JPH09241197A - Optically active calixarene compound and identification of optical isomer using the compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound bonding with one of optical isomers of a specific asymmetric compound to remarkably change its color and, accordingly, useful for the identification, production management, etc., of a compound having an optical isomer important as pharmaceuticals, agrochemicals, etc. SOLUTION: This calixarene compound is expressed by formula I (X is a bivalent organic group containing an optically active organic group; R<1> to R<4> are each H, a 1-4C alkyl or a 1-4C alkoxy). The group X in formula I is preferably an optically active binaphthyl or an organic group of formula II ((n) is 0 or 1). The analysis with the compound comprises e.g. the mixing of the compound of formula I with a solution containing an optical isomer and the identification of the optical isomer from the change in the absorption spectrum caused by the mixing.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a compound that recognizes an asymmetric compound and develops a color, and can be used for analysis of a compound whose optical isomers such as pharmaceuticals and agricultural chemicals are important, and their identification and production. It can be used for management, etc.

[0002]

2. Description of the Related Art Most biological substances are asymmetric compounds whose enantiomers do not overlap with the original molecule, and many biologically active substances are also asymmetric compounds. Therefore, drugs, agricultural chemicals, biochemical reagents, etc. Are mostly asymmetric compounds. Also,
Other than pharmaceuticals and agricultural chemicals, asymmetric compounds are used for ferroelectric liquid crystals. In such a case, the optical isomers show completely different physiological activities, or the racemic form has a reduced function or no expression at all.

As described above, there are many fields in which asymmetric compounds are used, but it is not easy to quantify optical isomers. A method that is often used is spectroscopic method.When the solution of an asymmetric compound has absorption, the circular dichroism, which is the difference between the absorption of right circularly polarized light and that of left circularly polarized light, is A general method is to measure the rotation (optical rotation) of linearly polarized light. This device is precise, and the device is expensive and not easy as compared with the measurement of visible and ultraviolet absorption spectra. As a matter of course, it's not what you can see the difference in appearance.

It is also practiced to use asymmetric recognition in which an asymmetric compound interacts with only one of its optical isomers to cause some change. Asymmetric recognition is one of the most basic processes that occur in the living body, and therefore many synthetic model compounds such as chiral crown ethers have been proposed so far. To date, several host-guest combinations showing high asymmetric recognition function have been reported, for example, crown ether-organic ammonium ion.
(EB Kyba, K. Koga, LR Sousa, MG Siegel, a
nd DJ Cram, J. Am. Chem. Soc., 95, 2692 (197
3)), porphyrin-amino acid (K. Konishi, K. Yahara,
H. Toshishige, T. Aida, and S. Inoue, J. Am. Chem.
Soc., 116, 1337 (1994)), all of which are realized by skillfully combining interactions such as hydrogen bonding, pi-electron-pi-electron interaction, ion-dipole, and steric complementarity. are doing.

On the other hand, various methods have been reported for evaluating the chiral recognition ability of these hosts. For example, detection of a complex by mass spectrum using a fast atom bombardment (FAB) method (M. Sawada, Y. Takai, H. Yamada, S. Hi
rayama, T. Kaneda, T. Tanaka, K. Kamada, T. Mizook
u, S. Takeuti, K. Ueno, K. Hirose, Y. Tobe, and K.
Naemura, J. Am. Chem. Soc., 117, 7726 (1995), M.S.
awada, Y. Okumura, M. Shizuma, Y. Takai, Y. Hidaka,
H. Yamada, T. Tanaka, T. Kaneda, K. Hirose, S. Mi
sumi, and S. Takahashi, J. Am. Chem. Soc., 115, 73
81 (1993)) is an efficient method that utilizes the high-sensitivity characteristics of mass spectrometry, and an example of carrying out optical resolution by chromatography by supporting a host on silica gel (LR Sous
a, GDY Sogah, DH Hoffman, and DJ Cram,
J. Am. Chem. Soc., 100, 4569 (1978)), an example of liquid-liquid extraction of a guest by a host investigated from changes in the signal on the host side in NMR (EP Kyba, JM Timko, L.
J. Kaplan, F. de Jong, GW Gokel, and DJ Cra
m, 100, 4555 (1978)).

