血红素-氨基化石墨烯光催化剂的合成及其染料降解性能
李豇，韩帅，王超，师程程，殷耀兵*
(河北工程大学 材料科学与工程学院，河北 邯郸 056038)
摘要：以血红素、氧化石墨烯和尿素为原材料，通过一步水热法合成了血红素-氨基化石墨烯（H-NG）复合物。采用UV-Vis、FTIR、Raman、SEM对所合成的复合物进行结构表征，研究了该复合物对亚甲基蓝（MB）在可见光下降解反应的光催化活性。结果表明，在滴加少量H2O2条件下，0.1 g/L H-NG复合物在180 min内对10 mg/L MB的降解率达到96%；经过4次循环使用，该催化剂对MB溶液的降解率保持在92%以上，展现了较高的催化活性和良好的稳定性；通过对复合物的活性分析，对催化体系的光催化机理进行了推测。
关键词：血红素；氨基化石墨烯；尿素；过氧化物酶；光催化；亚甲基蓝
中图分类号：TQ630 文献标识码：A 文章编号：0258-3283（2020）--
Preparation of Hemin-NH2-Graphene and Its Dye Degradation Performance LI Jiang, HAN Shuai, WANG Chao, SHI Cheng-cheng, YIN Yao-bing * (College of Materials Science and Engineering, Hebei University of Engineering, Handan 056038, China), Huaxue Shiji, 2020, 42(6), ～
Abstract: Hemin-NH2-graphene (H-NG) composites were synthesized by one-step hydrothermal method using hemin, graphene oxide and urea as raw materials. The structure of the composite was characterized by UV-Vis, FTIR, Raman and SEM. The photocatalytic activity of the complex for the degradation of methylene blue (MB) under visible light was studied. The results showed that the degradation efficiency of MB(10 mg/L) by H-NG(0.1 g/L) complex in 180 min could reach 96% under the condition of adding a small amount of H2O2. The degradation efficiency of the MB solution was maintained above 88% after 4 times cycle of the catalyst, showing high catalytic activity and good stability. The photocatalytic mechanism of the catalytic system was presumed by analyzing the activity of the H-NG complex.
Key words: hemin; NH2-graphene; urea; peroxidase; photocatalytic; methylene blue
引用本文：李豇，韩帅，王超，等.血红素-氨基化石墨烯光催化剂的合成及其染料降解性能[J]. 化学试剂, 2020, 42(6):617-621.
基于三维细胞模型的氯乙基亚硝基脲耐药性研究
张黎黎，尹方正，李君，赵丽娇*，孙国辉，张娜，钟儒刚
（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）
摘要：氯乙基亚硝基脲(CENUs)是临床上重要的抗癌烷化剂，然而O6-烷基鸟嘌呤-DNA-烷基转移酶(AGT)介导肿瘤细胞对CENUs产生耐药性是其临床应用中的重要问题；设计开发AGT抑制剂作为辅药与CENUs联合使用能够有效克服CENUs的耐药性。因此，合理地评价CENUs及其联合用药策略的耐药性对于CENUs的临床应用和新药开发具有重要意义。本研究利用微孔纤维素支架培养人脑神经胶质瘤SF763细胞(AGT高表达)和SF126细胞(AGT低表达)，建立了三维肿瘤细胞模型；并将其应用于对CENUs类药物尼莫司汀(ACNU)、卡莫司汀(BCNU)和洛莫司汀(CCNU)以及CENUs与AGT抑制剂联合用药的耐药性研究。结果表明，三维肿瘤细胞对各CENUs均表现出明显的耐药性，其IC50值为传统二维细胞组的1.7～3.4倍；在CENUs与AGT抑制剂联合用药组中，虽然二维细胞组的耐药性有所下降，但三维细胞组仍然表现出了明显的耐药性。由于体外三维肿瘤球比传统二维细胞更加接近体内实体瘤的生长状态及肿瘤微环境，因此，使用三维细胞模型评价药物的耐药性有利于得到更加准确的结果，从而为体内实验提供更可靠的参考。
关键词：氯乙基亚硝基脲；三维细胞培养；神经胶质瘤细胞；耐药性；抑制剂
中图分类号：TQ469 文献标识码：A 文章编号：0258-3283（2020）
Drug Resistance of Chloroethylnitrosourea Based on a Three-dimensional Cell Model ZHANG Li-li, YIN Fang-zheng, LI Jun, ZHAO Li-jiao*, SUN Guo-hui, ZHANG Na, ZHONG Ru-gang (Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science&Bioengineering, Beijing University of Technology, Beijing 100124, China), HuaxueShiji, 2020, 42(6)
Abstract: Chloroethylnitrosoureas (CENUs) are important anticancer alkylating agents in clinics. However, the drug resistance of CENUs mediated by O6-alkylguanine-DNA-alkyltransferase (AGT) is a crucial problem in its clinical application. Designing and developing AGT inhibitors as adjuvants in combination with CENUs can effectively overcome the resistance of CENUs. Therefore, reasonable assessment of the resistance of CENUs and their combined drug strategies is of great significance for the clinical application of CENUs and the development of new drugs. In this study, a three-dimensional (3D) tumor cell model was established by culture human brain glioma SF763 cells (highly expressing AGT protein) and SF126 cells (lowly expressing AGT protein) in microporous cellulose scaffolds. The 3D cell model was used to investigate the drug resistance to CENUs, including nimustine (ACNU), carmustine (BCNU) and lomustine (CCNU), and their combination chemotherapy with AGT inhibitors. The results showed that the 3D tumor cells showed obvious drug resistance to each CENUs with IC50 values 1.49～4.18 times of the 2D cells. In the groups treated by CENUs in combination with AGT inhibitors, significant drug resistance to CENUs was observed in the 3D cell groups although it was decreased in the 2D cell groups. As the growing status and tumor microenvironment of in vitro 3D tumor spheres are more similar to those of solid tumors in vivo compared to traditional 2D cells, the application of 3D cell model will be helpful in obtaining accurate results in the evaluation of drug resistance, which will thereby provide reliable reference for in vivo experiments.
Key words: Chloroethylnitrosourea; three-dimensional cell culture; glioma cells; drug resistance; inhibitors
引用本文：张黎黎，尹方正，李君，等. 基于三维细胞模型的氯乙基亚硝基脲耐药性研究[J]. 化学试剂, 2020, 42(6):622-627.
Mild Synthesis of Metal Carbides on Few-layer Graphene from CaC2 for Efficient Oxygen Evolution Reaction
CHENG Hua-long, LV Wen-hui, YU Hai-yang, ZHANG Guo-xin*
(College of Electrical Engineering and Automation, Shandong University of Science and Technology, Qingdao 266590, China)
Abstract: Calcium carbide (CaC2) represents one fascinating material for the fabrication of carbon and metal carbides, yet high-temperature treatment was commonly used. Herein, we reported for the first time that small-sized metal carbides could be derived from CaC2 at mild conditions such as ball milling at room temperature. Ni/Fe/Co carbides were successfully demonstrated, and the underneath conversion mechanism was revealed to be redox chemistry in between reductive and oxidative metal cations (M2+). Besides, the complex redox chemistry and reconfiguration of electron-depleted C≡C dumbbells further enable the in-situ formation of highly graphitized carbon that can serve as excellent conductive substrate. Remarkably, the Ni-C-graphitic carbon composite exhibited excellent catalytic performance towards oxygen evolution reaction. Our method is believed potentially supporting the facile synthesis of other metal carbide-graphitic carbon composites as well as diverse electrochemical applications.
Key words: calcium carbide; metal carbide; carbon materials; graphene; oxygen evolution reaction
基于CaC2低温制备金属碳化物/石墨烯复合物与高效氧气析出反应性能研究
程华龙，吕文辉，于海洋，张国新*
（山东科技大学 电气与自动化工程学院，山东 青岛 266590）
摘要：碳化钙(CaC2)用于制备碳材料、金属碳化物吸引了众多研究者的关注，但通常情况下需采用高温处理。首次报道了在较低温度（室温）下，球磨CaC2与金属盐，可直接制备超小尺寸的金属碳化物。所合成的Ni、Fe、Co碳化物的转化机理为碳化钙中具有还原性
和氧化金属阳离子(M2+)之间的氧化还原反应。同时伴随复杂的氧化还原反应和哑铃状C≡C失去电荷、重构形成高石墨度的碳材料（即为石墨烯），原位形成的多层石墨烯材料可以作为良好的导电基底，用于电化学反应研究。值得注意的是，Ni-C-G复合材料表现出了优异的催化氧气析出反应性能。我们的结果可进一步支持其他金属碳化物-石墨碳复合材料的可控合成及广泛的电化学应用。
关键词：碳化钙；金属碳化物；碳材料；石墨烯；氧气析出反应
中图分类号：O611.4 文献标识码：A 文章编号：0258-3283(2020)
Citing this article: CHENG H L, LV W H, YU H Y, et al. Mild synthesis of metal carbides on few-layer graphene from CaC2 for efficient oxygen evolution reaction [J]. Huaxue Shiji, 2020, 42(6):628-635.
