Crystal Forms of the Antiepileptic Lamotrigine: Molecular Salts and Solvates with Fluorobenzoic Acid,Nicotinic Acid, 2-Thiobarbituric Acid, 3-Picoline and Butyl Alcohol

Abstract  

The crystal structures of three salts and two solvated multicomponent crystals of lamotrigine with 4-fluorobenzoic acid, nicotinic acid, 2-thiobarbituric acid, 3-picoline and butyl alcohol are reported. Compound 1a crystallizes in monoclinc system, space group P2₁ with a = 13.3860(5) ?, b = 8.3420(3) ?, c = 15.5200(6) ?, β = 93.524(1)°, V = 1729.78(11) ?³, and Z = 2. Compound 1b crystallizes in monoclinic system, space group P2₁/c with a = 10.6625(7) ?, b = 16.2575(11) ?, c = 13.6346(9) ?, β = 100.904(1)°, V = 2320.8(3) ?³, and Z = 4. Compound 1c crystallizes in triclinic system, space group P[`1] \overline{1} , with a = 10.1309(7) ?, b = 12.0260(8) ?, c = 14.0826(10) ?, α = 71.783(1)°, β = 86.451(1)°, γ = 80.902(1)°, V = 1609.10(19) ?<sup>3</sup>, and Z = 1. Compound 1d crystallizes in monoclinic system, space group P2<sub>1</sub>/c with a = 14.9570(10) ?, b = 8.0230(6) ?, c = 13.8162(10) ?, β = 102.884(1)°, V = 1616.2(2) ?<sup>3</sup>, and Z = 4. Compound 1e crystallizes in triclinic system, space group P[`1] \overline{1} , with a = 7.5710(6) ?, b = 8.5721(7) ?, c = 13.5532(11) ?, α = 85.364(1)°, β = 79.632(1) (1)°, γ = 86.188(1)°, V = 861.19(12) ?³, and Z = 2. Characteristic R₂²(8) dimer is observed in all five structures. A complete hydrogen bonded motif analysis is described. Lamotrigine-lamotrigine base pair is observed in all the structures, except in (1b). In (1c), the R₂²(7) dimer is noticed while, in all other structures R₂²(8) dimer exist between the lamotrigine-lamotrigine base pair. In all the six structures, chlorine atoms of the lamotrigine molecules are not involved in any interactions.     

The Synthesis and Crystal Structure of 5-Methyl-1-(1-naphthyl)-1,2,3-triazol-4-carboxyl Acid

Abstract  5-Methyl-1-(1-naphthyl)-1,2,3-triazol-4-carboxyl acid 3 was synthesized from 1-aminonaphthalene. The yielded product 3 was investigated with X-ray crystallographic, NMR, MS and IR techniques. Compound 3, C₁₄H₁₁N₃O₂, Mr = 253.26, crystallizes in the orthorhombic space group Pbca with unit cell parameters a = 10.068(2), b = 12.353(2), c = 20.102(4) ?, V = 2500.1(8) ?³, Z = 8, Dx = 1.346 Mgm^-3. The final R was 0.0474. The molecular packing is stabilized by intermolecular O–H···N interactions. Index Abstract  5-Methyl-1-(1-naphthyl)-1,2,3-triazol-4-carboxyl acid 3 was synthesized from 1-aminonaphthalene. The yielded product 3 was investigated with X-ray crystallographic, NMR, MS and IR techniques. Compound 3, C₁₄H₁₁N₃O₂, Mr = 253.26, crystallizes in the orthorhombic space group Pbca with unit cell parameters a = 10.068(2), b = 12.353(2), c = 20.102(4) ?, α = β = γ = 90.00o. V = 2,500.1(8) ?³, Z = 8, Dx = 1.346 Mgm⁻³. The final R was 0.0474. The molecular packing is stabilized by intermolecular O–H···N interactions.      

