A structural study of 4‐aminoantipyrine and six of its Schiff base derivatives

Six derivatives of 4‐amino‐1,5‐dimethyl‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐3‐one (4‐aminoantipyrine), C₁₁H₁₃N₃O, (I), have been synthesized and structurally characterized to investigate the changes in the observed hydrogen‐bonding motifs compared to the original 4‐aminoantipyrine. The derivatives were synthesized from the reactions of 4‐aminoantipyrine with various aldehyde‐, ketone‐ and ester‐containing molecules, producing (Z)‐methyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₆H₁₉N₃O₃, (II), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₇H₂₁N₃O₃, (III), ethyl 2‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]cyclohex‐1‐enecarboxylate, C₂₀H₂₅N₃O₃, (IV), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]‐3‐phenylacrylate, C₂₂H₂₃N₃O₃, (V), 2‐cyano‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₄H₁₄N₄O₂, (VI), and (E)‐methyl 4‐{[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]methyl}benzoate, C₂₀H₁₉N₃O₃, (VII). The asymmetric units of all these compounds have one molecule on a general position. The hydrogen bonding in (I) forms chains of molecules via intermolecular N—H...O hydrogen bonds around a crystallographic sixfold screw axis. In contrast, the formation of enamines for all derived compounds except (VII) favours the formation of a six‐membered intramolecular N—H...O hydrogen‐bonded ring in (II)–(V) and an intermolecular N—H...O hydrogen bond in (VI), whereas there is an intramolecular C—H...O hydrogen bond in the structure of imine (VII). All the reported compounds, except for (II), feature π–π interactions, while C—H...π interactions are observed in (II), C—H...O interactions are observed in (I), (III), (V) and (VI), and a C—O...π interaction is observed in (II).     

Geometry and bond‐length alternation in nonlinear optical materials. II. Effects of donor strength in two push–pull molecules

The compounds N‐[2‐(4‐cyano‐5‐dicyanomethylene‐2,2‐dimethyl‐2,5‐dihydrofuran‐3‐yl)vinyl]‐N‐phenylacetamide, C₂₀H₁₆N₄O₂,(I), and 2‐{3‐cyano‐5,5‐dimethyl‐4‐[2‐(piperidin‐1‐yl)vinyl]‐2,5‐dihydrofuran‐2‐ylidene}malononitrile 0.376‐hydrate, C₁₇H₁₈N₄O·0.376H₂O, (II), are novel push–pull molecules. The significant bonding changes in the polyene chain compared with the parent molecule 2‐dicyanomethylene‐4,5,5‐trimethyl‐2,5‐dihyrofuran‐3‐carbonitrile are consistent with the relative electron‐donating properties of the acetanilido and piperidine groups. The packing of (I) utilizes one phenyl–cyano C—H...N and two phenyl–carbonyl C—H...O hydrogen bonds. Compound (II) crystallizes with a partial water molecule (0.376H₂O), consistent with cell packing that is dominated by attractive C—H...N(cyano) interactions. These compounds are precursors to novel nonlinear optical chromophores, studied to assess the impact of donor strength and the extent of conjugation on bond‐length alternation, crystal packing and aggregation.     

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.     

Six closely related 4,6‐disubstituted 2‐amino‐5‐formylpyrimidines: different ring conformations,polarized electronic structures,and hydrogen‐bonded assembly in zero,one, two and three dimensions

