Pharmaceutical and Commodity Chemical Synthesis in High-Temperature Water

高温水中的药物和日用品化学合成

• 批准号: 0625641
• 负责人: Phillip Savage
• 金额: --
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0625641&HistoricalAwards=false
• 关键词: Pharmaceutical; Commodity; Chemical; Synthesis; Temperature

ABSTRACTPI: Philip E. Savage Institution: University of MichiganProposal Number: 0625641Title: Pharmaceutical and Commodity Chemical Synthesis in High-Temperature WaterIntellectual Merit: High-temperature liquid water (HTW) is attractive as a reaction medium for organic chemical synthesis because it is inexpensive, abundant, non-toxic, renewable, environmentally benign, and has desirable chemical properties. Several different commercially relevant syntheses have been demonstrated in HTW, but many more targets of opportunity exist. Pharmaceutical reactions, for instance, are attractive targets because this sector of the chemical industry generally produces more waste per unit mass of product than any other sector. After discussions with chemists at Pfizer, the PI has decided to explore three especially attractive chemical reactions in HTW. These are a Friedel-Crafts reaction with "green" Lewis acids catalysts to synthesize tetralone, the deprotection of phenolic methyl ethers, and Suzuki coupling to make new C-C bonds. These three reactions are relevant to the manufacture of several different pharmaceutical products. In addition to the research noted above that examines new chemistries in HTW, he will also revisit syntheses that have already been demonstrated in HTW. These systems include the partial oxidation of p-xylene to make terephthalic acid (in collaboration with BP), aldol condensation, and Friedel-Crafts alkylation. The purpose here is to improve these HTW syntheses so they might become economically competitive with current processes. A limitation currently restraining implementation of HTW-based reaction technologies is that the solubilities of organic reactants are often too low to give volumetric production rates that can compete economically with existing processes. A recent advance, however, has suggested a possible route for overcoming this barrier and increasing the productivity of HTW-based processes without sacrificing the environmental benefits. This advance is the demonstration that solubility in water is not required to get fast reaction rates in water. In fact, for some reactions, heterogeneous aqueous-organic systems (vigorously stirred immiscible aqueous and organic phases) provided greatly accelerated reaction rates relative to the homogeneous conditions typically employed. To date, this effect has only been demonstrated at near ambient temperatures. The PI will explore whether it can be employed in HTW.This project will examine the partial oxidation of p-xylene to make terephthalic acid, aldol condensation, Friedel-Crafts reactions, Suzuki coupling, and ether hydrolysis. If successful, the research will lead to chemical reaction processes that are at least as productive as current ones, but are significantly more environmentally friendly. Removing the current barrier of low reactant concentrations in HTW will allow these technological advances to occur. Broad Impact:The PI will work with the UM Technology Transfer Office to make available the technological advances. The benefit of this work will extend to the chemical industry and the general public (by having less environmental risk associated with the manufacture of chemical products). The project will also provide training for a graduate student and about six undergraduate students. Additionally, the PI will continue his practice of incorporating his research results into the undergraduate and graduate classes he teaches at Michigan, so there will be benefits related to the integration of teaching and research.

摘要：Philip E.萨维奇学院：建议编号：0625641题目：高温水中的药物和日用品化学合成知识点：高温液态水（HTW）作为有机化学合成的反应介质是有吸引力的，因为它是廉价的，丰富的，无毒的，可再生的，环境友好的，并具有理想的化学性质。 几种不同的商业相关的合成已经在HTW中得到了证明，但还有更多的机会目标。 例如，药物反应是有吸引力的目标，因为化学工业的这一部门通常比任何其他部门产生更多的单位质量产品的废物。 在与辉瑞的化学家讨论后，PI决定在HTW中探索三种特别有吸引力的化学反应。 这些反应包括用“绿色”刘易斯酸催化的Friedel-Crafts反应合成四氢萘酮、酚甲基醚的脱保护和Suzuki偶联生成新的C-C键。这三种反应与几种不同药品的生产有关。 除了上面提到的研究HTW中的新化学之外，他还将重新审视已经在HTW中展示的合成。 这些系统包括对二甲苯部分氧化制对苯二甲酸（与BP合作）、羟醛缩合和Friedel-Crafts烷基化。 这里的目的是改进这些HTW合成，使它们在经济上与目前的工艺相比具有竞争力。 目前限制基于HTW的反应技术的实施的限制是有机反应物的溶解度通常太低而不能给出可以与现有方法经济竞争的体积生产速率。 然而，最近的一项进展提出了一种可能的途径，可以克服这一障碍，提高HTW工艺的生产率，而不牺牲环境效益。 这一进展表明，在水中的溶解度不需要在水中获得快速反应速率。事实上，对于某些反应，非均相水-有机体系（剧烈搅拌的不混溶的水相和有机相）相对于通常采用的均相条件提供了大大加速的反应速率。 迄今为止，这种效应仅在接近环境温度下得到证实。 PI将探索它是否可以在HTW中使用。该项目将研究对二甲苯的部分氧化，使对苯二甲酸，羟醛缩合，Friedel-Crafts反应，Suzuki偶联和醚水解。 如果成功，这项研究将导致化学反应过程，至少与目前的化学反应过程一样多产，但更环保。 消除目前HTW中低反应物浓度的障碍将使这些技术进步得以实现。 广泛的影响：PI将与UM技术转让办公室合作，提供技术进步。 这项工作的好处将扩大到化学工业和公众（通过减少与化学产品制造有关的环境风险）。 该项目还将为一名研究生和大约六名本科生提供培训。 此外，PI将继续将他的研究成果纳入他在密歇根大学任教的本科生和研究生课程的实践，因此将有与教学和研究的整合有关的好处。