Micellar solution of sodium dodecyl sulfate (SDS) catalyzes Kabacknik-Fields reaction in aqueous media

Article abstract of DOI:10.1055/s-0029-1216789

A new, convenient and high-yielding procedure for the one-pot synthesis of diethyl α-aminophosphonates from aldehydes, amines and diethyl phosphite (Kabacknik-Fields reaction) in SDS micellar solution in aqueous media is described. The synthesis of aaminophosphonates in the present study represents a three-component reaction in which no intermediate formation of either an imine or α-hydroxyphosphonate was observed. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216789

PAPER
1909
Micellar Solution of Sodium Dodecyl Sulfate (SDS) Catalyzes Kabacknik–
Fields Reaction in Aqueous Media
K
abacknik–Fi
a
r
n in A
q
a
ueous Media Sobhani,* Asieh Vafaee
Department of Chemistry, College of Sciences, Birjand University, Birjand 414, Iran
Fax +98(561)2502009; E-mail: ssobhani@birjand.ac.ir; E-mail: sobhanisara@yahoo.com
Received 30 January 2009; revised 7 February 2009
This paper is dedicated to Professor H. Firouzabadi on the occasion of his 65th birthday and his honorable retirement.
opment of surfactant-aided organic reactions is still at a
preliminary stage.8
Abstract: A new, convenient and high-yielding procedure for the
one-pot synthesis of diethyl a-aminophosphonates from aldehydes,
amines and diethyl phosphite (Kabacknik–Fields reaction) in SDS
micellar solution in aqueous media is described. The synthesis of a-
aminophosphonates in the present study represents a three-compo-
nent reaction in which no intermediate formation of either an imine
or a-hydroxyphosphonate was observed.
In recent years, considerable interest has been focused on
the synthesis of a-aminophosphonates because they are
considered to be structural analogues of the corresponding
a-amino acids and transition-state mimics of peptide hy-
drolysis. In this connection, the utilities of a-aminophos-
phonates as peptide mimics,9 enzyme inhibitors,10 hapten
of catalytic antibodies,11 antibiotics and pharmacological
agents,12 are well documented. The addition of phospho-
rus nucleophiles to imines is a general synthetic method
reported for the synthesis of a-aminophosphonates. This
reaction is usually catalyzed by Lewis acids such as
SnCl2, SnCl4, ZnCl2 and MgBr2. However, these reactions
do not proceed by a one-pot synthetic method from a car-
bonyl compound, an amine and a phosphite ester via
Kabacknik–Fields reaction because the generation of wa-
ter during the course of the reaction can decompose or de-
activate the Lewis acids.13 This drawback has been
overcome by a recent method using a combination of lan-
thanide triflates and magnesium sulfate.14 However, the
utilization of an organic solvent and either molecular
sieves or magnesium sulfate is required. Other methodol-
ogies reported have further disadvantages, such as: pro-
longed reaction times, low yields of the products, the
requirement for special apparatus or large amounts of ad-
ditives, solid supports or catalyst which would eventually
result in the generation of large amounts of toxic waste, or
the use of malodorous trialkyl phosphite as the phospho-
rus nucleophile, or use of toxic solvents.15 Moreover, the
efficiency of the procedures reported is mostly limited to
the reaction of highly electrophilic carbonyl compounds
and strongly nucleophilic amines.
Key words: aldehydes, amines, a-aminophosphonates, micelles,
sodium dodecyl sulfate, aqueous media
Use of aqueous media as a reaction solvent has attracted
much attention in synthetic organic chemistry for several
reasons.1 In comparison with organic solvents, water is
cheap, safe, reduces the use of harmful organic solvents
and leads to the development of environmentally friendly
chemical processes.2 In addition, reactions in aqueous me-
dia illustrate unique reactivities and selectivities that are
not usually observed in organic media.3 However, organic
solvents are still used instead of water for mainly two rea-
sons. First, most organic substrates are not soluble in wa-
ter and, as a result, water cannot function as a reaction
medium. Second, many reactive substrates, reagents and
catalysts are sensitive towards water and are decomposed
or deactivated in aqueous media. A possible way to im-
prove the solubility of substrates is the use of surface-
active reagents that can form micelles4 or vesicular struc-
tures in aqueous media. Micelles are dynamic clusters of
surfactant molecules which posses both hydrophilic and
hydrophobic structures.5 It is well established that, in
many cases, the rates and pathways of many chemical re-
actions can be altered by performing the reactions in mi-
cellar media instead of pure bulk solvents. Micelles can
concentrate the reactants within a small volume, stabilize
substrates, intermediates or products and orient substrates
so that ionization potential, oxidation–reduction proper-
ties, dissociation constants, physical properties and reac-
tivities are changed. Thus, they can alter the reaction rate,
mechanism, regio- and stereoselectivity of the reaction.6
As part of our efforts to introduce new methods for the
synthesis of phosphonate derivatives,16 here we report the
use of micellar solutions of sodium dodecyl sulfate (SDS)
in water as an efficient media for the one-pot synthesis of
a-aminophosphonates via Kabacknik–Fields reaction.
