Ultrasound-promoted, rapid and green synthesis of phosphonamide derivatives under catalyst and solvent-free conditions

Article abstract of DOI:10.1080/10426507.2020.1854254

We report a rapid, efficient, economic, environmentally benign, and easy to scale-up method for the synthesis of phosphonamide derivatives using ultrasound irradiation, under catalyst and solvent-free conditions starting from the corresponding amine and phenyl phosphonic dichloride. The reaction was achieved in excellent isolated yield in a short reaction time at room temperature. The structures of the synthesized compounds are confirmed by elemental analysis as well as by IR and ¹H, ¹³C, ³¹P NMR spectroscopic data and mass spectrometry.

Full text of DOI:10.1080/10426507.2020.1854254

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Ultrasound-promoted, rapid and green synthesis
of phosphonamide derivatives under catalyst and
solvent-free conditions
Fouzia Bouchareb , Malika Berredjem , Abdeslem Bouzina & Meriem Guerfi
To cite this article: Fouzia Bouchareb , Malika Berredjem , Abdeslem Bouzina & Meriem Guerfi
(2020): Ultrasound-promoted, rapid and green synthesis of phosphonamide derivatives under
catalyst and solvent-free conditions, Phosphorus, Sulfur, and Silicon and the Related Elements,
DOI: 10.1080/10426507.2020.1854254
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2020.1854254
Ultrasound-promoted, rapid and green synthesis of phosphonamide derivatives
under catalyst and solvent-free conditions
Fouzia Bouchareba,b, Malika Berredjema, Abdeslem Bouzinaa, and Meriem Guerfia
aLaboratory of Applied Organic Chemistry, Synthesis of Biomolecules and Molecular Modelling Group, Faculty of Sciences, Department of
b
Chemistry, Badji-Mokhtar – Annaba University, Annaba, Algeria; Department of Chemistry, Faculty of Sciences and Technology, Chadli
Bendjedid – EL Tarf University, El Tarf, Algeria
ABSTRACT
ARTICLE HISTORY
Received 4 August 2020
Accepted 18 November 2020
We report a rapid, efficient, economic, environmentally benign, and easy to scale-up method for
the synthesis of phosphonamide derivatives using ultrasound irradiation, under catalyst and solv-
ent-free conditions starting from the corresponding amine and phenyl phosphonic dichloride. The
reaction was achieved in excellent isolated yield in a short reaction time at room temperature.
The structures of the synthesized compounds are confirmed by elemental analysis as well as by IR
KEYWORDS
Green chemistry;
phenylphosphonic dichlo-
ride; phosphonamide;
ultrasound irradiation
1
and H, 13C, 31P NMR spectroscopic data and mass spectrometry.
GRAPHICAL ABSTRACT
Introduction
been described and some clinical trials are under develop-
ment from a chemotherapy perspective as inhibitors of
matrix metalloproteinases MMP-1, MMP-3, and MMP-9 1,
2,[5–8] inhibitors of tumor necrosis factor-a converting
enzyme (TACE) 3[9] (Figure 1).
The phosphonamide functional group is a key structural fea-
ture present in a number of biologically active natural prod-
ucts such as phosmidosine,[1] agrocin 84,[2] and microcin.[3]
Compounds containing the phosphonamide moiety are
important in biochemistry because a very large number of
the compounds of biological interest belong to this family:
Phosphonamides are important for the synthesis of vari-
ous bioactive compounds serving as natural products, phos-
DNA, RNA, and nucleotides.[4] Many applications have phates, phosphonopeptides, amino acids analogues,
CONTACT Malika Berredjem
mberredjem@yahoo.fr
malika.berredjem@univ-annaba.org
Laboratory of Applied Organic Chemistry, Synthesis of
Biomolecules and Molecular Modelling Group, Faculty of Sciences, Department of Chemistry, Badji-Mokhtar – Annaba University, Annaba 23000, Algeria.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2020.1854254.
ß 2020 Taylor & Francis Group, LLC

2
F. BOUCHAREB ET AL.
Figure 1. Examples of bioactive molecules containing phosphonamide moiety.
