The first isolable dialkyl iodophosphates

Article abstract of DOI:10.1039/b101049m

The synthesis and characterization of the first dialkyl iodophosphates to be isolated in a pure state is described; (CF₃CH₂O)₂P(O)I and [(CF₃)₂CHO]₂P(O)I have electronegative fluoro-ester groups and can be distilled under vacuum.

Full text of DOI:10.1039/b101049m

The first isolable dialkyl iodophosphates
Christopher M. Timperley* and Matthew J. Waters
Defence Science and Technology Laboratory, Chemical and Biological Defence Sector, Porton Down,
Salisbury, Wiltshire, UK SP4 0JQ. E-mail: cmtimperley@dera.gov.uk
Received (in Cambridge, UK) 30th January 2001, Accepted 16th March 2001
First published as an Advance Article on the web 5th April 2001
The synthesis and characterization of the first dialkyl
iodophosphates to be isolated in a pure state is described;
(CF3CH2O)2P(O)I and [(CF3)2CHO]2P(O)I have electroneg-
ative fluoro-ester groups and can be distilled under vac-
uum.
leaving group by protonation, and also because the a-carbon of
the CH3CH2O– group is a softer acid than that of the CF3CH2O–
group, making it more vulnerable to attack by iodide ion, itself
a soft base.
Iodination of bis(hexafluoroisopropyl) phosphite 1b, without
argon blowing through the reaction mixture, gave a 1+2 ratio of
iodophosphate 2b and iodo acid 3 (Scheme 3), as shown by
multinuclear NMR experiments. The iodo acid arises from
dealkylation of the iodophosphate by resident hydrogen iodide;
the by-product (CF3)2CHI was not detected, but most likely
escaped due to its volatile nature.
The study of derivatives of phosphoric acid is one of the oldest
branches of organic chemistry. In 1868, Wichelhaus isolated the
first member of the dialkyl halophosphate series, diethyl
chlorophosphate (CH3CH2O)2P(O)Cl.1 Later work led to the
fluorophosphate (CH3CH2O)2P(O)F2 and the bromophosphate
(CH3CH2O)2P(O)Br; the latter is unstable and decomposes after
3 days at room temperature.3 The corresponding iodophosphate
(CH3CH2O)2P(O)I, like all known iodophosphates, decom-
poses extremely easily and has not been obtained out of
solution.4–6 In continuation of our studies on fluoroalkyl
phosphoryl compounds,7,8 we now describe the synthesis and
characterization of the first isolable dialkyl iodophosphates (and
the first such molecules containing fluoro-ester groups). Our
results indicate that the presence of electronegative fluorine
atoms9 significantly enhances thermal stability.
We prepared bis(fluoroalkyl) phosphites 1a and 1b in good
yield by treating the intermediate from tertiary butanolysis of
phosphorus trichloride, namely Cl2P(O)H, with two molar
equivalents of trifluoroethanol or hexafluoroisopropanol
(Scheme 1).† The synthesis of compound 1a this way was
reported by Gibbs and Larsen; modification of their procedure10
gave the new phosphite 1b. Both bis(fluoroalkyl) phosphites
can be stored in glass vials in a refrigerator for many months
without change.
Scheme 3
Although bis(fluoroalkyl) iodophosphates resist dealkylation
more than their unfluorinated counterparts, hydrogen iodide
formation is best avoided during their synthesis. Treatment of
bis(hexafluoroisopropyl) phosphite 1b with N-iodosuccinimide
(NIS), a convenient source of ‘positive’ iodine, led to good
conversion to the iodophosphate, as shown by GC-MS analysis
of the reaction mixture (Scheme 4). Iodophosphate 2b was
purified by vacuum distillation (bp 46 °C/2 mmHg).§
Scheme 1
Treatment of bis(trifluoroethyl) phosphite 1a with a solution
of iodine in toluene,11 with argon blowing through the mixture
to help remove hydrogen iodide, gave iodophosphate 2a
(Scheme 2). It was purified by vacuum distillation (bp 40 °C/
0.02 mmHg).‡ This is the first time iodination of a dialkyl
phosphite has permitted the isolation of a pure iodophosphate:
the reaction with diethyl phosphite is complicated by deal-
kylation of diethyl iodophosphate by hydrogen iodide, and pure
product cannot be obtained.4 The greater ease of dealkylation of
the CH3CH2O– group compared to the CF3CH2O– group is
because the ethoxy oxygen is more basic than the tri-
fluoroethoxy oxygen, and thus more easily converted into a
Scheme 4
Iodophosphates 2a–b are pale yellow liquids that deposit
traces of black solid on storage in a refrigerator. In line with
other dialkyl halophosphates,1 the iodophosphates might be
expected to be colourless. The yellow colour is probably
attributable to contamination by iodine vapour during distilla-
tion; the deposit during storage is assumed to be precipitated
iodine. The phosphorus chemical shifts in deuteriochloroform
for bis(trifluoroethyl) iodophosphate 2a and bis(hexafluoro-
isopropyl) iodophosphate 2b are 247.7 and 251.3 ppm. Values
for (CH3CH2O)2P(O)I and (CCl3CH2O)2P(O)I in chloroethane
are 241 and 250 ppm respectively.6
In summary, we have developed routes to two dialkyl
iodophosphates that comprise the first such species to have been
isolated and characterized properly. This discovery, which lags
behind the first isolation of a pure dialkyl phosphorochloridate
by over 130 years, opens up new frontiers in organic phosphorus
and iodine chemistry. Further studies relating to the synthesis of
Scheme 2
DOI: 10.1039/b101049m
Chem. Commun., 2001, 797–798
This journal is © The Royal Society of Chemistry 2001
797

