Synthesis of tripodands with multiple hydroxyl and amide groups exhibiting fluorescent anion sensing

Article abstract of DOI:10.1080/10610278.2010.531139

Novel tripodal receptors (T2 and T3) having multiple hydroxyl and amide groups with long alkyl chains (N-dodecylamino and N,N-didodecylamino groups, respectively) were prepared. The broadening of proton signals observed in the ¹H NMR spectrum o

Full text of DOI:10.1080/10610278.2010.531139

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Synthesis of tripodands with multiple hydroxyl and
amide groups exhibiting fluorescent anion sensing
Jie Hao a , Kazuhisa Hiratani a , Naohiro Kameta b & Toru Oba a
a Department of Applied Chemistry , Utsunomiya University , 7-1-2 Youtou, Utsunomiya,
321-8585, Japan
b National Institute of Advanced Industrial Science and Technology , Tsukuba Central 5, 1-1-1
Higashi, Tsukuba, 305-8565, Japan
Published online: 13 Apr 2011.
To cite this article: Jie Hao , Kazuhisa Hiratani , Naohiro Kameta & Toru Oba (2011) Synthesis of tripodands with multiple
hydroxyl and amide groups exhibiting fluorescent anion sensing, Supramolecular Chemistry, 23:03-04, 319-328, DOI:
10.1080/10610278.2010.531139
To link to this article: http://dx.doi.org/10.1080/10610278.2010.531139
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Supramolecular Chemistry
Vol. 23, Nos. 3–4, March–April 2011, 319–328
Synthesis of tripodands with multiple hydroxyl and amide groups exhibiting
fluorescent anion sensing
Jie Haoa, Kazuhisa Hiratania*, Naohiro Kametab and Toru Obaa
aDepartment of Applied Chemistry, Utsunomiya University, 7-1-2 Youtou, Utsunomiya 321-8585, Japan; bNational Institute of Advanced
Industrial Science and Technology, Tsukuba Central 5, 1-1-1 Higashi, Tsukuba 305-8565, Japan
(Received 10 August 2010; final version received 7 October 2010)
Novel tripodal receptors (T2 and T3) having multiple hydroxyl and amide groups with long alkyl chains (N-dodecylamino
1
and N,N-didodecylamino groups, respectively) were prepared. The broadening of proton signals observed in the H NMR
spectrum of compounds T2 and T3 in a non-polar solvent (CDCl3) was attributed to intermolecular and/or intramolecular
hydrogen bonding. In the fluorescence spectrum, the addition of Bu4NF to the solution of receptors T2 and T3 caused the
drastic increase in fluorescence intensity compared with the addition of other anion species.
Keywords: tripodand; tandem Claisen rearrangement; anion recognition; hydrogen bonding
1. Introduction
besides with long alkyl end groups. Isobutenyl ether part is
introduced into each arm because of the generation of
plural hydroxyl groups via TCR. The introduction of long
alkyl end group to tripodal compounds aims not only to
improve the solubility towards organic solvents but also to
assemble each arm intramolecularly (23). In T2 and T3,
we directly connected monododecyl and didodecyl groups
to N-atom of each terminal amide group, respectively. For
comparison of NMR spectroscopic behaviours, we used
T1, which has been previously reported (22), in this study.
In addition, tripodands, T4 and T5, and linear compound
L1 were also prepared in order to compare the behaviours
in the solution. Their binding ability with anions was
investigated by 1H NMR and fluorescence spectra in non-
polar and polar solvents.
Various anions play important roles in chemical processes
and biochemical systems, where the majority of enzyme
substrates and co-factors are also anionic (1–4). Therefore,
the development of responsive and selective artificial anion
receptors is of great interest and significance (5, 6). So far,
compounds containing multi-hydrogen bonding sites have
gained considerable attention due to their ability of
complexation towards ionic and/or neutral molecules.
Several strategies for achieving tetrahedral anion recog-
nition have been employed (7, 8). Tripodal receptors,
which are regarded to be between cyclic and dipodal
ligands with regard to preorganisation, are believed to be
able to make a complex with guest molecules more
effectively than analogous dipodal ones (9–11). We have
focused on the study of artificial receptors having multi-
hydroxyl groups generated via tandem Claisen rearrange-
ment (TCR) (12) and amide NZH groups in order to
improve the recognition ability towards anions (13–20).
Recently, we have reported the synthesis of tripodal
compound having plural hydroxyl groups by TCR, which
has been proved to be an excellent way to generate plural
hydroxyl groups from the precursors having isobutenyl
ether (21). More recently, the tripodal receptor (T1)
shown in Figure 1 has been reported to exhibit the binding
ability towards acetate, dihydrogen phosphate and fluoride
ions with relatively strong affinity but less selectivity
among them to form 1:1 complex with them in chloroform
solution (22).
