Pyridine

La pyridine ou azine, de formule brute , est un composé hétérocyclique simple et fondamental qui se rapproche de la structure du benzène où un des groupes CH est remplacé par un atome d’azote. Elle existe sous la forme d’un liquide limpide, légèrement jaunâtre ayant une odeur désagréable et pénétrante (aigre, putride et évoquant le poisson). Elle est très utilisée en chimie de coordination comme ligand et en chimie organique comme réactif et solvant. Les dérivés de la pyridine sont très nombreux dans la pharmacie et dans l’agrochimie. La pyridine est utilisée comme précurseur dans la fabrication d’insecticides, d’herbicides, de médicaments, d’arômes alimentaires, de colorants, d’adhésifs, de peintures, d’explosifs et de désinfectants. Elle est un composé aromatique qui possède une réactivité différente du benzène. Historique La pyridine a été découverte en 1851 par le chimiste Thomas Anderson grâce à des études sur la distillation de l’huile d’os et de matières animales.

Iron Complexes for Hydrogen Activation and Catalytic Hydrogenation

Simona Mazza

Inspired by Nature several groups have developed structural and functional iron complexes mimicking the active site of the iron-hydrogenases, which show high reactivity in the H2 cleavage. Usually pendant bases have been incorporated onto families of Fe complexes in order to achieve active systems. In the view of these recent developments, in chapter two, we investigated the possibility of synthesizing novel iron (II) complexes bearing an amine internal base and providing an open site for substrate binding as catalysts for H2 activation. Pentacoordinated Fe(II) low spin complexes [(PhPNP)Fe(CO)(bdt)] (1), [(PhPNP)Fe-(CO)(Nbt)] (4), [(CyPNP)Fe(CO)(Nbt)] (5), [(dppe)Fe(CO)(Nbt)] (6) and the paramagnetic complex [(CyPNP)FeCl2] (10) have been synthesized and fully characterised. Unfortunately, when these complexes were tested as catalysts for hydrogenation reaction of a wide range of unsaturated substrates, no appreciable reactivity was observed. Same behaviour was observed in the case of complexes [(CyPNP)Fe(CO)(Cp)] (11) and [(CyPNP)Fe(CH3CN)(Cp)] (12) where the Cp ligand was installed in order to modulate the electronic and steric properties on the iron center. In chapter three, a new class of well-defined iron pincer complexes is reported. Several Fe(II) complexes supported by a 2,6-bis(phosphinito)pyridine ligand (PONOP) have been synthesized and fully characterised. In particular, the Fe-hydride complexes [(iPrPONOP)-Fe(CO)(H)Br] (14) and (iPrPONOP)Fe(CO)(H)(CH3CN) (15) could activate H2 at room temperature. Moreover, complexes 14 and 15 served as catalysts for the selective hydrogenation of aldehydes at room temperature. In presence of sodium formate as hydrogen donor, 14 and 15 showed an excellent reactivity in hydrogen transfer reaction of aldehydes. The mechanism of hydrogen activation and hydrogenation is discussed based on the observed reactivity of iron complexes. The feature of being chemoselective towards aldehydes and a broad functional-group tolerance make these iron-hydride systems remarkable in the class of the earth-abundant-metal hydrogenation catalysts. Chapter four is dedicated to the tuning of the Fe-PONOP systems reported in chapter three in order to synthesize similar iron(II) complexes exhibiting enhanced reactivity for H2 activation and hydrogenation of unsaturated substrates. As first attempt, complexes [(CyPONOP)Fe(CO)Br2] (22) and the analogous chloride [(CyPONOP)Fe(CO)Cl2] (23) bearing the stronger donor CyPONOP ligand were synthesized and tested as catalysts for hydrogenation reaction, but none of the substrates employed was reduced. As second attempt, the CO ligand was substituted with the better donor ligand tert-butyl isocyanide in presence of iPrPONOP as pincer ligand. Several Fe-PONOP complexes were synthesized and fully characterized. In particular the Fe-hydride complex [(iPrPONOP)Fe(tBuNC)(H)Br] (25) exhibited reactivity towards hydrogenation of aldehydes under the same reaction conditions reported for 14. No reaction was observed in presence of acetophenone, cyclohexene and 1-decene demonstrating that, although spectroscopically different, 25 did not exhibit enhanced reactivity relative to 14.

EPFL2015

Fluorine in an heteroaromatic context

Thierry Rausis

The organometallic approach to the functionalization of arenes and heteroarenes has recently been investigated by our group introducing modifications of the standard methods. This includes, in particular, the basicity-driven heavy halogen migration, which allows the introduction of a functional group at a not directly accessible position. Then, some attentions were reported toward nucleophilic aromatic substitution and especially to a regio-controlled attack at heteroarenes. Bulky trialkylsilyl groups were used to shield a given position by steric congestion against both electrophilic and nucleophilic attack. Using different electrophiles, commercially available 2,6-difluoropyridine was selected as substrate for a large proliferation of derivatives through organolithium intermediates. To allow for more regioflexibility, one can either rely on protective groups or introduce iodine which will be subsequently submitted to a basicity gradient-driven relocation and eventually a halogen/metal exchange. A systematic investigation was undertaken to explore the scope and the limitations of this latter option. Di-, tri- and tetrahalopyridines are used to explore the substituent effect in nucleophilic substitutions with the pyridine ring. An activating substituent as chlorine directed the nucleophilic substitution at the vicinal fluorine atom. Unprecedented was the finding that bulky 3-trialkylsilyl group effectively shielded the fluorine at the adjacent 2- and 4-positions, reorienting the nucleophilic substitution to the 6-position. To exploit the regioselectivity established by the "silyl trick", some halopyridines, such as 2,4,5-trifluoropyridine or 2,4-dichloro-6-hydrazinopyridine, were prepared for the fist time. Highly substituted derivatives isolated during nucleophilic substitutions were the starting point for the development of more complex structures such 2-amino-5-bromo-4-chloro-6-fluoro-3-nitropyridine obtained by using some of the developed techniques.

EPFL2005

Fluorine in an heteroaromatic context

Thierry Rausis

EPFL2005

Iron Complexes for Hydrogen Activation and Catalytic Hydrogenation

Simona Mazza

EPFL2015

The organometallic approach as a powerful tool for the site selective functionalization of halogenated pyridines

Iron Complexes for Hydrogen Activation and Catalytic Hydrogenation

Fluorine in an heteroaromatic context

Fluorine in an heteroaromatic context

The organometallic approach as a powerful tool for the site selective functionalization of halogenated pyridines

Iron Complexes for Hydrogen Activation and Catalytic Hydrogenation