Synthesis of methyl epijasmonate and cis-3-(2-oxopropyl)-2-(pent-2Z-enyl)-cyclopentan-1-one

A novel and efficient synthesis of both (±)-methyl epijasmonate and (±)-cis-3-(2-oxopropyl)-2-(pent-2Z-enyl)-cyclopentan-1-one is described. The key step to establish the cis-stereochemistry on the 5-membered ring is an ionic Diels–Alder reaction, which is high yielding and highly regioselective. Subsequent key steps include oxidative cleavage of the six-membered ring, Wittig coupling and for the synthesis of epijasmonate, the haloform reaction.     

Lipase TL®-mediated kinetic resolution of benzoin: facile synthesis of (1R,2S)-erythro-2-amino-1,2-diphenylethanol

The lipase TL®-mediated kinetic resolution of (±)-benzoin (1) proceeded to give the corresponding optically pure benzoin (R)-1. On the other hand, (S)-benzoin-O-acetate (5) could be hydrolyzed without epimerization to give (S)-benzoin (S)-1, under alkaline conditions. Further, (R)-1 was converted to (1R,2S)-2-amino-1,2-diphenylethanol (99:1 er) according to the procedure reported previously.     

Structural and spectral studies of N-2-(pyridyl)-, N-2-(3-, 4-, 5-, and 6-picolyl)- and N-2-(4,6-lutidyl)-N′-2-thiomethoxyphenylthioureas

Structures of the following compounds have been obtained: N-(2-pyridyl)-N′-2-thiomethoxyphenylthiourea, PyTu2SMe, monoclinic, P2₁/c, a=11.905(3), b=4.7660(8), c=23,532(6) Å, β=95.993(8)°, V=1327.9(5) ų and Z=4; N-2-(3-picolyl)-N′-2-thiomethoxyphenyl-thiourea, 3PicTu2SeMe, monoclinic, C2/c, a=22.870(5), b=7.564(1), c=16.941(4) Å, β=98.300(6)°, V=2899.9(9) ų and Z=8; N-2-(4-picolyl)-N′-2-thiomethoxyphenylthiourea, 4PicTu2SMe, monoclinic P2₁/a, a=9.44(5), b=18.18(7), c=8.376(12) Å, β=91.62(5)°, V=1437(1) ų and Z=4; N-2-(5-picolyl)-N′-2-thiomethoxyphenylthiourea, 5PicTu2SMe, monoclinic, C2/c, a=21.807(2), b=7.5940(9), c=17.500(2) Å, β=93.267(6)°, V=2893.3(5) ų and Z=8; N-2-(6-picolyl)-N′-2-thiomethoxyphenylthiourea, 6PicTu2SMe, monoclinic, P2₁/c, a=8.499(4), b=7.819(2), c=22.291(8) Å, β=90.73(3)°, V=1481.2(9) ų and Z=4 and N-2-(4,6-lutidyl)-N′-2-thiomethoxyphenyl-thiourea, 4,6LutTu2SMe, monoclinic, P2₁/c, a=11.621(1), b=9.324(1), c=14.604(1) Å, β=96.378(4)°, V=1572.4(2) ų and Z=4. Comparisons with other N-2-pyridyl-N′-arylthioureas having substituents in the 2-position of the aryl ring are included.     

Structural, spectral and thermal studies of N-2-(4-picolyl)- and N-2-(6-picolyl)-N′-(2-chlorophenyl)thioureas and N-2-(6-picolyl)-N′-(2-bromophenyl)thiourea

N-2-(4-picolyl)-N′-2-chlorophenylthiourea, 4PicTu2Cl, monoclinic, P2₁/c, a=10.068(5), b=11.715(2), β=96.88(4)°, and Z=4; N-2-(6-picolyl)-N′-2-chlorophenylthiourea, 6PicTu2Cl, triclinic, P-1, a=7.4250(8), b=7.5690(16), c=12.664(3) Å, =105.706(17), β=103.181(13), γ=90.063(13)°, V=665.6(2) ų and Z=2 and N-2-(6-picolyl)-N′-2-bromophenylthiourea, 6PicTu2Br, triclinic, P-1, a=7.512(4), b=7.535(6), c=12.575(4) Å, a=103.14(3), β=105.67(3), γ=90.28(4)°, V=665.7(2) ų and Z=2. The intramolecular hydrogen bonding between N′H and the pyridine nitrogen and intermolecular hydrogen bonding involving the thione sulfur and the NH hydrogen, as well as the planarity of the molecules, are affected by the position of the methyl substituent on the pyridine ring. The enthalpies of fusion and melting points of these thioureas are also affected. ¹H NMR studies in CDCl₃ show the NH′ hydrogen resonance considerably downfield from other resonances in their spectra.     

