联苯吡菌胺关键中间体3′,4′-二氯-5-氟-1,1′-联苯-2-胺的合成

为获得联苯吡菌胺关键中间体3′,4′-二氯-5-氟-1,1′-联苯-2-胺的适合工业化生产工艺路线,对其合成工艺进行了优化。以3,4-二氯溴苯和2-溴-4-氟苯胺为原料,经格氏和Suzuki偶联2步反应合成了3′,4′-二氯-5-氟-1,1′-联苯-2-胺,其结构经1H NMR、MS表征确证,并对合成条件进行了优化。优化条件下,3′,4′-二氯-5-氟-1,1′-联苯2-胺合成总收率61.9%,纯度98%。该工艺成本低,收率高,具有工业化生产前景。

2-乙酰吡啶缩(2'-吡啶亚胺基)肼与钴显色反应的研究

研究了钴与新试剂2-乙酰吡啶缩（2＇-吡啶亚胺基）肼（LB2-205）的显色反应条件,建立了光度法测定药物中微量钴的新方法.在pH=7.5左右的弱碱性介质中,Co（Ⅱ）与LB2-205反应生成摩尔比为1∶2的橙黄色的络合物,在360-500 nm范围内都有较大吸收,其表观摩尔吸光系数4ε40=1.02×10^4L.mol^-1·cm^-1,钴（Ⅱ）含量在0.300-6.00 mg·L^-1范围内符合比尔定律,该方法可用于维生素B12和水样中微量钴的测定,加标回收率在96.4%-99.5%之间.

新显色剂2-乙酰吡啶缩(-2’-吡啶亚胺基)肼与镍的显色反应研究

基于新试剂2-乙酰吡啶缩（-2’-吡啶亚胺基）肼与镍（Ⅱ）的显色反应,建立了用2-乙酰吡啶缩（-2’-吡啶亚胺基）肼光度法测定微量镍的新方法.在pH 7.5左右的介质中,N i2＋与2-乙酰吡啶缩（-2’-吡啶亚胺基）肼反应生成摩尔比为1∶1的黄色络合物,最大吸收波长为420 nm,其表观摩尔吸光系数ε420=1.45×104L.mol-1.cm-1,镍含量在0.10~4.00mg.L-1范围内符合比尔定律.所拟方法成功用于茶叶及环境水样中微量镍的测定,加标回收率在97.0%~103.2%之间.

Mn（I）与1，1，4，7，10，10－六（2－甲基苯并咪唑基）三乙四胺的多核配合物的合成和表征

合成了３种新的锰（Ⅱ）的多核配合物，分别为Ｍｎ３（Ｌ）Ｃｌ６·１２Ｈ２Ｏ（Ⅰ），Ｍｎ２（Ｌ）Ｃｌ４·８Ｈ２Ｏ（Ⅱ）和Ｍｎ２（Ｌ）（ＮＯ３）４·９Ｈ２Ｏ（Ⅲ）．其中Ｌ为１，１，４，７，１０，１０－六（２－甲基苯并咪唑基）三乙四胺（ＴＴＨＢ），由三乙四胺六乙酸与邻苯二胺共热缩合而得．根据配合物的摩尔电导、红外光谱、电子光谱和顺磁共振及元素分析。

Synthesis of 3-Chloro-2-Nitrotoluene

The synthesis of 3 chloro 2 nitrotoluene using 2,6 dichloroaniline as starting material by diazotization, substitution, condensation, decarboxylic reaction was studied and the best conditions of the synthetic procedures were confirmed. Dichloronitrobenzene was obtained in 78.9% yield based on 2,6 dichloroaniline. The reaction of 2,6 dichloronitrobenzene and methyl cyanoacetate with potassium carbonate catalyst in N,N dimethyl formamide gave methyl 2 cyano 2 (3′ chloro 2′ nitrophenyl) acetate in 80.2% yield. The third procedure product 3 chloro 2 nitrophenylacetic acid was obtained by hydrolysis in 82.6% yield. Decarboxylation reaction of 3 chloro 2 nitrophenylacetic acid produced 3 chloro 2 nitrotoluene in 72.9% yield.The structure of products was identified by IR and NMR.

