Curphey
combined, refluxed, and stirred magnetically. At intervals, an
aliquot of the reaction mixture was withdrawn, added to a
measured volume of methanol to give a solution at a nominal
1 mM concentration, and analyzed by HPLC. Yields were
determined by comparing the area of the product peak to an
authentic sample at 1 mM concentration. When the reaction
was judged to be complete, the reaction mixture was processed
in one of two ways. For runs where the objective was only to
obtain yields and not to prepare the thionation product, the
reaction mixture was made to a known volume in a volumetric
flask. An aliquot of this solution was diluted in methanol to 1
mM nominal concentration and reanalyzed by HPLC to obtain
the chromatographic yields reported in the tables. For runs
whose objective was the preparation of the thionation product,
the reaction mixture was worked up by one of the procedures
described below without redetermining the final yield. The
reaction times reported in the tables were those at which the
yield of product appeared to be no longer increasing. Because
of sampling errors (estimated at 2-3%), solvent evaporation,
and the subjectivity involved in deciding when yields were no
longer increasing, the times in the tables should be regarded
as approximate.
Meth od B. For some substrates, particularly the 3-oxo-
esters, the above procedure was modified by adding the
carbonyl compound over a 2-5 min period to the refluxing
mixture of the other components. This was done because the
vigorous reaction of these substrates with P4S10 can be difficult
to control on a large scale if all components are first combined
at room temperature and then heated. Comparison of small-
scale reactions run both ways showed no significant difference
in yield.
Th ion a tion s w ith P 4S10 a n d LR. Thionations with P4S10
alone were run identically to those with P4S10/HMDO (general
thionation procedure, method A or B), omitting the HMDO.
Thionations with LR were conducted as described in the
literature, the standard experiment employing 3 mmol of
substrate in 3 mL of solvent. For esters and lactones 21a and
22a , 3.6 mmol LR was used.16,41 For other lactones and for all
amides and lactams, 1.5 mmol of LR was used.15,23,29 For
ketones, 1.8 mmol of LR was used,31,33 while for 3-oxoesters, 6
mmol of LR was used.11 Details of solvent, temperature, and
reaction times are to be found in Tables 2, 3, 5, 6, and 7.
Reactions were sampled for HPLC analysis as for the general
thionation procedures.
R ea ct ion Wor k u p P r oced u r es. Met h od A: Aq u eou s
K2CO3. The reaction mixture was cooled to 0 °C and aqueous
K2CO3 solution (1.26 mL of 5.3 M/mmol of P4S10 taken) was
added. For reaction solvents immiscible with water, a volume
of acetone equal to one-half of the reaction solvent was added,
while for reaction solvents miscible with water additional
water (1 mL/mmol of P4S10 taken) was added to obtain a
stirable mixture. The reaction mixture was stirred vigorously
for 30 min at 0 °C. Water and an extraction solvent were
added, the layers were separated, and the organic phase was
washed with dilute K2CO3 solution, water, and brine. The
organic extract was dried over MgSO4 or Na2SO4 and evapo-
rated, and the crude product was purified as indicated.
tion solvent were added, and the mixture then processed as
for method A.
Met h od C: Aq u eou s Na 2H P O4. The reaction mixture
was cooled to room temperature and, for reaction solvents
immiscible with water, a volume of acetone equal to one-half
of the reaction solvent was added. Water (2 mL/mmol of P4S10
taken) and finely powdered Na2HPO4 (1.14 g or 8 mmol/mmol
of P4S10 taken) were added and the mixture was stirred
vigorously for 1-2 h. If desired, the progress of the reaction
may be followed by 1H NMR, monitoring the disappearance
of peaks in the δ 0.3 region due to the TMS thiophosphates.
When hydrolysis was complete, water and an extraction
solvent were added, and the mixture then processed as for
method A.
Meth od D: F iltr a tion th ou gh Silica Gel. The reaction
mixture was concentrated under reduced pressure to a small
volume, dissolved in the appropriate solvent, and passed
through a column of silica gel (20 g/mmol of P4S10 taken). The
usual flash chromatography setup may be used, or the gel may
be supported on a funnel. After evaporation of the eluate, the
product was purified further as indicated.
O-Meth yl Ben zen eca r both ioic Acid (5b). The reaction
was carried out for 10 h according to the general thionation
procedure, method A, with 5a (3.73 mL, 30 mmol), P4S10 (4.45
g, 10 mmol), HMDO (10.6 mL, 50 mmol), and xylene (30 mL).
Workup by the reaction workup procedure, method A, with
benzene as the extraction solvent, followed by distillation gave
5b (3.63 g, 79%) as an orange liquid, bp 62-65 °C/0.25 Torr
(lit.16 bp 110-112 °C/10 Torr). Purity by GC was 99.5%.
Dih yd r o-5-m eth yl-2(3H)-fu r a n th ion e (18b). The reac-
tion was carried out for 1.5 h according to the general
thionation procedure, method A, with 18a (4.74 mL, 50 mmol),
P4S10 (5.56 g, 12.5 mmol), HMDO (17.7 mL, 83 mmol), and
acetonitrile (50 mL). Workup by the reaction workup proce-
dure, method A, with ethyl acetate as extraction solvent gave
a crude liquid that was dissolved in 2:1 hexane/toluene, filtered
through silica gel, and distilled to give 18b (4.53 g, 78%) as a
yellow liquid, bp 39-42 °C/0.02 Torr (lit.23 bp 125-127 °C/30
Torr). Purity by GC was 99.8%.
5-Meth yl-3H-1,2-d ith iole-3-th ion e (24a ). The reaction
was carried out for 1 h according to the general thionation
procedure, method B, with 23a (3.19 mL, 25 mmol), P4S10 (6.67
g, 15 mmol), sulfur (0.802 g, 25 mg atom), HMDO (16 mL, 75
mmol), and xylene (50 mL). Workup by the reaction workup
procedure, method A, with toluene as extraction solvent gave
a dark oil, which was dissolved in toluene, filtered through a
column of silica gel (11 g) plus activated carbon (7.4 g), and
recrystallized from CCl4 to give 24a (2.95 g, 80%) as large
orange needles, mp 34-35 °C (lit.48 mp 33 °C). Purity by HPLC
was 99.0%.
Ben zen eca r both ioa m id e (25b). The reaction was carried
out for 20 min according to the general thionation procedure,
method A, with 25a (0.363 g, 3 mmol), P4S10 (0.253 g, 0.57
mmol), HMDO (1.06 mL, 5 mmol), and dichloromethane (3
mL). Workup by the reaction workup procedure, method D,
with dichloromethane as eluent, followed by recrystallization
from benzene/cyclohexane gave 25b (0.329 g, 80%), mp
117-118 °C (lit.15 mp 118 °C). HPLC showed no detectable
impurities.
Meth od B: Meth a n olic K2CO3. A mechanical stirrer was
used because of the formation of thick salt suspensions that
cannot be adequately stirred magnetically. The reaction
mixture was cooled to 0 °C and finely powdered K2CO3 (0.921
g or 6.67 mmol/mmol of P4S10 taken) was added. Methanol
(1.67 mL/mmol of P4S10 taken) was added cautiously dropwise,
monitoring gas evolution via the mineral oil bubbler, until a
vigorous gas evolution ensued. When this subsided, the
remainder of the methanol was added rapidly. The mixture
was vigorously stirred at 0 °C until gas evolution had ceased,
which generally required 30 to 45 min. Water and an extrac-
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