Figure 2. Structures of phosphonamides prepared by the conventional method.
Scheme 1. Synthesis of phosphonamides under ultrasound irradiation.
prodrugs, pharmacological agents, and as important syn- substances, the use of renewable raw materials, and greater
thetic precursors.[10–13] Despite the importance of phospho- energy efficiency of products. With the awareness of the
namides, their synthesis requires harsh conditions and/or environmental impact of human activities and the emer-
the use of halides or precious transition metals.[14] The quest gence of the concept of sustainable development, chemists
for green procedures has become of paramount importance strive to put principles into practice by developing methods
for organic chemists in the last decade.[15] Discovery of aimed at minimizing chance during synthesis, and have con-
benign, green and atom economic processes is one of the trol over reactivity in order to avoid the production of
current corner stones for chemists.[16] One of the most undesirable compounds and thus limit the quantities of
promising ecofriendly processes is the use ultrasound irradi- waste the concepts of “Green Chemistry”.[36]
The objective of this work is to carry out the reactions
One of the main objectives of our research group is the under ultrasonic irradiation, without solvent. This powerful
ation to catalyze organic reactions.
technique became extremely efficient and attractive in syn-
thetic organic chemistry, and is able to activate many reac-
tions due to cavitational collapse. it greatly contributes to
the development of sustainable green chemistry, by respond-
ing to scientific challenges and current economic and envir-
onmental problems. Indeed, it is capable of inducing a
myriad of chemical transformations.[37]
In continuation with our research on the synthesis of
organophosphorus compounds, we report herein a simple,
green, and efficient method for the preparation of these
compounds under ultrasound irradiation techniques, solvent
and catalyst-free conditions. This technique provides higher
yields, shorter reaction times, and milder reaction condi-
tions, nontoxic, environmentally friendly solvent, in a one-
step reaction, without isolation of any intermediate thus
synthesis
a
new series of organophosphorus com-
pound,[17–25] including phosphonamides.
In previous work, we have prepared a series of bisphos-
phonamides (8) (Figure 2) in good isolated yield by conven-
tional method via a one-pot synthetic route, starting from
corresponding primary amines with phenyl phosphonic
dichloride in dry acetonitrile at ꢀ5 ꢁC.[26] We also have syn-
thesized another derivative (6, 7) (Figure 2) from amines
and aminoester or chloroacetamide with phenyl phosphonic
dichloride in dry THF at 0 ꢁC in tow steps.[27] Different pro-
cess parameters such as temperature, solvent, catalyst type,
and other factors are utilized by other researchers to prepare
these compounds in excellent isolated yield.[28–35] But the
traditional notion of yield is no longer sufficient to assess
the efficiency of chemical processes.
Sustainable chemistry requires introducing new concepts reducing time, saving money, energy, and raw
that aim to reduce or eliminate the source of hazardous materials.[38–47]

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Table 1. Synthesis of phosphonamides under ultrasound irradiation.
Entry
Substrate
Product
Time (min)
5
Yield (%)
95
a
ꢂ
b
5
5
98
97
98
91
c
d
e
10
10
f
5
90
ꢂ
g
5
5
5
5
97
94
90
92
h
i
j
(continued)

4
F. BOUCHAREB ET AL.
Table 1. Continued.
Entry
Substrate
Product
Time (min)
5
Yield (%)
90
k
l
5
95
92
m
10
n
5
5
93
95
ꢂ
o
ꢂ
p
10
15
94
97
q
r
10
89
ꢂ
[26].
irradiation. The phosphonamides 8(a–r), were prepared in a
one-pot synthetic route, starting from corresponding amine
with phenyl phosphonic dichloride in the absence of any
Results and discussion
Herein we studied the synthesis of organophosphorus com-
pounds under green chemical conditions using ultrasound

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
solvent and any catalyst after 5–15 min (Table 1), the reac- Typical experimental procedure for the synthesis of
phosphoramidates
tion was completed with an excellent yield.
