3764 J . Org. Chem., Vol. 61, No. 11, 1996
Kubo et al.
of Na+, K+, Mg2+, and Ca2+ caused a bathochromic shift
as if only Ca2+ was added to the solution of 7. The high
preference of ligand 7 for Ca2+ can be attributed to the
better fitting of Ca2+ inside the pocket formed by the
quinone carbonyl groups of the chromophores and (ethoxy-
carbonyl)methoxy groups and to the enhanced electro-
static interactions between Ca2+ and oxygens involved
in complexation.
materials obtained were filtered, dried in vacuo, and chro-
matographed on silica gel (Wakogel C-300) using CHCl3-
(CH3)2CO (50:1 v/v) as eluent to provide 17 mg of mono-
(indoaniline)-derived 3 (2% yield), 228 mg of 1,2-bis(indoaniline)-
derived 4 (25% yield), 316 mg of 1,3-bis(indoaniline)-derived
5 (35% yield), and a small amount of tetrakis(indoaniline)-
derived calix[4]arene 6 (trace), respectively.
23-((4′-(Dieth ylam in o)-2′-m eth ylph en yl)im in o)-26,27,28-
t r i h y d r o x y p e n t a c y c l o [ 1 9 .3 .1 3 , 7 .1 9 , 1 3 .1 1 5 , 1 9 ] o c t a -
cosa -1(24),3,5,7(28),9,11,13(27),15,17,19(26),21-u n d eca en -
1
25-on e (3): mp 231-233 °C; H NMR (CDCl3) δ 1.18 (t, J )
Su m m a r y
7.0 Hz, 6H), 2.28 (s, 3H), 3.39 (q, J ) 7.0 Hz, 4H), 3.52-4.00
(brd, 8H), 6.47 (dd, J ) 2.7, 9.6 Hz, 1H), 6.53 (s, 1H), 6.56-
6.65 (m, 4H), 6.78 (d, J ) 6.9 Hz, 1H), 6.91-6.98 (m, 5H), 7.19
(s, 2H), 9.38-9.68 (brd, 2H), 9.68-9.91 (brd, 1H); FTIR (KBr)
1595; mass spectrum m/ z 600 (M+ + 2). Anal. Calcd for
C39H38N2O4: C, 78.24; H, 6.40; N, 4.68. Found: C, 78.09; H,
6.44, N; 4.61.
A new type of 1,3-bis(indoaniline)-derived 2,4-bis-
((ethoxycarbonyl)methoxy)calix[4]arene (7), prepared by
1 with 2 and followed by ethoxycarbonylmethylation, is
the first rationally designed chromogenic calixarene-type
receptor for Ca2+ and is more sensitive to Ca2+ than to
Na+, K+, and Mg2+, making it of potential use as an
optical sensor for Ca2+ detection. The IR and NMR
studies indicate that Ca2+ can be encapsulated in the
cavity made by the distally located OCH2CO2 groups on
the lower rim of cone-shaped calix[4]arene segment. On
the other hand, 1,2-bis-substituted analogue 8 shows no
response with those metal ions, which may be interpreted
by no cavity on the lower rim of calixarene. We believe
that this type of chromogenic receptor possessing a
calixarene unit as a recognition site and indoaniline
chromophore as an optical sensing site is of great value
because it has synthetic advantage as follows: (1) the
introduction of the chromophore into a calixarene skel-
eton is convenient; (2) several chemical modifications by
some functional groups on the calixarene framework lead
to change the shape of cavity, so that it would encapsu-
late various guest species. In our laboratory, the design,
development, and elucidation of other types of chromo-
genic receptors according to this concept are in
progress.6e,9f,h
17,23-Bis((4′-(d iet h yla m in o)-2′-m et h ylp h en yl)im in o)-
27,28-d ih yd r oxyp e n t a cyclo[19.3.1.13,7.19,13.115,19]oct a -
cosa -1(24),3,5,7(28),9,11,13(27),15,18,21-d eca en e-25,26-d i-
on e (4): mp 178.2 °C (determined by TG-DTA); 1H NMR
(CD3OD-CDCl3) δ 1.21 (t, d ) 7.0 Hz,12H), 2.20 (s, 6H), 3.44
(q, J ) 7.0 Hz, 8H), 3.72 (s, 6H), 3.85 (s, 2H), 6.43-6.52 (m,
4H), 6.58-6.65 (m, 4H), 6.92 (dd, J ) 0.9, 5.1 Hz, 2H), 7.01
(dd, J ) 0.9, 7.1 Hz, 2H), 7.07 (s, 4H); FTIR (KBr) 1599; mass
spectrum m/ z 773 (M+ + 1). Anal. Calcd for C50H52N4O4: C,
77.69; H, 6.78; N, 7.25. Found: C, 77.38; H, 6.91; N, 6.88.
