.
Angewandte
Communications
Products derived from the capture of CO2 were not
detected in these reactions, which is in agreement with the
known inertness of carbon dioxide towards activation by
Lewis acids.[16] Oxygen was present in the reaction system in
all of the experiments reported in Table 1 and Schemes 2 and
3. Products characteristic of radical reactions, such as mono-
meric or dimeric alkanes or oxygenated products derived
from peroxydic intermediates,[5,14,17] were not detected in any
case. These results allow for disregarding the involvement of
radical intermediates in these reactions. Water, ethanol, or
organic solvents present in the supercritical medium strongly
inhibited the reaction rates[18] and led to the recovery of the
unchanged starting materials in all the cases. Control experi-
ments performed in a stainless steel autoclave by heating
solutions of ionogens 1 (0.03m) in n-hexane, diethyl ether,
carbon disulfide, acetonitrile, or dimethylformamide, led to
the recovery of the unreacted starting materials in all of the
cases, which permit us to rule out that the inner wall of the
stainless steel reactor might catalyze the reactions.
Solvent-promoted heterolysis of s-bonds initially forms
solvated contact ion pairs, which then dissociate by the
progressive penetration of the solvent molecules between the
ions to eventually reach the unpaired solvated-ion stage.[19,20]
To gain insight into the ion pair dynamics in scCO2, we
determined the stereochemical course of the reaction and the
secondary kinetic a-deuterium isotope effect. (R)-1-Chloro-1-
phenylethane ((+)-1aCl) with 70–80% ee completely race-
mized on standing in scCO2 at 608C and 250 bar for 5 h, and
gave racemic Friedel–Crafts adducts 3ao,p in the reaction with
1,3-dimethoxybenzene (2) in scCO2 under the same condi-
tions. Control experiments showed that Friedel–Crafts
adducts 3a do not undergo 1-phenylethyl group transfer
reactions in scCO2 at 608C for 5 h in the presence of hydrogen
chloride (2 equiv) and 1,4-dimethoxybenzene (4 equiv). This
result allowed us to rule out that Friedel–Crafts adducts 3a
undergo acid catalyzed racemization under these reaction
conditions. A secondary kinetic a-deuterium isotope effect
was determined from the competitive reactions of equimolar
amounts of 1aCl and [1-D]-1-chloro-1-phenylethane ([D]-
1aCl, 98 atom% D) with 2 (4 equiv) in scCO2 at 408C and
250 bar for 1 h to achieve alkyl halide conversions of about
20%. An averaged kH/kD value of 1.168 Æ 0.014 was obtained
for both isomeric Friedel–Crafts adducts 3a from 5 inde-
pendent runs.
departure of the leaving group. These results are in agreement
with the reactivity exhibited by 1-bromoadamantane (1dBr)
in scCO2 (Table 1, Scheme 2a,c). Remarkably, the kH/kD value
reported for the solvolysis of 1aCl in 97% aqueous 2,2,2-
trifluoroethanol at 258C was 1.158.[11c]
The ability of scCO2 to ionize polar carbon–halogen bonds
and to dissociate the resulting ion pairs can be related to the
well-established clustering effect of scCO2 around polar
solute molecules.[4,5,22] The spectroscopic and theoretical
studies reported[23] for the ion-quadrupole complexes of
halide anions with carbon dioxide in the gas phase have
evidenced the transference of charge density from the
halogen to the oxygen atoms with concomitant distortion of
the CO2 molecule from linearity. Solvent clustering around
the polarized carbon dioxide molecules coordinated to the
leaving group would further disperse the negative charge
density and contribute to dissociate the ion pair. In this way,
carbon dioxide would play the role of an H-bonding solvent
by efficiently accepting electron density from leaving
groups.[24] The negative charge densities localized at the
oxygen atoms of the carbon dioxide molecule might stabilize
the increasingly electron-deficient carbon atom of the ion-
ogen. Nevertheless, these interactions fail to activate carbon
dioxide to react with the highly activated nucleophiles present
in the reaction medium.
In summary, we have found that scCO2 ionizes polar
carbon–halogen bonds, dissociates the resulting ion pairs, and
escapes from the capture by the carbocation intermediates at
temperatures above 408C. This behavior allows carbocation
reactions to be observed in scCO2 in the absence of any acidic
or protic additive. The ionizing and dissociating abilities
exhibited by scCO2 in these reactions are unprecedented for
a reaction medium with a lower dielectric constant than
pentane and non-hydrogen-bonding behavior. This informa-
tion is valuable for designing efficient and competitive
chemical processes in scCO2 and also for a better under-
standing of the reactivity of carbon dioxide.
Received: May 3, 2013
Revised: August 2, 2013
Published online: October 15, 2013
Keywords: carbon dioxide · solvent effects · solvolysis ·
.
supercritical fluids · sustainable chemistry
Racemization of (+)-1aCl in scCO2 indicates that the
reaction medium dissociates the contact ion pair enough to
allow carbocation rotation prior to collapse with the chloride
anion. By way of comparison, the solvolysis of the optically
active (+)-1aCl in absolute ethanol at 708C has been
reported to proceed with about 5–15% net inversion.[11] The
kinetic a-deuterium isotope effect, kH/kD = 1.168, found for
the reaction of 1aCl with 2 in scCO2, suggests that the rate-
determining step of the reaction is the dissociation of the ion
pair.[21] Accordingly, the electrophilic species involved in this
Friedel–Crafts reaction would be unpaired carbocations.
Values of about 1.15 for the kinetic a-deuterium isotope
effects in the solvolysis of organic chlorides have been
considered indicative of limiting SN1 reactions[11,21] in which
the solvent does not provide nucleophilic assistance to the
[1] a) Handbook of Green Chemistry, Vol. 4 Supercritical Solvents
(Eds.: W. Leitner, P. G. Jessop), Wiley-VCH, New York, 2010;
b) Green Chemistry Using Liquid and Supercritical Carbon
Dioxide (Eds.: J. M. DeSimone, W. Tumas), Oxford University
Humayun, M. T. Schulberg, A. Sengupta, J. N. Sun, J. J. Watkins,
Caballero, E. Despagnet-Ayoub, M. M. Dꢁaz-Requejo, A. Dꢁaz-
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 13298 –13301