Fluorinated phosphorus compounds - Part 7. The reactions of bis(fluoroalkyl) phosphorochloridates with nitrogen nucleophiles

Article abstract of DOI:10.1016/S0022-1139(01)00493-6

Forty bis(fluoroalkyl) phosphoramidates (R_FO)₂P(O)R were prepared in 10-91% yield by treating phosphorochloridates (R_FO)₂P(O)Cl where R_F was HCF₂CH₂, HCF₂CF₂

Full text of DOI:10.1016/S0022-1139(01)00493-6

Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
Fluorinated phosphorus compounds
Part 7. The reactions of bisꢀ¯uoroalkyl) phosphorochloridates
with nitrogen nucleophiles
*
Christopher M. Timperley , Stephen N. Marriott, Matthew J. Waters
Defence Science and Technology Laboratory, Chemical and Biological Sciences, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK
Received 12 June 2001; received in revised form 17 August 2001
Abstract
Forty bisꢀ¯uoroalkyl) phosphoramidates ꢀR
where R was HCF CH , HCF CF CH , HCF CF CF CF CH , CF CH , C F CH , C F CH , ꢀCF ) CH, ꢀFCH ) CH and ꢀCH ) CF C
F 2 F 2
O) PꢀO)R were prepared in 10±91% yield by treating phosphorochloridates ꢀR O) PꢀO)Cl
F
2
2
2
2
2
2
2
2
2
2
3
2
2
5
2
3
7
2
3 2
2 2
3 2
3
with nucleophiles HR, where R was NH
[
2
, NHMe, NMe
2
, NHEt and NEt
2
in diethyl ether at 0±5 8C. The bulky chloridate
ꢀCH CF CO] PꢀO)Cl reacted with ammonia, methylamine, dimethylamine and ethylamine, but not with diethylamineÐeven on heating
3
)
2
3
2
in the presence of 4-dimethylaminopyridineÐdue to steric hindrance at phosphorus. Fluorinated phosphoramidates have lower basicity and
nucleophilicity than their un¯uorinated counterparts: ꢀEtO) PꢀO)NH is more easily hydrolysed by HCl than ꢀCF CH O) PꢀO)NH and
2
2
3
2
2
2
whereas, ꢀEtO)
respectively, ꢀCF
uorinated species, ꢀCF CH O) PꢀO)NHOMe and ꢀCF CH O) PꢀO)N , were prepared by nucleophilic substitution of bisꢀtri¯uoroethyl)
2
PꢀO)NH
2
is known to react with oxalyl chloride and thionyl chloride to give ꢀEtO)
2
PꢀO)NCO and ꢀEtO)
2
PꢀO)NSO
3
CH O)
2
2
PꢀO)NH reacted only with oxalyl chloride to give ꢀCF CH O) PꢀO)NCO in 10% yield. Two other new
2
3
2
2
¯
3
2
2
3
2
2
3
phosphorochloridate with methoxyamine and azide ion. Published by Elsevier Science B.V.
Keywords: Bisꢀ¯uoroalkyl) phosphoramidate; Bisꢀ¯uoroalkyl) phosphorochloridate; Bisꢀtri¯uoroethyl) N-alkoxyphosphoramidate; Bisꢀtri¯uoroethyl)
phosphorazidate; Bisꢀtri¯uoroethyl) phosphoroisocyanidate
1
. Introduction
The previous paper in this series described the synthesis of
some bisꢀ¯uoroalkyl) phosphites A that were converted into
the corresponding chloridates B [1]. The discovery of this
route opens up a new ®eld of research as many of the
reactions of dialkyl phosphorochloridates might be realised
1
with bisꢀ¯uoroalkyl) phosphorochloridates.
To understand the differences between un¯uorinated and
uorinated systems, two main factors must be understood:
the steric and electronic effects of replacing a proton with a
¯
¯
uorine atom. A ¯uorine atom is larger ꢀatomic van der
Ê
Waals' radii, F ˆ 1:35 and H ˆ 1:2 A) and much more
*
Corresponding author. Tel.: ‡44-1980-613566;
electronegative ꢀon Pauling's scale, F ˆ 4:0 and H ˆ 2:1)
fax: ‡44-1980-613371.
[
2±5]. Replacement of protons with ¯uorine atoms alters
E-mail address: cmtimperley@dstl.gov.uk ꢀC.M. Timperley).
1
steric and electronic parameters, and this is well illustrated
in the case of ¯uoroalkyl phosphorus compounds. For
example, although it is useful to compare ꢀCH CH O)
Organic phosphorus compounds are named after the corresponding
parent acids. The substances described in this paper are derivatives of
phosphoric acid ꢀHO)
bisꢀfluoroalkyl) phosphorochloridates. Their amino derivatives are phos-
phoramidates ꢀR O) PꢀO)NH N-alkylphosphoramidates ꢀR O)2-
PꢀO)NHR and N,N-dialkylphosphoramidates ꢀR O) PꢀO)NR
Compounds of structure ꢀR O) PꢀO)NCO are phosphoroisocyanidates,
those of structure ꢀR O) PꢀO)NHOR are N-alkoxyphosphoramidates,
while those of structure ꢀR O) PꢀO)N are phosphorazidates.
3 F 2
P=O. Compounds of structure ꢀR O) PꢀO)Cl are
3
2
2-
PꢀO)Cl with ꢀCF CH O) PꢀO)Cl, they have very different
3
2
2
F
2
2
,
F
characters; the latter has a more electrophilic and hindered
phosphorus atom ꢀwhat extent these opposing effects
in¯uence the reactivities of the ¯uorinated phosphoroha-
lidates to nucleophiles is unknown). Comparison of the van
F
2
2
.
F
2
F
2
F
2
3
0022-1139/02/$ ± see front matter. Published by Elsevier Science B.V.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 4 9 3 - 6

1
12
C.M. Timperley et al. / Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
À1
3
der Waals volumes of CH ꢀ13.7 cm mol ) and CF3
3
3
À1
21.3 cm mol ) suggests the CF group approximates
3
ꢀ
to an isopropyl group in size [2±5]. When comparing
CH CH O) PꢀO)Cl with ꢀCF CH O) PꢀO)Cl, it is helpful
to picture the latter as having the dimensions of [i-
ꢀ
3
2
2
3
2
2
PrCH O] PꢀO)Cl, but with a phosphorus atom of reversed
2
2
2
polarity. Such analogy cannot be extended to many other
per¯uoroalkyl groups as steric parameters have not yet
been reported. A simple way to probe such effects is to
examine reactions between a range of homologous elec-
trophiles and nucleophiles.
Here, we describe the interactions of bisꢀ¯uoroalkyl)
phosphorochloridates B with ammonia, and primary and
secondary amines with one to four carbon atoms, and some
properties of the products C. This work extends our earlier
studies on the synthesis of ¯uoroalkyl-substituted phosphor-
amidates [7].
Other approaches have been studied less. The reverse
0
0
reaction of N,N,N ,N -tetra-alkylphosphoramidic chlorides
ꢀR N) PꢀO)Cl with ¯uoroalcohols, is much slower because
2
2
of the poorly electrophilic and hindered phosphorus atom
of the amidic chloride and the low nucleophilicity of the
¯
uoroalcohol. Even with 4-dimethylaminopyridine cata-
lyst, phosphorylation is slow [7]. The Arbusov reaction
of trisꢀ¯uoroalkyl) phosphites with N-chloramines, illu-
strated below [11], is of low utility due to the poor avail-
ability of both reagents.
One of the aims was to ®nd the point at which steric
hindrance prevented product formation. Another was to
demonstrate the powerful phosphorylation action of bisꢀ¯uor-
oalkyl) phosphorochloridates; subsequent papers will des-
cribe the phosphorylation of other nucleophiles such as thiols
and alcohols.
Nothing is known about the chemistry of bisꢀ¯uoroalkyl)
phosphoramidates, besides the inertness of ꢀCF CH O)
2-
3
2
The synthesis of ¯uoroalkyl phosphoramidates has
advanced little since Lenton and Lewis prepared HCF2-
CF CH OPꢀO)ꢀNH ) in 1965 [8]. Like the analogues
PꢀO)NMe to acid hydrolysis [7]. We now describe the
2
preparation of a homologous series of such molecules,
and examine the behaviour of ꢀCF CH O) PꢀO)NH to
2
2
2 2
3
2
2
2
CF CH OPꢀO)R where R is NMe , NMeEt or NEt
2
certain electrophiles ꢀHCl, oxalyl chloride and thionyl chlor-
ide). The chemical and physical properties of the new
phosphoramidates are compared with conventional analo-
gues that do not contain ¯uorine. Also described are the ®rst
examples of two new classes of bisꢀ¯uoroalkyl) phosphoryl
species, the N-alkoxyphosphoramidate ꢀCF CH O) PꢀO)N-
3
2
2
2
[
7], it was made by treating tri¯uoroethyl phosphorodi-
chloridate with four molar equivalents of nitrogen nucleo-
phile. Phosphoramidates containing a 2-¯uoroethyl group,
reported by Kabachnik et al. [9], were made in the same
way:
3
2
2
HOMe and the phosphorazidate ꢀCF CH O) PꢀO)N .
3
2
2
3
2. Results and discussion
2.1. Phosphoramidates of structure
Phosphoramidates containing two ¯uoroalkyl groups
were derived from the bisꢀ¯uoroalkyl) phosphorochloridate
[HꢀCF ) CH O] PꢀO)NR
2 n 2 2 2
[
7,10,11]:
Only three compounds obeying this formula appear in
the literature: [HꢀCF ) CH O] PꢀO)NHPh and [HꢀCF ) -
CH O] PꢀO)NꢀCH ) O where n is 2 or 4 [11]. We found
that treatment of bisꢀa,a,o-trihydroper¯uoroalkyl) phos-
phorochloridates with ammonia and amines gave phosphor-
amidates 1a±e, 2a±e and 3a±e. Reaction was instantaneous.
2
2
2
2
2 n
2
2
2
2 2
3 2
Acid dissociation constants measured in ethanol for ꢀCH CH O)2-
3 2 2
PꢀO)OH and ꢀCF CH O) PꢀO)OH are 6.8 and 4.1 respectively [6]. These
data show the increase in acidity caused by replacement of the electron-
donating ethyl group with the electron-withdrawing trifluoroethyl group.

