BF3·SiO2-catalyzed one-pot synthesis of α-aminophosphonates in ionic liquid and neat conditions

Article abstract of DOI:10.1016/j.tetlet.2011.07.027

α-Aminophosphonates were synthesized in a simple and efficient method from the three-component condensation reaction of 5-amino 2,2-difluoro-1,3- benzodioxole, aromatic aldehydes, and diethyl phosphite by silica-supported boron trifluoride (BF₃

Full text of DOI:10.1016/j.tetlet.2011.07.027

Tetrahedron Letters 52 (2011) 4764–4767
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
BF3ÁSiO2-catalyzed one-pot synthesis of
liquid and neat conditions
a-aminophosphonates in ionic
⇑
Mudumala Veeranarayana Reddy, Someshwar D. Dindulkar, Yeon Tae Jeong
Department of Image Science and Engineering, Pukyong National University, Busan 608-737, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
a
-Aminophosphonates were synthesized in a simple and efficient method from the three-component
Received 2 June 2011
Revised 30 June 2011
Accepted 6 July 2011
Available online 19 July 2011
condensation reaction of 5-amino 2,2-difluoro-1,3-benzodioxole, aromatic aldehydes, and diethyl phos-
phite by silica-supported boron trifluoride (BF3ÁSiO2) in ionic liquid ([bmim][HCl]) under solvent-free
conditions at room temperature in good to excellent yields and short reaction times. The catalyst can
be recovered and reused for several times without any significant loss of activity. It was observed that
a homogeneous reaction medium proved beneficial for the yield of the reaction.
Keywords:
Ó 2011 Elsevier Ltd. All rights reserved.
a-Aminophosphonates
5-Amino 2,2-difluoro-1,3-benzodioxole
Diethyl phosphite
BF3ÁSiO2/[bmim][HCl]
Introduction
In addition, the ability of ILs to immobilize and recycle catalysts
makes them an ideal medium for the transition-metal catalyzed
a-Aminophosphonates have attracted much attention owing to
oxidations.23
their biological activities. Their utilities as enzyme inhibitors, anti-
biotics, peptide mimics, herbicides, pharmacological agents, and
many other applications are well documented.1–5
Hence, there is a need to develop a convenient, environmentally
benign, and practicably feasible method for the synthesis of
aminophosphonates. We report for the first time, a simple, one-
pot, practical protocol for the synthesis of -aminophosphonates
a-
A number of synthetic methods for the preparation of
a-amino-
a
phosphonates have been carried out under solvent-free conditions,
by BF3ÁSiO2 in ionic liquid ([bmim][HCl]) under solvent-free condi-
such as CoCl2Á6H2O,6 [Yb(PFO)3],7 Nano Fe3O4,8 Mg(ClO4)2,9 metal
tions at room temperature.
triflate.10 The
a-aminophosphonates have also been synthesized in
organic solvents using In(OTf)3/MgSO4,11 GaI3,12 BiCl3,13 Cu(OTf)2,14
SbCl3/Al2O3.15 Lewis acid–surfactant-combined catalyst16 and even
in the absence of solvent and catalyst.17 However, the above-
mentioned catalysts have one or more disadvantages, such as long
reaction times, moisture sensitive catalysts, require stoichiometric
amounts of toxic catalysts, give poor product yields, and generate
large amounts of waste. Silica-supported boron trifluoride,
BF3ÁSiO218 is a bench-top catalyst which is easy to handle, reusable,
cheap, readily available, eco-friendly, versatile, and enables better
accessibility of the reactants to the active sites and efficient for pro-
motion of many acid catalyzed organic reactions.19,20 At the same
time, ionic liquids (ILs) have been frequently used as green alterna-
tives to conventional solvents due to their nonvolatility, nonflam-
mability and thermal stability. Their high polarity and the ability
to solubilize both inorganic and organic compounds can result in
an enhanced rate of chemical processes and provide higher selectiv-
ity compared to commonly used volatile solvents.21,22
Result and discussion
In this Letter, we report an efficient and environmentally benign
protocol for the synthesis of a-aminophosphonates (4a–o) by con-
densation of 5-amino 2,2-difluoro-1,3-benzodioxole (1), various
aromatic aldehydes (2a–o), and diethyl phosphite (3) in the pres-
ence of catalytic amount (5 mol %) of BF3ÁSiO2 in ionic liquid
([bmim][HCl]) under solvent-free conditions at room temperature
(Scheme 1). Comparing with other organic solvents, ([bmim][HCl])
was the most effective reaction medium (Table 3, entry 1). It was
confirmed that 4 was the only product in the presence of BF3ÁSiO2.
