Ultrasound-promoted solvent-free synthesis of some new α-aminophosphonates as potential antioxidants

Article abstract of DOI:10.1515/mgmc-2020-0018

Ultrasonic irradiation has been adopted in order to achieve an efficient synthesis of some novel α-aminophosphonates by Pudovik reaction. Major benefits of this method are as follows: Eco-friendly, free of catalyst, high yielding, uncomplicated work-up pr

Full text of DOI:10.1515/mgmc-2020-0018

Main Group Met. Chem. 2020; 43: 147–153
Research Article
Open Access
Meson Haji Basha, Chennamasetty Subramanyam* and Kammela Prasada Rao*
Ultrasound-promoted solvent-free synthesis of
some new α-aminophosphonates as potential
antioxidants
https://doi.org/10.1515/mgmc-2020-0018
Received November 07, 2019; accepted July 06, 2020.
(
Subramanyam et al., 2017), antifungal (Yang et al., 2006),
antiviral (Xu et al., 2006), anti-inflammatory agents
Abstract: Ultrasonic irradiation has been adopted in (Sujatha et al., 2017), anti-HIV (Bhattacharya et al., 2012),
order to achieve an efficient synthesis of some novel anticancer (Bahrami et al., 2016), anti-proliferative and
α-aminophosphonates by Pudovik reaction. Major apoptosis inducing (Huang et al., 2016a, 2016b; Li et al.,
benefits of this method are as follows: eco-friendly, 2015), antitumor (Liu et al., 2017), herbicidal activity (Che
free of catalyst, high yielding, uncomplicated work-up et al., 2016) and insecticidal activity (Jiang et al., 2013;
procedure, short reaction time, and solvent free condition. Liu et al., 2012). Addition of trialkyl or dialkylphosphite
Spectral characterisation and elemental analysis of the to imines is a successful technique to obtain them (Azizi
synthesized samples was carried out. In vitro antioxidant et al., 2004; Heydari et al., 2009; Kassaee et al., 2009;
2-
activity of the title compounds was screened by DPPH˙, O ˙ Manjula et al., 2013; Yadav et al., 2001). Many reviews
and NO˙ scavenging methods. Good activity was shown by were published using various Bronsted acids, Lewis acids,
most of the compounds as compared with the standards.
hetero poly acids, heterogeneous and nano catalysts to
accomplish this transformation (Ambica et al., 2008;
Keywords: α-aminophosphonates; ultrasonic irradiation; Anastas and Eghbali, 2010; Bhattacharya et al., 2007,
antioxidant activity
2008; Chandrasekhar et al., 2001; Heydari et al., 2007;
Mitragotri et al., 2008; Sobhani et al., 2008; Yadav et al.,
2
003; Vahdat et al., 2008). Nevertheless, most of them are
highly-expensive, corrosive and occupy tedious separation
processes and long reaction times. So that, establishment
of an environmental friendly protocol would expand the
scope of the synthesis of AAPs. In this regard, solvent free
1
Introduction
α-Aminophosphonates (AAPs) are most important group synthesis is one of the best option especially when the
of organophosphorus compounds that are structural solvents are toxic and flammable (Hung et al., 2016a).
analogues of amino acids where a carboxylic substituent is
Alternatively, synthesis of organic compounds by
substituted by phosphonic acid or related groups (Merino means of ultrasound irradiation is a successful protocol
et al., 2008). Due to their outstanding biological and which is an alternate energy source for organic reactions
physical characteristics together with their usefulness as typically accomplished by normal heating (Juarez et al.,
intermediates in synthesis; AAPs have found a wide variety 2009,2010).Oneadvantageofusingcavitationasanenergy
of applications in industry, agriculture and medicine source to promote organic reactions includes shorter
(
Moonen et al., 2004; Palacios et al., 2004; Schug and reaction times (Srivastava et al., 2009). In the cavitation
Lindner, 2005). They are discovered to be antibacterial process, the molecules of the liquid are split, produces
bubbles which further collapse in the compression cycle
during the rarefaction cycle. These quick and aggressive
*
Corresponding authors: Chennamasetty Subramanyam
implosions produce tiny-lived regions by means of
temperatures of approximately 5000°C, pressures of
and Kammela Prasada Rao, Department of Chemistry,
Bapatla Engineering College, A.P., 522101, India;
e-mail: subbusree04@gmail.com; prasad17467@gmail.com
Meson Haji Basha, PGT Chemistry, AP Model School Jr College,
M. Timmapuram, Nandhyal-518512, India
7
about 1000 atm and heating and cooling rates above 10 °C
per second. Such localized hot spots can be considered as
micro reactors where the sound energy is distorted into
Open Access. © 2020 Basha et al., published by De Gruyter.
