Synthesis of α-aminophosphonates under conditions of phase-transfer catalysis

Article abstract of DOI:10.1023/A:1016530718938

An easy preparative synthesis of α-aminophosphonates by reaction of azomethines with diethyl phosphite under conditions of phase-transfer catalysis was developed.

Full text of DOI:10.1023/A:1016530718938

Russian Journal of Organic Chemistry, Vol. 38, No. 4, 2002, pp. 484 486. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 4, 2002,
pp. 508 510.
Original Russian Text Copyright
2002 by Kabachnik, Ternovskaya, Zobnina, Beletskaya.
Synthesis of -Aminophosphonates under Conditions
of Phase-transfer Catalysis
M. M. Kabachnik, T. N. Ternovskaya, E. V. Zobnina, and I. P. Beletskaya
Lomonosov Moscow State University, Moscow, 119899 Russia
Received August 17, 2001
Abstract An easy preparative synthesis of -aminophosphonates by reaction of azomethines with diethyl
phosphite under conditions of phase-transfer catalysis was developed.
Among various organophosphorus compounds
prepared with the use of phase-transfer catalysis
(PTC), the most numerous are phosphonates and
-hydroxyphosphonates [1 3]. Yet the -amino-
phosphonates have not been synthesized under PTC
conditions.
The reaction was carried out in benzene or THF at
the reagents ratio 1: 1 in the presence of tetrabutyl-
ammonium iodide (TBAI, 5 mol%) as a phase-trans-
fer catalyst. As bases were tested K2CO3, Cs2CO3,
and KF. The reaction progress was monitored by IR
and 31P NMR spectroscopy. The conditions of the
reaction under study (time, temperature, amount of
the base used) are listed in Table 1. There are also
given the yields of separated -aminophosphonate Ia.
We for the first time carried out a synthesis of
-aminophosphonates under PTS conditions. The
reaction conditions were developed using as an
example reaction between O,O-diethyl phosphite and
N-cyclohexylbutyralimine.
As seen from Table 1, the optimum conditions of
the reaction under study require the use of double
excess of K2CO3, 5.5 mol% of TBAI, heating to 40
45 C for 5 h.
Under the PTC conditions the reaction readily
occurs both at slight heating (40 45 C) and at room
temperature; the latter is especially important for the
synthesis of -aminophosphonates of the natural
structure.
Under the conditions developed we prepared a
number of -aminophosphonates Ia g in 74 80%
yield.
Table 1. Conditions of reaction between O,O-diethyl
phosphite and N-cyclohexylbutyralimine in benzene
(phase-transfer catalyst TBAI, 5 mol%)
Base:diethyl Tempera-
Yield after
separation,
%
Time,
h
Base
phosphite
ratio
ture, C
K2CO3
1: 1
2: 1
20
20
8
8
61
58
K2CO3/
NaHCO3
Cs2CO3
KFa
K2CO3
K2CO3
I, R1 = H, R2 = Pr, R3 = cyclo-C6H11 (a); R1 = H,
R2 = Pr, R3 = t-Bu (b); R1 = H, R2 = Ph, R3 =
cyclo-C6H11 (c); R1 = H, R2 = Ph, R3 = Ph (d); R1 =
H, R2 = 2-Fu, R3 = t-Bu (e); R1 = H, R2 = 3-Py,
R3 = Ph (f); R1 = Me, R2 = Et, R3 = cyclo-C6H11 (g).
1: 1
1: 1
2: 1
2: 1
2: 1
2: 1
20
20
20
40 45
40 45
40 45
6
8
6
5
6
8
64
<10
64
80
70
K2CO3/Et3N
K2CO3b
Physico-chemical constants, yields, 31P and
1H NMR spectral data, and elemental analyses of
-aminophosphonates Ia g are given in Tables 2, 3.
72
b
a Reaction was performed in THF. With no catalyst.
1070-4280/01/3804-484$27.00 2002 MAIK Nauka/Interperiodica