In each of ethyl N‐{2‐amino‐5‐formyl‐6‐[methyl(phenyl)amino]pyrimidin‐4‐yl}glycinate, C₁₆H₁₉N₅O₃, (I), N‐{2‐amino‐5‐formyl‐6‐[methyl(phenyl)amino]pyrimidin‐4‐yl}glycinamide, C₁₄H₁₆N₆O₂, (II), and ethyl 3‐amino‐N‐{2‐amino‐5‐formyl‐6‐[methyl(phenyl)amino]pyrimidin‐4‐yl}propionate, C₁₇H₂₁N₅O₃, (III), the pyrimidine ring is effectively planar, but in each of methyl N‐{2‐amino‐6‐[benzyl(methyl)amino]‐5‐formylpyrimidin‐4‐yl}glycinate, C₁₆H₁₉N₅O₃, (IV), ethyl 3‐amino‐N‐{2‐amino‐6‐[benzyl(methyl)amino]‐5‐formylpyrimidin‐4‐yl}propionate, C₁₈H₂₃N₅O₃, (V), and ethyl 3‐amino‐N‐[2‐amino‐5‐formyl‐6‐(piperidin‐4‐yl)pyrimidin‐4‐yl]propionate, C₁₅H₂₃N₅O₃, (VI), the pyrimidine ring is folded into a boat conformation. The bond lengths in each of (I)–(VI) provide evidence for significant polarization of the electronic structure. The molecules of (I) are linked by paired N—H...N hydrogen bonds to form isolated dimeric aggregates, and those of (III) are linked by a combination of N—H...N and N—H...O hydrogen bonds into a chain of edge‐fused rings. In the structure of (IV), molecules are linked into sheets by means of two hydrogen bonds, both of N—H...O type, in the structure of (V) by three hydrogen bonds, two of N—H...N type and one of C—H...O type, and in the structure of (VI) by four hydrogen bonds, all of N—H...O type. Molecules of (II) are linked into a three‐dimensional framework structure by a combination of three N—H...O hydrogen bonds and one C—H...O hydrogen bond.     

Two polymorphs and the diethylammonium salt of the barbiturate eldoral

Polymorph (Ia) of eldoral [5‐ethyl‐5‐(piperidin‐1‐yl)barbituric acid or 5‐ethyl‐5‐(piperidin‐1‐yl)‐1,3‐diazinane‐2,4,6‐trione], C₁₁H₁₇N₃O₃, displays a hydrogen‐bonded layer structure parallel to (100). The piperidine N atom and the barbiturate carbonyl group in the 2‐position are utilized in N—H...N and N—H...O=C hydrogen bonds, respectively. The structure of polymorph (Ib) contains pseudosymmetry elements. The two independent molecules of (Ib) are connected via N—H...O=C(4/6‐position) and N—H...N(piperidine) hydrogen bonds to give a chain structure in the [100] direction. The hydrogen‐bonded layers, parallel to (010), formed in the salt diethylammonium 5‐ethyl‐5‐(piperidin‐1‐yl)barbiturate [or diethylammonium 5‐ethyl‐2,4,6‐trioxo‐5‐(piperidin‐1‐yl)‐1,3‐diazinan‐1‐ide], C₄H₁₂N⁺·C₁₁H₁₆N₃O₃⁻, (II), closely resemble the corresponding hydrogen‐bonded structure in polymorph (Ia). Like many other 5,5‐disubstituted derivatives of barbituric acid, polymorphs (Ia) and (Ib) contain the R₂²(8) N—H...O=C hydrogen‐bond motif. However, the overall hydrogen‐bonded chain and layer structures of (Ia) and (Ib) are unique because of the involvement of the hydrogen‐bond acceptor function in the piperidine group.     

A convenient route to pyridones,pyrazolo[2,3‐a]pyrimidines and pyrazolo[5,1‐c]triazines incorporating antipyrine moiety

Condensation of 4‐aminoantipyrine with ethyl acetoacetate, ethyl benzoylacetate, and ethyl cyanoacetate furnished the corresponding ethyl 3‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)aminoacrylate and 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide derivatives. The aminoacrylates derivatives react with acetonitrile and sodium hydride to give 2‐amino‐6‐methyl‐1‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)‐4‐pyridone. Reaction of the cyanoacetamide derivative with dimethylformamide‐dimethylacetal (DMF‐DMA) afforded 2‐cyano‐N‐[1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐pyrazol‐4‐yl]‐2‐(N,N‐dimethylamino)methylene acetamide in high yield. Treatment of the latter with 5‐aminopyrazole derivatives afforded the corresponding pyrazolo[2,3‐a]pyrimidines. 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide also reacts with heterocyclic diazonium salts to give the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine derivatives. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:508–514, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20046     

