- Title
- The synthesis of anastrazole intermediates using continuous flow systems
- Creator
- Tanyi, Sam Tambi
- Subject
- Port Elizabeth (South Africa)
- Subject
- Eastern Cape (South Africa)
- Subject
- South Africa
- Date Issued
- 2021-12
- Date
- 2021-12
- Type
- Master's theses
- Type
- text
- Identifier
- http://hdl.handle.net/10948/54116
- Identifier
- vital:46304
- Description
- In this study, the continuous flow synthesis of anastrozole intermediates were investigated using mesitylene as starting material. Anastrozole is an important drug used for the treatment of breast cancer. In the first step, mesitylene was brominated using N-bromosuccinimide to obtain 3,5-bis(bromomethyl)toluene. Selectivity became an issue due to the formation of two by-products; namely 1,3,5-tris(bromomethyl) benzene (the tribrominated by-product) and 1-(bromomethyl)-3,5-dimethylbenzene (the monobrominated by-product). Since the reaction parameters can be more precisely controlled in flow chemistry systems, we were able to optimize the formation the desired product 3,5-bis(bromomethyl)toluene. The reaction was initially optimized ina 15μLChemtrix glass micro reactor resulting in 100%conversion with 95%selectivity towards the desired product 3,5-bis(bromomethyl)toluenein 15 seconds, with a throughput of 0.006 g/h. The reaction was then scaled up in a 1.7 mLLTF reactor, equally yielding 100%conversion with 95%selectivityin 4minutes, with a throughput of2.01g/h. The bromination of mesitylene was also attempted in a homemade photochemical reactor consisting of a 3.02 polytetrafluoroethylene coil reactor and BLE-6T365 UV lamp. In this photochemical reactor, although 100%conversionwas again obtained only75%selectivity was achieved in 20minutes, with a throughput of 0.025g/h. This drop in selectivity was attributed to poorer mixing in the larger polytetrafluoroethylene coil reactor and possibly insufficient light penetration. The next step, involving the cyanation of 3,5-bis(bromomethyl)toluene to obtain 2,2'-(5-methyl-1,3-phenylene) diacetonitrilegave 100%conversion in 1 minute at 190 °C in a 1.7 mLLTFreactor, with a throughput of 5.2g/h. The subsequent methylation of 3,5-bis(cyanomethyl)toluene to obtain3,5-bis(1-cyano-1-methylethyl) toluene was investigated using a1mLpolytetrafluoroethylenecoil reactor, ultimatelyachieving99%conversionat40 °Cin 8minutes, with a throughput of 0.045g/h. Next, the bromination of3,5-bis(1-cyano-1-methylethyl)toluene using N-bromosuccinimideto yield 2,2'-(5-bromomethyl-1,3-phenylene)di(2-methyl propionitrile) gave 100%conversion at 120 °C in 4 minutes, with a throughput of 0.35g/h. Lastly, the multistep synthesis of 3,5-bis(cyanomethyl)toluene was done in two integrated 1.7 mLLTF reactors, using the predetermined optimum conditions to achieve 94%conversion towards 3,5-bis(cyanomethyl)toluene with a total r
- Description
- Thesis (MSc) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2021
- Format
- computer
- Format
- online resource
- Format
- application/pdf
- Format
- 1 online resource (144 pages)
- Format
- Publisher
- Nelson Mandela University
- Publisher
- Faculty of Science
- Language
- English
- Rights
- Nelson Mandela University
- Rights
- All Rights Reserved
- Rights
- Open Access
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| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Tanyi, S.pdf | 2 MB | Adobe Acrobat PDF | View Details Download |