JP2000016956A - Production of calix(4)arene derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To selectively produce the subject compound useful as a molecular recognition clathrate compound or the like in high yield by carrying out a condensation reaction through dehydration of phenols with aldehydes in a specific reaction solvent in the presence of an alkali catalyst. SOLUTION: (A) Phenols such as p-tert-butylphenol and (B) aldehydes such as paraformaldehyde are subjected to a condensation reaction through dehydration in (C) a reaction solvent of the formula R4O(R3O)tR5 [R3 is a 2-4C alkylene; R4 and R5 are each a 1-4C alkyl; (t) is >=1], preferably a glycol diether-based high boiling point solvent having >=180 deg.C boiling point (e.g. triethylene glycol dimethyl ether) in the presence of (D) an alkali catalyst such as potassium hydroxide, preferably for 3-10 hr while heating and refluxing the reaction mixture to provide the objective compound of the formula [R1 and R2 are each H, an alkyl or the like; (m) is 0-4], [e.g. n-tert-butylcalix(4)arene].

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a calixarene derivative. More specifically, the present invention relates to a method for producing a calix (4) arene compound used for the development of new functions such as molecular recognition in a high yield and high selectivity.

[0002]

2. Description of the Related Art Calixarene compounds (derivatives) are known as compounds having a cylindrical structure similar to cyclodextrin. Numerous studies and application developments utilizing such structural characteristics and functions (inclusion function, catalyst function, etc.) have been conventionally performed.

[0003] Those utilizing functions are known as enzymatic reactions, catalytic reactions, metal ion transporters and selective adsorbents, or as clathrates for molecular recognition. For example, in the field of electrophotography, a toner for developing an electrostatic image containing a calix (n) arene compound as a negative charge control agent (JP-A-2568675, JP-A-7-64336). Japanese Patent Application Laid-Open No. 10-48858) and an electrophotographic photoreceptor containing azotized calix (n) arene.

[0004] A method for synthesizing a calixarene compound is described in J. Am. Am. Chem. Soc. 1981,
103, 3782-3792 (CD Gutsche)
et al), Org. Synth. (1990),
68, 234-237 (CD Gutschet et al.
al), generally, phenols and formaldehyde are reacted with an aromatic solvent such as xylene as a reaction solvent in the presence of a base catalyst such as KOH, NaOH, or tert-butyl alkoxide (tert-BuOK). The crude product is synthesized in a one-step method by dehydration-condensation under the following conditions, purified using a solvent such as chloroform, and, if necessary, separated by chromatography to obtain the desired product.

[0005] Am. Chem. Soc. 1989,
111, 8192 use tetralin as a reaction solvent for the synthesis of p-ter-butylcalix (5) arene. Macromol. Chem. R
rapid Commun. 3,705 (1982) uses 1,4-dioxane as a reaction solvent for the synthesis of p-ter-butylcalix (7) arene. J. Org. Chem. 1977, 42, 3
82, J.A. Org. Chem. 1978, 43, 428
For the synthesis of p-ter-butylcalix (4) arene, a water-insoluble high-boiling solvent such as tetralin or diphenyl ether is used as a reaction solvent. A method for purification using a solvent is described.

Japanese Unexamined Patent Publication (Kokai) No. 59-104331 relates to a method for producing a hexacyclic phenol / formaldehyde compound, and relates to a phenol / formaldehyde resin obtained by reacting a p-phenylphenol with formaldehyde (a phenol-formaldehyde resin). Methylolated oligomer)
A method is described in which a non-aqueous solvent (for example, toluene, xylene, heptane, dioxane, etc.) and a hydroxide of K or Rb are added, and the mixture is heated and reacted. A similar method is also applied to a 7-ring and an 8-ring, as disclosed in
-104332 and JP-A-59-104333.

However, the crude synthetic calix (n) arene derivative obtained by the conventional method often contains an acyclic compound or a cyclic compound having a different degree of cyclization.
Therefore, a large amount of solvent is required for purifying the crude synthetic product. In addition, in order to selectively isolate only the desired calix (n) arene from the crude synthetic product or to extract it with high purity, a harmful solvent such as chloroform is required and the yield is reduced. Manufacturing is disadvantageous due to high costs.

The present invention has been made to solve the above-mentioned problems in the prior art, and an object of the present invention is to selectively produce a calix (4) arene derivative in a high yield. It is to provide a method.

