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Item Open Access Amphiphile-coated magnetic iron oxide nanoparticles for the extraction of contaminants from the aqueous media(University of the Free State, 2023) Mzinjani, Viwe; Azov, V. A; Langner, E. H. G.The availability of clean water to the community/ society is becoming a huge problem for its ecosystem. These toxic contaminants come from surface and subsurface water systems such as dams, rivers, and oceans that are eluted from industrial, domestic, agricultural, and recreational activities. Both organic and inorganic contaminants are found in these water systems in high concentrations, which put aquatic life at tremendous risk and the environment in general. Thus, the need for synthetic materials that can be used to solve this ongoing problem of water contamination is becoming an obvious research goal that needs urgent attention. Nanomaterials such as nanoparticles are currently being investigated as a tool to remove various contaminants in wastewater. Nanoparticles are very small particles with sizes ranging from 1 to 100 nm. Depending on their type, these nanomaterials may demonstrate various unique properties, such as strong catalytic activity, superparamagnetism, quantum confinement, and extremely high surface-to-volume ratios. In this project, the high surface-to-volume property was explored during the adsorption of methylene blue dye in spiked water samples. Magnetic iron oxide nanoparticles were chosen because of their magnetic susceptibility and most availability of iron metal on earth, making them cheaper materials since they can be prepared from cheap iron precursors. Magnetite NPs were prepared using the co-precipitation method, where iron precursors of Fe²⁺ and Fe³⁺ were dissolved in de-ionized water and ammonium hydroxide was used as the precipitating agent under an inert atmosphere. Better adsorption capacities of these nanoparticles can be achieved by functionalizing them with different organic and inorganic molecules. In this study, mono-alkyl phosphate esters of varying alkyl chain lengths were synthesized and used to functionalize the as-synthesized magnetite NPs to render better affinity towards organic dyes (Figure 1). The as-prepared magnetite NPs were characterized using techniques such as TEM, SEM, FTIR, EDS, and PXRD, and the organic functionalization molecules were characterized using NMR (¹H, ¹³C, and ³¹P), FTIR, and mass spectrometry. These characterization techniques confirmed the successful synthesis of the nanoparticles and mono-alkyl phosphate esters of varying alkyl chain lengths. TEM and SEM micrographs showed close to spherical shapes of the prepared nanoparticles with particle diameters ranging from 12 – 16 nm for bare Fe₃O₄ NPs and 17 – 22 nm for functionalized NPs. Comparable particle size was also obtained from the PXRD results using the Scherrer equation (eq. 3.1) where a particle size of 13 nm was obtained. PXRD characteristic peaks confirmed the inverse spinel structure of the Fe₃O₄ NPs. The presence of iron (Fe) and oxygen (O) in the EDS results confirmed the formation of the magnetite nanoparticles and the presence of carbon (C) and phosphorus (P) on the coated nanoparticles confirmed the successful coating of the Fe₃O₄ NPs. FTIR, NMR, and MS results showed comparable results to those found in the literature.Item Open Access Application of the cross-metathesis reaction as alternative methodology for the synthesis of paramethoxycinnamate analogues as sunscreen components(University of the Free State, 2016-01) Swart, Marthinus Rudi; Marais, C.; Bezuidenhoudt, B. C. B.2-Ethylhexyl p-methoxycinnamate [Octyl methoxycinnamate (OMC)] is an organic compound that is commercially used in the cosmetic industry as a UV blocker in sunscreen creams and lotions. Commercial production of this compound, however, is hampered by multiple synthetic steps, high temperatures, tedious work-up procedures, halogenated by-products, and low atom economy. Due to the abundance of naturally occurring essential-oil phenylpropenoids like estragole, eugenol, and safrole, which can easily be transformed into anethole, isoeugenol, and isosafrole by catalytic double bond isomerisation, the possibility of utilizing one of these b-methylstyrenes, i.e. anethole, together with 2-ethylhexyl acrylate in metathesis based methodology for the preparation of OMC looked promising and was investigated. Model metathesis reactions between trans-b-methylstyrene and methyl acrylate over Grubbs 2nd generation catalyst, however, produced only the homometathesis product, trans-stilbene, in very high yields (>99%). Solvent, temperature and reactant ratio studies failed to change the course of the reaction towards the desired cross-metathesis product. Since Forman et al. reported the addition of phenol to the reaction mixture to enhance crossmetathesis over self-metathesis, the reaction was repeated with p-cresol (2 eq.) as additive. In order to prevent secondary metathesis reactions from occurring, the propene side-product was also stripped away by entrainment with argon, which led to the successful formation of methyl cinnamate in 38% yield. In order to determine the general applicability of the new process, the electronic effect, if any, of substituents in the para-position of the b-methylstyrene and the steric/electronic influence of the alkyl group attached to the α,b-unsaturated carbonyl compound on the outcome of the reaction were investigated. Trans-pmethoxy- b-methylstyrene (trans-anethole) (1 eq.) and trans-4- trifluoromethylsulfonyloxy-b-methylstyrene (1 eq.) were therefore reacted with methyl acrylate (2 eq.) under the optimized reaction conditions [Grubbs 2nd generation catalyst (0.5 mol%), p-cresol (0.25 eq.), refluxing DCM (10 mL), 2 hours] and it was found that an electron-donating group in the para-position caused a slight decrease in cross-metathesis product formation (36% vs 38% for unsubstituted trans-b-methylstyrene) whereas an electron-withdrawing group (triflate) in the same position enhanced cinnamate formation (43% vs 38%). The concomitant homo-metathesis reaction followed the opposite trend with the p-triflate suppressing stilbene formation (4% vs 18% for unsubstituted trans-b- methylstyrene) and a p-methoxy group enhancing the formation of the stilbene (50% vs 18%). When the influence of the O-alkyl group attached to the α,b-unsaturated carbonyl moiety was investigated, it was found that the yield of the cinnamate product increased with increasing steric bulk of the alkyl group. For the reaction of unsubstituted trans-b-methylstyrene with methyl acrylate and n-butyl acrylate, respectively, the yield increased from 38 to 55%, while for reaction between trans-anethole and these acrylates it went from 36 to 41%. Substituting the ester O-alkyl moiety in the α,b-unsaturated system with an alkyl group (3-buten- 2-one) and a hydrogen (acrolein), resulted in moderate yields of 34 and 32% for the reactions between the ketone and unsubstituted trans-b-methylstyrene and trans-anethole, respectively, while with acrolein only trace amounts (< 5%) of the cross–metathesis products were obtained. In all these reactions, the respective stilbenes were formed in 18 (for the reaction between methyl or nbutyl acrylate and trans-b-methylstyrene) to 58% (for the reaction of acrolein with trans-b-methylstyrene) yield. Finally, trans-β-methylstyrene and transanethole were reacted with 2-ethylhexyl acrylate to form 2-ethylhexyl cinnamate and the desired 2-ethylhexyl p-methoxycinnamate (OMC), which could be isolated as major products from the reaction in 64 and 47% yields, respectively. Due to the higher reactivity of trans-anethole, the cross-metathesis product (OMC) in this instance was accompanied by 32% of 4,4’-dimethoxystilbene. In an effort to determine how p-cresol addition affects the catalytic cycle of Grubbs 2nd generation catalyst and thus how it influences product formation, a full NMR study of the addition of cresol to the catalyst, the catalyst and trans-b-methylstyrene, the catalyst and methyl acrylate, as well as all the reactants together, was embarked upon. Despite severely restricted rotation, which necessitated the spectra to be recorded at 60 oC, room temp., and -40 oC, all the 1H and 13C NMR resonances in the spectra of the Grubbs II catalyst could be allocated unambiguously to the appropriate protons and carbon atoms. 