An unusual conformation of gabapentin (Gpn) in Pyr‐Gpn‐NH‐NH‐Pyr stabilized by weak interactions

The crystal structure of N‐[(1‐{2‐oxo‐2‐[2‐(pyrazin‐2‐ylcarbonyl)hydrazin‐1‐yl]ethyl}cyclohexyl)methyl]pyrazine‐2‐carboxamide monohydrate (Pyr‐Gpn‐NN‐NH‐Pyr·H₂O), C₁₉H₂₃N₇O₃·H₂O, reveals an unusual trans–gauche (tg⁻) conformation for the gabapentin (Gpn) residue around the C^γ—C^β (θ₁) and C^β—C^α (θ₂) bonds. The molecular conformation is stabilized by intramolecular N—H...N hydrogen bonds and weak C—H...O interactions. The packing of the molecules in the crystal lattice shows a network of strong N—H...O and O—H...O hydrogen bonds together with weak C—H...O and π–π inteactions.     

A comparative experimental and theoretical investigation of hydrogen‐bond,halogen‐bond and π–π interactions in the solid‐state supramolecular assembly of 2‐ and 4‐formylphenyl arylsulfonates

To explore the operational role of noncovalent interactions in supramolecular architectures with designed topologies, a series of solid‐state structures of 2‐ and 4‐formylphenyl 4‐substituted benzenesulfonates was investigated. The compounds are 2‐formylphenyl 4‐methylbenzenesulfonate, C₁₄H₁₂O₄S, 3a , 2‐formylphenyl 4‐chlorobenzenesulfonate, C₁₃H₉ClO₄S, 3b , 2‐formylphenyl 4‐bromobenzenesulfonate, C₁₃H₉BrO₄S, 3c , 4‐formylphenyl 4‐methylbenzenesulfonate, C₁₄H₁₂O₄S, 4a , 4‐formylphenyl 4‐chlorobenzenesulfonate, 4b , C₁₃H₉ClO₄S, and 4‐formylphenyl 4‐bromobenzenesulfonate, C₁₃H₉BrO₄S, 4c . The title compounds were synthesized under basic conditions from salicylaldehyde/4‐hydroxybenzaldehydes and various aryl sulfonyl chlorides. Remarkably, halogen‐bonding interactions are found to be important to rationalize the solid‐state crystal structures. In particular, the formation of O…X (X = Cl and Br) and type I X…X halogen‐bonding interactions have been analyzed by means of density functional theory (DFT) calculations and characterized using Bader's theory of `atoms in molecules' and molecular electrostatic potential (MEP) surfaces, confirming the relevance and stabilizing nature of these interactions. They have been compared to antiparallel π‐stacking interactions that are formed between the arylsulfonates.     

Syntheses and structures of three macrocyclic supramolecular complexes and one ZnII‐containing coordination polymer generated from a semi‐rigid multidentate N‐containing ligand

