Fluorinated phosphorus compounds: Part 1. The synthesis and reactions of some fluoroalkyl phosphoryl compounds

Article abstract of DOI:10.1016/S0022-1139(00)00248-7

Fluoroalkyl phosphorochloridates CF₃CH₂OP(O)Cl₂ and (R_FCH₂O)₂P(O)Cl (R_F=CF₃, C₂F₅) were prepared from phosphorus oxychloride, fluoroalcohols and triethylamine, but selective substitution was difficult. Phosphates (R_FCH₂O)₂P(O)OR (R_F=CF₃, C₂F₅ and R=Me, Et, n-Pr, i-Pr) were isolated in yields of 38-84% from the reactions of the phosphorochloridates with alcohols and triethylamine. Success of the inverse reaction, i.e. ROP(O)Cl₂ and R_FCH₂OH, depended on the R group (Me, Et) and the R_F group (CF₃, C₂F₅). The phosphates did not react with bromotrimethylsilane in chloroform. Addition of amines to CF₃CH₂OP(O)Cl₂ or (CF₃CH₂O)₂P(O)Cl gave phosphoramidates (RR′N)₂P(O)OCH₂CF₃ or (CF₃CH₂O)₂P(O)NRR′ (R and R′=H, Me, Et) in yields of 58-75%. The inverse reactions of Me₂NP(O)Cl₂ and (Me₂N)₂P(O)Cl with trifluoroethanol were slow, but were catalysed by 4-dimethylaminopyridine. Anhydrous hydrogen chloride split one of the P-N bonds of (Me₂N)₂P(O)OCH₂CF₃ to give Me₂NP(O)Cl(OCH₂CF₃), but was without action on (CF₃CH₂O)₂P(O)NMe₂.

Full text of DOI:10.1016/S0022-1139(00)00248-7

Journal of Fluorine Chemistry 104 (2000) 215±223
Fluorinated phosphorus compounds
Part 1. The synthesis and reactions of some
¯uoroalkyl phosphoryl compounds
Christopher M. Timperley*, Michael Bird, John F. Broderick,
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 16 December 1999; accepted 20 January 2000
Abstract
Fluoroalkyl phosphorochloridates CF3CH2OP(O)Cl2 and (RFCH2O)2P(O)Cl (RFˆCF3, C2F5) were prepared from phosphorus
oxychloride, ¯uoroalcohols and triethylamine, but selective substitution was dif®cult. Phosphates (RFCH2O)2P(O)OR (RFˆCF3, C2F5
and RˆMe, Et, n-Pr, i-Pr) were isolated in yields of 38±84% from the reactions of the phosphorochloridates with alcohols and
triethylamine. Success of the inverse reaction, i.e. ROP(O)Cl2 and RFCH2OH, depended on the R group (Me, Et) and the RF group
(CF3, C2F5). The phosphates did not react with bromotrimethylsilane in chloroform. Addition of amines to CF3CH2OP(O)Cl2 or
(CF3CH2O)2P(O)Cl gave phosphoramidates (RR0N)2P(O)OCH2CF3 or (CF3CH2O)2P(O)NRR0 (R and R0ˆH, Me, Et) in yields of 58±75%.
The inverse reactions of Me2NP(O)Cl2 and (Me2N)2P(O)Cl with tri¯uoroethanol were slow, but were catalysed by 4-dimethylaminopyr-
idine. Anhydrous hydrogen chloride split one of the P±N bonds of (Me2N)2P(O)OCH2CF3 to give Me2NP(O)Cl(OCH2CF3), but was
without action on (CF3CH2O)2P(O)NMe2. # 2000 Elsevier Science S.A. All rights reserved.
Keywords: Alkyl bis(¯uoroalkyl) phosphate; Bis(¯uoroalkyl) phosphorochloridate; Fluoroalcohol; Phosphate; Phosphoramidate
1. Introduction
phosphorus atom (termed SN2P) [1]. Nucleophilic attack
on bis(¯uoroalkyl) phosphorochloridate A,1 for example,
gives intermediate B which collapses to product C. The rate
is accelerated by the presence of electronegative substituents
in the phosphorochloridate. For example, bis(tri¯uoroethyl)
phosphorochloridate (CF3CH2O)2P(O)Cl is more electro-
philic than its un¯uorinated counterpart (CH3CH2O)2-
P(O)Cl (a tri¯uoroethyl group is more electronegative
than an ethyl group: the pKa of CF3CH2OH is 12.4 while
that of CH3CH2OH is 15.9 [2]).
Although the organic chemistry of phosphorus has been
studied for over a century, the possibilities offered by the
introduction of ¯uoroalkyl groups have only just begun to be
realised. Indeed, the carbon±¯uorine system forms the basis
of a new branch of organophosphorus chemistry, paralleling
the huge and better-known ®eld arising from carbon and
hydrogen. The range of compounds capable of existence is
thus enormous, particularly since mixed ¯uorohydrocarbon
species, and their derivatives, are usually stable, and can give
rise to vast numbers of isomers, all of which present new
challenges. Of particular interest is the selective incorpora-
tion of ¯uoroalkoxy groups into pentavalent phosphorus
compounds, which should enhance their phosphorylating
ability.
