Solid state thermal decomposition of amide complexes of nickel(II) chloride
- Nelwamondo, Aubrey Ndifelani
- Authors: Nelwamondo, Aubrey Ndifelani
- Date: 1997
- Subjects: Decomposition (Chemistry) Materials -- Thermal properties Amides
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4345 , http://hdl.handle.net/10962/d1005008
- Description: The thermal decompositions of a series of amide complexes of nickel(II) chloride have been studied. Thermochemical, kinetic, structure and solid-state stability correlations have been investigated. Complexes containing homologous amide ligands (L) of the form NiLCℓ₂, Ni₃L₂Cℓ₆, Ni₃LCℓ₆, NiL₂Cℓ₂(2H₂0) and ML₂Cℓ₂ (where M = Ni(II), Co(II) or Cu(II)) have been prepared. Chemical analysis, spectral and thermogravimetric measurements were used to characterize the complexes and their decomposition stoichiometries. Three sets of reactions were identified as yielding stable products in a single step: (i) NiLCℓ₂ (s) → NiCℓ₂ (s) + L (g) (ii) Ni₃LCℓ₆ (s) → 3NiCℓ₂ (s) + 2L (g) (iii) Ni₃LCℓ₆ (s) → 3NiCℓ₂ (s) + L (g) Characterization of the processes in the ML₂Cℓ₂ and NiL₂Cℓ₂(2H₂0) complexes was not straightforward. Reaction enthalpies (ΔH) were determined using DSC. The orders of the reaction onset temperatures (Tc), peak temperatures (Tmax) and ΔHL values for the NiCℓ₂ system were: N-methylacetamide < acetamide < N-methylformamide, suggesting the importance of steric hindrance of the methyl-substituent groups in the amide skeleton. In the Ni₃LCℓ₆, NiL₂Cℓ₂(2H₂0) and ML₂Cℓ₂ systems no simple orders could be deduced. The Te and Tmax sequences obtained from analogous metal(II) chloride complexes indicated that the copper(II) complexes were the least stable. The kinetics of the loss of L from NiLCℓ₂ complexes were investigated using isothermal TG, non-isothermal TG and DSC measurements. The contracting geometry models described the course of the decompositions in the most satisfactory manner. Apparent activation energies ( Ea) were estimated from Arrhenius plots of rate coefficients from: (i) an approximate zero-order relationship, (ii) the contracting-area (R2) and contracting-volume (R3) equations, (iii) a new empirical (B2) expression, (iv) the half-life ( 1/t₀.₅) and (v) the characteristic feature of the rate-time curve ( 1/tmax/2 ). The non-dependence of Ea on the rate equation used supports the reliability of the kinetic parameters. Non-isothermal experiments were analyzed by the Coats-Redfern, the modified BorchardtDaniels and the Kissinger methods. Arrhenius parameters were in keeping with results from the isothermal kinetic measurements. The values of Ea obtained for the NiLCℓ₂ system increased with an increase in basicity of the amide ligands. No straightforward correlation was found between Ea and Te, Tmax, ΔHL or spectral properties.
- Full Text:
- Date Issued: 1997
- Authors: Nelwamondo, Aubrey Ndifelani
- Date: 1997
- Subjects: Decomposition (Chemistry) Materials -- Thermal properties Amides
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4345 , http://hdl.handle.net/10962/d1005008
- Description: The thermal decompositions of a series of amide complexes of nickel(II) chloride have been studied. Thermochemical, kinetic, structure and solid-state stability correlations have been investigated. Complexes containing homologous amide ligands (L) of the form NiLCℓ₂, Ni₃L₂Cℓ₆, Ni₃LCℓ₆, NiL₂Cℓ₂(2H₂0) and ML₂Cℓ₂ (where M = Ni(II), Co(II) or Cu(II)) have been prepared. Chemical analysis, spectral and thermogravimetric measurements were used to characterize the complexes and their decomposition stoichiometries. Three sets of reactions were identified as yielding stable products in a single step: (i) NiLCℓ₂ (s) → NiCℓ₂ (s) + L (g) (ii) Ni₃LCℓ₆ (s) → 3NiCℓ₂ (s) + 2L (g) (iii) Ni₃LCℓ₆ (s) → 3NiCℓ₂ (s) + L (g) Characterization of the processes in the ML₂Cℓ₂ and NiL₂Cℓ₂(2H₂0) complexes was not straightforward. Reaction enthalpies (ΔH) were determined using DSC. The orders of the reaction onset temperatures (Tc), peak temperatures (Tmax) and ΔHL values for the NiCℓ₂ system were: N-methylacetamide < acetamide < N-methylformamide, suggesting the importance of steric hindrance of the methyl-substituent groups in the amide skeleton. In the Ni₃LCℓ₆, NiL₂Cℓ₂(2H₂0) and ML₂Cℓ₂ systems no simple orders could be deduced. The Te and Tmax sequences obtained from analogous metal(II) chloride complexes indicated that the copper(II) complexes were the least stable. The kinetics of the loss of L from NiLCℓ₂ complexes were investigated using isothermal TG, non-isothermal TG and DSC measurements. The contracting geometry models described the course of the decompositions in the most satisfactory manner. Apparent activation energies ( Ea) were estimated from Arrhenius plots of rate coefficients from: (i) an approximate zero-order relationship, (ii) the contracting-area (R2) and contracting-volume (R3) equations, (iii) a new empirical (B2) expression, (iv) the half-life ( 1/t₀.₅) and (v) the characteristic feature of the rate-time curve ( 1/tmax/2 ). The non-dependence of Ea on the rate equation used supports the reliability of the kinetic parameters. Non-isothermal experiments were analyzed by the Coats-Redfern, the modified BorchardtDaniels and the Kissinger methods. Arrhenius parameters were in keeping with results from the isothermal kinetic measurements. The values of Ea obtained for the NiLCℓ₂ system increased with an increase in basicity of the amide ligands. No straightforward correlation was found between Ea and Te, Tmax, ΔHL or spectral properties.
- Full Text:
- Date Issued: 1997
Synthetic and physical organic studies of chromone derivatives
- Ramaite, Ipfani David Isaiah
- Authors: Ramaite, Ipfani David Isaiah
- Date: 1997
- Subjects: Benzopyrans Heterocyclic compounds -- Derivatives Coumarins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4380 , http://hdl.handle.net/10962/d1005045
- Description: A range of chromone-2-carboxylic acids has been prepared by condensing suitably substituted 2-hydroxyacetophenones with diethyl oxalate. pK₂ Studies of these acids revealed that 6- or 7-methoxy substituents decreased acidity while the 6-nitro group enhanced acidity; the strongest acid was the 3-chloro derivative, the increase in acidity being attributed to steric inhibition of acid-weakening delocalisation between the carboxyl group and the chromone system. Various chromone-2-carboxamides, derived from acid chloride precursors, were converted to polysubstituted acrylamides by nucleophilic ring-opening with selected amine nucleophiles. The main fragmentation patterns exhibited by these acrylamides were elucidated using a combination of low resolution, high resolution and meta-stable peak analysis, while the effect of substituents on the simultaneous internal rotation involving the carboxamide and enamine moieties were studied using dynamic NMR spectroscopy. Rotational barriers of ca. 67.1 kJmol ̄¹ and ca. 102 kJmol ̄¹ were found for the enamine and amide rotors, respectively. Several synthetic pathways were followed to prepare a series of 2-(N,N-dialkylamino)chromones which were subjected to detailed mass spectral analysis. In addition to substituent-specific fragmentations , the 2-aminochromones appear to fragment via 3 major pathways. The effect of substituents on the internal rotation of the amino moeity was investigated by variable temperature ¹H NMR spectroscopy and the resulting DNMR data was used to calculate the rotational barriers. Examination of the data reveals that the electron-releasing 6- and 7- substituents reduce the C-NMe₂ rotational barrier to ca. 43.5 kJmol ̄¹ , while the nitro analogue has the largest rotational barrier (ca. 46.1 kJmol ̄¹) because of the electron-withdrawing effect of this substituent.
- Full Text:
- Date Issued: 1997
- Authors: Ramaite, Ipfani David Isaiah
- Date: 1997
- Subjects: Benzopyrans Heterocyclic compounds -- Derivatives Coumarins
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4380 , http://hdl.handle.net/10962/d1005045
- Description: A range of chromone-2-carboxylic acids has been prepared by condensing suitably substituted 2-hydroxyacetophenones with diethyl oxalate. pK₂ Studies of these acids revealed that 6- or 7-methoxy substituents decreased acidity while the 6-nitro group enhanced acidity; the strongest acid was the 3-chloro derivative, the increase in acidity being attributed to steric inhibition of acid-weakening delocalisation between the carboxyl group and the chromone system. Various chromone-2-carboxamides, derived from acid chloride precursors, were converted to polysubstituted acrylamides by nucleophilic ring-opening with selected amine nucleophiles. The main fragmentation patterns exhibited by these acrylamides were elucidated using a combination of low resolution, high resolution and meta-stable peak analysis, while the effect of substituents on the simultaneous internal rotation involving the carboxamide and enamine moieties were studied using dynamic NMR spectroscopy. Rotational barriers of ca. 67.1 kJmol ̄¹ and ca. 102 kJmol ̄¹ were found for the enamine and amide rotors, respectively. Several synthetic pathways were followed to prepare a series of 2-(N,N-dialkylamino)chromones which were subjected to detailed mass spectral analysis. In addition to substituent-specific fragmentations , the 2-aminochromones appear to fragment via 3 major pathways. The effect of substituents on the internal rotation of the amino moeity was investigated by variable temperature ¹H NMR spectroscopy and the resulting DNMR data was used to calculate the rotational barriers. Examination of the data reveals that the electron-releasing 6- and 7- substituents reduce the C-NMe₂ rotational barrier to ca. 43.5 kJmol ̄¹ , while the nitro analogue has the largest rotational barrier (ca. 46.1 kJmol ̄¹) because of the electron-withdrawing effect of this substituent.
- Full Text:
- Date Issued: 1997
Computer modelling of pyrotechnic combustion
- Authors: Taylor, Steven John
- Date: 1996
- Subjects: Combustion -- Computer simulation
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4426 , http://hdl.handle.net/10962/d1006913
- Description: One of the most important industrial uses of pyrotechnic compositions is as delay fuses in electric detonators. Many factors influence the rate of burning of such fuses. These include (a) the primary choice of chemical components, followed by (b) the physical properties of these components, particularly the particle-size and distribution of the fuel, (c) the composition of the system chosen and (d) the presence of additives and/or impurities. A full experimental study of the influences of even a few of these factors, while attempting to hold other potential variables constant, would be extremely time consuming and hence attention has been focused on the possibilities of modelling pyrotechnic combustion. Various approaches to the modelling of pyrotechnic combustion are discussed. These include:- (i) one-dimensional finite-difference models; (ii) two-dimensional finite-element models; (iii) particle-packing considerations; (iv) Monte Carlo models. Predicted behaviour is compared with extensive experimental information for the widely-used antimony/potassium permanganate pyrotechnic system, and the tungsten /potassium dichromate pyrotechnic system. The one-dimensional finite-difference model was investigated to give a simple means of investigating the effects of some parameters on the combustion of a pyrotechnic. The two-dimensional finite-difference model used similar inputs, but at the expense of considerably more computer power, gave more extensive information such as the shape of the burning front and the temperature gradients throughout the column and within the casing material. Both these models gave improved results when allowance was made for autocatalytic kinetics in place of the usual assumption of an "order-of-reaction", n ≤ 1. The particle-packing model investigated the qualitative relationship between the maximum burning rate of a pyrotechnic system and the maximum number of contact points (per 1.00 g composition) calculated for that system. Qualitative agreement was found for those systems which are presumed to burn mainly via solid-solid reactions. The Monte Carlo model investigated the effect of the random packing of fuel and oxidant particles on the variability of the burning rate of a pyrotechnic composition.