C.M. Timperley et al. / Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
113
vibrations in the infrared spectra for the phosphoryl group
ꢀP=O) and the phosphoramido group ꢀP±N) appear at 1236±
À1
1
265 and 945±976 cm respectively.
2
.2. Phosphoramidates of structure ꢀR CH O) PꢀO)NR
2
F
2
2
Replacing the o-proton of ¯uoroalcohols of structure
HꢀCF ) CH OH with a o-¯uorine atom produces ¯uoroal-
2
n
2
cohols of structure FꢀCF ) CH OH. Both classes of ¯uor-
2
n
2
oalcohols have similar acidities. The acid dissociation
constant, for example, of di¯uoroethanol is 12 while that
of tri¯uoroethanol is 12.4 [13]. In phosphoryl compounds,
the introduction of ¯uoro-ester groups increases the acid
strength without changing the general rules known for
¯
uoroalcohols or ¯uorocarboxylic acids [6]. The dissocia-
tion constants measured in absolute ethanol for the two
phosphoric acids [HꢀCF ) CH O] PꢀO)OH and [FꢀCF ) -
CH O] PꢀO)OH are 4.15 and 4.18, respectively [6]. The pair
2
2
2
2
2 3
2
2
of chloridates, [HꢀCF ) CH O] PꢀO)Cl and [C F CH O]
2-
2
2
2
2
2
5
2
PꢀO)Cl will contain phosphorus atoms of comparable elec-
trophilicity ꢀdue to similar inductive effects) and steric
accessibility ꢀas the ends of the ¯uoro-ester groups are
suf®ciently distant from phosphorus). They should therefore
react with nucleophiles in the same way.
Phosphoryl compounds containing the di¯uoroethyl
group are rare. The ®rst, trisꢀdi¯uoroethyl) phosphate
ꢀ
HCF CH O) P=O, was made in 1909 by Swarts from
2
Bisꢀtri¯uoroethyl) phosphorochloridate underwent facile
ammonolysis and gave the phosphoramidate 4 in excellent
yield. Derivatives containing the methylamino, dimethyla-
mino, ethylamino and diethylamino groups are described in
Part 1 [7]. Bisꢀpenta¯uoropropyl) and bisꢀhepta¯uorobutyl)
phosphorochloridates gave compounds 5a±e and 6a±e
respectively.
2
3
di¯uoroethanol, bromine and red phosphorus [12]. To the
best of our knowledge, over 90 years elapsed before the next
species were isolated: ꢀHCF CH O) PꢀO)H and ꢀHCF -
2
2
2
2
CH O) PꢀO)Cl [1]. Phosphoramidates 1a±e extend this
2
small family.
2
Physical data for the phosphoramidates appear in Tables 1
and 2. Their phosphorus chemical shifts in deuterated
chloroform are between 7.9 and 10.4 ppm. Characteristic
Table 1
Experimental data for phosphoramidates [HꢀCF
2
)
n
2 2
CH O] PꢀO)R
a
Compound
R
Bp ꢀ8C/mmHg)
Mp ꢀ8C)
n ˆ 1
Bisꢀdifluoroethyl) phosphoramidates
1
1
1
1
1
a
b
c
NH
NHMe
NMe
NHEt
NEt
2
80/0.015
71/0.015
58/0.02
65/0.015
62/0.02
±
±
±
±
±
2
d
e
2
n ˆ 2
Bisꢀtetrafluoropropyl) phosphoramidates
2
2
2
2
2
a
b
c
NH
NHMe
NMe
NHEt
NEt
2
88/0.015
83/0.01
62/0.015
75/0.01
69/0.015
36
40
±
2
d
e
±
2
±
n ˆ 4
Bisꢀoctafluoropentyl) phosphoramidates
3
3
3
3
3
a
b
c
NH
NHMe
NMe
NHEt
NEt
2
83/0.015
75/0.015
65/0.01
84/0.02
68/0.01
±
±
±
±
±
Physical data for the phosphoramidates appear in Tables 3
and 4. Their phosphorus chemical shifts in deuterated
chloroform are between 7.7 and 9.5 ppm. The infrared
spectra are complex due to many overlapping bands from
the P±N bond. It was not possible to assign the peaks
unambiguously.
2
d
e
2
a
Approximate oven temperatures for bulb-to-bulb distillations are
quoted.

