α-haloenamines as reagents for the conversion of phosphorus oxyacids to their halogenated analogues

Article abstract of DOI:10.1055/s-2005-865363

Phosphorus oxyacids are converted to their halogenated analogues under mild conditions. α-Haloenamines are shown to be effective halogen transfer reagents affording good to high yields of the desired products at reaction times, in some cases, less than one minute. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865363

PAPER
1765
a-Haloenamines as Reagents for the Conversion of Phosphorus Oxyacids to
Their Halogenated Analogues
H
alides of Phosp
i
O
k
xyacids Prep
a
ared with
r
a
-Haloen
d
amine
s
Norlin,* Lars Juhlin, Per Lind, Lars Trogen
Swedish Defence Research Agency, Division of NBC-Defence, Department of Threat Assessment, Cementvägen 20, 90182 Umeå, Sweden
Fax +46(90)106809; E-mail: rikard.norlin@foi.se
Received 12 January 2005
sized without using the chloro compounds as intermedi-
Abstract: Phosphorus oxyacids are converted to their halogenated
ates, which is the case in most methods for their
preparation. Care must be taken in handling these com-
analogues under mild conditions. a-Haloenamines are shown to be
effective halogen transfer reagents affording good to high yields of
pounds, especially the phosphonofluoridates. They are
highly toxic and will damage the nervous system if ex-
posed to the substances.
the desired products at reaction times, in some cases, less than one
minute.
Key words: phosphorus, a-haloenamines, halogenation, fluorine,
chlorine
Introduction of halogen on to phosphorus is a central as-
pect of phosphorus chemistry. Phosphorus halides are im-
portant intermediates in for instance medicinal,1
polymer,2 and pesticide chemistry3 as well as in oligonu-
cleotide synthesis.4 Classical procedures for the prepara-
tion of phosphorus halides are, in general, performed
under harsh conditions producing corrosive and toxic
byproducts such as HCl and SO2.The recent development
of new, more selective methods has been slow. In the
present work we have investigated the potential of a-ha-
loenamines as reagents for the transfer of halogen (Cl and
F) to phosphorus (Equation 1).
Equation 1 General equation for the conversion of phosphorus
oxyacids (X = Cl or F)
During chlorination the phosphonic acids, unlike carbox-
ylic acids, readily form pyrophosphonates (i.e., the ana-
logues of carboxylic anhydrides). To prevent the
formation of substantial amounts of pyrophosphonate the
halide released in the initial reaction step has to compete
successfully with remaining nucleophilic phosphonic ac-
id. Every molecule of pyrophosphate formed in this way
will reduce the highest possible yield of the desired prod-
uct with two units. The phosphonic acids 2a–10a
(Table 1) were added to the halo enamine in CHCl3 at 50
°C. Higher temperatures did not improve the outcome of
the reaction and addition of the phosphonic acid at a lower
temperature was inferior with respect to the yield of de-
sired product. If, for instance, the reaction mixture was
cooled to 0 °C before addition of the reactant, as suggest-
ed by others,9 a quantitative yield of the corresponding py-
rophosphonate was obtained.
a-Haloenamines have successfully been used for the con-
version of alcohols to alkyl halides5 and of carboxylic ac-
ids to their halides6 as well as for coupling reactions.7 To
the best of our knowledge they have not been investigated
in their ability to transform phosphorus oxyacids into the
corresponding halides. The a-haloenamines do not give
rise to HCl gas or water during the reaction but simply re-
vert to the stable amide from which they are prepared and
which of course is recyclable. Indeed our results prove the
a-haloenamines to be very efficient reagents which react
fast at mild conditions to produce the desired products.
Yields are usually high and few impurities are formed.
The method is applicable to all types of phosphorus oxy-
acids i.e. phosphinic, phosphonic, and phosphoric acids.
Furthermore it is compatible with a variety of functional
groups. The phosphorus oxyacids that were converted to
their halogenated counterparts in this study are given in
Table 1. The phosphonic acids 2a–10a, except for ethyl
methylphosphonic acid (3a), were all synthesized by the
method described in the experimental section8 while the
rest of the starting materials were commercially available.