Initially, we examined the feasibility of the coupling reac-
tion between 4-methoxybenzaldehyde, 4-nitroaniline and
diethyl phosphite as a model, and used micellar solutions
of different surfactants at their critical micellar concentra-
tions (CMC)17 in water. It is important to note that the
presence of the methoxy group in 4-methoxybenzalde-
hyde reduces the electrophilicity of the carbonyl carbon
through resonance, and the strong electron-withdrawing
The use of micellar and vesicle-forming surfactants as cat-
alysts is widespread and has been investigated in detail for
different reactions in aqueous solutions.7 However, from
the viewpoints of practicality and applicability, the devel-
SYNTHESIS 2009, No. 11, pp 1909–1915
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Advanced online publication: 30.04.2009
DOI: 10.1055/s-0029-1216789; Art ID: Z01809SS
© Georg Thieme Verlag Stuttgart · New York

1910
S. Sobhani, A. Vafaee
PAPER
property of nitro group in 4-nitroaniline decreases the nu- To assess the generality and scope of this synthetic meth-
cleophilicity of the amine group. Thus, the combination of od, the reaction of various structurally diverse aldehydes
these substrates constitutes a model reaction for evaluat- and ketones were examined in the presence of SDS micel-
ing the efficiency of a catalyst.
lar solution (Scheme 1). The results are summarized in
Table 1.
Among the micellar solutions tested, SDS turned out to be
the most effective micellar media, leading to the desired
product in 86% yield after one hour at 50 °C. Similar re-
actions in the presence of cetyltrimethylammonium bro-
mide (CTAB) as a cationic micelle and Triton X-100 as a
neutral micelle at their CMCs in water, did not proceed to
completion even after 24 hours, and the desired product
was produced in 45 and 50% yields, respectively. In order
to show the catalytic effect of micellar SDS, the corre-
sponding reaction was examined in pure water; this reac-
tion remained incomplete and only 30% of the desired
product was obtained after 24 hours.
O
O
R1
R1
P(OEt)2
micellar SDS solution
2
3
+
+ R R NH
O
HP(OEt)2
H2O, 50 °C
5–60 min
70–98%
H
NR2R3
R1 = aryl, heteroaryl, allyl, alkyl
R2 = aryl, alkyl
1–25
R3 = alkyl, H
Scheme 1
Table 1 One-Pot Synthesis of Diethyl a-Aminophosphonates by Kabacknik–Fields Reaction of Aldehydes, Amines and Diethyl Phosphite
in SDS Micellar Solution at its Critical Micellar Concentration (CMC) in Aqueous Media
Entry Aldehyde
Amine
Product
Time (min) Yield (%)a
O
P(OEt)2
NH2
NH2
NH2
CHO
1
1
60
15
45
30
86
95
95
98
N
H
NO2
O2N
MeO
MeO
O
CHO
P(OEt)2
OMe
2
3
4
2
3
4
N
H
NO2
O2N
OMe
O
P(OEt)2
CHO
CHO
N
H
CN
NC
MeO
MeO
MeO
O
P(OEt)2
NH2
N
H
COOH
HOOC
MeO
MeO
O
NH2
P(OEt)2
CHO
5
5
15
95
N
H
MeO
Br
Br
O
O
O
P(OEt)2
CHO
CHO
CHO
NH2
6
7
8
6
7
8
15
5
95
95
98
N
H
Cl
MeO
MeO
MeO
Cl
MeO
MeO
MeO
P(OEt)2
NH2
N
H
OMe
MeO
P(OEt)2
NH2
30
N
H
Synthesis 2009, No. 11, 1909–1915 © Thieme Stuttgart · New York

PAPER
Kabacknik–Fields Reaction in Aqueous Media
1911
Table 1 One-Pot Synthesis of Diethyl a-Aminophosphonates by Kabacknik–Fields Reaction of Aldehydes, Amines and Diethyl Phosphite
in SDS Micellar Solution at its Critical Micellar Concentration (CMC) in Aqueous Media (continued)
Entry Aldehyde
Amine
Product
Time (min) Yield (%)a
O
P(OEt)2
CHO
CHO
CHO
9
9
20
30
60
95
85
70
NH2
N
H
MeO
MeO
MeO
O
P(OEt)2
NH2
10
10
11
N
H
MeO
O
P(OEt)2
11
N
H
N
H
MeO
O
P(OEt)2
N
CHO
CHO
12
12
30
86
O
NH
O
MeO
MeO
MeO
O
P(OEt)2
N
13
13
14
60
30
93
95
NH
MeO
O
NH2
P(OEt)2
14
N
H
CHO
O
N
O
O
P(OEt)2
CHO
NH2
15
15
30
85
N
H
N
O
P(OEt)2
NH
CHO
NH2
16
17
16
17
30
5
85
98
N
H
O2N
N
H
NO2
O
P(OEt)2
NH2
CHO
N
H
O
O
NH2
NH2
NH2
P(OEt)2
18
19
20
18
19
20
60
60
15
92
CHO
CHO
N
H
P(OEt)2
96
N
H
O
O
P(OEt)2
CHO
(EtO)2P
97b
OHC
PhHN
NHPh
Synthesis 2009, No. 11, 1909–1915 © Thieme Stuttgart · New York

1912
S. Sobhani, A. Vafaee
PAPER
Table 1 One-Pot Synthesis of Diethyl a-Aminophosphonates by Kabacknik–Fields Reaction of Aldehydes, Amines and Diethyl Phosphite
