Synthesis, solution and electrochemical behaviour of new aza-crown ethers derived from biphenyl

Article abstract of DOI:10.1039/a906342k

Macrocyclic ligands L¹-L⁴ containing biphenyl units have been synthesized. Potentiometric and voltametric studies in the presence and the absence of transition metal cations have been carried out. The relationship between the conform

Full text of DOI:10.1039/a906342k

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Synthesis, solution and electrochemical behaviour of new
aza-crown ethers derived from biphenyl
Ana M. Costero,*a Elena Monrabal,a Cecilia Andreu,a Ramón Martínez-Máñez,b Juan Soto,b
Miguel Padilla-Tosta,b Teresa Pardo,b Luis E. Ochandoc and José M. Amigóc
a Departamento de Química Orgánica, Facultad de Farmacia, Universitat de València,
Vicente Andrés Estellés s/n, 46100-Burjassot, Valencia, Spain
b Departamento de Química, Universidad Politécnica de Valencia, Camino de Vera s/n,
46071-Valencia, Spain
c Sección Departamental de Geología, Facultad de Química, 46100-Burjassot, Valencia, Spain
Received 4th August 1999, Accepted 13th December 1999
Macrocyclic ligands L1–L4 containing biphenyl units have been synthesized. Potentiometric and voltametric
studies in the presence and the absence of transition metal cations have been carried out. The relationship
between the conformation of the ligand and oxidation states has been also considered. The crystal structure
of [HgL2(CN)2]ؒ2Hg(CN)2 has been elucidated by X-ray diffraction techniques.
chromatography was carried out on SDS 60 A-CC silica gel
and on Scharlau activated neutral aluminium oxide (activity
degree 1).
Introduction
A combination of coronands and suitable redox-active groups
has proved to be a good method for the development of recep-
tors for the electrochemical sensing of substrates.1 The strategy
includes the selection of suitable binding sites, well known for
displaying large affinity for target guests, and their functionalis-
ation with redox-active groups.2 The most widely redox-active
group used for this purpose has probably been ferrocene.3
For instance, the functionalisation with ferrocenyl groups of
polyamines has proved to be a good approach for the
preparation of selective receptors for electrochemical detection
of transition metal ions and anions in aqueous environments.4,5
Recently, the functionalisation with ferrocenyl groups of
aza-oxa macrocycles led to molecules for the selective
electrochemical sensing of heavy metal ions of environmental
Melting points were measured on a Cambridge Instrument
and a Reichter Termovar. NMR spectra were recorded on
Bruker AC-250 and Varian Unity-300/400 spectrometers.
Chemical shifts are reported in ppm downfield from TMS.
Spectra taken in CDCl3 were referenced to either TMS or
residual CHCl3. When the spectra were recorded in (CD3)2CO,
the residual solvent was taken as reference. Mass spectra were
taken on a VG-AUTOSPEC mass spectrometer.
Electrochemical data were obtained with a programmable
function generator Tacussel IMT-1, connected to a Tacussel
PJT 120-1 potentiostat. The working electrode was platinum
with a saturated calomel reference electrode separated from
the studied solution by a salt bridge containing the solvent/
supporting electrolyte. The auxiliary electrode was a platinum
wire. Potentiometric titrations were carried out in dioxane–
water (70:30 v/v, 0.1 mol dmϪ3 KNO3) using a water-
thermostatted (25.0 0.1 ЊC) reaction vessel under nitro-
gen. The titrant was added using a Crison microburette
2031. The potentiometric measurements were conducted
using a Crison 2002 pH-meter and a combined glass electrode.
The titration system was automatically controlled by a PC
computer using a program that monitors the e.m.f. values
and the volume of titrant added. The electrode was calibrated
as a hydrogen concentration probe by titration of well
known amounts of HCl with CO2-free KOH solution and
determining the equivalent point by Gran’s method8 which
gives the standard potential EЈ0 and the ionic product of
water (KЈw = [Hϩ][OHϪ]). The concentration of the metal
ion solutions was determined using standard methods. The
computer program SUPERQUAD9 was used to calculate
the protonation and stability constants. The titration curves
for each system (ca. 250 experimental points corresponding to
at least three titration curves, pH = Ϫlog[H] range investigated
2–10, concentration of the ligand and metal ion was ca.
1.2 × 10Ϫ3 mol dmϪ3) were treated either as a single set or as
separated entities without significant variations in the values of
the stability constants. Finally, the set of data were merged
together and treated simultaneously to give the stability
constants.
importance such as Hg2ϩ 6
.
We have recently reported, for the first time, the use of 4,4Ј-
bis(dimethylamino)biphenyl as a redox-active group in redox-
responsive molecules.7 This group was covalently attached
to crown ethers for electrochemical sensing of alkali and
alkaline-earth cations. An interesting selective cathodic shift
was found for Mg2ϩ with some 4,4Ј-bis(dimethylamino)bi-
phenyl-containing receptors. The 4,4Ј-bis(dimethylamino)bi-
phenyl group shows two characteristics which are not usually
found in other redox-active groups such as ferrocene; (i) oxid-
ation can induce coplanarity in the aromatic rings and (ii)
the dimethylamino groups can also display co-ordination
towards substrates. We have now extended our previous work
on biphenyl derivatives and have synthesised new aza-oxa
macrocycles containing bis(dimethylamino)biphenyl groups
and have studied their solution and electrochemical behaviour
in the presence of Ni2ϩ, Cu2ϩ, Zn2ϩ, Cd2ϩ, Pb2ϩ and Hg2ϩ in
aqueous and non aqueous environments.
