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BF3·SiO2-catalyzed one-pot synthesis of α-aminophosphonates in ionic liquid and neat conditions
Tetrahedron Letters 52 (2011) 4764–4767
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BF3SiO2-catalyzed one-pot synthesis of a-aminophosphonates in ionic liquid and neat conditions 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
Article history: Received 2 June 2011 Revised 30 June 2011 Accepted 6 July 2011 Available online 19 July 2011 Keywords: a-Aminophosphonates 5-Amino 2,2-difluoro-1,3-benzodioxole Diethyl phosphite BF3SiO2/[bmim][HCl]
a b s t r a c t a-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 (BF3SiO2) 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. Ó 2011 Elsevier Ltd. All rights reserved.
Introduction
a-Aminophosphonates have attracted much attention owing to their biological activities. Their utilities as enzyme inhibitors, antibiotics, peptide mimics, herbicides, pharmacological agents, and many other applications are well documented.1–5 A number of synthetic methods for the preparation of a-aminophosphonates have been carried out under solvent-free conditions, such as CoCl26H2O,6 [Yb(PFO)3],7 Nano Fe3O4,8 Mg(ClO4)2,9 metal 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 abovementioned 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, BF3SiO218 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 promotion of many acid catalyzed organic reactions.19,20 At the same time, ionic liquids (ILs) have been frequently used as green alternatives to conventional solvents due to their nonvolatility, nonflammability 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 selectivity compared to commonly used volatile solvents.21,22 ⇑ Corresponding author. Tel.: +82 51 629 6411; fax: +82 51 629 6408. E-mail address: [email protected] (Y.T. Jeong). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.07.027
In addition, the ability of ILs to immobilize and recycle catalysts makes them an ideal medium for the transition-metal catalyzed oxidations.23 Hence, there is a need to develop a convenient, environmentally benign, and practicably feasible method for the synthesis of aaminophosphonates. We report for the first time, a simple, onepot, practical protocol for the synthesis of a-aminophosphonates by BF3SiO2 in ionic liquid ([bmim][HCl]) under solvent-free conditions at room temperature. Result and discussion In this Letter, we report an efficient and environmentally benign protocol for the synthesis of a-aminophosphonates (4a–o) by condensation of 5-amino 2,2-difluoro-1,3-benzodioxole (1), various aromatic aldehydes (2a–o), and diethyl phosphite (3) in the presence of catalytic amount (5 mol %) of BF3SiO2 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 BF3SiO2. 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 BF3SiO2 could efficiently catalyze this reaction and afford the desired products in high yields in relatively shorter time.
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F
O +
F
O
NH 2 (1)
BF3.SiO 2 O OEt ([bmim][HCl]) F R-CHO + H P 5-10 min OEt F RT, Neat
O R O
N H
O
OEt
(4a-o)
(3)
(2a-o)
OEt P
Scheme 1. Synthesis of a-aminophosphonate catalyzed by BF3SiO2 in [bmim][HCl].
In our attempt to optimize the experimental conditions, we studied the effect of different amounts of catalyst required for this transformation (Table 2, entries 8–12). We found that 5 mol % of BF3SiO2 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 favors side reactions and decomposition of the formed products to the corresponding aldehyde and amine. Thus, it was found that 5 mol % BF3SiO2 catalyst at room temperature in 5 min of time is an appropriate condition for BF3SiO2-catalyzed one-pot Kabachnik–Fields reaction. After optimizing the conditions, the generality of this method was examined by the reaction of several substituted aryl/heteroaryl/aliphatic aldehydes, 5-amino 2,2-difluoro-1,3-benzodioxole, and diethyl phosphite using BF3SiO2 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 shorter time and gave higher yields (Table 1). On the basis of the above results, 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, respectively, (Table 1, entries14 and 15). Compared with aromatic, heterocyclic aldehydes, aliphatic aldehydes afforded relatively lower yields of the corresponding a-aminophosphonate (Table 1). The reusability of the BF3SiO218 catalyst was also examined. After each run, the product was filtered, the solvent was evaporated, and the catalyst residue was washed with CHCl3 and reused. Treatment with CHCl3 removes tars more efficiently from the catalyst surface. For example, the reaction of p-methoxybenzaldehyde, Table 1 Synthesis of a-aminophosphonates in the presence of 5 mol % of BF3SiO2 in 1-butyl3-methylimidazolium hydrochloride [bmim][HCl] ionic liquid Entry
Aldehydes (R)
Product
Time (min)
Yielda (%)
1 2 3 4 5 6 7 8 9 10 11 12 13
4-Br C6H4 4-Cl C6H4 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
4a 4b 4c 4d 4e 4f 4g 4h 4i 4j 4k 4l 4m
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
4n
8
85
4o
10
80
N
14
15 a
CH3CH2CH2–
Isolated yield.
