Planarity of benzoylhydrazine–dithiocarbazoate tuberculostatics. I. N′‐Methyl‐substituted 3,4‐dichlorobenzoyl monoesters

Methyl 2‐(3,4‐dichlorobenzoyl)‐1‐methylhydrazinecarbodithioate, C₁₀H₁₀Cl₂N₂OS₂, (F1), butyl 2‐(3,4‐dichlorobenzoyl)‐1‐methylhydrazinecarbodithioate, C₁₃H₁₆Cl₂N₂OS₂, (F2), and 3,4‐dichloro‐N‐(2‐sulfanylidene‐1,3‐thiazinan‐3‐yl)benzamide, C₁₁H₁₀Cl₂N₂OS₂, (F3), were studied by X‐ray diffraction to test our hypothesis that planarity of aryloylhydrazinedithiocarbazic acid esters is a prerequisite for tuberculostatic activity. All compounds examined in this study are inactive and nonplanar due to twists along two specific bonds in the central frame of the molecules. The significant twist at the N—N bond, with an C—N—N—C(S) torsion angle of about 85°, results from repulsion caused by a methyl substituent at the N′ atom of the hydrazide group. The other twist is that within the benzoyl group at the C(O)—Ph bond, i.e. the N—C(=O)—C(phenyl)—C torsion angle: the values found in the studied structures (25–30°) are in agreement with those observed in other compounds containing a similar fragment. As some nonplanar benzoyl derivatives are active, it seems that planarity of the hydrazinedithioate fragment is more important for tuberculostatic activity than planarity of the aryloyl group.     

Planarity of benzoylthiocarbazate tuberculostatics. III. Diesters of 3‐(2‐hydroxybenzoyl)dithiocarbazic acid

Searches for new tuberculostatic agents are important considering the occurrence of drug‐resistant strains of Mycobacterium tuberculosis . The structures of three new potentially tuberculostatic compounds, namely isopropyl methyl (2‐hydroxybenzoyl)carbonohydrazonodithioate, C₁₂H₁₆N₂O₂S₂, (Z )‐benzyl methyl (2‐hydroxybenzoyl)carbonohydrazonodithioate, C₁₆H₁₆N₂O₂S₂, and dibenzyl (2‐hydroxybenzoyl)carbonohydrazonodithioate propan‐2‐ol monosolvate, C₂₂H₂₀N₂O₂S₂·C₃H₈O, were determined by X‐ray diffraction. The mutual orientation of the three main fragments of the compounds, namely an aromatic ring, a dithioester group and a hydrazide group, can influence the biological activity of the compounds. In all three of the structures studied, the C(=O)NH group is in the anti conformation. In addition, the presence of the hydroxy group in the ortho position of the aromatic ring in all three structures leads to the formation of an intramolecular hydrogen bond stabilizing the planarity of the molecules.     

Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity. III. Mono‐ and diesters of 3‐(pyrazin‐2‐ylcarbonyl)dithiocarbazic acid

Methyl 2‐(pyrazin‐2‐ylcarbonyl)hydrazinecarbodithioate, C₇H₈N₄OS₂, (E1), N′‐[bis(methylsulfanyl)methylidene]pyrazine‐2‐carbohydrazide, C₈H₁₀N₄OS₂, (F1), N′‐[bis(methylsulfanyl)methylidene]‐6‐methoxypyrazine‐2‐carbohydrazide, C₉H₁₂N₄O₂S₂, (F2), and methyl 1‐methyl‐2‐(pyrazin‐2‐ylcarbonyl)hydrazinecarbodithioate, C₈H₁₀N₄OS₂, (G1), can be considered as derivatives of classical (thio)amide‐type tuberculostatics, and all are moderately active against Mycobacterium tuberculosis. This study was undertaken in a search for relationships between activity and specific intramolecular interactions, especially conjugations and hydrogen‐bond contacts, and the molecular structures were compared with respective amine analogues, also active against the pathogen. Despite the differences between the amine and carbonyl groups with opposite functions in the hydrogen bond, the two types of structure show a surprisingly similar planar geometry, mostly due to the conjugations aided by the bifurcated intramolecular hydrogen‐bond contact between the N—H group of the central hydrazide group as donor and a pyrazine N atom and an S atom of the dithio function as acceptors. Planarity was suggested to be crucial for the tuberculostatic activity of these compounds. The N‐methylated derivative (G1) showed a significant twist at the N—N bond [torsion angle = −121.9 (3)°] due to the methyl substitution, which precludes an intramolecular N—H...S contact and the planarity of the whole molecule. Nonetheless, the compound shows moderate tuberculostatic activity.     

