JP2017083172A - Method for making sample for crystal structure analysis and monocular structure deciding method of organic compound having functional group - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for making a useful sample for crystal structure analysis when deciding monocular structure of an organic compound having a functional group and a method for deciding the molecular structure of the organic compound having the functional group by using the sample for crystal structure analysis obtained by this method.SOLUTION: A method for making a sample for crystal structure analysis for deciding molecular structure of an organic compound having a functional group includes a step of making a sample for crystal structure analysis in which molecules of an organic compound are regularly arranged in a fine pore and/or a hollow of a single crystal being a porous compound, by making the single crystal come into contact with solvent solution containing the organic compound, the single crystal having a three-dimensional skeleton constituted of one or two or more molecular chains or one or two or more molecular chains and a skeleton formative compound, and the fine pore and/or the hollow partitioned and formed by the three-dimensional skeleton and three-dimensionally regularly arranged, in which the three-dimensional skeleton has the functional group interacting with the functional group in the fine pore and/or the hollow.SELECTED DRAWING: Figure 5

Description

  The present invention relates to a method for preparing a crystal structure analysis sample useful for determining the molecular structure of an organic compound having a functional group, and a functional group having a functional group using the crystal structure analysis sample obtained by this method. The present invention relates to a method for determining the molecular structure of an organic compound.

In recent years, it has become very important to identify compounds having functional groups such as metabolites. For example, in the development of pharmaceuticals, in order to ensure the effectiveness and safety of pharmaceuticals, identification of metabolites of drug active ingredients (determination of molecular structure) is required in cell experiments, tissue experiments, animal experiments, clinical studies, etc. Has been done.
However, since the amount of metabolites collected from a living body is usually a very small amount, a sample such as LC-MS (liquid chromatography-mass spectrometry) or NMR (nuclear magnetic resonance method) is used to identify the metabolite. Even so, analysis methods capable of analysis have been mainly used. For example, Patent Document 1 discloses a method for analyzing a drug metabolite, which combines RI (radioisotope) quantitative analysis and mass spectrometry.

On the other hand, an X-ray crystal structure analysis method is known as a method for determining the molecular structure of an organic compound. The X-ray crystal structure analysis method is an extremely useful method because a molecular structure of an organic compound can be accurately determined if a high-quality single crystal can be produced.
However, when trying to produce a single crystal by a conventional method, it is necessary to repeat a number of trial and error experiments until finding the optimum conditions for crystallization. It was necessary to secure a sample of several milligrams.

Therefore, when the molecular structure of trace substances such as drug metabolites is determined by X-ray crystal structure analysis, repeated kinetic experiments or separate chemical synthesis may be performed in order to secure a sample of several milligrams. Enormous amounts of time and money are spent.
For these reasons, there have been few reports on the molecular structure of metabolites that can be obtained only in trace amounts by X-ray crystal structure analysis.

  Therefore, the technique for efficiently determining the molecular structure of organic compounds by X-ray crystal structure analysis is not limited to determining the molecular structure of metabolites, but identifies trace amounts of impurities contained in agricultural drugs and their raw materials. It is also extremely important when developing safer agricultural pharmaceuticals, and when identifying minute amounts of impurities contained in raw materials used in the production of electronic components to produce higher performance electronic components.

  In connection with the present invention, the present inventors have described the fine structure of a single crystal of a porous compound having a three-dimensional skeleton and three-dimensionally ordered pores formed by partitioning the three-dimensional skeleton. By conducting X-ray crystal structure analysis of a single crystal of an inclusion body obtained by including triphenylene as a guest molecule in a pore, the state of the triphenylene molecule in the pore can be known by an X-ray crystal structure analysis method. This is reported (Non-Patent Document 1).

WO2010 / 041459 pamphlet

J.Am.Chem.Soc. 2004,126,16292-16293

From the experimental results described in Non-Patent Document 1, the X-ray crystal structure analysis is performed using the measurement sample obtained by aligning the organic compound molecules in the pores of the single crystal. It is thought that the structure can be determined efficiently.
However, depending on the organic compound, it may be difficult to obtain a high-quality measurement sample, or it may take a long time to prepare the measurement sample.

  The present invention has been made in view of such circumstances, and a method for efficiently producing a crystal structure analysis sample useful in determining the molecular structure of an organic compound, and the crystal structure analysis obtained by this method It is an object of the present invention to provide a method for determining the molecular structure of an organic compound using a sample for use.

  The present inventors diligently studied to solve the above problems. As a result, many metabolites and the like have functional groups, and organic compounds having such functional groups (hereinafter sometimes referred to as “functional groups (a)”) (hereinafter “organic compounds (A)”). A porous compound having a functional group that interacts with the functional group (a) (hereinafter also referred to as “functional group (b)”) in the pores and / or hollows. It has been found that the target crystal structure analysis sample can be efficiently produced by bringing the crystal into contact with a solvent solution containing the organic compound (A), and the present invention has been completed.

  Thus, according to the present invention, there are provided the following (1) to (10) method for preparing a crystal structure analysis sample and (11) the method for determining the molecular structure of an organic compound having a functional group.

(1) A method for preparing a crystal structure analysis sample for determining the molecular structure of an organic compound (A) having a functional group (a), comprising one or more molecular chains, or one or two or more molecular chains A three-dimensional skeleton composed of a molecular chain and a skeleton-forming compound, and three-dimensionally regularly arranged pores and / or hollows formed by being partitioned by the three-dimensional skeleton. A single crystal of a porous compound having a skeleton having a functional group (b) interacting with the functional group (a) in the pores and / or hollows is contacted with a solvent solution containing the organic compound (A). A step of preparing a crystal structure analysis sample in which the molecules of the organic compound (A) are regularly arranged in the pores and / or hollows of the single crystal. A method for preparing a sample for crystal structure analysis.
(2) The interaction between the functional group (a) and the functional group (b) is an electrostatic interaction, a hydrogen bond, a hydrophobic interaction, a π-π interaction, or a CH-π interaction. ) For preparing a crystal structure analysis sample.
(3) The functional group (a) is a group having at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom, an alkyl group optionally having a halogen atom, a halogen atom The method for producing a sample for crystal structure analysis according to (1) or (2), which is an aryl group which may have a hydrogen atom or a group containing a metal ion.
(4) The functional group (b) is a group having at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom, an alkyl group optionally having a halogen atom, a halogen atom The method for producing a sample for crystal structure analysis according to any one of (1) to (3), which is an aryl group which may have a group or a group containing a metal ion.
(5) Preparation of the sample for crystal structure analysis in any one of (1)-(4) whose content of the organic compound (A) in the solvent solution containing the said organic compound (A) is 5 mg or less Method.
(6) The crystal according to any one of (1) to (5), wherein the porous compound is a polynuclear metal complex containing a ligand having two or more coordination sites and a metal ion as a central metal. A method for preparing a sample for structural analysis.
(7) The porous compound is a polynuclear metal complex including a ligand having two or more coordination sites, a metal ion as a central metal, and a skeleton-forming aromatic compound having a functional group (b). A method for producing a crystal structure analysis sample according to any one of (1) to (6).
(8) The ligand having two or more coordination sites is represented by the following formula (1)

(In the formula, Ar represents a trivalent aromatic group which may have a substituent. X ^{1 to} X ³ are each independently a divalent organic group, or Ar and Y ¹ to Y ^3. (Y ¹ to Y ³ each independently represents a monovalent organic group having a coordination site.)
The method for producing a crystal structure analysis sample according to (6) or (7), which is a tridentate ligand represented by
(9) The crystal structure analysis sample according to any one of (6) to (8), wherein the metal ion as the central metal is a metal ion of Group 8 to 12 of the periodic table Manufacturing method.
(10) The means for bringing the single crystal into contact with the solvent solution containing the organic compound (A) immerses the single crystal in the solvent solution containing the organic compound (A). (9) The method for producing a sample for crystal structure analysis according to any one of (9).
(11) A method for determining the molecular structure of an organic compound having a functional group, wherein the crystal structure analysis sample obtained by the method according to any one of (1) to (10) is used. And determining the molecular structure of the organic compound (A) having the functional group (a), and determining the molecular structure of the organic compound having the functional group.

  According to the present invention, a method for efficiently producing a crystal structure analysis sample useful for determining the molecular structure of an organic compound (A) having a functional group (a), and the crystal structure obtained by this method A method for determining the molecular structure of an organic compound (A) having a functional group (a) using a sample for analysis is provided.

It is a figure showing the direction where the pore of a single crystal extends. 1 is a diagram illustrating a three-dimensional skeleton of a polynuclear metal complex 1. FIG. 3 is a diagram illustrating a three-dimensional network structure of a polynuclear metal complex 3. FIG. 3 is a diagram illustrating a three-dimensional network structure of a polynuclear metal complex 5. FIG. 1 is a diagram illustrating a polynuclear metal complex obtained by inclusion of 4,4,4-trifluorobutyric acid obtained in Example 1. FIG. 3 is a diagram showing a polynuclear metal complex obtained by inclusion of cis-9-hexadecenoic acid obtained in Example 2. FIG. 4 is a diagram showing a polynuclear metal complex obtained by inclusion of petrothelic acid obtained in Example 3. FIG.

