A method for ionic liquid catalysis of racemic dextran base
By using ionic liquid catalysts to assist microwave racemization reactions and combining them with extraction and distillation steps, the problem of catalyst degradation and recovery difficulties in the racemization process of dextroimidazole base was solved, achieving a highly efficient and environmentally friendly racemization process and reducing production costs.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- JIANGSU TIANHE PHARMA CO LTD
- Filing Date
- 2023-11-30
- Publication Date
- 2026-05-26
AI Technical Summary
Existing technologies for the racemic process of dextroimidazole base suffer from problems such as catalyst degradation and recovery difficulties, environmental pollution, and high cost and difficulty in recycling of traditional catalysts.
Using ionic liquids as green catalysts, and through microwave-assisted racemic reactions combined with extraction and distillation steps, highly efficient racemization of dextroimidazole base is achieved. The ionic liquids are easy to separate and recover for reuse.
It improves the efficiency of racemic reactions and product yield, reduces production costs and environmental pollution, and achieves catalyst stability and recyclability.
Abstract
Description
Technical Field
[0001] This invention relates to the field of chemical preparation technology, and in particular to a method for catalyzing the racemization of dextroimidazole base using ionic liquids. Background Technology
[0002] Levamisole hydrochloride is an anthelmintic and biological response modifier. It is effective against ascariasis, hookworm infection, pinworm infection, and strongyloidiasis. Due to its high single-dose efficacy, it is suitable for group treatment.
[0003] Tetraimidazole hydrochloride is chirally resolved to prepare levamisole hydrochloride, with dextroimidazole base as a byproduct. Dextroimidazole base can be racemic to prepare tetraimidazole hydrochloride, thereby achieving full utilization of materials and reducing environmental pressure.
[0004] There are two main racemization mechanisms for dextroimidazole bases. One involves racemization at high temperatures using dimethyl sulfoxide (DMSO) as a solvent and strong inorganic bases (such as potassium hydroxide and sodium hydroxide) as catalysts. Under these conditions, both dextroimidazole base and DMSO undergo partial degradation; simultaneously, DMSO cannot be effectively recovered, increasing costs and environmental pollution.
[0005] Secondly, foreign literature reports the use of crown ethers (14-alkyl-4) as catalysts for racemization, achieving yields exceeding 90%. Most crown ethers are readily soluble in water and toxic; this process results in expensive crown ethers that are difficult to recover, causing environmental pollution. Summary of the Invention
[0006] The purpose of this invention is to address the shortcomings of existing technologies by providing a method for catalyzing the racemization of dextroimidazole bases using ionic liquids. This method employs a green catalyst that is low in toxicity and exhibits high activity in the racemization of dextroimidazole bases.
[0007] To achieve the above-mentioned objectives, the method for catalyzing the racemization of dextroimidazole base using ionic liquids of the present invention employs the following technical solution:
[0008] A method for catalyzing the racemization of dextroimidazole base using an ionic liquid, wherein dextroimidazole base undergoes a racemic reaction catalyzed by an ionic liquid, and is then extracted to obtain tetraimidazole base; wherein the ionic liquid is a basic quaternary ammonium salt ionic liquid.
[0009] Preferably, it includes the following steps:
[0010] (1) Dextroimidazole base and ionic liquid undergo a racemic reaction under microwave irradiation to obtain a racemic reaction solution;
[0011] (2) The racemic reaction solution was extracted with water and dichloromethane, and the organic phase was dried and desoluble in dichloromethane to obtain tetraimidazole base;
[0012] (3) Aqueous phase is distilled under reduced pressure, and the residue is an ionic liquid, which can be reused after activation.
[0013] Preferably, the ionic liquid is one or both of diethylenetriamine acetate and triethylenetetramine acetate.
[0014] Preferably, the ratio of the dextroimidazole base to the ionic liquid is 1:1 to 5.
[0015] Preferably, the ratio of the dextroimidazole base to the ionic liquid is 1:2 to 3.
[0016] Preferably, the temperature of the racemic reaction in step (1) is 30 to 60°C.
[0017] Preferably, the temperature of the racemic reaction in step (1) is 40-50°C.
[0018] Preferably, the racemic reaction time in step (1) is 30 to 120 minutes.
[0019] Preferably, the racemic reaction time in step (1) is 50 to 60 minutes.
[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0021] 1. This invention uses ionic liquid as a novel green catalyst, which has advantages such as stability, low toxicity, designable structure, high efficiency, and environmental friendliness. It has high activity in racemic dextrorotatory bases and is easy to separate and recycle.
[0022] 2. This invention reduces the use of organic solvents, which can lower the production cost and environmental pollution of the product, increase the product yield, and provide greater feasibility for commercial production. Detailed Implementation
[0023] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. After reading the present invention, any modifications of the present invention in various equivalent forms by those skilled in the art will fall within the scope defined by the appended claims.
