N,N-Dichloro poly(styrene-co-divinyl benzene) sulfonamide polymeric beads: an efficient and recyclable reagent for the synthesis of dialkyl chlorophosphates from dialkylphosphites at room temperature

Article abstract of DOI:10.1016/j.tetlet.2008.09.044

An efficient and operationally simple method is developed for the synthesis of dialkyl chlorophosphates from dialkylphosphites using a new chlorine bearing reagent, N,N-dichloro poly(styrene-co-divinyl benzene) sulfonamide in the form of polymeric beads. The reagent afforded dialkyl chlorophosphates at room temperature, and is recyclable.

Full text of DOI:10.1016/j.tetlet.2008.09.044

Tetrahedron Letters 49 (2008) 6704–6706
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
N,N-Dichloro poly(styrene-co-divinyl benzene) sulfonamide polymeric
beads: an efficient and recyclable reagent for the synthesis of dialkyl
chlorophosphates from dialkylphosphites at room temperature
Hemendra K. Gupta, Avik Mazumder, Prabhat Garg, Pranav K. Gutch, Devendra K. Dubey *
Vertox Laboratory, Defence Research and Development Establishment, Gwalior, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 July 2008
Revised 7 September 2008
Accepted 10 September 2008
Available online 13 September 2008
An efficient and operationally simple method is developed for the synthesis of dialkyl chlorophosphates
from dialkylphosphites using a new chlorine bearing reagent, N,N-dichloro poly(styrene-co-divinyl ben-
zene) sulfonamide in the form of polymeric beads. The reagent afforded dialkyl chlorophosphates at room
temperature, and is recyclable.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Dialkylphosphite
Dialkyl chlorophosphate
Polymer-supported-synthesis
1
5
16
17
18
,19
perch-
Organophosphorus compounds have attracted the attention of
researchers because of their wide applications in industrial, agri-
cultural, biochemical, and medicinal areas.1 Naturally occurring
organophosphorus compounds play an important role in the main-
tenance of life processes.2 It is interesting to note that chemical,
physical, and biological properties of organophosphorus com-
pounds are governed by the stereochemical disposition of substit-
uents around the phosphorous atom. One such class of compounds
is the dialkyl chlorophosphates. These chlorophosphates are used
for the transformation of various functional groups.7–12 Recently,
diethylchlorophosphate has been used as an efficient reagent in
such as elemental chlorine, phosgene, SO
2
Cl
2
,
S
2
Cl
2
,
SCl
2
2
0
21
22
23
24
25
CCl
4
,
CCl
3
NO
2
,
PhSO
2
NCl
2
,
2
C Cl
6
,
ClSCCl
3
,
2
CuCl ,
26
27
lorofulvalene, and N-chlorosuccinimide. Among these proce-
dures, only a few can be considered as convenient laboratory
methods for the synthesis of dialkyl chlorophosphates. Most of
these reported methods either use reagents or produce undesired
by-products, which are difficult to remove from the sensitive chlo-
while others are time consuming, involve
expensive and unstable reagents, and require harsh conditions. A
modified method (the so-called Atherton–Todd method) makes
–6
1
5–20
rophosphates,
4
use of CCl and a tertiary base to generate dialkyl chlorophosphates
in situ, but it has limited scope in the formation of P–N com-
pounds. Our aim in this research work was to overcome the lim-
1
3
cyclization reactions
and in regioselective ring opening of
1
4
8d
epoxides.
Methods described in the literature for the preparation of dial-
kyl chlorophosphates, involve chlorination of the corresponding
phosphites (dialkylphosphites/trialkylphosphites) with reagents
itations and drawbacks of the reported methods.
In recent years, the use of recyclable reagents has received con-
siderable interest in organic synthesis. This prompted us to explore
O
O
RO
RO
2
P
H
+
SO NCl2
2
SO NH2
2
2
P Cl
+
RO
RO
=
PS - DVB resin
Scheme 1. Dialkyl chlorophosphates prepared from dialkylphosphites using the polystyrene divinylbenzene (PS-DVB) bound reagent.
*
Corresponding author. Tel.: +91 751 2233488; fax: +91 751 2341148.
