Chemoselective Arylsulfenylation of 2-Aminoimidazol[1,2-a]pyridines by Phenyliodine(III)
合成盐酸普拉格雷的工艺改进
合成盐酸普拉格雷的工艺改进段妍琴;陈国华;李素义【摘要】以邻氟溴苄为起始原料制得的格式试剂与环丙基氰反应,再经溴代、缩合、乙酰化和成盐反应制得抗血栓药物盐酸普拉格雷,总收率18.0％,其结构经1H NMR,MS和IR确证.%Prasugrel hydrochloride in overall yield of 18.0% was synthesized by the reaction of cycloprop yl cyanide with Grignard reagentof 2-fiuorobenzyl bromide, then by a four-step reaction of brominetion, condensation, acetylation and salification. The structure was characterized by 1H NMR, MS and IR.【期刊名称】《合成化学》【年(卷),期】2012(020)001【总页数】3页(P125-127)【关键词】盐酸普拉格雷;抗血栓药;药物合成;工艺改进【作者】段妍琴;陈国华;李素义【作者单位】中国药科大学药物化学系,江苏南京210009;中国药科大学药物化学系,江苏南京210009;中国药科大学药物化学系,江苏南京210009【正文语种】中文【中图分类】O626;R914.5盐酸普拉格雷{2-乙酰氧基-5-(α-环丙羰基-2-氟苄基)-4,5,6,7-四氢噻吩并[3,2-c]吡啶盐酸盐(1)}是由美国礼来公司和日本第一制药三共株式会社共同开发的口服抗血栓药物，是一种前体药物，在体内经过代谢后形成活性分子，与血小板膜上的腺苷二磷酸P2Y12受体结合而发挥抗血小板聚集的活性。
2009年7月，经FDA批准在美国首次上市，商品名Efient，临床上用于治疗动脉粥样硬化和急性冠状动脉综合征。
1作为血小板膜上的腺苷二磷酸P2Y12受体拮抗剂，临床显示其抑制血小板聚集的作用较已上市的同类药物氯吡格雷更快、更强和更持久，因此其作为新一代高效抗血栓药物必将具有十分广阔的应用前景[1]。
定量核磁共振波谱法快速测定灭火剂材料中全氟辛烷磺酰基化合物
分析测试新成果 (33 ~ 38)定量核磁共振波谱法快速测定灭火剂材料中全氟辛烷磺酰基化合物李 杨1, 3 ，黄 卫1 ，王 畅1 ，李 洋2 ，花 磊1 ，田 颖3（1. 中国科学院大连化学物理研究所，辽宁 大连 116023；2. 吉林工商学院，吉林 长春 130507；3. 大连交通大学，辽宁 大连 116023）摘要：泡沫灭火剂中全氟辛烷磺酰基化合物（PFOS ）的使用受到严格管控. 针对灭火剂中PFOS 快速测定的需求，建立了基于19F 的定量核磁共振波谱（qNMR ）检测方法. 方法以全氟丁基磺酸钾为标准物质，通过计算全氟丁基磺酸钾的-CF 3在化学位移δ −78.94处19F 特征峰和PFOS 的-CF 2在化学位移δ −117.12处19F 特征峰的积分面积比值，进而实现PFOS 定量分析. 经测试，全氟丁基磺酸钾百分含量与定量峰面积线性相关系数为0.995 5，检出限为0.024%，定量限为0.080%. 8种灭火剂产品的定性测定结果与实际标注情况相吻合，其中4种泡沫灭火剂产品中PFOS 含量在0.106%~1.339%之间. 研究结果表明，方法受基质干扰小、检测速度快、灵敏度高，可为泡沫灭火剂中PFOS 的管控提供可靠的检测方法与数据支撑.关键词：全氟辛烷磺酰基化合物；泡沫灭火剂；定量核磁共振波谱法；全氟丁基磺酸钾中图分类号：O657. 61 文献标志码：B 文章编号：1006-3757（2024）01-0033-06DOI ：10.16495/j.1006-3757.2024.01.006Rapid Determination of Perfluoroalkyl Sulfonyl Compounds in Foam Extinguishing Agents by Nuclear Magnetic Resonance SpectroscopyLI Yang 1, 3， HUANG Wei 1， WANG Chang 1， LI Yang 2， HUA Lei 1， TIAN Ying3（1. Dalian Institute of Chemical Physics , Chinese Academy of Sciences , Dalian 116023, Liaoning China ；2. Jilin Business College , Changchun 130507, China ；3. Dalian Jiaotong University , Dalian 116023, Liaoning China ）Abstract ：The usage of perfluorooctane sulfonyl compounds (PFOS) in foam extinguishing agents is strictly regulated. A quantitative nuclear magnetic resonance spectroscopy (qNMR) detection method based on 19F was established for the rapid determination of PFOS in fire extinguishing agents. Using potassium perfluorobutylsulfonate as the standard substance, the quantitative analysis of PFOS could be realized by calculating the integral area ratio of the 19F characteristic peak of -CF 3 in potassium perfluorobutylsulfonate at chemical shift δ −78.94 and the 19F characteristic peak of -CF 2 in PFOS at chemical shift δ −117.12. The linear correlation coefficient between the percentage content of potassium收稿日期：2023−11−10； 修订日期：2024−01−04.基金项目：国家自然科学基金项目（22174142），大连化物所创新研究基金项目（DICP I202144），辽宁省中央引导地方科技发展资金（2023JH6/100100057） [Natural Science Foundation of China (22174142), Dalian Institute of Chemical Physics (DICP I202144), Central Guidance on Local Science and Technology Development Fund of Liaoning Province (2023JH6/100100057)]作者简介：李杨（1978−），女，高级工程师，从事催化、材料、食品等方面快速分析应用技术研究，E-mail ：**************.cn 通信作者：花磊（1984−），男，研究员，《分析测试技术与仪器》青年编委，从事快速检测的谱学关键技术研究、仪器研制和应用开发，E-mail ：************.cn ；田颖（1969−），女，教授，从事水处理技术与材料研究，E-mail ：greenhusk@.第 30 卷第 1 期分析测试技术与仪器Volume 30 Number 12024年1月ANALYSIS AND TESTING TECHNOLOGY AND INSTRUMENTS Jan. 2024perfluorobutylsulfonate and the quantitative peak area was 0.995 5, the limit of detection was 0.024%, and the limit of quantitative was 0.080%. The qualitative determination results of 8 foam extinguishing agent products were consistent with the actual labeling, and the content of PFOS in 4 foam extinguishing agent products was 0.106%~1.339%. The research results showed that the method has the advantages of low matrix interference, fast detection speed, and high sensitivity, which could provide a reliable detection method and data support for the regulation of PFOS in foam extinguishing agents.Key words：perfluorooctane sulfonyl compounds；foam extinguishing agent；quantitative nuclear magnetic resonance spectroscopy；potassium perfluorobutylsulfonate以全氟辛烷磺酰基化合物（全氟辛烷磺酸、全氟辛烷磺酸盐及其衍生物的总称，以下简称PFOS）为代表的氟碳表面活性剂作为水成膜泡沫灭火剂（AFFF）的关键原材料，能够有效降低水溶液的表面张力，在可燃液体表面形成可以抑制燃料蒸发的水膜，隔绝液体燃料的挥发，具有良好的灭火性能. 添加PFOS的AFFF是目前扑灭液体火灾最为有效和常用的灭火剂，被广泛使用[1]. 但是PFOS性质稳定、难以降解，具有环境持久性、生物蓄积性和高毒性，在生物链中长期累积会造成严重的环境污染和健康问题[2]. 2009年，PFOS被正式列入《关于持久性有机污染物的斯德哥尔摩公约》[3]，包括中国在内的全球160多个国家政府最终达成共识将限制使用PFOS系列化合物. 作为目前PFOS使用的最大领域，泡沫灭火剂的生产和使用受到持续广泛关注，因此建立一种准确、快速、简便的泡沫灭火剂中PFOS快速检测方法具有重要的现实意义.目前含氟化合物测试方法主要有氟离子选择电极法[4]、比色法[5]、离子色谱法[6]和高效液相色谱-串联质谱法[7]. 氟离子选择电极法不受色度干扰，但是存在溶液浑浊、电极响应慢、回收率低等问题. 比色法仪器简单，但是前处理繁琐导致检验周期太长，且重复性不好. 离子色谱法具有快速、灵敏、稳定性高、选择性好等突出优点，但是受样品基体效应影响较大、预处理条件要求高[8]. 高效液相色谱-串联质谱法是目前分析PFOS、全氟辛酸化合物（PFOA）等物质的首选方法，但是此方法样品前处理复杂、操作步骤繁琐、耗时长.定量核磁共振波谱（qNMR）法用于定量分析的基础是不同化学环境中的原子核共振吸收峰面积，只与它的原子数有关，而与它在分子中所处的化学环境无关，因此与传统的定值方法相比，qNMR具有极大的优势[9]. 比如，19F NMR吸收峰面积只与产生NMR信号的19F核数目有关，所以用作标准参考的峰强度，既可以属于未知化合物本身（分子内内标），也可以是加入另外一种物质的信号（分子间内标）. 在待测样品中加入已知量的内标样品，通过计算内标化合物特征峰面积与样品中某一特征峰面积的比值，即可得到目标组分的浓度.近年来，qNMR方法被广泛用于药物研制[10-13]、中药质控[14-16]、聚合物分析[17-18]与代谢组学[19-20]等领域中的含氟化合物的定量分析[21-23].本研究采用基于19F的qNMR表征手段，以全氟丁基磺酸钾作为标准物质，建立了泡沫灭火剂中PFOS精准、快速的分析方法，评估了方法对PFOS 测定的重复性、线性关系及定量分析性能，并对8种灭火剂产品中含有PFOS的情况进行了快速鉴定和定量分析.1 试验部分1.1 仪器与试剂Spinsolve台式核磁共振仪（德国magritek公司）；电子分析天平LE104E（梅特勒-托利多仪器（上海）有限公司）；全氟丁基磺酸钾（98%，上海迈瑞尔化学技术有限公司）；氘代水（99.9%，广州旭谱实验室设备有限公司）；不含PFOS的泡沫灭火剂样品和含PFOS的泡沫灭火剂样品均由泡沫灭火剂生产厂商提供，产地分别为洛阳、江苏、上海、宁波；所用试剂均为分析纯.1.2 试验参数用探头为5 mm 19F检测信号，弛豫延迟时间为46.76 s；脉冲宽度为12 µs；氟核磁共振频率为58.67 MHz；带宽为20 000 Hz；采集点数为65 536点；试验时间（AQ）为6 min，扫描次数64次，样品体积约1 mL，试验均在22 ℃室温下进行.1.3 试验方法1.3.1 样品处理称取质量约500 mg（精确至0.1 mg）的泡沫灭34分析测试技术与仪器第 30 卷火剂样品直接加入核磁管，再加入质量为4.3～20.2 mg（精确至0.1 mg）的高纯全氟丁基磺酸钾作标准物质，超声处理至核磁管内样品和标准物质完全溶解后备用.1.3.2 定量核磁共振测定计算方法选择待测样品的19F NMR谱图中化学位移δ−117.12处的峰（-CF2）为PFOS定量峰，计算其积分面积，选取标准物质全氟丁基磺酸钾的19F NMR谱图中化学位移δ −78.94处的三重峰（-CF3）为定量峰，计算其积分面积. 通过如下公式计算得到待测样品中待测样品中PFOS的含量：式中：W t —泡沫灭火剂样品中全氟辛烷磺酸化合物的百分含量，%；F s —样品-CF2的19F积分面积；F i —标准物质-CF3的19F积分面积；m s —样品质量，mg；mi —标准物质质量，mg；Ms—样品分子量（此处以全氟辛基磺酸钾计，即538.22）；M i —标准物质分子量（此处以全氟丁基磺酸钾计，即338.19）；W r—标准物质质量百分含量，%；N s —样品分子中产生相应吸收峰的19F核数目；N i —标准物质分子中产生相应吸收峰的19F核数目.2 结果与讨论2.1 标准物质选择作为分子量最小的全氟烷基磺酸钾，全氟丁基磺酸钾价格低廉、易于获取，更重要的是全氟丁基磺酸钾的NMR特征峰与待测PFOS组分的NMR 特征峰，以及泡沫灭火剂样品基质组分的NMR谱峰有很好的分离，如图1所示. 因此，选择全氟丁基磺酸钾作为标准物质定量泡沫灭火剂中的PFOS. 2.2 定量峰选择对比不含PFOS泡沫灭火剂样品和含PFOS泡沫灭火剂样品的NMR谱图，如图1（a）（b）所示，可知：PFOS组分在化学位移δ −117.12和−79.87处的两个NMR谱峰分别对应于PFOS的-CF2和-CF3的特征峰，然而不含PFOS的泡沫灭火剂样品在化学位移δ −79.76处有一个较宽的背景干扰峰，与PFOS组分的化学位移δ −79.87谱峰相互重叠，产生干扰，因此选择PFOS的-CF2在化学位移δ −117.12处的峰为PFOS的定量峰，计算其积分面积. 同时，全氟丁基磺酸钾的19F NMR谱图中化学位移δ−78.94处-CF3的三重峰信号强度最高[图1（c）]，且不受基质干扰，因此可选其作为标准物质全氟丁基磺酸钾的定量峰，计算其积分面积.2.3 NMR扫描次数影响在501.2 mg含PFOS的泡沫灭火剂样品中加入15.6 mg高纯全氟丁基磺酸钾标准物质，超声处理至核磁管内样品和标准物质完全溶解后用NMR 测试，NMR扫描次数分别设置为8、16、32、64、128、256次，得到样品的19F NMR谱图中化学位移δ −117.12处的特征峰相对定量峰面积结果如表1所列. 从测试结果可见，核磁扫描次数在32次以上信号强度趋于稳定，在兼顾信噪比情况下，本试验选择扫描次数64次为宜.2.4 方法验证2.4.1 样品中PFOS组分测定重复性试验分别称取(500±0.5) mg含PFOS的泡沫灭火剂样品，组成12组平行样，进行重复性试验，结果如图2所示. 连续进行12次重复性试验，测试发现样品的19F NMR谱图中化学位移δ −117.12处的特征−79.76−79.87−78.94−112.69−119.84−124.−117.12(a)(b)(c)−80−90−100−110−120−130−80−90−100−110−120−130−80−90−100δ/ppmδ/ppmδ/ppm−110−120−130图1 定量核磁测定结果对比谱图（a）不含PFOS泡沫灭火剂样品，（b）含PFOS泡沫灭火剂样品，（c）全氟丁基磺酸钾标准品Fig. 1 Comparison spectra of quantitative NMR results(a) sample of foam extinguishing agent without PFOS,(b) sample of foam extinguishing agent containing PFOS,(c) potassium perfluorobutylsulfonate第 1 期李杨，等：定量核磁共振波谱法快速测定灭火剂材料中全氟辛烷磺酰基化合物35峰相对定量峰面积平均值为3.01，相对标准偏差为3.75%.2.4.2 线性关系与定量分析性能称取标准物质全氟丁基磺酸钾1.5、3.1、6.1、12.1、20.1、37.2 mg 并分别溶解于0.5 mL 氘代水中，测试得到的标准物质全氟丁基磺酸钾对应定量峰面积和其质量浓度的标准曲线. 结果如图3所示，线性相关系数为0.995 5，可以作为定量测试泡沫灭火剂样品中PFOS 的定量依据. 本方法用所拥有的最低含PFOS 泡沫灭火剂样品进一步稀释后，按照3倍噪声计算得到样品检出限为0.024%，10倍噪声计算得到样品定量限为0.080%.2.4.3 实际样品分析采用本方法对共计8种实际泡沫灭火剂产品进行测试，图4为加入全氟丁基磺酸钾的含PFOS 泡沫灭火剂样品（1#）的NMR 谱图. 结果显示，对于样品是否含有PFOS ，采用本方法进行定性测定的结果与生产厂家标注的实际情况相吻合. 同时对4种含有PFOS 的样品进行了定量，结果如表2所列.4相对定量峰面积3212468重复次数1012图2 检测泡沫灭火剂样品中PFOS 的重复性考察Fig. 