Ferrocene-based small molecules for dual-channel sensing of heavy- and transition-metal cations

Article abstract of DOI:10.1021/jo800709v

(Chemical Equation Presented) The synthesis, electrochemical, optical, and cation-sensing properties of ferrocene-pentakis(phenylthio)benzene dyads, linked through a putative cation-binding 2-azadiene bridge, are presented. Dyad 5 behaves as a highly selective dual-redox and chromogenic chemosensor molecule for Pb²⁺ cations; the oxidation redox peak is anodically shifted (ΔE_1/2 = 125 mV), and the low energy band of the absorption spectrum is red-shifted (Δλ = 119 nm) upon complexation with this metal cation. Linear sweep voltammetry and spectroelectrochemical studies revealed that Cu²⁺ and Hg²⁺ metal cations induced oxidation of the ferrocene unit. The isomeric dyad 7, in which the nitrogen atom and the ferrocene unit are in closer proximity, has shown its ability for sensing both Pb²⁺ and Hg²⁺ ions; the oxidation redox peak is anodically higher shifted (ΔE_1/2 = 340 mV), and the low energy band of the absorption spectrum is lower red-shifted (Δλ = 61 nm) that those found for dyad 5. The changes in the absorption spectra are accompanied by dramatic color changes which allow the potential for naked eye detection. A further exciting property of dyad 7 is that it behaves as an electrochemically induced switchable chemosensor for Pb²⁺ and Hg²⁺ because of the low metal-ion affinity of the oxidized 7 ^?+ species for these metal cations. The experimental data and conclusions about the ion-sensing properties are supported by DFT calculations.

Full text of DOI:10.1021/jo800709v

Ferrocene-Based Small Molecules for Dual-Channel Sensing of
Heavy- and Transition-Metal Cations
Antonio Caballero, Arturo Espinosa, Alberto Ta´rraga,* and Pedro Molina*
Departamento de Qu´ımica Orga´nica, Facultad de Qu´ımica, UniVersidad de Murcia,
Campus de Espinardo, E-30100 Murcia, Spain
pmolina@um.es; atarraga@um.es
ReceiVed March 31, 2008
Thesynthesis,electrochemical,optical,andcation-sensingpropertiesofferrocene-pentakis(phenylthio)benzene
dyads, linked through a putative cation-binding 2-azadiene bridge, are presented. Dyad 5 behaves as a
highly selective dual-redox and chromogenic chemosensor molecule for Pb2+ cations; the oxidation redox
peak is anodically shifted (∆E1/2 ) 125 mV), and the low energy band of the absorption spectrum is
red-shifted (∆λ ) 119 nm) upon complexation with this metal cation. Linear sweep voltammetry and
spectroelectrochemical studies revealed that Cu2+ and Hg2+ metal cations induced oxidation of the ferrocene
unit. The isomeric dyad 7, in which the nitrogen atom and the ferrocene unit are in closer proximity, has
shown its ability for sensing both Pb2+ and Hg2+ ions; the oxidation redox peak is anodically higher
shifted (∆E1/2 ) 340 mV), and the low energy band of the absorption spectrum is lower red-shifted (∆λ
) 61 nm) that those found for dyad 5. The changes in the absorption spectra are accompanied by dramatic
color changes which allow the potential for “naked eye” detection. A further exciting property of dyad
7 is that it behaves as an electrochemically induced switchable chemosensor for Pb2+ and Hg2+ because
of the low metal-ion affinity of the oxidized 7•+ species for these metal cations. The experimental data
and conclusions about the ion-sensing properties are supported by DFT calculations.
Introduction
cury that is even more toxic to aquatic organisms and birds
than inorganic mercury, which eventually reaches the top of
the food chain and accumulates in higher organisms, especially
in large edible fish.2 When consumed by humans, methylmer-
cury triggers several serious disorders including sensory, motor,
and neurological damage.3 The development of methods for the
determination mercury is, therefore, of significant importance
for environment and human health. In the past decade, research-
ers have done a big effort to develop new mercury sensors. An
The sensitive detection of heavy and transition-metal ions,
such as mercury(II) and lead(II), highly toxic environmental
pollutants arising from both natural and industrial sources, is
currently a task of prime importance for environmental or
biological applications. Mercury, one of the most toxic elements
in the world, represents a major toxicity to microorganism and
environment even in low concentrations. Inorganic mercury has
been reported to produce harmful effects at 5 mg/L in a culture
medium.1 Once introduced into the marine environment,
microorganisms convert it into methylmercury, a form of mer-
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10.1021/jo800709v CCC: $40.75
Published on Web 06/18/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 5489–5497 5489

Caballero et al.
important number of selective Hg2+ chemosensors having been
devised using redox,4 chromogenic,5 or fluorogenic6 changes
as detection channels.
subject, and only few molecule probes have been recently
described.4b,15
In order to improve both recognition and detection ability of
chemosensors for HTM, we turned our attention toward mo-
lecular systems combining multiple binding sites and a redox-
active signaling unit in one unique molecular material, with the
aim of achieving a new type of selective redox and chromogenic
molecular sensors. Ferrocene-based ligands have been found
to be useful for incorporating redox functions into supramo-
lecular complexes to bind and allow the electrochemical sensing
of cations, anions, and neutral molecules by change in the
oxidation potential of Fe(II)/Fe(III) redox couple.16 Due to the
special topology of the electron-acceptor group hexakis(phe-
nylthio)benzene (HPTB) and derivatives feature cavities with
selective inclusion behavior for several kinds of molecules.17
With these considerations in mind, we decided to combine the
redox activity of the ferrocene group and the binding ability of
the HPTB group. Thus, herein we describe the synthesis,
electrochemical, and sensing properties of the new ligands 5
and 7 in which a pentakis(phenylthio)phenyl subunit is linked
to a ferrocene unit through a 2-aza-1,3-butadiene bridge. The
multiresponsive character of the receptors and the ability of the
aza-bridge as well as the sulfur-rich aromatic ring to act as
favorable binding for cations in the recognition event are most
noteworthy.
In the same context, lead pollution is an ongoing danger to
the environment7 and human health, particularly in children
(memory loss, irritability, anemia, muscle paralysis, and mental
retardation).8 Thus, the level of this detrimental ion, which is
present in tap water as a result of dissolution from household
plumbing systems, is the object of several official norms. The
World Health Organization established in 1996 guidelines for
drinking water quality,9 which included a lead maximal value
of 10 mg L-1. Recently, considerable efforts have been
undertaken to develop fluorescent chemosensors for Pb2+ ions
based on peptide,10 protein,11 DNAzyme,12 polymer,13 and
small-molecule14 scaffolds.
