Coumaphos-d10 and Related Compounds
J. Agric. Food Chem., Vol. 48, No. 7, 2000 2827
MATERIALS AND METHODS
magnetic stirring. A sample taken after 4 h indicated the
disappearance of starting materials by GLC. The mixture was
filtered, and the filtrate was concentrated on a rotary evapora-
tor to give a brownish yellow oil, which promptly solidified.
The solid was dissolved in MTBE (125 mL, heating was
required; a yellow gum remained undissolved, but dissolved
on the addition of sodium carbonate solution) washed three
times with saturated sodium carbonate solution (∼60 mL each)
and once with water. The combined aqueous phases were
extracted once with MTBE, and the combined organic phases
were dried with MgSO4 and a little activated charcoal. After
filtration, solvent removal left 9.6 g of an off-white powder still
containing a little MTBE. The crude product was recrystallized
from MTBE (50 mL total volume) to give a white powder (the
outside of the filter cake was pale yellow): 8.29 g (93.8%), mp
92.5-93.5 °C, >99% pure by GLC, 15.185 min; MS 374 (39),
373 (17), 372 (100), 342 (16), 340 (40), 308 (15), 229 (34), 227
(92), 211 (48). Concentration of the mother liquor gave a second
crop of a pale yellow powder: 264 mg (3%), mp 90-91.8 °C
(∼97% pure by GLC). A coumaphos analytical standard
(Chemagro, now Bayer Animal Health, Shawnee Mission, KS),
nominally 99.7% pure, melted at 92.5-94 °C (lit., 95 °C;
Schrader, 1954); GLC 15.213 min; MS 364 (38.5), 363 (16), 362
(100), 336 (17), 334 (44), 306 (22), 228 (26), 226 (64), 210 (36.5).
Phosphorus pentasulfide and all organic starting materials
were obtained from Aldrich Chemical Co. All calculations are
based on phosphorus pentasulfide as P2S5 rather than P4S10
Benzene was dried by azeotropic distillation (Dean-Stark
trap). Chlorine was obtained in a lecture bottle from Air
Products. Methyl tert-butyl ether (MTBE, high-purity grade)
was obtained from Arco Chemical Co. and used without further
purification. Glassware was dried overnight or longer at 120
°C.
.
Gas chromatography was carried out on a Hewlett-Packard
5890 series II instrument with a 15 m × 0.53 mm DB-1 column
(J &W Scientific, Folsom, CA). The column was held at 50 °C
for 2 min, programmed at 15 °C/min to 300 °C, and held at
300 °C for 20 min, although the program was frequently
terminated manually after the compounds of interest eluted.
GLC-MS was performed on a Finnigan MAT GLCQ instru-
ment with a Restek Rtx-5MS column (30 m, 0.25 mm i.d., 0.25
µm df, column head pressure ) 0.9 bar, Restek Corp., Belle-
fonte, PA). The initial column temperature of 60 °C was held
for 1 min, and then the temperature was raised 20 °C/min to
270 °C and held at 270 °C for 14.5 min (total run time ) 26
min).
Proton and 13C NMR spectra were recorded in CDCl3 on a
Bruker QE 300 instrument with a Mac NMR v5 data system.
All proton and 13C spectra were consistent with expected
structures.
Syn th esis of P ota sa n -d 10 (2-d ). This material was syn-
thesized according to essentially the same method as was
coumaphos-d10, starting with 7-hydroxy-4-methylcoumarin
(3.52 g, 20 mmol), potassium carbonate (5 g, 36 mmol), and
diethyl chlorothiophosphate-d10 (3.97 g, 20 mmol) in acetone
(75 mL), heated under reflux for 4.5 h. After filtration, removal
of acetone, partitioning between sodium carbonate solution and
MTBE, drying, and solvent removal, the resulting pale yellow
oil (7.63 g) was crystallized from pentane/MTBE (10 mL each)
to give white platelets (5.29 g, 78%): mp 35-36.5 °C; GLC
14.306 min; MS 339 (9), 338 (58.5), 306 (26), 274 (13.5), 194
(15), 193 (100), 191 (13), 177 (29), 165 (11), 149 (21). Unlabeled
potasan, prepared similarly, had mp 36-38 °C (lit., 38 °C;
Schrader, 1952); GLC 14.345 min; MS 329 (19), 328 (91.6), 300
(36), 272 (24), 193 (13), 192 (100), 187 (25.5), 176 (37), 164
(13), 148 (25).
