A domino knoevenagel-phospha-michael reaction: One-pot synthesis of novel organophosphonates in the presence of multi-walled carbon nanotube?CO?NH(CH2)2NH-SO3H as catalyst

Article abstract of DOI:10.1080/10426507.2018.1452230

We report a one-pot method for the synthesis of various substituted 1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl phosphonate derivatives via phosphorus-carbon bond formation through domino Knoevenagel–phospha–Michael reaction. Multi-walled carbon nanotube?CO?NH(CH₂)₂NH-SO₃H was used as an acidic heterogeneous catalyst. The catalyst could be used four times without losing its catalytic activity. The structures of the products were determined by FT-IR spectra, ¹H-, ¹³C- and ³¹P- Nuclear Magnetic Resonance and elemental analysis. Recovery and reusability of catalyst, simplicity, applicability, good reaction time and good yields of products are the benefits of this work.

Full text of DOI:10.1080/10426507.2018.1452230

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
A domino Knoevenagel-phospha-Michael reaction:
one-pot synthesis of novel organophosphonates in
the presence of multi-walled carbon nanotube-CO-
NH(CH2)2NH-SO3H as catalyst
Fatemeh Homayoun & Soheila Ghassamipour
To cite this article: Fatemeh Homayoun & Soheila Ghassamipour (2018): A domino Knoevenagel-
phospha-Michael reaction: one-pot synthesis of novel organophosphonates in the presence of
multi-walled carbon nanotube-CO-NH(CH2)2NH-SO3H as catalyst, Phosphorus, Sulfur, and Silicon
and the Related Elements, DOI: 10.1080/10426507.2018.1452230
To link to this article: https://doi.org/10.1080/10426507.2018.1452230
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Publisher: Taylor & Francis
Journal: Phosphorus, Sulfur, and Silicon and the Related Elements
DOI: https://doi.org/10.1080/10426507.2018.1452230
A domino Knoevenagel-phospha-Michael reaction: one-pot synthesis of
novel organophosphonates in the presence of multi-walled carbon
nanotube-CO-NH(CH2)2NH-SO3H as catalyst
Fatemeh Homayoun, Soheila Ghassamipour*
Department of Chemistry, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
Phone: 00987143311145; fax: 00987143311172; e-mail: soheilaghassamipour@miau.ac.ir
Abstract: We report a one-pot method for the synthesis of various substituted 1,3-dimethyl-
2,4,6-trioxohexahydropyrimidin-5-yl phosphonate derivatives via phosphorus-carbon bond
formation through domino Knoevenagel–phospha–Michael reaction. Multi-walled carbon
nanotube-CO-NH(CH2)2NH-SO3H was used as an acidic heterogeneous catalyst. The catalyst
could be used four times without losing its catalytic activity. The structures of the products
1
were determined by FT-IR spectra, H-, 13C- and 31P- Nuclear Magnetic Resonance and
elemental analysis. Recovery and reusability of catalyst, simplicity, applicability, good
reaction time and good yields of products are the benefits of this work.
Keywords: domino Knoevenagel–phospha–Michael reaction, organophosphonates,
triethylphosphite, 3,3-dimethyl barbituric acid, multi-walled carbon nanotube-CO-
NH(CH2)2NH-SO3H, heterogeneous catalyst
Introduction
Barbituric acid and its derivatives have a special place in medicinal chemistry. A literature
survey shows that chemical compounds containing barbituric acid ring have biological
activity such as hypnotic,1 anaesthetic,2 anticonvulsant,3 antibacterial,4 anticancer and
antitumor properties.5 In addition, this ring was used in structure of dye-sensitized solar-
cells.6 On the other hand, organophosphorus compounds are one of the most important