31P NMR studies allowed for the confirmation of a hydrogen bonding complex between cresol and the catalyst, while it also indicated some dissociation of the tricyclohexylphosphine from the catalyst to occur. The liberated tricyclohexylphosphine, however, prefers to react with the acrylate in a 1,4- addition process rather than forming a complex with the cresol as was postulated by Forman et al. This was confirmed by the preparation of the zwitterionic phosphonium salt through reaction of tricyclohexylphosphine with methyl acrylate in the presence of LiCl. Addition of cresol to the reaction mixture enhances the formation of the salt in its protonated form, while it also induces accelerated formation of oligomeric forms of the initially formed monomeric zwitterionic phosphonium salt. Although Forman et al. proposed the addition of phenols to stabilize the Grubbs catalyst by slowing down the dissociation of the tricyclohexylphosphine from the metal and once dissociated, prevents the phosphine from binding to the metal again, this explanation does not allow for the fact that the more reactive styrene analogue becomes less reactive than the acrylate moiety when cresol is added to the reaction mixture, as is evident from the fact that cresol addition enhances cross-metathesis. It was determined during the current study that the crossmetathesis products (cinnamates) are indeed the result of the primary metathesis process and are not formed through secondary metathesis of the stilbene products. In order to explain the formation of the cross-metathesis over homo-metathesis products in the presence of cresol, it is proposed that an associative mechanism rather than a dissociative process is prevailing when cresol is added to the reaction mixture. In this instance the co-ordination number of the ruthenium temporarily increases from 5 to 6 to allow for the additional ligand to be attached to the metal centre. The catalyst complex therefore becomes sterically more crowded and the steric size of the incoming ligand (reactant) would play a decisive role in its ability to react with the metal centre in the first step of the reaction. Since acrylate represents a mono substituted alkene and the alkyl group resides in a remote location with regard to the reaction centre, it would be sterically less demanding when compared to trans-b-methylstyrene and lead to enhanced formation of the cross-metathesis product. This assumption was proven by substituting methyl acrylate with methyl crotonate during the reaction and the resulting drop in cross-metathesis product from 38 to 31% yield observed. Support for this proposal comes from results by Fogg and co-workers, who reported cross-metathesis to be the dominant reaction when b-methylstyrenes were reacted with acrylates over the Hoveyda-Grubbs catalyst. Finally, with a number of cinnamates (OMC, methyl p-methoxycinnamate, methyl cinnamate, n-butyl cinnamate, n-butyl p-methoxycinnamate, and 2- ethylhexyl cinnamate) and 3-buten-2-ones [4-phenyl-3-buten-2-one and 4-(4- methoxyphenyl)-3-buten-2-one] available, it was decided to evaluate the UV-B blocking properties of these compounds through utilization of UV spectroscopy in an effort to determine if OMC would, in principle, be the best sunscreen component of the series. By comparing the UV spectra of OMC to that of the other compounds, it was determined that methyl cinnamate, n-butyl cinnamate, methyl p-methoxycinnamate and n-butyl p-methoxycinnamate could be promising candidates in the development of new and maybe better sunscreen lotions and should be subjected to biological evaluation processes.Item Open Access Atropisomerie in nuwe tipe bifeniel en o-terfeniel gekondenseerde tanniene(University of the Free State, 1984-03) Young, Esme; Ferreira, D.; Roux, D. G.Afrikaans: Chemiese ondersoek van die kernhout van Prosopis gZanduZosa het aan die lig gebring dat dit oor 'n komplekse flavanoïedinhoud beskik. As gevolg van hierdie kompleksiteit, was genoegsame materiaal en 'n aantal goedbeplande skeidingstegnieke van fundamentele belang. Die oorheersende fenoliese komponent van die kernhout is 'n flavan-3-ol met 'n 3' ,4' ,7,8-tetrahidroksi fenoliese substitusiepatroon. Dit dien as voorganger vir 'n verskeidenheid komplekse metaboliese analoë. Die ooreenstemmende flavan-3,4-diol met 'n soortgelyke substitusiepatroon, is slegs in spoorhoeveelhede geïsoleer. Afgesien van die isolasie van "konvensioneel" gekoppelde biflavanoïede gebaseer op elektrofiele aanval by die C4-karbeniumioon vanaf flavan-3,4-diole op die nukleofiele posisies van flavan-3-ole, is 'n nuwe 1-flavaniel-1,3- diarielpropan-2-ol sowel as 'n B-ring gekoppelde flavaniel-2-bensoïelbnsofuraan geïsoleer. Die uniekheid van hierdie ondersoek is egter gasetel in die identifisering van [5,6]-gekoppelde en atropisomeriese l5,51-biflavanoïede gebaseer op 'n bifenielbinding wat na triflavanoïedvlak uitgebrei is met herkenning van vier [5,5:5,6]-o-terfeniel triflavanoïedatropisomere. Die [5,5]-atropisomere is reeds op vryfenoliese vlak skeibeer- terwyl die [5,6]-isomeer en [5,5:5,6]-o-terfeniel atropisomere eers na derivatisering geskei kan word. Die 1H kmr-spektra van hierdie 5,5 -dimere en [5,5:5,6]-trimere vertoon opvallend skerp spektra by kamertemperatuur wat op "starheid" van struktuur by hierdie temperature dui. Hierdie spektra vertoon nie wesenlike verskerping van resonanse by hoër temperature nie. Verdere getuienis vir atropisomere by die [5,5]-gekoppelde dimere is aan die hand van 'n isomerisasie eksperiment verkry. Wanneer die temperatuur genoegsaam verhoog word (170'C in DMSO-oplossing), word die twee strukture onderling omskakelbaar. Die verskynsel word toegeskryf aan onderlinge interaksie tussen die "starre" C4-metileenfunksie en die "buttressing" effek van die meta hidroksi- of metoksisubstituent op die CG-proton. By die [5,6]-gekoppelde isomere, word 'n dinamiese ewewig by die 1H kmr-spektra van die metieleterasetaatderivate bespeur. Die 7-0H (D-ring) van die biflavanoied is traag om metilering te ondergaan as gevolg van sterk waterstofbinding met die π-elektrone van die A-ring. Daar word dus gepostuleer dat atropisomere as gevolg van waterstofbinding in die vryfenoliese toestand van die [5,6]-biflavanoied voorkom. Derivatisering hef hierdie waterstofbinding op en gee aanleiding tot 500 MHz kmr-spektra waarin seinverdubbeling en dus 'n redelike mate van beperking op die rotasiespoed voorkom. Sintese van die opties rein [5,6]-biflavanoied met 3' ,4',7,8- tetrahidroksileringspatroon is uitgevoer deur reduksie van (+/-)-3' ,4' ,7,B-tetrametoksidihidroflavonol, kondensasie daarvan aan die monomeriese (+)-3' ,4' ,7,B-tetrahidroksiflavan-3-ol en daaropvolgende skeiding van die diastereoisomeriese mengsel. Tydens suurkondensasie van (+)-mollisacacidien met die 3' ,4' ,7,B-tetrahidroksiflavan-3-oL is beide [4,6] +cis een [4,6] -trans biflavanoiede in die verhouding 1:6.4 verkry. Hierdie verbindings word vergesél deur 'n nuwe "lineêre" trimeer' {[4,6:4,6] -2,3-trans-3,4-trans:2' ,3'-trans:2",3"-trans-3",4"-cis-triflavanoied} wat ontstaan deur kondensasie van die gevormde [4,6]-3,4-trans-biflavanoied as nukleofiel met 'n verdere molekuul flavan-3,4-diol.Item Open Access The characterisation and kinetic study of rhodium(I) and iridium(I) triazole complexes(University of the Free State, 2000-11) Muller, Alfred Johannes; Basson, S. S.; Purcell, W.English: A number of triazolecyclooctadienemetal(l) complexes of the type [M(LL')(cod)] (where M = Ir or Rh and LL' represents the different bidentate N-N'- donor atom ligands, such as bpt-Nl+ and bpt) as well as their oxidative addition products [M(LL')(cod)(Me)(I)] have been prepared and characterised by IR, ¹H NMR and elemental analyses. It was found that in general these complexes are monomeric containing one LL' and cod ligand respectively. The oxidative addition between CH31 and the studied metal(l) complexes have been investigated on a UVNis . spectrophotometer. Under pseudo-first order conditions linear relationships were found indicating second order kinetics. All of the kinetic data had zero intercepts (within experimental error) indicating that no reverse reactions occur. The reactions were carried out in different solvents to study the influence of solvent properties on the reaction rate. The reactions were also conducted at different temperatures to calculate the activation parameters. These indicated an associative mechanism as what is usually expected from these types of complexes. The ability of the LL' bidentate ligands to increase the Lewis basicity of the metal center are reflected in the values of the second order rate constants. From this we can compile the following series indicating the different bidentate ligands' donating capabilities: macsm> AnMetha > hpt > bpt-Nl+ > sacac> tfaa > cupf > bpt' The activation ability of the bpt-Nl+ ligand for oxidative addition to the metal center is better than that of the bpt ligand given the correct solvent and metal center are chosen. It seems that in the case of the [M(bpt-NH)( cod)] complexes the rhodium analogue is more reactive, while the opposite case' is observed for the- [M(bpt)(cod)] complexes. Thus the bpt-Nl+ ligand is the better 0- donor in the rhodium complex, while the bpt ligand is the better 0- donor in the iridium complex.Item Open Access Chemical analysis and evaluation of a homemade pest control mixture used by a local farmer from Maloti-A-Phofung municipality of the Afromontane region in the Free State(University of the Free State, 2022) Sebotsa, Maria Mojabeng; Molefe, N. F.; Mosoabisane, M. F. T.The indigenous community of the Afromontane region has developed and adopted strategies for survival to reduce diseases and eliminate ticks and pests on crops at a lower cost. Biopesticides are efficient in eradicating various plant pests, affordable, quickly biodegradable, with multiple mechanisms of action, freely available supplies, and low toxicity to non-target organisms. The phytochemical composition of different plants is thought to be responsible for their various modes of action. Synthetic pesticides are expensive for small-scale farmers in undeveloped regions like the Afromontane region. Investigating agrochemical alternatives will benefit small-scale farmers who cannot access these due to their high cost. This study aims to analyse and evaluate the effectiveness of homemade pest control used by a small-scale farmer in the Afromontane region. The homemade pest control mixture used by local farmers was collected, then sequentially extracted and sonicated using hexane, chloroform, ethyl acetate, methanol and water. The extracts were screened for active compounds by phytochemical analysis and characterized using ultraviolet-visible (UV-Vis) spectroscopy, Fourier-Transform Infrared Spectroscopy (FTIR), and liquid chromatography-tandem mass spectrometry (LC-MS/MS. Biological testing was used to examine for antibacterial and antifungal activities. Saponins, phenolic compounds, and terpenes were found in all of the extracts after phytochemical analysis of the samples. Through using FTIR spectroscopy, the functional groups of the extracts were detected while UV/Vis spectroscopy identified the presence of chromophore at a region of 220-300 nm. LCMS/MS was performed to dereplicate the analyte components with a focus on their collision