Syn th esis of Dieth yl Ch lor oth iop h osp h a te-d 10 (3). A
100 mL pear-shaped flask was fitted with a Claisen adapter
equipped with a septum inlet and a condenser with a drying
tube (Drierite). To the flask were added phosphorus penta-
sulfide (10.6 g, 48 mmol) and benzene (15 mL). The slurry was
stirred magnetically and heated to reflux. To the slowly
refluxing solution was added ethanol-d6 (99+ atom % D, 9.948
g, 182 mmol, net contents of the ampules were somewhat below
label amount) dropwise from a syringe over 30 min. A steady
release of H2S occurred during the addition, and most of the
solid P2S5 dissolved. When all of the ethanol was added, the
solution was heated at reflux for a further 2 h (most of the
remaining solid dissolved, and the solution turned a dull green)
and then cooled to room temperature.
Chlorine (5.5 mL, 122 mmol) was distilled from the cylinder
and condensed into a 15 mL graduated centrifuge tube, which
was cooled in a cold (∼-100°, Cryo-Cool CC-100 II, Neslab
Inc, Portsmouth, NH) methanol bath. The flask containing the
diethyldithiophosphoric acid was placed in a water bath, and
ice was added occasionally to the bath to maintain it at ∼15
°C. The tube containing chlorine was fitted with a distillation
head consisting of a right-angle adapter, a short piece of Tygon
tubing, and a disposable Pasteur pipet. The chlorine was then
distilled into the solution over 15-20 min, regulating the rate
of distillation by cooling the tube as necessary with chilled
methanol from the cold bath. The green color disappeared
during the addition, and the solution became a clear orange-
yellow. After an additional 20 min of stirring, the solution of
diethyl chlorothiophosphate-d10 and sulfur monochloride was
added over 30 min to water (40 mL) magnetically stirred in a
125 mL Erlenmeyer flask. After the addition was complete,
the suspension was stirred for an additional 15 min and
RESULTS AND DISCUSSION
The yield in the preparation of the labeled diethyl
chlorothiophosphate (78%) and the yield of a practice
run using unlabeled ethanol (80.3%) were similar and
superior to the yields of 50-65% obtained by Fletcher
et al. (1950), and these authors report that the reaction
is general. Yields of crude coumaphos and potasan were
essentially quantitative; most losses occurred during
recrystallization of the product insecticides. Both labeled
pesticides crystallized well and had good GLC proper-
ties. In all cases, however, the deuterated material
eluted from GLC slightly (0.03-0.04 min for the thio-
phosphates, 0.07 min for the acid chloride) before the
unlabeled material, at least on the relatively nonpolar
columns we used.
filtered through
a pad of Celite to remove the gummy
This sequence and analogous reactions starting with
other deuterated alcohols, particularly methanol-d4,
could be used for the synthesis of other deuterium-
labeled dialkyl thiophosphates such as parathion, par-
athion-methyl, and azinphos-methyl, etc. The number
of deuterium atoms is sufficient to raise the molecular
weight well above the isotope cluster for the unlabeled
compound, making independent analysis of the internal
standard and the undeuterated analyte possible and the
use of such deuterated compounds as internal standards
for mass spectrometric analysis quite attractive. Other
deuteration patterns such as CD3CH2- are also pos-
sible, but the starting alcohols are more expensive.
precipitate of sulfur. The organic layer was removed, and the
aqueous phase was extracted once with MTBE. The organic
phases were combined, washed once with water, dried (Mg-
SO4), and concentrated on a rotary evaporator. The resulting
brownish oil (16.4 g) was distilled [bp 100-101.5 °C/35 mm,
lit. (undeuterated compound bp 94-96 °C/20 mm; Fletcher et
al., 1950)] to give a colorless oil, 14.065 g (78%), GLC 4.320
min (unlabeled 4.393 min). The pot residue seemed to be
mostly sulfur.
Syn th esis of Cou m a p h os-d 10 (1-d ). The deuterated acid
chloride (5.04 g, 25.4 mmol) was added to a slurry of 3-chloro-
4-methyl-7-hydroxycoumarin (5.34 g, 25.4 mmol) and pow-
dered anhydrous potassium carbonate (6.35 g, 46 mmol) in
acetone (75 mL). The mixture was heated at reflux with
Kochansky, Jan
