Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide Using Flow Chemistry
© 2018 American Chemical Society. The kinetics of sequential addition of a distinct Grignard species onto a lactone is studied by flow chemistry. The experimental data are shown to be consistent with a kinetic model based on four reaction steps, reaction of ester to magnesium hemiacetal, rearrangeme...
| Main Authors: | , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society (ACS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/135019 |
| _version_ | 1826212555525193728 |
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| author | Pedersen, Michael J Born, Stephen Neuenschwander, Ulrich Skovby, Tommy Mealy, Michael J Kiil, Søren Dam-Johansen, Kim Jensen, Klavs F |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Pedersen, Michael J Born, Stephen Neuenschwander, Ulrich Skovby, Tommy Mealy, Michael J Kiil, Søren Dam-Johansen, Kim Jensen, Klavs F |
| author_sort | Pedersen, Michael J |
| collection | MIT |
| description | © 2018 American Chemical Society. The kinetics of sequential addition of a distinct Grignard species onto a lactone is studied by flow chemistry. The experimental data are shown to be consistent with a kinetic model based on four reaction steps, reaction of ester to magnesium hemiacetal, rearrangement to ketone (forward and backward), and reaction of ketone to tertiary alcohol upon quenching. The experimental derived reaction mechanism is supported by ab initio molecular computations, and the predicted activation energy is in good agreement with the experimental observations. The Grignard reaction follows a substrate-independent, reductive [2 + 2] cycloaddition of the Meisenheimer/Casper type. Moreover, the rearrangement equilibrium between magnesium hemiacetal and ketone is characterized and found to be feasible. Monoaddition of the ester carbonyl group is demonstrated for fluorophenylmagnesium bromide but at reaction conditions at -40 °C with several hours of residence time. Working under cryogenic temperature conditions is essential to realizing monoaddition of the ester carbonyl group with Grignard reagents. |
| first_indexed | 2024-09-23T15:25:07Z |
| format | Article |
| id | mit-1721.1/135019 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:25:07Z |
| publishDate | 2021 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1350192023-02-22T17:45:03Z Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide Using Flow Chemistry Pedersen, Michael J Born, Stephen Neuenschwander, Ulrich Skovby, Tommy Mealy, Michael J Kiil, Søren Dam-Johansen, Kim Jensen, Klavs F Massachusetts Institute of Technology. Department of Chemical Engineering © 2018 American Chemical Society. The kinetics of sequential addition of a distinct Grignard species onto a lactone is studied by flow chemistry. The experimental data are shown to be consistent with a kinetic model based on four reaction steps, reaction of ester to magnesium hemiacetal, rearrangement to ketone (forward and backward), and reaction of ketone to tertiary alcohol upon quenching. The experimental derived reaction mechanism is supported by ab initio molecular computations, and the predicted activation energy is in good agreement with the experimental observations. The Grignard reaction follows a substrate-independent, reductive [2 + 2] cycloaddition of the Meisenheimer/Casper type. Moreover, the rearrangement equilibrium between magnesium hemiacetal and ketone is characterized and found to be feasible. Monoaddition of the ester carbonyl group is demonstrated for fluorophenylmagnesium bromide but at reaction conditions at -40 °C with several hours of residence time. Working under cryogenic temperature conditions is essential to realizing monoaddition of the ester carbonyl group with Grignard reagents. 2021-10-27T20:10:21Z 2021-10-27T20:10:21Z 2018 2019-08-22T12:40:37Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135019 en 10.1021/ACS.IECR.8B00564 Industrial and Engineering Chemistry Research Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) Other repository |
| spellingShingle | Pedersen, Michael J Born, Stephen Neuenschwander, Ulrich Skovby, Tommy Mealy, Michael J Kiil, Søren Dam-Johansen, Kim Jensen, Klavs F Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide Using Flow Chemistry |
| title | Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide Using Flow Chemistry |
| title_full | Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide Using Flow Chemistry |
| title_fullStr | Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide Using Flow Chemistry |
| title_full_unstemmed | Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide Using Flow Chemistry |
| title_short | Optimization of Grignard Addition to Esters: Kinetic and Mechanistic Study of Model Phthalide Using Flow Chemistry |
| title_sort | optimization of grignard addition to esters kinetic and mechanistic study of model phthalide using flow chemistry |
| url | https://hdl.handle.net/1721.1/135019 |
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