Synthesis and Crystal Structure of a Novel Ethyl 5-(4-(2-Phenylacetamido)phenyl)-1H-pyrazole-3-carboxylate as an Acrosin Inhibitor

The title compound （ethyl5-（4-（2-phenylacetamido）phenyl）-lH-pyrazole-3-carboxylate, C20H19N3O3） was synthesized by the reaction of Claisen condensation, cyclization, reduction and acylation. The structure was characterized by X-ray diffraction, MS, NMR and IR. It belongs to the monoclinic system, space group C2/c with a = 22.723（9）, b = 9.324（4）, c = 18.890（8） A, β = 114.259（6）°, V = 3649（3） A^3, Dc = 1.272 Mg·m^3, Z = 8, Mr = 349.38, p = 0.087 mm^-1, F（000） = 1472, the final R = 0.0615 and wR = 0.1643. The biological test shows that the title compound has a moderate acrosin inhibition activity.

Synthesis, Bioactivity, and Crystal Structure Analysis of 2-(3-Oxobenzo[d]isothiazol-2(3H)-yl)ethyl Benzoates

Fifteen novel 2-（3-oxobenzo[d]isothiazol-2（3H）-yl）ethyl benzoates were synthesi- zed by the condensation of 2-（2-hydroxyethyl）benzo[d]isothiazol-3（2H）-one with substituted benzoic acids in dichloromethane. All the compounds were characterized by elemental analysis, IR, ESI-MS and 1H NMR. The crystal structures for 2-（2-hydroxyethyl）benzo[d]isothiazol-3（2H）-one （2） and 2-（3-oxobenzo[d]isothiazol-2（3H）-yl）ethyl 2-methoxybenzoate （30） have been determined by X-ray crystal structure analysis. Compound 2 （C9H9NO2S） crystallizes in the monoclinic system, space group Pn with a = 10.552（3）, b = 7.849（2）, c = 10.765（4） A, β = 103.128（4）°, V= 868.3（5） A3, Mr = 195.24, Dc = 1.493 Mg.m-3, μ = 0.33 mm-1, F（000） = 408, Z = 4, R= 0.0314 and wR= 0.0628. Compound 30 （C17H15NO4S） crystallizes in the triclinic system, space group P1 with a = 8.028（2）, b = 9.300（2）, c = 10.430（3）A, V= 752.1（3）A3, Mr = 329.36, D,= 1.454 Mg.m-3, p = 0.24 mm-1, F（000） = 344, Z = 2, R = 0.0377 and wR = 0.0904. The preliminary biological test indicated that the title compounds show better growth inhibitory activity against the gram-positive bacteria than the gram-negative bacteria.

Long-term and combined effects of N-[2-(nitrooxy)ethyl]-3-pyridinecarboxamide and fumaric acid on methane production,rumen fermentation, and lactation performance in dairy goats

Background:In recent years,nitrooxy compounds have been identified as promising inhibitors of methanogenesis in ruminants.However,when animals receive a nitrooxy compound,a high portion of the spared hydrogen is eructated as gas,which partly offsets the energy savings of CH4mitigation.The objective of the present study was to evaluate the long-term and combined effects of supplementation with N-[2-(nitrooxy)ethyl]-3-pyridinecarboxamide(NPD),a methanogenesis inhibitor,and fumaric acid(FUM),a hydrogen sink,on enteric CH4production,rumen fermentation,bacterial populations,apparent nutrient digestibility,and lactation performance of dairy goats.Results:Twenty-four primiparous dairy goats were used in a randomized complete block design with a 2×2factorial arrangement of treatments:supplementation without or with FUM(32 g/d)or NPD(0.5 g/d).All samples were collected every 3 weeks during a 12-week feeding experiment.Both FUM and NPD supplementation persistently inhibited CH4yield(L/kg DMI,by 18.8%and 18.1%,respectively)without negative influence on DMI or apparent nutrient digestibility.When supplemented in combination,no additive CH4suppression was observed.FUM showed greater responses in increasing the molar proportion of propionate when supplemented with NPD than supplemented alone(by 10.2%vs.4.4%).The rumen microbiota structure in the animals receiving FUM was different from that of the other animals,particularly changed the structure of phylum Firmicutes.Daily milk production and serum total antioxidant capacity were improved by NPD,but the contents of milk fat and protein were decreased,probably due to the bioactivity of absorbed NPD on body metabolism.Conclusions:Supplementing NPD and FUM in combination is a promising way to persistently inhibit CH4emissions with a higher rumen propionate proportion.However,the side effects of this nitrooxy compound on animals and its residues in animal products need further evaluation before it can be used as an animal feed additive.