2. Results and discussion
2.1 Synthesis of tripodands
The synthetic procedures of tripodands T2–T5 are
illustrated in Scheme 1. Compound 1 was obtained in
60% yield by the reaction of 2-hydroxy-3-naphthoic acid
methyl ester with NaH followed by the addition of three
equimolar excess of 3-chloro-2-methyl-1-propene. Com-
pound 2 was obtained by hydrolysis over two steps from
compound 1. Compound 4 was obtained by the reaction of
1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene (24, 25) in
dry THF with acid chloride 3, which was prepared by the
reaction of 2 with thionyl chloride. Compound 5 was
obtained by the reaction with 2-hydroxy-3-naphthoic
acid methyl ester with NaH followed by the addition of
In this work, we newly designed and prepared two
tripodal compounds T2 and T3 with three long arms
*Corresponding author. Email: hiratani@cc.utsunomiya-u.ac.jp
ISSN 1061-0278 print/ISSN 1029-0478 online
q 2011 Taylor & Francis
DOI: 10.1080/10610278.2010.531139
http://www.informaworld.com

320
J. Hao et al.
The chemical shifts of OHa, OHb and naphthyl-Hc in
CDCl3, which are located at the inner hydroxyl OHa, outer
hydroxyl OHb and the four position of outer naphthyl group
of T2 and T3, respectively, are shown in Figure 3(A) and
(B). It should be noticed that the proton signals of OHa and
OHb in CDCl3 for phenolic-OH protons of T2 appear
around 12 ppm. On the other hand, in T3 the signal at
11.8 ppm is assigned to OHa, whereas the chemical shift
of OHb which hardly forms intramolecular six-membered
hydrogen bond structure appears around 9.5 ppm.
The upfield shift of OHb proton signal of T3 means the
decrease in the hydrogen donating ability of OH group
implying the comparable decline in the acidity of OH
proton (26). These behaviours of the two protons of OHa
and OHb in both cases may be concerned with anion
recognition properties of T2 and T3 discussed later.
Figure 1. Tripodand T1 with three hydroxyl and three amide
groups.
compound 4. Compound 5 was converted into compound 6
by hydrolysis. Compounds 7a, 7b and 7c were obtained by
the dehydration reaction of 6 with N-dodecylamine, N,N-
didodecylamine and N-butylamine, respectively, using 2-
chloro-1-methylpyridinium iodide (CMPI). Finally, com-
pounds T2–T4 was obtained by TCR. On the other hand,
T5 was obtained by TCR of ester 5.
From the above-mentioned results, it is suggested that
the OH proton signals of T2 and T3 could be varied by the
concentration of ligands in CDCl3, because all of
the protons signals become broadened in CDCl3 implying
the formation of H-bonding as shown in Figure 2, and the
chemical shifts of OH protons largely depend upon the
substituent on N-atom of the terminal group as shown in
Figure 3. In order to elucidate such kind of behaviours, we
carried out 1H NMR dilution experiment of T2 and T3 in
CDCl3. The 1H NMR chemical shift variation of OHa and
OHb in T2 and T3 was observed as shown in Figure 4. It is
easy to distinguish the signal OHa at about 12 ppm and the
signal OHb at about 9 ppm in T3 (Figure 4(B)). The signal
at about 12 ppm is assigned to OHa because OH proton of
T1 appears at the same region as OHa of T3. The structure
of T1 is the same as the central part of T2 and T3. With
decreasing concentration of T3, the OHa signal gradually
moves upfield and the OHb signal showed relatively little
shift over a concentration range from 1.0 £ 1022 to
6.25 £ 1024 M. It is presumed that amide groups
neighbouring OHa in T3 form six-membered hydrogen
bonding structure between amide carbonyl and hydroxyl
(OHa) groups intramolecularly, because it might be
sterically unfavourable for inner OHa to form it
intermolecularly. On the other hand, one of the OH signals
gradually moves upfield and another one gradually moves
downfield upon decreasing concentration of T2. Thus, it is
assigned that the OH signal moving upfield is OHa and the
OH signal moving downfield is OHb, because the same
behaviour of phenolic OHa of T3 as that of T2 was
observed as shown in Figure 4(B). These results indicate
that the mono N-alkyl group on each arm does not seem to
disturb the formation of hydrogen bonding between amide
carbonyl and OHb proton of T2, because the chemical shift
of OHb appears in the same range as that of OHa. On the
contrary, N,N-disubstituted alkyl groups of T3 disturb to
make a six-membered hydrogen bonding structure between
OHb and amide groups because of the bulkiness of
disubstituted alkyl groups.
The synthetic procedure of L1 is illustrated in Scheme 2.
Compound L1 was prepared starting from 3 according
to a similar route as shown in Scheme 1. Compound L1
has partly the same structure as T2. These compounds
1
were characterised by H NMR, FT-IR, mass spectra and
elemental analysis.
2.2 1H NMR spectroscopic behaviours of tripodands
1H NMR study of T1–T3 was performed using CDCl3 and
DMSO-d6 as solvents. The results are shown in Figure 2.
