2-(N-Phosphorylamino)-substituted 1, 8-naphthyridines. Synthesis and structure

Article abstract of DOI:10.1007/s11172-009-0194-0

The previously unknown 2-(N-phosphorylamino)-substituted 1, 8-naphthyridines were synthesized by the direct phosphorylation of 2-amino-5, 7-dimethyl-1, 8-naphthyridine with phosphoryl chlorides of different structures. The structures of the reaction produ

Full text of DOI:10.1007/s11172-009-0194-0

Russian Chemical Bulletin, International Edition, Vol. 58, No. 7, pp. 1445—1451, July, 2009
1445
2ꢀ(NꢀPhosphorylamino)ꢀsubstituted 1,8ꢀnaphthyridines.
Synthesis and structure
P. S. Lemport, E. I. Goryunov, A. V. Vologzhanina, N. D. Kagramanov, I. B. Goryunova, and E. E. Nifant´ev
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: phoc@ineos.ac.ru
The previously unknown 2ꢀ(Nꢀphosphorylamino)ꢀsubstituted 1,8ꢀnaphthyridines were synꢀ
thesized by the direct phosphorylation of 2ꢀaminoꢀ5,7ꢀdimethylꢀ1,8ꢀnaphthyridine with phosꢀ
phoryl chlorides of different structures. The structures of the reaction products were confirmed
1
by mass spectrometry, H and 31P NMR spectroscopy, and Xꢀray diffraction study (for one of
the compounds).
Key words: phosphorylation, 1,8ꢀnaphthyridines, phosphoryl chlorides, synthesis, strucꢀ
ture, mass spectra, NMR spectra, Xꢀray diffraction study.
The search for new original ligands, that can selectively
form stable complexes with metals belonging to different
Groups of the Periodic table, is an interesting and imporꢀ
tant problem of modern chemistry. Investigations in this
area are associated with the necessity of solving problems
related to the purification and separation of nuclear waste
in industry, as well as the problems of metalꢀcomplex caꢀ
talysis and the creation of materials for the design of enerꢀ
gyꢀsaving equipment. In this context, coordination comꢀ
pounds containing ligand groups of several types1 have
attracted growing attention and have found increasing apꢀ
plication. Polynitrogenꢀcontaining heterocyclic ligands
have attracted great interest. Complexes of these ligands
with f elements, for example, with lanthanides, often disꢀ
play interesting photophysical (in particular, luminesꢀ
cence) properties and, hence, they can serve as materials
for the design of electroluminescent diodes.2 Along with
pyridines, triazoles, triazines, and phenanthrolines, parꢀ
ticular attention is given to 1,8ꢀnaphthyridines3,4 in which
the endocyclic nitrogen atoms are in the favorable arꢀ
rangement for the formation of chelate complexes with
different metal cations, including actinides and lanꢀ
thanides. The introduction of additional groups capable of
forming coordination bonds at positions 2 and 7 of the
heterocyclic moiety of 1,8ꢀnaphthyridine results in the
formation of oligodentate polyfunctional ligands, which
can form complexes of different types with metal salts.
The presence of PIIIꢀcontaining fragments in the side chains
of these ligands gives rise to an additional coordination
center and, correspondingly, to new coordination properꢀ
ties of 1,8ꢀnaphthyridine derivatives.1
phoryl fragment is bound to the heterocyclic moiety by
structurally different alkylene linkers of different lengths.
The coordination properties of these systems have been
studied, and these systems have shown to act as tridentate
ligands in complexes with lanthanides, both the nitroꢀ
gen atoms of the heterocyclic moiety and the oxygen atom
of the phosphoryl group being involved in coordinaꢀ
tion bonds.7
These data have stimulated the continuation of the
search for and design of tridentate organophosphorus
ligands based on 1,8ꢀnaphthyridine. It would be expected
that the best conditions for the complexation would be
achieved with the use of the —NH— bridge as a linker that
connects the ligand fragments (the heterocycle and the
phosphoryl group). In the presence of this bridge, not only
the distances between the endocyclic nitrogen atoms and
the phosphorus atom are optimized but also the electron
system of the chelating center is delocalized.
