Direct phosphorylation in the synthesis of new bis(phosphorylamino)pyridine ligands

Article abstract of DOI:10.1016/j.mencom.2010.06.014

A simple and efficient synthetic approach to new oligodentate ligands, 2,6-bis(phosphorylamino)pyridine and related compounds, is based on the reaction of diphenylphosphinic chloride Ph₂POCl with various diamines.

Full text of DOI:10.1016/j.mencom.2010.06.014

Mendeleev
Communications
Mendeleev Commun., 2010, 20, 223–225
Direct phosphorylation in the synthesis of new
bis(phosphorylamino)pyridine ligands
Pavel S. Lemport, Petr N. Ostapchuk, Anastasiya A. Bobrikova,* Pavel V. Petrovskii,
Nikolai D. Kagramanov, Georgy V. Bodrin and Edward E. Nifant’ev
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 495 135 6549; e-mail: nastenka-bobrik@yandex.ru
DOI: 10.1016/j.mencom.2010.06.014
A simple and efficient synthetic approach to new oligodentate ligands, 2,6-bis(phosphorylamino)pyridine and related compounds,
is based on the reaction of diphenylphosphinic chloride Ph2POCl with various diamines.
Neutral organophosphorus complexing agents and extractants
are characterized by higher selectivity in comparison with their
organic (carbonyl) analogues.1 Moreover, the introduction of
additional phosphoryl groups in many cases makes it possible
to increase considerably (sometimes by dozens of times) the
efficiency of extraction of rare-earth metals from liquid radio-
active wastes.2
H2N
N
NH2
1a
It is well known that poly(diphenylphosphoryl)alkanes and
poly(diphenylphosphorylmethyl)arenes are used for extraction
of tetra- and hexavalent actinides and lanthanides;1 at the same
time, trivalent transition metals are extracted with them much
poorer. However, polydentate nitrogen heterocycles – tripyridyl-
triazines, terpyridines, bis(benzimidazolyl)pyridines, bis(benzo-
thiazolyl)pyridines and, especially, polyalkyl-substituted 2,6-bis-
(1,2,4-triazin-3-yl)pyridines – are much more efficient ligands
for concentrating trivalent radionuclides.3,4
H2N
N
N
NH2
H2N
N
N
H
N
NH2
3d
2a
HN
N
NH
Ph2P
PPh2
O
O
1b
The design of ligand systems containing phosphoryl groups
alongside pyridine fragments opens new prospects for the
efficient and selective extraction of trivalent lanthanides and
actinides. Moreover, interesting luminescent properties of hybrid
compounds containing phosphorus and nitrogen (including
phosphorus-containing pyridines and naphthyridines) and their
complexes with various metals were recently documented.5–8
Interesting results concerned the synthesis and coordination
properties of thiophosphoryl pyridine-type ligands were also
obtained.9
In this context, we previously reported a highly efficient and
regioselective synthesis of 2-phosphorylalkyl- and 2-phosphoryl-
amino-substituted naphthyridines.10–12 These compounds differ
from each other mainly in the structure and the nature of linkers
between phosphoryl groups and heteroaromatic fragments. They
behave as oligodentate ligands toward lanthanide cations13 and
can be used as selective extractants upon partitioning of radio-
nuclides.14
HN
N
N
NH
HN
Ph2P
N
N
H
N
NH
Ph2P
PPh2
PPh2
O
O
O
O
3e
2b
Scheme 1
different sizes of ligand contours. Diphenylphosphinic chloride
Ph2POCl was used as a phosphorylating agent in all cases
(Scheme 1).
Initially, we studied a reaction of Ph2POCl with com-
mercially available diamine 1a. The stirring of a suspension
of the reactants in refluxing chloroform in the presence of
triethylamine was a more convenient synthetic procedure than
the reaction in benzene15 or pyridine.14 The first advantage
of this procedure is a possibility to monitor reaction course via
the dissolution of the starting diamine, and the second one is the
simple procedure of isolation of the target bis(phosphoryl-
amino)pyridine. The reaction was complete in 5 h, and product
1b was isolated in 80% yield.
