Trichloroisocyanuric acid: An efficient reagent for the synthesis of dialkyl chlorophosphates from dialkyl phosphites

Article abstract of DOI:10.1016/j.tetlet.2005.06.024

A mild and operationally simple method for the synthesis of dialkyl chlorophosphates is described. Trichloroisocyanuric acid is used as an effective reagent for the rapid conversion of dialkyl phosphites to their corresponding dialkyl chlorophosphates under mild conditions.

Full text of DOI:10.1016/j.tetlet.2005.06.024

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5293–5295
Trichloroisocyanuric acid: an efficient reagent for the synthesis of
dialkyl chlorophosphates from dialkyl phosphites
J. Acharya, A. K. Gupta, P. D. Shakya and M. P. Kaushik*
Process Technology Development Division, Defence R&D Establishment, Jhansi Road, Gwalior 474 002, MP, India
Received 30 April 2005; revised 2 June 2005; accepted 8 June 2005
Abstract—A mild and operationally simple method for the synthesis of dialkyl chlorophosphates is described. Trichloroisocyanuric
acid is used as an effective reagent for the rapid conversion of dialkyl phosphites to their corresponding dialkyl chlorophosphates
under mild conditions.
Ó 2005 Elsevier Ltd. All rights reserved.
Organophosphorus compounds are important both in
living systems and in commercial applications such as
pesticides, fungicides, fire retardants and lubricants.
Dialkyl halophosphates are also important intermedi-
ates for the synthesis of various bioactive compounds
such as phosphoramidates, phosphates, enol phos-
phates and phosphorohydrazides.1–10 Recently, diethyl
chlorophosphate has been used as an efficient reagent
in cyclization reactions8 and in regioselective ring open-
ing of epoxides.9 Because of their wide utility and our
interest in their properties, we intended to reinvestigate
their synthesis. A plethora of effective chemical ap-
proaches have been devised from the corresponding
phosphites (dialkyl phosphates/trialkyl phosphates)
with various reagents such as chlorine,11 phosgene,12
sulfuryl chloride,13 sulfur monochloride and dichlo-
overcome the limitations and drawbacks of the reported
methods.
Herein, we report a rapid, efficient, economic, and easy
to scale-up method for the effective conversion of dialkyl
phosphites to their corresponding dialkyl chlorophos-
phates at room temperature using trichloroisocyanuric
acid as the chlorinating agent. The reagent is less toxic
and within acceptable limits in comparison to that of
other known chlorinating agents and is also an efficient
chlorine releasing agent. This reagent is available com-
mercially and has found infrequent application in syn-
thetic organic chemistry. The developed method has
allowed us to obtain quantitative yields of the products
in reduced reaction times. The room temperature (20–
25 °C) reaction of various dialkyl phosphites with
trichloroisocyanuric acid afforded the corresponding
dialkyl chlorophosphates in 10–15min with excellent
yields (Table 1).20
ride,14,15 CCl4,16 chloramines,17 CuCl2 and N-chloro-
18
succinimide.19 Among these methods, only a few can
be carried out as convenient laboratory methods for
the syntheses of the title compounds. Most of these
reported methods use reagents that are either toxic or
produce undesired by-products, which are difficult to re-
move from the sensitive chlorophosphates.11–16 Another
major drawback of these methods is that they require
harsh reaction conditions, long reaction times10–15 and
also have limited scope in the synthesis of P–N com-
pounds.4d Our aim in undertaking this work was to
The important advantage of this reaction is its occur-
rence at room temperature. Further observation
revealed that reaction completion is indicated by precip-
itation of cyanuric acid, within 10 min, from the homo-
geneous reaction medium. Another advantage is that the
cyanuric acid 4 is formed in quantitative yields and can
be recycled after reaction with elemental chlorine. An-
other positive feature of this reaction is that it requires
only one mole of the reagent 2 to chlorinate three moles
of the phosphites. Furthermore, the reaction does not
require any base to scavenge the proton as it is picked
up by the nitrogen of 2. We also studied the reproduc-
ibility and scale-up feasibility of the developed protocol.
Keywords: Dialkyl phosphite; Dialkyl chlorophosphate; Trichloroiso-
cyanuric acid; Cyanuric acid.
*
Corresponding author. Tel.: +91 751 2343972; fax: +91 751
2341148; e-mail: mpkaushik@rediffmail.com
0040-4039/$ - see front matter Ó 2005Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.024

