Synthesis of drug intermediates in carbon dioxide
The application of supercritical C0₂(scC0₂) as a solvent for the synthesis of fine and bulk chemicals has been well documented; however its application as a solvent for the synthesis of pharmaceuticals is yet to be exploited fully. To address this issue, two synthetically important reactions have be...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
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2007
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| Online Access: | https://eprints.nottingham.ac.uk/11912/ |
| _version_ | 1848791387782250496 |
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| author | Clark, Peter David |
| author_facet | Clark, Peter David |
| author_sort | Clark, Peter David |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The application of supercritical C0₂(scC0₂) as a solvent for the synthesis of fine and bulk chemicals has been well documented; however its application as a solvent for the synthesis of pharmaceuticals is yet to be exploited fully. To address this issue, two synthetically important reactions have been investigated in scC0₂; chemoselective N-debenzylation and diastereoselective hydrogenation.
Chapter 3 details the study of catalytic N-debenzylation in the presence of sensitive functional groups (COMe and Cl). It has been shown that selective N-debenzylation in the presence of a carbonyl (COMe) is difficult to achieve due to the high operating temperatures that are required to facilitate continuous flow debenzylation. N-debenzylation in the presence of chloro- substituents was also investigated. Dechlorination can be a major problem during this reaction however several different strategies were developed to suppress dechlorination including:
(i) the correct selection of catalyst support; (ii) selective poisoning of a Pd catalyst;
(iii) the addition of acids, such as H₂S0₄ to the reactant stream; (iv) the use of an aprotic co-solvent, such as THF.
Chapter 4 covers progress made on the diastereoselective hydrogenation of the pharmaceutical intermediate, rac-sertraline imine. It has been shown that the hydrogenation reaction can be performed with excellent levels of chemo- and diastereoselectivity (cis:trans ratio of 97:3, 0.7 % by-product formation) by performing the reaction as a continuous flow process in the presence of scC0₂
All details of the apparatus, experimental and synthetic procedures are reported in Chapter 2. |
| first_indexed | 2025-11-14T18:27:42Z |
| format | Thesis (University of Nottingham only) |
| id | nottingham-11912 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T18:27:42Z |
| publishDate | 2007 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-119122025-02-28T11:16:18Z https://eprints.nottingham.ac.uk/11912/ Synthesis of drug intermediates in carbon dioxide Clark, Peter David The application of supercritical C0₂(scC0₂) as a solvent for the synthesis of fine and bulk chemicals has been well documented; however its application as a solvent for the synthesis of pharmaceuticals is yet to be exploited fully. To address this issue, two synthetically important reactions have been investigated in scC0₂; chemoselective N-debenzylation and diastereoselective hydrogenation. Chapter 3 details the study of catalytic N-debenzylation in the presence of sensitive functional groups (COMe and Cl). It has been shown that selective N-debenzylation in the presence of a carbonyl (COMe) is difficult to achieve due to the high operating temperatures that are required to facilitate continuous flow debenzylation. N-debenzylation in the presence of chloro- substituents was also investigated. Dechlorination can be a major problem during this reaction however several different strategies were developed to suppress dechlorination including: (i) the correct selection of catalyst support; (ii) selective poisoning of a Pd catalyst; (iii) the addition of acids, such as H₂S0₄ to the reactant stream; (iv) the use of an aprotic co-solvent, such as THF. Chapter 4 covers progress made on the diastereoselective hydrogenation of the pharmaceutical intermediate, rac-sertraline imine. It has been shown that the hydrogenation reaction can be performed with excellent levels of chemo- and diastereoselectivity (cis:trans ratio of 97:3, 0.7 % by-product formation) by performing the reaction as a continuous flow process in the presence of scC0₂ All details of the apparatus, experimental and synthetic procedures are reported in Chapter 2. 2007-07-17 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/11912/1/493129.pdf Clark, Peter David (2007) Synthesis of drug intermediates in carbon dioxide. PhD thesis, University of Nottingham. supercritical carbon dioxide drug synthesis chemoselective N-debenzylation diastereoselective hydrogenation green chemistry |
| spellingShingle | supercritical carbon dioxide drug synthesis chemoselective N-debenzylation diastereoselective hydrogenation green chemistry Clark, Peter David Synthesis of drug intermediates in carbon dioxide |
| title | Synthesis of drug intermediates in carbon dioxide |
| title_full | Synthesis of drug intermediates in carbon dioxide |
| title_fullStr | Synthesis of drug intermediates in carbon dioxide |
| title_full_unstemmed | Synthesis of drug intermediates in carbon dioxide |
| title_short | Synthesis of drug intermediates in carbon dioxide |
| title_sort | synthesis of drug intermediates in carbon dioxide |
| topic | supercritical carbon dioxide drug synthesis chemoselective N-debenzylation diastereoselective hydrogenation green chemistry |
| url | https://eprints.nottingham.ac.uk/11912/ |