Table 2
2 n 2 2 3
Spectroscopic data for bisꢀfluoroalkyl) phosphoramidates [HꢀCF ) CH O] PꢀO)R 1a±e, 2a±e and 3a±e ꢀNMR data measured in CDCl )
a
1
13
19
31
À1
P NMR d IR n ꢀcm )
Compound
H NMR d, J ꢀHz)
C NMR d, J ꢀHz)
F NMR d
Elemental analysis ꢀ%)
1
1
a ꢀM
w
225)
239)
6.0 ꢀ2H, tt, J ˆ 4, 55, CF
2
H), 4.2 ꢀ4H, ddt,
112.8 ꢀdt, J ˆ 9, 242, CF
2
H),
À126.4 ꢀ4F, dt, J ˆ 14, 14, CF
2
H)
H)
9.9
1568, 1456, 1429, 1373, 1329, 1248 ꢀP=O),
1146, 1086, 945 ꢀP±N), 903, 856
Calcd. for C
4 8 4 3
H F NO P: C, 21.3; H, 3.6; F, 33.8;
J ˆ 4, 8, 14, OCH ), 3.7 ꢀ2H, d, J ˆ 6, NH
2
2
)
64.2 ꢀdt, J ˆ 4, 29, OCH
113.6 ꢀdt, J ˆ 8, 242, CF
2
)
N, 6.2. Found: C, 21.1; H, 3.7; F, 33.7; N, 6.1.
b ꢀM
w
5.94 ꢀ2H, tt, J ˆ 4, 55, CF
2
H), 4.16 ꢀ4H, ddt,
2
H), 64.4
À125.7 ꢀ4F, dt, J ˆ 14, 14, CF
2
10.0
1641, 1456, 1429, 1375, 1327, 1244 ꢀP=O),
1146, 1082, 953 ꢀP±N), 906
5 10 4 3
Calcd. for C H F NO P: C, 25.1; H, 4.2; F, 31.8;
J ˆ 4, 9, 15, OCH ), 3.32 ꢀ1H, m, NH), 2.62
2
ꢀdt, J ˆ 5, 31, OCH
2 3
), 25.9 ꢀs, NHCH )
N, 5.9. Found: C, 25; H, 4.1; F, 31.7; N, 5.9.
ꢀ
3H, dd, J ˆ 6, 13, NCH
3
)
1
1
c ꢀM
w
253)
253)
5.94 ꢀ2H, tt, J ˆ 4, 55, CF
2
H), 4.14 ꢀ4H, m,
111.9 ꢀdt, J ˆ 8, 241, CF
2
H), 64.0
À125.7 ꢀ4F, dt, J ˆ 13, 25, CF
2
H)
H)
10.4
8.9
1458, 1427, 1317, 1250 ꢀP=O), 1144, 1078,
1047, 1005, 949 ꢀP±N), 903, 839
Calcd. for C
6 12 4 3
H F NO P: C, 28.5; H, 4.7; F, 30;
OCH
2
), 2.74 ꢀ6H, d, J ˆ 10, NCH
3
)
ꢀdt, J ˆ 5, 30, OCH ), 35.5 ꢀd, J ˆ 3, NCH
2
3
)
N, 5.5. Found: C, 28.4; H, 4.6; F, 29.9; N, 5.4.
d ꢀM
w
5.95 ꢀ2H, tt, J ˆ 4, 55, CF
2
H), 4.23 ꢀ4H, m,
), 3.25 ꢀ1H, m, NH) 2.99 ꢀ2H, m,
), 1.17 ꢀ3H, dt, J ˆ 1, 7, CH
111.2 ꢀdt, J ˆ 8, 241, CF
2
H), 63.4
À125.9 ꢀ4F, dt, J ˆ 13, 26, CF
2
1456, 1429, 1373, 1327, 1244 ꢀP=O), 1144,
1078, 976 ꢀP±N), 947, 904, 872
6 12 4 3
Calcd. for C H F NO P: C, 28.5; H, 4.7; F, 30;
OCH
NCH
2
ꢀdt, J ˆ 4, 30, OCH ), 36.9 ꢀs, NCH
2
2
),
N, 5.5. Found: C, 28.5; H, 4.6; F, 30.1; N, 5.4.
2
3
)
17.3 ꢀd, J ˆ 6, CH
3
)
1
2
2
2
2
e ꢀM
w
281)
325)
339)
353)
353)
5.96 ꢀ2H, tt, J ˆ 4, 55, CF
OCH
6H, t, J ˆ 7, CH
2
H), 4.14 ꢀ4H, m,
), 1.11
112.6 ꢀdt, J ˆ 9, 242, CF
ꢀdt, J ˆ 4, 30, OCH ), 39.3
ꢀd, J ˆ 4, NCH ), 13.2 ꢀs, CH
2
H), 63.8
À126.8 ꢀ4F, dt, J ˆ 13, 26, CF
2
H)
9.8
8.8
9.0
9.6
8.1
1633, 1456, 1427, 1385, 1327, 1252 ꢀP=O), 1213, Calcd. for C
8
H
16
F
4
NO
3
P: C, 34.2; H, 5.7; F, 27;
2
), 3.13 ꢀ4H, dt, J ˆ 7, 12, NCH
2
2
1144, 1080, 1038, 962 ꢀP±N), 945, 903, 839
N, 5. Found: C, 34.1; H, 5.5; F, 26.8; N, 4.9.
ꢀ
3
)
2
3
)
a ꢀM
w
5.94 ꢀ2H, tt, J ˆ 4, 53, CF
J ˆ 11, 12, OCH
2
H), 4.4 ꢀ4H, dt,
113.8 ꢀdtt, J ˆ 7, 34, 256, CF
H), 62.1
2
), 109.3
À137.5 ꢀ4F, d, J ˆ 53, CF
2
H),
1566, 1460, 1402, 1348, 1238 ꢀP=O),
1213, 1105, 1068, 989, 951 ꢀP±N)
Calcd. for C
6 8 8 3
H F NO P: C, 22.2; H, 2.5; F, 46.8;
2
), 3.48 ꢀ2H, m, NH
2
)
ꢀtt, J ˆ 36, 250, CF
2
À124.6 ꢀ4F, dt, J ˆ 5, 13, CF
2
)
N, 4.3. Found C, 22.2; H, 2.5; F, 46.6; N, 4.1.
ꢀdt, J ˆ 5, 30, OCH
2
)
b ꢀM
w
5.92 ꢀ2H, tt, J ˆ 4, 53, CF
J ˆ 11, 12, OCH ), 3.06 ꢀ1H, m, NH), 2.65
3H, dd, J ˆ 6, 13, CH
2
H), 4.36 ꢀ4H, dt,
114.9 ꢀm, CF
2
), 109 ꢀtt, J ˆ 36, 250,
),
À136.9 ꢀ4F, d, J ˆ 53, CF
2
H),
1460, 1402, 1356, 1257, 1236 ꢀP=O),
7 10 8 3
Calcd. for C H F NO P: C, 24.8; H, 2.9; F, 44.8;
2
CF
2
H), 62.2 ꢀdt, J ˆ 5, 30, OCH
2
À123.9 ꢀ4F, dt, J ˆ 8, 16, CF
2
)
1211, 1109, 1066, 951 ꢀP±N), 937, 874, 833
N, 4.1. Found: C, 24.8; H, 3; F, 43.9; N, 4.1.
ꢀ
3
)
27.5 ꢀNHCH )
3
c ꢀM
w
5.94 ꢀ2H, tt, J ˆ 4, 53, CF
2
H), 4.3 ꢀ4H, dt,
114 ꢀtt, J ˆ 9, 250, CF
ꢀtt, J ˆ 36, 250, CF H), 62.2 ꢀdt, J ˆ 5,
0, OCH
), 36.4 ꢀd, J ˆ 4, NCH
2
), 109.1
À136.9 ꢀ4F, dt, J ˆ 17, 53, CF
2
H),
1489, 1460, 1414, 1319, 1259, 1236 ꢀP=O),
1211, 1190, 1107, 1061, 1007, 951 ꢀP±N), 937
Calcd. for C
8 12 8 3
H F NO P: C, 27.2; H, 3.4; F, 43.1;
J ˆ 11, 12, OCH ), 2.71 ꢀ6H, d, J ˆ 10, NCH
2
3
)
2
À123.9 ꢀ4F, dt, J ˆ 9, 18, CF
2
)
N, 4. Found: C, 27.2; H, 3.3; F, 43.1; N, 3.8.
3
2
3
)
d ꢀM
w
5.91 ꢀ2H, tt, J ˆ 4, 53, CF
J ˆ 11, 13, OCH ), 3.34 ꢀ1H, m, NH), 2.99
2H, m, NCH
), 1.16 ꢀ3H, dt, J ˆ 1, 7, CH
2
H), 4.3 ꢀ4H, dt,
114.1 ꢀtt, J ˆ 10, 250, CF
2
), 108.9
À136.9 ꢀ4F, dt, J ˆ 17, 55, CF
2
H),
1458, 1441, 1356, 1286, 1236 ꢀP=O), 1213,
1109, 1066, 968, 951 ꢀP±N), 937, 877, 835
Calcd. for C
8 12 8 3
H F NO P: C, 27.2; H, 3.4; F, 43.1;
2
ꢀtt, J ˆ 36, 250, CF H), 62.1 ꢀdt,
J ˆ 4, 26, OCH ), 36.4 ꢀm, NCH
6.8 ꢀd, J ˆ 6, CH
2
À124.2 ꢀ4F, dt, J ˆ 9, 18, CF
2
)
N, 4. Found: C, 27; H, 3.3; F, 43.2; N, 3.9.
ꢀ
2
3
)
2
2
),
1
3
)
2
3
3
3
3
e ꢀM
w
381)
525)
539)
553)
553)
5.91 ꢀ2H, tt, J ˆ 4, 53, CF
J ˆ 12, 14, OCH ), 3.11 ꢀ4H, q, J ˆ 7, NCH
.13 ꢀ6H, t, J ˆ 7, CH
2
H), 4.32 ꢀ4H, dt,
114.1 ꢀtt, J ˆ 10, 250, CF
), 250, CF
H), 62.1 ꢀdt, J ˆ 5, 28, OCH
39.8 ꢀm, NCH
), 1.39 ꢀd, J ˆ 7, CH
2
), 109 ꢀtt, J ˆ 36, À137 ꢀ4F, d, J ˆ 53, CF
2
H),
9.1
8.8
9.0
9.5
7.9
1460, 1387, 1267, 1236 ꢀP=O), 1211, 1176,
1107, 1061, 1039, 964 ꢀP±N), 937, 870, 833
Calcd. for C10
16 8 3
H F NO P: C, 31.5; H, 4.2; F, 39.9;
2
2
2
2
),
À124 ꢀ4F, dt, J ˆ 9, 24, CF
2
)
N, 3.7. Found: C, 31.4; H, 4.2; F, 39.8; N, 3.6.
1
3
)
2
3
)
a ꢀM
w
6.06 ꢀ2H, tt, J ˆ 5, 52, CF
2
H), 4.47
108±116 ꢀdtt, J ˆ 5, 29, 248, CF
107.1 ꢀtt, J ˆ 36, 249, CF H),
2.1 ꢀm, OCH
2
2
2
),
),
),
À136.5 ꢀ4F, m, CF
2
H), À129.6,
1564, 1460, 1404, 1261 ꢀP=O), 1173, 1132,
1086, 989, 964 ꢀP±N), 906, 877, 808
8 3
Calcd. for C10H F16NO P: C, 22.9; H, 1.5; F, 57.9;
ꢀ
4H, m, OCH ), 3.48 ꢀ2H, m, NH
2
2
)
2
À124.9 and À120.6 ꢀ12F, m, CF
2
)
N, 2.7. Found: C, 22.8; H, 1.4; F, 57.9; N, 2.8.
6
2
)
b ꢀM
w
6.05 ꢀ2H, tt, J ˆ 5, 52, CF
J ˆ 7, 13, OCH ), 3.29 ꢀ1H, m, NH), 2.65
3H, dd, J ˆ 6, 13, NCH
2
H), 4.44 ꢀ4H, dt,
108±116 ꢀdtt, J ˆ 8, 28, 248, CF
107.4 ꢀtt, J ˆ 36, 249, CF H),
62 ꢀm, OCH ), 26.9 ꢀs, NCH
À136.4 ꢀ4F, m, CF
2
H), À129.1,
1460, 1402, 1362, 1255 ꢀP=O), 1173,
1132, 1012, 991, 960 ꢀP±N), 904, 808
Calcd. for C11
10 3
H F16NO P: C, 24.5; H, 1.9; F,
2
2
À124.4 and À120 ꢀ12F, m, CF
2
)
56.4;
ꢀ
3
)
2
3
)
N, 2.6. Found: C, 24.5; H, 2.1; F, 56.2; N, 2.5.
c ꢀM
w
6.05 ꢀ2H, tt, J ˆ 6, 52, CF
2
H), 4.41
108±116 ꢀdtt, J ˆ 6, 28, 249, CF
107.6 ꢀtt, J ˆ 31, 254, CF
t, J ˆ 28, OCH ), 36.3 ꢀd, J ˆ 4, NCH
À136.6 ꢀ4F, m, CF
2
H), À128.9,
1489, 1460, 1404, 1319, 1265 ꢀP=O), 1174,
1132, 1074, 1009, 960 ꢀP±N), 906, 872, 808
Calcd. for C12
12 3
H F16NO P: C, 26; H, 2.2; F, 55;
ꢀ
4H, m, OCH
2
), 2.73 ꢀ6H, d, J ˆ 11, NCH
3
)
2
H), 62.2
À123.9 and À119.8 ꢀ12F, m, CF
2
2
)
)
N, 2.5. Found: C, 25.8; H, 2.1; F, 54.7; N, 2.4.
ꢀ
2
3
)
d ꢀM
w
6.08 ꢀ2H, tt, J ˆ 5, 52, CF
J ˆ 7, 13, OCH ), 3.21 ꢀ1H, s, NH), 3.0
2H, m, NCH
), 1.16 ꢀ3H, dt, J ˆ 1, 7, CH
2
H), 4.44 ꢀ4H, dt,
108±116 ꢀdtt, J ˆ 6, 29, 245, CF
2
),
À136.9 ꢀ4F, m, CF
2
H), À129.8,
1460, 1441, 1406, 1288, 1252 ꢀP=O), 1174,
1132, 1082, 966 ꢀP±N), 910, 876, 808
Calcd. for C12
12 3
H F16NO P: C, 26; H, 2.2; F, 55;
2
109.6 ꢀtt, J ˆ 30, 246, CF H), 62.2
ꢀt, J ˆ 28, OCH ), 5.7 ꢀs, NCH ),
À13.9 ꢀd, J ˆ 6, CH
2
À124.8 and À120.6 ꢀ12F, m, CF
N, 2.5. Found: C, 25.8; H, 2.2; F, 55.1; N, 2.3.
ꢀ
2
3
)
2
2
3
)
3
e ꢀM
w
581)
6.04 ꢀ2H, tt, J ˆ 5, 52, CF
OCH
), 3.03 ꢀ4H, q, J ˆ 7, NCH
.12 ꢀ6H, t, J ˆ 7, CH
2
H), 4.4 ꢀ4H, m,
113.8 ꢀdtt, J ˆ 7, 32, 248, CF
ꢀtt, J ˆ 32, 254, CF H), 108±110
ꢀm, CF CF ), 61.9 ꢀm, OCH ),
9.6 ꢀd, J ˆ 5, NCH ), 1.32 ꢀm, CH
2
), 107.6
À136.4 ꢀ4F, d, J ˆ 52, CF
2
H), À129.2,
9.0
1460, 1387, 1271 ꢀP=O), 1213, 1174, 1132,
1072, 1041, 991, 964 ꢀP±N), 908, 868, 808
Calcd. for C14
16 3
H F16NO P: 28.9; H, 2.8; F, 52.3;
2
2
),
2
À124.2 and À119.8 ꢀ12F, m, CF
2
)
N, 2.4. Found: C, 28.9; H, 2.8; F, 52.1; N, 2.4.
1
3
)
2
2
2
3
2
3
)
a
All mass spectra ꢀchemical ionisation) displayed a prominent molecular ion M ‡ 1 peak.

