Chemistry Reference
In-Depth Information
Chapter 22: Chemistry in Fluorous
Biphasic Systems
JÓZSEF RÁBAI, ZOLTÁN SZLÁVIK AND ISTVÁN T. HORVÁTH
1 Introduction
fluorotrialkyl amines [8,9] and supercritical carbon
dioxide [10].
One of the most vigorously studied areas of green
chemistry is the development of selective reagents
and catalysts with facile and complete separation
from the products [1]. Although solid reagents and
catalysts could provide easy separation from gaseous
and liquid products, the presence of various active
centres on the surface frequently leads to different
reactivity and thus low selectivity. Although the
selectivity of carefully designed soluble reagents and
catalysts could be extremely high because the active
centre(s) could be controlled at the molecular level,
the separation of the products could be a major limit-
ing factor for commercial developments. One of the
most promising approaches for the separation of
liquid products from soluble reagents and catalysts is
the application of liquid-liquid biphasic chemistry.
An effective biphasic system consists of a reagent or
a catalyst phase, containing a preferentially soluble
reagent or catalyst, and a second product phase that
should have limited solubility in the reagent or cata-
lyst phase (Fig. 22.1). The selection of the reagent or
the catalyst phase is governed by the solubility char-
acteristics of the product. For example, the Hilde-
brand solubility parameter scale (Fig. 22.2) could be
used to assess the solubility and miscibility of the
product with various solvents and to identify a well-
separable reagent or catalyst phase [2-5]. In general,
if the product is apolar then the reagent or the cat-
alyst phase should be polar, and if the product is
polar then the reagent or the catalyst phase should
be apolar. Reagents and catalysts can be made pre-
ferentially soluble in the reagent or the catalyst
phase by attaching solubilising groups to reagents or
catalysts in appropriate size and number. Although
reagents and catalysts soluble in water [6] and ionic
liquid [7] can be used for the synthesis and separa-
tion of products with lower polarity, the most apolar
media for biphasic systems are fluorous solvents such
as perfluoroalkanes, perfluorodialkyl ethers, per-
2 The Fluorous Biphase Concept
The fluorous biphase concept is based on the limited
miscibility of perfluoroalkanes, perfluorodialkyl
ethers and perfluorotrialkyl amines with common
organic solvents such as toluene, tetrahydrofuran
(THF) and acetone [8,9]. A fluorous biphasic reagent
or catalyst consists of a fluorous phase containing a
preferentially fluorous soluble reagent or catalyst
and a second product phase that may be any organic
or non-organic solvent with limited solubility in the
fluorous phase. Reagents and catalysts can be made
fluorous soluble by attaching fluorocarbon moieties
to ligands in the appropriate size and number. The
most effective fluorocarbon moieties are linear or
branched perfluoroalkyl chains with high carbon
number that may contain other heteroatoms (the
'fluorous ponytails'). Because of the electron-
withdrawing properties of the fluorine atom, the
attachment of fluorous ponytails could change sig-
nificantly the electronic properties and consequently
the reactivity of fluorous reagents and catalysts.
Therefore, the insertion of insulating groups before
the fluorous ponytail may be necessary to decrease
the electron-withdrawing effects [11-13].
Fluorous biphasic systems are well suited for con-
verting apolar reactants to products of higher polar-
ity, because the partition coefficients of the reactants
and products will be higher and lower, respectively,
in the fluorous phase. The net results are no or little
solubility limitation on the reactants and easy sepa-
ration of the products. Furthermore, as the conver-
sion level increases, the amount of polar products
increases, further enhancing product separation.
It should be emphasised that some fluorous bipha-
sic systems can become a single phase at increased
temperatures. Thus, a fluorous biphasic system could
combine the advantages of one phase reaction with
502
