An eco-friendly procedure for the efficient synthesis of dialkyl α-aminophosphonates in aqueous media

Article abstract of DOI:10.1016/j.jorganchem.2008.07.037

A new, convenient and high yielding procedure for the preparation of diethyl α-aminophosphonates in water by one-pot reaction of aldehydes, amines, tri/dialkyl phosphites in the presence of a low catalytic amount of [Cu(3,4-tmtppa)](MeSO₄)₄ (0.16 mol%) as a highly stable and re-usable catalyst is described.

Full text of DOI:10.1016/j.jorganchem.2008.07.037

Journal of Organometallic Chemistry 693 (2008) 3313–3317
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Communication
An eco-friendly procedure for the efficient synthesis of dialkyl
-aminophosphonates in aqueous media
a
a,*
b
c
a
Sara Sobhani , Elham Safaei , Mozaffar Asadi , Fariba Jalili
a
Department of Chemistry, College of Sciences, Birjand University, Birjand 414, Iran
Institute of Advanced Studies for Basic Sciences (IASBS), Zanjan 45195, Iran
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 May 2008
Received in revised form 28 July 2008
Accepted 29 July 2008
Available online 5 August 2008
A new, convenient and high yielding procedure for the preparation of diethyl
water by one-pot reaction of aldehydes, amines, tri/dialkyl phosphites in the presence of a low catalytic
a-aminophosphonates in
amount of [Cu(3,4-tmtppa)](MeSO
4
)
4
(0.16 mol%) as a highly stable and re-usable catalyst is described.
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
a-Aminophosphonates
Aldehydes
Amines
Aqueous media
1
. Introduction
and academic chemists, organic solvents are still used instead of
water for mainly two reasons. First, most organic substances are
insoluble in water and as a result, water does not act as a reason-
able reaction medium. Second, many reaction substrates, reagents
and catalysts are decomposed or deactivated in water. Therefore,
efforts to carry out organic reactions in water pose an important
challenge in the area of reaction design.
The synthesis of a-aminophosphonates which are considered as
analogues of amino acids has been a focus of considerable atten-
tion in synthetic organic chemistry as well as in medicinal chemis-
try [1–4]. The addition of phosphorous nucleophiles to imines is a
general reported synthetic method for the preparation of
phosphonates. This reaction is usually catalyzed by Lewis acids
such as SnCl , SnCl , ZnCl and MgBr . However, these reactions
can not proceed in one-pot from a carbonyl compound, an amine
and a phosphite. Generation of water during the course of the reac-
tion can decompose or deactivate these Lewis acids [5,6]. This
drawback has been overcome by some recent methods using lan-
thanide triflates/magnesium sulfate [7], InCl
ZrCl [10], Sc(DS) [11], 40 [12], BiNO
Mg(ClO [14,15] and b-cyclodextrine [16]. However, these meth-
ods involve either long reaction times, low yields of the products,
required stoichiometric amount of reagents, use of additives or
expensive catalysts.
One of the fundamental challenges and ultimate goals in organ-
ic synthesis is to perform the reactions in water [17,18]. Water is
cheap, safe and reduces the use of harmful organic solvents. There-
fore, it leads to the development of environmentally friendly
chemical processes [19]. Although, today’s environmental con-
sciousness imposes the use of water as a solvent on both industrial
a-amino-
Metallophthalocyanines (Mpc), which are structurally similar to
metal porphyrins, are easily accessible, more stable to degradation
and cost effective than porphyrins. They have been extensively
used as efficient catalysts in a variety of organic reactions [20–
26]. Tetrapyridinoporphyrazines (tppa) are heterocyclic phthalocy-
anine (pc) derivatives in which benzene rings are replaced with
electron-withdrawing pyridine rings. The presence of pyridine
rings in these compounds not only increases the reactivity of tppa
compared with pc, but also allows the facile quaternarization pro-
2
4
2
2
3
[8], TaCl
5
2
–SiO [9],
4
3
3
H PW12
O
3
2
ꢀ 5H O [13],
4 2
)
0
00
000
cesses. The N,N ,N ,N -tetramethylated quaternized form of tetra-
pyridinoporphyrazine can be prepared easily by its reaction with
dimethyl sulfate in dimethyl formamide [27]. The resulting tetra-
methyl-tetra-3,4-pyridinoporphyrazinato copper (II) methyl sul-
4 4
fate [Cu(3,4-tmtppa)](MeSO ) (1) (Fig. 1) is a water soluble
compound and has considerable low solubility in common organic
solvents. Unlike metallophthalocyanine, the reports on catalytic
activity of metallotetrapyridinoporphyrazine in organic reactions
are rare in the literature [28–30].
In continuation of our work on the development of new meth-
ods for the preparation of diethyl
a-functionalized phosphonates
*
Corresponding author. Tel.: +98 561 2502008; fax: +98 561 2502009.
E-mail addresses: ssobhani@birjand.ac.ir, sobhanisara@yahoo.com (S. Sobhani).
[31–36], we have already reported one-pot synthesis of diethyl
0
022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.07.037

3
314
S. Sobhani et al. / Journal of Organometallic Chemistry 693 (2008) 3313–3317
6
–10, 16). Acid-sensitive aldehydes, such as furan-2-carbaldehyde,
Me
thiophene-2-carbaldehyde, and cinnamaldehyde underwent
smooth reactions without any decomposition or polymerization
under the present reaction conditions. The coupling reaction of
n-butyraldehyde as an aliphatic aldehyde with aniline and triethyl
phosphite gave the corresponding product in high yields (Table 1,
entry 14). Naphthalene-2-carbaldehyde as a polynuclear aromatic
aldehyde also reacted with triethyl phosphite to give the desired
compound 14 in high yield. Difunctional aminophosphonates 16
and 17 were also prepared successfully by the presented method
in 90% and 91% yields (Table 1, entries 17,18). In these transforma-
tions, turnover number (TON = mole of the product/mole of cata-
lyst) is in the range of 562–612, which indicates the high
MeSO4 +N
-
N
N
N
N
Me
N+
MeSO4-
Cu
N
N
N+
MeSO4-
Me
N
N
efficiency of [Cu(3,4-tmtppa)](MeSO
wide range of -aminophosphonates. It should be noted that no
competitive side reactions such as the formation of -hydrox-
4 4
) for the preparation of a
a
a
yphosphonates were observed in these transformations. We have
also studied the reaction of ketones with aniline and triethyl phos-
phite under the same reaction conditions. However, the results
were not as positive as those presented above.
