C(2)位螺环氧化吲哚化合物合成研究进展
朱宝磊，韦秋香，黄静玲，陈聚超，张振伟，陈清，林宁*
(广西中医药大学 药学院 广西壮瑶药工程技术研究中心，广西 南宁 530001）
摘要：C(2)位螺环氧化吲哚化合物存在于许多天然生物碱和生物活性物质中,具有多种生物活性，由于结构新颖、独特且合成难度较大，因此对该类化合物的合成引起了有机化学家和药物化学家的关注。在对近几年来氧化吲哚C(2)位螺环化合物合成方法调研的基础上，分别以过渡金属催化、高价碘试剂介导催化、有机催化、酸碱介导催化重排、光催化和其他催化等不同合成方法进行分类介绍该类化合物的研究进展，以期为该类化合物的后续研究提供参考。
关键词：C(2)位螺环化合物；氧化吲哚；催化；合成；研究进展
中图分类号：R914 文献标识码：A 文章编号：0258-3283（2020）
Progress for Synthesis of C(2) Spirooxindoles ZHU Bao-lei, WEI Qiu-xiang, HUANG Jing-ling, CHEN Ju-chao, ZHANG Zhen-wei, CHEN Qing, LIN Ning* (Guangxi Zhuang Yao Medicine Center of Engineering and Technology, School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530001, China), Huaxue Shiji, 2020, 42(9)
Abstract: The C(2) spirooxindoles exists in many natural alkaloids and biologically active substances, which has a variety of biological activities. Due to the novel structure, uniqueness and difficulty to synthesized, the synthesis of this class of compounds has captured attention of organic chemists and medicinal chemists. Based on the investigation of the synthesis methods of the C(2) spirooxindoles in recent years, this article reviews the progress of these compounds by transition metal catalysis, hypervalent iodine catalysis, organic catalysis, rearrangement by acid-base catalysis, photocatalysis and other catalysis, which provide valuable information for the follow-up research of these compounds.
Key words: C(2) spiro compounds; oxindoles; catalysis; synthesis; research progress
引用本文：朱宝磊，韦秋香，黄静玲，等. C(2)位螺环氧化吲哚化合物合成研究进展[J]. 化学试剂, 2020, 42(9):1019-1026.
不同锚定分子配位自组装有机太阳能电池
武彧*1，刘家成2
(1. 黔南民族师范学院 化学化工学院，贵州 都匀 558000；2. 西北师范大学 化学化工学院，甘肃 兰州 730070）
摘要：设计了含有三嗪基团的上层锌卟啉ZnPw与含有咪唑基团的锚定卟啉ZnPAim，形成轴向配位自组装体。将这种双层自组装体固定在TiO2电极表面，构建超分子染料敏化太阳能电池。对自组装ZnPw-ZnPAim电池性能测试，测试结果表明，采用锚定卟啉的自组装体具有较高的光伏性能，其中Jsc = 5.14 mA/cm2，η = 1.85%。与有机小分子锚定基团相比，双层卟啉自组装体光伏性能高出3.7倍。此外，对锚定卟啉自组装体电池的紫外-可见吸收光谱，双层自组装结构进行了表征测试。
关键词：锚定卟啉；双层；配位自组装；染料敏化太阳能电池
中图分类号：O641.4 文献标识码：A 文章编号：0258-3283（2020）
Different Anchoring Molecules Self-assembled for Dye-Sensitized Solar Cells WU Yu*1, LIU Jia-cheng2 (1. School of Chemistry and Chemical Engineering, Qiannan Normal University for Nationalities, Duyun 558000, China; 2. College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China), Huaxue Shiji, 2020, 42(9)
Abstract A novel zinc porphyrin ZnPw bearing a triazine unit has been designed to construct axial-coordinated assemblies (denoted as ZnPw-ZnPAim) with anchored porphyrin ZnPAim trough zinc-to-ligand axial coordination approach. Then these assemblies were grafted onto TiO2 electrode surface to build dye sensitized solar cells. The performance of these cells also was examined. Photoelectrochemical measurements illustrated that all the assembly based cells had certain capabilities to export photocurrent. Especially, the ZnPw-ZnPAim assembly with a anchored porphyrin based solar cell had the highest conversion efficiency of 1.85% with a JSC of 5.14 mA/cm2 among these assembly based solar cells. Compared with the anchoring group of organic small molecule, the photovoltaic performance of the self-assembled double-layer porphyrin was 3.7 times higher. In addition, the UV-Vis absorption spectrum and the double-layer self-assembly structure of the anchored porphyrin self-assembly battery were characterized.
Key words: anchored porphyrin; double-layer; coordination self-assembled; dye sensitized solar cells
引用本文：武彧，刘家成. 不同锚定分子配位自组装有机太阳能电池[J]. 化学试剂，2020，42(9)：1027-1032.
芦荟苷联合顺铂对A549细胞增殖和凋亡的影响
陈红玲，荣家闵，李鹏程，葛雅琨，张元新*
(吉林化工学院 生物与食品工程学院，吉林 吉林 132022)
摘要：探讨抗肿瘤天然药物芦荟苷（Aloin）与一线化疗药物顺铂（cisplatin，CDDP）联合对体外培养的肺癌A549细胞增殖和凋亡的影响。采用 MTT 法检测用不同浓度的顺铂、芦荟苷单独或联合作用于 A549 细胞后对其相关细胞活力的影响。用流式细胞术分析Aloin-CDPP联合对A549细胞周期、细胞凋亡以及线粒体膜电位的变化。采用western blot法检测caspase 9、caspase 3蛋白量表达的变化。MTT 结果显示芦荟苷（200 µmol/L）和顺铂（16 μg/mL）联合具有协同作用，可以抑制A549细胞增殖并可上调caspase 9、caspase 3 蛋白的表达。芦荟苷与顺铂联合作用于A549细胞后，芦荟苷能有效降低顺铂的使用浓度，并提升其诱导细胞凋亡的能力。
关键词：芦荟苷；顺铂；肺癌；协同作用；细胞凋亡
中图分类号：R734.2 文献标识码： A 文章编号：0258-3283（2020）
Effect of Aloin Combined with Cisplatin on Proliferation and Apoptosis of Lung Cancer A549 Cells CHEN Hong-ling, RONG Jia-min, LI Peng-cheng, GE Ya-kun, ZHANG Yuan-xin* (College of Food & Engineering, Jilin Institute of Chemical Technology, Jilin 132022, China), Huaxue Shiji, 2020, 42(9)
Abstract: To investigate the effect of aloin and cisplatin (CDDP) on proliferation and apoptosis of lung cancer A549 cells were cultured in vitro. The effects of different concentrations of cisplatin and aloin on the activity of A549 cells were determined by MTT method. The changes of cell cycle, apoptosis and mitochondrial membrane potential were detected by flow cytometry. The expression of cleave-caspase 9 and cleave-caspase 3 was detected by Western blot. MTT results showed that both aloin and cisplatin inhibited the proliferation of A549 cells, but aloin and cisplatin inhibited the proliferation of A549 cells significantly and had synergism, and up-regulated the expression of cleave-caspase 9 and cleave-caspase 3. Aloin can effectively reduce the concentration of cisplatin and enhance the effect of apoptosis in A549 cells.
Key words: aloin; cisplatin; lung cancer; synergistic effect; cell apoptosis
引用本文：陈红玲，荣家闵，李鹏程，等. 芦荟苷联合顺铂对A549细胞增殖和凋亡的影响[J]. 化学试剂，2020，42(9): 1033-1038.