organic compounds that are present in human body and animals.7 In this family, phosphonic
acids and their derivatives have attracted considerable attention from organic chemists. There
8,9
are many reports in literature for biological activity
and applications of phosphonic acid
derivatives in industry, agriculture and medicinal chemistry.10-14 Nowadays, multi-component
reactions play an essential role in organic synthesis.15 Domino Knoevenagel-phospho-
Michael reaction is the most famous multi-component reactions for P-C bond formation.16
Despite the extensive range of investigations on the synthesis of various types of organic
phosphonates,17 In continued our research in preparation of new phosphonates,18 we decided
to employ the domino Knoevenagel–phospha–Michael route for the synthesis of new
organophosphonates by reaction between aromatic aldehydes, 3,3-dimethyl barbituric acid,
triethylphosphite using multi-walled carbon nanotube-CO-NH(CH2)2NH-SO3H as a catalyst.
Lately this catalyst was synthesized and identified by our research team and was used as
adsorbent for the removal of the dye from water.19 Carbon nanotubes (CNTs) have been
considered in science and technology due to simplicity and ease of synthesis. These
nanostructures have the novel properties such as high surface area, good stiffness, and
resilience.20 Carbon nanotubes have the variety of applications in the area of
microelectronics/nanoelectronics,21
spintronics,22
optics,23
biotechnology
and
biomedicine.24These compounds are also very important in chemistry, for example, CNTs are
27
one of the best materials for air filters,25 water filters,26 chemical Nanowires,
adsorbents for the removal of dyes and metal ions in waste29 and catalytic activity.30
sensors,28
Results and discussions
We studied the reaction between 4-nitrobenzaldehyde (1mmol), 3,3-dimethylbarbituric acid
(1 mmol) and triethylphosphite (1.1 mmol) in the presence of multi-walled carbon nanotube-
CO-NH(CH2)2NH-SO3H as a catalyst. The model reaction was optimized by various
experimental parameters such as solvent, temperature, reaction time and catalyst (Table 1). A
mixture of products were formed in aprotic solvents such as dichloromethane, dichloroethane
and dimethyl sulfoxide at room temperature (Table 1, Entries 3, 5, 6 and 10). The number of
products decreased with increasing the temperature. For example, Knoevenagel product (3a)
is the major product in halogenated solvents (Table 1, Entries 4 and 10) and minor product
under solvent-free conditions (Table 1, Entries 1 and 2). On the other, one product was
formed in ethanol (Table 1, Entries 7 and 8). A comparison between these results show that
the use of ethanol as solvent is more suitable than the other solvents and solvent-free
2

conditions. The change in temperature from room temperature to 78°C increased isolated
yield (from 87 to 99 %, Entries 7 and 8, Table 1) and decreased reaction time (from 1 h to 45
min., Entries 7 and 8, Table 1). Finally, decreasing the amount of catalyst decrease isolated
yield and increase reaction time (Table 1, Entries 11 and 12). So, the optimal conditions
were chpsen from entry 8 in Table 1.
With these optimized results in hand, we expanded the current method for the synthesis of
other organophosphonates. For this purpose, a range of different aromatic aldehydes were
reacted with 3,3-dimethyl barbituric acid and triethylphosphite in the presence of 0.75 mol of
nano catalyst at reflux temperature in ethanol (Scheme 1, Table 2).
According to Table 2, various substituted 1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl
phosphonate derivatives (2a-i) with electron-donating and electron-withdrawing groups were
synthesized from good to excellent yields. The highest yield was obtained with 4-nitro
benzaldehyde, 1a (Entry 1) and diethyl ((1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)
(p-tolyl)methyl)phosphonate, 2i, was detected with the lowest yield (Entry 9). Under the
reaction conditions, 5-bromo-2-hydroxybenzaldehyde, 1c, and 2-hydroxy-5-nitro
benzaldehyde, 1d, (Entries 3 and 4) converted to desired products and ring closing products
were not formed. Some of ortho-substituted aldehydes (Entries 5 and 7) was generated of
trace amount of Knoevenagel products (3e and 3g).
After the centrifution of the reaction mixture, heterogeneous nanocatalyst was precipitated.
This catalyst was dried and reused in the same reaction. Multi-walled carbon nanotube-CO-
NH(CH2)2NH-SO3H was used four times without losing catalytic activity. The results have
shown in Table S 1 (Supplemental Materials).
Briefly, a one-pot route was introduced for the synthesis of various substituted 1,3-dimethyl-
2,4,6-trioxohexahydropyrimidin-5-yl phosphonate derivatives via domino-Knoevenagel-
phospha-Michael reaction between aromatic aldehydes, 3,3-dimethyl barbituric acid and
triethyl phosphite catalyzed by multi-walled carbon nanotube-CO-NH(CH2)2NH-SO3H as
new heterogenous nanocatalyst. The benefits of this reaction include: recyclability and
reusability of catalyst, simplicity, applicability, good reaction time and good yields of
products.
3

