Tetrol and derivatives: synthesis, host-guest properties and racemate resolutions
- Authors: Pohl, Pieter Lourens
- Date: 2015
- Subjects: Chemistry, Organic , Chirality , Asymmetric synthesis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/2879 , vital:20359
- Description: In this study, we investigated the potential of a novel chiral host compound (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and its derivatives for use in racemate resolution using host-guest chemistry. The parent TETROL molecule is composed of a butane chain bearing a hydroxy functionality on each carbon, and two phenyl rings on each of the terminal carbons. The two internal carbon atoms are chiral. The syntheses of TETROL and derivatives were carried out by modifying the diester of naturally-occurring optically active tartaric acid using a variety of aromatic Grignard reagents. These included phenyl, anisyl, tolyl and naphthyl groups, as well as aromatic rings bearing fluoro and trifluoromethyl substitutents. The substituents on the aromatic rings were located in the ortho, meta or para positions. The so-obtained potential host compounds were investigated for their inclusion abilities by recrystallizing them from a number of potential chiral guest compounds such as 2- and 3-methylcyclohexanone, camphor, i-propanol and 2-butanol, as well as various achiral organic compounds. Host:guest ratios were determined by means of 1H-NMR spectroscopy. Of the hosts investigated, TETROL appeared to favour a host:guest ratio of 1:1 for all included compounds. It complexed with cyclic ketones such as cyclohexanone and derivatives, and also cyclic alcohols and amines like cyclohexanol and morpholine. TETROL, however, was not able to include short chain or branched chain alcohols such as i-propanol and 2-butanol. p-AnisylTETROL showed similar inclusion abilities to TETROL but, in addition, enclathrated i-propanol and 2-butanol. p-TolylTETROL showed a preference for the inclusion of alcohols over ketones. In general, the ortho-substituted aromatic derivatives of TETROL faired relatively poorly as hosts, with some exceptions. Of the hosts investigated, TETROL appeared to favour a host:guest ratio of 1:1 for all included compounds. It complexed with cyclic ketones such as cyclohexanone and derivatives, and also cyclic alcohols and amines like cyclohexanol and morpholine. TETROL, however, was not able to include short chain or branched chain alcohols such as i-propanol and 2-butanol. p-AnisylTETROL showed similar inclusion abilities to TETROL but, in addition, enclathrated i-propanol and 2-butanol. p-TolylTETROL showed a preference for the inclusion of alcohols over ketones. In general, the ortho-substituted aromatic derivatives of TETROL faired relatively poorly as hosts, with some exceptions. X-Ray data of the inclusion complexes indicated that a pair of 1,3-intramolecular hydrogen bonds was a significant stabilizing factor of the geometries of all the hosts. The guest was always held in the host crystal by means of a hydrogen bond with the host, where the host functioned as the hydrogen bond donor and the guest as the acceptor. There were a number of other inter- and intra-molecular contacts that further stabilized the inclusion complexes. A surprising feature of the inclusion of 3-methylcyclohexanone, as elucidated by X-ray analysis, was that its methyl group adopted the axial orientation, the higher energy conformation for these kinds of molecules, and a 3-alkylketone effect was proposed to be one of the reasons for this observation. Thermal data was used to assess the relative thermal stabilities of the complexes, and the results compared with features of the X-ray structures, in order to determine whether thermal stability is related in some way to the nature of the guest packing in the host crystal. the case of the racemic guests, complexes obtained were analysed using chiral GC-MS. TETROL preferred the R-enantiomers of 2- and 3-methylcyclohexanone (21.7% and 16.7% e.e.). The S-enantiomer of camphor was favoured but the e.e. was low (3.8%). p-AnisylTETROL had a preference for the S-enantiomer in the case of 2- and 3-methylcyclohexanone as well as 2-butanol (44.3%, 20.4% and 1.7% e.e., respectively). p-TolylTETROL could only successfully resolve 2-butanol (23.5% e.e. in favour of the R-enantiomer). o-TolylTETROL preferred the R-enantiomers of methyl phenyl sulfoxide (29.2% e.e.) and 2-butanol (21.5% e.e.). Overall, TETROL and its derivatives exhibited the ability to resolve racemic mixtures to some extent.