Synthesis and Crystal Structure of Ethyl 3-(4-Chlorophenyl)-3,4-dihydro-6-methyl-4-oxo-2-(pyrrolidin-1-yl)furo[2,3-d]pyrimidine-5-carboxylate

The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215（9）, b = 8.5311（4）, c = 21.6886（9） A^°, β = 91.607（1）°, V = 3814.0（3）A^°^3, Z = 8, Dc = 1.400 g/cm^3, F（000） = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.

Synthesis, Crystal Structure and Antitumor Activities of N-(2-(1H-indol-3-yl)ethyl)-2-nitroaniline

The title compound, N-(2-(1H-indol-3-yl)ethyl)-2-nitroaniline(C16H15N3O2, Mr = 281.31), has been synthesized by the multicomponent reaction of milder Ullmann, and its structure was characterized by 1H NMR, 13 C NMR, IR, H RMS(ESI) and single-crystal X-ray diffraction. It crystallizes in monoclinic, space group I2/c with a = 15.0212(10), b = 9.4911(6), c = 20.3075(13) A, β = 100.776(7)o, V = 2844.1(3)A3, Z = 8, Dc = 1.314 g/cm3, F(000) = 1184.0, μ = 0.089 mm-1, the final R = 0.0574 and w R = 0.1688 for 1701 observed reflections(I 】 2σ(I)). X-ray analysis indicates three major N(2)–H(2)···O(2), C(13)–H(13)···O(2), N(2)–H(2)···N(3) hydrogen bonds and π-π stacking interactions in the crystal structure. The preliminary biological test shows that the title compound has a good antitumor activity against A549 in vitro with the IC50 value of 35 μmol/L.

An Alternative Synthesis and Crystal Structure Characterization of Nutrient Fortifier N-(1-(Phenylacetyl)-L-prolyl) Glycine Ethyl Ester

A nutritional fortifier N-(1-(phenylacetyl)-L-prolyl)glycine ethyl ester(4)was successfully synthesized through two synthetic schemes and characterized by IR,^1H-NMR,^13C-NMR,elemental analysis and X-ray single-crystal diffraction.The intermediate N-phenylacetyl-L-proline(2)was synthesized by the solid-liquid reaction of L-proline and phenylacetyl chloride directly.Compound 2(C13 H15 NO3,Mr=233.26)belongs to the orthorhombic system,space group P212121 with a=8.9468(3),b=9.3190(3),c=14.0453(4)A,V=1171.03(6)A^3,Z=4,Dc=1.323 g/cm^3,μ=0.773 mm^-1,F(000)=496.0,the final R=0.0313 and wR=0.0797 for all data.Compound 4(C17 H22 N2 O4,Mr=318.36)is of orthorhombic system,space group P212121 with a=6.5831(2),b=8.5536(2),c=28.9138(9)A,V=1628.11(8)A^3,Z=4,Dc=1.299 g/cm3,μ=0.763 mm-1,F(000)=680.0,the final R=0.0353 and wR=0.0816 for all data.

Synthesis and Crystal Structure of 4-(4,6-Dimethoxylpyrimidin-2-yl)-3-thiourea Carboxylic Acid Ethyl Ester

4-（4,6-Dimethoxyl-pyrimidin-2-yl）-3-thiourea carboxylic acid ethyl ester was synthesized by the reaction of 2-amino-4,6-dimethoxyl pyrimidine, potassium thiocyanate and methyl chloroformate in ethyl acetate. Single crystals suitable for X-ray measurement were obtained by recrystallization with the solvent of dimethyl formamide at room temperature. The crystal structure was determined by X-ray diffraction analysis. Crystallographic data： C10H14N4O4S, M, = 286.31, monoclinic, space group C2/c with a = 2.5309（3）, b = 0.67682（6）, c = 1.74237（19） nm, β = 114.744（3）°, V= 2.7106（5） nm3, Dc = 1.403 g/cm3, p = 0.225 mm-1, F（000） = 1200, Z= 8, R= 0.0514 and wR= 0.1529.

