Weak hydrogen and halogen bonding in 4‐[(2,2‐difluoroethoxy)methyl]pyridinium iodide and 4‐[(3‐chloro‐2,2,3,3‐tetrafluoropropoxy)methyl]pyridinium iodide

To enable a comparison between a C—H…X hydrogen bond and a halogen bond, the structures of two fluorous‐substituted pyridinium iodide salts have been determined. 4‐[(2,2‐Difluoroethoxy)methyl]pyridinium iodide, C₈H₁₀F₂NO⁺·I⁻, (1), has a –CH₂OCH₂CF₂H substituent at the para position of the pyridinium ring and 4‐[(3‐chloro‐2,2,3,3‐tetrafluoropropoxy)methyl]pyridinium iodide, C₉H₉ClF₄NO⁺·I⁻, (2), has a –CH₂OCH₂CF₂CF₂Cl substituent at the para position of the pyridinium ring. In salt (1), the iodide anion is involved in one N—H…I and three C—H…I hydrogen bonds, which, together with C—H…F hydrogen bonds, link the cations and anions into a three‐dimensional network. For salt (2), the iodide anion is involved in one N—H…I hydrogen bond, two C—H…I hydrogen bonds and one C—Cl…I halogen bond; additional C—H…F and C—F…F interactions link the cations and anions into a three‐dimensional arrangement.     

Crystallographic study of self‐organization in the solid state including quasi‐aromatic pseudo‐ring stacking interactions in 1‐benzoyl‐3‐(3,4‐dimethoxyphenyl)thiourea and 1‐benzoyl‐3‐(2‐hydroxypropyl)thiourea

1‐Benzoylthioureas contain both carbonyl and thiocarbonyl functional groups and are of interest for their biological activity, metal coordination ability and involvement in hydrogen‐bond formation. Two novel 1‐benzoylthiourea derivatives, namely 1‐benzoyl‐3‐(3,4‐dimethoxyphenyl)thiourea, C₁₆H₁₆N₂O₃S, (I), and 1‐benzoyl‐3‐(2‐hydroxypropyl)thiourea, C₁₁H₁₄N₂O₂S, (II), have been synthesized and characterized. Compound (I) crystallizes in the space group P , while (II) crystallizes in the space group P 2₁/c . In both structures, intramolecular N—H…O hydrogen bonding is present. The resulting six‐membered pseudo‐rings are quasi‐aromatic and, in each case, interact with phenyl rings via stacking‐type interactions. C—H…O, C—H…S and C—H…π interactions are also present. In (I), there is one molecule in the asymmetric unit. Pairs of molecules are connected via two intermolecular N—H…S hydrogen bonds, forming centrosymmetric dimers. In (II), there are two symmetry‐independent molecules that differ mainly in the relative orientations of the phenyl rings with respect to the thiourea cores. Additional strong hydrogen‐bond donor and acceptor –OH groups participate in the formation of intermolecular N—H…O and O—H…S hydrogen bonds that join molecules into chains extending in the [001] direction.     

Intra‐ and intermolecular Se...X (X = Se,O) interactions in selenium‐containing heterocycles: 3‐benzoylimino‐5‐(morpholin‐4‐yl)‐1,2,4‐diselenazole

In the selenium‐containing heterocyclic title compound {systematic name: N‐[5‐(morpholin‐4‐yl)‐3H‐1,2,4‐diselenazol‐3‐ylidene]benzamide}, C₁₃H₁₃N₃O₂Se₂, the five‐membered 1,2,4‐diselenazole ring and the amide group form a planar unit, but the phenyl ring plane is twisted by 22.12 (19)° relative to this plane. The five consecutive N—C bond lengths are all of similar lengths [1.316 (6)–1.358 (6) Å], indicating substantial delocalization along these bonds. The Se...O distance of 2.302 (3) Å, combined with a longer than usual amide C=O bond of 2.252 (5) Å, suggest a significant interaction between the amide O atom and its adjacent Se atom. An analysis of related structures containing an Se—Se...X unit (X = Se, S, O) shows a strong correlation between the Se—Se bond length and the strength of the Se...X interaction. When X = O, the strength of the Se...O interaction also correlates with the carbonyl C=O bond length. Weak intermolecular Se...Se, Se...O, C—H...O, C—H...π and π–π interactions each serve to link the molecules into ribbons or chains, with the C—H...O motif being a double helix, while the combination of all interactions generates the overall three‐dimensional supramolecular framework.     