It is also known that 2ꢀaminoꢀ1,8ꢀnaphthyridine deꢀ
rivatives have a strong ability to form hydrogen bonds,8—10
due to which these compounds can be used as modern
tools for biochemical studies.11—14
The aim of the present study was to develop a conveꢀ
nient and efficient method for the synthesis of 2ꢀ(phosꢀ
phorylamino)ꢀsubstituted derivatives of 1,8ꢀnaphthyridine.
Results and Discussion
The aboveꢀmentioned compounds were successfully
synthesized by the direct phosphorylation of 2ꢀaminoꢀ1,8ꢀ
naphthyridines with phosphoryl chlorides (Scheme 1).
We chose 2ꢀaminoꢀ5,7ꢀdimethylꢀ1,8ꢀnaphthyridine
(1), which can easily be synthesized from cheap and comꢀ
Previously,5,6 we have synthesized a series of phosphoꢀ
alkyl derivatives of 1,8ꢀnaphthyridine, in which the phosꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1404—1409, July, 2009.
1066ꢀ5285/09/5807ꢀ1445 © 2009 Springer Science+Business Media, Inc.

1446
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
Lemport et al.
Scheme 1
Taking into account that the starting heterocyclic
amine 1 is poorly soluble in most of organic solvents,
2ꢀphosphorylaminoꢀ1,8ꢀnaphthyridines (3) were initially
synthesized by refluxing a solution of amine 1 in pyridine
with the phosphorylating agent in the presence of triethyꢀ
lamine, which is much more basic than pyridine as the
hydrogen chloride acceptor (method А). However, it apꢀ
peared that, although this method affords phosphorylꢀ
amides 3a—g in high (71—83%) yields (Table 1), the yield
of amide 3h is substantially lower (45%); moreover, atꢀ
tempts to prepare phosphorylamides 3i,j according to the
method A failed because the corresponding starting phosꢀ
phoryl chlorides 2i,j undergo the destruction under these
conditions.
Hence, we developed an alternative, much milder apꢀ
proach to the synthesis of 2ꢀphosphorylaminoꢀ1,8ꢀnaphꢀ
thyridines 3 based on the reaction of phosphoryl chlorides
2 with a suspension of aminonaphthyridine 1 in chloroꢀ
form in the presence of triethylamine under heating (methꢀ
od B). Under these conditions, we succeeded in preparing
phosphoramides 3i,j and synthesized compounds 3a—h in
higher yields (the yield of phosphoramide 3h was substanꢀ
tially higher) than those obtained according to the method
А (see Table 1).
2,3
R
R´
2,3
R
R´
a
b
c
d
e
Ph
OPh
OC6H4Meꢀo
OC6H4Meꢀm OC6H4Meꢀm
OC6H4Meꢀp OC6H4Meꢀp
Ph
OPh
OC6H4Meꢀo
f
Ph
OPh
Ph
Me
OEt
Me
Me
OEt
OEt
OEt
g
h
i
j
mercially available reactants,15 as the starting aminoꢀsubꢀ
stituted naphthyridine and various phosphoric, phosphoꢀ
nic, and phosphinic acid monochlorides (2a—j) as phosꢀ
phorylating agents. This allowed us to widely vary the
nature of the substituents at the ligand phosphoryl group.