Planarity of benzoyldithiocarbazate tuberculostatics. II. Diesters of benzoyldithiocarbazic acid

The emergence of drug‐resistant strains of Mycobacterium tuberculosis has intensified efforts to identify new lead tuberculostatics. Our earlier studies concluded that the planarity of a molecule correlates well with its tuberculostatic activity. According to our hypothesis, only derivatives whose molecules are capable of adopting a planar conformation may show tuberculostatic activity. The structures of three new potentially tuberculostatic compounds, namely N′‐[bis(methylsulfanyl)methylidene]‐N‐methyl‐4‐nitrobenzohydrazide (denoted G1), C₁₁H₁₃N₃O₃S₂, N′‐[bis(benzylsulfanyl)methylidene]‐N‐methyl‐4‐nitrobenzohydrazide (denoted G2), C₂₃H₂₁N₃O₃S₂, and N′‐[(benzylsulfanyl)(methylsulfanyl)methylidene]‐4‐nitrobenzohydrazide (denoted G3), C₁₆H₁₅N₃O₃S₂, were determined by X‐ray diffraction. The significant distortion from planarity caused by the methyl substituent at the N atom of the hydrazide group or the NO₂ substituent in the aromatic ring leads to the loss of tuberculostatic activity for G1, G2 and G4 {systematic name: N′‐[bis(methylsulfanyl)methylidene]‐2‐nitrobenzohydrazide}. A similar effect is observed when there are large substituents at the S atoms (G2 and G3).     

The influence of sulfur substituents on the molecular geometry and packing of thio derivatives of N‐methylphenobarbital

The room‐temperature crystal structures of four new thio derivatives of N‐methylphenobarbital [systematic name: 5‐ethyl‐1‐methyl‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trione], C₁₃H₁₄N₂O₃, are compared with the structure of the parent compound. The sulfur substituents in N‐methyl‐2‐thiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐2‐thioxo‐1,2‐dihydropyrimidine‐4,6(3H,5H)‐dione], C₁₃H₁₄N₂O₂S, N‐methyl‐4‐thiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐4‐thioxo‐3,4‐dihydropyrimidine‐2,6(1H,5H)‐dione], C₁₃H₁₄N₂O₂S, and N‐methyl‐2,4,6‐trithiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trithione], C₁₃H₁₄N₂S₃, preserve the heterocyclic ring puckering observed for N‐methylphenobarbital (a half‐chair conformation), whereas in N‐methyl‐2,4‐dithiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidine‐6(5H)‐one], C₁₃H₁₄N₂OS₂, significant flattening of the ring was detected. The number and positions of the sulfur substituents influence the packing and hydrogen‐bonding patterns of the derivatives. In the cases of the 2‐thio, 4‐thio and 2,4,6‐trithio derivatives, there is a preference for the formation of a ring motif of the R₂²(8) type, which is also a characteristic of N‐methylphenobarbital, whereas a C(6) chain forms in the 2,4‐dithio derivative. The preferences for hydrogen‐bond formation, which follow the sequence of acceptor position 4 > 2 > 6, confirm the differences in the nucleophilic properties of the C atoms of the heterocyclic ring and are consistent with the course of N‐methylphenobarbital thionation reactions.     