Experimental
General
All commercially available reagents were used without further
purification. Air- and/or water-sensitive reactions were per-
formed in flame-dried glassware under argon. Tetrahydrofuran
was distilled from Na–K amalgam prior to use. Column
J. Chem. Soc., Dalton Trans., 2000, 361–367
This journal is © The Royal Society of Chemistry 2000
361

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1
Synthesis of 2,2Ј-bis(chloromethyl)-4,4Ј-bis(dimethylamino)-
(0.346 g, 51%). H NMR (250 MHz, CDCl3) δ 6.95 (2H, d,
J = 8.4, Ar-H), 6.92 (2H, d, J = 2.8, Ar-H), 6.65 (2H, dd,
J1 = 8.4, J2 = 2.8, Ar-H), 4.35 (2H, AB, J = 11.9, Ar-CHA), 4.26
(2H, AB, J = 11.9, Ar-CHB), 3.64–3.40 (12H, m, CH2O), 2.98
(12H, s, Ar-NCH3), 2.79 (2H, ddd, J1 = 13.5, J2 = 6.4, J3 = 4.3,
CHAЈN), 2.64 (2H, ddd, J1 = 13.5, J2 = 6.4, J3 = 4.3, CHBЈN), 2.33
(3H, s, NCH3). 13C NMR (62.5 MHz, CDCl3) δ 149.7 (s), 137.6
(s), 130.7 (d), 128.0 (s), 112.0 (d), 111.1 (d), 71.4 (t), 70.2 (t),
69.8 (t), 68.4 (t), 56.1 (t), 43.3 (q), 40.6 (q). HRMS (EIϩ). Calc.
for C27H41N3O4: m/z 471.3097. Found: m/z 471.3093.
biphenyl 2
Thionyl chloride (25 ml) was placed in a flask containing 2,2Ј-
bis(hydroxymethyl)-4,4Ј-bis(dimethylamino)biphenyl 110 (2.0 g,
6.66 mmol) previously cooled in an ice-water bath. The solution
was stirred at room temperature overnight and then poured into
ice-water (100 ml). The mixture was made basic with sodium
carbonate and extracted with ethyl acetate (3 × 30 ml). The
organic phase was dried with sodium sulfate and the solvent
was evaporated. The crude product was purified by chromato-
graphy (neutral alumina, hexane–ethyl acetate 9:1) to give 2 as a
white solid (2.02 g, 90%). mp 120–122 ЊC. 1H NMR (250 MHz,
CDCl3) δ 7.10 (2H, d, J = 8.4, Ar-H), 6.86 (2H, d, J = 2.7,
Ar-H), 6.72 (2H, dd, J1 = 8.4, J2 = 2.7, Ar-H), 4.40 (2H, AB,
J = 11.0, Ar-CHA), 4.30 (2H, AB, J = 11.0 Hz, Ar-CHB), 2.98
(12H, s, NCH3). 13C NMR (62.5 MHz, CDCl3) δ 150.1 (s), 136.7
(s), 131.6 (d), 127.6 (s), 113.2 (d), 112.4 (d), 45.4 (t), 40.5
(q). HRMS (CIϩ): calc. for C18H22Cl2N2 m/z 336.1160; found
336.1154.
Synthesis of L3
This product was prepared following the general procedure
from 6-aza-3,9,12-trioxatetradecane-1,14-diol (0.218 g, 0.92
mmol) and 2,2-bis(chloromethyl)-4,4Ј-bis(dimethylamino)-
biphenyl (0.310 g, 0.92 mmol). The compound was isolated as a
brown oil after purification by chromatography (0.078 g, 17%).
1H NMR (250 MHz, CDCl3) δ 6.98–6.94 (2H, m, Ar-H), 6.87
(2H, d, J = 2.4 Hz, Ar-H), 6.69–6.65 (2H, m, Ar-H), 4.46–4.23
(4H, m, Ar-CH2), 3.88–3.38 (17H, CH2O, NH), 3.15–2.87 (4H,
m, CH2N), 2.99 (12H, s, NCH3). 13C NMR (62.5 MHz, CDCl3)
δ 149.7 (2 × s), 137.1 (s), 136.8 (s), 130.8 (2 × d), 128.2 (s), 128.1
(s), 112.2 (d), 112.0 (d), 111.4 (2 × d), 71.6 (t), 71.5 (t), 70.4 (t),
70.1 (t), 70.0 (t), 69.9 (t), 69.3 (t), 69.0 (t), 65.8 (t), 47.6 (2 × t),
40.7 (q). HRMS (EIϩ). Calc. for C28H43N3O5: m/z 501.3203.
Found: m/z 501.3192.
Synthesis of N-methyl-6-aza-3,9,12-trioxatetradecane-1,14-diol
6
Sodium triacetoxyborohydride (4.016 g, 18.95 mmol) was
added to a solution of 6-aza-3,9,12-trioxatetradecane-1,14-diol
(0.451 g, 1.90 mmol) and aqueous formaldehyde (30%, 0.17 ml,
1.90 mmol) in 1,2-dichloroethane (11 ml). The mixture was
stirred at room temperature for 3.5 h. Then, it was poured into
sodium hydroxide (20 ml, 10%) and evaporated until dryness.