We also screened different common Lewis acids for their ability
to catalyze the three-component Kabachnik–Fields reaction and
5-amino 2,2-difluoro-1,3-benzodioxole, p-methoxybenzaldehyde,
and diethyl phosphite were selected as models. As shown in Table
2, the common Lewis acids such as ZnCl2, ZnSO4, CuCl2, AlCl3,
p-TSA, and FeCl3 afforded the desired product but only in moderate
yield (Table 2, entries 2–7). We have re-examined this reaction and
found that BF3ÁSiO2 could efficiently catalyze this reaction and
afford the desired products in high yields in relatively shorter time.
⇑
Corresponding author. Tel.: +82 51 629 6411; fax: +82 51 629 6408.
E-mail address: ytjeong@pknu.ac.kr (Y.T. Jeong).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.027

M. V. Reddy et al. / Tetrahedron Letters 52 (2011) 4764–4767
4765
O
O
BF3.SiO2
([bmim][HCl])
O
P
O
O
F
F
F
F
OEt
OEt
R
+
R-CHO
H
+
OEt
5-10 min
RT, Neat
P
N
H
NH2
OEt
O
(3)
(4a-o)
(1)
(2a-o)
Scheme 1. Synthesis of
a
-aminophosphonate catalyzed by BF3ÁSiO2 in [bmim][HCl].
In our attempt to optimize the experimental conditions, we stud-
ied the effect of different amounts of catalyst required for this
transformation (Table 2, entries 8–12). We found that 5 mol % of
BF3ÁSiO2 was sufficient to drive the reaction to completion giving
97% product yield in 5 min at room temperature. Less amounts of
catalyst gave lower yields even after prolonged reaction time and
higher mol % quantities could not cause the obvious increase in
the product yield and decrease the reaction time. In addition,
Kabachnik–Fields reaction is very sensitive to the temperature.
The high temperature even though improves the reaction rate fa-
vors side reactions and decomposition of the formed products to
the corresponding aldehyde and amine. Thus, it was found that
5 mol % BF3ÁSiO2 catalyst at room temperature in 5 min of time is
an appropriate condition for BF3ÁSiO2-catalyzed one-pot Kabach-
nik–Fields reaction.
Table 2
Influence of the catalyst on the synthesis of
a
-aminophosphonate (4a–o)a
Entry
Catalyst (mol %)
Time (h)
Yieldb (%)
1
No Cat
6.0
3.0
3.5
3.0
3.0
2.5
2.0
5 min
5 min
5 min
5 min
5 min
50
55
50
65
60
70
70
80
85
97
97
97
2
3
4
5
ZnCl2 (10)
ZnSO4 (10)
CuCl2 (10)
AlCl3(10)
6
7
8
9
10
11
12
p-TSA (10)
FeCl3 (10)
BF3ÁSiO2(2)
BF3ÁSiO2(4)
BF3ÁSiO2(5)
BF3ÁSiO2(8)
BF3ÁSiO2(10)
a
Reaction of p-methoxybenzaldehyde (1 mmol), 5-amino 2,2-difluoro-1,3-
After optimizing the conditions, the generality of this method
was examined by the reaction of several substituted aryl/hetero-
aryl/aliphatic aldehydes, 5-amino 2,2-difluoro-1,3-benzodioxole,
and diethyl phosphite using BF3ÁSiO2 in ionic liquid ([bmim][HCl])
under neat condition, the results are shown in Table 1. In all cases,
aromatic aldehydes substituted with either electron-donating or
electron-withdrawing groups underwent the reaction smoothly
and gave the products in good yields. It could also be concluded that
the aldehydes bearing electron-withdrawing groups required short-
er time and gave higher yields (Table 1). On the basis of the above re-
sults, this process was then extended to heterocyclic and aliphatic
aldehydes. Pyridin-2-carboxaldehyde and butyraldehyde afforded
the corresponding products (4n, 4o) in 85%, and 80% yields, respec-
tively, (Table 1, entries14 and 15). Compared with aromatic, hetero-
cyclic aldehydes, aliphatic aldehydes afforded relatively lower
benzo-dioxole (1 mmol) and diethyl phosphite (1 mmol) in [bmim][HCl].