Synthesis, Crystal Structures and Molecular Packing of a Series of Pyrazolo-Benzothiazine Hybrid Derivatives

Abstract  

The crystal structures of four derivatives of pyrazolo[4,3-c][1,2]benzothiazine-2,4-dihydro-3,4-dimethyl-,5,5-dioxide containing benzothiazine dioxide and pyrazolo fused rings that have been synthesized were determined. (C₁₁ H₁₁ N₃ O₂ S): Mr = 249.29, monoclinic, P2₁/c, a = 8.3070(3), b = 13.6331(5), c = 10.1661(3) ?, β = 106.924(2)°, V = 1101.45(7) ?^3, Z = 4. (C₁₂ H₁₃ N₃ O₂ S): Mr = 263.31, monoclinic, P2₁/n, a = 9.729(3), b = 11.224(4), c = 11.436(3) ?, β = 98.85(2)°, V = 1233.9(7) ?³, Z = 4. (C₁₄ H₁₅ N₃ O₄ S): Mr = 321.35, monoclinic, P2₁/c, a = 9.2534(3), b = 19.3920(7), c = 7.9489(2) ?, β = 95.323(2)°, V = 1420.21(8) ?^3, Z = 4. (C₁₄ H₁₅ N₃ O₃ S): Mr = 305.35, monoclinic, P2₁ /c, a = 13.816(7), b = 7.464(3), c = 14.674(8) ?, β = 109.05(3)°, V = 1430.3(12) ?³, Z = 4. The heterocyclic thiazine rings adopt half-chair conformations, and the mean-planes of the phenyl and pyrazolo rings lie between 10.43(11) and 15.93(16)° with respect to each other. In each case, the geometry about thiazine N-atom is trigonal pyramidal and only the first compound containing a donor N-atom shows classical hydrogen bonds. However, non-classical H-bonding of the type C–H···O is observed in all structures.     

Crystal Structure of <Emphasis Type="Italic">N</Emphasis>-(2-Pyridylmethylene)benzene-1,4-diamine

Abstract  

The crystal structure of amino containing Schiff base, N-(2-pyridylmethylene)benzene-1,4-diamine, was determined via X-ray diffraction analysis. The title compound crystallizes in orthorhombic system, space group Pc2 ₁ n, with unit cell dimensions a = 5.8945(6), b = 11.9233 (10), c = 14.5356 (16) ?, V = 1021.59 (18) ?³, Z = 4. The molecules are linked by intermolecular N–H···N hydrogen bonds to form supramolecular sheets along with the bc crystallographic plane. The crystal structure is further stabilized by C–H···π stacking interactions.     

The Crystal Structure and Conformational Studies of Acridinedione Derivatives

Abstract  

Two crystal structures of acridinediones namely, TMHAD and MPHAD were studied by X-ray crystallographic method in view of their occurrence in numerous commercial products including pharmaceuticals, fragrances and dyes. Crystal data of TMHAD are: C₁₇H₂₃NO₂, orthorhombic, Fdd2, with cell parameters a = 40.417(6) ?, b = 5.744(1) ?, c = 12.979(2) ?, V = 3013.1(7) ?³, Z = 8, D_cal = 1.205 Mg/m³, μ = 0.078 mm⁻¹. Crystal data of MPHAD are: C₂₀H₁₈NO₃; monoclinic, P2₁/c with cell parameters a = 10.182(9) ?, b = 17.105(14) ?, c = 10.895(9) ?, β = 117.857(1)°, V = 1678(2) ?³, Z = 4, D_cal = 1.268 Mg/m³, μ = 0.085 mm⁻¹. Both data were collected using λ (MoK_α) = 0.71073 ?. The central ring in the acridinedione moieties tends to be planar while the outer two rings adopt sofa conformations. Intermolecular interactions of C–H···O type of hydrogen bond help the molecules to stabilize into the crystal packing. Interestingly, a week forces of C–H···π interactions also helps the molecules for stabilization.     

