Pyridazine derivatives. Part 39: Reactivity of 5-iodopyridazin-3(2H)-ones in palladium-catalysed reactions

In the search for novel antiplatelet agents, convenient and efficient methods for the preparation of 2,5-disubstituted pyridazin-3(2H)-ones are reported that utilise palladium-catalysed cross-coupling reactions. A post-coupling base-promoted isomerisation has been observed during Sonogashira alkynylation of 5-iodopyridazin-3(2H)-ones (3) with 1-phenyl-2-propyn-1-ol. Variable amounts of phthalazinones were isolated as by-products during the Heck alkenylation of 3. The usefulness of the hydroxymethyl fragment as a protecting group during the synthesis of 5-substituted pyridazin-3(2H)-ones has been validated.     

Oxidative rearrangement of 2-furylcarbamates with dimethyldioxirane: a high-yielding preparation of 5-hydroxypyrrol-2(5H)-ones

A mild, general and efficient method for the oxidative rearrangement of 2-furylcarbamates to N-Boc-5-hydroxypyrrol-2(5H)-ones is reported. The feasibility of removing the Boc group from the products was demonstrated by the synthesis of two hitherto unknown 5-aryl-5-hydroxypyrrol-2(5H)-ones.     

Synthesis and biological evaluation of novel 2,4,5-triaryl-1 H-pyrazol-3（2H）-ones as inhibitors of ALK5

A series of 2,4,5-triaryl substituted 1H-pyrazol-3（2H）-ones,as ALK5 inhibitors,were desigened,synthesized and evaluated in vitro.Most compounds exhibited noticeable ALK5 inhibition activities at 1μmol/L and displayed no significant cytotoxicities at 30μmol/L.     

Unexpected facile sequential halolactamization-hydroxylation of 2, 3-allenamides with CuX(2) for the efficient synthesis of 4-halo-5-hydroxypyrrol-2(5H)-ones

[reaction: see text] 4-Halo-5-hydroxypyrrol-2(5H)-ones were synthesized from the efficient sequential halolactamization-hydroxylation reaction of 4-monosubstituted 2,3-allenamides with CuX(2) (X = Br, Cl) in high yields. Halolactamization of fully substituted 2,3-dienamide (1f) afforded 4-halo-pyrrol-2(5H)-ones.     

Visible-light-induced three-component reaction of quinoxalin-2(1H)-ones,alkenes and CF3SO2Na leading to 3-trifluoroalkylated quinoxalin-2(1H)-ones

A facile and metal-free visible-light-enabled three-component reaction of quinoxalin-2(1 H)-ones,alkenes and CF₃SO₂Na has been developed under air at room temperature.This photocatalytic tandem reaction using 4 CzIPN as the photocatalyst and air as the green oxidant,provides a mild and environmentally friendly approach to access a series of 3-trifluoroalkylated quinoxalin-2(1 H)-ones.     

有机催化靛红衍生酮亚胺与噁唑酮的不对称Mannich型加成反应

研究了手性磷酸催化的靛红衍生酮亚胺与噁唑酮的不对称Mannich型加成反应, 以良好至优秀的收率(高达97%)、 对映选择性(高达99% e.e.)以及非对映选择性(均>20∶1 d.r.)得到一系列含噁唑酮骨架的手性3,3′-二取代氧化吲哚化合物. 该反应可以进行扩大化和衍生反应.     

Assembly of 3-sulfonated 2H-pyrrol-2-ones through the insertion of sulfur dioxide with allenoic amides

Generation of 3-sulfonated 2H-pyrrol-2-ones through a three-component reaction of allenoic amides, sulfur dioxide, and aryldiazonium tetrafluoroborates under metal-free conditions is achieved. This transformation proceeds under mild conditions without the addition of catalysts or additives, giving rise to 3-sulfonated 2H-pyrrol-2-ones in moderate to good yields. Good functional group compatibility is observed. A plausible mechanism is proposed, which is initiated by aryl radicals formed in situ from aryldiazonium tetrafluoroborates and DABCO·(SO₂)₂. Additionally, excellent chemoselectivity and regioselectivity are presented in this transformation.     

Diastereoselective synthesis of 3,4-disubstituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones: chirality transfer in the enantioselective synthesis of ethyl (+)-(3S,4aS,7aS)-1-oxo-octahydro-1H-cyclopenta[c]pyridine-3-carboxylate

The base-mediated reaction of enantiomerically pure -sulfinylketimine (+)-1 with (E)-,β-disubstituted propenoate esters afforded 3,4-disubstituted-5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones 9-13 and 14 with high or complete diastereoselectivity. A sole diastereomer of the four possible ones, with regard to the nature of ester, was isolated, which revealed the stereocontrol of the chiral sulfinyl group in the Michael reaction and transenolization steps. In addition, the enantioselective synthesis of ethyl (+)-(3S,4aS,7aS)-1-oxo-octahydro-1H-cyclopenta[c]pyridine-3-carboxylates (+)-17 is described (five steps; 47% yield; ee 97%). The absolute configuration of stereocentres introduced in (+)-17 was assigned on the basis of ¹H NMR data.     