川芎嗪硫化氢供体衍生物的设计、合成及其抗血小板聚集活性研究
罗碧兰1，刘自兵2，李毅1，赵菊琴1，李永1，张毅1，汤磊*1，樊玲玲*1
（1. 贵州医科大学 药学院，贵州 贵阳 550004，2. 浙江海正药业股份公司，浙江 台州 318000）
摘要：依据药物化学中的活性拼接和生物电子等排原理，以4-羟基基苯乙酮和川芎嗪为原料，经取代、环化、氧化、酯化反应、醚化等反应，合成了3个川芎嗪硫化氢供体衍生物，其结构经1HNMR、13CNMR和HR-MS确证。并采用 Born 比浊法初步测试了化合物的体外抗血小板凝集活性，结果表明4-(3-硫代-3H-1,2-二硫杂环戊烯-5-基)苯基-3,5,6-三甲基吡嗪-2-甲酸酯对二磷酸腺苷 (ADP) 诱导的体外血小板聚集的抑制率IC50为1.16 mmol/L，优于阳性对照化合物川芎嗪、丁苯酞、依达拉奉和阿司匹林，是值得进一步研究的治疗心脑血管疾病的候选化合物。
关键词：川芎嗪；ADT-OH；设计；合成；抗血小板聚集活性
中图分类号: R914.5 文献标识码: A 文章编号:0258-3283（2020）
Synthesis and Anti-platelet Aggregation Activity Evaluation of Ligustrazine H2S Donor Derivatives LUO Bi-lan1, LIU Zi-bing2, LI Yi1, ZHAO Ju-qin1, LI Yong1, ZHANG Yi1, TANG Lei*1, FAN Ling-ling*1 (1. College of Pharmacy, Guizhou Medical University, Guiyang 550004, China; 2. Zhejiang Haizheng Pharmaceutical Co., Ltd., Taizhou 318000, China), Huaxue Shiji, 2020, 42(6)
Abstract: Based on the principles of the combination and bioisosterism, three ligustrazine H2S donor derivatives were designed and synthesized by substitution, cyclation, oxidation, esterification and etherification reactions using 4-hydroxyacetophenone and ligustrazine as the starting materials. The structures were confirmed by 1HNMR, 13C NMR and HR-MS. The in vitro anti-platelet aggregation activities of the target compounds have been preliminarily tested by the Born turbidimetric method，and the experimental results showed that compounds 2 (IC50 = 1.16 mmol/L) have significant inhibitory activity for adenosine diphosphate induced platelet aggregation, which is better than clinical drugs ligustrazine, 3-n-butylphthalide, edaravone and aspirin. Therefore, it may be used as a potential candidate for the treatment of cardiovascular and cerebrovascular disease.
Key words: ligustrazine; ADT-OH; design; synthesis; anti-platelet aggregation activity
引用本文：罗碧兰，刘自兵，李毅，等. 川芎嗪硫化氢供体衍生物的设计、合成及其抗血小板聚集活性研究[J]. 化学试剂，2020，42（6）:636-640.
氟代巴拉苏酰胺的色谱拆分及拆分机理研究
苏金龙，罗旭娜，方成乔，饶雨，何冠涛，林汉森*
（广东药科大学 药学院，广东 广州 510006）
摘要：建立了HPLC法对氟代巴拉苏酰胺进行手性分离，并研究其分离机理；通过考察2种不同的多糖手性固定相（CSP）（Chiralpak AD-H和Chiralcel OJ-H手性柱）、不同比例的流动相（正己烷和异丙醇），得到最佳手性分离条件，设置不同柱温得出相应的色谱参数，建立分子模型应用软件Autodock对氟代巴拉苏酰胺和手性固定相结构进行对接。结果表明，以V(正己烷)∶V(异丙醇(IPA)) = 70∶30流动相，在手性柱Chiralpak AD-H上获得最佳分离，其选择因子α为1.54，分离度Rs为6.50，且方法学验证均在合理范围内。另外，通过热力学研究和分子模拟对分离机理进行简要探讨，得出氢键和π-π相互作用是氟代巴拉苏酰胺与多糖手性固定相手性识别的重要相互作用。
关键词：氟代巴拉苏酰胺；手性固定相；分子对接；对映体分离；热力学参数；手性识别机理
中图分类号：R917 文献标识码：A 文章编号：0258-3283（2020）
Chromatographic Resolution and Chiral Recognition Mechanism of 3F-balasurbramide SU Jin-long, LUO Xu-na, FANG Cheng-qiao, RAO Yu, HE Guan-tao, LIN Han-sen* (College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China), Huaxue Shiji, 2020, 42(6)
Abstract：A high performance liquid chromatography (HPLC) method was established for chiral separation of 3F-balasurbramide. During chiral separation process, different chromatographic conditions were investigated to obtain the best separation method. Optimization of chiral separation method was conducted in two different chiral stationary phases (CSPs) and different ratio of mobile phases (n-hexane and iso-propanol). Under different conditions, better chiral separation and resolution were obtained in the organic mode with n-hexane and iso-propanol (IPA) with V(n-hexane)∶V(iso-propanol (IPA)) = 70∶30 on Chiralpak AD-H column. Enantioselectivity and resolution (α and Rs, respectively) levels with values 1.54 and 6.50, respectively. In addition, thermodynamic study and molecular simulations were also carried out to perform a brief probe into the separation mechanism, which showed that the hydrogen bonds and π‐π interactions were the major forces for chiral separation.
Key words: 3F-balasurbramide; chiral stationary phase; molecular docking; enantiomeric resolution; thermodynamics; chiral recognition mechanism
引用本文：苏金龙，罗旭娜，方成乔, 等. 氟代巴拉苏酰胺的色谱拆分及拆分机理研究[J].化学试剂, 2020, 42(6): 641-645.
1,2,3-三唑-1,3,4-噻二唑三氮烯类化合物的合成及生物活性研究
陈彦君1，张明千2，魏光璞2，龙跃*2
（1. 焦作大学 化工与环境工程学院， 河南 焦作 454003；2. 郑州大学 化学与分子工程学院， 河南 郑州 450001）
摘要：将三氮烯结构与1,3,4-噻二唑，1,2,3-三唑环结构拼接，合成16个新型目标物，并通过1HNMR、IR和LC-MS等确定其结构。通过以典型三氮烯药物达卡巴嗪（DTIC）作参照，对人胃癌细胞（MGC803）、人前列腺癌细胞（PC3）和人肝癌细胞（Hep G-2）做活性检测，结果显示部分化合物表现出较好的抑制活性，其中2-((1-(4-甲氧基苯基)-1,2,3-三唑-4-基)甲硫基)-5-(4-(3,3-二甲基三氮烯-1-基)苯基)- 1,3,4-噻二唑对人前列腺癌细胞（PC3）的IC50值为39.6 μmol/L，远低于对照药达卡巴嗪。
关键词：三氮烯；1,3,4-噻二唑；1,2,3-三唑；人胃癌细胞；人前列腺癌细胞；人肝癌细胞
中图分类号：O622.6 文献标识码：A 文章编号：0258-3283（2020）--
Synthesis and Biological Activities of 1,2,3-Triazole-1,3,4-Thiadiazole Triazene Compound CHEN Yan-jun1, ZHANG Ming-qian2, Wei Guang-pu2, LONG Yue*2 (1. Department of Chemical and Environmental Engineering, Jiaozuo Universiy, Jiaozuo 454003, China; 2. College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, China), Huaxue Shiji, 2020, 42(6), ～
Abstract: 16 novel 1,2,3-triazole-1,3,4-thiadiazole triazene derivatives were synthesized by combination of the triazene with 1,2,3-triazole, 1,3,4-thiadiazole, The structure of the compounds were determined by nucleated magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR) and mass spectrometry (LC-MS). By using the typical triazene drug dacarbazine (DTIC) as a reference, the activity detections of human gastric cancer cells (MGC803), human prostate cancer cells (PC-3) and human liver cancer cells (HepG2) were carried out. The results showed that some compounds displayed good inhibitory activity, the IC50 value of 2-(((1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)methyl)thio)-5-(4-(3,3-dimethyltriaz-1-en-1-yl)phenyl)-1,3,4-thiadiazole was 39.6 μmol/L against human prostate cancer cells (PC-3), which was far lower than the control drug dacarbazine (DTIC).
Key words: triazene; 1,3,4-thiadiazole; 1,2,3-triazole; human gastric cancer cells; human prostate cancer cells; human liver cancer cells
引用本文：陈彦君，张明千，魏光璞，等. 1,2,3-三唑-1,3,4-噻二唑三氮烯类化合物的合成及生物活性研究[J]. 化学试剂, 2020, 42(6):646-651.
