Two carbamoyl‐substituted di­hydro­pyrimidines: potential mimics of di­hydro­pyridine calcium channel blockers

The structures of two conformationally similar 1,4‐di­hydro­pyrimidines with a novel carbamoyl substitution, viz. 6‐methyl‐5‐(N‐methyl­carbamoyl)‐4‐phenyl‐1,2,3,4‐tetrahydro­py­rimidine‐2‐thione monohydrate, C₁₃H₁₅N₃OS·H₂O, (I), and 4‐(4‐chloro­phenyl)‐6‐methyl‐5‐(N‐methyl­carbamoyl)‐1,2,3,4‐tetra­hydro­pyrimidine‐2‐thione monohydrate, C₁₃H₁₄ClN₃OS·H₂O, (II), exhibit the structural features of 1,4‐di­hydro­pyridine calcium channel blockers. In both structures, the pyrimidine ring adopts a flattened boat conformation and the carbamoyl side chain is in an extended conformation with an anticlinal orientation. The phenyl ring occupies a pseudo‐axial position with respect to the pyrimidine ring in these structures. Both compounds crystallize with one mol­ecule of water, which participates in a two‐dimensional hydrogen‐bonding network. The mol­ecules are linked into dimers by N—H·S hydrogen bonds in both structures.     

Bis­[1‐(p‐chloro­phenyl)‐5‐iso­propyl­biguanide‐κ2N2,N4]­nickel(II) dichloride di­methyl­form­amide solvate

The asymmetric unit of the title compound, [Ni(C₁₁H₁₆ClN₅)₂]Cl₂·C₃H₇NO, contains one monomeric nickel(II) com­plex cation, two Cl⁻ anions and one di­methyl­form­amide sol­vent mol­ecule. The Ni atom is coordinated to each of two 1‐­(p‐chloro­phenyl)‐5‐iso­propyl­biguanide (proguanil) ligands via two N atoms. The complex exhibits a square‐planar coordination, with the Ni atom lying 0.021 (2) Å out of the basal plane. The crystal packing is characterized by several hydrogen bonds.     

Supramolecular hydrogen‐bonded hexamers in two 5‐aryl‐3‐methyl‐1‐phenyl‐1,6,7,8‐tetra­hydro­pyrazolo­[3,4‐b][1,4]­diazepines

In both title compounds, i.e. 3‐methyl‐1,5‐di­phenyl‐1,6,7,8‐tetra­hydro­pyrazolo­[3,4‐b][1,4]­diazepine, C₁₉H₁₈N₄, (I), and 5‐(4‐chloro­phenyl)‐3‐methyl‐1‐phenyl‐1,6,7,8‐tetra­hydro­pyra­zolo­[3,4‐b][1,4]­diazepine, C₁₉H₁₇ClN₄, (II), an N—H?N hydrogen bond links six mol­ecules to form an R(30) ring. Compound (I) crystallizes in the R space group and (II) crystallizes in P with three mol­ecules in the asymmetric unit. The mol­ecule of (I) contains a disordered seven‐membered ring.     

(o‐Benzo­quinone di­imine‐N,N′)dichlorobis(tri­phenyl­phosphine‐P)ruthenium(II) 1.33‐methanol 0.33‐di­chloro­methane solvate

The Ru atom in the title compound, [RuCl₂{P(C₆H₅)₃}₂{C₆H₄(NH)₂}]·1.33CH₃OH·0.33CH₂Cl₂, shows a six‐coordinate octahedral geometry, with a trans arrangement of the tri­phenyl­phosphine groups. One and a half mol­ecules of complex, two mol­ecules of methanol and a half mol­ecule of di­chloro­methane form the asymmetric unit, with crystallographic twofold rotation symmetry for the complex mol­ecule in a special position.     

Alaninyl­tryptophan hydrate,glycyl­tryptophan dihydrate and tryptophyl­glycine hydrate

The crystal structures of the title tryptophan‐containing dipeptides, C₁₄H₁₇N₃O₃·H₂O, (I), C₁₃H₁₅N₃O₃·2H₂O, (II), and C₁₃H₁₅N₃O₃·H₂O, (III), respectively, contain at least one water mol­ecule of solvation. As a result, the crystal packing of these compounds is composed of regions of water‐mediated hydrogen bonding and tryptophan ring‐to‐ring stacking separated by the length of the mol­ecule. The tryptophan rings stack in a continuous layer that, when viewed edge‐on from the outermost part of the tryptophan ring, exhibits a herring‐bone motif. However, owing to the lack of direct overlap of adjacent rings, no degree of π contact or long‐range delocalization of ring systems is possible here. The overall molecular conformations of (I) and (III) contain a folding of one peptide over the other, such that a minimum in molecular volume occurs without any intramolecular hydrogen bonding. In these two dipeptides, extensive hydrogen bonding is observed to and from the single water mol­ecule of solvation. In the crystal structure of (II), however, an extended mol­ecule conformation complements a more extensive hydrogen‐bonding scheme involving two water mol­ecules of solvation per dipeptide.     