E-mail address: dkdubey@rediffmail.com (D. K. Dubey).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.044

H. K. Gupta et al. / Tetrahedron Letters 49 (2008) 6704–6706
6705
Table 1
the possibility of using the stable, nontoxic, recyclable, and
Isolated yields of dialkyl chlorophosphates from the reaction of dialkylphosphites and
N,N-dichloro poly(styrene-co-divinyl benzene) sulfonamide polymeric beads
efficient positive chlorine releasing reagent, N,N-dichloro poly(sty-
a
28
rene-co-divinyl benzene) sulfonamide polymeric beads. It has
Entry
R
31P NMR
(ppm)
Time
(h)
Yield
(%)
B.P
been incorporated as a reactive ingredient in a formulation devel-
oped in our laboratory to decontaminate bis(2-chloroethyl) sulfide
(°C/(mm/Hg))
(°C/(mm/Hg))
2
9
1
2
3
4
5
6
7
8
9
CH
3
6.34
5.04
5.48
3.76
4.58
4.16
4.71
4.59
3.58
4.25
4.7
2.00
2.00
2.30
2.30
2.30
2.30
2.30
3.00
3.00
3.15
3.15
3.45
95
96
97
96
94
95
92
94
96
98
94
93
75–77/20
85–87/10
102–103/10
90–92/10
115–117/10
122–124/10
140–142/5
131–132/1
122–124/1
Undistilled
Undistilled
140–142/1
(sulfur mustard), a chemical warfare agent. Having established a
commercially synthetic procedure for N,N-dichloro poly(styrene-
co-divinyl benzene) sulfonamide polymeric beads, we investigated
its use as an alternative reagent for the conversion of dial-
kylphosphites to dialkyl chlorophosphates and report our results
herein.
C
C
2
H
H
3
3
7
i-C
3
H
7
9
C
4
H
9
i-C
sec-C H
4 9
4
H
C
5
H
11
11
13
This development enables us to obtain almost all quantitative
yields of products in short reaction times. The room temperature
(20–25 °C) reaction of various dialkylphosphites with N,N-dichloro
poly(styrene-co-divinyl benzene) sulfonamide polymeric beads
afforded the corresponding dialkyl chlorophosphates in 3–4 h in
excellent yields (Scheme 1, Table 1).
i-C
5
H
10
11
12
C
C
C
6
6
6
H
H
H
5
5
CH
2
6.2
a
All products gave satisfactory NMR and GC–MS data and compared well with
authentic samples. 31P NMR spectra were recorded in CDCl
at 162 MHz.
3
The important aspect of this method is its simplicity. N,N-Di-
chloro poly(styrene-co-divinyl benzene) sulfonamide polymeric
beads were suspended in a suitable solvent, for example, acetoni-
trile. To this suspension, the dialkylphosphite (an equivalent
amount to the active chlorine available on the PS-DVS beads)
was added, and the mixture was stirred gently using a magnetic
3
0
stirrer. The reaction was monitored by removing an aliquot and
analyzing by GC–MS. The progress of a typical reaction as moni-
tored by GC–MS is depicted in Figure 1.
When all the dialkylphosphite had been consumed, the reaction
was decanted, and the beads were washed with solvent. After
removing the solvent by distillation, the products were obtained
in pure form by vacuum distillation. The yields and boiling points
of the products are summarized in Table 1. The PS-DVB beads were
recovered and re-chlorinated using the reported method.29 These
beads could be reused for the preparation of dialkylchlorophos-
phates. Thus, the advantages of this method are room temperature
reactions, simple workups, and recyclability of the reagent. We
found that both alkyl and aryl phosphates reacted efficiently at
room temperature to produce the corresponding chlorophosphates
in excellent yields. Aliphatic dialkylphosphites reacted a little more
rapidly compared to aromatic phosphites (entries 1–11 vs 12,
Table 1).
In conclusion, we have described an efficient reagent for the
rapid and convenient conversion of dialkylphosphites to dialkyl
chlorophosphates under mild conditions using N,N-dichloro
poly(styrene-co-divinyl benzene) sulfonamide polymeric beads,
as a stable and non-toxic reagent at room temperature.
