JP2007055946A - Azacalixarene and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an azacalixarene which is a new cyclic compound cross-linked with reactive secondary amino groups. <P>SOLUTION: The azacalixarene is the new cyclic compound which is a cyclic compound composed of 2, 3 and 4 repeating constituent units and represented by formula (1) (wherein, R represents a 1-8C alkyl group; and m represents an integer of 2, 3 or 4). The new cyclic compound is cross-linked with the reactive secondary amino groups. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an azacalixarene, which is a cyclic compound having a cyclic amino group having a secondary amino group as a bridging group, a production method thereof, and a preferred use thereof.

  It is known that cyclic compounds having an aromatic ring in the structure are generally stable and have almost no strain, so that specific molecules can be recognized and included depending on the size of the inner pores of the ring structure. (For example, Kiichi Takemoto, Miki Miyata, Keiichi Kimura, “Clusion Compounds”, Tokyo Chemical Dojin, page 25 (1989); Non-Patent Document 1).

  In addition, it is known that various aromatic amines can be efficiently obtained by the reaction of a halogenated aromatic compound and an amine using a palladium complex catalyst (for example, Journal of Synthetic Organic Chemistry, Vol. 59, page 607 ( 2001); Non-Patent Document 2), a method for producing these aromatic amines has been proposed, for example, in JP-A-97451. It has been proposed to produce polymers and cyclic compounds by applying such production methods to difunctional dihalogenated aromatic compounds and diamino compounds (for example, Handbook of Organopalladium Chemistry for Organic Synthesis, 1 Volume, John Wiley & Sons Inc., page 1051 (2002);

  In the study of cyclic inclusion compounds, it is desired to develop a material having physical properties not found in conventional cyclic host molecules by introducing various substituents into the cyclic compound. For example, a cyclic compound in which a hydroxyl group of an aromatic ring unit of calixarene (this “calix” means “holy grail”) is converted by a substitution reaction and a tertiary phosphino group is introduced has a coordination ability to a transition metal. It has been reported that a cyclic host molecule that is expressed and has both molecular recognition ability and catalytic function can be provided (for example, Coord. Chem. Rev. 165, 93 (1997); Non-Patent Document 4).

  Since azacalixarene is a cyclic compound having an amino group as a crosslinking group, it is expected that various physical properties can be introduced into the crosslinking group to develop new physical properties.

  However, in the production of azacalixarene, when the above-described conventional method is used, the diamino compound that is the starting material is limited to the secondary diamino compound, so the amino group that is the crosslinking group of the resulting cyclic compound On the other hand, it is necessary to introduce a substituent in the production stage in advance. Therefore, in order to convert the substituent of the bridging group of the cyclic compound, a starting material having a substituent introduced in advance is synthesized in the production stage, and moreover, each of these “starting materials having a substituent introduced beforehand” is suitable. About the manufacturing method of a cyclic compound, it is necessary to repeat trial & error, such as prior examination and experiment, for each starting material many times. Such a manufacturing method suitable for different starting materials is not only complicated by repeating trials and errors many times, but also the manufacturing conditions need to be separately examined and optimized, which further complicates.

  When a reactive secondary amino group is introduced into the crosslinking group of the cyclic compound, it can be used as a cyclic compound that can be arbitrarily converted into various derivatives by substitution and addition reactions, and can be adapted to various purposes. It is expected that a cyclic inclusion compound can be provided. However, when a condensation reaction is carried out using a primary diamino compound as a starting material by a conventional method, the formation of a chain compound, that is, an acyclic polymer is prioritized, and a cyclic group having a secondary amino group as a crosslinking group. Azacalixarene, which is a compound, is not produced, or only a trace amount of product can be confirmed by separation and extraction. Therefore, the synthesis of azacalixarene, which is a cyclic compound having a secondary amino group as a bridging group, is very inefficient (UK Patent No. 989560 (Patent Document 1); and Nature, No. 4883, 1963). June 1 (Non-Patent Document 5)).

British Patent No. 989560 Kiichi Takemoto, Miki Miyata, Keiichi Kimura, “The Inclusion Compound”, Tokyo Chemical Doujin, 25 (1989) Journal of Synthetic Organic Chemistry, Japan, 59, 607 (2001) Handbook of Organopalladium Chemistry for Organic Synthesis, 1 volume, John Wiley & Sons Inc., page 1051 (2002) Coord. Chem. Rev. 165, 93 (1997) Nature, No. 4883, June 1, 1963

  An object of the present invention is to provide an azacalixarene compound and a derivative thereof that can eliminate the above-mentioned drawbacks of the prior art.

