Control of peroxyoxalate chemiluminescence by nitrogen-containing ligand quenching: Turning off and on by ligand-metal ion host-guest interactions

Article abstract of DOI:10.1016/j.tet.2011.06.078

The control of peroxyoxalate chemiluminescence (PO-CL) by the coordination of nitrogen-containing ligands and metal cations was investigated. Turning the CL off and on was done by PO-CL using 15-monoazacrown-5-tethered anthracene and alkali metal ions. CL quenching and regeneration was also observed in the separated molecular system of 15-monoazacrown-5 and the fluorophores. CL quenching by a number of ligands bearing dipicolylamino groups was evaluated by these PO-CL reactions and found to be closely related to their oxidation potentials, which is dependent on the Weller rate law for electron exchange and this provides strong support for the existence of the CIEEL PO-CL process. When Zn²⁺ or Cu²⁺ are added to the PO-CL system quenched by the ligand, N-[2-(2,2′-dipicolylamino)ethyl]aniline, CL was turned on because the electron donating ability of the ligands was modulated. This was controlled by the coordination of the studied metal ions and, therefore, this system results in CL because of host-guest interactions.

Full text of DOI:10.1016/j.tet.2011.06.078

Tetrahedron 67 (2011) 6927e6933
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Control of peroxyoxalate chemiluminescence by nitrogen-containing ligand
quenching: turning off and on by ligandemetal ion hosteguest interactions
Takayuki Maruyama, Yasuyuki Fujie, Noriyuki Oya, Eisuke Hosaka, Aki Kanazawa, Daisuke Tanaka,
*
Yoshiyuki Hattori, Jiro Motoyoshiya
Division of Chemistry and Materials, Faculty of Textile Science and Technology, Shinshu University, Ueda, Nagano 386-8567, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 May 2011
Received in revised form 22 June 2011
Accepted 23 June 2011
Available online 30 June 2011
The control of peroxyoxalate chemiluminescence (PO-CL) by the coordination of nitrogen-containing
ligands and metal cations was investigated. Turning the CL off and on was done by PO-CL using 15-
monoazacrown-5-tethered anthracene and alkali metal ions. CL quenching and regeneration was also
observed in the separated molecular system of 15-monoazacrown-5 and the fluorophores. CL quenching
by a number of ligands bearing dipicolylamino groups was evaluated by these PO-CL reactions and found
to be closely related to their oxidation potentials, which is dependent on the Weller rate law for electron
exchange and this provides strong support for the existence of the CIEEL PO-CL process. When Zn2þ or
Cu2þ are added to the PO-CL system quenched by the ligand, N-[2-(2,20-dipicolylamino)ethyl]aniline, CL
was turned on because the electron donating ability of the ligands was modulated. This was controlled
by the coordination of the studied metal ions and, therefore, this system results in CL because of
hosteguest interactions.
Keywords:
Peroxyoxalate chemiluminescence
Quenching
CIEEL
Ligand
Dipicolylamino group
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
Chemiluminescence (CL) is becoming important in many
applications beyond chemical analyses, such as in biological
diagnostics, because an electric light source is not required to
decrease the background noise, which results in the detection of
light only from the fluorescent target species.1 Of all the CL re-
actions, peroxyoxalate chemiluminescence (PO-CL) that is gener-
ated from the reactions of active oxalates bearing phenol moieties
that contain electron withdrawing groups, such as bis(2,4,6-
trichlorophenyl) oxalate (TCPO) or bis(2,4-dinitrophenyl) oxalate
(DNPO) and alkaline hydrogen peroxide in the presence of various
fluorophores is the most effective (Scheme 1). An enormous
amount of effort has been put into mechanistic studies2 and into
analytical applications.3
A chemically initiated electron exchange luminescence (CIEEL)
process has been suggested to be a plausible explanation for the
chemiexcitation pathway during PO-CL (Scheme 2).4 In this process
the electron exchange between high energy intermediates (ac-
ceptors), 1,2-dioxetanones or 1,2-dioxetanedione, and fluorophores
(donors) is a crucial step. Based on this convincing mechanism we
hypothesize that if additives control the CIEEL process by an
Scheme 1. Peroxyoxalate chemiluminescence (PO-CL) reaction.
electronic interaction the CL might turn off and on under suitable
conditions. To turn the CL off, CL quenching should be dependent
on the electron donating ability of the organic additives and this
electron donor additive might interrupt the CIEEL process and
disrupt the electron exchange between the high energy in-
termediate and a fluorophore. Therefore, an electron donating ad-
ditive and a fluorophore would compete during their interaction
with the dioxetanones. The additive would, therefore, behave as
a CL quencher. When the additive is a nitrogen-containing ligand,
the complexation of a suitable metal ion to the ligand can control its
electron donating ability and the metal ion will become important
in switching the CL on. If this process operates in an intermolecular
manner there is a possibility that a good choice of a combination of
additives will enable the visualization of various molecular in-
teractions by the CL technique, as shown in Scheme 3.