Crystal structures of four δ‐keto esters and a Cambridge Structural Database analysis of cyano–halogen interactions

The revived interest in halogen bonding as a tool in pharmaceutical cocrystals and drug design has indicated that cyano–halogen interactions could play an important role. The crystal structures of four closely related δ‐keto esters, which differ only in the substitution at a single C atom (by H, OMe, Cl and Br), are compared, namely ethyl 2‐cyano‐5‐oxo‐5‐phenyl‐3‐(piperidin‐1‐yl)pent‐2‐enoate, C₁₉H₂₂N₂O₃, (1), ethyl 2‐cyano‐5‐(4‐methoxyphenyl)‐5‐oxo‐3‐(piperidin‐1‐yl)pent‐2‐enoate, C₂₀H₂₄N₂O₄, (2), ethyl 5‐(4‐chlorophenyl)‐2‐cyano‐5‐oxo‐3‐(piperidin‐1‐yl)pent‐2‐enoate, C₁₉H₂₁ClN₂O₃, (3), and the previously published ethyl 5‐(4‐bromophenyl)‐2‐cyano‐5‐oxo‐3‐(piperidin‐1‐yl)pent‐2‐enoate, C₁₉H₂₁BrN₂O₃, (4) [Maurya, Vasudev & Gupta (2013). RSC Adv. 3 , 12955–12962]. The molecular conformations are very similar, while there are differences in the molecular assemblies. Intermolecular C—H...O hydrogen bonds are found to be the primary interactions in the crystal packing and are present in all four structures. The halogenated derivatives have additional aromatic–aromatic interactions and cyano–halogen interactions, further stabilizing the molecular packing. A database analysis of cyano–halogen interactions using the Cambridge Structural Database [CSD; Groom & Allen (2014). Angew. Chem. Int. Ed. 53 , 662–671] revealed that about 13% of the organic molecular crystals containing both cyano and halogen groups have cyano–halogen interactions in their packing. Three geometric parameters for the C—X...N[triple‐bond]C interaction (X = F, Cl, Br or I), viz. the N...X distance and the C—X...N and C—N...X angles, were analysed. The results indicate that all the short cyano–halogen contacts in the CSD can be classified as halogen bonds, which are directional noncovalent interactions.     

2‐Amino‐5‐iodopyridinium bromide hemihydrate and 2‐amino‐5‐iodopyridinium chloride monohydrate

The hydrobromide and hydrochloride salts of 2‐amino‐5‐iodopyridine were prepared from aqueous solutions. The hydrobromide salt, C₅H₆IN₂⁺·Br⁻·0.5H₂O, crystallizes as a hemihydrate, and exhibits hydrogen bonding and π‐stacking which stabilize the crystal structure. The hydrochloride salt, C₅H₆IN₂⁺·Cl⁻·H₂O·0.375HCl, crystallized as the hydrate and exhibits similar hydrogen bonding and π‐stacking in the lattice. The most interesting feature of the hydrochloride salt is the presence of an additional fractional HCl molecule which introduces disorder in the location of the water molecule. The additional proton from the fractional HCl molecule is accounted for by the presence of a partial hydronium ion on one of the water sites.     

Synthesis,structure and in vitro cytotoxicity testing of some 1,3,4‐oxadiazoline derivatives from 2‐hydroxy‐5‐iodobenzoic acid