The residue was washed with THF and the organic solution was
dried and then evaporated to give the product as a yellow oil
Synthesis of L4
This product was prepared following the general procedure
from 2,2Ј-bis(chloromethyl)-4,4Ј-bis(dimethylamino)biphenyl
(0.270 g, 0.80 mmol) and N-methyl-6-aza-3,9,12-trioxatetra-
decane-1,14-diol (0.210 g, 0.80 mmol). The compound was isol-
ated as a yellow oil after chromatographic purification (neutral
1
(0.396 g, 83%). H NMR (250 MHz, CDCl3) δ 4.07 (2H, br s,
OH), 3.69–3.50 (16H, m, CH2O), 2.60 (2H, t, J = 5.1, CH2N),
2.58 (2H, t, J = 4.9 Hz, CH2N), 2.26 (3H, s, NCH3). 13C NMR
(62.5 MHz, CDCl3) δ 71.9 (t), 71.6 (t), 69.5 (2 × t), 68.0 (t), 67.5
(t), 60.5 (t), 60.4 (t), 56.5 (t), 56.1 (t), 42.1 (q). HRMS (CIϩ):
calc. for C11H26NO5 m/z 252.1811; found 252.1812.
1
alumina) (0.153 g, 37%). H NMR (250 MHz, CDCl3) δ 6.97
(2H, d, J = 8.4, Ar-H), 6.95 (2H, d, J = 2.7, Ar-H), 6.07 (2H, dd,
J1 = 8.4, J2 = 2.7 Hz, Ar-H), 4.34 (2H, s, Ar-CH2), 4.33 (2H, s,
Ar-CH2), 3.64–3.47 (16H, m, CH2O), 3.00 (12H, s, Ar-NCH3),
2.35 (3H, s, NCH3). 13C NMR (62.5 MHz, CDCl3) δ 149.6
(2 × s), 137.5 (s), 137.1 (s), 130.7 (2 × t), 128.0 (s), 127.8 (s),
112.2 (d), 111.4 (d), 111.3 (d), 110.9 (d), 71.4 (t), 71.1 (t), 70.4
(t), 70.3 (2 × t), 70.1 (t), 69.4 (2 × t), 67.4 (t), 56.1 (t), 55.8 (t),
42.2 (q), 40.5 (q). HRMS (CIϩ). Calc. for C29H45N3O5: m/z
515.3359. Found: m/z 515.3378.
Synthesis of L1
General procedure. Dry sodium hydride (0.214 g, 8.90 mmol)
was added under inert atmosphere to a solution of 6-aza-3,9-
dioxaundecane-1,11-diol (0.172 g, 0.89 mmol) in dry THF (40
ml). The mixture was heated under reflux for 2 h and then,
sodium iodide (0.013 g, 0.09 mmol) was added. Subsequently,
a solution of 2,2-bis(chloromethyl)-4,4Ј-bis(dimethylamino)-
biphenyl (0.30 g, 0.89 mmol) in dry THF (50 ml) was added
dropwise for 3 h. The reaction was additionally heated for 17 h.
The reaction was quenched with water and then the solvent was
evaporated under vacuum. The residue was dissolved in ethyl
acetate (75 ml) and the organic phase was washed with water
(3 × 25 ml) and dried with sodium sulfate. The solvent was elim-
inated under vacuum and the crude product was purified by
column chromatography (neutral alumina) to give L1 as a dark
Synthesis of the complexes
General procedure. One equivalent of the salt in acetone was
added to one equivalent of the ligand in acetone. In each case
the minimum amount of acetone to dissolve the ligand and the
salt were employed. The mixture was stirred in a stoppered tube
for 4 h and then the solvent was slowly evaporated to give the
corresponding complex.
1
yellow oil (0.110 g, 27%). H NMR (250 MHz, CDCl3) δ 6.95
1
L2ؒHg(CN)2. Yellow solid. mp 214–215 ЊC. H NMR (250
(2H, d, J = 8.4, Ar-H), 6.84 (2H, d, J = 2.6, Ar-H), 6.65 (2H, dd,
J1 = 8.4, J2 = 2.6, Ar-H), 4.48 (2H, AB, J = 11.7, Ar-CHA), 4.20
(2H, AB, J = 11.7 Hz, Ar-CHB), 3.78–3.30 (13H, m, CH2O,
NH), 3.11–3.06 (4H, m, CH2N), 2.98 (12H, s, NCH3). 13C
NMR (62.5 MHz, CDCl3) δ 149.6 (s), 136.7 (s), 130.9 (d), 128.0
(s), 112.2 (d), 111.3 (d), 71.7 (t), 70.2 (t), 69.4 (t), 66.0 (t), 47.7
(t), 40.5 (q). HRMS (EIϩ). Calc. for C26H39N3O4: m/z 457.2941.
Found: m/z 457.2944.
MHz, CD3OD) δ 6.91–6.68 (4H, m, Ar-H), 6.61 (2H, dd,
J1 = 8.4, J2 = 2.6 HZ, Ar-H), 4.50–4.10 (4H, m, Ar-CH2), 3.80–
3.08 (12H, m, CH2O), 2.89 (12H, s, Ar-NCH3), 3.00–2.67 (4H,
m, CH2N), 2.08 (3H, s, NCH3). 13C NMR (62.5 MHz, CD3OD)
δ 152.8 (s), 144.9 (s, CN), 136.8 (s), 133.8 (d), 130.6 (s), 117.7
(d), 114.8 (d), 72.7 (2 × t), 72.0 (t), 68.2 (t), 60.9 (t), 42.7 (q),
39.2 (q). Anal. Calc. for C29H41HgN5O4: C, 47.98; H, 5.70; N,
9.65. Found: C, 47.93; H, 5.68; N, 9.69%.
Synthesis of L2
L2ؒCd(NO3)2. Yellow wax. 1H NMR (250 MHz, CD3OD)
δ 6.84 (2H, d, J = 8.6, Ar-H), 6.83 (2H, d, J = 2.5, Ar-H),
6.65 (2H, dd, J1 = 8.6, J2 = 2.5, Ar-H), 4.33 (2H, AB, J = 12.0,
Ar-CHA), 4.19 (2H, AB, J = 12.0 Hz, Ar-CHB), 3.60–2.70 (16H,
m, CH2O, CH2N), 2.88 (12H, s, Ar-NCH3), 2.59 (3H, s, NCH3).
