JP6874990B2 - Method for determining chirality and optical purity of optically active chiralamine compound using colorimetric detection type chiral sensor - Google Patents

Description

The present invention relates to a simple and practical method for determining chirality and optical purity of an optically active chiralamine compound using a colorimetric chiral sensor composed of a spiral poly (diphenylacetylene) compound.

Organic compounds have exactly the same physical and chemical properties, such as boiling point, melting point, and solubility, but there are many optical isomers with different physiological activities. In the technical field such as medicine, the difference in pharmacological activity due to the ease of binding to a specific receptor in the living body has been well studied, and it is remarkable in terms of drug efficacy and toxicity among optical isomers (that is, enantiomers). It is widely known that there are many cases where there is a difference. Under these circumstances, along with the selective synthesis technology of optical isomers and the separation technology of optical isomers from racemates, the sensing technology of optical isomers (technology for determining the chirality of optical isomers) is also attracting attention. Has been done. That is, when a compound having an optical isomer is synthesized or provided, it is possible to determine with high accuracy which chirality the compound has, whether it is a racemate, or the like, and it is possible to easily identify the chirality. The development of methods has become an extremely important issue.

Many studies have been reported on chirality discrimination using circular dichroism (CD) spectra that directly reflect molecular asymmetry, and chirality discrimination using NMR shift reagents, chiral HPLC, etc. However, it cannot be said that it is a simple sensing method because it is very expensive as a chirality detection device. One of the simplest methods for identifying chirality is a chirality sensing method that utilizes visible color changes.

As such a technique, a fluorescent chiral sensor has been reported that utilizes the characteristics of a host-guest complex formation equilibrium reaction by a fluorescent host compound (or polymer) having an optically active crown ether structure (Patent Documents 1 and 2). These are chirality sensing methods based on molecular recognition by complex formation between an optically active crown ether structure, which is a host compound, and a chiral primary amine, which is a guest compound (identification target). There remains a problem that it is easily affected by conditions such as concentration at the time of measurement, and it is necessary to introduce an expensive optically active functional group into the guest recognition site of the host compound.

The present inventors have recently prepared an optically active chiralamine compound having a spiral structure in which the optically active chiralamine compound is wound in one direction according to the following formula (I):

[During the ceremony,
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each a hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, substituted Indicates a cycloalkyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, a tri-substituted silyl group, a tri-substituted syroxy group or an acyloxy group which may be substituted; Indicates an integer of 10 or more. ]
By reacting with a poly (diphenylacetylene) compound represented by (1) to amidate and observing changes in the color tone and fluorescence of the solution of the derivative, a method for sensitively identifying the chirality of an optically active chiralamine compound was found (. Patent Document 3). According to this method, the derivative exhibits a large non-linear response in the low optical purity region (that is, 0 to 10% ee), and highly accurate detection in this region is possible, but the high optical purity is in high demand. The region (ie, 90-100% ee) and other optical purity regions (ie, 10-90% ee) showed no non-linear responsiveness and could hardly be identified. In general, the nonlinear response region is often determined at the stage of molecular design of the chiral sensor, so it was thought that this method could not be used to determine the optical purity of optically active chiralamine compounds other than the low optical purity region. ..

Japanese Patent No. 3950117 Japanese Patent No. 4545370 Japanese Unexamined Patent Publication No. 2016-155781

Against this background, it is practical that the chirality and optical purity of various types of optically active chiralamine compounds can be easily and accurately identified (determined) inexpensively and sensitively in any optical purity region. There is an increasing demand for the development of various chirality sensing methods.

An object of the present invention is to utilize a spiral poly (diphenylacetylene) compound which does not have an expensive optically active functional group by itself to specialize the chirality and optical purity of various kinds of optically active chiralamine compounds. Provided is a simple and practical chirality sensing method capable of identifying and determining by utilizing a visible change in color (and fluorescence) in any optical purity region without using a flexible device. It is to be.

As a result of diligent studies under such circumstances, the present inventors have the following formula (I): which has a unidirectionally wound spiral structure.

[During the ceremony,
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each a hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, substituted Indicates a cycloalkyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, a tri-substituted silyl group, a tri-substituted syroxy group or an acyloxy group which may be substituted; Indicates an integer of 10 or more. ]
The poly (diphenylacetylene) compound represented by (hereinafter, also referred to as “Compound (I)”) or a salt thereof is condensed with each of two or more known optically active chiralamine compounds having different optical purity. A step of preparing two or more kinds of amidated compounds and preparing a solution in which each compound is dissolved in two or more kinds of mixed solvents having different mixing ratios of two specific kinds of solvents as a standard sample. Compound (I) or a salt thereof was condensed with an optically active chiralamine compound (test target compound) having unknown kirarity and optical purity to prepare a solution prepared by dissolving the amidated compound in any of the above-mentioned mixed solvents. Then, by observing the color tone and / or fluorescence intensity of the solution in comparison with the standard sample, the clarity and optical purity of the optically active chiralamine compound to be tested can be visually or inexpensively measured in any optical purity region. For the first time, we have found that it is useful as a practical clarity sensing method that can be identified (determined) more easily and accurately, and have completed the present invention.

That is, the present invention is as follows.
[1] Equation (I) having a one-way spiral structure:

[During the ceremony,
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each a hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, substituted Indicates a cycloalkyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, a tri-substituted silyl group, a tri-substituted syroxy group or an acyloxy group which may be substituted; Indicates an integer of 10 or more. ]
A step of condensing each of a poly (diphenylacetylene) compound represented by (diphenylacetylene) or a salt thereof and two or more known optically active chiralamine compounds having different optical purity to obtain two or more amidated compounds.
The amidated two or more kinds of compounds are mixed into a mixed solvent consisting of a first solvent which is an organic solvent having a specific dielectric constant of less than 10 and a second solvent which is an organic solvent having a specific dielectric constant of 15 or more and 40 or less. In the step of preparing each dissolved solution as a standard sample, a compound amidated by condensing the compound of the above formula (I) or a salt thereof with an optically active chiralamine compound of an unknown subject whose kirarity and optical purity are unknown. By observing the color tone and / or fluorescence intensity of the solution of the amidated compound in comparison with the standard sample, the step of preparing the solution dissolved in the mixed solvent, and the optically active chiralamine compound of the test subject. A method for determining the kirarity and optical purity of an optically active chiralamine compound, which comprises a step of determining the kirarity and optical purity of the optically active chiralamine compound.
[2] The method according to [1] above, which comprises a step of selecting a mixed solvent of the solution prepared as the standard sample from two or more mixed solvents having different mixing ratios.
[3] The first solvent is chloroform, dichloromethane, 1,1,2,2-tetrachloroethane, tetrahydrofuran or 1,4-dioxane, and the second solvent is acetone, methylethylketone, N, N-dimethyl. The method according to [1] or [2] above, which is formamide or N, N-dimethylacetamide.
[4] The above [1] or [2], wherein the first solvent is 1,1,2,2-tetrachloroethane or tetrahydrofuran, and the second solvent is acetone or N, N-dimethylformamide. The method described.
[5] The method according to any one of [1] to [4] above, wherein the color tone and / or fluorescence intensity of the solution is comparatively observed visually or by a photographic image.
[6] Equation (II) having a one-way spiral structure:

[During the ceremony,
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each a hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, substituted Indicates a cycloalkyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, a tri-substituted silyl group, a tri-substituted syroxy group or an acyloxy group which may be substituted;
RNH represents a chiral amino group; and n represents an integer greater than or equal to 10. ]
A first solvent and a relative permittivity of a poly (diphenylacetylene) compound represented by (hereinafter, also referred to as “compound (II)”) or a salt thereof, which is an organic solvent having a relative permittivity of less than 10. A mixed solvent solution comprising a second solvent which is an organic solvent having a value of 15 or more and 40 or less.
[7] The first solvent is chloroform, dichloromethane, 1,1,2,2-tetrachloroethane, tetrahydrofuran or 1,4-dioxane, and the second solvent is acetone, methylethylketone, N, N-dimethyl. The solution according to [6] above, which is formamide or N, N-dimethylacetamide.
[8] The solution according to [6] above, wherein the first solvent is 1,1,2,2-tetrachloroethane or tetrahydrofuran, and the second solvent is acetone or N, N-dimethylformamide.