The syntheses of nine new 5‐iodosalicylic acid‐based 1,3,4‐oxadiazoline derivatives starting from methyl salicylate are described. These compounds are 2‐[4‐acetyl‐5‐methyl‐5‐(3‐nitrophenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6a ), 2‐[4‐acetyl‐5‐methyl‐5‐(4‐nitrophenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6b ), 2‐(4‐acetyl‐5‐methyl‐5‐phenyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl)‐4‐iodophenyl acetate, C₁₉H₁₇IN₂O₄ ( 6c ), 2‐[4‐acetyl‐5‐(4‐fluorophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate, C₁₉H₁₆FIN₂O₄ ( 6d ), 2‐[4‐acetyl‐5‐(4‐chlorophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate, C₁₉H₁₆ClIN₂O₄ ( 6e ), 2‐[4‐acetyl‐5‐(3‐bromophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6f ), 2‐[4‐acetyl‐5‐(4‐bromophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6g ), 2‐[4‐acetyl‐5‐methyl‐5‐(4‐methylphenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6h ) and 2‐[5‐(4‐acetamidophenyl)‐4‐acetyl‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6i ). The compounds were characterized by mass, ¹H NMR and ¹³C NMR spectroscopies. Single‐crystal X‐ray diffraction studies were also carried out for 6c , 6d and 6e . Compounds 6c and 6d are isomorphous, with the 1,3,4‐oxadiazoline ring having an envelope conformation, where the disubstituted C atom is the flap. The packing is determined by C—H…O, C—H…π and I…π interactions. For 6e , the 1,3,4‐oxadiazoline ring is almost planar. In the packing, Cl…π interactions are observed, while the I atom is not involved in short interactions. Compounds 6d , 6e , 6f and 6h show good inhibiting abilities on the human cancer cell lines KB and Hep‐G2, with IC₅₀ values of 0.9–4.5 µM.     

Halogen‐ and Hydrogen‐Bonded Salts and Co‐crystals Formed from 4‐Halo‐2,3,5,6‐tetrafluorophenol and Cyclic Secondary and Tertiary Amines: Orthogonal and Non‐orthogonal Halogen and Hydrogen Bonding,and Synthetic Analogues of Halogen‐Bonded Biological Systems

Co‐crystallisation of, in particular, 4‐iodotetrafluorophenol with a series of secondary and tertiary cyclic amines results in deprotonation of the phenol and formation of the corresponding ammonium phenate. Careful examination of the X‐ray single‐crystal structures shows that the phenate anion develops a C?O double bond and that the C?C bond lengths in the ring suggest a Meissenheimer‐like delocalisation. This delocalisation is supported by the geometry of the phenate anion optimised at the MP2(Full) level of theory within the aug‐cc‐pVDZ basis (aug‐cc‐pVDZ‐PP on I) and by natural bond orbital (NBO) analyses. With sp² hybridisation at the phenate oxygen atom, there is strong preference for the formation of two non‐covalent interactions with the oxygen sp² lone pairs and, in the case of secondary amines, this occurs through hydrogen bonding to the ammonium hydrogen atoms. However, where tertiary amines are concerned, there are insufficient hydrogen atoms available and so an electrophilic iodine atom from a neighbouring 4‐iodotetrafluorophenate group forms an I???O halogen bond to give the second interaction. However, in some co‐crystals with secondary amines, it is also found that in addition to the two hydrogen bonds forming with the phenate oxygen sp² lone pairs, there is an additional intermolecular I???O halogen bond in which the electrophilic iodine atom interacts with the C?O π‐system. All attempts to reproduce this behaviour with 4‐bromotetrafluorophenol were unsuccessful. These structural motifs are significant as they reproduce extremely well, in low‐molar‐mass synthetic systems, motifs found by Ho and co‐workers when examining halogen‐bonding interactions in biological systems. The analogy is cemented through the structures of co‐crystals of 1,4‐diiodotetrafluorobenzene with acetamide and with N‐methylbenzamide, which, as designed models, demonstrate the orthogonality of hydrogen and halogen bonding proposed in Ho’s biological study.     