  Hereinafter, the present invention will be described in detail by dividing it into 1) a method for preparing a sample for crystal structure analysis, and 2) a method for determining the molecular structure of an organic compound having a functional group.

1) Method for preparing sample for crystal structure analysis The method for preparing a sample for crystal structure analysis of the present invention is as follows.
A method for preparing a crystal structure analysis sample for determining a molecular structure of an organic compound (A) having a functional group (a),
Three-dimensional skeleton composed of one or two or more molecular chains, or one or two or more molecular chains and a skeleton-forming compound, and three-dimensionally regularly formed by being partitioned by the three-dimensional skeleton , Pores and / or hollows,
A single crystal of a porous compound in which the three-dimensional skeleton has a functional group (b) that interacts with the functional group (a) in the pores and / or hollows,
By contacting with a solvent solution containing the organic compound (A),
There is a step of producing a sample for crystal structure analysis in which the molecules of the organic compound (A) are regularly arranged in the pores and / or hollows of the single crystal.

(I) Organic compound (A) having functional group (a)
The organic compound (A) is a compound having a functional group (a), and its molecular structure is determined by a crystal structure analysis method using a crystal structure analysis sample obtained by the method of the present invention. .

  In general, when an organic compound is classified into several groups according to its property (reactivity), the functional group is an atomic group that causes a common reactivity exhibited by compounds belonging to the same group, or a bonding mode. Say. Examples include hydroxyl groups (—OH) of alcohols, carbonyl groups (> C═O) of ketones, carboxyl groups (—COOH) of carboxylic acids, amides (—C (═O) —NH—), and the like. However, it is not limited to these.

  In the present invention, the functional group (a) is not particularly limited as long as it is a functional group as defined above and can interact with the functional group (b). The interaction between the functional group (a) and the functional group (b) includes electrostatic interaction (Coulomb interaction, ion-dipole interaction, dipole interaction), hydrogen bond, hydrophobic interaction, π- Examples include π interaction, CH-π interaction, and coordination bond.

  As the functional group (a), a group having at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom (hereinafter sometimes referred to as a functional group (a-1)), a halogen atom May have an alkyl group [hereinafter sometimes referred to as a functional group (a-2)], an aryl group optionally having a halogen atom [hereinafter sometimes referred to as a functional group (a-3). ], Groups containing metal ions [hereinafter sometimes referred to as functional group (a-4)], and the like.

The functional group (a-1) is a group having at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom, and a phosphorus atom.
As the functional group (a-1), —CN, —N (R ¹ ) (R ² ), —OR ³ , —C (═O) R ⁴ , —C (═O) OR ⁵ , —O—C ^{(= O) R 6, -SR} 7, -C (= S) R 8, -C (= S) SR 9, -P (R 10) (R 11) of the ^{(R 12)} or the like, nitrogen atom, oxygen A monovalent group having one atom selected from the group consisting of an atom, a sulfur atom and a phosphorus atom;
_{^{-NO 2, -S (= O)}} R 13, -SO 2 R 14, -SO 3 R 15, -OP (= O) (OR 16) (OR 17), - O-P (= S) (OR ¹⁸ ) a monovalent group having two or more atoms selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom, such as (OR ¹⁹ );
^{-N = C (R 20) -} ,> C = N (R 21), - O -, - A- (OA) n -, - C (= O) -, - C (= O) -O-, A divalent group having one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom, such as -S-;
A nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom, such as —N (R ²² ) —C (═O) —, —N (R ²³ ) —C (═S) —, —SO—, —SO ₂ —; A divalent group having two or more atoms selected from the group consisting of:
A group formed by combining these groups; and the like.
In said formula, R < ¹ > -R < ²³ > represents the C1-C20 hydrocarbon group which may have a hydrogen atom or a halogen atom each independently.
Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. A represents a C1-C10 alkylene group, such as a methylene group, an ethylene group, a trimethylene group, and a propylene group.
n represents an integer of 1 to 20.

When the functional group (a-1) is an acidic group (a group that can be deprotonated), the functional group (a-1) may be an electrically neutral group or a deprotonated anion. It may be in a state. In addition, when the functional group (a-1) is a basic group (a group that can be protonated), the functional group (a-1) may be electrically neutral or in a protonated cationic state. It may be.
When the functional group (a) is the functional group (a-1), the functional group (a) can interact with the functional group (b) mainly by electrostatic interaction or hydrogen bonding.

The functional group (a-2) is an alkyl group that may have a halogen atom.
As the alkyl group of the functional group (a-2), linear or branched such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group and t-butyl group A chain alkyl group. Examples of the halogen atom of the functional group (a-2) include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
1-20 are preferable, as for carbon number of a functional group (a-2), 2-15 are more preferable, and 3-10 are more preferable.
When the functional group (a) is the functional group (a-2), the functional group (a) is mainly formed by hydrophobic interaction, ion-dipole interaction, dipole interaction, hydrogen bond, It can interact with the functional group (b).

The functional group (a-3) is an aryl group that may have a halogen atom.
Examples of the aryl group of the functional group (a-3) include a phenyl group, a 1-naphthyl group, and a 2-naphthyl group.
Examples of the halogen atom that the aryl group has include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
When the functional group (a) is the functional group (a-3), the functional group (a) interacts with the functional group (b) mainly by π-π interaction and CH-π interaction. be able to.

The functional group (a-4) is a group containing a metal ion.
Examples of the group containing a metal ion of the functional group (a-4) include an atomic group containing a metal ion in a mononuclear complex, an atomic group containing a metal ion in a polynuclear complex, and the like.
Examples of metal ions of mononuclear complexes and polynuclear complexes include alkali metal ions such as lithium ions and sodium ions; beryllium ions; magnesium ions; alkaline earth metal ions such as calcium ions and strontium ions; chromium ions, manganese ions, and iron ions Transition metal ions such as aluminum ions, zinc ions of typical elements such as zinc ions, and the like.
When the functional group (a) is the functional group (a-4), the functional group (a) can interact with the functional group (b) mainly by electrostatic interaction or coordination bond. .

  The organic compound (A) may have one functional group (a) or a plurality of functional groups (a) in the molecule, and the bonding site of the functional group (a) is not particularly limited.

The size of the organic compound (A) is not particularly limited as long as the organic compound (A) has a size capable of entering the pores and / or hollows of the single crystal. The molecular weight of the organic compound (A) is usually 20 to 3,000, preferably 100 to 2,000.
In the present invention, the molecular size of the organic compound (A) is grasped to some extent by nuclear magnetic resonance spectroscopy, mass spectrometry, elemental analysis, etc., and a single crystal having appropriate pores and hollows is appropriately selected in advance. It is also preferable to use them.

  Among these, as the organic compound (A), carboxylic acids are preferable because they are important as active ingredients of agricultural drugs, metabolites thereof, and the like. 1-40 are preferable and, as for carbon number of carboxylic acids, 4-35 are more preferable.

(Ii) Solvent solution containing organic compound (A) The solvent of the solvent solution containing organic compound (A) is not particularly limited as long as it does not dissolve the single crystal used and dissolves organic compound (A). It is not limited.
As will be described later, when the operation of concentrating the solvent solution containing the organic compound (A) by volatilizing the solvent from the solvent solution containing the organic compound (A), the solvent used is normal pressure (1 × The boiling point at 10 ⁵ Pa) is preferably 200 ° C. or less, more preferably −50 to 185 ° C., and further preferably 30 to 80 ° C.

  Specific examples of the solvent used include aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, 1,2-dichlorobenzene and nitrobenzene; fats such as n-butane, n-pentane, n-hexane and n-heptane. Aromatic hydrocarbons such as cyclopentane, cyclohexane and cycloheptane; Nitriles such as acetonitrile and benzonitrile; Sulfoxides such as dimethyl sulfoxide (DMSO); N, N-dimethylformamide and N-methyl Amides such as pyrrolidone; Ethers such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane and 1,4-dioxane; Alcohols such as methanol, ethanol and isopropyl alcohol; Ketones such as acetone, methyl ethyl ketone and cyclohexanone; Cellosolves such as cellosolve; Halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride and 1,2-dichloroethane; Esters such as methyl acetate, ethyl acetate, ethyl lactate and ethyl propionate; Water; . These solvents can be used alone or in combination of two or more.

The content of the organic compound (A) in the solvent solution containing the organic compound (A) is not particularly limited. For example, 5 mg or less, preferably 0.5 μg or more and 5 mg or less, more preferably 0.5 μg or more and 1 mg or less, and further preferably 1 μg or more and 0.5 mg or less.
In the conventional crystallization method, when examining crystallization conditions for obtaining a single crystal of a compound, a sample of at least about 5 mg is required. According to the method of the present invention, even if the content of the organic compound (A) is 5 mg or less, a target crystal structure analysis sample can be efficiently produced.

