An efficient method for the preparation of silyl esters of diphosphoric, phosphoric, and phosphorous acid

Article abstract of DOI:10.1016/j.poly.2013.12.024

Tetrakis(trialkylsilyl) diphosphate (alkyl = Me, Et, iPr, tBu) can be obtained in quantitative yield by reacting commercial disodium dihydrogen diphosphate with the respective trialkyl chlorosilane in a triphasic system with formamide. The alkylsilane residues of the diphosphate silyl esters can be either partially or completely hydrolyzed without concurrent cleavage of the P-O-P bond of the diphosphate moiety. The method can be expanded to efficiently produce other persilylated or partially silylated phosphates and phosphites.

Full text of DOI:10.1016/j.poly.2013.12.024

Polyhedron 70 (2014) 133–137
Contents lists available at ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
An efficient method for the preparation of silyl esters of diphosphoric,
phosphoric, and phosphorous acid
⇑
Ludger A. Wessjohann , Marco A. Dessoy
Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Tetrakis(trialkylsilyl) diphosphate (alkyl = Me, Et, iPr, tBu) can be obtained in quantitative yield by
reacting commercial disodium dihydrogen diphosphate with the respective trialkyl chlorosilane in a
triphasic system with formamide. The alkylsilane residues of the diphosphate silyl esters can be either
partially or completely hydrolyzed without concurrent cleavage of the P–O–P bond of the diphosphate
moiety. The method can be expanded to efficiently produce other persilylated or partially silylated
phosphates and phosphites.
Received 30 September 2013
Accepted 22 December 2013
Available online 31 December 2013
Keywords:
Silylations
Diphosphates
Protective groups
Hydrolysis
Ó 2014 Elsevier Ltd. All rights reserved.
Phosphate esters
Triphasic system
1. Introduction
thyldisiloxane. In an early account, Mileshkevich and Karlin re-
ported the isolation of 2a in up to 18% from crude PPSE [9]. The
The diphosphate moiety comprehends a critical structural ele-
ment in a series of important biological metabolites and cofactors
(i.e. diphosphorylated terpenols, sugars, nucleotides, and nicoti-
neamide-based dinucleotides) which play central roles in both pri-
mary and secondary metabolisms of all living organisms. Silylated
derivatives of diphosphoric acid are potential precursors for the
chemical synthesis of these biologically relevant molecules. Tetra-
alkyl diphosphates (alkyl = Et, nPr, iPr, nBu) were shown to be toxic
to some organisms [1]. E.g., tetraethyl diphosphate was used as a
pesticide [2], as it expresses powerful anticholinesterase activity
with actions similar to eserine and neostigmine [3]. Tetrabenzyl
diphosphate has been used for the phosphorylation of inositol
authors, though, did not provide a definitive proof of structure
and purity of the isolated product at that time. Later, Yamamoto
and Watanabe disclosed the composition of crude PPSE by means
of 31P NMR spectroscopy [10]. According to the latter authors,
the share of 2a in the crude product mixture is somewhat influ-
enced by the reaction conditions, but in no case it has been found
to be higher than 7%. Similarly, the silyl ester 2a also forms in ca.
6% yield upon treatment of phosphorus pentoxide with hexameth-
yldisilazane [11].
The direct reaction of (nucleophilic) inorganic diphosphate and
(electrocphilic) activated trialkylsilyl compounds, e.g. TMS-chlo-
ride, does not work without solvent mediation. All solvents com-
monly applied for such reactions either do not further the
reaction, e.g. they are unable to dissolve the diphosphate, or they
react with the activated TMS or with the product with its sensitive
(activated) P–O–P or Si–O–P bonds. Furthermore, active strong acid
or nucleophiles deteriorate the product, sometimes even catalyti-
cally. Isolation of the products thus was a major challenge not
yet tackled. The stability of sterically hindered higher silyl esters
is expected to be better, but they also promise less applicability
at a much higher price.