Hydrogen and halogen bonding in the haloetherification products in chalcone

Cooperative action of hydrogen and halogen bonding in the reaction of 3‐(3,5‐di‐tert‐butyl‐4‐hydroxyphenyl)‐1‐phenylprop‐2‐en‐1‐one with HCl or HBr in alcohol medium under microwave irradiation (20 W, 80 °C, 10 min) allows the isolation of the haloetherification products (2S,3S)‐3‐(3‐tert‐butyl‐5‐chloro‐4‐hydroxyphenyl)‐2‐chloro‐3‐ethoxy‐1‐phenylpropan‐1‐one, C₂₁H₂₄Cl₂O₃, (2S,3S)‐2‐bromo‐3‐(3‐tert‐butyl‐5‐bromo‐4‐hydroxyphenyl)‐3‐methoxy‐1‐phenylpropan‐1‐one, C₂₀H₂₂Br₂O₃, and (2S,3S)‐2‐bromo‐3‐(3‐tert‐butyl‐5‐bromo‐4‐hydroxyphenyl)‐3‐ethoxy‐1‐phenylpropan‐1‐one, C₂₁H₂₄Br₂O₃, in good yields. Both types of noncovalent interactions, e.g. hydrogen and halogen bonds, are formed to stabilize the obtained products in the solid state.     

Synthesis and crystal structure of a two‐dimensional sodium coordination polymer of 4,4′‐(diazenediyl)bis(1H‐1,2,4‐triazol‐5‐one)

The crystal engineering of coordination polymers has aroused interest due to their structural versatility, unique properties and applications in different areas of science. The selection of appropriate ligands as building blocks is critical in order to afford a range of topologies. Alkali metal cations are known for their mainly ionic chemistry in aqueous media. Their coordination number varies depending on the size of the binding partners, and on the electrostatic interaction between the ligands and the metal ions. The two‐dimensional coordination polymer poly[tetra‐μ‐aqua‐[μ₄‐4,4′‐(diazenediyl)bis(5‐oxo‐1H‐1,2,4‐triazolido)]disodium(I)], [Na₂(C₄H₂N₈O₂)(H₂O)₄]_n, (I), was synthesized from 4‐amino‐1H‐1,2,4‐triazol‐5(4H)‐one (ATO) and its single‐crystal structure determined. The mid‐point of the imino N=N bond of the 4,4′‐(diazenediyl)bis(5‐oxo‐1H‐1,2,4‐triazolide) (ZTO²⁻) ligand is located on an inversion centre. The asymmetric unit consists of one Na⁺ cation, half a bridging ZTO²⁻ ligand and two bridging water ligands. Each Na⁺ cation is coordinated in a trigonal antiprismatic fashion by six O atoms, i.e. two from two ZTO²⁻ ligands and the remaining four from bridging water ligands. The Na⁺ cation is located near a glide plane, thus the two bridging O atoms from the two coordinating ZTO²⁻ ligands are on adjacent apices of the trigonal antiprism, rather than being in an anti configuration. All water and ZTO²⁻ ligands act as bridging ligands between metal centres. Each Na⁺ metal centre is bridged to a neigbouring Na⁺ cation by two water molecules to give a one‐dimensional [Na(H₂O)₂]_n chain. The organic ZTO²⁻ ligand, an O atom of which also bridges the same pair of Na⁺ cations, then crosslinks these [Na(H₂O)₂]_n chains to form two‐dimensional sheets. The two‐dimensional sheets are further connected by intermolecular hydrogen bonds, giving rise to a stabile hydrogen‐bonded network.     

Weak hydrogen bonding and fluorous interactions in the chloride and bromide salts of 4‐[(2,2,3,3‐tetrafluoropropoxy)methyl]pyridinium

Neutralization of 4‐[(2,2,3,3‐tetrafluoropropoxy)methyl]pyridine with hydrohalo acids HX (X = Cl and Br) yielded the pyridinium salts 4‐[(2,2,3,3‐tetrafluoropropoxy)methyl]pyridinium chloride, C₉H₁₀F₄NO⁺·Cl⁻, (1), and 4‐[(2,2,3,3‐tetrafluoropropoxy)methyl]pyridinium bromide, C₉H₁₀F₄NO⁺·Br⁻, (2), both carrying a fluorous side chain at the para position of the pyridinium ring. Single‐crystal X‐ray diffraction techniques revealed that (1) and (2) are isomorphous. The halide anions accept four hydrogen bonds from N—H, ortho‐C—H and CF₂—H groups. Two cations and two anions form a centrosymmetric dimeric building block, utilizing complimentary N—H…X …H—Csp ³ connections. These dimers are further crosslinked, utilizing another complimentary Csp ²—H…X …H—Csp ² connection. The pyridinium rings are π‐stacked, forming columns running parallel to the a axis that make angles of ca 44–45° with the normal to the pyridinium plane. There are also supramolecular C—H…F—C interactions, namely bifurcated C—H…F and bifurcated C—F…H interactions; additionally, one type II C—F…F—C halogen bond has been observed.     