5294
J. Acharya et al. / Tetrahedron Letters 46 (2005) 5293–5295
Table 1. Preparation of dialkyl chlorophosphates
O
O
O
P
O
Cl
CH3CN
H
O
RO
RO
RO
Cl
H
N
N
N
N
Cl
P
H
RO
r.t., stirring
10-15 min
O
N
Cl
N
H
O
O
4
2
1
3
Entry
R
Yielda (%)
Bp (°C/(mm/Hg))
31P NMRb (ppm)
1
CH3
C2H5
96
98
75–77/20
85–87/10
102–103/10
90–92/10
4.5
6.34
4.14
5.48
2.76
2
3
C3H7
i-C3H7
C4H9
94
98
4
5
95120–122/9
92
8
9
6
i-C4H9
sec-C4H9
C5H11
i-C5H11
C6H13
C6H11
122–124/10
95–97/2
4.16
4.71
7
96
95129–132/1
8
4.5
9
94
96
96
94
96
133–135/1
Undistilled
130–132/1
Undistilled
133–135/0.5
3.58
4.25
5.46
4.7
10
11
11
12
C6H5CH2
C6H5
À6.2
All the products gave satisfactory IR, NMR and GC–MS data.
a Isolated yield of pure products.
b 31P NMR spectra were recorded in CDCl3 using 400 MHz instrument.
4. (a) Di Novi, M.; Trainor, D. A.; Nakanishi, K. Tetra-
hedron Lett. 1983, 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) Froehler, B. C. Tetrahedron Lett. 1986, 27,
5575.
To prove the concept, 1 mol of diethyl phosphite was
treated with 0.33 mol of the reagent 2 to give diethyl
chlorophosphate in excellent yield (90%).
In conclusion we have described an efficient reagent for
the rapid and convenient conversion of dialkyl phosph-
ites to dialkyl chlorophosphates under mild conditions.
Study of a further application of this reagent to detoxify
chemical warfare agents is in progress. Preliminary
experiments have confirmed that the reagent detoxifies
sulfur mustard, a potential chemical warfare agent, com-
pletely, and the by-products produced are under investi-
gation. Details of this study will be reported in due
course.
5. Shi, E.; Pei, C. Synthesis 2004, 2995.
6. (a) Larson, E.; Lining, B. Tetrahedron Lett. 1994, 35, 2737;
(b) Xiao, Q.; Sun, J.; Sun, Q.; Ju, Y.; Zhao, Y-f; Cui, Y-x
Synthesis 2003, 107; (c) Zamyatina, A. Y.; Bushnev, A. S.;
Shvets, V. I. Bioorg. Khim. 1994, 20, 1253.
7. Whitehead, A.; Moore, J. D.; Hanson, P. R. Tetrahedron
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8. Yarovenko, V. N.; Shirokov, A. V.; Zavarzin, I. V.;
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Synthesis 2004, 17.
9. Ding, Y.; Hu, J. J. Chem. Soc., Perkin Trans. 1 2000,
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Acknowledgements
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We thank Shri K. Sekhar, Director, DRDE, Gwalior for
his keen interest and encouragement. The authors would
like to thank Dr. D. K. Dubey for helpful discussions
and Ms. Mamta Sharma for NMR analysis.
References and notes
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20. Typical experimental procedure: To a stirred solution
of trichloroisocyanuric acid, 2 (0.76 g, 3.33 mmol) in
dry acetonitrile (15mL) at room temperature was added
in one portion a solution of diisopropyl phosphite,
(1.66 g, 10 mmol) in acetonitrile (5mL). The result-
ing mixture was stirred at room temperature and
monitored by GC and 31P NMR. After 10 min, cyanuric
acid precipitated indicating completion of the reaction.
It was then further stirred for 5min and filtered to
remove the precipitate followed by removal of solvent
and distillation under vacuum to afford the pure
product.
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