JPS61254564A - Purification of isoquinoline - Google Patents

Abstract

PURPOSE:To obtain the titled compound in high efficiency, by reacting a tar-based isoquinoline containing S compound as impurity with an acid to obtain a crystallizable salt, purifying the salt to a specific desulfurization degree e.g. by recrystallization and subjecting to the alkali decomposition to effect the desulfurization. CONSTITUTION:Tar base obtained from coal tar or liquefied coal oil, etc., by acid extraction process is fractioned to obtain a tar-based isoquinoline having a purity of >=90wt%. A neutral hydrocarbon solvent or a water-soluble organic solvent is added to the isoquinoline, the produced crystallizable salt is slurried and made to react with an aqueous solution of an acid, and after the completion of the reaction, water is separated and are moved from the system to precipitate the crystallizable salt of isoquinoline. The salt is purified by recrystallization and/or washing with an alcohol or its solution to attain a desulfurization degree of >=90% and then desulfurized by alkali decomposition to obtain purified isoquinoline. EFFECT:The S compounds which cannot be separated by distillation are removed at a highest degree. USE:Synthetic raw material for pharmaceuticals and agricultural chemicals, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] This invention relates to a method for purifying isoquinoline containing sulfur compounds as impurities.

[Conventional technology]

Isoquinoline, which has recently attracted attention as a synthetic raw material for medicines, agricultural chemicals, etc., can be synthesized by synthetic methods such as condensation of benzaldehyde and aminoacetal, and distillation of homophthalic acid imide with zinc dust. All of these synthetic methods involve complicated synthesis steps and high manufacturing costs, and are not practical for applications that require a large amount of isoquinoline as a raw material.

Isoquinoline can also be obtained at low cost by precision distillation of a tar base obtained by acid extraction from coal tar or coal liquefied oil, but in general, quinoline, quinaldine, 8 - Contains impurities such as methylquinoline and alkylpyridine, resulting in low purity, and such tar-based isoquinoline also contains sulfur compounds.

Therefore, in the past, several methods have been proposed to increase the purity of this tar-based isoquinoline. For example, in US Pat. No. 2,391,270, tar base is reacted with calcium chloride to obtain tar A method is shown for producing highly pure isoquinoline by producing a calcium chloride adduct of a base and decomposing it with water.

(Problems to be Solved by the Invention) The present invention efficiently purifies tar-based isoquinoline,
In particular, the object is to obtain tar-based isoquinoline from which sulfur compounds have been sufficiently removed.

Means and Actions for Solving Problem C The present invention was devised in view of this point of view, and it is possible to remove sulfur compounds that exist as impurities in tar-based isoquinoline and cannot be separated and removed by distillation. This method provides a method for separating and removing tar-based isoquinoline separated from coal tar or coal liquefied oil, etc. with an acid to prepare a crystalline salt, and this crystalline salt has a desulfurization rate of 90%. This is a method for purifying tar-based isoquinoline in which recrystallization and/or washing is performed as described above, followed by alkaline decomposition to obtain desulfurized ink quinoline.

In the present invention, the tar-based isoquinoline used as a raw material is mainly a distillate with a boiling point in the range of 242 to 245°C obtained by precision distillation of a tar base obtained by acid extraction from coal tar or tar-based oil such as coal liquefied oil. There is an isoquinoline fraction with a purity of 9, preferably 9 in terms of the desulfurization rate of isoquinoline and the recovery rate of desulfurized isoquinoline.
It is purified to a purity of 0% by weight or more, more preferably 95% or more. Such tar-based isoquinoline contains impurities such as quinoline, quinaldine, and 8-
In addition to basic substances such as methylquinoline and alkylpyridine, sulfur compounds having a sulfur atom in the compound usually contain about 0.1 to 1% of the total sulfur content.

The tar-based isoquinoline is converted into a crystalline salt by an acid that reacts with the isoquinoline to form a crystalline salt.

Examples of acids for preparing the crystalline salt of isoquinoline include mineral acids such as hydrochloric acid, nitric acid, perchloric acid, hydrobromic acid, sulfuric acid, and phosphoric acid, and organic acids such as oxalic acid and 0-7 talic acid. Among them, sulfuric acid, hydrochloric acid, and hydrobromic acid are preferred. The amount of acid used in preparing the crystalline salt of isoquinoline may be at least 1 mole, preferably 1.0 to 1.1 times the mole of isoquinoline.

There are no particular restrictions on the method for preparing crystalline salts by reacting these acids with tar-based isoquinoline, and conventionally known methods can be employed, but preferably neutral A method is to add a hydrocarbon solvent or a water-soluble organic solvent to form a slurry of the generated crystalline salt, or a method is to react using an acid aqueous solution and then remove water to precipitate the crystalline salt. Neutral hydrocarbon solvents used for this purpose include hexane, benzene, etc.; water-soluble organic solvents include alcohol, acetone, acetonitrile, etc.; and crystalline salts are prepared by reacting with aqueous acid solutions. In this case, alcohol may be used as a solvent, and water may be azeotropically removed with the alcohol after the reaction is completed.