There is, however, a paucity of use of multichannel receptors
as potential guest reporters via multiple signaling patterns.
Specifically, the development of multichannel Hg2+- and Pb2+
-
selective chemosensors is, as far as we know, an unexplored
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Results and Discussion
Synthesis. The preparation of the ferrocene derivatives 5 and
7 is outlined in Schemes 1 and 2. Specifically, the isomer 5
bearing the metallocene unit linked to the 4 position of the
2-azadiene bridge was prepared starting from the appropriate
N-substituted diethylaminophosphonate 3, which was obtained
in almost quantitative yield by condensation of aminometh-
ylphosphonate 2 with pentakis(phenylthio)benzaldehyde 1,
available from the reaction of pentafluorobenzaldehyde with
thiophenyl sodium salt in 1,3-dimethylimidazolidin-2-one.18
Treatment of 3 with n-BuLi at -78 °C and subsequent reaction
of the resulting metalloylide with formyl ferrocene 4 provided
5 in 75% yield (Scheme 1).
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5490 J. Org. Chem. Vol. 73, No. 14, 2008

Dual-Channel Sensing of HeaVy- and Transition-Metal Cations
SCHEME 1. Synthesis of Receptor 5a
SCHEME 3. Structure of the Intermediates Formed in the
HWE Reaction
TABLE 1. Calculateda Relative Gibbs Free Energiesb for the
Formation of Intermediate Compounds 8 in Model HWE Reactions
R1
R2
erythro
threo
8a
8b
8c
8d
8e
8f
Me
Ph
Me
Ph
-6.76
7.84
10.15
4.32
17.61
15.13
-8.79
3.53
6.81
-0.20
14.94
15.74
Ph
Fcc
Ph
Fcc
(PhS)5Ph
Ph
Ph
(PhS)5Ph
b
a CPCM(THF)/B3LYP/6-311G**//B3LYP/6-31G*. kcal·mol-1
.
c Fc )
a Reagents: (a) diethyl aminomethylphosphonate; (b) (i) n-BuLi/-78 °C,
(ii) formylferrocene.
ferrocenyl.
SCHEME 2. Synthesis of Receptor 7a
appeared as one singlet (-CHdN-) and two doublets
(-CHdCH-).
Assignment of the configuration of the double bonds present
in the 2-aza-1,3-butadiene bridge was achieved by inspection
of the corresponding 1H NMR spectroscopic data. It is generally
accepted that the stereoselectivity in HWE olefination reactions
is a result of both kinetic and thermodynamic control upon the
reversible formation of the erythro and threo adducts and their
decomposition to olefins. That is, the stereochemistry is
determined by a combination of the stereoselectivity in the initial
carbon-carbon bond-forming step and the reversibility of the
intermediate adducts. However, in general, this reaction pref-
erentially gives the more stable E-disubstituted olefins as a
consequence of the predominant formation of the thermody-
namically more stable threo adducts.20
The E-configuration of the carbon-carbon double bond in
compound 5, as is expected in this olefination process, was
confirmed by the value of the vicinal coupling constants (J )
13.0 Hz). In addition, NOE and two-dimensional NOESY
experiments carried out on CDCl3 solutions confirmed the (E,E)-
configuration of the double bonds present in the bridge of this
derivative.
a Reagents: (a) n-BuLi/-78 °C.
By contrast, formation of a carbon-carbon double bond in
compound 7, under the same reaction conditions, takes place
with Z-stereoselectivity as it was confirmed by analyzing the
coupling constants corresponding to the vinyl proton signals (J
) 7.80 Hz). In order to explain this unexpected Z-selective HWE
reaction, a computational study at the DFT level of the
intermediate erythro and threo adducts has been carried out.
With the aim of correctly grasping the origin of the Z-selectivity,
six model HWE reactions have been considered according to
Scheme 3. The computed changes in Gibbs free energy for the
formation of intermediates 8erythro and 8threo are collected in
Table 1.
Following the same Horner-Wadsworth-Emmons (HWE)
methodology, the isomeric derivative 7 was also prepared. Thus,
starting from diethyl [(ferrocenylmethylidene)aminome-
thyl]phosphonate 619 and 1, as carbonyl component, the isomer
7, with the structural feature of having the ferrocene unit linked
to the 1 position of the 2-azadiene bridge, was obtained in 67%
yield (Scheme 2).
Both 2-aza-1,3-butadiene derivatives 5 and 7 were fully
characterized using 1H and 13C NMR and FAB mass spectrom-
1
etry. In general, the H NMR spectra showed the appearance
of two pseudotriplets, integrating two protons each, assigned
to the four protons within the monosubstituted cyclopentadienyl
(Cp) ring and one singlet corresponding to the unsubstituted
Cp ring. The protons present in the 2-aza-1,3-butadiene bridge
In the simplest derivative with the smallest substituent,
formation of both diastereomeric pairs 8a is exergonic, with
(20) (a) Maryanoff, B. E.; Reitz, A. B. Chem. ReV. 1989, 89, 863–927, and
references cited therein. (b) Ando, K. J. Org. Chem. 1997, 62, 1934–1939. (c)
Ando, K. J. Org. Chem. 1998, 63, 8411–8416. (d) Wang, Y.; West, F. G.
Synthesis 2002, 99–103.
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Wurst, K.; Evans, D. J.; Vidal-Gancedo, J.; Rovira, C.; Molina, P.; Veciana, J.
Eur. J. Inorg. Chem. 2005, 2436–2450.
J. Org. Chem. Vol. 73, No. 14, 2008 5491

Caballero et al.
the Supporting Information) but in this case the R1 substituent
is oriented moving away from the bulky R2 group, therefore
lacking the subtle aromatic stabilizing interaction.
Electrochemical and Optical Properties. The redox chem-
istry of compounds 5 and 7 was investigated by linear sweep
voltammetry (LSV), cyclic voltammetry (CV), and Osteryoung
square wave voltammetry (OSWV) in a CH3CN solution
containing 0.15 M [n-Bu4N]ClO4 (TBAP)24 as supporting
electrolyte. Each receptor exhibited in the range 0-1.0 V a
reversible one-electron redox wave, typical of a ferrocene
derivative, at the half-wave potential value of E1/2 ) 0.590 V
and E1/2 ) 0.670 V versus decamethylferrocene (DMFc), for 5
and 7, respectively. The criteria applied for reversibility was a
separation of 60 mV between cathodic and anodic peaks, a ratio
of 1.0 ( 0.1 for the intensities of the cathodic and anodic
currents Ic/Ia, and no shift of the half-wave potentials with
varying scan rates. From these data, it is clear that the oxidation
potentials of the ferrocenyl units are strongly dependent on the
position of the 2-azadiene bridge to which they are attached,
the oxidation being easier when the ferrocene is linked to the 4
position of the bridge than when it is linked to the 1 position.
