A novel and efficient synthesis of α-aminophosphonates by use of triphenyl phosphite in acetic acid media

Article abstract of DOI:10.1080/10426507.2010.500641

Chemical Equation Presented For the first time, α-aminophosphonates were obtained by a simple and efficient one-pot method from the reaction between aldehyde, aniline, and triphenyl phosphite in the presence of acetic acid as a catalyst and solvent at roo

Full text of DOI:10.1080/10426507.2010.500641

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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A Novel and Efficient Synthesis of α-
Aminophosphonates by Use of Triphenyl
Phosphite in Acetic Acid Media
Mohsen Rostamizadeh a , Malek Taher Maghsoodlou a , Nourallah
Hazeri a , Sayyed Mostafa Habibi-khorassani a & Leila Keishams b
a Department of Chemistry , The University of Sistan and
Baluchestan , Zahedan, Iran
b Central Laboratory , Shahid Chamran University , Ahvaz, Iran
Published online: 19 Feb 2011.
To cite this article: Mohsen Rostamizadeh , Malek Taher Maghsoodlou , Nourallah Hazeri ,
Sayyed Mostafa Habibi-khorassani & Leila Keishams (2011) A Novel and Efficient Synthesis of α-
Aminophosphonates by Use of Triphenyl Phosphite in Acetic Acid Media, Phosphorus, Sulfur, and
Silicon and the Related Elements, 186:2, 334-337, DOI: 10.1080/10426507.2010.500641
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Phosphorus, Sulfur, and Silicon, 186:334–337, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.500641
A NOVEL AND EFFICIENT SYNTHESIS OF
α-AMINOPHOSPHONATES BY USE OF TRIPHENYL
PHOSPHITE IN ACETIC ACID MEDIA
Mohsen Rostamizadeh,1 Malek Taher Maghsoodlou,1
Nourallah Hazeri,1 Sayyed Mostafa Habibi-khorassani,1
and Leila Keishams2
1Department of Chemistry, The University of Sistan and Baluchestan,
Zahedan, Iran
2Central Laboratory, Shahid Chamran University, Ahvaz, Iran
GRAPHICAL ABSTRACT
O
(PhO)2P
Ar
O
CH3COOH
R.T 12-48 h
+
H
+
P(OPh)3
Ph NH2
Ph
N
H
Ar
Abstract For the first time, α-aminophosphonates were obtained by a simple and efficient
one-pot method from the reaction between aldehyde, aniline, and triphenyl phosphite in the
presence of acetic acid as a catalyst and solvent at room temperature.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Keywords Acetic acid; α-aminophosphonates; multicomponent reaction; triphenyl phosphite
INTRODUCTION
In recent years, there has been increasing interest in the synthesis of organophospho-
rus compounds. This is due to the value of such compounds that have biological effects
and medicinal importance (enzyme inhibitors,1 HIV protease,2 antibiotics,3 herbicides,
fungicides, insecticides,4 plant growth regulators,5 and antithrombotic agents,6 as well as
peptidases and proteases).7 Thus a variety of synthetic approaches for the synthesis of α-
aminophosphonates is desirable. Among the available methods, the nucleophilic addition
Received 9 April 2010; accepted 2 June 2010.
The authors sincerely thank the University of Sistan & Baluchestan for providing financial support for this
work.
Address correspondence to Malek Taher Maghsoodlou, Department of Chemistry, The University of Sistan
and Baluchestan, P.O. Box 98135-674, Zahedan, Iran. E-mail: mt maghsoodlou@yahoo.com
334