b
Isolated yield.
Table 3
Influence of the solvent on the synthesis of
a
-aminophosphonatea
Time (min)
Entry
Solvent
Yieldb (%)
1
2
3
4
5
([bmim][HCl])
1,4 Dioxane
THF
Acetonitrile
Dichloromethane
5
97
65
65
75
60
180
180
110
150
a
Reaction of p-methoxybenzaldehyde (1 mmol), 5-amino 2,2-difluoro-1,3-
benzo-dioxole (1 mmol), and diethyl phosphite (1 mmol) using 5 mol % BF3ÁSiO2.
b
Isolated yield.
yields of the corresponding a-aminophosphonate (Table 1).
18
The reusability of the BF3ÁSiO2 catalyst was also examined.
After each run, the product was filtered, the solvent was evapo-
rated, and the catalyst residue was washed with CHCl3 and reused.
Treatment with CHCl3 removes tars more efficiently from the cata-
lyst surface. For example, the reaction of p-methoxybenzaldehyde,
Table 4
Recyclability of BF3ÁSiO2
Entry-6
Run 1
97
Run 2
95
Run 3
92
Run 4
90
Run 5
90
Yield (%)
Table 1
Synthesis of
a-aminophosphonates in the presence of 5 mol % of BF3ÁSiO2 in 1-butyl-
5-amino 2,2-difluoro-1,3-benzodioxole, and diethyl phosphite in
3-methylimidazolium hydrochloride [bmim][HCl] ionic liquid
the presence of BF3ÁSiO2 in ([bmim][HCl]) gave the corresponding
Entry
Aldehydes (R)
Product
Time (min)
Yielda (%)
a-aminophosphonates in 97%, 95% 92%, 90%, and 90% yields over
1
2
3
4
5
6
7
8
4-Br C6H4
4-Cl C6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
5
6
6
5
5
5
8
6
8
8
6
5
7
94
96
97
96
97
97
92
96
90
92
95
95
92
five cycles and the results were also summarized in Table 4. These
results indicate that the BF3ÁSiO2 catalyst is highly efficient for the
4-EtO C6H4
4-OH C6H4
4-Me C6H4
4-OMe C6H4
4-NO2 C6H4
4-iso PropylC6H4
2-OHC6H4
2-NO2C6H4
3-Cl C6H4
3-OMe C6H4
5-Cl-2-OH C6H3
synthesis of
a-aminophosphonates and could avoid the necessity
of anhydrous conditions, highly expensive and toxic reagents, and
moisture sensitive Lewis acids. The developed methodology is sim-
ple and a good contribution in the field of a-aminophosphonates.
9
Conclusion
10
11
12
13
4j
4k
4l
In conclusion, we have described an efficient and environmen-
tally benign method for the synthesis of -aminophosphonates
4m
a
from 5-amino 2,2-difluoro-1,3-benzodioxole, aldehydes, and
diethyl phosphite using 5% BF3ÁSiO2 in ionic liquid ([bmim][HCl])
under neat condition. The major advantages of BF3ÁSiO2 are that
it is a reusable, eco-friendly, inexpensive, and efficient catalyst.
Short reaction times, high yields and easy workup are the advanta-
ges of this protocol.
N
14
15
4n
4o
8
85
80
CH3CH2CH2–
10
a
Isolated yield.

