JP2008280269A - Calixarene dimer compound and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new calixarene dimer compound, and a method for producing the compound. <P>SOLUTION: The method for producing the calixarene dimer compound involves a step for reacting resorcinol with 1,6-hexanedial in the presence of an acid catalyst to afford the calixarene dimer. The structure of the calixarene dimer is the one obtained by the dehydration condensation of the 2- and 4-positions of the resorcinol with an aldehyde carbon to crosslink the resorcinol, to thereby dimerize the resorcinol. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a calixarene dimer compound and a method for producing the same.

Cyclic compounds are expected to exhibit properties and functions that are not found in linear compounds. On the other hand, in the conventional synthesis method of cyclic compounds, the synthesis reaction is carried out under diluting conditions, and the process is multi-step. Since there is a problem that a cyclic compound as a synthesis target cannot be obtained in a high yield, research on synthesis methods in addition to its physical properties has been actively conducted.
Thus, in recent years, for example, it is possible to selectively synthesize cyclic compounds using dynamic covalent bonds (covalent bonds governed by equilibrium) such as ester bonds, imine bonds, disulfide bonds, and acetal bonds. It has been reported.

  In addition, the calixarene compound, which is a kind of cyclic compound, is not necessarily required for dilution conditions by performing the synthesis reaction at a high temperature, and a high yield can be obtained. Its reversible reactivity has been pointed out.

  However, the present inventors have also found resorcinol and 1 which have been found by paying attention to a technique for selectively synthesizing a cyclic compound by using a dynamic covalent bond and the reversible reactivity of the calixarene compound. , 5-pentanediar has been proposed to synthesize a macrocyclic compound (named by the inventors as “Noria”). According to this method, the synthesis purpose is as high as 83%. It has been reported that a cyclic compound is obtained (see, for example, Non-Patent Document 1).

H. Kudo, R.A. Hayashi, K .; Mitani, T .; Yokozawa, N .; C. Kasuga, T .; Nishikubo. Angew, Chem, lnt, Ed. , 45, 7948-7852 (2006)

  In the present invention, based on the above circumstances, a cyclic compound can be obtained by reacting resorcinol and 1,5-pentane dial, which is a bifunctional aldehyde, found by the inventors. As a result of repeated research on a method for synthesizing a cyclic compound by reacting resorcinol with a bifunctional aldehyde, the object was completed, and the object was to provide a novel calixarene dimer compound and a method for producing the same Is to provide.

  The calixarene dimer compound of the present invention is represented by the following general formula (1).

[Wherein, R ¹ represents a hydrogen atom or a monovalent organic group. ]

The method for producing a calixarene dimer compound of the present invention is characterized in that a calixarene dimer compound is obtained through a step of reacting resorcinol with 1,6-hexanedial.
In the method for producing a calixarene dimer compound of the present invention, it is preferable to react resorcinol with 1,6-hexane dial in the presence of an acid catalyst.

ADVANTAGE OF THE INVENTION According to this invention, the novel calixarene dimer compound which is a cyclic oligomer which has a calixarene skeleton, and its manufacturing method can be provided.
Moreover, according to the method for producing a calixarene dimer compound of the present invention, a calixarene dimer compound can be easily obtained.

  The calixarene dimer compound of the present invention is a cyclic oligomer having a calixarene skeleton, and is a compound represented by the above general formula (1) (hereinafter also referred to as “specific calixarene dimer compound”).

In the general formula (1) indicating the specific calixarene dimer compound, R ¹ is a hydrogen atom or a monovalent organic group.
Examples of the monovalent organic group representing the group R ¹ include a t-butoxycarbonyl group.

Such a specific calixarene dimer compound is obtained, for example, by undergoing an addition condensation reaction of resorcinol and 1,6-hexane dial in the presence of an acid catalyst (hereinafter also referred to as “addition condensation step”). Can be synthesized.
The synthesis process in the addition condensation step of the specific calixarene dimer compound is shown in the following reaction formula (1).

