Role of weak C—H…O and strong N—H…O intermolecular interactions on the high‐symmetry molecular packing of trans‐cyclohexane‐1,4‐dicarboxamide

An unpredicted fourfold screw N—H…O hydrogen bond C(4) motif in a primary dicarboxamide (trans‐cyclohexane‐1,4‐dicarboxamide, C₈H₁₄N₂O₂) was investigated by single‐crystal X‐ray diffraction and IR and Raman spectroscopies. Electron‐density topology and intermolecular energy analyses determined from ab initio calculations were employed to examine the influence of weak C—H…O hydrogen‐bond interactions on the peculiar arrangement of molecules in the tetragonal P4₃2₁2 space group. In addition, the way in which the co‐operative effects of those weak bonds might modify their relative influence on molecular packing was estimated from cluster calculations. Based on the results, a structural model is proposed which helps to rationalize the unusual fourfold screw molecular arrangement.     

The synergistic co‐operation of N—H…O=P hydrogen bonds and C—H…OX weak intermolecular interactions (X is =P or —C) in the (CH3O)2P(O)(NH–NHC6F5) amidophosphoester: a combined X‐ray crystallographic and theoretical study

The asymmetric unit of O,O′‐dimethyl [(2,3,4,5,6‐pentafluorophenyl)hydrazinyl]phosphonate, C₈H₈F₅N₂O₃P, is composed of two symmetry‐independent molecules with significant differences in the orientations of the C₆F₅ and OMe groups. In the crystal structure, a one‐dimensional assembly is mediated from classical N—H…O hydrogen bonds, which includes R₂²(8), D(2) and some higher‐order graph‐set motifs. By also considering weak C—H…O=P and C—H…O—C intermolecular interactions, a two‐dimensional network extends along the ab plane. The strengths of the hydrogen bonds were evaluated using quantum chemical calculations with the GAUSSIAN09 software package at the B3LYP/6‐311G(d,p) level of theory. The LP(O) to σ*(NH) and σ*(CH) charge‐transfer interactions were examined according to second‐order perturbation theory in natural bond orbital (NBO) methodology. The hydrogen‐bonded clusters of molecules, including N—H…O and C—H…O interactions, were constructed as input files for the calculations and the strengths of the hydrogen bonds are as follows: N—H…O [R₂²(8)] > N—H…O [D(2)] > C—H…O. The decomposed fingerprint plots show that the contribution portions of the F…H/H…F contacts in both molecules are the largest.     

Cocrystals of 1,4‐diethynylbenzene with 1,3‐diacetylbenzene and benzene‐1,4‐dicarbaldehyde exhibiting strong nonconventional alkyne–carbonyl C—H…O hydrogen bonds between the components

Weak interactions between organic molecules are important in solid‐state structures where the sum of the weaker interactions support the overall three‐dimensional crystal structure. The sp‐C—H…N hydrogen‐bonding interaction is strong enough to promote the deliberate cocrystallization of a series of diynes with a series of dipyridines. It is also possible that a similar series of cocrystals could be formed between molecules containing a terminal alkyne and molecules which contain carbonyl O atoms as the potential hydrogen‐bond acceptor. I now report the crystal structure of two cocrystals that support this hypothesis. The 1:1 cocrystal of 1,4‐diethynylbenzene with 1,3‐diacetylbenzene, C₁₀H₆·C₁₀H₁₀O₂, (1), and the 1:1 cocrystal of 1,4‐diethynylbenzene with benzene‐1,4‐dicarbaldehyde, C₁₀H₆·C₈H₆O₂, (2), are presented. In both cocrystals, a strong nonconventional ethynyl–carbonyl sp‐C—H…O hydrogen bond is observed between the components. In cocrystal (1), the C—H…O hydrogen‐bond angle is 171.8 (16)° and the H…O and C…O hydrogen‐bond distances are 2.200 (19) and 3.139 (2) Å, respectively. In cocrystal (2), the C—H…O hydrogen‐bond angle is 172.5 (16)° and the H…O and C…O hydrogen‐bond distances are 2.25 (2) and 3.203 (2) Å, respectively.     

