Reinvestigation of the reaction between sodium diethyl phosphite and diethyl phosphorochloridate. Evidence for a SET process in the formation of a direct P(IV)-P(IV) bond

Article abstract of DOI:10.1016/S0040-4039(02)01916-0

Alkali metal salts of diethyl phosphites act as nucleophiles or electron donors in reactions with diethyl phosphorochloridate. Evidence is provided that formation of the direct P(IV)-P(IV) bond proceeds via a single electron transfer process (SET) from phosphite anion to phosphorochloridate.

Full text of DOI:10.1016/S0040-4039(02)01916-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7875–7879
Reinvestigation of the reaction between sodium diethyl phosphite
and diethyl phosphorochloridate. Evidence for a SET process in
the formation of a direct P(IV)ꢀP(IV) bond†
Ryszard W. Kinas, Andrzej Okruszek* and Wojciech J. Stec
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences,
Sienkiewicza 112, 90-363 Ło´dz´, Poland
Received 11 June 2002; revised 30 August 2002; accepted 6 September 2002
Abstract—Alkali metal salts of diethyl phosphites act as nucleophiles or electron donors in reactions with diethyl phosphorochlo-
ridate. Evidence is provided that formation of the direct P(IV)ꢀP(IV) bond proceeds via a single electron transfer process (SET)
from phosphite anion to phosphorochloridate. © 2002 Elsevier Science Ltd. All rights reserved.
Base-activated reactions of dialkyl phosphites with
dialkyl phosphorochloridates show great variation in
product formation depending on the nature of base
(sodium salt or amine promoted condensation), solvent
and other parameters.1–3 Tetraalkyl hypophosphates
were found to be formed in moderate yields when one
molar equivalent of dialkyl phosphorochloridate was
added dropwise into benzene solution/suspension of 1.5
molar equivalent of sodium dialkyl phosphite. As the
side products accompanying the formation of tetraalkyl
hypophosphate, some organophosphorus anhydrides,
including tetraalkyl pyrophosphite, tetraalkyl phospho-
rous–phosphoric anhydride, and tetraalkyl pyrophos-
phate, were reported to be present in a fraction of the
reaction mixture isolated by distillation in vacuo.1,3 The
reaction between dialkyl phosphite and dialkyl phos-
phorochloridate performed in the presence of tertiary
amines, afforded the mixture of aforementioned anhy-
drides, with no formation of hypophosphate.4 Taking
advantage of the possibilities offered by 31P NMR
spectroscopy for the qualitative and quantitative con-
trol of the reaction progress, the reaction between
sodium diethyl phosphite 1 and diethyl phosphorochlo-
ridate 2 was reinvestigated.5 The relative intensities of
31P NMR signals of phosphorus containing compounds
formed in the reaction between 1 and 2 (added in a
portionwise manner) are shown in Fig. 1.
After addition of ca. 30% of molar equivalent of 2, 31P
NMR analysis revealed the presence of tetraethyl
pyrophosphite 4, diethyl phosphate 7 and unreacted
sodium diethyl phosphite 1 in the ratio 20:32:35, respec-
tively. This observation can be rationalized by assum-
ing that phosphorochloridate
2
was subject to
nucleophilic attack by ambident diethyl phosphite
oxyanion 1 with a formation of pentacoordinate inter-
mediate 8a, with attacking phosphite residue and one of
ethoxy groups in apical positions. This intermediate can
Figure 1. The course of products formation in the reaction of
1 with 2: -ꢀ- tetraethyl hypophosphate (3); -ꢁ- sodium
diethyl phosphite (1); -ꢂ- diethyl phosphate (7); -ꢃ- tetra-
ethyl pyrophosphite (4); -"- tetraethyl phosphorous–phos-
* Corresponding author. Tel.: (+48 42) 681 69 70; fax: (+48 42) 681 54
83; e-mail: okruszek@bio.cbmm.lodz.pl
† This paper is dedicated to Professor Andrzej Zwierzak on the
occasion of his 70th birthday.
phoric anhydride (5);
tetraethyl pyrophosphate (6).
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01916-0

