Please read the abstract in the section 00front of this document / Dissertation (MSc (Agric))--University of Pretoria, 2005. / Food Science / unrestricted

Addition reactions of pentafluorosulfur bromide (SF5Br) with fluoroolefins were studied. Three new adducts were prepared, SF5CHFCHC1Br, SF5CH2CH(CF3)Br, SF5CHFCFC1Br. SF5Br and CFC1=CHC1 yielded a small amount of product but attempts to add SF5Br to CF2=FCOF were unsuccessful. The mechanism for these addition reactions seems to involve a free radical addition pathway. Steric factors seem to be important in determining whether SF5Br will add to fluoroolefins. The new compounds, SF5CF(CF3)COF and SF5CF(CF3 )CONH2 have been produced from SF5CF=CF2. Analytical data, infrared, Raman, nmr and mass spectra are presented supporting the proposed structures for these new compounds.

Nucleophilic addition reactions of cyclohexylidenemalononitrile occur mainly in the conjugate manner.When the nucleophile was the hydride anion, selective reduction of the carbon-carbon double bond only took place at low temperatures. At ambient temperature, reduction was more estensive, resulting in ah eneaminonitrile. During the alkylation of cyclohexylidenemalononitrile, reduction by alkylmagnesium bromides was favored by the presence of a S-hydrogen on the alkyl group, and by the degree of branching in the latter; arylmagnesium bromides were however, less reactive. Alkaline hydrolysis of the Grignard adducts did not take place readily. The stepwise nature of this process was clearly demonstrated by the fact that, the substrates were hydrated to varying extents, depending on the steric environment of the cyano groups.Ball State UniversityMuncie, IN 47306

Digitized from microfiche to pdf format. / Thesis (PhD (Chemistry))--University of Stellenbosch, 1977. / Please refer to full text.

Ho Ho-On. / Thesis submitted in: August 2004. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references. / Abstracts in English and Chinese. / Thesis Committee --- p.i / Abstract --- p.ii / Acknowledgements --- p.iv / Table of Contents --- p.v / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- The Gaussian-3 Method --- p.1 / Chapter 1.2 --- The G3 Method with Reduced MΦller-Plesset Order and Basis Set --- p.2 / Chapter 1.3 --- Calculation of Thermodynamical Data --- p.2 / Chapter 1.4 --- Remark on the Location of Transition Structures --- p.3 / Chapter 1.5 --- Natural Bond Orbital (NBO) Analysis --- p.3 / Chapter 1.6 --- Scope of the Thesis --- p.4 / Chapter 1.7 --- References --- p.4 / Chapter Chapter 2 --- The Important Basic Concepts of Ab Initio Calculations and Their Application to Pericyclic Reactions --- p.6 / Chapter 2.1 --- Potential Energy Surfaces --- p.6 / Chapter 2.2 --- Ab Initio Method --- p.6 / Chapter 2.2.1 --- Basic Sets --- p.7 / Chapter 2.2.2 --- Correlation Methods --- p.8 / Chapter 2.3 --- Pericyclic Reaction --- p.10 / Chapter 2.4 --- The Perturbation Theory of Reactivity --- p.10 / Chapter 2.5 --- References --- p.11 / Chapter Chapter 3 --- Ab Initio Study of the Cycloaddition Reaction between Ethylene and Butadiene as well as That between Ethylene and Hexatriene --- p.13 / Chapter 3.1 --- Introduction --- p.13 / Chapter 3.2 --- Methods of Calculation --- p.15 / Chapter 3.3 --- Results and Discussion --- p.15 / Chapter 3.3.1 --- Reaction