Table 2 Influence of the catalyst on the synthesis of a-aminophosphonate (4a–o)a Entry
Catalyst (mol %)
Time (h)
Yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12
No Cat ZnCl2 (10) ZnSO4 (10) CuCl2 (10) AlCl3(10) p-TSA (10) FeCl3 (10) BF3SiO2(2) BF3SiO2(4) BF3SiO2(5) BF3SiO2(8) BF3SiO2(10)
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
a Reaction of p-methoxybenzaldehyde (1 mmol), 5-amino 2,2-difluoro-1,3benzo-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 Entry
Solvent
Time (min)
Yieldb (%)
1 2 3 4 5
([bmim][HCl]) 1,4 Dioxane THF Acetonitrile Dichloromethane
5 180 180 110 150
97 65 65 75 60
a Reaction of p-methoxybenzaldehyde (1 mmol), 5-amino 2,2-difluoro-1,3benzo-dioxole (1 mmol), and diethyl phosphite (1 mmol) using 5 mol % BF3SiO2. b Isolated yield.
Table 4 Recyclability of BF3SiO2 Entry-6
Run 1
Run 2
Run 3
Run 4
Run 5
Yield (%)
97
95
92
90
90
5-amino 2,2-difluoro-1,3-benzodioxole, and diethyl phosphite in the presence of BF3SiO2 in ([bmim][HCl]) gave the corresponding a-aminophosphonates in 97%, 95% 92%, 90%, and 90% yields over five cycles and the results were also summarized in Table 4. These results indicate that the BF3SiO2 catalyst is highly efficient for the 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 simple and a good contribution in the field of a-aminophosphonates. Conclusion In conclusion, we have described an efficient and environmentally benign method for the synthesis of a-aminophosphonates from 5-amino 2,2-difluoro-1,3-benzodioxole, aldehydes, and diethyl phosphite using 5% BF3SiO2 in ionic liquid ([bmim][HCl]) under neat condition. The major advantages of BF3SiO2 are that it is a reusable, eco-friendly, inexpensive, and efficient catalyst. Short reaction times, high yields and easy workup are the advantages of this protocol.
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Experimental section 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 BF3SiO2 (5 mol %) were taken in a 10-mL round-bottomed 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 iso-propanol, and chloroform (85:15) to afford pure a-aminophosphonates in 97% yield. This procedure was applied successfully for the preparation of other compounds (Table 1). 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) cm 1. 1H NMR (400 MHz, CDCl3) d: 7.22 (dd, J = 11.0, 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+). 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– Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d : 7.22–7.12 (m, 2H), 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+). 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) cm 1. 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-hydroxyphenyl)methylphosphonate (4d) Solid, mp 145–147 °C. IR (KBr): m 3290 (NH), 1217 (P@O), 740 (P–Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d: 7.50 (s, 1H), 7.18
(dd, J = 10.8, 2.2 Hz, 2H), 6.76 (d, J = 8.2 Hz, 2H), 6.68 (d, 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). 13 C 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+). 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) cm 1. 1H NMR (400 MHz, CDCl3) d: 7.31 (dd, J = 10.2, 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+). Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) (4-methoxyphenyl)methylphosphonate (4f) Solid, mp 155–157 °C. IR (KBr): m 3294 (NH), 1230 (P@O), 762 (P–Caliphatic) cm 1. 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-nitrophenyl)methylphosphonate (4g) Solid, mp 126–128 °C. IR (KBr): m 3300 (NH), 1230 (P@O), 742 (P–Caliphatic) cm 1. 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-Isopropylphenyl)methylphosphonate (4h) Solid, mp 103–105 °C. IR (KBr): m 3275 (NH), 1230 (P@O), 745 (P–Caliphatic) cm 1. 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).13C NMR (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+).