induced dissociation (CID) spectra. LC-MS/MS and molecular networking enabled annotation of metabolites active in the different extracts of the homemade pesticide. Based on the connectivity of the molecular network, the homemade pest control molecular networking nodes were grouped into five clusters (1–5). Cluster 1 consists of features annotated as flavonoids, cluster 2 corresponds to compounds of the alkaloids and flavonoids, cluster 3 corresponds to amino acids and alkaloids, cluster 4 consists of fatty acids and alkaloids and cluster 5 consists of features annotated as isoflavonoids. The annotated compounds exhibited various characteristics; some were insecticidal, while others showed antimicrobial activities. The antibacterial and antifungal properties of the sequential and ultrasonic extracts were examined using microdilution. Among the tested extracts, chloroform sequentially and sonicated extracts, methanol sequentially and sonicated extracts showed the best antibacterial activity with the MIC values of 0.09-0.195 mg/ml. The antibacterial activity for sequential chloroform extract showed the best activity against all the bacterial strains, with MIC values ranging between 0.098-0.39 mg/ml. Most of the extracts tested were ineffective against the fungal strains for antimitotic activity. Only a sonicated methanol extract showed the best antifungal activity. The sonicated methanol extract showed good activity (0.39-0.78 mg/ml) against Candida albicans, C. vulgaris and Trichophyton mucoides. In the case of water extracts, no activity was observed in the gram-negative bacteria and antifungal activity. The growth of Fusarium culmorum was suppressed by the sequence water extract and sonicated hexane extract. The current study's phytochemical and annotated compounds revealed that homemade pest-control bioactive compounds such as saponins, terpenoids, alkaloids, isoflavonoids and amino acids have antimicrobial properties against a variety of pathogens. Overall, the findings indicate that the mixture contains phytoconstituents that are effective against plant pathogens and capable of killing insect pests.Item Open Access Chemical profile of walnuts (Juglans regia L.) and synthesis of stilbenes from Arformosia elata(University of the Free State, 2007-01) Sonopo, Molahlehi Samuel; Kamara, B. I.; Bezuidenhoudt, B. C. B.Firstly, this study presents an in-depth investigation on Walnuts (the nuts of Juglans regia L.). Walnuts (Juglans regia L.) are members of the relatively small Juglandaceae family, which have shown positive results in humans, in the treatment of metabolic syndrome. Besides the very high content of unsaturated fatty acids (60-70%) in Walnuts (Juglans regia L.), previous investigations have revealed tannins as the only phenolics present. Generally, plants have had their biological activities attributed to the presence phenolics, specifically the flavonoids, which are the most abundant polyphenols in nature. Since Walnuts leave behind an astringent taste in the mouth after ingestion, a characteristic associated with presence of phenolics, especially tannins, it was reasonable to assume that Walnuts may also contain flavonoids. Besides having well-established biological activities such as, antioxidant, anticancer, and anti-inflammatory properties, flavonoids are believed to augment the ability of Walnuts to act as a possible candidate for treatment of metabolic syndrome. In the previous studies, isolation of flavonoids has not been reported. Therefore, in this study we carried out an in-depth investigation to establish the presence of flavonoids in the Walnuts Juglans regia L. Pure compounds were obtained after repeated column and preparative thin layer chromatography and characterized by extensive NMR spectroscopic methods. The phenolics isolated in this study as peracetate and permethyl derivatives from the Walnuts Juglans regia L. are: catechin, gallocatechin, penta-O-acetyl-O-β-D-xylopyranosylellagic acid, gallic acid, methyl gallate, pedunculagin, casuarinin, hexaacetoxy-4-O-β-D-glucopyranosylnapthalene and 2,3-O-(S)-heptamethoxy-β-D-glucopyranosyldiphenoyl. Tetra-O-acetyl-9-β-D-glucopyranosylmegastigmen-3-one, tetraacetoxy-3-O-β-D- glucopyranosylsitosterol, glucose and sucrose were isolated as non-phenolics. Secondly, the study exploits methods to synthesize stilbene monomers and dimers isolated from Afrormosia elata. Afrormosia elata (Pericopsis elata) Harms, Fabaceae, is a tree native to the Guinean equatorial forests of West and Central Africa. The bark of this tree is used as a treatment for cancer by the local population. Stilbenes are a class of polyphenols with very 26 limited taxonomic distribution and varied biological activities which include, blood sugar reduction, antibacterial, antifungal, antioxidant, anti-HIV and anti-inflammatory. They posses COX-1 and COX-2 inhibitory effects, affect lipid peroxidation, LDL oxidation, function as phytoalexins, and have chemopreventative effects on cancer. The reported biological activities of stilbenes highlight the importance of stilbenoids as a resource for development of new drugs and pesticides. Since the occurrence of these stilbenoids in plants is in extremely low concentrations, we attempted synthesis of dimeric stilbenes with the aim of developing methods which may yield qualitative amounts. Syntheses of the monomeric stilbenes preceded that of the dimers. The classic Wittig reaction and the most recently developed metathesis reactions were the routes used to synthesize the monomers,while the route via the Heck coupling was considered for synthesis of the dimeric stilbenes.Item Open Access Comparison of injection moulded, natural fibre reinforced composites with PP and PLA as matrices(University of the Free State (Qwaqwa Campus), 2010-12-07) Mofokeng, Julia Puseletso; Luyt, A. S.Poly(lactic acid) (PLA) and polypropylene (PP) were comparatively investigated as matrices for injection moulded composites containing small (1-3 wt.%) amounts of short sisal fibre. The polymers and fibres were mechanically mixed, followed by extrusion at 190 C and injection moulding at the same temperature. The morphology, thermal and mechanical properties, and degradation characteristics were investigated using scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, polarised optical microscopy (POM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA) and tensile testing. From the POM photos it seems as if the fibres are equally well dispersed in the PLA and PP matrices. The SEM photos, however, show more intimate contact and better interaction between the fibres and PLA. This improved interaction was confirmed by the FTIR results that show the presence of hydrogen bonding interaction between PLA and the fibre. This improved interaction did not seem to have a significant influence on the yield stress, stress at break or tensile modulus of PLA. In the case of PP, however, the stress at break reduced observably, while the tensile modulus almost doubled in the presence of the fibre. The thermal stability (as determined through TGA) of both polymers increased with increasing fibre content, with a more significant improvement in the case of PP. The DSC results show a significant influence of the presence of the fibre on the crystallization behaviour of PLA, because both the melting temperature and melting enthalpy decreased with increasing fibre content, even at low fibre contents of 1-3%. This is the result of the strong interaction between PLA and the fibre, which immobilizes the PLA chains. The influence of the fibre on the melting characteristics of the PP was negligible. Both the storage and loss moduli of the PLA decreased with increasing fibre content below the glass transition of PLA, but the influence on the loss modulus was more significant. The DMA results clearly show cold crystallization of PLA around 110 C, and the presence of fibre gave rise to higher modulus values between the cold crystallization and melting of the PLA. The presence of fibre also had an influence on the dynamic mechanical properties of PP. The biodegradation of PLA and its composites was determined by keeping the samples in water at an elevated temperature for up to 10 days. The composites initially showed a larger mass loss than pure PLA, but after 10 days the pure PLA seemed to be more degraded. The SEM results of biodegraded samples show complete collapse of the surface of the PLA matrix after ten days.Item Open Access Computational, structural and electrochemical properties of metal (III) tris-betadiketonato complexes(University of the Free State, 2012) Freitag, Roxanne; Conradie, JEnglish: A series of MnIII(β-diketonato)3 complexes (β-diketonato = acac, ba, dbm, tfaa, tfth, tffu, tfba and hfac) were synthesized and characterized with the aid of mass spectroscopy, elemental analysis, X-ray diffraction (crystallography) and melting point measurements. The electrochemical study (cyclic voltammetry) showed that for MnIII(β-diketonato)3 complexes with more electron withdrawing R and R' groups on the β-diketonato ligands (RCOCHCOR')-, the redox potential of the [MnIII(β-diketonato)3] + e- [MnII(β-diketonato)3] redox reaction was found to shift to more positive potentials. The reduction potential of the the MnIII/MnII couple was correlated to electronic parameters (acid dissociation constant (pKa) of the uncoordinated b- diketones (RCOCH2COR'), the total group electronegativities [Σ(cR + cR')] and total Hammett sigma meta constant [Σ(σR + σR')] of the R and R' side groups of the b-diketonato ligands (RCOCHCOR') and the calculated electron affinity of Mn(β-diketonato)3 complexes. DFT computational studies were done on the Mn(acac)3 and Mn(dbm)3 complexeto understand the Jahn-Teller distortion that that MnIII(β-diketonato)3 complexes undergo. Electrochemical (cyclic voltammetry) studies were done on M(acac)3 