Synthesis and solution studies of Cu(II) complexes with pyridine derivatives of iminobisphosphonic acids

Article abstract of DOI:10.1016/j.ica.2010.09.045

New 2-pyridyl, 3-pyridyl and 4-pyridyl derivatives of iminobisphosphonic acid were prepared by addition of tris(trimethylsilyl)phosphite to the corresponding derivatives of pyridineimine-methylphosphonates 3 and subsequent methanolysis of the silylated pr

Full text of DOI:10.1016/j.ica.2010.09.045

Inorganica Chimica Acta 365 (2011) 391–399
Contents lists available at ScienceDirect
Inorganica Chimica Acta
journal homepage: www.elsevier.com/locate/ica
Synthesis and solution studies of Cu(II) complexes with pyridine derivatives
of iminobisphosphonic acids
a
b
b,
a,
⇑
⇑
_
Waldemar Goldeman , Monika Pyrkosz , Elzbieta Gumienna-Kontecka , Bogdan Boduszek
a
_
Department of Organic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspian´skiego 27, 50-370 Wroclaw, Poland
b Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie 14, 50-383 Wroclaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
New 2-pyridyl, 3-pyridyl and 4-pyridyl derivatives of iminobisphosphonic acid were prepared by addi-
tion of tris(trimethylsilyl)phosphite to the corresponding derivatives of pyridineimine-methylphospho-
nates 3 and subsequent methanolysis of the silylated products 4. Solution studies on the coordination
abilities of the ligands have shown that these compounds bind copper(II) ion through the tridentate
{N,O,O} mode, where Cu(II) is stabilized by two five-membered chelate rings. The complexes obtained
are very stable, with the pCu(II) value above 12, and therefore the ligands can be used as powerful che-
lating agents for copper ion.
Received 12 May 2010
Received in revised form 16 September
2010
Accepted 27 September 2010
Available online 12 October 2010
Keywords:
Ó 2010 Elsevier B.V. All rights reserved.
Iminobisphosphonic acids
Pyridine derivatives
Copper(II) complexes
Stability constants
Potentiometry
UV–Vis and EPR spectroscopy
1. Introduction
aminomethyl(phenyl)phosphinic acids [5c], aminophosphine
oxides [5d] and aminomethyl-H-phosphinic acids [5e], which are
Iminomethylenebisphosphonic acids have found applications
as chelating and complexing agents [1]. Most of them are per-
phosphonomethylated polyamines, for example, the ethylenedi-
aminetetramethylenephosphonic acid, sold as penta-sodium salt
by Monsanto (as DEQUEST 2046) and diethylenetriaminepentam-
ethylenephosphonic acid, sold as hepta-sodium salt (as DEQUEST
2066). Such phosphonylated polyamines are also used as seques-
tering agents [2a,b], anticorrosion agents [2c], ingredients of
coating bath compositions [2d] and precipitation inhibitors [2e].
Phosphonomethylated amines are generally effective ligands,
because they can coordinate metals like Zn, Mg, Ca, Cu, Co, Ni
and Mn [3]. These acids are also good inhibitors of corrosion [4a],
show surfactancy deflocculating properties likewise as its esters,
which additionally exhibit ability of solubilizing water in water-
immiscible solvents [4b–d]. In turn, for example, N,N-bis(phospho-
nomethyl)glycine is an active component of a plant growth
regulator, known as glyphosine and also as a ripening agent for
sugar cane (marketed by Monsanto as PolarisÒ) [4e,f].
structurally related to the iminobisphosphonates. Among consid-
ered iminobisphosphonates (the general formula in Fig. 1) up to
now there are no examples of pyridine derivatives in a chemical
literature. Therefore, we were looking for new methodology in
order to prepare such compounds, which could be then used as
new chelating agents for metal ions.
1.1. Synthesis of pyridine derivatives of iminobisphosphonic acids
In contrast to well known 1-aminoalkylphosphonic acids and
their N-substituted derivatives, few papers have been devoted only
to synthesis of iminomethylenebisphosphonic acids.
The simplest iminobismethylenephosphonic acid (R1 = R2 = R3 =
H) was first synthesized by Petrov et al. in 1959 [6]. Recently, prep-
arations of new iminobisphosphonic acids were elaborated as well
[7]. Some N-substituted (R1 = R2 = H, R3 = alkyl) derivatives were
prepared by known Mannich type reaction with use of primary ali-
phatic amine, formaldehyde and phosphorous acid, described by
Moedritzer and Irani [8] and others [9]. Formation of various
derivatives of iminobisphosphonic acid in reaction of alkylation
of primary amines with chloromethylphosphonic acid was also de-
scribed [10].
Few years ago, we described some 2-, 3- and 4-pyridyl deriva-
tives of aminomethylphosphonic acid [5a,b] and their esters [5a],
⇑
Corresponding authors. Fax: +48 71 3757342 (E. Gumienna-Kontecka), +48
713284064 (B. Boduszek).
In literature, there are only few examples of iminomethylenebis-
phosphonic acids possessing diversified substituents at a-position,
E-mail addresses: kontecka@wchuwr.pl (E. Gumienna-Kontecka), bogdan.
boduszek@pwr.wroc.pl (B. Boduszek).
0020-1693/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.ica.2010.09.045

392
W. Goldeman et al. / Inorganica Chimica Acta 365 (2011) 391–399
R1
R2
R2
N
NH2
R1
R2
N
Py
CH2Cl2
P(OEt)3 + 7TMSBr
Py
O
PO3H2
PO3H2
R3
PO3Et2
PO3Et2
1a-c
2a-c
3a-i
R1
Py
Py
PO3TMS2
PO3TMS2
PO3H2
PO3H2
Fig. 1. General formula of iminobisphosphonic acids.
MeOH/Et2O
TMS
N
HN
R1
R2
5a-i
R1
R2
i.e. tetraethyl esters of N-phosphonomethylated 1-(alkylamino)-
alkylphosphonates (R1 = alkyl or Ar, R2 = R3 = H) [11a], and tetra-
alkyl esters of iminobis(2-methylpropyl)bisphosphonic acid
(R1 = R2 = i-Pr, R3 = H), which were prepared in reaction of dialkyl
N-isopropylidene-1-amino-2-methylpropylphosphonate with dial-
kyl phosphonates in the presence of sodium alkoxide [11b]. In turn,
Soroka and Kołodziejczyk [12a] reported synthesis of symmetrical
iminobisphosphonic acids by a sequence of reaction of hydrobenza-
mide with diethyl phosphonate, or by use of hydrobenzamide with a
mixture of PCl3–acetic acid. Soroka and Kołodziejczyk [12a] also
described reaction of dialkyl N-arylidene 1-amino-1-aryl-methyl-
phosphonate with dialkyl phosphonates, or with a mixture of
PCl3–acetic acid, to give corresponding symmetrical and unsym-
metrical aryliminobisphosphonic acids. The needed reagents,
i.e. the N-arylidene 1-amino-1-arylmethylphosphonates were
obtained in reaction of 1-amino-1-aryl-methylphosphonates with
some aromatic aldehydes, or in reaction of hydrobenzamide with
dialkylphosphonates [12b,c].
Other authors [13] described synthesis of some tetra-alkyl esters
of unsymmetrical iminobismethylenephosphonic acid in reaction
of benzylideneaminocarboxylate salts with dialkyl chlorophosph-
ites. Authors believed that reaction came through a stage with dial-
kyl N-alkylidene 1-amino-1-phenylmethylphosphonate, which
reacted with dialkyl phosphonate, formed in situ in the reaction
mixture. Some specific iminobisphosphonic acids, like for example;
the 2,6-piperidine and 2,5-pyrrolidine bisphosphonic acids, synthe-
sized for biological purposes, were also reported [14].
4a-i
Scheme 2.
Table 1
Pyridine iminobisphosphonic acids 5.
R1
R2
Py
Yield (%)a
m.p. (°C)
de (%)b
5a (L1)
5b (L2)
5c (L3)
5d (L4)
5e (L5)
5f (L6)
5g (L7)
5h (L8)
5i (L9)
H
H
H
Me
Me
Me
Ph
Ph
Ph
H
H
H
2-Py
3-Py
4-Py
2-Py
3-Py
4-Py
2-Py
3-Py
4-Py
77
77
71
67
91
73
74
81
83
174–177
244–246
186–188
190–194
166–170
172–173
194–198
96–98
–
–
–
–
–
–
73
97
61
Me
Me
Me
H
H
H
190–196
a
Yield calculated after recrystallization of the crude product.
de (%) based on 31P NMR.
b
nate, where the expected product was obtained with ꢀ40% yield.
These results showed that in contrast to simple N-pyridylideneam-
ines, the addition reaction of N-pyridylidene 1-aminophospho-
nates with dialkylphosphonates underwent with a difficulty, and
the reaction was hard to recognize (mainly unidentified dark-
colored products were formed).