M. V. Reddy et al. / Tetrahedron Letters 52 (2011) 4764–4767
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) (3-chlorophenyl)methylphosphonate (4i) Solid, mp 88–90 °C. IR (KBr): m 3290 (NH), 1232 (P@O), 744 (P– Caliphatic) cm 1. 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) (2-hydroxyphenyl)methylphosphonate (4j) Solid, mp 125–127 °C. IR (KBr): m 3275 (NH), 1220 (P@O), 742 (P–Caliphatic) cm 1. 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. Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) (3-methoxyphenyl)methylphosphonate (4k) Solid, mp 144–146 °C. IR (KBr): m 3270 (NH), 1230 (P@O), 750 (P–Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d: 7.30 (dd, J = 11.0 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. Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) (2-nitrophenyl)methylphosphonate (4l) Solid, mp 126–128 °C. IR (KBr): m 3280 (NH), 1233 (P@O), 742 (P–Caliphatic) cm 1. 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. Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)(5-chloro-2hydroxyphenyl)methylphosphonate (4m) Solid, mp 120–122 °C. IR (KBr): m 3270 (NH), 1225 (P@O), 759 (P–Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d: 8.25 (s, 1H), 7.10 (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+). 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– Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d: 8.60 (dd, J = 5.8,
4767
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+). Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) butylphosphonate (4o) Liquid, IR (KBr): m 3290 (NH), 1230 (P@O), 745 (P–Caliphatic) cm . H 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+). 1 1
Acknowledgment This research work was supported by the grant from second of BK21 Program. References and notes 1. Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1989, 32, 1652. 2. Allenberger, F.; Klare, I. J. Antimicrob. J. Chemother. 1999, 43, 211. 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. 6. Karimi-Jaberi, Z.; Hassan, Z.; Amiri, M.; Sadeghi, N. Chin. Chem. Lett. 2011, 22, 559. 7. Tang, J.; Wanga, L.; Wang, W.; Zhang, L.; Wu, S.; Mao, D. J. Fluorine Chem. 2011, 132, 102. 8. Subba Reddy, B. V.; Siva Krishna, A.; Ganesh, A. V.; Narayana Kumar, G. G. K. S. Tetrahedron Lett. 2011, 52, 1359. 9. Bhagat, S.; Chakraborti, A. K. J. Org. Chem. 2007, 72, 1263. 10. Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Synthesis 2004, 2692. 11. Ghosh, R.; Maiti, S.; Chakraborty, A.; Maiti, D. J. Mol. Catal. A: Chem. 2004, 210, 53. 12. Sun, P. P.; Hu, Z. X.; Huang, Z. H. Synth. Commun. 2004, 34, 4293. 13. Zhan, Z. P.; Li, J. P. Synth. Commun. 2005, 35, 2501. 14. Paraskar, A. S.; Sudalai, A. Arkivoc 2006, 10, 183. 15. Ambica, K. S.; Taneja, S. C.; Hundal, M. S.; Kapoor, K. K. Tetrahedron Lett. 2008, 49, 2208. 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 Chem. 2002, 4, 436; (c) Lee, S.; Lee, J. K.; Song, C. E.; Kim, D. C. Bull. Korean Chem. Soc. 2002, 23, 667; (d) Lee, S.; Park, J. H.; Kang, J.; Lee, J. K. Chem. Commun. 2001, 1698. 17. Chandrasekhar, S.; Narsihmulu, C.; Sultana, S. S.; Saritha, B.; Prakash, S. J. Synlett 2003, 505. 18. Sadeghi, B.; Mirjalili, B. F.; Hashemi, M. M. Tetrahedron Lett. 2008, 49, 2575. 19. Mirjalili, B. F.; Bamoniri, A.; Akbari, A. Tetrahedron Lett. 2008, 49, 6454. 20. Sadegi, B.; Mirjalili, B. F.; Hashememi, M. M. J. Iran. Chem. Soc. 2008, 5, 694. 