derivatives (e.g. D-myo-inositol-1,4,5-trisphosphate a cellular sec-
ond messenger) [4–6] and in the synthesis of (À)-5-enolpyruvyl-
shikimate-3-phosphate (a principle metabolite in the shikimic
acid pathway) [7]. Trimethylsilyl (TMS) esters of a series of oxya-
nions of main group elements have been synthesized and spectro-
scopically studied in the past [8]. However, the effective silylation
of diphosphoric acid or its salts on preparative scale to give pure
product has not been reported until now. Formation has been ob-
served in different reaction systems. Thus, tetrakis(trimethylsilyl)
diphosphate (2a) is formed as a byproduct in the preparation of
polyphosphoric acid trimethylsilyl ester (PPSE). PPSE is obtained
from phosphorus pentoxide upon reaction with excess hexame-
To the best of our knowledge, the only example of a purpose-
ful preparation of a diphosphate silyl ester is given by Mawhin-
ney [12]. Accordingly, both diphosphoric acid and its
ammonium salt were converted into tetrakis(tert-butyldimethyl-
silyl) diphosphate (2d) with N-methyl-N-(tert-butyldimethylsilyl)
trifluoroacetamide in N,N-dimethylformamide (DMF). The silyl es-
⇑
Corresponding author. Tel.: +49 345 5582 1301; fax: +49 345 5582 1309.
E-mail address: wessjohann@ipb-halle.de (L.A. Wessjohann).
0277-5387/$ - see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2013.12.024

134
L.A. Wessjohann, M.A. Dessoy / Polyhedron 70 (2014) 133–137
ter 2d, however, was prepared for analytical purposes in no more
than a few micro-grams and has not been isolated from the crude
reaction mixture. Unfortunately, silyl protected diphosphates are
also unavailable by an inverse approach starting from (electro-
philic) diphosphoryl chloride and nucleophiles (like R3SiOÀ) be-
cause these cleave the P–O–P bond rather than the P–Cl bond
[13,14].
The claim of Nifant’ev et al. to have synthesized 2a in 44% yield
from bis(trimethylsilyl) phosphite (4a) via a Todd-Atherton-like
reaction could not be verified (v.i.) [15]. In reality, the authors ob-
tained tris(trimethylsilyl) phosphate (4b, d 31P NMR = À24.8 ppm)
and have erroneously assigned the structure of this compound to
2a.
5 mmol), formamide (5 mL), and the corresponding trialkylsilyl
chloride (20 mmol) is added. The ternary system is vigorously stir-
red at 55 °C during the time (time intervals for 2b–2d: 4, 10 and
5 h, respectively). Petrol ether (20 mL) is added and stirring is con-
tinued for ca. 5 min. The clear top layer is transferred into a second
dry 50 mL Schlenk-tube and the solvent is evaporated under re-
duced pressure (ca. 12 mbar or lower, depending on the silylether
formed) at 40 °C.
2.2.2.1. Tetrakis(triethylsilyl) diphosphate 2b. 3.05 g (96%) of a vis-
cous, colorless liquid. 1H NMR (CDCl3, 400 MHz, d, ppm): 0.74 (q,
3
3JHH = 7.8 Hz, 24H, CH2), 0.97 (t, JHH = 7.8 Hz, 36H, CH3). 13C NMR
Herein we wish to report the first efficient synthesis of a series
of diphosphate trialkylsilyl esters (2a–2d) and improved access to
silylphosphate and silylphosphite.
(CDCl3, 100 MHz, d, ppm): 5.14 (CH3), 6.31 (CH2). 31P NMR (CDCl3,
162 MHz, d, ppm): À30.59 (s). 29Si NMR (CDCl3, 99 MHz, d, ppm):
2,4
25.77 (bt,
J
SiP
ꢀ 3.6 Hz). HRMS: calculated for C24H61O7P2Si4
[M+H]+: 635.29641, found: 635.29729.
2. Experimental
2.2.2.2. Tetrakis(triisopropylsilyl) diphosphate 2c. 3.8 g (95%) of a
highly viscous, colorless liquid. 1H NMR (CDCl3, 400 MHz, d,
2.1. Materials and methods
3
3
ppm): 1.11 (d, JHH = 7.4 Hz, 72H, CH3), 1.23 (hep, JHH = 7.4 Hz,
Formamide (cat. No. 47670), chlortrimethylsilane (cat. No.