between ethylene and butadiene --- p.30 / Chapter 3.3.2 --- Reaction between ethylene and hexatriene --- p.34 / Chapter 3.3.3 --- Electrocyclic reaction of hexatriene --- p.37 / Chapter 3.4 --- Conclusion --- p.40 / Chapter 3.5 --- References --- p.41 / Chapter Chapter 4 --- A G3(MP2) Study on the Electrocyclic Reactions of [12]annulene --- p.43 / Chapter 4.1 --- Introduction --- p.43 / Chapter 4.2 --- Methods of Calculation --- p.44 / Chapter 4.3 --- Results and Discussion --- p.45 / Chapter 4.4 --- Summary --- p.51 / Chapter 4.5 --- Conclusion --- p.52 / Chapter 4.6 --- References --- p.52 / Chapter Chapter 5 --- A G3(MP2) Study on the Cycloaddition Reactions between Ethylene and Azines as well as Other Related Systems --- p.54 / Chapter 5.1 --- Introduction --- p.54 / Chapter 5.2 --- Methods of Calculation --- p.55 / Chapter 5.3 --- Results and Discussion --- p.55 / Chapter 5.3.1 --- Addition of ethylene to azines --- p.55 / Chapter 5.3.2 --- "Addition of ethylene to quinolene, isoquinolene and 1,8-naphthyridine" --- p.64 / Chapter 5.4 --- Conclusion --- p.70 / Chapter 5.5 --- References --- p.70 / Chapter Chapter 6 --- Conclusion --- p.72 / Appendix A Energetic and Bonding Investigation of Phosphabenzene and Arsabenzene: A Gaussian-3 Study --- p.73 / Chapter A.1 --- Introduction --- p.73 / Chapter A.2 --- Methods of Calculation --- p.73 / Chapter A.3 --- Results and Discussion --- p.74 / Chapter A.4 --- Conclusion --- p.77 / Chapter A.5 --- References --- p.77 / Appendix B Energetic and Bonding Study of Hexamethylenetetramine (HMT) and Fourteen Related Cage Molecules: A G3(MP2) Investigation --- p.79 / Chapter B.1 --- Introduction --- p.79 / Chapter B.2 --- Methods of Calculation --- p.80 / Chapter B.3 --- Results and Discussion --- p.80 / Chapter B.4 --- Conclusion --- p.87 / Chapter B.5 --- References --- p.87 / Appendix C The Gaussian-3 Theoretical Models --- p.89 / Chapter C.1 --- The G3 Theory --- p.89 / Chapter C.2 --- The G3(MP2) Theory --- p.90 / "Appendix D Calculation of Enthalpy at 298 K, H298" --- p.91

Lee Ho-Lam. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 71-72). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.iii / Table of Contents --- p.iv / List of Tables --- p.vi / List of Figures --- p.vii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- The Gaussian´ؤ3 Method --- p.1 / Chapter 1.2 --- "The G2++, a Modified Gaussian-2 Method" --- p.2 / Chapter 1.3 --- Density Functional Theory (DFT) --- p.2 / Chapter 1.4 --- Calculation of Thermodynamical Data --- p.3 / Chapter 1.5 --- Remark on the Location of Equilibrium and Transition Structures --- p.3 / Chapter 1.6 --- Natural Bond Orbital (NBO) Analysis --- p.3 / Chapter 1.7 --- Scope of the Thesis --- p.4 / Chapter 1.8 --- References --- p.4 / Chapter Chapter 2 --- Structures and Energetics of C3H6S+´Ø Isomers: A Gaussian-3 ab initio Study --- p.6 / Chapter 2.1 --- Introduction --- p.7 / Chapter 2.2 --- Methods of Calculation --- p.8 / Chapter 2.3 --- Results and Discussion --- p.8 / Chapter 2.4 --- Conclusion --- p.21 / Chapter 2.5 --- Publication Note --- p.21 / Chapter 2.6 --- References --- p.22 / Chapter Chapter 3 --- A Gaussian-3 Study of the C3H6S Isomers and the Dissociation Channels of Diradical ´ØCH2CH2SCH2´Ø and Its Radical Cation ´ØCH2CH2SCH2+ --- p.24 / Chapter 3.1 --- Introduction --- p.24 / Chapter 3.2 --- Methods of Calculation --- p.25 / Chapter 3.3 --- Results and Discussion --- p.26 / Chapter 3.3.1 --- Structures and Energetics of C3H6S Isomers --- p.26 / Chapter 3.3.2 --- Dissociation Channels of ´ØCH2CH2SCH2´Ø and ´ØCH2CH2SCH2+ --- p.34 / Chapter 3.4 --- Conclusion --- p.40 / Chapter 3.5 --- Publication Note --- p.41 / Chapter 3.6 --- References --- p.41 / Chapter Chapter 4 --- Computational Study on the Electrocyclic Reactions of [16]Annulene --- p.43 / Chapter 4.1 --- Introduction --- p.43 / Chapter 4.2 --- Methods of Calculation --- p.45 / Chapter 4.3 --- Results and Discussion --- p.45 / Chapter 4.3.1 --- Reaction (1) --- p.49 / Chapter 4.3.2 --- Reaction (2) --- p.50 / Chapter 4.3.3 --- Reaction (3) --- p.52 / Chapter 4.3.4 --- Overall Reaction --- p.53 / Chapter 4.4 --- Conclusion --- p.54 / Chapter 4.5 --- Publication Note --- p.55 / Chapter 4.6 --- References --- p.55 / Chapter Chapter 5 --- Computational Study on the Structures and Stabilities of Some Hypothetical Silicon Nanotubes --- p.57 / Chapter 5.1 --- Introduction --- p.57 / Chapter 5.2 --- Model Design and Methods of Calculation --- p.59 / Chapter 5.3 --- Results and Discussion --- p.59 / Chapter 5.3.1 --- "Armchair (n,n) SiNTs" --- p.60 / Chapter 5.3.2 --- "Zigzag (n,0) SiNTs" --- p.61 / Chapter 5.3.3 --- "Chiral (n,m) SiNTs" --- p.65 / Chapter 5.3.4 --- Stabilities of SiNTs at Elevated Temperature --- p.69 / Chapter 5.4 --- Conclusion --- p.70 / Chapter 5.5 --- References --- p.71 / Chapter Chapter 6 --- Conclusion --- p.73 / Appendix A --- p.74 / Appendix B --- p.76 / Appendix C --- p.77

The Streptomyces metabolite 2-crotonyloxymethyl-(4R,5R,6R)-4,5,6-trihydroxycyclohex-2-enone (COTC), the antheminones and the carvotacetone derivatives are all bioactive natural products, whose structure is based on the α oxymethyl-a,β-cyclohexenone moiety. Both COTC and antheminone A have been shown to exhibit cytotoxic and cancerostatic activity with low toxicity. The potent biological activity of these natural products has instigated numerous investigations into the synthesis of novel analogues in an attempt to determine the key structural features necessary for optimum bioactivity. The synthesis of a small library of novel anti-tumour agents which are structurally related to the natural products COTC and antheminone A is described, using the chiral pool material (-)-quinic acid as a starting material. At the outset, the aim of this project was to develop and optimise copper-mediated conjugate addition reactions and rhodium catalysed conjugate addition reactions of organoboron reagents to functionalised cyclic enones and subsequently, to apply the methodologies to the synthesis of the novel analogues. A range of novel mono-hydroxylated analogues bearing aryl side chains were prepared and their antiproliferative activity was assessed towards the A549 non-small cell cancer cell line. The biological assays revealed important structure-activity relationships and the most bioactive compound of this series had an IC50 value of 1.2 µM. In addition, the design and synthesis of a new class of GSH-activated prodrugs is described. These novel compounds are activated by GSH leading to intracellular release of an NQO1 inhibitor. The most potent compound of this new class of compounds had an IC50 value of 710 nm.

