【作者】 杨敏；

【导师】 谢如刚；

【作者基本信息】 四川大学 ， 有机化学， 2006， 博士

【摘要】 在有机化学中烯酮、烯二酮、二烯酮等占有重要的地位，它们是许多天然产物的基本单元，是生产药品、香料、食品添加剂、农业化学品、功能材料等的原料和中间体，也是多种重要化合物，如手性醇、酯和醚的前体，可以广泛作为有机合成中的构建单元以形成复杂分子。在获取烯酮的众多方法中，烯烃及其衍生物的烯丙位氧化是最主要的方法之一。目前，已经建立的烯丙位氧化方法有：各种铬试剂或二氧化硒作氧化剂的方法；基于铬的分子筛或催化量三氧化铬结合叔丁基过氧化氢的方法；各种硒酸试剂结合碘氧苯的方法；最近报道的己内酰胺二铑配体和叔丁基过氧化氢催化氧化方法；过渡金属催化结合叔丁基过氧化氢的方法。这些方法有的表现出较好的收率，但是仍然存在一些问题，例如铬试剂和二氧化硒的危害性、复杂配体的制备、昂贵的催化剂、较长的反应时间、催化剂的回收、产品的分离、无水叔丁基过氧化氢使用安全问题、有机溶剂的环境负担等等。这些问题的改善和解决还有待进一步的探索工作。因此，进一步研发简单、有效、环境友好的方法一直是化学界关注的最具挑战性的课题。α-紫罗兰酮、β-紫罗兰酮及其醚、酯类衍生物是天然芳香植物如：桂花、紫罗兰、西番莲、茶叶、烟草等的重要香味组分，广泛地应用于精细化工，制药以及香料工业中。在紫罗兰酮及其衍生物的烯丙位上引入羰基活性基团，不但可以进一步构建更复杂的分子，而且更为重要的是形成类紫罗兰酮二烯酮后，香气变得珍稀独特，用于水果、烟草、鲜花香精或添加剂中，增香矫味，具有很高的应用价值。据我们所知，用于类紫罗兰酮二烯的烯丙位氧化的方法非常有限，都是使用化学计量的三氧化铬或铬酸叔丁酯作氧化剂。最近有报道用催化量的三氧化铬和叔丁基过氧化氢氧化二氢-β-紫罗兰酮，但是来自三氧化铬的危害仍然存在。离子液作为环境友好和可以回收的反应介质和催化剂，近年来受到了极大的关注。许多有机反应在离子液中得以实现，取得了比有机溶剂更好或相当的结果。醇的氧化，烯烃的环氧化在离子液中都取得了好结果。但是至今未见烯丙位氧化在离子液中进行的报道。结合以上三个领域的研究现状，进一步研发新的、有效的、环境友好的、针对精细化学品生产中应用底物的烯丙位氧化的新方法，不但是有机化学中的重要课题，也将成为精细化学品生产中有创新性和重大应用价值的成果。我们首先在咪唑鎓离子液中建立了一种简便有效的、选择性好的烯丙位氧化类紫罗兰酮二烯合成双烯酮的方法。在20 mol％CuCl₂·2H₂O存在下，以简单咪唑鎓六氟磷酸盐或四氟硼酸盐离子液为反应介质，3～5 equiv的70％叔丁基过氧化氢水溶液，成功氧化紫罗兰酮及其酯醚类衍生物，以45％～71％的产率获得相应的烯酮。进一步探索成本相对低廉的离子液作为反应介质，选用N-丁基吡啶鎓六氟磷酸盐或四氟硼酸盐离子液，在类似条件下氧化紫罗兰酮及其酯醚类衍生物，也以47％～72％的产率获得相应的烯酮。这是目前这类化合物烯丙位氧化合成烯酮最好的结果。在咪唑鎓和吡啶鎓离子液中，仅以简单铜盐为催化剂和叔丁基过氧化氢为氧化剂，不加入任何其他的碱或配体的类紫罗兰酮二烯的烯丙位氧化，具有反应时间短、使用无毒价廉的催化剂、氧化剂用量小、产率好、反应介质可回收等优点。迄今未见文献报道。采用透射电镜技术（TEM）首次展示了形成和稳定在咪唑鎓或吡啶鎓离子液中的Cu（Ⅱ）纳米粒子（20～300nm，10～20 nm）的催化形态。这对于理解新的催化系统CuCl₂·2H₂O-t-BuOOH-[bmim]X或[bpy]X，以及过渡金属在咪唑鎓或吡啶鎓离子液中进行氧化反应，催化剂是在分子水平还是在纳米水平上发挥作用，提供了依据。的产率获得相应的烯酮。以简单钙盐或镁盐为催化剂和叔丁基过氧化氢为氧化剂，不加入任何其他的碱或配体的类紫罗兰酮二烯的烯丙位氧化，迄今未见文献报道。基于实验结果首次提出了钙镁离子催化的，非氧化还原型的烯丙位氧化类紫罗兰酮二烯的反应机理。新的催化系统，具有反应时间短、使用无毒价廉的催化剂、直接用70％叔丁基过氧化氢水溶液代替无水叔丁基过氧化氢，氧化剂用量小、且更安全、产率好等优点。进一步探索钙镁离子的催化作用，将开辟钙镁离子催化反应的新领域。巨豆三烯酮不但是烟叶中重要的香味化合物，对烟叶的香气吃味质量有重要作用，而且也是许多天然香料的香味成分，有很高的价值，广泛地应用于食品、香水、化妆品和烟草等行业。之前所报道的合成方法存在着步骤多、产率低，反应条件苛刻等限制，我们在成功地解决了合成中产率最低的烯丙位氧化步骤后，建立了一条新的由紫罗兰酮合成巨豆三烯酮的路线，这条新的合成路线只经过氧化—还原—消去重排三步反应就合成了巨豆三烯酮，总产率＞50％。这是迄今为止由紫罗兰酮合成巨豆三烯酮最简单，产率最高的方法，不使用复杂的配体，不要求无水无氧操作和很低的反应温度等，这一新方法将具有很好的工业推广价值。上述创新性的应用基础研究成果，可为我国进行自主知识产权的烟草香味化合物的合成研究奠定基础。本研究成果还可以推广应用到香料、药物、精细化学品等行业。更多还原

【Abstract】 Enones, endiones, dienones are of importance in organic chemistry because which are basic blocks of natural products and synthesis chemistry, materials and intermediates in synthesis of pharmaceutical, flavor and fragrance, agricultural chemicals, functional material, and importance precursors to many chiral organic compounds e.g chiral alcohols, ethers and esters. Among methods of producing enones, the allylic oxidation is one of main protocols.To date, the methods established for allylic oxidation mainly refer to the traditional methods based on chromium compounds, the improved systems of chromium-based molecular sieve and chromium trioxide with tert-butyl hydroperoxide, the procedures of selenium dioxide and