in SDS Micellar Solution at its Critical Micellar Concentration (CMC) in Aqueous Media (continued)
Entry Aldehyde
Amine
Product
Time (min) Yield (%)a
O
P(OEt)2
CHO
NH2
21
21
22
23
5
45
5
95
85
93
N
H
CHO
O
P(OEt)2
NH2
22
23
N
H
O
P(OEt)2
NH2
CHO
N
H
Cl
Cl
O
O
Cl
Cl
P(OEt)2
NH2
CHO
24
25
24
25
15
30
95
86
N
H
Cl
Cl
P(OEt)2
NH2
CHO
N
H
Cl
Cl
a Reaction conditions: benzaldehyde (1 equiv), amine (1 equiv), diethyl phosphite (4 equiv), 50 °C.
b Ratio of benzaldehyde–aniline–diethyl phosphite, 1:2:8.
As can be seen from Table 1 entries 1 and 2, the present However, the results were not as positive as those present-
method is efficient for the synthesis of diethyl a-amino- ed above.
phosphonates 1 and 2 from the coupling reaction of 4-
methoxy- and 2-methoxybenzaldehyde (representative of
less electrophilic aldehydes), with 4-nitroaniline (repre-
sentative of a less nucleophilic aniline). The reactions of
It should be noted that no competitive side reactions, such
as the formation of a-hydroxyphosphonates, were ob-
served in these transformations. These observations
prompted us to study the possibility of forming a-hy-
4-methoxybenzaldehyde also proceeded well with a vari-
droxyphosphonate as an intermediate in these reactions.
ety of substituted anilines with electron-donating and
We have found that the treatment of 4-methoxybenzalde-
electron-withdrawing groups (entries 3–8). Both aromatic
hyde with diethyl phosphite in SDS micellar solution in
amines and aliphatic amines (primary and secondary)
aqueous media at 50 °C, did not produce any significant
were effective candidates for this transformation (entries
amount of the corresponding a-hydroxyphosphonate even
after 24 hours (IR, NMR, MS).
9–13). Acid-sensitive aldehydes, such as furan-2-carbal-
dehyde, pyridine-3-carbaldehyde, indole-3-carbaldehyde,
We have also studied the possibility of imine formation as
cinnamaldehyde and crotonaldehyde, underwent smooth
another potential intermediate, however, no such species
reactions without any decomposition or polymerization
were detected by IR, NMR or MS in the reaction of 4-
under the present reaction conditions (entries 14–18). The
methoxybenzaldehyde and 4-nitroaniline in SDS micellar
coupling reaction of butyraldehyde as an aliphatic alde-
solution in aqueous media at 50 °C.
hyde with aniline and diethyl phosphite, gave the corre-
sponding product in high yield (entry 19). Difunctional
aminophosphonate 20 was also prepared successfully by
the presented method in 97% yield (entry 20). Apart from
the above aldehydes, a range of substituted benzaldehydes
were also selected for the one-pot coupling reactions (en-
tries 21–25). It was found that there were no remarkable
electronic or steric effects on the progress of these reac-
tions and the desired products were isolated in high yields.
We have also studied the reaction of ketones with aniline
and diethyl phosphite under the same reaction conditions.
These observations represent a one-pot, three-component
reaction for the synthesis of a-aminophosphonates in SDS
micellar solution. The catalytic effect of micellar SDS in
these reactions can be explained as follows: molecules of
aldehydes, amines and diethyl phosphite are accumulated
inside the droplet vesicles of micellar SDS. In these micel-
lar droplets, the distance between the reactive species de-
crease drastically, which facilitates the progress of the
reaction and causes the reaction rate enhancement. The
comparably hydrophobic nature of the a-aminophospho-
Synthesis 2009, No. 11, 1909–1915 © Thieme Stuttgart · New York

PAPER
Kabacknik–Fields Reaction in Aqueous Media
1913
Diethyl (4-Methoxyphenyl)-N-(phenyl)aminomethylphospho-
nate reaction products, with the hydrophobic core of the
micellar droplet could also be considered as another factor
in the rate enhancement of the reaction. This explanation
is schematically presented by Figure 1.
nate (8)
IR (KBr): 3303 (NH) cm–1.
