A color version of the Hinsberg test: permethylated cyclodextrin and crown-appended azophenol for highly selective sensing of amines

Article abstract of DOI:10.1016/j.tet.2008.05.013

Azophenol dyes 1-5 having the permethylated cyclodextrin and/or crown moieties have been synthesized. Compounds 1 and 2 provide critical information for discrimination among 1°-3° amines by unique color changes. Addition of 1° and 2° amines to solutions o

Full text of DOI:10.1016/j.tet.2008.05.013

Tetrahedron 64 (2008) 6705–6710
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
A color version of the Hinsberg test: permethylated cyclodextrin
and crown-appended azophenol for highly selective sensing of amines
,
a
a
a
b
b,
*
Jong Hwa Jung a , Hye Young Lee , Sung Ho Jung , Soo Jin Lee , Yoshiteru Sakata , Takahiro Kaneda
*
a Department of Chemistry, Research Institute of Natural Science, Gyeongsang National University, Jinju 660-701, South Korea
b Institute of Scientific and Industrial Research, Osaka University, Osaka 569-0047, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Azophenol dyes 1–5 having the permethylated cyclodextrin and/or crown moieties have been synthe-
sized. Compounds 1 and 2 provide critical information for discrimination among 1ꢀ–3ꢀ amines by unique
color changes. Addition of 1ꢀ and 2ꢀ amines to solutions of 1 or 2 in chloroform shifts the absorbance
maximum of the initial solutions from 380 nm to w580 nm and w530 nm, respectively, but no change is
observed with 3ꢀ amines. The high selectivity of 1 is mainly due to H-bonding between the ammonium H
Received 21 March 2008
Received in revised form 1 May 2008
Accepted 1 May 2008
Available online 7 May 2008
atoms of the amine and oxygen atoms of the crown-6. The selectivity of 1 possessing the
b-cyclodextrin
Keywords:
Alanines
Amphiphiles
Helical ribbons
Self-assembly
moiety toward amines was higher than that of 2 possessing the -cyclodextrin moiety. On the other
a
hand, chloroform solutions of 3 or 4, which lack the crown ether moiety, changed from yellow (380 nm)
to pink (500 nm) with the addition of 1ꢀ and 2ꢀ amines, but with no selectivity. These results indicate
that the crown unit in 1 or 2 plays an important role in discriminating among the types of amines.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
amines with regard to the color changes, we report here unique
chemosensors 1 and 2 (Scheme 1), which are capable of exhibiting
Amines and ammonia are used for the preparation of colorants,
medicines, surfactants, catalysts, pesticides, polymers, etc. These
compounds are toxic both in the gas phase and when dissolved in
liquids. A variety of sensors have been developed for their de-
termination in environmental, industrial, food, biological, and
clinical samples. The detection of amines based on optical-sensing
methods can be based on pH indicator dyes, solvatochromic dyes,1
metal complexes,2 organic reactions,3 chromophores,4 etc. Among
the methods for the detection of amines is the Hinsberg test,5 based
on an organic reaction, which forms characteristic base-soluble
sulfonamides. Developed more than 100 years ago and well docu-
mented in textbooks, the Hinsberg test can be used to discriminate
among 1ꢀ–3ꢀ amines. Recently, many functional host molecules
such as cyclodextrins,6 calix[4]arenes,7 and crown ethers, based on
coordinative or hydrogen-bonding interactions as the main driving
force, have been reported as reagents for the detection of amines.
For amine recognition, macrocyclic polyethers have been shown
to bind primary ammonium ions by anchoring the R–NHþ3 group
into their circular cavity via three H-bonds (N–H/O).8–11 However,
the selective recognition toward specific alkylamines has not been
achieved due to the lack of selectivity. By overcoming the low
selectivity and low sensitivity for the discrimination of types of
selective color changes toward 1ꢀ–3ꢀ amines, and may be viewed as
the color version of the Hinsberg test.
