Selective Substitution of POCl 3 with Organometallic Reagents: Synthesis of Phosphinates and Phosphonates

Article abstract of DOI:10.1055/s-0037-1609435

The selectivity of the substitution reaction of phosphoryl chloride with organometallic reagents was investigated using NMR spectroscopy. This led to the discovery that the selectivity of the substitution reaction can be tuned by choosing a proper organometallic reagent. A phosphinate could be obtained by using a Grignard reagent whereas an organozinc reagent provided a phosphonate. Based on these results, one-pot synthetic methods for the preparation of phosphinates and phosphonates using commercially available starting materials were developed. Both methods allow the synthesis of a broad range of either phosphinate or phosphonate derivatives in a straightforward and general procedure. Moreover, using these one-pot procedures, mixed systems substituted with different alkyl/aryl groups can be prepared.

Full text of DOI:10.1055/s-0037-1609435

SYNTHESIS
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Georg Thieme Verlag Stuttgart · New York
2018, 50, A–H
paper
A
en
B. Verbelen et al.
Paper
Synthesis
Selective Substitution of POCl3 with Organometallic Reagents:
Synthesis of Phosphinates and Phosphonates
Bram Verbelen
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2
1-
8
6
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3-
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one-pot
Mg
one-pot
Zn
O
O
P
O
P
Wim Dehaen
0
0
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2
9-
5
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R1
P
OR2
Cl
Cl
R1
OR2
Koen Binnemans*
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4-
7
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8
3-
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R1
OR2
Cl
phosphinate
6 examples
1–3 g scale
phosphonate
6 examples
0.5–2 g scale
Molecular Design and Synthesis, Department of Chemistry,
KU Leuven, Celestijnenlaan 200F, Box 2404, 3001 Leuven,
Belgium
koen.binnemans@kuleuven.be
Received: 07.02.2018
Accepted after revision: 27.02.2018
Published online: 05.04.2018
typically as prodrugs for their corresponding acid deriva-
tives.7 Noteworthy examples are nucleoside phosphonates
applied in the treatment of various DNA virus and retro-
virus infections, such as hepatitis B and HIV.8
DOI: 10.1055/s-0037-1609435; Art ID: ss-2018-z0081-op
License terms:
However, the utility of organophosphinates 1 is limited
by their tedious multistep synthesis. The corresponding
phosphinic acids 3 are the key intermediates in this synthe-
sis and they form, after activation to phosphinic halides, the
desired phosphinates 1 via a nucleophilic substitution reac-
tion (Scheme 1, path A).9 Of course, first the organophos-
phinic acids 3 need to be prepared using, for example, a
hydrophosphonation reaction of alkenes with hypophos-
phorous acid 4,10 a reaction between dialkyl hydrogen
phosphites 5 and organometallic reagents followed by oxi-
dation,10 etc.11,12 A generic strategy towards phosphinates 1
is not available yet.10,13 The used synthetic pathway is
therefore dependent on the structure of the desired
phosphinate 1.
Abstract The selectivity of the substitution reaction of phosphoryl
chloride with organometallic reagents was investigated using NMR
spectroscopy. This led to the discovery that the selectivity of the substi-
tution reaction can be tuned by choosing a proper organometallic re-
agent. A phosphinate could be obtained by using a Grignard reagent
whereas an organozinc reagent provided a phosphonate. Based on
these results, one-pot synthetic methods for the preparation of
phosphinates and phosphonates using commercially available starting
materials were developed. Both methods allow the synthesis of a broad
range of either phosphinate or phosphonate derivatives in a straightfor-
ward and general procedure. Moreover, using these one-pot proce-
dures, mixed systems substituted with different alkyl/aryl groups can
be prepared.
Key words selectivity, substitution, phosphoryl chloride, phosphi-
nate, phosphonate, Grignard reagent, organozinc reagent
A more generic strategy is known for organophospho-
nates 2. Phosphorus trichloride (6) can be substituted with
an excess of alcohol in the presence of base and the result-
ing phosphite ester 7 can be subjected to an Michaelis–
Arbuzov reaction with a haloalkane to form a phosphonate
2 (Scheme 1, path B).1,10,13 However, the latter reaction re-
quires high temperatures and only primary haloalkanes
react readily. Under certain conditions, secondary halo-
alkanes might also react, but tertiary haloalkanes and
haloarenes are unreactive in the Michaelis–Arbuzov reac-
tion.14 Moreover, when the alkyl group of the alcohol and
the haloalkane are different, a mixture of phosphonates 2
might be formed. Besides this strategy, other less general
synthetic pathways towards phosphonates 2 have also been
described.1b,11,15
Organophosphinates 1 and organophosphonates 2, the
ester derivatives of organophosphinic 3 and organophos-
phonic acids, can be seen as intermediate compounds be-
tween the corresponding phosphates and phosphine ox-
ides. Hence, the chemical, physical, and biological proper-
ties of phosphinates 1 and phosphonates 2 are in between
these two extremes.1 The synthesis of phosphinate 1 and
phosphonate 2 derivatives is therefore an attractive ap-
proach to fine-tune the characteristics of organophospho-
rus(V) compounds. The attractiveness of these two classes
of molecules is illustrated by their many applications. For
example, they are used as halogen-free flame retardants in
plastics,2 as extractants for liquid-liquid extraction in hydro-
metallurgy,3 and solvometallurgy,4 as grafting agents to
modify metal oxide surfaces,5 and as reagents for olefina-
tion reactions.6 Moreover, phosphinates 1 and phospho-
nates 2 are important in the treatment of several diseases,
A more straightforward and general strategy to synthe-
size both phosphinates 1 and phosphonates 2 could be
envisioned as the reaction between phosphoryl chloride (8)
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

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B. Verbelen et al.
Paper
Synthesis
the synthesis of phosphinates 1 and phosphonates 2. Based
on the results, practical one-pot syntheses of phosphinates
1 and phosphonates 2 using commercially available starting
materials were developed (Scheme 1, path C).
Previous work
A)
O
P
H
4
H
OH
O
P
O
The first step of this work was to study the selectivity of
the substitution reaction of phosphoryl chloride (8) with
one or two equivalents of Grignard reagent. In order to limit
over-substitution, the Grignard reagent was slowly added
to an anhydrous diethyl ether solution of phosphoryl chlo-
ride (8) while the solution was being cooled using an ice-
salt mixture. Diethyl ether was chosen as the reaction sol-
vent because all the Grignard reagents used in this study
are commercially available as diethyl ether solutions. After
addition of the Grignard reagent, the reaction was stirred at
room temperature to achieve complete conversion. Samples
were then taken and analyzed by 31P NMR spectroscopy to
estimate the relative amounts of the formed products. Pre-
liminary experiments with phenylmagnesium bromide
showed that the formed phenylphosphonic dichloride and
diphenylphosphinic chloride were too poorly soluble in di-
ethyl ether16a to allow analysis of the reaction mixture by
31P NMR spectroscopy. Because octylphosphonic dichloride
and dioctylphosphinic chloride are more soluble, the selec-
tivity of the substitution reaction was determined by using
octylmagnesium bromide as the Grignard reagent.
