Journal of Fluorine Chemistry 106 (2000) 153±161

Fluorinated phosphorus compounds

Part 3. The synthesis of symmetrical and unsymmetrical
¯uoroalkyl phosphates
Christopher M. Timperley*, Ian Holden, Ian J. Morton, Matthew J. Waters
Chemical and Biological Defence Sector, Defence Evaluation and Research Agency, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK
Received 19 June 2000; accepted 9 July 2000

Abstract

Treatment of phosphorus pentachloride with four molar equivalents of ¯uoroalcohol gave symmetrical phosphates (RFO)3PˆO in
isolated yields between 10±92% [RF ˆCF3CH2, C2F5CH2, HCF2CF2CH2, C3F7CH2, (FCH2)2CH, (CF3)2CH, C2F5(CH3)CH]. The reaction
proceeded best for ¯uoroalcohols having many ¯uorine atoms. 2,2-Di¯uoroethanol HCF2CH2OH and 1,3-di¯uoroisopropanol
(FCH2)2CHOH did not react cleanly and gave product mixtures. Hexa¯uoroisopropanol produced a 3:7 mixture of symmetrical phosphate
[(CF3)2CHO]3PˆO and chlorophosphorane [(CF3)2CHO]4PCl. The latter reacted readily with water and alcohols. Heating the chloridates
CF3CH2OP(O)Cl2, (CF3CH2O)2P(O)Cl and (C2F5CH2O)2P(O)Cl with various ¯uoroalcohols in the presence of calcium chloride catalyst
gave unsymmetrical phosphates in isolated yields between 46±83%. The mixed phosphate (CF3CH2O)2P(O)OCH2C2F5 did not react with
butanol or propylamine in dichloromethane at room temperature. # 2000 Elsevier Science S.A. All rights reserved.

Keywords: Bis(¯uoroalkyl)phosphorochloridate; Bis(¯uoroalkyl)¯uoroalkyl phosphate; Fluorinated phosphate; Tetra(hexa¯uoroisopropoxy)chloropho-

sphorane; Tris(¯uoroalkyl)phosphate

1. Introduction

The lowest members of the symmetrical ¯uoroalkyl

phosphate family were ®rst made in the ®rst half of the
last century by two master ¯uorine chemists: tris(2-¯uoro-
ethyl) phosphate 1 by Knunyants et al. [1] and tris(2,2-
di¯uoroethyl) phosphate 2 by Swarts [2].1 The phosphates
were prepared by the ¯uoroalcoholysis of phosphorus oxy-
chloride (route A) or phosphorus pentabromide (route B).
The ®rst reaction requires a base and an inert solvent, Modi®cation of routes A and B has provided other
whereas the second is conducted without solvent. Phosphate symmetrical ¯uoroalkyl phosphates, including the third
2 has also been made by oxidation of tris(2,2-di¯uoroethyl)- ethyl analogue, tris(2,2,2-tri¯uoroethyl) phosphate (CF3-
phosphite (HCF2CH2O)3P with oxygen in the presence of CH2O)3PˆO [4±7]. Other homologues include
chloral [3]. (C2F5CH2O)3PˆO [6,7], (C3F7CH2O)3PˆO [5±10] and
[(CF3)2CHO]3PˆO [11]. Fluoroalkyl phosphates with more
remote ¯uorine atoms have received little attention,
although (CF3CH2CH2O)3PˆO has been made [6,7].
*
Corresponding author. Tel.: ‡44-1980-613566; Some related phosphates have the general formula
fax: ‡44-1980-613371. [H(CF2)nCH2O]3PˆO. Members with an even number of
1
Organic phosphorus compounds are named after the corresponding di¯uoromethylene groups (n ˆ 2, 4, 6 or 8) have been
parent acids. Most of the substances described in this paper are derivatives prepared by route A [12,13] or route B [5], by ¯uoro-
of phosphoric acid (HO)3P=O. Compounds of structure (RFO)3P=O are
symmetrical phosphates or tris(fluoroalkyl) phosphates, while those of
alcoholysis of phosphorus pentoxide [14], by dinitrogen
structure (RFO)2P(O)ORF0 are unsymmetrical phosphates or bis(fluoro- tetraoxide oxidation of tris(¯uoroalkyl) phosphites [15],
alkyl) fluoroalkyl phosphates. or by pyrolysis of bis(¯uoroalkyl) phosphoric acids [15].

0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 0 ) 0 0 3 2 7 - 4
154 C.M. Timperley et al. / Journal of Fluorine Chemistry 106 (2000) 153±161

Surprisingly few unsymmetrical tris(¯uoroalkyl) phosphates Table 1

have been reported; the molecule (CF3CH2O)2P(O)OC- Experimental data for symmetrical phosphates (RFO)3P=O
(Me)2(CF2)4H is a rare example [16]. Compound RF Yield (%) Bp (8C/mmHg)
Previous work from this laboratory described the pre-
7 CF3CH2 73 40/0.6a
paration of dialkyl ¯uoroalkyl phosphates (RO)2P(O)ORF 8 C2F5CH2 69 64/0.9b
[17] and bis(¯uoroalkyl) alkyl phosphates (RFO)2P(O)OR 9 H(CF2)2CH2 66 102/0.015c
[18]. This paper addresses the synthesis of some symme- 10 C3F7CH2 76 63/0.08d
trical and unsymmetrical tris(¯uoroalkyl) phosphates. Sym- 11 (FCH2)2CH 10 49/0.02
12a (CF3)2CH 92 mp 248Ce
metrical phosphates were made by the direct interaction of
18 C2F5(CH3)CH 21 62/0.8
phosphorus pentachloride with four molar equivalents of a
¯uoroalcohol. The use of linear and branched ¯uoroalcohols 74±758C/9 mmHg [4], 186±1898C [5] and 738C/8 mmHg [6,7].
b
678C/1.5 mmHg [6,7].
permitted the mechanism of reaction to be deduced. c
250±2558C [5], 1218C/2 mmHg [13] and 1158C/1 mmHg [14].
d
220±2238C [5], 968C/2.5 mmHg [6,7] and 78±808C/0.5 mmHg [10].
e
This compound has also been prepared by treatment of phosphorus
oxychloride with three molar equivalents of (CF3)2CHOLi in ether (90%
yield and mp 238C) [11].