1 Refer to G. M. Kosolapoff, Organophosphorus Compounds, John Wiley
& Sons, New York, 1950, p. 242.
a range of bis(fluoroalkyl) phosphites and their reactions with
halogens will be reported in due course.
We thank the Ministry of Defence UK for funding the
work.
2 Diethyl fluorophosphate (CH3CH2O)2P(O)F was first prepared in 1932
by W. Lange and G. von Krüger, Chem. Ber., 1932, 65, 1598. For a
review of the history of this ‘nerve agent’, see C. M. Timperley, Highly
Toxic Fluorine Compounds, in: R. E. Banks (Ed.), Fluorine Chemistry
at the Millennium: Fascinated by Fluorine, Elsevier, Oxford, UK, 2000,
pp. 499–538.
Notes and references
† Materials and methods: trifluoroethanol and hexafluoroisopropanol were
purchased from Apollo Scientific Ltd UK. Analytical information was
obtained using documented instrumentation and techniques: see C. M.
Timperley, M. Bird, I. Holden and R. M. Black, J. Chem. Soc., Perkin
Trans. 1, 2001, 26. NMR data were recorded in CDCl3 solution.
‡ Bis(trifluoroethyl) iodophosphate 2a: a solution of iodine (5.08 g, 0.02
mol) in toluene (100 cm3) was added dropwise to bis(trifluoroethyl)
phosphite (4.92 g, 0.02 mol) in toluene (75 cm3) at 0–5 °C with stirring and
passage of argon through the solution. After addition, the purple solution
was left for 2 h. Residual iodine was removed by filtration through a small
plug of silica gel. Removal of toluene and double distillation of the residue
gave 2a as a pale yellow liquid (3.42 g, 46%). Bp 40 °C/0.02 mmHg. dH
(500 MHz) 4.45 (4H, m, OCH2); dC (125 MHz) 121.4 (dq, J = 13 and 278
Hz, CF3), 69.4 (dq, J = 5 and 37 Hz, OCH2); dF (470 MHz) 274.1 (6F, t,
J = 7 Hz, CF3); nmax/cm21 (film) 1454, 1421, 1296 (PNO), 1174, 1070, 962,
883, 849; m/z (CI) 373 (M + 1), 353 (M 2 F), 245 (M 2 I); HRMS (+ve ion
EI): Calc. for C4H4F6IO3P 371.939 ([M 2 HF]+ = 351.933), found 351.933
(error 0.7).
§ Bis(hexafluoroisopropyl) iodophosphate 2b: a solution of N-iodosuccini-
mide (2.62 g, 11.65 mmol) in acetonitrile (20 cm3) was added dropwise by
cannula to a stirred solution of bis(hexafluoroisopropyl) phosphite (4.45 g,
11.65 mmol) in acetonitrile (30 cm3). After 2 h, GC-MS analysis showed
good conversion to product. Removal of solvent and double distillation of
the oily residue gave 2b as a pale yellow liquid (3 g, 51%). Bp 46 °C/2