The fluoro analogues may, with this reagent, be synthe-
In the case of the phosphinic acid 1a (Table 1) the temper-
ature could be slightly lowered but the reaction turned out
just as well at 50 °C.
As predicted the phosphoric acids 11a–12a (Table 1)
were less reactive and consequently produced lower
yields at longer reaction times. To overcome this problem,
the temperature had to be raised significantly, which ex-
cluded CHCl3 as solvent. Among the investigated solvents
were chlorobenzene, tetrachloroethylene, dichloroethane,
dioxane, toluene and benzene. This clearly indicated the
chlorinated solvents to be the better ones which also Ernst
et al10 found in their studies. Tetrachloroethane finally
proved to be the best alternative, giving yields as high as
SYNTHESIS 2005, No. 11, pp 1765–1770
x
x.
x
x
.
2
0
0
5
Advanced online publication: 02.05.2005
DOI: 10.1055/s-2005-865363; Art ID: P00605SS
© Georg Thieme Verlag Stuttgart · New York

1766
R. Norlin et al.
PAPER
Table 1 Phosphorus Oxyacids Converted to the Corresponding Halides
Compound Starting material phosphorus oxyacids Yield of chlorides of phosphorus oxyacids Yield of fluorides of phosphorus oxyacids
(a)
(b) (%)a OH → Cl
(c) (%)a OH → F
1
88
98
2b
86
90
Quant.
81
3
4
81
95
87
77
5c
6
91
75
7
8
80
86
98
79
9c
87
94
81
86
10
11
12
95
57
22
52
a Yields calculated from 31P NMR.
b Both OH groups were converted.
c Compound 5a and 9a were synthesized from L-menthol.
Synthesis 2005, No. 11, 1765–1770 © Thieme Stuttgart · New York

PAPER
Halides of Phosphorous Oxyacids Prepared with a-Haloenamines
1767
95%, due to the possibility of applying a higher reaction reagent was another factor that made us abandon the use
temperature. For diphenylphosphoric acid (12a; Table 1) of haloenamines as solid phase reagents.
we were unable to find reaction conditions producing sat-
isfactory yields. Only 57% product was obtained at 120
All NMR spectra were recorded on a Bruker Avance 500 spectro-
°C in tetrachloroethane. Higher temperatures were not ap-
plicable since the boiling point of the enamine, 130 °C,
constitutes a practical limit unless pressurized equipment
is considered, which was not done due to the toxicity of
the compounds studied. N-(1-Chloro-2-methylprop-1-
enyl)-N,N-diisopropylamine was evaluated as an alterna-
tive a-haloenamine due to the higher boiling point but
proved to be less effective.
meter. EIMS spectra were run on a Hewlett-Packard 5972 MSD and
CIMS spectra were recorded on an Agilent 5973N MSD. From the
mass spectra the ten most significant peaks are reported and in the
cases where the molecular ion is present even though it is not among
the ten largest peaks, it is also reported. For novel compounds and
compounds without satisfactory references full identification is pre-
sented; for the other compounds references are given. All solvents
and glassware were carefully dried before use and the reactions
were run under an Ar atmosphere.
1-Fluoro-N,N,2-trimethyl-1-propenylamine (13) was not
commercially available, which is why it had to be synthe-
sized. Only one publication11 on the synthesis of fluoro-
enamines was found in the literature. Later articles12 refer
to the method given, which appeared to be improved by
the use of CsF instead of KF as originally reported. Ex-
tremely anhydrous conditions were found necessary for
the synthesis that could be significantly facilitated by the
use of a glove box. With the fluoroenamine 13, pyrophos-
phonate formation was less pronounced. On the other
hand over-fluorination occurred to some extent in several
cases. Interestingly the formation of phosphonic difluo-
ride was not dependent on the amount of reagent used or
the reaction time and is hence a competitive reaction rath-
er than a reaction of the desired product. The mechanism
of this reaction has not been fully investigated and clari-
fied. Even though the two side reactions could be individ-
ually minimized by changing the temperature, raising the
temperature increased the amount of difluoride and low-
ering the temperature increased the amount of pyrophos-
phonate. These problems did of course affect the yields,
which were lower than for most of the chloro compounds.
