Substitution effect, absorption, and fluorescence behaviors of 11,12-benzo-1,7,10,13-tetraoxa-4-azacyclopentadec-11-ene (Benzoaza-15-crown-5) derivatives upon cation complexation in solvent extraction

Article abstract of DOI:10.1021/jo0107148

Substitution effect, absorption, and fluorescence behaviors of some benzoaza-15-crown-5 derivatives upon cation complexation in solvent extraction were studied. The introduction of a substituent on the nitrogen atom in benzoaza-15-crown-5 enhanced extractabilities in the solvent extraction of aqueous alkali metal picrates. The nondonating substituents raised the cation selectivity for Na⁺ over K⁺, but the donating substituents reduced the cation selectivity. The absorption and fluorescence spectral behavior was different with the alkali metal cations.

Full text of DOI:10.1021/jo0107148

J . Org. Chem. 2002, 67, 3533-3536
3533
Ch a r t 1
Su bstitu tion Effect, Absor p tion , a n d
F lu or escen ce Beh a vior s of
11,12-Ben zo-1,7,10,13-tetr a oxa -4-a za -
cyclop en ta d ec-11-en e
(Ben zoa za -15-cr ow n -5) Der iva tives u p on
Ca tion Com p lexa tion in Solven t Extr a ction
Mitsunobu Nakamura,*,† Hideaki Yokono,†
Ken-ichi Tomita,‡ Mikio Ouchi,‡ Masamichi Miki,† and
Reizo Dohno†,§
Department of Engineering Science and Department of
Applied Chemistry, Himeji Institute of Technology,
2167 Shosha, Himeji, Hyogo 671-2201, J apan
Sch em e 1
nakamura@esci.eng.himeji-tech.ac.jp
Received J uly 16, 2001
Abstr a ct: Substitution effect, absorption, and fluorescence
behaviors of some benzoaza-15-crown-5 derivatives upon
cation complexation in solvent extraction were studied. The
introduction of a substituent on the nitrogen atom in
benzoaza-15-crown-5 enhanced extractabilities in the solvent
extraction of aqueous alkali metal picrates. The nondonating
substituents raised the cation selectivity for Na+ over K+,
but the donating substituents reduced the cation selectivity.
The absorption and fluorescence spectral behavior was
different with the alkali metal cations.
Since it is known that azacrown ethers have an
advantage in synthetic feasibility over all oxygen ana-
logues, azacrown ethers with N-substituents have been
designed to enhance cation binding ability and also to
partly mimic the dynamic complexation exhibited by
natural macrocyclic ligands.1 Indeed, several groups have
shown that some azacrown ethers with N-substituents
perform generally well in cation binding and transport,
compared with the parent or reference azacrown ethers.2
However, less attention has been paid to the cation
binding properties for benzoazacrown ethers. In particu-
lar, the effects of an N-substituent on the cation binding
properties of, and the cation selectivity for, benzoaza-
crown ethers have not been studied systematically, to the
best of our knowledge. Since benzoazacrown ethers have
chromophores in their skeleton, the cation complexation
of benzoazacrown ethers can be observed via absorption
or luminescence. Recently, macrocyclic ethers have been
studied extensively as cation complexing agents that are
significant for chemistry and physiology.3
crown-5) derivatives, each with an N-substituent, were
studied: benzoaza-15-crown-5 1a , N-octylbenzoaza-15-
crown-5 1b, N-benzylbenzoaza-15-crown-5 1c, N-tetrahy-
drofurfurylbenzoaza-15-crown-5 1d , and N,N′-trimeth-
ylene-bis(benzoaza-15-crown-5) 1e. Here, we discuss the
cation binding abilities and cation selectivities of 1a -e
and the absorption and fluorescence behavior of 1e upon
cation complexation.
