Inorganic Chemistry
Article
in distilled water, basified with 4 M NaOH until pH ∼12, and then
literature. Our results suggest that this is likely related to the
difference in the structure of the two Cu(I) complexes. Finally,
the results of our studies suggest that S-coordination of the
thiazolyl groups to either Cu(I) or Cu(II) does not occur. Our
ongoing work is dedicated to finding the adequate chelate
design to provide such behavior: two options consisting of
changing the size of the macrocyclic ring (using other
polyazamacrocycles) to modulate the position of the metal
center, or lengthening the arm (introducing ethylthiazolyl arms
rather than methylthiazolyl) to facilitate a coordination
inversion, may be envisaged. Additional efforts are also devoted
to introduce additional hydrophilic groups to increase the
solubility of such chelators in water when necessary. Anyway,
when compared to other ligands reported in the literature
including our own picolinate chelators, the thiazolyl ligands,
especially te2th, offer quite good properties, especially in the
kinetic and electrochemical inertness, while maintaining an
equivalent thermodynamic stability and a copper(II) selectivity
over zinc(II), suggesting promising results once the chelator
design is improved.
1
extracted with CHCl3 (3 × 30 mL). H NMR (CDCl3, 295 K, 300
MHz): δ(ppm) = 7.54 (d, J = 3.3 Hz, 1 H, th), 7.14 (d, J = 3.3 Hz, 1
H, th), 3.82 (s, 2 H, −CH2− th), 2.74−2.44 (m, 20 H), 1.85−1.66 (m,
2 H, β-CH2 cyclam), 1.58 (t, J = 5.4 and 5.4 Hz, 2 H, β-CH2 cyclam).
13C NMR (CDCl3, 295 K, 75.5 MHz): δ(ppm) = 169.40 (quaternary
C, th), 142.05, 119.35 (tertiary C, th), 77.59, 77.16, 76.73, 55.18,
54.40, 51.98, 50.70, 49.08, 48.60, 48.04, 47.66, 47.00, 43.51 (secondary
C), 28.52, 26.09 (secondary C, β-CH2 cyclam). HRMS: m/z 298.2060,
calcd C14H28N5S+ (MH+) 298.2060; m/z 149.6069 ([M + 2H]2+),
calcd C14H29N5S2+ 149.6066.
1,8-Bis(thiazol-2-ylmethyl)-1,4,8,11-tetraazatricyclo-
[9.3.1.14,8]hexadecane-1,8-diium bromide (5). Cyclam bisformyl
4 (0.241 g, 1.07 mmol) was added to a solution of 1 (0.459 g, 2.4
equiv, 2.58 mmol) in 15 mL of freshly distilled acetonitrile. The
mixture was heated to reflux during 4 days. The pale yellow precipitate
was isolated by filtration, washed with acetonitrile, and dried under
1
vacuum, to give 0.421 g of 5 (68%) as a white solid. H NMR (D2O,
295 K, 300 MHz): δ(ppm) = 7.88 (d, J = 3.4 Hz, 2H, th), 7.57 (d, J =
3.4 Hz, 2H, th), 4.16 (s, 4H, −CH2− th), 3.34−2.85 (m, 16 H), 2.06−
1.89 (m, 4H, β-CH2 cyclam). 13C NMR (D2O, 295 K, 75.5 MHz):
δ(ppm) = 144.67, 124.03 (tertiary C, th), 84.52 (secondary C, −CH2−
bisformyl), 57.93, 55.73, 50.72, 47.88 (secondary C); 25.60 (secondary
C, β-CH2 cyclam). HRMS (ESI+): m/z 395.2048 ([M − formyl
+
bridges + H])+ calcd C18H31N6S2 395.2046; m/z 198.1066 ([M −
EXPERIMENTAL SECTION
■
2+
formyl bridges + 2H]2+), calcd C18H32N6S2 198.1059.