Effect of the position of a methoxy substituent on the antimicrobial activity and crystal structures of 4‐methyl‐1,6‐diphenylpyrimidine‐2(1H)‐selenone derivatives

Derivatives of pyrimidine‐2(1H)‐selenone are a group of compounds with very strong antimicrobial activity. In order to study the effect of the position of the methoxy substituent on biological activity, molecular geometry and intermolecular interactions in the crystal, three derivatives were prepared and evaluated with respect to their antimicrobial activities, and their crystal structures were determined by X‐ray diffraction. The investigated compounds, namely, 1‐(X‐methoxyphenyl)‐4‐methyl‐6‐phenylpyrimidine‐2(1H)‐selenones (X = 2, 3 and 4 for 1 , 2 and 3 , respectively), C₁₈H₁₆N₂OSe, showed very strong activity against selected strains of Gram‐positive bacteria and fungi. Two compounds, 1 and 2 , crystallize in the monoclinic space group P2₁/c, while 3 crystallizes in the space group P2₁/n; 1 has two molecules in the asymmetric unit and the other two ( 2 and 3 ) have one molecule. The geometries of the investigated compounds differ slightly in the mutual orientations of the aromatic and pyrimidineselenone rings. The O atom in 1 stabilizes the conformation of the molecules via intramolecular C—H…O hydrogen bonding. The packing of molecules is determined by weak C—H…N and C—H…Se intermolecular interactions and additionally in 1 and 2 by C—H…O intermolecular interactions. The introduction of the methoxy substituent results in greater selectivity of the investigated compounds.     

The synthesis,crystal structure and thermal properties of an energetic compound: the hydrated azanium salt of 3,6‐bis[(1H‐1,2,3,4‐tetrazol‐5‐yl)amino]‐1,2,4,5‐tetrazine

The energetic ionic salt bis(1‐aminoguanidin‐2‐ium) 5,5′‐[1,2,4,5‐tetrazine‐3,6‐diylbis(azanediyl)]bis(1H‐1,2,3,4‐tetrazol‐1‐ide) dihydrate, 2CH₇N₄⁺·C₄H₂N₁₄²⁻·2H₂O, (I), with a high nitrogen content, has been synthesized and examined by elemental analysis, Fourier transform IR spectrometry, ¹H NMR spectroscopy and single‐crystal X‐ray crystallography. Compound (I) crystallizes in the monoclinic space group P 2₁/c with two water molecules. However, the water molecules are disordered about an inversion centre and were modelled as half‐occupancy molecules in the structure. The crystal structure reveals a three‐dimensional network of molecules linked through N—H…N, N—H…O, O—H…N and O—H…O hydrogen bonds. Thermal decomposition was investigated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The exothermic peak temperature is 509.72 K, which indicates that hydrated salt (I) exhibits good thermal stability. Non‐isothermal reaction kinetic parameters were calculated via both the Kissinger and the Ozawa methods to yield activation energies of E _k = 239.07 kJ mol⁻¹, lgA _k = 22.79 s⁻¹ and E _O = 235.38 kJ mol⁻¹ for (I). Additionally, the thermal safety was evaluated by calculating critical temperatures and thermodynamic values, viz. T _SADT, T _TIT, T _b, ΔS ^≠, ΔH ^≠ and ΔG ^≠. The results reveal that (I) exhibits good thermal safety compared to other ion salts of 3,6‐bis[(1H‐1,2,3,4‐tetrazol‐5‐yl)amino]‐1,2,4,5‐tetrazine (BTATz).     

