Continuous flow synthesis of imatinib intermediates
- Authors: Rupapa, Harold Takunda
- Date: 2020
- Subjects: Flow chemistry
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/47464 , vital:39993
- Description: In this thesis, an alternative approach using continuous flow chemistry towards imatinib intermediates is described; an important drug in the treatment of acute myeloid leukemia. Various protocols that describe the multistep batch organic synthesis of imatinib are outlined. Many of the batch synthetic protocols require long reaction times in the multistep synthesis towards the various imatinib intermediates. A broad description into the cancer epidemic such as myeloid leukemia, the cost of drug manufacture and the effect that the high cost of manufacture has on the accessibility to such treatment in Africa is outlined. Use of continuous flow reactors, the exploitation of various technologies and their advantages on organic synthesis compared to batch synthesis are also described. The batch reaction conditions needed for the multistep transformation towards imatinib were adapted to a continuous flow set up. The optimization investigation shows an improvement in the conversion in the various steps. The flow synthesis of the enaminone provided a conversion of 99% when in o-xylene and the ability to use backpressure regulators assisted the investigation at high temperatures. Solution-phase flow synthesis of the guanidinium nitrate, which gave low yields in batch, also showed an improvement in conversion, where in 30 minutes a conversion of 99% was confirmed by altering the co-solvent mixture. The cycloaddition reaction of the enaminone and the guanidinium nitrate salt, achieved 90% conversion to the 2-aminopyridine core at 180 oC. The nitro group reduction was achieved in the presence of a greener catalyst, namely iron pentanedionate, in the presence of hydrazine hydrate. The effect of temperature, molar equivalence and solvent on reaction conversions could be observed in these steps. The thesis is concluded in chapter 4, with the conclusion and recommendations for future work towards a scalable continuous flow synthesis of the imatinib intermediates.
- Full Text:
- Date Issued: 2020
- Authors: Rupapa, Harold Takunda
- Date: 2020
- Subjects: Flow chemistry
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/47464 , vital:39993
- Description: In this thesis, an alternative approach using continuous flow chemistry towards imatinib intermediates is described; an important drug in the treatment of acute myeloid leukemia. Various protocols that describe the multistep batch organic synthesis of imatinib are outlined. Many of the batch synthetic protocols require long reaction times in the multistep synthesis towards the various imatinib intermediates. A broad description into the cancer epidemic such as myeloid leukemia, the cost of drug manufacture and the effect that the high cost of manufacture has on the accessibility to such treatment in Africa is outlined. Use of continuous flow reactors, the exploitation of various technologies and their advantages on organic synthesis compared to batch synthesis are also described. The batch reaction conditions needed for the multistep transformation towards imatinib were adapted to a continuous flow set up. The optimization investigation shows an improvement in the conversion in the various steps. The flow synthesis of the enaminone provided a conversion of 99% when in o-xylene and the ability to use backpressure regulators assisted the investigation at high temperatures. Solution-phase flow synthesis of the guanidinium nitrate, which gave low yields in batch, also showed an improvement in conversion, where in 30 minutes a conversion of 99% was confirmed by altering the co-solvent mixture. The cycloaddition reaction of the enaminone and the guanidinium nitrate salt, achieved 90% conversion to the 2-aminopyridine core at 180 oC. The nitro group reduction was achieved in the presence of a greener catalyst, namely iron pentanedionate, in the presence of hydrazine hydrate. The effect of temperature, molar equivalence and solvent on reaction conversions could be observed in these steps. The thesis is concluded in chapter 4, with the conclusion and recommendations for future work towards a scalable continuous flow synthesis of the imatinib intermediates.