2. Results and discussion
Syntheses of compounds 1, 2, and 5 are summarized in Scheme
1. Permethylated
ted with 2,6-bis(bromomethyl)-1,4-dimethoxybenzene to yield the
corresponding permethylated -cyclodextrin ( -CD) and -cyclo-
dextrin ( -CD) in 75% and 80% yields, respectively. 2-(Hydrox-
ylmethyl)-18-crown-6 was reacted with permethylated - or
-CD-appended-bromomethyl-1,4-dimethoxybenzene (16 or 17) to
give the corresponding asymmetric permethylated - or -cyclo-
dextrin in 50% and 65% yields, respectively. Then, after the oxidation
of 18-crown-6-appended permethylated -CD or -CD with cer-
a- or b
-cyclodextrin-6-monoalcohol12 was reac-
a
a
b
b
a
b
a
b
a
b
ium(IV) ammonium nitrate (CAN), treatment with p-nitro-
phenylhydrazine gave the desired 1 and 2 in 45% and 30% yields,
respectively. Compounds 4 and 5 were also synthesized in 20% and
25% yields by similar methods as used for 1, respectively. Com-
pounds 3 and 4 were prepared byadaptation of procedures reported
earlier.12,13 The structures of 1–5 were confirmed by 1H NMR,
MALDI-TOF mass spectroscopy, and elemental analysis (Fig. 1).
The binding behaviors of 1–5 toward various amines were in-
vestigated by UV–vis spectrophotometry. Association constants14
were also determined from the UV–vis band changes upon the
addition of 1ꢀ–3ꢀ amines to chloroform solutions of 1–5 and are
* Corresponding authors. Tel.: þ82 55 751 6027; fax: þ82 55 758 6027.
E-mail address: jonghwa@gnu.ac.kr (J.H. Jung).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.05.013

6706
J.H. Jung et al. / Tetrahedron 64 (2008) 6705–6710
R1
O
Br
OH
R1
O
O
R2
O
8 :R1= -CD,(OMe)20
9 :R1= -CD,(OMe)17
10 :R1=p–chlorophenol
11 :R1= -CD,(OMe)20, R2=18-crown-6
12 :R1= -CD,(OMe)17, R2=18-crown-6
13 :R1=p–chlorophenol, R2=18-crown-6
6 : -CD,(OMe)20
7 : -CD,(OMe)17
R1 OH R2
R1
O
O
R2
N
N
NO2
14 : R1= -CD,(OMe)20, R2=18-crown-6
15 : R1= -CD,(OMe)17, R2=18-crown-6
16 : R1=p–chlorophenol, R2=18-crown-6
1 : R1= -CD,(OMe)20, R2=18-crown-6
2 : R1= -CD,(OMe)17, R2=18-crown-6
5 : R1=p–chlorophenol, R2=18-crown-6
Scheme 1. Synthetic method of compounds 1, 2, and 5.
O
O
O
O
O
O
O
O
O
O
O
O
O
OH
O
O
OH
N
O
O
OH O
N
N
N
N
N
NO2
NO2
NO2
1
2
3
O
O
O
O
O
O
O
OH
O
Cl
O
OH
O
N
N
N
N
NO2
NO2
5
4
Figure 1. Chemical structures of 1–5.

J.H. Jung et al. / Tetrahedron 64 (2008) 6705–6710
6707
Table 1
b
-CD, which can interact with the lipophilic alkyl chain of the
a
Association constants and pKa of the ligands 1–5 for various amines in CHCl3
amine by a hydrophobic interaction (vide infra). On the other hand,
addition of 3ꢀ amines to 1 gave no color change. The lack of color
change of 1 toward 3ꢀ amines is presumably due to a steric hin-
drance between the alkyl chain of the 3ꢀ amine and the
b-CD.
The color change of 2 upon the addition of amines was quite
similar to that of 1 (Fig. 3 and Fig. S2 (Supplementary data)).
