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
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