Use of a fluorous bridge for diffusion controlled uptake of molecular chlorine in chlorine addition to alkenes

Article abstract of DOI:10.1039/b305629e

Fluorous solvent was used for passive transport of molecular chlorine from one side of the U-tube to the other, where addition of chlorine to alkenes was quantitative and diffusion controlled.

Full text of DOI:10.1039/b305629e

Use of a fluorous bridge for diffusion controlled uptake of molecular
chlorine in chlorine addition to alkenes†
Jernej Iskra,* Stojan Stavber and Marko Zupan
Laboratory of Organic and Bioorganic Chemistry, “Jozef Stefan” Institute and Faculty of Chemistry and
Chemical Technology, University of Ljubljana, Jamova 39, 1000 Ljubljana, Slovenia.
E-mail: jernej.iskra@ijs.si; Fax: ++386 1 4773 811; Tel: ++386 1 4773 631
Received (in Cambridge, UK) 19th May 2003, Accepted 12th August 2003
First published as an Advance Article on the web 20th August 2003
Fluorous solvent was used for passive transport of molecular
chlorine from one side of the U-tube to the other, where
addition of chlorine to alkenes was quantitative and
diffusion controlled.
fluorous phase that would serve for passive transport of gas to
the other side. Transport would be reaction driven and in this
way the bulk of the chlorine would be separated from the
reaction mixture.
The first condition for such a transport reaction is solubility
of the reagent in the middle phase. It is well known that organic
compounds are insoluble in fluorous solvents, as well as most
organic solvents and water. However, there are no data for
chlorine available. Therefore, we first tested the solubility of
chlorine in three different fluorous solvents: perfluoro-n-octane
(FC-77), perfluoro-n-hexane (FC-72) and perfluoro-2-(1-bu-
tyl)tetrahydrofuran (FC-75). We put 10 mL of solvent in a U-
tube; the reaction side was closed, while on the storage side
chlorine was introduced under slight pressure. The fluorous
phase became yellow, while its volume did not increase. The
amount of chlorine in solution was determined iodometrically to
be 0.066 mmol mL21 of FC-77, 0.055 mmol mL21 of FC-72
and 0.065 mmol mL21 of FC-75, respectively. Having
determined that chlorine is soluble in fluorous phases we
checked its solubility in a mixture of solvents. When dichloro-
methane was added to the yellow solution of chlorine in FC-77,
all the gas was immediately transferred to the organic phase,
leaving the fluorous phase colourless. The same happened with
hexane, methanol and acetonitrile as organic phases. Therefore
chlorine is soluble in a fluorous phase although it prefers an
organic phase.
Facile fluorous phase transfer of chlorine (gas/liquid, liquid/
liquid) serves as a good basis for further studies on the use of a
fluorous phase for passive transport of gas. In the first
experiment, a U-tube was charged with perfluorooctane (FC-
77), on the reaction side of the tube 1 mL of a 2 M solution of
cyclooctene in hexane was added and the tube closed. On the
storage side, a chlorine line was connected through a normal
glass joint. The pressure of chlorine was controlled by opening
of the line and by the level of the two phases. A slight pressure
of chlorine was applied and within a few minutes the fluorous
phase started to turn yellow. The fluorous phase was stirred at
the bottom with a magnetic stirbar in order to facilitate transport
of gas through the transport phase, while care had to be taken
not to mix the liquid phases. After 2 h reaction, the starting
compound was completely consumed and the organic phase
started to turn yellow. Chlorine gas was present in the reaction
mixture only after the end of the reaction, as could be seen from
its colour. The organic phase was then taken out, washed with
a diluted solution of NaHSO3, a saturated solution of NaHCO3
and dried. NMR analysis of the reaction mixture revealed that
only trans-1,2-dichlorocyclooctane was formed. After flash
chromatography on silica gel with hexane, dichlorocyclooctane
was isolated in 90% yield (Table 1).
The transport of molecules across a boundary is closely
connected to their concentration gradient. This is well exploited
in nature, while in chemistry membranes are mostly used for
this purpose. Sometimes a bulk solvent has been utilized as a
membrane and these experiments were usually performed in a
U-tube apparatus with a heavier organic phase at the bottom and
aqueous phases on both sides.1 Recently, Curran et al.
introduced fluorous triphasic reactions, where a fluorous
solvent was used as a liquid membrane for transfer of a purified
starting compound and for kinetic resolution of secondary
alcohols.2,3 In both cases, its use was connected with fluorous
synthesis, where one component of reaction is rendered
fluorous by incorporating a fluoroalkyl ponytail.4 Furthermore,
in “phase-vanishing reactions” a fluorous solvent was used for
passive transport of a heavier reagent in the lower phase through
the fluorous solvent to the upper organic phase and recently also
through a U-tube.5,6
Fluorous solvents have a low tendency to undergo van der
Waals interactions and because of that, they well solubilize a
range of gases.7,8 Furthermore, they are chemically inert and
non-flammable compounds.9 These properties led to their
application in reactions with gases,4a,10 where particularly
oxygen was used.8,11 Their use as a bulk membrane for passive
transport of a gas to a reaction mixture through a U-tube would
be of special interest. A particular advantage of such a system
would be its application for reactions with highly reactive and
corrosive gases and for exothermic reactions. This brought us to
the idea of using it as a transport phase for molecular chlorine,
so that this corrosive and very reactive gas would be eliminated
from the reaction mixture.
The design of the apparatus enables the use of one side of the
U-tube as a storage chamber (Scheme 1, storage phase) and the
other side as a reaction chamber. In between would be a
As the fluorous phase is immiscible with the majority of
organic solvents, we tested this chlorination method in various
solvents. As may be seen from Table 1, different non-polar and
polar organic solvents were successfully used and dichloro
product 2a was isolated in very good yields. A special case was
the nucleophilic solvent methanol, where besides 2a (58%)
different products were formed, that could not be isolated. On
the other hand, in a mixture of “light” fluorous solvents—
2,2,2-trifluoroethanol and benzotrifluoride—chlorination was
Scheme 1
† Electronic supplementary information (ESI) available: experimental. See
http://www.rsc.org/suppdata/cc/b3/b305629e/
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CHEM. COMMUN., 2003, 2496–2497
This journal is © The Royal Society of Chemistry 2003

