Microwave michaelis-becker synthesis of diethyl phosphonates, tetraethyl diphosphonates, and their total or partial dealkylation

Article abstract of DOI:10.1002/hc.20561

Diethyl phosphonates and tetraethyl alkyldiphosphonates were efficiently and rapidly prepared via the Michaelis-Becker reaction, under microwave irradiation. These compounds were then hydrolyzed to phosphonic and diphosphonic acids or selectively monodealkylated to give monoesters of phosphonic acids and symmetrical diethyl esters of diphosphonic acids. These reactions were also achieved rapidly in satisfactory yields with microwave methodology. This methodology was applied with success to the functionalization of a polymer resin.

Full text of DOI:10.1002/hc.20561

Heteroatom Chemistry
Volume 20, Number 6, 2009
M
icrowave Michaelis–Becker Synthesis
of Diethyl Phosphonates, Tetraethyl
Diphosphonates, and Their Total
or Partial Dealkylation
1,2
1
2
Dalila Meziane, Julie Hardouin, Abdelhamid Elias,
1
1
Erwann Gu e´ nin, and Marc Lecouvey
1
Equipe Chimie Bioorganique et Bionanomat e´ riaux (C2B) Laboratoire CSPBAT. FRE 3043 CNRS
Universit e´ Paris 13 74 Rue Marcel Cachin, F-93017 Bobigny, France
2
◦
D e´ partement de Chimie, Facult e´ des Sciences Universit e´ Mouloud Mammeri, B.P N 17 RP,
5000 Tizi Ouzou, Alg e´ rie
1
Received 14 April 2009; revised 16 June 2009
pesticidal, and enzyme inhibitory properties [1–5].
Moreover, molecules containing phosphonate moi-
ety have elicited many interest for their chelating
properties with applications in imaging, catalysis,
and ion exchange [6,7]. Finally, phosphonate con-
taining polymers have been widely studied as fire re-
tardant, promoters for paints and adhesives, as ion
exchanger, or in extraction systems [8–13]. Among
the methods described for the formation of car-
bon phosphorus bound Michaelis–Arbuzov [14] and
Michaelis–Becker reactions (MA and MB, respec-
tively) represent the easiest and more used syn-
thetic pathways toward the obtaining of phospho-
nate. Although very efficient methods for reactive
and simple substrates, these reactions suffer from
some drawbacks (such as length of reaction time,
need of high reaction temperatures, and by-products
formation) and are sometimes less efficient for un-
reactive substrates such as fatty alkyl halides [15].
While microwave dielectric heating had been widely
exploited in several organic chemistry areas to accel-
erate and improve reactions yields [16,17], it has not
been often applied to phosphorus chemistry. Less
than 15 studies were conducted [18–21]. To the best
of our knowledge, few studies dealt with the MA re-
action [22,23] and none with MB, though these two
reactions using or evolving through ionic species are
particularly fitted for microwave applications.
ABSTRACT: Diethyl phosphonates and tetraethyl
alkyldiphosphonates were efficiently and rapidly pre-
pared via the Michaelis–Becker reaction, under mi-
crowave irradiation. These compounds were then
hydrolyzed to phosphonic and diphosphonic acids
or selectively monodealkylated to give monoesters
of phosphonic acids and symmetrical diethyl es-
ters of diphosphonic acids. These reactions were
also achieved rapidly in satisfactory yields with mi-
crowave methodology. This methodology was applied
with success to the functionalization of a polymer
resin. ꢀC 2009 Wiley Periodicals, Inc. Heteroatom Chem
2
0:369–377, 2009; Published online in Wiley InterScience
(
www.interscience.wiley.com). DOI 10.1002/hc.20561
INTRODUCTION
Among organophosphorus compounds, phospho-
nic acids (or phosphonate) have generated consid-
erable synthetic interest for their numerous uses.
Phosphonic analogues of naturally occurring phos-
phates or carboxylic acids have attracted atten-
tion due to their antibacterial, antiviral, antibiotic,
Correspondence to: Erwann Gu e´ nin; e-mail: guenin@
univ-paris13.fr.
ꢀ
c 2009 Wiley Periodicals, Inc.
369

370 Meziane et al.
Herein, we propose to study the use of mi-
TABLE 1 Reaction Conditions for the Obtaining of Com-
pound 1a and 1b with MA or MB Methodology
crowave technology for MB reactions especially with
unreactive fatty halides or secondary alkylhalides
and we showed the interest of such methodology for
the diphosphonic compounds synthesis. We, more-
over, studied several microwave-assisted solutions
for the cleavage of alkyl phosphonates to obtain
phosphonic acids or partial esters. We finally ap-
plied this methodology to the functionalization of
a polymer resin.
Method
Oil Bath Heating
Microwave Irradiation
Reaction
type
Compound
Time
MA
MA
MB
MA
MA
MB
1a
1b
1b
1a
1b
1b
20 h 04 h 24 h 50 min 40 min 03 min
X
T
0.08 0.66 0.20
0.20
112
150
0.62
160
250
0.98
85
120
a
a
a
112 160
85
–
Power (W)
–
–
aProgrammed Tmax
.
RESULTS AND DISCUSSION
We first wanted to apply the microwave tech-
nology to relatively unreactive substrates such as
prove yields. The optimal ratio of reactant used was
P(OR)
ogy, and NaP(OEt)
methodology. The conversion ratio of dodecylbro-
3
/RBr = 2 in the case of the MA methodol-
1-bromododecane on which studies with MA reac-
ꢁ
2
/R Br = 1.1 in the case of the MB
tions have already been conducted using conven-
tional heating with trimethyl or triethyl phosphite
mide to the desired dialkyl dodecylphosphonate (1a
[15]. We performed the reaction using the MA or MB
1
or 1b) was measured by integrating H NMR signals
methodology in the same conditions (such as same
vessel, same quantities, and same stoichiometry) us-
ing whether classical oil bath heating or microwave
irradiation (Scheme 1).
corresponding to the two compounds. As described
by Pelaprat et al. [15], we integrated the signal cor-
responding to the proton of terminating methyl on
the alkyl chain at 0.86 ppm (noted hCH3 ) and the sig-
nal corresponding to the methylene proton bearing
Using MA methodology, reactions were con-
ducted without solvent, and in both heating modes
the reaction media was preheated prior to the alkyl
halide addition to avoid formation of methyl or
ethylphosphonate. With the MB methodology, we
first carried out the reaction in the presence of a
solvent, e.g., acetonitrile. The 1-bromododecane was
added to a suspension of sodium diethylphosphite in
acetonitrile at room temperature and then heated in
an oil bath or using microwave. For both method-
ologies, various experimental conditions were stud-
ied: varying temperature, reaction time, irradiation
power, and ratio of reagents. The optimal conditions
are presented in Table 1. One must note that for
each reaction an increase in the reaction time, ra-
tio of reactants, or of irradiation power did not im-
the bromine at 3.4 ppm (noted hCH Br). The following
2
relation gave the conversion ratio noted X (Eq. (1)):
ꢀ
ꢁꢂ
h
CH Br
2
2
ꢀ
ꢁꢂ = 1 − X
(1)
h
CH3
3
Using MA methodology, we found that as
reported by Villemin et al. [22], microwave ir-
radiation decreases the reaction time, but for
1-bromododecane no considerable enhancement in
yield was noted. The reaction still did not go to
completion whatever the conditions tried; the reac-
tion with trimethylphosphite remaining more dif-
ficult than with diethylphosphite. With microwave
dielectric heating, only traces of methyl or ethyl
phosphonate were observed; using oil bath, forma-
tion of ethylphosphonate was observed and methyl
phosphonate was the main product. Finally, when
using triethylphosphite compound, 1b was sepa-
rated from the unreacted 1-bromododecane on sil-
ica gel chromatography and isolated with 55% yield.