Reacting one equivalent of octylmagnesium bromide
with phosphoryl chloride (8) resulted in less than 10% of
the desired octylphosphonic dichloride compound 9a (Ta-
ble 1, entry 1). Instead, about half of the reaction mixture
was doubly reacted dioctylphosphinic chloride (10a) and
the other half unreacted phosphoryl chloride (8). Thus, the
added octylmagnesium bromide reacted twice with phos-
phoryl chloride (8), which is in agreement with the report-
ed tendency of Grignard reagents to completely substitute
phosphoryl chloride (8).1a,13 This lack of selectivity for
monofunctionalization might be explained by considering
the magnesium salt that is formed as a side product during
the reaction. This Lewis acid will probably coordinate
stronger to the more electron-rich octylphosphonic dichlo-
ride (9a) than to phosphoryl chloride (8), making the re-
sulting octylphosphonic dichloride complex more electro-
philic and hence more reactive toward the Grignard re-
agent.
R1
OH
R1
P
OR2
R1
R1
OH
P
3
1
RO
OR
5
Cl
P
OR2
P
O
B)
Cl
R1
P
OR2
Cl
R2O
OR2
OR2
6
7
2
Present work
C)
O
O
P
O
P
OR2
one-pot
one-pot
R1
P
OR2
Cl
Cl
R1
OR2
R1
Cl
8
1
2
Scheme 1 Brief summary of the synthetic pathways towards organo-
phosphinates 1 and organophosphonates 2
and, respectively, two or one equivalents of Grignard re-
agent, followed by quenching with an excess of alcohol
(Scheme 1, path C). This one-pot procedure would be short-
er than the conventional synthetic strategies, would use
milder reaction conditions (i.e., heating is not required) and
would allow different substituents on the phosphorus (R1)
and oxygen (R2) atoms. However, this one-pot protocol is
currently not used for the synthesis of either phosphinates
1 or phosphonates 2. A poorly selective substitution of
phosphoryl chloride (8) with Grignard reagents is often cit-
ed as the reason why this one-pot procedure is unsuitable
for the synthesis of phosphinates 1 and phosphonates 2.1a,13
According to the literature, Grignard reagents have a ten-
dency to completely substitute phosphoryl chloride (8), but
a detailed study of the extent of the side reactions has not
been reported yet.13 It should also be noted that many
examples that resulted in over-substitution used an un-
favorable addition order of the reagents, namely phosphor-
yl chloride (8) was added to the Grignard reagent. Adding
the Grignard reagent to phosphoryl chloride (8) can be
expected to give better yields.16 Moreover, reported exam-
ples of the reaction between phosphoryl chloride (8) and
organometallic reagents were typically limited to aryl
Grignard reagents,16a whereas alkyl groups and other or-
ganometallic reagents have been much less studied. Fur-
thermore, most of these reports involved quenching the re-
action with water, forming a phosphinic or phosphonic
acid. Preparing esters by quenching the reaction with dif-
ferent alcohols is less common.
In contrast to using one equivalent, reacting two equiva-
lents of octylmagnesium bromide with phosphoryl chloride
(8) did result in a selective reaction (Table 1, entry 4). Al-
most 75% of the reaction mixture consisted of the desired
dioctylphosphinic chloride (10a), whereas only approxi-
mately 15% octylphosphonic dichloride (9a) and a trace of
trioctylphosphine oxide were formed. This shows that, con-
trary to what is typically assumed in the literature, selec-
tive disubstitution of phosphoryl chloride (8) with two
equivalents of a Grignard reagent is possible. This selectivi-
ty might be explained by considering the steric hindrance
Given the current poor understanding of the extent of
the selectivity for the substitution reaction of phosphoryl
chloride (8) with organometallic reagents, we set out to in-
vestigate this selectivity using NMR spectroscopy and to ex-
amine the possibility of using this substitution reaction in
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

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B. Verbelen et al.
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Synthesis
Table 1 Percentage of Phosphorus Compounds in the Reaction Mix-
ture after P(O)Cl3 has Reacted with 1 or 2 Equiv of an Octylorgano-
metallic Reagent
sized in a similar yield by starting from the correspondingly
branched Grignard reagent and alcohol. Besides alkyl
Grignard reagents, phenylmagnesium bromide also allowed
selective disubstitution of phosphoryl chloride (8). Howev-
er, phenol was not reactive enough to substitute the result-
ing diphenylphosphinic chloride intermediate. Nonetheless,
1-octanol could react with diphenylphosphinic chloride
and octyl diphenylphosphinate (1d) was isolated in a
slightly lower yield than the other synthesized phosphi-
nates 1.
Entry RMa
Composition of reaction mixture (%)b
P(O)Cl3
RP(O)Cl2
R2P(O)Cl
43
R3P(O)
1
1
2
3
4
RMgX (1 equiv)
43
43
22
9
c
c
R2Cd (0.5 equiv)
R2Zn (0.5 equiv)
RMgX (2 equiv)
48
73
15
–
–
c
c
–
–
c
–
73
2
The last example illustrates another advantage of this
one-pot procedure, namely that the substituents on the
phosphorus (R1) and oxygen (R2) atoms of the resulting
phosphinate 1 do not need to be the same. Mixed phosphi-
nates 1d–f can be easily made using the same procedure
and in similar yields. For example, reaction of phosphoryl
chloride (8) with two equivalents of octylmagnesium bro-
mide followed by quenching with an excess of 2-ethylhexa-
nol resulted in 2-ethylhexyl dioctylphosphinate (1e) in a
good yield of 58%. In a similar way, a phosphinic acid could
be synthesized if the dioctylphosphinic chloride intermedi-
ate was quenched with water. After extraction and recrys-
tallization, dioctylphosphinic acid (1f) was isolated in an
acceptable yield.
