Trichloroisocyanuric acid-KF as an efficient reagent for one-pot synthesis of dialkylfluorophosphates from dialkylphosphites

Article abstract of DOI:10.1080/00397910802215880

Trichloroisocyanuric acid-KF afforded dialkylfluorophosphates from dialkylphosphites at room temperature through a facile electrophilic- nucleophilic metathesis. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802215880

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Trichloroisocyanuric Acid–KF
as an Efficient Reagent
for One-Pot Synthesis of
Dialkylfluorophosphates from
Dialkylphosphites
J. Acharya a , A. K. Gupta a , Deepak Pardasani a , D.
K. Dubey a & M. P. Kaushik a
a Process Technology Development Division, Defence
Research and Development Establishment , Gwalior,
India
Published online: 14 Oct 2008.
To cite this article: J. Acharya , A. K. Gupta , Deepak Pardasani , D. K. Dubey
& M. P. Kaushik (2008) Trichloroisocyanuric Acid–KF as an Efficient Reagent for
One-Pot Synthesis of Dialkylfluorophosphates from Dialkylphosphites, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 38:21, 3760-3765, DOI: 10.1080/00397910802215880
To link to this article: http://dx.doi.org/10.1080/00397910802215880
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Synthetic Communications1, 38: 3760–3765, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802215880
Trichloroisocyanuric Acid–KF as an Efficient
Reagent for One-Pot Synthesis of
Dialkylfluorophosphates from Dialkylphosphites
J. Acharya, A. K. Gupta, Deepak Pardasani, D. K. Dubey,
and M. P. Kaushik
Process Technology Development Division, Defence Research and
Development Establishment, Gwalior, India
Abstract: Trichloroisocyanuric acid–KF afforded dialkylfluorophosphates from
dialkylphosphites at room temperature through a facile electrophilic–nucleophilic
metathesis.
Keywords: Dialkylfluorophosphate, dialkylphosphite, KF, trichloroisocyanuric acid
Because of the wide utility of OPFCs and our interest in exploring the
effective medicinal and protective countermeasures against such fluori-
dates, there is a need to develop a rapid and efficient synthetic procedure
for these compounds. Several methods have been reported in the litera-
ture involving mainly two types of reactions: first, based on halogen
metathesis, in which dialkyl chlorophosphates are reacted with metal
fluorides in the presence of crown ethers. Chlorine exchange is also
reported using sodium tetrafluoroborate, sodium hexafluoro silicate, or
hexa flurophosphate.[1,2] The second approach is based on the replace-
ment of active hydrogen of dialkyl phosphite either with alkali metals
or with trimethyl silylchloride, followed by reaction with an activated
source of fluorine atom.[3] The first protocol has drawbacks such as
use of an expensive reagent such as crown ethers, excess reagent, high
Received March 18, 2008.
Address correspondence to M. P. Kaushik, Process Technology Development
Division, Defence Research and Development Establishment, Jhansi Road,
Gwalior 474002, MP, India. E-mail: mpkaushik@rediffmail.com
3760

Trichloroisocyanuric Acid–KF
3761
temperature (200 ꢀC), and variable yield (12–77%). In the second method,
dialkylphosphites were converted to their alkali metal salts followed by
reaction with sulfuryl chloride fluoride.[3] Though this method apparently
looks better, it gives a mixture of chloridates and fluoridates, and isola-
tion of pure fluoridates becomes very difficult. Another major drawback
of these methods is that they require reaction conditions that are difficult
to maintain, such as temperature of ꢁ50 ꢀC. In addition, these reactions
make use of dialkyl chlorophosphates as starting materials, which in turn
need to be prepared from dialkyl phosphites. Recently, the use of solid-
supported ion exchange resin Amberlyst A-26 with a fluoride counterion
in tetrahydrofuran (THF) at room temperature under an argon atmo-
sphere is also reported.[4] However, the ion exchange resin Amberlyst
A-26 with a fluoride counter ion is a costly affair and ion exchange reac-
tions are reversible; thus formation of products always depends on the
concentration of fluoride ions, in ion exchange resin. Furthermore, this
process is time consuming; up-scaling is difficult and needs to be done
in the argon atmosphere. These limitations prompted us to develop a
rapid and efficient synthetic procedure for dialkyl fluorophosphates that
involves easy workup and quantitative yields in shorter reaction times by
making use of a trichloroisocyanuric acid (TCICA)–KF mixture.
RESULTS AND DISCUSSION
TCICA is a stable, commercially available crystalline compound that
provides three active chlorines.[5] We envisaged that if TCICA–KF is
used in combination to react with dialkylphosphites, it would generate
corresponding dialkyl flurophosphates via the intermediacy of dialkyl
chlorophsphates. To the best of our knowledge, TCICA–KF has not
been used so far as a fluorinating agent in organic synthesis. In continua-
tion of our recent efforts to develop new reagents and synthetic proce-
dures for the rapid synthesis of organophosphorus compounds,[6]
herein, we report a rapid, efficient, economic, and easy-to-scale method
for the effective conversion of dialkylphosphites to their corresponding
dialkyl fluorophosphates at room temperature. Reaction of diisopropyl-
phosphite (1.66 g, 10 mmol) with TCICA (0.76 g, 3.3 mmol) and KF
(0.64 g, 11 mmol) was performed at room temperature, and an exother-
mic reaction was observed, which was monitored by 31P NMR. To our
surprise, a quantitative conversion of diisopropyl phosphite to diisopro-
pyl fluorophosphate was observed within 25 min. It led us to further
explore the generality of this reaction with structurally diverse dialkyl
phosphites. The reaction of various dialkyl phosphites with

