Planarity of heteroaryldithiocarbazic acid derivatives showing tuberculostatic activity. IV. Diesters of benzoylcarbonohydrazonodithioic acid

Dimethyl (3,4‐dichlorobenzoyl)carbonohydrazonodithioate, C₁₀H₁₀Cl₂N₂OS₂, (D1), dibenzyl (3,4‐dichlorobenzoyl)carbonohydrazonodithioate, C₂₂H₁₈Cl₂N₂OS₂, (D2), dimethyl (3,4‐dichlorobenzoyl)‐1‐methylcarbonohydrazonodithioate, C₁₁H₁₂Cl₂N₂OS₂, (D3), 3,4‐dichloro‐N′‐(1,3‐dithiolan‐2‐ylidene)‐N‐methylbenzohydrazide, C₁₁H₁₀Cl₂N₂OS₂, (D4), were synthesized as potential tuberculostatics. Compound (D1) (with two molecules in the asymmetric unit) was the only one showing tuberculostatic activity of the same range as the common drugs isoniazid and pyrazinamide. The molecular structures of the studied compounds depend on the substitution at the N atom adjacent to the carbonyl group. In the case of the unsubstituted derivatives (D1) and (D2), their central frames are generally planar with a twist of the 3,4‐dichlorophenyl ring by 30–40°. Until now, coplanarity of the aromatic ring with the (methylene)carbonohydrazone fragment has been considered a prerequisite for tuberculostatic activity. The N‐methylated derivatives (D3) and (D4) show an additional twist along the N—C(=O) bond by 20–30° due to the spatial repulsion introduced by the methyl substituent.     

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.     

(Z)‐5‐[(5‐Methyl‐1H‐imidazol‐4‐yl)methylidene]‐2‐sulfanylidene‐1,3‐thiazolidin‐4‐one monohydrate: a three‐dimensional hydrogen‐bonded framework structure

The non‐H atoms in the organic component of the title compound, C₈H₇N₃OS₂·H₂O, are almost coplanar, as the dihedral angle between the two ring planes is only 1.8 (2)°; there is a wide C—C—C angle of 127.8 (3)° at the methine C atom linking the two rings. The molecular components are linked into a three‐dimensional framework structure by two‐centre hydrogen bonds of N—H...O and O—H...N types, together with a three‐centre O—H...(N,S) system. Comparisons are made with some (Z)‐5‐arylmethylidene‐2‐sulfanylidene‐1,3‐thiazolidin‐4‐ones.     

6‐(2‐Hydro­xy­benzoyl)‐5‐(pyrrol‐2‐yl)‐3H‐pyrrolizine

The title compound, 2‐hydroxy­phenyl 5‐(pyrrol‐2‐yl)‐3H‐pyrrolizin‐6‐yl ketone, C₁₈H₁₄N₂O₂, was isolated from the base‐catalyzed 1:2 condensation of 2‐hydroxy­aceto­phenone with pyrrole‐2‐carbaldehyde. The pyrrole N—H and hydroxy­benzoyl O—H groups are hydrogen bonded to the benzoyl O atom. The allyl­ic C=C double bond of the 3H‐pyrrolizine system is located between ring positions 1 and 2, the C atom at position 3 (adjacent to the N atom) being single bonded.     

1‐Benzoyl‐3‐[(2‐benzylsulfanyl)phenyl]thiourea

In the title compound, C₂₁H₁₈N₂OS₂, a strong intramolecular N—H...O hydrogen bond [N...O = 2.642 (3) Å] between the amide N atom and the benzoyl O atom forms an almost planar six‐membered ring in the central part of the molecule. In the crystal, molecules are packed through weak N—H...S interactions. Intra‐ and intermolecular hydrogen bonds and van der Waals interactions are the stabilizing forces for the crystal structure.     

