Covalent-assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4-tert-butylbenzoic acid with isoniazid and its derivatized forms.

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4-tert-butylbenzoic acid via a one-pot covalent and supramolecular synthesis, namely 4-tert-butylbenzoic acid-isoniazid, C6H7N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(propan-2-ylidene)isonicotinohydrazide, C9H11N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(butan-2-ylidene)isonicotinohydrazide, C10H13N3O·C11H14O2, 4-tert-butylbenzoic acid-N'-(diphenylmethylidene)isonicotinohydrazide, C19H15N3O·C11H14O2, and 4-tert-butylbenzoic acid-N'-(4-hydroxy-4-methylpentan-2-ylidene)isonicotinohydrazide, C12H17N3O2·C11H14O2. The co-former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan-2-one, butan-2-one, benzophenone and 3-hydroxy-3-methylbutan-2-one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of its derivatives. The remaining hydrogen-bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems.

Energetic propane-1,3-diaminium and butane-1,4-diaminium salts of N,N'-dinitroethylenediazanide: syntheses, crystal structures and thermal properties.

The acidity of the amine H atoms and the consequent salt formation ability of ethylenedinitramine (EDNA) were analyzed in an attempt to improve the thermal stability of EDNA. Two short-chain alkanediamine bases, namely propane-1,3-diamine and butane-1,4-diamine, were chosen for this purpose. The resulting salts, namely propane-1,3-diaminium N,N'-dinitroethylenediazanide, C3H12N22+·C2H4N4O42-, and butane-1,4-diaminium N,N'-dinitroethylenediazanide, C4H14N22+·C2H4N4O42-, crystallize in the orthorhombic space group Pbca and the monoclinic space group P21/n, respectively. The resulting salts display extensive hydrogen-bonding networks because of the presence of ammonium and diazenide ions in the crystal lattice. This results in an enhanced thermal stability and raises the thermal decomposition temperatures to 202 and 221 °C compared to 180 °C for EDNA. The extensive hydrogen bonding present also plays a crucial role in lowering the sensitivity to impact of these energetic salts.

Binary and ternary charge-transfer complexes using 1,3,5-tri-nitro-benzene.

Three binary and one ternary charge-transfer complexes have been made using 1,3,5-tri-nitro-benzene, viz. 1,3,5-tri-nitro-benzene-2-acetylnaphthalene (1/1), C6H3N3O6·C12H10O, (I), 1,3,5-tri-nitro-benzene-9-bromo-anthracene (1/1), C14H9Br·C6H3N3O6, (II), 1,3,5-tri-nitro-benzene-methyl red (1/1), C15H15N3O2·C6H3N3O6, (III) (systematic name for methyl red: 2-{(E)-[4-(di-methyl-amino)-phen-yl]diazen-yl}benzoic acid), and 1,3,5-tri-nitro-benzene-1-naphthoic acid-2-amino-5-nitro-pyridine (1/1/1), C6H3N3O6·C11H8O2·C5H5N3O2, (IV). All charge-transfer complexes show alternating donor and acceptor stacks, which have weak C-H⋯O hydrogen bonds perpendicular to the stacking axis. In addition, complex (IV) is a crystal engineering attempt to modify the packing of the stacks by inserting a third mol-ecule into the structure. This third mol-ecule is stabilized by strong hydrogen bonds between the carb-oxy-lic acid group of the donor mol-ecule and the pyridine acceptor mol-ecule.

Pharmaceutical hydrates under ambient conditions from high-pressure seeds: a case study of GABA monohydrate.

The monohydrate form of the neurotransmitter γ-amino butyric acid (GABA) has been crystallised in the 0.4-0.8 GPa pressure range, recovered to ambient pressure and then used as a seed. Theoretical calculations indicate that this hydrate is only thermodynamically favoured over the two anhydrous forms at high pressures.

Formation of isostructural solid solutions in 2,6-disubstituted N-phenylformamides and N-phenylthioamides.