- Full Text:
- Date Issued: 1996
- Authors: Taylor, Steven John
- Date: 1996
- Subjects: Combustion -- Computer simulation
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4426 , http://hdl.handle.net/10962/d1006913
- Description: One of the most important industrial uses of pyrotechnic compositions is as delay fuses in electric detonators. Many factors influence the rate of burning of such fuses. These include (a) the primary choice of chemical components, followed by (b) the physical properties of these components, particularly the particle-size and distribution of the fuel, (c) the composition of the system chosen and (d) the presence of additives and/or impurities. A full experimental study of the influences of even a few of these factors, while attempting to hold other potential variables constant, would be extremely time consuming and hence attention has been focused on the possibilities of modelling pyrotechnic combustion. Various approaches to the modelling of pyrotechnic combustion are discussed. These include:- (i) one-dimensional finite-difference models; (ii) two-dimensional finite-element models; (iii) particle-packing considerations; (iv) Monte Carlo models. Predicted behaviour is compared with extensive experimental information for the widely-used antimony/potassium permanganate pyrotechnic system, and the tungsten /potassium dichromate pyrotechnic system. The one-dimensional finite-difference model was investigated to give a simple means of investigating the effects of some parameters on the combustion of a pyrotechnic. The two-dimensional finite-difference model used similar inputs, but at the expense of considerably more computer power, gave more extensive information such as the shape of the burning front and the temperature gradients throughout the column and within the casing material. Both these models gave improved results when allowance was made for autocatalytic kinetics in place of the usual assumption of an "order-of-reaction", n ≤ 1. The particle-packing model investigated the qualitative relationship between the maximum burning rate of a pyrotechnic system and the maximum number of contact points (per 1.00 g composition) calculated for that system. Qualitative agreement was found for those systems which are presumed to burn mainly via solid-solid reactions. The Monte Carlo model investigated the effect of the random packing of fuel and oxidant particles on the variability of the burning rate of a pyrotechnic composition.
- Full Text:
- Date Issued: 1996
The pyrrolizidine alkaloids of Senecio chrysocoma and Senecio paniculatus
- Authors: Logie, Catherine Gwynedd
- Date: 1996
- Subjects: Senecio -- Analysis Pyrrolizidines Botanical chemistry
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4339 , http://hdl.handle.net/10962/d1005000
- Description: In order to compare the pyrrolizidine alkaloid content of two closely related species, Senecio chrysocoma and S. paniculatus, nine populations of plants distributed between the two species, were examined. Three novel pyrrolizidine alkaloids, 7ß-angelyl-l-methylene-8∝-pyrrolizidine, 7ß-angelyl-l-methylene-8∝-pyrrolizidine and 7ß-angelyl-l-methyleneSO!-pyrrolizidine-4-oxide, as well as eight known pyrrolizidine alkaloids, 7-angelylhastanecine, 9-angelylhastanecine, 7-angelylplatynecine, 9-angelylplatynecine, 9-angelylplatynecine-4-oxide, sarracine, neosarracine and retrorsine, were isolated and identified by NMR and GC-MS techniques. Traces of five tiglyl isomers, 9-tiglylplatynecine, 9-tigl ylplatynecine-4-oxide, 7ß-tiglyl-l-methylene-8∝-pyrrolizidine, sarranicine and neosarranicine, were also isolated and tentatively identified; however, these compounds could have been artefacts of the extraction and analytical procedures. While both species of plant investigated, S. chrysocoma and S. paniculatus, were found to be morphologically different, their pyrrolizidine alkaloid content was, in fact, very similar. The presence of retrorsine in S. paniculatus plant extracts, but not in those from S. chrysocoma plants, was the only major chemical difference observed. It is perhaps significant that retrorsine was the only macrocyclic pyrrolizidine to be identified. A comprehensive, computerised database of physical data for pyrrolizidine alkaloids has been compiled, which has facilitated the identification of new pyrrolizidines and the examination of trends in proton and carbon-13 NMR data for pyrrolizidine alkaloids. A stereospecific synthesis of 7ß-angelyl-l-methylene-8∝-pyrrolizidine was undertaken toconfirm the absolute stereochemistry of the product isolated from S. chrysocoma and S. paniculatus. An inseparable 5:2 mixture of 7ß-angelyl-l-methylene-8∝-pyrrolizidine and 7ß-angelyl-l,2-didehydro-l-methyl-8∝-pyrrolizidine, together with a small amount of tiglyl isomer, was finally synthesised. The application of various chiral differentiating chromatographic and spectroscopic techniques confirmed that both the natural and synthetic products had the same stereochemistry, permitting the natural alkaloid to be identified as 7ß-angelyl-methylene-8∝-pyrrol izidine
- Full Text:
- Date Issued: 1996
- Authors: Logie, Catherine Gwynedd
- Date: 1996
- Subjects: Senecio -- Analysis Pyrrolizidines Botanical chemistry
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4339 , http://hdl.handle.net/10962/d1005000
- Description: In order to compare the pyrrolizidine alkaloid content of two closely related species, Senecio chrysocoma and S. paniculatus, nine populations of plants distributed between the two species, were examined. Three novel pyrrolizidine alkaloids, 7ß-angelyl-l-methylene-8∝-pyrrolizidine, 7ß-angelyl-l-methylene-8∝-pyrrolizidine and 7ß-angelyl-l-methyleneSO!-pyrrolizidine-4-oxide, as well as eight known pyrrolizidine alkaloids, 7-angelylhastanecine, 9-angelylhastanecine, 7-angelylplatynecine, 9-angelylplatynecine, 9-angelylplatynecine-4-oxide, sarracine, neosarracine and retrorsine, were isolated and identified by NMR and GC-MS techniques. Traces of five tiglyl isomers, 9-tiglylplatynecine, 9-tigl ylplatynecine-4-oxide, 7ß-tiglyl-l-methylene-8∝-pyrrolizidine, sarranicine and neosarranicine, were also isolated and tentatively identified; however, these compounds could have been artefacts of the extraction and analytical procedures. While both species of plant investigated, S. chrysocoma and S. paniculatus, were found to be morphologically different, their pyrrolizidine alkaloid content was, in fact, very similar. The presence of retrorsine in S. paniculatus plant extracts, but not in those from S. chrysocoma plants, was the only major chemical difference observed. It is perhaps significant that retrorsine was the only macrocyclic pyrrolizidine to be identified. A comprehensive, computerised database of physical data for pyrrolizidine alkaloids has been compiled, which has facilitated the identification of new pyrrolizidines and the examination of trends in proton and carbon-13 NMR data for pyrrolizidine alkaloids. A stereospecific synthesis of 7ß-angelyl-l-methylene-8∝-pyrrolizidine was undertaken toconfirm the absolute stereochemistry of the product isolated from S. chrysocoma and S. paniculatus. An inseparable 5:2 mixture of 7ß-angelyl-l-methylene-8∝-pyrrolizidine and 7ß-angelyl-l,2-didehydro-l-methyl-8∝-pyrrolizidine, together with a small amount of tiglyl isomer, was finally synthesised. The application of various chiral differentiating chromatographic and spectroscopic techniques confirmed that both the natural and synthetic products had the same stereochemistry, permitting the natural alkaloid to be identified as 7ß-angelyl-methylene-8∝-pyrrol izidine
- Full Text:
- Date Issued: 1996
Reactions of iron- and zinc-fuelled pyrotechnic systems
- Authors: Tribelhorn, Michael John
- Date: 1995
- Subjects: Detonators Peroxides Chemistry, Analytic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4341 , http://hdl.handle.net/10962/d1005003
- Description: A major industrial use of pyrotechnic compositions is as delay fuses in electric detonators. Suitable delay times may be achieved through (i) choice of chemical components (ii) adjustment of composition of the system chosen and, finally, (iii) adjustment of the length of fuse used. This study forms part of a survey of binary fuel/oxidant combinations in an attempt to provide some fundamental information on the first step above: (i) choice of chemical components. The complete survey has included studies of a single fuel in combination with one of a variety of oxidants, and studies of the oxidation of one of several different fuels separately by barium peroxide and strontium peroxide. This study is part of this second approach and the fuels chosen were iron and zinc powders, mainly for chemical reasons (including the potential for use of thermomagnetometry on the iron systems), but also for possible environmental advantages. The mixed oxide products of pyrotechnic combustion could also have some scientific and/or commercial value. The techniques used included thermal analyses of mixtures and their individual components, and measurements of temperature-time profiles during combustion. Thermodynamic and kinetic information was obtained under a variety of conditions and scanning electron microscopy and X-ray diffraction and microprobe analyses provided additional information. Possible mechanisms of reactions are discussed in detail. The practical conclusions were that any potential use which the Fe/peroxide systems may have as delay compositions, with burning-rates of from 3-30 mm s⁻¹, is offset by the susceptibility of the oxidants to reaction with water and CO₂ in the atmosphere. The Zn/BaO₂ and Zn/SrO₂ systems did not burn under compaction, and combustion of uncompacted powders was erratic. Zinc liquid (and probably zinc vapour) take part in the reaction and the gaseous nature of the combustion makes zinc-fuelled pyrotechnic systems unsuitable for delay applications. All the techniques used showed the heterogeneity of the solid residues of combustion. If these residues were to be of any value, they would need further conventional treatment involving grinding of the residue, possible adjustment of compositions, and calcining to produce uniform materials.
- Full Text:
- Date Issued: 1995
- Authors: Tribelhorn, Michael John
- Date: 1995
- Subjects: Detonators Peroxides Chemistry, Analytic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4341 , http://hdl.handle.net/10962/d1005003
- Description: A major industrial use of pyrotechnic compositions is as delay fuses in electric detonators. Suitable delay times may be achieved through (i) choice of chemical components (ii) adjustment of composition of the system chosen and, finally, (iii) adjustment of the length of fuse used. This study forms part of a survey of binary fuel/oxidant combinations in an attempt to provide some fundamental information on the first step above: (i) choice of chemical components. The complete survey has included studies of a single fuel in combination with one of a variety of oxidants, and studies of the oxidation of one of several different fuels separately by barium peroxide and strontium peroxide. This study is part of this second approach and the fuels chosen were iron and zinc powders, mainly for chemical reasons (including the potential for use of thermomagnetometry on the iron systems), but also for possible environmental advantages. The mixed oxide products of pyrotechnic combustion could also have some scientific and/or commercial value. The techniques used included thermal analyses of mixtures and their individual components, and measurements of temperature-time profiles during combustion. Thermodynamic and kinetic information was obtained under a variety of conditions and scanning electron microscopy and X-ray diffraction and microprobe analyses provided additional information. Possible mechanisms of reactions are discussed in detail. The practical conclusions were that any potential use which the Fe/peroxide systems may have as delay compositions, with burning-rates of from 3-30 mm s⁻¹, is offset by the susceptibility of the oxidants to reaction with water and CO₂ in the atmosphere. The Zn/BaO₂ and Zn/SrO₂ systems did not burn under compaction, and combustion of uncompacted powders was erratic. Zinc liquid (and probably zinc vapour) take part in the reaction and the gaseous nature of the combustion makes zinc-fuelled pyrotechnic systems unsuitable for delay applications. All the techniques used showed the heterogeneity of the solid residues of combustion. If these residues were to be of any value, they would need further conventional treatment involving grinding of the residue, possible adjustment of compositions, and calcining to produce uniform materials.
- Full Text:
- Date Issued: 1995
Synthetic and spectrometric studies of benzodioxepinone derivatives
- Authors: Gelebe, Aifheli Carlson
- Date: 1995
- Subjects: Benzodiazepines -- Research Flavonoids -- Research
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4382 , http://hdl.handle.net/10962/d1005047
- Description: An extensive range of oxygen and sulphur substituted benzodiazepine analogues has been synthesised via Baeyer-Villiger and Schmidt reactions of specially prepared flavanone and N-acetyl-4-quinolone precursors. Alternative, cyclisation routes have also been used to prepare some of these compounds. Ring-opening reactions of 1,5-benzodioxepinones have been investigated and a detailed kinetic-mechanistic study of the Baeyer-Villiger reaction of flavanones has been carried out using 1 H NMR spectroscopy to explain the observed regiochemistry of oxygen insertion. The electron-impact mass spectrometric fragmentation patterns of series of 4-aryl-l ,5-benzoxathiepinones, 3-aryl-4, I-benzoxathiepinones and 3-aryl-4,1-benzoxathiepines have been studied using a combination of low-resolution, highresolution and metastable-peak analyses. The 170 NMR spectroscopic properties of various oxygenated analogues have also been studied. The binding affinities of selected benzodiazepine analogues for rat brain benzodiazepine receptors have been evaluated using a radioreceptor assay technique; at certain concentrations, some of test compounds exhibited remarkable potentiation of diazepam binding, others the ability to displace diazepam from benzodiazepine receptors. A conformational analysis of the 7-membered ring systems has been undertaken, using lH NMR spectroscopic, computer modelling and x-ray crystallographic techniques, and certain conformational preferences have been identified.