However, bathochromic shifts of 2 with 1ꢀ and 2ꢀ amines were
slightly smaller than those of 1. The reason for this lesser shift is not
clear. It may be attributed to steric hindrance between the
moiety and alkyl chain of amine, despite the fact that the binding
affinity of the -CD for alkylamines is much stronger than that of
the
-CD.16,17
To gain an insight into the role of the hydrophobic interaction
Amine
1
2
3
4
5
n-Propylamine
n-Butylamine
n-Pentylamine
n-Hexylamine
n-Heptylamine
n-Octylamine
n-Decylamine
1,7-Diaminoheptane
Di-n-ethylamine
Di-n-propylamine
Di-n-butylamine
Di-n-hexylamine
Di-n-octylamine
Di-n-decylamine
Di-n-methyldiaminohexane
2,6-Dimethyl-piperidine
pKa
4.6
4.45
4.6
4.55
4.3
4.3
4.7
4.85
4.19
2.1
2.11
2.32
2.14
2.17
2.2
2.01
2.04
1.78
1.62
1.57
1.81
1.78
1.72
2.02
1.93
1.83
1.76
1.77
1.85
1.7
1.71
1.79
1.62
1.59
1.57
1.75
1.76
1.67
1.81
1.75
1.72
1.74
1.75
1.8
2.04
2.09
1.99
2.05
2.01
2.12
2.15
2.05
1.53
1.47
1.46
1.46
1.45
1.5
4.72
4.59
4.45
4.47
4.85
4.95
4.25
2.35
2.23
2.48
2.2
a-CD
a
b
2.19
2.37
2.11
2.1
between the CD moiety and the alkyl chain of amine, we measured
1H NMR spectrum of 2 upon the addition of the amine. The NMR
spectrum of the 1$n-heptylamine complex (Fig. S3 (Supplementary
data)) showed that the protons of the crown loop and C1–H of the
2.05
2.02
5.75
1.65
1.74
5.99
1.31
1.41
7.30
1.75
5.91
5.45
a
The Ka [Mꢁ1] values were obtained by using the ENZFITTER program based on
a
-CD underwent a high-field shift. This observation is consistent
the 1:1 complexation phenomena between receptor and respective amines.
with the formation of H-bonds between the H atoms of the am-
monium and the crown ring of 2 as well as with the development of
hydrophobic interactions with the target amine.
listed in Table 1 and Table S1 (Supplementary data). Among these
receptors, 1 responded markedly to the 1ꢀ and 2ꢀ amines, exhib-
iting distinct color changes from orange (complementary to the
absorption of 380 nm) to blue (complementary to the absorption of
580 nm, Figs. 2 and 3 and Fig. S1 (Supplementary data)) for 1ꢀ
amines and red (complementary to the absorption of 510 nm, Figs.
2 and 3, and Fig. S1 (Supplementary data)) for 2ꢀ amines, with an
isosbestic point at 439 nm. This bathochromic shift is caused by the
amine based-deprotonation of the azophenol, inducing a photo-
induced charge transfer (PCT).15 In addition, the selectivity of 1
toward the type of amines is closely related to comparable
H-bonding interactions between the crown ring of 1 and the pro-
tons of the ammonium ion as well as to a critical role of the adjacent
Upon addition of n-octylamine, the intensity of the w380 nm
absorption band of 1 and 2 decreased with concomitant increase of
a new band centered at w580 nm with only one isosbestic point at
w460 nm, providing solid evidence of formation of a 1:1 complex
(Figs. S1 and S4 of Supplementary data). To confirm the complex-
ation ratio, we performed FAB mass spectroscopy for the
2$n-heptylamine complex. A 1:1 complexation ratio (1886.12 m/e,
Fig. 4) is evident for 2$n-heptylamine complex.
The log Ka values of 1 for 1ꢀ and 2ꢀ amines are 4.25–4.95 and
2.10–2.48, respectively, as listed in Table 1. The selectivity of 1 be-
tween 1ꢀ and 2ꢀ amines was calculated to be 60–720. These results
also indicate that the number of H-bonds formed between the
Figure 2. (A) UV–vis spectra and (B) photograph of 1 with amines in CHCl3: (a) 1, (b) 1þn-octylamine (1000 equiv), (c) 1þdi-n-butylamine (1000 equiv), and (d) 1þtri-n-butylamine
(1000 equiv).
Figure 3. Absorption maxima of 1–5 with amines (1000 equiv) in chloroform.

6708
J.H. Jung et al. / Tetrahedron 64 (2008) 6705–6710
selectivity of 5 toward the tested amines were much lower than
those of 1 and 2. Therefore, the less selective interaction and low
sensitivity are related to the hydrophobic interaction between the
CD moiety and the alkyl chain of the amine. A single isosbestic
point appeared in the spectrum of 5 with n-octylamine in CHCl3,
indicating the formation of a 1:1 complex (Fig. S11 of Supplemen-
tary data).