Synthesis and X-ray crystal structures of rac- and meso-2,2′-propylidene-bis(1-indenyl) zirconium dichlorides

An improved synthesis of 2,2′-bis(1-indenyl)propane and the corresponding ansa-complexes of zirconium are reported. Synthesis of a mixture of rac- and meso-2,2′-propylidene-bis(1-indenyl)zirconium dichlorides involves a treatment of ZrCl₄ with bis[3-(trialkyltin)inden-1-yl]propane, where alkyl = ethyl, butyl, in toluene. This reaction gives the products in 92% yield and might be a convenient synthetic pathway to a number of straightforward ansa-metallocenes. Both rac- and meso-2,2′-propylidene-bis(1-indenyl)zirconium dichlorides were separated and isolated using simple work-up processes, and characterized by X-ray crystal structure analysis (rac:C2/c; a = 15.903(3) Å, b = 11.105(2) Å and c = 11.520(2) Å; β = 121.61(3)°; Z = 4; V = 1732.6(5) ų; R = 0.0350; meso-: P1¯; a = 9.739(2) Å, b = 12.798(4) Å and c = 15.322(4) Å; = 101.18(2)°; β = 121.61(2)°; γ = 90.54(2)°, Z = 4; V = 1795.4(8) ų; R = 0.0417).     

Enzymatic production of (3S,4R)-(−)-4-(4′-fluorophenyl)-6-oxo-piperidin-3-carboxylic acid using a commercial preparation from Candida antarctica A: the role of a contaminant esterase

The enantioselective hydrolysis of (3RS,4RS)-trans-4-(4′-fluorophenyl)-6-oxo-piperidin-3-ethyl carboxylate (±)-2 was effected using a commercial preparation of lipase from C. antarctica A (CAL-A). We found that the hydrolytic activity of the lipase (immobilized on a number of very different supports) with this substrate was negligible. However, a contaminant esterase with Mw of 52 KDa from this commercial preparation exhibited much higher activity with (±)-2. This enzyme was purified and immobilized on PEI-coated support and the resulting enzyme preparation was highly enantioselective in the hydrolysis of (±)-2 (E >100), hydrolyzing only the (3S,4R)-(−)-3, which is a useful intermediate for the synthesis of pharmaceutically important (−)-paroxetine. Optimization of the reaction system was performed using a racemic mixture with a substrate concentration of 50 mM. This enzyme preparation was used in three reaction cycles and maintained its catalytic properties.     

Conformational and structural analysis of N-N′-bis(4-methoxybenzylidene)ethylenediamine

The Schiff base compound, N-N′-bis(4-methoxybenzylidene)ethylenediamine (C₁₈H₂₀N₂O₂) has been synthesized and its crystal structure has been investigated by X-ray analysis and PM3 method. The compound crystallizes in monoclinic space group P2₁/n with a=10.190(1), b=7.954(1), c=10.636(1) Å, β=111.68(1)°, V=801.1(1) ų, Z=2 and D_cal=1.229 Mgm⁻³. The title structure was solved by direct methods and refined to R=0.056 for 2414 reflections [I>3.0σ(I)] by full-matrix anisotropic least-squares methods. The energy profile of the compound was calculated by PM3 method as a function of θ[N1′–C9′–C9–N1]. The most stable molecular structure of the title compound is the anti conformation, which is different in energy by 5.0 and 1.0 kcal mol⁻¹ from the eclipsed conformation I and gauche conformations, (III and V), respectively.     