In order to investigate possible isostructural solid solutions of disubstituted N-phenylformamides and thioamides, we have studied the re-crystallization of pairs of compounds selected from 2,6-difluoro-N-phenylformamide (I), 2,6-dichloro-N-phenylformamide (II), 2,6-dimethyl-N-phenylformamide (III), 2,6-dichloro-N-phenylthioamide (IV), 2,6-dimethyl-N-phenylthioamide (V), 2,6-diisopropyl-N-phenylformamide (VI) and 2,6-diisopropyl-N-phenylthioamide (VII). For single-component 2,6-disubstituted-N-phenylformamides only the trans form occurs in the pure crystal, while for thioamides the cis form occurs, with only one exception. By forming solid solutions of pairs of these molecules the resulting structures all adopt similar N-H...O/S chains in the crystals. Solid solutions (1), (2) and (3), resulting from the mixing of (I) and (II), (II) and (III), and (IV) and (V), respectively, are all isostructural with each other (space group Pbca). Only co-crystal (1) is isostructural to both starting materials, while (2) is isostructural to only one of the starting pair, (II). Solid solution (3), which adopts the same Pbca structure as (1) and (2), is different to the monoclinic structures of both the reactants. Solid solution (4) is monoclinic, with similar hydrogen-bonded chains, and isostructural to the two components, resulting from the composition from the mixing of (VI) and (VII). Isostructural indices were used to quantify crystal-packing similarities and differences. Occupancy factors of the reactants in each co-crystal differ widely.

The structure lacuna.

Molecular symmetry is intimately connected with the classical concept of three-dimensional molecular structure. In a non-classical theory of wave-like interaction in four-dimensional space-time, both of these concepts and traditional quantum mechanics lose their operational meaning, unless suitably modified. A required reformulation should emphasize the importance of four-dimensional effects like spin and the symmetry effects of space-time curvature that could lead to a fundamentally different understanding of molecular symmetry and structure in terms of elementary number theory. Isolated single molecules have no characteristic shape and macro-biomolecules only develop robust three-dimensional structure in hydrophobic response to aqueous cellular media.

N-(2,6-Diisopropyl-phen-yl)thio-amide.

In the crystal structure of the title compound, C(13)H(19)NS {systematic name: N-[2,6-bis-(propan-2-yl)phen-yl]carbothio-amide}, mol-ecules assemble via N-H⋯S=C hydrogen bonds into helical chains along the b axis. The thio-amide moiety, with a syn disposition of the N- and C-bound H atoms, is twisted out of the plane of the benzene ring to which it is connected, forming a dihedral angle angle of 77.60 (14)°.

N-[(2Z,4Z)-4-Benzyl-idene-6-chloro-1,4-dihydro-pyrido[2,3-d][1,3]thia-zin-2-yl-idene]benzamide.

In the crystal structure of the title compound, C(21)H(14)ClN(3)OS, mol-ecules assemble into inversion dimers via pairs of N-H⋯N hydrogen bonds involving the N-H hydrogen of the thia-zine ring and the N atom of the pyridine ring. There is a close intra-molecular contact [2.570 (2) Å] between the carbonyl O atom of the benzamide and the S atom of the puckered thia-zine ring. The title compound can exist in two tautomeric forms, viz. amino or imino. The observed structure is compatible with the imino form on the basis of observed residual electron density and the two C-N bond lengths of 1.308 (2) and 1.353 (2) Å.

Bis(adamantan-1-aminium) carbonate.

In the title compound, 2C(10)H(18)N(+)·CO(3) (2-), the adamantan-1-aminium cation forms three N-H⋯O hydrogen bonds to three carbonate ions, resulting in a layer parallel to (001) with the adamantane groups located on its surface so that adjacent layers form only C-H⋯H-C contacts. The carbonate anions occupy special positions of 32 symmetry, whereas the adamantan-1-aminium cations occupy special positions of 3 symmetry.

Isonicotinamide-2-naphthoic acid (1/1).

In the title 1:1 adduct, C(6)H(6)N(2)O·C(11)H(8)O(2), the amide group is slightly twisted out of the plane of the aromatic ring, with a C-C-C-N torsion angle of 25.11 (19)°, whereas the carb-oxy-lic acid group is approximately coplanar with the bicylic ring system, with a C-C-C-O torsion angle of 10.9 (2)°. The amide groups from two isonicotinamide mol-ecules form a dimer via N-H⋯O hydrogen bonds. In addition, the 2-naphthanoic acid mol-ecule is hydrogen bonded to the pyridine unit of an isonicotinamide mol-ecule via an O-H⋯N hydrogen bond. This gives rise to a centrosymmetric four-mol-ecule chain, which is cross-linked by further N-H⋯O hydrogen bonds from the amide group.