11,23-Bis((4′-(d iet h yla m in o)-2′-m et h ylp h en yl)im in o)-
26,28-d ih yd r oxyp e n t a cyclo[19.3.1.13,7.19,13.115,19]oct a -
cosa -1(24),3,5,7(28),9,12,15,17,19(26),21-d eca en e-25,27-d i-
1
on e (5): mp 161-167 °C (determined by TG-DTA); H NMR
(CD3OD-CDCl3) δ 1.16 (t, J ) 6.8 Hz, 12H), 2.23 (s, 6H), 3.39
(q, J ) 7.0 Hz, 8H), 3.70 (s, 8H), 6.52-6.64 (m, 8H), 6.88 (d, J
) 7.3 Hz, 4H), 7.15 (s, 4H); FTIR (KBr) 1596; mass spectrum
m/ z 776 (M+ + 4). Anal. Calcd for C50H52N4O4: C, 77.69; H,
6.78; N, 7.25. Found: C, 77.32; H, 6.87; N, 7.09.
5,11,17,23-Tetr akis((4′-(dieth ylam in o)-2′-m eth ylph en yl)-
i m i n o ) p e n t a c y c l o [ 1 9 . 3 . 1 . 1 3 . 7 . 1 9 . 1 3 . 1 1 5 . 1 9 ] o c t a -
cosa -1(24),3,6,9,12,15,18,21-oct a e n e -25,26,27,28-t e t r a -
1
on e (6): mp 157-160 °C; H NMR (DMSO-d6; 425 K) δ 1.16
(t, J ) 7.0 Hz, 24H), 2.08 (s, 12H), 3.37 (q, J ) 6.9 Hz, 16H),
3.49 (s, 8H), 6.52 (s, 8H), 6.62 (s, 4H), 7.03 (s, 8H); FTIR (KBr)
1600; mass spectrum m/ z 1121 (M+ + 1). Anal. Calcd for
C72H80N8O4: C, 77.11; H, 7.19; N, 9.99. Found: C, 77.06; H,
7.29; N, 9.82.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined on a
Mitamurariken micromelting point apparatus or a Mac Science
TG-DTA 2000 thermal analyzer and are uncorrected. Absorp-
tion spectra were measured using a J ASCO Ubest-30 spec-
trophotometer. NMR spectra were taken on General Elec-
tronics QE-300 (300 MHz) and Bruker AC200 (200 MHz) or
AM400 or ARX (400 MHz) spectrometers. IR spectra were
recorded by using a J ASCO FT/IR-5000 spectrophotometer,
and Perkin-Elmer System 2000. Mass spectra were run on a
Hitachi M-80A spectrometer and elemental analyses were
obtained using a Perkin-Elmer 240C C, H, N analyzer.