Study of the alkylation of chlorosilanes. Part I. Synthesis of tetra(1H, 1H, 2H, 2H-polyfluoroalkyl)silanes

The synthesis and structural characterization of tetra(1H, 1H, 2H, 2H-polyfluoroalkyl)silaneswith the same or different chain lengths C_nF_2n+1 linked to Si (1n6) is reported.

When the synthesis was effected from chlorosilanes and fluorinated organomagnesiumor organolithium reagents, the trialkylsilanes were obtained. The last fluorinated chainwas introduced either via a fluoroalkyllithium reagent or by hydrosilylation of thetrialkylsilanes.

Some properties and characterization by ¹H, ¹⁹F and ²⁹Si NMR spectroscopy of the1H, 1H, 2H, 2H-polyfluoroalkylsilanes are described.     

Stereoselective |2+2| photocycloaddition of chiral 2(5H)-furanones to alkenes

The steric and stereoelectronic dependence of the diastereoselectivity in the photochemical |2+2| cycloaddition of chiral 2(5H)-furanones to alkenes is investigated to prepare eventually cyclobutanic natural products. It is shown that the alkenes approach to different chiral 5-substituted 2(5H)-furanones mainly by the less hindered side.     

Alignment behaviour of symmetrical and asymmetrical triphenylenes possessing fluoroalkylated side chains on modified substrates

The alignment behaviour of triphenylene-based compounds possessing fluoroalkylated and alkyl side chains was investigated for the hexagonal columnar (Col_h) mesophase on polyimide-, cetyltrimethylammonium bromide (CTAB)-, and indium tin oxide-coated glass substrates by polarizing optical microscopy. It was found that 2,6,10-trinonyloxy-3,7,11-tris(1H,1H,2H,2H,3H,3H-perfluorononyloxy)triphenylene and 2,6,11-trinonyloxy-3,7,10-tris(1H,1H,2H,2H,3H,3H-perfluorononyloxy)triphenylene exhibit spontaneous homeotropic alignment on these substrates. On the other hand, it was found that 2,6,10-triheptyloxy-3,7,11-tris(1H,1H,2H,2H,3H,3H-perfluoroheptyloxy)triphenylene, 2,6,11-triheptyloxy-3,7,10-tris(1H,1H,2H,2H,3H,3H-perfluoroheptyloxy)triphenylene, 2,6,10-trihexyloxy-3,7,11-tris(1H,1H,2H,2H,3H,3H-perfluorohexyloxy)triphenylene, 2,6,11-trihexyloxy-3,7,10-tris(1H,1H,2H,2H,3H,3H-perfluorohexyloxy)triphenylene, 2,6,10-tributyloxy-3,7,11-tris(1H,1H,2H,2H,3H,3H-perfluorobutyloxy)triphenylene and 2,6,11-tributyloxy-3,7,10-tris(1H,1H,2H,2H,3H,3H-perfluorobutyloxy)triphenylene do not show such spontaneous homeotropic alignment on these substrates. These results indicate that the spontaneous homeotropic alignment of the Col_h phase could be easily attained by the introduction of an appropriate length of the fluoromethylene chains in the peripheral parts of discogens. Therefore, it is suggested that the balance between the hydrocarbon part including the triphenylene core and the fluoroalkyl part determines the alignment control behaviour. Furthermore, it was found that alignment behaviour is independent of the rotation symmetry of the chemical structure but is dependent on the number of fluoromethylene chains in the chemical structure.     

Synthesis of 2,3-dihydroquinazolin-4(1H)-ones catalyzed by zirconium (IV) chloride as a mild and efficient catalyst

2, 3-Dihydroquinazolin-4 (1H)-ones have been synthesized in the high to excellent yields via condensation of 2-aminobenzamide with aldehydes and ketones in the presence of catalytic amount of ZrCl₄ in EtOH at room temperature. Mild reaction conditions, clean reaction media, simple workup and easy purification are advantages of this methodology.     

