A novel, rapid and green method of phosphorylation under ultrasound irradiation and catalyst free conditions

Article abstract of DOI:10.1039/c5ra06380a

The phosphorylation reaction of various N-acylamines, N-acylaminoesters N-acylaminoalcohols and N-acylsulfonamides with trimethylphosphite or triethylphosphite was effectively promoted under ultrasound irradiation, solvent and catalyst free conditions to produce the corresponding amidophosponate. This rapid method produced the products in short reaction times (5-15 min) and excellent yields (75-90%). This technique at a frequency of 40 kHz, strongly accelerates the process of formation of P-C bonds compared to the classic Arbuzov reaction. This journal is

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A novel, rapid and green method of phosphorylation under ultrasound
irradiation and catalyst free conditions
Abdeslem Bouzina, Billel Belhani, Nour-Eddine Aouf, Malika Berredjem*
Received (in XXX, XXX) XthXXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
The phosphorylation reaction of various N-acylamines, Nꢀacylaminoesters Nꢀacylaminoalcohols and Nꢀ
acylsulfonamides with trimethylphosphite or triethylphosphite was effectively promoted under ultrasound
irradiation, solvent and catalyst free conditions to produce the corresponding amidophosponate. This
rapid method produced the products in short reaction times (5–15 min) and excellent yields (75–90%).
10 This technique at a frequency of 40 kHz, strongly accelerate the process of formation PꢀC bond compared
to the classic Arbuzov reaction.
Introduction
Amidophosponate have received considerable attention for
organic chemists,1ꢀ3 they are considered as an important class of
50 Results and discussion
15 compounds, with several interesting biological activities. Their
applications are significant in agriculture as plant regulators,
herbicides,4 pesticides and in medicine as anticancer agents,5
enzyme inhibitors,6 peptide mimics,7 antibiotics and
pharmacological agents.8 To the best of our knowledge, some
20 papers deal with amidophosponate structures.9–16 Several methods
have been described to introduce the phosphonate group, using
trialkylphosphite via Arbuzov reaction or under a variety of
conditions.17 Most of the methods reported above use expensive
catalysts, strong acidic conditions, and higher temperatures and
25 require longer reaction times. These include palladium complex
Pd(dba)2 or PdCl2 and PtBr2,18 room temperature imidazolium
ionic liquids, [Rmim][X].19 Besides, copper and nickelꢀcatalyzed
C–P coupling reactions have also been developed.20ꢀ21
We report here the application of the ultrasound induced
phosphorylation of N-acylamines, Nꢀacylaminoesters, N-
acylaminoalcohols and Nꢀacylsulfonamides, under catalystꢀfree
and solventꢀfree conditions. Thus, cavitation serves as a means of
55 concentrating the diffuse energy of sound to accelerate the
Arbuzov reaction. The process was promoted by directly
immersing of reaction vessels into the ultrasonic cleaning bath
which provides a fairly even distribution of energy into the
reaction medium.
60 The reaction was completed within 5ꢀ10 minutes (Scheme 1).
To synthesize organic substances efficiently in an artificial way,
30 it is required to develop convenient methods for forming carbonꢀ
phoshore bond. Under this situation, we tried to discover an
efficient novel CꢀP bond forming reactions by using ultrasound
irradiation.
Scheme 1Ultrasoundassisted phosphorylation of various
structurally Nꢀacylamines.
Therefore the development of new methods at moderate
35 temperature, milder reaction conditions, short reaction times and
better yields can possibly would extend the scope of the Arbuzov
reaction.
In continuation with our research on the synthesis of novel
phosphonate derivatives22ꢀ24 and in order to enlarge the
40 application of ultrasound irradiation25ꢀ26 in the synthesis of novel
compounds, we report herein a simple and efficient method for
the preparation of fully amidophosphonate under ultrasound
irradiation (scheme 1, 2, 3 and 4).