complexes where M = V, Cr, Mn, Fe and Co. The reduction potential of the MIII/MII couple was correlated to electronic parameters such as the metal electronegativity (cPauling and cMulliken), calculated electron affinity and LUMO energy. DFT computational studies were done on the symmetry of V(acac)3 to investigate the Jahn-Teller distortion of the V(acac)3 complex. A DFT computational study was used to illustrate the d-orbital occupations of the M(acac)3 complexes ( M = V, Cr, Mn, Fe and Co).Item Open Access Contribution to preparation of polymer conjugates containing ferrocene derivatives(University of the Free State, 2000-11) Nokwequ, Mbulelo Geoffrey; Bariyanga, J.; Neuse, E. W.Cancer is one of the major killer-diseases in the whole world. It is a well known fact that the causes of cancer vary from person to person, they include, inter alia, exposure to carcinogenic substances like smoking, heredity, chronic irritation of body areas like exposure to radiation[l]. The alleviation of this disease is now one of the major challenges in the medical world. To this end, many drugs have been synthesized with the aim of curing this disease. The most widely used is cisplatin and its derivatives and it is more recently that metallocenes have also been employed as anticancer drugs. Recent studies have also shown that anchoring such drugs to biodegradable polymers improves their activity[2]. In this study ferrocene derivatives containing a BOC (tert-butoxycarbonyl) protected polyamine which is susceptible to platination were synthesized with a view of anchoring these to a suitable carrier polymer. Ethylenediamine, propylenediamine, and diethylenetriamine were first protected using BOC. These protected polyamines were characterized using NMR (¹ H nuclear magnetic resonance) spectroscopy, F AB-MS (fast atomic bombardment mass spectroscopy), FTIR (Fourier transform infrared) spectroscopy, and EA (elemental analysis). The protected polyamines were then attached to the ferrocenemonocarboxylic acid using a well known coupling agent DCC (N, N'- dicyclohexylcarbodiimide). These ferrocene derivatives were also analyzed using techniques such as NMR, MS, FTIR, and EA and they were found to have the expected structures. In parallel to this, a carrier polymer exhibiting a carboxylic acid side chain was synthesized from a poly (ethylene oxide) diamine and characterized by NMR, FTIR, GPC (gel permeation chromatography), ES-MS (electrospray mass spectroscopy), and EA . This polymer was later found to be water-soluble and has a long shelf life. This polymer was tested for biodegradability by digesting it with two endopeptidase enzymes, namely papain and proteinase A at 37 °C. Changes in molecular weight distribution of this polymer were then followed. The polymer was found to be slowly biodegradable.Item Open Access Copper based nanomaterials for oxidation catalysis(University of the Free State, 2009-11) Muller, Theunis Jacobus; Steyl, Gideon; Roodt, AndreasEnglish: The aim of this study was the synthesis simple O,O-bidentate ligand copper complexes of the type [Cu(Memal)2], [Cu(Etmal)2], [Cu(Trop)2] and [Cu(TropBr3)2], where Memal = 2- methyl-3-hydroxy-4-pyrone, Etmal = 2-ethyl-3-hydroxy-4-pyrone, Trop = Tropolonato and TropBr3 = tri-bromotropolonato and to do an evaluation of the oxidation catalysis of 3,5-ditert- butylcatechol to the 3,5-di-tert-butyl-1,2-benzoquinone and study the kinetics associated therewith. The ligands were selected to provide a systematic range of electronic and steric variation at the Cu(II) metal centre. Characterisation of the complexes was done by infrared spectroscopy (IR) and elemental analysis, as well as an X-ray crystallographic structure determination of selected compounds i.e., [Cu(TropBr3)2(DMSO)2] and 3,5-di-tert-butylcatechol. [Cu(TropBr3)2(DMSO)2] crystallised in the monoclinic space group C2/c with Z = 4 in the unit cell dimensions a = 18.002(7) Å, b = 20.351(7) Å, c = 7.578(3) Å, = 108.331(2) ° and the data were collected at -173 °C. Least-squares refinement led to a value of the conventional R1 index of 0.0320 and Rw = 0.0571 for 2873 reflections having I > 2 (I). The copper ion is coordinated by four oxygen atoms from two tri-bromotropolonato ligands. In addition there are two oxygen atoms from the two dimethylsulphoxide molecules coordinated to the copper centre in the axial positions, ensuring an overall octahedral geometry. The Cu-O(DMSO) bond lengths in the axial positions are significantly longer than the Cu-O bonds in the equatorial positions due to Jahn-Teller distortions. The 3,5-di-tert-butylcatechol crystallised in the triclinic space group P1 with Z = 4 in the unit cell dimensions a = 9.101(5) Å, b = 11.394(5) Å, c = 13.203(5) Å, = 83.653(5) °, = 79.601(5) °, = 85.091(5) °; and the data were collected at -173 °C. Leastsquares refinement led to a value of the conventional R1 index of 0.0124 and Rw = 0.3548 for 5675 reflections having I > 2 (I). The tert-butyl group on the 5 position of the phenyl ring crystallises in a 45:55 % statistically disordered position. A kinetic investigation was conducted to study the catalytic oxidation of 3,5-di-tertbutylcatechol to 3,5-di-tert-butyl-1,2-benzoquinone by the copper complexes listed above. The reaction was studied by two techniques namely, UV-Vis and GC in order to characterise the final product. All four complexes have the ability to oxidize 3,5-di-tert-butylcatechol, but there is a significant difference in the rate of oxidation between the complexes. [Cu(Memal)2] and [CuEtmal)2] have comparable rates and it is much faster than the rate of [Cu(Trop)2] and [Cu(TropBr3)2]. Different solvents also have an effect on the rate of the reaction: in acetonitrile the reaction only proceed to 14% completeness, but in methanol a 52% conversion is achieved in 24 hr under the same conditions. The rate of the reaction exhibits a limiting relationship with respect to molecular oxygen concentration. The catalytic mechanism that best describes the kinetics consists of five reversible steps. The first steps involves the coordination of 3,5-di-tert-butylcatechol to the copper followed by a second 3,5-di-tert-butylcatechol coordinating to the copper in the subsequent step. The third step involves the interaction with oxygen and the loss of one 3,5-di-tert-butylcatechol. A limiting value for the rate constant of the copper complex with molecular oxygen, k2 = 3.4(3) s-1 for [Cu(Memal)2] was determined. The fourth step is the rate determining formation of 3,5-di-tert-butyl-1,2 benzoquinone, defined by rate constants k3 and k-3, for [Cu(Memal)] is determined to be 3.7(6) x 10-5 M-1 s-1 and 2(5) x10-6 s-1. The fifth step completes the catalytic cycle and regenerates the starting complex i.e. the coordination of the Memal to the copper. The rates of the reaction seem to be both sterically and electronically dependent. TON and TOF values of 70.4 and 2.93 h-1 were observed for [Cu(Memal)2].Item Open Access A crystallographic and mechanistic investigation of manganese(i) tricarbonyl complexes(University of the Free State, 2013-11) Twala, Thembani; Visser, Hendrik G.; Schutte-Smith, MarietjieManganese has largely been used as a catalyst in epoxidation of olefins and the selective oxidation of unactivated C-H bonds in alkanes. Another major use of manganese is in water oxidizing catalysis, where manganese compounds are used in the production of hydrogen by water splitting. By looking at the manganese triad, a lot of radiopharmaceutical studies have been performed with Technetium. 99mTc is the radionuclide of choice since it has the ideal properties necessary for potential radiopharmaceuticals. Rhenium has been used as model for technetium radiopharmaceuticals and 188Re and 186Re have proved their use in bone metastases. Manganese has not been used in radiopharmaceuticals as it is somewhat toxic to the body. Some studies have been performed on tumor suppression using MnSOD, a mitochondrial enzyme. Very little work has been done on manganese coordination chemistry especially in terms of tricarbonyl aqua complexes. So far about 5 manganese tricarbonyl aqua complexes have been reported on the CSD. In this study, a comparison of manganese (I) and rhenium (I) tricarbonyl complexes is made. Rhenium (I) tricarbonyl aqua complexes have been synthesized by Kemp and Schutte et al. using N,N’-, N,O- and O,O’- bidentate ligands. The chosen N;N’- bidentate ligands are 2,2’-bipyridyl (Bipy) and 1,10-phenanthroline (Phen), N,Obidentate ligands are quinoline-2,4-dicarboxylic acid (2,4-Quin) and picolinic acid (Pico) and finally the O,O’-bidentate ligands chosen were 3-hydroxyflvone (Flav) and tropolone (Trop). In this study, the same N,N’- and N,O-bidentate ligand systems were used as well as 3-hydroxyflavone as O,O’-bidentate ligand in order to successfully compare these two metal cores. The synthesis of all the complexes has been reported in Chapter 3 and these were characterized by UV/vis, 13C NMR, 1H NMR and IR. Only two of the complexes were characterized by X-ray diffraction; fac-[Mn(CO)3(Bipy)(H2O)][CF3SO3] and fac- [Mn(CO)3(Phen)(H2O)][CF3SO3]. These monoclinic complexes both crystallized in the P21/c space group. The Mn-N,N’ bond distances were 2.051(2) Å and 2.058(19) Å for fac-[Mn(CO)3(Phen)(H2O)][CF3SO3], and 2.042(4) Å and 2.040(4) Å for the fac- [Mn(CO)3(Bipy)(H2O)][CF3SO3] crystal structure. A kinetic study was performed for the reaction between fac-[Mn(CO)3(Phen)(MeOH)]+, fac-[Mn(CO)3(Bipy)(MeOH)]+, fac-[Mn(CO)3(Pico)(MeOH)] and fac-[Mn(CO)3(2,4- Quin)(MeOH)] and different monodentate entering ligands pyridine (Py), thiourea (TU) and bromide ions (Br-). For all the reactions, the first order rate constants followed the following trend: k1 Br- > k1 TU > k1 Py. It was also observed that the N,O-bidentate complexes overall reacted faster than the N,N’-bidentate ligands. Both these trends were