P r ep a r a tion of Ma ter ia ls. The benzoaza-15-crown-5
derivatives employed in this work are illustrated in Chart
1 and were prepared according to Scheme 1. The corre-
sponding chlorides were permitted to react with dietha-
nolamine to give N-octyldiethanolamine 2 and N-ben-
zyldiethanolamine 3. N-Tetrahydrofurfuryldiethanolamine
4 was prepared by reaction of diethanolamine with
tetrahydrofurfuryl tosylate 5 given from tetrahydrofur-
furyl alcohol and toluenesulfonyl chloride. 2,2′-(o-Phen-
(3) For example, see: (a) Hayashita, T.; Taniguchi, S.; Tanamura,
Y.; Uchida, T.; Nishizawa, S.; Teramae, N.; J in, Y. S.; Lee, J . C.;
Bartsch, R. A. J . Chem. Soc., Perkin Trans. 2 2000, 1003. (b) J i, H. F.;
Dabestani, R.; Brown, G. M.; Hettich, R. L. Photochem. Photobiol. 1999,
69, 513. (c) Kollmannsberger, M.; Rurack, K.; Resch-Genger, U.; Daub,
J . J . Phys. Chem. A 1998, 102, 10211. (d) Prodi, L.; Bolletta, F.;
Zaccheroni, N.; Watt, C. I. F.; Mooney, N. J . Chem. Eur. J . 1998, 4,
1090. (e) Cielen, E.; Tahri, A.; Heyen, K. V.; Hoornaert, G. J .; Schryver,
F. C.; Boens, N. J . Chem. Soc., Perkin Trans. 2 1998, 1573. (f) Alonso,
M. T.; Brunet, E.; Hernandez, C.; Rodriguez-Ubis, J . C. Tetrahedron
Lett. 1993, 34, 7465. (g) Sousa, L. R.; Son, B.; Trehearne, T. E.;
Stevenson, R. W.; Ganion, S. J .; Beeson, B. E.; Barnell, S.; Mabry, T.
E.; Yao, M.; Chakrabarty, C.; Bock, P. L.; Yoder, C. C.; Pope, S.
Synthesis and Study of Crown Ethers with Alkali-Metal-Enhanced
Fluorescence. In Fluorescent Chemosensors for Ion and Molecular
Recognition; Czarnik, A. W., Ed.; ACS Symposium Series 538; Ameri-
can Chemical Society: Washington, DC, 1992; pp 10-24.
In the present work, the following 11,12-benzo-1,7,10,-
13-tetraoxa-4-aza-cyclopentadec-11-ene (benzoaza-15-
† Department of Engineering Science.
‡ Department of Applied Chemistry.
§ Deceased.
(1) Gokel, G. W. Crown Ethers
& Cryptands: Monographs in
Supramolecular Chemistry No.3; Royal Society of Chemistry: Cam-
bridge, England, 1991; p 79.
(2) Ouchi, M.; Mishima, K.; Dohno, R.; Hakushi, T. Cation-Binding
Properties of Sodium-Selective 16-Crown-5 Derivatives. In Phase-
Transfer Catalysis; Halpern, M. E., Ed.; ASC Symposium Series 659;
American Chemical Society: Washington, DC, 1997; pp 293-300. Liu,
Y.; Han, B. H.; Inoue, Y.; Ouchi, M. J . Org. Chem. 1998, 63, 2144.
Schultz, R. A.; White, B. D.; Dishong, D. M.; Arnold, K. A.; Gokel, G.
W. J . Am. Chem. Soc. 1985, 107, 6659.
10.1021/jo0107148 CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/17/2002

3534 J . Org. Chem., Vol. 67, No. 10, 2002
Notes
Ta ble 1. Extr a ction of Meta l P icr a tesa a n d Cr ow n Eth er
organic (org) phase containing ligands (L) is expressed
by eq 1,5
Distr ibu tion Coefficien ts (Kd )
extractability (%)b
Kd
M+ + A- + nLorg a (MLnA)org
(1)
Li+
Na+
K+
Rb+
Cs+
aq
aq
1a
1b
1c
1d
1e
0.3
1.5
0.5
33.9
3.9
1.4
24.6
9.5
43.8
21.5
0.5
2.7
1.3
27.0
25.8
0.3
2.4
0.8
13.3
20.8
0.3
2.0
0.4
7.3
5.4
0.047
0.005
0.010
0.019
0.015
where n gives the ligand:cation ratio.
