2
1
above its critical point of 36.4 °C and 72.5 bar. Depending
oxidation of PPh
as catalysts or promoters; the complexes were CoH(N
3
by N
2
O have involved metal complexes
)-
per mol catalyst, 62% isolated yield,
on the exact conditions, the density is high enough for the
2
scN
compounds, in the same manner as supercritical carbon
dioxide (scCO ). The reader should peruse the safety
warnings in the footnotes.22 In the past, the few low-
temperature oxidations with N O that have been reported
2
O to act as a solvent for many nonpolar organic
(PPh
-5 to 20 °C)
3
)
3
(6 mol OPPh
3
1
6,25
3-
and [MoO(CN)
5
]
3
(0.5 mol OPPh per
26
mol catalyst, room temperature, 48 h). Presumably the lack
of a requirement for a catalyst in the present system is due
to the higher temperature and the higher concentration of
2
2
were performed in either organic solvents or water. Using
the supercritical fluid as the solvent allows one to avoid the
use of a flammable liquid solvent and also to dissolve
substrates too hydrophobic to dissolve in water. A second
advantage is the facile separation of the product from the
N
2
O in the reaction phase.
Tests of the solubility of PPh
because of the rapid reaction. Instead, observations were
made of the solubility of PPh in scCO , a supercritical fluid
which is quite similar to scN O in all of its physical
properties. PPh (up to 65 mg) was completely dissolved in
the scCO at 150 bar and 65 or 100 °C. Literature measure-
ments of the solubility of PPh in scCO have only been
3
2
in scN O were not possible
3
2
2
solvent.23 The use of scN
2
O as both solvent and oxidant for
3
organic functional group transformations has not been
reported previously.
2
3
2
reported for 47 °C and below, but the mole fraction solubility
During tests of the effect of scN
we found that attempting to dissolve PPh
C and 100-140 bar resulted in its rapid oxidation to
phosphine oxide (Table 1 and eq 1). The N byproduct is
2
assumed but was not experimentally confirmed.
2
O on various compounds,
at 150 bar was found to be roughly temperature indepen-
3
in scN O at 100
2
27
dent. The mole fraction used in our experiments is an order
of magnitude lower than the solubility limit at this pressure.
It is unlikely that the oxygen source was anything other
°
24
than N
than 2 ppm of O
Two different batches of N
admission of air to the vessel could not have caused the
oxidation, because there is little reaction between PPh and
low concentrations of O under these conditions. A reaction
of PPh in scCO with no N O present gave 0% oxidation,
as did an experiment in scCO with 1 bar of added air. The
oxidation of PEt in a N O/CO mixture proceeded at a PEt
O mole ratio of 1:85, further evidence that the oxidation
could not have been caused by the presence of trace
2
O. The purity of the N
and less than 20 ppm of other impurities.
O were tested. Inadvertent
2
O was 99.998%, with less
2
PPh + N O f OPPh + N
2
(1)
3
2
3
2
The reaction can also be achieved at 65 °C, but it is
somewhat slower at this temperature. The pressure of the
3
2
N
2
O must be supercritical or it will be unable to dissolve
3
2
2
the phosphine. For example, the oxidation of PPh at 65 °C
3
2
3
:
proceeds readily at 100 to 140 bar but the starting material
was recovered entirely unreacted after an experiment at 10
3
2
2
N
2
bar. Note that PPh
diphenylphosphine, tricyclohexylphosphine, and triethylphos-
phine are oxidized more rapidly by scN O than is PPh
Triethylphosphine (470 µmol) was 43% oxidized after 90
min in a mixture of N O (6 bar, ca. 40 mmol) and CO (total
pressure 100 bar) at 50 °C. The same experiment but with
only CO and no N O gave 0% oxidation.
This oxidation of PR requires no added catalyst, although
3
at this temperature is a solid. Methyl-
(
21) Couch, E. J.; Kobe, K. A.; Hirth, L. J. J. Chem. Eng. Data 1961, 6,
29-237.
22) SAFETY WARNINGS: (a) Nitrous oxide is a thermodynamically
2
3
.
2
(
powerful oxidant. Never mix high concentrations of organic compounds
with scN2O. Explosions have occurred with a 9 vol % solution of ethanol
2
2
in scN2O and with a mixture of 1 g of ground coffee in 2.5 mL of
scN2O.3
1-33
To minimize the risk, we choose to keep the combustible
2
2
substrate to microscale quantities and Very low concentrations. For example,
the experiments with triphenylphosphine were typically performed at
0.00018 g substrate per mL of scN2O. In addition to using microscale
quantities of substrate, we employ a burst disk, blast shield, and eye
protection in all experiments. Diluting scN2O with scCO2 may further
enhance the safety. Combustible cosolvents should not be used with scN2O
3
catalysis by the vessel walls cannot be ruled out. In contrast
to the present results, previously reported examples of the
34
under any circumstances. (b) Triethylphosphine ignites on exposure to air
or pure N2O.
(
23) Jessop, P. G.; Leitner, W., Eds. Chemical Synthesis using Super-
critical Fluids; VCH/Wiley: Weinheim, 1999.
24) General Procedure for the Oxidation of a Phosphine by scN2O.
Table 1. Oxidation of Phosphines to Phosphine Oxides by
2
N O
(
A stir bar and 21 mg of PPh3 were placed in a 160 mL stainless steel vessel
while in a glovebox under argon. The vessel cap contains a burst disk, a
pressure transducer, a thermocouple, and a valve for N2O. The vessel was
closed, removed from the glovebox, heated to 100 °C, and then pressurized
with 140 bar of scN2O. The temperature was monitored by a thermocouple
inside a thermowell. After 3 h, the vessel was cooled to room temperature
and then placed in a bath of acetone/dry ice until the internal pressure
dropped to zero due to condensation of the N2O. At this point, the vent
valve was opened and the vessel slowly warmed to room temperature, the
N2O venting as it boiled. The vessel was then opened, and the product was
recovered from the bottom of the vessel by dissolution in CDCl3 and
substrate
T, °C
SCF
Ptotal, bar
time, h
% convn
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PMePh2
PMePh2
PCy3
65
65
65
100
100
100
64
65
70
50
50
N2O
N2O
N2O
N2O
N2O
CO2a
N2O
N2O
N2O
CO2b
CO2
10
100
140
130
140
100
140
140
140
100
100
2
2
2
0.5
3
0.5
2
4
4
1.5
1.5
0
43
34
66
100
0
71
100
100
43
0
1
31
1
analyzed by H and P{ H} NMR spectroscopy without further workup.
The product was pure OPPh3 (100% conversion, 94% isolated yield).
(
25) Pu, L. S.; Yamamoto, A.; Ikeda, S. Chem. Commun. 1969, 189-
PEt3
PEt3
9
0.
(26) Arzoumanian, H.; Nuel, D.; Sanchez, J. J. Mol. Catal. 1991, 65,
L9-L11.
(27) Schmitt, W. J.; Reid, R. C. Chem. Eng. Commun. 1988, 64, 155-
76.
a
bar of air added. b 6 bar of N2O added.
1
1
584
Org. Lett., Vol. 1, No. 4, 1999