13C NMR (62.5 MHz, CD3OD) δ 151.5 (s), 138.1 (s), 132.1 (d),
This product was prepared following the general procedure
from N-methyl-6-aza-3,9-dioxaundecane-1,11-diol (0.296 g,
1.43 mmol) and 2,2-bis(chloromethyl)-4,4Ј-bis(dimethylamino)-
biphenyl (0.482 g, 1.43 mmol). L2 was purified by column
chromatography (neutral alumina) and isolated as a yellow oil
362
J. Chem. Soc., Dalton Trans., 2000, 361–367

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130.1 (s), 114.1 (d),113.1 (d), 73.0 (2 × t), 71.5 (t), 70.9 (t), 65.5
(t), 56.7 (t), 42.5 (q), 41.1 (q). Anal. Calc. for C27H41CdN5O10:
C, 45.69; H, 5.83; N, 9.87. Found: C, 45.50; H, 5.73; N, 9.91%.
See http://www.rsc.org/suppdata/dt/a9/a906342k/ for crystal-
lographic files in .cif format.
Results and discussion
Synthesis
The preparation of aza-crown ethers L1–4 was accomplished by
the method outlined in Scheme 1. Treatment of 2,2Ј-bis(hydroxy-
L2ؒPb(NO3)2. Yellow wax. 1H NMR (250 MHz, CD3OD)
δ 6.86 (2H, d, J = 8.6, Ar-H), 6.83 (2H, d, J = 2.7, Ar-H), 6.68
(2H, dd, J1 = 8.6, J2 = 2.7, Ar-H), 4.50 (2H, AB, J = 10.6,
Ar-CHA), 4.29 (2H, AB, J = 10.6 Hz, Ar-CHB), 3.90–2.73 (16H,
m, CH2O, CH2N), 2.88 (12H, s, Ar-NCH3), 2.56 (3H, s, NCH3).
13C NMR (62.5 MHz, CD3OD) δ 151.6 (s), 137.1 (s), 132.5 (d),
129.6 (s), 114.9 (d),113.6 (d), 72.8 (2 × t), 71.9 (t), 70.4 (t), 57.9
(t), 42.0 (q), 41.0 (q). Anal. Calc. for C27H41PbN5O10: C, 40.34;
H, 5.14; N, 8.72. Found: C, 40.30; H, 5.13; N, 8.75%.
L4ؒHg(CN)2. Yellow wax. 1H NMR (250 MHz, CD3OD)
δ 6.88–6.87 (4H, m, Ar-H), 6.60 (2H, dd, J1 = 8.0, J2 = 2.6 Hz,
Ar-H), 4.20 (4H, s, Ar-CH2), 3.60–3.22 (16H, m, CH2O), 2.85–
2.65 (4H, m, CH2N), 2.84 (12H, s, Ar-NCH3), 2.33 (3H, s,
NCH3). 13C NMR (62.5 MHz, CD3OD) δ 151.6 (2 × s), 144.2 (s,
CN), 138.3 (s), 137.9 (s), 132.1 (2 × d), 130.0 (s), 129.5 (s), 113.9
(2 × d), 113.1 (2 × d), 73.5 (t), 73.0 (t), 73.0 (t), 72.1 (t), 71.8 (t),
71.2 (3 × t ), 71.0 (t), 66.9 (2 × t), 58.9 (2 × t), 41.2 (q), 39.6 (q).
Anal. Calc. for C31H45HgN5O5: C, 48.46; H, 5.90; N, 9.12.
Found: C, 48.40; H, 5.86; N, 9.18%.
L4ؒCd(NO3)2. Yellow wax. 1H NMR (250 MHz, CD3OD)
δ 6.83–6.77 (4H, m, Ar-H), 6.62 (2H, dd, J1 = 8.4, J2 = 2.7 Hz,
Ar-H), 4.35–4.15 (4H, m, Ar-CH2), 3.75–3.20 (16H, m, CH2O),
3.10–2.80 (4H, m, CH2N), 2.84 (12H, s, Ar-NCH3), 2.50 (3H, s,
NCH3). 13C NMR (62.5 MHz, CD3OD) δ 151.5 (2 × s), 138.4
(s), 138.0 (s), 132.1 (d), 132.2 (d), 130.2 (s), 130.0 (s), 113.2
(2 × d),112.9 (2 × d), 73.4 (t), 72.9 (t), 71.4 (3 × t), 71.0 (t), 70.7
(t), 70.0 (t), 65.6 (2 × t), 57.5 (2 × t), 41.5 (q), 41.1 (q). Anal.
Calc. for C29H45CdN5O11: C, 46.31; H, 6.03; N, 9.31. Found: C,
45.27; H, 5.98; N, 9.36%.
L4ؒPb(NO3)2. Yellow wax. 1H NMR (250 MHz, CD3OD)
δ 6.84–6.76 (4H, m, Ar-H), 6.66–6.61 (2H, m, Ar-H), 4.40–4.00
(4H, m, Ar-CH2), 3.70–3.22 (16H, m, CH2O), 3.10–2.70 (4H,
m, CH2N), 2.85 (12H, s, Ar-NCH3), 2.60 (3H, s, NCH3). 13C
NMR (62.5 MHz, CD3OD) δ 151.5 (2 × s), 138.1 (s), 137.6 (s),
132.4 (2 × d), 130.8 (2 × s), 114.8 (d), 114.3(d), 113.8 (2 × d),
73.5 (t), 73.0 (t), 71.7 (4 × t), 70.8 (t), 70.5 (t), 65.6 (2 × t), 57.2
(2 × t), 41.6 (q), 41.5 (q). Anal. Calc. for C29H45PbN5O11: C,
41.13; H, 5.36; N, 8.27. Found: C, 41.05; H, 5.35; N, 8.30%.