observed for the Re (I) complexes as well. Slightly negative ΔS† values, with large esd’s, were observed for all of the reactions which indicates towards an associative interchange mechanism. Overall, it was confirmed that the manganese complexes reacted much faster than the corresponding rhenium complexes. For the Phen and Bipy complexes, an increase in k1 of ~10 and ~7 for the reaction with bromide ions and ~40 and ~30 for the reaction with pyridine was found respectively. The Pico complexes showed an increase in k1 of a factor ~40 for the reaction with bromide ions and a factor ~590 for the reaction with pyridine. The complexes with the quinoline-2,4-dicarboxylic acid as bidentate ligand showed an tremendous increase of ~1150 for the reaction with pyridine from the rhenium complex to the manganese complex. This indicates the influence quinoline- 2,4-dicarboxylic acid has on the reactivity of the manganese (I) centre.Item Open Access A crystallographic and mechanistic study of Mn triad complexes as model radiopharmaceuticals(University of the Free State, 2015-02) Mokolokolo, Petrus Pennie; Visser, Hendrik; Brink, AliceA series of fac-manganese(I) tricarbonyl complexes were synthesized and analysed to better understand the chemical properties of the group 7 radiopharmaceutical model complex. Five new complexes containing N,O’, N,N’,O and O,O’ donating functionalities were successfully synthesized. The Schiff base ligands, SalH-mTol = 2-(m-tolyliminomethyl)phenol, SalH-cyHex = 2-(Cyclohexyliminomethyl)phenol and 5Me-SalH-Hist = 2-(2-imidazol-4-yl)ethyliminomethyl-5-methylphenol are derived from a salicylidene backbone. The O,O’ are the β-diketone ligands (acetylacetone= AcacH and trifluoroacetylacetone = TfacacH). The ligands were strategically selected to ensure systematic variation in electronic and steric effects. The synthesis of complexes fac-[Mn(Sal-mTol)(CO)3]2, fac-[Mn(Sal-CyHex)(CO)3]2, fac-[Mn(4-Me-Sal-Hist)(CO)2], fac-[Mn(Acac)(CO)3(OHCH3)] and fac-[Mn(Tfacac)(CO)3(OHCH3)] is reported and all the complexes were characterised by IR, NMR, UV-Vis and single crystal X-Ray diffraction to better understand the solid and solution state. All complexes afford an octahedral environment around the metal centre with the chelating ligands and three carbonyl ligands in facial arrangement. The octahedron is satisfied by a bridging oxygen atom in the dimeric complexes fac-[Mn(Sal-mTol)(CO)3]2 and fac-[Mn(Sal-CyHex)(CO)3]2, and a methanol molecule in complexes fac-[Mn(Acac)(CO)3(OHCH3)] and fac-[Mn(Tfacac)(CO)3(OHCH3)] Substitution kinetics of the coordinated methanol molecule in complexes fac-[Mn(Acac)(CO)3(OHCH3)] and fac-[Mn(Tfacac)(CO)3(OHCH3)] by a neutral imidazole ligand was evaluated. The negative values obtained for the activation entropy parameter, Δ𝑆��≠ [-88(1) J K-1 mol-1 and -18(6) J K-1 mol-1], in both complexes is suggestive of an associative type mechanism. As anticipated, the overall rate of methanol substitution in complex fac-[Mn(Acac)(CO)3](OHCH3)] is faster than in fac-[Mn(Tfacac)(CO)3(OHCH3)] as indicated by the overall larger k1 and K1, due to the presence of electron withdrawing fluorine atoms on the ligand backbone.Item Open Access Development and validation of bioanalytical assay methods for fentanyl in human plasma(University of the Free State, 2004) Abay, Efrem Teclehaymanot; Basson, S. S.; Hundt, H. K. L.; Purcell, W.Abstract not availableItem Open Access Development and validation of bioanalytical assay methods for sildenafil in human plasma(University of the Free State, 2004) Tesfu, Michael Kidane; Venter, J. A.; Hundt, H. K. L.; Basson, S. S.Abstract not availableItem Open Access Development of a viable protocol aimed at the synthesis of a selected natural product with possible application in the industry(University of the Free State, 2007) Jordaan, Lizette; Steenkamp, J. A.; Bezuidenhout, B. C. B.Since the introduction of synthetic analogues in both the health-related and cosmetic industry, a new generation has emerged in search of beneficial bioactivity compounds. This generation of “natural and green” focuses mainly on natural compounds and their health relating application. This research project focused on the natural polyphenolic compounds, Flavonoids. Flavonoids are known to be strong antioxidants, these are molecules that quenches reactive oxygen species (ROS). This generation of free radicals in the stratum corneum is the main factor in the development of skin damage and premature ageing. The two main sources of antioxidants are our body’s own in-house antioxidants or dietary antioxidants. Vitamins E and C were briefly discussed as antioxidants, but the main focus was the antioxidant activity of flavonoids. Through this study were unraveled the reaction pathways of natural antioxidants and their synthetic analogues, in chemical and biological systems. Emphasis was placed on their structure-activity relationship and correlated to their chemical and biological activities. Rooibos extract, known locally and overseas, was pursued not only for its bioactivity but rather its strong radical scavenging abilities. It is known that rooibos is not only unique to South Africa, but is hitherto the only natural source of the dihydrochalcone aspalathin (proven to be a very strong antioxidant). The uniqueness of this dihydrochalcone prompted the establishment of a viable synthetic route towards the construction of those crucial bonds in this target molecule, aspalathin. The first step would be the construction of the dihydrochalcone, 3,4,2’,4’,6’- pentahydroxy dihydrochalcone, which proved to be a challenging array of chemical reactivity. With acylations like Friedel-Craft and Fries, that is known to be very successful, it was decided to commence with the construction of the dihydrochalcone via an appropriate acylation step. Acylation of phenols can either occur via Cacylation (Friedel-Crafts reaction) or O-acylation (esterfication). This regioselectivity is governed by a set of principles incorporated in a theoretical premise, conveniently named as hard and soft acids and bases (HSAB). A new group of water tolerant Lewis acids, namely the lanthanide triflates have been introduced, and also the use of BF3·(C2H5)2O has proven success as catalyst in C-acylation. Simple phenolic substrates were used in the acylation process to assist the eventual establishment of a viable protocol. With these we were able to synthesize 1-hydroxy- 2-acetonaphthone and 3-(3,4-dihydroxy-phenyl)-1-(1-hydroxy-naphthalen-2-yl)- propan-1-one successfully, but in unsatisfactory yields (36 %). Despite many experiments under different conditions, starting with different model compounds, we were unable to improve the reaction yields. Within these reactions resorcinol produced the O-acylation product, 3’-O-hydroxy-phenyl 3-phenyl-propanoate and the C-acylation product, 2’,4’-dihydroxydihydrochalcone, whereas phloroglucinol only produced the O-acylated product, 3’,5’-dihydroxy-phenyl 3-phenyl-propanoate. From this analysis the conclusion can be made that, first occurring is the O-acylation followed by a Fries rearrangement in some cases. The neighboring hydroxy functionalities of phloroglucinol for example, posed a significant steric challenge for incoming electrophiles From the commencement of the project, replacement of the carboxylic acid group with the related, but with different chemical characteristics, nitrile groups was a necessary alternative. The Hoesch reaction was a good example of the HSAB principle, where in acid medium the nitrogen of the cyano group is protonated to afford the reactive electrophilic intermediate, the carbon of which is clearly a “softer” acidic site according to the HSAB theory. The C-acylated product, 2’,4’,6’- trihydroxy dihydrochalcone was produced in an impressive yield (73 %). During this reaction, an interesting result was also obtained, where the phenolic oxygen (“hard” base) as well as the aromatic ring (“soft” base) reacted with the nitrile to produce the product, 3’,5’-dihydroxy-4’-phenyl-propionic acid 1’-3-phenyl-propanoate. It is noteworthy to mention the fact that phloroglucinol was by far the most potent Cand O-nucleophile in a ‘normal’ series of model phenolic entries (phenol, resorcinol, catechol etc.) and resulted in the formation of the biphenyl, 3,5-dihydroxy-phenyl- 2’,4’,6’-trihydroxy-phenylether. Since the formation of a biphenyl ether is a rare occurrence, extensive methylation was employed to confirm the structure. Another part of this study includes the investigation and comparison of similar reactions under the influence of microwaves. Microwave reactions are known for their very short reaction times, higher product yields, less solvent utilized and more cost-effective energy consumption, but it was proved that selectivity was not increased. BF3·(C2H5)2O was the catalyst of choice for the selective C-acylation of phloroglucinol, rather than the water soluble Hf(OTf)4 Lewis acid. Different carboxylic acids were reacted with resorcinol and phloroglucinol with both Lewis acids as catalyst. In the one reaction between resorcinol and 3-phenylpropanoic acid with Hf(OTf)4 as catalyst, a reaction mixture was produced. The reaction mixture was acetylated to give both the O- and C-acetylated products, and from this result it was indicated that Hf(OTf)4 can act as both a Brønsted and Lewis acid in a catalytic cycle. The use of protecting groups was not only to optimize the yields obtained but also to understand BF3·(C2H5)2O and Hf(OTf)4 as catalysts. The low yields for the synthesis of the unprotected dihydrochalcones can be ascribed to: the formation of 3,5- dihydroxy-phenyl-2’,4’,6’-trihydroxy-phenylether, and the formation of 6,7- dimethoxy-indan-1-one and 5,6-dihydroxy-indan-1-one (intramolecular cyclization). At last the C-glycosylated flavonoid, aspalathin was synthesized. The best reaction result