Notably, no product was observed when the reaction was
realized in the absence of ultrasound irradiation even after
48 h in the same conditions this shows the essential role of
ultrasound irradiation. This excellent result encourages us to
extend this study to various structurally primary and sec-
ondary amines (Scheme 1).
In a 10 mL round bottom flask taken a mixture of phenyl-
phosphonic dichloride (1 mmol) with amine (2 mmol) was
added. Then reaction mixture was subjected to the ultra-
sonication for an appropriate time. After completion of the
reaction, as indicated by TLC, silica gel; dichloromethane:
methanol (9:1). Recrystallization of the crude product in
ether afforded pure expected bisphosphonamides 8(a–r) as
white solids.
Spectrometric methods confirmed the structures of all
1
synthesized phosphonamides; in the H NMR, the formation
of phosphonamide 8 g is confirmed by the appearance of a
singlet at 2.40 ppm of the NH group, the phenyl bound to
phosphorus atom appears between 7.90 and 7.50 ppm as
multiplet. In infrared, we observed an absorption band
toward 3155 cmꢀ1 which corresponds to NH group. The
bands of C ¼ C and P ¼ O groups appear, respectively,
Bis (ethylamino) phenylphosphine oxide (8a)
Yield: 95%. Rf¼0.65 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3435,
1512, 1200. 1H NMR (DMSO, 300 MHz): 7.60 (m, 2H,
H–Ar); 7.30 (m, 3H, H–Ar); 3.60 (s, 2H, NH); 2.75 (q,
J ¼ 7.16 Hz, 4H, CH2); 1.15 (t, J ¼ 7.30 Hz, 6H, CH3). 31P
NMR (DMSO, 100 MHz) d ¼ 16.3 ppm. 13C NMR (DMSO,
100 MHz): 131.0; 130.9; 129.9; 128.2; 127.9; 127.8; 34.4; 12.9.
MS ESIþ 30 eV m/z: 213.1 [M þ H]þ 100% calcd for
[C10H17N2OP] 212. Anal. Calcd for C10H17N2OP: C 56.59,
H 8.07, N 13.20. Found: C 56.50, H 8.00, N 13.25%.
around 1461 and 1250 cmꢀ1
observed at 16 ppm.
.
31P NMR signals of 8 g were
Experimental
Materials
Bis (propylamino) phenylphosphine oxide (8b)
The chemicals used in this work were obtained from Fluka
and Merck Chemical Company and were used without
purification.
Yield: 98%. Rf¼0.61 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3193,
1465, 1200. 1H NMR (CDCl3, 250 MHz): 7.90 (m, 2H,
H–Ar); 7.50 (m, 3H, H–Ar); 2.90 (m, 4H, CH2–NH); 2.50
(m, 2H, NH); 1.50 (m, 4H, CH2–CH3); 0.90 (t, J1¼7.31 Hz,
J2 ¼7.46 Hz, 6H, CH3). 31P NMR (CDCl3, 100 MHz)
d ¼ 16.3 ppm. 13C NMR (CDCl3, 100 MHz): 135.2; 131.5;
128.3; 128.3; 42.5; 25.3; 11.3. MS ESIþ 30 eV m/z: 241.1
[M þ H]þ 100% calcd for [C12H21N2OP] 240. Anal. Calcd
for C12H21N2OP: C 59.98, H 8.81, N 11.66. Found: C 59.90,
H 8.75, N 11.70%.
Apparatus
Infrared (IR) spectra were recorded as KBr pellets on a
Perkin-Elmer FT-600 spectrometer. Proton nuclear magnetic
resonance (1H NMR) spectra were recorded in DMSO-d6 or
CDCl3 solvents on a 250 or 300 MHz Bruker spectrometer
with tetramethylsilane (TMS) as internal reference. Chemical
shifts are reported in d units (ppm). All coupling constants
(J) are reported in Hertz. Multiplicity is indicated as s (sing-
let), d (doublet), t (triplet), m (multiplet), and combination
of these signals. Carbon nuclear magnetic resonance (13C
NMR) spectra were recorded in DMSO-d6 or CDCl3 sol-
vents at 60 or 100 MHz on a Bruker spectrometer with tetra-
methylsilane (TMS) as internal reference. Phosphorus
nuclear magnetic resonance (31P NMR) spectra were
recorded on a Brucker instrument at 100 or 121.5 MHz.
