Drake S. Eggleston

An efficient asymmetric synthesis of substituted phenyl glycidic esters

Abstract Chiral substituted glycidic esters have been prepared from their corresponding chalcones via a two step procedure consisting of an asymmetric epoxidation mediated by a poly-L-leucine polymer, followed by a previously unreported Baeyer-Villiger oxidation. The regioselectivity of this latter procedure was found to depend on the aryl substituent.

Metal-drug interactions: synthesis and crystal structure of dichlorodithiabendazolecobalt(II) monohydrate

Abstract The crystal structure of dichlorodithiabendazolecobalt(II) monohydrate [CoCl2(C10H7N3S)2·H2O] has been determined from X-ray diffraction data using Mo Kα radiation. The crystals are monoclinic, P2 1 /c with a = 15.328(5), b = 11.2131(8), c = 13.967(5) A , β = 114.27(1)° and Z = 4 . The structure was solved and refined to a final R value of 0.0332 with 3717 observed reflections. Two chlorine atoms and two thiabendazole ligands form an octahedral geometry around cobalt. Each thiabendazole, [2-(4-thiazolyl)-1H-benzimidazole], is bidendate chelating and is bonded to cobalt through the nitrogen atoms of the thiazolyl and benzimidazole rings in cis configuration. The protonated nitrogen atom of the imidazole ring is trans to the thiazole nitrogen atom.

Structure and magnetism in the chloro-bridged copper(II) complex Di-μ-chloro-bis[chlorobis(4-methyloxazole)copper(II)

Abstract The dimeric complex bis[dichlorobis(4-methyloxazole)copper(II)], [Cu(4-Meox) 2 Cl 2 ] 2 or [CuC 4 H 5 NO) 2 Cl 2 ] 2 has been synthesized and its structure has been determined from three-dimensional counter X-ray data. The complex crystallizes in the monoclinic space group P2 1 /n with two dimeric formula units in a cell of dimensions a= 8.177(2), b = 12.866(5), c = 11.063(6) A,β = 98.31(3)°. The structure has been refined by least-squares techniques to a value of the conventional R-factor (on F) of 0.033 based on 2071 independent data. The geometry at each copper center is severely distorted tetragonal pyramidal, the basal ligands being two trans nitrogen atoms from the 4-Meox ligands and two trans chloride ligands while the apical site is occupied by an inversion-related chloride ion. Thus, the dimeric entity is of the axial-equatorial type in which the inversion-related bridging chloride ligands are each axial to one copper and equatorial to the other. The Cuue5f8Cu separation in the dimer is 3.507(1) A and the bridging Cuue5f8Clue5f8Cu′ angle (φ) is 89.46(2)°. The magnetic susceptibility of the complex exhibits a maximum near 2 K, and the data have been fitted to the magnetization expression yielding g = 2.118 and a singlet-triplet separation of 2.6 cm −1 with the singlet as the ground state.

Histidyl conformations and short N–H⋯N hydrogen bonds: Structure of d,l-histidyl-l,d-histidine pentahydrate

D,L-Histidyl-L,D-histidine pentahydrate, C12H16-N6O3.5H2O, Mr = 382.38, F(000) = 408, crystallizes in the monoclinic space group Pc with the cell dimensions a = 9.971 (2), b = 4.745 (2), c = 19.572 (3) A and beta = 96.08 (1) degree, V = 920.6 A3, Z = 2, D chi = 1.379 g cm-3. mu = 1.083 cm-1, T = 295 K, Mo K alpha, lambda = 0.71073 A. Final R (on F) = 0.040 for 1658 observed reflections with I greater than or equal to 3 sigma (I). This dipeptide crystallizes in a zwitterionic form with protonation of the C-terminal imidazole ring. Both histidine units exist in the g+ or closed conformation with C alpha-C beta torsion angles of 67.2 (3) and 63.6 (3) degrees. Principal torsion angles, omega = 176.8 (2). psi 1 = 161.8 (3) and phi 2 = -152.1 (3) degrees, are indicative of a highly extended trans conformation. Intramolecular hydrogen bonding occurs between the imidazole rings [N2D-H2D1...N1D = 2.724 (4) A]. Intermolecular hydrogen bonding occurs between symmetry-related histidine molecules forming chains along the gamma axis and includes another short [2.764 (4) A] N-H...N interaction. The five water molecules occupy channels between adjacent histidine layers.