Of these, the simple, easy-to-understand, and most interesting example is a study utilizing changes in optical characteristics. This has many advantages such as that complex formation information can be detected in the form of change in absorbance or fluorescence, and a method for calculating an association constant indicating host-guest affinity has been established in an easy form. What is interesting is that it has the potential to be used as an asymmetric discrimination reagent due to its simplicity. Irie et al. (M. Irie, T. Yorozu, and K. Haya
shi, J. Am. Chem. Soc., 100, 2236 (1978), T. Yoroz
u, K. Hayashi, and M. Irie, J. Am. Chem. Soc., 10
3, 5480 (1981)) shows the fluorescence of chiral 1,1'-binaphthyl,
By adding chiral amine, which is a fluorescence quencher,
Introducing an example of asymmetric selective extinction, Shinkai et al. (TD
James, KRAS Sandanayake, and S. Shinkai, Na
ture, 374, 345 (1995)) is a compound that incorporates a sugar-binding arylboronic acid into a chiral 1,1'-binaphthyl compound, and introduces an example in which quenching of binaphthyl occurs due to asymmetric recognition of sugar. are doing. Both of these two examples are based on the fact that the quenching process of fluorescence by electrons or charge transfer has a large steric effect together with electronic elements, and it is not recognition at the receptor but at the optical functional site, so to speak. It can be noted as one of the epoch-making methods in this field because of the asymmetric discrimination of. On the other hand, some examples have been reported that show an optical asymmetric recognition response mainly in the visible region, such as a change in color tone. For example, an example of incorporating a crown ether as a unit that binds ammonium ions to a cholesterol molecule exhibiting liquid crystallinity (T.
Nishi, A. Ikeda, T. Matsuda, and S. Shinkai, J. Che
m. Soc., Chem. Commun., 1991, 339, S. Shinkai, TN
ishi, and T. Matsuda, Chem. Lett., 1991, 437), changes in the pitch of cholesteric liquid crystals occur with the addition of amino acid or chiral amine hydrochlorides or chiral mandelate salts. Accordingly, there is a difference of up to 60 nm in the wavelength of the reflected light, but it is not so effective considering the complexity of sample preparation and the slow response of the liquid crystal. In addition, Kaneda et al. Have reported many compounds that incorporate an azophenol dye into the chiral crown ether skeleton and exhibit an optical asymmetric recognition response to amines (for example, T. Kaneda, K. Hirose, and S. Misumi, J.
Am.Chem. Soc., 111, 742 (1989)), the maximum wavelength change of R and S is 10n even when the largest difference is obtained.
It is only m, and it is difficult to distinguish the difference with the naked eye.

[0007]

As described above, it has been necessary to use a precise and expensive device for identifying optical isomers of conventional asymmetric compounds. Further, even when a change in color or fluorescence due to asymmetric recognition is used, the change is minute, and it is difficult to quantify it with high precision or to visually and easily recognize the difference. The present invention provides a novel compound capable of undergoing a large change in color upon binding with an optical isomer of an asymmetric compound, and capable of taking a large concentration range of a binding partner.

[0008]

Means for Solving the Problems The present inventors have found that the compound shown below binds to one optical isomer of a specific asymmetric compound to cause a large change in color, and has arrived at the present invention. . That is, the gist of the first invention is a calixarene compound represented by the following general formula (I).

[0009]

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(In the formula, X is a divalent organic group containing an optically active organic group, and R ^{1 to} R ⁴ are each a hydrogen atom or a carbon atom which may have a substituent. The second aspect of the present invention is a method of mixing a solution containing an optical isomer and the calixarene compound, and distinguishing the optical isomer from the change in absorption spectrum at that time. is there.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. In the above general formula (I), X is preferably a divalent organic group containing an optically active binaphthyl group, and particularly preferably a divalent organic group represented by the following structural formula (II).

[0012]

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(In the formula, n represents 0 or 1.) The organic group represented by the structural formula (II) has no asymmetric carbon, but two naphthalene rings cannot rotate freely.
It becomes an asymmetric compound. This compound can be synthesized from calixarene in which four phenols are linked by methylene. The optically active X moiety may be introduced by a route such that the optically active material is used and the optical activity does not disappear, or a method of synthesizing in a racemic form and subsequently performing optical resolution is also possible. . Furthermore, the lengths of the two linking groups between the optically active site and the calixarene ring may be the same or different, but when the guest molecule is bound, the effect on the two dye sites becomes different and expression occurs. Since the effect becomes more remarkable, different ones are preferable. That is, in the above structural formula (II), n is preferably 0 rather than 1.