In CDCl3, compounds T2 and T3 gave broadening signals
1
in the H NMR spectrum at room temperature (258C),
although compound T1 shows sharp signals under the
same conditions. It is suggested that intermolecular or
intramolecular hydrogen bonding is formed in the case of
T2 and T3 because they have six phenolic OH and six
amide groups in a molecule. Therefore, DMSO-d6 was
used in the measurement of 1H NMR spectrum of T2 and
T3 in order to break hydrogen bonding. Interestingly,
compound T2 was easily soluble in DMSO-d6, whereas
T3 having totally six dodecyl terminal groups was
insoluble in DMSO-d6 at all. It means that T3 is too
hydrophobic to be soluble in a polar solvent, i.e. DMSO.
When the 1H NMR spectrum of T2 was measured in
DMSO-d6, the signals of T2 drastically became sharp
compared with those in CDCl3, implying that hydrogen
bonding was broken by the presence of DMSO-d6, which
has the ability of H-bonding cleavage. A similar behaviour
was also observed in the 1H NMR spectrum of T2 and T3
in the mixed solvent (CDCl3: DMSO-d6 (9:1)). That is, the
signals of T2 and T3 in the mixed solvent became sharper
than those in CDCl3. It is suggested that the presence of
DMSO brings the cleavage of either intramolecular or
intermolecular H-bonding.

Supramolecular Chemistry
321

322
J. Hao et al.
Me
Me
NH
NH2C12H25
NH
O
O
Cl
Cl
NH2
O
O
O
O
O
TCR
Me
HO
HO
Et3N, THF
O
O
O
R
R
R = NHC12H25
L1 R = NHC12H25
Scheme 2. Synthetic route of L1.
The interaction through the hydrogen bonding
1
observed in the H NMR dilution experiment of T2 and
bonding intermolecularly in this concentration range,
(2) T1 with three short arms also has no intermolecular
interaction and (3) T5 with three methyl ester parts instead
of N-alkyl end group also has no interaction among three
arms intramolecularly and intermolecularly. In addition to
these results there is no interaction among three arms,
whereas the intramolecular six-membered hydrogen
bonding between amide carbonyl and hydroxyl groups is
surely formed in CDCl3 because OH protons neighbouring
the CONH group shift downfield abnormally in every case.
On the other hand, the 1H NMR chemical shift variation of
T4 with short N-substituted group (n-butyl) is similar to
the behaviour of T2 under the same conditions as shown in
Figure 5. With decreasing concentration of T4, one
broadening OH proton signal on each arm gradually shifts
upfield and mostly disappears at a lower concentration
T3 should be concerned with the behaviours of the guest
recognition. Compounds L1, T4 and T5 (see Schemes 1
and 2) were newly synthesised for comparison with T2
1
concerning the behaviours in the solution. The H NMR
dilution experiment in CDCl3 using tripodands T1, T4 and
T5 and a linear compound L1 as a model of one arm of T2
was carried out to study the behaviours of hydrogen
bonding in the concentration range from 1.0 £ 1022 to
1.25 £ 1023 M. No change in the chemical shifts was
observed at all in the dilution experiment of L1, T1 and
T5. These results suggest that three terminal parts of
tripodands play an important role to the cooperative
formation of intramolecular hydrogen bonding from the
following facts: (1) L1 has no interaction of hydrogen
Figure 2. 1H NMR spectrum of T1–T3 in CDCl3 and T2, T3 in CDCl3:DMSO-d6 (9:1); T2 in DMSO-d6.

Supramolecular Chemistry
323
Figure 5. 1H NMR dilution experiments of T5 in CDCl3:
(a) conc. ¼ 1.0 £ 1022, (b) 5.0 £ 1023, (c) 2.5 £ 1023, and
(d) 1.25 £ 1023 M.
Figure 3. Intramolecular hydrogen bonding pathway proposed
for the part of (A) T2 and (B) T3 (in CDCl3, conc. ¼ 0.01 M).
(Figure 5(d)), whereas the signal of the other OH proton
overlaps with the former one, and then rapidly disappears
in the lower concentration range. These results imply that
the intramolecular hydrogen bond among three arms of T2
and T4 may form in the higher concentration range in
addition to the six-membered H-bonding structure in each
arm in a non-polar solvent.
colour) in T3 hardly shifts as shown in Figure 4(B). This
presumption might also be supported by the steric
hindrance due to N,N-didodecyl end groups neighbouring
OHb. In our previous work (22), we found that hydroxyl
and amide protons in T1 strongly interact with F2, H2PO42
and AcO2 in CDCl3 to bring the drastic change in their
chemical shifts in the 1H NMR spectrum. This fact implies
that the anion binding sites of T3 might be OHa and amide
groups close to the central benzene ring. Thus, the anion
binding ability strongly depends upon the N-substituted
group. The N,N-didodecylamino group in T3 surely
disturbs the binding towards anion guests in CDCl3. In
addition, there is little change in the 1H NMR spectrum in
both cases of T2 and T3 when other anions such as Cl2,
Br2, I2 and HSO42 were added into the solution of CDCl3.
