CN102516062A - Hydrolysis outer circulation heat exchange process and device for friedel-crafts reaction liquid for synthesis of ibuprofen - Google Patents
Hydrolysis outer circulation heat exchange process and device for friedel-crafts reaction liquid for synthesis of ibuprofen Download PDFInfo
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- 238000006460 hydrolysis reaction Methods 0.000 title claims abstract description 143
- 230000007062 hydrolysis Effects 0.000 title claims abstract description 142
- 238000005727 Friedel-Crafts reaction Methods 0.000 title claims abstract description 74
- 238000000034 method Methods 0.000 title claims abstract description 62
- 239000012295 chemical reaction liquid Substances 0.000 title claims abstract description 46
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 229960001680 ibuprofen Drugs 0.000 title claims abstract description 20
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 14
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 14
- 230000007797 corrosion Effects 0.000 claims abstract description 19
- 238000005260 corrosion Methods 0.000 claims abstract description 19
- 239000012267 brine Substances 0.000 claims description 50
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 50
- 239000000243 solution Substances 0.000 claims description 42
- 239000000463 material Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- -1 polytetrafluoroethylene Polymers 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910002804 graphite Inorganic materials 0.000 claims description 4
- 239000010439 graphite Substances 0.000 claims description 4
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 4
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 4
- 238000012545 processing Methods 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 11
- 238000012546 transfer Methods 0.000 abstract description 8
- 238000012423 maintenance Methods 0.000 abstract description 5
- 239000007788 liquid Substances 0.000 description 13
- 239000002826 coolant Substances 0.000 description 10
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229910052719 titanium Inorganic materials 0.000 description 4
- 239000010936 titanium Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 239000002221 antipyretic Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- KXUHSQYYJYAXGZ-UHFFFAOYSA-N isobutylbenzene Chemical compound CC(C)CC1=CC=CC=C1 KXUHSQYYJYAXGZ-UHFFFAOYSA-N 0.000 description 2
- 238000013021 overheating Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- GZAIBSUKJNVESM-UHFFFAOYSA-N 2,4-dimethyl-2-phenylpentanal Chemical compound CC(C)CC(C)(C=O)C1=CC=CC=C1 GZAIBSUKJNVESM-UHFFFAOYSA-N 0.000 description 1
- WRJZDDJYWWJLIS-UHFFFAOYSA-N 4-methyl-1-phenylpentan-1-one Chemical compound CC(C)CCC(=O)C1=CC=CC=C1 WRJZDDJYWWJLIS-UHFFFAOYSA-N 0.000 description 1
- 238000003476 Darzens condensation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- VODRWDBLLGYRJT-UHFFFAOYSA-N propan-2-yl 2-chloroacetate Chemical compound CC(C)OC(=O)CCl VODRWDBLLGYRJT-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
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Abstract
Description
技术领域 technical field
本发明属于制药技术领域，具体涉及一种布洛芬合成用傅克反应液水解外循环换热工艺与装置。The invention belongs to the technical field of pharmacy, and in particular relates to a Friedel-Crafts reaction liquid hydrolysis external circulation heat exchange process and device for ibuprofen synthesis.
背景技术 Background technique
布洛芬是目前解热镇痛药三大支柱产品之一，由Nicholson于1964年首先合成，20世纪80年代后期，羧基化法与1，2-转位法工艺的出现使得其生产规模大幅提高。由于布洛芬是一种非甾体消炎药，具有较强的消炎镇痛、解热、抗风湿等疗效，而且毒性低，近几年得到迅速的发展。尽管出现了各种新的布洛芬生产工艺，但是由于收率、设备、三废、安全等条件的限制，目前国内工业上生产布洛芬主要采用缩水甘油酸酯法，即：异丁苯与乙酰氯经过傅克反应制得异丁基苯乙酮，然后与氯乙酸异丙酯进行Darzens缩合，再经过碱水解、酸中和、脱羧反应制得异丁基苯丙醛，然后经氧化或成肟水解制得布洛芬。在该工艺过程中，傅克反应液的水解过程的温度控制较为关键。Ibuprofen is one of the three pillar products of antipyretic and analgesic drugs. It was first synthesized by Nicholson in 1964. In the late 1980s, the appearance of carboxylation and 1,2-transposition technology made its production scale greatly improve. Since ibuprofen is a non-steroidal anti-inflammatory drug, which has strong anti-inflammatory, analgesic, antipyretic, anti-rheumatic effects, and low toxicity, it has been developed rapidly in recent years. Although various new ibuprofen production techniques have occurred, due to the limitations of conditions such as yield, equipment, three wastes, and safety, the current domestic industrial production of ibuprofen mainly adopts the glycidyl ester method, that is: isobutylbenzene and Acetyl chloride is prepared by Friedel-Crafts reaction to produce isobutyl acetophenone, then carries out Darzens condensation with isopropyl chloroacetate, and then undergoes alkali hydrolysis, acid neutralization, and decarboxylation to produce isobutyl phenylpropionaldehyde, and then undergoes oxidation or Into oxime hydrolysis in the system ibuprofen. In this process, the temperature control of the hydrolysis process of the Friedel-Crafts reaction solution is more critical.