Unsymmetrical phosphates were prepared by heating

phosphorochloridates 3±5 with ¯uoroalcohols in the pre-
sence of calcium chloride. electron-acceptor groups on phosphorus stabilise the ®ve
coordinate state [20]; e.g. penta(tri¯uoroethoxy)phosphor-
ane (CF3CH2O)5P can be distilled without decomposition
2. Results and discussion [21].
Primary ¯uoroalcohols containing three or more ¯uorine
2.1. Synthesis of tris(fluoroalkyl) phosphates atoms reacted rapidly with phosphorus pentachloride to
afford phosphates 7±10 in good yield (Table 1).
The reaction of phosphorus pentabromide [2] or pen-
tachloride [5] with four moles of ¯uoroalcohol generates
one mole of tris(tri¯uoroalkyl) phosphate, one mole of
¯uoroalkyl halide, and four moles of hydrogen halide (refer
to route B in the Section 1). Chuganov and Sapgir [5]
reported the reactions of phosphorus pentachloride with
primary ¯uoroalcohols, but experimental details and spec-
The secondary ¯uoroalcohol, 1,3-di¯uoroisopropanol,
troscopic data for the products were not recorded. Their
gave a mixture of products identi®able by GC±MS, which
postulated mechanism involved instant generation of POCl3
(via elimination of ¯uoroalkyl halide from the phosphorane included mono- and bis-¯uoroalkyl phosphorochloridates
(FCH2)2CHOP(O)Cl2 and [(FCH2)2CHO]2P(O)Cl. Symme-
RFCH2OPCl4) and its subsequent reaction with three mole-
trical phosphate 11 was separated by fractionation. The low
cules of ¯uoroalcohol. However, phosphorus oxychloride is
yield, like that found with 2,2-di¯uoroethanol, shows that
normally unreactive towards ¯uoroalcohols under neutral or
sparsely ¯uorinated alcohols cannot form phosphates as
acidic conditions [8,18]. Our studies were directed at solving
easily as highly ¯uorinated ones (perhaps as a consequence
this apparent contradiction.
of the lower stabilities of the phosphorane intermediates).
The reaction of 2-¯uoroethanol with phosphorus pen-
tachloride was not pursued owing to the high toxicity of
the alcohol [19]. The next homologue, 2,2-di¯uoroethanol,
yielded a mixture of tris(di¯uoroethyl) phosphate 2, phos-
phorochloridates 6a and 6b, and phosphorus oxychloride. The reaction of hexa¯uoroisopropanol with phosphorus
pentachloride followed an unexpected course and
furnished two products: desired phosphate 12a and stable
intermediate 12b in a 3:7 ratio. The composition of the
mixture remained constant for repeat experiments and could
not be altered by fractionation as both products co-distilled.
The origin of the phosphate is not obvious; it did not
The individual yields parallel the stabilities of the phos- originate from phosphorane hydrolysis as anhydrous con-
phorane intermediates and their ease of elimination of ditions were used.
2-chloro-1,1-di¯uoroethane. The stabilities decrease in the
order (HCF2CH2O)4PCl > …HCF2CH2O)3PCl2 > …HCF2-
CH2O)2PCl3 > HCF2CH2OPCl4. It is recognised that
 C.M. Timperley et al. / Journal of Fluorine Chemistry 106 (2000) 153±161 155

Tetra(hexa¯uoroisopropoxy)chlorophosphorane 12b is a
missing link in the hexa¯uoroisopropoxy-phosphorane
family: the related entities [(CF3)2CHO]3PCl2 and
[(CF3)2CHO]5P have already been isolated [11]. Like these,
the former is covalent, and is expected to have a trigonal
bipyramidal structure. The phosphorus chemical shift of
chlorophosphorane 12b is d 67 ppm, i.e. in the region typical
of covalent phosphoranes. It did not give a molecular ion in
the high-resolution mass spectrum, but ions of m/z 715 and
m/z 699 were prominent, corresponding respectively to loss
of F and Cl from the molecule. The high stability of 12b
compared to analogues derived from primary ¯uoroalcohols,
e.g. (C2F5CH2O)4PCl, is due to the greater electron-with-
drawing ability of the hexa¯uoroisopropoxy group and its
greater bulk which disfavours the Arbusov rearrangement:

Tetra(hexa¯uoroisopropoxy)chlorophosphorane 12b is
sensitive to moisture. Addition of water to the 3:7 phos-
phate±phosphorane mixture resulted in rapid hydrolysis of
the phosphorane, allowing the isolation of pure tris(hexa-
¯uoroisopropyl) phosphate 12a. Alternative routes to this
compound involve hydrolysis of the phosphoranes
[(CF3)2CHO]3PCl2 and [(CF3)2CHO]5P [11].