65 The results are summarized in (Table 1, entry 1aꢀ4a). This is an
efficient and environmentally benign methodology for the
synthesis of αꢀamidophosphonate at 90°C temperatures. This
reaction was established with many advantages, including simple
workꢀup procedures, short reaction times and excellent yields.
70
45
75
Table1Phosphorylation of Nꢀacylamines under ultrasound irradiation
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Entry
Substrat
Product
Time (min)
Yield (%)
1a
8
6
90
2a
89
3a
4a
10
12
84
86
To increase the scope of this reaction, we attempted the
phosphorylation to Nꢀacylaminoesters synthesized from primary
amino acid esters (Scheme 2). The isolated yields of products
(Table 2, entry 1b–3b) were in the range of 80–88 % after 10ꢀ15
minutes of reaction..
5
Scheme 2 Ultrasound assisted phosphorylation of various
structurally Nꢀacylaminosters.
10 Table 2 Phosphorylation of Nꢀacylaminoesters under ultrasound irradiation
Entry
Substrat
Product
Time (min)
10
Yield (%)
OMe
O
O
Cl
1b
80
N
H
2b
3b
12
15
82
88
15 The mildness of this procedure was next illustrated by arrange of
Nꢀacylaminoalcohols (Scheme 3) (Table 3, entries 1c–3c), the
reaction worked very well.
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Scheme 3 Ultrasound assisted phosphorylation of various
structurally Nꢀacylaminoalcohols.
Table 3 Phosphorylation of Nꢀacylaminoalcohols sunder ultrasound irradiation
Entry
1c
Substrat
Product
Time (min)
10
Yield (%)
79
75
83
2c
3c
15
12
5
Encouraged by the preliminary result and to increase the scope of
this reaction, we extended this study to Nꢀacylsulfonamides
(Scheme 3). The Nꢀacylsulfonamides were prepared starting from
chlorosulfonylisocyanate (CSI), primary amine in three steps
O
O
O
O
O
O
AlCl3
S
Cl
+
S
R
Cl
N
H
N
H
R
N
H
NH2
Toluene, r.t
Cl
))) 40 KHz
5-15 min
90°, neat
10 (carbamoylationꢀsulfamoylation, deprotection and acylation).27
The results are summarized in (Table 4, entry 1dꢀ6d).
P(OMe)3
O
O
O
O
S
R= Aryl, Alkyl
P
OMe
OMe
R
N
H
N
H
Scheme 4Ultrasound assisted phosphorylation of various
structurally Nꢀacylsulfonamides.
15 Table 4Phosphorylation of Nꢀacylsulfonamide s under ultrasound irradiation
Entry
Substrat
Product
Time (min)
10
Yield (%)
85
1d
2d
3d
5
90
80
10
4d
10
83
5d
6d
15
5
88
75
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This work was supported financially by The General Directorate
for Scientific Research and Technological Development (DGꢀ
50 RSDT), Algerian Ministry of Scientific Research, Applied
Organic ChemistryLaboratory (FNR 2000). We also thank Mr.
Jacques Lebreton Professor at University of Nantes for his help in
the identification for all products in NMR and MS.
Experimental
1. General:
All chemicals and solvents were purchased from common
commercial sources and were used as received without any
further purification. All reactions were monitored by TLC on
silica Merck 60 F254 percolated aluminum plates and were
developed by spraying with ninhydrin solution. Column
chromatography was performed with Merck silica gel (230ꢀ400
mesh). Proton nuclear magnetic resonance (1H NMR) spectra
5
Notes and references
55 aLaboratory of Applied Organic Chemistry, Synthesis of biomolecules and
molecular modelling Group, Sciences Faculty, Chemistry Department,
Badji-Mokhtar - Annaba University, Box 12, 23000 Annaba, Algeria.
*Corresponding author. Email: malika.berredjem@univ-annaba.org
† Spectral data for the synthesis of Nꢀacylamines, Nꢀacylaminoesters, Nꢀ
60 acylaminoalcoholsandNꢀacylsulfonamides,prepared in this work are
available in the supporting information joined to this manuscript.