- Full Text:
- Date Issued: 1995
- Authors: Gelebe, Aifheli Carlson
- Date: 1995
- Subjects: Benzodiazepines -- Research Flavonoids -- Research
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4382 , http://hdl.handle.net/10962/d1005047
- Description: An extensive range of oxygen and sulphur substituted benzodiazepine analogues has been synthesised via Baeyer-Villiger and Schmidt reactions of specially prepared flavanone and N-acetyl-4-quinolone precursors. Alternative, cyclisation routes have also been used to prepare some of these compounds. Ring-opening reactions of 1,5-benzodioxepinones have been investigated and a detailed kinetic-mechanistic study of the Baeyer-Villiger reaction of flavanones has been carried out using 1 H NMR spectroscopy to explain the observed regiochemistry of oxygen insertion. The electron-impact mass spectrometric fragmentation patterns of series of 4-aryl-l ,5-benzoxathiepinones, 3-aryl-4, I-benzoxathiepinones and 3-aryl-4,1-benzoxathiepines have been studied using a combination of low-resolution, highresolution and metastable-peak analyses. The 170 NMR spectroscopic properties of various oxygenated analogues have also been studied. The binding affinities of selected benzodiazepine analogues for rat brain benzodiazepine receptors have been evaluated using a radioreceptor assay technique; at certain concentrations, some of test compounds exhibited remarkable potentiation of diazepam binding, others the ability to displace diazepam from benzodiazepine receptors. A conformational analysis of the 7-membered ring systems has been undertaken, using lH NMR spectroscopic, computer modelling and x-ray crystallographic techniques, and certain conformational preferences have been identified.
- Full Text:
- Date Issued: 1995
Studies in asymmetric synthesis
- Authors: Ravindran, Swarnam Shanthi
- Date: 1994
- Subjects: Asymmetric synthesis Chirality Organic compounds -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4352 , http://hdl.handle.net/10962/d1005017
- Description: The stereoselectivity of TiCI₄-catalysed Mukaiyama reactions of a camphor acetal-derived chiral silyl enol ether with a range of substituted aromatic aldehydes has been examined. The enantiomeric excess in each of the resulting ß-hydroxy ketones, determined by ¹H NMR spectroscopy using the lanthanide chiral shift reagent Pr(Etcf₃), ranged between 9 and 13%. The stereo-directing potential of the camphor acetal as a chiral auxiliary in the α-benzylation of carboxylate esters has been studied; the acids were chosen to illustrate substituent effects on asymmetric induction. The observed diastereoselectivity increased with increasing steric bulk of the ester group and α-benzylation of the tert-butylacetate derivative proceeded with 48% diastereoselectivity. It is proposed that the enolate adopts an endo-s-trans conformation in the transition state and preferential attack by the electrophile at the somewhat less hindered Si-face is supported by both the optical rotation data and computer modelling studies. Reductive cleavage and hydrolysis of one of the benzylated esters furnished known products from whose optical rotation the configuration of the major diastereomer was established. In order to improve the steric advantage of Si-facial attack, methods of increasing the steric bulk of the blocking group were explored. A novel 2,2-propylenedioxy hydroxycamphor acetal and its 3,3-propylenedioxy analogue were prepared. Selected carboxylate esters of these propylenedioxy acetals were subjected to α-benzylation and the 2,2-(propylenedioxy)-3-exo-tert-butylacetate derivative showed a diastereoselectivity of 57% during a-benzylation. Hydrolysis of the abenzylated phenylacetate analogue offered the known 2,3-diphenylpropanoic acid whose optical rotation indicated the preferred configuration at the new chiral centre to be (R), a result which is consistent with the proposed approach of the electrophile to the less hindered Re-face of theendo-s-trans enolate moiety and reflects an inversion of the configurational bias observed with 2-v exo-carboxylate analogues. Attempts to prepare the monocatechol acetal of the hydroxy camphor derivative although unsuccessful, led to the isolation of two novel dibornyl ethers whose structures were established by 1- and 2-D NMR spectroscopy. A study of novel applications of camphor-derived auxiliaries in the asymmetric synthesis of α-amino acids has been initiated. The several approaches tried led to the preparation of three novel dural glycine derivatives in good yield
- Full Text:
- Date Issued: 1994
- Authors: Ravindran, Swarnam Shanthi
- Date: 1994
- Subjects: Asymmetric synthesis Chirality Organic compounds -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4352 , http://hdl.handle.net/10962/d1005017
- Description: The stereoselectivity of TiCI₄-catalysed Mukaiyama reactions of a camphor acetal-derived chiral silyl enol ether with a range of substituted aromatic aldehydes has been examined. The enantiomeric excess in each of the resulting ß-hydroxy ketones, determined by ¹H NMR spectroscopy using the lanthanide chiral shift reagent Pr(Etcf₃), ranged between 9 and 13%. The stereo-directing potential of the camphor acetal as a chiral auxiliary in the α-benzylation of carboxylate esters has been studied; the acids were chosen to illustrate substituent effects on asymmetric induction. The observed diastereoselectivity increased with increasing steric bulk of the ester group and α-benzylation of the tert-butylacetate derivative proceeded with 48% diastereoselectivity. It is proposed that the enolate adopts an endo-s-trans conformation in the transition state and preferential attack by the electrophile at the somewhat less hindered Si-face is supported by both the optical rotation data and computer modelling studies. Reductive cleavage and hydrolysis of one of the benzylated esters furnished known products from whose optical rotation the configuration of the major diastereomer was established. In order to improve the steric advantage of Si-facial attack, methods of increasing the steric bulk of the blocking group were explored. A novel 2,2-propylenedioxy hydroxycamphor acetal and its 3,3-propylenedioxy analogue were prepared. Selected carboxylate esters of these propylenedioxy acetals were subjected to α-benzylation and the 2,2-(propylenedioxy)-3-exo-tert-butylacetate derivative showed a diastereoselectivity of 57% during a-benzylation. Hydrolysis of the abenzylated phenylacetate analogue offered the known 2,3-diphenylpropanoic acid whose optical rotation indicated the preferred configuration at the new chiral centre to be (R), a result which is consistent with the proposed approach of the electrophile to the less hindered Re-face of theendo-s-trans enolate moiety and reflects an inversion of the configurational bias observed with 2-v exo-carboxylate analogues. Attempts to prepare the monocatechol acetal of the hydroxy camphor derivative although unsuccessful, led to the isolation of two novel dibornyl ethers whose structures were established by 1- and 2-D NMR spectroscopy. A study of novel applications of camphor-derived auxiliaries in the asymmetric synthesis of α-amino acids has been initiated. The several approaches tried led to the preparation of three novel dural glycine derivatives in good yield
- Full Text:
- Date Issued: 1994
Synthetic and spectroscopic studies of 1,4-benzodiazepine analogues
- Authors: Mphahlele, Malose Jack
- Date: 1994
- Subjects: Benzodiazepines Tranquilizing drugs
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4384 , http://hdl.handle.net/10962/d1005049
- Description: In this project, an extensive range of benzodiazepine analogues have been synthesised via Schmidt reaction of specially prepared flavanone, 4-quinolone and l-thioflavanone precursors; nitrogen insertion being effected by use of trimethylsilyl azide in trifluoroacetic acid. In some cases, several of the benzodiazepine analogues have also been prepared by alternative cyclisation routes. A detailed kinetic-mechanistic study of the Schmidt reaction of flavanones has been carried out using 'H NMR spectroscopy to explain the observed regiochemistry of nitrogen insertion. The reaction rates, for the formation of both amide and tetrazolo derivatives have been found to be influenced by the electronic effects of the A- and B-ring substituents. A series of benzodiazepine analogues have been shown to undergo regioselective A-ring chlorination with t-butylhypochlorite; the products being characterised by 'H NMR, IR and mass spectroscopy. The mass spectrometric fragmentation patterns of series of 2-aryl-4-quinolones, and 2-aryl-l ,4-benzodiazepinones and their tetrazolo[l ,5-dl analogues have been elucidated using a combination of low-resolution, high-resolution and metastable-peak analyses. The binding affinities of various benzodiazepine analogues for rat brain benzodiazepine receptors have been evaluated using a radioreceptor assay technique. Structure-activity relationships were investigated to establish the effects of various A-, B- and Coring substituents on binding affinity. The conformational preferences of selected systems have been studied using a combination of multi-pulse 'H NMR spectroscopy, X-ray crystallography and computer modelling techniques with a view to establishing the influence of conformation on binding affinity.
- Full Text:
- Date Issued: 1994
- Authors: Mphahlele, Malose Jack
- Date: 1994
- Subjects: Benzodiazepines Tranquilizing drugs
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4384 , http://hdl.handle.net/10962/d1005049
- Description: In this project, an extensive range of benzodiazepine analogues have been synthesised via Schmidt reaction of specially prepared flavanone, 4-quinolone and l-thioflavanone precursors; nitrogen insertion being effected by use of trimethylsilyl azide in trifluoroacetic acid. In some cases, several of the benzodiazepine analogues have also been prepared by alternative cyclisation routes. A detailed kinetic-mechanistic study of the Schmidt reaction of flavanones has been carried out using 'H NMR spectroscopy to explain the observed regiochemistry of nitrogen insertion. The reaction rates, for the formation of both amide and tetrazolo derivatives have been found to be influenced by the electronic effects of the A- and B-ring substituents. A series of benzodiazepine analogues have been shown to undergo regioselective A-ring chlorination with t-butylhypochlorite; the products being characterised by 'H NMR, IR and mass spectroscopy. The mass spectrometric fragmentation patterns of series of 2-aryl-4-quinolones, and 2-aryl-l ,4-benzodiazepinones and their tetrazolo[l ,5-dl analogues have been elucidated using a combination of low-resolution, high-resolution and metastable-peak analyses. The binding affinities of various benzodiazepine analogues for rat brain benzodiazepine receptors have been evaluated using a radioreceptor assay technique. Structure-activity relationships were investigated to establish the effects of various A-, B- and Coring substituents on binding affinity. The conformational preferences of selected systems have been studied using a combination of multi-pulse 'H NMR spectroscopy, X-ray crystallography and computer modelling techniques with a view to establishing the influence of conformation on binding affinity.
- Full Text:
- Date Issued: 1994
Synthetic and spectroscopic studies of indolizine derivatives
- Authors: Bode, Moira Leanne
- Date: 1994
- Subjects: Indole alkaloids -- Derivatives Spectrum analysis Chemistry, Organic DNA -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4385 , http://hdl.handle.net/10962/d1005050
- Description: The crystalline compound resulting from thermal cyclization of the Baylis-Hillman product, methyl 3-hydroxy-2-methylene-3-(2-pyridyl)propanoate, has been identified as the indolizine derivative, methyl indolizine-2-carboxylate, and this approach involving the reaction of pyridine-2-carboxaldehydes and acrylate analogues has been established as a general route to 2-substituted indolizines. The ease of cyclization the Baylis-Hillman products to indolizines has been shown to increase by converting the hydroxy group to an acetoxy group, and a range of acetylated Baylis-Hillman products were prepared and cyc1ized to the corresponding 2-substituted indolizines, generally in good overall yield. In the reaction of pyridine-2-carboxaldehyde and methyl vinyl ketone, the intermediate cyclized readily and directly to the corresponding indolizine. One- and two-dimensional ¹H and ¹³C NMR analysis of the 2-substituted indolizine products has permitted complete assignment of all ¹H and ¹³C NMR signals, as well as the measurement of all coupling constants for these compounds. A kinetic and mechanistic study has been conducted on the Baylis-Hillman reaction using ¹H NMR spectroscopy. A range of substrates has been examined and the reaction has been found to be third-order overall. A mechanism involving an addition - elimination sequence is proposed, which fits the kinetic data and accounts for observed substituent effects. Reaction of N,N-dimethylacrylamide with pyridine-2-carboxaldehyde in the presence of the tertiary amine catalyst, DABCO, in chloroform, yielded an unexpected product which has been identified by single crystal X-ray diffraction analysis as 1-(2,2,2-trichloro-1-hydroxyethyl)pyridine. Attempted extension of the general indolizine route to the preparation of chromene systems by reacting salicylaldehyde with methyl acrylate in the presence of DABCO, also led to an unexpected, crystalline material, identified by single crystal X-ray diffraction analysis as the coumarin derivative, 3-[(2-formylphenoxy)methyl]coumarin.A series of chloroquine analogues have been prepared from indolizine-2-carboxylic acid, pyrrolo[I,2-a]quinoline-2-carboxylic acid and imidazo[I,2-a]pyridine-2-carboxylic acid by reaction with suitable amines in the presence of the coupling reagent 1, I' -carbonyldiimidazole. This route has been shown to be a vast improvement on earlier procedures and has provided access to both secondary and tertiary indolizine-2-carboxamides. A range of N,N-dialkylindolizine-2-carboxamides have been prepared by this route, and the influence of substituents on their N-CO rotational energy barriers has been determined using variable temperature ¹H and ¹³C NMR techniques. Intercalation with natural DNA by both chloroquine and the synthesized chloroquine analogues has been examined using UV spectrophotometry, and ¹H and ³¹P NMR spectroscopy. The pyrrolo[I,2-a]quinolines have been shown to be DNA intercalators with binding affinities similar to that of the known antimalarial intercalator, chloroquine. In a preliminary study the synthesis of a short oligonucleotide has been undertaken and changes have been observed in the ¹H and ³¹P NMR spectra of the oligonucleotide on addition of the intercalator, chloroquine.