1-(6-Ferrocenylhex-yl)-1H-imidazole.

The title compound, [Fe(C(5)H(5))(C(14)H(19)N(2))], is characterized by a ferrocenyl group separated from an imidazole functionality by a straight-chain hexyl unit. The two cyclo-penta-dienyl rings of the ferrocenyl group show a marginal inward tilt of 2.17 (2)°. The imidazole unit, which is essentially planar (with a maximum deviation of 0.007 A for one of the N atoms) and tilted away from the ferrocenyl group [dihedral angle between the substituted ferrocenyl ring and the imidazole = 122.6 (1)°], is involved in inter-molecular C-H⋯N inter-actions.

Two polymorphs of N-(2,6-difluorophenyl)formamide.

The structures of two distinct polymorphic forms of N-(2,6-difluorophenyl)formamide, C(7)H(5)F(2)NO, have been studied using single crystals obtained under different crystallizing conditions. The two forms crystallize in different space groups, viz. form (Ia) in the orthorhombic Pbca and form (Ib) in the monoclinic P2(1) space group. Each polymorph crystallizes with one complete molecule in the asymmetric unit and they have a similar molecular geometry, showing a trans conformation with the formamide group being out of the plane of the aromatic ring. The packing arrangements of the two polymorphs are quite different, with form (Ia) having molecules that are stacked in an alternating arrangement, linked into chains of N-H...O hydrogen bonds along the crystallographic a direction, while form (Ib) has its N-H...O hydrogen-bonded molecules stacked in a linear fashion. A theoretical study of the two structures allows information to be gained regarding other contributing interactions, such as pi-pi and weak C-H...F, in their crystal structures.

N-(2,6-Dibromophenyl)formamide.

In the crystal structure of the title compound, C(7)H(5)Br(2)NO, molecules related by translation are linked through N-H...O hydrogen bonds to form chains in the crystallographic a direction, with the aryl rings stacked parallel to each other along the chain. Besides the N-H...O hydrogen bonds, Br...O and Br...Br intermolecular interactions complete the packing of molecules in the crystal structure.

Polymorphs of gabapentin.

Gabapentin [or 1-(aminomethyl)cyclohexaneacetic acid], C(9)H(17)NO(2), exists as a zwitterion [1-(ammoniomethyl)cyclohexaneacetate] in the solid state. The crystal structures and bonding networks of two new monoclinic polymorphs (beta-gabapentin and gamma-gabapentin) are studied and compared with a previously reported gabapentin polymorph [alpha-gabapentin: Ibers (2001). Acta Cryst. C57, 641-643]. All three polymorphs have extensive networks of hydrogen bonds between the NH(3)(+) and COO(-) groups of neighbouring molecules. In beta-gabapentin, there is an additional weak intramolecular hydrogen bond.

Cocrystal of cis- and trans-N-phenylformamide.

N-Phenylformamide, C(7)H(7)NO, crystallizes with two molecules in the asymmetric unit which have different conformations of the formylamino group, one being cis and the other trans. This is the first example of an arylformamide crystal containing both conformational isomers and it may thus be considered a cocrystal of the two conformers. The two molecules in the unit cell are linked through N-H...O hydrogen bonding to two other molecules, thereby forming hydrogen-bonded tetramers within the crystal structure.

A new polymorph of ortho-ethoxy-trans-cinnamic acid: single-to-single-crystal phase transformation and mechanism.

The alpha-polymorph of ortho-ethoxy-trans-cinnamic acid (OETCA) undergoes a reversible single-crystal-to-single-crystal phase transformation at 333 K. The new high-temperature polymorph (alpha'-OETCA) is stable between 333 and 393 K with three molecules in the asymmetric unit (Z' = 3), space group P1;. Unlike the other polymorphs (and solvate) of OETCA recently reported, two of the molecules in alpha'-OETCA deviate significantly from planarity. This conformational change results in the corrugated sheet-type structure of alpha'-OETCA. The sheets are made up of ribbons, each composed of R(2)(2)(8) hydrogen-bonded pairs (via the -COOH groups), which are further connected by CH.O interactions. When exposed to UV radiation the alpha'-OETCA polymorph can be stabilized below 333 K with ca 8% of the monomer converted into the photodimer. The crystal structures of alpha'-OETCA are reported at two temperatures above the phase transition point (at 345 and 375 K) as well as the stabilized forms at 173 and 293 K. A mechanism for the phase transition involving a cooperative conformational transformation coupled with a shift of layers of OETCA molecules is proposed. The alpha'-OETCA polymorph is also an example of a cinnamic acid derivative where two different potentially photoreactive environments exist in one crystal in which each unit cell has two non-centrosymmetric predimer sites and one centrosymmetric predimer site.