P掺杂氮化碳催化剂可见光降解亚甲基蓝废水
艾兵*，孙天琦，刘凡，韩永磊，李德刚
(山东理工大学 化学化工学院，山东 淄博 255049)
摘要：以磷酸氢二铵和三聚氰胺为原料，采用焙烧法合成P/g-C3N4复合光催化剂。使用红外光谱（FT-IR）、荧光光谱（PL）、X射线衍射（XRD）和扫描电子显微镜（SEM）等测试手段对催化剂的结构和光学特性进行表征。结果表明：合成的P/g-C3N4复合光催化剂具有类石墨相结构，对可见光的吸收比纯g-C3N4有所增加，其荧光发射强度有所降低。可见光照射下降解亚甲基蓝废水结果显示：照射180 min，7% P/g-C3N4光催化剂对亚甲基蓝的降解率为15.3%，其反应速率常数为纯g-C3N4的1.7倍。P/g-C3N4复合光催化剂具有比纯g-C3N4更好的可见光催化降解性能。
关键词：氮化碳；磷酸氢二铵；可见光催化；荧光光谱；降解；掺杂
中图分类号：O641 文献标识码：A 文章编号：0258-3283（2020）
Visible Light Degradation of Methylene Blue Wastewater by P-doped Carbon Nitride Catalyst AI Bing*, SUN Tian-qi, LIU Fan, HAN Yong-lei, LI De-gang (School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, China), Huaxue Shiji, 2020, 42(9)
Abstract: The P/g-C3N4 composite photocatalyst was prepared from diammonium hydrogen phosphate and melamine by calcination. The structure and optical properties of the catalyst were characterized by Fourier transform infrared spectroscopy (FT-IR), photoluminescence (PL), X-ray diffraction (XRD) and scanning electron microscope (SEM). The results showed that the P/ g-C3N4 composite photocatalyst had a graphite-like phase structure, and its absorption of visible light was increased compared with that of pure g-C3N4, and its fluorescence emission intensity was decreased. The degradation of methylene blue wastewater under visible light showed that the degradation rate of methylene blue by 7% P/g-C3N4 photocatalyst was 15.3% for 180 min, and its rate constant was 1.7 times that of pure g-C3N4. The P/g-C3N4 composite photocatalyst has better visible light catalytic degradation performance than pure g-C3N4.
Key words: carbon nitride; diammonium hydrogen phosphate; visible-light photocatalysis; photoluminescence; degradation; doping
引用本文：艾兵，孙天琦，刘凡，等. P掺杂氮化碳催化剂可见光降解亚甲基蓝废水[J].化学试剂，2020，42(9):1039-1044.
铈掺杂氧化锌纳米光催化剂的制备及应用性能
王寅峰，袁善蓉，许启洋，韩慧慧，王瑶，宫培军*
（浙江师范大学 化学与生命科学学院，浙江 金华 321004）
摘要：以二水合乙酸锌、六水合硝酸铈和氨水为原料，采用沉淀法制备了一系列铈(Ce)掺杂纳米氧化锌光催化剂（x-CZO），采用X射线衍射（XRD）、X射线光电子能谱（XPS）、扫描电子显微镜（SEM）和紫外-可见漫反射谱（UV-Vis DRS）对催化剂进行表征，研究了其在可见光下催化降解罗丹明B（RhB）的性能。结果表明：Ce4+离子成功掺入六方纤锌矿结构ZnO的晶格中。随着Ce掺杂浓度的增大，x-CZO对可见光的吸收能力增强，其中1%-CZO的可见光催化性能最佳。借助静电吸附作用将1%-CZO与Fe3O4/聚乙烯亚胺纳米磁粒复合，磁性载体赋予光催化剂以快速响应外磁场和方便回收的性能，借助磁铁可以在6 min内回收92%。同时，磁性载体的存在对1%-CZO的光催化活性几乎无影响，磁性光催化剂在太阳光照射40 min时对RhB的降解率达到92%。
关键词：氧化锌；铈掺杂；光催化；磁分离；太阳光
中图分类号：TQ132.41 文献标识码：A 文章编号：0258-3283（2020）
Preparation and Application Performance of Ce-Doped Zinc Oxide Nanophotocatalysts WANG Yin-feng, YUAN Shan-rong, XU Qi-yang, HAN Hui-hui, WANG Yao, GONG Pei-jun* (College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, China), Huaxue Shiji, 2020, 42(9)
Abstract: A series of Ce-doped ZnO nanophotocatalysts (x-CZO) were prepared by using zinc acetate dihydrate, cerium nitrate hexahydrate and ammonia solution as raw materials through a precipitation method. The obtained photocatalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS), and their photocatalytic activity was evaluated by degradation of rhodamine B (RhB) under visible light irradiation. The results showed that Ce4+ ions were incorporated into the hexagonal wurtzite crystal lattice of ZnO. With the increasing dopant content, x-CZO exhibited enhanced absorption capability in the visible light region. 1%-CZO showed the best photocatalytic performance among these photocatalysts. Then, 1%-CZO was bound with Fe3O4/polyethyleneimine magnetic nanoparticles via electrostatic attraction to form a magnetically recyclable photocatalyst. The magnetic nanocarrier gave the photocatalyst an ability to sensitively respond to external magneitc fields and facilely to be recovered. 92% magnetic photocatalyst can be recovered by using a magnet within 6 min. Moreover, the magnetic nanocarrier has negligible effect on the photocatalytic activity of 1%-CZO. 92% RhB was photodegraded by the magnetic photocatalyst under 40 min of sunlight irradiation.
Key words: zinc oxide; Ce doping; photocatalysis; magnetic separation; sunlight
引用本文：王寅峰，袁善蓉，许启洋，等. 铈掺杂氧化锌纳米光催化剂的制备及应用性能[J]. 化学试剂，2020, 42(9):1045-1051.
3-羧基香豆素衍生物的合成和抗肿瘤活性
甘娜娜，谭娅玲，张静，李山诺，郑绚，季红*
（广州医科大学 药学院，广东 广州 511436）
摘要：以取代水杨醛和丙二酸二乙酯为原料，经缩合、取代和水解等反应，设计合成了10个新的3-羧基香豆素衍生物，采用1HNMR、13CNMR和 HR-MS对合成的化合物结构进行了表征，并利用MTS法考察了其对人肝癌细胞HepG2、结肠癌细胞HCT116及正常肝细胞L-02的抗增殖活性。结果表明，7-环戊氧基-3-羧基香豆素、7-环己氧基-3-羧基香豆素和7-苄氧基-3-羧基香豆素对HepG2细胞的抗增殖活性最强（IC50分别为5.02、2.94、3.65 μmol/L），而7-异丁氧基-3-羧基香豆素和7-苯乙氧基-3-羧基香豆素对HCT116细胞的活性最强，其IC50分别为5.14、9.63 μmol/L。对HepG2细胞活性最好的化合物7-环己氧基-3-羧基香豆素与顺铂（cis-DDP）联用的结果显示，该化合物能显著增强顺铂对HepG2细胞的抗增殖作用。这些研究结果可为香豆素类抗肿瘤先导化合物的研究开发提供科学依据。
关键词：3-羧基香豆素衍生物；设计；合成；抗肿瘤活性；联合用药
中图分类号：O626 文献标识码：A 文章编号：0258-3283（2020）
Synthesis and Antitumor Activity of Coumarin-3-carboxylic Derivatives GAN Na-na, TAN Ya-ling, ZHANG Jing, LI Shan-nuo, ZHENG Xuan, JI Hong* (College of Pharmacy, Guangzhou Medical University, Guangzhou 511436, China), Huaxue Shiji, 2020, 42(9)
Abstract: Ten new coumarin-3-carboxylic derivatives were designed and synthesized from substituted salicylaldehydes and diethyl malonate via condensation, substitution and hydrolyzation reactions. Their structures were characterized by 1H NMR, 13C NMR and HR-MS. The antiproliferative activity of these compounds against human liver cancer cell line HepG2, colon cancer cell line HCT116 and human normal liver cell line L-02 was evaluated by MTS method in vitro. The results showed that 7-cyclopentoxy-3-carboxyl coumarin, 7-cyclohexoxy-3-carboxyl coumarin and 7-benzyloxy-3-carboxyl coumarin had the best antiproliferative activity against HepG2 cell, their IC50 values were 5.02, 2.94 and 3.65 μmol/L, respectively. Additionally, 7-isobutyloxy-3-carboxylcoumarin and 7-phenethoxy-3-carboxylcoumarin also had potent activity against HCT116 cell with the corresponding IC50 values of 5.14 and 9.63 μmol/L. The results of the combination of the most potent 7-cyclohexoxy-3-carboxyl coumarin and cis-DDP showed that this compound significantly enhanced the antiproliferation effect of cis-DDP against HepG2 cell. The results may provide a scientific evidence for the further research and development of antitumor coumarin lead compounds.