92361), chlorotriethylsilane, chlortriisoproylsilane, chlordimeth-
yl-tert-butylsilane, and pyridine (cat. No. 82704) were purchased
from Fluka. P.a. grade H2Na2O7P2 was purchased either from Fluka
(cat. No. 71501) or Aldrich (cat. No. 34,073-1) [the amount of phos-
phate impurity correlates directly with the later amount of impu-
rity of silylated phosphate]. Petrol ether (b.p. 40–60 °C, Roth) was
used as received. 1H, 13C and 31P NMR spectra were recorded on
a Varian Mercury 400 spectrometer, operating at 400, 100, and
162 MHz, respectively. 29Si NMR spectra were recorded on a Varian
Inova 500 spectrometer, at an operational frequency of 99 MHz.
Unless otherwise stated, the spectra were recorded in CDCl3. 1H,
13C and 29Si NMR spectra were referenced to tetramethylsilane
(TMS, d = 0 ppm, s = singlet, d = doublet, t = triplet, bt = broad trip-
let, q = quartet, hep = heptet). 31P NMR spectra were externally ref-
erenced to an 85% H3PO4 capillary (d = 0 ppm). High-resolution
mass spectra were recorded with a Bruker BioApex 70e FT-ICR
(Bruker Daltonics, USA) and low-resolution mass spectra (MS-
ESI) were recorded with an API 150Ex (Applied Biosystems) mass
spectrometer, equipped with a turbo ion spray source.
12H, CH). 13C NMR (CDCl3, 100 MHz, d, ppm): 12.65 (CH), 17.12
(CH3). 31P NMR (CDCl3, 162 MHz, d, ppm): À32.81. 29Si NMR
2,4
(CDCl3, 99 MHz, d, ppm): 20.91 (t,
J
ꢀ 10.0 Hz). HRMS: calcu-
SiP
lated for C36H85O7P2Si4 [M+H]+: 803.48421, found: 803.48613.
2.2.2.3. Tetrakis(tert-butyldimethylsilyl) diphosphate 2d. 3.01 g (94%)
as a white, amorphous solid. 1H NMR (CDCl3, 400 MHz, d, ppm):
0.25 (s, 3H, CH3), 0.26 (s, 3H, CH3), 0.91 (s, 9H, C(CH3)3). 13C NMR
3
(CDCl3, 100 MHz, d, ppm): À4.01 (d, JCP = 3.8 Hz, CH3), 17.98
(C(CH3)3), 25.27 (C(CH3)3). 31P NMR (CDCl3, 162 MHz, d, ppm):
2,4
À30.02. 29Si NMR (CDCl3, 99 MHz, d, ppm): 25.98 (bt,
J
SiP
-
ꢀ 3.6 Hz). HRMS: calculated for
C
24H61O7P2Si4 [M+H]+:
635.29641, found: 635.29802.
2.3. General procedure for the preparation of 4a and 4b
To a dry, nitrogen flushed 100 mL Schlenk-tube containing a
solution of phosphorous acid (1.64 g, 20 mmol for the synthesis
of 4a) [or potassium dihydrogen phosphate (2.72 g, 20 mmol for
the synthesis of 4b)] in formamide (10 mL) trimethylsilyl chloride
(5.4 g, 50 mmol) is added. The resulted binary (4a) or ternary sys-
tem (4b) was vigorously stirred (caution: exothermic reaction, HCl
gas formation). After 1 h stirring, petrol ether (40 mL) was added
and stirring was continued for ca. 5 min. The top, clear layer of
the new binary or ternary system was transferred to a dry 50 mL
Schlenk-tube, and the solvent as well as excess TMSCl and
TMS–O–TMS were evaporated off under reduced pressure (ca.
12 mbar) at 40 °C.
