The synthesis, crystal structure and Hirshfeld analysis of 4-(3,4-di-methyl-anilino)-N-(3,4-di-methyl-phen-yl)quinoline-3-carboxamide.

The structure of the title quinoline carboxamide derivative, C26H25N3O, is described. The quinoline moiety is not planar as a result of a slight puckering of the pyridine ring. The secondary amine has a slightly pyramidal geometry, certainly not planar. Both intra- and inter-molecular hydrogen bonds are present. Hirshfeld surface analysis and lattice energies were used to investigate the inter-molecular inter-actions.

Erratum: Crystal structures and Hirshfeld surface analyses of (E)-N'-benzyl-idene-2-oxo-2H-chromene-3-carbo-hydrazide and the disordered hemi-DMSO solvate of (E)-2-oxo-N'-(3,4,5-trimeth-oxybenzyl-idene)-2H-chromene-3-carbohydrazide: lattice energy and inter-molecular inter-action energy calculations for the former. Corrigendum.

[This corrects the article DOI: 10.1107/S2056989019012015.].

Crystal structure, Hirshfeld surface analysis and PIXEL calculations of a 1:1 epimeric mixture of 3-[(4-nitro-benzyl-idene)amino]-2(R,S)-(4-nitro-phenyl)-5(S)-(propan-2-yl)imidazolidin-4-one.

A 1:1 epimeric mixture of 3-[(4-nitro-benzyl-idene)amino]-2(R,S)-(4-nitro-phen-yl)-5(S)-(propan-2-yl)imidazolidin-4-one, C19H19N5O5, was isolated from a reaction mixture of 2(S)-amino-3-methyl-1-oxo-butane-hydrazine and 4-nitro-benz-alde-hyde in ethanol. The product was derived from an initial reaction of 2(S)-amino-3-methyl-1-oxo-butane-hydrazine at its hydrazine group to provide a 4-nitro-benzyl-idene derivative, followed by a cyclization reaction with another mol-ecule of 4-nitro-benzaldehyde to form the chiral five-membered imidazolidin-4-one ring. The formation of the five-membered imidazolidin-4-one ring occurred with retention of the configuration at the 5-position, but with racemization at the 2-position. In the crystal, N-H⋯O(nitro) hydrogen bonds, weak C-H⋯O(carbon-yl) and C-H⋯O(nitro) hydrogen bonds, as well as C-H⋯π, N-H⋯π and π-π inter-actions, are present. These combine to generate a three-dimensional array. Hirshfeld surface analysis and PIXEL calculations are also reported.

Crystal structures and Hirshfeld surface analyses of (E)-N'-benzyl-idene-2-oxo-2H-chromene-3-carbo-hydrazide and the disordered hemi-DMSO solvate of (E)-2-oxo-N'-(3,4,5-trimeth-oxybenzyl-idene)-2H-chromene-3-carbohydrazide: lattice energy and inter-molecular inter-action energy calculations for the former.

The crystal structures of the disordered hemi-DMSO solvate of (E)-2-oxo-N'-(3,4,5-tri-meth-oxy-benzyl-idene)-2H-chromene-3-carbohydrazide, C20H18N2O6·0.5C2H6OS, and (E)-N'-benzyl-idene-2-oxo-2H-chromene-3-carbohydrazide, C17H12N2O3 (4: R = C6H5), are discussed. The non-hydrogen atoms in compound [4: R = (3,4,5-MeO)3C6H2)] exhibit a distinct curvature, while those in compound, (4: R = C6H5), are essential coplanar. In (4: R = C6H5), C-H⋯O and π-π intra-molecular inter-actions combine to form a three-dimensional array. A three-dimensional array is also found for the hemi-DMSO solvate of [4: R = (3,4,5-MeO)3C6H2], in which the mol-ecules of coumarin are linked by C-H⋯O and C-H⋯π inter-actions, and form tubes into which the DMSO mol-ecules are cocooned. Hirshfeld surface analyses of both compounds are reported, as are the lattice energy and inter-molecular inter-action energy calculations of compound (4: R = C6H5).

Crystal structures and Hirshfeld surfaces of four meth-oxy-benzaldehyde oxime derivatives, 2-MeO-XC6H3C=NOH (X = H and 2-, 3- and 4-MeO): different conformations and hydrogen-bonding patterns.

