A facile synthesis of aminomethylene bisphosphonates catalyzed by ytterbium perfluorooctanoate under ionic liquid condition

Article abstract of DOI:10.1016/j.jfluchem.2011.10.005

Three-component reactions of amines, triethylorthoformate and diethyl phosphite are efficiently catalyzed by ytterbium perfluorooctanoate [Yb(PFO)₃] in 1-butyl-3-methylimidazolium chloride ([bmim][Cl]) ionic liquid, giving the corresponding aminomethylene bisphosphonates in good yields. The catalyst can be recovered and reused for several times without any significant loss of activity.

Full text of DOI:10.1016/j.jfluchem.2011.10.005

Journal of Fluorine Chemistry 135 (2012) 155–158
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
A facile synthesis of aminomethylene bisphosphonates catalyzed by ytterbium
perfluorooctanoate under ionic liquid condition
Mudumala Veera Narayana Reddy a, Jongsik Kim b, Yeon Tae Jeong a,
*
a Department of Image Science and Engineering, Pukyong National University, Busan 608-737, Republic of Korea
b Department of Chemistry, Dong-A University, Busan 604-714, Republic of Korea
A R T I C L E I N F O
A B S T R A C T
Article history:
Three-component reactions of amines, triethylorthoformate and diethyl phosphite are efficiently
catalyzed by ytterbium perfluorooctanoate [Yb(PFO)3] in 1-butyl-3-methylimidazolium chloride
([bmim][Cl]) ionic liquid, giving the corresponding aminomethylene bisphosphonates in good yields.
The catalyst can be recovered and reused for several times without any significant loss of activity.
ß 2011 Elsevier B.V. All rights reserved.
Received 28 July 2011
Received in revised form 22 September 2011
Accepted 5 October 2011
Available online 12 October 2011
Keywords:
Ytterbium perfluorooctanoate
1-Butyl-3-methylimidazolium chloride
Aminomethylene bisphosphonates
Diethyl phosphite
1. Introduction
human gd T cells [10]. Classical synthetic routes to aminomethy-
lene bisphosphonates (N-BPs) involve acid catalyzed reactions of
Ionic liquids (ILs) are rapidly becoming green alternatives to the
conventional and environmentally toxic volatile organic solvents. In
recent years, ionic liquids and Lewis acid catalysts combination has
received substantial consideration from the organic community for
their innumerable advantages over conventional multistep synthe-
sis [1]. These reactions provide instantaneous access to large
compound libraries with diverse functionalities. Sang-gi Lee and his
co-workers proved that the catalytic activities were very dependent
on the ionic liquids and the catalyst immobilized in an ionic liquid
wasreused several timeswithout any lossofactivity. Moreoverionic
liquids and Lewis acid catalysts are both atom and step economic as
they avoid time consuming costly purification processes in addition
to the increase of yield. Recently, ILs have attracted a great deal of
attention due to their high thermalstability, good conductivity, non-
volatility, non-flammability, suitable polarity, wide electrochemical
window, and recyclability [2–6].
Geminal bisphosphonates (BPs) are hydrolytically stable
analogs of naturally occurring inorganic pyrophosphates (PPs)
and constitute an important class of biologically active com-
pounds. A number of these compounds have found application in
treatment of bone diseases such as Paget’s, myeloma, bone
metastases, and osteoporosis [7]. Recently, BPs have also been
used as antiprotozoan [8,9] agents and are found to stimulate
nitriles with phosphorous acid or phosphites, condensation of
amines with triethylorthoformate and phosphites [11–16], Beck-
mann rearrangement of oximes in the presence of phosphites [17]
and reductive amination of carbonyl derivatives with amino
methyl diphosphonate [18]. However, the above-mentioned
catalysts have one or more disadvantages such as long reaction
times [12], require stoichiometric amounts of toxic catalysts [13],
give poor product yields and generate large amounts of waste [12].
It is evident from the recent literature that ytterbium perfluor-
ooctanoate [Yb(PFO)3] has invoked enormous interest as a green
and potential Lewis acid catalyst to construct carbon–carbon and
carbon–heteroatom bonds in various organic transformations such
as Doebner reaction [19], Kabachnik–Fields reaction [20] Mannich
reaction [21] and Biginelli reaction [22]. It has received consider-
able attention due to its low toxicity, cost effectiveness, air and
water compatibility, ease of handling, good reactivity, recyclable
catalyst, experimental simplicity and remarkable ability to
suppress side reactions in acid sensitive substrates.