However compounds that could not be fluorinated twice
(Table 1, entry 1) or were intended to be doubly fluorinat-
ed (Table 1, entry 2) afforded excellent yields that were
slightly better than those of their chloro analogues. The
largest difference between the chloro and fluoro counter-
parts was obtained with dibutyl phosphoric acid (11a;
Table 1) which produced a 95% yield of the chloro com-
pound 11b but only 22% of the fluoro analogue 11c.
Phosphonic Acids 3a–10a; General Procedure
To a solution of methylphosphonic dichloride (1 g, 7.5 mmol) in an-
hyd toluene (10 mL) water (0.136 mL, 1 equiv) was added under
vigorous stirring. After 2 h neopentyl alcohol (0.67 g, 7.5 mmol)
was added and the mixture heated, at first to 100 °C and after a
while, to 110 °C for 2.5 h. The solvent was evaporated yielding the
crude product (1.3 g, quant.). If further purification was desired the
crude product was dissolved in EtOAc (15 mL) and extracted with
sat. NaHCO3 followed by acidification with 2 M HCl and back ex-
traction with EtOAc. The yield was substantially lowered but the
purity was excellent. Note that isomeric pure L-menthol was used in
the synthesis of compounds 5a and 9a.
Dimethylphosphinic Chloride (1b)
The reaction procedure was the same as that used for the phospho-
nochloridates (see below) and the reaction was completed within 1
min with a yield of 88%.
1H NMR (500 MHz, CDCl3): d = 2.04 (d, JPH = 13.5 Hz, 6 H, 2 ×
CH3).
31P NMR (202 MHz, CDCl3): d = 60.5.
Spectra correspond to published data.16
Methylphosphonic Dichloride (2b)
The methylphosphonic acid (10 mg, 0.10 mmol) was added to a so-
lution of 1-chloro-N,N,2-trimethyl-1-propenylamine (100 mL, 0.76
mmol) in CHCl3 at 50 °C. Within 5 min the reaction was complete
yielding methylphosphonic dichloride (86%).
1H NMR (500 MHz, CDCl3): d = 2.04 (d, JPH = 13.7 Hz, 3 H, CH3).
31P NMR (202 MHz, CDCl3): d = 43.6.
Spectra correspond to published data.17
Phosphonochloridates 3b–10b; General Procedure
We also made an attempt to evaluate chloroenamine as a
solid phase reagent. This seemed to be an attractive ap-
proach mainly due to the easy work-up procedure that
could be foreseen but also because the solid phase reagent
should be recyclable since easy reactivation of the matrix
tethered amide was a likely option. The enamine was built
stepwise on Merrifield resins, starting with isobutyric acid
chloride and an amine linker13 (N,N¢-dimethylethylenedi-
amine) to form an amide which was chlorinated with
phosphorus oxychloride14 or oxalyl chloride15 in good
yields. The reaction of the immobilized chloroenamine
with phosphorus oxyacids, however, did not proceed as
well as in the homogeneous solution reaction since it re-
sulted in the formation of pyrophosphonates in almost
1-Chloro-N,N,2-trimethyl-1-propenylamine (100 mL, 0.76 mmol)
was dissolved in anhyd CHCl3 (1 mL) at 50 °C. The phosphonic
acid (0.3 mmol) was added under Ar atmosphere and allowed to re-
1
act for 2 min. The products were analyzed by 31P NMR and H
NMR spectroscopy. The obtained yields were between 80–95%
(Table 1).
Ethyl Methylphosphonochloridate (3b)
1H NMR (500 MHz, CDCl3): d = 1.41 (t, J = 7.1 Hz, 3 H, CH3), 1.98
(d, JPH = 17.5 Hz, 3 H, CH3), 4.24 (dd, J = 7.2 Hz, JPH = 9.7 Hz, 2
H, CH2).