To show the effect of the catalyst, one-pot reaction of benzalde-
hyde, aniline and triethyl phosphite was examined in the absence
of the catalyst. However, this reaction remained incomplete and
only 10% of the desired product 2 was obtained after 24 h.
N+ MeSO4-
Me
4 4
Fig. 1. [Cu(3,4-tmtppa)](MeSO ) (1).
a
-aminophosphonates catalyzed by metal triflates under solvent-
After performing the preparation reaction of diethyl
ophosphonate (2) under the conditions described in Table 1, the
reaction mixture was washed with CH Cl . The separated aqueous
a-amin-
free conditions [35].
2
2
2
. Results and discussion
layer containing the catalyst was re-used for a consecutive run un-
der the same reaction conditions. The average isolated yield of 2 for
five consecutive runs was 95.2%, which clearly demonstrates the
practical reusability of this catalyst as an aqueous solution
(Fig. 2). In order to find out the yields of the catalyst recovered,
the reusability test was repeated and in each run, the catalyst
was isolated from the aqueous layer by evaporation of the solvent
(Fig. 2). The average isolated yield of the catalyst 1 for five consec-
utive runs was 97.6%. This reusability demonstrates the high sta-
In this paper, we report the successful application of [Cu(3,4-
tmtppa)](MeSO for the preparation of various types of dialkyl
-aminophosphonates from the coupling reaction of aldehydes,
4 4
)
a
amines, tri/dialkyl phosphites in water.
Initially, the coupling reaction of benzaldehyde, aniline and tri-
ethylphosphite in water with different catalytic amounts of
[
Cu(3,4-tmtppa)](MeSO
have investigated in order to optimize the reaction conditions.
The best yield of the corresponding diethyl -aminophosphonate
was obtained in the presence of 0.16 mol% of [Cu(3,4-tmtppa)]-
MeSO and at 80 °C. Then, using optimized reaction conditions,
4 4
) and at different reaction temperatures
4 4
bility and turnover of [Cu(3,4-tmtppa)](MeSO ) (1) under the
employed conditions. It is worth to note that the recyclability test
was stopped after five runs.
a
(
4
)
4
In order to show the unique behavior of [Cu(3,4-tmtppa)](Me-
the one-pot coupling reaction of a series of aldehydes and amines
4 4
SO ) for the preparation of a-aminophosphonates, we studied
with different nucleophilic phosphorus reagents using [Cu(3,4-
tmtppa)](MeSO ) as a catalyst were examined (Scheme 1). The re-
4 4
sults of these studies are presented in Table 1.
the one-pot reaction of benzaldehyde, aniline and triethylphosph-
ite in the presence of a catalytic amount of Cu-phthalocyanine tet-
rasulfate (0.16 mol%) as a water soluble phthalocyanine under the
same reaction conditions. The results showed lower yield of the
product with a longer reaction time (85%, 6 h). We have also inves-
tigated the reusability of Cu-phthalocyanine for the preparation of
diethyl a-aminophosphonate (2) by the presented method. It was
found that the reaction did not work well in the presence of recy-
cled catalyst and the starting material remained intact.
As shown in Table 1, the catalytic one-pot reaction of benzalde-
hyde and aniline proceeded well with different nucleophilic phos-
phorus reagents (Table 1, entries 1–5). These results demonstrate
that both the yields and the reaction times are relatively indepen-
dent of nucleophilic phosphorus compounds. Substituted benzal-
dehyde with electron-donating and electron-withdrawing groups
underwent coupling reaction with different substituted anilines/
benzyl amine and triethyl phosphite and gave the corresponding
In conclusion, we have found that [Cu(3,4-tmtppa)](MeSO
can be used as a new, re-usable and efficient catalyst for the prep-
aration of a variety of -aminophosphonates by one-pot reactions
4 4
)
diethyl
a-aminophosphonates in 90–98% yields (Table 1, entries
a
P(OR3)
O
R1
3
[
Cu(3,4-tmtppa)](MeSO4)4
R1
P(OR3)
2
2
O
R NH2
or
(
0.16 mol%)
H
NHR2
O
H O, 80°C
2
3
HP(OR )
90-98%
R =aryl, alkyl, allyl, heteroaryl
2
1
2
3
R =aryl
R =Et, Me, iso-Pr
Scheme 1.

S. Sobhani et al. / Journal of Organometallic Chemistry 693 (2008) 3313–3317
3315
Table 1
One-pot synthesis of dialkyl
a
-aminophosphonates from aldehydes mediated by [Cu(3,4-tmtppa)](MeSO
4
)
4
in water at 80 °C
P-Nucleophile Product
P(OEt)
Entry
Aldehyde
Amine
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
C
C
C
C
C
6
6
6
6
6
H
H
H
H
H
5
5
5
5
5
CHO
CHO
CHO
CHO
CHO
C
C
C
C
C
C
C
C
6
6
6
6
6
6
6
6
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
NH
NH
NH
NH
NH
NH
NH
NH
2
2
2
2
2
2
2
2
3
2
0.5
1
0.5
0.75
1
3
0.5
1
1
2
1
1.5
2
96
90
95
91
93
90
95
98
97
95
90
98
91
96
91
95
90
91
HP(O)(OEt)
P(OMe)
P(O-iso-Pr)
HP(O)(O-iso-Pr)
2
2
3
4
3
3
2
4
4-(MeO)-C
4-Cl-C CHO
2,6-Cl CHO
C
C
Thiophene-2-carbaldehyde
Furan-2-carbaldehyde
PhCH@CHCHO
6
H
4
CHO
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
P(OEt)
3
3
3
3
3
3
3
3
3
3
3
3
3
5
6
7
8
6
H
4
-C
2 6
H
3
6
H
H
5
CHO
CHO
4-Me-C
4-Cl-C
6
H
4
NH
2
0
1
2
3
4
5
6
7
8
6
5
6
H
4
NH
2
9
C
6
C
6
C
6
C
6
C
6
C
6
C
6
H
5
H
5
H
5
H
5
H
5
H
5
H
5
NH
NH
NH
NH
NH
2
10
11
12
13
14
15
16
17
2
2
2
2
CH
Naphthalene-2-carbaldehyde
CHO
Terephethaldehyde
CHO
3
(CH
2
)
2
CHO
1
2
1
2
C
H
6 5
CH
NH
2
NH
2
b
c
2
C
H
6 5
1,4-diaminobenzene
2
a
Yields refer to those of pure isolated products characterized by spectral data and elemental analysis.
