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Continuous production method suitable for ibuprofen Friedel-Crafts reaction

A technology of Friedel-Crafts reaction and production method, applied in the field of continuous production of Friedel-Crafts reaction of ibuprofen, can solve the problems of large fluctuation of product quality, many manual operation steps, low production efficiency and the like, and achieves shortening reaction residence time, The effect of ensuring product quality and reducing labor intensity

Active Publication Date: 2022-02-25
SHANDONG XINHUA PHARMA CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the traditional technology adopting the batch method, there are many manual operation steps, and the control of the reaction temperature is unstable, resulting in large fluctuations in the quality of each batch of products and low production efficiency. A production cycle takes about 5-8 hours; at the same time, in the traditional batch production method Reactor stirring cannot achieve rapid mixing, resulting in poor selectivity of isobutylbenzene reaction, and the content of the generated impurity ortho-chlorone is more than 3%, which affects product yield and quality; when the production load is large, by controlling the reaction kettle jacket The method of adjusting the reaction temperature by refrigerant cannot remove a large amount of reaction heat in a timely and effective manner, which may easily cause the reaction temperature to exceed the process requirements and affect product quality.

Method used

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  • Continuous production method suitable for ibuprofen Friedel-Crafts reaction

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Embodiment 1

[0024] The chloropropionyl chloride complex solution 9 prepared by chloropropionyl chloride, dichloromethane and aluminum chloride has a flow rate of 367.1kg / h, and is mixed uniformly with the Friedel-Crafts reaction circulating liquid in a static mixer 1 to obtain a mixed solution; Liquid and 111.2kg / h of isobutylbenzene 10 enter jet reactor 2 to react simultaneously, wherein mixed liquid is used as jet reactor 2 active flow, and isobutylbenzene 10 is used as jet reactor 2 driven flow; Jet reactor 2 and band The stirred Friedel-Crafts reactor 3 is connected to the top, and the material enters the Friedel-Crafts reactor 3 for further reaction, and the reaction temperature in the reactor is controlled at 5°C; the ketone solution is discharged through the circulation pump 4, wherein the feed liquid with a flow rate of 4000kg / h is circulated After the cooler 5 is cooled to -2°C, it enters the static mixer 1, and is mixed with the chloropropionyl chloride complex solution 9 as a ci...

Embodiment 2

[0026] This embodiment relates to the continuous production method of ibuprofen Friedel-Crafts reaction. The chloropropionyl chloride complex solution 9 prepared by chloropropionyl chloride, dichloromethane and aluminum chloride has a flow rate of 367.1kg / h, and is mixed uniformly with the Friedel-Crafts reaction circulating liquid in a static mixer 1 to obtain a mixed solution; Liquid and 111.2kg / h of isobutylbenzene 10 enter jet reactor 2 to react simultaneously, wherein mixed liquid is used as jet reactor 2 active flow, and isobutylbenzene 10 is used as jet reactor 2 driven flow; Jet reactor 2 and band The stirred Friedel-Crafts reactor 3 is connected to the top, and the material enters the Friedel-Crafts reactor 3 for further reaction, and the reaction temperature in the reactor is controlled at 10°C; the ketone solution is discharged through the circulating pump 4, and the feed liquid with a flow rate of 2000kg / h is circulated After the material cooler 5 is cooled to 0°C,...

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Abstract

The invention provides a continuous production method suitable for an ibuprofen Friedel-Crafts reaction, which is characterized in that a chloropropionyl chloride complexing solution and a Friedel-Crafts reaction circulating solution are uniformly mixed in a static mixer to obtain a mixed solution, the mixed solution and isobutylbenzene enter a jet reactor at the same time, the mixed solution is used as a jet reactor driving flow, and the isobutylbenzene is used as a jet reactor driven flow; a chloroketone solution generated by the Friedel-Crafts reaction is continuously discharged through a circulating pump; according to the invention, the continuous production of the ibuprofen Friedel-Crafts reaction is realized, the automatic control is easy to realize, the safety of the system is improved, the labor intensity is reduced, the reaction retention time is shortened, and the production efficiency is improved by more than 5-10 times.

Description

technical field [0001] The invention relates to the field of chemical pharmacy, more specifically, to a continuous production method of ibuprofen Friedel-Crafts reaction. Background technique [0002] Ibuprofen is a non-steroidal antipyretic, analgesic, and anti-inflammatory drug. Its synthesis process is mainly divided into ketone process, ketal process, rearrangement and hydrolysis process, etc. As the first step reaction in the synthesis chain, the chlorketone process is the most important link in the synthesis chain, and the most critical part of the ketone process is the Friedel-Crafts reaction process. Controlling the Friedel-Crafts reaction is the key to ensuring the quality of ibuprofen products. [0003] At present, there are few researches or reports on the Fuckers reaction of ibuprofen in China, and there are few specific operating parameters. In the prior art, the Friedel-Crafts reaction of ibuprofen is produced in batch mode, that is, the complex solution gener...

Claims

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Application Information

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IPC IPC(8): C07C45/46C07C49/80
CPCC07C45/46C07C49/80
Inventor 杜德平岳金彩谭心顺徐文辉寇祖星郑世清夏丙堃贾健波孙科曾民成
Owner SHANDONG XINHUA PHARMA CO LTD
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