Benaderings tot die sintese van stikstofringverbindings

M.Sc. (Chemistry)Please refer to full text to view abstrac

Approaches to the synthesis of selected nitrogenous heterocycles

Ph.D.The first part of the research described in this thesis involves the development of a new methodology for the synthesis of N-hydroxy pyrrolidines, starting from carbohydrates as building blocks. The products were identified as possible synthons for the stereocontrolled synthesis of isosteric analogues of polyhydroxylated indolizidine alkaloids. The consecutive reduction and cyclisation of selectively protected 5-0-mesyl hexose O-(tert-butyldiphenylsilyl) oximes to afford chiral N-hydroxy pyrrolidines is discussed. The mechanism involves a cascade of neighbouring group participation steps by the O-benzoyl protecting groups. This protocol gave rise to novel chiral N-hydroxy pyrrolidines in good overall yield. The choice of leaving group as well as a labile oxime protecting group proved to be of great import in the outcome of the cyclisation reactions. The second part of the research concerns the ongoing development in our laboratories of the synthesis of analogues of biologically active compounds. In this regard, we were interested in synthesising the aza analogues of f3-C-nucleosides and f3-C-glycosides. Our strategy involves the synthesis of a D-ribose derived chiral cyclic nitrone as the key synthon. A facile route towards cyclic nitrones was developed starting from suitably protected hemiacetals of Dribofuranose. Readily available tri-O-benzyl-D-ribofuranose was allowed to react with hydroxylamine hydrochloride to afford an acyclic oxime. Selective silylation followed by iodonation at C-5 (with inversion of configuration) furnished the cyclisation precursor. Anhydrous TBAF-mediated desilylation and subsequent intramolecular nucleophilic attack afforded a cyclic nitrone in excellent yield. Following the same protocol, 2,3-isopropylidene-5- 0-trityl-D-ribofuranose was converted into the corresponding nitrone. The 1,3-dipolar cycloaddition reaction of a nitrone to an alkene is an extremely powerful synthetic method for the creation of complex heterocyclic structures. The reaction of the Dribose derived nitrones with a,(3-unsaturated carbonyl compounds furnished the corresponding cycloadducts in good diastereomeric excess. The exo-product was isolated as the major isomer in each case. The reaction of a variety of carbon nucleophiles, including a Grignard reagent, with the nitrones led to the formation of interesting p-C-glycoside analogues. One of the carbohydrate nitrones was also converted into its thymine C-nucleoside analogue. This work clearly shows that the construction of chiral cyclic nitrones from D-ribose derivatives is an extremely efficient and simple procedure. The final part of the work described in this thesis involve the construction of CD-ring analogues of the natural metabolite, streptonigrin. The use of metalation and palladium catalysed cross-coupling reactions were investigated for the synthesis of highly functionalised biaryls. The synthesis and crystal structure determination of [3-(tert-butoxycarbonylamino)-4- pyridyl]-trimethyltin(IV) is discussed. The Stille cross-coupling reaction between an electron rich arylstannane and an electron poor aryl halide proved to be the most successful. The use of co-catalytic copper(I) had a dramatic effect on the overall yield and rate of this Stille crosscoupling reaction. This methodology would , in principle, allow the construction of the natural product and appropriate structural analogues

The Effect of CO Partial Pressure on Important Kinetic Parameters of Methanation Reaction on Co-Based FTS Catalyst Studied by SSITKA-MS and Operando DRIFTS-MS Techniques

A 20 wt% Co-0.05 wt% Pt/γ-Al2O3 catalyst was investigated to obtain a fundamental understanding of the effect of CO partial pressure (constant H2 partial pressure) on important kinetic parameters of the methanation reaction (x vol% CO/25 vol% H2, x = 3, 5 and 7) by performing advanced transient isotopic and operando diffuse reflectance infrared Fourier transform spectroscopy–mass spectrometry (DRIFTS-MS) experiments. Steady State Isotopic Transient Kinetic Analysis (SSITKA) experiments conducted at 1.2 bar, 230 °C after 5 h in CO/H2 revealed that the surface coverages, θCO and θCHx and the mean residence times, τCO, and τCHx (s) of the reversibly adsorbed CO-s and active CHx-s (Cα) intermediates leading to CH4, respectively, increased with increasing CO partial pressure. On the contrary, the apparent activity (keff, s−1) of CHx-s intermediates, turnover frequency (TOF, s−1) of methanation reaction, and the CH4-selectivity (SCH4, %) were found to decrease. Transient isothermal hydrogenation (TIH) following the SSITKA step-gas switch provided important information regarding the reactivity and concentration of active (Cα) and inactive -CxHy (Cβ) carbonaceous species formed after 5 h in the CO/H2 reaction. The latter Cβ species were readily hydrogenated at 230 °C in 50%H2/Ar. The surface coverage of Cβ was found to vary only slightly with increasing CO partial pressure. Temperature-programmed hydrogenation (TPH) following SSITKA and TIH revealed that other types of inactive carbonaceous species (Cγ) were formed during Fischer-Tropsch Synthesis (FTS) and hydrogenated at elevated temperatures (250–550 °C). The amount of Cγ was found to significantly increase with increasing CO partial pressure. All carbonaceous species hydrogenated during TIH and TPH revealed large differences in their kinetics of hydrogenation with respect to the CO partial pressure in the CO/H2 reaction mixture. Operando DRIFTS-MS transient isothermal hydrogenation of adsorbed CO-s formed after 2 h in 5 vol% CO/25 vol% H2/Ar at 200 °C coupled with kinetic modeling (H-assisted CO hydrogenation) provided information regarding the relative reactivity (keff) for CH4 formation of the two kinds of linear-type adsorbed CO-s on the cobalt surface