Halogenated cubane compound and production method for same

Abstract

The present invention provides: a novel compound in which some of the eight fluorine atoms of perfluorocubane are substituted with a halogen atom other than a fluorine atom; and a production method for the compound. The present invention relates to: the halogenated cubane compound represented by general formula (1) or (1') [in the formulas, X is an iodine atom, a bromine atom, or a chlorine atom]; and a production method for a halogenated cubane compound in which the halogenated cubane compound represented by general formula (1) or (1') is produced by using a basic catalyst and the halogenation agent represented by general formula (2) [in the formula, X is an iodine atom, a bromine atom, or a chlorine atom and Ar1 is an aryl group which may have a substituent or a heteroaryl group which may have a substituent] to halogenate hexafluorocubane or heptafluorocubane.

Description

Halogenated cubane compounds and methods for producing the same

[0001] The present invention relates to a halogenated cubane compound in which one or two of the eight fluorine atoms of perfluorocubane (octafluorocubane) are substituted with a halogen atom other than a fluorine atom, and a method for producing the same. This application claims priority to Japanese Patent Application No. 2023-177884 filed in Japan on October 13, 2023, and Japanese Patent Application No. 2024-009991 filed in Japan on January 26, 2024, the contents of which are incorporated herein by reference.

[0002] Polyhedral cage-forming hydrocarbons such as fullerenes, dodecahedranes, and cubanes can encapsulate guest molecules in their internal cavities. In particular, perfluorinated compounds of these polyhedral hydrocarbons can encapsulate electrons within the cage. This encapsulation is theoretically thought to arise from the stable vacant orbitals within the cage, which are derived from the multiple σ* orbitals of the C-F bond.

[0003] Perfluorocubane, whose structure was proposed in 2004 (Non-Patent Document 1), was theoretically predicted to have less steric hindrance than other perfluoropolyhedral hydrocarbons and to be able to stably accept electrons into the cage (Non-Patent Document 2). Subsequently, in 2022, perfluorocubane was synthesized by the PERFECT method, which involves the direct fluorination of a partially fluorinated ester using excess fluorine gas in a fluorinated solvent, and further analysis was carried out (Non-Patent Document 3). Examination of the radical anion of perfluorocubane using matrix isolation electron spin resonance spectroscopy revealed that the unpaired electron accepted by perfluorocubane is mainly located within the cage.

[0004] Kato, et al., Journal of Chemical Physics, 2004, vol.120(2), p.1006-1016.Irikura, The Journal of Physical Chemistry A, 2008, vol.112, p.983-988.Sugiyama, et al., Science, 2022, vol.377, p.756-759.

[0005] Perfluorocubane, which accepts electrons inside the cage, is completely different from typical π-conjugated electron acceptors that capture electrons on the molecular surface. This makes it promising for a variety of applications, including the development of new conductive materials. However, perfluorocubane is very stable, making it difficult to use as a substrate for synthetic reactions.

[0006] An object of the present invention is to provide a novel compound in which some of the eight fluorine atoms of perfluorocubane have been substituted with halogen atoms other than fluorine atoms, and a method for producing said compound.

[0007] The present inventors have discovered that halogenated cubane compounds in which two or one of the eight fluorine atoms of perfluorocubane have been substituted with halogen atoms other than fluorine atoms can be obtained by halogenating hexafluorocubane or heptafluorocubane with a specific halogenating agent and a base catalyst, and have completed the present invention.

[0008] That is, the present invention is as follows: [1] A compound represented by the following general formula (1) or (1′):

[0009]

[0010] [wherein X is an iodine atom, a bromine atom, or a chlorine atom]. [2] A halogenated cubane compound according to the above [1], wherein X is an iodine atom. [3] A halogenated cubane compound according to the above [1] or [2], wherein the two Xs in the general formula (1) are the same type of atom. [4] A halogenated cubane compound according to the above [1] or [2], wherein hexafluorocubane or heptafluorocubane is reacted with a compound represented by the following general formula (2):

[0011]

[0012] wherein X is an iodine atom, a bromine atom, or a chlorine atom; １ is an unsubstituted aryl group, a substituted aryl group, an unsubstituted heteroaryl group, or a substituted heteroaryl group], and a base catalyst to obtain a compound represented by the following general formula (1) or (1′):

[0013]