  The concentration of the organic compound (A) in the solvent solution containing the organic compound (A) is not particularly limited, but is usually 0.001 to 50 μg / μL from the viewpoint of efficiently producing a high-quality crystal structure analysis sample. Preferably it is 0.01-5 microgram / microliter, More preferably, it is 0.1-1 microgram / microliter.

  The solvent solution containing the organic compound (A) may be subjected to a purification treatment by a known purification method before use in the present invention. Examples of the purification method include purification methods such as centrifugation, filtration, dialysis, solvent extraction, electrophoresis, and liquid chromatography. These purification methods can be used singly or in combination of two or more.

(Iii) Single crystal of porous compound The single crystal of the porous compound used in the present invention is a three-dimensional skeleton composed of one or more molecular chains, or one or two or more molecular chains and a skeleton-forming compound. And three-dimensionally regularly arranged pores and / or cavities formed by being partitioned by the three-dimensional skeleton, wherein the three-dimensional skeleton interacts with the functional group (a). The group (b) is present in the pores and / or hollows.

The three-dimensional skeleton refers to a skeleton-like structure having a three-dimensional extension inside a single crystal. The three-dimensional skeleton is composed of one or more molecular chains, or one or two or more molecular chains and a skeleton-forming compound.
“Molecular chain” refers to an organization organized by covalent bonds and / or coordinate bonds. This molecular chain may have a branched structure or a cyclic structure.
Examples of the three-dimensional skeleton composed of one molecular chain include a skeleton organized in a “jungle gym” shape.
As a three-dimensional skeleton composed of two or more molecular chains, two or more molecular chains are organized as a whole by interactions such as hydrogen bonds, π-π stacking interactions, van der Waals forces, etc. Refers to the skeleton. For example, there is a skeleton in which two molecular chains are entangled in a “Chienowa” shape. Examples of such a three-dimensional skeleton include the three-dimensional skeletons of polynuclear metal complexes 1 and 2 described later.

“Skeletogenic compounds” do not form part of a molecular chain, but form part of a three-dimensional skeleton by interactions such as hydrogen bonding, π-π stacking interaction, van der Waals force, etc. Refers to the compound. For example, the skeleton-forming aromatic compound in the polynuclear metal complex mentioned later is mentioned.
“Three-dimensionally ordered pores and / or hollows” means pores and hollows that are regularly aligned without being disturbed to the extent that pores and hollows can be confirmed by crystal structure analysis. Say.
“Pore” and “hollow” represent an internal space in the single crystal. The internal space extending in a cylindrical shape is called “pore”, and the other internal space is called “hollow”.

  The size of the pore is defined as an inscribed circle of the pore (hereinafter simply referred to as a parallel plane) parallel to the crystal plane that is closest to the perpendicular to the direction in which the pore extends (hereinafter simply referred to as a parallel plane). There is a correlation with the diameter of “the inscribed circle of the pore”. The larger the inscribed circle, the larger the pore, and the smaller the inscribed circle, the smaller the pore.

The “direction in which the pores extend” can be determined by the following method.
That is, first, a crystal plane X (A plane, B plane, C plane, or a diagonal plane of each) in an appropriate direction across the target pore is selected. Then, by expressing the atoms that exist on the crystal plane X and constitute the three-dimensional skeleton using the van der Waals radii, a cross-sectional view of the pore having the crystal plane X as a cutting plane is drawn. Similarly, a cross-sectional view of a pore having a crystal plane Y shifted from the crystal plane X by one unit cell as a cut plane is drawn. Next, the centers of the cross-sectional shapes of the pores in the respective crystal planes are connected with a straight line (dashed line) in the three-dimensional view (see FIG. 1). The direction of the straight line obtained at this time is the direction in which the pores extend.

The “diameter of the inscribed circle of the pore” can be obtained by the following method.
That is, first, a cross-sectional view of the pore having the parallel plane as a cut plane is drawn by the same method as described above. Next, after drawing the inscribed circle of the pore in the cross-sectional view and measuring the diameter, the obtained measured value is converted into an actual scale to obtain the diameter of the inscribed circle of the actual pore. be able to.
Furthermore, by measuring the diameter of the inscribed circle of the pore in each parallel surface while gradually translating the parallel surface by one unit cell, the diameter of the inscribed circle of the narrowest part and the widest The diameter of the inscribed circle of the part is obtained.

  The diameter of the inscribed circle of the single crystal pores used in the present invention is preferably 2 to 30 mm, and more preferably 3 to 10 mm.

When the shape of the pore is significantly different from a perfect circle, it is preferable to predict the inclusion ability of the single crystal from the minor axis and major axis of the inscribed ellipse of the pore in the parallel plane.
The major axis of the inscribed ellipse of the single crystal pores used in the present invention is preferably 2 to 30 mm, and more preferably 3 to 10 mm. Further, the minor axis of the inscribed ellipse of the single crystal pores is preferably 2 to 30 mm, and more preferably 3 to 10 mm.

The pore volume of the single crystal used in the present invention is described in the paper (A): Acta Crystallogr. A 46, 194-201 (1990). That is, it is possible to calculate using “volume of single crystal × porosity in unit cell” based on Solvent Accessible Void (void volume in a unit cell) calculated by a calculation program (PLATON SQUEEZE PROGRAM).
Single crystals of pore volume used in the present invention (all pore volume in the grain of the single crystal) is preferably ^{1 × 10 -7 ~0.1mm 3, 1} × 10 -5 ~1 × 10 - ³ mm ³ is more preferable.

  Further, when the single crystal has a hollow, the size of the hollow can also be obtained by the method described in the paper (A), similarly to the pore volume.

  The single crystal used in the present invention preferably has a cubic or cuboid shape. The one side is preferably 10 to 1000 μm, more preferably 60 to 200 μm. By using a single crystal having such a shape and size, a good quality crystal structure analysis sample can be easily obtained.

  The single crystal to be used is irradiated with MoKα rays (wavelength: 0.71 Å) generated at a tube voltage of 24 kV and a tube current of 50 mA, and when diffracted X-rays are detected by a CCD detector, at least 1.5 Å. Those that can determine the molecular structure with a resolution of 1 are preferred. By using a single crystal having such characteristics, a sample for crystal structure analysis of good quality can be easily obtained.

The three-dimensional skeleton has a functional group (b) that can interact with the functional group (a).
As the functional group (b), a group having at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom (hereinafter sometimes referred to as a functional group (b-1)), a halogen atom May have an alkyl group [hereinafter sometimes referred to as a functional group (b-2)], an aryl group optionally having a halogen atom [hereinafter sometimes referred to as a functional group (b-3). ], A group containing a metal ion [hereinafter sometimes referred to as a functional group (b-4)], and the like.

  Specific examples of the functional groups (b-1), (b-2), (b-3), and (b-4) are the functional groups (a-1), (a-2), and (a- The same thing as what was shown as 3) and (a-4) is mentioned.

The size of the functional group (b) is not particularly limited as long as it does not block pores and / or hollows.
Carbon number of a functional group (b) becomes like this. Preferably it is 1-100, More preferably, it is 2-60, More preferably, it is 3-20.

In the method of the present invention, a crystal structure analysis can be efficiently performed by appropriately selecting a single crystal of a porous compound having an appropriate functional group (b) in accordance with the functional group (a) of the organic compound (A). Sample can be prepared.
For example, as shown in the following table, when the organic compound (A) is a carboxylic acid, a single crystal of a porous compound in which the functional group (b) is an amino group [—N (R ¹ ) (R ² )] is used. Thus, it is preferable to prepare a crystal structure analysis sample.
In addition, the combination of an organic compound (A) and a functional group (b) is not limited to the thing of the following table | surface. In the present invention, well-known techniques relating to intermolecular interactions can be used as appropriate.

In the table, R ¹ , R ² , R ²² , A, and n each have the same meaning as described above. Examples of the cationic group include-[N (R ¹ ) (R ² ) H] ⁺ .

Among these, the organic compound (A) is a carboxylic acid, and the functional group (b) is preferably a combination of amino groups [—N (R ¹ ) (R ² )]. Since the functional group (b) is an amino group, carboxylic acids important as active ingredients and metabolites of agricultural pharmaceuticals are efficiently incorporated into the pores and / or hollows of the single crystal of the porous compound, and the crystal structure An analysis sample can be obtained efficiently.

The single crystal of the porous compound used in the present invention has the three-dimensional skeleton and three-dimensionally regularly arranged pores and / or hollows that are partitioned by the three-dimensional skeleton. .
Examples of the single crystal of the porous compound include a single crystal of a polynuclear metal complex and a urea crystal. Among these, a single crystal of a polynuclear metal complex is preferable because the size of the pores and hollows and the position of the functional group (b) in the pores and hollows can be easily controlled.