perfluorooctylseleninic acid-iodoxybenzene and the approach of dirhodium（Ⅱ） caprolactamate catalyzed by with tert-butyl hydroperoxide. Transition metal （e.g. Cu, Co, Pd, etc） catalyzed processes in conjunction with a terminal oxidant offer a promising alternatives. Many of these systems are useful synthetically, but several issues remain, including un-available and expensive catalyst, long reaction time, catalyst/product separation, catalyst reuse, the environmental burden of volatile organic solvents, and safety concerns of using anhydrous tert-butyl hydroperoxide. Therefore, further investigation is high desirable. The development of simple, efficient and environmentally friendly method is a challenge for chemistry communitesIonones and their derivatives are flavor components of many natural essential oil such as osmanthus, passion fruit, tea, and tobacco. They are appreciated synthetic building blocks due to their remarkable contributions in the synthesis of many medicine, biological active and flavor and fragrance compounds.4 Especially, the introduction of an active carbonyl group in their cyclohexene allylic C-H bond can not only construct more complex molecules, but also yield valued-added products, utilized to the essence of fruit, tobacco, flower and food additives. However, the direct synthesis of dienones by the allylic oxidation of ionones and their derivatives have required either stoichiometric chromium reagent （CrO₃ or （t-BuO）₂CrO₂）. Recently, it is reported that using catalytic amount chromium trioxide with tert-butyl hydroperoxide,β-dihydro-ionone was converted to 4-oxo-β-dihydro-ionone. Although the latter avoided the use of stoichiometric reagents, the hazard from chromium trioxide remains.Ionic liquids as environmentally benign and recoverable solvents have received considerable attentions. Various reactions can carry out in them, and the equal or better outcome have been obtained. The oxidation of alcohols, the epoxidation of alkenes have well run in ionic liquid. However, to the best of our knowledge, no report has been presented involving the allylic oxidation of alkenes in ionic liquid, particularly ionone-like dienes.Based on the background, the development of new, efficient, environmentally friendly protocol of allylic oxidation would be not only an important subject in organic chemistry, but also become innovative and practical findings.We originally established a simple, efficient, selective method for the allylic oxidation of ionone-like dienes in imidazolium ionic liquids. In the presence of 20 mol% CuCl₂·2H₂O, ionone and their derivates were converted to corresponding eneones and the yields 45%～71% were afforded using [bmim]BF4 or [bmim]PF₆ as reaction medium and 3-5 equiv of aqueous 70% TBHP.We further utilized more low cost ionic liquids as reaction medium, and in [bpy]BF₄ or [bpy]PF₆ the enones of ionone and their derivates were provided with 47%～72% of yield under the similar conditions. This is the best results of synthesis of the enones of ionone and their derivates. Few reports were presented on the allylic oxidation in imidazolium or pyridinium ionic liquids, and without ligand and base the method of allylic oxidation exhibited many advantages including short reaction time, the use of nontoxic catalyst, low amount of TBHP, the good yields of product, and the facile recovery and recycling of reaction media.We firstly disclosed the size and shape of Cu （Ⅱ） nanoparticales of formation and stabilization in imidazolium or pyridinium ionic liquids by TEM, which give us insight into the CuCl₂·2H₂O-t-BuOOH-[bmim]X or [bpy]X catalytic system.,We also established a new strategy of allylic oxidation of ionone-like based on CaCl₂ or MgCl₂ catalyst. In the presence of 20 mol～30 mol% of CaCl₂ or MgCl2·6H₂O ionone and their derivates can be oxidized corresponding dienones using acetonitrile as solvent with 3-5equiv of aqueous 70% TBHP at 80℃for 4 h, and 42%～456% yields were achieved. To date, no report involved the allylic oxidation of ionone-like dienes with the catalyst of simple calcium or magnesium salt. More important, we proposed a mechanism to account for the non-redox allylic oxidation.The advantage of the new catalytic system （CaCl₂ or MgCl₂·6H₂O-TBHP） are numerous: the utilization of Ca²⁺or Mg²⁺, pretty cheap and nontoxic as well as essential for life, and low amount and direct application of aqueous 70% solution of TBHP, mild reaction conditions, relative short reaction time, and better yield of product. It is believed that the deeply explore the catalytic function of Ca²⁺ or Mg²⁺ would open new areas catalysis by Ca²⁺or Mg²⁺.Megastigmatrienone are known as key tobacco flavoring components and can improve smoking characteristics. Moreover, they serve as the composition of natural essential oil with high value and are frequently utilized to food, perfume, cosmetic and tobacco. The previous methods of synthesizing megastigmatrienone remain many problems, such as long synthetic route, low yield, and harsh reaction conditions. We successively improved the process of the allylic oxidation with low yield, and then develop a new synthetic route of megastigmatrienone using a-ionone as starting material, which are composed of oxidation, reduction and elimination and with good overall yield（＞50%）. This is the simplest and efficient method in the synthesis of megastigmatrienone. No requirement of moisture-free, air-free and very low temperature make the new approach more practical in industry scale.These innovation outcome would support the research of self-dependant synthesis of tobacco flavor component and be widely used in fine chemistry, pharmaceutical and flavor and fragrance industry.更多还原