N—H…X (X = Cl and Br) hydrogen bonds in three isomorphous 3,5‐dichloropyridinium salts

Specific short contacts are important in crystal engineering. Hydrogen bonds have been particularly successful and together with halogen bonds can be useful for assembling small molecules or ions into crystals. The ionic constituents in the isomorphous 3,5‐dichloropyridinium (3,5‐diClPy) tetrahalometallates 3,5‐dichloropyridinium tetrachloridozincate(II), (C₅H₄Cl₂N)₂[ZnCl₄] or (3,5‐diClPy)₂ZnCl₄, 3,5‐dichloropyridinium tetrabromidozincate(II), (C₅H₄Cl₂N)₂[ZnBr₄] or (3,5‐diClPy)₂ZnBr₄, and 3,5‐dichloropyridinium tetrabromidocobaltate(II), (C₅H₄Cl₂N)₂[CoBr₄] or (3,5‐diClPy)₂CoBr₄, arrange according to favourable electrostatic interactions. Cations are preferably surrounded by anions and vice versa ; rare cation–cation contacts are associated with an antiparallel dipole orientation. N—H…X (X = Cl and Br) hydrogen bonds and X …X halogen bonds compete as closest contacts between neighbouring residues. The former dominate in the title compounds; the four symmetrically independent pyridinium N—H groups in each compound act as donors in charge‐assisted hydrogen bonds, with halogen ligands and the tetrahedral metallate anions as acceptors. The M —X coordinative bonds in the latter are significantly longer if the halide ligand is engaged in a classical X …H—N hydrogen bond. In all three solids, triangular halogen‐bond interactions are observed. They might contribute to the stabilization of the structures, but even the shortest interhalogen contacts are only slightly shorter than the sum of the van der Waals radii.     

N‐tert‐Butyl‐N′‐[5‐cyano‐2‐(4‐methylphenoxy)phenylsulfonyl]urea,a new TXA2 receptor antagonist

The title compound, C₁₉H₂₁N₃O₄S, crystallizes in the space group P2/c with two molecules in the asymmetric unit. The conformation of both molecules is very similar and is mainly determined by an intramolecular N—H...O hydrogen bond between a urea N atom and a sulfonyl O atom. The O and second N atom of the urea groups are involved in dimer formation via N—H...O hydrogen bonds. The intramolecular hydrogen‐bonding motif and conformation of the C—SO₂—NH(C=O)—NH—C fragment are explored and compared using the Cambridge Structural Database and theoretical calculations. The crystal packing is characterized by π–π stacking between the 5‐cyanobenzene rings.     

Three polymorphs of 3‐(3‐phenyl‐1H‐1,2,4‐triazol‐5‐yl)‐2H‐1‐benzopyran‐2‐one formed from different solvents

The polymorphic study of 3‐(3‐phenyl‐1H‐1,2,4‐triazol‐5‐yl)‐2H‐1‐benzopyran‐2‐one, C₁₇H₁₁N₃O₂, was performed due to its potential biological activity and revealed three polymorphic modifications in the triclinic space group P, the monoclinic space group P2₁ and the orthorhombic space group Pbca. These polymorphs have a one‐column layered type of crystal organization. The strongest interactions between the molecules of the studied structures is stacking between π‐systems, while N—H…N and C—H…O hydrogen bonds link stacked columns forming layers as a secondary basic structural motif. C—H…π hydrogen bonds were observed between neighbouring layers and their role is the least significant in the formation of the crystal structure. Packing differences between the polymorphic modifications are minor and can be identified only using an analysis based on a comparison of the pairwise interaction energies.     

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.     

Structural insights into methyl‐ or methoxy‐substituted 1‐(α‐aminobenzyl)‐2‐naphthol structures: the role of C—H…π interactions

Aminobenzylnaphthols are a class of compounds containing a large aromatic molecular surface which makes them suitable candidates to study the role of C—H…π interactions. We have investigated the effect of methyl or methoxy substituents on the assembling of aromatic units by preparing and determining the crystal structures of (S,S)‐1‐{(4‐methylphenyl)[(1‐phenylethyl)amino]methyl}naphthalen‐2‐ol, C₂₆H₂₅NO, and (S,S)‐1‐{(4‐methoxyphenyl)[(1‐phenylethyl)amino]methyl}naphthalen‐2‐ol, C₂₆H₂₅NO₂. The methyl group influenced the overall crystal packing even if the H atoms of the methyl group did not participate directly either in hydrogen bonding or C—H…π interactions. The introduction of the methoxy moiety caused the formation of new hydrogen bonds, in which the O atom of the methoxy group was directly involved. Moreover, the methoxy group promoted the formation of an interesting C—H…π interaction which altered the orientation of an aromatic unit.     