In order to resolve this issue, we have decided to use the silylat-
ed esters of prosphorous acid (H3PO3) to above addition reaction.
According to the literature data [17] the silylated esters were used
for an effective phosphonylation of various aldimines. Such addi-
tion reactions proceeded in mild conditions at ambient tempera-
ture [17].
In this case, tris(trimethylsilyl)phosphite was generated in situ
from triethylphosphite and trimethylsilylbromide (TMSBr). Using
an excess of TMSBr in the reaction mixture (Scheme 2), the prod-
ucts were formed as transestrificated phosphonic silyl esters
[tetra(trimethylsilyl) esters 4]. In the next stage, addition of meth-
anol caused dealkylation of the silyl esters 4 and formation of the
corresponding iminobisphosphonic acids 5, which were separated
as crystalline products, with a good yield and purity (Scheme 2,
Table 1).
In the case of 5h, the iminobisphosphonic acid was isolated
practically as one, single diastereoizomer (Table 1), according to
NMR data. In turn, the corresponding phosphonic acid 5g and 5i
were mixtures of two diastereomers, with considerable predomi-
nance of one diastereoisomer. It is necessary to mention, that these
diastereomers are really enantiomeric mixtures, due to the fact,
that starting materials 3g, h and i were also racemic mixtures.
2. Results and discussion
2.1. Synthesis
Based on literature data, devoted to N-arylidene-1-amin-
oalkylphosphonates [15,16], we have decided to use easy available
dialkyl 1-aminoalkylphosphonates and appropriate pyridine
aldehydes for synthesis of the desired N-pyridylidene 1-
aminoalkylphosphonates.
First, we examined the reaction of diethyl N-(40-pyridylidene)-
1-amino-1-phenylmethylphosphonate with diethyl phosphonate
(Scheme 1). After 8 h of boiling of the reactants in toluene we
found, that the expected product was formed in ꢀ30% yield,
according to 31P NMR spectra of the reaction mixture (Scheme 1).
According to the NMR, the final reaction mixture contained a large
number of unidentified products and some unreacted starting
materials. Similar results were obtained in the case of synthesis
of diethyl N-(20-pyridylidene)-1-amino-1-phenylmethylphospho-
Py
O
P
PO3Et2
PO3Et2
N
Py
OEt
OEt
toluene
unidentified
products
HN
Ph
H
2.2. Solution studies
8h reflux
PO3Et2
To evaluate the coordination properties of the studied ligands
(L1–L9, Table 1, Scheme 2) towards metal ions, first it was neces-
sary to determine their acid–base properties. The fully protonated
forms of the ligands (H6L2+) possess six dissociable protons (one at
the imino nitrogen, two at each phosphonic function and one at the
Py=2-Py, 4-Py
3d, f
30-40%
4` d,f
Scheme 1. Reaction of diethyl N-(pyridylidene)-1-amino-1-phenylmethylphosph-
onate with diethyl phosphonate.

W. Goldeman et al. / Inorganica Chimica Acta 365 (2011) 391–399
393
Table 2
Protonation (log bH) and stability constants (log b) of copper(II) complexes with iminobisphosphonic acids L1–L9 in aqueous solution.a
Assignments
Compound
L1
L2
L3
L4
L5
L6
L7
L8
L9
log bH1
log bH2
log bH3
log bH4
9.98(1)
9.41(1)
9.11(1)
11.86(3)
18.09(3)
23.11(3)
25.11(3)
10.65(1)
16.85(2)
21.96(2)
25.08(2)
10.43(2)
16.61(4)
22.10(3)
25.26(3)
9.59(3)
8.83(1)
8.68(1)
16.07(1)
21.07(1)
22.84(2)
15.44 (1)
20.47(1)
23.69(1)
15.18(1)
20.45(1)
23.79(1)
16.25(4)
21.62(5)
22.57(1)
15.50 (2)
20.80(2)
22.39(4)
15.40(2)
20.98(1)
23.02(3)
log KH (NH2
)
þ
9.98
6.09
5.00
1.77
9.41
6.03
5.03
3.22
22.11(2)
18.63(3)
13.98(3)
3.23(4)
–
–
–
–
–
9.11
6.07
5.27
3.34
22.03(2)
18.21(5)
12.99(8)
2.53(10)
–
–
–
–
–
11.86
6.23
5.02
2.00
24.40(1)
20.99(1)
16.08(1)
6.41(2)
–
–
–
–
–
10.65
6.20
5.11
3.12
23.30(1)
19.62(1)
14.74(2)
4.30(2)
–
–
–
–
–
10.43
6.18
5.49
3.16
23.36(2)
19.63(4)
14.43(7)
3.77(10)
–
–
–
–
–
9.59
6.66
5.37
<1
23.12(6)
19.50(7)
14.17(10)
4.27(15)
–
–
–
–
8.83
6.67
5.33
1.59
20.96(3)
17.51(2)
12.66(3)
2.32(3)
–
–
–
–
–
8.68
6.72
5.58
2.04
21.59(3)
17.94(2)
12.53(3)
2.20(4)
–
–
–
–
–
log KH (PO3Hꢁ)
log KH (PO3Hꢁ)
log KH (NHPyr
log b [CuH2L]
log b [CuHL]ꢁ
log b [CuL]2ꢁ
)
+
21.73(6)b,c
18.64(4)b
13.20(7)b
3.47(10)b
42.26(3)c
37.59(4)c
31.44(6)c
23.95(4)c
14.68(7)c
3.09
log b [CuL(OH)]3ꢁ
log b [CuH4L2]2ꢁ
log b [CuH3L2]3ꢁ
log b [CuH2L2]4ꢁ
log b [CuHL2]5ꢁ
log b [CuL2]6ꢁ
–
pK
pK
pK
3.48
4.65
10.75
3.82
5.22
10.46
3.41
4.91
9.67
3.68
4.88
10.44
3.73
5.20
10.66
3.62
5.33
9.90
3.45
4.85
10.34
3.65
5.41
10.33
½CuH2Lꢂ
ꢁ
5.44
9.73
½CuHLꢂ
2ꢁ
½CuLꢂ
pK
pK
pK
pK
S
4.67
6.15
7.49
9.27
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
2ꢁ
3ꢁ
4ꢁ
½CuH4L2
½CuH3L2
½CuH2L2
ꢂ
ꢂ
ꢂ
5ꢁ
½CuHL2
ꢂ
1.82b, 1.91c
1.92
456
0.73
472
1.58
437
1.23
458
1.03
430
1.11
447
1.76
462
1.20
446
Number of points
176b, 161c
a
b
C
I = 0.1 M (NaClO4), T = 25.0(2) °C. The reported errors on log b are given as 1r.
Stability constants calculated for metal-to-ligand molar ratio 1:1.
Stability constants calculated for metal-to-ligand molar ratio 1:2. S = sample standard deviation.
7x103
3.0
(a)
(b)
6x103
5x103
4x103
3x103
2x103
1x103
0
(2)
2.5
2.0
1.5
1.0
0.5
0.0
[H4L]
(1)
(2)
(1)
[H3L] -
[HL]3-
[L]4-
[H2L]2-
200
220
240
260
280
300
200
220
240
260
280
300
Wavelenght [nm]
Wavelenght [nm]
Fig. 2. (a) Absorption spectrophotometric titration vs. pH of the free L5 ligand and (b) electronic spectra of the protonated species of L5. I = 0.1 M (NaClO4); T = 25.0(2) °C;
[L5] = 4.18 ꢃ 10ꢁ3 M; (1) pH 2.03; (2) pH 10.61.
pyridine moiety), however not all of them could be determined
under our experimental conditions. The protonation constants
determined are given in Table 2.
and the latter comes from an electron-withdrawing effect of the
phenyl ring. Two further constants, with log K ꢀ6 and log K ꢀ5,
2ꢁ
correspond to stepwise protonation of two PO3 groups. The sec-
For all nine ligands, the most basic constant corresponds to the
protonation of the nitrogen of the secondary amino group. The
log K for this constant is >9 for L1–L3 ligands. Substitution of hydro-
gens (R1 = R2 = H in L1–L3) by methyl groups (R1 = R2 = CH3) in
ligands L4–L6, increases the imino protonation constant of about
1 log unit, while the introduction of the phenyl ring (R1 = Ph in
L7-L9) decreases this constant of about 0.4–0.6 log units. The first
effect is due to an electron donating properties of the alkyl group
ond protonation of each PO3Hꢁ group occurs much below pH 2 and
constants corresponding to these processes were not determined
under our experimental conditions. The value of protonation
constant of the pyridine nitrogen depends on its position. In the
2-Py analogues the log K is 1.77 for L1, 2.00 for L4 and below 1
for L7. In 3- and 4-Py analogues with R1 = R2 = H and R1 = R2 =
CH3 it exceeds 3 and for phenyl substituted ones, R1 = Ph, it is about
1.5 log unit lower (Table 2). The possibility of the formation of an

394
W. Goldeman et al. / Inorganica Chimica Acta 365 (2011) 391–399
Table 3
Comparison of the successive protonation constants determined by potentiometry and UV–Vis spectrophotometry.a
Ligands
L3
L4
L5
L7
Potentiometry
UV–Vis
Potentiometry
UV–Vis
Potentiometry
UV–Vis
Potentiometry
UV-Vis
log KH (NH2
)
9.11(1)
6.07(1)
5.27(1)
3.34(1)
8.94(6)
6.0(1)
5.2 (1)
3.4(2)
11.86(3)
6.23(3)
5.02(3)
2.00(3)
–
10.65(1)
6.20 (2)
5.11(2)
3.12(2)
10.8(3)
6.8(4)
5.3(4)
3.0(4)
9.59(3)
6.66(4)
5.37(5)
–
9.50(2)
6.7(2)
5.6(2)
–
þ
log KH (PO3Hꢁ)
6.3(4)
5.1(6)
1.7(6)
log KH (PO3Hꢁ)
log KH (NHPyr
)
+
a
I = 0.1 M (NaClO4), T = 25.0(2)°C. The reported errors on log K are given as 1r.
