Toluene Hemisolvate Research Articles

Crystal structures of two solvated 2-aryl-3-phenyl-2,3-di-hydro-4H-pyrido[3,2-e][1,3]thia-zin-4-ones.

The synthesis and crystal structures of 2-(4-fluoro-phen-yl)-3-phenyl-2,3-di-hydro-4H-pyrido[3,2-e][1,3]thia-zin-4-one toluene hemisolvate (1), C19H13FN2OS·0.5C7H8, and 2-(4-nitro-phen-yl)-3-phenyl-2,3-di-hydro-4H-pyrido[3,2-e][1,3]thia-zin-4-one iso-propanol 0.25-solvate 0.0625-hydrate (2), C19H13N3O3S·0.25C3H7O·0.0625H2O, are reported. Both are racemic mixtures (centrosymmetric crystal structures) of the individual com-pounds and incorporate solvent mol-ecules in their structures. Compound 2 has four thia-zine mol-ecules in the asymmetric unit. All the thia-zine rings in this study show an envelope pucker, with the C atom bearing the substituted phenyl ring displaced from the other atoms. The phenyl and aryl rings in each of the mol-ecules are roughly orthogonal to each other, with dihedral angles of about 75°. The extended structures of 1 and 2 are consolidated by C-H⋯O and C-H⋯N(π), as well as T-type (C-H⋯π) inter-actions. Parallel aromatic ring inter-actions (π-π stacking) are observed only in 2.

Structural Diversity of Brexpiprazole and Related Analogues: Impact on Solubility and Drug Delivery

Brexpiprazole (BPZ) is an atypical antipsychotic drug indicated for the treatment of schizophrenia and depression. Crystal form screening of BPZ resulted in the formation of three polymorphs (I, II, and III), two methanol solvates, a toluene hemisolvate, and a dihydrate. Thermal analysis and solvent-mediated conversion experiments of the three unsolvated polymorphs established that Form I is the thermodynamically stable form at ambient temperature. All three polymorphs are monotropically related, whereby Forms I and II are the most and least stable forms, respectively. Structural diversity of BPZ was compared with two chemically related analogues, aripiprazole (APZ) and its active metabolite dehydro-aripiprazole (dAPZ). Like APZ and dAPZ, BPZ was shown to form a thermodynamically stable, hydrated crystal form when exposed to an aqueous environment; however, while APZ and dAPZ were characterized as monohydrates, BPZ is a dihydrate. The crystal structure of BPZ dihydrate (S2H2O) showed two water molecules c...

Role of halogen-halogen contacts in the crystal structures of three new solvates of the drug oxyclozanide.

Halogen-halogen contacts are electrostatic in nature and exhibit directionality similar to hydrogen bonds. Oxyclozanide [systematic name: 2,3,5-trichloro-N-(3,5-dichloro-2-hydroxyphenyl)-6-hydroxybenzamide] is a drug used for the treatment of fascioliasis in domestic animals. The molecule carries five chlorine substituents and represents an ideal candidate for the study of halogen bonds in the crystal. Three new crystalline solvates of oxyclozanide, namely, oxyclozanide benzene hemisolvate, C13H6Cl5NO3·0.5C6H6, (I), oxyclozanide xylene hemisolvate, C13H6Cl5NO3·0.5C8H10, (II), and oxyclozanide toluene hemisolvate, C13H6Cl5NO3·0.5C7H8, (III), were structurally characterized. In this context, the crystal structure of oxyclozanide chlorobenzene hemisolvate, C13H6Cl5NO3·0.5C6H5Cl, (IV), was redetermined based on intensity data collected at 100 K. In all four solvates, the cocrystallized solvent molecules are located on crystallographic inversion centres. Solvates (I)-(IV) exhibit similar one-dimensional hydrogen-bonded chains generated by O-H...O, O-H...Cl and Cl...Cl interactions. The extension of these one-dimensional chains into two-dimensional layers is promoted by Cl...Cl and C-H...π contacts. Solvates (III) and (IV) are isostructural and differ from (I) and (II) with respect to subtle details concerning the intermolecular contacts.