2.2. Synthesis of tetrakis(trialkylsilyl) diphosphate esters 2a–2d
2.2.1. Tetrakis(trimethylsilyl) diphosphate 2a
A 250 mL dry flask was loaded with finely powdered dihydro-
gen disodium diphosphate (22.2 g, 0.1 mol), formamide (50 mL),
and under vivid stirring by trimethylsilyl chloride (45.5 g,
0.44 mol). Refluxing TMSCl must be cooled for larger scale synthe-
sis (caution: exothermic reaction with hydrogenchloride gas evolv-
ing!). After 1 h of stirring, petrol ether (200 mL) was added and
stirring was continued for ca. 5 min. The clear top layer was trans-
ferred into a dry 250 mL Schlenk-tube and the solvent as well as
excess TMSCl were evaporated off under reduced pressure (ca.
12 mbar) at 40 °C to give 46 g (100%) of the title compound as an
colorless liquid. 1H NMR (CDCl3, 400 MHz, d, ppm): 0.24 (s, CH3).
13C NMR (CDCl3, 100 MHz, d, ppm): 0.60 (s, CH3). 31P NMR (CDCl3,
2.3.1. Bis(trimethylsilyl) phosphite 4a [18]
Yield 4.41 g (97%), colorless liquid. 1H NMR (CDCl3, 400 MHz, d,
1
ppm): 0.22 (s, 9H, CH3), 6.75 (d, JHP = 700 Hz, 1H, PH). 13C NMR
3
(CDCl3, 100 MHz, d, ppm): 0.72 (d, JCP = 1.6 Hz, CH3). 31P NMR
162 MHz, d, ppm): À30.76 (s). 29Si NMR (CDCl3, 99 MHz, d, ppm):
1
(CDCl3, 162 MHz, d, ppm): À13.07 (d, JPH = 700 Hz, CH3). MS(ESI):
2,4
227 [M+H]+.
24.6 (t,
J
SiP
ꢀ 2.8 Hz); HRMS: calculated for C12H37O7P2Si4
[M+H]+: 467.10861, found: 467.10860.
2.2.2. General procedure for the preparation of tetrakis(trialkylsilyl)
diphosphate esters 2b–2d
A 50 mL dry Schlenk tube flushed with dry nitrogen is loaded
with finely powdered dihydrogen disodium diphosphate (1.11 g,
2.3.2. Tris(trimethylsilyl) phosphate 4b [9,17,19]
Yield 6.20 g (98%), colorless liquid. 1H NMR (CDCl3, 400 MHz, d,
ppm): 0.19 (s, 9H, CH3). 13C NMR (CDCl3, 100 MHz, d, ppm): 0.44 (d,
3JCP = 1.5 Hz, CH3). 31P NMR (CDCl3, 162 MHz, d, ppm): À25.11.

L.A. Wessjohann, M.A. Dessoy / Polyhedron 70 (2014) 133–137
135
amide. The use of these solvents, though, is quite disadvantageous
because the reaction is rather sluggish and product isolation
proved to be extremely difficult.
3. Results and discussion
3.1. Synthesis of tetrakis(trimethylsilyl) diphosphate ester 2a
3.2. Synthesis of tetrakis(trialkylsilyl) diphosphate esters 2b–2d
Disodium dihydrogen diphosphate (1) is quantitatively con-
verted into tetrakis(trimethylsilyl) diphosphate (2a, Scheme 1)
when treated with trimethylsilyl chloride (TMSCl) in formamide.
The use of the highly polar formamide as solvent is crucial for
the accomplishment of the reaction and subsequent product isola-
tion. While the very high polarity of formamide ensures the partial
solubilization of inorganic diphosphate 1, this property renders the
rather apolar TMSCl immiscible in this solvent. Consequently, the
resulting reaction mixture constitutes a ternary system of one solid
and two liquid phases. Nevertheless, the heterogeneous mixture
displays high reactivity if inorganic diphosphate 1 is used in a fi-
nely powdered form. If these criteria are met, an exothermic reac-
tion with HCl formation quickly sets in with the temperature rising
to 60 °C, forcing the TMSCl to gently reflux on the walls of the reac-
tion vessel (or condenser in larger setups) for a few minutes. The
reaction is completed within 1 h. A small excess (ca. 10%) of TMSCl
is routinely used in order to ensure the complete conversion of 1
into 2a. Taking this measure, initially no special caution concerning
moisture exclusion has to be taken, i.e. drying of glassware is not
required for the reaction, but eventually the product formed is
highly sensitive to the presence of moisture.