of phloroglucinol and 3,4-dihydroxyhydrocinnamic acid was catalyzed by BF3·(C2H5)2O to produce 3,4,2’,4’,6’-pentahydroxy dihydrochalcone, which resulted in a 20 % yield. A reliable method for the direct C-glycosylation of 3,4,2’,4’,6’- pentahydroxy dihydrochalcone with an unprotected sugar, D-glucose in aqueous media was used and yielded synthetic aspalathin (10.7%). Not only was this reported as the first 2 step synthesis of aspalathin, but was distinguished as the first complete free phenolic synthesis of a C-glycosylated flavonoid being reported. Combining this unique synthesis with a global industry such as cosmetics was possible. A study was conducted by Miao-Juei Huang and according to their results it was confirmed that aspalathin would be ideal for the use in topically applied cosmetic products, due to the accumulation of aspalathin in the stratum corneum. This causes a barrier on the skin with strong antioxidant properties, which protects the skin from harmful UV rays, reduce reactive oxygen species and slow down the aging process. Finally the potential of the desired compound to act as an active ingredient in commercial products was confirmed.Item Open Access Development of alternative technology for the production of meta-substituted phenolic compounds(University of the Free State, 2009-11) Sunil, Abraham C.; Bezuidenhoudt, B. C. B.English: Both m-cresol and resorcinol are important industrial starting materials in the production of many phenolic products. In a process similar to the one for the production of phenol, cresols are produced by reaction of toluene with propylene to give mixtures of o-, m- and p-isopropyltoluene. The corresponding cresols are subsequently obtained together with acetone via the hydroperoxides by air oxidation. Due to their close boiling points, m- and p-cresol are not separable by distillation and has to be obtained from these mixtures by elaborate adduct crystallisation, derivatization or chromatographic procedures, which results in pure synthetic m-cresol to be a very expensive commodity. Since it is known that mcresol can be produced selectively from o- or p-toluic acid, which is readily available from the corresponding xylene, by application of Keading’s Dow Phenol process, it was decided to investigate this methodology as an alternative for the synthesis of pure mcresol. In order to be in a position to optimise this process, it was decided to investigate the mechanism of the reaction through the use of X-ray diffractometry, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), infrared spectrometry (IR) and MALDI-TOF mass spectrometry. The starting point in the copper catalysed process for transforming o-toluic acid into mcresol, has been established by X-ray diffractometry to be the formation of tetrakis(μ2-2-methylbenzoato)bis(2-methylbenzoic acid)copper(II), with the typical paddlewheel structure of Cu(II) carboxylates, when o-toluic acid was reacted with basic copper(II)carbonate and magnesium oxide in refluxing toluene. Apart from the expected four o-toluic acid entities forming the paddlewheel structure, the crystal structure also indicated another toluic acid molecule to be attached to each copper atom through the carbonyl of the carboxylic acid moiety. Extension of the X-ray crystallographic investigation to the copper salts of p-toluic acid, m-toluic acid, p-ethylbenzoic acid, and 2,6-dimethylbenzoic acid indicted all of these compounds, except the copper (II) salt of p-toluic acid, to have structures similar to that of tetrakis(μ2-2-methylbenzoato)bis(2- methylbenzoic acid)copper(II). While the structure of tetrakis(μ2-4-methylbenzoato) bis(4-methylbenzoic acid)copper(II) basically also showed the paddlewheel configuration, the extra two toluic acid molecules attached to the copper atoms in the all of the other cases were absent in the structure of this compound. In this instance, interactions between an oxygen atom of one molecule and the copper of an adjacent molecule leading to an infinite “polymer” type chain along the a-axis of the crystal, was observed. Evidence gathered from DSC, TGA, and MALDI-TOF MS investigations of the transformation of tetrakis(μ2-2-methylbenzoato)bis(2-methylbenzoic acid)copper(II) into the product, suggested that this copper benzoate rearranges and cleaves into o-toluic acid and copper(I) 2-methyl-6-{[(2-methylphenyl)-carbonyl]oxy}benzoate at 164 °C. Decarboxylation of the latter at 249.5 °C gave o-toluic acid and 3-methylphenyl 2- methylbenzoate, which is hydrolysed into o-toluic acid and the desired product, m-cresol. In contrast to the copper salt of o-toluic acid, which showed clear temperature differences for the different steps in the reaction process, the salt of p-toluic acid displayed one continuous decomposition between 160 and 260 oC, thus rendering the identification of reaction intermediates at specific temperatures more or less impossible. In a process similar to that of cresols, resorcinol is commercially produced by selective formation of m-diisopropylbenzene followed by oxidative cleavage of the dihydroperoxide which is obtained through aerial oxidation of the diisopropylbenzene. While this process is used globally, it is hampered by large recycle streams arising from poor o/p selectivity during the alkylation of benzene as well as the limitation of low conversion (20%) in the oxidation step due to the explosivity of the hydroperoxide intermediate. Since it has been demonstrated that the Diels-Alder reaction could be applied to the synthesis of p-cresol from isoprene and vinyl acetate, application of this methodology to the synthesis of resorcinol, was subsequently investigated. Danishefsky’s diene (trans-1-methoxy-3-trimethylsilyloxy-1,3-butadiene), with the appropriate functional groups already trapped in the required enolic form, was selected as model substrate for the preliminary experiments with model dienophiles, methyl vinyl ketone and butyl acrylate and the novel cis- and trans-products, 4-acetyl-3- methoxycyclohexanone and butyl 2-methoxy-4-oxocyclo-hexanecarboxylate, obtained, albeit in low yields (7.49 and 6.59 % and 7.53 and 9.66 % respectively). When the reaction was extended to the more relevant methyl propiolate as dienophile, no direct Diels-Alder products could, however, be isolated and only methyl 4-hydroxybenzoate and methyl 4-{[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]oxy}benzoate were isolated from the reaction mixture in 5.51 and 5.74 % yields respectively. The formation of the phydroxybenzoate is explicable in terms of methanol elimination from the primary Diels- Alder product, while it is clear that the second product originates from conjugate addition of the formed hydroxybenzoate to methyl propiolate. While seemingly negative, the last Diels-Alder reaction, however, showed that the envisaged methodology could in principle be used for the preparation of resorcinol, but that care would have to be taken in order to avoid unwanted methanol release. If Chan’s diene [1,3-bis-(trimethylsilyloxy)-1- methoxy-1,3-butadiene] or an equivalent to it, could be used in a Diels-Alder reaction with an acrylate, the tendency towards methanol elimination might, however, be advantageous as it might lead to the mono-silylated resorcinol derivative in a single step. The viability of this Diels-Alder strategy towards the synthesis of resorcinol will form part of a future investigation. While negative from the point view of methodology for the synthesis of resorcinol, the Diels-Alder reaction between methyl propiolate and Danishefsky’s diene represents a new catalytic process for the preparation of methyl 4-hydroxybenzoate. This compound is widely used as a preservative in food, cosmetics and pharmaceuticals, while its free acid form (p-hydroxybenzoic acid), which is produced by Kolbe-Schmidt carboxylation of potassium phenolate with carbon dioxide, finds application in the liquid crystal industry.Item Open Access Development of methodology for the synthesis of 4-arylflavan-3-ol lactones(University of the Free State, 2008-05) Van Tonder, Bernadette; Bezuidenhoudt, B. C. B.; Steenkamp, J. A.; Kamara, B. I.English: The phenolic content of the heartwood of Peltophorum africanum (African wattle) and Burkea africanum (Red syringa) proved to contain a variety of compounds including the novel 4-arylflavan-3-ol lactones, 6-(3,4-dihydroxyphenyl)-6,6a,8,12b-tetrahydroisochromeno[ 3,4-c]chromene-3,8,10,11,12-pentaol and 6-(3,4,5-tri-hydroxylphenyl)- 6,6a,8,12b-tetrahydroisochromeno[3,4-c]chromene-3,8,10,11,12-pentaol respectively. Several attempts at the synthesis of these compounds to give final proof of the structure including the stereochemistry at the three chiral centres, failed due to the fact that the nucleophilicity of the pyrogallol ring of the gallic acid analogue (both protected and fee phenolic) is reduced to such an extent by the presence of the carbonyl group that it cannot effectively react with a C-4 electrophile generated on the flavan-3-ol starting material. In addition it became evident that the starting materials and products are sensitive to more drastic acid and basic reaction conditions to the extent that no desired products could be isolated from the attempted coupling of gallic acid analogues to C-4 functionalised flavan-3-ols. In order to alleviate these problems, it was envisaged to utilize a nucleophile without the carbonyl attached to it, thus changing the substrate to a pyrogallol entity containing a 1- hydroxypropyl - or allyl substituent. After coupling at C-4 of the flavan-3-ol the required carbonyl could then be introduced by consecutive water elimination and isomerization (1-hydroxylpropyl substituent) or isomerization (allyl substituent) followed by ozonolysis (with non-reductive work-up) and subsequent esterification. Since the starting materials for the synthetic strategy were not available