The overall extraction equilibrium constants (Kex) are
given by eq 2.
a
Aqueous phase: [MOH] ) 10 mM, [picric acid] ) 3 mM.
Organic phase: [ligand unit] ) 3 mM, dichloromethane. Temper-
Kex ) DM/[A-]aq[L]org
(2)
n
b
ature: 25 °C. Extractability was defined as the percent picrate
extracted into the organic phase.
The distribution coefficient of alkali metal ions (DM) and
the concentration of free ligands in the organic phase
([L]org) after the establishment of the equilibrium are
calculated by eqs 3 and 4, respectively,
ylenedioxy)diethanol 6 was synthesized in the reaction
of catechol with 2-chloroethanol under an alkaline me-
dium and tosylated to 2,2′-(o-phenylenedioxy)diethanol
ditosylate 7. The ditosylate 7 was allowed to react with
2 to give 1b in a 9% yield, with 3 to give 1c in a 32%
yield, and with 5 to give 1d in a 7% yield. Parent
benzoazacrown 1a was derived from 1c in a 71% yield.
Compound 1e was prepared in a 21% yield by reaction
of 1a with 1,3-propanediol ditosylate 8 derived from 1,3-
propanediol.
Solven t Extr a ction . When a CH2Cl2 solution of 1a
(3.0 mol/dm3) and an aqueous solution of alkali metal
cations were shaken together for 30 min at 25 °C, 1a
preferably extracted Na+, which was a size-matched
cation to the hole cavity of 1a , at 24.8%. As shown in
Table 1, the extractability of 1a for the alkali metal
DM ) [MLnA]org/[M+]aq
(3)
(4)
[L]org ) ([L]i - n[MLnA]org)/(1 + Kd)
where [L]i represents the initial concentration of ligands
dissolved in the organic phase, and Kd is the distribution
coefficient of ligands between the aqueous and organic
phases (Kd ) [L]aq/[L]org). Equation 2 can be modified to
eq 5.
log(DM/[A-]aq) ) nlog[L]org + log Kex
(5)
cations decreased in the following order: Na+ > K+
>
Rb+ ≈ Cs+ ≈ Li+. Compounds 1b and 1c also effectively
extracted Na+. Derivative 1d gave the highest extract-
abilities for Li+, Na+, K+, and Cs+ among the benzoaza-
crown derivatives. In the solvent extraction of 1e, the
extractability for size-mismatched larger K+ was higher
than that for size-matched Na+.
A plot of log(DM/[A-]aq) versus log[L]org gives a straight
line of slope n determined by complex stoichiometry. The
overall extraction Kex is calculated from the intercept.6
In the present work, the quantitative solvent extraction
experiments with aqueous sodium and potassium pic-
rates were performed in the range of 1.0-5.0 × 10-3 mol/
dm3 crown concentrations. Figure 1 shows plots of the
extraction data for 1a -e according to eq 2. The extrac-
tions of Na+ and K+ gave straight lines of unit slopes,
and this clarified the formation of a stoichiometric 1:1
complex with Na+ and K+ for 1a -e.
Table 2 summarizes the calculated log Kex values as
well as relative cation selectivities for Na+ over K+
calculated from Kex. An N-substitution for a hydrogen
atom on the nitrogen atom in 1a raised the log Kex value
for the size-matched cation Na+; the log Kex values of
1b-e for Na+ were considerably larger than that of 1a .