The preparation, characterization, structure and dissolution analysis of apremilast solvatomorphs.

Apremilast (AP) {systematic name: (S)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4-acetamidoisoindoline-1,3-dione} is an inhibitor of phosphodieasterase-4 (PDE4) and is indicated for the treatment of adult patients with active psoriatic arthritis. The ability of AP to form solvates has been investigated and three solvatomorphs of AP, namely, the AP ethyl acetate hemisolvate, C22H24N2O7S·0.5C4H8O2, the AP toluene hemisolvate, C22H24N2O7S·0.5C7H8, and the AP dichloromethane monosolvate, C22H24N2O7S·CH2Cl2, were obtained. The three AP solvatomorphs were characterized by X-ray powder diffraction, thermogravimetric analysis and differential scanning calorimetry. Single-crystal X-ray diffraction was used to analyze the structures, crystal symmetry, packing modes, stoichiometry and hydrogen-bonding interactions of the solvatomorphs. In addition, dissolution analyses were performed to study the dissolution rates of different AP solvatomorph tablets in vitro and to make comparisons with commercial apremilast tablets (produced by Celgene); all three solvatomorphs showed similar dissolution rates and similar values of the similarity factor f2 in a comparison of their dissolution profiles.

Crystal structures of three substituted 3-aryl-2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-ones.

Three ring-substituted 3-aryl analogs of 2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one, namely 3-(4-meth-oxy-phen-yl)-2-phenyl-4H-1,3-benzo-thia-zin-4-one, C21H17NO2S, (I), 2-phenyl-3-[4-(tri-fluoro-meth-yl)phen-yl]-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one toluene hemisolvate, C21H14F3NOS·0.5C7H8, (II), and 3-(3-bromo-phen-yl)-2-phenyl-2,3-di-hydro-4H-1,3-benzo-thia-zin-4-one toluene hemisolvate, C20H14BrNOS·0.5C7H8, (III), were synthesized and their crystal structures determined. The hemisolvates differ in that in (II), the asymmetric unit comprises two molecules of the benzo-thia-zinone compound and a toluene solvent mol-ecule, whereas in (III), the unit comprises one benzo-thia-zinone mol-ecule and a half-occupancy toluene solvent mol-ecule. All crystals are of racemic mixtures of the chiral 2-C atom of the thia-zine moiety, which in all structures has a screw-boat puckering, with the puckering amplitude values within the range 0.575-0.603 Å. In all three structures, the benzene plane of the benzo-thia-zine system makes a dihedral angle in the range 78.60 (5) to 98.40 (5)° with the unsubstituted benzene plane and in the range 70.50 (1) to 121.00 (5)° with the substituted benzene plane. The CF3 substituent group in one of the mol-ecules of (II) shows positional disorder, with an occupancy ratio of 0.57 (3):0.43 (3). In the crystals of (I) and (II), weak inter-molecular C-H⋯O inter-actions are present, giving in (I), mol-ecules arranged in a plane parallel to (010), and in (II), chains along a. In addition, all three structures show weak C-H⋯π inter-actions involving various aromatic rings.

Monitoring photo-induced transformations in crystals of 2,6-difluorocinnamic acid under ambient conditions.