The protocol that has been developed for the synthesis of 2a
also can be applied for the synthesis of the bulkier trialkylsilyl
diphosphate esters 2b–2d (Scheme 1). The preparation of these
compounds, though, requires somewhat more elaborate reaction
conditions. The difficulties arise from the fact that the trialkylsilyl
chlorides required as starting materials as well as the correspond-
ing hexaalkyl disiloxanes and/or trialkyl silanols eventually formed
through concurrent hydrolysis have relatively high boiling points.
Thus, they cannot be separated from the respective diphosphate
esters as easily as in the case of 2a. Therefore, the reactions should
be conducted under strict moisture exclusion and the amounts of
the trialkylsilyl chloride used should be as close as possible to
stoichiometry.
The bulkier trialkylsilyl chlorides are expectedly less reactive
than TMSCl, thus longer reaction times and heating is required.
The shielded diphosphates 2b–2d are much less susceptible to
the cleavage of the P–O–P bond, and the HCl-catalyzed decomposi-
tion to the corresponding phosphate silylester under reaction con-
ditions is less pronounced than for 2a. Therefore these silylations
also can be conducted in the absence of pyridine. The isolation of
the esters 2b–2d by alkane extraction proceeds analogously to
the isolation of 2a. The former esters, though, are not as pure as
the latter. Besides the discussed tris(trialkylsilyl) phosphate, the
bulkier esters 2b–2d can be contaminated (<5%) with a diphos-
phate species that is silylated only threefold, i.e. possessing one
free OH-group, and with the corresponding silanols or
bissilylethers.
Given the high polarity of formamide, which renders products
2a insoluble in this solvent, product isolation/purification is an
exceptionally easy task. Straightforward extraction with ordinary
petrol ether (equally immiscible with formamide) gives an alkane
layer that is separated and the solvent is evaporated under reduced
pressure. In larger batches even direct separation of the pure prod-
uct is possible, without the help of alkane extraction. Excess TMSCl
and hexamethyl disiloxane, which is eventually formed in conse-
quence of the partial hydrolysis of TMSCl, are equally eliminated
during solvent evaporation. Following this simple procedure, the
silylated diphosphate is obtained in a highly pure form. The only
measurable impurity of 2a is tris(trimethylsilyl) phosphate (1% to
up to 5%), which is mainly formed by the silylation of the phos-
phate-contamination already present in the diphosphate salt 1,
i.e. the purity of the starting material is directly reflected in the
product. Nevertheless, the reaction should not be extended over
1 h in order to avoid product decomposition. Upon extended reac-
tion, the free HCl probably induces the decomposition of 2a. When
the reaction is performed in the presence of a stoichiometric
amount of pyridine (2 mmol pyridine per 1 mmol 1) no decompo-
sition of 2a is observed. One should be aware of the fact that in the
presence of pyridine, the reaction time increases to ca. 2.5 h.
Crude tetrakis(trimethylsilyl) diphosphate (2a) is a colorless li-
quid with a shelf life of only a few days at room temperature. Shelf
life increases with better removal of HCl traces. 2a dissolved in pet-
rol ether is stable for several weeks at room temperature, if the HCl
liberated during the reaction is removed under reduced pressure
prior to storage, e.g. by distillation of the petrol ether obtained
after the extraction. HCl-free, neat 2a is stable for months when
stored at À30 °C.
3.3. NMR spectroscopy
The 1H, 13C, 31P and 29Si NMR spectroscopic data sets recorded
for the esters 2a–2d are summarized in the Experimental section.
All synthesized diphosphate esters (2a–2d) delivered satisfactory
high-resolution mass spectrometric data.
