Thermal Fragmentation of Phosphoramidothioates
J . Org. Chem., Vol. 61, No. 12, 1996 3949
(H+) in acetone and washed with acetone until the eluate was
colorless. A solution of 2.00 g (8.5 mmol) of sodium salt 8 in
10 mL of acetone was placed on the column and washed
through with 150 mL of acetone. Solvent was stripped from
the eluate, the residue was taken up in 10 mL of toluene, and
the solvent was again stripped until the appearance of either
crystals or oil. Several drops of toluene were then added, and
the solution was kept at -15 °C overnight. The crystalline
product was washed with a little cold toluene and then hexane.
Reprocessing of the filtrates gave a second crop of crystals.
The total yield of 9 was 1.22 g (73%): mp 74-75 °C; 31P NMR
(CDCl3) δ 65.7; 1H NMR similar to that of 8 with δ 1.32, 1.33,
3.31, 4.16. Anal. Calcd for C6H16NO2PS: C, 36.53; H, 8.18;
N, 7.10. Found: C, 36.77; H, 8.29; N, 7.14.
methylphosphinic acid also gave strong signals attribut-
able to pyro structure 34 (PdS, δ 47.7; PdO, δ 44.6; 2J PP
) 28.8 Hz); unidentified contaminants (5-10% of total
signal intensity) had signals at δ 43.4 and 54.7. If
isolation procedures could be developed, the thiophos-
phorylation method could have practical value for the
synthesis of mixed thiophosphate-phosphinate pyro
structures.
Syn t h esis of O-E t h yl N-Ad a m a n t ylp h osp h or a m id o-
ch lor id oth ioa te (12). A solution of 8.73 g (0.058 mol) of
adamantylamine and 17.6 g (0.173 mol) of triethylamine in
60 mL of toluene was dropped during a 70 min period into a
chilled (ice water) solution of 12.7 g (0.087 g) of ethyl phos-
phorodichloridite in 130 mL of toluene. Stirring and a nitrogen
blanket were provided. After an additional hour at 0 °C and
then 1 h at room temperature, the mixture containing 11 was
treated with sulfur (5.2 g, 0.163 mol) and heated at 80 °C for
4 h. The mixture was filtered, and the residue was washed
twice with 50 mL of toluene. The solvent was removed from
the filtrates, and the residue was taken up in 200 mL of
acetone. Some unreacted sulfur separated and was removed.
The solvent was stripped, and the residue was extracted with
50 mL of ethyl acetate-hexane (1:4). The extract was passed
through a silica gel column (2.5 × 30 cm) with the same solvent
mixture. The recovered solid was dissolved in the minimum
amount of chloroform (15 mL), a few milliliters were removed
by evaporation, and the solution was then treated with 300
mL of hexane. White crystals formed overnight in the freezer.
They were collected and washed with hexane. The mother
liquor was preserved for later hydrolysis to 13 (vide infra).
The recrystallized (chloroform-hexane) solid 12 (2.99 g, 17.6%)
had the following: mp 120-122 °C; 31P NMR (CDCl3) δ 67.2;
The thiophosphorylation of two phosphonic acids (meth-
yl and phenyl) was less satisfactory. Numerous signals
were observed on the 31P NMR spectra, along with those
expected for the pyro products. The mixtures do not
appear attractive for isolation studies.
This brief survey of thiophosphorylation of acidic
phosphorus compounds therefore showed that the method
could have practical value in the case of phosphoric and
phosphinic acid derivatives and deserves further develop-
ment. The synthesis of thiophosphoryl derivatives of
nucleotides is a possibility that also deserves attention.
An advantage of our new method is that a dialkyl ester
can be synthesized; monothiopyrophosphates are rather
well-known as the tetraalkyl esters,20 but partially es-
terified derivatives are rare.
Exp er im en ta l Section 21
Syn t h esis of O-E t h yl N,N-d iet h ylp h osp h or a m id o-
ch lor id oth ioa te (7). O-Ethyl phosphorothioic dichloride
(35.8 g, 0.20 mol) was stirred vigorously at -15 °C while it
was treated simultaneously with 14.5 g (0.20 mol) of diethyl-
amine and a solution of 7.9 g (0.20 mol) of NaOH in 30 mL of
water in separate dropping funnels. The mixture was stirred
an additional 2 h at about 0 °C and then washed successively
with 100 mL of water, 100 mL of saturated NaHCO3, and 100
mL of water. The organic phase was dried over anhydrous
MgSO4 and vacuum distilled. The product 7 (11.2 g, 64%) was
collected at 95-100 °C at 3 mmHg (lit.18 bp 105-106 °C at 10
3
4
1H NMR (CDCl3) δ 1.40 (d of t, J HH ) 7.1 Hz, J PH ) 0.7 Hz,
3 H), 1.66 (m, 6 H), 2.00 (m, 6 H), 2.1 (m, 3 H), 3.45 (br d, 2J PH
) 14.3 Hz, 1 H), 4.25 (m, 2 H). Anal. Calcd for C12H21
-
ClNOPS: C, 49.06; H, 7.21; N, 4.74. Found: C, 49.27; H, 7.11;
N, 4.84.