These derivatives could also show electroactivity due to the
presence of the oxidizable 2-aza-1,3-butadiene bridge in their
structures. However, upon scanning to higher potential (0-1.5
V), only compound 5 shows a clearly irreversible oxidation
wave at Epa ) 1.23 V vs DMFc, which was attributed to the
aza-bridge oxidation, whereas for compound 7 this wave was
silent. Moreover, when the voltammetric study was carried out
from -2 to +1 V, an additional irreversible wave appeared at
Epa ) 1.52 V and Epa ) 1.31 V for 5 and 7, respectively,
associated with the reduction process of the pentakis(phenylthio)
platform.
FIGURE 1. Calculated structure for the 8ferythro intermediate viewed
along the axis containing the newly formed C3-C4 bond of the
2-azadiene framework. Unrelevant H atoms are omitted for clarity.
the threo pair being more stable than the erythro one (∆Ge/t
THF
) - 2.03 kcal ·mol-1). A similar tendency (∆Ge/tTHF ) - 4.31
kcal/mol) is observed when two phenyl substituents are present
in 8b, although in this case, formation of both stereoisomers is
endergonic. Substitution of the phenyl R2 group in 8c or the R1
by a ferrocenyl unit in 8d, as in 5 and 7, respectively, does not
alter the above-mentioned higher stabilities of the threo over
the erythro forms (∆Ge/t
) -3.34 and -4.52 kcal ·mol-1
THF
for 8c and 8d, respectively), in agreement with the experimen-
tally observed E-selectivity in the HWE synthesis of several
previously reported 1-aryl-4-ferrocenyl-, 4-aryl-1-ferrocenyl-,
or even 1,4-diferrocenyl-2-aza-1,3-butadienes19,21 or their ru-
thenocenyl analogues.22 Coming back again to the diphenyl
derivative, if the R1 substituent on the phosphonate component
is changed by the more sterically demanding pentakis(phenylth-
io)phenyl group, the relative difference between the erythro and
The UV-vis data obtained in CH3CN for compounds 5 and
7 are consistent with most ferrocenyl chromophores in that they
exhibit two charge-transfer bands in the UV-vis region.25 These
spectra contain a prominent absorption band with a maximum
at 318 nm (ꢀ ) 30340 M-1 cm-1) and 316 nm (ꢀ ) 24100
M-1 cm-1) for 5 and 7, respectively, which can safely be
ascribed to a high energy ligand-centered π-π* electronic
transition (L-π*) (HE band). In addition to this band, another
threo isomers of 8e is rougthly maintained (∆Ge/t
) -2.67
THF
kcal kcal ·mol-1), and therefore, the E-azadiene is expected to
be preferentially formed via the more stable threo intermediate.
We believe that the same holds true if the phenyl substituent is
replaced by a ferrocenyl one, as in the reaction leading to
compound 5. On the contrary, when the bulkiest substituent
comes from the carbonyl component, the situation is reversed
as far as it is the only case in which the erythro intermediate,
precursor of the Z olefin, is more stable than the threo isomer
weaker absorption is visible at 484 nm (ꢀ ) 2798 M-1 cm-1
)
and 475 nm (ꢀ ) 1592 M-1 cm-1) for 5 and 7, respectively,
which is assigned to another localized excitation with a lower
energy produced either by two nearly degenerate transitions,
an Fe(II) d-d transition26 or by a metal-ligand charge transfer
(MLCT) process (dπ-π*) (LE band). This assignment is in
accordance with the latest theoretical treatment (model III)
reported by Barlow et al.27 Such spectral characteristics confer
an orange color to these species.
(∆Ge/t
) + 0.61 kcal·mol-1). Again, we assume the same
THF
behavior for the intermediates leading to compound 7. The
calculated structure for one of the erythro stereoisomers of 8f
is shown in Figure 1, with the numeration as sketched in Scheme
3. The most stable conformation is fixed by one strong hydrogen
bridge bond between a phosphonate terminal O atom and an
ortho H atom (dPO· · · H ) 2.105 Å, WBI 0.013; angle O · · ·H-C
158.8°) belonging to a phenylthio group in R2. The other
substituent R1 is then oriented approaching R2, whereby an
stabilizing aromatic edge-to-face interaction, close to the limiting
edge-tilted-T-type,23 is originated. A similar P-O· · ·H interac-
tion fixes the most stable conformation in the threo isomer (see
Metal-Ion Sensing Properties. One of the most interesting
attributes of ligands 5 and 7 is the presence of a redox-active
(23) (a) Hunter, C. A. Chem. Soc. ReV. 1994, 101–109. (b) Hobza, P.; Selzle,
H. L.; Schlag, E. W. Chem. ReV. 1994, 94, 1767–1785. (c) Hobza, P.; Havlas,
Z. Chem. ReV. 2000, 100, 4253–4264. (d) Jennings, W. B.; Farrell, B. M.; Malone,
J. F. Acc. Chem. Res. 2001, 34, 885–894.
(24) Warning! Perchlorate salts are hazardous because of the possibility of
explosion. Only small amounts of this material should be handled and with great
caution.
(21) (a) Caballero, A.; Tormos, R.; Espinosa, A.; Velasco, M. D.; Ta´rraga,
A.; Miranda, M. A.; Molina, P. Org. Lett. 2004, 6, 4599–4602. (b) Caballero,
A.; Ta´rraga, A.; Velasco, M. D.; Espinosa, A.; Molina, P. Org. Lett. 2005, 7,
3171–3174. (c) Caballero, A.; Espinosa, A.; Ta´rraga, A.; Molina, P. J. Org.
Chem. 2007, 72, 6924–6937. (d) Zapata, F.; Caballero, A.; Espinosa, A.; Ta´rraga,
A.; Molina, P. Org. Lett. 2007, 9, 2385–2388.
(25) Farrel, T.; Meyer-Friedrichsen, T.; Malessa, M.; Haase, D.; Saak, W.;
Asselberghs, I.; Wostyn, K.; Clays, K.; Persoons, A.; Heck, J.; Manning, A. R.
