WO2014132467A1

WO2014132467A1 - Carbon nanocage and intermediate thereof, and methods respectively for producing said carbon nanocage and said intermediate

Info

Publication number: WO2014132467A1
Application number: PCT/JP2013/072775
Authority: WO
Inventors: 健一郎伊丹; 泰知瀬川; 克磨松井
Original assignee: 国立大学法人名古屋大学
Priority date: 2013-02-27
Filing date: 2013-08-26
Publication date: 2014-09-04
Also published as: JPWO2014132467A1

Abstract

The purpose of the present invention is to provide a method for synthesizing a carbon nanocage, which can be used as a connection unit for a branched carbon nanotube, in a simple manner. A box-shaped compound (B) in which 8 or more rings are bonded through single bonds, wherein sp2 hybrid carbon atoms or sp3 hybrid carbon atoms which exist in each of the rings are bonded to each other in each of the rings, said box-shaped compound (B) having 2 to 4 specific groups, 6 1,4-cyclohexylene groups each of which may have a substituent and 0 or more bivalent aromatic hydrocarbon groups each of which may have a substituent. A cyclohexane ring moiety in the box-shaped compound is converted to a benzene ring, thereby producing a carbon nanocage which can be used as a connection unit for a branched carbon nanotube.

Description

Carbon nanocages and intermediates thereof, and production methods thereof

The present invention relates to a carbon nanocage, an intermediate thereof, and a production method thereof.

Conventionally, as a nanostructure containing a carbon atom, a carbon nanotube having a structure in which a two-dimensional graphene sheet is wound in a cylindrical shape, a ring-shaped carbon nanotube made of the carbon nanotube, and the like are known.

Carbon nanotubes have extremely high mechanical strength, can withstand high temperatures, and have excellent properties such as efficient electron emission when voltage is applied. Applications in various fields such as life science are expected.

As a method for producing a carbon nanotube, an arc discharge method, a laser fanes method, a chemical vapor deposition method, and the like are known. However, these production methods have a problem that carbon nanotubes of various thicknesses and lengths can be obtained only in the form of a mixture.

Recently, instead of tubular nanostructures having a certain length or longer due to continuous bonding of carbon atoms such as carbon nanotubes, annular nanostructures are being studied. For example, cycloparaphenylene (CPP) is a simple and beautiful molecule in which benzene is cyclically linked at the para position, and in recent years, it has become clear that it has a very unique structure and properties. In particular, this CPP has different diameters depending on the number of benzene rings constituting it, its properties are different, and if it can be made separately, it can be expected to develop into carbon nanotubes having different diameters. There is a demand for completely creating different numbers of CPPs. However, although CPP is known as a method for obtaining a mixture, there are very few examples of successful selective synthesis.

The present inventors have succeeded in synthesizing various cycloparaphenylene compounds by using a cyclocyclophenylene precursor using a cyclohexane ring as a bent portion (

Patent Documents

1 and 2, Non-Patent Document 1). This cycloparaphenylene compound was difficult to synthesize because benzene, which was originally a flat surface, was distorted in a ring shape, but due to the successful elimination of strain at the synthesis stage using a unique method, various sizes and shapes were obtained. This made it possible to synthesize cycloparaphenylene compounds.

International Publication No. 2011/099588 Pamphlet International Publication No. 2011-111719 Pamphlet

This cycloparaphenylene compound is the shortest partial skeleton of linear carbon nanotubes, and is an ideal building block for complete chemical synthesis of linear carbon nanotubes with controlled thickness and side structure.

On the other hand, the above-mentioned cycloparaphenylene compound is a building block for the complete chemical synthesis of linear carbon nanotubes, but it is a branching carbon nanotube that is expected to be applied to the electronics field as the smallest transistor, logic gate, etc. There is still no synthesis method for carbon nanogauge that can be a bonding unit, and there is still no guideline for complete chemical synthesis of branched carbon nanotubes.

From such a viewpoint, an object of the present invention is to provide a method for easily synthesizing a carbon nanocage that can be a junction unit of branched carbon nanotubes.

As a result of intensive studies in view of the above problems, the present inventors applied a synthesis method of a cycloparaphenylene compound and used a specific three-pronged unit as a starting material, so that a carbon nanocage that is a cage compound was obtained. It was found that it can be synthesized. Specifically, a specific trigeminal unit is homocoupled, or a specific trigeminal unit and another unit are cross-coupled to synthesize a box-shaped compound having no strain, and the cyclohexane ring part of this compound is synthesized. It has been found that carbon nanocages having strains and uniformly curved arches can be synthesized by aromatization. The present invention has been completed as a result of further research based on such knowledge. That is, the present invention includes the configurations of items 1 to 10 below.

A box-shaped compound (B) in which at least 1.8 rings are linked by a single bond,
The rings are bonded to each other with sp2 hybrid carbon atoms or sp3 hybrid carbon atoms present in the ring,
(1) Formula:

2 to 4 groups represented by
(2) consisting of 6 optionally substituted 1,4-cyclohexylene groups and (3) 0 or more divalent aromatic hydrocarbon groups optionally having substituents , Box-shaped compounds.

Item 2. Formula (IIa):

[Wherein R ² is the same or different and each represents a general formula (IIa-1):

(Wherein R ³ is the same or different, and each represents a hydrogen atom or a hydroxyl-protecting group; R ⁴ is the same or different, and each is a divalent aromatic hydrocarbon group optionally having a substituent; The same or different, each being an integer of 0 or more.)
It is a bivalent group shown by these. ]
Item 2. The box-shaped compound according to Item 1, which is a compound represented by:

Item 3.8 is a cage compound (A) in which two or more rings are linked by a single bond,
The rings have sp2 hybrid carbon atoms present in the rings bonded to each other,
(1) Formula:

And (3) a method for producing a cage compound, comprising (3) 6 or more divalent aromatic hydrocarbon groups which may have a substituent,
A box-shaped compound (B) in which eight or more rings are linked by a single bond,
The rings are bonded to each other with sp2 hybrid carbon atoms or sp3 hybrid carbon atoms present in the ring,
(1) Formula:

2 to 4 groups represented by
(2) consisting of 6 optionally substituted 1,4-cyclohexylene groups and (3) 0 or more divalent aromatic hydrocarbon groups optionally having substituents The manufacturing method provided with the conversion process which converts the cyclohexane ring part which a box-shaped compound has into a benzene ring.

Item 4. Before the conversion step,
General formula (III):

[Wherein R ³ is the same or different and each represents a hydrogen atom or hydroxyl-protecting group; R ⁴ is the same or different and each represents a divalent aromatic hydrocarbon group optionally having a substituent; The same or different, each an integer greater than or equal to 0; Y is the same or different and each represents a halogen atom or general formula (III-1):

(Wherein R ⁵ is the same or different and each represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R ⁵ is bonded to each other to form a ring with adjacent —O—B—O—. May be.)
It is group shown by these. ]
Item 4. The production method according to Item 3, comprising a coupling step of coupling the compound (III) represented by the formula:

Item 5.8 is a cage compound in which at least eight rings are linked by a single bond,
The rings have sp2 hybrid carbon atoms present in the rings bonded to each other,
(1) Formula:

A cage compound comprising 2 to 4 groups represented by the formula (2) and (2) 6 or more divalent aromatic hydrocarbon groups which may have a substituent.

Item 6. Formula (Ia):

[Wherein, R ¹ is the same or different and each represents a general formula (Ia-1):

(In the formula, R ⁴ is the same or different and each is a divalent aromatic hydrocarbon group optionally having a substituent; n is the same or different and each is an integer of 0 or more.)
It is a bivalent group shown by these. ]
Item 6. The cage compound according to Item 5, which is a compound represented by:

Item 7. Item 7. The cage compound according to Item 6, wherein R ⁴ is a group having a bond at the para position.

Item 8. Item 8. The cage compound according to any one of Items 5 to 7, wherein the total number of rings is 8 to 22.

Item 9.8 is a box-shaped compound (B) in which not less than 9.8 rings are linked by a single bond,
The rings are bonded to each other with sp2 hybrid carbon atoms or sp3 hybrid carbon atoms present in the ring,
(1) Formula:

2 to 4 groups represented by
(2) consisting of 6 optionally substituted 1,4-cyclohexylene groups and (3) 0 or more divalent aromatic hydrocarbon groups optionally having substituents A method for producing a box-shaped compound comprising:
General formula (III):

(Wherein R ⁵ is the same or different and each represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R ⁵ is bonded to each other to form a ring with adjacent —O—B—O—. May be.)
It is group shown by these. ]
The manufacturing method provided with the coupling process which couples compound (III) shown by these.

Item 10. General formula (III):

(Wherein R ⁵ is the same or different and each represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R ⁵ is bonded to each other to form a ring with adjacent —O—B—O—. May be.)
It is group shown by these. ]
A compound represented by

According to the present invention, a carbon nanocage that is a cage compound can be synthesized by a simple technique using a commercially available compound. As described above, this carbon nanocage is expected as a junction unit of branched carbon nanotubes, and precise bottom-up synthesis of branched carbon nanotubes is expected.

Also, this carbon nanocage can change the space existing inside depending on the number of rings constituting it, and can incorporate guest molecules here. As an example, the size (diameter) of the internal space can be changed according to the number of rings as follows.

Furthermore, this carbon nanocage is excellent in handleability (for example, it is a white solid that dissolves well in most organic solvents and does not decompose even at a high temperature of 300 ° C. or higher). Carbon nanocages absorb light well and have strong fluorescence (for example, in the case of [6, 6, 6] cage, it absorbs one photon, absorbs two photons, and has strong blue fluorescence. [4] .4.4] Cages and [5.5.5] cages absorb one photon and have strong blue fluorescence. By adjusting the size of the carbon nanocage, desired optical properties can also be obtained.

From such a viewpoint, the carbon nanocage synthesized by the present invention is not only expected as a junction unit of branched carbon nanotubes, but also an organic EL material, an organic transistor material, an optical recording material, a high-density optical storage, a living body It can be used in various applications such as fluorescence imaging of molecules, photosensors for guest molecules.

[6.6.6] carbon nanocages (1) obtained in Example 3 in chloroform (0.57 mM) at 573 nm with different incident powers (P = 0.04, 0.12, 0.21, 0.30 mW in order from the top). ) Open aperture Z-scan trace. Fits well with theoretical curves. The horizontal axis is the sample position Z, and the vertical axis is the normalized transmittance far from the focal point (Z = 0) (| Z | >> Z _R ). Each trace has been shifted to 0.02 for readability. Opening 2 ''',5'''-didecyl-p-septiphenyl (15 mM) in chloroform at 510 nm with different incident powers (P _i = 0.05, 0.14, 0.24, 0.34 mW in order from top) Aperture Z-scan trace. Fits well with theoretical curves. The horizontal axis is the sample position Z, and the vertical axis is the normalized transmittance far from the focal point (Z = 0) (| Z | >> Z _R ). Each trace has been shifted to 0.02 for readability. [6.6.6] is a plot of P _i versus q ₀ solution of the cage. A value of q ₀ was obtained from the curve fit of FIG. 2 ''',5''' - didecyl -p- is a plot of P _i versus q ₀ solution of Sepuchifeniru. A value of q ₀ was obtained from the curve fit of FIG. [4.4.4] Absorption and fluorescence spectra of cages, [5.5.5] cages and [6.6.6] cages. The solid line is the absorption spectrum of the [4.4.4] cage, [5.5.5] cage, and [6.6.6] cage in order from the left, and the broken line is [6.6 in order from the left. .6] Fluorescence spectra of cage, [5.5.5] cage and [4.4.4] cage. 1 is a drawing showing the structure of a trisubstituted benzene of protected tribromobenzene obtained in Example 1-3 by thermal vibration ellipsoid drawing software (ORTEP). Note that hydrogen atoms are omitted. It is drawing which shows the structure of the [4.4.4] cage obtained in Example 3-2 by thermal vibration ellipsoid drawing software (ORTEP). (A): overall appearance, (b): overview viewed from above, (c): packing mode structure, respectively. In all the figures, hydrogen atoms, tetrahydrofuran molecules, and diethyl ether molecules are omitted. It is drawing which shows the structure of the [4.4.4] cage obtained in Example 3-2 by thermal vibration ellipsoid drawing software (ORTEP). Note that hydrogen atoms are omitted. It is drawing which shows the structure of a [4.4.4] cage, a [5.5.5] cage, and a [6.6.6] cage. [6.6.6] Cage frontier molecular orbitals.