Hydrogen‐bonded ribbons in ethyl (E)‐3‐[2‐amino‐4,6‐bis(dimethylamino)pyrimidin‐5‐yl]‐2‐cyanoacrylate and 2‐[(2‐amino‐4,6‐di‐1‐piperidylpyrimidin‐5‐yl)methylene]malononitrile

The pyrimidine rings in ethyl (E)‐3‐[2‐amino‐4,6‐bis(dimethylamino)pyrimidin‐5‐yl]‐2‐cyanoacrylate, C₁₄H₂₀N₆O₂, (I), and 2‐[(2‐amino‐4,6‐di‐1‐piperidylpyrimidin‐5‐yl)methylene]malononitrile, C₁₈H₂₃N₇, (II), which crystallizes with Z′ = 2 in the space group, are both nonplanar with boat conformations. The molecules of (I) are linked by a combination of N—H...N and N—H...O hydrogen bonds into chains of edge‐fused R₂²(8) and R₄⁴(20) rings, while the two independent molecules in (II) are linked by four N—H...N hydrogen bonds into chains of edge‐fused R₂²(8) and R₂²(20) rings. This study illustrates both the readiness with which highly‐substituted pyrimidine rings can be distorted from planarity and the significant differences between the supramolecular aggregation in two rather similar compounds.     

Methyl 2‐benzamido‐4‐(3,4‐dimethoxyphenyl)‐5‐methylbenzoate and N‐{5‐benzoyl‐2‐[(Z)‐2‐methoxyethenyl]‐4‐methylphenyl}benzamide

Methyl 2‐benzamido‐4‐(3,4‐dimethoxyphenyl)‐5‐methylbenzoate, C₂₄H₂₃NO₅, (Ia), and N‐{5‐benzoyl‐2‐[(Z)‐2‐methoxyethenyl]‐4‐methylphenyl}benzamide, C₂₄H₂₁NO₃, (IIa), were formed via a Diels–Alder reaction of appropriately substituted 2H‐pyran‐2‐ones and methyl propiolate or (Z)‐1‐methoxybut‐1‐en‐3‐yne, respectively. Each of these cycloadditions might yield two different regioisomers, but just one was obtained in each case. In (Ia), an intramolecular N—H...O hydrogen bond closes a six‐membered ring. A chain is formed due to aromatic π–π interactions, and a three‐dimensional framework structure is formed by a combination of C—H...O and C—H...π(arene) hydrogen bonds. Compound (IIa) was formed not only regioselectively but also chemoselectively, with just the triple bond reacting and the double bond remaining unchanged. Compound (IIa) crystallizes as N—H...O hydrogen‐bonded dimers stabilized by aromatic π–π interactions. Dimers of (IIa) are connected into a chain by weak C—H...π(arene) interactions.     

(8RS)‐4‐Amino‐6‐(4‐chlorophenyl)‐8‐(2,4‐dichlorothiazol‐5‐yl)‐8,9‐dihydro‐7H‐pyrimido[4,5‐b][1,4]diazepine N,N‐dimethylformamide monosolvate: sheets built from N—H...N and C—H...O hydrogen bonds

In the title compound, C₁₆H₁₁Cl₃N₆S·C₃H₇NO, the seven‐membered ring adopts a conformation which is close to the twist‐boat form. The molecular components are linked into sheets by a combination of two N—H...N hydrogen bonds and two C—H...O hydrogen bonds. Comparisons are made with other aminopyrimidine derivatives.     

Two methyl 3‐(1H‐pyrazol‐4‐yl)octahydropyrrolo[3,4‐c]pyrrole‐1‐carboxylates form different hydrogen‐bonded sheets

In the molecules of both methyl (1RS,3SR,3aRS,6aSR)‐1‐methyl‐3‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐4,6‐dioxo‐5‐phenyloctahydropyrrolo[3,4‐c]pyrrole‐1‐carboxylate, C₂₅H₂₄N₄O₄, (I), and methyl (1RS,3SR,3aRS,6aSR)‐5‐(4‐chlorophenyl)‐1‐methyl‐3‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐4,6‐dioxooctahydropyrrolo[3,4‐c]pyrrole‐1‐carboxylate, C₂₅H₂₃ClN₄O₄, (II), the two rings of the pyrrolopyrrole fragment are both nonplanar, with conformations close to half‐chair forms. The overall conformations of the molecules of (I) and (II) are very similar, apart from the orientation of the ester function. The molecules of (I) are linked into sheets by a combination of an N—H...π(pyrrole) hydrogen bond and three independent C—H...O hydrogen bonds. The molecules of (II) are also linked into sheets, which are generated by a combination of an N—H...N hydrogen bond and two independent C—H...O hydrogen bonds, weakly augmented by a C—H...π(arene) hydrogen bond.     