Crystal structures of the anhydrous and two solvated forms of methyl 4‐(4‐fluorophenyl)‐6‐methyl‐2‐oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylate

Methyl 4‐(4‐fluorophenyl)‐6‐methyl‐2‐oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylate, ( I ), was found to exhibit solvatomorphism. The compound was prepared using a classic Biginelli reaction under mild conditions, without using catalysts and in a solvent‐free environment. Single crystals of two solvatomorphs and one anhydrous form of ( I ) were obtained through various crystallization methods. The anhydrous form, C₁₃H₁₃FN₂O₃, was found to crystallize in the monoclinic space group C2/c. It showed one molecule in the asymmetric unit. The solvatomorph with included carbon tetrachloride, C₁₃H₁₃FN₂O₃·0.25CCl₄, was found to crystallize in the monoclinic space group P2/n. The asymmetric unit revealed two molecules of ( I ) and one disordered carbon tetrachloride solvent molecule that lies on a twofold axis. A solvatomorph including ethyl acetate, C₁₃H₁₃FN₂O₃·0.5C₄H₈O₂, was found to crystallize in the triclinic space group P with one molecule of ( I ) and one solvent molecule on an inversion centre in the asymmetric unit. The solvent molecules in the solvatomorphs were found to be disordered, with a unique case of crystallographically induced disorder in ( I ) crystallized with ethyl acetate. Hydrogen‐bonding interactions, for example, N—H…O=C, C—H…O=C, C—H…F and C—H…π, contribute to the crystal packing with the formation of a characteristic dimer through N—H…O=C interactions in all three forms. The solvatomorphs display additional interactions, such as C—F…N and C—Cl…π, which are responsible for their molecular arrangement. The thermal properties of the forms were analysed through differential scanning calorimetry (DSC), hot stage microscopy (HSM) and thermogravimetric analysis (TGA) experiments.     

The first example of the stereoselective synthesis and crystal structure of a spirobicycloquinazolinone based on (–)‐fenchone and anthranilamide

The possibility of a single‐stage solvent‐free stereoselective synthesis of a spirocyclic compound from the natural bicyclic monoterpenoid (?)‐fenchone and anthranilamide has been shown for the first time. The molecular and crystal structure of (1R,2S,4S)‐1,3,3‐trimethyl‐1′H‐spiro[bicyclo[2.2.1]heptane‐2,2′‐quinazolin]‐4′(3′H)‐one, C₁₇H₂₂N₂O, was established by X‐ray diffraction though the chirality was assumed via the known reactant connectivity and ¹H and ¹³C NMR spectroscopy. It has shown that in the molecule, for steric reasons, there is an elongation of the Me₂C—C(N)N bond to 1.603 (5) Å. The formation of dimers via N—H…O=C hydrogen bonds with an interaction energy of 93.30 kJ mol^?1 and through cavities (33.7% of the unit‐cell volume) was established in the packing of the molecules. There are no π‐stacking interactions in the structure.     

The conformational analyses of 2‐amino‐N‐[2‐(dimethylphenoxy)ethyl]propan‐1‐ol derivatives in different environments

Four crystal structures of 2‐amino‐N‐(dimethylphenoxyethyl)propan‐1‐ol derivatives, characterized by X‐ray diffraction analysis, are reported. The free base (R,S)‐2‐amino‐N‐[2‐(2,3‐dimethylphenoxy)ethyl]propan‐1‐ol, C₁₃H₂₁NO₂, 1 , crystallizes in the space group P2₁/n, with two independent molecules in the asymmetric unit. The hydrochloride, (S)‐N‐[2‐(2,6‐dimethylphenoxy)ethyl]‐1‐hydroxypropan‐2‐aminium chloride, C₁₃H₂₂NO₂⁺·Cl^?, 2c , crystallizes in the space group P2₁, with one cation and one chloride anion in the asymmetric unit. The asymmetric unit of two salts of 2‐picolinic acid, namely, (R,S)‐N‐[2‐(2,3‐dimethylphenoxy)ethyl]‐1‐hydroxypropan‐2‐aminium pyridine‐2‐carboxylate, C₁₃H₂₂NO₂⁺·C₆H₄NO₂^?, 1p , and (R)‐N‐[2‐(2,6‐dimethylphenoxy)ethyl]‐1‐hydroxypropan‐2‐aminium pyridine‐2‐carboxylate, C₁₃H₂₂NO₂⁺·C₆H₄NO₂^?, 2p , consists of one cation and one 2‐picolinate anion. Salt 1p crystallizes in the triclinic centrosymmetric space group P, while salt 2p crystallizes in the space group P4₁2₁2. The conformations of the amine fragments are contrasted and that of 2p is found to have an unusual antiperiplanar arrangement about the ether group. The crystal packing of 1 and 2c is dominated by hydrogen‐bonded chains, while the structures of the 2‐picolinate salts have hydrogen‐bonded rings as the major features. In both salts with 2‐picolinic acid, the specific R₁²(5) hydrogen‐bonding motif is observed. Structural studies have been enriched by the generation of fingerprint plots derived from Hirshfeld surfaces.     