Several conditions need to be fulfilled for a photochemical reaction to proceed in crystals. Some of these conditions, for example, geometrical conditions, depend on the particular type of photochemical reaction, but the rest are common for all reactions. The mutual directionality of two neighbouring molecules determines the kind of product obtained. The influence of temperature on the probability of a photochemical reaction occurring varies for different types of photochemical reaction and different compounds. High pressure imposed on crystals also has a big influence on the free space and the reaction cavity. The wavelength of the applied UV light is another factor which can initiate a reaction and sometimes determine the structure of a product. It is possible, to a certain degree, to control the packing of molecules in stacks by using fluoro substituents on benzene rings. The crystal and molecular structure of 2,6-difluorocinnamic acid [systematic name: 3-(2,6-difluorophenyl)prop-2-enoic acid], C9H6F2O2, (I), was determined and analysed in terms of a photochemical [2 + 2] dimerization. The molecules are arranged in stacks along the a axis and the values of the intermolecular geometrical parameters indicate that they may undergo this photochemical reaction. The reaction was carried out in situ and the changes of the unit-cell parameters during crystal irradiation by a UV beam were monitored. The values of the unit-cell parameters change in a different manner, viz. cell length a after an initial increase starts to decrease, b after a decrease starts to increase, c increases and the unit-cell volume V after a certain increase starts to decrease. The structure of a partially reacted crystal, i.e. containing both the reactant and the product, namely 2,6-difluorocinnamic acid-3,4-bis(2,6-difluorophenyl)cyclobutane-1,2-dicarboxylic acid (0.858/0.071), 0.858C9H6F2O2·0.071C18H12F4O4, obtained in situ, is also presented. The powder of compound (I) was irradiated with UV light and afterwards crystallized [as 3,4-bis(2,6-difluorophenyl)cyclobutane-1,2-dicarboxylic acid toluene hemisolvate, C18H12F4O4·0.5C7H8] in a space group different from that of the crystal containing the in-situ dimer.

A dinuclear zinc complex containing a diamond-core geometry: [Zn2(μ2-GueO)2(GueO)2(py)2]·0.5(toluene) (GueOH is guethol)

The title zinc alkoxide, bis(μ-2-ethoxyphenolato)-κ(3)O(1),O(2):O(1);κ(3)O(1):O(1),O(2)-bis[(2-ethoxyphenolato-κ(2)O(1),O(2))(pyridine-κN)zinc(II)] toluene hemisolvate, [Zn2(C8H9O2)4(C5H5N)2]·0.5C7H8, crystallizes with two independent complex molecules located on inversion centres and one independent toluene solvent molecule disordered about an inversion centre. The Zn(II) atoms are six-coordinated in distorted octahedral geometries with O5N donor sets. The Zn(II) ions and bridging alkoxide groups are arranged in a diamond Zn2O2 core structure. The guetholate (2-ethoxyphenolate) ligands adopt two different coordination modes, viz. peripheral chelating and μ2-bridging. Preliminary investigations of the catalytic activity of the compound in the ring-opening polymerization of L-lactide demonstrate rapid and efficient generation of polylactide.

Polymorphs and Solvates of Nicardipine Hydrochloride. Selective Stabilization of Different Diastereomeric Racemates

Molecular understanding of the drug nicardipine hydrochloride (NHc) is provided within this study. For this reason, the polymorphism and crystal structures, including stereochemistry, of the known and the new discovered polymorphs of NHc are discussed. Three new crystalline forms of the nicardipine hydrochloride drug have been isolated: (i) a bishydrated phase, (ii) a chloroform solvate and (iii) a toluene hemisolvate. The crystal structures of these new solvated phases and those of the previously known α and β polymorphs have been determined from conventional single-crystal X-ray diffraction analysis (α phase and chloroform solvate) or from high quality powder X-ray diffraction data using direct-space methods (β phase, bishydrate and toluene hemisolvate). The analysis of the crystal structures revealed that nicardipine hydrochloride crystallizes, in all studied phases, as a racemate with the organic moiety adopting different diastereoisomeric configurations (addressed by the presence of two stereocenters, the C1 and N3 atoms) depending on the actual solvent or polymorph. The chirality of the protonated nicardipine molecules is driven, in the solids, by the strong electrostatic interactions between chloride ions and the protonated nitrogen atoms, which result, in the α phase and in the chloroform solvate, in centrosymmetric dimers built by R,R and S,S molecules. At variance, the β polymorph contains R,S and S,R molecules, still arranged in dimers, but possessing a markedly different molecular shape. Interestingly, in the bishydrated and toluene hemisolvate phases, a slightly disordered crystal structure about the positively charged ammonium group is formed, and both diasteroisomeric couples are present (although with different site occupation factors).