- Full Text:
- Date Issued: 1994
- Authors: Bode, Moira Leanne
- Date: 1994
- Subjects: Indole alkaloids -- Derivatives Spectrum analysis Chemistry, Organic DNA -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4385 , http://hdl.handle.net/10962/d1005050
- Description: The crystalline compound resulting from thermal cyclization of the Baylis-Hillman product, methyl 3-hydroxy-2-methylene-3-(2-pyridyl)propanoate, has been identified as the indolizine derivative, methyl indolizine-2-carboxylate, and this approach involving the reaction of pyridine-2-carboxaldehydes and acrylate analogues has been established as a general route to 2-substituted indolizines. The ease of cyclization the Baylis-Hillman products to indolizines has been shown to increase by converting the hydroxy group to an acetoxy group, and a range of acetylated Baylis-Hillman products were prepared and cyc1ized to the corresponding 2-substituted indolizines, generally in good overall yield. In the reaction of pyridine-2-carboxaldehyde and methyl vinyl ketone, the intermediate cyclized readily and directly to the corresponding indolizine. One- and two-dimensional ¹H and ¹³C NMR analysis of the 2-substituted indolizine products has permitted complete assignment of all ¹H and ¹³C NMR signals, as well as the measurement of all coupling constants for these compounds. A kinetic and mechanistic study has been conducted on the Baylis-Hillman reaction using ¹H NMR spectroscopy. A range of substrates has been examined and the reaction has been found to be third-order overall. A mechanism involving an addition - elimination sequence is proposed, which fits the kinetic data and accounts for observed substituent effects. Reaction of N,N-dimethylacrylamide with pyridine-2-carboxaldehyde in the presence of the tertiary amine catalyst, DABCO, in chloroform, yielded an unexpected product which has been identified by single crystal X-ray diffraction analysis as 1-(2,2,2-trichloro-1-hydroxyethyl)pyridine. Attempted extension of the general indolizine route to the preparation of chromene systems by reacting salicylaldehyde with methyl acrylate in the presence of DABCO, also led to an unexpected, crystalline material, identified by single crystal X-ray diffraction analysis as the coumarin derivative, 3-[(2-formylphenoxy)methyl]coumarin.A series of chloroquine analogues have been prepared from indolizine-2-carboxylic acid, pyrrolo[I,2-a]quinoline-2-carboxylic acid and imidazo[I,2-a]pyridine-2-carboxylic acid by reaction with suitable amines in the presence of the coupling reagent 1, I' -carbonyldiimidazole. This route has been shown to be a vast improvement on earlier procedures and has provided access to both secondary and tertiary indolizine-2-carboxamides. A range of N,N-dialkylindolizine-2-carboxamides have been prepared by this route, and the influence of substituents on their N-CO rotational energy barriers has been determined using variable temperature ¹H and ¹³C NMR techniques. Intercalation with natural DNA by both chloroquine and the synthesized chloroquine analogues has been examined using UV spectrophotometry, and ¹H and ³¹P NMR spectroscopy. The pyrrolo[I,2-a]quinolines have been shown to be DNA intercalators with binding affinities similar to that of the known antimalarial intercalator, chloroquine. In a preliminary study the synthesis of a short oligonucleotide has been undertaken and changes have been observed in the ¹H and ³¹P NMR spectra of the oligonucleotide on addition of the intercalator, chloroquine.
- Full Text:
- Date Issued: 1994
The thermodynamics of solutions and binary liquid mixtures
- Authors: Mercer-Chalmers, June Dawn
- Date: 1993
- Subjects: Thermodynamics Liquids Solution (Chemistry)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4390 , http://hdl.handle.net/10962/d1005055
- Description: The thesis is presented in two parts. In part one, the excess thermodynamic properties have been determined for several binary liquid mixtures, with the aim of testing theories of liquid mixtures. The excess molar enthalpies, Hem, have been determined using an LKB flow microcalorimeter, and the excess molar volumes, Vem, have been determined using an Anton Paar densitometer. The HemS and VemS have been measured at 298.15 K for binary systems involving an alkanol (methanol, ethanol, I-propanol, 2-propanol) mixed with a hydrocarbon (l-hexene, I-heptene, l-octene, I-hexyne, I-heptyne, l-octyne, toluene, mesitylene, 0-, m-, or p-xylene, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclodecane). The results show trends relating to the degree of unsaturation, or size, of component molecules as well as the position of the hydroxyl group on the alkanol. Measurements were also made on mixtures involving an (n-alkane + a pseudo-n-alkane) and ( a cYcloalkane + a pseudo-cycloalkane). Two theories of liquid mixtures were tested in this work. The first theory tested was the theory of Congruency. This theory was tested, by means of a null test, on a novel set of mixtures involving an n-alkane (hexane, heptane, octane, decane, dodecane) + a pseudo-nalkane,and mixtures of a cycloalkane (cyclopentane, cyclohexane, cycloheptane, cyclooctane)+ a pseudo-cycloalkane. Deviations from the theory was less than the experimental error for the (n-alkane + pseudo-n-alkane) mixtures. However, significant deviations were observed for the mixtures of (a cycloalkane + a pseudo-cycloalkane). The second theory tested was the Flory theory, which has been used to predict the excess molar enthalpies and excess molar volumes for the mixtures involving (a 1-alkene, or 1-alkyne, or methyl-substituted benzene) + an alkanol. The results show that the theory does not hold for hydrocarbon mixtures involving an alkanol. In the second part of this thesis, the partial molar volumes, at infinite dilution, of binary solution involving a solid solute (18-crown-6 ether, dibenzo-18-crown-6 ether, dicyclohexanov 18-crown-6 ether, 15-crown-5 ether, or cryptand-222) are determined in various solvents. The results were repeated with a view to determine the volume changes at infinite dilution upon complexation, ΔV∞ of the crown ether or cryptand with a metal halide salt, MX (NaCl, NaI, KCl, KI, CsCl, CsI). The ΔV∞ results were compared with results in the literature for cryptand-222 (c-222) and dibenzo-18-crown-6 ether (B₂CE6) complexed with MX, and the study was extended to include further MX complexes with c-222 and B₂CE6, as well as MX complexes with 15-crown-5 ether and dicyclohexano-18-crown-6 ether. ΔV∞ results were correlated with the Hepler prediction of the electrostriction solvent effect.
- Full Text:
- Date Issued: 1993
- Authors: Mercer-Chalmers, June Dawn
- Date: 1993
- Subjects: Thermodynamics Liquids Solution (Chemistry)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4390 , http://hdl.handle.net/10962/d1005055
- Description: The thesis is presented in two parts. In part one, the excess thermodynamic properties have been determined for several binary liquid mixtures, with the aim of testing theories of liquid mixtures. The excess molar enthalpies, Hem, have been determined using an LKB flow microcalorimeter, and the excess molar volumes, Vem, have been determined using an Anton Paar densitometer. The HemS and VemS have been measured at 298.15 K for binary systems involving an alkanol (methanol, ethanol, I-propanol, 2-propanol) mixed with a hydrocarbon (l-hexene, I-heptene, l-octene, I-hexyne, I-heptyne, l-octyne, toluene, mesitylene, 0-, m-, or p-xylene, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclodecane). The results show trends relating to the degree of unsaturation, or size, of component molecules as well as the position of the hydroxyl group on the alkanol. Measurements were also made on mixtures involving an (n-alkane + a pseudo-n-alkane) and ( a cYcloalkane + a pseudo-cycloalkane). Two theories of liquid mixtures were tested in this work. The first theory tested was the theory of Congruency. This theory was tested, by means of a null test, on a novel set of mixtures involving an n-alkane (hexane, heptane, octane, decane, dodecane) + a pseudo-nalkane,and mixtures of a cycloalkane (cyclopentane, cyclohexane, cycloheptane, cyclooctane)+ a pseudo-cycloalkane. Deviations from the theory was less than the experimental error for the (n-alkane + pseudo-n-alkane) mixtures. However, significant deviations were observed for the mixtures of (a cycloalkane + a pseudo-cycloalkane). The second theory tested was the Flory theory, which has been used to predict the excess molar enthalpies and excess molar volumes for the mixtures involving (a 1-alkene, or 1-alkyne, or methyl-substituted benzene) + an alkanol. The results show that the theory does not hold for hydrocarbon mixtures involving an alkanol. In the second part of this thesis, the partial molar volumes, at infinite dilution, of binary solution involving a solid solute (18-crown-6 ether, dibenzo-18-crown-6 ether, dicyclohexanov 18-crown-6 ether, 15-crown-5 ether, or cryptand-222) are determined in various solvents. The results were repeated with a view to determine the volume changes at infinite dilution upon complexation, ΔV∞ of the crown ether or cryptand with a metal halide salt, MX (NaCl, NaI, KCl, KI, CsCl, CsI). The ΔV∞ results were compared with results in the literature for cryptand-222 (c-222) and dibenzo-18-crown-6 ether (B₂CE6) complexed with MX, and the study was extended to include further MX complexes with c-222 and B₂CE6, as well as MX complexes with 15-crown-5 ether and dicyclohexano-18-crown-6 ether. ΔV∞ results were correlated with the Hepler prediction of the electrostriction solvent effect.
- Full Text:
- Date Issued: 1993
Chemical and spectroscopic studies of chromone derivatives
- Authors: Davidson, Deborah Nicole
- Date: 1992
- Subjects: Chromatophores Plant pigments Asthma -- Treatment -- Research
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4420 , http://hdl.handle.net/10962/d1006857
- Description: Various chromone derivatives have been used in asthma therapy, and their biological activity is apparently related to certain chemical features which include conformation and acidity. In the present study, substituent effects on conformation and acidity have been explored in chromone systems with potential biological activity. A range of variously substituted symmetrical chromone-2-carboxamides (including a series of N,N-dimethylchromone-2-carboxamides) have been prepared via chromone-2-carboxylic acids, which, in turn, were prepared from the corresponding o-hydroxyacetophenones. The N,N-dimethylchromone-2-carboxamides were prepared by reacting the appropriate chromone-2-carbonyl chlorides with dimethylammonium chloride in pyridine, in an approach which resolved various problems encountered in the preparation of these compounds. Substituent effects on the conformation of chromone-2-carboxamides have been explored using dynamic NMR spectroscopy, and the observed splitting of the N-alkyl signals has been attributed to slow site-exchange of the N-alkyl substituents. Dynamic NMR frequency separations and coalescence temperatures have been used to calculate rotational energy barriers, and substituent effects on these rotational energy barriers have been analysed. The possible implication of ring-opening of chromones in chromone pharmacology has also been examined. A range of 3-(2-hydroxybenzoyl)acrylamides has been prepared via the dimethylamine-mediated ring-opening of N,N-dimethylchromone-2-carboxamides and the E-double-bond configuration of the ring-opened products has been unambiguously established by single crystal analysis of the parent system. The configuration and conformation of the crystal structure of the parent system have been shown, using IR and NMR spectroscopic, and molecular graphics techniques, to be maintained in solution and to characterise the whole series. ¹H and ¹³C NMR spectroscopy have also been used to study the dimethylamine-mediated ring-opening of disodium cromoglycate. The kinetics of the dimethylamine-mediated ring-opening of N,N-dimethylchromone-2-carboxamides have been studied using UV spectroscopy. These reactions have been shown to follow third-order kinetics overall and a mechanism accommodating the observed third-order kinetics has been proposed. Substituent effects have been further investigated by the potentiometric determination of the pKa (pK [subscript a]) values for a series of chromone-2-carboxylic acids. The relationship between acidity and the observed rate constants has been explored and has verified that the observed rate constants are sensitive to the influence of meta-substituents on the stability of the phenoxide ion "leaving group" rather than C-2 electrophilicity.