* Corresponding author. Tel.: þ81 268 21 5402; fax: þ81 268 21 5391; e-mail
address: jmotoyo@shinshu-u.ac.jp (J. Motoyoshiya).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.078

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T. Maruyama et al. / Tetrahedron 67 (2011) 6927e6933
Scheme 2. A plausible CIEEL process during PO-CL.
Scheme 3. Concept of CL detection during hosteguest interactions.
In this paper, CL control by a hosteguest interaction during PO-
15-monoazacrown-5-tethered fluorescent molecules by interrupt-
ing PET fluorescence quenching.7 The fluorescence spectra of 1
were measured under various Naþ concentrations because the in-
teraction of 1 and Naþ has not been well documented. As shown in
Fig. 1, the fluorescence intensity increased markedly as the Naþ
concentration increased despite the required large excess of Naþ,
which led us to apply this event to the chemiluminescence system.
CL reactions was investigated using several nitrogen-containing
ligands. Efforts were directed toward finding a relationship be-
tween the electronic effect of the ligands and CL quenching during
the CIEEL process. This was applied to the CL detection of the
hosteguest interaction between the ligands and the metal ions.
This system resembles a displacement indicator assay,5 which is
a fluorescence detection method in which analyte binding leads to
indicator displacement to yield optical signal modulation. However,
this is the first time that such a noncovalent system has been used
in a CL reaction.
2. Results and discussion
2.1. CL control with azacrown ethers in an intra- and
intermolecular fashion
15-Monoazacrown-5-tethered anthracene (1) is a well-known
fluorescent compound6 capable of changing its fluorescence in-
tensity upon chelation by suitable metal ions and this fluorescence
modulation is due to the control of fluorescence quenching by
intramolecular photoinduced electron transfer (PET). When this
compound is used as a fluorophore in PO-CL the CL is also expected
to be controlled by the interaction with metal ions.
Fig. 1. Fluorescence spectra of 1 as a function of [NaClO4]. Compound [1]¼1.0ꢀ10ꢁ4
M
in THF.
Before the application of 1 to a chemiluminescence reaction, its
fluorescence behavior upon metal ion complexation was explored.
The ionophore 15-monoazacrown-5 can incorporate various alkali-
and alkaline earth metal ions and among them sodium and calcium
cations are most effective in increasing the fluorescence intensity of
Using 1 as a fluoroionophore the CL reaction was carried out
with several reagents including bis(4-chlorophenyl) oxalate (4-
CPO), hydrogen peroxide, and tetrabutylammonium hydroxide
(TBAH) as a metal free base. The reaction without any metal cation
in aqueous THF gave a weak CL emission, as expected from the

T. Maruyama et al. / Tetrahedron 67 (2011) 6927e6933
6929
fluorescence spectrum shown in Fig. 1. In contrast, the addition of
NaClO4 increased the CL quantum yield (FCL) 10 times compared to
the system without Naþ. Among the alkali metal ions tested in this
study, Naþ was the most effective in increasing the FCL, as shown in
Fig. 2, which is based on the advantageous incorporation of Naþ
into the azacrown cavity.7
a value 2.3 times higher than the system without Naþ while a FCL
value 100 times higher was obtained when coumarin-7 was used as
a fluorophore (Fig.3, inset). During CL quenching an electronic in-
teraction takes place between the ligands and the high energy in-
termediates rather than fluorescence quenching between the
ligands and the fluorophores by intermolecular PET because the
solutions containing the fluorophores and the azacrown do not give
significant fluorescence quenching even when using 100 times
more azacrown at which the CL emission from the PO-CL reaction
would be completely quenched. Thus, in this PO-CL reaction the
azacrown is an electron donor to the high energy peroxyoxalate
intermediates and it does not donate electrons to the electronically
excited fluorophores. The high energy intermediates, such as
dioxetanones act as electron acceptors to inhibit the chem-
iexcitation of the fluorophores resulting in CL quenching. This
process involves the CL turning off or on, and implies that the CL
can be controlled by the hosteguest interaction between the var-
ious ligands and metal ions.