The polynuclear metal complex includes a ligand having two or more coordination sites (hereinafter, sometimes referred to as “polydentate ligand”) and a metal ion as a central metal, in addition to these. Further, those containing a skeleton-forming aromatic compound can be mentioned. Among them, as described later, since a single crystal of a polynuclear metal complex rich in variations of the functional group (b) can be efficiently prepared, a polydentate ligand, a metal ion as a central metal, and a functional group ( Polynuclear metal complexes containing a skeleton-forming aromatic compound having b) are preferred.
In these polynuclear metal complexes, the functional group (b) can be introduced into the three-dimensional skeleton by using a polydentate ligand having a functional group (b) or a skeleton-forming aromatic compound.

The multidentate ligand is not particularly limited as long as it can form the three-dimensional skeleton, and a known multidentate ligand can be used.
Here, the “coordinating moiety” refers to an atom or atomic group in a ligand having an unshared electron pair capable of coordinating bond. Examples thereof include heteroatoms such as nitrogen atom, oxygen atom, sulfur atom and phosphorus atom; atomic groups such as nitro group, amino group, cyano group and carboxyl group; Especially, the atomic group containing a nitrogen atom or a nitrogen atom is preferable.
Especially, since the planarity of a ligand is high and a strong three-dimensional skeleton is easy to form, what has an aromatic ring as a polydentate ligand is preferable.
In general, when a multidentate ligand with a long distance from the center of the ligand to the coordination site is used, a single crystal of a polynuclear metal complex having relatively large pores and hollows is obtained. When a multidentate ligand having a short distance from the center of the child to the coordination site is used, a single crystal of a polynuclear metal complex having relatively small pores and hollows can be obtained.

  In addition, from the viewpoint of easily obtaining a single crystal having relatively large pores and hollows, the polydentate ligand is preferably a polydentate ligand having two or more coordination sites. More preferred is a ligand having three functional sites (hereinafter sometimes referred to as a “tridentate ligand”), and the unshared electron pairs (orbitals) of the three coordinating sites exist on a quasi-coplanar surface. In addition, it is more preferable that the three coordinating sites are arranged radially at equal intervals with respect to the center portion of the tridentate ligand.

Here, “existing on the quasi-coplanar plane” means that each unshared electron pair is on the same plane or is slightly displaced from the plane, for example, 20 ° or less with respect to the reference plane. It also includes the state that exists in a plane that intersects at.
In addition, “three coordinating sites are arranged radially at equal intervals with respect to the central portion of the tridentate ligand” means that on a line extending radially from the central portion of the ligand at equal intervals, It means a state in which three coordination sites are arranged at approximately the same distance from the central portion.

  As the tridentate ligand, for example, the following formula (1)

(In the formula, Ar represents a trivalent aromatic group which may have a substituent. X ^{1 to} X ³ are each independently a divalent organic group, or Ar and Y ¹ to Y ^3. And Y ¹ to Y ³ each independently represents a monovalent organic group having a coordination site.).

In formula (1), Ar represents a trivalent aromatic group.
The number of carbon atoms constituting Ar is usually 3 to 22, preferably 3 to 13, and more preferably 3 to 6.

  Ar is a trivalent aromatic group having a monocyclic structure composed of one 6-membered aromatic ring or a trivalent aromatic group having a condensed ring structure formed by condensing three 6-membered aromatic rings. Groups.

Examples of the trivalent aromatic group having a monocyclic structure composed of one 6-membered aromatic ring include groups represented by the following formulas (2a) to (2d). Examples of the trivalent aromatic group having a condensed ring structure formed by condensing three 6-membered aromatic rings include groups represented by the following formula (2e). In the formulas (2a) to (2e), “*” represents a bonding position with X ^{1 to} X ³ , respectively.

Among these, an aromatic group represented by the formula (2a) or (2b) is preferable, and an aromatic group represented by the formula (2b) is particularly preferable.
Ar may have a substituent at an arbitrary position of the aromatic group represented by formula (2a), formula (2c) to formula (2e). Such substituents include alkyl groups such as methyl, ethyl, isopropyl, n-propyl, and t-butyl; alkoxy groups such as methoxy, ethoxy, n-propoxy, and n-butoxy; fluorine A halogen atom such as an atom, a chlorine atom or a bromine atom; As this substituent, a group having a functional group (b) (hereinafter also referred to as “functional group (b) -containing group”) may be used.

X ^{1 to} X ³ each independently represent a divalent organic group or a single bond directly connecting Ar and Y ¹ to Y ³ .

As the divalent organic group, those capable of forming a π-electron conjugated system together with Ar are preferable. Since the divalent organic group represented by X ^{1 to} X ³ constitutes a π-electron conjugated system, the planarity of the tridentate ligand represented by the formula (1) is improved, and a stronger three-dimensional skeleton A structure is easily formed.
2-18 are preferable, as for the number of the carbon atoms which comprise a bivalent organic group, 2-12 are more preferable, and 2-6 are more preferable.

  Examples of the divalent organic group include a divalent unsaturated aliphatic group having 2 to 10 carbon atoms, a divalent organic group having a monocyclic structure composed of one 6-membered aromatic ring, and 2 to 4 6-membered aromatic rings. Divalent organic groups having a condensed ring structure formed by individual condensation, amide groups [—C (═O) —NH—], ester groups [—C (═O) —O—], and these divalent organic groups The combination of 2 or more types of group etc. are mentioned.

Examples of the divalent unsaturated aliphatic group having 2 to 10 carbon atoms include vinylene group and acetylene group (ethynylene group).
Examples of the divalent organic group having a monocyclic structure composed of one 6-membered aromatic ring include a 1,4-phenylene group.
Examples of the divalent organic group having a condensed ring structure obtained by condensing 2 to 4 6-membered aromatic rings include 1,4-naphthylene group and anthracene-1,4-diyl group.
Examples of combinations of two or more of these divalent organic groups include the following.

Among these, the following are preferable as the divalent organic group represented by X ^{1 to} X ³ .

The aromatic ring in the divalent organic group may contain a hetero atom such as a nitrogen atom, an oxygen atom, or a sulfur atom in the ring.
Further, the divalent organic group may have a substituent. Examples of the substituent include the same as those described above as the substituent for Ar.

Y ^{1 to} Y ³ each independently represents a monovalent organic group having a coordination site.
As the organic group represented by Y ^{1 to} Y ³ , those capable of forming a π-electron conjugated system together with Ar and X ^{1 to} X ³ are preferable.
When the organic group represented by Y ^{1 to} Y ³ constitutes a π-electron conjugated system, the planarity of the tridentate ligand represented by the formula (1) is improved, and a strong three-dimensional skeleton structure is formed. It becomes easy.
The number of carbon atoms that constitute the Y ¹ to Y ³ is preferably from 5 to 11, 5 to 7 is preferred.

Examples of Y ^{1 to} Y ³ include organic groups represented by the following formulas (3a) to (3f). In the equation (3a) ~ formula (3f), "*" ^represents a bonding position to X 1 to X ^3.

Among these, as Y ^{1 to} Y ³ , a group represented by the formula (3a) is particularly preferable.
Y ^{1 to} Y ³ may have a substituent at any position of the organic group represented by the formulas (3a) to (3f). Examples of the substituent include the same as those exemplified above as the substituent for Ar.

Tridentate in the ligand of formula ^{(1), Ar, X 1} ~X 3, Y 1 ~Y 3 by appropriately selecting the, to regulate pores and hollow size of the single crystal it can. By utilizing this method, a single crystal having pores and hollows of a size capable of including the target organic compound (A) can be efficiently obtained.

  As the tridentate ligand represented by the formula (1), since a strong three-dimensional skeleton structure is easily formed, the planarity and symmetry are high, and the π-conjugated system spreads throughout the ligand. Those are preferred. As such a tridentate ligand, a ligand represented by the following formulas (4a) to (4f) or a substituent (including a substituent (b)) at any position thereof. A ligand.

  Among these, as the tridentate ligand represented by the formula (1), 2,4,6-tris (4-pyridyl) -1,3,5-triazine (TPT) represented by the above formula (4a) is used. Is particularly preferred.

  Moreover, a commercial item can also be used as a polydentate ligand of a polynuclear metal complex. For example, the Sigma-Aldrich brochure published in September 2012 (Material Science Fundamentals No. 7-Porous Coordination Polymers (PCP) / Metal Organic Structures (MOF) Fundamentals) contains PCP / MOF coordination. As a compound for a child and a linker, pyrazine, 1,4-diazabicyclo [2.2.2] octane, 1,2-di (4-pyridyl) ethylene, 4,4′-bipyridyl, 4,4′-biphenyldicarboxylic acid , Benzene-1,3-dicarboxylic acid, pyrazine-2,3-dicarboxylic acid, pyrazine-3,5-dicarboxylic acid and the like. These ligands or a ligand having a substituent such as a functional group (b) -containing group at any position thereof can be used as the multidentate ligand of the polynuclear metal complex.

  The metal ion as the central metal of the polynuclear metal complex is not particularly limited as long as it can form a coordinate bond with the polydentate ligand to form a three-dimensional skeleton. Among them, ions of metals in Group 8 to 12 of the periodic table such as iron ions, cobalt ions, nickel ions, copper ions, zinc ions, silver ions, palladium ions, ruthenium ions, rhodium ions, and platinum ions are preferable. Of these, metal ions of groups 8 to 12 of the periodic table are more preferred. Among these, zinc (II) ions and cobalt (II) ions are particularly preferable because single crystals having large pores and hollows are easily obtained.