[0009]

According to the process for producing a calix (4) arene derivative of the present invention, a phenol and an aldehyde are dehydrated and condensed in a reaction solvent in the presence of an alkali catalyst to obtain a compound represented by the following general formula (I): A method for producing a calixarene derivative represented by the formula: wherein the reaction solvent is a glycol diether-based high-boiling solvent. General formula (I)

[0010]

Embedded image [In the general formula (I), R ¹ and R ² each represent hydrogen, a linear or branched alkyl group, an alkenyl group, an unsubstituted or substituted phenyl group, an alkoxy group, an alkoxyalkyl group, an alicyclic group, Or an unsubstituted or nuclear-substituted aralkyl group, and R ¹ and R ² may be the same or different. M represents an integer of 0 to 4. In addition, the bonding order of the structural unit containing R ¹ and the structural unit containing R ² is arbitrary. The reaction solvent in the present invention is preferably a glycol diether-based high-boiling solvent represented by the following formula (A). Formula (A) R ⁴ O (R ³ O) _t R ⁵ [In the formula (A), R ³ represents an alkylene group having 2 to 4 carbon atoms, and R ⁴ and R ⁵ each independently represent a 1-carbon atom. To 4
And t represents an integer of 1 or more. The boiling point of the glycol diether-based high boiling point solvent is preferably 170 ° C. or higher from the viewpoint of selectivity and yield in producing the calix (4) arene derivative. Particularly preferably, it is 180 ° C. or higher.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS In the production method of the present invention, a glycol diether-based high-boiling solvent (preferably having a boiling point of 18
0 ° C. or more) in the presence of an alkali catalyst (preferably an alkali metal hydroxide) in the presence of an aldehyde (preferably formaldehyde) with one or two phenols represented by the following formula (B). By doing so, a calixarene derivative represented by the following general formula (I) can be produced. This dehydration condensation can be performed under heating and reflux. According to the production method of the present invention, only the calix (4) arene derivative can be obtained in a high yield by the one-step method.

[0012]

Embedded image Formula (B) [In the formula (B), R is hydrogen (H), a linear or branched alkyl group, an alkenyl group, an unsubstituted or substituted phenyl group, an alkoxy group, an alkoxyalkyl group, an alicyclic group, or Indicates an unsubstituted or nuclear-substituted aralkyl group. Examples of the phenols used as the main raw material in the method for producing the calix (4) arene derivative of the present invention include the following. That is, phenol wherein R in the formula (B) is hydrogen; R in the formula (B) is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a tert-butyl group,
Straight-chain or branched-chain alkyl groups such as amyl group, isoamyl group, tert-amyl group, hexyl group, isohexyl group, 2-ethylhexyl group, octyl group and tert-octyl group (for example, those having 1 to 12 carbon atoms). , P
Alkyl phenols; R in the formula (B) is an alkenyl group such as an allyl group, a propenyl group, an isopropenyl group, a 1-butenyl group, a 2-butenyl group, a 3-butenyl group (for example, one having 1 to 12 carbon atoms); Wherein R in the formula (B) is an alkyl group having 1 to 4 carbon atoms such as a methyl group or an ethyl group; an alkoxy group having 1 to 4 carbon atoms such as a methoxy group or an ethoxy group; P-phenylphenols which are phenyl groups which are nucleus-substituted or unsubstituted with a group, halogen or the like; R in the formula (B) is a methoxy group, an ethoxy group, an isopropoxy group,
Alkoxy groups such as butoxy groups (for example, having 1 to 12 carbon atoms)
R in the formula (B) is an alkoxyalkyl group (for example, having 1 to 12 carbon atoms) such as a methoxyethyl group, an ethoxypropyl group, and an octoxypropyl group. , P-alkoxyalkylphenols; R in formula (B)
Is an alicyclic group (cycloalkyl group, for example, having 3 to 12 carbon atoms) such as a cyclopentyl group, a cyclohexyl group, or a cyclooctyl group; a p-alicyclic group-substituted phenol; Is an aralkyl group such as a benzyl group, a phenylethyl group, an α, α′-dimethylbenzyl group; an alkyl group having 1 to 4 carbon atoms such as a methyl group or an ethyl group; And p-aralkylphenols which are aralkyl groups whose nucleus is substituted with an alkoxy group, nitro group, halogen or the like.

One or two of these phenols can be used, and form a main constituent of the calix (4) arene represented by the general formula (I).

Calix (4) represented by the general formula (I)
The arene has, for example, the following structure.

Specifically, for example, it has the following structure.

