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In view of the rise of drug-resistant tuberculosis and difficult-to-treat related diseases caused by non-tuberculous mycobacteria, there is an urgent need for antimycobacterial drug discovery. Nα-aroyl-N-aryl-phenylalanine amides (AAPs) have been identified as antimycobacterial agents and are subject to lead optimization. The aim of the present study is to evaluate the impact of N-aryl ortho cyano substitution in a lead compound on the crystal and molecular structure and its in vitro activity against Mycobacterium abscessus. The title AAP can be conveniently synthesized from N-Boc-protected d-phenylalanine in two amide coupling steps using a previously established racemization-free method. Two polymorphic forms in the solid-state are described, as discovered by X-ray and electron diffraction. The introduction of a cyano group in the ortho position of the AAP N-aryl ring, however, leads to loss of in vitro activity against M. abscessus subsp. abscessus. [ABSTRACT FROM AUTHOR]

4-(4-nitrophenyl)thiomorpholine, the title compound, has been used as a precursor for the corresponding 4-thiomorpholinoaniline, which is a useful building block in medicinal chemistry. The crystal and molecular structures of the title compound, however, have not been described thus far. We synthesized the title compound by means of a nucleophilic aromatic substitution reaction of 4-fluoronitrobenzene and thiomorpholine and structurally characterized it by X-ray crystallography, DFT calculations, and Hirshfeld surface analysis. In the crystal, the molecule exhibits an approximately CS-symmetric structure, with the nitrogen-bound 4-nitrophenyl group in a quasi axial position on the six-membered thiomorpholine ring in a low-energy chair conformation. The solid-state structure of the title compound is markedly different from that of its morpholine analogue. This can be ascribed to the formation of centrosymmetric dimers through intermolecular C–H···O weak hydrogen bonds involving the methylene groups adjacent to the sulfur atom and face-to-face aromatic stacking. [ABSTRACT FROM AUTHOR]

Betaines of squaric acid have gained research interest because of their structural and spectral properties. We elucidated the crystal and molecular structure of the triethylammonium betaine of squaric acid (1) by X-ray crystallography, IR, and NMR spectroscopy augmented by Hirshfeld surface analysis and DFT calculations. The crystal structure determination using Hirshfeld atom refinement reveals that the resonance hybrid structure with partial enolate character of the two lateral squaric acid C=O groups describes 1 best. The solid-state supramolecular structure features weak intermolecular C−H···O hydrogen bonds. The number of C=O bands in the IR spectrum in the solid-state is consistent with local C2v symmetry of the squaric acid residue in 1. The 13C NMR signals of this group in solution were assigned based on 2D NMR experiments and computational prediction using the Gauge-Independent Atom Orbital (GIAO) method. The present study provides the first structural characterization of a betaine of squaric acid containing a four-coordinate nitrogen atom directly attached to the four-membered ring. [ABSTRACT FROM AUTHOR]

Synthesis and structural characterization of two heterodinuclear ZnII-LnIII complexes with the formula [ZnLn(HL)(µ-OAc)(NO3)2(H2O)x(MeOH)1-x]NO3 · n H2O · n MeOH [Ln = Pr (1), Nd (2)] and the crystal and molecular structure of [ZnNd(HL)(µ-OAc)(NO3)2(H2O)] [ZnNd(HL)(OAc)(NO3)2(H2O)](NO3)2 · n H2O · n MeOH (3) are reported. The asymmetrical compartmental ligand (E)-2-(1-(2-((2-hydroxy-3-methoxybenzylidene)amino)-ethyl)imidazolidin-2-yl)-6-methoxyphenol (H2L) is formed from N1,N3-bis(3-methoxysalicylidene)diethylenetriamine (H2valdien) through intramolecular aminal formation, resulting in a peripheral imidazoline ring. The structures of 1–3 were revealed by X-ray crystallography. The smaller ZnII ion occupies the inner N2O2 compartment of the ligand, whereas the larger and more oxophilic LnIII ions are found in the outer O2O2' site. Synthesis and structural characterization of two heterodinuclear ZnII-LnIII complexes (Ln = Pr, Nd) bearing an asymmetrical compartmental ligand formed in situ from N1,N3-bis(3-methoxysalicylidene)diethylenetriamine (H2valdien) through intramolecular aminal formation are reported. [ABSTRACT FROM AUTHOR]