2.2. Preparation and oxidation potentials of the ligands
Dipicolylamino groups are useful as chelators in fluorescence
chemosensors8 for the detection of biologically important metal
ions, because of their strong electron donating ability, as well as
their strong coordination of particular metal ions with excellent
selectivity. We applied this functionality containing multiple ni-
trogen atoms to the PO-CL system and its intensity was controlled
by the metal ioneligand interaction (vide infra). The ligands (2e4)
shown in Fig. 4 were prepared by a modification of the established
method8c,d,9 using the reactions of 2-(chloromethyl)pyridine and
the corresponding amines. To investigate the effect of these li-
gands on CL quenching their oxidation potentials (Eox) were
measured by cyclic voltammetry. As shown in Table 1, the Eox of
the ligands are dependent on their electronic nature as modulated
by the attached substituents for ligands 2aec and 3aec. The
electron donating substituents increase the electron releasing
ability, which leads to a lower Eox. Ligand 4 has the highest Eox
among all the ligands probably because of its radical cation that is
generated after the release of an electron, which causes it to be
less stable as a result of the lack of a directly linked aromatic ring
on the nitrogen atom.
Fig. 2. PO-CL for compound 1 and the alkali metal ions. Compound 1 (7.5ꢀ10ꢁ4 M), 4-
CPO (7.5ꢀ10ꢁ5 M), LiClO4, NaClO4, and KClO4 (7.5ꢀ10ꢁ3 M), H2O2 (7.5ꢀ10ꢁ3 M), and
TBAH (7.5ꢀ10ꢁ4 M) in H2O/THF (1:3).
It is noteworthy that turning the CL off or on could also be done
in an intermolecular fashion using molecules where a fluorophore
and an ionophore are not covalently linked, such as free anthracene
and 15-monoazacrown-5. Turning the CL off was done by adding
15-monoazacrown-5 to the CL system containing 4-CPO, TBAH,
hydrogen peroxide, and anthracene as a fluorophore. The CL in-
tensity decreased with an increase in the 15-monoazacrown-5
concentration and it finally disappeared when 50 equiv of aza-
crown ether was added to the oxalate (Fig. 3), and hence 15-
monoazacrown-5 acted as a CL quencher during this PO-CL re-
action. Upon the addition of NaClO4 to the non-luminescent PO-CL
system that was quenched by the azacrown, FCL recovered to
Fig. 4. Structures of the ligands used in this study.
Table 1
Oxidation potentials (Eox) of ligands 2, 3, and 4
Ligand
Eoxa (V)
2a
2b
2c
3a
3b
3c
4
0.66
0.70
0.45
0.35
0.87
0.23
0.93
Fig. 3. PO-CL quenching by 15-monoazacrown-5 and CL recovery by the addition of
coumarin-7 and Naþ (inset). 4-CPO (1.0ꢀ10ꢁ4 M), anthracene (1.0ꢀ10ꢁ3 M), 5-
monoazacrown-15 (0e1.0ꢀ10ꢁ1 M), H2O2 (1.2ꢀ10ꢁ1 M), TBAH (1.0ꢀ10ꢁ3 M) in H2O/
THF (1:3). Inset: A; 4-CPO (0.75ꢀ10ꢁ4 M), H2O2 (0.25ꢀ10ꢁ2 M), TBAH (0.25ꢀ10ꢁ4 M),
15-monoazacrown-5 (0.75ꢀ10ꢁ3 M), coumarin-7 (0.75ꢀ10ꢁ4 M). B; addition of NaClO4
(0.75ꢀ10ꢁ1 M).
a
The measurements were carried out in THF/H2O (1:1). The ligand concentration
was 0.01 M and the electrolyte was Bu4NClO4. Platinum working electrode, Ag/AgCl
reference electrode. Scan rate of 10 mV sꢁ1
.