2 Repeatability test for detection of PFOS in foamextinguishing agent samples1.61.20.80.4123W r456H 0H 0=0.279 W rR 2=0.995 5图3 全氟丁基磺酸钾为标准物质测定PFOS 的标准曲线（H 0表示相对定量峰面积，W r 表示全氟丁基磺酸钾的质量分数）Fig. 3 Standard curve for determination of PFOS using potassium perfluorobutylsulfonate as the standardsubstance−80−90−100−110−120−130δ/ppm−78.94−112.69−117.12−119.84−124.00图4 加入全氟丁基磺酸钾的含PFOS 泡沫灭火剂样品（1#）的NMR 谱图Fig. 4 NMR spectrum of foam extinguishing agent product (1#) containing PFOS added with potassiumperfluorobutylsulfonate表 1 扫描次数对相对定量峰面积的影响Table 1 Effect of scanning times on relative quantitativepeak areas扫描次数相对定量峰面积信噪比8 2.45 5.2516 2.49 5.2232 2.84764 2.8412128 2.84122562.8412表 2 含有PFOS 泡沫灭火剂产品的实测定量结果Table 2 Quantitative measurement results of foam extinguishing agent products containing PFOS 样品编号实测PFOS 的质量分数/%1#0.1883# 1.3396#0.1068#0.11036分析测试技术与仪器第 30 卷3 结 论qNMR 法不依赖于被测物的高纯度标准品、不破坏样品，仅需样品组分有一个或一组互不干扰的特征NMR 峰，依据信号峰的面积正比于产生该共振峰的质子数，即可进行定量分析. 本文基于定量qNMR 技术，建立了以全氟丁基磺酸钾作为标准物质快速测量灭火剂中PFOS 的方法. 经系统测试，本方法重复性好、灵敏度高、准确可靠，对快速科学地掌握我国消防行业PFOS 的使用情况，加强PFOS 管控工作，减少进出口贸易摩擦具有重要的意义.参考文献：亓磊, 焦金庆, 熊靖, 等. 用于液体火灾的环保泡沫灭火剂研究现状[J ]. 材料导报，2022，36（20）：29-35.[QI Lei, JIAO Jinqing, XIONG Jing, et al. 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[SHANG Xu-dong, WANG Chang, YU Jingyuan, et al. Colorimet-ric detection of fluoride ion by oxidase mimics based oncericdioxidenanorods-polyvinylalcoholaerogel [J ]. Chinese Journal of Analytical Chemistry ，［ 5 ］2021，49 （12）：2023-2031.]肖苏熠, 孙长恩, 洪华, 等. 气相色谱法分析氟丙菊酯[J ]. 江苏科技信息，2016（13）：79-80. [XIAO Suyi, SUN Changen, HONG Hua, et al. Analysis on acrcnathrin by gas chromatogrphy [J ]. Jiangsu Sci-ence & Technology Information ，2016 （13）：79-80.]［ 6 ］郑丽利, 江敏, 吴昊, 等. 高效液相色谱-串联质谱法测定水中全氟辛烷磺酸含量[J ]. 上海海洋大学学报，2022，31（1）：181-190. [ZHENG Lili, JIANG Min,WU Hao, et al. Determination of perfluorooctane sulf-onic acid in water by high performance liquid chroma-tography-tandem mass spectrometry [J ]. Journal of Shanghai Ocean University ，2022，31 （1）：181-190.]［ 7 ］车明秀, 泮秋立, 胡明燕, 等. 食品中氟检测分析的研究进展[J ]. 中国食品卫生杂志，2023，35（1）：137-141. [CHE Mingxiu, PAN Qiuli, HU Mingyan, et al.Research progress on the fluoride detection and ana-lysis in different food samples [J ]. 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Forensic Science and Technology ，2023（3）：262-267.]［ 12 ］郑妩媚, 李晓蒙, 王姣姣. 核磁共振法定性和定量分析磷酸奥司他韦胶囊[J ]. 化学研究与应用，2022，34（11）：2735-2739. [ZHENG Wumei, LI Xiaomeng,WANG Jiaojiao. Qualitative and quantitative analysis of oseltamivir phosphate capsules by nuclear magnetic resonance [J ]. Chemical Research and Application ，［ 13 ］第 1 期李杨，等：定量核磁共振波谱法快速测定灭火剂材料中全氟辛烷磺酰基化合物372022，34 （11）：2735-2739.]陈燕燕, 李晓男, 王跃飞, 等. 解卷积定量核磁共振法测定黄芪注射液中8种初生代谢成分[J]. 分析化学，2015，43（8）：1210-1217. [CHEN Yanyan, LI Xiao-nan, WANG Yuefei, et al. Quantificative determina-tion of 8 primary metabolites in Huangqi injectionby 1H NMR with deconvolution[J]. Chinese Journalof Analytical Chemistry，2015，43 （8）：1210-1217.]［ 14 ］Yang M H, Wang J S, Kong L Y. Quantitative analys-is of four major diterpenoids in Andrographis panicu-lata by 1H NMR and its application for quality controlof commercial preparations[J]. Journal of Pharma-ceutical and Biomedical Analysis，2012，70 ：87-93.［ 15 ］Zhao F, Li W Z, Pan J Y, et al. A novel critical con-trol point and chemical marker identification methodfor the multi-step process control of herbal medicinesvia NMR spectroscopy and chemometrics[J]. RSCAdvances，2020，10 （40）：23801-23812.［ 16 ］叶怀英, 孟庆文, 余国军, 等. 核磁共振技术在含氟聚合物定量分析中的应用[J]. 化工生产与技术，2022，29（5）：29-32, I0004. [YE Huaiying, MENG Qingwen,YU Guojun, et al. Application of nuclear magnetic res-onance technology in quantitative analysis of fluoro-polymers[J]. Chemical Production and Technology，2022，29 （5）：29-32, I0004.]［ 17 ］Mazarin M, Viel S, Allard-Breton B, et al. Use ofpulsed gradient spin-echo NMR as a tool in MALDImethod development for polymer molecular weightdetermination[J]. Analytical Chemistry，2006，78 （8）：2758-2764.［ 18 ］王峥, 黄慧英, 徐庆妍, 等. 对苯二甲酸二钠内标在定［ 19 ］量核磁共振代谢组学中的应用[J]. 厦门大学学报(自然科学版)，2022，61（1）：105-111. [WANGZheng, HUANG Huiying, XU Qingyan, et al. Applica-tion of disodium terephthalate as an internal standardin the quantitative NMR-based metabolomics[J].Journal of Xiamen University (Natural Science)，2022，61 （1）：105-111.]吴香玉, 李宁, 唐惠儒. 绿豆(Vigna Radiata)代谢物组成的核磁共振定量分析[J].波谱学杂志，2014，31（4）：548-563. [WU Xiangyu, LI Ning, TANGHuiru. Quantitative analysis of metabolites in mung-bean (Vigna Radiata) extracts using NMRtechniques[J]. Chinese Journal of Magnetic Reson-ance，2014，31 （4）：548-563.]［ 20 ］He W Y, Du F P, Wu Y, et al. Quantitative 19F NMRmethod validation and application to the quantitativeanalysis of a fluoro-polyphosphates mixture[J]. Journ-al of Fluorine Chemistry，2006，127 （6）：809-815.［ 21 ］于小波, 罗楚平, 卢爱民. 19F核磁共振定量波谱测定环吡氟草酮含量[J]. 农药，2018，57（9）：645-646,674. [YU Xiaobo, LUO Chuping, LU Aimin. Determ-ination of huanbifucaotong by 19F quantitative nuclearmagnetic resonance[J]. Agrochemicals，2018，57 （9）：645-646, 674.]［ 22 ］华俊杰, 朱海菲, 李育. 19F核磁共振定量法测定含氟漱口液中氟化钠的含量[J]. 药学实践杂志，2019，37（6）：518-520. 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L-脯氨酸催化的醛的不对称α-硫代反应
L-脯氨酸催化的醛的不对称α-硫代反应袁飞鹏;李长思;俞健钧;戴振亚;尤启冬;王德峰【摘要】目的:对L-脯氨酸催化醛的不对称α-硫代反应进行研究.方法:以L-脯氨酸为催化剂,将正丙醛和正丁醛分别与7种硫代试剂在-40 ℃下反应6小时.结果:合成了14个α-硫代醛类化合物,结构经1H-NMR确证.结论:L-脯氨酸可催化醛的α-硫代反应,且产率较高,具有一定实用价值.【期刊名称】《药学进展》【年(卷),期】2010(034)012【总页数】5页(P554-558)【关键词】L-脯氨酸;醛的α-硫代;不对称催化【作者】袁飞鹏;李长思;俞健钧;戴振亚;尤启冬;王德峰【作者单位】中国药科大学药物化学教研室,江苏,南京,210009;中国药科大学药物化学教研室,江苏,南京,210009;南通华峰化工有限责任公司,江苏,南通,226531;江苏德峰医药化工有限公司,江苏,南通,226531;江苏含多个杂原子杂环工程中心,江苏,南京,210009;中国药科大学药物化学教研室,江苏,南京,210009;中国药科大学药物化学教研室,江苏,南京,210009;南通华峰化工有限责任公司,江苏,南通,226531;江苏德峰医药化工有限公司,江苏,南通,226531;江苏含多个杂原子杂环工程中心,江苏,南京,210009【正文语种】中文【中图分类】R914.5α-硫代羰基化合物为有机合成反应中重要的中间体,可被氧化为磺酸类或亚砜类化合物,若采用手性氧化的方法则可得到具有手性的亚砜类化合物,后者可作为重要的手性配体用于不对称催化反应中;此外,α-硫代羰基化合物还可用于合成一些杂环类化合物[1-2]。
α-硫代羰基化合物的常见制备方法包括烯醇(盐)的硫代反应[3-7]和α-卤代羰基化合物的取代反应[8]。
采用上述方法前,需将羰基化合物修饰为烯醇盐或烯胺[9-10],故而对醇钠的消耗量较大。
国内外对于未经修饰、直接催化的醛酮的α-硫代反应鲜有报道,目前只有Wang等[11]曾报道使用仲胺催化的未经修饰的醛的α-硫代反应;此外,手性α-硫代羰基化合物的合成均需使用手性辅剂[12-16],其价格昂贵且不易回收。
二硫缩烯酮
School of Chemical Sciences, Mahatma Gandhi University, Priyadarshini Hills P. O., Kottayam 686 560, India Fax +91(481)2731009; E-mail: asokancv@ Received 2 April 2005; revised 4 July 2005
二硫缩烯酮 convenientpreparation 5-aroyl-2-oxo-1,2-dihydro-2-pyridinecarbonitriles preparation 2-aroyl-3,3-bis(alkylsulfanyl)acrylaldehydesengoor anabha,chittoorthekkathil asokan*school chemicalsciences, mahatma gandhi university, priyadarshini hills kottayam686 560, india fax +91(481)2731009; e-mail: asokancv @ received april2005; revised july2005 erally, a-formyl derivatives ketenedithioacetals obtainedindirectly from correspondingbis(methylsul- fanyl)ethylene carboxylates via process.rudorf et al. reported fromaroylacetaldehydes treatingthem carbondisulfide abstract: aroylketenedithioacetals vilsmei-er–haack reagent, prepared from pocl undermild con- ditionsgave 2-aroyl-3,3-bis(alkylsulfanyl)acrylaldehydes excellentyields. cyclization 2-[2-aroyl-3,3-bis(methylsulfanyl)-2-propylidene]malononitriles derivedfrom concentratedhydrochloric acid tertiarybutanol afforded 2-pyridone derivatives base,followed alkylation.most havekey words: ketene dithioacetals, knoevenagel condensations, cy- already been reporte
气相色谱法测定聚碳酸酯中的二氯甲烷
化学分析计量CHEMICAL ANALYSIS AND METERAGE第27卷，第5期2018年9月V ol. 27，No. 5Sept. 2018102doi ：10.3969／j.issn.1008–6145.2018.05.024气相色谱法测定聚碳酸酯中的二氯甲烷毕静利，孙彩虹，张艳君，张超（鲁西化工集团股份有限公司，山东聊城 252211）摘要 建立蒸馏提取–气相色谱法快速测定聚碳酸酯中二氯甲烷含量的方法。
以三氯甲烷作溶剂溶解聚碳酸酯，配制成含8%～10%聚碳酸酯的三氯甲烷溶液，在蒸馏温度为90℃，冷凝介质的温度为–15℃的条件下，通过蒸馏法将溶液中的三氯甲烷蒸出，用气相色谱法测定二氯甲烷的含量。
二氯甲烷的含量在1～80 mg ／kg 范围内与色谱峰面积呈良好的线性关系，线性相关系数为0.999 3，检出限为1.7 mg ／kg 。
二氯甲烷测定结果的相对标准偏差为1.64%（n =6），加标回收率为95.7%～100.3%。
该方法准确、可靠，可用于聚碳酸酯中二氯甲烷含量的快速检测。