Conditions: aniline (2 equiv.), triethyl phosphite (2 equiv.).
Conditions: benzaldehyde (2 equiv.), triethyl phosphite (2 equiv.).
b
c
solution of [Cu(3,4-tmtppa)](MeSO
20 mL). The resulting mixture was heated in an oil bath at 80 °C
and stirred for an appropriate time (Table 1). Water (20 mL) was
added to the cooled reaction mixture and extracted with CH Cl
3 ꢁ 20 mL). The combined organic extracts was washed with
SO and filtered. Pure
product 2 was isolated by preparative plate chromatography
eluted with n-hexane:EtOAc (1:1). Combined aqueous layers con-
taining the catalyst was concentrated to appropriate volume
4 4
) (0.018 g, 1.6 mmol) in water
Time Yield of 2
Yield of 1
(
1
40
20
1
2
2
100
(
8
0
water (2 ꢁ 10 mL), separated, dried over Na
2
4
6
0
4
0
0
2
(
20 mL) and re-used for the preparation of diethyl a-amino-
0
phosphonate (2) following the above procedure.
1
2
3
4
5
Fig. 2. Reusability of [Cu(3,4-tmtppa)](MeSO
of diethyl -aminophosphonate (2).
)
4 4
(1) as a catalyst for the preparation
3.3. Spectral data and elemental analysis of the products
a
3
.3.1. Diethyl (phenyl)-N-(phenyl)aminomethylphosphonate (2)
1
2
of aldehydes, amines and tri/dialkyl phosphates in water. This
reaction system not only provides a novel method for the synthesis
3 2 3
H NMR (CDCl , TMS): d 1.11 (t, 3H, JH,H = 7.1 Hz, OCH CH ),
2
1.28 (t, 3H, J = 7.1 Hz, OCH CH ), 3.59–3.69 (m, 1H, OCH CH ),
H,H
2
3
2
3
of biologically important
the applicability of [Cu(3,4-tmtppa)](MeSO
a
-aminophosphonates, but also extends
in organic synthesis
2 3 2 3
3.88–3.95 (m, 1H, OCH CH ), 4.07–4.16 (m, 2H, OCH CH ), 4.75
2
4
)
4
(d, 1H, JP,H = 26.4 Hz, CH), 4.79 (bs, 1H, NH), 6.59 (d, 2H,
2
2
2
3
2
in water which leads to environmentally friendly chemical
processes. This property combined with ease of recovery and
catalyst reusability makes this method an economic, benign and
waste-free chemical process for the synthesis of dialkyl
aminophosphonates.
6 5 6 5
JH,H = 7.9 Hz, C H ), 6.68 (t, 1H, JH,H = 7.3 Hz, C H ), 7.10 (t, 2H,
JH,H = 8.0 Hz, C H ), 7.25–7.35 (m, 3H, C H ), 7.47 (d, 2H,
6
5
6
5
13
JH,H = 7.4 Hz, C H ) ppm;
6
5
C NMR (CDCl , TMS): d 16.6 (d,
3
3
a
-
2 3 2 3
JC,P = 5.8 Hz, OCH CH ), 16.8 (d, JC,P = 5.8 Hz, OCH CH ), 56.4 (d,
1J = 150.4 Hz, CH), 63.7 (d, 2J = 7.0 Hz, OCH CH ), 114.2,
C,P
C,P
2
3
1
(
18.8, 128.2–129.6, 136.3, 146.6–146.8 (C
6
H
5
) ppm; IR: 3305
NH) cm ; MS (70 eV), m/e: 319 (M ), 182 [MꢂP(O)(OEt) ]. Anal.
Calc. for C17 P: C, 63.94; H, 6.94. Found: C, 63.92; H, 6.92%.
ꢂ1
+
2
3
. Experimental
.1. Materials and physical measurements
Chemicals were purchased from Merck and Fluka Chemical
H22NO
3
3
3
.3.2. Dimethyl (phenyl)-N-(phenyl)aminomethylphosphonate (3)
1
2
H NMR (CDCl
3
, TMS): d 3.40 (d, 3H, JP,H = 10.0 Hz, OCH
(d, 3H, JP,H = 10.0 Hz, OCH ), 4.66–4.79 (m, 2H, CH, NH), 6.51–6.63
(m, 3H, C ), 7.00–7.07 (m, 2H, C ), 7.19–7.31 (m, 3H, C ),
7.39–7.42 (m, 2H, C ) ppm; C NMR (CDCl , TMS): d 52.78 (d,
C,P = 151.5 Hz, CH), 112.83,
117.51, 126.72, 126.81, 127.02, 127.69, 128.17, 134.53 (C
3
), 3.69
2
Companies. All of the products were identified by their physical
and spectral data. IR spectra were run on a Perkin–Elmer 780
instrument. NMR spectra were recorded on a Bruker Avance DPX-
3
6
H
5
6
H
5
6 5
H
1
3
6
H
5
3
2
1
2
50. Mass spectra were recorded on a Shimadzu GCMS-QP5050A.
J
C,P = 7.1 Hz, OCH
3
), 54.62 (d,
J
The purity of the products and the progress of the reactions were
accomplished by TLC on silica-gel polygram SILG/UV254 plates.