The mechanism of phosphorylation is generally inter-
preted as a bimolecular displacement proceeding at the
1 Organic phosphorus compounds are named after the corresponding
parent acids. Most compounds described in this paper are derivatives of
phosphoric acid (HO)3P=O. For example, the acid chloride (RFCH2O)2-
P(O)Cl is a bis(fluoroalkyl) phosphorochloridate [i.e. a diester of
phosphorochloridic acid (HO)2P(O)Cl] and the amide (RFCH2O)2-
P(O)NMe2 is a bis(fluoroalkyl) N,N±dimethylphosphoramidate [i.e. a
diester of N,N±dimethylphosphoramidic acid (HO)2P(O)NMe2].
* Corresponding author. Tel.: ‡44-1980-613566;
fax: ‡44-1980-613371.
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 2 4 8 - 7

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C.M. Timperley et al. / Journal of Fluorine Chemistry 104 (2000) 215±223
The rate of substitution also depends on the basicity and
The use of two molar equivalents of ¯uoroalcohol gave
bis and tris-substitution products, fractionation furnishing
monochlorides 2 and 3 in moderate yields.
size of the nucleophile. While the reactions of alkyl phos-
phorochloridates have been widely explored, those of
¯uoroalkyl phosphorochloridates have remained largely
uncharted. Previously, we described the synthesis of dialkyl
¯uoroalkyl phosphates from dialkyl phosphorochloridates
and ¯uoroalcohols [3]. In this paper, the reactions of ¯uor-
oalkyl phosphorochloridates 1±3 with some oxygen and
nitrogen nucleophiles are reported.
Unlike bis(2-¯uoroethyl) phosphorochloridate (FCH2CH2-
O)2P(O)Cl which rapidly decomposes on standing [7],
compounds 2 and 3 are stable when stored in the absence
of moisture.
This work is part of a wider study on the effects of
¯uoroalkyl groups on the physicochemical properties of
pentavalent phosphorus compounds. The reactivities of
some ¯uoroalkyl phosphates and phosphoramidates towards
electrophiles are also discussed.
2.2. Synthesis of alkyl bis(fluoroalkyl) phosphates
The ®rst example of an unsymmetrical phosphate bearing
a ¯uoroalkyl group is diethyl 2-¯uoroethyl phosphate
(EtO)2P(O)OCH2CH2F, prepared by Saunders et al. in
1945, by the addition of diethyl phosphorochloridate to
2-¯uoroethanol and pyridine in ether [10]. Recently, we
showed that treatment of dialkyl phosphorochloridates with
¯uoroalcohols gave related phosphates of structure
(RO)2P(O)OCH2RF [3]. A logical extension to this work
was to investigate ways of preparing phosphates of structure
(RFCH2O)2P(O)OR. Accordingly, it was found that treat-
ment of chlorides 2 or 3 with alcohols in the presence of
triethylamine afforded the desired phosphates 4±9 in rea-
sonable yields (Table 1).
2. Results and discussion
2.1. Synthesis of fluoroalkyl phosphorochloridates
One route to alkyl phosphorodichloridates ROP(O)Cl2
involves alcoholysis of phosphorus oxychloride, with
removal of hydrogen chloride by passage of nitrogen
through the reactants [4]. This method can be used for
¯uoroalkyl phosphorodichloridates RFOP(O)Cl2 only in
cases where the ¯uoroalcohol has few ¯uorine atoms.
One or two molar equivalents of 2-¯uoroethanol (pKa
14.4 [5]) gave FCH2CH2OP(O)Cl2 in 34% yield [6] or
(FCH2CH2O)2P(O)Cl in 11% yield [7]. Poly¯uorinated
alcohols, such as tri¯uoroethanol, do not react under these
conditions; the acidity of CF3CH2OH (pKa 12.4) approaches
that of phenol (pKa 10 [2]) and its reactivity parallels that of
phenol rather than that of an un¯uorinated primary alcohol.
A base is required to initiate phosphorylation. Phenol [8]
and tri¯uoroethanol [9] reacted with POCl3 in the presence
of pyridine to give mixtures of substitution products, regard-
less of the ratios of the reactants. The inductive effect of the
¯uoroalkoxy group is analogous to that of a phenoxy group
and predominates in phosphorus compounds.
Selective mono or bis substitution of phosphorus oxy-
chloride by ¯uoroalcohols might be complicated by the
formation of polysubstituted by-products. It was, therefore,
of interest to examine the reactions of POCl3 with ¯uor-
oalcohols in the presence of triethylamine.
An equimolar ratio of phosphorus oxychloride and tri-
¯uoroethanol gave mono, bis and tris-substitution products,
with dichloridate 1 predominating. The latter was isolated in
95% purity by careful fractionation of the mixture.
Table 1
Experimental data for alkyl bis(fluoroalkyl) phosphates (RFCH2O)2-
P(O)ORa
Compound
RF
R
Yield
(%)
Boiling point
(8C/mm Hg)
4
5
6
7
8
9
CF3
C2F5
CF3
C2F5
CF3
CF3
Me
Me
Et
44
42/0.1
84
43±45/0.06
37/0.01
60b
50b
70
Et
45±46/0.04
45/0.015
37/0.015
n-Pr
i-Pr
38
a Prepared by addition of an alcohol and triethylamine to the
appropriate bis(fluoroalkyl) phosphorochloridate.
b Compounds 6 and 7 were also made by addition of the respective
fluoroalcohols and triethylamine to ethyl phosphorodichloridate in yields
of 52 and 35% respectively.