The compound (II) obtained by condensing an optically active chiralamine compound and the compound (I) to amidate the compound (II), which is an organic solvent having a specific dielectric constant of less than 10, and a specific solvent having a specific dielectric constant of 15 or more and 40 or less. A solution dissolved in a mixed solvent consisting of a second solvent, which is an organic solvent, has a color tone (ultraviolet / visible absorption) and fluorescence intensity only by changing the mixing ratio of the first solvent and the second solvent. Since the optical purity region having a large non-linear response can be freely shifted, the demand is high, but the high optical purity region (90 to 100% ee), in which it has been difficult to determine the optical purity visually or by the fluorescence spectrum. It is also possible to determine the kirarity and optical purity of the optically active chiralamine compound with very high resolution. Further, according to the present invention, the chirality and optical purity of various kinds of optically active chiralamine compounds can be analyzed after taking a picture with an inexpensive camera or smartphone without using an expensive and special measuring device (RGB). It is possible to accurately identify the difference in the excess ratio of enantiomers only by comparing and observing with the color tone of a standard sample solution having known optical purity by the calibration curve (calibration curve created by analysis) or by visual inspection.

a is a compound (II-1-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) and tetrahydrofuran / N, N-dimethylformamide 90:10. ^{It is an absorption spectrum of a solution (polymer concentration: 1.0 × 10 -3} M) dissolved in a mixed solvent prepared by the mixing ratio of, and b is compound (II-1-Y) (Y = S100, S80, A solution of S60, S40, S20, S0, R20, R40, R60, R80, R100) dissolved in a mixed solvent prepared with tetrahydrofuran / N, N-dimethylformamide at a mixing ratio of 90:10 (polymer concentration: 1). It is a fluorescence spectrum of .0 × 10 ^{-3 M).} a is a compound (II-1-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) and tetrahydrofuran / N, N-dimethylformamide at 100: 0. ^{Maximum fluorescence intensity when the fluorescence spectrum of a solution (polymer concentration: 1.0 × 10 -3} M) dissolved in a mixed solvent prepared at a mixing ratio of 90:10 and 85:15 was measured at an excitation wavelength of 540 nm. A graph in which the values are plotted is shown, in which b is a compound (II-1-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100), tetrahydrofuran / N, ^{The fluorescence spectrum of a solution (polymer concentration: 1.0 × 10 -3} M) in which N-dimethylformamide was dissolved in a mixed solvent prepared at a mixing ratio of 100: 0, 90:10 and 85:15 was obtained at an excitation wavelength of 350 nm. The graph which plotted the maximum value of the fluorescence intensity at the time of measurement is shown. Compound (II-1-Y) (Y = S100 (a), S80 (b), S60 (c)) showing a large color change in FIG. 2a was mixed with tetrahydrofuran / N, N-dimethylformamide 100: A solution dissolved in a solvent of 0 (polymer concentration: 1.0 × 10 ^-3 M) and compound (II-1-Y) (Y = R20 (d), R40 (e), R60 (f)) were added. , Tetrahydrofuran / N, N-dimethylformamide is dissolved in a mixed solvent prepared at a mixing ratio of 90:10 (polymer concentration: 1.0 × 10 ^-3 M). Compound (II-1-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) mixed with tetrachloroethane / acetone at a mixing ratio of 100: 0 and 80:20. The graph which plotted the absorption intensity of 520 nm when the absorption spectrum of the solution (polymer concentration: 1.0 × 10 ^{-3 M) dissolved in the mixed solvent prepared in 3 was measured is shown.} Compound (II-1-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) and tetrahydrofuran / acetone at 100: 0, 80:20, 60:40. A graph showing the absorption intensity at 540 nm when the absorption spectrum of ^{the solution (polymer concentration: 1.0 × 10 -3} M) dissolved in the mixed solvent prepared at the mixing ratio of 40:60 was measured is shown. A solution of compound (II-1-Y) (Y = R90, R92, R94, R96, R98, R100) dissolved in a mixed solvent prepared by mixing tetrahydrofuran / acetone at a mixing ratio of 30:70 (polymer concentration: 1). The absorption spectrum of .0 × 10 ^-3 M) is shown. Compound (II-1-Y) (R90 (a), R92 (b), R94 (c), R96 (d), R98 (e), R100 (f)) mixed with tetrahydrofuran / acetone at 30:70. The photograph of the solution (polymer concentration: 1.0 × 10 ^{-3 M) dissolved in the mixed solvent prepared by the ratio is shown.} Compound (II-1-Y) (R90 (a), R92 (b), R94 (c), R96 (d), R98 (e), R100 (f)) mixed with tetrahydrofuran / acetone at 30:70. The graph which plotted the RGB component extracted from the photograph (FIG. 7) of the solution (polymer concentration: 1.0 × 10 ^{-3 M) dissolved in the mixed solvent prepared by the ratio is shown.} Compound (II-2-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) in a mixed ratio of chloroform / acetone at 100: 0 and 95: 5. The graph which plotted the absorption intensity of 520 nm when the absorption spectrum of the solution (polymer concentration: 1.0 × 10 ^{-3 M) dissolved in the prepared mixed solvent was measured is shown.} Compound (II-3-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100), tetrahydrofuran / N, N-dimethylformamide 100: 0 and 90: The graph which plotted the absorption intensity of 560 nm when the absorption spectrum of ^{the solution (polymer concentration: 1.0 × 10 -3} M) dissolved in the mixed solvent prepared by the mixing ratio of 10 was measured is shown. Compound (II-1-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) and tetrahydrofuran / dimethyl sulfoxide at 100: 0, 96.5: 3. The graph which plotted the absorption intensity of 550 nm when the absorption spectrum of ^{the solution (polymer concentration: 1.0 × 10 -3} M) dissolved in the mixed solvent prepared with the mixing ratio of 5 and 95: 5 was measured is shown.

The details of the present invention will be described below.

(Definition)

As used herein, the term "halogen atom" means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

In the present specification, the "alkyl (group)" means a linear or branched-chain alkyl group having one or more carbon atoms, and is preferably C when there is no particular limitation on the carbon number range. _{It is a 1-20} alkyl group, with a C _1-12 alkyl group being more preferred and a C _1-6 alkyl group being particularly preferred.