In the 1H NMR titration experiment of T2 with F2, two
OH signals showed downfield shifts due to hydrogen bond
with F2 as shown in Figure 7. In the concentration
(1.25 £ 1023 M) of T2, we can discriminate that the proton
peak at lower magnetic field is due to outer OHb and the
other one at higher magnetic field is due to inner OHa
(see Figure 4(A)-d). However, it should be noticed that the
signal of OHa proton in T2 moves downfield faster than
that of OHb when increasing the ratio of guest anion. This
result suggests that inner OHa exhibits stronger ability for
complexation with F2 than outer OHb in T2.
2.3 Complexation of T2 and T3 with anions
Both tripodands T2 and T3 have totally six hydroxyl and
six amide groups in their three arms. Therefore, these
compounds might be expected to exhibit the anion binding
ability as host molecules. 1H NMR spectrum of T2 and T3
was measured in CDCl3 in the presence of anions such as
F2, AcO2 and H2PO24 (Figure 6). In the absence of anions,
the singlet chemical shifts assigned to Hc of the naphthyl
protons (see Figure 3) were observed at 7.77 and 7.64 ppm
in T2 and T3, respectively. Upon complexation of F2,
AcO2 and H2PO24 , it should be noted that the singlet peak
Hc of T2 shifts downfield, whereas the singlet peak Hc of
T3 does not shift at all even after addition of fluoride ion as
shown in Figure 6(B). It is inferred that there is no
interaction between outer OHb of host T3 and any guest
anion because the naphthyl proton Hc (marked in red
Fluorescent spectrum of receptors T1, T2 and T3 was
also measured in the absence and presence of various
anions such as F2, Cl2, Br2, I2, HSO42, AcO2 and H2PO24
having tetra-n-butyl ammonium ion as a counter cation.
As shown in Figure 8, when each anion was added into
the CHCl3 solution containing each receptor, compound
T1 exhibits prominent response towards anions ordered
as follows: fluoride . acetate . dihydrogen phosphate
ions. On the other hand, compounds T2 and T3 showed
selective and significant increase in fluorescence intensity
only towards F2 ion in a polar or non-polar solvent. In
polar solvents such as DMSO or DMSO:H2O ¼ 24:1, the
ratio of the fluorescence intensity (fluoride ion vs. other
(A)
a
(B)
a
OHa OHb
OHa
OHb
b
c
b
c
d
e
d
e
12
10
12
10
Figure 4. 1H NMR dilution experiments of (A) T2 and (B) T3
in CDCl3: (a) conc. ¼ 1.0 £ 1022, (b) 5.0 £ 1023, (c) 2.5 £ 1023
,
(d) 1.25 £ 1023, (e) 6.25 £ 1024 M.

324
J. Hao et al.
(A)
(B)
CDCl3
NHNH
CDCl3
NH
Hc
T3
Hc
T2
Hc
T3+F–
NH
T2+F–
NH NH
Hc
Hc
T3+AcO–
NH
T2+AcO–
NH NH
Hc
Hc
T3+H2PO4–
NH
T2+H2PO4–
Hc
NH
NH
9
8
7
9
8
7
1
Figure 6. H NMR spectra of (A) T2 and T2 added with F2, H2PO42 and AcO2 and (B) T3 and T3 added with F2, H2PO24 and AcO2.
All of the spectra are measured in CDCl3.
ions) in the case of T2 does not change so much compared
with the result in CHCl3, although the measured values
change depending upon the conditions. On the basis of
previously reported anion sensing phenomenon, the
appearance of these new peaks would be just due to the
formation of intermolecular excited state proton transfer
(27) in anion complexes by weakening the intramolecular
hydrogen bonding between OH and carbonyl groups. It
should be noted that T2 can be used as a fluorescent
sensing agent for fluoride ion with high selectivity not only
in a non-polar solvent but also in a polar solvent containing
water different from T3 which is insoluble in a polar
solvent, i.e. DMSO, because it is a practically important
factor that the ionic guest can be recognised selectively in a
polar solvent, in particular, in an aqueous solvent.
3. Conclusion
Novel tripodal receptors T2 and T3 having multiple
hydroxyl and amide groups either with N-dodecylamino
end group or with N,N-didodecylamino end group,
respectively, were successfully synthesised via TCR in
order to investigate the behaviours of the interaction
among three arms and the ability for complexation with
1
anions. When the H NMR spectrum of T2 and T3 was
measured either in polar or non-polar solvent, the chemical
shifts of outer OHb proton changed depending upon the
substituent on terminal amide group. In T2 having
N-monosubstituted alkyl group, the outer OHb in each
arm can form strong hydrogen bonding intramolecularly,
whereas in T3 having totally six N,N-disubstituted alkyl
groups, OHb has little hydrogen bonding interaction not
only intermolecularly but also intramolecularly because of
the steric hindrance. In the investigation of their anion
binding behaviours, we showed that T2 and T3 with longer
three arms compared with T1 exhibited much higher
fluorescent sensitivity towards that fluoride ion. Tripodand
T2 having two kinds of primary amide groups in one arm
in a molecule can recognise anions even in a polar solvent
such as DMSO and aqueous DMSO. Tripodand T3 can
exhibit fluorescent fluoride sensing in CHCl3, but not in
DMSO because of insolubility. In the fluorescence
spectrum, T2 exhibits highly selective emission around
500 nm towards fluoride ion among F2, Cl2, Br2, I2,
HSO24 , AcO2 and H2PO24 ions.