The crystal structure of 9‐chloro‐4,5‐dihydro‐2‐ethyl‐1‐(2,4,6‐trichlorophenyl)‐1H‐1,2,4‐triazolo[3,2‐d][1,5]‐benzoxazepinium hexachloroantimonate

The title compound 4 , i.e. 9‐chloro‐4,5‐dihydro‐2‐ethyl‐1‐(2,4,6‐trichlorophenyl)‐1H‐1,2,4‐triazolo[3,2‐d]‐[1,5]benzoxazepinium hexachloroantimonate, is a novel 6‐7‐5 tricyclic heterocycle. C₁₈H₁₄Cl₄N₃O·SbCJ₆, M = 764.61, P2₁/c(#14), a = 13.457(4), b = 11.583(2), c = 18.992(3) Å α = 90, β = 110.11(1)°, Z = 4, V = 2780(1) ų, D_c = 1.827 g/cc, μ (MoKα) = 19.69 cm^?1, F(000) = 1488.00, T = 293 K, R_int = 0.055 for 3094 independent reflections with I>3.00σ(I). The five‐membered heterocyclic ring is nearly planar, with the trichlorophenyl ring at N(2) almost perpendicular to it. However, the seven‐membered ring is not planar, but adopts a twist‐boat conformation.     

Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity. II. Crystal structures of 3‐[amino(pyrazin‐2‐yl)methylidene]‐2‐methylcarbazic acid esters

Four compounds showing moderate antituberculostatic activity have been studied to test the hypothesis that the planarity of the 2‐[amino(pyrazin‐2‐yl)methylidene]dithiocarbazate fragment is crucial for activity. N′‐Anilinopyrazine‐2‐carboximidamide, C₁₁H₁₁N₅, D1, and diethyl 2,2′‐[({[amino(pyrazin‐2‐yl)methylidene]hydrazinylidene}methylidene)bis(sulfanediyl)]diacetate, C₁₄H₁₉N₅O₄S₂, B1, maintain planarity due to conjugation and attractive intramolecular hydrogen‐bond contacts, while methyl 3‐[amino(pyrazin‐2‐yl)methylidene]‐2‐methyldithiocarbazate, C₈H₁₁N₅S₂, C1, and benzyl 3‐[amino(pyrazin‐2‐yl)methylidene]‐2‐methyldithiocarbazate, C₁₄H₁₅N₅S₂, C2, are not planar, due to methylation at one of the N atoms of the central N—N bond. The resulting twists of the two molecular halves (parts) of C1 and C2 are indicated by torsion angles of 116.5 (2) and −135.9 (2)°, respectively, compared with values of about 180° in the crystal structures of nonsubstituted compounds. As the methylated derivatives show similar activity against Mycobacterium tuberculosis to that of the nonsubstituted derivatives, maintaining planarity does not seem to be a prerequisite for activity.     

Five related N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamides

In the solid state, 4‐methoxy‐N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₁₀H₁₀Cl₃N₃O, (I), N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₉H₈Cl₃N₃, (II), 4‐chloro‐N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₉H₇Cl₄N₃, (III), 4‐bromo‐N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₉H₇BrCl₃N₃, (IV), and 4‐trifluoromethyl‐N′‐(2,2,2‐trichloroethanimidoyl)benzene‐1‐carboximidamide, C₁₀H₇Cl₃F₃N₃, (V), display strong intramolecular N—H...N hydrogen bonding across the chelate ring and also intramolecular N—H...Cl contacts. Additional intermolecular hydrogen bonds link the molecules into chains, double chains or sheets in all cases except for compound (V). For compound (II), there are three independent molecules per asymmetric unit.     

