and extracted with Et2O (2 × 100 cm3). The combined organic
extracts where washed with water and dried over MgSO4. The
solution was filtered and the solvent was removed in vacuo.
Aminonitriles 11 were obtained in nearly quantitative yields
as highly unstable oils and were hydrolysed immediately after
Determination of the purity of chelating agents
The details of the method employed to determine the titrimetric
purity of the free chelating agents, using spectrophotometric
titration with Fe(III) has been described in an earlier paper.6 The
free ligands were previously dissolved in a volume of 0.200 M
NaOH calculated to be four times the molar amount of the
ligand. The pH was fixed at 6 by the addition of 2 mM MES
buffer [2-(N-morpholino)ethanesulfonic acid]. The experimental
solution (60 cm3) was placed in a 150 cm3 thermostated jacketed
reaction vessel provided with airtight cap fitted with a gas inlet
and outlet tubes, combined pH glass electrode, white-light
spectrode, two piston burettes (tips placed below the surface
of the solution) and magnetic stirrer. The photometric titra-
tion consists on the addition of 4.47 × 10−4 M Fe(III) standard
solution to the chelating agent (samples of about 1 × 10−4 M)
until the absorbance at 480 nm presented no changes. Molar
absorptivities were also calculated at 480 nm for each chelating
agent (see Table 1S in ESI†). The photometric curves, used to
calculate the end point using the linear segments intersection
method,26 are shown in Fig 1S of ESI.†
1
preparation, once their structure was confirmed by H NMR
spectroscopy.
Aminonitrile, 11a. This was obtained as a yellow oil from
2.0 g (7.08 mmol) of imine 10a. dH (CDCl3) 2.02–2.10 (2 H, m),
2.59–2.93 (4 H, m), 4.59 (1 H, br s), 4.63 (1 H, br s), 6.72 (2 H,
dd, J1 = 8.1 Hz, J2 = 1.2 Hz), 6.82 (2 H, m), 7.08–7.21 (4 H, m).
Aminonitrile, 11b. This was obtained as a yellow oil from
2.49 g (8.40 mmol) of imine 10b. dH (CDCl3) 1.59–1.78 (4 H, m),
2.52–2.95 (4 H, m), 4.62 (1 H, br s), 4.95 (1H, br s), 6.71–6.88
(4H, m), 7.08–7.27 (4 H, m).
Aminonitrile, 11c. This was obtained as a yellow oil from
3.03 g (8.80 mmol) of imine 10c. dH (CDCl3) 3.74–3.96 (4 H, m),
4.58 (1 H, br s), 4.62 (1 H, br s), 6.73 (2 H, m), 6.85 (2 H, m),
7.09–7.23 (4 H, m), 7.24 (4 H, s).
Determination of stability constants by potentiometry
Potentiometric titrations were described in detail elsewhere.27
Due to the low solubility of ligands in acid medium, all data
were obtained by back-titration with aqueous 0.0500 M HCl
standardized titrant. Approximately 10–20 mg of chelating
agents were weighted to the nearest 0.01 mg and were dissolved
using four or six equivalents of NaOH (0.200 M). When appro-
priate, Ca(II) or Mg(II) solutions were added in ligand:metal
(1:1) and (1:10) ratio. The solutions were diluted to a final
volume of 50.0 cm3. A volume of 25 cm3 of the experimental
solution was back-titrated to pH 2.5 or until precipitation of
ligand occurred.
General procedure for the synthesis of amino acids 6–8
Concentrated aqueous HCl (12 M) was added over the freshly
prepared aminonitrile 11 in a 30:1 molar ratio. The mixture
was heated at 50–60 °C for 6 h and then water was added in a
volume equal to the acid. The resultant mixture was refluxed for
6 h. Amino acids 6–8 were obtained as hydrochlorides and as
a mixture of meso and racemic diastereomers. The free amino
acids could be obtained also as a diastereomeric mixture by
precipitation at pH 3.0 to 4.5 with 6 M NaOH. The solids were
filtered, washed successively with H2O, EtOH and acetone, and
finally dried in vacuo.
All formation constants, except for the protonation constants
corresponding to phenol dissociations, were calculated using the
FORTRAN program BEST.27,28
Propylenediamine-N,N-bis(2-hydroxyphenyl)acetic acid
(PDDHA) 6
Spectrophotometric equilibrium measurements
The hydrolysis of 2.93 g (8.0 mmol) of nitrile 11a yielded 3.1 g
(86% yield) of 11a as its hydrochloride. The free amino acid
(1.04, 11%) was isolated as a white solid by precipitation at
pH 4.3. mmax/cm−1 (KBr) 3402, 3066, 1632; dH (DMSO-d6–TFA)
2.12–2.21 (2 H, m), 2.85–3.00 (4 H, m), 5.15 (2 H, br s), 6.89 (2
H, m), 7.00 (2 H, m), 7.24–7.35 (4 H, m); dC (DMSO-d6–TFA)
21.7, 43.0, 58.0, 115.5, 117.2, 119.1, 130.0, 130.9, 155.5, 169.2.