[0016]

Embedded image [P-tert-butyl calix (4) arene]

[0017]

Embedded image [R ¹ : tert-butyl group, R ² : phenyl group, m is 0
The bonding order of the structural unit containing a tert-butyl group and the structural unit containing a phenyl group is an arbitrary integer. Examples of aldehydes that link phenols by dehydration condensation with phenols include formaldehyde (paraformaldehyde), acetaldehyde, cyclohexylaldehyde, benzaldehyde, and the like. Generally, paraformaldehyde which generates formaldehyde is used.

Aldehydes such as paraformaldehyde are generally used in an amount of 1 to 1.5 equivalents to phenols.

In the method for producing a calix (4) arene derivative of the present invention, the dehydration condensation reaction of phenols and aldehydes is carried out by an alkali catalyst, that is, KOH, Na
OH, RbOH, alkali metal hydroxides or metal alkoxides such as LiOH _{(e.g., tert-C 4 H 9 OK} )
(Particularly a strong base containing an alkali metal). The alkali catalyst is usually used in an amount of 0.1 to phenols.
It is used in an amount of from 01 equivalent to 0.05 equivalent. In this reaction, an alkali metal ion (K ⁺ ,
It is believed that ring formation proceeds by the template effect of Na ⁺ , Rb ⁺ , Li ^+, etc.).

A feature of the present invention resides in that a glycol diether-based high-boiling solvent is used as a reaction solvent. Preferred are glycol diether-based high-boiling solvents represented by the following formula (A). Formula (A) R ⁴ O (R ³ O) _t R ⁵ [In the formula (A), R ³ is an alkylene group having 2 to 4 carbon atoms (eg, an ethylene group, a propylene group, a trimethylene group, a 1,2-butylene) Group, 1,3-butylene group, 2,3
-Butylene group), and R ⁴ and R ⁵ each independently represent an alkyl group having 1 to 4 carbon atoms (eg, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, etc.), and t is It represents an integer of 1 or more (preferably an integer of 2 to 10, more preferably an integer of 2 to 5). Specific examples of the glycol diether-based high boiling solvent represented by the formula (A) include diethylene glycol dimethyl ether (diglyme), triethylene glycol dimethyl ether (triglyme), tetraethylene glycol dimethyl ether (tetraglyme), and polyethylene glycol dimethyl ether (t Is a mixture of two or more polyglymes), diethylene glycol diethyl ether, triethylene glycol diethyl ether, tetraethylene glycol diethyl ether, diethylene glycol methyl ethyl ether,
(Poly) ethylene glycol dialkyl ethers such as diethylene glycol dipropyl ether and diethylene glycol dibutyl ether; (poly) propylene glycol dialkyl such as dipropylene glycol dimethyl ether, dipropylene glycol diethyl ether, tripropylene glycol dimethyl ether, and tripropylene glycol diethyl ether Ethers;
And the like.

These glycol diether-based high boiling solvents can be used alone or as a mixture of two or more.

The glycol diether-based high boiling point solvent is preferably one having a boiling point of 170 ° C. or higher, and particularly preferably one having a boiling point of 180 ° C. or higher (eg, triethylene glycol dimethyl ether (triglyme), diethylene glycol diethyl). Ether, tripropylene glycol diethyl ether).

The cyclization reaction of calix (4) arene is as follows:
In general, the cyclization reaction of calix (6) arene or calix (8) arene proceeds at a higher temperature and gives a higher yield. Of course, in the cyclization reaction of calix (4) arene in glycol diether solvent, calix (4) arene and calix (n) arene having different degrees of condensation differ from glycol diether solvent. The difference in solubility becomes remarkable, and the selectivity of calix (4) arene is good.

The glycol diether solvents are often miscible with water and generally have low toxicity. When a glycol diether solvent having a high boiling point is used, a condensation reaction at a high temperature is possible, and the solvent can be removed by washing with water or the like, and handling is safe.

On the other hand, when a cyclization reaction is carried out using an ether solvent such as water-insoluble diphenyl ether (bp. 259 ° C.) or water-soluble 1,4-dioxane (bp. 101.1 ° C.) as a reaction solvent, Target calix (4)
The arene yield is as low as 20-30%.

The amount of the glycol diether high boiling solvent used as the reaction solvent is 200 per mole of phenols.
The weight is preferably about 400 g, but is not particularly limited.

In the present invention, a dehydration-condensation reaction and a cyclization reaction are carried out using the above-mentioned reaction base material, glycol diether-based high-boiling solvent, and alkali catalyst.

