Applications of Baylis-Idllman methodology in the synthesis of chromene derivatives
- Authors: Nocanda, Xolani Wittleton
- Date: 2001
- Subjects: Heterocyclic chemistry , Heterocyclic compounds -- Derivatives
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4556 , http://hdl.handle.net/10962/d1018257
- Description: The reaction of salicylaldehyde with various activated alkenes, viz., methyl vinyl ketone, ethyl vinyl ketone, phenyl vinyl sulfone, phenyl vinylsulfonate, acrolein and acrylonitrile, under Baylis-Hillman conditions, has been found to proceed with the chemoselective formation of chromene derivatives. The reaction conditions have been optimised and chromene derivatives have been obtained in isolated yields up to 87 %. The generality of the reaction, using 1,4-diazabicyclo[2.2.2]octane (DABCO), as the catalyst, and a heterogeneous (chloroform-water) solvent system, has been established using a range of salicylaldehyde derivatives,. including 2-hydroxynaphthaldehyde. The formation of chromene derivatives, under these conditions, has been assumed to proceed via an initial, Baylis-Hillman reaction, followed by cyclisation involving intramolecular conjugate addition, and subsequent dehydration. Evidence supporting this sequence has been obtained from the isolation ofBaylis-Hillman products from reactions involving the use of tertbutylclimethylsilyl-protected salicylaldehyde, 4-hydroxybenzaldehyde and tert-butyl acrylate as substrates. The potential of the ''Baylis-Hillman zwitterion" to participate as a donor species in Michael-type addition reactions has been explored and a series of climeric products has been isolated. The Baylis-Hillman methodology has also been successfully extended to the synthesis of sulfurcontaining heterocyclic systems, and a range of 3-substituted thiochromenes has been obtained in moderate yields, using 2,2'-dithiobenzaldehyde and various activated alkenes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst. The electron-impact mass spectra of selected chromene and thiocbromene derivatives have been investigated permitting comparison of the fragmentation of the oxygen- and sulfur-containing analogues. In a study directed at the synthesis of potential HIV -1 protease inhibitors, chromene- and thiocbromene-containing analogues of the clinically useful drug, ritonavir, have been prepared. Thiochromene and chromene derivatives were converted to the corresponding 3 -carboxylic acids and coupled with a specially prepared, hydroxyethylene dipeptide isostere to afford ritonavir analogues containing cbromene and thiochromene termini in ca. 60% yield.
- Full Text:
- Date Issued: 2001
- Authors: Nocanda, Xolani Wittleton
- Date: 2001
- Subjects: Heterocyclic chemistry , Heterocyclic compounds -- Derivatives
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4556 , http://hdl.handle.net/10962/d1018257
- Description: The reaction of salicylaldehyde with various activated alkenes, viz., methyl vinyl ketone, ethyl vinyl ketone, phenyl vinyl sulfone, phenyl vinylsulfonate, acrolein and acrylonitrile, under Baylis-Hillman conditions, has been found to proceed with the chemoselective formation of chromene derivatives. The reaction conditions have been optimised and chromene derivatives have been obtained in isolated yields up to 87 %. The generality of the reaction, using 1,4-diazabicyclo[2.2.2]octane (DABCO), as the catalyst, and a heterogeneous (chloroform-water) solvent system, has been established using a range of salicylaldehyde derivatives,. including 2-hydroxynaphthaldehyde. The formation of chromene derivatives, under these conditions, has been assumed to proceed via an initial, Baylis-Hillman reaction, followed by cyclisation involving intramolecular conjugate addition, and subsequent dehydration. Evidence supporting this sequence has been obtained from the isolation ofBaylis-Hillman products from reactions involving the use of tertbutylclimethylsilyl-protected salicylaldehyde, 4-hydroxybenzaldehyde and tert-butyl acrylate as substrates. The potential of the ''Baylis-Hillman zwitterion" to participate as a donor species in Michael-type addition reactions has been explored and a series of climeric products has been isolated. The Baylis-Hillman methodology has also been successfully extended to the synthesis of sulfurcontaining heterocyclic systems, and a range of 3-substituted thiochromenes has been obtained in moderate yields, using 2,2'-dithiobenzaldehyde and various activated alkenes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst. The electron-impact mass spectra of selected chromene and thiocbromene derivatives have been investigated permitting comparison of the fragmentation of the oxygen- and sulfur-containing analogues. In a study directed at the synthesis of potential HIV -1 protease inhibitors, chromene- and thiocbromene-containing analogues of the clinically useful drug, ritonavir, have been prepared. Thiochromene and chromene derivatives were converted to the corresponding 3 -carboxylic acids and coupled with a specially prepared, hydroxyethylene dipeptide isostere to afford ritonavir analogues containing cbromene and thiochromene termini in ca. 60% yield.