Identification of N-Methyl Bis(2-(Alkyloxy-Alkylphosphoryloxy)Ethyl) Amines by LC-HRMS/MS

N-Methyl bis(2-(alkyloxy-alkylphosphoryloxy)ethyl)amines, which are abbreviated as PNPs, are a series of new skeleton chemicals belonging to schedule 2.B.04 chemicals of Chemical Weapons Convention (CWC). PNPs are important markers of chemical warfare agents because they are structurally relative to both nerve agents and N-mustards. In this study, fragmentation pathways of the most characteristic fragment ions in Q-TOF mass spectrometry were proposed based on the information from accurate mass and secondary fragmentations of product ions scan experiments. Results indicated that the base ion in LC/HRMS was the quasi-molecular ion [M+H]+. In LC-HRMS/MS, it was [M+H-CnH2n+1P(O)(OH)CmH2m+1O]+ fragment ion which was formed by losing an alkyloxy alkylphosphoryloxy group from the quasi-molecular ion. The diagnostic ion m/z84.0814 was identified as [C5H10N]+, which was the group of (CH2=CH)2N+(H)CH3. PNPs have two protonated centers. One is on the N atom, the other is on the O atom (P=O). O-n-propyl PNPs generally exhibited two fragmentation pathways. Firstly, the quasi-molecular ion [M+H]+ lost a propoxy alkylphosphoryloxy group to produce [R1P(OH+)(O-n-C3H7)OCH2CH2N(CH3)CH=CH2]+, which could be fragmented further to produce [C5H10N]+ ion. Secondly, [R1P(OH+)(O-n-C3H7) OCH=CH2]+ ions were produced from [M+H]+ and fragmented further to produce the abundant ions [R1P(OH+)(OH)OCH =CH2]. However, O-isopropyl PNPs characteristically produced weak fragment ions [M+H-C3H6]+, which were presumably formed via loss of CH3CH=CH2 from [M+H]+. Other PNPs showed similar fragmentation pathways as O-n-propyl PNPs. On the summarization of the MS fragmentation pathways of PNPs, LC-HRMS/MS quantitative and qualitative methods were developed and applied to analyze N-Methyl bis(2-(butoxy-methylphosphoryloxy)ethyl]amine in high background organic samples. The analytical results had successfully supported the sample preparation for the 33rd official proficiency test of Organization for Prohibition of Chemical Weapons (OPCW).

Synthesis of Temperature- and pH-Sensitive Graft Copolymer Containing 2-(Diethylamino)ethyl Methacrylate and N-Vinylcaprolactam onto Silicone Rubber

Silicone rubber films were modified by the consecutive grafting of 2-(diethylamino)ethyl methacrylate (DEAEMA) and N-vinylcaprolactam (NVCL) using direct method on two steps with gamma-rays. The effect of absorbed dose and monomer concentration on grafting degree was determined. The grafted samples were verified by FTIR-ATR spectroscopy and swelling;thermal properties were analyzed by DSC and TGA. The stimuli-responsive behavior was studied by swelling and/or DSC. Thermo- and pH-sensitive films of (PP-g-DEAEMA)-g-NVCL presented a pH critical at 3.2 and LCST around 63.5℃.

Synthesis and Crystal Structure of Ethyl 2-(6-(1,3-Dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) Butanoate

The title compound ethyl 2-（6-（1,3-dioxo-4,5,6,7-tetrahydro-lH-isoindol-2（3H）- yl）-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4（3H）-yl） butanoate 3 was synthesized by the reaction of ethyl 2-（6-amino-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4（3H）-yl） butanoate with 4,5,6,7- tetraydrophthalic anhydride, and its structure was determined by X-ray single-crystal diffraction. The crystal belongs to the monoclinic system, space group P2 1/n with a = 9.3469（2）, b = 16.7715（5）, c = 13.7153（4） A, β= 104.9680（10）°, μ = 0.107 mm^-1, Mr = 430.42, V= 2077.08（10） ,A3, Z= 4, Dc = 1.376 g/cm3, F（000） = 904, T= 296（2） K, R = 0.0508 and wR = 0.1478.