Table 2
Spectroscopic data for alkyl bis(fluoroalkyl) phosphates (RFCH2O)2P(O)OR (NMR data measured in CDCl3)
1
Compound
1H NMR d, J (Hz)
13C NMR d, J (Hz)
19F NMR d, J (Hz)
31P NMR d
IR n(cm
)
HRMS analysis
4
4.4 (4H, m, OCH2),
3.88 (3H, d, Jˆ11, OCH3)
122.2 (dq, Jˆ9, 277, CF3),
63.9 (dq, Jˆ4, 38, OCH2),
55.3 (d, Jˆ7, OCH3)
118.1 (tq, Jˆ34, 285,
CF3), 111.3 (tq, Jˆ8,
256, CF2), 63 (dq, Jˆ5,
38, OCH2), 55.3 (d,
Jˆ7, OCH3)
74.5 (6F, t, Jˆ8, CF3)
2.2
1302 (P=O), 1276, 1178,
1119, 1084, 1056, 965, 877
Calc. C5H7F6O3P 275.999
‡
([M H] ˆ274.991),
found 274.992 (error 3.4)
Calc. C7H7F10O3P 375.992,
found 375.993 (error 2.6)
5
6
7
4.48 (4H, br m, OCH2),
82.9 (6F, qt, Jˆ287, 118,
35, CF3), 124.1 (4F,
t, Jˆ12, CF2)
2.4
3.4
3.5
1460, 1356, 1302 (P=O),
1205, 1159, 1112, 1065,
1032, 937, 885
3.87 (3H, d, Jˆ11, OCH3)
4.45 (4H, m, OCH2CF3),
4.31 (2H, dq, Jˆ7, OCH2),
1.38 (3H, t, Jˆ7, CH3)
121.5 (dq, Jˆ9, 277, CF3),
65.7 (m, Jˆ7, OCH2),
63.8 (dq, Jˆ5, 38,
74.4 (6F, t, Jˆ8, CF3)
1458, 1423, 1374,
1301 (P=O), 1275, 1178,
1117, 1086, 1041, 965, 893,
842
Calc. C6H9F6O3P 290.014
‡
([M H] ˆ289.006),
found 289.007 (error 0.7)
OCH2CF3), 15.8 (m, Jˆ6,
CH3)
4.46 (4H, br m, OCH2CF3),
4.23 (2H, dq, Jˆ8, 7, OCH2),
1.39 (3H, dt, Jˆ1, 7, CH3)
118 (tq, Jˆ35, 118, 287,
CF3), 111.4 (tq, Jˆ8, 256,
CF2), 65.7 (m, Jˆ7,
OCH2), 62.7 (dt,
82.8 (6F, qt, Jˆ287, 118,
35, CF3), -124 (4F, t,
Jˆ12, CF2)
1482, 1460, 1408, 1375,
1355, 1301 (P=O), 1206,
1159, 1111, 1071, 1032,
984, 937, 888
Calc. C8H9F10O3P 390.008
‡
([M H] ˆ389.000),
found 388.999 (error 3.2)
Jˆ5, 29, OCH2CF2),
15.5 (m, Jˆ6, CH3)
122.3 (dq, Jˆ9, 277, CF3),
71 (OCH2), 63.8 (dq,
Jˆ5, 38, OCH2CF3),
23.3 (CH2), 9.7 (CH3)
8
9
4.37 (4H, m, OCH2CF3),
4.12 (2H, dt, Jˆ7, 7,
OCH2), 1.76 (2H, tq,
Jˆ7, CH2), 0.98 (3H,
t, Jˆ7, CH3)
77.0 (6F, t, Jˆ8, CF3)
74.4 (6F, t, Jˆ8, CF3)
3.3
4.4
1300 (P=O), 1274, 1176,
1084, 1057, 1027, 965, 891
Calc. C7H11F6O3P 304.030
‡
([M H] ˆ303.022),
found 303.021 (error 4.1)
5.8 (1H, dsep, Jˆ7, OCH),
4.35 (4H, m, OCH2CF3),
1.4 (6H, d, Jˆ7, CH3)
122.4 (dq, Jˆ9, 277, CF3),
75.7 (m, Jˆ6, OCH),
1471, 1458, 1424,
1300 (P=O), 1272, 1174,
1123, 1083, 1020, 966, 891,
844
Calc. C7H11F6O3P 304.030
‡
([M H] ˆ303.022),
63.8 (dq, Jˆ5, 33, OCH2),
23.4 (m, Jˆ4, CH3)
found 303.022 (error 1.2)

218
C.M. Timperley et al. / Journal of Fluorine Chemistry 104 (2000) 215±223
An alternative route utilises the reaction between an alkyl
This lack of reactivity provides further evidence that the
reaction of bromotrimethylsilane with ¯uoroalkyl phos-
phates is mediated through attack of the OR group rather
than the P=O group (attack by the phosphoryl group occurs
with un¯uorinated phosphates [12]).
phosphorodichloridate and a ¯uoroalcohol. Treatment of
methyl phosphorodichloridate with two equivalents of tri-
¯uoroethanol or penta¯uoropropanol, however, gave bis
phosphates 4 and 5, in addition to tris phosphates 4a and
5a, and the mixtures could not be separated by distillation.
2.4. Synthesis of fluoroalkyl phosphoramidates
Amines are more basic than alcohols and tend to phos-
phorylate more readily. The synthesis of phosphorus amides
from alkyl phosphorochloridates is well documented [13±
15], but their preparation from ¯uoroalkyl phosphorochlor-
idates is restricted to a few compounds [9,16]. In this study,
the reactions of tri¯uoroethyl phosphorodichloridate and
bis(tri¯uoroethyl) phosphorochloridate with various alipha-
tic amines were examined.
Treatment of dichloride 1 with secondary amines gave
phosphorodiamidates 10±12 in yields of 58±70% (Table 3).