31P NMR (202 MHz, CDCl3): d = 40.2.
Spectra correspond to published data.18
Neopentyl Methylphosphonochloridate (4b)
quantitative yields. The poor stability of the resin bound 1H NMR (500 MHz, CDCl3): d = 0.98 (s, 9 H, CH3), 2.00 (d, JPH
=
17.5 Hz, 3 H, CH3), 3.77 (dd, J = 7.2 Hz, JPH = 9.4 Hz, 2 H, CH2).
Synthesis 2005, No. 11, 1765–1770 © Thieme Stuttgart · New York

1768
R. Norlin et al.
PAPER
31P NMR (202 MHz, CDCl3): d = 40.7.
Spectra correspond to published data.18
CIMS: m/z (%) = 467 (1.3), 465 (2.0), 323 (1.2), 236 (3.6), 235 (33),
234 (11), 233 (100) [M + H]+, 107 (0.7), 92 (1.9), 91 (20).
Phosphorochloridates 11b, 12b; General Procedure
The 1-chloro-N,N,2-trimethyl-1-propenylamine (100 mL, 0.76
mmol) was dissolved in anhyd tetrachloroethane (1 mL) at 120 °C.
The phosphoric acid (0.3 mmol) was added under Ar and allowed
to react for 5 min.
Menthol Methylphosphonochloridate (5b)
1H NMR (500 MHz, CDCl3): d = 0.84 (d, J = 6.7 Hz, 3 H, CH3), 0.88
(m, 1 H), 0.93, 0.94 (dd, J = 6.5 Hz, 6 H, 2 × CH3, isomers), 1.05
(m, 1 H), 1.23 (m, 1 H), 1.38 (m, 1 H), 1.44–1.50 (m, 1 H), 1.69 (m,
2 H), 1.96, 1.97 (dd, JPH = 17.5 Hz, 3 H, isomers), 2.00–2.12 (m, 1
H), 2.30–2.39 (m, 1 H), 4.38–4.57 (m, 1 H).
Dibutyl Phosphorochloridate (11b)
31P NMR (202 MHz, CDCl3): d = 38.7, 39.5 (isomers).
1H NMR (500 MHz, CDCl3): d = 0.94 (t, J = 7.5 Hz, 6 H, 2 × CH3),
1.42 (m, 4 H, 2 × CH2), 1.72 (m, 4 H, 2 × CH2), 4.18 (m, 4 H, 2 ×
CH2).
EIMS: m/z (%) = 138 (32), 123 (43), 115 (55), 95 (100), 82 (35), 81
(97), 79 (23), 67 (42), 55 (32), 41 (42).
31P NMR (202 MHz, CDCl3): d = 4.77.
Spectra correspond to published data.19
CIMS: m/z (%) = 253 (1.3) [M + H]+, 157 (1.9), 155 (1.8), 140 (11),
139 (100), 138 (4.0), 137 (4.4), 117 (11), 115 (34), 83 (4.0), 81
(1.8).
Diphenyl Phosphorochloridate (12b)
1H NMR (500 MHz, CDCl3): d = 7.17–7.44 (m, 10 H, Ph).
Benzyl Methylphosphonochloridate (6b)
1H NMR (500 MHz, CDCl3): d = 1.95 (d, J = 17.7 Hz, 3 H, CH3),
5.08–5.18 (m, 2 H, CH2), 7.32 (m, 5 H, Bz).
31P NMR (202 MHz, CDCl3): d = –5.15.
Spectra correspond to published data.20
31P NMR (202 MHz, CDCl3): d = 40.8.
EIMS: m/z (%) = 204 (12) [M]+, 107 (100), 98 (13), 91 (67), 90 (24),
89 (17), 79 (22), 77 (10), 65 (20), 51 (10).
Dimethylphosphinic Fluoride (1c)
The reaction procedure was the same as used for the phosphono-
fluoridates (see below) and the reaction was finished within 1 min
with a yield of 98%.