In the present specification, "C _1-20 alkyl (group)" means an alkyl group having 1 to 20 carbon atoms in a linear or branched chain, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl. , Se-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl , Octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, eikosyl and the like.

In the present specification, "C _1-12 alkyl (group)" means an alkyl group having 1 to 12 carbon atoms in a linear or branched chain, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl. , Se-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl , Octyl, nonyl, decyl, undecyl, dodecyl and the like.

In the present specification, "C _1-6 alkyl (group)" means an alkyl group having 1 to 6 carbon atoms in a linear or branched chain, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl. , Se-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, etc. Can be mentioned.

In the present specification, the “cycloalkyl (group)” means a cyclic alkyl group, and is preferably a C _3-8 cycloalkyl group unless the carbon number range is particularly limited.

In the present specification, "C _3-8 cycloalkyl (group)" means a cyclic alkyl group having 3 to 8 carbon atoms, and for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. Can be mentioned. Of these, the C _3-6 cycloalkyl group is preferable.

In the present specification, "alkoxy (group)" means a group in which a linear or branched alkyl group is bonded to an oxygen atom, and the carbon number range is not particularly limited, but C _1-6 alkoxy is preferable. It is a group.

In the present specification, "C _1-6 alkoxy (group)" means an alkoxy group having 1 to 6 carbon atoms in a linear or branched chain, and for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, and the like. Examples thereof include isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy and the like. Of these, the C _1-4 alkoxy group is preferable.

In the present specification, "alkylthio (group)" means a group in which an alkyl group of a linear or branched chain is bonded to a sulfur atom, and the carbon number range is not particularly limited, but C _1-6 alkylthio is preferable. It is a group.

In the present specification, "C _1-6 alkylthio (group)" means an alkylthio group having 1 to 6 carbon atoms in a linear or branched chain, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, and the like. Examples thereof include isobutylthio, sec-butylthio, tert-butylthio, pentylthio, isopentylthio, neopentylthio, hexylthio and the like. Of these, a C _1-4 alkylthio group is preferable.

In the present specification, the "alkylsulfonyl (group)" means a group in which a linear or branched alkyl group is bonded to a sulfonyl group, and the carbon number range is not particularly limited, but C _{1-6 is preferable.} It is an alkylsulfonyl group.

In the present specification, the “C _1-6 alkyl sulfonyl (group)” means a group in which an alkyl group having 1 to 6 carbon atoms in a straight chain or a branched chain is bonded to a sulfonyl group. Ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, isopentylsulfonyl, neopentylsulfonyl, 1-ethylpropylsulfonyl, hexylsulfonyl, isohexylsulfonyl, 1 , 1-Dimethylbutylsulfonyl, 2,2-dimethylbutylsulfonyl, 3,3-dimethylbutylsulfonyl, 2-ethylbutylsulfonyl and the like.

In the present specification, the "arylsulfonyl (group)" means a group in which an aryl group is bonded to a sulfonyl group, and the carbon number range is not particularly limited, but a C _6-10 arylsulfonyl group is preferable.

In the present specification, the "C _6-10 aryl sulfonyl group" _{means a group in which a "C 6-10} aryl group" is bonded to a sulfonyl group, for example, phenylsulfonyl, 1-naphthylsulfonyl, 2-naphthylsulfonyl. And so on.

In the present specification, the "alkylsulfonyloxy (group)" means a group in which an alkylsulfonyl group is bonded to an oxygen atom, and the carbon number range is not particularly limited, but a C _1-6 alkylsulfonyloxy group is preferable. Is.

In the present specification, "C _1-6 alkyl sulfonyloxy (group)" _{means a group in which a C 1-6} alkyl sulfonyl group is bonded to an oxygen atom, and for example, methyl sulfonyloxy, ethyl sulfonyl oxy, propyl sulfonyl. Oxy, isopropylsulfonyloxy, butylsulfonyloxy and the like can be mentioned.

In the present specification, the "arylsulfonyloxy (group)" means a group in which an arylsulfonyl group is bonded to an oxygen atom, and the carbon number range is not particularly limited, but a C _6-10 arylsulfonyloxy group is preferable. Is.

In the present specification, "C _6-10 arylsulfonyloxy (group)" _{means a group in which a C 6-10} arylsulfonyl group is bonded to an oxygen atom, for example, phenylsulfonyloxy, 1-naphthylsulfonyloxy, and the like. 2-naphthylsulfonyloxy and the like can be mentioned.

In the present specification, the "acyl" means an alkanoyl or an aloyl, and the carbon number range is not particularly limited, but a C _1-7 alkanoyl group or a C _7-11 aloyl is preferable.

In the present specification, the "C _1-7 alkanoyl (group)" is a linear or branched formyl or alkylcarbonyl having 1 to 7 carbon atoms, and is, for example, formyl, acetyl, propionyl, butyryl, and the like. Examples thereof include isobutyryl, pentanoyl, hexanoyl, heptanoyle and the like.

In the present specification, "C _7-11 aloyl (group)" is an arylcarbonyl having 7 to 11 carbon atoms, and examples thereof include benzoyl and the like.

In the present specification, the "acyloxy (group)" means an alkanoyl group or a group in which an aroyl group is bonded to an oxygen atom, and the carbon number range is not particularly limited, but a C _1-7 alkanoyloxy group or a C 1-7 alkanoyloxy group is preferable. It is a C _7-11 alloyloxy group.

In the present specification, "C _1-7 alkanoyloxy (group)" includes, for example, formyloxy, acetoxy, ethylcarbonyloxy, propylcarbonyloxy, isopropylcarbonyloxy, butylcarbonyloxy, isobutylcarbonyloxy, sec-butylcarbonyl. Examples thereof include oxy, tert-butylcarbonyloxy, pentylcarbonyloxy, isopentylcarbonyloxy, neopentylcarbonyloxy, and hexylcarbonyloxy.

In the present specification, _{examples of the "C 7-11} aloyloxy (group)" include benzoyloxy, 1-naphthoyloxy, 2-naphthoyloxy and the like.

In the present specification, "aryl (group)" means a monocyclic or polycyclic (condensed) hydrocarbon group exhibiting aromaticity, and specifically, for example, phenyl, 1-naphthyl, and the like. It shows a _C6-14 aryl group such as 2-naphthyl, biphenylyl, 2-anthryl and the like. Of these, a C _6-10 aryl group is preferable.

In the present specification, "C _6-10 aryl (group)" means, for example, phenyl, 1-naphthyl, 2-naphthyl, and phenyl is particularly preferable.

In the present specification, the "aralkyl (group)" means a group in which an aryl group is substituted with an alkyl group, and the carbon number range is not particularly limited, but C _7-14 aralkyl is preferable.

In the present specification, "C _7-14 aralkyl (group)" _{means a group in which "C 1-4} alkyl group" is substituted with "C _6-10 aryl group", for example, benzyl, 1-phenyl. Ethyl, 2-phenylethyl, (naphthyl-1-yl) methyl, (naphthyl-2-yl) methyl, 1- (naphthyl-1-yl) ethyl, 1- (naphthyl-2-yl) ethyl, 2-( Examples thereof include naphthyl-1-yl) ethyl, 2- (naphthyl-2-yl) ethyl, and biphenylylmethyl.

