Novel synthesis of 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde:A key intermediate of Losartan

A novel method for synthesis of 2-butyl-5 -chloro-3H-imidazole-4-carbaldehyde 2, a key intermediate of Losartan was reported. The compound 2 was synthesized from starting material dimethyl malonate 6 and n-valeronitrile 8 by six steps with an overall yield of 40%. The key step including the reaction of compound 5 with POCl3/DMF followed by hydrolysis to give compound 2 with the yield of 68%.

Oxidation of 4-chloro-3-methylphenol using zeolite Y-encapsulated iron(Ⅲ)-,nickel(Ⅱ)-,and copper(Ⅱ)-N,N'-disalicylidene-1,2-phenylenediamine complexes

The degradation of 4-chloro-3-methylphenol（PCMC）using zeolite-encapsulated iron（III）,nickel（II）,and copper（II）complexes of N,N’-disalicylidene-1,2-phenylenediamine as catalysts,in a heterogeneous Fenton-like advanced oxidation process,was studied.The physicochemical properties of the catalysts were determined using powder X-ray diffraction,thermogravimetric analysis,Brunauer–Emmett–Teller surface area analysis,Fourier-transform infrared spectroscopy,elemental analysis,and scanning electron microscopy.The effects of four factors,namely initial H2O2 concentration,catalyst dosage,temperature,and pH,on the degradation of a model organic pollutant were determined.The results show that at low acidic pH,almost complete removal of PCMC was achieved with the iron（III）,nickel（II）,and copper（II）catalysts after 120 min under the optimum reaction conditions：catalyst dosage 0.1 g,H2O2 concentration 75 mmol/L,initial PCMC concentration 0.35mmol/L,and 50 °C.The reusability of the prepared catalysts in PCMC degradation was also studied and a possible catalyst deactivation mechanism is proposed.The possible intermediate products,degradation pathway,and kinetics of PCMC oxidation were also studied.

Two New Schiff Bases Based on 5-Chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde: Syntheses, Crystal Structures and Properties

Two new Schiff bases based on 5-chloro-3-methyl-1-phenyl-1 H-pyrazole-4-carbaldehyde, namely, N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-4-morpholinoaniline(Ⅲa) and N-((5-chloro-3-methyl-1-phenyl-1 H-pyrazol-4-yl)methylene)-3-fluoro-4-morpholinoaniline(Ⅲb), were synthesized and characterized by IR, LC-MS, 1 H NMR and 13 C NMR spectroscopy. Meanwhile, the three-dimensional configurations of the two title compounds were further characterized by single-crystal X-ray diffraction analyses. Both the compounds are thermodynamically stable trans-isomers. Moreover, the fluorescence properties and antioxidant activities against DPPH of the two target compounds have been investigated, and the results showed that the title compounds both have fluorescence performance and certain antioxidant activities against DPPH radical.

Synthesis,Crystal Structure and Anti-tumor Activity of 2-(2-Chloro-4-nitrophenyl)-4-(4-chlorophenyl)-3a,4-diethoxy-2,3,3a,4-tetrahydrochromeno[3,4-d][1,2,3]diazaphosphole

The title compound 2-（2-chloro-4-nitrophenyl）-4-（4-chlorophenyl）-3a,4- diethoxy- 2,3,3a, 4-tetrahydrochromeno[3,4-d][1,2,3]diazaphosphole 2 （C29H30Cl2N3O7P, Mr = 633.44） was synthesized and its structure was characterized by IR, MS, ^1H NMR, ^13C NMR, ^31p NMR, elemental analysis and single-crystal X-ray diffraction. It crystallizes in triclinic, space group P1^-, a = 9.1549（3）, b = 10.7168（4）, c = 17.6272（6）A, α = 102.9363（12）, β = 90.2713（9）, γ = 117.4265（10）°, V= 1484.41（9）A^3, Z= 2,μ（MoKa） = 0.323, F（000） = 658, Z= 2, De= 1.417 g/cm^3, the final R = 0.0687 and wR = 0.2066 for 4943 observed reflections （I 〉 2σ（I））. X-ray analysis reveals that the diazaphospholine ring is almost planar and the two ethoxy groups bonded on the 3a- and 4-positions are in trans configurations. Its antiproliferative activity was also tested in vitro against four human tumor cell lines.