In addition to the polydentate ligand, a monodentate ligand may be coordinated with the central metal of the polynuclear metal complex. Such monodentate ligands include monovalent anions such as chloride ion (Cl ⁻ ), bromide ion (Br ⁻ ), iodide ion (I ⁻ ), thiocyanate ion (SCN ⁻ ); ammonia, monoalkyl Electrically neutral coordinating compounds such as amine, dialkylamine, trialkylamine, and ethylenediamine; and the like.

  The polynuclear metal complex is a reaction solvent (the solvent used for the synthesis of the polynuclear metal complex), a substitution solvent (refers to another solvent replaced with the reaction solvent, the same applies hereinafter), and a skeleton-forming aromatic described later. It may contain a compound.

“Skelet-forming aromatic compound” means an aromatic compound that interacts with a molecular chain constituting a three-dimensional skeleton (excluding covalent bonds and coordinate bonds) and can constitute a part of the three-dimensional skeleton. Say.
By including a skeleton-forming aromatic compound in the polynuclear metal complex, the three-dimensional skeleton is likely to become stronger, and the three-dimensional skeleton is further stabilized even after the molecules of the organic compound (A) are included. There is a case.

  Examples of the skeleton-forming aromatic compound include condensed polycyclic aromatic compounds. For example, what is shown by following formula (5a)-a formula (5i) is mentioned.

These condensed polycyclic aromatic compounds may have a substituent (including the substituent (b)) at an arbitrary position. Examples of the substituent include the same ones as those shown as the substituent of the multidentate ligand.
Especially, as a condensed polycyclic aromatic compound used for this invention, what has a functional group (b) is preferable. From the viewpoint of chemical synthesis, the functional group (b) rich in variations is more effective when the functional group (b) is introduced into the skeleton-forming aromatic compound than when the functional group (b) is introduced into the polydentate ligand. This is because there are many cases where it can be easily introduced.

  The skeleton-forming aromatic compound having a functional group (b) has a functional group (b) -containing group at any position of the skeleton-forming aromatic compound represented by the formulas (5a) to (5i). Is mentioned. Among them, a crystal structure analysis is performed using a single crystal of a porous compound containing triphenylene [compound represented by the above formula (5a)] as a skeleton-forming aromatic compound, and the state of the pores is sufficiently Since it has been clarified, a compound having a functional group (b) -containing group at the 1-position or 2-position of triphenylene is preferable, and a triphenylene compound having an amino group such as 1-aminotriphenylene or 2-aminotriphenylene is more preferable.

  Examples of the skeleton-forming aromatic compound having the functional group (b) and the polynuclear metal complex containing the skeleton-forming aromatic compound include WO 2007/102594, WO 2008/111665, JP 2010-18708, and JP The thing of 2010-184899 gazette is mentioned. In the present invention, the polynuclear metal complexes described in these documents can also be used.

Examples of the polynuclear metal complex include the following compounds.
(1) A compound comprising a ligand having a substituent (b) and a metal ion [polynuclear metal complex (α)]
(2) Compound [polynuclear metal complex (β)] comprising a skeleton-forming aromatic compound having a ligand, a metal ion, and a substituent (b)
(3) Compound [polynuclear metal complex (γ)] comprising a ligand having a substituent (b), a metal ion, and a skeleton-forming aromatic compound having a substituent (b)
(4) A compound in which a guest molecule such as a solvent molecule is included in the pore or hollow of any one of the polynuclear metal complexes (α) to (γ) [polynuclear metal complex (δ)]

  The polynuclear metal complex used in the present invention is preferably a polynuclear metal complex that does not lose crystallinity even after the organic compound (A) molecule is taken into the pores and hollows and has relatively large pores and hollows.

The polynuclear metal complex having such characteristics can be easily obtained by using a compound having the substituent (b) which is a tridentate ligand represented by the formula (1).
Specific examples include polynuclear metal complexes represented by the following formulas (6a) to (6c).

  In formulas (6a) to (6c), M represents a divalent metal ion belonging to Groups 8 to 12 of the periodic table, X represents a monovalent anionic monodentate ligand, and L represents The tridentate ligand represented by the formula (1) (or the tridentate ligand represented by the formula (1) and having a substituent (b)), and “solv” is a synthesis It represents a guest molecule such as a solvent molecule used sometimes, “SA” represents a skeleton-forming aromatic compound (or a skeleton-forming compound having a substituent (b)), and a, b, and c are arbitrary natural numbers. Represent. At least one of L and SA has a functional group (b).

  More specifically, the following polynuclear metal complexes are mentioned.

  In formulas (7a) to (7d), “solv”, “SA”, a, b, and c represent the same meaning as described above. However, one of TPT and SA has a functional group (b).

The three-dimensional skeleton of the polynuclear metal complex represented by the above formulas (6a) to (6c) can be estimated from the known three-dimensional skeleton of a polynuclear metal complex similar to these.
That is, although it is a polynuclear metal complex having no functional group (b), as L, the polynuclear metal complex using the TPT represented by the formula (4a) has previously incorporated guest molecules such as a solvent. The molecular structure is determined by single crystal X-ray structural analysis.
As long as the functional group (b) does not affect the three-dimensional skeleton of the polynuclear metal complex, the three-dimensional skeleton of the polynuclear metal complex used in the present invention is a polynuclear metal complex that does not have these functional groups (b). It is thought to be similar to a three-dimensional skeleton. Therefore, in the following, as T, the polynuclear metal complex [polynuclear metal complex represented by the following formulas (7a) to (7d)] having the functional group (b) using the TPT represented by the formula (4a). explain.
In the following, ligands and solvent molecules may be omitted as follows.

PhNO ₂ : Nitrobenzene TPH: Triphenylene PER: Perylene MeOH: Methanol DCB: 1,2-dichlorobenzene

(1) [(ZnI ₂ ) ₃ (TPT) ₂ (solv) _a ] _b (7a)
Examples of the polynuclear metal complex represented by the formula (7a) include Japanese Patent Application Laid-Open No. 2008-214584, J. MoI. Am. Chem. Soc. 2004, v. 126, pp 16292-16293 [(ZnI ₂ ) ₃ (TPT) ₂ (PhNO ₂ ) _5.5 ] _n (polynuclear metal complex 1) and all or part of the reaction solvent molecules in the polynuclear metal complex 1 The thing replaced with the substitution solvent is mentioned.

The three-dimensional skeleton of the polynuclear metal complex 1 is shown in FIGS.
The three-dimensional skeleton of the polynuclear metal complex 1 is composed of two molecular chains 1a and 1b. In the molecular chains 1a and 1b, each zinc (II) ion is coordinated in a tetracoordinate tetrahedral form by two TPT pyridyl groups and two iodide ions. The structures containing the zinc (II) ions are three-dimensionally connected by TPT to form respective molecular chains [FIG. 2 (a)].

Each of the molecular chains 1a and 1b has a closed cyclic chain structure composed of a TPT10 molecule and a Zn10 atom as the shortest closed cyclic chain structure [FIG. 2 (b)].
These molecular chains 1a and 1b can be regarded as a helical hexagonal three-dimensional network structure having a pitch along the (010) axis of 15 mm [FIG. 2 (c)].

The molecular chains 1a and 1b do not share the same zinc (II) ion and are independent of each other. Then, a three-dimensional skeleton organized as a whole is formed by interpenetrating each other in a nested manner so as to share the same space.
The single crystal of the polynuclear metal complex 1 having a three-dimensional skeleton has one kind of regularly arranged pores [FIG. 2 (d)].

The porosity of the single crystal of the polynuclear metal complex 1 is 50%.
The diameter of the inscribed circle of the single crystal pores of the polynuclear metal complex 1 is 5 to 8 mm.

(2) [(ZnBr ₂ ) ₃ (TPT) ₂ (solv) _a ] _b (7b)
Examples of the polynuclear metal complex represented by the formula (7b) include [(ZnBr ₂ ) ₃ (TPT) ₂ (PhNO ₂ ) ₅ (H ₂ O)] _n (polynuclear metal complex 2 described in JP-A-2008-214318. And all or part of the reaction solvent molecules in the polynuclear metal complex 2 are replaced with a substitution solvent.

The polynuclear metal complex 2 has a skeleton similar to the three-dimensional skeleton of the polynuclear metal complex 1 except that (ZnI ₂ ) is replaced by (ZnBr ₂ ).
The shape and size of the pores of the single crystal of the polynuclear metal complex 2 and the porosity were almost the same as those of the single crystal of the polynuclear metal complex 1.

(3) [(ZnI ₂ ) ₃ (TPT) ₂ (SA) (solv) _a )] _b (7c)
Examples of the polynuclear metal complex represented by the formula (7c) include [(ZnI ₂ ) ₃ (TPT) ₂ (TPH) (PhNO ₂ ) _3.9 (MeOH) _1.8 ] described in JP-A-2006-188560. _n (polynuclear metal complex 3), [(ZnI ₂ ) ₃ (TPT) ₂ (PER) (PhNO ₂ ) ₄ ] _n (polynuclear metal complex 4), or all of the reaction solvent molecules in these polynuclear metal complexes or The one obtained by exchanging a part with a substitution solvent can be mentioned.