Semirigid organic ligands can adopt different conformations to construct coordination polymers with more diverse structures when compared to those constructed from rigid ligands. A new asymmetric semirigid organic ligand, 4‐{2‐[(pyridin‐3‐yl)methyl]‐2H‐tetrazol‐5‐yl}pyridine ( L ), has been prepared and used to synthesize three bimetallic macrocyclic complexes and one coordination polymer, namely, bis(μ‐4‐{2‐[(pyridin‐3‐yl)methyl]‐2H‐tetrazol‐5‐yl}pyridine)bis[dichloridozinc(II)] dichloromethane disolvate, [Zn₂Cl₄(C₁₂H₁₀N₆)₂]·2CH₂Cl₂, ( I ), the analogous chloroform monosolvate, [Zn₂Cl₄(C₁₂H₁₀N₆)₂]·CHCl₃, ( II ), bis(μ‐4‐{2‐[(pyridin‐3‐yl)methyl]‐2H‐tetrazol‐5‐yl}pyridine)bis[diiodidozinc(II)] dichloromethane disolvate, [Zn₂I₄(C₁₂H₁₀N₆)₂]·2CH₂Cl₂, ( III ), and catena‐poly[[[diiodidozinc(II)]‐μ‐4‐{2‐[(pyridin‐3‐yl)methyl]‐2H‐tetrazol‐5‐yl}pyridine] chloroform monosolvate], {[ZnI₂(C₁₂H₁₀N₆)]·CHCl₃}_n, ( IV ), by solution reaction with ZnX₂ (X = Cl and I) in a CH₂Cl₂/CH₃OH or CHCl₃/CH₃OH mixed solvent system at room temperature. Complex ( I ) is isomorphic with complex ( III ) and has a bimetallic ring possessing similar coordination environments for both of the Zn^II cations. Although complex ( II ) also contains a bimetallic ring, the two Zn^II cations have different coordination environments. Under the influence of the I^? anion and guest CHCl₃ molecule, complex ( IV ) displays a significantly different structure with respect to complexes ( I )–( III ). C—H…Cl and C—H…N hydrogen bonds, and π–π stacking or C—Cl…π interactions exist in complexes ( I )–( IV ), and these weak interactions play an important role in the three‐dimensional structures of ( I )–( IV ) in the solid state. In addition, the fluorescence properties of L and complexes ( I )–( IV ) were investigated.     

Impact of the anion and chalcogen on the crystal structure and properties of 4,6‐dimethyl‐2‐pyrimido(thio)nium halides

By the reaction of urea or thiourea, acetylacetone and hydrogen halide (HF, HBr or HI), we have obtained seven new 4,6‐dimethyl‐2‐pyrimido(thio)nium salts, which were characterized by single‐crystal X‐ray diffraction, namely, 4,6‐dimethyl‐2‐oxo‐2,3‐dihydropyrimidin‐1‐ium bifluoride, C₆H₉N₂O⁺·HF₂^? or (dmpH)F₂H, 4,6‐dimethyl‐2‐oxo‐2,3‐dihydropyrimidin‐1‐ium bromide, C₆H₉N₂O⁺·Br^? or (dmpH)Br, 4,6‐dimethyl‐2‐oxo‐2,3‐dihydropyrimidin‐1‐ium iodide, C₆H₉N₂O⁺·I^? or (dmpH)I, 4,6‐dimethyl‐2‐oxo‐2,3‐dihydropyrimidin‐1‐ium iodide–urea (1/1), C₆H₉N₂O⁺·I^?·CH₄N₂O or (dmpH)I·ur, 4,6‐dimethyl‐2‐sulfanylidene‐2,3‐dihydropyrimidin‐1‐ium bifluoride–thiourea (1/1), C₆H₉N₂S⁺·HF₂^?·CH₄N₂S or (dmptH)F₂H·tu, 4,6‐dimethyl‐2‐sulfanylidene‐2,3‐dihydropyrimidin‐1‐ium bromide, C₆H₉N₂S⁺·Br^? or (dmptH)Br, and 4,6‐dimethyl‐2‐sulfanylidene‐2,3‐dihydropyrimidin‐1‐ium iodide, C₆H₉N₂S⁺·I^? or (dmptH)I. Three HCl derivatives were described previously in the literature, namely, 4,6‐dimethyl‐2‐oxo‐2,3‐dihydropyrimidin‐1‐ium chloride, (dmpH)Cl, 4,6‐dimethyl‐2‐sulfanylidene‐2,3‐dihydropyrimidin‐1‐ium chloride monohydrate, (dmptH)Cl·H₂O, and 4,6‐dimethyl‐2‐sulfanylidene‐2,3‐dihydropyrimidin‐1‐ium chloride–thiourea (1/1), (dmptH)Cl·tu. Structural analysis shows that in 9 out of 10 of these compounds, the ions form one‐dimensional chains or ribbons stabilized by hydrogen bonds. Only in one compound are parallel planes present. In all the structures, there are charge‐assisted N⁺—H…X^? hydrogen bonds, as well as weaker C_Ar⁺—H…X^? and π⁺…X^? interactions. The structures can be divided into five types according to their hydrogen‐bond patterns. All the compounds undergo thermal decomposition at relatively high temperatures (150–300 °C) without melting. Four oxopyrimidinium salts containing a π⁺…X^?…π⁺ sandwich‐like structural motif exhibit luminescent properties.     