6 5
H )
ꢂ1
+
ppm; IR: 3296 (NH) cm ; MS (70 eV), m/e: 291 (M ), 154
MꢂP(O)(OEt) ]. Anal. Calc. for C15 P: C, 61.85; H, 6.23.
Found: C, 61.83; H, 6.21%.
[
2
H18NO
3
3.2. Typical procedure for the synthesis of diethyl
a-aminophosphonate (2)
3
.3.3. Di-iso-propyl (phenyl)-N-(phenyl)aminomethylphosphonate (4)
1
Benzaldehyde (1.06 g, 10 mmol), aniline (0.931 g, 10 mmol) and
H NMR (CDCl , TMS): d 0.83–1.09 (m, 3H, OCH(CH ) ), 1.16–
3
3 2
triethyl phosphite (1.66 g, 10 mmol) were added to the stirring
3 2
1.26 (m, 9H, OCH(CH ) ), 4.36–4.40 (m, 2H, OCH(CH3)2),

3
316
S. Sobhani et al. / Journal of Organometallic Chemistry 693 (2008) 3313–3317
ꢂ1
4
.55–4.67 (m, 2H, CH, NH), 6.50–6.63 (m, 5H, C
H,H = 7.5 Hz, C H ), 7.19–7.27 (m, 1H, C H
6 5 6 5
6
H
5
), 7.02 (t, 2H,
), 7.39 (d, 2H,
, TMS): d 23.20 (d,
136.4, 144.2–144.5 (C
6
H
5
, C
(70 eV), m/e: 333 (M ), 196 [Mꢂdiethyl(phenyl)-N-(phenyl)amino-
methylphosphonate P(O)(OEt) ]. Anal. Calc. for C18 P: C,
64.85; H, 7.26. Found: C, 64.82; H, 7.24%.
6 4
H ) ppm; IR: 3303 (NH) cm ; MS
2
+
J
J
J
2
2
13
H,H = 7.4 Hz, C
6
H
5
) ppm; C NMR (CDCl
3
2
H24NO
3
2
C,P = 5.8 Hz, OCH(CH
3
)
2
), 23.77 (d,
C,P = 151.8 Hz, CH), 71.88 (d,
2.47 (d, 2JC,P = 7.6 Hz, OCH(CH
27.96, 128.04, 128.39, 129.12, 136.24, 146.43, 146.66 (C
J
C,P = 5.8 Hz, OCH(CH
JC,P = 7.6 Hz, OCH(CH
3
)
)
2
),
),
1
2
5
7
1
6.48 (d,
J
3
2
3 2
) ), 113.78, 118.20, 127.69,
3
.3.8. Diethyl (phenyl)-N-(4-chlorophenyl)aminomethylphosphonate
H )
6 5
(9)
ꢂ1
+
ppm; IR: 3308 (NH) cm ; MS (70 eV), m/e: 347 (M ), 210
MꢂP(O)(OEt) ]. Anal. Calc. for C19 P: C, 65.69; H, 7.54.
Found: C, 65.65; H, 7.51%.
1H NMR (CDCl
3
, TMS): d 0.99–1.03 (m, 3H, OCH
), 3.45–3.70 (m, 1H, OCH CH ), 3.80–4.00 (m, 1H,
), 4.02–4.04 (m, 3H, OCH CH NH), 4.62 (d, 1H,
P,H = 24.1 Hz, CH), 6.41–6.45 (m, 2H, C , C ), 6.93–6.98 (m,
H, C , C ), 7.21–7.26 (m, 3H, C , C ), 7.34–7.38 (m, 2H,
, C ) ppm; C NMR (CDCl , TMS): d 15.15 (d, JP,C = 5.8 Hz,
CH P,C = 5.8 Hz, OCH CH ), 55.14 (d,
P,C = 150.9 Hz, CH), 62.19–62.44 (m, OCH CH ), 113.97, 122.02,
26.73–127.08, 127.63–127.98, 134.39, 143.76, 143.99 (C
2 3
CH ), 1.18–1.24
[
2
H26NO
3
(
m, 3H, OCH
CH
J
2
CH
3
2
3
OCH
2
3
2
3
,
2
H
6 5
6 4
H
3.3.4. Diethyl (4-methoxyphenyl)-N-(phenyl)
2
C
6
H
5
6
H
4
6
H
5
6 4
H
aminomethylphosphonate (5)
13
3
H
6 5
6
H
4
3
1
H NMR (CDCl
m, 3H, OCH CH
.06 (m, 4H, OCH
H, C , C ), 6.77–6.81 (m, 2H, C
, C ), 7.29–7.31 (m, 2H, C , C
C,P = 5.8 Hz, OCH CH
), 55.7 (d, 1JC,P = 152.1 Hz, CH), 55.61 (OCH
3
, TMS): d 1.02–1.08, (m, 3H, OCH
), 3.70 (s, 3H, OCH ), 3.63–3.69, 3.84–3.89, 4.01–
CH ), 4.58–4.67 (m, 2H, CH, NH), 6.50–6.63 (m,
, C ), 7.00–7.03 (m, 2H,
) ppm; C NMR (CDCl
), 16.8 (d, 3
C,P=5.8 Hz,
), 63.5
2
CH
3
), 1.18–1.22
3
OCH
J
2
3
), 15.40 (d,
J
2
3
(
2
3
3
1
2
3
4
3
C
2
3
1
C
3
5
6 5
H ,
H
4
6
H
5
6
H
4
6
H
5
ꢂ1
+
6
6
4
H ) ppm; IR: 3287 (NH) cm ; MS (70 eV): m/e = 355 [M +2],
13
H
4
6
H
5
6
H
4
6
H
5
3
,
+
6
53 [M ], 216 [MꢂP(O)(OEt)
2 3
]. Anal. Calc. for C17H21ClNO P: C,
3
TMS): d 16.7 (d,
OCH CH
OCH CH
J
2
3
J
7.71; H, 5.98. Found: C, 57.69; H, 5.95%.
