Fluorinated phosphorus compounds: Part 5. The boiling points of fluoroalkyl phosphoryl compounds

Article abstract of DOI:10.1016/S0022-1139(01)00362-1

The relationship between structure and boiling point for several classes of phosphoryl compounds having fluorinated or hydrocarbon ester groups is discussed, i.e. phosphoramidates (R₂N)₂P(O)OCH₂R_F and (R_FCH₂O)₂P(O)NR₂, phosphates (RO)₂P(O)OR_F, (R_FCH₂O)₂P(O)OR, (R_FO)₃P=O and (R_FCH₂O)₂P(O)OCH₂R′ _F, and phosphonates (R_FO)₂P(O)R, where R= alkyl and R_F= fluoroalkyl. Fluorination generally produces compounds of similar or lower boiling point than the unfluorinated parent compounds. A key factor governing the boiling point of a fluorinated phosphoryl compound relative to its hydrocarbon analogue is not its molecular weight, but the position and number of fluorine atoms in the ester linkage(s). Molecules with an umbrella of fluorine atoms repel each other, leading to low intermolecular forces: the boiling points of (C₃F₇CH₂O)₃P=O and (C₃H₇CH₂O)₃P=O are close despite a molecular weight difference of 378. Molecules with protons capable of intermolecular hydrogen-fluorine bonding (i.e. those containing -NHR or -CF₂H groups) have higher boiling points than those without, due to attractive forces in the liquid state. Synthetic procedures for four unfluorinated phosphates - (MeO)₂P(O)O-i-Pr, (MeO)₂P(O)O-n-Bu, (EtO)₂P(O)O-i-Pr and (s-BuO)₃P=O are outlined.

Full text of DOI:10.1016/S0022-1139(01)00362-1

Journal of Fluorine Chemistry 109 )2001ꢀ 103±111
Fluorinated phosphorus compounds
Part 5. The boiling points of ¯uoroalkyl phosphoryl compounds
*
Christopher M. Timperley , Matthew J. Waters
Defence Science and Technology Laboratory, Chemical and Biological Defence Sector, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK
Received 22 December 2000; accepted 2 February 2001
Abstract
The relationship between structure and boiling point for several classes of phosphoryl compounds having ¯uorinated or hydrocarbon ester
groups is discussed, i.e. phosphoramidates )R Nꢀ P)OꢀOCH R and )R CH Oꢀ P)OꢀNR , phosphates )ROꢀ P)OꢀOR , )R CH Oꢀ P)OꢀOR,
2
2
2
F
F
2
2
2
2
F
F
2
2
0
)
R
F
Oꢀ
produces compounds of similar or lower boiling point than the un¯uorinated parent compounds. A key factor governing the boiling point of a
uorinated phosphoryl compound relative to its hydrocarbon analogue is not its molecular weight, but the position and number of ¯uorine
atoms in the ester linkage)sꢀ. Molecules with an umbrella of ¯uorine atoms repel each other, leading to low intermolecular forces: the boiling
points of )C CH Oꢀ P=O and )C CH Oꢀ P=O are close despite a molecular weight difference of 378. Molecules with protons capable of
intermolecular hydrogen-¯uorine bonding )i.e. those containing ±NHR or ±CF H groupsꢀ have higher boiling points than those without, due
to attractive forces in the liquid state. Synthetic procedures for four un¯uorinated phosphates Ð )MeOꢀ P)OꢀO-i-Pr, )MeOꢀ P)OꢀO-n-Bu,
3
P=O and )R
F
CH
2
Oꢀ
2
P)OꢀOCH
2
R , and phosphonates )R
F
Oꢀ
2
P)OꢀR, where Rˆ alkyl and R
F
ˆ ¯uoroalkyl. Fluorination generally
F
¯
F
3 7
2
3
H
3 7
2
3
2
2
2
)
2 3
EtOꢀ P)OꢀO-i-Pr and )s-BuOꢀ P=O are outlined. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Bis)¯uoroalkylꢀ alkyl phosphates; Bis)¯uoroalkylꢀ alkylphosphonates; Bis)¯uoroalkylꢀ N,N-dialkylphosphoramidates; Fluoroalkyl phosphates;
0
0
Fluoroalkyl N,N,N ,N -tetraalkylphosphorodiamidates
1
. Introduction
much greater molecular weights [2]. Such trends re¯ect
the extremely low intermolecular interactions in per-
¯uoro-compounds. In most series of ¯uorinated compounds,
the relationship between structure and boiling point is poorly
established. Many ¯uoroalkyl phosphoryl compounds have
been made in our laboratories to date [3±6] and, as most of
their hydrocarbon counterparts were known, it was of inter-
est to see how their boiling points compared. Classes of
compounds considered were phosphoramidates A and B,
The unusual physical properties of organic molecules
containing ¯uorine have fascinated chemists for years. An
early surprise was the discovery that the boiling points of
linear alkanes and per¯uoroalkanes tracked each other
closely despite large differences in molecular weight [1].
Branching, which tends to lower the boiling points of
hydrocarbons, often has little effect on the boiling points
of per¯uorocarbons. Comparison of the boiling points of
some isomers of pentane and per¯uoropentane illustrates
these generalisations [2].
1
phosphates C±F and phosphonates G )Fig. 1ꢀ. In the case of
phosphates of structure F, a few un¯uorinated analogues
required preparation )their synthesis is described later Ð see
Section 3ꢀ.