This one-pot procedure is, compared to the different
traditional multistep synthesis routes of phosphinates 1,
much more straightforward and general. Moreover, the
overall yield of this process is, due to its shorter synthetic
pathway, as good as or even better than those obtained via
the traditional synthesis routes (Scheme 1, path A).9,10,11,13
Given the success of disubstitution of phosphoryl
chloride (8), selective monofunctionalization was further
investigated using organometallic reagents other than
Grignard reagents. Similar to phosphoryl chloride (8), reac-
tion of phosphorus trichloride (6) with Grignard reagents is
known to result in over-substitution.1a,17 However, is has
been reported that reaction of phosphorus trichloride (6)
with milder alkylating reagents, such as organomercury,18
organolead19 and organocadmium20 reagents, did allow
selective monoalkylation. Therefore, it was tested whether
an organocadmium reagent could result in a similar selec-
tive monofunctionalization reaction with phosphoryl chlo-
ride (8). Organomercury and organolead compounds were
not investigated due to their very high toxicity.21 It should
be mentioned that also organocadmium compounds are
toxic; however, they are less toxic than organomercury
compounds and they are more commonly used as reagents
in organic synthesis than organolead compounds.22
a R = n-C8H17
.
b Percentage of phosphorus compounds in the reaction mixture as estimat-
ed by 31P NMR analysis.
c Compound was not detected.
of the reaction between dioctylphosphinic chloride (10a)
and the Grignard reagent. Hence, this side reaction with di-
octylphosphinic chloride (10a) will be less favorable than
the less sterically hindered reaction with octylphosphonic
dichloride (9a).
Given that the above-mentioned reaction mixture con-
sisted mostly of dioctylphosphinic chloride, it should be
possible to synthesize octyl dioctylphosphinate (1a) by
quenching the reaction with an excess of 1-octanol. After
addition of 1-octanol at a temperature below 0 °C, the reac-
tion was stirred at room temperature until 31P NMR analy-
sis showed complete consumption of the dioctylphosphinic
chloride intermediate. It was found that pyridine needed to
be added together with 1-octanol. In this way, the formed
side product HCl could be neutralized and complete con-
version could be achieved. This resulted in a reaction mix-
ture that consisted mostly of the desired octyl dioctyl-
phosphinate (1a) together with a small amount of dioctyl
octylphosphonate (2a). After extractive workup and purifi-
cation by column chromatography, octyl dioctylphosphi-
nate (1a) was isolated in a good yield of 63% (Scheme 2).
R1MgX
(2 equiv)
O
O
O
P
R2OH
R1
P
R1
Cl
R1
P
R1
OR2
Cl
Cl
Et2O
pyridine
Cl
8
10a–f
1a–f
1a, R1 = R2 = octyl (63%)
1b, R1 = R2 = dodecyl (55%)
1c, R1 = R2 = 2-ethylhexyl (52%)
1d, R1 = phenyl, R2 = octyl (44%)
1e, R1 = octyl, R2 = 2-ethylhexyl (58%)
1f, R1 = octyl, R2 = H (52%)
Scheme 2 One-pot synthesis of phosphinates 1 using a selective
disubstitution of P(O)Cl3 with 2 equiv of Grignard reagents
Similar results could be obtained with other alkyl
groups (Scheme 2). Reaction of phosphoryl chloride (8)
with two equivalents of dodecylmagnesium bromide, fol-
lowed by quenching with an excess of 1-dodecanol provid-
ed dodecyl didodecylphosphinate (1b) in an isolated yield
of 55%. Furthermore, the more sterically hindered 2-ethyl-
hexyl bis(2-ethylhexyl)phosphinate (1c) could be synthe-
Dioctylcadmium was synthesized in situ by the reaction
of octylmagnesium bromide with anhydrous CdCl2 in dieth-
yl ether at room temperature. After addition of one equiva-
lent (relative to the initial amount of octylmagnesium bro-
mide) of phosphoryl chloride (8) at a temperature below
0 °C, the reaction mixture was stirred at room temperature.
Unfortunately, no reaction was observed at this tempera-
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

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B. Verbelen et al.
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Synthesis
ture. Nevertheless, a slow reaction did occur when the reac-
tion mixture was heated at reflux. Over-substitution to di-
octylphosphinic chloride (10a) was not detected and the
major product was the desired octylphosphonic dichloride
(9a) (Table 1, entry 2). Hence, with this less strongly
alkylating organocadmium reagent, selective monofunc-
tionalization of phosphoryl chloride (8) was indeed possi-
ble. After 45 hours, almost half of the reaction mixture con-
sisted of the monoalkylated product, the rest was mostly
unreacted phosphoryl chloride (8).
R12Zn
(0.5 equiv)
O
P
O
P
OR2
O
P
R2OH
R1
Cl
R1
OR2
Cl
Cl
Et2O
pyridine
Cl
Cl
8
9a–f
2a–f
2a, R1 = R2 = octyl (46%)
2b, R1 = R2 = dodecyl (36%)
2c, R1 = R2 = 2-ethylhexyl (42%)
2d, R1 = phenyl, R2 = octyl (14%)
2e, R1 = octyl, R2 = 2-ethylhexyl (43%)
2f, R1 = octyl, R2 = H (30%)
Scheme 3 One-pot synthesis of phosphonates 2 using a selective mo-
nosubstitution of P(O)Cl3 with 0.5 equiv of organozinc reagents (pyri-
dine was not added in the case of phosphonic acid 2f)
As dioctylcadmium was not reactive enough to allow
complete conversion, even after 45 hours of reflux, di-
octylzinc was used as a more reactive and less toxic alterna-
tive. Dioctylzinc was synthesized and used in a similar
manner as dioctylcadmium. However, due to its higher re-
activity, dioctylzinc did react with phosphoryl chloride (8)
at room temperature. After 20 hours, almost 75% of the re-
action mixture consisted of the desired octylphosphonic di-
chloride (9a) (Table 1, entry 3). Dioctylzinc reacted, just like
dioctylcadmium, selectively with phosphoryl chloride (8)
and over-substitution to dioctylphosphinic chloride (10a)
was not detected. The amount of monooctyl product in the
reaction mixture after reaction with 0.5 equivalent of di-
octylzinc (Table 1, entry 3) was similar to the amount of di-
octyl product after reaction with 2 equivalents of Grignard
reagent (Table 1, entry 4). Therefore, it is possible to tune
the selectivity of the substitution reaction of phosphoryl
chloride (8) by choosing a proper organometallic reagent.
Selective monoalkylation of phosphoryl chloride (8) to
octylphosphonic dichloride was used next to develop a
one-pot procedure for the synthesis of the corresponding
phosphonate 2a. Hence, the reaction of dioctylzinc with
phosphoryl chloride (8) was quenched with an excess of 1-
octanol in the presence of pyridine. The reaction mixture
was cooled below 0 °C during the addition of these two re-
agents and was afterwards stirred at room temperature un-
til 31P NMR analysis showed complete consumption of the
octylphosphonic dichloride intermediate. The resulting
mixture consisted mostly of dioctyl octylphosphonate (2a)
together with a smaller amount of trioctyl phosphate. This
trioctyl phosphate was formed from the reaction between
1-octanol and the remaining phosphoryl chloride (8). Un-
fortunately, the desired dioctyl octylphosphonate (2a) was
found to be less stable than the corresponding phosphinate
1a. Therefore, more product was lost during purification
and dioctyl octylphosphonate (2a) was isolated in a lower
yield of 46% (Scheme 3).
hexyl (in compounds 2c and 2e) could be synthesized in
moderate yields. In contrast, reaction of phosphoryl chlo-
ride (8) with diphenylzinc followed by quenching with an
excess of 1-octanol gave the corresponding dioctyl phenyl-
phosphonate (2d) in a low yield. The major product was ac-
tually trioctyl phosphate and a significant amount of octyl
diphenylphosphinate (1d) was also present, indicating that
0.5 equivalent of diphenylzinc did not react selectively with
phosphoryl chloride (8).