槲皮素3位酰基酯的合成及抗肿瘤活性研究
姜亚玲，冯亚莉，刘金海，陈佳敏，翟广玉*
（郑州工业应用技术学院 药学与化学工程学院，河南 郑州 410021）
摘要：以廉价芦丁为原料，经苄基化保护、酸水解得到中间体7,3′,4′-O-三苄基槲皮素，中间体与羧酸发生酯化反应，再经Pd/C催化加氢脱苄基得到10种槲皮素3位酰基酯，均未见文献报道，目标产物结构经IR、 1HNMR、ESI-MS确证。采用DPPH法考察了10种目标化合物的抗氧化活性，结果显示，大部分目标化合物的SC50小于槲皮素或与槲皮素相当。采用MTT法，评价了10种目标化合物对人胃癌细胞MGC-803、人食管癌细胞EC109、人前列腺癌细胞PC-3、人食管鳞癌细胞EC9706四株肿瘤细胞的体外增殖抑制作用。结果显示，结构修饰后，目标化合物对肿瘤细胞的增殖抑制作用显著增强。
关键词：槲皮素； 衍生物； 合成； 抗氧化活性； 抗肿瘤活性
中图分类号：R914.5 文献标识码：A 文章编号：0258-3283（2020）
Synthesis and Anticancer Activity of Quercetin-3-acyl Ester JIANG Ya-ling, FENG Ya-li, LIU Jin-hai, CHEN Jia-min, ZHAI Guang-yu*1 (School of Pharmacy and Chemical Engineering, Zhengzhou university of industrial technology, Zhengzhou, 451100), Huaxue Shiji, 2020, 42(6)
Abstract: Using cheap rutin as raw material, the intermediate 7,3′,4′-O-tribenzyl quercetin was obtained through benzyl protection and acid hydrolysis. The intermediate was esterified with carboxylic acid, and then Pd/C catalytic hydrodebenzylation yielded 10 quercetin 3-acyl esters, none of which have been reported in the literature. The structure of the target product was confirmed by IR, 1HNMR, and ESI-MS. The DPPH method was used to investigate the antioxidant activity of 10 target compounds. The results showed that the SC50 of most target compounds was less than or equivalent to quercetin. The MTT method was used to evaluate the inhibitory effect of ten target compounds on the proliferation of human gastric cancer cells MGC-803, human esophageal cancer cell EC109, human prostate cancer cell PC-3, and human esophageal squamous cell EC9706. The results showed that the target compound significantly inhibited tumor cell proliferation after structural modification.
Key words: quercetin; derivatives; synthesis; antioxidant activity; antitumor activity
引用本文：姜亚玲，冯亚莉，刘金海，等. 槲皮素3位酰基酯的合成及抗肿瘤活性研究[J]. 化学试剂，2020，42（6）:652-657.
细胞工厂合成齐墩果烷型萜烯化合物的研究进展
赵雨佳1,2，范培蕾1，梁亮1，刘茵茵1，赵海波1，白净卫*2，沈正生*1
(1. 北京市计量检测科学研究院，北京 100024；2. 清华大学 药学院，北京 100084)
摘要：齐墩果烷型萜烯化合物是一类植物次级代谢产物，具有抗炎、抗氧化、抗肿瘤、保肝等功能，被广泛应用于医药、食品、农业和精细化工品行业，具有重要的应用价值。这类化合物结构复杂，难以实现化学合成。目前，主要通过从植物中提取的方式来制备。由于含量低且植物生长周期长，该制备方法耗时费力、工艺复杂，因此开发新的制备方法迫在眉睫。与植物相比，微生物具有培养周期短、能利用廉价碳源进行大规模发酵、发酵过程可以实现自动化、节约人力成本等优势，因此构建微生物细胞工厂合成齐墩果烷型萜烯类化合物是学术界和工业界的研究热点。综述该领域最新的研究进展，为构建细胞工厂合成齐墩果烷型萜烯化合物提供参考。
关键词：齐墩果烷型萜烯化合物；大肠杆菌；酿酒酵母；细胞工厂；异源合成
中图分类号：Q815 文献标识码：A 文章编号：0258-3283（2020）
Perspective on Synthesis of Oleanane-type Terpenoids in Cell Factories ZHAO Yu-jia1,2, FAN Pei-lei1, LIANG Liang1, LIU Yin-yin1, ZHAO Hai-bo1, BAI Jing-wei*2, SHEN Zheng-sheng*1 (1. Beijing Institute of Metrology, Beijing 100024, China; 2.School of Pharmacy, Tsinghua University, Beijing 100084, China), Huaxue Shiji, 2020, 42(6)
Abstract：Oleanane-type terpenoids are secondary metabolites of plants. These compounds exhibit multiple pharmaceutical activities, including anti-inflammatory, anti-oxidant, anti-tumor and liver-protection. They have been widely used in pharmacy, food, agriculture and fine chemical industries, with high value. Due to the complex structure of these compounds, it is difficult to de novo synthesis of these compounds by chemical engineering. Currently, they were produced by extraction from plants. However, the low content and the long growth period of plants limit the development of this method. It is urgency to develop a new method to produce these compounds. Compared with plants, microbes exhibit many advantages, including fast growth, auto-large-scale fermentation and labor saving. Therefore, producing oleanane-type terpenoids via the constructed microbial cell factories is a hot spot in both academic and industrial fields. In this review, we comprehensively summarize the successful cases and the strategies for de novo biosynthesizing oleanane-type terpenoids in microbes and provide new insights for the further research.
Key words：oleanane-type terpenoids; escherichia coli; saccharomyces cerevisiae; cell factories; heterogeneous synthesis
引用本文：赵雨佳，范培蕾，梁亮，等. 细胞工厂合成齐墩果烷型萜烯化合物的研究进展[J]. 化学试剂, 2020, 42(6): 658-665.
不同圆周及滤嘴通风率对卷烟主流烟气酚类成分释放量影响的气质联用分析
田海英1，张博2，楚文娟*1，李国政1，各会杰2，张峻松2
（1. 河南中烟工业有限责任公司 技术中心，河南 郑州 450000；2. 郑州轻工业大学 食品与生物工程学院，河南 郑州 450002）
摘要：为明确不同圆周及滤嘴通风率对卷烟主流烟气酚类成分释放量的影响规律。建立了主流烟气粒相物中酚类成分释放量的气相色谱质谱检测方法，并分析了圆周及滤嘴通风率对酚类释放量的影响。各酚类成分工作曲线R2在0.992~0.999之间，相对标准偏差(RSD)为3.51％~9.27％，不同水平下的加标回收率为80.5％~106.1％。相同圆周卷烟，随滤嘴通风率的增大，酚类成分释放量呈逐渐降低的趋势，其中酚类成分释放量与滤嘴通风率之间线性相关(R2＞0.9)。相同滤嘴通风率卷烟，随卷烟圆周的增大，酚类成分释放量呈逐渐增加的趋势，其中酚类成分释放量与卷烟圆周之间线性相关(R2＞0.9)。方差分析表明滤嘴通风率和卷烟圆周及两者的交互作用均对主流烟气中酚类成分释放量有显著影响。上述规律可以为烟支参数的设计提供参考。
关键词：圆周；滤嘴通风率；卷烟主流烟气；酚类成分；气相色谱质谱联用(GC/MS)
中图分类号：TS411.1 文献标识码：A 文章编号：0258-3283（2020）
Influence of Different Sizes of Cigarettes on the Release of Phenols from Mainstream Smoke TIAN Hai-ying1，ZHANG Bo2，CHU Wen-juan*1，LI Guo-zheng1，GE Hui-jie2，ZHANG Jun-song2 (1. Technology Center of Henan Tobacoo Industry Co., Ltd., Zhengzhou 450000，China；2. College of Food and Bioengineering, Zhengzhou University of Light Industry, Zhengzhou 450002, China), Huaxue Shiji, 2020, 42(6)
Abstract: In order to clarify the regularity of the amount of phenolic compounds released from mainstream cigarette smoke with different circumferences and filter ventilation rates, the simultaneous extraction method was used to extract the mainstream smoke particles and the phenolic components separated from the extract via gas chromatography mass spectrometry analysis. The same filter ventilation rate, different circumference cigarettes, phenol content: conventional cigarettes> medium fine cigarettes> fine cigarettes, phenolic content in most parts of the most significant differences between different circles; The cigarettes with the same circumference and different ventilation rate of the filter, with the increase of ventilation rate of the filter, the release of phenolic components were gradually reduced, and the content of phenolic compounds in most filter vents were extremely significant. The contents of the 15 phenolic compounds in the mainstream smoke particle phase were phenol, 2-methoxyphenol, 2,4-dimethylphenol, p-cresol, 2,5-dimethylphenol, 4-ethylguaiacol. The above results can provide a reference for the design of cigarette parameters.