C.M. Timperley et al. / Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
115
Table 3
Bis[2-ꢀtri¯uoromethyl)-2-propyl] phosphorochloridate
ꢀCH ) CF CO] PꢀO)Cl, the only chloridate examined with
a tertiary group, combined with ammonia, methylamine,
dimethylamine and ethylamine, giving phosphoramidates
Experimental data for phosphoramidates [R CH
F
2
O]
2
PꢀO)R
[
3
2
3
2
a
Compound
R
Bp ꢀ8C/mmHg)
Mp ꢀ8C)
R
F
ˆ CF
3
Bisꢀtrifluoroethyl) phosphoramidate
9a±d. It did not react with diethylamine even after 14 h of
4
NH
2
±
42±43
heating under re¯ux in the presence of 4-dimethylamino-
pyridine, often a useful phosphorylation catalyst [7]. Its
R
F
ˆ C
2
F
5
Bisꢀpentafluoropropyl) phosphoramidates
5
5
5
5
5
a
b
c
NH
NHMe
NMe
NHEt
NEt
2
76/0.02
56/0.015
36/0.015
58/0.1
35
37
±
inertness cannot be ascribed to electronic effects as ꢀCF3-
2
CH O) PꢀO)Cl reacted readily with diethylamine; the pK of
2
2
a
d
e
30
±
CF CH OH is 12.4 compared to that of ꢀCH ) CF COH
3
2
3 2
3
2
39/0.06
which is 11.6 [14]. It must therefore be a purely steric
phenomenon. Although the hexa¯uoroisopropyl group is
more electronegative than the 2-ꢀtri¯uoromethyl)-2-propyl
group, the latter is probably larger in size.
Bisꢀtri¯uoroethyl) phosphoramidates 7a±e, 8a±e and 9a±
d are the ®rst to have been prepared that contain secondary
and tertiary ¯uoro-ester groups. Physical data appear in
Tables 5 and 6. Their phosphorus chemical shifts in deut-
erated chloroform are between À0.3 and 9.7 ppm.
R
F
ˆ C
3
F
7
Bisꢀheptafluorobutyl) phosphoramidates
6
6
6
6
6
a
b
c
NH
NHMe
NMe
NHEt
NEt
2
±
62
±
66/0.02
46/0.03
63/0.02
50/0.03
2
±
d
e
±
2
±
a
Approximate oven-temperatures for bulb-to-bulb distillations are
quoted.
2
.3. Phosphoramidates of structure ꢀR O) PꢀO)NR
F 2 2
2.4. Some physical properties of bisꢀfluoroalkyl)
phosphoramidates
Pronounced stereoelectronic effects are observed for
bisꢀ¯uoroalkyl) phosphorochloridates containing secondary
and tertiary ¯uoro-ester groups. The electrophilicities of the
three chloridates considered in this section should decrease
in the order [ꢀCF ) CHO] PꢀO)Cl > ‰ꢀCH ) CF CO] PꢀO)
Previously it was shown that the boiling points ꢀbps) of
¯uoroalkyl phosphoryl compounds depend on the location
of the ¯uoroalkyl groups [15]. Fluoroalkyl molecules often
boil at lower temperatures than their un¯uorinated counter-
3
2
2
3 2
3
2
Cl ꢀ ‰ꢀFCH ) CHO] PꢀO)Cl, mirroring pK values for the
2
2
2
a
¯
¯
uoroalcohols: values for hexa¯uoroisopropanol and 2-ꢀtri-
uoromethyl)-2-propyl are 9.3 and 11.6 respectively [14].
parts despite their higher molecular weights ꢀM s), but
w
sometimes boil at higher temperatures due to hydrogen-
¯uorine bonding. This unpredictability is shared by the
bisꢀ¯uoroalkyl) phosphoramidates whose bps and melting
points ꢀmps) follow no simple trend. Whereas, phosphor-
amidates 4, 5a and 7a melt at lower temperatures than their
These chloridates contain a phosphorus atom hindered by
the secondary ¯uoro-ester groups. Although ꢀCF ) CH and
3
2
ꢀ
volumes for CF , FCH and CH are 21.3, 16 and 13.7 cm
CH ) CF C are larger than ꢀFCH ) CHÐvan der Waals
3 2 3 2 2
3
3
2
3
À1
mol [2,3]Ðranking the ®rst two groups in size is dif®cult.
Theaccessibilityofthephosphorusatomsofthetwoisopropyl
chloridates will be [ꢀFCH ) CHO] PꢀO)Cl > ‰ꢀCF ) CHO] -
2
2
2
3 2
2
Table 5
PꢀO)Cl,thereverseoftheirelectrophilicityorder.Despitesuch
antagonistic effects, both chloridates combined with nitrogen
nucleophiles to give phosphoramidates 7a±e and 8a±e.
F 2
Experimental data for phosphoramidates ꢀR O) PꢀO)R
a
Compound
R
Bp ꢀ8C/mmHg)
Mp ꢀ8C)
R
F
3 2
ˆ ꢀCF ) CH
Bisꢀhexafluoroisopropyl) phosphoramidates
7
7
7
7
7
a
b
c
NH
NHMe
NMe
NHEt
NEt
2
85/1
±
32±33
84
±
2
30/0.02
66/0.015
45/0.015
d
e
50
±
2
R
F
ˆ ꢀFCH
2
)
2
CH
Bisꢀdifluoroisopropyl) phosphoramidates
8
8
8
8
8
a
b
c
NH
NHMe
NMe
NHEt
NEt
2
90/0.015
92/0.03
69/0.02
85/0.015
72/0.015
±
34
±
2
d
e
±
2
±
R
F
ˆ ꢀCH
3
)
2
3
CF C
Bisꢀtrifluoro-t-butyl) phosphoramidates
9
9
9
9
a
b
c
NH
NHMe
NMe
NHEt
2
±
148
79
±
±
2
38/0.015
±
d
58
a
Approximate oven temperatures for bulb-to-bulb distillations are
quoted.