The aim of this study is to examine how replacement
of protons with ¯uorine atoms in¯uences boiling point.
1
Organic phosphorus compounds are named after the corresponding
parent acids. Most compounds described in this paper are derivatives of
phosphoric acid )HOꢀ P=O, except for compounds of type G which are
3
Per¯uorinated ethers and amines also boil at much lower
temperatures than hydrocarbon analogues despite their
derivatives of alkylphosphonic acids )HOꢀ
2
P)OꢀR. They are named as
0
0
follows: A, fluoroalkyl N,N,N ,N -tetraalkylphosphorodiamidates; B, bis)-
fluoroalkylꢀ N,N-dialkylphosphoramidates; C, dialkyl fluoroalkyl phos-
phates; D, bis)fluoroalkylꢀ alkyl phosphates; E, tris)fluoroalkylꢀ
phosphates; F, bis)fluoroalkylꢀ fluoroalkyl phosphates; and G bis)fluor-
oalkylꢀ alkylphosphonates.
*
Corresponding author. Tel.: ‡44-1980-613566;
fax: ‡44-1980-613371.
E-mail address: cmtimperley@dera.gov.uk )C.M. Timperleyꢀ.
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ) 0 1 ꢀ 0 0 3 6 2 - 1

104
C.M. Timperley, M.J. Waters / Journal of Fluorine Chemistry 109 ꢀ2001) 103±111
much when Me N is replaced by EtMeN, but increases
2
appreciably when it is replaced by Et N. For example,
2
compare 1f with 2f and 3f.
Hydrocarbon compounds of structure B contain one
amino group and have boiling points close to those of the
¯
CH CH O± group with a CF CH O± group does not affect
uorinated analogues )Table 2ꢀ. Replacement of a
Fig. 1. Compounds investigated )Rˆ alkyl and R ˆ fluoroalkylꢀ.
F
3
2
3
2
the boiling point much, despite the weight difference of 54
mass units. Compounds with alkylamino groups boil 50±
Discussion will focus on the relationship of structure to
boiling point for each of the classes of compounds in Fig. 1.
Data is presented in seven tables )the suf®xes f and h after
the compound numbers indicate ¯uorocarbon or hydrocar-
bon ester groupsꢀ. As boiling points were recorded at
different pressures, values at atmospheric pressure were
estimated using a pressure±temperature nomograph. When
close boiling points for un¯uorinated phosphorus com-
pounds appeared in the literature, the average was taken.
908C higher than those with dialkylamino groups )compare
4f with 5f and 6f with 7fꢀ. The higher boiling points of the
former can be ascribed to intermolecular hydrogen bonding
between the amino proton and the ¯uoro-ester groups of
associated molecules.
2
. Boiling point comparisons
2
.1. Phosphoramidates A and B
Hydrocarbon compounds of structure A contain two
amino groups and boil at similar or lower temperatures than
their ¯uoro analogues )Table 1ꢀ. Increasing the size of the
dialkylamino group raises the boiling point. In hydrocarbon
and ¯uorocarbon pairs, the boiling point does not change
Table 1
0
Data for phosphorus amides of structure )RR Nꢀ
2
2
P)OꢀOCH R
F
)class Aꢀ
0
Compound
R
R
R
F
bp )8C/mmHgꢀ
bp )8C/760 mmHgꢀ
Reference
1
1
2
2
3
3
f
Me
Me
Me
Me
Et
Me
Me
Et
CF
CH
3
44/0.4
220
220
235
225
305
255
[4]
[7]
[4]
[8]
[4]
[9]
h
f
3
3
3
103±104/18
68/1
CF
3
h
f
Et
CH
56±58/1
82/0.06
79±80/0.8
Et
CF
3
h
Et
Et
CH
Table 2
0
Data for phosphorus amides of structure RR NP)Oꢀ)OCH
2
F
R ꢀ
2
)class Bꢀ
0
Compound
R
R
R
F
bp )8C/mmHgꢀ
bp )8C/760 mmHgꢀ
Reference
4
4
5
5
6
6
7
7
f
Me
Me
Me
Me
Et
H
CF
CH
3
84±86/1
135/17, 130/15
37/0.5
260
260
210
210
320
315
230
230
[4]
h
f
H
3
3
3
3
[10,11]
[4]
Me
Me
H
CF
3
h
f
CH
84/12
96/0.1
[12]
[4]
CF
3
h
f
Et
H
CH
80/0.03
[13]
[4]
Et
Et
Et
CF
3
62/1
h
Et
CH
91/6, 101/13
[7,12]

C.M. Timperley, M.J. Waters / Journal of Fluorine Chemistry 109 ꢀ2001) 103±111
105
Table 3
Data for phosphorus esters of structure )ROꢀ
2
F
P)OꢀOR )class Cꢀ
Compound
R
R
F
bp )8C/mmHgꢀ
bp )8C/760 mmHgꢀ
Reference
8
8
9
9
f
Me
Me
Me
Me
Me
Me
Me
Me
Et
CH
CH
CH
CH
2
2
2
2
CF
CH
3
54/1.8
112/41
61/1
205
[3]
a
h
f
3
205
[14]
[3]
C
C
2
F
5
230
240
180
290
250
305
215
h
2
H
5
116/15
50/6
[15]
[3]
1
1
1
1
1
1
1
1
1
1
1
1
0f
CH)CF
3 2
ꢀ
0h
1f
CH)CH
3
ꢀ
2
61/0.03
42/0.06
70/0.02
[16]
[3]
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
C
C
3
F
7
1h
2f
3
H
7
[16]
[3]
b
CF
CH
3
90/13
a
2h
3f
Et
3
±
215
[16]
[3]
Et
C
C
2
F
5
90/12
210
240
235
215
220
245
3h
4f
Et
2
H
5
130/20, 96±97/6
56/0.5
[15,17]
[3]
Et
CH)CF
3 2
ꢀ
4h
5f
Et
CH)CH
3
ꢀ
2
91/11
[18]
[3]
Et
CH
CH
2
C
C
3
F
7
88/8
5h
Et
2
3
H
7
81/1, 123/15
[17,19]
a
This value is not extrapolated.