高效液相色谱-质谱法检测水稻中吡嘧磺隆残留量方法研究

本文采用液相色谱-质谱联用快速分析方法,来检测吡嘧磺隆在水稻植株、土壤残留动态,探究液相色谱-质谱的灵敏度、准确度和可靠性。本文采用Qu ECHERS方法进行样品快速前处理,样品经乙腈提取,PSA、C18吸附剂净化,C18色谱柱分离,0.2%甲酸水∶乙腈等度洗脱,质谱采用电喷雾正离子(ESI+)模式电离,多反应离子监测模式定性分析,基质标匹配外标法定量。在0.02~0.1mg/kg浓度范围内,在不同基质中的吡嘧磺隆的线性相关系数均>0.990 7。在3个浓度添加水平范围内,土壤、水稻植株、稻壳和糙米样品中吡嘧磺隆的平均回收率在78.4%~100.3%之间,相对偏差为1.80%~14.9%。该方法简单、快速、灵敏度高、准确度好,能够满足水稻及土壤中吡嘧磺隆残留量的检测要求。

HPLC法检测6%吡嘧磺隆·丙草胺·二氯喹啉酸颗粒剂

采用高效液相色谱法,使用50 mm×4.6 mm C_(18)色谱柱,以甲醇+乙腈+0.05%磷酸水溶液为流动相,在254 nm(2 min后更改为230 nm)波长下对吡嘧磺隆·丙草胺·二氯喹啉酸颗粒剂进行分离和检测。经检测二氯喹啉酸、吡嘧磺隆、丙草胺在此分析方法下具有良好的线性关系。吡嘧磺隆线性回归方程为y=3144x+2.8726,相关系数R^(2)=0.9999。丙草胺线性回归方程为y=426.78x-0.08,相关系数R^(2)=0.9994。二氯喹啉酸线性回归方程为y=5630.4x+51.736,相关系数R^(2)=1.0000。此检测方法具有线性关系好、精密度高、回收率高、检测速度快的特点,适用于该产品的定性定量检测。

高效液相色谱-串联质谱法检测稻田中吡嘧磺隆和苯噻酰草胺残留

采用高效液相色谱-串联质谱法（HPLC-MS/MS）,建立了稻田水、土壤、水稻植株、稻秆、稻壳及糙米基质中吡嘧磺隆和苯噻酰草胺的残留分析方法。样品经20 m L V（乙腈）∶V（水）=70∶30的混合溶液提取,提取液用20 mg石墨化碳黑（GCB）与30 mg乙二氨基-N-丙基硅烷（PSA）净化,HPLC-M S/M S检测。吡嘧磺隆在上述各基质中的添加回收率在76%~107%之间,相对标准偏差（RSD）在1.5%~14%之间,定量限为0.004~0.01 mg/kg;苯噻酰草胺的添加回收率在77%~101%之间,RSD在2.4%~13%之间,定量限为0.001~0.01 mg/kg。实现了对两种除草剂同时简便、快速测定的要求。采用该方法测定了26%吡嘧磺隆·苯噻酰草胺水面扩展粒剂在稻田施用后,其有效成分吡嘧磺隆和苯噻酰草胺在实际样品中的残留量。结果表明,两种除草剂均属于易降解农药,在本试验条件下其在糙米中的残留量均低于我国最大残留限量（MRL）（吡嘧磺隆0.1 mg/kg;苯噻酰草胺0.05 mg/kg）。

农产品中百速隆残留量的液相色谱-质谱法测定

建立了农产品中除草剂百速隆残留量的液相色谱-质谱（GC/MS）检测方法;样品经溶剂提取、固相萃取柱净化,采用液质联用仪在选择离子监测模式下进行快速定性定量分析,外标法定量,方法检出限为0.01 mg/kg。在大米、苹果、洋葱、猪肝中4种样品中添加不同浓度的百速隆时,其平均添加回收率在78.9%-95.9%之间,相对标准偏差（n=10）为2.1%-8.4%。

高效液相色谱-串联质谱法检测水稻中吡嘧磺隆残留

采用高效液相色谱-串联质谱法,建立了吡嘧磺隆在稻田水、土壤、动态植株、稻秆、稻壳、稻米等6种基质中的残留检测方法。样品采用乙腈提取,C18净化,HPLC-MS/MS检测。结果表明,吡嘧磺隆在上述6种基质中的添加回收率在77.7%~105.0%之间,相对标准偏差在0.9%~7.0%之间,定量限(LOQ)为0.001~0.01 mg/kg。方法符合农药残留检测要求。

Synthesis of Agomelatine by One-pot Catalytic Hydrogenation and Acetylation with NiO

Nano-NiO and bulk NiO were prepared from Ni(AC)_2·4 H_2O by coordination precipitation using aqueous ammonia and by a solid state reaction, respectively. The nickel oxide particles were characterized by X-ray Diffraction(XRD) and scanning electron microscopy(SEM). The results indicate that nano-sized NiO has a crystal phase with a standard face-centered cubic lattice structure, with a mean particle diameter of about 10 nm. The evaluation of the activity of nickel oxide nanoparticles in the catalytic hydrogenation of 7-methoxy-1-naphthylacetonitrile was carried out. The results demonstrate the efficient synthesis of the title compound by a one-pot catalytic hydrogenation and acetylation with NiO. The NiO nanoparticles displayed superior catalytic activity in the synthesis of agomelatine in the one-pot reaction.The total yield of agomelatine is over 81.8% with a purity of 99.2%, as determined by HPLC. The structure of agomelatine was confirmed by IR, MS, and 1 H NMR analysis.