1H NMR (500 MHz, CDCl3): d = 1.68 (dd, JPH = 14.4 Hz, JFH = 8.4
Hz, 6 H, CH3).
19F NMR (471 MHz, CDCl3): d = –65.0 (d, JPF = 991 Hz).
31P NMR (202 MHz, CDCl3): d = 65.1 (d, JFP = 991 Hz).
Spectra correspond to published data.21
CIMS: m/z (%) = 411 (1.2), 409 (1.9), 295 (2.0), 208 (2.9), 207 (33),
206 (9.1), 205 (100) [M + H]+, 204 (1.6), 92 (3.6), 91 (39).
Ethyl Isopropylphosphonochloridate (7b)
1H NMR (500 MHz, CDCl3): d = 1.26–1.35 (m, 6 H, CH3), 1.40 (m,
3 H, CH3), 2.29 (m, 1 H, CH), 4.33 (m, 2 H, CH2).
31P NMR (202 MHz, CDCl3): d = 51.5.
Spectra correspond to published data.18
Methylphosphonic Difluoride (2c)
Neopentyl Isopropylphosphonochloridate (8b)
1H NMR (500 MHz, CDCl3): d = 0.96 (s, 9 H, CH3), 1.26 (dd, J =
7.4 Hz, JPH = 19.7 Hz, 6 H, CH3), 2.10–2.21 (m, 1 H, CH), 3.77–
3.87 (m, 2 H, CH2).
The methylphosphonic acid (5 mg, 0.05 mmol) was added to a so-
lution of 1-fluoro-N,N,2-trimethyl-1-propenylamine (50 mL, 0.43
mmol) in tetrachlorethane (0.5 mL) at 120 °C. The reaction was
complete within 5 min and the yield was quantitative.
1H NMR (500 MHz, CDCl3): d = 1.90 (dt, JPH = 19.2 Hz, JFH = 6.0
Hz, 3 H).
19F NMR (471 MHz, CDCl3): d = –58.8 (d, JPF = 1110 Hz).
31P NMR (202 MHz, CDCl3): d = 24.4 (t, JFP = 1110 Hz).
Spectra correspond to published data.22
31P NMR (202 MHz, CDCl3): d = 51.4.
EIMS: m/z (%) = 158 (29), 156 (89), 143 (86), 114 (79), 71 (36), 57
(39), 55 (75), 43 (100), 41 (73), 39 (29).
CIMS: m/z (%) = 427 (1.9), 425 (3.0), 216 (2.8), 215 (32), 214 (8.7),
213 (100) [M + H]+, 183 (2.5), 145 (28), 144 (2.9), 143 (85).
Menthol Isopropylphosphonochloridate (9b)
1H NMR (500 MHz, CDCl3): d = 0.83 (q, J = 2.88, 7.0 Hz, 3 H),
0.87–0.90 (m, 1 H), 0.92, 0.93 (dd, J = 6.5 Hz, 6 H, 2 × CH3, iso-
mers), 1.05 (m, 1 H), 1.20 (m, 1 H), 1.30–1.33 (m, 6 H), 1.37–1.41
(m, 1 H), 1.45–1.50 (m, 1 H), 1.69 (m, 2 H), 2.06–2.12 (m, 1 H),
2.22–2.31 (m, 1 H), 2.33–2.37 (m, 1 H), 4.38–4.57 (m, 1 H).
Phosphonofluoridates 3c–10c; General Procedure
1-Fluoro-N,N,2-trimethyl-1-propenylamine (100 mL, 0.85 mmol)
was dissolved in anhyd tetrachloroethane (1 mL) at 120 °C. The
phosphonic acid (0.3 mmol) was added under Ar and allowed to re-
act for 5 min. The products were analyzed by 31P NMR, 19F NMR
and 1H NMR spectroscopy. The obtained yields were between 75–
98% (Table 1).
31P NMR (202 MHz, CDCl3): d = 49.7, 50.7 (isomers).
EIMS: m/z (%) = 145 (32), 143 (100), 138 (31), 123 (23), 95 (67),
81 (44), 67 (20), 55 (24), 43 (32), 41 (34).
