A facile and clean procedure for preparation of -aminophosphonates via a rotary evaporator equipped with circulating water vacuum pumps

Article abstract of DOI:10.1080/10426500903023095

RE-CWVP (rotary evaporator equipped with a circulating water vacuum pump)-assisted synthesis is reported as an extremely efficient, facile, and clean procedure for the preparation of -aminophosphonates in organic synthesis and industrial processes. The title -aminophosphonates are obtained in good to satisfactory yields by the method and characterized by means of IR, 1H NMR, 31P NMR, 13C NMR, and mass spectrometry.

Full text of DOI:10.1080/10426500903023095

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A Facile and Clean Procedure for
Preparation of α-Aminophosphonates
via a Rotary Evaporator Equipped with
Circulating Water Vacuum Pumps
Zhiyu Ju a b , Ruyi Zou a , Yong Ye a c & Yufen Zhao a c
a Key Laboratory of Chemical Biology and Organic Chemistry of
Henan Province, Department of Chemistry , Zhengzhou University ,
Zhengzhou, China
b College of Chemistry and Chemical Engineering , Xuchang
University , Xuchang, China
c Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical
Biology (Ministry of Education), Department of Chemistry , Tsinghua
University , Beijing, China
Published online: 23 Mar 2010.
To cite this article: Zhiyu Ju , Ruyi Zou , Yong Ye & Yufen Zhao (2010) A Facile and Clean Procedure
for Preparation of α-Aminophosphonates via a Rotary Evaporator Equipped with Circulating Water
Vacuum Pumps, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:4, 898-902, DOI:
10.1080/10426500903023095
To link to this article: http://dx.doi.org/10.1080/10426500903023095
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Phosphorus, Sulfur, and Silicon, 185:898–902, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903023095
A FACILE AND CLEAN PROCEDURE FOR PREPARATION
OF α-AMINOPHOSPHONATES VIA A ROTARY
EVAPORATOR EQUIPPED WITH CIRCULATING WATER
VACUUM PUMPS
Zhiyu Ju,1,2 Ruyi Zou,1 Yong Ye,1,3 and Yufen Zhao1,3
1Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province,
Department of Chemistry, Zhengzhou University, Zhengzhou, China
2College of Chemistry and Chemical Engineering, Xuchang University,
Xuchang, China
3Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology
(Ministry of Education), Department of Chemistry, Tsinghua University,
Beijing, China
RE-CWVP (rotary evaporator equipped with a circulating water vacuum pump)–assisted
synthesis is reported as an extremely efficient, facile, and clean procedure for the prepa-
ration of α-aminophosphonates in organic synthesis and industrial processes. The title
α-aminophosphonates are obtained in good to satisfactory yields by the method and charac-
terized by means of IR, 1H NMR, 31P NMR, 13C NMR, and mass spectrometry.
Keywords α-Aminophosphonates; clean synthesis; flame retardants; Mannich-type reaction
INTRODUCTION
In the 1970s, Pyrovatex CP (N-hydroxymethyl-3-(dimethoxy-phosphoryl)propana
mide) was successfully applied as a durable flame retardant to modify pure cotton fabric.1
But it is a fatal defect that formaldehyde is easily released during industrial processes
and use.2 On 15 June 2004, a panel of the World Health Organization from 10 countries
announced in its conclusions that formaldehyde poses a greater hazard than previously
thought.3 They noted that the chemical is “carcinogenic to humans.” Thus, to a large extent,
its application is restricted for some uses.2,4 In addition, the processes for the synthesis of
industrially important flame retardants require the use of many harmful organic solvents,
chemicals, and catalysts,5 and many of these processes consist of a number of steps that
are neither environmental friendly nor economical. Therefore, we attempted to develop
alternative flame retardants for cotton fabrics that are synthesized by a Mannich-type
reaction, as shown in Scheme 1.
Received 15 December 2008; accepted 6 May 2009.
The authors would like to thank the National Natural Science Foundation of China (Nos. 20602032,
20732004, and 20572061) for financial support.
Address correspondence to Yong Ye and Yufen Zhao, Department of Chemistry, Key Laboratory
of Chemical Biology and Organic Chemistry, Zhengzhou University, Zhengzhou 450052, China. E-mail:
juz1696@yahoo.com.cn
898