Key words: circumference; filter ventilation; mainstream smoke; phenolic compounds; gas chromatography-mass spectrometry
引用本文：田海英，张博，楚文娟, 等. 不同圆周及滤嘴通风率对卷烟主流烟气酚类成分释放量的影响的气质联用分析[J]. 化学试剂, 2020, 42(6): 666-672.
新型离子电极用于煤基甲醇溶液中微量铬测定
李吉辉
（神华榆林能源化工有限公司，陕西 榆林 719319）
摘要：煤基甲醇制烯烃是以煤为原料合成甲醇，然后通过甲醇制取低碳烯烃。以煤代油生产低碳烯烃是实现中国能源战略，保证国家能源安全的重要途径之一。近年来，煤基甲醇制烯烃技术在我国得到了快速发展和应用，煤基甲醇根据其不同的工艺特性，产品甲醇溶液中存在的微量铬等重金属离子严重影响煤基甲醇制烯烃催化剂的使用性能。以乙基香兰素和1,3-二氨基硫脲合成的席夫碱乙基香兰素缩-1,3-二氨基硫脲为中性载体，将其与碳粉混合，以液体石蜡为粘合剂，制备了新型的铬(Ⅲ)离子电极。室温下，以饱和甘汞电极作参比电极，离子电极作指示电极，对煤基甲醇中的Cr3+进行测定，取得了较好的结果。
关键词：离子电极；乙基香兰素缩-1,3-二氨基硫脲；铬（Ⅲ）；煤基甲醇；甲醇制烯烃
中图分类号：O6 文献标识码：A 文章编号：0258-3283(2020)
New Ion Electrode for Determination of Trace Chromium in Methanol Based on Coal LI Ji-hui (Shenhua Yulin Energy Chemical Co., Ltd, Yulin 719319, China), Huaxue Shiji, 2020, 42(6)
Abstract: Methanol based on coal to olefins, is always synthed the methanol from the ocal, thento low-carbon olefin. Production of low-carbon olefins using coal instead of oil, which is realizing china's energy strategy of coal for oil, is one of theimportant ways to ensure national energy security. In recent years, the alternative route for the production of methanol from coal as a raw material to produce olefins has been highly valued by academic and industrial circles in China. Because of the differentiation processes of coal-based methanol, there are different trace presence of heavy metal, such as chromium, et al, which influence the performance of catalyst of coal-based methanol to olefin seriously. A sensitive film of carbon paste doped with ethyl vanillin-1,3-diamino-2-thiourea which was synthesized using the rection of ethyl vanillin with 1,3-diamino-2-thiourea as a film carrier, was prepared and investigated as a new Cr(III)-selective electrode. At room temperature, it was used as indicator electrode, with the saturated calomel electrode as reference electrode. The chromium in methanol solution based on coal was tested using this electrode, and got the good result.
Key words: ion electrode; ethyl vanillin-1,3-diamino-2-thiourea; chromium(III); methanol based on coal; methano to olefins
引用本文：李吉辉. 新型离子电极用于煤基甲醇溶液中微量铬测定[J].化学试剂， 2020, 42（6）:673-676.
光谱法研究呋喃妥因与牛血清白蛋白的相互作用
赵刚*，胡雪健，何茜，黄曦瑶
（渤海大学 化学化工学院，辽宁 锦州 121013）
摘要：呋喃妥因（NFT）属于硝基呋喃类抗生素，由于其具有遗传毒性和致癌性，已被许多国家列为禁药。采用荧光光谱法、紫外-可见光谱法和同步荧光光谱法等研究了NFT和牛血清白蛋白（BSA）之间相互作用机制。实验结果表明：NFT对BSA的荧光猝灭主要为静态猝灭；25 ℃时二者的结合常数与结合位点数分别为6.02×104 L/mol和1.28；热力学参数焓变（ΔH）与熵变（ΔS）分别为-101.3 kJ/mol和-0.28 J/(mol•K)，说明NFT与BSA之间的作用力主要为范德华力和氢键；位点竞争实验结果表明NFT结合在BSA亚结构域Ⅱ A的位点Ⅰ。紫外光谱法和同步荧光光谱法实验结果表明，NFT诱导BSA的构象发生变化。
关键词：呋喃妥因；牛血清白蛋白；荧光光谱法；紫外-可见光谱法；相互作用
中图分类号：O657.3 文献标识码：A 文章编号：0258-3283（2020）--
Study on the Interaction between Nitrofurantoin and Bovine Serum Albumin ZHAO Gang* , HU Xue-jian, HE Qian, HUANG Xi-yao (College of Chemistry and Chemical Engineering, Bohai University, Jinzhou 121013, China), Huaxue Shiji, 2020, 42(6), ～
Abstract：Nitrofurantoin (NFT) is a nitrofuran antibiotic. It has been banned in many countries due to its genetic toxicity and carcinogenicity. The interaction mechanism between NFT and bovine serum albumin (BSA) was studied by fluorescence spectroscopy, UV-visible spectroscopy, synchronous fluorescence spectroscopy, time resolved fluorescence spectroscopy. The results showed that the BSA fluorescence quenching was mainly static quenching by NFT. The binding constant and the number of binding sites were 6.02×104 L/mol and 1.28 at 25 ℃. The enthalpy change (ΔH) and entropy (ΔS) were -101.3 Kj/mol and -0.28 J/(mol•K), which indicated that the forces were van der Waals forces and hydrogen bonds between NFT and BSA. The results of site competition experiments showed that NFT binds to BSA Site Ⅰ (subdomain II A). The results of UV-vis spectroscopy and synchronous fluorescence spectroscopy showed that the BSA conformation changed induced by NFT .
Key words：nitrofurantoin; bovine serum albumin; fluorescence spectroscopy; UV-vis spectroscopy; interaction
引用本文：赵刚，胡雪健，何茜，等. 光谱法研究呋喃妥因与牛血清白蛋白的相互作用[J]. 化学试剂，2020，42(6):677-680.
黑龙江大庆地区野生与仿野生栽培蒙古黄芪的品质研究
刘淑霞1, 2，魏国江1，郭永霞2，徐海军1，单仁奕2，张旭1，关向军*1
(1.黑龙江省科学院 大庆分院，黑龙江 大庆 163319；2. 黑龙江八一农垦大学，黑龙江 大庆 163319)
摘要：通过对黑龙江省大庆市星火牧场草甸上野生蒙古黄芪和大同区仿野生栽培蒙古黄芪中皂苷类和黄酮类成分的分析比较，评价仿野生栽培蒙古黄芪与野生蒙古黄芪的品质差异。采集10批野生和20批仿野生栽培蒙古黄芪样品，采用 UPLC—ELSD法测定毛蕊异黄酮苷、芒柄花苷、毛蕊异黄酮、芒柄花素、黄芪皂苷 I、黄芪皂苷II、黄芪皂苷III和黄芪皂苷IV共计8种成分。结果表明：供试的4～5年生仿野生栽培蒙古黄芪中黄酮总量、皂苷总量、毛蕊异黄酮苷、芒柄花苷、黄芪皂苷 I、黄芪皂苷II和黄芪皂苷III的量高于野生黄芪，芒柄花素和黄芪皂苷 IV的量低于野生黄芪；通过研究发现，仿野生栽培1～5年生黄芪中8种成分中黄酮类成分随着黄芪生长年限的增长出现不断增高的趋势，而皂苷类成分出现降低趋势。
关键词：蒙古黄芪；皂苷；黄酮；品质；栽培
中图分类号: R286.02 文献标识码: A 文章编号: 0258-3283（2020）
Quality Analysis of Semi-cultivated and Wild Astragalus Membranaceus Var. Mongholicus from Daqing District in Heilongjiang Province LIU Shu-xia1,2, WEI Guo-jiang1, GUO Yong-xia2, XU Hai-jun1, SHAN Ren-yi2, ZHANG Xu1, GUAN Xiang-jun*1 (1. Daqing Branch of Heilongjiang Academy of Sciences, Daqing 163319, China; 2. Heilongjiang Bayi Agricultural University, Daqing 163319, China), Huaxue Shiji, 2020, 42(6)
Abstract: In order to evaluate the quality of semi-cultivated astragalus membranaceus var. mongholicus, the contents of flavonoids and saponins between the semi-cultivated and wild astragalus membranaceus var. mongholicus were determined in Daqing district in Heilongjiang province. 10 Wild samples and 20 semi-cultivated samples of astragalus membranaceus var. mongholicus were collected from Daqing Spark meadow and Datong area respectively. The contents of calycosin, glucoside, ononin, calycosin, formononetin, astragalosides I, astragalosides II, astragalo -sides III, and astragalosides IV were analyzed by UPLC-ELSD. The average contents of calycosin glucoside, ononin, astragalosides I, astragalosides II, and astragalosides III in four or five-year semi-cultivated samples were higher than the wild samples. Whereas the content of formononetin and astragaloside IV in semi-cultivated samples were less than the wild samples. We found that the contents of flavonoids increased as the years increasing in one to five-year semi-cultivated samples of astragalus membranaceus var. mongholicus, while the content of saponins were lower as the years increasing in the growth period.