Attribution alone 4.0 License.
This work is licensed under the Creative Commons

ꢀ
M.H. Basha et al.: Ultrasound-promoted solvent-free synthesis
1
48ꢀ
a helpful chemical form (Duarte et al., 2010; Stefani et al., Table 1:ꢀComparison of ultrasonication effect on the synthesis of
AAPs (7a-e and 8a-e).
2
005). This method is found to be a hygienic, convenient
and helpful etiquette in organic synthesis compared with
traditional methods (Srivastava et al., 2009). In an effort
to achieve higher yields with selectivity, this method is
determined to be excellent alternative in organic synthesis
a
With ultrasonicationb
Without ultrasonication
Time (h)
Entry
c
c
Yield (%)
Time (min)
Yield (%)
90
ꢀ
ꢁ
ꢀ
ꢁ
ꢀ
ꢁc
ꢀd
ꢁ
ꢀ
ꢁ
a
a
b
b
c
3
5
68
71
73
70
78
69
71
70
76
68
10
18
32
25
21
27
40
25
34
28
89
(Gallardo and Nakayama, 2010; Heydari et al., 2007).
3
93
Currently, some researchers have reported the solvent-
free synthesis of AAPs using ultrasound from amines,
aldehydes and and diethylphosphite by diverse catalysts
4
90
4.5
5
89
(
Agawane et al., 2010; Shinde et al., 2011).
85
On the basis of previous reports and present need
of merits on the synthesis of AAPs and in extension
of our research to increase new protocols (Ravikumar
et al., 2018), we focussed at the synthesis of AAPs via
Pudovik reaction under solvent-free condition using
ultrasonication. DPPH, O2- and NO methods had been
chosen to test their antioxidant activity.
3.5
3
88
d
e
e
86
4
95
3
91
a
Reaction of various imines (ꢂa-e and 5a-e) and diethylphosphite
b
(
(
6) in ethanol using TMG at 50
°
C-60°C; Reaction of various imines
ꢂa-e and 5a-e) and diethylphosphite (6) without solvent under
c
ultrasonication at optimum temperature; Isolated yield.
2
Results and discussion
7
a-e and 8a-e. The chemical shift for P–CH carbons was
observed at δ 57.5 ppm respectively for the title compounds.
31
2.1 Chemistry
P NMR signals were observed in the region 20.3-15.2 ppm
for 5a-j (Subramanyam et al., 2017). In their mass spectra,
+.
A series of AAPs, 7a-e and 8a-e were synthesized in two M ions were observed in the expected m/z values. The
steps by Pudovik reaction. At first, a series of imines (4a-e representative spectra of compound 7a were provided in
and 5a-e) were prepared by reacting equimolar quantities Supplementary material as Figures S1-S6.
of amines (1a-e) and aldehydes (2 and 3) in ethanol at
4
0°C for approximately 1h. Then, the corresponding imine
was treated with diethylphosphite (6) to give AAPs, 7a-e 2.2 Antioxidant activity
and 8a-e using both conventional approach as well as
ultrasonication methods. Table 1 and Scheme 1 represent Antioxidant activity of newly prepared compounds become
the results and the synthetic protocol of this process.
screened at concentrations 50 μg/mL and 100 μg/mL by
The chemical structures of all the title compounds 7a-e DPPH, Superoxide and Nitric oxide (NO) radical scavenging
1
13
31
and 8a-e were characterized by IR, H, C, P NMR, mass activities. The investigational results be obtainable in
spectral data and elemental analyses and their data were Table 2.