T2 + F
OHb
OHa
0.0
0.2
0.5
1.0
1.5
4.0
14
12
10
8
6
Figure 7. 1H NMR spectral change with the addition of F2
to T2 in CDCl3 (conc. ¼ 1.25 £ 1023 M).

Supramolecular Chemistry
325
Figure 8. Emission spectral changes of (A) T1 (1.0 £ 1025 M) upon addition of various anions in CHCl3, (B) T2 (1.0 £ 1025 M) upon
addition of various anions in CHCl3, (C) T3 (1.0 £ 1025 M) upon addition of various anions in CHCl3, (D) T3 (1.0 £ 1025 M) upon
addition of various anions in DMSO and (E) T3 (1.0 £ 1025 M upon addition of various anions in DMSO:H2O ¼ 24:1).
4. Experimental
the residue was dissolved in diethyl ether (100 ml) and
the organic layer was washed three times with water,
dried over MgSO4 and evaporated under vacuum.
The crude product was chromatographed on silica gel
with AcOEt:hexane (1:20) as an eluent to give compound 1
(15.3 g, 0.053 mol, 55%) as a white solid. 1H NMR
(500 MHz, CDCl3): d 3.96 (s, 3H), 4.31 (s, 2H), 4.81 (s,
2H), 5.45 (s, 1H), 5.53 (s, 1H), 7.24 (s, 1H), 7.41 (m, 1H),
7.54 (m, 1H), 7.74 (d, J ¼ 8.0 Hz, 1H), 7.84 (d, J ¼ 8.0 Hz,
1H), 8.36 (s, 1H).
4.1 General information
All reagents were obtained from commercial suppliers and
used without further purification unless otherwise stated.
1H NMR spectrum was determined on a Varian NMR
1
System 500. Chemical shifts from TMS in CDCl3 for H
NMR are reported in parts per million (ppm), calibrated to
the residual solvent peak set, with coupling constants
reported in J-value (Hz). Column chromatography was
˚
carried out using Merck silica gel 60 A (230–400 mesh).
Recycling preparative GPC–HPLC was carried out on JAI
LC-908. Mass spectrum was recorded using a Bruker
Daltonics Autoflex MALDI-TOF Mass Spectrometer with
Scout-MTP Ion Source. IR spectrum was recorded with a
Jasco FTIR-430 spectrophotometer with samples as KBr
pellets in the 4000–400 cm21 range. Elemental analyses
were performed on Fisons EA-1108 instrument.
4.3 3-(3-Hydroxycarbonyl-2-naphthoxy)-2-
hydroxymethyl-1-propene (2)
Compound 1 (6.00 g, 0.02 mol) was dissolved in 50 ml of
dry DMF and then potassium acetate (3.04 g, 0.04 mol)
was added to the solution. The reaction mixture was stirred
for 12 h at 608C and the solvent was removed by a vacuum
pump. To the residue was added water (200 ml), and the
insoluble solid was separated by filtration, and washed
with water (250 ml) to remove excess DMF. The solid was
dried in vacuo. The solid obtained was used without
further purification.
4.2 3-(3-Methoxycarbonyl-2-naphthyloxy)-2-
chloromethyl-1-propene (1)
To a solution of 2-hydroxy-3-naphthoic acid methyl ester
(20.2 g, 0.1 mol) in dry DMF (200 ml) was added 1.2eq
NaH (2.88 g, 0.12 mol), and the mixture was stirred for 1 h
at room temperature. Each 10 ml of the mixture was added
to the dry DMF (50 ml) solution of 3-chloro-2-chloro-
methyl-1-propene (37.5 g, 0.3 mol) every 30 min while
stirring at 608C under Ar. The solution was stirred at 608C
overnight after addition of the mixture. After removal
of DMF under reduced pressure by a vacuum pump,
The solid was dissolved in EtOH and THF (200 and
20 ml, respectively) solvents and NaOH (8.00 g, 0.20 mol)
was added. After stirring for 12 h at 608C, the solvents
(EtOH and THF) were removed under reduced pressure
and to the aqueous solution was added conc. HCl dropwise
until the pH paper indicated acidic. The white precipitate
was filtered and washed with water, yielding white solid 2

326
J. Hao et al.
(4.80 g, 0.018 mol, 90%, for the two steps). 1H NMR
(500 MHz, CDCl3): d 4.36 (s, 2H), 4.93 (s, 2H), 5.40 (s,
1H), 5.43 (s, 1H), 7.31 (s, 1H), 7.46 (m, J ¼ 8.3 Hz, 1H),
7.54 (m, J ¼ 8.3 Hz, 1H), 7.76 (d, J ¼ 8 Hz, 1H), 7.90 (d,
J ¼ 8 Hz, 1H), 8.73 (s, 1H). MALDI-TOF-MS: m/z 259.5
[M þ H]þ, 281.5 [M þ Na]þ, 297.5 [M þ K]þ.
