2-oxobutyl]-3-(triphenylphosphoranylidene)succinates

Abstract A one-pot synthesis of sterically congested phosphorus ylides in fairly high yields by the reaction of 2,2,6,6-tetramethyl-3,5-heptanedione, dialkyl acetylenedicarboxylates and triphenylphosphine is reported. The structures of these compounds were confirmed by IR, 1H, 31P and 13C NMR spectroscopy, and X-ray single crystal structure determination. The NMR spectra (CDCl3 as solvent) indicated that the compounds contained two rotamers for each ylide.

Incorporation of trinuclear lanthanide(III) hydroxo bridged clusters in macrocyclic frameworks.

A cluster of lanthanide(III) or yttrium(III) ions, Ln3(μ3-OH)2, (Ln(III) = Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Yb(III), or Y(III)) can be bound in the center of a chiral macrocyclic amines H3L1(R), H3L1(S), and H3L2(S) obtained in a reduction of a 3 + 3 condensation product of (1R,2R)- or (1S,2S)-1,2-diaminocyclohexane and 2,6-diformyl-4-methylphenol or 2,6-diformyl-4-tertbutylphenol. X-ray crystal structures of the Nd(III), Sm(III), Gd(III), Dy(III), and Y(III) complexes reveal trinuclear complexes with Ln(III) ions bridged by the phenolate oxygen atoms of the macrocycle as well as by μ3-hydroxo bridges. In the case of the Nd(III) ion, another complex form can be obtained, whose X-ray crystal structure reveals two trinuclear macrocyclic units additionally bridged by hydroxide anions, corresponding to a [Ln3(μ3-OH)]2(μ2-OH)2 cluster encapsulated by two macrocycles. The formation of trinuclear complexes is confirmed additionally by (1)H NMR, electrospray ionization mass spectrometry (ESI MS), and elemental analyses. Titrations of free macrocycles with Sm(III) or Y(III) salts and KOH also indicate that a trinuclear complex is formed in solution. On the other hand, analogous titrations with La(III) salt indicate that this kind of complex is not formed even with the excess of La(III) salt. The magnetic data for the trinuclear Gd(III) indicate weak antiferromagnetic coupling (J = -0.17 cm(-1)) between the Gd(III) ions. For the trinuclear Dy(III) and Tb(III) complexes the χ(M)T vs T plots indicate a more complicated dependence, resulting from the combination of thermal depopulation of mJ sublevels, magnetic anisotropy, and possibly weak antiferromagnetic and ferromagnetic interactions.

Cocrystals of fisetin, luteolin and genistein with pyridinecarboxamide coformers: crystal structures, analysis of intermolecular interactions, spectral and thermal characterization

Fisetin, luteolin and genistein, natural polyphenolic compounds of pharmaceutical interest, were combined with nicotinamide and isonicotinamide with an aim to obtain their cocrystals. A screening experiment utilizing solvent-drop grinding was conducted for those combinations. Cocrystalline phases were identified by XRPD and, as far as possible, obtained as single crystals in solution evaporation approach. Five new cocrystals were isolated, characterized by X-ray single-crystal diffraction, FT-Raman spectroscopy, thermal analysis (DSC and TG–DTA), 1H NMR in solution and compared in terms of supramolecular motifs. Reported herein fisetin–nicotinamide (1 : 2) ethanol hemisolvate (FisNam), fisetin–isonicotinamide (1 : 1) (FisInam), two polymorphic forms of luteolin–isonicotinamide (1 : 1) (LutInam, LutInam2) and genistein–nicotinamide (1 : 1) monohydrate (GenNam) cocrystals reveal the presence of an O–H⋯Narom heterosynthon between an O7 hydroxyl moiety of a flavonoid and the pyridyl ring of a coformer. Within those species, mutual orientations of molecules as well as flavonoid–coformer stoichiometry and solvent presence in crystal lattice are factors that imply resulting motif formation and crystal packing.

A 1:1 cocrystal of baicalein with nicotinamide.

Cocrystallization of baicalein with nicotinamide yields a 1:1 cocrystal [systematic name: pyridine-3-carboxamide-5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one (1/1)], C(6)H(6)N(2)O·C(15)H(10)O(5). The asymmetric unit contains one baicalein and one nicotinamide molecule, both in neutral forms. Molecules in the cocrystal form column motifs stabilized by an array of intermolecular hydrogen bonds.

Selective catalytic oxidation of benzyl alcohol to benzaldehyde by a mononuclear oxovanadium(V) complex of a bis(phenolate) ligand containing bulky tert-butyl substituents

A new mononuclear complex of vanadium(V), [V(O)(bp)(OCH3)] (1) has been synthesized, where H2bp is N,N′-bis(2-hydroxy-3,5-di-tert-butylbenzyl)-N′,N′-dimethylethylene-1,2-diamine. The complex was characterized by elemental analyses, spectroscopic methods and X-ray diffraction measurement. Single-crystal X-ray diffraction structure analysis of the complex revealed that the vanadium atom is octahedrally coordinated and that the bis(phenolate) ligand (bp2−) is N2O2-bonded to the vanadium(V) center in a tetradentate dinegative fashion.Graphical Abstract

Expansion of a 2 + 2 macrocycle into a 6 + 6 macrocycle: template effect of cadmium(II).