Synthesis and characterization of two one‐dimensional CdII coordination polymers (CPs) with 5‐amino‐2,4,6‐tribromoisophthalic acid and flexible N‐donor bipyridyl ligands

The bromo‐substituted aromatic dicarboxylic acid 5‐amino‐2,4,6‐tribromoisophthalic acid (H₂ATBIP) was used to assemble with Cd^II ions in the presence of the N‐donor flexible bipyridyl ligands 3,3′‐(diazene‐1,2‐diyl)dipyridine (mzpy) and 1,3‐bis(pyridin‐3‐ylmethyl)urea (3bpmu), leading to the formation of two chain coordination polymers by adopting solution methods, namely, catena‐poly[[[triaqua(5‐amino‐2,4,6‐tribromoisophthalato‐κO)cadmium(II)]‐μ‐3,3′‐(diazene‐1,2‐diyl)dipyridine‐κ²N¹:N^1′] dihydrate], {[Cd(C₈H₂Br₃NO₄)(C₁₀H₈N₄)(H₂O)₃]·2H₂O}_n or {[Cd(ATBIP)(mzpy)(H₂O)₃]·2H₂O}_n, ( 1 ), and catena‐poly[[[tetraaquacadmium(II)]‐μ‐1,3‐bis(pyridin‐3‐ylmethyl)urea‐κ²N¹:N^1′‐[diaquabis(5‐amino‐2,4,6‐tribromoisophthalato‐κO)cadmium(II)]‐μ‐1,3‐bis(pyridin‐3‐ylmethyl)urea‐κ²N¹:N^1′] octahydrate], {[Cd(C₈H₂Br₃NO₄)(C₁₂H₁₂N₄O)(H₂O)₃]·4H₂O}_n or {[Cd(ATBIP)(3bpmu)(H₂O)₃]·4H₂O}_n, ( 2 ). Both complexes were characterized by FT–IR spectroscopic analysis, thermogravimetric analysis (TGA), solid‐state diffuse reflectance UV–Vis spectroscopic analysis, and single‐crystal and powder X‐ray diffraction analysis (PXRD). The mzpy and 3bpmu ligands bridge the Cd^II metal centres in ( 1 ) and ( 2 ) into one‐dimensional chains, and the ATBIP²⁻ ligands show a monodentate coordination to the Cd^II centres in both coordination polymers. A discrete water tetramer exists in ( 1 ). Within the chains of ( 1 ) and ( 2 ), there are halogen bonds between adjacent ATBIP²⁻ and mzpy or 3bpmu ligands, as well as hydrogen bonds between the ATBIP²⁻ ligands and the coordinated water molecules. With the aid of weak interactions, the structures of ( 1 ) and ( 2 ) are further extended into three‐dimensional supramolecular networks. An analysis of the solid‐state diffuse reflectance UV–Vis spectra of ( 1 ) and ( 2 ) indicates that a wide indirect band gap exists in both complexes. Complexes ( 1 ) and ( 2 ) exhibit irreversible and reversible dehydration–rehydration behaviours, respectively, and the solid‐state fluorescence properties of both complexes have been studied.     