1H NMR (CDCl3): d = 1.02–1.08 (m, 3 H, OCH2CH3), 1.18–1.22
(m, 3 H, OCH2CH3), 3.70 (s, 3 H, OCH3), 3.63–3.69, 3.84–3.89,
4.01–4.06 (m, 4 H, OCH2CH3), 4.58–4.67 (m, 2 H, CH, NH), 6.50–
6.63 (m, 3 H, C6H4, C6H5), 6.77–6.81 (m, 2 H, C6H4, C6H5), 7.00–
7.03 (m, 2 H, C6H4, C6H5), 7.29–7.31 (m, 2 H, C6H4, C6H5).
H2O
H2O
O
O
H2O
O
H2
H2O
H2O
13C NMR (CDCl3): d = 16.7 (d, 3JC,P = 5.8 Hz, OCH2CH3), 16.8 (d,
HP(OEt)2
O
H2O
R
H
P(OEt)2
1
3JC,P = 5.8 Hz, OCH2CH3), 55.7 (d, JC,P = 152.1 Hz, CH), 55.61
R
(OCH3), 63.5 (OCH2CH3), 114.3–114.4, 118.7, 129.3–129.5 (C6H5,
C6H4).
MS (70 eV): m/z = 349 [M+], 212 [M – P(O)(OEt)2].
R'NH2
NHR'
H2O
H2O
H2O
H2O
H2O
Anal. Calcd for C18H24NO4P: C, 61.88; H, 6.92; N, 4.01. Found: C,
61.85; H, 6.90; N, 3.99.
hydrophilic core
hydrophobic core
Diethyl (2-Furyl)-N-(phenyl)aminomethylphosphonate (14)
IR (KBr): 3298 (NH) cm–1.
Figure 1
1H NMR (CDCl3): d = 1.18–1.36 (m, 6 H, OCH2CH3), 3.85–4.21
(m, 4 H, OCH2CH3), 4.52 (br s, 1 H, NH), 4.67 (dd, 2JH,H = 7.0 Hz,
2JP,H = 22.5 Hz, 1 H, CH), 6.32–6.38 (m, 2 H, C4H3O, C6H5), 6.65–
6.77 (m, 3 H, C4H3O, C6H5), 7.12–7.38 (m, 2 H, C4H3O, C6H5), 8.20
(s, 1 H, C4H3O, C6H5).
In conclusion, we have reported the synthesis of a range
of a-aminophosphonates by the one-pot reaction of alde-
hydes (including less electrophilic aldehydes), amines (in-
cluding less nucleophilic aniline) and diethyl phosphite
(Kabacknik–Fields reaction) catalyzed by SDS micellar
solutions in aqueous media. The synthesis of a-amino-
phosphonates in the present study represents a three-com-
ponent reaction in which no intermediate formation of
either an imine or a-hydroxyphosphonate was observed.
With the increasing concern over the need for green syn-
thetic procedures, the advantages such as: (i) using water
as a solvent; (ii) high yields; (iii) excellent chemoselectiv-
ity and (iv) ease of product isolation, fulfill the triple bot-
tom line philosophy of green chemistry and make the
present methodology environmentally benign. Short reac-
tion times, use of diethyl phosphite instead of the unpleas-
ant-smelling triethyl phosphite and no by-product
13C NMR (CDCl3): d = 16.30 (d, 3JC,P = 5.7 Hz, OCH2CH3), 16.4 (d,
3JC,P = 5.7 Hz, OCH2CH3), 50.3 (d, 1JC,P = 159.5 Hz, CH), 63.3 (d,
2
2JC,P = 7.0 Hz, OCH2CH3), 63.5 (d, JC,P = 7.0 Hz, OCH2CH3),
108.8, 110.8, 114.0, 118.9, 129.2, 142.5, 149.4 (C4H3O, C6H5).
MS (70 eV): m/z = 309 [M+], 172 [M – P(O)(OEt)2].
Anal. Calcd for C15H20NO4P: C, 58.25; H, 6.52; N, 4.53. Found: C,
58.23; H, 6.50; N, 4.51.
Diethyl 3-Phenyl-1-(phenylamino)allylphosphonate (17)
IR (KBr): 3297 (NH) cm–1.