b
Original figure 60±668C/0.05 mmHg [3] is too high Ð a resynthesised sample of 98%‡ purity )by multinuclear NMRꢀ had the boiling point shown in
the table.
2
.2. Phosphates C
2.3. Phosphates D
Dialkyl ¯uoroalkyl phosphates of structure C contain one
uoro-ester group and have similar or lower boiling points
Bis)¯uoroalkylꢀ alkyl phosphates of structure D contain
two ¯uoro-ester groups and have boiling points 10±408C
higher than their hydrocarbon analogues )Table 4ꢀ. For
example, compare 16f with 16h.
¯
than their un¯uorinated analogues )Table 3ꢀ. For example,
compare 8f with 8h and 15f with 15h.
The higher boiling points of the ¯uoro compounds might
arise from increased attractions between the ¯uoro-ester
groups of one molecule and the electron-de®cient alkoxy
groups of another. The alkoxy groups in molecules of
structure D are unusually polarised: the methoxy group in
compounds )R CH Oꢀ P)OꢀOMe, where R is CF or C F ,
F
2
2
F
3
2 5
can be displaced under mild conditions [4].
Table 4
Data for phosphorus esters of structure ROP)Oꢀ)OCH
2
F 2
R ꢀ )class Dꢀ
Compound
R
R
F
bp )8C/mmHgꢀ
bp )8C/760 mmHgꢀ
Reference
1
1
1
1
1
1
1
1
6f
Me
Me
Et
CF
3
42/0.1
245
[4]
a
6h
7f
CH
3
3
3
3
101/24, 208
37/0.01
208
250
[18,20]
[4]
CF
3
a
2h
8f
Et
CH
±
215
[21]
[4]
n-Pr
n-Pr
i-Pr
i-Pr
CF
3
45/0.015
130/20, 96±97/6
37/0.015
46/0.03
270
240
260
270
3h
9f
CH
[15,17]
[4]
CF
3
9h
CH
[16]
a
This value is not extrapolated.

106
C.M. Timperley, M.J. Waters / Journal of Fluorine Chemistry 109 ꢀ2001) 103±111
Table 5
Data for phosphorus esters of structure )R
F 3
Oꢀ P=O )class Eꢀ
Compound
R
F
bp )8C/mmHgꢀ
bp )8C/760 mmHgꢀ
Reference
2
1
2
2
2
2
2
2
2
2
2
2
0f
CH
CH
CH
CH
CH
2
2
2
2
2
CF
3
40/0.6
±
210
215
[6]
a
2h
1f
CH
3
[22]
[6]
C
C
2
F
5
64/0.9
±
235
a
1h
2f
2
H
5
252
[22]
[6]
)CF
2
ꢀ
2
H
102/0.015
248C )mpꢀ
49/0.02
84/5
360
±
3f
CH)CF
3
ꢀ
2
[6]
4f
CH)CH
CH)CH
2
3
Fꢀ
2
275
225
275
[6]
4h
5f
ꢀ
2
[23]
[6]
CH
CH
2
C
C
3
F
7
63/0.08
±
a
5h
6f
2
3
H
7
289
[22,24]
[6]
CH)CH
CH)CH
3
ꢀC
ꢀC
2
F
5
62/0.8
80/0.015
230
325
6h
3
2
H
5
[16]
a
This value is not extrapolated.
2
.4. Phosphates E
Symmetrical tris)¯uoroalkylꢀ phosphates of structure E
Tris)hepta¯uorobutylꢀ phosphate 25f has an extrapolated
boiling point lower than that of tributyl phosphate 25h
despite a molecular weight difference of 378 mass units!
contain three identical ¯uoro-ester groups and have boiling
points determined by the number and position of the ¯uorine
atoms. Compounds with terminal per¯uoroalkyl groups boil
slightly lower than their un¯uorinated counterparts despite
large differences in molecular weight )Table 5ꢀ. For exam-
ple, compare 20f with 12h and 21f with 21h.