16
14
12
10
8
9.0
8.9
8.8
8.7
8.6
8.5
8.4
8.3
8.25
N
(b)
(a)
11
N
CH3
CH3
PO3H2
CH
PO3H2
CH
H2O3P CH2
CH3
H2O3P CH2
NH
NH
CH3
10
9
8.00
7.75
7.50
6
8
4
7
2
0
12
6
0
1
2
3
4
5
6
7
8
9
10
11
0
1
2
3
4
5
6
pH*
7
8
9
10
11
12
pH*
31
4
Fig. 3. 1H h and P d NMR titration curves as a function of pH (pH not corrected for the isotopic effect) performed for L (a) and L6 (b) ligands.
*
intramolecular hydrogen bonding between the 2-pyridine nitrogen
and phosphonic moiety explains its lower acidity in comparison to
the 3- and 4- analogues.
In order to confirm the protonation constants we have used a
fruitful combination of potentiometry and absorption spectropho-
tometry. The protonation processes of the studied ligands are re-
All nine ligands have three major binding sites centered at oxy-
gen atoms of two phosphonic groups and amino nitrogen donor.
There is also an alternative binding site at the pyridine nitrogen,
however it might be competitive only in 2-Py analogues. In
3- and 4-Py derivatives this nitrogen is not able to bind to metal
ions sitting at the amino-phosphonate binding site of the same
ligand molecule, yet it can become a bridging moiety in the dimeric
species [19b]. So as to define the solution equilibria between Cu(II)
and the studied ligands and to characterize species formed in solu-
tion we have performed potentiometric titrations supported by
spectroscopic (UV–Vis and EPR) characterization.
flected by significant shifts of the pyridine n ? p
* transitions
centred at about 265 nm (Fig. 2a). The statistical processing [18]
of the pH-spectrophotometric data led to the determination of four
protonation constants over the six existing ones. The protonation
of the imino group causes the hypso- and hyperchromic shifts of
the main band. Upon further protonations of the phosphonic
functions and the pyridine moiety, the band of 265 nm experi-
enced additional hypsochromic shifts. The protonation constants
obtained by potentiometric and spectrophotometric titrations
agree very well and are presented in Table 3 for L3, L4, L5 and L7
chosen as examples representing each group of ligands. The
electronic spectra of the corresponding protonated species are pre-
sented in Fig. 2b for L5.
Due to solubility reasons pH*-NMR titrations (pH* means pH
not corrected for the isotopic effect) were performed only for L4
and L6 ligands. The goal of the experiments was not to determine
all protonation constants of the ligands but only to confirm their
protonation scheme, especially the difference between protonation
of pyridine nitrogen in 2- and 3-/4-derivatives. As it is shown in
Fig. 3 the chemical shifts of the protons H3 of the pyridine moiety,
as well as phosphorus of phosphonate moiety adjacent to the pyr-
idine moiety follow the deprotonation processes underlying the
difference of ortho and meta/para substitution.
For all ligands, calculations based on potentiometric data sug-
gest formation of monomeric species with various protonation
states. Only for L1 additional bis-complexes could be observed
when an excess of ligand was used in solution. Neither dimeric,
nor other polynuclear species were detected. The respective stabil-
ity constants (logb) are reported in Table 2 together with the con-
stants corresponding to the successive deprotonation of the
complexes. Ligands L1–L9 form identical monomeric complexes
and their stability and pH-distribution will be discussed on one
example: Cu(II)–L3 system. The first species formed in solution is
a neutral complex [CuH2L]. The UV–Vis absorption d–d band cen-
tered at 758 nm with e
of about 50 Mꢁ1 cmꢁ1 (Table 4) can indicate
that in this species one nitrogen donor besides oxygen atoms are
bound to copper ion. Potentiometry based stoichiometry suggests
that one oxygen atom may come from one phosphonate unit while
the other phosphonate group is monoprotonated and not bound,
{CuN(imino)O(PO3Hꢁ)}. In the case of no involvement of the imino
group in the copper coordination, and binding by two monoproto-
nated phosphonic units (PO3Hꢁ), the absorption band should be
centered at about 800 nm [21]. The {CuN(imino)O(PO3Hꢁ)} coordi-
nation is also supported by EPR spectra with g|| = 2.344
and A|| = 138 G (Table 4). The deprotonation of [CuH2L] to [CuHL]ꢁ
is accompanied by slight blue-shift of the d–d bands, as well
Therefore the spectroscopic characterization fully confirms the
potentiometric results and the attribution of the protonation con-
stants (Table 2, Fig. 3). Moreover, all the observed values match
well with that determined previously for analogues aminomono-
[19] or aminodiphosphonic acids [3c,20].

W. Goldeman et al. / Inorganica Chimica Acta 365 (2011) 391–399
395
[CuL]2-
Table 4
100
Spectroscopic characteristics of Cu(II) complexes.
Ligand
Species
UV–Visa
EPR
[CuH2L]
[CuL(OH)]3-
(Mꢁ1 cmꢁ1
)
AII/G
gII
80
k (nm)
e
[CuHL]-
L1
[CuH2L]
675
614
303
605
303
604
305
596
305
598
305
756
738
730
708
758
740
720
718
744
747
732
680
770
741
724
720
749
736
725
719
743
743
734
695
758
746
735
713
775
762
727
714
60
63
163
182
2.296
2.104
[CuH4L2]2ꢁ
1580b
52
60
40
20
0
[CuH3L2]3ꢁ
[CuH2L2]4ꢁ
[CuHL2]5ꢁ
[CuL2]6ꢁ
185
185
187
187
2.102
2.101
2.098
2.097
1710b
57
Cu(II)free
1950b
81
2265b
77
2510b
48
L2
L3
L4
L5
L6
L7
L8
L9
[CuH2L]
139
153
162
155
138
141
158
156
155
158
158
155
148
158
158
155
150
150
158
2.342
2.295
2.294
2.287
2.344
2.395
2.289
2.287
2.286
2.283
2.279
2.280
2.327
2.294
2.290
2.292
2.317
2.308
2.290
[CuHL]ꢁ
[CuL]2ꢁ
53
56
54
49
55
56
57
81
83
81
77
55
57
58
53
59
59
61
60
77
69
75
83
53
57
55
45
43
53
55
51
3
4
5
6
7
8
9
10
11
[CuL(OH)]3ꢁ
[CuH2L]
pH
Fig. 4. Species distribution diagram for the Cu(II)–L3 system ([Cu(II)] = 10ꢁ3 M,
metal-to-ligand molar ratio 1:2).
[CuHL]ꢁ
[CuL]2ꢁ
[CuL(OH)]3ꢁ
[CuH2L]
[CuHL]ꢁ
[CuL]2ꢁ
N
[CuL(OH)]3ꢁ
[CuH2L]
[CuHL]ꢁ
[CuL]2ꢁ
[CuL(OH)]3ꢁ
[CuH2L]
O
O
NH
P
P
[CuHL]ꢁ
[CuL]2ꢁ
O-
-O
Cu
H2O
O
[CuL(OH)]3ꢁ
[CuH2L]
O
168
173
147
142
151
153
140
131
148
153
162
146
2.167
2.130
2.180
2.178
2.319
2.308
2.314
2.324
2.328
2.314
2.287
2.302
[CuHL]ꢁ
[CuL]2ꢁ
Scheme 3. Schematic representation of the proposed structure of the [CuL]2ꢁ
complex of L3.