Synthesis,crystal structure and cytotoxic activity of novel 5‐methyl‐4‐thiopyrimidine derivatives

This article presents the synthesis of three new 4‐thiopyrimidine derivatives obtained from ethyl 4‐methyl‐2‐phenyl‐6‐sulfanylpyrimidine‐5‐carboxylate as the starting material, namely, ethyl 4‐[(4‐chlorobenzyl)sulfanyl]‐6‐methyl‐2‐phenylpyrimidine‐5‐carboxylate, C₂₁H₁₉ClN₂O₂S, ( 2 ), {4‐[(4‐chlorobenzyl)sulfanyl]‐6‐methyl‐2‐phenylpyrimidin‐5‐yl}methanol, C₁₉H₁₇ClN₂OS, ( 3 ), and 4‐[(4‐chlorobenzyl)sulfanyl]‐5,6‐dimethyl‐2‐phenylpyrimidine, C₁₉H₁₇ClN₂S, ( 4 ), which vary in the substituent at the 5‐position of the pyrimidine ring. The compounds were characterized by ¹H NMR, ¹³C NMR, IR and mass spectroscopies, and also elemental analysis. The molecular structures were further studied by single‐crystal X‐ray diffraction. Compound ( 2 ) crystallizes in the space group P with one molecule in the asymmetric unit, whereas compounds ( 3 ) and ( 4 ) crystallize in the space group P2₁/c with two and one molecule, respectively, in their asymmetric units. The conformation of each molecule is best defined by the dihedral angles formed between the pyrimidine ring and the planes of the two aryl substituents attached at the 2‐ and 4‐positions. The only structural difference between the three compounds is the substituent at the 5‐position of the pyrimidine ring, but they present significantly different features in the hydrogen‐bond interactions. Compound ( 2 ) displays a one‐dimensional chain formed by hydrogen bonds and the chains are further extended into a two‐dimensional network. Molecules of ( 3 ) and ( 4 ) generate one‐dimensional chains formed through intermolecular interactions. The study examines the cytotoxicity of compounds ( 3 ) and ( 4 ) against Human umbilical vein endothelial cells (HUVEC) and HeLa, K562 and CFPAC cancer cell lines. The presence of the hydroxymethyl and methyl groups in ( 3 ) and ( 4 ), respectively, offers an interesting new insight into the structures and behaviour of these derivatives. Compound ( 4 ) was found to be nontoxic against CFPAC and HUVEC; however, it shows weak activity against the HeLa and K563 cell lines. The presence of a hydroxy group in ( 3 ) significantly increases its cytotoxicity towards both, i.e. the cancer (HeLa, K562 and CFPAC) and normal (HUVEC) cell lines.     

Influence of the position of the methyl substituent and N‐oxide formation on the geometry and intermolecular interactions of 1‐(phenoxyethyl)piperidin‐4‐ol derivatives

Aminoalkanol derivatives have attracted much interest in the field of medicinal chemistry as part of the search for new anticonvulsant drugs. In order to study the influence of the methyl substituent and N‐oxide formation on the geometry of molecules and intermolecular interactions in their crystals, three new examples have been prepared and their crystal structures determined by X‐ray diffraction. 1‐[(2,6‐Dimethylphenoxy)ethyl]piperidin‐4‐ol, C₁₅H₂₃NO₂, 1 , and 1‐[(2,3‐dimethylphenoxy)ethyl]piperidin‐4‐ol, C₁₅H₂₃NO₂, 2 , crystallize in the orthorhombic system (space groups P2₁2₁2₁ and Pbca, respectively), with one molecule in the asymmetric unit, whereas the N‐oxide 1‐[(2,3‐dimethylphenoxy)ethyl]piperidin‐4‐ol N‐oxide monohydrate, C₁₅H₂₃NO₃·H₂O, 3 , crystallizes in the monoclinic space group P2₁/c, with one N‐oxide molecule and one water molecule in the asymmetric unit. The geometries of the investigated compounds differ significantly with respect to the conformation of the O—C—C linker, the location of the hydroxy group in the piperidine ring and the nature of the intermolecular interactions, which were investigated by Hirshfeld surface and corresponding fingerprint analyses. The crystal packing of 1 and 2 is dominated by a network of O—H…N hydrogen bonds, while in 3 , it is dominated by O—H…O hydrogen bonds and results in the formation of chains.