Mixed phosphonates, with different substituents on the
phosphorus (R1) and oxygen (R2) atoms, can be easily pre-
pared using this one-pot procedure. For example, bis(2-ethyl-
hexyl) octylphosphonate (2e) was obtained in a similar
yield as its trioctyl derivative 2a by reacting dioctylzinc
with phosphoryl chloride (8) followed by quenching with
an excess of 2-ethylhexanol. Moreover, octylphosphonic
acid (2f) can be synthesized by quenching the reaction of
dioctylzinc with water. Anhydride formation limited the
yield of the desired acid 2f but this can be reduced by not
adding pyridine to the reaction mixture. In this way, octyl-
phosphonic acid (2f) was isolated in a moderate yield.
The yields of the one-pot synthesis of phosphonates 2
are in general lower than those obtained for the traditional
synthesis of phosphonates 2 based on the Michaelis–Arbuzov
reaction (Scheme 1, path B).1,10,13 Nevertheless, this new
procedure is a viable alternative for those cases where the
Michaelis–Arbuzov reaction does not work.14 Moreover,
this one-pot synthesis requires only one purification step,
compared to the two purification steps required in the tra-
ditional strategy, uses milder reaction conditions than the
Michaelis–Arbuzov reaction and is well suited for the syn-
thesis of mixed phosphonates.
In conclusion, the selectivity of the substitution reac-
tion of phosphoryl chloride (8) with organometallic re-
agents was investigated using NMR spectroscopy. It was
found that 2 equivalents of octylmagnesium bromide react-
ed selectively to dioctylphosphinic chloride and that 0.5
equivalent of dioctylzinc reacted selectively to octylphos-
phonic dichloride. Hence, it is possible to tune the selectivi-
ty of the substitution reaction of phosphoryl chloride (8) by
choosing a proper organometallic reagent. These results
were used to develop one-pot synthetic methods for the
preparation of phosphinates 1 and phosphonates 2 using
The scope of the one-pot synthesis of phosphonates 2
(Scheme 3) is the same as the scope of the one-pot synthe-
sis of phosphinates 1 (Scheme 2). Unfortunately, all the syn-
thesized phosphonates 2 were less stable than their
phosphinate analogues 1 and were isolated in a lower yield.
Nonetheless, phosphonates 2 with other alkyl groups, such
as dodecyl (in compound 2b) and the branched 2-ethyl-
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

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B. Verbelen et al.
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Synthesis
commercially available Grignard reagents and alcohols. In
this way, phosphinates 1 were synthesized in good yields
and phosphonates 2, due to their lower stability, in moder-
ate yields. Both procedures allow the synthesis of com-
pounds with different substituents, of mixed systems and
of their phosphinic and phosphonic acid derivatives. Com-
pared to the traditional strategies to synthesize phosphi-
nates 1 and phosphonates 2, these one-pot procedures are
shorter, more straightforward and more general.
Prepared according to the general phosphinate synthesis procedure
using anhyd Et2O (20 mL), octylmagnesium bromide (10 mL, 20
mmol, 2 equiv), and 1-octanol (3.2 mL, 20 mmol, 2 equiv). The reac-
tion with the Grignard reagent was stirred at r.t. for 5 h and the reac-
tion with the alcohol was stirred at r.t. for 21 h. After extractive work-
up, the excess of 1-octanol was removed using a short-path vacuum
distillation apparatus at 250 °C. The resulting crude product was pu-
rified by column chromatography (silica gel; CH2Cl2/EtOAc; 8:2 v/v),
providing the pure compound as a slightly yellowish liquid; yield:
2.52 g (63%).
IR (ATR): 2923, 2854, 1465, 1207, 1018, 721 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 3.95 (q, J = 6.6 Hz, 2 H), 1.72–1.64 (m, 6
H), 1.61–1.52 (m, 4 H), 1.41–1.22 (m, 30 H), 0.88 (t, J = 6.3 Hz, 9 H).
13C NMR (CDCl3, 100 MHz): δ = 64.1, 64.1, 32.0, 31.2, 31.0, 30.9, 29.4,
29.3, 29.3, 29.2, 28.6, 27.7, 25.8, 22.8, 22.1, 22.1, 14.2.
31P NMR (CDCl3, 162 MHz): δ = 57.8.
All reactions were carried out in oven-dried glassware under a N2 at-
mosphere. POCl3 (99%), octylmagnesium bromide (2.0 M in Et2O), (2-
ethylhexyl)magnesium bromide (1.0 M in Et2O), anhyd CdCl2 (99%), 1-
octanol (99%), and 1-dodecanol (98%) were purchased from Acros Or-
ganics. Dodecylmagnesium bromide (1.0 M in Et2O) and phenylmag-
nesium bromide (3.0 M in Et2O) were purchased from Sigma-Aldrich.
2-Ethyl-1-hexanol (99%) was purchased from Alfa Aesar, pyridine
(99.7%) was purchased from VWR and anhyd ZnCl2 (98–100%) was
MS (ESI): m/z = 403 [M + H]+, 425 [M + Na]+, 805 [2 M + H]+, 827
[2 M + Na]+.
Anal. Calcd for C24H51O2P: C, 71.59; H, 12.77. Found: C, 71.40; H,
12.66.
purchased from Chem-Lab. Anhyd Et2O was obtained using
a
MBRAUN SPS-800 system. For column chromatography, 0.060–0.200
mm (60 A) silica gel from Acros Organics was used as the stationary
phase. All chemicals were used as received without further purifica-
tion.
Dodecyl Didodecylphosphinate (1b)
Prepared according to the general phosphinate synthesis procedure
using anhyd Et2O (10 mL), dodecylmagnesium bromide (20 mL, 20
mmol, 2 equiv), and 1-dodecanol (4.5 mL, 20 mmol, 2 equiv). The re-
action with the Grignard reagent was stirred at r.t. for 24 h and the
reaction with the alcohol was stirred at r.t. for 24 h. After extractive
workup, the excess of 1-dodecanol was removed using a short-path
vacuum distillation apparatus at 300 °C. The resulting crude product
was purified by column chromatography (silica gel; CH2Cl2/EtOAc; 9:1
v/v), providing the pure compound as a white solid; yield: 3.16 g
(55%); mp 39–41 °C.