The crystal structures of four (E)-meth-oxy-benzaldehyde oxime derivatives, namely (2-meth-oxy-benzaldehyde oxime, 1, 2,3-di-meth-oxy-benzaldehyde oxime, 2, 4-di-meth-oxy-benzaldehyde oxime, 3, and 2,5-di-meth-oxy-benzaldehyde oxime, 4, are discussed. The arrangements of the 2-meth-oxy group and the H atom of the oxime unit are s-cis in compounds 1-3, but in both independent mol-ecules of compound 4, the arrangements are s-trans. There is also a difference in the conformation of the two mol-ecules in 4, involving the orientations of the 2- and 5-meth-oxy groups. The primary inter-molecular O-H(oxime)⋯O(hy-droxy) hydrogen bonds generate C(3) chains in 1 and 2. In contrast, in compound 3, the O-H(oxime)⋯O(hy-droxy) hydrogen bonds generate symmetric R 2 2(6) dimers. A more complex dimer is generated in 4 from the O-H(oxime)⋯O(hy-droxy) and C-H(2-meth-oxy)⋯O(hy-droxy) hydrogen bonds. In all cases, further inter-actions, C-H⋯O and C-H⋯π or π-π, generate three-dimensional arrays. Hirshfeld surface and fingerprint analyses are discussed.

Crystal structures and Hirshfeld surface analyses of the di- and tri-hydrates of (5α,17E)-17-hydrazonoandrostan-3-ol: Significant differences in the hydrogen bonding patterns and supramolecular arrangements.

The crystal structures, Hirshfeld surface analyses and electrostatic potential surfaces of the di- and tri-hydrates of (5α,17E)-17-hydrazonoandrostan-3-ol, 3, namely [3·(H2O)2] and [3·(H2O)3], are reported. The trihydrate, isolated from a solution of 3 in moist methanol, recrystallizes in the orthorhombic space group, P212121, while that of the dihydrate, isolated from a 1:1 aqueous methanol solution, recrystallizes in the monoclinic space group, P21. The asymmetric unit of the trihydrate involves one steroid and three water molecules, while that of the dihydrate has two similar but independent steroid molecules and four hydrate molecules. Very similar conformations are found for the steroid molecules in both hydrates. As expected, the different mole ratios of water: steroid have major influences on the structures. In both cases, complex crystal structures are constructed from various classical hydrogen bonds, involving the hydrate molecules and the hydroxy and hydrazonyl moieties of the steroid. In the trihydrate, there are no direct connections between the steroid molecules, instead the water molecules link the steroid molecules, with only weak van der Waals forces between the steroid molecules. There are some direct links between the steroid molecules in the dihydrate, involving OH(steroid hydroxyl)⋯O(steroid oxo) hydrogen bonds, in a head to head fashion, and OH⋯N(hydrazonyl) hydrogen bonds, in a head to tail fashion. However, the major occurrence throughout the structure is of steroid molecules linked by water molecules.

Different classical hydrogen-bonding patterns in three salicylaldoxime derivatives, 2-HO-4-XC6H3C=NOH (X = Me, OH and MeO).

The crystal structures of three salicyaldoxime compounds, namely 2-hy-droxy-4-methyl-benzaldehyde oxime, C8H9NO2, 1, 2,4-di-hydroxy-benzaldehyde oxime, C7H7NO3, 2, and 2-hy-droxy-4-meth-oxy-benzaldehyde oxime, C8H9NO3, 3, are discussed. In each compound, the hydroxyl groups are essentially coplanar with their attached phenyl group. The inter-planar angles between the C=N-O moieties of the oxime unit and their attached phenyl rings are 0.08 (9), 1.08 (15) and 6.65 (15)° in 1, 2 and 3, respectively. In all three mol-ecules, the 2-hy-droxy group forms an intra-molecular O-H⋯N(oxime) hydrogen bond. In compound (1), inter-molecular O-H(oxime)⋯O(hydrox-yl) hydrogen bonds generate R 2 2(14) dimers, related by inversion centres. In compound 2, inter-molecular O-H(oxime)⋯O(4-hy-droxy) hydrogen bonds generate C9 chains along the b-axis direction, while O-H(4-hydrox-yl)⋯O(2-hydrox-yl) inter-actions form zigzag C6 spiral chains along the c-axis direction, generated by a screw axis at 1, y, 1/4: the combination of the two chains provides a bimolecular sheet running parallel to the b axis, which lies between 0-1/2 c and 1/2-1 c. In compound 3, similar C9 chains, along the b-axis direction are generated by O-H(oxime)⋯O(4-meth-oxy) hydrogen bonds. Further weaker, C-H⋯π (in 1), π-π (in 2) and both C-H⋯π and π-π inter-actions (in 3) further cement the three-dimensional structures. Hirshfeld surface and fingerprint analyses are discussed.