Experimental and Density Functional Theory Calculation Studies on Raman and Infrared Spectra of 1,1＇-Binaphthyl-2,2＇-diamine

The IR absorption, visible excited normal Raman, and UV-excited near-resonant Raman （UVRR） spectra of 1,1＇-binaphthyl-2,2＇-diamine （BINAM） were measured and analyzed. Density functional theory calculations were carried out to investigate its vibrational frequencies, infrared absorption, normal Raman, and near-resonance Raman intensities. The observed Raman and IR bands of BINAM were assigned with respect to the local vibrations of substituted 2-naphthylamine. Several Raman bands of BINAM were found selectively enhanced in the UVRR in comparison with the normal Raman spectrum. Possible excited state geometry distortion was discussed based on the resonance Raman intensity analysis.

Selective arylation/annulation cascade reactions of 2-alkynylanilines with diaryliodonium salts

An efficient Cu catalyzed selective arylation/annulation cascade reaction of 2-alkynylanilines with diaryliodonium salts was developed.This reaction was selective to N-arylation instead of C-arylation,which provides a simple synthetic method for N-aryl indoles.

Synthesis and Crystal Structure of 4-Salicylimine-3, 5-bis(2-hydroxyphenyl)-1, 2, 4-triazole JI Bao-Minga

The title compound, 4-salicylimine-3, 5-bis(2-hydroxyphenyl)-1, 2, 4-triazole, was obtained by the condensation reaction of 4-amino-3, 5-bis(2-hydroxyphenyl)-1, 2, 4-triazole with salicylaldehyde in methanol. The crystal structure (C21H16N4O3, Mr = 372.38) belongs to monoclinic system, space group P21/n with a = 10.507(2), b = 16.878(3), c = 11.199(2) ? = 110.86(3), V = 1855.9(6) ?, Z = 4, Dc = 1.333 g/cm3, F(000) = 776, (MoK? = 0.092 mm-1, R = 0.0552 and wR = 0.1095 for 1920 reflections ( I > 2.0(I) ). The analytical results of crystal structure show that there are two different non-covalent interactions in the compound. One is hydrogen bond, and the other p-p stacking interaction. These two types of non-covalent interactions play an important role in the packing of crystal.

C-H…O Hydrogen Bonds and π…π Interaction and the Crystal and Molecular Structures of 3-Nitro-benzylideneaniline-methyl-2’

The title compound (C14H12N2O2, Mr = 240.26) crystallizes in the monoclinic system, space group P21/a with a = 7.394(1), b = 21.334(3), c = 7.423(1) ? b = 89.82(1)? V = 1170.8(3) ?, Z = 4, Dc = 1.363 g/cm3, m(MoKa) = 0.93 cm-1 and F(000) = 504.00. The final R and wR are 0.0440 and 0.1370 for 2153 observed reflections (I > 2s(I)), respectively. The dihedral angle between the two phenyl rings is 52.9 and that between the NO2 group and its attached ring is 3.0. In the crystal, molecules are stacked along [100] through p…p interactions. The CH…O hydrogen bond (3.403 ? 120.4? laterally connects the stacks along [010] to form networks (001) which are further anti- parallelly connected by CH…O (3.382 ? 142.9) and p…p interactions extending along [001]. Also presented here is a brief study on the CH…O hydrogen bonds in nitro-substituted benzyl-ideneanilines which can be classified into five types, namely, )5(12R, )4(21R, )8(22R, )6(12R and )7(22R, with the first three occurring more often.