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T. Maruyama et al. / Tetrahedron 67 (2011) 6927e6933
2.3. CL quenching by the ligands containing dipicolylamino
groups
To investigate the role of the series of ligands described above as
CL quenchers systematically, the effect of ligand 2a on PO-CL
quenching was studied. PO-CL reactions that included TCPO as an
oxalate, hydrogen peroxide, Na2CO3, four kinds of fluorophores, and
2a at various concentrations were carried out. As shown in Fig. 5,
the CL intensity in the presence of fluorophores, such as 9,10-
diphenylanthracene (DPA), perylene, rubrene, and coumarin-7
gradually decreased along with an increase in the amount of 2a.
The PO-CL intensity is known to depend on the electronic property
as well as the fluorescent properties of the fluorophores.2l,4,10
Therefore, the CL intensity decayed in different ways for each flu-
orophore, as shown Fig. 5. The CL was almost completely inhibited
when a large excess of 2a was added in all cases. It is important to
note that 2a might be superior to the fluorophores as an electron
donor because of its much lower oxidation potentials compared to
all the fluorophores used here (1.24, 0.96, 0.94, 1.11 (V) for DPA,
perylene, rubrene, and coumarin-7, respectively).
Fig. 6. Ratio of FCL decrease because of the addition of ligands 2a, 2b, 2c, 3a, and 3c
during PO-CL. 4-CPO (0.75ꢀ10ꢁ5 M), perylene (0.75ꢀ10ꢁ4 M), H2O2 (0.25ꢀ10ꢁ2 M),
and Bu4NOH (1.25ꢀ10ꢁ4 M) in THF/H2O (1:1) were used.
quantification.11 Independently, we applied the kinetics of the en-
hanced CL to the present ligand-induced CL quenching by
exploiting the elementary reaction of the CL quenching process
involving the interaction between the high energy intermediate
and the ligands. The obtained equation shown below resembles the
SterneVolmer equation, and it has a linear relationship between
the double reciprocals of FCL and [F],
À
Á
1=FCL ¼ 1=FrFF 1 þ kQ ½Lꢂ=kss½Fꢂ
(1)
where Fr and FF are the reaction yield and the fluorescence
quantum yield of the fluorophore, respectively. kss is the rate con-
stant for energy transfer from the high energy intermediate to the
fluorophores and kQ is a conditional CL quenching constant that is
estimated as a measure of the CL quenching ability of the ligands.
This equation indicates that the ligands behave as quenchers and
a plot of the ligand concentration [L] versus the reciprocal FCL
should give a straight line when using a constant [F]. In addition,
the slope kQ/FrFFkss[F] provides a relative kQ for each ligand. Using
various concentrations of 2aec and 3c and by keeping [F] constant
the FCLs of perylene-enhanced PO-CL from the reaction of 4-CPO
and alkaline hydrogen peroxide were determined. As shown in
Fig. 7, the plots of [L] and 1/FCL form straight lines, which implies
Fig. 5. CL quenching in the presence of 2a during PO-CL using various fluorophores.
TCPO (0.75ꢀ10ꢁ5 M), the fluorophore (0.75ꢀ10ꢁ4 M), H2O2 (0.25ꢀ10ꢁ2 M), and Na2CO3
(1.25ꢀ10ꢁ4 M) in THF/H2O (3:1) were used.
For a systematic CL quenching study of the CIEEL process, a series
of ligands (2aec, 3aec, and 4) were employed for the PO-CL re-
actions in the presence of 4-CPO and perylene as the common ox-
alate and fluorophore, respectively. Of the seven ligands investigated
2aec, 3a, and 3c quenched the CL but 3b and 4 were much less ef-
fective (Fig. 6). If the observed CL quenching involves an electronic
interaction and the ligands compete with the fluorophores during
the CIEEL process the effect of the ligands on CL quenching should be
closely related to their Eox. The CL ligand quenching trend agrees
with this relation because 3b and 4, with a higher Eox, are inferior to
the other ligands with a lower Eox during CL quenching.
During the enhanced (indirect) CL, with PO-CL being typical, the
high energy intermediates interact with the fluorophores to gen-
erate excited fluorophores resulting in CL emission from their
fluorescence process. The kinetics of this process have been well
established.2a The double reciprocals of FCL and the fluorophore
concentration [F] are correlated by a single straight line. On the
other hand, the SterneVolmer equation has been applied to metal
ion-induced CL quenching in a few cases with regards to their
Fig. 7. Plot of CL quenching according to Eq. 1. 4-CPO (0.75ꢀ10ꢁ5 M), perylene
(0.75ꢀ10ꢁ4 M), H2O2 (0.25ꢀ10ꢁ2 M), and Na2CO3 (5.0ꢀ10ꢁ5 M) in THF/H2O (1:1) were
used. R2¼0.975 for 3c, 0.979 for 2c, 0.992 for 2a, and 0.962 for 2b.