J. Chem. Soc., Dalton Trans. 2001, 29–36, and references cited therein.
(26) (a) Sohn, Y. S.; Hendrickson, D. N.; Gray, M. B. J. Am. Chem. Soc.
1971, 93, 3603–3619. (b) Sanderson, C. T.; Quinian, J. A.; Conover, R. C.;
Johnson, M. K.; Murphy, M.; Dluhy, R. A.; Kuntal, C. Inorg. Chem. 2005, 44,
3283–3289. (c) Gao, L.-B.; Zhang, L.-Y.; Shi, L.-X.; Cheng, Z.-N. Organome-
tallics 2005, 24, 1678–1684.
(22) Caballero, A.; Garc´ıa, R.; Espinosa, A.; Ta´rraga, A.; Molina, P. J. Org.
Chem. 2007, 72, 1161–1173.
5492 J. Org. Chem. Vol. 73, No. 14, 2008

Dual-Channel Sensing of HeaVy- and Transition-Metal Cations
FIGURE 3. Changes in the linear sweep voltammogram of 5 (1 ×
10-3 M) in CH3CN with TBAP (0.1 M) as supporting electrolyte,
obtained using a rotating disk electrode at 100 mV·s-1 and 1000 rpm,
when metal cations are added: (a) upon addition of increasing amounts
of Pb2+ cations and (b) upon addition of increasing amount of Hg2+
cations. Decamethylferrocene was used as an internal standard.
FIGURE 2. Evolution of the CV (a) and OSWV (b) of 5 (1 × 10-3
M) in CH3CN with TBAP (0.1 M) as supporting electrolyte scanned
at 0.1 V·s-1 from -0.7 to 1.0 V when Pb(ClO4)2 is added: from 0
(solid line) to 1 equiv (dashed line). Decamethylferrocene was used as
an internal standard.
ferrocene moiety close to the cation-binding nitrogen atom
within the bridge. Thus, metal recognition properties of these
ligands were evaluated by electrochemical, optical, and 1H NMR
techniques.
potentials, which is in agreement with the complexation process
previously observed by OSWV (Figure 3). Interestingly, addition
of Pb2+ ions also caused an anodic shift (∆Epa ) 202 mV) in
the wave associated to the pentakis(phenylthio) unit (see the
Supporting Information).
At first, their electrochemical behavior was investigated in
the presence of several metal cations such as Li+, Na+, K+,
Ca2+, Mg2+, Cu2+, Zn2+, Cd2+, Hg2+, Ni2+, and Pb2+ as their
perchlorate salts. Titration studies with addition of the above-
mentioned set of metal cations to an electrochemical solution
of receptor 5 (c ) 10-3 M) in CH3CN containing TBAP (0.1
M) as supporting electrolyte, demonstrate that while addition
of Cu2+, Hg2+ and Pb2+ ions promotes remarkable responses,
addition of Li+, Na+, K+, Ca2+, Mg2+, Zn2+, Cd2+, and Ni2+
metal ions had no effect either on LSV or on the CV or OSWV
of this receptor, even when present in a large excess. The results
obtained on the stepwise addition of substoichiometric amounts
of Pb2+ revealed the appearance, in the OSWV, of a new
oxidation peak at a more positive potential (E1/2 ) 0.715 V)
(∆E1/2 ) 0.125 V) associated with the formation of a complexed
species. The current intensity of this new peak increases until
1 equiv of the guest cation is added. At this point, the peak
corresponding to the uncomplexed receptor 5 disappears (Figure
2). The positive potential shift (∆E1/2 ) 0.125 V) observed for
the Fe(II)/Fe(III) redox wave upon complexation by Pb2+ cations
can be due to electrostatic repulsion effect between the bound
metal cation and the electrogenerated positive charge on the
oxidized ferrocenyl subunit. This leads to a decrease of the
association constant with the oxidized ligand and to a destabi-
lization of the complex. Thus, ∆E1/2 reflects the balance of the
interaction of the metal cation between the neutral and the
oxidized charged ligand.
Similar studies developed using the receptor 7, under the same
electrochemical conditions, demonstrate that while addition of
Hg2+ and Pb2+ ions promotes the formation of the corresponding
complexes, addition of Cu2+ induces the oxidation of the
ferrocene moiety present in this receptor. Moreover, addition
of Li+, Na+, K+, Ca2+, Mg2+, Zn2+, Cd2+, and Ni2+ metal ions
had no effect on the corresponding voltammograms (LSV, DPV
or OSWV). In fact, addition of increasing amounts of Hg2+ and
Pb2+ ions caused a progressive disappearance of the oxidation
peak present in the free receptor (E1/2 ) 0.670 V) and the
simultaneous appearance, in both cases, of a new oxidation wave
at E1/2 ) 1.010 V (∆E1/2 ) 0.340 V) whose current intensity
continuously increases, reaching its maximum when 1 equiv of
such metal cations is added (Figure 4). This particular behavior
is characteristic of a large equilibrium constant for the binding
of this cation by the neutral receptor.28 Upon addition of Pb2+
ions to receptor 7, a remarkable anodic shift (∆Epa ) 215 mV)
in the wave associated to the pentakis(phenylthio) unit was also
observed (see the Supporting Information).
This complexation process is also corroborated by using the
LSV technique, which showed a gradual positive shift of the
Fe(II)/Fe(III) redox couple until the formation of the corre-
sponding complexes is completed. On the other hand, the
interaction between ligand 7 and Cu2+ ions was also evaluated
by LSV, and it was verified that such interaction promotes the
oxidation of the free ligand, because upon addition of this metal
cation a gradual shift of the linear sweep voltammogran toward
cathodic currents was only observed (Figure 5).