The compound of the present invention binds to an asymmetric compound of a specific organic amine, and its absorption spectrum is largely changed. At this time, depending on the arrangement of X (R or S), the asymmetric organic amine to be bound also has a large difference in the binding constant between R and S, and the rate at which the absorption spectrum changes greatly. Since this change is so large that it can be visually discriminated, it is possible to easily discriminate optical isomers.

Also, by preparing both R and S for the compound of the present invention, the mixing ratio of R and S of the target organic amine can be determined. For this, a mixture of R and S of the organic amine is divided into two, R and S of the compound of the present invention are allowed to act separately, and the change in the absorption spectrum thereof is measured.

[0016]

【Example】

 Example 1

[0017]

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Synthesis of

[0019]

[Chemical 6]

Synthesis of 2-Bromoethyl Tetrahydropyranyl Ether 10 3,4-Dihydro-2H-pyran (3.03 g, 0.036 mol) and concentrated hydrochloric acid in 2-bromoethanol (3 g, 0.024 mol) as a catalytic amount (half a drop). ) Was added and stirred at room temperature for 1 hour. Tribenzylamine was added until pH reached 5-6.5 and vacuum distillation (80 ° C,
0.2Torr), 10 of colorless transparent liquid 4.29g (yield 85
%) Got. ¹³ C-NMR (50MHz, CDCl ₃ ) δ (ppm) 98.9, 67.5, 62.2, 3
0.7, 30.4, 25.3, 19.2.

Synthesis of 2- (chloroethoxy) ethyl tetrahydropyranyl ether 11 2- (2-chloroethoxy) ethanol (10.0 g, 72.2 mo
3,4-dihydro-2H-pyran (10.2 g, 118 mmol) and concentrated hydrochloric acid (catalytic amount (half drop)) were added to (l) and stirred at room temperature for 1 hour.
Tribenzylamine was added until the pH became 5-6.5, and distillation under reduced pressure (87-88 ° C, 0.5 Torr) yielded 16.1 g (98% yield) of 11 as a colorless transparent liquid. ¹³ C-NMR (50 MHz, CDCl ₃ ) δ (ppm) 99.0, 71.4, 70.7,
66.7, 62.3, 42.7, 30.6, 25.4, 19.5.

P-tert-butylcalix [4] arene 4
Synthesis of p-tert-butylphenol 3 (25.0 g, 0.17 mol) in 37
% Formaldehyde aqueous solution (15.5 mL, 0.19 mol) and
NaOH (0.3 g, 7.5 mmol) was added, and the mixture was stirred at 120 ° C for 2 hr. After cooling to room temperature, phenyl ether (250 mL)
Was added and dissolved, and the temperature was slowly raised while flowing nitrogen into the reaction mixture to remove water, and then the mixture was refluxed (259 ° C.) for 2 hours. After allowing to cool, ethyl acetate (275 mL) was added, and the mixture was stirred overnight, and the formed precipitate was filtered off. The obtained precipitate was washed twice with ethyl acetate (25 mL), once with acetic acid (50 mL), and twice with water (50 mL) to give compound 4 as a white powder (13.9 g, yield 52%). )Obtained. ¹ H-NMR (400 MHz, CDCl ₃ ) δ (ppm) 10.33 (s, 4H, Ar-
OH), 7.05 (s, 8H, Ar-H), 4.38-3.40 (m, 8H, ArCH ₂ A
r), 1.21 (s, 36H, t-Bu); MS, m / z 648 (M +); mp 320
-322 ° C.

Synthesis of calix [4] arene 5 To a dry toluene solution (280 mL) of compound 4 (30.0 g, 45.1 mmol) was added phenol (20.4 g, 0.217 mol) and aluminum chloride (32.0 g, 0.240 mol), Under nitrogen, 5
The mixture was stirred at 0 ° C for 2 hours. 0.2N HCl aqueous solution (500 mL) was added to the reaction mixture, the mixture was stirred, and then the organic layer was separated.
It was washed (toluene 280 mL -water 280 mL). After heating and concentrating, methanol was added to precipitate a precipitate, which was filtered off and recrystallized in a chloroform-methanol solvent system to obtain 15.6 g (yield 79%) of compound 5. ¹ H-NMR (200 MHz, CDCl ₃ ) δ (ppm) 10.10 (s, 4H, Ar-
OH), 7.70 (d, J = 7.5Hz, 8H, Ar-H), 6.75 (t, J = 7.5Hz,
4H, Ar-H), 4.60-3.30 (brd, 8H, ArCH ₂ Ar); MS, m / z
424 (M +).