21. (a) Greaves, T. L.; Drummond, C. J. Chem. Rev. 2008, 108, 206; (b) Welton, T. Chem. Rev. 1999, 99, 2071; (c) Sheldon, R. Chem. Commun. 2001, 2399. 22. (a) Haumann, M.; Riisager, A. Chem. Rev. 2008, 108, 1474; (b) Plaquevent, J. C.; Levillain, J.; Guillen, F.; Malhiac, C.; Gaumont, A. C. Chem. Rev. 2008, 108, 5035; (c) Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.; Bonacorso, H. G. Chem. Rev. 2008, 108, 2015. 23. (a) Muzart, J. Adv. Synth. Catal. 2006, 348, 275; (b) Rong, M. Z.; Liu, C.; Han, J. Y.; Wang, H. Catal. Commun. 2009, 10, 362; (c) Jiang, N.; Ragauskas, A. J. Tetrahedron Lett. 2007, 48, 273; (d) Conte, V.; Floris, B.; Galloni, P.; Silvagni, A. Adv. Synth. Catal. 2005, 347, 1341.
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BF3SiO2-catalyzed one-pot synthesis of a-aminophosphonates in ionic liquid and neat conditions 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
Article history: Received 2 June 2011 Revised 30 June 2011 Accepted 6 July 2011 Available online 19 July 2011 Keywords: a-Aminophosphonates 5-Amino 2,2-difluoro-1,3-benzodioxole Diethyl phosphite BF3SiO2/[bmim][HCl]
a b s t r a c t a-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 (BF3SiO2) 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. Ó 2011 Elsevier Ltd. All rights reserved.
Introduction
a-Aminophosphonates have attracted much attention owing to their biological activities. Their utilities as enzyme inhibitors, antibiotics, peptide mimics, herbicides, pharmacological agents, and many other applications are well documented.1–5 A number of synthetic methods for the preparation of a-aminophosphonates have been carried out under solvent-free conditions, such as CoCl26H2O,6 [Yb(PFO)3],7 Nano Fe3O4,8 Mg(ClO4)2,9 metal 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 abovementioned 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, BF3SiO218 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 promotion of many acid catalyzed organic reactions.19,20 At the same time, ionic liquids (ILs) have been frequently used as green alternatives to conventional solvents due to their nonvolatility, nonflammability 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 selectivity compared to commonly used volatile solvents.21,22 ⇑ Corresponding author. Tel.: +82 51 629 6411; fax: +82 51 629 6408. E-mail address: [email protected] (Y.T. Jeong). 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.07.027
In addition, the ability of ILs to immobilize and recycle catalysts makes them an ideal medium for the transition-metal catalyzed oxidations.23 Hence, there is a need to develop a convenient, environmentally benign, and practicably feasible method for the synthesis of aaminophosphonates. We report for the first time, a simple, onepot, practical protocol for the synthesis of a-aminophosphonates by BF3SiO2 in ionic liquid ([bmim][HCl]) under solvent-free conditions at room temperature. Result and discussion In this Letter, we report an efficient and environmentally benign protocol for the synthesis of a-aminophosphonates (4a–o) by condensation of 5-amino 2,2-difluoro-1,3-benzodioxole (1), various aromatic aldehydes (2a–o), and diethyl phosphite (3) in the presence of catalytic amount (5 mol %) of BF3SiO2 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 BF3SiO2. 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 BF3SiO2 could efficiently catalyze this reaction and afford the desired products in high yields in relatively shorter time.