Chemical Shift (ppm) Relative to 85% H3PO4. Mass spectra
were recorded on a Shimadzu QP 1100 Ex mass spectrom-
eter operating at an ionization potential of 70 eV. All reac-
tions were monitored by thin-layer chromatography TLC on
silica Merck h60 F254 (Art. 5554) percolated aluminum
plates and were developed by Spraying with ninhydrin solu-
tion. Ultrasound assisted reactions were carried out using a
FUNGILAB ultrasonic bath with a frequency of 40 kHz and
a nominal power of 250 W. The supplemental materials con-
Bis (butylamino) phenylphosphine oxide (8c)
Yield: 97%. Rf¼0.60 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3428,
1
1506, 1467, 1269. H NMR (CDCl3, 250 MHz): 7.60 (m, 2H,
H–Ar); 7.45 (m, 3H, H-Ar); 4.75 (m, 2H, NH); 3.20 (m, 4H,
CH2–NH); 1.55 (m, 4H, CH2) ; 1.33 (m, 4H, CH2–CH3);
0.90 (t, J ¼ 8.0 Hz, 6H, CH3). 31P NMR (CDCl3, 100 MHz)
d ¼ 16.3 ppm. 13C NMR (CDCl3, 100 MHz): 135.0; 131.5;
129.6; 128.6; 47.4; 32.1; 20.0; 13.9. MS ESIþ 30 eV m/z:
269.2 [M þ H]þ 100% calcd for [C14H25N2OP] 268. Anal.
Calcd for C14H25N2OP: C 62.66, H 9.39, N 10.44. Found: C
62.62, H 9.30, N 10.50%.
Bis (tert-butylamino) phenylphosphine oxide (8d)
Yield: 98%. Rf¼0.61 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3228,
1436, 1221. 1H NMR (CDCl3, 250 MHz): 7.80 (m, 2H,
H–Ar); 7.50 (m, 3H, H–Ar); 2.00 (m, 2H, NH) 1.27 (s, 18H,
CH3). 31P NMR (CDCl3, 100 MHz) d ¼ 16.3 ppm. 13C NMR
(CDCl3, 100 MHz): 135.0; 131.5; 129.6; 128.6; 47.6; 29.1. MS
ESIþ 30 eV m/z: 269.2 [M þ H]þ 100% calcd for
1
tain sample H, 13C and 31P NMR and mass spectra for the
products 8 (supplementary information, Figures S1–S46).

6
F. BOUCHAREB ET AL.
[C14H25N2OP] 268. Anal. Calcd for C14H25N2OP: C 62.66, 2H, H–Ar); 6.23 (m, 2H, H–Ar); 6.17 (m, 2H, H–Ar); 4.00
H 9.39, N 10.44. Found: C 62.62, H 9.30, N 10.50%.
(m, 2H, NH). 31P NMR (CDCl3, 100 MHz) d ¼ 16.1 ppm.
13C NMR (CDCl3, 100 MHz): 162.9; 148.3;135.0; 131.5;
130.9; 129.6; 128.6; 110.7; 105.5. MS ESIþ 30 eV m/z: 345.1
[M þ H]þ 100% calcd for [C18H15 F2 N2OP] 344. Anal.
Calcd for C18H15F2N2OP: C 62.79, H 4.39, N 8.14. Found: C
62.75, H 4.35, N 8.24%.