The three-dimensional skeleton of the polynuclear metal complex 3 is shown in FIGS.
The three-dimensional skeleton of the polynuclear metal complex 3 is composed of two molecular chains 1A and 1B and a triphenylene molecule that is a skeleton-forming aromatic compound.
In the molecular chains 1A and 1B, each zinc (II) ion has two iodide ions and two TPT pyridyl groups coordinated in a tetracoordinate tetrahedral form. Then, the molecular chains are formed by three-dimensionally connecting the structures containing zinc (II) ions with TPT.
The molecular chains 1A and 1B do not share the same zinc (II) ion and are independent of each other. Then, a three-dimensional skeleton organized as a whole is formed by interpenetrating each other in a nested manner so as to share the same space.

  In the polynuclear metal complex 3, the triphenylene molecule (2) contains tris (4-pyridyl) triazine [TPT (1a)] of the molecular chain 1A and tris (4-pyridyl) triazine [TPT ( 1b)] is firmly inserted (intercalated) with the π plane [FIG. 3B]. At this time, the triphenylene molecule is stabilized by the π-π interaction between TPT (1a) and TPT (1b) and functions as a part of the three-dimensional skeleton of the polynuclear metal complex 3. In addition, FIG.3 (b) is a figure when the part enclosed with the line in Fig.3 (a) is seen from the side.

The single crystal of the polynuclear metal complex 3 has two types of regularly arranged pores (pores A and B) [FIG. 3 (c)]. The pores A and B are regularly formed between stacked structures in which TPT and TPH are alternately stacked.
The pore A has a substantially cylindrical shape and is substantially surrounded by hydrogen atoms present on the side edges of the infinite number of stacked TPTs and TPHs on the π plane.
On the other hand, the pore B has a substantially triangular prism shape, and among the three surfaces forming the triangular prism, two are surrounded by the π plane of the TPT, and the other is an infinite number of stacked TPT and TPH. Surrounded by hydrogen atoms present on the side edge of the π plane.
The pores A and B have an elongated shape that is slightly meandered.

The porosity of the single crystal pores of the polynuclear metal complex 3 is 28%.
The diameter of the inscribed circle of the single crystal pore A of the polynuclear metal complex 3 is 5 to 8 mm.
The diameter of the inscribed circle of the single crystal pore B of the polynuclear metal complex 3 is 5 to 8 mm.

The polynuclear metal complex 4 has a skeleton structure similar to that of the polynuclear metal complex 3 except that a perylene molecule is inserted between two TPTs instead of the triphenylene molecule of the polynuclear metal complex 3.
The shape and size of the pores of the single crystal of the polynuclear metal complex 4 and the porosity were almost the same as those of the single crystal of the polynuclear metal complex 3.

(4) [(Co (NCS) ₂ ) ₃ (TPT) ₄ (solv) _a ] _b (7d)
As the polynuclear metal complex represented by the formula (7d), [(Co (NCS) ₂ ) ₃ (TPT) ₄ (DCB) ₂₅ (MeOH) ₅ ] _n (polynuclear metal complex 5) described in WO2011 / 062260 And those obtained by exchanging all or part of the reaction solvent molecules in the polynuclear metal complex 5 with a substitution solvent.

The three-dimensional skeleton of the polynuclear metal complex 5 is shown in FIG.
The polynuclear metal complex 5 has a [Co ₆ (TPT) ₄ ] structure composed of six cobalt ions and four TPTs as structural units. This structural unit has an octahedral three-dimensional shape, and cobalt ions are arranged at six vertices of the octahedron [FIG. 4B]. In each cobalt (II) ion, four pyridyl groups of TPT and two thiocyanate ions are coordinated in a hexacoordinate octahedral form. FIG. 4B is an enlarged view of a portion surrounded by a line in FIG.
Then, the _[Co 6 _{(TPT) 4]} while sharing cobalt ions located at each vertex of the structure, _[Co 6 _{(TPT) 4]} structure by connecting in three dimensions, _[Co 6 (TPT) ₄ ] A pore is formed between the structures [FIG. 4 (c)].
The structural unit has a hollow inside.

The porosity of the single crystal of the polynuclear metal complex 5 is 78%. This value is a value calculated by combining the pores and the hollow volume.
The diameter of the inscribed circle of the single crystal pores of the polynuclear metal complex 5 is 10 to 18 mm.

  In the method of the present invention, the polydentate ligand (TPT) and the skeleton-forming aromatic compound in the polynuclear metal complex represented by the formulas (7a) to (7d) are substituted with a functional group (b). It has the same three-dimensional skeleton structure as the polynuclear metal complex represented by the formulas (7a) to (7d) obtained by using a bidentate ligand or a skeleton-forming aromatic compound, and the functional group (b) A single crystal of a polynuclear metal complex having the above can be used as a single crystal of a porous compound.

In addition to the polynuclear metal complex having a polydentate ligand represented by the above formula (1), the polynuclear metal complex is known as a porous coordination polymer (PCP) or a metal organic structure (MOF). The polynuclear metal complex can also be used. For example, in the Sigma-Aldrich brochure published in September 2012 (Basics of Materials Science No.7-Basics of Porous Coordination Polymers (PCP) / Metal Organic Structures (MOF))
[Cu ₂ (bzdc) ₂ (pyz)] _n
(“Bzdc” represents 2,3-pyrazinedicarboxylic acid, “pyz” represents pyrazine, and n represents any number).
[Zn ₂ (14bdc) ₂ (dabco)] _n
(“14bdc” represents 1,4-benzenedicarboxylic acid, “dabco” represents 1,4-diazabicyclo [2.2.2] octane, and n represents any number).
[Cu (dhbpc) ₂ (bpy)] _n
(“H ₃ dhbpc” represents 4,4′-dihydroxybiphenyl-3-carboxylic acid, “bpy” represents 4,4′-bipyridyl, and n represents any number).
[Cr (btc) ₂ ] _n
(“H ₃ btc” represents 1,3,5-benzenetricarboxylic acid, and n represents an arbitrary number.) And other polynuclear metal complexes are described.

  In the method of the present invention, instead of the polydentate ligand in these polynuclear metal complexes, a single crystal of the polynuclear metal complex obtained using the polydentate ligand into which the functional group (b) is introduced, It can be used as a single crystal of a porous compound.

The method for synthesizing the polynuclear metal complex is not particularly limited, and a known method can be used.
For example, the Sigma-Aldrich brochure published in September 2012 (Material Science Fundamental No. 7-Porous Coordination Polymer (PCP) / Metal Organic Structure (MOF) Fundamentals) includes multidentate ligands, etc. A solution method in which a solution containing a metal ion and a solution containing a metal ion, etc. are mixed; a solvent, a polydentate ligand, a metal ion, etc. are placed in a pressure vessel, and after the pressure vessel is sealed, the temperature exceeds the boiling point of the solvent Hydrothermal method in which a hydrothermal reaction is carried out by heating; a microwave method in which a solvent, a polydentate ligand, a metal ion, etc. are placed in a container and microwave irradiation; a solvent, a polydentate ligand in the container , Ultrasonic methods of putting metal ions, etc., and irradiating ultrasonic waves; solid-phase synthesis methods of mechanically mixing polydentate ligands, metal ions, etc. without using a solvent; Using this method, a single crystal of a polynuclear metal complex can be obtained.

Among these, since a special apparatus etc. are not required, the solution method is preferably used.
As the solution method, for example, the solvent solution of the second solvent of the metal ion-containing compound is added to the solvent solution of the first solvent of the polydentate ligand, and the polydentate ligand and the metal ion are mixed at a predetermined ratio. In addition, the method of leaving still at 0-70 degreeC for several hours to several days as it is is mentioned.

The metal ion-containing compound is not particularly limited. For example, a compound represented by the formula: MX _n can be mentioned. Here, M represents a metal ion, X represents a counter ion, and n represents the valence of M.

Specific examples of X include F ⁻ , Cl ⁻ , Br ⁻ , I ⁻ , SCN ⁻ , NO ₃ ⁻ , ClO ₄ ⁻ , BF ₄ ⁻ , SbF ₄ ⁻ , PF ₆ ⁻ , AsF ₆ ⁻ , CH ₃ CO ₂ ^-, and the like.

  Examples of the reaction solvent (first solvent and second solvent) used include aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, 1,2-dichlorobenzene, nitrobenzene; n-pentane, n-hexane, n -Aliphatic hydrocarbons such as heptane; Alicyclic hydrocarbons such as cyclopentane, cyclohexane and cycloheptane; Nitriles such as acetonitrile and benzonitrile; Sulfoxides such as dimethyl sulfoxide (DMSO); N, N-dimethyl Amides such as formamide and n-methylpyrrolidone; ethers such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane and 1,4-dioxane; alcohols such as methanol, ethanol and isopropyl alcohol; acetone, methyl ethyl ketone and cyclohexanone No Cellosolves such as ethyl cellosolve; Halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane; Esters such as methyl acetate, ethyl acetate, ethyl lactate, and ethyl propionate; Water; Etc. These solvents can be used alone or in combination of two or more.