Twist‐chair conformation of the tetraoxepane ring remains unchanged in tetraoxaspirododecane diamines

A detailed structural analysis has been performed for N,N′‐bis(4‐chlorophenyl)‐7,8,11,12‐tetraoxaspiro[5.6]dodecane‐9,10‐diamine, C₂₀H₂₂Cl₂N₂O₄, (I), N,N′‐bis(2‐fluorophenyl)‐7,8,11,12‐tetraoxaspiro[5.6]dodecane‐9,10‐diamine, C₂₀H₂₂F₂N₂O₄, (II), and N,N′‐bis(4‐fluorophenyl)‐7,8,11,12‐tetraoxaspiro[5.6]dodecane‐9,10‐diamine, C₂₀H₂₂F₂N₂O₄, (III). The seven‐membered ring with two peroxide groups adopts a twist‐chair conformation in all three compounds. The lengths of the C—N and O—O bonds are slightly shorter than the average statistical values found in the literature for azepanes and 1,2,4,5‐tetraoxepanes. The geometry analysis of compounds (I)–(III), the topological analysis of the electron density at the (3, ?1) bond critical points within Bader's quantum theory of `Atoms in molecules' (QTAIM) and NBO (natural bond orbital) analysis at the B3LYP/6‐31G(d,2p) level of theory showed that there are n_O→σ*(C—O), n_N→σ*(C—O) and n_O→σ*(C—N) stereoelectronic effects. The molecules of compounds (I) and (III) are packed in the crystals as zigzag chains due to strong N—H…O and C—H…O hydrogen‐bond interactions, whereas the molecules of compound (II) form chains in the crystals bound by N—H…O, C—H…π and C—H…O contacts. All these data show that halogen atoms and their positions have a minimal effect on the geometric parameters, stereoelectronic effects and crystal packing of compounds (I)–(III), so that the twist‐chair conformation of the tetraoxepane ring remains unchanged.     

Eight 7‐benzyl‐3‐tert‐butyl‐1‐phenylpyrazolo[3,4‐d]oxazines,encompassing structures containing no intermolecular hydrogen bonds,and hydrogen‐bonded structures in one,two or three dimensions

7‐Benzyl‐3‐tert‐butyl‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₂H₂₅N₃O, (I), and 3‐tert‐butyl‐7‐(4‐methylbenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₇N₃O, (II), are isomorphous in the space group P2₁, and molecules are linked into chains by C—H...O hydrogen bonds. In each of 3‐tert‐butyl‐7‐(4‐methoxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₇N₃O₂, (III), which has cell dimensions rather similar to those of (I) and (II), also in P2₁, and 3‐tert‐butyl‐1‐phenyl‐7‐[4‐(trifluoromethyl)benzyl]‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₄F₃N₃O, (IV), there are no direction‐specific interactions between the molecules. In 3‐tert‐butyl‐7‐(4‐nitrobenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₂H₂₄N₄O₃, (V), a combination of C—H...O and C—H...N hydrogen bonds links the molecules into complex sheets. There are no direction‐specific interactions between the molecules of 3‐tert‐butyl‐7‐(2,3‐dimethoxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₄H₂₉N₃O₃, (VI), but a three‐dimensional framework is formed in 3‐tert‐butyl‐7‐(3,4‐methylenedioxybenzyl)‐1‐phenyl‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₃H₂₅N₃O₃, (VII), by a combination of C—H...O, C—H...N and C—H...π(arene) hydrogen bonds, while a combination of C—H...O and C—H...π(arene) hydrogen bonds links the molecules of 3‐tert‐butyl‐1‐phenyl‐7‐(3,4,5‐trimethoxybenzyl)‐6,7‐dihydro‐1H,4H‐pyrazolo[3,4‐d][1,3]oxazine, C₂₅H₃₁N₃O₄, (VIII), into complex sheets. In each compound, the oxazine ring adopts a half‐chair conformation, while the orientations of the pendent phenyl and tert‐butyl substituents relative to the pyrazolo[3,4‐d]oxazine unit are all very similar.     