Ethyl Methylphosphonofluoridate (3c)
1H NMR (500 MHz, CDCl3): d = 1.64 (dd, JPH = 18.5 Hz, JFH = 5.8
Hz, 3 H, CH3), 1.38 (t, J = 7.2 Hz, 3 H, CH3), 4.24 (m, 2 H, CH2).
CIMS: m/z (%) = 281 (1.1) [M + H]+, 185 (1.6), 183 (1.5), 181 (1.4),
145 (32), 144 (3.5), 143 (100), 140 (1.5), 139 (14), 138 (3.6), 137
(4.1).
19F NMR (471 MHz, CDCl3): d = –58.9 (d, JPF = 1048 Hz).
31P NMR (202 MHz, CDCl3): d = 29.8 (d, JFP = 1048 Hz).
Spectra correspond to published data.23
Benzyl Isopropylphosphonochloridate (10b)
1H NMR (500 MHz, CDCl3): d = 1.27–1.35 (m, 6 H, CH3), 2.28–
2.40 (m, 1 H, CH), 5.15 (dd, J = 8.9 Hz, JPH = 11.5 Hz, 1 H, CH2),
5.28 (dd, J = 8.9 Hz, JPH = 11.3 Hz, 1 H, CH2), 7.39 (m, 5 H, Bz).
Neopentyl Methylphosphonofluoridate (4c)
1H NMR (500 MHz, CDCl3): d = 0.95 (s, 9 H, CH3), 1.66 (dd, JFH
=
31P NMR (202 MHz, CDCl3): d = 52.2.
EIMS: m/z (%) = 232 (14) [M]+, 126 (32), 107 (100), 91 (99), 90
5.5 Hz, JPH = 18.7 Hz, 3 H, CH3), 3.80 (dd, J = 6.0, 9.6 Hz, 1 H,
CH2), 3.86 (ddd, J = 1.4, 6.7, 9.6 Hz, 1 H, CH2).
(13), 79 (14), 65 (26), 43 (34), 41 (12), 39 (13).
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Halides of Phosphorous Oxyacids Prepared with a-Haloenamines
1769
19F NMR (471 MHz, CDCl3): d = –59.3 (d, JPF = 1048 Hz).
31P NMR (202 MHz, CDCl3): d = 29.7 (d, JFP = 1048 Hz).
Spectra correspond to published data.23
19F NMR (471 MHz, CDCl3): d = –69.3 (d, JPF = 1088 Hz), –72.3
(d, JPF = 1086 Hz, isomers).
31P NMR (202 MHz, CDCl3): d = 34.1 (d, JFP = 1088 Hz), 33.6 (d,
JFP = 1086 Hz, isomers).
Menthol Methylphosphonofluoridate (5c)
EIMS: m/z (%) = 138 (42), 127 (93), 123 (46), 95 (100), 82 (33), 81
(86), 67 (35), 55 (29), 43 (40), 41 (44).
CIMS: m/z (%) = 265 (1.1) [M + H]+, 167 (1.7), 165 (1.6), 140 (5.7),
139 (51), 138 (4.0), 137 (4.4), 128 (3.4), 127 (100), 83 (2.6), 81
(1.2).
1H NMR (500 MHz, CDCl3): d = 0.81 (d, J = 7.0 Hz, 3 H, CH3),
0.85–0.87 (m, 1 H), 0.92 (d, J = 7.0 Hz, 6 H, 2 × CH3), 1.05 (m, 1
H), 1.16–1.24 (m, 1 H), 1.34–1.38 (m, 1 H), 1.44–1.50 (m, 1 H),
1.59 (dd, JFH = 3.4 Hz, JPH = 17.3 Hz, 3 H, CH3), 1.63–1.68 (m, 2
H), 2.20–2.24 (m, 1 H), 2.29–2.38 (m, 1 H), 4.34–4.46 (m, 1 H).
19F NMR (471 MHz, CDCl3): d = –53.6 (d, JPF = 1049 Hz), –57.2
(d, JPF = 1047 Hz, isomers).