Catalytic role of Cu(I) species in Cu_2O/CuI supported on MWCNTs in the oxidative amidation of aryl aldehydes with 2-aminopyridines

Cu2O and Cul were supported on multiwalled carbon nanotubes （MWCNTs） using a wet impregna- tion method, and the resulting materials were fully characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy with energy dispersive X-ray spectroscopy, transmission electron microscopy, and temperature-programmed desorption with ammonia analysis. The results of these experiments revealed that Cu2O and CuI were deposited on the MWCNTs in the cubic and γ phases, respectively. These results also showed that the Cu-containing MWCNTs exhibited weak to strong electron-accepting （Lewis acidic） properties. The catalytic activities of these materials were studied for the synthesis of biologically significant N-（pyridin-2-yl）benzamides via the oxidative amidation of aryl aldehydes with 2-aminopyridines. The yields of the products were in the range 50%-95% with 100% selectivity. Notably, the CuI/MWCNT catalyst was much more effective than the Cu2O/MWCNT catalyst with respect to the isolated yield of the product, although the latter of these two catalysts exhibited much better recyclability. A preferential interaction was observed between the polar nature of the acid-activated MWCNTs and the ionic Cu2O compared with covalent CuL The differences in these interactions had a significant impact on the rate of the nucleophilic attack of the amino group of 2-aminopyridine substrate on the carbonyl group of the aryl aldehyde.

Determination of 2-Amino-6-Cyclopropylamino-9-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl)purine in Rat Plasma,Urine and Liver Homogenates by High Performance Liquid Chromatography

Aim To develop a simple and specific high-performance liquid chromatographic(HPLC) method, suitable for the pharmacokinetic studies in vivo, to determine the concentrations of2-amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)purine (Cyclo-D4G, IMGprodrug) in rat plasma, urine and liver homogenates. Methods Chromatography was performed with C-18Hypersil ODS column and a mobile phase of 7% (v/v) acetonitrile in phosphate buffer, pH 7.40, withUV detection at 283 nm. Results The average extraction recovery of Cyclo-D4G in rat plasma and urinewas 100.1% over its linear range of 0.5 - 80 μg·mL^(-1). The accuracy of the assay was 99.4% .The intra-and inter-day RSDs were less than 9.0% . Conclusion The analytical method was found to beapplicable, reliable and suitable for pharmacokinetic studies.

Crystal Structure and Electrochemical Behavior of Copper Complex with 6-Hydroxymethyl-substituted Tris(2-pyridylmethyl) Amine, [CuCl(C_(19)H_(20)N_4O)]ClO_4

A Cu(II) complex [CuCl(C19H20N4O)]ClO4 1 containing hydroxymethyl substituted TPA (TPA = tris(2-pyridylmethyl)amine) was prepared. It crystallizes in monoclinic, space group P21/c with a = 11.7628(2), b = 13.0083(3), c = 15.11280(10) ?, β = 108.724(2)°, V = 2190.09(7) ?3, Mr = 518.83, Z = 4, T = 293(2) K, Dc = 1.574 g/cm3, μ = 1.280 mm-1, F(000) = 1060 and S = 1.085. The final R = 0.0543 and wR = 0.1433 for 2693 observed reflections with I >2σ(I). The penta- coordinated copper (II) complex assumes an approximate square pyramidal geometry. Cyclic volta- mmetry measurement of the complex showed a quasi-reversible CuII/CuI redox couple with E1/2 = –0.467 v and ?E = 68 mv.

Synthesis and Crystal Structure of a New Hexadentate Ligand N,N'-Bis(di(2-pyridyl)methyl)ethylenediamine

The reaction of di(2-pyridyl)ketone with ethylenediamine produced hexadentate Schiff base 1 which can be reduced to form a new ligand N,N-bis(di(2-pyridyl)-methyl)ethylene- diamine (BDPM) in ethanol solution. The two compounds were characterized by elemental analyses and spectroscopic methods. Their structures were determined by X-ray diffraction study. Crystal data for 1: C24H20N6, Mr = 392.5, monoclinic, P21/c, a = 13.871(3), b = 13.510(2), c = 12.153(2) ? b = 112.97(2)? Z = 4, V = 2094.1(6) ?, Dc = 1.245 g/cm3, m(MoKa) = 0.078 mm-1, F(000) = 824, the final R = 0.0545 and wR = 0.0557 for 2048 observed reflections (I > 2s(I)); for BDPM: C24H24N6, Mr = 396.49, monoclinic, C2/c, a = 21.411(3), b = 8.053(1), c = 11.868(1) ? b = 92.63(1)? Z = 4, V = 2044.2(4) 3, Dc = 1.288 g/cm3, m(MoKa) = 0.080 mm-1, F(000) = 840, the final R = 0.0401 and wR = 0.0939 for 1673 observed reflections (I > 2s(I)).