Bis (piperidine) phenylphosphine oxide (8e)
Yield: 91%. Rf¼0.62 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 1591,
1456, 1211. 1H NMR (DMSO, 300 MHz): 7.60 (m, 2H,
H–Ar); 7.30 (m, 3H, H–Ar); 2.95 (t, J ¼ 10.05 Hz, 8H, CH2);
1.65 (m, 8H, CH2) 1.55 (m, 4H, CH2). 31P NMR (DMSO,
100 MHz) d ¼ 16.2 ppm. 13C NMR (DMSO, 100 MHz):
131.0; 130.7; 129.9; 128.1; 127.9; 127.8; 43.9; 22.5; 22.1. MS
ESIþ 30 eV m/z: 293.1 [M þ H]þ 100% calcd for
[C16H25N2OP] 292. Anal. Calcd for C16H25N2OP: C 65.73,
H 8.62, N 9.58. Found: C 65.70, H 8.59, N 9.60%.
Bis (4-chlorophenylamino) phenylphosphine oxide (8j)
Yield: 92%. Rf¼0.68 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3264,
1
1597, 1492, 1275. H NMR (CDCl3, 250 MHz): 7.90 (m, 2H,
H–Ar); 7.50 (m, 3H, H–Ar); 7.02 (m, 4H, H–Ar); 6.40 (m,
4H, H–Ar); 4.00 (m, 2H, NH). 31P NMR (CDCl3, 100 MHz)
d ¼ 16.4 ppm. 13C NMR (CDCl3, 100 MHz): 144.8; 135.0;
131.5; 129.7; 129.6; 128.6; 123.8; 116.5. MS ESIþ 30 eV m/z:
377.1 [M þ H]þ 100% calcd for [C18H15Cl2N2OP] 376. Anal.
Calcd for C18H15Cl2N2OP: C 57.32, H 4.01, N 7.43. Found:
C 57.39, H 4.10, N 7.40%.
Bis (morpholine) phenylphosphine oxide (8f)
Yield: 90%. Rf¼0.68 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 1457,
1200. 1H NMR (CDCl3, 250 MHz): 7.90 (m, 2H, H–Ar);
7.65 (m, 3H, H–Ar); 3.67 (t, J ¼ 8.45 Hz, 8H, CH2–O); 2.90
(t, J ¼ 7.30 Hz, 8H, CH2–N). 31P NMR (CDCl3, 100 MHz)
d ¼ 16.3 ppm. 13C NMR (CDCl3, 100 MHz): 135.0; 131.5;
129.6; 128.6; 72.8; 46.2. MS ESIþ 30 eV m/z: 297.2
[M þ H]þ 100% calcd for [C14H21N2O3P] 296. Anal. Calcs
for C14H21N2O3P: C 56.75, H 7.14, N 9.45. Found: C 56.70,
H 7.10, N 9.50%.
Bis (4-methylphenylamino) phenylphosphine oxide (8k)
Yield: 90%. Rf¼0.66 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3418,
1
1513,1436, 1279. H NMR (CDCl3, 250 MHz): 7.95 (m, 2H,
H–Ar); 7.55 (m, 3H, H–Ar); 6.81 (m, 4H, H–Ar); 6.34 (m,
4H, H–Ar); 4.00 (m, 2H, NH); 2.35 (s, 6H, CH3). 31P NMR
(CDCl3, 100 MHz) d ¼ 16.4 ppm. 13C NMR (CDCl3,
100 MHz): 143.7; 135.0; 131.5; 130.0; 129.6; 128.6; 127.7;
115.0; 20.9. MS ESIþ 30 eV m/z: 337.2 [M þ H]þ 100% calcd
for [C20H21N2OP] 336. Anal. Calcd for C20H21N2OP: C
71.41, H 6.29, N 8.33. Found: C 71.35, H 6.20, N 8.39%.
Bis (cyclohexylamino) phenylphosphine oxide (8g)
Yield: 97%. Rf¼0.62 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3155,
1461, 1250. 1H NMR (CDCl3, 250 MHz): 7.90 (m, 2H,
H–Ar); 7.50 (m, 3H, H–Ar); 3.15 (m, 2H, CH-cyc); 2.40 (m,
2H, NH); 1.90 (m, 4H, CH2-cyc); 1.65 (m, 4H, CH2-cyc);
1.15 (m, 12H, CH2-cyc). 31P NMR (CDCl3, 100 MHz)
d ¼ 16.5 ppm. 13C NMR (CDCl3, 100 MHz): 134.1; 132.4;
129.3; 55.2; 35.1; 25.2; 24.8. MS ESIþ 30 eV m/z: 321.1
[M þ H]þ 100% calcd for [C18H29N2OP] 320. Anal. Calcd
for C18H29N2OP: C 67.47, H 9.12, N 8.74. Found: C 67.50,
H 9.20, N 8.70%.