Hydro­gen bonding patterns in trimethoprim sulfate trihydrate [trimethoprim = 2,4-di­amino-5-(3,4,5-methoxy­benzyl)­pyrimidine]

Trimethoprim sulfate trihydrate, 2C14H19N4O3+·SO42−·3H2O [(TMPH+)2(SO4)2−·3H2O, TMPH+ = 2,4-dixadamino-5-(3,4,5-methoxyxadbenzyl)xadpyrimidin-1-ium], is an antibacterial agent. In its N1-protonated form, it inhibits the bacterial dixadhydroxadfolate reductase enzyme. The asymmetric unit contains two TMPH cations, a sulfate anion and three water molxadecules. The TMPH cations are each paired about their respective inversion centres via N—H⋯N hydrogen bonds. These pairs are further bridged by a network of hydrogen bonds involving the sulfate anion and water molxadecules. Both the TMPH cations make hydrogen bonds with water molxadecules through the 2-amino groups, reminiscent of TMP-dixadhydroxadfolate reductase complexes. The pyrimidine plane makes a dihedral angle of 75.89u2005(8)° with the phenyl ring in one TMPH cation, the corresponding angle in the other moiety being 69.96u2005(8)°.

Molecular structures of l-Leu-l-Tyr, Gly-d,l-Met.p-toluenesulfonate and l-His-l-Leu

L-Leu-L-Tyr, (I), C15H22N2O4, M(r) = 294.35, crystallizes from MeOH/5% dimethyl sulfoxide in the orthorhombic space group P2(1)2(1)2(1). a = 5.644 (1), b = 12.094 (3), c = 22.548 (4) A, V = 1539.0 (5) A3, Z = 4, Dx = 1.270 g cm-3, Cu K alpha, lambda = 1.54184 A, mu = 7.228 cm-1, F(000) = 632, T = 173 K, final R (on F) = 0.033 for 1347 observations with I > or = 2 sigma (I). (I) crystallizes as a zwitterion with the N-terminus protonated and the C-terminus ionized. The peptide backbone adopts a distorted trans antiparallel beta pleated-sheet conformation, with principal torsion angles psi 1 = 163.7 (2), omega 1 = 158.7 (2), phi 2 = -110.9 (3) and psi 2 = 141.4 (2)degrees. The leucyl residue is in the g-(tg-) conformation while the tyrosyl residue adopts the g- conformation, with the phenol ring twisted from the low-energy perpendicular position. Gly-D,L-Met.p-toluenesulfonate, (II), C7H15N2O3S+.C7H7O3S-, M(r) = 378.47, crystallizes from MeOH/EtOAc in the orthorhombic space group Pbca. a = 33.642 (4), b = 15.951 (1), c = 6.785 (1) A, V = 3641.0 (4) A3, Z = 8, Dx = 1.381 g cm-3, Cu K alpha, lambda = 1.54184 A, mu = 28.865 cm-1, F(000) = 1600, T = 223 K, final R (on F) = 0.055 for 1669 observations with I > or = 3 sigma (I). Gly-D,L-Met exists as a cation with the N- and C-termini protonated, the p-toluenesulfonate being the counterion.(ABSTRACT TRUNCATED AT 250 WORDS)

Open-cyclic warfarin isomerism: 5-hydroxywarfarin

Addition of a 5-hydroxy substituent to warfarin [3-(1-phenyl-3-oxobutyl)-4-hydroxycoumarin] shifts the solution equilibrium in chloroform to favor the open isomeric form over the two cyclic diastereomeric hemiketals. X-ray diffraction analysis reveals 5-hydroxywarfarin crystallizes as the open isomer in contrast to the more than 20 warfarin and analog structures which occur ascis ortrans hemiketal forms in the solid. The two peri hydroxyl groups in the structure of 3-(1-phenyl-3-oxobutyl)-4,5-dihydroxycoumarin are intramolecularly H-bonded. Methyl kctal derivatives of 5-hydroxywarfarin and a close analog effectively model the minor cyclic hemiketal forms in solution. Structures of bothcis andtrans cyclic methyl ketals of 3-(4-oxopent-2-yl)-4,5-dihydroxy-coumarin have been determined and the aryl hydroxyls H-bond to the dihydropyranyl ring oxygens of the cyclic ketals. Nuclear magnetic resonance studies suggest that these intramolecular H-bonds persist in chloroform solution. Infrared spectroscopy on the series of compounds in KBr pellets is consistent with the crystallographically determined structures and H-bonding schemes.