mmHg. dH (500 MHz) 5.28 (2H, dsep, J = 5 Hz, OCH); dC (125 MHz)
119.9 (dq, J = 6 and 282 Hz, CF3), 71.9 (dsep, J = 7 and 37 Hz, OCH); dF
(470 MHz) 272.3 (6F, m, CF3), 273.2 (6F, m, CF3); nmax/cm21 (film)
1379, 1300 (PNO), 1280–1205 (strong bands), 1117, 1068, 904, 879, 854;
m/z (CI) 509 (M + 1), 489 (M 2 F), 381 (M 2 I); HRMS (+ve ion EI): Calc.
for C6H2F12IO3P 507.933 ([M 2 HF]+ = 487.927), found 487.926 (error
1.6).
3 H. Goldwhite and B. C. Saunders, J. Chem. Soc., 1955, 3564.
4 H. McCombie, B. C. Saunders and G. J. Stacey, J. Chem. Soc., 1945,
921.
5 A. Skowronska, M. Pakulski, J. Michalski, D. Cooper and S. Trippett,
Tetrahedron Lett., 1980, 21, 321.
6 Although the synthesis of (CH3CH2O)2P(O)I and the chloro analogue
(CCl3CH2O)2P(O)I have been prepared by iodination of the respective
trialkyl phosphites at 240 °C, their purification and full characterization
has not been carried out. See J. Michalski, M. Pakulski and A.
Skowronska, J. Chem. Soc., Perkin Trans. 1, 1980, 833.
7 C. M. Timperley, J. F. Broderick, I. Holden, I. J. Morton and M. J.
Waters, J. Fluorine Chem., 2000, 106, 43.
8 C. M. Timperley, I. Holden, I. J. Morton and M. J. Waters, J. Fluorine
Chem., 2000, 106, 153.
9 The hexafluoroisopropoxy group is more electron-withdrawing than the
trifluoroethoxy group: pKa values for (CF3)2CHOH and CF3CH2OH are
9.3 and 12.4 respectively (compare these with 17.1 for isopropanol and
15.9 for ethanol). See M. Hudlicky, Chemistry of Organic Fluorine
Compounds, Ellis Horwood, London, 2nd Edition, 1992, p. 550.
10 D. E. Gibbs and C. Larsen, Synthesis, 1984, 410. The reaction mixture
from tertiary butanolysis of phosphorus trichloride was left for 1 h at
0–5 °C and hexafluoroisopropanol was added dropwise over 30 mins.
After standing for 12 h at rt, the mixture was heated under reflux for 3
h, the solvent removed and the residue distilled to give bis(hexa-
fluoroisopropyl) phosphite 1b as a mobile colourless liquid (71%). Bp
62 °C/8 mmHg.
11 The solubility of iodine in g kg21 of solvent at 25 °C decreases in the
order: toluene 1875 > diethyl ether 337 > benzene 164; see Kirk-
Othmer Encyclopedia of Chemical Technology, Wiley, New York, 3rd
Edition, 1978, vol. 13, p. 652. Toluene is therefore the best choice of
solvent for the iodination reaction.
798
Chem. Commun., 2001, 797–798