7876
R. W. Kinas et al. / Tetrahedron Letters 43 (2002) 7875–7879
Scheme 1.
undergo Berry Pseudorotation (BPR) to give isomeric
bypyramide 8b, possessing chlorine atom, a potential
leaving group, in apical position. Its collapse, which can
proceed by departure of chloride anion and its instanta-
neous (inside a solvent cage) attack at the trivalent
phosphorus, leads to the diethyl phosphate 7 and
diethyl phosphorochloridite 9.4 The latter compound
could not be observed in 31P NMR spectrum because of
its instantaneous reaction with an excess of 1 giving rise
to the formation of tetraethyl pyrophosphite 4 (Scheme
1). Further addition of 2 caused a decrease of concen-
tration of the anhydride 4 and initiated the formation
of tetraethyl hypophosphate 3. The content of 3
reached its highest value (46% of relative intensity) after
addition of ca. 60% of molar equivalent of 2. In addi-
tion, some amounts of tetraethyl pyrophosphate 6 and
tetraethyl phosphorous–phosphoric anhydride 5 were
also identified in the reaction mixture. The formation of
these two products can be rationalized in terms of
subsequent reactions of 7 with 2, 4 or 9.4
ferred from the anion 1 to 2, giving rise to the forma-
tion of the radical–radical anion pair 10/11, a typical
electron donor–electron acceptor complex (EDA). The
formation of tetraethyl hypophosphate 3 may result
either from the coupling of the radical 10 with radical
anion 11 within EDA complex in a solvent cage
(Scheme 2, path a), or from free radical chain process
outside the solvent cage, with the participation of radi-
cal 10 and hypophosphate radical anion 12 (path b).
The participation of free radicals accompanying reac-
tions of dialkyl phosphites and their salts has been well
documented in the literature. Free radicals were
detected in reaction mixtures during photochemical
decomposition of dialkyl (trichloromethyl)phosphon-
ates,6 electrochemical oxidation of dialkyl phosphites7
and photolysis of acetone in the presence of dialkyl
phosphites.8 The functioning of dialkyl phosphite
anions as single electron donors was observed in their
reactions with alkyl halides or aryl halides, otherwise
For the formation of the direct P(IV)ꢀP(IV) bond in the
reaction of 1 with 2, two feasible pathways can be
considered. One route, as was assumed previously,1,3
involves an ionic process of nucleophilic substitution of
the SN2P type at the phosphorus atom of phospho-
rochloridate 2, with the dialkyl phosphite anion acting
as an ambident nucleophile. Inspection of Fig. 1 leads
to a conclusion that the process of direct P(IV)ꢀP(IV)
bond formation leading to 3 is initiated after partial
(ca. 30%) addition of the phosphorochloridate 2. An
alternative to the aforementioned nucleophilic substitu-
tion reaction leading to the hypophosphate 3, so far not
considered, is a single electron transfer process (SET). It
is now assumed that tetraethyl pyrophosphite 4, formed
at the first stage of the process, interacts with 1 by
binding the sodium cation, thus causing the initiation
of the SET pathway. The phosphite anion and phos-
phorochloridate 2 form an electron donor–electron
acceptor complex, in which a single electron is trans-
Scheme 2.