Structural Variations in 3,4-Dihydro-2H-pyran Ketals: Acyl and Aryl Warfarin Derivatives

The crystal structures of (_)-cis-2-methyl-5-oxo-4phenyl-3,4-dihydro-2H,5H-pyrano[3,2-c][1]benzopyran-2-yl acetate [C21H1805, Mr = 35037, monoclinic, P2Jn, a = 12.091 (4), b = 8.288 (3), c = 17.840 (5)A, fl=106.34(2) ° , V=1715(2) A 3, Z=4, Dx= 1.356 g cm -3, A(Mo K~) = 0.7107 A, /z = 0.904 cm-~, F(000) = 736, T = 295 K, R = 0.050 for 2767 observations with I>_ 3tr(/)] and (6R,12S)-(-)6,8-dimethyl-6,12-methano-6H, 12H, 13H-[1]benzopyran[4,3-d][1,3]benzodioxocin-13-0ne [C20Hi604, Mr = 320.36, tetragonal, P43, a = 10.788 (4), c = 13.587 (9) A, V= 1581 (2) A 3, Z = 4, Ox = 1.345 g cm -3, a(Mo K~) = 0.7107 ,~, /z = 0.873 cm-l, F(000) = 672, T = 295 K, R = 0.049 for 1425 observations with I___ 2-5tr(/)] are described. They are acyl and aryl ketals of warfarin, respectively, and contain an embedded dihydropyran ring. The molecules were studied as part of a series of axial 2-O-substituted-2-methyl-3,4-dihydro-2Hpyran structures which show (hemi)ketal C---O bond-length variations indentified through factor analysis with the systematic geometrical changes associated with a spontaneous elimination (El-like) reaction from the ketal leading to 2-methyl-4Hpyran. As in a-tetrahydropyranyl acetals, the C--O lengths in dihydropyranyl ketals can be expressed as a function of the electron-withdrawing ability of the substituent conjugate base, and the slopes of the relationships for the two systems are similar. Corresponding endocyclic C--O lengths are about 0.052 A longer in these model dihydropyranyl ketals.

Diastereomeric Discrimination: Structural Aspects

Study of crystal and molecular structures offers detailed pictures of intermolecular interactions in the solid state. These serve as exemplars for the understanding of intermolecular interactions in the disordered phases of the liquid state and solution. Properties and reactivity of chemical species and systems are axiomatically related to their structure. One of the most important and active areas of structural study concerns molecular complexation. The concept of structural complementarity underlies a wide range of chemical and biological topics embracing antigen-antibody interactions, enzyme-substrate and enzyme-inhibitor interactions, and host-guest relationships, many with potential and application among the separation sciences. One of the oldest of the physical separation methods with a history of practical exploitation is the use of diastereomeric complexes for (partial) resolution of enantiomeric mixtures (Pasteur, 1853). The traditional method takes advantage of the differential solubility of the complexes in an appropriately chosen solvent. Since the less-soluble phase separates from solution usually as a crystalline solid leaving the more-soluble phase in solution, the less-soluble phase is a molecular assembly with macroscopic properties palpably different from its diastereomeric relative. And so it is not surprising that together with the lower solubilities, one finds higher heats of solution, heats of fusion and fusion points for the less-soluble phases (Jacques, Collet & Wilen, 1981).

Structures of cis-4-(2'-methoxyphenyl)- (1) and trans-4-(3'-methoxy-4'-hydroxyphenyl)-2-hydroxy-2-methyl-3,4-dihydro-2H,5H-pyrano[3,2-c][1]benzopyran-5-one (2)

Cristallisation dans P1 avec affinement jusque 0,054 pour le premier compose. Cristallisation dans P2 1 /n avec affinement jusqua 0,0415 pour le second compose