Acidity, pKa, is also an important determinant of the selectivity
and sensitivity of the acidic ligands toward the target guest mole-
cules. The pKa values of azophenols 1–5 in solutions of H2O/1,4-
dioxane (9:1 v/v) were determined to be in the range from 5.45 to
–7.30. The pKa value of 1 was much higher than those of 2–5 and
thus, the sensitivity of 1 toward amines greatly exceeded that of
compounds 2–5. It is noteworthy that 1 and 2 can be easily
deprotonated to give rise to the phenoxide anion, which develops
the photo-induced charge transfer through the p-nitrodiazophenol
to provide its bathochromic shift.
According to UV–vis, NMR, and mass spectra of the complex, we
proposed the complex structures of 1$amine or 2$amine in Fig-
ure 5. Previously Kaneda et al., investigating the H-bonding in-
teractions between the crown ring of a macrocyclic chromophore
and amines through XRD study,16,17 reported that 1ꢀ amines formed
three-pointed perching H-bonds between the oxygen atoms of 18-
crown-6 and the H atoms of the ammonium ion while a 2ꢀ amine
participated only through two-pointed H-bonding interaction.
Figure 4. FAB mass spectrum of 2þn-heptylamine (1000 equiv) in CHCl3.
crown ring of 1 and the protons of the ammonium ion is of critical
importance for discrimination between the amines. The log Ka of 2
with amines is slightly smaller than that of 1. We think that the
slightly smaller log Ka is probably due to the steric hindrance be-
tween 6-methyl groups of permethylated a-CD and the alkyl chain
of amine. Also, the log Ka is dependent on the acidity (pKa) of 1 or 2.
In conclusion, probably the slightly smaller log Ka of 2 with primary
amines is probably due to the two factors (steric hindrance and pKa)
mentioned above.
Compounds 3 and 4, which contained no 18-crown-6 ether
moiety, were synthesized to investigate the influence of the crown
unit on the amine selectivity. Unlike the case of 1, addition of 1ꢀ and
2ꢀ amines to the chloroform solutions of 3 or 4 changed the color
from yellow (380 nm) to pink (500 nm) (Table S1 and Figs. S5–S8 of
Supplementary data, respectively), but with no selectivity. On the
other hand, addition of 3ꢀ amines to 3 or 4 gave no color change.
Thus, the crown unit in 1 or 2 plays an important role in discrim-
inating among the types of amines.
By utilizing
a competition experiment, we measured the
changes of the absorption intensity upon the addition of the 1ꢀ
amine (n-propylamine) to the chloroform solution of 1 containing
2000 equiv of the 3ꢀ amine (triethylamine). Addition of even
a small amount of the n-propylamine under these conditions
resulted in a marked increase in absorption intensity at 585 nm
(Fig. 6). In the reverse case, after addition of 3ꢀ amine to the solu-
tion (1þ1ꢀ alkylamine), no spectral changes were observed. These
findings predict that 1 could selectively recognize a 1ꢀ amine, even
in the presence of an excess of 3ꢀ amine.
3. Conclusions
In addition, 5 with a p-chlorophenyl unit instead of the CD was
prepared to elucidate the role of the CD in the amine selectivity.
Addition of 1ꢀ and 2ꢀ amines to the chloroform solution of 5
changed the color from yellow (lmax¼380 nm) to pale blue
Amine receptors based on CD/18-crown-6-appended azophenol
(compounds 1 and 2) were synthesized. The main factors contrib-
uting to the high selectivity of 1 and 2 toward amines are: (i) the
formation of efficient H-bond interactions between the oxygen
atoms of the crown loop and the H atoms of the ammonium ion of
the amines; (ii) the hydrophobic interaction between the CD and
the lipophilic tail of the amine; and (iii) the acidity of the host
(
lmax¼w560 nm) and to pink (lmax¼w540 nm), respectively, with
an isosbestic point at 445 nm (Table S1 and Figs. S9–S11 of (Sup-
plementary data). As with 1, no color change was noted with the
addition of 3ꢀ amines. However, both binding affinity and
O
O
R''
O
O
R'
R'
O
O
O
O
O
O
O
O
O
H
H
β
H
O
β
H
O
β
H
O
N
R
R
N
R
N
O
O
H
O
O
N
O
O
O
N
O
O
O
O
N
N
N
N
NO2
NO2
NO2
(a)
(c)
(b)
Figure 5. Proposed structures for complex formation of 1 with (a) 1ꢀ amine, (b) 2ꢀ amine, and (c) 3ꢀ amine.