Compounds 1d and 1e, in which the N-substituents
performed donating ligation, enhanced the log Kex values
for the size-mismatched larger cation K+ as well as Na+.
On the other hand, the introduction of a nondonating
substituent on the nitrogen atom in 1a slightly increased
the log Kex values of 1b and 1c for K+ compared with
that of 1a .
It should be noted that the introduction of a nondo-
nating n-octyl group in 1b remarkably raised the extract-
ability for size-matched Na+, while the extractabilities
for size-mismatched cations increased only slightly.
Similar results appeared for the benzyl group in 1c. In
contrast, 1d and 1e, possessing donating sites in the
tetrahydrofurfuryl and N-trimethylene-benzoaza-15-
crown-5 moieties, respectively, yielded higher extract-
abilities for the alkali metal cations employed in the
present work. These results indicate that nondonating
N-substituents such as n-octyl and benzyl groups are
more favorable for Na+ binding and that the oxygen atom
of the tetrahydrofurfuryl group in 1d is an effective donor
site for alkali metal cations. The higher extractabilities
for size-mismatched larger cations in 1e were attribut-
able to the biscrown effect reported previously.4
Table 1 also exhibits the distribution coefficients (Kd)
of 1 between the aqueous and organic phases (cf. Experi-
mental Section). The introduction of an N-substituent
remarkably suppressed the partition of the benzoaza-
crown ethers to the aqueous phase compared with the
parent benzoazacrown ether 1.
(5) The formation of benzoazacrown ether-cation complexes in an
aqueous phase was neglected throughout this work because the
distribution of these benzoazacrown ethers into water is minimal. For
example, the complex association constants (Ka) of 15-crown-5 in water
have been shown to be around 5, which is 3-4 orders of magnitude
lower than those in organic solvents. See: de J ong, F.; Reingoubt, D.
N. Stability and Reactivity of Crown Ether Complexes; Academic
Press: London, 1981; p 25 and the reference cited therein.
(6) Tsukube, H.; Furuta, H.; Odani, A.; Takeda, Y.; Kudo, Y.; Inoue,
Y.; Liu, Y.; Sakamoto, H.; Kimura, K. Determination of Stability
Constants. In Comprehensive Supramolecular Chemistry; Davies, J .
E. D., Ripmeester, J . A., Eds.; Pergamon Press: Elmsford, NY, 1996;
Vol. 8, p 425.
The overall extraction equilibrium between an aqueous
(aq) phase containing alkali metal picrates (MA) and an
(4) J eong, K. S.; Pyun, S. Y. Tetrahedron Lett. 1994, 35, 7041. He,
G. X.; Kikukawa, K.; Nishiyama, N.; Ohe, H.; Matsuda, T. Bull. Chem.
Soc. J pn. 1988, 61, 3785. Kikukawa, K.; He, G. X.; Abe, A.; Goto, T.;
Arata, R.; Ikeda, T.; Wada, F.; Matsuda, T. J . Chem. Soc., Perkin Trans.
2 1987, 135. Kimura, K.; Sakamoto, H.; Koseki, Y.; Shono, T. Chem.
Lett. 1985, 1241.

Notes
J . Org. Chem., Vol. 67, No. 10, 2002 3535
been proposed by many groups, with a size-mismatched
larger cation.7
We previously investigated the log Kex values and
cation selectivities of some aza-15-crown-5 ethers, each
having an N-substituent.8 Although the log Kex () 4.28)
value of N-octylaza-15-crown-5 ether for Na+ was nearly
equal to that of 1b, the log Kex () 3.72) value of
N-octylaza-15-crown-5 for K+ was higher than that of 1b.
This means that the benzoaza-15-crown-5 skeleton is
unfavorable for complexation with the larger cation K+
compared with the aza-15-crown-5 skeleton. The intro-
duction of a benzene ring to the aza-15-crown-5 skeleton
can reduce the flexibility of aza-15-crown-5 for complex-
ation with K+; the enthalpic loss upon complexation with
K+ for benzoaza-15-crown-5 is larger than that for aza-
15-crown-5.9 As a consequence, benzoaza-15-crown-5
exhibits a higher cation selectivity for Na+ than does aza-
15-crown-5.