The bisphosphorylation of diamine 2a, which can be obtained
from 1a in one stage,16 has been carried out under the same
conditions. The reaction was complete in a longer time (18 h)
and product 2b was isolated in 76% yield.
The preparation of ligand 3e is possible on the basis of
2,7-diamino-1,8-naphthyridine 3d. The synthesis of this diamine
demands a longer chain of transformations.17,18 Therefore,
the first aim was to obtain a sufficient amount of diamine 3d
(Scheme 2).
The aim of this study was to develop a facile procedure for
the synthesis of bis(phosphorylamino)-substituted molecular
architectures that differ in the structure of pyridine-containing
bridge between two phosphoryl groups. One can expect that the
compounds of this type will be capable to function as multidentate
ligands and to form complexes with one or more metal centres.
The direct phosphorylation of amino-substituted pyridines
(and related compounds) with chlorides of pentavalent phos-
phorus acids provides a convenient synthetic route to such
systems.10 We used commercially available 2,6-diaminopyridine
1a and heterocyclic diamines 2a and 3d obtained on its basis
as starting materials for constructing target compounds with
We improved certain stages leading to 2,7-diamino-1,8-
naphthyridine 3d. In particular, we developed a facile one-pot
process for preparing 2,7-dihydroxy-1,8-naphthyridine 3b in an
– 223 –
© 2010 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2010, 20, 223–225
H2N
N
NH2
H2N
N
N
OH
N
N
X
P
HN
P
N
N
NH
P
Ph
Ph
Ph
Ph
Ph
Ph
1a
3a
Lnz+
Lnz+
O
O
O
X = NH, CMe2, CH2CH2
Ln = Nd, Eu, Lu
3d
HO
N
N
OH
Cl
N
N
Cl
3b
3c
Figure 1 Schematic structures of lanthanide complexes with phosphoryl-
substituted naphthyridines.
Scheme 2
almost quantitative yield over two initial stages. This process is
less time consuming and labour intensive and provides the saving
of reagents. The formation of bis(phosphorylamino)-substituted
compound 3e required phosphorylation for 24 h at reflux.
Bisphosphorylation product 3e was obtained in 76% yield.
The bis(phosphorylamino)-substituted ligands obtained in this
work are white solids with high melting points. The 31P NMR
spectra of the bisphosphorylated diamines show singlets with
chemical shifts d 15–20 ppm typical of the phosphorus atom in
the corresponding environment. The 1H NMR spectra† of all the
compounds exhibit expected chemical shifts and multiplicity.
The mass spectra of compounds 1b, 2b and 3e display the intense
peaks of molecular ions; moreover, peaks related to the main
fragmentation directions of these molecules are identified.
Previously we have shown that 2-monophosphoryl-substituted
1,8-naphthyridines reveal highest possible denticity in complexa-
tion with lanthanide nitrates. In this case, both nitrogen atoms of
pyridine rings and the oxygen atom of the phosphoryl group take
part in the formation of coordinative linkages (Figure 1).13,19,20
In this work we have obtained a series of new hybrid mole-
cules containing phosphorus and heterocyclic nitrogen that incor-
porate ligand cavities of various size and type. One can expect
the maximal denticity of compounds 1b, 2b and 3e in complexes
with relative metals (Figure 1). Investigations of complexation
abilities of newly synthesized ligands are in progress now.
References
1 M. I. Kabachnik and Yu. M. Polikarpov, Zh. Obshch. Khim., 1988, 58,
1937 (in Russian).
2 O. I. Artyushin, E. V. Sharova, I. L. Odinets, K. A. Lyssenko, D. G.
Golovanov, T. A. Mastryukova, G. A. Pribylova, I. G. Tananaev and
G. V. Myasoedova, Izv. Akad. Nauk, Ser. Khim., 2006, 1386 (Russ.
Chem. Bull., Int. Ed., 2006, 55, 1440).
3 Z. Kolarik, U. Mullich and F. Gassner, Solvent Extr. Ion Exch., 1999,
17, 23.