Ma ter ia ls. Unless specified otherwise, reagent-grade re-
actants and solvents were used as received from chemical
suppliers. Calix[4]arene 1 was synthesized by the method
described previously.12 Compound 9,10c 25,27-bis((ethoxycar-
bonyl)methoxy)-26,28-dihydroxypentacyclo[19.3.1.1.3,7.19,13.115,19]-
octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-do-
decaene, was prepared by the reaction of 1 with 2 equiv of
ethyl bromoacetate in the presence of K2CO3 in dry acetone
(37% yield): 1H NMR (CDCl3) δ 1.34 (t, J ) 7.2 Hz, 6H), 3.38
and 4.48 (d, J ) 13.2 Hz, 4H), 4.31 (q, J ) 7.2 Hz, 4H), 4.72
(s, 4H), 6.70 (t, J ) 7.5 Hz, 2H), 6.74 (t, J ) 7.6 Hz, 2H), 6.89
(d, J ) 7.4 Hz, 4H), 7.04 (d, J ) 7.4 Hz, 4H), 7.56 (s, 2H).
Con d en sin g Ca lix[4]a r en e 1 w ith 4-(Dieth yla m in o)-2-
m eth yla n ilin e Hyd r och lor id e (2). Typical procedure is as
follows (Table1, run 4): to an aqueous acetone solution of 1
(500 mg, 1.18 mmol), 2 (4.05g, 18.9 mmol), and NaOH (1.25 g,
29.6 mmol) at room temperature was added dropwise an
aqueous solution of K3[Fe(CN)6] (12.4 g, 32.7 mmol). The
resulting mixture was stirred for 10 min at room temperature.
It was then poured into water (100 mL). After the acetone
solvent was removed under reduced pressure, the crude
P r ep a r a t ion of 1,3-Bis(in d oa n ilin e)-Der ived 2,4-Bis-
((eth ylca r bon yl)m eth oxy)ca lix[4]a r en e 7. To an anhy-
drous dimethylformamide (DMF) solution (10 mL) of com-
pound 5 (50 mg, 0.065 mmol) in the presence of NaH (12.56
mg, 0.31 mmol) at room temperature was added an anhydrous
DMF solution (1 mL) of ethyl bromoacetate (0.05 mL, 0.41
mmol). The resulting mixture was stirred for 1 h at 80 °C. It
was then poured into ice water (100 mL). The solution was
made acidic (pH ) 5) by adding acetic acid and then was
extracted with CHCl3
(200 mL). The CHCl3 extract was taken
to dryness under reduced pressure. The residue was then
purified by column chromatography on silica gel (Wakogel
C-300) using CHCl3 as eluent to provide 38 mg of compound 7
(62% yield).
11,23-Bis((4′-(d iet h yla m in o)-2′-m et h ylp h en yl)im in o)-
2 6 ,2 8 -b i s ((e t h o x y c a r b o n y l )m e t h o x y )p e n t a c y c l o -
[19.3.1.13,7.19,13.115,19]oct a cosa -1(24),3,5,7(28),9,12,15,17,
19(26),21-d eca en e-25,27-d ion e (7): mp 110-112 °C; 1H NMR
(DMSO-d6; 373 K) δ 1.04-1.35 (m, 18H), 2.20 (s, 6H), 3.21-
3.45 (m, 12H), 3.73-3.93 (brd, 4H), 3.98-4.29 (brd, 4H), 4.47-
4.69 (brd, 4H), 6.47-6.82 (m, 12H), 7.10 (s, 2H), 7.19 (s, 2H);
FTIR (KBr) 1755, 1628; mass spectrum m/ z 945 (M+ +1).
Anal. Calcd for C58H64N4O8: C, 73.71; H, 6.83; N, 5.93.
Found: C, 73.07; H, 6.82; N, 5.81.
P r ep a r a t ion of 1,2-Bis(in d oa n ilin e)-Der ived 3,4-Bis-
((eth oxyca r bon yl)m eth oxy)ca lix[4]a r en e 8. To an anhy-
drous DMF solution (13 mL) of compound 5 (200 mg, 0.26
mmol) in the presence of NaH (64 mg, 1.6 mmol) at room
temperature was added an anhydrous DMF solution (3 mL)
of ethyl bromoacetate (0.18 mL, 1.63 mmol). The resulting