Preparation method of tetraimidazole hydrochloride

A technology of tetraimidazole hydrochloride and tetraimidazole, applied in the direction of organic chemistry and the like, can solve the problems of long reaction route, difficult reaction yield, low yield, etc., and achieve the effects of easy industrialization, good industrialization prospects and significant economic benefits.

Active Publication Date: 2021-02-12
SHANDONG GUOBANG PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The synthesis of existing tetramisole hydrochloride requires a long reaction process, which also makes it difficult to improve the reaction yield of this method. From styrene oxide to tetramisole hydrochloride, the total yield is about 70%.
[0007] Patent CN102603773A discloses the synthesis process of tetramisole, including chlorination reaction and neutralization ring closure reaction, the reaction route is relatively long, and the initial raw material used in this process is hydroxy salt 2-imino-α-phenyl-3-thiazolidineethanol Hydrochloride itself is obtained through complex chemical synthesis, the yield is not high (about 75% based on styrene oxide), the price is relatively expensive, and there are also problems of a large amount of waste water and waste salt in the preparation process of hydroxy salt
[0008] Although the patent CN111138457A has made further technical improvements in the step of preparing tetramisole hydrochloride from hydroxyl salts, it still does not change the conditions for using hydroxyl salts

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] (1) Feeding

[0038] Take 26.43g (0.1mol) of 1,2-dibromoethylbenzene and add it to 100mL of DMF solution to dissolve completely. Add 15.14g (0.11mol) of 2-aminothiazoline hydrochloride and 11.67g (0.11mol) of sodium carbonate particles for mixed reaction.

[0039] (2) The first stage reaction

[0040] In the first stage of the reaction, the temperature was raised to 85°C for 2 hours;

[0041] (3) The second stage reaction

[0042] Then in the second stage of the reaction, continue to add 5.84g (0.055mol) of sodium carbonate particles, raise the temperature to 160°C and reflux, and react for 16 hours until the conversion of the 1,2-dibromoethylbenzene raw material is complete.

[0043] (4) Post-processing

[0044] Cool the reaction system to room temperature, filter and discard the insoluble matter, distill the filtrate under reduced pressure, recover DMF, concentrate the solid to dryness (19.01g), mix 100mL dichloromethane and 100mL purified water for stirring and d...

Embodiment 2

[0046] (1) Feeding

[0047] Add 26.51g of 1,2-dibromoethylbenzene into 100mL of DMF solution. Add 13.81g of 2-aminothiazoline hydrochloride and 10.64g of sodium carbonate particles for mixed reaction.

[0048] (2) The first stage reaction

[0049] In the first stage of the reaction, the temperature was raised to 90° C., and the reaction was performed for 2 hours.

[0050] (3) The second stage reaction

[0051] Then in the second stage of the reaction, continue to add 5.32 g of sodium carbonate particles, raise the temperature to reflux, and react for 15 hours until the conversion of the 1,2-dibromoethylbenzene raw material is complete.

[0052] (4) Post-processing

[0053]Subsequent treatment was the same as in Example 1, followed by filtration and drying to obtain 20.53 g of white powder, namely tetramisole hydrochloride product, with a detection purity of 99.03% and a calculated yield of 84.17%.

Embodiment 3

[0055] (1) Feeding

[0056] Add 26.47g of 1,2-dibromoethylbenzene into 100mL of DMF solution. Add 16.54g of 2-aminothiazoline hydrochloride and 12.75g of sodium carbonate granules for mixed reaction.

[0057] (2) The first stage reaction

[0058] In the first stage of the reaction, the temperature was raised to 80°C for 2 hours.

[0059] (3) The second stage reaction

[0060] Then in the second stage of the reaction, continue to add 6.38g of sodium carbonate particles, raise the temperature to reflux, and react for 14 hours until the conversion of the 1,2-dibromoethylbenzene raw material is complete.

[0061] (4) Post-processing

[0062] Subsequent treatment was the same as in Example 1, followed by filtration and drying to obtain 20.88 g of white powder, namely tetramisole hydrochloride product, with a detection purity of 99.15% and a calculated yield of 86.58%.

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PUM

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Abstract

The invention provides a preparation method of tetraimidazole hydrochloride, which comprises the following steps: preparing tetraimidazole; the preparation method comprises the following step: reacting tetraimidazole, 1, 2-dibromoethyl benzene and 2-aminothiazoline hydrochloride to generate tetraimidazole. The synthetic route is shorter, the comprehensive yield is higher than that of other processroutes, styrene is used as an initiator, tetra-imidazole free alkali is used as a final product, the yield of the hydroxysalt process route is about 65%, the yield of the N (2chloroethyl) alpha (chloromethyl) benzylamine hydrochloride process route is about 72%, and the yield can reach 85% or above when the patent route is used. Meanwhile, the problem of large amount of waste water and waste saltgenerated by multi-step reactions such as chlorination, hydrolysis and cyclization is avoided, the investment of reaction equipment such as an autoclave is avoided, the green chemical engineering requirement is met, the economic benefit is remarkable, and the industrial prospect is good.

Description

technical field [0001] The invention belongs to the technical field of organic chemical production, in particular to a preparation method of tetramisole hydrochloride. Background technique [0002] Levamisole, CAS number: 14769-73-4, molecular formula: C 11 h 12 N 2 S, white to off-white crystalline powder. DL-tetramisole is separated and neutralized with caustic soda to obtain L-tetramisole, which is finally salted. Levamisole (levamisole) is a broad-spectrum anthelmintic drug, which can inhibit the activity of succinate dehydrogenase in the muscle of parasites, causing continuous muscle contraction and paralysis. and resistance to viral infection. At present, it is used as an adjuvant therapy for lung cancer, breast cancer surgery, acute leukemia, and advanced lymphoma after chemotherapy. In addition, it can still be used for autoimmune diseases such as rheumatoid arthritis, lupus erythematosus and influenza, children with respiratory tract infections, hepatitis, bac...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D513/04
CPCC07D513/04
Inventor 李琦斌乔建超杨志豪程贺王召平
Owner SHANDONG GUOBANG PHARMA
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