Ultrasonic study on molecular interactions in binary mixtures of formamide with 1-propanol or 2-propanol

Ultrasonic speeds have been measured at 298.15 K and 308.15 K for mixtures of formamide ＋ 1 -propanol or 2-propanol. For an equimolar mixture, excess molar compressibility follows the sequence of l-propanol 〉 2-propanol. The ultrasonic speed data are correlated by various correlations such as Nomoto＇s relation, van Dael＇s mixing relation and impedance dependence relation, and analyzed in terms of Jacobson＇s free length theory and Schaaffs collision factor theory. Excess isentropic compressibility is calculated from ex- perimental ultrasonic speed data and previously reported excess volume data. The excess molar ultrasonic speed and isentropic compressibility values are fitted to Redlich-Kister polynomial equation. Other proper- ties such as molecular association, available volume, free volume, and intermolecular free length are also calculated. The excess isentropic compressibility data are also interpreted in terms of graph theoretical ap- proach. The calculated isentropic compressibility values are well consistent with the experimental data. It is found that the interaction between formamide and propanol increases when hydroxyl group attached to a carbon atom has more -CH3 groups.

Synthesis and Crystal Structure of 2-[(4-Methoxy- 6-methylthio-2-pyrimidinyl)aminocarbonyl- aminosulfonyl] Benzoic Acid Methyl Ester

The title compound 2-[(4-methoxy-6-methylthio-2-pyrimidinyl)aminocarbonyl- aminosulfonyl]benzoic acid methyl ester (C15H16N4O6S2, Mr = 412.44) was obtained by the reaction of (4-methoxy-6-methylthio-2-pyrimidinyl)amine with 2-methoxylcarbonylbenzene-sulfonylisocya- nate. The crystal is of monoclinic, space group P21/c with a =11.169(3), b = 9.508(3), c = 17.690(5) ? b = 91.593(5), Z = 4, V = 1877.9(10) 3, Dc = 1.459 g/cm3, F(000) = 856, m(MoKa) = 0.324 mm-1, R = 0.0690 and wR = 0.1368 for 3301 observed reflections (I > 2s(I)). The N(1)H…N(3) and N(2)H…O(4) hydrogen bonds can be observed. In the molecule the phenyl plane(I), pyrimi- din-2-yl-urea bridge plane(Ⅱ) and ester plane(Ⅲ) form three conjugated systems.

Hydrolysis Kinetics of 2-Pyridinecarboxamide, 3-Pyridinecarboxamide and 4-Pyridinecarboxamide in High-Temperature Water

A kinetic study is reported here on hydrolysis of three pyridinecarboxamides in high-temperature water in the temperature range of 190-250℃ at 8 MPa. 2-Pyridinecarboxamide, 3-pyridinecarboxamide and 4-pyridinecarboxamide hydrolyze to corresponding picolinic acids. 2-Picolinic acid is further decarboxylated to pyridine. Experiments at different temperatures show that the first-order rate constants display an Arrhenius behavior with activation energies of （110.9 ±2.3）, （70.4 ± 2.1） and （61.4 ± 1.8）kJ.mo1-1 for 2- pyridinecarboxamide, 3-pyridinecarboxamide and 4-pyridinecarboxamide, respectively. These kinetic parameters for pyridinecarboxamide hydrolysis are more reliable and accurate than those from the consecutive hydrolysis of cyanopyridines.