现有的傅克反应过程为：将石油醚、三氯化铝按照一定的比例加入到反应罐中，通过搅拌控制温度不超过5℃，在不超温的条件下加入计量的异丁苯，然后加入所需数量的乙酰氯，持续搅拌并反应4小时制得傅克反应液。The existing Friedel-Crafts reaction process is as follows: add petroleum ether and aluminum trichloride into the reaction tank according to a certain ratio, control the temperature by stirring to not exceed 5°C, and add measured isobutylbenzene under the condition of not overheating, Then add the required amount of acetyl chloride, continue to stir and react for 4 hours to obtain Friedel-Crafts reaction solution.
傅克反应液的水解过程为：在水解罐中配置pH＝3的盐酸，将傅克反应液间歇的输送到水解罐中，在保持罐内温度不超过15℃的情况下进行水解3小时左右。水解完毕后，进入下一工序进行水洗。由于温度过高会导致副反应的发生，因此傅克反应液的水解需要在低温条件下完成，但是温度过低，容易产生结晶，导致管道堵塞。工业上水解过程的控制条件为：采用内盘管的换热方式，盘管为钛质材料，盘管内通入低温盐水；低温盐水用量35立方米/小时，水解反应时间为3小时左右，低温盐水进水温度为-17℃，出水温度为-12℃。目前工业上傅克反应液水解时会存在以下几个问题：由于傅克反应液的水解罐采用的是内盘管换热器进行换热，傅克反应液对换热器具有很强的腐蚀性，经常出现内置钛盘管局部因腐蚀而损坏，使傅克反应液与低温盐水混合，从而污染了整个工厂的低温盐水，同时使傅克反应液也遭到污染，产品质量不合格。另一方面，换热器采用的钛管造价昂贵，维修费用很高，频繁更换会给车间造成很大的经济负担，使得生产成本高，降低了经济效益。从传热角度看，内置钛盘管的换热方式的传热效率较低，限制了水解过程生产能力的提高。The hydrolysis process of the Friedel-Crafts reaction solution is as follows: configure hydrochloric acid with pH=3 in the hydrolysis tank, transport the Friedel-Crafts reaction solution to the hydrolysis tank intermittently, and carry out hydrolysis for about 3 hours while keeping the temperature in the tank not exceeding 15°C . After the hydrolysis is completed, enter the next process for water washing. Because the temperature is too high will lead to the occurrence of side reactions, so the hydrolysis of the Friedel-Crafts reaction solution needs to be completed at low temperature, but the temperature is too low, crystallization is easy to occur, resulting in pipeline blockage. The control conditions of the hydrolysis process in the industry are: the heat exchange method of the inner coil is adopted, the coil is made of titanium material, and low-temperature brine is passed into the coil; the amount of low-temperature brine is 35 cubic meters per hour, and the hydrolysis reaction time is about 3 hours. The brine inlet temperature is -17°C, and the outlet water temperature is -12°C. At present, the following problems exist in the hydrolysis of the Friedel-Crafts reaction solution in industry: Since the hydrolysis tank of the Friedel-Crafts reaction solution uses an inner coil heat exchanger for heat exchange, the Friedel-Crafts reaction solution has strong corrosion on the heat exchanger The built-in titanium coil is often partially damaged due to corrosion, causing the Friedel-Crafts reaction solution to mix with low-temperature brine, thereby polluting the low-temperature brine of the entire factory, and the Friedel-Crafts reaction solution is also polluted, resulting in unqualified product quality. On the other hand, the titanium tube used in the heat exchanger is expensive, and the maintenance cost is very high. Frequent replacement will cause a great economic burden on the workshop, resulting in high production costs and reduced economic benefits. From the perspective of heat transfer, the heat transfer efficiency of the heat transfer method with built-in titanium coil is low, which limits the improvement of the production capacity of the hydrolysis process.