Methanolysis of 12b resulted in substitution of the chlor-

ine atom, probably via an octahedral intermediate [21], to
give 50% methoxyphosphorane 13 (Fig. 1). Further reaction
gave the unstable dimethoxyphosphorane 14 which col-
lapsed by two pathways to give 12% bis(hexa¯uoroisopro- Fig. 1. The methanolysis of tetra(hexafluoroisopropoxy)chlorophosphor-
pyl) methyl phosphate 15 (via loss of hexa¯uoroisopropyl ane.
methyl ether) and 6% dimethyl hexa¯uoroisopropyl phos-
phate 16 (via loss of bis(hexa¯uoroisopropyl)ether).
Unstable dimethoxyphosphorane 14 also underwent metha- rapidly with alcohols to afford tri¯uoroethyl ethers [22]. The
possibility that phosphates 15 and 16 might arise from
nolysis to trimethoxyphosphorane 17 which collapsed, pre-
transesteri®cation of the tris(hexa¯uoroisopropyl) phos-
sumably by loss of bis(hexa¯uoroisopropyl)ether, to give a
phate in the starting mixture was excluded as its proportion
trace of trimethyl phosphate.
remained constant before and after the reaction. Tris(¯uoro-
The products were identi®ed by analysis by NMR and
GC±MS, a standard of compound 15 existing from current alkyl) phosphates are also unreactive towards alcohols such
work2 and one of compound 16 existing from previous work as butanol (see Section 2.3).
[17]; trimethyl phosphate is available commercially. Meth- The multiple reaction pathways clearly show the desta-
oxyphosphorane 13, like other ¯uoroalkoxy-substituted bilising effect of increased alkoxy substitution on penta-
coordinate phosphorus. Interestingly, phosphorane 14
phosphoranes [11], did not give a molecular ion in its mass
bearing hexa¯uoroisopropyl and methoxy groups eliminated
spectrum, but gave a minor peak at m/z 699 (loss of a
a larger proportion of the unsymmetrical methoxy ether
methoxy group) and a major peak at m/z 563 (loss of a
(CF3)2CHOMe compared to the symmetrical ¯uoroether
hexa¯uoroisopropoxy group). Its phosphorus chemical shift
is d-83 ppm. The formation of ¯uoroethers as by-products is (CF3)2CHOCH(CF3)2; ejection of dimethyl ether was not
assumed. It is however known that Ph3P(OCH2CF3)2 reacts apparent (see Fig. 1).
The reaction of racemic 3,3,4,4,4-penta¯uoro-2-butanol
2 with phosphorus pentachloride did not provide a stable
The synthesis of pure bis(hexafluoroisopropyl) phosphorochloridate
[(CF3)2CHO]2P(O)Cl, a potent electrophile, and its reaction with methanol
phosphorane, but instead gave the symmetrical phosphate
and triethylamine in ether to furnish phosphate 15 will be discussed in a 18 in poor yield. This phosphate contains three chiral ester
later paper. groups. A pair of diastereoisomers form, one when the three
 156
Table 2

C.M. Timperley et al. / Journal of Fluorine Chemistry 106 (2000) 153±161

Spectroscopic data for symmetrical tris(fluoroalkyl) phosphates (RFO)3P=O (NMR data measured in CDCl3)

Compound 1
H NMR d, J (Hz) 13
C NMR d, J (Hz) 19
F NMR d, J (Hz) 31
P NMR d IR n (cmÿ1) HRMS analysis

7 4.43 (6H, dq, J ˆ 8, 12, OCH2) 122 (dq, J ˆ 9, 276, CF3), ÿ74.5 (9F, t, J ˆ 7, CF3) ÿ3.7 1460, 1425, 1288 (P=O), 1178, Calculated C6H6F9O4P 343.986,
64.3 (dq, J ˆ 4, 40, OCH2) 1084, 964, 899, 845 found 343.985 (error 3.4 ppm)
8 4.5 (6H, dt, J ˆ 8, 12, OCH2) 118.2 (tq, J ˆ 35, 285, CF3), ÿ124.5 (6F, t, J ˆ 12, CF2), ÿ4.0 1356, 1308 (P=O), 1205, 1163, Calculated C9H6F15O4P 493.976,
111.2 (dtq, J ˆ 10, 257, 36, ÿ83.2 (9F, m, J ˆ 12, CF3) 1113, 1068, 1032, 937, 897 found 493.975 (error 2.4 ppm)
CF2), 63.5 (dt, J ˆ 4, 28, OCH2)
9 5.92 (3H, tt, J ˆ 3, 43, CF2H), 113.3 (dtt, J ˆ 9, 30, 250, CF2), ÿ136.5 (6F, d, J ˆ 43, CF2H), ÿ3.5 1460, 1404, 1294 (P=O), 1240, Calculated C9H9F12O4P 440.005,
4.46 (6H, dt, J ˆ 5, 13, OCH2) 107 (tt, J ˆ 37, 287, CF2H), ÿ123.7 (6F, dt, J ˆ 3, 13, CF2) 1215, 1109, 1070, 951, 899, 835 found 439.999 (error 12.7 ppm)
63.6 (dt, J ˆ 6, 31, OCH2)
10 4.55 (6H, dt, J ˆ 8, 12, OCH2) 117.2 (tq, J ˆ 34, 287, CF3), ÿ127.3 (6F, m, CH2CF2), ÿ3.4 1460, 1410, 1356, 1301 (P=O), Calculated C12H6F21O4P
113.1 (ttd, J ˆ 258, 31, ÿ121.5 (6F, m, CF2CF3), 1232, 1186, 1126, 1086, 1016, 643.967, found 643.966
9, OCH2CF2), 108.4a ÿ80.7 (9F, m, CF3) 931 (error 0.7 ppm)
(t, J ˆ 265, CF2CF3),
63.7 (td, J ˆ 25, 3, OCH2)
11 5.1 (3H, complex m, OCH), 80 (ddd, J ˆ 174, 7, 7, CH2F), ÿ46.3 (6F, dt, J ˆ 18, 47, 8.6 1460, 1412, 1290 (P=O), 1088, Calculated C9H15F6O4P 332.061
4.6 and 4.8 (12H, complex m, 78.6 (dt, J ˆ 9, 21, OCH) CH2F) 1051, 999, 908 ([M±CH2FŠ‡ ˆ 299:047),
CH2F)b found 299.046 (error 4.7)
12a 5.1 (3H, br m, OCH) 119.7 (dq, J ˆ 10, 282, CF3), ÿ73.3 (18F, d, J ˆ 5, CF3) ÿ3.6 1379, 1355, 1290 (P=O), 1237, Calculated C9H3F18O4P 547.948,
74.4 (dsep, J ˆ 14, 35, OCH) 1115, 909, 881, 819 found 547.948 (error ÿ0.5 ppm)
18 4.87 (3H, m, OCH), 118 (tq, J ˆ 38, 285, CF3), Very complex due to the ÿ6.2 and ÿ4.7 1458, 1394, 1327, 1288 (P=O), Calculated C12H12F15O4P
1.55 (9H, br m, CH3) 112 (m, CF2), 72 (br t, OCH), existence of two 1253, 1203, 1159, 1130, 1080, 536.023, found 536.017
14.3 (s, CH3) diastereoisomers 1045, 991, 968, 843 (error 11 ppm)
a
Complicated by two sets of 2 JCÿF .
b
The proton spectrum is second order and is very complex (perhaps an AA0 BB0 CMX system; this would need a computer simulation to resolve and is not amenable to first order analysis).
 C.M. Timperley et al. / Journal of Fluorine Chemistry 106 (2000) 153±161 157