2
3
3
(
2
3
), 114.3–114.4, 118.7, 129.3–129.5 (C
6
H
5
, C
6
4
H ) ppm;
+
3
.3.9. Diethyl (2-thienyl)-N-(phenyl)aminomethylphosphonate (10)
ꢂ1
IR: 3303 (NH) cm
MꢂP(O)(OEt)
Found: C, 61.85; H, 6.90%.
;
MS (70 eV), m/e: 349 (M ), 212
1
H NMR (CDCl
3
, TMS): d 0.78–0.85 (m, 3H, OCH
), 3.82–4.11 (m, 4H, OCH CH ), 4.5 (bs, 1H, NH),
P,H = 23.65 Hz, OCH CH ), 6.68–6.70 (m, 3H, C
S), 6.89–6.91 (m, 1H, C , C S), 7.04–7.15 (m, 4H, C
, TMS): d 16.26 (d,
P,C = 5.8 Hz, OCH CH ), 52.08 (d,
P,C = 7.0 Hz, OCH CH ), 63.61 (d,
), 113.97, 118.93, 123.99, 125.25, 126.14,
27.07, 129.22, 139.86, 146.11 (C , C S) ppm; IR: 3291 (NH)
cm ; MS (70 eV): m/e = 325 [M ], 188 [MꢂP(O)(OEt) ]. Anal. Calc.
for C15 PS: C, 55.37; H, 6.20. Found: C, 55.35; H, 6.17%.
2 3
CH ), 1.10–1.24
[
2 4
]. Anal. Calc. for C18H24NO P: C, 61.88; H, 6.92.
(
m, 3H, OCH CH
2
3
2
3
2
4
C
C
.97 (d, 1H,
J
2
3
6
H
H
5
,
,
4
H
H
3
6
H
5
4 3
H
6
5
3.3.5. Diethyl (4-cholorophenyl)-N-(phenyl)
13
3
4
3
S) ppm; C NMR (CDCl
3
JP,C = 5.8 Hz,
aminomethylphosphonate (6)
3
OCH
2
CH
3
), 16.43 (d,
J
2
3
1
, TMS): d 1.09 (t, 3H, 2
.21 (t, 3H, JH,H = 7.1 Hz, OCH CH ), 3.69–4.09 (m, 4H, OCH
.60–4.70 (m, 2H, CH, NH), 6.48 (d, 2H, JH,H = 7.8 Hz, C
H NMR (CDCl
3
J
H,H = 7.1 Hz, OCH
2
CH
CH
3
3
5
),
),
),
1
2
J
P,C = 158.2 Hz, CH), 63.43 (d,
J
2
3
2
1
4
6
C
2
3
2
2JP,C = 7.0 Hz, OCH
2
CH
3
2
H
6 4
6
, C H
1
6
H
5
4 3
H
2
), 7.03 (t, 2H, 2
, C
.63 (t, 1H,
J
H,H = 7.3 Hz, C
6
H
4
, C
6
H
5
J
H,H = 7.8 Hz,
6 5
H ), 7.32–7.36 (m,
TMS):
ꢂ1
+
2
2
6
H
4
6
, C H
5
), 7.23 (d, 2H,
), ppm; 3C NMR (CDCl
CH C,P = 5.8 Hz, OCH
), 16.8 (d, 3
C,P = 150.5 Hz, CH), 63.7–63.9 (OCH CH
, C
J
H,H = 8.4 Hz, C
6
H
4
H20NO
3
1
2
H,
C H
6 4
,
C
6
H
5
3
,
d
16.6 (d,
3
J
C,P = 5.8 Hz, OCH
2
3
J
2
CH
3
), 55.9 (d,
3
.3.10. Diethyl (2-furyl)-N-(phenyl)aminomethylphosphonate (11)
1
J
2
3
), 114.2, 119.1, 129.2–
) ppm; IR: 3299
1
H NMR (CDCl
m, 4H, OCH CH
P,H = 22.5 Hz, CH), 6.32–6.38 (m, 2H, C
m, 3H, C O, C ), 7.12–7.38 (m, 2H, C
H, C O, C ) ppm;
C,P = 5.7 Hz, OCH CH ), 16.4 (d,
C,P = 159.5 Hz, CH), 63.3 (d, 2JC,P=7.0 Hz, OCH
3
2 3
, TMS): d 1.18–1.36 (m, 6H, OCH CH ), 3.85–4.21
), 4.52 (bs, 1H, NH), 4.67 (dd, 1H, 2JH,H = 7.0 Hz,
3
1
29.6, 134.1, 135.0, 146.3–146.5 (C
6
H
5
6 4
H
(
2
ꢂ1
+
(
[
NH) cm
MꢂP(O)(OEt)
;
MS (70 eV), m/e: 353 (M ), 355 (M+2), 216
]. Anal. Calc. for C17 21ClNO P: C, 57.71; H, 5.98.
2
J
H
4 3
O, C ), 6.65–6.77
O, C H ), 8.20 (s,
, TMS): d 16.30 (d,
C,P = 5.7 Hz, OCH CH ), 50.3 (d,
CH ), 63.5 (d,
H
6 5
2
H
3
(
4
H
3
6
H
5
4
H
3
6 5
Found: C, 57.69; H, 5.95%.
1
3
1
4
H
3
6
H
5
C NMR (CDCl
3
3
3
J
J
2
3
J
2
3
3.3.6. Diethyl (2,6-dichlorophenyl)-N-
1
2
3
(
phenyl)aminomethylphosphonate (7)
2JC,P = 7.0 Hz, OCH
), 108.8, 110.8, 114.0, 118.9, 129.2, 142.5,
) ppm; IR: 3298 (NH) cm ; MS (70 eV), m/e:
2
CH
3
1
H NMR (CDCl
m, 3H, OCH CH ), 3.81–3.84 (m, 1H, OCH
CH ), 4.10–4.19 (m, 2H, OCH CH ), 5.40 (t, 1H, NH), 5.77 (dd,
P,H = 28.6 Hz), 6.56–6.66 (m, 3H, C , C ),
, TMS):
3
, TMS): d 1.02–1.07 (m, 3H, OCH
2 3
CH ), 1.24–1.29
ꢂ1
1
3
5
49.4 (C
4
H
3
O, C
09 (M ), 172 [MꢂP(O)(OEt)
8.25; H, 6.52. Found: C, 58.23; H, 6.50%.
