A simple and new method for the synthesis of thiophosphates

Article abstract of DOI:10.1016/S0040-4039(02)02136-6

A simple, efficient, and general method has been developed for the synthesis of thiophosphates through a one-pot reaction of alkyl halides with the mixture of diethyl phosphite in the presence of ammonium acetate/sulfur and acidic alumina under solvent-fr

Full text of DOI:10.1016/S0040-4039(02)02136-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8713–8714
A simple and new method for the synthesis of thiophosphates
Babak Kaboudin*
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45195-159, Iran
Received 15 August 2002; revised 18 September 2002; accepted 26 September 2002
Abstract—A simple, efficient, and general method has been developed for the synthesis of thiophosphates through a one-pot
reaction of alkyl halides with the mixture of diethyl phosphite in the presence of ammonium acetate/sulfur and acidic alumina
under solvent-free conditions using microwave irradiation. © 2002 Elsevier Science Ltd. All rights reserved.
reactions for the synthesis of organophosphorus com-
pounds,15–18 we report here a new method for the
preparation of thiophosphates by reaction of diethyl
phosphite with alkyl halides in the presence of a mix-
ture of ammonium acetate/sulfur/alumina under sol-
vent-free conditions using microwave irradiation
produces high yields of thiophospates (Scheme 1, Table
1).
Organophosphorus compounds have found a wide
range of application in the areas of industrial, agricul-
tural, and medicinal chemistry owing to their biological
and physical properties as well as their utility as syn-
thetic intermediates.1 The synthesis of phosphate esters
is an important objective in organic synthesis, since
they have found use in the preparation of biologically
active molecules, and also versatile intermediate in syn-
thesis of amides and esters.2,3 Among the phosphate
esters, thiophosphate derivatives are of interest as effec-
tive pesticides.4 In recent years a number of thiophos-
As shown in Table 1, a wide range of alkyl halides in
the presence ammonium acetate/sulfur/alumina were
reacted with diethyl phosphite, giving the required
phates
have
been
introduced
as
potential
chemotherapeutic agent.5,6 Despite their wide range of
pharmacological activity, industrial and synthetic appli-
cations, the synthesis of thiophosphates has received
little attention. The following methods, not generally
applicable, have been reported in the literature: (i)
reaction of dialkyl phosphites with sulfenyl chlorides,7
sulfenyl cyanides,8 thiosulfonates,9 disulfides,10 and sul-
fur,11 (ii) condensation of phosphorchloridate with thi-
ols.12 However, all of these methods have problems,
include drastic reaction conditions and also some severe
side reactions. Surface-mediated solid phase reactions
are of growing interest13 because of their ease of set up
and work-up, mild reaction conditions, rate of the
reaction, selectivity, high yields, lack of solvent and the
low cost of the reactions in comparison with their
homogeneous counterparts. The application of
microwave energy to accelerate organic reactions is of
increasing interest and offers several advantages over
conventional techniques.14 Synthesis of molecules which
normally require large periods, can be achieved conve-
niently and very rapidly in a microwave oven. As a part
of our efforts to explore the utility of surface-mediated
Scheme 1.
Table 1. Reaction of diethyl phosphite with alkyl halides
in the presence mixture of ammonium acetate/sulfur/alu-
mina under solvent-free conditions using microwave irradi-
ation
2
R
X
Reaction time (min) Yield (%)a
a
a
b
c
d
e
f
PhCH2-
PhCH2-
Ph2CH-
PhCH2CH2-
p-NO2C6H4CH2- Br
p-MeC6H4CH2-
o-MeC6H4CH2-
Br
Cl
Br
Br
2
2
3
2
2
2
5
3
2
2
76
82
88
75
90
88
76
85
87
80
Cl
Cl
g
h
i
m-MeC6H4CH2- Cl
1-C10H7CH2- Cl
PhCH2CH2CH2- Cl
* Tel.: +98 241 4242239; fax: +98 241 4249023; e-mail: kaboudin@
iasbs.ac.ir
a Isolated yields.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02136-6