Bis (4-methoxyphenylamino) phenylphosphine oxide (8l)
Yield: 95%. Rf¼0.67 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3427,
1
1598, 1442, 1258. H NMR (CDCl3, 250 MHz): 7.90 (m, 2H,
H–Ar); 7.50 (m, 3H, H–Ar); 6.52 (m, 4H, H–Ar); 6.35 (m,
4H, H–Ar); 4.00 (m, 2H, NH) 3.73 (s, 6H, CH3). 31P NMR
(CDCl3, 100 MHz) d ¼ 16.4 ppm. 13C NMR (CDCl3,
100 MHz): 152.0; 139.0; 135.0; 131.5; 129.6; 128.6; 116.1;
114.9; 56.0. MS ESIþ 30 eV m/z: 369.2 [M þ H]þ 100% calcd
for [C20H21N2O3P] 368. Anal. Calcd for C20H21N2O3P: C
65.21, H 5.75, N 7.60. Found: C 65.25, H 5.80, N 7.57%.
Bis (phenylamino) phenylphosphine oxide (8h)
Yield: 94%. Rf¼0.67 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3223,
1
1599, 1499, 1293. H NMR (DMSO, 300 MHz): 7.95 (m, 2H,
H–Ar); 7.85 (m, 3H, H–Ar); 7.50 (m, 4H, H–Ar); 7.20 (m,
2H, H–Ar); 6.80 (m, 4H, H–Ar). 31P NMR (DMSO,
100 MHz) d ¼ 17.8 ppm. 13C NMR (DMSO, 100 MHz):
142.6; 132.1; 132.0; 129.2; 128.9; 128.8; 120.7; 118.2; 118.1.
MS ESIþ 30 eV m/z: 309.1 [M þ H]þ 100% calcd for
[C18H17N2OP] 308. Anal. Calcd for C18H17N2OP: C 70.12,
H 5.56, N 9.09. Found: C 70.10, H 5.51, N 9.19%.
Bis (2-methoxyphenylamino) phenylphosphine
oxide (8m)
Yield: 92%. Rf¼0.66 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3414,
1
1599, 1498, 1256. H NMR (CDCl3, 250 MHz): 7.95 (m, 2H,
H–Ar); 7.50 (m, 3H, H–Ar); 6.57 (m, 2H, H–Ar); 6.52 (m,
2H, H–Ar); 6.51 (m, 2H, H–Ar); 6.35 (m, 2H, H–Ar); 4.00
(m, 2H, NH) 3.73 (s, 6H, CH3). 31P NMR (CDCl3,
100 MHz) d ¼ 16.4 ppm. 13C NMR (CDCl3, 100 MHz): 148.6;
135.0; 132.3; 131.5; 129.6; 128.6; 121.6; 119.5; 116.1; 114.9;
Bis (3-fluorophenylamino) phenylphosphine oxide (8i)
Yield: 90%. Rf¼0.67 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3415, 56.0. MS ESIþ 30 eV m/z: 369.2 [M þ H]þ 100% calcd for
1
1529, 1494, 1279. H NMR (CDCl3, 250 MHz): 7.90 (m, 2H, [C20H21N2O3P]368. Anal. Calcd for C20H21N2O3P: C 65.21,
H–Ar); 7.50 (m, 3H, H–Ar); 6.99 (m, 2H, H–Ar); 6.33 (m, H 5.75, N 7.60. Found: C 65.25, H 5.80, N 7.57%.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
7
Bis (4-hydroxyphenylamino) phenylphosphine oxide (8n) 30 eV m/z: 447.1 [M þ H] þ 100% calcd for [C26H31N4OP]
446. Anal. Calcd for C26H31N4OP: C 69.94, H 7.00, N 12.55.
Found: C 69.99, H 7.09, N 12.50%.