Crystallographic and ab initio theoretical studies of (2R,3R)-1-methyl-5-oxo-2-phenyltetrahydro-1H-pyrrole-3-carboxylic acid. The comparison of chiral (I) and racemic (II) structure

Crystal and molecular structures of (2R,3R)-1-methyl-5-oxo-2-phenyltetrahydro-1H-pyrrole-3-carboxylic acid (I) and (2R^*,3R^*)-1-methyl-5-oxo-2-phenyltetrahydro-1H-pyrrole-3-carboxylic acid (II) are presented. The alternative packings were studied using ab initio quantum-chemical methods. Energies of hydrogen bonds for real and model cases are discussed. Infinite chains of molecules instead of carboxylic acid dimers were observed.     

左氧氟沙星3-芳苄叉基-喹啉-4-酮衍生物的合成及抗肿瘤活性

为进一步发现提高氟喹诺酮抗肿瘤活性的有效结构修饰策略,基于片段药物设计原理,通过喹啉-4(1H)-酮与芳香醛缩合反应合成了(S)-6-氟-7-(4-甲基-哌嗪-基)-8,1-(1,3-氧丙基)-3-芳苄叉基-2,3-二氢-喹啉-4(1H)-酮(3a-3l)目标化合物。 体外抗肿瘤活性结果表明,所合成的12个新化合物的活性均强于母体左氧氟沙星,其中F、Cl、Br取代的卤苯基化合物对人肝癌细胞株(SMMC-7721)和人胰腺癌细胞株(Capan-1)的半数抑制浓度(IC₅₀)低于其它取代基化合物,尤其是氯苯基化合物(3k)与对照抗肿瘤药阿霉素活性相当。 为此,芳苄叉基替代C-3羧基构建的3-芳苄叉基-喹啉-4-酮化合物有助于提高氟喹诺酮的抗肿瘤活性,提示α,β-不饱和酮片段作为一个有发展前景的氟喹诺酮的候选修饰基团值得进一步发展。     

A new method for the preparation of 2,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones

Several 2,3-cycloalkeno-5,6-cycloalkeno-4H-pyran-4-ones, such as 2,3,5,6-bicyclopenteno-4H-pyran-4-one and 1,2-dihydronaphtho[3,4-b]cyclopenteno[1,2-e]-4H-pyran-4-one, were synthesized conveniently by the reaction of a cyclic ketone enamine and diacylchloride. This reaction allows a new method for preparation of these compounds, which may be the precursors for the synthesis of some useful heterocycles.     

Surfactants having polyfluoroalkyl chains. II. Syntheses of anionic surfactants having two polyfluoroalkyl chains including a trifluoromethyl group at each tail and their flocculation-redispersion ability for dispersed magnetite particles in water

Anionic surfactants having two polyfluoroalkyl chains per molecule, i.e. the sodium salt of bis(1H, 1H, 2H,2H-heptadeca-fluorodecyl)-2-sulfosuccinate, CF₃(CF₂)₇(CH₂)₂OCOCH₂CH(SO₃Na)COO(CH₂)₂(CF₂)₇CF₃, the sodium salt of bis(1H, 1H, 2H, 2H-tridecafluoro-octyl)-2-sulfosuccinate, CF₃(CF₂)₅(CH₂)₂OCOCH₂CH(SO₃Na)COO(CH₂)₂(CF₂)₅CF₃, and the sodium salt of bis(1H, 1H, 2H, 2H-nonafluorohexyl)-2-sulfosuccinate, CF₃(CF₂)₃(CH₂)₂OCOCH₂CH(SO₃Na)COO(CH₂)₂(CF₂)₃CF₃, have been prepared from maleic anhydride, the corresponding alcohols possessing a polyfluoroalkyl chain and sodium hydrogen sulfite. The flocculation and redispersion abilities of these surfactants for dispersed magnetic particles in water have been examined to investigate the effect of the chain length. It was found that this ability was enhanced by an increase in the chain length. The contact angles for water for pelleted surface-modified magnetite have been measured. In order to compare this ability and the contact angles, data for other fluorinated surfactant have been obtained. The Kraff point, the surface tension and the pNa of the aqueous surfactant solutions have also been measured.     

H, C, N NMR, ESI mass spectral and single crystal X-ray structural characterization of three spiro[pyrrolidine-2,3′-oxindoles]

