The home page of the Department of Physical and Organic Chemistry is located at http://www-k3.ijs.muzej.si/ijs-dept-k3.html

Laboratory for Organic and Bioorganic Chemistry

Staff:

• 2 senior researches (1 part time)
• 2 junior researcher
• 2 graduated student
• 3 undergraduated students

Equipment:

• spectroscopy: Varian EM 360L NMR, Perkin-Elmer 1310 IR, UV-VIS CECIL CE 6700, Series 6000
• separation techniques: GC: Varian 3700 and 3300 Models, Hewlett Packard 5890 Serie II; HPLC: LDC, Milton Roy, constaMetric three pumps, detectors: SpectroMonitor D-variable wave lenght, Fluorescence UV monitor fixed wave length; TLC and Column Chromatography
• other equipment: Ultra sound Vibra Cell SM, Photo reactors, Flash and Continuum-flow thermolyses Rotary-evaporators, Drying boxes, Balances, various shakers and reactors for fermentation
• High resolution mass spectrometer AutoSpec Q (Fisons, VG-Analytical), E B E q Q configuration
• Gass chromatograph HP 5890 (Hewlett Packard)

Scientific cooperation with:

• Department of Chemistry, University of Ljubljana
• European Network on the Synthesis and Molecular Recognition of Bioactive Fluorinated Molecules ( coordinator prof. J.P. Begue, CRNC Ura 1843 BioCIS, Chatenay- Malabry, France)
• University of Ljubljana
• National Institute of Chemistry, Ljubljana
• Public Health Institute of Slovenia, Ljubljana
• AlliedSignal inc., Buffalo Research Lab., Buffalo, NW 14210, USA

Selective fluorination of organic compounds has been a shared and important interest of organic chemists for the last three decades, and the impetus for the very intense research in this field of organic chemistry is the special physicocemical characteristic and the enhanced biological activity of fluorine- containing organic molecules. Such efforts have been focused mainly on development of new reagents and methods for selective introduction of a fluorine atom into organic molecule under mild reaction conditions as well as mechanistic study of these reactions.Reactions of phenyl-substituted alkenes with SelectfluorTM fluorinating reagent F-TEDA-BF4 in the presence of various alcohols resulted in the formation of vicinal fluoro- alkoxy adducts with Markovnikov type of regioselectivity. The stereochemistry of the fluoro-methoxylation addition reaction was found to be slightly syn predominant in the case of (Z)- stilbene, indene, and dibenzosuberenone, while equal amounts of both diastereoisomers were formed in the case of (E)-1-phenyl-1- propene and acenaphthylene. In the phenyl-substituted benzocyclene series the sterechemistry of fluoro-alkoxylation was found to be dependent on ring size and on the structure of the alcohol. Correlation of the logarithms of relative rates of fluoro-methoxylation reactions in a series of ten a-phenyl and a,a-diphenyl acyclic and cyclic alkenes with the ionization potentials of these alkenes resulted in a linear relationship with a slope of -2.75. Correlation of LOG krel for the present reaction with those for the reaction of the same alkenes with CsSO4F or XeF2 yielded excellent linearity for the pair F-TEDA / CsSO4F and scarcely good one for the pair F-TEDA / XeF2. Hammett correlation analysis of the reaction of substituted 1,1- diphenylethenes with F-TEDA in MeCN / MeOH solvent gave the reaction constant r+ of -1.42, so indicating a moderate electron deficiency on the reactive centre in the rate determining step of the reaction (B. Chem. Soc. Jpn. 1996, 69, 169). Direct conversion of a variety of cyclic and acyclic ketones regioselectively to a-fluoro ketones was achieved in high to excellent yield using 1-fluoro-4-hydroxy-1,4- diazoniabicyclo2,2,2octane bis(tetrafluoroborate) AccufluorTM - NFTh in acetonitrile solution (Tetrahedron Lett. 1996, 37, 3591).

Unsaturated cyclic a,a-difluoro ketones were prepared in high yield by the reaction of hydroxy-substituted aromatic derivatives with 1-fluoro-4-hydroxy-1,4- diazoniabicyclo2.2.2octane bis- (tetrafluoroborate) AccufluorTM - NFTh in methanol or acetonitrile solution, while a,a-difluoro phenones were obtained from phenylsubstituted alkynes in MeCN / H2O 9:1 reaction media (Synlet 1996, 693).

A comprehensive range of alkenes were converted, following Ritter- type reaction, to vicinal fluoroacetamides in high yield by reaction of 1-fluoro-4-hydroxy-1,4- diazoniabicyclo2.2.2octane bis(tetrafluoroborate) AccufluorTM NFTh in acetonitrile solution (J. Chem. Soc. Chem. Commun. 1996, 2247).

The same reagent was effectively used for selective fluorofunctionalisation of various polycyclic aromatic compounds. Naphthalene was almost site-selectively fluorinated to 1-fluoronaphthalene and phenanthrene to 9-fluorophenanthrene in over 80% yield in MeCN solution at 800C, while for transformation of pyrene to 1-fluoropyrene a lower reaction temperature ( 5oC ) was found to be necessary. In a series of substituted naphthalenes the regioselectivity as well as effectiveness of fluorination depended on the position and the nature of the substituents (Chem. Lett. 1996, 1077).

Dibenzofuran, diphenylether and biphenyl were used as target molecules in an investigation of the effect of N-F type of reagent ( F-TEDA, NFTh and FPD-B) and the reaction conditins on the fluorination process (Tetrahedron 1996, 52, 11341).

The transfrmations of various N-F reagents in water, acetonitrile, alcohols, and alkali hydrxides were investigated. First order kinetics for F-TEDA and NFTh transformations were established. F-TEDA is less stable in water than NFTh, while NFSi is very stable. The presnce of acetonitrile to an aqueous solution of F-TEDA enhanced the transformation, while a reaction in water/methanol solution was found tobe faster. The energy of activation for the transformation of F-TEDA in water, water/methanol and water/acetonitrile was determined (J. Fluorine Chem. 1996, 78, 137).