Remarkably, LSV studies carried out upon addition of Cu2+
and Hg2+ to the CH3CN solution of this ligand showed a
significant shift of the sigmoidal voltammetric wave toward
cathodic currents, indicating that both metal cations promote
the oxidation of the free receptor. By contrast, the same
experiments carried out upon addition of Pb2+ revealed a shift
of the linear sweep voltammogram toward more positive
Moreover, the CV analysis of the complexes 7 · Hg2+ and
7·Pb2+ shows that their reduction processes take place at the
same reduction potential showed by the uncomplexed ligand 7,
which is indicative that the complex starts to be disrupted after
its electronic oxidation (Figure 4a). This behavior means that
(27) (a) Barlow, S.; Bunting, H. E.; Ringham, C.; Green, J. C.; Bublitz, G. U.;
Boxer, S. G.; Perry, J. W.; Marder, S. R. J. Am. Chem. Soc. 1999, 121, 3715–
3723. (b) Yamaguchi, Y.; Ding, W.; Sanderson, C. T.; Borden, M. L.; Morgan,
M. J.; Kutal, C. Coord. Chem. ReV. 2007, 251, 515–524.
(28) (a) Miller, S. R.; Gustowski, D. A.; Chen, Z. H.; Gokel, G. W.;
Echegoyen, L.; Kaifer, A. E. Anal. Chem. 1988, 60, 2021–2024. (b) Medina,
J. C.; Goodnow, T. T.; Rojas, M. T.; Atwood, J. L.; Kaifer, A. E.; Gokel, G. K.
J. Am. Chem. Soc. 1992, 114, 10583–10595.
J. Org. Chem. Vol. 73, No. 14, 2008 5493

Caballero et al.
TABLE 2. Relevant UV-vis/Near-IR Data of the Free Receptor,
Oxidized Species, and Receptor/Metal Complexes
compd
λmax (nm) (ꢀ (M-1cm-1))
5
318 (30340), 484 (2798)
325 (20660), 356 (sh), 603 (2726)
304 (28510), 848 (640)
304 (26000), 832 (360)
304 (28210), 855 (520)
316 (24100), 475 (1592)
323 (24087), 536 (2653)
311 (16435), 819 (125)
323 (24100), 536 (2690)
310 (16500), 852 (123)
5·Pb2+
5·Cu2+
5·Hg2+
a
5•+
7
7·Pb2+
7·Cu2+
7·Hg2+
a
7•+
a Oxidized species obtained electrochemically in CH2Cl2 (c ) 1 ×
10-3 M) using [n-Bu4N][PF6] (0.15 M) as supporting electrolyte.
FIGURE 4. Evolution of the CV (a) and OSWV (b) of 7 (1 × 10-3
M) in CH3CN with TBAP (0.1 M) as supporting electrolyte scanned
at 0.1 V ·s-1 when Pb(ClO4)2 is added from 0 (solid line) to 1 equiv
(dashed line). Decamethylferrocene was used as an internal standard.
FIGURE 6. (a) Changes in the absorption spectra of 5 (1 × 10-4 M)
in CH3CN upon addition of increasing amounts of Pb2+ (2.5 × 10-2
M) in CH3CN. (b) Job’s plot for 5 and Pb2+, indicating the formation
of a 1:1 complex. The total [5] + [Pb2+] ) 1 × 10-4 M (λabs ) 603
nm).
quantitatively.30 It is worth mentioning that no changes were
observed in the UV-vis spectra upon addition of Li+, Na+,
K+, Ca2+, Mg2+, Zn2+, Cd2+, and Ni2+ metal ions, even in a
large excess; however, significant modifications were observed
upon addition of Cu2+, Hg2+, and Pb2+ (Table 2).
FIGURE 5. Changes in the linear sweep voltammogram of 7 (1 ×
10-3 M) in CH3CN with TBAP (0.1 M) as supporting electrolyte,
obtained using a rotating disk electrode at 100 mV·s-1 and 1000 rpm,
when metal cations are added: (a) upon addition of increasing amounts
of Pb2+ cations and (b) upon addition of increasing amount of Cu2+
cations. Decamethylferrocene was used as an internal standard.
Thus, the addition of increasing amounts of Pb2+ ions to a
solution of 5 caused the disappearance of the LE band at λ )
484 nm along with a progressive appearance of a new band
located at λ ) 603 nm (ꢀ ) 2726 M-1 cm-1) as well as a
decrease of the initial HE band intensity. Three well-defined
isosbestic points at 356, 483, and 519 nm indicate that a neat
interconversion between the uncomplexed and complexed
species occurs. The new LE band is red-shifted by 119 nm and
is responsible for the change of color, from orange to deep green,
which can be used for a “naked-eye” detection of this metal
ion. Binding assays using the method of continuous variations
(Job’s plot) (Figure 6) suggests a 1:1 binding model (metal/
ligand) with a log Ka ) 4.30 ( 0.15.
this receptor is not only able to monitor binding but it is also
able to behave as an electrochemically induced switchable
chemosensor for Pb2+ and Hg2+ through the progressive
electrochemical release of these metal cations; that is, the
binding constant upon electrochemical oxidation is decreased.
Previous studies on ferrocene-based ligands have shown that
their characteristic low energy (LE) bands in the absorption
spectra are perturbed upon complexation.29 Therefore, the metal
recognition properties of the ligands 5 and 7 toward metal ions
were also evaluated by UV-vis spectroscopy. Titration experi-
ments for CH3CN solutions of these ligands (c ) 1 × 10-4 M),
and the corresponding ions were performed and analyzed
By contrast, addition of Cu2+ and Hg2+ metal ions to a
solution of 5 produces the same perturbations in its absorption
(30) Specfit/32 Global Analysis System, 1999-2004, Spectrum Software
Associates (SpecSoft@compuserve.com). The Specfit program was aquired from
Bio-logic, SA (www.bio-logic.info) in January 2005. The equation to be adjusted
by nonlinear regression using the above-mentioned software was ∆A/b )
{K11∆ꢀHG[H]tot[G]}/{1 + K11[G]}, where H ) host, G ) guest, HG ) complex,
∆A ) variation in the absorption, b ) cell width, K11 ) association constant for
a 1:1 model, and ∆ꢀHG ) variation of molar absorptivity.
(29) (a) Marder, S. R.; Perry, J. W.; Tiemann, B. G. Organometallics 1991,
10, 1896–1901. (b) Coe, B. J.; Jones, C. J.; McCleverty, J. A.; Bloor, D.; Cross,
G. J. J. Organomet. Chem. 1994, 464, 225–232. (c) Mu¨ller, T. J.; Netz, A.;
Ansorge, M. Organometallics 1999, 18, 5066–5074. (d) Carr, J. D.; Coles, S. J.;
Asan, M. B.; Hurthouse4, M. B.; Malik, K. M. A.; Tucker, J. H. R. J. Chem.
Soc., Dalton Trans. 1999, 57–62.