Two polymorphic forms of 1-(4-methylpyridin-2-yl)thiourea (1) and the crystal and molecular structures of the 2-aminothiazoles N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (2) and N-(4-methylpyridin-2-yl)-4-(pyrazin-2-yl)thiazol-2-amine (3), derived from 1 and the respective α-bromoketone via the Hantzsch reaction, are described. Both polymorphic forms 1α (space group P21/c, Z = 4) and 1β (space group P21/n, Z = 8) crystallize in the monoclinic system but exhibit distinctly different intermolecular hydrogen bonding patterns. Compound 2 (orthorhombic, space group Pca21, Z = 8) forms polymeric N–H⋯N hydrogen-bonded zigzag tapes in the polar crystal structure, with a significant twisting between the thiazole and pyridine rings. In contrast, the crystal structure of 3 (monoclinic, space group P21/c, Z = 4) features nearly planar centrosymmetric N–H⋯N hydrogen-bonded dimers, which are laterally joined through long C–H⋯N contacts, affording a π⋯π stacked layered structure. Two polymorphs of 1-(4-methylpyridin-2-yl)thiourea and the crystal and molecular structures of two 2-aminothiazoles, derived from 1-(4-methylpyridin-2-yl)thiourea and α-bromoketones via Hantzsch reaction, are reported. [ABSTRACT FROM AUTHOR]

8-Nitro-1,3-benzothiazin-4-ones are a promising class of new antitubercular agents, two candidates of which, namely BTZ043 and PBTZ169 (INN: macozinone), have reached clinical trials. The crystal and molecular structures of two synthetic precursors, 2-chloro-3-nitro-5-(trifluoromethyl)benzoic acid, C8H3ClF3NO4 (1), and 2-chloro-3-nitro-5-(trifluoromethyl)benzamide, C8H4ClF3N2O3 (2), are reported. In 1 and 2, the respective carboxy, carboxamide and the nitro groups are significantly twisted out of the plane of the benzene ring. In 1, the nitro group is oriented almost perpendicular to the benzene ring plane. In the crystal, 1 and 2 form O-H...O and N-H...O hydrogen-bonded dimers, respectively, which in 2 extend into primary amide tapes along the [101] direction. The trifluoromethyl group in 2 exhibits rotational disorder with an occupancy ratio of 0.876 (3):0.124 (3). [ABSTRACT FROM AUTHOR]

The crystal and molecular structures of the bio-based platform chemical furfural (1) and its derivatives furfurylamine (2), 2-furonitrile (3) and 2-methylfuran (4), which are all liquid at ambient temperature, have been determined by in situ cryocrystallography. Compound 1 crystallizes with three molecules in the asymmetric unit (Z′ = 3), which all adopt the syn conformation. Compound 2 crystallizes with two crystallographically distinct molecules in gauche and anti conformers, which are linked by N–H…N and N–H…O hydrogen bonds. The crystal structure of 3 is characterized by C–H…N interactions between C4 of the furan ring and the nitrile group. Compound 4 was found to crystallize in the non-centrosymmetric space group P42bc with a polar c axis. The molecular structures are compared with results from spectroscopic studies in the literature. Compounds 1–4 show a difference of ca. 14° between the external C–C–C and C–C–O angles to the substituent carbon atom in 2-position of the furan ring. Using this criterion as an indicator for the assignment of the oxygen atom in 2-substituted furan derivatives, a number of crystal structures in the Cambridge Structural Database (CSD) are called into question. [ABSTRACT FROM AUTHOR]

• The solid-state structures of lepidine (4-methylquinoline) and three mineral acid salts are reported. • The molecules of lepidine and the lepidinium cations in the salts are π⋅⋅⋅π-stacked in the crystal structures. • N−H⋅⋅⋅Cl or N−H⋅⋅⋅O hydrogen bonding is observed in the crystal structures of the salts. The crystal and molecular structures of free-base lepidine (4-methylquinoline, 1) and the mineral acid salts lepidinium chloride (2), nitrate (3) and dihydrogen phosphate (4) are reported. Compound 1 was studied by differential scanning calorimetry and in situ capillary cryocrystallography. In the crystal structures, the molecules of free-base lepidine in 1 and the lepidinium cations in 2 – 4 are face-to-face π⋅⋅⋅π-stacked. The quinoline nitrogen atom is not involved in directional intermolecular interactions such as weak hydrogen bonds in 1. In the salts 2 – 4 , proton transfer to the quinoline nitrogen atom and N−H⋅⋅⋅Cl (in 2) and N−H⋅⋅⋅O (in 3 and 4) hydrogen bonding is observed. Hirshfeld surface analysis reveals that lepidinium salts 2 and 3 form hydrogen-bonded dimers in the crystal and confirms that the packing of 4 is dominated by hydrogen-bonded dihydrogen phosphate anion chains. [Display omitted] [ABSTRACT FROM AUTHOR]