When it is desired to obtain a relatively large polynuclear metal complex single crystal, it is preferable to use the first solvent and the second solvent that are not compatible with each other (that is, separated into two layers). For example, a method using nitrobenzene, dichlorobenzene, a mixed solvent of nitrobenzene and methanol, a mixed solvent of dichlorobenzene and methanol as the first solvent, and methanol as the second solvent can be mentioned.
Moreover, each of the polynuclear metal complexes having the same three-dimensional skeleton structure as the polynuclear metal complexes 1 to 5 can be synthesized according to the method described in the above-mentioned document.

(Iv) A step of bringing a single crystal of a porous compound into contact with a solvent solution containing an organic compound (A) In the present invention, a method of bringing a single crystal of a porous compound into contact with a solvent solution containing the organic compound (A) Is not particularly limited. For example, a method in which the single crystal is immersed in a solvent solution containing the organic compound (A), and after the single crystal is packed in a capillary, the solvent solution containing the organic compound (A) is passed through the capillary. Methods and the like.
Especially, since the solvent solution containing the organic compound (A) can be efficiently contacted with the single crystal of the porous compound, the method of immersing the single crystal of the porous compound in the solvent solution containing the organic compound (A) Is preferred.

  When immersing the single crystal of the porous compound in the solvent solution containing the organic compound (A), the A value calculated from the following formula (I) is 100 or less, preferably 0.1 to 30, more preferably It is preferable to immerse a single crystal of the porous compound in an amount of 1 to 5.

  In the formula (I), X represents the mass of the organic compound (A) in the solvent solution, and Y fills all pores and hollows in the single crystal of the porous compound with a substance having a specific gravity of 1. Represents the mass of the substance having the specific gravity of 1 required.

  When the A value is 0.1 or more, the molecules of the organic compound (A) are sufficiently taken into the pores and hollows of the single crystal of the porous compound, and it becomes easy to obtain a high-quality crystal structure analysis sample. On the other hand, even if the A value is large, a target crystal structure analysis sample can be obtained, but an effect commensurate with it cannot be obtained, and the organic compound (A) is likely to be wasted.

  The number of single crystals to be immersed is not particularly limited. When the amount of the organic compound (A) is extremely small, a target crystal structure analysis sample can be obtained by immersing one single crystal. Moreover, when there is a margin in the amount of the organic compound (A), two or more single crystals of the same kind of porous compound may be immersed, or single crystals of different kinds of porous compounds may be immersed simultaneously.

  After immersing the porous crystal single crystal in the solvent solution containing the organic compound (A), the solvent solution may be evaporated by volatilizing the solvent under mild conditions. By performing this treatment, the molecules of the organic compound (A) can be efficiently taken into the pores and hollows of the single crystal of the porous compound.

Although the immersion conditions (concentration conditions) at this time are not particularly limited, the temperature of the solvent solution is preferably 0 to 180 ° C, more preferably 0 to 80 ° C, and further preferably 20 to 60 ° C.
The immersion time (concentration time) is usually 6 hours or longer, preferably 12 to 168 hours, more preferably 24 to 78 hours.

The volatilization rate of the solvent is preferably 0.1 to 1000 μL / 24 hours, more preferably 1 to 100 μL / 24 hours, and still more preferably 5 to 50 μL / 24 hours.
When the volatilization rate of the solvent is too fast, there is a possibility that a high-quality crystal structure analysis sample cannot be obtained. On the other hand, if the volatilization rate of the solvent is too slow, it is not preferable from the viewpoint of working efficiency.

  Although the temperature at which the solvent is volatilized depends on the boiling point of the organic solvent to be used, it is usually 0 to 120 ° C, preferably 15 to 60 ° C.

The operation of immersing the porous compound single crystal in the solvent solution containing the organic compound (A) and then volatilizing the solvent to concentrate the solvent solution is carried out under normal pressure or under reduced pressure. Alternatively, it may be performed under pressure.
The solvent is evaporated, the pressure during the operation of concentrating the solvent solution is normally, 1 to 1 × ¹⁰ 6 Pa, preferably from 1 × 10~1 × ¹⁰ 6 Pa.
As described above, the volatilization rate of the solvent can be adjusted appropriately by adjusting the temperature and pressure during the operation of concentrating the solvent solution.

  In the present invention, before contacting the single crystal of the porous compound with the solvent solution containing the organic compound (A), the solvent of the organic compound (A) is placed in the pores and hollows of the single crystal of the porous compound. You may provide the process of taking in the molecule | numerator of the solvent used for a solution. By providing this step, the solvent (reaction solvent) molecules used in the synthesis of the porous compound are removed from the pores and hollows, and the organic compound (A) can be easily replaced with the solvent. It is possible to efficiently produce a sample for crystal structure analysis of good quality.

As a method of incorporating the molecules of the solvent used in the solvent solution of the organic compound (A) into the pores and hollows of the single crystal of the porous compound, the single crystal to be used is previously converted into the solvent solution containing the organic compound (A). The method of immersing in the solvent used for preparation of this is mentioned.
Although the immersion conditions at this time are not particularly limited, the temperature of the solvent is usually 0 to 70 ° C., preferably 10 to 60 ° C., more preferably 20 to 50 ° C., and the immersion time is usually 6 hours or more. , Preferably 12 to 168 hours, more preferably 24 to 78 hours.

(V) Sample for crystal structure analysis The sample for crystal structure analysis obtained by the method of the present invention is such that the molecules of the organic compound (A) are regularly arranged in the pores and hollows of the single crystal of the porous compound. It has been made.
Here, “the molecules of the organic compound (A) are regularly arranged” means that the molecules of the organic compound (A) are porous without being disturbed to such an extent that the structure can be determined by crystal structure analysis. It means that the compound is regularly accommodated in the pores and hollows of the single crystal of the compound.

  The sample for crystal structure analysis obtained by the method of the present invention was irradiated with MoKα rays (wavelength: 0.71Å) generated at a tube voltage of 24 kV and a tube current of 50 mA, and diffracted X-rays were detected by a CCD detector. Sometimes it is preferable to be able to determine the molecular structure with a resolution of at least 1.5 mm.

  If the crystal structure analysis sample obtained by the method of the present invention can determine the structure of the organic compound (A), it is organic in all pores and hollows in the single crystal of the porous compound. It is not necessary that the molecule of compound (A) is incorporated. For example, the solvent used in the solvent solution of the organic compound (A) may be taken into a part of the pores and hollows in the single crystal of the porous compound.

The crystal structure analysis sample obtained by the method of the present invention preferably has an organic compound (A) molecule occupancy of 10% or more.
The occupation ratio is a value obtained by crystal structure analysis, and actually exists in a single crystal when the amount of guest molecules (molecules of organic compound (A)) in an ideal inclusion state is 100%. It represents the amount of guest molecules.

  Even if the sample for crystal structure analysis obtained by the method of the present invention is an organic compound (A) that can be obtained only in a trace amount or an organic compound (A) that is liquid at room temperature (20 ° C.), the crystal structure analysis method It is possible to clarify the structure.

  The target crystal structure analysis sample can be obtained by the method of the present invention because the single crystal of the porous compound used in the present invention aligns the molecules of the organic compound (A) as described below. This is probably because it functions as a “place”.

First, as can be seen from the fact that single crystals of protein molecules are obtained, many substances are considered to have a self-accumulation ability, and although there are differences in degree, it is possible to perform the crystallization operation under optimal crystallization conditions. If possible, the possibility of obtaining a single crystal is considered sufficient.
However, there are many substances in the world where single crystals cannot be obtained because it is difficult to find the optimal crystallization conditions or it is not possible to secure an amount of sample that can sufficiently examine the crystallization conditions. It is.
The single crystal of the porous compound used in the present invention is considered to provide a “field” for crystallization of such a substance.
That is, the organic compound (A) molecules are taken into the single crystal pores and / or hollows by constructing the pores and / or hollows regularly arranged three-dimensionally in the single crystal in advance. The self-accumulation ability of the organic compound (A) molecules is enhanced due to the influence of the regularity of the “field”, and the orientation of the organic compound (A) molecules is naturally aligned. It is considered that a sample for use is obtained.

  Furthermore, the single crystal of the porous compound used in the present invention has a functional group (b) in the pores and / or hollows. Therefore, the molecule of the organic compound (A) taken into the pores and / or hollows is accommodated in a thermodynamically stabilized state by the interaction between the functional group (a) and the functional group (b). .