- Full Text:
- Date Issued: 1992
- Authors: Davidson, Deborah Nicole
- Date: 1992
- Subjects: Chromatophores Plant pigments Asthma -- Treatment -- Research
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4420 , http://hdl.handle.net/10962/d1006857
- Description: Various chromone derivatives have been used in asthma therapy, and their biological activity is apparently related to certain chemical features which include conformation and acidity. In the present study, substituent effects on conformation and acidity have been explored in chromone systems with potential biological activity. A range of variously substituted symmetrical chromone-2-carboxamides (including a series of N,N-dimethylchromone-2-carboxamides) have been prepared via chromone-2-carboxylic acids, which, in turn, were prepared from the corresponding o-hydroxyacetophenones. The N,N-dimethylchromone-2-carboxamides were prepared by reacting the appropriate chromone-2-carbonyl chlorides with dimethylammonium chloride in pyridine, in an approach which resolved various problems encountered in the preparation of these compounds. Substituent effects on the conformation of chromone-2-carboxamides have been explored using dynamic NMR spectroscopy, and the observed splitting of the N-alkyl signals has been attributed to slow site-exchange of the N-alkyl substituents. Dynamic NMR frequency separations and coalescence temperatures have been used to calculate rotational energy barriers, and substituent effects on these rotational energy barriers have been analysed. The possible implication of ring-opening of chromones in chromone pharmacology has also been examined. A range of 3-(2-hydroxybenzoyl)acrylamides has been prepared via the dimethylamine-mediated ring-opening of N,N-dimethylchromone-2-carboxamides and the E-double-bond configuration of the ring-opened products has been unambiguously established by single crystal analysis of the parent system. The configuration and conformation of the crystal structure of the parent system have been shown, using IR and NMR spectroscopic, and molecular graphics techniques, to be maintained in solution and to characterise the whole series. ¹H and ¹³C NMR spectroscopy have also been used to study the dimethylamine-mediated ring-opening of disodium cromoglycate. The kinetics of the dimethylamine-mediated ring-opening of N,N-dimethylchromone-2-carboxamides have been studied using UV spectroscopy. These reactions have been shown to follow third-order kinetics overall and a mechanism accommodating the observed third-order kinetics has been proposed. Substituent effects have been further investigated by the potentiometric determination of the pKa (pK [subscript a]) values for a series of chromone-2-carboxylic acids. The relationship between acidity and the observed rate constants has been explored and has verified that the observed rate constants are sensitive to the influence of meta-substituents on the stability of the phenoxide ion "leaving group" rather than C-2 electrophilicity.
- Full Text:
- Date Issued: 1992
Interaction of selected fungicides with insoluble bovine skin collagen in the presence of the non ionic surfactant Triton X-100
- Authors: Fowler, William Mackenzie
- Date: 1992
- Subjects: Collagenases -- Research Fungicides -- Research Hides and skins -- Preservation
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4318 , http://hdl.handle.net/10962/d1004976
- Description: In the leather industry fungicides are often used for the protection of wet-blue leather. These fungicides are usually only sparingly soluble and are therefore formulated together with surfactants in order to increase their solubility and to ensure an even distribution over the surface of the hide after treatment. Solutions containing both fungicides and surfactant are complex. The nature of these solutions was investigated. By means of UV/Vis spectroscopy and viscometry it was shown that the surfactant and fungicides form micelles and mixed micelles in solution. The nature of these micelles and mixed micelles was dependent on the solution temperature as well as on the concentrations of the surfactant and fungicides. At the higher temperatures and concentrations transition to large, possibly rod-shaped, mixed micelles occurred. The interaction between the selected fungicides 2-(thiocyanomethylthio)benzothiazole and n-octyl-4-isothiazol-3-one with bovine skin collagen in the form of both limed and lightly chromed hide powder in the presence of the non ionic surfactant Triton X -100 was investigated. Fungicide uptake was determined by difference measurements on the float solutions at regular intervals during treatment. Binding was rapid with equilibrium being established within the first six hours even for the solutions with the highest surfactant concentration. Binding failed to follow a normal mass-action binding-type isotherm approaching a saturation limit, but increased continuously indicating a co-operative effect whereby binding site affinity actually increased with the amount of ligand bound. Binding was accompanied by a drop in the free surfactant in the solution at the higher biocide levels indicating the formation of complex mixed micelles which bind to the collagen fibres. The uptake and antifungal activity of commercial fomulations of the fungicides on chrome-tanned wet-blue leather was investigated at various treatment temperatures. At lower fungicide treatment concentrations, binding tended to follow a typical mass-action type binding isotherm, increasing slightly with temperature. At higher float concentrations, an inflexion point was apparent beyond which uptake showed a marked increase with concentration. This inflexion point, signifying a change in binding characteristics, occurred at progressively lower concentrations with increasing temperature. Antifungal activity in terms of storage periods to onset of fungal growth was determined on the wet-blue leather cuttings immediately after treatment and drainage and also on sample discs after exhaustive extraction of free fungicide using dichloromethane. Storage performance testing of the various treated wet-blue leathers was carried out by different methods. Residual protective periods showed a curvilinear increase with dosage offer and surface uptake. In the low dosage range treatment temperature had only a relatively slight effect in promoting uptake and improving storage protection. At higher dosages, the influence of temperature on uptake and storage protection was greater due to the increase in surface binding of the fungicides at the elevated temperatures. Only a portion of the fungicide uptake was recovered by direct solvent extraction of the treated wet-blue leather. Solvent extraction reduced storage margins. The storage response in relation to fungicide content was, however comparable after extraction, indicating that both irreversibly bound and physically associated fungicide offered effective protection. Results of the study provide further insight into the mode of interaction of fungicide emulsion dispersion with bovine skin collagen, and the importance of the emulsion dispersions and its stability in determining the uptake of fungicide.
- Full Text:
- Date Issued: 1992
- Authors: Fowler, William Mackenzie
- Date: 1992
- Subjects: Collagenases -- Research Fungicides -- Research Hides and skins -- Preservation
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4318 , http://hdl.handle.net/10962/d1004976
- Description: In the leather industry fungicides are often used for the protection of wet-blue leather. These fungicides are usually only sparingly soluble and are therefore formulated together with surfactants in order to increase their solubility and to ensure an even distribution over the surface of the hide after treatment. Solutions containing both fungicides and surfactant are complex. The nature of these solutions was investigated. By means of UV/Vis spectroscopy and viscometry it was shown that the surfactant and fungicides form micelles and mixed micelles in solution. The nature of these micelles and mixed micelles was dependent on the solution temperature as well as on the concentrations of the surfactant and fungicides. At the higher temperatures and concentrations transition to large, possibly rod-shaped, mixed micelles occurred. The interaction between the selected fungicides 2-(thiocyanomethylthio)benzothiazole and n-octyl-4-isothiazol-3-one with bovine skin collagen in the form of both limed and lightly chromed hide powder in the presence of the non ionic surfactant Triton X -100 was investigated. Fungicide uptake was determined by difference measurements on the float solutions at regular intervals during treatment. Binding was rapid with equilibrium being established within the first six hours even for the solutions with the highest surfactant concentration. Binding failed to follow a normal mass-action binding-type isotherm approaching a saturation limit, but increased continuously indicating a co-operative effect whereby binding site affinity actually increased with the amount of ligand bound. Binding was accompanied by a drop in the free surfactant in the solution at the higher biocide levels indicating the formation of complex mixed micelles which bind to the collagen fibres. The uptake and antifungal activity of commercial fomulations of the fungicides on chrome-tanned wet-blue leather was investigated at various treatment temperatures. At lower fungicide treatment concentrations, binding tended to follow a typical mass-action type binding isotherm, increasing slightly with temperature. At higher float concentrations, an inflexion point was apparent beyond which uptake showed a marked increase with concentration. This inflexion point, signifying a change in binding characteristics, occurred at progressively lower concentrations with increasing temperature. Antifungal activity in terms of storage periods to onset of fungal growth was determined on the wet-blue leather cuttings immediately after treatment and drainage and also on sample discs after exhaustive extraction of free fungicide using dichloromethane. Storage performance testing of the various treated wet-blue leathers was carried out by different methods. Residual protective periods showed a curvilinear increase with dosage offer and surface uptake. In the low dosage range treatment temperature had only a relatively slight effect in promoting uptake and improving storage protection. At higher dosages, the influence of temperature on uptake and storage protection was greater due to the increase in surface binding of the fungicides at the elevated temperatures. Only a portion of the fungicide uptake was recovered by direct solvent extraction of the treated wet-blue leather. Solvent extraction reduced storage margins. The storage response in relation to fungicide content was, however comparable after extraction, indicating that both irreversibly bound and physically associated fungicide offered effective protection. Results of the study provide further insight into the mode of interaction of fungicide emulsion dispersion with bovine skin collagen, and the importance of the emulsion dispersions and its stability in determining the uptake of fungicide.
- Full Text:
- Date Issued: 1992
Intersolid pyrotechnic reactions of silicon
- Authors: Rugunanan, Rajan Anil
- Date: 1992
- Subjects: Thermochemistry , Thermal analysis , Chemistry, Analytic , Chemistry, Organic , Silicon
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4527 , http://hdl.handle.net/10962/d1015571
- Description: A study of the role of different oxidants with silicon as the fuel in simple binary pyrotechnic compositions is reported. Several oxidants were examined, but only three (Sb₂0₃, Fe₂0₃ and Sn0₂) satisfied the restrictions that the combustion temperatures should be below the melting point of platinum/rhodium thermocouples (1760°C), that burning rates should not exceed the response of the thermocouples, and that burning should occur without significant mass-transport. A fourth oxidant, KN0₃, was selected on account of its low melting point and general importance as a pyrotechnic oxidant. The oxidation of silicon in the presence of either Sb₂0₃ or KN0₃ could be identified from thermal analysis curves. No thermal events were noted when Si/Sn0₂ and SiFe₂0₃ compositions were heated under similar conditions. The oxidation of Si powder in oxygen was also studied. All four binary systems sustained burning over a reasonably wide range of compositions. The range of burning rates measured (2 to 35 mm s⁻¹) depended on the oxidant used. Fe₂0₃ and Sb₂0₃ gave slow burning mixtures compared to Sn0₂ and to KN0₃ compositions with a high Si content. Burning rates generally increased with increasing specific surface area of silicon, but decreased in the presence of inert diluents and moisture. The burning rates of the Si/Fe₂0₃ and Si/Sn0₂ systems increased with increasing compaction of the samples. Kinetic parameters derived from the temperature proftles recorded during combustion were generally low (6 to 37 kJ mol⁻¹). This is in keeping with proposals that burning is diffusion controlled. The values of kinetic parameters derived from thermal analysis curves were considerably greater ( > 250 kJ mol⁻¹). Two other fuels, FeSi₇ and CaSi₂, gave similar thermal analysis curves when used instead of silicon. There were considerable differences in the burning rates for binary mixtures of these fuels compared to silicon. Ternary systems with two fuels or two oxidants showed that only limited interaction occurs during thermal analysis. The use of a second fuel or oxidant did, however, modify the burning behaviour considerably. Other techniques used in this study to probe the details of the reaction processes included bomb calorimetry, measurement of thermal conductivities, infrared spectroscopy, X-ray diffraction and scanning electron micoscropy.
- Full Text:
- Date Issued: 1992
- Authors: Rugunanan, Rajan Anil
- Date: 1992
- Subjects: Thermochemistry , Thermal analysis , Chemistry, Analytic , Chemistry, Organic , Silicon
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4527 , http://hdl.handle.net/10962/d1015571
- Description: A study of the role of different oxidants with silicon as the fuel in simple binary pyrotechnic compositions is reported. Several oxidants were examined, but only three (Sb₂0₃, Fe₂0₃ and Sn0₂) satisfied the restrictions that the combustion temperatures should be below the melting point of platinum/rhodium thermocouples (1760°C), that burning rates should not exceed the response of the thermocouples, and that burning should occur without significant mass-transport. A fourth oxidant, KN0₃, was selected on account of its low melting point and general importance as a pyrotechnic oxidant. The oxidation of silicon in the presence of either Sb₂0₃ or KN0₃ could be identified from thermal analysis curves. No thermal events were noted when Si/Sn0₂ and SiFe₂0₃ compositions were heated under similar conditions. The oxidation of Si powder in oxygen was also studied. All four binary systems sustained burning over a reasonably wide range of compositions. The range of burning rates measured (2 to 35 mm s⁻¹) depended on the oxidant used. Fe₂0₃ and Sb₂0₃ gave slow burning mixtures compared to Sn0₂ and to KN0₃ compositions with a high Si content. Burning rates generally increased with increasing specific surface area of silicon, but decreased in the presence of inert diluents and moisture. The burning rates of the Si/Fe₂0₃ and Si/Sn0₂ systems increased with increasing compaction of the samples. Kinetic parameters derived from the temperature proftles recorded during combustion were generally low (6 to 37 kJ mol⁻¹). This is in keeping with proposals that burning is diffusion controlled. The values of kinetic parameters derived from thermal analysis curves were considerably greater ( > 250 kJ mol⁻¹). Two other fuels, FeSi₇ and CaSi₂, gave similar thermal analysis curves when used instead of silicon. There were considerable differences in the burning rates for binary mixtures of these fuels compared to silicon. Ternary systems with two fuels or two oxidants showed that only limited interaction occurs during thermal analysis. The use of a second fuel or oxidant did, however, modify the burning behaviour considerably. Other techniques used in this study to probe the details of the reaction processes included bomb calorimetry, measurement of thermal conductivities, infrared spectroscopy, X-ray diffraction and scanning electron micoscropy.
