Experimental Section
General Procedure. All reagents are obtained com-
mercially and used without further purification. H NMR
reaction mixture is heated under reflux, and 0.3 kg of 1,2-
dibromoethane is then added to the reactor. 2-Bromotoluene
(19.03 kg) and THF (51.6 kg) are slowly and simultaneously
added over an hour. The Grignard formation is followed by
GC, the reaction is complete after an hour of stirring.
The second crop of magnesium (3.2 kg) is added to the
reactor. The o-bromochlorobenzene (23.3) and THF (50.2
kg) are then simultaneously introduced dropwise over an
hour. Stirring is maintained an hour under THF reflux until
the formation of the diarylGrignard reaches completion
(reaction followed by GC).
The mixture is cooled to room temperature. Copper
chloride (1.1 kg) is added. The dicyclohexylphosphine
chloride (29.6 kg) is added dropwise over an hour, and the
reaction mixture is stirred overnight at room temperature.
The mixture is quenched with 71 kg of aqueous sodium
bisulfite and 72 L of water. Thirty-eight kilograms of ethyl
acetate is added. The layers are separated. THF is distilled
from the organic layer, and the phosphine is allowed to
crystallise in ethyl acetate at 0 °C for an hour. The solid is
filtered and rinsed with 2 × 13 kg of ethyl acetate. The
phosphine is afforded as white crystals.
1
spectra are determined on a 200 MHz spectrometer. Melting
points are determined on a Buchi B-545 capillary melting
point apparatus and are uncorrected. Each compound pre-
pared herein is characterized by GC, GC-MS and 1H NMR
spectroscopy. All reported yields are based on the weight of
the isolated product.
Gas Chromatography. Gas chromatography is carried
out using a Varian CP-3800 gas chromatograph equipped
with a FID detector and a fused silica capillary column DB-
17 (30 m × 0.32 mm × 0.25 µm). All samples are examined
under the following temperature gradient: temp 1, 100 °C
(0 min); temp 2, 300 °C (5 min); rate 30 °C/min, total run
time 11.67 min. Conversions are determined by direct
integration of the peak areas of the gas chromatograph rather
than by constructing calibration curves using standard
solutions of each component. GC-MS data are acquired
using a HP 5890 series II gas chromatograph using the same
temperature gradient as described for GC analysis.
N-p-Toyl Benzophenone Hydrazone. In a 16-L glass
reactor, equipped with a condenser and a mechanical stirrer
and linked by an optic fiber to a Raman spectrometer, are
charged, under nitrogen atmosphere, 4-chlorotoluene (1.605
kg, 12.675 mol) and ground sodium hydroxide (709.8 g,
17.745 mol) in 8 L of freshly degassed tert-amyl alcohol.
The mixture is heated at reflux. The complex catalyst is
preformed under argon by mixing Pd(OAc)2 (1.42 g, 6.3
mmol) and MePhos (4.61 g, 12.7 mmol) for 20 min at room
temperature and then adding into the glass vessel. Benzophe-
none hydrazone (2.487 kg, 12.675 mol) is added by 13
portions every 10 min. Reaction is followed by Raman
spectroscopy. When the reaction has reached completion, the
reaction mixture is cooled to room temperature, and the
insoluble salts are quenched with water (2 L). The layers
are separated, and the arylhydrazone is crystallized at about
5 °C in the organic phase. The solid is filtered, washed with
2.5 L of tert-amyl alcohol, and dried at 40 °C (10 mbar).
The arylhydrazone is afforded as a pale yellow solid (93%).
1H and 13C NMR spectra are in accordance with the literature
data.1b
N-p-Tolylhydrazine Salt. In a 16-L Buchi glass reactor
equipped with a condenser and a mechanical stirrer is placed,
under argon, N-p-tolyl benzophenone hydrazone (2.477 kg,
8.65 mol) in 9.9 L of hydrochloric acid (aqueous solution at
37% w). Ethanol (990 mL) is then added. The reaction is
allowed to stirr for 24 h at room temperature. Conversion is
followed by GC analysis. On conversion, the solid formed
is filtered, washed three times with 4 L of dichloromethane,
and dried at 40 °C (10 mbar). The hydrazine salt is afforded
as a white solid (1.477 kg, yield 95%).
Isolated yield: 55% (22.3 kg; mp: 107.4 °C; potentio-
metric titre: 94%).
XPhos. In a 316-L reactor equipped with a mechanical
stirrer and a condenser is charged, under nitrogen, magne-
sium (1.3 kg) in 13.6 kg of anhydrous THF. The reaction
mixture is heated under reflux, and 0.12 kg of 1,2-
dibromoethane is then added to the reactor. 1-Bromo-2,4,6-
triisopropylbenzene (14.5 kg) and THF (20 kg) are simul-
taneously added slowly over an hour. The Grignard formation
is followed by GC, and the reaction is complete after an
hour of stirring.
The second crop of magnesium (1.3 kg) is added to the
reactor. The o-bromochlorobenzene (9.8 kg) is then intro-
duced dropwise over 3 h. Stirring is maintained an hour under
THF reflux until the formation of the diarylGrignard reaches
completion (reaction followed by GC).
The mixture is cooled to room temperature. Copper
chloride (0.485 kg) is added. The dicyclohexylphosphine
chloride (11.8 kg) is added dropwise over an hour to control
the exothermal, and the reaction mixture is stirred overnight
at room temperature.
The mixture is quenched with 37 kg of aqueous sodium
bisulfite and 30 L of water. The layers are separated. Thirty-
three kilograms of n-butanol are added in the organic layer.
THF is distilled, and the phosphine allows crystallising in
ethyl acetate at 0 °C for an hour. The solid is filtered and
rinsed with 2 × 20 kg of n-butanol. The phosphine is
afforded as white crystals.
Isolated yield: 56% (13.7 kg; mp: 185.9 °C; potentio-
metric titre: 96.7%).
MePhos. In a 316-L steel reactor equipped with a
mechanical stirrer and a condenser is charged, under nitrogen,
magnesium (3.2 kg) in 25.3 kg of anhydrous THF. The
Received for review September 7, 2004.
OP049832Y
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