Synthesis and Crystal Structure of New Heterocyclic Compounds Containing 1,2,3-Triazole Moiety

Abstract  

A series of new heterocyclic compounds bearing 1,2,3-triazole moiety were synthesized using 4-acetyl-2-phenyl-1,2,3-triazole 1 as the starting material. The target compounds were prepared and the structures were characterized by IR, ¹H NMR, MS and elemental analysis. Meanwhile, the crystal structures of the synthesized compounds were also furthered confirmed by X-ray diffraction analysis. Compound 3b crystallized in the monoclinic P2(1)/c space group with unit cell parameters a = 10.6974(17) ?, b = 20.356(3) ?, c = 7.8049(12) ?, α = 90°, β = 102.840(3)°, γ = 90o, V = 1657.1(5) ?³, Z = 4, T = 293(2) K. Compound 7c crystallized in the Triclinic P-1 space group with unit cell parameters a = 7.364(2) ?, b = 7.366(2) ?, c = 26.089(8)?, α = 87.114(7)°, β = 87.040(7) (3)°, γ = 82.337(7)°, V = 1399.2(7) ?³, Z = 2, T = 293(2) K. Compound 10c crystallized in the Triclinic P-1 space group with unit cell parameters a = 9.8152(10) ?, b = 10.0806(13) ?, c = 11.1267(14) ?, α = 100.344(3)°, β = 111.975(3)°, γ = 107.852(3)°, V = 916.18(19) ?³, Z = 2, T = 293(2) K.     

Synthesis, Structural Characterization and Spectroscopic Properties of 1,2-Bis[4-(3,5-dimethyl-1H-pyrazol-1-yl)-2-oxobutyl]benzene

Abstract  

The crystal structure of the title compound C₂₂H₃₀N₄O₂·H₂O (L), has been determined using X-ray diffraction at 293 K. The crystal of 1,2-bis[4-(3,5-dimethyl-1H-pyrazol-1-yl)-2-oxobutyl]benzene is in triclinic crystal system with space group P(−1) (Z = 2), lattice parameters a = 8.225(6) ?, b = 10.967(6) ?, c = 12.903(6) ?, V = 1119.1(11) ?³. Analyses of single crystals of L, crystallized from dichloromethane/diethyl ether (1:1), revealed that the molecules are arranged in couples, which adopt a pseudo chair conformation, by means of intermolecular O–H···N hydrogen bonding interactions. Moreover, the extended structure revealed a 1D chain caused by several C–H···N intermolecular interactions.     

Crystal Structures of 5,6,5′,6′-Tetramethoxy-1,1′-spirobisindane-3,3′-dione and two of its Fluorene Adducts

Abstract  

The structures of three spirobisindanes 1, 2a and 2b are reported. Each compound is a precursor to a Polymers of Intrinsic Microporosity (PIM) and is the component that provides the necessary site of contortion within the polymer. Of particular importance are the angles formed between the aromatic units around the spiro-centre as it may have direct relevance to the inefficiency of packing in the solid state packing, we think, induces microporosity in the final polymer. Compound 1 crystallized in the monoclinic P21/c space group with unit cell parameters a = 9.8000(5) Ǻ, b = 17.8710(9) Ǻ, c = 10.4100(5) Ǻ, β = 106.6280(10)°, V = 1746.92(15) A³, Z = 4, D = 1.401 Mg/m³. Compound 2a crystallized in the monoclinic P21/c space group with unit cell parameters a = 9.7460(13) Ǻ, b = 30.291(4) Ǻ, c = 8.6740(12) Ǻ, β = 97.111(3)°, 2541.0(6) A³, Z = 4, D = 1.319 Mg/m³. Compound 2b crystallized in the monoclinic P21/n space group with unit cell parameters a = 13.5670(9) Ǻ, b = 12.7930(8) Ǻ, c = 22.1960(14) Ǻ, β = 96.6630(10)°, V = 3826.4(4) A³, Z = 4, D = 1.265 Mg/m³.     

Synthesis and Crystal Structure of 1,3-Bis[2-(pyrrol-2-carbonyloxy)ethoxy]Benzene

Abstract  

A new compound, 1,3-bis[2-(pyrrol-2-carbonyloxy)ethoxy]benzene (1), was synthesized and characterized by X-ray diffraction. The crystal is monoclinic, space group P2₁/c with a = 6.3571(7), b = 11.0416(11), c = 28.156(3) ?, b = 92.821(2), V = 1974.0(4) ?³, Z = 4, Dc = 1.293 g/cm³, F(000) = 808, μ = 0.097 mm⁻¹. The final R = 0.0395 and wR = 0.0927 for 3478 observed reflections with I > 2 σ(I), and R = 0.0660 and wR = 0.1058 for all reflections. The title compound assembles into 2-D structure through a catemer type N–H⋯O hydrogen bonding motif and further forms 3-D structure through C–H···O hydrogen bonds.     