All 2ꢀ(Nꢀphosphorylamino)ꢀsubstituted 1,8ꢀnaphthyꢀ
ridines 3a—j are airꢀstable white or paleꢀyellow solid comꢀ
pounds, which are readily soluble in such organic solvents
as N,Nꢀdimethylformamide, dimethyl sulfoxide, pyridine,
Table 1. Yields, melting points, and elemental analysis data for naphthyridines 3
Comꢀ
pound
Yield
(%)
M.p./°C
Found
Calculated
Molecular
formula
(%)
N
C
H
P
3a
3b
3c
3d
3e
3f
86 (78)*
80 (71)
82 (80)
80 (74)
84 (83)
83 (72)
79 (74)
78 (45)
82 (0)
191—192
67—68
70.85
70.77
65.18
65.18
66.37
66.50
66.61
66.50
66.42
66.50
65.74
65.59
62.14
62.38
63.40
63.34
55.83
55.91
54.55
54.36
5.29
5.40
5.03
4.97
5.49
5.58
5.52
5.58
5.60
5.58
5.80
5.83
5.49
5.54
5.94
5.91
6.44
6.50
6.41
6.52
11.30
11.25
10.21
10.37
9.70
9.69
9.74
9.69
9.78
8.45
8.30
7.46
7.64
7.10
7.15
7.23
7.15
7.07
7.15
9.67
9.95
9.43
9.46
9.01
9.07
10.97
11.09
10.10
10.01
C22H20N3OP
C22H20N3O3P
C24H24N3O3P
C24H24N3O3P
C24H24N3O3P
C17H18N3OP
C17H18N3O2P
C18H20N3O2P
C13H18N3O2P
C14H20N3O3P
138—139
98—99
127—128
229—230
186—187
98—99
9.69
13.50
13.50
12.75
12.84
12.35
12.31
15.11
15.05
13.66
13.59
3g
3h
3i
203—204
117—118
3j
71 (0)
*The yields of naphthyridines 3 synthesized according to the method А are given in parentheses.

2ꢀ(NꢀPhosphorylamino)ꢀ1,8ꢀnaphthyridines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
1447
benzene, and chloroform and are poorly soluble in hexꢀ
ane, diethyl ether, and water. The purity and the strucꢀ
tures of the reaction products were confirmed by elemenꢀ
environment of the phosphorus atom. The 1H NMR specꢀ
tra have several types of signals. Thus, the lowꢀfield sigꢀ
nals characterize the presence of the naphthyridine moiꢀ
ety, and the highꢀfield signals correspond to aliphatic subꢀ
stituents at the phosphorus atom, as well as to the methyl
groups at the naphthyridine moiety. In addition, signals
1
tal analysis and NMR spectroscopy (31P{1H} and H)
(Table 2). In all cases, the 31P{1H} NMR spectra show
a singlet in the region characteristic of the corresponding
Table 2. Massꢀspectrometric data and the 31P{1H} and 1H NMR spectroscopic data (CDCl3) for naphthyridines 3
Comꢀ
pound
MS, m/z (Irel (%))
NMR, δ (J/Hz)
31Р
1H
3a
373 [M]+ (55.5), 372 [M – H]+ (100), 296 [M – C6H5]+
(42.6), 278 [C16H13N3P]+ (6.6), 248 [C16H13N3]+ (19.5),
218 [C12H13NOP]+ (17.8), 199 [C12H10NP]+ (6.4)
16.8 2.49 (s, 3 Н, СН3), 2.51 (s, 3 Н, СН3), 7.08 (s, 1 Н,
Нnaphth(6)), 7.26 (d, 1 Н, Нnaphth(3), J = 9.1), 7.46—7.54 (m,
6 Н, mꢀPh + pꢀPh), 7.81—7.86 (m, 4 Н, oꢀPh),