The oxidative addition of amino acids and other biologically interesting molecules to iridium{(I) complexes was studied and the reactivity of the resulting hydrido chelate complexes was investigated. Oxidative addition of amino acids to [Ir(COD)(PMe₃)₃]Cl resulted in the formation of meridional tris trimethylphosphine Ir(III) hydride complexes, with the amino acid chelated to the metal center forming 5 membered rings. The majority of the naturally occurring amino acids were studied as potential oxidative addition reactants. The amino acids with reactive side chains did not form clean products. The amino acids without reactive side chains did form clean products which were characterized by ¹H NMR, ³¹P NMR, ¹³C NMR spectroscopy, C,H analyses, and single crystal X-ray diffraction. The studies went on to investigate other 𝛂 amino acid compounds and attempts were made to form 6 membered ring complexes with 𝛃 amino acids. The reactivity of these complexes was also studied. A number of reaction conditions were used in attempts to induce the iridium amino acid complexes and various unsaturates, but the stability of the 5 membered ring system did not allow for insertion of unsaturates. An attempt was made to synthesize coordinately unsaturated complexes of iridium with amino acids. A variety of reactions were tried with the coordinately unsaturated compound, [Ir(COD)(DMPE)]Cl, but amino acid products were not produced in these reactions. Rather, an interesting rearrangement product of [Ir(COD)(DMPE)]Cl was formed and the crystal structure of [Ir (µ¹, µ³ - COD)DMPE]Cl complex was solved. Other attempts to induce reactivity of hydrido amino acid - Ir complexes involved synthesizing N-methyl amino acid complexes. The treatment of [Ir(COD)(PMe₃)₃]Cl with N-methylphenylalanine or N-methylglycine formed the respective chelate hydrido complexes. The reactivity studies of these complexes were negative. The insertion of an unsaturate was observed with 2-amino-4- pentenoic acid. This compound is an a-amino acid with a tethered olefin and when treated with Ir(COD)(PMe₃)₃]Cl binds through three sites (O, N, C) to the metal center. The Ir-C bond formed supports the fact that the olefin has inserted into the Ir-H bond. The crystal structure of this complex was solved. Several amino acid iridium complexes were tested for biological activity in NCI cancer and HIV assays. The complexes had no activity against cancer, but the phenylalanine complex did show moderate activity against HIV. The results prompted studies with other biologically interesting molecules and a number of sulfur containing compounds were studied. The formation of 4 membered ring systems was observed resulting from reactions of thiourea and analogs with [Ir(COD)(PMe₃)₃]Cl. These compounds are to be studied for their reactivity with unsaturates. / Ph. D.

The work focused on addressing four main objectives. The first objective was to quantify protein and amino acid substitution reactions. Michael addition reactions were used to modify the amino acids and protein. Amino acids alanine, cysteine, and lysine, and protein ovalbumin (OA) were substituted with different concentrations of ethyl vinyl sulfone (EVS). The substituted products were analyzed using Raman spectroscopy and UV-spectroscopy based ninhydrin assay. In case of alanine, Raman and UV results correlated with each other. With cysteine at lower EVS substitutions amine on the main chain was the preferred site while the substitution shifted to thiols at higher substitutions. This could only be discerned using Raman spectroscopy. Lysine has amines on the main chain and side chain while main chain amine was the most reactive site at lower concentrations of EVS while at higher concentrations side chain amines were also substituted. This information could be discerned using Raman spectroscopy only and not UV spectroscopy. In case of protein as observed by Raman and UV spectroscopy the reaction continued at higher concentrations of EVS indicating the participation of glutamine and asparagines at higher substitutions. However, the reaction considerably slowed down at higher EVS substitutions. The second objective of the study was to decrease the glass transition temperature (Tg) of OA through internal plasticization and also study the effects of the substituents on the thermal stability of OA. The hypothesis was by covalently attaching substituents to OA, number of hydrogen bonds can be reduced while increasing the free volume and this would reduce Tg. EVS, acrylic acid (AA), butadiene sulfone (BS) and maleimide (MA) were the four groups used. EVS was the most efficient plasticizer of all the four substituents. The Tg decreased with the increasing concentration of EVS until all of the reactive of groups on OA were used up. Tg decreased slightly with AA and BS while no change was observed with MA. However, the substituents showed exact opposite trend in thermal stability as measured using thermogravimetric analysis (TGA). The thermal stability of MA substituted OA was the highest and that of EVS substituted OA was least. FT-IR spectroscopy results indicated that all four substituents caused structural changes in OA. This implied that there were