Carbonylation of cyclohexene with carbon dioxide (CO2) using transition metals as heterogeneous and homogeneous catalysts
- Authors: Sekaleli, Bafokeng Thabelo
- Date: 2024-10-11
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464565 , vital:76522
- Description: From a green chemistry perspective, carbon dioxide (CO2) emerges as an appealing C1 synthon, given its abundance in the atmosphere and cost-effectiveness. Many essential chemicals for daily life are derived from fossilized carbon sources like coal, petroleum, and natural gas. However, the by-product of these processes, CO2, poses environmental risks when excessively emitted as a greenhouse gas. Achieving a balance between carbon emissions and removal is crucial to address environmental concerns surrounding CO2. Utilizing CO2 as a C1 source in organic synthesis holds promise for mitigating this balance in the long term. Combining CO2 with other underutilized fine chemicals, such as alkanes, alkenes, and alkynes, to produce more valuable platform chemicals presents an economically viable strategy due to carbon dioxide’s abundance, low cost, and recyclability. Despite its simplicity, CO2's high thermodynamic stability and low kinetic reactivity, owing to its highly oxidized state, pose challenges to its use as a feedstock. Overcoming these hurdles requires catalysts to enhance CO2 reactivity. Our work focuses on developing and employing catalytic systems capable of activating CO2 as a C1 synthon in reactions with cyclohexene and a reducing agent to yield carboxylic acids or esters. In one approach, we have developed heterogeneous catalyst systems comprising transition metals (Au, Fe, Ni, Ru) supported on metal oxide (TiO2). Characterization techniques such as TEM, EDX, UV-Vis, BET, and XRD were used to study the properties of these materials. The catalysts were evaluated in a reaction involving cyclohexene, CO2, and H2O. In another approach, we explored the use of cyclo-tris(tetracarbonylruthenium) [Ru3(CO)12] as a homogeneous catalyst in a reaction involving cyclohexene, methanol, and CO2 in the presence of an ionic liquid, 1-Butyl-3-methylimidazolium chloride ([BMIM]+Cl-). 1H NMR and ATR-FT-IR were utilized to characterize [BMIM]+Cl-. The reaction product was characterised utilizing GC-MS. Upon seeing that Ru3(CO)12 changes color from orange to black when exposed to heat, an investigation was undertaken on the kind of transformations that the catalyst undergoes. This investigation was carried out with the hopes of finding the structures that could be resulting from Ru3(CO)12 during the reaction and their significance to it. The orange and black Ru complexes were characterized utilizing DSC, TGA, ATR-FT-IR and PXRD. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
- Authors: Sekaleli, Bafokeng Thabelo
- Date: 2024-10-11
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464565 , vital:76522
- Description: From a green chemistry perspective, carbon dioxide (CO2) emerges as an appealing C1 synthon, given its abundance in the atmosphere and cost-effectiveness. Many essential chemicals for daily life are derived from fossilized carbon sources like coal, petroleum, and natural gas. However, the by-product of these processes, CO2, poses environmental risks when excessively emitted as a greenhouse gas. Achieving a balance between carbon emissions and removal is crucial to address environmental concerns surrounding CO2. Utilizing CO2 as a C1 source in organic synthesis holds promise for mitigating this balance in the long term. Combining CO2 with other underutilized fine chemicals, such as alkanes, alkenes, and alkynes, to produce more valuable platform chemicals presents an economically viable strategy due to carbon dioxide’s abundance, low cost, and recyclability. Despite its simplicity, CO2's high thermodynamic stability and low kinetic reactivity, owing to its highly oxidized state, pose challenges to its use as a feedstock. Overcoming these hurdles requires catalysts to enhance CO2 reactivity. Our work focuses on developing and employing catalytic systems capable of activating CO2 as a C1 synthon in reactions with cyclohexene and a reducing agent to yield carboxylic acids or esters. In one approach, we have developed heterogeneous catalyst systems comprising transition metals (Au, Fe, Ni, Ru) supported on metal oxide (TiO2). Characterization techniques such as TEM, EDX, UV-Vis, BET, and XRD were used to study the properties of these materials. The catalysts were evaluated in a reaction involving cyclohexene, CO2, and H2O. In another approach, we explored the use of cyclo-tris(tetracarbonylruthenium) [Ru3(CO)12] as a homogeneous catalyst in a reaction involving cyclohexene, methanol, and CO2 in the presence of an ionic liquid, 1-Butyl-3-methylimidazolium chloride ([BMIM]+Cl-). 1H NMR and ATR-FT-IR were utilized to characterize [BMIM]+Cl-. The reaction product was characterised utilizing GC-MS. Upon seeing that Ru3(CO)12 changes color from orange to black when exposed to heat, an investigation was undertaken on the kind of transformations that the catalyst undergoes. This investigation was carried out with the hopes of finding the structures that could be resulting from Ru3(CO)12 during the reaction and their significance to it. The orange and black Ru complexes were characterized utilizing DSC, TGA, ATR-FT-IR and PXRD. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
Co-crystal formation of pharmaceutical and veterinary tranquilizer molecules
- Mngwengwe, Bongeka Naledi Precious
- Authors: Mngwengwe, Bongeka Naledi Precious
- Date: 2024-10-11
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464532 , vital:76519