(S) -2 '-(2- (2-tetrahydropyranyloxy)
Synthesis of (ethoxy) -1,1'-binaphthyl-2-ol 7 of (S) -1,1'-bi-2-naphthol (500 mg, 1.75 mmol) 6
Dry acetone solution (10 mL) in anhydrous potassium carbonate (310 m
g, 2.24 mmol) and heated under reflux for 1 hour under nitrogen, then 1-bromo-2- (2-tetrahydropyranyloxy) ethane 1
0 dry acetone solution (2 mL) was added. After heating under reflux for 46 hours, the solvent was distilled off under reduced pressure, and methylene chloride (25 m
The target substance was extracted with (L) -water (25 mL). The organic layer was washed twice with water, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure before column chromatography (packing agent wakogel C-3
428 mg (yield 59%) of the target compound 7 was obtained by separating and purifying with 00, a developing solvent ethyl acetate: chloroform = 1: 9).

¹ H-NMR (200 MHz, CDCl ₃ ) δ (ppm) 8.01
(d, J = 9.1Hz, 2H, Naph-H4), 7.89-7.81 (m, 2H, Naph
-H5), 7.49 (d, J = 9.2Hz, 1H, Naph-H3), 7.48 (d, J =
9.0Hz, 1H, Naph-H3 '), 7.36 (pseudo-t, 2H, Naph-H6),
7.29-7.02 (m, 4H, Naph-H7,8), 5.16 (brs, 1H, Naph
-OH), 4.28-3.13 (m, 9H, OCH ₂ , THP-H), 1.60-1.23
(m, 4H, THP-H).

(S) -2 '-(2-hydroxyethoxy) -2- (2- (2-
Synthesis of (hydroxyethoxy) ethoxy) -1,1'-binaphthyl 8 A solution of compound 7 (669 mg, 1.61 mmol) in dry DMF (10 m
L) 60% NaH (129 mg, 3.23 mmol) and NaI (484 m
g, 3.23 mmol) and heated with stirring at 80 ° C for 1 hour, and then dried 1- (2-chloroethoxy) -2- (2-tetrahydropyranyloxy) ethane 11 (673 mg, 3.23 mmol) in a dry DMF solution ( 2 mL) was added and the mixture was heated under reflux for 24 hours. After the reaction was completed, a few drops of water were added, the solvent was distilled off under reduced pressure, and the mixture was extracted with methylene chloride (30 mL) -water (30 mL).
Washed twice with L). Methanol (30 mL) and concentrated hydrochloric acid (2 mL) were added to this organic layer, and the mixture was stirred at room temperature for 3.5 hours. Saturated aqueous sodium hydrogen carbonate solution (ca. 20 mL)
After neutralizing with, the organic layer was washed 3 times with water and the solvent was distilled off under reduced pressure.
Column chromatography (Wakogel C-300 packing material,
By separating and purifying with a developing solvent (ethyl acetate),
549 mg of the target compound 8 in the form of yellow tar (yield 81%)
Obtained.

¹ H-NMR (200 MHz, CDCl ₃ ) δ (ppm) 7.97
(d, J = 9.2Hz, 2H, Naph-H4), 7.88 (d, J = 8.0Hz, 2H, N
aph-H5), 7.47 (d, J = 9.0Hz, 1H, Naph-H3), 7.42 (d,
J = 9.1Hz, 1H, Naph-H3 '), 7.37-7.29 (pseudo-t, 2H, N
aph-H6), 7.27-7.17 (pseudo-t, 2H, Naph-H7), 7.14-
7.07 (m, 2H, Naph-H8), 4.36-3.11 (m, 12H, OCH2),
3.63 (brs, 1H, OH), 3.62 (brs, 1H, OH).

(S) -2 '-(2-Tosyloxyethoxy) -2- (2- (2-
Synthesis of (tosyloxyethoxy) ethoxy) -1,1'-binaphthyl 9 p-toluenesulfonic acid chloride (2000 mg, 10.5 mmo
l) dry pyridine solution (5 mL) was stirred at 0 ° C. for 1 hour, compound 8 (549 mg, 1.31 mmol) in cold dry pyridine solution (3 mL) was added, and the mixture was stirred under ice cooling for 1 hour. After leaving it in the freezer for 2 days, the reaction mixture was poured into crushed ice and stirred for 1 hour to decompose unreacted TsCl, and then methylene chloride (30 mL) was added and stirred well. The organic layer was washed 3 times with 3N aqueous hydrochloric acid solution (30 mL), 5%
The extract was washed once with an aqueous sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. By vacuum-drying the obtained tar-like substance, 819 mg (yield 86%) of the tar-like target compound 9 was obtained.