4.6 Tripodal compounds 7a–7c
To a solvent of 5 (1.00 g, 0.606 mmol) in EtOH/THF
(100/20ml) was added the solvent of NaOH (0.263g,
6.60mmol) in H2O (10 ml). The reaction mixture was stirred
overnight at 608C. After removal of EtOH/THF, we added
hydrochloric acid until acidification to a pH of 5. The
precipitated white solid was filtered and dried in vacuo. The
obtained compound 6 was obtained as a white solid and used
without further purification. To a suspension of compound 6
(296mg, 0.20mmol) in dry CH2Cl2 (40 ml) were added 2-
chloro-1-methylpyridinium iodide (204mg, 0.80mmol),
triethylamine (121mg, 1.20mmol) and H-R (0.80 mmol)
(R ¼ NHC12H25, N(C12H25)2, NHC4H9). The mixture was
stirred at 0–58C for 4 h and at room temperature for an
additional 12 h. The solvent was removed by rotary
evaporation. The residue was treated with water (50ml),
filtered and washed with water (100 ml). Products 7a–7c
were purified by silica chromatography with CHCl3 and by
recycling preparative GPC.
4.4 1,3,5-Triethyl-2,4,6-tris[2-(2-chloromethyl-1-
propenyl-3-oxy)naphthyl-3-carbamoylmethyl]benzene
(4)
Compound 2 (4.00 g, 0.15 mol) was dissolved in SOCl2
(5 ml) and heated at reflux for 4 h. The excess of SOCl2
was removed by distillation and dried in vacuo.
The remaining solid 3 was dissolved in dry THF and the
solution was maintained at 08C. To the solution were added
1,3,5-triethyl-2,4,6-trisaminomethylbenzene (1.21 g,
5.00 mmol) and Et3N (2.93 g, 0.03 mol). The mixture was
stirred overnight at room temperature and the solvent was
removed under reduced pressure. To the residue was added
water (200 ml), and the insoluble solid was separated by
filtration, and washed with water (250 ml). The residual
solid was chromatographed on silica gel with CHCl3 as an
eluent to give 4 (3.54 g, 0.354 mmol, 69%) as a yellow
1
7a (0.190 g, 48%): light yellow, H NMR (500 MHz,
CDCl3): d 0.88 (m, 9H), 1.37–1.08 (m, 60H), 2.93 (m,
9H), 3.21 (m, 6H), 4.36 (s, 6H), 4.42 (s, 6H), 4.77 (d,
J ¼ 4 Hz, 6H), 5.17 (s, 3H), 5.28 (s, 3H), 6.79 (s, 3H), 6.87
(s, 3H), 7.26 (m, 3H), 7.34 (m, 3H), 7.34 (m, 3H), 7.40 (m,
3H), 7.45 (d, J ¼ 9 Hz, 3H), 7.45 (d, J ¼ 9 Hz, 3H), 7.74
(d, J ¼ 8 Hz, 3H), 7.78 (d, J ¼ 8 Hz, 3H), 7.91 (m, 3H,
NH), 8.41 (s, 3H), 8.70 (s, 3H).
1
solid. H NMR (500 MHz, CDCl3): d 1.26 (m, 9H), 2.87
(m, 6H), 3.61 (s, 6H), 4.67 (s, 6H), 4.79 (d, J ¼ 4.5 Hz,
6H), 5.10 (s, 6H), 7.16 (s, 3H), 7.41 (m, 3H), 7.52 (m, 3H),
7.69 (d, J ¼ 8.5 Hz, 3H), 7.73 (m, 3H, NH), 7.90 (d,
J ¼ 8.0 Hz, 3H), 8.74 (s, 3H). MALDI-TOF-MS: m/z:
calcd for C60H60Cl3N3O6: 1023.35; found: 1024.03
[M þ H]þ.
1
7b (0.463g, 93%): white solid, H NMR (500MHz,
CDCl3): d 0.89 (m, 18H), 1.31 (m, 132H), 1.48 (m, 6H), 1.62
(m, 12H), 2.91 (m, 12H), 3.21 (m, 3H), 3.44 (m, 3H), 4.40
(m, 6H), 4.72 (m, 6H), 4.88 (m, 6H,), 4.94 (s, 3H), 5.505 (s,
3H), 6.89 (s, 3H), 7.23 (s, 3H), 7.31 (m, 3H), 7.34 (m, 3H),
7.34 (m, 3H), 7.37 (m, 3H), 7.55 (d, J ¼ 7.0 Hz, 3H), 7.55 (s,
3H, naphthyl), 7.59 (d, J ¼ 8.0 Hz, 3H), 7.66 (d, J ¼ 7.0 Hz,
3H), 7.84 (d, J ¼ 8.0 Hz, 3H), 7.98 (s, 3H, NH), 8.73 (s, 3H).