Crystal structures and Hirshfeld surface analyses of the hemi-hydrate and hemi-methanolate of 3α-hydroxy-16α-bromoandrostan-17-one, 3: Differences in supramolecular arrangements.

The crystal structures and Hirshfeld surface analyses of two hemi-solvates of 3α-hydroxy-16α-bromoandrostan-17-one, 3, namely [(3)2.(H2O)] and [(3)2.(MeOH)], are reported. Both solvates crystallize in the monoclinic space group, P21, with Z = 4.. The asymmetric unit of the hemi-hydrate [(3)2.(H2O)] contains two independent but similar steroid molecules and a water molecule, while that of the hemi-methanoate [(3)2.(MeOH)] has four similar but independent steroid molecules and two methanol molecules. Very similar conformations are found for the steroid molecules in both solvates. In both solvates, the strongest intermolecular interactions are OH···O hydrogen bonds, involving hydroxyl groups of the steroid and the solvate molecule, which result in head-to-head directly linked steroid molecules and solvate separated steroid molecules. In both cases, the oxygen atoms of the carbonyl groups of the steroids are involved in weaker CH···O hydrogen bonds which directly link steroid molecules in tail-to-tail fashions. Combinations of the hydrogen bonds, both OH···O and CH···O, result in two-molecule wide sheets in the hemi-hydrate, which are further weakly linked in the hemi--methanoate into a 3-dimensional array. Very different hydrogen bonded chains are found in the two solvates. There is a higher proportion of CH···O to OH···O hydrogen bonds in the hemi-methanoate, [8-6], compared to that in the hemi-hydrate [1-4]: this is an indication of the weaker solvating influence of methanol compared to water.

Structure of 7-hy-droxy-3-(2-meth-oxy-phen-yl)-2-tri-fluoro-meth-yl-4H-chromen-4-one.

Herein, the synthesis and crystal structure of 7-hy-droxy-3-(2-meth-oxy-phen-yl)-2-tri-fluoro-meth-yl-4H-chromen-4-one, C17H11F3O4, are reported. This isoflavone is used as a starting material in the preparation an array of potent and competitive FPR antagonists. The pyran ring significantly deviates from planarity and the dihedral angle between the benzo-pyran mean plane and that of the exocyclic benzene ring is 88.18 (4)°. In the crystal, O-H⋯O hydrogen bonds connect the mol-ecules into C(8) chains propagating in the [010] direction.

Polymorphism in the structure of N-(5-methyl-thia-zol-2-yl)-4-oxo-4H-chromene-3-carboxamide.

Chromone derivatives have been extensively studied recently because of to their promising biological activities. The new title chromone-thia-zole hybrid presented here, C14H10N2O3S, is a candidate as a selective ligand for adenosine receptors. The compound has been synthesized and characterized by the usual spectroscopic means (NMR and EM/IE) and its structure elucidated by X-ray crystallography, which revealed the presence of packing polymorphism. The two polymorphs (one with space group P21/n and one with P21/c) show slightly different conformations and the major change induced by crystallization regards the intra-molecular contacts defining the supra-molecular structure. Those differences been highlighted by Hirshfeld surface analysis mapped over dnorm and ESP.

6-Methyl-2-oxo-N-(quinolin-6-yl)-2H-chromene-3-carboxamide: crystal structure and Hirshfeld surface analysis.

The title coumarin derivative, C20H14N2O3, displays intra-molecular N-H⋯O and weak C-H⋯O hydrogen bonds, which probably contribute to the approximate planarity of the mol-ecule [dihedral angle between the coumarin and quinoline ring systems = 6.08 (6)°]. The supra-molecular structures feature C-H⋯O hydrogen bonds and π-π inter-actions, as confirmed by Hirshfeld surface analyses.

Crystal structures of three 6-substituted coumarin-3-carboxamide derivatives.

Three coumarin derivatives, viz. 6-methyl-N-(3-methyl-phen-yl)-2-oxo-2H-chromene-3-carboxamide, C18H15NO3 (1), N-(3-meth-oxy-phen-yl)-6-methyl-2-oxo-2H-chromene-3-carboxamide, C18H15NO4 (2), and 6-meth-oxy-N-(3-meth-oxy-phen-yl)-2-oxo-2H-chromene-3-carboxamide, C18H15NO5 (3), were synthesized and structurally characterized. The mol-ecules display intra-molecular N-H⋯O and weak C-H⋯O hydrogen bonds, which probably contribute to the approximate planarity of the mol-ecules. The supra-molecular structures feature C-H⋯O hydrogen bonds and π-π inter-actions, as confirmed by Hirshfeld surface analyses.

