JPS6025415B2 - Cyclohexanecarboxylic acid derivative clathrate composition and method for producing the same - Google Patents

Description

[Detailed description of the invention]

The present invention provides a package in which a cyclohexanecarboxylic acid derivative represented by the following general formula m] [wherein R is hydrogen or a lower alkyl group] is added to a metacyclophane represented by the following general formula [1]. Compositions, methods of making the same, and inclusion compositions were utilized. The present invention relates to a method for separating a cyclohexanecarboxylic acid derivative from a mixture containing the cyclohexanecarboxylic acid derivative. In the present invention, the cyclohexanecarboxylic acid derivative [D] means cyclohexanecarboxylic acid and its lower alkyl ester, and the lower alkyl esters include methyl ester, ethyl ester, n-propyl ester, isopropyl ester, and n-butyl ester. , isobutyl ester, tertiary butyl ester, amyl ester, isoamyl ester, etc. These cyclohexanecarboxylic acid derivatives [D] can be synthesized by reacting cyclohexanecarboxylic acid with the corresponding alcohol using an acid or alkali in a conventional manner, or by catalytic reduction of the corresponding benzoate ester. It can also be synthesized and is considered useful as a synthetic intermediate for pharmaceuticals, etc. These cyclohexanecarboxylic acid derivatives

When [0] is synthesized by catalytic reduction, there are disadvantages such as difficulty in separating it from the corresponding benzoic acid ester, which is a raw material for synthesis, by distillation. The present inventors have intensively investigated an effective separation method for the cyclohexanecarboxylic acid derivative m], and have found that the metacyclophane represented by the above formula [1]
1] is a cyclohexanecarboxylic acid derivative

Forms an inclusion composition selectively with [0], thus forming a cyclohexanecarboxylic acid derivative

[0] Cyclohexanecarboxylic acid derivative from the mixture containing

We have discovered that it is possible to separate [0] from other mixtures, and have arrived at the present invention. That is, the present invention provides metacyclophane represented by the above formula [1] with a cyclohexanecarboxylic acid converter.

[0] is a wrapped composition containing a metacyclophane represented by the above formula [1] and a cyclohexanecarboxylic acid derivative.

A cyclohexanecarboxylic acid derivative [B] is brought into contact with the metacyclophane [1] and a mixture containing [0].
This is a method for producing a warm composition containing the metacyclophane [1], further comprising contacting the metacyclophane represented by the formula [1] with a mixture containing the cyclohexanecarboxylic acid derivative [D]. Cyclohexanecarboxylic acid converter

[0] is formed into an enveloping composition, and then the Danenakuaya composition is separated, and the cyclohexanecarboxylic acid derivative is extracted from the enclosing composition.

Cyclohexanecarboxylic acid converter characterized by separating and recovering [0]
This is a method for separating a cyclohexanecarboxylic acid derivative [B] from a mixture containing [0]. In the present invention, the cyclohexanecarboxylic acid derivative [b] can be selectively encased in the metacyclophane [1], and based on this phenomenon, the cyclohexanecarboxylic acid derivative [b] can be wrapped around the metacyclophane [1].

[0] Cyclohexanecarboxylic acid derivative from the mixture containing

[0] can be separated with high selectivity and recovery rate. The present invention will be explained in detail below. The metacyclophane of the present invention may be a cyclic compound represented by the above formula [1], and it can be obtained by various production methods. For example, the manufacturing methods include (a) Helvetica. Chimica Ac.
ta) Volume 50 F is c to mountain US7 (1967) No. 20
4{b) Synthesis (S skin thesis) 424 (19
74) etc. In the present invention, various methods can be applied to obtain a packaged composition of the metacyclophane of the general formula [1] and the cyclohexanecarboxylic acid promoter [m]. For example, cyclohexanecarboxylic acid converter

The metacyclophane [1] may be added to the mixture containing [0], or the mixture obtained by adding the metacyclophane [1] as described above may be used to complete the envelopment. It can also be obtained by overflowing to obtain a completely dissolved solution, cooling this and separating the resulting crystals. Metacyclophane [1] can be easily obtained by any method.
to cyclohexanecarboxylic acid

A capsular composition in which [0] is included can be obtained. The amount of metacyclophane of the above formula [1] is cyclohexanecarboxylic acid derivative

[0]
Cyclohexanecarboxylic acid derivative in the containing mixture

[0]
0.001 to 100 mol, preferably 0.001 to 100 mol per mol.
Preference is given to proportions of from 0.01 to 50 mol, especially from 0.05 to 20 mol. As described above, a cyclohexanecarboxylic acid derivative was added to metacyclophane [1].