Hence, there is a need to develop a convenient, environmentally
benignand practicably feasible method forthesynthesis of N-BPs. We
report for the first time, a simple, one-pot, practical protocol for the
synthesis of N-BPs by [Yb(PFO)3] in ionic liquid [bmim][Cl] at 100 8C.
2. Results and discussion
In this letter we report an efficient and environmentally benign
* Corresponding author. Tel.: +82 51 629 6411; fax: +82 51 629 6408.
E-mail address: ytjeong@pknu.ac.kr (Y.T. Jeong).
protocol for the synthesis of N-BPs by condensation of aromatic
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.10.005

156
M. Veera Narayana Reddy et al. / Journal of Fluorine Chemistry 135 (2012) 155–158
Table 2
Influence of the solvent on the synthesis of aminomethylene bisphosphonate.a
Entry
Solvent (2 mL)
Time (min)
Yieldb (%)
1
2
Water
20
20
20
20
20
20
20
20
20
20
20
30
30
20
25
20
50
55
62
90
PEG
3
CH3CN
4
CH3COCH3
CH3NO2
CHCl3
5
Scheme 1. Synthesis of aminomethylene bisphosphonates catalyzed by [Yb(PFO)3]
6
in [bmim][Cl].
7
CH3CH2OH
DMF
8
9
Toluene
[bmim][Cl]
10
a
Reaction of p-bromoaniline (1 mmol), diethyl phosphite (2 mmol) and
triethylorthoformate (1 mmol) using 10 mol% [Yb(PFO)3] at 100 8C.
amines, diethylphosphite and triethylorthoformate catalyzed by
[Yb(PFO)3] in ionic liquid [bmim][Cl] at 100 8C (Scheme 1). The
products were obtained in high yields by a simple work-up.
Initially, we investigated the condensation reaction of p-bromoani-
line, diethyl phosphite and triethylorthoformate using different
catalysts at 100 8C, and the results are listed in Table 1. It was found
that [Yb(PFO)3] showed better catalytic activity among these
catalysts. Most excitingly, when [Yb(PFO)3] was used, the reaction
proceeded very smoothly and gave the product 3a in 90% yield
(Table 1, entry 9). Moreover, we found that the yields were
obviously affected by the amount of [Yb(PFO)3] loaded. When
1 mol%, 5 mol%, 10 mol%, and 15 mol% of [Yb(PFO)3] were used, the
yields were 35%, 75%, 90%, and 91%, respectively (Table 1, entries
9–12). Therefore, 10 mol% of [Yb(PFO)3] was sufficient and
excessive amount of catalyst did not increase the yields
significantly (Table 1, entries 9). The catalytic activity of the
recycled [Yb(PFO)3] was also examined. [Yb(PFO)3] could be reused
three times for the reaction without noticeable loss of activity
(Table 1, entry 9).
b
Isolated yield.
chloroform afforded low yields (Table 2, entries 1–6). The use of
solvents such as ethanol, DMF, and toluene could improve the
yields (Table 2, entries 8–10). Especially, the reaction could be
carried out under solvent-free condition and gave moderate yield
(Table 2, entry 7). Finally, when [bmim][Cl] was used, the yield
increased to 90% (Table 2, entry 11) better than any other solvents
examined here. The result substantiates our hypothesis that the
[Yb(PFO)3] catalyzed synthesis of N-BPs would not only be faster
but would also result in higher yields in ionic liquids as compared
to other conventional solvents. The above results showed that
[Yb(PFO)3] was essential in the reaction, and the best results were
obtained when the reaction was carried out with 10 mol% of
[Yb(PFO)3] in [bmim][Cl] at 100 8C (Table 1, entry 9).