Crystal structures of three 3,4,5-tri-meth-oxy-benzamide-based derivatives.

The crystal structures of three benzamide derivatives, viz. N-(6-hy-droxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C16H25NO5, (1), N-(6-anilinohex-yl)-3,4,5-tri-meth-oxy-benzamide, C22H30N2O4, (2), and N-(6,6-di-eth-oxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C20H33NO6, (3), are described. These compounds differ only in the substituent at the end of the hexyl chain and the nature of these substituents determines the differences in hydrogen bonding between the mol-ecules. In each mol-ecule, the m-meth-oxy substituents are virtually coplanar with the benzyl ring, while the p-meth-oxy substituent is almost perpendicular. The carbonyl O atom of the amide rotamer is trans related with the amidic H atom. In each structure, the benzamide N-H donor group and O acceptor atoms link the mol-ecules into C(4) chains. In 1, a terminal -OH group links the mol-ecules into a C(3) chain and the combined effect of the C(4) and C(3) chains is a ribbon made up of screw related R 2 (2)(17) rings in which the ⋯O-H⋯ chain lies in the centre of the ribbon and the tri-meth-oxy-benzyl groups forms the edges. In 2, the combination of the benzamide C(4) chain and the hydrogen bond formed by the terminal N-H group to an O atom of the 4-meth-oxy group link the mol-ecules into a chain of R 2 (2)(17) rings. In 3, the mol-ecules are linked only by C(4) chains.

Crystal structures of five 6-mercaptopurine derivatives.

The crystal structures of five 6-mercaptopurine derivatives, viz. 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(3-meth-oxy-phen-yl)ethan-1-one (1), C16H14N4O3S, 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-meth-oxy-phen-yl)ethan-1-one (2), C16H14N4O3S, 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-chloro-phen-yl)ethan-1-one (3), C15H11ClN4O2S, 2-[(9-acetyl-9H-purin-6-yl)sulfan-yl]-1-(4-bromo-phen-yl)ethan-1-one (4), C15H11BrN4O2S, and 1-(3-meth-oxy-phen-yl)-2-[(9H-purin-6-yl)sulfan-yl]ethan-1-one (5), C14H12N4O2S. Compounds (2), (3) and (4) are isomorphous and accordingly their mol-ecular and supra-molecular structures are similar. An analysis of the dihedral angles between the purine and exocyclic phenyl rings show that the mol-ecules of (1) and (5) are essentially planar but that in the case of the three isomorphous compounds (2), (3) and (4), these rings are twisted by a dihedral angle of approximately 38°. With the exception of (1) all mol-ecules are linked by weak C-H⋯O hydrogen bonds in their crystals. There is π-π stacking in all compounds. A Cambridge Structural Database search revealed the existence of 11 deposited compounds containing the 1-phenyl-2-sulfanyl-ethanone scaffold; of these, only eight have a cyclic ring as substituent, the majority of these being heterocycles.

Crystal structures of ethyl 6-(4-methyl-phen-yl)-4-oxo-4H-chromene-2-carboxyl-ate and ethyl 6-(4-fluoro-phen-yl)-4-oxo-4H-chromene-2-carboxyl-ate.

The crystal structures of two chromone derivatives, viz. ethyl 6-(4-methyl-phen-yl)-4-oxo-4H-chromene-2-carboxyl-ate, C19H16O4, (1), and ethyl 6-(4-fluoro-phen-yl)-4-oxo-4H-chromene-2-carboxyl-ate C18H13FO4, (2), have been determined: (1) crystallizes with two mol-ecules in the asymmetric unit. A comparison of the dihedral angles beween the mean planes of the central chromone core with those of the substituents, an ethyl ester moiety at the 2-position and a para-substituted phenyl ring at the 6-position shows that each mol-ecule differs significantly from the others, even the two independent mol-ecules (a and b) of (1). In all three mol-ecules, the carbonyl groups of the chromone and the carboxyl-ate are trans-related. The supra-molecular structure of (1) involves only weak C-H⋯π inter-actions between H atoms of the substituent phenyl group and the phenyl group, which link mol-ecules into a chain of alternating mol-ecules a and b, and weak π-π stacking inter-actions between the chromone units. The packing in (2) involves C-H⋯O inter-actions, which form a network of two inter-secting ladders involving the carbonyl atom of the carboxyl-ate group as the acceptor for H atoms at the 7-position of the chromone ring and from an ortho-H atom of the exocyclic benzene ring. The carbonyl atom of the chromone acts as an acceptor from a meta-H atom of the exocyclic benzene ring. π-π inter-actions stack the mol-ecules by unit translation along the a axis.