Using MB methodology the results were remarkable.
Not only the time reaction was drastically decreased,
but also the conversion ratio was greatly improved.
Moreover, olefin by-product was never observed.
Nevertheless, the irradiation power must be kept un-
der 150 W because temperature could increase very
quickly (within few seconds). One must note that
the reaction could even be done without any sol-
vent with the same results. Using the best condition,
the diethyldodecylphosphonate 1b was obtained in
Michaelis Arbusov reaction
OR
OR
O
P
C12H25Br
OR
OR
RO
P
C12H25
R = CH3 : 1a
R = C H5 : 1b
2
Michaelis Becker reaction
O
O
P
OEt
Na
OEt
R'X
OEt
OEt
HO
P
Na:P
R'
OEt
(X = Br, Cl)
OEt
R' = C12
H
3 2
25
: 1b
: 2
R' = (CH ) CH
R' = (C H )(CH )CH : 3
7
15
3
SCHEME 1
Heteroatom Chemistry DOI 10.1002/hc

Microwave Michaelis–Becker Synthesis of Diethyl Phosphonates, Tetraethyl Diphosphonates, and Their Total or Partial Dealkylation 371
9
5% yield after purification by silica gel chromatog-
raphy. We then tried to reproduce this result with
-chlorododecane. Chloroalkanes are known to be
O
O
P
O
P
OEt
OEt
EtO
EtO
OEt
OEt
Br
Br
n
+
Na: P
n
1
6
– 8
less reactive in MA or MB reactions than bromoalka-
nes. Applying MB microwave methodology, the cor-
responding phosphonate 1b was obtained with 35%
yield (after purification on silica gel chromatogra-
phy) within 15 min. This was an appreciable yield,
because it was higher than those obtained with
SCHEME 3
tention of configuration due to the apical attack. This
phenomenon exists for nucleophile able of expand-
ing their valence shells such as phosphorus species
1
-bromododecane within 24 h under conventional
heating.
In a second step, we tried to evaluate whether
[26].
In a third part of this work, we wanted to evalu-
the MB reaction using microwave methodology was
possible with secondary halogenoalkane. We choose
ate this methodology of the synthesis of diphosphos-
phonate. Diphosphonic acids (and diphosphonates)
have numerous applications ranging from the sim-
plest one, tetraethylmethylene diphosphonate that
is an useful intermediate for the synthesis of bioac-
tive compound, to longer one (n = 3–12) which could
have several applications, such as metals extraction,
obtaining of porous materials, and so on [27–32].
The preparation of these compounds has already
been reported for short alkyl chains using the Arbu-
zov reaction, but appreciable yields are needed for
the use of triethylphosphite excess and long-time re-
actions [29,33]. We therefore applied the conditions
developed for the MB reaction from bromododecane
to several dihalogeno-alkanes (Scheme 3).
2-bromopropane and 2-bromononane as substrates.
The reaction was carried out using the following
optimized conditions: 150 W, 40 min. The dialkyl
phosphonates 2 and 3 were obtained with 30% yield
after purification on silica gel column chromatogra-
phy. As the reaction did not go to completion, we
1
checked by H NMR in the reaction media that for-
mation of nonene by-product did not occurred us-
ing bromononane. Only unreacted starting material
remained. We furthermore tried to study the mech-
anism of our reaction with secondary substrates. In
the literature, there have been several kinetic inves-
tigations of the Arbuzov reaction [14], but there are
only few reports on the Michaelis–Becker reaction
mechanism [24]. It seems well established to un-
dergo through an SN2 mechanism and was proved
in some conditions [25]. Using microwave, the influ-
ence of solvent on the reaction yield was consistent
with the SN2 mechanism. Use of DMF slightly in-
creased the speed of the reaction (yield of phospho-
nate 2 was increased for the same reaction time),
whereas use of THF decreased it (data not shown).
To further prove the SN2 mechanism, we carried
out reactions with both enantiomerically pure R and
S sec-butyl methylsulfonate and we measured spe-
cific optical rotation for the obtained phosphonate
products (Scheme 2). Unfortunately, racemization
occurred. Nevertheless the reaction did not evolved
through an SN1 type mechanism as using iso-butyl
methylsulfonate no rearrangement product was ob-
served. So this result could be explained by the possi-
bility of attack on the carbon–halogen bond with re-
The reactions were done in the same conditions
(such as same vessel, same quantities, and same sto-
ichiometry) using the conventional method: oil bath
heating in refluxing acetonitrile or using microwave
irradiation at 100 W.
For compounds 6–8, we showed that at least 2 h
was required by thermal heating for almost com-
pletion of reactions in contrast with microwave di-
electric heating where only 2–3 min was sufficient
(see Table 2). The diphosphonates were then pu-
rified by silica gel column chromatography. The
most impressive result was the synthesis of tetraethyl
methylenediphosphonate 9 from sodium diethyl
phosphite and dichloromethane (Scheme 4): The
previously described method [34] implies at least a
TABLE 2 Comparison of the MB Conditions for Obtaining of
Compounds 6–8
Oil Bath Heating Microwave Irradiation
C
2
H
5
C
2
H
5
O
O
C H
O
P
2
5
ClSO
2
Me
NaPO(OEt)2
OEt
OEt
CH OH
CH O
S
CH
3
CH
H C
Time
(h)
Yield
(%)
Time
(min)
Yield
(%)
NEt
3
H
3
C
H
3
C
Compound
X
n
6
3
4
5
R
S
R
S
[
[
]
]
neat= –10.6
neat= +10.9
[
[
]
]
neat= –14.6
neat= +14.8
6
7
8
Br
Br 10
Br 12
1.5
2
2
85
90
95
2
3
3
96
90
95
[ ]neat = 0
SCHEME 2
Heteroatom Chemistry DOI 10.1002/hc

372 Meziane et al.
O
OEt
O
of a new peak around 26 ppm corresponding to
the silylated intermediate; the end of the reaction
corresponds to the total disappearance of the ini-
tial peak around 32 ppm. After a methanolysis step,
conversions of alkyl phosphonates into phosphonic
acids were found to be quantitative. Reactions were
completed within 2 min using bromotrimethylsilane
or the mixture of trimethylsilylchloride and sodium
iodide. But in the latter case, the purification was
sometimes tedious that explains why we had lower
products yields.
