1-[2-(2,4-二氯苯基)-4-烃氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑类化合物的合成及杀菌活性研究

2,4-二氯苯乙酮经溴化得ω-溴-2,4-二氯苯乙酮,该化合物与丙三醇在对甲基苯磺酸催化下脱水,得2-(2,4-二氯苯基)-2-溴甲基-4-羟甲基-1,3-二氧戊环,该中间体与苯甲酰氯在常温下反应,合成了2-(2,4-二氯苯基)-2-溴甲基-4-苯甲酰氧基甲基-1,3-二氧戊环,然后与三氮唑钠盐在130℃反应36 h,之后在碱性条件下水解,获得1-[2-(2,4-二氯苯基)-4-羟甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑,再以吡啶为缚酸剂继续与甲磺酰氯反应,合成了1-[2-(2,4-二氯苯基)-4-甲磺酰氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑,最后在碱性条件下,与12个不同结构的酚缩合成标题化合物1-[2-(2,4-二氯苯基)-4-烃氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑。标题化合物的结构用GC-MS、FTIR进行了表证。生物活性实验结果表明,12个标题化合物对水稻稻瘟病菌的抑菌率均在88.0%以上,其中,1-[2-(2,4-二氯苯基)-4-间甲基苯氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑达100%。1-[2-(2,4-二氯苯基)-4-苯氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑和1-[2-(2,4-二氯苯基)-4-对硝基苯氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑对油菜菌核病菌的抑菌率分别为100%和97.8%;1-[2-(2,4-二氯苯基)-4-间甲基苯氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑对小麦赤霉病菌的抑制活性为91.2%。     

1-[2-(2,4-二氯苯基)-4-酰氧基甲基-1,3-二氧戊环-2-基]甲基-1H-1,2,4-三氮唑的合成及生物活性

2, 4 二氯苯乙酮经溴化得ω 溴 2, 4 二氯苯乙酮,该化合物与丙三醇反应并脱水得 2 (2, 4 二氯苯基 ) 2 溴甲基 4 羟甲基 1, 3 二氧戊环,再在常温下与苯甲酰氯反应合成 2 (2, 4 二氯苯基) 2 溴甲基 4 苯甲酰氧基甲基 1, 3 二氧戊环,然后在 130℃与 1H 1, 2, 4 三唑钠反应 36h,所得产物经水解得 1 [2 (2, 4 二氯苯基 ) 4 羟甲基 1, 3 二氧戊环 2 基]甲基 1H 1, 2, 4 三氮唑,再在室温以吡啶作缚酸剂,与甲磺酰氯反应 20h,合成 1 [2 (2, 4 二氯苯基) 4 甲磺酰氧基甲基 1, 3 二氧戊环 2 基]甲基 1H 1, 2, 4 三氮唑,最后与各类羧酸的钾盐反应,合成了 10种 1 [2 (2, 4 二氯苯基 ) 4 酰氧基甲基 1, 3 二氧戊环 2 基 ]甲基 1H 1, 2, 4 三氮唑类化合物。产物的结构经GC MS、IR证实。对目标产物进行了杀菌活性测定,结果表明,各化合物均具有不同程度的生物活性,其中: 1 [2 (2, 4 二氯苯基) 4 (α 甲基苯乙酰氧基)甲基 1, 3 二氧戊环 2 基]甲基 1H 1, 2, 4 三氮唑对水稻稻瘟病菌和油菜菌核病菌的抑制率,分别达到 92 1%与 95 6%,对小麦赤霉病菌和瓜类灰霉病菌的抑制率达到 80%以上;1 [2 (2, 4 二氯苯基) 4 对氟苯甲酰氧基甲基 1, 3 二氧戊环 2 基 ]甲基 1H 1, 2, 4 三氮唑对水稻稻瘟病菌和油菜菌核病菌的抑制率分别为 9     

