1. 毕业设计（论文）的内容和要求

由于吡唑并杂环类化合物能有效控制机体炎症而日益受到关注。

而本课题所研究的3-氯-2-氰基吡嗪则是其中合成环节中不可或缺的关键化合物。

但在3-氯-2-氰基吡嗪传统合成工艺中，有着反应温度要求较高，反应时间长，副产物多，选择性差，反应物毒性强等一系列缺点，一直制约着该化合物的合成。

2. 参考文献

[1] Loidreau Y, Marchand P, Dubouilh-Benard C, et al. Synthesis and biological evaluation of N-arylbenzo[b]thieno[3,2-d]pyrimidin-4-amines and their pyrido and pyrazino analogues as Ser/Thr kinase inhibitors[J]. European Journal of Medicinal Chemistry, 2012, 58(12):171-183. [2] 匡仁云, 郭瑾, 周小春,等. 3-碘-1H-吡唑并[3,4-b]吡嗪的合成[J]. 中国医药工业杂志, 2010, 41(4):249-250. [3] Lee M R, Dominguez C. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein.[J]. Current Medicinal Chemistry, 2005, 12(25):2979. [4] Raich I, Satinsky D, Kunes J, et al. Novel Regioselective Preparation of 5-Chloropyrazine-2-Carbonitrile from Pyrazine-2-Carboxamide and Coupling Study of Substituted Phenylsulfanylpyrazine- 2-Carboxylic Acid Derivatives[J]. Current Organic Chemistry, 2005, 9(1):-. [5] 丁炬平, 余强, 张仁延. 一种3-氨基-2-氰基-6-溴吡嗪的制备方法:, CN 102675230 A[P]. 2012. [6] Holzer W, Eller G A, Datterl B, et al. Derivatives of pyrazinecarboxylic acid: 1H, 13C and 15N NMR spectroscopic investigations[J]. Magnetic Resonance in Chemistry, 2009, 47(7):617-624. [7] Johnston D B R. N-[(5-Halo-2,6-(substituted)pyrazinyl)methylene]amine antimicrobial compounds, compositions and use: US, US 4442095 A[P]. 1984. [8] Jas G, Kirschning A. Continuous Flow Techniques in Organic Synthesis[J]. Chemistry - A European Journal, 2003, 9(23):5708-23. [9] Brett A. Roberts, Christopher R. Strauss. Toward Rapid, ”Green”, Predictable Microwave-Assisted Synthesis[J]. ChemInform, 2005, 38(48):653-61. [10] Webb D, Jamison T F. Continuous flow multi-step organic synthesis[J]. Chemical Science, 2010, 1(6):675-680. [11] Wiles C, Watts P. Continuous flow reactors: a perspective[J]. Green Chemistry, 2012, 14(14):38-54. [12] Rodrigues T, Schneider P, Schneider G. Accessing New Chemical Entities through Microfluidic Systems[J]. Angew Chem Int Ed Engl, 2014, 53(23):5750-8.

3. 毕业设计（论文）进程安排

第一周~第二周：完成英文文献翻译以及开题报告 第三周~第六周：，建立有效的3-氯-2-氰基吡嗪产率及纯度的分析方法，重复传统的3-氯-2-氰基吡嗪生产工艺 第七周~第十三周：熟悉微通道反应器的操作，并对3-氯-2-氰基制备的多个控制因素进行研究 第十四周~最后：进行毕业论文的撰写以及准备答辩