The dehydration condensation reaction and the cyclization reaction are carried out at a boiling point or reflux temperature of the glycol diether-based high boiling solvent used.
For 10 to 10 hours, the water accompanying the dehydration reaction may be distilled out of the system together with a part of the solvent.
After completion of the condensation cyclization reaction, the reaction solution is radiated to room temperature, and then dispersed in an alcohol such as isopropanol.
The precipitate is collected by filtration, and the filtered product is washed with isopropanol, further washed with water, and then dried to obtain a calix (4) arene derivative.

As a typical embodiment of the production method of the present invention, an alkali metal hydroxide (for example, KOH) in a glycol diether-based high-boiling solvent (for example, triglyme) is used.
And the paraformaldehyde is dehydrated and condensed under heating to reflux in the presence of a compound (B), whereby the desired calix (4) arene derivative is obtained in a substantially one-step method. Only in a high yield.

The embodiments of the present invention include a method as in Examples 1 to 3 using one kind of phenol and a method as in Example 4 using two kinds of phenols.

Further, a more specific example of the production method of the present invention is as follows. That is, in 100 to 200 g of triglyme, one or two phenols 0.45
mol, paraformaldehyde 0.58 mol, 10N
Potassium hydroxide (KOH: 0.02 mol) was charged,
After mixing and heating, the mixture is subjected to a dehydration condensation reaction under heating and refluxing for 3 to 10 hours. After the reaction solution was radiated, the product was filtered, and the collected product was washed with isopropanol, further washed with water, and dried to obtain only the desired calix (4) arene. Rate (70% or more).

The confirmation of the product can be carried out by HPLC (high performance liquid chromatography) analysis, MS (mass spectrum) analysis or the like.

[0033]

According to the production method of the present invention, a calix (4) arene derivative can be obtained selectively and at a high yield. The desired product can be obtained in a single pot, and the need for purification or chromatographic separation with a harmful chlorine-based solvent such as chloroform after the reaction is low, so the operation is simple and environmental pollution is not likely to occur, and the production cost is low. Can also be reduced. In addition, high purity calix (4)
Since the arene derivative can be provided, the marketability is enhanced, and it is possible to contribute to the development and application development of a new material using the calix (4) arene derivative.

[0034]

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

Example 1 Using a 1000 ml glass four-necked flask equipped with necessary equipment such as a stirrer and a reflux tube, 150 g of triethylene glycol dimethyl ether (triglyme b
p. 216 ° C.), 67.5 g (0.45 mol) of p-tert-butylphenol, 21.9 g (0.58 mol) of paraformaldehyde, and 2.0 g of 10 N potassium hydroxide (KOH: 0.02 mol) were mixed and mixed. After heating, the mixture was reacted under reflux for 4 hours while partially distilling off a solvent containing water generated by condensation, and then radiated. The reaction solution was dispersed in isopropanol, the precipitate was collected by filtration, and the filtered product was washed with isopropanol, further washed with water, and dried to obtain 56.0 g of a white powder ( (Yield 76.7%)
Of p-tert-butylcalix (4) arene.

The calixarene obtained was analyzed by FD (Fi
eld Desorption) -MS analysis results in FIG.
(The horizontal axis is M / Z, and the vertical axis is the relative abundance [Relative
Abundance]). As a result of FD-MS analysis, it was confirmed that p-tert-butylcalix (4) arene [M / Z 649 (M +)] was obtained with high selectivity.

Example 2 The same procedure and operation as in Example 1 were carried out except that the reaction time was changed to 8 hours in place of triglyme in Example 1 and diethylene glycol diethyl ether (bp. 189 ° C.). 57.3 g of p-tert as powder
-Butyl calix (4) arene was obtained in a yield of 78.5%.

FD-MS of the obtained calixarene
The analysis results were the same as in Example 1, and it was confirmed that p-tert-butylcalix (4) arene was obtained with high selectivity.

Example 3 76.5 g of p-phenylphenol (0.45 mol)
l), 21.9 g of paraformaldehyde (0.58 mol)
l) and 2.0 g of 10N potassium hydroxide (KOH:
0.02 mol) in 200 g of tripropylene glycol dimethyl ether (bp. 215 ° C.)
After refluxing, the mixture was reacted for 7 hours while partially distilling off a solvent containing water generated by condensation, and then radiated. The reaction solution was dispersed in isopropanol, the precipitate was collected by filtration, and the filtered product was washed with isopropanol, further washed with water, and dried to obtain 59.2 g of a white powder ( (72.3% yield) p-phenylcalix (4) arene [confirmed by FD-MS analysis]
I got

Example 4 33.8 g (0.23 g of p-tert-butylphenol)
mol), 46.4 g of p-octylphenol (0.2
3mol), 21.9 g (0.5 mol) of paraformaldehyde
8 mol) and 2.0 g of 10N potassium hydroxide (KO
H: 0.02 mol) in 200 g of dipropylene glycol dibutyl ether (bp. 230 ° C.), and reacted under reflux for 3 hours while partially distilling off a solvent containing water generated by condensation. Dissipated heat. The reaction solution was dispersed in isopropanol, and the precipitate was collected by filtration. The filtered product was washed with isopropanol, further washed with water, and dried to give 64.1 g of a white powder ( A calix (4) arene (derivative) mixture having a yield of 73.3%) was obtained.