6
H
5
(
2
3
2
CH ), 3.94–4.01 (m, 1H,
3
+
2
4
]. Anal. Calc. for C15H20NO P: C,
OCH
2
3
2
3
3
2
1
7
1
5
6
1
H,
J
H,H = 9.95 Hz,
J
H
6 5
6 3
H
6
H
5
, C
6 3 3
H
) ppm; d 1 C NMR (CDCl
), 16.46 (d, JP,C = 5.8 Hz, OCH
P,C = 157.9 Hz, CH), 63.07 (d,
3
.01–7.27 (m, 5H, C
6.11 (d, JP,C = 5.8 Hz, OCH
3
3
3.3.11. Diethyl 3-phenyl-1-(phenylamino)allylphosphonate (12)
H NMR (CDCl , TMS): d 1.26–1.33 (m, 6H, OCH CH ), 4.10–4.23
3 2 3
2 3
(m, 5H, OCH CH , NH), 4.47 (dd, 1H, JH,H = 6.0 Hz, JP,H = 27.5 Hz,
CH), 6.24–6.30 (m, 1H, CH@CH), 6.68–6.77 (m, 4H, C H , CH@CH),
6 5
7.14–7.37 (m, 7H, C H ) ppm; C NMR (CDCl , TMS): d 22.9–23.1
(OCH CH ), 60.5 (d, JC,P=153.3 Hz, CH), 69.5 (d, JC,P = 7.0 Hz,
2
CH
3
2
CH
CH
3
),
),
1
1
2
3.14 (d,
J
J
P,C = 6.8 Hz, OCH
2
3
2
2
3.39 (d, 2JP,C = 6.8 Hz, OCH
CH
29.26, 129.30, 130.47, 130.52, 145.61, 145.86 (C
2
3
), 113.28, 113.51, 118.71, 128.34,
, C ) ppm;
6
H
5
6 3
H
1
3
ꢂ1
+
+
IR: 3322 (NH) cm ; MS (70 eV): m/e = 391 [M +4], 389 [M +2],
3
5
6
5
1
3
2
+
87 [M ], 250 [MꢂP(O)(OEt)
2
]. Anal. Calc. for C17
H
20Cl
2
NO
3
P: C,
2
3
OCH
2
CH
3
), 70.0 (d, 2JC,P = 7.0 Hz, OCH
2
CH
3
), 120.3, 124.9–139.6
2.59; H, 5.19. Found: C, 52.56; H, 5.15%.
ꢂ1
+
(
[
C
6
H
5
) ppm; IR: 3297 (NH) cm ; MS (70 eV), m/e: 345 (M ), 208
MꢂP(O)(OEt)
2 3
]. Anal. Calc. for C19H24NO P: C, 66.07; H, 7.00.
3.3.7. Diethyl (phenyl)-N-(4-methylphenyl)aminomethylphosphonate
Found: C, 66.00; H, 6.68%.
(8)
1
, TMS): d 1.15 (t, 3H, 2
H,H = 7.0 Hz, OCH CH ), 2.21 (s, 3H, CH
CH ), 3.92–4.02 (m, 1H, OCH CH ), 4.11–4.20 (m,
), 4.72–4.82 (m, 2H, CH, NH), 6.55 (d, 2H,
H NMR (CDCl
3
J
H,H = 7.0 Hz, OCH
2 3
CH ),
2
1
(
.31 (t, 3H,
m, 1H, OCH
H, OCH CH
H,H = 8.2 Hz, C
.29–7.38 (m, 3H, C
J
2
3
3
), 3.70–3.76
3.3.12. Diethyl (n-propyl)-N-(phenyl)aminomethylphosphonate (13)
1
2
H NMR (CDCl
1.24 (m, 6H, OCH
(m, 2H, NH, CH), 3.94–4.09 (m, 4H, OCH
3
, TMS): d 0.84 (t, 3H,
CH ), 1.50–1.82 (m, 4H, (CH
CH
H,H = 7.4 Hz, C
ppm; MS (70 eV), m/e: 285 (M ), 148
P: C, 58.93; H, 8.48.
J
H,H = 7.2 Hz, CH
CH ), 3.60–3.65
), 6.58 (d, 2H,
), 7.09 (t, 2H,
3
), 1.09–
2
3
2
3
2
2
3
2
3
2
)
2
3
2
), 6.94 (d, 2H, 2
, C ), 7.48–7.51 (m, 2H, C
J
H
6 4
, C
6
H
5
JH,H = 8.1 Hz, C
6
H
4
, C
, C
C,P = 5.8 Hz, OCH CH
), 20.76 (CH
C,P = 150.4 Hz, CH), 63.6–63.7 (OCH CH ), 114.4, 128.0–130.1,
H
6 5
),
2
3
2
2
7
6
H
4
6
H
5
H
6 4
H
6 5
)
J
H,H = 8.2 Hz, C
H
6 5
), 6.65 (d, 1H,
J
6 5
H
1
3
3
2JH,H = 7.6 Hz,
[MꢂP(O)(OEt)
+
ppm; C NMR (CDCl
3
, TMS): d 16.6 (d,
J
2
3
),
C
6 5
H )
3
1
6.8 (d,
JC,P=5.8 Hz, OCH CH
2
3
3
), 56.7 (d,
2
]. Anal. Calc. for C14
H24NO
3
1
J
2
3
Found: C, 58.90; H, 8.45%.