[CuL(OH)]3ꢁ
[CuH2L]
[CuHL]ꢁ
[CuL]2ꢁ
100
[CuL(OH)]3ꢁ
[CuH2L]
[CuL2]6-
[CuHL]ꢁ
[CuL]2ꢁ
[CuHL2]5-
80
[CuH3L2]3-
[CuL(OH)]3ꢁ
[CuH2L2]4-
[CuH2L]
[CuH4L2]2-
a
d–d.
b
60
LMCT transitions. The ligands’ bands are not shown. Experimental errors on
2 nm and 5%.
kmax
=
e
Cu(II)free
40
as increase of A|| and decrease of g|| (Table 4), indicating involve-
ment of another phosphonate oxygen in copper coordination,
{CuN(imino)O(PO32ꢁ)O(PO3Hꢁ)}. The deprotonation constants
20
0
corresponding to this process, pKCuH L, is significantly lower then
2
the corresponding one in the free ligand (3.82 versus 5.27, Table 2).
Further deprotonation leads to the [CuL]2ꢁ complex with similar
tridentate coordination. Any additional band, like LMCT
ꢀ300 nm, indicating involvement of the pyridine nitrogen in the
metal coordination was not observed [22]. Above pH 9 the hydro-
lytic [CuL(OH)]3ꢁ complex starts to be formed, where the deproto-
nation of equatorially metal-bound water occurs. This is reflected
by slight hyper- and hypsochromic shift of d–d bands, as well as
changes in EPR parameters (Table 4).
3
4
5
6
7
8
9
10
11
pH
Fig. 5. Species distribution diagram for the Cu(II)–L1 system ([Cu(II)] = 10ꢁ3 M,
metal-to-ligand molar ratio 1:2).
large steric hindrance and electrostatic repulsion coming from oxy-
gen atoms, what prevents binding of the second ligand. Similar
complexes were previously observed by Kurzak et al. [3c] where
the secondary imino moiety was substituted by various functional
groups.
The distribution diagram of the Cu(II) complexes with L3 given
in Fig. 4 shows that the [CuL]2ꢁ species predominates over a wide
range of pH. The schematic representation of the structure pro-
posed for this complex is given in Scheme 3.
The formation of equimolar complexes with the studied diph-
osphonates results from the fact that the ligands are tridentate
and may form two five-membered chelate rings with coordinated
Cu(II) ion. Moreover, highly charged deprotonated ligands have a
For L1, in solutions with excess of ligand, additional set of spe-
cies was calculated. Apart [CuH2L] present in acidic solutions, for-
mation of variously protonated bis complexes ([CuHnL2], n = 0–4)
was observed up to pH 11 (Table 2, Fig. 5). Although stability con-
stant of the [CuH2L] complex is similar to analogues complexes of

396
W. Goldeman et al. / Inorganica Chimica Acta 365 (2011) 391–399
Table 5
pCu(II) values for various aminophosphonic acids.a
5). When pyridine moiety is in 2-position this effect is not observed
(L7 versus L6 [19b]). Albeit the pCu parameter in both cases is very
similar, it comes from completely different coordination mode. In
L7 the same stability is obtained by one chelating molecule instead
of two L6 ligands [19b] binding one metal ion, with the former
being much more desirable feature in design of efficient metal
chelators.
Ligand
L1
pCu(II)
Reference
This work
11.55b
7.53c
12.89
12.20
12.54
12.41
12.32
12.86
12.09
12.10
10.40
10.34
11.60
7.34
L2
L3
L4
L5
L6
L7
L8
L9
4
‘‘
‘‘
‘‘
‘‘
‘‘
‘‘
‘‘
‘‘
3. Conclusions
A series of new pyridine iminobisphosphonic acids were pre-
pared by one-pot procedure starting from appropriate diethyl
aminoalkylphosphonates and pyridine aldehydes, followed by a
mixture of triethyl phosphite and bromotrimethylsilane. After
work-up (treatment with methanol), the pyridine iminobisphos-
phonic acids 5 were isolated with high yields and purity.
Ref. [3]c
Ref. [3]c
Ref. [19]b
Ref. [19]b
6
L6
L8
a
pCu(II) = ꢁlog[Cu(II)]free at pH 7.4 for [Cu(II)] = 10ꢁ6 M and
[L] = 10ꢁ5 M. Abbreviations used: 4, N-methyliminobis(methyl-
enephosphonic) acid; 6, N-3-picolyliminobis(methylene-pho-
phonic) acid; L6, N-2-pyridylmethyl [N-(benzyl)amino]
phosphonic acid; L8, 4-pyridyl-methyl [N-(benzyl)amino] phos-
phonic acid.
The obtained compounds 5a–i (as ligands L1–L9) were evaluated
for coordination of Cu(II) ions. For all ligands, solution studies sug-
gest formation of monomeric species with various protonation
states, where copper(II) coordination is realized by nitrogen atom
of the imino group supported by two oxygens from two different
phosphonic units. Although the pyridine moiety is not participat-
ing in copper binding, the ligands are found to be better chelators
than previously designed iminobisphosphonic ligands substituted
at the secondary amino moiety.
b
pCu(II) calculated for metal-to-ligand molar ratio 1:1.
1:2.
c
other ligands, spectroscopic parameters indicate involvement of
pyridine, apart imino nitrogen, in copper binding (Table 4). Forma-
tion of 1:2 complex species distinctly shifted the EPR parameters
to g|| = 2.10 and A|| = 185 G and d–d transitions to about 600 nm
4. Experimental
4.1. General
(Table 4). Additionally
a new band at 305 nm with emax =
1250 Mꢁ1 cmꢁ1 appeared, which may correspond to Npyr ? Cu(II)
charge transfer transition (LMCT) [22] Therefore the [CuH4L2]2ꢁ
complex very likely have the four nitrogen coordination, which
possibly might be further supported by the phosphonate oxygens
during the deprotonation process. The stepwise pK value of the
[CuH4L2]2ꢁ ? [CuH3L2]3ꢁ + H+ reaction is only slightly lower than
the respective deprotonation of the free ligand (pK = 4.67 versus
5.00). The presence of two phosphonate units in each ligand mol-
ecule and their negative charge strongly favors complex proton-
ation; the pK values of further deprotonation reactions are higher
than the respective constants in the free ligand (Table 2). Moreover
it decreases the stability of 1:2 complexes in comparison to 1:1
species.
NMR spectra were measured on a Bruker Avance TM DRX
300 MHz spectrometer in D2O with additive of NaOD or anhydrous
Na2CO3 solutions, using 300.13 MHz for 1H NMR, 121.51 MHz for
31P NMR and 75.48 MHz for 13C NMR spectra, respectively 31P
NMR spectra were recorded with proton decoupling (31P{1H}NMR)
and without decoupling (31P NMR), in order to determine the shift
of two phosphorus atoms. Melting points were determined using
an Electrothermal 9200 apparatus and a Boetius hot-stage appara-
tus and were uncorrected. Reagents used were obtained from the
´
Sigma–Aldrich Company (Poznan, Poland). Solvents were of com-
mercial quality and purchased from a local supplier (POCh Gliwice,
Poland).
For other 2-Py derivatives studied in this paper, e.g. L4 and L7, no
formation of bis complexes was observed. Introduction of methyl
group or bulky phenyl ring constitutes sterical hindrance which to-
gether with a charge repulsion coming from the second phospho-
nate group prevents formation of these species.
4.2. Synthesis
Preparation of starting diethyl 1-aminomethylphosphonate
1a–c: diethyl aminomethylphosphonate (1a) was prepared by a
literature procedure [24]. Diethyl 1-amino-1-phenylmethyl-phos-
phonate (1b) was prepared as described in a literature [25]:
Diethyl N-benzylidene-1-phenyl-1-aminomethylphosphonate
[12b] (25.0 g, 0.075 mol) was dissolved in diethyl ether (60 mL),
cooled and a mixture of concentrated hydrochloric acid (8 mL),
diethyl ether (30 mL) and methanol (20 mL) was gradually added.
The mixture was refrigerated for 1 h and the precipitated product
was collected by filtration, washed with diethyl ether (2 ꢃ 50 mL)
to give the pure diethyl 1-amino-1-phenylmethylphosphonate
hydrochloride (16 g, 76%): 31P{1H} NMR (121 MHz, D2O, 25 °C):
d = 18.6 (s) ppm. 1H NMR (300 MHz, D2O, 25 °C): d = 1.1 (t,
J = 7.0 Hz, 3H, CH3), 1.2 (t, J = 7.0 Hz, 3H, CH3), 4.0–4.1 (m, 4H,
CH2O), 4.8 (d, J = 17.8 Hz, 1H, CHP), 7.4 (m, 5H, Ph) ppm.
In order to discuss the stability of the studied Cu(II) complexes
in comparison to complexes of other ligands we propose to use the
pCu(II) value (Table 5), calculated at pH 7.4 for [L] = 10ꢁ5 M and
[Cu(II)] = 10ꢁ6 M, which eliminates the differences in ligand pro-
tonation constants [23]. The pCu(II) values presented in Table 5
show that under these conditions the ligands presented in this pa-
per have similar affinities for Cu(II) and all of them appear to be a
better complexing agents than previously designed iminobisphos-
phonic ligands substituted at the secondary amino moiety [3c].
