Using Solvent-Free Mechanochemistry to Improve the Selectivity of Traditional Solution Based Chemical Reactions

利用无溶剂机械化学提高传统溶液化学反应的选择性

• 批准号: 1900097
• 负责人: James Mack II
• 金额: $ 48.5万
• 依托单位: University of Cincinnati Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1900097&HistoricalAwards=false
• 关键词: Using; Solvent; Free; Mechanochemistry; Improve

In this project, funded by the Chemical Synthesis Program of the Chemistry Division, Professor James Mack II of the Department of Chemistry at the University of Cincinnati is developing environmentally benign ways to conduct organic synthesis. Solvents, typically volatile organic compounds, represent roughly 85% of the total mass used in pharmaceutical manufacturing. As a result, many companies have developed guidelines to ensure the utilization of environmentally benign solvents in the synthesis of drugs. In addition to the amount of waste produced using solvents, solvents themselves are costly to acquire. The goal of this project is to understand how to conduct chemical reactions in the absence of such solvents in order to significantly reduce the total amount of harmful waste produced during a chemical reaction. The method of mechanochemistry used in this project can be performed by scientists at various levels, making it a useful tool to introduce the concepts of green chemistry to a broad audience. Professor Mack II has an excellent history of mentoring students from underrepresented minority groups and is continuously reaching out to the community and the students with the support of this grant. In addition to environmental concerns, there are other significant benefits of performing solvent free mechanochemistry. In solution, the rate and selectivity of a reaction are both tied to temperature; however, under solvent-free mechanochemical conditions the rate and temperature can be independent of each another. In this project, increased selectivity of chemical reactions will be performed through unique control over the temperature, mixing, and redox potential of reagents. In solution, there is limited control on the mixing rate of reagents which can have a significant effect on the overall kinetics and selectivity of a chemical reaction. This project seeks to understand how greater control over mixing in a solvent-free system can affect the kinetics and selectivity of various chemical reactions. Using examples of enantioselective versions of the Morita-Baylis Hillman reactions, a three-component coupling reaction and a Diels-Alder reaction, new methods of selectivity are expected to be observed under mechanochemical conditions that are not available to synthetic chemists in solution.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学部化学合成计划资助的该项目中，辛辛那提大学化学系的詹姆斯·麦克二世教授正在开发环境良性的进行有机合成的方式。 溶剂（通常为挥发性的有机化合物）约占药物制造中使用的总质量的85％。 结果，许多公司已经制定了指南，以确保在综合药物中利用环境良性溶剂。 除了使用溶剂产生的废物数量之外，溶剂本身还要昂贵。 该项目的目的是了解如何在没有此类溶剂的情况下进行化学反应，以显着减少化学反应过程中产生的有害废物的总数。 该项目中使用的机械化学方法可以由科学家在各个层面上执行，这使其成为向广泛受众介绍绿色化学概念的有用工具。麦克二世教授拥有良好的历史，指导来自代表性不足的少数群体的学生，并在这笔赠款的支持下不断与社区和学生接触。除了环境问题外，执行溶剂自由机械化学还有其他重大好处。 在溶液中，反应的速率和选择性均与温度相关。但是，在无溶剂机械化学条件下，速率和温度可以彼此独立。 在该项目中，化学反应的选择性提高将通过对试剂的温度，混合和氧化还原电位的独特控制来执行。 在溶液中，对试剂的混合速率的控制有限，这可能会对化学反应的整体动力学和选择性产生重大影响。 该项目旨在了解无溶剂系统中对混合的控制如何影响各种化学反应的动力学和选择性。 使用Morita-Baylis Hillman反应的对映选择性版本的示例，三组分耦合反应和Diels-Alder反应，预计将在机械化学条件下观察到新的选择性方法，这些方法在机械化学条件下无法获得合成化学家在解决方案中无法获得的，这些奖项反映了NSF的法定任务和良好的依据。 标准。

项目成果

Radical Reduction of Alkyl and Aryl Halides under Mechanochemical Conditions

机械化学条件下烷基和芳基卤化物的自由基还原

• DOI: 10.1021/acssuschemeng.3c01544
• 发表时间: 2023
• 期刊: ACS Sustainable Chemistry & Engineering
• 影响因子: 8.4
• 作者: Silva, W. Rohesh;Hellmann, Jaina E.;Mack, James
• 通讯作者: Mack, James

Developing benign syntheses using ion pairs via solvent-free mechanochemistry

• DOI: 10.1039/d0gc01116a
• 发表时间: 2020-06-07
• 期刊: GREEN CHEMISTRY
• 影响因子: 9.8
• 作者: Ortiz-Trankina, Lianna N.;Crain, Jazmine;Mack, James
• 通讯作者: Mack, James

Milligram-scale, temperature-controlled ball milling to provide an informed basis for scale-up to reactive extrusion

• DOI: 10.1039/d1gc02174e
• 发表时间: 2021-09-30
• 期刊: GREEN CHEMISTRY
• 影响因子: 9.8
• 作者: Andersen, Joel;Starbuck, Hunter;Mack, James
• 通讯作者: Mack, James

Investigation of Mechanochemical Sonogashira Couplings─From Batch Solution to Continuous Reactive Extrusion through Ball-Milling Optimization

机械化学 Sonogashira 联轴器的研究——通过球磨优化从间歇解决方案到连续反应挤出

• DOI: 10.1021/acs.oprd.3c00200
• 发表时间: 2023
• 期刊: Organic Process Research & Development
• 影响因子: 3.4
• 作者: Hastings, Riley H.;Mokhtar, Mennatullah M.;Ruggles, Alexander;Schmidt, Constanze;Bourdeau, David;Haibach, Michael C.;Geneste, Hervé;Mack, James;Co, Sarah S.;Speight, Isaiah R.
• 通讯作者: Speight, Isaiah R.