1H NMR (CDCl3): d = 1.26–1.33 (m, 6 H, OCH2CH3), 4.10–4.23
(m, 5 H, OCH2CH3, NH), 4.47 (dd, 2JH,H = 6.0 Hz, 2JP,H = 27.5 Hz,
1 H, CH), 6.24–6.30 (m, 1 H, CH=CH), 6.68–6.77 (m, 4 H, C6H5,
CH=CH), 7.14–7.37 (m, 7 H, C6H5).
formation, are further advantages of the present method- 13C NMR (CDCl3):
d
= 22.9–23.1 (OCH2CH3), 60.5 (d,
1JC,P = 153.3 Hz, CH), 69.5 (d, 2JC,P = 7.0 Hz, OCH2CH3), 70.0 (d,
ology.
2JC,P = 7.0 Hz, OCH2CH3), 120.3, 124.9–139.6 (C6H5).
MS (70 eV): m/z = 345 [M+], 208 [M – P(O)(OEt)2].
Chemicals were purchased from Merck or Fluka Chemical Compa-
nies. All of the products are known and were identified by their
spectral data. IR spectra were run on a Perkin–Elmer 780 instru-
ment. NMR spectra were recorded using TMS as standard, on a
Bruker Avance DPX-250 instrument. Mass spectra were recorded
on a Shimadzu GCMS-QP5050A. The purity of the products and
the progress of the reactions were monitored by TLC on silica gel
polygram SILG/UV254 plates. Elemental analyses were obtained us-
ing a Heraeus CHN-O-Rapid analyzer.
Anal. Calcd for C19H24NO3P: C, 66.07; H, 7.00; N, 4.06. Found: C,
66.00; H, 6.68; N, 4.01.
Diethyl (n-Propyl)-N-(phenyl)aminomethylphosphonate (19)
1H NMR (CDCl3): d = 0.84 (t, 2JH,H = 7.2 Hz, 3 H, CH3), 1.09–1.24
(m, 6 H, OCH2CH3), 1.50–1.82 [m, 4 H, (CH2)2CH3], 3.60–3.65 (m,
2
2 H, NH, CH), 3.94–4.09 (m, 4 H, OCH2CH3), 6.58 (d, JH,H = 8.2
2
Hz, 2 H, C6H5), 6.65 (d, JH,H = 7.4 Hz, 1 H, C6H5), 7.09 (t,
2JH,H = 7.6 Hz, 2 H, C6H5).
General Procedure
MS (70 eV): m/z = 285 [M+], 148 [M – P(O)(OEt)2].
Aldehyde (1 mmol), amine (1 mmol) and diethyl phosphite (0.552
g, 4 mmol) were added to a micellar solution of SDS (4 mL,
CMC = 8.1 × 10–3 M) in H2O. The mixture was stirred for the ap-
propriate time at 50 °C (Table 1), then cooled to r.t. and the organic
layer was extracted with EtOAc (2 × 10 mL). The organic layer was
separated, dried over Na2SO4 and filtered. The filtrate was concen-
trated under reduced pressure to give almost pure product. Further
purification was performed by plate chromatography (n-hexane–
EtOAc, 1:1→1:3).
Anal. Calcd for C14H24NO3P: C, 58.93; H, 8.48; N, 4.91. Found: C,
58.90; H, 8.45; N, 4.88.
Diethyl {4-[N-(Phenyl)amino(diethoxyphosphoryl)methyl]phe-
nyl}-N-(phenyl)aminomethylphosphonate (20)
IR (KBr): 3285 (NH) cm–1.
1H NMR (CDCl3): d = 0.84–0.92 (m, 3 H, OCH2CH3), 0.93–0.98
(m, 3 H, OCH2CH3), 1.11–1.20 (m, 6 H, OCH2CH3), 3.30–3.55 (m,
2 H, OCH2CH3), 3.65–3.80 (m, 2 H, OCH2CH3), 3.96–4.03 (m,
4 H, OCH2CH3), 4.65–4.73 (m, 4 H, CH, NH), 6.45–6.49 (m, 4 H,
Synthesis 2009, No. 11, 1909–1915 © Thieme Stuttgart · New York

1914
S. Sobhani, A. Vafaee
PAPER
Diethyl Phenyl-N-(4-chlorophenyl)aminomethylphosphonate
C6H5), 6.57–6.61 (m, 2 H, C6H5), 6.93–6.99 (m, 4 H, C6H5), 7.36 (s,
4 H, C6H4).
13C NMR (CDCl3): d = 15.97–16.38 (OCH2CH3), 55.81 (d,
1JP,C = 150.8 Hz, CH), 63.13–63.35 (OCH2CH3), 113.89, 118.33,
128.19–129.49, 135.56, 146.07–146.30 (C6H5, C6H4).
(25)
IR (KBr): 3287 (NH) cm–1.
