A New Family of Indoaniline-Derived Calixarenes: Synthesis and Optical Recognition Properties as a Chromogenic Receptor

Article abstract of DOI:10.1021/jo951907w

A new family of indoaniline-derived calix<4>arenes has been synthesized for the purpose of developing a new chromogenic receptor.A considering reaction of calix<4>arene (1) with 4-(diethylamino)-2-methylaniline hydrochloride (2) in the presence of an oxidizing agent under alkaline conditions affords mono- (3), 1,2-bis- (4), 1,3-bis- (5), and tetrakisindoaniline-derived (6) calix<4>arenes after careful column chromatography.Compound 3 is crystallized from a CHCl3-MeOH solution, and the crystal structure was determined by X-ray analysis.The crystal is monoclinic, space group P2₁/n, Z = 4, a = 19.507(6) Angstroem, b = 18.591(6) Angstroem, c = 8.524(2) Angstroem, β = 94.69(2) deg.The final R value for 2406 reflections of F₀ > 3?(F₀) is 0.085.A unique intramolecular hydrogen-bonding network involving the carbonyl oxygen of indoaniline for 3 implied that the quinone carbonyl group as an acceptor of the chromophore can easily be subjected to an electrostatic interaction in the lower rim.Indeed, 1,3-bis(indoaniline)-derived 2,4-bis((ethoxycarbonyl)methoxy)calix<4>arene 7, prepared by the reaction of 5 with ethyl bromoacetate in the presence of NaH, is capable of undergoing an efficient ion-dipole interaction between the binding cation and the two quinone carbonyl groups of the chromophores, so that a selective Ca(2+)-induced pronounced color change (wavelength change > 100 nm) occurs with an association constant on the order of 10⁶ in 99 percent EtOH, making 7 of potential use as an optical sensor for Ca(2+) detection.The IR and NMR studies have indicated that potential use as an optical sensor for Ca(2+) detection.The IR and NMR studies have indicated that Ca(2+) is encapsulated in the cavity made by the distally located OCH2CO2 groups on the lower rim of the cone-shaped calix<4>arene segment.Interestingly, however, the shape of the cavity in which Ca(2+) has been encapsulated does not have a C₂ axis of symmetry, as inferred from the 1H-1H COSY experiment.On the other hand, 1,2-bis(indoaniline)-derived analogue 8 shows no response with metal ions, which can be interpreted to mean the absecne of a cavity for encapsulation on the lower rim.

Full text of DOI:10.1021/jo951907w

3758
J . Org. Chem. 1996, 61, 3758-3765
A New F a m ily of In d oa n ilin e-Der ived Ca lix[4]a r en es: Syn th esis
a n d Op tica l Recogn ition P r op er ties a s a Ch r om ogen ic Recep tor 1
Yuji Kubo,*,† Sumio Tokita,† Yuko Kojima,‡ Yasuko T. Osano,‡ and Takao Matsuzaki‡
Department of Applied Chemistry, Faculty of Engineering, Saitama University, 255 Shimo-ohkubo,
Urawa, Saitama 338, J apan, and Mitsubishi Kagaku Corporation, Yokohama Research Center, 1000
Kamoshida, Aoba-ku, Yokohama 227, J apan
Received October 26, 1995X
A new family of indoaniline-derived calix[4]arenes has been synthesized for the purpose of developing
a new chromogenic receptor. A condensing reaction of calix[4]arene (1) with 4-(diethylamino)-2-
methylaniline hydrochloride (2) in the presence of an oxidizing agent under alkaline conditions
affords mono- (3), 1,2-bis- (4), 1,3-bis- (5), and tetrakisindoaniline-derived (6) calix[4]arenes after
careful column chromatography. Compound 3 is crystallized from a CHCl3-MeOH solution, and
the crystal structure was determined by X-ray analysis. The crystal is monoclinic, space group
P21/n , Z ) 4, a ) 19.507(6) Å, b ) 18.591(6) Å, c ) 8.524(2) Å, â ) 94.69(2)°. The final R value for
2406 reflections of Fo > 3σ(Fo) is 0.085. A unique intramolecular hydrogen-bonding network
involving the carbonyl oxygen of indoaniline for 3 implied that the quinone carbonyl group as an
acceptor of the chromophore can easily be subjected to an electrostatic interaction in the lower
rim. Indeed, 1,3-bis(indoaniline)-derived 2,4-bis((ethoxycarbonyl)methoxy)calix[4]arene 7, prepared
by the reaction of 5 with ethyl bromoacetate in the presence of NaH, is capable of undergoing an
efficient ion-dipole interaction between the binding cation and the two quinone carbonyl groups
of the chromophores, so that a selective Ca2+-induced pronounced color change (wavelength change
> 100 nm) occurs with an association constant on the order of 106 in 99% EtOH, making 7 of
potential use as an optical sensor for Ca2+ detection. The IR and NMR studies have indicated that
Ca2+ is encapsulated in the cavity made by the distally located OCH2CO2 groups on the lower rim
of the cone-shaped calix[4]arene segment. Interestingly, however, the shape of the cavity in which
Ca2+ has been encapsulated does not have a C2 axis of symmetry, as inferred from the 1H-1H
COSY experiment. On the other hand, 1,2-bis(indoaniline)-derived analogue 8 shows no response
with metal ions, which can be interpreted to mean the absence of a cavity for encapsulation on the
lower rim.
