Chemical studies of necic acid analogues
- Guthrie-Strachan, Jeffry James
- Authors: Guthrie-Strachan, Jeffry James
- Date: 1997
- Subjects: Organic acids , Chemistry, Organic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4425 , http://hdl.handle.net/10962/d1006909 , Organic acids , Chemistry, Organic
- Description: Various aldehydes have been reacted with methyl acrylate under Baylis-Hillman conditions, using DABCO as a catalyst, to afford a range of α-substituted acrylic esters containing an allylic hydroxy group. Selected Baylis-Hillman products have been brominated, hydrolysed and acetylated to afford substrates for the synthesis of necic acid analogues. The diastereo- and regioselectivity of nucleophilic attack, using sodium methylmercaptan, on the Baylis-Hillman products and selected brominated derivatives was investigated. The allylic hydroxy compounds favour conjugate addition with the generation of a new chiral centre, while the allylic bromo derivatives favour substitution (SN and SN') (S[subscript N] and S[subscript N]') with consequent loss of chirality. (E)-2-Isopropylcrotonic acid, a vital precursor in the synthesis of all stereoisomers of trachelanthic and viridifloric acid, was synthesised in an attempt to obtain the necic acid components required for total alkaloid synthesis of lycopsamine and its derivatives. This precursor and salicylic acid were then used to prepare esters of retronecine, a dihydroxy necine base obtained via extraction and consequent hydrolysis of retrorsine.
- Full Text:
- Date Issued: 1997
- Authors: Guthrie-Strachan, Jeffry James
- Date: 1997
- Subjects: Organic acids , Chemistry, Organic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4425 , http://hdl.handle.net/10962/d1006909 , Organic acids , Chemistry, Organic
- Description: Various aldehydes have been reacted with methyl acrylate under Baylis-Hillman conditions, using DABCO as a catalyst, to afford a range of α-substituted acrylic esters containing an allylic hydroxy group. Selected Baylis-Hillman products have been brominated, hydrolysed and acetylated to afford substrates for the synthesis of necic acid analogues. The diastereo- and regioselectivity of nucleophilic attack, using sodium methylmercaptan, on the Baylis-Hillman products and selected brominated derivatives was investigated. The allylic hydroxy compounds favour conjugate addition with the generation of a new chiral centre, while the allylic bromo derivatives favour substitution (SN and SN') (S[subscript N] and S[subscript N]') with consequent loss of chirality. (E)-2-Isopropylcrotonic acid, a vital precursor in the synthesis of all stereoisomers of trachelanthic and viridifloric acid, was synthesised in an attempt to obtain the necic acid components required for total alkaloid synthesis of lycopsamine and its derivatives. This precursor and salicylic acid were then used to prepare esters of retronecine, a dihydroxy necine base obtained via extraction and consequent hydrolysis of retrorsine.
- Full Text:
- Date Issued: 1997
Design, synthesis and evaluation of novel, metal complexing agents
- Authors: Hagemann, Justin Philip
- Date: 1997
- Subjects: Ligands Metal complexes
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4307 , http://hdl.handle.net/10962/d1004965
- Description: Various chelating ligands have been designed and synthesised; these include amino-amide ligands, tetraacetic acid systems and sulfur-containing amide ligands. Difficulties in the synthesis and purification of the amino-amide ligands were largely overcome, permitting the mono acylation of ethylenediamine and the synthesis of bis(2-aminoethyl)-2-benzylpropanediamide. Novel tetraacetic acid ligands, based on the propanediamide backbone and targeted as EDTA analogues, were obtained from their methyl and benzyl esters; but the instability of the tetraacids prevented their full characterisation. Bidentate, tridentate and tetradentate sulfur-containing monoamide ligands, based on the ortho-thio acetanilide moiety, were designed to specifically chelate platinum and palladium in the presence of base metals. In their synthesis, thiocyanation was used to introduce the orth-thio group on para-substituted anilines, and further functionalisation was achieved via appropriate protection of nucleophilic sulfur moieties. A range of tetradentate, sulfur-containing diamide ligands was also synthesised by reacting substituted 2-mercaptoacetanilides with 1,2- dibromoethane. Novel ligands were characterised by spectroscopic (¹H and ¹³C NMR; IR and M S) techniques and elemental (combustion and high resolution MS) analysis. Computer modelling and ¹H NMR chemical shift data have been used to explore the conformational preferences of the sulfur-containing acetanilide ligands. The macrocyclic ligands and