As used herein, the term "tri-substituted silyl (group)" means a silyl group substituted with _{three identical or different substituents (eg, C 1-6} alkyl group, C _{6-10 aryl group, etc.). However, the group includes a trialkylsilyl group (preferably a triC 1-6} alkylsilyl group) such as a trimethylsilyl group, a triethylsilyl group, a triisopropylsilyl group, and a tert-butyldimethylsilyl group, and a tert-butyldiphenylsilyl. A group, a triphenylsilyl group and the like are preferable.

As used herein, the term "tri-substituted syroxy (group)" means a group in which a tri-substituted silyl group is bonded to an oxygen atom. _{As the group, a trialkylsiloxy group (preferably a triC 1-6} alkylsiloxy group) such as a trimethylsiloxy group, a triethylsiloxy group, a triisopropylsiloxy group and a tert-butyldimethylsiloxy group is preferable.

As used herein, the term "protected amino group" means an amino group protected by a "protecting group". As the “protecting group”, for example, the protecting group of the amino group described in Protective Groups in Organic Synthesis, John Wiley and Sons (1980) can be used, and for example, C _1-6 alkyl group, C _7-14. Protecting groups such as aralkyl group, C _6-10 aryl group, C _1-7 alkanoyl group, C _7-14 aralkyl-carbonyl group, tri C _1-6 alkylsilyl group and the like can be mentioned. The above protecting groups _{may be further substituted with halogen atoms, C 1-6} alkyl groups, C _1-6 alkoxy groups or nitro groups. Specific examples of the protecting group for the amino group include methyl, acetyl, trifluoroacetyl, pivaloyl, tert-butoxycarbonyl, benzyloxycarbonyl and the like.

In the present specification, "may be substituted" means that it may have one or more substituents, and the "substituent" includes (1) halogen atom, (2). ) Nitro, (3) cyano, (4) C _1-6 alkyl, (5) C _3-8 cycloalkyl, (6) C _1-6 alkoxy, (7) C _6-10 aryl, (8) C _{7 -14} Aralkyl, (9) C _1-7 Alkanoyloxy, (10) C _7-11 Aloyloxy, (11) C _1-7 Alkanoyl, (12) C _7-11 Alkyl, (13) Azide, (14) C _1-6 alkylthio, (15) C _6-10 arylthio, (16) _{carbamoyl optionally substituted with C 1-6} alkyl group, (17) C _1-6 alkylsulfonyloxy group, (18) C _{6- Examples thereof include a 10} arylsulfonyloxy group, (19) a tri-C _1-6 alkylsilyl group, and (20) a protected amino group. Among them, halogen atom, C _1-6 alkyl, C _1-6 alkoxy, acetyl, formyl, carbamoyl, azide, trimethylsilyl, triethylsilyl, triisopropylsilyl, tert-butyldimethylsilyl, dimethylamino, acetylamino, tert-butoxycarbonyl. Amino, benzyloxycarbonylamino and the like are preferable, and a halogen atom is particularly preferable. Further, when a plurality of substituents are present, each substituent may be the same or different.

The substituent may be further substituted with the above substituent. The number of substituents is not particularly limited as long as it can be substituted, but is preferably 1 to 5, more preferably 1 to 3. When a plurality of substituents are present, each substituent may be the same or different. The substituents are also further C _1-6 alkyl group, C _3-8 cycloalkyl group, C _6-10 aryl group, C _7-14 aralkyl group, halogen atom, carboxy group, protected amino group, carbamoyl group, It may be substituted with a cyano group, a nitro group, an oxo group or the like. The number of substituents is not particularly limited as long as it can be substituted, but is preferably 1 to 5, more preferably 1 to 3. When a plurality of substituents are present, each substituent may be the same or different.

In the present specification, the "one-way winding spiral structure" may be any spiral structure that is biased to either right-handed or left-handed, and is preferably a completely right-handed or left-handed spiral structure. A compound having a "unidirectionally wound helical structure" exhibits optical activity due only to a biased helical structure, even if the molecule does not have an optically active functional group.

In the present specification, "optical activity" means a property of rotating plane polarized light of light, that is, a state having optical rotation ability. Preferably, it is in an optically pure state.

In the present specification, the "chiral amine compound" means an organic amine compound having central chirality, axial chirality or surface chirality, and for example, central chirality (asymmetric center, that is, asymmetric center). Examples include organic amine compounds having (carbon atoms).

In the present specification, the "optically active chiralamine compound" is a compound having a property of rotating plane polarized light of light, that is, an optical rotation ability, and is an organic having central chirality, axial chirality or planar chirality. Examples include amine compounds. Preferably, an amine compound having one optically pure asymmetric carbon atom having a molecular weight of 500 or less is applicable to the present invention, and for example, both optically pure enantiomers are commercially available. 1-Phenylethylamine, 1-Cyclohexylethylamine, 1- (1-naphthyl) ethylamine, 1- (2-naphthyl) ethylamine, sec-butylamine, 1-phenyl-2- (p-tolyl) ethylamine, 1- (p) -Trill) ethylamine, 1- (4-methoxyphenyl) ethylamine, β-methylphenethylamine, 2-amino-1-butanol, 2-amino-1,2-diphenylethanol, 1-amino-2-indanol, 2-amino -1-phenyl-1,3-propanediol, 2-amino-1-propanol, leucinol, phenylalaninol, 2-phenylglycinol, valinol, norephedrine, methioninol, 1-benzyl-3-aminopyrrolidine, 2- (Methoxymethyl) pyrrolidine, 1-methyl-2- (1-piperidinomethyl) pyrrolidine, 1- (2-pyrrolidinomethyl) pyrrolidine, 1-acetyl-3-pyrrolidinol, 1-benzyl-3-pyrrolidinol, 1-acetyl- Examples thereof include optically active compounds of chiral compounds such as 3-pyrrolidinol, 1-methyl-3-pyrrolidinol, quinidine, quinine, quincholine, quincoridine, cinconidine, cinconin, and amino acids with protected carboxy groups. The "optically active chiralamine compound" includes not only optically pure compounds but also compounds having low optical purity. The low molecular weight compound may be a liquid or a solid, and is preferably a liquid.

In the present specification, "ee" is an abbreviation for enantiomeric excess, and represents the optical purity of a chiralamine compound. “Ee” is calculated by subtracting the amount of substance of the smaller enantiomer from the amount of substance of the larger enantiomer, dividing by the total amount of substance, and multiplying by 100, and is represented by “% ee”.

In the present specification, "optically pure" means a state exhibiting an optical purity of 99% ee or more.

As used herein, the term "enantiomer" means an optically antipode that has a different configuration of all asymmetric carbon atoms in an optically active low molecular weight compound, and is referred to as an optically active low molecular weight compound. It constitutes a pair of optical isomers that are in a relationship of right hand and left hand with each other. Specifically, for example, when the optically active compound is (R)-(+)-1-phenylethylamine, the enantiomer is (S)-(-)-1-phenylethylamine.

In the present specification, the "racemic mixture" means a compound in a state in which it does not exhibit optical rotation due to the presence of equal amounts of two types of enantiomers of chiral amine compounds.