1H NMR (CDCl3): d = 0.99–1.03 (m, 3 H, OCH2CH3), 1.18–1.24
(m, 3 H, OCH2CH3), 3.45–3.70 (m, 1 H, OCH2CH3), 3.80–4.00 (m,
1 H, OCH2CH3), 4.02–4.04 (m, 3 H, OCH2CH3, NH), 4.62 (d,
2JP,H = 24.1 Hz, 1 H, CH), 6.41–6.45 (m, 2 H, C6H5, C6H4), 6.93–
6.98 (m, 2 H, C6H5, C6H4), 7.21–7.26 (m, 3 H, C6H5, C6H4), 7.34–
7.38 (m, 2 H, C6H5, C6H4).
MS (70 eV): m/z = 560 [M+], 423 [M – P(O)(OEt)2].
Anal. Calcd for C28H38N2O6P2: C, 59.99; H, 6.83; N, 5.00. Found:
C, 59.90; H, 6.80; N, 4.95.
13C NMR (CDCl3): d = 15.15 (d, 3JP,C = 5.8 Hz, OCH2CH3), 15.40
(d, JP,C = 5.8 Hz, OCH2CH3), 55.14 (d, JP,C = 150.9 Hz, CH),
62.19–62.44 (m, OCH2CH3), 113.97, 122.02, 126.73–127.08,
127.63–127.98, 134.39, 143.76, 143.99 (C6H5, C6H4).
Diethyl Phenyl-N-(phenyl)aminomethylphosphonate (21)
3
1
IR (KBr): 3305 (NH) cm–1.
1H NMR (CDCl3): d = 1.11 (t, 2JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.28
(t, 2JH,H = 7.1 Hz, 3 H, OCH2CH3), 3.59–3.69 (m, 1 H, OCH2CH3),
3.88–3.95 (m, 1 H, OCH2CH3), 4.07–4.16 (m, 2 H, OCH2CH3),
MS (70 eV): m/z = 355 [M+ + 2], 353 [M+], 216 [M – P(O)(OEt)2].
2
4.75 (d, JP,H = 26.4 Hz, 1 H, CH), 4.79 (br s, 1 H, NH), 6.59 (d,
Anal. Calcd for C17H21ClNO3P: C, 57.71; H, 5.98; N, 3.96. Found:
C, 57.69; H, 5.95; N, 3.94.
2JH,H = 7.9 Hz, 2 H, C6H5), 6.68 (t, 2JH,H = 7.3 Hz, 1 H, C6H5), 7.10
2
(t, JH,H = 8.0 Hz, 2 H, C6H5), 7.25–7.35 (m, 3 H, C6H5), 7.47 (d,
2JH,H = 7.4 Hz, 2 H, C6H5).
Acknowledgment
13C NMR (CDCl3): d = 16.6 (d, 3JC,P = 5.8 Hz, OCH2CH3), 16.8 (d,
3JC,P = 5.8 Hz, OCH2CH3), 56.4 (d, 1JC,P = 150.4 Hz, CH), 63.7 (d,
2JC,P = 7.0 Hz, OCH2CH3), 114.2, 118.8, 128.2–129.6, 136.3,
146.6–146.8 (C6H5).
We are thankful to Birjand University Research Council for their
support on this work.
MS (70 eV): m/z = 319 [M+], 182 [M – P(O)(OEt)2].
References
Anal. Calcd for C17H22NO3P: C, 63.94; H, 6.94; N, 4.39. Found: C,
63.92; H, 6.92; N, 4.37.
(1) (a) Li, C. J.; Chan, T. H. Organic Reactions in Aqueous
Media; John Wiley and Sons: New York, 1997. (b)Organic
Reactions in Water; Grieco, P. A., Ed.; Blackie Academic
and Professional: London, 1998.
(2) Anastas, P.; Warner, J. C. Green Chemistry: Theory and
Practice; Oxford University Press: Oxford, 1998.
(3) (a) Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102,
7816. (b) Breslow, R. Acc. Chem. Res. 1991, 24, 159.
(c) Engberts, J. B. F. N.; Blandamer, M. Chem. Commun.
2001, 1701.
Diethyl (4-Cholorophenyl)-N-(phenyl)aminomethylphospho-
nate (23)
IR (KBr): 3299 (NH) cm–1.
1H NMR (CDCl3): d = 1.09 (t, 2JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.21
(t, 2JH,H = 7.1 Hz, 3 H, OCH2CH3), 3.69–4.09 (m, 4 H, OCH2CH3),
2
4.60–4.70 (m, 2 H, CH, NH), 6.48 (d, JH,H = 7.8 Hz, 2 H, C6H4,
C6H5), 6.63 (t, 2JH,H = 7.3 Hz, 1 H, C6H4, C6H5), 7.03 (t, 2JH,H = 7.8
2
Hz, 2 H, C6H4, C6H5), 7.23 (d, JH,H = 8.4 Hz, 2 H, C6H4, C6H5),
(4) (a) Fendler, J. H.; Fendler, E. J. Catalysis in Micellar and
Macromolecular Systems; Academic Press: London, 1975.