Crystal structure,shape analysis and bioactivity of new LiI,NaI and MgII complexes with 1,10‐phenanthroline and 2‐(3,4‐dichlorophenyl)acetic acid

Reactions of 1,10‐phenanthroline (phen) and 2‐(3,4‐dichlorophenyl)acetic acid (dcaH) with M_n(CO₃) (M = Li^I, Na^I and Mg^II; n = 1 and 2) in MeOH yield the mononuclear lithium complex aqua[2‐(3,4‐dichlorophenyl)acetato‐κO](1,10‐phenanthroline‐κ²N,N′)lithium(I), [Li(C₈H₅Cl₂O₂)(C₁₂H₈N₂)(H₂O)] or [Li(dca)(phen)(H₂O)] ( 1 ), the dinuclear sodium complex di‐μ‐aqua‐bis{[2‐(3,4‐dichlorophenyl)acetato‐κO](1,10‐phenanthroline‐κ²N,N′)sodium(I)}, [Na₂(C₈H₅Cl₂O₂)₂(C₁₂H₈N₂)₂(H₂O)₂] or [Na₂(dca)₂(phen)₂(H₂O)₂] ( 2 ), and the one‐dimensional chain magnesium complex catena‐poly[[[diaqua(1,10‐phenanthroline‐κ²N,N′)magnesium]‐μ‐2‐(3,4‐dichlorophenyl)acetato‐κ²O:O′] 2‐(3,4‐dichlorophenyl)acetate monohydrate], {[Mg(C₈H₅Cl₂O₂)(C₁₂H₈N₂)(H₂O)₂](C₈H₅Cl₂O₂)·H₂O}_n or {[Mg(dca)(phen)(H₂O)₂](dca)·H₂O}_n ( 3 ). In these complexes, phen binds via an N,N′‐chelate pocket, while the deprotonated dca^? ligands coordinate either in a monodentate (in 1 and 2 ) or bidentate (in 3 ) fashion. The remaining coordination sites around the metal ions are occupied by water molecules in all three complexes. Complex 1 crystallizes in the triclinic space group P with one molecule in the asymmetric unit. The Li⁺ ion adopts a four‐coordinated distorted seesaw geometry comprising an [N₂O₂] donor set. Complex 2 crystallizes in the triclinic space group P with half a molecule in the asymmetric unit, in which the Na⁺ ion adopts a five‐coordinated distorted spherical square‐pyramidal geometry, with an [N₂O₃] donor set. Complex 3 crystallizes in the orthorhombic space group P2₁2₁2₁, with one Mg²⁺ ion, one phen ligand, two dca^? ligands and three water molecules in the asymmetric unit. Both dcaH ligands are deprotonated, however, one dca^? anion is not coordinated, whereas the second dca^? anion coordinates in a bidentate fashion bridging two Mg²⁺ ions, resulting in a one‐dimensional chain structure for 3 . The Mg²⁺ ion adopts a distorted octahedral geometry, with an [N₂O₄] donor set. Complexes 1 – 3 were evaluated against urease and α‐glucosidase enzymes for their inhibition potential and were found to be inactive.     

Two seven‐membered heterocycles with 1,2‐diaza ring N atoms: 3,5,7‐triphenyl‐1,2‐diazacyclohepta‐1(7),2‐diene and 3,7‐bis(2‐hydroxyphenyl)‐5‐phenyl‐1,2‐diazacyclohepta‐1(7),2‐diene

The title compounds, 3,5,7‐triphenyl‐1,2‐diazacyclohepta‐1(7),2‐diene, C₂₃H₂₀N₂, (I), and 3,7‐bis(2‐hydroxyphenyl)‐5‐phenyl‐1,2‐diazacyclohepta‐1(7),2‐diene, C₂₃H₂₀N₂O₂, (II), constitute the first structurally characterized examples of seven‐membered heterocycles with 1,2‐diaza ring N atoms. Compound (I) crystallizes in the space group P, with two independent molecules in the asymmetric unit that differ in the conformation of one of the phenyl rings, while (II) crystallizes in the space group C2/c. The C₅N₂ ring in each of (I) and (II) adopts a twist‐boat conformation. Compound (I) exhibits neither C—H...π interactions nor π–π stacking interactions, whereas (II) shows both intramolecular O—H...N hydrogen bonds and a C—H...π interaction that joins the molecules into an infinite chain in the [010] direction.     