Absor p tion a n d F lu or escen ce Sp ectr a of 1e. The
absorption spectrum of 1e changed with the addition of
alkali metal cations. Figure 2 shows the absorption
spectral changes of 1e in acetonitrile in the presence of
alkali metal cations. The absorption maximum of 1e
appeared at 275 nm and shifted slightly to a shorter
wavelength with the addition of sodium and potassium
perchlorates (Figures 2A and B, respectively). The optical
density at 275 nm decreased as the concentrations of Na+
and K+ increased. Similar decreases in absorbance ap-
peared in the cases of Rb+ and Cs+. In contrast, no
absorption spectral changes were observed in the pres-
ence of Li+ (Figure 2C); thus, 1e is capable of distin-
guishing Li+ from other alkali metal cations via absorp-
tion.
The absorption behavior reflects the manner of com-
plexation. Since the metal cation withdraws the non-
bonding electrons of the two oxygen atoms connected to
the benzene ring upon complexation, this process reduces
the electron-donating character of the oxygen to the
benzene ring. As a consequence, the absorption maximum
shifts to a shorter wavelength. The absence of a spectral
change in absorption for Li+ indicates that the complex-
ing power with Li+ is much smaller than that with other
cations.
Bisbenzoazacrown 1e fluoresced in acetonitrile and
reached its fluorescence maximum at 310 nm with
excitation of 260 nm light. The fluorescence spectrum of
1e also changed with the addition of the alkali metal
cations, and distinct values could be found by the effects
of Na+, K+, and Li+.10 As shown in Figure 3A, the
fluorescence intensity slightly increased as the concen-
tration of Na+ increased. The addition of potassium
perchlorate decreased the fluorescence intensity (Figure
3B). No spectral changes were observed in the presence
of Li+ (Figure 3C). The fluorescence of 1e illustrated the
F igu r e 1. Plots of log(DM/[A]aq) versus log[1]org obtained in
solvent extraction for (A) 1a , (B) 1b, (C) 1c, (D) 1d , and (E)
1e. Closed circle: Na+. Closed square: K+.
Ta ble 2. Extr a ction Equ ilibr iu m Con sta n ts (Kex) a n d
Ca tion Selectivitiesa
log Kex
selectivityb
Na+/K+
Na+
K+
1a
1b
1c
1d
1e
2.77
4.19
3.61
4.73
4.72
2.26
2.96
2.66
4.26
4.96
3.2
17
8.9
3.0
0.6
a
b
In a dichloromethane-water system at 25 °C. Calculated
from extraction equilibrium constants (Kex).
The introduced N-substituent dramatically affected the
relative cation selectivity for Na+ over K+. A specific
enhancement of the cation selectivity appeared with 1b
having an n-octyl group. The log Kex value of 1b for the
size-mismatched cation K+ slightly increased, contrary
to the large enhancement of the log Kex value for Na+,
thus yielding a higher relative selectivity for Na+ com-
pared with the parent 1a . Compounds 1d and 1e en-
hanced the log Kex values for K+ as well as those for Na+,
and thus the relative selectivities were almost unchanged
or lower than that of 1a .
Since bisbenzoazacrown ether 1e forms a stoichiomet-
ric 1:1 complex with K+, as suggested by the plot in
Figure 1, and substantially extracts size-mismatched
larger cations in the solvent extraction, it follows that
1e probably forms a sandwich-type complex, which has
(7) For example, see: Inoue, Y.; Nakagawa, K.; Hakushi, T. J . Chem.
Soc., Dalton Trans. 1993, 2279. Markovskii, L. N.; Rudkevich, D. M.;
Kal’chenko, V. I. J . Gen. Chem. USSR (Engl. Transl.) 1992, 62, 306.