2.5. Phosphates F
Unsymmetrical tris)¯uoroalkylꢀ phosphates of structure F
contain two different ¯uoro-ester groups. Like the symme-
trical phosphates, they boil at similar or lower temperatures
than their hydrocarbon counterparts )Table 6ꢀ. Three ¯uor-
oalkyl groups around the phosphoryl core P=O gives mole-
cules shielded by an umbrella of ¯uorine atoms. Electronic
repulsion between the molecules gives rise to low inter-
molecular forces and accounts for their low boiling points;
compare, for example, 28f with 13h. This principle also
Table 6
0
Data for phosphorus esters of structure )R
F
CH
2
Oꢀ
2 2
P)OꢀOCH R
)class Fꢀ
F
0
Compound
R
F
R
F
bp )8C/mmHgꢀ
bp )8C/760 mmHgꢀ
Reference
2
2
1
2
2
3
3
3
3
2
3
3
3
3
7f
CF
CF
3
)CF
2
ꢀ
2
H
100/10
82/10
225
205
240
210
240
225
275
265
235
[6]
8f
3
C
2
C
2
C
3
C
3
F
5
[6]
3h
9f
CH
3
H
5
7
130/20, [15]
85/10
[15,18]
[6]
CF
3
F
7
9h
0f
CH
3
H
85/4, 123/15
100/10
124/5
[18,19]
[6]
C
2
F
5
CF
CF
3
1f
)CF
2
ꢀ
2
H
3
[6]
1h
2f
C
C
C
C
C
C
C
2
2
2
2
2
3
3
H
5
CH
)CF
3
145/20
94/5
[15]
[6]
F
5
2 2
ꢀ H
a
1h
3f
H
5
5
7
C
2
C
3
C
3
H
5
±
252
[22]
[6]
F
5
F
7
104/10
60/0.02
100/1
230
295
280
245
3h
4f
H
H
7
[16]
[6]
F
7
CF
CH
3
4h
H
3
95±96/3±4
[25]
a
This value is not extraploated.

C.M. Timperley, M.J. Waters / Journal of Fluorine Chemistry 109 ꢀ2001) 103±111
107
operates when ¯uoroalkyl groups are bound directly to
the phosphoryl core; tris)tri¯uoromethylꢀphosphine oxide
much higher temperatures than those with penta¯uoropropyl
groups ±OCH C F , presumably because the o-proton of
2
2 5
)
pressure [26], yet its un¯uorinated analogue, trimethylpho-
CF ꢀ P=O is a liquid that boils at 248C at atmospheric
the former can participate in intermolecular hydrogen-¯uor-
ine bonding.
3
3
sphine oxide )CH ꢀ P=O is a solid that melts at 1408C.
3
3
2.6. Phosphonates G
Bis)¯uoroalkylꢀ alkylphosphonates of structure G follow
similar boiling point trends as the tris)¯uoroalkylꢀ phos-
phates of structures E and F )Table 7ꢀ; they generally boil at
lower temperatures than their hydrocarbon counterparts.
Again an umbrella of ¯uorine atoms depresses the boiling
point. Branched ¯uoro-ester groups in bis)hexa¯uoroisopro-
pylꢀ alkylphosphonates give rise to much lower forces
of attraction than present in di-isopropyl analogues )the
Symmetric and unsymmetric tris)¯uoroalkylꢀ phosphates
containing the tetra¯uoropropyl group ±CH )CF ꢀ H boil at
2
2 2
Table 7
F 2
Data for phosphorus esters of structure RP)Oꢀ)OR ꢀ )class Gꢀ
Compound
R
R
F
bp )8C/mmHgꢀ
bp )8C/760 mmHgꢀ
Reference
Dialkyl methylphosphonates
3
3
3
3
3
3
3
3
3
5f
Me
Me
Me
Me
Me
Me
Me
Me
Me
CH
CH
CH
CH
CH
2
2
2
2
2
CF
CH
3
55/4 )mp 228Cꢀ
64/2
195
215
205
350
225
180
210
315
260
[5]
5h
6f
3
[27]
[5]
C
2
F
5
45/1 )mp 158Cꢀ
97/0.015
7f
)CF
2
ꢀ
2
H
H
H
H
[5]
7h
8f
C
2
H
5
94/9
[28]
[5]
CH)CF
CH)CH
3
ꢀ
2
38/2.5
8h
9f
3
ꢀ
2
66/3
[27]
[5]
CH
CH
2
C
C
3
F
7
73/0.02 )mp 208Cꢀ
86±91/1.5
9h
2
3
H
7
[29]
Dialkyl ethylphosphonates
4
4
4
4
4
4
4
4
4
0f
Et
Et
Et
Et
Et
Et
Et
Et
Et
CH
CH
CH
CH
CH
2
2
2
2
2
CF
CH
3
59/4
62/2
200
210
230
355
240
235
240
315
265
[5]
0h
1f
3
[27]
[5]
C
2
F
5
35/0.1 )mp 198Cꢀ
98/0.015
48/0.2
2f
)CF
2
ꢀ
2
[5]
2h
3f
C
2
H
5
[30]
[5]
CH)CF
CH)CH
3
ꢀ
2
41/0.15
54/0.2
3h
4f
3
ꢀ
2
[16]
[5]
CH
CH
2
C
C
3
F
7
73/0.015
138/17
4h
2
3
H
7
[31]
Dialkyl propylphosphonates
4
4
4
4
4
4
4
4
4
5f
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
CH
CH
CH
CH
CH
2
2
2
2
2
CF
CH
3
47/1
210
220
225
350
305
215
290
325
345
[5]
5h
6f
3
53/0.8
49/0.5
[16]
[5]
C
2
F
5
7f
)CF
2
ꢀ
2
95/0.015
76/0.04
34/0.3
[5]
7h
8f
C
2
H
5
[16]
[5]
CH)CF
CH)CH
3
ꢀ
2
8h
9f
3
ꢀ
2
53/0.01
80/0.015
96/0.025
[16]
[5]
CH
CH
2
C
C
3
F
7
9h
2
3
H
7
[16]
Dialkyl isopropylphosphonates
5
5
5
5
5
5
5
5
5
0f
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
CH
CH
CH
CH
CH
2
2
2
2
2
CF
CH
3
57/0.04
68/4
64/3
200
210
210
340
300
215
270
310
320
[5]
0h
1f
3
[16]
[5]
C
2
F
5
2f
)CF
2
ꢀ
2
91/0.015
69/0.03
46/0.8
65/0.1
71/0.02
74/0.01
[5]
2h
3f
C
2
H
5
[16]
[5]
CH)CF
CH)CH
3
ꢀ
2
3h
4f
3
ꢀ
2
[16]
[5]
CH
CH
2
C
C
3
F
7
4h
2
3
H
7
[16]

108
C.M. Timperley, M.J. Waters / Journal of Fluorine Chemistry 109 ꢀ2001) 103±111
molecular weight difference between the ¯uorinated and
un¯uorinated compounds is 216 mass unitsꢀ.