Key words: astragalus membranaceus var. mongholicus; saponins; flvonoids; cultivate
引用本文：刘淑霞，魏国江，郭永霞，等. 黑龙江大庆地区野生与仿野生栽培蒙古黄芪的品质研究[J].化学试剂，2020, 42（6）:681-685.
高效液相色谱法测定VMCPP薄膜中芥酸酰胺的含量
杨璐，周国桁，刘容宏，付金贝，秘铭，孙元浩，许超*
（山东省产品质量检验研究院 山东省材料化学安全检测技术重点实验室，山东 济南 250102）
摘要：采用高效液相色谱法（HPLC）测定了真空镀铝聚丙烯薄膜（VMCPP）中芥酸酰胺的含量。芥酸酰胺在25～250 mg/L范围内线性良好，相关系数R＞0.999，检出限为0.2 mg/L，定量限为1 mg/L。外标法具有良好的稳定性和灵敏度。对比了4种样品提取溶剂的提取效果，选择环己烷作为提取溶剂，并从回流时间、回流次数两个方面对提取方法进行了优化。对比分析了5个国内外芥酸酰胺的检测标准和本试验方法的差异，指出更具包容性的检测标准是未来发展的趋势，这些相近的检测标准可以促进检测技术的国际交流，扩大知识与科学的合作。
关键词：芥酸酰胺；高效液相色谱；真空镀铝聚丙烯薄膜；回流提取；标准
中图分类号：TQ 文献标识码:A 文章编号：0258-3283（2020）
Determination of Erucamide in Vacuum Aluminized Polypropylene Film (VMCPP) by High-Performance Liquid Chromatography YANG Lu, ZHOU Guo-heng, LIU Rong-hong, FU Jin-bei, MI Ming, SUN Yuan-hao, XU Chao* (National Supervision and Inspection Center for Packaging Product Quality (Jinan), Shandong Institute Product Quality Inspection, Jinan 250102, China), Huaxue Shiji, 2020, 42(6)
Abstract: The content of erucamide in vacuum aluminized polypropylene film (VMCPP) was tested by high-performance liquid chromatography (HPLC). Erucamide was well linear in the range of 25～250 mg/L, correlation coefficient: R＞0.999, detection limit: 0.2 mg/L, quantitative limit: 1 mg/L. The external calibration had good stability and sensitivity. The extraction effects of 4 extraction solvents were compared, and cyclohexane was chosen as the extraction solvent. The extraction method was optimized from two aspects: reflux time and reflux times. By comparing and analyzing the differences between the five domestic and international test standards of erucamide and the method in this paper, it was revealed that the more inclusive of test standards was the trend of future development, and these similar test standards can promote international exchange of test technologies and expand cooperation in knowledge and science.
Key words: Erucamide; High performance liquid chromatography; Vacuum aluminized polypropylene film; reflux extraction; standard
引用本文：杨璐，周国桁，刘容宏，等. 高效液相色谱法测定VMCPP薄膜中芥酸酰胺的含量[J]. 化学试剂, 2020, 42(6):686-690 .
库仑滴定法快速测定吡拉西坦的含量研究
牛鹤丽1，张春波*2
（1. 白城医学高等专科学校，吉林 白城 137000；2. 延边大学 理学院，吉林 延吉 133000）
摘要：利用库仑滴定法快速测定吡拉西坦的含量。铂片电极分别作电解电极对和指示电极对，0.8 mol/L溴化钾（pH 9.0）为支持电解质溶液，经20.00 mA恒电流电解生成BrO-后，与预处理后的样品溶液中NH4+定量发生氧化还原反应，记录电解至滴定终点时间，根据法拉第电解定律，计算样品中吡拉西坦的含量。利用该方法分别测定不同厂家的样品，结果与HPLC法和凯氏定氮法相近，无显著性差异(P>0.05)，且相对标准偏差均低于1.60%，同时该方法操作简便、快速，因而适于吡拉西坦的质量检测。
关键词：吡拉西坦；库仑滴定；含量测定；溴化钾；质量控制
中图分类号：O657.12 文献标识码：A 文章编号：0258-3283（2020）--
Determination of the Content of Piracetam by Coulometric Titration Niu He-li1, Zhang Chun-bo*2(1. Baicheng Medical College, Baicheng 137000, China; 2. College of science, Yanbian University, Yanji 133000, China), Huaxue Shiji, 2020, 42(6), ～
Abstract: A novel method that coulometric titration to rapid determine content of piracetam is described. Two couple of platinum electrode were served as working electrode pairs and indicating electrode pairs respectively, 0.8 mol/L potassium bromide solution (pH 9.0) act as the support electrolyte solution, and intensity of constant current is 20.00 mA. The BrO- was electrolytic generated by the potassium bromide solution electrolysis react with the NH4+ in the pretreatment sample solution, which was quantitative oxidation-reduction reaction. The result is obtained by Faraday’s law through recording time that titrated to titration end-point. The piracetam of three brands were seperately measured by coulometric titration, HPLC method, and kjeldahl method. The results showed that the three methods result have no significant difference (P>0.05), and the relative standard deviations of coulometric titration result were lower than 1.60 %. Meanwhile, with merit of simplicity, convenience, rapid and highly automation, et al, the proposed method will be very useful for the piracetam content determination.
Keywords: piracetam; coulometric titration; content determination; potassium bromide; quality control
引用本文：牛鹤丽，张春波. 库仑滴定法快速测定吡拉西坦的含量研究[J]. 化学试剂, 2020, 42(6):691-693.
嘧啶并萘酰亚胺Ag+荧光探针的合成及性能研究
周五，吴爱斌*
（长江大学 化学与环境工程学院，湖北 荆州 434023）
摘要：以4-硝基-1,8-萘酐为起始原料，经硝化、还原和亲核加成制得N-丁基-4,5-二氨基-1,8-萘酰亚胺，继而与2-呋喃甲醛缩合得到目标化合物嘧啶并萘酰亚胺衍生物，其结构经1H NMR、13C NMR、HR-MS和元素分析确证。光谱研究表明，目标化合物对Ag+具有较好的选择性和适中的响应时间，在502 nm处发生荧光猝灭，荧光强度与银离子浓度的关系为y = -4.64873x + 392.331，检测限为1.56´10-6 mol/L。
关键词：萘酰亚胺；荧光探针；2-呋喃甲醛；银离子；合成
中图分类号：O626.4 文献标识码：A 文章编号：0258-3283(2020)--
Synthesis and Properties of Pyrimidine Naphthalimide-based Ag+ Fluorescent Probes ZHOU Wu, WU Ai-bin * (School of Chemistry and Environmental Engineering, Yangtze University, Jingzhou 434023, China)
Abstract：4-nitro-1,8-naphthalene anhydride was used as raw material to prepare N-butyl-4,5-diamino-1,8-
naphthalimide (compound 4) by nitration, reduction and nucleophilic addition reaction, and then, the condensation reaction of compound 4 with furaldehyde was performed to obtain the pyrimido-naphthylimide derivative (compound 5). The structure of the title compound was confirmed by 1H NMR, 13C NMR, HRMS and elemental analysis. Optical studies showed that compound 5 has good selectivity and proper response time for Ag+ and the fluorescence quenched at 502 nm. The relationship between fluorescence intensity and Ag+ concentration was y = -4.64873x + 392.331, and the detection limit was 1.56´10-6 mol/L.
Key words：naphthalimide; fluorescence probe; 2-furaldehyde; silver ion; synthesis
引用本文：周五，吴爱斌. 嘧啶并萘酰亚胺Ag+荧光探针的合成及性能研究[J]. 化学试剂, 2020, 42(6):694-698.