  Another object of the present invention is to provide an azacalixarene compound and a derivative thereof capable of introducing various substituents into a bridging group to express new physical properties.

  As a result of diligent research, the present inventor has solved the above problem by constructing a molecule such that the “NH” group constituting the azacalix ring faces the “outside” of the azacalix ring using hydrogen bonding. Has been found to be extremely effective.

  The azacalixarene of the present invention is based on the above findings. More specifically, the following formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4).

  According to the present invention, 1,3-dihalogenated benzene and 4,6-dialkoxy-1,3-phenylenediamine (the alkoxy group is an alkoxy group having 1 to 8 carbon atoms), or

  1,3-dihalogenated-4,6-dialkoxybenzene and 1,3-phenylenediamine (the alkoxy group is an alkoxy group having 1 to 8 carbon atoms) are subjected to a condensation reaction in the presence of a palladium complex catalyst. Formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4)
A method for producing an azacalixarene represented by the formula is provided.

  According to the present invention, the following formula (2):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3, or 4).

  According to the present invention, the following formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4), a substitution reaction or addition in a secondary amino group which is a bridging group of azacalixarene By introducing a substituent into the cross-linking group by carrying out the reaction, the following formula (2):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3 or 4, and a method for producing an azacalixarene derivative is provided.

  According to the present invention, an inclusion complex further comprising a guest molecule and a host molecule corresponding to the guest molecule; and the host molecule is represented by the following formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4), or the following formula (2):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3 or 4), and an inclusion complex is provided.

  In the prior art, the raw material compound in which the N atom is modified is directly made into a ring. Therefore, as long as the raw material compound in which the N atom is modified is used “as is”, the structure of the obtained cyclic compound is naturally strongly influenced by the structure of the raw material compound itself.

  On the other hand, the azacalixarene of the present invention having the above-described configuration has an advantage that the degree of freedom of subsequent modification is extremely large because the “NH” group remains in the azacalix ring.

  In the prior art, when the raw material compound has an NH group, it is difficult to form a ring and the polymerization reaction tends to be dominant. According to the knowledge of the present inventor, the reason why the polymerization reaction is dominant in this way is that the zigzag shape (line) is suitable for the polymerization reaction rather than being cyclic (generally disadvantageous in terms of energy). It is presumed that the structure is more energetically advantageous.

  In the azacalixarene of the present invention, it is important that an OR group is added so that the “NH” group faces the “outside” of the azacalix ring (according to the inventor's knowledge, this If the “NH” group faces “inside” the azacalix ring, it tends to polymerize).

  As described above, in the present invention, the cyclization reaction is promoted by intramolecular hydrogen bonding, and an azacalixarene, which is a novel cyclic compound crosslinked with a reactive secondary amino group, is obtained. There is. The azacalixarene of the present invention provides various cyclic compound derivatives by, for example, further performing a substitution reaction or addition reaction on the secondary amino group of the crosslinking group of the cyclic compound. It can also be used as a core molecule for providing cyclic inclusion compounds having different inclusion functions.

  In a preferred embodiment of the present invention, 4,6-dialkoxy-1,3-phenylenediamine and 1,3-dihalogenated benzene or 1 having an alkoxy group having a hydrogen bonding interaction with a secondary amino group , 3-Dihalogenated-4,6-dialkoxybenzene and 1,3-phenylenediamine (wherein the alkoxy group represents an alkoxy group having 1 to 8 carbon atoms) as starting materials, and a carbon-nitrogen bond formation reaction The azacalixarene compound represented by the formula (1), which is a cyclic compound having a reactive secondary amino group (formula, m is an integer of 2, 3 or 4) Can be manufactured.

  According to another preferred embodiment of the present invention, a secondary amino group which is a bridging group of an azacalixarene compound represented by the formula (1) (wherein m is an integer of 2, 3 or 4) By carrying out a substitution reaction or an addition reaction in, a substituent can be introduced into the bridging group to produce a compound of formula (2) (wherein m is an integer of 2, 3 or 4).