How the oxazole fragment influences the conformation of the tetraoxazocane ring in a cyclohexanespiro‐3′‐(1,2,4,5,7‐tetraoxazocane): single‐crystal X‐ray and theoretical study

Single crystals of (2S,5R)‐2‐isopropyl‐5‐methyl‐7‐(5‐methylisoxazol‐3‐yl)cyclohexanespiro‐3′‐(1,2,4,5,7‐tetraoxazocane), C₁₆H₂₆N₂O₅, have been studied via X‐ray diffraction. The tetraoxazocane ring adopts a boat–chair conformation in the crystalline state, which is due to intramolecular interactions. Conformational analysis of the tetraoxazocane fragment performed at the B3LYP/6‐31G(d,2p) level of theory showed that there are three minima on the potential energy surface, one of which corresponds to the conformation realized in the solid state, but not to a global minimum. Analysis of the geometry and the topological parameters of the electron density at the (3,?1) bond critical points (BCPs), and the charge transfer in the tetraoxazocane ring indicated that there are stereoelectronic effects in the O—C—O and N—C—O fragments. There is a two‐cross hyperconjugation in the N—C—O fragment between the lone electron pair of the N atom (lpN) and the antibonding orbital of a C—O bond (σ*_C—O) and vice versa between lpO and σ*_C—N. The oxazole substituent has a considerable effect on the geometry and the topological parameters of the electron density at the (3,?1) BCPs of the tetraoxazocane ring. The crystal structure is stabilized via intermolecular C—H…N and C—H…O hydrogen bonds, which is unambiguously confirmed with PIXEL calculations, a quantum theory of atoms in molecules (QTAIM) topological analysis of the electron density at the (3,?1) BCPs and a Hirshfeld analysis of the electrostatic potential. The molecules form zigzag chains in the crystal due to intermolecular C—H…N interactions being electrostatic in origin. The molecules are further stacked due to C—H…O hydrogen bonds. The dispersion component in the total stabilization energy of the crystal lattice is 68.09%.     

N‐(4‐Bi­phenyl­yl)­urea

In the crystal structure of the title compound, C₁₃H₁₂N₂O, N—H(anti)?O hydrogen bonds produce the so‐called urea α‐network and the N—H(syn) donor forms an unconventional N—H?π hydrogen bond.     

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.     

Octyl 1‐(5‐tert‐butyl‐1H‐pyrazol‐3‐yl)‐2‐(4‐chlorophenyl)‐1H‐benzimidazole‐5‐carboxylate: complex sheets built from N—H...N,C—H...N and C—H...O hydrogen bonds

In the title compound, C₂₉H₃₅ClN₄O₂, the bond lengths provide evidence for aromatic delocalization in the pyrazole ring but bond fixation in the fused imidazole ring, and the octyl chain is folded, rather than adopting an all‐trans chain‐extended conformation. A combination of N—H...N, C—H...N and C—H...O hydrogen bonds links the molecules into sheets, in which the hydrogen bonds occupy the central layer with the tert‐butyl and octyl groups arranged on either side, such that the closest contacts between adjacent sheets involve only the octyl groups. Comparisons are made with the supramolecular assembly in some simpler analogues.     

Substituent position effect on the crystal structures of N‐phenyl‐2‐phthalimidoethanesulfonamide derivatives

In order to determine the impact of different substituents and their positions on intermolecular interactions and ultimately on the crystal packing, unsubstituted N‐phenyl‐2‐phthalimidoethanesulfonamide, C₁₆H₁₄N₂O₄S, (I), and the N‐(4‐nitrophenyl)‐, C₁₆H₁₃N₃O₆S, (II), N‐(4‐methoxyphenyl)‐, C₁₆H₁₆N₃O₆S, (III), and N‐(2‐ethylphenyl)‐, as the monohydrate, C₁₈H₁₈N₂O₄S·H₂O, (IV), derivatives have been characterized by single‐crystal X‐ray crystallography. Sulfonamides (I) and (II) have triclinic crystal systems, while (III) and (IV) are monoclinic. Although the molecules differ from each other only with respect to small substituents and their positions, they crystallized in different space groups as a result of differing intra‐ and intermolecular hydrogen‐bond interactions. The structures of (I), (II) and (III) are stabilized by intermolecular N—H…O and C—H…O hydrogen bonds, while that of (IV) is stabilized by intermolecular O—H…O and C—H…O hydrogen bonds. All four structures are of interest with respect to their biological activities and have been studied as part of a program to develop anticonvulsant drugs for the treatment of epilepsy.     