31P NMR (202 MHz, CDCl3): d = 29.1 (d, JFP = 1049 Hz), 28.4 (d,
JFP = 1048 Hz, isomers).
Benzyl Isopropylphosphonofluoridate (10c)
1H NMR (500 MHz, CDCl3): d = 1.24 (dd, J = 7.2 Hz, JPH = 19.9
Hz, 6 H, CH3), 2.08–2.19 (m, 1 H, CH), 5.14–5.25 (m, 2 H, CH2),
7.39 (s, 5 H, Bz).
19F NMR (471 MHz, CDCl3): d = –73.3 (d, JPF = 1094 Hz).
31P NMR (202 MHz, CDCl3): d = 35.4 (d, JFP = 1094 Hz).
EIMS: m/z (%) = 138 (27), 123 (43), 99 (77), 96 (21), 95 (94), 82
(33), 81 (100), 67 (41), 55 (28), 41 (37).
CIMS: m/z (%) = 237 (0.6) [M + H]+, 141 (1.3), 140 (11), 139 (100),
EIMS: m/z (%) = 216 (24) [M]+, 108 (11), 107 (100), 91 (86), 90
138 (2.6), 137 (3.8), 99 (13), 95 (0.6), 83 (3.6), 81 (1.3).
(38), 89 (15), 79 (16), 65 (22), 43 (17), 39 (13).
CIMS: m/z (%) = 433 (2.5), 307 (1.5), 219 (1.0), 218 (11), 217 (100)
Benzyl Methylphosphonofluoridate (6c)
[M + H]+, 216 (2.3), 127 (1.1), 107 (0.7), 92 (2.9), 91 (32).
1H NMR (500 MHz, CDCl3): d = 1.59 (dd, JFH = 5.8 Hz, JPH = 18.7
Hz, 3 H, CH3), 4.87–4.93 (m, 1 H, CH2), 4.97–5.02 (m, 1 H, CH2),
7.33 (s, 5 H, Bz).
Phosphorofluoridates 11c, 12c; General Procedure
The procedure was the same as used for phosphonofluoridates (see
above).
19F NMR (471 MHz, CDCl3): d = –57.9 (d, JPF = 1054 Hz).
31P NMR (202 MHz, CDCl3): d = 30.3 (d, JFP = 1054 Hz).
EIMS: m/z (%) = 188 (49) [M]+, 107 (92), 91 (67), 90 (100), 89 (44),
Dibutyl Phosphorofluoridate (11c)
1H NMR (500 MHz, CDCl3): d = 0.94 (t, J = 7.2 Hz, 6 H), 1.39–1.45
(m, 4 H), 1.67–1.72 (m, 4 H), 4.14–4.20 (m, 4 H).
79 (20), 77 (14), 65 (25), 51 (15), 39 (16).
19F NMR (471 MHz, CDCl3): d = –81.4 (d, JPF = 978 Hz).
31P NMR (202 MHz, CDCl3): d = –8.8 (d, JFP = 978 Hz).
Spectra correspond to published data.24
CIMS: m/z (%) = 377 (2.2), 279 (2.2), 190 (8.8), 189 (100) [M +
H]+, 188 (2.8), 181 (1.5), 107 (0.7), 99 (1.9), 92 (6.2), 91 (69).
Ethyl Isopropylphosphonofluoridate (7c)
1H NMR (500 MHz, CDCl3): d = 1.24 (dd, J = 6.7 Hz, JPH = 20.2
Hz, 6 H, CH3), 1.38 (t, J = 7.2 Hz, 3 H, CH3), 2.05–2.17 (m, 1 H,
CH), 4.19–4.27 (m, 2 H, CH2).
Diphenyl Phosphorofluoridate (12c)
1H NMR (500 MHz, CDCl3): d = 7.17–7.42 (m, 10 H).
19F NMR (471 MHz, CDCl3): d = –73.9 (d, JPF = 1088 Hz).
31P NMR (202 MHz, CDCl3): d = 35.0 (d, JFP = 1088 Hz).