3762
J. Acharya et al.
Scheme 1. Synthesis of dialkylfluorophosphate.
TCICA–KF afforded corresponding dialkyl fluorophosphates in 20–
45 min with excellent yields. The reaction scheme and yields of dialkyl
fluorophosphates are depicted in Scheme 1 and Table 1.
This method has allowed us to obtain the quantitative yields of the
products in reduced reaction times. The important advantage of this reac-
tion is the occurrence of the reaction at room temperature, and comple-
tion of the reaction is indicated by the precipitation of cyanuric acid and
KCl within 20–45 min. It was also observed that reaction time increases
with increasing the alkyl chain of the substituents. It is probably due to
the participation of p-electrons present on the phosphorus atom, which
Table 1. Preparation of dialkylfluorophosphates from dialkyl phosphites using
TCICA and KF in acetonitrile at room temperature
Time Yielda
31P–NMRb
(ppm)
Entry
R
(min)
(%)
Bp ꢀC (mm=Hg)
JP–F (Hz)
1
2
3
4
5
6
7
8
9
CH3
C2H5
C3H7
20
20
25
20
30
30
30
35
30
35
45
90
89
90
94
91
92
95
91
89
93
94
65–67=25
75–77=20
76–77=15
80–82=20
85–87=12
110–112=15
95–97=5
141–142=35
142–143=25
120–121=1.2
116–117=1.0
ꢁ8.39
ꢁ8.22
ꢁ8.48
ꢁ10.25
ꢁ9.25
ꢁ10.31
ꢁ10.71
ꢁ9.49
ꢁ8.99
ꢁ8.98
ꢁ20.25
975.10
970.25
958.14
968.40
971.39
968.00
972.00
962.25
967.00
966.74
990.10
iC3H7
nC4H9
iC4H9
Sec-C4H9
C5H11
iC5H11
C6H11
C6H5
10
11
aisolated yield.
b31P NMR spectra were recorded at 162 MHz in CDCl3. All the products gave satisfactory
IR, NMR, and GC-MS data compared with authentic samples.
Note. Caution! Dialkylfluorophosphates are highly toxic compounds and should be
synthesized by trained persons using an efficient fume hood. Great caution should be exer-
cised especially while distilling them, and residue must be properly decontaminated by using
20% alkali solution.

Trichloroisocyanuric Acid–KF
3763
might have reduced the electrophilic character of the phosphorus atom.
The formation of cyanuric acid from a heterogeneous reaction medium
was confirmed after dissolving the precipitate in acetone followed by fil-
tration to remove undissolved KCl. The by-product (cyanuric acid and
KCl) can be removed just by filtration of reaction mixture using suction.
Further, to study the up-scaling of such compounds, we carried out a
reaction of diisopropylphosphite (1.0 mol) with TCICA (0.34 mol) and
KF (1.1 mol), which also gave diisopropyl fluorophosphates with 94%
yield. It was also observed that when in situ–generated diisopropylchlor-
ophosphate was isolated and fluorine exchange reaction was performed
by the use of KF (1:2), the reaction took 90 min and that under reflux
conditions yield is also reduced (74%).
CONCLUSIONS
In conclusion, we have reported an efficient, convenient, and one-pot
conversion of dialkylphosphites to dialkylfluorophosphates under mild
conditions and in excellent yields.
EXPERIMENTAL
Chemicals purchased from Acros, Sigma-Aldrich, and Merck (India)
were used without further purification, and solvents were distilled prior
1
to use. H NMR spectra were recorded on a Bruker Avance 400 (400-
MHz) spectrometer (chemical shifts in d, ppm) against TMS as internal
standard and IR spectra were recorded as KBr pellets on a Bruker model
Tensor 27 FTIR spectrophotometer (n, cmꢁ1).
Typical Experimental Procedure
Diisopropylphosphite, 16.6 g (0.10 mol), was added to a stirred suspen-
sion of trichlorocyanuric acid (7.6 g, 0.0333 mol) and KF (6.38 g,
0.11 mol) in dry acetonitrile (40 ml) at room temperature in one shot.
The resulting mixture was stirred at room temperature, and an exother-
mic reaction took place, which was periodically monitored by GC and
31P NMR. It was then further stirred for 5 min and filtered off to remove
the precipitate by suction. The solid precipitate was washed with
2 ꢂ 10 mL of ether. The filtrate and washings were combined. The solvent
was removed under vacuum, and product was obtained by distillation
under vacuum. Bp 80–82=20 Hg; yield; 17.32 g. (94%).

3764
J. Acharya et al.
ACKNOWLEDGMENT
We thank Dr. R. Vijayaraghavan, director, DRDE, Gwalior, for his keen
interest and encouragement.
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