The reaction rate depended on the size of the amine and
decreased in the order Me2NH>MeEtNH>Et2NH.
The P±OMe bonds of phosphates 4 and 5 are weakened
by the electronegative tri¯uoroalkyl groups, which enables
transesteri®cation by the ¯uoroalcohols and departure of
methanol. The greater nucleophilicity of tri¯uoroethanol
compared to penta¯uoropropanol may account for the
greater proportion of 4a over 5a in the mixtures.
With ethyl phosphorodichloridate, unsymmetrical phos-
phates 6 and 7 formed exclusively. The P±OEt bond is
generally stronger than the P±OMe bond, and consequently,
the ethyl phosphates are not attacked by ¯uoroalcohols.
Similarly, monochloride 2 combined with primary and
secondary amines to give phosphoramidates 13±16 in yields
of 66±75% (Table 3).
The structures of phosphates 4±9 were established by
multinuclear NMR and infrared spectroscopy and by high
resolution mass spectrometry (Table 2). The frequencies of
the P=O infrared vibrations decrease as the electronegativity
of the substituents attached to the phosphorus atom
decreases [11]. For example: (CF3CH2O)2P(O)OEt 6
(1301 cm 1)>(EtO)2P(O)OCH2CF3 (1271 cm 1)>(EtO)3-
P=O (1264 cm 1) [3].
2.3. Reactivities of alkyl bis(trifluoroethyl) phosphates
towards bromotrimethylsilane
Table 3
Experimental data for the fluoroalkyl phosphoramidatesa
Previously we showed that dialkyl tri¯uoroethyl
phosphates (RO)2P(O)OCH2CF3 reacted with bromotri-
methylsilane (TMSBr) to give the silylated esters RO(TM-
SO)P(O)OCH2CF3 and (TMSO)2P(O)OCH2CF3 (RˆMe,
Et) [3]. The mechanism was postulated as attack of the
alkoxy oxygen atom on the silicon atom of TMSBr, fol-
lowed by loss of alkyl bromide. Electronegative ¯uoroalkyl
groups on phosphorus should decrease the nucleophilicity
of the alkoxy groups in unsymmetrical phosphates, lowering
their reactivity to TMSBr. It was, therefore, no surprise that
phosphates 4 and 6 were not silylated even on re¯uxing for
several hours in chloroform.
Compound
R
R0
Yield
(%)
Boiling point
(8C/mm Hg)
Compounds of general formula (RR0N)2P(O)OCH2CF3
10
11
12
Me
Me
Et
Me
Et
70b
44/0.4
68/1
63
Et
58
82/0.06
Compounds of general formula (CF3CH2O)2P(O)NRR0
13
14
15
16
H
Me
Me
Et
68
70b
66
75
84±86/1
37/0.5
96/0.1
62/1
Me
H
Et
Et
a Prepared by addition of amines to trifluoroethyl phosphorodichlor-
idate.
b Compounds 10 and 14 were also made by DMAP-catalysed addition
of trifluoroethanol to the respective phosphoramidic chlorides in yields of
50 and 61%, respectively.

Table 4
Spectroscopic data for fluoroalkyl phosphoramidates (NMR data measured in CDCl3)
1
Compound
1H NMR d, J (Hz)
13C NMR d, J (Hz)
19F NMR d, J (Hz)
31P NMR d
IR n (cm
)
HRMS analysis
10
4.25 (2H, dq, Jˆ9, 6, OCH2),
2.67 (12H, d, Jˆ10, NCH3)
122.7 (dq, Jˆ11.2, 277, CF3),
61.9 (dq, Jˆ3, 37, OCH2),
36.1 (NCH3)
74.3 (3F, t, Jˆ8, CF3)
19.7
1460, 1288 (P=O), 1223, 1169,
1095, 1071, 992, 964, 858
Calc. C6H14F3N2O2P 234.075,
found 234.075 (error 3.7)
11
4.23 (2H, dq, Jˆ9, 7, OCH2),
3.05 (4H, dq, Jˆ10, 6, NCH2),
2.64 (6H, d, Jˆ10, NCH3),
1.13 (6H, t, Jˆ7, CH3)
123.3 (dq, Jˆ11.2, 277, CF3),
61.7 (dq, Jˆ3, 37, OCH2),
43.5 (NCH2), 32.7 (NCH3),
13.5 (CH3)
74.1 (3F, t, Jˆ8, CF3)
18.7
1655, 1458, 1419, 1383, 1346,
1288 (PˆO), 1244, 1209, 1171,
1095, 1014, 962, 937, 856
Calc. C8H18F3N2O2P 262.106,
found 262.107 (error 5.7)
12
13
14
15
4.25 (2H, dq, Jˆ9, 6, OCH2),
3.11 (8H, dq, Jˆ7, 9, NCH2),
1.11 (12H, t, Jˆ7, CH3)
123.3 (dq, Jˆ11, 277, CF3),
61.3 (dq, Jˆ3, 37, OCH2),
39.5 (NCH2), 14 (CH3)
122.5 (dq, Jˆ10, 277, CF3),
62.5 (dq, Jˆ4, 38, OCH2),
27.1 (NHCH3)
74.7 (3F, t, Jˆ8, CF3)
75.1 (6F, t, Jˆ8, CF3)
74.6 (6F, t, Jˆ8, CF3)
74.4 (6F, t, Jˆ8, CF3)
18.0
9.4
9.7
8.3
1466, 1382, 1288 (P=O), 1239,
1212, 1167, 1096, 1077, 1028,
962, 941, 832
Calc. C10H22F3N2O2P 290.137,
found 290.137 (error 0.6)
4.32 (4H, dq, Jˆ8, 9, OCH2),
3.76 (1H, br, NH), 2.6 (3H,