发明内容 Contents of the invention
本发明克服了现有技术的不足，提出了布洛芬合成用傅克反应液水解外循环换热工艺与装置，所述工艺流程采用外循环式换热工艺控制傅克反应液水解过程中的温度，实现傅克反应液顺利完成水解过程，稳定控制水解过程的反应温度，提高传热效率，降低设备的维护费用，避免腐蚀泄露造成的产品不合格的问题。The present invention overcomes the deficiencies in the prior art, and proposes a Friedel-Crafts reaction liquid hydrolysis external circulation heat exchange process and device for ibuprofen synthesis, and the process flow adopts an external circulation heat exchange process to control the Friedel-Crafts reaction liquid hydrolysis process. Temperature, realize the smooth completion of the hydrolysis process of the Friedel-Crafts reaction solution, stably control the reaction temperature of the hydrolysis process, improve heat transfer efficiency, reduce equipment maintenance costs, and avoid product substandard problems caused by corrosion leakage.
本发明的技术方案为：一种布洛芬合成用傅克反应液水解外循环换热装置，包括中央控制单元、水解罐、换热器组合、循环泵，在所述水解罐的上部设有控制装置和进料入口，所述水解罐的内部设有搅拌装置，所述水解罐的底部设有反应液出口，所述中央控制单元通过信号线与控制装置相连接，所述中央控制单元通过信号线分别与换热器组合和循环泵相连接，所述水解罐的反应液出口通过管道与循环泵相连，所述换热器组合为通过管道串联在一起的两个换热器，所述换热器组合通过管道与循环泵相连，所述水解罐的反应液入口通过管道与换热器组合相连。The technical scheme of the present invention is: a kind of Friedel-Crafts reaction solution hydrolysis external circulation heat exchange device for ibuprofen synthesis, comprising a central control unit, a hydrolysis tank, a heat exchanger combination, and a circulating pump, and the upper part of the hydrolysis tank is provided with control device and feed inlet, the interior of the hydrolysis tank is provided with a stirring device, the bottom of the hydrolysis tank is provided with a reaction liquid outlet, the central control unit is connected with the control device through a signal line, and the central control unit is connected to the control device through The signal lines are respectively connected to the heat exchanger combination and the circulation pump, the reaction liquid outlet of the hydrolysis tank is connected to the circulation pump through a pipeline, and the heat exchanger combination is two heat exchangers connected in series through pipelines, and the The heat exchanger combination is connected with the circulation pump through the pipeline, and the reaction liquid inlet of the hydrolysis tank is connected with the heat exchanger combination through the pipeline.
换热器组合设有换热器入口传感器模块和换热器出口传感器模块，所述换热器为石墨或聚四氟乙烯等耐腐蚀的材料，其形式为列管式换热器。The heat exchanger assembly is provided with a heat exchanger inlet sensor module and a heat exchanger outlet sensor module, and the heat exchanger is made of corrosion-resistant materials such as graphite or polytetrafluoroethylene, and is in the form of a tube-and-tube heat exchanger.
在所述水解罐的底部侧面设有水解罐传感器模块。A hydrolysis tank sensor module is arranged on the bottom side of the hydrolysis tank.