1H and 13C NMR spectra were recorded at r.t. in CDCl3 on a Bruker As-
cend 400 MHz instrument operating at a frequency of 400 MHz for
1H, 100 MHz for 13C and 162 MHz for 31P. 1H chemical shifts were ref-
erenced to TMS (0.00 ppm), 13C chemical shifts were referenced to the
CDCl3 solvent signal (77.16 ppm) and 31P chemical shifts were refer-
enced to aq 85% H3PO4 (0.00 ppm). Melting points were determined
on a Mettler-Toledo DSC882e instrument under a He atmosphere us-
ing a heating rate of 5 °C min–1. IR spectra were recorded on a Bruker
Vertex 70 ATR-FTIR spectrophotometer. Low-resolution mass spectra
were recorded on a Thermo Finnigan LCQ Advantage instrument (ESI
mode). CHN elemental analysis was performed on a Thermo Scientif-
ic Flash 2000 Organic Elemental Analyzer.
IR (ATR): 2916, 2848, 1463, 1184, 966, 773 cm–1
1H NMR (CDCl3, 400 MHz): δ = 3.95 (q, J = 6.6 Hz, 2 H), 1.75–1.61 (m, 6
H), 1.61–1.50 (m, 4 H), 1.40–1.22 (m, 54 H), 0.88 (t, J = 6.6 Hz, 9 H).
.
13C NMR (CDCl3, 100 MHz): δ = 64.1, 64.1, 32.1, 31.1, 31.0, 30.9, 29.8,
29.7, 29.7, 29.5, 29.5, 29.4, 29.3, 28.6, 27.7, 25.8, 22.8, 22.1, 22.1, 14.3.
Phosphinates 1; General Procedure
31P NMR (CDCl3, 162 MHz): δ = 57.8.
To an oven-dried 100 mL two-necked flask, fitted with a reflux con-
denser were added anhyd Et2O (amount depending on the concentra-
tion of the used Grignard reagent solution) and POCl3 (0.93 mL, 10
mmol, 1 equiv). The solution was cooled in an ice-salt mixture and a
Grignard reagent (20 mmol, 2 equiv) solution in Et2O was slowly add-
ed. After stirring with cooling for 30 min, the reaction mixture was
brought to r.t. and stirred for the indicated time. The mixture was
then cooled again in an ice-salt mixture and the alcohol (20 mmol, 2
equiv) and pyridine (1.8 mL, 22 mmol, 2.2 equiv) were slowly added.
Stirring with cooling for 5 min was followed by reaction at r.t. The re-
action was quenched after the indicated time by cooling in an ice-salt
mixture and adding sat. aq NH4Cl (5 mL). The crude mixture was then
poured into CH2Cl2 (100 mL), washed three times with dil HCl (1–2%,
100 mL in total), dried (MgSO4), filtered, and evaporated to dryness.
The excess of alcohol was removed using a short-path vacuum distil-
lation apparatus and the resulting crude product was purified by col-
umn chromatography.
MS (ESI): m/z = 571 [M + H]+, 593 [M + Na]+, 1142 [2 M + H]+, 1164
[2 M + Na]+, 1734 [3 M + Na].
Anal. Calcd for C36H75O2P: C, 75.73; H, 13.24. Found: C, 76.43; H,
13.17.
2-Ethylhexyl Bis(2-ethylhexyl)phosphinate (1c)
[CAS Reg. No. 36333-32-1]
Prepared according to the general phosphinate synthesis procedure
using anhyd Et2O (10 mL), (2-ethylhexyl)magnesium bromide (20 mL,
20 mmol, 2 equiv), and 2-ethyl-1-hexanol (3.1 mL, 20 mmol, 2 equiv).
The reaction with the Grignard reagent was stirred at r.t. for 18.5 h
and the reaction with the alcohol was stirred at r.t. for 3 days. After
extractive workup, the excess of 2-ethyl-1-hexanol was removed us-
ing a short-path vacuum distillation apparatus at 150 °C. The result-
ing crude product was purified by column chromatography (silica gel;
CH2Cl2/EtOAc; 95:5 v/v), providing the pure compound as a colorless
liquid; yield: 2.08 g (52%).
Octyl Dioctylphosphinate (1a)
IR (ATR): 2957, 2927, 1460, 1224, 1017, 820 cm–1
.
[CAS Reg. No. 7065-29-4]
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Synthesis
1H NMR (CDCl3, 400 MHz): δ = 3.92–3.79 (m, 2 H), 1.81–1.71 (m, 2 H),
1.66–1.60 (m, 4 H), 1.58–1.34 (m, 11 H), 1.34–1.16 (m, 14 H), 1.07–
0.69 (m, 18 H).
13C NMR (CDCl3, 100 MHz): δ = 66.0, 40.6, 40.5, 34.0, 33.9, 33.7, 32.8,
30.2, 29.1, 28.8, 28.7, 27.2, 27.1, 27.0, 23.6, 23.2, 23.1, 14.3, 14.2, 11.1,
10.5, 10.5.
MS (ESI): m/z = 403 [M + H]+, 425 [M + Na]+, 805 [2 M + H]+, 827
[2 M + Na]+.
Anal. Calcd for C24H51O2P: C, 71.59; H, 12.77. Found: C, 72.18; H,
12.78.
Dioctylphosphinic Acid (1f)
31P NMR (CDCl3, 162 MHz): δ = 57.6 (t, J = 9.9 Hz).
[CAS Reg. No. 683-19-2]
MS (ESI): m/z = 403 [M + H]+, 425 [M + Na]+, 805 [2 M + H]+, 827
To an oven-dried 100 mL two-neck flask, fitted with a reflux con-
denser were added anhyd Et2O (20 mL) and POCl3 (0.93 mL, 10 mmol,
1 equiv). The solution was cooled in an ice-salt mixture and octyl-
magnesium bromide (10 mL, 20 mmol, 2 equiv) was slowly added. Af-
ter stirring with cooling for 30 min, the reaction mixture was brought
to r.t. and stirred for 19.5 h. The mixture was then cooled again in an
ice-salt mixture, and H2O (5 mL) and pyridine (1.8 mL, 22 mmol, 2.2
equiv) were slowly added. Stirring with cooling for 5 min was fol-
lowed by reaction at r.t. for 7 h. The crude mixture was then poured
into CH2Cl2 (100 mL), washed three times with dil HCl (1–2%, 100 mL
in total), dried (MgSO4), filtered, and evaporated to dryness. The re-
sulting crude product was purified by recrystallization from hot hep-
tane (50 mL), filtered, and washed with pentane, providing the pure
compound as a white solid; yield: 1.52 g (52%); mp 83–84 °C.
[2 M + Na]+.