SYNTHESIS OF -AMINOPHOSPHONATES
485
Table 2. Yield, boiling and melting points, and some spectral data of compounds Ia g
bp,
C
31P NMR
Compd.
no.
Yield,
%
(p, mm Hg), spectrum,
mp,
1H NMR spectrum (CDCl3), , ppm
C
, ppm
29.05
Ia
Ib
Ic
80
77
74
79
76
108 110 (10)
70 (15)
124 (8)
90 91
0.98 s (3H, CH3CH2CH2), 1.1 m (11H, C6H11-cyclo), 1.24 t (6H,
CH3CH2O), 1.42 m (2H, CH3CH2CH2), 1.78 m (2H, CH3CH2CH2),
2.82 m (1H, CHP, J 17 Hz), 4.10 q (4H, CH3CH2O)
0.87 s (3H, CH3CH2CH2), 1.04 s [9H, C(CH3)3], 1.26 t (6H,
29.09
25.30
22.92
21.61
CH3CH2O), 1.45
m (2H, CH3CH2CH2), 1.68 m (2H,
CH3CH2CH2), 2.86 m (1H, CHP, J 17Hz), 4.06 q (4H, CH3CH2O)
1.12 m (11H, C6H11-cyclo), 1.28 t (6H, CH3CH2O), 4.14 q (4H,
CH3CH2O), 4.66 d (1H, CHP, J 17.9 Hz), 6.41, 7.18 m (5H,
CHC6H5)
1.22 t (6H, CH3CH2O), 3.92 q (4H, CH3CH2O), 4.68 d(1H, CHP,
J 17.9 Hz), 6.55, 7.30 m (5H, CHC6H5), 7.07, 7.43 m (5H,
NHC6H5)
1.04 s [9H, C(CH3)3], 1.24 t (6H, CH3CH2O), 3.98 q (4H,
CH3CH2O), 4.68 d (1H, CHP, J 17.9 Hz), 6.99, 7.57 m (3H,
C4H3æ)
1.22 t (6H, CH3CH2O), 4.08 q (4H, CH3CH2O), 4.54 d (1H, CHP,
J 16.4 Hz), 7.16 m (5H, NHC6H5), 7.60, 8.40 m (4H, C5H4N)
0.94 s(3H, CH3), 1.04 c (3H, CH3CH2), 1.12 m (11H, C6H11-cyclo),
1.28 t (6H, CH3CH2O), 1.51 m (2H, CH3CH2), 4.14 q (4H,
CH3CH2O)
Ida
Ie
86 (8)
Ifa
Ig
78
77
121 122
22.60
28.52
Oily
substance
a
Constants of compounds Id and If are identical to published data [4, 5].
Table 3. Elemental analyses of compounds Ia c, Ie, Ig
Found, %
Compd.
Calculated, %
H
Formula
no.
C
H
P
C
P
Ia
Ib
Ic
Ie
Ig
57.31
54.10
62.70
53.93
57.70
10.31
10.89
8.58
8.92
10.00
10.62
11.83
9.57
10.56
10.52
C14H30NO3P
C12H28NO3P
C17H28NO3P
C13H24NO4P
C14H30NO3P
57.73
54.34
62.77
53.97
57.73
10.31
10.57
8.61
8.30
10.31
10.65
11.70
9.54
10.72
10.65
EXPERIMENTAL
sium carbonate and 5 mol% TBAI. The mixture was
stirred for 15 min at room temperature, then
0.025 mol (3.8 g, 4.5 ml) of N-cyclohexylbutyral-
imine was added. The reaction mixture was heated to
40 45 C for 5 h. Then to the solution was added
15 ml of water, and the mixture was stirred till
K2CO3 dissolved. The organic layer was separated,
the water layer was extracted with chloroform (3
5 ml). The solvent was distilled off, the residue was
distilled in a vacuum. Yield of compound Ia 5.8 g
(80%).
1H NMR spectra were recorded on spectrometer
Tesla BS-147 with TMS as external reference.
31P NMR spectra were registered on Varian FT-80
instrument with TMS as internal reference, 85%
H3PO4 as external reference.
Reaction between O,O-diethyl phosphite and
N-cyclohexylbutyralimine (Ia) (general procedure).
To 0.025 mol (3.5 g, 3.2 ml) of O,O-diethyl phos-
phite in 10 ml of anhydrous benzene was added
0.05 mol (6.9 g) of freshly calcined powder of potas-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 4 2002