(b) Mixed Surfactant Systems; Holland, P. M.; Rubingh, D.
N., Eds.; American Chemical Society: Washington DC,
1992. (c) Structure and Reactivity in Aqueous Solution;
Cramer, C. J.; Truhlar, D. G., Eds.; American Chemical
Society: Washington DC, 1994. (d) Surfactant-Enhanced
Subsurface Remediation; Sabatini, D. A.; Knox, R. C.;
Harwell, J. H., Eds.; American Chemical Society:
Washington DC, 1994. (e) Manabe, K.; Sun, X. M.;
Kobayashi, S. S. J. Am. Chem. Soc. 2001, 123, 10101.
(5) (a) Stein, T. M.; Gellman, S. H. J. Am. Chem. Soc. 1992, 114,
3943. (b) Myers, D. Surfactant Science and Technology;
Wiley-VCH: Weinheim, 1992. (c) Fendler, J. H. Membrane
Mimetic Chemistry; Wiley: New York, 1982.
7.32–7.36 (m, 2 H, C6H4, C6H5).
13C NMR (CDCl3): d = 16.6 (d, 3JC,P = 5.8 Hz, OCH2CH3), 16.8 (d,
3JC,P = 5.8 Hz, OCH2CH3), 55.9 (d, JC,P = 150.5 Hz, CH), 63.7–
1
63.9 (OCH2CH3), 114.2, 119.1, 129.2–129.6, 134.1, 135.0, 146.3–
146.5 (C6H5, C6H4).
MS (70 eV): m/z = 353 [M+], 355 [M + 2], 216 [M – P(O)(OEt)2].
Anal. Calcd for C17H21ClNO3P: C, 57.71; H, 5.98; N, 3.96. Found:
C, 57.69; H, 5.95; N, 3.93.
Diethyl (2,6-Dichlorophenyl)-N-(phenyl)aminomethylphospho-
nate (24)
IR (KBr): 3322 (NH) cm–1.
1H NMR (CDCl3): d = 1.02–1.07 (m, 3 H, OCH2CH3), 1.24–1.29
(m, 3 H, OCH2CH3), 3.81–3.84 (m, 1 H, OCH2CH3), 3.94–4.01 (m,
1 H, OCH2CH3), 4.10–4.19 (m, 2 H, OCH2CH3), 5.40 (t, J = 8.0 Hz,
(6) Tascioglu, S. Tetrahedron 1996, 52, 11113; and references
therein.
3
2
(7) (a) Berezin, I. V.; Martinek, K.; Yatsimirski, A. K. Russ.
Chem. Rev. 1973, 42, 787. (b) Menger, F. M.; Rhee, J. U.;
Rhee, H. K. J. Org. Chem. 1975, 40, 3803. (c) Larpent, C.;
Bernard, E.; Menn, F. B.; Patin, H. J. Mol. Catal. A: Chem.
1997, 116, 277. (d) Dwars, T.; Schmidt, U.; Fischer, C.;
Grassert, I.; Kempe, R.; Fröhlich, R.; Drauz, K.; Oehme, G.
Angew. Chem. Int. Ed. 1998, 37, 2581. (e) Grassert, I.;
Schmidt, U.; Ziegler, S.; Fischer, C.; Oehme, G.
1 H, NH), 5.77 (dd, JH,H = 9.95 Hz, JP,H = 28.6 Hz, 1 H), 6.56–
6.66 (m, 3 H, C6H5, C6H3), 7.01–7.27 (m, 5 H, C6H5, C6H3).
13C NMR (CDCl3): d = 16.11 (d, 3JP,C = 5.8 Hz, OCH2CH3), 16.46
3
1
(d, JP,C = 5.8 Hz, OCH2CH3), 53.14 (d, JP,C = 157.9 Hz, CH),
2
2
63.07 (d, JP,C = 6.8 Hz, OCH2CH3), 63.39 (d, JP,C = 6.8 Hz,
OCH2CH3), 113.28, 113.51, 118.71, 128.34, 129.26, 129.30,
130.47, 130.52, 145.61, 145.86 (C6H5, C6H3).
MS (70 eV): m/z = 391 [M+ + 4], 389 [M+ + 2], 387 [M+], 250 [M –
P(O)(OEt)2].
Tetrahedron: Asymmetry 1998, 9, 4193. (f) Selke, R.; Holz,
J.; Riepe, A.; Borner, A. Chem. Eur. J. 1998, 4, 769.