5494 J. Org. Chem. Vol. 73, No. 14, 2008

Dual-Channel Sensing of HeaVy- and Transition-Metal Cations
For the reported constants to be taken with confidence, we
have proved the reversibility of the complexation processes by
carrying out the following experimental test: 0.5 equiv of
Pb(ClO4)2 was added to a solution of the receptor 5 in CH2Cl2
to obtain the complexed 5·Pb2+, whose OSWV voltammogram
and UV/vis spectra were recorded. The CH2Cl2 solution of the
complex was washed several times with water until the color
of the solution changed from deep green to orange. The organic
layer was dried, and the optical spectrum, DPV voltammogram,
1
and H NMR spectrum were recorded and they were found to
be the same as that of the free receptor 5. Afterward, 0.5 equiv
FIGURE 7. 1H NMR spectral changes observed for receptor 7 in
CD3CN (a) and after addition of 1 equiv of Pb2+ (b).
of Pb(ClO4)2 was added to this solution, and the initial UV/vis
1
spectrum, DPV voltammogram, and H NMR spectrum of the
complex 5·Pb2+ were fully recovered together with its deep
green color. This experiment was carried out over several cycles,
and the optical spectrum was recorded after each step, thus
demonstrating the high degree of reversibility of the complex-
ation/decomplexation process (see the Supporting Information).
Similar studies were carried out using the receptor 7 and the
adequate divalent metal cation (Pb2+ and Hg2+), which confirm
the reversibility of this process between this receptor and such
cationic metal species.
spectra as those observed when 5 was electrochemically oxidized
(Table 2): a new ligand-to-metal (LMCT) band at λ ≈ 800 nm
appears, with concomitant decreasing of the band appearing at
λ ) 584 nm.19
The stoichiometry of the complex has also been confirmed
by ESI-MS, where peaks at m/z 1062.3 [5·Pb]2+ and m/z 1161.9
[5·Pb·(ClO4)]+ are observed. Their relative abundance of the
isotopic clusters was in good agreement with the simulated
spectrum of the 1:1 complex.
Quantum Chemical Calculations. In order to get informa-
tion about the coordinating sites of receptors 5 and 7, DFT-
based quantum calculations have also been carried out. First of
all, the specific role of the pentakis(phenylthio)phenyl (PPTP)
group in the complexation event was separately evaluated by
considering the different posibilities of interaction between Hg2+
or Pb2+ perchlorates and hexakis(phenylthio)benzene (HPTB).
In agreement with the X-ray structures obtained for some
derivatives,31 HPTB itself shows a minimum-energy structure
featuring a regular alternance of phenylthio groups up and down
the central benzene ring, with overall quasi-S6 symmetry,
characterized by dihedral angles of 62.9° and 47.4° around the
bonds between the S atoms and the central and terminal aromatic
rings, respectively. This pattern in the free receptor forms two
cavities whose size is determined by the closest H · · ·H distance
of 3.540 Å between inner ortho H atoms of the phenyl side
arms. The complexation of M(ClO4)2 salts (M ) Pb, Hg) by
HPTB occurs with the latter acting as heteroditopic receptor
In comparison to the above-mentioned results obtained with
ligand 5, the titration studies of ligand 7 toward the same set of
metal cations and under the same conditions revealed a different
behavior than 5 upon addition of Cu2+, Hg2+, and Pb2+. In this
case, whereas Hg2+ and Pb2+ promote a clear complexation
process, Cu2+ induces again the oxidation of the receptor, which
is confirmed by comparison of the absorption spectrum resulting
from the electrochemical oxidation of 7 and that obtained upon
addition of Cu2+ metal ions (Table 2). It is worth mentioning
that addition of Hg2+ and Pb2+ elicited the same optical
response. In both cases, addition of such divalent metal cations
to 7 induced a red shift of the LE band from 475 to 536 nm
(∆λ ) 61 nm) with simultaneous change in the color of the
solution from orange to deep blue. In these cases, 1:1 binding
models were also observed and the corresponding binding
constants were also determined by the analysis of the spectral
titration data by using the already mentioned software (log Ka
) 5.37 ( 0.21 for Hg2+ and log Ka ) 5.34 ( 0.18 for Pb2+).
for the M(ClO4)+ cation and the ClO4 anion at every side of
-
To support the results obtained by electrochemical and
UV-vis experiments, and in order to obtain additional informa-
tion about the coordination of these metal cations by ligands 5
and 7, we also performed a 1H NMR spectroscopic analysis. In
both cases, the most significant changes observed during the
titration experiments are as follows (see the Supporting Infor-
mation): (1) the iminic proton shifts to downfield: ∆δ ) 0.04
ppm for 5 and ∆δ ) 0.27 ppm for 7; (2) whereas the two well-
separated doublets due to the ethylenic protons, N-CHdCH
and N-CHdCH, within the aza-bridge are clearly upfield-
shifted in the case of 7 (∆δ ) - 0.67 ppm and ∆δ ) -0.57
ppm), and in 5 the corresponding protons are slightly upfield
(∆δ ) - 0.04 ppm) and downfield (∆δ ) 0.15 ppm) shifted,
respectively; (3) the R- and ꢀ-protons within the monosubstituted
the molecule. Formation of the corresponding (ClO4) ·
HPTB·M(ClO4) complexes resulted from slightly endergonic
processes in both cases (∆G°compl ) 8.79 and 10.40 kcal ·mol-1
for M ) Pb and Hg, respectively) (see below) under the working
level of theory. Binding of a Pb(ClO4)+ cation by HPTB is
slightly exergonic (∆G°compl ) -2.65 kcal·mol-1) and preor-
ganizes the other half of the receptor for hosting a ClO4- anion
with very little modification (Lstrain ) 0.51 kcal · mol-1).
Conversely, complexation by HPTB of a Hg(ClO4)+ unit has
been found to be highly unstable (∆G°compl ) 64.27
kcal·mol-1), and instead, separated interaction with Hg2+ and
ClO4- ions is preferred (∆G°compl ) 26.86 kcal ·mol-1) although
still considerably endergonic.
Among several local minima, the lowest energy geometries
for the compounds derived from the complexation of azadienes
5 and 7 with M(ClO4)2 salts (M ) Pb, Hg) were those obtained
from the above (ClO4)·HPTB·M(ClO4) complexes upon sub-
stitution of one phenylthio sidearm by the appropriate ferrocenyl-
Cp ring of the ferrocene units are downfield shifted: ∆δHR
)
0.08 and 0.32 and ∆δHꢀ ) 0.18 and 0.11, for 5 and 7,
respectively; (4) the singlet corresponding to the five protons
of the unsubstituted Cp ring of the ferrocene moiety is also
downshifted in both cases: ∆δ ) 0.04 ppm and ∆δ ) 0.11
ppm for 5 and 7, respectively (Figure 7). From the magnitude
of these observed shifts, it can be surmised that the coordination
exerts a more powerful effect on the ligand 7 than in 5.