T. Maruyama et al. / Tetrahedron 67 (2011) 6927e6933
6931
that the ligands interact with the high energy intermediates in
a bimolecular manner and behave as CL quenchers during en-
hanced PO-CL. It is noteworthy that the linear relationship between
ln (rel kQ) and the Eox of the ligands is consistent with the Weller
rate law12 for electron exchange (Fig. 8), except for the weakly
fluorescent ligand 3a and the ligands 3b and 4, which were not
effective CL quenchers. These results provide evidence for the in-
volvement of an electron exchange process, the CIEEL process,
during PO-CL from a different point of view as has been reported
previously in the literature.4
with an ionic radius similar to Zn2þ also responded to 2a (Fig. 10).
Here, we show only a few examples of CL regeneration by hoste-
guest interactions and these results show that hosteguest in-
teractions can be determined using CL, as shown in Scheme 3.
Fig. 9. Turning CL on by the interaction between 2aec and Zn2þ. TCPO (1.0ꢀ10ꢁ4 M),
Na2CO3 (1.0ꢀ10ꢁ4 M), H2O2 (1.2ꢀ10ꢁ2 M), perylene (1.0ꢀ10ꢁ4 M), and ligands
(1.0ꢀ10ꢁ3 M) were used.
Fig. 8. Plot of ln (rel kQ) against the Eox of the ligands.
2.4. Turning CL on by the interaction between ligands and
metal cations
Because of the strong chelating effect of dipicolylamino
groups,13 ligands 2aec coordinate to suitable metal ions to modu-
late their electron donating ability, which affects the modulation of
the CL intensity of PO-CL. Since Zn2þ is known to coordinate with
the 2-(dipicolylamino)ethylamino ligand and this favorable com-
plexiation has been widely used for fluorescent chemosensors14
the Zn-salt was employed to turn CL on by its interaction with
2aec. As described before, these ligands quench the CL from the
PO-CL reactions in the presence of various fluorophores (Fig. 5 for
the TCPOePO-CL reaction). The effect of Zn2þ on CL regeneration
was examined using various Zn2þ concentrations. In the rubrene-
enhanced TCPOePO-CL reaction, FCL increased sharply at an
equivalent concentration between 2a and Zn2þ and at this point the
maximum CL was observed. The FCL recovered to 20% of its initial
value compared to the system without 2a and Zn2þ. The use of
perylene as a fluorophore instead of rubrene led to the regeneration
of CL at up to 56%, 44%, and 40% at the maximum points by the
coordination of 2a, 2b, and 2c with Zn2þ in 1:1 ratios (Fig. 9).
However, the much higher concentration of the Zn-salt decreased
the CL intensity probably because of a change in the pH of the so-
lutions, which unfortunately restricts the application of this system
to the quantification of Zn2þ. On the other hand, the effect of highly
fluorescent coumarin-7 in turning the CL on was studied using
a lower concentration of 2a (10ꢁ4 M), and 54% CL recovery was
obtained. Therefore, the metal ioneligand complexation between
these additives can be determined at 10ꢁ4 M by this CL system
when suitable conditions are used. Attempts to find the hosteguest
interaction between 2a and other metal ions were also made in the
presence of Liþ, Ca2þ, Mn2þ, Co2þ, and Cu2þ and we found that Cu2þ
Fig. 10. Metal ion selective turning on of CL. TCPO (0.75ꢀ10ꢁ5 M), perylene
(0.75ꢀ10ꢁ4 M), 2a (0.75ꢀ10ꢁ3 M), metal ion (0.75ꢀ10ꢁ3 M, LiClO4, Ca (ClO4)2, MnSO4,
CoSO4, CuSO4, ZnSO4), H2O2 (0.25ꢀ10ꢁ2 M), and Na2CO3 (0.25ꢀ10ꢁ4 M) in THF/H2O
(1:1) were used.