In tr od u ction
noteworthy for the development of optical fiber sensors
to measure the concentration of desired species in clinical
analysis.4 Human blood plasma usually contains Na+,
K+, Mg2+, and Ca2+ ions.5 While chromogenic receptors
for Na+ and K+ are well-known,6 studies on Ca2+ for such
purposes are limited.2a,7
Our interest in the development of advanced functional
molecules leads us to incorporate a biological function
such as receptor, transporter, enzyme, and so on into
materials for electrooptical applications because the
cooperation of these functions produces new types of
molecular devices. In this context, recently, we have been
intrigued by the synthesis of chromogenic receptors that
are defined dye molecules capable of binding a guest in
the antenna segment. The binding of the guest induces
a change in the physical properties of the chromophore
as an optical sensory site. These artificial receptors have
attracted considerable attention as efficient spectro-
photometric analytical reagents for the detection of
particular species,2 as well as for fundamental aspects
of molecular devices possessing recognition and signal
sensing.3 Particularly, in the former cases, the inherently
sensitive nature of optical signaling makes it possible to
perform the selective determination of biologically im-
portant species. Hence such molecules are extremely
(4) Borman, S. Anal. Chem. 1987, 59, 1161A.
(5) Lehninger, A. L. In Principles of Biochemistry; Worth Publisher,
Inc.: New York, 1982; p 56.
(6) (a) Cram, D. J .; Chapoteau, E.; Czech, B. P.; Gebauer, C. R.;
Helgeson, R. C.; Kumer, A. In Inclusion Phenomena and Molecular
Recognition; Atwood, J ., Ed.; Plenum Press: New York, 1990; p 217
and references cited therein. (b) Al-Amer, S. M. S.; Ashworth, D. C.;
Narayanaswamy, R.; Moss, R. E. Talanta 1989, 36, 645. (c) Inoue, M.;
Ueno, M.; Kitao, T.; Tsuchiya, K. J . Am. Chem. Soc. 1990, 112, 8977.
(d) Reichardt, C.; Asharin-Fard, S. Angew. Chem., Int. Ed. Engl. 1991,
30, 558. (e) Kubo, Y.; Hamaguchi, S.; Kotani, K.; Yoshida, K. Tetra-
hedron Lett. 1991, 32, 7419. (f) King, A. M.; Moore, C. P.; Sandanayaka,
K. R. A. S.; Sutherland, I. O. J . Chem. Soc., Chem. Commun. 1992,
582. (g) Danks, I. P.; Sutherland, I. O. J . Incl. Phenom. Mol. Recognit.
Chem. 1992, 12, 223. (h) McCarrick, M.; Wu, B.; Harris, S. J .; Diamond,
D.; Barrett, G.; McKervey, M. A. J . Chem. Soc., Chem. Commun. 1992,
1287. (i) Sholl, A. F.; Sutherland, I. O. J . Chem. Soc., Chem. Commun.
1992, 1716. (j) Chapoteau, E.; Czech, B. P.; Kumer, A.; Zazulak, W. J .
Incl. Phenom. Mol. Recognit. Chem. 1993, 16, 367. (k) Sadanayake, K.
R. A. S.; Sutherland, I. O. Tetrahedron Lett. 1993, 34, 3165. (l) Dolman,
M.; Sutherland, I. O. J . Chem. Soc., Chem. Commun. 1993, 1793. (m)
Yamamoto, H.; Ueda, K.; Sandanayake, K. R. A. S.; Shinkai, S. Chem.
Lett. 1995, 497.
(7) Ashworth, D. C.; Huang, H. P.; Narayanaswamy, R. Anal. Chim.
Acta 1988, 213, 251. Bartsch, R. A.; Chapoteau, E.; Czech, B. P.;
Krzykawski, J .; Kumar, A.; Robison, T. W. J . Org. Chem. 1994, 59,
616 and references cited therein. Mason, A.; Sutherland, I. O. J . Chem.
Soc., Chem. Commun. 1994, 1131. Some fluorescent probes for calcium
have been synthesized: Poenie, M.; Alderton, J .; Tsien, R. Y.; Stein-
hardt, R. A. Nature 1985, 315, 147. Grynkiewicz, G.; Poenie, M.; Tsien,
R. Y. J . Biol. Chem. 1985, 260, 3446. Tsien, R. Y. Biochemistry 1980,
19, 2396. Smith, G. A.; Metcalfe, J . C.; Clarke, S. D. J . Chem. Soc.,
Perkin Trans. 2 1993, 1195.
† Saitama University.
‡ Mitsubishi Kagaku Corp.
X Abstract published in Advance ACS Abstracts, May 1, 1996.
(1) Preliminary account: Kubo, Y., Hamaguchi, S.; Niimi, A.;
Yoshida, K.; Tokita, S. J . Chem. Soc., Chem. Commun. 1993, 305.
(2) For comprehensive reviews, see; (a) Takagi, M.; Ueno. K. Top.
Curr. Chem., 1984, 121, 39. (b) Lo¨hr, H.-G.; Vo¨gtle, F. Acc. Chem. Res.