Two hydrates of 2,6‐bis­(1H‐benzimidazol‐2‐yl)­pyridine

The structures of the mono‐ and sesquihydrates of 2,6‐bis(1H‐benz­imi­da­zol‐2‐yl)­pyridine (bbip) are reported. Phase (I), C₁₉H₁₃N₅·H₂O, has one water and one bbip mol­ecule in the asymmetric unit, while phase (II), C₁₉H₁₃N₅·1.5H₂O, has three water mol­ecules and two bbip mol­ecules in the asymmetric unit. The compounds exhibit very similar molecular geom­etries but different packing organizations, which result from intricate hydrogen‐bonding schemes.     

Two polymorphs,with Z′ = 1 and 2, of 2‐amino‐4‐chloro‐6‐morpholino­pyrimidine in P21/c,and 2‐amino‐4‐chloro‐6‐piperidino­pyrimidine,which is isomorphous and almost isostructural with the Z′ = 2 polymorph

Crystallization of 2‐amino‐4‐chloro‐6‐morpholino­pyrimidine, C₈H₁₁ClN₄O, (I), yields two polymorphs, both with space group P2₁/c, having Z′ = 1 (from diethyl ether solution) and Z′ = 2 (from di­chloro­methane solution), denoted (Ia) and (Ib), respectively. In polymorph (Ia), the mol­ecules are linked by an N—H⋯O and an N—H⋯N hydrogen bond into sheets built from alternating R(8) and R(40) rings. In polymorph (Ib), one mol­ecule acts as a triple acceptor of hydrogen bonds and the other acts as a single acceptor; one N—H⋯O and three N—H⋯N hydrogen bonds link the mol­ecules in a complex chain containing two types of R(8) and one type of R(18) ring. 2‐Amino‐4‐chloro‐6‐piperidino­pyrimidine, C₉H₁₃ClN₄, (II), which is isomorphous with polymorph (Ib), also has Z′ = 2 in P2₁/c, and the mol­ecules are linked by three N—­H⋯N hydrogen bonds into a centrosymmetric four‐mol­ecule aggregate containing three R(8) rings.     

4‐Acetamido‐3,3,5,5‐[2H4]‐2,2,6,6‐tetra­([2H3]methyl)piperidin‐1‐yloxyl 0.33‐hydrate

The asymmetric unit of the title compound, C₁₁H₅D₁₆N₂O₂·0.33H₂O, is formed by three crystallographically independent piperidin‐1‐yloxyl mol­ecules and a mol­ecule of water. The mol­ecules are crosslinked by nine hydrogen bonds into layers parallel with the ac plane. The water mol­ecule contributes to the stability of the low‐symmetry arrangement by four hydrogen bonds.     

The first salt of an isolated penta­chloro­plumbate(II) trianion

The title compound, tris(cyclo­hexane‐1,2‐diamine‐κ²N,N′)cobalt penta­chloro­plum­bate sesquihydrate, [Co(C₆H₁₄N₂)₃][PbCl₅]·1.5H₂O, crystallizes in the monoclinic space group C2/c, with a tricationic cobalt complex, a penta­chloro­plumbate trianion, one water mol­ecule in a general position and a second water mol­ecule on a crystallographic twofold axis. The compound is the first example of an isolated [PbCl₅]³⁻ moiety; the Pb atom is coordinated in a square‐pyramidal fashion, with four longer bonds to Cl atoms in the basal plane and a shorter distance to the apex. The ionic constituents and the solvent mol­ecules form a three‐dimensional network of hydrogen bonds.     

[2,6‐Bis(1H‐benzimidazol‐2‐yl‐κN3)­pyridine‐κN](di­methyl­form­amide‐κO)­(thio­sulfato‐κ2O,S)­nickel(II) mono­hydrate

The structure of the title compound, [Ni(ths)(bbip)(dmf)]·­H₂O [ths is thio­sulfate, S₂O₃; bbip is 2,6‐bis(1H‐benz­imidazol‐2‐yl)­pyridine, C₂₁H₁₃N₅; and dmf is di­methyl­form­amide, C₃H₇NO], is monomeric, with the nickel ion octahe­drally surrounded by an N,N′,N′′‐tridentate bbip mol­ecule, an S,O‐bidentate ths mol­ecule and an O‐monodentate dmf mol­ecule. The H atoms of the hydration water mol­ecule and the amino groups of bbip are involved in hydrogen bonding and determine a spatial organization of broad layers parallel to (001), which are connected by weak interactions.     