3. Conclusions
A new aspect of PO-CL reactions as a result of the combination of
various fluorophores, ligands bearing dipicolylamino groups, and
metal ions is demonstrated. The ligands act as CL quenchers by an
electronic effect, but the CL turns on in the presence of suitable
metal ions because of the control of the electronic effect by the
complexation of metal ions with the ligands. Strong evidence for
the CIEEL process was also found based on the relationship be-
tween the CL quenching and the oxidation potentials of the ligands.
With a good choice of ligands and fluorophores various combina-
tions are possible as long as well designed electron donating li-
gands that are suitable for target molecules are available, and an
investigation is currently underway in our laboratory.

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T. Maruyama et al. / Tetrahedron 67 (2011) 6927e6933
4. Experimental
2H), 8.54 (d, 2H); 13C NMR (100 MHz, CDCl3)
d 41.80, 53.26, 60.73,
113.22,117.34,122.50,123.54,129.53,136.84,149.04,149.53, 159.66;
HRMS (EI): calcd for C20H22N4: 318.1844. Found: 318.1846.
4.1. General
Melting points were determined using a hot stage microscope
apparatus and were uncorrected. 1H and 13C NMR spectra were
recorded on an FT-NMR spectrometer at 400 MHz and 100 MHz,
4.2.3. N-[2-(2,20-Dipicolylamino)ethyl]-p-chloroaniline (2b). N-
(Chlorophenyl)ethylenediamine was prepared in a similar manner
to the procedure described above using 2-bromoethylamine
hydrobromide (1.1 g, 5.4 mmol) and p-chloroaniline (3.4 g,
27 mmol). Yield: 81% (0.75 g) as a brown liquid; 1H NMR (400 MHz,
respectively. The chemical shifts (d
) of the 1H and 13C NMR spectra
are reported in parts per million downfield from TMS as an internal
standard or from the residual solvent peak. Coupling constants (J)
are reported in hertz. Fluorescence quantum yields were estimated
using 9,10-diphenylanthracene (FF¼0.91 in benzene) as a standard.
Chemiluminescence quantum yields (FCL) were measured by
a photon-counting method using a Hamamatsu Photonics R464
photomultiplier connected to a photon-counting unit (C3866) and
a photon-counting board M8784 according to a previously reported
procedure.2l Luminol chemiluminescence was used as a standard in
DMSO for the calibration of the photomultiplier tube. Compound
(1) was prepared by an established method according to the liter-
ature. TCPO and 4-CPO were prepared by reacting oxalyl chloride
and the corresponding phenols in the presence of triethylamine in
benzene and were used after recrystallization.
CDCl3) d 1.45 (br s, 3H), 2.95 (t, 2H), 3.15 (t, 2H), 6.55 (d, 2H), 7.11 (d,
2H). Compound 2b was prepared using 2-(chloromethyl)pyridine
hydrochloride (1.5 g, 9.2 mmol), N-(4-chlorophenyl)ethylenedi-
amine (0.75 g, 4.5 mmol), and triethylamine (4.5 g, 45 mmol) in
a similar manner to that described above by heating for 3 h at 80 ꢃC.
Yield: 43% (0.69 g) as a brown viscous liquid; mp 86e88 ꢃC; 1H NMR
(400 MHz, CDCl3)
J¼8.8 Hz, 2H,), 7.07 (d, J¼8.8 Hz, 2H), 7.11e7.19 (m, 2H), 7.38 (d, 2H),
7.61 (t, 2H), 8.55 (d, 2H); 13C NMR (100 MHz, CDCl3)
41.95, 53.00,
d 2.87 (t, 2H), 3.15 (t, 2H), 3.88 (s, 4H), 6.49 (d,
d
60.72, 114.22, 121.72, 122.54, 123.55, 129.29, 136.83, 147.68, 149.56,
159.55; HRMS (EI): calcd for C20H21ClN4: 352.1455. Found: 352.1468.
4.2.4. N-(2-(2,20-Dipicolylamino)ethyl)-p-anisidine (2c). N-(Meth-
oxyphenyl)ethylenediamine was prepared in a similar manner to
the procedure described above using 2-bromoethylamine hydro-
bromide (2.0 g, 9.9 mmol) and p-anisidine (4.0 g, 33 mmol). Yield:
4.2. Preparation of azacrown-tethered anthracene (1) and
ligands 2aec, 3aec, and 4
88% (1.4 g) as a brown solid; 1H NMR (400 MHz, CDCl3)
d 1.45 (br s,
4.2.1. N-(9-Anthylmethyl)monoaza-15-crown-5 (1). The reaction
between 9-bromomethylanthracene (1.23 g, 4.6 mmol), 15-
monoazacrown-5 (1.0 g, 4.6 mmol), and Na2CO3 (0.92 g,
8.7 mmol) was carried out in CH3CN by heating at 80 ꢃC for 20 h.