  According to the present invention, for example, an alkoxy group having a hydrogen bonding interaction with a secondary amino group is introduced, and an intermediate of the cyclic compound generation process is performed by an intramolecular hydrogen bonding interaction between the secondary amino group and the alkoxy group. By controlling the three-dimensional structure of the body, it is possible to produce and isolate a cyclic compound crosslinked with a secondary amino group.

  Furthermore, since it is possible to introduce a substituent into the crosslinking group by performing a substitution reaction or addition reaction at the secondary amino group that is a crosslinking group, it can be used as a core molecule that can be arbitrarily converted into various derivatives. It is also possible to provide a cyclic host molecule that can be adapted to various purposes.

  The azacalixarene, which is a cyclic compound of the present invention, is generally soluble in an organic solvent and has a reactive secondary amino group, so that various cyclic compounds can be provided by various substitution reactions and addition reactions. .

  In addition, since the production method of the present invention can provide three types of cyclic compounds having different repeating structural units, that is, different ring sizes, a cyclic inclusion complex corresponding to the size of an ion or molecule serving as a guest of the inclusion complex is obtained. Can be provided.

  As described above, according to the present invention, there is provided an azacalixarene in which the “NH” group constituting the azacalix ring remains and the “NH” group faces the “outside” of the azacalix ring.

  Hereinafter, the present invention will be described more specifically. In the following description, “parts” and “%” representing the quantity ratio are based on mass unless otherwise specified.

(Azacalix Arene)
The azacalixarene of the present invention is a cyclic compound having the following formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4). R is preferably an alkyl group having 1 to 6 carbon atoms (more preferably an alkyl group having 1 to 4 carbon atoms) from the viewpoint of intramolecular hydrogen bonding interaction with a secondary amino group and steric hindrance.

  In the azacalixarene of the present invention, the “NH” group constituting the azacalix ring remains, and the “NH” group faces the “outside” of the azacalix ring. Furthermore, in the azacalixarene of the present invention, the fact that the “NH” group faces the “outside” of the azacalix ring is based on hydrogen bonding.

(Confirmation that NH group remains)
In the azacalixarene of the present invention, “the NH group remains” can be suitably confirmed, for example, by the following method.

^The signal attributed to the secondary amino group can be confirmed by ¹ H NMR (nuclear magnetic resonance) spectroscopy.
An absorption peak based on the secondary amino group can be confirmed by IR (infrared) spectroscopy.

(Confirmation that the NH group faces the outside of the ring)
In the azacalixarene of the present invention, it can be suitably confirmed, for example, by the following method, that the “NH group faces the outside of the ring”.

  X-ray crystal structure analysis confirms that the NH group faces outward.

(Confirmation that the NH group faces the outside of the ring due to the effect of hydrogen bonding)
In the azacalixarene of the present invention, it can be suitably confirmed, for example, by the following method, that “the NH group faces the outside of the ring due to the influence of hydrogen bonding”.

  X-ray crystal structure analysis confirms that the NH group faces the outside of the ring due to the influence of hydrogen bonding.

(Method for producing Azacalixarene)
In the present invention, the method for producing the azacalixarene compound represented by the above formula (1) is not particularly limited. From the viewpoint of synthesizing the azacalixarene compound represented by the above formula (1) (m is an integer of 2, 3 or 4) in one step, the following method is preferably used.

(One aspect of preferred method for producing azacalixarene)
The azacalixarene compound represented by the above formula (1) (m is an integer of 2, 3 or 4) is composed of 1,3-dihalogenated benzene and 4,6-dialkoxy-1,3-phenylenediamine ( An alkoxy group represents an alkoxy group having 1 to 8 carbon atoms), or 1,3-dihalogenated-4,6-dialkoxybenzene and 1,3-phenylenediamine (an alkoxy group represents an alkoxy group having 1 to 8 carbon atoms). ) In the presence of a palladium complex catalyst,

(Wherein R represents an alkyl group having 1 to 8 carbon atoms)
It can manufacture by the condensation reaction represented by these.

  R is preferably an alkyl group having 1 to 6 carbon atoms (more preferably an alkyl group having 1 to 4 carbon atoms) from the viewpoint of intramolecular hydrogen bonding interaction with a secondary amino group and steric hindrance. From the viewpoint of intramolecular hydrogen bonding interaction with the secondary amino group and steric hindrance, the alkoxy group is an alkoxy group having 1 to 6 carbon atoms (and further an alkoxy group having 1 to 4 carbon atoms). preferable.