关键词 气相色谱法；聚碳酸酯；二氯甲烷中图分类号：O657.7 文献标识码：A 文章编号：1008–6145(2018)05–0102–03Determining dichloromethane in polycarbonate by gas chromatographyBI Jingli ， SUN Caihong ， ZHANG Yanjun, ZHANG Chao(Luxi Chemical Industry Group Co.， Ltd.， Liaocheng 252211， China)Abstract The method for determination of dichloromethane in polycarbonate by gas chromatography was established. With chloroform as solvent ，polycarbonate was dissolved to 8%–10% of polycarbonate chloroform solution ，set the distillation temperature was 90℃，the cooling medium temperature was –15℃，chloroform was steamed out from the solution by distillation ，the content of dichloromethane was determined by gas chromatography. The content of dichloromethane had good linear relationship with the chromatographic peak area in the range of 1–80 mg ／kg, the linear correlation coefficient was 0.999 3, the detection limit was 1.7 mg ／kg. The relative standard deviation of determination results was 1.64%(n =6)，and the recovery rates were 95.7%–100.3%. The method is accurate ，reliable ，which is suitable for rapid determination of dichloromethane in polycarbonate.Keywords gas chromatography; polycarbonate; dichloromethane聚碳酸酯（PC ）是一种综合性能优良的热塑性工程塑料，具有优异的抗冲击性，尺寸稳定性，电绝缘性，自熄性，透光性等，是五大工程塑料中透光性最好的塑料。
化学化工术语英汉对照词典
English Chinese Bulk Drug原料药Sterile Bulk无菌原料药Large Volume Parenteral Solution大容量注射剂Small Volume Parenteral Solution小容量注射剂Powder for Injection粉针剂Lyophilized Powder for Injection冻干粉针剂Tablets片剂Capsules胶囊剂Soft Capsules软胶囊剂Granules颗粒剂Dry Suspension干悬浮剂Pills丸剂Pills Drops滴丸剂Powders散剂Oral Solutions口服溶液剂Oral Suspension口服悬浮剂Oral Emulsion口服乳剂Mixture合剂Syrup糖浆剂Medicinal Wine酒剂Medicinal Teas茶剂Tincture酊剂Membrane膜剂Eye Drops滴眼剂Ear Drops滴耳剂Nasal Drops滴鼻剂Lotion洗剂Enemas灌肠剂Suppositories栓剂Liniment搽剂Aromatic Solution露剂Emulsion乳剂Solution溶液剂Aerosol气雾剂Spray喷雾剂Inhalation吸入剂Ointment软膏剂Plastic涂膜剂Cream乳膏剂Paste糊剂Gels凝胶剂Colloid胶体Subdermal植入剂Plaster硬膏剂Cataplasmata巴布膏剂Transdermal透皮贴剂Adhesive Plaster橡皮膏剂Concentracted Decoctions煎膏剂Fluid Extract流浸膏剂Liquid Extract流浸膏剂Extract浸膏剂Elixir酏剂Spirit醑剂Eye Ointment眼膏剂Pastille锭剂Prepared Slices of Chinese Crude Drugs中药饮片Radiopharmaceutical放射性药剂Biological Products生物制品Blood Products血液制品Extrinsic Diagnostic Tests体外诊断试剂Medical Oxygen医用氧Contrast Media造影剂Penicillins青霉素类Cephalosprins头孢菌素类Hormones激素类Antineoplastic Drugs抗肿瘤药Prophylactic Drugs避孕药claim权利要求alternatively可选择地those skilled in the art本领域技术人员present invention本发明background art背景技术Technical Field技术领域particularly特别地more particularly更特别地preferably优选地more preferably更优选地wherein其中accordingly因此and the like等等applicant申请人application申请assign转让assignee受让人assigner转让人CIP部分继续（申请）continuation in part部分继续（申请）component组分composition组合物consist of由……组成description说明书disclose披露/公开drawing附图e.g.例如such as如for example例如i.e.即et. al.等人formulation制剂optionally任选地prior art现有技术in particular特别地subject主体/受试者said所述thereof其thereafter其后therefore因此thereby由此associated缔合的angiogenesis血管新生aminoalkyl氨烷基associate缔合物analgesic止痛的/止痛剂alkylamino烷氨基alkylthio烷硫基band（电泳）条带complimentary互补的fused稠合的homologic同源的homogenous同质的in situ就地/在原处indicator指示剂labelled标记的nucleotide核苷酸nucleoside核苷abridgment节略abstract摘要infringement侵权affidavit誓书amendment修改voluntary amendment主动修改annual fee年费official fee官费applicant for patent专利申请人application date申请日期application documents申请文件application fee申请费application number申请号arbitration仲裁assignment转让inventor发明人commissioner专利局长compulsory license强制许可period期限priority优先权copyright版权country code国家代码data of application申请日期data of grant授权日期defendant被告plaintiff原告deferred examination延迟审查dependent claim从属权利independent claim独立权利division分案examiner审查员novelty新颖性inventive step创造性first to file principle先申请原则first to invention principle先发明原则gazette公报grace period宽限期intellectual property知识产权invalidation无效national treatment国民待遇non-obviousness非显而易见性office action专利局审查决定书parent application原申请/母案patent agency专利代理机构patent agent专利代理人patent attorney专利代理人patent number专利号patent right专利权patent rules专利实施细则petition请求书reexamination复审refusal驳回remedy补救request请求书revocation撤销specification说明书substantive examination实质性审查succession继承trade mark商标unity单一性utility model实用新型withdrawal撤回taxonomic category分类阶元domain域kingdom界phylum门class纲order目family科genus属species种method方法acetate乙酸盐/乙酸酯dialysate透析液anticoagulant抗凝的/抗凝剂bicarbonate碳酸氢盐/二碳酸酯sodium钠buffer缓冲液metabolic代谢的metabolite代谢物metabolism代谢concentration浓度precipitation沉淀calcium钙magnesium镁commercially available商购的/市售获得的especially尤其inhibition抑制hydrogen氢helium氦lithium锂boron硼carbon碳nitrogen氮oxygen氧fluorine氟neon氖aluminium铝silicon硅phosphorus磷sulfur硫chlorine氯argon氩potassium钾iron铁nickel镍copper铜zinc锌arsenic砷stannum锡bromine溴silver银gold金manganese锰heparin肝素pericarditis心包炎coagulopathy凝血障碍thrombocytopenia血小板减少症cerebral hemorrhage脑溢血saline盐水hypocalcemia低血钙症citrate枸橼酸盐/枸橼酸酯hypotension低血压hypertension高血压cardiovascular心血管spasm痉挛nausea恶心chloride氯化bromide溴化fluoride氟化iodide碘化oxide氧化hydroxide氢氧化hydrochloric acid盐酸lactic acid乳酸malic acid苹果酸in accordance with依照/按照/根据embodiment实施方案example实例/实施例hereinafter以下include包括comprise包含contain含有herein此处illustrative purpose说明性目的purified water纯净水Furthermore此外however然而according to根据induce引起lead to导致cause造成table表figure图scheme图表prepare制备preparation制备/制剂manufacture制备use用途mixture混合物relate to涉及safety range安全范围placebo安慰剂chelating agent螯合剂target cell靶细胞albumin白蛋白microballoon微球percentage百分比semisynthetic半合成antibiotic抗生素haptene半抗原half life period半衰期half life time半衰期coated tablet包衣片saturated饱和的unsaturated不饱和的passive immunity被动免疫passive transport被动转运disintegration崩解度disintegrant崩解剂essential必需allergy变态反应/过敏surface activity表面活性surfactant表面活性剂surface tension表面张力gamma rayγ射线complement补体adverse reaction不良反应side effect副作用antigen抗原antibody抗体complex复合物enterohepatic 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cycle三羧酸循环bactericidal杀菌pesticidal杀虫phytocidal除草的fungicidal杀真菌的viricidal杀病毒的neurotoxin神经毒素adrenergic肾上腺素能osmotic pressure渗透压phenylpropionic acid苯丙酸coumarin香豆素lignan木脂体/木质素anthraquinone蒽醌flavonoid黄酮terpenoid萜类alkaloid生物碱steroid甾体bioavailability生物利用度chiral手性first pass effect首过效应antagonist拮抗剂agonist激动剂double-blind双盲hydrolysis水解gluconeogenesis糖异生isotope同位素mutation突变phagocytosis吞噬作用exotoxin外毒素aqua regia王水microsome微粒体microsomal微粒体potency效价synergy协同作用efficacy有效性safety安全性controlability可控性selectivity选择性chemoselectivity化学选择性regioselectivity区域选择性stereoselectivity立体选择性intramolecular分子内intermolecular分子间intravascular血管内extravascular血管外administration施用/给药plasma血浆serum血清whole blood全血vascular血管blood brain barrier血脑屏障coagulation凝聚equivalence等效性absorption吸收distribution分布excretion排泄elimination消除isomerase异构酶nutrient营养素threshold value阈值carrier载体saponin皂苷linear correlation线性相关carcinogen致癌物teratogen致畸物mutagen致突变物preparation制剂combination组合物intermediate中间体adjuvant佐剂medicinal药物/药品/药用pharmaceutical药学/药物/制药synthetic合成split into分成starting material起始原料synthesis合成（法）lead先导lead铅mercury汞/水银isolation分离extraction提取extract提取物extract萃取物extract浸膏purification纯化elucidation解析identification鉴定precursor前体insulin胰岛素heart心脏liver肝脏spleen脾脏lung肺脏kidney肾脏brain大脑cerebellum小脑brain stem脑干eyebrow眼眉eye眼睛ear耳朵nose鼻子mouth嘴tongue舌头neck脖子/颈部shoulder肩arm手臂the upper arm上臂forearm前臂trunk躯干pharynx咽部throat喉trachea气管stomach胃pancreas胰腺gallbladder胆intextines肠anus肛门chest胸abdomen腹back背leg腿knee膝盖ankle踝finger手指toe脚趾muscle肌肉tissue组织organ器官embryo胚胎sperm精子egg卵细胞/蛋zygote受精卵/合子chromosome染色体nail指甲wrinkle皱纹lip嘴唇heel脚后跟/踵wrist腕fist拳头palm手掌cholesterol胆固醇amino acid氨基酸gelatine明胶interferon干扰素dextran葡聚糖/右旋糖酐lactam内酰胺lactase乳糖酶lactone内酯carboxylic 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combination of与……组合by means of借助于mucic acid粘酸fumaric acid富马酸maleic acid马来酸succinic acid琥珀酸sorbic acid山梨酸ascorbic acid抗坏血酸/维生素C citric acid枸橼酸/柠檬酸homogeneous同源的heterogeneous异源的registration注册organometallic有机金属toluene甲苯xylene二甲苯water水methanol甲醇ethanol乙醇propanol丙醇butanol丁醇cinnamyl肉桂基lauryl月桂基stearyl硬脂酰基oleoyl油酰基linoleoyl亚油酰基acetone丙酮dichloromethane二氯甲烷chloroform氯仿tetrahydrofuran四氢呋喃dioxin二氧六环/二恶英ethyl acetate乙酸乙酯triethylamine三乙胺diisopropylethylamine二异丙基乙胺ammonia solution氨溶液/氨水impurity杂质penetration渗透structure-activity relationship构效关系partition coefficient分配系数configuration构型conformation构象tartaric acid酒石酸asymmetric不对称solubility溶解度sequence序列in vivo体内in vitro体外epoxidation环氧化predominant主要dehydrase脱水酶dehydrogenase脱氢酶decarboxylase脱羧酶entity实体anti-infectives抗感染onset着手stability稳定性foetal胎儿rodent啮齿类tannin鞣质/单宁vacuum真空gallic acid没食子酸precipitate沉淀物sediment沉淀distillation蒸馏distill蒸馏salicylic acid水杨酸flask烧瓶beaker烧杯condenser冷凝器cation阳离子anion阴离子decolorize脱色degradation降解antithrombin抗凝血酶thrombin凝血酶sterile无菌的/灭菌的solubilizer助溶剂dispersing