一种布洛芬合成用傅克反应液水解外循环换热工艺，利用水解罐、换热器、循环泵设备进行水解，具体水解工艺流程为：A kind of Friedel-Crafts reaction solution hydrolysis external circulation heat transfer process for ibuprofen synthesis, utilizing hydrolysis tank, heat exchanger, circulation pump equipment to carry out hydrolysis, specific hydrolysis process flow is:
1)在水解罐中配置pH＝3的盐酸作为水解液；1) Hydrochloric acid of pH=3 is configured in the hydrolysis tank as the hydrolyzate;
2)打开换热器的低温盐水(冷公用工程)的进口阀门与出口阀门；2) Open the inlet valve and outlet valve of the low-temperature brine (cold utility) of the heat exchanger;
3)启动循环泵进行水解液的降温，低温盐水的进口温度为-17℃～-5℃，低温盐水的出口温度为-12℃～0℃；3) Start the circulation pump to cool down the hydrolyzate, the inlet temperature of the low-temperature brine is -17°C to -5°C, and the outlet temperature of the low-temperature brine is -12°C to 0°C;
4)将傅克反应液连续输送到水解罐中，在控制系统的控制下保持罐内温度0～10℃；4) Continuously transport the Friedel-Crafts reaction solution to the hydrolysis tank, and keep the temperature in the tank at 0-10°C under the control of the control system;
5)重复步骤4，进行水解1～3小时；5) Repeat step 4 to carry out hydrolysis for 1 to 3 hours;
6)关闭循环泵，关闭换热器的低温盐水进口阀门与出口阀门，水解完毕，完成液进入下一工序进行水洗。6) Turn off the circulating pump, close the low-temperature brine inlet valve and outlet valve of the heat exchanger, and after the hydrolysis is completed, the finished liquid enters the next process for water washing.
针对第四步，傅克反应液采用连续进料方式，避免间歇进料造成反应液温度波动以及水解罐内局部物料温度过高。For the fourth step, the Friedel-Crafts reaction solution adopts a continuous feeding method to avoid temperature fluctuations of the reaction solution caused by intermittent feeding and excessive temperature of local materials in the hydrolysis tank.
针对第五步，保持低温盐水的进口温度为-17℃～-5℃，低温盐水的出口温度为-12℃～0℃，流量为5吨/小时～70吨/小时。For the fifth step, keep the inlet temperature of the low-temperature brine at -17°C to -5°C, the outlet temperature of the low-temperature brine at -12°C to 0°C, and the flow rate at 5 tons/hour to 70 tons/hour.
针对第五步，经过换热器组成的外循环冷却后，返回到水解罐的温度控制在5℃～10℃，傅克反应液的外循环量为10吨/小时～90吨/小时。For the fifth step, after being cooled by the external circulation composed of heat exchangers, the temperature returned to the hydrolysis tank is controlled at 5°C to 10°C, and the external circulation volume of the Friedel-Crafts reaction solution is 10 tons/hour to 90 tons/hour.
针对第六步，对傅克反应液的处理能力为0.5吨/小时～5吨/小时，操作时间为1小时～4小时。For the sixth step, the processing capacity of the Friedel-Crafts reaction liquid is 0.5 ton/hour to 5 ton/hour, and the operation time is 1 hour to 4 hours.