2,7-二氮杂-螺[3,5]壬烷-2-甲酸叔丁酯的合成

报道了2,7-二氮杂-螺[3,5]壬烷-2-甲酸叔丁酯一种新的合成方法。以双(2-氯乙基)胺盐酸盐(■)为起始原料,经氮苄基化后与氰乙酸乙酯双烷基化生成4,4-双取代的N-苄基哌啶(■),哌啶甲酸乙酸酯(■)经硼氢化钠还原成羟基化合物(■),随后对甲苯磺酰化成磺酸酯(■),氰基经氢化铝锂还原后发生分子内协同反应环化成2-氮杂螺环丁烷(■),经与二碳酸叔丁酯反应生成2-N-Boc产物(■),最后氢解脱去苄基等7步反应得到标题化合物2,7-二氮杂-螺[3,5]壬烷-2-甲酸叔丁酯,总收率为36%,~1H NMR和MS确证了中间体和目标产物结构。     

(R)-(+)-2,2’-双[二(3,5-二甲苯基)膦]-1,1’-联萘的合成

三溴化磷为原料,与二(3,5-二甲基苯基)氧化膦反应,得到二(3,5-二甲基苯基)溴化膦,通过催化偶联反应,得到(R)-(+)-2,2’-双[二(3,5-二甲苯基)膦]-1,1’-联萘。通过考察各步的反应条件,得出最佳的工艺条件,(R)-(+)-2,2’-双[二(3,5-二甲苯基)膦]-1,1’-联萘的收率可达67%,e.e.值为99.2%。     

(R)-(+)-2,2’-双[二(3,5-二甲苯基)膦]-1,1’-联萘的合成

三溴化磷为原料,与二(3,5-二甲基苯基)氧化膦反应,得到二(3,5-二甲基苯基)溴化膦,通过催化偶联反应,得到(R)-(+)-2,2’-双[二(3,5-二甲苯基)膦]-1,1’-联萘。通过考察各步的反应条件,得出最佳的工艺条件,(R)-(+)-2,2’-双[二(3,5-二甲苯基)膦]-1,1’-联萘的收率可达67%,e.e.值为99.2%。     

微波辐射下4-氨基-3,5-二羟甲基-1,2,4-三唑的合成

以羟基乙酸,一水合肼为原料,在微波辐射下合成了多齿配体4-氨基-3,5-二羟甲基-1,2,4-三唑。讨论了微波反应时间、微波功率、原料配比对4-氨基-3,5-二羟甲基-1,2,4-三唑收率的影响,得到最优条件;微波反应时间90 min,微波功率480 W,一水合肼/羟基乙酸=1.5/1。新的合成方法使反应时间由文献报道的24 h缩至90 min,缩合反应的收率由文献报道的58%提高到78%。     

5-甲基胞嘧啶的合成

5-甲基胞嘧啶是一个非常重要的医药中间体,用来制备抗病毒和抗肿瘤等药物。以5-甲基脲嘧啶为原料,先与三氮唑反应制得中间体5-甲基-4-(1,2,4-三氮唑)-嘧啶-2-酮,接着该中间体在浓氨水的作用下水解生成最终产物5-甲基胞嘧啶,总收率为24.4%。     

3,5-双三氟甲基苯甲酸的合成研究

3,5-双三氟甲基苯甲酸[CAS:725-89-3]的合成是先通过1,3-二溴-5,5-二甲基乙内酰脲,与1,3-双三氟甲基苯生成3,5-双三氟甲基溴苯,收率98%,选择性99%.然后由3,5-双三氟甲基溴苯作原料来合成3,5-双三氟甲基苯甲酸,收率72%以上.本文讨论了不同反应摩尔比,反应温度等条件,并得到最优化条件.     