The trialkylsilyl groups of the trialkylsilyl diphosphate esters 2a,
2b, and 2d can be fully hydrolyzed in aqueous base, leading to inor-
ganic diphosphate and the corresponding hexaalkyl disiloxanes or
trialkyl silanols. The rather labile P–O–P anhydride bond is not
markedly affected during this process [13,14]. As expected, the
hydrolysis rate declines with the bulkiness of the trialkylsilyl
group.
The hydrolysis of the trimethylsilyl groups of 2a is almost
instantaneous at 4 °C and pH 10, whereas the full hydrolysis of
the triethylsilyl groups of 2b takes ca. 30 min and that of the
tert-butyl-dimethylsilyl groups of 2d takes a few hours (at room
temperature). At pH 4–5 and room temperature, the tert-butyl-
dimethylsilyl groups of 2d are not completely cleaved even after
18 h. Hydrolysis of the even bulkier triisopropylsilyl groups of 2c
is not complete even after 30 h at room temperature and pH 10.
The partial hydrolytic cleavage of the trialkylsilyl groups of trial-
kylsilyl diphosphate esters is also possible. In order to achieve this,
they have to be treated with a defined amount of water in a water-
miscible solvent. Fig. 1b shows the 31P NMR spectrum of a mixture
containing 0.74 mmol of 2a and 0.36 mmol of water in
DMSO/CH3CN (4 mL) at 23 °C.
Disodium dihydrogen diphosphate (1) can also be persilylated
with TMSCl in polar solvents like pyridine or N,N-dimethyl form-
In contrast to the single, sharp line displayed by 2a (Fig. 1a), this
spectrum presents very broad bands, indicating that various chem-
ical identities are in a very fast dynamic equilibrium showing 31P
signals of –OPO(OTMS)2, –OPO(OH)(OTMS), and –OPO(OH)2 from
high to low field in the statistical ratio 1:2:1 expected from the
Scheme 1. Synthesis of tetrakis(trimethylsilyl) diphosphates.

136
L.A. Wessjohann, M.A. Dessoy / Polyhedron 70 (2014) 133–137
Fig. 1. 31P NMR spectrum of: (a) Compound 2a at 100 MHz in petroleum ether; (b)
2a (0.74 mmol) and water (0.36 mmol, one water molecule cleaves two TMS groups
[10]) in DMSO/CH3CN 3:1 (4 mL) at 160 MHz and 23 °C. (P = silylated phosphate
species, PP = silylated diphosphate species).
maximum equilibration for an average of semihydrolized 2a, i.e.
P2O(OTMS)2(OH)2 (3a). This equilibrium is a consequence of the
pronounced migratory aptitude exhibited by the TMS group [10],
which has been compared to the mobility of a proton [16].
The fast dynamic equilibrium displayed between tetrakis(trim-
ethylsilylated) diphosphate 2a and the (partially) hydrolyzed tris
and eventually bis(trimethylsilylated) diphosphate 3a (Scheme 2
and Fig. 1b) can be ‘‘freeze-framed’’ if the analogous but less reac-
tive tetrakis(triethylsilyl)diphosphate (2b) is submitted to the
same hydrolytic treatment yielding bis(triethylsilylated) diphos-
phate 3b (Fig. 2). This reaction system evolves to the equilibrium
as depicted in Fig. 2 in two phases. First, each water molecule
quickly (ca. 15 min) cleaves one triethylsilyl-group from 2b to pre-
dominantly give rise to a mono desilylated derivative of 2b. Then,
the just formed triethylsilanol slowly (over a period of ca. 67 h)
cleaves off a second triethylsilyl-group from 2b and/or from the
mono desilylated derivative thereof, leading to the formation of
hexaethyl disiloxane, along with mono-, symmetrically bi-, and
asymmetrically bi- and/or threefold desilylated derivatives of 2b.
