Demetrius C. Levendis

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.

Searching for novel crystal forms by in situ high-pressure crystallisation: the example of gabapentin heptahydrate

High-pressure crystallisation of an aqueous solution of the GABA analogue gabapentin at 0.8 GPa resulted in the formation of a previously unknown heptahydrate form, whose structure has been determined by in situ single-crystal X-ray diffraction. The structure and water framework of this unusually highly hydrated small molecule are described in detail.

Crystal structure of osmocene, Os(η-C5H5)2

Crystals of osmocene, Os(η-C5H5)2, are orthohombic:Pnma,Mr=321.3,a=7.079(2),b=8.908(1),c=12.771(2),Vc=806 Å3,Z=4,Dx=2.640 g cm−3, MoKα (λ=0.71069 Å),μ=151 cm−1,F(000)=584,T=293 K,R=0.04 for 730 observed reflections. Osmocene is isomorphous with ruthenocene and the molecules have averageD5h symmetry with a mean Os-C distance of 2.19(1) Å (compared with 2.186 Å forRu-C).

Organometallic Chemistry: Structural Isomerization Reactions in Confined Environments

Reactions in the solution phase have dominated the development of chemistry. In recent years, however, the area of solid-state organic chemistry has undergone a renaissance, although the related area of organometallic chemistry is still in its infancy. Indeed, only a limited number of systematic studies on the reactions of organometallic compounds in a confined environment (on a surface, in a zeolite pore, in the bulk phase) have been reported. Herein we summarize some recent results on a specific reaction type in a confined environment, namely the isomerization reaction. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synthesis of ferrocenylphenyl derivatives including biphenylferrocenes, arylferrocenylphenyl ethers and arylferrocenylphenyl amines

The preparation of a series of substituted biphenylferrocenes via a modified Suzuki reaction between 4-bromophenylferrocene and substituted phenylboronic acids is described. The X-ray crystal structure of 4′-formyl-4-biphenylferrocene is reported and this compound is then incorporated into the first series of ferrocenomesogens containing the ferrocenylbiphenyl unit. The synthesis of a series of arylferrocenylphenyl ethers and arylferrocenylphenyl amines is also described.

Polymorphism and phase transformations in 2,6-disubstituted N-phenylformamides: the influence of hydrogen bonding, chloro-methyl exchange, intermolecular interactions and disorder

The crystal structures, thermal behaviour and phase transformations of a series of 2,6-disubstituted-N-phenylformamides have been investigated. A phase transformation was only observed when chlorine was one of the substituents. Crystals of the room-temperature form of 2,6-dichloro-N-phenylformamide (1) and 2-chloro-6-methyl-N-phenylformamide (2) are isomorphous. Both compounds are orthorhombic at room temperature and transform to a monoclinic high-temperature form at 155 and 106 °C, respectively. The room-temperature structures of 1 and 2 consist of chains of N–H⋯O hydrogen-bonded molecules stacked in an alternating arrangement along the crystallographic a direction. The high-temperature forms of compounds 1 and 2 (grown by sublimation) are both monoclinic but not isomorphous, with one short axis of about 4.3 A, and consist of chains of N–H⋯O hydrogen-bonded molecules stacked along the short axis, related by translation. When both of the chlorine substituents are replaced by methyl groups, as in 2,6-dimethyl-N-phenylformamide (3), the crystals do not undergo any phase transition on heating and only an orthorhombic form, space group P212121, has been isolated. Examination of the molecular geometry and structural properties of 3 indicates that it is a hybrid structure of the low- and high-temperature forms of compounds 1 and 2. This contribution analyzes the effect of chloro-methyl exchange, the steering ability of chlorine, and the role of weak interactions on the structural and thermal properties of the compounds studied. In addition, a mechanism for the phase change in 1 is proposed and rationalized through the examination of the structures themselves together with lattice energy calculations.

Substituted cyclopentadienyl complexes: VII. An NMR and X-ray crystallographic study of [(η5-C5H4R)Fe(CO)(PPh3)I] (R = CHPh2, I, CH(CH3)2)☆

The complexes [(η5-C5H4R)Fe(CO)(PPh3)I] (R = I (1), CH(CH3)2 (2), CHPh2 (3)) have been synthesised. The NOE spectra recorded on the new complexes reveal a preferential conformation of the ring substituent on 3, with the H atom of the benzhydryl group pointing towards the PPh3 ligand. A similar effect is not observed in the spectrum of 2. The phenomenon is related to the steric effect associated with the relative sizes of the ring substitutents. The crystal structures of 1 and 3 have been determined. The results for 3 suggest that the dominant conformer observed in solution corresponds to the solid state structure.

A single-crystal-to-single-crystal Diels–Alder reaction with mixed topochemical and topotactic behaviour

Electron donor/acceptor (EDA) interactions have been found to be very useful in engineering reactive heteromolecular crystals, but few examples have been reported in the literature. By utilising EDA interactions, crystals of charge-transfer (CT) complexes were formed with bis(N-allylimino)-1,4-dithiin as the electron acceptor and 9-bromoanthracene as the electron donor. The CT complex crystallised in the monoclinic P21/n space group with the crystal structure consisting of stacks of alternating electron donor and acceptor molecules in a 1 : 1 ratio. These crystals are able to undergo a solid-state Diels–Alder reaction with bis(N-allylimino)-1,4-dithiin as the dienophile and 9-bromoanthracene as the diene. Examination of close contacts indicates that the diene can theoretically react with the dienophile above or below it within a stack as the reaction distances are less than 3.5 A in both directions. A single crystal was selected and allowed to react at 30 °C, was analysed at various states of conversion by single-crystal X-ray diffraction, and was found to react by approximately 10% every 6 days, with the reaction occurring in a single direction along the CT stack axis. The solid-state reaction creates a void space which leads to a molecular conformational change within the crystal. Consequently, the single crystal started to show significant signs of deterioration after approximately 28% conversion but remained intact upon further reaction and was found to anneal as 100% conversion was approached, leading to the formation of new intermolecular interactions not present in the starting crystal. The solid-state reaction occurs topochemically when fewer than 28% or more than 80% of the molecules have reacted, with minimal motion during the reaction. In the conversion range of 28–80%, the reaction occurs in an almost topotactic manner with significant molecular motion and associated crystal deterioration.

A hexagonal solvate of the neurotransmitter γ-aminobutyric acid

A solvated crystal of the neurotransmitter, γ-aminobutyric acid (GABA), crystallized concomitantly with the monoclinic and tetragonal polymorphic forms of GABA. The solvated crystals were isolated and the crystal structure elucidated, showing a hexagonal solvated crystal form of GABA with the ethanol solvent molecules occupying the channels which have a diameter of approximately 4.5 A.

Cocrystal of cis- and trans-N-phenyl- formamide

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.