N–H···π Interactions in Two Isomers of an Amino Group Containing <Emphasis Type="Italic">bis</Emphasis>-Phenol

Abstract  

Crystal structures of two bis-phenols namely bis-(3,5-dimethyl-2-hydroxyphenyl)(3-amino phenyl)methane 1 and bis-(3,5-dimethyl-4-hydroxyphenyl)(3-aminophenyl) methane 2 are determined. The compound 1 crystallises in monoclinic P2₁/c with a = 12.2579(16) ?, b = 16.0906(19) ?, c = 10.6664(13) ?, β = 115.417(7)°, V = 1900.2(4) ?³ whereas 2 crystallizes in monoclinic C2/c, a = 9.2538(2) ?, b = 18.6579(4) ?, c = 23.2725(5) ?, β = 98.796(2)°, V = 3970.89(15) ?³. The crystal lattice of both the compounds shows presence of N–H···π interactions but no O–H···π interactions.     

Inclusion of Caffeine by a Diol Host

Abstract  

The host compound 9,9′-(ethyne-1,2-diyl)-bis(fluoren-9-ol), H, forms inclusion compounds with caffeine (H·CAF) and methanol (H·MeOH). The host and guest ratios were 1:2 and 1:1, respectively. Both of these structures were successfully solved in P-1 with unit cell dimensions for H·CAF: a = 7.2121(14) ?, b = 9.2782(19) ?, c = 15.206(3) ?, α = 73.23(3)°, β = 84.20(3)°, γ = 73.39(3)°, Z = 2 and for H·MeOH : a = 9.7592(10) ?, b = 11.2584(11) ?, c = 20.7854(19) ?, α = 97.161(2)°, β = 99.263(2)°, γ = 95.257(2) ?, Z = 2. These crystal structures were studied together with that of a mixed clathrate, H·CAF·MeOH with stoichiometry 2:1:1.5. For H·CAF·MeOH which was solved in P2₁/c : a = 12.2051(5) ?, b = 46.8023(19) ?, c = 9.0121(4) ?, β = 91.9650(10)°, Z = 4. The kinetics of desolvation of the methanol solvate (H·MeOH) yielded an activation energy of 69.6–83.9 kJ mol⁻¹.     

The Synthesis and Crystal Structure of (4α,8β,13β,16β)-13-Methyl-16,18-diol-17-Norkaurane: A Simultaneous Reduction Product of Isosteviol

Abstract  

(4α,8β,13β,16β)-13-methyl-16,18-diol-17-norkaurane was synthesized by esterification and reduction of isosteviol, respectively. The structure of the title compound was established by spectral analysis and X-ray diffraction studies. The compound crystallizes in the orthorhombic space group P2₁2₁2₁ with unit cell parameters: a = 7.3705 (14) ?, b = 13.508 (3) ?, c = 20.139 (4) ?, V = 2005.1 (7) ?³, Z = 4. The conformation of rings A and B is chair, whereas the conformation of ring C is unsymmetrical distorted chair. The stereochemistry of the A/B and B/C ring junctions is trans, while the five-membered ring D adopts an envelope conformation.     

Synthesis and Crystal Structure of (E)-1-(2,3-Dihydroxybenzlidene)-4,4-Dimethythiosemicarbazide

Abstract  

The Schiff base C₁₀H₁₃N₃O₂S is monoclinic, having unit cell parameters a = 9.788(1) ?, b = 9.615(1) ?, c = 12.605(1) ?, β = 108.41(1)° and V = 1125.56(2) ?³ and belongs to P2_1/n space group. The molecule is almost planar. The two hydroxyl groups present on the phenyl ring are involved in intermolecular H-bonding, which results in the stacking of molecules in the anti-parallel fashion leading an interesting network of channels. Besides this C–H⋯π and π–π (edge to edge) interactions appear to provide stability to the crystal lattice.     