Kinetic study of gas-phase Lu(D3/2) with O2, N2O and CO2

The second-order rate constants of gas-phase Lu(²D_3/2) with O₂, N₂O and CO₂ from 348 to 573 K are reported. In all cases, the reactions are relatively fast with small barriers. The disappearance rates are independent of total pressure indicating bimolecular abstraction processes. The bimolecular rate constants (in molecule⁻¹ cm³ s⁻¹) are described in Arrhenius form by k(O₂)=(2.3±0.4)×10⁻¹⁰exp(−3.1±0.7 kJmol⁻¹/RT), k(N₂O)=(2.2±0.4)×10⁻¹⁰exp(−7.1±0.8 kJmol⁻¹/RT), k(CO₂)=(2.0±0.6)×10⁻¹⁰exp(−7.6±1.3 kJmol⁻¹/RT), where the uncertainties are ±2σ.     

Stereoselective synthesis of (1R,2S)-2-amino-1,3-diols from (R)-cyanohydrins

Vinyl substituted (1R,2S)-amino alcohols 5 were obtained by addition of vinyl magnesium bromide to the corresponding cyanohydrin O-trimethylsilyl ethers (R)-2. The O- and N-protected vinyl amino alcohols 6 were ozonized at −78°C in methanol yielding (1R,2S)-2-amino-1,3-diols7 in high enantiomeric and diastereomeric excesses. For purification, compounds 7 in some cases were acetylated to give the derivatives (1R,2S)-8. Racemic 6a was converted by oxidative ozonolysis at −78°C in methanolic NaOH solution to the corresponding methyl N-acetyl-β-hydroxy propanoate 9a. The configuration of (1R,2S)-8a was confirmed by x-ray crystallographic analysis.     

Nido-6-metalladecaborane chemistry: Molecular structure and fluxionality of [6,6,6,6-(CO)2(PPh3)2-nido-6-WB9H13]

The molecular and crystal structure of the nido-6-tungstadecaborane [6,6,6,6-(CO)₂(PPh₃)₂-nido-6-WB₉H₁₃] (1) has been determined showing that the tungsten atom is incorporated into the 6-position of a nido 10-vertex (WB₉) cage. The tungsten atom has a seven-coordinate capped trigonal prismatic environment and is bonded to two hydrogen and three boron atoms of the {B₉H₁₃} cage, in addition to two CO groups and two PPh₃ ligands. Variable-temperature (−90°C to +50°C) ³¹P{¹H} NMR spectroscopy of 1 reveals that the exo-polyhedral ligands about the tungsten atom are fluxional with respect to PPh₃ site exchange with an activation energy (ΔG‡), at the coalescence temperature (−73°C), of <38 kJ mol⁻¹.     

Structural and spectral studies on N-(4-chloro)benzoyl-N′-(4-tolyl)thiourea

The crystal and molecular structure of the N-(4-chloro)benzoyl-N′-(4-tolyl)thiourea (C₁₅H₁₃N₂OSCl, M_r=304.79) is determined by X-ray diffraction. The crystal structure is monoclinic, space group: P2₁/n, a=16.097(6), b=4.5989(2), c=19.388(7) Å and β=89.299(6)° V=1434.7(9)ų, Z=4. FTIR and NMR spectra have been characterized. The interactions of intramolecular and intermolecular hydrogen bonds have been discussed. Density functional theory (DFT) (B3LYP) methods have been used to determine the structure and energies of stable conformers. Minimum energy conformations are calculated as a function of the torsion angle θ (C13–N1–C14–N2) varied every 30°. The optimized geometry corresponding to crystal structure is the most stable conformation. This has partly been attributed to intramolecular hydrogen bonds. With the basis sets of the 6-311G* quality, the DFT calculated bond parameters and harmonic vibrations are predicted in a very good agreement with experimental data.     

Tautomeric properties, conformations and structure of N-(2-hydroxy-5-chlorophenyl) salicylaldimine

The crystal structure of N-(2-hydroxy-5-chlorophenyl) salicylaldimine (C₁₃H₁₀NO₂Cl) was determined by X-ray analysis. It crystallizes orthorhombic space group P2₁2₁2₁ with a=12.967(2) Å, b=14.438(3) Å, c=6.231(3) Å, V=1166.5(6) Å³, Z=4, D_c=1.41 g cm⁻³ and μ(MoK)=0.315 mm⁻¹. The title compound is thermochromic and the molecule is nearly planar. Both tautomeric forms (keto and enol forms in 68(3) and 32(3)%, respectively) are present in the solid state. The molecules contain strong intramolecular hydrogen bonds, N1–H1O1/O2 (2.515(1) and 2.581(2) Å) for the keto form and O1–H01N1 for the enol one. There is also strong intermolecular O2–HO1 hydrogen bonding (2.599(2) Å) between neighbouring molecules. Minimum energy conformations AM1 were calculated as a function of the three torsion angles, θ₁(N1–C7–C6–C5), θ₂(C8–N1–C7–C6) and θ₃(C9–C8–N1–C7), varied every 10°. Although the molecule is nearly planar, the AM1 optimized geometry of the title compound is not planar. The non-planar conformation of the title compound corresponding to the optimized X-ray structure is the most stable conformation in all calculations.     