agent分散剂antifoaming agent消泡剂clinical临床trial试验protocol方案official compendium法定药典labeled amount标示量batch number批号calibration校正funnel漏斗test tube试管evaporating dish蒸发皿Erlenmeyer flask锥形瓶measuring cylinder量筒washing bottle洗瓶casserole勺皿separalory funnel分液漏斗water bath水浴oil bath油浴ice bath冰浴steam bath蒸气浴stirring bar搅拌子magnetic stirrer磁力搅拌器analytical balance分析天平pipette移液管pipet吸量管rubber suction bulb洗耳球glass rod玻璃棒stopcock玻璃活塞pyknowmeter flask容量瓶dropper滴管medicine spoon药匙volumetric flask容量瓶morta研钵/乳钵siderocradle铁架台burette滴定管rectocondensor直型冷凝器thermometer温度计qualitative定性quantitative定量accuracy准确度precision精密度deviation偏差ionization离子化dissociation解离electrode电极cathrode负极anode正极chromophore生色团auxochrome助色团absorbance吸光度fluorescence荧光internal conversion内转换external conversion外转换ultraviolet紫外visible可见infrared红外spectroscopy光谱学nuclear magnetic resonance核磁共振chemical shift化学位移singlet单峰doublet双峰triplet三重峰quartet四重峰quintet五重峰sextet六重峰coupling偶合geminal coupling偕偶vicinal coupling邻偶mass spectrum质谱interface接口mass range质量范围resolution分辨率sensitivity灵敏度molecular ion分子离子quasi-molecular ion准分子离子fragment ion碎片离子isotopic ion同位素离子metastable ion亚稳离子metastable peak亚稳峰homolytic cleavage均裂heterolytic cleavage异裂rearrangement重排molecular weight分子量stationary phase固定相chemically bonded phase化学键合相gradient梯度elution洗脱detector检测器mobile phase流动相fraction组分/部分eluent洗脱液isocratic等度centrifugal离心centripetal向心stepwise分步activation活化degassing脱气overloading过载acetaldehyde乙醛acetic anhydride乙酸酐achiral非手性retention保留abundance丰度digestion消化myopia近视hyperopia远视astimatism散光nyctalopia夜盲cholinergic胆碱能autocrine自分泌paracrine旁分泌stress应激feedback反馈abscissa横坐标analysis of data数据分析analysis of variance方差分析absolute number绝对数absolute value绝对值accident error偶然误差average平均degree of confidence置信度degree of freedom自由度degree of variation变异度cartogram统计图census普查chi-square test卡方检验correlation coefficient相关系数regression coefficient回归系数confident interval置信区间confident level置信水平confident limit置信限coordinate坐标correlation相关histogram柱状图/直方图critical value临界值mesokurtosis正态峰morbidity发病率/患病率mortality死亡率natality出生率normal curve正态曲线normal deviate正态离差normal distribution正态分布normal population正态总体one-sided test单侧检验one-tailed test单尾检验ordinate纵坐标mean均值parameter参数median中位数pie diagram饼形图regression回归probability概率proportion比率ratio比例sample样本sample样品random随机scaller diagram散点图significance显著性skewness偏态slope斜率standard deviation标准差standard error标准误standard normal distribution标准正态分布statistic统计量statistics统计学variable变量constant恒量two-sided test双侧检验two-tailed test双尾检验acrylic acid丙烯酸resin树脂plastic塑料rubber橡胶ceramic陶瓷adhersion粘附力adhersives粘合剂aggregation聚集amorphous无定形anhydrous无水antiadherent抗粘剂antioxidant抗氧化剂antiseptic防腐剂apparent表观aprotinin抑肽酶ascabin苯甲酸/苯甲酸酯benzoic acid苯甲酸bound water结合水breakage脆碎度cabomer卡波姆/羧基乙烯共聚物ceramide神经酰胺chitin甲壳素/几丁质chitosan壳聚糖cohesion凝聚力compactibility成形性/可压实性compressibility压缩性controlled-release控释cosolvent共溶剂cytotoxicity细胞毒性diluent稀释剂sulfoxide亚砜sulfone砜deionized去离子elastic弹性film膜剂flocculation絮凝flowability流动性freon氟利昂gelatin明胶glidant助流剂granule颗粒hydrophile-lipophile balance亲水亲油平衡值implant植入intradermal皮内intramuscular肌内intravenous静脉isoelectric等电isoosmotic等渗liposome脂质体paraffin石蜡wax蜡oil油lubricant润滑剂microcrystalline微晶cellulose纤维素microsphere微球nanocapsule纳米囊nanoemulsion纳米乳nanoliposome纳米脂质体nanoparticle纳米粒pharmacopoeia药典viscosity粘度poloxamer泊洛沙姆pluronic普郎尼克polyacrylic聚丙烯酸polyethylene聚乙烯polyethylene glycol聚乙二醇polyvinylpyrrolidone聚乙烯吡咯烷酮polyvinylpyrrolidine聚乙烯吡咯烷porosity孔隙率preservative防腐剂pyrogen致热原racemization外消旋化rubbing研磨safflower红花Tween吐温Span司盘subcutaneous皮下sublingual舌下sugar糖supercritical超临界suppository栓剂sustained-release缓释talc滑石粉transfersome传递体vaseline凡士林wool fat羊毛脂。
聚2-甲基丙烯酰氧基乙基磷酰胆碱改性聚合物研究
第42卷第9期塑料工业2014年9月CH I NA PLASTIC S I N DU S TR Y聚2一甲基丙烯酰氧基乙基磷酰胆碱改性聚合物研究术顾花林，林杨，王国尧，唐秀兰，吴宇浩，彭娅”(西华大学材料科学与工程学院，四川成都610039)摘要：聚2一甲基丙烯酰氧基乙基磷酰胆碱(PMPC)是一种具有极强亲水性和生物相容性的聚合物。
通过PMPC 改性材料表面获得生物相容性较好的生物医用材料已成为研究重点之一。
综述了PMPC的合成方法以及PMPC 改性聚合物的主要接枝方法，并展望了磷酰胆碱类聚合物的发展以及应用前景。
关键词：磷酰胆碱；改性；生物相容性；聚2一甲基丙烯酰氧基乙基磷酰胆碱DOI：10．3969／j．issn．1005—5770．2014．09．003中图分类号：TB34 文献标识码：A 文章编号：1005—5770(2014)09—0011—04Research on Modified Polymer、)l，ith Poly(2。
(methacryloyloxy)ethyl phosphorylcholine) GU Hua。
lin，LIN Yang，WANG Gu o—ya o，TA NG Xiu。
lan，WU Yu。
ha o，P ENG Ya(School of Ma t er ia l Sc ie nc e＆T ec hn ol og y，X ih ua Univ ersity，Chen gdu610039，Chi na)Abstract：Poly(2。
(methacryloyloxy)ethyl phosphorylcholine)(PMPC)was a highly hydrophilic and bio comp atib le poly mer．It w a s o n e of t he i mpo rta nt re se arc he s that the b iom edi cal materials with better biocompatibility cou ld be obt ai ned by surfa ce—grafting with PMPC polymers．This rev ie w focused o n th e synthesis of PMPC an d the grafting methods of co mp o s it e material by PM PC．At last，the development an d application p ro sp ec ts of the PMPC in future w e r e also prospected．Keywords：Phosphorylcholine；Modification；Biocompatibility；PMPC20世纪末，基于仿生学，Chapman等提出了通车H，r—I陌 i!H3c水CH，；过仿细胞外层膜结构即含有磷酰胆碱基团(PC)的，c H：|H：cg二l lKc、Q 聚合物对材料表面进行改性的观点¨qj。
表面活性剂月桂酰二乙醇胺的微波合成
表面活性剂月桂酰二乙醇胺的微波合成姚凯;袁霖;胡婷;袁先友;贾国凯;陶柳;刘佳【摘要】In this paper, lauroyl diethanolamine was synthesized by diethanolamine and methyl laurate catalyzed by KOH under microwave irradiation. Methyl laurate was prepared through the esterification of methanol with lauric acid which was purified from litsea cubeba kernel oil. The effect of factors on the yield were studied and the optimun reaction conditions were found. They are as follows: reaction temperature 170 ℃, reaction time 60 min, the amount of catalyst is one percent of the quality of methyl laurate, molar ratio of methyl laurate to diethanolamine is 1.6:1. Under this condition, The conversion rate of diethanolamine was 85.12%. The product was characterized by IR.% 探讨了以从山苍籽核仁油中提取出的月桂酸制得的月桂酸甲酯在微波辐射下，用 KOH 作为催化剂与二乙醇胺反应合成月桂酰二乙醇胺。
对月桂酸甲酯与二乙醇胺反应条件进行优化，其优化条件为：反应温度170℃、反应时间60 min、催化剂用量为月桂酸甲酯质量的1%，脂胺摩尔比为1.6∶1。
迷迭香酸对过氧化氢处理下的皮肤黑色素瘤的抗氧化作用(原文翻译)
迷迭香酸（罗丹酚酸）对H2O2处理过的皮肤黑色素瘤细胞的抗氧化作用Sun Mi Yoo1 and Jeong Ran Kang2*1.韩国光州500-741号东冈大学美容系2.韩国首尔143-701号建国大学生物工程系2009.2.6收到 2009.4.17接收本学科旨在检测迷迭香酸对人工孵育的皮肤黑色素瘤细胞在ROS下的抗氧化作用。
通过XTT比色法，以细胞毒性和抗氧化作用来分析细胞粘附活性，DPPH自由基清除活性以及H2O2处理1-10h和未经处理的两种情况下乳酸脱氢酶的活性。
用20-110 μM 的H2O2处理皮肤黑色素瘤细胞5-7h后，细胞活性的降低呈剂量和时间依赖性。
通过XTT比色法测得H2O2的半抑制浓度（IC50 ）为90μM。
同时H2O2增强了LDH细胞的剂量依赖性。
用50-90μM的H2O2处理8h后测得LDH50为60 μM H2O2。
迷迭香酸能增强细胞活性和DPPH自由基清除活性，降低乳酸盐脱氢酶的活性。
细胞的H2O2处理证实了对人工孵育的皮肤黑色素瘤细胞的强抗氧化作用。
通过H2O2的处理，迷迭香酸能在细胞内能增强细胞活性和DPPH 自由基清除活性，降低乳酸盐脱氢酶的活性。
这被认为是迷迭香酸对ROS（ROS）如H2O2的抗氧化作用。
Key words：DPPH-radical scavenging, LDH, rosmarinic acid, XTT assay关键字：DPPH自由基清除活性，乳酸脱氢酶，迷迭香酸，XTT比色法据研究发现，ROS通过氧化应激对细胞的损伤和一些脑部疾病比如帕金森症或心脏疾病例如心肌梗塞之间有很大的关联[Difazio et al., 1992; Delanty and Dichter, 1998].尤其是研究人员认为ROS是皮肤老化的一个主要的因素后，一直试图从ROS方面研究衰老。
[Yokozawa et al., 1998].据研究表明，ROS的氧化应激会通过萎缩细胞引起各种疾病，例如超氧自由基、H2O2（H2O2）或羟基自由基的巯基蛋白反应中断酶的活性，破坏脱氧RMA（DNA）或RMA（RNA），诱导细胞膜脂质过氧化。
二氟尼柳美国药典
Diflunisal Tablets» Diflunisal Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of C13H8F2O3.Packaging and storage— Preserve in well-closed containers.USP Reference standards 11—USP Diflunisal RS.Identification—A: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that of the Standard preparation, obtained as directed in the Assay.B: Transfer a quantity of finely ground Tablets, equivalent to about 100 mg of diflunisal, to a 10-mL volumetric flask, add 2 mL of water, and sonicate for 5 minutes. Dilute with methanol to volume, sonicate for an additional 5 minutes, mix, and filter. Separately apply 10 µL each of the filtrate and a Standard solution of USP Diflunisal RS in methanol solution (4 in 5) containing 10 mg per mL to a thin-layer chromatographic plate (see Chromatography 62) coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram in a solvent system consisting of n-hexane, glacial acetic acid, and chloroform (17:3:2) until the solvent front has moved aboutthree-fourths of the length of the plate. Remove the plate from the chamber, air-dry, and examine under long-wavelength UV light: the RF value of the principal spot in the chromatogram of the test solution corresponds to that obtained from the Standard solution.Dissolution 71—pH 7.20, 