Structural comparison of group 7 tricarbonyl complexes of 2‐{[2‐(1H‐imidazol‐4‐yl)ethyl]iminomethyl}‐5‐methylphenolate

Two tricarbonyl complexes of rhenium(I) and manganese(I) coordinated by the ligand 2‐{[2‐(1H‐imidazol‐4‐yl)ethyl]iminomethyl}‐5‐methylphenolate are reported, viz. fac‐tricarbonyl(2‐{[2‐(1H‐imidazol‐4‐yl‐κN³)ethyl]iminomethyl‐κN}‐5‐methylphenolato‐κO)rhenium(I) methanol monosolvate, [Re(C₁₆H₁₄N₃O₄)(CO)₃]·CH₃OH, (I), and fac‐tricarbonyl(2‐{[2‐(1H‐imidazol‐4‐yl‐κN³)ethyl]iminomethyl‐κN}‐5‐methylphenolato‐κO)manganese(I), fac‐[Mn(C₁₆H₁₄N₃O₄)(CO)₃], (II), display facial coordination in a distorted octahedral environment. The crystal structure of (I) is stabilized by O—H...O, N—H...O and C—H...O hydrogen‐bond interactions, while that of (II) is stabilized by N—H...O hydrogen‐bond interactions only. These interactions result in two‐dimensional networks and π–π stacking for both structures.     

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.     

Two novel organic–inorganic hybrid materials from tetrachloridometallate(II) salts and 4‐[(E)‐2‐(pyridin‐1‐ium‐2‐yl)ethenyl]pyridinium

Two organic–inorganic hybrid compounds have been prepared by the combination of the 4‐[(E)‐2‐(pyridin‐1‐ium‐2‐yl)ethenyl]pyridinium cation with perhalometallate anions to give 4‐[(E)‐2‐(pyridin‐1‐ium‐2‐yl)ethenyl]pyridinium tetrachloridocobaltate(II), (C₁₂H₁₂N₂)[CoCl₄], (I), and 4‐[(E)‐2‐(pyridin‐1‐ium‐2‐yl)ethenyl]pyridinium tetrachloridozincate(II), (C₁₂H₁₂N₂)[ZnCl₄], (II). The compounds have been structurally characterized by single‐crystal X‐ray diffraction analysis, showing the formation of a three‐dimensional network through X—H...Cl_nM⁻ (X = C, N⁺; n = 1, 2; M = Co^II, Zn^II) hydrogen‐bonding interactions and π–π stacking interactions. The title compounds were also characterized by FT–IR spectroscopy and thermogravimetric analysis (TGA).     