Synthesis and Crystal Structure of 5-N-i-Propyl-2- （ 2＇ -nitrobenzenesulfonyl） -glutamine

The title compound, 5-N-i-propyl-2-(2′-nitrobenzenesulfonyl)-glutamine, was synthesized and its structure was confirmed by IR, MS, ¹H NMR, and elemental analysis. The single crystal structure of the title compound was determined by X-ray diffraction. The crystal belongs to Monoclinic, space group P2 (1), with a = 0.69281(11) nm, b = 0.76508(12), c = 1.5843(3) nm, = 90°, β = 90.941(3)°, γ = 90°, V = 0.8397(2) nm³, Z = 2, D_c = 1.477 g/cm³, μ = 0.236 mm^-1, F(000) = 392, R = 0.0297, and wR = 0.0664.     

Determination of compositions and isomer structures in mixtures of cis- and trans-1,2-dichloroethene (ClHC=CHCl) by gas-phase electron diffraction

Using gas-phase electron diffraction it has been demonstrated that a composition of known isomer mixtures can be determined with error limits of about 5%, all relevant structural parameters being refined simultaneously by the least-squares method. If, however, corresponding bond distances and valence angles have erroneously been assigned equal values in the two isomers, a large increase in the least-squares error limits from 5% to 12% is noticed. Apparently innocent assumptions about some of the parameters can lead to incorrect isomer composition and to too small error limits as estimated by the least-squares formulae.

From the reinvestigation of pure cis-1,2-dichloroethene the following bond distances (r_a) and valence angles () were determined: r(C---H) = 1.090(29) Å, r(C=C) = 1.345(6) Å, r(C---Cl) = 1.716(4) Å, C=C---Cl = 123.8(2)°, C=C---H = 119.4(26)°. Error limits are 2σ.     

Influence of DFT-calculated electron correlation on energies and geometries of retinals and of retinal derivatives related to the bacteriorhodopsin and rhodopsin chromophores

DFT-calculations were performed on retinal in the all-trans, 1, 11-cis-12-s-cis, 2, and 11-cis-12-s-trans configuration, 3, and on the corresponding N-methyl Schiff base and protonated N-methyl Schiff base derivatives; for the latter, the corresponding 6-s-trans conformations and the 6-s-trans-13-cis-14-s-trans isomer which play a role in the bacteriorhodopsin photocycle were also studied. All geometries were fully optimized using the Becke- three-parameter Lee-Yang-Parr method in conjunction with the 6-31G^** basis set (B3LYP/6-31G^**). The stabilities in order of increasing energy are 1, 3 and 2 regardless of the type of substitution of the end group. While the energy of 3 relative to 1 is almost constant (5 ± 0.2 kcal mol⁻¹), the relative energy of 2 depends somewhat on the nature of the functional group: it is highest in the protonated Schiff base derivative 2-SBH + with its steric congestion along the C12-C13 bond. Comparison with results previously obtained on the basis of RHF/6-31G^** ab initio calculations reveals that the B3LYP method is more biased towards π-electron delocalization. This is indicated by the reduced degree of double bond fixation along the chromophore and also in the increased tendency towards planarization as manifest, e.g. by the change of the C5-C6-C7-C8 dihedral angle between the cyclohexene ring and the open chain double bond system.     

Enzymatic desymmetrization of meso cis,cis-2,4,6-substituted tetrahydropyrans

The stereoselective acylation of meso-tetrahydropyrans 6 and 7 by enol esters (vinyl acetate or isopropenyl acetate) in the presence of Candida antarctica lipase in organic media gave the corresponding (2R,4S,6S)-monoesters 10 and 11 in high enantiomeric purity. The hydrolysis of the corresponding diacetate derivatives 8 and 9 in the presence of the same enzyme provided the opposite enantiomers, (2S,4R,6R)-monoesters 10 and 11.     