19F NMR (471 MHz, CDCl3): d = –77.4 (d, JPF = 1003 Hz).
31P NMR (202 MHz, CDCl3): d = –21.4 (d, JFP = 1003 Hz).
Spectra correspond to published data.20
EIMS: m/z (%) = 139 (14), 127 (100), 126 (22), 111 (48), 85 (21),
84 (60), 43 (64), 42 (14), 41 (31), 29 (15).
1-Fluoro-N,N,2-trimethyl-1-propenylamine (13)
CIMS: m/z (%) = 311 (0.1), 310 (0.5), 309 (4.0), 195 (0.8), 193
CsF (20 g, 132 mmol) was dried at 350 °C for 12 h and then trans-
ferred to a round bottom flask. Anhydrous 1,3-dichlorobenzene (10
mL) was added and the slurry was stirred using a magnetic stirrer.
1-Chloro-N,N,2-trimethyl-1-propenylamine (3 mL, 22.7 mmol)
was added and the reaction was heated to 110 °C for 36 h under Ar
atmosphere. A distillation head and Liebig condenser were attached
and the product was distilled (bp 120–125°C/740 torr) to produce
the amine 13 (2.1 g; 79%).
(0.2), 167 (0.2), 157 (0.5), 156 (5.7), 155 (100) [M + H]+, 127 (0.8).
Neopentyl Isopropylphosphonofluoridate (8c)
1H NMR (500 MHz, CDCl3): d = 0.96 (s, 9 H, CH3), 1.26 (dd, JPH
=
20.0 Hz, J = 7.5 Hz, 6 H, CH3), 2.11–2.21 (m, 1 H, CH), 3.77–3.81
(m, 1 H, CH2), 3.83–3.88 (m, 1 H, CH2)
19F NMR (471 MHz, CDCl3): d = –75.0 (d, JPF = 1088 Hz).
31P NMR (202 MHz, CDCl3): d = 34.4 (d, JFP = 1088 Hz).
1H NMR (500 MHz, CDCl3): d = 1.60 (q, J = 16.5 Hz, J = 3 Hz, 6
H, CH3), 2.53 (d, J = 1.5 Hz, 6 H, CH3).
EIMS: m/z (%) = 140 (100), 127 (65), 125 (49), 112 (44), 98 (38),
13C NMR (126 MHz, CDCl3): d = 17.1 (2 × C, CH3), 41.2 (2 × C,
NCH3), 99.9 (d, J = 36.5 Hz, 1 C, CH), 155.4 (d, JFC = 277 Hz, 1 C,
CF)
19F NMR (471 MHz, CDCl3): d = –114.
57 (31), 55 (59), 43 (57), 41 (53), 39 (22).
CIMS: m/z (%) = 394 (1.0), 393 (6.0), 323 (1.3), 235 (0.6), 198
(4.9), 197 (56) [M + H]+, 167 (2.2), 140 (0.7), 128 (3.5), 127 (100).
Menthol Isopropylphosphonofluoridate (9c)
1H NMR (500 MHz, CDCl3): d = 0.82 (q, J = 6.7, 5.3 Hz, 3 H, CH3),
0.84–0.89 (m, 1 H), 0.92 (d, J = 6.7 Hz, 6 H, 2 × CH3), 0.97–1.05
(m, 1 H), 1.14–1.19 (m, 1 H), 1.24 (dd, J = 6.7 Hz, JPH = 20.6 Hz, 6
H, CH3), 1.32–1.38 (m, 1 H), 1.42–1.50 (m, 1 H), 1.65–1.69 (m, 2
H), 2.02–2.13 (m, 1 H), 2.14–2.22 (m, 1 H), 2.35–2.40 (m, 1 H),
4.34–4.44 (m, 1 H).
Acknowledgment
The authors wish to thank Sten-Åke Fredriksson for recording EI-,
and CIMS data.
Synthesis 2005, No. 11, 1765–1770 © Thieme Stuttgart · New York

1770
R. Norlin et al.
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