(31) (a) MacNicol, D. D.; Wilson, D. R. J. Chem. Soc., Chem. Commun.
1976, 494. (b) MacNicol, D. D. In Inclusion Compounds; Atwood, J. L., Davies,
J. E. D., MacNicol, D. D., Eds.; Academic Press: London, 1984; Vol. 2, Chapter
5.
J. Org. Chem. Vol. 73, No. 14, 2008 5495

Caballero et al.
TABLE 3. Selected Electronic, Structural, and Thermodynamic
Parameters for the Calculated Structures of Receptors 5 and 7 and
Their Complexes with Pb(ClO4)2 and Hg(ClO4)2
a
b
c
c
QFc
dFe-Cpb
∆Gcompl
Lstrain
FcH•+
5
5·Pb(ClO4)2
5·Hg(ClO4)2
7
0.745
0.008
0.068
0.847
0.051
0.141
0.141
2.27
0.17
0.52
6.50
0.25
0.99
1.00
1.66
-48.90
11.71
18.24
7·Pb(ClO4)2
7·Hg(ClO4)2
-2.85
-15.63
7.76
6.36
a Total natural charge (au) along the ferrocenyl unit. b Distance
between Fe and Cp centroid for the unsubstituted ring (Cpb), referenced
to that calculated for parent ferrocene, 1.654 Å (Å × 10-2). c Free
energies in CH3CN solution (kcal ·mol-1).
energy is mainly due to the internal redox process, as evidenced
by the analogous reaction in the model system HPTB, as far as
the initial formation of (ClO4)·HPTB·Hg(ClO4) is endergonic
(see before) but in the presence of ferrocene the intermolecular
redox process to give HPTB ·Hg(ClO4) and FcH ·(ClO4) is
considerably exergonic (∆G°redox ) -50.11 kcal ·mol-1).
For receptor 7 calculations predict the same behavior for both
metal diperchlorates and internal redox processes were observed
in no case (Table 3), in agreement with the experimental
evidence. In the complex 7·Pb(ClO4)2 (Figure 8b), the Pb-
(ClO4)+ unit is located so as to allow the Pb2+ cation to complete
its coordination sphere with the N atom of the azadiene bridge
(dN· · · Pb ) 2.530 Å, WBI 0.229) one S atom at the PPTP group
(dS· · ·Pb ) 2.909 Å, WBI 0.339) and a phenyl substituent (closest
dC· · · Pb ) 3.521 Å, total WBIPh-Pb 0.084). Again, the second
perchlorate unit is located at the other side of the PPTP group
and interacting with the ortho and meta H atoms of three phenyl
groups. The structure of 7·Hg(ClO4)2 (see the Supporting
Information) very much resembles that of Pb2+, with analogous
bonding of Hg2+ to N (dN· · ·Hg ) 2.492 Å, WBI 0.035), S (dS· · ·Hg
) 2.496 Å, WBI 0.117), and phenyl (closest dC· · · Hg ) 3.020
Å, total WBIPh-Hg 0.020) donors.
FIGURE 8. (a) Calculated structure for complex 5·Pb(ClO4)2. Host
in capped sticks and guest highlighted in space-filling representation.
(b) Calculated structure for complex 7·Pb(ClO4)2. Host in capped sticks
and guest highlighted in space-filling representation.
azadiene moiety. Thus, in 5·Pb(ClO4)2 (Figure 8a) the coordi-
nation sphere around Pb2+ is completed by coordination with
the azadiene N atom (dN· · · Pb ) 2.463 Å, WBI 0.242) and two
phenyl rings that are positioned in virtually parallel planes at
both sides of the azadiene bidge (closest dC· · · Pb ) 3.058 and
3.098 Å, total WBIPh-Pb 0.173 and 0.166). The second per-
chlorate unit is located at the other side of the PPTP group and
interacting via hydrogen bridge bonds with H1 and H3 of the
2-azadiene bridge.
As expected, according to our calculations the complex
resulting from the reaction of 5 with Hg(ClO4)2 had a geometry
corresponding to the oxidized receptor 5·+ interacting with the
reduced Hg(I) perchlorate, as evidenced by the electronic and
structural features collected in Table 3, which nicely agree with
the above-mentioned experimental results. Specially relevant
is the total natural charge within the ferrocenyl unit, very much
higher than the residual values obtained for 5 or its complex
with Pb(ClO4)2. Furthermore we have recently found19 that the
distance between Fe atom and the centroid of the cyclopenta-
dienyl rings has diagnostig relevance for characterizing the
oxidation degree in ferrocene or ruthenocene derivatives, as far
as it results almost insensitive to the nature of electron donating
or withrawing substituents but is considerably increased in
radical-cation metallocinium species, probably because of the
removal of an electron which is slightly bonding with respect
to the metal-ring interaction. The large calculated complexation
Conclusion
The synthesis, electrochemical, optical, and cation sensing
properties of ferrocene-pentakis(phenylthio)benzene dyads,
linked through a putative cation binding 2-azadiene bridge, are
presented. The synthetic methodology for the preparation of the
1,4-disubstituted 2-aza-1,3-butadienes 5 and 7 is based on the
temporal condensation of the readily available aminometh-
ylphosphonate with the appropriate aldehyde followed by
metalation of the resulting phosphonate and subsequent reaction
with a different aldehyde. The substituent at position 1 arises
from the aldehyde used in the first step, whereas the substituent
at position 4 comes from the aldehyde used in the last step.
The binding events are strongly affected by the relative position
of the ferrocene with respect the nitrogen atom, indicating that
shorter distances between the nitrogen donor atom within the
bridge and the ferrocene unit correspond to smaller selectivity
in the recognition properties of the ligand. Dyad 5 behaves as
a highly selective dual redox and chromogenic chemosensor
for Pb2+ cations; the oxidation redox peak is anodically shifted
(∆E1/2 ) 125 mV) and its low-energy band of the absorption
spectrum is red-shifted (∆λ ) 119 nm), upon complexation with
this metal cation. Whereas, Cu2+ and Hg2+ metal cations
induced oxidation of the ferrocenyl-end group, which is
confirmed by spectroelectrochemical studies and linear sweep
5496 J. Org. Chem. Vol. 73, No. 14, 2008

Dual-Channel Sensing of HeaVy- and Transition-Metal Cations
N-substituted diethyl aminomethylphosphonate 3 or 6 (1.0 mmol)
in dry THF (15 mL) at -78 °C and under nitrogen atmosphere
was added n-BuLi 1.6 M in hexane (0.33 mL). Then, a solution of
the adequate aldehyde (1.0 mmol) in dry THF (10 mL) was slowly
added, and the mixture was stirred for 1.5 h. The reaction mixture
was allowed to reach the room temperature (30 min), and then
it was heated under reflux temperature overnight. After the solution
was cooled at 0 °C for 30 min, a precipitate was formed which
was filtered and washed with diethyl ether (2 × 10 mL) to give
the corresponding 1,4-disubstituted 2-aza-1,3-butadiene, which was
recrystallized from THF.