本发明的原理为：Principle of the present invention is:
傅克反应液的水解是一个放热反应，水解过程中放出的热量通过外循环换热器E01和E02移出反应体系，通过控制低温盐水的流量与傅克反应液的进料流量，控制傅克反应液水解过程中的温度在所规定的范围内。低温水的流量与入口温度对工艺过程的运行有着非常明显的影响，在使用过程中，如果低温盐水的流量增大，则水解液的出口温度降低，很容易导致低于水解液的结晶点，从而造成换热器堵塞；如果低温盐水的流量减少，则水解液的出口温度增大，很容易导致完不成水解罐的降温任务，使水解罐的内的液体温度升高，副反应增加，从而造成产品质量不合格。同理，低温盐水的入口温度也存在如此的影响。所以，低温盐水的流量与入口温度应该得到严格的控制，本发明对水解液的出口温度进行自动控制，使得水解过程中水解罐内的液体温度稳定在所需的范围。同时为了避免间歇进料产生的水解罐中反应液温度波动和可能产生的局部温度过高从而提高产品质量，本发明采用连续进料方式将傅克反应液输送到水解罐中。为达到控温精确，提高传热效率的目的，换热器选用抗低温、耐腐蚀的石墨与聚四氟乙烯等材质。The hydrolysis of the Friedel-Crafts reaction solution is an exothermic reaction. The heat released during the hydrolysis process is removed from the reaction system through the external circulation heat exchangers E01 and E02. The temperature during the hydrolysis of the reaction solution is within the specified range. The flow rate and inlet temperature of low-temperature water have a very obvious impact on the operation of the process. During use, if the flow rate of low-temperature brine increases, the outlet temperature of the hydrolyzate will decrease, which will easily lead to a drop below the crystallization point of the hydrolyzate. As a result, the heat exchanger is blocked; if the flow rate of the low-temperature brine decreases, the outlet temperature of the hydrolyzate increases, which can easily lead to the inability to complete the task of cooling the hydrolysis tank, increasing the temperature of the liquid in the hydrolysis tank and increasing the side reactions, thereby resulting in unqualified product quality. In the same way, the inlet temperature of low-temperature brine also has such an influence. Therefore, the flow rate and inlet temperature of the low-temperature brine should be strictly controlled. The present invention automatically controls the outlet temperature of the hydrolyzed liquid so that the temperature of the liquid in the hydrolyzed tank is stabilized within the required range during the hydrolysis process. Simultaneously, in order to avoid the temperature fluctuation of the reaction solution in the hydrolysis tank caused by intermittent feeding and the possible local overheating so as to improve product quality, the present invention adopts a continuous feeding method to transport the Friedel-Crafts reaction solution to the hydrolysis tank. In order to achieve precise temperature control and improve heat transfer efficiency, the heat exchanger is made of graphite and polytetrafluoroethylene, which are resistant to low temperature and corrosion.
本发明具有如下有益效果：The present invention has following beneficial effects:
1)本发明所述工艺流程采用外循环式换热工艺控制傅克反应液水解过程中的温度，实现傅克反应液顺利完成水解过程，稳定控制水解过程的反应温度，提高传热效率，降低设备的维护费用，避免腐蚀泄露造成的产品不合格的问题。1) The technological process of the present invention adopts an external circulation heat exchange process to control the temperature in the hydrolysis process of the Friedel-Crafts reaction solution, realizes the successful completion of the hydrolysis process of the Friedel-Crafts reaction solution, stably controls the reaction temperature of the hydrolysis process, improves heat transfer efficiency, and reduces The maintenance cost of equipment can avoid the problem of product substandard caused by corrosion leakage.
2)本发明能够稳定运行，不会出现腐蚀泄露造成的产品不合格或者设备频繁维修造成的成本很高的问题。2) The present invention can run stably without the problem of unqualified products caused by corrosion leakage or high cost caused by frequent maintenance of equipment.
3)本发明在处理相同的傅克反应液时所需要的操作时间减少，劳动效率提高。3) The present invention reduces the operating time required when processing the same Friedel-Crafts reaction solution, and improves labor efficiency.
4)本发明的傅克反应液采用连续进料方式，避免间歇进料造成反应液温度波动以及水解罐内局部物料温度过高，减少了副反应的发生，有利于提高产品的纯度。4) The Friedel-Crafts reaction solution of the present invention adopts a continuous feeding method, which avoids temperature fluctuations of the reaction solution caused by intermittent feeding and excessive temperature of local materials in the hydrolysis tank, reduces the occurrence of side reactions, and is conducive to improving the purity of the product.
附图说明 Description of drawings
附图为本发明的结构示意图。Accompanying drawing is the structural representation of the present invention.
图中，1、中央控制单元；2、换热器组合；3、循环泵；4、换热器出口传感器模块；5、水解罐；6、控制装置；7、搅拌装置；8、水解罐传感器模块；9、进料入口；10、反应液出口；11、反应液入口；12、换热器入口传感器模块。In the figure, 1. Central control unit; 2. Heat exchanger combination; 3. Circulating pump; 4. Heat exchanger outlet sensor module; 5. Hydrolysis tank; 6. Control device; 7. Stirring device; 8. Hydrolysis tank sensor module; 9, feed inlet; 10, reaction liquid outlet; 11, reaction liquid inlet; 12, heat exchanger inlet sensor module.
