水介质中水溶性钌烯烃置换催化剂的异质化去除与寄主交互作用
概要
开发了一种可移动的水溶性n-杂环卡宾 (NHC) 配体在水介质中的宿主-来宾相互作用。我们在水中和二氯甲烷中表现出了代表性的烯烃置换反应。通过主-客交互或萃取, 在反应后, 残余钌 (钌) 催化剂的低至 0.14 ppm。
Abstract
研制了一种高效的过渡金属催化剂脱除方法。水溶性催化剂中含有一种新设计的 NHC 配体, 可通过宿主-来宾相互作用来去除催化剂。新的 NHC 配体拥有一个金刚烷基 (客) 栓线性乙烯乙二醇单位为疏水性包裹入β-环糊精 (β CD) 宿主化合物的腔内。将新型 NHC 配体应用于钌基烯烃置换催化剂中。钌催化剂在水介质中具有代表性环合置换 (RCM) 和环开置换聚合 (嬉戏) 反应的优良活性, 以及有机溶剂, CH2氯2。反应完成后, 用不溶性二氧化硅接枝β-镉 (寄主) 之间的主-客相互作用, 从水溶液中去除 99% (53 ppm) 的水溶性钌渣, 并对其进行简单过滤。金刚烷基基团 (客人) 在催化剂上。在有机溶剂中, 通过将粗反应混合物划分为二乙基醚与水之间的混合反应, 新的钌基催化剂也表现出高的去除效率。这样, 催化剂只停留在水层中。在有机层中, 在二烯丙基化合物的 RCM 反应中, 残余钌含量仅为 0.14 ppm。
Introduction
从产品中去除同类有机金属催化是现代化学1、2中的一个重要问题。残留催化剂不仅是其重金属元素的毒性问题, 而且是产物从其潜在反应性中产生的不期望的转化。均质催化剂具有活性高、反应速度快、chemoselectivity3等优点, 但其从产品中去除的难度要远远大于非均匀催化剂, 只需过滤或迁.均质和异质催化剂的优点,即均相反应和异质去除, 是高活性、易移动有机金属催化剂的重要概念。图 1说明了同质反应的工作原理, 并通过宿客相互作用的异构去除催化剂。
宿客化学是在超分子化学4、5、6、7、8中, 宿主分子与 noncovalent 分子识别之间的结合。环糊精 (CDs), 循环寡糖, 是代表性的宿主分子9,10,11,12, 它们已经应用于广泛的科学领域, 如高分子科学13,14、催化15、16、生物医学应用6、10和分析化学17。一个客人分子, adamatane, 强烈绑定到β CD (宿主, 7-元循环糖类) 的疏水腔与高协会常数, Ka (日志ka = 5.04)18。这种超分子结合亲和性足够强, 可以从含固体β镉的水反应溶液中去除残留的催化剂复合物。
在许多符合主客搬迁条件的催化剂中, 钌烯烃置换催化剂由于实用性强, 对空气和湿气的稳定性高而受到研究。烯烃置换反应是合成化学中的重要工具, 在过渡金属催化剂19、20、21、22的存在下形成碳-碳双键。稳定钌烯烃置换催化剂的研制触发置换作为合成化学的主要领域 (如RCM 和十字置换 (CM)) 以及高分子科学 (例如, 嬉戏和无环二烯置换 (ADMET))。特别是, RCM 综合了大环化合物和中型环, 这是很难建设23。
尽管钌催化烯烃置换合成实用, 但从所需产品中完全去除所用的钌催化剂是许多实际应用的一个重大挑战24。例如, 在硅胶柱层析法25中, 在环合置换产品中观察到了钌渣的 1912 ppm。残留钌可能会引起诸如烯烃异构化、分解、着色和药物毒性等问题26。国际协调会议 (ICH) 发表了药物残留金属试剂指南。药剂产品中的最大允许钌含量为 10 ppm27。出于这些原因, 试图从产品解决方案28、29、30、31、32、33中去除汝渣。并研究了可摘钌催化剂在反应后无特殊处理的情况下进行提纯。在各种纯化方法中, 对催化剂配体改性进行了改进, 提高了硅胶过滤和液体萃取的效率。例如, 在苄叉34或 NHC 配体35、36的主干上引入离子标记, 可以实现高效硅胶过滤。NHC 配体上的催化剂轴承聚乙二醇37或离子标记35可提高钌催化剂的水萃取效率。
近年来, 我们报道了一种高水溶性钌烯烃置换催化剂, 它不仅表现出高反应性, 而且具有较高的催化剂去除率。此外, 置换和催化剂的去除发生在水和二氯甲烷34,35,36,37。新的催化剂的主要特点是新的 NHC 金刚烷基栓寡核苷酸 (乙二醇)。寡核苷酸 (乙二醇) 提供了整个催化剂复合物的高水溶性。此外, 寡核苷酸 (乙二醇) 拥有金刚烷基端组, 可用于与外部β CD 的宿客互动。
在这里, 我们描述了催化剂合成, 置换反应, 以及在水和二氯甲烷脱除催化剂的协议。
Protocol
Representative Results
Discussion
本文介绍了可拆卸均质钌烯烃置换催化剂的合成及其从水和有机溶液中的脱除。同质催化剂相比, 均相催化具有反应性高、反应速度快等优点;然而, 从产品中去除所用的催化剂比异质催化剂3的难度更大。合成催化剂的主要特点是 NHC 配体, 它具有金刚烷基拴系水溶性寡核苷酸 (乙二醇)。所提出的催化剂在水溶液和有机溶液中均表现出均质反应, 并利用主-客互动<sup class="xref…
開示
The authors have nothing to disclose.
Acknowledgements
这项工作得到佛罗里达州立大学能源和材料招聘倡议和 FSU 化学和生物医学工程部的支持。
Materials
| Hoveyda-Grubbs Catalyst 1st Generation | Sigma-Aldrich | 577944 | Air sensitivie. Light sensitivie. |
| Diethyl diallylmalonate | Sigma-Aldrich | 283479 | |
| Ethyl vinyl ether | Sigma-Aldrich | 422177 | Air sensitive. |
| Aluminum oxide | Sigma-Aldrich | 06300 | Activated, neutral, Brockmann Activity I |
| Potassium bis(trimethylsilyl)amide solution (0.5 M in toluene) | Sigma-Aldrich | 277304 | Moisture sensitive. |
| Etyhl acetate | VWR | BDH1123 | Flammable liquid. |
| Methanol | VWR | BDH1135 | Flammable liquid. Toxic. |
| Deuterium Oxide 99.8%D | TCI | W0002 | |
| Methylene Chloride-D2 (D, 99.8%) | Cambridge Isotope Laboratories, Inc. | DLM-23 | Flammable liquid. Toxic. |
| Activated carbon | Sigma-Aldrich | 242276 | |
| Magnesium sulfate | EMD Millipore | MX0075 | |
| Ethyl ether | EMD Millipore | EX0190 | Flammable liquid. |
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