¹ H-NMR (200 MHz, CDCl ₃ ) δ (ppm) 7.95
(d, J = 9.0Hz, 1H, Naph-H4), 7.88 (d, J = 8.7Hz, 1H,
Naph-H4 '), 7.84-7.78 (m, 2H, Naph-H5), 7.70 (d, J =
8.3Hz, 2H, Ts-H), 7.44-7.03 (m, 10H, Naph-H and Ts-
H), 4.16-2.98 (m, 12H, OCH2), 2.42 (s, 3H, Ar-CH
3), 2.36 (s, 3H, Ar-CH3).

Synthesis of (S) -1,1'-binaphthyl-substituted calix [4] crown 2a Calix [4] arene 5 (478 mg, 1.13 mmol) dry
Toluene solution (95 mL) was added with 60% sodium hydride (45 m
g, 1.13 mmol) was added, and the mixture was heated under reflux for 1 hr. Tosylate 9 (819 mg, 1.13 mmo for the cloudy reaction mixture)
l) dry acetonitrile (1 mL) -dry toluene (40 mL)
(mL) Add the mixed solution slowly (for 2 minutes) and leave it as it is.
Heated to reflux for an hour. During that time, 60% sodium hydride (45 mg, 1.13 mmol) was added twice every 12 to 18 hours for a total of 90 times.
mg (2.26 mmol) was added. After the reaction is complete, add 1% of the reaction solution.
Wash twice with aqueous hydrochloric acid (150 mL) and once with water (150 mL).
In that case, methanol (10 mL) was added), the organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid is subjected to column chromatography (filler
After separating and purifying with Wakogel C-300, a developing solvent of methylene chloride, impurities that could not be further separated were GPC (column Shodex K-2000 + K-2001, Showa Denko, developing solvent).
Compound 2 as a white solid by removing with chloroform)
307 mg (34% of yield) of a were obtained.

¹ H-NMR (400 MHz, CDCl ₃ ) δ (ppm) 7.99
(d, J = 9.0Hz, 1H, Naph-H4), 7.89 (d, J = 8.0Hz, 1H,
Naph-H5), 7.77 (d, 1H, Naph-H5 '), 7.53 (s, 1H, Ar
-OH), 7.52 (d, J = 8.9Hz, 1H, Naph-H3), 7.44 (d, J =
9.0Hz, 1H, Naph-H4 '), 7.35 (s, 1H, Ar-OH), 7.32 (t,
J = 8.1Hz, 1H, Naph-H6), 7.31 (t, J = 8.1Hz, 1H, Nap
h-H6 '), 7.24-7.19 (m, 4H, Naph-H7,7' and Naph-H8,
8 '), 7.01 (d, J = 9.0Hz, 1H, Naph-H3'), 7.09-6.84
(m, 7H, Ar-H), 6.74-6.60 (m, 7H, Ar-H), 4.64-3.58
(m, 12H, CH ₂ ), 4.55 and 3.35 (ABq, J = 13.2Hz, 2H,
ArCH ₂ Ar), 4.22and 3.35 (ABq, J = 13.4Hz, 2H, ArCH ₂ A
r), 4.25 and 3.34 (ABq, J = 13.1Hz, 2H, ArCH ₂ Ar), 3.
22 and 2.48 (ABq, J = 13.2Hz, 2H, ArCH ₂ Ar); MS (E
I), m / z 805 (M + 1).

Synthesis of a novel pigment body 1a derived from (S) -1,1'-binaphthyl-substituted calix [4] crown 2a (S) -1,1'-binaphthyl-substituted calix [4] crown 2a (2
00 mg, 0.248 mmol) in acetonitrile (100 mL)
DBU (9 mL) and 4-amino-m-cresol (122 mg,
0.991 mmol) was added and dissolved, then an aqueous solution (50 mL) of potassium ferricyanide (653 mg, 1.983 mmol) was added all at once, and the mixture was stirred overnight at room temperature. The reaction solution was neutralized with 10% acetic acid aqueous solution under ice cooling, and chloroform (100 mL) -1%
It was extracted with a hydrochloric acid aqueous solution (100 mL). The organic layer was washed twice with a 1% aqueous hydrochloric acid solution (100 mL) and three times with water (100 mL), and the solvent was evaporated under reduced pressure. The red residue was separated and purified by column chromatography (filler neutral alumina activity, developing solvent chloroform) and impurities that could not be separated were separated by GPC (column Shodex K-2000 + K-200).
1 Removed with Showa Denko, developing solvent chloroform) and reprecipitated with chloroform (1 mL) -hexane (25 mL) to obtain 138 mg (yield 53%) of compound 1a as a red powder.