Experimental
The chemical materials were supplied from Merck Chemical Company. Multi-walled carbon
nanotube was supplied by Industrial Research Institute of Tehran with the following
characteristics: inner diameter, 3.8 nm; outer diameter, 10-30 nm; length, 10 µm, purity 99%;
special surface, 270 m2g-1 and thermal conductivity 1500 Wm-1k-1. Nuclear Magnetic
Resonance spectra were recorded on Ultra shield Bruker 400 and Bruker Avance 250.
Melting points were determined in open capillary tubes in a Büchi-545 circulating oil melting
point. Elemental analysis were recorded on a vario EL automated analyzer, model 11086109.
1
13
31
The Supplemental Materials contains sample H, C and P NMR spectra of products 2
(Figures S 1 – S 27).
General procedure for the synthesis of 1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-
yl phosphonate derivatives (2a-i)
Nano catalyst (0.75 mol) was added to a mixture of aldehyde (1 mmol), 3,3-dimethyl
barbituric acid (1 mmol) and triethylphosphite (1.1 mmol) in 3 mL of ethanol. The reaction
mixture was stirred at 78°C for the appropriate time according to Table 2. The progress of the
reaction was monitored by TLC (eluent: n-hexane/ethyl acetate 5:1). Then, the mixture was
centrifuged and filtrated. The filtrate was purified by silica gel column chromatography with
n-hexane and ethyl acetate to give the pure product. The residual catalyst was dried under
vacuum at 80 °C for 8 h and reused without more purification.
Spectral data:
((1,3-Dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)(4-nitrophenyl)methyl)
phosphonate (2a)
FT-IR (KBr, cm-1): 1608 (C=O), 1509 (C=C), 1479 (sym. str. NO2), 1340 (C-N), 1250 (sym.
str. NO2), 1200 (P=O), 1044 (P-O). 1H-NMR (250 MHz, CDCl3, δ/ppm): 2.25-2.31 (t, J=7.4
HZ, 6H, -OCH2CH3), 3.17 (s, 6H, CH3), 3.26-3.28 (d, J=3.6 Hz, 1H, -CO-CH-CO-), 3.98-
4