dd, Jˆ6, 13, NCH3)
1458, 1423, 1290 (P=O), 1252,
1174, 1078, 964, 879, 795
Calc. C5H8F6NO3P 275.015,
found 275.013 (error 5.9)
4.32 (4H, dq, Jˆ8, 9, OCH2),
2.71 (6H, d, Jˆ11, NCH3)
122.7 (dq, Jˆ10, 277, CF3),
62.9 (dq, Jˆ5, 38, OCH2),
36.4 (d, Jˆ4, NCH3)
1420, 1296 (P=O), 1258, 1174,
1110, 1074, 1008, 965, 877
Calc. C6H10F6NO3P 289.030,
found 289.029 (error 4.1)
4.32 (4H, dq, Jˆ8, 9, OCH2),
3.5 (1H, m, NH), 3.01 (2H,
m, NCH2), 1.17 (3H, dt,
Jˆ1, 7, CH3)
122.7 (dq, Jˆ10, 277, CF3),
62.9 (dq, Jˆ4, 38, OCH2),
36.5 (NCH2), 16.9 (CH3)
1456, 1423, 1288 (P=O), 1250,
1174, 1078, 964, 879, 812
Calc. C6H10F6NO3P 289.030,
found 289.029 (error 5.8)
16
4.29 (4H, dq, Jˆ8, 9, OCH2),
3.12 (4H, dq, Jˆ7, NCH2),
1.13 (6H, t, Jˆ7, CH3)
122.6 (dq, Jˆ11, 277, CF3),
62.6 (dq, Jˆ3, 38, OCH2),
39.8 (d, Jˆ5, NCH2),
74.8 (6F, t, Jˆ8, CF3)
9.0
1456, 1423, 1387,
Calc. C8H14F6NO3P 317.062,
found 317.061 (error 1.6)
1294 (P=O), 1261, 1215,
1171, 1111, 1074, 1039, 966
13.8 (d, Jˆ3, CH3)

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C.M. Timperley et al. / Journal of Fluorine Chemistry 104 (2000) 215±223
Fluoroalkyl phosphoramidates can also be synthesised
Whereas (EtO)2P(O)NMe2 gave (EtO)2P(O)Cl in 87%
yield when treated with hydrogen chloride [17], the ¯uori-
nated analogue 14 remained unchanged.
from dialkylphosphoramidic chlorides, ¯uoroalcohols and
triethylamine. Without a catalyst, the reaction is slow or
does not take place at all. However, a catalytic amount of 4-
dimethylaminopyridine (DMAP) facilitated the reaction of
chlorides 17 and 18 with tri¯uoroethanol, enabling phos-
phoramidates 10 and 14 to be isolated in modest yields.
This contrast in reactivity is mainly due to the electro-
negativity of the ¯uoroethyl groups. Other electron-with-
drawing groups have a similar effect; the substituents on
phosphorus have been placed in the sequence EtO>PhO>Cl,
according to their ability to facilitate acid hydrolysis [17].
3. Conclusion
Some simple ¯uoroalkyl phosphorochloridates have
been prepared and shown to react with alcohols (to give
phosphates) and with amines (to give phosphoramidates).
Inductive ¯uoroalkyl groups on phosphorus lower its reac-
tivity to electrophiles. Whereas, the phosphate (CF3CH2O)2-
P(O)OEt did not react with bromotrimethylsilane, the
related phosphate (EtO)2P(O)OCH2CF3 reacted to give
silylated products with retention of the ¯uoroalkyl group
[3]. Also, the phosphoramidate (CF3CH2O)2P(O)NMe2 did
not react with anhydrous hydrogen chloride, but the
un¯uorinated phosphoramidate (EtO)2P(O)NMe2 gave
diethyl phosphorochloridate [17].
Compounds 10±16 are mobile colourless liquids (Table 3)
that were fully characterised by the usual techniques
(Table 4). The phosphoramidates have particularly charac-
teristic carbon NMR spectra, the tri¯uoromethyl carbon
appearing at around d 120 as a doublet of quartets with
coupling constants of about 10 and 280 Hz, corresponding
3
1
to JCP and JCF, respectively.
2.5. Reactivities of fluoroethyl phosphoramidates towards
hydrogen chloride
Compounds of the type (EtO)2P(O)NR2 (R=H, Me, Et,
Ph) react with anhydrous hydrogen chloride to form diethyl
phosphorochloridate, (EtO)2P(O)Cl [17]. This process is
irreversible as the detached amino group is transformed
into an unreactive ammonium ion. Electronegative ¯uor-
oalkoxy groups on phosphorus lower the basicity of the
amino group, decreasing its susceptibility to acid hydro-
lysis. An extra dimethylamino group, however, diminishes
the resistance to hydrolysis. Scission of the P±N bond was
possible in diamidate 10 (an exact amount of HCl was
generated in situ from acetyl chloride and methanol), and
after 5 days, a 90% conversion to monochloride 19 had
occurred. However, on the small scale used, the latter could
not be separated from the residual starting material by
distillation.