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- Date Issued: 2015
The synthesis and analysis of (2R,3R)-1,1,4,4- tetraphenylbutane-1,2,3,4-tetraol (tetrol) and derivatives, and a study of their host potential
- Authors: Weitz, Selwyn Herbert
- Date: 2015
- Subjects: Chemistry, Organic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/3735 , vital:20459
- Description: This investigation focussed on the inclusion and resolution ability of (2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL), studies on the stoichiometry of its derivatives and the formation of inclusion compounds for single crystal analysis. The guest compounds that featured in the main study were cyclohexanone, 2-methylcyclohexanone, 3-methylcyclohexanone and 4-methylcyclohexanone. It was found that 3- and 4-methylcyclohexanone were trapped in their energetically unfavourable axial conformations in the inclusion crystal. Resolution experiments proved that (2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol can be used as a resolving agent for 2- and 3-methylcyclohexanone, with ee values of 13% and 22%, respectively (according to the method of Hiemstra), in favour of the R-enantiomer. Single crystal X-ray diffraction (SCXRD) studies, however, showed that 2-methylcyclohexanone was resolved with an ee of 30% in R. An ee of 56% in R was obtained for 3-methylcyclohexanone. Enantiomer enrichment of 2-methylcyclohexanone was achieved in basic medium (ee of 18% according to the method of Hiemstra) and showed that by using the host in either half or double the molar ratio of the guest, a higher ee was obtained than for a 1:1 ratio. The following TETROL derivatives were also synthesized and their stoichiometries with various guest compounds were determined: (2R,3R)-1,1,4,4-tetra(naphthalen-1-yl)butane-1,2,3,4-tetraol; (2R,3R)-1,1,4,4-tetra(naphthalen-2-yl)butane-1,2,3,4-tetraol; (2R,3R)-1,1,4,4-tetra(p-anisyl)butane-1,2,3,4-tetraol; (2R,3R)-1,1,4,4-tetra(p-tolyl)butane-1,2,3,4-tetraol; (2R,3R)-1,1,4,4-tetra(m-tolyl)butane-1,2,3,4-tetraol and; (2R,3R)-1,1,4,4-tetra(o-tolyl)butane-1,2,3,4-tetraol.
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- Date Issued: 2015
Reactions towards the synthesis of the uncommon P57 cymarose moiety
- Authors: Mahanjana, Lungelwa
- Date: 2013
- Subjects: Chemistry, Organic , Organic compounds -- Synthesis
- Language: English
- Type: Thesis , Masters , MTech
- Identifier: http://hdl.handle.net/10948/6711 , vital:21136
- Description: The work described in this study aims to investigate methods that will improve a lengthy synthetic pathway in the synthesis of the P57 cymarose moiety, and to examine the conformational structure of certain glycosides in order to shed light on the problematic stereochemical issues surrounding the formation of the cymarose glycosyl donor. The cymarose moiety forms part of the trisaccharide derivative present in P57, an appetite suppressant molecule. Modification of reaction steps in the conversion of the stereochemistry at C-3 of a previously reported synthesis of the P57 cymarose moiety was carried out. The first step was the selective oxidation of D-glucal using Pd/C in the presence of acetonitrile. These reaction conditions are more appropriate for the oxidation step to avoid decomposition of the formed molecules. Successive protection of the free OH groups was followed by NaBH4 reduction under stereo-controlled conditions, influenced by CeCl3•7H2O. However, the reduced product could not be isolated from the starting material and this led to ambiguous results when attempting to confirm whether the conversion of the stereochemistry at C-3 had occurred or not. The effect of reaction conditions, such as change in reaction temperature, during the preparation of the cymarose glycosyl donor was studied in order to find suitable reaction conditions to produce α,β-allo derivatives with high stereoselectivity. Compared to the reported synthetic method, this set-up gave improved yields with, unfortunately, similar or slightly lower selectivity to the formation of α-altro:α,β-allo derivative. Examination of the conformational structure of the allal derivative, in order to understand the mechanism at work during the placement of the directing group at C-2, was carried out using molecular modelling. The mechanistic implications of this very short study are discussed and it provides some insights into the likely pathway of the iodination reaction and its selectivity in particular, to the D-allose system.
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- Date Issued: 2013
Solvent-free synthesis of bisferrocenylimines and their coordination to rhodium (I)
- Authors: Kleyi, Phumelele Eldridge
- Date: 2009
- Subjects: Organic compounds -- Synthesis , Organic solvents , Solution (Chemistry) , Chemistry, Organic , Coordination compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10393 , http://hdl.handle.net/10948/1053 , Organic compounds -- Synthesis , Organic solvents , Solution (Chemistry) , Chemistry, Organic , Coordination compounds
- Description: Solvent-free reactions possess advantages compared to the solvent route, such as shorter reaction times, less use of energy, better yields, etc. Herein, the synthesis and characterization of bisferrocenylimines and arylbisamines are described. Reduction of the above compounds with LAH resulted in the formation of bisferrocenylamines and arylbisamines, respectively. The coordination chemistry of all the above compounds to rhodium(I) is also discussed in the prepared complexes [Rh(COD)(NN)]ClO4, where NN = bisferrocenylimines, and [Rh(COD)(NN)]BF4, where NN = bisferrocenylamines and arylbisamines. X-ray crystal structures of the complexes [Rh(COD)(NN)]ClO4 ([3.2] and [3.3]) have been obtained. Complexes of the type [Rh(COD)(NN)]BF4 were characterized with IR and UV-vis spectroscopy, cyclic voltammetry and conductometry. The catalytic activity of the complexes was also investigated: [Rh(COD)(NN)]ClO4 for the polymerization of phenylacetylene and [Rh(COD)(NN)]BF4 for the hydroformylation of styrene.
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- Date Issued: 2009
Chemical studies of necic acid analogues
- 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.