阿巴卡韦中间体2-杂氮双环[2,2,1]庚-5-烯-3-酮的合成

采用一步法由对甲基苯亚磺酸钠与氯化氰及1,3-环戊二烯合成目标物2-杂氮双环[2,2,1]庚-5-烯-3-酮。反应条件为:n(对甲基苯亚磺酸钠)∶n(氯化氰)∶n(1,3-环戊二烯)=0.48∶1.05∶1,反应温度控制在15℃,反应7h,反应中控制pH=5,可得纯度为95%的产品,收率由文献报道的64%提高到78%。     

8-(3-氯苯基)-3-甲硫基-1-苯基-吡唑并[3,4-d][1,2,4]三唑并[1,5-a]嘧啶-4-酮衍生物的合成与表征

以吡唑膦亚胺、3-氯苯基异氰酸酯和取代苯氧乙(丙)酰肼为原料,通过串联氮杂Wittig关环反应合成了6个未见文献报道的化合物8-(3-氯苯基)-3-甲硫基-1-苯基-吡唑并[3,4-d][1,2,4]三唑并[1,5-a]嘧啶-4-酮衍生物((1)a～(1)f),通过核磁共振氢碳谱和HRMS等确证进行了表征.     

Five co-ordination at platinum(II) in a water soluble tertiary phosphine complex: crystal structure of [Pt(PTA)3(I)2]·CH3OH

A five co-ordinate platinum(II) complex containing the water soluble 1,3,5-triaza-7-phosphaadamantane ligand (PTA) [Pt(PTA)₃(I)₂] (1), was characterised in the solid state and aqueous solution. A re-calculation of the Tolman cone angle for the PTA ligand, as well as preliminary equilibrium constants for the formation of 1, is given.     

In situ NMR characterisation of an intermediate in the catalytic hydrogenation of CO2 and HCO3- in aqueous solution

The water soluble ruthenium(II) complex [RuCl₂(PTA)([9]aneS₃)] (PTA = 1,3,5-triaza-7-phosphadamantane, [9]aneS₃ = 1,4,7-trithiacyclononane) catalyzes the hydrogenation of CO₂ and bicarbonate in aqueous solution. While the catalytic activity is low, the formation of an intermediate involving coordination of both hydride and bicarbonate to the ruthenium centre has been unambiguously established by ¹H, ³¹P and ¹³C NMR spectroscopy. Such an intermediate has previously been proposed on the basis of theoretical studies and experimental findings.     

Ruthenium-catalyzed reduction of allylic alcohols using glycerol as solvent and hydrogen donor

Glycerol, a biodegradable and virtually non-toxic chemical, can be used as a green solvent and hydrogen donor in the ruthenium-catalyzed reduction of allylic alcohols, a tandem process that involves the initial redox-isomerization of the allylic alcohol and subsequent transfer hydrogenation of the resulting carbonyl compound. Among the different ruthenium sources employed, the best results were obtained with the hydrophilic arene–Ru(II) complex [RuCl₂(η⁶-C₆H₆)(DAPTA)] (DAPTA = 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane), which associated with KOH generates the corresponding saturated alcohols in high yields (up to 90%) and with almost complete selectivity in short reaction times. Interestingly, these reduction processes are also operative using technical grade glycerol.     

GLYCEROL CONDENSATION PRODUCTS OF AMINOANTHRAQUINONES

Glycerol condensation reaction of 2- and 1-aminoanthraquinones was reexamined. 2-Aminoanthraquinone gave phenaleno[3,2-f]quinolin-7-one (10,11-pyridinobenzanthrone), 9H- phenanthro[10,1-gh]quinolin-9-one (4,5-pyridinobenzanthrone) and phenaleno[2,3-g]quinolin-7-one (10,9-pyridinobenzanthrone) besides phenaleno[2,3-f]quinolin-13-one (9,8-pyridinobenzanthrone) hitherto reported. 1-Aminoanthraquinone gave phenaleno[3,2-h]quinolin-13-one (8,9-pyridinobenzanthrone) along with a small amount of phenaleno[2,3-h]quinolin-7-one (11,10-pyridinobenzanthrone), but not 13H-phenanthro[1,10-gh]quinolin-13-one (6,5-pyridinobenzanthrone) as hitherto reported. NMR spectra of these six compounds were assigned and they supported the assigned isomeric structures.     