The calixarene obtained was obtained from FD-M
The S analysis confirmed that the calix (4) arene represented by the following formula was a mixture of calix (4) arenes in which m was an integer of 0 to 4. The FD-MS analysis results are shown in FIG. 2 (the horizontal axis is M / Z, and the vertical axis is relative abundance [Rela
active Abundance]) and Table 1.

[0042]

Embedded image [In the above formula, the bonding order of the structural unit containing a tert-butyl group and the structural unit containing an octyl group is arbitrary. ]

[0043]

[Table 1] Comparative Example 1 p-tert-butylphenol 67.5 g (0.45
mol), 47.0 g of 37% formalin (HCOH:
0.58 mol), and 2.0 g of 10N potassium hydroxide
(KOH: 0.02 mol) was heated at 110 ° C for 2 hours, and then cooled to obtain a white solid (linear oligomer). This was taken out and pulverized in a mortar and poured into 250 g of diphenyl ether (bp. 259 ° C.), and reacted under reflux for 5 hours while partially distilling off a solvent containing water generated by condensation. After allowing the reaction to dissipate heat, it is filtered,
The product obtained by filtration was washed with ethanol and dried to obtain 38 g of a crude product. This was purified using hot toluene to give 19.9 g (yield 2) as a white powder.
7.3%) of p-tert-butylcalix (4) arene.

Comparative Example 2 33.8 g of p-tert-butylphenol (0.23
mol), 46.4 g of p-octylphenol (0.2
3 mol), 47.0 g of 37% formalin (HCOH:
0.58 mol), and 2.0 g of 10N potassium hydroxide
(KOH: 0.02 mol) was heated at 110 ° C. for 3 hours, and then cooled to obtain a white solid (linear oligomer). This was taken out and pulverized in a mortar, poured into 300 g of diphenyl ether, and reacted under reflux for 8 hours while partially distilling off a solvent containing water generated by condensation. After the heat was released, the mixture was filtered, and the filtered product was washed with ethanol and dried to obtain 43 g of a crude product. This was purified using hot toluene to obtain 20.3 g (yield: 23.2%) of a calix (4) arene (derivative) mixture composed of two phenol components as a white powder.

The above Examples and Comparative Examples are summarized in Table 2.

[0046]

[Table 2]

[Brief description of the drawings]

FIG. 1 shows an FD-MS spectrum of p-tert-butylcalixarene obtained in Example 1.

FIG. 2 shows an FD-MS spectrum of the calixarene derivative obtained in Example 4.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) // C07B 61/00 300 C07B 61/00 300

Claims (3)

[Claims] A method for producing a calixarene derivative represented by the following general formula (I) by subjecting a phenol and an aldehyde to a dehydration condensation reaction in the presence of an alkali catalyst in a reaction solvent, wherein the reaction solvent is A process for producing a calix (4) arene derivative, which is a glycol diether-based high boiling solvent. General formula (I) [In the general formula (I), R ¹ and R ² each represent hydrogen, a linear or branched alkyl group, an alkenyl group, an unsubstituted or substituted phenyl group, an alkoxy group, an alkoxyalkyl group, an alicyclic group, Or an unsubstituted or nuclear-substituted aralkyl group, and R ¹ and R ² may be the same or different. M represents an integer of 0 to 4. In addition, the bonding order of the structural unit containing R ¹ and the structural unit containing R ² is arbitrary. ] 2. The method for producing a calix (4) arene derivative according to claim 1, wherein the reaction solvent is a glycol diether-based high boiling point solvent represented by the following formula (A). Formula (A) R ⁴ O (R ³ O) _t R ⁵ [In the formula (A), R ³ represents an alkylene group having 2 to 4 carbon atoms, and R ⁴ and R ⁵ each independently represent a 1-carbon atom. To 4
And t represents an integer of 1 or more. ] 3. The method for producing a calix (4) arene derivative according to claim 1, wherein the glycol diether high boiling solvent has a boiling point of 180 ° C. or higher.