[0024] Example 1
[0025] 100g of dextroimidazole base and 300g of diethylenetriamine acetate were added to a reaction flask. The microwave reactor was turned on, and the power was set to 500W, the temperature to 45℃, and the time to 50 minutes. After the reaction was completed, the temperature was lowered to below 30℃, and 200ml of dichloromethane and 200ml of water were added and stirred for 30 minutes. The mixture was then separated. 200ml of dichloromethane was added to the aqueous phase, and the mixture was stirred for 30 minutes and then separated. The organic phases were combined, washed twice with 200ml of water, and dried over anhydrous sodium sulfate. Dichloromethane was recovered under normal pressure, and the mixture was evaporated under reduced pressure to obtain 98.4g of tetraimidazole base, with a yield of 98.4%. Specific rotation (EP standard): 0.22°.
[0026] After merging the aqueous phases, the mixture is distilled under reduced pressure. The residue is then treated and the resulting ionic liquid can be recycled.
[0027] Example 2
[0028] 100g of dextroimidazole base and 200g of triethylenetetramine acetic acid were added to a reaction flask. The microwave reactor was turned on, and the power was set to 500W, the temperature to 55℃, and the time to 80 minutes. After the reaction was completed, 200ml of dichloromethane and 200ml of water were added and stirred for 30 minutes, followed by separation. 200ml of dichloromethane was added to the aqueous phase and stirred for 30 minutes, followed by separation. The organic phases were combined, washed twice with 200ml of water, and dried over anhydrous sodium sulfate. Dichloromethane was recovered under normal pressure, and the solution was evaporated under reduced pressure to obtain 99.1g of tetraimidazole base, with a yield of 99.1%. Specific rotation (EP standard): 0.37°.
[0029] After merging the aqueous phases, the mixture is distilled under reduced pressure. The residue is then treated and the resulting ionic liquid can be recycled.
[0030] Example 3
[0031] 100g of dextroimidazole base and 400g of triethylenetetramine acetic acid were added to a reaction flask. The microwave reactor was turned on, and the power was set to 500W, the temperature to 50℃, and the time to 40 minutes. After the reaction was completed, 200ml of dichloromethane and 200ml of water were added and stirred for 30 minutes, followed by separation. 200ml of dichloromethane was added to the aqueous phase and stirred for 30 minutes, followed by separation. The organic phases were combined, washed twice with 200ml of water, and dried over anhydrous sodium sulfate. Dichloromethane was recovered under normal pressure, and the solution was evaporated under reduced pressure to obtain 97.9g of tetraimidazole base, with a yield of 97.9%. Specific rotation (EP standard): 0.14°.
[0032] After merging the aqueous phases, the mixture is distilled under reduced pressure. The residue is then treated and the resulting ionic liquid can be recycled.
[0033] Example 4
[0034] 100g of dextroimidazole base and the recovered ionic liquid from Example 3 were added to a reaction flask. The microwave reactor was turned on, and the power was set to 500W, the temperature to 50℃, and the time to 40 minutes. After the reaction was completed, 200ml of dichloromethane and 200ml of water were added and stirred for 30 minutes, followed by separation. 200ml of dichloromethane was added to the aqueous phase and stirred for 30 minutes, followed by separation. The organic phases were combined, washed twice with 200ml of water, and dried with anhydrous sodium sulfate. Dichloromethane was recovered under normal pressure, and the solution was evaporated under reduced pressure to obtain 98.3g of tetraimidazole base, with a yield of 98.3%. Specific rotation (EP standard): 0.25°.
[0035] After merging the aqueous phases, the mixture is distilled under reduced pressure. The residue is then treated and the resulting ionic liquid can be recycled.
Claims
1. A method for catalyzing the racemization of dextroimidazole base using ionic liquids, characterized in that, Dextroimidazole base undergoes a racemic reaction catalyzed by an ionic liquid, followed by extraction to obtain tetraimidazole base; the ionic liquid is one or both of diethylenetriamine acetate and triethylenetetramine acetate.
2. The method for catalyzing the racemization of dextroimidazole base using ionic liquids according to claim 1, characterized in that, Includes the following steps: (1) Dextroimidazole base and ionic liquid undergo a racemic reaction under microwave irradiation to obtain a racemic reaction solution; (2) The racemic reaction solution was extracted with water and dichloromethane, and the organic phase was dried in dichloromethane to obtain tetraimidazole base; (3) Aqueous phase vacuum distillation, the residue is ionic liquid, which can be reused after activation.
3. The method for catalyzing the racemization of dextroimidazole base using ionic liquids according to claim 1, characterized in that: The ratio of dextromethorphan base to ionic liquid is 1:1~5.
4. The method for catalyzing the racemization of dextroimidazole base using an ionic liquid according to claim 3, characterized in that: The ratio of dextromethorphan base to ionic liquid is 1:2~3.
5. The method for catalyzing racemization of dextroimidazole base using ionic liquid according to claim 2, characterized in that: The temperature of the racemic reaction in step (1) is 30~60℃.
6. The method for catalyzing the racemization of dextroimidazole base using an ionic liquid according to claim 2, characterized in that: The temperature of the racemic reaction in step (1) is 40~50℃.
7. The method for catalyzing racemization of dextroimidazole base using ionic liquid according to claim 2, characterized in that: The racemic reaction in step (1) takes 30 to 120 minutes.
8. The method for catalyzing racemization of dextroimidazole base using ionic liquid according to claim 2, characterized in that: The racemic reaction in step (1) takes 50 to 60 minutes.