Packing effects in 4,4′‐bis(4‐hydroxy­butyl)‐2,2′‐bi­pyridine and 4,4′‐bis(4‐bromo­butyl)‐2,2′‐bi­pyridine

Structure analyses of 4,4′‐bis(4‐hydroxy­butyl)‐2,2′‐bi­pyridine, C₁₈H₂₄N₂O₂, (I), and 4,4′‐bis(4‐bromo­butyl)‐2,2′‐bi­pyridine, C₁₈H₂₂Br₂N₂, (II), reveal intermolecular hydrogen bonding in both compounds. For (I), O—H·N intermolecular hydrogen bonding leads to the formation of an infinite two‐dimensional polymer, and π stacking interactions are also observed. For (II), C—H·N intermolecular hydrogen bonding leads to the formation of a zigzag polymer. The two compounds crystallize in different crystal systems, but both mol­ecules possess C_i symmetry, with one half mol­ecule in the asymmetric unit.     

Hexa­methyl­enetetra­mine–4‐nitro­catechol–water (1/2/1)

In the title adduct, 1,3,5,7‐tetra­aza­tri­cyclo[3.3.1.1^3,7]dec­ane–4‐nitro­benzene‐1,2‐diol–water (1/2/1), C₆H₁₂N₄·2C₆H₅NO₄·H₂O, the hexa­methyl­ene­tetra­mine mol­ecule acts as an acceptor of intermolecular O—H?N hydrogen‐bonding interactions from the water mol­ecule and the hydroxy groups of one of the two symmetry‐independent 4‐nitro­catechol mol­ecules. The structure is built from molecular layers which are stabilized by three intermolecular O—H?O, two intermolecular O—H?N and four intermolecular C—H?O hydrogen bonds. The layers are further interconnected by one additional intermolecular O—H?N and two intermolecular C—H?O hydrogen bonds.     

9‐(Tri­chloro­acetyl­imino)­acridine monohydrate

The title compound, alternatively called N‐acridin‐9(10H)‐yl­idene‐2,2,2‐tri­chloro­acet­amide mono­hydrate, C₁₅H₉Cl₃N₂O·H₂O, crystallizes in space group P2₁/c with Z = 4. The acridine moieties are arranged in layers, tilted at an angle of 15.20 (4)° relative to the ac plane, while adjacent mol­ecules pack in a head‐to‐tail manner. Acridine and water mol­ecules form columns along the b axis held in place by a network of hydrogen bonds, which is the major factor stabilizing the lattice. The acridine mol­ecule exhibits structural features of both the amino and imino forms, which could be due to the presence of the strong electronegative tri­chloro­acetyl substituent at the exocyclic N atom.     

Methyl 1‐(4‐chloro­benzyl)‐2‐(4‐methyl­piperazin‐1‐yl)‐1H‐benz­imidazole‐5‐carboxyl­ate hemihydrate

The title compound, C₂₁H₂₃ClN₄O₂·0.5H₂O, contains two independent mol­ecules in the asymmetric unit. In each mol­ecule the piperazine ring adopts a chair conformation; the deviations of the piperazine N atoms from the best plane through the remaining four C atoms are ?0.678 (3) and 0.662 (3) Å in mol­ecule A, and 0.687 (3) and ?0.700 (3) Å in mol­ecule B. The mol­ecules are linked by two hydrogen bonds of the O—H?N type involving the O atom of the water mol­ecule of crystallization.     

Solvates of zafirlukast

The crystal structures of three solvates of zafirlukast [systematic name: cyclopentyl N‐{1‐methyl‐3‐[2‐methyl‐4‐(o‐tolylsulfonylaminocarbonyl)benzyl]‐1H‐indol‐5‐yl}carbamate], viz. the monohydrate, C₃₁H₃₃N₃O₆S·H₂O, (I), the methanol solvate, C₃₁H₃₃N₃O₆S·CH₃OH, (II), and the ethanol solvate, C₃₁H₃₃N₃O₆S·C₂H₅OH, (III), have been determined by single‐crystal X‐ray diffraction analysis. All three compounds crystallize in the monoclinic crystal system. Zafirlukast adopts a similar Z‐shaped conformation in all three solvates. The methanol and ethanol solvates are isostructural. The packing of the zafirlukast mol­ecules in all three crystal structures is similar and is expressed by hydrogen‐bonded mol­ecules that are related by translation, along (101) in (I) and along the b axis in (II) and (III). The methanol and ethanol solvent mol­ecules are hydrogen bonded to two mol­ecules of zafirlukast. The water mol­ecule, on the other hand, acts as a connector via hydrogen bonds between three mol­ecules of zafirlukast. The solvent mol­ecules are not released at temperatures below the melting points of the solvates.     