  In the above reaction, a palladium complex catalyst synthesized in the reaction system immediately before the reaction may be used as it is, or a previously synthesized and isolated catalyst may be used. Such a palladium complex catalyst is preferably a palladium complex produced by a method of a reduction reaction and a ligand exchange reaction in the presence of a neutral ligand. Examples of neutral ligands in this case include 9,9-dimethyl-4,5-bis (difernylphosphino) xanthene and bis (diphenylphosphino) binaphthyl (used in this case). For details of possible palladium complex catalysts and neutral ligands, for example, Non-Patent Documents 2 and 3 described above can be referred to as necessary).

(Another embodiment of a preferred method for producing azacalixarene)
Azacalixarene, which is a cyclic compound having a secondary amino group as a bridging group, consisting of 2,3,4 repeating units, that is, an azacalixarene compound represented by the following formula (1) (m is 2, 3 or 4) is 1,3-dihalogenated benzene and 4,6-dialkoxy-1,3-phenylenediamine (the alkoxy group represents an alkoxy group having 1 to 8 carbon atoms) or 1,3-dihalogen -4,6-dialkoxybenzene and 1,3-phenylenediamine (the alkoxy group represents an alkoxy group having 1 to 8 carbon atoms) can be produced by a condensation reaction in the presence of a palladium complex catalyst.

  The palladium complex catalyst that can be used in this case is basically the same as that used when the compound of the above formula (1) is produced.

(Azacalixarene derivative (2))
According to the present invention, an azacalixarene derivative represented by the following formula (2) is also provided.

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3 or 4)

  In the present invention, R is an alkyl group having 1 to 6 carbon atoms (further, an alkyl group having 1 to 4 carbon atoms) from the viewpoint of intramolecular hydrogen bonding interaction with a secondary amino group and steric hindrance. It is preferable. From the viewpoint of producing a cyclic compound having a new inclusion function, R ′ is an acyl group having 1 to 6 carbon atoms (more preferably 1 to 4 carbon atoms), an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythio group. A carbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group is preferred.

(Method for producing azacalixarene derivative (2))
The method for producing the azacalixarene derivative (2) is not particularly limited. From the viewpoint of imparting a new inclusion function to the azacalixarene of the formula (1), the azacalixarene derivative (2) is preferably produced by the following method.

  That is, the following formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4), a substitution reaction or addition in a secondary amino group which is a bridging group of azacalixarene By introducing a substituent into the cross-linking group by carrying out the reaction, the following formula (2):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3 or 4).

(Inclusion complex)
In the present invention, an inclusion complex (also referred to as an “inclusion compound”) including a guest molecule and a host molecule corresponding to the guest molecule can be obtained. As the host molecule, the following formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4), or the following formula (2):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3 or 4).

(Guest molecule)
The guest molecule that can be used in the present invention is not particularly limited as long as it can form an inclusion complex with the azacalixarene (1) or the azacalixarene derivative (2). From the viewpoint of the coordination bond interaction between the amino group of the bridging group and the substituent that can be introduced into the bridging group, the following guest molecules can be suitably used (for details of such guest molecules, If necessary, reference can be made to the literature: Pharmaceutical Journal Vol. 122, 219 (2002)).

Heavy metal ions such as Pd, Pt, Ag, Au, Hg

(Use of inclusion complex)
There are no particular restrictions on the method or field of use of the inclusion complex of the present invention. From the viewpoint of the coordination bond interaction between the amino group of the bridging group and the substituent that can be introduced into the bridging group, it can be suitably used in the following methods and fields (use of such inclusion complexes) For details of the method, reference can be made to the literature: Pharmaceutical Journal Vol. 122, page 219 (2002), if necessary).

  Selective capture and separation of noble or harmful heavy metal ions by organic solvent extraction and separation

  Hereinafter, the present invention will be described more specifically with reference to examples.