Key words: coumarin-3-carboxylic derivatives; design; synthesis; antitumor activity; drug combination
引用本文：甘娜娜，谭娅玲，张静，等. 3-羧基香豆素衍生物的合成和抗肿瘤活性[J].化学试剂，2020，42(9):1052-1057.
铜纳米簇的合成方法、性质及其应用进展
乌日罕a，爱军*a, b
(内蒙古师范大学 a. 化学与环境科学学院，b. 内蒙古自治区绿色催化重点实验室，内蒙古 呼和浩特 010022)
摘要：铜纳米团簇是配体保护的几个或几百个金属铜原子形成的纳米粒子。铜纳米簇在溶液化学合成法中表现出低成本、多功能的颜色控制发光特性。使用不同类型的功能配体和催化剂合成铜纳米簇的方法可以调节其发射波长并改善其环境稳定性。而在合成铜纳米簇的方法中模板法应用多、效率高，其中常用的几种模板法以小分子巯基化合物、树枝大分子、多肽蛋白质、寡聚核苷酸DNA等为模板。目前，有多种的铜纳米簇陆续被制备成功，并且应用于生物、医学、环境检测、传感器和催化剂等各个领域。强调了铜纳米簇的应用潜力，并将不同配体的合成方法和功能化及其性质和应用联系起来。
关键词：铜纳米簇；模板法；DNA；荧光检测；金属离子
中图分类号：O65 文献标识码：A 文章编号：0258-3283（2020）
Synthesis, Performance and Application of Copper Nanoclusters WU Ri-hana, AI Jun*a, b (a. College of Chemistry and Environmental Science, b. Inner Mongolia Key Lab Green Catalysis, Inner Mongolia Normal University, Hohhot 010022, China), Huaxue Shiji, 2020, 42(9)
Abstract: Copper nanoclusters are nanoparticles formed by a small amount of copper atoms protected by ligands. Copper nanoclusters exhibit attractive color controlled luminescence properties with low cost and multi-function in solution chemical synthesis. Using different kinds of functional ligands and catalysts to synthesize Cu nanoclusters can adjust their emission wavelength and improve their environmental stability. The template method is the most efficient in the synthesis of copper nanoclusters, among which the commonly used template methods are small mercapto compounds, dendrimers, polypeptide proteins, oligonucleotide DNA and so on. Nowadays, many kinds of copper nanoclusters have been successfully prepared, and have been applied in various fields such as biology, medicine, environmental detection, sensors and catalysts. In this review, the potential applications of copper nanoclusters are emphasized, and the synthesis and functionalization of different ligands are related to their properties and applications.
Key words: copper nanoclusters; template method; DNA; fluorescence detection; metal ion
引用本文：乌日罕，爱军. 铜纳米簇的合成方法、性质及其应用进展[J]. 化学试剂，2020, 42(9):1058-1066.
枇杷核不同极性萃取物总黄酮、总多酚含量与其抗氧化活性的相关性
王萍1, 2，王宇鹤3，李辉4，赖普辉*1, 2，高寒1
(1. 陕西国际商贸学院 医药学院，陕西 西安 712046；2. 陕西省中药绿色制造技术协同创新中心，陕西 西安 712046；3. 西藏民族大学 医学部临床医院，陕西 咸阳 712082；4. 浙江康恩贝制药股份有限公司，浙江 兰溪 321109）
摘要：研究枇杷核石油醚、氯仿、乙酸乙酯、正丁醇、水等不同极性溶剂萃取物中总黄酮、总多酚的含量及其抗氧化活性相关性。采用比色法测定5种萃取物中总黄酮和总多酚含量，通过测定DPPH 自由基清除率、ABTS+自由基清除率、OH-自由基清除率及还原能力评价不同极性萃取物抗氧化活性的差异。结果表明，枇杷核各萃取物均有抗氧化活性，且均呈量效关系，其中乙酸乙酯萃取物清除能力最强，石油醚萃取物清除能力最弱；总多酚含量与DPPH、ABTS+、还原能力呈显著性相关，可为枇杷核作为天然抗氧化剂的开发提供理论依据。
关键词：枇杷核萃取物；总黄酮；总多酚；抗氧化活性；相关性
中图分类号：R284 文献标识码：A 文章编号：0258-3283（2020）
Correlation between the Content Total Flavonoids and Total Polyphenols in Loquat Nuclear with Different Extracts and Their Antioxidant Activities WANG Ping1,2, WANG Yu-he3, LI Hui4, LAI Pu-hui*1,2, GAO Han1 (1. College of Medicine, Shaanxi Institute of International Trade&Commerce, Xi’an 712046, China; 2. Collaborative Innovation Center of Green Manufacturing Technology for Traditional Chinese Medicine in Shaanxi Province, Xi’an 712046, China; 3. Clinical Hospital, Department of Medicine, Xizang Minzu University, Xianyang 712082, China; 4. Zhejiang Conba Pharmaceutical Co., Ltd., Lanxi 321109, China), Huaxue Shiji, 2020, 42(9)
Abstract：To study the correlation of the contents of total flavonoids, total polyphenols and their antioxidant activities in petroleum ether extract, chloroform extract, ethyl acetate extract, n-butanol extract and water extract from Loquat nuclear. The contents of total flavonoids and total polyphenols in 5 extracts were determined by colorimetric method, and the antioxidant activities of extracts were evaluated and analyzed by the determination of DPPH radical scavenging ability, ABTS+ radical scavenging ability ,OH- radical scavenging ability and reducing power. All extracts from Loquat nuclear had antioxidant activity and showed a dose effect relationship. The total polyphenol content was significantly correlated with DPPH, ABTS+ and reducing ability, which could provide a theoretical basis for the development of Loquat kernel as a natural antioxidant.
Key words: Loquat nuclear; total flavonoids; total polyphenols; antioxidant activities; correlation
引用本文：王萍，王宇鹤，李辉，等. 枇杷核不同极性萃取物总黄酮、总多酚含量与其抗氧化活性的相关性[J]. 化学试剂，2020，42(9):1067-1072.
