Fluorous phase
The fluorous phase is a specialty of organic chemistry that deals with compounds in which hydrogen atoms are replaced by fluorine atoms and which therefore have special properties. The most characteristic feature here is that they do not mix with aqueous or organic phases with a low fluorine content.
introduction
With an increasing proportion of C – F bonds in the molecule, organic substances show an abnormal behavior in their physico-chemical properties. One speaks of perfluorinated substances when all C – H bonds have been replaced by C – F bonds. If a compound has a substantial proportion of C – F bonds, it is referred to as fluorous; if the compound has an insignificant proportion of C – F bonds, it is referred to as organic.
properties
Fluorine, especially perfluorinated compounds show clear anomalies in their physico-chemical properties. These include the following characteristics:
- Fluorous phase immiscible with aqueous and organic phases
- Very good solubility for gases
- Thermally adjustable miscibility
- extremely unreactive
- high density
- low surface tension
The following direct application examples result from this:
- Inert, hydrophobic storage medium
- Pump oil in vacuum technology
- Blood substitute
- Solvent water sensitive reactions
Physico-chemical basics
Unsubstituted alkanes have a flexible carbon structure with respect to rotations and are in the liquid state in an elongated form; the carbon structure has a zigzag structure. Compared to hydrogen, the fluorine atom has a ~ 23% larger van der Waals radius. Because of this, rotations along the CC bond axes of perfluorinated alkanes are sterically hindered. The rigid helical carbon structure means that the spatial arrangement in the liquid state leads to larger cavities in the medium. This explains the high gas solubility in perfluorinated substances, among other things. However, this is insufficient as an explanation for the miscibility, since miscibility gaps also occur in systems with a planar C framework. It is characteristic that, due to the high electronegativity of the fluorine substituents, perfluorinated substances without net polarity have atoms with negative partial charges on the molecule periphery, whose polarity can interact with direct neighbors. However, since fluorine is only a very weakly polarizable atom, intermolecular interactions due to induced dipoles are extremely small.
The behavior of perfluorinated compounds seems more understandable when compared with noble gases. Apart from the extremely low reactivity, the difference in boiling points between krypton , xenon and radon and the perfluorinated alkanes CF 4 , C 2 F 6 and C 4 F 10, which are similar in molar mass , is only between 25 and 30 K. This in turn suggests similar close intermolecular interactions.
The miscibility gaps are less due to attractive or repulsive interactions with fluorous substances, but rather to strong interactions between substances in other phases.
Methods in organic chemistry
The temperature-dependent miscibility can be exploited by using a two-phase system which becomes single-phase during the reaction by increasing the temperature. This simplifies the separation of the products and the recovery of catalysts. In order to avoid the use of persistent perfluorinated alkanes, reactions can be carried out in partially fluorinated hybrid solvents such as benzene trifluoride (BTF) in order to then carry out a separation by chromatography with fluorous column material.
Construction of fluorous reagents
In order to construct reagents for fluorous synthesis, the following structural elements are important:
- Ponytails: perfluorinated alkyl radicals
- Spacer: non-fluorinated phenyl rings or alkyl chains to shield the reactive center from the electron-withdrawing effect of the ponytails.
Reagents of fluorous synthesis
Fluorous catalysts are used, in particular costly transition metal catalysts which can easily be recovered by fluorous extraction.
In order to remove certain species from the reaction mixture, fluorous scavengers are used. Phase markings (tags) are used to mark a certain substance in the reaction mixture with a perfluoroalkyl radical, so that it remains in the fluorous phase even over several synthesis steps in the case of multi-phase extraction (phase labeling reagent).
The U-Tube setup is a combination of phase labeling and fluorous extraction, whereby two organic phases are separated by a fluorous one. The organic source phase contains a fluorine-labeled product with organic impurities. The labeled product dissolves in the fluorous phase and migrates to the target phase, which contains a reagent for demarking. At the phase boundary there is demarking, the marking remains in the fluorous phase, the product is demarked contained in the target phase.
Fluorous protecting groups are often used to protect functional groups and at the same time mark molecules for fluorous extraction.
Synthesis strategies
The yield of multicomponent reactions can be increased significantly by fluorous synthesis. In the Biginelli reaction, for example, an intermediate is formed from two of the reagents, which then reacts with the third starting material. The fluorous synthesis makes it possible to use an expensive or difficult to prepare starting material in deficit, the two other reactants, if possible, easy to prepare and inexpensive, but in large excess. The product can be obtained in high purity by fluorous extraction.
When planning the synthesis, the consistent use of three-phase extractions can increase the yield and improve the purity. In addition, expensive and toxic reagents can be recovered and processed in a targeted manner.
literature
- JA Gladysz, DP Curran, IT Horváth, Handbook of Fluorous Chemistry, 1st ed., Wiley-VCH, Weinheim, 2004
- P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, 2004
- A. Endres, G. Maas, Chem. Unserer Zeit 2000, 34, 382-393
- W. Zhang, Chemical Reviews , 2004, 104, 2531-2556
- A. Studer, S. Hadida, R. Ferritto, SY Kim, P. Jeger, P. Wipf, DP Curran, Science 1997, 275, 823-826
- DP Curran, Angew. Chem. 1998, 110, 1230-1255
- DP Curran, Angew. Chem., Int. Ed. 1998, 37, 1175
- RL Scott, J. Phys. Chem. 1958, 62, 136