4766
M. V. Reddy et al. / Tetrahedron Letters 52 (2011) 4764–4767
(dd, J = 10.8, 2.2 Hz, 2H), 6.76 (d, J = 8.2 Hz, 2H), 6.68 (d,
Experimental section
J = 8.0 Hz, 1H), 6.68 (d, J = 8.0 Hz, 1H), 6.23 (dd, J = 11.2, 2.2 Hz,
1H), 5.50 (br s, 1H), 4.58 (d, J = 23.6 Hz, 1H), 4.17–3.90 (m, 3H),
3.79–3.69 (m, 1H), 1.27 (t, J = 8.0 Hz, 3H), 1.19 (t, J = 8.0 Hz, 3H).
13C NMR (100 MHz, CDCl3) d: 158.9, 144.5, 143.5, 136.3, 131.0,
129.0, 128.0, 126.8, 109.0, 107.0, 96.5, 63.3 (dd, J = 32.5, 7.5 Hz,),
55.2 (d, J = 163.4 Hz), 16.4 (dd, J = 25.6, 5.8 Hz). 31P NMR
(161.7 MHz, CDCl3) d: 22.0. MS: (m/z) 415 (M+).
Synthesis of diethyl (2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-methoxyphenyl) methylphosphonate (4f)
A mixture of p-methoxybenzaldehyde (2f, 1 mmol), 5-amino
2,2-difluoro-1,3-benzodioxole (1, 1 mmol), diethyl phosphite (3,
1 mmol), and BF3ÁSiO2 (5 mol %) were taken in a 10-mL round-bot-
tomed flask containing 1 mL of ([bmim][HCl]) was stirred at room
temperature for 5 min. The progress of the reaction was monitored
by TLC. After completion of the reaction, the mixture was washed
with chloroform and filtered to recover the catalyst. The filtrate
was evaporated, and the crude product was recrystallized from
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-methylphenyl)methylphosphonate (4e)
Solid, mp 147–149 °C. IR (KBr):
m 3295 (NH), 1228 (P@O), 742
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.31 (dd, J = 10.2,
.
iso-propanol, and chloroform (85:15) to afford pure a-aminophos-
phonates in 97% yield. This procedure was applied successfully for
the preparation of other compounds (Table 1).
2.2 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.4 Hz, 1H), 6.34
(d, J = 2.5 Hz, 1H), 6.23 (dd, J = 11.0, 2.5 Hz, 1H), 4.70 (br s, 1H),
4.61 (d, J = 24.2 Hz, 1H), 4.15–4.09 (m, 2H), 3.95–3.87 (m, 1H),
3.66–3.64 (m, 1H), 2.32 (s, 3H), 1.30 (t, J = 6.9 Hz, 3H), 1.11 (t,
J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) d: 158.9, 144.5, 143.5,
138.0, 136.4, 132.1, 129.5, 127.7, 109.8, 107.8, 96.5, 63.4 (dd,
J = 27.0, 7.1 Hz), 56.3 (d, J = 151.0 Hz), 21.2, 16.4 (dd, J = 27.8,
5.5 Hz). 31P NMR (161.7 MHz, CDCl3) d: 22.2. MS: (m/z) 413 (M+).
Characterization data
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-bromophenyl)methylphosphonate (4a)
Solid, mp 106–108 °C. IR (KBr):
m 3290 (NH), 1235 (P@O), 740
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.22 (dd, J = 11.0,
.
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-methoxyphenyl)methylphosphonate (4f)
2.2 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.4 Hz, 1H), 6.30
(d, J = 4.5 Hz, 1H), 6.20 (dd, J = 11.0 2.5 Hz, 1H), 4.78 (br s, 1H),
4.58 (d, J = 23.2 Hz, 1H), 4.10–3.90 (m, 2H), 3.85–3.77 (m, 2H),
1.27 (t, J = 6.9 Hz, 3H), 1.14 (t, J = 6.9 Hz, 3H). 13C NMR (100 MHz,
CDCl3) d: 157.9, 144.5, 143.5, 136.5, 133.7, 129.9, 125.8, 119.0,
109.8, 107.0, 96.5, 63.5 (dd, J = 27.2, 5.2 Hz), 56.5 (d, J = 152.0 Hz),
16.4 (dd, J = 24.5, 5.0 Hz). 31P NMR (161.7 MHz, CDCl3) d: 21.2.