Even though the substitution of the hydrogen by aliphatic or aro-
matic groups on carbon chain or secondary amino group changes
the binding ability, this effect is due only to changes of protonation
constants. In this series the pyridine moiety is not participating in
copper binding and the coordination pattern reminds the same.
Comparison of the pCu(II) values of ligand L9 with its amin-
omonophosphonate precursor L8 studied earlier [19b], shows that
introduction of two phosphonic functions into one molecule dra-
matically improves its binding ability towards copper ion (Table
Diethyl 1-methyl-1-aminoethylphosphonate (1c) was prepared
by modified literature procedure [26]: ammonia was bubbled
through a cooled acetone (46.4 g, 0.80 mol) solution of diethyl
phosphonate (77.4 mL, 0.60 mol) for 60 min. Then the ammonia
was stopped and the mixture was heated to boiling point and kept

W. Goldeman et al. / Inorganica Chimica Acta 365 (2011) 391–399
397
for 60 min. The reaction mixture was then cooled to room temper-
ature and diethyl ether was added (150 mL) with stirring. The
diethyl ether layer was separated, dried and evaporated to dryness
to give an oily residue, which was distilled under reduced pressure
and oily fraction 63–83 °C/1 mmHg was collected (52 g). It was a
mixture of diethyl 1-methyl-1-aminoethylphosphonate and
diethyl phosphonate with 43:57 a molar ratio. The oil was dis-
solved in acetone (150 mL) and solution of oxalic acid (19 g) in ace-
tone (50 mL) was added. The mixture was refrigerated overnight
and the separated product was collected by filtration, washed with
cold acetone (3 ꢃ 50 mL) to give pure diethyl 1-methyl-1-amin-
oethylphosphonate oxalate (42.1 g, yield 25% based on starting
diethyl phosphonate): 31P{1H} NMR (121 MHz, D2O, 25 °C):
d = 24.4 (s) ppm. 1H NMR (300 MHz, D2O, 25 °C): d = 1.1 (t,
J = 7.0 Hz, 6H, CH3CH2), 1.3 (d, J = 15.5 Hz, 6H, 2xCH3), 4.1 (q,
J = 7.0 Hz, 4H, OCH2) ppm.
J = 3.0, J = 13.2, CH2P) ppm. 1H NMR (300 MHz, D2O + NaOD, 25 °C):
d = 2.1 (dd, J = 13.2, J = 13.2, 1H, CH2P), 2.3 (dd, J = 13.1, J = 13.1, 1H,
CH2P), 3.6 (d, J = 18.9, 1H, CHP), 7.3 (d, J = 4.6, 2H, 2-, 6-Py), 8.2 (d,
J = 4.6, 2H, 3-, 5-Py) ppm. 13C NMR (75 MHz, D2O + NaOD, 25 °C):
d = 47.3 (dd, J = 137.6, J = 13.3, CH2P), 65.5 (dd, J = 123.5, J = 7.2,
CHP), 124.1 (d, J = 3.5, 2-, 6-Py), 147.9 (s, 3-, 5-Py), 151.7 (s, 1-Py)
*
ppm. Elemental Anal. Calc. for C7H12N2O6P2 H2O: C, 28.01; H, 4.70;
N, 9.33. Found: C, 27.40; H, 4.67; N, 8.95.
N-(1-methyl-1-phosphonoethyl)-1-amino-1-(2-pyridyl)-methyl-
phosphonic acid (5d): 31P{1H} NMR (121 MHz, D2O + NaOD, 25 °C):
d = 17.5 (s, PyCP), 25.1 (s, Me2CP) ppm. 31P NMR (121 MHz,
D2O + NaOD, 25 °C): d = 17.5 (d, PyCP, J = 21.2), 25.1 (qq, Me2CP,
J = 13.6) ppm. 1H NMR (300 MHz, D2O + NaOD, 25 °C): d = 0.4 (d,
J = 14.0, 3H, CH3), 1.1 (d, J = 13.5, 3H, CH3), 4.0 (d, J = 21.2, 1H,
CHP), 7.0 (t, J = 5.2, 1H, 4-Py), 7.4 (d, J = 7.6, 1H, 6-Py), 7.5 (t, J = 7.6,
1H, 5-Py), 8.2 (d, J = 5.2, 1H, 3-Py) ppm. 13C NMR (75 MHz,
D2O + NaOD, 25 °C): d = 21.3 (s, CH3), 23.5 (s, CH3), 54.4 (dd,
J = 148.0, J = 11.7, Me2CP), 58.6 (dd, J = 128.4, J = 12.9, PyCP), 121.3
(d, J = 2.2), 123.9 (d, J = 3.6), 136.7 (d, J = 1.9), 147.5 (s), 163.5 (d,
The free bases 1b and 1c were liberated from its hydrochloride
and oxalate by treatment of these salts with an excess of aqueous
sodium bicarbonate, and extracted with CH2Cl2. The extract was
dried and evaporated, giving the 1b and 1c, as oils.
*
J = 3.8, 1-Py) ppm. Elemental Anal. Calc. for C9H16N2O6P2 H2O: C,
General procedure for preparation of iminobisphosphonic acids
5: To a cooled solution of appropriate dialkyl 1-aminophosphonate
(10 mmol) in dichloromethane (30 mL), pyridine aldehyde (1.07 g,
10 mmol) was added and the mixture was stirred for 1 h. Then
anhydrous sodium sulfate (5 g) was added and the mixture was left
for 24 h at room temperature. After this, sodium sulfate was fil-
tered off and the reaction mixture was cooled in water-ice bath,
and triethyl phosphite was added (1.66 g, 10 mmol), followed by
trimethylsilyl bromide (TMSBr, 9.2 mL, 70 mmol). The reaction
mixture was allowed to warm to room temperature and kept over-
night, protected against moisture. Then the mixture was evapo-
rated to dryness, the oily residue was dissolved in diethyl ether
(25 mL) and methanol (10 mL) was added with cooling. After sev-
eral hours of cooling, the product has precipitated, which was col-
lected by filtration, dried and recrystallized from water or water/
acetone solution. Yields and m.p.’s of the iminobisphosphonic acids
5 are given in Table 1.
N-(phosphonomethyl)-1-amino-1-(2-pyridyl)-methylphosphon-
ic acid (5a): 31P{1H}NMR (121 MHz, D2O + NaOD, 25 °C): d = 15.6 (d,
J = 4.0, PyCP), 18.0 (d, J = 4.0, CH2P) ppm. 31P NMR (121 MHz,
D2O + NaOD, 25 °C): d = 15.9 (dd, J = 4.0, J = 17.8, PyCP), 18.0 (dt,
J = 4.0, J = 13.1, CH2P) ppm. 1H NMR (300 MHz, D2O + NaOD, 25 °C):
d = 2.2 (d, J = 13.2, 2H, CH2P), 3.6 (d, J = 17.8, 1H, CHP), 7.1 (t, J = 5.4,
1H, 4-Py), 7.3 (d, J = 7.8, 1H, 6-Py), 7.6 (dt, J = 1.5, J = 7.8, 1H, 5-Py),
8.2 (d, J = 5.4, 1H, 3-Py) ppm. 13C NMR (75 MHz, D2O + NaOD,
25 °C): d = 47.8 (dd, J = 13.1, J = 138.5, CH2P), 67.6 (dd, J = 14.5,
J = 128.9, CHP), 121.8 (s), 123.7 (s), 137.1 (s), 147.9 (s), 160.0 (s)
32.94; H, 5.53; N, 8.54. Found: C, 32.45; H, 5.48; N, 8.32%.
N-(1-methyl-1-phosphonoethyl)-1-amino-1-(3-pyridyl)-methyl-
phosphonic acid (5e): 31P{1H}NMR (121 MHz, D2O + NaOD, 25 °C):
d = 18.0 (s, PyCP), 25.1 (s, Me2CP) ppm. 31P NMR (121 MHz,
D2O + NaOD, 25 °C): d = 18.0 (d, J = 21.0, PyCP), 25.1 (qq, J = 13.6,
Me2CP) ppm. 1H NMR (300 MHz, D2O + NaOD, 25 °C): d = 0.5 (d,
J = 13.9, 3H, CH3), 1.0 (d, J = 13.6, 3H, CH3), 3.9 (d, J = 21.1, 1H,
CHP), 7.2 (dd, J = 4.9, J = 7.8, 1H, 5-Py), 7.8 (d, J = 7.8, 1H, 6-Py), 8.1
(d, J = 4.9, 1H, 4-Py), 8.4 (s, 1H, 2-Py) ppm. 13C NMR (75 MHz,
D2O + NaOD, 25 °C): d = 21.7 (s, CH3), 25.1 (s, CH3), 54.6 (dd,
J = 147.0, J = 12.5, Me2CP), 55.1 (dd, J = 133.0, J = 12.0, PyCP), 123.4
(s), 137.4 (d, J = 4.4), 141.3 (d, J = 3.6, 1-Py), 145.6 (d, J = 1.7), 148.8
(d, J = 3.0) ppm. Elemental Anal. Calc. for C9H16N2O6P2*H2O: C,
32.94; H, 5.53; N, 8.54. Found: C, 33.60; H, 5.41; N, 8.03%.