After filtration and concentrating the filtrate purification was car-
ried out by column chromatography (SiO2, ethyl acetate as an el-
uant) and compound 1 was obtained (0.58 g, 31%) as a viscous
3H), 2.94 (t, 2H), 3.14 (t, 2H), 3.75 (s, 3H), 6.61 (d, 2H), 6.78 (d, 2H).
Compound 2c was prepared from 2-(chloromethyl)pyridine hy-
drochloride (2.1 g, 12 mmol), N-(4-methoxyphenyl)ethylenedi-
amine (0.79 g, 4.7 mmol), and triethylamine (4.5 g, 45 mmol) in
a manner similar to that described above by heating for 3 h at 80 ꢃC.
Yield: 26% (0.77 g) as a brown viscous solid; mp 37e41 ꢃC; 1H NMR
(400 MHz, CDCl3)
6.55 (d, J¼8.9 Hz, 2H), 6.75 (d, J¼8.9 Hz, 2H), 7.11e7.16 (m, 2H), 7.42
(d, 2H), 7.61 (t, 2H), 8.54 (d, 2H); 13C NMR (100 MHz, CDCl3)
42.83,
d 2.87 (t, 2H), 3.14 (t, 2H), 3.73 (s, 3H), 3.88 (s, 4H),
yellowish oil. 1H NMR (400 MHz, CDCl3)
d 2.91 (t, 4H), 3.57e3.66
(m, 16H), 4.61 (s, 2H), 7.42e7.52 (m, 4H), 7.98 (d, 2H), 8.93 (s, 1H),
d
8.54 (d, 2H).
53.45, 56.26, 60.80, 114.50, 115.26, 122.45, 123.49, 136.79, 143.40,
149.54, 152.30, 159.73; HRMS (EI): calcd for C21H24N4O: 348.1950.
Found: 348.1984. Anal. Calcd for C21H24N4O: C 72.39, H 6.94, N
16.08. Found: C 72.04, H 6.79, N 15.89.
4.2.2. N-(2-(2,20-Dipicolylamino)ethyl)aniline (2a). A solution of 2-
bromoethylamine hydrobromide (1.1 g, 5.4 mmol) and aniline
(3.0 g, 32 mmol) in toluene (8 ml) was stirred for 1 day at 120 ꢃC
under an argon atmosphere and the precipitated product was
collected by filtration. The salt was then treated with a 20% aqueous
NaOH solution and extracted with dichloromethane. The organic
phase was dried over anhydrous Na2SO4. After the Na2SO4 was
filtered out and the solvent was distilled the crude product was
further purified by column chromatography on silica gel (eluant:
methanol) to afford N-phenylethylenediamine as a red-brown liq-
4.2.5. p-Bis(2,20-dipicolylamino)benzene (3a). This compound was
prepared from 2-(chloromethyl)pyridine hydrochloride (2.0 g,
12 mmol), p-phenylenediamine (0.26 g, 2.4 mmol), and triethyl-
amine (5.8 g, 57 mmol) in a manner similar to that described above
by heating for 2 h at 80 ꢃC. The crude product was purified by re-
crystallization from methanol, ethyl acetate, and n-hexane to afford
a brown crystal. Yield: 48% (0.55 g); mp 196e197 ꢃC (dec); 1H NMR
uid. Yield: 87% (0.64 g); 1H NMR (400 MHz, CDCl3)
d
1.51 (br s, 3H),
(400 MHz, CDCl3)
d
4.70 (s, 8H), 6.58 (s, 4H), 7.11e7.15 (m, 4H), 7.29
58.38,
2.93 (t, 2H), 3.17 (t, 2H), 6.63 (d, 2H), 6.70 (t, 1H), 7.17 (t, 2H). 2-
(Chloromethyl)pyridine hydrochloride (1.8 g, 11 mmol) was treated
with a 20% aqueous NaOH solution and extracted with dichloro-
methane and the organic phase was dried over anhydrous Na2SO4.