As will be described below, this property is considered to be particularly effective when the amount of the organic compound (A) in the sample solution is very small.
First, when the amount of the organic compound (A) in the sample solution is small, the amount of the organic compound (A) molecules that enter the pores and / or hollows per unit time is larger than when the organic compound (A) is present in a large amount. Expected to be less. Therefore, in order to efficiently prepare a sample for crystal structure analysis when the amount of the organic compound (A) is very small, the molecules of the organic compound (A) once taken into the pores and / or hollows are exposed to the outside. It is important to prevent it from being released.
In the method of the present invention, as described above, the molecule of the organic compound (A) is thermodynamically stabilized in the pores and / or hollows, and thus is hardly released to the outside.
Therefore, by using the method of the present invention, a sample for crystal structure analysis can be efficiently produced even when the amount of the organic compound (A) is very small.

In addition, when the amount of the organic compound (A) in the sample solution is small, there is a tendency that a sample for crystal structure analysis with a low occupancy rate of the molecule of the organic compound (A) is obtained (that is, inside the pores and / or hollows). In addition, space is easily generated and solvent molecules are easily included.)
In order to accurately determine the molecular structure of the organic compound (A) using such a crystal structure analysis sample, the molecules of the included organic compound (A) must be aligned more disorderly. Becomes important.
In general, a single crystal (three-dimensional skeleton) in which guest molecules such as the organic compound (A) are not included is apt to collapse more easily.
In the method of the present invention, since there is an interaction between the functional group (a) and the functional group (b), the directions of the molecules of the organic compound (A) are more easily aligned. Moreover, it can be considered that the interaction between the functional group (a) and the functional group (b) has an effect of further stabilizing the three-dimensional skeleton of the single crystal.
Therefore, by using the method of the present invention, even when the amount of the organic compound (A) is small, a sample for crystal structure analysis of good quality can be prepared, and the molecular structure of the organic compound (A) can be accurately determined. Can be determined.

2) Molecular structure determination method of organic compound The molecular structure determination method of an organic compound of the present invention has a functional group (a) by crystal structure analysis using a crystal structure analysis sample obtained by the method of the present invention. It includes the step of determining the molecular structure of the organic compound (A).
In the method of the present invention, any of X-ray diffraction and neutron diffraction can be used.
When determining the molecular structure of the organic compound (A) by the method of the present invention, a conventional method is used except that the sample for crystal structure analysis obtained by the above method is mounted instead of the conventional single crystal. Can be used.

According to the molecular structure determination method of the present invention, the molecular structure of the organic compound (A) having the functional group (a) can be determined efficiently.
Therefore, according to the molecular structure determination method of the present invention, the cost and time required for analysis of trace amounts of impurities contained in agricultural drugs and their raw materials, trace amounts of impurities contained in raw materials of electronic components, various metabolites, etc. Can be reduced. Even if the organic compound (A) having the functional group (a) can be obtained only in a very small amount, or even when the organic compound (A) having the functional group (a) is not solid at the measurement temperature, the molecule It is possible to determine the structure.

  Hereinafter, the present invention will be described more specifically with reference to examples and comparative examples. However, the present invention is not limited to these examples.

(Equipment)
(1) Single-crystal X-ray structure analysis It was performed using an APEX II / CCD diffractometer [source: Mo-Kα ray (wavelength: 0.71 （), output: 50 mA, 24 kV] manufactured by Bruker.
(2) Elemental analysis It was performed using MT-6 manufactured by YANACO.

(Production Example 1)
A single crystal of a polynuclear metal complex having 1-aminotriphenylene as a skeleton-forming aromatic compound was obtained by the method described in Examples of WO2007 / 102594.
(Production Example 2)
A single crystal of a polynuclear metal complex containing cobalt was obtained by the method described in Example 1 of WO2011 / 062260.

Example 1
A single crystal of the polynuclear metal complex obtained in Production Example 1 is placed in a microvial, to which 5 μl of a cyclohexane solution of 4,4,4-trifluorobutyric acid (1 mg / ml) having a structure represented by the following formula and 45 μl of cyclohexane are added. The sample for crystal structure analysis was obtained by slowly distilling off the solvent at 50 ° C. over 2 days. X-ray crystal structure analysis was performed using this crystal structure analysis sample.
The crystallographic data is shown in Table 1 and the crystal structure is shown in FIG.

(Example 2)
A single crystal of the polynuclear metal complex obtained in Production Example 1 was placed in a microvial, to which 5 μl of a cyclohexane solution of cis-9-hexadecenoic acid (1 mg / ml) having a structure represented by the following formula and 45 μl of cyclohexane were added, and 50 ° C. The sample for crystal structure analysis was obtained by slowly distilling off the solvent over 2 days. X-ray crystal structure analysis was performed using this crystal structure analysis sample.
The crystallographic data is shown in Table 2 and the crystal structure is shown in FIG.

(Example 3)
A single crystal of the polynuclear metal complex obtained in Production Example 1 is placed in a microvial, to which 5 μl of a cyclohexane solution of petrothelic acid (1 mg / ml) having a structure represented by the following formula and 45 μl of cyclohexane are added, and the mixture is taken at 50 ° C. for 2 days. The sample for crystal structure analysis was obtained by slowly distilling off the solvent. X-ray crystal structure analysis was performed using this crystal structure analysis sample.
The crystallographic data is shown in Table 3, and the crystal structure is shown in FIG.

(Comparative Example 1)
The single crystal of the polynuclear metal complex obtained in Production Example 2 is placed in a microvial, to which 5 μl of a cyclohexane solution of 4,4,4-trifluorobutyric acid (1 mg / ml) and 45 μl of cyclohexane are added, and at 50 ° C. for 2 days. The solvent was slowly distilled off over a period of time. However, since the single crystal was deteriorated, the crystal structure analysis could not be performed.
It is considered that trifluoroacetic acid is not taken into the pores and hollows regularly, the three-dimensional skeleton is not stabilized, and the crystal is deteriorated.

1: Crystal plane X
2: Crystal plane Y
3: Pore 4: Direction in which the pore extends

Claims (11)

A method for preparing a crystal structure analysis sample for determining a molecular structure of an organic compound (A) having a functional group (a),
Three-dimensional skeleton composed of one or two or more molecular chains, or one or two or more molecular chains and a skeleton-forming compound, and three-dimensionally regularly formed by being partitioned by the three-dimensional skeleton A porous compound having a pore and / or a hollow, and the three-dimensional skeleton having a functional group (b) interacting with the functional group (a) in the pore and / or hollow. By contacting the crystal with a solvent solution containing the organic compound (A),
For crystal structure analysis, comprising a step of preparing a sample for crystal structure analysis in which the molecules of the organic compound (A) are regularly arranged in the pores and / or hollows of the single crystal Sample preparation method.   The interaction between the functional group (a) and the functional group (b) is an electrostatic interaction, a hydrogen bond, a hydrophobic interaction, a π-π interaction, or a CH-π interaction. Of preparing a sample for crystal structure analysis.   The functional group (a) has a group having at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom, an alkyl group which may have a halogen atom, and a halogen atom. The method for producing a sample for crystal structure analysis according to claim 1 or 2, which is an aryl group which may be present or a group containing a metal ion.   The functional group (b) has a group having at least one atom selected from the group consisting of a nitrogen atom, an oxygen atom, a sulfur atom and a phosphorus atom, an alkyl group which may have a halogen atom, and a halogen atom. The method for producing a sample for crystal structure analysis according to any one of claims 1 to 3, wherein the sample may be an aryl group or a group containing a metal ion.   The method for producing a crystal structure analysis sample according to claim 1, wherein the content of the organic compound (A) in the solvent solution containing the organic compound (A) is 5 mg or less.   The sample for crystal structure analysis according to any one of claims 1 to 5, wherein the porous compound is a polynuclear metal complex containing a ligand having two or more coordination sites and a metal ion as a central metal. Manufacturing method.   The porous compound is a polynuclear metal complex including a ligand having two or more coordination sites, a metal ion as a central metal, and a skeleton-forming aromatic compound having a functional group (b). The manufacturing method of the sample for crystal structure analysis in any one of 1-6. The ligand having two or more coordination sites is represented by the following formula (1):

(In the formula, Ar represents a trivalent aromatic group which may have a substituent. X ^{1 to} X ³ are each independently a divalent organic group, or Ar and Y ¹ to Y ^3. (Y ¹ to Y ³ each independently represents a monovalent organic group having a coordination site.)
The method for producing a sample for crystal structure analysis according to claim 6 or 7, wherein the sample is a tridentate ligand represented by the following formula.   The method for producing a sample for crystal structure analysis according to any one of claims 6 to 8, wherein the metal ion as the central metal is an ion of a metal of Groups 8 to 12 of the periodic table.   The means for bringing the single crystal into contact with the solvent solution containing the organic compound (A) is for immersing the single crystal in the solvent solution containing the organic compound (A). A method for producing a sample for crystal structure analysis according to claim 1.   A method for determining a molecular structure of an organic compound having a functional group, wherein the functional group (a) is obtained by a crystal structure analysis method using the crystal structure analysis sample obtained by the method according to claim 1. The method for determining the molecular structure of an organic compound having a functional group, comprising the step of determining the molecular structure of the organic compound (A) having a functional group).

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