not selective. For liquid alkenes there is no need to have a
solvent present in the reaction mixture. By this method,
chlorination could be solventless, yet the dichloro adduct is still
selectively formed.
The reactions were performed in chloroform as the phases
were better separated (Table 2). With all tested alkenes
chlorination was quantitative and only dichloro adducts were
detected and isolated by flash chromatography on silica gel.
Cyclooctene and cyclohexene gave trans-1,2-dichloro deriva-
tives. Styrene was also completely converted to the di-
chlorinated product, while traces of an eliminated compound
were detected after isolation on column chromatography.
Similar results were observed in reaction with b-methylstyrene
and 1,2-dihydronaphthalene. Chlorination also works well with
aliphatic olefins (trans-4-octene), as well as with terminal ones
(1-octene). Even a deactivated alkene like the ethyl ester of
cinnamic acid was quantitatively chlorinated.
In conclusion, fluorous transportive chlorination in a U-tube
could offer many advantages in direct chlorination reactions
with molecular chlorine, namely: the reaction phase is separated
from the bulk of the reagent, which is of special interest with
reactive, dangerous and highly corrosive compounds like
molecular chlorine; transport of chlorine through the fluorous
phase is slow and this slow uptake of reagent is very important
with reactive reagents and exothermic reactions; in terms of
“green” chemistry12 a solventless reaction phase is possible and
the fluorous solvent is completely recovered and reused.
Notes and references
Table 1 Chlorination of cyclooctene in a U-tube
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Yieldb
(%)
Solvent
timea/h
Hexane
CHCl3
CH3CN
DMF
TFE/BTF (2 : 1)
MeOH
none
2
2
2
1
3
2
2
90
91
89
84
50c
58d
88
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4
2
94 (1/1)d
5
6
7
8
1.5
1.5
1
93 (3 : 1)d
97
88
2
74 (1/1)d
a U-tube charged with 6 mL FC-77, a solution of 2 mmol of alkene in 1 mL
of CHCl3 was added and stirred gently at room temperature. b Isolated yield
after flash chromatography. c Product contained 15% of 1,2,2-trichloro-
1-phenylethane. d syn/anti ratio determined by NMR spectroscopy and
compared to literature values.
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