presented in the experimental section. IR absorptions in
the regions 3345-3308, 1236-1210 and 1018-1012 cm were highestDPPHradicalscavengingactivitywith%inhibition
assigned to NH, P=O and P–O–C stretching vibrations 64.2, 81.5 μg/mL, and 63.6, 80.3 μg/mL, respectively at
respectively for the title compounds (Subramanyam et al., 50 and 100 μg/mL. The remaining compounds showed
Out of all, the compounds; 7b and 7c showed the
-1
1
2
013). The H NMR spectra gave signals due to Ar-H in moderate activity while compared with the antioxidant,
the range of δ 8.13-6.82 ppm. The proton signal at δ 4.55 Ascorbic acid.
was assigned to -NH stretching vibrations of all the title
In superoxide radical scavenging activity assay,
compounds. The proton signal in the range δ 3.90-3.84 the compounds 8a, 7c, and 8c showed the highest %
as doublet was assigned to P–CH stretching vibrations inhibition 58.5, 79.5 μg/mL, 57.6, 78.4 μg/mL, and 56.3,
of all the title compounds. The methylene and methyl 77.1 μg/mL, respectively at 50 and 100 μg/mL. The
protons of P–O–CH CH resonated as multiplet and triplet remaining exhibited considerable activity with reference
2
3
-1
13
respectively at δ 4.05 and 1.18 cm . C NMR chemical to standard antioxidant, BHT.
shift for methylene and methyl carbons were observed at In NO radical scavenging activity assay, the
1.9 ppm and 16.2 ppm respectively for the title compounds compounds 7c and 7b showed the highest % inhibition
6

ꢀ
M.H. Basha et al.: Ultrasound-promoted solvent-free synthesis
ꢀ149
Conventional method
X
X
X
EtOH
r.t.
R
O
R
NH2
HP(O)(OC H )
2 5 2
N
O
R
P
O
H
(
(
4a-e)
5a-e)
O
2
; X=F
1a-e
3
; X=Cl
(7a-e)
(
8a-e)
Ultrasonication
Compd
R
X
X
Yield (%) Compd
R
Yield (%)
HN
HN
9
0
3
F
F
89
Cl
7a
8
a
N
N
S
S
9
0
5
9
N
Cl
Cl
7b
N
H
N
O
8b
8c
H
N
O
8
N
N
89
F
7c
O
N
H
N
O
N
N
H
H
H
8
6
Cl
Cl
F
F
88
95
8
d
S
N
S
N
7
d
e
91
N
N
H3C
N
N
8e
H3C
7
Scheme 1: Synthesis of AAPs (7a-e and 8a-e).
Table 2:ꢀDPPH, superoxide and NO radical scavenging activities of compounds 7a-e and 8a-e.
Compound
DPPH radical scavenging activity
inhibition
Superoxide radical scavenging activity
% inhibition
NO radical scavenging activity
% inhibition
%
50 μg/mL
ꢃ00
μg/mL
50 μg/mL
ꢃ00
μg/mL
50 μg/mL
ꢃ00
μg/mL
7
8
7
8
7
8
7
8
7
8
a
a
b
b
c
56.4
55.6
63.6
52.1
64.2
60.7
40.4
54.2
34.5
58.6
68.4
-
75.5
67.6
80.3
74.2
81.5
77.2
63.6
71.5
50.8
77.3
84.2
-
62.2
58.5
54.3
42.4
57.6
56.3
40.9
51.2
26.2
31.4
64.6
-
72.1
79.5
73.1
62.6
78.4
77.1
60.7
72.1
43.2
51.6
78.4
-
43.2
50.3
64.2
31.3
67.3
55.5
56.3
52.2
39.8
58.5
68.56
-
63.8
78.6
90.2
62.5
93.9
83.4
85.5
79.9
65.7
87.7
96.07
-
c
d
d
e
e
*
Standard
Blank

ꢀ
M.H. Basha et al.: Ultrasound-promoted solvent-free synthesis
1ꢄꢅꢀ
6
7.3, 93.9 μg/mL and 64.2, 90.2 μg/mL, respectively at 50 in ethanol at 40°C for about 1 h produced the respective
and 100 μg/mL. The remaining exhibited considerable imines (4a-e and 5a-e).
activity with reference to the usual antioxidant, BHT.