In the present specification, the “chiral sensor” means a substance (compound or the like) capable of measuring and discriminating chirality and optical purity of an optically active chiralamine compound with high sensitivity. In the present specification, performing measurement and discrimination using a "chiral sensor" is referred to as "chiral sensing".

In the present specification, "colorimetric detection" is a method in which a measurement substance or a reaction product is changed into a color-developing substance, and the degree of color development is colorimetrically quantified by absorbance using visible light having an appropriate wavelength. .. The "specific color detection" in the present invention also includes a detection method using a visible change in color, a fluorescence detection method using a change in fluorescence intensity, and a detection method using an ultraviolet / visible absorption spectrum.

In the present specification, "RGB" is a kind of color expression method, and is a kind of additive mixture that reproduces a wide range of colors by mixing three primary colors of red (Red), green (Green), and blue (Blue). is there. RGB is an acronym for the three primary colors. It is used for image reproduction with digital cameras and the like.

In the present specification, "non-linear responsiveness" means the optical purity of the optically active chiralamine to be tested (identified) and the absorbance and / or fluorescence intensity of the specific absorption region of the poly (diphenylacetylene) into which the chiralamine has been introduced. Means that the changes in are not proportional. Since it is possible to increase the amount of change in absorbance and / or fluorescence intensity in a specific optical purity region as compared with the case of linear response (when there is a proportional relationship), in order to improve the accuracy of chiral sensing. Used as a technique.
In general, it is extremely difficult to predict from the molecular structure whether or not a chiral sensor molecule exhibits non-linear responsiveness. Furthermore, as far as the present inventors know, there are no reported examples in which non-linear responsiveness is exhibited by selecting a solvent (type of solvent, mixing ratio, etc.).

(Colorimetric detection type chiral sensor of the present invention)
The colorimetric detection type chiral sensor of the present invention has the following formula (I), which has a spiral structure wound in one direction around the compound (I), that is, the polymer main chain.

[During the ceremony,
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each a hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, substituted Indicates a cycloalkyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, a tri-substituted silyl group, a tri-substituted syroxy group or an acyloxy group which may be substituted; Indicates an integer of 10 or more. ]
It is a colorimetric detection type chiral sensor composed of a poly (diphenylacetylene) compound represented by, a salt thereof, or a solvate thereof.

Examples of the salt of compound (I) include a salt with an inorganic base, a salt with an organic base, a salt with an amino acid, and the like.

Examples of the salt with the inorganic base include sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt and the like.
Examples of salts with organic bases include methylamine, diethylamine, trimethylamine, triethylamine, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, tris (hydroxymethyl) methylamine, dicyclohexylamine, N, N'-dibenzylethylenediamine, and guanidine. , Salts with pyridine, picolin, choline, cinconin, meglumin and the like.
Examples of the salt with the amino acid include salts with lysine, arginine, aspartic acid, glutamic acid and the like.

The solvate of compound (I) or a salt thereof is a solvate of compound (I) or a salt thereof in which a molecule of a solvent is coordinated, and hydrates are also included. For example, a hydrate of compound (I) or a salt thereof, a Japanese ethanol product, a Japanese dimethyl sulfoxide product, and the like can be mentioned.

Hereinafter, each group of compound (I) will be described.

^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each a hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, substituted It represents a cycloalkyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, a tri-substituted silyl group, a tri-substituted siloxy group or an acyloxy group which may be substituted.

^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are preferably each hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, It is an alkoxy group, a trialkylsilyl group or a trialkylsiloxy group which may be substituted, and more preferably, a C _1-6 alkyl group which may be independently substituted with a hydrogen atom, a halogen atom and a halogen atom, respectively. _{, C 1-6} alkoxy group, tri-C _1-6 alkylsilyl group or tri-C _1-6 alkylsiloxy group which may be substituted with a halogen atom, and among them, a hydrogen atom or a halogen atom is particularly preferable.

^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4',} preferably, ^{R 1} and ^{R 1} ', ^{R 2} and ^{R 2', R 3} and ^{R 3} 'and ^{R 4} and ^{R 4'} are each the same group. ^{R 1, R 1 ', R} 2, R 2', all the ^{R 3,} R 3 'R ⁴ and ^{R 4'} may be the same group.

n is an integer of 10 or more, preferably an integer of 100 or more and 10000 or less.

As the compound (I), the following compounds are suitable.
[Compound (IA)]
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each a hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, substituted also alkoxy group, trialkylsilyl group or trialkylsiloxy, and ^{R 1} and ^{R 1} ', ^{R 2} and ^{R 2', R 3} is a ^{R 3} 'and ^{R 4} and ^{R 4',} respectively identical Compound (I), wherein n is an integer greater than or equal to 10.

A more suitable compound (I) is the following compound.
[Compound (IB)]
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} may independently each a hydrogen atom, a halogen atom, optionally substituted by a halogen atom _{C 1- A 6} alkyl group, a C _1-6 alkoxy group optionally substituted with a halogen atom, a tri C _1-6 alkylsilyl group or a tri C _1-6 alkylsiloxy group, and R ¹ and R ¹ ', R ² and ^{R 2} ', ^{R 3} and ^{R 3'} and ^{R 4} and ^{R 4} 'are each be the same group; and n is 10 to 10,000 integer compound (I).

A more suitable compound (I) is the following compound.
[Compound (IC)]
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each independently a hydrogen atom or a halogen atom, and ^{R 1} and ^{R 1} ', ^{R 2} and ^{R 2} ', ^{R 3} and ^{R 3'} and ^{R 4} and ^{R 4} 'are each be the same group; and n is 10 to 10,000 integer compound (I).

The number average degree of polymerization of compound (I) (the average number of diphenylethylene units contained in one molecule) is 10 or more, preferably 100 or more, and there is no particular upper limit, but it is easy to handle that it is 10000 or less. It is desirable in that respect.

In addition, compound (I) ^{may be labeled with an isotope (for example, 3} H, ² H (D), ¹⁴ C, ³⁵ S, etc.).

(Synthesis of compound (I))
The method for producing the compound (I) is not particularly limited, but the compound (I) can be produced according to a method known per se or a method similar thereto described in Patent Document 3 (Japanese Unexamined Patent Publication No. 2016-155781).

(Method for identifying chirality of optically active chiralamine compound by compound (I) and determining optical purity)

Compound (I) is condensed with an optically active chiralamine compound to be tested (identified) (two molecules of the same optically active chiralamine compound having the same optical purity are condensed with one molecule of compound (I)). When amidated by, there is a significant change in the color tone and / or fluorescence intensity of the solution in which the amide compound is dissolved in a specific mixed solvent, depending on the absolute configuration and slight difference in optical purity of the test subject. Is observed. Then, by observing the remarkable change in the color tone and / or the fluorescence intensity visually with a camera, a smartphone, or visually, the absolute three-dimensional arrangement and the optical purity of the optically active chiralamine compound to be identified can be accurately and accurately identified and determined. It is possible.

The method for determining the chirality and optical purity of an optically active chiralamine compound to be tested (identified) in the present invention includes the following steps.