トリス（ジベンジリデンアセトン）ジパラジウム０．０５ミリモル（ｍｍｏｌ）、９，９−ジメチル−４，５−ビス（ジフェルニルホスフィイノ）キサンテン０．１ミリモルをトルエン１５ｍｌに溶解し、ナトリウム−ｔｅｒｔ−ブトキシド３ミリモルを加え、更に１，３−ブロモ−４，６−ジメトキシベンゼン１ミリモル、と１，３−フェニレンジアミン１ミリモルを加えて、窒素雰囲気下１００℃の反応温度で５日間反応させた。この場合に用いた反応装置の構成、および他の反応条件は、以下の通りである。 Example 1
(According to the reaction scheme of formula (5))

Tris (dibenzylideneacetone) dipalladium 0.05 mmol (mmol), 9,9-dimethyl-4,5-bis (difernylphosphiino) xanthene 0.1 mmol were dissolved in 15 ml of toluene, sodium-tert -3 mmol of butoxide was added, 1 mmol of 1,3-bromo-4,6-dimethoxybenzene and 1 mmol of 1,3-phenylenediamine were added, and the mixture was reacted at a reaction temperature of 100 ° C. for 5 days in a nitrogen atmosphere. . The configuration of the reactor used in this case and other reaction conditions are as follows.

(Reactor and conditions)
(1) Schlenk tube (25 ml capacity)
(2) Other configurations (magnetic stirrer, stirrer oil bath, condenser, nitrogen line)
(3) Under normal pressure and nitrogen atmosphere

  By the above reaction, azacalixarene, which is a cyclic compound having a secondary amino group as a bridging group, was obtained (by 1,3-bromo-4,6-dimethoxybenzene as a raw material by thin layer chromatography (TLC)). This was confirmed by confirming the disappearance of 1,3-phenylenediamine and the formation of a new compound).

  In order to remove sodium bromide and acyclic compounds which are palladium complexes and by-products from the obtained reaction mixture, the following purification operations (a) to (d) were performed.

(Purification operation)
(I) Wash with aqueous ammonia (29%) and extract with chloroform (b) Wash with ethylenediamine-disodium tetraacetate aqueous solution (c) Separation and purification by column chromatography (silica gel, eluent chloroform) (d) Preparative gel Separation and purification by permeation chromatography

Through the above purification operation, powdered cyclic compound 7 (m = 2), compound 8 (m = 3) and compound 9 (m = 4) represented by the following formula (6) were separately isolated and vacuum-dried.

  The elemental analysis values of the cyclic compound 7 are carbon 68.71%, hydrogen 5.67%, and nitrogen 11.05%. The calculated value of the compound 7 represented by the formula (6) (carbon 69.41%, hydrogen 5 .82%, nitrogen 11.56%). The yields of cyclic compound 7 (m = 2), compound 8 (m = 3) and compound 9 (m = 4) in this example were 7: 19%, 8: 9% and 9: 1%, respectively. It was.

The above cyclic compound 7 (m = 2), compound 8 (m = 3) and compound 9 (m = 4) were soluble in common organic solvents such as chloroform, acetonitrile, tetrahydrofuran and the like. Therefore, when mass spectrometry (FAB-MS) was performed on the cyclic compound 7 (m = 2), the compound 8 (m = 3), and the compound 9 (m = 4), m / z = 485, 727, and 969, respectively. The main peaks are observed, and these data indicate the molecular structures of azacalixarene (m = 2), compound 8 (m = 3) and compound 9 (m = 4) represented by the following formula (6), respectively. It was confirmed that it coincided with the protonated molecular ion peak.

The ¹ H NMR spectra of the cyclic compound 7 (m = 2), compound 8 (m = 3) and compound 9 (m = 4) showed the following signals.

¹ H NMR (in CDCl ₃ ):
Compound 7: 7.28 (s2H) 7.11 (s2H) 7.09 (t2H) 6.55 (s2H) 6.36 (d4H) 5.67 (br4H) 3.79 (s12H).

  Compound 8: 7.32 (s3H) 7.00 (t3H) 6.96 (s3H) 6.53 (s3H) 6.26 (d6H) 5.78 (s6H) 3.78 (s18H).

  Compound 9: 7.27 (s4H) 7.06 (s4H) 6.74 (br4H) 6.46 (br8H) 6.41 (d4H) 5.73 (br8H) 3.78 (s24H).

Example 2

以下に示した反応条件以外は、実施例１と同様に反応を行った。 (According to reaction scheme of formula (7))

The reaction was conducted in the same manner as in Example 1 except for the reaction conditions shown below.