OEt
OEt
Na: P
O
P
Na: P
O
P
O
P
OEt
EtO
EtO
EtO
EtO
OEt
OEt
CH
2
Cl
2
Cl
(
MW, 20 min)
(MW, 10 min)
not isolated
9
SCHEME 4
1
-month stirring time to obtain a 50% yield, whereas
using microwave the same results were achieved
within 30 min.
The reaction was carried out in two steps when
using microwave technology. A first equivalent of
sodium phosphite was irradiated for 20 min in
dichloromethane until no sodium phosphite re-
mained in the mixture and then, after evaporation of
the dichloromethane, a second equivalent of sodium
phosphite was added and irradiated for 10 min. The
tetraethyl methylenediphosphonate 9 was separated
from the diethyl chloromethylphosphite by distilla-
tion under reduced pressure and was obtained with
a yield of 50%.
Mineral acid hydrolysis of alkyl phosphonates
represents a more general pathway toward obtaining
phosphonic acid(s) [35]. We, therefore, tried to ap-
ply microwave irradiation to this reaction. Unfortu-
nately, although water is described as one of the best
solvent for microwave reaction, we have not been
able to conclude whether there was any sensible im-
provement in the reaction time. So we turned toward
the alternative mild methods employing silylating
agents [36,37]. It was already demonstrated that us-
ing trimethylsilylbromide the cleavage of phospho-
nates esters proceeds faster under microwave con-
ditions without compromising product yields [38].
We applied the described conditions to our mono-
or diphosphonates with success. We also decided to
evaluate the other silylating solution often used and
less expensive: the mixture of trimethylsilylchloride
and sodium iodide (Scheme 5) [37].
We, then, evaluated the microwave synthesis
of partial phosphonic esters of our phosphonate
and diphosphonate compounds. The obtaining of
monoalkyl esters of alkyl phosphonates could be
of great interest for several applications (biological
or extraction) [32,39–41]. Besides beneficial applica-
tion, use of monoalkyl alkylphosphonate in the iden-
tification of phosphorus chemical warfare agents is
noteworthy [42]. Apart from the use of thiolates
[43], sodium iodide is the usual reactant to mon-
odealkylate, a phosphonate, and could even be used
on diphosphonate to realize symmetric monodealky-
lation [44]. Reactions were performed in methanol
under microwave irradiation to give, after acidifica-
tion, ethyl dodecylphosphonic acid 14 and symmet-
rically substituted diethyl alkyldiphosphonic acids
15–17 (Scheme 6). Good yields in isolated products
(60%–75%) were obtained in less than 30 min reac-
tion, whereas on conventional heating similar reac-
tion took several hours for the same results [44].
Finally, we applied this methodology to the
functionalization of a polymer resin. We choose a
®
NovaSyn TG bromo resin: a composite of low cross-
linked polystyrene and 3000–4000 MW polyethylene
glycol in which the ends of the PEG chains have
been bromofunctionalized (see Scheme 7). It was
treated by an excess of sodium diethylphosphonate
in acetonitrile under microwave irradiation (70 W,
4 min). The cleavage of the esters was achieved with
trimethylsilylbromide using microwave activation.
The functionalization was qualitatively assessed by
staining resin beads with phosphomolybdenic acid
The reaction was carried out in acetonitrile for
31
1
all our compounds and followed by P{ H} NMR.
The P{ H} NMR spectrum showed the apparition
31
1
O
P
O
P
EtO
EtO
HO
C12H25
C12H25
O
P
O
P
EtO
EtO
HO
HO
EtO
C12H25
C12H25
14
1) NaI
2) HCl
1
) BrSi(Me)
3
1
0
or ClSi(Me)3 / NaI
O
O
O
O
P
O
O
2) MeOH
O
O
P
EtO
EtO
OEt
P
HO
OH
EtO
EtO
OEt
P
HO
HO
OH
OH
P
P
P
P
n
OEt
EtO
n
OEt
n
OEt
n
11 – 13
15 – 17
SCHEME 5
SCHEME 6
Heteroatom Chemistry DOI 10.1002/hc

Microwave Michaelis–Becker Synthesis of Diethyl Phosphonates, Tetraethyl Diphosphonates, and Their Total or Partial Dealkylation 373
O
less otherwise noted. Trialkyl and dialkylphosphites
were distilled before use. All solvents were dis-
tilled before use. Dichloromethane and acetonitrile
OEt
OEt
NaP
OEt 1) BrSiMe
OEt
3
OH
OH
Br
P
P
O
O
2
) MeOH
were distilled from P
2
O . Methanol was distilled
5
18
®
from sodium. The NovaSyn TG bromo was bought
from Novabiochem (Merck-chemicals, Fontenay-
sous-bois, France). NMR spectra were recorded with
SCHEME 7
13
1
a VARIAN Unity Inova 500 MHz ( C: 125.9, H:
and was qualitatively calculated by conductometric
and acidic titration methods. Loading in phosphinic
acids functions was found to be equal to the loading
in brominated functions as provided by the supplier.
3
1
5
00.6 MHz, P: 200.7 MHz) or a VARIAN Gem-
13
1
31
ini 200 MHZ ( C: 50.3 MHz, H: 200 MHz, P:
0.9 MHz) spectrometer in CDCl or CD OD. Chemi-
cal shifts (δ) are given in ppm. The solvent peak was
8
3
3
1
13
used as a reference for H NMR and C NMR. The
CONCLUSION
values are, respectively, 7.26 and 77.2 ppm for CDCl ,
3
31
3
.31 and 49.0 ppm for CD OD. P spectra were
3
In conclusion, we propose herein an efficient and
rapid method enabling the synthesis of phospho-
nate or diphosphonate from various alkylhalides.
This method was based on development of the
Michaelis–Becker reaction under microwave irradi-
ation. We showed that phosphonates or diphospho-
nates were obtained with better yields and in less
time than when using classical heating technology.
No olefin products were produced during these reac-
tions. Moreover, this methodology permits the use of
less reactive fatty halides or secondary halides sub-
strates. The reaction mechanism under microwave
irradiation was studied with secondary substrates.
Evidences of the SN2-type mechanism were found,
but racemization occurred probably due to an apical
attack. Microwave technology was further used to
hydrolyze phosphonic esters. As already described in
the literature, use of bromotrimethylsilane followed
by methanolysis enables the complete, rapid, and ef-
ficient hydrolysis of phosphonic esters. We showed
that the inexpensive mixture of chlorotrimethylsi-
lane/sodium iodide could afford the same results.
Furthermore, we showed that under microwave irra-
diation sodium iodide partially hydrolyzed phospho-
nic ester functions. Finally, we successfully applied
this methodology to functionalization of a polymer
resin.
recorded with phosphoric acid (85%) as external ref-
erence. The IR spectra were recorded using a Nico-
let FTIR 380 spectrometer. The mass spectra were
run on a MALDI–TOF mass spectrometer (Biflex IV,
Bruker Daltonique) with 2,5-dihydroxybenzoic acid
as matrix. Optical rotations were measured on a 314
Perkin–Elmer polarimeter. All melting points were
recorded using a Stuart SMP3 melting point appa-
ratus and are uncorrected.
