Phosphorylation of Amino(aryl)methylphosphonates by the Atherton-Todd Reaction

Full text of DOI:10.1134/S1070428010100246

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 10, pp. 1579–1580. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © L.I. Minaeva, L.S. Patrikeeva, M.M. Kabachnik, I.P. Beletskaya, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46,
No. 10, pp. 1572–1573.
SHORT
COMMUNICATIONS
Phosphorylation of Amino(aryl)methylphosphonates
by the Atherton–Todd Reaction
L. I. Minaeva, L. S. Patrikeeva, M. M. Kabachnik, and I. P. Beletskaya
Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
e-mail: mariamk@mail.ru
Received May 27, 2010
DOI: 10.1134/S1070428010100246
1
Among amidophosphate derivatives, promising are
N-(α-phosphoryl)amidophosphates possessing two
four-coordinate phosphorus atoms. These organophos-
phorus compounds exhibit biological activity and are
used as chelating ligands for complex formation with
some metal ions [1, 2]. They are usually synthesized
by phosphorylation of amino phosphonates with di-
ethyl chlorophosphate [3].
The product structure was confirmed by their H,
1
3
31
C, and P NMR spectra and elemental analyses.
Compounds IIa–IIe displayed in the P NMR spectra
doublet signals at δ 6.2–6.8 and 22.2–22.6 ppm with
coupling constants of 40.2–42.7 Hz. In the H NMR
spectra of IIa–IIe, the NCH proton characteristically
resonated at δ 4.4–4.6 ppm, and the corresponding
3
1
P
1
1
3
carbon signal appeared in the C NMR spectra as
a doublet at δ 51.3–53.8 ppm (J = 153–156 Hz).
C
PC
We were the first to perform phosphorylation of
amino(aryl)methylphosphonates having a primary
amino group under the Atherton–Todd reaction condi-
tions. The reactions of amino(aryl)methylphosphonates
Ia–Ie with diethyl phosphonate and carbon tetra-
chloride in the presence of triethylamine were carried
out at room temperature, on heating at 110ºC, and
under microwave irradiation. The reactions under
microwave irradiation were complete in 30–40 min,
and the corresponding N-(α-phosphoryl)amidophos-
phates IIa–IIe were obtained in 63–93% yield. No
reaction occurred at room temperature, whereas after
heating for 24 h at 110°C compounds IIa–IIe were
isolated in poor yields (15–20%) due to predominant
formation of pyrophosphate on prolonged heating.
Diethyl aryl(diethoxyphosphorylamino)methyl-
phosphonates IIa–IIe (general procedure). Carbon
tetrachloride, 20 mmol (3.08 g, 2.11 ml), triethylamine,
1
5 mmol (1.52 g, 1.08 ml), and aminophosphonate
Ia–Ie, 10 mmol, were added in succession to 10 mmol
(1.38 g, 1.29 ml) of diethyl phosphonate. The reaction
was carried out in an open vessel under microwave
irradiation (102 W, 115°C). The precipitate of triethyl-
amine hydrochloride was filtered through a glass filter,
the filtrate was cooled and evaporated on a rotary
evaporator, and the residue was subjected to column
chromatography on silica gel using chloroform–metha-
nol (50:1) as eluent.
Diethyl α-[(diethoxyphosphoryl)amino]benzyl-
phosphonate (IIa). Reaction time 40 min. Yield 3.22 g
NH2
31
(
85%), oily substance. P NMR spectrum (CDCl ), δ ,
3
P
+
HP(O)(OEt)2
3
ppm: 6.78 d and 22.20 d ( J = 41.3 Hz) [3].
PP
R
P(O)(OEt)2
Diethyl α-[(diethoxyphosphoryl)amino]-4-meth-
ylbenzylphosphonate (IIb). Reaction time 35 min.
Ia–Ie
CCl , Et N, MW
P(O)(OEt)
2
4
3
1
HN
Yield 3.46 g (88%), oily substance. H NMR spectrum
3
0–40 min
3
(
7
1
CDCl ), δ, ppm: 1.06 t (3H, CH CH OPNH, J =
3
3
2
3
–
CHCl , –Et N·HCl
3
3
R
P(O)(OEt)2
.2 Hz), 1.12 t (3H, CH CH OPNH, J = 7.2 Hz),
.27 t (3H, CH CH OPCH, J = 6.8 Hz), 1.33 t (3H,
CH CH OPCH, J = 6.8 Hz), 1.88 br.s (1H, NH),
3 2
3
IIa–IIe
3
2
3
R = Ph (a), 4-MeC
6
H
4
(b), 4-MeOC
6
H
4
(c),
3
2
4
-Me NC (d), 3-O
2
6
H
4
2
NC (e).