Table 4
Spectroscopic data for bisꢀfluoroalkyl) phosphoramidates ꢀR CH
F
2
O)
2 3
PꢀO)R 4, 5a±e and 6a±e ꢀNMR data measured in CDCl )
a
1
13
19
31
À1
IR n ꢀcm )
Compound
H NMR d, J ꢀHz)
C NMR d, J ꢀHz)
F NMR d
P NMR d
Elemental analysis ꢀ%)
4
5
5
5
ꢀM
w
261)
4.34 ꢀ4H, qdd, J ˆ 3, 8, 15, OCH
.65 ꢀ2H, d, J ˆ 5, NH
2
),
122.4 ꢀdq, J ˆ 10, 277, CF
3
),
À84.6 ꢀ6F, m, CF
3
)
9.2
8.7
8.7
9.4
1568, 1458, 1423, 1290, 1254,
1174, 1113, 1078, 964, 879
Calcd. for C
4 6 6 3
H F NO P: C, 18.4; H, 2.3; F, 43.7;
3
2
)
62.4 ꢀdq, J ˆ 4, 38, OCH
2
)
N, 5.4. Found: C, 18.4; H, 2.1; F, 43.5; N, 5.2.
a ꢀM
w
361) 4.38 ꢀ4H, m, OCH ), 3.52 ꢀ2H, m, NH
2
2
)
116.4 ꢀtq, J ˆ 36, 289, CF
3
), 113 ꢀdq, J ˆ 8,
À124.3 ꢀ4F, m, CF
2
),
),
),
1564, 1460, 1377, 1356, 1201, 1165, Calcd. for C
6 6 3
H F10NO P: C, 19.9; H, 1.7; F, 52.6;
2
56, CF
2
), 62.4 ꢀdt, J ˆ 4, 29, OCH
2
)
À83.2 ꢀ6F, m, CF
3
)
1111, 1072, 1030, 956, 935, 877 N, 3.9. Found: C, 20; H, 1.5; F, 52.7; N, 3.8.
b ꢀM
w
375) 4.42 ꢀ4H, dt, J ˆ 7, 12, OCH
2
), 3.01
117.2 ꢀtq, J ˆ 35, 288, CF
3
), 112.4 ꢀdq, J ˆ 8,
À123.6 ꢀ4F, m, CF
2
1377, 1356, 1263, 1203, 1157, 1111, Calcd. for C
7
H
8
3
F10NO P: C, 22.4; H, 2.1; F, 50.7;
ꢀ
1H, m, NH), 2.65 ꢀ3H, dd, J ˆ 6, 12, NCH
3
)
259, CF ), 61.8ꢀdt, J ˆ 4, 29, OCH ), 27.4 ꢀs, CH
2
2
3
)
À82.5 ꢀ6F, m, CF
3
)
1070, 1028, 958, 903, 872, 808
N, 3.7. Found: C, 22.2; H, 2.1; F, 50.7; N, 3.5.
c ꢀM
w
389) 4.42 ꢀ4H, dt, J ˆ 7, 13, OCH
6H, d, J ˆ 11, NCH
2
), 2.81
118.6 ꢀtq, J ˆ 34, 287, CF
3
), 112 ꢀdq, J ˆ 9,
À123.7 ꢀ4F, m, CF
2
1489, 1460, 1408, 1375, 1356,
1321, 1273, 1205, 1155, 1111,
1066, 1028, 1009, 937, 874
Calcd. For C
8 10 3
H F10NO P: C, 24.7; H, 2.6; F, 48.8;
ꢀ
3
)
256, CF ), 62 ꢀdt, J ˆ 5, 29, OCH ),
2
2
À82.6 ꢀ6F, m, CF
3
)
N, 3.6. Found: C, 24.6; H, 2.6; F, 48.6; N, 3.4.
3
6.3 ꢀd, J ˆ 3, NCH
3
)
5
5
d ꢀM
w
389) 4.42 ꢀ4H, dt, J ˆ 7, 13, OCH
.0 ꢀ2H, dd, J ˆ 7, 11, NCH
3H, dd, J ˆ 1, 7, CH
2
), 3.2 ꢀ1H, m, NH),
116.9 ꢀm, CF
3
), 112.2 ꢀm, CF ), 63.1
2
À124.3 ꢀ4F, m, CF
2
),
7.7
8.7
1564, 1457, 1343, 1203, 1157,
1120, 1072, 1028, 960, 874
Calcd. for C
8 10 3
H F10NO P: C, 24.7; H, 2.6; F, 48.8;
3
2
), 1.19
ꢀdt, J ˆ 4, 29, OCH ), 36.7 ꢀd, J ˆ 2, NCH
2
2
),
À83.2 ꢀ6F, m, CF
3
)
N, 3.6. Found: C, 24.6; H, 2.4; F, 48.7; N, 3.6.
ꢀ
3
)
17.7 ꢀd, J ˆ 7, CH
3
)
e ꢀM
w
417) 4.38 ꢀ4H, dt, J ˆ 7, 13, OCH
2
), 3.14 ꢀ4H, dq,
116.5 ꢀtq, J ˆ 36, 287, CF
256, CF
), 62.1 ꢀdt, J ˆ 4, 5, OCH
8.7 ꢀd, J ˆ 4, NCH ), 13.9 ꢀd, J ˆ 2, CH
3
), 111.8 ꢀdq, J ˆ 7,
À124.2 ꢀ4F, m, CF
2
),
1568, 1428, 1378, 1340, 1207,
14 3
Calcd. for C10H F10NO P: C, 28.8; H, 3.6; F, 45.6;
J ˆ 7, 12, NCH ), 1.11 ꢀ6H, d, J ˆ 7, CH
2
3
)
2
2
),
À83.2 ꢀ6F, m, CF
3
)
1163, 1028, 957, 906, 690, 526, 401 N, 3.4. Found: C, 28.9; H, 3.6; F, 45.4; N, 3.1.
3
2
3
)
6
6
6
6
6
a ꢀM
w
461) 4.47 ꢀ4H, m, OCH
475) 4.46 ꢀ4H, m, OCH
2
), 3.52 ꢀ2H, d, J ˆ 6, NH
2
)
107±120 ꢀcomplex m, C
3
F
7
), 62.1
À126.7 ꢀ4F, m, CF
2
), À120.8 ꢀ4F,
8.9
8.9
9.5
8.0
8.9
1560, 1458, 1408, 1356, 1228, 1184, Calcd. for C
8
H
6
F
14NO
3
P: C, 20.8; H, 1.3; F, 57.7;
ꢀ
dt, J ˆ 4, 28, OCH
2
)
m, CF
2
), À80.1 ꢀ6F, t, J ˆ 11, CF
3
)
3
)
3
)
3
)
1126, 1082, 1016, 966, 926, 876
N, 3. Found: C, 20.6; H, 1.2; F, 57.4; N, 2.7.
b ꢀM
w
2
), 3.22 ꢀ1H, m, NH),
108±121 ꢀcomplex m, C
ꢀdt, J ˆ 4, 29, OCH
3
F
7
), 62.4
À126.7 ꢀ4F, m, CF
2
), À120.7 ꢀ4F,
1431, 1356, 1300, 1230, 1186,
1128, 1082, 1016, 966, 928, 872
Calcd. for C
9 8 3
H F14NO P: C, 22.7; H, 1.7; F, 56;
2
.65 ꢀ3H, dd, J ˆ 6, 13, CH
3
)
2
), 27.6 ꢀm, CH
3
)
m, CF
2
), À80.0 ꢀ6F, t, J ˆ 11, CF
N, 2.9. Found: C, 22.7; H, 1.6; F, 55.6; N, 2.8.
c ꢀM
w
489) 4.41 ꢀ4H, m, OCH
2
), 2.72 ꢀ6H, d, J ˆ 11, CH
3
)
108±121 ꢀcomplex m, C
3
F
7
), 61.6
À126.7 ꢀ4F, m, CF
2
), À120.7 ꢀ4F,
1489, 1460, 1408, 1348, 1321, 1228, Calcd. for C10
H
10
F14NO
3
P: C, 24.5; H, 2; F, 54.4;
ꢀ
dd, J ˆ 4, 28, OCH ), 36.3 ꢀd, J ˆ 4, CH
2
3
)
m, CF ), À80.1 ꢀ6F, t, J ˆ 13, CF
2
1186, 1130, 1074, 1007, 966, 926
N, 2.9. Found: C, 24.6; H, 1.9; F, 54.3; N, 2.7.
d ꢀM
w
489) 4.46 ꢀ4H, m, OCH
2
), 3.33 ꢀ1H, m, NH), 3.01 ꢀ2H,
108±121 ꢀcomplex m, C
3
F
7
), 62.3 ꢀdd, J ˆ 3,
À126.7 ꢀ4F, m, CF
2
), À120.7 ꢀ4F,
1460, 1442, 1356, 1230, 1186,
1128, 1082, 1016, 968, 928, 874
Calcd. for C10
10 3
H F14NO P: C, 24.5; H, 2; F, 54.4;
dd, J ˆ 7, 11, CH
2
), 1.18 ꢀ3H, dt, J ˆ 1, 7, CH
), 3.11 ꢀ4H, dq, J ˆ 7,
3
)
28, OCH ), 36.3 ꢀm, CH ), 16.9 ꢀd, J ˆ 7, CH
2
2
3
)
m, CF ), À80.1 ꢀ6F, t, J ˆ 13, CF
2
N, 2.9. Found: C, 24.6; H, 2.1; F, 54.4; N, 2.9.
e ꢀM
w
517) 4.37 ꢀ4H, m, OCH
2
108±120 ꢀcomplex m, C
3
F
7
), 61.9 ꢀdd, J ˆ 4, 28,
À126.7 ꢀ4F, m, CF
2
), À120.6 ꢀ4F,
1458, 1387, 1350, 1228, 1184, 1130, Calcd. for C12
14 3
H F14NO P: C, 27.9; H, 2.7; F, 51.5;
1
3, CH
2
), 1.14 ꢀ6H, t, J ˆ 7, CH
3
)
OCH
2
), 39.8 ꢀd, J ˆ 5, CH
2
), 14.2 ꢀd, J ˆ 7, CH
3
)
m, CF ), À80 ꢀ6F, m, CF
2
3
)
1074, 1039, 1016, 966, 926, 868 N, 2.7. Found: C, 27.8; H, 2.6; F, 51.2; N, 2.6.
a
All mass spectra ꢀchemical ionisation) displayed a prominent molecular ion M ‡ 1 peak.

