JPH06287149A - Separation of distributed benzene isomer and agent for separation process - Google Patents

Abstract

PURPOSE:To separate a mixture of disubstituted benzene derivatives into constituent components with simple liquid-liquid extraction in high selectivity by using a substituted cyclodextrin as a clathrate-separation agent. CONSTITUTION:A disubstituted benzene derivative mixture is made to contact with a substituted cyclodextrin produced by substituting the hydrogen atom of at least one hydroxyl group of a cyclodextrin with at least one group selected from glucosyl, maltosyl, maltooligosaccharide residue, methyl, hydroxyethyl, hydroxypropyl, sulfonic acid group, alkylenesulfonic acid group and carboxyalkyl (preferably under stirring or shaking at 20-25 deg.C) to form disubstituted benzene derivative clathrate complex of the substituted cyclodextrin according to the clathrate complex forming constant of each isomer and the disubstituted benzene derivative is separated from the clathrate complex. Since the substituted cyclodextrin molecule is not decomposed, it can be recovered and reused. The process is applicable for the separation of mixture containing any combination of three kinds of disubstituted benzene derivatives.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an effective method for separating benzene di-substituted isomers, which is useful as a raw material for chemical synthesis and as a solvent, and a drug for inclusion and separation of the benzene di-substituted isomers. Specifically, the substituted cyclodextrin is used as a separating agent by utilizing the function of selectively encapsulating a benzene di-substituted isomer according to its size and shape, and contacting this with a benzene di-substituted isomer mixture, The present invention relates to a method for desorbing and collecting a benzene di-substituted isomer selectively concentrated from a generated inclusion complex, and a drug for separating the benzene di-substituted isomer.

[0002]

2. Description of the Related Art As a method for separating benzene di-substituted isomers, a distillation method utilizing a difference in boiling point or a crystallization method utilizing a difference in melting point is generally used. In the distillation method, since the boiling points of the isomers of the disubstituted benzene compound are relatively close to each other, precision distillation has to be repeated, but this not only takes time, but also consumes a large amount of energy. Also,
In the crystallization method, the position of the composition of the eutectic point is a problem, and effective separation cannot be performed unless the composition of the raw material used for crystallization is as far as possible from the eutectic point.

Separation of benzene di-substituted isomers is also carried out by gas chromatography or high performance liquid chromatography, but these are mainly used for analysis and are not suitable for industrial handling in large quantities. As a technique related to the present invention, a patent has already been applied for the separation of benzene compound isomers using cyclodextrin or chemically modified cyclodextrin as a separating agent (for example, JP-A-52-42825, "Benzene"). In the compound isomer separation method "), the inclusion complex is in a precipitation form and solid-liquid separation operation is necessary.

However, since the solid of the cyclodextrin inclusion complex is extremely fine and the solid-liquid separation operation is very troublesome, this is the greatest difficulty in carrying out the separation method.

[0005]

DISCLOSURE OF THE INVENTION The present invention utilizes a substituted cyclodextrin produced for the purpose of improving solubility, and is a novel and economical method for separating benzene disubstituted isomers with high selectivity. And an agent for separating the benzene di-substituted isomer.

[0006]

According to the present invention, a mixture of benzene di-substituted isomers (o-, m- and p-forms) and hydrogen of at least one hydroxyl group of cyclodextrin are
Glucosyl group, maltosyl group, maltooligosaccharide residue, methyl group, hydroxyethyl group, hydroxypropyl group,
A benzene di-substituted isomer inclusion complex of the substituted cyclodextrin is obtained by bringing the substituted cyclodextrin substituted with at least one of a sulfonic acid group, an alkylene sulfonic acid group and a carboxyalkyl group into contact with each other. Formed according to the inclusion complex formation constant,
Next, a method for separating a benzene di-substituted isomer from the inclusion complex, the method comprising separating the benzene di-substituted isomer, and hydrogen of at least one hydroxyl group of cyclodextrin is a glucosyl group, maltosyl group, maltooligosaccharide residue Agent for inclusion and separation of benzene di-substituted isomers, which comprises a substituted cyclodextrin substituted with at least one of the following: a methyl group, a hydroxyethyl group, a hydroxypropyl group, a sulfonic acid group, an alkylenesulfonic acid group and a carboxyalkyl group Will be provided.

The present invention will be described in detail below. In the present invention, hydrogen of at least one hydroxyl group of cyclodextrin is used as a drug for separating benzene di-substituted isomers, and glucosyl group, maltosyl group, maltooligosaccharide residue, methyl group,
A substituted cyclodextrin substituted with at least one of a hydroxyethyl group, a hydroxypropyl group, a sulfonic acid group, an alkylenesulfonic acid group and a carboxyalkyl group is used. Here, the cyclodextrin may be any of α-, β- and γ-cyclodextrin.