S. Sobhani et al. / Journal of Organometallic Chemistry 693 (2008) 3313–3317
3317
3
.3.13. Diethyl (2-naphthyl)-N-(phenyl)aminomethylphosphonate
[MꢂP(O)(OEt)
2
]. Anal. Calc. for C28
Found: C, 59.93; H, 6.81%.
H
38
N
2
O
6
P
2
: C, 59.99; H, 6.83.
(14)
1
, TMS): d 1.13 (t, 3H, 2
.33 (t, 3H, JH,H = 6.8 Hz, OCH CH ), 3.63–3.75 (m, 1H, OCH
.90–4.06 (m, 1H, OCH CH ), 4.14–4.21 (m, 2H, OCH CH
.04 (m, 1H, CH), 6.66–6.75 (m, 3H, C10 , C ), 7.10–7.16 (m,
H, C10 , C ), 7.48–7.67 (m, 3H, C10 , C ), 7.85 (s, 3H,
, C ), 7.98 (s, 1H, C10 , C ) ppm; C NMR (CDCl
C,P = 5.8 Hz, OCH
), 56.7 (d, 1JC,P = 150.1 Hz, CH), 63.73 (d,
H NMR (CDCl
3
J
H,H = 6.8 Hz, OCH
2
CH
CH
3
),
),
3
1
3
5
2
C
2
3
2
3
Acknowledgments
2
3
2
3
), 4.92–
H
7
6 5
H
We are thankful to Birjand University Research Council, Insti-
tute of Advanced Studies for Basic Sciences (IASBS) and Shiraz Uni-
versity for their supports.
H
7
H
6 5
H
7
6 5
H
1
3
10
H
7
H
6 5
H
7
6
H
CH
5
3
,
3
), 16.87 (d, 3
TMS): d 16.63 (d,
OCH
OCH
1
3
6
J
2
3
J
J
C,P = 5.8 Hz,
C,P = 7.0 Hz,
3
2
CH
CH
3
2
3
), 114.30, 118.86, 126.0–129.60, 133.51–133.95, 146.63–
References
ꢂ1
46.87 (C10
H
7
, C
69 (M ), 232 [MꢂP(O)(OEt)
8.29; H, 6.50. Found: C, 68.24; H, 6.45%.
6
H
5
) ppm; IR: 3301 (NH) cm ; MS (70 ev), m/e:
+
2
]. Anal. Calc. for C21
H
24NO
3
P: C,
[1] M.C. Allen, W. Fuhrer, B. Tuck, R. Wade, J.M. Wood, J. Med. Chem. 32 (1989)
1652–1661.
[
[
2] P.P. Giannousis, P.A. Bartlett, J. Med. Chem. 30 (1987) 1603–1609.
3] P.A. Bartlett, W.B. Kezer, J. Am. Chem. Soc. 106 (1984) 4283–4285.
3
.3.14. Diethyl (phenyl)-N-(benzyl)aminomethylphosphonate (15)
[4] H. Kleszczynska, J. Sarapuk, Cell. Biol. Mol. Lett. 6 (2001) 83–91.
[5] S. Laschat, H. Kunz, Synthesis (1992) 90–95.
1
, TMS): d 1.05 (t, 2
CH ), 2.95 (brs, 1H, NH), 3.44–4.07 (m,
H NMR (CDCl
.17–1.32 (m, 3H, OCH
H, OCH CH , CH , CH), 7.19–7.34 (m, 10H, C
, TMS): d 16.63 (d,
C,P = 6.1 Hz, OCH CH ), 51.59 (d,
C,P = 153.4 Hz, CH), 63.17 (d,
C,P = 7.2 Hz, OCH CH
3
2 3
JH,H=7.0 Hz, 3H, OCH CH ),
[
6] J.P. Genet, J. Yziel, M. Port, A.M. Touzin, S. Roland, S. Thorimbert, S. Tanier,
Tetrahedron Lett. 33 (1992) 77–80.
1
7
2
3
1
3
2
3
2
C
6
H
5
6
H
5
) ppm;
), 16.82 (d,
), 59.98 (d,
), 63.34 (d,
).
MS (70 eV), m/e: 333 (M ), 196
]. Anal. Calc. for C18 P: C, 64.86; H, 7.21.
Found: C, 64.85; H, 7.15%.
C
[
7] C. Qian, T. Huang, J. Org. Chem. 63 (1998) 4125–4128.
3
NMR (CDCl
3
J
C,P = 5.8 Hz, OCH
2
CH
3
[8] B.C. Ranu, A. Hajra, U. Jana, Org. Lett. 1 (1999) 1141–1143.
[9] S. Chandrasekhar, S.J. Prakash, V. Jagadeshwar, Ch. Narsihmulu, Tetrahedron
Lett. 42 (2001) 5561–5563.
3
3
J
J
J
2
3
J
C,P = 17.5 Hz, CH
2
1
2
2
J
2 3
C,P = 6.8 Hz, CH CH
[
10] J.S. Yadav, B.V.S. Reddy, K. Sarita Raj, K. Bhaskar Reddy, A.R. Prasad, Synthesis
(2001) 2260–2277.
2
3
ꢂ1
), 127.50–129.12, 136.09, 139.72 (C
.
6
H
5
+
[11] K. Manabe, S. Kobayashi, Chem. Commun. (2000) 669–670.
IR: 3309 (NH) cm
MꢂP(O)(OEt)
[
[
12] A. Heydari, H. Hamadi, M. Pourayoubi, Catal. Commun. 8 (2007) 1224–1226.
13] A.K. Bhattacharya, T. Kaur, Synlett 5 (2007) 745–748.
[
2
H24NO
3
[14] S. Bhagat, A.K. Chakraborti, J. Org. Chem. 72 (2007) 1263–1270.
[
[
[
15] J. Wu, W. Sun, H. Xia, X. Sun, Org. Biomol. Chem. 4 (2006) 1663–1666.
16] B. Kaboudin, M. Sorbiunm, Tetrahedron Lett. 48 (2007) 9015–9017.
17] C.J. Li, T.H. Chan, Organic Reactions in Aqueous Media, John Wiley & Sons, New
York, 1997.