1985, 18, 65.
(3) Lehn, J .-M. Angew. Chem., Int. Ed. Engl. 1988, 27, 89. Lehn,
J .-M. In Frontiers in Supramolecular Organic Chemistry and Photo-
chemistry; Schneider, H. J ., Du¨rr, H., Eds.; VCH: Weinheim, 1991; p
1.
S0022-3263(95)01907-4 CCC: $12.00 © 1996 American Chemical Society

A New Family of Indoaniline-Derived Calix[4]arenes
J . Org. Chem., Vol. 61, No. 11, 1996 3759
Calixarenes8 are cyclic oligomers of varying ring size
derived from para-substituted phenols and formaldehyde.
The availability for chemical modification at the phenolic
OH groups (lower rim) or at the aromatic nuclei (upper
rim) has allowed the calixarenes to function as hosts for
ions or small molecules.8 Therefore, if one could intro-
duce an appropriate optical sensory group into a calix-
arene bearing a preorganized guest-binding site, an
encapsulated species would cause a physical change in
the opto-functional site which can be monitored by
spectroscopy. As such, there has been emphasis on the
synthesis of “chromogenic” 6efhl,9 and “fluorogenic” 10 calix-
[4]arenes with the aim of developing new types of optical
receptors. An indoaniline chromophore system, prepared
by condensing phenol derivatives with (N,N-dialkyl-
amino)anilines, may be important in this area because
its optical properties can be perturbed significantly by
chemical stimuli. Indeed, we found that the quinone
carbonyl group of indoaniline-type ligands interacts with
divalent metal ions to cause a pronounced color change.11
Thus, the combined use of the chromophore constrained
within a calixarene receptor framework would be of great
interest in the design of chromogenic receptors; the
inclusion of a positively charged species in the cavity
would then, it was thought, cause a significant electro-
static perturbation of the chromophore. This paper
describes the synthesis of several new types of indo-
aniline-derived calix[4]arene derivatives. Among them,
compound 7, containing two indoaniline chromophores
designed to combine the specific complexation of the two
ethyl acetate groups attached in a 1,3-fashion to oxygens
on the lower rim, shows a large bathochromic shift
Sch em e 1
arenes (3, 4, 5, and 6) after chromatography (Scheme 1).
The structures were identified by observed analytical
data (see Experimental Section). In this case, bis-
(indoaniline)-derived analogues 4 and 5 are regioisomers.
The assignments of the structure were, therefore, care-
fully conducted using NMR spectroscopy. In CDCl3
solution, the compound exists as a mixture of conformers
that interconvert slowly on the NMR time scale at room
temperature. However, addition of CD3OD into the
solution results in the reduction of several intramolecular
hydrogen bonds in the lower rim of the calix[4]arene ring,
the equilibrium becomes fast on the NMR time scale, and
averaged spectra have been obtained as shown in Figure
1. One can find that the signals from the ArCH2Ar are
characteristic of the structure since a quinone group
adjacent to the methylene is known to induce an upfield
shift of the methylene resonance.13 Actually, compound
4, possessing proximally positioned indoaniline chro-
induced by recognition of Ca2+
.
Resu lts a n d Discu ssion
Syn th esis a n d Str u ctu r e. The incorporation of an
indoaniline chromophore with a calixarene was syntheti-
cally easy: condensing calix[4]arene 112 with 4-(diethyl-
amino)-2-methylaniline hydrochloride (2) under alkaline
conditions in the presence of K3[Fe(CN)6] as an oxidizing
agent afforded four types of indoaniline-derived calix[4]-
(8) (a) Gutsche, C. D. In Calixarene, Monographs in Supramolecular
Chemistry; Stoddart, J . F., Ed.; The Royal Society of Chemistry,
Cambridge: 1989. (b) In Calixarenes, A. Versatile Class of Macrocyclic
Compounds; Vicens, J ., Bo¨hmer, V., Eds.; Kluwer: Dordrecht, 1991.
For recent reviews, see: (c) Shinkai, S. In Advances in Suparmolecular
Chemistry, Vol. 3; Gokel, G. W., Ed.; J AI Press Inc.: Greenwich, 1993;
p 97. (d) Bo¨hmer, V.; O’Sullivan, P. Trends Polm. Sci. (Cambridge,
U.K.) 1993, 1, 267. (e) Shinkai, S. Tetrahedron 1993, 49, 8933. (f)
Takeshita, M.; Shinkai, S. Bull. Chem. Soc. J pn. 1995, 68, 1088. (g)
Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713.
(9) (a) Shinkai, S.; Araki, K.; Shibata, J .; Tsugawa, D.; Manabe, O.
Chem. Lett. 1989, 931. (b) Nomura, E.; Taniguchi, H.; Tamura, S.
Chem. Lett. 1989, 1125. (c) Shimizu, H.; Iwamoto, K.; Fujimoto, K.;
Shinkai, S. Chem. Lett. 1991, 2147. (d) McCarrick, M.; Harris, S. J .;
Diamond, D. J . Mater. Chem. 1994, 4, 217. (e) Chawla, H. M.; Srinivas,
K. Tetrahedron Lett. 1994, 35, 2925. (f) Kubo, Y.; Maeda, S.; Nakamura,
M.; Tokita, S. J . Chem. Soc., Chem. Commun. 1994, 1725. (g) Chawla,
H. M.; Srinivas, K. J . Chem. Soc., Chem. Commun. 1994, 2593. (h)
Kubo, Y.; Maruyama, S.; Ohhara, N.; Nakamura, M.; Tokita, S. J .