Since these substituted cyclodextrins have a higher solubility in water of the inclusion complex of the disubstituted benzene isomer itself and water than other cyclodextrins or substituted ones, it is not necessary to make them into a slurry state, for example. Can also be treated as a high-concentration aqueous solution. Further, since the inclusion complex does not precipitate during the formation of the inclusion complex and the solid-liquid separation operation is unnecessary,
There is a significant advantage that the whole process is simple.

The inclusion cyclodextrin used in the present invention, especially the inclusion with glucosyl-cyclodextrin or maltosyl-cyclodextrin, has already been applied to the food field and the like. There is no example in which the inclusion complex-forming ability of these substituted cyclodextrins is used for the purpose of separating the.

In the present invention, these substituted cyclodextrins are dissolved in water and a mixture of benzene disubstituted isomers such as xylene, dichlorobenzene,
Chlorotoluene, chloronitrobenzene, nitrotoluene, dinitrobenzene, bromotoluene, chlorobenzotrifluoride, aminothiophenol, divinylbenzene, vinyltoluene, aminobenzotrifluoride, bis (trifluoromethyl) benzene, chlorobenzyl chloride, fluorobenzyl chloride, Add an isomer mixture of bromonitrobenzene, fluoronitrobenzene, fluorotoluene, fluoroaniline, fluorobenzonitrile, etc. and vigorously stir or shake. However, the present inventors have already filed a patent application for a method for separating xylene isomers using a substituted α-cyclodextrin (Japanese Patent Application No. 2-121212), and the present invention excludes this. The concentration of the substituted cyclodextrin is 5 to 100% by weight with respect to water, preferably 10 to 30% by weight. In addition, in the case of other substituted cyclodextrins such that the solubility of the cyclodextrin having no substituent or the benzene di-substituted isomer inclusion complex in water is less than 5% by weight, the inclusion complex is formed in the process. The inclusion complex precipitates are generated, and the operation at a remarkably low concentration is forced to be inconvenient, but the specific substituted cyclodextrin used in the present invention does not cause such inconvenience.

The mixing ratio of the substituted cyclodextrin solution and the benzene disubstituted isomer mixture is such that the number of moles of the benzene disubstituted isomer is 1 to 1 of that of the substituted cyclodextrin.
Make it 0 times. Stir or shake as vigorously as possible for a few seconds to tens of minutes. The temperature is 10
The temperature is 40 ° C., preferably 20 to 25 ° C. After completion of stirring or shaking, oil-water separation is performed by an appropriate method. Eg 5
A known means used for improving the separability between the oil layer and the aqueous layer in liquid-liquid extraction such as centrifugation for 10 minutes or addition of a salt can be used.

In order to obtain the benzene disubstituted isomer from the inclusion complex dissolved in the water layer, the cyclodextrin inclusion complex is dissociated in an aqueous solution at 60 to 70 ° C. or higher based on the known fact. Is heated to 60 ° C. or higher to dissociate the included benzene di-substituted isomer,
Use a volatile organic solvent having a relatively low boiling point, such as ethyl ether or n-hexane, which is hard to be separated from the aqueous layer or included in the substituted cyclodextrin and is hardly dissolved in water, at room temperature or 60- The benzene di-substituted isomer is extracted into the organic layer under heating at 70 ° C. At this time, the aqueous layer becomes a transparent substitution type cyclodextrin aqueous solution. Moreover, the benzene di-substituted isomer is obtained by evaporating the organic solvent from the organic layer from which the benzene di-substituted isomer is extracted.

When separation of the benzene di-substituted isomer is insufficient in one inclusion, and other components are also mixed, the inclusion-separated benzene di-substituted isomer mixture is used as a starting material for repeated substitution-type cyclohexane. By performing inclusion with dextrin, the purity of the target disubstituted benzene isomer can be increased.

It should be noted that the substituted cyclodextrin molecule used in the present invention itself is not decomposed in the above-mentioned whole process, so that it can be recovered and reused.

In the present invention, three types of substituted cyclodextrins (o-, m-, p-) are used as agents for inclusion and separation.
It is applicable to separation of a mixture containing all combinations of benzene di-substituted isomers.

[0016]

The present invention will be described in more detail with reference to the following examples. Example 1 0.729 g of monomaltosyl-β-cyclodextrin
Was dissolved in 5 g of water, and 0.735 g of a mixture containing 65% and 35% of o- and p-dichlorobenzene was added.

After stirring at 25 ° C. for 5 minutes, the reaction product was centrifuged at 3,000 rpm for 5 minutes, the aqueous layer was taken out, and this was shaken with ethyl ether, and ether was volatilized from the ether layer to form an organic layer. The compound was obtained.

Table 1 shows the composition changes of the components in this example. This was analyzed by capillary gas chromatography, and the numbers in the table indicate the weight percentage of each component.

[0019]

Example 2 The contents of o- and p-dichlorobenzene were 84% respectively.
% And 16% were performed in the same manner as in Example 1. The results are shown in Table 2.

[0021]

Example 3 The contents of o- and p-dichlorobenzene were 93% respectively.
% And 7%, but the same operation as in Example 1. The results are shown in Table 3.