  In this addition condensation step, the ratio of resorcinol and 1,6-hexanediar used for the reaction is preferably 20: 1 to 20 in terms of molar ratio of the charged amount ratio (resorcinol: 1,6-hexanediar). The charge ratio (resorcinol: 1,6-hexane dial) is particularly preferably 20: 5 to 20: 6.

As the acid catalyst, for example, hydrochloric acid or the like can be used.
The amount of the acid catalyst used is, for example, 1.5 milliliters of 12N concentrated hydrochloric acid in a reaction system of 20 mmol of resorcinol (functional group equivalent 40 mmol) and 1,6-hexane dial 5 mmol (functional group equivalent 10 mmol).

In addition, the reaction represented by the reaction formula (1) relating to the addition condensation step is performed in an appropriate solvent, and as the solvent, for example, ethanol, isopropanol, n-propanol or the like can be used. Ethanol is preferable because a high yield is obtained.
The amount of the solvent used is, for example, 4.5 ml in the reaction system of resorcinol 20 mmol (functional group equivalent 40 mmol) and 1,6-hexane dial 5 mmol (functional group equivalent 10 mmol).

  The reaction temperature is preferably 80 ° C., and the reaction time is preferably 24 hours or more, and particularly preferably 48 hours or more.

  In the above addition condensation step, there are two kinds of compounds as reaction intermediates, which are considered to be a compound represented by the following formula (a) and a compound represented by the formula (b). .

The calixarene dimer compound obtained as the target compound in the addition condensation step has a structure in which R ¹ is a hydrogen atom in the general formula (1) as shown in the reaction formula (1). Since the calixarene dimer compound (hereinafter also referred to as “calixarene dimer compound (1)”) in which R ¹ is a hydrogen atom in the general formula (1) has a hydroxyl group as a reactive group, An appropriate substituent can be introduced as necessary.
Specifically, for example, the introduction of the t-butoxycarbonyl group into the calixarene dimer compound (1) is carried out by using the calixarene dimer compound (1) and di-tert-butyl dicarbonate as tetrabutylammonium bromide as a dissolution accelerator. The substitution reaction can be carried out in the presence of (TBAB) and pyridine as a base. Thereby, the calixarene dimer compound whose R < ¹ > is t-butoxycarbonyl group in General formula (1) can be obtained.
The reaction process of the calixarene dimer compound (1) and di-tert-butyl dicarbonate is shown in the following reaction formula (2).

[Wherein R ² represents a t-butoxycarbonyl group. ]

  Such a specific calixarene dimer compound has a structure formed of 8 equivalents of resorcinol and 4 equivalents of 1,6-hexane dial, and adds resorcinol and 1,6-hexane dial. There is a possibility that a novel cyclic compound obtained by undergoing a condensation reaction step, for example, a compound obtained by introducing a t-butoxycarbonyl group can be used as a resist material.

  And according to the manufacturing method of the specific calixarene dimer compound which has the process of carrying out addition condensation reaction of resorcinol and 1, 6- hexane dial, a specific calixarene dimer compound can be obtained easily.

Further, the calixarene dimer compound in which R ¹ is a hydrogen atom in the general formula (1) obtained in the step of subjecting resorcinol to 1,6-hexanedial has a hydroxyl group as a reactive group Therefore, a substituent can be introduced.

  Hereinafter, specific examples of the present invention will be described, but the present invention is not limited thereto.