References and notes
1.
(a) Eto, M. Organophosphorous Pesticides, Organic and Biological Chemistry; CRC
Press: USA, 1974; (b) Van Wazer John, R. In Phosphorous and its Compounds;
Interscience: New York, 1961; Vol. II; (c) Engel, R. Chem. Rev. 1977, 77, 349; (d)
Corbridge, D. E. C. Studies in Inorganic Chemistry 10, Phosphorous, an Outline of its
Chemistry, Biochemistry and Technology, 4th ed.; Elsevier Science: New York,
1990.
2.
3.
4.
5.
6.
Welber, M. Protein Phosphorylation; Pion: London, 1979.
Ramirez, F.; Marecrk, J. F. Chem. Res. 1978, 11, 239.
Lipman, F. Wandering of a Biochemist; Wiley: New York, 1971.
Hinkle, P.; McCarty, R. E. Sci. Am. 1978, 238, 104.
Clayton, R. K. Photosynthesis: Physical, Mechanism and Chemical Patterns;
Cambridge University Press, 1980.
7
.
.
Kosolapaff, G. M. In Organic Phosphorous Compounds; Wiley-Interscience: New
York, 1950; Vol. 6; p 503.
(a) Di Novi, M.; Trainor, D. A.; Nakanishi, K. Tetrahedron Lett. 1993, 24, 855; (b)
Audrieth, L. E.; Smith, W. C. J. Org. Chem. 1953, 18, 1288; (c) Nilsson, J.;
Stawinski, J. Chem. Commun. 2004, 2566; (d) Atherton, F. R.; Openshaw, H. T.;
Todd, A. R. J. Org. Chem. 1945, 10, 660; (e) Eakin, R. E. J. Am. Chem. Soc. 1955, 77,
8
1806; (f) Froehler, B. C. Tetrahedron Lett. 1986, 27, 5575; (g) Kers, I.; Stawinski,
J.; Girardet, J. L.; Imbach, J. L.; Perigaud, C.; Gossclin, G.; Aubertin, A. M.
Nucleocides Nucleotides 1999, 18, 2317; (h) Goodchild, J. In Oligonucleocides-
Antisense Inhibitors of Gene Expression; Cohen, J. S., Ed.; Macmillan Press Ltd,
Figure 1. Progress of a typical reaction as monitored by GC–MS analysis at different
time intervals.
1989; Vol. 12, p 53.

6
706
H. K. Gupta et al. / Tetrahedron Letters 49 (2008) 6704–6706
9
.
Shi, E.; Pei, C. Synthesis 2004, 2995.
19. Poshkus, A. C.; Herweh, J. E. J. Am. Chem. Soc. 1962, 84, 555.
1
0. (a) Larson, E.; Lining, B. Tetrahedron Lett. 1994, 35, 2737; (b) Xiao, Q.; Sun, J.;
20. Stein, S. S.; Koshland, D. E. Arch. Biochem. Biophys. 1952, 39, 229.
21. Kamai, G. Dokl. Akad. Nauk. SSSR 1951, 79, 795. Chem. Abstr. 1952, 46,
6081f.
Sun, Q.; Ju, J.; Zhao, Y. X. Synthesis 2003, 107; (c) Zamyatina, A. Y.; Bushnev, A.
S.; Shvets, V. I. Bioorg. Khim. 1994, 20, 1253.
1
1
1. Whitehead, A.; Moore, J. D.; Hanson, P. R. Tetrahedron Lett. 2003, 44, 4275.
2. Nicolaou, K. C.; Yang, Y.; Ouellette, M.; Shi, G. O.; Gaertner, P.; Gunzner, J. L.;
Agrios, C.; Huber, R.; Chadha, R.; Huang, D. H. J. Am. Chem. Soc. 1997, 119, 8105.
3. Yarovenko, V. N.; Shirokov, A. V.; Zavarzin, I. V.; Krupinova, O. N.; Ignatenko, A.
V.; Krayushkin, M. M. Synthesis 2004, 17.