Titanium complexes with sulfur-linked bis(phenolate) ligands

High-quality crystals of two bis(phenolate)titanium complexes, namely dichlorido{4,4'-dimethyl-2,2'-[cyclohexane-1,2-diylbis(sulfanediyl)]diphenolato}titanium(IV), [Ti(C(20)H(22)O(2)S(2))Cl(2)], (I), and dichlorido{2,2'-[cyclohexane-1,2-diylbis(sulfanediyl)]diphenolato}titanium(IV), [Ti(C(18)H(18)O(2)S(2))Cl(2)], (II), were obtained by reactive crystallization. Depending on the solvent, compound (II) was obtained as unsolvated (IIa) or as the toluene hemisolvate, [Ti(C(18)H(18)O(2)S(2))Cl(2)].0.5C(7)H(8), (IIb). These systems without bulky substituents on the aromatic phenolate rings serve as ideal model compounds for precatalysts. The excellent X-ray diffraction data will help clarify the nature of the mismatched interactions between the soft S atoms within the ligand and the hard titanium center. Molecule (I) has crystallographic C(2) symmetry.

New Toluene Hemi Solvate of the Proton Pump Inhibitor Piperazinium Esomeprazolate

The new toluene hemisolvate of the piperazinium salt of esomeprazole, ((S)-5-methoxy-2-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methylsulfinyl]-3H-benzimidazole, C17H19N3O3S) has the composition piperazinium esomeprazolate 0.5 toluene. The unit cell has monoclinic P21 symmetry with the cell parameters a = 10.0903(16) A, b = 16.234(3) A, c = 15.316(2) A, β = 92.746(12)°, V = 2,506.0(7) A3. It contains four piperazinium, four esomeprazolate and two toluene molecules. The crystal structure exhibits intermolecular hydrogens bonds within the layers and Van der Waals contacts between the layers. Additionally, three new crystal phases of solvent-free piperazinium esomeprazolate were found. The title compound is a toluene hemisolvate of the piperazinium salt of esomeprazole, ((S)-5-methoxy-2-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methylsulfinyl]-3H-benzimidazole. Single crystal X-ray diffraction analysis reveals that the molecules crystallize in layers. In a layer the molecules are held together by classical hydrogen bonds whereas the layers on the other hand are connected by vdW contacts.

Mu-Bis(diphenylphosphino)methane-P:P'-octacarbonyldimanganese(Mn-Mn) and its toluene hemisolvate.

The Mn-Mn bonds in the two independent molecules of the unsolvated title compound, [Mn(2)(C(25)H(22)P(2))(CO)(8)], (I), are 2.9714 (7) and 2.9746 (7) A. This bond is distinctly shortened in the toluene hemisolvate, [Mn(2)(C(25)H(22)P(2))(CO)(8)] x 0.5C(7)H(8), (II), to 2.9338 (14) A and this shortening is accompanied by an increase in magnitude of the P-Mn-Mn-P torsion angle [26.93 (3) and 28.44 (3) degrees in (I), and 33.25 (7) degrees in (II)], while the P...P 'bite' is much less affected [3.092 (2) and 3.099 (2) A in (I), and 3.091 (3) A in (II)]. The toluene solvate molecule in (II) lies on a twofold axis.

N,N'-(1,2-phenylene)bis(pyridine-2-carboxamide) and N,N'-(1,2-cyclohexanediyl)bis(pyridine-2-carboxamide) toluene hemisolvate.