The Synthesis and Crystal Structure of New Bis(3-chlorophenyl)-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-methanol

Abstract  The title compound bis(3-chlorophenyl)-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-methanol 8 has been synthesized and established by H NMR, IR and MS spectra and X-ray diffraction crystallography. Compound 8, C₂₃H₂₉Cl₂N₃O, Mr = 424.31, crystallizes in the monoclinic space group P2₁/c with unit cell parameters a = 14.5402(6) ?, b = 12.5888(5) ?, c = 11.6510(5) ?, α = 90o, β = 100.183o(2), γ = 90o, V = 2099.05(15) ?³, D_x = 1.343 mg m⁻³ and Z = 4. The final R was 0.0514. The molecular conformation and packing is stabilized by interactions of intermolecular O1–H1···N3′. Index Abstract  The structure of bis(3-chlorophenyl)-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-methanol by the reaction of compound 4 and Grignard regent is studied.      

Low Temperature Crystal Structures of Two Rhodanine Derivatives, 3-Amino Rhodanine and 3-Methyl Rhodanine: Geometry of the Rhodanine Ring

Abstract  Rhodanines (2-thio-4-oxothiazolidines) are synthetic small molecular weight organic molecules with diverse applications in biochemistry, medicinal chemistry, photochemistry, coordination chemistry and industry. The X-ray crystal structure determination of two rhodanine derivatives, namely (I), 3-aminorhodanine [3-amino-2-thio-4-oxothiazolidine], C₃H₄N₂OS_2, and (II) 3-methylrhodanine [3-methyl-2-thio-4-oxothiazolidine], C₄H₅NOS₂, have been conducted at 100 K. I crystallizes in the monoclinic space group P2₁/n with unit cell parameters a = 9.662(2), b = 9.234(2), c = 13.384(2) ?, β = 105.425(3)°, V = 1151.1(3) ?³, Z = 8 (2 independent molecules per asymmetric unit), density (calculated) = 1.710 mg/m³, absorption coefficient = 0.815 mm⁻¹. II crystallizes in the orthorhombic space group Iba2 with unit cell a = 20.117(4), b = 23.449(5), c = 7.852(2) ?, V = 3703.9(12) ?³, Z = 24 (three independent molecules per asymmetric unit), density (calculated) = 1.584 mg/m³, absorption coefficient 0.755 mm⁻¹. For I in the final refinement cycle the data/restraints /parameter ratios were 2639/0/161, goodness-of-fit on F² = 0.934, final R indices [I > 2sigma(I)] were R1 = 0.0299, wR2 = 0.0545 and R indices (all data) R1 = 0.0399, wR2 = 0.0568. The largest difference peak and hole were 0.402 and −0.259 e ?⁻³. For II in the final refinement cycle the data/restraints/parameter ratios were 3372/1/221, goodness-of-fit on F² = 0.950, final R indices [I > 2sigma(I)] were R1 = 0.0407, wR2 = 0.1048 and R indices (all data) R1 = 0.0450, wR2 = 0.1088. The absolute structure parameter = 0.19(9) and largest difference peak and hole 0.934 and −0.301 e ?⁻³. Details of the geometry of the five molecules (two for I and three for II) and the crystal structures are fully discussed. Corresponding features of the molecular geometry are highly consistent and firmly establish the geometry of the rhodanine ring. Index Abstract  Low temperature X-ray structures of (I) 3-aminorhodanine [3-amino-2-thio-4-oxothiazolidine] and (II) 3-methylrhodanine3-methyl-2-thio-4-oxothiazolidine are presented. Crystals of I are monoclinic and occupy space group P2₁/n with eight molecules (2 per asymmetric unit cell) and (II) is orthorhombic in space group Iba2 with 24 molecules (3 per asymmetric unit). This study has provided five highly consistent copies of the rhodanine ring at high resolution thus enabling its geometry to be established with confidence. The two independent molecules in the asymmetric unit of 3-aminorhodanine (left) and the three independent molecules in the asymmetric unit of 3-methylrhodanine (right) showing space filling and van der Waals contacts (drawn with MERCURY [Bruno et al. Acta Cryst B58:389, 2002]).     