10 were recorded on a Brücker spectrometer at 250, 300 or 400
MHz. Chemical shifts are reported in δ units (ppm) with TMS as
reference (δ 0.00). All coupling constants (J) are reported in
Hertz. Multiplicity is indicated by one or more of the following: s
15 (singlet), d (doublet), t (triplet), q (quartet), m (multiplet). Carbon
nuclear magnetic resonance (13CNMR) spectra were recorded on
a Brücker at 60, 75 or 100 MHz. Chemical shifts are reported in δ
units (ppm) relative to CDCl3 (δ 77.0). Infrared spectra were
recorded on a SHIMADZU FTꢀIR 8000 spectrometer. Elemental
20 analysis was recorded on a EURO E.A 3700. Melting points were
recorded on a Büchi Bꢀ545 apparatus in open capillary tubes.
1
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Acids, Chemistry and Biological Activity, V.P. Kukhar, H.R. Hudson,
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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 reactions were carried out in an
25 open glass tube (diameter: 25 mm; thickness: 1 mm; volume: 20
mL) at 90°.
S. Laschat, and H. Kunz, Synthesis., 1992, 90.
2. Typical experimental procedure for the phosphorylation
80 10 J. Pol. Zou, J. Chem., 1981, 55, 643.
In a 10 ml round bottom flask taken a mixture of Nꢀ
acylsulfonamide (1 mmol) with triethylphosphite or
30 trimethylphosphite (1 mmol) was added. Then reaction mixture
was subjected to the ultrasonication for appropriate time. After
completion of the reaction, as indicated by TLC, silica gel;
dichloromethane:methanol (9,5:0.5),
11 A. Heydari, A. Karimian and J. Ipaktschi, Tetrahedron Lett., 1998,
39, 6729.
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Surplus reactants were removed by column chromatography
35 eluted with dichloromethane.
90
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Mohanakrishnan, Org. Lett., 2011, 13, 1270.
In conclusion, a simple, efficient, and environmentally benign
methodology towards the synthesis of αꢀamidophosponate has
been reported. The use of ultrasound irradiation as an effective
40 basic promoter supports the practical utility of this procedure for
a wide variety of substrates. Further studies to develop new clean
methodology towards the synthesis of biologically active
compounds are in progress.
The effect of ultrasound has mostly been shown by increasing the
45 yields of reactions and in some cases the ratio of formed
products.
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Acknowledgements
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A novel, rapid and green method of phosphorylation under
ultrasound irradiation and catalyst free conditions
Abdeslem Bouzina, Billel Belhani, Nour-eddine Aouf, Malika Berredjem*,
Abstract
The phosphorylation reaction of various N-acylamines, N-acylaminoesters N-
acylaminoalcohols and N-acylsulfonamides with trimethylphosphite or triethylphosphite was
effectively promoted under ultrasound irradiation, solvent and catalyst free conditions to
produce the corresponding amidophosponate. This rapid method produced the products in
short reaction times (5–15 min) and excellent yields (75–90%). This technique at a frequency
of 40 kHz, strongly accelerate the process of formation P-C bond compared to the classic
Arbuzov reaction.
O
O
P
O
R
R
Cl
OMe
OMe
N
N
H
R
H
O
HN
OMe
OMe
S
H
H
N
O
P
O
HN
N
O
O
Cl
O
OEt
OEt
R
O
O
R
O
P
OR1
P
MeO
OH
H
N
MeO
OH
+
O
H
R1O
OR1
N
P
OEt
Cl
R
OEt
O
R
O
O
HN
R
O
O
S
O
O
O
O
P
HN
O
O
O
Solvent free
catalyst free
R
S
OMe
OMe
R
S
Cl
N
N
Cl
N
H
N
H
+
OHMe
P
H
H
OMe
OMe
Ultrasound irradiation
40 KHz, 90°