8.23 (d, 1 Н, Нnaphth(4), J = 9.1)
3b
3c
3d
405 [M]+ (8.0), 404 [M – H]+ (13.5), 328 [M – C6H5]+
(6.2), 312 [M – C6H5O]+ (93.1), 294 [M – (C6H5O +
+ H2O)]+ (22.5), 249 [C12H12NO3P]+ (100),
248 [C12H11NO3P]+ (86.3), 218 [C11H7O3P]+ (36.2)
433 [M]+ (15.2), 326 [M – C7H7O]+ (62.7),
–3.0 2.52 (s, 3 Н, СН3), 2.55 (s, 3 Н, СН3), 6.94 (s, 1 Н,
Нnaphth(6)), 7.10—7.13 (m, 3 Н, Нnaphth(3) + pꢀPh),
7.27—7.28 (m, 8 Н, oꢀPh + mꢀPh), 7.95 (dd, 1 Н, Нnaphth(4),
2J = 9.4, 3J = 1.8)
–2.7 2.27 (s, 6 H, C6H4CH3), 2.51 (s, 3 Н, Menaphth), 2.55 (s,
3 Н, Menaphth), 6.93 (s, 1 Н, Нnaphth(6)), 6.99—7.16 (m, 7 Н,
Нnaphth(3) + mꢀC6H4CH3 + pꢀC6H4CH3), 7.37 (d, 2 Н,
oꢀC6H4CH3, J = 8.0), 7.94 (d, 1 Н, Нnaphth(4), J = 9.4)
–3.5 2.28 (s, 6 H, C6H4CH3), 2.51 (s, 3 Н, Menaphth),
2.54 (s, 3 Н, Menaphth), 6.91 (d, 2 Н, mꢀC6H4CH3, J = 7.1),
6.93 (s, 1 Н, Нnaphth(6)), 7.05—7.17 (m, 7 Н, Нnaphth(3) +
+ oꢀC6H4CH3 + pꢀC6H4CH3), 7.95 (d, 1 Н, Нnaphth(4),
J = 9.4)
308 [M – (C7H7O + H2O)]+ (20.4), 263 [C14H16O3P]+
(97.4), 262 [C14H15O3P]+ (100), 236 [C10H11N3O2P]+
(9.8), 218 [C10H19N3OP]+ (20.2)
433 [M]+ (6.1), 326 [M – C7H7O]+ (66.9),
308 [M – (C7H7O + H2O)]+ (16.1), 263 [C14H16O3P]+
(93.6), 262 [M – C10H9N3]+ (100), 218 [M – 2 C6H4CH3]+
(23.3), 173 [C10H11N3]+ (8.7)
3e
3f
433 [M]+ (10.6), 326 [M – C7H7O]+ (54.3),
–3.2 2.27 (s, 6 H, C6H4CH3), 2.52 (s, 3 Н, Menaphth), 2.55 (s,
3 Н, Menaphth), 6.95 (s, 1 Н, Нnaphth(6), 7.04—7.16 (m, 9 Н,
Нnaphth(3) + C6H4CH3), 7.97 (d, 1 Н, Нnaphth(4), J = 9.4)
308 [M – (C7H7O + H2O)]+ (19.6), 263 [C14H16O3P]+
(100), 262 [M – C10H9N3]+ (83.7), 236 [C10H11N3O2P]+
(11.3), 218 [M – 2 OC6H4CH3]+ (20.0)
311 [M]+ (18.0), 310 [M – H]+ (19.9), 296 [M – CH3]+
(100), 278 [M – (CH3 + H2O)]+ (5.4), 234 [M – C6H5]+
(4.5), 218 [C11H13N3P]+ (18.5), 173 [C10H11N3]+ (9.6)
30.1 1.95 (d, 3 Н, Р—СН3, 2JHP = 14.4), 2.50 (s, 3 Н,
Menaphth), 2.59 (s, 3 Н, Menaphth), 6.94 (s, 1 Н, Нnaphth(6)),
7.20 (d, 1 Н, Нnaphth(3), J = 9.1), 7.41—7.51 (m, 3 Н,
oꢀPh + pꢀPh), 7.94 (d, 1 Н, Нnaphth(4), J = 9.1),
7.97—8.02 (m, 2 Н, mꢀPh)
3g
3h
326 [M]+ (2.3), 252 [M – C6H3]+ (9.6),
29.4 2.06 (d, 3 Н, Р—СН3, 2JHP = 17.6), 2.56 (s, 3 Н,
Menaphth), 2.65 (s, 3 Н, Menaphth), 7.00—7.06 (m, 2 Н,
mꢀPh), 7.05 (d, 1 Н, Нnaphth(3), J = 9.0), 7.11—7.15 (m, 4 Н,
oꢀPh + pꢀPh + Нnaphth(6)), 8.01 (d, 1 Н, Нnaphth(4), J = 9.0)
18.4 1.34 (t, 3 Н, О—СН2—СН3, J = 7.0), 2.49 (s, 3 Н,
Menaphth), 2.58 (s, 3 Н, Menaphth), 4.15—4.23 (m, 2 Н,
О—СН2—CH3), 6.94 (s, 1 Н, Нnaphth(6), 7.20 (d, 1 Н,