4.03 (q, J=7.2 Hz, 4H, -OCH2CH3), 4.13-4.16 (dd, J1=, J2= 2.8 Hz, 1H, -CH-PO-), 7.06 (d,
13
J= 2.7 Hz, 2H, arom.), 7.19 (d, J= 2.7 Hz, 2H, arom.). C-NMR (63 MHz, CDCl3, δ/ppm):
31
16.1, 27.3, 29.6, 31.9, 55.6, 123.9, 126.1, 137.4, 143.2, 154.4, 166.6, 167.1. P-NMR (162
MHz, CDCl3, δ/ppm, 85% aqueous H3PO4 as external reference): 19.7. Anal. Calc. for
C17H22N3O8P (427.35): C, 47.78; H, 5.19; N, 9.83 %. Found: C, 47.52; H, 5.13; N, 9.85 %.
Diethyl((4-bromophenyl)(1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)methyl)
phosphonate (2b)
FT-IR (KBr, cm-1): 1691 (C=O), 1634 (C=C), 1347 (C-N), 1205 (P=O), 1079 (P-O), 577 (C-
1
Br). H-NMR (250 MHz, CDCl3, δ/ppm): 1.26-1.32 (t, J=7.02 HZ, 6H, -OCH2CH3), 3.32 (s,
3H, CH3), 3.36 (s, 3H, CH3), 3.63-3.71 (q, J=7.05 Hz, 4H, -OCH2CH3), 4.75 (s, 1H, -CO-
CH-CO-), 5.32-5.37 (d, J= 11.7 HZ, -CH-PO-), 7.53-7.57 (d, J= 8.6 HZ, 2H, arom.), 7.87-
7.91 (d, J= 8.6 HZ, 2H, arom.). 13C-NMR (63 MHz, CDCl3, δ/ppm):16.3, 29.6, 31.1, 31.3,
32.0, 55.1, 120.6, 121.7, 131.6, 133.7, 150.5, 169.3, 170.4. 31P-NMR (162 MHz, DMSO-d6,
δ/ppm, 85% aqueous H3PO4 as external reference):19.7. Anal. Calc. for C17H22BrN2O6P
(461.24): C, 44.27; H, 4.81; N, 6.07 %. Found: C, 44.01; H, 4.83; N, 6.11 %.
Diethyl((5-bromo-2-hydroxyphenyl) (1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-
yl)methyl)phosphonate (2c)
FT-IR (KBr, cm-1): 3492 (str. OH), 1591 (C=O), 1629 (C=C), 1369 (C-N), 1198 (P=O), 1011
1
(P-O), 562 (C-Br). H-NMR (400 MHz, DMSO-d6, δ/ppm): 1.02-1.06 (m, 6H, -OCH2CH3),
2.90 (s, 6H, CH3), 4.00 (m, 4H, -OCH2CH3), 4.80 (s, 1H, -CO-CH-CO-), 5.88-5.90 (d, J= 8.8
Hz, 1H, -CH-PO), 7.29-7.51 (m, 2H, arom.), 7.55-7.63 (m, 1H, arom.), 10.9 (s, 1H, OH). 13C-
NMR (100 MHz, DMSO-d6, δ/ppm): 17.1, 27.8, 28.9, 35.3, 54.3, 117.5, 118.9, 122.5, 130.6,
31
134.1, 151.1, 154.0, 166.7, 167.2. P-NMR (162 MHz, DMSO-d6, δ/ppm, 85% aqueous
H3PO4 as external reference):19.6. Anal. Calc. for C17H22BrN2O7P (477.24): C, 42.78; H,
4.65; N, 5.87 %. Found: C, 42.81; H, 4.69; N, 5.91 %.
Diethyl((1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)(2-hydroxy-5-nitrophenyl)
methyl)phosphonate (2d)
FT-IR (KBr, cm-1): 3480 (str. OH), 1667 (C=O), 1610 (C=C), 1457 (asym. str. NO2), 1348
1
(C-N), 1254 (sym. str. NO2), 1198 (P=O), 1003 (P-O), H-NMR (400 MHz, DMSO-d6,
δ/ppm): 1.09-1.13 (t, J=7.2 Hz, 6H, -OCH2CH3), 2.99 (s, 6H, CH3), 3.61-3.76 (m, 4H, -
5