When including [0], generally -5
0-35 ○, preferably 0-200 ○, especially 20-
It is carried out at a temperature in the range of 150 qo. The encapsulated composition thus formed is usually separated from the mixture containing it by solid-liquid separation (e.g., furnace separation, deep-D separation, sedimentation, etc.) or by evaporation of the solvent component by distillation. It is suitable for use. In either method, the operating temperature is -50 to 120°C, preferably in the range of 0 to 9 degrees Celsius. In the present invention, "cyclohexanecarboxylic acid derivative [D] is separated from cyclohexanecarboxylic acid derivative [D]"

[0] A mixture containing benzoic acid derivatives is a mixture with a benzoic acid derivative. In this case, by adding metacyclophane to this mixture and encapsulating it, benzoic acid derivatives can be easily converted into cyclohexanecarboxylic acid derivatives [ D] A composition can be obtained in which the encapsulant composition can be separated and the encapsulant ratio (encapsulant component nometacyclophane) is 0.1 to 2.0 hol'mol. Metacyclophane [1] In addition to its performance as mentioned above, it also has the advantage of being able to be synthesized at low cost and the ability to freely select pharmaceutical processes, making it an extremely advantageous process from an industrial perspective. In addition, metacyclophane [1] and the above formula

A packaging composition containing the cyclohexanecarboxylic acid derivative represented by [0] can be easily prepared by various methods. hexanecarboxylic acid derivatives

[0] can be attached and detached,
Pure cyclohexanecarboxylic acid derivative

[0] can be obtained. In the present invention, metacyclophane [1] and cyclohexanecarboxylic acid derivative

Cyclohexanecarboxylic acid derivative from the enveloping composition with [0]

In the case of separating [0], various methods are adopted, but for example, the 'a-enveloping composition is separated from 90 to 350 qo, preferably from 120 to 2
cyclohexanecarboxylic acid derivative by heating to a temperature in the range of 80 qo.