A novel hydrogen-bonding N-oxide–sulfonamide–nitro N—H…O synthon determining the architecture of benzenesulfonamide cocrystals

The structures of novel cocrystals of 4-nitropyridine N-oxide with benzenesulfonamide derivatives, namely, 4-nitrobenzenesulfonamide–4-nitropyridine N-oxide (1/1), C₅H₄N₂O₃·C₆H₆N₂O₄S, and 4-chlorobenzenesulfonamide–4-nitropyridine N-oxide (1/1), C₆H₆ClNO₂S·C₅H₄N₂O₃, are stabilized by N—H…O hydrogen bonds, with the sulfonamide group acting as a proton donor. The O atoms of the N-oxide and nitro groups are acceptors in these interactions. The latter is a double acceptor of bifurcated hydrogen bonds. Previous studies on similar crystal structures indicated competition between these functional groups in the formation of hydrogen bonds, with the priority being for the N-oxide group. In contrast, the present X-ray studies indicate the existence of a hydrogen-bonding synthon including N—H…O(N-oxide) and N—H…O(nitro) bridges. We present here a more detailed analysis of the N-oxide–sulfonamide–nitro N—H…O ternary complex with quantum theory computations and the Quantum Theory of Atoms in Molecules (QTAIM) approach. Both interactions are present in the crystals, but the O atom of the N-oxide group is found to be a more effective proton acceptor in hydrogen bonds, with an interaction energy about twice that of the nitro-group O atoms.     

N‐(4‐Nitrobenzoyl)‐N′‐phenylhydrazine: a three‐dimensional hydrogen‐bonded framework

In the title compound (systematic name: N‐anilino‐4‐nitrobenzamide), C₁₃H₁₁N₃O₃, the molecules are linked into a complex three‐dimensional framework structure by a combination of two‐centre N—H...O and C—H...O hydrogen bonds and a three‐centre N—H...(O,N) hydrogen bond.     

Cocrystals of 6‐propyl‐2‐thiouracil: N—H...O versus N—H...S hydrogen bonds

In order to investigate the relative stability of N—H...O and N—H...S hydrogen bonds, we cocrystallized the antithyroid drug 6‐propyl‐2‐thiouracil with two complementary heterocycles. In the cocrystal pyrimidin‐2‐amine–6‐propyl‐2‐thiouracil (1/2), C₄H₅N₃·2C₇H₁₀N₂OS, (I), the `base pair' is connected by one N—H...S and one N—H...N hydrogen bond. Homodimers of 6‐propyl‐2‐thiouracil linked by two N—H...S hydrogen bonds are observed in the cocrystal N‐(6‐acetamidopyridin‐2‐yl)acetamide–6‐propyl‐2‐thiouracil (1/2), C₉H₁₁N₃O₂·2C₇H₁₀N₂OS, (II). The crystal structure of 6‐propyl‐2‐thiouracil itself, C₇H₁₀N₂OS, (III), is stabilized by pairwise N—H...O and N—H...S hydrogen bonds. In all three structures, N—H...S hydrogen bonds occur only within R₂²(8) patterns, whereas N—H...O hydrogen bonds tend to connect the homo‐ and heterodimers into extended networks. In agreement with related structures, the hydrogen‐bonding capability of C=O and C=S groups seems to be comparable.     