Anal. Calcd for C24H51O2P: C, 71.59; H, 12.77. Found: C, 71.81; H,
12.62.
Octyl Diphenylphosphinate (1d)
[CAS Reg. No. 3389-73-9]
Prepared according to the general phosphinate synthesis procedure
using anhyd Et2O (40 mL), phenylmagnesium bromide (6.7 mL, 20
mmol, 2 equiv), and 1-octanol (3.2 mL, 20 mmol, 2 equiv). The reac-
tion with the Grignard reagent was stirred at r.t. for 21.5 h and the
reaction with the alcohol was stirred at r.t. for 25.5 h. After extractive
workup, the excess of 1-octanol was removed using a short-path vac-
uum distillation apparatus at 250 °C. The resulting crude product was
purified by column chromatography (silica gel; CH2Cl2/EtOAc; 9:1
v/v), providing the pure compound as a slightly yellowish liquid;
yield: 1.45 g (44%).
IR (ATR): 2915, 2846, 1463, 967, 779 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 10.52 (s, 1 H), 1.71–1.52 (m, 8 H),
1.43–1.33 (m, 4 H), 1.33–1.20 (m, 16 H), 0.87 (t, J = 6.8 Hz, 6 H).
13C NMR (CDCl3, 100 MHz): δ = 32.0, 31.1, 31.0, 29.6, 29.3, 29.3, 28.7,
22.8, 21.7, 21.7, 14.2.
31P NMR (CDCl3, 162 MHz): δ = 60.4.
IR (ATR): 2925, 1438, 1227, 1129, 991, 727, 694, 560, 537 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.81 (ddd, J = 12.2, 8.2, 1.3 Hz, 4 H),
7.56–7.48 (m, 2 H), 7.49–7.40 (m, 4 H), 4.02 (q, J = 6.7 Hz, 2 H), 1.76–
1.68 (m, 2 H), 1.43–1.34 (m, 2 H), 1.33–1.22 (m, 8 H), 0.87 (t, J = 6.9
Hz, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 132.6, 132.2, 132.2, 131.9, 131.8,
131.2, 128.7, 128.6, 65.2, 65.2, 31.9, 30.7, 30.7, 29.3, 29.3, 25.8, 22.8,
14.2.
MS (ESI): m/z = 289 [M – H]–, 579 [2 M – H]–, 601 [2 M – 2 H + Na]–.
Anal. Calcd for C16H35O2P: C, 66.17; H, 12.15. Found: C, 66.67; H,
12.07.
Phosphonates 2; General Procedure
31P NMR (CDCl3, 162 MHz): δ = 31.3.
To an oven-dried 100 mL two-necked flask, fitted with a reflux con-
denser were added anhyd ZnCl2 (0.75 g, 5.5 mmol, 0.55 equiv) and an-
hyd Et2O (amount depending on the concentration of the used
Grignard reagent solution). The mixture was cooled in an ice-bath
and a Grignard reagent (10 mmol, 1 equiv) solution in Et2O was slow-
ly added. The reaction mixture was stirred 10 more min at 0 °C fol-
lowed by stirring at r.t. for the indicated time. The solution was then
cooled in an ice-salt mixture and POCl3 (0.93 mL, 10 mmol, 1 equiv)
was added. After stirring with cooling for 5 min, the mixture was
brought to r.t. and stirred for the indicated time. The mixture was
cooled again in an ice-salt mixture and the alcohol (30 mmol, 3 equiv)
and pyridine (2.7 mL, 33 mmol, 3.3 equiv) were slowly added. Stirring
with cooling for 5 min was followed by reaction at r.t. The reaction
was quenched after the indicated time by cooling in an ice-salt mix-
ture and adding dil HCl (1–2%, 5 mL). The crude mixture was then
poured into CH2Cl2 (100 mL), washed three times with dil HCl (1–2%,
100 mL in total), dried (MgSO4), filtered, and evaporated to dryness.
The excess of alcohol was removed using a short-path vacuum distil-
lation apparatus and the resulting crude product was purified by col-
umn chromatography.
MS (ESI): m/z = 331 [M + H]+, 353 [M + Na]+, 661 [2 M + H]+, 683
[2 M + Na]+.
Anal. Calcd for C20H27O2P: C, 72.70; H, 8.24. Found: C, 73.23; H, 8.36.
2-Ethylhexyl Dioctylphosphinate (1e)
[CAS Reg. No. 1400694-65-6]
Prepared according to the general phosphinate synthesis procedure
using anhyd Et2O (20 mL), octylmagnesium bromide (10 mL, 20
mmol, 2 equiv), and 2-ethyl-1-hexanol (3.1 mL, 20 mmol, 2 equiv).
The reaction with the Grignard reagent was stirred at r.t. for 20 h and
the reaction with the alcohol was stirred at r.t. for 24 h. After ex-
tractive workup, the excess of 2-ethyl-1-hexanol was removed using
a short-path vacuum distillation apparatus at 150 °C. The resulting
crude product was purified by column chromatography (silica gel;
CH2Cl2/EtOAc; 8:2 v/v), providing the pure compound as a slightly yel-
lowish liquid; yield: 2.35 g (58%).
IR (ATR): 2924, 2855, 1461, 1208, 1016, 811 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 3.90–3.81 (m, 2 H), 1.75–1.62 (m, 4 H),
1.61–1.50 (m, 5 H), 1.42–1.34 (m, 6 H), 1.33–1.22 (m, 22 H), 0.96–0.83
(m, 12 H).
13C NMR (CDCl3, 100 MHz): δ = 66.2, 66.1, 40.5, 40.5, 31.9, 31.1, 31.0,
30.2, 29.2, 29.2, 29.1, 28.5, 27.6, 23.6, 23.1, 22.8, 22.2, 22.1, 14.2, 14.2,
11.1.
Dioctyl Octylphosphonate (2a)
[CAS Reg. No. 7098-33-1]
Prepared according to the general phosphonate synthesis procedure
using anhyd Et2O (20 mL), octylmagnesium bromide (5 mL, 10 mmol,
1 equiv), and 1-octanol (4.7 mL, 30 mmol, 3 equiv). The correspond-
ing organozinc reagent was synthesized by stirring 2 h at r.t. The reac-
31P NMR (CDCl3, 162 MHz): δ = 57.6.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

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Synthesis
tion with the formed organozinc reagent was stirred at r.t. for 51 h
and the reaction with the alcohol was stirred at r.t. for 17 h. After ex-
tractive workup, the excess of 1-octanol was removed using a short-
path vacuum distillation apparatus at 200 °C. The resulting crude
product was purified by column chromatography (silica gel; CH2Cl2/
EtOAc; 95:5 v/v), providing the pure compound as a slightly yellowish
liquid; yield: 1.92 g (46%).