  0.025 mmol of tris (dibenzylideneacetone) dipalladium and 0.05 mmol of 9,9-dimethyl-4,5-bis (difernylphosphiino) xanthene were dissolved in 5 ml of toluene, and sodium-tert-butoxide 1 Then, 0.33 mmol of 1,3-bromobenzene and 0.33 mmol of 4,6-dimethoxy-1,3-phenylenediamine were added, and the reaction temperature was 100 ° C. for 5 days under a nitrogen atmosphere. Reacted. By this reaction, azacalixarene, which is a cyclic compound having a secondary amino group as a crosslinking group, was obtained.

  The subsequent purification operation was performed in the same manner as in Example 1.

  Through the above operation, powdered cyclic compound 7 (m = 2), compound 8 (m = 3) and compound 9 (m = 4) were separately isolated and vacuum-dried. The yields of cyclic compound 7 (m = 2), compound 8 (m = 3) and compound 9 (m = 4) in this example were 7: 23%, 8: 13% and 9: 3%, respectively. .

The above cyclic compound 7 (m = 2), compound 8 (m = 3) and compound 9 (m = 4) are the cyclic compound 7 (m = 2) and compound 8 (m = 3) obtained in Example 1. It was confirmed by elemental analysis, mass spectrometry (FAB-MS), and ¹ H NMR spectrum that it was the same as Compound 9 (m = 4).

Example 3
To the cyclic compound 7 (m = 2) (0.01 mmol) obtained in Example 1, 0.5 ml of acetic anhydride was added and reacted in air at a reaction temperature of 140 ° C. for 4 hours. The precipitate produced by this reaction was filtered off. By washing the obtained powdered solid with water, a cyclic compound 10 (formula (8)) in which the crosslinking group of the cyclic compound 7 (m = 2) was N-acetylated was obtained in a yield of 92%. .

The cyclic compound 10 was soluble in an organic solvent such as chloroform and dichloromethane at a low concentration. When mass analysis (FAB-MS) was performed on the cyclic compound 10, a main peak was observed at m / z = 653, and it was confirmed that the molecular structure of the cyclic compound 10 represented by the formula (8) was matched. It was. The ¹ H NMR spectrum of the cyclic compound 10 (formula (8)) showed the following signal.

¹ H NMR (in CDCl ₃ ): 7.21 (br8H) 6.58 (br4H) 3.89 (br12H) 2.01 (br12H)
These results indicate that the cyclic compound obtained in Example 1 has a reactive secondary amino group as a crosslinking group and can be converted to an N-acetyl derivative by a substitution reaction.

Example 4
Acetic anhydride (0.5 ml) was added to the cyclic compound 8 (m = 3) (0.01 mmol) obtained in Example 1, and reacted in air at a reaction temperature of 140 ° C. for 4 hours. After adding water and stirring, the organic layer was separated. The solvent was distilled off, and separation and purification were performed by column chromatography (silica gel, eluent chloroform / methanol), whereby cyclic compound 11 (formula (9)) in which the crosslinking group of cyclic compound 8 (m = 3) was N-acetylated. ) Was obtained in a yield of 87%.

Said cyclic compound 11 (Formula (9)) was soluble in common organic solvents, such as chloroform, acetonitrile, tetrahydrofuran. When mass spectrometry (FAB-MS) was performed on the cyclic compound 11 (formula (9)), a main peak was observed at m / z = 979, and the molecular structure of the cyclic compound 11 represented by formula (9) It was confirmed that they matched. The ¹ H NMR spectrum of the cyclic compound 11 (formula (9)) showed the following signal.

¹ H NMR (in DMSO, 100 ° C.): 7.31 (br3H) 7.17 (br6H) 7.021 (br6H) 6.85 (s3H) 3.88 (s18H) 1.81 (s18H)

Comparative Example 1
As shown in the following formula, 0.05 mmol of tris (dibenzylideneacetone) dipalladium and 0.1 mmol of 9,9-dimethyl-4,5-bis (difernylphosphiino) xanthene were dissolved in 15 ml of toluene. , Sodium-tert-butoxide (3 mmol), 1,3-bromobenzene (1 mmol) and 1,3-phenylenediamine (1 mmol) were added, and the mixture was reacted at a reaction temperature of 100 ° C. for 5 days in a nitrogen atmosphere. .

  In this reaction, the production of poly (imino-1,3-phenylene) or oligo (imino-1,3-phenylene), which is a linear compound, was confirmed.