¹ H-NMR (400 MHz, CDCl ₃ , 299.3 K) δ (p
pm) 8.06 (brs, 1H, Ar-OH), 7.91 (s, 1H, Ar-OH),
7.79 (d, 1H, J = 8.0Hz, Naph-H5 '), 7.58 (d, J = 9.0
Hz, 1H, Naph-H4), 7.54 (d, J = 9.0Hz, 1H, Naph-H3),
7.4-7.1 (m, 6H, Naph-H7,7 ', 8,8' and Naph-H6,6 '),
7.13 (d, J = 9.0Hz, 1H, Naph-H3 '), 7.11 (d, J = 1
0.2Hz, 1H, Quinoid-Hb), 6.94-6.64 (m, 10H, ArH),
6.60 (brs, 1H, Quinoid-Hc), 6.55-6.52 (m, 2H, Quin
oid-Ha and Hc '), 6.45 (dd, J = 2.2Hz and 10.3Hz, 1
H, Quinod-Ha '), 4.64-3.36 (m, 12H, CH ₂ ), 4.27 and
3.39 (ABq, J = 12.9Hz, 2H, ArCH ₂ Ar), 4.62 and 3.37
(ABq, J = 13.4Hz, 2H, ArCH ₂ Ar), 4.28 and 3.37 (AB
q, J = 12.9Hz, 2H, ArCH ₂ Ar), 3.33 and 2.54 (ABq, J
= 16.0Hz, 2H, ArCH ₂ Ar), 2.38 (s, 3H, Ar-CH ₃ ), 2.2
9 (s, 3H, Ar-CH ₃ ); ¹³ C-NMR (100MHz, CDCl ₃ , 297.3
K) d (ppm) 188.3 (Quinone carbonyl-C), 188.2 (Quin
one carbonyl-C), 156.6, 156.2, 154.7, 154.2,153.2,
152.6, 151.6, 151.5, 150.0, 149.9, 134.2, 133.7, 1
33.2, 133.0, 132.9, and 132.1 (Ar-C (Quaternary)),
131.8 (Quinoid-C), 131.6 (Quinoid-C), 130.3, 130.
2, 129.5, 129.4, 129.3, 129.2, 129.1,129.0, 128.7,
and 128.5 (ArC), 127.9 (Naph-C5 '), 127.8 (Naph-C
5), 126.4, 126.2, 125.6, 125.4, and 125.3 (ArC), 1
23.9 (Naph-C), 123.8 (Naph-C), 122.8 (Calixarene-
C), 122.7 (Calixarene-C), 122.5 (Calixarene-C), 12
2.4 (Calixarene-C), 121.0 (ArC), 120.3 (ArC), 116.
9 (Naph-C3 '), 115.8 (Naph-C3), 76.2 (OCH ₂ ), 75.4
(OCH ₂ ), 70.3 (OCH ₂ ), 70.0 (OCH ₂ ), 68.6 (OCH ₂ ), 31.3
(ArCH ₂ Ar), 31.1 (ArCH ₂ Ar), 29.9 (ArCH ₂ Ar), 18.3
(ArCH ₃ ), 18.2 (ArCH ₃ ) .MS (FAB +), m / z = 1045 (M ++
1); CD (100% EtOH), λmax (nm) (Δε (mol ^-1 dm ³ cm
^-1 )), 237 (+145), 226 (-63.8), 214 (+60.0). AnalCa
lcd for C ₆₈ H ₅₆ O ₉ N ₂ 1 / 2H ₂ O: C, 77.48; H, 5.45; N,
2.66. Found: C, 77.49; H, 5.47; N, 2.65.

Compound 1a was added to 515.5% in 100% ethanol.
nm (ε; 14500 mol^-1 dm^Three cm^-1) Indicates maximum absorption and red
However, when a primary amine is added as a guest, the acid
Shows long-wavelength side shift due to base reaction, around 650 nm
New absorption appears and the color tone changes from purple to blue. Ma
This compound was +145 mol at 237 nm in 100% ethanol.
^-1 dm^Three cm^-1, -63.8 mol at 226 nm^-1 dm^Three cm^-1, 214 nm
To +60.0 mol^-1dm^Threecm ^-1Since it showed CD activity of
The optical activity of the raw material (S) -1,1'-binaphthol is in the process of synthesis.
Not lost in.

