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.
- Full Text:
- Date Issued: 2015
- 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.
- Full Text:
- 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.
- Full Text:
- Date Issued: 2015
- 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.
- Full Text:
- 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.
- Full Text:
- Date Issued: 2013
- 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.
- Full Text:
- 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.
- Full Text:
- Date Issued: 2009
- 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.
- Full Text:
- Date Issued: 2009
Novel camphor derivatives as potential asymmetric alkylation auxiliaries
- Authors: Skiti-Mama, Neliswa
- Date: 2008
- Subjects: Alkylation , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10372 , http://hdl.handle.net/10948/1077 , Alkylation , Chemistry, Organic
- Description: The investigation has been focussed on the synthesis and characterisation of camphor-derived chiral auxiliaries that incorporate two camphor skeletons and an evaluation of their stereodirecting potential in ester α-benzylation reactions. Two regioisomeric camphorquinone-derived monoketals were synthesised and identified by 1D- and 2D-NMR, and X-ray crystallography. The stereo-directing potential of the alcohols that resulted from reduction of these ketones as chiral auxiliaries in the alkylation of carboxylate ester derivatives has been studied. The diastereoselectivities shown by NMR spectroscopy range from 14- 30 % d.e. for (1R,2 S, 3R) -2 ,2-[ (1R, 2 S, 3R) -bornane-2,3-dioxy] - bornan-3-ol and 68-74 % d.e. for (1R, 2S ,3R) -3 ,3-[ (1R, 2S ,3R) - bornane-2, 3 -dioxy]bornan-2-ol with selectivities that correlate with the size of the alkyl group in the ester moiety. Trapping of the enolates generated from (1R, 2S ,3R)-2, 2 -[(1R,2 S, 3R) -bornane- 2,3-dioxy]bornan-3-yl propanoate afforded both E- and Z-silyl ketene acetal derivatives in the ratio of 64:36 confirming the formation of both possible enolate structures during enolization. Chiral auxiliaries containing a hemiaminal ether blocking group as well as two chiral alcohols containing monothio-ketal blocking groups have also been synthesised. α-Benzylation of their corresponding propanoate esters afforded the alkylated product with disappointingly low diastereos electivities. Asymmetric reduction of α-keto esters attached to (1R, 2 S, 3R) - 2,2- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-3-ol and (1R, 2S ,3R) - 3,3- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-2-ol with metal hydrides proceeded with selectivities of up to 30 % d.e. Modelling of the keto ester derivatives at DFT levels provided useful insights into possible conformations adopted by the two α-keto esters and hence the preferred face of attack by metal hydride during reduction.
- Full Text:
- Date Issued: 2008
- Authors: Skiti-Mama, Neliswa
- Date: 2008
- Subjects: Alkylation , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10372 , http://hdl.handle.net/10948/1077 , Alkylation , Chemistry, Organic
- Description: The investigation has been focussed on the synthesis and characterisation of camphor-derived chiral auxiliaries that incorporate two camphor skeletons and an evaluation of their stereodirecting potential in ester α-benzylation reactions. Two regioisomeric camphorquinone-derived monoketals were synthesised and identified by 1D- and 2D-NMR, and X-ray crystallography. The stereo-directing potential of the alcohols that resulted from reduction of these ketones as chiral auxiliaries in the alkylation of carboxylate ester derivatives has been studied. The diastereoselectivities shown by NMR spectroscopy range from 14- 30 % d.e. for (1R,2 S, 3R) -2 ,2-[ (1R, 2 S, 3R) -bornane-2,3-dioxy] - bornan-3-ol and 68-74 % d.e. for (1R, 2S ,3R) -3 ,3-[ (1R, 2S ,3R) - bornane-2, 3 -dioxy]bornan-2-ol with selectivities that correlate with the size of the alkyl group in the ester moiety. Trapping of the enolates generated from (1R, 2S ,3R)-2, 2 -[(1R,2 S, 3R) -bornane- 2,3-dioxy]bornan-3-yl propanoate afforded both E- and Z-silyl ketene acetal derivatives in the ratio of 64:36 confirming the formation of both possible enolate structures during enolization. Chiral auxiliaries containing a hemiaminal ether blocking group as well as two chiral alcohols containing monothio-ketal blocking groups have also been synthesised. α-Benzylation of their corresponding propanoate esters afforded the alkylated product with disappointingly low diastereos electivities. Asymmetric reduction of α-keto esters attached to (1R, 2 S, 3R) - 2,2- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-3-ol and (1R, 2S ,3R) - 3,3- [ (1R,2 S, 3R) -bornane-2, 3 -dioxy]bornan-2-ol with metal hydrides proceeded with selectivities of up to 30 % d.e. Modelling of the keto ester derivatives at DFT levels provided useful insights into possible conformations adopted by the two α-keto esters and hence the preferred face of attack by metal hydride during reduction.