SYNTHESIS OF α-AMINOPHOSPHONATES
335
O
(PhO)2P
O
CH3COOH
+
H
+
P(OPh)3
Ph NH2
Ph
R.T
12-48 h
Ar
N
H
Ar
1
2
3
4
Figure 1 Synthesis of α-aminophosphonates.
of phosphites to imines is the most convenient and is usually activated by Lewis acids in-
cluding lantanide triflate,8 samarium diiodide,9 InCl3,10 TaCl5–SiO2,11 bromodimethylsul-
fonium bromide,12 LiClO4,13 montmorillonite KSF,14 ZrCl4,15 alumina-supported reagents
as catalysts,16 Amberlite-IR 120,17 H3PW12O40,18 oxalic acid,19 and TiO2,20 and generally
dialkyl or trialkyl phosphites were used as phosphorus reagents. However, there is no re-
port for the synthesis of α-aminophosphonates using triaryl phosphite as a reagent. We
now describe a mild and efficient protocol for the synthesis of α-aminophosphonates using
triphenyl phosphite in acetic acid as solvent and catalyst at room temperature (Figure 1).
RESULTS AND DISCUSSION
In the current work, initially benzaldehyde was used to react with aniline and triphenyl
phosphite in the presence of acetic acid as both solvent and catalyst at room temperature to
give the corresponding α-aminophosphonate in 98% yield.
In addition, several aldehydes were employed in a series of experiments for generation
of the other corresponding α-aminophosphonates in high to excellent yields. The results
are summarized in Table 1.
The structures of compounds 4a–p were deduced from IR, 1H NMR, 13C NMR, 31
P
NMR, and mass spectra, and elemental analyses. Compounds 4a–p are chiral, but racemic
mixtures were obtained because both the reactants and the reaction medium were achiral. In
Table 1 Preparation of α-aminophosphonates
Entry
Ar
Product
Yielda (%)
Mp (◦C)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Phenyl
2-Nitrophenyl
3-Nitrophenyl
4-Nitrophenyl
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
98
82
90
85
80
83
88
80
85
83
91
65
80
84
80
85
134–136
137–139
128–129
147–149
126–128
130–132
136–138
123–125
117–119
119–121
103–105
110–112
115–117
114–116
125–127
124–126
3-Chlorophenyl
4-Chlorophenyl
2,4-Dichlorophenyl
2,6-Dichlorophenyl
2-Fluorophenyl
3-Fluorophenyl
4-Fluorophenyl
2,3-Dimethoxyphenyl
2,5-Dimethoxyphenyl
2-Methylphenyl
3-Methylphenyl
4-Methylphenyl
aYields refer to the pure isolated products.

336
M. ROSTAMIZADEH ET AL.
summary, we have efficiently prepared novel α-aminophosphonates by a one-pot reaction
between triphenyl phosphite, various aromatic aldehydes, and aniline in the presence of
acetic acid at room temperature.
EXPERIMENTAL
Melting points and IR spectra were measured on an Electro thermal 9100 apparatus
1
and a Shimadzu IR-460 spectrometer, respectively. H, 13C, and 31P NMR spectra were
measured on a Bruker DRX-400 Avance spectrometer with CDCl3 as solvent. Elemen-
tal analyses for C, H, and N were performed using a Heraeus CHN-O-Rapid analyzer.
Mass spectra were recorded on an Agilent Technology (HP) spectrometer operating at an
ionization potential of 70 eV.
Synthesis of α-Aminophosphonates: General Procedure
A mixture of aromatic aldehyde (1 mmol), aniline (1 mmol), and triphenyl phosphite
(1 mmol) in acetic acid (5 mL) was stirred at room temperature for the appropriate time
(12–48 h). After completion of the reaction (as indicated by TLC), the solution was filtered,
and the solid phase (product) was washed with water to afford pure α-aminophosphonates.
In the case that the α-aminophosphonate was soluble in acetic acid, water was added to
the solution and the mixture was extracted with CH2Cl2. The organic layer was dried over
anhydrous Na2SO4, the solvent was removed under reduced pressure, and the generated
precipitate was washed with cold diethyl ether to afford pure α-aminophosphonates.
Complete physical and spectroscopic data for compounds 4a–p can be found online
in the Supplemental Materials.
Selected Data for Compound 4o
1
White crystals, mp 125–127◦C. IR (KBr) (υmax, cm−1): 3342 (NH). H NMR (400
2
MHz): δ 2.35 (3H, s, CH3), 4.79 (1H, bs, NH), 5.17 (1H, d, JHP = 24.6 Hz, CHP),
6.71–7.41 (19H, m, aromatic). 13C NMR (100.6 MHz) δ: 21.46 (s, CH3), 55.96 (d, 1JCP
=
153.9 Hz, CHP), 114.20 (s, 2 Cortho, NHPh), 118.95 (s, Cpara, NHPh), 120.36, 120.75 (2d,
3JCP = 4.3 Hz, 4 Cortho, 2 OPh), 125.24, 125.39 (2s, 2 Cpara, 2 OPh), 125.41 (s, C4), 128.71
(d, 3JCP = 2.1 Hz, C6), 128.95 (d, 3JCP = 6.2 Hz, C2), 129.25 (s, C5), 129.29 (s, 2 Cmeta
,
NHPh), 129.61, 129.76 (2s, 4 Cmeta, 2 OPh), 134.40 (s, C3), 138.51 (d, 2JCP = 2.5 Hz, C1),
3
2
145.63 (d, JCP = 14.7 Hz, Cipso, NHPh), 150.29, 150.40 (2d, JCP = 10.1 Hz, 2 Cipso, 2
OPh). 31P NMR (161.97 MHz) δ: 15.51. MS m/z (%): 429 (17) [M+], 196 (100), 178 (15),
140 (20), 104 (34), 77 (42). Anal. Calcd for C26H24NO3P: C, 72.72; H, 5.63; N, 3.26%.
Found: C, 72.51; H, 5.70; N, 3.39%.
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