反相微乳法制备羟基磷灰石纳米晶体
毛春玲，刘雅茹，吴孟霏，孙玉琦*
（锦州医科大学 药学院，辽宁 锦州 121001）
摘要：采用反相微乳法制备羟基磷灰石纳米晶体，以正己烷为有机相、水为水相、CTAB与正己醇为乳化剂和助乳化剂，通过三元体系三相图优化各组分的比例。CaCl2 与Na2HPO4为反应物，通过电导率确定反应物的浓度。并对所制备样品的钙含量、制剂学性质和体外释放行为进行考察。结果表明采用反相微乳法制备羟基磷灰石纳米晶体工艺可行，m（有机相）：m（乳化剂相）=1:1，m（CTAB）：m（正己醇）=1:2。 0.12 mol/L的Na2HPO4与同体积0.2 mol/L的CaCl2反应，所制备样品为羟基磷灰石纳米晶体，样品粒径较小，并具有较好的制剂学性质和体外释放行为。
关键词： 羟基磷灰石纳米晶体；反相微乳法；三相图；电导率；制备与表征
中图分类号：R944 文献标识码： A 文章编号：0258-3283（2020）
Preparation of Hydroxyapatite Nanocrystal by Reverse Microemulsion Method MAO Chun-ling, LIU Ya-ru, WU Meng-fei, SUN Yu-qi* (Colloge of Pharmacy, Jinzhou Medical University, Jinzhou 121001, China), Huaxue Shiji, 2020,42(6)
Abstract: N-Hexane (organic phase), CTAB (emulsifier), n-hexanol (co-emulsifier) and CaCl2, Na2HPO4 (reactants) were used to prepare hydroxyapatite nanocrystal by a reverse microemulsion method. The three-phase diagrams of ternary system and conductivity were used to optimize the composition and concentration. The calcium contents, pharmaceutical properties and release behavior of the samples had been investigated. The results showed that it was feasible to prepare hydroxyapatite nanocrystal by a reverse microemlsion method. The mass ratio of organics-emulsifier phase and CTAB-n-hexanol was 1:1 and 1:2, respectively. Na2HPO4 (0.12 mol/L) reacted with equal volumes of CaCl2 (0.2 mol/L) to generate hydroxyapatite. The sample was confirmed as hydroxyapatite nanocrystal. It had better pharmaceutical properties and release behavior with smaller particle size.
Key words: hydroxyapatite nanocrystal; reverse microemulsion method; three-phase diagrams; conductivity; preparation and characterization
引用本文：毛春玲，刘雅茹，吴孟霏, 等. 反相微乳法制备羟基磷灰石纳米晶体[J]. 化学试剂, 2020, 42(6):699-703.
星点设计效应面法优选超声提取石菖蒲挥发油的工艺研究
杨丽霞，王颖莉*
（山西中医药大学 中药与食品工程学院，山西 晋中 030619）
摘要：通过星点设计效应面法优选超声提取石菖蒲挥发油的工艺。采用超声提取法提取石菖蒲挥发油，以挥发油得率（%）及β-细辛醚含量（mg/g）为指标，以三因素五水平星点设计考察料液比、超声时间和超声功率对提取工艺的影响，运用效应面法优选石菖蒲中挥发油的超声提取工艺，并进行预测分析和验证试验。评价指标的二项式拟合方程（r= 0.9357）优于多元线性回归方程（r=0.8892），优选的提取工艺为料液比0.08 g/mL、超声时间36.56 min、超声功率181.64 W，此条件下挥发油得率为5.89%，挥发油中β-细辛醚的含量为39.80%。星点设计效应面法优选的石菖蒲挥发油超声提取工艺稳定可行，具有良好的预测性。可用于石菖蒲挥发油工业化生产。
关键词：石菖蒲；挥发油；星点设计效应面法；超声提取；β-细辛醚
中图分类号：R284.2 文献标识码：A 文章编号：0258-3283（2020）
Optimization of Ultrasonic Extraction of Volatile Oil from Acorus Tatarinowii Rhizoma by Central Composite Design-response Surface Method YANG Li-xia, WANG Ying-li* (Institute of Pharmaceutical and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong 030619,China), Huaxue Shiji, 2020, 42(6)
Abstract： The best extraction technology of volatile oil from Acorus tatarinowii Rhizoma was selected by central composite design-response surface method. Ultrasonic extraction was used to extract the volatile oil of Acorus tatarinowii Rhizoma, the yield of volatile oil (%) and the content of β-asarone (mg/g) were taken as the indexes. The influence of the ratio of material to liquid, ultrasonic time and ultrasonic power on the extraction process was investigated by central composite design of three factors and five levels. The technology of ultrasonic extraction of volatile oil from Acorus tatarinowii Rhizoma was optimized by response surface method, and the prediction analysis and verification test were carried out. Multiple correlation coefficients from second-order polynomial equation(r＝0.9357)were prior to those from multilinear equation(r＝0.8892), optimum extraction process was 0.08 g/mL of the ratio of material to liquid, 36.56 min of ultrasonic time, 181.64 W of ultrasonic power. Under this condition, average yield of volatile oil was 5.89%,content of β-asarone was 39.80% in volatile oil. The optimized extraction process of central composite design-response surface method is stable and feasible, and can be used for industrial production of volatile oil of Acorus tatarinowii Rhizoma.
Key words：Acorus tatarinowii Rhizoma; volatile oil; central composite design-response surface method; ultrasonic extraction; β-asarone
引用本文：杨丽霞，王颖莉. 星点设计效应面法优选超声提取石菖蒲挥发油的工艺研究[J].化学试剂，2020，42（6）：704-708.
MoO3/SiO2催化合成咪唑并[1,2-a]吡啶化合物
杨泽熙，马晓明，刘建武，严生虎，张跃*
（常州大学 制药与生命科学学院，江苏 常州 213164）
摘要：本文研究了用负载型MoO3/SiO2固体酸催化Groebke-Blackburn-Bienaymé（GBB）三组分反应合成一系列咪唑并[1,2-a]吡啶化合物。选用的反应底物为芳香醛、不同取代基的2-氨基吡啶以及TMSCN。主要考察了催化剂的负载量、底物物质的量比、反应温度以及反应时间对产物收率的影响。产物结构经红外、质谱、1H NMR和13C NMR表征，确定了咪唑并[1,2-a]吡啶化合物合成的最佳温度为80 ℃、最佳反应时间为1 h、最佳反应底物物质的量比为1∶1.2∶1以及负载型MoO3/SiO2固体酸催化剂负载量为20 mol%时催化效果最好。负载型MoO3/SiO2固体酸催化剂具有催化活性高、反应条件温和。
关键词：MoO3/SiO2固体酸催化剂；Groebke-Blackburn-Bienaymé反应；咪唑并[1,2-a]吡啶化合物；芳香醛；2-氨基吡啶；TMSCN
中图分类号：TQ20 文献标识码：A 文章编号：0258-3283（2020）
Synthesis of Imidazole[1,2-a]Pyridine Compounds Using MoO3/SiO2 Solid Acid Catalyst YANG Ze-xi, MA Xiao-ming, LIU Jian-wu, YAN Sheng-hu, ZHANG Yue* (School of pharmacy and Life Sciences, Changzhou University, Changzhou 213164, China), Huaxue Shiji, 2020, 42(6)
Abstract: A series of imidazo[1,2-a]pyridine compounds were synthesized by the three component reaction of Groebke-Blackburn-Bienayme (GBB) catalyzed by supported MoO3/SiO2 solid acid. Several aromatic aldehydes, 2-aminopyridine with different substituents and TMSCN were selected as reaction substrates. The effects of catalyst loading, molar ratio of substrate, reaction temperature and reaction time on the yield of the product were investigated. The structure of the products were confirmed by IR, MS, 1H NMR and 13C NMR. The optimum temperature, reaction time, molar ratio of substrate and supported MoO3 / SiO2 solid acid catalyst were 80 ℃, 1 h, 1:1.2:1 and 20 mol% respectively. At last, it was concluded that the supported MoO3 / SiO2 solid acid catalyst had high catalytic activity and mild reaction conditions.
Key words: MoO3/SiO2 solid acid catalyst; Groebke-Blackburn-Bienaymé reaction; imidazole[1,2-a]pyridine derivatives; aromatic aldehyde; 2-aminopyridine; TMSCN
引用本文：杨泽熙, 马晓明, 刘建武, 等. MoO3/SiO2催化合成咪唑并[1,2-a]吡啶化合物[J]. 化学试剂, 2020, 42(6):709-715.