[1] Basket compound (A)
The cage compound (A) of the present invention is a cage compound (A) in which 8 or more rings are linked by a single bond,
The rings have sp2 hybrid carbon atoms present in the rings bonded to each other,
(1) Formula:

And (3) a cage compound comprising 6 or more divalent aromatic hydrocarbon groups which may have a substituent.

The number of units (1) possessed by the cage compound (A) of the present invention is 2 to 4, preferably 2 or 4, and more preferably 2. In the case of having two units (1), the cage compound (A) of the present invention has three uniform arches having strain.

In other words, the divalent aromatic hydrocarbon group as the unit (3) possessed by the cage compound (A) of the present invention is a divalent group having an aromatic ring, and 2 constituting this aromatic ring. Each of the hydrogen atoms bonded to one carbon atom is a group formed by elimination one by one. In addition, the hydrogen atom couple | bonded with carbon which comprises this aromatic ring may be the derivative group (divalent derivative group) substituted by the functional group. The cage compound (A) of the present invention may have a plurality of different aromatic hydrocarbon groups.

Examples of the aromatic ring include not only a benzene ring but also a ring obtained by condensing a plurality of benzene rings (benzene condensed ring), a ring obtained by condensing a benzene ring and other rings (hereinafter, a plurality of benzene rings are condensed). And a ring obtained by condensing a benzene ring with another ring may be simply referred to as a “fused ring”). Examples of the condensed ring include a pentalene ring, an indene ring, a naphthalene ring, an anthracene ring, a tetracene ring, a pentacene ring, a pyrene ring, a perylene ring, a triphenylene ring, an azulene ring, a heptalene ring, a biphenylene ring, an indacene ring, an acenaphthylene ring, Examples include a fluorene ring, a phenalene ring, a phenanthrene ring, and the like.

In addition, the substituent that the aromatic hydrocarbon group may have is not particularly limited, but a functional group that can impart a function that cannot be imparted by a hydrocarbon-only cyclic compound is preferable. Atoms, chlorine atoms, bromine atoms, iodine atoms, etc.); aryl groups optionally having substituents such as alkyl groups having 1 to 6 carbon atoms and alkoxy groups having 1 to 12 carbon atoms (4-methoxyphenyl groups, etc.) ), An alkoxy group having 1 to 12 carbon atoms, a hydroxy group, a boryl group, a silyl group, an amino group, and the like. Among these, a halogen atom is preferable. In addition, a chlorine atom is more preferable because it is introduced from the time of manufacturing raw materials and is not particularly likely to become a reaction point during the manufacturing process.

The unit (3) of the cage compound (A) of the present invention is a group having a divalent 6-membered aromatic ring or a divalent 6-membered heteroaromatic ring among the above rings, A group having a bond at the para position is preferred.

The ring forming the unit (3) is preferably a single ring or a condensed ring, and more preferably a single ring.

Among these, the unit (3) of the cage compound (A) of the present invention is preferably a divalent aromatic hydrocarbon group, particularly preferably a phenylene group (particularly 1,4-phenylene group) and a naphthylene group. (Especially 1,5-naphthylene group or 2,6-naphthylene group), more preferably phenylene group (especially 1,4-phenylene group).

When the cage compound (A) of the present invention has at least one condensed ring as the unit (3), the cage compound of the present invention can be a chiral cage compound. This is useful in that the chiral fullerene can be more efficiently included.

In the cage compound (A) of the present invention, the number of such units (3) is 6 or more, preferably 6 to 98, more preferably 6 to 48, still more preferably 6 to 28, and more. The number is preferably 6 to 18, particularly preferably 6, 12, 15, or 18. That is, the number of units (3) is preferably a multiple of three.

In the cage compound (A) of the present invention, the total number of rings is the total number of units (1) and units (3), which is 8 or more, preferably 8 to 100, more preferably 8 to The number is 50, more preferably 8 to 30, more preferably 8 to 22, particularly preferably 8, 14, 17, 20, or 22.

Such a cage compound (A) of the present invention is excellent in handleability (for example, it is a white solid which dissolves well in most organic solvents and does not decompose even at a high temperature of 300 ° C. or higher). Also, it absorbs light well and has strong fluorescence (for example, in the case of [6.6.6] cage, it absorbs one photon, absorbs two photons, and has strong blue fluorescence. Also, [4.4.4] The cage and [5.5.5] cages absorb one photon and have strong blue fluorescence.) Therefore, the cage compound (A) of the present invention is not only expected as a junction unit of branched carbon nanotubes, but also organic EL materials, organic transistor materials, optical recording materials, high-density optical storage, and biomolecular fluorescence. It can be used for various applications such as imaging and optical sensors for guest molecules.

Examples of the cage compound (A) of the present invention that satisfies such conditions include, for example, the general formula (Ia):

(In the formula, R ⁴ is the same or different and each is a divalent aromatic hydrocarbon group optionally having a substituent; n is the same or different and each is an integer of 0 or more.)
It is a bivalent group shown by these. ]
(Ia) etc. which are shown by these are mentioned.

This compound has three arches that are uniformly curved by uniformly distorting a plurality of linked rings.

In the general formula (Ia), R ⁴ is the same or different and each is a divalent aromatic hydrocarbon group which may have a substituent. What was mentioned above is employable as a divalent aromatic hydrocarbon group and the substituent which it may have. The preferred specific examples can also be the same. That is, R ⁴ preferably has a bond at the para position, and is a divalent aromatic hydrocarbon group, particularly a phenylene group (especially 1,4-phenylene group) and a naphthylene group (especially 1,4). 5-naphthylene group or 2,6-naphthylene group) and phenylene group (especially 1,4-phenylene group) are preferable, and when having a substituent, a halogen atom, particularly a chlorine atom is preferable as the substituent.

In general formula (Ia), n is the same or different and each is an integer of 0 or more. When both n are 0, they do not have any R ⁴ , that is, R ¹ is a 4,4′-biphenylene group. n is preferably an integer of 0 to 31, more preferably an integer of 0 to 14, still more preferably an integer of 0 to 8, more preferably an integer of 0 to 4, and particularly preferably an integer of 1 to 4.

As preferable R ¹ satisfying such conditions, specifically,

Etc., and one or more of these can be employed.

As the cage compound (A) of the present invention represented by the general formula (Ia) that satisfies the above conditions, specifically,

Etc. are preferable.

The cage compound (A) of the present invention represented by the general formula (Ia) has a substantially spherical nanospace at the center and can incorporate guest molecules therein. For example, in a [6.6.6] cage in which each R ¹ is linked with six 1,4-phenylene groups, the diameter is about 1.84 nm, and each R ¹ has five 1,4-phenylene groups. its diameter at the linked [5.5.5] cage about 1.58 nm, the diameter is in also ^{R 1} is either 1,4 phenylene group linked four [4.4.4] cage about It is 1.30 nm, and R ¹ can be appropriately selected according to the size of the required nanospace.

Such a cage compound of the present invention is a novel compound not described in any literature.

[2] Method for producing cage compound (A) The cage compound (A) of the present invention can be produced, for example, by the following reaction formula 1:

[Wherein R ² will be described later; R ¹ is the same as defined above. ]
Is obtained.

That is, the cage compound (A) of the present invention can be obtained through a conversion step of converting the cyclohexane ring part of the box compound (B) of the present invention into a benzene ring.

For example, a general oxidation reaction can be performed. Specific examples thereof include, for example, a method of heating (acid-treating) the box-shaped compound (B) of the present invention in the presence of an acid, and a reaction with an oxidizing agent in the presence of oxygen (air atmosphere, oxygen atmosphere, etc.). The method etc. to make are also mentioned. As a result, a dehydrogenation reaction or the like is usually applied, and the cyclohexane ring part of the box-shaped compound (B) of the present invention is chemically changed (aromatized) to a benzene ring, whereby the cage-shaped compound (A) of the present invention Can be synthesized. That is, OR ³ (R ³ will be described later) in the cyclohexane ring part of the box-shaped compound (B) of the present invention before conversion is also eliminated, and the dehydrogenation reaction proceeds, whereby the cage-shaped compound of the present invention. (A) is obtained.

R ² will be described later. R ¹ is the same as described above, and preferred specific examples are also the same.

In the case of performing the acid treatment, the specific method thereof is not particularly limited, but for example, the following method is preferable.
(Α) A method in which the box compound (B) of the present invention and an acid are dissolved in a solvent, and then the resulting solution is heated and reacted.
(Β) A method in which the box compound (B) of the present invention is dissolved in a solvent, and then the mixture obtained by mixing the resulting solution and an acid is heated to react.

In addition, when performing the said conversion process, it can also be set as the acid treatment by a non-solvent.

The acid is not particularly limited, but is preferably a strong acid or a salt thereof used for a catalyst or the like. For example, sulfuric acid, sodium hydrogen sulfate, methanesulfonic acid, p-toluenesulfonic acid, tungstophosphoric acid, tungstosilicic acid, molybdophosphoric acid, molybdosilicic acid, boron trifluoride ethylate, tin tetrachloride and the like can be mentioned. These can be used alone or in combination of two or more.

Further, in any of the methods (α) and (β), the amount of the acid used varies depending on the production conditions and the like, but is an excess amount relative to the box-shaped compound (B) of the present invention. Specifically, from the viewpoint of yield, it is preferably 10 to 100 mol, more preferably 20 to 50 mol, per 1 mol of the box-shaped compound (B) of the present invention.

In this conversion step, as described above, not only the box-shaped compound of the present invention is reacted with an acid, but also an oxidizing agent can be used in combination. The oxidizing agent that can be used is not particularly limited, and examples thereof include chloranils such as o-chloranil and p-chloranil; 1,4-benzoquinone, 3,5-di-t-butyl-1,2-benzoquinone, 9, Quinones such as 10-fenvanthrenequinone and 2,3-dichloro-5,6-dicyano-p-benzoquinone; metal oxidizing agents such as CuCl ₂ and K ₂ S ₂ O ₈ can be used. Among these, chloranil is preferable from the viewpoint of yield, and o-chloranil is more preferable.

When an oxidizing agent is used, the amount used is preferably 1 to 10 mol, more preferably 3 to 7 mol, per 1 mol of the box-shaped compound (B) of the present invention, from the viewpoint of yield.

Further, the solvent used in the acid treatment reaction may be a nonpolar solvent or a polar solvent. For example, alkanes such as hexane, heptane, and octane; haloalkanes such as methylene chloride, chloroform, carbon tetrachloride, and ethylene chloride; benzenes such as benzene, toluene, xylene (m-xylene, etc.), mesitylene, and pentamethylbenzene; Halobenzenes such as chlorobenzene and bromobenzene; ethers such as diethyl ether and anisole; dimethyl sulfoxide and the like. The said solvent can be used individually by 1 type or in combination of 2 or more types. In the case of using a solvent, the reaction intermediate from the raw material to the cage compound (A) of the present invention may have low solubility in one solvent used. Alternatively, it may be added in advance or in the middle of the reaction.

The heating temperature in the conversion step is usually preferably 50 ° C. or higher, more preferably 80 ° C. or higher, and more preferably 100 ° C. or higher from the viewpoint of yield, when either method (α) or (β) is adopted. Further preferred is 120 ° C. or higher. Moreover, when using a solvent, it is preferable to set it as the boiling point or less of the said solvent to be used.

The heating means includes an oil bath, an aluminum block thermostatic bath, a heat gun, a burner, and microwave irradiation. In the case of irradiation with microwaves, a known microwave reaction apparatus used for microwave reaction can be used. In heating, reflux cooling may be used in combination.

The reaction atmosphere in the acid treatment is not particularly limited, but is preferably an inert gas atmosphere, and may be an argon gas atmosphere, a nitrogen gas atmosphere, or the like. An air atmosphere can also be used.