ester groups are of equal con®guration (i.e. RRR or SSS Ð Bis(¯uoroethyl)phosphorodichloridate 4 also combined
two possibilities), and the other when they are of mixed with primary ¯uoroalcohols to give unsymmetrical phos-
con®guration (i.e. RSS, SSR, RSR, SRS, SRR, RRS Ð six phates 24±26 in reasonable yield (Table 3). The reaction
possibilities). The expected 1:3 mixture was observed by with penta¯uoropropanol was scaled up to provide over 50 g
phosphorus NMR spectroscopy (see Table 2). of pure bis(tri¯uoroethyl) penta¯uoropropyl phosphate 24
(see Section 4.8)

Tertiary ¯uoroalcohols did not combine with phosphorus

pentachloride; CF3(CH3)2COH, CH3(CF3)2COH and
(CF3)3COH remained unchanged. The cyclic ¯uoroalcohols,
2,2,3,3-tetra¯uorocyclobutanol 19 and (per¯uorocyclohex-
yl)methanol 20, gave complex mixtures; no attempt Similarly, bis(penta¯uoropropyl)phosphorochloridate 5
was made to purify and characterise the individual compo- combined with tetra¯uoropropanol and hepta¯uorobutanol
nents. to afford phosphates 27 and 28 in good yields.

The symmetrical ¯uoroalkyl phosphates that were iso-

lated were colourless stable liquids. Their yields and boiling
Like the symmetrical phosphates, the unsymmetrical
points are given in Table 1 and spectroscopic data in Table 2.
¯uoroalkyl phosphates were isolated as colourless stable
liquids. Their yields and boiling points are given in Table 3
2.2. Synthesis of bis(fluoroalkyl) fluoroalkyl phosphates
and spectroscopic data in Table 4.
The reaction of ¯uorinated alcohols with phosphoryl
2.3. The reactivity of bis(trifluoroethyl) pentafluoropropyl
chlorides generally takes place in the presence of base
phosphate to nucleophiles
[8,18] but not under neutral or acidic conditions. One
way of facilitating nucleophilic attack is to use a Lewis
To end speculation concerning the potential reactivity of
acid which increases the positive charge on phosphorus by
the mixed phosphates to nucleophiles, compound 24 was
coordination to the oxygen atom of the P=O group [16].
treated in separate experiments with molar equivalents of
Un¯uorinated phosphorus ester groups often undergo clea-
butanol and propylamine. In both cases, no products were
vage of the carbon±oxygen bond under these conditions due
detected by GC±MS analyses and the starting phosphate was
to release of hydrogen chloride. However, as shown in the
recovered unchanged (see Section 4.9).
¯uoroalcoholysis of phosphorus pentachloride, ¯uorinated
phosphorus ester groups are not cleaved by hydrogen chlor-
ide even on prolonged heating. This has enabled the synth-
esis of many symmetrical phosphates having ¯uoro aliphatic
[7,10,16,23,24] and aromatic [16,25±32] substituents, with
Group I±III metal salts being used as catalysts. In the present
study, some ¯uoroalkyl-substituted phosphoryl chlorides
Table 3
were found to react with several aliphatic ¯uoroalcohols
Experimental data for unsymmetrical phosphates
in the presence of 5% calcium chloride catalyst to afford
unsymmetrical ¯uoroalkyl phosphates. Compound RF RF0 Yield (%) Bp (8C/mmHg)
Tri¯uoroethyl phosphorodichloridate 3 combined with Products of general formula RFCH2OP(O)(OCH2RF0 )2
primary ¯uoroalcohols to give phosphates 21±23 in mod- 21 CF3 C2F5 69 100/10
erate yield (Table 3). The secondary ¯uoroalcohol 22 CF3 (CF2)2H 58 124/5
(CF3)2CHOH, or the tertiary ¯uoroalcohols CF3(CH3)2COH 23 CF3 C3F7 65 100/1
and CH3(CF3)2COH, did not react. Products of general formula (RFCH2O)2P(O)OCH2RF0
24 CF3 C2F5 68a 82/10
25 CF3 (CF2)2H 46 100/10
26 CF3 C3F7 55 85/10
27 C2F5 (CF2)2H 83 94/5
28 C2F5 C3F7 80 104/10
a
In the scale-up reaction, an improved yield of 77% was achieved, the
boiling point being 738C/5 mmHg (see Section 4.8).
 158
Table 4
Spectroscopic data for unsymmetrical phosphates RFCH2OP(O)(OCH2RF0 )2 and (RFCH2O)2P(O)OCH2RF0 (NMR data measured in CDCl3)

Compound 1
H NMR d, J (Hz) 13
C NMR d, J (Hz)a 19
F NMR d, J (Hz) 31
P NMR d IR n (cmÿ1) HRMS analysis