4 C. Musikas, Inorg. Chim. Acta, 1987, 140, 197.
Bis[6-(diphenylphosphorylamino)pyridin-2-yl]amine 2b. To a suspen-
sion of diamine 2a (603 mg, 3 mmol) in CHCl3 (20 ml), Ph2POCl (1.42 g,
1.2 ml, 6 mmol) was added with stirring at 20 °C, and then Et3N (0.7 g,
0.97 ml, 6.9 mmol) was added dropwise. The resulting mixture was refluxed
for 18 h. After that, the mixture was washed with water (2×10 ml), and com-
bined water layers were washed with CHCl3 (10 ml). Combined organic
layers was filtered through Al2O3, dried over MgSO4, and then CHCl3
was distilled off under reduced pressure, giving 1.37 g (76%) of yellowish
solid, which was washed with hexane. After recrystallization from CHCl3,
0.94 g (52%) of 2b as a white powder was isolated. Mp 179–180 °C.
31P NMR, d: 15.0. 1H NMR, d: 8.57 (d, 2H, NHP, JHP 11.1 Hz), 8.46 (s,
1H, Py–NH–Py), 7.80–7.86 (m, 8H, o-Ph), 7.48–7.53 (m, 12H, m-Ph,
p-Ph), 7.27 (t, 2H, Py-H4, JHH 7.8 Hz), 7.00 (d, 2H, Py-H3, JHH 8.1 Hz),
6.43 (d, 2H, Py-H5, JHH 7.5 Hz). MS, m/z: 601 [M]+ (42.1), 600 [M – H]+
(11.4), 524 [M – Ph]+ (5.5), 400 [C22H19N5OP]+ (39.5), 385 [C22H18N4OP]+
(8.9), 217 [C12H11NOP]+ (100), 201 [C12H10PO]+ (97.1), 77 [Ph]+
(15.6). Found (%): C, 67.75; H, 4.90; N, 11.70; P, 10.41. Calc. for
C34H29N5O2P2 (%): C, 67.88; H, 4.86; N, 11.64; P, 10.30.
2,7-Dihydroxy-1,8-naphthyridine 3b. To a conc. H2SO4 (40 ml), diamine
1a (4.4 g, 40 mmol) was added with stirring and cooling in an ice bath
(0–5 °C). To the resulting solution carefully grounded DL-malic acid
(6.0 g, 44 mmol) was added in small portions. Then, the resulted
solution was heated to 110 °C until stopping of gassing. After that, the
reaction mixture was kept at this temperature for additional 30 min
(2–2.5 h total). Then, NaNO2 (3.3 g, 48 mmol) was carefully added to
the resulting mixture with stirring and cooling in an ice bath (0–5 °C).
Mixture was stirred for 10 min at 20 °C, poured over crushed ice and
allowed to stand for 15 min. The solution was neutralized by Na2CO3,
acidified by acetic acid (pH 3.5), the resulting precipitate was filtered off
and carefully washed with cold water to give 6.35 g (98%) of naphthyri-
dine 3b as a light-brown powder. Mp 322–323 °C (lit.,17 321–323 °C).
2,7-Bis(diphenylphosphorylamino)-1,8-naphthyridine 3e. To a suspen-
sion of diamine 3d (480 mg, 3 mmol) in CHCl3 (20 ml), Ph2POCl (1.42 g,
1.2 ml, 6 mmol) was added with stirring at 20 °C, and then Et3N (0.7 g,
0.97 ml, 6.9 mmol) was added dropwise. The resulting mixture was refluxed
for 24 h. After that, the mixture was worked up as it described for 2b.