MS: (m/z) 477 (M+).
Solid, mp 155–157 °C. IR (KBr):
m 3294 (NH), 1230 (P@O), 762
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.35 (dd, J = 10.9,
.
2.5 Hz, 2H), 6.87 (d, J = 8.4 Hz, 2H), 6.76 (d, J = 8.7 Hz, 1H), 6.35
(d, J = 2.2 Hz, 1H), 6.23 (dd, J = 11.0, 2.2 Hz, 1H), 4.90 (br s, 1H),
4.60 (d, J = 23.8 Hz, 1H), 4.15–4.10 (m, 2H), 3.96–3.90 (m, 1H),
3.78 (s, 3H), 3.72–3.60 (m, 1H), 1.30 (t, J = 6.9 Hz, 3H), 1.13 (t,
J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3) d: 159.4, 144.4, 143.6,
136.3, 134.2, 131.6, 129.0, 127.0, 114.1, 109.6, 107.7, 96.5, 63.3
(dd, J = 27.8, 7.1 Hz), 55.5 (d, J = 146.0 Hz), 55.1, 16.3 (dd, J = 24.6,
5.5 Hz). 31P NMR (161.7 MHz, CDCl3) d: 22.2. MS: (m/z) 429 (M+).
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-chlorophenyl)methylphosphonate (4b)
Solid, mp 99–101 °C. IR (KBr):
m 3295 (NH), 1230 (P@O), 740 (P–
C
aliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.22–7.12 (m, 2H),
.
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-nitrophenyl)methylphosphonate (4g)
6.92–6.84 (m, 2H), 6.70 (d, J = 8.4 Hz, 1H), 6.35 (d, J = 4.0 Hz, 1H),
6.22 (dd, J = 11.0, 2.2 Hz, 1H), 5.90 (br s, 1H), 4.64 (d, J = 23.2 Hz,
1H), 4.10–3.90 (m, 4H), 1.28 (t, J = 6.9 Hz, 3H), 1.14 (t, J = 6.9 Hz,
3H). 13C NMR (100 MHz, CDCl3) d: 158.9, 144.5, 143.6, 136.3,
131.7, 128.9, 126.8, 114.5, 109.6, 107.0, 96.5, 63.3 (dd, J = 30.5,
7.3 Hz), 56.0 (d, J = 154.0 Hz), 16.4 (dd, J = 27.8, 6.2 Hz). 31P NMR
(161.7 MHz, CDCl3) d: 19.1. MS: (m/z) 433 (M+).
Solid, mp 126–128 °C. IR (KBr):
m 3300 (NH), 1230 (P@O), 742
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 8.23 (dd, J = 11.0
.
2.2 Hz, 2H), 7.31 (d, J = 4.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 1H), 6.29
(d, J = 4.0 Hz, 1H), 6.18 (dd, J = 10.9, 2.2 Hz, 1H), 4.90 (br s, 1H),
4.62 (d, J = 24.0 Hz, 1H), 4.15–3.80 (m, 4H), 1.29 (t, J = 7.2 Hz,
3H), 1.14 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) d: 158.9,
144.5, 143.5, 136.3, 131.0, 129.0, 128.0, 126.8, 114.7, 109.0,
107.0, 96.5, 63.3 (dd, J = 30.5, 7.5 Hz), 55.2 (d, J = 163.4 Hz), 16.4
(dd, J = 24.5, 5.8 Hz). 31P NMR (161.7 MHz, CDCl3) d: 23.2. MS:
(m/z) 444 (M+).
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-ethoxyphenyl)methylphosphonate (4c)
Solid, mp 115–117 °C. IR (KBr):
m 3280 (NH), 1235 (P@O), 752
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.33 (dd, J = 10.9,
.