四川省Y县稻谷和农田土壤中重金属
含量测定及致癌风险评价
任婷1，钟文思2，赵丽娇*1，曾毅1
（1. 北京工业大学 生命科学与生物工程学院 环境与病毒肿瘤学北京市重点实验室，北京 100124；
2. 佐治亚理工学院 化学与分子生物工程系，亚特兰大 GA 30332，美国）
摘要：建立并优化了高分辨连续光源原子吸收光谱法(HR-CS AAS)测定稻田土壤及水稻可食用籽粒中铬(Cr)、镉(Cd)、铅(Pb)和砷(As)含量的测定方法。4种重金属的方法检出限(LOD)分别为0.025、0.011、0.012和0.006 µg/L；土壤标准品回收率98.3%～99.3%，大米粉标准物质回收率为98.4%～99.6%。应用该方法对四川省Y县稻田土壤和稻粒样品中4种重金属元素进行了定量分析，结果表明，土壤样品中重金属平均含量均小于国标农用地土壤风险筛选值，有3.7%土壤样品中Cd超标；稻粒样品中重金属含量平均值都在国标食品中污染物的限量范围内，有15%的稻粒样品中Cr含量超标。采用美国环境保护署(USEPA)建议的致癌风险模型分别对土壤和稻粒中重金属暴露进行了致癌风险评价。结果表明，稻田土壤中重金属经各种途径暴露对人类的致癌风险均在可接受范围内。稻粒中重金属经口摄入对人类的总致癌风险指数为1.48´10-3，潜在致癌风险超出可接受范围。稻谷可食用部分的经口摄入是当地居民暴露于重金属的主要途径；可能是导致当地胃癌高发病率的重要影响因素之一。
关键词：重金属；农田土壤；稻谷；致癌风险评价；原子吸收光谱法
中图分类号：X503 文献标识码：A 文章编号：0258-3283（2020）
Determination and Carcinogenic Risk Assessment of Heavy Metals in Rice Grain and Paddy Soil in Y County, Sichuan Province REN Ting1, ZHONG Wen-si2, ZHAO Li-jiao*1, ZENG Yi1 (1. Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China; 2. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta GA 30332, USA), Huaxue Shiji, 2020, 42(9)
Abstract：A method for the determination of chromium (Cr), cadmium (Cd), lead (Pb) and arsenic (As) in paddy soil and edible rice grains by high resolution continuum source atomic absorption spectrometry (HR-CS AAS) was established and optimized. The LOD of four heavy metals were 0.025, 0.011, 0.012 and 0.006 μg/L, respectively. The recovery of soil standard was 98.3%-99.3%, and that of rice flour standard was 98.4%-99.6%. The method was applied to the quantitative analysis of four heavy metals in the paddy soil and rice grain samples of Y county, Sichuan province. The results showed that the average contents of heavy metals in the soil samples were lower than the national standard agricultural soil risk screening values, while 3.7% of the contents of Cd in soil samples exceeded the standard value. The average contents of heavy metals in the rice grain samples were within the national food pollutants standard limitation, and 15% of contents of Cr in the rice grain samples exceeded the limitation. The carcinogenic risk model proposed by the United States Environmental Protection Agency (USEPA) was used to evaluate the carcinogenic risk of heavy metals in soil and rice grain. The results showed that the carcinogenic risk of heavy metals in paddy soil which were exposed by various ways to human beings was acceptable. The total carcinogenic risk index of heavy metals in rice grains was 1.48´10-3, and the potential carcinogenic risk was beyond the acceptable range. Oral intake of edible parts of rice was the main exposure way of heavy metals for local residents, which may be one of the important factors that cause high incidence rate of gastric cancer in the local area.
Key words: heavy metals; paddy soil; rice grain; carcinogenic risk assessment; atomic absorption spectrometry
引用本文：任婷，钟文思，赵丽娇，等. 四川省Y县稻谷和农田土壤中重金属含量测定及致癌风险评价[J]. 化学试剂, 2020, 42(9):1073-1077.
液相色谱串联质谱检测鹿茸及其制品中孕酮等5种性激素
王佳慧，杨帆，高明，付瑶，胡婷婷，王准，张勋*
（长春海关技术中心，吉林 长春 130062）
摘要：建立了固相萃取-液相色谱-串联质谱法测定鹿茸及其制品中孕酮、睾酮、雌酮、皮质甾酮、雌二醇5种性激素的分析方法。比较了不同提取液对目标物质的提取效果，所测样品经乙腈提取，提取液经HLB固相萃取柱净化，10%甲醇水淋洗杂质，7 mL乙腈洗脱后收集洗脱液氮吹至近干，用1 mL V（甲醇）∶V（0.1%甲酸溶液） = 4∶6复溶，在LC-MS/MS多反应监测(MRM)模式下进行了定性和定量分析。在上述检测方法条件下，所测的5种性激素的最低检出限均为0.001 mg/kg，平均回收率在87.3%～94.4%之间，RSD在3.87%～7.68%之间，线性范围为0.001～0.2 mg/kg呈良好的线性关系，相关系数r > 0.999。该方法操作简便，检测结果准确，可以满足鹿茸及其制品中雌性激素的检测要求。
关键词：固相萃取；鹿茸；性激素；液相色谱-串联质谱法
中图分类号：O657.63 文献标识码：A 文章编号：0258-3283（2020）
Determination of Five Estrogens in Pilose Antler and Its Products by Liquid Chromatography-tandem Mass Spectrometry WANG Jia-hui, YANG Fan, GAO Ming, FU Yao, HU Ting-ting, WANG Zhun, ZHANG Xun* (Changchun Customs Technology Center, Jilin 130062, China), Huaxue Shiji, 2020, 42(9)
Abstract: A method for the determination of progesterone, testosterone, estrone, corticosterone and estradiol in human pilose antler and its products by solid phase extraction-liquid chromatography-tandem mass spectrometry was established. Comparing the effect of different reagent extraction, the samples were extracted by acetonitrile and purified by HLB solid phase extraction column. Wash away impurities by the 10% methanol water and get the target compounds by 7 mL acetonitrile. Use 1 mL V (methanol)∶V (0.1% formic acid) = 4∶6 dissolved again after the eluent was nearly dry by the nitrogen at the last time .Qualitative and quantitative analysis methods were carried out under the mode of LC-MS/MS multi-reaction monitoring (MRM). Under the above conditions, the minimum detection limit of the five estrogens was 0.001 mg/kg, the average recovery was 87.3%～94.4%, RSD was 3.87%～7.68% and the linear range was 0.001～0.2 mg/kg, r > 0.999. The method is simple to operate and the accurate results could be applied for determination 5 kinds of estrogens in pilose antler and its products.
Key words: solid phase extraction; pilose antler; estrogen; LC-MS/MS
引用本文：王佳慧，杨帆，高明，等. 液相色谱串联质谱检测鹿茸及其制品中孕酮等5种性激素[J]. 化学试剂，2020, 42（9）：1078-1082.
吡啶并氟硼荧光染料的构建及在苦味酸识别中的应用研究
吕荫妮，李宏达*
（中国刑事警察学院 法化学系，辽宁 沈阳 110035）
摘要：以3-吡啶甲醛和2,4-二甲基吡咯为原料，合成了吡啶并氟硼荧光染料探针mPBP。通过1HNMR和ESI-MS进行了结构表征。在含80%DMSO水溶液中，荧光探针对苦味酸（PA）具有良好的选择性和灵敏度。探针mPBP不到30 s就能够与PA完全反应，可以快速、高效地识别PA，能够满足现场快速检测识别的要求。荧光探针mPBP与不同浓度的PA呈现良好的线性关系，最低检测浓度为12.58 nmol/L。探针mPBP成功的应用于河水样品中加标PA含量的检测，获得了很好的回收率（96.0%～105.0%）。另外，明显的溶液颜色变化（亮绿色到无色），可以作为快速可视化识别复杂环境样品中PA的化学传感器。
关键词：染料；苦味酸检测；荧光分析；化学传感器；可视化识别
中图分类号：D918.93 文献标识码：A 文章编号：0258-3283（2020）
Construction of Pyridine-boron Dipyrromethene Dye and Application Research in Picrate Recognition LV Yin-ni, LI Hong-da* (Department of Forensic Chemistry, Criminal Investigation Police University of China, Shenyang 110035, China), Huaxue Shiji, 2020, 42(9)
Abstract: 3-Pyridine formaldehyde and 2,4-dimethyl pyrrole as raw material, fluorescent probe mPBP was synthesized based on pyridine-boron dipyrromethene dye. The structure of probe was characterized by 1H NMR and ESI-MS. Fluorescent probe has good selectivity and sensitivity of PA in water containing 80% DMSO aqueous solution. Probe mPBP can react with PA completely less than 30 s, can quickly and effectively identify PA, can meet the requirements of on-site rapid detection of recognition. Fluorescent probe mPBP with good linear relation with the different concentrations of PA, the limit of detection was 12.58 nmol/L. Probe mPBP successful applied in river water samples to add the PA content detection, obtained the very good recovery rate (96.0%～105.0%). In addition, the obvious solution change color (light green to colorless), can be used as a quick visual identification of PA-chemosensor in a complex environment sample.