Treatment of dimethyl phosphorochloridate with isopro-
panol under analogous conditions gave, in addition to
dimethyl isopropyl phosphate 10h, a mixture of pyropho-
sphates )from attack of the phosphate on the starting
phosphorochloridate and loss of isopropyl or methyl chlor-
ideꢀ. The pyrophosphate ratios, determined by GC±MS,
re¯ect the ease of dealkylation of the methoxy group of
the phosphonium intermediate by chloride ion )the isopro-
poxy group is less vulnerable to dealkylationꢀ. No attempt
was made to separate the desired phosphate from the
mixture.
Bis)¯uoroalkylꢀ alkylphosphonates containing the tetra-
uoropropyl group ±CH )CF ꢀ H are exceptional as they
2 2 2
¯
boil at much higher temperatures than those with penta-
uoropropyl or propyl groups; cf. tris)¯uoroalkylꢀ phos-
phates of structures E and F )see Section 2.5ꢀ.
¯
3
. Synthetic work
Compounds required to complete the boiling point tables
were dimethyl isopropyl phosphate 10h, dimethyl butyl
phosphate 11h, diethyl isopropyl phosphate 14h and tri)s-
butylꢀ phosphate 26h.
A cleaner reaction ensued between diethyl phosphoro-
chloridate and isopropanol. A catalytic amount of 4-
dimethylaminopyridine )DMAPꢀ was used to accelerate
the otherwise sluggish addition and, after distillation, phos-
phate 14h could be isolated in low yield.
A simple method for the preparation of alkyl phosphoro-
chloridates consists of the alcoholysis of phosphorus oxy-
chloride; the hydrogen atom of the hydroxyl and the chlorine
of the phosphorus compound are removed as hydrogen
chloride. The formation of either the primary or the sec-
ondary derivatives depends upon the relative proportions of
the reagents and the reactivity of the alcohol. Slow dropwise
addition of isopropanol or butanol and triethylamine to an
excess of phosphorus oxychloride with cooling allowed the
It can be concluded that the easiest way to make dialkyl alkyl
phosphates is to put the largest alkoxy group on phosphorus
first )to give an alkyl phosphorodichloridateꢀ and then
introduce the smaller alkoxy groups. The inverse sequence,
i.e. alcoholysis of the dialkyl phosphorochloridate, requires
harsher conditions.
The action of three molar equivalents of s-butanol and
triethylamine on phosphorus oxychloride in the presence
of DMAP gave only di-s-butyl phosphorochloridate
2
phosphorodichloridates to be isolated in good yield. Metha-
nolysis of these in the presence of triethylamine furnished
phosphates 10h and 11h.
)
s-BuOꢀ P)OꢀCl even on prolonged re¯ux in ether. Work-
2
up was carried out in the usual way but the crude product
underwent decomposition on attempted distillation. The
poor reactivity of di-s-butyl phosphorochloridate necessi-
tates harsher conditions for forcing the third group onto
phosphorus. Slightly more than three molar equivalents of
sodium s-butoxide in tetrahydrofuran resulted in complete
displacement of chloride from phosphorus oxychloride
)shown by GC±MS analysisꢀ. Although, the required
phosphate 26h decomposed on vacuum distillation, a small
amount could be isolated and characterised. It contains
2
Dichloridates Cl
2
P)OꢀOR where R ˆ i-Pr or n-Bu have been made in
yields of 40 or 75%, respectively by the alcoholysis of pyrophosphate
Cl P)OꢀOP)OꢀCl
between À30 and 08C [32]. Isopropyl phosphorodi-
chloridate Cl P)OꢀO-i-Pr has been prepared in 60% yield by mixing
2
2
2
phosphorus oxychloride with isopropanol, with removal of HCl after 2 h
by bubbling a stream of dry nitrogen through the solution [33].

C.M. Timperley, M.J. Waters / Journal of Fluorine Chemistry 109 ꢀ2001) 103±111
109
three chiral groups and exists as a statistically correct 3:1
mixture of RRR/SSS and RSS/SRR diastereoisomers as
determined by phosphorus NMR spectroscopy )see experi-
mental Section 4.4ꢀ.
introduced. Source conditions: temperature 2008C, electron
energy 70 eV, and accelerating voltage 8000 V.
4.1. General procedure for alkyl phosphorodichloridates
A solution of the appropriate alcohol )0.04 molꢀ and
triethylamine )0.04 molꢀ in ether )50 mlꢀ was added drop-
wise to a stirred solution of phosphorus oxychloride
)0.06 molꢀ in ether )75 mlꢀ cooled to 0±58C. After addition
the mixture was allowed to warm to room temperature and
left for 14 h. The precipitate was removed by ®ltration and
the ®ltrate concentrated to give a liquid. This was distilled
under reduced pressure to give the dichloridate as colourless
liquid.