Convenient diastereospecific synthesis of a rociverine precursor and its resolution by lipase-catalyzed transesterification

(±)-1-Cyclohexyl-c-2-hydroxymethyl-r-1-cyclohexanol 3, a precursor of the antimuscarinic drug Rociverine 1, was obtained diastereospecifically in very high yield, from the Grignard reaction between C₆H₁₁MgCl and an appropriately protected 2-(hydroxymethyl)cyclohexanone. The preparation of enantiomerically enriched cis diol (+)-(1R,2S)-3 and the corresponding 2-acetoxymethyl derivative (+)-(1S,2R)-12 was achieved by lipase PPL-catalyzed transesterification of racemic diol (±)-3.     

Preparation and structure of a ruthenium dicarbonyl derivative of the P2N4S2 ring

The reaction of Ru(CO)₄(C₂H₄) or Ru(CO)₅ with 1,5-Ph₄P₂N₄S₂ in CH₂Cl₂/hexane at 23°C produces the dimer [Ru(CO)₂(Ph₄ P₂N₄S₂)]₂ (2), which was shown by X-ray crystallography to have a centrosymmetric structure in which the P₂N₄S₂ ring is attached to one ruthenium atom through two (geminal) nitrogen atoms and the remote sulfur atom and serves as a bridge to the other ruthenium atom via the second sulfur atom. Crystals of 2 ·2(CH₂Cl₂) are triclinic, space group P (No. 2), a = 12.901(1) Å, b = 13.072(1) Å, c = 10.123(1) Å, = 100.88(1)°, β = 98.90(1)°, γ = 67.50(1)°, V = 1542.4(3) Å, Z = 1 with final R and R_w values of 0.040 and 0.027, respectively.     

Lipase-catalyzed kinetic resolution of cis-1-diethylphosphonomethyl-2-hydroxymethylcyclohexane. Application to enantioselective synthesis of 1-diethylphosphonomethyl-2-(5′-hydantoinyl)cyclohexane

A kinetic resolution of cis-1-diethylphosphonomethyl-2-hydroxymethylcyclohexane1 by lipase has been developed. The transesterification of (±)−1 with vinyl acetate in the presence of Lipase AK without solvent proceeded to give (+)−1 and the corresponding acetate (+)−5 in good yield and high enantiomeric ratio. The alcohol (+)−1 was transformed to the optically active hydantoins 12 and 13, possible intermediates for the synthesis of conformational constrained analogues of AP-5.     

Hydrothermal syntheses and crystal structures of bimetallic cluster complexes [{Cd(phen)2}2V4O12]·5H2O and [Ni(phen)3]2[V4O12]·17.5H2O

The hydrothermal reactions of vanadium oxide starting materials with divalent transition metal cations in the presence of nitrogen donor chelating ligands yield the bimetallic cluster complexes with the formulae [{Cd(phen₂)₂V₄O₁₂]·5H₂O (1) and [Ni(phen)₃]₂[V₄O₁₂]·17.5H₂O (2). Crystal data: C₄₈H₅₂Cd₂N₈O₂₂V₄ (1), triclinic. a=10.3366(10), b=11.320(3), c=13.268(3) Å, =103.888(17)°, β=92.256(15)°, γ=107.444(14)°, Z=1; C₇₂H₁₃₁N₁₂Ni₂O_29.5V₄ (2), triclinic. a=12.305(3), b=13.172(6), c=15.133(4), =79.05(3)°, β=76.09(2)°, γ=74.66(3)°, Z=1. Data were collected on a Siemens P4 four-circle diffractometer at 293 K in the range 1.59° <θ<26.02° and 2.01°<θ<25.01° using the ω-scan technique, respectively. The structure of 1 consists of a [V₄O₁₂]⁴⁻ cluster covalently attached to two {Cd(phen)₂}²⁺ fragments, in which the [V₄O₁₂]⁴⁻ cluster adopts a chair-like configuration. In the structure of 2, the [V₄O₁₂]⁴⁻ cluster is isolated. And the complex formed a layer structure via hydrogen bonds between the [V₄O₁₂]⁴⁻ unit and crystallization water molecules.