4.5 1,3,5-Triethyl-2,4,6-tris(2-
(methyloxycarbonylnaphthoxy)-2-propoxy-
naphthylcarbamoyl-N-methyl)benzene (5)
1
7c (0.132 g, 40%): light yellow, H NMR (500 MHz,
CDCl3): d 0.73 (m, 9H), 1.31 (m, 9H), 2.91 (m, 12H), 3.21
(m, 3H), 3.44 (m, 3H), 4.35 (m, 6H), 4.40 (m, 6H), 4.76
(m, 6H), 5.18 (s, 3H), 5.25 (s, 3H), 6.78 (s, 3H), 6.86 (s,
3H), 7.25 (m, 3H), 7.31 (m, 3H), 7.34 (m, 3H), 7.34 (m,
3H), 7.43 (m, 3H), 7.45 (m, 3H), 7.75 (d, J ¼ 8.5 Hz, 3H),
7.79 (d, J ¼ 8.5 Hz, 3H), 7.85 (s, 3H, NH), 8.42 (s, 3H),
8.70 (s, 3H).
To a solution of 2-hydroxy-3-naphthoeic acid methyl ester
(2.02 g, 0.01 mol) in 50 ml of dry DMF was added 1.2eq
NaH (0.288 g, 0.012 mol). To the stirred mixture was
added compound 4 (3.00 g, 3.00 mmol). After stirring at
608C overnight, the solvent DMF was removed under
pressure to yield yellow residue. The residue was treated
with water (200 ml) and filtered. The residual solid was
chromatographed on silica gel with CHCl3 as an eluent to
1
give 5 (3.47 g, 2.28 mmol, 76%) as a yellow solid. H
4.7 Tripodal receptors T2–T5
NMR (500 MHz, CDCl3): d 1.27 (m, 9H), 2.94 (m, 6H),
3.75 (s, 9H), 4.33 (s, 6H), 4.73 (s, 6H), 4.81 (d, J ¼ 0.4 Hz,
6H), 4.97 (s, 3H), 5.16 (s, 3H), 6.79 (s, 3H), 7.09 (s, 3H),
7.27 (m, 3H), 7.29 (d, J ¼ 8.5 Hz, 3H), 7.32 (m, 3H), 7.39
(m, 3H), 7.40 (d, J ¼ 8.5 Hz, 3H), 7.47 (d, J ¼ 8.0 Hz,
3H), 7.71 (d, J ¼ 8.0 Hz, 3H), 7.80 (m, 3H), 7.92 (m, 3H,
NH), 8.17 (s, 3H), 8.68 (s, 3H). MALDI-TOF-MS m/z:
calcd for C96H87N3O15: 1521.61; found: 1522.28
[M þ H]þ.
Compounds 7a–7c or 5 (100 mg) was dissolved in
N-methyl-2-pyrrolidone (NMP) (5 ml) and the solution
was heated at 1608C for 1 h under argon atmosphere. After
removal of NMP under reduced pressure, we purified the
residue by silica chromomatography with CHCl3 as an
eluent to give T2, T3, T4 or T5, respectively.
T2 (94 mg, 94%): yellow sticky liquid. Mp 110–
1
1128C, H NMR (500 Hz, DMSO-d6): d 0.81 (m, 9H),

Supramolecular Chemistry
327
1.28–1.15 (m, 60H), 1.56 (m, 9H), 2.96 (s, 6H), 3.85 (s,
6H), 4.20 (s, 6H), 4.86 (s, 6H), 7.29 (m, 3H), 7.32 (m, 3H),
7.42 (m, 3H), 7.42 (m, 3H), 7.67 (d, J ¼ 8.0 Hz, 3H), 7.67
(d, J ¼ 8.0 Hz, 3H), 7.74 (d, J ¼ 9.0 Hz, 3H), 7.81 (d,
J ¼ 8.5 Hz, 3H), 8.44 (s, 3H), 8.54 (s, 3H), 9.16 (m, 3H,
NH), 9.21 (m, 3H, NH), 12.77 (s, 3H, OH), 12.95 (s, 3H,
0.217 g of asymmetric isobutenyl ether derivative as a
white solid (0.310 mmol, 31%). The white solid was
heated at 1608C under vacuum for 1 h and then purified
by silica chromatography with CHCl3 as an eluent to give
L1 (0.98 g, 98%). Compound L1: light yellow solid, mp
1
60–628C, H NMR (500 MHz, CDCl3): d 0.89 (m, 3H),
OH). IR (KBr): 3401, 2924, 2853, 1633 and 1466 cm21
.