Key words: dye; picrate detection; fluorescent analysis; chemosensor; visual recognition
引用本文：吕荫妮，李宏达. 吡啶并氟硼荧光染料的构建及在苦味酸识别中的应用研究[J]. 化学试剂, 2020, 42(9): 1083-1087.
二氧化钛光催化对小麦呕吐毒素降解效果的研究
单晓雪，杨娟，廖子龙，张宇冲，姜友军，陈晋莹*
(中储粮成都储藏研究院，四川 成都 610000)
摘要：以未固化加工的纳米级试剂二氧化钛（TiO2）为研究对象，对小麦中呕吐毒素（DON）的降解情况进行研究。通过在小麦粉和籽粒中添加TiO2，进行一系列的正交试验，观察小麦DON的降解效果，最后再验证添加TiO2对小麦的出粉率、色泽、气味、脂肪酸值、粗蛋白等相关品质指标影响情况。研究结果表明光照2 h，小麦粉和籽粒实验组降解率提升最快，相对降解率最高，紫外照射6 h，紫外光光催化TiO2与紫外光协同作用使DON降解率可分别达到40.0%和32.8%，说明粉状未加工的纳米级TiO2对小麦DON的有较明显的降解效果。
关键词：二氧化钛；光催化降解；紫外光照；小麦呕吐毒素；品质指标；
中图分类号：S512.1, ST21 文献标识码：A 文章编号：0258-3283（2020）--
Degradation of wheat vomiting toxin by titanium dioxide photocatalysis SHAN Xiao-xue, YANG Juan, LIAO Zi-yong, ZHANG Yu-chong, JIANG You-jun, CHEN Jin-ying* (Sinograin Chengdu Storage Research Institute co. Ltd., ChengDu, 610000), Huaxue Shiji, 2020, 42(9 )
Abstract：In this paper, the degradation of DON in wheat was studied with uncured nano-scale reagent TiO2 as the research object.By adding TiO2 to wheat flour and grains, a series of orthogonal experiments were conducted to observe the degradation effect of wheat DON. Finally, the effects of adding TiO2 on wheat yield, color, odor, fatty acid value, crude protein and other related quality indicators were verified.The results showed that the degradation rate of wheat flour and grains in the experimental group was the fastest and the relative degradation rate was the highest after 2 h of light exposure. After 6 h of uv irradiation, the degradation rate of DON was 40.0 % and 32.8 % respectively under the synergistic effect of uv photocatalysis TiO2 and uv light, indicating that the degradation effect of powdered unprocessed nano-scale TiO2 on wheat DON was obvious.
Key words: titanium dichloride; UV-irradiation; photocatalytic degradation; wheat vomiting toxin; quality indicators
引用本文：单晓雪, 杨娟, 廖子龙, 等. 二氧化钛光催化对小麦呕吐毒素降解效果的研究[J]. 化学试剂, 2020, 42( ): 1088-1092.
响应面法优化侧柏叶总黄酮提取工艺
黄小梅，胡孝勇*，左华江
（广西科技大学 生物与化学工程学院，广西 柳州 545006）
摘要：利用超声波辅助提取侧柏叶总黄酮，用分光光度法分析其含量。研究了乙醇浓度、超声提取时间、液料比对侧柏叶总黄酮提取的影响。在单因素实验的基础上，以侧柏叶总黄酮提取率为响应值，以乙醇浓度、超声提取时间、液料比为自变量，通过三因素三水平Box-Bohnken 响应面分析法对筛选出的提取工艺进行优化。结果表明，响应面法优化得到的最佳提取工艺为：在乙醇浓度73%、提取时间42min、液料比为80:1，此实验条件下重复3次做验证实验得到的侧柏叶总黄酮平均提取率为2.45%，与Box-Bohnken 响应面分析法模拟预测值2.47%相差较小，所建模型与采用的优化方法可靠。
关键词：侧柏叶；总黄酮；提取工艺；响应面法；优化
中图分类号：R284.2 文献标识码：A 文章编号：0258-3283（2020）
Optimization of Extraction Process of Total Flavonoids from Platycladus Orientalis Leaves by Response Surface Methodology HUANG Xiao-mei, HU Xiao-yong*, ZUO Hua-jiang (College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou 545006, China), Huaxue Shiji, 2020, 42(9)
Abstract: The total flavonoids of Platycladus orientalis leaves were extracted with the aid of ultrasound, and their contents were analyzed by spectrophotometry. The effects of ethanol concentration, ultrasonic extraction time and liquid-to-material ratio on the extraction of total flavonoids in Platycladus orientalis leaves were investigated. Based on the single factor experiment, the total flavonoids extraction rate of Platycladus orientalis leaves was taken as the response value, and the ethanol concentration, ultrasonic extraction time, and liquid-to-material ratio were used as independent variables. The optimized extraction process was investigated. The optimal extraction process obtained by response surface method optimization was ethanol concentration of 73%, extraction time of 42 min, and a liquid-to-material ratio of 80:1. On this condition repeating the verification experiment three times under obtainthe the total flavonoids extraction rate of Platycladus orientalis leaves the average extraction rate is 2.45%, which is near from the Box-Bohnken response surface analysis simulation prediction value of 2.47%. The model established is reliable with the optimization method used.
Key words: Platycladus orientalis leaves; total flavonoids; extraction process; response surface method; optimization
引用本文：黄小梅，胡孝勇，左华江. 响应面法优化侧柏叶总黄酮提取工艺[J]. 化学试剂，2020，42(9):1093-1097.
环保用四氯乙烯的提纯工艺研究
赵文伯1，张雪容2，李晨星1，吴林科1，陈雅琪1，刘晨阳1，何晖*3
（1. 郑州师范学院 化学化工学院，河南 郑州 450044；2. 广东省环境监测中心，广东 广州 510308；
3. 全国化学试剂信息总站，北京 100050）
摘要：水中油含量测定新国标（HJ 637 - 2018）采用四氯乙烯为萃取剂，但市售普通四氯乙烯不能满足新国标使用要求。为得到满足新国标使用的合格四氯乙烯产品，对四氯乙烯试剂的提纯工艺条件进行了探究，找到了先脱水、再过滤、最后精馏的提纯工艺流程，具体工艺条件为：脱水剂优选变色硅胶，脱水时间以加入变色硅胶直至沉入容器底部为参照，约为5 min；过滤介质优选经600 ℃以上灼烧的硅酸铝纤维棉；精馏条件优选全回流20 min，回流比0.25，填料层高为1300 mm。经上述纯化工艺处理后，四氯乙烯在3030、2960、2930 cm-1处吸光度分别小于0.0000、0.0321和0.3147，满足新国标中四氯乙烯的吸光度分别小于0、0.07和0.34的要求。
关键词：四氯乙烯；提纯；环保；红外分光光度法；脱水；过滤；精馏
中图分类号：TQ421.3 文献标识码：A 文章编号：0258-3283（2020）
Study on Purification Process of Environmental Tetrachloroethylene ZHAO Wen-bo1, ZHANG Xue-rong2, LI Chen-xing1, WU Lin-ke1, CHEN Ya-qi1, LIU Chen-yang1, HE Hui*3 (1. School of Chemistry and Chemical Engineering, Zhengzhou Normal University, Zhengzhou 450044, China; 2. Guangdong Environmental Monitoring Center, Guangzhou 510308, China; 3. Chemical Reagents Information Center of China, Beijing 100050, China), Huaxue Shiji, 2020, 42(9)
Abstract: The new national standard for determination of oil content in water (HJ 637—2018) uses tetrachloroethylene as the extractant, but commercially available ordinary tetrachloroethylene cannot meet the requirements of the new national standard. In order to obtain qualified tetrachloroethylene products that meet the new national standard, this article explored the purification process conditions of the tetrachloroethylene reagent, and found the purification process flow of dehydration, filtration, and final distillation. The specific process conditions are: The dehydrating agent is preferably color-changing silica gel, and the dehydrating time is about 5 min with reference to adding the color-changing silica gel until it sinks into the bottom of the container; the filter medium is preferably aluminum silicate fiber cotton burned above 600 °C. The rectification conditions are preferably total reflux for 20 min, the reflux ratio is 0.25, and the filler layer height is 1300 mm. After the above purification process, the absorbance of tetrachloroethylene at 3030, 2960 and 2930 cm-1 is less than 0.0000, 0.0321 and 0.3147. It meets the requirements that the absorbance of tetrachloroethylene in the new national standard is less than 0, 0.07 and 0.34, respectively.