21 4.51 (4H, dt, J ˆ 4, 122 (tq, J ˆ 34, 286, CF2CF3), ÿ124.5 (4F, t, J ˆ 13, ÿ3.9 1460, 1356, 1308, 1282 (P=O), Calculated C8H6F13O4P 443.980,
12, OCH2C2F5), 121.9 (dq, J ˆ 13, 286, CF3), CF2), ÿ83.2 (6F, br m, 1207, 1074, 1034, 966, 897 found 443.978 (error 4.5 ppm)
4.51 (2H, dq, J ˆ 9, 7, 113.3 (dtq, J ˆ 9, 255, 37, CF2), CF3), ÿ75.2 (3F, t, J ˆ 8,
OCH2CF3) 64.3 (q, J ˆ 39, OCH2CF3), CH2CF3)
63.4 (t, J ˆ 30, OCH2CF2)
22 5.92 (2H, tt, J ˆ 4, 36, CF2H), 122 (dq, J ˆ 11, 278, CF3), ÿ137.3 (4F, d, J ˆ 52, ÿ3.6 1458, 1423, 1282 (P=O), 1240, Calculated C8H8F11O4P 407.998
4.46 (4H, dtt, J ˆ 8, 1, 12, 113.3 (dtt, J ˆ 9, 29, 250, CF2H), ÿ124.5 (4F, t, 1184, 1076, 964, 899, 835 ([M±F]‡ˆ389.000), found
OCH2CF2CF2), 4.42 (2H, dq, CH2CF2), 109 (tt, J ˆ 39, 251, J ˆ 13, CH2CF2), 388.998 (error 4.2 ppm)

C.M. Timperley et al. / Journal of Fluorine Chemistry 106 (2000) 153±161

J ˆ 8, 9, OCH2CF3) CF2H), 64.3 (dq, J ˆ 5, 39, ÿ75.3 (3F, t, J ˆ 6, CF3)
CH2CF3), 63.6 (dt, J ˆ 6, 30,
CH2CF2)
23 4.55 (4H, dt, J ˆ 9, 13, 121.9 (dq, J ˆ 10, 278, CH2CF3), ÿ126.7 (4F, br m, CH2CF2), ÿ3.8 1458, 1356, 1282 (P=O), 1230, Calculated C10H6F17O4P
OCH2CF2), 4.43 (2H, dq, 115-110 (m, J obs, CF2CF2), ÿ120.9 (4F, br m, CF2), 1182, 1082, 1016, 966, 930 543.973, found 543.972
J ˆ 9, 8, OCH2CF3) 107 (m, J obs, CF3), ÿ80.1 (6F, t, J ˆ 10, CF3), (error 2.8 ppm)
64.4 (dq, J ˆ 4, 38, CH2CF3), ÿ74.7 (3F, t, J ˆ 9, CH2CF3)
63.6 (br t, J ˆ 26, CH2CF2)
24 4.51 (2H, dtq, J ˆ 8, 12, 1, 122 (dq, J ˆ 10, 278, CH2CF3), ÿ124.5 (2F, m, CH2CF2), ÿ3.8 1459, 1424, 1305, 1279 (P=O), Calculated C7H6F11O4P 393.983,
OCH2CF2), 4.43 (4H, dq, 118 (tq, J ˆ 34, 286, CF3), ÿ83.3 (3F, m, CF3), 1179, 1081, 1033, 965, 898, found 393.982 (error 0.9 ppm)
J ˆ 9, 8, OCH2CF3) 113 (dtq, J ˆ 8, 38, 278, CF2), ÿ75.2 (6F, m, CH2CF3) 845, 810
64.3 (dq, J ˆ 5, 38, CH2CF3),
63.3 (dt, J ˆ 4, 29, CH2CF2)
25 5.92 (1H, tt, J ˆ 4, 56, 122.1 (dq, J ˆ 9, 278, CF3), ÿ137.2 (2F, m, J ˆ 61, ÿ3.7 1458, 1424, 1274 (P=O), 1239, Calculated C7H7F10O4P 375.992,
CF2H), 4.48 (2H, br dt, 113.5 (dtt, J ˆ 9, 28, 250, CF2), CF2H), ÿ124.5 (2F, br m, 1109, 964, 938, 898, 840 found 375.990 (error 6.8 ppm)
J ˆ 8, OCH2CF2), 4.43 (4H, dq, 109.1 (tt, J ˆ 36, 251, CF2H), CF2), ÿ75.2 (6F, br m, CF3)
J ˆ 9, 8, OCH2CF3) 64.4 (dq, J ˆ 5, 38, OCH2CF3),
63.8 (dt, J ˆ 4, 29, OCH2CF2)
26 4.6 (2H, dt, J ˆ 7, 13, 121.9 (dq, J ˆ 13, 280, OCH2CF3), ÿ126.5 (2F, m, OCH2CF2), ÿ3.7 1458, 1306, 1279 (P=O), 1234, Calculated C8H6F13O4P 443.980,
OCH2C3F7), 4.43 (4H, dq, 117.4 (tq, J ˆ 39, 287, CF2CF2CF3), ÿ121 (2F, m, CF2CF3), 1182, 1086, 1016, 966, found 443.789 (error 2.1 ppm)
J ˆ 8, 8, OCH2CF3) 113 (dtt, J ˆ 10, 33, 258, OCH2CF2), ÿ80 (3F, CF2CF3), 903, 845
109 (tq, J ˆ 271, 37, CF2CF2CF3) ÿ72.5 (6F, m, CH2CF3)
27 5.91 (1H, tt, J ˆ 3, 52, CF2H), 118.1 (tq, J ˆ 33, 288, CF3), ÿ136.4 (2F, d, J ˆ 52, ÿ3.8 1460, 1356, 1306 (P=O), 1209, Calculated C9H7F14O4P 475.986,
4.5 (4H, m, J ˆ 8, 14, OCH2CF3), 111 (m, J obs, 64, both types of CF2), CF2H), ÿ123.6 (2F, t, 1113, 1070, 1032, 937, 897, found 475.983 (error 5 ppm)
4.48 (2H, m, J ˆ 8, 6, 109 (tt, J ˆ 36, 251, CF2H), J ˆ 14, CF2CF2H), 835
OCH2CF2CF2H) 63.7 (dt, J ˆ 6, 31, CH2CF2CF2), ÿ123.6 (4F, t, J ˆ 13,
63.4 (dt, J ˆ 5, 29, CH2C2F5) CF2CF3), ÿ82.6 (6F, s, CF3)
28 4.55 and 4.51 (4H, each pair ddd, 118.3 (tq, J ˆ 36, 284, CH2CF2CF3), ÿ126.6 (2F, m, CF2CF2), ÿ3.9 1460, 1377, 1356, 1307 (PˆO), Calculated C10H6F17O4P
J ˆ 7, 13, one of coupling 117.7 (tq, J ˆ 29, 287), 111.5 (dtq, ÿ123.8 (4F, m, CF2CF3), 1209, 1126, 1074, 1034, 543.973, found 543.971
constants obscured because of J ˆ 9, 257, 36, CH2CF2CF3), 111 and ÿ120.9 (2F, m, CF2C2F5), 937, 897, 820 (error 3.3 ppm)
overlap, pair of enantiotopic 107 (m, J obs, CH2CF2CF2), 63.8 (dt, ÿ82.7 (6F, m, CF2CF3),
protons in OCH2C2F5 groups), J ˆ 4, 27, OCH2C3F7), 63.6 (dt, J ˆ 4, ÿ80 (3F, m, CF2CF2CF3)
4.51 (2H, dt, J ˆ 8, 12, 29, OCH2C2F5)
OCH2C3F7)
a
In the carbon spectra, obs indicates that the signals are obscured due to complex splitting patterns and signal-to-noise problems.
 C.M. Timperley et al. / Journal of Fluorine Chemistry 106 (2000) 153±161 159

