Mannich Base Derivatives of 1,2-Benzisothiazolin-3-one: Syntheses, Crystal Structures and Bioactivities

Twelve Mannich base derivatives of 1,2-benzisothiazolin-3-one were synthesized by the reaction of 1,2-benzisothiazol-3（2H）-one （BIT） with different amines and formaldehyde. All the compounds were characterized by elemental analysis, IR spectroscopy, MS and 1H NMR. The crystal structure for 2,2＇-methylenebis（benzo[d]isothiazol-3（2H）-one） （3） has been determined by X-ray single-crystal structure analysis. Compound 3 （C15HIoN202S2） crystallizes in the monoclinic system, space group C2/c with a = 25.052（8）, b = 4.510（1）, c = 11.948（4） A, β = 100.992（4）°, V= 1325.2（7） A3, Mr = 314.37, Dc = 1.576 Mg.m-3, p = 0.25 mm-1, F（000） = 648, Z = 4, R = 0.034 and wR = 0.087. The preliminary biological test indicated that the compounds （2b, 2c） showed growth inhibitory activity against the gram-positive and gram-negative bacteria.

Synthesis and Crystal Structure of Trans-4-[(5-(2,4-Dichlorophenoxy)-3-methyl-1-phenyl-1H-pyrazol-4-yl)methyleneamino]-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one

The title compound trans-4-[（5-（2,4-dichlorophenoxy）-3-methyl- 1-phenyl-1H-pyrazol-4-yl）methyleneamino]- 1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 3 （C28H23Cl2N5O2, Mr = 532.41） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction analysis. It crystallizes in triclinic, space group P1- with a = 8.9438（4）, b = 11.6065（5）, c = 14.2215（6）A, α = 112.566（1）, β = 92.324（2）, γ = 102.91（1）°, V= 1315.65（10） A^3, Z = 2, Dc = 1.344 g/cm^3,μ（MoKa） = 0.282 mm^-1, λ = 0.71073 A, F（000） = 552, the final R = 0.0587 and wR = 0.1578 for 5071 observed reflections （I 〉 2σ（I））. X-ray analysis reveals that the product is a thermodynamically stable trans isomer. Intra- and intermolecular C（ 12）-H（12）…O（1） and C（28）-H（28）...O（1）# 1 hydrogen bonds were observed in the title compound.

1,5-Dimethy-4-[(3-nitro-benzylidene)-amino]-2-pheyl-1,2-dihydro-pyrazol-3-one

The title compound C18H16N4O3 （Mr = 336.35） has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The Schiff base compound is a derivative of 4-aminoantipyrine. As expected, the molecular structure adopts a trans configuration about the central C=N double bond. It crystallizes in orthorhombic, space group P2dc with a = 7.632（1）, b = 7.816（1）, c = 28.082（5） A,β = 96.18（1）°, V= 1665.48（51） A^3, Z= 4, Dc = 1.341 g/cm^3, F（000） = 704,μ = 0.094 mm^-1, the final R = 0.0448 and wR = 0.1058. Of the total 3748 collections, 3105 were unique. In the molecule there exist two different planes of pyrazoline and C（11）-C（16） phenyl ring, which are approximately coplanar （r.m.s. de deviation from the combined mean plane is 0.03 A） with the dihedral angle between them of 9.8%.

Design and Synthesis of Pyrido[1,2-e]purin-4(3H)-one Derivatives as Potential PDE 5 Inhibitors

A novel series of pyrido[ 1,2-e]purin-4（3H）-one derivatives containing polar substituents on 5＇-position were designed and prepared as potential PDE5 inhibitors. This paper reports the synthetic routes, 1H-NMR data, and the PDE5 inhibitory activities of the target compounds. The polar piperazinyl group contained （on 5＇-position） compound, 3B2, showed the highest activity among the tested derivatives but less potency than sildenafil 1.

4-[(Furan-2-ylmethylene)-amino]-1,5-dimethyl-1,2-dihyl-1,2-dihydo-pyrazol-3-one

The title compound （C16H15N3O2, Mr= 281.31） has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The Schiff base compound is a derivative of 4-aminoantipyrine. As expected, the molecular structure adopts a trans configuration about the C=N double bond. It crystallizes in the monoclinic system, space group P2 1/c with a = 11.150（3）, b = 9.906（3）, c = 13.624（4） A, β = 106.360（4）°, V= 1443.9（7） ,A^3, Z = 4, Dc = 1.294 g/cm^3, F（000） = 592,μ（MoKa） = 0.088 mm ^-1, R = 0.0577 and wR = 0.1214. Of the 5766 total reflections, 2540 were unique. In the molecule there exist two different planes of pyrazoline and O（2）-C（10） phenyl ring, which are approximately coplanar （r.m.s. de deviation from the combined mean plane is 0026 A） with the dihedral angle between them of 6.3°.

Functional Ionic Liquids Promoted Double Michael Reaction of Benzofuran-3-one or 1-1ndone and Symmetric Dienones： Construction of Spiro[benzofuran-2,1′-cyclohexane]-3-one or Spiro[cyclohexane-1,2′-indene]-1′,4（3′H）-dione Derivatives

The double Michael reactions between benzofuran-3-one or 1-indone and symmetric dienones in the presence of catalytic ionic liquids were successfully developed and spiro[benzofuran-2, 1′-cyclohexane]-3-one or spiro[cyclo- hexane-1,2′-indene]-1′,4（3′H）-dione derivatives containing a spiro quaternary stereogenic center, which widely exist in biologically active products and building blocks in organic synthesis, were obtained in excellent yields （up to 99%）. This catalytic system was also extended to the double Michael reaction of less reactive 1-indone and the desired products were also obtained in 31%-62% yields. The catalytic system was highly active and efficient for a broad of substrates under mild conditions.

Synthesis of 1,2-phenylenedimethanols by base-promoted reduction of isobenzofuran-1(3H)-ones with silane

An efficient method for preparation of substituted 1,2-phenylenedimethanols and aliphatic 1,4-diols that are valuable intermediates in organic synthesis, has been developed by the base-promoted reduction of isobenzofuran-1(3H)-ones and y-lactones with silane under mild conditions. Compared with traditional procedures using stoichiometric amounts of metal hydrides and alkyl reductants, the present method avoids the use of sensitive reagents and is operationally simple and a broad variety of functional groups are tolerated.

One-pot Combinatorial Synthesis of Benzo[4,5]imidazo- [1,2-a]thiopyrano[3,4-dJpyrimidin-4（3H）-one Derivatives

A series of novel fused tetracyclic benzo[4,5]imidazo[1,2-a]thiopyrano[3,4-d]pyrimidin-4（3H）-one derivatives were synthesized via the reaction of aryl aldehyde, 2H-thiopyran-3,5（4H,6H）-dione, and 1H-benzo[d]imidazol-2- amine in glacial acetic acid. This protocol features mild reaction conditions, high yields and short reaction time.

Three pairs of alkaloid enantiomers from the root of Isatis indigotica

Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(—)-1 and(+)-1], phaitanthrin A and epiphaitanthrin A [(—)-2 and(+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(—)-3and(+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column.Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism(ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A[(—)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products.