The reaction of various aromatic/heteroaromatic amines (1a–o)
with diethyl phosphite (2) and triethylorthoformate in the
presence of the optimum quantity of [Yb(PFO)3] under [bmim][Cl]
conditions at 100 8C resulted in the formation of the N-BPs (3a–o)
(Table 3). Here, we have carried out the similar reaction with
various aromatic/heteroaromatic amines containing electron
donating or electron withdrawing functional groups at different
positions but it did not showed any remarkable differences in the
yields of product and reaction time. This result provided incentive
to extend this process to various substrates. Both aryl and
heterocyclic amines worked well in this reaction to give the
corresponding N-BPs. Reasonable yields were also observed with
less-reactive heterocyclic amines (Table 3, entries n and o). In all
the cases, the reactions were completed within 15–25 min.
In order to elucidate the role of [Yb(PFO)3], a controlled reaction
was carried out using aromatic amines, diethylphosphite and
triethylorthoformate in ionic liquid without using [Yb(PFO)3]. The
reaction proceeds with low yields (40%) even after 8 h. It is to be
noted that the reaction proceeded to give 50% yields (and took
12 h) when [Yb(PFO)3] was used alone in the absence of an ionic
liquid. It is important to note that electronic factors played an
important role in this [Yb(PFO)3] mediated condensation reaction
in ionic liquid as a reaction media. In order to elucidate the role of
the solvents, various solvents were screened to evaluate the scope
and limitation of this reaction (Table 2). The results substantiates
our hypothesis that the [Yb(PFO)3] catalyzed synthesis of N-BPs
would not only be faster but would also results in higher yields in
ionic liquids as compared to other conventional solvents. The
results indicate that different solvents affected the efficiency of the
reaction. Water, PEG, acetonitrile, acetone, nitromethane and
Table 3
Synthesis of aminomethylene bisphosphonates.a
Entry
R
Product
Time (min)
Yieldb (%)
Table 1
1
2
4-Br C6H4
3a
3b
3c
3d
3e
3f
20
18
18
15
18
18
21
22
20
15
18
25
24
25
25
90
91
90
93
92
89
88
85
90
92
90
85
85
75
70
Influence of the catalyst on the synthesis of aminomethylene bisphosphonate.a
4-Cl C6H4
Entry
Catalyst (mol%)
Time (min)
Yieldb (%)
3
4-F C6H4
4
4-Me C6H4
4-NO2 C6H4
4-Iso Propyl-C6H4
4-N(CH3)2 C6H4
2-Et C6H4
1
2
FeCl3 (10)
20
20
20
20
20
20
20
20
20
20
20
20
30
5
ZnCl2 (10)
45
6
3
I2 (10)
40
7
3g
3h
3i
4
CuCl2 (10)
55
8
5
AlCl3(10)
50
9
4-Cl, 2-NO2 C6H3
2-Cl C6H4
6
p-TSA (10)
55
10
11
12
13
14
15
3j
7
Amberlyst 15 (10)
BF3ÁSiO2 (10)
[Yb(PFO)3](10)
[Yb(PFO)3] (1)
[Yb(PFO)3] (5)
[Yb(PFO)3](15)
60
2-Me C6H4
1-Naphthyl
PhNH C6H4
2-Pyridyl
3k
3l
8
70
9c
10
11
12
90, 88, 85
3m
3n
3o
35
75
91
2-Thiazolyl
a
Reaction of p-bromoaniline (1 mmol), diethyl phosphite (2 mmol) and
triethylorthoformate (1 mmol) using 10 mol% [Yb(PFO)3] in [bmim][Cl] (2 mL) at
100 8C.
a
Reaction of p-bromoaniline (1 mmol), diethyl phosphite (2 mmol) and
triethylorthoformate (1 mmol) in [bmim][Cl] (2 mL) at 100 8C.
b
Isolated yield.
b
Isolated yield.
c
Catalyst was reused three times.

M. Veera Narayana Reddy et al. / Journal of Fluorine Chemistry 135 (2012) 155–158
157
3. Conclusion
118.2, 114.9, 63.5 (dd, J = 28.2, 5.5 Hz), 51.5 (t, J = 144.4 Hz), 16.2
(dd, J = 24.2, 6.4 Hz); 31P NMR (161.7 MHz, DMSO-d6)
: 20.2.