OCH2CH3), 4.31 (s, 1H, -CO-CH-CO-), 5.14-5.16 (d, J=9.2 Hz, 1H, -CH-PO-), 8.08-8.09 (m,
13
2H, arom.), 8.28-8.31 (m, 1H, arom.), 9.04 (1H, OH). C-NMR (100 MHz, DMSO-d6,
δ/ppm): 18.5, 27.7, 29.0, 33.5, 54.3, 115.9, 125.0, 126.0, 128.6, 144.3, 148.2, 161.0, 166.6,
167.2. 31P-NMR (162 MHz, DMSO-d6, δ/ppm, 85% aqueous H3PO4 as external reference):
18.5. Anal. Calc. for C17H22N3O9P (443.35): C, 46.05; H, 5.00; N, 9.48 %. Found: C, 46.43;
H, 5.31; N, 9.51 %.
Diethyl((2,4-dichlorophenyl)(1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)methyl)
phosphonate (2e)
FT-IR (KBr, cm-1): 1594 (C=O), 1590 (C=C), 1373 (C-N), 1254 (P=O), 1160 (C-Cl), 1069
(P-O). 1H-NMR (400 MHz, DMSO-d6, δ/ppm): 1.02-1.06 (t, J=7.2 Hz, 6H, -OCH2CH3), 3.11
(s, 3H, CH3), 3.22 (s, 3H, CH3), 3.41 (s, 1H, -CO-CH-CO), 4.40-4.45 (q, J=6.8 Hz, 4H, -
OCH2CH3), 5.28 (s, 1H, -CH-PO), 7.46-7.49 (m, 1H, arom.), 7.67-7.74 (m, 1H, arom.), 8.28
(s, 1H, arom.). 13C-NMR (100 MHz, DMSO-d6, δ/ppm): 17.5, 27.7, 28.5, 36.6, 54.4, 122.0,
31
126.7, 128.4, 131.6, 132.8, 133.8, 135.4, 149.4, 151.0, 159.6, 161.2. P-NMR (162 MHz,
DMSO-d6, δ/ppm, 85% aqueous H3PO4 as external reference): 19.9. Anal. Calc. for
C17H21Cl2N2O6P (451.24): C, 45.25; H, 4.69; N, 6.21 %. Found: C, 44.98; H, 4.65; N, 6.24
%.
Diethyl((4-cyanophenyl)(1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)methyl)
phosphonate (2f)
FT-IR (KBr, cm-1): 2229 (CN), 1567 (C=O), 1560 (C=C), 1373 (C-N), 1215 (P=O), 1012 (P-
O). 1H-NMR (250 MHz, CDCl3, δ/ppm): 1.20-1.25 (t, J=6.9 Hz, 6H, -OCH2CH3), 3.35 (s,
3H, CH3), 3.44 (s, 3H, CH3), 4.25 (s, 1H, -CO-CH-CO-), 4.50-4.58 (q, J=6.5 Hz, 4H, -
OCH2CH3), 5.62 (s, 1H, -CH-PO-), 7.26-7.32 (m, 2H, arom.), 7.58-7.73 (m, 2H, arom.). 13C-
NMR (100 MHz, CDCl3, δ/ppm): 18.7, 27.0, 29.7, 38.0, 56.0, 115.9, 122.0, 124.5, 127.1,
128.8, 129.5, 132.4, 148.7, 150.0. 31P-NMR (162 MHz, CDCl3, δ/ppm,85% aqueous H3PO4
as external reference): 19.0. Anal. Calc. for C18H22N3O6P (407.36): C, 53.07; H, 5.44; N,
10.32 %. Found: C, 52.88; H, 5.47; N, 10.35 %.
Diethyl((1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)(2-methoxyphenyl)methyl)
phosphonate (2g)
6