Yield: 93%. Rf¼0.65 (CH2Cl2/MeOH). IR (KBr, cmꢀ1): 3175,
1
1511, 1468, 1247. H NMR (CDCl3, 250 MHz): 7.85 (m, 2H,
H–Ar); 7.45 (m, 3H, H–Ar); 6.48 (m, 4H, H–Ar); 6.29 (m,
4H, H–Ar); 5.10 (s, 1H, OH); 4.00 (m, 2H, NH). 31P NMR
Conclusion
(CDCl3, 100 MHz) d ¼ 16.3 ppm. 13C NMR (CDCl3,
We have successfully developed a simple, efficient, and
100 MHz): 147.3; 139.3; 135.0; 131.5; 129.6; 128.6; 116.5. MS
environmentally benign methodology toward the synthesis
of phosphonamides under ultrasonic techniques, but solvent
and catalyst-free conditions at room temperature. We
achieved the synthesis of phenyl phosphonamides derived
ESIþ 30 eV m/z: 341.1 [M þ H]þ 100% calcd for
[C18H17N2O3P] 340. Anal. Calcd for C18H17N2O3P: C 63.53,
H 5.04, N 8.23. Found: C 63.50, H 5.00, N 8.27%.
from amines with phenyl phosphonic dichloride in one step.
This methodology was established with many advantages,
including mild reaction conditions, short reaction times,
excellent yields, simple work-up procedures.
Bis (benzylamino) phenylphosphine oxide (8o)
Yield: 95%. Rf¼0.60 (CH2Cl2/MeOH). IR (KBr, cmꢀ1):
1
3163,1461, 1253. H NMR (CDCl3, 250 MHz): 7.90 (m, 2H,
H–Ar); 7.50 (m, 3H, H–Ar); 7.25 (m, 10H, H–Ar); 4.15 (m,
4H, CH2–N); 3.0 (m, 2H, NH). 31P NMR (CDCl3, 100 MHz) Disclosure statement
d ¼ 16.3 ppm. 13C NMR (CDCl3, 100 MHz): 140.0; 139.9;
No potential conflict of interest was reported by the author(s).
133.4; 131.9; 131.8; 131.7; 131.4; 128.7; 128.5; 127.7; 127.5;
127.3; 44.8. MS ESIþ 30 eV m/z: 337.2 [M þ H]þ 100% calcd
for [C20H21N2OP] 336. Anal. Calcd for C20H21N2OP: C
71.41, H 6.29, N 8.33. Found: C 71.47, H 6.33, N 8.30%.
Funding
This work was supported financially by The General Directorate for
Scientific Research and Technological Development (DG-RSDT),
Algerian Ministry of Scientific Research, Applied Organic Chemistry
Laboratory (FNR 2000).
Bis (phenylethylamino) phenylphosphine oxide (8p)
Yield: 94%. Rf¼0.63 (CH2Cl2/MeOH). IR (KBr, cm1): 3209,
1450, 1191. 1H NMR (CDCl3, 250 MHz): 7.75 (m, 2H,
H–Ar); 7.40 (m, 3H, H-Ar); 7.35–7.00 (m, 10H, H–Ar); 4.60
(m, 1H, CH); 4.35 (m, 1H, CH); 2.75 (s, 2H, NH); 1.5 (d,
J ¼ 6.25 Hz, 3H, CH3); 1.30 (d, J ¼ 6.77 Hz, 3H, CH3). 31P
NMR (CDCl3, 100 MHz) d ¼ 16.3 ppm. 13C NMR (CDCl3,
100 MHz): 145.2; 134.2; 132.1; 130.1; 128.8; 128.5; 126.9;
126.7; 55.4; 24.1. MS ESIþ 30 eV m/z: 365.1 [M þ H]þ 100%
calcd for [C22H25N2OP] 364. Anal. Calcd for C22H25N2OP:
C 72.51, H 6.91, N 7.69. Found: C 72.50, H 6.90, N 7.70%.
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