Scheme 1
methyl)-4,4Ј-dimethylaminobiphenyl10 1 with thionyl chloride
produced a 90% yield of dichloride 2. Cyclisation of 2 with the
appropriate chains under high dilution conditions provided the
cyclic ligands L1–4. Compounds 3,13 414 and 515 were prepared
as described in the literature. On the other hand, compound
6 was obtained by treating 5 first with aqueous formaldehyde
and then with sodium triacetoxyhydroborate16 (Scheme 2).
Crystallographic data collection and structure determination
C29H41HgN5O4 ϩ 2C2HgN2 M = 976.89, triclinic, space group
¯
P1 (no. 2), a = 10.941(3), b = 11.270(3), c = 16.785(3) Å, α =
71.86(2), β = 72.74(2), γ = 68.98(2)Њ, Z = 2, V = 1795.7(8)
Å3, λ(Mo-Kα) = 0.71069 Å, T = 293(2) K, µ(Mo-Kα) = 8.582
mmϪ1. Data collection gave 6289 unique reflections of which
5191 with I > 2σ(I) were used in all calculations (R(int) =
0.0198). Lorentz-polarization and empirical absorption (Ψ
scans) corrections were made. The crystal structure was solved
by Patterson methods11 and refined by full-matrix least-square
techniques12 on F2. The non-hydrogen atoms were anisotropic-
ally refined. 60% of the hydrogen atoms were geometrically
constructed using the SHELXL-97 program with fixed iso-
tropic displacement parameters. The final wR(F2) was 0.1343,
R1 = 0.0463.
There are 464 refined parameters derived from the 5191 data,
a very high degree of over-determination so the precision of the
structure is high (e.s.d. values of the parameters are small). In a
final difference electron density map there are a few peaks of
size 4.920 e ÅϪ3 very close to the mercury atom (a commonly
observed feature for heavy atom structures, due largely to an
imperfect correction for strong absorption effects in the data).
CCDC reference number 186/1772.
Scheme 2
Mercury, cadmiun and lead complexes were prepared from
these compounds and their structural properties studied by
spectroscopic techniques and by X-ray diffraction.
J. Chem. Soc., Dalton Trans., 2000, 361–367
363

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Table 1 Selected bond lengths (Å) and angles (Њ) for [HgL2(CN)2]ؒ
2Hg(CN)2 with e.s.d.s in parentheses
Table 2 Stepwise protonation constants (log K) of L2 and L4 deter-
mined in dioxane–water (70:30 v/v) at 298.1 K in 0.1 mol dmϪ3 KNO3
a
Hg(1)–O(3)
Hg(1)–O(6)
Hg(1)–N(9)
3.217(8)
2.759(7)
2.637(9)
Hg(1)–O(3)
Hg(1)–O(13)
2.703(7)
3.032(7)
Reaction
L2
L4
L ϩ Hϩ = HLϩ
8.46(1)
8.25(2)
11.79(2)
—
L ϩ 2Hϩ = H2L2ϩ
L ϩ 3Hϩ = H3L3ϩ
HLϩ ϩ Hϩ = H2L2ϩ
H2L2ϩ ϩ Hϩ = H3L3ϩ
12.09(1)
14.48(3)
3.63
O(3)–C(4)–C(5)
C(4)–C(5)–O(6)
C(5)–O(6)–C(7)
O(6)–C(7)–C(8)
C(7)–C(8)–N(9)
C(8)–N(9)–C(11)
N(9)–C(11)–C(12) 112.2(11) C(8)–N(9)–C(11)–C(12)
C(11)–C(12)–O(13) 106.5(11) C(7)–C(8)–N(9)–C(11)
C(12)–O(13)–C(14) 115.7(9)
106.5(9)
107.2(8)
113.3(9)
O(13)–C(14)–C(15)
C(14)–C(15)–O(16)
O(3)–C(4)–C(5)–O(6)
109.1(10)
109.2(10)
63.4(12)
3.54
2.39
108.2(10) C(4)–C(5)–O(6)–C(7)
112.2(11) O(13)–C(14)–C(15)–O(16) 69.5(4)
106.6(10) C(12)–O(13)–C(14)–C(15) 175.0(11)
176.9(10)
a Units of
K
for process L ϩ nHϩ = HnLnϩ or HmL ϩ nHϩ
=
Hm ϩ nL(m ϩ n)ϩ are dm3n molϪn. Estimated experimental uncertainties of
log K values in parentheses.
164.4(12)
177.1(11)
Fig. 2 View of molecular structure for [HgL2(CN)2]ؒ2Hg(CN)2.
lists the stepwise protonation constants. Receptors L2 and L4
contain three nitrogen atoms; one in the macrocycle and two
associated with the biphenyl group. Three and two protonation
processes were found for receptors L2 and L4, respectively. The
first protonation constant can be attributed to the protonation
of the amino group in the aza-oxa crown cavity, whereas the
remaining protonation processes would occur at the amino
moieties attached to the bis(dimethylamino)biphenyl fragment.
This assignment is supported by some recent observations.7 We
have recently determined the protonation constants of a crown
ether derivative also containing a bis(dimethylamino)biphenyl
group, and two protonation constants were found (L ϩ Hϩ =
HLϩ, log K1 = 3.56(3) and HLϩ ϩ Hϩ = H2L2ϩ, log K2 = 2.0(1))
attributed to the protonation of the bisdimethylamino frag-
ments. These values are close to the logarithms of the second
and third basicity constants of L2 (3.63 and 2.69 respectively),
and reinforce the suggestion that the less basic processes are
related to the protonation of the dimethylamino groups.