- Full Text:
- Date Issued: 2020
Strategies to improve the representation of black women in senior levels within the South African banking industry
- Authors: Peacock, Brenda Thandiwe
- Date: 2017
- Subjects: Women bankers -- South Africa Bank management -- Women -- South Africa , Women executives -- South Africa Leadership in women -- South Africa Minorities -- Employment -- South Africa
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10948/19695 , vital:28936
- Description: The main purpose of this qualitative research study was to investigate strategies to improve the representation of black females in senior levels within the South African banking industry. This was done through investigating the challenges that black women face in their career advancement within the banking industry and the strategies which currently exist and can be implemented to improve this representation. In as much as the research is aimed at seeking strategies to improve black women representation in senior positions, it also seeks to understand the barriers experienced by black women in different levels within the industry as these levels serve as a pipeline for senior management. This problem was addressed through answering the research objectives. The research objectives were achieved through conducting a literature review to explore the existing research topic and conducting an empirical study. Empirical evidence was obtained through conducting semi-structured interviews with seven black women who are currently working in the banking sector. Semi-structured interviews were used due to the target population being specific to black women as well as the need to acquire in-depth knowledge from black women of their experiences in climbing the corporate ladder in the sector. The key findings of the research found that the participant’s perception was that black women were at the bottom, that black women were displaying behaviours that were inhibiting their progress to senior positions. The study also found that black women struggled to advance to senior positions due to different challenges that they encountered. The study is finalised by the participants providing recommendations in terms of how the representation of black women could be improved.
- Full Text:
- Date Issued: 2017
- Authors: Peacock, Brenda Thandiwe
- Date: 2017
- Subjects: Women bankers -- South Africa Bank management -- Women -- South Africa , Women executives -- South Africa Leadership in women -- South Africa Minorities -- Employment -- South Africa
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10948/19695 , vital:28936
- Description: The main purpose of this qualitative research study was to investigate strategies to improve the representation of black females in senior levels within the South African banking industry. This was done through investigating the challenges that black women face in their career advancement within the banking industry and the strategies which currently exist and can be implemented to improve this representation. In as much as the research is aimed at seeking strategies to improve black women representation in senior positions, it also seeks to understand the barriers experienced by black women in different levels within the industry as these levels serve as a pipeline for senior management. This problem was addressed through answering the research objectives. The research objectives were achieved through conducting a literature review to explore the existing research topic and conducting an empirical study. Empirical evidence was obtained through conducting semi-structured interviews with seven black women who are currently working in the banking sector. Semi-structured interviews were used due to the target population being specific to black women as well as the need to acquire in-depth knowledge from black women of their experiences in climbing the corporate ladder in the sector. The key findings of the research found that the participant’s perception was that black women were at the bottom, that black women were displaying behaviours that were inhibiting their progress to senior positions. The study also found that black women struggled to advance to senior positions due to different challenges that they encountered. The study is finalised by the participants providing recommendations in terms of how the representation of black women could be improved.
- Full Text:
- Date Issued: 2017
The perfomance of South African pilots on cognitive ability assessment
- Authors: Simpson, Sinombongo Mazulu
- Date: 2016
- Subjects: Intelligence tests -- South Africa , Airplanes -- Piloting -- Ability testing -- South Africa , Air pilots -- Social conditions
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10948/12813 , vital:27123
- Description: In South Africa, the issue of lack of black pilot skills is a most talked about topic in commercial airlines. Airlines need to find the right set of skills and attitude to operate safely and successfully. Airline safety remains a topic of discussion, therefore airlines need ensure robustness of their selection processes. There are many requirements that a person has to meet before s/he can be offered a first officer job at an airline. The majority of the pilots in South Africa are white males. The study aimed to determine if there are statistically significant differences in cognitive ability test results between Black and White applicants for pilot positions with a South Africa airline. The test battery included a verbal reasoning test, numerical reasoning test, visual thinking, abstract reasoning test, spatial reasoning test, short term memory test, monitoring ability test, hand-eye coordination, sense of orientation test, reactivity test, and a multi-tasking test. The data were extracted with permission from a database maintained on behalf of the airline by an online test provider and subjected to a statistical analysis using measures of central tendency, and spread, in order to report on the significance of the differences between the groups. There is strong evidence that the White group performed better than the Black group on the majority of the tests. It is recommended that further research is done in order to determine the causes of these differences. A comparative study of results on other airlines’ recruitment selection tests and an exploratory study of the impact of socio-economic factors, education quality and language on cognitive ability tests are recommended.