General Procedure for the Conventional and the
Microwave Arbuzov Synthesis of Dialkyl
Dodecylphosphonates (1a–1b)
The trialkylphosphites (40 mmol) were first heated
◦
at approximately 100 C, then dodecylbromide was
added in an appropriate ratio. The mixture was
◦
◦
then heated at 160 C (triethyl phosphite) or 112 C
trimethyl phosphite) for 4–20 h. Using microwave,
(
the trialkylphosphites were irradiated until the tem-
◦
perature reached 100 C, dodecylbromide (20 mmol)
was added, and the mixture was irradiated again
for 40–50 min. All experiments were run under ar-
gon atmosphere. The evolution of the reaction was
31
monitored by P. The excess of trialkylphosphite
was evaporated under reduced pressure. The desired
phosphonate was separated from the unreacted bro-
mide by flash chromatography. The bromide was
eluted with hexane/ethyl acetate (90/10), then the
phosphonate was recovered with pure ethyl acetate.
EXPERIMENTAL
General
All experiments under microwave irradiations
were run in open vessel, using a CEM-Discover
monomode microwave apparatus. The irradiation
was done at a fixed power for 2–5 min irradia-
tion followed by return at room temperature. This
ensured no local heating especially with hetero-
geneous media such as with sodium phosphonate
and the polymer resin. All reagents were commer-
cial grade and were used without purification un-
General Procedure for the Mickaelis–Becker
Synthesis of Diethyl Phosphonates (1b, 2, 3)
and Tetraethyl Diphosphonates (6–8)
A solution of diethylphosphite (6.1 g, 44 mmol) in
acetonitrile (15 mL) was degassed with argon under
magnetic stirring for approximately 10 min. Metallic
sodium (1.1 g, 44 mmol) was added to the solution by
◦
small portions at 0 C. The solution was stirred until
Heteroatom Chemistry DOI 10.1002/hc

374 Meziane et al.
3
the sodium completely dissolved; this required only
few minutes. The alkyl bromide or dibromide (40 or
J
= 19.0 Hz CH CH-P), 1.20–1.35 (m, 16H,
H−P
3
3
CH CH CH (CH ) CH CH CHP and CH CH OP),
2
2
2
2
2
2
3
2
2
0 mmol) was then added. A reflux condenser was
1.44 (m, 2H, CH CHP), 1.75 (m, 1H, CHP), 4.09
2
13
1
then placed, and the setup was closed with a calcium
chloride tube. The reaction mixture was then irradi-
ated or heated according to the microwave or classic
(m, 4H, CH OP). C { H} NMR (CDCl , 125.9 MHz,
2
3
2
298 K): 13.2 (d,
(s, CH3 (CH ) CHP), 16.6 (d,
CH CH OP), 22.8 (s, CH CH (CH ) CHP), 27.6
J
C−P
= 5.8 Hz, CH CHP), 14.3
3
3
2
6
J
C−P
= 5.8 Hz,
5
method. The solvent was then evaporated, and H
2
O
3
3
2
3
2
2
(50 mL) and diethyl ether (150 mL) were added to the
(d,
J
= 13.6 Hz, CH CH CHP), 29.3–29.5 (s,
2
2 2 2 2 2
C−P
2
2
residue. The crude product was extracted, and the
organic layer was washed, respectively, with NaOH
CH CH CH (CH ) CH CH CHP), 30.0 (d,
J
C−P
=
3
2
1
3.9 Hz, CH CHP), 30.9 (d, J
2
C−P
= 140.3 Hz, CHP),
(
1 M) (2 × 50 mL), HCl (1 M) (2 × 50 mL), and water.
32.0 (s, CH CH CH (CH ) CH CH CHP), 61.6 (d,
3
2
2
2
2
2
2
2
The organic layer was dried over anhydrous MgSO
filtered, and evaporated.
4
,
J
= 5.8 Hz, CH OP).
C−P
2
In the case of compound (1b, 2, 3), the crude
yellow oils were purified by column chromatography
over a silica column using, first n-hexane gradually
enriched with ethyl acetate then the desired products
were recovered by methanol (5%) in ethyl acetate.
Synthesis of Diethyl Phosphonate (5). This com-
pound was prepared as described above using the
mesylate 4 instead of an alkyl bromide. Microwave:
3
1
1
20 min, 100 W: yield: 20% P { H} NMR (CDCl ,
3
1
80.9 MHz, 298 K): 35.5. H NMR (CDCl , 500 MHz,
3
3
2
98 K): 0.96 (t, 3H, JH−H = 7.3 Hz, CH
3
CH CHP),
2
3
3
Diethyldodecylphosphonate (1b). Classical heat-
1.14 (dd, 3H, J
= 7.3 Hz, J
= 11.7 Hz CH CH-
H−H
H−P
3
◦
3
ing: 4 h, 160 C, yield: 60% (the MA reaction); 24 h,
P), 1.29 (t, 6H, J
= 7.3 Hz CH CH OP), 1.65–
H−H
3
2
◦
8
4
1
5 C, yield: 20% (the MB reaction). Microwave:
1.85 (m, 2H, CH CH CHP), 4.07 (m, 4H, CH OP).
3
2
2
13
1
0 min, 250 W, yield 55% (the MA reaction); 03 min,
C { H}NMR (CDCl , 125.9 MHz, 298 K): 12.2 (d,
3
31
1
3
2
20 W, yield 95% (the MB reaction). P{ H} NMR
J
= 13.7 Hz, CH CH CHP), 12.8 (d,
J
C−P
3
=
2
C−P
3
2
1
2
(
CDCl
3
80.9 MHz, 298 K): 32.0. H NMR (CDCl
3
,
3.9 Hz, CH CHP), 16.7 (d, J
= 3.9 Hz, CH CH -
3
C−P
3
2
5
CH
CH
00 MHz, 298 K): 0.81 (t, 3H,
(CH P), 1.18–1.29 (m, 18H, CH
CH
P) 1.25 (t, 3H, JH−H = 7.0 Hz, CH
.66 (m, 2H, CH CH P), 1.75 (m, 2H, CH
J
H−H = 7.0 Hz,
OP), 23.2 (d,
J
C−P
= 3.9 Hz, CH CH CHP), 27.6
3 2
3
1
3
2
)
10CH
2
3
(CH
CH OP),
P), 4.01
, 125.9 MHz,
2
)
9
(d, J
C−P
= 13.6 Hz, CH CH CHP), 32.0 (d, J
2
2
2
C−P
=
3
2
2
3
2
140.6 Hz, CHP), 61.5 (d, J
C−P
= 7.8 Hz, CH OP).
2
1
2
1
2
2
3
1
(
m, 4H, CH
2
OP). C { H}NMR (CDCl
3
3
Tetraethyl Hexane-1, 6–diyldiphosphonate (6).