After Na2SO4 was filtered out and the solvent was evaporated off,
a solution of 2-(chloromethyl)pyridine in benzene (3 ml) was
added to a solution of N-phenylethylenediamine (0.69 g, 5.1 mmol),
which was prepared as described above, and triethylamine (5.1 g,
51 mmol) in benzene (4 ml) and stirred for 17 h at 80 ꢃC under an
argon atmosphere. After being cooled to room temperature and the
addition of diethyl ether, the inorganic by-products were removed
by washing with a saturated NaHCO3 solution and with brine. The
organic phase was dried over anhydrous Na2SO4. After the Na2SO4
was filtered out and the solvent was removed the crude product
was purified by column chromatography on silica gel (eluant: ethyl
acetate) to afford 2a as a red-brown viscous liquid. Yield: 69%
(d, 4H), 7.58 (t, 4H), 8.54 (d, 4H); 13C NMR (100 MHz, CDCl3)
d
114.73, 121.49, 122.25, 137.06, 141.23, 149.93, 159.95; HRMS (EI):
calcd for C30H28N6: 472.2375. Found: 472.2360.
4.2.6. 2,20-Dipicolylaminobenzene (3b). This compound was pre-
pared from 2-(chloromethyl)pyridine hydrochloride (9.5 g,
58 mmol), aniline (1.8 g, 19 mmol), and triethylamine (5.8 g,
57 mmol) in a similar manner to that described above by heating
for 2 h at 80 ꢃC. Yield: 55% (2.9 g) as a brown crystal; mp
111e112 ꢃC; 1H NMR (400 MHz, CDCl3)
d
4.83 (s, 4H), 6.67e6.75 (m,
3H), 7.11e7.21 (m, 4H), 7.27 (d, 4H), 7.61 (t, 4H), 8.59 (d, 2H); 13C
NMR (100 MHz, CDCl3) 57.73,112.94, 117.62,121.22,122.41,129.70,
d
137.20, 148.63, 150.13, 159.28; HRMS (EI): calcd for C18H17N3:
275.1422. Found: 275.1401. Anal. Calcd for C18H17N3: C 78.52, H
6.22, N 15.26. Found: C 78.44, H 6.19, N 15.37.
(1.1 g); 1H NMR (400 MHz, CDCl3)
4H), 6.58 (d, 2H), 6.65 (t, 1H), 7.07e7.18 (m, 4H), 7.41 (d, 2H), 7.60 (t,
d
2.86 (t, 2H), 3.17 (t, 2H), 3.88 (s,
4.2.7. p-(N,N-Dimethylamino)-2,20-dipicolylaminobenzene
(3c). This compound was prepared from 2-(chloromethyl)pyridine

T. Maruyama et al. / Tetrahedron 67 (2011) 6927e6933
6933
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d
2.80 (s, 6H), 4.75 (s, 4H), 6.69 (m, 4H), 7.14 (m, 2H), 7.31 (d,
42.31,
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58.47, 114.72, 115.83, 121.52, 122.26, 137.09, 141.25, 144.12, 149.93,
160.00; HRMS (EI): calcd for C20H22N4: 318.1844. Found: 318.1868.
4.2.8. 2,20-Dipicolylaminomethylbenzene (4). This compound was
prepared from 2-(chloromethyl)pyridine hydrochloride (3.7 g,
22 mmol), benzylamine (1.0 g, 9.3 mmol), and triethylamine (4.7 g,
47 mmol) in a similar manner to that described above by heating for
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CDCl3)
2H,), 7.31 (t, J¼7.4 Hz, 2H,), 7.42 (d, J¼7.0 Hz, 2H,), 7.59 (dt, 2H), 7.66
(t, 2H), 8.52 (d, 2H); 13C NMR (100 MHz, CDCl3)
58.94, 60.41,122.33,
d
3.69 (s, 2H), 3.81 (s, 4H), 7.10e7.17 (m, 2H), 7.23 (t, J¼7.4 Hz,
d
123.16, 127.45, 128.71, 129.25, 136.81, 139.39, 149.37, 160.23; HRMS
(EI): calcd for C19H19N3: 289.1579. Found: 289.1582.
€
€
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Acknowledgements
This work was supported by a Grant-in-Aid (19550137) and the
Global COE from the Ministry of Education, Culture, Sports, Science
and Technology of Japan.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.06.078.
References and notes
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