- Full Text:
- Date Issued: 1992
Binary and ternary pyrotechnic systems containing manganese, molybdenum, barium peroxide and strontium peroxide
- Authors: Drennan, Robin Lennox
- Date: 1991
- Subjects: Thermochemistry -- Research Thermal analysis -- Research Chemistry, Analytic -- Research Manganese Molybdenum
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4411 , http://hdl.handle.net/10962/d1006765
- Description: Barium peroxide was selected as oxidant in a fundamental physico-chemical study of binary pyrotechnic systems on account of its apparently simple decomposition stoichiometry. With this selection, the choice of fuel was governed by the requirements of a self-sustaining reaction at combustion temperatures below the melting point of the platinum/rhodium thermocouples (∼1760°C) used for recording temperature-time profiles during burning, and at burning rates not exceeding the response of the sensors used to monitor combustion. Both manganese and molybdenum metal powders satisfied the above requirements. Strontium peroxide was also available as an oxidant and so the combustion of binary metal/oxidant systems using both fuels and both BaO₂ and SrO₂ oxidants was investigated. The Mn/BaO₂, MoBaO₂ and Mn/SrO₂ systems burnt over a wide range of compositions, but the range of ignitable compositions for the Mo/SrO₂ system was very limited. The linear burning rates, for all these systems, ranged from 2 to 12 mm s⁻¹ and burning rates were increased by the use of smaller particle-sizes of fuel and greater loading pressures. Inert additives generally decreased the burning rate. Temperature-time profiles were recorded for all the compositions which sustained combustion. Kinetic parameters were estimated from the shapes of these profiles using procedures developed by Hill et al and Boddington and Laye. Activation energies derived from the profiles were low (3 to 40 kJ mol⁻¹) and support suggestions that reactions at high temperatures are controlled by diffusion processes. Thermal analysis was used to identify the processes occurring in the four systems. The main exothermic events were observed to correspond approximately with the onset of oxidant decomposition. A pre-ignition reaction was tentatively identified in the Mn/BaO₂ system. Oxidation of the metal fuels was generally incomplete, probably because of the formation of protective layers of product. Activation energies, derived from thermal analysis results, were in the range of from 70 to 720 kJ mol⁻¹. Ternary systems containing either mixed fuels or mixed oxidants were also examined. No interactions hetween the fuels or between the oxidants were observed. Other techniques used included bomb calorimetry, measurement of thermal conductivity, X-ray powder diffraction, infrared spectroscopy and scanning electron microscopy.
- Full Text:
- Date Issued: 1991
- Authors: Drennan, Robin Lennox
- Date: 1991
- Subjects: Thermochemistry -- Research Thermal analysis -- Research Chemistry, Analytic -- Research Manganese Molybdenum
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4411 , http://hdl.handle.net/10962/d1006765
- Description: Barium peroxide was selected as oxidant in a fundamental physico-chemical study of binary pyrotechnic systems on account of its apparently simple decomposition stoichiometry. With this selection, the choice of fuel was governed by the requirements of a self-sustaining reaction at combustion temperatures below the melting point of the platinum/rhodium thermocouples (∼1760°C) used for recording temperature-time profiles during burning, and at burning rates not exceeding the response of the sensors used to monitor combustion. Both manganese and molybdenum metal powders satisfied the above requirements. Strontium peroxide was also available as an oxidant and so the combustion of binary metal/oxidant systems using both fuels and both BaO₂ and SrO₂ oxidants was investigated. The Mn/BaO₂, MoBaO₂ and Mn/SrO₂ systems burnt over a wide range of compositions, but the range of ignitable compositions for the Mo/SrO₂ system was very limited. The linear burning rates, for all these systems, ranged from 2 to 12 mm s⁻¹ and burning rates were increased by the use of smaller particle-sizes of fuel and greater loading pressures. Inert additives generally decreased the burning rate. Temperature-time profiles were recorded for all the compositions which sustained combustion. Kinetic parameters were estimated from the shapes of these profiles using procedures developed by Hill et al and Boddington and Laye. Activation energies derived from the profiles were low (3 to 40 kJ mol⁻¹) and support suggestions that reactions at high temperatures are controlled by diffusion processes. Thermal analysis was used to identify the processes occurring in the four systems. The main exothermic events were observed to correspond approximately with the onset of oxidant decomposition. A pre-ignition reaction was tentatively identified in the Mn/BaO₂ system. Oxidation of the metal fuels was generally incomplete, probably because of the formation of protective layers of product. Activation energies, derived from thermal analysis results, were in the range of from 70 to 720 kJ mol⁻¹. Ternary systems containing either mixed fuels or mixed oxidants were also examined. No interactions hetween the fuels or between the oxidants were observed. Other techniques used included bomb calorimetry, measurement of thermal conductivity, X-ray powder diffraction, infrared spectroscopy and scanning electron microscopy.
- Full Text:
- Date Issued: 1991
Studies in asymmetric synthesis
- Authors: Learmonth, Robin Alec
- Date: 1991
- Subjects: Organic compounds -- Synthesis Stereochemistry Organosilicon compounds Chirality Chemical tests and reagents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4353 , http://hdl.handle.net/10962/d1005018
- Description: The concept of combining two well established areas of organic chemistry, viz., organosilicon chemistry and the use of chiral auxiliaries, into a viable, alternative method of asymmetric synthesis has only very recently begun to receive attention. At the outset of this investigation, no asymmetric reactions of silyl enol ethers, chiral by virtue of optically active substituents on the silicon, had been reported. A range of novel chiral silyl enol ethers have thus been prepared from a variety of ketones, including pinacolone, cyclohexanone, and α-tetralone, and employing menthol, borneol, and cholesterol as chiral auxiliaries. These preparations have been achieved via several distinct routes, including a novel convergent approach involving the isolation of either the chloro(menthyloxy)dimethylsilane or the (bornyloxy)chlorodimethylsilane. The MS and NMR spectra of these silyl enol ethers were examined in detail and, in the case of the crystalline cholesteryloxy silyl enol ether, the X-ray structure has been determined. The potential of chloroalkoxysilanes to act as general, chiral derivatizing agents has been established by the preparation of diastereomeric silyl acetal mixtures of racemic secondary alcohols (e.g. I-phenylethanol and 2-octanol). The experimental diastereomeric ratios, obtained by GLC and ¹H NMR spectroscopy, approached the expected value of unity, confirming the potential of the alkoxychlorosilanes as chiral probes. The chiral silyl enol ethers have been successfully oxidized to the corresponding α-siloxy ketones employing MCPBA, MMPP, and 2-(phenylsulphonyl)-3-phenyloxaziridine as oxidizing agents and the diastereomeric excesses obtained, which varied from 0 to 16%, indicated some potential for stereochemical control. Alkylation and hydroxyalkylation reactions of the silyl enol ethers have yielded the expected α-iert-butyl and β-hydroxy ketones in good to excellent material yields, with the enantiomeric excesses, as determined by chiral shift reagent studies, reaching 14%. To improve the stereo control in these reactions, attempts have been made to prepare chiral silyl enol ethers with auxiliaries possessing the potential for transition state complex co-ordination in the reactions under consideration. The preparation of such silyl enol ethers, incorporating the proline-derived auxiliaries, N-methyl-2-hydroxymethylpyrrolidine and 2-methoxymethylpyrrolidine met with only limited success. In an alternative approach, three derivatives of 2,3-dihydroxybornane have been prepared. However, two of these auxiliaries, viz., 3-exo-benzyloxy-2-exo-hydroxybornane and 3-exo-(1-methoxyethoxy)-2-exo-hydroxybornane failed to form silyl enol ethers, even under considerably more vigorous conditions than normally employed. The third derivative, 3,3-ethylenedioxy-2-hydroxybornane has been successfully utilized in the preparation of a pinacolone-derived chiral silyl enol ether. Hydroxyalkylation of this compound with benzaldehyde has yielded the β-hydroxyketone with significantly improved enantiomeric excess (26%) and a transition state complex has been proposed to rationalize this improvement.
- Full Text:
- Date Issued: 1991
- Authors: Learmonth, Robin Alec
- Date: 1991
- Subjects: Organic compounds -- Synthesis Stereochemistry Organosilicon compounds Chirality Chemical tests and reagents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4353 , http://hdl.handle.net/10962/d1005018
- Description: The concept of combining two well established areas of organic chemistry, viz., organosilicon chemistry and the use of chiral auxiliaries, into a viable, alternative method of asymmetric synthesis has only very recently begun to receive attention. At the outset of this investigation, no asymmetric reactions of silyl enol ethers, chiral by virtue of optically active substituents on the silicon, had been reported. A range of novel chiral silyl enol ethers have thus been prepared from a variety of ketones, including pinacolone, cyclohexanone, and α-tetralone, and employing menthol, borneol, and cholesterol as chiral auxiliaries. These preparations have been achieved via several distinct routes, including a novel convergent approach involving the isolation of either the chloro(menthyloxy)dimethylsilane or the (bornyloxy)chlorodimethylsilane. The MS and NMR spectra of these silyl enol ethers were examined in detail and, in the case of the crystalline cholesteryloxy silyl enol ether, the X-ray structure has been determined. The potential of chloroalkoxysilanes to act as general, chiral derivatizing agents has been established by the preparation of diastereomeric silyl acetal mixtures of racemic secondary alcohols (e.g. I-phenylethanol and 2-octanol). The experimental diastereomeric ratios, obtained by GLC and ¹H NMR spectroscopy, approached the expected value of unity, confirming the potential of the alkoxychlorosilanes as chiral probes. The chiral silyl enol ethers have been successfully oxidized to the corresponding α-siloxy ketones employing MCPBA, MMPP, and 2-(phenylsulphonyl)-3-phenyloxaziridine as oxidizing agents and the diastereomeric excesses obtained, which varied from 0 to 16%, indicated some potential for stereochemical control. Alkylation and hydroxyalkylation reactions of the silyl enol ethers have yielded the expected α-iert-butyl and β-hydroxy ketones in good to excellent material yields, with the enantiomeric excesses, as determined by chiral shift reagent studies, reaching 14%. To improve the stereo control in these reactions, attempts have been made to prepare chiral silyl enol ethers with auxiliaries possessing the potential for transition state complex co-ordination in the reactions under consideration. The preparation of such silyl enol ethers, incorporating the proline-derived auxiliaries, N-methyl-2-hydroxymethylpyrrolidine and 2-methoxymethylpyrrolidine met with only limited success. In an alternative approach, three derivatives of 2,3-dihydroxybornane have been prepared. However, two of these auxiliaries, viz., 3-exo-benzyloxy-2-exo-hydroxybornane and 3-exo-(1-methoxyethoxy)-2-exo-hydroxybornane failed to form silyl enol ethers, even under considerably more vigorous conditions than normally employed. The third derivative, 3,3-ethylenedioxy-2-hydroxybornane has been successfully utilized in the preparation of a pinacolone-derived chiral silyl enol ether. Hydroxyalkylation of this compound with benzaldehyde has yielded the β-hydroxyketone with significantly improved enantiomeric excess (26%) and a transition state complex has been proposed to rationalize this improvement.