Furthermore, in the method for producing a cage compound of the present invention, a purification step can be provided as necessary after the conversion step. That is, it can be subjected to general post-treatment such as solvent (solvent) removal (when a solvent is used), washing, chromatographic separation, and the like. In particular, since the obtained cage compound of the present invention is usually amorphous (non-crystalline) after the conversion step, it can be crystallized by utilizing a conventionally known recrystallization method of an organic compound. In the crystallized product, the organic solvent used in the crystallization operation may be included in the cage constituting the molecule.

The cage compound obtained by the method for producing a cage compound of the present invention is a compound having the properties as described in [1]. According to this production method, a variety of cage compounds such as Compound (Ia) can be synthesized by employing various box compounds as raw materials.

[3] Box-shaped compound The box-shaped compound of the present invention is an intermediate positioned as a starting material for the conversion step in the above-described method for producing a cage compound of the present invention. A box-shaped compound (B) in which rings are connected by a single bond,
The rings are bonded to each other with sp2 hybrid carbon atoms or sp3 hybrid carbon atoms present in the ring,
(1) Formula:

2 to 4 groups represented by
(2) consisting of 6 optionally substituted 1,4-cyclohexylene groups and (3) 0 or more divalent aromatic hydrocarbon groups optionally having substituents A box-shaped compound.

That is, the point having the unit (2) and the number of the units (3) are different from the cage compound of the present invention.

The number of units (1) possessed by the box-shaped compound (B) of the present invention is 2 to 4, preferably 2 or 4, and more preferably 2. When it has two units (1), the box-shaped compound (B) of this invention has three arches which do not have a distortion.

The number of units (2) possessed by the box-type compound (B) of the present invention is six. Thereby, a box-shaped compound is obtained without distortion. And the cage compound of this invention is obtained by using for the above-mentioned conversion process.

As the divalent aromatic hydrocarbon group as the unit (3) that the box-shaped compound (B) of the present invention may have, the same ones as described above can be adopted. The same applies to preferred embodiments. That is, the unit (3) that the box-shaped compound (B) of the present invention may have is a group having a divalent 6-membered aromatic ring or a divalent 6-membered heteroaromatic ring, A group having a bond at the para position is preferred.

Among these, the unit (3) which the box-shaped compound (B) of the present invention may have is preferably a divalent aromatic hydrocarbon group, particularly preferably a phenylene group (especially 1,4-phenylene). Group) and naphthylene group (especially 1,5-naphthylene group or 2,6-naphthylene group), more preferably phenylene group (especially 1,4-phenylene group).

In the box-shaped compound (B) of the present invention, the number of such units (3) is 0 or more, preferably 0 to 92, more preferably 0 to 42, still more preferably 0 to 22, The number is preferably 0 to 12, particularly preferably 0, 6, 9, or 12. That is, the number of units (3) is preferably a multiple of three.

In the box-shaped compound (B) of the present invention, the total number of rings is the total number of units (1) to (3), which is 8 or more, preferably 8 to 100, more preferably 8 to 50. More preferably, it is 8-30, more preferably 8-22, and particularly preferably 8, 14, 17, 20, or 22.

Examples of the box-shaped compound (B) of the present invention that satisfies such conditions include, for example, the general formula (IIa):

(Wherein R ³ is the same or different and each represents a hydrogen atom or a hydroxyl-protecting group; R ⁴ and n are the same as defined above.)
It is a bivalent group shown by these. ]
(IIa) etc. which are shown by these.

Like this general formula (IIa), by having two cyclohexane rings, it can couple | bond with two benzene rings without distortion, As a result, compound (IIa) has three arches .

In the above general formula (IIa-1), R ³ is a hydrogen atom or a hydroxyl-protecting group. The hydroxyl-protecting group is not particularly limited, but is an alkoxyalkyl group (methoxymethyl group (—CH ₂ —O—CH ₃ , hereinafter sometimes referred to as “-MOM”)); alkanoyl Group (eg, acetyl group, propionyl group, etc.); silyl group (eg, trimethylsilyl group, triethylsilyl group, t-butyldimethylsilyl group, etc.); tetrahydropyranyl group (THP); alkyl group (eg, methyl group, ethyl group) Etc.); a benzyl group and the like are mentioned, an alkoxyalkyl group is preferred, and a methoxymethyl group is more preferred.

The above protecting group (particularly an alkoxyalkyl group, especially a methoxymethyl group) is substituted with a hydrogen atom forming an alcohol (hydroxyl group), and functions as an alcohol protecting group.

Among the protecting groups, an alkoxyalkyl group, particularly a methoxymethyl group, can be obtained by reacting chloromethyl methyl ether (Cl—CH ₂ —O—CH ₃ ) with an alcohol that forms a protecting group.

In the general formula (IIa-1), four R ^{3 s} may be the same or different. When the method for producing a cage compound of the present invention is employed, R ³ is preferably an alkoxyalkyl group, particularly a methoxymethyl group.

Specifically, as R ² satisfying such conditions,

[Wherein, MOM is a methoxymethyl group. ]
Etc.

As the box-shaped compound (B) of the present invention represented by the general formula (IIa) that satisfies the above conditions, specifically,

[Wherein, MOM is a methoxymethyl group. ]
Etc.

Such a box-shaped compound of the present invention is a novel compound not described in any literature.

[4] Method for producing box-shaped compound In the present invention, the box-shaped compound is:
General formula (III):

[Wherein R ³ and R ⁴ are the same as described above; m is the same or different and each is an integer of 0 or more; Y is the same or different and each represents a halogen atom or a general formula (III-1):

(Wherein R ⁵ is the same or different and each represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R ⁵ is bonded to each other to form a ring with adjacent —O—B—O—. May be.)
It is group shown by these. ]
It is obtained by a coupling step of coupling the compound (III) represented by Thereafter, the cage compound of the present invention is obtained through the above-described conversion step.

<Compound (III)>
In the compound (III) used as a raw material in the coupling step, R ³ is a hydrogen atom or a hydroxyl-protecting group, and the hydroxyl-protecting group can be the same as described above. Moreover, a preferable specific example can also be made the same. That is, an alkoxyalkyl group is preferable, and a methoxymethyl group is more preferable.

R ⁴ is a divalent aromatic hydrocarbon group which may have a substituent, and can be the same as described above. Moreover, a preferable specific example can also be made the same. That is, R ⁴ preferably has a bond at the para position, and is a divalent aromatic hydrocarbon group, particularly a phenylene group (especially 1,4-phenylene group) and a naphthylene group (especially 1,4). 5-naphthylene group or 2,6-naphthylene group) and phenylene group (especially 1,4-phenylene group) are preferable, and when having a substituent, a halogen atom, particularly a chlorine atom is preferable as the substituent.

M is an integer of 0 or more, and can be the same as above. Moreover, a preferable specific example can also be made the same. That is, an integer of 0 to 16 is preferable, an integer of 0 to 8 is more preferable, an integer of 0 to 5 is more preferable, an integer of 0 to 3 is more preferable, and an integer of 1 to 3 is particularly preferable.

Y is the same or different and each is a halogen atom or general formula (III-1):

(Wherein R ⁵ is the same or different and each represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R ⁵ is bonded to each other to form a ring with adjacent —O—B—O—. May be.)
It is group shown by these.

The halogen atom in Y in the general formula (III) is not limited, and examples thereof include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Of these, a bromine atom is preferable from the viewpoint of yield and the like.

Further, the group represented by the general formula (III-1) may be hereinafter referred to as “boronic acid or an ester group thereof”, and R ⁵ is a hydrogen atom or an alkyl group. The alkyl group has 1 to 10 carbon atoms, preferably 1 to 8 carbon atoms, and more preferably 1 to 5 carbon atoms. Two R ⁵ may be the same or different. When R ⁵ is an alkyl group, the carbon atoms constituting each alkyl group may be bonded to each other to form a ring together with a boron atom and an oxygen atom.

As such boronic acid or its ester group, specifically,

Etc. As a result, when reacting a compound having a terminal boronic acid or its ester group as a compound (III) with a compound having a halogen atom at the terminal, the coupling reaction is more efficient by the Suzuki-Miyaura coupling reaction. Can be advanced.

As the compound (III) satisfying such conditions, specifically,

[Wherein MOM is a methoxymethyl group; B (pin) is

Is]
Etc.

Such compound (III) is a novel compound not described in any literature.

Such compound (III) can be synthesized by various methods. For example, in the case of a compound in which a trifurcated benzene ring and a cyclohexane ring are bonded via another ring,
General formula (IIIa):

[Wherein Y 'is the same or different and each represents a halogen atom or general formula (III-2):

(Wherein R ⁵ is the same as defined above.)
It is. ]
It can be obtained by reacting compound (IIIa) represented by formula (IV) with compound (IV).

However, when the terminal of the compound (IIIa) is a halogen atom, the terminal of the compound (IV) is preferably a boronic acid or an ester group thereof, and conversely, when the terminal of the compound (IIIa) is a boronic acid or an ester group thereof, the compound ( The end of IV) is preferably a halogen atom.

Compound (IV) is a known compound and can be synthesized by a known method. Specifically, for example, the compound (10) described in the pamphlet of WO2011 / 052948 can be used, and can be synthesized according to or according to the synthesis method of the compound (10). In addition, the matter described in the pamphlet of WO2011 / 052948 is cited as a reference in this specification.

Compound (IIIa) and compound (IV) are reacted, and the ratio is preferably from 1 to 100 mol of compound (IV) to 1 mol of compound (IIIa) from the viewpoint of yield and the like. 50 moles are more preferred, and 5 to 20 moles are even more preferred.

The reaction is usually performed in the presence of a catalyst, and a palladium-based catalyst is preferably used. Examples of the palladium-based catalyst include metal palladium and known palladium compounds as catalysts for synthesis of organic compounds (including polymer compounds). In the present invention, a palladium-based catalyst (palladium compound) used in the Suzuki-Miyaura coupling reaction can be used. Specifically, Pd (PPh ₃ ) ₄ (Ph is a phenyl group), PdCl ₂ (PPh ₃ ) ₂ (Ph is a phenyl group), palladium acetate (Pd (OAc) ₂ ), tris (dibenzylideneacetone) dipalladium (0) (Pd ₂ (dba) ₃ ), tris (dibenzylideneacetone) dipalladium (0) chloroform complex, bis (dibenzylideneacetone) palladium (0), bis (trit-butylphosphino) palladium (0) And (1,1′-bis (diphenylphosphino) ferrocene) dichloropalladium (II) and the like. In this step, Pd ₂ (dba) ₃ , Pd (PPh ₃ ) ₄ , (1,1′-bis (diphenylphosphino) ferrocene) dichloropalladium (II) and the like are preferable.

When a palladium catalyst is used in this step, the amount used is usually preferably 0.001 to 1 mol, preferably 0.005 to 0.005 mol per mol of the starting compound (IIIa) from the viewpoint of yield. 1 mole is more preferred.

In addition, some of the palladium-based catalysts described above contain a ligand, but a phosphorus ligand that can be coordinated to a palladium atom can also be used separately from the palladium-based catalyst. Examples of the phosphorus ligand include triphenylphosphine, tri- (o, m, p) -tolylphosphine, tris (2,6-dimethoxyphenyl) phosphine, and tris [2- (diphenylphosphino) ethyl] phosphine. Bis (2-methoxyphenyl) phenylphosphine, 2- (di-t-butylphosphino) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 2- (diphenylphosphino) -2 ′-(N, N-dimethyl) Amino) biphenyl, tri-t-butylphosphine, bis (diphenylphosphino) methane, 1,2-bis (diphenylphosphino) ethane, 1,2-bis (dimethylphosphino) ethane, 1,3-bis (diphenyl) Phosphino) propane, 1,4-bis (diphenylphosphino) butane, 1,5-bis ( Phenylphosphino) pentane, 1,6-bis (diphenylphosphino) hexane, 1,2-bis (dimethylphosphino) ethane, 1,1′-bis (diphenylphosphino) ferrocene (dppf), bis (2- Diphenylphosphinoethyl) phenylphosphine, 2- (dicyclohexylphosphino) -2 ′, 6′-dimethoxy-1,1′-biphenyl (S-Phos), 2- (dicyclohexylphosphino) -2 ′, 4 ′, Examples include 6'-tri-isopropyl-1,1'-biphenyl (X-Phos), bis (2-diphenylphosphinophenyl) ether (DPEPhos), and the like. In this step, 1,1′-bis (diphenylphosphino) ferrocene (dppf) and the like are preferable.