8714
B. Kaboudin / Tetrahedron Letters 43 (2002) 8713–8714
products 2 in excellent yields. The reactions were clean
with no tar formation. Ammonium formate
(NH4O2CH) is not as effective as ammonium acetate
and gave low yields of required product. Other ammo-
nium salts (NH4Cl, NH4Br, NH4PF6) are not effective
and didn’t give any product.
Crooke, S. T.; Bennett, C. F. Annu. Rev. Pharmacol.
Toxicol. 1996, 36, 107.
6. Elzagheid, M. I.; Mattila, K.; Oivanen, M.; Jones, B. C.
N. M.; Cosstick, R.; Lonnberg, H. Eur. J. Org. Chem.
2000, 1987.
7. Yoshido, M; Maeda, T.; Sugiyama, H. Japanese Patent
1541 (C1.16 C 92), 1967; Chem. Abstr. 1967, 66, 115455.
8. (a) Folkin, A.V.; Kolomiets, A. F.; Iznoskova, M. G. Izv.
Akad. Nauk. SSSR, Ser. Khim. 1974, 2837; Chem. Abstr.
1975, 82, 97323; (b) Schrader, G. U.S. Patent 2 597 534;
Chem. Abstr. 1953, 47, 4357h.
This solvent-free reaction method is operationally sim-
ple. 10 mmol of the reagent was prepared by the
combination of ammonium acetate (10 mmol, finely
ground), sulfur (10 mmol) and alumina (Al2O3, acidic,
2.5 g) in a mortar and pestle by grinding them together
until a fine, homogeneous, powder was obtained (5–10
min). Diethyl phosphite (10 mmol) was added to this
mixture and the mixture was irradiated by microwave
for 1 min using 720 W. The alkyl halide (9 mmol) was
added to this reagent (solid alkyl halides need to be
grinded) and was irradiated by microwave for 2-5 min
using 720 W (A kitchen-type microwave was used in all
experiments). Chromatography through a plug of silica
gel with EtOAc/n-hexane (1:9–5:5) and evaporation of
the solvent under reduced pressure gave the pure prod-
ucts as oils in 75–90% yields.19
9. Michalski, J.; Modro, T.; Wieczorkowski, J. J. Chem.
Soc. 1960, 1665.
10. (a) Michalski, J.; Wasiak, J. J. Chem. Soc. 1962, 5056; (b)
Michalski, J.; Wieczorkowski, J.; Wasiak, J.; Pliszka, B.
Rocz. Chem. 1959, 33, 247 Chem. Abstr. 1959, 53, 17884;
(c) Harvey, R. G.; Jacobson, H. I.; Jensen, E. V. J. Am.
Chem. Soc. 1963, 85, 1618.
11. (a) Sato, Z.; Takagi, K.; Imamiya, Y.; Shimizu, F.;
Kusano, S. Ger. Offen. 2 601 532 (C1. CO7F9/17), 1976;
Chem. Abstr. 1976, 85, 123628; (b) Hashimoto, T.;
Ohkubo, T. Japanese Patent 77 10 868 (C1. CO7F9/06);
Chem. Abst. 1977, 87, 134503; (c) Schrader, G.; Lorenz,
W. U.S. Patent 2 862 017, 1958; Chem. Abstr. 1960, 54,
1438a; (d) Farbenfabriken Bayer Akt.-Ges. British Patent
814332, 1959; Chem. Abstr. 1960, 54, 17330c; (e) Kabach-
nik, M. I.; Mastrykova, T. A. Zh. Obshch. Khim. 1955,
25, 1924; Chem. Abstr. 1956, 50, 8499d.
In summary, a simple work-up, low consumption of
solvent, fast reaction rates, mild reaction condition,
good yields, relatively clean with no tar formation the
reaction make this method an attractive and a useful
contribution to present methodologies. Indeed, a wide
range of alkyl halides was converted to corresponding
thiophosphates using this method.
12. (a) Schrader, G.; Lorens, W. German Patent 817 057 (C1.
45l, 3ol), 1951; Chem. Abstr. 1954, 48, 6643d; (b) Sall-
mann, R. Swiss Patent 324980, 1957; Chem. Abstr. 1958,
52, 14960a.
13. (a) Fadel, A.; Yefash, R.; Saluan, J. Synthesis 1987, 37;
(b) Rosini, G.; Galarini, R.; Marotta, E.; Righi, R. J.
Org. Chem. 1990, 55, 781; (c) Kodomari, M.; Sakamoto,
T.; Yoshitomi, S. J. Chem. Soc. Chem. Commun. 1990,
701; (d) Kropp, P. J.; Daus, K. A.; Crawford, S. D.;
Tubergren, M. W.; Kepler, K. D.; Craig, S. L.; Wilson,
V. P. J. Am. Chem. Soc. 1990, 112, 7433; (e) Hondrogian-
nis, G.; Pagni, R. M.; Kabalka, G. W.; Anisoki, P.; Kurt,
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Acknowledgements
The Institute for Advanced Studies in Basic Sciences
(IASBS) is thanked for supporting this work.
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with the assigned structures. For 2a (S-benzyl O,O-
diethyl phosphorothioate) as an example 1H NMR
(CDCl3/TMS-500 MHz): 1.31 (6H, t, J=7.1 Hz), 4.01–
4.25 (6H, m), 7.27–7.29 (5H, m); 31P NMR (CDCl3/
H3PO4-85%): 27.05 ppm; 13C NMR: 16.39, 35.4, 63.9,
128.0, 129.1, 137.9; IR (neat): 1260 (PꢀO), 1162(PꢁOꢁEt)
cm−1
.