commercially, both the flavan-3,4-diol and 1-(3’,4’,5’-trimethoxyphenyl)propan-1-ol had to be synthesized. While the phenylpropan-1-ol analogue was obtained in 64 % yield through utilisation of a Grignard reaction between 3,4,5-trimethoxybenzaldehyde and ethylmagnesium bromide, the required 3’,4’,7-trimethoxyflavan-3,4-diol became available through synthesis and subsequent manipulation of the appropriate chalcone. Thus trans-2’- ethoxymethoxy-3,4,4’-trimethoxychalcone, obtained by standard Claisen-Schmidt condensation of 2-ethoxymethoxy-4-methoxyacetophenone and 3,4- dimethoxybenzaldehyde, was epoxidized with dimethyldioxirane to give the chalcone epoxide in 98 % yield. Deprotection and cyclization to the dihydroflavonol were accomplished in 67.5 % overall yield via treatment of the chalcone epoxide with benzylmercaptan and tin(iv)chloride, followed by reaction of the subsequent -hydroxy- -benzylmercaptodihydrochalcone with silver tetrafluoroborate. Altough the syn- and anti-isomers of the mercaptodihydrochalcone were observed, both of these isomers led to only the 2,3-trans-dihydroflavonol. Finally, NaBH4 reduction of the dihydroflavonol gave the flavan-3,4-diol 70 % yield. Since the starting materials for - and products from the coupling reaction are known to be acid/base sensitive, it was decided to functionalise the flavan-3,4-diol through a mercaptan leaving unit that could be activated by thiophilic Lewis acid in order to induce coupling with the pyrogallol moiety. Silver tetrafluoroborate catalysed model reactions between 4-benzylmercaptochroman and the aromatic nucleophiles, resorcinol and methylated pyrogallol, gave the 4-arylchromans in 62 and 72% yield respectively. When the nucleophile was changed to 1-(3’,4’,5’-trimethoxyphenyl)propan-1-ol or the dehydrated version, 1-(3’,4’,5’-trimethoxy-phenyl)-1-propene, however, no couple could be detected. Since no apparent change in nucleophilicity could be identified as the cause of the reaction not giving any product, the failure can probably be ascribed to steric congestion brought about by the methoxy- and allyl - or propyl groups adjacent to the required point of reaction. As it is known from literature that radicals play an important role in the in vivo synthesis of many natural products, a biomimetic approach towards the synthesis of the 4- arylflavan-3-ol lactones was considered as next alternative. It was therefore envisaged that generation of a phenolic radical at C-2 of the pyrogallol ring of a flav-3-ene 3-gallate ester moiety could result in the formation of the desired lactone. Thus tetra-O-methyl catechin was converted into the 3-keto compound by mild IBX (2-iodoxybenzoic acid) oxidation in 61 % yield. Treatment of the catechin derivative with LDA followed by quenching of the enolate with t-butyldiphenylchlorosilane led to 3-tertbutyldiphneylsilyloxy- 3’,4’,5,7-tetramethoxyflav-3-ene in 84 % yield; thus proving that the double bond was indeed in the right position (between C-3 and C-4 and not C-2 and C-3) for the lactone to be formed. With the position of the double bond established, the enolization reaction was repeated with 2-bromobenzoyl chloride as model electrophile and the enol ester obtained in 22 % yield. In this instance, however, the desired enol ester was accompanied by the 2,3-unsaturated isomer (43 %). With all the uncertainties round the oxidation and enol formation sorted out, the final step in this strategy for the synthesis of the target lactones can now attempted with confidence. AIBN initiated radical cyclization of 3-O-(3”,4”,5”-trimethoxybenzoyl)-3’,4’,7-trimethoxyflav-3-ene and 3-O-(3”,4”,5”-trimethoxybenzoyl)-3’,4’,5’,7-tetramethoxyflav-3-ene will, however, receive attention in a subsequent PhD study.Item Open Access Development of new "green" methodology for the synthesis of substituted phenylacetic acid derivatives as precursors to isoflavonoids and related compounds(University of the Free State, 2013-01) Pieterse, Tanya; Bezuidenhout, B. C. B.; Marais, C.English: Flavonoids and isoflavonoids are known to exhibit many important physiological properties and are especially promising candidates for cancer chemoprevention. Similar to most natural products, studies directed at the synthesis of flavonoids have, therefore, emerged from the search for new compounds with beneficial biological properties. Metabolic studies related to flavonoids are, however, frequently hampered by the inaccessibility of a variety of optically active compounds. While a single method for the synthesis of enantiomerically enriched isoflavonoids has been published, this process utilizes phenylacetic acid derivatives which are not always readily available in all naturally occurring substitution patterns. Even though the synthesis of phenylacetic acids are possible via a number of routes, these are based on ancient low yielding chemical processes utilizing harsh reaction conditions, stoichiometric quantities of reagents and in many cases, poisonous heavy metals like lead and thallium. In order to address the availability of phenylacetic acid derivatives of variable substitution patterns, the current study was aimed at the development of methodology for the synthesis of phenylacetic acid derivatives that would be high yielding, environmentally benign, have a limited number of process steps, and are applicable to all naturally occurring flavonoid substitution patterns. In this regard it was envisaged that ozonolysis of substituted allylbenzenes would comply with all of the stated criteria and was therefore investigated as methodology for the synthesis of phenylacetic acid derivatives that could serve as building blocks during isoflavonoid preparations. Since substituted allylbenzenes of all oxygenation patterns are not available commercially, the allylic moiety was introduced into the required phenols by means of a allyl phenyl ether intermediate, through utilization of Williamson ether synthesis (allyl bromide; K2CO3, refluxing CH3CN) followed by Claisen rearrangement of the neat allyl phenyl ethers, allyl 3- methoxyphenyl ether and allyl 3,5-dimethoxyphenyl ether, under microwave irradiation (at 200 ºC in 15 min. intervals and 0-200 W variable power) to obtain the desired allylphenols, 1-allyl-2-hydroxy-4-methoxybenzene and 1-allyl-2-hydroxy-4,6-dimethoxy-benzene, in 44 and 88 % yield, respectively. Apart from the desired allylphenol, Claisen rearrangement of allyl 3-methoxyphenyl ether, however, also led to the formation of 1-allyl-2-hydroxy-6- methoxybenzene in 45% yield, indicating a lack of selectivity towards the formation of the sterically less hindered product under the prevailing reaction conditions. Since free phenolic substituents on the aromatic rings of the envisaged substrates might have a negative effect during ozonolysis reactions, the commercially available allylphenols as well as the two substrates prepared by allylation and Claisen rearrangement (vide supra) were subjected to methylation (MeI; K2CO3; refluxing acetone or acetonitrile) and the respective fully methylated analogues, 1-allyl-3,4-dimethoxybenzene, 1-allyl-2,4-dimethoxybenzene, 1-allyl- 2,4,6-trimethoxy-benzene, and 1-allyl-3,4,5-trimethoxybenzene, obtained in 79, 96, 80, and 77% yield, respectively. Ozonolysis [O3 (6-8 min.), DCM, 0 °C] with reductive work-up [N-methylmorpholine-Noxide (NMMO)] of 1-allyl-2-methoxybenzene, 1-allyl-4-methoxybenzene, and 1-allyl-3,4- dimethoxybenzene afforded the corresponding phenylacetaldehydes in 58, 88 and 15% yield, respectively. Ozonolysis of the highly oxygenated substrates, 1-allyl-2-hydroxy-4- methoxybenzene, 1-allyl-2,4,6-trimethoxybenzene, and 1-allyl-3,4,5-trimethoxybenzene, however, only led to cleavage of the aromatic ring and formation of unidentifiable product mixtures. Cleavage of the aromatic rings of these substrates was confirmed by 1H NMR analysis of the reaction mixture [O3 (6-8 min.), CDCl3, -78 °C] where the formation of the 1,2,4-trioxolane intermediate could be detected for the substrates that gave the desired phenylacetaldehydes but not for the highly oxygenated analogues. In order to reduce electron density on the aromatic ring of the highly oxygenated substrates and prevent ring ozonolysis in this way, the free hydroxy function on each substrate was changed into a trifluoromethanesulfonyl ester and the subtrates, 1-allyl-2- trifluoromethanesulfonyloxy-4-methoxybenzene, 1-allyl-4-trifluoromethanesulfonyloxy-3- methoxybenzene, 1-allyl-4-trifluoromethanesulfonyloxy-3,5-dimethoxybenzene, and 1-allyl- 2-trifluoromethanesulfonyloxy-4,6-dimethoxybenzene submitted to ozonation with NMMO work-up again. While the phloroglucinol based sulfonyl ester gave the desired phenylacetaldehyde in 71% yield, the other three substrates furnished NMMO induced double bond migration with the subsequent formation of the benzaldehyde equivalent products. When the ozonation reaction was repeated on the resorcinol, catechol and pyrogallol trifluoromethanesulphonyl esters, with replacement of the NMMO with dimethyl sulphide (DMS) as reductant, the desired phenylacetaldehydes or trioxolanes were, however, obtained in 63, 32 and 31% yield, respectively. Ozonolysis with oxidative work-up [(i) O3/MeOH; (ii) Ac2O-Et3N] applied to the monomethoxy substrates, 1-allyl-2-methoxybenzene and 1-allyl-4-methoxybenzene, afforded the desired methyl phenylacetates in 91 and 32% yield, respectively. Similar to what was found for the reductive work-up procedure, the higher oxygenated substrates had to be converted to their respective triflates before ozonolysis of the allylic double bond could be effected successfully and the phenylacetic acid esters, methyl 4-trifluoromethanesulfonyloxy- 3-methoxyphenyl acetate, methyl 4-trifluoromethanesulfonyloxy-3,5- dimethoxyphenyl acetate, and methyl 2-trifluoromethanesulfonyloxy-4,6-dimethoxyphenyl acetate obtained in 9, 17 and 