Table 6
Spectroscopic data for bisꢀfluoroalkyl) phosphoramidates ꢀR
F
O)
2
3
PꢀO)R ꢀNMR data measured in CDCl )
a
1
13
19
31
À1
IR n ꢀcm )
Compound
H NMR d, J ꢀHz)
C NMR d, J ꢀHz)
F NMR d
P NMR d
Elemental analysis ꢀ%)
7
7
7
a ꢀM
w
397)
411)
425)
5.08 ꢀ2H, m, OCH), 3.94
120.1 ꢀdq, J ˆ 5, 288, CF
3
3
), 71.2
), 70.3
À73.9 ꢀ12F, br d, J ˆ 59, CF
3
)
3
)
3
)
9.7
1558, 1458, 1383, 1236, 1207,
1111, 937, 901, 877, 833
Calcd. for C
6 4 3
H F12NO P: C, 18.1; H, 1; F, 57.4;
ꢀ
2H, d, J ˆ 8, NH
2
)
ꢀdsep, J ˆ 4, 35, OCH)
N, 3.5. Found: C, 17.9; H, 0.9; F, 57.3; N, 3.4.
b ꢀM
w
5.2 ꢀ2H, m, OCH), 2.68 ꢀ3H, d,
J ˆ 13, CH ), 2.58 ꢀ1H, m, NH)
121.5 ꢀdq, J ˆ 4, 281, CF
À73.3 ꢀ12F, br d, J ˆ 38, CF
À73.2 ꢀ12F, br d, J ˆ 37, CF
9.5
9.4
1439, 1383, 1358, 1298, 1275,
1205, 1188, 1107, 904, 874
7 6 3
Calcd. for C H F12NO P: C, 20.4; H, 1.5; F, 55.5;
3
ꢀdsep, J ˆ 4, 35, OCH), 27.1 ꢀm, CH
3
)
N, 3.4. Found: C, 20.1; H, 1.3; F, 55.4; N, 3.3.
c ꢀM
w
5.0 ꢀ2H, m, OCH), 2.76
6H, d, J ˆ 11, CH
120.7 ꢀdq, J ˆ 9, 274, CF
3
), 71.4
1489, 1460, 1371, 1329, 1300,
1265, 1234, 1201, 1130, 1113,
8 8 3
Calcd. for C H F12NO P: C, 22.6; H, 1.9; F, 53.6;
ꢀ
3
)
ꢀdsep, J ˆ 4, 31, OCH), 37 ꢀm, CH
3
)
N, 3.3. Found: C, 22.5; H, 1.9; F, 53.3; N, 3.1.
1
090, 1009, 899
7
7
8
8
d ꢀM
w
425)
453)
253)
267)
5.2 ꢀ2H, m, OCH), 3.02 ꢀ2H, m, CH
2
), 2.63
122.2 ꢀddq, J ˆ 4, 282, 290, CF
3
), 70.5
À73.2 ꢀ12F, br d, J ˆ 39, CF
3
)
9.2
9.0
8.7
8.8
1441, 1381, 1294, 1194, 1111,
985, 877
Calcd. for C
8 8 3
H F12NO P: C, 22.6; H, 1.9; F, 53.6;
ꢀ
1H, m, NH), 1.17 ꢀ3H, dd, J ˆ 1, 7, CH
3
)
ꢀm, OCH), 36.1 ꢀm, CH
2
), 17.5 ꢀd, J ˆ 7, CH
3
)
N, 3.3. Found: C, 22.5; H, 1.9; F, 53.3; N, 3.1.
e ꢀM
w
5.03 ꢀ2H, m, OCH), 3.17 ꢀ4H, dq,
J ˆ 7, 13, CH ), 1.18 ꢀ6H, t, J ˆ 7, CH
120.2 ꢀdq, J ˆ 4, 277, CF
3
), 71.5 ꢀdd, J ˆ 4, 36,
3
)
À73.1 ꢀ12F, br d, J ˆ 118, CF
3
)
1469, 1371, 1267, 1201,
1113, 1090, 1039, 968
Calcd. for C10
12 3
H F12NO P: C, 26.5; H, 2.6; F,
2
3
)
OCH), 39.8 ꢀd, J ˆ 4, CH ), 13.7 ꢀd, J ˆ 2, CH
2
50.3; N, 3.1. Found: C, 26.5; H, 2.5; F, 50; N, 2.8.
a ꢀM
w
4.72 ꢀ2H, complex m, OCH), 4.61
2
8H, m, FCH ), 3.34 ꢀ2H, m, NH )
81.9 and 80.4 ꢀdd, J ˆ 9, 183, FCH
2
),
À30.9 ꢀ2F, dt, J ˆ 17, 46, FCH
2
2
),
)
1564, 1460, 1412, 1385, 1244,
1103, 1039, 991, 901
Calcd. for C
6 12 4 3
H F NO P: C, 28.5; H, 4.7; F, 30;
ꢀ
2
73.9 ꢀdt, J ˆ 6, 21, CO)
À30.9 ꢀ2F, dt, J ˆ 19, 46, FCH
N, 5.5. Found: C, 28.5; H, 4.7; F, 29.7; N, 5.3.
b ꢀM
w
4.65 ꢀ2H, complex m, OCH), 4.52
81.9 and 80.4 ꢀdd, J ˆ 9, 183, FCH
2
),
À30.9 ꢀ2F, dt, J ˆ 17, 46, FCH
2
2
),
)
1462, 1427, 1414, 1242, 1103,
1041, 987, 891, 802
7 14 4 3
Calcd. for C H F NO P: C, 31.5; H, 5.2; F, 28.5;
ꢀ
ꢀ
8H, m, FCH ), 2.78 ꢀ1H, m, NH), 2.58
2
73.4 ꢀdt, J ˆ 5, 21, CO), 27.4 ꢀm, NHCH
3
)
À30.9 ꢀ2F, dt, J ˆ 18, 46, FCH
N, 5.2. Found: C, 31; H, 5; F, 28.2; N, 5.1.
3H, d, J ˆ 13, NCH
3
)
8
8
c ꢀM
w
281)
281)
4.7 ꢀ2H, complex m, OCH), 4.56
8H, m, FCH
), 2.70 ꢀ6H, d, J ˆ 11, CH
82.2 and 79.9 ꢀdd, J ˆ 12, 188, FCH
2
),
À48.2 ꢀ2F, dt, J ˆ 17, 46, FCH
2
2
),
)
9.2
7.8
1460, 1412, 1315, 1252, 1190,
1105, 1043, 1001, 903, 876, 804
Calcd. for C
8 16 4 3
H F NO P: C, 34.2; H, 5.7; F, 27;
ꢀ
2
3
)
73.1 ꢀdt, J ˆ 6, 21, CO), 36.1 ꢀd, J ˆ 4, CH
3
)
À46.9 ꢀ2F, dt, J ˆ 18, 46, FCH
N, 5. Found: 34.2; H, 5.6; F, 26.6; N, 4.8.
d ꢀM
w
4.71 ꢀ2H, complex m, OCH), 4.55
8H, m, FCH
), 3.47 ꢀ2H, q, J ˆ 7, NCH
.02 ꢀ1H, m, NH), 1.18 ꢀ3H, t, J ˆ 7, CH
82.0 and 79.9 ꢀdd, J ˆ 10, 177, FCH
2
), 73.1 ꢀdt,
À48.1 ꢀ2F, dt, J ˆ 19, 46, FCH
2
2
),
)
1639, 1460, 1439, 1383, 1360, 1242,
1107, 1043, 987, 903, 879, 802
8 16 4 3
Calcd. for C H F NO P: C, 34.2; H, 5.7; F, 27;
ꢀ
2
2
),
J ˆ 6, 21, CO), 36.2 ꢀs, CH ), 16.6 ꢀd, J ˆ 7, CH
2
3
)
À46.9 ꢀ2F, dt, J ˆ 21, 48, FCH
N, 5. Found: C, 34.1; H, 5.5; F, 26.6; N, 4.8.
3
3
)
8
e ꢀM
w
309)
4.71 ꢀ2H, complex m, OCH), 4.56
8H, m, FCH ), 3.12 ꢀ4H, dt,
J ˆ 7, 12, NCH ), 1.12 ꢀ6H, t, J ˆ 7, CH
82.1 and 79.9 ꢀdd, J ˆ 10, 177, FCH
2
), 72.9 ꢀdt, J ˆ 6, À48.3 ꢀ2F, dt, J ˆ 16, 46, FCH
2
2
),
)
8.8
1466, 1385, 1300, 1255, 1213,
1176, 1105, 1039, 970, 901, 874
Calcd. for C10
20 4 3
H F NO P: C, 38.8; H, 6.5; F, 24.6;
ꢀ
2
21, CO), 39.4 ꢀd, J ˆ 4, CH ), 13.5 ꢀd, J ˆ 2, CH
2
3
)
À46.9 ꢀ2F, dt, J ˆ 19, 45, FCH
N, 4.5. Found: C, 38.7; H, 6.5; F, 24.5; N, 4.3.
2
3
)
9
9
a ꢀM
w
317)
331)
3.1 ꢀ2H, s, NH ), 1.7 ꢀ12H, d, J ˆ 16, CH
2
3
)
125.5 ꢀdq, J ˆ 10, 289, CF
3
), 80.4
À83.2 ꢀ6F, m, CF
3
3
)
)
À0.9
À0.7
1568, 1475, 1398, 1335, 1246,
1165, 1130, 1003, 931, 908, 810
Calcd. for C
8 14 6 3
H F NO P: C, 30.3; H, 4.4; F, 36;
ꢀ
dq, J ˆ 5, 31, CO), 20.9 ꢀm, CH
3
)
N, 4.4. Found: C, 30.1; H, 4.4; F, 35.5; N, 4.2.
b ꢀM
w
2.94 ꢀ1H, s, NH), 2.5 ꢀ3H, dd,
J ˆ 6, 13, CH ), 1.58 ꢀ12H, d, J ˆ 6, CH
124.9 ꢀdq, J ˆ 13, 283, CF
3
), 80.5 ꢀdq, J ˆ 6,
), 21.3 ꢀm, CH
À83.9 ꢀ6F, m, CF
1478, 1460, 1425, 1397, 1378,
1333, 1249, 1231, 1164, 1143,
9 16 6 3
Calcd. for C H F NO P: C, 32.6; H, 4.8; F, 34.4;
3
3
)
30, CO), 27.1 ꢀd, J ˆ 2, CH
3
3
)
N, 4.2. Found: C, 32.5; H, 4.6; F, 34.2; N, 4.1.
1
108, 1035, 1002, 932, 911
9
9
c ꢀM
w
345)
345)
2.64 ꢀ6H, d, J ˆ 11, NCH
3
), 1.64 ꢀ12H,
122.2 ꢀdq, J ˆ 13, 278, CF
3
), 77.4 ꢀdq, J ˆ 6,
3
)
À83.3 ꢀ6F, m, CF
3
3
)
)
À0.3
À1.7
1475, 1398, 1335, 1267, 1167,
1130, 997, 928, 804
Calcd. for C10
18 6 3
H F NO P: C, 34.8; H, 5.2; F, 33;
d, J ˆ 7, CH
3
)
31, CO), 32.9 ꢀm, CH
3
), 18.4 ꢀd, J ˆ 51, NCH
N, 4.1. Found: C, 34.8; H, 5.1; F, 33.1; N, 4.
d ꢀM
w
2.94 ꢀ4H, dq, J ˆ 7, 11, NCH
2
), 1.68 ꢀ12H,
124.9 ꢀdq, J ˆ 13, 286, CF
3
), 80.8
À83.3 ꢀ6F, m, CF
1604, 1458, 1425, 1396, 1377,
1333, 1284, 1244, 1163, 1142,
1001, 964, 926, 858
18 6 3
Calcd. for C10H F NO P: C, 34.8; H, 5.2; F, 33;
d, J ˆ 11, CH ), 1.13 ꢀ6H, dt, J ˆ 1, 7, CH
3
3
)
ꢀdq, J ˆ 5, 31, CO), 36.6 ꢀm, NCH
2
),
N, 4.1. Found: C, 34.5; H, 5.1; F, 32.9; N, 3.9.
2
1.4 ꢀd, J ˆ 29, CH ), 16.4 ꢀd, J ˆ 7, CH
3
3
)
a
All mass spectra ꢀchemical ionisation) displayed a prominent molecular ion M ‡ 1 peak.

118
C.M. Timperley et al. / Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
Table 7
PꢀO)NMe under identical conditions remained intact [7].
2
2 2
Mp data for dialkyl phosphoramidates of structure ꢀRO) PꢀO)NH
The contrast in reactivity is due to electronic differences
Group
Ethyl
Compound
R
Mp ꢀ8C)
References
between the two phosphoramidates. It was of interest to
examine the effect of replacing the dimethylamino group
with the less electron-donating amino group ꢀthis should
retard hydrolysis). Treatment of diethyl phosphoramidate
and bisꢀtri¯uoroethyl) phosphoramidate 4 with two molar
equivalents of HCl gave, after 5 days at room temperature,
low conversion to the phosphorochloridates.
4
CF
3
CH
CH
2
42±43
50±51
±
CH
3
2
[16]
Propyl
5a
7a
9a
C
C
2
2
F
5
CH
CH
2
35
±
H
5
2
39±42
[17]
Isopropyl
t-Butyl
ꢀCF
CH
3
)
2
CH
CH
32±33
56±57
±
[16]
ꢀ
3
)
2
ꢀCH
CH
3
)
)
2
CF
3
CO
CO
148
122±125
±
ꢀ
3
2
CH
3
[18]
un¯uorinated counterparts, phosphoramidate 9a melts at a
higher temperature than its counterpart ꢀTable 7). Factors
affecting the mps of ¯uorinated phosphoramidates are the
size of the ¯uoro-ester groups, which affect packing in the
solid state, and hydrogen-¯uorine bonding ꢀintermolecular
associations between C±F. . .H±C or C±F. . .H±N are only
vaguely understood).
It follows from these experiments and previous ones [7]
that the reaction of phosphoramidates with hydrogen chlor-
ide depends greatly on the groups on the phosphorus and
nitrogen atoms. The substituents on phosphorus may be
placed in the following sequence CH3CH2O > CF3CH2O,
while those on nitrogen may be placed in the order Me > H,
according to their ability to facilitate hydrolysis. As a
general rule, electron-withdrawing groups on either phos-
phorus or nitrogen reduce the basicity of the nitrogen atom
and suppress acidolysis.
The relationship between bp and amido groups is clear,
the bp decreasing in the order ±NH > NHR > NR due to
intermolecular hydrogen bonding, as noted before [15].
2
2
2
.5. Acid hydrolysis studies
In phosphoramidates, overlap of the p-p electrons of
nitrogen with the vacant d orbitals of phosphorus produces
complex bonding. Electron-donating alkyl substituents such
as ethyl groups favour resonance hybrid D. Electron-with-
drawing alkyl substituents such as tri¯uoroethyl groups
favour resonance hybrid E; here increased back-bonding
from the lone pair on nitrogen reduces its basicity, explain-
ing the easier acid hydrolysis of ꢀCH CH O) PꢀO)NMe
2.6. The behaviour of bisꢀtrifluoroethyl)
phosphoramidate to selected electrophiles
Dialkyl phosphoramidates react with oxalyl chloride in
the presence of base, e.g. pyridine or triethylamine, to give
phosphoroisocyanidates F [20,21]. They also react with
thionyl chloride to give phosphoroꢀthionylamidates) G [22].
3
2
2
2
compared to ꢀCF CH O) PꢀO)NMe [7].
3
2
2
2
Phosphoramidates ꢀRO) PꢀO)NR sometimes react with
2
2
an excess of anhydrous hydrogen chloride to form dialkyl
phosphorochloridates ꢀRO) PꢀO)Cl [19]. The mechanism
2
initially involves protonation of the amino function. Attack
by chloride ion on the phosphorus atom then liberates
ammonia which is intercepted by extra hydrogen chloride.
Ammonium chloride precipitates from the reaction mixture
and ensures that the process is irreversible. Earlier we
showed that ꢀEtO) PꢀO)NMe underwent 87% conversion
Compared to their un¯uorinated analogues, bisꢀ¯uor-
oalkyl) phosphoramidates contain a much less nucleophilic
amino group for reasons already discussed. We decided to
check if the amino group was suf®ciently nucleophilic to
combine with oxalyl or thionyl chloride. Prolonged heating
of amidate 4 with oxalyl chloride in chloroform gave
bisꢀtri¯uoroethyl) phosphoroisocyanidate 10. It was isolated
2
2
to ꢀEtO) PꢀO)Cl in 5 days at room temperature when treated
2
with two molar equivalents of HCl in ether; ꢀCF CH O)
2-
3
2