- Full Text:
- Date Issued: 1991
Essential fatty acids and ascorbic acid- interactions and effects on melanoma growth
- Authors: Gardiner, Neil Stockenstrom
- Date: 1990
- Subjects: Fatty acids , Melanoma , Mice -- Diseases
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4549 , http://hdl.handle.net/10962/d1018230
- Description: The present study was carried out to determine the effects and possible mechanisms of action of the essential fatty acids (EFAs) (linoleic acid (LA), gamma-linolenic acid (GLA) and arachidonic acid (AA)) and ascorbic acid (Asc) on BL6 murine melanoma growth in cell culture and in mice. Interactions between the nutrients in influencing melanoma growth as well as possible mechanisms of the interactions were also examined in the above systems. Cell culture studies revealed that all three EFAs (0-SOμg/ml) and Asc (0-200μg/ml) significantly inhibited melanoma growth at the concentrations used. The EF As were also found to significantly inhibit growth, although to a lesser extent than BL6 cells, of monkey kidney (LLCMK) cells which were used as a non-malignant control cell line. Asc in contrast was found not to inhibit growth of these cells. Supplementation of Asc (lOO)μg/ml) to EFA containing (0-50μg/ml) medium was found to significantly increase inhibition of cell growth in both cell lines, and in the BL6 cells in particular, after taking into account the growth inhibitory effects of Asc in the absence of EFAs. The mechanism of cell growth inhibition by the EF As appeared to involve lipid peroxidation but not enhanced prostaglandin (PG) or leukotriene (LT) synthesis. While Asc was found to increase both lipid peroxidation and PG synthesis in the cells, these mechanisms and enhanced LT synthesis did not appear to have played a role in the inhibition of cell growth by Asc or in the growth inhibitory interaction between Asc and the EF As. In vivo studies revealed that diets containing essential or polyunsaturated fatty acids (EFAs/PUFAs) in the form of vegetable oils, and in particular GLA in the form of evening primrose oil, significantly promoted melanoma growth in mice when compared with an EFA/PUFA free diet containing predominantly saturated fats (SF). Supplementary dietary Asc in contrast was found to significantly inhibit melanoma growth in mice fed EFA/PUFA, and in particular GLA, containing diets but not in mice fed SF cont~g diets. This result appears to indicate the occurrence of an interaction between the two nutrients. Ul The mechanism of tumour promotion by the EP As/PUP As did not appear to have involved enhanced PG or LT synthesis or lipid peroxidation. Since dietary EPA/PUPA manipulation was found to significantly alter the EPA content of tissues, including the melanomas, the mechanism of tumour promotion may have involved changes in the EPA composition of the tumour cells. While supplementary Asc was found to significantly increase the Asc content of certain tissues, including the melanomas, which may have played a role in tumour growth inhibition by Asc, it was found not to affect the EPA content of tissues. Enhanced PG or LT synthesis and lipid perox:idation did not appear to have been involved in the tumour growth inhibitory interaction between Asc and the EP As/PUP As. THe activity of the enzyme delta-6-desaturase, a key enzyme in EF A metabolism which catalyses the desaturation of LA to GLA, and the influence of Asc on activity of the enzyme were also examined. The cultured cells, and BL6 cells in particular, were found to contain significant activity of the enzyme. Whereas murine liver microsomal fractions were found to contain delta-6-desaturase activity, microsomes from melanomas grown in mice were found to lack activity of the enzyme. The significant tumour promoting effects of the GLA containing EPO diet may have been the result of the lack of delta-6-desaturase activity in tumour cells grown in mice. Asc was found to stimulate activity of the enzyme in cultured BL6 cells but not in LLCM.K cells, while dietary Asc and EF A/PUP A manipulation did not influence activity of the enzyme in microsomal fractions. This study has confirmed previous reports of the in vivo tumour promoting effects of dietary EP As/PUP As and the tumour growth inhibitory effects of Asc. The in vitro cell growth inhibitory effects of Asc and the EP As also confirm the results of previous reports. Previous studies investigating possible interactions between Asc and EP As/PUP As in influencing tumour cell growth could not be located in the relevant literature. This study may therefore be one of the first investigations of any such interaction between these nutrients in tumour cells. While this study was not able to identify the mechanisms involved in the different tumour promoting or tumour growth inhibitory effects of the two nutrients in the two systems, it did eliminate a number of potential mechanisms. The results of this study also emphasise the difficulty of attempting to compare the results of in vitro and in vivo studies.
- Full Text:
- Date Issued: 1990
- Authors: Gardiner, Neil Stockenstrom
- Date: 1990
- Subjects: Fatty acids , Melanoma , Mice -- Diseases
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4549 , http://hdl.handle.net/10962/d1018230
- Description: The present study was carried out to determine the effects and possible mechanisms of action of the essential fatty acids (EFAs) (linoleic acid (LA), gamma-linolenic acid (GLA) and arachidonic acid (AA)) and ascorbic acid (Asc) on BL6 murine melanoma growth in cell culture and in mice. Interactions between the nutrients in influencing melanoma growth as well as possible mechanisms of the interactions were also examined in the above systems. Cell culture studies revealed that all three EFAs (0-SOμg/ml) and Asc (0-200μg/ml) significantly inhibited melanoma growth at the concentrations used. The EF As were also found to significantly inhibit growth, although to a lesser extent than BL6 cells, of monkey kidney (LLCMK) cells which were used as a non-malignant control cell line. Asc in contrast was found not to inhibit growth of these cells. Supplementation of Asc (lOO)μg/ml) to EFA containing (0-50μg/ml) medium was found to significantly increase inhibition of cell growth in both cell lines, and in the BL6 cells in particular, after taking into account the growth inhibitory effects of Asc in the absence of EFAs. The mechanism of cell growth inhibition by the EF As appeared to involve lipid peroxidation but not enhanced prostaglandin (PG) or leukotriene (LT) synthesis. While Asc was found to increase both lipid peroxidation and PG synthesis in the cells, these mechanisms and enhanced LT synthesis did not appear to have played a role in the inhibition of cell growth by Asc or in the growth inhibitory interaction between Asc and the EF As. In vivo studies revealed that diets containing essential or polyunsaturated fatty acids (EFAs/PUFAs) in the form of vegetable oils, and in particular GLA in the form of evening primrose oil, significantly promoted melanoma growth in mice when compared with an EFA/PUFA free diet containing predominantly saturated fats (SF). Supplementary dietary Asc in contrast was found to significantly inhibit melanoma growth in mice fed EFA/PUFA, and in particular GLA, containing diets but not in mice fed SF cont~g diets. This result appears to indicate the occurrence of an interaction between the two nutrients. Ul The mechanism of tumour promotion by the EP As/PUP As did not appear to have involved enhanced PG or LT synthesis or lipid peroxidation. Since dietary EPA/PUPA manipulation was found to significantly alter the EPA content of tissues, including the melanomas, the mechanism of tumour promotion may have involved changes in the EPA composition of the tumour cells. While supplementary Asc was found to significantly increase the Asc content of certain tissues, including the melanomas, which may have played a role in tumour growth inhibition by Asc, it was found not to affect the EPA content of tissues. Enhanced PG or LT synthesis and lipid perox:idation did not appear to have been involved in the tumour growth inhibitory interaction between Asc and the EP As/PUP As. THe activity of the enzyme delta-6-desaturase, a key enzyme in EF A metabolism which catalyses the desaturation of LA to GLA, and the influence of Asc on activity of the enzyme were also examined. The cultured cells, and BL6 cells in particular, were found to contain significant activity of the enzyme. Whereas murine liver microsomal fractions were found to contain delta-6-desaturase activity, microsomes from melanomas grown in mice were found to lack activity of the enzyme. The significant tumour promoting effects of the GLA containing EPO diet may have been the result of the lack of delta-6-desaturase activity in tumour cells grown in mice. Asc was found to stimulate activity of the enzyme in cultured BL6 cells but not in LLCM.K cells, while dietary Asc and EF A/PUP A manipulation did not influence activity of the enzyme in microsomal fractions. This study has confirmed previous reports of the in vivo tumour promoting effects of dietary EP As/PUP As and the tumour growth inhibitory effects of Asc. The in vitro cell growth inhibitory effects of Asc and the EP As also confirm the results of previous reports. Previous studies investigating possible interactions between Asc and EP As/PUP As in influencing tumour cell growth could not be located in the relevant literature. This study may therefore be one of the first investigations of any such interaction between these nutrients in tumour cells. While this study was not able to identify the mechanisms involved in the different tumour promoting or tumour growth inhibitory effects of the two nutrients in the two systems, it did eliminate a number of potential mechanisms. The results of this study also emphasise the difficulty of attempting to compare the results of in vitro and in vivo studies.
- Full Text:
- Date Issued: 1990
Isolation of and interaction of nutrients with the linoleoyl-coa desaturase complex
- Authors: Perkins, Denise Mary
- Date: 1990
- Subjects: Cell proliferation , Cancer cells -- Growth -- Regulation , Enzymes -- Purification
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4558 , http://hdl.handle.net/10962/d1018264
- Description: The termina1 enzyme in the linoleoyl-CoA desaturase enzyme complex, delta-6-desaturase was implied in the control of cell proliferation in cancer cells. One of the aims of this study was to isolate the terminal enzyme. It was decided that in order to isolate this enzyme it was first necessary to isolate the entire complex and then to enzymatically solubilise the first two components of the complex i e cytochrome b5 reductase and cytochrome b5 from the complex resulting in a pure delta-6-desaturase . The first two components were isolated and purified using simplified and easily reproducible methodologies which could be utilised in the final purification of delta-6- desaturase. The entire enzyme complex, linoleoyl-CoA desaturase was also isolated in a pure form and this pure complex was used to attempt to isolate delta-6-desaturase. The terminal enzyme was isolated with some cytochrome b5 still bound to it. The methods used had proven to be successful and with some modifications should yield a pure enzyme. Zinc and GLA were known to play a role in the inhibition of cancer cell proliferation and zinc was hypothesised to inhibit cell growth by stimulating the activity of the linoleoyl-CoA desaturase enzyme complex which is involved in the regulation of cell proliferation. GLA is the product of the reaction that this enzyme complex catalyses and GLA has been shown to inhibit cancer ce ll growth. The effect of GLA on cell growth and linoleoyl-CoA desaturase activity was thus investigated. Results showed that both zinc and GLA inhibited cell growth and that the combined addition of zinc and GLA generally resulted in the inhibition of cell growth and the activation of linoleoyl-CoA desaturase activity in the BL-6 cells while having a less pronounced effect on the LLCMK cells. The results of this study support the hypothesis that zinc may be a cofactor of linoleoyl-CoA desaturase.
- Full Text:
- Date Issued: 1990
- Authors: Perkins, Denise Mary
- Date: 1990
- Subjects: Cell proliferation , Cancer cells -- Growth -- Regulation , Enzymes -- Purification
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4558 , http://hdl.handle.net/10962/d1018264
- Description: The termina1 enzyme in the linoleoyl-CoA desaturase enzyme complex, delta-6-desaturase was implied in the control of cell proliferation in cancer cells. One of the aims of this study was to isolate the terminal enzyme. It was decided that in order to isolate this enzyme it was first necessary to isolate the entire complex and then to enzymatically solubilise the first two components of the complex i e cytochrome b5 reductase and cytochrome b5 from the complex resulting in a pure delta-6-desaturase . The first two components were isolated and purified using simplified and easily reproducible methodologies which could be utilised in the final purification of delta-6- desaturase. The entire enzyme complex, linoleoyl-CoA desaturase was also isolated in a pure form and this pure complex was used to attempt to isolate delta-6-desaturase. The terminal enzyme was isolated with some cytochrome b5 still bound to it. The methods used had proven to be successful and with some modifications should yield a pure enzyme. Zinc and GLA were known to play a role in the inhibition of cancer cell proliferation and zinc was hypothesised to inhibit cell growth by stimulating the activity of the linoleoyl-CoA desaturase enzyme complex which is involved in the regulation of cell proliferation. GLA is the product of the reaction that this enzyme complex catalyses and GLA has been shown to inhibit cancer ce ll growth. The effect of GLA on cell growth and linoleoyl-CoA desaturase activity was thus investigated. Results showed that both zinc and GLA inhibited cell growth and that the combined addition of zinc and GLA generally resulted in the inhibition of cell growth and the activation of linoleoyl-CoA desaturase activity in the BL-6 cells while having a less pronounced effect on the LLCMK cells. The results of this study support the hypothesis that zinc may be a cofactor of linoleoyl-CoA desaturase.
- Full Text:
- Date Issued: 1990
Synthetic studies of swazinecic acid dilactone
- Authors: Liddell, James Richard
- Date: 1989
- Subjects: Phrrolizidines Alkaloids -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4298 , http://hdl.handle.net/10962/d1004668
- Description: The occurrence and syntheses of the pyrrolizidine alkaloids from 1976 to March 1988 is reviewed, and a stereoselective total synthesis of swazinecic acid dilactone was attempted. One approach involved an asymmetric synthesis of the allylic α-hydroxy acid 2-hydroxy-2,3-dimethyl-3-butenoic acid employing oxazolines as chiral auxilaries. The oxazoline, (4S,5S)-2-(1-bromoethyl)-4-methoxymethyl-5-phenyl-2-oxazoline, was obtained by direct halogenation of the 2-ethyl oxazoline analogue. This was condensed with acetone in a Darzens type reaction and the resultant epoxy oxazoline rearranged to an allylic α-hydroxy oxazoline which was then hydrolysed to the chiral hydroxy acid in low enantiomeric excess. The hydroxy acid, as the O-silylated ethyl ester, was elaborated by allylic diethyl malonate to bromination and condensation with diethyl 5-carboethoxy-2-methyl-3- methylene-2-0-tert-butyldimethylsilylhexanedioate. Removal of the silyl protecting group and epoxidation provided an epoxy triester, which on hydrolysis provided a mixture of acids of uncertain structures.