(Step 1) Two or more compounds (eg, each optical purity region (eg, 90)) which are amidated by condensing each of compound (I) and two or more known optically active chiralamine compounds having different optical purity. A step of obtaining (a compound obtained by condensing a chiralamine compound in which the optical purity is changed every 2% ee) in the range of% ee to 100% ee).
(Step 2) The amidated two or more compounds are separated from the first solvent which is an organic solvent having a relative permittivity of less than 10 and the second solvent which is an organic solvent having a relative permittivity of 15 or more and 40 or less. A step of preparing a solution dissolved in each of the mixed solvents as a standard sample.
(Step 2') A step of selecting a mixed solvent of the solution prepared as the standard sample from two or more mixed solvents having different mixing ratios (that is, selecting a mixed solvent exhibiting nonlinear responsiveness in a target optical purity region). Process),
(Step 2'') A step of creating a calibration curve from the absorbance and / or fluorescence intensity of each solution of the standard sample, or the RGB analysis result of a photographic image.
(Step 3) A compound obtained by condensing compound (I) with an optically active chiralamine compound of a test subject whose chirality and optical purity are unknown and amidizing the compound is subjected to a non-linear response in the mixed solvent (that is, a target optical purity region). Steps of preparing a solution dissolved in a mixed solvent exhibiting properties,
(Step 4) The color tone and / or fluorescence intensity of the solution of the amidated compound is visually or by RGB analysis of the photographic image of the standard sample (absorbance and / or fluorescence intensity of the standard sample, or RGB analysis result of the photographic image). A step of determining the chirality and optical purity of the optically active chiralamine compound of the test subject by comparative observation with (calibration curve prepared from).

The optically active chiral amine capable of distinguishing the kirarity is not particularly limited, but is preferably primary amines (eg, 1- (1-naphthyl) ethylamine, 1-phenylethylamine, 2-butylamine, 1-cyclohexyl). Optical of amino alcohols (eg, 2-phenylglycinol, phenylalaninol, 2-aminopropanol, etc.), amino acid derivatives (eg, t-butyl esters of amino acids such as alanine, phenylalanine, leucine, etc.) Activators are mentioned, and among them, compounds having a primary amino group are particularly suitable.

The compound (II), which is a condensate of the compound (I) and the optically active chiralamine compound to be identified, is the method known per se or the same as that described in Patent Document 3 (Japanese Unexamined Patent Publication No. 2016-155781). It can be manufactured according to the method.

Compound (II) is dissolved in a mixed solvent consisting of a first solvent which is an organic solvent having a relative permittivity of less than 10 and a second solvent which is an organic solvent having a relative permittivity of 15 or more and 40 or less, and the compound (II) is dissolved. ) Is prepared, a change in the color tone and / or fluorescence intensity of the solution is observed due to the difference in the clarity and optical purity of the chiralamino group in the compound (II). Then, in the present invention, surprisingly, by adjusting the selection of the first solvent and the second solvent constituting the mixed solvent used when preparing the solution and the mixing ratio thereof, the identification object is identified. It has been found that it is possible to adjust the ultraviolet / visible absorption and fluorescence intensity so as to exhibit non-linear responsiveness in any optical purity region regardless of the high or low optical purity of the optically active chiralamine compound. As a result, the chirality of the optically active chiralamine compound to be identified and the optical purity can be identified by image analysis (RGB analysis processing) or visual inspection of a photograph taken by an inexpensive camera or smartphone, as described in Examples described later. It is possible to make a simple and highly accurate determination just by observing. Specifically, as described in Example 5 described later, a standard sample containing a specific concentration of an optically active chiralamine compound (known sample) to be identified having two or more different enantiomeric excesss (ee) is provided. , Created for each ee, performed image analysis (RGB analysis) processing of the photograph of each sample, and created a calibration curve as shown in FIG. 8 to obtain the optical purity of the identification target whose optical purity is unknown. It is possible to determine with high accuracy.

In addition, the method for determining the chirality and optical purity of the optically active chiralamine compound of the present invention also includes a method for determining the optical purity of the optically active chiralamine compound in combination with the data of the ultraviolet / visible absorption spectrum.

Examples of the first solvent include organic solvents having a relative permittivity of less than 10, and specifically, for example, chloroform (4.89), dichloromethane (9.02), 1,1,2,2-tetra. Low polar organic solvents such as chloroform (8.42), tetrahydrofuran (7.47), 1,4-dioxane (2.10) are suitable. Of these, 1,1,2,2-tetrachloroethane or tetrahydrofuran is particularly preferable. The numerical values in parentheses indicate the relative permittivity of each solvent at 25 ° C. (The numerical values are described in Tadashi Okuyama, Organic Chemical Reactions and Solvents, Maruzen (1998)).

Examples of the second solvent include organic solvents having a relative permittivity of 15 or more and 40 or less. Specifically, for example, acetone (21.4), methyl ethyl ketone (18.9), N, N-dimethylformamide ( Highly polar organic solvents such as 37.1), N, N-dimethylacetamide (38.3) are suitable. Of these, acetone or N, N-dimethylformamide is particularly preferable. The numerical values in parentheses indicate the relative permittivity of each solvent at 25 ° C. (The numerical values are described in Tadashi Okuyama, Organic Chemical Reactions and Solvents, Maruzen (1998)).

As the second solvent, an organic solvent having a relative permittivity of more than 40 (eg, dimethyl sulfoxide (relative permittivity at 25 ° C.: 46.7 (Tadashi Okuyama, Organic Chemical Reactions and Solvents, Maruzen (1998)). When))) is used, even a small amount of addition to the first solvent causes a large shift in the optical purity region (region that can be measured with high accuracy) showing non-linear responsiveness, resulting in a measurement error. There is a possibility (see Example 8). On the other hand, when an organic solvent having a relative permittivity of 15 or more and 40 or less is used, the shift of the optical purity region exhibiting nonlinear responsiveness is gentle, so that there is an advantage that measurement error is unlikely to occur.

In the method for determining the chirality and optical purity of the optically active chiralamine compound of the present invention, since the compound (I) and the optically active chiralamine (identification target) are strongly bonded by a covalent bond, conventionally known molecular recognition (non-recognition). Compared to a chiral sensor that uses covalent interaction), it is not necessary to consider the effects of chemical equilibrium, etc., so it does not depend on measurement conditions (concentration, temperature, etc.), has good reproducibility, and is a chirality to be identified. The tee can be identified.

Further, according to the method for determining the chirality and optical purity of the optically active chiralamine compound of the present invention, it is not necessary for the compound (I), which is the chiral sensor to be used, to introduce an expensive optically active functional group, and it is simple and simple. It has the advantage that the chirality of a unidirectionally wound spiral can be introduced into the main chain at low cost, and also with the first solvent constituting the mixed solvent used when preparing the solution. By selecting the second solvent and adjusting the mixing ratio thereof, it is possible to freely exhibit non-linear responsiveness to ultraviolet / visible absorption and fluorescence intensity regardless of the optical purity of the optically active chiral amine compound to be identified. It also has the advantage of being controllable. Therefore, the determination of the optical purity, which is usually difficult to visually identify, can be accurately determined by the extremely simple operation of selecting the first solvent and the second solvent constituting the mixed solvent and changing the mixing ratio thereof. It is a practical chirality sensing method that does not require expensive and special measuring equipment in that it can be determined.

Hereinafter, the present invention will be described in detail with reference to Examples, but the present invention is not limited thereto.