3. Conclusion 4.1. Reaction of fluoroalcohols with phosphorus

pentachloride
Symmetrical ¯uoroalkyl phosphates can be prepared
from the interaction of primary or secondary ¯uoroalcohols The ¯uoroalcohol (0.2 mol) was added dropwise using a
with phosphorus pentachloride; tertiary ¯uoroalcohols pressure-equalising dropping funnel (equipped with a cal-
do not react under these conditions. A requirement for a cium chloride guard tube) to ®nely-divided phosphorus
high yield of phosphate is the presence of many ¯uorine pentachloride (0.05 mol) in a round-bottom ¯ask cooled
atoms in the ¯uoroalcohol. With hexa¯uoroisopropanol to 0±58C. Contact of the ¯uoroalcohol with the solid phos-
the reaction followed a surprising course, giving phorus pentachloride resulted in dissolution, giving a col-
the expected symmetrical phosphate and the unexpected ourless solution that effervesced due to liberation of HCl and
tetra-(hexa¯uoroisopropoxy) chlorophosphorane. This out- the respective ¯uoroalkyl chloride. After addition, the mix-
come indicates that ¯uoroalcoholysis of PCl5 is mediated ture was warmed to room temperature and left for 12 h. An
through chlorophosphorane intermediates, rather than by aliquot was then analysed by GC±MS. In cases where good
formation of POCl3 and its subsequent transformation conversion to the required product had occurred, residual
(as proposed by Chuganov and Sapgir [5]). Unsymmetri- phosphorus pentachloride was removed by ®ltration. Frac-
cal ¯uoroalkyl phosphates can be prepared from the tionation under reduced pressure (0.015±0.9 mmHg) gave
interaction of primary ¯uoroalcohols with phosphoryl tris(¯uoroalkyl)phosphates 7±11 and 18 as colourless
chlorides in the presence of calcium chloride; secondary liquids. Yields ranged from 10 to 76% (see Table 1).
or tertiary ¯uoroalcohols are unreactive under these
conditions. 4.2. Reaction of hexafluoroisopropanol with phosphorus
pentachloride

4. Experimental details The previous procedure was followed. As some unreacted

phosphorus pentachloride remained after addition of hexa-
All reagents were of commercial quality: ¯uoroalcohols ¯uoroisopropanol, the mixture was re¯uxed for 2 h, then
were purchased from Apollo Scienti®c Ltd (Derbyshire, distilled under reduced pressure (bp 408C/0.08 mmHg).
UK) or from Lancaster Synthesis (Morecambe, UK). Anhy- Multinuclear NMR analysis showed the distillate to com-
drous solvents were used for reactions. NMR spectra were prise 30% tris(hexa¯uoroisopropyl)phosphate 12a and 70%
obtained on a JEOL Lambda 500 instrument (operating at tetra(hexa¯uoroisopropoxy)chlorophosphorane 12b. A por-
500 MHz for 1 H, 125 MHz for 13 C, 470 MHz for 19 F, and tion of the mixture (10 g) was treated with ice water (5 g) in
202 MHz for 31 P spectra) or a JEOL Lambda 300 instrument chloroform (20 ml). The product, the lowest of three layers,
(operating at 300 MHz for 1 H, 75 MHz for 13 C, 282 MHz for was separated and concentrated under reduced pressure to
19
F, and 121.5 MHz for 31 P spectra) as solutions in CDCl3, give pure tris(hexa¯uoroisopropyl)phosphate 12a as white
with internal reference SiMe4 for 1 H and 13 C, external crystals (11.2 g, 92%); mp 248C (lit. mp 238C [11]). HRMS
CFCl3 for 19 F and external (MeO)3P (d 140 ppm) for 31 P for phosphorane 12b: calculated for C12H4ClF24O4P
spectra. Data in Tables 2 and 4 are recorded as follows: 733.915 ([M±FŠ‡ ˆ 714:917 and [M±ClŠ‡ ˆ 698:946),
chemical shifts in ppm from reference on the d scale, found 714.916 (error 1.1 ppm) and 698.946 (error 1.1 ppm).
integration, multiplicity (s: singlet, d: doublet, t: triplet, q:
quartet, m: multiplet and sep: septet, br: broad, obs: 4.3. Attempted synthesis of tris(2,2,3,3-
obscured signal from which coupling constants could tetrafluorocyclobutyl) phosphate
not be extracted), coupling constant (Hz) and assignment.
IR spectra were recorded as liquid ®lms on a Nicolet The method was essentially the same as that outlined in
SP210 instrument using Omnic sofware. Reaction mixtures Section 4.1. After addition of 2,2,3,3-tetra¯uorocyclobuta-
were monitored by gas chromatography±mass spectrometry nol 19, the reaction mixture set solid and was left for 14 h.
(GC±MS) using a Finnigan MAT GCQ instrument with On heating, it melted and the resulting liquid was re¯uxed
chemical ionisation (CI) using methane as reagent gas. for 3 h, then distilled to give a colourless oil (bp 1188C/
Molecular masses of pure products were con®rmed 0.5 mmHg) which on standing crystallised to give a
with methane ‡ve CI data. Elemental analysis was carried white solid (mp 40±428C). The solid contained two
out on the largest stable fragment ion, using high resolution phosphorus compounds that were not separated or charac-
mass spectrometry (HRMS) on a Micromass Autospec terised.
SQ Double Focusing Magnetic Sector instrument.
Mode: ‡ve ion electron impact, magnet scan m/z 400± 4.4. Attempted synthesis of tris[(perfluorocyclohexyl)
100 (seconds/decade), resolution 2900. Inlet: septum methyl] phosphate
(1608C), 0.2 ml introduced. Source conditions: temperature
2008C, electron energy 70 eV, and accelerating voltage The method was essentially the same as that outlined in
8000 V. Section 4.1. After addition of the (per¯uorocyclohexyl)-
160 C.M. Timperley et al. / Journal of Fluorine Chemistry 106 (2000) 153±161