In order to remove the palladium complex and by-product sodium bromide and the non-cyclic compound, the following operations (a) and (b) were performed.
(B) Wash with aqueous ammonia (29%) and extract with chloroform (b) Wash with ethylenediamine-disodium tetraacetate aqueous solution

After the above purification operation, the solvent of the organic phase was distilled off and mass spectrometry (FAB-MS) was performed. As a result, a very small peak was observed at m / z = 365. This value agrees with the molecular structure of the cyclic compound 12 represented by the formula (11).

  Therefore, in this reaction, it was confirmed that a cyclic compound having a secondary amino group as a bridging group was produced, but the production amount was extremely small, and isolation production was not achieved.

  This result shows that generation of a chain compound, that is, an acyclic polymer is prioritized, and azacalixarene, which is a cyclic compound having a secondary amino group as a bridging group, is hardly generated. By introducing an alkoxy group having hydrogen-bonding interaction to the base and controlling the three-dimensional structure of the intermediate in the cyclic compound formation process by intramolecular hydrogen-bonding interaction between the secondary amino group and the alkoxy group. This shows that it is possible to produce and isolate a cyclic compound crosslinked with an amino group.

Comparative Example 2
As a method for producing azacalixarene, which is a cyclic compound having a secondary amino group as a bridging group, British Patent GB 998560 (1965) was prepared by reacting resorcinol with 1,3-phenylenediamine in the presence of Na ₂ S ₂ O ₅ . A method for producing the cyclic compound 12 represented by the formula (12) has been proposed.

  The reaction was further tested by the method described in this patent to obtain a brown product. However, when mass spectrometry (FAB-MS) was performed on the obtained product, a signal corresponding to the molecular structure of the cyclic compound 12 represented by the formula (11) was not observed, and the production of the cyclic compound 12 was confirmed. could not.

  According to the present invention, by producing an azacalixarene having a secondary amino group as a crosslinkable group, the crosslinkable group can be made reactive, and various kinds of crosslinkable groups can be added to the crosslinkable group by performing a substitution reaction or an addition reaction. Substituents can be introduced, and a cyclic host molecule that can be used for various purposes can be provided.

  These cyclic compounds are obtained by stereocontrolling a system based on hydrogen-bonding interaction between an alkoxy group and an amino group in a 1,3-dihalogenated benzene and 4,6-dialkoxy-1,3-phenylenediamine (the alkoxy group is Carbon of 1 to 8 carbon atoms) or 1,3-dihalogenated-4,6-dialkoxybenzene and 1,3-phenylenediamine (the alkoxy group represents an alkoxy group of 1 to 8 carbon atoms) -It can manufacture by carrying out a condensation cyclization reaction by nitrogen bond production | generation reaction. These cyclic compounds can be produced and isolated by controlling the steric structure by intramolecular hydrogen bonding interaction between an amino group and an alkoxy group. Since the cyclic compound obtained by this production method has a reactive secondary amino group in the unit skeleton, it can be used as a core molecule that can be arbitrarily converted into various derivatives by substitution and addition reactions. It is possible to provide a cyclic host molecule adapted to the purpose.

Claims (5)

Following formula (1):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4). 1,3-dihalogenated benzene and 4,6-dialkoxy-1,3-phenylenediamine (the alkoxy group is an alkoxy group having 1 to 8 carbon atoms), or
1,3-dihalogenated-4,6-dialkoxybenzene and 1,3-phenylenediamine (the alkoxy group is an alkoxy group having 1 to 8 carbon atoms) are subjected to a condensation reaction in the presence of a palladium complex catalyst. Formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4)
A method for producing an azacalixarene represented by the formula: Following formula (2):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3 or 4). Following formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4), a substitution reaction or addition in a secondary amino group which is a bridging group of azacalixarene By introducing a substituent into the cross-linking group by carrying out the reaction, the following formula (2):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3, or 4), and a method for producing an azacalixarene derivative. An inclusion complex including a guest molecule and a host molecule corresponding to the guest molecule; and the host molecule is represented by the following formula (1):

(Wherein R represents an alkyl group having 1 to 8 carbon atoms, and m is an integer of 2, 3 or 4), or the following formula (2):

(Wherein, R represents an alkyl group having 1 to 8 carbon atoms, and R ′ represents an acyl group, an alkyl group, an aryl group, an alkoxycarbonyl group, an alkoxythiocarbonyl group, a carbamoyl group, a thiocarbamoyl group, or a sulfonyl group. , M is an integer of 2, 3 or 4).