Due to the fact that the migratory aptitude of the triethylsilyl-
group is much less pronounced than that of the TMS group, the
half-life of each partially desilylated species in the equilibration
mixture is long enough to give rise to distinct resonance lines
(3JP,P) in the 31P NMR spectrum, as depicted in Fig. 2. The cleavage
of each trialkylsilyl group causes a downfield shift of ca. 10 ppm on
the affected phosphate moiety whereas the chemical shift of the
distant phosphate moiety remains almost unchanged. The partially
silylated diphosphoric acid species originating from partial desily-
lation of 2a and 2b can be neutralized with amines. Tertiary alkyl
amines like triethyl amine or diethyl isopropyl amine form salts,
which are highly soluble in polar solvents like acetone, acetonitrile,
N,N-dimethyl formamide, dimethyl sulfoxide, etc. Salts carrying
ammonium ions derived from aromatic or aliphatic primary and
secondary amines or from pyridine are only soluble in highly polar
Fig. 2. (a) 31P NMR spectrum of (TES)4P2O5 2b in petroleum ether at 160 MHz; and
31P NMR spectra of a mixture of 2b (0.78 mmol) and water (0.39 mmol, one water
molecule cleaves two TES groups) in DMSO/CH3CN 3:1 (3 mL) at 23 °C after, (b)
15 min; (c) 10 h; (d) 36 h; (e) 67 h. Spectra from (a) to (e) are each offset by ca.
À0.9 ppm in relation to the preceding one. [P = silylated phosphate species,
PP = (partially) silylated diphosphate species].
solvents like N,N-dimethyl formamide or dimethyl sulfoxide and
tend to precipitate in less polar solvents like acetone or acetoni-
trile. The salts, of which some in principle have potential as ionic
liquids, unfortunately are rather unstable and often decompose
within a few days at room temperature.
3.4. Synthesis and reactivity of silylesters of phosphite 4a and
phosphate 4b
As shown in Scheme 3, the new method for the synthesis of silyl
diphosphate esters 2a–2d described above is also splendidly suited
to accomplish improved and straightforward synthesis of known
bis(trimethylsilyl) phosphite (4a) [18] and tris(trimethylsilyl)
phosphate (4b) [9,17,19]. The advantages of this new reaction sys-
tem over the reported methods for the preparation of both 4a [18]
and 4b [9,17,19] are: (a) excellent yields combined with short reac-
tion times; (b) simple apparatus set up; and (c) an uncomplicated
product isolation and purification protocol allowing to obtain ana-
lytically pure products in only one reaction step without the need
Scheme 2. Partial hydrolysis of silyldiphosphate esters 2a (R = Me) and 2b (R = Et).
Scheme 3. Synthesis of silylesters of phosphite 4a and phosphate 4b.

L.A. Wessjohann, M.A. Dessoy / Polyhedron 70 (2014) 133–137
137
to purify intermediates or the final products (4a and 4b) by trou-
blesome distillation. It is worth to note that the homogeneous mix-
ture of phosphorous acid and trimethylsilyl chloride does not
undergo any reaction at room temperature. Upon the addition of
formamide an exothermic reaction sets in leading to the formation
of 3a. Thus, formamide must have a catalytic effect on the silyla-
tion reactions described herein, probably comparable to that dis-
played by N,N-dimethylformamide in the conversion of
carboxylic acids into the corresponding acylchlorides upon reac-
tion with thionyl chloride [20].
tion. The neutralization of the acidic hydroxyls formed as a result
of the partial desilylation with tertiary alkyl amines leads to the
formation of the corresponding organic solvent soluble trialkylam-
monium salts. These facts make the silylated diphosphates poten-
tial reagents for the preparation of both further organic and
inorganic diphosphates as well as for the silylation of further oxya-
nions derived either from main group elements, transition metals,
or organic oxo compounds.
Acknowledgements
The Todd-Atherton reaction has been reported as a suitable
method for the conversion of the phosphite 4a into the silyl
diphosphate ester 2a in moderate yields (44%) [12,13]. Accord-
ingly, a compound showing a 31P NMR resonance at À24.8 ppm
has been isolated and its structure was assigned to 2a. As we and
others have found [8], a chemical shift in the indicated range is
rather due to the phosphate ester 4b than to diphosphate 2a (dP
À30.76 ppm, in CDCl3). In view of this divergence, we reacted equi-
molar amounts of the phosphite, tetrachloromethane, and triethyl-
amine as reported [12,13]. In sequence, the crude product mixture
was diluted with petrol ether. An aliquot of the clear supernatant
obtained after short centrifugation was then combined with CDCl3
(1:1 v/v) and the sample subjected to 31P NMR measurement. The
31P NMR spectrum shows three major signals, with the following
relative intensities: dP À30.53 ppm (ca. 8%); dP À24.76 ppm (ca.