Hydrogen‐bonded chains of rings in 1‐(4‐chloroanilinomethyl)‐5‐(4‐chlorophenyl)‐1,3,5‐triazinane‐2‐thione and hydrogen‐bonded sheets in 1‐anilinomethyl‐5‐phenyl‐1,3,5‐triazinane‐2‐thione

In 1‐(4‐chloroanilinomethyl)‐5‐(4‐chlorophenyl)‐1,3,5‐triazinane‐2‐thione, C₁₆H₁₆Cl₂N₄S, there are two independent molecules in the asymmetric unit which form inversion dimers via two weak N—H...S hydrogen bonds. The dimers are then linked into C(9)C(14) chains by a C—H...S hydrogen bond and a C—H...Cl contact. In 1‐(anilinomethyl)‐5‐phenyl‐1,3,5‐triazinane‐2‐thione, C₁₆H₁₈N₄S, molecules are linked into complex sheets via a combination of N—H...S and C—H...π hydrogen bonds.     

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.     

2,3,12,13‐Tetrabromo‐5,10,15,20‐tetrakis(4‐butoxyphenyl)porphyrin 1,2‐dichloroethane solvate

Nonmesogenic 2,3,12,13‐tetrabromo‐5,10,15,20‐tetrakis(4‐butoxyphenyl)porphyrin crystallizes as the title 1,2‐dichloroethane solvate, C₆₀H₅₈Br₄N₄O₄·C₂H₄Cl₂. The porphyrin ring shows a nonplanar conformation, with an average mean plane displacement of the β‐pyrrole C atoms from the 24‐atom (C₂₀N₄) core of ±0.50 (3) Å. The 1,2‐dichloroethane solvent is incorporated between the porphyrin units and induces the formation of one‐dimensional chains via interhalogen Cl...Br and butyl–aryl C—H...π interactions. These chains are oriented along the unit‐cell a axis, with the macrocyclic ring planes lying almost parallel to the (010) plane. The chains are arranged in an offset fashion by aligning the butoxy chains approximately above or below the faces of the adjacent porphyrin core, resulting in decreased interporphyrin π–π interactions, and they are held together by weak intermolecular (C—Br...π, C—H...π and C—H...Br) interactions. The nonplanar geometry of the macrocyclic ring is probably due to the weak interporphyrin interactions induced by the solvent molecule and the peripheral butoxy groups. The nonplanarity of the mesogens could influence the mesogenic behaviour differently relative to planar porphyrin mesogens.     

Hydrogen‐bonded chains in 2,2,2‐trichloro‐N,N′‐bis(4‐methoxyphenyl)ethane‐1,1‐diamine and a three‐dimensional hydrogen‐bonded framework in 2,2,2‐trichloro‐N,N′‐bis(4‐chlorophenyl)ethane‐1,1‐diamine

In 2,2,2‐trichloro‐N,N′‐bis(4‐methoxyphenyl)ethane‐1,1‐diamine, C₁₆H₁₇Cl₃N₂O₂, molecules are linked into helical chains by N—H...O hydrogen bonds. Molecules of 2,2,2‐trichloro‐N,N′‐bis(4‐chlorophenyl)ethane‐1,1‐diamine, C₁₄H₁₁Cl₅N₂, are connected into a three‐dimensional framework by two independent Cl...Cl interactions and one C—H...Cl hydrogen bond.     

7‐Vinyl‐8‐aza‐7‐de­aza‐2′‐deoxy­adenosine monohydrate

In the title compound, 4‐amino‐1‐(2‐deoxy‐β‐d ‐eythro‐pento­furan­osyl)‐3‐vinyl‐1H‐pyrazolo­[3,4‐d]­pyrimidine monohydrate, C₁₂H₁₅N₅O₃·H₂O, the conformation of the gly­cosyl bond is anti. The furan­ose moiety is in an S conformation with an unsymmetrical twist, and the conformation at the exocyclic C—C(OH) bond is +sc (gauche, gauche). The vinyl side chain is bent out of the heterocyclic ring plane by 147.5 (5)°. The three‐dimensional packing is stabilized by O—H·O, O—H·N and N—H·O hydrogen bonds.     