intermolecular interactions between substituted protein chains in case of AA, BS, and MA. This caused an increase in the thermal stability. EVS on the other hand is a linear chain monomer with a hydrophobic end group and hence could not participate in the intermolecular interactions and hence caused a decrease in Tg. As mentioned above the limitation to this technique is the number of available reactive groups on the protein. However, we successfully demonstrated the feasibility of this method in decreasing Tg of protein. The third objective was to create hydrogels by crosslinking OA with divinyl sulfone (DVS). Protein hydrogels due to their biocompatible nature find applications in drug delivery and tissue engineering. For tissue engineering applications the hydrogels need to be mechanically stable. In this study the protein was substituted with EVS or AA and then crosslinked with DVS. The swelling ratio was measured as a function of pH. All the hydrogels showed the same trend and swelled the least at pH 4.5 which is the isoelectric point of the protein. At basic pH conditions EVS substituted hydrogels swelled the most while AA substituted hydrogels showed least swelling. The static and dynamic moduli of the hydrogels were determined using tensile tester and rheometer respectively. The static modulus values were three times the dynamic modulus. The modulus of the control which is crosslinked OA was least and that of AA substituted OA was highest. The stress relaxation test also showed similar results in which AA substituted OA relaxed the most and the control relaxed the least. FT-IR of the dry hydrogels showed that the amount of hydrogen bonding increased with AA substitution. The hydrophilic AA end groups interacted with each other forming hydrogen bonds. These hydrogen bonds served as additional crosslinks there by increasing the modulus of the hydrogels. EVS on the other hand was incapable of interactions due to the lack of hydrophilic end groups. We were successfully able to create protein hydrogels and control the swelling and mechanical properties by varying the amount of substituted group. The final objective of the study was to create and characterize microstructures from substituted alanine and lysine. Alanine and lysine were substituted with different concentrations of EVS. Bars and fibers were observed for alanine at moderate substitutions while at higher concentrations random structures were observed using scanning electron microscopy (SEM). Lysine formed tubes at moderate EVS substitutions and rosettes at high concentrations of EVS as evidenced by SEM. FT-IR results suggested that instead of carbonyl one of sulfonyl bonded to the available amine in modified amino acids. And only in this case fibers, tubes and rosettes were observed. X-ray diffraction (XRD) results supported this observation. Using these results we hypothesized that the self assembled structures very much depended on the amount of EVS present in the substituted product and sulfonyl forming β-sheet analogs with amine. / Ph. D.

Nucleophilic additions are an important class of reactions in the preparation of several organic compounds. Metals facilitate nucleophilic additions in many cases. The present work Mechanistic Investigation of Metal Promoted Nucleophilic additions is an attempt to understand the mechanism of nucleophilic additions to imines and carbonyl compounds mediated by the transition metal complexes. Understanding the mechanism of metal promoted nucleophilic additions can facilitate the design and synthesis of more efficient catalysts. Chapter 1 provides a brief introduction to nucleophilic addition. A few named reactions that involve nucleophilic addition are described. An overview of the metal promoted nucleophilic addition reactions and their mechanisms are presented. A short note on the importance of understanding the mechanism of metal promoted nucleophilic addition is included. This section ends with the scope of the present work. Chapter 2 “Mechanistic Investigation of Titanium Mediated Reactions of Imines” deals with two reactions. The first reaction is the formation of reduced amines on reduction of imines. Amines and diamines are synthesized often from imines. A convenient route to such nitrogen containing compounds is through reduction of imines and through reductive coupling of imines respectively. Since both reactions occur in a parallel fashion, during the synthesis of diamines, amines are obtained as side products and vice versa. This problem is acute in the case of titanium based reducing agents. These reducing agents are called low valent titanium reagents because low valent titanium species are generated in situ either from titanium(IV) or titanium(III) reagents. There is no clear understanding of the nature of the low valent titanium involved in the reaction. To rectify this, a mechanistic understanding of this reaction is essential. An attempt was made to probe the mechanism of formation of amines using low valent titanium formed by using two different reducing agents namely phenylsilane and zinc. With the help of isotopic labelling studies, it was found that the mechanism of formation of an amine with phenylsilane involves