(Z)-N-(3-(2-Chloro-4-nitrophenyl)-4-methylthiazol-2(3H)-ylidene) Pivalamide: Synthesis and Crystal Structure

Synthesis of the title compound was carried out by base-catalyzed cyclization of 1-pivaloyl-3-(2-chloro-4-nitrophenyl) thiourea with α-bromoacetone produced in situ. The structure was confirmed by the spectroscopic and elemental analysis and single crystal X-ray diffraction data. It crystallizes in the triclinic space group P-1 with unit cell dime sions a = 8.7137(10), b = 10.2010(14), c = 10.6593(13), α = 62.671(9), β = 82.701(10), γ = 79.762(10), V = 827.21(8) ?3, Z = 2.

活性氯酚3-氯-3’,4’-二羟基二苯甲酮固体分散体的制备及体外溶出研究

目的制备活性氯酚3-氯-3’,4’-二羟基二苯甲酮(HP46)的固体分散体(solid dispersion,SD),以提高HP46的体外溶解度和溶出度。方法以聚乙烯吡咯烷酮(PVPK30)为载体,吐温(Tween80)为表面活性剂,采用溶剂法制备HP46的固体分散体,优化固体分散体组成,并进行体外溶出研究。运用粉末X-射线衍射(XRD)和差示热量扫描(DSC)分析固体分散体中药物的分散状态。结果 HP46固体分散体组成的最优质量比为HP46-PVPK30-Tween80 1∶3∶1,XRD和DSC结果表明HP46以无定型或分子状态存在于载体中,体外溶解度和溶出速率显著提高,溶解度为1 319.4μg/ml,在20 min内累积溶出率为77.23%,溶解度和溶出度较原料药分别提高约30倍和8倍。结论以PVPK30为载体,加入表面活性剂Tween80,可有效提高HP46的溶解度和溶出度,固体分散体最优质量比为HP46-PVPK30-Tween80 1∶3∶1。

Crystal Structure and Biological Activities of (R)-N′-[2-(4-Methoxy-6-chloro)-pyrimidinyl]-N-[3-methyl-2-(4-chlorophenyl)butyryl]-urea

The title compound （R）-N′-[2-（4-methoxy-6-chloro）-pyrimidyl]-N-[3-methyl-2-（4- chlorophenyl）butyryl]-urea has been synthesized, and its crystal structure and biological behaviors were studied. Crystallographic data： C17H18C12N4O3, Mr = 397.25, monoclinic, space group P21/c, a = 12.331（2）, b = 14.025（3）, c = 23.085（5） A, β = 99.607（4）°, Z = 8, V = 3936.2（13） A3, Dc = 1.341 g/cm^3, F（000） = 1648, R = 0.0718, wR = 0.1585 and/t（MoKα） = 0.353 mm^-1. The preliminary biological tests showed that the title compound has definite insecticidal and fungicidal activities.

A highly enantioselective synthesis of 5- (ι-menthyloxy) -4-substituted-3-chloro-2(5H) -furanones

In this paper, stereocontrolled tandem Michael addition-elimination reaction of the novel chiral source, S-(ι-menthyloxy)-3,4-dichloro-2(5H)-furanone, with various thiols and amines has been investigated. A series of new enantiomerically pure compounds, 5-(ι-menthyloxy)-4-substituted-3-cnloro-2(5H)-furanones, were obtained in good yields with d. e.(?)98% under mild conditions.

反相高效液相色谱法测定原料药3-氯-3’，4’-二羟基二苯甲酮的含量及有关物质

目的：建立反相高效液相色谱（RpHPLC）法测定原料药3-氯3’，4’-二羟基二苯甲酮（HP46）的含量及有关物质。方法：采用Diamonsil C1-（250mm×4．6mm，5μm）色谱柱，以甲醇-乙腈-水（用磷酸调节pH至3．0）（65：5：30）为流动相，流速0．8mL·min，检测波长243nm，柱温25℃，外标法测定HP46含量，自身对照法测定有关物质。结果：有关物质与主药分离良好，主药含量高于99％，HP46在3．0-180mg·L-1范围内线性关系良好（r=0．9999），最低检测限1mg·L-1。结论：建立的高效液相色谱方法灵敏性和专属性好，适用于原料药HP46的质量控制、有关物质检测和稳定性检查。

Simultaneous Determination of Ultraviolet Absorbers and Antibacterial Agents in Textiles by Ultra-High Performance Liquid Chromatography/Orbitrap High Resolution Mass Spectrometry