Supramolecular aggregation in three 4‐aryl‐6‐(1H‐indol‐3‐yl)‐3‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitriles

Both 6‐(1H‐indol‐3‐yl)‐3‐methyl‐4‐(4‐methylphenyl)‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile and 6‐(1H‐indol‐3‐yl)‐3‐methyl‐4‐(4‐methoxyphenyl)‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile crystallize from dimethylformamide solutions as stoichiometric 1:1 solvates, viz. C₂₉H₂₁N₅·C₃H₇NO, (I), and C₂₉H₂₁N₅O·C₃H₇NO, (II), respectively; however, 6‐(1H‐indol‐3‐yl)‐3‐methyl‐1‐phenyl‐4‐(3,4,5‐trimethoxyphenyl)‐1H‐pyrazolo[3,4‐b]pyridine‐5‐carbonitrile, C₃₁H₂₅N₅O₃, (III), crystallizes in the unsolvated form. The heterocyclic components of (I) are linked by C—H...π(arene) hydrogen bonds to form cyclic centrosymmetric dimers, from which the solvent molecules are pendent, linked by N—H...O hydrogen bonds. In (II), the heterocyclic components are linked by a combination of C—H...N and C—H...π(arene) hydrogen bonds into chains containing two types of centrosymmetric ring, and the pendent solvent molecules are linked to these chains by N—H...O hydrogen bonds. Molecules of (III) are linked into simple C(12) chains by an N—H...O hydrogen bond, and these chains are weakly linked into pairs by an aromatic π–π stacking interaction.     

Two N,N′‐diaryl‐2,2,2‐trichloroethane‐1,1‐diamines: hydrogen‐bonded supramolecular structures in one and two dimensions

The molecules of 2,2,2‐trichloro‐N,N′‐diphenylethane‐1,1‐diamine, C₁₄H₁₃Cl₃N₂, are linked into (040) sheets by a combination of C—H...Cl and C—H...π(arene) hydrogen bonds. In 2,2,2‐trichloro‐N,N′‐bis(4‐methylphenyl)ethane‐1,1‐diamine, C₁₆H₁₇Cl₃N₂, the molecules are linked into C(7) chains by two independent C—H...Cl hydrogen bonds and one Cl...Cl contact.     

3,4‐Di‐2‐pyridyl‐1,2,5‐oxadiazole and its perchlorate salt

In 3,4‐di‐2‐pyridyl‐1,2,5‐oxadiazole (dpo), C₁₂H₈N₄O, each mol­ecule resides on a twofold axis and inter­acts with eight neighbours via four C—H⋯N and four C—H⋯O inter­actions to generate a three‐dimensional hydrogen‐bonded architecture. In the perchlorate analogue, 2‐[3‐(2‐pyrid­yl)‐1,2,5‐oxadiazol‐4‐yl]pyridinium perchlorate, C₁₂H₉N₄O⁺·ClO₄⁻ or [Hdpo]ClO₄, the [Hdpo]⁺ cation is bisected by a crystallographic mirror plane, and the additional H atom in the cation is shared by the two pyridyl N atoms to form a symmetrical intra­molecular N⋯H⋯N hydrogen bond. The cations and perchlorate anions are linked through C—H⋯O hydrogen bonds and π–π stacking inter­actions to form one‐dimensional tubes along the b‐axis direction.     

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.     

A three‐dimensional hydrogen‐bonded framework in 2‐amino‐6‐(N‐methylanilino)pyrimidin‐4(3H)‐one and a ribbon of fused hydrogen‐bonded rings in 2‐amino‐6‐(N‐methylanilino)‐5‐nitropyrimidin‐4(3H)‐one

The molecular dimensions of both 2‐amino‐6‐(N‐methylanilino)pyrimidin‐4(3H)‐one, C₁₁H₁₂N₄O, (I), and 2‐amino‐6‐(N‐methylanilino)‐5‐nitropyrimidin‐4(3H)‐one, C₁₁H₁₁N₅O₃, (II), are consistent with considerable polarization of the molecular–electronic structures. The molecules of (I) are linked into a three‐dimensional framework by a combination of one N—H...N hydrogen bond, two independent N—H...O hydrogen bonds and one C—H...π(arene) hydrogen bond. The molecules of (II) are linked into ribbons containing three types of edge‐fused ring by the combination of two independent three‐centre N—H...(O)₂ hydrogen bonds.     

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).