Three spiro[pyrrolidine-2,3′-oxindoles], 1,1′,2,2′,5′,6′,7′,7′a-octahydro-2-oxo-1′-phenyl-spiro[3H-indole-3,3′-[3H]-pyrrolizine]-2′-carboxylic acid methyl ester (1), 1,1′,2,2′,5′,6′,7′,7′a-octahydro-2-oxo-1′-nitro-2′-phenyl-spiro[3H-indole-3, 3′-[3H]-pyrrolizine] (2) and 1,1′,2,2′,5′,6′,7′,7′a-octahydro-2-oxo-1′-nitro-2′-(4″-chlorophenyl)-spiro[3H-indole-3,3′-[3H]-pyrrolizine] (3) have been synthesized and their ¹H, ¹³C and ¹⁵N spectra assigned. The chemical shift assignments are based on Pulsed Field Gradient (PFG) Double Quantum Filter (DQF) ¹H, ¹H correlation spectroscopy (COSY), PFG ¹H, ¹³C Heteronuclear Multiple Quantum Coherence (HMQC) and PFG ¹H,X (X = ¹³C and ¹⁵N) Heteronuclear Multiple Bond Correlation (HMBC) experiments. The single crystal X-ray structures of 1–3 have been determined. Compounds 1 and 2 crystallized in monoclinic space group C2/c and compound 3 in monoclinic space group P2₁/c, respectively. Also the ESI-TOF MS data of 1–3 are given.     

Design,Synthesis and Insecticidal Activities of Novel 5-Alkoxyfuran-2(5H)-one Derivatives

A series of novel 5?alkoxyfuran-2(5H)-one derivatives was synthesized, and characterized by 1H NMR, 13C NMR and HRMS. Biological activities of all the title compounds were evaluated systematically. Preliminary bioassays indicated that most of the compounds exhibited moderate insecticidal activities against Aphis craccivora and Nilaparvata lugens at 100 mg/L. Compounds 4h and 4w exhibited 100% mortality rate against Aphis craccivora at 100 mg/L, and compound 4h exhibited good mortality rate against Aphis craccivora and Nilaparvata lugens (60% and 75%, respectively) even at 4 mg/L. The results demonstrated the impact of various chemical groups on insecticidal activities and provided a potential clue for further exploring novel high-effective broad-spectrum insecticides.     

Crystal structures of an isomeric pair of 3-methylthio-5-amino-1,2,4-triazoles

The structures of an isomeric pair: 1-[2-(2,6-dichlorophenoxy)-ethyl]-3-methylthio-5-amino-1H-1,2,4-triazole (IV) and 2-[2-(2,6-dichlorophenoxy)-ethyl]-3-methylthio-5-amino-2H-1,2,4-triazole (V) have been established by X-ray crystallography from diffractometer data. Crystals of IV are monoclinic, space group P2₁/c with a = 11.220(1), b = 10.005(3), c = 12.784(3) Å, β = 91.99(1)°, Z = 4, D_c = 1.478 g cm⁻³. Crystals of V are orthorhombic, space group Pbca with a = 7.618(2), b = 14.289(4), c = 26.494(7) Å, Z = 8, D_c = 1.470 g cm⁻³. The structures determined by direct methods were refined to R = 0.060 for 1931 reflections of IV and R = 0.061 for 1315 reflections of V. The X-ray analysis corroborated the structures assigned to the isomeric pair on the basis of proton coupled ¹³C-NMR spectra. The features (i.e. the sequence of the endocyclic bond angle magnitudes) of the planar s-triazole rings are governed by the same rules reported recently by Kálmán and Argay [J. Mol. Struct., 102 (1983) 391] discussing the structures of the related I, II and III compounds. In contrast to I, II, III and IV the S(6)---C(7) bond of V is almost perpendicular to the best plane of the s-triazole ring C(7)---S(6)---C(3)---N(4) = −79.0(7)°. This unusual orientation of the S-methyl bond is created by the steric hindrance of the very same vicinal 2-ethyl (C(9)H₂---C(10)H₂) moiety once within the molecule V and the second time as the part of a symmetry equivalent molecule at a distance of −a (7.618 Å). These molecules are fixed together by two infinite helices of hydrogen bonds formed around the screw axis 2, (X, 1/4, 1/2) via an intermediate V molecule at (x − 1/2, 1/2 − y, 1 − z).     

Asymmetric alcoholysis of 2-phenyl-5(4H)-oxazolones by the catalytic mixture of cyclo[(S)-His-(S)-Phe] with chiral auxiliaries

Some derivatives of dipeptides containing a His residue catalyzed the ring opening of 2-phenyl-4-benzyl-5(4H)-oxazolone by methanol. The mixture of cyclo[(S)-His-(S)-Phe] (CHP) with chiral auxiliaries which possess both a hydrogen-bond donor and a hydrogen-bond acceptor was a more effective and enantioselective catalyst than the CHP alone. The influence of racemic and the two enantiomerically pure auxiliaries on the cyclo[(S)-His-(S)-Phe]-catalyzed alcoholysis of the 5(4H)-oxazolone was different. A mixture of CHP with -diisopropyl tartrate catalyzed the enantioselective ring opening of 2-phenyl-4-benzyl-5(4H)-oxazolone by methanol, ethanol and n-butanol, preferentially affording the N-benzoyl- -phenylalaninates (20–39% e.e.).