Three quinolone compounds featuring O...I halogen bonding

Ethyl 1‐ethyl‐6‐iodo‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylate, C₁₄H₁₄INO₃, (I), and ethyl 1‐cyclopropyl‐6‐iodo‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylate, C₁₅H₁₄INO₃, (II), have isomorphous crystal structures, while ethyl 1‐dimethylamino‐6‐iodo‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylate, C₁₄H₁₅IN₂O₃, (III), possesses a different solid‐state supramolecular architecture. In all three structures, O...I halogen‐bonding interactions connect the quinolone molecules into infinite chains parallel to the unique crystallographic b axis. In (I) and (II), these molecular chains are arranged in (101) layers, viaπ–π stacking and C—H...π interactions, and these layers are then interlinked by C—H...O interactions. The structural fragments involved in the C—H...O interactions differ between (I) and (II), accounting for the observed difference in planarity of the quinolone moieties in the two isomorphous structures. In (III), C—H...O and C—H...π interactions form (100) molecular layers, which are crosslinked by O...I and C—H...I interactions.     

The effect of bromine scanning around the phenyl group of 4‐phenylquinolone derivatives

Three quinolone compounds were synthesized and crystallized in an effort to study the structure–activity relationship of these calcium‐channel antagonists. In all three quinolones, viz. ethyl 4‐(4‐bromophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate, (I), ethyl 4‐(3‐bromophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate, (II), and ethyl 4‐(2‐bromophenyl)‐2,7,7‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate, (III), all C₂₁H₂₄BrNO₃, common structural features such as a flat boat conformation of the 1,4‐dihydropyridine (1,4‐DHP) ring, an envelope conformation of the fused cyclohexanone ring and a bromophenyl ring at the pseudo‐axial position and orthogonal to the 1,4‐DHP ring are retained. However, due to the different packing interactions in each compound, halogen bonds are observed in (I) and (III). Compound (III) crystallizes with two molecules in the asymmetric unit. All of the prepared derivatives satisfy the basic structural requirements to possess moderate activity as calcium‐channel antagonists.     

Supramolecular architectures in two 1:1 cocrystals of 5‐fluorouracil with 5‐bromothiophene‐2‐carboxylic acid and thiophene‐2‐carboxylic acid

In solid‐state engineering, cocrystallization is a strategy actively pursued for pharmaceuticals. Two 1:1 cocrystals of 5‐fluorouracil (5FU; systematic name: 5‐fluoro‐1,3‐dihydropyrimidine‐2,4‐dione), namely 5‐fluorouracil–5‐bromothiophene‐2‐carboxylic acid (1/1), C₅H₃BrO₂S·C₄H₃FN₂O₂, (I), and 5‐fluorouracil–thiophene‐2‐carboxylic acid (1/1), C₄H₃FN₂O₂·C₅H₄O₂S, (II), have been synthesized and characterized by single‐crystal X‐ray diffraction studies. In both cocrystals, carboxylic acid molecules are linked through an acid–acid R ₂²(8) homosynthon (O—H…O) to form a carboxylic acid dimer and 5FU molecules are connected through two types of base pairs [homosynthon, R ₂²(8) motif] via a pair of N—H…O hydrogen bonds. The crystal structures are further stabilized by C—H…O interactions in (II) and C—Br…O interactions in (I). In both crystal structures, π–π stacking and C—F…π interactions are also observed.     

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.     

3‐Cyano‐6‐hydroxy‐4‐methyl‐2‐pyridone: two new pseudopolymorphs and two cocrystals with products of an in situ nucleophilic aromatic substitution