a direct hydrogen transfer from phenylsilane to an imine. This was verified using deuterium labelled phenylsilane. With zinc, it follows a traditional titanacycle pathway which was verified by quenching with the deuterium oxide. A second reaction that has been probed is the alkylation of imines by Grignard reagents using chiral titanium complexes. Alkylation of imines is one of the suitable routes to prepare chiral amines. Alkylation of imines employing a Grignard reagent with Ti(OiPr)4 can proceed through two different pathways depending on the amount of the Grignard reagent used. Alkylation reaction with one equivalent of Grignard reagent can proceed through a Ti(IV) species and the alkylation reaction with two equivalents of the Grignard reagent can proceed through a Ti(II) species. The reaction proceeding through Ti(IV) is less wasteful as it only requires one equivalent of the Grignard reagent. The two pathways differ from each other in the nature of the transition state where the C-C bond is formed. To verify the favourable pathway, chiral titanium complexes were prepared and alkylation carried out. The alkylation results suggest that one equivalent of Grignard is sufficient to give good yields of the alkylated product and the reaction may proceed through a Ti(IV) promoted path. It was reported in the literature that at least three equivalents of Grignard reagent are required to get good yields of the alkylated product with zirconium complexes. This work suggests a greener alternate to alkylation of imines. Chapter 3 “Asymmetric Transfer Hydrogenation Reaction of Ketones in Water” deals with the synthesis of chiral ruthenium half-sandwich complexes employing a proline diamine ligand which has phenyl, ethyl, benzyl, or hydrogen as a substituent. These complexes were characterized by X-ray diffraction. In addition, all these complexes were obtained as single diastereoisomers. These complexes were used as catalysts for the reduction of a variety of ketones to chiral alcohols in water using sodium formate as a hydride source. Stoichiometric reaction between sodium formate and the catalysts showed the formation of hydride complexes as the active species. Based on the electronic effects observed, the key step is found to be a nucleophilic attack of hydride on the carbonyl carbon of ketones. In the transfer hydrogenation reaction with DCOONa, more of 1-phenylethanol- 1-2H1 was observed with all the ruthenium catalysts suggesting that the hydrogen from sodium formate is transformed into a metal hydride which is subsequently transferred to the ketones to form chiral alcohols. The catalysts were optimized with acetophenone as a model substrate. Only in the case of a catalyst which has a phenyl substituent, silver nitrate was found to enhance the formation of aqua complex which in turn resulted in good yields of the chiral alcohols. Among all the complexes studied, the catalyst bearing a phenyl group induces greatest enantioselectivity. It can also be recycled. Chapter 4 “On the Formation of a Ruthenium-PPh2H Complex Using 1- Phenylethane-1,2-diol” deals with the mechanism of formation of PPh2H from PPh2Cl. This unique transformation involves a ruthenium-cymene dimer, PPh2Cl and 1-phenylethane-1,2- diol. In the attempted synthesis of a ruthenium bisphosphinite complex, using the ruthenium-cymene dimer, chlorodiphenylphosphine and 1-phenylethane-1,2-diol, the formation of [Ru(η6-cymene)Cl2PPh2H] was observed in good yield. Formation of the expected ruthenium bisphosphinite complex was not observed. The reaction was carried out in the absence of 1-phenylethane-1,2-diol resulted in the formation of [Ru(η6- cymene)Cl2PPh2Cl] suggests that the diol acts as a reducing agent. To verify the source of hydrogen in the 1-phenylethane-1,2-diol, deuterated diols were prepared. The reactions with the deuterated diols revealed several interesting aspects of the formation of the Ru-PPh2H complex. Chapter 5 “Mechanistic Studies on the Diazo Transfer Reaction” deals with the synthesis of labelled azides and the labelled azidating reagent to probe the mechanism of the diazo transfer reaction. Azides are important precursors used for a variety of chemical transformations including the celebrated Cu(I) catalyzed click reaction. Azides are also used as protecting groups for amines as they can be conveniently reduced to amines. Azidation of amines usually yield azides, with retention of stereochemistry. There is a possibility that the azide formation can occur through the SNi mechanism with retention of configuration where nitrogen in the starting material will not be retained after forming an azide. The reaction was carried out with 13C and 15N labelled L-valine and L-isoleucine to probe this possibility. The resultant labelled azide has 15N retained in its position. This excluded the SNi pathway. To show where the nucleophilic amine group is attacking the azide, labelled imidazole-1¬sulfonyl azide was synthesized from NaN215N. Reactions were carried out with L-valine (labelled and unlabelled) in the presence of a metal catalyst and with unlabelled L-valine in the absence of catalyst. These results confirm the postulated pathways described in the literature.