The reaction of trans-1,2-diaminocyclopentane with 2,6-diformylpyridine results in formation of 2 + 2, 3 + 3, and 4 + 4 Schiff base macrocycles as well as trace amounts of 6 + 6 and 8 + 8 macrocycles. In contrast, the 6 + 6 Schiff base macrocycle is a dominant product of the reaction of the isolated 2 + 2 macrocycle with excess of cadmium(II) chloride. The X-ray crystal structure of the protonated amine derivative of the 6 + 6 macrocycle reveals an unusual container-like conformation with the S6 axis.

Anion and Solvent Induced Chirality Inversion in Macrocyclic Lanthanide Complexes

A series of the lanthanide(III) or yttrium(III) complexes of the type [LnL(NO3)(H2O)2](NO3)2, [LnL(NO3)(H2O)](NO3)2, [LnL(H2O)2](NO3)3, and [LnLCl(H2O)2]Cl2 where L is an all-R or all-S enantiomer (L(R) or L(S)) of the chiral hexaaza macrocycle, 2(R),7(R),18(R),23(R)- or 2(S),7(S),18(S),23(S)-1,8,15,17,24,31-hexaazatricyclo[25.3.1.1.0.0]-dotriaconta-10,12,14,26,28,30-hexaene, and Ln(III) = Sm(III), Tb(III), Ho(III), Er(III), Tm(III), Yb(III), Lu(III), or Y(III), have been synthesized and structurally characterized. The crystal structure of the free macrocycle shows a highly twisted molecule, preorganized for the formation of helical complexes. The crystal structures of the lanthanide(III) complexes show two different diastereomeric forms of the macrocycle with different configurations at the stereogenic amine nitrogen atoms: (RRRR) or (RSRS) (denoted as L(RI) and L(RII), respectively). The L(RI) diastereomeric form of the nitrate derivatives [LnL(NO3)(H2O)](NO3)2 (Ln = Ho, Er) and [LnL(H2O)2](NO3)3 (Ln = Tm, Yb, Lu) convert slowly to the L(RII) form in methanol or acetonitrile solutions, while this process is not observed for the L(RI) diastereomers of analogous chloride derivatives [LnL(H2O)2]Cl3 (Ln = Tm, Yb, Lu). On the other hand, the L(RI) → L(RII) conversion for these Tm(III), Yb(III), and Lu(III) chloride derivatives can be triggered by the addition of external nitrate anions. The circular dichroism (CD) and (1)H NMR data indicate initial fast exchange of axial chloride for axial nitrate ligand, followed by slow chirality inversion of the equatorial macrocyclic ligand.

Isomorphous phosphonoacetic acid salts with magnesium(II), manganese(II), cobalt(II), zinc(II) and copper(II)

Abstract All crystals of the title compounds, with general formula M2+(C2H4O5P–)2(H2O)2, (MAP), are isomorphous and crystallize in the space group P1̅ with Z = 2. The two crystallographically independent M2+ cations are situated on a center of symmetry and are octahedrally coordinated by two phosphonate monoanions and two water molecules. In the case of Cu2+ cation, Jahn-Teller effect causes strong extension of two Cu—O bonds. The mono anions coordinate the metal ions by one carboxylic and one phosphonate oxygen atom, which is facilitated by their specific overall conformation. In each monoanion, one of the phosphonate O atoms is nearly antiperiplanar ap to the carboxylic C atom, and the remaining phosphonate O atoms are nearly gauche (+sc and –sc) with respect to the mentioned C atom. The carboxylic O atoms are in positions close to +sc and –ac in relation to the phosphonate P atom. The complex molecules form well separated layers in all MAP compounds. The phosphonate and carboxylic groups act as donors in medium strong and weak intermolecular O—H...O hydrogen bonding and, as acceptors, in C—H...O hydrogen interactions in all structures. Additionally both crystallographically independent water molecules are donors of weak hydrogen bonding to phosphonate oxygen atoms from adjacent complex molecules.

Improving solubility of fisetin by cocrystallization

Fisetin, a naturally occurring polyphenolic compound, has a proven record of in vitro demonstrated anti-carcinogenic, anti-inflammatory and antiviral properties, yet similarly to many promising APIs, its in vivo administration is complicated by low aqueous solubility and unfavourable pharmacokinetics. The presented study was focused on obtaining and characterizing cocrystals of fisetin, with the aim of improving its solubility. Solvent-drop grinding experiments, combined with FT-Raman and XRPD, were conducted to identify new cocrystalline phases, which were afterwards isolated as single-crystals and characterized structurally and in terms of thermal stability and solubility. Dissolution studies of pure fisetin and four cocrystals, namely fisetin–isonicotinamide 1 : 1 (FisInam), fisetin–nicotinamide 1 : 2 hemiethanolate (FisNam), fisetin–nicotinamide 1 : 1 (FisNam2) and fisetin–caffeine 1 : 2 (FisCaf), showed that a 2.5-fold increase of fisetin solubility was achieved for FisNam and to a smaller extent for FisCaf and FisInam (ca. 1.8- and 1.5-fold, respectively).