Example 2 FIG. 1 shows an absorption spectrum obtained by adding (R) -phenylglycinol to compound 1a. At 652.5 nm, a new absorption band that appears to be based on the acid-base reaction of phenol and amine appeared, and it was observed that the absorption intensity of this band increased as the amount of amine added increased. On the other hand, the absorption band of undissociated indophenol (515.5 nm) is 22 nm with the increase of absorption intensity while maintaining the isosbestic point around 505 nm by the addition of amine.
Shows a long-wavelength side shift and has a new absorption at 538 nm.

Next, the same measurement was performed by changing the guest to the antipode (S) -phenylglycinol. The result is shown in FIG. Very interestingly, the guest from the R-body
The change in the absorption spectrum was significantly suppressed by changing to the S-form, and visually, when the R-form was added, the color changed from red to purple, whereas when the S-form was added, it remained red. Met. As shown here, the addition of the S- form was almost saturated at a 1000-fold molar ratio, and the long-wavelength side shift of the short-wavelength band (515.5 nm) observed with the R- form was observed. Was not done. The fact that the reaction of the absorption spectrum changes due to the change in the absolute structure of the guest suggests that compound 1a may have an asymmetric recognition function for phenylglycinol. Considering the change in the shorter wavelength band, the R-form showed a good change, whereas the S-form showed that the change was completely suppressed even when the guest was added in a considerably excessive amount.

Example 3 The Benesi-Hildebrand plot, which can be easily calculated using the change in absorbance, was used for the association constant. Benesi-Hildebrand when the guest was (R) -phenylglycinol
The plot is shown in Figure 3. Since each point has a good linear relationship, it was found that compound 1a and (R) -phenylglycinol form a 1: 1 complex.

Example 4 An attempt was made to detect a complex by mass spectrometry in order to directly confirm the formation of the complex. Regarding the ionization method, we decided to use the fast atom bombardment (FAB) method, which is a soft ionization method, because the host and guest are bound by a non-covalent force. The method is as follows. That is, a chloroform solution of host 1a (0.03 mol dm ^-3 , 20 mL) and a methanol solution of guest (R) -phenylglycinol (0.5 mol dm ^-3 , 12 m
L) was mixed in a vial, the solvent was removed, and 3-nitrobenzyl alcohol (20 mL) was added as a matrix ([1a] = 0.03 mol dm ^-3 , [Guest] / [Host] = 10 /
1), stirred well and left for two nights. Take 1 mL of this FA
It was placed on the target for B and measured. As a result, in addition to m / z 1045 (M + 1) which is the molecular ion peak of the host, m / z 1
A small peak was observed at 181. The host's mass number is 1044, the guest's mass number is 137, and the sum of the two is 1181. Therefore, the small peak observed is considered to be derived from the complex.

Example 5 100% ethanol solution of compound 1a (2.0 x 10 ^-5 mol d
An amino acid equivalent to 500 eq. to m ⁻³ ) was added as a solid. At this time, most of the amino acid does not dissolve but precipitates, so the absorption spectrum was measured using the supernatant.

As a result, an optical asymmetric recognition response function was found for phenylglycine which is one of the amino acids. That is, the color tone of the solution remained red even when (S) -phenylglycine was added as a guest, whereas when (R) -phenylglycine was added, it was visually recognizable as magenta. Showed a change. The absorption spectrum is shown in FIG. Example 6

[0041]

Embedded image

A compound solution 2b (80 mg, 0.094 mmol) in acetonitrile (40 mL) was added to DBU (1,8-Diazabicyclo [5.
4.0] -7-undecene) (3.7 mL) was added and the mixture was stirred while 4-
Amino-m-cresol (34.7 mg, 0.282 mmol) was added and dissolved. Potassium ferricyanide (187
An aqueous solution (19 mL) of mg, 0.564 mmol) was slowly added dropwise, and the mixture was reacted overnight. When the reaction is complete, cool on ice at 10%
Neutralize the reaction solution with aqueous acetic acid and add chloroform (30 m
L) -1% hydrochloric acid aqueous solution (40 mL) extracted. 1% organic layer
The solution was washed 4 times with an aqueous hydrochloric acid solution (70 mL) and once with water (90 mL), and the solvent was evaporated under reduced pressure. The red residue was separated and purified by column chromatography (Wakogel FC-40, packing solvent, distilled chloroform containing 5% acetone → distilled chloroform containing 8% acetone), and impurities that could not be separated were separated by GPC (column Shodex K-2000 + K-200
1 Removed with Showa Denko, developing solvent chloroform) and reprecipitated with chloroform (1 mL) -hexane (25 mL) to obtain 17 mg of red powdered compound 1b (yield 17%).