2.2 Hz, 2H), 6.86 (d, J = 4.0 Hz, 2H), 6.76 (d, J = 8.0 Hz, 1H), 6.34
(d, J = 4.0 Hz, 1H), 6.23 (dd, J = 10.9, 2.5 Hz, 1H), 5.20 (br, s, 1H),
4.54 (d, J = 16.0 Hz, 1H), 4.16–3.81 (m, 5H), 3.70–3.60 (m, 1H),
1.30 (t, J = 8.2 Hz, 3H), 1.28 (t, J = 8.0 Hz, 3H), 1.10 (t, J = 8.0 Hz,
3H). 13C NMR (100 MHz, CDCl3)). 13C NMR (100 MHz, CDCl3) d:
158.9, 144.5, 143.6, 136.3, 131.7, 128.9, 126.8, 114.5, 109.6,
107.0, 96.5, 63.3 (dd, J = 25.5, 5.5 Hz), 62.4, 56.0 (d, J = 152.0 Hz),
16.4 (dd, J = 23.5, 5.0 Hz,), 14.8. 31P NMR (161.7 MHz, CDCl3) d:
20.2. MS: (m/z) 443 (M+).
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-Isopropylphenyl)methylphosphonate (4h)
Solid, mp 103–105 °C. IR (KBr):
m 3275 (NH), 1230 (P@O), 745
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.35 (dd, J = 10.2,
.
2.2 Hz, 2H), 7.19 (d, J = 8.2 Hz, 2H), 6.75 (d, J = 8.4 Hz, 1H), 6.36
(d, J = 2.5 Hz, 1H), 6.25 (dd, J = 10.9, 2.2 Hz, 1H), 4.99 (br s, 1H),
4.62 (d, J = 24.1 Hz, 1H), 4.15–4.09 (m, 2H), 3.92–3.88 (m, 1H),
3.67–3.61 (m, 1H), 3.00–2.82 (m, 1H), 1.29 (t, J = 8.0 Hz, 3H), 1.21
(dd, J = 19.8, 10.8 Hz, 6H), 1.08 (t, J = 8.0 Hz, 3H).13
C NMR
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(4-hydroxyphenyl)methylphosphonate (4d)
(100 MHz, CDCl3) d: 149.5, 144.4, 143.5, 136.2, 132.2, 127.6,
126.6, 109.5, 107.7, 96.3, 63.3 (dd, J = 25.0, 6.3 Hz), 57.0 (d,
J = 152.0 Hz), 33.7, 23.8, 16.3 (dd, J = 36.5, 5.8 Hz). 31P NMR
(161.7 MHz, CDCl3) d: 22.2. MS: (m/z) 441 (M+).
Solid, mp 145–147 °C. IR (KBr):
m 3290 (NH), 1217 (P@O), 740
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.50 (s, 1H), 7.18
.

M. V. Reddy et al. / Tetrahedron Letters 52 (2011) 4764–4767
4767
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(3-chlorophenyl)methylphosphonate (4i)
1.4 Hz, 1H), 7.66–7.64 (q, 1H), 7.48 (dd, J = 8.8, 1.0 Hz 1H), 7.23
(t, J = 6.2 Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 6.48 (d, J = 2.5 Hz 1H),
6.33 (dd, J = 11.0, 2.2 Hz, 1H), 5.37 (br s, 1H), 4.88 (d, J = 21.6 Hz,
1H), 4.19–3.99 (m, 3H), 3.94–3.84 (m, 1H), 1.28 (t, J = 6.9 Hz, 3H),
1.17 (t, J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3) d: 155.1, 149.3,
144.5, 143.6, 136.9, 136.6, 123.1, 122.9, 109.8, 108.1, 96.8, 63.5
(dd, J = 30.0, 7.0 Hz), 58.6 (d, J = 151.7 Hz), 16.4 (dd, J = 23.0,
5.5 Hz). 31P NMR (161.7 MHz, CDCl3) d: 21.1. MS: (m/z) 400 (M+).
Solid, mp 88–90 °C. IR (KBr):
m 3290 (NH), 1232 (P@O), 744 (P–
C
aliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.22–7.12 (m, 2H),
.