Tris(1H‐benzimidazol‐2‐yl­meth­yl)­amine–solvent adducts

The tris­(1H‐benzimidazol‐2‐yl­meth­yl)­amine (ntb) mol­ecule crystallizes in different solvent systems, resulting in two kinds of adduct, namely the monohydrate, C₂₄H₂₁N₇·H₂O or ntb·H₂O, (I), and the acetonitrile–methanol–water (1/0.5/1.5) solvate, C₂₄H₂₁N₇·C₂H₃N·0.5CH₄O·1.5H₂O or ntb·1.5H₂O·0.5MeOH·MeCN, (II). In both cases, ntb adopts a tripodal mode to form hydrogen bonds with a solvent water mol­ecule via two N—H⋯O and one O—H⋯N hydrogen bond. In (I), the ntb·H₂O adduct is further assembled into a two‐dimensional network by N—H⋯N and O—H⋯N hydrogen bonds, while in (II), a double‐stranded one‐dimensional chain structure is assembled via N—H⋯O and O—H⋯O hydrogen bonds, with the acetonitrile mol­ecules located inside the cavities of the chain structure.     

Clemizoledichlorocobalt(II)

The structure of di­chloro­[1‐(p‐chloro­benzyl)‐2‐(1‐pyrrol­idinyl­methyl‐N)‐1,3‐benz­imidazole‐N³]­cobalt(II), [Co­Cl₂(C₁₉­H₂₀ClN₃)], contains a mol­ecule of clemizole bound in a bidentate manner to cobalt through its imidazole and pyrrolidinyl N atoms, with significantly different Co—N distances of 1.976 (5) and 2.126 (5) Å, respectively. The geometry around cobalt is distorted tetrahedral, with significantly different Co—Cl distances of 2.217 (2) and 2.233 (2) Å, and the pyrrolidinyl ring is disordered.     

3‐(1‐Pyridinio)propane­sulfonate and 3‐(benzyl­dimethyl­ammonio)propane­sulfonate monohydrate

3‐(1‐Pyridinio)propane­sulfonate, C₈H₁₁NO₃S, and 3‐(benzyl­dimethyl­ammonio)propane­sulfonate monohydrate, C₁₂H₁₉NO₃S·H₂O, used as additives during protein refolding and crystallization, both crystallize in the monoclinic system in the P2₁/c space group, with one mol­ecule (or one set of mol­ecules) per asymmetric unit. The solvent water mol­ecule present in the second crystal structure results in the formation of a dimer through hydrogen bonds. The conformation of the propane­sulfonate moiety is similar in both structures.     

3,5‐Di­amino‐6‐(2‐fluoro­phenyl)‐1,2,4‐triazine–di­methyl­form­amide (1/1)

The title compound, C₉H₈FN₅·C₃H₇NO, contains two independent complexes in the asymmetric unit, each consisting of one 3,5‐di­amino‐6‐(2‐fluoro­phenyl)‐1,2,4‐triazine mol­ecule and one di­methyl­form­amide solvent mol­ecule. One triazine mol­ecule is disordered over two conformations within the crystal, the occupancies being 62 (1) and 38 (1)%. The phenyl ring of this mol­ecule resolves into two conformations rotated by almost 180° about the bridging bond between the two rings, while the triazine rings approximately superimpose on each other. The triazine mol­ecules of the asymmetric unit differ in the dihedral angles between their respective phenyl and triazine ring planes, these being 57.6 (2)° for the fully occupied, and 76.9 (6) and 106.8 (8)° for the partially occupied mol­ecules. An extensive network of hydrogen bonds maintains the crystal structure.     

(E)‐8‐(3‐Chloro­styr­yl)‐1,3,7‐trimethylxanthine,a caffeine derivative acting both as antagonist of adenosine A2A receptors and as inhibitor of MAO‐B

In the crystal structure of (E)‐8‐(3‐chloro­styr­yl)‐1,3,7‐trimethylxanthine (CSC) [systematic name: (E)‐8‐(3‐chloro­styr­yl)‐1,3,7‐trimethyl‐3,7‐dihydro‐1H‐purine‐2,6‐dione], C₁₆H₁₅ClN₄O₂, the xanthine ring and the lateral styryl chain are coplanar. The crystal packing involves mainly parallel stacking of these planar mol­ecules. The electrostatic potential calculated on the crystal structure conformation confirms the pharmacophore elements associated with MAO‐B inhibition.