C.M. Timperley et al. / Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
119
in low yield as a colourless liquid ꢀbp 34 8C/0.02 mmHg).
The infrared spectrum exhibited bands at 2293 cm for
À1
À1
stretching of the NCO group, at 1423±1500 cm for its
À1
symmetrical vibration, and at 574 cm for its deformation
À1
[
23]. The C=O stretch appeared at 1712 cm
.
The N-methoxyphosphoramidate is an unusual phos-
phorus compound and the ®rst such ¯uorinated species.
The un¯uorinated equivalents are little known. Two reports
claim that diethyl N-methoxyphosphoramidate [27] and
diphenyl N-methoxyphosphoramidate [28] can be prepared
by Todd±Atherton reaction of the corresponding phosphite
with O-methylhydroxylamine. A phase-transfer modi®ca-
tion, using methylhydroxylamine hydrochloride, has also
been used to obtain ꢀCH CH O)PꢀO)NHOCH in 78% yield
The analogous reaction with thionyl chloride did not
occur, further con®rming the deactivating effect of ¯uoro-
ester groups on nucleophilic sites attached to phosphorus.
3
2
3
[29]. This, like the ¯uoro-analogue 11, is a colourless liquid
that is stable at room temperature.
2.7. Reaction of bisꢀtrifluoroethyl) phosphorochloridate
with methoxyamine in a two-phase system
2.8. Reaction of bisꢀtrifluoroethyl) phosphorochloridate
with sodium azide
While exploring the chemistry of bisꢀ¯uoroalkyl) phos-
phorochloridates, it became evident they phosphorylate
amines more readily than alcohols or thiols. This is in
accord with the known behaviour of dialkyl phosphorochlor-
idates towards nucleophiles where the selectivity of phos-
phorylation decreases in the order RNH2 > ROH > RSH.
With primary amines, N-phosphorylation can take place
exclusively in the presence of a primary alcohol [24,25].
It might be possible for organic solutions of dialkyl phos-
phorochloridates to react with aqueous solutions of nitrogen
nucleophiles, and this would be of great utility. However, this
process is not used much as dialkyl phosphorochloridates
are reasonably water-soluble and often easily hydrolysed
The ®rst phosphorus acid azides were described in 1954
by Schrader [30] and Hartley and Pound [31]. Unlike other
organic azides, they are often relatively stable [32]. Diethyl
phosphorazidate ꢀCH CH O) PꢀO)N , a distillable liquid
3
2
2
3
made by heating a solution of diethyl phosphorochloridate
with sodium azide in acetone, was reported in 1967 by Scott
et al. [33]. We found that reaction of bisꢀtri¯uoroethyl)
phosphorochloridate with sodium azide in acetonitrile was
complete after 3 h at room temperature. The phosphorazi-
date 13, the ®rst example of such a species, was isolated after
®ltration and removal of solvent as a mobile colourless
liquid. It was 97% pure by NMR and gas chromatogra-
phy±mass spectrometry ꢀGC±MS) analyses. Distillation was
not attempted for fear of explosion.
to phosphoric acids ꢀRO) PꢀO)OH and/or pyrophosphates
2
ꢀRO) PꢀO)OPꢀO)ꢀOR) . The latter can be appreciably toxic
2 2
and their accidental formation is best avoided.
The use of bisꢀ¯uoroalkyl) phosphorochloridates may be
more interesting for two reasons. Poly¯uorinated ester
groups shield such molecules from attack by water, and if
hydrolysis does occur, only the acids ꢀR O) PꢀO)OH will
F
2
form [6]; pyrophosphates of structure ꢀR O) PꢀO)O-
2
F
PꢀO)ꢀOR ) are not yet known and are unlikely to be stable
F 2
The infrared spectrum of azidate 13 showed a strong azide
À1
to moisture. Such reasoning led us to examine a model
two-phase system. Treatment of aqueous O-methylhydro-
xylamine with bisꢀtri¯uoroethyl) phosphorochloridate in
chloroform produced a 9:1 mixture of phosphorylated
product 11 and trisꢀtri¯uoroethyl) phosphate 12; the identity
of the latter, whose formation is dif®cult to rationalise, was
con®rmed by comparison of its analytical data with those of
an authentic specimen [26]. The mixture could not be
puri®ed by distillation as both products co-distilled.
stretch at 2182 cm . The usual range for un¯uorinated
À1
phosphoryl azides is 2138±2195 cm
stretch for diethyl phosphorazidate appears at 2140 cm
[32]. The azide
À1
À1
[33]. The large difference of 42 cm between the stretches
of the ¯uoro and hydrocarbon analogues is due the much
greater electronegativity of the ꢀCF CH O) PꢀO)-fragment.
In the chemical ionisation mass spectrum of compound 13, a
3
2
2
‡
major ion [ꢀCF CH O) PO] is observed at m/z 245, arising
3
2
2
from loss of the azide group.

120
C.M. Timperley et al. / Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
3
. Conclusion
Caution: although no safety problems were encountered
during work with methoxyamine hydrochloride or sodium
azide, precautions against possible explosions should be
implemented when handling the solids, their solutions,
and the phosphorus derivatives. A plastic spatula was used
when handling sodium azide. The phosphorus compounds
may have anticholinesterase activity and should be manipu-
lated with care.
Bisꢀ¯uoroalkyl) phosphorochloridates are highly reactive
towards ammonia and primary and secondary aliphatic
amines. A range of new bisꢀ¯uoroalkyl) phosphoramidates
have been obtained whose properties remain largely unex-
plored. Their nitrogen basicity and nucleophilicity is lower
than that of un¯uorinated phosphoramidates. The chlorine
atom of bisꢀ¯uoroalkyl) phosphorochloridates is displaced
by O-alkylhydroxylamines in a water-chloroform system
and this approach may prove useful for substitutions where
the nitrogen nucleophile is best handled as a salt. The
chemistry of the produced bisꢀ¯uoroalkyl) N-alkoxypho-
sphoramidates ꢀR O) PꢀO)NHOR awaits exploration. They
4.1. Reactions with ammonia
This general procedure is illustrated for the synthesis of
bisꢀ2,2,2-tri¯uoroethyl) phosphoramidate 4. A round-bot-
tomed ¯ask was equipped with a T-adaptor and a dry ice
condenser whose outlet was ®tted with a guard tube contain-
ing anhydrous calcium chloride. The ¯ask was charged with
a solution of bisꢀ2,2,2-tri¯uoroethyl) phosphorochloridate
ꢀ10 g, 35.7 mmol) in ether ꢀ50 ml). The ¯ask and the con-
denser were cooled to À78 8C ꢀdry ice-acetone) and ammo-
nia gas was passed through the T-adaptor and allowed to
condense into the solution. An instant precipitate of ammo-
nium chloride was observed. Lique®ed ammonia was
allowed to drop into the reaction mixture until it was clear
that more than two molar equivalents had been added. The
ammonia supply was turned off and the ¯ask allowed to
warm to room temperature ꢀthe condenser containing dry ice
remained at À78 8C). Once the ¯ask reached room tem-
perature, the dry ice in the cold ®nger was allowed to
evaporate. The reaction mixture was left to stand for 2 h.
The precipitate was ®ltered off and the ®ltrate concentrated
to yield bisꢀ2,2,2-tri¯uoroethyl) phosphoramidate 4 as a
white crystalline solid ꢀ8.5 g, 91%); mp 42±43 8C. Multi-
nuclear NMR analysis indicated 99% purity. In other cases,
concentration of the ®ltrate gave a liquid that was puri®ed by
bulb-to-bulb distillation under reduced pressure.
F
2
should undergo some reactions characteristic of un¯uori-
nated analogues, e.g. conversion to N-alkoxy-N-chloropho-
sphoramidates ꢀRO) PꢀO)NꢀCl)OR by chlorination [29].
2
The chlorine atom of bisꢀ¯uoroalkyl) phosphorochloridates
is also replaced by azide ion. Nothing is known about the
chemistry of the produced phosphorazidates ꢀR O) PꢀO)N .
F
2
3
By analogy with their un¯uorinated counterparts [32], they
should be capable of a range of useful transformations.
These might include addition of trivalent phosphorus
reagents ꢀthe Staudinger reaction), nucleophilic substitu-
tions where the azide behaves as a pseudohalogen, photo-
lysis to generate the nitrene, and reactions with unsaturated
compounds ꢀ1,3-dipolar cycloadditions). Research along
these lines will surely lead to some interesting and novel
phosphorus chemistry.
4
. Experimental details
Bisꢀ¯uoroalkyl) phosphorochloridates were obtained in
high purity using previously reported chemistry [1]. Diethyl
phosphoramidate was purchased from Aldrich ꢀGillingham,
UK). All reagents were of commerical quality and were used
without extra puri®cation. Anhydrous solvents were used for
4.2. Reactions with methylamine and ethylamine
reactions. NMR spectra were obtained on a JEOL Lambda
1
These were conducted as described in the previous section
but on a smaller scale: bisꢀ¯uoroalkyl) phosphorochloridate
ꢀ5 mmol) in ether ꢀ20 ml). After ®ltration, concentration of
the ®ltrate gave solid or liquid products. The solids were
found to be very pure and did not require recrystallisation
ꢀthis would have only lowered the yields). Liquids were
puri®ed by bulb-to-bulb distillation under reduced pressure.
5
00 instrument ꢀoperating at 500 MHz for H, 125 MHz for
1
3C, 470 MHz for 19F, and 202 MHz for 31P spectra) or a
JEOL Lambda 300 instrument ꢀoperating at 300 MHz for
1
H, 75 MHz for 13C, 282 MHz for 19F, and 121.5 MHz for
3
1
P spectra) as solutions in CDCl , with internal reference
3
SiMe for H and C, external CFCl for 19F and external
MeO) P ꢀd: 140 ppm) for 31P spectra. Data are recorded as
1
13
4
3
ꢀ
3
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: broad;
coupling constant ꢀJ, Hz) and assignment. IR spectra were
recorded as liquid ®lms on a Nicolet SP210 instrument
using Omnic software. Reaction mixtures were monitored
by GC±MS using a Finnigan MAT GCQ instrument with
chemical ionisation ꢀCI) using methane as reagent gas. Mws
of pure products were con®rmed with methane ‡ve CI data
4.3. Reactions with dimethylamine and diethylamine
An excess of chilled dimethylamine was pipetted into a
stirred solution of the appropriate bisꢀ¯uoroalkyl) phosphor-
ochloridate ꢀ5 mmol) in ether ꢀ50 ml) at 0±5 8C. After
addition, the mixture was kept at this temperature for a
further 30 min, then allowed to warm to room temperature;
excess dimethylamine evaporated. After 2 h, the precipitated
amine hydrochloride salt was removed by ®ltration. Con-
centration of the ®ltrate and bulb-to-bulb distillation of the
ꢀ
70 eV).