(g) Yonehara, K.; Hashizume, T.; Mori, K.; Ohe, K.;
Uemura, S. J. Org. Chem. 1999, 64, 5593. (h) Yonehara,
K.; Ohe, K.; Uemura, S. J. Org. Chem. 1999, 64, 9381.
(i) Goedheijt, M. S.; Hanson, B. E.; Reek, J. N. H.; Kamer,
Anal. Calcd for C17H20Cl2NO3P: C, 52.59; H, 5.19; N, 3.61. Found:
C, 52.56; H, 5.15; N, 3.57.
Synthesis 2009, No. 11, 1909–1915 © Thieme Stuttgart · New York

PAPER
P. C. J.; Van Leeuwen, P. W. N. M. J. Am. Chem. Soc. 2000,
Kabacknik–Fields Reaction in Aqueous Media
1915
(15) (a) Mu, X. J.; Lei, M. Y.; Zou, J. P.; Zhang, W. Tetrahedron
Lett. 2006, 47, 1125. (b) Xia, M.; Lu, Y. D. Ultrason.
Sonochem. 2006, 235. (c) Zahouily, M.; Elmakssoudi, A.;
Mezdar, A.; Rayadh, A.; Sebti, S. Catal. Commun. 2007, 8,
225. (d) Mitragotri, S. D.; Pore, D. M.; Desai, U. V.;
Wadgaonkar, P. P. Catal. Commun. 2008, 9, 1822. (e) Wu,
J.; Sun, W.; Sun, X.; Xia, H. G. Green Chem. 2006, 8, 365.
(f) Akiyama, T.; Sanada, M.; Fuchibe, K. Synlett 2003,
1463. (g) Kaboudin, B.; Sorbiun, M. Tetrahedron Lett.
2007, 48, 9015. (h) Kaboudin, B. Chem. Lett. 2001, 880.
(i) Kaboudin, B.; Saadati, F. Synthesis 2004, 1249.
(16) (a) Sobhani, S.; Tashrifi, Z. Synth. Commun. 2009, 39, 120.
(b) Sobhani, S.; Safaei, E.; Asadi, M.; Jalili, F.
122, 1650.
(8) (a) Iranpoor, N.; Firouzabadi, H.; Shekarrize, M. Org.
Biomol. Chem. 2003, 1, 724. (b) Firouzabadi, H.; Iranpoor,
N.; Amani, K. Green Chem. 2001, 3, 131. (c) Firouzabadi,
H.; Iranpoor, N.; Garzan, A. Adv. Synth. Catal. 2005, 347,
1925. (d) Firouzabadi, H.; Iranpoor, N.; Jafari, A. A. Adv.
Synth. Catal. 2005, 347, 655.
(9) Kafarski, P.; Lejezak, B. Phosphorus Sulfur Silicon Relat.
Elem. 1991, 63, 193.
(10) (a) Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J.
M. J. Med. Chem. 1989, 32, 1652. (b) Giannousis, P. P.;
Bartlett, P. A. J. Med. Chem. 1987, 30, 1603.
(11) Hirschmann, R.; Smith, A. B. III; Taylor, C. M.; Benkovic,
P. A.; Taylor, S. D.; Yager, K. M.; Sprengler, P. A.;
Venkovic, S. J. Science 1994, 265, 234.
(12) (a) Baylis, E. K.; Campell, C. D.; Dingwall, J. G. J. Chem.
Soc., Perkin Trans. 1 1984, 1, 2845. (b) Atheron, F. R.;
Hassal, C. H.; Lambert, R. W. J. Med. Chem. 1986, 29, 29.
(13) (a) Laschat, S.; Kunz, H. Synthesis 1992, 90. (b) Genet, J.
P.; Yziel, J.; Port, M.; Touzin, A. M.; Roland, S.;
Thorimbert, S.; Tanier, S. Tetrahedron Lett. 1992, 33, 77.
(14) Qian, C.; Huang, T. J. Org. Chem. 1998, 63, 4125.
J. Organomet. Chem. 2008, 693, 3313. (c) Sobhani, S.;
Safaei, E.; Asadi, M.; Jalili, F.; Tashrifi, Z. J. Porphyrins
Phthalocyanines 2008, 12, 849. (d) Sobhani, S.; Tashrifi, Z.
Heteroat. Chem. 2009, 20, 109.
(17) (a) Jönsson, B.; Lindman, B.; Holmberg, K.; Kronberg, B.
Surfactants and Polymers in Aqueous Solution; Wiley:
Chichester, 1998, 37 and 45. (b) Rosen, M. J. Surfactants
and Interfacial Phenomena; Wiley: New York, 1989, 122–
132.
Synthesis 2009, No. 11, 1909–1915 © Thieme Stuttgart · New York