A comparison of the structures of some 2- and 3-substituted chromone derivatives: a structural study on the importance of the secondary carboxamide backbone for the inhibitory activity of MAO-B.

The crystal structures of the 3-substituted tertiary chromone carboxamide derivative, C17H13NO3, N-methyl-4-oxo-N-phenyl-4H-chromene-3-carboxamide (1), and the chromone carbonyl pyrrolidine derivatives, C14H13NO3, 3-(pyrrolidine-1-carbon-yl)-4H-chromen-4-one (3) and 2-(pyrrolidine-1-carbon-yl)-4H-chromen-4-one (4) have been determined. Their structural features are discussed and compared with similar compounds namely with respect to their MAO-B inhibitory activities. The chromone carboxamide presents a -syn conformation with the aromatic rings twisted with respect to each other [the dihedral angle between the mean planes of the chromone system and the exocyclic phenyl ring is 58.48 (8)°]. The pyrrolidine derivatives also display a significant twist: the dihedral angles between the chromone system and the best plane formed by the pyrrolidine atoms are 48.9 (2) and 23.97 (12)° in (3) and (4), respectively. Compound (3) shows a short C-H⋯O intra-molecular contact forming an S(7) ring. The supra-molecular structures for each compound are defined by weak C-H⋯O hydrogen bonds, which link the mol-ecules into chains and sheets. The Cambridge Structural Database gave 45 hits for compounds with a pyrrolidinecarbonyl group. A simple statistical analysis of their geometric parameters is made in order to compare them with those of the mol-ecules determined in the present work.

Crystal structures of two 6-(2-hy-droxy-benzo-yl)-5H-thia-zolo[3,2-a]pyrimidin-5-ones.

The title compounds, 6-(2-hy-droxy-benz-yl)-5H-thia-zolo[3,2-a]pyrimidin-5-one, C13H8N2O3S, (1), and 6-(2-hy-droxy-benz-yl)-3-methyl-5H-thia-zolo[3,2-a]pyrimidin-5-one, C14H10N2O3S, (2), were synthesized when a chromone-3-carb-oxy-lic acid, activated with (benzotriazol-1-yl-oxy)tripyrrolidinyl-phospho-nium hexa-fluorido-phosphate (PyBOP), was reacted with a primary heteromamine. Instead of the expected amidation, the unusual title thia-zolo-pyrimidine-5-one derivatives were obtained serendipitously and a mechanism of formation is proposed. Both compounds present an intra-molecular O-H⋯O hydrogen bond, which generates an S(6) ring. The dihedral angles between the heterocyclic moiety and the 2-hydroxybenzoyl ring are 55.22 (5) and 46.83 (6)° for (1) and (2), respectively. In the crystals, the mol-ecules are linked by weak C-H⋯O hydrogen bonds and π-π stacking inter-actions.

New insights in the discovery of novel h-MAO-B inhibitors: structural characterization of a series of N-phenyl-4-oxo-4H-chromene-3-carboxamide derivatives.

Six N-substituted-phenyl 4-oxo-4H-chromene-3-carboxamides, namely N-(2-nitro-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C16H10N2O5 (2b), N-(3-meth-oxy-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C17H13NO4, (3a), N-(3-bromo-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C16H10BrNO3, (3b), N-(4-methoxy-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C17H13NO4, (4a), N-(4-methyl-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C17H13NO3, (4d), and N-(4-hy-droxy-phen-yl)-4-oxo-4H-chromene-3-carboxamide, C16H11NO4, (4e), have been structurally characterized. All compounds exhibit an anti conformation with respect to the C-N rotamer of the amide and a trans-related conformation with the carbonyl groups of the chromone ring of the amide. These structures present an intra-molecular hydrogen-bonded network comprising an N-H⋯O hydrogen bond between the amide N atom and the O atom of the carbonyl group of the pyrone ring, forming an S(6) ring, and a weak Car-H⋯O hydrogen bond in which the carbonyl group of the amide acts as acceptor for the H atom of an ortho-C atom of the exocyclic phenyl ring, which results in another S(6) ring. The N-H⋯O intra-molecular hydrogen bond constrains the carboxamide moiety such that it is virtually coplanar with the chromone ring.