Altered DNA Binding and Amplification of Human Breast Cancer Suppressor Gene BRCA1 Induced by a Novel Antitumor Compound, [Ru(��6-p-phenylethacrynate)Cl2(pta)]

The ruthenium-based complex [Ru(η⁶-p-phenylethacrynate)Cl₂(pta)] (pta = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane), termed ethaRAPTA, is an interesting antitumor compound. The elucidation of the molecular mechanism of drug activity is central to the drug development program. To this end, we have characterized the ethaRAPTA interaction with DNA, including probing the sequence specific modified DNA structural stability and DNA amplification using the breast cancer suppressor gene 1 (BRCA1) of human breast and colon adenocarcinoma cell lines as models. The preference of ethaRAPTA base binding is in the order A > G > T > C. Once modified, the ethaRAPTA-induced BRCA1 structure has higher thermal stability than the modified equivalents of its related compound, RAPTA-C. EthaRAPTA exhibits a higher efficiency than RAPTA-C in inhibiting BRCA1 amplification. With respect to both compounds, the inhibition of BRCA1 amplification is more effective in an isolated system than in cell lines. These data provide evidence that will help to understand the process of elucidating the pathways involved in the response induced by ethaRAPTA.     

Cyclodextrins as first and second sphere ligands for Rh(I) complexes of lower-rim PTA derivatives for use as catalysts in aqueous phase hydrogenation

The rhodium complex [Rh(cod)Cl(N-tBuBzPTA)]PF₆ (2) was obtained by reacting the appropriate Rh(I) precursor with the lower-rim PTA derivative [N-tBuBzPTA]PF₆ (tBuBz = 4-tert-butylbenzyl; PTA = 1,3,5-triaza-7-phosphaadamantane). The solubility and stability in water of 2 were increased in the presence of native-β-cyclodextrin (β-CD). The interaction of 2 with mono-amino β-cyclodextrin (β-CDNH₂, 2 equiv.) led to a supramolecular Rh assembly (3), identified by ³¹P, ¹H and 2D T-ROESY NMR experiments. The catalytic activity of 3 was evaluated in the water-phase hydrogenation of unsaturated and allylic alcohols and preliminary results are presented here.     

IDENTIFICATION OF THE C30H16 POLYCYCLIC AROMATIC HYDROCARBON BENZO[cd]NAPHTHO[1,2,3-lm]PERYLENE AS A PRODUCT OF THE SUPERCRITICAL PYROLYSIS OF A SYNTHETIC JET FUEL

Using high-pressure liquid chromatography (HPLC) with ultraviolet-visible (UV) diode-array and mass spectrometric detection, we have analyzed the products of a Fischer-Tropsch synthetic jet fuel pyrolyzed, under supercritical conditions, at 710°C and 42 atm. An eight-ring polycyclic aromatic hydrocarbon, benzo[cd]naphtho[1,2,3-lm]perylene, has been unequivocally identified among the product components by its characteristic ultraviolet-visible absorbance spectrum. First, the unknown product component's HPLC elution behavior and UV absorbance characteristics indicated that it was a planar benzologue of dibenzo[cd,lm]perylene, having a high length-to-breadth ratio. Next, the mass spectrum established the isomer family of the unknown compound as C₃₀H₁₆. The UV absorption spectrum was then progressively analyzed with different solvents to achieve the final identification of benzo[cd]naphtho[1,2,3-lm]perylene. Benzo[cd]naphtho[1,2,3-lm]perylene has never before been reported as a product in any combustion or pyrolysis study.     

SEPARATION OF AROMATIC AND ALIPHATIC HYDROCARBONS WITH IONIC LIQUIDS

Naphtha cracker feeds may contain 10-25 wt% aromatic compounds. Removal of these aromatic compounds from the feed to the cracker would offer several advantages: higher capacity, higher thermal efficiency, and less coke formation. In this work, we investigated the separation of toluene from heptane by extraction with ionic liquids.