6
H
4
2.19 s (3H, CH C H ), 3.65–3.70 m (2H, NHPOCH ),
3 6 4 2
1
579

1
3
580
MINAEVA et al.
.90–3.95 m (2H, NHPOCH ), 3.97–4.02 m (2H,
CHPOCH ), 4.12–4.17 m (2H, CHPOCH ), 4.47 d.t
(CH CH OPCH), 40.51 s (CH N), 52.28 d (PCH,
JCP = 153.8 Hz), 63.05 s and 63.09 s (CH OPNH),
2
3
2
3
1
2
2
2
2
3
(
(
(
1H, PCH, J = 23.1, J = 12.1 Hz), 7.15 d and 7.28 d
63.33 s and 63.37 s (CH OPCH); 127.85 s, 128.45 s,
2
3
13
p
31
2H each, C H , J = 8.4 Hz). C NMR spectrum
136.73 s (C H ); 153.53 s (C ). P NMR spectrum
6
4
6 4
3
CDCl ), δ , ppm: 15.72 s and 16.02 s (CH CH O-
(CDCl ), δ , ppm: 6.68 d and 22.20 d ( J = 40.2 Hz).
3 P PP
3
C
3
2
PNH), 16.12 s and 16.42 s (CH CH OPCH), 21.14 s
Found, %: C 48.51; H 7.81; N 6.82. C H N O P .
Calculated, %: C 48.34; H 7.64; N 6.63.
3
2
17 32 2 6 2
1
(
CH C H ), 51.94 d (PCH, J = 154.3 Hz), 63.09 s
3
6
4
CP
and 63.13 s (CH OPNH), 63.37 s and 63.41 s
2
Diethyl α-[(diethoxyphosphoryl)amino]-3-nitro-
(
(
CH OPCH); 127.68 s, 129.17 s, 133.45 s, 137.91 s
2
benzylphosphonate (IIe). Reaction time 30 min. Yield
3
1
C H ). P NMR spectrum (CDCl ), δ , ppm: 6.70 d
1
6
4
3
P
3
(
7
1
.48 g (82%), oily substance. H NMR spectrum
3
and 22.27 d ( J = 42.7 Hz). Found, %: C 49.02;
3
PP
CDCl ), δ, ppm: 1.04 t (3H, CH CH OPNH, J =
3 3 2
H 7.51; N 4.14. C H NO P . Calculated, %: C 48.85;
3
1
6
29
6 2
.2 Hz), 1.11 t (3H, CH CH OPNH, J = 7.2 Hz),
3 2
.25 t (3H, CH CH OPCH, J = 7.2 Hz), 1.32 t (3H,
CH CH OPCH, J = 7.2 Hz), 2.52 br.s (1H, NH),
H 7.43; N 3.56.
3
3
2
3
Diethyl α-[(diethoxyphosphoryl)amino]-4-me-
thoxybenzylphosphonate (IIc). Reaction time 35 min.
3 2
3.60–3.65 m (2H, NHPOCH ), 3.95–4.00 m (2H,
2
1
Yield 3.80 g (93%), oily substance. H NMR spectrum
CHPOCH ), 4.01–4.05 m (2H, CHPOCH ), 4.12–
2
2
3
2
(
6
1
CDCl ), δ, ppm: 1.06 t (3H, CH CH OPNH, J =
4.17 m (2H, NHPOCH ), 4.62 d.t (1H, PCH, J = 22.7,
3
3
2
3
2
3
.7 Hz), 1.11 t (3H, CH CH OPNH, J = 6.7 Hz),
.24 t (3H, CH CH OPCH, J = 6.7 Hz), 1.31 t (3H,
CH CH OPCH, J = 6.7 Hz), 2.20 br.s (1H, NH),
J = 10.5 Hz); 7.55 d, 7.69 t, 7.84 d, 8.17 d (4H, C H ).