微波辅助L-脯氨酸催化合成吡唑并[1,2-b]酞嗪-5,10-二酮
雷英杰*1，丁玫1，姚庆佳2
（1. 天津理工大学 化学化工学院，天津 300384；2. 天津市斯芬克司药物研发有限公司，天津 300457）
摘要：含吡唑并[1,2-b]酞嗪-二酮分子片段的杂环具有良好的抗炎、解热镇痛和抗缺氧等活性，因此，探讨和优化绿色高效的合成方法是酞嗪及其衍生物研发的热点。基于L-脯氨酸作为有机催化剂具有无毒无害和水溶性好等特点，结合微波辐射的快速、高效等优势，以芳香醛、丙二腈(或氰乙酸乙酯)和邻苯二甲酰肼为原料，乙醇/水为溶剂，催化剂用量15 mol%，微波功率300 W和80 ℃的条件下，通过成环缩合反应“一锅法”制备得到目标化合物，合成收率达86% ～ 95%。该方法具有条件温和、操作简单以及环境友好等优点。
关键词：吡唑并[1,2-b]酞嗪-5,10-二酮；合成；L-脯氨酸；微波辐射；一锅法
中图分类号：O643 文献标识码：A 文章编号：0258-3283（2020）
Microwave-assisted L-Proline Catalyzed Synthesis of 1H-Pyrazolo[1,2-b]phthalazine-5,10-diones LEI Ying-jie1, DING Mei1, YAO Qing-jia2 (1. School of Chemistry & Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China; 2. Sphinx Scientific Laboratory Corporation, Tianjin 300457, China), Huaxue Shiji, 2020, 42(6)
Abstract: Heterocycles containing a pyrazolo[1,2-b]phthalazine-dione moiety are of current interest due to their biological activities such as anti-inflammatory, analgesic and antihypoxic activities. Therefore, the development of a green, easy efficient method for the preparation demands serious attention. In view of L-proline’s remarkable ability to catalyze organic transformation with non-toxic, harmless and water-soluble characteristics, along with the fast and significant efficiency of microwave-promoted in green chemistry, several pyrazolo[1,2-b]phthalazine-5, 10-dione derivatives (4a～4l) were synthesized from the aromatic aldehydes with malononitrile (or ethyl cyanoacetate) and phthalhydrazide by the one-pot cyclocondensation reaction in a mixed solvent of ethanol and water mediated by L-proline with the amount of 15 mol% under microwave irradiation at 300 W with a temperature of 80 ℃ under with good yields of 86%～95% respectively. The reaction reveals this procedure mild reaction condition, easy work-up and environmentally benign nature.
Keywords: pyrazolo[1,2-b]phthalazine-5,10-dione; synthesis; L-proline; microwave irradiation; one-pot method
引用本文：雷英杰，丁玫，姚庆佳. 微波辅助L-脯氨酸催化合成吡唑并[1,2-b]酞嗪-5,10-二酮[J]. 化学试剂，2020, 42（6）:716-721.
克立硼罗合成工艺研究
王启帅，骆训邦，朱宽，刘海城*
（扬子江药业集团，江苏 泰州 215212）
摘要：优化磷酸二酯酶-4（PDE4）抑制剂克立硼罗的合成工艺。以2-溴-5-羟基苯甲醛和对氟苯腈为起始原料，经过取代、还原、酯化、硼化、环合等五步反应得到目标化合物。目标化合物结构经1HNMR及13CNMR谱确证，路线总收率为34.5%（以2-溴-5-羟基苯甲醛计），纯度达到99.9%以上（HPLC法）。合成方法原料易得、操作简单、产品纯度高，适合工业化生产。
关键词：磷酸二酯酶-4抑制剂；原料药；特应性皮炎；克立硼罗；合成工艺；工业生产
中图分类号：R9 文献标识码： A 文章编号：0258-3283(2020)—
Study on the synthetic process of crisaborole WANG Qi-shuai, LUO Xun-bang, ZHU Kuan, LIU Hai-cheng* (Yangzijiang Pharmaceutical Co., Ltd. taizhou 215212, China), Huaxue Shiji, 2020, 42(6), ～
Abstract: Objective: To optimize the synthesis process of Cleborone, a phosphodiesterase-4 (PDE4) inhibitor. Method: Using 2-bromo-5-hydroxybenzaldehyde and p-fluorobenzonitrile as starting materials, Cleborone was obtained through five steps of substitution, reduction, esterification, boronization, and cyclization. Results and conclusion: The target structure was confirmed by 1H-NMR and 13C-NMR spectra. The total yield of the route was 34.5% (based on 2-bromo-5-hydroxybenzaldehyde), and the purity was above 99.9% (HPLC method). The synthesis method uses cheap raw materials, simple operation and high product purity, and is suitable for industrial production.
Key words: phosphodiesterase-4 inhibitor; API; Atopic dermatitis; Crisaborole; synthetic process; industrial production
引用本文：王启帅，骆训邦，朱宽，等. 克立硼罗合成工艺研究[J]. 化学试剂, 2020, 42(6):722-725.
多靶点酪氨酸激酶抑制剂lenvatinib的合成工艺优化
吴露婷，范为正，冯柏年*
(江南大学 药学院，江苏 无锡 214122）
摘要：多靶点酪氨酸激酶抑制剂lenvatinib合成路线的改进。2-甲氧基-4-氨基苯甲酸甲酯与丙二酸环(亚)异丙酯缩合后，经环合、氯代及氨解制得4-氯-7-甲氧基喹啉-6-甲酰胺。以4-氨基-3-氯苯酚为原料，与4-氯-7-甲氧基喹啉-6-甲酰胺发生亲核取代生成4-(4-氨基-3-氯苯氧基)-7-甲氧基喹啉-6-甲酰胺，接着与环丙胺在N, N-羰基二咪唑的作用下发生成脲反应得到目标化合物lenvatinib，总收率为50.4%（以2-甲氧基-4-氨基苯甲酸甲酯计，文献为39%），纯度99.5%。目标化合物的结构经1HNMR和ESI-MS确证。相比于文献路线，方法采用了更加安全环保的试剂进行合成，降低了生产成本，减少了反应步骤，提高了收率，具有一定的工业化应用前景。
关键词：lenvatinib；多靶点；酪氨酸激酶抑制剂(TKI)；抗肿瘤；喹啉；合成
中图分类号：R914 文献标识码：A 文章编号：0258-3283（2020）--
Improved Synthesis of Multi-target Tyrosine Kinase Inhibitor Lenvatinib WU Lu-ting, FAN Wei-Zheng, FENG Bai-nian*(School of Pharmacy, Jiangnan University, Wuxi 214122, China), Huaxue Shiji, 2020, 42(6), ～
Abstract: The synthesis of multi-target tyrosine kinase inhibitor lenvatinib was optimized. 4-Chloro-7-methoxyquinoline-6-carboxamide (7) was synthesized with methyl 4-amino-2-methoxybenzoate (2) and Isopropylidene malonate (3) as raw material, through condensation, ring closure, chlorination and aminolysis. The target compound lenvatinib was obtained starting from 4-Amino-3-chlorophenol (8) and compound 7 through 2 steps including nucleophilic substitution and the urea reaction with an overall yield of 50.4% (based on compound 2) and an HPLC purity of 99.5%. The structure of lenvatinib was confirmed by 1HNMR and ESI-MS. Compared with the literature route, the method uses safer and more environmentally friendly reagents which reduces production cost , reduces reaction steps, improves the yield and it is more suitable for industrial production.
Key words: lenvatinib; multi-target; TKI; antitumor; quinoline; synthesis
引用本文：吴露婷，范为正，冯柏年. 多靶点酪氨酸激酶抑制剂lenvatinib的合成工艺优化[J]. 化学试剂，2020, 42(6): 726-730.
3-苯氧基溴丙烷的合成
张宁1，张宗磊1，郭亚芸2，段崇刚1，杨利1，孔祥雨*1
（1. 山东省药学科学院 山东省化学药物重点实验室，山东 济南 250101；2. 山东省葡萄研究院，山东 济南 250100）
摘要：改进了阿地溴铵中间体标题化合物的合成工艺。以苯酚和3-溴-1-丙醇为起始原料，经亲核取代、酯化、溴代三步反应得到标题化合物，其中3-苯氧基对甲苯磺酸丙酯不经柱层析直接利用乙酸乙酯和石油醚重结晶得到纯品（HPLC>98%），工艺总收率73.1%，产品纯度>98%，产品结构经1HNMR确证。改进后的工艺操作简单、成本低廉、反应条件温和，适合工业化生产，为标题化合物的合成提供了一种新的、高效的制备方法。
关键词：阿地溴铵；支气管痉挛；3-苯氧基溴丙烷；合成；工艺改进
中图分类号：O625.31 文献标识码：A 文章编号：0258-3283(2020)--
Synthesis of 3-Phenoxypropyl bromide ZHANG Ning1, ZHANG Zong-lei1, GUO Ya-yun2, DUAN Chong-gang1, YANG Li1, KONG Xiang-yu1*(1. Key Lab for Chemical Drug Research of Shandong Province, Shandong Academy of Pharmaceutical Science, Jinan 250101, China; 2. Shandong Academy of Grape, Jinan 250100, China), Huaxue Shiji, 2020, 42(6), ～
Abstract: The synthesis 3-Phenoxypropyl bromide, a key intermediate of aclidinium bromide was improved. 3-Phenoxypropyl bromide was syhthesized by a three-step reaction of nucleophilic substitution, esterification、bromination from phenol and 3-Bromo-1-propanol. then the purity of 3-Phenoxypropyl-4-methylbenzene sulfonate (HPLC>98%) was recrystallized directly with petroleum ether and ethyl acetate without purifying by column chromatography. Then, in overall yield of 73.1% and >98% purity. The structures of product was characterized by 1H NMR . The improved reaction condition was easy to operating, low cost, and easy to be scaled up in industrialization, providing a new and efficient mehod for synthesis of key intermediate of 3-Phenoxypropyl bromide.