- Full Text:
- Date Issued: 1989
- Authors: Liddell, James Richard
- Date: 1989
- Subjects: Phrrolizidines Alkaloids -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4298 , http://hdl.handle.net/10962/d1004668
- Description: The occurrence and syntheses of the pyrrolizidine alkaloids from 1976 to March 1988 is reviewed, and a stereoselective total synthesis of swazinecic acid dilactone was attempted. One approach involved an asymmetric synthesis of the allylic α-hydroxy acid 2-hydroxy-2,3-dimethyl-3-butenoic acid employing oxazolines as chiral auxilaries. The oxazoline, (4S,5S)-2-(1-bromoethyl)-4-methoxymethyl-5-phenyl-2-oxazoline, was obtained by direct halogenation of the 2-ethyl oxazoline analogue. This was condensed with acetone in a Darzens type reaction and the resultant epoxy oxazoline rearranged to an allylic α-hydroxy oxazoline which was then hydrolysed to the chiral hydroxy acid in low enantiomeric excess. The hydroxy acid, as the O-silylated ethyl ester, was elaborated by allylic diethyl malonate to bromination and condensation with diethyl 5-carboethoxy-2-methyl-3- methylene-2-0-tert-butyldimethylsilylhexanedioate. Removal of the silyl protecting group and epoxidation provided an epoxy triester, which on hydrolysis provided a mixture of acids of uncertain structures.
- Full Text:
- Date Issued: 1989
The thermodynamics of binary liquid mixtures of compounds containing multiple bonds.
- Authors: Baxter, Rodney Charles
- Date: 1989
- Subjects: Solution (Chemistry)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4531 , http://hdl.handle.net/10962/d1016079
- Description: Excess thermodynamic properties have been determined for several binary liquid mixtures with the aim of testing various thermodynamic theories and postulates. Excess molar enthalpies, HEm, have been determined using an LKB flow microcalorimeter and excess molar volumes, VEm, have been determined using an Anton Paar vibrating tube densitometer. The activity coefficients at infinite dilution ƴ∞₁₃, have been determined using an atmospheric pressure gas-liquid chromatograph. The excess molar enthalpies and the excess molar volumes have been measured at 298.15 K for systems involving the bicyclic compounds decahydronaphthalene (decalin), 1,2,3,4-tetrahydronaphthalene (tetralin), bicyclohexyl, or cyclohexylbenzene mixed with 1- hexene, 1-hexyne, 1-heptene, 1-heptyne, cyclohexene, 1,3-cyclohexadiene, 1,4- cyclohexadiene, or benzene. These excess properties have also been measured for systems where the bicyclic compound has been replaced with benzene, cyclohexane or n-hexane. The results show defmite trends related to the size, shape, and the degree of unsaturation of the component molecules. The Flory theory has been used to predict excess molar enthalpies and excess molar volumes for {(a bicyclic compound or benzene or cyclohexane or n-hexane) +(an n-alkane or a 1-alkene or a 1-alkyne or a cycloalkane or cyclohexene or a cycloalkadiene or benzene)}. The one parameter equations offer reasonably good correlations between the predicted and the experimental results. More insight into the origins of the contnbutions to the excess thermodynamic properties for these systems has been gained by considering the approximate equations of Patterson and co-workers, which separate the interactional and the free volume contributions to the excess molar enthalpy and the excess molar volume. The one parameter equations have adequately rationalized a good deal of the observed behaviour for HEm and VEm. The theory of Liebermann and co-workers, which does not employ any adjustable parameters, has not been as successful at predicting the excess thermodynamic properties for the above systems. The activity coefficients at infinite dilution have been measured at 278.15 K, 288.15 K and 298.15 K for n-bexane, 1-bexene, 1-hexyne, n-heptane, 1-heptene, 1-heptyne, cyclohexane, cyclohexene, 1,3-cyclohexadiene, 1,4-cyclohexadiene, and benzene, in decalin, tetralin, bicyclohexyl, and cyclohexylbenzene. Solvent losses from the column have been accounted for by an extrapolation procedure. The activity coefficient results together with the HEm and VEm values have been used to calculate the partial molar excess thermodynamic properties of mixing at infinite dilution. The partial molar excess properties at infinite dilution for decalin mixtures are similar to those for bicyclohexyl mixtures. There is also a similarity between the properties of the tetralin mixtures and the cyclohexylbenzene mixtures. The cycloalkadienes, benzene and the 1-alkynes exhibit a strong dissociation effect on being mixed with the saturated solvents, decalin and bicyclohexyl, but associate strongly with tetralin and with cyclohexylbenzene. The Flory theory bas been used to predict activity coefficients at infinite dilution from the experimentally determined HEm results for { (n-bexane or 1-hexene or 1-hexyne or naheptane or 1-heptene or 1-beptyne) + (a bicyclic compound)}. The theory is much better at predicting values for mixtures where both components are either saturated molecules or are unsaturated molecules than for {saturated + unsaturated} mixtures.
- Full Text:
- Date Issued: 1989
- Authors: Baxter, Rodney Charles
- Date: 1989
- Subjects: Solution (Chemistry)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4531 , http://hdl.handle.net/10962/d1016079
- Description: Excess thermodynamic properties have been determined for several binary liquid mixtures with the aim of testing various thermodynamic theories and postulates. Excess molar enthalpies, HEm, have been determined using an LKB flow microcalorimeter and excess molar volumes, VEm, have been determined using an Anton Paar vibrating tube densitometer. The activity coefficients at infinite dilution ƴ∞₁₃, have been determined using an atmospheric pressure gas-liquid chromatograph. The excess molar enthalpies and the excess molar volumes have been measured at 298.15 K for systems involving the bicyclic compounds decahydronaphthalene (decalin), 1,2,3,4-tetrahydronaphthalene (tetralin), bicyclohexyl, or cyclohexylbenzene mixed with 1- hexene, 1-hexyne, 1-heptene, 1-heptyne, cyclohexene, 1,3-cyclohexadiene, 1,4- cyclohexadiene, or benzene. These excess properties have also been measured for systems where the bicyclic compound has been replaced with benzene, cyclohexane or n-hexane. The results show defmite trends related to the size, shape, and the degree of unsaturation of the component molecules. The Flory theory has been used to predict excess molar enthalpies and excess molar volumes for {(a bicyclic compound or benzene or cyclohexane or n-hexane) +(an n-alkane or a 1-alkene or a 1-alkyne or a cycloalkane or cyclohexene or a cycloalkadiene or benzene)}. The one parameter equations offer reasonably good correlations between the predicted and the experimental results. More insight into the origins of the contnbutions to the excess thermodynamic properties for these systems has been gained by considering the approximate equations of Patterson and co-workers, which separate the interactional and the free volume contributions to the excess molar enthalpy and the excess molar volume. The one parameter equations have adequately rationalized a good deal of the observed behaviour for HEm and VEm. The theory of Liebermann and co-workers, which does not employ any adjustable parameters, has not been as successful at predicting the excess thermodynamic properties for the above systems. The activity coefficients at infinite dilution have been measured at 278.15 K, 288.15 K and 298.15 K for n-bexane, 1-bexene, 1-hexyne, n-heptane, 1-heptene, 1-heptyne, cyclohexane, cyclohexene, 1,3-cyclohexadiene, 1,4-cyclohexadiene, and benzene, in decalin, tetralin, bicyclohexyl, and cyclohexylbenzene. Solvent losses from the column have been accounted for by an extrapolation procedure. The activity coefficient results together with the HEm and VEm values have been used to calculate the partial molar excess thermodynamic properties of mixing at infinite dilution. The partial molar excess properties at infinite dilution for decalin mixtures are similar to those for bicyclohexyl mixtures. There is also a similarity between the properties of the tetralin mixtures and the cyclohexylbenzene mixtures. The cycloalkadienes, benzene and the 1-alkynes exhibit a strong dissociation effect on being mixed with the saturated solvents, decalin and bicyclohexyl, but associate strongly with tetralin and with cyclohexylbenzene. The Flory theory bas been used to predict activity coefficients at infinite dilution from the experimentally determined HEm results for { (n-bexane or 1-hexene or 1-hexyne or naheptane or 1-heptene or 1-beptyne) + (a bicyclic compound)}. The theory is much better at predicting values for mixtures where both components are either saturated molecules or are unsaturated molecules than for {saturated + unsaturated} mixtures.
- Full Text:
- Date Issued: 1989
Extractives from six species of Lamiaceae
- Davies-Coleman, Michael Trevor
- Authors: Davies-Coleman, Michael Trevor
- Date: 1988
- Subjects: Lamiaceae
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4532 , http://hdl.handle.net/10962/d1016235
- Description: In continuation of the phytochemical studies of plants belonging to the Lamiaceae (formerly Labiatae) the acetone extractives of six Southern African species from this family have been examined. The genus Syncolostemon has not been investigated before and a new 6- substituted-5 ,6-dihydro-a-pyrone , synrotolide was isolated from S. rotundifolius. The structure of synrotolide was fully elucidated as 6fixii [3'R, 61S-(diacetyloxy)-4 1R, 5 1 8-(dihydroxy)-1~-hepteny~ -5,6-dihydro-2H-pyran- 2-one. Oleanolic acid is the major component of both~ rotundifolius and S. densifloris. The flavonol quercetin was isolated from S. densifloris as its 3, 3', 4' , 7 tetramethyl ether. A further 6-substituted-5,6-dihydro-a-pyrone, boronolide, was obtained from Tetradenia barberae. The structure of boronolide was known but the absolute stereochemistry was unassigned. Chemical degradation established the total structure of this compound as 6R- [1 'R, 2'R, 3's -(trisacetyloxy)heptyl] -5,6-dihydro-2H-pyran-2-one. The chemistry of naturally occuring 6-substituted-5,6-dihydro-apyrones has not as such been previously reviewed and a comprehensive review covering the literature up to June 1987 is presented here. Three known labdane diterpenoids nepetaefuran, hispanalone and dubiin were iso lated from Leonotis nepetaefolia, Ballota africana and L. ocymifolia var. ocymifolia (formerly~ dubia). Both~ nepetaefolia and L. dubia have been examined before. An X-ray analysis of saponified dubiin and a circular dichroism study of 6-deacetyldehydrodubiin and related compounds corroborated the structure of dubiin as 48, 5R, 6R, 8R, 9R, 10R-[6-acetoxy-15,16-epoxy-9-hydroxylabda-13 (16), 14-dien-19, 20- olactoneJ. The chemotaxonomic relationships of the genera Ballota and Leonotis are discussed.
- Full Text:
- Date Issued: 1988
- Authors: Davies-Coleman, Michael Trevor
- Date: 1988
- Subjects: Lamiaceae
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4532 , http://hdl.handle.net/10962/d1016235
- Description: In continuation of the phytochemical studies of plants belonging to the Lamiaceae (formerly Labiatae) the acetone extractives of six Southern African species from this family have been examined. The genus Syncolostemon has not been investigated before and a new 6- substituted-5 ,6-dihydro-a-pyrone , synrotolide was isolated from S. rotundifolius. The structure of synrotolide was fully elucidated as 6fixii [3'R, 61S-(diacetyloxy)-4 1R, 5 1 8-(dihydroxy)-1~-hepteny~ -5,6-dihydro-2H-pyran- 2-one. Oleanolic acid is the major component of both~ rotundifolius and S. densifloris. The flavonol quercetin was isolated from S. densifloris as its 3, 3', 4' , 7 tetramethyl ether. A further 6-substituted-5,6-dihydro-a-pyrone, boronolide, was obtained from Tetradenia barberae. The structure of boronolide was known but the absolute stereochemistry was unassigned. Chemical degradation established the total structure of this compound as 6R- [1 'R, 2'R, 3's -(trisacetyloxy)heptyl] -5,6-dihydro-2H-pyran-2-one. The chemistry of naturally occuring 6-substituted-5,6-dihydro-apyrones has not as such been previously reviewed and a comprehensive review covering the literature up to June 1987 is presented here. Three known labdane diterpenoids nepetaefuran, hispanalone and dubiin were iso lated from Leonotis nepetaefolia, Ballota africana and L. ocymifolia var. ocymifolia (formerly~ dubia). Both~ nepetaefolia and L. dubia have been examined before. An X-ray analysis of saponified dubiin and a circular dichroism study of 6-deacetyldehydrodubiin and related compounds corroborated the structure of dubiin as 48, 5R, 6R, 8R, 9R, 10R-[6-acetoxy-15,16-epoxy-9-hydroxylabda-13 (16), 14-dien-19, 20- olactoneJ. The chemotaxonomic relationships of the genera Ballota and Leonotis are discussed.
- Full Text:
- Date Issued: 1988