3
2
6
4
3
13
3
2
C NMR spectrum (CDCl ), δ , ppm: 15.85 s and
3 C
3
3
2
15.93 s (CH CH OPNH), 16.33 s and 16.41 s
3 2
1
3
.79 s (3H, CH OC H ), 3.64–3.69 m (2H, NHPO-
(CH CH OPCH), 53.81 d (PCH, J = 154.6 Hz),
3
6
4
3 2 CP
CH ), 3.93–3.97 m (2H, NHPOCH ), 3.98–4.03 m
62.45 s and 62.49 s (CH OPNH), 63.12 s and 63.16 s
2
2
2
(
4
7
2H, CHPOCH ), 4.12–4.17 m (2H, CHPOCH ),
(CH OPCH); 126.21 s, 127.01 s, 133.15 s, 133.95 s,
2
2
2
2
3
p
31
.44 d.t (1H, PCH, J = 22.8, J = 10.8 Hz), 6.85 d and
142.03 s (C H ); 149.87 s (C ). P NMR spectrum
6 4
3
13
3
.31 d (2H each, C H , J = 8.3 Hz). C NMR spec-
(CDCl ), δ , ppm: 6.28 d and 20.56 d ( J = 41.4 Hz).
3 P PP
6
4
trum (CDCl ), δ , ppm: 15.76 s and 16.02 s (CH CH -
Found, %: C 42.46; H 6.18; N 6.60. C H N O P .
3
C
3
2
15 26 2 8 2
OPNH), 16.17 s and 16.37 s (CH CH OPCH), 51.56 d
Calculated, %: C 41.98; H 6.01; N 6.61.
3
2
1
(
PCH, J = 156.3 Hz), 55.25 s (CH OC H ), 62.94 s
1
13
31
CP
3
6
4
The H, C, and P NMR spectra were recorded
and 62.98 s (CH OPNH), 63.24 s and 63.28 s
2
from solutions in CDCl on a Bruker Avance-400 spec-
3
(
CH OPCH); 113.83 s, 115.95 s, 129.00 s, 159.39 s
2
trometer at 400, 100.6, and 161.9 MHz, respectively,
using the solvent signals as reference (δ 7.28 ppm,
δC 77.10 ppm). The progress of reactions and the
purity of products were monitored by TLC on Silufol
UV-254 plates using chloroform–methanol (50:1) as
eluent. Preparative column chromatography was per-
formed on silica gel (40–60 μm, Merck).
3
1
(
C H ). P NMR spectrum (CDCl ), δ , ppm: 6.78 d
6
4
3
P
3
and 22.43 d ( J = 40.6 Hz). Found, %: C 47.04;
PP
H 7.30; N 3.65. C H NO P . Calculated, %: C 46.95;
1
6
29
7 2
H 7.14; N 3.42.
Diethyl α-[(diethoxyphosphoryl)amino]-4-di-
methylaminobenzylphosphonate (IId). Reaction
time 40 min. Yield 2.66 g (63%), oily substance.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 08-03-00178).
1
H NMR spectrum (CDCl ), δ, ppm: 1.03 t (3H,
3
3
CH CH OPNH, J = 7.2 Hz), 1.10 t (3H, CH CH O-
PNH, J = 7.2 Hz), 1.26 t (3H, CH CH OPSH, J =
3
2
3
2
3
3
3
2
3
7
2
.2 Hz), 1.33 t (3H, CH CH OPCH, J = 7.2 Hz),
3 2
REFERENCES
.08 br.s (1H, NH), 2.94 s (6H, CH N), 3.63–3.68 m
3
(
3
2H, NHPOCH ), 3.92–3.97 m (2H, NHPOCH ),
2
2
1. Skropeta, D., Schwörer, R., and Schmidt, R.R., Bioorg.
Med. Chem. Lett., 2003, vol. 13, p. 3351.
2. Cui, Z., Zhang, J., Wang, F., Wang, Y., Miao, Z., and
Chen, R., Carbohydr. Res., 2008, vol. 343, p. 2530.
3. Hammerschmidt, F. and Hanbauer, M., J. Org. Chem.,
.97–4.02 m (2H, CHPOCH ), 4.12–4.16 m (2H,
2
2
3
CHPOCH ), 4.51 d.t (1H, PCH, J = 22.5, J =
1
6
2
3
0.3 Hz), 7.33 d and 7.41 d (2H each, C H , J =
.3 Hz). C NMR spectrum (CDCl ), δ , ppm: 15.70 s
6
4
1
3
3
C
and 15.78 s (CH CH OPNH), 16.37 s and 16.43 s
2000, vol. 65, p. 6121.
3
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 10 2010