Koudelka, P. H. J .; Belohradsky, M.; Stibor, I.; Zavada, J . Collect.
Czech. Chem. Commun. 1991, 56, 6, 1482. Tanaka, T.; Mizufune, H.;
Shono, T. Chem. Lett. 1990, 1419. He, G. X.; Kikukawa, K.; Ikeda, T.;
Wada, F.; Matsuda, T. J . Chem. Soc., Perkin Trans. 2 1988, 719.
(8) Unpublished data.
(9) Nakagawa, K.; Inoue, Y.; Hakushi, T. J . Chem. Res. Miniprint
1990, 2625. Takeda, Y. Bull. Chem. Soc. J pn. 1983, 56, 931. Takeda,
Y. Bull. Chem. Soc. J pn. 1982, 55, 2040.
(10) The fluorescence spectra were observed at a 260 nm excitation
wavelength at which the absorption optical density of 1e barely
changed with the addition of metal perchlorates.

3536 J . Org. Chem., Vol. 67, No. 10, 2002
Notes
F igu r e 2. Absorption spectral change of 1e (1 × 10-4 mol/dm3 in acetonitrile) in the presence of alkali metal cations (0-5 × 10-4
mol/dm3): (A) Na+, (B) K+, and (C) Li+.
F igu r e 3. Fluorescence spectral change of 1e (1 × 10-4 mol/dm3 in acetonitrile) in the presence of alkali metal cations: (A) Na+
(0-5 × 10-4 mol/dm3), (B) K+ (0-1 × 10-3 mol/dm3), and (C) Li+ (0-5 × 10-4 mol/dm3).
complexing difference between Na+ and K+, which cannot
be distinguished via absorption.
quenchable conformation in a sandwich-type complex
with K+.
Although the fluorescence intensity of 1e decreased
with increasing concentration of K+, Sousa et al. reported
that the fluorescence intensity of dimethylene-bis(naph-
thoazacrown) increased with increasing concentration of
metal cations.3g They stated that the nonbonding elec-
trons on nitrogen atoms intramolecularly quench the
fluorescence under the free condition and that the com-
plexation with metal cations decreases this intramolecu-
lar quenching because the nonbonding electrons of the
nitrogen atom are consumed in coordination. In our
system, the fluorescence enhancement in 1e-Na+ is due
to a similar mechanism. On the contrary, the decrease
in fluorescence intensity in 1e-K+ cannot be explained
by this mechanism. Further investigation of the fluores-
cence behavior of 1e is needed. The following is a
plausible explanation at present. As 1e forms a sandwich-
type complex, in which the two benzene rings are close
to each other, with K+, intramolecular quenching by the
nonfluorescing benzene ring probably occurs and sur-
passes the fluorescence enhancement due to complexation
with K+. Since the linker length and the crown-ring size
of dimethylene-bis(naphthoazacrown) are different from
those of 1e, two naphthyl rings probably form an un-
The introduction of a substituent on the nitrogen atom
in 1a enhanced extractabilities in the solvent extraction
of aqueous alkali metal picrates. The nondonating sub-
stituents in 1b and 1c raised the cation selectivity for
Na+ over K+ relative to that of 1a , but the donating
substituents in 1d and 1e reduced the cation selectivity
relative to that of 1a . The nondonating substituents in
1b and 1c induced more a favorable conformation for
size-matched Na+, and the oxygen atoms of the substit-
uents in 1d and 1e are effective donor sites for not only
Na+ but also other alkali metal cations. The absorption
and fluorescence spectral behavior of 1e was different
with the alkali metal cations. Bisbenzoazacrown 1e was
capable of discriminating between Li+, Na+, and K+ via
absorption and fluorescence.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for solvent extraction, determination of ligand distri-
bution coefficients, and the preparations of compounds 1-8.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O0107148