Chem. Soc., Chem. Commun. 1995, 1727. (i) Gordon, J . L. M.; Bo¨hmer,
V.; Vogt, W. Tetrahedron Lett. 1995, 36, 2445.
(10) (a) J in, T.; Ichikawa, K.; Koyama, T. J . Chem. Soc., Chem.
Commun. 1992, 499. (b) Aoki, I.; Sakai, T.; Tsutsui, S.; Shinkai, S.
Tetrahedron Lett. 1992, 33, 89. (c) Aoki, I.; Sakai, T.; Shinkai, S. J .
Chem. Soc., Chem. Commun. 1992, 730. (d) Iwamoto, K.; Araki, K.;
Fujishima, H.; Shinkai, S. J . Chem. Soc., Perkin Trans. 1 1992, 1885.
(e) Pe´rez-J ime´nez, C.; Harris, S. J .; Diamond, D. J . Mater. Chem. 1994,
4, 145. (f) Takeshita, M.; Shinkai, S. Chem. Lett. 1994, 125. (g)
Takeshita, M.; Shinkai, S. Chem. Lett. 1994, 1349. (h) Matsumoto,
H.; Shinkai, S. Tetrahedron Lett. 1996, 37, 77.
1
mophores, displays in the H NMR two singlets in a 3:1
ratio for the methylene protons (δ 3.72 and 3.85). These
results indicate that one of bridging methylenes in the
calix[4]arene skeleton binds to phenol residues on both
sides (Figure 1; A). On the other hand, the ArCH2Ar
bridging methylene resonance of compound 5 is a singlet
at 3.70, in agreement with a 1,3-bis-substituted (distal)
compound.
Table 1 summarized the results of the condensing
reaction of 1 with 2. It seemed likely that the number
of indoaniline chromophores incorporated with the calix-
[4]arene increased as the [2]:[1] molar ratio and reaction
time increased. In the case of run 2, the compounds 4
and 5 were obtained in 25% and 35% yields, respectively.
To obtain a better understanding of the conformation
for indoaniline-derived calix[4]arene, it is important to
elucidate the X-ray structure. After several trials, the
crystal structure for 3 has been determined. The ORTEP
(13) Morita, Y.; Agawa, T.; Kai, Y.; Kasai, N.; Nomura, I.; Taniguchi,
H. Chem. Lett. 1989, 1349.
(11) Kubo, Y.; Sasaki, K.; Kataoka, H.; Yoshida, K. J . Chem. Soc.,
Perkin Trans. 1 1989, 1469.
(12) Gutsche, C. D.; Lin, L. Tetrahedron 1986, 42, 1633.
(14) Brown, G. H.; Figueras, J .; Gledhill, R. J .; Kibler, C. J .;
McCrossen, F. C.; Parmerter, S. M.; Vittum, P. W.; Weissberger, A. J .
Am. Chem. Soc. 1957, 79, 2919.

3760 J . Org. Chem., Vol. 61, No. 11, 1996
Kubo et al.
F igu r e 2. X-ray crystallographic structure of 3.
Ta ble 2. In tr a m olecu la r Hyd r ogen Bon d in g for th e
X-r a y Str u ctu r e of 3
Oa-Ha
(Å)
Ha-Ob
(Å)
Oa- -Ob
(Å)
Oa-Ha- -Ob
(deg)
Oa-Ha- -Ob
O15-H15- -O7
1.0(1)
1.0(1)
1.0(1)
1.7(1)
1.8(1)
1.7(1)
2.60(1)
2.72(1)
2.65(1)
154(10)
158(9)
153(10)
O
O
23-H23- -O15
31-H31- -O7
Actually, dual intramolecular hydrogen bondings be-
tween the carbonyl oxygen (O7) and H15 and H31 were
observed with the interatomic distances of C15- - -O7 and
O31- - -O7 being 2.60(1) and 2.65(1) Å, respectively (Table
2). These results implied that the quinone carbonyl
group as an acceptor of the indoaniline chromophore can
easily be subjected to an electrostatic interaction that
takes place on the lower rim of calixarene and that
functionalization of the lower rim would be profitable to
produce a new type of chromogenic receptor. Looking at
the chromophore, the aniline ring is tilted out of ring A
by 31.4 (3)° because of steric repulsion between the
hydrogens attached to C(2) and C(35). With the aim of
developing the desired receptor, an anchoring functional
group oriented in such a way that it delineates a suitable
binding site is required; we decided to append ethyl
acetate groups on the lower rim of the calix[4]arene
platform for compounds 4 and 5 that possess two chro-
mophores, depending on design as effective optical sens-
ing sites, in the molecule. As shown in Scheme 2, the
ethoxycarbonylmethylations of 4 and 5 were accom-
plished with ethyl bromoacetate in the presence of NaH
to give the corresponding desired analogues 8 and 7 in
54% and 62% yields, respectively. An alternative route
to 7 involves the reaction of 1,3-bis((ethoxycarbonyl)-
methoxy)calix[4]arene (9)10c (Chart 1) with 2 in an
MeOH-acetone solution. In spite of several trials, 7
F igu r e 1. 1H NMR spectra of 4 and 5 in CD3OD-CDCl3 at
300 MHz; * is signal of solvent.
Ta ble 1. Syn th esis of In d oa n ilin e-Der ived
Ca lix[4]a r en esa
molar ratio
[2]/[1]
[ox]b/[1]
yield, %
run
RT,c min
3
4
5
6
1
2
3
4
16
16
8
32
32
120
10
240
50
2
-
11.5
25
3
8
35
1
trace
trace
37.5
a
The procedure is similar to that described in ref 14.