◦
298 K): 14.3 (s, CH
3
(CH
2
2
)
J
11P), 16.6 (d, JC−P = 5.8 Hz,
Classical heating: 1 h, 30–85 C, yield: 85%. Mi-
31
1
CH
3
CH
2.8 (s, CH
40.6 Hz, CH
CH CH (CH
5.6 Hz, CH CH
2
OP), 22.4 (d,
C−P = 5.8 Hz, CH
2
CH
2
P),
crowave: 2 min, 100 W, yield: 95%. P { H} NMR
1
1
2
1
CH
3
CH (CH
2
2
)
10P), 25.7 (d,
J
C−P
=
(CDCl , 80.9 MHz, 298 K): 32.0. H RMN (CDCl ,
3
3
3
2
P), 29.2–29.4–29.5–29.7–29.8–29.9 (s,
500 MHz, 298 K): 1.26 (m, 12H, J
H−H
= 6.7 Hz, CH ),
3
3
3
2
2
2
)
6
CH
CH P), 32.0 (s, CH
C−P = 5.8 Hz, CH OP). m/z (MH ):
07.17, Calcd: 307.23.
2
CH
2
CH
2
P), 30.7 (d, JC−P
=
1.43 (m, 2H, CH CH CH P), 1.57 (m, 4H, CH CH P),
2
2
2
2
2
1
13
1
2
2
2
3
CH CH (CH
2
2
2
)
9
1.66 (m, 4H, CH P), 4.0 (m, 8H, CH OP). C { H}
2
2
2
+
3
P), 61.6 (d,
J
2
NMR (CDCl , 125.9 MHz, 298 K): 16.6 (d, J
=
=
3
C−P
2
3
5.8 Hz, CH ), 22.2 (d,
J
= 5.9 Hz, CH CH P),
3
C−P
2
3
2
1
2
5.6 (d,
J
C−P = 142.6 Hz, CH
2
P), 31.6 (t,
J
C−P
2
2
Diethylisopropylphosphonate (2). Microwave:
15.6 Hz, CH CH P), 61.5 (d, J
= 5.8 Hz, CH OP).
2
2
C−P
3
1
1
+
1
8
2
1
CH
CH
0 × 2 min, 100 W, yield: 30%. P { H} NMR (CDCl
3
,
m/z (MH ): 359.09. Calcd 359.16.
1
0.9 MHz, 298 K): 35.8, H NMR (CDCl
3
, 500 MHz,
3
3
98 K): 1.11 (dd, 6H,
J
H−H = 6.5 Hz,
J
H−P
=
Tetraethyl Decane-1,10-diyldiphosphonate (7).
3
◦
1.7 Hz CH CH-P), 1.25 (t, 6H,
3
J
H−H = 6.9 Hz,
Classical heating: 2 h, 85 C, yield: 90%. Microwave:
3
3
1
1
3
CH
2
OP), 4.03 (dd, 4H, JH−H = JH−P = 6.5 Hz
3 min, 100 W, yield: 90%. P { H} NMR (CDCl ,
3
13
1
1
2
OP). C { H}NMR (CDCl
3
, 125.9 MHz, 298 K):
CHP), 16.6 (d,
80.9 MHz, 298 K): 33.0, H NMR (CDCl , 500 MHz,
3
2
3
16.1 (d,
J
C−P = 5.8 Hz, CH
3
J
C−P
298 K): 1.20 (m, 10H, CH CH CH P), 1.25 (t, 12H,
2
2
2
1
3
=
5.8 Hz, CH
3
CH
2
OP), 25.8 (d,
CHP), 61.7 (d, JC−P = 5.8 Hz, CH
J
C−P = 142.6 Hz,
J
= 7.0 Hz, CH ), 1.49–1.52 (m, 4H, CH CH P),
13
2 2
H−H
3
2
2
2
2
OP).
1.59–1.66 (m, 4H, CH P), 4.00 (m, 8H, CH OP).
C
1
{
H} NMR (CDCl
3
, 125.9 MHz, 298 K): 16.6 (d,
3
2
Diethyl Nonan-2-phosphonate (3). Microwave:
J
C−P = 5.8 Hz, CH3), 22.5 (d,
J
C−P = 3.9 Hz,
P), 25.8 (d, JC−P = 140.6 Hz, CH
CH CH CH P), 30.7 (d,
CH P), 61.5 (d,
3
1
1
1
3
5 min, 100 W, yield: 30%
P { H} NMR
CH
2
CH
2
2
P), 29.17–
1
(CDCl
3
, 80.9 MHz, 298 K): 35.8. H NMR (CDCl
3
,
29.33–29.42–29.56 (s, CH
2
2
2
2
3
3
2
500 MHz, 298 K): 0.86 (t, 3H,
J
J
H−H = 6.5 Hz,
J
C−P = 17.6 Hz, CH
2
CH
2
2
J
C−P
=
3
+
CH
3
(CH
2
)
6
CHP), 1.13 (dd, 3H,
H−H = 6.5 Hz,
7.8 Hz, CH
2
OP). m/z (MH ): 415.25. Calcd: 415.23.
Heteroatom Chemistry DOI 10.1002/hc

Microwave Michaelis–Becker Synthesis of Diethyl Phosphonates, Tetraethyl Diphosphonates, and Their Total or Partial Dealkylation 375
Tetraethyl Dodecane-1, 12- diyldiphosphonate (8).
closed with a calcium chloride tube. The reaction
mixture was then irradiated at 50 W for 2–3 min.
◦
Classical heating: 2 h, 85 C, yield: 90%. Microwave:
3
1
1
3
8
min, 100 W, yield: 90%. P { H} NMR (CDCl
3
,
After evaporation of the solvent and the ClSiMe
3
,
1
0.9 MHz, 298 K): 33.6. H NMR (CDCl
3
, 500 MHz,
the silylated intermediaries were hydrolyzed with
31
2
98 K): 1.24 (s, 12H, CH
2
CH
), 1.31–1.33 (m, 4H, CH
P), 1.51–1.56 (m, 4H, CH CH P), 1.63–1.71
m, 4H, CH P), 4.05 (m, 8H, CH
NMR (CDCl
2
CH
2
CH
2
P), 1.30 (t, 12H,
methanol by stirring for 10 min (followed by
P
3
J
H−H = 7.0 Hz, CH
3
2
NMR). The methanol was evaporated; acetonitrile
was added to the residue, the stirring of this solution
resulted in the formation of a beige solid. The solid
was filtered off, washed several time with cold
acetone.
CH
(
2
CH
2
2
2
13
1
2
2
OP). C { H}
3
3
, 125.9 MHz, 298 K): 16.6 (d, JC−P
=
3
5
2
CH
CH
.8 Hz, CH
3
), 22.5 (d,
J
C−P = 3.9 Hz, CH
2
CH
2
P),
1
5.8 (d, JC−P = 140.6 Hz, CH
2
P), 29.2–29.5–29.7 (s,
3
CH
2
CH
2
CH
2
P), 30.7 (d, JC−P = 17.5 Hz, CH
2
CH
2
Dodecylphosphonic acid (10). Aspect: White
2
2
◦
31
1
P), 61.6 (d, JC−P = 5.8 Hz, CH
2
OP). IR (KBr)
powder. mp: 96 C. Isolated yield: 80%. P { H}
2
−
1
1
ν/(cm ): 1248 (P O), 1030 (P O).