Key words: tetrachloroethylene; purification; environment; infrared spectrophotometry; dehydration; filter; rectification
引用本文：赵文伯, 张雪容, 李晨星, 等. 环保用四氯乙烯的提纯工艺研究[J]. 化学试剂, 2020, 42(9):1098-1101.
抗肿瘤药物恩曲替尼的合成工艺优化
刘彦，范为正，冯柏年*
(江南大学 药学院，江苏 无锡 214122）
摘要：改进了抗肿瘤药物恩曲替尼的合成工艺。以4-氟-2-硝基苯甲酸为起始原料，经酯化反应、亲核取代、还原、亲核加成、三氟乙酰基保护、水解后得到4-(4-甲基哌嗪-1-基)-2-[2,2,2-三氟-N-(四氢-2H-吡喃-4-基)乙酰胺基]苯甲酸。2-氟-5-溴苯腈和硼酸三甲酯发生亲核取代，再与3,5-二氟苄溴发生Suzuki偶联反应，经成环后得5-(3,5-二氟苄基)-1H-吲唑-3-胺。4-(4-甲基哌嗪-1-基)-2-[2,2,2-三氟-N-(四氢-2H-吡喃-4-基)乙酰胺基]苯甲酸与5-(3,5-二氟苄基)-1H-吲唑-3-胺发生缩合反应，再经脱三氟乙酰基得到目标化合物恩曲替尼，纯度99.12％，总产率26.0％(以4-氟-2-硝基苯甲酸计)。相比于文献路线，合成工艺缩短了酰胺的合成步骤，进行了原工艺中价格昂贵的原料—(3-氰基-4-氟苯基)硼酸的合成，节约了成本，优化了多步反应的条件及后处理方法。改进后的合成路线具有原料易得、操作简便、产率高的特点，更适合工业化生产。
关键词：恩曲替尼；酪氨酸激酶抑制剂；抗肿瘤药；合成；工艺优化
中图分类号：R914 文献标识码：A 文章编号：0258-3283（2020）
Optimization of Synthetic Process of Antitumor Drug Entrectinib LIU Yan, FAN Wei-Zheng, FEN Bai-nian*(School of Pharmacy, Jiangnan University, Wuxi 214122, China), Huaxue Shiji, 2020, 42(9)
Abstract: The synthesis process of the antitumor drug entrectinib has been improved. Using 4-fluoro-2-nitrobenzoic acid as the starting material, 4-(4-methylpiperazin-1-yl)-2-[2,2,2-trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido] benzoic acid was obtained after esterification, nucleophilic substitution, reduction, nucleophilic addition, trifluoroacetyl protection, and hydrolysis. The product obtained after nucleophilic substitution of 2-fluoro-5-bromobenzonitrile and trimethyl borate was then subjected to Suzuki coupling reaction with 3,5-difluorobenzyl bromide. The product underwent ring formation to give 5-(3,5-difluorobenzyl)-1H-indazol-3-amine. 4-(4-methylpiperazin-1-yl)-2-[2,2,2- trifluoro-N-(tetrahydro-2H-pyran-4-yl)acetamido]benzoic acid and 5-(3,5-difluorobenzyl)-1H-indazol-3-amine underwent condensation reaction to obtain the product, and then the trifluoroacetyl group was removed to obtain the target compound entrectinib, purity 99.12%, total yield 26.0% (Based on 4-fluoro-2-nitrobenzoic acid). Compared with the literature route, the synthesis process shortens the synthesis steps of the amide and synthesizes (3-cyano-4-fluorophenyl)boronic acid, an expensive raw material in the original process, saving costs, optimizing the conditions and post-treatment of the multi-step reaction method. The improved synthetic route has the characteristics of easy availability of raw materials, simple operation and high yield, and is more suitable for industrial production.
Key words: Entrectinib; tyrosine kinase inhibitors; antitumor drug; synthesis; process optimization
引用本文：刘彦, 范为正, 冯柏年. 抗肿瘤药物恩曲替尼的合成工艺优化[J]. 化学试剂, 2020, 42(9): 1102-1107.
4-二甲氨基吡啶催化合成苯妥英钠的研究
陈艳君* a,b, 史海波a,b, 刘艳a,b, 邵柯妹a, 蒋梦吉a, 袁道远a, 金丽莎a, 文志强a
（宁波职业技术学院 a.乙烯工程副产物高质化利用浙江省应用技术协同创新中心，b. 化学工程学院，浙江 宁波 315800）
摘要：苯妥英钠是抗癫痫发作的首选用药。以安息香为原料，经氧化、环缩合、成盐3步反应制得苯妥英钠。环缩合步骤首次采用4-二甲氨基吡啶为催化剂，在V（正丁醇）∶V（水）= 1∶1组成的两相体系中，完成联苯甲酰与尿素的环缩合反应，高效得到苯妥英，然后与10 %氢氧化钠乙醇溶液成盐得苯妥英钠，目标化合物的结构经IR和1HNMR确认。该合成路线具有操作简单、后处理方便、产品纯度高且收率高等优点，适合工业化生产，总收率为84.96%。
关键词：安息香；联苯甲酰；苯妥英钠；4-二甲氨基吡啶；缩合反应；合成
中图分类号：O625.5 文献标识码：A 文章编号：0258-3283（2020）
Phenytoin Sodium Catalyzed by 4-Dimethylamino Pyridine CHEN Yan-jun*a,b, SHI Hai-boa,b, LIU Yan a,b, SHAO Ke-meia, JIANG Meng-jia, YUAN Dao-yuana, JIN Li-shaa, WEN Zhi-qianga (a. Zhejiang Collaborative Innovation Center for High Value Utilization of Byproducts from Ethylene Project, b. College of Chemical Engineering, Ningbo Polytechnic, Ningbo 315800, China), Huaxue Shiji, 2020, 42(9)
Abstract: Phenytoin sodium is commonly used as antiepileptic drug. The synthesis route of the title compound was improved. Benzoyl was condensed with urea to afford phenytoin by 4-dimethylaminopyridine as catalyst in two-phase system, composed of n-butanol and water (volume ratio 1:1). Phenytoin sodium was formed by phenytoin and 10% sodium hydroxide ethanol solution. The target product and intermediates were confirmed by IR and 1HNMR. The synthetic route was easy to operate and the product was easy to purify with higher purity. The total yield was 84.96 %, which is suitable for industrial production．
Key words: benzoin; Benzoyl; sodium phenytoin; 4-dimethylaminopyridine; condensation; synthesis
引用本文：陈艳君，史海波，刘艳，等. 4-二甲氨基吡啶催化合成苯妥英钠的研究[J].化学试剂，2020，42(9): 1108-1111.