6.92–6.84 (m, 2H), 6.76 (d, J = 8.4 Hz, 1H), 6.42 (d, J = 4.0 Hz, 1H),
6.30 (dd, J = 11.0, 2.2 Hz, 1H), 4.90 (br s, 1H), 4.92 (d, J = 23.2 Hz,
1H), 4.16–3.91 (m, 4H), 1.28 (t, J = 8.0 Hz, 3H), 1.20 (t, J = 8.0 Hz,
3H). 13C NMR (100 MHz, CDCl3) d: 149.5, 144.5, 143.6, 136.5,
135.7, 129.1, 127.1, 126.9, 108.8, 106.7, 96.6, 62.7 (dd, J = 24.5,
5.0 Hz), 55.3 (d, J = 150.0 Hz), 15.5 (dd, J = 24.5, 7.0 Hz). 31P NMR
(161.7 MHz, CDCl3) d: 21.1. MS: (m/z) 433 (M+).
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
butylphosphonate (4o)
Liquid, IR (KBr):
m
3290 (NH), 1230 (P@O), 745 (P–Caliphatic) cm
À1
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(2-hydroxyphenyl)methylphosphonate (4j)
.
1H NMR (400 MHz, CDCl3) d: 6.72 (d, J = 4.0 Hz, 1H), 6.33 (d,
J = 4.0 Hz, 1H), 6.20 (dd, J = 10.9, 2.2 Hz, 1H), 4.90 (br s, 1H), 4.86
(d, J = 22.5 Hz, 1H), 4.17–4.02 (m, 2H), 3.96–3.86 (m, 2H), 1.39–
1.30 (m, 4H), 1.28 (t, J = 8.0 Hz, 3H), 1.19 (t, J = 8.0 Hz, 3H), 0.98
(t, J = 8 Hz, 3H). 13C NMR (100 MHz, CDCl3) d: 149.9, 144.5, 143.5,
136.3, 109.5, 107.0, 96.5, 63.3 (dd, J = 28.5, 7.5 Hz), 55.2 (d,
J = 163.4 Hz), 25.2, 21.0 16.4 (dd, J = 24.5, 5.8 Hz), 14.7. 31P NMR
(161.7 MHz, CDCl3) d: 22.0. MS: (m/z) 365 (M+).
Solid, mp 125–127 °C. IR (KBr):
m 3275 (NH), 1220 (P@O), 742
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 8.10 (s, 1H),
.
7.32–7.22 (m, 4H), 6.78 (d, J = 8.0 Hz, 1H), 6.32 (d, J = 4.0 Hz, 1H),
6.19 (dd, J = 10.9, 2.2 Hz), 4.95 (br s, 1H), 4.60 (d, J = 24.4 Hz),
4.18–4.08 (m, 2H), 4.02–3.92 (m, 1H), 3.78–3.71 (m, 1H), 1.30 (t,
J = 8.0 Hz, 3H), 1.14 (t, J = 7.2 Hz, 3H). 31P NMR (161.7 MHz, CDCl3)
d: 21.0.
Acknowledgment
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(3-methoxyphenyl)methylphosphonate (4k)
This research work was supported by the grant from second of
BK21 Program.
Solid, mp 144–146 °C. IR (KBr):
m 3270 (NH), 1230 (P@O), 750
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 7.30 (dd, J = 11.0
.
References and notes
2.5 Hz, 2H), 6.92 (d, J = 8.2 Hz, 2H), 6.70 (d, J = 4.0 Hz, 1H), 6.30
(d, J = 4.0 Hz, 1H), 6.22 (dd, J = 11.0, 2.5 Hz, 1H), 5.10 (br s, 1H),
4.62 (d, J = 24.0 Hz, 1H), 4.12–4.01 (m, 2H), 3.94–3.85 (m, 1H),
3.80 (s, 3H), 3.72–3.63 (m, 1H), 1.28 (t, J = 6.9 Hz, 3H), 1.14 (t,
J = 6.9 Hz, 3H). 31P NMR (161.7 MHz, CDCl3) d: 23.2.
1. Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1989, 32,
1652.
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3. Kafarski, P.; LeJczak, B. Phosphorus, Sulfur Silicon Relat. Elem. 1991, 53, 193.
4. Natchev, I. A. Liebigs Ann. Chem. 1988, 861.
5. Chung, S. K.; Kang, D. H. Tetrahedron: Asymmetry 1996, 7, 21.
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132, 102.
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(2-nitrophenyl)methylphosphonate (4l)
8. Subba Reddy, B. V.; Siva Krishna, A.; Ganesh, A. V.; Narayana Kumar, G. G. K. S.
Tetrahedron Lett. 2011, 52, 1359.
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10. Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Synthesis 2004, 2692.
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53.
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13. Zhan, Z. P.; Li, J. P. Synth. Commun. 2005, 35, 2501.
14. Paraskar, A. S.; Sudalai, A. Arkivoc 2006, 10, 183.
Solid, mp 126–128 °C. IR (KBr):
m 3280 (NH), 1233 (P@O), 742
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 8.20 (d, J = 8.0 Hz,
.
2H), 7.50 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 7.2 Hz, 1H), 6.30 (d,
J = 4.0 Hz, 1H), 6.18 (dd, J = 11.0, 2.5 Hz, 1H), 4.25 (br s, 1H), 4.60
(d, J = 24.0 Hz, 1H), 4.10–3.80 (m, 4H), 1.26 (t, J = 8.0 Hz, 3H),
1.11 (t, J = 8.0 Hz, 3H). 31P NMR (161.7 MHz, CDCl3) d: 21.8.
15. Ambica, K. S.; Taneja, S. C.; Hundal, M. S.; Kapoor, K. K. Tetrahedron Lett. 2008,
49, 2208.
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)(5-chloro-2-
hydroxyphenyl)methylphosphonate (4m)
16. (a) Sadaphal, S. A.; Sonar, S. S.; Kategaonkar, A. H.; Shingare, M. S. Bull. Korean
Chem. Soc. 2009, 30, 1054; (b) Yadav, J. S.; Reddy, B. V. S.; Sreedhar, P. Green
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1698.
Solid, mp 120–122 °C. IR (KBr):
m 3270 (NH), 1225 (P@O), 759
(P–Caliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 8.25 (s, 1H), 7.10
.
17. Chandrasekhar, S.; Narsihmulu, C.; Sultana, S. S.; Saritha, B.; Prakash, S. J.
Synlett 2003, 505.
(s, 1H), 6.95 (d, J = 4.2 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.54 (d,
J = 4 Hz, 1H), 6.35 (d, J = 4.0 Hz, 1H), 6.15 (dd, J = 10.9, 2.2 Hz,
1H), 5.90 (br s, 1H), 4.62 (d, J = 23.8 Hz, 1H), 4.09–3.80 (m, 4H),
1.28 (t, J = 8.0 Hz, 3H), 1.19 (t, J = 8.0 Hz, 3H). 13C NMR (100 MHz,
CDCl3) d: 158.9, 144.5, 143.5, 136.3, 131.0, 129.0, 128.0, 126.8,
114.7, 109.0, 107.0, 96.5, 63.3 (dd, J = 30.4, 7.5 Hz), 55.2 (d,
J = 163.4 Hz), 16.4 (dd, J = 25.2, 5.8 Hz). 31P NMR (161.7 MHz,
CDCl3) d: 22.2. MS: (m/z) 449 (M+).
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Tetrahedron Lett. 2007, 48, 273; (d) Conte, V.; Floris, B.; Galloni, P.; Silvagni,
A. Adv. Synth. Catal. 2005, 347, 1341.
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)
(pyridine-2-yl)methylphosphonate (4n)
Solid, mp 88–90 °C. IR (KBr):
m 3280 (NH), 1229 (P@O), 749 (P–
C
aliphatic) cmÀ1 1H NMR (400 MHz, CDCl3) d: 8.60 (dd, J = 5.8,
.