PREPARATION OF α-AMINOPHOSPHONATES
899
O
P
O
RO
RO
OH
RE-CWVP
OH
RO
RO
+ PhCHO +
H
+ H2O
H2N
P
N
H
a~d
R= Me, Et, n-Pr, i-Bu
Scheme 1 Synthetic route of α-aminophosphonates containing a hydroxyl group.
Generally, transformations of the Mannich-type reaction could be fulfilled under
the catalysis of Bro¨nsted6 or Lewis acids such as BF3/Et2O,7 ZnCl2,8 MgBr2,8 or SnCl4.6
However, these methods have limitations, as many imines are hygroscopic and are not
sufficiently stable for isolation. The first one-pot synthesis of α-aminophosphonates has
been achieved by the reaction of phosphite with imines in the presence of lanthanide triflate9
as the catalyst in organic solvent, and has been generated in situ from aldehydes and amines.
Subsequently, one-pot variations in organic solvents have been improved.10–18 Recently, it
was reported that solvent-free transformations of phosphites to α-aminophosphonates could
be accomplished in the presence of acidic catalysts19 using microwave-assisted methods.20
All of the above preparation procedures are uneconomical, however, because they are
require a certain amount of catalyst, whether or not an organic solvent is needed.
In this article we report a clean and facile procedure for the solvent-free and catalyst-
free preparation of α-aminophosphonates containing an active hydroxyl group by rotary
evaporator equipped with a circulating water vacuum pump (RE-CWVP) as a preparation
tool.
RESULTS AND DISCUSSION
The preparation of the compounds a and b have been reported previously,20,21 but
complete spectroscopic data for them have not yet appeared. Therefore, in this article, we
shall not only supplement their spectroscopic data but also report a cleaner and more facile
preparation procedure compared with the previous synthetic methods.
Experimental Principle
A reverse reaction can occur if the water released by a Mannich-type reaction is not
separated from the reaction system. For that reason, we employ circulating water vacuum
pumps (CWVP) that can continuously suck water out of the vessel through the valve of a
circulating water vacuum pump equipment to shift the equilibrium to the right, namely, to
shift the equilibrium to the target product.
In order to further reduce the effect of the solvent pollution on CWVP, the ethanol is
cooled by low-temperature cooling liquid circulating pumps and then carried in the cooling
circulating system for rotary evaporator.
Effects of the Factors on Synthesis of α-Aminophosphonates
Taking the compound a as an example below, we discuss carefully the influence
of the three factors, i.e., the reaction temperature, the reaction time, and RE-CWVP on
preparation of α-aminophosphonates.

900
Z. JU ET AL.
with RE-CWVP
without RE-CWVP
80
70
60
50
40
30
20
10
0
20
40
60
80
100
Time (Minutes)
Figure 1 Both yields of different reaction time for the compound a with and without RE-CWVP (solvent-free,
temperature at 70◦C).
When the reaction temperature reaches 75◦C, the viscous solvent changes quickly
into a white solid within a few minutes. The mixture was checked by TLC to observe five
new spots and recorded by ESI-MS. When the reaction occurs at 65◦C, the yield of the
compound a is about 60% in 2 h. However when the temperature rises to 70◦C, a satisfactory
yield (77%) is obtained in a short time (30 min). Prolonged time at that temperature keeps
its yield almost constant (shown in Figure 1). Therefore, the optimal conditions should be
at 70◦C for 30 min.
Compared with an experiment without using RE-CWVP under the same conditions.
(Figure 1), the yield of the compound a is only 30% at 30 min. However, it is approximately
40% for a prolonged time (60 min), which demonstrates that RE-CWVP is an extremely
efficient and facile device for the preparation of α-aminophosphonates containing an active
hydroxyl group.
Hence the one-pot synthesis for α-aminophosphonates containing an active hydroxyl
group has optimized reaction conditions of 30 min at 70◦C under solvent-free and catalyst-
free conditions for benzaldehyde, monoethanolamine, and dialkyl phosphite operated by
RE-CWVP.
CONCLUSION
The common RE-CWVP is an extremely efficient, facile, and clean reaction device
for the preparation of α-aminophosphonates containing an active hydroxyl group, which
displays not only environmentally friendly methods and economy, but also a convenient
operation. The corresponding α-aminophosphonates are obtained under solvent-free and
catalyst-free conditions in satisfactory yields. Title compounds are characterized by IR, 1H
NMR, 31P NMR, 13C NMR, and mass spectrometry.