- Full Text:
- Date Issued: 2016
- Authors: Simpson, Sinombongo Mazulu
- Date: 2016
- Subjects: Intelligence tests -- South Africa , Airplanes -- Piloting -- Ability testing -- South Africa , Air pilots -- Social conditions
- Language: English
- Type: Thesis , Masters , MCom
- Identifier: http://hdl.handle.net/10948/12813 , vital:27123
- Description: In South Africa, the issue of lack of black pilot skills is a most talked about topic in commercial airlines. Airlines need to find the right set of skills and attitude to operate safely and successfully. Airline safety remains a topic of discussion, therefore airlines need ensure robustness of their selection processes. There are many requirements that a person has to meet before s/he can be offered a first officer job at an airline. The majority of the pilots in South Africa are white males. The study aimed to determine if there are statistically significant differences in cognitive ability test results between Black and White applicants for pilot positions with a South Africa airline. The test battery included a verbal reasoning test, numerical reasoning test, visual thinking, abstract reasoning test, spatial reasoning test, short term memory test, monitoring ability test, hand-eye coordination, sense of orientation test, reactivity test, and a multi-tasking test. The data were extracted with permission from a database maintained on behalf of the airline by an online test provider and subjected to a statistical analysis using measures of central tendency, and spread, in order to report on the significance of the differences between the groups. There is strong evidence that the White group performed better than the Black group on the majority of the tests. It is recommended that further research is done in order to determine the causes of these differences. A comparative study of results on other airlines’ recruitment selection tests and an exploratory study of the impact of socio-economic factors, education quality and language on cognitive ability tests are recommended.
- Full Text:
- Date Issued: 2016
Polynuclear biomolecular-supported rare earth coordination compounds : towards a new generation of lanthanide-based drugs
- Authors: Clark, Candyce
- Date: 2014
- Subjects: Polyols , Hydroxyl group , Rare earth metals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10439 , http://hdl.handle.net/10948/d1020778
- Description: Galactitol and cis,cis,cis-1,3,5-cyclohexanetriol are polyols that are ideal examples of model compounds for ligands with lanthanide ions as they have their hydroxyl groups in favourable steric arrangement. Several complexes were synthesised with both lanthanide chloride and lanthanide nitrate salts with galactitol, and a variety of structures, both polymeric and monomeric, were observed. In all these complexes, galactitol acted as a bridging molecule between the lanthanide ions. A notable difference was the lanthanum chloride–galactitol complex that showed both chloride and galactitol bridging. The lanthanide nitrate salts formed only polymeric complexes with galactitol. Not all of the complexes showed nitrate ions coordinated to the metal centre, and in the neodymium nitrate– galactitol complex, which shows both monodentate and bidentate coordination of the nitrate groups. The coordination of the nitrate ions was confirmed using both XRD and IR analysis. Two complexes with lanthanide chloride salts and cis,cis,cis-1,3,5-cyclohexanetriol were synthesised and analysed. Lanthanum chloride formed a polymeric complex, which showed extensive chloride bridging between the metal centres. Praseodymium chloride formed a dimeric complex. All complexes were analysed with single-crystal X-ray diffraction, 1H NMR, 13C NMR and IR spectroscopy.