¹ H-NMR (200 MHz, CDCl ₃ ) δ (ppm) 8.31
(brs, 2H, Ar-OH), 7.95 (d, J = 9.0Hz, 2H, Naph-H4),
7.86 (d, J = 7.6Hz, 2H, Naph-H5), 7.47 (d, J = 9.0Hz,
2H, Naph-H3), 7.33 (pseudo-t, 2H, Naph-H6), 7.26-
7.17 (m, 2H, Ar-H), 7.07 (d, J = 10.2Hz, 2H, Quinoid-
Hb), 6.97 (pseudo-t, J = 7.8Hz, 2H, Naph-H7), 6.90-
6.89 (m, 2H, Ar-H), 6.82 (d, J = 7.4Hz, 2H, Ar-H),
6.77 (d, J = 2.4Hz, Ar-OH), 6.66 (d, J = 2.4Hz, 2H, Ar
-H), 6.53 (m, 2H, Quinoid-Hc), 6.42 (dd, J = 10.2Hz
and 2.3Hz, 2H, Quinoid-Ha), 4.52-3.16 (m, 16H, OCH
₂ ), 4.43 and 3.37 (ABq, J = 12.9Hz, 4H, ArCH ₂ Ar), 4.3
8 and 3.37 (ABq, J = 13.2Hz, 4H, ArCH ₂ Ar), 2.28 (s,
6H, Ar-CH ₃ ); CD (100% EtOH), λmax (nm) (Δε (mol
^-1 dm ³ cm ^{- 1} )), 236 (+193), 225 (-107).

Example 7 The R-form and S-form of phenylglycinol were added to the ethanol solution of the compound of Example 6. The results are shown in FIGS. 5 and 6, respectively. The compound of Example 6 exhibits an asymmetric recognition response, although to a lesser extent than compound 1a. Therefore, based on this result, Benesi-
When the association constant was calculated using the Hildebrand plot, it was 17 ± 12
It was calculated to be dm ³ mol ^-1 .

[0045]

INDUSTRIAL APPLICABILITY By using the present invention, optical isomers of asymmetric compounds can be easily detected.

[Brief description of drawings]

FIG. 1 shows changes in absorption spectrum when (R) -phenylglycinol was added to a 2 × 10 ⁻⁵ M ethanol solution of the compound of Example 1.

FIG. 2 shows changes in absorption spectrum when (S) -phenylglycinol was added to a 2 × 10 ⁻⁵ M ethanol solution of the compound of Example 1.

FIG. 3 is a Benesi-Hildebrand plot of the complex of the compound of Example 1 and (R) -phenylglycinol. The reciprocal of the concentration of (R) -phenylglycinol is plotted on the horizontal axis, and the reciprocal of the change in absorbance is plotted on the vertical axis.

FIG. 4 shows changes in absorption spectrum (a) and (S) -phenylglycine when 500 equivalents of (R) -phenylglycine was added to a 2 × 10 ⁻⁵ M ethanol solution of the compound of Example 1. It shows a change (b) in the absorption spectrum when added.

FIG. 5 shows a change in absorption spectrum when (R) -phenylglycinol was added to a 2 × 10 ⁻⁵ M ethanol solution of the compound of Example 5.

FIG. 6 shows a change in absorption spectrum when (S) -phenylglycinol was added to a 2 × 10 ⁻⁵ M ethanol solution of the compound of Example 6.

Claims (4)

[Claims] 1. A calixarene compound represented by the following general formula (I): Embedded image (In the formula, X is a divalent organic group containing an optically active organic group, and R ^{1 to} R ⁴ are each a hydrogen atom or an alkyl group having 1 to 4 carbon atoms which may have a substituent. Alternatively, it represents an alkoxy group.) 2. The calixarene compound according to claim 1, wherein X contains an optically active binaphthyl group. 3. The calixarene compound according to claim 1, wherein X is a divalent organic group represented by the following structural formula (II). Embedded image (In the formula, n represents 0 or 1.) 4. A solution containing an optical isomer, and claims 1-3.
A method of mixing the calixarene compound according to any one of 1. to identify an optical isomer by a change in absorption spectrum at that time.