3.3.15. Diethyl {4-[N-(phenyl)amino-
(
(
diethoxyphosphoryl)methyl]phenyl}-N-
phenyl)aminomethylphosphonate (16)
[
[
18] P.A. Grieco (Ed.), Organic Synthesis in Water, Blackie Academic and
Professional, London, 1998.
19] P. Anastas, J.C. Warner, Green Chemistry: Theory and Practice, Oxford
University Press, Oxford, 1998.
1
H NMR (CDCl
CH ), 1.11–1.20 (m, 6H, OCH
), 3.65–3.80 (m, 2H, OCH CH
), 4.65–4.73 (m, 4H, CH, NH), 6.45–6.49 (m, 4H, C
), 6.93–6.99 (m, 4H, C ), 7.36 (s, 4H,
) ppm; C NMR (CDCl , TMS): d 15.97–16.38 (OCH CH ),
P,C = 150.8 Hz, CH), 63.13–63.35 (OCH CH ), 113.89,
, C ) ppm;
3
, TMS): d 0.84–0.92 (m, 3H, OCH
CH ), 3.30–3.55 (m, 2H,
), 3.96–4.03 (m, 4H,
),
2 3
CH ), 0.93–0.98
(
m, 3H, OCH
2
3
2
3
OCH
OCH
6
C
5
1
2
CH
CH
3
2
3
[20] B. Meunier, A. Sorokin, Acc. Chem. Res 30 (1997) 470–476.
[
21] A. Sorokin, S. De Suzzoni-Dezard, D. Poullain, J.P. Noel, B. Meunier, J. Am. Chem.
Soc. 118 (1996) 7410–7411.
2
3
6 5
H
.57–6.61 (m, 2H, C
H
6 5
6 5
H
[
22] A. Sorokin, B. Meunier, J. Chem. Soc., Chem. Commun (1994) 1799–1800.
1
3
H
4
3
2
3
[23] G. Rajagopal, S.S. Kim, S.C. George, Appl. Organometal. Chem. 21 (2007) 198–
202.
6
1
5.81 (d,
J
2
3
[
[
24] V.B. Sharma, S.L. Jain, B. Sain, Catal. Lett. 98 (2004) 141–143.
25] D. Zemin, P.J. Scammells, J. Org. Chem. 72 (2007) 9881–9885.
18.33, 128.19–129.49, 135.56, 146.07–146.30 (C
6
H
5
6 4
H
ꢂ1
+
IR: 3285 (NH) cm
MꢂP(O)(OEt)
Found: C, 59.90; H, 6.80%.
;
MS (70 eV): m/e = 560 [M ], 423
: C, 59.99; H, 6.83.
[26] A.B. Sorokin, S. Mangematin, C. Pergrale, J. Mol. Catal. A: Chem. 182–183
2002) 267–281.
(
[
2
]. Anal. Calc. for C28
H
38
N
2
O
6
P
2
[
[
[
27] T.S. Smith, J. Iivorness, H. Taylor, J.R. Pilbrow, G.R. Sinclair, J. Chem. Soc., Dalton
Trans. 7 (1983) 1391–1400.
28] B. Akhlaghinia, S. Tavakoli, M. Asadi, E. Safaei, J. Porphyr. Phthalocyan. 10
(
2006) 167–175.
29] B. Akhlaghinia, M. Asadi, E. Safaei, E. Heydarpoor, Phosphorus Sulfur Silicon
79 (2004) 2099–2104.
[30] B. Akhlaghinia, M. Asadi, E. Safaei, E. Heydarpoor, J. Porphyr. Phthalocyan. 8
2004) 1285–1288.
31] H. Firouzabadi, N. Iranpoor, S. Sobhani, Tetrahedron Lett. 43 (2002) 3653–
655.
3
.3.16. Diethyl phenyl-N-{4-[N-(phenyl)amino-
(
diethoxyphosphoryl)methyl]phenyl}aminomethylphosphonate (17)
1
1
H NMR (CDCl
m, 6H, OCH CH ), 3.45–3.59 (m, 2H, OCH
CH ), 3.95–4.04 (m, 6H, OCH CH
P,H = 23.9 Hz, CH), 6.33 (s, 4H, C ), 7.14–7.35 (m, 10H, C
3
, TMS): d 0.98–1.03 (m, 6H, OCH
CH ), 3.78–3.85 (m, 2H,
NH), 4.53 (d, 2H,
2 3
CH ), 1.14–1.22
(
(
2
3
2
3
[
OCH
2
3
2
3
,
3
2
J
6
H
4
6
H
5
)
[32] H. Firouzabadi, N. Iranpoor, S. Sobhani, Tetrahedron Lett. 43 (2002) 477–480.
[33] H. Firouzabadi, N. Iranpoor, S. Sobhani, Tetrahedron 45 (2004) 203–210.
[34] H. Firouzabadi, N. Iranpoor, S. Sobhani, S. Ghassamipour, Synthesis (2005)
1
3
3
ppm; C NMR (CDCl
3
, TMS): d 16.15 (d,
C,P = 5.9 Hz, OCH CH ), 56.96 (d,
CH ), 63.20 (d, JP,C = 6.7 Hz, OCH
2
J
C,P = 5.9 Hz, OCH
2
CH
3
),
3
1
1
6
1
6.38 (d,
3.19 (d, JP,C = 6.7 Hz, OCH
J
2
3
J
C,P = 150.5 Hz, CH),
595–599.
2
2
2
3
CH
3
),
[
35] H. Firouzabadi, N. Iranpoor, S. Sobhani, Synthesis (2004) 2692–2696.
15.39, 127.07–128.49, 135.23, 138.86–139.23 (C
6
H
5
, C
6
H
4
) ppm;
[36] H. Firouzabadi, N. Iranpoor, S. Sobhani, J. Organomet. Chem. (2004) 3197–
3202.
ꢂ1
+
IR: 3291 (NH) cm
;
MS (70 eV): m/e = 560 [M ], 423