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.

在这个由化学系化学合成项目资助的项目中，辛辛那提大学化学系的詹姆斯·麦克二世教授正在开发对环境无害的方法来进行有机合成。溶剂，通常是挥发性有机化合物，约占药品制造中使用的总质量的85%。因此，许多公司制定了指导方针，以确保在药物合成中使用无害环境的溶剂。除了使用溶剂产生的废物量外，溶剂本身的获取成本也很高。该项目的目标是了解如何在没有这种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总量。本项目使用的机械化学方法可以由不同层次的科学家进行，使其成为向广大受众介绍绿色化学概念的有用工具。麦克二世教授在指导少数族裔学生方面有着出色的历史，并在这项资助的支持下不断向社区和学生伸出援手。除了环境问题外，进行无溶剂机械化学还有其他显著的好处。在溶液中，反应的速率和选择性都与温度有关；然而，在无溶剂的机械化学条件下，速率和温度可以相互独立。在这个项目中，将通过对试剂的温度、混合和氧化还原电位的独特控制来提高化学反应的选择性。在溶液中，对试剂混合速率的控制是有限的，而混合速率对化学反应的总体动力学和选择性有重要影响。该项目旨在了解在无溶剂系统中对混合的更大控制如何影响各种化学反应的动力学和选择性。利用Morita-Baylis Hillman反应、三组分偶联反应和Diels-Alder反应的对映选择性，有望在机械化学条件下观察到新的选择性方法，这是合成化学家在溶液中无法获得的。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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

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.

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