[0014] [wherein X is an iodine atom, a bromine atom, or a chlorine atom]. [5] A method for producing a halogenated cubane compound according to the above [4], wherein the base catalyst is LiHMDS, P4-tBu, or KOtBu / 18-crown-6. [6] A method for producing a halogenated cubane compound according to the above [4] or [5], wherein the halogenation of hexafluorocubane or heptafluorocubane with the halogenating agent is carried out at -100 to 70°C. [7] A method for producing a halogenated cubane compound according to any of the above [4] to [6], wherein the halogenation of hexafluorocubane or heptafluorocubane with the halogenating agent is carried out in an ether-based solvent. [8] A method for producing a halogenated cubane compound according to any of the above [4] to [7], wherein the aryl group is a phenyl group, a naphthyl group, an anthryl group, or a 9-fluorenyl group. [9] The method for producing a halogenated cubane compound according to any one of [4] to [8], wherein the heteroaryl group is a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazolyl group, a quinolyl group, an isoquinolyl group, a pyrrolyl group, an imidazolyl group, an indolyl group, a furyl group, a benzofuryl group, a thienyl group, a benzothienyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, or an isothiazolyl group.

[10] The method for producing a halogenated cubane compound according to any one of [4] to [9], wherein the substituent is one or more selected from the group consisting of a halogen atom, an alkyl group, an alkenyl group, an alkoxy group, an aryl group, an acyl group, a hydroxy group, a carboxy group, an alkyloxycarbonyl group, an aryloxycarbonyl group, a cyano group, an amino group, and a nitro group.

[11] The method for producing a halogenated cubane compound according to any one of [4] to

[10] , wherein X is an iodine atom.

[0015] According to the present invention, it is possible to obtain a novel halogenated cubane compound in which one or two of the eight fluorine atoms of perfluorocubane have been substituted with halogen atoms other than fluorine atoms.

[0016] In the present invention and the present specification, "C ｐ１－ｐ２ " (p1 and p2 are positive integers satisfying p1<p2) means that the group has p1 to p2 carbon atoms.

[0017] In the present invention and the present specification, "C １－６ The "alkyl group" is an alkyl group having 1 to 6 carbon atoms, and may be a straight chain or a branched chain. １－６ Examples of the alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, and a hexyl group.

[0018] In the present invention and the present specification, "C １－６ The "alkoxy group" is a C １－６ A group in which an oxygen atom is bonded to the bonding terminal of an alkyl group. １－６ The alkoxy group may be a straight chain or a branched chain. １－６ Examples of the alkoxy group include a methoxy group, an ethoxy group, a propoxy group, a butoxy group, a tert-butoxy group, a pentyloxy group, and a hexyloxy group.

[0019] In the present invention and the present specification, "C ２－６ The term "alkenyl group" refers to an alkyl group having 2 to 6 carbon atoms in which at least one carbon-carbon bond is unsaturated. ２－６ The alkenyl group may be a straight chain or a branched chain. ２－６ Examples of the alkenyl group include a vinyl group, an allyl group, a butenyl group, a pentenyl group, and a hexenyl group.

[0020] In the present invention and the present specification, "C ２－７ An "acyl group" is an acyl group in which the hydrocarbon group moiety obtained by removing the carbonyl group is C １－６ Alkyl group, C ２－６ The term "acyl group" refers to a group that is an alkenyl group, a 5- or 6-membered aryl group, or a 5- or 6-membered heteroaryl group. The hydrocarbon group portion of the acyl group may be linear or branched. ２－７Examples of the acyl group include a formyl group, an acetyl group, a propanoyl group, a propenoyl group, and a benzoyl group.

[0021] In the following description, "compound (n)" means a compound represented by formula (n).

[0022] <Halogenated cubane compound> The halogenated cubane compound according to the present invention is a compound represented by the following general formula (1) or (1'). In general formulas (1) and (1'), X represents an iodine atom, a bromine atom, or a chlorine atom. The two Xs in general formula (1) represent the same type of atom.

[0023]

[0024] Perfluorocubane is very stable and has poor reactivity, whereas the halogenated cubane compounds of the present invention, in which one or two of the eight fluorine atoms are substituted with halogen atoms other than fluorine atoms, are more reactive than perfluorocubane. In particular, the halogenated cubane compound of the present invention is preferably a compound in which X is an iodine atom (1,2,3,4,6,7-hexafluoro-5,8-diiodocubane).

[0025] The halogenated cubane compounds according to the present invention, like perfluorocubane, can stably accept electrons into the cage. That is, the halogenated cubane compounds according to the present invention are electron acceptors that contain electrons and have the reactivity to react with other substances. Therefore, the halogenated cubane compounds according to the present invention are useful as raw materials for functional organic materials.