In each of the following examples and experimental examples, the following reagents and measuring instruments were used.
(Reagents and solvents)
-Resorcinol, 1, 6-hexanediol, pyridium chromate (PCC), ethanol, 12N hydrochloric acid (HCl), and di-tert-butyl carbonate were used as they were.
-As tetrabutylammonium bromide (TBAB), what was recrystallized using ethyl acetate was used.
-As pyridine, what was distilled and refined in the presence of calcium hydride (CaH ₂ ) after preliminary drying using calcium hydride was used.
(measuring equipment)
Infrared spectrophotometer (IR): Shimadzu Corporation “NICOLET 380 FT-IR” Nuclear magnetic resonance spectrum (NMR): JEOL Ltd. “JNM-ECA-500 type (500 MHz)”, JEOL "JNM-ECA-600 type (600MHz)"
Mass spectrometer (MALDI-TOF-MASS): Shimadzu Corporation “SHIMAZU / KRATOS matrix-assisted laser ionization time-of-flight mass spectrometer KOMPACT MALDI tDE”
Gel permeation chromatography (SEC): Tosoh Corporation “HLC-8220 System”; (Detector) “HLC-8200” built-in RI / UV-8200, (Column) “TSK GEL SUPER AW 3000 × 1 + 2500 × 3”, (Standard) polystyrene, (solvent) DMF (containing 20 mM anhydrous LiBr, 20 mM H ₃ PO ₄ )

[Example 1]
(Synthesis example 1 of 1,6-hexane dial)
As an oxidizing agent, 40 g (180 mmol) of pyridinium chlorochromate (PCC) and 40 g of silica gel (300 mesh) were mixed and pulverized, suspended in 260 ml of methylene chloride, and then 7.2 g of 1,6-hexanediol ( 60 mmol) in 50 ml of methylene chloride was added and stirred at room temperature for 2 hours. After completion of the reaction, 500 ml of diethyl ether was added to this system, and the ether layer was recovered by decanting, and the solvent was distilled off under reduced pressure. Thereafter, silica gel chromatography (developing solvent: ether) was performed, the developing solvent was distilled off under reduced pressure, and then purified by distillation under reduced pressure to obtain 5.3 g of a colorless and transparent liquid with a yield of 74%.

The obtained liquid is 1,6-hexane dial (boiling point: 40.5 to 41.1 ° C. (2.0 mmHg)) represented by the following formula (c) by IR measurement and ¹ H NMR measurement. It was confirmed. The results of IR measurement and ¹ H NMR measurement are shown below.

IR (film, cm ⁻¹ ): 2925, 2853, and 2712 (νC—H), 1730, 1712 (νC═O)
・¹ H NMR (600 MHz, CDCl ₃ , TMS), δ (ppm)
^{1.26 (s, 4.0H, H c} ),
4.17 (m, 4.0H, H ^b ),
^{9.76 (bs, 2.0H, H a} )

(Synthesis Example 1 of calixarene dimer compound)
In a eggplant flask having a volume of 100 ml containing a rotor, 2.2 g (20 mmol: functional group equivalent: 40 mmol) of resorcinol was dissolved in 4.5 ml of ethanol, and 1.5 ml of hydrochloric acid was further added as a catalyst. Under cooling, 0.58 g (5 mmol: functional group equivalent: 10 mmol) of 1,6-hexane dial was added dropwise. Then, a red suspension was obtained by heating in 4.5 ml of ethanol at 80 ° C. for 48 hours. After completion of the reaction, the reaction mother liquor was poured into diethyl ether to precipitate a solid, which was washed with diethyl ether, and then the obtained solid was dried under reduced pressure for 24 hours. .67 g was obtained.

The obtained red solid was confirmed to be a calixarene dimer compound represented by the following formula (1) by IR measurement, ¹ H NMR measurement and mass spectrometry. The results of IR measurement, ¹ H NMR measurement and mass spectrometry are shown below and in FIGS.

Mn: 1800, Mw / Mn: 1.02
IR (film, cm ⁻¹ ): 3269 (νO—H), 2933 and 2859 (νC—H), 1920, 1500, and 1443 (νC = C aromatic)
・¹ H NMR (500 MHz, DMSO-d ₆ , TMS), δ (ppm)
^{1.06~2.35 (b, 32.0H, H a} , H b),
^{4.05~4.22 (m, 8.0H, H c} ),
6.14 (bs, 8.0H, aromatic H e, H h, H i),
6.91 (bs, 8.0H, aromatic H d, H g),
9.13 (m, 16.0H, OH ^f )
Mass spectrometry (MALDI-TOF MS); (matrix: DHBA)
Actual value (m / z) 1195.22 [M + H] ⁺
Calculated value (m / z) 1194.32 [M + H] ⁺