Fig. 1 Molecular structure with crystallographic numbering scheme
for [HgL2(CN)2]ؒ2Hg(CN)2. Hydrogen atoms have been omitted for
clarity.
Crystallographic studies
X-Ray single-crystal studies were performed on the complex
L2ؒHg(CN)2 with selected bond lengths and angles given in
Table 1. A suitable crystal was obtained through slow diffusion
of hexane into a dichloromethane solution of the compound.
The structure shows that all the heteroatoms in the crown
moiety participate in coordination towards mercury (Fig. 1). In
addition the donor atoms in the ring are, on average, 0.1713 Å
from the heteroatom mean plane and do not alternate above
and below this main plane. In the complex the mercury atom
lies approximately in the heteroatom mean plane and it is not in
a central position within the cavity. The mercury atom is clearly
closer to N(9) (2.637 Å), O(6) and O(13) (2.759 and 2.703 Å,
respectively) than to O(3) and O(16) (3.217 and 3.032 Å,
respectively). In addition, the complex shows a very regular ring
conformation with almost all C–O bonds antiperiplanar. The
C–C–O angles are close to tetrahedral and the C–O–C angles
are somewhat larger, by contrast, the opposite situation is
observed for the C–C–N and C–N–C angles. The dihedral angle
formed by both aromatic rings is around 100Њ.
Solution studies directed to the determination of the stability
constants for the formation of complexes of L2 and L4 with
Ni2ϩ, Cu2ϩ, Zn2ϩ, Cd2ϩ, Pb2ϩ and Hg2ϩ were also carried out
in dioxane–water (70:30 v/v, 0.1 mol dmϪ3 potassium nitrate,
25 ЊC) (Table 3 for L2 and Table 4 for L4). Stability constants of
L4 with Cu2ϩ were not determined owing to the insolubility of
the Cu2ϩ–L4 system over a wide pH range. Both receptors form
stable complexes with all the metal ions studied. Fig. 3 shows
the distribution diagrams of the L4–Cd2ϩ and L4–Hg2ϩ systems.
Although the species [M(HL)]3ϩ, [M(L)(OH)]ϩ and [M(L)-
(OH)2] have been found to exist for all metal ions studied
(except for Hg2ϩ and L4), the species [M(L)]2ϩ were found to
exist only for some of the metal ions. The logarithm of the
stability constants found for the formation of the M(L4)2ϩ
The single crystal was obtained from a complex synthesised
in the presence of an excess of Hg(CN)2 and as a consequence
two additional molecules of Hg(CN)2 were present in the cell.
These molecules were located in special positions in the unit cell
of the crystal (Fig. 2).
complexes (M2ϩ ϩ L4 = M(L4)2ϩ) increases in the order Cd2ϩ
<
Pb2ϩ < Hg2ϩ with the latter appearing to form the most stable
complexes. The largest stability constant for the equilibrium
L ϩ M2ϩ = [M(L)]2ϩ is that for Hg2ϩ (log K = 8.15 when the
receptor is L4), whereas the logarithms of the stability constants
of the equilibrium L ϩ M2ϩ = [M(L)]2ϩ for Pb2ϩ and Cd2ϩ with
Cation binding studies
The protonation behaviour of receptors L2 and L4 was studied
in dioxane–water (70:30 v/v) (0.1 mol dmϪ3 potassium nitrate,
25 ЊC) owing to their insolubility in pure water and Table 2
364
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Table 3 Stability constants (log K) for the formation of Ni2ϩ, Cu2ϩ, Zn2ϩ, Cd2ϩ, Pb2ϩ and Hg2ϩ complexes of L2 in dioxane–water (70:30 v/v) at
25 ЊC in 0.1 mol dmϪ3 KNO3
a
Reaction
Ni2ϩ
Cu2ϩ
Zn2ϩ
Cd2ϩ
Pb2ϩ
Hg2ϩ
M2ϩ ϩ Hϩ ϩ L2 = M(HL2)3ϩ b
12.17(4)
—
Ϫ4.02(4)
Ϫ12.46(3)
12.63(4)
—
0.54(3)
Ϫ8.24(4)
12.62(4)
—
Ϫ1.86(3)
Ϫ8.24(4)
11.35(4)
—
Ϫ4.60(2)
Ϫ13.7(1)
12.02(5)
5.07(7)
Ϫ1.98(4)
Ϫ10.53(6)
12.90(2)
—
5.55(2)
Ϫ3.50(3)
M2ϩ ϩ L2 = M(L2)2ϩ c
M2ϩ ϩ L2 ϩ H2O = M(L2)(OH)ϩ ϩ Hϩ d
M2ϩ ϩ L2 ϩ 2H2O = M(L2)(OH)2 ϩ 2Hϩ e
a Experimental uncertainties of log K values in parentheses. b Units of K: dm6 molϪ2
.
c Units of K: dm3 molϪ1 d K dimensionless. e Units of K:
.
mol dmϪ3
.
Table 4 Stability constants (log K) for the formation of Ni2ϩ, Zn2ϩ, Cd2ϩ, Pb2ϩ and Hg2ϩ complexes of L4 in dioxane–water (70:30 v/v) at 25 ЊC in
a
0.1 mol dmϪ3 KNO3
Reaction
Ni2ϩ
Zn2ϩ
Cd2ϩ
Pb2ϩ
Hg2ϩ
M2ϩ ϩ Hϩ ϩ L4 = M(HL4)3ϩ b
11.39(7)
—
Ϫ4.82(11)
Ϫ12.73(3)
11.14(10)
—
Ϫ2.71(4)
Ϫ10.95(6)
11.18(2)
3.44(4)
Ϫ4.57(1)
Ϫ17.82(2)
11.14(9)
4.98(6)
Ϫ2.30(6)
Ϫ11.48(12)
—
M2ϩ ϩ L4 = M(L4)2ϩ c
8.15(3)
4.17(2)
Ϫ4.59(4)
M2ϩ ϩ L4 ϩ H2O = M(L4)(OH)ϩ ϩ Hϩ d
M2ϩ ϩ L4 ϩ 2H2O = M(L4)(OH)2 ϩ 2Hϩ e
Footnotes a–e as in Table 3.