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.     

Folded conformations due to arene interactions in dissymmetric and symmetric butylidene‐linker models based on pyrazolo[3,4‐d]pyrimidine,purine and 7‐deazapurine

The butylidene‐linker models 1‐[2‐(2,6‐dimethylsulfanyl‐9H‐purin‐9‐yl)‐2‐methylidenepropyl]‐4,6‐bis(methylsulfanyl)‐1H‐pyrazolo[3,4‐d]pyrimidine, C₁₈H₂₀N₈S₄, (XI), 7,7′‐(2‐methylidenepropane‐1,3‐diyl)bis[3‐methyl‐2‐methylsulfanyl‐3H‐pyrrolo[2,3‐d]pyrimidin‐4(7H)‐one], C₂₀H₂₂N₆O₂S₂, (XIV), and 7‐[2‐(4,6‐dimethylsulfanyl‐1H‐pyrazolo[3,4‐d]pyrimidin‐1‐yl)‐2‐methylidenepropyl]‐3‐methyl‐2‐methylsulfanyl‐3H‐pyrrolo[2,3‐d]pyrimidin‐4(7H)‐one, C₁₉H₂₁N₇OS₃, (XV), show folded conformations in solution, as shown by ¹H NMR analysis. This folding carries over to the crystalline state. Intramolecular π–π interactions are observed in all three compounds, but only (XIV) shows additional intramolecular C—H...π interactions in the solid state. As far as can be established, this is the first report incorporating the pyrrolo[2,3‐d]pyrimidine nucleus for such a study. In addition to the π–π interactions, the crystal structures are also stabilized by other weak intermolecular C—H...S/N/O and/or S...N/S interactions.     

Synthese und Kristallstrukturen von 1,1,3,3‐Tetramethylimidazolinium‐dichlorid und 1,1,4‐Trimethylpiperazinium‐chlorid

Synthesis and Crystal Structures of 1,1,3,3‐Tetramethylimidazolinium Dichloride and 1,1,4‐Trimethylpiperazinium Chloride Single crystals of 1,1,3,3‐tetramethylimidazolinium dichloride ( 1 ) and 1,1,4‐trimethylpiperazinium chloride ( 2 ) were obtained by reaction of CH₂Cl₂ with tetramethylethylenediamine (TMEDA) and NNN′N″N″‐pentamethyldiethylenetriamine (PMDETA), respectively. Both compounds are characterized by single crystal X‐ray diffraction and by IR spectroscopy. 1: [C₇H₁₈N₂]Cl₂, space group P2₁/c, Z = 4, lattice dimensions at 193(2) K: a = 821.97(11), b = 1130.38(8), c = 1143.08(13) pm, β = 100.348(15)°, R₁ = 0.0271. The C₇N₂ heterocyclic ring has envelope conformation like other salts with this dication. 2: [C₇H₁₇N₂]Cl, space group P2₁2₁2₁, Z = 4, lattice dimensions at 100(2) K: a = 1030.37(8), b = 1036.55(6), c = 831.39(4) pm, R₁ = 0.0180. Although the heterocyclic mono‐cation is without site symmetry in the crystal, its molecular symmetry is close to C_s, forming chair conformation of the C₄N₂ six‐membered ring.     