The crystal structures of N,N'-(1,2-phenylene)bis(pyridine-2carboxamide), C 18 H 14 N 4 O 2 , (I), and N,N'-(1,2-cyclohexane-diyl)bis(pyridine-2-carboxamide) have been determined, the latter compound as the toluene hemisolvate, C 18 H 20 N 4 O 2 .0.5C 7 H 8 , (II). In (I), the benzene ring is nearly coplanar with one of the pyridine rings and forms a dihedral angle of 59.4 (1)° with the other. However, in (II), the dihedral angle of the two pyridine rings is 70.0 (1)°.

Synthetic, Structural, Mechanistic, and Theoretical MO Studies of the Alkali-Metal Chemistry of Dibenzylamine and Its Transformation to 1,3-Diphenyl-2-azaallyl Derivatives

Dibenzylamido anions ((PhCH(2)N-) can be transformed into 1,3-diphenyl-2-azaallyl anions ({PhC(H)-N-C(H>Ph}(-)) by the assistance of PMDETA- ((Me(2)NCH(2)CH(2))(2)NMe) complexed Li+, Na+, or K+ cations. The heavier alkali-metal cations give only the trans,trans conformation of the azaallyl anion, in contrast to the lighter Li+ cation, which yields two crystalline conformers, the trans,trans and an unknown species, Ab initio MO geometry optimizations on model Li and Na complexes intimate that it is the relative tightness of the contact ion pair structures which dictates this distinction with Li+ having more influence on the conformation and stability of the anion than Na+, which forms a much looser contact ion pair more akin to the ''free'' anion, On the basis of kinetic H-1 NMR studies, combined with X-ray crystallographic data, the amido --> azaallyl conversion can be explained in terms of a two-step process involving beta-elimiqation of a metal hydride followed by hydride metalation of the produced imine PhCH(2)N=C(H)Ph. This process appears to be initiated by deaggregation of the metallodibenzylamine to an intermediate monomeric structure, accomplished by solvation. The nature and degree of solvation required depend on the particular M(+) cation involved. Three new crystal structures are revealed in the course of this study. All are based on familiar four-membered (N-M)(2) rings, but whereas the sodium complex [{(PhCH(2))(2)NNa.TMEDA}(2)] and the lithium complex [{(PhCH(2))(2)NLi.THF}(2)] are both discrete dimers, unique [{[(PhCH(2))(2)NLi](2).(dioxane)}infinity], isolated as its toluene hemisolvate, is a polymer composed of linked dimeric units and so is the first dibenzylamido alkali-metal species to have an infinitely extended structure.

Comparison of the structures of two trimesityltin iodide solvates and triphenyltin iodide

The structures of iodotris(2,4,6-trimethylphenyl)tin(IV) trichloro( 2 H)methane hemisolvate, [SnI(C 9 H 11 ) 3 ].CDCl 3 (I), iodotris(2,4,6-trimethylphenyl)tin(IV) toluene hemisolvate, [SnI(C 9 H 11 ) 3 ] 2 .C 7 H 8 (II), and iodotriphenyltin(IV), [SnI(C 6 H 5 ) 3 ] (III), have been determined by single-crystal X-ray diffraction. All three crystallize in the same space group (P1) with Ar 3 SnI molecules forming chains through the lattice using overlapping aryl groups. In (III), these are closely packed, but in (I) and (II), p-CH 3 groups prevent this, leaving voids which are filled by solvent molecules

Cyclopentadienyldifluorphosphin und Homologe als Liganden in cis-Dichloroplatin(II)-Komplexen — Struktur von cis-(C5Me5PF2)2PtCl2 und cis-(C9H7PF2)[(C9H7)3P]PtCl2 (C5Me5 = Pentamethylcyclopentadienyl, C9H7 = Indenyl) / Cyclopentadienyldifluorophosphine and its Homologues as Ligands in cis-Dichloroplatinum(II) Complexes — Structure of cis-(C5Me5PF2)2PtCl2 and cis-(C9H7PF2)[(C9H7)3P]PtCl2 (C5Me5 = Pentamethylcyclopentadienyl, C9H7 = Indenyl)