1.30 (m, 10H), 1.50 (m, 2H), 1.16 (s, 2H), 2.22 (s, 2H),
3.41 (m, 2H), 4.61 (m, 2H), 4.64 (s, 2H), 4.86 (s, 2H),
6.51 (d, J ¼ 6.5 Hz, 2H), 7.04 (s, H), 7.04 (s, H), 7.08 (s,
H), 7.2 (s, H), 7.21 (s, H), 7.26 (s, H), 7.45 (m, H), 7.45
(m, H), 7.54 (m, H), 7.54 (m, H), 7.68 (d, J ¼ 9.0 Hz, H),
7.70 (s, H), 7.70 (d, J ¼ 9.0 Hz, H), 7.92 (d, J ¼ 8.5 Hz,
H), 7.93 (d, J ¼ 8.0 Hz, H), 8.07 (s, H, NH), 8.70 (s, H),
8.79 (s, H). IR (KBr): 3413, 2922, 2811, 1690 and
Elemental analysis: Anal. Calcd for C129H156N6O12·H2O:
C, 77.44; H, 7.96; N, 4.20. Found: C, 77.41; H, 7.74; N,
4.15. MALDI-TOF-MS m/z: calcd for C165H228N6O12:
1982.65; found: 1983.91 [M þ H]þ.
T3 (93 mg, 93%): yellow sticky liquid. Mp 78–808C,
1H NMR (500 MHz, CDCl3): d 0.87 (br s, 18H), 1.02–1.67
(br s, 270H), 2.96 (br s, 6H), 3.49 (br s, 6H), 3.96 (br s,
12H), 4.40 (br s, 6H), 4.84 (br s, 6H), 7.27–7.34 (br s, 9H),
7.54–7.74 (br s, 24H), 9.16 (br s, 3H, OH), 11.95 (br s, 3H,
1454 cm21
. Elemental analysis: Anal. Calcd for
C58H78N2O4·0.5H2O: C, 79.50; H, 9.09; N, 3.20. Found:
C, 79.43; H, 9.04; N, 3.32. MALDI-TOF-MS: m/z calcd
for C58H78N2O4: 866.60; found: 889.63 [M þ Na]þ,
905.64 [M þ K]þ.
OH). IR (KBr): 3393, 2925, 2853, 1650 and 1533 cm21
.
Elemental analysis: Anal. Calcd for C165H228N6O12: C,
79.67; H, 9.24; N, 3.38. Found: C, 79.43; H, 9.66; N, 3.40.
MALDI-TOF-MS m/z: calcd for C165H228N6O12: 2485.74;
found: 2487.05 [M þ H]þ.
1
Acknowledgement
T4 (91 mg, 91%): yellow solid. Mp 134–1368C, H
One of the authors (K.H.) thanks the Ministry of Education,
Culture, Sports, Science and Technology (MEST) for partial
support through a Grant-in-Aid for Scientific Research (No.
19550132).
NMR (500 MHz, CDCl3): d 0.88 (br s, 9H), 1.32 (br s, 6H),
3.00 (br s, 6H), 3.26 (br s, 6H), 3.79 (br s, 6H), 3.88 (br s,
6H), 4.27 (m, 6H), 4.84 (s, 6H), 6.46 (br s, 3H), 6.76 (br s,
3H), 7.01 (br s, 3H), 7.16 (br s, 3H), 7.31 (br s, 9H), 7.56
(br s, 9H), 7.71 (d, J ¼ 8.0 Hz, 3H), 7.79 (s, 3H), 11.87 (br
s, 6H, OH). IR (KBr): 3409, 2908, 1690 and 1447 cm21
.
References
Elemental analysis: Anal. Calcd for C105H108N6O12: C,
76.62; H, 6.61; N, 5.11. Found: C, 76.89; H, 6.43; N, 4.84.
MALDI-TOF-MS m/z: calcd for C105H108N6O12: 1646.01;
found: 1647.62 [M þ H]þ.
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T5 (96 mg, 96%) white solid. Mp 152–1548C. 1H
NMR (CDCl3, 500 MHz): d 1.36 (m, 9H), 2.91 (m, 6H),
3.98 (s, 12H), 4.00 (s, 9H), 4.40 (s, 6H), 4.80 (s, 6H), 6.42
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4.8 Compound L1
1,3-Bis[2-(3-chlorocarbonyl) naphthoxy]-2-methylene-
propane[3a] (0.465 g, 1.00 mmol) was added to the
50 ml THF solution of p-methylbenzylamine (0.185 g,
1.00 mmol) and stirred at room temperature for 4 h. Then,
N-dodecylamine (0.740 g, 4.00 mmol) was added to the
mixture and stirred overnight at room temperature. THF
was evaporated and water was added into the residue to
give a solid. The solid was subjected to column
chromomatography on silica gel with CHCl3 as an eluent
and then separated by recycling preparative GPC to give

328
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