4‐(2‐Hydroxyphenyl)‐2‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepine and the 2‐(2,3‐dimethoxyphenyl)‐, 2‐(3,4‐dimethoxyphenyl)‐ and 2‐(2,5‐dimethoxyphenyl)‐substituted derivatives

The 1,5‐benzodiazepine ring system exhibits a puckered boat‐like conformation for all four title compounds [4‐(2‐hydroxyphenyl)‐2‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₁H₁₈N₂O, (I), 2‐(2,3‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (II), 2‐(3,4‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (III), and 2‐(2,5‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (IV)]. The stereochemical correlation of the two C₆ aromatic groups with respect to the benzodiazepine ring system is pseudo‐equatorial–equatorial for compounds (I) (the phenyl group), (II) (the 2,3‐dimethoxyphenyl group) and (III) (the 3,4‐dimethoxyphenyl group), while for (IV) (the 2,5‐dimethoxyphenyl group) the system is pseudo‐axial–equatorial. An intramolecular hydrogen bond between the hydroxyl OH group and a benzodiazepine N atom is present for all four compounds and defines a six‐membered ring, whose geometry is constant across the series. Although the molecular structures are similar, the supramolecular packing is different; compounds (I) and (IV) form chains, while (II) forms dimeric units and (III) displays a layered structure. The packing seems to depend on at least two factors: (i) the nature of the atoms defining the hydrogen bond and (ii) the number of intermolecular interactions of the types O—H...O, N—H...O, N—H...π(arene) or C—H...π(arene).     

Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity: structure–activity relationships

The search for new tuberculostatics is an important issue due to the increasing resistance of Mycobacterium tuberculosis to existing agents and the resulting spread of the pathogen. Heteroaryldithiocarbazic acid derivatives have shown potential tuberculostatic activity and investigations of the structural aspects of these compounds are thus of interest. Three new examples have been synthesized. The structure of methyl 2‐[amino(pyridin‐3‐yl)methylidene]hydrazinecarbodithioate, C₈H₁₀N₄S₂, at 293 K has monoclinic (P2₁/n) symmetry. It is of interest with respect to antibacterial properties. The structure displays N—H…N and N—H…S hydrogen bonding. The structure of N′‐(pyrrolidine‐1‐carbonothioyl)picolinohydrazonamide, C₁₁H₁₅N₅S, at 100 K has monoclinic (P2₁/n) symmetry and is also of interest with respect to antibacterial properties. The structure displays N—H…S hydrogen bonding. The structure of (Z)‐methyl 2‐[amino(pyridin‐2‐yl)methylidene]‐1‐methylhydrazinecarbodithioate, C₉H₁₃N₄S₂, has triclinic (P) symmetry. The structure displays N—H…S hydrogen bonding.     

Planarity of benzoylthiocarbazate tuberculostatics. IV. Polymorphs of N′‐(1,3‐dithiolan‐2‐ylidene)‐4‐nitrobenzohydrazide

The search for new tuberculostatics is important considering the occurrence of drug‐resistant strains of Mycobacterium tuberculosis . Three polymorphs of N ′‐(1,3‐dithiolan‐2‐ylidene)‐4‐nitrobenzohydrazide (a potentially tuberculostatic agent), C₁₀H₉N₃O₃S₂, denoted (I1), (I2) and (I3), and the monohydrate of this compound, C₁₀H₉N₃O₃S₂·H₂O, (I4), have been characterized by single‐crystal X‐ray diffraction. The conformations of the molecules in all these structures are very similar. Structures (I1), (I2) and (I3) provide an example of packing polymorphism resulting from different intermolecular interactions.     