Нnaphth(3), J = 9.1), 7.38—7.43 (m, 2 Н, mꢀPh), 7.48 (m,
1 Н, pꢀPh), 7.88—7.97 (m, 3 Н, oꢀPh + Нnaphth(4))
250 [M – C6H5]+ (8.5), 249 [M – C6H6]+ (38.8),
235 [M – Н, C6H4O]+ (19.7), 234 [M – C6H5O]+ (100),
216 [M – (C6H5O + H2O)]+ (43.9), 173 [C10H11N3]+ (8.7)
341 [M]+ (11.6), 340 [M – H]+ (15.4), 312 [M – C2H5]+
(20.0), 297 [M – C2H4O]+ (11.4), 296 [M – C2H5O]+
(10.0), 294 [M – (C2H5 + H2O)]+ (19.8),
248 [C11H11N3O2P]+ (50.1), 236 [M – (C6H5 + C2H5)]+
(99.4), 220 [M – (C6H5 + C2H5O)]+ (90.3),
173 [C10H11N3]+ (100)
3i
3j
279 [M]+ (20.1), 250 [M – C2H5]+ (5.0),
29.5 1.26 (td, 3 Н, О—СН2—СН3, JНН = 7.1, JНР = 2.0),
1.90 (d, 3 Н, Р—СН3, 2JНР=17.6), 2.55 (s, 3 Н, Menaphth),
2.63 (s, 3 Н, Menaphth), 3.98—4.04 (m, 1 Н, О—СН2—СН3),
4.13—4.17 (m, 1 Н, О—СН2—СН3), 6.98 (s, 1 Н,
236 [M – (C2H4 + CH3)]+ (21.8), 235 [M – (C2H5 +
+ CH3)]+ (19.1), 220 [M – (C2H4O + CH3)]+ (100),
173 [C10H11N3]+ (60.2), 157 [C10H9N2]+ (8.2)
Н
naphth(6)), 7.25 (d, 1 Н, Нnaphth(3), J = 8.9), 8.07 (d, 1 Н,
naphth(4), J = 8.9)
Н
309 [M]+ (14.1), 281 [M – C2H4]+ (10.9),
265 [M – C2H4O]+ (4.2), 253 [M – 2C2H4]+ (4.7),
236 [C12H15N3O2P]+ (13.1), 201 [C12H15N3]+ (6.2),
173 [C10H11N3]+ (100)
1.8 1.32 (t, 6 Н, О—СН2—СН3, J = 7.0), 2.57 (s, 3 Н, Menaphth),
2.62 (s, 3 Н, Menaphth), 4.10—4.21 (m, 4 Н, О—СН2—СН3),
7.00 (s, 1 Н, Нnaphth(6), 7.27 (d, 1 Н, Нnaphth(3), J = 8.9),
8.10 (d, 1 Н, Нnaphth(4), J = 8.9)

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Lemport et al.
Table 3. Selected geometric parameters for two independent
molecule in the structure of 3j
assigned to aromatic substituents at the phosphorus atom
and a signal for the proton of the NH group can be obꢀ
served at low field depending on the type of the compound
(see Table 2).
Parameter
Bond
3j
3j´
Since the phosphorylamide derivatives of 1,8ꢀnaphꢀ
thyridine synthesized in the present work contain various
substituents at the phosphorus atom, these compounds
differ in stability. Hence, it was of interest to investigate
the stability of these compounds to electron impact.
The massꢀspectrometric study showed that naphthyriꢀ
dine 3a containing the diphenylphosphoryl group is most
stable to electron impact. The mass spectrum of this comꢀ
pound has the most intense molecular ion peak M+ and
the maximum related stabilizing effect giving the base ion
at m/z = 372 with the intensity of approximately 100%.
For compounds 3f and 3h (containing one phenyl group at
the phosphorus atom), this effect is much less pronounced.