J.H. Jung et al. / Tetrahedron 64 (2008) 6705–6710
6709
(b)
(a)
0.5
0.4
0.3
0.2
0.1
0.0
0.4
1,500eq
1,250eq
1,000eq
600eq
320eq
1 only
0.2
0.0
400
500
Wavelength (nm)
600
700
0
500 1000 1500
[amine]/[1]
Figure 6. Wavelength changes of 1 (0.03 mM) upon the addition of n-octylamine in the presence of triethylamine (2000 equiv) in CHCl3.
molecule. Hence, molecules 1 and 2 reported here can be consid-
ered as an innovative tool in the discrimination of the 1ꢀ–3ꢀ
amines. This simple and straightforward qualitative analysis, using
the synthesized novel compounds herein, can be considered
a new innovative tool for discriminating 1ꢀ–3ꢀ amines as an alter-
native to the historical Hinsberg test.
(2.0 g, 6.17 mmol) in dry THF (80 mL) was slowly added to a sus-
pension of NaH (6.7 g) in dry THF (20 mL), and the reaction mixture
was refluxed for overnight. After the reaction mixture was cooled to
0 ꢀC, a small portion of chilled water was added to the reaction
mixture to quench the excess NaH. The solvent was removed under
reduced pressure and the residue was extracted with CHCl3. The
combined extracts were washed with water, dried over MgSO4, and
concentrated under reduced pressure. Purification by LC (eluting
with chloroform) provided 0.45 g of 10 in 20% yield. Mp 159.7 ꢀC.
4. Experimental
4.1. Synthesis
FTIR (KBr): 3012, 2985, 1580, 1520, 1475, 1050 cmꢁ1 1H NMR
.
(270 MHz, CDCl3): 6.98–6.80 (m, 6H), 5.14 (s, 2H), 4.34 (s, 2H), 3.84
Compounds 6 and 7 were prepared by adaptation of procedures
(s, 3H), 3.70 (s, 3H). MS (m/z): 393 [MþNaþ]. Anal. Calcd for
previously reported.12,13
C16H16ClBrO3: C, 51.71; H, 4.34; Cl, 9.54; Br, 21.50. Found: C, 52.00;
H, 4.37; Cl, 9.52; Br, 21.51.
4.2. Compound 8
4.5. Compound 11
Under N2 atmosphere, a solution of 6 (0.5 g, 0.412 mmol) and
2-bis(bromomethyl)-1,4-dimethoxybenzene (0.4 g, 1.23 mmol) in
dry THF (10 mL) was slowly added to a suspension of NaH (0.138 g)
in dry THF (1 mL), and the reaction mixture was refluxed for 21 h.
After the reaction mixture was cooled to 0 ꢀC, a small portion of
chilled water was added to the reaction mixture to quench the
excess NaH. The solvent was removed under reduced pressure and
the residue was extracted with CHCl3. The combined extracts were
washed with water, dried over MgSO4, and concentrated under
reduced pressure. Purification by LC (eluting with methanol) pro-
vided 0.32 g of 8 in 75% yield. Mp 102.7 ꢀC. FTIR (KBr): 3015, 2980,
1585,1521, 1480,1047 cmꢁ1. 1H NMR (270 MHz, CDCl3): 6.90 (s, 1H),
6.82 (s, 1H), 5.09–5.04 (m, 7H), 4.78 (d, 2H), 4.72 (s, 2H), 3.82–3.15
Under N2 atmosphere, a solution of 8 (0.4 g, 0.24 mmol) and (2-
hydroxymethyl)18-crown-6 (0.14 g, 0.417 mmol) in dry THF (3 mL)
was slowly added to a suspension of NaH (0.16 g, 4.17 mmol) in dry
THF (1 mL), and the reaction mixture was refluxed for 20 h. After
the reaction mixture was cooled to 0 ꢀC, a small portion of chilled
water was added to the reaction mixture to quench the excess NaH.