4. Experimental details
All reagents were of commercial quality: ¯uoroalcohols
were purchased from Apollo Scienti®c Ltd (Derbyshire,
UK). Anhydrous solvents were used for reactions. Triethy-
lamine was distilled from CaH2 and stored over CaH2. NMR
spectra were obtained on a JEOL Lambda 500 instrument
(operating at 500 MHz for 1H, 125 MHz for 13C, 470 MHz
for 19F, and 202 MHz for 31P spectra) or a JEOL Lambda
300 instrument (operating at 300 MHz for H, 75 MHz for
13C, 282 MHz for 19F, and 121.5 MHz for 31P spectra) as
solutions in CDCl3, with internal reference SiMe4 for H
and 13C, external CFCl3 for 19F and external (MeO)3P (d
140 ppm) for 31P spectra. Data in Tables 2 and 4 are
recorded as follows: chemical shifts in ppm from reference
on the d scale, integration, multiplicity (sˆsinglet,
dˆdoublet, tˆtriplet, qˆquartet, mˆmultiplet and sepˆ
septet; brˆbroad), coupling constant (Hz) and assignment.
IR spectra were recorded as liquid ®lms on a Nicolet SP210
instrument using Omnic software. Reaction mixtures were
monitored by gas chromatography-mass spectrometry (GC-
MS) using a Finnigan MAT GCQ instrument with chemical
ionisation (CI) using methane as reagent gas. Molecular
weights of pure products were con®rmed with methane
positive CI data. Elemental analysis was carried out on
the largest stable fragment ion, using high resolution mass
1
1
The activating effect of an extra dimethylamino group is
also seen in the contrasting behaviour of (Me2N)2P(O)F and
Me2NP(O)F2 20 towards hydrogen chloride, the former
losing both amino groups to give Cl2P(O)F [17]. Di¯uoride
20, ®rst synthesised by Schrader [18], was made by a new
route that involved ¯uorination of N,N±dimethylphosphor-
amidic dichloride with triethylamine hydro¯uoride; it did
not react with anhydrous hydrogen chloride in ether at room
temperature (see Section 4.10).

C.M. Timperley et al. / Journal of Fluorine Chemistry 104 (2000) 215±223
221
spectrometry (HRMS) on a Micromass Autospec SQ Dou-
4.2. Synthesis of alkyl bis(fluoroalkyl) phosphates (4±9)
ble Focusing Magnetic Sector instrument. Mode: positive
ion electron impact, magnet scan m/z 400±100 (seconds/
decade), resolution 2900. Inlet: septum (1608C), 0.2 ml
introduced. Source conditions: temperature 2008C, electron
energy 70 eV, and accelerating voltage 8000 V. All reaction
mixtures were stirred magnetically. Spectroscopic data are
recorded in Tables 2 and 4.
A solution of the alcohol (0.01 mol) and triethylamine
(0.01 mol) in Et2O (10 ml) was added dropwise by cannula
to a solution of the appropriate bis(¯uoroalkyl) phosphoro-
chloridate (0.01 mol) in Et2O (25 ml) cooled to 0±58C.
After addition, the mixture was allowed to warm to room
temperature and left for 12 h. Analysis by GC-MS showed
that the desired product predominated. The precipitate was
®ltered off and the ®ltrate concentrated to an oil. Bulb-to-
bulb distillation, or fractionation using a microdistillation
apparatus, gave the title compounds as colourless mobile
liquids.
4.1. General procedure for fluoroalkyl
phosphorochloridates (1±3)
Triethylamine (0.25 or 0.5 mol) was added dropwise
to a solution of phosphorus oxychloride (0.25 mol) and
¯uoroalcohol (0.25 or 0.5 mol) in Et2O (25 ml) cooled to
0±58C. After addition, the mixture was warmed to room
temperature and re¯uxed for 2 h. The precipitate was
removed by ®ltration and the ®ltrate concentrated to a
liquid. Sometimes further triethylamine hydrochloride pre-
cipitated on standing. Filtration through a short column of
silica gel, removal of solvent, and fractionation under
reduced pressure gave the title compounds as colourless
mobile liquids.
4.3. Reaction of methyl phosphorodichloridate with
fluoroalcohols
A solution of the ¯uoroalcohol (0.14 mol) and triethyla-
mine (0.14 mol) in Et2O (100 ml) was added dropwise to a
stirred solution of methyl phosphorodichloridate (0.07 mol)
in Et2O (100 ml) cooled to 0±58C. After addition, the
mixture was allowed to warm to room temperature and left
for 12 h.
4.1.1. 2,2,2-Trifluoroethyl phosphorodichloridate (1)
Yield 36% (bp 59±618C/10 mm Hg, lit. bp 45.5±468C/
15 mm Hg [9]). 1H NMR: dˆ4.6 (2H, dq, Jˆ7 and 7.6 Hz,
OCH2). 13C NMR: dˆ121.6 (dq, Jˆ12 and 277 Hz, CF3),
65.3 (dq, Jˆ7 and 39 Hz, OCH2). 19F NMR: dˆ 73.5 (3F, t,
Jˆ7 Hz, CF3). 31P NMR: dˆ8.8. IR: nˆ1454, 1421, 1302
(P=O), 1281, 1178, 1093, 1070, 962, 866, 844, 660, 598,
567, 522 cm 1. HRMS: Calc. for C2H2Cl2F3O2P 215.912
4.3.1. With 2,2,2-trifluoroethanol
Analysis by GC-MS showed a 2:1 mixture of desired
product and tris(2,2,2-tri¯uoroethyl) phosphate. The pre-
cipitate was ®ltered off and the ®ltrate concentrated to a
mobile oil. Distillation under reduced pressure gave a liquid
(bp 378C/0.1 mm Hg) with a ratio of bis to tris substituted
phosphates 4 and 4a similar to that of the crude product.