- Full Text:
- Date Issued: 2008
Practical and scalable synthesis of N-Alkyl-N,N'Diacylhydrazines
- Authors: Gouws, Melissa Claire
- Date: 2008
- Subjects: Chemistry, Organic , Acylation , Insecticides
- Language: English
- Type: Thesis , Doctoral , DTech
- Identifier: vital:10406 , http://hdl.handle.net/10948/696 , Chemistry, Organic , Acylation , Insecticides
- Description: The work presented in this thesis is concerned with the evaluation of potential synthetic routes for the diacylhydrazine group of compounds, and particularly, unsymmetrical diacylhydrazines. Diacylhydrazines form the basis for a relatively new group of insecticides that have molt accelerating properties, and which are considered to offer substantial advantages over other insecticides used for the control of certain insects. The overall objective for this study is to evaluate different potential synthetic routes for a model diacylhydrazine with the view to define potentially scaleable routes. The compound selected for this study was the unsymmetrical diacylhydrazine, N-[N-(tertbutyl) phenylcarbonylamino](4-methylphenyl)-carboxamide since it offers the same range of challenges that would be expected for the synthesis of other similar unsymmetrical diacylhydrazines. Thus, the synthesis of unsymmetrical diacylhydrazines require two reaction steps: The first step is the synthesis of the intermediate mono-acylhydrazine, while the second step is the synthesis of the desired diacylhydrazine from the intermediate mono-acylhydrazine. The most important factor in the two-step reaction sequence is to obtain a high degree of selectivity for the desired mono-acylhydrazine isomer. Acylation of t-butylhydrazine using 4-methylbenzoyl chloride can produce the desired product N-[(tert-butyl)amino](4-methylphenyl)carboxamide in yields above 90 percent, but this reaction produces a variety of by-products, including the “wrong” isomer (N-amino-N- (tert-butyl)(4-methylphenyl)carboximide). Unexpected byproducts for this particular acylation reaction, not previously reported in the literature have also been identified during this investigation. This includes a de-butylated diacylhydrazine, (4-methylphenyl)- N-[(4-methylphenyl)carbonylamino] carboxamide. Although the reaction between tert-butylhydrazine and 4-methylbenzaldehyde is very selective giving near quantitative yields of the desired hydrazone, the subsequent conversion of the hydrazone into the desired mono-acylhydrazine is problematic. The most promising route appears via bromination to form the hydrazidic bromide, followed by hydrolysis of the hydrazidic bromide. Yields for the bromination reaction during this investigation were somewhat higher than that reported previously in literature. Hydrolysis of the hydrazidic bromide, apparently also results in the hydrolysis of the reaction product to give an ester of the free acid (when an ester solvent is used). The synthesis of N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide was only briefly considered to evaluate essentially two approaches, namely: · The conversion of the monoacylhydrazine, N-[(tert-butyl)amino](4- methylphenyl)carboxamide, by acylating with either benzoyl chloride or methylbenzoate (gave 86 percent N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide when benzoyl chloride was used as acylating agent); and · The one-pot conversion of the hydrazone, [(1E)-2-(4-methylphenyl)-1- azavinyl](tert-butyl)]amine, by bromination/hydrolysis and acylation. In this case, benzoyl chloride (2 percent N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide), benzoic acid (80.67 percent N-[N-(tertbutyl) phenylcarbonylamino](4-methylphenyl)carboxamide) were evaluated as potential acylating agents.