When a phosphorus ligand is used, the amount used is usually preferably 0.001 to 1 mol, preferably 0.005 to 0.1 mol per mol of the starting compound (IIIa) from the viewpoint of yield. Mole is more preferred.

In addition to the above palladium catalyst, a base can be used as necessary. The base is not particularly limited as long as it is a compound that can form an art complex on a boron atom in the Suzuki-Miyaura coupling reaction. Specifically, potassium fluoride, cesium fluoride, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate, potassium carbonate, cesium carbonate, silver carbonate, potassium phosphate, acetic acid Sodium, potassium acetate, calcium acetate, etc. are mentioned. Of these, potassium carbonate is preferred. The amount of the base used is usually preferably about 0.1 to 50 mol, more preferably 0.5 to 20 mol, per 1 mol of the starting compound (IIIa).

The reaction is usually performed in the presence of a reaction solvent. Examples of the reaction solvent include aromatic hydrocarbons such as toluene, xylene and benzene; esters such as methyl acetate, ethyl acetate and butyl acetate; ethers such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diisopropyl ether; Halogenated hydrocarbons such as methyl, chloroform, dichloromethane, dichloroethane, dibromoethane; ketones such as acetone and methyl ethyl ketone; amides such as dimethylformamide and dimethylacetamide; nitriles such as acetonitrile; methanol, ethanol, isopropyl alcohol, and the like Examples of alcohols include dimethyl sulfoxide. These may be used alone or in combination of two or more. Of these, dimethylformamide and the like are preferable in the present invention.

The reaction temperature is usually selected from the range of 0 ° C. or higher and lower than the boiling temperature of the reaction solvent.

The reaction atmosphere is not particularly limited, but is preferably an inert gas atmosphere, and may be an argon gas atmosphere, a nitrogen gas atmosphere, or the like. An air atmosphere can also be used.

In addition, the compound (III) of the present invention is represented by the general formula (V) for the compound (IIIa):

[Wherein, R ³ , R ⁴ , m and X are the same as defined above. ]
It can also be obtained by repeating the protection of the hydroxyl group three times after reacting the compound (V).

The reaction between the compound (IIIa) and the compound (V) is preferably performed in the presence of an organic alkyl metal compound. The organic alkali metal compound is not particularly limited, but an organic lithium compound is preferable, and ethyl lithium, n-propyl lithium, isopropyl lithium, n-butyl lithium, sec-butyl lithium, tert-butyl lithium, pentyl lithium, hexyl lithium, Examples include cyclohexyl lithium and phenyl lithium. Of these, n-butyllithium and the like are preferable.

The amount of the organic alkali metal compound used is preferably 0.8 to 5 mol, more preferably 0.9 to 3.0 mol, per 1 mol of compound (III) for each reaction.

In addition, the reactions are usually performed in the presence of a reaction solvent. Examples of the reaction solvent include aromatic hydrocarbons such as toluene, xylene and benzene; esters such as methyl acetate, ethyl acetate and butyl acetate; ethers such as diethyl ether, tetrahydrofuran, dioxane, dimethoxyethane and diisopropyl ether; Halogenated hydrocarbons such as methyl, chloroform, dichloromethane, dichloroethane, dibromoethane; ketones such as acetone and methyl ethyl ketone; amides such as dimethylformamide and dimethylacetamide; nitriles such as acetonitrile; methanol, ethanol, isopropyl alcohol, and the like Examples of alcohols include dimethyl sulfoxide. These may be used alone or in combination of two or more. Of these, ethers such as diethyl ether are preferred in the present invention.

The reaction temperature is usually selected from the range below the boiling point temperature of the reaction solvent.

Thereafter, the hydroxyl group of the cyclohexane ring is preferably protected by a known method.

Thus, the compound (III) of the present invention can also be obtained by repeating the reaction and the protection three times.

<Coupling process>
In the case of homocoupling, the terminal of compound (III) is preferably a halogen atom.

In the case of homocoupling, the reaction is usually carried out in the presence of a catalyst, and the catalyst is preferably a nickel catalyst.

The nickel catalyst is not particularly limited, but a zero-valent Ni salt or a divalent Ni salt is preferable. These can be used alone or in combination of two or more. These mean both those charged as reagents and those produced in the reaction.

The zero-valent Ni salt is not particularly limited, but bis (1,5-cyclooctadiene) nickel (0) (Ni (cod) ₂ ), bis (triphenylphosphine) nickel dicarbonyl, nickel carbonyl, etc. Is mentioned.

Examples of the divalent Ni salt include nickel acetate (II), nickel trifluoroacetate (II), nickel nitrate (II), nickel chloride (II), nickel bromide (II), nickel (II) acetyl. Acetonate, nickel (II) perchlorate, nickel (II) citrate, nickel (II) oxalate, nickel (II) cyclohexanebutyrate, nickel (II) benzoate, nickel (II) stearate, nickel stearate ( II), nickel sulfamine (II), nickel carbonate (II), nickel thiocyanate (II), nickel trifluoromethanesulfonate (II), bis (1,5-cyclooctadiene) nickel (II), bis (4- Diethylaminodithiobenzyl) nickel (II), nickel cyanide (II), fluoride Neckel (II), nickel boride (II), nickel borate (II), nickel (II) hypophosphite, nickel sulfate (II) sulfate, nickel (II) hydroxide, cyclopentadienyl nickel (II), And hydrates thereof, and mixtures thereof.

As the zero-valent Ni salt and the divalent Ni salt, a compound in which a ligand is coordinated in advance may be used.

The amount of the nickel catalyst used is usually 0.01 to 50 mol, preferably 0.1 to 10 mol, more preferably 0.1 to 10 mol, based on 1 mol of the starting compound (III). The amount is 0.5 to 5 mol, particularly preferably 1 to 3 mol.

In the production method of the present invention, a ligand capable of coordinating to nickel (nickel atom) can be used together with the nickel catalyst. Examples of the ligand include carboxylic acid, amide, phosphine, oxime, sulfonic acid, 1,3-diketone, Schiff base, oxazoline, diamine, carbon monoxide, and carbene. And a ligand. These can be used alone or in combination of two or more. Coordination atoms in the above ligand are a nitrogen atom, a phosphorus atom, an oxygen atom, a sulfur atom, etc., and these ligands include a monodentate ligand having only one coordination atom and a polydentate having two or more. There are bidentate ligands. In addition, carbon monoxide and carbene are ligands having a carbon atom as a coordination atom. Any known or commercially available ligand can be used.

When the above ligand is used, the amount used is usually 0.01 to 50 mol, preferably 0.1 to 10 mol, more preferably 0.5 mol, relative to 1 mol of the starting compound (III). -5 mol, particularly preferably 1-3 mol.

The reaction is usually performed in the presence of a reaction solvent. Examples of the reaction solvent include aliphatic hydrocarbons (hexane, cyclohexane, heptane, etc.), aliphatic halogenated hydrocarbons (dichloromethane, chloroform, carbon tetrachloride, dichloroethane, etc.), aromatic hydrocarbons (benzene, toluene, Xylene, chlorobenzene, etc.), ethers (diethyl ether, dibutyl ether, dimethoxyethane (DME), cyclopentyl methyl ether (CPME), tert-butyl methyl ether, tetrahydrofuran, dioxane, etc.), esters (ethyl acetate, ethyl propionate, etc.) ), Acid amides (dimethylformamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone (1-methyl-2-pyrrolidinone) (NMP), nitriles (acetonitrile, propionitrile, etc.), dimethyl Sulfoxide (DMSO) and the like. They may be used in combination of at least one kind alone or two kinds.

In the case of cross-coupling , the compound (III) whose terminal is a halogen atom is preferably reacted with the compound (III) whose terminal is a boronic acid or an ester group thereof.

In the case of cross-coupling, the compound (III) and the compound (IV) are reacted, but the ratio is 0.8 to 5.0 mol with respect to 1 mol with respect to one mol from the viewpoint of yield and the like. Is preferable, and 0.9 to 3.0 mol is more preferable.

The reaction is usually performed in the presence of a catalyst, and preferably a palladium-based catalyst is used. What has been described above can be used. In this step, palladium acetate or the like is preferable.

When a palladium-based catalyst is used in this step, the amount used thereof is usually preferably 0.01 to 1 mol with respect to 1 mol of any compound (III) as a raw material from the viewpoint of yield, and 0.05 More preferred is ˜0.5 mol.

Similarly, phosphorus ligands can also be used. As the phosphorus ligand, those described above can be used. In this step, 2- (dicyclohexylphosphino) -2 ′, 6′-dimethoxy-1,1′-biphenyl (S-Phos) and the like are used. preferable.

When a phosphorus ligand is used, the amount used is preferably 0.01 to 2 mol, preferably 0.05 to 1.0 mol, relative to 1 mol of the starting compound (III) from the viewpoint of yield. Mole is more preferred.

Similarly, in addition to the palladium catalyst, a base can be used as necessary. As the base, those described above can be used, and sodium hydroxide is preferable. The amount of the base used is usually preferably about 0.1 to 50 mol, more preferably 0.5 to 20 mol, relative to 1 mol of the starting compound (III).

The reaction is usually performed in the presence of a reaction solvent. As the reaction solvent, those usable in the synthesis method of compound (III) can be used as they are, but dioxane, toluene and the like are preferable.

Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to these examples.

Unless otherwise noted, all materials including dry solvents (dimethylformamide (DMF) and dimethyl sulfoxide (DMSO)) were obtained from commercial suppliers and used without further purification. However, tetrahydrofuran (THF), dichloromethane, and m-xylene were purified by filtration through a solvent purification system (glass outline). All reactions were performed using standard vacuum lines and Schlenk techniques. Work-up and purification procedures were performed in air using reagent grade solvents. 1,3,5-tris (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzene and cis-1,4-bis (4-phenyl) -1-2, 4-Bis (methoxymethyl) cyclohexane has been reported previously (Liu, Y .; Niu, F .; Lian, J .; Zheg, P .; Niu, H. Synth. Mat. 2010, 160, 2055. and Omachi, H. Matsuura, S .; Segawa, Y .; Itami, K. Angew. Chem. Int. Ed. 2010, 49, 10202.).

Thin layer chromatography (TLC) was performed using E. Merck silica gel 60 F254 precoated plates (0.25 mm). The chromatogram was analyzed with a UV lamp (254 nm). Flash column chromatography was performed using E. Merck silica gel 60 (230-400 mesh). Preparative thin layer chromatography (PTLC) was performed using Wako Gel (registered trademark) B5-F silica-coated plate (0.75 mm). Recycle preparative gel permeation chromatography (GPC) was performed using a JAI LC-9204 measuring instrument equipped with JAIGEL-1H / JAIGEL-2H rows using chloroform as the eluent. High resolution mass spectrum (HRMS) using 9-nitroanthracene as matrix, JEOL JMS700 (fast atom bombardment mass spectrometry, FAB-MS) or Bruker Daltonics Ultraflex III TOF / TOF (MALDI-TOF-MS) Obtained from. Melting points were measured with an MPA100 Optimelt automatic melting point system. Nuclear magnetic resonance (NMR) spectra were recorded on a JEOL JNM-ECA-600 ( ¹ H 600 MHz, ¹³ C 150 MHz) spectrometer. ¹ H NMR chemical shifts were expressed as relative parts per million (ppm) of CHCl ₃ (δ 7.26 ppm). ¹³ C NMR chemical shifts were expressed in relative parts per million (ppm) of CDCl ₃ (δ 77.0 ppm).

Synthesis Example 1: Synthesis of 1,3,5-tris (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzene

[Wherein Ph is a phenyl group; KOAc is potassium acetate; DMF is dimethylformamide; dppf is 1,1′-bis (diphenylphosphino) ferrocene; DMSO is dimethyl sulfoxide; B (pin) is 4, 4, 5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl. ]
According to the above reaction formula, 1,3,5-tris (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzene was synthesized by a conventional method (Condition 1:83). %, Condition 2: 78%).