[0026] <Method for Producing Halogenated Cubane Compound> The method for producing a halogenated cubane compound according to the present invention (hereinafter sometimes referred to as the "production method according to the present invention") is a method for producing a halogenated cubane compound according to the present invention. Specifically, the halogenated cubane compound represented by general formula (1) or (1') is produced by halogenating hexafluorocubane (1,2,3,4,6,7-hexafluorocubane) or heptafluorocubane (1,2,3,4,5,6,7-heptafluorocubane) using a specific halogenating agent and a base catalyst.

[0027] The starting compound, 1,2,3,4,6,7-hexafluorocubane, can be synthesized from 1,4-cubanedicarboxylic acid (CAS number 32846-66-5) by the synthesis method described in Non-Patent Document 3. 1,2,3,4,5,6,7-heptafluorocubane can be synthesized from cubane-1-carboxylic acid (CAS number 53578-15-7) by the synthesis method described in Non-Patent Document 3.

[0028] In the production method according to the present invention, the halogenating agent used for halogenating hexafluorocubane or heptafluorocubane is a halogenating agent represented by the following general formula (2).

[0029]

[0030] In general formula (2), X is an iodine atom, a bromine atom, or a chlorine atom. The halogenating agent represented by general formula (2) used in the production method of the present invention is appropriately determined depending on the halogenated cubane compound to be produced. When producing a halogenated cubane compound in which two Xs in general formula (1) are iodine atoms, a halogenating agent in which X in general formula (2) is an iodine atom is used. When producing a halogenated cubane compound in which one X in general formula (1') is an iodine atom, a halogenating agent in which X in general formula (2) is an iodine atom is used.

[0031] In general formula (2), Ar １is an unsubstituted aryl group, a substituted aryl group, an unsubstituted heteroaryl group, or a substituted heteroaryl group. The aryl group is not particularly limited, and examples thereof include a phenyl group, a naphthyl group, an anthryl group, and a 9-fluorenyl group, with a phenyl group being particularly preferred. The heteroaryl group is not particularly limited, and examples thereof include a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazolyl group, a quinolyl group, an isoquinolyl group, a pyrrolyl group, an imidazolyl group, an indolyl group, a furyl group, a benzofuryl group, a thienyl group, a benzothienyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, and an isothiazolyl group.

[0032] A "substituted aryl group" is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to a carbon atom of an aryl group have been substituted with other functional groups. Similarly, a "substituted heteroaryl group" is a group in which one or more, preferably 1 to 3, hydrogen atoms bonded to a carbon atom of a heteroaryl group have been substituted with other functional groups. When a heteroaryl group has two or more substituents, the substituents may be the same or different.

[0033] Ar １ Examples of the substituents of the aryl group and heteroaryl group include a halogen atom, an alkyl group, an alkenyl group, an alkoxy group, an aryl group, an acyl group, a hydroxy group, a carboxy group, an alkyloxycarbonyl group, an aryloxycarbonyl group, a cyano group, an amino group, and a nitro group. １－６ The alkyl group is preferred, and the alkenyl group is C ２－６ The alkyl group is preferred, and the alkoxy group is C １－６ Alkoxy groups are preferred, and C ２－７ An acyl group is preferred. As the alkyloxycarbonyl group, the alkyl group portion is C １－６ A group which is an alkyl group is preferred, and the alkyl group portion is C １－３A group that is an alkyl group is more preferred. As the aryloxycarbonyl group, a group in which the aryl group moiety is a phenyl group is preferred.

[0034] The halogenation of hexafluorocubane or heptafluorocubane with a halogenating agent represented by the general formula (2) can be carried out by the reaction of CF ３ The reaction proceeds under conditions known to cause deprotonation of -H. For this reason, the base catalyst used in the reaction of hexafluorocubane or heptafluorocubane with the halogenating agent represented by general formula (2) is preferably a strong base catalyst, and LiHMDS (lithium hexamethyldisilazane), P4-tBu (phosphazene base), or KOtBu (potassium tert-butoxide) / 18-crown-6 (1,4,7,10,13,16-hexaoxacyclooctadecane) is preferred, with LiHMDS being particularly preferred.