具体实施方式 Detailed ways
一种布洛芬合成用傅克反应液水解外循环换热装置，包括中央控制单元1、水解罐5、换热器组合2、循环泵3，在所述水解罐5的上部设有控制装置6和进料入口9，所述水解罐5的内部设有搅拌装置7，所述水解罐5的底部设有反应液出口10，所述中央控制单元1通过信号线与控制装置6相连接，所述中央控制单元1通过信号线分别与换热器组合2和循环泵3相连接，所述水解罐5的反应液出口10通过管道与循环泵3相连，所述换热器组合2为通过管道串联在一起的两个换热器，所述换热器组合2通过管道与循环泵3相连，所述水解罐5的反应液入口11通过管道与换热器组合2相连。换热器组合2设有换热器入口传感器模块12和换热器出口传感器模块4，所述换热器为石墨或聚四氟乙烯等耐腐蚀的材料，其形式为列管式换热器。在所述水解罐5的底部侧面设有水解罐传感器模块8。中央控制单元1通过信号线与换热器组合2相连接，水解罐5的控制装置6与搅拌装置7通过机械机构相连接，中央控制单元1可控制水解罐5的控制装置，中央控制单元1通过信号线可控制循环泵3和换热器组合2。换热器出口传感器模块4包括压力传感器、温度传感器和流量传感器。水解罐传感器模块8包括压力传感器、温度传感器和流量传感器。换热器入口传感器模块12包括压力传感器、温度传感器和流量传感器。A Friedel-Crafts reaction liquid hydrolysis external circulation heat exchange device for ibuprofen synthesis, comprising a central control unit 1, a
首先在水解罐内加入一定量的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，换热器的冷却介质为低温盐水。水解罐内的水解液冷却到0℃～10℃范围之后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。First, a certain amount of hydrolyzate is added to the hydrolysis tank, and then the circulating pump is started to circulate and cool the hydrolyzate through an external heat exchanger. The cooling medium of the heat exchanger is low-temperature brine. After the hydrolyzate in the hydrolysis tank is cooled to the range of 0°C to 10°C, the Friedel-Crafts reaction liquid feed valve is opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process.
以下是本发明的实施实例：The following are implementation examples of the present invention:
实施实例1：首先在水解罐内加入1.5吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为45吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-17℃，出口温度为-12℃，流量为20吨/小时。水解罐内的水解液冷却到5℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在2小时内完成，所处理的傅克反应液的总量为2吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation example 1: first add 1.5 tons of hydrolyzate in the hydrolysis tank, then start the circulating pump to circulate and cool the hydrolyzate through an external heat exchanger, and the flow rate of the circulating liquid is 45 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -17°C, the outlet temperature is -12°C, and the flow rate is 20 tons/hour. After the hydrolyzate in the hydrolysis tank was cooled to 5°C, the Friedel-Crafts reaction liquid feed valve was opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 2 hours, and the total amount of Friedel-Crafts reaction liquid treated is 2 tons. The device operates stably without corrosion, leakage, blockage and other problems.
实施实例2：首先在水解罐内加入3吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为55吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-12℃，出口温度为-6℃，流量为20吨/小时。水解罐内的水解液冷却到8℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在3小时内完成，所处理的傅克反应液的总量为4吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation example 2: first add 3 tons of hydrolyzate in the hydrolysis tank, then start the circulating pump to circulate and cool the hydrolyzate through the external heat exchanger, and the flow rate of the circulating liquid is 55 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -12°C, the outlet temperature is -6°C, and the flow rate is 20 tons/hour. After the hydrolyzate in the hydrolysis tank was cooled to 8°C, the Friedel-Crafts reaction solution feed valve was opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 3 hours, and the total amount of Friedel-Crafts reaction liquid processed is 4 tons. The device operates stably without corrosion, leakage, blockage and other problems.