Table 5 Stability constants (log (K/dm3 molϪ1) for the formation of
Zn2ϩ, Cd2ϩ and Pb2ϩ complexes of L5 and L6 in CH3OH–H2O (95:5 v/v,
0.1 M NEt4ClO4)
Reaction
Zn2ϩ
Cd2ϩ
Hg2ϩ
M2ϩ ϩ L5 = M(L5)2ϩ
M2ϩ ϩ L6 = M(L6)2ϩ
4.1
<4.0
<3.7
3.7
10.3
>12
order Cd2ϩ < Zn2ϩ < Hg2ϩ. Receptors L5 and L6 show larger
stability constants for Hg2ϩ for the formation of [M(L)]2ϩ
complexes (log K = 10.3 and >12) than for receptor L4 (log
K = 8.15). This can be attributed to the presence of geometrical
constraints in L4 owing to the presence of the electro-active
group. However, a larger cavity in L2 and L4 relative to L5 and
L6, and the use of different solvents (water for studies on L5 and
L6 and dioxane–water for L4), are among other factors which
may account for the different co-ordination behaviour found
for L2, L4 and L5, L6.
Both receptors L2 and L4, show similar stability constant
values with metal ions indicating that their coordination mode
is quite similar, despite the larger ring size of L4 relative to L2.
For instance, the logarithms of the stability constants for the
equilibrium L ϩ Pb2ϩ = [Pb(L)]2ϩ are 5.07 and 4.98, respect-
ively for receptors L2 and L4 (see Tables 3 and 4).
Fig. 3 Distribution diagrams for the L4–Cd2ϩ and L4–Hg2ϩ systems.
As it has been stated above, receptors L2 or L4 could co-ordin-
ate metal ions through the aza-oxa crown cavity or through the
dimethylamino groups. In order to elucidate the co-ordination
mode of these receptors, we have synthesised and isolated the
mercury, lead and cadmium complexes of L2 and L4, as well as
augmenting the co-ordination study by NMR analysis. Quali-
tative complexation experiments of Hg(CN)2 with ligands L2
and L4 were carried out in (CD3)2CO using NMR techniques.
The first observation was that the presence of a nitrogen atom
in the macrocycle gave rise to higher binding constants for the
ligands than for macrocycles containing only oxygen atoms.7,10
the receptor L4 are 4.98 and 3.44, respectively. This corresponds
to an expected solution behaviour and can be attributed to the
presence of N- and O-donor atoms in the macrocyclic cavity. It
has been reported that aza-oxa macrocycles generally display
larger stability constants with Hg2ϩ than with other common
metal ions. Table 5 lists the stability constants (log K) for the
formation of Zn2ϩ, Cd2ϩ and Hg2ϩ complexes with receptors L5
and L6 in CH3OH–H2O (95:5 v/v, 0.1 M NEt4ClO4).17 The
logarithm of the stability constant found for the formation of
the M(L5)2ϩ complexes (M2ϩ ϩ L5 = M(L5)2ϩ) increases in the
J. Chem. Soc., Dalton Trans., 2000, 361–367
365

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Thus, in ligands containing only oxygen atoms, the experiments
carried out by Rebek et al.18 and our own experiments demon-
strated that both the complex and the free ligand species were
observed in the 1H NMR spectra when a 1:1 stoichiometry was
used. By contrast, for ligands L2 and L4 only one species, the
1:1 complex, was present when a 1:1 stoichiometry was used
with ligand exchange being slow. Thus, signals corresponding
to both the free ligand and to the complex were observed when
the mercury:ligand stoichiometry was <1:1 in solution. Differ-
ent ratios of free ligand to complex were observed for each
studied stoichiometry. The NMR spectra showed that the metal
ions were complexed by the aza-oxa crown moiety but not by
the aromatic amines. Thus, signals corresponding to the
diastereotopic benzylic hydrogens that appeared as two separ-
ate doublets in the free ligand (L2) (δ 4.35, 4.26) become a
multiplet in the complex (L2ؒHg(CN)2) (δ 4.50–4.10). In addi-
tion, a downfield shift was observed not only for the methylene
groups of the coronand but also for the methyl group attached
to the N-donor atom in the macrocycle.
Complexation studies were also carried out using Cd(NO3)2
and Pb(NO3)2. The ionic character of these salts compared with
the covalent character of Hg(CN)2 appears not to influence the
complexation mode given that similar results were observed as
for Hg(CN)2, with the formation of strong complexes within
the aza-oxa crown cavity.
Electrochemical cation sensing studies
Fig. 4 Oxidation potential shift of the bis(dimethylamino)biphenyl
fragment of L2 as a function of the pH in the presence and absence of
of Cu2ϩ, Zn2ϩ, Cd2ϩ, Pb2ϩ, Ni2ϩ and Hg2ϩ
One of the most interesting features in receptors L2 and L4 is
the presence of redox-active groups near co-ordination sites.
