- Title
- Towards the synthesis of trimethoprim using continuous flow Chemistry
- Creator
- Ngwenya, Sandiso
- Subject
- Trimethoprim
- Date Issued
- 2020
- Date
- 2020
- Type
- Thesis
- Type
- Masters
- Type
- MSc
- Identifier
- http://hdl.handle.net/10948/47475
- Identifier
- vital:39994
- Description
- The continuous flow synthesis of trimethoprim, an antibiotic, was investigated in this study from simple commercially available reagents, such as aniline and dimethylamine. The first step of the synthesis involves a highly exothermic Michael reaction, between acrylonitrile and dimethylamine; process intensification through miniaturization provides a safe and efficient method of synthesis through the use of microreactors. This is afforded by their large surface area-to-volume ratio; one of the many characteristics of continuous flow synthesis that allows for rapid heat dissipation allowing for exothermic reaction to be conducted safely at ambient or higher temperatures. This study was optimized on a Chemtrix Labtrix® Start unit using a Chemtrix reactor achieving a conversion of 99% in 12 sec residence time at 25oC. Subsequently the base catalyzed condensation of the intermediate with 3,4,5- trimethoxybenzaldehyde was investigated using Little Things Factory reactors (Channel diameter: 1.0mm). Maximum conversion (100%) was obtained at 80oC in 20 mins. Due to the poor cyclisation observed with this intermediate, according to literature findings, the 3-dimethylamino group was substituted for aniline. The optimisation for this acid catalysed substitution reaction was performed on a homemade PTFE tubing reactor (Diameter: 0.5mm) and it was found that at 120oC in 10 mins residence time a conversion of 97% was obtained. From the results obtained, an investigation into an integrated process for the condensation and substitution reaction was done using the Little Things Factory system (Channel Diameter: 1.0mm) coupled with a homemade PTFE coil reactor (Diameter: 0.5mm). This process, under optimum conditions of temperature 80oC and residence time of 30 mins, attained a conversion of 76%.
- Format
- xii, 108 leaves
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
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Collections
NMU School of BioMolecular and Chemical Sciences
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Ngwenya, S 218129661 Dissertation April 2020.pdf | 3 MB | Adobe Acrobat PDF | View Details Download |