Found: C, 60.71; H, 5.80; N, 7.31. Calc. for C19H22N2O6: C,
60.95; H, 5.92; N, 7.48%.
The first and second protonation constants were measured
spectrophotometrically,21 since the combination of protons with
the phenolic groups are accompanied by extensive changes in the
absorption spectra. For each ligand, ten-to-twelve 1 × 10−4
M
solutions were prepared and pH adjusted from 10.0 to 13.8 with
in 0.3–0.5 pH intervals. 250–400 nm spectra were obtained for
each free ligand in a Shimazdu UV-VIS spectrophotometer. The
wavelength on the maximum absorbances and molar absorptivi-
ties of L4− and LH22− species were initially estimated at pH 13.5
and 10, respectively, for each chelating agent (at these pHs the
other species are in low concentration) and used as imput for
the calculations. The spectroscopy equilibrium curves and wave-
length chosen for the determination of the first two phenolate
protonations are shown in Fig. 2S and Table 2S of ESI.†
Butylenediamine-N,N-bis(2-hydroxyphenyl)acetic acid
(BDDHA) 7
The hydrolysis of 3.17 g (9.0 mmol) of nitrile 11b yielded
3.1 g (71% yield) of 7 as its hydrochloride. The free amino acid
(1.89 g, 54%) was isolated as a white solid by precipitation at pH
4.4. mmax/cm−1 (KBr) 3404, 3045, 1626; dH (DMSO-d6–TFA) 1.69
(4 H, m), 2.91 (4 H, m), 4.95 (2 H, br s), 6.85–6.91 (4 H, m), 7.19–
7.27 (4 H, m); dC (DMSO-d6–TFA) 21.9, 45.0, 58.1, 115.5, 117.0,
119.2, 129.9, 130.9, 155.3, 169.1. Found: C, 61.54; H, 6.10; N,
7.13. Calc. for C20H24N2O6: C, 61.84; H, 6.23; N, 7.21%.
Stability constants (KFeL, KFeHL, KFe(OH)L, KCuL, KCuHL and
2
KCuH L) for the chelates were calculated from spectrophoto-
metric data obtained after base titration and using the
theoretical model presented by Yunta et al.6 The experimental
iron-chelate solution (1 × 10−4 M; 25 mL) was placed in a 50-cm3
thermostated jacketed reaction vessel. For the Fe(III) chelate,
the experimental solution was titrated with aqueous 0.200 M
NaOH titrant to pH 12. The absorbance of the solution was
measured at 480 nm at each 0.05–0.1 pH interval, depending on
the curve zone.
(p,p-Xylylene)diamine-bis(2-hydroxyphenyl)acetic acid
(XDDHA) 8
The hydrolysis of 6.22 g (15.6 mmol) of nitrile 11c yielded 7.7 g
(98% yield) of 8 as its hydrochloride. The free amino acid (4.18 g,
62%) was isolated by precipitation at pH 4.7. mmax/cm−1 (KBr)
3423, 3115, 1618; dH (DMSO-d6–TFA) 4.02 (4 H, br s), 4.87 (2
H, br s), 6.71–6.85 (4 H, m), 7.07–7.18 (4 H, m), 7.30 (4 H, s); dC
(DMSO-d6–TFA) 48.9, 58.6, 117.0, 117.4, 123.1, 155.0, 157.4,
158.2, 159.0, 159.7, 168.8. Found: C, 66.34; H, 5.41; N, 6.29.
Calc. for C24H24N2O6: C, 66.04; H, 5.54; N, 6.42%.
25 cm3 of Cu(II)/chelate 1 × 10−3 M experimental solution, in
the same conditions used for the iron complex, were titrated with
aqueous 0.200 M HCl titrant until the solution was colorless or
precipitation was observed. The absorbance of the solution was
measured at 650 nm at 0.05–0.1 pH intervals, depending on the
curve zone. The potentiometric curves with Fe(III) and Cu(II) are
shown in Figs. 3S and 4S of ESI.†
3 7 4 6
D a l t o n T r a n s . , 2 0 0 4 , 3 7 4 1 – 3 7 4 7