d
In conclusion, an efficient three component one-pot synthesis
of
a
variety of N-BPs is accomplished using [Yb(PFO)3] in
4.2.4. Tetraethyl (p-tolylamino) methylenebisphosphonate (3d)
White solid; Mp: 70–72 8C [14]. 1H NMR (400 MHz, DMSO-d6)
[bmim][Cl] at 100 8C. Reusable, eco-friendly, inexpensive, efficient
catalyst, short reaction times, high yields and easy workup are the
advantages of this protocol. This method serves as an alternative
procedure for an efficient synthesis of N-BPs.
d
: 1.14 (t, J = 6.8 Hz, 6H), 1.30 (t, J = 6.8 Hz, 6H), 2.2 (s, 3H), 3.75–
3.85 (m, 2H), 3.90–4.03 (m, 2H), 4.09–4.19 (m, 4H), 4.65 (dt,
J = 21.5, 10.0 Hz, 1H), 4.95 (d, J =10.2 Hz, 1H), 6.70 (d, J = 8.2 Hz,
2H), 6.89 (d, J = 4.5 Hz, 2H); 13C NMR (100 MHz, DMSO-d6)
d: 143.4,
128.2, 124.5, 113.9, 63.5 (dd, J = 28.2, 5.0 Hz), 52.2 (t, J = 141.4 Hz),
4. Experimental
20.5, 17.1 (dd, J = 5.4, 30.2 Hz); 31P NMR (161.7 MHz, DMSO-d6)
d:
20.5.
4.1. Method and apparatus
4.2.5. Tetraethyl (4-nitrophenylamino) methylenebisphosphonate
Chemicals were purchased from Aldrich and Alfaaesar Chemical
Companies. NMR spectra were recorded in ppm in DMSO-d6 on a
Jeol JNM ECP 400 NMR instrument using TMS as internal standard.
Mass spectra were recorded on a Jeol JMS-700 mass spectrometer.
The ionic liquid [bmim][Cl] and [Yb(PFO)3] were prepared
according to procedures from the literature [21,23].
(3e)
Yellow solid; Mp: 205–207 8C [16]. 1H NMR (400 MHz, DMSO-
: 1.10 (t, J = 7.0 Hz, 6H), 1.16 (t, J = 7.0 6H), 3.85–4.01 (m, 8H),
d6)
d
4.88 (dt, J = 21.5, 10.5 Hz, 1H), 5.20 (d, J = 10.2 Hz, 1H), 7.08 (d,
J = 9.2 Hz, 2H), 7.90 (d, J = 9.2 Hz, 2H); 13C NMR (100 MHz, DMSO-
d6)
J = 145.1 Hz), 16.7 (dd, J = 28.9, 5.5 Hz); 31P NMR (161.7 MHz,
DMSO-d6) : 18.2.
d: 154.5, 135.4 126.0, 112.8, 63.3 (dd, 28.5, 7.2 Hz), 48.4 (t,
4.2. Synthesis of tetraethyl (4-bromophenylamino)
d
methylenebisphosphonate (3a)
4.2.6. Tetraethyl (4-isopropylphenylamino)
A mixture of p-bromolaniline (1a, 1 mmol), diethyl phosphite
(2, 2 mmol), triethylorthoformate (1 mmol), [bmim][Cl] (2 mL)
was well stirred with [Yb(PFO)3] (10 mol%) at 100 8C for
appropriate time (Table 3). When the reaction was completed as
indicated by TLC, methylene chloride (5 mL) was added. The
catalyst was filtered and washed with methylene chloride (5 mL).
The filtrate was washed with water. The combined organic layer
was dried over anhydrous Na2SO4, filtered. The filtrate was
evaporated under reduced pressure. The resulting product was
purified by column chromatography on silica gel (60–120 mesh,
ethylacetate/hexane, 1:2) to afford pure product 3a. The filter
residue, which was the catalyst, was dried under vacuum and
reused in the next reaction. This procedure was applied
successfully for the preparation of other compounds.