- Full Text:
- Date Issued: 2008
- Authors: Gouws, Melissa Claire
- Date: 2008
- Subjects: Chemistry, Organic , Acylation , Insecticides
- Language: English
- Type: Thesis , Doctoral , DTech
- Identifier: vital:10406 , http://hdl.handle.net/10948/696 , Chemistry, Organic , Acylation , Insecticides
- Description: The work presented in this thesis is concerned with the evaluation of potential synthetic routes for the diacylhydrazine group of compounds, and particularly, unsymmetrical diacylhydrazines. Diacylhydrazines form the basis for a relatively new group of insecticides that have molt accelerating properties, and which are considered to offer substantial advantages over other insecticides used for the control of certain insects. The overall objective for this study is to evaluate different potential synthetic routes for a model diacylhydrazine with the view to define potentially scaleable routes. The compound selected for this study was the unsymmetrical diacylhydrazine, N-[N-(tertbutyl) phenylcarbonylamino](4-methylphenyl)-carboxamide since it offers the same range of challenges that would be expected for the synthesis of other similar unsymmetrical diacylhydrazines. Thus, the synthesis of unsymmetrical diacylhydrazines require two reaction steps: The first step is the synthesis of the intermediate mono-acylhydrazine, while the second step is the synthesis of the desired diacylhydrazine from the intermediate mono-acylhydrazine. The most important factor in the two-step reaction sequence is to obtain a high degree of selectivity for the desired mono-acylhydrazine isomer. Acylation of t-butylhydrazine using 4-methylbenzoyl chloride can produce the desired product N-[(tert-butyl)amino](4-methylphenyl)carboxamide in yields above 90 percent, but this reaction produces a variety of by-products, including the “wrong” isomer (N-amino-N- (tert-butyl)(4-methylphenyl)carboximide). Unexpected byproducts for this particular acylation reaction, not previously reported in the literature have also been identified during this investigation. This includes a de-butylated diacylhydrazine, (4-methylphenyl)- N-[(4-methylphenyl)carbonylamino] carboxamide. Although the reaction between tert-butylhydrazine and 4-methylbenzaldehyde is very selective giving near quantitative yields of the desired hydrazone, the subsequent conversion of the hydrazone into the desired mono-acylhydrazine is problematic. The most promising route appears via bromination to form the hydrazidic bromide, followed by hydrolysis of the hydrazidic bromide. Yields for the bromination reaction during this investigation were somewhat higher than that reported previously in literature. Hydrolysis of the hydrazidic bromide, apparently also results in the hydrolysis of the reaction product to give an ester of the free acid (when an ester solvent is used). The synthesis of N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide was only briefly considered to evaluate essentially two approaches, namely: · The conversion of the monoacylhydrazine, N-[(tert-butyl)amino](4- methylphenyl)carboxamide, by acylating with either benzoyl chloride or methylbenzoate (gave 86 percent N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide when benzoyl chloride was used as acylating agent); and · The one-pot conversion of the hydrazone, [(1E)-2-(4-methylphenyl)-1- azavinyl](tert-butyl)]amine, by bromination/hydrolysis and acylation. In this case, benzoyl chloride (2 percent N-[N-(tert-butyl)phenylcarbonylamino](4-methyl phenyl)carboxamide), benzoic acid (80.67 percent N-[N-(tertbutyl) phenylcarbonylamino](4-methylphenyl)carboxamide) were evaluated as potential acylating agents.
- Full Text:
- Date Issued: 2008
Synthesis, properties and reactions of Novel Quinone Methides
- Authors: Taljaard, Jana Heloïse
- Date: 2007
- Subjects: Quinone , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10408 , http://hdl.handle.net/10948/616 , Quinone , Chemistry, Organic
- Description: Novel p-quinone methides have been synthesized by the dealkylation of 5-(p-alkyloxyaryl)- 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ols and related compounds. Aspects of the dealkylation reaction were investigated using computational methods in order to identify possible intermediates and postulate reasons for the observed reactivity patterns. This included studying the effect of varying the size of the central B-ring, changing the alkyloxy group, and altering the substitution pattern on the parent alcohols. We have assessed the relative energies of reaction intermediates and have also evaluated the influence of factors such as charge delocalisation, LUMO properties of the carbocations and thermodynamic factors on the dealkylation reaction. The use of different dealkylating reagents was also briefly investigated. Demethylation of 1,3- dimethyl-11-(4-methoxyphenyl)-6,11-dihydrodibenzo[b,e]oxepin-11-ol with pyridine hydrochloride led to acid-catalyzed ring-contraction of the parent alcohol to form a novel substituted anthraquinone, 9-(4-hydroxyphenyl)-1,3-dimethyl-anthracen-10-(9H)-one, in good yield. The general reactivity of the p-quinone methides of interest to us was explored by subjecting these compounds to reaction with a range of nucleophiles (bases, Grignard reagents and alcohols). A range of aryl Grignard reagents were reacted with the p-quinone methides, with the main product isolated in almost all cases being the aryl-coupled 1,2-addition product. The nucleophilic addition reactions of alcohols were supported by a computational study and a probable reaction mechanism has been postulated. A base-catalyzed rearrangement is proposed to account for the formation of products in which dehydrogenation of the ethane bridge was observed. These studies showed that in these p-quinone methides, chemical reactivity is strongly influenced by steric crowding, resulting in reversal of the normal 1,2- vs. 1,6- selectivities expected for nucleophilic addition. The ketalization process was explored further using diols and thiols. Products analogous to those obtained with the monohydric alcohols resulted from the diols, along with a series of novel bis-ethers. A range of miscellaneous reactions of 4-(dibenzo[a,d]cycloheptan-5-ylidene)cyclohexa-2,5,- dienone and related systems were investigated. Functionalization by epoxidation, dichlorocarbenation and Diels-Alder reactions, photochemical and [2+2] cycloaddition were attempted and reduction and oxidation reactions were also explored. Photochemical demethylation of an ortho-methoxyl substituent on the p-quinone methide system was observed to occur in good yield. The p-quinone methides underwent reductive coupling in the presence of Zn/AlCl3. The electronic spectra of highly conjugated carbocations were obtained and their potential as novel dyes evaluated. A low-temperature Grignard exchange reaction followed by spontaneous cyclization upon workup, was successful in synthesizing the lactone, spiro[10,11- dihydro-5H-dibenzo[a,d]cyclohepten-(3’,4’H)-phenyl-5,2’(5’H)-furan-5’-one], in one step from the starting ketone. A novel seven-membered Malachite Green dye analogue, 11-(4- dimethylamino-phenyl)-3-morpholin-4-yl-6,11-dihydro-dibenzo[b,e]oxepin-11-ol, was also synthesized and its electronic spectra compared to that of the unannulated Malachite Green dye series. All novel compounds synthesized were characterized using NMR, IR and HRMS-analysis.