The crystalline salt of isoquinoline thus prepared is
Next, it is purified by recrystallization and/or washing to achieve a desulfurization rate of 90% or more.

The solvent used for recrystallization and/or washing is one that can dissolve the crystalline salt of isoquinoline, and is preferably alcohol such as methanol, ethanol, n-propanol, isopropanol, or an aqueous alcohol solution. This recrystallization and/or washing method may include recrystallization only once or multiple times, washing only once or multiple times, or a combination of recrystallization and washing using conventionally known methods. can.

Although this recrystallization and/or washing varies depending on the amount of sulfur compounds contained in the tar-based isoquinoline used as a raw material, the desulfurization rate is 90% or more, preferably 95%.
It is necessary to reduce the sulfur content in the desulfurized isoquinoline to 3001) I) or less, preferably 100 ppm or less, more preferably 1 oppm or less.

This desulfurization rate is calculated by analyzing the desulfurized isoquinoline obtained by alkaline decomposition in the next step using an appropriate means, such as a gas chromatograph. 2-b) It is preferable to use pyridine.

The crystalline salt of isoquinoline thus obtained is then decomposed with an alkali to become desulfurized isoquinoline. As the alkali used in this alkaline decomposition, conventionally known alkalis such as a caustic soda aqueous solution, a caustic potash aqueous solution, and ammonia water can be used.

Desulfurized isoquinoline obtained by alkaline decomposition of a crystalline salt of isoquinoline can be used as a raw material for synthesis as it is, but it is preferably once distilled to obtain purified isoquinoline.

〔Example〕

The method of the present invention will be explained below based on Examples.

Example 1 Tar-based isoquinoline (purity 95%, total sulfur content 3, oo
100 parts of oppm) was dissolved in the reaction solvent shown in Table 1, and the acid shown in Table 1 (amount used in a molar ratio of isoquinoline to isoquinoline of 1:1) was added dropwise to the resulting solution at room temperature to react. ,
The slurry-formed reaction mixture was filtered to obtain a solid content, which was washed with a small amount of reaction solvent and dried to obtain a crystalline salt of isoquinoline.

Next, the above crystalline salt of isoquinoline was recrystallized with the recrystallization solvent shown in Table 1, and after drying, it was dissolved in the same amount of water as the crystalline salt and alkaline decomposed with a 20-30% aqueous solution of caustic soda to liberate it. The purified isoquinoline was fractionated, washed with water, dehydrated, and analyzed by gas chromatography. The purity, total sulfur content, and recovery rate of the purified isoquinoline obtained were determined according to U.S. Patent No. 2,
They are shown in Table 1 together with a comparative example purified by the method described in No. 391,270.

Example 2 100 parts by weight of the same tar-based isoquinoline as in Example 1 was dissolved in 40 C1 parts of benzene, 125 parts by weight of 48% hydrobromic acid was added dropwise to this solution at room temperature, and after the reaction was completed, benzene and water were distilled off. The solid content was obtained. This solid content was washed with a reaction solvent, dried, recrystallized with 125 parts by weight of 2-propatool, and subjected to alkaline decomposition in the same manner as in Example 1 above to obtain purified isoquinoline. The purity of this purified isoquinoline was about 100%, the total sulfur content was 7 DI)l, and the recovery rate of isoquinoline was 86%.

11.1 Example 3 Example 2 except that no reaction solvent was used and washing with n-propertool was performed instead of recrystallization.
Purified isoquinoline was obtained in the same manner as above. The purity of this purified isoquinoline is approximately 100%, and the total sulfur content is 18 pp.
m, and the recovery rate of isoquinoline was 88%.

Example 4 100 parts by weight of the tar-based isoquinoline used in Example 1 and 120 parts by weight of 47% hydrobromic acid were reacted with stirring under cooling, and after the reaction was completed, water was distilled off and washed with acetone for 2 hours.
This was repeated twice to obtain 144 parts by weight of isoquinoline hydrobromide.

i, ioo parts by weight of this isoquinoline hydrobromide
- 124 parts of purified isoquinoline hydrobromide with a total sulfur content of 22 ppm (recovery rate 85.
9%).

The above purified ink quinoline hydrobromide was recrystallized again with 1°000 parts by weight of 2-propanol, and dissolved in the same amount of water as the obtained repurified isoquinoline hydrobromide (113 parts by weight). , 82.5 parts by weight of desulfurized isoquinoline released by alkaline decomposition with a 20% aqueous sodium hydroxide solution was distilled to obtain 62.5 parts by weight of purified isoquinoline. The purity of this purified isoquinoline is 99.7%, and the total sulfur content is IEIE
Im or less, and the recovery rate of isoquinoline was 62.
It was 5%.