一种新型吲哚并咔唑化合物的合成与表征
段陆萌*1，李仲庆1，马则群2，陈婷1，梁现丽1，杭德余1
（1. 北京燕化集联光电技术有限公司，北京 102502；2. 北京理工大学 化学与化工学院，北京 100081）
摘要：5-（[1,1’-二联苯]-4-基）-5,11-二氢吲哚[3,2-b]咔唑为有机电致发光材料和光电催化材料重要中间体。以3-溴咔唑和4-碘联苯为原料，经过Ullmann反应、Buchwald-Hartwig偶联反应和分子内Heck偶联反应生成目标化合物。通过对催化剂、配体和溶剂等条件的优化，确定合成9-[1,1'-联苯-4-基]-3-溴-9H-咔唑的最佳工艺为：催化剂为氯化亚铜、配体为1,10-菲罗啉、溶剂为N,N-二甲基甲酰胺（DMF）；目标化合物提纯的最优条件为6倍体积四氢呋喃。合成的化合物经过高效液相色谱仪测试纯度，DSC差示扫描量热仪测试熔点，1H NMR确定结构。
关键词：有机电致发光材料； 光电催化材料； 吲哚并咔唑；咔唑；联苯
中图分类号：O626.13 文献标识码：A 文章编号：0258-3283（2020）
Synthesis and Characterization of a Novel Indolocarbazole Compound DUAN Lu-meng*1, LI Zhong-qing1, MA Ze-qun2, CHEN Ting1, LIANG Xian-li1, HANG De-yu1 (1. Beijing Yanhua Jilian Optoelectronic Technology Co., Ltd., Beijing 102502, China; 2. School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China), Huaxue Shiji, 2020, 42(9)
Abstract: 5-([1,1'-Biphenyl]-4-yl)-5,11-dihydroindolo[3,2-b]carbazole (compound 3) is an important intermediate to prepare organic electroluminescent materials or photoelectrocatalytic materials. It was synthetised by Ullmann reaction, Buchwald-Hartwig coupling reaction and intramolecular Heck coupling reaction, in which 3-bromocarbazole and 4-iodobiphenyl were used as reactants. The optimum reaction conditions were determined by optimizing the conditions such as the catalyst, ligand, solvent and so on. The optimum catalyst, ligand and solvent were cuprous chloride, 1,10-phenanthroline, DMF, respectively when 9-[1,1'-biphenyl-4-yl]-3-bromo- 9H-carbazole was synthesised; the optimal purification condition for compound 3 was tetrahydrofuran of 6 times volume. The purity and melting points of synthetic compounds were tested by HPLC and DSC, respectively, their structure was determined by 1H NMR.
Key words: organic electroluminescent materials; photocatalytic materials; indolocarbazole
引用本文：段陆萌, 李仲庆, 马则群, 等. 一种新型吲哚并咔唑化合物的合成与表征[J]. 化学试剂, 2020, 42(9): 1112-1115.
碘催化合成取代芳基硫醚衍生物
周海平*，贺新
（常州工程职业技术学院 化工与制药工程学院，江苏 常州 213164）
摘要：取代芳基硫醚衍生物存在于许多药物结构中，通常具有多种生物活性。过渡金属催化的合成方法成本高、条件苛刻，不适合大量生产，因此需要开发绿色合成方法。通过氮杂环取代吡咯及其衍生物为起始原料和碘作为催化剂，与芳基二硫醚反应制备获得产品，并对催化剂种类及用量、溶剂、缚酸剂、温度和反应时间进行研究。得到了8个结构新颖的取代含氮杂环吡咯硫醚，产率为78%～92%，结构经1H NMR、13C NMR和HR-MS确证。方法具有操作简便、反应产率高的特点，有利于取代芳基硫醚衍生物的绿色合成。
关键词：芳基硫醚；碘；C—H活化；硫化反应；合成
中图分类号：O621.3 文献标识码：A 文章编号：0258-3283（2020）
Synthesis of Substituted Aryl Sulfide Derivatives Catalyzed by Iodine ZHOU Hai-ping*, HE Xin (College of Chemical and Pharmaceutical Engineering, Changzhou Institute of Engineering Technology, Changzhou 213164, China), Huaxue Shiji, 2020,42( ), ～
Abstract: Substituted aryl thioether derivatives existing in structures of many drugs usually have various biological activities. The transition-metal-catalyzed synthesis method requires high cost and harsh conditions, which is not suitable for mass production. Therefore, it is necessary to develop green synthesis methods. Using nitrogen-heterocyclic pyrrole and its derivatives as starting materials and iodine as catalyst, the product was prepared by reaction with aryl disulfide, and the types and amount of catalyst, solvent, acid-binding agent, temperature and reaction time were studied. In this manuscript, 8 novel substituted nitrogen-heterocyclic pyrrole thioethers were obtained yielding from 78% to 92%, and the structures were confirmed by 1H NMR, 13C NMR and HR-MS. This method has the advantages of simple operation, high yield, and is beneficial to the green synthesis of substituted aryl thioether derivatives.
Key words: aryl sulfide; iodine; C—H activation; sulfurization reaction; synthesis
引用本文：周海平, 贺新. 碘催化合成取代芳基硫醚衍生物[J]. 化学试剂, 2020, 42(9):1116-1119.
兰索拉唑潜在杂质的合成
杨良1,2，张毅1,2，朱高峰2，金幸3，王建塔*1,2，汤磊*2
（1. 贵州医科大学 药学院，贵州 贵阳 550004；2. 贵州省化学合成药物研发利用工程技术研究中心，贵州 贵阳 550004；3. 上海慈瑞医药科技股份有限公司，上海 201109）
摘要：根据兰索拉唑原料药合成方法及注射剂制备工艺分析可能产生的潜在杂质，并进行合成。以邻苯二胺为起始原料分别进行源自2-羟基苯并咪唑或2-巯基苯并咪唑的4个潜在杂质的合成。目标化合物经高效液相色谱法测定纯度后采用红外光谱、核磁共振氢谱、核磁共振碳谱以及高分辨质谱进行化学结构确证。合成化合物的纯度均大于98.5%，结构确证数据与目标化合物相符。4个潜在杂质的制备方法简便、纯度高，可作为对照品用于兰索拉唑未知杂质的的分析和鉴定。
关键词：兰索拉唑；潜在杂质；对照品；合成；结构确证
中图分类号：R97 文献标识码：A 文章编号：0258-3283（2020）
Synthesis of Potential Impurities of Lansoprazole YANG Liang1,2, ZHANG Yi1,2, ZHU Gao-feng2, JIN Xing3, WANG Jian-ta*1,2, TANG Lei*2 (1. School of Pharmacy, Guizhou Medical University, Guiyang 550004; 2. Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guiyang 550004; 3. Shanghai CRMED Science Co., Ltd., Shanghai 201109, China), Huaxue Shiji, 2020, 42(9)
ABSTRACT: According to the synthesis method of Lansoprazole and the preparation process of injection, the potential impurities were analyzed and synthesized. Four potential impurities of Lansoprazole which generated from 2-hydroxybenzimidazole or 2-mercaptobenzimidazole were prepared using o-phenylenediamine as the starting material. The purity of the title compounds were determined by HPLC, and the structures were confirmed by IR, 1H NMR, 13C NMR and HR-MS. The purity of these compounds were more than 98.5%, and the structural confirmation data was consistent with the title compounds. Synthetic procedure of the four potential impurities was simple and high in purity, which can be used as reference substances for the analysis and identification of unknown impurities in Lansoprazole.
Key words: Lansoprazole; potential impurities; reference substance; synthesis; structural confirmation
引用本文：杨良，张毅，朱高峰，等. 兰索拉唑潜在杂质的合成[J]. 化学试剂，2020，42(9): 1120-1124.