[0035] The reaction temperature during the halogenation reaction is not particularly limited as long as it is a temperature at which the reaction can proceed, and can be appropriately determined taking into consideration the type of halogenating agent used, etc. The reaction temperature for the halogenation reaction in the production method according to the present invention can be set within the range of -100 to 70°C, and preferably within the range of -80 to 40°C. When LiHMDS is used as the halogenating agent, the reaction temperature is particularly preferably within the range of -80 to -40°C.

[0036] The solvent used in the halogenation reaction may be any solvent that can dissolve the raw material compounds and is inert to the reaction, and may be appropriately selected from known solvents used in chemical reactions. From the viewpoint of the solubility of hexafluorocubane or heptafluorocubane, the solvent is preferably an ether-based solvent, more preferably tetrahydrofuran (THF), diethyl ether, 1,4-dioxane, 1,2-dimethoxyethane, or cyclopentyl methyl ether, and particularly preferably tetrahydrofuran. The solvent used in the halogenation reaction may consist of only one type of solvent, or may be a mixed solvent of two or more types of solvents.

[0037] The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[0038] The NMR apparatus used in the analyses of the Examples and Comparative Examples was a JNM-ECZ400S (400 MHz) manufactured by JEOL Ltd. １ H NMR showed tetramethylsilane at 0 ppm, １９ F NMR shows C ６ F ６ was set as the reference value of -162 ppm.

[0039] Example 1 1,2,3,4,6,7-hexafluoro-5,8-diiodocubane was synthesized.

[0040]

[0041] To a glass vessel equipped with a stir bar, hexafluorocubane (49.7 mg, 234 μmol) and THF (anhydrous, 10 mL) were added under a nitrogen atmosphere. Lithium hexamethyldisilazide (1.3 M in THF, 0.91 mL, 5.1 equiv.) was then added dropwise at −78° C., followed by the addition of p-toluenesulfonyl iodide (343.1 mg, 1.22 mmol, 5.2 equiv.) in THF (2.0 mL) at −78° C. The resulting reaction mixture was stirred under a nitrogen atmosphere at −78° C. for 10 minutes. １９ The reaction mixture was monitored using F NMR. To ensure complete conversion of the hexafluorocubane, lithium hexamethyldisilazide (1.3 M in THF, 0.18 mL, 1.0 equiv.) was added. After warming the reaction mixture to room temperature, the pale yellow suspension was passed through alumina using THF as the eluent. The solvent was then removed using atmospheric distillation (100°C). 1,2,3,4,6,7-hexafluoro-5,8-diiodocubane (50.9 mg, 47% yield) was obtained as a colorless solid by sublimation from the oily residue (160°C, 5 torr).

[0042] 13 C{ 19 F} NMR (101 MHz, acetone-d6) δ 101.55, 33.26. 19 F NMR (376 MHz, acetone-d6) δ -173.09 (s, 6F).

[0043] Example 2 1,4-Dibromo-2,3,5,6,7,8-hexafluorocubane was synthesized.

[0044]

[0045] To a glass vessel equipped with a stir bar, hexafluorocubane (47.1 mg, 222 μmol) and 4-methoxybenzenesulfonyl bromide (175.8 mg, 700 μmol, 3.2 equiv.) were added THF (anhydrous, 5 mL) under a nitrogen atmosphere. Lithium hexamethyldisilazide (1.3 M in THF, 0.90 mL, 5.3 equiv.) was then added dropwise at −78° C., and the resulting reaction mixture was stirred at −78° C. for 20 minutes under a nitrogen atmosphere. After the reaction mixture was warmed to room temperature, NH ４ The mixture was quenched with Cl and the dark brown suspension was passed through alumina using THF as eluent. The solvent was then removed using atmospheric distillation (110°C). 1,4-Dibromo-2,3,5,6,7,8-hexafluorocubane (16.1 mg, 20% yield) was obtained as a colorless solid by sublimation (160°C, 5 torr) from the oily residue.

[0046] 13 C{ 19 F} NMR (101 MHz, acetone-d6) δ102.60, 60.42. 19 F NMR (376 MHz, acetone-d6) δ -182.50 (s, 6F).

[0047] Example 3 1,4-dichloro-2,3,5,6,7,8-hexafluorocubane was synthesized.