Synthesis and Structural Characterization of Two New Layered Inorganic–Organic Hybrid Zinc Phosphites Templated by Cyclam: Zn(HPO3)2·0.5(C10H28N4) and Zn2(HPO3)3·0.5(C10H28N4)

Abstract  

Using 1,4,8,11-tetraazacyclotetradecane (cyclam) as a template, two new layered zincophosphites, Zn(HPO₃)₂·0.5(C₁₀H₂₈N₄) (1) and Zn₂(HPO₃)₃·0.5(C₁₀H₂₈N₄) (2), were synthesized and characterized by single crystal X-ray diffraction. The two new compounds crystallize in the triclinic system with the space group P − 1 and the cell parameters: a = 8.3130 ?, b = 8.7289 ?, c = 9.0055 ?, α = 106.90(1), β = 95.56(1), γ = 105.30(1), V = 592.31 ?³, Z = 2 for 1 and a = 9.0406 ?, b = 9.4234 ?, c = 9.4519 ?, α = 91.19(1), β = 100.73(1), γ = 106.85(1), V = 754.82 ?³, Z = 2 for 2. Both structures are described in terms of phosphometallic slabs hosting the cyclam cation.     

Kinetics of Desolvation and Structure of Bulky Xanthenol Inclusion Compounds

Abstract  The inclusion compounds of 14-hydroxy-14-toluenyldibenzo[a:j]xanthene (H) with the guests acetone (H·ACE), pyridine (H·PYR) and N,N-dimethylformamide (H·DMF) were all successfully solved in the triclinic spacegroup P-1 with unit cell dimensions for H·ACE: a = 9.415(2) ?, b = 9.730(2) ?, c = 12.994(3) ?, α = 82.65(3), β = 76.69(3), γ = 88.67(3), Z = 2; for H·PYR: a = 9.482(2) ?, b = 10.169(2) ?, c = 13.089(3) ?, α = 106.59(3), β = 95.91(3), γ = 90.35(3), Z = 2 and for H·DMF: a = 9.537(19) ?, b = 10.055(2) ?, c = 13.129(3) ?, α = 79.18(3), β = 74.42(3), γ = 86.46(3), Z = 2. The thermal stabilities for all compounds were investigated and in particular the kinetics of desolvation for the DMF compound was determined using both isothermal and non-isothermal methods. Index Abstract  The host compound 14-hydroxy-14-toluenyldibenzo[a:j]xanthene forms inclusion compounds with the guests acetone, pyridine and N,N-dimethylformamide. The crystal structures were determined and their thermal stabilities investigated. The kinetics of desolvation for the DMF compound was determined using both isothermal and non-isothermal methods.      

Synthesis,Characterization and Crystal Structure of Bis(isothiocyanato)-bis(pyridine) Zinc(II) Crystal

Abstract  Bis(isothiocyanato)-bis(pyridine) zinc(II) crystal has been prepared at room temperature and characterized by elemental analysis, IR spectrum and X-ray single crystal determination. The complex crystallizes in monoclinic space group P2₁/m with unit cell parameters: a = 5.5786(3), b = 11.0587(5), c = 12.1616(6) ?, β = 96.776(3)°, V = 745.03(6) ?³, Z = 2, D _x  = 1.514 g cm⁻³. The X-ray structure determination has revealed that the crystal is centered-symmetrical and the crystallographic symmetry face runs the two isothiocyanate ligands and the Zn(II) cation. Index Abstract  The title compound, bis(isothiocyanato)-bis(pyridine) zinc(II), was synthesized by zinc compound, KSCN and C₅H₅N (pyridine) and its crystal structure was determined. Single crystal X-ray structure determination reveals that the crystal is centered-symmetrical, and the crystallographic symmetry face runs the two isothiocyanate ligands and the Zn(II) cation.      

Synthesis and Crystal Structure Analysis of Substituted Diethyl Malonate

Abstract  

As intermediates of light stabilizer malonate, diethyl 3,5-di-t-butyl-4-hydroxybenzyl phenyl malonates (F.W. 454.58) was synthesized, characterized by ¹H NMR, element analysis and confirmed by X-ray crystal structure analysis. This compound crystallizes in monoclinic class under the space group P21/c with cell parameters, a = 9.8218(4) ?, b = 13.5571(5) ?, c = 19.7233(8) ?; β = 102.3530(10)°, and Z = 4. The structure exhibits inter-molecular hydrogen bonds of the type O–H–O, leading to the formation of one dimensional chains.