Synthesis of AAPs, 7a-e and 8a-e by conventional
heating method
3
Conclusion
In conclusion, we demonstrated right here an efficient, The imine (0.01 mole) become reacted with
cheaper, environmentally benign protocol for the diethylphosphite (6) (0.015 mole) in EtOH using
formation of AAPs by Pudovik reaction through an tetramethylguanidine (TMG) at 50°C-60°C for 3-5 h
intermediate imine using solvent and catalyst free to yield the corresponding AAPs (7a-e and 8a-e). TLC
condition. The antioxidant activity of the synthesized (ethylacetate: n-hexane, 6:4) was used for verifying the
2−
compounds was evaluated by DPPH, O and NO methods. development of the process. As soon as the reaction was
Compound 7b, bearing with 4-fluorophenyl)(thiazol-2- finished, as confirmed via TLC, the aggregate became
ylamino moiety; 7c incorporated with 4-fluorophenyl) chilled to room temperature. The pure compounds (7a-e
(
1-methyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-ylamino and 8a-e) were obtained by column chromatography
moiety and 8c bearing 4-chlorophenyl)(1-methyl-2,6- by means of n-hexane:ethyl acetate (2:3) as eluent. The
dioxo-1,2,3,6-tetrahydropyrimidin-4-ylvamino motif yield become located in the range of 68-78%.
exhibited potent antioxidant activity when in comparison
with the standard antioxidants.
Ultrasonication procedure for the synthesis of AAPs,
a-e and 8a-e
7
Experimental
The imines (4a-e and 5a-e) (0.01 mole) which received
formerly and diethylphosphite (6) (0.015 mole) were
positioned in a RB Flask and the reactants become
irradiated in ultrasonicator at room temperature for about
Materials and methods
The chemicals were purchased from Sd. Fine Chem. Ltd., 15-40 min to obtain respective AAPs (7a-e and 8a-e). TLC
India and some of them were purified using standard (ethyl acetate: n-hexane, 6:4) was used for verifying the
procedures. The purity of the compounds was checked progress of the reaction. Once the reaction was completed,
by TLC on silica gel coated Al sheet. In conventional as tested by TLC, the combination turned into chilled to
technique, the reaction was carried out on magnetic stirrer room temperature. The pure compounds (7a-e and 8a-e)
cum hot plate. Ultrasonicator, BANDELIN SONOREXR were acquired through column chromatography using
(Germany) (35 kHz, 200 W) with inbuilt heating 30°C-80°C ethyl acetate: n-hexane (3:2) as eluent. The yield of the
was used for ultrasonic irradiation technique. J (coupling synthesized compounds was observed within the range
constants) and δ (chemical shift) values were reported of 85-95%.
in Hz and ppm, respectively. Bruker AMX spectrometer
3
1
1
13
was used to record P (161.9 MHz), H (400 MHz) and C
Characterization of title compounds (7a-e and 8a-e)
(
100 MHz) NMR spectra. The symbols ‘s’ for singlet, ‘d’ for
doublet, ‘t’ for triplet and ‘m’ for multiplet were used to
represent peaks in NMR spectra. L.C. MS were recorded on
SHIMADZU 2010A. Thermo Finnigan Flash 1112 apparatus
was used for CHN analysis. Bruker IFS 55 (Equinox) FTIR
spectrometer in KBr was used to record IR spectra.
Diethyl (4-fluorophenyl)(pyridin-3-ylamino)methylphos-
phonate (7a). Yield: 90%; semi solid. δH (DMSO-d ):
6
8
.13-7.28 (m, 7H, Ar-H), 4.55 (s, 1H, -NH), 4.05 (p, 4H,
O-CH CH ), 3.86 (d, 1H, P-CH), 1.18 (t, J = 7.6 Hz, 6H,
2
3
O-CH CH ); δ (DMSO-d ): 162.3 (C-13), 147.8 (C-16), 139.5
2
3
C
6
(
C-19), 136.4 (C-21), 132.9 (C-10), 127.3 (C-11, C-15), 125.9
Procedure
(C-18), 119.1 (C-17), 116.6 (C-12, C-14), 61.9 (C-5, C-8), 57.5
(
C-1), 16.2 (C-6, C-9); δ (DMSO-d ): 16.7 ppm; IR (KBr)
P 6
-1
Synthesis of imines (4a-e and ꢄa-e)
(νmax cm ): 3326 (NH), 1233 (P=O), 1017 (P-O-Calip);
+
LCMS (m/z, %): 339 (M+H , 100); For C H FN O P;
1
6
20
2
3
The reaction of equimolar amounts of numerous amines calcd: C, 56.80; H, 5.96; N, 8.28%; found: C, 56.86;
(1a-e) (0.02 mole) with aldehydes (2 and 3) (0.02 mole) H, 5.91; N, 8.32%.