A Facile Synthesis of 9,10-Dimethoxybenzo[6,7]- ox-epino[3,4-<i>b</i>]quinolin-13(6<i>H</i>)-one and Its Derivatives

A concise and efficient method for the synthesis of novel 9,10-imethoxybenzo[6,7]oxepino[3,4-b]quinolin13(6H)-one and its derivatives 7a-p has been developed via the intramolecular Friedel-Crafts acylation reactions of 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylic acids 6a-p with polyphosphoric acid (PPA) as catalyst and solvent under mild conditions. The key intermediates 6a-p were prepared through the in situ formation of ethyl 6,7-dimethoxy-2-(phenoxymethyl)quinoline-3-carboxylates 5a-p followed by hydrolysis with aqueous ethanolic sodium hydroxide solution. The novel synthetic method has the advantages of good yields, easy work-up, and environmentally friendly character, which may provide a novel highly efficient process for making quinoline and related azaheterocycle libraries.

黑龙江省稻田萤蔺对吡嘧磺隆的抗性监测及防治药剂筛选

为促进黑龙江稻区萤蔺的抗药性治理,采用整株剂量反应测定黑龙江省18个萤蔺种群对吡嘧磺隆的抗药性水平,通过盆栽和田间试验测试了9种替代药剂对萤蔺的防治效果。结果表明,18个种群中有4个种群(Sj6、Sj7、Sj8和Sj11)对吡嘧磺隆产生了抗性,抗性指数分别为7.48,13.60,11.42和10.41,其余13个种群为敏感种群,抗性指数为2.03~3.16;盆栽和田间药剂筛选结果发现6种药剂株防效和鲜重防效好于对照药剂10%吡嘧磺隆,其中33%嗪吡嘧磺隆、25%双环磺草酮和460 g·L^(-1)2甲·灭草松对萤蔺的盆栽和田间药后30 d株防效和鲜重防效达到90%以上。说明,黑龙江省稻区部分萤蔺种群对吡嘧磺隆产生了中等水平以下抗性,推荐在水稻生产中选用33%嗪吡嘧磺隆水分散粒剂、25%双环磺草酮悬浮剂和460 g·L^(-1)2甲·灭草松可溶液剂等药剂防除稻田萤蔺。

吡嘧磺隆二氯喹啉酸对土壤呼吸强度和酶活性的影响

采用室内模拟试验方法,研究了除草剂吡嘧磺隆、二氯喹啉酸对土壤呼吸强度和酶活性的影响。研究结果表明,吡嘧磺隆和二氯喹啉酸使用后均能刺激土壤呼吸作用,抑制土壤过氧化氢酶活性,抑制中性磷酸酶活性随后又产生一定刺激作用;吡嘧磺隆、二氯喹啉酸抑制土壤转化酶活性,在培养前期轻微刺激土壤脲酶活性而后又表现为抑制作用。

吡嘧磺隆在水稻、土壤和田水中的消解和残留

建立了水稻(糙米、稻壳和植株)、土壤和田水中吡嘧磺隆的残留分析方法.待测样品通过二氯甲烷或二氯甲烷/丙酮(1∶1,V/V)提取,C18固相萃取小柱净化后,采用高效液相色谱串联质谱(HPLC-MS/MS)测定吡嘧磺隆的含量,并研究了2010—2011年北京、安徽和海南等3地水稻、土壤和田水中吡嘧磺隆的消解动态和残留行为.实验结果表明,对水稻、土壤和田水的添加回收率均在73%—103%之间,相对标准偏差(RSD)均小于10%,在糙米、稻壳、植株、土壤、田水中的吡嘧磺隆最低检测浓度(LOQ)为0.005 mg.kg-1,符合残留试验要求.消解和残留试验结果表明,吡嘧磺隆在田水和土壤中的消解符合一级动力学,半衰期分别为5.29—6.42 d和4.99—6.42 d.秧苗期施药,收获时水稻和土壤中均未检出吡嘧磺隆的残留.