Full Papers
doi.org/10.1002/ejoc.202100067
complexes with alkali metal cations thereby releasing À OH
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anions. A similar activation of alkali metal hydroxides takes
place under phase-transfer conditions, when poorly solvated
À OH ions are transferred by bulky ammonium cations from the
aqueous to the organic phase. In all these cases, the pKa values
of these systems lie within 20–30 logarithmic units that
correspond to the superbasicity level.[36]
Scheme 2. Phosphonylation of alkyl bromides with red phosphorus in
multiphase systems under hybrid (micellar/phase transfer/superbase) catal-
ysis.
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During the above-integrated redox process (Scheme 1),
along with two ultimately reduced and oxidized phosphorus-
containing species (P3À , P(OH)3), other anions with phosphorus
atoms in a lower reduced state such as P2À OH, P1À (OH)2 are
formed. These intermediate anions can be intercepted by an
appropriate electrophile (organic halides, acetylenes, alkenes)
to furnish (depending on the reaction conditions and electro-
phile nature) tertiary phosphines, secondary and tertiary
phosphine oxides, and phosphinic acids (for the references see
the reviews[35f,g,37]). Recently, a simple and straightforward syn-
thesis of triarylphosphines (including Ph3P) from red
phosphorus and ArF in the superbasic KOH/NMP system has
been reported.[38] However, as yet the less accessible class of
organophosphorus compounds from those obtained by the
above elemental phosphorus-based approach remains alkyl-H-
phosphinic acids (7–38% yields),[39] while long-chain n-alkyl-
phosphonic acids, which are much more practically valuable,
have not been synthesized by this method at all. The synthesis
of alkyl-H-phosphinic acids was implemented by the phosphi-
nylation of alkyl bromides (C4-C8) under phase-transfer con-
ditions in the system elemental phosphorus (both red and
white)/KOH/H2O/PhMe/[Et3N+Bn]ClÀ (TEBAC as a catalyst). This
shows that the common phase transfer catalysis is not efficient
and selective enough to overcome this synthetic challenge.
Therefore we turn our attention to micellar catalysis, which now
gains strength in diverse fields of organic chemistry.[40] Among
the frequently employed micellar catalysts is cetyltrimeth-
ylammonium bromide (CTAB), which is a two-phase system,
simultaneously can play a role of phase transfer catalyst. This is
why, in this work we have used CTAB as a micellar/phase
transfer catalyst to facilitate the reaction between red
phosphorus and alkyl bromides in the multiphase system,
consisting of saturated (~50%) aq. KOH solution, red
phosphorus, and toluene.
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Depending on the catalyst nature the phosphonylation
proceeds under either hybrid phase transfer/superbase or
micellar/phase transfer/superbase catalysis. Finally, the reaction
mixture has been neutralized and simultaneously oxidized with
aq. HNO3 to release the target alkylphosphonic acids 2a–k.
To find out optimal reaction conditions we have chosen the
phosphonylation of n-octyl bromide as a reference reaction.
The main purpose of this experiment was to screen various
catalysts for their activity relative to that of CTAB. The other
variable reaction parameters were the following ones: the ratio
of the equivalents of n-OctBr:P:KOH, catalyst concentration,
duration of the reaction, temperature, and feeding time of n-
octyl bromide.
The constant reaction parameters were the loading of
phosphorus (0.1 g-atom, 3.1 g) and KOH·0.5H2O (20 g), as well
as volumes of H2O and toluene (13 and 60 mL, correspond-
ingly). The selective representative results of these experiments
are collected in Table 1. The preliminary experiments showed
that the yield of n-octylphosphonic acid and the conversion of
n-OctBr most strongly depended on the catalyst nature,
temperature, and the n-OctBr feeding time, on these very
reaction parameters the focus was made in the table, while
other reaction conditions were placed in the footnotes. The
preliminary experiments showed that the yield of n-octylphos-
phonic acid and the conversion of n-OctBr most strongly
depended on the catalyst nature, temperature, and the n-OctBr
feeding time. On these very reaction parameters the focus was
made in the table, while other reaction conditions were placed
in the footnotes to Table 1.
As seen from Table 1, the most active catalyst of the
phosphonylation studied proved to be CTAB, i.e. a typical
micelle-forming agent, providing the highest yield (91%) of n-
octylphosphonic acid, when the catalyst was used in 10 mol%
concentration (entry 1). However, in this case, the isolation of
the target product was complicated by excessive foam
formation as well as poor and time-consuming separation of
the layers due to superior surfactant properties of CTAB.
Consequently, here and in further experiments, we preferred to
stay with 5 mol% of CTAB securing 70% yield of phosphonic
acid 2e and a convenient workup of the reaction mixture.
Notably, that the yield of phosphonic acid 2e depended on the
AlkBr feeding time (cf. entries 2, 4 and 7, 8, Table 1), being lower
when n-OctBr was added more quickly (40 min vs 2 h and 1 h vs
2–4 h). The optimal feeding time was found to be 2 h. It follows
that the transfer of polyphosphide anions from aqueous to
organic phase should be approximately as fast as n-OctBr
feeding rate. If the latter is faster, then the side reactions with
Indeed, this hybrid micellar/phase transfer/superbase catal-
ysis in combination with in situ neutralization/oxidation of the
intermediate potassium phosphinates has allowed us to devel-
op a selective and efficient synthesis of alkylphosphonic acids.
Results and Discussion
The synthesis of alkylphosphonic acids by straightforward
phosphonylation of alkyl bromides 1a–k with red phosphorus
(Scheme 2) has been studied, as mentioned above, in multi-
phase systems comprising saturated (50%) aq. KOH and toluene
(two liquid phases), powdered red phosphorus (Pn) and micellar
aggregates (solid phases) and a phase transfer catalyst (mostly
quaternary ammonium salts as well as a crown ether).
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