The solvent was removed under reduced pressure and the residue
was extracted with CHCl3. The combined extracts were washed
with water, dried over MgSO4, and concentrated under reduced
pressure. Purification by LC (eluting with methanol) gave 11 in
66.7% yield. Mp 115.2 ꢀC. FTIR (KBr): 3015, 2982, 1585, 1510, 1473,
1048 cmꢁ1 1H NMR (270 MHz, CDCl3): 6.92 (s, 1H), 6.85 (d, 1H),
.
(m, 108). MS (m/z): 1678.7 [MþNaþ]. Anal. Calcd for C72H121BrO37
:
5.08–5.04 (m, 7H), 4.62 (d, 2H), 4.51 (s, 2H), 3.80–3.11 (m, 133H).
C, 52.14; H, 7.35. Found: C, 53.07; H, 7.21.
FABMS (m/z): 1893.0 [Mþm-nitrobenzoic acid]. Anal. Calcd for
C85H146O44: C, 54.53; H, 7.86. Found: C, 53.05; H, 7.95.
4.3. Compound 9
4.6. Compound 12
Compound 9 was prepared by a similar method as mentioned
above in 75% yield. Mp 102.7 ꢀC. FTIR (KBr): 3010, 2983, 1579, 1520,
Yield: 50%. Mp 110.5 ꢀC. FTIR (KBr): 3010, 2980, 1587, 1520, 1480,
1050 cmꢁ1. 1H NMR (270 MHz, CDCl3): 6.80 (s, 2H), 5.09–5.04 (m,
6H), 4.82 (d, 2H), 4.73 (s, 2H), 3.82–3.15 (m, 118H). MS (m/z): 1697
[MþNaþ]. Anal. Calcd for C76H130O39: C, 54.73; H, 7.86. Found: C,
54.70; H, 7.85.
1480, 1045 cmꢁ1 1H NMR (270 MHz, CDCl3): 6.91 (s, 1H), 6.80 (s,
.
1H), 5.09–5.04 (m, 6H), 4.82 (d, 2H), 4.73 (s, 2H), 4.73 (s, 2H), 3.82–
3.15 (m, 91). MS (m/z): 1475 [MþNaþ]. Anal. Calcd for C63H105BrO32
:
C, 52.03; H, 7.28. Found: C, 53.05; H, 7.20.
4.4. Compound 10
4.7. Compound 13
Under N2 atmosphere, a solution of p-chlorophenol (0.63 g,
4.90 mmol) and 2-bis(bromomethyl)-1,4-dimethoxybenzene
Yield: 70%. Mp 150.2 ꢀC. FTIR (KBr): 3012, 2983, 1581, 1515, 1472,
1050 cmꢁ1 1H NMR (270 MHz, CDCl3): 7.00–6.80 (m, 6H), 5.17 (s,
.

6710
J.H. Jung et al. / Tetrahedron 64 (2008) 6705–6710
2H), 4.30 (s, 2H), 3.80 (s, 3H), 3.70–3.20 (m, 28H). MS (m/z): 607.2
[MþNaþ]. Anal. Calcd for C29H41ClO10: C, 59.53; H, 7.06; Cl, 6.06; Br,
27.35. Found: C, 59.00; H, 7.07; Cl, 6.12.
4.13. Compound 3
Compound 3 was prepared as described previously. Mp 20ꢁ51–
207 ꢀC. FTIR (KBr): 3253, 3010, 2973, 1585, 1521, 1485, 1050 cm
.
4.8. Compound 14
1H NMR (270 MHz, CDCl3): 8.37 (d, 2H), 8.35 (s, 1H), 7.96 (d, 2H),
7.86 (s, 2H), 5.08 (m, 7H), 4.95–4.82 (dd, 4H), 3.82–3.15 (m, 212H).
MS (m/z): 3130.5 [MþNaþ]. Anal. Calcd for C138H229O73N3: C, 53.50;
H, 7.45; N, 1.36. Found: C, 53.87; H, 7.41; N, 1.35.
A solution of 13 (0.36 g, 0.79 mmol) in CH3CN (1 mL) was added
to a solution of ceric ammonium nitrate (0.340 g, 0.79 mmol) in
CH3CN (1 mL) and H2O (0.5 mL). The mixture was then stirred for
2 h at room temperature. After the reaction mixture was cooled to
0–5 ꢀC, water was added to the mixture. The mixture was extracted
with CHCl3 and the combined extracts were washed with water,
dried over MgSO4, and concentrated under reduced pressure.