Example 1-1 Tridentate Compound (Part 1)

To a 500 mL round bottom flask with a magnetic stir bar, add 1,3,5-tris (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzene (2) (1.82 g, 3.99 mmol), cis-1,4-bis (4-bromophenyl) -1,4-bis (methoxymethoxy) cyclohexane (3) (20.6 g, 40.1 mmol), PdCl ₂ (dppf) · CH ₂ Cl ₂ (dppf is 1,1′-bis (diphenylphosphino) ferrocene) (32.2 mg, 39.4 μmol), and K ₂ CO ₃ (5.53 g, 40.0 mmol) are added, and the flask is evacuated and filled with argon. Repeated times. Next, dry dimethylformamide (DMF) (200 mL) was added to the flask. The reaction mixture was stirred at 90 ° C. for 24 hours. After cooling to room temperature, the mixture was extracted with ethyl acetate (EtOAc), washed with brine, dried over Na ₂ SO ₄ and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane / EtOAc = 5: 1 to 1: 1) to obtain the target three-mut compound (4) as a white solid (2.91 g, 53%).
¹ H NMR (600 MHz, CDCl ₃ ) δ 2.10 (brs, 12H), 2.35 (brs, 12H), 3.41 (s, 9H), 3.43 (s, 9H), 4.44 (s, 6H), 4.48 (s, 6H), 7.33 (d, J = 8.6 Hz, 6H), 7.45 (d, J = 8.6 Hz, 6H), 7.52 (d, J = 8.1 Hz, 6H), 7.63 (d, J = 8.1 Hz, 6H) , 7.73 (s, 3H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 32.9 (CH ₂ ), 56.0 (CH ₃ ), 77.8 (4 °), 78.0 (4 °), 92.1 (CH ₂ ), 92.2 (CH ₂ ), 121.6 (4 °), 125.0 (CH), 127.2 (CH), 127.3 (CH), 128.7 (CH), 131.5 (CH), 140.2 (4 °), 141.7 (4 °); HRMS ( FAB) m / z calcd for C ₇₂ H ₈₁ Br ₃ O ₁₂ Na [M + Na] ⁺ : 1397.3170, found 1397.3158; mp: 103.4-120.0 ° C.

The reaction proceeded in the same manner when each component was changed as follows.

Synthesis Example 2: Synthesis of 4- (4-chlorophenyl) -4-hydroxycyclohexanone

[Wherein n-BuLi is n-butyllithium; THF is tetrahydrofuran. ]
To a 500 mL round bottom flask containing a magnetic stir bar, 1-bromo-4-chlorobenzene (31.6 g, 165 mmol) was added and dry tetrahydrofuran (THF) (250 mL, 600 mM) was added. A solution of n-butyllithium in hexane (103 mL, 1.6 M, 165 mmol) was added at −78 ° C. over 30 minutes. After stirring at -78 ° C for 1 hour, 1,4-cyclohexanedione monoethylene ketal (23.4 g, 150 mmol) was added as a solid, and the mixture was further stirred at -78 ° C for 1 hour to obtain intermediate compound (25). . After warming to room temperature, 3M hydrochloric acid solution (100 mL) was added and stirred for 1 day. The mixture was neutralized with saturated aqueous NaHCO ₃ solution, extracted with ethyl acetate (EtOAc), washed with brine, dried over Na ₂ SO ₄ and concentrated in vacuo. The crude product was obtained and purified by recrystallization (CHCl ₃ ) three times to give 4- (4-chlorophenyl) -4-hydroxycyclohexanone (26) as a white solid (29.9 g, 89%).
Data for Compound 25:
¹ H NMR (600 MHz, CDCl ₃ ) δ 1.58 (s, 1H), 1.67-1.72 (m, 2H), 1.76-1.81 (m, 2H), 2.04-2.18 (m, 4H), 3.95-4.02 (m , 4H), 7.30 (d, 8.4 Hz, 2H), 7.45 (d, 8.4 Hz, 2H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 30.7 (CH ₂ ), 36.6 (CH ₂ ), 64.2 (CH ₂ ), 64.4 (CH ₂ ), 72.2 (4 °), 108.2 (4 °), 126.1 (CH), 128.3 (CH), 132.7 (4 °), 147.0 (4 °); mp: 153.3-155.2 ° C.
Data for Compound 26:
¹ H NMR (600 MHz, CDCl ₃ ) δ 2.03 (s, 1H), 2.11-2.19 (m, 2H), 2.20-2.29 (m, 2H), 2.31-2.39 (m, 2H), 2.85-2.95 (m , 2H), 7.34 (d, 9.0 Hz, 2H), 7.45 (d, 8.4 Hz, 2H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 37.2 (CH ₂ ), 38.5 (CH ₂ ), 71.8 (4 °), 125.9 (CH), 128.6 (CH), 133.3 (4 °), 145.6 (4 °), 211.2 (4 °); HRMS (FAB) m / z calcd for C ₁₂ H ₁₂ ClO ₂ [MH] ^- : 223.0526, found; 223.0530; mp: 139.7-140.5 ° C.

Synthesis Example 3: Synthesis of 4-chlorophenyl-4-methoxymethoxycyclohexanone

[Wherein i-Pr ₂ NEt is diisopropylethylamine; MOM is a methoxymethyl group. ]
In a 200 mL round bottom flask containing a magnetic stir bar, 4- (4-chlorophenyl) -4-hydroxycyclohexanone (26) (15.7 g, 69.9 mmol) obtained in Synthesis Example 2 and dry CH ₂ Cl ₂ (70 mL, 1 M), diisopropylethylamine (24.4 mL, 140 mmol), chloromethyl methyl ether (10.6 mL, 140 mmol) were added. The mixture was stirred for 48 hours at room temperature, then quenched with saturated aqueous NH ₄ Cl, extracted with CH ₂ Cl ₂ , dried over Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by column chromatography (hexane / ethyl acetate (EtOAc) = 10: 1 to 5: 1) to give 4- (4-chlorophenyl) -4-methoxymethoxycyclohexanone (27) as a white solid. (16.1 g, 85%). Cis and trans isotopes were identified by ¹ H NMR spectrum.
¹ H NMR (600 MHz, CDCl ₃ ) δ 2.12-2.20 (m, 2H), 2.32-2.38 (m, 2H), 2.39-2.46 (m, 2H), 2.86-2.95 (m, 2H), 3.43 (s , 3H), 4.52 (s, 2H), 7.35 (d, 9.0 Hz, 2H), 7.40 (d, 9.0 Hz, 2H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 36.3 (CH ₂ ), 37.2 ( CH ₂ ), 56.6 (CH ₃ ), 92.9 (CH ₂ ), 127.4 (CH), 128.7 (CH), 133.7 (4 °), 142.3 (4 °), 211.0 (4 °); HRMS (FAB) m / z calcd for C ₁₄ H ₁₇ ClO ₃ Na [M + Na] ⁺ : 291.0764, found; 291.0768; mp: 66.2-67.8 ° C.

Synthesis Example 4: Synthesis of monosubstituted tribromobenzene

[Wherein MOM, n-BuLi and i-Pr ₂ MEt are the same as above; Et ₂ O is diethyl ether. ]
To a 500 mL round bottom flask containing a magnetic stir bar, 1,3,5-tribromobenzene (7.87 g, 25.0 mmol) and dry diethyl ether (Et ₂ O) (200 mL, 75 mM) were added. To this mixture was added n-butyllithium in hexane (15.6 mL, 1.6 M, 25.0 mmol) at -78 ° C. After stirring at −78 ° C. for 1 hour, 4-chlorophenyl-4-methoxymethoxycyclohexanone (27) (7.15 g, 26.6 mmol) obtained in Synthesis Example 3 in diethyl ether (Et ₂ O) (25 mL) was added. The resulting mixture was further stirred at −78 ° C. for 1 hour. The mixture was allowed to warm to room temperature and then quenched with saturated aqueous NH ₄ Cl, extracted with CH ₂ Cl ₂ , dried over Na ₂ SO ₄ and concentrated in vacuo to give intermediate compound (28) as a mixture.

In a 100 mL round bottom flask containing a magnetic stir bar, a mixture containing the intermediate compound (28), dry CH ₂ Cl ₂ (50 mL, 500 mM), diisopropylethylamine (17.4 mL, 100 mmol), and chloromethylmethyl Ether (7.6 mL, 100 mmol) was added. The mixture was stirred at room temperature for 48 hours before being quenched with saturated aqueous NH ₄ Cl, extracted with CH ₂ Cl ₂ , dried over Na ₂ SO ₄ and concentrated in vacuo. The crude product was purified by column chromatography (hexane / ethyl acetate (EtOAc) = 10: 1 to 8: 1) to give the monosubstituted tribromobenzene (29) as a white solid (8.64 g, 2 steps) 63%). The desired trans isomer was also obtained in 28% yield. Cis and trans isotopes were identified by ¹ H NMR spectrum.
Compound 28 data
¹ H NMR (600 MHz, CDCl ₃ ) δ 1.75-2.03 (m, 5H, include OH), 2.18-2.41 (m, 4H), 3.34 (s, 3H), 4.37 (s, 2H), 7.38 (d, 9.0 Hz, 2H), 7.44 (d, 8.4 Hz, 2H), 7.45 (s, 2H), 7.54 (s, 1H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 32.5 (CH ₂ ), 35.4 (CH ₂ ), 55.9 (CH ₃ ), 72.1 (4 °), 77.7 (4 °), 92.0 (CH ₂ ), 123.1 (4 °), 127.1 (CH), 128.7 (CH), 128.8 (CH), 132.8 ( CH), 133.9 (4 °), 139.3 (4 °), 151.0 (4 °); HRMS (FAB) m / z calcd for C ₂₀ H ₂₀ Br ₂ ClO ₃ [MH] ^- : 502.9447, found; 502.9444; mp : 158.0-159.2 ℃.
Compound 29 data
¹ H NMR (600 MHz, CDCl ₃ ) δ 1.71-2.45 (m, 8H), 3.37 (s, 3H), 3.41 (s, 3H), 4.39 (s, 2H), 4.44 (s, 2H), 7.32 ( d, 8.4 Hz, 2H), 7.39 (d, 8.4 Hz, 2H), 7.47 (s, 2H), 7.56 (s, 1H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 32.6 (CH ₂ ), 32.9 (CH ₂ ), 55.9 (CH ₃ ), 56.2 (CH ₃ ), 77.4 (4 °), 77.6 (4 °), 92.1 (CH ₂ ), 92.3 (CH ₂ ), 123.1 (4 °), 128.4 (CH ), 128.7 (CH), 133.3 (CH), 133.7 (4 °); HRMS (FAB) m / z calcd for C ₂₂ H ₂₅ Br ₂ ClO ₄ Na [M + Na] ⁺ : 568.9706, found; 568.9703; mp : 77.0-80.6 ℃.

Synthesis Example 5 Synthesis of disubstituted tribromobenzene (Part 1)

[Wherein, MOM, n-BuLi and Et ₂ O are the same as above. ]
Similarly to Synthesis Example 4, the monosubstituted tribromobenzene (29) (8.23 g, 15.0 mmol) obtained in Synthesis Example 4 and 4- (4-chlorophenyl) -4-hydroxycyclohexanone obtained in Synthesis Example 2 (26) (4.43 g, 16.5 mmol) was reacted to give the tribromobenzene disubstituted product (30) as a white solid (6.77 g, 61%).
¹ H NMR (600 MHz, CD ₂ Cl ₂ ) δ 1.62-2.28 (m, 16H), 2.37 (s, 1H), 3.20 (s, 3H), 3.21 (s, 3H), 3.35 (s, 3H), 4.26 (s, 2H), 4.275 (s, 2H), 4.284 (s, 2H), 7.21 (d, 9.0 Hz, 2H), 7.25 (d, 9.0 Hz, 4H), 7.28 (d, 8.4 Hz, 4H) , 7.31-7.37 (m, 5H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 33.0 (CH ₂ ), 33.1 (CH ₂ ), 33.2 (CH ₂ ), 35.8 (CH ₂ ), 55.9 (CH ₃ ) , 56.0 (CH ₃ ), 56.1 (CH ₃ ), 72.3 (4 °), 77.8 (4 °), 78.1 (4 °), 92.2 (CH ₂ ), 92.26 (CH ₂ ), 92.28 (CH ₂ ), 122.8 (4 °), 122.9 (CH), 127.8 (CH), 128.7 (CH), 128.8 (CH), 129.2 (CH), 133.6 (4 °), 133.8 (4 °), 140.4 (4 °), 141.4 ( 4 °), 145.8 (4 °), 150.0 (4 °); HRMS (FAB) m / z calcd for C ₃₆ H ₄₃ BrCl ₂ O ₇ Na [M + Na] ⁺ : 759.1467, found; 759.1474.