Four crystal structures of 3‐cyano‐6‐hydroxy‐4‐methyl‐2‐pyridone (CMP), viz. the dimethyl sulfoxide monosolvate, C₇H₆N₂O₂·C₂H₆OS, (1), the N,N‐dimethylacetamide monosolvate, C₇H₆N₂O₂·C₄H₉NO, (2), a cocrystal with 2‐amino‐4‐dimethylamino‐6‐methylpyrimidine (as the salt 2‐amino‐4‐dimethylamino‐6‐methylpyrimidin‐1‐ium 5‐cyano‐4‐methyl‐6‐oxo‐1,6‐dihydropyridin‐2‐olate), C₇H₁₃N₄⁺·C₇H₅N₂O₂⁻, (3), and a cocrystal with N,N‐dimethylacetamide and 4,6‐diamino‐2‐dimethylamino‐1,3,5‐triazine [as the solvated salt 2,6‐diamino‐4‐dimethylamino‐1,3,5‐triazin‐1‐ium 5‐cyano‐4‐methyl‐6‐oxo‐1,6‐dihydropyridin‐2‐olate–N,N‐dimethylacetamide (1/1)], C₅H₁₁N₆⁺·C₇H₅N₂O₂⁻·C₄H₉NO, (4), are reported. Solvates (1) and (2) both contain the hydroxy group in a para position with respect to the cyano group of CMP, acting as a hydrogen‐bond donor and leading to rather similar packing motifs. In cocrystals (3) and (4), hydrolysis of the solvent molecules occurs and an in situ nucleophilic aromatic substitution of a Cl atom with a dimethylamino group has taken place. Within all four structures, an R₂²(8) N—H...O hydrogen‐bonding pattern is observed, connecting the CMP molecules, but the pattern differs depending on which O atom participates in the motif, either the ortho or para O atom with respect to the cyano group. Solvents and coformers are attached to these arrangements via single‐point O—H...O interactions in (1) and (2) or by additional R₄⁴(16) hydrogen‐bonding patterns in (3) and (4). Since the in situ nucleophilic aromatic substitution of the coformers occurs, the possible Watson–Crick C–G base‐pair‐like arrangement is inhibited, yet the cyano group of the CMP molecules participates in hydrogen bonds with their coformers, influencing the crystal packing to form chains.     

Study of the Reactivity of 6,8‐Dimethyl‐4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehyde Towards Amino‐6‐oxopyridine‐3‐carboxylate Derivatives

The condensation reactions of 6,8‐dimethyl‐4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehyde ( 1 ) with equimolar amounts of ethyl 2‐amino‐4‐(4‐chlorophenyl)‐5‐cyano‐1‐[(5,6‐diphenyl‐1,2,4‐triazin‐3‐yl)amino]‐6‐oxo‐1,6‐dihydropyridine‐3‐carboxylate ( 2 ) at different reaction conditions gave different chromanone and chromenone products 3 , 4 , 5 . Also, the condensation reactions of compound 1 with ethyl 5‐cyano‐1,2‐diamino‐4‐(3‐nitrophenyl)‐6‐oxo‐1,6‐dihydropyridine‐3‐carboxylate ( 6 ) in absolute ethanol, dry benzene, acetic acid, and/or dry xylene gave a variety of products 7 , 8 , 9 , 10 depending on the solvent used.     

Supramolecular networks in (9‐fluoro‐4H‐chromeno[4,3‐c]isoxazol‐3‐yl)methanol and its 9‐chloro analogue at 100 K

The title compounds, (9‐fluoro‐4H‐chromeno[4,3‐c]isoxazol‐3‐yl)methanol, C₁₁H₈FNO₃, (I), and (9‐chloro‐4H‐chromeno[4,3‐c]isoxazol‐3‐yl)methanol, C₁₁H₈ClNO₃, (II), crystallize in the orthorhombic space group Pbca with Z′ = 1 and the triclinic space group P with Z′ = 6, respectively. The simple replacement of F by Cl in the main molecular scaffold of (I) and (II) results in significant differences in the intermolecular interaction patterns and a corresponding change in the point‐group symmetry from D_2h to C_i = S₂. These striking differences are manifested through the presence of C—H...F and the absence of O—H...O and C—H...O interactions in (I), and the absence of C—H...Cl and the presence of O—H...O and C—H...O interactions in (II). However, the geometry of the synthons formed by the O—H...N and O—H...X (X = F or Cl) interactions observed in the constitution of the supramolecular networks of both (I) and (II) remains similar. Also, C—H...O interactions are not preferred in the presence of F in (I), while they are much preferred in the presence of Cl in (II).