This paper reported a new analytical method for the simultaneous determination of seven benzotriazole ultraviolet absorbers and seven antibacterial agents in textiles. After ultrasonic extraction for the textile samples in methanol, the solutions were analyzed by ultra-high performance liquid chromotagraphy/orbitrap high resolution mass spectrometry (UPLC/Orbitrap HRMS). It showed that a good chromatographic separation for these target compounds was achieved by a Hypersil GOLD column (100 mm × 2.1 mm × 1.9 μm) with a gradient elution of methanol and 0.1% aqueous formic acid solution (containing 0.5 mmol/L ammonium acetate). Triclosan and 4-chloro-3,5-dimethyl phenol (PCMX) were detected by the orbitrap HRMS in an electrospray ionization (ESI) negative mode while the other twelve target compounds were detected by orbitrap HRMS in ESI positive mode. Full scan experiment was performed over the range from m/z 100 to m/z 500. These target compounds were routinely detected with mass accuracy below 2 × 10-6 (2 ppm) at the optimized conditions. The results showed that the limits of detection (LODs) were in the range from 0.1 to 0.3 μg/kg. The blank samples were spiked at three levels and their average recoveries varied from 80.5% to 96.3% while the relative standard deviation (RSD) changed from 3.2% to 9.9%. The present method was also applied for the determination of those ultraviolet absorbers and antibacterial agents in the commercial textiles.

马来酸氟吡汀的合成

通过对马来酸氟吡汀的合成研究,确定并打通了马来酸氟吡汀的合成路线,该工艺条件与其他路线比较,具有起始原料易得、产品收率高、操作简便等优点。即以2-氨基-3-硝基-6-氯吡啶为原料与对氟苄胺反应,然后氢化还原后,滤液进行酰化反应得到氟吡汀碱,经五步反应得到马来酸氟吡汀,结构经1H-NMR确认,总收率77%,含量大于99.9%,产品质量符合2010版药典要求。

Synthesis of Bridged Dianiline Containing Fluorine

Four novel bridged dianilines containing fluorine were synthesized using 4-chloro-3, 5-dinitrobenzotrifluoride and diamine by two step condensation and reduction. The structures of corresponding compounds were determined by means of IR, NMR and elemental analysis.

A Novel One-Pot and Efficient Procedure for Synthesis of New Fused Uracil Derivatives for DNA Binding

Hydrazinolysis of 6-chloro-1-methyluracil followed by condensation of the product with different aromatic aldehyde gives the respective hydrazones which undergoes oxidative cyclization using thionyl chloride to obtain pyrazolo[3,4-d]pyrimidines in good yields. On the other hand, nitrosation of 6-aminouracils followed by the reaction with different arylidineanilines gives new xanthine derivatives. Finally, indenopyrrolopyrimidine and indenopteridine are obtained in good yields via the reaction of 6-aminouracils and 5,6-diaminouracil with ninhydrin respectively. The newly synthesized compounds show binding, chelation and fragmentation of the nucleic acid DNA.

Purification and characterization of a novel carbonyl reductase with high stereo-selectivity

A novel NADPH-dependent carbonyl reductase was separated from Candida parapsilosis CCTCC 203011.The enzyme gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE),which was purified through ammonium sulfate,Diethylamino Ethanol(DEAE)sepharose Fast flow(FF),phenyl-sepharose FF and blue sepharose FF chromato graphy from cell-free extract.The molecular mass of the enzyme was about 30 kDa.The optimum pH and temperature for reduction were 4.5℃ and 35℃,respectively.The Cu2+had strong restrictive effect on enzyme activity.In addition,the carbonyl reductase was an enzyme with high substrate specificity and stereo-selectivity,and showed high asymmetric reduction activity towards a-hydroxyacetophenone and ethyl 4-chloro acetoacetate.For the asymmetric reduction of a-hydroxyacetophenone and ethyl 4-chloro acetoacetate,(S)-1-phenyl-1,2-ethanediol and(R)-ethyl 4-chloro-3-hydroxybutanoate were produced by the purified enzyme,with the 100% and 94.3%e.e.value,respec-tively.Therefore,the enzyme could be one of the effective biocatalysts for asymmetric synthesis of chiral alcohols.The amino acid sequences of one peptide from the purified enzyme were analyzed by LC-MASS-MASS,and the car-bonyl reductase showed some identity to the hypothetical protein CaO19.10414 reported.