N-(1-methyl-1-phosphonoethyl)-1-amino-1-(4-pyridyl)-methyl-
phosphonic acid (5f): 31P{1H} NMR (121 MHz, D2O + NaOD, 25 °C):
d = 17.1 (s, PyCP), 25.1 (s, Me2CP) ppm. 31P NMR (121 MHz,
D2O + NaOD, 25 °C): d = 17.1 (d, J = 21.9, PyCP), 25.1 (qq, J = 13.7,
Me2CP) ppm. 1H NMR (300 MHz, D2O + NaOD, 25 °C): d = 0.6 (d,
J = 13.9, 3H, CH3), 1.0 (d, J = 13.5, 3H, CH3), 3.9 (d, J = 21.8, 1H,
CHP), 7.5 (d, J = 5.0, 2H, 2-, 6-Py), 8.2 (d, J = 5.0, 2H, 3-, 5-Py) ppm.
13C NMR (75 MHz, D2O + NaOD, 25 °C): d = 21.6 (s, CH3), 24.8 (s,
CH3), 54.8 (dd, J = 149.6, J = 12.2, Me2CP), 57.2 (dd, J = 128.3,
J = 12.0, PyCP), 124.5 (s, 2-, 6-Py), 147.4 (s, 3-, 5-Py), 156.8 (d,
J = 3.2, 1-Py) ppm. Elemental Anal. Calc. for C9H16N2O6P2*H2O: C,
32.94; H, 5.53; N, 8.54. Found: C, 30.94; H, 5.32; N, 7.98%.
Diastereoisomeric mixture of N-(1-phenylphosphonomethyl)-
1-amino-1-(2-pyridyl)-methylphosphonic acid (5g): 31P{1H} NMR
(121 MHz, D2O + Na2CO3, 25 °C): d = major diastereoisomer 15.8
(s, PyCP, 73%), 17.2 (s, PhCP, 73%) ppm, minor diastereoizomer
15.4 (s, PyCP, 27%), 16.4 (s, PhCP, 27%) ppm. 1H NMR (121 MHz,
D2O + Na2CO3, 25 °C): d = major diastereoisomer: 3.3 (d, J = 18.0,
1H, PhCHP), 3.5 (d, J = 17.7, 1H, PyCHP), 6.9–7.2 (m, 7H, Ph+4-, 6-
Py), 7.6 (t, J = 7.5, 1H, 5-Py), 8.2 (t, J = 7.4, 1H, 3-Py) ppm, minor
diastereoisomer: 3.7 (d, J = 17.6, 1H, PhCHP), 3.7 (d, J = 18.2, 1H,
PyCHP), 6.9–7.2 (m, 7H, Ph+4-, 6-Py), 7.2 (t, J = 7.5, 1H, 5-Py), 7.9
(d, J = 4.6, 1H, 3-Py) ppm. 13C NMR (121 MHz, D2O + Na2CO3,
25 °C): d = major diastereoisomer: 60.5 (dd, J = 12.5, J = 83.5, CP),
61.8 (dd, J = 12.6, J = 76.9, CP), 121.8 (s), 124.3 (d, J = 3.2), 126.4
(s), 128.0 (s), 128.9 (d, J = 4.8), 137.1 (s), 139.2 (d, J = 2.9), 148.0
(s), 158.6 (d, J = 5.0), 164.2 (Na2CO3) ppm, minor diastereoisomer:
66.2 (dd, J = 11.0, J = 45.0, CP), 67.9 (dd, J = 10.6, J = 39.0, CP), 121.5
(s), 124.2 (d, J = 2.8), 125.8 (s), 127.2 (s), 129.2 (d, J = 5.2), 136.5 (s),
139.9 (d, J = 4.1), 146.5 (s), 159.9 (d, J = 4.1), 164.2 (Na2CO3) ppm.
*
ppm. Elemental Anal. Calc. for C7H12N2O6P2 H2O: C, 28.01; H, 4.70;
N, 9.33. Found: C, 27.75; H, 4.69; N, 9.08%.
N-(phosphonomethyl)-1-amino-1-(3-pyridyl)-methylphosphon-
ic acid (5b): 31P{1H}NMR (121 MHz, D2O + NaOD, 25 °C): d = 15.9 (d,
J = 3.6, PyCP), 18.0 (d, J = 3.6, CH2P) ppm. 31P NMR (121 MHz,
D2O + NaOD, 25 °C): d = 15.9 (dd, J = 3.6, J = 19.8, PyCP), 18.0 (dt,
J = 3.6, J = 13.2, CH2P) ppm. 1H NMR (300 MHz, D2O + NaOD, 25 °C):
d = 2.1 (dd, J = 13.2, J = 13.2, 1H, CH2P), 2.3 (dd, J = 13.2, J = 13.2, 1H,
CH2P), 3.6 (d, J = 17.7, 1H, CHP), 7.2 (dd, J = 4.9, J = 7.5, 1H, 5-Py),
7.7 (d, J = 7.5, 1H, 6-Py), 8.2 (d, J = 4.9, 1H, 4-Py), 8.3 (s, 1H, 2-Py)
ppm. 13C NMR (75 MHz, D2O + NaOD, 25 °C): d = 45.9 (dd, J = 128.2,
J = 6.2, CH2P), 62.2 (dd, J = 123.5, J = 7.2, CHP), 124.2 (s), 131.4 (s),
137.4 (d, J = 3.6), 148.1 (s), 149.1 (d, J = 5.2) ppm. Elemental Anal.
*
Calc. for C7H12N2O6P2 H2O: C, 28.01; H, 4.70; N, 9.33. Found: C,
29.05; H, 4.24; N, 9.45%.
N-(phosphonomethyl)-1-amino-1-(4-pyridyl)-methylphosphon-
ic acid (5c): 31P{1H}NMR (121 MHz, D2O + NaOD, 25 °C): d = 15.0 (d,
J = 3.0, PyCP), 18.0 (d, J = 3.3, CH2P) ppm. 31P NMR (121 MHz,
D2O + NaOD, 25 °C): d = 15.0 (dd, J = 3.0, J = 19.6, PyCP), 18.0 (dt,
*
Elemental Anal. Calc. for C13H16N2O6P2 H2O: C, 41.50; H, 4.82; N,
7.45. Found: C, 41.35; H, 4.74; N, 7.35.

398
W. Goldeman et al. / Inorganica Chimica Acta 365 (2011) 391–399
Single diastereoisomer of N-(1-phenylphosphonomethyl)-1-
was judged by the values of the sample standard deviation, S, and
the goodness of fit, E = 0.1 mV (0.0023 rpH
2, (Pearson’s test). At
and
V = 0.003 mL, the values of S is given in Table 2, and v2 was
amino-1-(3-pyridyl)-methylphosphonic acid (5h): 31P{1H}NMR
(121 MHz, D2O + NaOD, 25 °C): d = 17.1 (d, J = 1.5, PyCP), 17.9 (d,
J = 1.5, PhCP) ppm. 1H NMR (300 MHz, D2O + NaOD, 25 °C):
d = 3.6 (d, J = 18.0, 1H, PhCHP), 3.7 (d, J = 17.3, 1H, PyCHP), 7.1 (d,
J = 6.4, 2H, o-ArH), 7.2 (m, 3H, m + p-ArH), 7.4 (dd, J = 5.0, J = 7.4,
1H, 5-Py), 7.8 (d, J = 7.4, 1H, 6-Py), 8.1 (s, 1H, 2-Py), 8.3 (d, J = 5.0,
1H, 4-Py) ppm. 13C NMR (75 MHz, D2O + NaOD, 25 °C): d = 57.6
(dd, J = 10.8, J = 129.8, PyCP), 59.9 (dd, J = 10.2, J = 134.2, PhCP),
124.6 (s), 127.8 (s), 128.7 (s), 128.7 (s), 132.9 (s), 134.7 (d,
J = 3.2), 139.0 (s), 146.2 (s) 147.44 (s) ppm. Elemental Anal. Calc.
for C13H16N2O6P2*H2O: C, 41.50; H, 4.82; N, 7.45. Found: C,
42.20; H, 4.37; N, 7.44%.
v
r
)
r
below 12.6. The scatter of residuals versus pH was reasonably ran-
dom, without any significant systematic trends, thus indicating a
good fit of the experimental data. The successive protonation con-
stants were calculated from the cumulative constants determined
with the program. The uncertainties in the log K values correspond
to the added standard deviations in the cumulative constants. The
distribution curves of the protonated species of L as a function of
pH were calculated using the HYSS2006 program.[29]
Additionally, a combined potentiometric and UV–Vis titrations
were carried out. Absorption spectra (190–400 nm) were recorded
using a Varian CARY 50 (Varian) probe UV–Vis spectrophotometer
fitted with Varian optical fibers (Technologies, Inc., 908.707.1009,
Stainless Steel) and immersion probe made of quartz suprazil
(Varian, Technologies Inc.973.984.9092, 5 mm path Replaceable
S. Steel Tip).
The initial pH of 20 mL ligands samples was adjusted to be
acidic or basic, and the titration of the solution was then carried
out by addition of known volumes of NaOH or HClO4, respectively,
dosed by the Titrando 809 titrator. The spectrophotometric data
were analysed with SPECFIT [18a–c,30] program which adjust the
absorptivities and the stability constants of the species formed at
equilibrium. Specfit uses factor analysis to reduce the absorbance
matrix and to extract the eigenvalues prior to the multiwavelength
fit of the reduced data set according to the Marquardt algorithm
[18d,e].