22. Chawalinski, S.; Rypinska, W. Roczniki Chem. 1957, 31, 539. Chem. Abstr. 958, 52,
5284a.
23. Kamai, G. Otdel Khim. Nauk 1952, 923. Chem. Abstr. 1953, 47, 10461a.
24. Ettel, V.; Zbirovsky, M. Chem. Listy 1956, 50, 1265. Chem. Abstr. 1956, 50,
16025h.
1
1
1
4. Ding, Y.; Hu, J. J. Chem. Soc., Perkin Trans. 1 2000, 1651.
5. (a) McCombie, H.; Saunders, B. C.; Stacey, G. J. J. Chem. Soc. 1945, 380; (b)
Hardy, E. E.; Kosolapoff, G. M. U.S. Patent 2,409,039, 1946; Chem. Abstr. 1947,
25. (a) Smith, T. D. J. Chem. Soc. 1962, 1122; (b) Kosolapaff, G. M. In Organic
Phosphorus Compounds; Wiley-Interscience, John Wiley & Sons: New York,
1950; Vol. 6; p 502.
4
1, 1233; (c) Grosse-Ruyken, H.; Uhlig, K. J. Prakt. Chem. 1962, 18, 287; (d)
26. Mark, V. U.S. Patent 1967, 328(3), 472 [Chem. Abstr. 1967, 67, 118098].
27. (a) Goldwhite, M.; Saunders, B. C. J. Chem. Soc. 1955, 3564; (b) Tichy, V.;
Truchlik, S. Chem. Zvesti 1958, 12, 345.
Dennis, E. A.; Westheimer, F. H. J. Am. Chem. Soc. 1966, 88, 3432; (e) Atherton, F.
R.; Bergel, F.; Cohen, A.; Haworth, J. H.; Openshaw, H. T.; Todd, A. R. U.S. Patent
2
,490, 1949; Chem. Abstr. 1950, 44, 3525a; (f) Miyano, M.; Funahashi, S. J. Am.
28. Gutch, P. K.; Srivastava, R. K.; Dubey, D. K. J. Appl. Polym. Sci. 2007, 105,
2203.
29. Vijayraghvan, R.; Kumar, P.; Dubey, D. K.; Singh, R. Biomed. Environ. Sci. 2002,
15, 25.
Chem. Soc. 1955, 7, 3522; (g) Walsh, E. N. J. Am. Chem. Soc. 1959, 81, 3023; (h)
deRose, A. M.; Toet, H. J. Rec. Trav. Chim. 1958, 77, 946; (i) Steinberg, G. M. J. Org.
Chem. 1950, 15, 637; (j) Atherton, F. R.; Openshaw, H. T.; Todd, A. R. J. Chem. Soc.
1
945, 36, 4237.
30. In a typical experimental procedure, dialkylphosphite (0.05 mol) was added to
a suspension of N,N-dichloro poly(styrene-co-divinyl benzene) sulfonamide
polymeric beads (containing 0.05 mol of active chlorine).31 The reaction was
monitored by GC–MS. After complete consumption of the dialkylphosphite, the
mixture was decanted and the pure product was obtained by vacuum
distillation after removing the solvent by distillation.
1
6. (a) Kabachnik, M. I.; Rossiiskaya, M. P. A. Nau. Otdel. Khim. 1958, 1398. Chem.
Abstr. 1959, 53, 6988e; (b) Pudovik, A. N.; Platonova, R. N. Obshch. Khim. 1959,
2
9, 505. Chem. Abstr. 1960, 54, 254f.
7. (a) Fiszer, B.; Michalski, J. Roczniki Chem. 1952, 26, 688. Chem. Abstr. 1955, 49,
306c; (b) Atherton, F. R.; Howard, H. T.; Todd, A. R. J. Chem. Soc. 1948, 1106.
8. Ettel, V.; Zbirovsky, M. Chem. Listy 1956, 50, 1261. Chem. Abstr. 1956, 50,
6025f.
1
1
2
31. Kolthoff, I. M.; Sandell, E. B.; Meehan, E. J.; Bruckenstein, S. Quantitative
Chemical Analysis, 4th ed.; Macmillan: New York, 1969.
1