Example 5 100 parts by weight of the tar-based isoquinoline used in Example 1 was added to 360 parts by weight for No. 091, and 690 parts by weight for No. 2.
N061, respectively, dissolved in 1 part of n-propertool.
Then, 126 parts by weight of 47% hydrobromic acid was added dropwise to react, and then the reaction mixture was azeotropically distilled under the conditions shown in Table 2, and the azeotropic distillation residue was cooled to the temperature shown in Table 2 to form crystals. was precipitated, and the crystals obtained were alkali decomposed using a 20% caustic soda aqueous solution under the conditions shown in Table 2 to obtain purified isoquinoline. The purity, total sulfur content, and recovery rate of the purified inquinoline obtained are shown in Table 2.

Example 6 Tar-based isoquinoline (purity 96.1%, total sulfur content 3,
300111) Im) 100 parts by weight of methanol 60
81 parts of 97% concentrated sulfuric acid (1.1 times the mole of isoquinoline) was added dropwise to this solution with stirring under cooling, and the resulting reaction mixture was dissolved in 1.500 parts of 97% concentrated sulfuric acid.
rpm, to obtain isoquinoline sulfate by solid-liquid separation in a centrifuge, and after recrystallizing this isoquinoline sulfate with 400 parts by weight of methanol, it was dissolved in water and 95% aqueous sodium hydroxide solution. After adding 48 parts of benzene for alkaline decomposition, the isoquinoline liberated was extracted with 21 parts of benzene, the benzene extract of this isoquinoline was washed with water, and the benzene was distilled off to obtain purified isoquinoline. The purity of the purified isoquinoline obtained was 99.5%.
The total sulfur content was 50 DI)11, and the recovery rate was 52.9%.

Example 7 Tar-based isoquinoline (purity 95.5%, total sulfur content 4,
8001) pll) was dissolved in 560 parts by weight of isopropyl alcohol, and 75 parts by weight of 96% sulfuric acid was added dropwise to this solution while stirring while cooling. After the dropwise addition was completed, stirring was continued for another 30 minutes, and then slowly cooled. The precipitated isoquinoline sulfate was filtered off to obtain 208 parts of wet crystals (recovery rate: 89.3% by weight).

100 parts by weight of this wet crystal was mixed with 40 parts by weight of isopropyl alcohol.
Recrystallized with a mixed solvent of 0 parts by weight and 55 parts by weight of earth and water to obtain 63.5 parts by weight of isoquinoline sulfate (recovery rate 84.1% by weight).
I got it. The total sulfur content in the isoquinoline obtained by partially alkaline decomposition of this crystal was 362 E)Elm.

60 parts by weight of the crystals were recrystallized for the second time in a mixed solvent of 240 parts by weight of isopropyl alcohol and 32 parts by weight of earth water to obtain 51 parts by weight of isoquinoline sulfate. The recovery rate of the second recrystallization was 85.1% by weight, and the purified isoquinoline obtained by alkaline decomposition had a total sulfur content of 4.
81)I)l, and the total recovery rate was 63.9% by weight.

〔Effect of the invention〕

According to the method of the present invention, sulfur compounds that exist as impurities in tar-based isoquinoline and cannot be separated and removed by distillation can be separated and removed as much as possible, and at the same time, the purity of the isoquinoline can be improved.

Patent applicant Nippon Steel Chemical Co., Ltd. Agent
Patent attorney Katsuo Naruse (2 others)

Claims (5)

[Claims] (1) A crystalline salt is prepared by reacting tar-based isoquinoline separated from coal tar or coal liquefied oil with an acid, and this crystalline salt is recrystallized and/or washed to achieve a desulfurization rate of 90% or more. , followed by alkaline decomposition to obtain desulfurized isoquinoline. (2) The tar-based isoquinoline is purified to a purity of 90% by weight or more by distilling a tar base obtained by acid extraction from coal tar or coal liquefied oil, etc. Purification of the isoquinoline according to claim 1 Law. (3) In reacting tar-based isoquinoline with acid, a neutral hydrocarbon solvent or a water-soluble organic solvent is added, and the resulting crystalline salt is slurried. Claim 1
The method for purifying isoquinoline described in . (4) The method for purifying isoquinoline according to claim 1, wherein an aqueous acid solution is used as the acid, and after the reaction is completed, water is separated and removed to precipitate a crystalline salt of isoquinoline. (5) The method for purifying isoquinoline according to claim 1, wherein the recrystallization and/or washing solvent is alcohol or an aqueous alcohol solution.