ꢀ
M.H. Basha et al.: Ultrasound-promoted solvent-free synthesis
ꢀ1ꢄ1
(
C-13), 161.4 (C-18), 132.9 (C-10), 127.3 (C-11, C-15), 116.6 (C-12,
C-14), 76.8 (C-17), 61.9 (C-5, C-8), 57.5 (C-1), 29.2 (C-22), 16.2
-1
(
C-6, C-9); δ (DMSO-d ): 20.3 ppm; IR (KBr) (ν cm ):
2
P
6
max
6
3
345 (NH), 1235 (P=O), 1018 (P-O-Calip); LCMS (m/z, %): 386
4
HN 1
(M+H , 100); For C H FN O P; calcd: C, 49.87; H, 5.49; N,
5
+
1
5
1
6
21
3
5
O 3
P
9
14
10.91%; found: C, 49.93; H, 5.42; N, 10.98%.
1
0
Diethyl (4-chlorophenyl)(1-methyl-2,6-dioxo-1,2,3,6-
tetrahydropyrimidin-4-ylamino)methylphosphonate
(8c). Yield: 85%; semi solid. δ (DMSO-d ): 10.89 (s, 1H,
8
O
7
O
13
X
1
1
1
2
H
6
CO-NH), 7.45 (d, 2H, Ar-H), 7.25 (d, 2H, Ar-H), 4.42 (s, 1H,
ethylene-H), 4.05 (p, 4H, O-CH CH ), 3.84 (d, 1H, P-CH),
Figure 1: General structure of title compounds (7a-e and 8a-e).
2
3
3
.32 (s, 3H, N-CH ), 2.17 (s, 1H, -NH), 1.18 (t, J = 7.6 Hz,
3
Diethyl
(4-chlorophenyl)(pyridin-3-ylamino)methyl- 6H, O-CH CH ); δ (DMSO-d ): 165.4 (C-16), 163.4 (C-20),
2 3 C 6
phosphonate (8a). Yield: 89%; semi solid. δ (DMSO-d ): 161.4 (C-18), 132.8 (C-10), 132.3 (C-13), 128.9 (C-12, C-14),
H
6
8
.13-7.24 (m, 7H, Ar-H), 5.20 (s, 1H, -NH), 4.05 (p, 4H, 128.3 (C-11, C-15), 76.8 (C-17), 61.9 (C-5, C-8), 57.5 (C-1),
O-CH CH ), 3.86 (d, 1H, P-CH), 1.18 (t, J = 7.6 Hz, 6H, 29.2 (C-22), 16.2 (C-6, C-9); δ (DMSO-d ): 18.6 ppm; IR
2
3
P
6
-
1
O-CH CH ); δ (DMSO-d ): 147.8 (C-16), 139.5 (C-19), 136.4 (KBr) (νmax cm ): 3334 (NH), 1234 (P=O), 1015 (P-O-Calip);
2
3
C
6
+
+
(
(
C-21), 132.8 (C-10), 132.3 (C-13), 128.9 (C-12, C-14), 128.3 LCMS (m/z, %): 402 (M+H , 100) 404 (M+2 , 33.2); For
C-11, C-15), 125.9 (C-18), 119.1 (C-17), 61.9 (C-5, C-8), 57.5 (C-1), C H ClN O P; calcd: C, 47.83; H, 5.27; N, 10.46%; found:
1
6
21
3
5
-1
1
6.2 (C-6, C-9); δ (DMSO-d ): 15.2 ppm; IR (KBr) (ν cm ): C, 47.89; H, 5.22; N, 10.52%.