Purification by LC (eluting with methanol) gave 14 in 85% yield. Mp
4.14. Compound 4
Compound 4 was prepared as described previously.6 Mp 19ꢁ91–
200 ꢀC. FTIR (KBr): 3250, 3015, 2980, 1585, 1520, 1485, 1050 cm
.
1H NMR (270 MHz, CDCl3): 8.37 (d, 2H), 8.34 (s, 1H), 7.97 (d, 2H),
7.86 (s, 2H), 5.08 (m, 6H), 4.95–4.82 (dd, 4H), 3.82–3.15 (m, 196H).
MS (m/z): 2917.3 [MþNaþ]. Anal. Calcd for C129H213O68N3: C, 53.54;
H, 7.42; N, 1.45. Found: C, 53.87; H, 7.41; N, 1.39.
115.6 ꢀC. FTIR (KBr): 3015, 2980, 1640, 1582, 1517, 1480, 1050 cmꢁ1
.
1H NMR (270 MHz, CDCl3): 6.75 (s, 1H), 6.57 (s, 1H), 5.05 (m, 7H),
4.47 (s, 2H), 4.25 (s, 2H), 3.85–3.14 (m, 129H). MS (m/z): 1849.9
[MþNaþ]. Anal. Calcd for C83H140O44: C, 54.12; H, 7.66. Found: C,
54.25; H, 7.55.
4.15. Compound 5
4.9. Compound 15
Yield: 21%. Mp 125.5 ꢀC. FTIR (KBr): 3225, 3017, 2985,1730,1585,
1520, 1480, 1450, 1050 cmꢁ1 1H NMR (270 MHz, CDCl3): 8.37 (d,
.
Yield: 52%. Mp 107.6 ꢀC. FTIR (KBr): 3020, 2985, 1650, 1587, 1517,
1480, 1050 cmꢁ1. 1H NMR (270 MHz, CDCl3): 6.48 (s, 2H), 5.10–5.03
(m, 6H), 4.82 (d, 2H), 4.73 (s, 2H), 3.82–3.15 (m, 112H). MS (m/z):
1660 [MþNaþ]. Anal. Calcd for C74H124O39: C, 54.27; H, 7.63. Found:
C, 54.25; H, 7.55.
2H), 8.17 (s, 1H), 7.97 (d, 2H), 7.72 (s, 2H), 7.23 (d, 2H), 6.96 (d, 2H),
5.22 (s, 2H), 4.92 (s, 2H), 3.95–3.52 (br m, 25H). MS (m/z): 711
[MþNaþ]. Anal. Calcd for C33H40O11N3Cl: C, 57.43; H, 5.84; N, 6.09;
Cl, 5.14. Found: C, 56.95; H, 5.60; N, 6.02; Cl, 5.20.
Acknowledgements
4.10. Compound 16
This work was supported by Korea Research Foundation Grant
(KRF-2005-070-C00068) and KOSEF (2008-01014).
Yield: 65%. Mp 145.5 ꢀC. FTIR (KBr): 3010, 2985, 1635, 1588, 1517,
1472, 1050 cmꢁ1. 1H NMR (270 MHz, CDCl3): 7.10–6.85 (m, 6H), 5.15
(s, 2H), 4.30 (s, 2H), 3.78 (s, 3H), 3.80–3.15 (m, 28H). MS (m/z): 577.5
[MþNaþ]. Anal. Calcd for C27H35ClO10: C, 58.43; H, 6.36; Cl, 6.39.
Found: C, 58.45; H, 6.35; Cl, 6.35.
Supplementary data
UV–vis spectra of 1–5 with amines in CHCl3. Photographs for
color changes of 2–5 with amines. Supplementary data associated
with this article can be found in the online version, at doi:10.1016/
j.tet.2008.05.013.