‡
([M HF] ˆ195.906), found 195.906 (error 2).
4.3.2. With 2,2,3,3,3-pentafluoropropanol
Analysis by GC-MS showed a 4:1 mixture of desired
product and tris(2,2,3,3,3-penta¯uoropropyl) phosphate.
The precipitate was ®ltered off and the ®ltrate concentrated
to a mobile oil. Distillation under reduced pressure gave a
liquid (bp 658C/0.2 mm Hg) with a ratio of bis to tris
substituted phosphates 5 and 5a similar to that of the crude
product.
4.1.2. Bis(2,2,2-trifluoroethyl) phosphorochloridate (2)
Yield 40% (bp 61±628C/10 mm Hg, lit. bp 67±688C/
14 mm Hg [9]). 1H NMR: dˆ4.55 and 4.51 (4H, qdd,
Jˆ3.3, 7.6 and 15.3 Hz, OCH2). 13C NMR: dˆ121.8 (dq,
Jˆ11 and 277 Hz, CF3), 64.7 (dq, Jˆ6 and 34 Hz, OCH2).
19F NMR: dˆ 74.2 (6F, t, Jˆ7 Hz, CF3). 31P NMR: dˆ4.7.
IR: nˆ1456, 1423, 1377, 1301 (P=O), 1275, 1175, 1067,
963, 898, 847, 662, 587, 558, 519 cm 1. HRMS: Calc. for
4.4. Reaction of ethyl phosphorodichloridate with
fluoroalcohols
‡
C4H4ClF6O3P 279.949 ([M-HF] ˆ259.943), found
259.943 (error 1.9).
A solution of the ¯uoroalcohol (0.12 mol) and triethyla-
mine (0.12 mol) in Et2O (100 ml) was added dropwise to a
solution of ethyl phosphorodichloridate (0.06 mol) in Et2O
(100 ml) cooled to 0±58C. After addition, the mixture was
allowed to warm to room temperature and left for 12 h.
Analysis by GC-MS showed 95% conversion to the desired
product. The precipitate was ®ltered off and the ®ltrate
concentrated to an oil. Fractionation under reduced pressure
gave the following as colourless liquids:
4.1.3. Bis(2,2,3,3,3-pentafluoropropyl)
phosphorochloridate (3)
1
Yield 45% (bp 74±768C/10 mm Hg). H NMR: dˆ4.61
(4H, broad m, OCH2). 13C NMR: dˆ117.2 (m, CF3), 111.3
(m, CF2), 63.8 (m, OCH2). 19F NMR: dˆ 123.5 (4F, m,
CF2) and 82.8 (6F, m, CF3). 31P NMR: dˆ4.6. IR:
nˆ1458, 1377, 1356, 1306 (P=O), 1271, 1205, 1163,
1111, 1066, 1030, 937, 893, 843, 795, 721, 660,
623 cm 1. HRMS: Calc. for C6H4ClF10O3P 379.943
Ethyl bis(2,2,2-tri¯uoroethyl) phosphate (6): bp 378C/
0.01 mm Hg (yield 52%).
‡
([M HF] ˆ359.937), found 359.936 (error 1.7).

222
C.M. Timperley et al. / Journal of Fluorine Chemistry 104 (2000) 215±223
Ethyl bis(2,2,3,3,3-penta¯uoropropyl) phosphate (7): bp
45±468C/0.04 mm Hg (yield 35%).
Analysis by GC-MS showed the mixture to comprise
96% desired product. The precipitate was ®ltered off and
the ®ltrate concentrated to an oil. Fractionation under
reduced pressure gave the title compound as a colourless
liquid (10.9 g, 61%); bp 388C/0.5 mmHg.
4.5. Attempted reaction of alkyl bis(trifluoroalkyl)
phosphates with bromotrimethylsilane
Bromotrimethylsilane (1.8 mmol) was added by syringe
to a solution of methyl or ethyl bis(2,2,2-¯uoroethyl) phos-
phate 4 or 6 (1.8 mmol) in CHCl3 (20 ml) under argon at
room temperature. After addition, the mixture was left for
1 h. Analysis by GC-MS indicated that no reaction had
taken place. Re¯uxing for several hours and sampling by
GC-MS showed only the presence of starting phosphate.