1H NMR (CDCl3, 400 MHz): δ = 3.98–3.85 (m, 4 H), 1.81–1.65 (m, 3 H),
1.55–1.50 (m, 2 H), 1.50–1.35 (m, 8 H), 1.35–1.17 (m, 16 H), 1.05–0.73
(m, 18 H).
13C NMR (CDCl3, 100 MHz): δ = 67.5, 67.4, 40.5, 40.4, 34.3, 34.3, 33.8,
33.7, 30.3, 30.2, 30.2, 29.1, 28.9, 28.7, 26.9, 26.8, 23.5, 23.5, 23.2, 23.1,
14.3, 14.2, 11.1, 10.5.
31P NMR (CDCl3, 162 MHz): δ = 32.9.
IR (ATR): 2923, 2854, 1465, 1248, 996, 722 cm–1
.
MS (ESI): m/z = 419 [M + H]+, 441 [M + Na]+, 837 [2 M + H]+, 859
1H NMR (CDCl3, 400 MHz): δ = 4.06–3.94 (m, 4 H), 1.77–1.53 (m, 10
H), 1.39–1.25 (m, 28 H), 0.88 (t, J = 6.4 Hz, 9 H).
13C NMR (CDCl3, 100 MHz): δ = 65.7, 65.6, 32.0, 31.9, 30.9, 30.8, 30.7,
[2 M + Na]+.
Anal. Calcd for C24H51O3P: C, 68.86; H, 12.28. Found: C, 69.30; H,
12.22.
30.7, 29.4, 29.3, 29.2, 26.4, 25.7, 25.0, 22.8, 22.6, 22.6, 14.2.
31P NMR (CDCl3, 162 MHz): δ = 32.8.
Dioctyl Phenylphosphonate (2d)
MS (ESI): m/z = 419 [M + H]+, 441 [M + Na]+, 837 [2 M + H]+, 859 [2 M
[CAS Reg. No. 1754-47-8]
+ Na]+.
Prepared according to the general phosphonate synthesis procedure
using anhyd Et2O (40 mL), phenylmagnesium bromide (3.3 mL, 10
mmol, 1 equiv), and 1-octanol (4.7 mL, 30 mmol, 3 equiv). The corre-
sponding organozinc reagent was synthesized by stirring 2 h at r.t.
The reaction with the formed organozinc reagent was stirred at r.t. for
21.5 h and the reaction with the alcohol was stirred at r.t. for 29 h.
After extractive workup, the excess of 1-octanol was removed using a
short-path vacuum distillation apparatus at 250 °C. The resulting
crude product was purified by column chromatography (silica gel;
CH2Cl2/EtOAc; 95:5 v/v), providing the pure compound as a slightly
yellowish liquid; yield: 0.55 g (14%).
Anal. Calcd for C24H51O3P: C, 68.86; H, 12.28. Found: C, 69.31; H,
12.24.
Didodecyl Dodecylphosphonate (2b)
Prepared according to the general phosphonate synthesis procedure
using anhyd Et2O (15 mL), dodecylmagnesium bromide (10 mL, 10
mmol, 1 equiv), and 1-dodecanol (6.7 mL, 30 mmol, 3 equiv). The cor-
responding organozinc reagent was synthesized by stirring 3 h at r.t.
The reaction with the formed organozinc reagent was stirred at r.t. for
46 h and the reaction with the alcohol was stirred at r.t. for 5 h. After
extractive workup, the excess of 1-dodecanol was removed using a
short-path vacuum distillation apparatus at 300 °C. The resulting
crude product was purified by column chromatography (silica gel;
CH2Cl2/EtOAc; 95:5 v/v), providing the pure compound as a white sol-
id; yield: 2.12 g (36%); mp 34–36 °C.
IR (ATR): 2924, 2855, 1439, 1251, 1131, 977, 748, 695, 564 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 7.87–7.74 (m, 2 H), 7.58–7.51 (m, 1 H),
7.51–7.42 (m, 2 H), 4.11–3.95 (m, 4 H), 1.71–1.62 (m, 4 H), 1.39–1.31
(m, 4 H), 1.31–1.20 (m, 16 H), 0.87 (t, J = 6.9 Hz, 6 H).
13C NMR (CDCl3, 100 MHz): δ = 132.5, 132.4, 132.0, 131.9, 129.5,
128.6, 128.5, 127.7, 66.3, 66.2, 31.9, 30.6, 30.6, 29.3, 29.2, 25.7, 22.8,
14.2.
IR (ATR): 2913, 2847, 1469, 1233, 992, 837, 718 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 4.08–3.91 (m, 4 H), 1.76–1.68 (m, 2 H),
1.67–1.62 (m, 4 H), 1.62–1.55 (m, 2 H), 1.42–1.16 (m, 54 H), 0.88 (t, J =
6.8 Hz, 9 H).
13C NMR (CDCl3, 150 MHz): δ = 65.6, 65.6, 32.1, 30.8, 30.8, 30.7, 30.7,
29.8, 29.8, 29.8, 29.7, 29.7, 29.6, 29.5, 29.4, 29.3, 26.2, 25.7, 25.2, 22.8,
22.6, 22.6, 14.3.
31P NMR (CDCl3, 162 MHz): δ = 18.9.
MS (ESI): m/z = 383 [M + H]+, 405 [M + Na]+, 765 [2 M + H]+, 787
[2 M + Na]+.
Anal. Calcd for C22H39O3P: C, 69.08; H, 10.28. Found: C, 69.94; H,
10.43.
31P NMR (CDCl3, 162 MHz): δ = 32.8.
MS (ESI): m/z = 558 [M + H]+, 610 [M + Na]+.
Bis(2-ethylhexyl) Octylphosphonate (2e)
Anal. Calcd for C36H75O3P: C, 73.67; H, 12.88. Found: C, 74.30; H,
12.82.
[CAS Reg. No. 52894-02-7]
Prepared according to the general phosphonate synthesis procedure
using anhyd Et2O (20 mL), octylmagnesium bromide (5 mL, 10 mmol,
1 equiv), and 2-ethyl-1-hexanol (4.7 mL, 30 mmol, 3 equiv). The cor-
responding organozinc reagent was synthesized by stirring 2 h at r.t.
The reaction with the formed organozinc reagent was stirred at r.t. for
24 h and the reaction with the alcohol was stirred at r.t. for 25 h. After
extractive workup, the excess of 2-ethyl-1-hexanol was removed us-
ing a short-path vacuum distillation apparatus at 150 °C. The result-
ing crude product was purified by column chromatography (silica gel;
CH2Cl2/EtOAc; 95:5 v/v), providing the pure compound as a slightly
yellowish liquid; yield: 1.82 g (43%).