In turn, the least intense molecular ions are observed for
naphthyridines 3b—e and 3g containing the phenoxy subꢀ
stituents (for naphthyridine 3g, the intensity is as low as
2.3%) and for compounds 3h—j containing the alkoxy
groups at the phosphorus atom.
d/Å
P(1)—O(1)
P(1)—O(2)
P(1)—O(3)
P(1)—N(3)
O(2)—C(11)
O(3)—C(13)
N(3)—C(1)
N(1)—C(1)
N(1)—C(8)
N(2)—C(8)
N(2)—C(7)
C(1)—C(2)
C(2)—C(3)
C(3)—C(4)
C(4)—C(5)
C(6)—C(7)
C(4)—C(8)
1.4745(13)
1.5665(13)
1.5652(13)
1.6457(14)
1.464(2)
1.460(2)
1.393(2)
1.321(2)
1.364(2)
1.369(2)
1.324(2)
1.428(2)
1.353(2)
1.425(2)
1.417(2)
1.410(2)
1.415(2)
1.4656(13)
1.5683(12)
1.5711(13)
1.6561(15)
1.443(2)
1.454(2)
1.389(2)
1.320(2)
1.362(2)
1.365(2)
1.323(2)
1.427(2)
1.354(3)
1.417(3)
1.422(2)
1.416(3)
1.424(2)
Angle
ω/deg
The main fragmentation pathways of the phosphorylꢀ
amide derivatives of naphthyridine were also investigated
by mass spectrometry. The analysis of the mass spectra
showed that the favorable fragmentation pathway for some
of the 1,8ꢀnaphthyridines synthesized in the present study
involves the elimination of one of the substituents (for
example, of the phenyl group) from the phosphorus atom
rather than the cleavage of the P—N bond, which is relaꢀ
tively labile in most cases (see Table 2). Thus, the intensiꢀ
ty of the ion corresponding to the elimination of one pheꢀ
nyl group from naphthyridine 3a is 42.6%. The intensity
of the ion at m/z = 296 that is formed as a result of the
elimination of the methyl group from compound 3f and
the intensity of the ion at m/z = 234 assigned to the elimiꢀ
nation of the phenoxy group from naphthyridine 3g are
100%. The intense ion peaks at m/z = 173, which are
indicative of the P—N bond cleavage, are observed only in
the mass spectra of naphthyridines 3h—j containing the
ethoxy groups at the phosphorus atom.
Naphthyridine 3j containing two ethoxy groups at the
phosphorus atom was studied by Xꢀray diffraction. Acꢀ
cording to the Xꢀray diffraction data, the bond lengths
and bond angles (Table 3) in the heteroaromatic moiety
are typical of this class of compounds.16 The deviations of
the atoms of the naphthyridine system from the mean
plane are, on the average, 0.02(1) and 0.04(1)Å for two
crystallographically independent molecules in the strucꢀ
ture of 3j. These data confirm the aromaticity of the phosꢀ
phorusꢀcontaining naphthyridine. The C—C bond lengths
of the methyl substituents in the naphthyridine moiety
and of the ethyl substituents at the phosphorus atom vary
from 1.487(3) to 1.509(3)Å. According to the Xꢀray difꢀ
fraction data (see Table 3), the P(1)—N(3) bond is single,
O(1)—P(1)—O(2)
O(1)—P(1)—O(3)
O(2)—P(1)—O(3)
O(1)—P(1)—N(3)
O(2)—P(1)—N(3)
O(3)—P(1)—N(3)
C(1)—N(1)—C(8)
N(1)—C(8)—N(2)
N(1)—C(8)—C(4)
C(8)—N(2)—C(7)
N(3)—C(1)—N(1)
N(3)—C(1)—C(2)
C(1)—C(2)—C(3)
C(2)—C(3)—C(4)
C(3)—C(4)—C(5)
C(4)—C(5)—C(6)
C(5)—C(6)—C(7)
115.95(7)
107.86(7)
107.55(7)
110.04(7)
103.70(7)
111.75(8)
117.06(14)
114.58(14)
123.29(14)
118.04(14)
118.80(14)
117.20(14)
118.90(15)
119.35(15)
123.78(15)
117.44(15)
120.49(15)
109.34(7)
116.18(7)
104.05(7)
116.61(8)
107.88(7)
101.73(7)
117.99(14)
114.93(15)
122.76(16)
117.65(15)
116.00(15)
120.55(15)
118.44(16)
120.46(16)
124.45(16)
117.12(16)
120.73(17)
thus allowing the rotation of the other atoms about this
bond and resulting in that the diethoxyphosphoryl fragꢀ
ments in two independent molecules 3j are in different
orientations with respect to the naphthyridine moiety
(Fig. 1). In molecule 3j (the atoms are unprimed), the
O(1)—P(1)—N(3)—C(1) torsion angle is 26.4(2)°, and
the ethoxy groups are on the opposite sides with respect to the
plane of the naphthyridine moiety, whereas the corresponꢀ
ding torsion angle in 3j´ (the atoms are primed) is 68.1(2)°,
and the substituents are on the same side of the heterocyꢀ
cle. The proton at the N(3) atom in molecules 3j or 3j´
and the N(1) atom are in the trans and cis positions with
respect to the N(3)—C(1) bond, respectively (see Fig. 1).