FT-IR (KBr, cm-1): 1591 (C=O), 1580 (C=C), 1509 (C-O), 1373 (C-N), 1251 (P=O), 1039
(P-O). 1H-NMR (400 MHz, DMSO-d6, δ/ppm): 1.06-1.08 (t, J=6.8 Hz, 6H, -OCH2CH3), 3.14
(s, 3H, CH3), 3.21 (s, 3H, CH3), 3.86 (s, 1H, -CO-CH-CO-), 3.88 (s, 3H, -OCH3), 4.52 (m,
4H, -OCH2CH3), 5.25-5.28 (d, J=12.8 Hz 1H, -CH-PO-), 6.96-7.11 (m, 3H, arom.), 7.48-7.52
(m, 1H, arom.). 13C-NMR (100 MHz, DMSO-d6, δ/ppm): 18.4, 27.9, 28.3, 38.8, 40.1, 55.8,
110.9, 119.4, 132.1, 133.9, 150.8, 151.1, 158.8, 160.1, 162.1. 31P-NMR (162 MHz, DMSO-
d6, δ/ppm, 85% aqueous H3PO4 as external reference): 19.4. Anal. Calc. for C18H25N2O7P
(412.37): C, 52.43; H, 6.11; N, 6.79 %. Found: C, 52.40; H, 6.15; N, 6.76 %.
Diethyl((1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)(4-methoxyphenyl)methyl)
phosphonate (2h)
FT-IR (KBr, cm-1): 1590 (C=O), 1580 (C=C), 1509 (C-O), 1371 (C-N), 1250 (P=O), 1041
(P-O). 1H-NMR (400 MHz, DMSO-d6, δ/ppm): 1.04-1.09 (t, J=6.8 Hz, 6H, -OCH2CH3),
3.20 (s, 6H, CH3), 3.37(s, 1H, -CO-CH-CO-), 3.88 (s, 3H, -OCH3), 4.65-4.68 (m, 4H, -
OCH2CH3), 5.10-5.12 (d, J=8.0 Hz 1H, -CH-PO-), 7.06-7.07 (m, 2H, arom.), 8.30-8.34 (m,
2H, arom.). 13C-NMR (100 MHz, DMSO-d6, δ/ppm):17.9, 27.3, 28.0, 38.0, 52.2, 55.6, 113.8,
125.1, 137.3, 155.7, 160.7, 162.5, 163.4. 31P-NMR (162 MHz, DMSO-d6, δ/ppm, 85%
aqueous H3PO4 as external reference): 27.2. Anal. Calc. for C18H25N2O7P (412.37): C, 52.43;
H, 6.11; N, 6.79 %. Found: C, 52.39; H, 6.13; N, 6.81 %.
Diethyl((1,3-dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl)(p-tolyl)methyl)
phosphonate (2i)
FT-IR (KBr, cm-1): 1675 (C=O), 1574 (C=C), 1352 (C-N), 1267 (P=O), 1119 (P-O).1H-NMR
(400 MHz, DMSO-d6, δ/ppm):1.11-1.15 (t, J=6.8 Hz, 6H, -OCH2CH3), 2.58 (s, 3H, Ar-CH3),
3.27 (s, 6H, CH3), 3.35 (s, 1H, -CO-CH-CO-), 4.64-4.67(d, J=12.4 Hz 1H, -CH-PO-), 4.90-
13
5.03 (m, 4H, -OCH2CH3), 7.38 (m, 3H, arom.), 7.64-7.66 (m, 1H, arom.). C-NMR (100
MHz, DMSO-d6, δ/ppm):16.0, 18.5, 27.7, 27.8, 36.3, 54.3, 118.9, 130.6, 132.1, 148.6, 149.8,
154.0, 166.7, 167.0. 31P-NMR (162 MHz, DMSO-d6, δ/ppm, 85% aqueous H3PO4 as external
reference): 21.1. Anal. Calc. for C18H25N2O6P (396.37): C, 54.54; H, 6.36; N, 7.07 %. Found:
C, 54.50; H, 6.34; N, 7.16 %.
7