[0023]

Example 4 Example 1 was repeated except that 0.656 g of methyl-β-cyclodextrin was used instead of monomaltosyl-β-cyclodextrin. The results are shown in Table 4.

[0025]

Example 5 0.722 g of hydroxyethyl-β-cyclodextrin instead of monomaltosyl-β-cyclodextrin
The same procedure as in Example 1 was performed except that was used. The results are shown in Table 5.

[0027]

Example 6 Example 6 was carried out in the same manner as in Example 1 except that the dichlorobenzene isomer mixture was contained in the o-, m- and p-forms in equal amounts. The results are shown in Table 6.

[0029]

Example 7 1.34 g of monoglucosyl-β-cyclodextrin was dissolved in 10 g of water, and 3 g of commercial grade xylene was added.
Thereafter, the same procedure as in Example 1 was performed. Table 7 shows the composition changes of the ingredients
Shown in.

[0031]

Example 8 Instead of commercial grade xylene, ethylbenzene and o-,
The procedure of Example 7 was repeated except that 3 g of an equal mixture of m- and p-xylene isomers was used. The results are shown in Table 8.

[0033]

Example 9 Example 7 was repeated except that 3 g of an equal mixture of m- and p-xylene isomers was used in place of the commercially available special grade xylene. The results are shown in Table 9.

[0035]

Example 10 0.729 g of monomaltosyl-β-cyclodextrin
Was dissolved in 5 g of water, and 0.686 g of a mixture containing 63%, 4%, and 33% of o-, m-, and p-nitrotoluene, respectively.
Was added. Thereafter, the same procedure as in Example 1 was performed. The results are shown in Table 1.
It shows in 0.

[0037]

Example 11 0.729 g of monomaltosyl-β-cyclodextrin
Is dissolved in 5 g of water, and a mixture containing o-, m-, p-chlorobenzotrifluoride (CBTF) in equal amounts 0.9.
05g was added. Thereafter, the same procedure as in Example 1 was performed. The results are shown in Table 11.

[0039]

Example 12 0.729 g of monomaltosyl-β-cyclodextrin
Is dissolved in 5 g of water, and 0.906 g of a mixture containing o- and p-chlorobenzotrifluoride (CBTF) in equal amounts.
Was added. Thereafter, the same procedure as in Example 1 was performed. The results are shown in Table 1.
2 shows.

[0041]

Example 13 0.729 g of monomaltosyl-β-cyclodextrin
Was dissolved in 5 g of water, and 0.633 g of a mixture containing equal amounts of o- and p-chlorotoluene was added. Thereafter, the same procedure as in Example 1 was performed. The results are shown in Table 13.

[0043]

Example 14 0.584 g of monoglucosyl-α-cyclodextrin
Was dissolved in 5 g of water, and 0.70 g of an equal mixture of o-, m- and p-nitrotoluene isomers was added. Hereinafter, Example 1
I went the same way. The results are shown in Table 14.

[0045]

Example 15 0.568 g of monoglucosyl-α-cyclodextrin
Was dissolved in 5 g of water, and 0.74 g of a mixture containing 65% and 35% of o- and p-dichlorobenzene was added. Thereafter, the same procedure as in Example 1 was performed. The results are shown in Table 15.

[0047]

[0048]

EFFECTS OF THE INVENTION According to the present invention, each component can be highly selectively separated from a benzene disubstituted isomer mixture by a simple operation of liquid-liquid extraction. In addition, since the substituted cyclodextrin used for extraction can be used again for extraction,
The benzene disubstituted isomer can be separated at low cost.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Reference number within the agency FI Technical display location C07C 201/16 7188-4H 205/06 7188-4H (72) Inventor Hideki Takahashi Tsurumi, Yokohama-shi, Kanagawa 13-46, Daikokucho, Tokyo

Claims (2)

[Claims] 1. A mixture of benzene di-substituted isomers (o-, m-, and p-forms) and hydrogen of at least one hydroxyl group of cyclodextrin is a glucosyl group, a maltosyl group, a maltooligosaccharide residue, Substituted cyclodextrin benzene by contacting with a substituted cyclodextrin substituted with at least one of a methyl group, a hydroxyethyl group, a hydroxypropyl group, a sulfonic acid group, an alkylenesulfonic acid group and a carboxyalkyl group. A method for separating a benzene disubstituted isomer, which comprises forming a disubstituted isomer inclusion complex according to each inclusion complex formation constant and then desorbing the benzene disubstituted isomer from the inclusion complex. 2. The hydrogen of at least one hydroxyl group of cyclodextrin is a glucosyl group, maltosyl group, maltooligosaccharide residue, methyl group, hydroxyethyl group, hydroxypropyl group, sulfonic acid group, alkylene sulfonic acid group and carboxyalkyl group. An agent for inclusion and separation of benzene di-substituted isomers, which comprises a substituted cyclodextrin substituted with at least one of the above.