65% yield, respectively. Since the published process for the stereoselective synthesis of isoflavonoids would require the phenyl acetates prepared through ozonolysis to be transformed into the corresponding amides, the possibility of direct formation of the nitrogen derivatives, like anilides, during the ozonolysis reaction was subsequently investigated. While first attempts at having the aniline present during the ozonolysis reaction only led to nitrogen oxidation, the process was amended to addition of the nitrogen nucleophile after formation of the 1,2,4-trioxolane, which resulted in the desired 2-methoxyphenylacetanilide being formed in 37% yield. The scope of this novel reaction was subsequently extended to the reaction of 1-allyl-4- methoxybenzene with acetamide leading to the product being obtained in 39% yield. While this reaction gave indications that deactivated nitrogen nucleophiles could also be used in this process, the reaction with 2-imidazolidinone, a secondary amide, did not succeed indicating that the new reaction still needs to be optimized to be useful in the enantioselective synthesis of isoflavonoids. Finally, it was shown during the current study that the phenylacetic acid derivatives prepared via ozonolysis could be transformed into deoxybenzoins, another isoflavonoid precursor, through formation of the acid chloride followed by reaction with a phenyl Grignard reagent. Thus phenylacetyl chloride could be reacted successfully with phenylmagnesiumbromide at - 78 oC in diethyl ether to give the deoxybenzoin in almost 60% yield.Item Open Access Die eerste oligomeriese neoflavonoiede: struktuur en sintese van modelverbindings(University of the Free State, 1993-05) Nel, Janetta Wilhelmina; Bezuidenhoudt, B. C. B.; Brandt, E. V.; Ferreira, D.Afrikaans: Hoewel oligomeriese flavonoïede reeds etlike dekades bekend is, is die eerste bi-isoflavonoïede eers onlangs uit Dalbergia spesies geïsoleer en is oligomere saamgestel uit neoflavonoïede nog onbekend. Ten einde die poel van oligomeriese isoflavonoïede uit te brei is die fitochemiese ondersoek na die fenoliese komponente in die kernhout van Dalbergia nitidula Welw. ex Bak, bekend vir die voorkoms van talle monomeriese iso- en neoflavonoïede, onderneem. Drie nuwe unieke iso-neoflavonoïed dimeriese verbindings bestaande uit 'n seldsame 3-fenielbenso[b]furaan- en vir die eerste keer 'n pterokarpaaneenheid, nl. (6aS,11aS)-2-, (6aS,11aS)-4- en (6aS,11aS)-8-[3-feniel-5-hidroksi-6-metoksibenso-[b]furan-2-ielmetiel]medikarpin, is inderdaad tydens die ondersoek gevind. Hierdie verbindings word in die eterekstrak vergesel deur 'n verdere dimeer waarin dieselfde neoflavonoïedeenheid aan (+ )-vestitol gebind is, nl. (3S)-8-[3-feniel-5-hidroksi-6-metoksi benso[b]furan-2-ielmetiel] vestitol. Benewens die dimere is 2', 7-dihidroksi-4'-metoksi-isoflav-3-een, die vyfde natuurlike isoflaveen, en (6aS,11aS)-2-hidroksi-3,9-dimetoksipterokarpaan as nuwe mono-mere verkry, terwyl 3,8-dihidroksi-9-metoksipterokarpaan vir die eerste keer as die 6aS,11aS isomeer geïsoleer is. Die bekende benso[b]furaan, centrolobofuraan, is ook saam met bekende verbindings soos (±)-ferreirien, di-O-metieldaidzein, (+ )-claussekinoon, 3-hidroksi-9-metoksikumestaan en (+ )-vestikarpin vir die eerste keer in hierdie spesie gevind, terwyl (+ )-medikarpin, (+ )-homopterokarpin, (+ )-vestitol, 3,9-dimetoksikumestaan asook (±)-liquiritigenien en isoliquiritigenien weereens verkry is. Aangesien onsekerheid omtrent die heterosikliese sisteem van die neoflavonoïedeenheid in die dimere bestaan het, is die sintese van 'n neoflavonoieddimeer met 'n seslid heterosikliese ring, (6 aS,11as)-4-[6-hidroksi-7 -metoksineoflav-3-een-3-iel] medikarpin d.m.v. 'n aldol-tipe kondensasie tussen 'n gesubstitueerde bensofenoon en pterokarpanielasetaldehied gevolg deur 'n sikliseringstap, aanvanklik aangepak (Skema). Weens die seldsame substitusiepatroon van die bensofenoon, is 2-hidroksi--4-metoksibensofenoon, as model, d.m.v. 'n Grignardreaksie tussen 4-metoksi-2-O-metoksimetielbensaldehied en fenielmagnesiumbromied daargestel en die pterokarpanielasetaldehied vanaf (+ )-medikarpin deur O-allilering (K2C03/ asetoon/ allielbromied) gevolg deur Claisenherrangskikking (N,N-dimetielanilien) en oksidatiewe splyting (OsO4/N-metielmorfolien-N-oksied gevolg deur NaIO4/MeOH) van die allielgroep, in 14% opbrengs verkry. Intermolekulêre aldolkondensasie (LDA/THF of asynsuur /H2S04) tussen die ptero-karpanielasetaldehied en die bensofenoon kon egter nie bewerkstellig word nie. Ten einde 'n Von Pechman-tipe kondensasie vir die sintese te kan benut moes die pterokarpanielasetaldehied na die ooreenstemmende suur geoksideer word, maar ten spyte van die aanwending van 'n verskeidenheid reagense (piridiniumdichromaat; RuCl3; Tollensreagens; KMn04; Ag20) kon 2-O-etoksimetiel-4,6-dimetoksifenielasetaldehied, as model, nie in noemenswaardige opbrengs na die ooreenstemmende suur geoksideer word nie. A.g.v. die onvermoë om die verlangde pterokarpanielasynsuur daar te stel, is die sintese van 'n model van die neoflavonoïedeenheid, 3-feniel-7-metoksineoflav-3-een, aangepak en is verestering van 2-hidroksi-4-metoksibensofenoon met fenielasetielchloried (K2C03/ asetoon) gevolg deur intramolekulêre siklisering (K2C03/ asetoon) en reduksie van die laktoonfunksionaliteit (B2H6THF) uitgevoer (10% opbrengs). Vergelyking van die chemiese verskuiwing van die CH2Sein in die 1H-KMR-(8 5.09) sowel as 13C-KMR-spektra (8 69.8) met dié van die natuurprodukte (8 4.13 - 4.24 en 8 21.0 onderskeidelik) het egter ondubbelsinnig getoon dat die natuurlike verbindings nie 'n seslid-heterosikliese ring in die neoflavonoïedeenheid bevat nie. Ten einde soortgelyke KMR-vergelyking vir die struktuur met die benso[b]furanielneoflavonoïed te doen, is voortgegaan met 'n modelsintese vir hierdie sisteem en is die verlangde 2-bensiel-3-fenielbenso[b]furaan d.m.v. Friedel-Grafts asilering van resorsinol met chloroasetielchloried, gevolg deur bensilering (bensielbromied, K2C03/asetoon) en Grignardreaksie van die gevormde bensofuranoon met fenielmagnesiumbromied daargestel. Hoewel presiese ooreenstemming in chemiese verskuiwing (8 4.17 en 8 32.8 onderskeidelik in die 1H- en 13C-KMR-spektra) van die metileengroep tussen die gesintetiseerde model en die natuurproduk nie verkry is nie, is dit aan verskille in struktuur en substitusiepatroon toegeskryf en kan 'n benso[b]furaanstruktuur aan die neoflavonoïedeenheid toegeken word.Item Open Access Direkte sintese van isoflavane en 2-bensieldihidrobensofurane via α-alkilering van fenielasynsuuresters(University of the Free State, 1991-05) Versteeg, Marietjie; Bezuidenhoudt, B. C. B.; Ferreira, D.Afrikaans: Hoewel verskeie isoflavonoïede wat fisiologiese aktiwiteit vertoon opties aktief geïsoleer is, bestaan daar tans geen metode vir die stereoselektiewe sintese van hierdie groep natuurprodukte nie. Aangesien geen direkte sintese vir isoflavane eweneens bekend is nie en hierdie groep die eenvoudigste chirale isoflavonoïede verteenwoordig, is die ontwikkeling van metodologie vir die enantioselektiewe sintese van isoflavane d.m.v. elektrofiele α-alkllering van fenielasetate uitgevoer. Ten einde die propanoïedskelet van isoflavane te lewer, word bensielelektrofiele met substitusiepatrone tiperend van isoflavonoïede tydens die alkileringsreaksie benodig en is 4-metoksibensielbromied (76%) m.b.v. reduktiewe halogenering (trimetielchlorosilaan) LiBr/tetrametieldisiloksaan direk van anysaldehied berei. Hierdie roete was egter onsuksesvol t.o. v. die sintese van 2-O-metoksimetiel- en 4-metoksi-2-O-metoksimetielbensielbromied, sodat lg. twee bensielbromiede na beskerming van die 2-hidroksigroep d.m.v. reduksie (NaBH4) en reaksie met metaansulfonielanhidried, LiBr en 2,6-lutidien vanaf salisiel- en 2-hidroksi-anysaldehied gesintetiseer moes word (75 en 70% opbrengs). AIkilering (litiumdiïsopropielamied/tetrahidrofuraan/ -78 - -15°C) van mentielasetaat,-propanoaat en -fenielasetaat, verkry deur reaksie van die ooreenstemmende suurchloried met (-)-mentol (60, 24 en 70%), met bensielbromied het mentiel-3-fenielpropanoaat, mentiel-3-feniel-2-metielpropanoaat en mentiel-2,3-difenielpropanoaat in 10, 16 en 50% opbrengs gelewer. Hoewel die opbrengs uit bg. reaksie onbevredigend laag was, is aangetoon dat stereoselektiwiteit m.b.v. 'n chirale alkohol wel verkry kan word en is die diastereomeriese propanoate in 'n verhouding 1.4 - 1.2 : 1 geïsoleer. Ten einde kondisies vir die alkileringsreaksies te optimiseer en dus die opbrengs te verhoog, is m.b.v. D20-blussing bepaal dat die esterenolaat na 15 min by -78°C reeds volledig gevorm is (m.b.v. litiumdiïsopropielamied of litiumisopropielsikloheksielamied) en dat die effektiwiteit van die proses deur die byvoeging van heksametielfosfortriamied verhoog kan word. Ten spyte van hierdie verbeterings was die opbrengs van die alkile-ring, waarskynlik weens basisgekataliseerde eliminasie van die suur, steeds laag en is alkilering met 'n reeks metielfenielasetate voortgesit. Reaksie van metielfenielasetaat, metiel-4-metoksifenielasetaat, metiel-2-metoksifenielasetaat, metiel-3,4-dimetoksifenielasetaat en metiel-2,4-dimetoksifenielasetaat met bensielbromied, 4-metoksibensielbromied, 2-O-metoksimetielbensielbromied en 4-metoksi-2-O-metoksimetielbensielbromied het die ooreenstemmende 2,3-diarielpropanoate in 20 - 86% opbrengste gelewer (Skema I). M.b.v. LiA1H4-reduksie (50 - 98%), gevolg deur verwydering van die metoksimetiel groep (3N HCI, MeOH) en suurgekataliseerde ringsluiting (p-tolueensulfoonsuur/benseen), is isoflavane vanaf die 2"- metoksimetielpropanoate berei (22 - 65% opbrengs). Weens die verhoogde migrasievermoe" het propanole met 'n 4'-metoksi of 3',4'- of 2',4'-dimetoksi B-ring egter tot 2-bensieldihidrobenso[b]furane (18 - 70%) aanleiding gegee en is die eerste direkte sintese ook vir hierdie seldsame groep verbindings daargestel.