Solid-state reaction study of the trans-to-cis isomerization of (eta-C(5)H(4)Me)Re(CO)[P(OPh)(3)]Br(2): a new mechanism for the isomerization reaction.

Single-crystal X-ray structures have been determined at intermediate stages in the single-crystal to single-crystal trans-to-cis thermal isomerization of (eta(5)-C(5)H(4)Me)Re(CO)[P(OPh)(3)]Br(2) at 150 degrees C. Unit cell parameters and site occupancy factors linked to the induced disorder were monitored and found to follow first-order kinetics in the initial (fast component) stage of the reaction. A rate constant of 30 x 10(-6) s(-1) (0.11 h(-1)) was obtained to first-order approximation for the reaction. The irreversibility of the isomerization from single crystals of the cis form was also confirmed. Fourier and difference Fourier maps suggest a novel 2-fold rotation mechanism for the trans-to-cis isomerization reaction. This mechanism entails a unidirectional anticlockwise movement of the CO ligand and only one Br atom.

Interaction of Triphenyltin Hydride and Rhodium. Structure of [Rh(NCBPh(3))(H)(SnPh(3))(PPh(3))(2)] and NMR ((1)H, (15)N, (31)P, (103)Rh, (119)Sn) Study of Pyridine-Containing Derivatives.

The structure of [Rh(NCBPh(3))(H)(SnPh(3))(PPh(3))(2)] (1) (formed from [Rh(NCBPh(3))(PPh(3))(3)] and Ph(3)SnH) was determined by a single-crystal X-ray diffraction study which shows the geometry to be equally well described as a distorted tetragonal pyramid with tin at the apex or a distorted trigonal bipyramid with a hydrogen of one of the phosphine phenyl groups occupying the sixth coordination site. The tin-hydride distance of 2.31(5) Å is consistent with a weak interaction. Crystal data for 1: space group, P2(1)/c; a = 12.564(4), b = 26.942(4), c = 18.000(3) Å; beta = 92.93(2) degrees; V = 6085(2) Å(3); Z = 4; R = 0.050 for 5655 reflections with I >/= 2sigma(I). Complex 1 reacts with pyridine and substituted pyridines L (L = pyridine (py) (a), 4-(dimethylamino)pyridine (4-Me(2)Npy) (b), and 4-carbomethoxypyridine (4-MeO(2)Cpy) (c)) in dichloromethane at -25 degrees C to give trans-[Rh(NCBPh(3))(H)(SnPh(3))(PPh(3))(2)(L)] (2a-c). With L = 4-Me(2)Npy, the products cis-[Rh(NCBPh(3))(H)(SnPh(3))(PPh(3))(2)(4-Me(2)Npy)] (3) and cis- and trans-[Rh(NCBPh(3))(H)(SnPh(3))(PPh(3))(4-Me(2)Npy)(2)] (4 and 5, respectively) are also formed. At room temperature, [Rh(NCBPh(3))(H)(SnPh(3))(PPh(3))(L)] (6a-c) is the final product, decomposing over a period of hours. The pyridine-containing complexes were not isolated and were characterized by NMR spectroscopy, which showed the magnitude of the spin coupling constant J(Sn-H) to increase by factors of up to 5.5 compared with the value of 29 Hz observed for 1. At 50 degrees C, 6 (in the presence of L and PPh(3) originating from 1) undergoes reductive elimination of Ph(3)SnH to give cis-[Rh(NCBPh(3))(PPh(3))(2)(L)]; at this temperature 1 is stable, decomposing only at temperatures of 85 degrees C and above. A kinetic study of the dissociation of Ph(3)SnH from 6b (L = 4-Me(2)Npy) gave activation parameters DeltaH() = 97 +/- 6 kJ mol(-)(1) and DeltaS() = 1 +/- 20 J K(-)(1) mol(-)(1). The weakened interaction between Ph(3)SnH and rhodium is accounted for in terms of a three-center "agostic" bond.