0.1 M Tris buffer— Dissolve 121 g of tris (hydroxymethyl) aminome thane (THAM) in 9 liters of water. Adjust the solution with a 7 in 100 solution of anhydrous citric acid in water to a pH of 7.45, at 25. Dliters, equilibrate to 37, a H of 7.20, if necessary.Medium: pH 7.20, 0.1 M Tris buffer; 900 mL.Apparatus 2: 50 rpm.Time: 30 minutes.Procedure— Determine the amount of C13H8F2O3 dissolved from UV absorbances at the wavelength of maximum absorbance at about 306 nm of filtered portions of the solution under test, suitably diluted with pH 7.20, 0.1 M Tris buffer, in comparison with a Standard solution having a known concentration of USP Diflunisal RS in the same Medium.Tolerances— Not less than 80% (Q) of the labeled amount of C13H8F2O3 is dissolved in 30 minutes.Uniformity of dosage units 90: mProcedure for content uniformity—Transfer 1 finely powdered Tablet to a200-mL volumetric flask, add 50 mL of water, shake by mechanical means for 30 minutes, and sonicate for 2 minutes. Add 100 mL of alcohol to the flask, shake by mechanical means for 15 minutes, and sonicate for 2 minutes. Dilute with alcohol to volume, mix, and centrifuge a portion of the solution. Quantitatively dilute an accurately measured volume of the resultant clear supernatant with alcohol, if necessary, to obtain a test solution containing about 1.25 mg per mL. Transfer about 125 mg of USP Diflunisal RS, accurately weighed, to a 100-mL volumetric flask, add 75 mL of alcohol to dissolve, dilute with water to volume, and mix to obtain the Standard solution. Transfer 3.0 mL each of the Standard solution and the test solution to separate 50-mL volumetric flasks. To each flask add 5.0 mL of a solution containing 1 g of ferric nitrate in 100 mL of 0.08 N nitric acid, dilute with water to volume, and mix. Concomitantly determine the absorbances of the solutions at the wavelength of maximum absorbance at about 550 nm, with a suitable spectrophotometer, using water as the blank. Calculate the quantity, in mg, of C13H8F2O3 in the Tablet by the formula:(TC / D)(AU / AS)in which T is the labeled quantity, in mg, of diflunisal in the Tablet; C is the concentration, in µg per mL, of USP Diflunisal RS in the Standard solution; D is the concentration, in µg per mL, of diflunisal in the test solution, based uponthe labeled quantity per Tablet and the extent of dilution; and AU and AS are the absorbances of the solutions from the test solution and the Standard solution, respectively.Assay—Mobile phase—Prepare a suitable degassed mixture of water, methanol, acetonitrile, and glacial acetic acid (45:40:17:6) such that the retention time of diflunisal is about 8 minutes.Standard preparation— Dissolve a suitable quantity of USP Diflunisal RS in a mixture of acetonitrile and water (60:40) to obtain a solution having a known concentration of about 1.0 mg per mL.Assay preparation—Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of diflunisal, to a 100-mL volumetric flask containing about 5 mL of water. Sonicate for 5 minutes, add 60.0 mL of acetonitrile, sonicate for an additional 5 minutes, dilute with water to volume, mix, and filter.Chromatographic system (see Chromatography 62)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L1.The flow rate is about 2.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for the analyte peak is not more than 2.0, and the relative standard deviation for replicate injections is not more than 2.0%.Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of diflunisal (C13H8F2O3) in the portion of Tablets taken by the formula:100C(rU / rS)in which C is the concentration, in mg per mL, of USP Diflunisal RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.。
二氟尼柳及其中间体、衍生物的合成研究进展
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Abstract:A series of 2-(trifluoroacetamido)imidazo[1,2-a ]-pyridines was prepared and treated with phenyliodine(III) bis(tri-fluoroacetate) (PIFA) in the presence of a variety of thiols leading chemoselectively to the corresponding 3-sulfides. Exposure of these adducts to silica gel in MeOH/CH 2Cl 2provides a convenient method for the cleavage of the trifluoroacetamide group.Key words:chemoselective sulfenylation, phenyliodine(III)bis(trifluoroacetate), imidazopyridines, trifluoroacetamide hydrol-ysisImidazopyridines and analogues,1structurally related to benzimidazoles, have demonstrated significant potential in the search for new drugs.2Their pharmacological pro-file is critically dependent on the nature of the substitution at the 3-position.2Although sulfenyl, sulfinyl and sulfonyl groups have been recognised for their distinguishing fea-tures in structure–activity relationship studies,3a conve-nient approach to their incorporation in heterocyclic systems, such as imidazopyridines and analogues, re-mained unknown.Elegant approaches involving carbanions as intermedi-ates, such as halogen–metal exchange,4single electron transfer (SET) reactions mediated by aromatic anion rad-icals,5Rieke metals,6or the use of palladium-catalysed cross-coupling reactions,7suffer from the deficiency of chemoselectivity.We found an urgent need for a general, selective and con-vergent approach that would allow the introduction of a large variety of sulfur groups at C-3 of imidazopyridines (Scheme 1) and be compatible with the presence of substit-uents, such as iodo, chloro and methoxycarbonyl groups.Benzenesulfenyl chloride has been already employed in an electrophilic sulfenylation of imidazo[1,2-a ]pyridine.2e However, the reported yield was only 22% and the limited number of the commercially available sulfenyl chlorides precludes a structure–activity relationship investigation.In a recent report, Kita’s reagent, phenyliodine(III) bis(tri-fluoroacetate) (PIFA), has been described as an efficient mediator for the direct substitution of phenol ethers by various thiophenols.8Herein, we wish to report a new ap-plication of this reagent in the sulfenylation of function-alised imidazopyridmes.9For this investigation, we have designed and synthesised the imidazopyridines 4a–c which differ by the type of functionality at the 6-position in order to permit further transformations.The synthesis of 4a–c is outlined in Scheme 2. Reaction of aminopyridines 110with p -toluenesulfonyl chloride inpyridine using the classical procedure and subsequent treatment of the pyridin-2(1H )-imine 2with iodoacet-amide in the presence of Hünig’s base (i -Pr 2NEt) in DMF provided the corresponding carboxamides 3a–c in good yield. In our hands, the use of Hünig’s base instead of the reported NaH 2e considerably enhanced the yield of the alkylation. We were unable to detect the exo-alkylated isomer that was reported to be the major product when the reaction was performed in the presence of NaH.2e Conver-sion of 3a–c to the desired 2-(trifluoroacetamido)imid-azopyridines 4a–c was accomplished by treatment with trifluoroacetic anhydride.11Chemoselective Arylsulfenylation of 2-Aminoimidazo[1,2-a ]pyridines by Phenyliodine(III) Bis(trifluoroacetate) (PIFA)Chafiq Hamdouchi,* Concha Sanchez, Jesús EzquerraCentro de Investigación Lilly, S. A. Paraje de la Cruz S/N, E-28130 Valdeolmos, Madrid, Spain E-mail: Hamdouchi_Chafiq@Received 6 October 1997; revised 17 November 1997Scheme 1Scheme 2The sulfenylation of imidazo[1,2-a ]pyridines 4a–c medi-ated by the hypervalent iodine(III) reagent, phenylio-dine(III) bis(trifluoroacetate) (PIFA), was investigated using a variety of thiols. It should be noted that when the thiol was injected into the mixture of imidazopyridine/PIFA in 1,1,1,3,3,3-hexafluoropropan-2-ol, the reaction failed to give the sulfenylated product. The PIFA should be added after dissolving or suspending the substrate and the thiol in hexafluoropropanol.In conclusion, a direct and chemoselective sulfenylation of imidazopyridine at C-3 has been developed. The high yield observed in the examples reported, and the compat-ibility with sensitive functions present in the molecule,promise its application for the incorporation of sulfur groups into a variety of heterocyclic analogues. A conve-nient method for the hydrolysis of the appropriate trifluo-roacetamides has also been described.All reagents were purchased from Aldrich and used without further purification unless otherwise stated. Column chromatography was carried out on flash silica gel (Merck 230–400 mesh). TLC analysis was conducted on Whatman silica gel plates. 