Average molecular weight is converted to polystyrene by gel permeation chromatography (JASCO High Performance Liquid Chromatography Pump PU-2080, JASCO UV-970, JASCO Column Oven CO-1560, JASCO Column KF-805L). Calculated in.
Circular dichroism (CD) measurement is JASCO circular dichroism dispersometer J-725, ultraviolet-visible absorption measurement is JASCO ultraviolet-visible spectrophotometer V-570, and fluorescence measurement is JASCO spectrofluorescence photometer. This was done using FP-6300.
An iPhone 6S manufactured by Apple Inc. was used for photography. RGB analysis of the captured image was performed using the application Pixel Picker.
"Room temperature" in the following examples usually indicates about 10 ° C to about 25 ° C. The ratio shown in the mixed solvent indicates the volume ratio unless otherwise specified. % Indicates the weight% unless otherwise specified.

Example 1
Analysis sample for plotting (synthesis of compound (II-1-Y))

(1) Compound (I-1):

Was synthesized according to the method described in Patent Document 3 (Japanese Unexamined Patent Publication No. 2016-155781), and the measurement result of gel permeation chromatography of the precursor diheptyl ester was found to have a number average molecular weight M _n = 1.25 × 10. ^{4. The} dispersity M _w / M _n = 1.85 (in terms of polystyrene) was used. When the circular dichroism spectrum of compound (I-1) was measured, a compound having a Δε value of 395 nm, which indicates optical purity, in the range of 19 to 21 was used.
(2) Synthesis of compound (II-1-Y) Solutions A and ee in which _{compound (I-1) (3.2 mg, 12 μmol) was dissolved in THF / H 2 O = 4/1 (v / v).} Solution B, 4- (4,6-dimethoxy-1,3,5) in which 1-phenylethylamine (6.3 μL, 49 μmol _{) was dissolved in THF / H 2 O = 4/1 (v / v).} -Triazine-2-yl) -4-methylmorpholinium chloride (DMT-MM) (13.6 mg, 49 μmol _{) was dissolved in THF / H 2} O = 2/1 (v / v) to prepare a solution C. did. Solutions A, B and C were mixed in a reaction vial under room temperature conditions and stirred for 1 hour. After completion of the reaction, it was distilled off under reduced pressure to THF, of H _{2 O} remaining in the vial tubes were removed by freeze drying overnight. Then, THF (1.2 mL) was added to dissolve the produced polymer, and membrane filtration was performed to remove the precipitated DMT-MM. The obtained filtrate was added to the vial tubes in a fixed amount and vacuum dried to obtain 1 μmol of compound (II-1) in each vial tube. Further, using 1-phenylethylamines having different ees (S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R90, R92, R94, R96, R98, R100 (% ee)), By performing the same operation, compounds (II-1-Y) into which 1-phenylethylamine of different ees were introduced were obtained.

For other chiralamines (1-cyclohexylethylamine and alanine tert-butyl ester), compounds (II-2-Y) and compounds (II-3-Y) in which different ee chiralamines were introduced were synthesized by the same operation. ..

Example 2
Control of non-linear responsiveness of color tone and fluorescence intensity change in tetrahydrofuran (first solvent) / N, N-dimethylformamide (second solvent) system in compound (II-1-Y) Obtained in Example 1. Tetrahydrofuran (first solvent) / N, N of compound (II-1-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100 (% ee)). -Changes in absorption intensity due to differences in ee when the absorption spectrum of ^{a solution (polymer concentration: 1.0 x 10 -3} M) dissolved in a 90:10 mixed solvent of dimethylformamide (second solvent) was measured. Changes in the fluorescence spectrum when excited at 350 nm are shown in FIGS. 1a and 1b. Further, a plot of the change in absorption intensity at 540 nm of the absorption spectrum when the mixed solvent ratio was changed to 100: 0, 90:10 and 85:15 was plotted in FIG. 2a, and the maximum value of the fluorescence intensity was plotted. Is shown in b. From these results, the non-linear response of 1-phenylethylamine, which is an aliphatic primary amine containing an aromatic ring, to the enantiomeric excess regulates the mixing ratio of tetrahydrofuran and dimethylformamide in both the absorption spectrum and the fluorescence spectrum. It turned out that it is possible to change it. Further, as shown in FIGS. 3A to 3F, it was found that the change in the color of the solution in the region where these non-linear responsiveness is large can be easily recognized visually.

Example 3
Control of non-linear responsiveness of color change in tetrachloroethane (first solvent) / acetone (second solvent) system in compound (II-1-Y) Compound (II-1-Y) obtained in Example 1 ) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100), tetrachloroethane (first solvent) / acetone (second solvent) 100: 0, and FIG. 4 shows a plot of the change in absorption intensity at 520 nm when the absorption spectrum of each solution (polymer concentration: 1.0 × 10 ^{-3 M) dissolved in a mixed solvent of 80:20 was measured.} From these results, it was found that the non-linear response of 1-phenylethylamine to the enantiomeric excess can be similarly controlled by the combination with the second solvent even when the first solvent is changed from tetrahydrofuran to tetrachloroethane. ..

Example 4
Control of non-linear responsiveness of color change in tetrahydrofuran (first solvent) / acetone (second solvent) system in compound (II-1-Y) Compound (II-1-Y) obtained in Example 1 (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) is mixed with tetrahydrofuran (first solvent) / acetone (second solvent) at 100: 0, 80:20. , 60:40 and 40:60 mixed solvent dissolved in each solution (polymer concentration: 1.0 × 10 ^-3 M), plotting the change in absorption intensity at 540 nm when measuring the absorption spectrum. Shown in 5. From these results, the non-linear response of 1-phenylethylamine to the enantiomeric excess can be similarly controlled by the combination with the first solvent even when the second solvent is changed from N, N-dimethylformamide to acetone. It turned out.

Example 5
Colorimetric Discrimination of Mirror Excess Rate in High Optical Purity Region of Compound (II-1-Y) Compound (II-1-Y) (Y = R90, R92, R94, R96, R98, ^{Absorption of each solution (polymer concentration: 1.0 × 10 -3} M) (standard sample) in which R100) was dissolved in a 30:70 mixed solvent of tetrahydrofuran (first solvent) / acetone (second solvent). FIG. 6 shows the change in absorption intensity due to the difference in the excess ratio of the mirror image when the spectrum was measured. According to the results of FIG. 6, the difference in the enantiomeric excess in the high optical purity region (90 to 100% ee) of 1-phenylethylamine can also be identified by appropriately selecting the first solvent and the second solvent. It became clear that it was possible. Further, as shown in FIG. 7, it was found that the change in the solution color for each 2% ee can be easily recognized visually. Further, as shown in FIG. 8, even for a slight change in color tone that is difficult for the human eye to recognize, an image was taken using the camera function of a commercially available iPhone 6S manufactured by Apple Inc., and the obtained image was obtained. An RGB plot (Fig. 8) of the standard sample was created by dividing into three components, Red (R), Green (G), and Blue (B), by RGB analysis processing using the image analysis application Pixel Picker built into the iPhone. In particular, since the intensities of the R and G components changed significantly even in the high optical purity region, the difference in the mirror image excess rate even when based on the change in color tone that is difficult to visually identify by using a smartphone or the like. It was confirmed that it is possible to identify.
The chirality and optical purity of 1-phenylethylamine whose optical purity is unknown can be accurately determined by comparative observation with the standard sample as described above or the calibration curve prepared by the RGB analysis process.