These groups can be affected by the presence of closely bound
cationic guest species and transform receptor-substrate inform-
ation at the microscopic level into a macroscopic electro-
chemical response. Electrochemical experiments were per-
formed under the same experimental conditions as used for the
potentiometry. Over the pH range studied, receptors L2 and L4
show one redox process. The difference between anodic and
cathodic peak potentials and the ratio between the cathodic and
anodic intensities suggested that these redox processes are
reversible. Fig. 4 plots the oxidation potential shift (E1/2 meas-
ured from rotating disk techniques) of the bis(dimethylamino)-
biphenyl fragment of receptor L2 as a function of the pH in
the presence and absence of Cu2ϩ, Zn2ϩ, Cd2ϩ, Pb2ϩ, Ni2ϩ
and Hg2ϩ. The half-wave potential of the electro-active
groups is pH-dependent. The oxidation potential of L2 and L4
is anodically shifted when the pH is reduced. Such behaviour
has already been observed in related systems and can be attrib-
uted to the steady protonation of the three amino groups to
give charged ammonium fragments, which makes oxidation
more difficult.
.
the redox-active group and the metal ions in solution. The size
of the aza-oxa macrocyclic cavity, the number and topology of
the N- and O-donor atoms and the degree of protonation
would determine the strength of the complex. Upon oxidation
of the redox-active group a radical cation is formed which leads
to (i) an electrostatic repulsion between the radical cation and
the metal ion co-ordinated to the aza crown ether and (ii) a
conformational change of the ligand enabling both aromatic
rings to be in the same plane in order to allow for delocalisation
of the unpaired electron. These two effects will lead to an
oxidation potential shift for the bis(dimethylamino)biphenyl
fragment in the presence of metal ions. However, whereas
evaluation of the first effect is straightforward (the same effect
is also present in ferrocene-functionalised molecules) the
second factor is difficult to evaluate. The equation ∆E = (RT/
nF)ln(K/Kox) shows the relation between the binding constants
of the oxidised (Kox) and ‘reduced’ (K) forms and the electro-
chemical shift (∆E) and the relative value of K and Kox will
determine the sign of ∆E. Fig. 4 indicates a small cathodic
shift for the oxidation potential of the electro-active group in
the presence of some metal ions with respect to that of the
free receptor suggesting that Kox > K. This indicates that the
electrochemical response of receptors L2 and L4 is not only
influenced by electrostatic factors but also by conformational
changes which suggest that L2 and L4 are better receptors upon
oxidation.7
Electrochemical experiments performed in the presence of
metal ions does not substantially perturb the E1/2 vs. pH curve
of the free receptors (maximum shift in the pH range 4–6 but
with ∆E1/2 always <20 mV). This disappointing behaviour
contrasts with some recent results for aza-oxa macrocycles
functionalised with redox-active groups (ferrocene) which
display selective electrochemical sensing of Hg2ϩ over other
common water present transition metal ions.
We have recently reported that selective electrochemical
responses towards target metal ions can be related to (i) the
existence of pH ranges of selective complexation or (ii) the
presence of predominant receptor–metal complexes over a wide
pH range. Additionally, it would be expected that metal ions
that show different distribution diagrams would display differ-
ent electrochemical behaviour. Fig. 3 shows that the distribu-
tion diagrams of the L4–Hϩ–Cd2ϩ and L4–Hϩ–Hg2ϩ systems are
quite different, however, their electrochemical behaviour are
very similar and also closely resemble that shown by the free
receptor. In attempting to explain this low selectivity one
should consider the nature of the interaction process between
Conclusions
Receptors L1–4 containing an aza-oxa coronand and an electro-
active group derived from biphenyl have been synthesised and
characterised. L1–4 are able to complex transition metal cations
and stability constants have been determined in dioxane–water
(70:30 v/v, 0.1 mol dmϪ3 potassium nitrate, 25 ЊC). The electro-
chemical behaviour of receptors L1–4 has been discussed in
terms of electrostatic repulsion and conformational changes on
the ligand upon oxidation owing to the formation of a radical
cation. To the best of our knowledge, this is the first time that
studies relating to the use of 4,4Ј-bis(dimethylamino)biphenyl
366
J. Chem. Soc., Dalton Trans., 2000, 361–367

View Article Online
6 J. M. Lloris, R. Martínez-Máñez, T. Pardo, J. Soto and M. E.
as an electroactive group for the sensing of transition metal ions
has been carried out. New ligands containing more rigid chains
are being prepared in order to obtain more information relating
to the influence of oxidation on the ligand conformation.
Padilla-Tosta, Chem. Commun., 1998, 837; J. M. Lloris, A. Benito,
R. Martínez-Máñez, M. E. Padilla-Tosta, T. Pardo, J. Soto and
M. J. L. Tendero, Helv. Chim. Acta, 1998, 81, 2024.
7 A. M. Costero, C. Andreu, R. Martínez-Máñez, J. Soto, L. E.
Ochando and J. M. Amigó, Tetrahedron, 1998, 54, 8159.
8 P. Gans, A. Sabatini and A. Vacca, J. Chem. Soc., Dalton Trans.,
1985, 1195.
Acknowledgements
9 G. Gran, Analyst (London), 1952, 77, 661; F. J. Rossotti, J. Chem.
We thank the Dirección General de Investigación Científica y
Técnica (PB95-1121-C02-01 and PB95-1121-C02-02) for
support. E. Monrabal is grateful to the Generalitat Valenciana
for a predoctoral fellowship.
Educ., 1965, 42, 375.
10 M. Costero, C. Andreu, M. Pitarch and R. Andreu, Tetrahedron,
1996, 52, 3683.
11 G. M. Sheldrick, SHELXS97, Program for structure solution,
University of Göttingen, 1990.
12 G. M. Sheldrick, SHELXL98, Program for refinement of crystal
structures, University of Göttingen, 1997.
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