One method for separating [0] is to separate the cyclohexanecarboxylic acid derivative [B] by exposing the encapsulated composition {b} to a solvent such as n-hexane, benzene, cyclohexane, acetone, etc. Advantageously applied. The following is an explanation of the wrapped product of the present invention. After washing the separated crystals (wrapping composition) with inpropyl alcohol, etc., vacuum drying to remove deposits, the analysis results are as follows. Met. '11 Infrared spectroscopy●Metacyclophane; 3050-2850, 1610, 1590, 1490,
1445, 108089 stop 790 70u [Adversary-1]
・Cyclohexanecarboxylic acid: 3200-2400, 1
700, 1450, 1420, 1310, 126Q 1
210.1140.950-920.895.735 [
-・]●Metacyclophane-cyclohexanecarboxylic acid clathrate composition; 3050-2840, 1710, 161
0, 1590, 1490, 1445108089○80
0 70 [Skin-1] Cyclohexanecarboxylic acid ethyl ester: 2960-2840, 1730, 1445
, 1370, 1310, 124fu 116fu 1130,
1040, [enemy-1]●Metacyclophane-cyclohexanecarboxylic acid ethyl ester packaging composition; 3050~
2840, 1733, 1610, 1590, 1490,
1445 1310, 1250, 1180, 1080,
1040, 890, 800700 [Ka-1] Cyclohexanecarboxylic acid normalp. Pyl ester; 2950-2840, 1730, 144
5, 1310, 1245, 116fu113 [Melon-1]
●Metacyclophane-cyclohexanecarboxylic acid normal propyl ester capsule composition: 3050-2840,
1735, 1610, 1590, 1490, 1445,
1310, 1250, 1180, 1085, 890, 8
00, 70u [v-1] Cyclohexanecarboxylic acid isoptyleste/shi; 2920-2840, 1730,
1465, 1445, 1380, 13Iu 124Q
I16fu 1I30・I035 [Ki-1]●Metacyclophane-cyclohexanecarboxylic acid isobutyl ester encapsulated composition: 3050-2840, 1735, 1610
, 1590, 1490, 14451310, 124fu
li75 1140, 1080, 1040, 89u 8
0 Stop 700・[Oi-1]'2} Gas chromatogram analysis The crystals of each envelope composition were mixed with "Silicone OV-1" (manufactured by Nippon Chromato Kogyo) whose main component is dimethyl silicone polymer. “Anachrom-Q” ■ [manufactured by Nippon Chromato Industries ■] whose main phase is diatom ±
As a result of analysis by gas chromatography using a 2-layer column using 3% of cyclohexanecarboxylic acid as a packing material, peaks of cyclohexanecarboxylic acid derivatives were confirmed in each case. Quantitative analysis of the mixture of cyclohexanecarboxylic acid ester and benzoic acid ester and the composition thereof after encapsulating metacyclophane was also carried out using the same gas chromatogram apparatus. As a result, even if the cyclohexanecarboxylic acid ester mixture contains one or more components other than cyclohexanecarboxylic acid ester in any proportion, the encapsulating composition of the present invention can be obtained, and this means that This shows that by using metacyclophane, cyclohexanecarboxylic acid ester can be selectively included and separated from a cyclohexanecarboxylic acid ester-containing mixture. The present invention will be described in detail below with reference to Examples. Note that the selectivity 3 (Kyo) in Examples is a value calculated based on the following formula. 〃2〒) Solid (No.) liquid (where C, /C2 represents the molar ratio of components 1 and 2) Example 1 [Metacyclophane-cyclohexanecarboxylic acid inclusion composition] Cyclohexanecarboxylic acid 2. A mixture of the base and 0.1 part of metacyclophane was heated at 1100C for 5 minutes and then cooled to precipitate white crystals. The crystals were heated in a furnace, washed with 30 parts of inpropyl alcohol, and sufficiently dried under reduced pressure to obtain 0.06 part of white crystals. (mp.128-133oo). The infrared analysis of this enveloping composition was as described above, and it was a holy holy day. It showed absorption at -1 of 1716. Example 2 [Metacyclophane-cyclohexanecarboxylic acid ethyl ester encapsulated composition] A mixture of two cyclohexanecarboxylic acid ethyl esters and 0.1 part of metacyclophane was heated at 110 oo for 5 minutes and then cooled to form white crystals. It precipitated. The crystals were filtered, washed with 3 parts of inpropyl alcohol, and thoroughly dried under reduced pressure to obtain 0.07 parts of white crystals (mp 122-1270). The infrared spectroscopy results of this Baojo composition are as described above, and the result is Shikisei. It showed absorption in 1735-1. Example 3 [Metacyclophane-cyclohexanecarboxylic acid n-propyl ester inclusive composition] A mixture of 20 parts of cyclohexanecarboxylic acid n-propylester and 0.1 part of metacyclophane was heated at 110 qo for 5 minutes, and then Upon cooling, white crystals precipitated. 0.05 part of this crystal was obtained (mp 124-128°C).
The results of infrared analysis of this crystal are as described above, and it is a holy saint.
It showed absorption at 173&ka-1. Example 5 [Separation of cyclohexanecarboxylic acid ethyl ester from a mixture of cyclohexanecarboxylic acid ethyl ester and benzoic acid ethyl ester] 5 parts of a 1:1.25 mixture of cyclohexanecarboxylic acid ethyl ester and benzoic acid ethyl ester and 0.3 parts of metacyclophane were added. After heating at 110 oo for 5 minutes and cooling, white crystals precipitated.

Claims (1)

[Claims] 1 Metacyclophane represented by the following formula [I] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Represented by the following formula [II] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [Provided formula R is hydrogen or a lower alkyl group] An inclusion composition containing a cyclohexanecarboxylic acid derivative. 2 Metacyclophane represented by the following general formula [I]▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ and the following general formula [II] ▲ There are mathematical formulas, chemical formulas, tables, etc. 1. A method for producing an inclusion composition in which a cyclohexanecarboxylic acid derivative is included in the metacyclophane, the method comprising bringing the metacyclophane into contact with a cyclohexanecarboxylic acid derivative.