K3[Fe(CN)6]. c Reaction time.
b
diagram is illustrated in Figure 2 with selected labeling.
Compound 3 in a solid state exhibits the calix in a cone
conformation; the dihedral angles between the aromatic
units of the calix[4]arene skeleton through the methylene
carbons are 112.4(8), 113. 1(8), 114.2 (7), and 110.1(7)°,
respectively. These are slightly smaller than the corre-
sponding values (123-126°) observed for the p-tert-butyl-
15
and the p-isopropylcalix[4]arene,16 probably attribut-
able to a unique intramolecular hydrogen-bonding network
involving the carbonyl oxygen of indoaniline for 3.
(15) Andreetti, G. D.; Ungaro, R.; Pochini, A. J . Chem. Soc., Chem.
Commun. 1979, 1005.
(16) Perrin, M.; Oehler, D., in ref 8b.

A New Family of Indoaniline-Derived Calix[4]arenes
J . Org. Chem., Vol. 61, No. 11, 1996 3761
Sch em e 2
Ch a r t 1
Ta ble 3. Absor p tion Sp ectr a of Ch r om ogen ic
Com p ou n d s in n -Bu tyl Aceta te
compd
λ
max/nm (ꢀmax, dm3 mol-1 cm-1
)
3
4
5
6
7
661 (45 000)
643 (33 000)
634 (39 000)
617 (58 000)
583 (35 000)
605 (38 000)
589 (18 000)
598 (16 000)
646 (18 000)
8
F igu r e 3. Spectral changes upon addition of Ca(SCN)2‚4H2O
10
1118
1218
to a solution of 7 in 99% EtOH; [7] ) 1.5 × 10-5 mol dm-3
.
absorb visible light at 634 nm (ꢀmax 39 000 dm3 mol-1
cm-1) and 583 nm (ꢀmax 35 000 dm3 mol-1 cm-1) in n-butyl
acetate; the disappearance of an intramolecular hydrogen-
bonding interaction between the carbonyl group of the
chromophore and the adjacent phenolic-OH group by
introducing the ethyl acetate group causes a hypsochro-
mic shift of 51 nm,17 in agreement with the difference in
wavelengths (48 nm) between the related indoanilines
11 and 12 (Chart 2).18 These findings, in turn, have led
us to consider that a metal ion, which is encapsulated in
the cavity constructed with OCH2CO2 groups for 7, could
cause a significant ion-dipole interaction with two
quinone carbonyl groups of the chromophores and then
would induce some intense spectral change in the ab-
sorption. A substantial difference, in fact, appears when
we examine the effect of the optical response of the
ligands to addition of Na+, K+, Mg2+, and Ca2+ ions. As
shown in Figure 3, compound 7 is blue and has a λmax
value of 609 nm (ꢀmax 35 000 dm3 mol-1 cm-1) in 99%
EtOH; stepwise addition of Ca(SCN)2‚4H2O to compound
7 in the solution causes a large bathochromic shift with
an increase in absorption intensity with isosbestic points
at 460 and 630 nm, respectively. At a [Ca2+] to [7] ratio
of 5:1, a new absorption band in the near-IR region at
724 nm was observed while the absorption band at 609
nm disappeared completely. The understanding of the
binding profile came from a continuous variation method19
using mixtures of 7 and Ca2+ in 99% EtOH under
conditions of invariant total concentration. This ap-
Ch a r t 2
cannot be detected by the reaction using 9, probably due
to the fact that a hydrolysis reaction of the ethyl acetate
segment takes place during the condensing reaction.
Sp ect r a l Ch a r a ct er ist ics of t h e Ch r om ogen ic
Com p ou n d s. Wavelength maxima (λmax) and the mo-
lecular extinction coefficients of the chromogenic calix-
[4]arenes as well as related compounds are summarized
in Table 3. Mono(indoaniline)-derived 3 (λmax ) 661 nm)
shows the largest bathochromic shift (72 nm) among the
related compounds, compared to that of control 10 (Chart
2), which indicates that the indoaniline chromophore
appears to be influenced by dual intramolecular hydrogen
bonding between the carbonyl group of the chromophore
and adjacent phenolic-OH groups. Consistent with this
result is the X-ray crystal structure of 3, which shows
the calix in a cone conformation (vide supra). Compound
6, the tetrakis(indoaniline)-derived calix[4]arene, absorbs
visible light at 617 nm, the ꢀmax of which is 58 000 dm3
mol-1 cm-1, 3.2 times that of 10 because multiple chro-
mophores exist in the structure. Regarding the bis-
(indoaniline)-derived compounds, compounds 5 and 7
(17) Similarly, the λmax values of 8 is shorter by 38 nm than that of
4.