[0048]

[0049] To a glass vessel equipped with a stir bar, hexafluorocubane (47.8 mg, 225 μmol) and 4-methoxybenzenesulfonyl chloride (106.8 mg, 516 μmol, 2.3 equiv.) were added THF (anhydrous, 10 mL) under a nitrogen atmosphere. Lithium hexamethyldisilazide (1.3 M in THF, 1.00 mL, 5.8 equiv.) was then added dropwise at −78° C., and the resulting reaction mixture was stirred at −78° C. for 20 minutes under a nitrogen atmosphere. After the reaction mixture was warmed to room temperature, NH ４ The mixture was quenched with Cl and the dark brown suspension was passed through alumina using THF as eluent. The solvent was then removed using atmospheric distillation (110°C). 1,4-Dichloro-2,3,5,6,7,8-hexafluorocubane (15.8 mg, 25% yield) was obtained as a colorless solid by sublimation (140°C, 5 torr) from the oily residue.

[0050] 13 C{ 19 F} NMR (101 MHz, acetone-d6) δ 103.43, 72.40. 19 F NMR (376 MHz, acetone-d6) δ -187.98 (s, 6F).

[0051] Example 4 1,2,3,4,5,6,7-heptafluoro-8-iodocubane was synthesized.

[0052]

[0053] To a glass vessel equipped with a stir bar, heptafluorocubane (2.3 mg, 10 μmol) and THF (anhydrous, 0.5 mL) were added under a nitrogen atmosphere. Lithium hexamethyldisilazide (1.3 M in THF, 0.04 mL, 5 equiv.) was then added dropwise at −78°C, followed by the addition of a solution of p-toluenesulfonyl iodide (14.0 mg, 0.050 mmol, 5 equiv.) in THF (0.5 mL) at −78°C. The resulting reaction mixture was stirred at −78°C for 10 minutes under a nitrogen atmosphere. After warming the reaction mixture to room temperature, the resulting pale yellow suspension was passed through alumina using THF as the eluent. The solvent was then removed using atmospheric distillation (100°C). Sublimation (160° C., 5 torr) from the oily residue afforded 1,2,3,4,5,6,7-heptafluoro-8-iodocubane (2.3 mg, 65% yield) as a colorless solid.

[0054] 19 F NMR (376 MHz, acetone-d6) -183.76--184.14 (m, 3F), -187.48--187.77 (m, 3F), δ -207.93--208.39 (m, 1F).

Claims

1. A compound represented by the following general formula (1) or (1'): A halogenated cubane compound represented by the formula: wherein X is an iodine atom, a bromine atom, or a chlorine atom.

2. The halogenated cubane compound according to claim 1, wherein X is an iodine atom.

3. The halogenated cubane compound according to claim 1 or 2, wherein the two Xs in the general formula (1) are the same type of atoms.

4. Hexafluorocubane or heptafluorocubane is reacted with a compound represented by the following general formula (2): [Wherein, X is an iodine atom, a bromine atom, or a chlorine atom; Ar １ is an unsubstituted aryl group, a substituted aryl group, an unsubstituted heteroaryl group, or a substituted heteroaryl group] and a base catalyst to obtain a halogenating agent represented by the following general formula (1) or (1′): A method for producing a halogenated cubane compound, comprising producing a halogenated cubane compound represented by the following formula: wherein X is an iodine atom, a bromine atom, or a chlorine atom.

5. The method for producing a halogenated cubane compound according to claim 4, wherein the base catalyst is LiHMDS, P4-tBu, or KOtBu / 18-crown-6.

6. The method for producing a halogenated cubane compound according to claim 4, wherein the halogenation of hexafluorocubane or heptafluorocubane with the halogenating agent is carried out at -100 to 70°C.

7. The method for producing a halogenated cubane compound according to claim 4, wherein the halogenation of hexafluorocubane or heptafluorocubane with the halogenating agent is carried out in an ether solvent.

8. The method for producing a halogenated cubane compound according to claim 4, wherein the aryl group is a phenyl group, a naphthyl group, an anthryl group, or a 9-fluorenyl group.

9. A method for producing a halogenated cubane compound as described in claim 4, wherein the heteroaryl group is a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazolyl group, a quinolyl group, an isoquinolyl group, a pyrrolyl group, an imidazolyl group, an indolyl group, a furyl group, a benzofuryl group, a thienyl group, a benzothienyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, or an isothiazolyl group.

10. The method for producing a halogenated cubane compound according to claim 4, wherein the substituent is one or more selected from the group consisting of a halogen atom, an alkyl group, an alkenyl group, an alkoxy group, an aryl group, an acyl group, a hydroxy group, a carboxy group, an alkyloxycarbonyl group, an aryloxycarbonyl group, a cyano group, an amino group, and a nitro group.

11. The method for producing a halogenated cubane compound according to claim 4, wherein X is an iodine atom.