methanol 20, the mixture was allowed to warm to room pressure gave the title compound as a colourless mobile
temperature and then re¯uxed for 6 h (until all the solid went liquid (51.8 g, 77%); bp 738C/5 mmHg.
into solution) to produce a very viscous oil. The oil was
distilled (bp 1348C/0.01 mmHg) and shown by multinuclear 4.9. Attempted reaction of unsymmetrical phosphate (24)
NMR analysis to contain ®ve different phosphorus com- with butanol or propylamine
pounds. No attempt was made to separate or characterise the
individual compounds. Butanol or propylamine (6 mmol) were introduced by
syringe into a solution of bis(2,2,2-tri¯uoroethyl) 2,2,3,3,3-
4.5. Methanolysis of tetra(1,1,1,3,3,3- penta¯uoropropyl phosphate 24 (6 mmol) in dichloro-
hexafluoroisopropoxy)chlorophosphorane (12b) methane (10 ml) at room temperature under argon. Analysis
by GC±MS showed no reaction to have taken place after
The 3:7 mixture of tris(hexa¯uoroisopropyl)phosphate 12 h. The starting phosphate was recovered by distillation
12a and tetra(hexa¯uoro-isopropoxy)chlorophosphorane under reduced pressure (bp 528C/1 mmHg).
12b (2 g), made according to the procedure in Section
4.2, was weighed into an oven-dried separating funnel
and methanol added by syringe (0.1 ml). The methanol Acknowledgements
formed a top layer that dissolved slowly with evolution
of HCl gas. Analysis by GC±MS and NMR spectro- Many thanks to Alison Bussey and Steve Marriott for
scopy showed the mixture to comprise phosphate 12a, providing the infrared data. We also wish to thank DERA
tetra(hexa¯uoroisopropoxy)methoxyphosphorane 13, bis- Haslar (Environmental Sciences) for funding the work.
(hexa¯uoroisopropyl) methyl phosphate 15, dimethyl hexa-
¯uoroisopropyl phosphate 16 and trimethyl phosphate.
References
4.6. The synthesis of bis(fluoroalkyl) 2,2,2-trifluoroethyl
phosphates (21)±(23) [1] I.L. Knunyants, O.V. Kil'dasheva, E. Bykovskaya, Zh. Obshch.
Khim. 19 (1949) 93 (English Translation).
2,2,2-Tri¯uoroethyl phosphorodichloridate 3 (10 mmol) [2] F. Swarts, Recl. Trav. Chim. Pays-Bas 28 (1909) 166.
was weighed into a 25 ml round-bottom ¯ask equipped with [3] T.N. Sintashina, V.F. Mironov, E.N. Ofitserov, I.V. Konovalova, A.N.
Pudovik, Izv. Akad. Nauk. SSSR (1988) 1451, Chem. Abs. 95 (1989)
a magnetic ¯ea and a Liebig condenser with a calcium 186571.
chloride guard tube. To the reaction mixture was added [4] L.C. Krogh, T.S. Reid, H.A. Brown, J. Org. Chem. 19 (1954) 1124.
®nely powdered anhydrous CaCl2 (0.5 mmol) in one portion [5] V.S. Chuganov, E.V. Sapgir, Zh. Obshch. Khim. 38 (1968) 412
and the appropriate ¯uoroalcohol (20 mmol) by syringe. The (English Translation).
mixture was maintained at 1508C for 2 h. Evolution of HCl [6] L.S. Zakharov, V.V. Pisarenko, N.N. Godovikov, M.I. Kabachnik, Izv.
Akad. Nauk. SSSR, Ser. Khim. (1969) 1729 (English Translation).
was observed; beads of hydrochloric acid formed on the [7] L.S. Zakharov, V.V. Pisarenko, N.N. Godovikov, M.I. Kabachnik,
inner surface of the guard tube. The reaction mixture was Bull. Acad. Sci. USSR, Div. Chem. Sci. 20 (1971) 2373 (English
analysed by GC±MS. The title compounds were isolated Translation).
after fractionation in a micro-distillation apparatus. [8] K. Sellars, J. Appl. Chem. (London) 6 (1956) 45.
[9] J.C. Conly, US Patents 2 754 316, 2 754 317 and 2 754 318 (1956);
Chem. Abs. 51 (1957) 1244.
4.7. General procedure for the synthesis of unsymmetrical [10] I. Yu Kudryavtsev, L.S. Zakharov, M.I. Kabachnik, Russ. Chem.
phosphates (24)±(28) Bull. 47 (1998) 2015.
[11] D. Dakternieks, G.V. Roschenthaler, R. Schmutzler, J. Fluorine
The procedure was the same as that in the previous Chem. 1 (1978) 387.
section, only bis(2,2,2-tri¯uoroethyl)phosphorochloridate [12] A.F. Benning, US Patent 2 597 702 (1952), Chem. Abs. 47 (1953)
2196c
4 or bis(2,2,3,3,3-penta¯uoropropyl)phosphorochloridate 5 [13] P.O. Gitel', L.F. Osipova, O.P. Solovova, A.Ya Yakubovich, Zh.
(10 mmol) was treated with the appropriate ¯uoroalcohol Obshch. Khim. 39 (1969) 281 (English Translation).
(10 mmol). [14] A.V. Fokin, V.A. Komarov, A.F. Kolomiets, A.I. Rapkin, K.I.
Pasevina, T.M. Potarina, O.V. Verenikin, Izv. Akad. Nauk. SSSR,
4.8. Scaled-up synthesis of bis(2,2,2-trifluoroethyl) Ser. Khim. 7 (1978) 1375 (English Translation).
[15] A.V. Fokin, N. Studnev, A.I. Rapkin, K.I. Posevina, A.F. Kolomiets,
2,2,3,3,3-pentafluoropropyl phosphate (24) Izv. Akad. SSSR Ser. Khim. 7 (1981) 1641.
[16] M.I. Kabachnik, L.S. Zakharov, E.I. Goryunov, I.Yu. Kudryavtsev,
Finely-powdered anhydrous CaCl2 (0.9 g, 8.5 mmol) G.N. Molchanova, M.A. Kurykin, P.V. Petrovskii, T.M. Shcherbina,
was added in one portion to a magnetically stirred mixture A.P. Laretina, Russ. J. Gen. Chem. 64 (1994) 812 (English
of bis(2,2,2-tri¯uoroethyl)phosphorochloridate 4 (47.5 g, Translation).
[17] C.M. Timperley, I.J. Morton, M.J. Waters, J.L. Yarwood, J. Fluorine
0.17 mol) and 2,2,3,3,3-penta¯uoropropanol (21.5 g, Chem. 96 (1999) 95.
0.17 mol). The mixture was heated under re¯ux for 4 h. [18] C.M. Timperley, M. Bird, J.F. Broderick, I. Holden, I.J. Morton, M.J.
Evolution of HCl took place. Fractionation under reduced Waters, J. Fluorine Chem. (2000), in press.
 C.M. Timperley et al. / Journal of Fluorine Chemistry 106 (2000) 153±161 161