Solvent‐mediated pseudo‐quadruple hydrogen‐bond motifs in three lamotrigine–carboxylic acid complexes

Lamotrigine, an antiepileptic drug, has been complexed with three aromatic carboxylic acids. All three compounds crystallize with the inclusion of N,N‐dimethylformamide (DMF) solvent, viz. lamotriginium [3,5‐diamino‐6‐(2,3‐dichlorophenyl)‐1,2,4‐triazin‐2‐ium] 4‐iodobenzoate N,N‐dimethylformamide monosolvate, C₉H₈Cl₂N₅⁺·C₇H₄IO₂⁻·C₃H₇NO, (I), lamotriginium 4‐methylbenzoate N,N‐dimethylformamide monosolvate, C₉H₇Cl₂N₅⁺·C₈H₈O₂⁻·C₃H₇NO, (II), and lamotriginium 3,5‐dinitro‐2‐hydroxybenzoate N,N‐dimethylformamide monosolvate, C₉H₈Cl₂N₅⁺·C₇H₃N₂O₇⁻·C₃H₇NO, (III). In all three structures, proton transfer takes place from the acid to the lamotrigine molecule. However, in (I) and (II), the acidic H atom is disordered over two sites and there is only partial transfer of the H atom from O to N. In (III), the corresponding H atom is ordered and complete proton transfer has occurred. Lamotrigine–lamotrigine, lamotrigine–acid and lamotrigine–solvent interactions are observed in all three structures and they thereby exhibit isostructurality. The DMF solvent extends the lamotrigine–lamotrigine dimers into a pseudo‐quadruple hydrogen‐bonding motif.     

Cocrystals of 6‐methyl‐2‐thiouracil: presence of the acceptor–donor–acceptor/donor–acceptor–donor synthon

The results of seven cocrystallization experiments of the antithyroid drug 6‐methyl‐2‐thiouracil (MTU), C₅H₆N₂OS, with 2,4‐diaminopyrimidine, 2,4,6‐triaminopyrimidine and 6‐amino‐3H‐isocytosine (viz. 2,6‐diamino‐3H‐pyrimidin‐4‐one) are reported. MTU features an ADA (A = acceptor and D = donor) hydrogen‐bonding site, while the three coformers show complementary DAD hydrogen‐bonding sites and therefore should be capable of forming an ADA/DAD N—H...O/N—H...N/N—H...S synthon with MTU. The experiments yielded one cocrystal and six cocrystal solvates, namely 6‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine–1‐methylpyrrolidin‐2‐one (1/1/2), C₅H₆N₂OS·C₄H₆N₄·2C₅H₉NO, (I), 6‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine (1/1), C₅H₆N₂OS·C₄H₆N₄, (II), 6‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine–N,N‐dimethylacetamide (2/1/2), 2C₅H₆N₂OS·C₄H₆N₄·2C₄H₉NO, (III), 6‐methyl‐2‐thiouracil–2,4‐diaminopyrimidine–N,N‐dimethylformamide (2/1/2), C₅H₆N₂OS·0.5C₄H₆N₄·C₃H₇NO, (IV), 2,4,6‐triaminopyrimidinium 6‐methyl‐2‐thiouracilate–6‐methyl‐2‐thiouracil–N,N‐dimethylformamide (1/1/2), C₄H₈N₅⁺·C₅H₅N₂OS⁻·C₅H₆N₂OS·2C₃H₇NO, (V), 6‐methyl‐2‐thiouracil–6‐amino‐3H‐isocytosine–N,N‐dimethylformamide (1/1/1), C₅H₆N₂OS·C₄H₆N₄O·C₃H₇NO, (VI), and 6‐methyl‐2‐thiouracil–6‐amino‐3H‐isocytosine–dimethyl sulfoxide (1/1/1), C₅H₆N₂OS·C₄H₆N₄O·C₂H₆OS, (VII). Whereas in cocrystal (I) an R₂²(8) interaction similar to the Watson–Crick adenine/uracil base pair is formed and a two‐dimensional hydrogen‐bonding network is observed, the cocrystals (II)–(VII) contain the triply hydrogen‐bonded ADA/DAD N—H...O/N—H...N/N—H...S synthon and show a one‐dimensional hydrogen‐bonding network. Although 2,4‐diaminopyrimidine possesses only one DAD hydrogen‐bonding site, it is, due to orientational disorder, triply connected to two MTU molecules in (III) and (IV).