47%); dP À16.05 ppm (ca. 40%). The addition of authentic 2a caused
an increase on the intensity of the high-field signal (À30.53 ppm),
whereas the addition of authentic 4b amplified the signal at
À24.76 ppm. In addition, the hydrolyzate of the crude reaction
mixture gave inorganic phosphate as the main component, and
only a very minor amount of inorganic diphosphate and other
unidentified phosphorous compounds. Based on these observa-
tions, it can be concluded that, opposing earlier claims [15], the
Todd-Atherton reaction is unsuitable for the effective conversion
of phosphite 4a into diphosphate 2a.
We thank Prof. Dr. Stefan Berger (Institute of Analytical Chem-
istry, University of Leipzig) and Dr. A. Porzel (Leibniz Institute of
Plant Biochemistry) for the recording of the 31P decoupled and
29Si NMR spectra of compound 2d. M.A.D. thanks the German Aca-
demic Exchange Service (DAAD) for a PhD grant. Part of this work
was conducted at the Vrije Universiteit Amsterdam.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.poly.2013.12.024.
References
[1] A.D.F. Toy, J. Am. Chem. Soc. 70 (1948) 3882.
[2] C.R. Assis, A.G. Linhares, V.M. Oliveira, R.C. França, E.V. Carvalho, R.S. Bezerra,
L.B. De Carvalho Jr, Sci. Total Environ. 441 (2012) 141.
[3] A.S.V. Burgen, C.A. Keele, D. Slome, J. Pharmacol. Exp. Ther. 96 (1949) 396.
[4] Y. Watanabe, H. Nakahira, M. Bunya, S. Ozaki, Tetrahedron Lett. 28 (1987)
4179.
[5] J.F. Marecek, G.D. Prestwich, Tetrahedron Lett. 30 (1989) 5401.
[6] S.J. deSolms, J.P. Vacca, J.R. Huff, Tetrahedron Lett. 28 (1987) 4503.
[7] P.M. Chouinard, P.A. Bartlett, J. Org. Chem. 51 (1986) 75.
[8] H.Z. Schmidbaur, Z. Anorg. Allg. Chem. 326 (1964) 272.
[9] V.P. Mileshkevich, A.V. Karlin, Zh. Obshch. Khim. 40 (1970) 2573.
[10] K. Yamamoto, H. Watanabe, Chem. Lett. (1982) 1225.
[11] M.D. Mizhiritskii, V.O. Reikhsfel’d, Zh. Obshch. Khim. 55 (1985) 1883.
[12] T.P. Mawhinney, J. Chromatogr. 257 (1983) 37.
[13] H. Grunze, E. Thilo, Angew. Chem. 70 (1958) 73.
[14] H. Grunze, Chem. Ber. 92 (1959) 850.
4. Conclusions
[15] É.E. Nifant’ev, M.A. Kharshan, S.A. Lysenko, Zh. Obshch. Khim. 63 (1993) 776.
[16] T. Hiyama, M. Obayashi, Tetrahedron Lett. 24 (1983) 395.
[17] R.O. Sauer, J. Am. Chem. Soc. 66 (1944) 1707.
[18] K. Issleib, A. Balszuweit, A.-J. Richter, W. Tonk, Z. Chem. 23 (1983) 434.
[19] M. Schmidt, H. Schmidbaur, A. Binger, Chem. Ber. 93 (1960) 872.
[20] Z. Chen, L. Jiang, W. Su, Z. Xu, J. Chem. Soc. Pakistan 34 (2012) 1003.
In conclusion, we have developed the first efficient method for
the facile preparation of bulk amounts of tetrakis(trialkylsilyl)
diphosphate esters in large-scale and excellent yields. The silyl
diphosphate esters are amenable to both partial and total desilyla-