Several ionic liquids are suitable for extraction of toluene from toluene/heptane mixtures. The selectivities for the aromatic/aliphatic hydrocarbon separation with all ionic liquids tested increase with decreasing aromatic content in the feed. The toluene/heptane selectivities at 10% toluene in the feed at T = 40°C and 75°C with several ionic liquids ([emim]HSO₄, [mmim] methylsulfate, [emim] ethylsulfate, [bmim]BF₄, [emim] tosylate, [mebupy]BF₄, and [mebupy] methylsulfate) are a factor of 1.5-2.5 higher than those obtained with sulfolane, which is a conventional solvent for the extraction of aromatic hydrocarbons from a mixed aromatic/aliphatic hydrocarbon stream. The three most suitable ionic liquids from the ionic liquids tested for the separation of aromatic and aliphatic hydrocarbons are [mebupy]BF₄, [mebupy]CH₃SO₄, and [bmim]BF₄ and at 75°C also [emim] tosylate. The ionic liquid [mebupy]BF₄ is selected for further testing in our extraction pilot plant.

Because ionic liquids have a negligible vapor pressure, evaporating the extracted hydrocarbons from the ionic liquid phase could achieve the recovery of the ionic liquid. A conceptual process scheme for the extraction has been set up. Preliminary calculations show that both the investment costs and the energy costs will be considerably lower with ionic liquids than with sulfolane as the solvent.     

SEPARATION OF AROMATIC AND ALIPHATIC HYDROCARBONS WITH IONIC LIQUIDS

Naphtha cracker feeds may contain 10–25 wt% aromatic compounds. Removal of these aromatic compounds from the feed to the cracker would offer several advantages: higher capacity, higher thermal efficiency, and less coke formation. In this work, we investigated the separation of toluene from heptane by extraction with ionic liquids.

Several ionic liquids are suitable for extraction of toluene from toluene/heptane mixtures. The selectivities for the aromatic/aliphatic hydrocarbon separation with all ionic liquids tested increase with decreasing aromatic content in the feed. The toluene/heptane selectivities at 10% toluene in the feed at T = 40°C and 75°C with several ionic liquids ([emim]HSO₄, [mmim] methylsulfate, [emim] ethylsulfate, [bmim]BF₄, [emim] tosylate, [mebupy]BF₄, and [mebupy] methylsulfate) are a factor of 1.5–2.5 higher than those obtained with sulfolane, which is a conventional solvent for the extraction of aromatic hydrocarbons from a mixed aromatic/aliphatic hydrocarbon stream. The three most suitable ionic liquids from the ionic liquids tested for the separation of aromatic and aliphatic hydrocarbons are [mebupy]BF₄, [mebupy]CH₃SO₄, and [bmim]BF₄ and at 75°C also [emim] tosylate. The ionic liquid [mebupy]BF₄ is selected for further testing in our extraction pilot plant.

Because ionic liquids have a negligible vapor pressure, evaporating the extracted hydrocarbons from the ionic liquid phase could achieve the recovery of the ionic liquid. A conceptual process scheme for the extraction has been set up. Preliminary calculations show that both the investment costs and the energy costs will be considerably lower with ionic liquids than with sulfolane as the solvent.     

试验高炉内硅锰的还原

在0．10m3试验高炉内进行了含碳球团还原的热态试验，冶炼出12％Si、45％Mn的硅锰铁合金.作者在理论分析的基础上，讨论了Si-Mn耦合反应，研究了金属熔体中的脱硫能力实验表明：（1）温度是影响Si、Mn还原的关键，炉渣碱度应控制在1．2－1．4范围内；（2）S随[Si]、[Mn]的增加逐渐下降，可以较易将[S]控制在0．02％以下，最低的硫含量为0．0024％；（3）[P]的大小主要取决于原料带入的磷含量，约为0．30％，并且波动不大．