Synthesis and characterization of 2-hydroxy-N-methyl-N-phenyl-acetamide

2-hydroxy N methyl N phenyl acetamide was synthesized by using N methylaniline, chloracetyl chloride, anhydrous sodium acetate and methanol through the acetylation, esterfication and ester interchange steps. The acetylation of N methylaniline with chloracetyl chloride, catalyzed by triethylamide with mole ratio n (C 6H 5NHCH 3)∶ n (ClCH 2C(O)Cl)∶ n (N(C 2H 5) 3)=1∶1.05∶1, the yield of 2 chloro N methyl N phenyl acetamide(Ⅰ) was 93.8%; Then the esterification of Ⅰ with anhydrous sodium acetate in the presence of phase transfer catalyst tetrabutyl ammonia bromide gave 97.3% yield of 2 acetoxyl N methyl N phenyl acetamide (Ⅱ); The ester interchange of with methanol catalyzed by potassium hydroxide gave 2 hydroxy N methyl N phenyl acetamide (Ⅲ) in 96.4% yield. And the total yield was 88.0%. IR and MS spectroscopy of products were analyzed and their characteristic peaks were assigned. Combining the results of elemental analysis, the molecular structure of Ⅰ, Ⅱ and Ⅲ was identified.

基于联萘二胺骨架的新型手性硫脲催化剂的合成

以C2轴手性化合物(S)-1,1'-联萘-2,2'-胺和手性氨基醇为原料,经乙酰化、甲基化、水解等反应合成了3种新型的手性硫脲催化剂,其结构经~1H NMR,^(13)C NMR、IR和HR-MS(ESI)表征。

Iron contributes to the formation of catechol isoquinolines and oxidative toxicity induced by overdose dopamine in dopaminergic SH-SY5Y cells

Objective The selective loss of dopaminergic neurons in Parkinson＇s disease is suspected to correlate with the increase of cellular iron, which may be involved in the pathogenesis of PD by promotion of oxidative stress. This research investigated dopamine-induced oxidative stress toxicity contributed by iron and the production of dopamine-derived neurotoxins in dopaminergic SH-SYSY cells. Methods After the SH-SYSY cells were pre-incubated with dopamine and Fe^2＋ for 24 h, the cell viability, hydroxyl radical, melondialdehyde, cell apoptosis, and catechol isoquinolines were measured by lactate dehydrogenase assay, salicylic acid trapping method, thiobarbuteric acid assay, Hoechst 33258 staining and HPLC-electrochemical detection （HPLC-ECD）, respectively. Results （1） Optimal dopamine （150 μmol/L） and Fe^2＋ （40 or 80 μmol/L） significantly increased the concentrations of hydroxy radicals and melondialdehyde in SH-SYSY cells. （2） Induction with dopamine alone or dopamine and Fe^2＋ （dopamine/Fe^2＋） caused cell apoptosis. （3） Compared with untreated cells, the catechol isoquinolines, salsolinol and N-methyl-salsolinol in dopamine/Fe^2＋-induced cells were detected in increasing amounts. Conclusion Due to dopamine/Fe^2＋-induced oxidative stress similar to the state in the parkinsonian substantia nigra neurons, dopamine and Fe^2＋ impaired SH-SYSY cells could be used as the cell oxidative stress model of Parkinson＇s disease. The catechol isoquinolines detected in cells may be involved in the pathogenesis of Parkinson＇s disease as potential neurotoxins.

Nicotinamide overload may play a role in the development of type 2 diabetes

AIM： To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS： Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N^1-methylnicotinamide on glucose metabolism, plasma HzO2 levels and tissue nicotinamide adenine dinucleotide （NAD） contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS： Diabetic subjects had significantly higher plasma N^1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects （0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P 〈 0.001）. Cumulative doses of nicotinamide （2 g/kg） significantly increased rat plasma Nl-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by Nl-methy-Inicotinamide. Moreover, cumulative exposure to N^1- methylnicotinamide （2 g/kg） markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N^1-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide （5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load）. Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N^1- methylnicotinamide clearance. CONCLUSION： These findings suggest that nicotinamide overload, which induced an increase in plasma N^1- methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.