Also, when the solvent was changed to tetrahydrofuran, the reaction proceeded similarly (18%).

Synthesis Example 6: Synthesis of disubstituted product of tribromobenzene (part 2)

[Wherein, MOM and i-Pr ₂ NEt are the same as above. ]
In the same manner as in Synthetic Example 4, protection was performed using the disubstituted bromobenzene (30) (6.65 g, 9.00 mmol) obtained in Synthetic Example 5 (dry CH ₂ Cl ₂ : 333 mM, diisopropylethylamine: 60 mmol). , Chloromethyl methyl ether: 60 mmol), and the protected tribromobenzene disubstituted product (31) was obtained as a white solid (6.56 g, 93%).
¹ H NMR (600 MHz, CDCl ₃ ) δ 1.59-2.50 (m, 16H), 3.34 (s, 6H), 3.36 (s, 6H), 4.36 (s, 4H), 4.38 (s, 4H), 7.28 ( d, 8.4 Hz, 2H), 7.34 (d, 8.4 Hz, 2H), 7.40 (s, 2H), 7.46 (s, 1H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 32.7 (CH ₂ ), 32.9 (CH ₂ ), 55.9 (CH ₃ ), 56.0 (CH ₃ ), 77.6 (4 °), 77.7 (4 °), 92.00 (CH ₂ ), 92.03 (CH ₂ ), 122.8 (4 °), 124.1 (CH ), 128.2 (CH), 128.5 (CH), 129.0 (CH), 133.5 (4 °), 140.5 (4 °), 145.3 (4 °); HRMS (FAB) m / z calcd for C ₃₈ H ₄₇ BrCl ₂ O ₈ Na [M + Na] ⁺ : 805.1710, found; 805.1698; mp: 129.8-132.5 ° C.

Example 1-2: Synthesis of trisubstituted product of tribromobenzene (Part 1)

[Wherein, MOM, n-BuLi, Et ₂ O and THF are the same as above. ]
In the same manner as in Synthesis Examples 4 and 5, the protected trisubstituted bromobenzene (31) obtained in Synthesis Example 6 (31) (6.26 g, 8.00 mmol) and 4- (4-chlorophenyl) obtained in Synthesis Example 1 were used. -4-hydroxycyclohexanone (27) (2.29 g, 8.52 mmol) was reacted in a mixed solvent of diethyl ether (Et ₂ O): tetrahydrofuran (THF) = 2: 1 (total solvent: 50 mM, n− Butyllithium: 8.00 mmol), tribromobenzene trisubstituted product (32) was obtained as a white solid (5.62 g, 72%).
¹ H NMR (600 MHz, CD ₂ Cl ₂ ) δ 1.53-2.34 (m, 25H, include OH), 3.16 (s, 6H), 3.21 (s, 3H), 3.35 (s, 6H), 4.20 (s, 4H), 4.28 (s, 2H), 4.29 (s, 4H), 7.13-7.36 (m, 15H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 33.2 (CH ₂ ), 35.9 (CH ₂ ), 56.0 (CH ₃ ), 56.1 (CH ₃ ), 72.7 (4 °), 77.9 (4 °), 78.1 (4 °), 78.4 (4 °), 92.2 (CH ₂ ), 92.3 (CH ₂ ), 123.1 (CH ), 124.7 (CH), 128.66 (CH), 128.72 (CH), 129.0 (CH), 133.5 (4 °), 133.6 (4 °), 140.8 (4 °), 141.8 (4 °), 143.0 (4 ° ), 147.2 (4 °); HRMS (FAB) m / z calcd for C ₅₂ H ₆₅ Cl ₃ O ₁₁ Na [M + Na] ⁺ : 995.3476, found; 995.3488.

When the solvent was tetrahydrofuran alone, the reaction proceeded in the same manner (21%).

Example 1-3: Synthesis of trisubstituted product of tribromobenzene (Part 2)

[Wherein, MOM and i-Pr ₂ NEt are the same as above. ]
In the same manner as in Synthesis Examples 4 and 6, the trisubstituted benzene (32) (5.35 g, 5.50 mmol) obtained in Example 1-2 was used for protection (dry CH ₂ Cl ₂ : 250 mM, diisopropyl). Ethylamine: 22.0 mmol, chloromethyl methyl ether: 22.0 mmol), and a trisubstituted benzene (33) of protected tribromobenzene was obtained as a white solid (5.23 g, 94%).
¹ H NMR (600 MHz, CD ₂ Cl ₂ ) δ 1.60-2.32 (br, 24H), 3.14 (s, 9H), 3.25 (s, 9H), 4.20 (s, 6H), 4.29 (s, 6H), 7.16 (d, 8.4 Hz, 6H), 7.21 (d, 7.2 Hz, 6H), 7.32 (s, 3H); ¹³ C NMR (150 MHz, CD ₂ Cl ₂ ) δ 33.26 (CH ₂ ), 33.32 (CH ₂ ), 56.0 (CH ₃ ), 56.1 (CH ₃ ), 77.9 (4 °), 78.4 (4 °), 92.2 (CH ₂ ), 92.4 (CH ₂ ), 125.1 (CH), 128.7 (CH), 133.5 ( 4 °), 142.1 (4 °), 142.7 (4 °); HRMS (FAB) m / z calcd for C ₅₄ H ₆₉ Cl ₃ O ₁₂ Na [M + Na] ⁺ : 1037.3752, found; 1037.3751; mp: 115.8 -117.2 ° C.

Example 1-4: Synthesis of trisubstituted product of tribromobenzene (Part 3)

[Wherein, MOM, B (pin) and KOAc are the same as above; dba is dibenzylideneacetone; X-Phos is 2- (dicyclohexylphosphino) -2 ′, 4 ′, 6′-tri-isopropyl-1, 1'-biphenyl. ]
To a 100 mL Schlenk tube containing a magnetic stirrer, the trisubstituted benzene (33) (4.08 g, 4.01 mmol) protected in Example 1-3, bis (pinacolato) diboron (3.70 g, 14.6 mmol), Pd ₂ (dba) ₃ · CHCl ₃ (dba is dibenzylideneacetone) (62.1 mg, 60.0 μmol), 2- (dicyclohexylphosphino) -2 ′, 4 ′, 6′-tri-isopropyl-1 1,1′-biphenyl (X-Phos) (144.3 mg, 303 μmol) and potassium acetate (KOAc) (3.54 g, 36.1 μmol) were added, and the flask was evacuated and filled with nitrogen three times. Next, dry dioxane (40 mL) was added to the flask. The reaction mixture was stirred at 110 ° C. for 16 hours. The mixture was cooled to room temperature, extracted with ethyl acetate (EtOAc), washed with brine, dried over Na ₂ SO ₄ and concentrated under reduced pressure. The crude product was purified by GPC to give the boronated tribromobenzene trisubstituted product (34) (4.81 g, 93%) as a white solid.
¹ H NMR (600 MHz, CDCl ₃ ) δ 1.33 (s, 36H), 1.73-2.45 (br, 24H), 3.25 (s, 9H), 3.37 (s, 9H), 4.27 (s, 6H), 4.38 ( s, 6H), 7.36 (s, 3H), 7.39 (d, 7.2 Hz, 6H), 7.75 (d, 8.4 Hz, 6H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 24.8 (CH ₃ ), 32.7 (CH ₂ ), 33.0 (CH ₂ ), 55.9 (CH ₃ ), 78.1 (4 °), 78.2 (4 °), 83.7 (4 °), 91.9 (CH ₂ ), 92.1 (CH ₂ ), 124.4 (4 °), 126.1 (CH), 128.2 (4 °), 134.8 (CH); HRMS (FAB) m / z calcd for C ₇₂ H ₁₀₅ B ₃ O ₁₈ Na [M + Na] ⁺ : 1313.7509, found; 1313.7521.

Example 1-5: Synthesis of trisubstituted product of tribromobenzene (Part 4)

[Wherein, MOM and B (pin) are the same as above. ]
To a 50 mL Schlenk tube containing a magnetic stirrer was added the boronated tribromobenzene tri-substituted product (34) (642 mg, 497 μmol) obtained in Example 1-4, and then 1,4-dibromobenzene. (1.08 g, 4.58 mmol), PdCl ₂ (dppf) (dppf is 1,1′-bis (diphenylphosphino) ferrocene) (36.3 mg, 44.5 μmol), K ₂ CO ₃ (432 mg, 3.13 mmol), and Ag ₂ O (349 mg, 1.51 mmol) was added and the flask was evacuated and filled with nitrogen three times. Next, dry tetrahydrofuran (THF) (22 mL) and degassed water (2 mL) were added to the flask. The reaction mixture was stirred at 60 ° C. for 36 hours. The mixture was cooled to room temperature, extracted with ethyl acetate (EtOAc), washed with brine, dried over Na ₂ SO ₄ and concentrated under reduced pressure. The crude product was purified by GPC to obtain the target compound (35) as a white solid (391 mg, 57%).
¹ H NMR (600 MHz, CDCl ₃ ) δ 1.75-2.61 (br, 14H), 3.28 (s, 9H), 3.41 (s, 9H), 4.33 (s, 6H), 4.44 (s, 6H), 7.33 ( d, 8.4 Hz, 6H), 7.40 (s, 15H), 7.50 (d, 8.4 Hz, 6H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 32.9 (CH ₂ ), 33.0 (CH ₂ ), 55.8 ( CH ₃ ), 56.0 (CH ₃ ), 78 (4 °), 78 (4 °), 91.8 (CH ₂ ), 92.2 (CH ₂ ), 121.6 (4 °), 124.7 (4 °), 126.7 (CH) , 127.1 (CH), 128.4 (CH), 131.8 (CH), 138.9 (4 °), 139.1 (4 °), 142.1 (4 °); HRMS (FAB) m / z calcd for C ₇₂ H ₈₁ Br ₃ O ₁₂ Na [M + Na] ⁺ : 1401.3158, found; 1401.3131; mp: 177.1-179.3 ° C.

Example 2-1: Synthesis of Box-shaped Compound (Part 1)

[Wherein, MOM is the same as above. ]
In a 100 mL round bottom flask equipped with a magnetic stir bar, the trifurcated compound (4) obtained in Example 1-1 (139 mg, 101 μmol), Ni (cod) ₂ (cod is 1,5-cyclooctadiene) (91.1 mg, 331 μmol) and 2,2′-bipyridyl (52.6 mg, 337 μmol) were added. Next, dry dimethylformamide (DMF) (50 mL, 2 mM) was added to the flask. The reaction mixture was stirred at 90 ° C. for 24 hours. After cooling to room temperature, the mixture was extracted with ethyl acetate (EtOAc), washed with brine, dried over Na ₂ SO ₄ and concentrated under reduced pressure. The crude product was purified by GPC and PTLC (CHCl ₃ ) to give the [6.6.6] cage precursor box compound (5) as a white solid (13.6 mg, 12%).
¹ H NMR (600 MHz, CDCl ₃ , 50 ° C) δ 2.13 (brs, 12H), 2.20 (brs, 12H), 2.35-2.48 (m, 24H), 3.41 (s, 18H), 3.43 (s, 18H) , 4.47 (s, 24H), 7.48 (d, J = 8.4 Hz, 24H), 7.51 (d, J = 8.4 Hz, 12H), 7.55 (d, J = 8.4 Hz, 12H), 7.63 (d, J = 8.4 Hz, 12H), 7.76 (s, 6H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 32.8 (CH ₂ ), 56.0 (CH ₃ ), 56.1 (CH ₃ ), 78.0 (4 °), 92.17 ( CH ₂ ), 92.24 (CH ₂ ), 124.7 (CH), 126.8 (CH), 127.0 (CH), 127.2 (CH), 127.5 (CH), 139.6 (4 °), 139.9 (4 °), 141.5 (4 °); HRMS (FAB) m / z calcd for C ₁₄₄ H ₁₆₂ O ₂₄ Na [M + Na] ⁺ : 2298.1348, found 2298.1353; mp: partially decomposed at 300 ° C.