Dipropyl butyl phosphate 33h, the last of the missing
compounds, was isolated in good yield from the reaction of
butyl phosphorodichloridate with propanol and triethyla-
mine.
4.1.1. Isopropyl phosphorodichloridate
Yield 61% and purity 99% by phosphorus NMR analysis
)bp 408C/4 mmHg, lit. bp 608C/12 mmHg [32] and 64±
668C/14 mmHg [33]ꢀ. This material discoloured on standing
for several days in a refrigerator and was best used imme-
1
The analogue, diethyl butyl phosphate )EtOꢀ P)OꢀOn-Bu
2
diately for phosphate synthesis. H NMR d ˆ 5:04 )1H,
was produced similarly by Gerrard by the addition of the
same dichloridate to an ethereal solution of ethanol and
pyridine [19].
dsep, J ˆ 11:2 and 6.2 Hz, OCHꢀ, 1.49 )6H, dd, J ˆ 1 and
1
3
31
6.2 Hz, CH
ꢀ. C NMR d ˆ 79:6 )OCHꢀ, 23.2 )CH
ꢀ.
3
P
3
NMR d ˆ 4:7. IR )®lmꢀ n ˆ 1466, 1390, 1381, 1304 )P=Oꢀ,
1
5
182, 1146, 1097, 1012, 991, 918, 893, 737, 598, 577,
19 cm . HRMS calculated C H Cl O P 175.956. The
À1
3
7
2 2
4
. Experimental details
compound did not give a useful mass spectrum.
All reagents were of commercial quality. DMAP refers to
-dimethylaminopyridine. Anhydrous solvents were used
4.1.2. Butyl phosphorodichloridate
Yield 54% and purity 99% by phosphorus NMR analysis
)bp 508C/1.5 mmHg, lit. bp 858C/13 mmHg [19]ꢀ. H NMR
4
1
for reactions; tetrahydrofuran was distilled from sodium
wire/benzophenone. Triethylamine was distilled from
CaH and stored over CaH . NMR spectra were obtained
d ˆ 4:35 )2H, dt, J ˆ 10 and 6.4 Hz, OCH ꢀ, 1.80 )2H, m,
2
J ˆ 7 Hz, CH ꢀ, 1.47 )2H, m, J ˆ 7, CH CH ꢀ, 0.98 )3H, t,
2
2
2
2
3
1
3
on a JEOL Lambda 500 instrument )operating at 500 MHz
for H, 125 MHz for 13C, 470 MHz for 19F, and 202 MHz for
J ˆ 7:2, CH ꢀ. C NMR d ˆ 72:1 )OCH ꢀ, 31.5 )CH ꢀ,
31
2 3 3
3
2
2
1
18.5 )CH CH ꢀ, 13.4 )CH ꢀ. P NMR d ˆ 6:0. IR )®lmꢀ
3
1
P spectraꢀ or a JEOL Lambda 300 instrument )operating at
1
n ˆ 1466, 1431, 1387, 1300 )P=Oꢀ, 1147, 1120, 1055, 1032,
À1
3
1
00 MHz for H, 75 MHz for 13C, 282 MHz for 19F, and
21.5 MHz for 31P spectraꢀ as solutions in CDCl , with
1016, 897, 833, 789, 727, 579, 528, 496, 405 cm . HRMS
calculated C H Cl O P 189.972. Found 134.918 [M-C H
3
4
9
2
2
4
9
1
13
35
)2 Â Clꢀ] )error À7.9ꢀ, 136.915 [M-C H )1 Â 35Cl;
internal reference SiMe for H and C, external CFCl for
4
9
3
4 9
1
F and external )MeOꢀ P )d ˆ 140 ppmꢀ for 31P spectra.
37
37
1 Â Clꢀ] )error À4.7ꢀ and 138.912 [M-C H )2 Â Clꢀ]
4 9
3
Data are recorded as follows: chemical shifts in ppm from
reference on the d scale, integration, multiplicity )s: singlet,
d: doublet, t: triplet, q: quartet, m: multiplet and sep: septet;
br: broadꢀ, coupling constant )J, Hzꢀ 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±
MSꢀ using a Finnigan MAT GCQ instrument with chemical
ionisation )CIꢀ 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
spectrometry )HRMSꢀ on a Micromass Autospec SQ Double
Focusing Magnetic Sector instrument. Mode: positive ion
electron impact, magnet scan m/z 400±100 )seconds per
decadeꢀ, resolution 2900. Inlet: septum )1608Cꢀ, 0.2 ml
)error À5.4ꢀ.
4.2. General procedure for dialkyl alkyl phosphates
A solution of the appropriate alcohol )0.025 molꢀ and
triethylamine )0.025 molꢀ in ether )15 mlꢀ was added drop-
wise by cannula to a stirred solution of the appropriate alkyl
phosphorodichloridate )0.011 molꢀ in ether )35 mlꢀ cooled
to 0±58C under argon. The mixture was allowed to warm to
room temperature and left for 14 h; GC±MS analysis
showed varying extents of reaction. To ensure full conver-
sion to the phosphate, a catalytic amount of DMAP was
added before re¯uxing the mixtures )5±15 hꢀ. The precipi-
tate was removed and the ®ltrate concentrated to give a
mobile liquid that was distilled under reduced pressure
)vacuum between 0.02±0.03 mmHgꢀ.