[Examples 2 to 6]
In Synthesis Example 1 of the calixarene dimer compound according to Example 1, the reaction temperature was changed to the temperature shown in Table 1, the solid was precipitated by pouring the reaction mother liquor into diethyl ether, and the obtained solid was taken over 24 hours. A red solid was obtained by drying under reduced pressure.
The crude yield of the product is shown in Table 1 and FIG.

When the obtained red solid was subjected to IR measurement, ¹ H NMR measurement and gel permeation chromatography measurement (SEC measurement (DMF)), a calixarene dimer compound represented by the above formula (1) (calixarene dimer compound (1 )) Was confirmed.
FIG. 5 shows the result of the red fixed SEC measurement.
In FIG. 5, curve (a) is data according to Example 2, curve (b) is data according to Example 3, curve (c) is data according to Example 4, and curve (d) is according to Example 5. Data and curve (e) show data according to Example 6, in each of these curves (a) is a peak derived from calixarene dimer compound and (b) and (c) are reaction intermediates It is a peak derived from.

  By comparing Example 2 to Example 6, when the reaction temperature is low, a large amount of polymer is produced in addition to the synthesis target, but as the reaction temperature increases, the reaction system is present in the reaction system. It was confirmed that the polymer decreased and converged to the calixarene dimer compound (1), which was the synthesis target. Further, it is presumed that the reason why the yield decreases as the reaction temperature increases is that resorcinol is contained in the polymer, and that the content decreases as the reaction temperature increases.

[Examples 7 to 14]
In Synthesis Example 1 of the calixarene dimer compound according to Examples 2 to 6, in the same manner as in Examples 2 to 6, except that the amount of 1,6-hexanedial used was changed to the amount shown in Table 2, A red solid was obtained with the crude yield shown in FIG.
Table 2 and FIG. 6 also show the results of Example 1 for reference.
In FIG. 6, the vertical axis represents the crude yield (%), and the horizontal axis represents the ratio of the charged amount (ratio of charged amount of 1,6-hexanedial to resorcinol).

When the obtained red solid was subjected to IR measurement, ¹ H NMR measurement and gel permeation chromatography measurement (SEC measurement (DMF)), a calixarene dimer compound represented by the above formula (1) (calixarene dimer compound (1 )) Was confirmed.

  By comparing Example 1 and Examples 7 to 14, the ratio of resorcinol and 1,6-hexane dial to be used in the reaction was 20: in the charge ratio (resorcinol: 1,6-hexane dial). It was confirmed that a high yield was obtained when the ratio was 5 to 20: 6.

[Experimental Example 1]
This Experimental Example 1 is an experiment conducted to confirm a preferable solvent in a reaction system for obtaining a calixarene dimer compound.