- Full Text:
- Date Issued: 2014
- Authors: Clark, Candyce
- Date: 2014
- Subjects: Polyols , Hydroxyl group , Rare earth metals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10439 , http://hdl.handle.net/10948/d1020778
- Description: Galactitol and cis,cis,cis-1,3,5-cyclohexanetriol are polyols that are ideal examples of model compounds for ligands with lanthanide ions as they have their hydroxyl groups in favourable steric arrangement. Several complexes were synthesised with both lanthanide chloride and lanthanide nitrate salts with galactitol, and a variety of structures, both polymeric and monomeric, were observed. In all these complexes, galactitol acted as a bridging molecule between the lanthanide ions. A notable difference was the lanthanum chloride–galactitol complex that showed both chloride and galactitol bridging. The lanthanide nitrate salts formed only polymeric complexes with galactitol. Not all of the complexes showed nitrate ions coordinated to the metal centre, and in the neodymium nitrate– galactitol complex, which shows both monodentate and bidentate coordination of the nitrate groups. The coordination of the nitrate ions was confirmed using both XRD and IR analysis. Two complexes with lanthanide chloride salts and cis,cis,cis-1,3,5-cyclohexanetriol were synthesised and analysed. Lanthanum chloride formed a polymeric complex, which showed extensive chloride bridging between the metal centres. Praseodymium chloride formed a dimeric complex. All complexes were analysed with single-crystal X-ray diffraction, 1H NMR, 13C NMR and IR spectroscopy.
- Full Text:
- Date Issued: 2014
The lived experience of xenophobia within a South African university
- Authors: Sorensen, Thomas
- Date: 2012
- Subjects: Xenophobia -- South Africa , Multicultural education -- South Africa , Refugees -- Education -- South Africa , Immigrants -- Violence against -- South Africa
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:9944 , http://hdl.handle.net/10948/d1013272
- Description: South Africa’s borders were opened up in 1994 after Nelson Mandela became president. Since then South Africa has been battling xenophobia as immigrants from African nations started to come to the rainbow nation for a better life away from persecution, civil wars, and extreme poverty. Still, up until 2008 when massive riots broke out in Alexandria Township in Gauteng, xenophobia was an unknown word to most people outside academic, social work, and government circles. This has all changed now as 2008 will in all likelihood be remembered as the year when xenophobic violence erupted in South Africa and became a general feature in our daily media bulletins, prime time television broadcasts, and in our society as a whole. The South African university where the current study took place was also affected by xenophobia although without any displays of public violence. The current study sought to understand and describe the lived experience of xenophobia by individual, international, African students at a South African university. The study adopted a qualitative approach and the methodology used was multiple case studies employing Tesch’s model of content analysis. The findings of the study showed that the research participants, as a combined group, have lived through a wide range of xenophobic experiences excluding physical violence and that the research participants’ personal characteristics influenced their exposure to and experience of xenophobia. The study contributed to the understanding of the lived experience of xenophobia within a South African university by international, African students.
- Full Text:
- Date Issued: 2012
- Authors: Sorensen, Thomas
- Date: 2012
- Subjects: Xenophobia -- South Africa , Multicultural education -- South Africa , Refugees -- Education -- South Africa , Immigrants -- Violence against -- South Africa
- Language: English
- Type: Thesis , Masters , MA
- Identifier: vital:9944 , http://hdl.handle.net/10948/d1013272
- Description: South Africa’s borders were opened up in 1994 after Nelson Mandela became president. Since then South Africa has been battling xenophobia as immigrants from African nations started to come to the rainbow nation for a better life away from persecution, civil wars, and extreme poverty. Still, up until 2008 when massive riots broke out in Alexandria Township in Gauteng, xenophobia was an unknown word to most people outside academic, social work, and government circles. This has all changed now as 2008 will in all likelihood be remembered as the year when xenophobic violence erupted in South Africa and became a general feature in our daily media bulletins, prime time television broadcasts, and in our society as a whole. The South African university where the current study took place was also affected by xenophobia although without any displays of public violence. The current study sought to understand and describe the lived experience of xenophobia by individual, international, African students at a South African university. The study adopted a qualitative approach and the methodology used was multiple case studies employing Tesch’s model of content analysis. The findings of the study showed that the research participants, as a combined group, have lived through a wide range of xenophobic experiences excluding physical violence and that the research participants’ personal characteristics influenced their exposure to and experience of xenophobia. The study contributed to the understanding of the lived experience of xenophobia within a South African university by international, African students.
- Full Text:
- Date Issued: 2012
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