实施实例3：首先在水解罐内加入0.5吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为30吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-10℃，出口温度为-5℃，流量为12吨/小时。水解罐内的水解液冷却到2℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在1小时内完成，所处理的傅克反应液的总量为0.7吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation example 3: first add 0.5 tons of hydrolyzate in the hydrolysis tank, then start the circulating pump to circulate the hydrolyzate through an external heat exchanger for cooling, and the flow rate of the circulating liquid is 30 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -10°C, the outlet temperature is -5°C, and the flow rate is 12 tons/hour. After the hydrolyzate in the hydrolysis tank was cooled to 2°C, the Friedel-Crafts reaction liquid feed valve was opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 1 hour, and the total amount of Friedel-Crafts reaction liquid treated is 0.7 tons. The device operates stably without corrosion, leakage, blockage and other problems.
实施实例4：首先在水解罐内加入1吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为55吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-10℃，出口温度为-5℃，流量为20吨/小时。水解罐内的水解液冷却到0℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在1.5小时内完成，所处理的傅克反应液的总量为1.3吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation example 4: first add 1 ton of hydrolyzate in the hydrolysis tank, then start the circulating pump to circulate and cool the hydrolyzate through the external heat exchanger, and the flow rate of the circulating liquid is 55 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -10°C, the outlet temperature is -5°C, and the flow rate is 20 tons/hour. After the hydrolyzate in the hydrolysis tank is cooled to 0°C, the Friedel-Crafts reaction liquid feeding valve is opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 1.5 hours, and the total amount of Friedel-Crafts reaction liquid treated is 1.3 tons. The device operates stably without corrosion, leakage, blockage and other problems.
实施实例5：首先在水解罐内加入2.0吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为45吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-17℃，出口温度为-12℃，流量为30吨/小时。水解罐内的水解液冷却到6℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在2小时内完成，所处理的傅克反应液的总量为2.7吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation example 5: first add 2.0 tons of hydrolyzate in the hydrolysis tank, then start the circulating pump to circulate and cool the hydrolyzate through an external heat exchanger, and the flow rate of the circulating liquid is 45 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -17°C, the outlet temperature is -12°C, and the flow rate is 30 tons/hour. After the hydrolyzate in the hydrolysis tank was cooled to 6°C, the Friedel-Crafts reaction liquid feed valve was opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 2 hours, and the total amount of Friedel-Crafts reaction liquid treated is 2.7 tons. The device operates stably without corrosion, leakage, blockage and other problems.
实施实例6：首先在水解罐内加入2.5吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为30吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-10℃，出口温度为-5℃，流量为20吨/小时。水解罐内的水解液冷却到5℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在3.5小时内完成，所处理的傅克反应液的总量为3.3吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation example 6: first add 2.5 tons of hydrolyzate in the hydrolysis tank, then start the circulating pump to circulate and cool the hydrolyzate through an external heat exchanger, and the flow rate of the circulating liquid is 30 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -10°C, the outlet temperature is -5°C, and the flow rate is 20 tons/hour. After the hydrolyzate in the hydrolysis tank was cooled to 5°C, the Friedel-Crafts reaction liquid feed valve was opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 3.5 hours, and the total amount of Friedel-Crafts reaction liquid treated is 3.3 tons. The device operates stably without corrosion, leakage, blockage and other problems.
实施实例7：首先在水解罐内加入3.8吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为65吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-9℃，出口温度为-4℃，流量为40吨/小时。水解罐内的水解液冷却到4℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在2.5小时内完成，所处理的傅克反应液的总量为5吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation Example 7: First add 3.8 tons of hydrolyzate in the hydrolysis tank, then start the circulation pump to circulate the hydrolyzate through an external heat exchanger for cooling, and the flow rate of the circulation liquid is 65 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -9°C, the outlet temperature is -4°C, and the flow rate is 40 tons/hour. After the hydrolyzate in the hydrolysis tank was cooled to 4°C, the Friedel-Crafts reaction liquid feed valve was opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 2.5 hours, and the total amount of Friedel-Crafts reaction liquid processed is 5 tons. The device operates stably without corrosion, leakage, blockage and other problems.
实施实例8：首先在水解罐内加入4.5吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为70吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-17℃，出口温度为-12℃，流量为60吨/小时。水解罐内的水解液冷却到1℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在2小时内完成，所处理的傅克反应液的总量为6吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation Example 8: First add 4.5 tons of hydrolyzate to the hydrolysis tank, then start the circulation pump to circulate and cool the hydrolyzate through an external heat exchanger, and the flow rate of the circulation liquid is 70 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -17°C, the outlet temperature is -12°C, and the flow rate is 60 tons/hour. After the hydrolyzate in the hydrolysis tank was cooled to 1°C, the Friedel-Crafts reaction liquid feed valve was opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 2 hours, and the total amount of Friedel-Crafts reaction liquid treated is 6 tons. The device operates stably without corrosion, leakage, blockage and other problems.