Example 6
Control of non-linear responsiveness of color change in tetrahydrofuran (first solvent) / acetone (second solvent) system in compound (II-2-Y) Compound (II-2-Y) obtained in Example 1 (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) is mixed with chloroform (first solvent) / acetone (second solvent) at 100: 0 and 95: 5. FIG. 9 shows a plot of the change in absorption intensity at 520 nm when the absorption spectrum of each solution (standard sample) (polymer concentration: 1.0 × 10 ^{-3 M) dissolved in the mixed solvent of (1) was measured.} .. According to the results of FIG. 9, the non-linear response to the enantiomeric excess of 1-cyclohexylethylamine, which is an aliphatic primary amine containing no aromatic ring, is the same as that of 1-phenylethylamine with the first solvent. It was found that the control was possible by adjusting the mixing ratio of the second solvent.
From this result, as in the case of 1-phenylethylamine, the chirality and optical purity of 1-cyclohexylethylamine whose optical purity is unknown can be accurately determined.

Example 7
Control of non-linear responsiveness of color change in tetrahydrofuran (first solvent) / N, N-dimethylformamide (second solvent) system in compound (II-3-Y) The compound (II) obtained in Example 1. -3-Y) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100), tetrahydrofuran (first solvent) / N, N-dimethylformamide (second) Change in absorption intensity at 560 nm when the absorption spectrum of ^{each solution (standard sample) (polymer concentration: 1.0 × 10 -3} M) dissolved in a mixed solvent of 100: 0 and 90:10 of the solvent) was measured. Is shown in FIG. According to the results of FIG. 10, the non-linear response of the amino acid derivative alanine tert-butyl ester to the enantiomeric excess adjusts the mixing ratio of the first solvent and the second solvent as in the case of 1-phenylethylamine. By doing so, it was found that it was controllable.
From this result, as in the case of 1-phenylethylamine, the chirality and optical purity of alanine tert-butyl ester whose optical purity is unknown can be accurately determined.

Example 8
Control of non-linear responsiveness of color change in tetrahydrofuran (first solvent) / dimethyl sulfoxide (second solvent) system in compound (II-1-Y) The compound (II-1-Y) obtained in Example 1 ) (Y = S100, S80, S60, S40, S20, S0, R20, R40, R60, R80, R100) and tetrahydrofuran (first solvent) / dimethyl sulfoxide (second solvent) 100: 0, 96. .Plot of the change in absorption intensity at 550 nm when the absorption spectrum of ^{each solution (polymer concentration: 1.0 × 10 -3} M) dissolved in a mixed solvent of 5: 3.5 and 95: 5 was measured. Is shown in FIG. According to the results of FIG. 11, the non-linear response of phenylethylamine to the enantiomeric excess was determined by using the second solvent as N, N-dimethylformamide (38.3) or acetone (21. When dimethyl sulfoxide (46.7) having a relative permittivity larger than 40 is replaced from 4), unlike the cases of Examples 2 to 4, the non-linear responsiveness is caused by a slight change in the amount of the second solvent added. It was confirmed that the optical purity region (region that can be measured with high accuracy) that shows the above shifts significantly. Therefore, when a solvent having a relative permittivity of more than 40 is used as the second solvent, the influence of the measurement error based on the weighing error of the second solvent cannot be ignored, and therefore the non-linear response with high accuracy cannot be ignored. It turns out that it can be difficult to control.

The above results are obtained by photographing the chirality and optical purity of optically active chiralamine, which is usually difficult to accurately identify chirality and determine optical purity without using expensive and special analytical instruments, with a commercially available digital camera or smartphone. It shows that it is possible to easily and accurately identify and determine by a photographic image or by visual inspection.

The compound (II) obtained by condensing an optically active chiralamine compound and the compound (I) to amidate the compound (II), which is an organic solvent having a specific dielectric constant of less than 10, and a specific solvent having a specific dielectric constant of 15 or more and 40 or less. The solution prepared by dissolving in a mixed solvent consisting of a second solvent, which is an organic solvent, has a region having a large non-linear response in its color tone and fluorescence as an optical purity region depending on the mixing ratio of the first solvent and the second solvent. Since it can be freely shifted, the demand is high, but even in the high optical purity region (90 to 100% ee) where it has been difficult to determine the optical purity visually or by the fluorescence spectrum, the optical activity is extremely high. It is possible to determine the chirality and optical purity of the chiralamine compound. Further, according to the present invention, the chirality and optical purity of various kinds of optically active chiralamine compounds can be analyzed after taking a picture with an inexpensive camera or smartphone without using an expensive and special measuring device (RGB). It is possible to accurately identify and determine the difference in the excess ratio of enantiomers simply by comparing and observing the color tone of a standard sample solution with known optical purity by means of a calibration curve (calibration curve created by analysis) or by visual inspection. It is possible to provide a practical chirality sensing method.

Claims (5)

Equation (I) with a unidirectionally wound helical structure:

[During the ceremony,
^{R 1, R 1 ', R} 2, R 2', R 3, R 3 'R 4 and ^{R 4'} are each a hydrogen atom independently, a halogen atom, an optionally substituted alkyl group, substituted Indicates a cycloalkyl group which may be substituted, an alkoxy group which may be substituted, an alkylthio group which may be substituted, a tri-substituted silyl group, a tri-substituted syroxy group or an acyloxy group which may be substituted; Indicates an integer of 10 or more. ]
A step of condensing a poly (diphenylacetylene) compound represented by (diphenylacetylene) or a salt thereof and two or more known optically active chiralamine compounds having different optical purity to obtain two or more amidated compounds.
The amidated two or more kinds of compounds are mixed into a mixed solvent consisting of a first solvent which is an organic solvent having a specific dielectric constant of less than 10 and a second solvent which is an organic solvent having a specific dielectric constant of 15 or more and 40 or less. In the step of preparing each dissolved solution as a standard sample, a compound amidated by condensing the compound of the above formula (I) or a salt thereof with an optically active chiralamine compound of an unknown subject whose kirarity and optical purity are unknown. By observing the color tone and / or fluorescence intensity of the solution of the amidated compound in comparison with the standard sample, the step of preparing the solution dissolved in the mixed solvent, and the optically active chiralamine compound of the test subject. A method for determining the kirarity and optical purity of an optically active chiralamine compound, which comprises a step of determining the kirarity and optical purity of the optically active chiralamine compound. The method according to claim 1, wherein the mixed solvent of the solution prepared as the standard sample is selected from two or more mixed solvents having different mixing ratios. The first solvent is chloroform, dichloromethane, 1,1,2,2-tetrachloroethane, tetrahydrofuran or 1,4-dioxane, and the second solvent is acetone, methylethylketone, N, N-dimethylformamide or N. , N-Dimethylacetamide, the method of claim 1 or 2. The method according to claim 1 or 2, wherein the first solvent is 1,1,2,2-tetrachloroethane or tetrahydrofuran, and the second solvent is acetone or N, N-dimethylformamide. The method according to any one of claims 1 to 4, wherein changes in the color tone and / or fluorescence intensity of the solution are comparatively observed visually or by photographic images.

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