4.11. Compound 1
To a solution of 14 (0.13 g, 0.070 mmol) in EtOH (1 mL), a solu-
tion of (4-nitrophenyl)hydrazine (0.022 g, 0.14 mmol) and two
drops of concd H2SO4 in EtOH (1 mL) were added. The reaction
mixture was allowed to stir overnight. The mixture was extracted
with CHCl3 and the combined extracts were washed with water,
dried over MgSO4, and concentrated under reduced pressure. Pu-
rification by LC (eluting with methanol) gave 0.03 g of 1 in 25%
yield. Mp 125.7 ꢀC. FTIR (KBr): 3020, 2985, 1730, 1587, 1517, 1480,
References and notes
1. Fiorilli, S.; Onida, B.; Macquarrie, D.; Garrone, E. Sens. Actuators, B 2004, 100,
103.
2. Absalan, G.; Soleimani, M.; Asadi, M.; Ahmadi, M. Anal. Sci. 2004, 20, 1433.
3. Lau, K.; Edwards, S.; Diamond, D. Sens. Actuators, B 2004, 98, 12.
4. Mohr, G.; Demuth, G.; Spichiger-Keller, U. Anal. Chem. 1998, 70, 3868.
5. Hinsberg, O. Chem. Ber. 1890, 23, 2962.
6. Jung, J. H.; Lee, S. J.; Kim, J. S.; Lee, W. S.; Sakata, Y.; Kaneda, T. Org. Lett. 2006, 8,
3009.
7. Kim, J. S.; Lee, S. J.; Jung, J. H.; Hwang, I.-C.; Singh, N. J.; Kim, S. K.; Lee, S. H.; Kim,
H. J.; Keum, C. S.; Lee, J. W.; Kim, K. S. Chem.dEur. J. 2007, 13, 3082.
8. Cram, D. J.; Cram, J. M. Acc. Chem. Res. 1978, 11, 8.
9. Stoddart, J. F. Chem. Soc. Rev. 1979, 8, 85.
10. Mock, W. L.; Shih, N.-Y. J. Org. Chem. 1986, 51, 4440.
11. Hayward, R. C. Chem. Soc. Rev. 1983, 12, 285.
12. Jung, J. H.; Takehisa, C.; Sakata, Y.; Kaneda, T. Chem. Lett. 1996, 147.
13. Fujimoto, T.; Uejima, Y.; Imaki, H.; Kawarabayashi, N.; Jung, J. H.; Sakata, Y.;
Kaneda, T. Chem. Lett. 2000, 564.
14. Connors, K. A. Binding Constants; Wiley: New York, NY, 1987.
15. Cobben, P. L. H. M.; Egberink, R. J. M.; Bomer, J. G.; Bergveld, P.; Verboom, W.;
Reinhoudt, D. N. J. Am. Chem. Soc. 1992, 114, 10573.
1450, 1050 cmꢁ1 1H NMR (270 MHz, CDCl3): 8.47 (s, 1H), 8.37 (d,
.
2H), 7.95 (d, 2H), 7.86 (s, 1H), 7.84 (s, 1H), 5.22–5.10 (m, 7H), 4.82 (s,
2H), 4.73 (s, 2H), 3.82–3.15 (m, 127H). MS (m/z): 1998.5 [MþNaþ].
Anal. Calcd for C89H145O45N3: C, 54.04; H, 7.39; N, 2.13. Found: C,
54.28; H, 7.18; N, 2.07.
4.12. Compound 2
Yield: 30%. Mp 115.7 ꢀC. FTIR (KBr): 3020, 2985, 1730, 1587, 1517,
1480, 1450, 1050 cmꢁ1. 1H NMR (270 MHz, CDCl3): 8.47 (s, 1H), 8.37
(d, 2H), 7.95 (d, 2H), 7.85 (s, 2H), 5.09–5.04 (m, 6H), 4.82 (d, 2H),
4.73 (s, 2H), 3.82–3.15 (m, 112H). MS (m/z): 1795 [MþNaþ]. Anal.
Calcd for C80H129O40N3: C, 54.20; H, 7.33; N, 2.37. Found: C, 51.95; H,
7.20; N, 2.22.
16. Kaneda, T. Crown Ethers and Analogous Compound; Hiraoka, M., Ed.; Elsevier:
New York, NY, 1992; Chapter 6.
17. Kaneda, T.; Umeda, S.; Ishizaki, Y.; Kuo, H.-S.; Misumi, S.; Kai, Y.; Kanehisa, N.;
Kasai, N. J. Am. Chem. Soc. 1989, 111, 1881.