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M. V. Reddy et al. / Tetrahedron Letters 52 (2011) 4764–4767
F
O +
F
O
NH 2 (1)
BF3.SiO 2 O OEt ([bmim][HCl]) F R-CHO + H P 5-10 min OEt F RT, Neat
O R O
N H
O
OEt
(4a-o)
(3)
(2a-o)
OEt P
Scheme 1. Synthesis of a-aminophosphonate catalyzed by BF3SiO2 in [bmim][HCl].
In our attempt to optimize the experimental conditions, we studied the effect of different amounts of catalyst required for this transformation (Table 2, entries 8–12). We found that 5 mol % of BF3SiO2 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 favors side reactions and decomposition of the formed products to the corresponding aldehyde and amine. Thus, it was found that 5 mol % BF3SiO2 catalyst at room temperature in 5 min of time is an appropriate condition for BF3SiO2-catalyzed one-pot Kabachnik–Fields reaction. After optimizing the conditions, the generality of this method was examined by the reaction of several substituted aryl/heteroaryl/aliphatic aldehydes, 5-amino 2,2-difluoro-1,3-benzodioxole, and diethyl phosphite using BF3SiO2 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 shorter time and gave higher yields (Table 1). On the basis of the above results, 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, respectively, (Table 1, entries14 and 15). Compared with aromatic, heterocyclic aldehydes, aliphatic aldehydes afforded relatively lower yields of the corresponding a-aminophosphonate (Table 1). The reusability of the BF3SiO218 catalyst was also examined. After each run, the product was filtered, the solvent was evaporated, and the catalyst residue was washed with CHCl3 and reused. Treatment with CHCl3 removes tars more efficiently from the catalyst surface. For example, the reaction of p-methoxybenzaldehyde, Table 1 Synthesis of a-aminophosphonates in the presence of 5 mol % of BF3SiO2 in 1-butyl3-methylimidazolium hydrochloride [bmim][HCl] ionic liquid Entry
Aldehydes (R)
Product
Time (min)
Yielda (%)
1 2 3 4 5 6 7 8 9 10 11 12 13
4-Br C6H4 4-Cl C6H4 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
4a 4b 4c 4d 4e 4f 4g 4h 4i 4j 4k 4l 4m
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
4n
8
85
4o
10
80
N
14
15 a
CH3CH2CH2–
Isolated yield.
Table 2 Influence of the catalyst on the synthesis of a-aminophosphonate (4a–o)a Entry
Catalyst (mol %)
Time (h)
Yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12
No Cat ZnCl2 (10) ZnSO4 (10) CuCl2 (10) AlCl3(10) p-TSA (10) FeCl3 (10) BF3SiO2(2) BF3SiO2(4) BF3SiO2(5) BF3SiO2(8) BF3SiO2(10)
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
a Reaction of p-methoxybenzaldehyde (1 mmol), 5-amino 2,2-difluoro-1,3benzo-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 Entry
Solvent
Time (min)
Yieldb (%)
1 2 3 4 5
([bmim][HCl]) 1,4 Dioxane THF Acetonitrile Dichloromethane
5 180 180 110 150
97 65 65 75 60
a Reaction of p-methoxybenzaldehyde (1 mmol), 5-amino 2,2-difluoro-1,3benzo-dioxole (1 mmol), and diethyl phosphite (1 mmol) using 5 mol % BF3SiO2. b Isolated yield.