NMR (CD
3
OD, 80.9 MHz, 298 K): 34.0. H NMR
3
(
CD
6.7 Hz, CH
CH CH CH
1.71 (m, 4H, CH
125.9 MHz, 298 K): 14.5 (s, CH
3
OD, 500 MHz, 298 K): 0.9 (t, 3H,
(CH P), 1.29 (m, 18H, CH
P) 1.41(m, 2H, CH CH CH P), 1.57–
P). C{ H} NMR (CD OD,
(CH 11P), 23.8 (s,
10P), 24.0 (d, JC−P = 5.8 Hz, CH CH
C−P = 138.9 Hz, CH P), 30.4–30.6–
30.7–30.9 (s, CH CH CH (CH CH CH CH P), 31.9
15.6 Hz, CH CH CH P), 33.2 (s,
(CH P), 61.6 (d,
J
H−H
(CH
=
Synthesis of Tetraethyl Methylenediphosphonate
9). Synthesis of compound 9 was compared to
3
2
)
10CH
2
3
2 8
)
(
2
2
2
2
2
2
13
1
the methodology originally described by Villemin
et al. (1 month reaction, yield 50% after distilla-
tion). Using microwave irradiation, it was obtained
as follows:. An excess of dichloromethane (15 mL)
was added to a solution of sodium diethylphosphite
2
CH
2
3
3
2
)
2
CH
P), 28.2 (d,
3
CH
2
(CH
2
)
2
2
1
J
2
3
2
2
2
)
6
2
2
2
3
(
20 mmol) in acetonitrile (15 mL) prepared as de-
(d, JC−P
=
2
2
2
2
scribed before. A reflux condenser was then placed,
the setup closed with a calcium chloride tube. The
reaction mixture was then irradiated for a total of
CH
3
CH
2
CH
2
2
)
9
+
J
C−P = 5.8 Hz,
CH
2
OP). m/z (MH ): 251.14. Calcd 251.17.
2
0 min at 100 W. To avoid rapid evaporation of
dichloromethane, the irradiation was done in 10 ×
min runs separated by quick cooling in an ice bath.
Hexane-1,6-diyldiphosphonic acid (11). Aspect:
◦
31
White powder. mp: 198 C. Isolated yield: 75%.
P
H
1
1
2
{ H} NMR (CD
NMR (CD
CH CH CH
{ H} NMR (CD
CH CH
P), 28.0 (d, JC−P = 138.6 Hz, CH
C−P = 15.6 Hz, CH CH CH
Calcd 247.14.
3
OD, 80 MHz, 298 K): 31.0,
After evaporation of the unreacted dichloromethane,
an equivalent of sodium diethylphosphite (20 mmol)
in acetonitrile (15 mL) was added to the reaction
mixture. The mixture was then irradiated for 10 min.
After evaporation of the solvent, the residue was
treated as described for compounds (6–8). The crude
yellow oil was purified by vacuum distillation to
3
OD, 500 MHz, 298 K): 1.45 (m, 4H,
13
2
2
2
P), 1.60–1.73 (m, 8H, CH
2
CH
2
P).
C
1
3
OD, 125 MHz, 298 K): 23.3 (s,
1
2
2
2
P), 31.3 (d,
3
+
J
2
2
2
P). m/z (MH ): 246.97.
31
1
give colorless oil (yield 50%). P { H} RMN (CDCl
3
,
Decane-1,10-diyldiphosphonic acid (12). As-
1
◦
80.9 MHz, 298 K): 19.4. H NMR (CDCl
3
, 200 MHz,
pect: white powder. Mp: 170 C. Isolated Yield:
3
31
1
1
J
298 K), 1.30 (t, 12H, JH−H = 6.8 Hz, CH
3
), 2.40 (t,
OP).
82%. P { H} NMR (CD
3
OD, 80.9 MHz, 298 K):
3
1
H−P = 21.0 Hz, 2H, CH P), 4.10 (m, 8H, CH
2
2
31.4.
H
NMR (CD
3
OD, 500 MHz, 298 K):
CH P), 1.31–1.33 (m, 4H,
P), 1.51–1.54 (m, 4H, CH CH P), 1.56–
1
.23 (m, 8H,CH
CH CH CH
.63 (m, 4H, CH
2
CH
2
CH
2
2
2
2
2
2
2
Synthesis of Diphosphonic Acids
13
1
1
2
P).
C { H} NMR (CD
3
OD,
2
Synthesis of Diphosphonic Acids Using Bro-
motrimethylsilane. The compounds are obtained
according to the method originally descried by
Kishore et al. [38].
125.9 MHz, 298 K): 24.0 (d,
J
C−P = 3.9 Hz,
1
CH
2
CH
2
P), 28.2 (d, JC−P = 138.7 Hz, CH
2
P), 30.4–
3
30.6–30.8 (s, CH
2
CH
P).
2
CH
2
CH
2
P), 31.8 (d, JC−P = 17.6
Hz, CH
2
CH
2
CH
2
Synthesis of Diphosphonic Acids Using
Chlorotrimethylsilane and Sodium Iodide. Phospho-
nate (3 g) was dissolved in acetonitrile; this solution
Dodecane-1,12-diyldiphosphonic acid (13). As-
◦
pect: white powder. mp: 172 C. Isolated yield: 90%.
3
1
1
P { H} NMR (CD
3
OD, 80.9 MHz, 298 K): 33.4.
1
was saturated with argon, and 6 equiv. of ClSiMe
3
H NMR (CD OD, 500 MHz, 298 K): 1.25 (s,
3
and 6 equiv. of sodium iodide were added (except
for obtaining compound 10 3 equiv was used). A
reflux condenser was placed, and the setup was
12H,CH
2
CH
2
CH
2
CH
2
P), 1.33 (m, 4H,CH
CH P), 1.55–1.63 (m, 4H,
P). C { H} NMR (CD OD, 125.9 MHz, 298 K):
2
CH
2
CH P),
2
1.49–1.56 (m, 4H, CH
2
2
1
3
1
CH
2
3
Heteroatom Chemistry DOI 10.1002/hc

376 Meziane et al.
2
1
1
2
4.0, (d, JC−P = 5.8 Hz, CH2CH
2
P), 28.2 (d, JC−P
298 K): 33.3. H NMR (CD
1.30 (m, 6H, CH ), 1.32 (m, 8H, CH
1.39–1.42 (m, 4H, CH CH CH P), 1.54–1.63 (m, 4H,
CH2 CH P), 1.68–1.75 (m, 4H, CH P), 4.05 (td, 8H,
3
OD, 500 MHz, 298 K):
=
138.6 Hz, CH
2
P), 30.3–30.6 (s, CH
1.8 (d, JC−P = 15.6 Hz, CH CH CH
ν/(cm ): 2345(OH), 1235 (P O).