In an eggplant flask having a volume of 100 ml containing a rotor, 2.2 g (20 mmol: functional group equivalent: 40 mmol) of resorcinol was dissolved in the solvent shown in Table 3 below, and 1.5 ml of hydrochloric acid was further added as a catalyst. Under ice cooling, 5 mmol of a 1,6-hexane dial solution (functional group equivalent: 10 mmol) was slowly added dropwise, and the reaction temperature was 80 ° C. or 90 ° C. in a solvent of 4.5 ml (4.8 mol / L), and the reaction time was 48. The reaction was performed under conditions of time. After completion of the reaction, the reaction mother liquor was poured into methanol, the precipitate was collected by filtration, washed with methanol three times, and the obtained solid was dried under reduced pressure over 24 hours to obtain a red solid.
In addition, methanol used for washing was neutralized with sodium hydrogen carbonate, concentrated under reduced pressure, and poured into ether to obtain a white solid.
Here, the yields of the methanol-insoluble part (red solid) and the methanol-soluble part (white solid) were confirmed by SEC measurement. The results are shown in Table 3, and the results of SEC measurement are shown in FIGS.
In FIG. 7, curve (f) is data relating to a reaction system using ethanol as a solvent, curve (g) is data relating to a reaction system using isopropanol as a solvent, and curve (h) uses n-propanol as a solvent. The data relating to the reaction system at a reaction temperature of 80 ° C. and the curve (i) show the data relating to the reaction system at a reaction temperature of 90 ° C. using n-propanol as the solvent. In each of these curves, (d) Is a peak derived from a polymer other than the calixarene dimer compound that is the synthesis target, (e) is a peak derived from the calixarene dimer compound, and (f) is a peak derived from resorcinol. In FIG. 8, curve (j) is data relating to a reaction system using ethanol as a solvent, curve (k) is data relating to a reaction system using isopropanol as a solvent, and curve (l) is n-propanol as a solvent. The data relating to the reaction system at a reaction temperature of 80 ° C. and the curve (m) show the data relating to the reaction system at a reaction temperature of 90 ° C. using n-propanol as a solvent.

When the obtained red solid was subjected to IR measurement, ¹ H NMR measurement, gel permeation chromatography measurement (SEC measurement (DMF)) and mass spectrometry, it was confirmed that the calixarene dimer compound represented by the above formula (1) was produced. It was done.

  From the above results, when ethanol was used as the solvent, the calixarene dimer compound (calixarene dimer compound (1)) represented by the formula (1), which is the synthesis target, was converted into the calixarene dimer compound (1 ) Is produced more than other polymers (hereinafter also referred to as “other polymers”), but when isopropanol is used, the calixarene dimer compound (1) is hardly produced and other polymers are produced. Many were generated. Moreover, when n-propanol was used as the solvent, the production ratio of the calixarene dimer compound (1) and the other polymer was a value between when ethanol was used and when isopropanol was used. Such a result depends on the polarity of the solvent, and since the dielectric constant decreases in the order of ethanol, n-propanol and isopropanol, when isopropanol having a small polarity is used as the solvent, It is considered that the calixarene dimer compound (1) was hardly produced due to the fact that the polymer was not dissolved but was removed from the system and the equilibrium was tilted toward the other polymer.

[Experiment 2]
This Experimental Example 2 is an experiment conducted to confirm the change over time of the reaction system for obtaining the calixarene dimer compound.

In Synthesis Example 1 of the calixarene dimer compound according to Example 1, the reaction time was changed to 5 minutes, 1 hour, 3 hours, 6 hours, 24 hours and 168 hours (1 week), respectively, and the reaction mother liquor was changed to diethyl Fixation was precipitated by pouring into ether, and the obtained solid was dried under reduced pressure over 24 hours to obtain a red solid.
The obtained red solid was subjected to IR measurement, ¹ H NMR measurement and gel permeation chromatography measurement (SEC measurement (DMF)), respectively. As a result, a calixarene dimer compound represented by the above formula (1) (calixarene dimer compound) was obtained. The generation of (1)) was confirmed. The result of SEC measurement is shown in FIG. FIG. 9 also shows the results of Example 1 for reference.
In FIG. 9, curve (n) is data relating to a reaction system having a reaction time of 5 minutes, curve (o) is data relating to a reaction system having a reaction time of 1 hour, and (p) is data relating to a reaction system having a reaction time of 3 hours. , (Q) is data relating to a reaction system having a reaction time of 6 hours, (r) is data relating to a reaction system having a reaction time of 24 hours, and (s) is data relating to Example 1 (for a reaction system having a reaction time of 48 hours). (Data) and (t) show data related to the reaction system with a reaction time of 168 hours (1 week). In each of these curves, (g) is a peak derived from the calixarene dimer compound, (h) and ( (I) is a peak derived from the reaction intermediate.
Moreover, when the yield in the reaction system of reaction time 168 hours was confirmed, it was 40%.