PREPARATION OF α-AMINOPHOSPHONATES
901
EXPERIMENTAL
All chemicals and materials were of analytical grade, and all solutions were freshly
dried by standard methods.
1H NMR spectra and 13C NMR were obtained on a Bruker Advance DMX 400 MHz
instrument using TMS as internal standard in CDCl3. 31P NMR spectra were obtained on
a Bruker Advance DMX 400 spectrometer at 162 MHz, and the chemical shifts values
were referenced to 85% H3PO4 as an external reference. Chemical shifts were reported in
δ ppm. FT-IR spectra were recorded on a Nicolet Avatar spectrophotometer. Mass spectra
were recorded on a Bruker Esquire 3000 ion trap mass spectrometer. RE-52AA-type rotary
evaporator equipped with circulating water vacuum pumps was purchased from Shanghai
Yarong Biochemical Instrument Factory, China. DLSB-4/10-type low-temperature cooling
liquid circulating pump was produced by Gongyi Yingyu Instrument Factory, China.
General Procedure
At a temperature of 70◦C (water bath temperature) and vacuum of 0.09 MPa, a
mixture of benzaldehyde (5 mmol), monoethanolamine (5 mmol), and dialkyl phosphite
(5.25 mmol) was rotated and heated by rotary evaporator for 30 min (checked by TLC).
After the reaction was complete, the mixture was isolated by gel chromatography with ethyl
acetate:alcohol (3:1) as the eluent to afford the target products as colorless viscous liquids.
All products were characterized by NMR, IR, and mass spectral data, and the complete
spectroscopic data are given below.
1
Compound a: Yield: 77%. H NMR: 7.32∼7.43 (m, 5H, C6H5), 4.07 (d, 1H, CH,
2
2
2JPH = 20.5 Hz), 3.76(d, 3H, CH3, JPH = 8.3 Hz), 3.53 (d, 3H, CH3, JPH = 8.3 Hz),
3.55∼3.74 (m, 2H, CH2OH), 2.63∼2.79 (m, 2H, CH2N), 2.11 (br, 2H); 31P NMR: 25.71;
13C NMR: 135.58, 128.69, 128.35, 128.18, 61.50, 59.38, 53.59, 49.41; IR(KBr)(cm−1):
3200∼3500, 3028, 2954, 2852, 1637, 1603, 1455, 1400, 1242, 1055; ESI-MS: m/z 259.8
[M+H]+.
1
Compound b: Yield: 80%. H NMR: 7.31∼7.43 (m, 5H, C6H5), 4.10 (d, 1H, CH,
2JPH = 20.5 Hz), 4.12 (m, 2H, CH2O), 3.64 (m, 2H, CH2O), 3.76∼3.97 (m, 2H, CH2OH),
2.65∼2.77 (m, 2H, CH2N), 2.09 (br, 2H), 1.31 (t, 3H, CH3, 3J = 7.3 Hz), 1.14 (t, 3H, CH3,
3J = 7.3 Hz); 31P NMR: 23.44; 13C NMR: 135.87, 128.55, 128.41, 128.02, 62.87, 61.10,
59.66, 49.44, 16.35; IR(KBr)(cm−1): 3200∼3500, 3030, 2985, 2932, 1638, 1493, 1454,
1397, 1238, 1053, 1026; ESI-MS: m/z 287.9 [M+H]+.
1
Compound c: Yield: 81%. H NMR: 7.30∼7.43 (m, 5H, C6H5), 4.05 (d, 1H, CH,
2JPH = 20.5 Hz), 4.00 (m, 2H, CH2O), 3.65∼3.84 (m, 2H, CH2OH), 3.60 (m, 2H, CH2O),
2.67∼2.77 (m, 2H, CH2N), 1.67 (m, 2H, CH2CH3), 1.50 (m, 2H, CH2CH3), 2.06 (br, 2H),
0.93 (t, 6H, CH3, 3J = 7.3 Hz), 0.81 (t, 3H, CH3, 3J = 7.3 Hz); 31P NMR: 23.29; 13C NMR:
135.98, 128.52, 128.41, 128.00, 68.30, 60.05, 59.61, 49.43, 23.84, 9.94; IR(KBr)(cm−1):
3200∼3500, 3030, 2969, 1636, 1460, 1399, 1237, 1061, 1001; ESI-MS: m/z 316.0 [M+H]+.
1
Compound d: Yield: 83%. H NMR: 7.34∼7.41 (m, 5H, C6H5), 4.05 (d, 1H, CH,
2JPH = 20.5 Hz), 3.81 (m, 2H, CH2O), 3.46∼3.80 (m, 2H, CH2OH), 3.42 (m, 2H, CH2O),
2.65∼2.79 (m, 2H, CH2N), 2.06 (br, 2H), 1.92 (s, H, CH), 1.75 (s, H, CH), 0.91 (s, 12H,
CH3); 31P NMR: 23.02; 13C NMR: 135.07, 128.48, 128.40, 127.94, 69.63, 60.03, 59.62,
49.49, 29.18, 18.65; IR(KBr)(cm−1): 3200∼3500, 2962, 2868, 1650, 1593, 1470, 1401,
1240, 1045, 1013; ESI-MS: m/z 344.0 [M+H]+.

902
Z. JU ET AL.
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