2-Aza-4-ferrocenyl-1-[pentakis(phenylthio)phenyl]-1,3-butadi-
ene 5. Yield: 75%. Mp: 165-166 °C. 1H NMR (400 MHz, CDCl3):
δ 4.20 (s, 5H), 4.33 (st, 2H), 4.40 (st, 2H), 6.90 (d, 1H, J ) 13.0
Hz), 6.91 (d, 1H, J ) 13.0 Hz,), 7.21-7.44 (m, 25H), 8.14 (s,
1H). 13C NMR (100 MHz, CDCl3): δ 67.3 (2 × CH), 69.4 (5 ×
CH), 69.5 (2 × CH), 80.8, 126.0, 126.1, 126.4, 128.0, 128.3, 128.7,
128.8, 128.9, 129.1, 131.5, 137.3, 137.6, 137.8, 138.3, 143.0, 146.0,
146.8, 148.8, 156.8. FAB MS: m/z (relative intensity): 856 (100,
M+ + 1). Anal. Calcd for C49H37FeNS5: C, 68.75; H, 4.36; N, 1.64.
Found: C, 68.60; H, 4.26; N, 1.75.
FIGURE 9. Changes in the color of ligand 5 (up) and 7 (down) upon
addition of the corresponding cation.
voltammetric (LSV) data. The isomeric dyad 7, in which the
nitrogen atom and the ferrocene unit are in closer proximity,
displays the same type of sensing properties toward Pb2+ and
Hg2+ ions; the oxidation redox peak is higher anodically shifted
(∆E1/2 ) 340 mV), and the low energy band of the absorption
spectrum is lower red-shifted (∆λ ) 61 nm) than those found
for dyad 5, whereas Cu2+ cations promote the oxidation of the
ferrocene unit. The changes in the absorption spectra are
accompanied by dramatic color changes, from orange to deep
green for receptor 5 and orange to deep blue for receptor 7,
which allow the potential for “naked eye” detection (Figure 9).
Moreover, dyad 7 also exhibited a selective Pb2+ and Hg2+
redox induced complexation/decomplexation type of signaling
patterns that can be used for the construction of more elaborate
supramolecular switching systems.
2-Aza-1-ferrocenyl-4-[pentakis(phenylthio)phenyl]-1,3-butadi-
1
ene 7. Yield: 67%. Mp: 60-61 °C. H NMR (400 MHz, CDCl3):
δ 4.18 (s, 5H), 4.47 (st, 2H), 4.56 (st, 2H), 6.63 (d, 1H, J ) 7.8
Hz), 6.89 (d, 1H, J ) 7.8 Hz,), 6.69-7.07 (m, 25H), 8.15 (s, 1H).
13C NMR (100 MHz, CDCl3): δ 69.1 (2 × CH), 69.5 (5 × CH),
71.1 (2 × CH), 81.1, 123.2, 125.4, 125.6, 126.0, 127.3, 127.5, 127.6,
127.7, 128.0, 128.6, 128.6, 138.4, 142.3, 144.1, 147.6, 148.9, 163.1.
FAB MS: m/z (relative intensity): 856 (100, M+ + 1). Anal. Calcd
for C49H37FeNS5: C, 68.75; H, 4.36; N, 1.64. Found: C, 68.87; H,
4.20; N, 1.80.
Experimental Section
Diethyl N-[Pentakis(phenylthio)]benzylidenaminomethylphos-
phonate, 3. To a mixture of diethyl aminomethylphosphonate (0.157
g, 0.93 mmol) and anhydrous Na2SO4 (10 g) in dry CH2Cl2 (30
mL) was added dropwise an equimolecular amount of pentak-
is(phenylthio)benzaldehyde 1 in CH2Cl2 (10 mL). The resulting
solution was stirred at room temperature for 2 h and then filtered.
From the filtrate, the solvent was removed under vacuum to give
the corresponding aminomethylphosphonate 3 in almost quantitative
yield, as a colorless oil which was used, without further purification,
Acknowledgment. We gratefully acknowledge the financial
support from Fundacio´n Se´neca (Agencia de Ciencia y Tecno-
log´ıa de la Regio´n de Murcia) projects 02970/PI/05 and 04509/
GERM/06 (Programa de Ayudas a Grupos de Excelencia de la
Regio´n de Murcia, Plan Regional de Ciencia y Tecnolog´ıa 2007/
2010). A.C. also thanks to Ministerio de Educacio´n y Ciencia
a predoctoral grant.
1
4
in the next step. H NMR (400 MHz, CDCl3): δ 1.14 (t, 6H, JH,P
2
) 7.2 Hz), 3.72 (d, 2H, JH,P ) 15.9 Hz), 3.94-3.99 (m, 4H),
6.82-7.10 (m, 25H), 7.97 (d, 1H,4JH,P ) 4.5 Hz). 13C NMR (100
3
1
Supporting Information Available: General comments;
computational details; NMR spectra, electrochemical, UV-vis,
MHz, CDCl3): δ 16.3 (d, JP,C ) 5.9 Hz), 56.9 (d, JP,C ) 154.3
2
Hz), 62.2 (d, JP,C ) 6.5 Hz), 126.0, 126.3, 128.1, 128.2, 128.2,
1
128.4, 128.7, 128.8, 129.0, 137.2, 137.4, 137.6, 141.8, 146.4, 147.5,
149.1, 164.2 (d, 3JP,C ) 18.3 Hz). 31P NMR (162.29 MHz, CDCl3):
δ 22.09. FAB MS: m/z (relative intensity): 796 (100, M+ + 1).
General Procedure for the Preparation of 1,4-Disubstituted
2-Aza-1,3-butadienes 5 and 7. To a solution of the appropriate
and H NMR titration experiments; reversibility experiments;
DFT-calculated structures. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO800709V
J. Org. Chem. Vol. 73, No. 14, 2008 5497