General Methods. Reagents used for the synthesis were purchased
from Acros Organics and Sigma-Aldrich and used without further
purification. The reagent cyclam was purchased from CheMatech
(Dijon, France). Acetonitrile, toluene, and dichloromethane were
distilled before use. Aluminum oxide (Sigma-Aldrich, activated,
neutral, Brockmann I) was used for column chromatography.
Precursors 2-bromomethyl-thiazole (1),17 decahydro-3H-2a,5a,8,11a-
tetraaza-2a1-phosphacyclonona[cd]indene 2a1-oxide (2),18 and
1,4,8,11-tetraazatricyclo[9.3.1.14,8]hexadecane (4)19 were synthesized
according to the literature methods. The following instruments were
used for the characterization. For NMR, 1H, 31P, and 13C NMR spectra
1,8-Bis(thiazol-2-ylmethyl)-1,4,8,11-tetraazacyclotetrade-
cane (te2th). Compound 5 (0.305 g, 0.53 mmol) was dissolved in 4
M NaOH (30 mL) and stirred during 12 h. The mixture was extracted
with CHCl3 (3 × 50 mL), and the combined organic extracts were
dried on MgSO4. The solvent was evaporated to give a yellow
precipitate. The solid was dissolved in freshly distilled acetonitrile, and
the insoluble impurities were filtered off, to give 0.533 g of te2th
1
(84%) as a pale yellow solid. H NMR (CDCl3, 298 K, 300 MHz):
δ(ppm) = 7.51 (d, 2 H, th), 7.08 (d, 2 H, th), 3.82 (s, 4 H, −CH2−
th), 2.59−2.43 (m, 16 H, α-CH2 cyclam), 1.68−1.65 (m, 4 H, β-CH2
cyclam). 13C NMR (CDCl3, 298 K, 75.5 MHz): δ(ppm) = 168.28
(quaternary C, th), 142.23, 119.25 (tertiary C, th), 54.26, 54.09, 50.18,
48.25, 47.21 (secondary C), 25.84 (secondary C, β-CH2 cyclam).
1
were recorded with Bruker Avance 500 (500 MHz for H), Bruker
Avance III HD 500 (500 MHz for 1H), or Bruker DRX 300 (300 MHz
for 1H) spectrometers. For high-resolution mass spectrometry, a
HRMS Q-Tof MaXis instrument was used, with sources ESI, APCI,
APPI, nano-ESI (at the Institute of Organic and Analytic Chemistry,
ICOA).
+
HRMS (ESI+): m/z 395.2044 ([M + H]+), calcd C18H31N6S2
395.2046; m/z 198.1060 ([M + 2H]2+), calcd C18H32N6S22+ 198.1059.
CAUTION! Although no problem arose during our experiments,
perchlorate salts and their metal complexes are potentially explosive and
should be handled with great care and in small quantities.40
8-(Thiazol-2-ylmethyl)decahydro-3H-2a,5a,8,11a-tetraaza-
2a1-phosphacyclonona[cd]indene-2a1-oxide (3). Phosphoryl
cyclam 2 (0.749 g, 3.07 mmol) was dissolved in 15 mL of dry
CH3CN, and K2CO3 (1.413 g, 3.3 equiv, 10.22 mmol) was added. The
mixture was cooled to 0 °C, and a solution of compound 1 (0.606 g,
1.1 equiv, 3.40 mmol) was added dropwise. The reaction was stirred at
room temperature during 48 h. The suspension was filtered, and the
solution was evaporated to dryness. The crude product was purified by
column chromatography in aluminum oxide (using CHCl3 as eluent)
to yield the desired compound 3 as a pale yellow precipitate (0.886 g,