From the above results, in the initial stage of the reaction, in addition to the calixarene dimer compound (calixarene dimer compound (1)) represented by the above formula (1), which is a synthesis target, as a high molecular weight polymer or reaction intermediate Although a large amount of oligomer was confirmed, it was confirmed that the high molecular weight polymer or oligomer present in the reaction system gradually decreased and converged to the calixarene dimer compound (1) as the reaction proceeded.
Moreover, it was confirmed that two types of reaction intermediates exist.

Example 15
In an eggplant flask having a volume of 5 ml containing a rotor, 0.30 g (0.25 mmol: OH group equivalent 4 mmol) of calixarene dimer compound (1) was charged and 0.065 g (OH group) of tetrabutylammonium bromide (TBAB). The calixarene dimer compound (1) was dissolved by adding 3 milliliters of pyridine together with 5 mol%), and then 1.3 g (6 mmol) of di-tert-butyldicarbonate (DiBoc) was slowly added dropwise under ice cooling. And stirred at room temperature for 24 hours. After completion of the reaction, the mother liquor was diluted with chloroform, washed 3 times with 1N hydrochloric acid and once with tap water, the organic layer was dried with a desiccant composed of anhydrous magnesium sulfate, and the desiccant was filtered off. After concentration, reprecipitation was performed using chloroform as a good solvent and hexane as a poor solvent to obtain 0.37 g of a white solid with a yield of 52%.

The obtained white solid was confirmed by IR measurement and ¹ H NMR measurement to be a calixarene dimer compound in which R ¹ is a t-butoxycarbonyl group in the general formula (1), and the etherification rate was 100%. It was confirmed that. The results of IR measurement and ¹ H NMR measurement are shown below and in FIG. 10 and FIG.

IR (film, cm ⁻¹ ): 2981, 2934, and 2864 (νC—H), 1760 (νC═O), 1615, 1592, and 1497 (νC = C aromatic), 1371 (νt-butyl), 1272 and 1143 (νC) -O-C ether) · ¹ H NMR (500 MHz), DMSO, TMS: δ (ppm)
0.86 to 2.01 (m, 176.0H, t-butyl H, —CH ₂ CH ₂ CH ₂ —),
3.79-4.12 (m, 8.0H,> CH-),
6.81 to 7.13 (m, 16.0H, aromaticH)

1 is an IR spectrum diagram of a calixarene dimer compound according to Example 1. FIG. 1 is a ¹ H NMR spectrum diagram of a calixarene dimer compound according to Example 1. FIG. 3 is data of MALDI-TOF MS measurement (mass spectrometry) of the calixarene dimer compound according to Example 1. FIG. It is a graph which shows the relationship between the crude yield of the calixarene dimer compound which concerns on each of Example 2-Example 6, and reaction temperature. It is the data of the SEC measurement of the calixarene dimer compound which concerns on each of Example 2-Example 6. FIG. It is a graph which shows the relationship between the crude yield of the calixarene dimer compound which concerns on each of Example 1, Example 7-Example 14, and the preparation amount of 1, 6- hexane dial with respect to resorcinol. It is the data of the SEC measurement of the methanol insoluble part which concerns on Experimental example 1. FIG. It is the data of the SEC measurement of the methanol soluble part which concerns on Experimental example 1. FIG. It is the data of the SEC measurement concerning Experimental example 2. 6 is an IR spectrum diagram of the calixarene dimer compound according to Example 15. FIG. 2 is a ¹ H NMR spectrum diagram of a calixarene dimer compound according to Example 15. FIG.

Claims (3)

A calixarene dimer compound represented by the following general formula (1):

[Wherein, R ¹ represents a hydrogen atom or a monovalent organic group. ]   A method for producing a calixarene dimer compound, wherein a calixarene dimer compound is obtained through a step of reacting resorcinol with 1,6-hexanedial.   The method for producing a calixarene dimer compound according to claim 2, wherein resorcinol is reacted with 1,6-hexanedial in the presence of an acid catalyst.

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