Thesis supervisor: József Rábai
Location of studies (in Hungarian): TTK Kémiai Intézet Abbreviation of location of studies: Kém.
Description of the research topic:
Based on well established fluorination methodologies, we shall develop effective synthetic procedures for the preparation of novel fluorinated alfa-amino acids; selected fluorinated model compounds and reagents that allows the study of self-disproportionation of enantiomeric mixtures (SDE), and some fluorination reagents, which makes easier the selective introduction of fluorines into target compounds.
The physicochemical properties of fluorine distinguish it from the other halogens, and led Pauling to describe it as a ‘superhalogen’. The fluorine atom is isosteric with hydroxyl and its van der Waals radius (1.47 Å) is close to that of hydrogen (1.20 Å), thus its substitution in organic compounds results in a sterically unchanged product. However, these substitutions have profound effects on the electronic properties of the compound, since fluorine’s electronegativity (4.0 on the Pauling scale) is the greatest of all elements, and the bond dissociation energy of C-F (110 kcal mol-1 in CH3F) is greater that of C-H (99 kcal mol-1). The introduction of (one to three) fluorine atoms into naturally occurring compounds, such as metabolic intermediates, have proved extremely useful tool in medicine and agriculture.
The purposeful introduction of long perfluoroalkyl-ponytails (e.g. Rfn = CnF2n+1, n=4,6,8,10) into catalyst precursor organic ligands, such as phosphanes (R3P), to make them perfluoroalkanes soluble, resulted in the invention of fluorous biphasic catalysis, which culminated in the evolution of fluorous chemistry. The reaction centre and the strong electron-withdrawing fluorous-ponytails should be separated by appropriate groups to maintain original reactivity, while their fluorous phase affinity can be tuned by the applied fluorous ponytails.
Fluorine containing compounds are becoming increasingly important in the medicinal, materials and agricultural fields. The ability of fluorinated molecules to modulate biological functions may not be surprising at the first glance, as fluorine ranks 13th on the most naturally abundant element lists. However, only a handful of naturally occurring fluoroorganic molecules has ever been reported. The vast majority of organofluorine compounds are manmade. Consequently, synthetic methodology to incorporate fluorine and fluorous synthons must be improved in order to prepare target fluoroorganic molecules on a practical scale. There is an incredible commercial driving force for improving fluorination reactions, as shown by forecasts for the world top selling drugs. Although several monoclonal antibodies and fused proteins are expected to appear among the top ten selling drugs by 2014, two fluorinated molecules (Crestor and Advair) will keep their leading positions.
Fluorine containing substituents (e.g. CF3, C(CF3)3, N(CF3)2, OCF3, SCF3, SF5, Rfn) play great role in pharmaceutical chemistry and materials science, whose introduction to molecules, chemical properties and reactivity have been compiled and discussed by Yagupolskii and Smart.
Further requirements: Szerves preparatív gyakorlati tapasztalat. Rutin 1H, 13C NMR és IR spektrumok értelmezése.
Number of students who can be accepted: 1
Deadline for application: 2014-11-27
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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