- Description: Midazolam, a 1,4-benzodiazepine derivative is commonly used to treat anxiety, insomnia and may be used as a sedative in anaesthesia as it has calming, anti-convulsant and muscle relaxant properties. Midazolam has a rapid onset but a short duration of action resulting in fewer adverse effects. Midazolam also has the potential to form insoluble crystalline precipitates in pharmaceutical dosage forms such as syrups and solutions, which is a challenge in formulation and process development activities. The primary goal of this research was to prepare multicomponent crystals of midazolam free base, specifically targeting interactions with coformers structurally similar to methyl paraben. Key preparation techniques included neat grinding, liquid-assisted grinding, and slow evaporation. The resulting solid forms were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction (PXRD). In addition, Single-Crystal X-Ray Diffraction (SCXRD) was used to elucidate detailed structural information on the novel multicomponent crystals formed. Successful preparation of midazolam free base from the hydrochloride salt was confirmed through FTIR, DSC, and PXRD analysis. Different co-crystals and salts of midazolam with coformers such as salicylic acid (SA), benzoic acid (BA), 3-hydroxybenzoic acid (3-HBA) and p-aminobenzoic acid (PABA) were synthesized and characterized. The structure of the single crystal obtained from a veterinary tranquilizer solution was solved and found to be a salt that had formed between midazolam free base, midazolam HCl, and methyl paraben. This finding inspired further investigation of similar multicomponent crystals of midazolam and methyl paraben analogues. This study demonstrated the effectiveness of both mechanochemical and slow evaporation methods for the preparation of multicomponent crystals. PXRD and DSC provided insights into the stability and purity of the crystals that had formed and the differences in melting points and PXRD patterns were particularly important in this regard. Differences in FTIR spectra were used to distinguish between different solid forms and to confirm the successful formation of new solid forms. Extensive searches in the Cambridge Structural Database (CSD) confirmed that the multicomponent crystals of midazolam, such as MDZ‧SA, MDZ‧BA, MDZ‧3-HBA, and MDZ‧PABA, had not previously been reported, highlighting the novelty of these findings. The research successfully isolated and characterized several novel multicomponent crystals of midazolam, demonstrating the potential of mechanochemistry and solvent evaporation techniques in the development of pharmaceutical and veterinary medicinal applications. These findings contribute to the understanding of cocrystal formation and provide a foundation for future studies in which the stability and efficacy of midazolam-based formulations can be evaluated. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
- Authors: Mngwengwe, Bongeka Naledi Precious
- Date: 2024-10-11
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464532 , vital:76519
- Description: Midazolam, a 1,4-benzodiazepine derivative is commonly used to treat anxiety, insomnia and may be used as a sedative in anaesthesia as it has calming, anti-convulsant and muscle relaxant properties. Midazolam has a rapid onset but a short duration of action resulting in fewer adverse effects. Midazolam also has the potential to form insoluble crystalline precipitates in pharmaceutical dosage forms such as syrups and solutions, which is a challenge in formulation and process development activities. The primary goal of this research was to prepare multicomponent crystals of midazolam free base, specifically targeting interactions with coformers structurally similar to methyl paraben. Key preparation techniques included neat grinding, liquid-assisted grinding, and slow evaporation. The resulting solid forms were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction (PXRD). In addition, Single-Crystal X-Ray Diffraction (SCXRD) was used to elucidate detailed structural information on the novel multicomponent crystals formed. Successful preparation of midazolam free base from the hydrochloride salt was confirmed through FTIR, DSC, and PXRD analysis. Different co-crystals and salts of midazolam with coformers such as salicylic acid (SA), benzoic acid (BA), 3-hydroxybenzoic acid (3-HBA) and p-aminobenzoic acid (PABA) were synthesized and characterized. The structure of the single crystal obtained from a veterinary tranquilizer solution was solved and found to be a salt that had formed between midazolam free base, midazolam HCl, and methyl paraben. This finding inspired further investigation of similar multicomponent crystals of midazolam and methyl paraben analogues. This study demonstrated the effectiveness of both mechanochemical and slow evaporation methods for the preparation of multicomponent crystals. PXRD and DSC provided insights into the stability and purity of the crystals that had formed and the differences in melting points and PXRD patterns were particularly important in this regard. Differences in FTIR spectra were used to distinguish between different solid forms and to confirm the successful formation of new solid forms. Extensive searches in the Cambridge Structural Database (CSD) confirmed that the multicomponent crystals of midazolam, such as MDZ‧SA, MDZ‧BA, MDZ‧3-HBA, and MDZ‧PABA, had not previously been reported, highlighting the novelty of these findings. The research successfully isolated and characterized several novel multicomponent crystals of midazolam, demonstrating the potential of mechanochemistry and solvent evaporation techniques in the development of pharmaceutical and veterinary medicinal applications. These findings contribute to the understanding of cocrystal formation and provide a foundation for future studies in which the stability and efficacy of midazolam-based formulations can be evaluated. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
Cocrystals, salts and eutectics of anti-tuberculosis medicines