Bis(2-ethylhexyl) (2-Ethylhexyl)phosphonate (2c)
[CAS Reg. No. 126-63-6]
Prepared according to the general phosphonate synthesis procedure
using anhyd Et2O (15 mL), (2-ethylhexyl)magnesium bromide (10 mL,
10 mmol, 1 equiv), and 2-ethyl-1-hexanol (4.7 mL, 30 mmol, 3 equiv).
The corresponding organozinc reagent was synthesized by stirring 2.5
h at r.t. The reaction with the formed organozinc reagent was stirred
at r.t. for 46.5 h and the reaction with the alcohol was stirred at r.t. for
21.5 h. After extractive workup, the excess of 2-ethyl-1-hexanol was
removed using a short-path vacuum distillation apparatus at 150 °C.
The resulting crude product was purified by column chromatography
(silica gel; CH2Cl2/EtOAc; 8:2 v/v), providing the pure compound as a
slightly yellowish liquid; yield: 1.77 g (42%).
IR (ATR): 2926, 2858, 1461, 1248, 1010, 863 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 3.98–3.84 (m, 4 H), 1.77–1.67 (m, 2 H),
1.63–1.50 (m, 4 H), 1.45–1.34 (m, 6 H), 1.33–1.20 (m, 20 H), 0.97–0.82
(m, 15 H).
IR (ATR): 2958, 2928, 1461, 1246, 1011, 869 cm–1
.
Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H

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B. Verbelen et al.
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Synthesis
13C NMR (CDCl3, 100 MHz): δ = 67.7, 67.6, 40.4, 40.4, 32.0, 30.8, 30.7,
30.1, 29.2, 29.2, 29.1, 26.2, 24.8, 23.5, 23.5, 23.1, 22.8, 22.7, 22.6, 14.2,
14.2, 11.1.
(2) (a) Jain, P.; Choudhary, V.; Varma, I. K. J. Macromol. Sci., Polym.
Rev. 2002, 42, 139. (b) Lu, S.-Y.; Hamerton, I. Prog. Polym. Sci.
2002, 27, 1661. (c) Braun, U.; Balabanovich, A. I.; Schartel, B.;
Knoll, U.; Artner, J.; Ciesielski, M.; Döring, M.; Perez, R.; Sandler,
J. K. W.; Altstädt, V.; Hoffmann, T.; Pospiech, D. Polymer 2006,
47, 8495. (d) Levchik, S. V.; Weil, E. D. In Advances in Fire Retar-
dant Materials: Developments in Phosphorus Flame Retardants;
Horrocks, A. R.; Price, D., Eds.; Woodhead Publishing Limited:
Cambridge, 2008, 41–66.
31P NMR (CDCl3, 162 MHz): δ = 32.7.
MS (ESI): m/z = 419 [M + H]+, 441 [M + Na]+, 837 [2 M + H]+, 859
[2 M + Na]+.
Anal. Calcd for C24H51O3P: C, 68.86; H, 12.28. Found: C, 69.27; H,
12.14.
(3) (a) Flett, D. S. J. Organomet. Chem. 2005, 690, 2426. (b) Xie, F.;
Zhang, T. A.; Dreisinger, D.; Doyle, F. Miner. Eng. 2014, 56, 10.
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Langmuir 1996, 12, 6429. (b) Guerrero, G.; Mutin, P. H.; Vioux,
A. Chem. Mater. 2001, 13, 4367.
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Octylphosphonic Acid (2f)
[CAS Reg. No. 4724-48-5]
To an oven-dried 100 mL two-neck flask, fitted with a reflux con-
denser were added anhyd ZnCl2 (0.75 g, 5.5 mmol, 0.65 equiv) and
anhyd Et2O (20 mL). The mixture was cooled in an ice-bath and octyl-
magnesium bromide (4.2 mL, 8.4 mmol, 1 equiv) was slowly added.
The reaction mixture was stirred 10 more min at 0 °C followed by 2 h
at r.t. The solution was then cooled in an ice-salt mixture and POCl3
(0.78 mL, 8.4 mmol, 1 equiv) was added. After stirring with cooling
for 5 min, the mixture was brought to r.t. and stirred for 20 h. The
mixture was cooled again in an ice-salt mixture and H2O (5 mL) was
slowly added. Stirring with cooling for 5 min was followed by reac-
tion at r.t. for 25.5 h. The crude mixture was then poured into CH2Cl2
(100 mL), washed three times with dil HCl (1–2%, 100 mL in total),
dried (MgSO4), filtered, and evaporated to dryness. The resulting
crude product was purified by recrystallization from hot heptane (50
mL), filtered and washed with pentane, providing the pure compound
as a white solid; yield: 0.49 g (30%); mp 100–102 °C.
IR (ATR): 2918, 1468, 1106, 994, 943, 778, 715 cm–1
.
1H NMR (CDCl3, 400 MHz): δ = 9.53 (s, 2 H), 1.81–1.68 (m, 2 H), 1.68–
1.55 (m, 2 H), 1.41–1.33 (m, 2 H), 1.33–1.22 (m, 8 H), 0.88 (t, J = 6.8
Hz, 3 H).
13C NMR (CDCl3, 100 MHz): δ = 31.9, 30.7, 30.5, 29.2, 29.2, 26.1, 24.7,
22.8, 22.2, 22.1, 14.2.
31P NMR (CDCl3, 162 MHz): δ = 37.7.
(11) (a) Palacios, F.; Alonso, C.; de los Santos, J. M. Chem. Rev. 2005,
105, 899. (b) Tappe, F. M. J.; Trepohl, V. T.; Oestreich, M. Synthe-
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65.
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S.; Schwabacher, A. W. Synthesis 1992, 1255.
MS (ESI): m/z = 193 [M – H]–, 387 [2 M – H]–, 581 [3 M – H]–, 603
[3 M – 2 H + Na]–, 797 [4 M – 2 H + Na]–.
Anal. Calcd for C8H19O3P: C, 49.48; H, 9.86. Found: C, 49.19; H, 9.71.
(13) Kosolapoff, G. M. Org. React. 1951, 6, 273.
Funding Information
(14) Bhattacharya, A. K.; Thyagarjan, G. Chem. Rev. 1981, 81, 415.
(15) (a) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. Synthesis
1981, 56. (b) Lu, X.; Zhu, J. Synthesis 1987, 726.
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(b) Kosolapoff, G. M. J. Am. Chem. Soc. 1950, 72, 5508.
(17) Van Lindhoudt, J. P.; Van den Berghe, E. V.; Van der Kelen, G. P.
Spectrochim. Acta, A 1979, 35, 1307.
The research leading to these results received funding from the Euro-
pean Research Council (ERC) under the European Union’s Horizon
2020 Research and Innovation Program: Grant Agreement 694078 –
Solvometallurgy for critical metals (SOLCRIMET).
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Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609435.
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Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–H