(18) Lurie, A. P.; Brown, G. H.; Thirtle, J . R.; Weissberger, A. J .
Am. Chem. Soc. 1961, 83, 5015.
(19) Ueno, K. In Numon Chelate Kagaku; Nankodo: Tokyo, 1969;
p 56.

3762 J . Org. Chem., Vol. 61, No. 11, 1996
Kubo et al.
Ta ble 4. IR Sp ectr a l Da ta of CdO for th e Ca 2+-7
Com p lex
υ, cm-1
compd
CdO (ester)
CdO (quinone)
7
1755
1721
1628
1593
Ca2+-7
vs proximal-ethyl acetated derivatives provoke a drastic
stereochemical dependence of cation complexation ability.
Furthermore, the cyclic indoaniline tetramer 6 shows an
unfavorable complexation property with Ca2+, also indi-
cating that disposition of ethyl acetate groups is signifi-
cantly important. In recent years, a calixarenequinone
derivative possessing a cavity shape similar to that of 7
has been reported with the aim of recognition of guest
cations.20
Selective Com p lexa tion Beh a vior for 7. IR spec-
troscopy was used to obtain insight into the coordination
structure of the Ca2+-7 complex. The frequency of both
CdO (ester) and CdO (quinone) absorptions for the
complexes are lower by 34-35 cm-1 than those of the free
ligand (Table 4). From these results, compound 7 could
form an encapsulated complex with Ca2+ in the cavity
made by the distally located OCH2CO2 groups on the
lower rim. Hence, a rather specific Ca2+-induced batho-
chromic shift could be explained on the basis of a well-
tailored electrostatic interaction between the encapsu-
lated cations and quinone carbonyl groups of the
indoaniline chromophore. The excited state of the chro-
mophore might be more stabilized by the cation than the
ground state. This consideration is supported by the fact
that compound 10 shows no color change with alkali and
alkaline earth metal ions in a control experiment.
Some NMR studies were carried out in an effort to
understand further details of the cation-receptor inter-
F igu r e 4. Continuous variation plot of the Ca2+-7 complex
in 99% EtOH; [7] + [Ca2+] ) 2.0 × 10-5 mol dm-3; o.d. 722
nm.
1
actions. Figure 6 shows H NMR spectra of ligand 7 and
the Ca2+-complex after solid [Ca(SCN)2‚4H2O]-liquid
[CDCl3] two-phase solvent extraction. At 24 °C in CDCl3,
ligand 7 exhibited a relatively broadened spectral pat-
tern, which indicated that conformational interconversion
is somewhat slow on the NMR time scale. However, upon
interaction with Ca2+, the spectra changed from the broad
signal to split patterns in CDCl3 with a downfield shift
of 0.24 and 0.41 ppm, respectively, for the resonances of
CO2CH2CH3 (Figure 6b). This result can be explained
on the basis of a restriction of the interconversion by
complexation with Ca2+, the process of which involves
an arrangement for the cavity in order to accommodate
the Ca2+ appropriately and the encapsulated cation- - -
carbonyl oxygens (host) ion-dipole interaction. In a
further attempt to assign the intricate signals of the
complex using a 1H-1H COSY experiment (see Figure
7), the bridging methylene resonances could be assigned
as four pairs of doublets in 1:1:1:1 integral intensity
proportions, as substantiated by appropriate cross-peaks
in the spectra. The chemical shifts for Hexo are δ 3.07,
3.10, 3.17, and 3.20 ppm, whereas those for Hendo are δ
4.19, 4.33, 4.06, and 4.19 ppm. Such findings indicate
that the complex has been frozen out in a cone conforma-
tion according to the fact that ∆δ values between Hexo
and Hendo are ca. 1 ppm.8a Another interesting feature
is that methylene resonances of the ethyl acetate groups
displayed singlet (4.06 ppm) and AB patterns [4.53, 4.81
ppm (J ) 15.6 Hz)], each integrating for two protons and
undergoing an upfield shift of 1.08, 0.61, and 0.33 ppm,
F igu r e 5. Influence of added NaSCN, KSCN, Mg(ClO4)2, and
Ca(SCN)2‚4H2O on the absorption spectra of 7 (9) and 8 (b).
proach, as illustrated in Figure 4, reveals that the
relative 7-Ca2+ complex concentration approaches a
maximum when the molar fraction of 7 {[7]/([7] +
[Ca2+])} is approximately 0.5, as is expected for the
formation of a 1:1 complex between 7 and Ca2+
.