- Full Text:
- Date Issued: 2007
- Authors: Taljaard, Jana Heloïse
- Date: 2007
- Subjects: Quinone , Chemistry, Organic
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10408 , http://hdl.handle.net/10948/616 , Quinone , Chemistry, Organic
- Description: Novel p-quinone methides have been synthesized by the dealkylation of 5-(p-alkyloxyaryl)- 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ols and related compounds. Aspects of the dealkylation reaction were investigated using computational methods in order to identify possible intermediates and postulate reasons for the observed reactivity patterns. This included studying the effect of varying the size of the central B-ring, changing the alkyloxy group, and altering the substitution pattern on the parent alcohols. We have assessed the relative energies of reaction intermediates and have also evaluated the influence of factors such as charge delocalisation, LUMO properties of the carbocations and thermodynamic factors on the dealkylation reaction. The use of different dealkylating reagents was also briefly investigated. Demethylation of 1,3- dimethyl-11-(4-methoxyphenyl)-6,11-dihydrodibenzo[b,e]oxepin-11-ol with pyridine hydrochloride led to acid-catalyzed ring-contraction of the parent alcohol to form a novel substituted anthraquinone, 9-(4-hydroxyphenyl)-1,3-dimethyl-anthracen-10-(9H)-one, in good yield. The general reactivity of the p-quinone methides of interest to us was explored by subjecting these compounds to reaction with a range of nucleophiles (bases, Grignard reagents and alcohols). A range of aryl Grignard reagents were reacted with the p-quinone methides, with the main product isolated in almost all cases being the aryl-coupled 1,2-addition product. The nucleophilic addition reactions of alcohols were supported by a computational study and a probable reaction mechanism has been postulated. A base-catalyzed rearrangement is proposed to account for the formation of products in which dehydrogenation of the ethane bridge was observed. These studies showed that in these p-quinone methides, chemical reactivity is strongly influenced by steric crowding, resulting in reversal of the normal 1,2- vs. 1,6- selectivities expected for nucleophilic addition. The ketalization process was explored further using diols and thiols. Products analogous to those obtained with the monohydric alcohols resulted from the diols, along with a series of novel bis-ethers. A range of miscellaneous reactions of 4-(dibenzo[a,d]cycloheptan-5-ylidene)cyclohexa-2,5,- dienone and related systems were investigated. Functionalization by epoxidation, dichlorocarbenation and Diels-Alder reactions, photochemical and [2+2] cycloaddition were attempted and reduction and oxidation reactions were also explored. Photochemical demethylation of an ortho-methoxyl substituent on the p-quinone methide system was observed to occur in good yield. The p-quinone methides underwent reductive coupling in the presence of Zn/AlCl3. The electronic spectra of highly conjugated carbocations were obtained and their potential as novel dyes evaluated. A low-temperature Grignard exchange reaction followed by spontaneous cyclization upon workup, was successful in synthesizing the lactone, spiro[10,11- dihydro-5H-dibenzo[a,d]cyclohepten-(3’,4’H)-phenyl-5,2’(5’H)-furan-5’-one], in one step from the starting ketone. A novel seven-membered Malachite Green dye analogue, 11-(4- dimethylamino-phenyl)-3-morpholin-4-yl-6,11-dihydro-dibenzo[b,e]oxepin-11-ol, was also synthesized and its electronic spectra compared to that of the unannulated Malachite Green dye series. All novel compounds synthesized were characterized using NMR, IR and HRMS-analysis.
- Full Text:
- Date Issued: 2007
- «
- ‹
- 1
- ›
- »