- Full Text:
- Date Issued: 2001
A synthetic and spectrometric study of the initial phases in urea-formaldehyde resin formation
- Authors: Nocanda, Xolani Wittleton
- Date: 1998
- Subjects: Phenolic resins , Gums and resins, Synthetic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4383 , http://hdl.handle.net/10962/d1005048 , Phenolic resins , Gums and resins, Synthetic
- Description: In a series ofpreIiminary studies of urea-formaldehyde reactions, the influence of the U:F molar ratio, the temperature and the catalyst were investigated. Subsequently, in a more rigorous evaluation of the influence of four variables on urea-formaldehyde resin formation, viz., U:F molar ratio, pH, temperature and reaction time, a set of twenty reactions were performed using a statistical approach. The results indicate that high resin viscosity is best achieved by using a high U:F molar ratio (1:2) and conducting the reaction at 90°C. Several basic components produced in urea-formaldehyde reactions have been synthesised, characterised by NMR spectroscopy, silylated using bis(trimethylsilyl)trifluoroacetamide and analysed by low resolution mass spectrometry. The use oftriazones as cross-linking agents has been investigated, and a series of 5-substituted triazones have been prepared and their mass fragmentation patterns explored using a combination of low and high resolution mass spectrometry. In order to facilitate interpretation of ¹³C NMR data obtained for U-F resins, internal rotation in various urea derivatives was investigated using variable temperature ¹H and ¹³C NMR spectroscopic study. Signal splittings observed below 247 K have been rationalised in terms of various rotameric structures.
- Full Text:
- Date Issued: 1998
- Authors: Nocanda, Xolani Wittleton
- Date: 1998
- Subjects: Phenolic resins , Gums and resins, Synthetic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4383 , http://hdl.handle.net/10962/d1005048 , Phenolic resins , Gums and resins, Synthetic
- Description: In a series ofpreIiminary studies of urea-formaldehyde reactions, the influence of the U:F molar ratio, the temperature and the catalyst were investigated. Subsequently, in a more rigorous evaluation of the influence of four variables on urea-formaldehyde resin formation, viz., U:F molar ratio, pH, temperature and reaction time, a set of twenty reactions were performed using a statistical approach. The results indicate that high resin viscosity is best achieved by using a high U:F molar ratio (1:2) and conducting the reaction at 90°C. Several basic components produced in urea-formaldehyde reactions have been synthesised, characterised by NMR spectroscopy, silylated using bis(trimethylsilyl)trifluoroacetamide and analysed by low resolution mass spectrometry. The use oftriazones as cross-linking agents has been investigated, and a series of 5-substituted triazones have been prepared and their mass fragmentation patterns explored using a combination of low and high resolution mass spectrometry. In order to facilitate interpretation of ¹³C NMR data obtained for U-F resins, internal rotation in various urea derivatives was investigated using variable temperature ¹H and ¹³C NMR spectroscopic study. Signal splittings observed below 247 K have been rationalised in terms of various rotameric structures.
- Full Text:
- Date Issued: 1998
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