To probe the coordination properties of the new ligands with
Cu(II), a UV–Vis spectrophotometric titrations in the range of d–d
bands (400–800 nm) were recorded on a Varian CARY 300 spectro-
photometer in a Hellma quartz optical cell (1 cm). Electron para-
magnetic resonance spectra were collected on a Bruker ESP 300E
spectrometer at X-band frequency (9.4 GHz) at 120 K.
Diastereoisomeric mixture of N-(1-phenylphosphonomethyl)-
1-amino-1-(4-pyridyl)-methylphosphonic acid (5i): 31P{1H}NMR
(121 MHz, D2O, 25 °C): d = major diastereoisomer 9.9 (s, PyCP,
61%), 14.6 (s, PhCP, 61%), minor diastereoizomer 8.4 (s, PyCP,
39%), 12.3 (s, PhCP, 39%) ppm. 1H NMR (300 MHz, D2O, 25 °C):
d = major diastereoisomer: 3.9 (d, J = 18.8, 1H, PhCHP), 4.2 (d,
J = 19.2, 1H, PyCHP), 7.1 (m, 2H, o-ArH), 7.2 (m, 3H, p- + m-ArH),
7.8 (d, 2H, J = 5.4, 2-, 6-Py,), 8.5 (d, J = 5.4, 2H, 3-, 5-Py) ppm, minor
diastereoisomer: 4.4 (d, J = 17.0, 1H, PhCHP), 4.5 (d, J = 18.0, 1H,
PyCHP), 7.1 (m, 2H, o-ArH), 7.2 (m, 3H, p- + m-ArH), 7.7 (d,
J = 6.0, 2H, 2-, 6-Py), 8.4 (d, J = 6.0, 2H, 3-, 5-Py) ppm. 13C NMR
(75 MHz, D2O + Na2CO3, 25 °C): d = major diastereoisomer: 59.4
(dd, J = 12.1, J = 12.1, CP), 61.1 (dd, J = 13.6, J = 17.2, CP), 124.6 (d,
J = 3.5), 126.2 (s), 127.9 (s), 129.0 (d, J = 4.8), 139.0 (d, J = 3.7),
147.8 (s), 151.5 (d, J = 4.2), 162.9 (Na2CO3) ppm, minor diastereo-
isomer: 65.4 (dd, J = 12.1, J = 42.4, CP), 67.2 (dd, J = 12.1, J = 48.1,
CP), 124.8 (d, J = 4.3), 125.9 (s), 127.2 (s), 129.5 (d, J = 5.4), 141.0
(d, J = 3.8), 146.9 (s), 153.1 (d, J = 3.6), 162.9 (Na2CO3) ppm. Ele-
*
mental Anal. Calc. for C13H16N2O6P2 H2O: C, 41.50; H, 4.82; N,
7.45. Found: C, 40.78; H, 4.80; N, 6.67.
4.3. Materials and physico-chemical measurements
The metal ion concentration was 2 ꢃ 10ꢁ3 M and metal-to-
ligand molar ratio varied from 1:1 to 1:5. EPR spectra were
performed in the ethylene glycol–water (1:2 v/v) solution. The
spectroscopic parameters were obtained at the maximum concen-
tration of the particular species as indicated by the potentiometric
calculations.
Starting materials and solvents. The solution studies were carried
out in bidistilled water. All the chemicals were commercial prod-
ucts of reagent grade and were used without further purification.
Copper(II) solutions were prepared from Cu(ClO4)2ꢄ6H2O (Aldrich).
Potentiometric titrations. The potentiometric titrations were per-
formed using an automatic titrator system Titrando 809 (Metr-
ohm) with a combined glass electrode (Mettler Toledo InLab
Semi-Micro) filled with 3 M KCl (Mettler Toledo) in water. The
electrode was calibrated daily in hydrogen ion concentration using
HClO4 (Applichem) [27]. Carbonate-free NaOH solution (0.1 M Al-
drich) was standardized by titration with potassium hydrogen
phthalate (Fluka, puriss. p.a.). The ionic strength was fixed at
I = 0.1 M with NaClO4 (Fluka, puriss. p.a.). The experiments were
carried out at constant temperature of 25 0.2 °C. A stream of ar-
gon, pre-saturated with water vapour, was passed over the surface
of the solution. The ionic product of water for these conditions was
10ꢁ13,77 mol2 dmꢁ6. All the titrations were carried out on a 3 mL
samples. Metal–ligand system titrations were performed on solu-
tions of ligand concentrations of 2 – 4.2 ꢃ 10ꢁ3 M and copper(II)-
to-ligand molar ratios of 1:1, 1:2, 1:3 and 1:5.
Acknowledgments
The authors thank Professor Henryk Kozlowski (University of
Wroclaw) for helpful discussions. This research was supported by
an internal grant from the Faculty of Chemistry W-3, Wroclaw
University of Technology. E.G.-K. thanks the Polish Ministry of
Science and Higher Education for the grant N N204 308137.
References
[1] M.I. Kabachnik, T.Ya. Medved, N.M. Dyatlova, M.V. Rudomino, Russ. Chem. Rev.
43 (1974) 733.
[2] (a) Candau, D.; Collin, N.; Quemin, E. US Patent 6010706 (1997);
(b) Perkins P. G. European Patent 0353973 1989;
(c) Suzuki F. US Patent 4176059 (1978);
(d) Howell, J. K., Jr. US Patent 4180603 (1977);
(e) Kowalski, X. US Patent 3671448 (1972).
[3] (a) E. Matczak-Jon, B. Kurzak, A. Kamecka, W. Sawka-Dobrowolska, P. Kafarski,
J. Chem. Soc., Dalton. Trans. 20 (1999) 3627;
The potentiometric data (about 140 points collected over the pH
range 2.2–11.4) were refined with the SUPERQUAD [28a] program
which uses non-linear least-squares methods [28b]. Potentiomet-
ric data points were weighted by a formula allowing greater
pH errors in the region of an end-point than elsewhere. The
weighting factor Wi is defined as the reciprocal of the estimated
(b) R.R. Carter, R.L. Carroll, R.R. Irani, Inorg. Chem. 6 (5) (1967) 939;
(c) B. Kurzak, A. Kamecka, K. Kurzak, J. Jezierska, P. Kafarski, Polyhedron 17
(1998) 4403;
(d) B. Kurzak, A. Kamecka, K. Kurzak, J. Jezierska, P. Kafarski, Polyhedron 19
(2000) 2083.
variance of measurements: Wi ¼ 1=r2i ¼ 1=½rE2 þ ðdE=dVÞ2r2V
]
[4] (a) Z. Chuanfang, X. Haiyan, G. Xinlei, Cailiao Baohu, 31 (7) (1998) 3. (Chem.
Abstr. 130 (1999) 128247);
where r2E and r2V are the estimated variances of the potential and
volume readings, respectively. The constants were refined by min-
imising the error-square sum, U, of the potentials. The quality of fit
(b) R.R. Irani, K. Moedritzer, US Patent 3344077, (1967);
(c) R.R. Irani, K. Moedritzer, US Patent 3269812, (1966);
(d) R.R. Irani, K. Moedritzer, US Patent 3257479, (1966);

W. Goldeman et al. / Inorganica Chimica Acta 365 (2011) 391–399
399
(e) P.C. Hamm, US Patent 3556762, (1971);
(f) The Merck Index, 12th ed., vol. 4522, Merck & Co., Inc., 1996, p. 768.
[5] (a) B. Boduszek, Tetrahedron 52 (1996) 12483;
[15] (a) A. Dehnel, J.P. Finet, G. Lavielle, Synthesis (1977) 474;
(b) G.A. Russell, C.-F. Yao, J. Org. Chem. 57 (1992) 6508;
(c) A. Heymes, I. Chekroun, Synthesis (1987) 245;
(b) B. Boduszek, R. Latajka, W. Les´niak, Phosphorus Sulfur Silicon 165 (2000)
53;
(c) B. Boduszek, Synth. Commun. 33 (2003) 4087;
(d) W. Goldeman, T.K. Olszewski, B. Boduszek, W. Sawka-Dobrowolska,
Tetrahedron 62 (2006) 4506;
(d) D.M. Malenko, L.I. Nesterova, S.N. Lukyanenko, A.D. Sinitsa, Zh. Obshch.