实施实例9：首先在水解罐内加入6.0吨的水解液，然后启动循环泵将水解液通过外置换热器进行循环冷却，循环液的流量为45吨/小时。换热器的冷却介质为低温盐水，低温盐水的入口温度为-15℃，出口温度为-10℃，流量为60吨/小时。水解罐内的水解液冷却到0℃后，开启傅克反应液进料阀进行连续进料。通过控制低温盐水的流量以及傅克反应液的进料速度，使整个水解过程中水解罐的温度稳定在0℃～10℃。整个水解过程在3小时内完成，所处理的傅克反应液的总量为8吨。装置稳定运行，无腐蚀、泄露、堵塞等问题出现。Implementation Example 9: First add 6.0 tons of hydrolyzate to the hydrolysis tank, then start the circulating pump to circulate and cool the hydrolyzate through an external heat exchanger, and the flow rate of the circulating liquid is 45 tons/hour. The cooling medium of the heat exchanger is low-temperature brine, the inlet temperature of the low-temperature brine is -15°C, the outlet temperature is -10°C, and the flow rate is 60 tons/hour. After the hydrolyzate in the hydrolysis tank is cooled to 0°C, the Friedel-Crafts reaction liquid feeding valve is opened for continuous feeding. By controlling the flow rate of the low-temperature brine and the feed rate of the Friedel-Crafts reaction solution, the temperature of the hydrolysis tank is stabilized at 0° C. to 10° C. during the entire hydrolysis process. The whole hydrolysis process is completed within 3 hours, and the total amount of Friedel-Crafts reaction liquid processed is 8 tons. The device operates stably without corrosion, leakage, blockage and other problems.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103880622A (en) * | 2012-12-19 | 2014-06-25 | 山东新华制药股份有限公司 | Ibuprofen production device and technology |
| CN112882513A (en) * | 2021-01-15 | 2021-06-01 | 青岛科技大学 | Precise temperature control device and method suitable for ibuprofen Friedel-crafts reaction |
| CN114085135A (en) * | 2021-10-29 | 2022-02-25 | 山东新华制药股份有限公司 | Continuous production method suitable for ibuprofen Friedel-crafts reaction |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1706802A (en) * | 2005-05-27 | 2005-12-14 | 中国科学院上海有机化学研究所 | A method for preparing 2-aryl lactate, naproxen and ibuprofen |
| CN101456808A (en) * | 2009-01-06 | 2009-06-17 | 长沙理工大学 | Method for preparing ibuprofen |
-
2011
- 2011-12-02 CN CN201110399029.8A patent/CN102516062B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1706802A (en) * | 2005-05-27 | 2005-12-14 | 中国科学院上海有机化学研究所 | A method for preparing 2-aryl lactate, naproxen and ibuprofen |
| CN101456808A (en) * | 2009-01-06 | 2009-06-17 | 长沙理工大学 | Method for preparing ibuprofen |
Non-Patent Citations (1)
| Title |
|---|
| 刘志雄，程清蓉: "酮基布洛芬生产工艺研究与改进", 《化学试剂》, vol. 31, no. 12, 31 December 2009 (2009-12-31) * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103880622A (en) * | 2012-12-19 | 2014-06-25 | 山东新华制药股份有限公司 | Ibuprofen production device and technology |
| CN103880622B (en) * | 2012-12-19 | 2016-08-17 | 山东新华制药股份有限公司 | A kind of brufen process units and technique |
| CN112882513A (en) * | 2021-01-15 | 2021-06-01 | 青岛科技大学 | Precise temperature control device and method suitable for ibuprofen Friedel-crafts reaction |
| CN114085135A (en) * | 2021-10-29 | 2022-02-25 | 山东新华制药股份有限公司 | Continuous production method suitable for ibuprofen Friedel-crafts reaction |
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