We then tested compound 7 to see if it acted as a
chromogenic receptor. Figure 5 shows spectral responses
(∆λ ) λ(complex) - λ(ligand)) in the presence (102 equiv)
or absence of metal salts. A large bathochromic shift of
110 nm was observed in the presence of Ca2+
. In
contrast, addition of NaSCN, KSCN, or Mg(ClO4)2 caused
only minor changes ranging from 12 to 40 nm in the
absorption spectra, suggesting that compound 7 exhibited
a significant selectivity for Ca2+. Alternatively, 1,2-bis-
substituted analogue 8 was quite inefficient in the
presence of those metal ions (even in addition of Ca2+
)
as shown in Figure 5. The examination of CPK space-
filling molecular models implies that compound 8 retains
no cavity to encapsulate metal ions on the lower rim of
the calix[4]arene segments. Thus, the lack of cation
response of 8 is considered to be due to the unfavorable
steric complementality between 8 and the cations. The
spectroscopic study, in this way, reveals a significant
difference between 7 and 8; it is intriguing that distal-
(20) Beer, P. D., Chen, Z.; Gale, P. A. Tetrahedron 1994, 50, 931.

A New Family of Indoaniline-Derived Calix[4]arenes
J . Org. Chem., Vol. 61, No. 11, 1996 3763
Ch a r t 3
Ta ble 5. Associa tion Con sta n ts (Ka ) a n d Bin d in g F r ee
En er gies (-∆G°) in 99% EtOH a t 25 °C
b
K, dm3 mol-1 [-∆G°, kcal mol-1
]
host
Na+
K+
Mg2+
Ca2+
7
3.7 × 104
2.5 × 105 d
3.2 × 105 c
8.9 × 103 d
100
[2.73]
< 100d
7.6 × 106 c
8.9 × 106 d
[6.23]
[7.51]
[9.39]
13
Determined from a Benesi-Hildebrand plot.22 1 cal ) 4.184
a
b
J . c Determined by the Rose-Drago method.23 In water.
d
Ch a r t 4
effect. Hence, the most upfield-shifted methylene protons
(4.06 ppm; singlet) might be held in a magnetically
equivalent “exo position” to the cavity constructed by
ether and ester oxygens; namely, if one assumes that the
orientation of the OCH2CO2Et side chain relative to its
benzene ring is described by the CaCb-ObCc torsion angle
(φ) for a plane perpendicular to the ring (see Chart 3),
the value would be 0°. Whereas the φ of the other side
chain, in which the methylene resonance appears at 4.53
and 4.81 ppm (AB pattern), might be an acute angle.
Consequently, the methylene bridge of the calix[4]arene
segment is considered to result in a split pattern upon
complexation. This finding is quite new because a
diester-calix[4]arene-diquinone20 and a tetraester-
derived calix[4]arene derivative21 usually exhibit two
pairs of doublets for the methylene bridge and one singlet
for OCH2COR upon complexation with cations. Pres-
ently, we are attempting to obtain an X-ray structure of
the complex to clarify such a result. The association
constants and binding free energies (-∆G°) are sum-
marized in Table 5. Compound 7 showed peak selectivity
for Ca2+ with a ∆G° value of -9.39 kcal mol-1, compa-
rable to that of the cryptand 1324 (Chart 4). It is
noteworthy that high Ca2+ selectivity over Na+ (∆∆G° )
-3.16 kcal mol-1) is obtained, in spite of their similar
ionic radii. This result can be interpreted in terms of
ion-dipole interaction; because Ca2+ has a higher charge
density than Na+, it should interact more strongly with
polar donor groups.25 As a competitive experiment,
treatment of compound 7 in 99% EtOH with a mixture
F igu r e 6. 1H NMR spectra (400 MHz, CDCl3, 24 °C) of 7 (a)
and Ca2+-7 complex (b).
F igu r e 7. 1H-1H NMR spectrum of the Ca2+-7 complex in
CDCl3 at 400 MHz.
respectively, in comparison with that of free ligand 7
(Figure 6). Taken together, these results suggest that
the shape of the cavity in which Ca2+ has been encap-
sulated does not have a C2 axis of symmetry. The upfield
shift-experienced OCH2CO2 protons of the side chain can
be explained by assuming that Ca2+-induced conforma-
tional change brings the methylene protons above the
aromatic rings where they experience a ring current
(21) Arudini, A.; Pochini, A; Reverberi, S; Ungaro, R. Tetrahedron
1986, 42, 2089.
(22) Benesi, H. A.; Hidebrand, J . H. J . Am. Chem. Soc. 1949, 71,
2703.
(23) Rose, N. J .; Drago, R. S. J . Am. Chem. Soc. 1959, 81, 6138.
(24) Lehn, J .-M.; Sauvage, J .-P. Chem. Commun. 1971, 440.
(25) Gatto, V. J .; Gokel, G. W. J . Am. Chem. Soc. 1984, 106, 8240.

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

A New Family of Indoaniline-Derived Calix[4]arenes
J . Org. Chem., Vol. 61, No. 11, 1996 3765
Ta ble 6. Exp er im en ta l Da ta for X-r a y Diffr a ction
Stu d ies of 3
mixture was stirred at ca. 6.8 h at 80 °C; during stirring an
anhydrous DMF solution (5 mL) containing NaH (25 mg, 0.63
mmol) and ethyl bromoacetate (0.1 mL, 0.91 mmol) was also
added as a second portion. After the disappearance of starting
material, the resulting solution was poured into ice water (100
mL). The solution was made acidic by adding acetic acid (pH
) 5) and then was extracted with CHCl3 (150 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 a CHCl3-C6H6 mixture (1:4 (v/v))
as eluent. In this way, 133 mg of 8 was obtained (54% yield).