Table 4 Recyclability of BF3SiO2 Entry-6
Run 1
Run 2
Run 3
Run 4
Run 5
Yield (%)
97
95
92
90
90
5-amino 2,2-difluoro-1,3-benzodioxole, and diethyl phosphite in the presence of BF3SiO2 in ([bmim][HCl]) gave the corresponding a-aminophosphonates in 97%, 95% 92%, 90%, and 90% yields over five cycles and the results were also summarized in Table 4. These results indicate that the BF3SiO2 catalyst is highly efficient for the 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 simple and a good contribution in the field of a-aminophosphonates. Conclusion In conclusion, we have described an efficient and environmentally benign method for the synthesis of a-aminophosphonates from 5-amino 2,2-difluoro-1,3-benzodioxole, aldehydes, and diethyl phosphite using 5% BF3SiO2 in ionic liquid ([bmim][HCl]) under neat condition. The major advantages of BF3SiO2 are that it is a reusable, eco-friendly, inexpensive, and efficient catalyst. Short reaction times, high yields and easy workup are the advantages of this protocol.
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Experimental section 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 BF3SiO2 (5 mol %) were taken in a 10-mL round-bottomed 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 iso-propanol, and chloroform (85:15) to afford pure a-aminophosphonates in 97% yield. This procedure was applied successfully for the preparation of other compounds (Table 1). 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) cm 1. 1H NMR (400 MHz, CDCl3) d: 7.22 (dd, J = 11.0, 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+). 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– Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d : 7.22–7.12 (m, 2H), 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+). 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) cm 1. 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-hydroxyphenyl)methylphosphonate (4d) Solid, mp 145–147 °C. IR (KBr): m 3290 (NH), 1217 (P@O), 740 (P–Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d: 7.50 (s, 1H), 7.18
(dd, J = 10.8, 2.2 Hz, 2H), 6.76 (d, J = 8.2 Hz, 2H), 6.68 (d, 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). 13 C 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+). 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) cm 1. 1H NMR (400 MHz, CDCl3) d: 7.31 (dd, J = 10.2, 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+). Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) (4-methoxyphenyl)methylphosphonate (4f) Solid, mp 155–157 °C. IR (KBr): m 3294 (NH), 1230 (P@O), 762 (P–Caliphatic) cm 1. 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-nitrophenyl)methylphosphonate (4g) Solid, mp 126–128 °C. IR (KBr): m 3300 (NH), 1230 (P@O), 742 (P–Caliphatic) cm 1. 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-Isopropylphenyl)methylphosphonate (4h) Solid, mp 103–105 °C. IR (KBr): m 3275 (NH), 1230 (P@O), 745 (P–Caliphatic) cm 1. 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).13C NMR (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+).
M. V. Reddy et al. / Tetrahedron Letters 52 (2011) 4764–4767
Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) (3-chlorophenyl)methylphosphonate (4i) Solid, mp 88–90 °C. IR (KBr): m 3290 (NH), 1232 (P@O), 744 (P– Caliphatic) cm 1. 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) (2-hydroxyphenyl)methylphosphonate (4j) Solid, mp 125–127 °C. IR (KBr): m 3275 (NH), 1220 (P@O), 742 (P–Caliphatic) cm 1. 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. Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) (3-methoxyphenyl)methylphosphonate (4k) Solid, mp 144–146 °C. IR (KBr): m 3270 (NH), 1230 (P@O), 750 (P–Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d: 7.30 (dd, J = 11.0 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. Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) (2-nitrophenyl)methylphosphonate (4l) Solid, mp 126–128 °C. IR (KBr): m 3280 (NH), 1233 (P@O), 742 (P–Caliphatic) cm 1. 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. Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino)(5-chloro-2hydroxyphenyl)methylphosphonate (4m) Solid, mp 120–122 °C. IR (KBr): m 3270 (NH), 1225 (P@O), 759 (P–Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d: 8.25 (s, 1H), 7.10 (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+). 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– Caliphatic) cm 1. 1H NMR (400 MHz, CDCl3) d: 8.60 (dd, J = 5.8,
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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+). Diethyl(2,2difluorobenzo[d][1,3]dioxol-5-ylamino) butylphosphonate (4o) Liquid, IR (KBr): m 3290 (NH), 1230 (P@O), 745 (P–Caliphatic) cm . H 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+). 1 1
Acknowledgment This research work was supported by the grant from second of BK21 Program. References and notes 1. Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1989, 32, 1652. 2. Allenberger, F.; Klare, I. J. Antimicrob. J. Chemother. 1999, 43, 211. 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. 6. Karimi-Jaberi, Z.; Hassan, Z.; Amiri, M.; Sadeghi, N. Chin. Chem. Lett. 2011, 22, 559. 7. Tang, J.; Wanga, L.; Wang, W.; Zhang, L.; Wu, S.; Mao, D. J. Fluorine Chem. 2011, 132, 102. 8. Subba Reddy, B. V.; Siva Krishna, A.; Ganesh, A. V.; Narayana Kumar, G. G. K. S. Tetrahedron Lett. 2011, 52, 1359. 9. Bhagat, S.; Chakraborti, A. K. J. Org. Chem. 2007, 72, 1263. 10. Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Synthesis 2004, 2692. 11. Ghosh, R.; Maiti, S.; Chakraborty, A.; Maiti, D. J. Mol. Catal. A: Chem. 2004, 210, 53. 12. Sun, P. P.; Hu, Z. X.; Huang, Z. H. Synth. Commun. 2004, 34, 4293. 13. Zhan, Z. P.; Li, J. P. Synth. Commun. 2005, 35, 2501. 14. Paraskar, A. S.; Sudalai, A. Arkivoc 2006, 10, 183. 15. Ambica, K. S.; Taneja, S. C.; Hundal, M. S.; Kapoor, K. K. Tetrahedron Lett. 2008, 49, 2208. 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 Chem. 2002, 4, 436; (c) Lee, S.; Lee, J. K.; Song, C. E.; Kim, D. C. Bull. Korean Chem. Soc. 2002, 23, 667; (d) Lee, S.; Park, J. H.; Kang, J.; Lee, J. K. Chem. Commun. 2001, 1698. 17. Chandrasekhar, S.; Narsihmulu, C.; Sultana, S. S.; Saritha, B.; Prakash, S. J. Synlett 2003, 505. 18. Sadeghi, B.; Mirjalili, B. F.; Hashemi, M. M. Tetrahedron Lett. 2008, 49, 2575. 19. Mirjalili, B. F.; Bamoniri, A.; Akbari, A. Tetrahedron Lett. 2008, 49, 6454. 20. Sadegi, B.; Mirjalili, B. F.; Hashememi, M. M. J. Iran. Chem. Soc. 2008, 5, 694. 21. (a) Greaves, T. L.; Drummond, C. J. Chem. Rev. 2008, 108, 206; (b) Welton, T. Chem. Rev. 1999, 99, 2071; (c) Sheldon, R. Chem. Commun. 2001, 2399. 22. (a) Haumann, M.; Riisager, A. Chem. Rev. 2008, 108, 1474; (b) Plaquevent, J. C.; Levillain, J.; Guillen, F.; Malhiac, C.; Gaumont, A. C. Chem. Rev. 2008, 108, 5035; (c) Martins, M. A. P.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.; Bonacorso, H. G. Chem. Rev. 2008, 108, 2015. 23. (a) Muzart, J. Adv. Synth. Catal. 2006, 348, 275; (b) Rong, M. Z.; Liu, C.; Han, J. Y.; Wang, H. Catal. Commun. 2009, 10, 362; (c) Jiang, N.; Ragauskas, A. J. Tetrahedron Lett. 2007, 48, 273; (d) Conte, V.; Floris, B.; Galloni, P.; Silvagni, A. Adv. Synth. Catal. 2005, 347, 1341.