P
6
max
3
321 (NH), 1227 (P=O), 1013 (P-O-Calip); LCMS (m/z, %): 355
Diethyl (4-fluorophenyl)(thiomorpholinoamino)methyl-
+
+
(
M+H , 100), 357 (M+2 , 32.7); For C H ClN O P; calcd: phosphonate (7d). Yield: 88%; semi solid. δ (DMSO-d ):
1
6
2
0
2
3
H
6
C, 54.17; H, 5.68; N, 7.90%; found: C, 54.23; H, 5.62; N, 7.96%. 7.29 (d, 2H, Ar-H), 7.15 (d, 2H, Ar-H), 4.05 (p, 4H, O-CH CH ),
2
3
Diethyl
(4-fluorophenyl)(thiazol-2-ylamino)methyl- 3.90 (d, 1H, P-CH), 2.76 (t, 4H, -CH ), 2.45 (t, 4H, -CH ), 2.12
2 2
phosphonate (7b). Yield: 93%; semi solid. δ (DMSO-d ): (s, 1H, -NH), 1.18 (t, J = 7.6 Hz, 6H, O-CH CH ); δ (DMSO-
H
6
2
3
C
7
-
.35-6.82 (m, 6H, Ar-H), 4.05 (p, 4H, O-CH CH ), 5.20 (s, 1H, d6): 162.3 (C-13), 132.9 (C-10), 127.3 (C-11, C-15), 116.6 (C-12,
2 3
NH), 3.90 (d, 1H, P-CH), 1.18 (t, J = 7.6 Hz, 6H, O-CH CH ); C-14), 61.9 (C-5, C-8), 58.9 (C-17, C-21), 57.5 (C-1), 24.8 (C-18,
2 3
δ (DMSO-d ): 164.8 (C-16), 162.3 (C-13), 138.3 (C-18), 132.9 C-20), 16.2 (C-6, C-9); δ (DMSO-d ): 18.7 ppm; IR (KBr) (ν
C
6
P
6
max
-1
(
C-10), 127.3 (C-11, C-15), 116.6 (C-12, C-14), 114.2 (C-19), 61.9 cm ): 3320 (NH), 1219 (P=O), 1014 (P-O-Calip); LCMS (m/z,
+
(
C-5, C-8), 57.5 (C-1), 16.2 (C-6, C-9); δ (DMSO-d ): 18.8 ppm; %): 363 (M+H , 100); For C H FN O PS; calcd: C, 49.71; H,
P 6 15 24 2 3
-1
IR (KBr) (νmax cm ): 3336 (NH), 1230 (P=O), 1014 (P-O-Calip); 6.68; N, 7.73%; found: C, 49.77; H, 6.62; N, 7.78%.
+
LCMS (m/z, %): 345 (M+H , 100); For C H FN O PS; calcd:
Diethyl
(4-chlorophenyl)(thiomorpholinoamino)
14
18
2
3
C, 48.83; H, 5.27; N, 8.14%; found: C, 48.89; H, 5.22; N, 8.19%. methylphosphonate (8d). Yield: 86%; semi solid. δH
Diethyl (4-chlorophenyl)(thiazol-2-ylamino)methyl- (DMSO-d ): 7.54 (d, 2H, Ar-H), 7.23 (d, 2H, Ar-H), 4.05
phosphonate (8b). Yield: 90%; semi solid. δ (DMSO-d ): (p, 4H, O-CH CH ), 3.90 (d, 1H, P-CH), 2.76 (t, 4H, -CH ),
6
H
6
2
3
2
7
.47-6.82 (m, 6H, Ar-H), 4.05 (p, 4H, O-CH CH ), 5.20 (s, 1H, 2.45 (t, 4H, -CH ), 2.12 (s, 1H, -NH), 1.18 (t, J = 7.6 Hz, 6H,
2 3 2
NH), 3.90 (d, 1H, P-CH), 1.18 (t, J = 7.6 Hz, 6H, O-CH CH ); O-CH CH ); δ (DMSO-d ): 132.3 (C-13), 132.8 (C-10), 128.9
-
2 3 2 3 C 6
δ (DMSO-d ): 164.8 (C-16), 132.3 (C-13), 132.8 (C-10), 138.3 (C-12, C-14), 128.3 (C-11, C-15), 61.9 (C-5, C-8), 58.9 (C-17,
C
6
(
C-18), 128.9 (C-12, C-14), 128.3 (C-11, C-15), 114.2 (C-19), 61.9 C-21), 57.5 (C-1), 24.8 (C-18, C-20), 16.2 (C-6, C-9); δ (DMSO-
P
-1
(
C-5, C-8), 57.5 (C-1), 16.2 (C-6, C-9); δ (DMSO-d ): 16.9 ppm; d6): 18.3 ppm; IR (KBr) (νmax cm ): 3315 (NH), 1212 (P=O),
P 6
-1
+
+
IR (KBr) (νmax cm ): 3328 (NH), 1222 (P=O), 1012 (P-O-Calip); 1012 (P-O-Calip); LCMS (m/z, %): 379 (M+H ,100) 381 (M+2 ,
+
+
LCMS (m/z, %): 360 (M+H , 100), 362 (M+2 , 32.7); For 36.6); For C H ClN O PS; calcd: C, 47.55; H, 6.39; N, 7.39%;
1
5
24
2
3
C H ClN O PS; calcd: C, 46.61; H, 5.03; N, 7.76%; found: found: C, 47.61; H, 6.32; N, 7.45%.