110
C.M. Timperley, M.J. Waters / Journal of Fluorine Chemistry 109 ꢀ2001) 103±111
4
.2.1. Dimethyl isopropyl phosphate ꢀ10h)
Synthesised by methanolysis of isopropyl phosphorodi-
)40 mlꢀ cooled to 0±58C. The mixture was allowed to warm
to room temperature and left for 14 h; analysis by GC±MS
showed incomplete conversion to the phosphate. To drive the
reaction to completion, a catalytic amount of DMAP was
added and the mixture re¯uxed for 5 h. The precipitate was
removed by ®ltration and the ®ltrate concentrated. Fractio-
nation of the residue under reduced pressure gave the title
compound as a colourless liquid )bp 468C/0.03 mmHgꢀ.
Yield 21% and purity >90% by phosphorus NMR analysis.
chloridate; 15 h of re¯ux were required to drive the reaction
to completion. The crude product was distilled using a
Kugelrohr apparatus to give the title compound as a colour-
less liquid )bp 618C/0.03 mmHgꢀ. Yield 52% and purity
>
1
97% by phosphorus NMR analysis. H NMR d ˆ 4:66
)
1H, dsep, J ˆ 6:1 Hz, OCHꢀ, 3.75 )6H, d, J ˆ 10:4 Hz,
13
3 3
OCH ꢀ, 1.35 )6H, d, J ˆ 6:4 Hz, CH ꢀ. C NMR d ˆ 72:6
31
1
)
)
8
1
OCHꢀ, 53.9 )OCH ꢀ, 23.4 )CH ꢀ. P NMR d ˆ À0:6. IR
H NMR d ˆ 4:65 )1H, dsep, J ˆ 7 and 7 Hz, OCHꢀ, 4.1
3
3
®lmꢀ n ˆ 1466, 1389, 1269 )P=Oꢀ, 1182, 1144, 1009, 899,
)4H, dq, J ˆ 7 and 7 Hz, OCH ꢀ, 1.3 )6H, dt, J ˆ 1:2 and
2
À1
13
47, 802, 746, 513 cm . HRMS calculated C H O P
5
7 Hz, ethyl CH ꢀ, 1.3 )6H, d, J ˆ 6 Hz, isopropyl CH ꢀ.
C
13
4
3
3
‡
68.055 )‰M-CH3Š ˆ 153:020ꢀ. Found 153.032 [M-CH ]
NMR d ˆ 72:4 )OCHꢀ, 63.4 )OCH ꢀ, 23.6 )isopropyl CH ꢀ,
31
3
3
2
3
)
error 0ꢀ.
16.1 )ethyl CH ꢀ. P NMR d ˆ À2:8. IR )®lmꢀ n ˆ 1466,
1389, 1377, 1263 )P=Oꢀ, 1167, 1144, 1101, 1034, 1009, 895,
800, 746, 552, 492, 434 cm . HRMS calculated C H O P
À1
4
.2.2. Dimethyl butyl phosphate ꢀ11h)
Synthesised by methanolysis of butyl phosphorodichlor-
7
17 4
‡
196.086 )‰M-C H Š ˆ 157:029ꢀ. Found 155.047 [M-C H ]
3
3
3 3
idate; 5 h of re¯ux were required to drive the reaction to
completion. The crude product was distilled using a Kugel-
rohr apparatus to give the title compound as a colourless
liquid )bp 708C/0.02 mmHgꢀ. Yield 49% and purity >95%
)error À15.3ꢀ.
4.4. Synthesis of triꢀs-butyl) phosphate ꢀ26h)
1
by phosphorus NMR analysis. H NMR d ˆ 4:06 )2H, dt,
A solution of s-butanol )0.115 molꢀ in THF )40 mlꢀ was
added dropwise to a stirred suspension of sodium hydride
)0.115 molꢀ in THF )40 mlꢀ cooled to 0±58C. The mixture
was warmed to room temperature and left for 2 h. A solution
of phosphorus oxychloride )0.033 molꢀ in THF )50 mlꢀ was
added dropwise to the mixture at 0±58C. After addition, the
reaction mixture was allowed to warm to room temperature
and left for 14 h; analysis by GC±MS revealed >95%
product. The very ®ne precipitate was removed using special
J ˆ 6:7 and 6.7 Hz, OCH ꢀ, 3.77 )6H, d, J ˆ 9 Hz, OCH ꢀ,
2
3
1
.67 )2H, m, J ˆ 7 Hz, CH ꢀ, 1.43 )2H, m, J ˆ 7 Hz,
13
2 3 3
2
CH CH ꢀ, 0.95 )3H, t, J ˆ 7 Hz, CH ꢀ.
C NMR
d ˆ 67:6 )OCH ꢀ, 54.1 )OCH ꢀ, 32.1 )CH2ꢀ, 18.5
2
3
31
)
CH CH ꢀ, 13.4 )CH ꢀ. P NMR d ˆ À0:5. IR )®lmꢀ
2
3
3
n ˆ 1646, 1466, 1398, 1282 )P=Oꢀ, 1188, 1036, 906, 850,
À1
7
60, 511 cm . HRMS calculated C H O P 182.071
6
15 4
‡
)
1
‰M-C2H5Š ˆ 153:009ꢀ. Found 153.031 [M-C H ] )error
2
5
1
.2ꢀ.