17,23-Bis((4′-(d iet h ya m in o)-2′-m et h ylp h en yl)im in o)-
2 7 ,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 ,1 3 .11 5 ,1 9 ]o c t a c o s a -1(24),3,5,7(28),9,11,
13(27),15,18,21-d eca en e-25,26-d ion e (8): mp 128-130 °C;
1H NMR (DMSO-d6; 373 K) δ 1.06-1.26 (m, 18H), 2.21 (s, 6H),
3.16-3.35 (m, 4H), 3.35-3.49(m, 12H), 4.00-4.24 (brd, 4H),
4.29-4.53 (brd, 4H), 6.33-6.89 (brd, 12H), 6.89-7.09 (brd, 4H);
FTIR (KBr) 1761, 1622; mass spectrum m/ z 945 (M+ + 1).
Anal. Calcd for C58H64N4O8: C, 73.71; H, 6.83; N, 5.93.
Found: C, 72.75; H, 6.82; N, 5.39.
P r ep a r a tion of 10. To an aqueous EtOH solution (ca. 40
mL) of 2,6-dimethylphenol (1g, 8.19 mmol), NaOH (327 mg,
8.19 mmol), and 4-(diethylamino)-2-methylaniline hydro-
chloride (3.52 g, 16.4 mmol) was added dropwise an aqueous
solution of K3[Fe(CN)6] (10.78 g, 32.7 mmol). The resulting
mixture was stirred for 15 min at room temperature. It was
then poured into water and extracted with CHCl3. 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 an eluent and recrystal-
lized from MeOH to produce 1.34 g of 10 (55% yield).
formula
cryst syst
space group
C39H38N2O4
monoclinic
P21/n
cell parameters at 296 K
a, Å
19.507(6)
b, Å
18.591(6)
c, Å
8.524(2)
â, deg
94.69(2)
3081(1)
V
Z
4
dx, g cm-3
1.281
F(000)
1264
mol wt
594
diffractometer
ENRAF-Nonius CAD 4
scan mode
ω-0.67θ
maximum of sin θ/λ (Å-1
)
0.611
radiation
h min and max
Cu KR (λ ) 1.5418 Å), 40 kV, 80 mA
-24, 24
0, 23
k
l
-10,0
∆Fmax and ∆Fmin
(∆/σ)max
0.26, -0.31
0.18
0.085
R
1σ(F0) were considered as observed and used for the structure
determination. Lorenz and polarization corrections were
applied. The structure was solved by the direct method26 and
refined by full-matrix least-squares technique.27 The function
∑(Fo - Fc)2 was minimized. Non-hydrogen atoms were refined
anisotropically. Hydrogen atoms could be located on a differ-
ence Fourier map, but some of their positions were recalculated
geometrically. All H-atoms were included in the refinement
procedure with isotropic thermal parameters. The maximum
and minimum residual electron densities (F, e/Å3) on the final
difference Fourier map were 0.26 and -0.31, respectively.28
4-((4-(Dieth yla m in o)-o-tolyl)im in o)-2,6-d im eth ylcyclo-
1
h exa -2,5-d ien on e (10): mp 128-130 °C; H NMR (CDCl3) δ
1.21 (t, J ) 7.1 Hz, 6H), 2.02 (d, J ) 1.3 Hz, 3H), 2.09 (d, J )
1.5 Hz, 3H), 2.29 (s, 3H), 3.40 (q, J ) 7.1 Hz, 4H), 6.50 (dd, J
) 2.8, 8.7 Hz, 1H), 6.58 (d, J ) 8.7 Hz, 1H), 6.62 (d, J ) 2.6
Hz, 1H), 7.05 (dd, J ) 1.2, 2.6 Hz, 1H), 7.12 (dd, J ) 1.5, 2.6
Hz, 1H); FTIR (KBr) 1640; mass spectrum m/ z 296 (M+), 281
(M+ - Me). Anal. Calcd for C19H24N2O: C, 76.99; H, 8.16; N,
9.45. Found: C, 77.16; H, 8.23; N, 9.47.
Ack n ow led gm en t. We acknowledge helpful discus-
sions with Prof. K. Yoshida of Kochi University and Mr.
S. Hamaguchi, Miss. A. Niimi, and Mr. Y. Endo for their
assistance with this work.
X-r a y Da ta . The crystal data and details of the experiment
are reported in Table 6. The lattice constants were determined
by a CAD4 indexing program and refined by a least-squares
method with the angular setting of 15 reflections (32 ° < 2θ <
42 °). Data were collected on an ENRAF-Nonius CAD4
diffractometer using a crystal with dimension of 0.4 × 0.2 ×
0.15 mm. The diffraction power of the crystal is rather poor
so that the diffraction spot could hardly be observed at the
higher region (2θ > 100 °). A total of 6483 reflections were
J O951907W
(26) Sheldrick, G. M. SHELXS-86. Program for Crystal Structure
solution, Institute fur Anoganishe Chemie der Universitat, Germany.
(27) Sheldrick, G. M. SHELX-76. Program for crystal structure
determination, University of Cambridge.
(28) The author has deposited atomic coordinates for structure 3
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.
measured in the range 2θ < 141°, of which 3703 with F0
g