1H and 13C NMR spectra were recorded at 200 MHz with DMSO-d 6or CDCl 3as solvent with a Bruker AC-200 instrument. Chemicals shifts (d values) and cou-pling constants (J values) are given in ppm and Hz respectively. C as-signments were realised by DEPT and HMQC experiments. MS were recorded on a VG-Autospec mass spectrometer.5-Chloro-N -tosylpyridin-2(1H )-imine (2a):5-Chloropyridin-2-amine (1a ) (10 g, 77.78 mmol) was dissolved in anhyd pyridine (60 mL). TsCl (16.31 g, 85.56 mmol) was added and the solution was heated at 80–90°C under argon overnight. Pyridine was removed in vacuo to give a white solid. Water (1.5 L) was added and the mixture was stirred for 90 min. The white solid was collected,dried in vacuo and then crystallised (EtOAc, 200 mL) to give 21.2 g (96%) of 2a as a white solid; mp 176°C (EtOAc).1H NMR (200 MHz, CDCl 3): d = 2.39 (s, 3H), 7.41 (d,1H, J 34= 8.6Hz, H 3), 7.47 (AA ¢BB ¢system, 4H, J = 8.4 Hz, Ar H ), 7.62 (dd, 1H,J 34=8.6 Hz, J 46= 2.5 Hz, H 4), 8.39 (d, 1H, J 46= 2.5 Hz, H 6).13C NMR (50 MHz, DMSO-d 6): d = 21.0 (Me ), 113.2, 125.0, 127.1,129.6, 137.2, 138.3, 143.5, 146.2, 150.1.MS (EI +): m/z (%) = 284.04 (M ++ 2, 2.0), 282.04 (M +, 5.6), 217.0(100.0).Table 1.Reaction of 4a–c with Arenethiols in the Presence of PIFA Substrate Ar Time Compound Yield (h)(%)4a Ph4.5 6a 774a 4-ClC 6H 4 4 7a 724a 4-FC 6H 458a 964a 4-MeOC 6H 4 4.5 9a 914a 4-NO 2C 6H 4 4.5 10a 04a 3-ClC 6H 420 11a 694b Ph4.5 6b 844b 4-ClC 6H 4 4 7b 754b 4-FC 6H 45 8b 734b 4-MeOC 6H 4 4.5 9b 824b 4-NO 2C 6H 4 4.5 10b 04c Ph4.5 6c 834c 4-ClC 6H 4 4 7c 804c 4-FC 6H 45 8c 744c 4-MeOC 6H 4 4.5 9c 824c 4-NO 2C 6H 4 4 10c 04c3-ClC 6H 4411c87Scheme 3SchemeAs noted in Table 1, a series of sulfenylated imidazopyri-dine derivatives was prepared via reaction of the imid-azopyridine with the appropriate and commercially available thiol in the presence of PIFA. Substrates 4a–c were converted to the corresponding sulfides 6a–11a , 6b–9b , and 6c–11c in high yield. Only p -nitrobenzenethiol failed to react and the starting material was recovered un-changed. It should be emphasised that neither the ester function in the substrate 4c nor the halogen in substrates 4a and 4b were affected during the sulfenylation process.All attempts to detrifluoroacetylate compounds 7a ,11a ,7b ,7c ,11c , and 8c using strongly basic conditions such as NaOH or Hünig’s base failed to yield the respective amines 12a ,13a ,12b ,12c ,13c , and 14c . Instead, the re-action led to imidazo ring opening providing the aminopy-ridine as the main product (Scheme 4). Surprisingly, the trifluoro-acetamide group was hydrolysed when support-ed on silica gel in a mixture of MeOH/CH 2Cl 2(2:98) in good yield (Table 2).Table 2.Hydrolysis of Trifluoroacetamides in the Presence of Silica Gel (Scheme 4)Substrate R 6ArCompound Yield (%)7a Cl 4-ClC 6H 412a 7011a Cl 3-ClC 6H 413a 727b I 4-ClC 6H 412b 817c CO 2Me 4-ClC 6H 412c 8811c CO 2Me3-ClC 6H 413c 658cCO 2Me 4-FC 6H 414c555-Iodo-N-tosylpyridin-2(1H)-imine (2b):Compound 2b was prepared as described for 2a, starting from 5-io-dopyridin-2-amine6(1b). 2b was isolated as a brown solid in 85% yield; mp 205°C (EtOAc).1H NMR (200 MHz, DMSO-d6): d= 2.34 (s, 3H), 6.92 (d, 1H, J34=8.7 Hz, H3), 7.56 (AA¢BB¢system, 4H, J= 8.1 Hz, Ar H), 7.98 (d, 1H, J34= 8.7 Hz, J46= 2.2 Hz, H4), 8.34 (d, 1H, J46= 2.2 Hz, H6), 11.23 (bs, 1H, N H).13C NMR (50 MHz, DMSO-d6): d= 21.2 (Me), 85.6 (C5), 114.3,127.3, 129.8, 137.4, 143.6, 146.4, 150.9, 153.3.MS (FAB+): m/z= 374.9 (M + H)+, calcd 374.2.5-(Methoxycarbonyl)-N-tosylpyridin-2(1H)-imine (2c): Compound 2c was prepared as described for 2a, starting from 5-(methoxycarbonyl)pyridin-2-amine (1c).2c was isolated as a white solid in 93% yield; mp 214°C (EtOAc).1H NMR (200 MHz, DMSO-d6): d= 2.33 (s, 3H, Ar Me), 3.79 (s, 3H,CO2Me), 7.15 (d, 1H, J34= 8.9 Hz, H3), 7.58 (AA¢BB¢system, 4H, J = 8.2 Hz, Ar H), 8.12 (dd, 1H, J46= 2.2 Hz, J34= 8.9 Hz, H4), 8.57 (d, 1H, J46= 2.2 Hz, H6), 12.06 (bs, 1H, N H).13C NMR (50 MHz, DMSO-d6): d= 21.0 (Ar Me), 52.1 (CO2Me),112.0, 118.6, 127.1, 129.6, 137.5, 139.6, 143.4, 147.6, 155.1, 164.5 (C O2Me).1-(Carbamoylmethyl)-6-(methoxycarbonyl)-N-tosylpyridin-2(1H)-imine (3c):i-Pr2NEt (125.2 mL, 71.82 mmol) was added to a suspension of 2c(20 g, 65.3 mmol) in anhyd DMF (120 mL) under argon. To the resulting solution was added 2-iodoacetamide (13.28 g, 71.82 mmol) and the mixture was stirred at r.t. for 24 h. The solution was poured onto water (60 mL) and stirred for 90 min. The solid was collected by filtration and washed with water (1 L) then with Et2O (200 mL) and dried in vacuo to give 3c as a white solid; yield: 21.76 g (92%).1H NMR (200 MHz, DMSO-d6): d= 2.34 (s, 3H), 3.82 (s, 3H,CO2Me), 4.89 (s, 2H), 7.39 (d, 1H, J34= 9.5 Hz, H3), 7.39 (bs, 1H, N H), 7.47 (AA¢BB¢system, 4H, J= 8.1 Hz, Ar H), 7.79 (bs, 1H, N H), 8.07 (dd, 1H, J34= 9.5 Hz, J46= 2.2 Hz, H4), 8.73 (d, 1H, J46= 2.2 Hz, H6).13C NMR (50 MHz, DMSO-d6): d= 20.9 (Me), 52.3 (Me), 54.7(CH2), 112.6, 115.6 (CH), 125.9 (CH), 129.2 (CH), 139.6 (CH), 140.3, 141.8, 146.1 (CH), 156.1, 163.6 (C O2Me), 167.2 (C ONH2). MS (FAB+): m/z= 364.1 (M + H)+, calcd 363.4.1-(Carbamoylmethyl)-6-chloro-N-tosylpyridin-2(1H)-imine(3a):Compound 3a was prepared as described for 3c, starting from 2a.3a was isolated as a white solid in 85% yield.1H NMR (200 MHz, DMSO-d6): d= 2.32 (s, 3H), 4.78 (s, 2H), 7.32(d, 1H, J34= 9.7 Hz, H3), 7.43 (bs, 1H, N H), 7.45 (AA¢BB¢system, 4H, J= 8.1 Hz, Ar H), 7.81 (bs, 1H, N H), 7.82 (dd, 1H, J34= 9.7 Hz, J46= 2.7 Hz, H4), 8.33 (d, 1H, J46= 2.7 Hz, H6).13C NMR (50 MHz, DMSO-d6): d= 20.9 (Me), 54.5 (CH2), 115.6,116.9, 125.9, 140.1, 140.5, 141.5, 154.1, 167.1 (C ONH2).MS (EI+): m/z(%) = 341.1 (M++ 2, 6.4), 339.1 (M+, 17.4), 91 (100.0). 1-(Carbamoylmethyl)-6-iodo-N-tosylpyridin-2(1H)-imine (3b): Compound 3b was prepared as described for 3c, starting from 2b.3b was isolated as a brown solid in 86% yield; mp 246.7–247.5°C.1H NMR (200 MHz, DMSO-d6): d= 2.32 (s, 3H), 4.75 (s, 2H), 7.15(d, 1H, J34= 9.5 Hz, H3), 7.38 (bs, 1H, N H), 7.43 (AA¢BB¢system, 4H, J= 8.2 Hz, Ar H), 7.77 (bs, 1H, N H), 7.90 (dd, 1H, J34= 9.5 Hz, J46= 2.2 Hz, H4), 8.35 (d, 1H, J46= 2.2 Hz, H6).13C NMR (50 MHz, DMSO-d6): d= 20.9 (Me), 54.2 (CH2), 71.6(C5), 117.6 (CH), 125.9 (CH), 129.2 (CH), 140.6, 141.5, 146.5 (CH), 148.3, 154.2, 167.3 (C ONH2).MS (FAB+): m/z= 432.0 (M + H)+, calcd 432.2.6-(Methoxycarbonyl)-2-(trifluoroacetamido)imidazo[1,2-a]pyri-dine (4c):Compound 3c(5 g, 13.76 mmol) in anhyd CH2Cl2(75 mL) was dis-solved in TFAA and the solution was refluxed for 3 h. Solvents were removed in vacuo and the solid was suspended in EtOAc (150 mL). After stirring for 30 min, the solid was collected and again stirred in water (50 mL) for 30 min. The solid was collected and dried in vacuo to give 1.92 g (49%) of 4c as a white solid; mp 216.2–217.9°C.1H NMR (300 MHz, DMSO-d6): d= 3.88 (s, 3H), 7.57 (dd, 1H, J58= 0.7 Hz, J78= 9.5 Hz, H8), 7.69 (dd, 1H, J57= 1.7 Hz, J78= 9.5 Hz, H7), 8.41 (s, 1H, H3), 9.38 (dd, 1H, J57= 1.7 Hz, J58= 0.7 Hz, H5).13C NMR (75 MHz, DMSO-d6, assigned by HMQC experiment): d= 52.3 (Me), 103.8 (C3), 115.2 (C8), 115.5 (q, J CF= 287.7 Hz, CO C F3), 115.6, 124.3 (C7), 131.2 (C5), 140.6, 141.9, 154.1 (q, J CF= 39.0 Hz, C OCF3), 164.8 (C O2Me).MS (FAB+): m/z= 288.1 (M + H)+, calcd 288.0.6-Chloro-2-(trifluoracetamido)imidazo[1,2-a]pyridine (4a): Compound 4a was prepared as described for 4c, starting from 3a. After 5 h 4a was isolated as a white solid in 76% yield (25 mL of EtOAc were required for 2.09 g of 3a and 50 mL of water); mp 243.9–244.5°C (EtOAc).1H NMR (200 MHz, DMSO-d6): d= 7.33 (dd, 1H, J57= 2.1 Hz, J78 = 9.5 Hz, H7), 7.55 (d, 1H, J78= 9.5 Hz, H8), 8.24 (s, 1H, H3), 8.88 (d, 1H, J57= 2.1 Hz, H5), 12.54 (bs, 1H, N H).13C NMR (50 MHz, DMSO-d6): d= 103.4 (C3), 115.7 (q, J CF= 287.3 Hz, CO C F3), 116.6 (CH), 119.1, 125.0 (CH), 126.1 (CH), 139.8, 140.1, 154.1 (q, J CF= 38.5 Hz, C OCF3).MS (FAB+): m/z= 264.0 (M + H)+, calcd 264.0.Anal. Calcd for C9H5ClF3N3O·0.33 H2O: C, 40.09; H, 2.12; N, 15.58. Found: C, 40.12; H, 2.13; N, 15.07.6-Iodo-2-(trifluoroacetamido)imidazo[1,2-a]pyridine (4b): Compound 4b was prepared as described for compound 4c, starting from 3b. After 5 h, 4b was isolated as a white solid in 63% yield (8 mL of EtOAc were required for 0.751 g of 3b and 50 mL of water); mp 247°C (EtOAc).1H NMR (200 MHz, DMSO-d6): d= 7.35 (dd, 1H, J58= 0.9 Hz, J78= 9.3 Hz, H8), 7.47 (dd, 1H, J57= 1.6 Hz, J78= 9.3 Hz, H7), 8.19 (s, 1H, H3), 8.96 (dd,1H, J58= 0.9 Hz, J57= 1.6 Hz, H5), 12.50 (bs,1H, N H). 