Due to the different orientation of the NH group with
respect to the heterocycle, molecules 3j and 3j´ form difꢀ

2ꢀ(NꢀPhosphorylamino)ꢀ1,8ꢀnaphthyridines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
1449
C(12)
C(14´)
C(11)
O(1´)
C(12´)
O(2´)
O(2)
O(1)
P(1´)
C(13´)
C(11´)
C(2´)
C(3´)
O(3´)
P(1)
N(3)
C(1)
N(3´)
C(1´)
O(3)
N(1)
C(13)
C(14)
N(2)
C(9´)
C(4´)
C(8´)
N(1´)
C(5´)
C(6´)
C(2)
C(3)
C(8)
C(10)
C(7)
N(2´)
C(4)
C(6)
C(7´)
C(10´)
C(5)
C(9)
Fig. 1. Structure of the tetramer formed by molecules 3j through hydrogen bonds (displacement ellipsoids are drawn at the 50%
probability level). The atomic numbering scheme is given only for the asymmetric unit cell. The hydrogen atoms, which are not
involved in the hydrogen bonding, are omitted. The hydrogen bonds are indicated by dashed lines.
ferent types of hydrogen bonds. Two molecules 3j form
a centrosymmetric dimer through two N(3)—H…O(1) hyꢀ
drogen bonds between the amino group and the oxygen
atom of the phosphoryl group (r(N…O) = 2.801(2) Å,
r(H…O) = 2.066 Å, and the N—H—O angle is 173°).
Each molecule 3j is linked to molecule 3j´ through the
N(3´)–H…N(2) hydrogen bond between the amino group
and the heterocycle (r(N…N) = 2.908(2) Å, r(H…N) =
= 2.142 Å, the N—H—N angle is 174°). As a result, the
crystal structure of 3j consists of tetramers formed through
strong hydrogen bonds (see Figs 1 and 2). The naphthyriꢀ
dine cores of molecules 3j´ are almost perpendicular to the
heterocycles of molecules 3j (the angle between the hetꢀ
erocycles is 89.82(2)°). In the crystals of 3j, in addition to
the hydrogen bonds, there are also stacking interactions
between the heterocycles of the molecules of one type
(between two molecules 3j or 3j´). In all cases, the naphꢀ
thyridine moieties that form stacking contacts are related
to each other by a center of inversion and, consequently,
are strictly parallel to each other (Fig. 2). In molecules 3j
and 3j´, the heterocycle—heterocycle distance is 3.35 and
3.47 Å, respectively. As a result, the structure of 3j consists
a
c
0
b
Fig. 2. Fragment of the crystal packing of 3j projected along the crystallographic a axis. The hydrogen atoms, which are not involved in
the hydrogen bonding, are omitted. The hydrogen bonds are indicated by dashed lines.

1450
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
Lemport et al.
–
β = 85.976(1)°, γ = 68.603(2)°, V = 1508.5(1) Å3, space group P1,
of layers perpendicular to the crystallographic a axis, which
are formed by the molecules linked together through hyꢀ
drogen bonds and stacking interactions.
To conclude, let us note that the synthetic approach
used in the present study is suitable for the preparation of
a wide range of phosphorusꢀ and nitrogenꢀcontaining
naphthyridine ligands, which, in principle, can act as effiꢀ
cient complexꢀforming agents for different metal cations,
including actinides and lanthanides.