4.9. N,N±Dimethylphosphoramidic difluoride (20)
Triethylamine (4.04 g, 0.04 mol) was added to a solution
of triethylamine trihydro¯uoride (3.22 g, 0.02 mol) in ether
(250 ml) in a 250 ml three-neck ¯ask. The reaction was
exothermic and triethylamine hydro¯uoride precipitated as
a solid. It was broken up with a glass rod to give a ®ne
suspension upon stirring. The centre neck was ®tted with a
pressure equalising dropping funnel with gas bubbler. The
outer necks were ®tted with septa, one of which was pierced
by an argon entry needle. To the funnel Me2NP(O)Cl2
(4.86 g, 0.03 mol) in Et2O (75 ml) was added. The ¯ask
was cooled to 08C and the phosphoramidic dichloride added
dropwise with stirring over 40 min. Stirring was continued
for 1 h at 08C and a further 2 h at room temperature. The
reaction mixture was left to stand under argon for 12 h. The
clear liquid was decanted from the mixture through a thin
layer of Celite1 in a sinter funnel. Ether (80 ml) was added
to the residue, which was shaken, and the liquid (and some
solid) was decanted into the ®lter and this procedure
repeated about ®ve times until all the solid was in the
funnel. The precipitate was rinsed with more Et2O and
the ®ltrate concentrated on a rotary evaporator (2.4 g crude
product). The above procedure was repeated and the crude
products combined and distilled at reduced pressure in a
micro-distillation apparatus with a single receiver ¯ask
which was cooled in a dry ice±acetone slush bath. The title
compound was isolated as a colourless mobile liquid
(3.28 g, 42%); bp 238C/20 mmHg (oil pump with an adjus-
table air bleed; lit. 288C/10 mm Hg [18]). 1H NMR: dˆ2.74
(6H, dt, Jˆ11 and 1.8 Hz, NCH3). 13C NMR: dˆ32.6
(JCPˆ5 Hz, NCH3). 19F NMR: dˆ 79.7 (2F, d, JPFˆ
999 Hz, P-F). 31P NMR: dˆ 4.5 (t, JPFˆ999 Hz).
4.6. General procedure for 2,2,2-trifluoroethyl N,N,N0,N0-
tetraalkylphosphorodiamidates (10±12)
A solution of dialkylamine (0.16 mol) in Et2O (10 ml)
was slowly added dropwise by cannula to a solution of
2,2,2-tri¯uoroethyl phosphorodichloridate (0.04 mol) in
Et2O (15 ml) cooled to 0±58C. After addition, the mixture
was allowed to warm to room temperature and left for 5
days. Analysis by GC-MS showed 90% conversion to the
desired product. The precipitate was ®ltered off and the
®ltrate concentrated to an oil. Fractionation under reduced
pressure gave the pure title compounds.
4.7. 2,2,2-Trifluoroethyl N,N,N0,N0-
tetramethylphosphorodiamidate (10)
A solution of 2,2,2-tri¯uoroethanol (13 g, 0.13 mol) and
triethylamine (13.1 g, 0.13 mol) in Et2O (50 ml) was added
dropwise to a solution of N,N,N0,N0±tetramethylphosphor-
odiamidic chloride (22.1 g, 0.13 mol) in Et2O (50 ml)
cooled to 0±58C. After addition, the mixture was allowed
to warm to room temperature and then re¯uxed for 2 h.
Analysis by GC-MS showed that no reaction had taken
place. 4-Dimethylaminopyridine (0.8 g, 6.5 mmol) was
added and mixture re¯uxed for another 26 h. Analysis by
GC-MS showed that product predominated by 88%. The
precipitate was ®ltered off and the ®ltrate concentrated to an
oil. Fractionation under reduced pressure gave the title
compound as a colourless liquid (15.2 g, 50%); bp 458C/
0.4 mm Hg.
4.10. Reactivities of fluorinated phosphoramidates
towards hydrogen chloride
A solution of methanol (0.55 g, 0.017 mol) and acetyl
chloride (1.33 g, 0.017 mol) in Et2O (10 ml) was added
dropwise by cannula to a solution of ¯uorinated phosphor-
amidate (0.009 mol) in Et2O (25 ml) cooled to 0±58C. After
addition, the mixture was allowed to warm to room tem-
perature and left for 5 days. An aliquot was analysed by GC-
MS. With (Me2N)2P(O)OCH2CF3 10, a 90% conversion to
chloride 19 had taken place. The precipitate was ®ltered off
and the ®ltrate concentrated to an oil. Bulb-to-bulb distilla-
tion gave a mixture of compounds 10 and 19 in a 3:1 ratio as
colourless liquid (1.6 g); bp 308C/0.1 mm Hg. If repeated
on a larger scale, a better fractionation might be possible,
perhaps allowing isolation of a purer chloridate. No reaction
4.8. Bis(2,2,2-trifluorethyl) N,N-dimethylphosphoramidate
(14)
2,2,2-Tri¯uoroethanol (12 g, 0.12 mol) and triethylamine
(12.1 g, 0.12 mol) in Et2O (50 ml) was added dropwise to a
solution of N,N±dimethylphosphoramidic dichloride (9.7 g,
0.06 mol) in Et2O (50 ml) cooled to 0±58C. After addition,
the mixture was re¯uxed for 30 h. Analysis by GC-MS
showed 64% desired product and 36% mono-substituted
intermediate. 4-Dimethylaminopyridine (1.1 g, 9.3 mmol)
was added and the mixture re¯uxed for a further 8 h.

C.M. Timperley et al. / Journal of Fluorine Chemistry 104 (2000) 215±223
223
[4] G.M. Kosolapoff, Organophosphorus Compounds, London, Wiley,
1950, Chapter 9, p. 211.
occurred with (CF3CH2O)2P(O)NMe2 14 or Me2NP(O)F2
20.
[5] A.J. Elliott, in: M. Howe-Grant (Ed.), Fluorine Chemistry: A
Comprehensive Treatment, Wiley, Chichester, 1995, p. 281.
[6] I.L. Knunyants, O.V. Kil'dasheva, E. Bykovskaya, Zh. Obshch.
Khim. (Engl. transl.) 19 (1949) 93.
Acknowledgements
[7] M.I. Kabachnik, E.I. Golubeva, D.M. Paikin, M.P. Shabanova, N.M.
Gamper, L.F. Efimova, Zh. Obshch. Khim. (Engl. transl.) 29 (1959)
1657.
Many thanks to Alison Bussey, Ella Greenaway and Steve
Marriott for their excellent technical support. We also wish
to thank DERA Haslar (Environmental Sciences) for fund-
ing the work.
[8] L.F. Audrieth, A.D.F. Toy, J. Am. Chem. Soc. 63 (1941) 2117.
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