®lter paper )Whatman silicone-treated phase-separatorꢀ
and the ®ltrate concentrated to give a liquid. Distillation
under reduced pressure gave the title compound as a colour-
less liquid )bp 808C/0.015 mmHg, lit. 119±1298C/8±12mm
Hg [24] ꢀ. Yield 10% and purity >95% by phosphorus NMR
4
.2.3. Dipropyl butyl phosphate ꢀ33h)
Synthesised by propanolysis of butyl phosphorodichlor-
idate; 5 h of re¯ux were required to drive the reaction to
completion. The crude product was distilled using a Kugel-
rohr apparatus to give the title compound as a colourless
liquid )bp 608C/0.02 mmHgꢀ. Yield 73% and purity >99%
1
analysis. H NMR d ˆ 4:42 )3H, m, OCHꢀ, 1.67 )3H, m,
J ˆ 14, 7 and 7 Hz, proton of CH groupꢀ, 1.59 )3H, m,
2
J ˆ 14, 6 and 6 Hz, proton of CH groupꢀ, 1.31 )9H, d,
2
1
13
by phosphorus NMR analysis. H NMR d ˆ 4:05 )2H, dt,
J ˆ 6:4 Hz, OCHCH ꢀ, 0.95 )9H, t, J ˆ 7:3 Hz, CH ꢀ.
C
3
3
J ˆ 6:7 and 6.7 Hz, butyl OCH ꢀ, 3.99 )4H, dt, J ˆ 6:7 and
NMR d ˆ 76:5 )OCHꢀ, 30.2 )CH ꢀ, 20.8 )OCHCH ꢀ, 9.3
2
2
3
3
1
6
.7 Hz, propyl OCH ꢀ, 1.71 )6H, complex m, J ˆ 7 Hz,
)CH ꢀ. P NMR d ˆ À3:44 and À3.48. IR )®lmꢀ n ˆ 1464,
2
3
butyl and propyl CH ꢀ, 1.42 )2H, m, J ˆ 7 Hz, butyl
1383, 1259 )P=Oꢀ, 1174, 1149, 1126, 1097, 1028, 997, 866,
818, 746, 592, 550 cm . HRMS calculated C H O P
2
À1
CH CH ꢀ, 0.97 )6H, t, J ˆ 7 Hz, propyl CH ꢀ, 0.94 )3H,
2
3
3
12 27 4
1
3
t, J ˆ 7 Hz, CH ꢀ. C NMR d ˆ 69 )propyl OCH ꢀ, 67.3
266.165. The compound did not give a useful mass spec-
trum.
3
2
)butyl OCH ꢀ, 32.2 )butyl CH ꢀ, 23.6 )propyl CH ꢀ, 18.6
2 2 2
)
butyl CH CH ꢀ, 13.5 )butyl CH ꢀ, 10 )propyl CH ꢀ. 31P
2
3
3
3
NMR d ˆ À1:6. IR )®lmꢀ n ˆ 1599, 1466, 1379, 1279
À1
)
P=Oꢀ, 1151, 1007, 864, 750, 546, 403 cm . HRMS cal-
5. Conclusion
‡
culated C H O P 238.133 )‰M-C H Š ˆ 197:060ꢀ.
1
0
23
4
3
5
Found 197.097 [M-C H ] )error À14.1ꢀ.
Fluorination of phosphoryl compounds generally pro-
duces compounds of similar or lower boiling point than
the un¯uorinated parent compounds. Those with terminal ±
3
5
4
.3. Synthesis of diethyl isopropyl phosphate ꢀ14h)
CF in the ester groups have the lowest boiling points due to
3
A solution of isopropanol )0.03 molꢀ and triethylamine
0.03 molꢀ in ether )20 mlꢀ was added dropwise to a stirred
low forces of attraction in the liquid state. Those with
terminal ±CF H in the ester groups are an exception Ð
they have high boiling points due presumably to strong
)
solution of diethyl phosphorochloridate )0.03 molꢀ in ether
2

C.M. Timperley, M.J. Waters / Journal of Fluorine Chemistry 109 ꢀ2001) 103±111
111
[
[
[
4] C.M. Timperley, M. Bird, J.F. Broderick, I. Holden, I.J. Morton, M.J.
Waters, J. Fluorine Chem. 104 )2000ꢀ 215.
intermolecular hydrogen±¯uorine bonds. Compounds
shielded by an umbrella of ¯uorine atoms boil at the lowest
temperatures. The boiling points )at atmospheric pressureꢀ
quoted in the tables were derived from extrapolation using a
pressure±temperature nomograph. Any error in the extra-
polation will be the same for all compounds. This has
allowed comparative trends to be seen. However, accurate
measurement of boiling point for a range of ¯uorinated and
un¯uorinated phosphoryl compounds at 760 mmHg are
required before a detailed analysis of the physical effects
of ¯uorination can be undertaken.
5] C.M. Timperley, J.F. Broderick, I. Holden, I.J. Morton, M.J. Waters,
J. Fluorine Chem. 106 )2000ꢀ 43.
6] C.M. Timperley, I. Holden, I.J. Morton, M.J. Waters, J. Fluorine
Chem. 106 )2000ꢀ 153.
7] K.L. Godfrey, US Patent 2 852 550 )1958ꢀ.
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[
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Many thanks to Alison Bussey and Steve Marriott for
providing the infrared data, to Ian Holden for providing the
NMR data, and to Ian Morton for providing the HRMS data
for the compounds synthesised in this study. We also wish to
thank the Ministry of Defence, UK for funding the work.
16] C.M. Timperley, M.J. Waters, 2000, unpublished data.
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