systems with ortho-methylthio substituents appear to exhibit the greatest degree of coplanarity of the aromatic and amide functions. Solvent extraction studies revealed that the sulfur-containing amide ligands selectively extracted palladium(II) from platinum(II), copper(II}, nickel(II} and cobalt(II}. Even though the palladium(II} was extracted from an acidic medium, certain monoamide ligands were able to complex palladium(II) through their sulfur and deprotonated amide nitrogen donors, a trithia monoamide ligand being observed to displace all the chloride ligands on palladium to form a monomeric tetracoordinate complex. The diamide ligands, however, appeared to favour extraction of palladium(II) by coordination through their sulfur donors, forming 5-membered sulfur-sulfur chelates. In basic media (pH 8-9), selected sulfur-containing monoamide and diamide ligands have been shown to complex platinum(II) and palladium(II) through their sulfur and deprotonated amide nitrogen donors. At neutral pH, a dimercapto monoamide ligand has been shown to complex platinum from cisplatin with partial expulsion of the ammine ligands, while a macrocyclic trithia monoamide ligand has been observed to complex platinum from tetrachloroplatinate with concomitant deprotonation of the amide nitrogen. Where possible, the complexes were characterised by infrared and ¹H NMR spectroscopy and have also been studied using the computer modelling soft-ware programmes, Momec® and Hyperchem®.
- Full Text:
- Date Issued: 1997
- Authors: Hagemann, Justin Philip
- Date: 1997
- Subjects: Ligands Metal complexes
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4307 , http://hdl.handle.net/10962/d1004965
- Description: Various chelating ligands have been designed and synthesised; these include amino-amide ligands, tetraacetic acid systems and sulfur-containing amide ligands. Difficulties in the synthesis and purification of the amino-amide ligands were largely overcome, permitting the mono acylation of ethylenediamine and the synthesis of bis(2-aminoethyl)-2-benzylpropanediamide. Novel tetraacetic acid ligands, based on the propanediamide backbone and targeted as EDTA analogues, were obtained from their methyl and benzyl esters; but the instability of the tetraacids prevented their full characterisation. Bidentate, tridentate and tetradentate sulfur-containing monoamide ligands, based on the ortho-thio acetanilide moiety, were designed to specifically chelate platinum and palladium in the presence of base metals. In their synthesis, thiocyanation was used to introduce the orth-thio group on para-substituted anilines, and further functionalisation was achieved via appropriate protection of nucleophilic sulfur moieties. A range of tetradentate, sulfur-containing diamide ligands was also synthesised by reacting substituted 2-mercaptoacetanilides with 1,2- dibromoethane. Novel ligands were characterised by spectroscopic (¹H and ¹³C NMR; IR and M S) techniques and elemental (combustion and high resolution MS) analysis. Computer modelling and ¹H NMR chemical shift data have been used to explore the conformational preferences of the sulfur-containing acetanilide ligands. The macrocyclic ligands and systems with ortho-methylthio substituents appear to exhibit the greatest degree of coplanarity of the aromatic and amide functions. Solvent extraction studies revealed that the sulfur-containing amide ligands selectively extracted palladium(II) from platinum(II), copper(II}, nickel(II} and cobalt(II}. Even though the palladium(II} was extracted from an acidic medium, certain monoamide ligands were able to complex palladium(II) through their sulfur and deprotonated amide nitrogen donors, a trithia monoamide ligand being observed to displace all the chloride ligands on palladium to form a monomeric tetracoordinate complex. The diamide ligands, however, appeared to favour extraction of palladium(II) by coordination through their sulfur donors, forming 5-membered sulfur-sulfur chelates. In basic media (pH 8-9), selected sulfur-containing monoamide and diamide ligands have been shown to complex platinum(II) and palladium(II) through their sulfur and deprotonated amide nitrogen donors. At neutral pH, a dimercapto monoamide ligand has been shown to complex platinum from cisplatin with partial expulsion of the ammine ligands, while a macrocyclic trithia monoamide ligand has been observed to complex platinum from tetrachloroplatinate with concomitant deprotonation of the amide nitrogen. Where possible, the complexes were characterised by infrared and ¹H NMR spectroscopy and have also been studied using the computer modelling soft-ware programmes, Momec® and Hyperchem®.
- 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
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