methylenebisphosphonate (3f)
Colorless oil. IR (KBr) (
n
max cmÀ1): 3390 (NH), 1244 (P55O), 746
: 1.09 (t, J = 7.0 Hz,
(P–Caliphatic). 1H NMR (400 MHz, DMSO-d6)
d
6H), 1.19 (d, J = 5.6, Hz, 6H), 1.30 (t, J = 6.8 Hz, 6H), 2.91–2.98 (m,
1H), 3.86–3.96 (m, 4H), 4.05–4.19 (m, 4H), 4.65 (dt, J = 21.5,
10.5 Hz, 1H), 5.95 (d, J = 10.2 Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H),
7.34(dd, J = 2.2, 10.9 Hz, 2H); 13C NMR (100 MHz, DMSO-d6)
d:
138.2, 118.3, 127.6, 132.6, 63.5 (dd, J = 30.2, 7.6 Hz), 47.7 (t,
J = 142.4 Hz), 33.7, 23.8, 16.3 (dd, J = 28.2, 5.6 Hz); 31P NMR
(161.7 MHz, DMSO-d6)
18H33NO6P2: C, 51.30; H, 7.89; N, 3.32. Found: C, 51.25; H, 7.83; N,
3.18.
d
: 20.5; MS: 421 (Mꢀ+); Anal. calcd for
C
4.2.7. Tetraethyl (4-(dimethylamino)phenylamino)
methylenebisphosphonate (3g)
4.2.1. Tetraethyl (4-bromophenylamino) methylenebisphosphonate
(3a)
Colorless oil. IR (KBr) (
n
max cmÀ1): 3290 (NH), 1240 (P55O), 740
: 1.08 (t, J = 7.0 Hz,
(P–Caliphatic). 1H NMR (400 MHz, DMSO-d6)
d
White solid; Mp: 137–139 8C [14]. 1H NMR (400 MHz, DMSO-
6H), 1.28 (t, J = 6.8 Hz, 6H), 2.84 (s, 6H), 3.70–3.74 (m, 2H), 3.80–
3.92 (m, 2H), 3.98–4.12 (m, 4H), 4.85 (dt, J = 21.5, 10.5 Hz, 1H), 5.20
(d, J = 10.2 Hz, 1H), 6.55 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 7.2 Hz, 2H);
d6)
4H), 4.19–4.05 (m, 4H), 4.65 (dt, J = 21.5, 10.5 Hz, 1H), 5.95 (d,
J = 10.2 Hz, 1H), 6.75 (d, J = 8.4 Hz, 2H) 7.19 (d, J = 8.0 Hz, 2H); 13
NMR (100 MHz, DMSO-d6) : 145.5, 132.2, 117.2, 108.5, 63.5 (dd,
J = 30.5, 7.6 Hz), 50.7 (t, J = 141.4 Hz), 16.3 (dd, J = 28.2, 5.6 Hz); 31
NMR (161.7 MHz, DMSO-d6) : 20.5.
d: 1.09 (t, J = 7.0 Hz, 6H), 1.30 (t, J = 6.8 Hz, 6H), 3.96–3.86 (m,
C
13C NMR (100 MHz, DMSO-d6)
d
: 140.2, 116.3, 120.6, 63.0 (dd,
J = 29.2, 7.0 Hz), 48.5 (t, J = 144.0 Hz), 42.8, 16.3 (dd, J = 25.5,
5.6 Hz); 31P NMR (161.7 MHz, DMSO-d6) : 18.5; MS: 422 (Mꢀ+);
d
P
d
d
Anal. calcd for C17H32N2O6P2: C, 48.34; H, 7.64; N, 6.63. Found: C,
48.29; H, 7.60; N, 6.59.
4.2.2. Tetraethyl (4-chlorophenylamino) methylenebisphosphonate
(3b)
4.2.8. Tetraethyl (2-ethylphenylamino) methylenebisphosphonate
White solid; Mp: 134–136 8C [14]. 1H NMR (400 MHz, DMSO-
: 1.09 (t, J = 7.2 Hz, 6H), 1.25 (t, J = 7.2 Hz, 6H), 3.85–4.05 (m,
(3h)
d6)
d
Colorless oil [14]. 1H NMR (400 MHz, DMSO-d6)
d: 1.09 (t,
8H), 4.80 (dt, J = 22.5, 10.5 Hz, 1H), 5.2 (d, J = 9.5 Hz, 1H), 6.25 (dd,
J = 2.2, 10.2 Hz, 2H) 7.10 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz,
J = 7.0 Hz, 6H), 1.20 (t, J = 7.0 Hz, 3H), 1.30 (t, J = 6.8 Hz, 6H), 2.41–
2.49 (q, 2H), 3.75–4.09 (m, 8H), 4.35 (d, J = 10.2 Hz, 1H), 4.95 (dt,
J = 21.5, 10.5 Hz, 1H), 7.60–7.10 (m, 4H); 13C NMR (100 MHz,
DMSO-d6)
50.2 (t, J = 144.4 Hz), 16.4 (dd, J = 24.2, 5.4 Hz); 31P NMR
(161.7 MHz, DMSO-d6) : 19.2.