2
CH
2
CH
2
CH
P). IR (KBr)
2
P),
3
2
CH CH CH P),
2
2
2
3
3
2
2
2
2
2
2
−
1
2
3
2
3
13
1
J
CD
CH
J
H−H
≈
J
P−H = 7.4 Hz, CH
2
OP). C { H}NMR
3
(
3
OD, 125.9 MHz, 298 K): 16.9 (d, JC−P = 5.8 Hz,
Synthesis of Diethyl Diphosphonic Acid Esters
15–17)
2
3
), 23.7 (d, JC−P = 3.9 Hz, CH
2
CH P), 26.9 (d,
2
(
1
C−P = 140.6 Hz, CH
2
P), 30.4–30.6–30.8 (s, CH
2
3
Tetraethyl phosphonates (10 mmol) were mixed with
sodium iodide (40 mmol), 5 mL of methanol was
added, and the reaction mixture was irradiated at
CH CH CH P), 31.7 (d,
J
C−P
= 17.6 Hz, CH CH
2
2
2
2
2
2
CH P), 62.2 (d, J
2
C−P
= 5.8 Hz, CH OP).
2
1
00 W for 30–40 min (by 10 min run followed by
Diethyl Dodecane-1,12-diylbis(hydrogen Phos-
cooling to room temperature). 50 mL of diethyl
ether was added to separate the unreacted prod-
ucts. The precipitate was then acidified with con-
centrated HCl. After evaporation to dryness, the de-
sired products were dissolved in chloroform. The
formed salts were filtered of, and the solution was
evaporated to give a clear yellow powder. The same
procedure was used for the monodealkylation of
compound 1b.
◦
phonate) (17). Aspect: white powder. mp: 83 C. Iso-
3
1
1
lated yield: 75%. P { H} NMR (CD
3
OD, 80.9 MHz,
OD, 500 MHz, 298 K):
1
2
1
1
4
1
98 K): 35.6. H NMR (CD
3
.29, (m, 6H, CH3), 1.40 (m, 4H, CH
2
CH
2
CH
2
P), 1.56–
CH P),
OD,
.58 (m, 4, CH
.07, (m, 4H, CH
25.9 MHz, 298 K): 16.9 (d,
2
CH
2
P), 1.60–1.72 (m, 4, CH
2
2
13
1
2
OP). C { H} NMR (CD
3
3
JC−P = 5.8 Hz,
2
CH
3
), 23.8 (d,
J
J
C−P = 3.9 Hz, CH
C−P = 140.6 Hz, CH P), 30.3–30.6–30.7 (s,
CH CH CH P), 1.7 (d,
P), 62.2 (d,
CH P), 27.0
2 2
1
(d,
2
3
CH
CH
2
2
2
2
J
C−P = 15.6 Hz,
Ethyl Hydrogen Dodecylphosphonate (14). As-
2
2
CH
2
CH
2
J
C−P = 5.8 Hz, CH
2
OP).
3
1
1
pect: thick oil. Isolated yield: 50%.
NMR (CD
CD OD, 500 MHz, 298 K): 0.9 (t, 3H,
7.0 Hz, CH (CH P), 1.29–1.34 (m, 19H,
CH (CH CH CH CH P and CH CH OP), 1.41 (m,
H, CH CH CH P) 1.67 (m, 2H, CH CH P), 1.77 (m,
H, CH P), 4.09 (m, 2H, CH
OD, 125.9 MHz, 298 K): 14.7 (s, CH
P { H}
+
−1
m/z (MH ): 387.21. Calcd 387.20. IR (KBr) ν/(cm ):
1
3
OD, 80.9 MHz, 298 K): 32.9. H NMR
2
557(OH), 1222 (P O).
3
(
=
3
J
H−H
3
2
)
10CH
2
3
2
)
8
2
2
2
3
2
Synthesis of Phosphonic Acid Functionalized
Resin (18)
2
2
2
2
2
2
2
13
1
2
2
OP). C { H} NMR
®
(
CD
3
3
(CH
2
)
11P),
The NovaSyn TG bromo resin (1 g, substitution 0.3
3
2
−1
1
=
6.9 (d, JC−P = 5.8 Hz, CH
5.8 Hz, CH CH P), 23.9 (s, CH
C−P = 141.1 Hz, CH P), 30.4–30.7–30.8–
0.9–31.0 (s, CH CH CH (CH CH CH CH P),
0.7 (d, JC−P = 15.6 Hz, CH CH CH P), 33.2 (s,
CH CH (CH P), 63.1 (d,
OP).
3
CH
2
OP), 23.6 (d, JC−P
mmol g ) was suspended in acetonitrile (10 mL)
CH (CH 10P),
2
2
)
in a round-bottom flask equipped with a reflux con-
denser. Sodium phosphate (6 equiv, 1.8 mmol) pre-
pared as previously described was added to the flask
and the reaction mixture was then irradiated for
2
2
3
1
2
3
3
6.0 (d,
J
2
3
2
2
2
)
2
2
6
2
2
2
3
2
2
◦
CH
CH
3
2
2
2
)
9
J
C−P = 5.8 Hz,
5 min (5 × 1 min) at 70 W (Tmax = 80 C). The resin
was filtrated, washed successively with water, ace-
tonitrile, dichloromethane, and diethylether and dry
in a desiccator overnight. The resin phosphonate was
suspended in acetonitrile (10 mL) in a round-bottom
flask equipped with a reflux condenser and an argon
bubbling. An excess of trimethylsilylbromide (0.7
mL, 6 mmol) was added, and the reaction mixture
was irradiated (50 W, 2 × 2 min.). Methanol was
2
Diethyl Hexane-1,6-diylbis(hydrogen Phospho-
◦
nate) (15). Aspect: beige powder. mp: 296 C Iso-
31
1
lated yield: 60%. P { H} NMR (CD
3
OD, 200 MHz,
1
298 K): 27.5. H NMR (CD
3
OD, 500 MHz, 298 K):
3
1.23 (t,
CH
J
H−H = 7.5 Hz, 6H, CH
3
), 1.38 (m, 4H,
CH P), 3.88
CH
td, 8H, JH−H ≈ JP−H = 7.5 Hz, CH
NMR (CD
.8 Hz, CH
2
2
CH P), 1.50–1.57 (m, 8H, CH
2
2
2
13
3
3
1
◦
(
2
OP). C { H}
added (10 mL) at 0 C, and the reaction was stirred
3
OD, 500 MHz, 298 K): 17.3 (d, JC−P
=
for 2 h. The resin was then, filtrated, washed succes-
sively with dichloromethane, and diethylether and
dry in a desiccator overnight. To calculate the load-
ing of the obtained resin, 3 × 100 mg of the resin was
treated overnight with an aqueous sodium hydroxide
solution. Conductometric titration was done on the
remaining solutions, and they were also titrated with
an HCl solution. Both methodology gave a loading
3
2
5
3
), 25.0 (d, JC−P = 3.9 Hz, CH
2
CH P), 28.0
2
1
3
(
d, JC−P = 135 Hz, CH
2
P), 32.4 (d, JC−P = 15.6 Hz,
2
CH
2
CH
2
CH
2
P), 60.6 (d, JC−P = 5.7 Hz, CH
2
OP). m/z
+
(
MH ): 302.97. Calcd: 303.10.