Key words: aclidinium bromide; 3-Phenoxypropyl bromide; synthesis
引用本文：张宁, 张宗磊，郭亚芸，等. 3-苯氧基溴丙烷的合成[J]. 化学试剂, 2020, 42(6): 731-734.
花椒毒醇、花椒毒素与欧前胡素的合成
王悦秋，梁大伟*，李小梅，叶群丽
(雅安职业技术学院 药学与检验学院，四川 雅安 625000)
摘要：花椒毒醇、花椒毒素与欧前胡素为香豆素类天然活性分子。以2,6-二羟基苯乙酮与溴代乙醛缩二乙醇为原料，经单酚羟基缩合、成环构建呋喃片段，然后在硫酸催化下与苹果酸经Pechmann缩合反应成吡喃-2-酮骨架，进一步经Baeyer-Villiger氧化合成花椒毒醇，4步总收率为42%，最后分别与碘甲烷、1-溴-3-甲基-2-丁烯缩合成花椒毒素与欧前胡素，总收率分别为35%与37%，其结构经IR、1HNMR、13CNMR与MS表征。这为合成天然产物花椒毒醇、花椒毒素与欧前胡素提供了一种较为简便的方法，同时为此类化合物的合成与应用提供了参考。
关键词：花椒毒醇；花椒毒素；欧前胡素；Pechmann缩合；Baeyer-Villiger氧化；合成
中图分类号：O626 文献标识码：A 文章编号：0258-3283（2020）
Synthesis of Xanthotoxol, Xanthotoxin and Imperatorin WANG Yue-qiu, LIANG Da-wei*, LI Xiao-mei, YE Qun-li (School of Pharmacy and Medical Laboratory Science, Ya’an Polytechnic College, Ya’an 625000, China), Huaxue Shiji, 2020, 42(6)
Abstract: Xanthotoxol, xanthotoxin and imperatorin are natural coumarins which possess promising potential biological activities. The synthesis of xanthotoxol has been achieved in 4 steps with a 42% yield from the commercially available 2,6-dihydroxyacetophenone and bromoacetaldehyde diethyl acetal via condensation and cyclization reactions. The pyran-2-one moiety and substitution of the hydroxy group were constructed by a sulfuric acid-catalyzed Pechmann condensation with malic acid and a Baeyer-Villiger oxidation. Then, the condensation of xanthotoxol with iodomethane and 1-bromo-3-methyl-2-buten produced xanthotoxin and imperatorin, respectively. The total yield was 35% and 37%. The structures were confirmed by IR, 1HNMR, 13CNMR and MS. The concise synthetic strategy allows rapid access to xanthotoxol, xanthotoxin and imperatorin, and offers a reference for the synthesis and application of related compounds.
Key words: xanthotoxol; xanthotoxin; imperatorin; Pechmann condensation; Baeyer-Villiger oxidation; synthesis
引用本文：王悦秋，梁大伟，李小梅，等. 花椒毒醇、花椒毒素与欧前胡素的合成[J]. 化学试剂，2020, 42(6): 735-738.
福沙匹坦二甲葡胺的合成工艺改进研究
刘春晖1，马晓莉*1, 2
（1. 北方民族大学 化学与化学工程学院，宁夏 银川 750021；2. 北方民族大学化工技术基础国家民委重点实验室，宁夏 银川 750021）
摘要：报道了合成标题化合物的新工艺。以(2R, 3S)-2-((1R)-1-(3,5-双(三氟甲基)苯基)乙氧基)-3-(4-氟苯基)吗啉盐酸盐为起始物料，与5-氯甲基-2,4-二氢[1,2,4]三唑-3-酮反应得到5-[[(2R,3S)-2-[(1R)-1-[3,5-二(三氟甲基)苯基]乙氧基]-3-(4-氟苯基)-4-吗啉]甲基]-1,2-二氢-3H-1,2,4-三氮唑-3-酮，即阿瑞匹坦。将得到的阿瑞匹坦在碱性条件下与焦磷酸四苄酯反应得到二-O-苄基磷酸酯。然后于高压釜中采用钯碳氢化还原后与N-甲基-D-葡糖胺成盐，最终通过精制得到合格的标题化合物，收率为61.8%。标题化合物经1HNMR、13CNMR和HR-MS确认结构，本路线切实可行、条件温和、产品质量可控，具有一定的工业价值。
关键词：福沙匹坦二甲葡胺；阿瑞匹坦；合成；工艺；优化
中图分类号：TQ463 文献标识码：A 文章编号：0258-3283（2020）
Improved Synthesis of Fosapitant Dimeglumine LIU Chun-hui1, MA Xiao-li*1,2 (1.School of Chemistry and Chemical Engineering, North Minzu University, Yinchuan 750021, China; 2.Key Laboratory of Chemical Engineering and Technology, State Ethnic Affairs Commission, North Minzu University, Yinchuan 750021, China), Huaxue Shiji, 2020, 42(6)
Abstract: A new process for the synthetic of Fosapitant dimeglumine was reported. (2R, 3S)-2-((1R)-1-(3, 5-Bis(trifluoromethyl) phenyl)ethoxy)-3-(4-fluorophenyl)morpholine hydrochloride as the starting material, it was reacted with 5-chloromethyl-2, 4-dihydro[1,2,4]triazol-3-one to give 5-[[(2R, 3S)-2-[(1R)-1-[3, 5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl) -4-morpholine]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one. It was Aprepitant. Aprepitant was reacted with tetrabenzyl pyrophosphate under alkaline conditions to obtain di-O-benzyl phosphate. Phosphate was reduced by palladium hydrocarbonization in autoclaves, then reacted with N-methyl-D-glucosamine to form a salt. The final sample was refined to obtain a qualified title compound, and the yield was 61.8%. The titile compound was confirmed by 1HNMR, 13CNMR and HR-MS. This route is feasible, with mild conditions, controllable product quality and certain industrial value.
Key words: Fosapitant dimeglumine; Aprepitant; synthesis; technology; optimize
引用本文：刘春晖, 马晓莉. 福沙匹坦二甲葡胺的合成工艺改进[J]. 化学试剂, 2020, 42(6):739-743.
二癸基聚羟乙基硼酸铵的一锅煮合成工艺
彭晓含a，黄文静a，夏天b，陈达b，张珍明a, c，李树安*b, c
(江苏海洋大学 a. 化工学院，b. 药学院，c. 江苏省海洋资源开发研究院，江苏 连云港 222005)
摘要: 二癸基聚羟乙基硼酸铵具有广泛的应用前景，可作木材抑菌剂。以二癸胺、环氧乙烷、硼酸为原料，微量水为引发剂，对甲苯磺酸为催化剂，乙酸乙酯为溶剂，合成二癸基聚羟乙基硼酸铵。经对各步反应条件进行考察，最佳工艺条件为n（胺）∶n（硼酸）∶n（环氧乙烷）= 2.0∶1.0∶5.0，反应温度为78 ℃，反应时间为6 h，此反应条件下季铵盐含量为92.0%。产物用IR、MS对其结构进行了表征。采用一锅煮的方法，操作简单，有效的提高了季铵盐的含量。
关键词：木材抑菌剂；二癸基聚羟乙基硼酸铵；优化；合成工艺
中图分类号：S785/O626 文献标识码：A 文章编号：0258-3283（2020）
One-pot Synthesis Process of Didecyl Polyoxyethyl Ammonium Borate PENG Xiao-hana, HUANG Wen-jinga, XIA Tianb, CHEN Dab, ZHANG Zhen-minga, c, LI Shu-an*b, c (a. School of Chemical Engineering, b. School of Pharmacy, c. Jiangsu Institute of Marine Resources, Jiangsu Ocean University, Lianyungang 222005, China), Huaxue Shiji, 2020, 42(6)
Abstract: Didecyl polyoxyethyl ammonium borate has a wide range of applications and can be used as a wood bacteriostatic agent. The didecyl polyoxyethyl ammonium borate was synthesized with didecylamine, ethylene oxide and boric acid as raw materials, water as initiator, p-toluenesulfonic acid as catalyst and ethyl acetate as solvent. Through examining the reaction conditions at each step, the optimum reaction conditions were as follows: n (amine)∶n (boric acid)∶n (ethylene oxide) = 2.0∶1.0∶5.0, heating to 78 ℃, reaction time 6 h, the content of quaternary ammonium salt was 92.0%. The structure of the product was confirmed by IR and MS. The one-pot synthesis method is simple to operate and effectively increases the quaternary ammonium salt content.
Key words: wood biocides; didecyl polyoxyethyl ammonium borate; optimization; synthesis
引用本文：彭晓含, 黄文静, 夏天, 等. 二癸基聚羟乙基硼酸铵的一锅煮合成工艺[J]. 化学试剂, 2020, 42(6):744-747.