d: 147.5, 128.2, 119.2, 114.9, 63.5 (dd, J = 28.2, 5.5 Hz),
DMSO-d6)
d: 143.4, 128.2, 127.9, 126.5, 118.9, 112.0 62.5 (dd,
d
J = 28.2, 5.5 Hz), 50.2 (t, J = 144.4 Hz), 24.2, 16.2 (dd, J = 24.2,
5.1 Hz), 14.5; 31P NMR (161.7 MHz, DMSO-d6)
d: 18.2.
4.2.3. Tetraethyl (4-fluorophenylamino) methylenebisphosphonate
(3c)
4.2.9. Tetraethyl (4-chloro-2-nitrophenylamino)
White solid; Mp: 60–62 8C [15]. 1H NMR (400 MHz, DMSO-d6)
methylenebisphosphonate (3i)
d
: 1.11 (t, J = 7.0 Hz, 6H), 1.23 (t, J = 7.0 Hz, 6H), 3.75–3.85 (m, 2H),
Colorless oil [14]. 1H NMR (400 MHz, DMSO-d6)
d: 1.08 (t,
3.90–4.01 (m, 2H), 4.05–4.20 (m, 4H) 4.90 (dt, J = 22.5, 10.1 Hz,
1H), 5.50 (d, J = 9.5 Hz, 1H), 6.35 (dd, J = 2.2, 10.2 Hz, 2H), 6.80 (d,
J = 6.9 Hz, 6H), 1.29 (t, J = 6.9 Hz, 6H), 3.80–4.10 (m, 8H), 4.60 (dt,
J = 20.5, 9.5 Hz, 1H), 5.5 (d, J = 10.5 Hz, 1H), 7.53 (d, J = 8.2 Hz, 1H),
7.58 (d, J = 7.2 Hz, 1H), 8.10 (d, J = 2.5 Hz, 1H); 13C NMR (100 MHz,
J = 9.2 Hz, 2H); 13C NMR (100 MHz, DMSO-d6)
d: 150.2, 143.5,

158
M. Veera Narayana Reddy et al. / Journal of Fluorine Chemistry 135 (2012) 155–158
DMSO-d6)
d
: 143.5, 136.2, 132.5, 125.0, 119.9, 117.5, 64.5 (dd,
4.2.15. Tetraethyl (thiazol-2-ylamino) methylenebisphosphonate
(3o)
Colorless oil [15]. 1H NMR (400 MHz, DMSO-d6)
d: 1.10 (t,
J = 28.2, 5.5 Hz), 48.2 (t, J = 144.4 Hz), 16.0 (dd, J = 30.2, 5.4, Hz); 31
P
NMR (161.7 MHz, DMSO-d6)
d: 17.5.
J = 6.9 Hz, 6H), 1.29 (t, J = 6.9 Hz, 6H), 3.94–3.84 (m, 4H), 4.19–3.99
(m, 4H), 4.55 (dt, J = 22.5, 10.5 Hz, 1H), 5.25 (d, J = 10.2 Hz, 1H),
6.40 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.0 Hz, 1H); 13C NMR (100 MHz,
4.2.10. Tetraethyl (2-chlorophenylamino) methylenebisphosphonate
(3j)
Colorless oil [15]. 1H NMR (400 MHz, DMSO-d6)
d
: 1.11 (t,
J = 7.2 Hz, 6H), 1.30 (t, J = 7.2 Hz, 6H), 3.70–4.02 (m, 8H), 4.65 (dt,
J = 21.5, 10.5 Hz, 1H), 4.75 (d, J = 9.5 Hz, 1H), 6.40–7.05 (m, 4H); 13
NMR (100 MHz, DMSO-d6) : 142.5, 128.2, 127.5, 123.0, 119.2,
114.9, 63.2 (dd, J = 28.2, 6.5, Hz), 48.5 (t, J = 144.4 Hz), 16.4 (dd,
J = 27.2, 5.4 Hz); 31P NMR (161.7 MHz, DMSO-d6)
: 18.5.