Z = 4, dcalc = 1.362 g cm–3. A total of 14364 reflections were
collected on a Bruker Smart 1000 diffractometer at 120 K
(MoꢀKα radiation, 2θ
= 54.00°) from a single crystal of diꢀ
max
mensions 0.32×0.24×0.16 mm. The merging of equivalent reꢀ
flections gave 6567 independent reflections (Rint = 0.0187),
which were used for the structure solution and refinement. The
structure was solved by direct methods. All nonhydrogen atoms
were located in difference electron density maps and refined
anisotropically based on F2hkl. All hydrogen atoms were found in
difference electron density maps and refined isotropically using
a riding model. All calculations were carried out with the use of
the SHELXTL ver. 5.10 program package.23 The final R factors
were as follows: R1 = 0.0401 (based on Fhkl for 5407 reflections
with I > 2σ(I)), wR2 = 0.0962 (based on F 2hkl for all 6567 reflecꢀ
tions), GOOF = 1.001. The completeness of the data set was
99.8%, the number of parameters in the refinement was 387,
the maximum and minimum residual peaks were 0.359 and
–0.388 e Å–3, respectively.
Experimental
The 1H and 31Pꢀ{1H} NMR spectra were recorded on a Brukꢀ
1
er Avanceꢀ400 instrument operating at 400.13 MHz for H and
at 161.98 MHz for 31P at 298 K in CDCl3 using the residual
signals of the protons of the deuterated solvent as the internal
standard (1H) and of 85% H3PO4 as the external standard (31P).
The concentration of the solutions was 0.02 mol L–1
.
The mass spectra were recorded on a Finnigan Polaris Q
mass spectrometer (EI, 70 eV, the temperature of the ion source
was 250°C, a direct inlet probe (DIP) with programmed heating
of the ampoule from 50° to 100—150 °C). The assignment was
made taking into account the ion fragmentation scheme deterꢀ
mined by recording the mass spectra in the MSn mode (n = 1—5).
All operations were carried out under argon. The solvents
were saturated with argon, purified, and dried according to known
procedures.17 Diphenyl chlorophosphinate 2a, diphenyl chloroꢀ
phosphate 2b, methyl phenyl chlorophosphinate 2f, and diethyl
chlorophosphate 2j (Aldrich) were purified by distillation in vacuo.
2ꢀAminoꢀ5,7ꢀdimethylꢀ1,8ꢀnaphthyridine 1,15 bis(oꢀtolyl) chloꢀ
rophosphate 2c,18 bis(mꢀtolyl) chlorophosphate 2d,19 bis(pꢀtolyl)
chlorophosphate 2e,18 Oꢀphenyl methyl chlorophosphonate 2g,20
Oꢀethyl phenyl chlorophosphonate 2h,21 and Oꢀethyl methyl
chlorophosphonate 2i (see Ref. 22) were synthesized according
to known procedures.
Synthesis of 2ꢀ(Nꢀphosphorylamino)ꢀsubstituted 1,8ꢀnaphthyrꢀ
idines 3a—g (method А). The corresponding phosphoryl chloride
2 (5 mmol) was added dropwise to a solution of aminonaphthyriꢀ
dine 1 (867 mg, 5 mmol) and anhydrous triethylamine (606 mg,
6 mmol) in anhydrous pyridine (10 mL) at room temperature.
The reaction mixture was refluxed for 5 h, pyridine was removed
using a waterꢀjet vacuum pump, and the residue was dissolved in
CHCl3 (20 mL), washed with water (2×15 mL), dried over
MgSO4, and chromatographed on alumina (8 g) using CHCl3 as
the eluent. The solvent was removed from the eluate, and the
residue was recrystallized from tertꢀbutyl methyl ether.
The complete tables of the atomic coordinates, bond
lengths, and bond angles were deposited with the Camꢀ
bridge Structural Database (CCDC 710331).
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2ꢀ(NꢀPhosphorylamino)ꢀ1,8ꢀnaphthyridines
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Received December 22, 2008;
in revised form April 14, 2009