Example 2-2: Synthesis of box-shaped compound (2)

[Wherein, MOM is the same as above. ]
To a 50 mL Schlenk tube containing a magnetic stirrer, the trisubstituted bromobenzene compound obtained in Example 1-3 (33) (103 mg, 101 μmol), bis (1,5-cyclooctadiene) nickel (0 ) (Ni (cod) ₂ ) (83.4 mg, 303 μmol) and 1,10-phenanthroline (phen) (55.8 mg, 310 μmol) were added. Next, dry tetrahydrofuran (THF) (25 mL) was added to the flask. The reaction mixture was stirred under reflux for 40 hours. After cooling to room temperature, the mixture was filtered through a short pad of celite (EtOAc) and concentrated in vacuo. The crude product was purified by GPC and PTLC (ethyl acetate (EtOAc)) to give the [4,4,4] cage precursor box compound (36) as a white solid (8.1 mg, 8%).
¹ H NMR (600 MHz, CDCl ₃ ) δ 1.28-1.50 (br, 12H), 2.06 (d, 12.0 Hz, 12H), 2.43 (td, 12.0 Hz, 2.4 Hz, 12H), 2.52-2.66 (br, 12H ), 3.28 (s, 18H), 3.48 (s, 18H), 4.46 (s, 12H), 4.49 (s, 12H), 6.92 (br, 12H), 7.02 (br, 12H), 7.77 (s, 6H) ; ¹³ C NMR (150 MHz, CDCl ₃ ) δ 32.2 (CH ₂ ), 34.2 (CH ₂ ), 55.4 (CH ₃ ), 56.5 (CH ₃ ), 77.8 (4 °), 78.5 (4 °), 91.3 ( CH ₂ ), 92.6 (CH ₂ ), 125.6 (CH), 126.5 (CH), 127.5 (CH), 138.6 (4 °), 128.8 (4 °), 144.1 (4 °); HRMS (FAB) m / z calcd for C ₁₀₈ H ₁₃₈ O ₂₄ Na [M + Na] ⁺ : 1842.9509, found 1842.9461; mp: 237.3 ° C.

Example 2-3: Synthesis of Box-shaped Compound (Part 3)

[Wherein, MOM and B (pin) are the same as above; Pd (OAc) ₂ is palladium (II) acetate; S-Phos is 2- (dicyclohexylphosphino) -2 ′, 6′-dimethoxy-1,1 '-Biphenyl. ]
In a 100 mL round-bottom flask containing a magnetic stir bar, trisubstituted bromobenzene (33) (104 mg, 102 μmol) obtained in Example 1-3 and boronated tribromo obtained in Example 1-4 were obtained. Benzene tri-substituted product (34) (157 mg, 122 μmol), palladium (II) acetate (Pd (OAc) ₂ ) (2.4 mg, 11 μmol), 2- (dicyclohexylphosphino) -2 ′, 6′-dimethoxy- 1,1′-biphenyl (S-Phos) (8.8 mg, 21 μmol) and K ₃ PO ₄ (209 mg, 985 μmol) were added, and the flask was evacuated and filled with nitrogen three times. Next, dry dioxane (47 mL) and degassed water (3 mL) were added to the flask. The reaction mixture was stirred at 100 ° C. for 40 hours. The mixture was cooled to room temperature, extracted with ethyl acetate (EtOAc), washed with brine, dried over Na ₂ SO ₄ and concentrated under reduced pressure. The crude product was purified by GPC and PTLC to give the [4,4,4] cage precursor box compound (36) as a white solid (13.7 mg, 7%).

Example 2-4: Synthesis of Box-shaped Compound (Part 4)

[Wherein, MOM and B (pin) are the same as above. ]
Similar to Example 2-3, the boronated tribromobenzene tri-substituted product (34) (139 mg, 101 μmol) obtained in Example 1-4 and the tribromobenzene obtained in Example 1-5 were mixed. Trisubstituted product (35) (159 mg, 123 μmol) was used as a catalyst with PdCl ₂ (dppf) .CH ₂ Cl ₂ (dppf is 1,1′-bis (diphenylphosphino) ferrocene) (7.7 mg, 9.4 mg). μmol), K ₂ CO ₃ (85.4 mg, 618 μmol), dry toluene (45 mL) and degassed water (5 mL) in the presence of 40 hours at 80 ° C. to give a [5,5,5] cage precursor A box compound (37) was obtained as a white solid (22.5 mg, 11%).
¹ H NMR (600 MHz, CDCl ₃ ) δ1.45 (t, 13.2 Hz, 12H), 2.13 (d, 12.6 Hz, 12H), 2.49 (t, 12.6 Hz, 12H), 2.69 (t, 12.6 Hz, 12H ), 3.29 (s, 18H), 3.52 (s, 18H), 4.48 (s, 12H), 4.51 (s, 12H), 6.92 (d, 8.4 Hz, 12H), 6.99 (s, 12H), 7.07 (d , 8.4 Hz, 12H), 7.86 (s, 6H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ31.9 (XH ₂ ), 34.2 (CH ₂ ), 55.3 (CH ₃ ), 56.6 (CH ₃ ), 77.9 (4 °), 78.5 (4 °), 91.6 (CH ₂ ), 92.7 (CH ₂ ), 125.7 (CH), 126.7 (CH), 127.3 (CH), 127.5 (CH), 138.3 (4 °), 139.0 (4 °), 139.1 (4 °), 144.3 (4 °); HRMS (FAB) m / z calcd for C ₁₂₆ H ₁₅₀ O ₂₄ Na [M + Na] ⁺ : 2071.0443, found 2071.0492; mp: 269.0 ° C .

Example 3-1: [6.6.6] Cage synthesis

[Wherein, MOM and DMSO are the same as above. ]
The box-shaped compound (5) obtained in Example 2-1 (13.0 mg, 5.71 μmol), NaHSO ₄ .H ₂ O (23.7 mg, 172 μmol), o-chloranil (20 μl) were placed in a 20 mL Schlenk tube with a magnetic stir bar. 6.96 mg, 28.3 μmol), dry m-xylene (2.5 mL), and dry dimethyl sulfoxide (DMSO) (0.5 mL) were added. The reaction mixture was stirred at 150 ° C. under air for 24 hours. After cooling to room temperature, the mixture was extracted with CHCl ₃ , washed with brine, dried over Na ₂ SO ₄ and concentrated under reduced pressure. The crude product was purified by PTLC (hexane / CH ₂ Cl ₂ = 1: 1), and the target compound [6.6.6] cage (1,8 (1,3,5) 2,3,4, 5,6,7,9,10,11,12,13,14,15,16,17,18,19,20 (1,4) -icosabenzenavicyclo [6.6.6] icosaphene; 1 , 8 (1, 3, 5) 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 (1, 4)- icosabenzenabicyclo [6. 6. 6] icosaphane) (1) was obtained as a white solid (6.0 mg, 69%).

¹ H NMR (600 MHz, CDCl ₃ ) δ 7.590 (d, J = 8.4 Hz, 12H), 7.593 (d, J = 8.6 Hz, 24H), 7.67 (d, J = 8.6 Hz, 12H), 7.69 (d , J = 8.6 Hz, 12H), 7.77 (d, J = 8.4 Hz, 12H), 7.85 (s, 6H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ124.6 (CH ₂ ), 127.08 (CH ₂ ), 127.13 (CH ₂ ), 127.4 (CH ₂ ), 127.5 (CH ₂ ), 127.7 (CH ₂ ), 127.8 (CH ₂ ), 138.3 (4 °), 138.4 (4 °), 138.8 (4 °), 139.0 (4 °), 139.3 (4 °), 139.6 (4 °), 141.5 (4 °); HRMS (MALDI-TOF) m / z calcd for C ₁₂₀ H ₇₈ [M] ⁺ : 1518.6104, found 1518.6111; mp : not decomposed nor melted over 300 ℃.

Example 3-2: [4.4.4] Cage synthesis

[Wherein, MOM and DMSO are the same as above. ]
In the same manner as in Example 3-1, the box compound (36) (10.5 mg, 5.77 μmol) obtained in Example 2-2 or Example 2-3 was used, and NaHSO ₄ .H ₂ O (26.9 mg, 195 μmol), o-chloranil (10.7 mg, 43.5 μmol), dry m-xylene (2.5 mL), and dry dimethyl sulfoxide (DMSO) (0.5 mL), reacted at 150 ° C. for 48 hours to be the target compound [4.4.4] The cage was obtained as a white solid (1.8 mg, 29%).
¹ H NMR (600 MHz, CDCl ₃ ) δ 7.468 (d, 8.4 Hz, 12H), 7.470 (d, 9.0 Hz, 12H), 7.52 (d, 9.0 Hz, 12H), 7.63 (d, 8.4 Hz, 12H) , 7.65 (s, 6H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ124.9 (CH), 127.25 (CH), 127.30 (CH), 127.7 (CH), 127.8 (CH), 138.1 (4 °) , 138.2 (4 °), 138.5 (4 °), 139.0 (4 °), 141.6 (4 °); HRMS (MALDI-TOF) m / z calcd for C ₈₄ H ₅₄ [M] ⁺ : 1062.4220, found; 1062.4251 .

Example 3-3: Synthesis of [5.5.5] cage

[Wherein, MOM and DMSO are the same as above. ]
In the same manner as in Example 3-1 and Example 3-2, the box-shaped compound (37) obtained in Example 2-4 (13.2 mg, 6.44 μmol) was used, and NaHSO ₄ .H ₂ O (27.6 mg, 200 μmol), o-chloranil (11.7 mg, 47.6 μmol), dry m-xylene (3.0 mL), and dry dimethyl sulfoxide (DMSO) (0.5 mL), reacted at 150 ° C. for 48 hours to be the target compound [5.5.5] Cage was obtained as a white solid (4.3 mg, 52%).
¹ H NMR (600 MHz, CDCl ₃ ) δ7.53 (d, 9.0 Hz, 12H), 7.54 (d, 8.4 Hz, 36H), 7.60 (s, 12H), 7.61 (d, 9.0 Hz, 12H), 7.79 (s, 6H); ¹³ C NMR (150 MHz, CDCl ₃ ) δ 124.6 (CH), 127.1 (CH), 127.3 (CH), 127.7 (CH), 127.8 (CH), 138.2 (4 °), 138.3 ( 4 °), 138.5 (4 °), 139.0 (4 °), 139.4 (4 °), 141.4 (4 °); HRMS (MALDI-TOF) m / z calcd for C ₁₀₂ H ₆₆ [M] ⁺ : 1290.5159, found; 1290.5200.

Experimental Example 1: Photophysical UV / VIS absorption spectra were recorded with a Shimadzu UV-3510 spectrometer with a resolution of 0.5 nm. The emission spectrum was measured using a Hitachi F-4500 spectrometer with a resolution of 0.2 nm. The solution was diluted with degassed spectral grade chloroform in a 1 cm square quartz cell. The absolute fluorescence quantum yield was measured with a Hamamatsu C9920-02 calibration integrating sphere system equipped with a multi-channel spectrometer (PMA-11). The fluorescence lifetime was measured with a picosecond fluorescence measurement system Hamamatsu C4780 equipped with a USHO pulse nitrogen laser (excitation wavelength of 10 Hz repetition rate was 337 nm).