Yield, 1.28 g (76%) of 3e, white powder, mp 321–322 °C (from EtOH,
decomp.). 31P NMR, d: 20.4. 1H-{31P} NMR, d: 7.87 (d, 8H, o-Ph,
JHH 7.0 Hz), 7.55 (d, 2H, Napy-H4, Napy-H5, JHH 8.6 Hz), 7.48 (t, 4H,
p-Ph, JHH 7.3 Hz), 7.41 (t, 8H, o-Ph, JHH 7.1 Hz), 6.97 (d, 2H, Napy-H3,
Napy-H3, JHH 8.6 Hz). MS, m/z: 560 [M]+ (49.7), 559 [M – H]+ (38.9),
483 [M – Ph]+ (14.6), 359 [C20H16N4OP]+ (44.3), 343 [C20H15N3OP]+
(39.8), 219 [C12H11NOP]+ (100), 201 [C12H10PO]+ (68.4), 77 [Ph]+
(13.9). Found (%): C, 68.51; H, 4.69; N, 9.91; P, 10.73. Calc. for
C32H26N4O2P2 (%): C, 68.57; H, 4.68; N, 10.00; P, 11.05.
†
The NMR spectra were recorded on a Bruker Avance-400 spectrometer
operating at 400.13 (1H) and 161.98 MHz (31P) in [2H6]DMSO or CDCl3
(for 3e) solutions using the residual proton signals of the solvent as an
internal reference (1H) and 85% H3PO4 (31P) as external reference. The
mass spectra were measured on a Finnigan Polaris Q mass spectrometer.
2,6-Diaminopyridine (Acros Organics) was recrystallized from CHCl3
(white plates). Diphenylphosphinylchloride Ph2POCl (Aldrich) was
purified by vacuum distillation. Reactions with Ph2POCl were carried
out in an argon atmosphere. Compounds 3c17 and 3d18 were synthesized
by previously described procedures. Solvents used for syntheses were
purified and dried by known procedures.21
2,6-Bis(diphenylphosphorylamino)pyridine 1b. To a suspension of
2,6-diaminopyridine (1.09 g, 10 mmol) in CHCl3 (30 ml), Ph2POCl (4.97 g,
4 ml, 21 mmol) was added with stirring at 20 °C, and then Et3N (2.33 g,
3.2 ml, 23 mmol) was added dropwise. The resulting mixture was refluxed
for 5 h. After that, the mixture was allowed to cool to 20 °C. White
precipitate was filtered off, washed carefully with cold water and dried
over CaCl2 in a vacuum. By this procedure 4.07 g (80%) of 1b was
isolated as a white powder, mp 285–286 °C (from CHCl3, decomp.).
31P NMR, d: 15.9. 1H NMR, d: 8.33 (d, 2H, NHP, JHP 11.0 Hz), 7.67–7.74
(m, 8H, o-Ph), 7.47–7.56 (m, 12H, m-Ph, p-Ph), 7.22 (t, 1H, Py-H4,
JHH 8.0 Hz), 6.38 (d, 2H, Py-H3, Py-H5, JHH 8.0 Hz). MS, m/z: 509 [M]+
(94.9), 508 [M – H]+ (34.1), 432 [M – Ph]+ (22.9), 309 [C17H15N3OP]+
(50.2), 292 [C17H14N2OP]+ (35.3), 216 [C12H11NOP]+ (7.3), 201
[C12H10PO]+ (43.3), 185 [C12H10P]+ (100), 77 [Ph]+ (11.8). Found (%):
C, 68.40; H, 4.90; N, 8.31; P, 12.08. Calc. for C29H25N3O2P2 (%): C, 68.37;
H, 4.95; N, 8.25; P, 12.16.
Bis(6-aminopyridin-2-yl)amine 2a. This compound was synthesized
as described elsewhere.15 Yield, 41% (no indicated yield value in ref. 16).
Mp 177–178 °C. 1H NMR, d: 8.52 (s, 1H, Py–NH–Py), 7.20 (t, 2H,
Py-H4, JHH 7.8 Hz), 6.89 (d, 2H, Py-H3, JHH 7.8 Hz), 5.91 (d, 2H, Py-H5,
JHH 7.8 Hz), 5.57 (s, 4H, NH2). Found (%): C, 59.60; H, 5.49; N, 34.86.
Calc. for C10H11N5 (%): C, 59.69; H, 5.51; N, 34.80.