R. W. Kinas et al. / Tetrahedron Letters 43 (2002) 7875–7879
7877
Figure 2. 31P NMR spectrum of (a) hypophosphate 3 and (b) pyrophosphate 6 derived from the reaction of sodium diethyl
18O-phosphite 1 with diethyl phosphorochloridate 2. Minor resonances at 8.304 and 8.261 (spectrum a) correspond to labeled
diethyl phosphite formed by partial hydrolysis of labeled hypophosphate 3 during its isolation.
known to be very efficient electron acceptors.9–11
Dialkyl phosphorochloridate radical anion 11, pro-
posed as the key component of reactive EDA complex
10/11 leading to hypophosphate 3 (Scheme 2), was
recently suggested as an intermediate in the reductive
cleavage of halogen–phosphorus bond.12
gen-labeled pyrophosphate. The lines at −11.403 and
−11.429 ppm can be assigned to compounds containing
18O-isotope in the bridging site, and in both bridging
and non-bridging positions of the labeled pyrophos-
phate 6, respectively. The isotopomer containing 18O in
non-bridging position shows an extreme AB system,15,16
with weak outer lines at −11.330 and −11.484 ppm and
resolved inner lines at −11.403 and −11.413 ppm (the
downfield line overlaps with the resonance of the sym-
In order to provide evidence for the reaction mecha-
nism outlined in Scheme 2, involving the intermediacy
of radical 10 and radical anion 11, condensation experi-
ments were carried out with 18O-labeled 1, or in the
presence of radical scavengers. The reaction of 18O-
labeled 1 with 2, performed by addition of 0.66 mol.
equiv. of 2 into a suspension of 1 mol. equiv. of 1 in
toluene yielded, after chromatographic separation from
unreacted 1, a mixture of 3 and 6.13 Hypophosphate 3
showed in the proton-decoupled 31P NMR spectrum
(Fig. 2a) two distinguishable signals at l 8.047 (42%)
and l 8.025 (58%). The presence of 18O isotope induced
a small upfield shift (Dl 0.022 ppm) in the 31P NMR
frequency of hypophosphate 3, the magnitude of which
is characteristic to a Pꢁ18O double bond.14 Isotope
enrichment of the hypophosphate 3, as determined by
31P NMR (58%) and GC MS (55%) was, within experi-
mental error, the same as isotope enrichment of the
substrate 1 (56%, GC MS). No resonance with Dl ca.
0.044 ppm and no M+4 ion, corresponding to 18O-dou-
ble labeled hypophosphate 3, the hypothetical product
of recombination of two 18O-phosphite radicals 10, was
observed. As anticipated, the hypophosphate 3 was
built up from fragments of one molecule of the phos-
phorochloridate 2 and one molecule of the 18O-phos-
phite 1. Another important conclusion can be drawn
from 31P NMR spectrum of the pyrophosphate 6
obtained from 18O-labeled 113 (Fig. 2b) which showed a
resonance at −11.388 ppm due to the unlabeled 6, and
three upfield shifted resonances corresponding to oxy-
2
metrically labeled 6, JPP=14.6 Hz). The observed Dl
values 0.015, 0.025 and 0.041 ppm are in reasonable
agreement with previously described magnitude of
upfield shift induced by 18O isotope in single (Pꢀ18O)
and double (Pꢁ18O) bond. The calculated total isotope
enrichment of the pyrophosphate 6 (53%) was found to
be only slightly lower than that of phosphite 1 (56%),
indicating that one of the oxygen atoms of pyrophos-
phate molecule originates from starting phosphite.
Since the most probable source of pyrophosphate 6 is
the side reaction of 2 (unlabeled) with phosphate 7, the
presence of oxygen label in 6 confirms the postulated
mechanism of the first step of process, in which oxygen
atom migrates from 1 to 7 with the participation of
pentacoordinate intermediate 8 (Scheme 1).
The results of further experiments, involving the reac-
tion of diethyl phosphorochloridate 2 with sodium
diethyl phosphite 1 and its analogs containing other
cations (Li+, K+), under various experimental condi-
tions, are listed in Table 1. Using free radical scav-
enger–galvinoxyl (Table 1, entry 2) or radical anion
scavenger–p-dinitrobenzene (PDB, Table 1, entry 3)
added to the reaction mixture, a marked lowering of
the yield of the hypophosphate 3 was observed, from
74% (no scavenger added) to 44 or 28%, respectively.
Partial inhibition by radical scavengers confirms our
assumption that the formation of hypophosphate 3 in

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R. W. Kinas et al. / Tetrahedron Letters 43 (2002) 7875–7879
Table 1. Reactions of alkali metal salts of diethyl phosphite 1 with diethyl phosphorochloridate 2
Entry
Counter-ion of 1
Solvent and molar concentration of 1
Additives or reaction conditions
Yield of 3a (%)
1
2
3
4
5
6
7
8
Na+ (c)
Na+ (c)
Na+ (c)
Na+ (c)
Li+ (d)
Na+ (c)
K+ (e)
Toluene, 1.2
Toluene, 1.2
Toluene, 1.2
Toluene, 1.2
THF, 2.4
THF, 2.4
THF, 2.4
Acetonitrile, 1.2
None
74
44
28
73
0
2
17
29
Galvinoxylb
PDBb
Reaction in the dark
None
None
None
None
Na+ (f)
a Yields were determined by integration of 31P NMR spectra and calculated as a percentage of conversion of 2 to 3.
b 0.132 molar equiv. of galvinoxyl or PDB was added into suspension of 1.
Elemental sodium(c), butyllithium(d), potassium tert-butoxide(e) and sodium hydride(f) were used for diethyl phosphite salt generation prior to its
reaction with 2.
the reaction of sodium diethyl phosphite 1 with diethyl
phosphorochloridate 2 could be an example of a single
electron transfer process. The electron transfer nature
of this reaction should then be a function of the oxy-
genation potential of diethyl phosphite salt and the
solvent. Indeed, while sodium and potassium phos-
phites 1 gave observable yields of tetraethyl hypophos-
phate 3 when the reaction was performed in THF
solution (Table 1, entries 6 and 7), under identical
(Scheme 2, path a) to form the final product—tetra-
ethyl hypophosphate 3.
Acknowledgements
Studies described in this report were financially assisted
by the State Committee for Scientific Research (KBN).
experimental conditions formation of
3 was not
observed with lithium salt (entry 5), otherwise known
to undergo electrochemical oxidation at higher anodic
potential than sodium salt.17 No influence on the yield
of hypophosphate formation was observed when reac-
tion was carried out in the dark in toluene solution
(entry 4).
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