[Two-photon absorption]
Two photon absorption (TPA) spectra were measured using the open aperture Z-scan method. A previously.SA femtosecond optical parametric amplifier (Spectra Physics OPA-800) was scanned over a wide range of excitation wavelengths (484 to 692 nm) as a light source at a repetition rate of 1 kHz. The output beam of the parametric amplifier was passed through a small iris and a nearly Gaussian spatial profile was obtained. The pulse width was measured by an autocorrelator (generally, the half width of a Gaussian pulse is 118 fs). The Rayleigh range Z _R of the optical setup was 7-14 mm depending on the wavelength used. The sample solution stayed in the quartz cuvette (path length L = 2 mm), ie shorter than Zr and satisfied the “optically thin state” L << Z _R (Sheik-Bahae, M .; Said, AA Wei, T.-H .; Hagan, DJ; Van Stryland, EW IEEE J. Quantum Electron. 1990, 26, 760.). Measurement, by the incident laser power P _i is changed in the range of 0.05 ~ 0.35 mW at each wavelength was repeated at least 4 times. Before each set of measurements, the solvent (spectral grade chloroform) was measured under the same conditions to check for the presence of unwanted nonlinear optical effects such as the stimulated Raman effect that appeared as a sharp dip in the Z-scan trace. The on-axis peak intensity I ₀ was less than 180 GW cm ^{−2 at the} focal point.

A typical recorded Z-scan trace is shown in FIGS. All recorded Z-scan traces are passed through a two-photon absorption medium (Kamada, K .; Matsunaga, K .; Yoshino, A .; Ohta, KJ Opt. Soc. Am. B 2003, 20, 529.) Analyzed with a theoretical model of Gaussian pulse transmittance and curve fitting procedure. From the curve fitting, the two-photon absorption q ₀ = α ⁽²⁾ I ₀ L of the sample was obtained (α ⁽²⁾ is the TPA coefficient). The observed signal resulting from the TPA process was confirmed, and the proportional relationship of q _{0 to} I ₀ , that is, _Pi was confirmed (FIGS. 3 and 4). The TPA cross section σ ⁽²⁾ was calculated based on the rule of σ ⁽²⁾ = E _ph α ⁽²⁾ / N (N is the number density of molecules in the sample calculated from the molar concentration, and E _ph is the incident laser Finally, σ ⁽²⁾ spectra were obtained by repeating measurements at different wavelengths.

The obtained σ ⁽²⁾ value is 1,4 of the previous report (Kennedy, SM; Lytle, FE Anal. Chem. 1986, 58, 2643.) as a standard substance measured under the same conditions (chloroform solution, 20 mM). Calibration was based on the value of bis (2-methylstyryl) benzene (bis-MSB). Since there was no report of a value at a wavelength shorter than 537 nm, a GaN single crystal (thickness 280 μm, semi-insulating) manufactured by Shinyo Co., Ltd. was measured together with a bis-MSB solution. First, the α ⁽²⁾ spectral shape of the previously reported GaN is expressed by the theoretical formula of the GaN TPA spectral shape (Sheik-Bahae, M .; Hutchings, DC; Hagan, DJ; Van Stryland, EW IEEE J. Quantum Electron. 1991, 27, 1296.), and σ ⁽²⁾ value of bis-MSB at wavelengths of 484 to 537 nm is shown at 540 to 600 nm in the previous report (Detailed procedure is in preparation to be presented elsewhere.) The calibration was performed based on the calibrated spectrum of GaN while keeping the average of the σ- ⁽²⁾ values of bis-MSB. Furthermore, at wavelengths longer than 600 nm, 1,4-bis (2,5-dimethoxy-4- {2- [4- (N-methyl) pyridine-1-iumyl] ethenyl} phenyl) butadiyne is used as a standard compound. Alignment of σ ⁽²⁾ values in Triflate (MPPBT) (Kamada, K .; Iwase, Y .; Sakai, K .; Kondo, K .; Ohta, KJ Phys. Chem. C 2009, 113, 11469.) Measured to check sex.

A sample solution (0.57 mm) of [6.6.6] carbon nanocage in spectroscopic grade chloroform was prepared in an air atmosphere. 2 ′ ″, 5 ′ ″-didecyl-1, 1 ′: 4 ′, 1 ″: 4 ″, 1 ′ ″: 4 ′ ″, 1 which is a linear oligoparaphenylene '': 4 '' '', 1 '' ': 4' '' '', 1 '' '' ''-septiphenyl (2 '' ', 5' ''-didecyl-p-septiphenyl) in chloroform (15 mM) was also prepared under atmospheric conditions. No signs of deterioration were observed in both samples after TPA measurement.

[Absorption and fluorescence]
[4.4.4] cage obtained in Example 3-2, [5.5.5] cage obtained in Example 3-3, [6.6.6] cage obtained in Example 3-1. The absorption and fluorescence spectra were measured. Cycloparaphenylene has the same absorption wavelength regardless of size (Patent Document 1; about 338 to 339 nm), whereas the absorption wavelength of the carbon nanocage shifted red as the cage size increased. Interestingly, however, maximum fluorescence shifted blue with increasing cage size. The energy difference between the maximum peaks corresponded to the oscillator strength of para-substituted benzene (about 1400-1500 cm ^-1 ). The [6.6.6] cage also showed strong blue fluorescence with a very high fluorescence quantum yield (Φ _F = 0.87). In the [6.6.6] cage, radioactive (kr) and non-radioactive (knr) determined from the fluorescence lifetime (τ _s = 1.4 ns) and the formula (Φ _F = kr × τ _s and kr + knr = τ _s ⁻¹ ) ) Was 6.2 × 10 ⁸ s ⁻¹ and 9.4 × 10 ⁷ s ⁻¹ , respectively. These values are comparable to cycloparaphenylene with 12 benzene rings ([12] CPP) (4.0 × 10 ⁸ s ⁻¹ and 5.0 × 10 ⁷ s ⁻¹ ). The results are shown in Table 5 and FIG. In FIG. 5, the solid lines are the absorption spectra of the [4.4.4] cage, the [5.5.5] cage, and the [6.6.6] cage in order from the left, and the broken line is from the left. In order are the fluorescence spectra of the [6.6.6] cage, the [5.5.5] cage, and the [4.4.4] cage.

Experimental Example 2: X-ray crystal structure analysis Using a CCD single crystal automatic X-ray structure analyzer “Saturn” (trade name) manufactured by Rigaku Corporation, obtained in Example 1-3 which is a precursor of the cage compound of the present invention X-ray structural analysis of the protected tribromobenzene tri-substituted product and the [4, 4, 4] cage obtained in Example 3-2 was performed. Single crystals were obtained by slowly adding diethyl ether (Et ₂ O) vapor to a THF solution at room temperature. As a result, it was shown that all of the protected tribromobenzene tri-substituted products obtained in Example 1-3 had a cis structure (FIG. 6). Moreover, the cage compound of the present invention had a beautiful cage structure (FIG. 7A). In addition, two THF molecules and one diethyl ether (Et ₂ O) molecule were incorporated into the cage (FIG. 8). Further, a slight shift of the benzene ring was shown in the appearance seen from above (FIG. 7B). The packing structure showed that the [4.4.4] cage was tightly packed (FIG. 7 (c)). The results are shown in Table 6 and FIGS.

Experimental example 3: Computer study The Gaussian 09 program run on the SGI Altix4700 system was used for optimization, TD-DFT (B3LYP / 6-31G (d)).

As a result, the [6.6.6] cage obtained in Example 3-1, the [5.5.5] cage obtained in Example 3-3, and the obtained in Example 3-2 [4.4. 4] The results of the cage are shown in FIG. In addition, FIG. 10 shows the frontier molecular orbitals of the [6.6.6] cage.

Claims

A box-shaped compound (B) in which eight or more rings are linked by a single bond,
The rings are bonded to each other with sp2 hybrid carbon atoms or sp3 hybrid carbon atoms present in the ring,
(1) Formula:

2 to 4 groups represented by
(2) consisting of 6 optionally substituted 1,4-cyclohexylene groups and (3) 0 or more divalent aromatic hydrocarbon groups optionally having substituents , Box-shaped compounds.
Formula (IIa):

[In the formula, three R 2 are the same or different and are each represented by the general formula (IIa-1):

(Wherein R 3 is the same or different, and each represents a hydrogen atom or a hydroxyl-protecting group; R 4 is the same or different, and each is a divalent aromatic hydrocarbon group optionally having a substituent; The same or different, each being an integer of 0 or more.)
It is a bivalent group shown by these. ]
The box-shaped compound of Claim 1 which is a compound shown by these.
A cage compound (A) in which eight or more rings are linked by a single bond,
The rings have sp2 hybrid carbon atoms present in the rings bonded to each other,
(1) Formula:

And (3) a method for producing a cage compound, comprising (3) 6 or more divalent aromatic hydrocarbon groups which may have a substituent,
A box-shaped compound (B) in which eight or more rings are linked by a single bond,
The rings are bonded to each other with sp2 hybrid carbon atoms or sp3 hybrid carbon atoms present in the ring,
(1) Formula:

2 to 4 groups represented by
(2) consisting of 6 optionally substituted 1,4-cyclohexylene groups and (3) 0 or more divalent aromatic hydrocarbon groups optionally having substituents The manufacturing method provided with the conversion process which converts the cyclohexane ring part which a box-shaped compound has into a benzene ring.
Before the conversion step,
General formula (III):

[Wherein R 3 is the same or different and each represents a hydrogen atom or hydroxyl-protecting group; R 4 is the same or different and each represents a divalent aromatic hydrocarbon group optionally having a substituent; The same or different, each an integer greater than or equal to 0; Y is the same or different and each represents a halogen atom or general formula (III-1):

(Wherein R 5 is the same or different and each represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R 5 is bonded to each other to form a ring with adjacent —O—B—O—. May be.)
It is group shown by these. ]
The manufacturing method of Claim 3 provided with the coupling process which couples compound (III) shown by these.
A cage compound in which eight or more rings are linked by a single bond,
The rings have sp2 hybrid carbon atoms present in the rings bonded to each other,
(1) Formula:

A cage compound comprising 2 to 4 groups represented by the formula (2) and (2) 6 or more divalent aromatic hydrocarbon groups which may have a substituent.
Formula (Ia):

[Wherein, R 1 is the same or different and each represents a general formula (Ia-1):

(In the formula, R 4 is the same or different and each is a divalent aromatic hydrocarbon group optionally having a substituent; n is the same or different and each is an integer of 0 or more.)
It is a bivalent group shown by these. ]
The cage compound according to claim 5, which is a compound represented by the formula:
The cage compound according to claim 6, wherein each R 4 is a group having a bond at the para position.
The cage compound according to any one of claims 5 to 7, wherein the total number of rings is 8 to 22.
A box-shaped compound (B) in which eight or more rings are linked by a single bond,
The rings are bonded to each other with sp2 hybrid carbon atoms or sp3 hybrid carbon atoms present in the ring,
(1) Formula:

2 to 4 groups represented by
(2) consisting of 6 optionally substituted 1,4-cyclohexylene groups and (3) 0 or more divalent aromatic hydrocarbon groups optionally having substituents A method for producing a box-shaped compound comprising:
General formula (III):

[Wherein R 3 is the same or different and each represents a hydrogen atom or hydroxyl-protecting group; R 4 is the same or different and each represents a divalent aromatic hydrocarbon group optionally having a substituent; The same or different, each an integer greater than or equal to 0; Y is the same or different and each represents a halogen atom or general formula (III-1):

(Wherein R 5 is the same or different and each represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R 5 is bonded to each other to form a ring with adjacent —O—B—O—. May be.)
It is group shown by these. ]
The manufacturing method provided with the coupling process which couples compound (III) shown by these.
General formula (III):

[Wherein R 3 is the same or different and each represents a hydrogen atom or hydroxyl-protecting group; R 4 is the same or different and each represents a divalent aromatic hydrocarbon group optionally having a substituent; The same or different, each an integer greater than or equal to 0; Y is the same or different and each represents a halogen atom or general formula (III-1):

(Wherein R 5 is the same or different and each represents a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and R 5 is bonded to each other to form a ring with adjacent —O—B—O—. May be.)
It is group shown by these. ]
A compound represented by