Conversion of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones to 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones: synthesis,spectroscopic characterization and the structures of four products and one ring‐opened derivative

An efficient synthesis of 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones, involving the diazotization of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones in weakly acidic solution, has been developed and the spectroscopic characterization and crystal structures of four examples are reported. The molecules of 1‐phenylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₉N₃O₂, (I), are linked into sheets by a combination of C—H…N and C—H…O hydrogen bonds, while the structures of 1‐(2‐methylphenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₆H₁₁N₃O₂, (II), and 1‐(3‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₈ClN₃O₂, (III), each contain just one hydrogen bond which links the molecules into simple chains, which are further linked into sheets by π‐stacking interactions in (II) but not in (III). In the structure of 1‐(4‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, (IV), isomeric with (III), a combination of C—H…O and C—H…π(arene) hydrogen bonds links the molecules into sheets. When compound (II) was exposed to a strong acid in methanol, quantitative conversion occurred to give the ring‐opened transesterification product methyl 2‐[4‐hydroxy‐1‐(2‐methylphenyl)‐1H‐1,2,3‐triazol‐5‐yl]benzoate, C₁₇H₁₅N₃O₃, (V), where the molecules are linked by paired O—H…O hydrogen bonds to form centrosymmetric dimers.     

A novel tetraphenylethylene derivative: 4‐methyl‐N‐[3‐(1,2,2‐triphenylethenyl)phenyl]benzenesulfonamide with aggregation‐induced emission

The novel tetraphenylethylene derivative 4‐methyl‐N‐[3‐(1,2,2‐triphenylethenyl)phenyl]benzenesulfonamide (abbreviated as MTBF), C₃₃H₂₇NO₂S, was synthesized successfully and characterized by single‐crystal X‐ray diffraction, high‐resolution mass spectroscopy and ¹H NMR spectroscopy. MTBF crystallizes in the centrosymmetric monoclinic space group P2₁/c. In the crystal structure, the MTBF molecules are connected into a one‐dimensional band and then a two‐dimensional sheet by hydrogen bonds of the N—H…O and C—H…O types. The sheets are further linked to produce a three‐dimensional network via C—H…π interactions. The molecules aggregate via these intermolecular forces, which restrain the intramolecular motions (RIM) and decrease the energy loss in the aggregation state, so as to open the radiative channels, and thus MTBF exhibits excellent fluorescence by aggregation‐induced emission (AIE) enhancement.     

A novel tubular hydrogen‐bond pattern in a new diazaphosphole oxide: a combination of X‐ray crystallography and theoretical study of hydrogen bonds

In the structure of 2‐(4‐chloroanilino)‐1,3,2λ⁴‐diazaphosphol‐2‐one, C₁₂H₁₁ClN₃OP, each molecule is connected with four neighbouring molecules through (N—H)₂…O hydrogen bonds. These hydrogen bonds form a tubular arrangement along the [001] direction built from R ³₃(12) and R ₄³(14) hydrogen‐bond ring motifs, combined with a C (4) chain motif. The hole constructed in the tubular architecture includes a 12‐atom arrangement (three P, three N, three O and three H atoms) belonging to three adjacent molecules hydrogen bonded to each other. One of the N—H groups of the diazaphosphole ring, not co‐operating in classical hydrogen bonding, takes part in an N—H…π interaction. This interaction occurs within the tubular array and does not change the dimension of the hydrogen‐bond pattern. The energies of the N—H…O and N—H…π hydrogen bonds were studied by NBO (natural bond orbital) analysis, using the experimental hydrogen‐bonded cluster of molecules as the input file for the chemical calculations. In the ¹H NMR experiment, the nitrogen‐bound proton of the diazaphosphole ring has a high value of 17.2 Hz for the ²J _H–P coupling constant.     

N,N′‐Dicyclohexyl‐N‐[4‐(1H‐indol‐3‐yl)butanoyl]urea

The title compound, C₂₅H₃₅N₃O₂, is a novel urea derivative. Pairs of intermolecular N—H...O hydrogen bonds join the molecules into centrosymmetric R₂²(12) and R₂²(18) dimeric rings, which are alternately linked into one‐dimensional polymeric chains along the [010] direction. The parallel chains are connected via C—H...O hydrogen bonds to generate a two‐dimensional framework structure parallel to the (001) plane. The title compound was also modelled by solid‐state density functional theory (DFT) calculations. A comparison of the molecular conformation and hydrogen‐bond geometry obtained from the X‐ray structure analysis and the theoretical study clearly indicates that the DFT calculation agrees closely with the X‐ray structure.