[19] C.M. Timperley, Highly Toxic Fluorine Compounds, in: R.E. Banks [26] L.S. Zakharov, E.I. Goryunov, S.T. Ioffe, L.L. Morozov, T.M.
(Ed.), Fluorine Chemistry at the Millennium: Fascinated by Fluorine, Shcherbina, M.I. Kabachnik, Izv. Akad. Nauk. SSSR Ser. Khim. 8
Chapter 29, 2000, in press. (1976) 1727 (English Translation).
[20] L.N. Markovskii, A.V. Solov'ev, V.E. Pashinnik, Y.G. Shermolovich, [27] L.S. Zakharov, E.I. Goryunov, L.L. Morozov, V.A. Svoren', E.P.
Zh. Obshch. Khim. 50 (1980) 644 (English Translation). Lur'e, T.M. Shcherbina, M.I. Kabachnik, Izv. Akad. Nauk. SSSR,
[21] D.B. Denney, D.Z. Denney, P.J. Hammond, Y.-P. Wang, J. Am. Ser. Khim. 9 (1978) 1843 (English Translation).
Chem. Soc. 103 (1981) 1785. [28] E.I. Goryunov, L.S. Zakharov, P.V. Petrovskii, M.I. Kabachnik, Izv.
[22] T. Kubota, S. Miyashita, T. Kitazume, N. Ishikawa, J. Org. Chem. 45 Akad. Nauk. SSSR, Ser. Khim. 7 (1984) 1463 (English Translation).
(1980) 5052. [29] E.I. Goryunov, L.S. Zakharov, P.V. Petrovskii, M.I. Kabachnik, Izv.
[23] L.S. Zakharov, V.V. Pisarenko, N.N. Godovikov, M.I. Kabachnik, Akad. Nauk. SSSR, Ser. Khim. 4 (1985) 799 (English Translation).
Bull. Acad. Sci. USSR, Div. Chem. Sci., 20 (1971) 2536 (English [30] E.I. Goryunov, P.V. Petrovskii, T.M. Shcherbina, L.S. Zakharov, M.I.
Translation). Kabachnik, Izv. Akad. Nauk. SSSR, Ser. Khim. 8 (1989) 1700
[24] M.I. Kabachnik, L.S. Zakharov, E.I. Goryunov, V.S. Shaidurov, A.V. (English Translation).
Kashkin, Y.L. Bakhmutov, V.F. Zabolotskikh, Izv. Akad. Nauk. [31] E.I. Goryunov, P.V. Petrovskii, L.S. Zakharov, M.I. Kabachnik, Izv.
SSSR, Ser. Khim. 4 (1985) 875 (English Translation). Akad. Nauk. SSSR, Ser. Khim. 2 (1990) 371 (English Translation).
[25] L.S. Zakharov, V.V. Pisarenko, N.N. Godovikov, M.I. Kabachnik, Izv. [32] E.I. Goryunov, G.N. Molchanova, P.V. Petrovskii, L.S. Zakharov,
Akad. Nauk. SSSR Ser. Khim. 12 (1969) 2699 (English Translation). M.I. Kabachnik, Russ. Chem. Bull. 47 (1998) 1728.