– 224 –

Mendeleev Commun., 2010, 20, 223–225
5
6
7
8
9
K. Nakatani, S. Horie, T. Murase, S. Hagihara and I. Saito, Bioorg.
Med. Chem., 2003, 11, 2347.
15 D. V. Tolkachev, A. A. Khodak, S. P. Solodovnikov, N. N. Bubnov and
M. I. Kabachnik, Izv. Akad. Nauk SSSR, Ser. Khim., 1990, 2756 (Bull.
Acad. Sci. USSR, Div. Chem. Sci., 1990, 39, 2498).
A. Fernández-Mato, G. Blanco, J. M. Quintela and C. Peinador, Tetrahedron
,
2008, 64, 3446.
16 J. Bernstein, B. Stearns, E. Shaw and W. A. Lott, J. Am. Chem. Soc.,
J.-F. Zhang, W.-F. Fu, X. Gan and J. H. Chen, Dalton Trans., 2008,
3093.
1947, 69, 1151.
17 G. R. Newkome, S. J. Gabris, V. K. Majestic, F. R. Fronczek and G. Chiari,
J. Org. Chem., 1981, 46, 834.
18 P. S. Corbin, S. C. Zimmerman, P. A. Thiessen, N. A. Hawryluc and
X. Li, H. Song, K. Nakatani and H.-B. Kraatz, Anal. Chem., 2007, 79,
2552.
A. S. Batsanov, A. V. Churakov, M. A. M. Easson, L. J. Govenlock,
J. A. K. Howard, J. M. Moloney and D. Parker, J. Chem. Soc., Dalton
Trans., 1999, 323.
T. J. Murray, J. Am. Chem. Soc., 2001, 123, 10475.
19 A. G. Matveeva, P. S. Lemport, M. P. Passechnik, R. R. Aysin, L. A.
Leites and E. E. Nifant’ev, Izv. Akad. Nauk, Ser. Khim., 2009, 1375
(Russ. Chem. Bull., Int. Ed., 2009, 58, 1416).
20 A. G. Matveeva, P. S. Lemport, A. V. Vologzhanina, S. V. Matveev
and E. E. Nifant’ev, in XXIV International Chugaev Conference on
Coordination Chemistry, Book of Abstracts, St. Petersburg, Russia,
June 15–19, 2009, p. 320.
21 A. Weissberger, E. S. Proskauer, J. A. Riddik and E. E. Toops, Organic
Solvents. Physical Properties and Methods of Purifications, Interscience,
New York, 1955.
10 P. S. Lemport, E. I. Goryunov, A. V. Vologzhanina, N. D. Kagramanov,
I. B. Goryunova and E. E. Nifant’ev, Izv. Akad. Nauk, Ser. Khim., 2009,
1404 (Russ. Chem. Bull., Int. Ed., 2009, 58, 1445).
11 P. S. Lemport, G. V. Bodrin, M. P. Pasechnik, A. G. Matveeva, P. V.
Petrovskii, A. V. Vologzhanina and E. E. Nifant’ev, Izv. Akad. Nauk,
Ser. Khim., 2007, 1846 (Russ. Chem. Bull., Int. Ed., 2007, 56, 1911).
12 P. S. Lemport, G. V. Bodrin, A. I. Belyakov, P. V. Petrovskii, A. V.
Vologzhanina and E. E. Nifant’ev, Mendeleev Commun., 2009, 19, 303.
13 A. G. Matveeva, P. S. Lemport, L. A. Leites, R. R. Aysin, A. V.
Vologzhanina, Z. A. Starikova, M. P. Passechnik and E. E. Nifant’ev,
Inorg. Chim. Acta, 2009, 362, 3187.
14 P. S. Lemport, E. I. Goryunov, I. B. Goryunova, A. A. Letyushov, A. M.
Safiulina, I. G. Tananaev, E. E. Nifant’ev and B. F. Myasoedov, Dokl.
Akad. Nauk, 2009, 425, 773 [Dokl. Chem. (Engl. Transl.), 2009, 425, 84].
Received: 1st March 2010; Com. 10/3478
– 225 –