C.M. Timperley et al. / Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
121
residue under reduced pressure gave bisꢀ¯uoroalkyl) N,N-
dimethylphosphoramidates as colourless liquids. Similarly,
the addition of two molar equivalents of diethylamine
4.6. Synthesis of bisꢀ2,2,2-trifluoroethyl) N-
methoxyphosphoramidate ꢀ11)
ꢀ
ꢀ
10 mmol) in ether ꢀ10 ml) to the phosphorochloridate
5 mmol) in ether ꢀ50 ml), and work-up as described above,
A solution of bisꢀ2,2,2-tri¯uoroethyl) phosphorochlori-
date ꢀ2 g, 7.14 mmol) in CHCl ꢀ10 ml) was added in one
3
gave bisꢀ¯uoroalkyl) N,N-diethylphosphoramidates as col-
ourless liquids or white solids. The chloridate [ꢀCH ) -
portion to a solution of O-methylhydroxylamine hydrochor-
ide ꢀ0.66 g, 7.85 mmol) and sodium hydroxide ꢀ0.63 g,
3
2
CF CO] PꢀO)Cl did not react with diethylamine in ether
3
15.71 mmol) in H O ꢀ10 ml). The two-phase mixture was
2
2
even when heated under re¯ux for 14 h in the presence of a
small amount of 4-dimethylaminopyridine.
stirred vigorously for 3 h. The organic layer was separated,
washed with water ꢀ2 Â 20 ml), dried over Na SO , ®ltered
2
4
and the ®ltrate concentrated. Bulb-to-bulb distillation of the
residue gave a mobile colourless liquid ꢀ1.3 g). Multinuclear
NMR and mass spectral analyses showed it to be a 1:9
mixture of trisꢀtri¯uoroethyl) phosphate ꢀCF CH O) P=O
4.4. Reactivities of diethyl phosphoramidate and bisꢀ2,2,2-
trifluoroethyl) phosphoramidate to hydrogen chloride
3
2
3
A solution of methanol ꢀ0.32 g, 10 mmol) and acetyl
chloride ꢀ0.79 g, 10 mmol) in ether ꢀ10 ml) was added
drop-wise by cannula to a stirred solution of the phosphor-
amidate ꢀ5 mmol) in ether ꢀ25 ml) at 0±5 8C. After addition,
the mixture was allowed to warm to room temperature and
left to stand. Some ammonium chloride precipitated; its
amount increased slowly over time. The reaction was mon-
itored by GC±MS after 2 h and after 5 days. No product
was observed after 2 h, but 12% ꢀCH CH O) PꢀO)Cl and
and the title compound. The latter has the following spectro-
1
scopic data: H NMR: d ˆ 7:4 ꢀ1H, br s, NH), 4.4 ꢀ4H,
1
3
complex m, OCH ), 3.7 ꢀ3H, s, OCH ). C NMR: d ˆ 122:7
2
3
ꢀdq, J ˆ 10 and 277 Hz, CF ), 65.2 ꢀd, J ˆ 5, OCH ), 63.5
3
3
1
9
ꢀdq, J ˆ 4 and 38 Hz, OCH ). F NMR: d ˆ À74:5 ꢀ6F, t,
2
3
1
J ˆ 9 Hz, CF ). P NMR: d ˆ 6:1. CIMS m/z ꢀrel. int.): 292
3
‡
‡
[M ‡ 1] ꢀ100), 272 [M À F] ꢀ18).
4.7. Synthesis of bisꢀ2,2,2-trifluoroethyl)
phosphorazidate ꢀ13)
3
2
2
4
% ꢀCF CH O) PꢀO)Cl had formed after 5 days. The only
2
3
2
other materials detected were the unchanged phosphor-
amidates.
Finely-divided sodium azide ꢀ0.93 g, 14.28 mmol) was
added in one portion to a stirred solution of bisꢀ2,2,2-
tri¯uoroethyl) phosphorochloridate ꢀ2 g, 7.14 mmol) in
acetonitrile ꢀ30 ml). The suspension was stirred briskly
for 3 h. The solids were removed by ®ltration and the ®ltrate
concentrated to a liquid that still contained a small amount of
solid. Further precipitation of solid was induced by the
addition of diethyl ether ꢀ5 ml). Passage of the resulting
solution through a Pasteur pipette containing a small plug of
glass wool, and removal of solvent and drying under high
vacuum, gave the title compound as a mobile colourless oil
ꢀ1.8 g, 88%). It was shown to be 97% pure by multinuclear
4.5. Synthesis of bisꢀ2,2,2-trifluoroethyl)
phosphoroisocyanidate ꢀ10)
Oxalyl chloride ꢀ0.76 g, 6 mmol) in chloroform ꢀ25 ml)
was added drop-wise to a stirred solution of bisꢀ2,2,2-
tri¯uoroethyl) phosphoramidate ꢀ1.68 g, 6 mmol) in chloro-
form ꢀ30 ml) at 0±5 8C. After addition, the mixture was
allowed to warm to room temperature and left to stand for
1
4 h. The mixture was heated under re¯ux for a further 14 h
and the progress of the reaction monitored by GC±MS. After
this time, it was evident that the reaction would not progress
beyond 76% completion. The solvent was removed. Dis-
tillation of the residue in a Kugelrohr apparatus gave the title
1
NMR and mass spectral analyses. H NMR: d ˆ 4:5 ꢀ4H,
1
3
qdd, J ˆ 2:1, 7.6 and 15.3 Hz, OCH ). C NMR: d ˆ 121:6
2
ꢀdq, J ˆ 9 and 277 Hz, CF ), 64.1 ꢀdq, J ˆ 5 and 39 Hz,
3
1
9
31
compound as a moisture-sensitive colourless liquid ꢀ0.17 g,
1
OCH ). F NMR: d ˆ À74:4 ꢀ6F, br m, CF ). P NMR:
2
3
1
0%). Bp 34 8C/0.02 mmHg. H NMR: d ˆ 4:46 ꢀ4H, qdd,
d ˆ À1:3. IR ꢀ®lm): n ˆ 2182 ꢀN ), 1457, 1422, 1285
3
13
J ˆ 2, 8 and 15 Hz, OCH ). C NMR: d ˆ 125:1 ꢀvery
ꢀP=O), 1175, 1102, 1075, 964, 898, 842, 764, 660, 600,
2
À1
‡
weak m, NCO), 122.4 ꢀdq, J ˆ 9 and 277 Hz, CF ), 64.2 ꢀdq,
559 cm . CIMS m/z ꢀrel. int.): 288 [M ‡ 1] ꢀ100), 268
‡ ‡
3
4 4
3
19
J ˆ 4 and 39 Hz, OCH ). F NMR: d ˆ À74:9 ꢀ6F, m,
[M À F] ꢀ20), 245 [M À N ] ꢀ10). Calcd. for C H -
6 3 3
2
3
1
CF ). P NMR: d ˆ À13:3. IR ꢀ®lm): n ˆ 3122, 2293, 1712
F N O P: C, 16.7; H, 1.4; F, 39.7; N, 14.6. Found: C,
16.6; H, 1.2; F, 39.7; N, 14.6%.
3
ꢀ
9
ꢀ
C=O), 1500, 1423, 1294 ꢀP=O), 1255, 1174, 1093, 964,
28, 844, 654, 574 cm . CIMS m/z ꢀrel. int.): 288 [M ‡ 1]
À1
‡
‡
100), 268 [M À F] ꢀ22). Calcd. for C H F NO P: C, 20.9;
5
4
6
4
H, 1.4; F, 39.7; N, 4.9. Found: C, 20.9; H, 1.4; F, 39.8; N,
.9%.
An analogous procedure using thionyl chloride in place of
4
Acknowledgements
oxalyl chloride was unsuccessful; no conversion to the
desired phosphoroꢀthionylamidate) was detected by GC±
MS even after heating the reaction mixture under re¯ux for
The authors thank Stuart Brewer and Colin Willis for their
interest in this work and Hubert Barucki for translating
reference 19 into English. We also wish to thank the Ministry
of Defence UK for ®nancial support.
1
6 h.

1
22
C.M. Timperley et al. / Journal of Fluorine Chemistry 113 ꢀ2002) 111±122
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