- Authors: Matlapeng, Tsebang Alice
- Date: 2024-10-11
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464521 , vital:76518
- Description: Tuberculosis remains as a prominent cause of death worldwide. This infectious disease is treated with first and second line drugs. However, challenges of multi drug resistant tuberculosis and adverse side effects such as depletion of essential B group vitamins in the body by first line drugs, as well as poor physicochemical properties of second line drugs persist. Cocrystallisation of anti-tubercular drugs with various coformers has therefore been used as an alternative method to improve the physicochemical properties of active pharmaceutical ingredients (API) while maintaining their efficacy. The main objective of this study was to carry out cocrystal screening of anti-tubercular API and vitamin B coformers to make drug-drug or drug-vitamin multicomponent complexes. Preparation of the multicomponent complexes was carried out by mechanochemical grinding (neat grinding (NG), liquid assisted grinding (LAG) and slow evaporation. All complexes were characterised using Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and crystal structures were elucidated using single-crystal X-ray diffraction (SCXRD). The cocrystal screening resulted in the formation of various solid forms, which included cocrystals, salts and eutectic products. Two cocrystals of 4-aminosalicylic acid (PAS) were isolated and characterised. The cocrystal of PAS with isoniazid (INH) demonstrated similar characteristics for both the bulk crystalline material and milled materials. The cocrystal of PAS and pyrazinamide (PYR) prepared using mechanochemical synthesis was met with challenges, while difficulties were also encountered in obtaining suitable crystals for SCXRD analysis. The ground and recrystallised samples of the PAS and pyrazinecarboxylic acid (PCBA) showed distinct differences in their thermal behaviour, with SCXRD revealing the decomposition product phenolammonium-pyrazinecarboxylate salt ‘sans’ the CO2 moiety. Salt formation involving pyridoxine (PN) yielded a salt hydrate with PAS (PN-PAS) and an anhydrous salt with PCBA (PN-PCBA). Both salts exhibited very complex packing arrangements with equally complex thermal behaviour depending on the solvent used during preparation, and the method of preparation. Three eutectic systems involving INH with PYR, PN and pyridoxine hydrochloride (PNꞏHCl) were identified, and their phase diagrams were constructed from DSC data. The eutectic compositions obtained were 1:1 for INH:PYR, 1:1 for INH:PN and 6:4 for INH:PNꞏHCl. Finally, a total of eight multicomponent complexes were prepared using selected API and vitamin B6 components. The results presented here provide motivation for further investigation and evaluation of the pharmacochemical properties of these API. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
- Authors: Matlapeng, Tsebang Alice
- Date: 2024-10-11
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464521 , vital:76518
- Description: Tuberculosis remains as a prominent cause of death worldwide. This infectious disease is treated with first and second line drugs. However, challenges of multi drug resistant tuberculosis and adverse side effects such as depletion of essential B group vitamins in the body by first line drugs, as well as poor physicochemical properties of second line drugs persist. Cocrystallisation of anti-tubercular drugs with various coformers has therefore been used as an alternative method to improve the physicochemical properties of active pharmaceutical ingredients (API) while maintaining their efficacy. The main objective of this study was to carry out cocrystal screening of anti-tubercular API and vitamin B coformers to make drug-drug or drug-vitamin multicomponent complexes. Preparation of the multicomponent complexes was carried out by mechanochemical grinding (neat grinding (NG), liquid assisted grinding (LAG) and slow evaporation. All complexes were characterised using Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and crystal structures were elucidated using single-crystal X-ray diffraction (SCXRD). The cocrystal screening resulted in the formation of various solid forms, which included cocrystals, salts and eutectic products. Two cocrystals of 4-aminosalicylic acid (PAS) were isolated and characterised. The cocrystal of PAS with isoniazid (INH) demonstrated similar characteristics for both the bulk crystalline material and milled materials. The cocrystal of PAS and pyrazinamide (PYR) prepared using mechanochemical synthesis was met with challenges, while difficulties were also encountered in obtaining suitable crystals for SCXRD analysis. The ground and recrystallised samples of the PAS and pyrazinecarboxylic acid (PCBA) showed distinct differences in their thermal behaviour, with SCXRD revealing the decomposition product phenolammonium-pyrazinecarboxylate salt ‘sans’ the CO2 moiety. Salt formation involving pyridoxine (PN) yielded a salt hydrate with PAS (PN-PAS) and an anhydrous salt with PCBA (PN-PCBA). Both salts exhibited very complex packing arrangements with equally complex thermal behaviour depending on the solvent used during preparation, and the method of preparation. Three eutectic systems involving INH with PYR, PN and pyridoxine hydrochloride (PNꞏHCl) were identified, and their phase diagrams were constructed from DSC data. The eutectic compositions obtained were 1:1 for INH:PYR, 1:1 for INH:PN and 6:4 for INH:PNꞏHCl. Finally, a total of eight multicomponent complexes were prepared using selected API and vitamin B6 components. The results presented here provide motivation for further investigation and evaluation of the pharmacochemical properties of these API. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Date Issued: 2024-10-11
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