Syn th esis of Sod iu m O-Eth yl N-Ad a m a n tylp h osp h or a -
m id oth ioa te (13). A solution of 2.95 g (0.010 mol) of 12 in
120 mL of acetone was stirred with a solution of 0.80 g (0.02
mol) of NaOH in 30 mL of water for 1 h at room temperature.
The acetone was stripped, and the remaining water solution
was washed twice with 50 mL of chloroform. The water layer
was evaporated to dryness, and the residue was taken up in
acetone. Insoluble NaCl was filtered off, and the filtrate was
evaporated to dryness. The residual oil was dissolved in 300
mL of ether; the salt 13 crystallized overnight. A second crop
was obtained by evaporating the mother liquor and taking up
the residue in 150 mL each of ether and hexane. The combined
solids of 13 were recrystallized from methanol-ether (2.85 g,
85.4%): 31P NMR (CDCl3) δ 53.2; 1H NMR (CD3OD) δ 1.24 (t,
3J HH ) 7.1 Hz, 3 H), 1.65 (m, 6 H), 1.91 (m, 6 H), 1.99 (m, 3
H), 3.92 (m, 2 H). Anal. Calcd for C12H21NNaO2PS‚2H2O: C,
43.24; H, 7.56; N, 4.20. Found: C, 43.96; H, 7.47; N, 4.32.
Syn t h esis of O-E t h yl N-Ad a m a n t ylp h osp h or a m id o-
th ioa te (14). The sodium salt 13 (1.70 g, 5.1 mmol) in 15 mL
of methanol was passed through a column of 16 g of prewashed
Amberlyst 15. The acid 14 was eluted with 200 mL of
methanol, and the solvent was stripped to leave a thick
residual oil. This was dissolved in about 8 mL of ether and
treated with 200 mL of hexane. Acid 14 crystallized overnight
in the freezer. It was collected, washed with hexane, and dried
over P2O5 in a vacuum desiccator (1.22 g, 87.1%): mp 124-
124.5 °C; 31P NMR (CDCl3) δ 61.3; 1H NMR (CDCl3) δ 1.35 (t,
3J HH ) 7.1 Hz, 3 H), 1.64 (m, 6 H), 1.98 (m, 6 H), 2.07 (m, 3
H), 3.5 (br s), 4.13 (m, 2 H). Anal. Calcd for C12H22NPO2S:
C, 52.34; H, 8.06; N, 5.09. Found: C, 52.60; H, 8.19; N, 4.96.
Additional 14 could also be obtained from the mother liquor
using the crystallization procedure of 12 described earlier. This
was accomplished by evaporation of the mother liquor to a
1
mmHg): 31P NMR (benzene) δ 75.0; H NMR (CDCl3) δ 1.17
3
3
(t, J HH ) 7.1 Hz, 6 H, NCH2CH3), 1.37 (d of t, J HH ) 7.1 Hz,
4J PH ) 0.9 Hz, OCH2CH3), 3.34 (m, 4 H, NCH2CH3), 4.21 (m,
2 H, OCH2CH3).
Syn th esis of P otassiu m O-Eth yl N,N-dieth ylph osph or a-
m id oth ioa te (8). To a solution of 5.2 g (0.92 mol of KOH in
300 mL of acetone-water (2:1)) was added 10.0 g (0.046 mol)
of 7. The solution was kept at 30-35 °C while it was stirred
for 3 days. The solvent was then removed with a rotary
evaporator, and the residue was extracted with 200 mL of
acetone. The extract was again evaporated to leave an oil,
which was redissolved in 10 mL of acetone and diluted with
300 mL of ether. Crystals formed after overnight chilling; a
second crop was obtained by duplicating the procedure with
smaller solvent volumes. The procedure was performed a total
of six times, yielding 8.2 g (75%) of white crystals, mp 179-
180 °C (lit.19 mp 163-165 °C). The structure was confirmed
by 31P NMR (d6-acetone) δ 60.8 and 1H NMR (d6-acetone) δ
3
3
1.03 (t, J HH ) 7.0 Hz, 6 H), 1.17 (t, J HH ) 7.1 Hz, 3 H), 3.20
(m, 4 H), 3.74 (m, 2 H).
Syn th esis of O-Eth yl N,N-d ieth ylp h osp h or a m id oth io-
a te (9). A column was prepared with 15 g of Amberlyst 15
(19) Fletcher, J . H.; Hamilton, J . C.; Hechenbleikner, I.; Hoegberg,
E.; Sertl, B. J .; Cassaday, J . T. J . Am. Chem. Soc. 1948, 70, 3943.
(20) Michalski, J .; Reimschu¨ssel, W.; Kaminski, R. Russ. Chem. Rev.
1978, 47, 814.
(21) Instruments and general techniques are described in refs 1 and
22.