DMSO-d6)
J = 145.7 Hz), 16.3 (dd, J = 23.0, 5.5 Hz); 31P NMR (161.7 MHz,
DMSO-d6) : 19.2.
d: 160.2, 136.5, 108.1, 63.0 (dd, J = 30.0, 7.2 Hz), 50.6 (d,
C
d
d
Acknowledgement
d
4.2.11. Tetraethyl (o-tolylamino) methylenebisphosphonate (3k)
Colorless oil [15]. 1H NMR (400 MHz, DMSO-d6)
: 1.05 (t,
This research work was supported by the grant from second of
BK21 Program.
d
J = 7.0 Hz, 6H), 1.20 (t, J = 7.0 Hz, 6H), 2.2 (s, 3H), 3.85–4.09 (m, 8H),
4.55 (dt, J = 20.5, 10.5 Hz, 1H), 5.95 (d, J = 9.5 Hz, 1H), 6.42–7.05 (m,
4H); 13C NMR (100 MHz, DMSO-d6)
d: 143.2, 128.5, 126.5, 122.0,
References
118.2, 114.2, 62.5 (dd, J = 28.2, 5.5, Hz), 49.5 (t, J = 140.4 Hz), 19.8,
15.9 (dd, J = 25.2, 5.4 Hz); 31P NMR (161.7 MHz, DMSO-d6)
d: 18.5.
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4.2.12. Tetraethyl (naphthalene-1-ylamino)
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White solid; Mp: 62–64 8C [14]. 1H NMR (400 MHz, DMSO-d6)
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d
4.35 (d, J = 9.2 Hz, 1H), 5.10 (dt, J = 21.5, 10.5 Hz, 1H), 7.01–8.05 (m,
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d
126.1, 125.0, 122.9, 120.5, 118.9, 108.0 62.5 (dd, J = 28.2, 5.5 Hz),
49.5 (t, J = 145.4 Hz), 16.7 (dd, J = 28.2, 6.2 Hz); 31P NMR
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4.2.13. Tetraethyl (4-(phenylamino)phenylamino)
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White solid; Mp: 82–84 8C [14]. 1H NMR (400 MHz, DMSO-d6)
d
: 1.09 (t, J = 7.0 Hz, 6H), 1.30 (t, J = 7.0 Hz, 6H), 3.85–4.09 (m, 8H),
4.58 (dt, J = 22.5, 10.9 Hz, 1H), 5.10 (d, J = 10.8 Hz, 1H), 6.66 (t,
J = 7.2 Hz, 1H), 6.77–7.05 (m, 6H), 7.12 (d, J = 8.2 Hz, 2H); 13C NMR
(100 MHz, DMSO-d6)
113.2, 63.5 (dd, J = 32.5, 7.2 Hz), 49.5 (t, J = 145.4 Hz), 16.0 (dd,
J = 24.5, 5.4 Hz); 31P NMR (161.7 MHz, DMSO-d6)
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d: 141.3, 133.0, 128.9, 120.5, 118.9, 113.9,
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d
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4.2.14. Tetraethyl (pyridine-2-ylamino) methylenebisphosphonate
(3n)
Colorless oil [15]. 1H NMR (400 MHz, DMSO-d6)
d: 1.17 (t,
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J = 6.9 Hz, 6H), 1.28 (t, J = 6.9 Hz, 6H), 3.94–3.84 (m, 2H), 4.19–3.99
(m, 6H), 4.75 (dt, J = 21.5, 10.5 Hz, 1H), 5.37 (d, J = 10.2 Hz, 1H),
6.76 (d, J = 8.8 Hz, 1H), 7.23 (t, J = 6.2 Hz, 1H), 7.48 (dd, J = 8.8,
1.0 Hz, 1H), 8.60 (dd, J = 5.8, 1.4 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6)
7.0 Hz), 50.6 (t, J = 142.7 Hz), 16.4 (dd, J = 23.0, 5.5 Hz); 31P NMR
(161.7 MHz, DMSO-d6) : 21.1.
d: 155.1, 149.3, 136.6, 112.8, 108.1, 63.5 (dd, J = 30.0,
d