趋化因子受体2抑制剂PF-04136309的合成研究
颜延宁*，周鑫鑫
(江苏食品药品职业技术学院 健康学院，江苏 淮安 223003)
摘要：对CCR2抑制剂PF-04136309的合成路线进行改进和优化。以2-溴-5-氯吡啶、间三氟甲基苯甲酸、1,4-环己二酮单乙二醇缩酮为起始原料，经过缩合、亲核加成、偶联、脱保护、还原等7步反应制备获得PF-04136309。通过优化合成路线，关键中间体4-羟基-4-[2-(2-嘧啶基)-5-吡啶基]环己酮的产率得到了较大幅度的提升，采用Suzuki-Miyaura反应代替镍催化剂的使用避免了无水无氧反应条件，使后处理纯化步骤较现有文献简化。通过优化后的反应路线，PF-04136309的总产率达到44.9%（以2-溴-5-氯吡啶计），较文献报道总产率30.2%（以2,5-二溴吡啶计）有了较大幅度的提升。该合成方法具有原料易得、操作简便、路线简短、产率较高等优点。
关键词：PF-04136309；CCR2抑制剂；合成；工艺优化；核磁表征
中图分类号：R914.5 文献标识码：A 文章编号：0258-3283（2020）--
Synthesis of CCR2 Inhibitor PF-04136309 YAN Yan-ning*, ZHOU Xin-xin ( Jiang Su Food & Pharmaceutical Science College, Huaian 223003, China), Huaxue Shiji, 2020, 42(9), ～
Abstract：To improve and optimize the synthetic route of CCR2 inhibitor (PF-04136309), PF-04136309 was synthesis by using 2-bromo-5-chloropyridine, m-trifluoromethylbenzoic acid, 1,4-cyclohexanedione monoethylene glycol ketal as starting materials, through condensation, nucleophilic addition, coupling, deprotection, and reduction in 7 steps. The yield of 4-hydroxy-4-[2-(2-pyrimidinyl) -5-pyridyl]cyclohexanone, a key intermediate of the synthetic route, has been greatly improved. The use of Suzuki-Miyaura reaction instead of nickel catalyzed reaction avoided the anhydrous and anaerobic reaction conditions, thus made the post-treatment purification step greatly simplified compared with the existing literature. Through the optimized reaction route, the total yield of PF-04136309 reached 44.9% (based on 2-bromo-5-chloropyridine), which was largely improved compared with the existing literature, 30.2% (based on 2,5-dibromopyridine). The advantages of this synthetic route are readily available raw materials, simplified operation procedures, short reaction steps and good yields.
Key words：PF-04136309; CCR2 inhibitor; synthesis; process optimization; NMR characterization
引用本文：颜延宁，周鑫鑫. 趋化因子受体2抑制剂PF-04136309的合成研究[J]. 化学试剂，2020，42(9): 1125-1129.
新型Combretastatin A-4衍生物的合成及生物活性研究
杨超*1，钱玺丞2，周斌1，陈婷1
（1.贵州健康职业学院，贵州 铜仁 554300；2.铜仁职业技术学院 民族中兽药重点开放实验室，贵州 铜仁 554300）
摘要：Combretastatin A-4是一类结构独特的天然产物，具有较好的抗肿瘤活性。为了进一步研究该类化合物的构效关系，以3,4,5 - 三甲氧基苯甲醛和3-羟基-4-甲氧基苯乙酸为原料，在碱性条件下经缩合、酰化反应合成了5个未见文献报道的Combretastatin A-4衍生物。并通过1HNMR、13CNMR和MS对其结构进行确证。采用MTT法对合成的目标产物体外抗肿瘤活性进行了初步测定。结果表明，（E）-N-（2-（二甲氨基）乙基）-2-（3-羟基-4-甲氧基苯基）-3-（3,4,5-三甲氧基苯基）丙烯酰胺和（E）-2-（3-羟基-4-甲氧基苯基）-N-（2-（吡咯烷-1-基）乙基）-3-（3,4,5-三甲氧基苯基）丙烯酰胺对K562肿瘤细胞有较弱的抑制作用。
关键词：3,4,5-三甲氧基苯甲醛；缩合；Combretastatin A-4；合成；抗肿瘤
中图分类号：R914.5 文献标识码：A 文章编号：0258-3283（2020）--
Design and Synthesis of New Combretastatins A-4 Derivatives YANG Chao*1, QIAN Xi-cheng2, ZHOU Bin1, CHEN Ting1 (1.Guzhou College of Health Prodessions, Tongren 554300, China; 2. Key Open Laboratory of traditional Chinese Veterinary Medicine, Tongren Polytechnic College, Tongren 554300, China), Huaxue Shiji, 2020, 42( ), ～
Abstract: Combretastatin A-4 is natural product with unique structure which has been demonstrated have excellent antitumor activity. To investigate the structure-activity relationship of Combretastatin A-4, we synthesized 5 novel combretastatin A-4 derivatives (5a~5e) through condensation reaction and acylation under alkaline condition with 3,4,5-trimethoxybenzaldehyde and 3-hydroxy-4-methoxyphenylacetic acid as substrates. The compounds were characterized by 1H NMR, 13C NMR and MS. The preliminary in vitro MTT assay indicated that the products (E)-N-(2-(dimethylamino)ethyl)-2-(3-hydroxy-4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl) acrylamide and (E)-2-(3-hydroxy-4-methoxyphenyl)-N-(2-(pyrrolidin-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl) acrylamide have weak antitumor activity against K562 tumor cell line.
Key words: 3,4,5-trimethoxybenzaldehyde; condensation; combretastatin A-4;synthetic; antitumor
引用本文：杨超, 钱玺丞, 周斌, 等. 新型Combretastatin A-4衍生物的合成及生物活性研究[J]. 化学试剂, 2020, 42(9): 1130-1133.
钯催化的β-芳基化反应合成非尼布特
卢家民，李莉*
（中国医学科学院 北京协和医学院药物研究所，北京 100050）
摘要：γ-氨基丁酸的b-芳基化衍生物非尼布特通过激动GABAB受体，有增强认知、缓解紧张、减轻焦虑、恐惧、改善睡眠等作用，对其合成路线进行改善有着十分重要的意义。采用碳氢活化策略，以醋酸钯为催化剂、8-氨基喹啉为导向基团，对γ-氨基丁酸b位进行芳基化，合成γ-氨基丁酸衍生物非尼布特。利用磷酸二苄酯以及碳酸银作为反应助剂，极大地加速芳基化反应速率，相比传统的合成路线，反应步骤简洁，原子经济性高，成本较低，反应时间短，具有一定的应用前景。
关键词：碳氢活化；b-芳基化反应；钯催化反应；非尼布特
中图分类号：R914.5 文献标识码：A 文章编号：0258-3283(2020)
Synthesis of Phenibut through Pd-Catalyzed b-Arylation of C(sp3)—H Bond LU Jia-min, LI li* (Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China), Huaxue Shiji, 2020, 42(9)
Abstract：Phenibut is the derivative of γ-aminobutyric acid which is widely applied in clinic for enhancing cognition, releasing tension and anxiety disorder, improving sleep. The improvement of synthetic route of phenibut is vital. Through Pd(II)-catalyzed functionalization of unactivated C(sp3)—H bond, phenibut was synthesized by β-arylation of γ-aminobutyric acid with 8-aminoquinoline as directing group, which was followed by hydrolysis reaction of protecting group. This passage focuses on optimizing synthetic route of phenibut by using dibenzyl phosphate and silver carbonate as additives to promote catalytic cycle of Pd(OAc)2. Compared with traditional routes, this route is cheap and simple which is promising in large production.
Key words: C—H activation; β-arylation reaction; Pd-catalyzed reaction; phenibut
引用本文：卢家民，李莉. 钯催化的β-芳基化反应合成非尼布特[J]. 化学试剂, 2020, 42(9):1134-1137.