85%). 1H NMR (CDCl3, 298 K, 300 MHz): δ(ppm) = 7.54 (d, J = 3.2
Hz, 1 H, th), 7.13 (d, J = 3.1 Hz, 1 H, th), 3.88−3.55 (m, 4 H), 3.25−
3.07 (m, 3 H), 3.06−2.32 (m, 11 H), 1.83−1.56 (m, 2 H, β-CH2
cyclam), 1.54−1.29 (m, 2 H, β-CH2 cyclam). 13C NMR (CDCl3, 295
K, 75.5 MHz): δ(ppm) = 170.73 (quaternary C, th), 141.86, 119.57
(tertiary C, th), 54.75, 53.02, 51.35, 51.07, 45.17 (d, 2JC−P = 15.4 Hz),
[Cu(te1th)](ClO4)2. Cu(ClO4)2·6H2O (0.038 g, 0.9 equiv, 0.10
mmol) was added to a solution of te1th·5HCl (0.054 g, 0.11 mmol) in
2 mL of distilled water, and the mixture was stirred at room
temperature during 48 h. After that, a small amount of K2CO3 was
added to the mixture, which was stirred at room temperature during 3
days. The reaction mixture was concentrated to dryness. The
impurities were precipitated by the addition of EtOH (5 mL) and
filtered off. Concentration of the filtrate led to [Cu(te1th)](ClO4)2 as
a violet precipitate (0.056 g; 97%). HRMS (ESI+): m/z 395.0964 ([M
+ (Cl)]+) calcd C14H27ClCuN5S+ 395.0966; m/z 180.0639 ([M]2+),
calcd C14H27CuN5S2+ 180.0636.
[Zn(te1th)](ClO4)2. Zn(ClO4)2·6H2O (0.046 g, 1.0 equiv, 0.12
mmol) was added to a solution of te1th·5HCl (0.058 g, 0.12 mmol) in
5 mL of distilled H2O. The pH was adjusted to 6 with NaOH, and the
sample was then heated to reflux during 48 h. After that, the reaction
mixture was allowed to cool to room temperature and then
concentrated to dryness. The crude product was dissolved in 2 mL
of MeOH and precipitated with Et2O. The precipitate was isolated by
filtration and dried under vacuum, to give 0.058 g of [Zn(te1th)]-
2
2
44.31 (d, JC−P = 11.0 Hz), 42.00, 41.73, 40.32 (d, JC−P = 3.4 Hz)
(secondary C), 26.00 (secondary C, β-CH2 cyclam), 21.81 (d, 2JC−P
=
2.2 Hz) (secondary C, β-CH2 cyclam). 31P NMR (CDCl3, 295 K,
121.5 MHz): δ(ppm) = 25.12. HRMS: m/z found 342.1514, calcd
C14H25N5OPS+ (MH+) 342.1512.
1
(ClO4)2 (85%), as a white solid. H NMR (D2O, pD ∼6, 298 K, 500
2-((1,4,8,11-Tetraazacyclotetradecan-1-yl)methyl)thiazole
(te1th). A solution of compound 3 (0.052 g, 0.15 mmol) in 3 M HCl
(10 mL) was stirred at room temperature for 12 h. The solution was
concentrated, and the residue was purified on an ion-exchange resin
(Dowex 1X2, 100−200 mesh) activated with Cl−, to give 0.065 g of
the desired compound as a yellow pale solid (te1th·5HCl, 89%). In
order to get the neutral form of the ligand, te1th·5HCl was dissolved
MHz): δ(ppm) = 8.06 (d, 1 H, th), 7.95 (d, 1 H, th), 3.82 (s, 2 H,
−CH2− th), 2.68−2.45 (m, 16 H), 3.03−2.36 (m, 11 H), 1.77−1.69
(m, 2 H, β-CH2 cyclam), 1.62−1.55 (m, 2 H, β-CH2 cyclam). 13C
NMR (D2O, pD ∼6, 298 K, 125.8 MHz): δ(ppm) = 175.18
(quaternary C, th), 141.52, 126.14, 125.95 (tertiary C, th), 63.45,
62.09, 60.02, 58.39, 57.55, 55.88, 55.13, 54.46, 53.95, 53.01, 52.78,
J
Inorg. Chem. XXXX, XXX, XXX−XXX