5-(2,4-Dichlorobenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (3e)
1H-NMR (400 MHz, DMSO-d6, δ/ppm): 3.11 (s, 3H, CH3), 3.22 (s, 3H, CH3), 7.46-7.49 (m,
13
1H, arom.), 7.67-7.74 (m, 2H, arom.), 8.28 (s, 1H, CH). C-NMR (100 MHz, DMSO-d6,
δ/ppm): 27.9, 28.5, 122.0, 126.7, 128.4, 131.6, 135.4, 149.4, 151.0, 159.6, 161.2.
5-(2-Methoxybenzylidene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (3g)
1H-NMR (400 MHz, DMSO-d6, δ/ppm):3.20 (s, 3H, CH3), 3.22 (s, 3H, CH3), 3.88 (s, 3H, -
13
OCH3), 7.05-7.07 (m, 2H, arom.), 8.30-8.34 (m, 2H, arom. and 1H, CH). C-NMR (100
MHz, DMSO, δ/ppm): 27.9, 28.4, 55.8, 110.9, 118.4, 119.4, 121.6, 132.1, 133.9, 150.8,
158.8, 160.1, 162.1.
Acknowledgments
We gratefully acknowledge the financial support of this work by Marvdasht Islamic Azad
University research council.
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11

O
N
N
O
O
O
O
O
H
catalyst (0.75 mol)
OEt
N
N
P(OEt)3
R
P
R
OEt
O
Ethanol/reflux
O
1.1 mmol
1mmol
1mmol
2 (a-i)
1 (a-i)
O
NH
SO3H
N
H
O
O
NH
NH
catalyst
=
SO3H
SO3H
N
H
N
H
MWCNTs-CONH(CH2)2NH-SO3H
Scheme 1 Domino reaction for the one-pot synthesis of new organophosphonates
12

Table 1. Optimization of model reaction
O
O
N
N
O
N
N
O
O
O
O
OEt
catalyst (0.25-1 mol)
solvent/temp.
O
H
O
P(OEt)3
N
N
P
O2N
OEt
O
O
O2N
O2N
(2a)
(3a)
Entry
Solvent
Amount of catalyst
(mol)
Temperature
(°C)
Time (h)
Isolated Yields (%)
2a
3a
35
20
1
2
Solvent-free
Solvent-free
CH2Cl2
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.5
rt
3
1
50
65
a
100
3
rt
24
1
4
CH2Cl2
reflux
rt
30
65
5
DMSO
24
24
1
a
a
6
DMSO
reflux
rt
7
Ethanol
87
-
-
8
Ethanol
reflux
rt
45 (min) 99
9
(CH2)2Cl2
(CH2)2Cl2
Ethanol
24
a
10
11
12
13
reflux
reflux
reflux
reflux
24
20
75
2
2
85
-
Ethanol
0.25
1
70
99
-
-
Ethanol
30 (min)
a Mixture of products were formed
13

Table 2. One-pot synthesis of new organophosphonates via domino Knoevenagel–phospha–Michael reaction
catalyzed by functionalized multi-walled carbon nanotube
Rf*
Entry
1
Aldehyde 1(a-i)
Product 2(a-i)
Time (min)
45
Isolated Yield (%)
99
Melting Point (°C)
186-188
O
H
O
N
N
0.37
2a
2b
O2N
O
O
OEt
1a
P
OEt
O
H
O
O
O2N
60
90
90
56
175-178
272-274
0.47
0.34
N
N
Br
1b
O
O
OEt
P
OEt
O
O
Br
Br
O
H
3
4
5
N
N
OH
1c
O
2c
2d
2e
O
OEt
Br
P
O
OEt
O
O2N
H
OH
O
60
60
73
87
240-243
184-186
0.33
0.31
OH
1d
N
N
O
O
OEt
O2N
P
OEt
O
Cl
O
OH
O
H
N
N
Cl
1e
1f
O
O
OEt
P
OEt
O
Cl
Cl
O
N
N
6
7
60
83
58
176-178
168-170
0.34
0.30
O
O
OEt
P
OEt 2f
O
NC
OMe O
O
H
N
N
1g
120
O
O
OEt
P
OEt
O
OMe
2g
O
N
N
O
O
OEt
8
9
90
70
53
141-145
260-258
0.47
0.47
1h
P
OEt
2h
O
MeO
O
N
N
O
O
OEt
120
P
2i
OEt
1i
O
Me
14

*Rf was determined in n-hexane-ethyl acetate (80%-20%) on silica gel as stationary phase
15