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- Date Issued: 1997
Synthesis and conformational studies of indolizines
- Authors: George, Rosemary
- Date: 1994
- Subjects: Indole alkaloids -- Research , Organic compounds -- Synthesis , Chemistry, Organic
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4367 , http://hdl.handle.net/10962/d1005032 , Indole alkaloids -- Research , Organic compounds -- Synthesis , Chemistry, Organic
- Description: The present investigation has involved a kinetic and mechanistic study of the thermal cyclization of 3-acetoxy-3-(2-pyridyl)-2-methylenepropanoate esters and related compounds to 2-substituted indolizines. Substrates for the kinetic study were prepared via the Baylis-Hillmann reaction of pyridine-2-carboxaldehydes with acrylate esters, acrylonitrile and methyl vinyl ketone. The resulting hydroxy compounds were then acetylated to afford the acetoxy derivatives, thermal cyclization of which gave the corresponding 2-substituted indolizines. The cyclization reactions was followed using 'H NMR spectroscopy and were shown to follow firstorder kinetics. The influence of the various substituents on the observed first-order rate constants has been examined and variable temperature studies have permitted evaluation of activation parameters for the formation of methyl indolizine-2-carboxylate and ethyl indolizine-2-carboxylate. An alternative route to 2-substituted indolizines via halogenated derivatives was explored and several halogenated 2-pyridyl derivatives were synthesised and their thermal cyclization to indolizines was attempted. Novel 5-methylindolizine-2-carboxamides were prepared as part of this investigation and dynamic NMR spectroscopy was used to study internal rotation about the amide N-CO bond in these compounds.
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- Date Issued: 1994
The effects of organic perturbants on the structure of soluble collagen
- Authors: Hart, Geoffrey Joseph
- Date: 1971
- Subjects: Chemistry, Organic , Collagen
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3846 , http://hdl.handle.net/10962/d1012157 , Chemistry, Organic , Collagen
- Description: Organic solvents were used in the present study as a means of investigating the non-covalent interactions involved in the maintenance and pertubation of the three-dimensional structure of the collagen macromolecule in solution. The two main types of non-covalent interaction under consideration are hydrogen bond formation and hydrophobic effects. Elucidation of the relative importance of these factors in the maintenance of the solution structure of proteins is an area of intensive investigation and fundamental significance to biochemistry as a whole. During the past decade, considerable progress has been made towards a clearer understanding of the forces involved, and a number of different theoretical and experimental approaches have emerged. Until about 1960, hydrogen bonding was widely believed to be the dominant non-covalent interaction responsible for the maintenance of secondary and tertiary structure in many proteins. Subsequently, an increasingly important role for apolar (hydrophobic) effects was suggested by a number of authors, and at present there is no satisfactorily definitive interpretation of the available experimental evidence. The current work is based on a comparison of the effects of organic solvents on widely different substrates, namely collagen, cellulose, and the chromatographic reference material, catechin. The chromatographic mobility of catechin on cellulose may be regarded as a phenomenon which is mediated entirely by polar interaction mechanisms. The effects of various organic perturbants and of changing solvent/water ratios are readily interpreted on this basis. In the collagenous systems, however, certain results appear to require the introduction of concepts other than those relating exclusively to polar bonding affinities. The experimental evidence shows that there are cases where the enhancement of the polar interaction potential of solvent/water mixtures, in relation to catechin-cellulose systems, is accompanied by an apparent reduction of polar interaction potential of the same solvent/water mixtures with respect to soluble collagen. The anomaly outlined above will be discussed in terms of two fundamentally different theoretical assumptions. In the first of these, the mechanism of perturbant action in collagenous systems is regarded as essentially similar to that governing catechin-cellulose affinity patterns. Thus, interaction processes are all treated as polar phenomena, in which direct hydrophobic destabilization of the collagen triple helix plays no part. In an attempt to explain the effects of perturbants in both collagen and cellulose-containing systems in terms of the above assumption, two hypotheses are examined involving (1) direct polar interaction between perturbant molecules and functional groups of the protein; (2.) the possibility of an enhanced polar interaction potential of water molecules, due to lowering of the environmental dielectric constant when organic solvents are added to the systems. Within the other broad conceptual division, collagen and cellulose substrates are considered to respond in fundamentally different ways to the action of organic perturbants. As before, cellulose-catechin-solvent interactions are treated as entirely polar phenomena, and perturbant effects interpreted in terms of mechanisms such as direct solvation of the substrate, and the enhanced hydrogen bonding activity of water molecules. In contrast, perturbant lyotropic action with respect to soluble collagen i s viewed as the manifestation of a major contribution by hydrophobic interaction processes to macromolecular stability. Thus, solvents that competitively reduce the assumed entropic contribution to the stability of the collagen triple helix, are seen as potential destabilizers of the native state of the protein and inhibitors of the regeneration of co-operative structures during renaturation. Both of the above approaches are critically assessed in the light of the present work and the dominant trends apparent in the recent literature.
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- Date Issued: 1971