Diethyl Decane-1,10-diylbis(hydrogen Phospho-
◦
nate) (16). Aspect: white powder. mp: 86 C. Iso-
lated yield: 65%. P { H} NMR (CD
31
1
−1
3
OD, 80.9 MHz,
of 0.3 mmol g .
Heteroatom Chemistry DOI 10.1002/hc

Microwave Michaelis–Becker Synthesis of Diethyl Phosphonates, Tetraethyl Diphosphonates, and Their Total or Partial Dealkylation 377
REFERENCES
[25] Benezra, C.; Bravet, J. L. Can J Chem 1975, 53,
746.
[26] Harvey, R. G.; De Sombre, E. R. Topics in Phospho-
rous Chemistry; Wiley: New York, 1964.
[27] Francis, M. D.; Martodam, R. R. In The Role of Phos-
phonates in Living Systems; CRC Press: Boca Raton,
FL, 1983, pp. 55–96.
[28] Zolotukhina, M. M.; Krutikov, V. I.; Lavrent’ev, A. N.
Russ Chem Rev 1993, 62, 647.
[29] Arnold, D. I.; Ouyang, X.; Clearfield, A. Chemi Mater
2002, 14, 2020.
[30] Chiarizia, R.; McAlister, D. R.; Herlinger, A. W.;
Bond, A. H. Solv Extr Ion Exch 2001, 19, 261.
[31] Chowdhury, D. A.; Kamata, S. Solv Extr Ion Exch
1997, 15, 231.
[32] Chen, R.; Schlossman, A.; Breuer, E.; H a¨ agele, G.;
Tillmann, C.; Van Gelder, J. M.; Golomb, G. Het-
eroatom Chem 2000, 11, 470.
[33] Griffith, J. A.; Mc Cauley, D. J.; Barrans, R. E.;
Herlinger, A. W. Synth Commun 1998, 28, 4317.
[34] Villemin, D. Molecules 2000, 5, M131.
[35] Ebetino, F. H. Phosphorus, Sulfur Silicon Relat Elem
1999, 144–146, 9.
[36] McKenna, C. E.; Higa, M. T.; Cheung, N. H.;
McKenna, M. C. Tetrahedron Lett 1977, 2, 155.
[37] Morita, T.; Okamoto, Y.; Sakurai, H. Bull Chem Soc
Jpn 1981, 54, 267.
[38] Kishore Kumar, G. D.; Saenz, D.; Lokesh, G. L.;
Natarajan, A. Tetrahedron Lett 2006, 47, 6281.
[39] Stepinski, D. C.; McAlister, D. R.; Zalupski, P. R.;
Chiarizia, R.; Herlinger, A. W. Solv Extr Ion Exch
2004, 22, 89.
[40] Urban, V.; Chiarizia, R.; Herlinger, A. W.; Ku, C. Y.;
Thiyagarajan, P. Physica B: Condensed Matter 1997,
241, 355–357.
[41] Pietzonka, T.; Damon, R.; Russell, M.; Wattanasin, S.
Bioorg Med Chem Lett 1996, 6, 1951.
[42] Lagarrigue, M.; Boss e´ e, A.; B e´ gos, A.; Varenne, A.;
Gareil, P.; Bellier, B. J. Chromatgr A 2006, 1137, 110.
[43] Norbeck, D. W.; Kramer, J. B.; Lartey, P. A. J Org
Chem 1987, 52, 2174.
[44] Niemi, R.; Turhanen, P.; Veps a¨ l a¨ inen, J.; Taipale, H.;
J a¨ rvinen, T. Eur J Pharma Sci 2000, 11, 173.
4
[
[
[
1] Fields, S. C. Tetrahedron 1999, 55, 12237.
2] Engel, R. Chem Rev 1977, 77, 349.
3] Ternan, N. G.; McGrath, J. W.; McMullan, G.; Quinn,
J. P. World J Microbiol Biotechnol 1998, 14, 635.
4] Guest, D.; Grant, B. Biol Rev 1991, 66, 159.
5] Eto, M. In Handbook of Organophosphorus Chem-
istry; Marcel Dekker: New York, 1992; p. 807.
6] Clearfield, A. Curr Opin Solid State Mater Sci 2002,
[
[
[
6
, 495.
[
[
7] Clearfield, A. J. Alloys Compd 2006, 418, 128.
8] Abderrahim, O.; Didi, M. A.; Moreau, B.; Villemin, D.
Solv Extr Ion Exch 2006, 24, 943.
[
9] Trochimczuk, A. W. Solv Extr Ion Exch 2001, 19, 301.
[
[
[
10] Chougrani, K.; Boutevin, B.; David, G.; Boutevin, G.
Eur Polym J 2008, 44, 1771.
11] Quittmann, U.; Lecamp, L.; El Khatib, W.; Boulos,
Y.; Bunel, C. Macromolec Chem Phys 2001, 202, 628.
12] Gentilhomme, A.; Cochez, M.; Ferriol, M.; Oget, N.;
Mieloszynski, J. L. Polym Degrad Stab 2005, 88, 92.
13] Alexandratos, S. D. J. Hazard Mater 2007, 139, 467.
14] Bhattacharya, A. K.; Thyagarajan, G. Chem Rev 1981,
[
[
8
1, 415.
[
[
15] Pelaprat, N.; Brondino, C.; Rigal, G.; Boutevin, B. Eur
Polym J 1996, 32, 761.
16] Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J.
Tetrahedron 2001, 57, 9225.
[
[
17] Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199.
18] Kabachnik, M.; Zobnina, E.; Beletskaya, I. Synlett
2
005, 1393.
19] Kaboudin, B.; As-habei, N. Tetrahedron Lett 2003,
4, 4243–4245.
[
4
[
[
20] Kaboudin, B.; Rahmani, A. Synthesis 2003, 2705.
21] Mu, X.-J.; Lei, M.-Y.; Zou, J.-P.; Zhang, W. Tetrahe-
dron Lett 2006, 47, 1125.
[
22] Villemin, D.; Simeon, F.; Decreus, H.; Jaffres, P.-A.
Phosphorus, Sulfur Silicon Relat Elem 1998, 133,
2
09.
[
[
23] Belkhouche, N.-E.; Didi, M. A.; Romero, R.; J o¨ nsson,
˚
J. A.; Villemin, D. J Memb Sci 2006, 284, 398.
24] Garner, A. Y.; Chapin, E. C.; Scanlon, P. M. J Org
Chem 1959, 24, 532.
Heteroatom Chemistry DOI 10.1002/hc