13C NMR (50 MHz, DMSO-d6): d= 76.0 (C6), 102.6 (C3), 115.7 (q, J CF= 287.3 Hz, CO C F3), 117.1 (CH), 131.7 (CH), 132.9 (CH), 139.5 (C2or C9), 139.9 (C9or C2), 154.1 (q, J CF= 37.9 Hz, C OCF3).MS (FAB+): m/z= 356.0 (M + H)+, calcd 355.9.Anal. Calcd for C9H5F3IN3O·0.25 H2O: C, 30.06; H, 1.54; N, 11.69. Found: C, 30.11; H, 1.65; N, 11.45.Sulfenylation at the 3-Position; General Procedure:PIFA(1.5 equiv) was added to a stirred solution (or suspension) of imidazo[1,2-a]pyridine 4a–c(50 mg) and arenethiol (2 equiv) in 1,1,1,3,3,3-hexafluoropropan-2-ol (1 mL) at r.t. under argon. The mixture was stirred for several hours (see Table). The solvents were removed and the resulting solid was dissolved in CH2Cl2(15 mL) and washed with brine. After drying (Na2SO4) the solvent was removed. The solid was washed with CH2Cl2or CH2Cl2/hexane (1:1) to give the sulfenylated material as a white solid in its pure form.6-Chloro-3-(phenylthio)-2-(trifluoroacetamido)imidazo[1,2-a]pyridine (6a): isolated in 77% yield after washing with CH2Cl2/hexane (1:1). 1H NMR (200 MHz, CDCl3): d= 6.91–6.97 (m, 2H, Ar H), 7.14–7.20 (m, 3H, Ar H), 7.30 (dd, 1H, J57= 2.0 Hz, J78= 9.5 Hz, H7), 7.59 (d, 1H, J78 = 9.5 Hz, H8), 8.13 (d, 1H, J57= 2.0 Hz, H5), 8.84 (bs, 1H, N H).13C NMR (50 MHz, DMSO-d6): d= 105.7 (C3), 115.7 (q, J CF= 288.6 Hz, CO C F3), 118.3, (CH), 121.5 (CH), 122.5 (CH), 126.8 (CH), 128.5 (CH), 133.1 (CH), 133.1, 143.0, 144.1, 155.8 (q, J CF= 37.0 Hz, C OCF3).MS (FAB+): m/z= 372.1 (M + H)+, calcd 371.0.Anal. Calcd for C 15H 9ClF 3N 3OS ·0.2 H 2O: C, 48.46; H, 2.44; N, 11.3.Found: C, 48.31; H, 2.56; N, 11.03.6-Iodo-3-(phenylthio)-2-(trifluoroacetamido)imidazo[1,2-a ]pyridine (6b ): isolated in 84% yield after washing with CH 2Cl 2/hexane (1:1).1H NMR (200 MHz, CDCl 3): d = 6.85–6.98 (m, 2H, Ar H ), 7.12–7.26(m, 3H, Ar H ), 7.41 (dd, 1H, J 58= 0.7 Hz, J 78= 9.4 Hz, H 8), 7.49 (dd,1H, J 57= 1.6 Hz, J 78= 9.4 Hz, H 7), 8.32 (m, 1H, H 5), 9.05 (bs, 1H,N H ).13C NMR (50 MHz, DMSO-d 6): d = 78.9 (C 6), 104.6 (C 3), 115.9 (q,J CF = 286.5 Hz, CO C F 3), 118.6 (CH), 126.6 (CH), 126.7 (CH), 128.9(CH), 129.6 (CH), 133.2, 135.3 (CH), 143.2, 143.8, 155.8 (q, J CF =35.9 Hz, C OCF 3).MS (FAB +): m/z = 464.0 (M + H)+, calcd 463.9.Anal. Calcd for C 15H 9F 3IN 3OS: C, 38.59; H, 2.03; N, 9.00. Found: C,38.69; H, 2.16; N, 8.63.6-(Methoxycarbonyl)-3-(phenylthio)-2-(trifluoracetamido)imid-azo[1,2-a ]pyridine (6c ): isolated in 83% yield after washing with CH 2Cl 2/hexane (1:1).1H NMR (200 MHz, CDCl 3): d = 3.86 (s, 3H, CO 2Me ), 6.93–6.98 (m,2H, Ar H ), 7.13–7.24 (m, 3H, Ar H ), 7.66 (dd, 1H, J 58= 0.9 Hz, J 78=9.4 Hz, H 8), 7.88 (dd, 1H, J 57= 1.7 Hz, J 78= 9.4 Hz, H 7), 8.80 (bs,1H, N H ), 8.83 (dd, 1H, J 57= 1.7 Hz, J 78= 9.4 Hz, H 5).13C NMR (50 MHz, DMSO-d 6): d = 52.7 (CO 2Me ), 106.0 (C 3), 115.8(q, J CF = 288.6 Hz, CO C F 3), 117.2 (CH), 117.3, 126.4 (CH), 126.5(CH), 126.8 (CH), 127.4 (CH), 129.7 (CH), 133.1, 145.2, 145.3,155.7 (q, J CF = 37.5 Hz, C OCF 3), 164.2 (C O 2Me).MS (FAB +): m/z = 396.1 (M + H)+, calcd 396.1.Anal. Calcd for C 17H 12F 3N 3O 3S: C, 51.64; H, 3.06; N, 10.63. Found:C, 51.58; H, 3.14; N, 10.70.6-Chloro-3-(4-chlorophenylthio)-2-(trifluoroacetamido)imid-azo[1,2-a ]pyridine (7a ): isolated in 72% yield after washing with CH 2Cl 2.1H NMR (200 MHz, CDCl 3): d = 7.03 (AA ¢BB ¢system, 4H, J = 8.7Hz, Ar H ), 7.32 (dd, 1H, J 57= 2.0 Hz, J 78= 9.5 Hz, H 7), 7.59 (dd, 1H,J 58= 0.8 Hz, J 78= 9.5 Hz, H 8), 8.09 (dd, 1H, J 57= 2.0 Hz, J 58=0.8 Hz, H 5), 8.79 (bs, 1H, N H ).13C NMR (50 MHz, DMSO-d 6): d = 105.1 (C 3), 115.8 (q, J CF =285.0 Hz, CO C F 3), 118.4, (CH), 121.6 (CH), 122.5 (CH), 128.4(CH), 128.7 (CH), 129.4 (CH), 131.4, 132.4, 143.2, 144.3, 155.8 (q,J CF = 38.3 Hz, C OCF 3).MS (FAB +): m/z = 406.0 (M + H)+, calcd 406.0.Anal. Calcd for C 15H 8Cl 2F 3N 3OS ·0.2 H 2O: C, 43.96; H, 2.07; N,10.25. Found: C, 43.97; H, 2.37; N, 9.95.3-(4-Chlorophenylthio)-6-iodo-2-(trifluoroacetamido)imidazo[1,2-a ]pyridine (7b ): isolated in 75% yield after washing with CH 2Cl 2.1H NMR (200 MHz, DMSO-d 6): d = 7.20 (AA ¢BB ¢system, 4H, J =8.6 Hz, Ar H ), 7.58 (dd, 1H, J 78= 9.4 Hz, H 8), 7.73 (dd, 1H, J 57=1.6 Hz, J 78= 9.4 Hz, H 7), 8.47 (m, 1H, H 5), 11.93 (bs, 1H, N H ).13C NMR (50 MHz, DMSO-d 6): d = 79.6 (C 6), 104.0 (C 3), 115.8 (q,J CF = 285.7 Hz, CO C F 3), 118.6 (CH), 128.2 (CH), 129.0 (CH), 129.5(CH), 131.4, 132.5, 135.5 (CH),143.4, 143.7, 155.8 (q, J CF = 38.1 Hz,C OCF 3).MS (FAB +): m/z = 497.9 (M + H)+, calcd 497.9.Anal. Calcd for C 15H 8ClF 3IN 3OS ·0.25 H 2O: C, 35.88; H, 1.71; N,8.37. Found: C, 35.92; H, 1.72; N, 8.07.3-(4-Chlorophenylthio)-6-(methoxycarbonyl)-2-(trifluoroacetami-do)imidazo[1,2-a ]pyridine (7c ): isolated in 80% yield after washing with CH 2Cl 2.1H NMR (200 MHz, CDCl 3): d = 3.98 (s, 3H, CO 2Me ), 7.04 (AA ¢BB ¢system, 4H, J = 8.6 Hz, Ar H ), 7.65 (dd, 1H, J 58= 1.0 Hz, J 78= 9.4 Hz,H 8), 7.90 (dd, 1H, J 57= 1.7 Hz, J 78= 9.4 Hz, H 7), 8.81 (dd, 1H, J 57=1.7 Hz, J 58= 1.0 Hz, H 5), 10.15 (bs, 1H, N H ).13C NMR (50 MHz, DMSO-d 6): d = 52.7 (CO 2Me ), 105.2 (C 3), 115.8(q, J CF = 286.0 Hz, CO C F 3), 117.3, 117.5 (CH), 126.6 (CH), 127.4(CH), 128.0 (CH), 129.6 (CH), 131.4, 132.4, 145.4, 155.3 (q, J CF =37.5 Hz, C OCF 3), 164.2 (C O 2Me).MS (FAB +): m/z = 430.0 (M + H)+, calcd 430.1.Anal. Calcd for C 17H 11ClF 3N 3O 3S ·1 H 2O: C, 45.59; H, 2.93 ; N, 9.38.Found: C, 45.54; H, 2.56; N, 9.05.6-Chloro-3-(4-fluorophenylthio)-2-(trifluoroacetamido)imidazo[1,2-a ]pyridine (8a ): isolated in 96% yield after washing with CH 2Cl 2/hexane (1:1).1H NMR (200 MHz, CDCl 3): d = 6.86–7.03 (m, 4H, Ar H ), 7.30 (dd,1H, J 57= 2.0 Hz, J 78= 9.5 Hz, H 7), 7.58 (dd, 1H, J 58= 0.7 Hz, J 78=9.5 Hz, H 8), 8.13 (dd, 1H, J 57= 2.0 Hz, J 58= 0.7 Hz, H 5), 8.69 (bs,1H, NH).13C NMR (50 MHz, DMSO-d 6): d = 106.3 (C 3), 115.8 (q, J CF = 288.2Hz, CO C F 3), 116.6 (d, CH, J CF = 22.2 Hz), 118.3 (CH), 118.7, 121.6,122.6 (CH), 128.5 (CH), 129.6 (d, CH, J CF = 8.1 Hz), 143.0, 143.9,155.9 (q, J CF = 37.5 Hz, C OCF 3), 161.3 (d, J CF = 244.6 Hz).MS (FAB +): m/z = 390.1 (M + H)+, calcd 390.1.Anal. Calcd for C 15H 8ClF 4N 3OS: C, 45.80; H, 2.15; N, 10.68. Found:C, 45.70; H, 2.17; N, 10.66.3-(4-Fluorophenylthio)-6-iodo-2-(trifluoroacetamido)imidazo[1,2-a ]pyridine (8b ): isolated in 73% yield after washing with CH 2Cl 2.1H NMR (200 MHz, CDCl 3): d = 6.87–7.02 (m, 4H), 7.41 (dd, J 58=0.9 Hz, J 78= 9.3 Hz, 1H, H 8), 7.52 (dd, J 57= 1.6 Hz, J 78= 9.3 Hz, 1H,H 7), 8.33 (dd, J 57= 1.6 Hz, J 58= 0.9 Hz, 1H, H 5), 8.71 (bs, 1H).13C NMR (50 MHz, DMSO-d 6): d = 79.0 (C 6), 105.1 (C 3), 115.8 (q,J CF = 286.5 Hz, CO C F 3), 116.6 (d, J CF = 22.3 Hz), 118.6 (CH), 128.6(d, J CF = 3.0 Hz), 128.9 (CH), 129.4 (d, J CF = 8.2 Hz), 134.5 (CH),143.2, 143.3, 155.8 (q, J CF = 37.0 Hz, C OCF 3), 161.2 (d, J CF = 244.1Hz).MS (FAB +): m/z = 482.1 (M + H)+, calcd 481.9.Anal. Calcd for C 15H 8F 4IN 3OS: C, 37.00; H, 1.79; N, 8.62. Found: C,36.94; H, 1.82; N, 8.44.3-(4-Fluorophenylthio)-6-(methoxycarbonyl)-2-(trifluoroacetami-do)imidazo[1,2-a ]pyridine (8c ): isolated in 74% yield after washing with CH 2Cl 2.1H NMR (200 MHz, CDCl 3): d = 3.87 (s, 3H, CO 2Me ), 6.86–7.06 (m,4H, Ar H ), 7.64 (dd, 1H, J 58= 0.9 Hz, J 78= 9.4 Hz, H 8), 7.89 (dd, 1H,J 57= 1.7 Hz, J 78= 9.4 Hz, H 7), 8.85 (dd, 1H, J 57= 1.7 Hz, J 58=0.9 Hz, H 5), 8.88 (bs,1H, N H ).13C NMR (50 MHz, DMSO-d 6): d = 52.7 (CO 2Me ), 106.4 (C 3), 115.8(q, J CF = 288.6 Hz, CO C F 3), 116.8 (d, CH, J CF = 18.3 Hz), 117.3(CH), 117.4, 126.5 (CH), 127.4 (CH), 128.5 (d, J CF = 2.2 Hz), 129.0(d, CH, J CF = 8.2 Hz), 145.0, 145.3, 155.7 (q, J CF = 38.5 Hz, C OCF 3),161.2 (d, J CF = 244.2 Hz), 164.3 (C O 2Me).MS (FAB +): m/z = 414.1 (M + H)+, calcd 414.1.Anal. Calcd for C 17H 11F 4N 3O 3S: C, 48.34; H, 2.86; N, 9.90. Found:C, 48.45; H, 2.58; N, 9.89.6-Chloro-3-(4-methoxyphenylthio)-2-(trifluoroacetamido)imid-azo[1,2-a ]pyridine (9a ): isolated in 91% yield after washing with CH 2Cl 2/hexane (1:1).1H NMR (200 MHz, DMSO-d 6): d = 3.69 (s, 3H, O Me ), 7.04 (AA ¢BB ¢system, 4H, J = 8.8 Hz, Ar H ), 7.54 (dd, 1H, J 57= 1.9 Hz, J 78= 9.4 Hz,H 7), 7.76 (d, 1H, J 78= 9.4 Hz, H 8), 8.50 (d, 1H, J 57= 1.9 Hz, H 5),11.92 (bs, 1H, N H ).13C NMR (50 MHz, DMSO-d 6): d = 55.2 (O Me ), 107.9 (C 3), 115.2(CH), 115.3 (q, J CF = 286.0 Hz, CO C F 3), 118.3, (CH), 121.3, 122.5(CH), 122.8, 128.2 (CH), 130.4, (CH), 142.6, 143.4, 155.9 (q, J CF =36.8 Hz, C OCF 3), 158.9.MS (FAB +): m/z = 402.1 (M + H)+, calcd 402.0.6-Iodo-3-(4-methoxyphenylthio)-2-(trifluoroacetamido)imidazo[1,2-a]pyridine(9b): isolated in 82% yield after washing with CH2Cl2/ hexane (1:1).1H NMR (200 MHz, DMSO-d6): d= 3.69 (s, 3H, O Me), 7.00 (AA¢BB¢system, 4H, J= 8.8 Hz, Ar H), 7.55 (d, 1H, J78= 9.4 Hz, H7), 7.69 (dd, 1H, J57= 1.6 Hz, J78= 9.4 Hz, H8), 8.52 (m, 1H, H5), 11.90 (bs, 1H, N H).13C NMR (50 MHz, DMSO-d6): d= 55.3 (O Me), 78.8 (C6), 106.7(C3), 115.3 (CH), 115.9 (q, J CF= 286.5 Hz, CO C F3), 118.6 (CH), 122.9, 128.9 (CH), 130.2 (CH), 135.0 (CH), 142.6, 142.8, 155.7 (q, J CF= 37.6 Hz, C OCF3), 158.8.MS (FAB+): m/z= 494.0 (M + H)+, calcd 493.9.Anal. Calcd for C16H11F3IN3O2S: C, 35.70; H, 3.00; N, 7.81. Found: C, 35.90; H, 2.20; N, 7.84.6-(Methoxycarbonyl)-3-(4-methoxyphenylthio)-2-(trifluoroacetami-do)imidazo[1,2-a]pyridine(9c): isolated in 82% yield after washing with CH2Cl2/hexane (1:1).1H NMR (200 MHz, DMSO-d6): d= 3.68 (s, 3H, O Me), 3.86 (s, 3H,CO2Me), 7.01 (AA¢BB¢system, 4H, J= 8.6 Hz, Ar H), 7.79 (d, 1H, J78 = 9.4 Hz, H8), 7.87 (dd, 1H, J57= 1.3 Hz, J78= 9.4 Hz, H7), 8.79 (m, 1H, H5), 12.02 (bs,1H, N H).13C NMR (50 MHz, DMSO-d6): d= 52.7 (CO2Me), 55.2 (O Me),108.0 (C3), 115.4 (CH), 115.9 (q, J CF= 288.6 Hz, CO C F3), 117.3 (CH), 122.9, 126.2 (CH), 127.5 (CH), 129.8 (CH), 144.4, 144.9, 155.8 (q, J CF= 37.4 Hz, C OCF3), 158.8, 164.3 (C O2Me).MS (FAB+): m/z= 426.1 (M + H)+, calcd 426.1.Anal. Calcd for C18H14F3N3O4S: C, 50.29; H, 3.40; N, 9.77. Found: C, 50.25; H, 3.17; N, 9.58.6-Chloro-3-(3-chlorophenylthio)-2-(trifluoroacetamido)imid-azo[1,2-a]pyridine(11a): isolated in 69% yield after washing with hexane.1H NMR (200 MHz, CDCl3): d= 6.77–6.83 (m, 1H, Ar H), 6.92–6.94(m, 1H, ArH), 7.10–7.14 (m, 2H, ArH), 7.33 (dd, 1H, J57= 2.0 Hz, J78 = 9.5 Hz, H7), 7.61 (dd, 1H, J58= 0.8 Hz, J78= 9.5 Hz, H8), 8.11 (dd, 1H, J57= 2.0 Hz, J58= 0.8 Hz, H5), 8.96 (bs, 1H, N H).13C NMR (50 MHz, DMSO-d6): d= 104.6 (C3), 115.8 (q, J CF=288.1 Hz, CO C F3), 118.4 (CH), 121.7, 122.7 (CH), 125.1 (CH), 126.0 (CH), 126.7 (CH), 128.8 (CH), 131.0 (CH), 134.1, 135.8, 143.2, 144.5, 155.8 (q, J CF= 37.9 Hz, C OCF3).MS (FAB+): m/z= 406.1 (M + H)+, calcd 406.0.Anal. Calcd for C15H8Cl2F3N3OS: C, 44.07; H, 2.04; N, 10.28. Found: C, 44.08; H, 2.09; N, 10.04.3-(3-Chlorophenylthio)-6-(methoxycarbonyl)-2-(trifluoroacetami-do)imidazo[1,2-a]pyridine(11c): isolated in 87% yield after washing with CH2Cl2.1H NMR (200 MHz, CDCl3): d= 3.87 (s, 3H, CO2Me), 6.83–6.88 (m,1H, Ar H), 6.95–6.97 (m, 1H, Ar H), 7.06–7.11(m, 1H, Ar H), 7.62 (dd, 1H, J58= 0.8 Hz, J78= 9.3 Hz, H8), 7.92 (dd, 1H, J57= 1.7 Hz, J78= 9.3 Hz, H7), 8.81 (dd, 1H, J57= 1.7 Hz, J58= 0.8 Hz, H5), 10.52 (bs,1H, N H).13C NMR (50 MHz, CDCl3): d= 52.8 (CO2Me), 103.5 (C3), 115.7 (q,J CF= 287.5 Hz, CO C F3), 116.8, 118.3, 124.4, 126.1, 127.2, 127.6, 127.9, 130.6, 135.3, 135.5, 145.6, 146.0, 154.9 (q, J CF= 39.0 Hz, C OCF3), 164.5 (C O2Me).MS (FAB+): m/z= 430.0 (M + H)+, calcd 430.0.Hydrolysis of Trifluoroacetamides; General Procedure:The respective imidazopyridine trifluoroacetamide derivative was dis-solved in CH2Cl2/MeOH (98:2, 15 mL). Silica gel was added to the so-lution. The mixture was stirred vigorously for 1–2 d. The conversion to the amine was followed by TLC (CH2Cl2/MeCN 4:1). The residue was filtered and the silica gel was washed with MeCN (10 mL). Removal of the solvents gave the desired compound as a pale-yellow solid.2-Amino-6-chloro-3-(4-chlorophenylthio)imidazo[1,2-a]pyridine (12a): isolated in 70% yield after column chromatography.1H NMR (200 MHz, CDCl3): d= 4.43 (bs, 2H, N H2), 7.06 (AA¢BB¢system, 4H, J= 8.6 Hz, Ar H), 7.07 (dd, 1H, J57= 2.0 Hz, J78= 9.3 Hz, H7), 7.34 (dd, 1H, J58= 0.8 Hz, J78= 9.5 Hz, H8), 8.05 (dd, 1H, J57= 2.0 Hz, J58= 0.8 Hz, H5).13C NMR (50 MHz, CDCl3): d= 89.9, 115.2 (CH), 120.2, 121.5 (CH), 126.6 (CH), 127.0 (CH), 129.4, (CH), 132.1, 133.9, 144.0, 157.0.2-Amino-3-(4-chlorophenylthio)-6-iodoimidazo[1,2-a]pyridine (12b): isolated in 81% yield after washing with hexane.1H NMR (200 MHz, DMSO-d6): d= 4.37 (bs, 2H, N H2), 6.99 (AA¢BB¢system, 4H, J= 8.5 Hz, Ar H), 7.11 (dd, 1H, J58= 0.6 Hz, J78 = 9.1 Hz, H8), 7.35 (dd, 1H, J57= 1.7 Hz, J78= 9.1 Hz, H7), 8.16 (dd, 1H, J57= 1.7 Hz, J58= 0.6 Hz, H5).13C NMR (50 MHz, CDCl3): d= 74.5 (C6), 86.7, 115.3 (CH), 126.9 (CH), 127.3 (CH), 129.3 (CH), 130.5, 133.2 (CH), 135.3, 144.1, 157.9.MS (FAB+): m/z= 402.0 (M + H)+, calcd 401.9.HRMS (FAB) calcd for C13H10ClN2S 401.932874, found 401.931500.2-Amino-3-(4-chlorophenylthio)-6-(methoxycarbonyl)imidazo[1,2-a]pyridine(12c): isolated in 88% yield after washing with hexane.1H NMR (200 MHz, CDCl3): d= 3.84 (s, 3H, CO2Me), 4.47 (bs, 2H, N H2), 7.00 (AA¢BB¢system, 4H, J= 8.7 Hz, Ar H), 7.33 (dd, 1H, J58 = 0.8 Hz, J78= 9.2 Hz, H8), 7.75 (dd, 1H, J57= 1.8 Hz, J78= 9.2 Hz, H7), 8.68 (dd, 1H, J57= 1.8 Hz, J58= 0.8 Hz, H5), 10.15 (bs, 1H, N H). 13C NMR (50 MHz, DMSO-d6): d= 51.7 (CO2Me), 87.2, 112.9 (CH), 114.4, 124.8 (CH), 125.2 (CH), 126.7 (CH), 129.0 (CH), 130.5, 134.7, 146.1, 158.8, 164.4 (C O2Me).MS (FAB+): m/z= 334.1 (M + H)+, calcd 334.0.HRMS (FAB) calcd for C15H13ClN3O2S 334.041701, found 334.042000.2-Amino-6-chloro-3-(3-chlorophenylthio)imidazo[1,2-a]pyridine (13a): isolated in 72% yield after column chromatography.1H NMR (200 MHz, CDCl3): d= 4.49 (bs, 2H, N H2), 6.74–6.79 (m, 1H, Ar H), 6.87–6.89 (m, 1H, Ar H), 7.00–7.07 (m, 2H, Ar H), 7.11 (dd, 1H, J57= 2.0 Hz, J78= 9.3 Hz, H7), 7.25 (dd, 1H, J58= 0.8 Hz, J78= 9.3 Hz, H8), 8.07 (dd, 1H, J57= 2.0 Hz, J58= 0.8 Hz, H5).13C NMR (50 MHz, CDCl3): d= 89.2, 115.1 (CH), 120.1, 121.5 (CH), 123.2 (CH), 124.9 (CH), 126.3 (CH), 127.1 (CH), 130.3, (CH), 135.3, 137.7, 144.1, 157.3.MS (FAB+): m/z= 310.1 (M + H)+, calcd 310.0.HRMS (FAB) calcd for C13H10NCl2N3S 309.997250, found 309.996300.2-Amino-3-(3-chlorophenylthio)-6-(methoxycarbonyl)imidazo[1,2-a]pyridine(13c): isolated in 65% yield after column chromatography. 1H NMR (200 MHz, CDCl3): d= 3.84 (s, 3H, CO2Me), 4.50 (bs, 2H, N H2), 7.00 (AA¢BB¢system, 4H, J= 8.6 Hz, Ar H), 7.33 (d, 1H, J78= 9.1 Hz, H8), 7.76 (dd, 1H, J57= 1.7 Hz, J78= 9.1 Hz, H7), 8.68 (d, 1H, J57= 1.7 Hz, H5).13C NMR (50 MHz, DMSO-d6): d= 52.7 (CO2Me), 87.2, 112.9 (CH), 114.4, 124.8 (CH), 125.2 (CH), 126.7 (CH), 129.0 (CH), 130.5, 134.7, 146.1, 158.8, 164.4 (C O2Me).MS (FAB+): m/z= 334.1 (M + H)+, calcd 334.0.2-Amino-3-(4-fluorophenylthio)-6-(methoxycarbonyl)imidazo[1,2-a]pyridine(14c): isolated in 55% yield after column chromatography. 1H NMR (200 MHz, CDCl3): d= 3.84 (s, 3H, CO2Me), 4.53 (bs, 2H, N H2), 6.82–6.96 (m, 4H, Ar H), 7.31 (dd, J58= 0.9 Hz, J78= 9.2 Hz, H8), 7.74 (dd, J57= 1.7 Hz, J78= 9.2 Hz, H7), 8.71 (dd, J57= 1.7 Hz, J58= 0.9 Hz, H5).13C NMR (50 MHz, CDCl3): d= 52.3 (CO2Me), 90.6, 113.9 (CH), 115.9, 116.4 (d, CH, J CF= 22.3 Hz), 126.0 (CH), 126.9 (CH), 127.4。