14
18
2
3
C, 46.67; H, 5.09; N, 7.70%.
Diethyl (4-fluorophenyl)(1-methyl-2,6-dioxo-1,2,3,6- methylphosphonate (7e). Yield: 95%; semi solid. δH
tetrahydropyrimidin-4-ylamino)methylphosphonate (DMSO-d ): 7.29 (d, 2H, Ar-H), 7.15 (d, 2H, Ar-H), 4.05 (p,
Diethyl (4-fluorophenyl)(4-methylpiperazin-1-ylamino)
6
(
7c). Yield: 89%; semi solid. δ (DMSO-d ): 10.89 (s, 1H, 4H, O-CH CH ), 3.90 (d, 1H, P-CH), 2.72 (m, 4H, -CH ), 2.32
H
6
2
3
2
CO-NH), 7.28 (d, 2H, Ar-H), 7.19 (d, 2H, Ar-H), 4.42 (s, 1H, (s, 3H, -CH ), 2.28 (m, 4H, -CH ), 2.12 (s, 1H, -NH), 1.18
3
2
ethylene-H), 4.05 (p, 4H, O-CH CH ), 3.84 (d, 1H, P-CH), (t, J = 7.6 Hz, 6H, O-CH CH ); δ (DMSO-d ): 162.3 (C-13),
2
3
2
3
C
6
3
.32 (s, 3H, N-CH ), 2.17 (s, 1H, -NH), 1.18 (t, J = 7.6 Hz, 6H, 132.9 (C-10), 127.3 (C-11, C-15), 116.6 (C-12, C-14), 61.9 (C-5,
3
O-CH CH ); δ (DMSO-d ): 165.4 (C-16), 163.4 (C-20), 162.3 C-8), 57.5 (C-1), 56.1 (C-17, C-21), 51.2 (C-18, C-20), 46.6 (C-22),
2
3
C
6

ꢀ
M.H. Basha et al.: Ultrasound-promoted solvent-free synthesis
1ꢄ2ꢀ
-
1
1
6.2 (C-6, C-9); δ (DMSO-d ): 17.7 ppm; IR (KBr) (ν cm ): Acknowledgements: Authors thanks to Dr. C. Naga
P
6
max
3
313 (NH), 1212 (P=O), 1015 (P-O-Calip); LCMS (m/z, %): Raju, Department of Chemistry, S. V. University, Tirupati
60 (M+H , 100); For C H FN O P; calcd: C, 53.47; H, 7.57; for his constant support; Lila Impex pharmaceuticals,
+
3
16
27
3
3
N, 11.69%; found: C, 53.53; H, 7.52; N, 11.75%.
Vijayawada and HCU, Hyderabad for providing spectral
Diethyl
(4-chlorophenyl)(4-methylpiperazin-1- data.
ylamino)methylphosphonate (8e). Yield: 91%; semi solid.
δ (DMSO-d ): 7.37 (d, 2H, Ar-H), 7.17 (d, 2H, Ar-H), 4.05 Conflict of interest: The authors declare that there is no
H
6
(
p, 4H, O-CH CH ), 3.90 (d, 1H, P-CH), 2.72 (m, 4H, -CH ), conflict of interest about the eBook of this newsletter.
2
3
2
2
.32 (s, 3H, -CH ), 2.28 (m, 4H, -CH ), 2.12 (s, 1H, -NH), 1.18
3 2
(
t, J = 7.6 Hz, 6H, O-CH CH ); δ (DMSO-d ): 132.8 (C-10),
2 3 C 6
1
32.3 (C-13), 128.9 (C-12, C-14), 128.3 (C-11, C-15), 61.9 (C-5,
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