Khim. 60 (1990) 1186 (Chem. Abstr. 113 (1990) 172208);
(e) P.P. Onysko, T.V. Kim, E.I. Kiseleva, A.D. Sinitsa, Zh. Obshch. Khim. 66 (8)
(1996) 1283 (Chem. Abstr. 126 (1997) 89474);
(f) P.P. Onysko, T.V. Kim, E.I. Kiseleva, A.D. Sinitsa, Zh. Obshch. Khim. 63 (8)
(1993) 1906 (Chem. Abstr. 120 (1994) 245326);
(e) W. Goldeman, B. Boduszek, Phosphorus Sulfur Silicon 184 (2009) 1413.
[6] K.A. Petrov, F.L. Maklyaev, N.K. Bliznyuk, Zh. Obshch. Khim. 29 (1959) 591
(Chem. Abstr. 54 (1960) 1625).
(g) P.P. Onysko, T.V. Kim, E.I. Kiseleva, A.D. Sinitsa, Russ. J. Gen. Chem. 67 (10)
(1997) 1544;
[7] (a) N.V. Tsirul’nikova, N.P. Demina, D.G. Danielyan, I.V. Karandeeva, V.Ya.
Temkina, Zh. Obshch. Khim. 60 (4) (1990) 734 (Chem. Abstr. 113 (1990)
78539);
(h) P.P. Onysko, T.V. Kim, E.I. Kiseleva, A.V. Turov, Zh. Obshch. Khim. 60 (6)
(1990) 1425 (Chem. Abstr.114 (1991) 6326).
[16] (a) H.A. Dondas, Y. Durust, R. Grigg, M.J. Slater, M.A.B. Sarker, Tetrahedron 61
(45) (2005) 10667;
(b) T.R. Varga, Synth. Commun. 27 (17) (1997) 2899;
(c) D. Sanna, I. Bodi, S. Bouhsina, G. Micera, T. Kiss, J. Chem. Soc., Dalton Trans.
18 (1999) 3275;
(b) A. Dehnel, J.M. Kanabus-Kaminska, G. Lavielle, Can. J. Chem. 66 (1988) 310;
(c) A. Heymes, I. Chekroun, Synthesis 3 (1987) 245;
(d) A.G. Matveeva, M.P. Pasechnik, P.V. Petrovsky, S.V. Matveev, S.A. Pisareva,
Russ. Chem. Bull. 49 (6) (2000) 1045.
(d) P.P. Onysko, T.V. Kim, E.I. Kiseleva, A.D. Sinitsa, Zh. Obshch. Khim. 66 (6)
(1996) 936 (Chem. Abstr. 125 (1996) 328899);
[8] (a) K. Moedritzer, R.R. Irani, J. Org. Chem. 31 (1966) 1603;
(b) R.R. Irani, K. Moedritzer, US Patent 3257479, (1962) (Chem. Abstr. 65
(1966) 13761c).
(e) P.P. Onysko, T.V. Kim, Yu.V. Rassukanaya, E.I. Kiseleva, A.D. Sinitsa, Russ. J.
Gen. Chem. 74 (9) (2004) 1341.
[17] B. Boduszek, Polish J. Chem. 75 (2001) 663.
[9] (a) D. Redmore, B. Dhawan, Phosphorus Sulfur 16 (1983) 233;
(b) B. Dhawan, D. Redmore, D. Phosphorus, Sulfur Silicon Relat. Elem. 48 (1990)
41;
[18] (a) H. Gampp, M. Maeder, C.J. Meyer, A.D. Zuberbühler, Talanta 32 (1985) 95;
(b) H. Gampp, M. Maeder, C.J. Meyer, A.D. Zuberbühler, Talanta 32 (1985) 257;
(c) H. Gampp, M. Maeder, C.J. Meyer, A.D. Zuberbühler, Talanta 33 (1986) 943;
(d) D.W. Marquardt, J. Soc. Ind. Appl. Math. 11 (1963) 431;
(e) M. Maeder, A.D. Zuberbühler, Anal. Chem. 62 (1990) 2220.
[19] (a) L. Chrus´cin´ ski, P. Młynarz, K. Malinowska, J. Ochocki, B. Boduszek, H.
Kozłowski, Inorg. Chim. Acta 303 (2000) 47;
(c) V.-M. Mukkala, M. Kwiatkowski, J. Kankare, H. Takalo, Helv. Chim. Acta 76
(2) (1993) 893;
(d) G.L. Matevosyan, P.M. Zavlin, Russ. J. Gen. Chem. 68 (9) (1998) 1467;
(e) J.-L. Song, J.-G. Mao, Y.-Q. Sun, A. Clearfield, Eur. J. Inorg. Chem. 23 (2003)
4218;
(b) R. Lipin´ ski, L. Chrus´cin´ ski, P. Młynarz, B. Boduszek, H. Kozłowski, Inorg.
(f) S.-M. Ying, J.-G. Mao, Eur. J. Inorg. Chem. 6 (2004) 1270.
[10] (a) E. Uhlig, W. Achilles, J. Prakt. Chem. 311 (1969) 529;
(b) S. Westerback, K.S. Rajan, A.E. Martell, J. Am. Chem. Soc. 87 (1965) 2567;
(c) F.C. Bersworth, US Patent 2599807, 1952 (Chem. Abstr. 47 (1953) 4360b).;
(d) G. Schwarzenbach, H. Ackermann, P. Ruckstuhl, Helv. Chim. Acta 32 (1949)
1175.
[11] (a) Zh.M. Ivanova, T.V. Kim, E.A. Suvalova, I.E. Boldeskul, Yu.G. Gololobov, Zh.
Obshch. Khim. 46 (2) (1976) 236 (Chem. Abstr. 85 (1976) 21540);
(b) K. Issleib, Kl.-P. Dopfer, A.Z. Balszuweit, Anorg. Allg. Chem. 444 (1978) 249.
[12] (a) M. Soroka, K. Kołodziejczyk, Polish Patent 187457, 2004 (Chem. Abstr. 144
(2007) 51712);
Chim. Acta 322 (2001) 157.
[20] J. Galezowska, P. Kafarski, H. Kozłowski, P. Młynarz, V.M. Nurchi, T. Pivetta,
Inorg. Chim. Acta 362 (2009) 707.
_
[21] M. Dyba, M. Jezowska-Bojczuk, T. Kiss, E. Kiss, H. Kozłowski, Y. Leroux, D. El
Manouni, J. Chem. Soc., Dalton Trans. (1996) 1119.
[22] T.G. Fawcett, E.E. Bernarducci, K. Krogh-Jespersen, H.J. Schugar, J. Am. Chem.
Soc. 102 (1980) 2598.
[23] W.R. Harris, C.J. Carrano, K.N. Raymond, J. Am. Chem. Soc. 101 (1979) 2213.
[24] K.D. Steven, W.P. Gerald, F.M. Stephen, Org. Syntheses (1993). Coll. 8, 451.
[25] K. Kołodziejczyk, M.S. Thesis, Wroclaw University of Technology, 2001.
[26] K.A. Petrov, V.A. Chauzov, L.V. Pastukhova, N.N. Bogdanov, Zh. Obshch. Khim.
46 (1976) 1246 (Chem. Abstr. 85 (1976) 94451).
(b) M. Soroka, K. Kołodziejczyk, Tetrahedron Lett. 44 (2003) 1863;
(c) M. Soroka, K. Kołodziejczyk, Polish Patent, 2004, 188415 (Chem. Abstr. 144
(2006) 51714).
[27] P. Gans, B. O’Sullivan, Talanta 51 (2000) 33.
[28] (a) P. Gans, A. Sabatini, A. Vacca, J. Chem. Soc., Dalton Trans. (1985) 1195;
[13] (a) M.N. Dimukhametov, R.Z. Musin, B.I. Buzykin, S.K. Latypov, V.F. Mironov,
Mendeleev Commun. (2005) 40;
(b) P. Gans, Data Fitting in the Chemical Sciences, John Wiley
Chichester, 1992.
& Sons,
(b) E.V. Bayandina, E.Yu. Davydova, M.A. Abaskalova, R.Z. Musina, V.A.
Alfonsov, Russ. Chem. Bull Int. Ed. 54 (6) (2005) 1492.
[14] I. van Assche, M. Soroka, A. Haemers, M. Hooper, D. Blanot, J. van Heijenoort,
Eur. J. Med. Chem. Chim. Ther. 26 (5) (1991) 505.
[29] L. Alderighi, P. Gans, A. Ienco, D. Peters, A. Sabatini, A. Vacca, Coord. Chem. Rev.
(1999) 311.
[30] F.J.C. Rossotti, H.S. Rossotti, R.J. Whewell, J. Inorg. Nucl. Chem. 33 (1971) 2051.