486
KABACHNIK et al.
Reaction of O,O-diethyl phosphite with N-tert-
(20 g) of N-phenyl-3-pyridinecarboxaldimine. The
precipitate was filtered off, the compound obtained
was purified by recrystallization from hexane toluene
mixture (1: 1). Yield of compound If 27.6 g (78%).
butylbutyralimine (Ib). The reaction was carried out
as described above using 0.025 mol (3.5 g, 3.2 ml)
of O,O-diethyl phosphite and 0.025 mol (3.2 g,
3.9 ml) of N-tert-butylbutyralimine. Yield of com-
pound Ib 5.1 g (77%).
Reaction of O,O-diethyl phosphite with N-cyclo-
hexylbutylidene-2-imine (Ig). The reaction was
carried out as described above using 0.0125 mol
(1.85 g, 1.6 ml) of O,O-diethyl phosphite and
0.0125 mol (1.9 g) of N-cyclohexylbutylidene-2-
imine at room temperature for 18 h. To the solution
was added 10 ml of water, and the mixture was stir-
red till K2CO3 dissolved. The organic layer was
separated, the water layer was extracted with chloro-
form (3 5 ml). The solvent was distilled off, the
residue was treated with ether (3 10 ml). Yield of
compound Ig 2.8 g (77%).
Reaction of O,O-diethyl phosphite with N-cyclo-
hexylbenzalimine (Ic). The reaction was carried out
as described above using 0.012 mol (1.7 g, 1.6 ml) of
O,O-diethyl phosphite and 0.012 mol (2.3 g) of
N-cyclohexylbenzalimine. Yield of compound Ic
2.9 g (74%).
Reaction of O,O-diethyl phosphite with
N-phenylbenzalimine (Id). The reaction was carried
out as described above using 0.025 mol (3.5 g,
3.2 ml) of O,O-diethyl phosphite and 0.025 mol
(4.5 g) of N-phenylbenzalimine. Yield of compound
Id 6.3 g (79%).
REFERENCES
1. Texier-Boullet, F. and Foucaud, A., Tetrahedron Lett.,
1980, pp. 2161; Texier-Boullet, F. and Foucaud, A.,
Synthesis, 1982, p. 916.
2. Kossev, K., Troev, K., and Roundhill, D.M., Phos-
phorus, Sulfur, Silicon, 1993, vol. 81, p. 1.
3. Changtao, Q. and Taisheng, H., J. Org. Chem., 1998,
vol. 63, p. 4125.
Reaction of O,O-diethyl phosphite with N-tert-
butylfurfuralimine (Ie). The reaction was carried out
as described above using 0.025 mol (3.5 g, 3.2 ml) of
O,O-diethyl phosphite and 0.025 mol (4.5 g) of N-tert-
butylfurfuralimine. Yield of compound Ie 3.7 g
(76%).
4. Pudovik, A.N., Dokl. Akad Nauk SSSR, 1952, vol. 83,
pp. 865 868.
5. Boduszek, B., Tetrahedron, 1996, vol. 52,
pp. 12483 12494.
Reaction of O,O-diethyl phosphite with
N-phenyl-3-pyridinecarboxaldimine (If). Likewise
was performed a reaction of 0.11 mol (15.2 g,
14.2 ml) of O,O-diethyl phosphite and 0.11 mol
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 4 2002