Derivatives of cyclopentadienyldifluorophosphine. e. g. CpPF2 (1), Cp*PF2 (Cp* = C5Me5) (2),1-(indenyl)PF2 (3), 9-(fluorenyl)PF2 (4), 1-(ferrocenyl)PF2 (5), 1,1′-(ferrocenyl)(PF2)2 (6) and also 1-N-phenyl-2-difluorophosphinopyrrole (7) were prepared using the reaction of the appropriate organolithium compound and PF2Cl. Their reactivity towards cis-dichloro-(η4-cyclooctadiene)-platinum(II) and tetracyanoethylene was investigated. The complexes poly-dichloro-bis-(cyclopentadienyldifluorophosphine)platinum(II) (8), cis-dichloro-bis-(pentamethylcyclopentadienyldifluorophosphine)platinum(II) (9), cis-dichloro-(3-indenyldifluorophosphine)(di(1-indenyl)-3-indenylphosphine)platinum(II) (10), cis-dichloro-bis-(9-fluorenyldifluorophosphine)platinum(II) (11) and cis-dichloro-bis-(1-N-phenyl-2-difluorophosphinopyrrole)platinum(II) (12) were prepared. 10 is the first mixed organodifluorophosphine-triarylphosphine-platinum(II)-complex. The structures of 9 and 10 were determined by X-ray crystal structure analyses. 9 crystallizes in the monoclinic space group, P21/c with cell constants a = 835.3(2), b = 1479.0(3), c = 2071.7(4) pm, β = 99.67(2)° and Z = 4; R = 0.038 for 4760 unique observed reflections. The bonds to platinum are all short; Pt—P 220.3, 219.8(1), Pt—Cl 231.7, 231.9(2) pm. 10 crystallizes as a toluene hemisolvate in the monoclinic space group, P21/n, with cell constants a = 1225.7(5), b = 995.0(3), c = 2886.3(10) pm, β = 90.83° and Z = 4; R = 0.074 for 2664 unique observed reflections. The precision was poor, but the unexpected presence of both 1- and 3-indenyl groups was unambiguously demonstrated.

Structure and molecular orbital study of ergoline derivatives. 1-(6-Methyl-8 beta-ergolinylmethyl)imidazolidine-2,4-dione (I) and 2-(10-methoxy-1,6-dimethyl-8 beta-ergolinyl)ethyl 3,5-dimethyl-1H-2-pyrrolecarboxylate toluene hemisolvate (II) and comparison with nicergoline (III).

(I): C19H22N4O2 (Registry No. 95688-34-9), m.p. greater than 573 K, Mr = 338.4, orthorhombic, P2(1)2(1)2(1), a = 8.392 (2), b = 13.004 (2), c = 15.676 (5) A, V = 1710.7 (7) A3, Z = 4, Dx = 1.31 Mg m-3, Mo Ka radiation, lambda = 0.71069 A, mu = 0.08 mm-1, F(000) = 720, T = 293 K, final R = 0.051 for 990 independent reflexions. (II): C26H33N3O3.1/2C7H8 (Registry No. 54370-23-9), m.p. 427-429 K, Mr = 481.64, monoclinic, P2(1), a = 11.595 (4), b = 14.274 (2), c = 16.103 (4) A, beta = 100.19 (3) degrees, V = 2623 (1) A3, Z = 4, Dx = 1.22 Mg m-3, Mo Ka radiation, lambda = 0.71069 A, mu = 0.07 mm-1, F(000) = 1036, T = 293 K, final R = 0.064 for 2738 independent reflexions. Two independent molecules constitute the asymmetric unit, together with a toluene molecule. Parallel investigations of the title compounds by single-crystal X-ray analysis and theoretical calculations have converged in showing an extended configuration of the side chain attached at the C8 atom of the ergoline nucleus.